= 0.988. Benefits of multiplexed
assays compared to ELISAs and CF tests include reduced serum sample volumes
needed for analysis, less labor, and shorter assay time.
PMID- 28685647
TI - Effects of a phase change cooling garment during exercise in the heat.
AB - The purpose of our study was to examine the physiological, perceptual, and
performance effects of wearing a phase change cooling garment (CG) during an
interval exercise routine in the heat. Sixteen male participants (age 23 +/- 3
years, ht 1.76 +/- 0.11 m; wt 78.5 +/- 11.2 kg; body fat 15.2 +/- 5.8%) completed
two trials (one with phase change inserts, CG, and one control without inserts)
consisting of two submaximal exercise portions separated by 5-minute seated rest,
and a final maximal effort performance bout. Each submaximal bout involved 30
seconds or 1 minute of muscular endurance and agility exercises and 5 minutes of
treadmill jogging and step-ups. The performance bout included 30 seconds or 1
minute of muscular endurance and agility exercises, with participants completing
as many repetitions as possible, followed by a 15-minute recovery (active and
passive). Rectal temperature (Tre) and heart rate were not different between
trials, however change in Tre from baseline was improved during 10 and 15 minutes
of recovery with the CG (P < .05). Mean skin temperature was lower using the CG
vs control throughout the trial (P < .05). Thermal sensation was lower when using
the CG compared to control (P < .001). There were no differences in any outcomes
of the performance exercises (P > .05). These findings indicate that the
continuous use of a CG during an interval style workout in the heat provides
improvements in thermal sensation, however, only minimal thermophysiological
benefits, and no performance augmentation.
PMID- 28685649
TI - Misdiagnosis: CNS Erdheim-Chester disease mimicking CLIPPERS.
AB - Introduction Chronic lymphocytic inflammation with pontine perivascular
enhancement responsive to steroids (CLIPPERS) is an inflammatory central nervous
system (CNS) disorder with particular involvement of the pons. Diagnostic
criteria include a range of clinical symptoms related to the underlying brainstem
pathology, visible with magnetic resonance imaging (MRI). MRI findings include
the appearance of punctuate and curvilinear gadolinium enhancement 'peppering'
the pons. We discuss a patient presenting with clinical and radiographic
characteristics of CLIPPERS who was diagnosed with Erdheim-Chester disease (ECD).
Case report A 52-year-old male presented with 2 years of progressive spasticity,
dysarthria, and gait instability. Initially, he was diagnosed with Parkinson's
disease at an outside hospital, based on tremor, rigidity, and gait instability;
however, he failed to improve with a trial of levodopa. Brain MRI showed small
enhancing parenchymal nodules coalescing in the central pons, but also affecting
the cerebellum and cerebellar peduncles, with more punctate enhancing lesions in
the cerebral lobar subcortical white matter. When the patient's response to
steroids was inadequate, further imaging was done, revealing perinephric
processes. Subsequent biopsy revealed ECD. Conclusions A review of the literature
for cases of CLIPPERS demonstrated a subset of patients later found to have
various malignancies involving the CNS. This case report uses the patient's
unique radiographic and clinical presentation to demonstrate the importance of
the exclusion criteria within the CLIPPERS diagnostic requirements and stresses
red flags suggestive of alternative diagnoses. This distinction is of high
importance when differentiating a relatively benign process such as CLIPPERS from
more malignant diseases.
PMID- 28685650
TI - An unusual cause of left main coronary artery obstruction.
PMID- 28685651
TI - Successful Transfer of a Motor Learning Strategy to a Novel Sport.
AB - This study investigated whether secondary school students who were taught a motor
learning strategy could transfer their knowledge of the strategy to learning a
novel task. Twenty adolescents were randomly allocated to a strategy or control
group. The strategy group was taught Singer's five-step learning strategy, while
the control group received information on the evolution and biomechanics of the
basketball free throw. Both groups received three 1-hour practice sessions on a
modified basketball shooting task. After one month, participants were introduced
to the transfer task, golf putting. Performance accuracy was recorded for all
tasks, and participants completed questionnaires regarding strategy use during
practice. Participants taught the five-step learning strategy successfully
recalled and applied it after a 1-month interval, and they demonstrated superior
performance on both acquisition and transfer tasks, relative to the control
group. Physical education teachers and coaches should consider using this
learning strategy to enhance the learning of closed motor skills.
PMID- 28685652
TI - The Ubiquitous Pharmacogenomics consortium: making effective treatment
optimization accessible to every European citizen.
PMID- 28685653
TI - Impact of statin therapy on all-cause mortality and ICD interventions in heart
failure patients - a systematic review.
AB - OBJECTIVES: Implantable cardioverter defibrillators (ICDs) have a unique role for
the primary and secondary prevention of sudden cardiac death (SCD). The aim of
our systematic review is to present the existing data about the impact of statins
on all-cause mortality and ICD interventions in heart failure (HF) patients who
had an ICD implanted either for primary or for secondary prevention of SCD.
METHODS AND RESULTS: We searched PubMed database and the reference list of the
relevant studies for retrieving studies evaluating the effect of statins on all
cause mortality and ICD interventions in HF patients. We finally included 17
relevant studies in our systematic review. Of them, nine studies included data
about the impact of statins on all-cause mortality, eight studies about the
impact of statins on appropriate ICD interventions and three studies about the
impact of statins on inappropriate ICD interventions in HF patients. These data
showed that statins seem to have a beneficial role in the reduction of all-cause
mortality and ICD interventions in HF patients. CONCLUSIONS: Statins seem to have
a beneficial role in the reduction of all-cause mortality and ICD interventions
in HF patients. However, further research about pleiotropic effects of statins is
needed as well randomized control trials to elucidate the exact role of statin
therapy in ICD outcomes.
PMID- 28685656
TI - A combined technique using a muscular flap and endobronchial stent to repair
complex broncho-oesophageal fistulae supported by ECMO.
AB - INTRODUCTION: Certain broncho-oesophageal fistulae require surgical repair.
Herein, we describe an innovative surgical technique combining intercostal flap
and endobronchial stenting. CASE REPORTS: Two patients, each with a with complex
broncho-oesophageal fistula 2 years after radio-chemotherapy, were hospitalised
for severe respiratory infection and extension of the fistula despite previous
endoscopic treatment. The first patient presented with respiratory distress
(ARDS). She had emergency surgery under extra corporeal membrane oxygenation:
oesophagectomy and reconstruction of the left bronchus by a vascularised
intercostal flap. Stenting was performed on day 10, due to persistence of the
fistula. At 3 months the bronchus was healed, but the patient died of cerebral
bleeding. For the second patient, repair was proposed before severe ARDS with the
same surgical and ventilatory strategy and a stent was preventively inserted
after surgery. After 3 months, the stent was removed and the left bronchus was
healed. CONCLUSIONS: Complex post-radiotherapy broncho-oesophageal fistulae
should be treated surgically before respiratory complications arise, by combining
reconstruction with a vascularised flap and transient stenting.
PMID- 28685657
TI - Introducing ICD-resistant mortality as an end point to evaluate the clinical
efficacy of an implantable cardioverter-defibrillator in ischaemic
cardiomyopathy.
AB - OBJECTIVE: A new end point called ICD-resistant mortality was evaluated to assess
the clinical efficacy of ICD implantations. METHODS AND RESULTS: In 302 ICD
patients with ischaemic cardiomyopathy, we investigated which clinical parameters
predicted useful ICD implantations using cumulative incidence competing risk
analysis. Implantation was deemed clinically useful when the ICD provided
appropriate therapy and the patient survived implantation by 1 year and the first
shock by 30 days. ICD-resistant mortality (ICDRM) was defined as death within 30
days after the first shock, within 1 year of implantation or without previous
appropriate ICD therapy. After 5 years, ICDRM occurred in 23% of implantations,
while 36% were clinically useful. After multivariable analysis, ICDRM was
associated with LVEF <35% (HR: 2.63; p = .005), beta-blocker dose <50% (HR: 2.0;
p = .01) and anterior or diffuse infarct location (HR: 3.61; p = .001 and HR:
2.89; p = .02). Useful ICD implantations were associated with beta-blocker dose
<50% (HR: 1.64; p = .02) and non-anterior infarct location (HR: 3.22 vs anterior
and 1.59 vs diffuse; combined p<.001). CONCLUSIONS: Five years after
implantation, an ICD could be classified as useful in 1 out of 3, while ICDRM
occurred in one out of four patients. At 10 years, up to 80% of implantations
could be categorized. Lower LVEF was related with significantly higher incidence
of ICDRM. Anterior infarcts were associated with more ICDRM and less useful
implantations than non-anterior infarcts. Future risk stratification for ICD
should focus more on the discrimination between arrhythmic risk, probably
preventable by ICDs and ICD-resistant mortality risk.
PMID- 28685658
TI - Narrow QRS tachycardia with RR alternans and QRS alternans: what is the
mechanism?
PMID- 28685659
TI - Electrical storm secondary to cardiac metastasis of non-small cell lung cancer.
PMID- 28685660
TI - Recovery From Substance Abuse Among Zimbabwean Men: An Occupational Transition.
AB - Substance abuse is a rising global problem, associated with medical, psychiatric,
family, occupational, legal, political, financial, and spiritual problems.
Recovery is an important area of consideration in occupational therapy's quest to
promoting health and well-being. This narrative inquiry explored the journey of
recovery from substance abuse among young adult Zimbabwean men. Three men were
purposively selected to participate in in-depth narrative interviews about their
occupations during recovery. Data were analyzed using a narrative analysis.
Explanatory stories and three superordinate themes illustrated how substance
abuse was associated with both positive and negative outcomes. The recovery
process emerged as an ongoing occupational transition, influenced by occupational
identity and involving changes in occupational participation. Recovery from
substance abuse can be conceptualized as an occupational transition. Ongoing
participation in "healthy" and meaningful occupations is key factor in this
process. Construction of a positive occupational identity is also central.
PMID- 28685661
TI - Treatment of infrainguinal arterial thromboembolic acute occlusions with the
Aspirex(r) mechanical thrombectomy device.
AB - OBJECTIVE: In this study, we investigated the safety and effectiveness of the
Aspirex(r) mechanical thrombectomy system for the treatment of acute
infrainguinal arterial thromboembolic occlusions. METHODS: We retrospectively
identified consecutive patients at our clinic with infrainguinal thromboembolic
acute occlusions treated with the Aspirex(r) mechanical thrombectomy device.
Primary end points included technical success, defined as the complete
revascularization of the acutely occluded vessel, and clinical success, defined
as the absence of amputation within 60 d. Secondary end points included 1-year
embolized vessel primary patency. RESULTS: Twenty-four patients with
infrainguinal arterial acute thromboembolic occlusions were treated with the
mechanical thrombectomy system (five infrapopliteal, 12 femoropopliteal and seven
popliteal). Technical success occurred in 18 patients (75%), and clinical success
occurred in 24 (100%). The 1-year embolized vessel primary patency rate was 75%
(n = 18). The 1-year limb salvage rate was 95.8% (n = 23). CONCLUSIONS: The use
of the Aspirex(r) mechanical thrombectomy is effective for the management of
acute thromboembolic occlusions of infrainguinal arteries. Caution is needed when
using it in smaller vessels, particularly distally below the knee.
PMID- 28685662
TI - Simultaneous functional photoacoustic microscopy and electrocorticography reveal
the impact of rtPA on dynamic neurovascular functions after cerebral ischemia.
AB - The advance of thrombolytic therapy has been hampered by the lack of optimization
of the therapy during the hyperacute phase of focal ischemia. Here, we
investigate neurovascular dynamics using a custom-designed hybrid
electrocorticography (ECoG)-functional photoacoustic microscopy (fPAM) imaging
system during the hyperacute phase (first 6 h) of photothrombotic ischemia (PTI)
in male Wistar rats following recombinant tissue plasminogen activator (rtPA)
mediated thrombolysis. We reported, for the first time, the changes in neural
activity and cerebral hemodynamic responses following rtPA infusion at different
time points post PTI. Interestingly, very early administration of rtPA (< 1 h
post PTI) resulted in only partial recovery of neurovascular dynamics
(specifically , neural activity recovered to 71 +/- 3.5% of baseline and
hemodynamics to only 52 +/- 2.6% of baseline) and late administration of rtPA (>
4 h post PTI) resulted in the deterioration of neurovascular function. A
therapeutic window between 1 and 3 h post PTI was found to improve recovery of
neurovascular function (i.e. significant restoration of neural activity to 93 +/-
4.2% of baseline and hemodynamics to 81 +/- 2.1% of baseline, respectively). The
novel combination of fPAM and ECoG enables direct mapping of neurovascular
dynamics and serves as a platform to evaluate potential interventions for stroke.
PMID- 28685663
TI - Arthroscopic treatment of osteochondral lesions of the talus: Nanofracture versus
hyaluronic acid-based cell-free scaffold with concentration of autologous bone
marrow aspirate.
AB - PURPOSE: We aimed to evaluate the early clinical and radiological outcomes of
arthroscopic one-stage treatment with hyaluronic acid-based cell-free scaffold
(HACS) in combination with a concentration of autologous bone marrow aspirate
(CBMA) technique compared to nanofracture (NF). METHODS: A retrospective
evaluation was made of all the patients with focal osteochondral lesions of the
talus that were treated between January 2012 and January 2015. Ninety-eight
patients met the criteria and were enrolled in the study. Forty-six patients
(group 1) were treated with arthroscopic one-stage treatment with CBMA in
combination with an HACS. Fifty-two patients (group 2) were treated with NF.
Patient demographics and cartilage defect characteristics, the AOFAS and VAS
scoring systems were compared between groups. In the evaluation of cartilage
repair tissue, the magnetic resonance observation of cartilage repair tissue
(MOCART) scoring system was used. RESULTS: No significant differences were
determined between the two groups in terms of age ( p = 0.874), body mass index (
p = 0.621), defect size ( p = 0.485), defect depth ( p = 0.674), follow-up time (
p = 0.512). A significant clinical difference was determined between the two
groups according to the AOFAS and VAS scores ( p = 0.028, p = 0.046,
respectively). The mean MOCART score of group 1 was significantly higher ( p =
0.041). CONCLUSIONS: Both NF and HACS with CBMA techniques are beneficial in
treatment of osteochondral lesions of the talus. Better clinical and radiological
results, in addition to higher cartilage quality, could be obtained with HACS
with CBMA technique compared to NF.
PMID- 28685664
TI - Wide resection versus curettage with adjuvant therapy for giant cell tumour of
bone.
PMID- 28685665
TI - Effect of sodium hyaluronate/carboxymethyl cellulose (Guardix-sol) on retear rate
and postoperative stiffness in arthroscopic rotator cuff repair patients: A
prospective cohort study.
AB - PURPOSE: Hyaluronate-based anti-adhesive agents are expected to enhance rotator
cuff healing; however, their effect on the incidence and extent of postoperative
complications such as stiffness and retears has not been investigated. METHODS:
From July 2012 to February 2013, 80 patients undergoing arthroscopic rotator cuff
repair surgery were prospectively enrolled. Forty patients were assigned to the
control group, while the other 40 were assigned to the injection group and
received a Guardix-sol injection immediately after surgery. Passive range of
motion, pain visual analog scale, and functional score were assessed at 8 weeks,
6 months, and 24 months postoperatively. Gliding motion between the deltoid
muscle and the greater tuberosity of the proximal humerus was evaluated using
ultrasonography at 2 and 8 weeks postoperatively, and tendon integrity was
evaluated using magnetic resonance imaging at 6 months postoperatively. RESULTS:
We found no significant difference between the groups regarding gliding motion at
2 weeks postoperatively. However, at 8 weeks, the incidence of poor gliding
motion was 2.5% and 15% for the injected patients and control group,
respectively, which was statistically significant. At 6 months after surgery, the
retear rate between the two groups was not statistically significant. We found no
statistically significant difference between the two groups regarding retear rate
and clinical score throughout the follow-up period. We noted no complications
related to the use of Guardix-sol. CONCLUSIONS: Patients who received the Guardix
sol injection showed improved gliding motion between the deltoid muscle and the
greater tuberosity in the early postoperative period.
PMID- 28685666
TI - MRI findings of lumbar spine instability in degenerative spondylolisthesis.
AB - PURPOSE: To find out the factors suggesting lumbar segmental instability in
patients with degenerative spondylolisthesis (DS) on conventional magnetic
resonance imaging (MRI). METHODS: Ninety-four patients with DS who underwent
decompression surgery with or without fusion were selected. Patient demographics
and findings on simple radiographs and MRI were analyzed. We divided patients
into two groups by the presence of lumbar instability on simple standing plain
radiographs and measured degeneration status of intervertebral discs and facet
joints and distance of facet fluid signal on T2 axial MRI on each groups. The
data were analyzed to find out the correlation between facet fluid signal and
lumbar instability. RESULTS: Sixty-three patients were confirmed to have lumbar
instability (unstable group (UG), 67%), while 31 patients (stable group (SG),
33%) did not have instability on simple radiographs. The mean age was slightly
older in SG ( p < 0.05) and SG patients' degeneration status of intervertebral
discs and facet joints was advanced than UG patients. Fifty-five of 63 patients
had high signal intensity on T2-weighted MR images in the UG, but only 4 of 31
patients had high signal intensity in the SG ( p < 0.001) and UG patients have
more larger facet joint distance than SG patients ( p < 0.001). CONCLUSION: High
signal in facet joints on T2 MR images can be a useful factor suggestive of
lumbar instability. Thus, the identification of fluid signal in the facet joints
on MRI should raise the suspicion for lumbar instability and prompt additional
evaluations such as with stress radiographs.
PMID- 28685667
TI - A variant on promoter of the cannabinoid receptor 1 gene (CNR1) moderates the
effect of valence on working memory.
AB - Cannabinoid receptor 1 gene (CNR1) variants have been related to affective
information processing and, in particular, to stress release. Here, we aimed to
examine whether the endocannabinoid system via CNR1 signaling modulates affective
working memory, the memory system that transiently maintains and manipulates
emotionally charged material. We focused on rs2180619 (A > G) polymorphism and
examined genotype data collected from 231 healthy females. Analyses showed how a
general positivity bias in working memory (i.e., better memory for positive
words) emerged as task strings lengthened only in carriers of the major allele
(AA/AG). Differently, GG carriers showed better memory for affective items in
general (i.e., positive and negative words). These findings are some of the first
to directly highlight the role of variant on promoter of the CNR1 gene in
affective working memory and to evidence a differentiation among CNR1 genotypes
in terms of larger difficulties in disengaging from negative stimuli in GG
carriers.
PMID- 28685668
TI - Investigating the Asymmetrical Roles of Syllabic and Phonemic Awareness in
Akshara Processing.
AB - In this study, we examine the relative contributions of syllabic awareness,
phonemic awareness, and oral vocabulary knowledge in early akshara reading
ability from Grades 1 through 5. The performance of 488 students in two states of
South India, Karnataka (Kannada language) and Andhra Pradesh (Telugu language),
was measured. Results from a commonality analysis indicate that there was an
increasing independent contribution of syllabic awareness to Kannada and Telugu
decoding through the five grades, but the unique contribution of phonemic
awareness steadily declined through the five grades, as it became subsumed within
syllabic awareness. The contribution of oral vocabulary knowledge did not present
a clear pattern across the five grades. This study builds on a growing body of
literature on the akshara orthographies to shed light on the precise nature of
the developmental asymmetry in the dual syllabic and phonemic representation in
akshara reading.
PMID- 28685669
TI - Understanding how domestic health policy is integrated into foreign policy in
South Africa: a case for accelerating access to antiretroviral medicines.
AB - BACKGROUND: South Africa, as an emerging middle-income country, is becoming
increasingly influential in global health diplomacy (GHD). However, little
empirical research has been conducted to inform arguments for the integration of
domestic health into foreign policy by state and non-state actors. This study
seeks to address this knowledge gap. It takes the form of an empirical case study
which analyses how South Africa integrates domestic health into its foreign
policy, using the lens of access to antiretroviral (ARV) medicines. OBJECTIVE: To
explore state and non-state actors' perceptions regarding how domestic health
policy is integrated into foreign policy. The ultimate goal of this study was to
achieve better insights into the health and foreign policy processes at the
national level. METHODS: Employing qualitative approaches, we examined changes in
the South African and global AIDS policy environment. Purposive sampling was used
to select key informants, a sample of state and non-state actors who participated
in in-depth interviews. Secondary data were collected through a systematic
literature review of documents retrieved from five electronic databases,
including review of key policy documents. Qualitative data were analysed for
content. This content was coded, and the codes were collated into tentative
categories and sub-categories using Atlas.ti v.7 software. RESULTS: The findings
of this work illustrate the interplay among social, political, economic and
institutional conditions in determining the success of this integration process.
Our study shows that a series of national and external developments,
stakeholders, and advocacy efforts and collaboration created these integrative
processes. South Africa's domestic HIV/AIDS constituencies, in partnership with
the global advocacy movement, catalysed the mobilization of support for universal
access to ARV treatment nationally and globally, and the promotion of access to
healthcare as a human right. CONCLUSIONS: Transnational networks may influence
government's decision making by providing information and moving issues up the
agenda.
PMID- 28685670
TI - Milk Donor Blood Screening for HIV, Syphilis and Hepatitis B Markers in a
Brazilian Human Milk Bank: Prevalence Time-trends Over the 2005- 2015 Period.
AB - BACKGROUND: Human milk banking has been promoted to provide donated breast milk
for at-risk children whose mothers cannot breastfeed them but this effort was
hindered by the advent of HIV epidemic. OBJECTIVE: To estimate the seroprevalence
of HIV, syphilis and hepatitis B in the blood of human milk donors registered in
a major maternity hospital in the northern region of the Santa Catarina State,
Brazil. METHODS: A retrospective study included serological tests for HIV,
syphilis and hepatitis B screening of milk donor candidates in the 2005-2015
period. The 95% confidence intervals were calculated using the Poisson
distribution. RESULTS: For HIV, the prevalence per 100.000 pregnant women was
155, 170 and zero over the three periods analyzed (2005-2009, 2010-2012 and 2013
2015), respectively. Syphilis prevalence per 100,000 pregnant women was 509, 460
and 1749 in the three periods analyzed. For the HBsAg marker of recent hepatitis
B infection, the prevalence on the same scale was 254, 231 and 299, respectively,
while the anti-HBc prevalence, a marker of lifetime risk for hepatitis B
infection, was 7339 in the 2010-2012 period and 3874 in the 2013-2015 period.
CONCLUSION: High prevalence of HIV, syphilis and hepatitis B was found for the
2005-2015 period among breastfeeding mothers who offered to donate their
exceeding milk to a human milk bank in Brazil. Despite apparent elimination of
the HIV by the end of the period, the decline was not statistically significant.
There was no significant change in the acute hepatitis B prevalence over time but
the increased syphilis prevalence in the most recent period was statistically
significant.
PMID- 28685671
TI - Experimental Models for Aging and their Potential for Novel Drug Discovery.
AB - BACKGROUND: An interesting area of scientific research is the development of
potential antiaging drugs. In order to pursue this goal, it is necessary to
gather the specific knowledge about the adequate preclinical models that are
available to evaluate the beneficial effects of new potential drugs. This review
is focused on invertebrate and vertebrate preclinical models used to evaluate the
efficacy of antiaging compounds, with the objective to extend life span and
health span. METHODS: Research and online content related to aging, antiaging
drugs, experimental aging models is reviewed. Moreover, in this review, the main
experimental preclinical models of organisms that have contributed to the
research in the pharmacology of lifespan extension and the understanding of the
aging process are discussed. RESULTS: Dietary restriction (DR) constitutes a
common experimental process to extend life span in all organisms. Besides,
classical antiaging drugs such as resveratrol, rapamycin and metformin
denominated as DR mimetics are also discussed. Likewise, the main therapeutic
targets of these drugs include sirtuins, IGF-1, and mTOR, all of them being
modulated by DR. CONCLUSION: Advances in molecular biology have uncovered the
potential molecular pathways involved in the aging process. Due to their
characteristics, invertebrate models are mainly used for drug screening. The
National Institute on Aging (NIA) developed the Interventions Testing Program
(ITP). At the preclinical level, the ITP uses Heterogeneous mouse model (HET)
which is probably the most suitable rodent model to study potential drugs against
aging prevention. The accelerated-senescence mouse P8 is also a mammalian rodent
model for aging research. However, when evaluating the effect of drugs on a
preclinical level, the evaluation must be done in non-human primates since it is
the mammalian specie closest to humans. Research is needed to investigate the
impact of new potential drugs for the increase of human quality of life.
PMID- 28685672
TI - MicroRNA-mediated MMP Regulation: Current Diagnostic and Therapeutic Strategies
for Metabolic Syndrome.
AB - INTRODUCTION: Metabolic Syndrome (MS) is a global socioeconomic problem rapidly
progressing in accordance with increasing Body Mass Index (BMI) and age. It is a
consortium of risk factors, such as dyslipidaemia, insulin resistance, leptin
resistance, reduced adiponectin, glucose intolerance, hyperglycemia, and
hypertension. Collectively, these factors accelerate the onset of type 2 diabetes
mellitus, cardiovascular disease, stroke, and certain cancers such as breast,
liver pancreatic, and colon cancer. Extracellular Matrix (ECM) and basement
membrane remodeling play a central role during pathogenesis of MS as they
regulate diverse cell functions including proliferation, differentiation, and
migration. Therefore, regulation of proteins that remodel the ECM offers
promising therapeutic opportunities for most of the MS. Matrix Metalloproteinases
(MMPs), a family of zinc dependent endopeptidases, are the main enzymes involved
in ECM remodeling. Emerging studies have reported altered levels of MMPs and the
Tissue Inhibitors of Metalloproteinases (TIMPs) during MS. A number of
pharmaceutical MMP inhibitors are being developed, but they have yet to be
recognized for clinical applications. CONCLUSION: Recently, microRNAs (~21-23
nucleotide, small non-coding, endogenous, single-stranded RNAs) have emerged as a
class of promising entities for therapeutic intervention due to their ability to
manipulate gene expression. The combined strategy of targeting ECM remodeling
through regulation of MMPs by small non-coding RNA has produced encouraging
results in pre-clinical studies for cancer and cardiovascular diseases. This
review serves to provide insight into the role of microRNAs as modulators of MS
and their potential as therapeutics tool through direct and indirect interactions
with the MMPs.
PMID- 28685673
TI - Physicochemical and Pharmacological Characterization of Permanently Charged
Opioids.
AB - BACKGROUND: The main aim of synthesizing permanently charged opioids is to ensure
that they do not enter the central nervous system. Such drugs can provide
analgesic activity with reduced sedation and other side effects on the central
nervous system. METHODS: We undertook a search of bibliographic databases for
peer-reviewed research literature and also summarized our published results in
this field. RESULTS: The present review focuses on the characterization of
permanently charged opioids by various physicochemical methods, and in vitro as
well as in vivo tests. The basicity and lipophilicity of opioid alkaloids are
discussed at the microscopic, speciesspecific level. Glucuronide conjugates of
opioids are also reviewed. Whereas the primary metabolite morphine-3-glucuronide
does not bind to opioid receptors with high affinity, morphine-6-glucuronide is a
potent analgesic, at least, partly due to its unexpectedly high lipophilicity. We
discuss the quaternary ammonium opioid derivatives of a permanent positive
charge, detailing their antinociceptive activity and effects on gastrointestinal
motility in various in vivo animal tests and in vitro studies. Compounds with
antagonistic activity are also reviewed. The last part of our study concentrates
on sulfate conjugates of morphine derivatives that display unique pharmacological
properties because they carry a negative charge at any pH value in the human
body. CONCLUSION: In conclusion, the findings of this review confirm the
importance of permanently charged opioids in the investigated fields of
pharmacology.
PMID- 28685674
TI - Review on anti-cancer activity in wild plants of the Middle East.
AB - Plants have been a source of medicine for thousands of years. In many different
cultures they became an integral part of local folklore. Plants have since become
a source of well-known drugs and pharmaceuticals that are widely used in modern
day medicine. Cancer is among the leading causes of mortality worldwide and the
number of new cases is expected to rise over the next 2 decades. Some herbal
medicines have a therapeutic effect which inhibits cancer via different
mechanisms. The Mediterranean basin is one of the richest biodiversity areas in
the world. In the Middle East region the use of medicinal plants for treating
cancer has been documented for generations in different cultures. In the present
review medicinal plants with confirmed data on active compounds and/or clear mode
of action are discussed, with the objective to provide the reader with a view on
the scientific studies concerning these plants activity, their active substances
and mode of action as known today. However, medicinal and herbal plants were
until recently mainly gathered from the wild, resulting in some of the commonly
used herbs becoming endangered species. Also, in many cases, the activity and
biochemical profile of plants harvested over different time spans and ecosystems
may vary, due to genetic diversity and different growth conditions. Rational
cultivation in most cases can ensure optimized yield with a uniform high quality
of products.
PMID- 28685675
TI - The Beneficial Effects of Sulfur-containing Amino Acids on Cisplatininduced
Cardiotoxicity and Neurotoxicity in Rodents.
AB - BACKGROUND: Cisplatin is one the most frequently used chemotherapeutic drugs for
several decades. Although its antineoplastic effect has been reported in
treatment of numerous malignances, various adverse effects seem to be the crucial
limiting factor for its administration. OBJECTIVE: Beside the most commonly
described nephro- and hepatotoxicity, cisplatin therapy is also accompanied with
gastrointestinal, reproductive, hematological, cardiovascular and neurological
side effects. Since it has been reported that cisplatin induce oxidative damage
in various tissues, it seems reasonable to investigate an antioxidant
supplementation as potential therapeutical approach for attenuation of cisplatin
toxicities. METHODS: We performed a structured search of bibliographic databases
for research literature using a focused review question and inclusion/exclusion
criteria. The quality of retrieved papers (101 in total) was appraised using
standard tools. RESULTS: Numerous antioxidants (such as thiol compounds,
polyphenols, vitamins, etc.) had been reported for their beneficial effects on
cisplatin-induced cardiotoxicity. The effects of various antioxidants, including
sulfur-containing amino acids, have also been explored for mitigation of
cisplatin neurotoxicity. However, the results for antioxidant supplementation in
reduction of cisplatin-induced toxicities are still to be applied in clinical
trials. CONCLUSION: Considering the facts that sulfur-containing amino acids: (a)
do not interfere with chemotherapeutics antitumor action; (b) do not exhibit any
toxic effect (unless applied in dose several times above the recommended); and
(c) produce significant protective effects on some cisplatin-induced toxicities
connected to augmentation of oxidative damage - it seems that their
administration can be harmless and protective supplementation against numerous
adverse effects of certain antineoplastic agents.
PMID- 28685676
TI - Recent Advances in Superparamagnetic Iron Oxide Based Nanoprobes as
Multifunctional Theranostic Agents for Breast Cancer Imaging and Therapy.
AB - BACKGROUND: Breast cancer accounts for nearly one in three cancers, and it is the
most common cancer diagnosed among women. The death rate of breast cancer is
estimated to be 14%. Hence, accurate diagnosis in early stage and effective
treatment in any stage are critical for the survival of breast cancer. Mammogram
has been the most common technique administered to detect breast cancer. However,
the radiation dose from mammogram is harmful to patients. Fortunately, magnetic
resonance imaging (MRI) can diagnose breast cancer without any radiation dose,
and enhanced MRI can make earlier and differential diagnosis. Therefore, as
contrast materials, superparamagnetic iron oxide based nanoprobes (SPIONs) have
generated a great deal of attention. OBJECTIVE: This review covers recent
advances in SPIONs as multifunctional theranostic agents. METHODS: Besides
synthesis and surface modification of SPIONs, passive and active targeted imaging
is also discussed. Moreover, a serial of potential therapy for breast cancer is
further described, such as photodynamic therapy, photothermal therapy,
chemotherapy and magnetic hyperthermia therapy. CONCLUSION: Preparation and
surface modification of SPIONs is critical for imaging diagnosis of breast cancer
and further potential treatment.
PMID- 28685677
TI - The Panomics Approach in Neurodegenerative Disorders.
AB - The molecular genetic technologies revolutionized the diagnostics of many
disorders. Thanks to the new molecular techniques and the rapid improvement of
the information technologies the number of mendelien inherited disorders have
increased rapidly in the last five years. The omics era brought radical changes
in the understanding of complex disorders and the underlying pathomechanisms.
However, in most complex disorders the genome wide association studies could not
clarify the genetic background even for disorders where a very strong
heritability had been observed. In this paper the changing concept of the
neurodegenerative disorders is discussed. The traditional classification of these
disorders was purely based on clinical symptoms and morphological signs in the
last century. Identifying the signature lesions of various neurodegenerative
disorders may reveal a common pathological pathways in these disorders. New
neuroimaging methods provided additional tools to assess pathological pathways in
vivo already in the early stages of the diseases. Visualizing in vivo amyloid
deposits and neuroinflammation improved our understanding of their role in
various neurodegenerative disorders. Genetics may be the most precise way to
identify the background of these disorders. However, there is only limited number
of cases where true association can be proved between the disorder and the
genetic mutations. Most of the neurodegenerative disorders seem to be
multifactorial and cannot be traced back to one single cause. In conclusion,
shifting from a classification based on symptomatology only to a modern
multidisciplinary approach, based on the constantly evolving panomics findings,
would improve our understanding of neurodegenerative diseases and could be the
basis of novel therapeutic research.
PMID- 28685678
TI - Glomerular Endothelium and its Impact on Glomerular Filtration Barrier in
Diabetes: Are the Gaps Still Illusive?
AB - BACKGROUND: Glomerular capillaries are lined with highly specialized fenestrated
endothelium which are primarily responsible to regulate high flux filtration of
fluid and small solutes. During filtration, plasma passes through the fenestrated
endothelium and basement membrane before it reaches the slit diaphragm, a
specialized type of intercellular junction that connects neighbouring podocytes.
METHODS: A PubMed search was done for recent articles on components of the
glomerular filtration barrier such as glomerular endothelial cells, podocytes and
glomerular basement membrane, and the effect of diabetes on these structures.
RESULTS AND CONCLUSION: Generally, the onset of kidney dysfunction in many
diabetic patients is characterized by albuminuria/proteinuria, a
pathophysiological event triggered by several factors including; (i) endothelial
activation and shading of glycocalyx, (ii) loss of endothelial cell function,
(ii) re-uptake of albumin by podocyte through a scavenger receptors and (iv)
rearrangement of podocyte cytoskeleton. Howeover, as podocyte effacement does not
always lead to proteinuria, the dynamic interplay between all constituents of the
glomerular filtration barrier including podocytes, endothelial cells and the
basement membrane may be fundamental for the effective filtration in healthy
individuals. Thus, a putative cross-talk amongst podocytes, endothelial cells and
the basement membrane in the homeostasis of glomerular function is envisaged.
Although, the exact nature of this cross-talk remains to be clearly elucidated,
it is possible that the interaction between: (i) glomerular endothelial cells and
podocytes, (ii) glomerular endothelial cells and glomerular basement membrane,
(iii) podocytes and glomerular basement membrane, and (iv) the simultaneous
interaction amongst the three components collectively underpin effective
filtration in healthy individuals. A comprehensive understanding of these
different interactions still remains elusive. The elucidation of these
multifaceted interactions will set the stage for greater understanding of the
pathophysiology of kidney dysfunction.
PMID- 28685679
TI - Clinical Approach to Diabetic Cardiomyopathy: A Review of Human Studies.
AB - BACKGROUND: Diabetic Cardiomyopathy (DC) has been defined as a distinct entity
characterized by the presence of diastolic or systolic cardiac dysfunction in a
diabetic patient in the absence of other causes for Cardiomyopathy, such as
coronary artery disease (CAD), hypertension (HTN), or valvular heart disease.
Diabetes affects every organ in the body and cardiovascular disease accounts for
two-thirds of the mortality in the diabetic population. Diabetes-related heart
disease occurs in the form of coronary artery disease (CAD), cardiac autonomic
neuropathy or DC. The prevalence of cardiac failure is high in the diabetic
population and DC is a common, but underestimated cause of heart failure in
diabetes. The strong association between diabetes and heart failure has fueled
intense human and animal research aimed at identifying the mechanisms underlying
diabetic myocardial disease. Despite significant progress made, the precise
pathogenesis of diabetic Cardiomyopathy is yet to be clearly defined.
Hyperglycemia, dyslipidemia and inflammation are thought to play key roles in the
generation of reactive oxygen or nitrogen species which are in turn involved.
METHODS: We have reviewed the up-to-date scientific literature addressing these
issues. RESULTS: The myocardial interstitium undergoes alterations resulting in
abnormal contractile function noted in DC. In the early stages of the disease,
diastolic dysfunction is the only abnormality, but systolic dysfunction
supervenes in the later stages with impaired left ventricular ejection fraction.
Transmitral Doppler echocardiography is usually used to assess diastolic
dysfunction, but tissue Doppler Imaging and Cardiac Magnetic Resonance Imaging
are being increasingly used for early detection of DC. Diabetic patients with
microvascular complications show the strongest association between diabetes and
Cardiomyopathy, an association that parallels the duration and severity of
hyperglycemia. CONCLUSION: The management of DC involves improvement in
lifestyle, control of glucose and lipid abnormalities, together with treatment of
hypertension and CAD, if present.
PMID- 28685680
TI - Attenuation of Diabetes-induced Cardiac and Subcellular Defects by Sulphur
containing Amino Acids.
AB - BACKGROUND: Patients with diabetes mellitus have an increased risk of mortality
due to cardiovascular complications. Supplementation with specific sulphur
containing amino acids is rapidly emerging as a possible therapeutic adjuvant for
diabetes and associated cardiovascular complications. OBSERVATIONS: It is well
known that oxidative stress plays an important role in the pathogenesis of
diabetes-induced cardiovascular disease, which is invariably associated with
abnormal blood lipid profile, insulin resistance and other symptoms of metabolic
syndrome. Cysteine and taurine are among the most common sulphur-containing amino
acids and their cellular levels decline during diabetes that may contribute to
the development of the cardiomyopathy. Although sulphur-containing agents exert
multiple actions on cellular and subcellular functions in the heart, they also
exhibit antioxidant properties and thus may exert beneficial effects in different
pathophysiological conditions. CONCLUSION: It is concluded that reduction of
oxidative stress by cysteine and taurine may serve as an important mechanism for
the attenuation of diabetes-induced subcellular and functional abnormalities in
the heart.
PMID- 28685681
TI - Exploiting Cancer Metal Metabolism using Anti-Cancer Metal-Binding Agents.
AB - Metals are vital cellular elements necessary for multiple indispensable
biological processes of living organisms, including energy transduction and cell
proliferation. Interestingly, alterations in metal levels and also changes in the
expression of proteins involved in metal metabolism have been demonstrated in a
variety of cancers. Considering this and the important role of metals for cell
growth, the development of drugs that sequester metals have become an attractive
target for the development of novel anti-cancer agents. Interest in this field
has surged with the design and development of new generations of chelators of the
thiosemicarbazone class. These ligands have shown potent anti-cancer and anti
metastatic activity in vitro and in vivo. Due to their efficacy and safe
toxicological assessment, some of these agents have recently entered multi-center
clinical trials as therapeutics for advanced and resistant tumors. This review
highlights the role, and changes in homeostasis, of metals in cancer and
emphasizes the pre-clinical development and clinical assessment of metal ion
binding agents, namely, thiosemicarbazones, as anti-tumor agents.
PMID- 28685682
TI - Advances in the prediction of protein aggregation propensity.
AB - Protein aggregation into beta-sheet-enriched insoluble assemblies is being found
to be associated with an increasing number of debilitating human pathologies,
such as Alzheimer's disease or type 2 diabetes, but also with premature aging.
Furthermore, protein aggregation represents a major bottleneck in the production
and marketing of protein-based therapeutics. A myriad of in vitro and in vivo
aggregation studies have shown that the aggregation propensity of a certain
polypeptide sequence is highly dependent on its intrinsic properties and, in most
cases, driven by specific short regions of high aggregation propensity. These
observations have fostered the development of a first generation of algorithms
aimed to predict protein aggregation propensities forom the protein sequence. A
second generation of programs able to map protein aggregation on protein
structures is emerging. In the present review, we describe representative
biocomputational approaches to evaluate the aggregation properties of protein
sequences and structures, while illustrating how they can become very useful
tools to target protein aggregation in biomedicine and biotechnology.
PMID- 28685683
TI - Applications of cellulose-based materials in sustained drug delivery systems.
AB - Bio-compatible, bio-degradable, and bio-available excipients are of critical
interest for drug delivery systems. Cellulose and its derivative-based excipients
have been well studied due to their green/ natural and unique encapsulation/
binding properties. They are often used in controlled/ sustained drug delivery
systems. In these applications, cellulose and its derivatives function generally
can modify the solubility/gelling behavior of drugs, resulting in different
mechanisms for controlling the release profiles of drugs. In this paper, the
current knowledge in the structure and chemistry of conventional cellulose
derivatives, and their applications in drug delivery systems are briefly
reviewed. The development of innovative cellulose-based materials, including
micro-cellulose (MC) and nano-cellulose (NC) in the applications of sustained
drug delivery, is also discussed.
PMID- 28685684
TI - Immune Modulation of Asian Folk Herbal Medicines and Related Chemical Components
for Cancer Management.
AB - Various exciting immunotherapies aiming to address the immune deficiency induced
by tumor and treatment hold promise in improving the life quality of life and
survival rate of cancer patients. It is thus becoming an important and rewarding
arena to develop some appropriate immune modulators for cancer prevention and/or
treatment. Exploitation of natural products-based immune modulators is of
particular imperative because the potential of numerous traditional herbal
medicines and edible mushrooms in boosting human immune system has long been
verified by folklore practices. This review summarizes the immune modulations of
various herbal medicines and edible mushrooms, their crude extracts, and/or key
chemical components that have been, at least partly, associated with their cancer
management. This article also tabulates the origin of species, key chemical
components, and clinical studies of these herbal medicines and edible mushrooms.
PMID- 28685685
TI - Hemicellulose from Plant Biomass in Medical and Pharmaceutical Application: A
Critical Review.
AB - Hemicellulose is the second most abundant plant polysaccharides after cellulose.
Due to the non-toxicity, abundance and biodegradability, recently more and more
attention has been focused on the exploration of hemicellulose as the potential
substrate for the production of liquid fuels and other value-added chemicals and
materials in different fields. Especially in the pharmaceutical and medical
field, hemicellulose currently has aroused growing concern in immune regulation,
bacteria inhibition, drug release, anti-caries, scaffold materials and anti-tumor
because of its unique special physiological characteristics including
biocompatibility, inhibiting cell mutation and anti-cancer effect, etc. In this
paper, we introduce the application of nature hemicellulose, its degradation
products, its derivatives and hemicellulose-based materials in the medical field.
Their properties and use effects are also discussed in detail. Moreover, the
extraction technologies of nature hemicelluloses, the preparation of
hemicellulose-derived products are reviewed here briefly. The recent trends and
perspectives of future development are highlighted.
PMID- 28685686
TI - HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitors: SAR and Lead Optimization
Using CoMFA and CoMSIA Studies (1995-2016).
AB - BACKGROUND: Design of inhibitors for HIV-1 reverse transcriptase inhibition (HIV
1 RT) is one of the successful chemotherapies for the treatment of HIV infection.
Among the inhibitors available for HIV-1 RT, non-nucleoside reverse transcriptase
inhibitors (NNRTIs) have shown to be very promising and clinically approved
drugs. However, the efficiency of many of these drugs has been reduced by the
drug-resistant variants of HIV-1 RT. The aim of the current review is to provide
a summary of lead optimization strategies from the 3D-QSARs studies on NNRTI
class from the past 21 years (1995 to 2016). METHODS: The conformation dependent
alignment based (CoMFA and CoMSIA) methods have been proven very successful
ligand based strategy in the drug design. Here, CoMFA and CoMSIA studies reported
for structurally distinct NNRTIs including thiazolobenzimidazole,
dipyridodiazepinone, 1,1,3-trioxo [1,2,4]-thiadiazine, formimidoester disulfides,
thiocarbamate, thiazolidinone derivatives, etc. have been discussed in detail. In
addition, we explore the position of the functional groups that drive the protein
ligand interaction. RESULTS: The structure-activity relationship (SAR) revealed
from CoMFA and CoMSIA studies of these drug classes is not only in agreement with
the structure-based method but also provides an efficient way of lead
optimization. In addition to molecular docking experiments, protein-ligand
interaction fingerprints were calculated in order to understand the common
binding mode of NNRTI compounds. CONCLUSION: Overall, this review enlightens the
protein-ligand interactions with a detailed SAR discussion for chemotypes. Such
discussion will help medicinal chemist to gain a better understanding for the
design of novel and promising NNRTI candidates.
PMID- 28685688
TI - Anti-oxidative and Anti-microbial Activities of Purified MPN-1-1 from Persicaria
nepalensis (Meisn.) Miyabe.
AB - BACKGROUND: Persicaria is a genus of flowering plants generally used for
traditional medicine and nutritional supplements in tropical and subtropical East
Asian countries. Previous studies have shown that Persicaria extracts alleviate
lipid peroxidation, hypertension, and inflammation. OBJECTIVE: We investigated
the anti-oxidative and anti-microbial effects of ethanol extracts of Persicaria
nepalensis (Meisn.) Miyabe, and isolated and identified an active compound, MPN-1
1 from the ethanol extracts. RESULTS: Anti-oxidative values, as indicated by the
Oxygen Radical Absorbance Capacity (ORAC) assay, were enhanced by treatment with
Persicaria nepalensis (Meisn.) Miyabe ethanol extracts, and bacterial growth was
inhibited. The active compound (MPN-1-1), which was further isolated and purified
from a Persicaria nepalensis (Meisn.) Miyabe ethanol extract by medium pressure
liquid chromatography (MPLC), also had strong anti-oxidative and anti-microbial
activity. 1H-NMR spectroscopy identified MPN-1-1 as a 1-ethenyl-4,8-dimethoxy-9H
pyrido(3,4-beta) indole compound, which is an alkaloid. CONCLUSION: Our results
provide evidence that Persicaria nepalensis (Meisn.) Miyabe extract has strong
physiological activity without any toxic effects, and furthermore, MPN-1-1 can be
potentially utilized as a natural dietary supplement as well as an anti-oxidant.
PMID- 28685687
TI - Modulators of Acetylcholinesterase Activity: From Alzheimer's Disease to Anti
Cancer Drugs.
AB - BACKGROUND: Acetylcholinesterase (AChE) is involved in the termination of impulse
transmission by rapid hydrolysis of the neurotransmitter acetylcholine in
numerous cholinergic pathways in the central and peripheral nervous systems. The
enzyme inactivation leads to acetylcholine accumulation, hyperstimulation of
nicotinic and muscarinic receptors, and disrupted neurotransmission. Hence,
acetylcholinesterase inhibitors, interacting with the enzyme as their primary
target, are applied as relevant drugs for different neurodegenerative diseases
(such as Alzheimer's and Parkinson's) as well as toxins. At the same time, there
are increasing evidence that in non-neuronal context, AChE is involved in the
regulation of cell proliferation, differentiation, apoptosis and cell-cell
interaction. An irregular expression of AChE has been found in different types of
tumors, suggesting the involvement of AChE in the regulation of tumor
development. Having all this in mind, there is a possibility that some AChE
inhibitors could be used as anti-cancer agents. OBJECTIVE: This contribution will
discuss a broad range of possible application of different AChE inhibitors as
drugs, from well-known anti-Alzheimer's disease drugs to their use in cancer
treatment in future. Emphasis will be put on various known AChE inhibitors
classes, whose application as drugs could be controversy, as well as on newly
investigated natural products, which can also modulate AChE activity. CONCLUSION:
It is not clear a patient treated for neurodegenerative condition prone to
increased risk for some types of cancer and vice versa. This is necessary to keep
in mind during rational drug design process for all therapies, which are based on
AChE as a target molecule.
PMID- 28685689
TI - Arylurea Derivatives: A Class of Potential Cancer Targeting Agents.
AB - Arylurea derivatives, an important class of small molecules, have received
considerable attention in recent years due to their wide range of biological
applications. Various molecular targeted agents with arylurea scaffold as
potential enzyme/receptor inhibitors were constructed with the successful
development of sorafenib and regorafenib. This review focuses on those arylureas
possessing anti-cancer activities from 2010 to date. According to their different
mechanisms of action, these arylureas are divided into the following six
categories: (1) Ras/Raf/MEK/ERK signaling pathway inhibitors; (2) tumor
angiogenesis inhibitors, their targets include Vascular Endothelial Growth Factor
Receptors (VEGFRs), Fibroblast Growth Factor Receptors (FGFRs), Platelet-Derived
Growth Factor Receptors (PDGFRs), Epidermal Growth Factor Receptors (EGFRs),
Insulin-Like Growth Factor 1 Receptor (IGF-1R), Fmslike Tyrosine Kinase 3 (FLT3),
c-Kit, MET, and Smoothened (Smo); (3) PI3K/AKT/mTOR signaling pathway inhibitors;
(4) cell cycle inhibitors, their targets include Checkpoint Kinases (Chks),
Cyclin- Dependent Kinases (CDKs), Aurora, SUMO activating enzyme 1 (SUMO E1),
tubulin, and DNA; (5) tumor differentiation, migration, and invasion inhibitors,
their targets include Matrix Metalloproteinases (MMPs), LIM kinase (Limk),
Nicotinamide Phosphoribosyltransferase (Nampt), and Histone Deacetylase (HDAC);
(6) arylureas from the rational modification of natural products. This review
focuses on the Structure-Activity Relationships (SARs) of these arylureas. The
structural evolution and current status of some typical anti-cancer agents used
in clinic and/or in clinical trials are emphasized.
PMID- 28685690
TI - Can Untargeted Metabolomics Be Utilized in Drug Discovery/Development?
AB - Untargeted metabolomics is a promising approach for reducing the significant
attrition rate for discovering and developing drugs in the pharmaceutical
industry. This review aims to highlight the practical decision-making value of
untargeted metabolomics for the advancement of drug candidates in drug
discovery/development including potentially identifying and validating novel
therapeutic targets, creating alternative screening paradigms, facilitating the
selection of specific and translational metabolite biomarkers, identifying
metabolite signatures for the drug efficacy mechanism of action, and
understanding potential drug-induced toxicity. The review provides an overview of
the pharmaceutical process workflow to discover and develop new small molecule
drugs followed by the metabolomics process workflow that is involved in
conducting metabolomics studies. The pros and cons of the major components of the
pharmaceutical and metabolomics workflows are reviewed and discussed. Finally,
selected untargeted metabolomics literature examples, from primarily 2010 to
2016, are used to illustrate why, how, and where untargeted metabolomics can be
integrated into the drug discovery/preclinical drug development process.
PMID- 28685692
TI - Molecular Determinants of Chronic Liver Disease as Studied by NMR-Metabolomics.
AB - Chronic liver diseases are one of the major causess of mortality worldwide. It
can manifest through many different forms including chronic virus infection,
alcohol abuse, metabolic syndromes such as non-alcoholic fatty liver disease and
non-alcoholic steatohepatitis. At early stages, the liver can repair the damage
produced by the insult. However, upon continuous damage, the accumulation of
molecules triggers fibrosis, which subsequently progresses towards cirrhosis and,
ultimately, hepatocarcinoma. Early diagnosis of liver disease and a proper
staging of fibrosis are crucial in therapy since drugs are only effective at
incipient and intermediate stages of the disease. In this context, liver biopsy
is the gold standard, but it is invasive and can produce complications.
Metabolomics has emerged as a potent discipline to identify new biomarkers in a
non-invasive way. Here, we compile and critically review the existing NMR-based
metabolomics studies on chronic liver diseases, specifically covering non
alcoholic fatty liver disease, non-alcoholic steatohepatitis, alcoholic liver
disease and those produced by virus infection.
PMID- 28685693
TI - Multi-Targeted Anticancer Agents.
AB - There is a great demand for the development of novel anticancer drugs, due to the
increasing morbidity and high mortality of cancer. To date, chemotherapy still
plays a central role in the clinical treatment of cancer, but this role is being
reduced by targeted therapies. Since cancer is a complicated and multiple genes
involved disease, drugs that act at multiple targets can enhance efficacy and
lower drug resistance, and are thought to be the future of novel anticancer drug
development. In this paper, we discuss the recent development of "single
molecule, multi-target" anticancer agents that combine two or more pharmacophores
in a single molecule, including organic multitargeted anticancer agents and metal
based complexes such as platinum, ruthenium, iridium and rhodium complexes. These
efforts will contribute to clinical cancer therapy and benefit patients in the
future.
PMID- 28685694
TI - Multi-targeting Strategies for Alzheimer's Disease Therapeutics: Pros and Cons.
AB - Alzheimer's Disease (AD) is a single major cause of dementia in middle to old age
individuals involving several different etiopathological mechanisms that are yet
to be properly characterized. Major invariant and characteristic features consist
of the progressive cerebral deposition of the Amyloid beta-protein (Abeta) and
the neurofibrillary degeneration through Neurofibrillary Tangles (NFT) formed by
hyperphosphorylation of the tau proteins in the regions of the brain that deal
with memory and cognition. There are at least five subgroups of AD that can be
identified by determining Cerebrospinal Fluid (CSF) levels of Abeta1-42, tau and
ubiquitin. This multifactorial nature of the disease thus demands promising
approaches for the development of rational disease-modifying drugs. A large
number of agents have been discovered against individual targets but the success
rate is very low and the number of compounds progressing to regulatory review is
among the lowest found in any therapeutic area. A very promising modern approach
solicits the design of Multi-Target-Directed Ligands (MTDLs) based on the "one
molecule multiple targets" paradigm that has been specifically adopted for the
treatment of disorders with complex pathological mechanisms. AD is one such
disorder in which MTDL has found applicability. This review aims at providing an
overview of the research carried out in discovering more efficient treatment
against AD using MTDL, with a goal to ascertain safer drugs.
PMID- 28685691
TI - Metabolomics Applications in Precision Medicine: An Oncological Perspective.
AB - Nowadays, cancer therapy remains limited by the conventional one-size-fits-all
approach. In this context, treatment decisions are based on the clinical stage of
disease but fail to ascertain the individual 's underlying biology and its role
in driving malignancy. The identification of better therapies for cancer
treatment is thus limited by the lack of sufficient data regarding the
characterization of specific biochemical signatures associated with each
particular cancer patient or group of patients. Metabolomics approaches promise a
better understanding of cancer, a disease characterized by significant
alterations in bioenergetic metabolism, by identifying changes in the pattern of
metabolite expression in addition to changes in the concentration of individual
metabolites as well as alterations in biochemical pathways. These approaches hold
the potential of identifying novel biomarkers with different clinical
applications, including the development of more specific diagnostic methods based
on the characterization of metabolic subtypes, the monitoring of currently used
cancer therapeutics to evaluate the response and the prognostic outcome with a
given therapy, and the evaluation of the mechanisms involved in disease relapse
and drug resistance. This review discusses metabolomics applications in different
oncological processes underlining the potential of this omics approach to further
advance the implementation of precision medicine in the oncology area.
PMID- 28685695
TI - Quantum-Mechanics Methodologies in Drug Discovery: Applications of Docking and
Scoring in Lead Optimization.
AB - The development and application of quantum mechanics (QM) methodologies in
computer- aided drug design have flourished in the last 10 years. Despite the
natural advantage of QM methods to predict binding affinities with a higher level
of theory than those methods based on molecular mechanics (MM), there are only a
few examples where diverse sets of protein-ligand targets have been evaluated
simultaneously. In this work, we review recent advances in QM docking and scoring
for those cases in which a systematic analysis has been performed. In addition,
we introduce and validate a simplified QM/MM expression to compute protein-ligand
binding energies. Overall, QMbased scoring functions are generally better to
predict ligand affinities than those based on classical mechanics. However, the
agreement between experimental activities and calculated binding energies is
highly dependent on the specific chemical series considered. The advantage of
more accurate QM methods is evident in cases where charge transfer and
polarization effects are important, for example when metals are involved in the
binding process or when dispersion forces play a significant role as in the case
of hydrophobic or stacking interactions.
PMID- 28685696
TI - An In Vivo Rat alpha-D-glucose Stable Isotope Homeostasis Drug Discovery Screen:
A Targeted Metabolomics Approach.
AB - We have developed a targeted metabolomics screen which consists of using two
isotopically labeled glucose compounds to conduct a dual oral glucose tolerance
test in rats. This dual isotopic oral glucose tolerance test (DIS-OGTT) can be
used to select drug candidates that have "on"- target or have "off"-target
effects on oral glucose absorption, hepatic glucose production or glucose
disposal. The DIS-OGTT assay utilized intravenously administered [6-13C1-6, 6'
2H2]-glucose and orally administered [U-13C6] glucose to monitor glucose
homeostasis. In the experiment, a constant intravenous dose of [6-13C1-6, 6'-2H2]
glucose was converted in vivo to a series of [M+1] glucose isotopomers and
unlabeled [M] glucose via gluconeogenesis while the orally administered [U-13C6]
glucose was converted to a series of [M+3] and [M+2] glucose isotopomers via
gluconeogenesis. The detection platform of the assay was based on a negative mode
electrospray ionization liquid chromatography tandem mass spectrometry method
where the deprotonated glucose anion and its various isotopomers were quantitated
in rat plasma using multiple reaction monitoring techniques. The in vivo rat DIS
OGTT assay was a sensitive method for understanding drug candidates underlying
postprandial effects on glucose absorption, hepatic glucose production, and
insulin controlled glucose disposal. Since glucose derivatization was not
required for this assay, a higher sample throughput DIS-OGTT was achieved.
PMID- 28685697
TI - Does Pharmacological Therapy Still Play a Role in Preventing Sudden Death in
Surgically Treated Tetralogy of Fallot?
AB - Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart disease,
with a familial recurrence risk of 3%. Despite performing an optimal surgical
repair, TOF patients may feature a poor medium and long-term survival rate:
atrial re-entrant tachycardia will develop in more than 30% of patients and high
grade ventricular arrhythmias will be seen in about 10% of patients. These life
threatening arrhythmias and consequent sudden death continue to represent serious
complications following TOF repair. Radiofrequency ablation and implantable
cardioverter defibrillator are today the most effective therapeutic tools in
these subjects, while the administration of antiarrhythmic drugs (Ib agents, beta
blockers, and amiodarone), widely prescribed in the past, is now limited to few
conditions. However pharmacological therapy still plays a role in the management
of those patients who are resistant to the above stated invasive
electrophysiological treatments.
PMID- 28685698
TI - Medical Therapy for Long QT Syndrome.
AB - Long QT syndrome (LQTS) is an arrhythmogenic disorder characterized by
repolarization abnormalities with a tendency to cause life threatening cardiac
events. The first manifestation of the syndrome may be sudden death, therefore,
early diagnosis and therapy is of great importance. LQTS can be congenital or
acquired. The latter is most commonly seen in hospitalized patients and such
individuals have an easily recognizable and reversible precipitating factor
(electrolyte disturbances, certain drugs etc.). Congenital LQTS, a less prevalent
condition, is considered to be part of the greater family of disorders called
channelopathies. Extensive research over the past decade allowed better
understanding of the underlying molecular mechanisms and unmasking of the genetic
substrate of these patients. Both pharmacological and interventional therapies
(left cardiac sympathetic denervation, ICDs) have been used in the treatment of
congenital long-QT syndrome. This review will focus solely on the pharmacologic
therapy of this potentially lethal inherited disorder summarizing current
knowledge regarding b-blocker use, taking into account novel and more targeted
approaches such as gene-specific therapy.
PMID- 28685699
TI - Pharmacological Treatment of Vagal Hyperactivity, a Rare but Potentially Fatal
Cause of Sudden Cardiac Death.
AB - Vasovagal reaction, resulting in bradycardia and/or hypotension in response to a
number of stimuli, is usually self-limiting, but potentially life-threatening
exceptions have been described. Pharmacological treatment of proven efficacy is
still lacking and the administered compounds are often chosen on the basis of
either case reports or outdated small studies with a short-term follow up. In
refractory cases, pacemaker implantation may be considered, although no responder
patients represent a severe challenge for clinicians. The aim of this review is
to examine the state of the art about this controversial issue.
PMID- 28685700
TI - Substituted Benzamides from Anti-inflammatory and p38 Kinase Inhibitors to
Antitubercular Activity: Design, Synthesis and Screening.
AB - BACKGROUND: Twenty one amide compounds possessing phenoxy/benzyloxy/pyridinyl
groups have been synthesized by benzoylation of respective amines in presence of
base with moderate to encouraging yields. Upon confirmation of structure,
compounds were subjected for p38 kinase inhibitory, anti-inflammatory,
antimicrobial and antitubercular activities. METHOD: Anti-inflammatory activity
was determined using carrageenan induced rat paw edema model while p38 kinase
inhibitory activity was studied using ELISA method and serial dilution method was
employed to determine MICs. Two compounds 4g and 4n showed over 30% p38 kinase
inhibitory activity at 10 uM and best anti-inflammatory activity was found for
compounds 4g, 4i, 4n and 4o which exhibited to reduce paw edema over 70%.
Compound 4b was observed to be the most potent against gram +ve organisms with
MIC value of 1.6 uG/mL and compound 4u displayed potent antibacterial activity
against gram negative organisms. CONCLUSION: Most encouraging antitubercular
activity was noticed for compounds 4u, 4r and 4k with 6.25, 12.5 and 12.5 uG/mL
Further, in order to know the binding site interactions, a docking simulations of
compounds was performed. These preliminary results will certainly show fruitful
directions to improve the activities of compounds.
PMID- 28685701
TI - The Role of Quinidine in the Pharmacological Therapy of Ventricular Arrhythmias
'Quinidine'.
AB - Historically, quinidine was the first medicine used in the therapy of heart
arrhythmias. Studies in the early 20th century identified quinidine, a
diastereomer of the antimalarial quinine, as the most potent of the
antiarrhythmic substances extracted from the cinchona plant. Quinidine is used by
the 1920s, as an antiarrhythmic agent to maintain sinus rhythm after the
conversion from atrial flutter or atrial fibrillation and to prevent recurrence
of ventricular tachycardia or ventricular fibrillation. Its value in chronic
prophylaxis of relapse of ventricular arrhythmia was brought under suspicion
after publishing of meta analysis that showed that the application of quinidine
increases mortality. Due to numerous proofs of increased risk for the appearance
of ventricular arrhythmia and sudden death, as well as a number of other adverse
effects and drug interactions, quinidine was withdrawn from use and in the recent
years has become unavailable in many countries. On the other hand, recent studies
have demonstrated that quinidine is the only oral medication that has
consistently shown efficacy in preventing arrhythmias and terminating storms due
to recurrent ventricular fibrillation, in patients with Brugada syndrome,
idiopathic ventricular fibrillation and early repolarization syndrome. Quinidine
is also the only antiarrhythmic drug that normalized the QT interval in patients
with the congenital short QT syndrome. The aim of this review is to provide good
insight into pro and contra arguments for quinidine use in ventricular
arrhythmias evidence based on recently published literature.
PMID- 28685702
TI - A Focus on Pharmacological Management of Catecholaminergic Polymorphic
Ventricular Tachycardia.
AB - Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a channelopathy
characterized by adrenergic mediated ventricular arrhythmia. Untreated CPVT is a
malignant syndrome with more than 50% of arrhythmic events and up to 25% of fatal
or near-fatal cardiac events at 8 years follow-up. Prevention of sudden cardiac
death starts with exclusion of competitive sports. Beta blockers (BB) are the
cornerstone pharmacological therapy for the prevention of cardiac event in CPVT
patients. Dose of BB should be highly tolerable, preferably nadolol. Efficiency
of BB is undeniable but uncompleted. Therefore, on top of BB, one can propose the
use of Calcium channel blockers or Class 1c antiarrythmic drugs. Indeed
Flecainide allows reducing exercise- induced premature ventricular contraction
and ventricular arrhythmia. Pharmacological management should be a stepwise
approach with BB as the first line of choice. At each step of therapeutic
changes, heart rhythm during exercise should be monitored by Holter monitoring
and exercise testing. If the pharmacological management fails, left cardiac
sympathetic denervation or implantation of cardioverter defibrillator should be
considered.
PMID- 28685703
TI - Intoxication with alcohol at the time of self-harm and pre-existing involvement
with mental health services are associated with a pre-disposition to repetition
of self-harming behavior in a large cohort of older New Zealanders presenting
with an index episode of self-harm.
AB - The paper on predictors of repeat self-harm and suicide by Cheung et al. (2017),
which has been chosen by the editorial team as paper of the month for this issue
of International Psychogeriatrics, makes a very useful contribution to the study
of self-harm and suicide in late life. Of 339 individuals presenting with an
index episode of self-harm to one of seven Emergency Departments (EDs) in New
Zealand, close to 15% harmed themselves again within one year and for nearly one
in six of these 50 people, the repeat episode was fatal. Having alcohol in the
blood and already being engaged with mental health services at the time of the
index episode both had some utility in predicting the occurrence of a further
self-harm episode. While it is encouraging that mental health services look to
have been focusing on those who turned out to be at highest risk, clinicians may
need to be particularly vigilant when following up individuals who had been
drinking alcohol at the time of an initial self-harm presentation. This study
also emphasizes the high risk of recurrent self-harm and completed suicide in
those older adults who harm themselves and survive the initial episode. It
deserves to be widely cited and gives some direction for future research on
interventions designed to diminish the recurrence of self-harm in those of our
patients who have presented to an ED with an initial self-harm episode.
PMID- 28685704
TI - Prostate Involvement in a Patient with Follicular Lymphoma.
PMID- 28685705
TI - Chronic Active Parietal Osteomyelitis Due to Salmonella typhi in a Patient with
Sickle Cell Anemia.
PMID- 28685706
TI - Localization of massless Dirac particles via spatial modulations of the Fermi
velocity.
AB - The electrons found in Dirac materials are notorious for being difficult to
manipulate due to the Klein phenomenon and absence of backscattering. Here we
investigate how spatial modulations of the Fermi velocity in two-dimensional
Dirac materials can give rise to localization effects, with either full (zero
dimensional) confinement or partial (one-dimensional) confinement possible
depending on the geometry of the velocity modulation. We present several exactly
solvable models illustrating the nature of the bound states which arise,
revealing how the gradient of the Fermi velocity is crucial for determining
fundamental properties of the bound states such as the zero-point energy. We
discuss the implications for guiding electronic waves in few-mode waveguides
formed by Fermi velocity modulation.
PMID- 28685707
TI - Lead and selenite adsorption at water-goethite interfaces from first principles.
AB - The complexation of toxic and/or radioactive ions on to mineral surfaces is an
important topic in geochemistry. We apply periodic-boundary-conditions density
functional theory (DFT) molecular dynamics simulations to examine the
coordination of Pb(II), [Formula: see text], and their contact ion pairs to
goethite (1 0 1) and (2 1 0) surfaces. The multitude of Pb(II) adsorption sites
and possibility of Pb(II)-induced FeOH deprotonation make this a complex problem.
At surface sites where Pb(II) is coordinated to three FeO and/or FeOH groups, and
with judicious choices of FeOH surface group protonation states, the predicted Fe
Pb distances are in good agreement with EXAFS measurements. Trajectories where
Pb(II) is in part coordinated to only two surface Fe-O groups exhibit larger
fluctuations in Pb-O distances. Pb(II)/[Formula: see text] contact ion pairs are
at least metastable on goethite (2 1 0) surfaces if the [Formula: see text] has a
monodentate Se-O-Fe bond. Our DFT-based molecular dynamics calculations are a
prerequisite for calculations of finite temperature equilibrium binding constants
of Pb(II) and Pb(II)/[Formula: see text] ion pairs to goethite adsorption sites.
PMID- 28685708
TI - Soft-x-ray-induced spin-state switching of an adsorbed Fe(II) spin-crossover
complex.
AB - For probing the nature of spin-state switching in spin-crossover molecules
adsorbed on surfaces, x-ray absorption spectroscopy has emerged as a powerful
tool due to its high sensitivity and element selectivity in tracing even subtle
electronic, magnetic, or chemical changes. However, the x-rays itself can induce
a spin transition and might have unwanted influence while investigating the
effect of other stimuli such as temperature or light, or of the surface, on the
spin switching behaviour. Herein, we present the spin switching of an Fe(II)
complex adsorbed on a highly oriented pyrolytic graphite surface with particular
emphasis on the x-ray-induced switching. For a submonolayer coverage, the complex
undergoes a complete and reversible temperature- and light-induced spin
transition. The spin states are switched both ways by x-rays at 5 K, i.e. from
the high-spin state to the low-spin state or vice versa, depending on the
relative amount of each species. Furthermore, we quantify the fraction of
molecules undergoing soft x-ray-induced photochemistry, a process which results
in an irreversible low-spin state component, for a particular exposure time. This
can be greatly suppressed by reducing the beam intensity.
PMID- 28685709
TI - Alane adsorption and dissociation on the Si(0 0 1) surface.
AB - We used DFT to study the energetics of the decomposition of alane, AlH3, on the
Si(0 0 1) surface, as the acceptor complement to PH3. Alane forms a dative bond
with the raised atoms of silicon surface dimers, via the Si atom lone pair. We
calculated the energies of various structures along the pathway of successive
dehydrogenation events following adsorption: AlH2, AlH and Al, finding a gradual,
significant decrease in energy. For each stage, we analyse the structure and
bonding, and present simulated STM images of the lowest energy structures.
Finally, we find that the energy of Al atoms incorporated into the surface,
ejecting a Si atom, is comparable to Al adatoms. These findings show that Al
incorporation is likely to be as precisely controlled as P incorporation, if
slightly less easy to achieve.
PMID- 28685710
TI - Effect of defects on the small polaron formation and transport properties of
hematite from first-principles calculations.
AB - Hematite (alpha-Fe2O3) is a promising candidate as a photoanode material for
solar-to-fuel conversion due to its favorable band gap for visible light
absorption, its stability in an aqueous environment and its relatively low cost
in comparison to other prospective materials. However, the small polaron
transport nature in alpha-Fe2O3 results in low carrier mobility and conductivity,
significantly lowering its efficiency from the theoretical limit. Experimentally,
it has been found that the incorporation of oxygen vacancies and other dopants,
such as Sn, into the material appreciably enhances its photo-to-current
efficiency. Yet no quantitative explanation has been provided to understand the
role of oxygen vacancy or Sn-doping in hematite. We employed density functional
theory to probe the small polaron formation in oxygen deficient hematite, N-doped
as well as Sn-doped hematite. We computed the charged defect formation energies,
the small polaron formation energy and hopping activation energies to understand
the effect of defects on carrier concentration and mobility. This work provides
us with a fundamental understanding regarding the role of defects on small
polaron formation and transport properties in hematite, offering key insights
into the design of new dopants to further improve the efficiency of transition
metal oxides for solar-to-fuel conversion.
PMID- 28685711
TI - Static and time-resolved mid-infrared spectroscopy of Hg0.95Cd0.05Cr2Se4 spinel.
AB - Static and time-resolved mid-infrared spectroscopy of ferromagnetic single
crystal Hg0.95Cd0.05Cr2Se4 was performed below the absorption edge, in order to
reveal the origin of the electronic transitions contributing to the magneto
optical properties of this material. The mid-infrared spectroscopy reveals a
strong absorption peak around 0.236 eV which formerly was assigned to a
transition within the selenide-chromium complexes ([Formula: see text] Se-Cr2+).
To reveal the sensitivity of the transition to the magnetic order, we performed
the studies in a temperature range across the Curie temperature and magnetic
fields across the value at which the saturation of ferromagnetic magnetization
occurs. Despite the fact that the Curie temperature of this ferromagnetic
semiconductor is around 107 K, the intensity of the mid-infrared transition
reduces substantially increasing the temperature, so that already at 70 K the
absorption peak is hardly visible. Such a dramatic decrease of the oscillator
strength is observed simultaneously with the strong red-shift of the absorption
edge in the magnetic semiconductor. Employing a time-resolved pump-and-probe
technique enabled us to determine the lifetime of the electrons in the excited
state of this optical transition. In the temperature range from 7 K to 80 K, the
lifetime changes from 3 ps to 6 ps. This behavior agrees with the phenomenon of
giant oscillator strength described earlier for weakly bound excitons in
nonmagnetic semiconductors.
PMID- 28685712
TI - Effects of Traditional Chinese Medicine Shensong Yangxin Capsules on Heart Rhythm
and Function in Congestive Heart Failure Patients with Frequent Ventricular
Premature Complexes: A Randomized, Double-blind, Multicenter Clinical Trial.
AB - BACKGROUND: Pharmacological therapy for congestive heart failure (CHF) with
ventricular arrhythmia is limited. In the study, our aim was to evaluate the
effects of Chinese traditional medicine Shensong Yangxin capsules (SSYX) on heart
rhythm and function in CHF patients with frequent ventricular premature complexes
(VPCs). METHODS: This double-blind, placebo-controlled, multicenter study
randomized 465 CHF patients with frequent VPCs to the SSYX (n = 232) and placebo
groups (n = 233) for 12 weeks of treatment. The primary endpoint was the VPCs
monitored by a 24-h ambulatory electrocardiogram. The secondary endpoints
included the left ventricular ejection fraction (LVEF), left ventricular end
diastolic diameter, N-terminal pro-brain natriuretic peptide (NT-proBNP), New
York Heart Association (NYHA) classification, 6-min walking distance (6MWD),
Minnesota Living with Heart Failure Questionnaire (MLHFQ) scores, and composite
cardiac events (CCEs). RESULTS: The clinical characteristics were similar at
baseline. SSYX caused a significantly greater decline in the total number of VPCs
than the placebo did (-2145 +/- 2848 vs. -841 +/- 3411, P < 0.05). The secondary
endpoints of the LVEF, NYHA classification, NT-proBNP, 6MWD, and MLHFQ scores
showed a greater improvements in the SSYX group than in the placebo group
(DeltaLVEF at 12th week: 4.75 +/- 7.13 vs. 3.30 +/- 6.53; NYHA improvement rate
at the 8th and 12th week: 32.6% vs. 21.8%, 40.5% vs. 25.7%; mean level of NT
proBNP in patients with NT-proBNP >=125 pg/ml at 12th week: -122 [Q1, Q3: -524,
0] vs. -75 [Q1, Q3: -245, 0]; Delta6MWD at 12th week: 35.1 +/- 38.6 vs. 17.2 +/-
45.6; DeltaMLHFQ at the 4th, 8th, and 12th week: -4.24 +/- 6.15 vs. -2.31 +/-
6.96, -8.19 +/- 8.41 vs. -3.25 +/- 9.40, -10.60 +/- 9.41 vs. -4.83 +/- 11.23, all
P < 0.05). CCEs were not different between the groups during the study period.
CONCLUSIONS: In this 12-week pilot study, SSYX was demonstrated to have the
benefits of VPCs suppression and cardiac function improvement with good
compliance on a background of standard treatment for CHF. TRIAL REGISTRATION:
www.chictr.org.cn, ChiCTR-TRC-12002061
(http://www.chictr.org.cn/showproj.aspx?proj=7487) and Clinicaltrials.gov,
NCT01612260 (https://clinicaltrials.gov/ct2/show/NCT01612260).
PMID- 28685713
TI - Improved Fertility Following Enucleation of Intramural Myomas in Infertile Women.
AB - BACKGROUND: The relationship between intramural myomas and fertility remains
unclear. The main debate rests on whether cavity-distorting intramural myomas
(CDMs) adversely affect fertility more than non-CDMs. We aimed to compare the
effects of enucleating non-CDMs and CDMs on fertility improvement in females with
unexplained infertility. METHODS: We prospectively recruited 83 women undergoing
myomectomy for unexplained infertility with intramural myomas between June 2008
and November 2012 and classified them into non-CDMs group (n = 45) and CDMs group
(n = 38). We then compared postoperative infertility rates, spontaneous pregnancy
rates, pregnancy outcomes, live birth rates, and obstetric complications. For
continuous variables, we calculated the mean +/- standard deviation, median and
interquartile range, and analyzed the data using Student's t-test and the Mann
Whitney U-test. For categorical variables, the Pearson's Chi-square test, the
continuity correction test, and Fisher's exact test were used. RESULTS: Patients'
demographics and myoma characteristics were comparable between the two groups.
The overall spontaneous pregnancy rate increased from 0% to 68.42% following
myomectomy. The postoperative infertility rate was significantly higher in the
non-CDMs group than that in the CDMs group (50.00% vs. 23.53%, t = 5.579, P =
0.018), whereas the postoperative spontaneous pregnancy rate was significantly
lower in the non-CDMs group than that in the CDMs group (47.62% vs. 70.59%, t =
4.067, P = 0.044). Compared with the enucleation of non-CDM, the enucleation of
CDM patients was a protective factor for the fertility restoration (risk ratio
[RR] = 3.717, 95% confidence interval [CI]: 1.284-10.753, P = 0.015), although
postoperative fertility restoration declined with age (RR = 1.141, 95% CI: 1.005
1.295, P = 0.041). CONCLUSIONS: Intramural myomas are associated with impaired
fertility. Women experiencing unexplained infertility, and possessing intramural
myomas, have a better chance of conception following myomectomy, and these
benefits are more obvious for younger patients and patients with CDM.
PMID- 28685714
TI - Comparison of Efficacy and Safety between First and Second Generation Drug
eluting Stents in Patients with Stable Coronary Artery Disease: A Single-center
Retrospective Study.
AB - BACKGROUND: Lots of trials demonstrate that second-generation drug-eluting stents
(G2-DES), with their improved properties, offer significantly superior efficacy
and safety profiles compared to first generation DES (G1-DES) for patients with
coronary artery disease (CAD) receiving percutaneous coronary intervention (PCI).
This study aimed to verify the advantage of G2-DES over G1-DES in Chinese
patients with stable CAD (SCAD). METHODS: For this retrospective observational
analysis, 2709 SCAD patients with either G1-DES (n = 863) or G2-DES (n = 1846)
were enrolled consecutively throughout 2013. Propensity score matching (PSM) was
applied to control differing baseline factors. Two-year outcomes, including major
adverse coronary events as well as individual events, including target vessel
related myocardial infarction, target lesion revascularization (TLR), target
vessel revascularization, and cardiogenic death were evaluated. RESULTS: The
incidence of revascularization between G1- and G2-DES showed a trend of
significant difference with a threshold P - value (8.6% vs. 6.7%, chi2 = 2.995, P
= 0.084). G2-DES significantly improved TLR-free survival compared to G1-DES
(96.6% vs. 97.9%, P = 0.049) and revascularization-free survival curve showed a
trend of improvement of G2-DES (92.0% vs. 93.8%, P = 0.082). These differences
diminished after PSM. Multivariate Cox proportional hazard regression analysis
showed a trend for G1-associated increase in revascularization (hazard ratio:
1.28, 95% confidence interval: 0.95-1.72, P = 0.099) while no significance was
found after PSM. Other endpoints showed no significant differences after
multivariate adjustment regardless of PSM. CONCLUSIONS: G1-DES showed the same
safety as G2-DES in this large Chinese cohort of real-world patients. However, G2
DES improved TLR-free survival of SCAD patients 2 years after PCI. The advantage
was influenced by baseline clinical factors. G1-DES was associated with a trend
of increase in revascularization risk and was not an independent predictor of
worse medium-term prognosis compared with G2-DES.
PMID- 28685715
TI - High Staphylococcus epidermidis Colonization and Impaired Permeability Barrier in
Facial Seborrheic Dermatitis.
AB - BACKGROUND: Seborrheic dermatitis (SD) is a common inflammatory skin condition.
The etiology is unclear, although overgrowth of Malassezia on the skin has been
suggested to cause SD. This study investigated whether colonization with
Staphylococcus plays a role in facial SD, which was not well addressed
previously. METHODS: The study was conducted from September 1, 2011 to February
20, 2012 in the First Hospital of China Medical University. In the first phase,
the study evaluated the level of transepidermal water loss (TEWL) and the number
of colony-forming units (CFU) of Staphylococcus in defined skin areas of SD
patients who were human immunodeficiency virus (HIV) seropositive (HIV [+] SD [+]
group, n = 13), classical SD (HIV [-] SD [+] group, n = 24) patients, HIV
seropositive-non-SD (HIV [+] SD [-] group, n = 16) patients, and healthy
volunteers (HIV [-] SD [-] group, n = 16). In the second phase, we enrolled
another cohort of HIV (-) SD (+) patients who applied topical fusidic acid (n =
15), tacrolimus (n = 16), or moisturizer (n = 12). Changes in the Seborrheic
Dermatitis Area Severity Index (SDASI), TEWL, and Staphylococcus density were
evaluated 2 weeks later. Comparisons of each index were performed using analysis
of variance (ANOVA) and least significant difference method. RESULTS: The level
of TEWL was greater through lesional sites in the HIV (+) SD (+) group than that
in HIV (+) SD (-) and HIV (-) SD (-) groups (95% confidence interval [CI]: 18.873
47.071, P < 0.001 and 95% CI: 28.755-55.936, P < 0.001, respectively). The number
of CFU of Staphylococcus was greater in the HIV (+) SD (+) group than that in HIV
(+) SD (-) and HIV (-) SD (-) groups (95% CI: 37.487-142.744, P = 0.001 and 95%
CI: 54.936-156.400, P < 0.001, respectively). TEWL was significantly more
improved in patients treated with tacrolimus and fusidic acid than that in those
treated with moisturizers (95% CI: 7.560-38.987, P = 0.004 and 95% CI: 4.659
37.619, P = 0.011, respectively). Topical tacrolimus and fusidic acid were
significantly associated with decreased SDASI as compared with moisturizer (95%
CI: 0.03-0.432, P = 0.025 and 95% CI: 0.033-0.44, P = 0.024, respectively).
CONCLUSIONS: High colonization with Staphylococcus epidermidis, along with
impaired skin permeability barrier function, contributes to the occurrence of SD.
PMID- 28685716
TI - Gene Variations of Sixth Complement Component Affecting Tacrolimus Metabolism in
Patients with Liver Transplantation for Hepatocellular Carcinoma.
AB - BACKGROUND: Orthotopic liver transplantation (OLT) improves the prognosis of
patients with hepatocellular carcinoma (HCC). Moreover, the complement system is
a powerful immune effector that can affect liver function and process of liver
cirrhosis. However, studies correlating the complement system with tacrolimus
metabolism after OLT are scarce. In this study, the role of single nucleotide
polymorphisms (SNPs) associated with the sixth complement component (C6) in
tacrolimus metabolism was investigated during the early stages of liver
transplantation. METHODS: The study enrolled 135 adult patients treated with OLT
for HCC between August 2011 and October 2013. Ten SNPs in C6 gene and rs776746 in
cytochrome P450 3A5 (CYP3A5) gene were investigated. The tacrolimus levels were
monitored daily during 4 weeks after transplantation. RESULTS: Both donor and
recipient CYP3A5 rs776746 allele A were correlated with decreased
concentration/dose (C/D) ratios. Recipient C6 rs9200 allele G and donor C6
rs10052999 homozygotes were correlated with lower C/D ratios. Recipient CYP3A5
rs776746 allele A (yielded median tacrolimus C/D ratios of 225.90 at week 1 and
123.61 at week 2), C6 rs9200 allele G (exhibited median tacrolimus C/D ratios of
211.31 at week 1, 110.23 at week 2, and 99.88 at week 3), and donor CYP3A5
rs776746 allele A (exhibited median C/D ratios of 210.82 at week 1, 111.06 at
week 2, 77.49 at week 3, and 85.60 at week 4) and C6 rs10052999 homozygote
(exhibited median C/D ratios of 167.59 at week 2, 157.99 at week 3, and 155.36 at
week 4) were associated with rapid tacrolimus metabolism. With increasing number
of these alleles, patients were found to have lower tacrolimus C/D ratios at
various time points during the 4 weeks after transplantation. In multiple linear
regression analysis, recipient C6 rs9200 group (AA vs. GG/GA) was found to be
related to tacrolimus metabolism at weeks 1, 2, and 3 (P = 0.005, P = 0.045, and
P = 0.033, respectively), whereas donor C6 rs10052999 group (CC/TT vs. TC) was
demonstrated to be correlated with tacrolimus metabolism only at week 4 (P =
0.001). CONCLUSIONS: Recipient C6 gene rs9200 polymorphism and donor C6 gene
rs10052999 polymorphism are new genetic loci that affect tacrolimus metabolism in
patients with HCC after OLT.
PMID- 28685717
TI - Variants in the Promoter Region of HLA-DQA1 were Associated with Idiopathic
Membranous Nephropathy in a Chinese Han Population.
AB - BACKGROUND: Idiopathic membranous nephropathy (IMN) is an autoimmune disease and
the leading cause of adult nephritic syndrome. HLA-DQA1 had been identified to be
associated with IMN in Europeans and the result was replicated in Chinese Han
population. In this study, six single nucleotide polymorphisms (SNPs) in the
promoter of HLA-DQA1 and other two SNPs with IgA nephropathy were included for
the association analysis. METHODS: The SNPs were genotyped in 509 patients and
601 controls by the MassArray iPLEX. The quantification of anti-phospholipase A2
receptor (PLA2R) antibodies in sera of IMN patients was performed by anti-PLA2R
ELISA (IgG) kit. RESULTS: After analysis, four SNPs were significantly associated
with IMN, with rs2187668 and rs28383345 as the top two signals (P = 8.42*10-5 and
2.48*10-5, respectively). Even under dominant model, the two SNPs were still
significantly associated with IMN (P = 3.50*10-3 for rs28383345 and P = 6.55*10-5
for rs2187668). After conditional study with rs2187668, rs28383345 was the only
variant significantly correlated with IMN after Bonferroni correction (P =
0.016). The minor alleles of the two SNPs were also mutually exclusive in our
cohort. This indicated that the two SNPs were independently associated with IMN
in Chinese Han population. Levels of anti-PLA2R autoantibodies were correlated
with the genotypes of the two SNPs, but not significantly (P>0.05). CONCLUSIONS:
Our results revealed that a novel independent variant in the promoter of HLA-DQA1
was associated with IMN in Chinese Han population. The locus possessed regulatory
role according to the data of RegulomeDB. The exact role of the SNPs on the
expression of HLA-DQA1 needs further investigation.
PMID- 28685718
TI - Clinical Characteristics, Electrophysiology, and Skin Biopsy of 38 Peripheral
Neuropathy Cases with Small Fiber Involvement of Various Etiologies.
AB - BACKGROUND: In small fiber neuropathy (SFN), thinly myelinated Adelta and
unmyelinated C fibers are primarily affected, resulting in sensory and/or
autonomic symptoms. Various etiologies have been shown to be associated with SFN.
This study was aimed to analyze a variety of features in peripheral neuropathy
(PN) with small fiber involvement, and to compare disease severity among patients
with idiopathic PN, PN associated with impaired glucose tolerance (IGT), and
metabolic syndrome (MS) PN. METHODS: Thirty-eight PN patients with small fiber
involvement were enrolled from December 20, 2013 to May 31, 2016. Patients were
divided into idiopathic PN, IGT-related PN, and MS-related PN groups. Detailed
medical history and small fiber neuropathy were investigated, and symptom
inventory questionnaire was conducted, as well as the visual analog scale. Nerve
conduction studies and skin biopsies were also performed. The differences among
the groups were analyzed using analysis of variance and Kruskal-Wallis test.
RESULTS: Eight patients were diagnosed with pure SFN. Intraepidermal nerve fiber
density (IENFD) weakly correlated with motor conduction velocity (MCV) (r =
0.372, P = 0.025), and proximal (r = 0.383, P = 0.021) and distal (r = 0.358, P =
0.032) compound muscle action potential (CMAP) of the tibial nerve. IENFD also
weakly correlated with MCV of the peroneal nerve (r = 0.399, P = 0.016). IENFD
was shown to be significantly different among all groups (chi2 = 9.901, P =
0.007). IENFD was significantly decreased (chi2 = 23.000, P = 0.003) in the MS
related PN group compared to the idiopathic PN group. The MCV of the tibial nerve
was significantly different among all groups (chi2 = 8.172, P < 0.017). The
proximal (F = 4.336, P = 0.021) and distal (F = 3.262, P = 0.049) CMAP of the
tibial nerve was also significantly different among all groups. CONCLUSIONS:
IENFD of patients included in the present study weakly correlated with various
electrophysiological parameters. Small and large fibers are more involved in
patients with MS-related PN than in patients with idiopathic PN.
PMID- 28685719
TI - Motivations and Training Needs of General Practitioner Preceptors.
AB - BACKGROUND: General practitioner (GP) preceptors play an important role in the
cultivation of GPs. Many problems exist in the training of GP preceptors. This
study aimed to explore the willingness and training needs of GP preceptors and
compare the differences between preceptors from general practice and other
specialties. METHODS: A total of 375 questionnaire forms were sent to 375 GP
preceptors from 11 different provinces, and 344 completed forms were returned.
The main outcome included general information, teaching motivations, and training
needs of GP preceptors. RESULTS: The study showed that about 89.2% of GP
preceptors were willing to be teachers. The majority of respondents strongly
agreed that the motivation for becoming a GP supervisor was to learn from
teaching. The most important capability they should master was clinical teaching
(92.2%), followed by lecture (83.1%) and doctor-patient communication (83.1%).
The top three preferred methods of GP preceptors training were case discussion
(78.8%), workshop (57.6%), and classroom teaching (56.4%). The domains in which
most GP preceptors wanted to acquire knowledge and skill were mental health
(59.3%), rehabilitation (47.1%), pediatrics (41.0%), and obstetrics (37.5%). No
significant differences were found in the willingness to train GPs (chi2 = 3.34,
P > 0.05) and whether they would become or continue to become a GP supervisor
after the training (chi2 = 1.106, P > 0.05). CONCLUSIONS: Although most
preceptors were under on-the-job training, they were glad to train GPs. To be
qualified, preceptors should be trained according to the actual needs of GP
preceptors.
PMID- 28685720
TI - Effect of Platelet-derived P-selectin on Neutrophil Recruitment in a Mouse Model
of Sepsis-induced Acute Kidney Injury.
AB - BACKGROUND: Acute kidney injury (AKI) is a severe disease in critically ill
patients. Neutrophil infiltration into kidney was associated with the development
of AKI, and P-selectin may be involved in the process of neutrophil recruitment
in kidney. This study aimed to explore the potential effect of platelet-derived P
selectin on neutrophil recruitment in a mouse model of sepsis-induced AKI.
METHODS: A total of 30 C57BL/6 male mice were divided into five groups (n = 6 in
each): sham group, sepsis group, anti-Ly6G group, anti-P-selectin group, and
platelet depletion group. Sepsis was induced by cecal ligation and puncture.
Serum creatinine concentration and platelet activity were measured by biochemical
detector and flow cytometry, respectively. Histological and pathological features
were analyzed using hematoxylin-eosin (H&E) and immunohistochemistry (IHC)
staining, respectively. Myeloperoxidase (MPO) activity was detected with MPO
assay. Unpaired t-test was used for data analysis. RESULTS: Serum creatinine
increased significantly in septic group compared to sham group (2.68 +/- 0.27
mg/dl vs. 0.82 +/- 0.19 mg/dl, t = 12.06, P = 0.0000) but attenuated in
antibodies-treated animals compared to septic group (anti-Ly6G: 1.62 +/- 0.30
mg/dl vs. 2.68 +/- 0.27 mg/dl, t = 5.76, P = 0.0004; anti-P-selectin: 1.76 +/-
0.31 mg/dl vs. 2.68 +/- 0.27 mg/dl, t = 4.92, P = 0.0012; and platelet depletion:
1.93 +/- 0.29 mg/dl vs. 2.68 +/- 0.27 mg/dl, t = 4.14, P = 0.0032). Platelet
amount significantly decreased compared to sham group (658.20 +/- 60.64 * 109/L
vs. 822.00 +/- 48.60 * 109/L, t = 4.71, P = 0.0015) in septic mice, especially in
platelet depletion group (240.80 +/- 44.98 * 109/L vs. 822.00 +/- 48.60 * 109/L,
t = 19.63, P = 0.0000). P-selectin activity was significantly increased in septic
group compared to sham group (16.54 +/- 1.60% vs. 1.90 +/- 0.29%, t = 15.64, P =
0.0000) but decreased significantly in platelet depletion group compared to
septic group (3.62 +/- 0.68% vs. 16.54 +/- 1.60%, t = 12.89, P = 0.0002). IHC
analysis shown that neutrophil infiltration increased in septic mice compared to
sham group (36.67 +/- 3.79% vs. 9.17 +/- 1.61%, t = 11.58, P = 0.0003) and
function-blocked groups (anti-Ly6G: 36.67 +/- 3.79% vs. 15.33 +/- 1.53%, t =
9.05, P = 0.0008; anti-P-selectin: 36.67 +/- 3.79% vs. 21.33 +/- 1.53%, t = 6.51,
P = 0.0029; and platelet depletion: 36.67 +/- 3.79% vs. 23.33 +/- 3.06%, t =
4.75, P = 0.0090). MPO increased significantly in septic group compared to
control (49.73 +/- 1.83 ng/mg prot vs. 13.04 +/- 2.16 ng/mg prot, t = 19.03, P =
0.0000) but decreased in function-blocked groups compared to septic group (anti
Ly6G: 26.52 +/- 3.86 ng/mg prot vs. 49.73 +/- 1.83 ng/mg prot, t = 9.59, P =
0.0000; anti-P-selectin: 33.06 +/- 6.75 ng/mg prot vs. 49.73 +/- 1.83 ng/mg prot,
t = 4.85, P = 0.0013; and platelet depletion: 33.37 +/- 2.25 ng/mg prot vs. 49.73
+/- 1.83 ng/mg prot, t = 5.33, P = 0.0007). CONCLUSION: Platelets-derived P
selectin may be involved in the development of septic AKI through inducing
neutrophil infiltration into kidney.
PMID- 28685721
TI - Antiapoptotic Effect of Gene Therapy with Recombinant Adenovirus Vector
Containing Hypoxia-inducible Factor-1alpha after Cerebral Ischemia and
Reperfusion in Rats.
AB - BACKGROUND: Mounting evidence has demonstrated that hypoxia-inducible factor
1alpha (HIF-1alpha) could attenuate brain injuries after cerebral ischemia and
reperfusion (CIR). However, few reports have addressed the therapeutic efficacies
of a recombinant adenovirus vector containing HIF-1alpha (AdHIF-1alpha) gene
after ischemia and reperfusion. The aim of this study was to examine the
antiapoptotic and neuroprotective effects of AdHIF-1alpha gene for cerebral
injuries after ischemia and reperfusion in rats. METHODS: From February to
December 2016, male Sprague-Dawley rats were randomly divided into normal, sham,
CIR, AdHIF-1alpha, and recombinant adenovirus (Ad) groups. Middle cerebral artery
occlusion model was established by Longa's method and reperfusion resumed at 2 h
postocclusion. AdHIF-1alpha solution, Ad solution, and phosphate-buffered saline
were injected into the right lateral ventricle of rats in AdHIF-1alpha, Ad, and
CIR groups. Brain tissue sections were observed under fluorescent microscope to
confirm the definite expression of recombinant adenovirus in Ad and AdHIF-1alpha
groups. The expressions of HIF-1alpha protein were analyzed by
immunohistochemical staining at 6 h, 24 h, and 72 h postreperfusion. Brain water
content and neurological deficit scores were evaluated at 6 h, 24 h, and 72 h
postreperfusion. Pathological brain injuries were examined after hematoxylin and
eosin stain and nerve cell apoptosis was measured after terminal-deoxynucleotidyl
transferase-mediated dUTP-biotin nick end labeling (TUNEL) stain at 72 h
postreperfusion. Comparisons were conducted with one-way analysis of variance by
post hoc Scheffe's test among different experimental groups. RESULTS: Green
fluorescent protein was successfully expressed in brain tissue of Ad and AdHIF
1alpha groups from 24 h to 21 days postinjection. As detected by
immunohistochemical staining, the expressions of HIF-1alpha protein were
obviously enhanced in AdHIF-1alpha group than those in CIR and Ad groups at 24 h
and 72 h postreperfusion, respectively. There were significant reductions of
brain water content (78.83% +/- 0.34% vs. 83.21% +/- 0.50% and 83.35% +/- 0.32%;
84.13% +/- 0.24% vs. 89.76% +/- 0.34% and 89.70% +/- 0.18%; respectively; all P <
0.05) and neurological deficit scores (2.90 +/- 0.74 vs. 3.50 +/- 0.52 and 3.60
+/- 0.53 at 24 h; 2.40 +/- 0.84 vs. 3.60 +/- 0.52 and 3.50 +/- 0.53 at 72 h;
respectively; all P < 0.05) in AdHIF-1alpha group versus CIR and Ad groups at 24
h and 72 h postreperfusion, respectively. The pathologic changes of AdHIF-1alpha
group were milder than those in CIR and Ad groups at 72 h postreperfusion. The
percentage of TUNEL-positive cells in cerebral subcortex decreased significantly
in AdHIF-1alpha group versus CIR and Ad groups at 72 h postreperfusion (P <
0.05). CONCLUSION: AdHIF-1alpha has an obvious neuroprotective effect on ischemia
and reperfusion in rat brains possibly through inhibiting the apoptosis of nerve
cells.
PMID- 28685722
TI - Can Dexmedetomidine Improve Arterial Oxygenation and Intrapulmonary Shunt during
One-lung Ventilation in Adults Undergoing Thoracic Surgery? A Meta-analysis of
Randomized, Placebo-controlled Trials.
AB - BACKGROUND: One-lung ventilation (OLV) is a common ventilation technology during
thoracic surgery that can cause serious clinical problems. We aimed to conduct a
meta-analysis to compare oxygenation and intrapulmonary shunt during OLV in
adults undergoing thoracic surgery with dexmedetomidine (Dex) versus placebo to
assess the influence and safety of using Dex. METHODS: Randomized controlled
trials comparing lung protection in patients who underwent thoracic surgery with
Dex or a placebo were retrieved from PubMed, EMBASE, MEDLINE, Cochrane Library,
and China CNKI database. The following information was extracted from the paper:
arterial oxygen partial pressure (PaO2), PaO2/inspired oxygen concentration
(PaO2/FiO2, oxygenation index [OI]), intrapulmonary shunt (calculated as Qs/Qt),
mean arterial pressure (MAP), heart rate (HR), tumor necrosis factor-alpha (TNF
alpha), interleukin (IL)-6, superoxide dismutase (SOD), and malondialdehyde
(MDA). RESULTS: Fourteen randomized controlled trials were included containing a
total of 625 patients. Compared with placebo group, Dex significantly increased
PaO2/FiO2(standard mean difference [SMD] = 0.98, 95% confidence interval [CI]
[0.72, 1.23], P < 0.00001). Besides, Qs/Qt (SMD= -1.22, 95% CI [-2.20, -0.23], P
= 0.020), HR (SMD= -0.69, 95% CI [-1.20, 0.17], P = 0.009), MAP (SMD= -0.44, 95%
CI [-0.84, 0.04], P = 0.030), the concentrations of TNF-alpha (SMD = -1.55, 95%
CI [-2.16, -0.95], P <0.001), and IL-6 (SMD = -1.53, 95% CI [-2.37, -0.70], P =
0.0003) were decreased in the treated group, when compared to placebo group. No
significant difference was found in MDA (SMD = -1.14, 95% CI [-3.48, 1.20], P =
0.340) and SOD (SMD = 0.41, 95% CI [-0.29, 1.10], P = 0.250) between the Dex
group and the placebo group. Funnel plots did not detect any significant
publication bias. CONCLUSIONS: Dex may improve OI and reduce intrapulmonary shunt
during OLV in adults undergoing thoracic surgery. However, this conclusion might
be weakened by the limited number of pooled studies and patients.
PMID- 28685723
TI - Radiation Therapy in Keloids Treatment: History, Strategy, Effectiveness, and
Complication.
AB - OBJECTIVE: Radiation therapy combined with surgical excision was considered as
one of the most effective treatment plans for keloid lesions. However, there was
no unanimity found over present literatures regarding the issue on optimized
treatment strategy for keloids. We here provide a comprehensive review over this
issue and emphasize on the influencing factors. DATA SOURCES: The data analyzed
in this review were searched from articles included in PubMed and EMBASE
databases. STUDY SELECTION: The original articles and critical reviews discussing
the application of radiation therapy in keloids treatment were selected for this
review. RESULTS: The application of radiation therapy has transitioned from
simple superficial X-ray irradiation to brachytherapy. Furthermore, several
factors including radiation type, dose, fraction, interval, and complications
were reviewed, and the results revealed that these factors were significant
toward clinical outcome at various levels. CONCLUSIONS: Both past and present
evidence support the idea that combination therapy of radiation and surgical
therapy is safe and feasible. However, the optimization of treatment strategy was
based on different radiation types and should take dose, fractions, interval, and
complications into consideration, which will then decrease the rate of recurrence
and increase the level of satisfaction.
PMID- 28685725
TI - Origin and Prevention of Workplace Violence in Health Care in China: Legal and
Ethical Considerations.
PMID- 28685724
TI - Role of Contrast-enhanced Ultrasound in the Evaluation of Inflammatory Arthritis.
AB - OBJECTIVE: Contrast-enhanced ultrasound (CEUS) is a well-established imaging
modality which has been put into clinical use in recent years with the
development of second-generation contrast agent and imaging devices, and its
applications in the assessment of inflammatory arthritis, such as rheumatoid
arthritis, psoriatic arthritis, and ankylosing spondylitis, have provoked
abundant discussion and researches among radiologists and rheumatologists. To
summarize the achievements of clinical studies on CEUS in the application of
arthritis, and to keep up with the latest progresses of the imaging technique, we
reviewed the literature in recent years, hoping to establish the role of CEUS in
joint diseases. DATA SOURCES: PubMed and EMBASE. STUDY SELECTION: We searched the
database with the conditions "contrast-enhanced ultrasound AND arthritis" with
the time limitation of recent 10 years. Clinical studies applying CEUS in
inflammatory arthritis and review articles about development of CEUS in joint
diseases in English were selected. RESULTS: As it is proved by most studies in
recent years, by delineating microvasculature within the inflamed joints, CEUS
can indicate early arthritis with high sensitivity and specificity. Moreover, the
imaging of CEUS has been proved to be consistent with histopathological changes
of inflammatory arthritis. Quantitative analysis of CEUS permits further
evaluation of disease activity. CEUS also plays a significant role in the
therapeutic monitoring of the disease, which has been backed up by a number of
studies. CONCLUSIONS: CEUS may be a new choice for the rheumatologists to
evaluate inflammatory arthritis, because of its low price, ability to provide
dynamic pictures, and high sensitivity to angiogenesis. It can also be applied in
disease classification and therapeutic monitoring. More studies about CEUS need
to be done to set up the diagnostic standards.
PMID- 28685726
TI - Surgical Treatment of Large Left Ventricular Fibroma in Children.
PMID- 28685727
TI - Subscapular Bursa: Anatomy and Magnetic Resonance Appearance.
PMID- 28685728
TI - Effects of Intraorbital Electroacupuncture on Diabetic Abducens Nerve Palsy.
PMID- 28685729
TI - Biomechanical Properties of Synthetic Mesh Reconstructed Glenohumeral Joint
Capsule.
PMID- 28685730
TI - Effect of Closed Suctioning on Reducing the Contamination Released into the
Environment.
PMID- 28685731
TI - Dermoscopic Features and Gene Mutation in the Mevalonate Pathway of Five Sporadic
Patients with Porokeratosis.
PMID- 28685732
TI - Effect and Safety of Peroral Endoscopic Cardial Constriction for Gastroesophageal
Reflux Disease.
PMID- 28685733
TI - Treatment for 15 Cases of Cervical Tuberculosis.
PMID- 28685734
TI - Ultrasound-guided Removal of Retained Soft Tissue Foreign Body with Late
Presentation.
PMID- 28685735
TI - Hidradenocarcinoma of the Dorsum of the Hand.
PMID- 28685736
TI - Pemetrexed-associated Ischemic Colitis in Nonsmall Cell Lung Cancer.
PMID- 28685737
TI - Sclerotic Liposarcoma in the Deep Temporal Space of a 7-year-old Child.
PMID- 28685738
TI - Local Anesthetic Lidocaine for Gastroscopy Induces Diffuse Alveolar Hemorrhage.
PMID- 28685739
TI - Epibulbar Osseous Choristoma in the Lateral Rectus.
PMID- 28685740
TI - Gastric Kaposi's sarcoma simulating gastric lymphoma during endoscopic ultrasound
examination.
PMID- 28685741
TI - New curved linear echoendoscope for endoscopic ultrasonography-guided fine-needle
aspiration in patients with Roux-en-Y reconstruction (with videos).
PMID- 28685742
TI - The value of endoscopic ultrasound-fine needle aspiration in the suspicion of
pancreatic hydatid cyst in endemic areas with negative serology (with video).
PMID- 28685743
TI - Stent drainage achieved by endoscopic ultrasonography-guided puncture from
duodenal bulb to the minor pancreatic duct for the treatment of acute epigastric
pain in a patient with pancreas divisum.
PMID- 28685744
TI - Endorectal fusion imaging: A description of a new technique.
AB - BACKGROUND: Fusion imaging is an accepted method in abdominal imaging allowing a
simultaneous display of reference imaging with a live ultrasound (US)
investigation. For prostate cancer, promising results have been published for
endorectal US (ERUS)-guided biopsy of suspicious lesions in magnetic resonance
imaging (MRI). To our knowledge, no other indication for the fusion of ERUS with
MRI has been reported so far. METHODS: We report on three patients scheduled for
ERUS due to anorectal fistulae after treatment (n = 2) or rectal carcinoma (n =
1), which were scheduled for real-time virtual onography (RVS), a method for the
fusion of MRI imaging with US. RESULTS: In all patients, RVS was successful. The
course of the fistulae could be defined and the success of the treatment could be
confirmed. In the patient with rectal carcinoma, the lymph nodes suspicious in
MRI could be identified. CONCLUSIONS: MRI/ERUS fusion has the potential for
follow-up of anorectal fistulae and abscesses, and staging of anal and rectal
tumors.
PMID- 28685745
TI - Use of partially covered and uncovered metallic prosthesis for endoscopic
ultrasound-guided hepaticogastrostomy: Results of a retrospective monocentric
study.
AB - BACKGROUND AND OBJECTIVES: Endoscopic ultrasound-guided hepaticogastrostomy (EUS
HGS) represents an option to treat obstructive jaundice when endoscopic
retrograde cholangiopancreatography (ERCP) fails. The success rate of this
procedure has been shown to be very high. Up to now, plastic and self-expandable
metallic stents (SEMSs) have been employed, each of them presenting some
limitations. The aims of this study were to evaluate the technical and functional
success rates of EUS-HGS using a dedicated biliary SEMS with a half-covered part
(Giobor(r) stent). METHODS: We retrospectively reviewed data of patients, who
underwent EUS-HGS at our center, with at least 6 months of follow-up.
Demographic, clinical, and laboratory data were extracted from the patient's
charts and electronic records. Technical success rate was defined as the
successful passage of the Giobor stent across the stomach, along with the flow of
contrast medium and/or bile through the stent. Functional success rate was
considered achieved when the decrease of bilirubin value of at least 25% within
the 1st week was obtained. The rate of early and late complications was assessed.
RESULTS: A total of 41 patients were included (21F/20M, [mean age 66, range 45
85]). Technical success rate was obtained in 37 (90.2%) of patients. Functional
success rate, analyzable in 29 patients, occurred in 65%. Between the 37 patients
in whom HGS was technically feasible, 13 patients (31.7%) presented an early
complication, mostly infective. At 6-month follow-up, 10/37 patients (27.0%)
required a new biliary drainage (BD) and 11/37 (29.7%) died because of their
disease. CONCLUSIONS: EUS-HGS using Giobor(r) stent is technically feasible,
clinical effective, safe, and may be an alternative to percutaneous transhepatic
BD in case of ERCP failure for biliary decompression.
PMID- 28685746
TI - Significance of normal appearance on endoscopic ultrasonography in the diagnosis
of early chronic pancreatitis.
AB - Background and Objectives: The Rosemont classification (RC) was developed as a
consensus-based standard for the diagnosis of chronic pancreatitis (CP) by
endoscopic ultrasonography (EUS), however, it is more complicated than the
conventional scoring system. We have noticed that in the early stages of CP, it
is not unusual to observe pancreas with abnormal appearance coexisting with the
areas of normal parenchyma. The aim of this study was to investigate the validity
of a "normal" pancreas appearance and to evaluate the usefulness of modified
diagnostic criteria in comparison to the traditional EUS criteria and the RC.
Patients and Methods: One hundred and seventy-seven patients who had undergone
both EUS and endoscopic retrograde pancreatography (ERP) within 2 months were
enrolled in the study, and patients with pancreatic cancer were excluded from the
study. ERP findings were used as the gold standard for the diagnosis of CP. The
EUS images obtained were classified according to both the RC and our new modified
criteria. The latter includes an additional criterion to the modified traditional
criteria: fine-reticular pattern (F-RP) was defined as a normal pancreatic
parenchyma. We compared the accuracy between the new modified EUS criteria and
the RC. Results: (1) Normal or equivocal findings on ERP were obtained for 132
patients; 113 patients had F-RP on EUS. In contrast, F-RP was found in only 6 out
of 45 CP cases on ERP (P < 0.0001). (2) We investigated the diagnostic capability
of our new criteria for endoscopic retrograde cholangiopancreatography
normal/equivocal pancreas compared to the traditional criteria. In cases where
fewer than two points were defined as normal, the incidence of normal pancreas
was significantly higher based on the new criteria than on the traditional
criteria (P = 0.002). (3) No significant differences were found between the new
criteria and the RC across all ERP grades. Conclusion: Our new proposed "normal
added EUS criteria" for diagnosing CP was equivalent to the RC.
PMID- 28685747
TI - Assessing tumor angiogenesis in colorectal cancer by quantitative contrast
enhanced endoscopic ultrasound and molecular and immunohistochemical analysis.
AB - Background and Objectives: Data on contrast-enhanced endoscopic ultrasound (CE
EUS) for colorectal cancer (CRC) evaluation are scarce. Therefore, we aimed to
assess the vascular perfusion pattern in CRC by quantitative CE-EUS and compare
it to immunohistochemical and genetic markers of angiogenesis. Patients and
Methods: We performed a retrospective analysis of CE-EUS examinations of 42 CRC
patients, before any therapy. CE-EUS movies were processed using a dedicated
software. Ten parameters were automatically generated from the time-intensity
curve (TIC) analysis: peak enhancement (PE), rise time (RT), mean transit time,
time to peak (TTP), wash-in area under the curve (WiAUC), wash-in rate (WiR),
wash-in perfusion index (WiPI), wash-out AUC (WoAUC), and wash-in and wash-out
AUC (WiWoAUC). The expression levels of the vascular endothelial growth factor
receptor 1 (VEGFR1) and VEGFR2 genes were assessed from biopsy samples harvested
during colonoscopy. Microvascular density and vascular area were calculated after
CD31 and CD105 immunostaining. Results: Forty-two CE-EUS video sequences were
analyzed. We found positive correlations between the parameters PE, WiAUC, WiR,
WiPI, WoAUC, WiWoAUC, and N staging (Spearman r = 0.437, r = 0.336, r = 0.462, r
= 0.437, r = 0.358, and r = 0.378, respectively, P < 0.05), and also between RT
and TTP and CD31 vascular area (r = 0.415, and r = 0.421, respectively, P <
0.05). VEGFR1 and VEGFR2 expression did not correlate with any of the TIC
parameters. Conclusions: CE-EUS with TIC analysis enables minimally invasive
assessment of CRC angiogenesis and may provide information regarding the lymph
nodes invasion. However, further studies are needed for defining its role in the
evaluation of CRC patients.
PMID- 28685748
TI - Achievement of long-term stent patency in endoscopic ultrasonography-guided right
bile duct drainage after left hepatic lobectomy (with video).
PMID- 28685749
TI - The E3 ubiquitin ligase and RNA-binding protein ZNF598 orchestrates ribosome
quality control of premature polyadenylated mRNAs.
AB - Cryptic polyadenylation within coding sequences (CDS) triggers ribosome
associated quality control (RQC), followed by degradation of the aberrant mRNA
and polypeptide, ribosome disassembly and recycling. Although ribosomal subunit
dissociation and nascent peptide degradation are well-understood, the molecular
sensors of aberrant mRNAs and their mechanism of action remain unknown. We
studied the Zinc Finger Protein 598 (ZNF598) using PAR-CLIP and revealed that it
cross-links to tRNAs, mRNAs and rRNAs, thereby placing the protein on translating
ribosomes. Cross-linked reads originating from AAA-decoding tRNALys(UUU) were 10
fold enriched over its cellular abundance, and poly-lysine encoded by poly(AAA)
induced RQC in a ZNF598-dependent manner. Encounter with translated polyA
segments by ZNF598 triggered ubiquitination of several ribosomal proteins,
requiring the E2 ubiquitin ligase UBE2D3 to initiate RQC. Considering that human
CDS are devoid of >4 consecutive AAA codons, sensing of prematurely placed polyA
tails by a specialized RNA-binding protein is a novel nucleic-acid-based
surveillance mechanism of RQC.
PMID- 28685751
TI - Meniscus-assisted solution printing of large-grained perovskite films for high
efficiency solar cells.
AB - Control over morphology and crystallinity of metal halide perovskite films is of
key importance to enable high-performance optoelectronics. However, this remains
particularly challenging for solution-printed devices due to the complex
crystallization kinetics of semiconductor materials within dynamic flow of inks.
Here we report a simple yet effective meniscus-assisted solution printing (MASP)
strategy to yield large-grained dense perovskite film with good crystallization
and preferred orientation. Intriguingly, the outward convective flow triggered by
fast solvent evaporation at the edge of the meniscus ink imparts the transport of
perovskite solutes, thus facilitating the growth of micrometre-scale perovskite
grains. The growth kinetics of perovskite crystals is scrutinized by in situ
optical microscopy tracking to understand the crystallization mechanism. The
perovskite films produced by MASP exhibit excellent optoelectronic properties
with efficiencies approaching 20% in planar perovskite solar cells. This robust
MASP strategy may in principle be easily extended to craft other solution-printed
perovskite-based optoelectronics.
PMID- 28685750
TI - MiR-497~195 cluster regulates angiogenesis during coupling with osteogenesis by
maintaining endothelial Notch and HIF-1alpha activity.
AB - A specific bone vessel subtype, strongly positive for CD31 and endomucin
(CD31hiEmcnhi), is identified as coupling angiogenesis and osteogenesis. The
abundance of type CD31hiEmcnhi vessels decrease during ageing. Here we show that
expression of the miR-497~195 cluster is high in CD31hiEmcnhi endothelium but
gradually decreases during ageing. Mice with depletion of miR-497~195 in
endothelial cells show fewer CD31hiEmcnhi vessels and lower bone mass.
Conversely, transgenic overexpression of miR-497~195 in murine endothelium
alleviates age-related reduction of type CD31hiEmcnhi vessels and bone loss. miR
497~195 cluster maintains the endothelial Notch activity and HIF-1alpha stability
via targeting F-box and WD-40 domain protein (Fbxw7) and Prolyl 4-hydroxylase
possessing a transmembrane domain (P4HTM) respectively. Notably, endothelialium
specific activation of miR-195 by intravenous injection of aptamer-agomiR-195
stimulates CD31hiEmcnhi vessel and bone formation in aged mice. Together, our
study indicates that miR-497~195 regulates angiogenesis coupled with osteogenesis
and may represent a potential therapeutic target for age-related osteoporosis.
PMID- 28685752
TI - Understanding extreme sea levels for broad-scale coastal impact and adaptation
analysis.
AB - One of the main consequences of mean sea level rise (SLR) on human settlements is
an increase in flood risk due to an increase in the intensity and frequency of
extreme sea levels (ESL). While substantial research efforts are directed towards
quantifying projections and uncertainties of future global and regional SLR,
corresponding uncertainties in contemporary ESL have not been assessed and
projections are limited. Here we quantify, for the first time at global scale,
the uncertainties in present-day ESL estimates, which have by default been
ignored in broad-scale sea-level rise impact assessments to date. ESL
uncertainties exceed those from global SLR projections and, assuming that we meet
the Paris agreement goals, the projected SLR itself by the end of the century in
many regions. Both uncertainties in SLR projections and ESL estimates need to be
understood and combined to fully assess potential impacts and adaptation needs.
PMID- 28685753
TI - Nucleolin directly mediates Epstein-Barr virus immune evasion through binding to
G-quadruplexes of EBNA1 mRNA.
AB - The oncogenic Epstein-Barr virus (EBV) evades the immune system but has an
Achilles heel: its genome maintenance protein EBNA1, which is essential for viral
genome maintenance but highly antigenic. EBV has seemingly evolved a system in
which the mRNA sequence encoding the glycine-alanine repeats (GAr) of the EBNA1
protein limits its expression to the minimal level necessary for function while
minimizing immune recognition. Here, we identify nucleolin (NCL) as a host factor
required for this process via a direct interaction with G-quadruplexes formed in
GAr-encoding mRNA sequence. Overexpression of NCL enhances GAr-based inhibition
of EBNA1 protein expression, whereas its downregulation relieves the suppression
of both expression and antigen presentation. Moreover, the G-quadruplex ligand
PhenDC3 prevents NCL binding to EBNA1 mRNA and reverses GAr-mediated repression
of EBNA1 expression and antigen presentation. Hence the NCL-EBNA1 mRNA
interaction is a relevant therapeutic target to trigger an immune response
against EBV-carrying cancers.
PMID- 28685755
TI - Nonlinear cavity optomechanics with nanomechanical thermal fluctuations.
AB - Although the interaction between light and motion in cavity optomechanical
systems is inherently nonlinear, experimental demonstrations to date have allowed
a linearized description in all except highly driven cases. Here, we demonstrate
a nanoscale optomechanical system in which the interaction between light and
motion is so large (single-photon cooperativity C0~103) that thermal motion
induces optical frequency fluctuations larger than the intrinsic optical
linewidth. The system thereby operates in a fully nonlinear regime, which
pronouncedly impacts the optical response, displacement measurement and radiation
pressure backaction. Specifically, we measure an apparent optical linewidth that
is dominated by thermo-mechanically induced frequency fluctuations over a wide
temperature range, and show that in this regime thermal displacement measurements
cannot be described by conventional analytical models. We perform a proof-of
concept demonstration of exploiting the nonlinearity to conduct sensitive
quadratic readout of nanomechanical displacement. Finally, we explore how
backaction in this regime affects the mechanical fluctuation spectra.
PMID- 28685754
TI - Collagen-derived proline promotes pancreatic ductal adenocarcinoma cell survival
under nutrient limited conditions.
AB - Tissue architecture contributes to pancreatic ductal adenocarcinoma (PDAC)
phenotypes. Cancer cells within PDAC form gland-like structures embedded in a
collagen-rich meshwork where nutrients and oxygen are scarce. Altered metabolism
is needed for tumour cells to survive in this environment, but the metabolic
modifications that allow PDAC cells to endure these conditions are incompletely
understood. Here we demonstrate that collagen serves as a proline reservoir for
PDAC cells to use as a nutrient source when other fuels are limited. We show PDAC
cells are able to take up collagen fragments, which can promote PDAC cell
survival under nutrient limited conditions, and that collagen-derived proline
contributes to PDAC cell metabolism. Finally, we show that proline oxidase
(PRODH1) is required for PDAC cell proliferation in vitro and in vivo.
Collectively, our results indicate that PDAC extracellular matrix represents a
nutrient reservoir for tumour cells highlighting the metabolic flexibility of
this cancer.
PMID- 28685759
TI - Parkinson disease: Defining PD subtypes - a step toward personalized management?
PMID- 28685756
TI - The Role of the Endocannabinoid System and Genetic Variation in Adolescent Brain
Development.
AB - During adolescence, both rodent and human studies have revealed dynamic changes
in the developmental trajectories of corticolimbic structures, which are known to
contribute to the regulation of fear and anxiety-related behaviors. The
endocannabinoid (eCB) system critically regulates stress responsivity and anxiety
throughout the life span. Emerging evidence suggests that during adolescence,
changes in eCB signaling contribute to the maturation of local and corticolimbic
circuit populations of neurons, such as mediating the balance between excitatory
and inhibitory neurotransmission within the prefrontal cortex. This function of
the eCB system facilitates efficient communication within and between brain
regions and serves a central role in establishing complex and adaptive cognitive
and behavioral processing. Although these peri-adolescent changes in eCB
signaling promote brain development and plasticity, they also render this period
a particularly sensitive one for environmental perturbations to these normative
fluctuations in eCB signaling, such as stress, potentially leading to altered
developmental trajectories of neural circuits governing emotional behaviors. In
this review, we focus on the role of eCB signaling on the regulation of stress
and anxiety-related behaviors both during and after adolescence. Moreover, we
discuss the functional implications of human genetic variation in the eCB system
for the risk for anxiety and consequences of stress across development and into
adulthood.
PMID- 28685757
TI - Social Learning Requires Plasticity Enhanced by Fluoxetine Through Prefrontal
Bdnf-TrkB Signaling to Limit Aggression Induced by Post-Weaning Social Isolation.
AB - Escalated or abnormal aggression induced by early adverse experiences is a
growing issue of social concern and urges the development of effective treatment
strategies. Here we report that synergistic interactions between psychosocial and
biological factors specifically ameliorate escalated aggression induced by early
adverse experiences. Rats reared in isolation from weaning until early adulthood
showed abnormal forms of aggression and social deficits that were temporarily
ameliorated by re-socialization, but aggression again escalated in a novel
environment. We demonstrate that when re-socialization was combined with the
antidepressant fluoxetine, which has been shown to reactivate juvenile-like state
of plasticity, escalated aggression was greatly attenuated, while neither
treatment alone was effective. Early isolation induced a permanent, re
socialization-resistant reduction in Bdnf expression in the amygdala and the
infralimbic cortex. Only the combined treatment of fluoxetine and re
socialization was able to recover Bdnf expression via epigenetic regulation.
Moreover, the behavior improvement after the combined treatment was dependent on
TrkB activity. Combined treatment specifically strengthened the input from the
ventral hippocampus to the mPFC, suggesting that this pathway is an important
mediator of the beneficial behavioral effects of the combined psychosocial and
pharmacological treatment of abnormal aggression. Our findings suggest that
synergy between pharmacological induction of plasticity and psychosocial
rehabilitation could enhance the efficacy of therapies for pathological
aggression.
PMID- 28685758
TI - Greening of the Sahara suppressed ENSO activity during the mid-Holocene.
AB - The evolution of the El Nino-Southern Oscillation (ENSO) during the Holocene
remains uncertain. In particular, a host of new paleoclimate records suggest that
ENSO internal variability or other external forcings may have dwarfed the fairly
modest ENSO response to precessional insolation changes simulated in climate
models. Here, using fully coupled ocean-atmosphere model simulations, we show
that accounting for a vegetated and less dusty Sahara during the mid-Holocene
relative to preindustrial climate can reduce ENSO variability by 25%, more than
twice the decrease obtained using orbital forcing alone. We identify changes in
tropical Atlantic mean state and variability caused by the momentous
strengthening of the West Africa Monsoon (WAM) as critical factors in amplifying
ENSO's response to insolation forcing through changes in the Walker circulation.
Our results thus suggest that potential changes in the WAM due to anthropogenic
warming may influence ENSO variability in the future as well.
PMID- 28685760
TI - Prion disease: 'Anti-prions' block prion disease onset.
PMID- 28685763
TI - What is the right amount to spend on biopharma R&D?
PMID- 28685764
TI - Market watch: Strategies for biosimilars in emerging markets.
PMID- 28685765
TI - Western tropical Pacific multidecadal variability forced by the Atlantic
multidecadal oscillation.
AB - Observational analysis suggests that the western tropical Pacific (WTP) sea
surface temperature (SST) shows predominant variability over multidecadal time
scales, which is unlikely to be explained by the Interdecadal Pacific
Oscillation. Here we show that this variability is largely explained by the
remote Atlantic multidecadal oscillation (AMO). A suite of Atlantic Pacemaker
experiments successfully reproduces the WTP multidecadal variability and the AMO
WTP SST connection. The AMO warm SST anomaly generates an atmospheric
teleconnection to the North Pacific, which weakens the Aleutian low and
subtropical North Pacific westerlies. The wind changes induce a subtropical North
Pacific SST warming through wind-evaporation-SST effect, and in response to this
warming, the surface winds converge towards the subtropical North Pacific from
the tropics, leading to anomalous cyclonic circulation and low pressure over the
WTP region. The warm SST anomaly further develops due to the SST-sea level
pressure-cloud-longwave radiation positive feedback. Our findings suggest that
the Atlantic Ocean acts as a key pacemaker for the western Pacific decadal
climate variability.
PMID- 28685762
TI - Opportunities and challenges in phenotypic drug discovery: an industry
perspective.
AB - Phenotypic drug discovery (PDD) approaches do not rely on knowledge of the
identity of a specific drug target or a hypothesis about its role in disease, in
contrast to the target-based strategies that have been widely used in the
pharmaceutical industry in the past three decades. However, in recent years,
there has been a resurgence in interest in PDD approaches based on their
potential to address the incompletely understood complexity of diseases and their
promise of delivering first-in-class drugs, as well as major advances in the
tools for cell-based phenotypic screening. Nevertheless, PDD approaches also have
considerable challenges, such as hit validation and target deconvolution. This
article focuses on the lessons learned by researchers engaged in PDD in the
pharmaceutical industry and considers the impact of 'omics' knowledge in defining
a cellular disease phenotype in the era of precision medicine, introducing the
concept of a chain of translatability. We particularly aim to identify features
and areas in which PDD can best deliver value to drug discovery portfolios and
can contribute to the identification and the development of novel medicines, and
to illustrate the challenges and uncertainties that are associated with PDD in
order to help set realistic expectations with regard to its benefits and costs.
PMID- 28685766
TI - Gut microbiota: Link between the gut and adipose tissues.
PMID- 28685761
TI - Remyelination therapies: a new direction and challenge in multiple sclerosis.
AB - Multiple sclerosis is characterized by inflammatory activity that results in
destruction of the myelin sheaths that enwrap axons. The currently available
medications for multiple sclerosis are predominantly immune-modulating and do not
directly promote repair. White matter regeneration, or remyelination, is a new
and exciting potential approach to treating multiple sclerosis, as remyelination
repairs the damaged regions of the central nervous system. A wealth of new
strategies in animal models that promote remyelination, including the
repopulation of oligodendrocytes that produce myelin, has led to several clinical
trials to test new reparative therapies. In this Review, we highlight the biology
of, and obstacles to, remyelination. We address new strategies to improve
remyelination in preclinical models, highlight the therapies that are currently
undergoing clinical trials and discuss the challenges of objectively measuring
remyelination in trials of repair in multiple sclerosis.
PMID- 28685768
TI - Obesity: Gut microbiome and serum metabolome changes.
PMID- 28685767
TI - Type 1 diabetes mellitus is a heterogeneous disease.
PMID- 28685769
TI - beta-Cell mass versus function in type 1 diabetes mellitus: truth or dare?
PMID- 28685771
TI - It takes two to transport via an elevator.
AB - Membrane transporter proteins are critical for cellular uptake and export of
molecules, and are reported to function by a number of different molecular
mechanisms. The new occluded state structure of the uracil transporter, UraA,
from Escherichia coli, reveals that both coordinated movement of the two domains
of a single protomer together with dimer formation are important for transport
activity.
PMID- 28685772
TI - Genetic enhancement in cultured human adult stem cells conferred by a single
nucleotide recoding.
PMID- 28685770
TI - Existing drugs as broad-spectrum and potent inhibitors for Zika virus by
targeting NS2B-NS3 interaction.
AB - Recent outbreaks of Zika virus (ZIKV) highlight an urgent need for therapeutics.
The protease complex NS2B-NS3 plays essential roles during flaviviral polyprotein
processing, and thus represents an attractive drug target. Here, we developed a
split luciferase complementation-based high-throughput screening assay to
identify orthosteric inhibitors that directly target flavivirus NS2B-NS3
interactions. By screening a total of 2 816 approved and investigational drugs,
we identified three potent candidates, temoporfin, niclosamide, and nitazoxanide,
as flavivirus NS2B-NS3 interaction inhibitors with nanomolar potencies.
Significantly, the most potent compound, temoporfin, not only inhibited ZIKV
replication in human placental and neural progenitor cells, but also prevented
ZIKV-induced viremia and mortality in mouse models. Structural docking suggests
that temoporfin potentially binds NS3 pockets that hold critical NS2B residues,
thus inhibiting flaviviral polyprotein processing in a non-competitive manner. As
these drugs have already been approved for clinical use in other indications
either in the USA or other countries, they represent promising and easily
developed therapies for the management of infections by ZIKV and other
flaviviruses.
PMID- 28685775
TI - Association between diet quality measured by the Healthy Food Intake Index and
later risk of gestational diabetes-a secondary analysis of the RADIEL trial.
AB - This corrects the article DOI: 10.1038/ejcn.2016.275.
PMID- 28685773
TI - Inhibition of the B7-H3 immune checkpoint limits tumor growth by enhancing
cytotoxic lymphocyte function.
AB - The interaction between tumor and the immune system is still poorly understood.
Significant clinical responses have been achieved in cancer patients treated with
antibodies against the CTLA4 and PD-1/PD-L1 checkpoints; however, only a small
portion of patients responded to the therapies, indicating a need to explore
additional co-inhibitory molecules for cancer treatment. B7-H3, a member of the
B7 superfamily, was previously shown by us to inhibit T-cell activation and
autoimmunity. In this study, we have analyzed the function of B7-H3 in tumor
immunity. Expression of B7-H3 was found in multiple tumor lines, tumor
infiltrating dendritic cells, and macrophages. B7-H3-deficient mice or mice
treated with an antagonistic antibody to B7-H3 showed reduced growth of multiple
tumors, which depended on NK and CD8+ T cells. With a putative receptor expressed
by cytotoxic lymphocytes, B7-H3 inhibited their activation, and its deficiency
resulted in increased cytotoxic lymphocyte function in tumor-bearing mice.
Combining blockades of B7-H3 and PD-1 resulted in further enhanced therapeutic
control of late-stage tumors. Taken together, our results indicate that the B7-H3
checkpoint may serve as a novel target for immunotherapy against cancer.
PMID- 28685774
TI - Immobility responses are induced by photoactivation of single glomerular species
responsive to fox odour TMT.
AB - Fox odour 2,4,5-trimethyl thiazoline (TMT) is known to activate multiple
glomeruli in the mouse olfactory bulb (OB) and elicits strong fear responses. In
this study, we screened TMT-reactive odourant receptors and identified Olfr1019
with high ligand reactivity and selectivity, whose glomeruli are located in the
posterodorsal OB. In the channelrhodopsin knock-in mice for Olfr1019, TMT
responsive olfactory-cortical regions were activated by photostimulation, leading
to the induction of immobility, but not aversive behaviour. Distribution of
photoactivation signals was overlapped with that of TMT-induced signals, but
restricted to the narrower regions. In the knockout mice, immobility responses
were reduced, but not entirely abolished likely due to the compensatory function
of other TMT-responsive glomeruli. Our results demonstrate that the activation of
a single glomerular species in the posterodorsal OB is sufficient to elicit
immobility responses and that TMT-induced fear may be separated into at least two
different components of immobility and aversion.
PMID- 28685776
TI - On-chip inter-modal Brillouin scattering.
AB - Brillouin nonlinearities-which result from coupling between photons and acoustic
phonons-are exceedingly weak in conventional nanophotonic silicon waveguides.
Only recently have Brillouin interactions been transformed into the strongest and
most tailorable nonlinear interactions in silicon using a new class of
optomechanical waveguides that control both light and sound. In this paper, we
use a multi-mode optomechanical waveguide to create stimulated Brillouin
scattering between light-fields guided in distinct spatial modes of an integrated
waveguide for the first time. This interaction, termed stimulated inter-modal
Brillouin scattering, decouples Stokes and anti-Stokes processes to enable single
sideband amplification and dynamics that permit near-unity power conversion.
Using integrated mode multiplexers to address separate optical modes, we show
that circulators and narrowband filters are not necessary to separate pump and
signal waves. We also demonstrate net optical amplification and Brillouin energy
transfer as the basis for flexible on-chip light sources, amplifiers,
nonreciprocal devices and signal-processing technologies.
PMID- 28685777
TI - Thermodynamic stability of ligand-protected metal nanoclusters.
AB - Despite the great advances in synthesis and structural determination of
atomically precise, thiolate-protected metal nanoclusters, our understanding of
the driving forces for their colloidal stabilization is very limited. Currently
there is a lack of models able to describe the thermodynamic stability of these
'magic-number' colloidal nanoclusters as a function of their atomic-level
structural characteristics. Herein, we introduce the thermodynamic stability
theory, derived from first principles, which is able to address stability of
thiolate-protected metal nanoclusters as a function of the number of metal core
atoms and thiolates on the nanocluster shell. Surprisingly, we reveal a fine
energy balance between the core cohesive energy and the shell-to-core binding
energy that appears to drive nanocluster stabilization. Our theory applies to
both charged and neutral systems and captures a large number of experimental
observations. Importantly, it opens new avenues for accelerating the discovery of
stable, atomically precise, colloidal metal nanoclusters.
PMID- 28685778
TI - Fifth annual workshop of cytoreductive surgery for advanced ovarian cancer and
peritoneal surface malignancies.
AB - The Fifth Annual Advanced Course in Cytoreductive Surgery for Ovarian Cancer and
Peritoneal Surface Malignancies was held at and sponsored by the Division of
Gynecologic Oncology at the the University of California, Irvine on Friday and
Saturday, October 9-10, 2015. The workshop was comprised of didactic modules,
historical treatise, an impassioned tribute, a cadaver laboratory, and heated
intraperitoneal chemotherapy demonstration. This was a not-for-profit workshop,
and registration fees were used to support course faculty travel to U.C. Irvine
and to pay for the cadavers. The original 56 available spots were filled within
three weeks of the initial announcement, prompting procurement of two additional
cadavers to satisfy registration overflow and accommodate the six U.C. Irvine
fellows-in-training. While international participation in the Workshops continues
to rise, we have also noted more U.S.-trained Gynecologic Oncologists among the
registrants.
PMID- 28685779
TI - An esterase-activated click and release approach to metal-free CO-prodrugs.
AB - One major challenge in the development of CO as a therapeutic agent is its
controllable delivery in a pharmaceutically acceptable form. Herein, we describe
for the first time a general chemical strategy to esterase-sensitive organic CO
prodrugs.
PMID- 28685780
TI - Cyanotetrazolylborohydride (CTB) anion-based ionic liquids with low viscosity and
high energy capacity as ultrafast-igniting hypergolic fuels.
AB - A series of hypergolic cyanotetrazolylborohydride (CTB) anion-based ionic liquids
have been synthesized by a straightforward N-hydroboration of tetrazole followed
by a salt metathesis reaction, which exhibited remarkably low viscosity (<20 mPa
s), high density (often >1.1 g cm-3), and ultra-short ignition delay time (as
short as 1.4 ms) upon contact with white fuming nitric acid (WFNA).
PMID- 28685781
TI - Cross-coupling of aromatic esters and amides.
AB - Catalytic cross-coupling reactions of aromatic esters and amides have recently
gained considerable attention from synthetic chemists as de novo and efficient
synthetic methods to form C-C and C-heteroatom bonds. Esters and amides can be
used as diversifiable groups in metal-catalyzed cross-coupling: in a
decarbonylative manner, they can be utilized as leaving groups, whereas in a non
decarbonylative manner, they can form ketone derivatives. In this review, recent
advances of this research topic are discussed.
PMID- 28685782
TI - Magnetically manipulated droplet splitting on a 3D-printed device to carry out a
complexometric assay.
AB - A method for performing droplet actuation, splitting, and dispensing using only
magnetic force and physical confinement is reported. The combination of low
friction superhydrophobic surfaces and droplets containing superparamagnetic
particles is demonstrated to reliably dispense droplets with a precision (<=6%)
similar to standard air-displacement pipettes. The 3D printed microfluidic chips
incorporate individual wells, a weir structure and differential channel depths to
facilitate droplet splitting in differing ratios. Both empirical observations and
numerical simulations show that the splitting is a combination of wetting and
pressure differences. The method enables a parent drop to be dispensed and split
into droplets ranging in size from 5-20 MUL using different well volumes. Once
dispensed/split the droplets can be further actuated, merged and mixed. An EDTA
based complexometric colorimetric titration for water hardness is conducted on
chip. The degree of colour change is then determined utilizing a cell phone
camera and image analysis and used to calculate water hardness; this measurement
was found to agree with the traditional, larger scale method. The simple, robust
dispensing method is adaptable to other digital microfluidic assays.
PMID- 28685783
TI - A silver(i)-induced higher-ordered structure based on planar chiral
tetrasubstituted [2.2]paracyclophane.
AB - Optically active phenylene-ethynylene dimers with pyridine groups based on a
planar chiral 4,7,12,15-tetrasubstituted [2.2]paracyclophane were synthesized.
The chiral conformation was controlled by pyridine-Ag(i) coordinations. After
Ag(i) coordination, the resulting higher-ordered structure dramatically enhanced
the signal intensity of circular dichroism (CD) and decreased that of circularly
polarized luminescence (CPL).
PMID- 28685784
TI - beta-Pyridylenolate zinc catalysts for the ring-opening homo- and
copolymerization of epsilon-caprolactone and lactides.
AB - A family of zinc beta-pyridylenolates with varying alpha,beta-substituents has
been synthesized. A direct reaction of beta-pyridyl ketone ligands with ZnEt2 in
toluene afforded dimeric [LZnEt]2 (L = (2-C5H4N)-C(R1)[double bond, length as m
dash]C(R2)-O-). X-ray structural data revealed that all the [LZnEt]2 complexes
exist as MU-O-bridged dimers in the solid state, although they adopt a different
geometry. Each of the [LZnEt]2 complexes is a highly active catalyst for the ring
opening polymerization (ROP) of epsilon-caprolactone (epsilon-CL) and racemic
lactide (rac-LA), respectively. The donating group on the enolate ligand can
accelerate the ROP reaction and control the polymerization process well. All
complexes also showed different abilities in the block and random
copolymerization of epsilon-CL and l-LA. Diblock PCL-b-PLLA and PLLA-b-PCL
copolymers were easily prepared via sequential addition of epsilon-CL and l-LA by
using complex 10, respectively. Random copolymers of PCL-ran-PLLA were also
synthesized from complex 10. The copolymers of PCL-ran-PLLA were shown to possess
monomer contents which matched well with their composition in the monomer feed.
NMR and DSC characterization confirmed a highly random structure of these
copolymers, resulting in closely average lengths of the caproyl and lactidyl
sequences (LCL = 2.1; LLA = 1.9). All zinc complexes as efficient single
component initiators in both homo- and copolymerizations showed that polymers
were probably susceptible to chain transfer and transesterification due to the
close ZnZn proximity in the dimer. The polymers initiated by [LZnEt]2 in the
absence of BnOH showed high molecular weight and narrow molecular weight
distributions.
PMID- 28685785
TI - Identification of human flap endonuclease 1 (FEN1) inhibitors using a machine
learning based consensus virtual screening.
AB - Human Flap endonuclease1 (FEN1) is an enzyme that is indispensable for DNA
replication and repair processes and inhibition of its Flap cleavage activity
results in increased cellular sensitivity to DNA damaging agents (cisplatin,
temozolomide, MMS, etc.), with the potential to improve cancer prognosis. Reports
of the high expression levels of FEN1 in several cancer cells support the idea
that FEN1 inhibitors may target cancer cells with minimum side effects to normal
cells. In this study, we used large publicly available, high-throughput screening
data of small molecule compounds targeted against FEN1. Two machine learning
algorithms, Support Vector Machine (SVM) and Random Forest (RF), were utilized to
generate four classification models from huge PubChem bioassay data containing
probable FEN1 inhibitors and non-inhibitors. We also investigated the influence
of randomly selected Zinc-database compounds as negative data on the outcome of
classification modelling. The results show that the SVM model with inactive
compounds was superior to RF with Matthews's correlation coefficient (MCC) of
0.67 for the test set. A Maybridge database containing approximately 53 000
compounds was screened and top ranking 5 compounds were selected for enzyme and
cell-based in vitro screening. The compound JFD00950 was identified as a novel
FEN1 inhibitor with in vitro inhibition of flap cleavage activity as well as
cytotoxic activity against a colon cancer cell line, DLD-1.
PMID- 28685786
TI - On-chip cell sorting by high-speed local-flow control using dual membrane pumps.
AB - Although researchers have proposed various methods of on-chip cell sorting, high
throughput sorting of large cells remains hampered by the difficulty of
controlling high-speed flow over a wide sorting area. To overcome this problem,
we proposed high-speed local-flow control using dual membrane pumps driven by
piezoelectric actuators placed on the outside of a microfluidic chip in this
paper. We evaluated the controllability of shifting the flow profile by the local
flow. The results indicated that we could sort large cells up to approximately
150 MUm in size with an equivalent throughput of 31 kHz. Because our method can
control the flow profiles, it is applicable not only to large cells but also to
small cells. The cell-sorting efficacy of the proposed method was experimentally
evaluated on Euglena gracilis NIES-48 (E. gracilis) cells as large target cells
and GCIY-EGFP (GCIY) cells derived from a gastric cancer cell line as small
target cells. In E. gracilis cells sorting, the throughput is 23 kHz with a 92.8%
success rate, 95.8% purity, and 90.8% cell viability. In GCIY sorting, the
throughput is 11 kHz with a 97.8% success rate, 98.9% purity, and 90.7% cell
viability. These results confirm that the proposed method sorts differently sized
cells with high throughput and hence, overcomes the throughput-size trade-off
that exists in conventional on-chip cell sorters.
PMID- 28685787
TI - Unveiling a VEGF-mimetic peptide sequence in the IQGAP1 protein.
AB - The ability to modulate angiogenesis by chemical tools has several important
applications in different scientific fields. With the perspective of finding
novel proangiogenic molecules, we searched peptide sequences with a chemical
profile similar to that of the QK peptide, a well described VEGF mimetic peptide.
We found that residues 1617-1627 of the IQGAP1 protein show molecular features
similar to those of the QK peptide sequence. The IQGAP1-derived synthetic peptide
was analyzed by NMR spectroscopy and its biological activity was characterized in
endothelial cells. These studies showed that this IQGAP1-derived peptide has a
biological activity similar to that of VEGF and could be considered as a novel
tool for reparative angiogenesis.
PMID- 28685789
TI - Orchestration of dynamic copper navigation - new and missing pieces.
AB - A general principle in all cells in the body is that an essential metal - here
copper - is taken up at the plasma membrane, directed through cellular
compartments for use in specific enzymes and pathways, stored in specific
scavenging molecules if in surplus, and finally expelled from the cells. Here we
attempt to provide a critical view on key concepts involved in copper transfer
across membranes and through compartments in the human body. The focus of this
review is on the influence of bioinorganic and thermodynamic rules on the flow in
cellular copper networks. Transition of copper from one oxidation state to
another will often lead to errant electrons that are highly reactive and prone to
form radicals and reactive oxygen or nitrogen species (ROS and RNS). Strict
control of potentially toxic oxidative species is an important part of
understanding the edge of human copper metabolism. The present review critically
covers translocation across simple and complex membranes as well as extracellular
and intracellular copper routing. We discuss in depth four tissues with polarized
cell barriers - the gut, liver, kidneys, and brain - to illustrate the
similarities and differences in transcellular transfer. Copper chaperoning,
buffering and binding dynamics to guide the metal to different sites are also
covered, while individual molecular interaction kinetics are not detailed.
Sorting and targeting mechanisms and principles crucial for correct localisation
will also be touched upon.
PMID- 28685788
TI - C-Peptide replacement therapy in type 1 diabetes: are we in the trough of
disillusionment?
AB - Type 1 diabetes is associated with such complications as blindness, kidney
failure, and nerve damage. Replacing C-peptide, a hormone normally co-secreted
with insulin, has been shown to reduce diabetes-related complications.
Interestingly, after nearly 30 years of positive research results, C-peptide is
still not being co-administered with insulin to diabetic patients. The following
review discusses the potential of C-peptide as an auxilliary replacement therapy
and why it's not currently being used as a therapeutic.
PMID- 28685790
TI - Synthesis of fluorescent heterocycles via a Knoevenagel/[4 + 1]-cycloaddition
cascade using acetyl cyanide.
AB - A concise one-pot three-component reaction that affords fluorescent indolizines,
benzo[d]pyrrolo[2,1-b]thiazoles, and pyrrolo[1,2-a]pyrazines is reported. The
methodology involves the formation of a heterocyclic 1-aza-1,3-diene derived from
a Knoevenagel condensation between an aldehyde and 2-methyl-ene-cyano aza
heterocycles, followed by [4 + 1] cycloaddition of acetyl cyanide behaving as a
non-classical isocyanide replacement.
PMID- 28685791
TI - Aggregation dynamics of nanoparticles at solid-liquid interfaces.
AB - The dynamics of molecules or nanoparticles (NPs) at solid-liquid interfaces plays
an important role in many natural and industrial processes. However, the effects
of a solid-liquid interface on NP motion and on the interactions between these
NPs is still not well understood. Here, using in situ liquid cell transmission
electron microscopy (TEM), we directly observed the movement of gold NPs and
their aggregation dynamics at solid-liquid interfaces. We found that the solid
surfaces transiently pin the NPs during their aggregation, dampening their
translational and rotational movements. This surface pinning reduces both the
movement of NPs and their aggregation rate as the aggregates grow by attachment.
However, the pinning of the NP aggregates affects their translational and
rotational motions differently. Initially, with increasing aggregate size, the
aggregate's translational motion dampens more than its rotational motion.
Consequently, the initial aggregation stages are driven by both the translational
and rotational motions, whereas the rotational motion dominates the later
aggregation stages. Our results provide insight into the movements of NPs and
their aggregates at solid-liquid interfaces, which may assist in the future
design and control of NP assemblies at interfaces.
PMID- 28685792
TI - Digestive neuroendocrine tumors: reclassifying of 26 cases according to 2010 who
classification.
AB - BACKGROUND: The classification of digestive neuroendocrine tumors is difficult
due to their heterogeneity and rareness. AIMS: Reclassify the digestive
neuroendocrine tumors according to the WHO-2010 classification . Methods: A
retrospective study included 26 patients having digestive neuroendocrine
tumors , is achieved in our Pathology Laboratory of the Military Hospital of
Tunis between 2000 and 2013. RESULTS: The mean age of patients was 49.64 years.
The Sex ratio was 1.36. It was 6 gastric tumors, 5 small intestine tumors , 5
pancreatic tumors, 5 appendix tumors , one hypatic tumor, one gall bladder
tumor , one rectal tumor and one colon tumor. According to the WHO -2000
classification, tumors are categorised into 11 well differentiated endocrine
tumors, 13 well differentiated endocrine carcinoma and 2 poorly differentiated
carcinoma . According to the WHO -2010 classification, tumors were re-evaluated
as 16 neuroendocrine tumors grade 1, 6 neuroendocrine tumors grade 2 and 4
neuroendocrine carcinoma . CONCLUSION: There was a concordance between the two
classifications in 93% of cases. The WHO -2010 classification may allow a better
classification for the digestive neuroendocrine tumors, however there are some
histological categories that remained difficult to classify.
PMID- 28685793
TI - Comparative study of two complementary proliferation markers in 200 breast
carcinomas: Ki67 and mitotic index.
AB - BACKGROUND: The evaluation of the proliferation in the mammary carcinomas
provides useful prognostic and predictive information for subsequent management.
The purely morphological evaluation of proliferative activity was represented by
the evaluation of mitotic index. New analytical methods were gradually developed
and performed. Among these methods, evaluation of Ki67 by immunohistochemistry is
particularly interesting. Its expression is significantly increased in the cell
cycle. AIM: To correlate the mitotic index as a classic method of assessing cell
proliferation and Ki 67 proliferation index detected by immunohistochemistry to
identify the most reliable proliferative marker. METHODS: We studied 200 patients
with invasive ductal carcinoma breast over a period of 12 months of 2014. We
identified in each case the SBR grade, Ki67 proliferation index and the mitotic
index. Correlation between the two parameters was identified using the Spearman
test. A result is considered significant when p < 0.01. The distribution of these
markers by SBR gradewas studied using the ANOVA method. RESULTS: Ki67 is
significantly correlated to the mitotic index. Although these two methods are
dependent, Ki67 is the most sensitive and bonded to SBR grade. Determination of
Ki67 provides interesting information that could replace the mitotic account. It
provides reliable and reproducible data that can be incorporated into a
prognostic score. CONCLUSION: Ki67 is a more efficient marker mitotic index,
reflecting the cell proliferation.
PMID- 28685794
TI - Rectal adenocarcinoma: 154 cases prognosis study.
AB - BACKGROUND: during this century, therapeutic management of rectal cancer has
known a lot of advances. Survival is still depending on factors related to the
patient, the tumor or the surgeon. AIM: The aim of our study is to report
survival and prognosis factors of our patients managed for a rectal cancer.
METHODS: We report an descreptive retrospective study about 154 patients. SPSS
19.0 version was used for the statistical analysis. Desriptive study was done
using means, and pourcentage. Survival was analysed using Kaplan meier curve. In
univariate analysis, we calculated the odd ratio in order to evaluate risk
factors. Multivariate analysis used Cox model. Significancy was 0.05. RESULTS:
Global survival was 52.4% at 3 years and 42.4% at 5 years. Free reccurence
survival was 76% at 3 years and 69.15% at 5 years. In univariate analysis,
factors significantly influencing survival were age>70 years, CAE level, tumor
perforation, TNM, tumor differentiation, peroperative blood transfusion, and
reccurency. In multivriate analysis, only age > 70 years, T and local reccurency
were independants factors influencing survival. CONCLUSION: A better knowledge
of prognosis factors ead to a better management of this cancer with more adjuvant
treatment indications and closer monitoring.
PMID- 28685795
TI - The risk of acute coronary syndrome in Ramadan.
AB - BACKGROUND: Data on the effect of fasting on coronary disease are rare and
controversial. The aim of our study was to investigate the influence of Ramadan
on the prevalence of acute coronary syndrome among chest pain patients in the
emergency department of Monastir. METHODS: It was a prospective study, performed
in the emergency department of Fattouma Bourguiba University Hospital of
Monastir, during the 3 months before, during and after Ramadan from 2012 to 2014.
We included all patients with non-traumatic chest pain during the study period.
Data were collected using a standardized form. The uniformity chi 2 test, ANOVA
test, Kruskal-Wallis test were performed at the 5% level. Binary logistic
regression model was used for multivariate analysis. RESULTS: The SCA prevalence
was 17% a month before Ramadan, 22% during Ramadan and 28% one month after
Ramadan (p = 0.007). According to the results of the multivariate analysis, the
period of Ramadan is not associated with increase of risk of SCA whereas the risk
doubles after Ramadan in all group (p = 0.001). In subgroups analysis, the period
of R was associated with an amplification of risk in men aged more than 55 years
and women older than 65 years (OR: 2.1; p = 0.020) and among subjects with
hypertension (OR: 2.4, p = 0.007). Ramadan and Shawwal were not associated with
an increase of risk among subjects without CVX risk factor. CONCLUSION: We have
demonstrated that the risk of SCA has increased in Ramadan only among the elderly
and patient with hypertension. The increased risk in Shawwal can be explained by
the lifting of dietary restriction.
PMID- 28685796
TI - Tuberculosis cost in tunisia.
AB - BACKGROUND: Tuberculosis (TB) infects one third of the world population. Its
economic impact is important, affecting the global economy in the World.
OBJECTIVE: To determine the economic costs related to tuberculosis in Tunisia.
METHODS: Calculations were made for the reference year 2013; we covered all cost
components of the disease, which are related to program management, BCG
vaccination, health workers training, social mobilization, screening,
chemoprophylaxis, and tuberculosis care. With the exception of costs related to
care, which were the subject of a specific survey, the costs of other categories
were obtained from the National TB Control Program. RESULTS: The cost of the
different components related to the management, prevention, screening and
tuberculosis care in 2013 amounted 504688,000DT. The cost of care represented
80.0% of total costs (6807 808,000DT) ; cost related to program management
represented 13.2% (1 121 580,00 DT) and the BCG vaccination 6.0% e (512
300,00DT) The average cost per patient was 1447,360 DTin 2013. CONCLUSION:
Reducing the cost of tuberculosis, would involve reducing diagnostic delay. It is
also recommended to reduce hospitalization recourse, and prevent multidrug
resistance which lead to additional expenditures.
PMID- 28685797
TI - Impact of obstructive sleep apnea on the right ventricle.
AB - BACKGROUND: Right ventricular (RV) involvement in obstructive sleep apnea
syndrome (OAS) is controversial. The aim of this study was to determine a
correlation between echocardiographic parameters of RV function and severity of
OSA assessed by the apnea- hypopnea index (AHI). METHODS: Sixty patients with
suspected OSA were enrolled. All patients had overnight polygraphy and an
echocardiographic assessment of RV structure and function. Patients were divided
into three groups: a control group (n=20) with an AHI<5/h, a group of mild to
moderate OSA (n=18) with an AHI=5-30/h and a group of severe OSA (n=22) with
AHI>=30/h. RESULTS: There were no differences of age, body mass index and sex
among the three groups. There was no difference in systolic pulmonary pressure.
RV free wall thickness, end-diastolic surface and right atrium surface were
statistically higher in OSA patients compared with controls. The peak systolic
myocardial velocity at tricuspid lateral annulus S' were significantly lower in
patients compared with controls (14.5+/-3 vs 12.2+/-2 cm / s, p<0.001;
respectively). This decrease was greater in patients with severe OSA compared
with mild to moderate OSA (11.4+/-3 vs 13.0+/-1 cm/s, p=0.05, respectively).
Right ventricular myocardial performance index (MPI) was significantly higher in
OSA compared with controls (0.55+/-0.12 vs 0.46+/-0.14, p=0.024, respectively)
but it was not correlated with the severity of IAH. CONCLUSIONS: In OSA patients,
there was a significant RV dysfunction independently of pulmonary pressure,
although the correlation with the severity of IAH was moderate.
PMID- 28685798
TI - Cyto-colpo-histologic correlation: about an analytical study of 120 colposcopies.
AB - PROBLEM: Cervical cancer is the second gynecological cancer Tunisian women after
breast. This is a sexually transmitted disease including the role of HPV has been
proven. Cervical cancer screening is possible due to the accessibility of the
cervix with a speculum examination and implementation of cervical smear. AIM OF
THE WORK: To study the epidemiological and clinical data of patients, analyze the
results of the Pap test, colposcopy and cervical biopsy staging are the lesions
observed in colposcopy, compare the results of smears, colposcopy and cervical
biopsy. METHODS: A retrospective analytical study about 120 observations of
patients who underwent colposcopy and biopsy of the cervix over a seven year
period from January 2006 to December 2012. RESULTS: The mean age of patients was
46.6 years. The mean gravidity was 4.99. The mean parity was 4.07. The average
age of first sexual intercourse was 24 years. 95.83% of the patients were
married. Four patients had multiple partners, 3, 33%. Eighty-one patients 67.5%
were genital activity. Two patients had a history of pelvic infection is 1.66%. A
history of repeated low genital infection were found in 20 patients, or 16.66%.
HPV testing was requested for two patients. The genotypes found were 16, 35 and
53. The most common reasons were essentially pathological smears, pelvic pain and
exploration of bleeding. The FCU was performed in 98 patients either in 81.66% of
cases. The smear was pathological in 83 patients or 84.69% of smears. He showed:
a persistent inflammatory smears in 64 women, or 65.30% of the cases, 6 ASCUS or
6.12% of cases, 13 cervical dysplasia or 13.26% of cases: 8 CIN1 or 8.16% of
event; 1 CIN2 or 1.02% and 4 CIN 3, or 4.08% of cases. Colposcopy was indicated
before an abnormal smear: In 83 patients either in 69.16% of cases. Colposcopy
was performed in front of an abnormal appearance of the cervix in 37 patients.
Colposcopy has concluded that: normal cervix in 28 patients or 23.33% of the
cases, cervicitis appearance in 15 patients or 12.5% of cases, ectropion in 23
patients or 19.2% of cases, with TAGI 47 patients or 39.2% of cases, a TAG2 in 6
patients either 5% of cases, ulceration in a patient or 0.83% of cases. Cervical
biopsy objectified normal mucosa in 19 patients, or 15.8% of cases. She
objectified cervical metaplasia in 11 patients, or 9.2% of cases, ectropion in a
patient, or 0.8% of cases, cervicitis in 56 patients, or 46.7% of cases,
condyloma in 2 patients, 1.7% of cases, CIN 1 in 6 patients, 5% of cases, CIN2 in
4 patients, soit3,3% of CIN3 and in 3 patients, 2.5% of cases. FCU had a
sensitivity of 60%, a specificity of 95.18%, positive predictive value of 69% and
a negative predictive value of 93%. The sensitivity of colposcopy was 66% and
specificity of59%. Positive predictive value of 18% and a negative predictive
value of 92%. For high-grade dysplasia, colposcopy had a sensitivity of 85%,
specificity 58%, positive predictive value of 11.3% and a negative predictive
value of 98%. Cervical biopsy finds carcinoma in situ in two cases and squamous
micro-invasive carcinoma in one case. The treatments were performed essentially a
cervical electrocoagulation in 8 patients, a cone biopsy in 7 patients and post
conization hysterectomy in 2 patients. CONCLUSION: Colposcopy is a harmless and
reliable examination to guide the cervical biopsy. Tracks smear, colposcopy and
directed biopsy confirmed.
PMID- 28685799
TI - Zenker's diverticulum.
PMID- 28685800
TI - Intraosseous hibernoma: a case report and review of the literature.
AB - : Intraosseous hibernoma is a rare benign bone tumor, with only 4 cases reported
in English literature. CASE REPORT: In this report, we describe a 42-year-old man
with no past medical history and right chest pain. Imaging studies showed an
osteolytic lesion with fat attenuation lesion in the right fourth rib. The lesion
was completely resected and microscopic study showed mildly thickened bone
trabeculae and multivacuolated brown fat cells replacing the normal white fat and
hematopoietic elements. The diagnostic of intraosseous hibernoma was made.
CONCLUSION: Although it is rare, hibernoma should be included in the differential
diagnosis of lipomatous tumors.
PMID- 28685801
TI - Can CS gas induce myocardial infarction?
AB - "2-chlorobenzylidene malononitrile" also named CS gas is the most used riot
control agent in the world. Its reputation as the least toxic tear gas explains
its large use by different authorities. Early exposure to CS spray commonly
induces visual irritation, skin reactions, with increased mucous secretion in
order to temporarily incapacitate targeted people. However, there is a large
agreement that safety data of this product is limited and further studies need to
be performed since serious problems could occur after heavy exposure such as loss
of consciousness, laryngospasm, pulmonary edema and hemorrhage... Herein, we
report a case of a young man who had acute myocardial infarction with serious
cardiac sequelae after exposure to tear gas. To our knowledge, this is the second
case since forty years in the literature that directly links documented acute
heart infarction to CS gas exposure.
PMID- 28685802
TI - Hemorrhagic Meckel's diverticulum. Interest of the digestive pertechnetate
scintigraphy.
AB - Meckel's diverticulum is the most prevalent congenital abnormality of the
gastrointestinal tract. Clinical symptoms can result in pain, bleeding and
perforation caused by peptic ulceration. Among all imaging modalities, Tc-99m
pertechnetate scintigraphy is the most sensitive method for Meckel's diverticulum
diagnosis, but only mentioned in a few publications. We report the case of a
young child with rectal bleeding related hemorrhagic Meckel's diverticulum.
Endoscopy and ultrasound were normal. The diagnosis was done by scintigraphy with
technetium revealing an accumulation of radiotracer by mucous cells in ectopic
gastric mucosa, which allows a detection of Meckel's diverticulum. Our case
illustrates the importance of this exam to the diagnosis of gastrointestinal
bleeding with normal endoscopy.
PMID- 28685803
TI - Familial juvenile colloid milium.
PMID- 28685804
TI - Parathyromatosis: a rare cause of persistent primary hyperparathyroidism.
PMID- 28685805
TI - An exceptional cause of upper gastrointestinal hemorrhage: Thoracic aorta
aneurysm.
PMID- 28685806
TI - Lung herniation: a case report of a spontaneous cervical hernia.
PMID- 28685807
TI - SRY- negative 46, XX male with complete virilization and infertility: A case
report.
PMID- 28685808
TI - Renal function replacement by hemodialysis: forty-year anniversary and a glimpse
into the future at hand.
AB - From its introduction in 1943 and until the late 1970s, hemodialysis (HD) has
been a lengthy and cumbersome treatment administered by a few skilled physicians
and technicians to a very limited number of terminal kidney patients. The
technological innovations introduced over the years made HD a treatment
administered and supervised by nursing personnel to a very large numbers of
kidney patients, hopefully until recovery of kidney functions or kidney
transplantation. In 2013, it is estimated that 2.250.00 kidney patients were
treated worldwide, and their number is steadily increasing. Shortage of
transplant kidneys and quality of current treatments has contributed to
increasing the survival of HD patients. Today, it is not unusual to find patients
who have been on HD for longer than twenty years. All this generated the feeling
that performance of membranes and dialysis technology has reached its limit.
Recently, the increasing economic burden of healthcare caused by people ageing
and the increasing incidence of degenerative diseases (e.g. diabetes and
cardiovascular diseases), and the economic crisis has pushed many governments and
health insurances to cut resources for healthcare. The main consequence is that
investments in research and development in HD have been significantly reduced.
The question is whether there is indeed no need for innovation in HD.In this
paper, it is discussed how the paradigm of HD has changed and what possibly are
now the drivers for innovation in HD. A few ideas are proposed that could be
developed by adapting existing technologies to the future needs of HD.
PMID- 28685809
TI - Follow-up after intensive care treatment: a questionnaire survey of intensive
care aftercare in Denmark.
AB - BACKGROUND: Rehabilitation efforts after treatment in the intensive care unit
(ICU) are termed intensive care aftercare. It includes both early in-hospital
follow-up after ICU-discharge and late follow-up after hospital discharge. This
study aims to investigate the current ICU-aftercare activities in Denmark.
METHODS: We conducted an electronic questionnaire survey, which was distributed
by e-mail to the heads of all 31 general ICUs in Denmark. Specialized ICUs were
not included. The questionnaire was divided into the following sections: early
ICU-aftercare, late ICU-aftercare, future development and demographics. RESULTS:
Thirty-one ICUs were invited to participate. The response rate was 100%. Overall,
26 of 31 ICUs (84%) offered ICU-aftercare, with the following distribution: early
ICU-aftercare (58%), late ICU-aftercare (57%) and both (29%). There were no
significant associations between hospital size and provision of ICU-aftercare.
For early ICU-aftercare, the most common eligibility criteria were based on ICU
length of stay (LOS) (44%) and a decision based upon doctors' discretion (22%).
Incidence of guidelines for early ICU-aftercare (44%) and checklists at patient
contact (35%) were sparse. The most common early ICU-aftercare items were as
follows: respiratory care (82%), tracheostomy care (59%) and nutritional care
(59%). For late ICU-aftercare, the most common eligibility criterion was LOS
(41%). Guidelines (71%), but not checklist at patient contact (35%), were more
common. Most frequent late ICU-aftercare interventions were review of ICU-diaries
(59%) and patient charts (53%). CONCLUSION: Eighty-four per cent of Danish ICUs
offered ICU-aftercare to their patients. There was an abundant heterogeneity of
eligibility criteria and ICU-aftercare interventions.
PMID- 28685810
TI - Predictors of Independent Aging and Survival: A 16-Year Follow-Up Report in
Octogenarian Men.
AB - OBJECTIVES: To examine the longitudinal associations between aging with preserved
functionality, i.e. independent aging and survival, and lifestyle variables,
dietary pattern and cardiovascular risk factors. DESIGN: Cohort study. SETTING:
Uppsala Longitudinal Study of Adult Men, Sweden. PARTICIPANTS: Swedish men (n =
1,104) at a mean age of 71 (range 69.4-74.1) were investigated, 369 of whom were
evaluated for independent aging 16 years later, at a mean age of 87 (range 84.8
88.9). MEASUREMENTS: A questionnaire was used to obtain information on lifestyle,
including education, living conditions, and physical activity. Adherence to a
Mediterranean-like diet was assessed according to a modified Mediterranean Diet
Score derived from 7-day food records. Cardiovascular risk factors were measured.
Independent aging at a mean age of 87 was defined as lack of diagnosed dementia,
a Mini-Mental State Examination score of 25 or greater, not institutionalized,
independence in personal activities of daily living, and ability to walk outdoors
alone. Complete survival data at age 85 were obtained from the Swedish Cause of
Death Register. RESULTS: Fifty-seven percent of the men survived to age 85, and
75% of the participants at a mean age of 87 displayed independent aging.
Independent aging was associated with never smoking (vs current) (odds ratio (OR)
= 2.20, 95% confidence interval (CI) = 1.05-4.60) and high (vs low) adherence to
a Mediterranean-like diet (OR = 2.69, 95% CI = 1.14-6.80). Normal weight or
overweight and waist circumference of 102 cm or less were also associated with
independent aging. Similar associations were observed with survival. CONCLUSION:
Lifestyle factors such as never smoking, maintaining a healthy diet, and not
being obese at age 71 were associated with survival and independent aging at age
85 and older in men.
PMID- 28685811
TI - Homozygosity for a missense variant in COMP gene associated with severe
pseudoachondroplasia.
AB - The phenotypic spectrum associated with heterozygous mutations in cartilage
oligomeric matrix protein gene (COMP) range from a mild form of multiple
epiphyseal dysplasia (MED) to pseudoachondroplasia (PSACH). However, the
phenotypic effect from biallelic COMP variants is unclear. We investigated a
large consanguineous Pakistani family with a severe form of PSACH in 2
individuals. Another 14 family members presented with a mild PSACH phenotype
similar to MED. Using exome sequencing and subsequent segregation analysis, we
identified homozygosity for a COMP missense variant [c.1423G>A; p.(D475N)] in the
2 severely affected individuals, whereas family members with the mild PSACH
phenotype were heterozygous. Our observations show for the first time that a
biallelic COMP variant may be associated with pronounced and widespread skeletal
malformations suggesting an additive effect of the 2 mutated alleles.
PMID- 28685812
TI - Simulation-based training program with deliberate practice for ultrasound-guided
jugular central venous catheter placement.
AB - BACKGROUND: Current evidence supports the utility of simulation training for
bedside procedures such as ultrasound-guided jugular central venous catheter
(CVC) insertion. However, a standardized methodology to teach procedural skills
has not been determined yet. The aim of this study was to evaluate the
effectiveness of a simulation-based training program for improving novice
technical performance during ultrasound-guided internal jugular CVC placement.
METHODS: Postgraduate year 1 (PGY-1) residents from anesthesiology, emergency
medicine, cardiology, ICU, and nephrology specialties were trained in four
deliberate practice sessions. Learning objectives included principles of
ultrasound (US), preparation (gown, glove, draping), procedural skills I (US
scanning and puncture), and procedural skills II (catheter insertion). CVC
technical proficiency was tested pre- and post-training using hand-motion
analysis with the Imperial College Surgical Assessment Device (ICSAD) and a
global rating scale (GRS). RESULTS: Thirty-five PGY-1 residents successfully
completed the program. These novices' GRS scores improved significantly after the
training (P < 0.001). Total path length measured with the ICSAD decreased
significantly after the training (P = 0.008). Procedural time decreased
significantly after training from 387 (310-501) seconds to 200 (157-261) seconds
(median and interquartile range) (P = 0.029). CONCLUSION: This simulation
training program based on deliberate practice significantly increased the
technical skills of residents in US-guided short-axis, out-of-plane internal
jugular CVC placement. Data also confirm the validity of the ICSAD as an
assessment tool for ultrasound-guided internal jugular CVC placement learning.
PMID- 28685813
TI - The evolution of phenotypic integration: How directional selection reshapes
covariation in mice.
AB - Variation is the basis for evolution, and understanding how variation can evolve
is a central question in biology. In complex phenotypes, covariation plays an
even more important role, as genetic associations between traits can bias and
alter evolutionary change. Covariation can be shaped by complex interactions
between loci, and this genetic architecture can also change during evolution. In
this article, we analyzed mouse lines experimentally selected for changes in size
to address the question of how multivariate covariation changes under directional
selection, as well as to identify the consequences of these changes to evolution.
Selected lines showed a clear restructuring of covariation in their cranium and,
instead of depleting their size variation, these lines increased their magnitude
of integration and the proportion of variation associated with the direction of
selection. This result is compatible with recent theoretical works on the
evolution of covariation that take the complexities of genetic architecture into
account. This result also contradicts the traditional view of the effects of
selection on available covariation and suggests a much more complex view of how
populations respond to selection.
PMID- 28685815
TI - Histological assessment at follicular lymphoma progression.
PMID- 28685814
TI - Drug repurposing screens and synergistic drug-combinations for infectious
diseases.
AB - : Infectious diseases account for nearly one fifth of the worldwide death toll
every year. The continuous increase of drug-resistant pathogens is a big
challenge for treatment of infectious diseases. In addition, outbreaks of
infections and new pathogens are potential threats to public health. Lack of
effective treatments for drug-resistant bacteria and recent outbreaks of Ebola
and Zika viral infections have become a global public health concern. The number
of newly approved antibiotics has decreased significantly in the last two decades
compared with previous decades. In parallel with this, is an increase in the
number of drug-resistant bacteria. For these threats and challenges to be
countered, new strategies and technology platforms are critically needed. Drug
repurposing has emerged as an alternative approach for rapid identification of
effective therapeutics to treat the infectious diseases. For treatment of severe
infections, synergistic drug combinations using approved drugs identified from
drug repurposing screens is a useful option which may overcome the problem of
weak activity of individual drugs. Collaborative efforts including government,
academic researchers and private drug industry can facilitate the translational
research to produce more effective new therapeutic agents such as narrow spectrum
antibiotics against drug-resistant bacteria for these global challenges. LINKED
ARTICLES: This article is part of a themed section on Inventing New Therapies
Without Reinventing the Wheel: The Power of Drug Repurposing. To view the other
articles in this section visit
http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.2/issuetoc.
PMID- 28685817
TI - The impact of an increased progesterone-to-follicle number ratio on live delivery
rates in women with normal ovarian reserve.
AB - OBJECTIVE: To explore the relationship between progesterone-follicle number (P/F)
ratio and live delivery rate in patients with normal ovarian reserve undergoing
cleavage-stage embryo transfer with a long gonadotropin-releasing hormone agonist
cycle. METHODS: The present retrospective study included data from patients
younger than 38 years with normal ovarian reserve who were undergoing in vitro
fertilization/intracytoplasmic sperm injection and embryo transfer at Zhongnan
Hospital, Wuhan University, China, between January 1, 2009 and December 31, 2015.
Patients underwent cleavage-stage fresh embryo transfer with a long gonadotropin
releasing hormone agonist cycle, and associations between P/F ratios and
fertility/pregnancy outcomes were analyzed. RESULTS: Patients with a P/F ratio of
0.11 or above had higher serum progesterone levels (P<0.001) and lower serum
estradiol levels (P<0.001) on the day of human chorionic gonadotropin
administration in comparison with patients with lower P/F ratios; elevated P/F
ratios were also associated with fewer follicles at least 14 mm in size (P<0.001)
and lower live delivery rates (P<0.001). Multiple logistic regression confirmed
that P/F ratio was an independent predictor of live delivery rate (P=0.001).
CONCLUSION: A P/F ratio of at least 0.11 was associated with lower live delivery
rates in women with normal ovarian reserve undergoing cleavage-stage embryo
transfer with a long gonadotropin-releasing hormone agonist cycle.
PMID- 28685816
TI - Central nervous system tumors and agricultural exposures in the prospective
cohort AGRICAN.
AB - Studies in farmers suggest a possible role of pesticides in the occurrence of
Central Nervous System (CNS) tumors but scientific evidence is still
insufficient. Using data from the French prospective agricultural cohort AGRICAN
(Agriculture & Cancer), we investigated the associations between exposure of
farmers and pesticide users to various kinds of crops and animal farming and the
incidence of CNS tumors, overall and by subtypes. Over the 2005-2007, 181,842
participants completed the enrollment questionnaire that collected a complete job
calendar with lifetime history of farming types. Associations were estimated
using proportional hazards models with age as underlying timescale. During a 5.2
years average follow-up, 273 incident cases of CNS tumors occurred, including 126
gliomas and 87 meningiomas. Analyses showed several increased risks of CNS tumors
in farmers, especially in pesticide users (hazard ratio = 1.96; 95% confidence
interval: 1.11-3.47). Associations varied with tumor subtypes and kinds of crop
and animal farming. The main increases in risk were observed for meningiomas in
pig farmers and in farmers growing sunflowers, beets and potatoes and for gliomas
in farmers growing grasslands. In most cases, more pronounced risk excesses were
observed among pesticide applicators. Even if we cannot completely rule out the
contribution of other factors, pesticide exposures could be of primary concern to
explain these findings.
PMID- 28685818
TI - Menopausal hormone therapy and risk of melanoma: Do estrogens and progestins have
a different role?
AB - The association between use of menopausal hormone therapy (HT) and occurrence of
skin malignant melanoma (SMM) is controversial. We investigated the issue in a
nationwide cohort of 684,696 Norwegian women, aged 45-79 years, followed from
2004 to 2008. The study was based on linkage between Norwegian population
registries. Multivariable Poisson regression models were used to estimate the
effect of HT use, different HT types, routes of administration and doses of
estrogen and progestin on the risk of SMM. During the median follow-up of 4.8
years, 178,307 (26%) women used HT, and 1,476 incident SMM cases were identified.
Current use of HT was associated with increased risk of SMM (rate ratios (RR) =
1.19; 95% confidence interval (CI) 1.03-1.37). Plain estrogen therapy was
associated with an increased risk of SMM (RR 1.45; 95% CI 1.21-1.73), both for
oral (RR 1.45; 95% CI 1.09-1.93) and vaginal (RR 1.44; 95% CI 1.14-1.84)
formulations, while combined estrogen and progestin therapy (EPT) was not (RR
0.91; 95% CI 0.70-1.19). We performed a dose-response analysis of estrogen and
progestin in women using tablets, and found that use of estrogens was associated
with increased risk (RR 1.24; 95% CI 1.00-1.53 per 1 mg/day) and use of
progestins with decreased risk (RR 0.71; 95% CI 0.57-0.89 per 10 mg/month) of
SMM. In conclusion, estrogens were associated with increased risk of SMM, while
combinations of estrogens and progestins were not. Our results suggest that
estrogens and progestins might affect the risk of SMM in opposite ways.
PMID- 28685819
TI - Eruptive keratoacanthomas in tattoos.
PMID- 28685820
TI - PI3K-Akt pathway enhances the differentiation of interleukin-27-induced type 1
regulatory T cells.
AB - Interleukin 27 (IL-27) has been identified as a potent cytokine in the
differentiation of type 1 regulatory T (Tr1) cells through interactions with
several key elements, including transcription factors such as aryl hydrocarbon
receptor and IL-21. Autocrine production of IL-21 is known to be important for
maintaining IL-10 expression by Tr1 cells. Although previous studies have shown
that the phosphoinositide 3-kinase (PI3K) -Akt axis contributes to the
differentiation of helper T-cell subsets, the role of the PI3K pathway on Tr1
cell differentiation remains to be elucidated. Here, we demonstrate that
suppression of the PI3K-Akt pathway results in impairment of IL-27-induced Tr1
(IL-27-Tr1) cell differentiation in vitro and in vivo. Furthermore, this
suppression down-regulates IL-21 receptor expression by Tr1 cells, followed by
suppression of IL-10 expression by IL-27-Tr1 cells. These results suggest that
the PI3K pathway enhances IL-10 expression by IL-27-Tr1 cells through up
regulation of IL-21 receptors.
PMID- 28685822
TI - Thalamic connections of the core auditory cortex and rostral supratemporal plane
in the macaque monkey.
AB - In the primate auditory cortex, information flows serially in the mediolateral
dimension from core, to belt, to parabelt. In the caudorostral dimension,
stepwise serial projections convey information through the primary, rostral, and
rostrotemporal (AI, R, and RT) core areas on the supratemporal plane, continuing
to the rostrotemporal polar area (RTp) and adjacent auditory-related areas of the
rostral superior temporal gyrus (STGr) and temporal pole. In addition to this
cascade of corticocortical connections, the auditory cortex receives parallel
thalamocortical projections from the medial geniculate nucleus (MGN). Previous
studies have examined the projections from MGN to auditory cortex, but most have
focused on the caudal core areas AI and R. In this study, we investigated the
full extent of connections between MGN and AI, R, RT, RTp, and STGr using
retrograde and anterograde anatomical tracers. Both AI and R received nearly 90%
of their thalamic inputs from the ventral subdivision of the MGN (MGv; the
primary/lemniscal auditory pathway). By contrast, RT received only ~45% from MGv,
and an equal share from the dorsal subdivision (MGd). Area RTp received ~25% of
its inputs from MGv, but received additional inputs from multisensory areas
outside the MGN (30% in RTp vs. 1-5% in core areas). The MGN input to RTp
distinguished this rostral extension of auditory cortex from the adjacent
auditory-related cortex of the STGr, which received 80% of its thalamic input
from multisensory nuclei (primarily medial pulvinar). Anterograde tracers
identified complementary descending connections by which highly processed
auditory information may modulate thalamocortical inputs.
PMID- 28685823
TI - Current Patterns of Training in Personality Assessment During Internship.
AB - OBJECTIVE: Training in broad-based objective and projective personality
assessments has been a mainstay of applied psychology. Stedman (2007) and
Piotrowski (2015) have documented a decline in projective training during
internship. This study investigated internship directors' current expectations
regarding graduate school training with objective and projective instruments,
their ratings of the importance of that training, and current training patterns
with objective and projective instruments during internship. METHOD: Participants
were 355 psychology internship programs, representing 46.1% of the Association of
Psychology Postdoctoral and Internship Centers. RESULTS: Results indicated the
following current internship training patterns: Minnesota Multiphasic Personality
Inventory (68% to 51%), Personality Assessment Inventory (59% to 25%), Millon
Clinical Multiaxial Inventory (51% to 34%), Rorschach (35 to 26%), story telling
(41% to 19%), sentence completion (41% to 18%), and drawings (36% to 9%). Adult
program directors reported higher percentages for objective tests; child program
directors reported higher percentages for projective tests. CONCLUSION: A
decreased valuation of projective techniques is now typical of current internship
training programs.
PMID- 28685821
TI - PD-1/PD-L1 inhibitors in haematological malignancies: update 2017.
AB - The introduction of PD-1/PD-L1 pathway inhibitors is an important landmark in
solid oncology with unprecedented practice-changing activity in various types of
solid tumours. Among haematological malignancies, PD-1/PD-L1 inhibitors have been
successful, so far, only in the treatment of classical Hodgkin lymphoma, which
typically exhibits an over-expression of PD-1 ligands (PD-L1, PD-L2) due to
alterations in chromosome 9p24.1. Such positive outcomes led to the US Food and
Drug Administration approval of nivolumab use in relapsed Hodgkin lymphoma in
2016 as the first haematological indication. Although the results in other
lymphoid malignancies have not been so striking, blockade of the PD-1/PD-L1 axis
has led to meaningful responses in other lymphoma types such as diffuse large B
cell lymphoma, follicular lymphoma or several T-cell lymphomas. Monotherapy with
PD-1/PD-L1 inhibitors in chronic lymphocytic leukaemia and multiple myeloma has
been unsatisfactory, suggesting that a combinational approach with other
synergistic drugs is needed. In the case of multiple myeloma, immunomodulatory
agents together with corticosteroids represent the most promising combinations.
Among myeloid malignancies, the anti-PD-1 monoclonal antibodies are examined
dominantly in acute myeloid leukaemia and myelodysplastic syndromes in
combination with potentially synergistic hypomethylating drugs such as 5
azacitidine, resulting in promising outcomes that warrant further investigation.
We have described all available clinical results of PD-1/PD-L1 inhibitors in
haematological malignancies and discussed related toxicities, as well as
highlighted crucial preclinical studies in this review.
PMID- 28685824
TI - Intraoperative music application in children and adolescents - a pilot study.
AB - BACKGROUND: Hospitalization, surgery and anaesthesia may lead to new-onset
maladaptive behaviour, emotional distress and trauma. This pilot study aims to
investigate the influence of intraoperatively applied music on post-operative
behaviour in children and adolescents. METHODS: Children with an ASA physical
state classification of I or II, aged from 4 to 16 years and scheduled for
elective circumcision or inguinal hernia repair under combined general and caudal
anaesthesia were included. The children were randomized into two groups. They
wore headphones during surgery, and were either exposed to music or not. All
involved staff were blinded. Post-operative behaviour was documented by parents
on day 7, 14 and 28 after surgery, using a questionnaire adapted from the "Post
Hospitalization Behavioural Questionnaire" (PHBQ). Overall occurrence of at least
one item indicating maladaptive behaviour was the primary outcome. Data are
presented as median (interquartile range). RESULTS: In total, 135 children aged
6.6 (5.3-8.5) years, weighing 22 (19-29) kg, were included, with 112 completed
questionnaires returned. Overall occurrence of at least one maladaptive item was
lower in the music group, with a significantly lower incidence on day 7 (51% vs.
77% in controls; P < 0.01). CONCLUSION: Intraoperative music application in
children undergoing minor surgical procedures may reduce the incidence of post
operative maladaptive behaviour within the first week.
PMID- 28685825
TI - Positive Youth Development as a Strategy for Addressing Readiness and Equity: A
Commentary.
AB - Attention to addressing child and youth disparities associated with race, gender,
and class has significantly increased the demand for guidance on how to help
local systems and organizations that already serve low-income youth and youth of
color sharpen program components and improve program practices in ways that
address the broader and often more complex needs of these populations. In this
commentary, the author reflects on how the research findings and themes in the
articles included in the special section (a) advance our ability to answer
specific questions such as how to improve social skill growth among trauma
exposed children and (b) reinforce the importance of continuing to link positive
youth development to the tenets of program quality and self-transformation.
PMID- 28685826
TI - Promoting Positive Youth Development Through School-Based Social and Emotional
Learning Interventions: A Meta-Analysis of Follow-Up Effects.
AB - This meta-analysis reviewed 82 school-based, universal social and emotional
learning (SEL) interventions involving 97,406 kindergarten to high school
students (Mage = 11.09 years; mean percent low socioeconomic status = 41.1; mean
percent students of color = 45.9). Thirty-eight interventions took place outside
the United States. Follow-up outcomes (collected 6 months to 18 years
postintervention) demonstrate SEL's enhancement of positive youth development.
Participants fared significantly better than controls in social-emotional skills,
attitudes, and indicators of well-being. Benefits were similar regardless of
students' race, socioeconomic background, or school location. Postintervention
social-emotional skill development was the strongest predictor of well-being at
follow-up. Infrequently assessed but notable outcomes (e.g., graduation and safe
sexual behaviors) illustrate SEL's improvement of critical aspects of students'
developmental trajectories.
PMID- 28685827
TI - Spatial Accessibility of Primary Care in England: A Cross-Sectional Study Using a
Floating Catchment Area Method.
AB - OBJECTIVE: To analyze the general practitioners (GPs) with regard to the degree
of urbanization, social deprivation, general health, and disability. DATA
SOURCES: Small area population data and GP practice data in England. STUDY
DESIGN: We used a floating catchment area method to measure spatial GP
accessibility with regard to the degree of urbanization, social deprivation,
general health, and disability. DATA COLLECTION: Data were collected from the
Office for National Statistics and the general practice census and analyzed using
a geographic information system. PRINCIPAL FINDINGS: In all, 25.8 percent of the
population in England lived in areas with a significant low GP accessibility
(mean z-score: -4.2); 27.6 percent lived in areas with a significant high GP
accessibility (mean z-score: 7.7); 97.8 percent of high GP accessibility areas
represented urban areas, and 31.1 percent of low GP accessibility areas
represented rural areas (correlation of accessibility and urbanity: r = 0.59;
p<.001). Furthermore, a minor negative correlation with social deprivation was
present (r = -0.19; p<.001). Results were confirmed by a multivariate analysis.
CONCLUSION: This study showed substantially differing GP accessibility throughout
England. However, socially deprived areas did not have poorer spatial access to
GPs.
PMID- 28685829
TI - A rare graft-versus-host disease-like thymoma-associated paraneoplastic
autoimmune multiorgan syndrome.
PMID- 28685828
TI - Food and nutrition security in the Hindu Kush Himalayan region.
AB - The status of food and nutrition security and its underlying factors in the Hindu
Kush Himalayan (HKH) region is investigated. In this region, one third to a half
of children (<5 years of age) suffer from stunting, with the incidence of wasting
and under-weight also being very high. The prevalence of stunting, wasting and
under-weight in children is particularly high in some mountain areas such as
Meghalaya state in India, the western mountains and far-western hills of Nepal,
Balochistan province in Pakistan, eastern Afghanistan, and Chin state in Myanmar.
Food habits in the HKH region are changing. This has led to a deterioration in
traditional mountain food systems with a decline in agrobiodiversity. Factors
such as high poverty and low dietary energy intakes, a lack of hygienic
environments, inadequate nutritional knowledge, and climate change and
environmental degradation are also influencing food and nutrition security in the
HKH region. To achieve sustainable food and nutrition security in the mountains,
this study suggests a multi-sectoral integrated approach with consideration of
nutritional aspects in all development processes dealing with economic, social,
agricultural and public health issues. (c) 2017 Society of Chemical Industry.
PMID- 28685830
TI - Treatment, short-term outcomes, and costs associated with larynx cancer care in
commercially insured patients.
AB - OBJECTIVES/HYPOTHESIS: To examine associations between treatment, complications,
and costs in patients with laryngeal cancer. STUDY DESIGN: Retrospective cross
sectional analysis of MarketScan Commercial Claim and Encounters data. METHODS:
We evaluated 10,969 patients diagnosed with laryngeal cancer from 2010 to 2012
using cross-tabulations and multivariate regression. RESULTS: Chemoradiation was
significantly associated with supraglottic tumors (relative risk ratio [RRR] =
5.9 [4.4-7.8]), pretreatment gastrostomy (RRR = 4.0 [2.7-6.1]), and alcohol abuse
(RRR = 0.5 [0.3-0.9]). Treatment-related complications occurred in 23% of
patients, with medical complications in 22% and surgical complications in 7%.
Chemoradiation (odds ratio [OR] = 3.7 [2.6-5.2]), major surgical procedures (OR =
4.9 [3.5-6.8]), reconstruction (OR = 7.7 (4.1-14.7)], and advanced comorbidity
(OR = 9.7 [5.7-16.5] were associated with acute complications.
Recurrent/persistent disease occurred in 23% of patients and was associated with
high-volume care (OR = 1.4 [1.1-1.8]). Salvage surgery was performed in 46% of
patients with recurrent/persistent disease and was less likely for supraglottic
disease (OR = 0.5 [0.4-0.8]) and after chemoradiation (OR = 0.4 [0.2-0.6]).
Initial treatment and 1-year overall costs for chemoradiation were higher than
all other treatment categories, after controlling for all other variables
including complications and salvage. High-volume care was associated with
significantly lower costs of care for surgical patients but was not associated
with differences in costs of care for nonoperative treatment. CONCLUSIONS: In
commercially insured patients <65 years old with laryngeal cancer, chemoradiation
was associated with increased costs, an increased likelihood of treatment-related
medical complications, and a reduced likelihood of surgical salvage. Higher
volume surgical care was associated with lower initial treatment and 1-year costs
of care. These data have implications for discussions of value and quality in an
era of healthcare reform. LEVEL OF EVIDENCE: 2c. Laryngoscope, 128:91-101, 2018.
PMID- 28685831
TI - Integrated analysis of SNP, CNV and gene expression data in genetic association
studies.
AB - Integrative approaches that combine multiple forms of data can more accurately
capture pathway associations and so provide a comprehensive understanding of the
molecular mechanisms that cause complex diseases. Association analyses based on
single nucleotide polymorphism (SNP) genotypes, copy number variant (CNV)
genotypes, and gene expression profiles are the 3 most common paradigms used for
gene set/pathway enrichment analyses. Many work has been done to leverage
information from 2 types of data from these 3 paradigms. However, to the best of
our knowledge, there is no work done before to integrate the 3 paradigms all
together. In this article, we present an integrated analysis that combine SNP,
CNV, and gene expression data to generate a single gene list. We present
different methods to compare this gene list with the other 3 possible lists that
result from the combinations of the following pairs of data: SNP genotype with
gene expression, CNV genotype with gene expression, and SNP genotype with CNV
genotype. The comparison is done using 3 different cancer datasets and 2
different methods of comparison. Our results show that integrating SNP, CNV, and
gene expression data give better association results than integrating any pair of
3 data.
PMID- 28685832
TI - Assessment of genotoxicity and biodistribution of nano- and micron-sized yttrium
oxide in rats after acute oral treatment.
AB - The increasing use of yttrium oxide (Y2 O3 ) nanoparticles (NPs) entails an
improved understanding of their potential impact on the environmental and human
health. In the present study, the acute oral toxicity of Y2 O3 NPs and their
microparticles (MPs) was carried out in female albino Wistar rats with 250, 500
and 1000 mg kg-1 body weight doses. Before the genotoxicity evaluation,
characterization of the particles by transmission electron microscopy, dynamic
light scattering and laser Doppler velocimetry was performed. The genotoxicity
studies were conducted using micronucleus and comet assays. Results showed that
Y2 O3 NP-induced significant DNA damage at higher dose (1000 mg kg-1 body weight)
in peripheral blood leukocytes and liver cells, micronucleus formation in bone
marrow and peripheral blood cells. The findings from biochemical assays depicted
significant alterations in aspartate transaminase, alanine transaminase, alkaline
phosphatase, malondialdehyde, superoxide dismutase, reduced glutathione, catalase
and lactate dehydrogenase levels in serum, liver and kidneys at the higher dose
only. Furthermore, tissue biodistribution of both particles was analyzed by
inductively coupled plasma optical emission spectrometry. Bioaccumulation of
yttrium (Y) in all tissues was significant and dose-, time- and organ-dependent.
Moreover, Y2 O3 NP-treated rats exhibited higher tissue distribution along with
greater clearance through urine whereas Y2 O3 MP-dosed animals depicted the
maximum amount of Y in the feces. Hence, the results indicated that
bioaccumulation of Y2 O3 NPs via its Y ions may induce genotoxic effects.
PMID- 28685833
TI - Reproductive biology of Psammobatis rutrum (Chondrichthyes: Arhynchobatidae) in
south Brazil, south-west Atlantic.
AB - This study presents information on the reproductive biology of Psammobatis rutrum
based on 55 males and 53 females obtained as by-catch from bottom trawlers off
southern Brazil during July 2013 and September 2014 and includes a detailed
description of the egg capsule. Total lengths (LT ) ranged from 22.3 to 31.6 cm
and most of the sample comprised larger individuals, although there were no
sexual differences in length-frequency distributions. Significant sexual
differences were found for total length-disc width, LT -body mass and LT
eviscerated body mass relationships, with females being heavier and larger. Males
started to mature at 25.5 cm LT and females, at 25.9 cm LT , while LT at maturity
was calculated in 26.67 and 26.81 cm, respectively. Attaining larger sizes and
mass may represent a reproductive investment for females, as observed in other
rajoid species. Egg bearing females were first observed over 27.1 cm LT and
ovarian fecundity was 1-12 vitellogenic follicles. The egg capsules were 2.22
2.62 cm length and had attaching fibrils on both lateral sides. Microscopically,
the ventral face of the egg capsule was rougher than the dorsal face.
PMID- 28685834
TI - Molecular survey of haemoplasmas in shelter dogs and associations with
Rhipicephalus sanguineus sensu lato.
AB - This study aimed to assess the occurrence of canine haemoplasma infection in
domestic dogs and its possible trans-stadial transmission by Rhipicephalus
sanguineus sensu lato (Ixodida: Ixodidae) in shelter dogs in Diyarbakir Province
in southeast Turkey. Blood samples (n = 282) collected from domestic dogs were
analysed by polymerase chain reaction (PCR) for the presence of canine
haemoplasma. Fully engorged nymphs (n = 204) were removed from dogs that were
positive for canine haemoplasma by PCR and maintained in an incubator at 28
degrees C for moulting. Unfed ticks (n = 2185) comprising 2100 nymphs and 85
adults collected from the grounds of the same shelter were also screened. Of 282
dogs, 108 [38.3%, 95% confidence interval (CI) 32.6-44.2] were PCR-positive for
canine haemoplasmas. Mycoplasma haemocanis (Mhc) infection (26.2%, 95% CI 21.2
31.8) was observed in a significantly higher number of dogs than was Candidatus
Mycoplasma haematoparvum (CMhp) infection (6.7%, 95% CI 4.1-10.3). Co-infections
were seen in 15 (5.3%, 95% CI 3.0-8.6) dogs. None of the tick specimens examined
were found to be positive for haemoplasma. Partial sequences of the 16S ribosomal
RNA (rRNA) gene shared 99-100% identity with the corresponding published
sequences for Mhc and CMhp. The present results revealed no trans-stadial
transmission of canine haemoplasma species by R. sanguineus s.l. in field
conditions.
PMID- 28685835
TI - Pharmacokinetics and tissue distribution of enrofloxacin after single
intramuscular injection in Pacific white shrimp.
AB - The pharmacokinetic properties and tissue distribution of enrofloxacin (EF) were
investigated after single intramuscular (i.m.) dose of 10 mg/kg body weight
(b.w.) in Pacific white shrimp at 22 to 25 degrees C. EF and its metabolite
ciprofloxacin (CF) were determined by high-performance liquid chromatography.
After i.m. administration, EF was absorbed quickly, and the peak of EF
concentration (Cmax ) reached at first time point in hemolymph. The volume of
distribution Vd(area) of EF was 3.84 L/kg, indicating that the distribution of EF
was good. The area under the concentration-time curve (AUC) of EF was 90.1 and
274.2 MUg hr/ml in muscle and hepatopancreas, respectively, which was higher than
75.8 MUg hr/ml in hemolymph. The EF elimination was slow in muscle and
hepatopancreas with the half-life (T1/2beta ) of 52.3 and 75.8 hr, respectively.
CF, the mainly metabolite of EF, was detected in hemolymph, muscle and
hepatopancreas. The Cmax was 0.030, 0.013 and 0.218 MUg/ml, respectively. Based
on a minimum inhibitory concentration (MIC) of 0.006-0.032 MUg/ml for susceptible
strains, EF i.m. injected at a dose 10 mg/kg could be efficacious against common
pathogenic bacteria of Pacific white shrimp.
PMID- 28685836
TI - The stability of the transcriptome during the estrous cycle in four regions of
the mouse brain.
AB - We analyzed the transcriptome of the C57BL/6J mouse hypothalamus, hippocampus,
neocortex, and cerebellum to determine estrous cycle-specific changes in these
four brain regions. We found almost 16,000 genes are present in one or more of
the brain areas but only 210 genes, ~1.3%, are significantly changed as a result
of the estrous cycle. The hippocampus has the largest number of differentially
expressed genes (DEGs) (82), followed by the neocortex (76), hypothalamus (63),
and cerebellum (26). Most of these DEGs (186/210) are differentially expressed in
only one of the four brain regions. A key finding is the unique expression
pattern of growth hormone (Gh) and prolactin (Prl). Gh and Prl are the only DEGs
to be expressed during only one stage of the estrous cycle (metestrus). To gain
insight into the function of the DEGs, we examined gene ontology and phenotype
enrichment and found significant enrichment for genes associated with
myelination, hormone stimulus, and abnormal hormone levels. Additionally, 61 of
the 210 DEGs are known to change in response to estrogen in the brain. 50 of the
210 genes differentially expressed as a result of the estrous cycle are related
to myelin and oligodendrocytes and 12 of the 63 DEGs in the hypothalamus are
oligodendrocyte- and myelin-specific genes. This transcriptomic analysis reveals
that gene expression in the female mouse brain is remarkably stable during the
estrous cycle and demonstrates that the genes that do fluctuate are functionally
related.
PMID- 28685838
TI - Do Undiagnosed Suicide Decedents Have Symptoms of a Mental Disorder?
AB - BACKGROUND: Psychological autopsy studies consistently report that the rate of
detected mental disorders among suicide decedents is below 100%. This implies
three possibilities: (a) a subset of suicide decedents did not have a mental
disorder at the time of death; (b) all suicide decedents suffered from a mental
disorder, but some were undetected due to methodological limitations; and/or (c)
suicide decedents with an undetected mental disorder displayed significant and
perhaps subclinical features of a mental disorder. OBJECTIVE: In this article, we
examined these possibilities by evaluating the differences in symptoms and
stressors between suicide decedents who were undiagnosed and those diagnosed with
a mental disorder at the time of death. METHOD: We reviewed 130 case studies of
community-based suicide decedents originally described in Robins' (1981)
psychological autopsy study. RESULTS: Without exception, suicide decedents in
Robins' sample suffered either from a clearly diagnosable mental disorder or
displayed features indicative of a significant, even if subclinical, presentation
of a mental disorder. Undiagnosed and diagnosed suicide decedents did not
significantly differ with regards to demographics, violence of suicide method,
suicide attempt history, the number and intensity of stressful life events
preceding death, and whether their death was a murder-suicide. CONCLUSION:
Although clearly not all who suffer from mental disorders will die by suicide,
these findings imply that all who die by suicide appear to exhibit, at minimum,
subclinical psychiatric symptoms with the great majority showing prominent
clinical symptoms. We conclude with clinical implications and recommendations for
future study.
PMID- 28685839
TI - Lipoid proteinosis: A case with distinct histopathological and radiological
findings.
AB - Lipoid proteinosis is a rare inherited genodermatosis characterized by hyaline
deposits in various tissues. Clinically, it manifests with cutaneous as well as
extracutaneous features. Periodic acid-Schiff (PAS)-reactive hyaline deposits in
the upper dermis, with localization around blood vessels and eccrine sweat
glands, in particular, is the histopathological hallmark finding. On brain
imaging, bilateral symmetrical temporal lobe calcifications are considered to be
pathognomonic of this disorder. We report a case of lipoid proteinosis in which
hyaline deposits were present in the papillary and reticular dermis, without
being seen at the periphery of eccrine sweat glands, along with dystrophic
calcification. Magnetic resonance imaging (MRI) of brain revealed hydrocephalus,
subependymal heterotropia and absent splenium of corpus callosum with no evidence
of temporal lobe calcification. Thus, our case highlights the inherent diverse
nature of lipoid proteinosis.
PMID- 28685837
TI - Proteomic analyses of nucleus laminaris identified candidate targets of the
fragile X mental retardation protein.
AB - The avian nucleus laminaris (NL) is a brainstem nucleus necessary for binaural
processing, analogous in structure and function to the mammalian medial superior
olive. In chickens (Gallus gallus), NL is a well-studied model system for
activity-dependent neural plasticity. Its neurons have bipolar extension of
dendrites, which receive segregated inputs from two ears and display rapid and
compartment-specific reorganization in response to unilateral changes in auditory
input. More recently, fragile X mental retardation protein (FMRP), an RNA-binding
protein that regulates local protein translation, has been shown to be enriched
in NL dendrites, suggesting its potential role in the structural dynamics of
these dendrites. To explore the molecular role of FMRP in this nucleus, we
performed proteomic analysis of NL, using micro laser capture and liquid
chromatography tandem mass spectrometry. We identified 657 proteins, greatly
represented in pathways involved in mitochondria, translation and metabolism,
consistent with high levels of activity of NL neurons. Of these, 94 are potential
FMRP targets, by comparative analysis with previously proposed FMRP targets in
mammals. These proteins are enriched in pathways involved in cellular growth,
cellular trafficking and transmembrane transport. Immunocytochemistry verified
the dendritic localization of several proteins in NL. Furthermore, we confirmed
the direct interaction of FMRP with one candidate, RhoC, by in vitro RNA binding
assays. In summary, we provide a database of highly expressed proteins in NL and
in particular a list of potential FMRP targets, with the goal of facilitating
molecular characterization of FMRP signaling in future studies.
PMID- 28685840
TI - European LeukemiaNet study on the reproducibility of bone marrow features in
masked polycythemia vera and differentiation from essential thrombocythemia.
AB - The purpose of the study was to assess consensus and interobserver agreement
among an international panel of six hematopathologists regarding characterization
and reproducibility of bone marrow (BM) histologic features used to diagnose
early stage myeloproliferative neoplasms, in particular differentiation of so
called masked/prodromal polycythemia vera (mPV) from JAK2-mutated essential
thrombocythemia (ET). The six members of the hematopathology panel evaluated 98
BM specimens independently and in a blinded fashion without knowledge of clinical
data. The specimens included 48 cases of mPV according to the originally
published hemoglobin threshold values for this entity (male: 16.0-18.4 g/dL,
female: 15.0-16.4 g/dL), 31 cases with overt PV according to the updated 2016 WHO
criteria, and 19 control cases. The latter group included cases of JAK2-mutated
ET, primary myelofibrosis, myelodysplastic syndrome, and various reactive
conditions. Inter-rater agreement between the panelists was very high (overall
agreement 92.6%, kappa 0.812), particularly with respect to separating mPV from
ET. Virtually all cases of mPV were correctly classified as PV according to their
BM morphology. In conclusion, a central blinded review of histology slides by six
hematopathologists demonstrated that highly reproducible specific histological
pattern characterize PV and confirmed the notion that there are no significant
differences between mPV and overt PV in relation to BM morphology.
PMID- 28685841
TI - Krebs cycle rewired for macrophage and dendritic cell effector functions.
AB - The Krebs cycle is an amphibolic pathway operating in the mitochondrial matrix of
all eukaryotic organisms. In response to proinflammatory stimuli, macrophages and
dendritic cells undergo profound metabolic remodelling to support the
biosynthetic and bioenergetic requirements of the cell. Recently, it has been
discovered that this metabolic shift also involves the rewiring of the Krebs
cycle to regulate cellular metabolic flux and the accumulation of Krebs cycle
intermediates, notably, citrate, succinate and fumarate. Interestingly, a new
role for Krebs cycle intermediates as signalling molecules and immunomodulators
that dictate the inflammatory response has begun to emerge. This review will
discuss the latest developments in Krebs cycle rewiring and immune cell effector
functions, with a particular focus on the regulation of cytokine production.
PMID- 28685842
TI - Two Models of Moral Judgment.
AB - This paper compares two theories and their two corresponding computational models
of human moral judgment. In order to better address psychological realism and
generality of theories of moral judgment, more detailed and more psychologically
nuanced models are needed. In particular, a motivationally based theory of moral
judgment (and its corresponding computational model) is developed in this paper
that provides a more accurate account of human moral judgment than an existing
emotion-reason conflict theory. Simulations based on the theory capture and
explain a range of relevant human data. They account not only for the original
data that were used to support the emotion-reason conflict theory, but also for a
wider range of data and phenomena.
PMID- 28685843
TI - Oxidative stress management in the hair follicle: Could targeting NRF2 counter
age-related hair disorders and beyond?
AB - Widespread expression of the transcription factor, nuclear factor (erythroid
derived 2)-like 2 (NRF2), which maintains redox homeostasis, has recently been
identified in the hair follicle (HF). Small molecule activators of NRF2 may
therefore be useful in the management of HF pathologies associated with redox
imbalance, ranging from HF greying and HF ageing via androgenetic alopecia and
alopecia areata to chemotherapy-induced hair loss. Indeed, NRF2 activation has
been shown to prevent peroxide-induced hair growth inhibition. Multiple
parameters can increase the levels of reactive oxygen species in the HF, for
example melanogenesis, depilation-induced trauma, neurogenic and autoimmune
inflammation, toxic drugs, environmental stressors such as UV irradiation,
genetic defects and aging-associated mitochondrial dysfunction. In this review,
the potential mechanisms whereby NRF2 activation could prove beneficial in
treatment of redox-associated HF disorders are therefore discussed.
PMID- 28685844
TI - Genetic characterization of GSD I in Serbian population revealed unexpectedly
high incidence of GSD Ib and 3 novel SLC37A4 variants.
AB - Glycogen storage disease (GSD) type I is inborn metabolic disease characterized
by accumulation of glycogen in multiple organs. We analyzed 38 patients with
clinical suspicion of GSD I using Sanger and next-generation sequencing (NGS). We
identified 28 GSD Ib and 5 GSD Ia patients. In 5 patients, GSD III, VI, IX,
cholesteryl-ester storage disease and Shwachman-Diamond syndrome diagnoses were
set using NGS. Incidences for GSD Ia and GSD Ib were estimated at 1:172 746 and
1:60 461 live-births, respectively. Two variants were identified in G6PC gene:
c.247C>T (p.Arg83Cys) and c.518T>C (p.Leu173Pro). In SLC37A4 gene, 6 variants
were detected. Three previously reported variants c.81T>A (p.Asn27Lys), c.162C>A
(p.Ser54Arg) and c.1042_1043delCT (p.Leu348Valfs*53) accounted for 87% of all
analyzed alleles. Computational, transcription studies and/or clinical
presentation in patients confirmed pathogenic effect of 3 novel variants:
c.248G>A (p.Gly83Glu), c.404G>A (p.Gly135Asp) and c.785G>A (p.Ser263Glyfs*33 or
p.Gly262Asp). In the cohort, hepatomegaly, hypoglycemia and failure to thrive
were the most frequent presenting signs of GSD Ia, while hepatomegaly and
recurrent bacterial infections were clinical hallmarks of GSD Ib. All GSD Ib
patients developed neutropenia while 20.6% developed inflammatory bowel disease.
Our study revealed the highest worldwide incidence of GSD Ib. Furthermore,
description of 3 novel variants will facilitate medical genetic practice.
PMID- 28685845
TI - Restructured low-fat cooked ham containing liquid whey fortified with lactulose.
AB - BACKGROUND: Current health concerns have driven consumers to request products
with nutritional and physiological advantages, which can be achieved by using
prebiotic ingredients. Lactulose is a prebiotic with excellent functional
properties and can be easily incorporated into meat products through the addition
of liquid whey. This study investigated the technological and sensorial quality
of restructured cooked ham elaborated without liquid whey added (control) and
with liquid whey containing different contents (0, 30, 60 and 100 g kg-1 ) of
lactulose. RESULTS: Liquid whey did not change any technological or sensorial
characteristics of the product, but the general acceptability decreased due to
addition of lactulose. Samples with higher lactulose concentrations had lower
moisture content, pH and refreezing loss and increased carbohydrate content.
Control and whey added samples had higher lightness and lower intense color than
samples with lactulose. Liquid whey additions with higher lactulose content
increased hardness and chewiness of the samples. CONCLUSION: Restructured cooked
hams formulated with liquid whey and 30 g kg-1 of lactulose had minimal effects
on the technological properties and sensory characteristics and, due to the
possible benefits conferred by the prebiotic, is a potential alternative to
provide meat products with prebiotic activity. (c) 2017 Society of Chemical
Industry.
PMID- 28685846
TI - Description of late onset neutropenia in indolent lymphoma patients treated with
bendamustine plus rituximab.
AB - Bendamustine (B) associated with rituximab (R) is widely described in literature
for the management of patients with chronic lymphoid leukaemia (CLL) and indolent
non-Hodgkin lymphoma. Safety data regarding late hematotoxicity such as late
onset neutropenia (LON) are scarce. The aim of our study was to assess the
incidence and to identify risk factors for LON in patients with indolent non
Hodgkin lymphoma and CLL treated with B and R (B-R). One hundred forty five
patients were treated with B-R as first or second line. Patients with neutropenia
prior induction treatment, treated beyond second line and relapsing within 3
months after the end of induction treatment, were excluded. Patients receiving at
least 1 cycle of B-R and having LON during follow-up period were included and
considered as eligible for toxicity assessment. A complete blood count was
performed 4 weeks after the last cycle of induction treatment and thereafter
every 3 months for 1 year. Thirty six patients were identified in our cohort
(incidence of 25%), mostly affected by CLL (n = 11) and follicular lymphoma (FL)
(n = 15). During follow-up, 84 events of LON were recorded, 61% and 39% were of
grades 1/2 and 3/4, respectively. No episode of febrile neutropenia was
documented. Amongst 13 of the 15 patients with FL undergoing R maintenance, 8 had
treatment discontinuation because of LON. Median time for LON (grade > 2) and
time to recovery (grade < 3) were of 11.2 and 17.3 weeks, respectively. One year
after B-R induction, LON persisted in 4 patients. The risk of LON was increased
both in patients with FL or CLL and performance status >1. The LON in B-R treated
patients is clinically relevant. Close clinical and biological follow-up and
treatment prophylaxis (eg, valaciclovir and cotrimoxazole) especially for FL
patients undergoing maintenance with R monotherapy seems relevant.
PMID- 28685847
TI - MicroRNA-300 promotes apoptosis and inhibits proliferation, migration, invasion
and epithelial-mesenchymal transition via the Wnt/beta-catenin signaling pathway
by targeting CUL4B in pancreatic cancer cells.
AB - The study aims to verify the hypothesis that up-regulation of microRNA-300 (miR
300) targeting CUL4B promotes apoptosis and suppresses proliferation, migration,
invasion, and epithelial-mesenchymal transition (EMT) of pancreatic cancer cells
by regulating the Wnt/beta-catenin signaling pathway. Pancreatic cancer tissues
and adjacent tissues were collected from 110 pancreatic cancer patients.
Expression of miR-300, CUL4B, Wnt, beta-catenin, E-cadherin, N-cadherin, Snail,
GSK-3beta, and CyclinD1 were detected using qRT-PCR and Western blot. CFPAC-1,
Capan-1, and PANC-1 were classified into blank, negative control (NC), miR-300
mimics, miR-300 inhibitors, siRNA-CUL4B, and miR-300 inhibitors + siRNA-CUL4B
groups. The proliferation, migration, invasion abilities, the cell cycle
distribution, and apoptosis rates were measured in CCK-8 and Transwell assays.
Pancreatic cancer tissues showed increased CUL4B expression but decreased miR-300
expression. When miR-300 was lowly expressed, CUL4B was upregulated which in-turn
activated the Wnt/beta-catenin pathway to protect the beta-catenin expression and
thus induce EMT. When miR-300 was highly expressed, CUL4B was downregulated which
in-turn inhibited the Wnt/beta-catenin pathway to prevent EMT. Weakened cell
migration and invasion abilities and enhanced apoptosis were observed in the
CUL4B group. The miR-300 inhibitors group exhibited an evident increase in growth
rate accompanied the largest tumor volume. Smaller tumor volume and slower growth
rate were observed in the miR-300 mimics and siRNA-CUL4B group. Our study
concludes that lowly expressed miR-300 may contribute to highly expressed CUL4B
activating the Wnt/beta-catenin signaling pathway and further stimulating EMT,
thus promoting proliferation and migration but suppressing apoptosis of
pancreatic cancer cells.
PMID- 28685848
TI - Learning Object Names at Different Hierarchical Levels Using Cross-Situational
Statistics.
AB - Objects in the world usually have names at different hierarchical levels (e.g.,
beagle, dog, animal). This research investigates adults' ability to use cross
situational statistics to simultaneously learn object labels at individual and
category levels. The results revealed that adults were able to use co-occurrence
information to learn hierarchical labels in contexts where the labels for
individual objects and labels for categories were presented in completely
separated blocks, in interleaved blocks, or mixed in the same trial. Temporal
presentation schedules significantly affected the learning of individual object
labels, but not the learning of category labels. Learners' subsequent
generalization of category labels indicated sensitivity to the structure of
statistical input.
PMID- 28685849
TI - Support of the nurse.
AB - AIM: A multidisciplinary concept analysis of support of the nurse. BACKGROUND:
Nurses provide support on a daily basis to their patients and this aspect of
support has been well established in current literature, yet support of the nurse
rather than from the nurse is not readily established in recent research. The
gaps in the analysis of support of nurses are addressed from a multidisciplinary
approach. METHODS: Using the Walker and Avant's method, a concept analysis of
support of the nurse was conducted. Electronic databases (CINAHL, MedLine, and
PyscINFO) were searched using the terms support, concept analysis, and nurse. Of
the 27 articles found in the search, only seven articles met the inclusion
criterion of nurse as primary subject matter. RESULTS: The three defining
attributes of support are a safe environment, connection, and communication.
Antecedents of support include accessibility and information. Consequences of
support are relationships formed and empowerment. The empirical referent
highlighted in current literature is the Multidimensional Scale of Perceived
Social Support. CONCLUSION: While the support that nurses provide to patients has
been studied for years, there is a lack of studies addressing the concept of
support of nurses. Future research could fill this gap by investigating support
of nurses in holistic ways, such as qualitative or mixed-method analysis. Support
is not always accessible in a face to face format, so mobile and web options are
presented as possible interventional opportunities to meet nurses at the bedside.
PMID- 28685850
TI - Return-on-Investment (ROI) Analyses of an Inpatient Lay Health Worker Model on 30
Day Readmission Rates in a Rural Community Hospital.
AB - PURPOSE: The purpose of the study was to assess the return-on-investment (ROI) of
an inpatient lay health worker (LHW) model in a rural Appalachian community
hospital impacting 30-day readmission rates. METHODS: The Bridges to Home (BTH)
study completed an evaluation in 2015 of an inpatient LHW model in a rural
Kentucky hospital that demonstrated a reduction in 30-day readmission rates by
47.7% compared to a baseline period. Using the hospital's utilization and
financial data, a validated ROI calculator specific to care transition programs
was used to assess the ROI of the BTH model comparing 3 types of payment models
including Diagnosis Related Group (DRG)-only payments, pay-for-performance (P4P)
contracts, and accountable care organizations (ACOs). FINDINGS: The BTH program
had a -$0.67 ROI if the hospital had only a DRG-based payment model. If the
hospital had P4P contracts with payers and 0.1% of its annual operating revenue
was at risk, the ROI increased to $7.03 for every $1 spent on the BTH program.
However, if the hospital was an ACO as was the case for this study's community
hospital, the ROI significantly increased to $38.48 for every $1 spent on the BTH
program. CONCLUSIONS: The BTH model showed a viable ROI to be considered by
community hospitals that are part of an ACO or P4P program. A LHW care transition
model may be a cost-effective alternative for impacting excess 30-day
readmissions and avoiding associated penalties for hospital systems with a value
based payment model.
PMID- 28685851
TI - Risk of cutaneous T-cell lymphoma in patients with chronic lymphocytic leukemia
and other subtypes of non-Hodgkin lymphoma.
AB - BACKGROUND: Second hematologic cancers in patients with chronic lymphocytic
leukemia/small lymphocytic lymphoma (CLL) are well documented and include Hodgkin
lymphoma, therapy-related acute myeloid leukemia/myelodysplastic syndromes, and
transformation to diffuse large B-cell lymphoma. Although cutaneous T-cell
lymphoma (CTCL) has been reported in patients with CLL, the incidence and
comparison to expected rates are unknown. We evaluated the incidence of CTCL
among patients with CLL or other non-Hodgkin lymphoma (NHL) subtypes using data
from the Surveillance, Epidemiology, and End Results (SEER) Program. METHODS: We
searched the SEER 13 registries for patients with a diagnosis of CLL and NHL
between 1992 and 2008. Among patients identified, we evaluated the incidence of
CTCL. RESULTS: Among 31,286 patients with CLL, the incidence of CTCL was not
significantly higher in men than women: 104.2 (95% CI, 50.0-191.8) and 28.1 (95%
CI, 3.4-101.3) per 1,000,000 person-years, respectively (P = 0.06). Among 97,691
patients with NHL, the incidence of CTCL was similar in men and women (97.9 [95%
CI, 62.0-146.9] and 92.0 [95% CI, 56.2-142.1] per 1,000,000 person-years,
respectively; P = 0.84). The incidence of CTCL among males with CLL (standardized
incidence ratio [SIR], 3.0 [95% CI, 1.4-5.5]), males with NHL (SIR, 3.7 [95% CI,
2.3-5.5]), and females with NHL (SIR, 5.9 [95% CI, 3.6-9.1]) was significantly
higher than expected in the general population (all P < 0.001). CONCLUSION: The
risk of CTCL is greater in men with CLL than in the general population. In
patients with NHL, both men and women are at greater risk for CTCL than in the
general population.
PMID- 28685852
TI - The Relationship Between Rural Health Clinic Use and Potentially Preventable
Hospitalizations and Emergency Department Visits Among Medicare Beneficiaries.
AB - PURPOSE: High rates of potentially preventable hospitalizations and emergency
department (ED) visits indicate limited primary care access. Rural Health Clinics
(RHCs) are intended to increase access to primary care. The goal of this study
was to evaluate the role of RHCs and their impact on potentially preventable
hospitalizations and ED visits among Medicare beneficiaries based on actual
individual-level utilization patterns. METHODS: With Medicare Part A and Part B
claims data from 2007 to 2010, we constructed a series of individual-level
negative binomial regression models to examine the relationship between RHC use
and the number of potentially preventable hospitalizations and ED visits.
FINDINGS: RHC use was associated with a 27% increase in potentially preventable
hospitalizations and a 24% increase in potentially preventable ED visits among
older Medicare enrollees. Among younger, disabled Medicare beneficiaries, RHC use
was associated with a 14% increase in potentially preventable hospitalizations
and an 18% increase in potentially preventable ED visits. Potentially preventable
hospitalizations and ED visits were more common among beneficiaries who were
black or who had more chronic conditions. CONCLUSIONS: The results of our study
highlight that the Medicare population using RHCs is at especially high risk for
potentially preventable hospitalizations and ED visits. The mechanisms behind
this are not well understood and should receive continued attention from policy
makers and researchers.
PMID- 28685853
TI - Developing an interdisciplinary and cross-sectoral community of practice in the
domain of forests and livelihoods.
AB - Although significant resources are being spent researching and fostering the
relationship between forests and livelihoods to promote mutually beneficial
outcomes, critical gaps in understanding persist. A core reason for such gaps is
that researchers, practitioners, and policy makers lack the structured space to
interact and collaborate, which is essential for effective, interdisciplinary
research, practice, and evaluation. Thus, scientific findings, policy
recommendations, and measured outcomes have not always been synthesized into
deep, systemic understanding; learning from practice and implementation does not
easily find its way into scientific analyses, and science often fails to
influence policy. Communities of practice (CofPs) are dynamic sociocultural
systems that bring people together to share and create knowledge around a common
topic of interest. They offer participants a space and structure within which to
develop new, systemic approaches to multidimensional problems on a common theme.
Uniquely informed by a systems-thinking perspective and drawing from the
scientific and gray literatures and in-depth interviews with representatives of
established CofPs in the natural resource management and development domain, we
argue that a well-designed and adequately funded CofP can facilitate
interdisciplinary and cross-sectoral relationships and knowledge exchange. Well
designed CofPs integrate a set of core features and processes to enhance
individual, collective, and domain outcomes; they set out an initial but evolving
purpose, encourage diverse leadership, and promote collective-identity
development. Funding facilitates effective communication strategies (e.g., in
person meetings). We urge our colleagues across sectors and disciplines to take
advantage of CofPs to advance the domain of forests and livelihoods.
PMID- 28685854
TI - Digest: Shifting biomes: Insight into patterns of plant radiation and dispersal.
PMID- 28685855
TI - Alcohol exposure during pregnancy altered childhood developmental trajectories in
a rural South African community.
AB - AIM: This study examined the effects of prenatal alcohol exposure on childhood
development trajectories in a rural South African community between 2003 and
2008. METHODS: We assessed 121 children at 7-12 months (year one) and 5-6 years
(year five) using the Griffiths Mental Developmental Scales - Extended Revised,
which measures sensorimotor, cognitive and social development, with lower scores
indicating developmental delay. We also interviewed their mothers or caregivers.
Three groups were identified: 29 with foetal alcohol syndrome (FAS) or partial
FAS (pFAS), 57 more who had been exposed to alcohol and 35 controls who had not.
RESULTS: The scale's total score was higher in the controls than in the FAS/pFAS
group at year one and year five and in the alcohol-exposed group at year five.
Many groups' trajectories declined when compared with global norms, but the
trajectories in the FAS/pFAS and the alcohol-exposed groups declined more than
the controls for eye-hand and performance and total score. Earlier pregnancy
recognition in the FAS/pFAS group correlated strongly (r = -0.77) with higher GQ
in year five. CONCLUSION: FAS/pFAS and prenatal alcohol exposure affected the
Griffiths scores more than the control group. Efforts are needed to detect
pregnancy early and reduce alcohol exposure.
PMID- 28685856
TI - The performance of a resazurin chromogenic agar plate with a combined disc method
for rapid screening of extended-spectrum-beta-lactamases, AmpC beta-lactamases
and co-beta-lactamases in Enterobacteriaceae.
AB - A promising means of rapid screening of extended-spectrum-beta-lactamase (ESBL),
AmpC beta-lactamase, and co-production of ESBL and AmpC that combines resazurin
chromogenic agar (RCA) with a combined disc method is here reported. Cefpodoxime
(CPD) discs with and without clavulanic acid (CA), cloxacillin (CX) and CA+CX
were evaluated against 86 molecularly confirmed beta-lactamase-producing
Enterobacteriaceae, including 15 ESBLs, 32 AmpCs, nine co-producers of ESBL and
AmpC and 30 carbapenemase producers. The CA and CX synergy test successfully
detected all ESBL producers (100% sensitivity and 98.6% specificity) and all AmpC
producers (100% sensitivity and 96.36% specificity). This assay also performed
well in screening for co-existence of ESBL and AmpC (88.89% sensitivity and 100%
specificity). The RCA assay is simple and inexpensive and provides results within
7 hr. It can be performed in any microbiological laboratory, in particular, in
geographic regions in which ESBL, AmpC or co-beta-lactamase-producing
Enterobacteriaceae are endemic.
PMID- 28685857
TI - Biomechanical simulations of costo-vertebral and anterior vertebral body tethers
for the fusionless treatment of pediatric scoliosis.
AB - Compression-based fusionless tethers are an alternative to conventional surgical
treatments of pediatric scoliosis. Anterior approaches place an anterior (ANT)
tether on the anterolateral convexity of the deformed spine to modify growth.
Posterior, or costo-vertebral (CV), approaches have not been assessed for
biomechanical and corrective effectiveness. The objective was to biomechanically
assess CV and ANT tethers using six patient-specific, finite element models of
adolescent scoliotic patients (11.9 +/- 0.7 years, Cobb 34 degrees +/- 10
degrees ). A validated algorithm simulated the growth and Hueter-Volkmann growth
modulation over a period of 2 years with the CV and ANT tethers at two initial
tensions (100, 200 N). The models without tethering also simulated deformity
progression with Cobb angle increasing from 34 degrees to 56 degrees , axial
rotation 11 degrees to 13 degrees , and kyphosis 28 degrees to 32 degrees
(mean values). With the CV tether, the Cobb angle was reduced to 27 degrees and
20 degrees for tensions of 100 and 200 N, respectively, kyphosis to 21 degrees
and 19 degrees , and no change in axial rotation. With the ANT tether, Cobb was
reduced to 32 degrees and 9 degrees for 100 and 200 N, respectively, kyphosis
unchanged, and axial rotation to 3 degrees and 0 degrees . While the CV tether
mildly corrected the coronal curve over a 2-year growth period, it had sagittal
lordosing effect, particularly with increasing initial axial rotation (>15
degrees ). The ANT tether achieved coronal correction, maintained kyphosis, and
reduced the axial rotation, but over-correction was simulated at higher initial
tensions. This biomechanical study captured the differences between a CV and ANT
tether and indicated the variability arising from the patient-specific
characteristics. (c) 2017 Orthopaedic Research Society. Published by Wiley
Periodicals, Inc. J Orthop Res 36:254-264, 2018.
PMID- 28685858
TI - Diagnostic performance of routine esophagogastroduodenoscopy using magnifying
endoscope with narrow-band imaging for gastric cancer.
AB - BACKGROUND AND AIM: In Japan, an increase in the number of routine
esophagogastroduodenoscopy procedures is expected because several studies have
reported that endoscopy screening has reduced gastric cancer mortality.
Magnifying narrow-band imaging has been reported to be effective for accurate
diagnosis of gastric abnormalities such as cancers, adenomas, and intestinal
metaplasia. However, the efficacy of this method in routine
esophagogastroduodenoscopy has not been clarified. METHODS: We divided 3763
patients into two groups. The non-magnification group included 1842 patients who
underwent endoscopy screening using GIF-H260/LUCERA-SPECTRUM between October 2014
and February 2015, whereas the magnification group included 1921 patients who
underwent screening using GIF-H290Z/LUCERA-ELITE between March 2015 and May 2015.
In the magnification group, diagnosis of cancer was conducted using the VS
classification system. We did not carry out a biopsy when results were confirmed
as non-cancer using magnifying narrow-band imaging. If cancer was diagnosed, or
when a cancer or non-cancer diagnosis was difficult, we carried out a biopsy. We
analyzed and compared the diagnostic performance between the two groups. RESULTS:
Gastric biopsy rate was significantly lower in the magnification group (29%) than
in the non-magnification group (41%) (P < 0.001). Positive predictive value (PPV)
for gastric cancer was significantly higher in the magnification group (5.5%)
than in the non-magnification group (2.5%) (P < 0.001). Furthermore, PPV for
gastric epithelial neoplasia was significantly higher in the magnification group
(7.9%) than in the non-magnification group (3.2%) (P < 0.001). CONCLUSION:
Magnifying narrow-band imaging improves the diagnostic performance of routine
esophagogastroduodenoscopy.
PMID- 28685859
TI - Bird-community responses to habitat creation in a long-term, large-scale natural
experiment.
AB - Ecosystem function and resilience are compromised when habitats become fragmented
due to land-use change. This has led to national and international conservation
strategies aimed at restoring habitat extent and improving functional
connectivity (i.e., maintaining dispersal processes). However, biodiversity
responses to landscape-scale habitat creation and the relative importance of
spatial and temporal scales are poorly understood, and there is disagreement over
which conservation strategies should be prioritized. We used 160 years of
historic post-agricultural woodland creation as a natural experiment to evaluate
biodiversity responses to habitat creation in a landscape context. Birds were
surveyed in 101 secondary, broadleaf woodlands aged 10-160 years with >=80%
canopy cover and in landscapes with 0-17% broadleaf woodland cover within 3000 m.
We used piecewise structural equation modeling to examine the direct and indirect
relationships between bird abundance and diversity, ecological continuity, patch
characteristics, and landscape structure and quantified the relative conservation
value of local and landscape scales for bird communities. Ecological continuity
indirectly affected overall bird abundance and species richness through its
effects on stand structure, but had a weaker influence (effect size near 0) on
the abundance and diversity of species most closely associated with woodland
habitats. This was probably because woodlands were rapidly colonized by woodland
generalists in <=10 years (minimum patch age) but were on average too young
(median 50 years) to be colonized by woodland specialists. Local patch
characteristics were relatively more important than landscape characteristics for
bird communities. Based on our results, biodiversity responses to habitat
creation depended on local- and landscape-scale factors that interacted across
time and space. We suggest that there is a need for further studies that focus on
habitat creation in a landscape context and that knowledge gained from studies of
habitat fragmentation and loss should be used to inform habitat creation with
caution because the outcomes are not necessarily reciprocal.
PMID- 28685860
TI - Exercise-mediated modulation of autophagy in skeletal muscle.
AB - Although exercise exerts multiple beneficial health effects, it may also damage
cellular structures. Damaged elements are continuously degraded and its
constituents recycled to produce renovated structures through a process called
autophagy, which is essential for the adaptation to training. Autophagy is
particularly active in skeletal muscle, where it can be evaluated using specific
molecular markers of activation (unc-51-like kinase 1 [ULK1] phosphorylation) and
specific proteins indicating increased autophagosome content (increased total
LC3, LC3-II, LC3-II/LC3-I ratio). Studies in humans are technically limited but
have provided evidence suggesting the activation of autophagy in skeletal muscle
through AMP-activated protein kinase (AMPK) and its downstream target ULK1.
Autophagy activation is more likely when the intensity is elevated and the
exercise performed in the fasted state. The autophagy-gene program and
autophagosome content are upregulated after ultraendurance running competitions.
However, autophagosome content is reduced after endurance exercise at moderate
intensities (50% and 70% of VO2 max) for 60-120 minutes. Autophagosome content is
decreased within the first few hours after resistance training. The effects of
regular endurance and strength training on basal autophagy remain to be
established in humans. One study has reported that acute severe hypoxia increases
autophagosome content in human skeletal muscle, which is reverted by 20 minutes
of low-intensity exercise. Experiments with transgenic mice have shown that
autophagy is necessary for skeletal muscle adaptation to training. Little is
known on how genetic factors, environment, nutrition, drugs and diseases may
interact with exercise to modulate autophagy at rest and during exercise in
humans.
PMID- 28685862
TI - Sprint mechanics evaluation using inertial sensor-based technology: A laboratory
validation study.
AB - Advances in micro-electromechanical systems have turned magnetic inertial
measurement units (MIMUs) into a suitable tool for vertical jumping biomechanical
evaluation. Thus, this study aimed to determine whether appropriate reliability
and agreement reports could also be obtained when analyzing 20-m sprint
mechanics. Four bouts of 20-m sprints were evaluated to determine whether the
data provided by a MIMU placed at the lumbar spine could reliably assess sprint
mechanics and to examine the validity of the MIMU sensor compared to force plate
recordings. Maximal power (P0 ), force (F0 ), and velocity (V0 ), as well as
other mechanical determinants of sprint performance associated with the force
velocity, power-velocity, and ratio of forces-velocity, such as applied
horizontal force loss (Sfv ) and decrease in ratio of forces (Drf ), were
calculated and compared between instrumentations. Extremely large-to-very large
correlation levels between MIMU sensor-based sprint mechanics variables and force
plate recordings were obtained (mean+/-SD, force plate vs MIMU; V0, 8.61+/-0.85
vs 8.42+/-0.69; F0 , 383+/-110 vs 391+/-103; P0 , 873+/-246 vs 799+/-241; Sfv,
44.6+/-12.7 vs -46.2+/-10.7), ranging from 0.88 to 0.94, except for Drf, which
showed weak-to-moderate correlation level (r=.45; -6.32+/-1.08 vs -5.76+/-0.68).
Step-averaged force values measured with both systems were highly correlated
(r=.88), with a regression slope close to the identity (1.01). Bland and Altman
graphical representation showed a no random distribution of measured force
values. Finally, very large-to-extremely large retest correlation coefficients
were found for the intertrial reliability of MIMU measurements of sprint
performance variables (r value ranging from .72 to .96). Therefore, MIMUs showed
appropriate validity and reliability values for 20-m sprint performance
variables.
PMID- 28685861
TI - Suction blister lesions and epithelialization monitored by optical coherence
tomography.
AB - BACKGROUND/PURPOSE: Our objective was to assess epithelialization of suction
blister lesions by optical coherence tomography (OCT) and benchmark it to
histology using epidermal thickness (ET) as the primary outcome. METHODS: Thirty
two healthy volunteers were recruited to Study 1 and 2. One 10-mm suction blister
was raised on each buttock, and the blister roof was excised. Lesions were
covered with moisture-retaining dressing. In Study 1, the lesions were OCT
scanned on day 0 (D0), D2 and D4 and excised for histological examination. In
Study 2, the progress of epithelialization and skin barrier function were
monitored to D14. RESULTS: ET increased from D0 to D2 by 46 MUm (P<.001) and from
D2 to D4 by 19 MUm (P=.004). Compared with histology, OCT overestimated the
presence of the epithelium (P<.0001) and ET on D4. Reliable measurements were
obtained when the ET of the lesions reached the ET of the normal epidermis from
D5-D7 and onwards. The ET development was reflected in decreased transepidermal
water loss. CONCLUSION: We found that the OCT technique was poorly discriminative
with respect to the neoepithelium and the moist lesion surface material in the
early postinjury period. In the later stages, OCT seemed valuable for estimating
the advancement of epithelialization.
PMID- 28685863
TI - Efficacy and tolerability of the histone deacetylase inhibitor panobinostat in
clinical practice.
AB - The histone deacetylase inhibitor panobinostat has shown efficacy in phase-II and
phase-III trials for multiple myeloma and has recently received market approval
in combination with bortezomib and dexamethasone. Here, we retrospectively report
our single center experience with panobinostat/bortezomib/dexamethasone (FVD) in
a heavily pretreated patient population (n = 24) with a high degree of
refractoriness to proteasome inhibitors (PI) and immunomodulatory drugs (IMiD).
Median age was 67 years (range 49-87) and the median number of prior therapies
was 5 (range 2-17). Fourteen patients (58%) had high-risk cytogenetic
aberrations. Thirteen (54%) and 21 (88%) patients were refractory to PIs and
IMiDs, respectively. Twelve patients (50%) were refractory to bortezomib and 7
(29%) to carfilzomib; 6 patients (25%) were refractory to both bortezomib and
carfilzomib. In 21 patients evaluable for response, overall response rate (ORR;
>=PR) was 33% (7/21) and 81% (17/21) achieved at least stable disease. Median
progression-free survival (PFS) and overall survival were 3.5 and 9.8 months,
respectively. Significant differences between bortezomib-sensitive and
refractory patients were observed. In bortezomib-sensitive patients, median PFS
was 6.3 months compared to 2.3 months in bortezomib-refractory patients (P <
.001). Median overall survival was not reached vs 4.8 months (P = .046) in
bortezomib-sensitive and bortezomib-refractory patients, respectively. The only
patient refractory to carfilzomib but sensitive to bortezomib achieved very good
partial remission and PFS of 6.3 months, suggesting discrete mechanisms of
resistance to different PIs. As expected, thrombocytopenia and fatigue/asthenia
occurred in nearly all patients (96% and 83%, respectively). Diarrhea was
observed in only 19% of patients which compares favorably with the high rates of
diarrhea reported in the PANORAMA trials. With panobinostat dose reductions in
67% of patients, FVD was tolerated by the majority of patients. In conclusion,
FVD showed efficacy in a heavily pretreated, high-risk multiple myeloma
population with a high degree of patients refractory to novel agents including
PIs.
PMID- 28685864
TI - Rural and Appalachian Disparities in Neonatal Abstinence Syndrome Incidence and
Access to Opioid Abuse Treatment.
AB - OBJECTIVE: Incidence of neonatal abstinence syndrome (NAS) is increasing due to
the rise in opioid use. Rural states like Kentucky have been disproportionally
impacted by opioid abuse, and this study determines NAS burden nationally and in
Kentucky while quantifying differences in access to care between Appalachian and
non-Appalachian counties. METHODS: NAS rates were calculated using National
(2013) and Kentucky (2008-2014) National Inpatient Sample discharge data. Births
were identified using International Classification of Diseases v9 code 779.5 and
live birth codes V30.x-V38.x. Counties were classified as rural, micropolitan, or
metropolitan using census data. Proximity analysis was conducted via mapping from
ZIP code centroid to nearest opioid treatment facility. Distance to treatment
facilities was calculated and then compared using nonparametric testing for
counties by rural and Appalachian status. RESULTS: NAS cases tripled from 2008 to
2014 in Kentucky counties, with a 2013 NAS rate more than double the national NAS
rate. Rural and Appalachian counties experienced an NAS increase per 1,000 births
that was 2-2.5 times higher than urban/non-Appalachian counties, with a greater
number of NAS births overall in Appalachian counties. All opioid treatment
facility types were further from rural patients than micropolitan/metropolitan
patients (P < .001), as well as further for Appalachians versus non-Appalachians
(P < .001, all facility types). CONCLUSIONS: NAS burden disparately affects rural
and Appalachian Kentucky counties, while treatment options are disproportionately
further away for these residents. Policy efforts to increase NAS prevention and
encourage opioid abuse treatment uptake in pregnant women should address rural
and Appalachian disparities.
PMID- 28685865
TI - Development and evaluation of online education to increase the forensic relevance
of oral health records.
AB - BACKGROUND: Human identification can be reliably established by dental
comparison; success is significantly impacted by inadequate ante-mortem
information. Previous Australian research revealed suboptimal recording of
features important for forensic dental identification and compliance with Dental
Board of Australia guidelines. We hence created and evaluated an online education
programme aimed at improving oral health practitioner recording. METHODS: An
interactive learning module (ILM) was constructed and released to three focus
groups representing practitioners with varying experience levels: Australian
Society of Forensic Odontology members, third year dental students and the wider
dental community. Pre- and post-participation perceptions were recorded, with
percentage, mean, broad agreement, standard deviation and statistical
significance between responses determined. RESULTS: Improved recognition of
importance of record keeping, knowledge, confidence, skill and motivation to
learn was seen following ILM interaction. This was particularly significant for
students, participants with 3-5 years of experience in their current occupation
and those whose highest level of education was achieved in Australia.
CONCLUSIONS: The ILM increased self-reported awareness, understanding and
attitude of participants with different levels of case note recording experience;
this can improve recording practises and aid forensic dental identification if
utilized in undergraduate teaching and as a continuing professional development
tool for dental practitioners.
PMID- 28685866
TI - Examining Key Stakeholder and Community Residents' Understanding of Environmental
Influences to Inform Place-Based Interventions to Reduce Obesity in Rural
Communities, Kentucky 2015.
AB - PURPOSE: Rural residents report high rates of obesity, physical inactivity, and
poor eating habits. The objectives of this study were to (1) use the collective
impact model to guide efforts to elicit community members' perceptions of county
specific factors influencing high obesity rates; (2) determine the association
between utilization of food retail venues and concern about obesity and healthy
eating; and (3) determine community members' utilization of physical activity
infrastructure and concern about physical inactivity. METHODS: The study was
conducted in 6 rural counties in Kentucky with adult obesity prevalence rates
>40%. Community stakeholders met to assess counties' needs and assets in
implementing interventions to reduce obesity in their communities. A random-digit
dial survey (n = 756) also was conducted to examine awareness and availability of
community resources for healthy eating and physical activity. FINDINGS:
Stakeholders identified lack of access to fruits and vegetables and poor physical
activity infrastructure as contributors to obesity. Reporting moderate and
serious concern about obesity and healthy eating was associated with higher odds
of shopping at a supercenter compared with those expressing little concern.
Reported access to information about physical activity opportunities was
associated with higher odds of reporting the availability of safe places for
physical activity, sidewalks, and trails compared with those who reported that
information was difficult to obtain. CONCLUSIONS: This study elicits community
identified barriers to healthy behaviors and provides foundational data to inform
future place-based obesity reduction interventions.
PMID- 28685867
TI - MiR-150 alleviates neuropathic pain via inhibiting toll-like receptor 5.
AB - MicroRNAs (miRNAs) are reported as vital participators in the pathophysiological
course of neuropathic pain. However, the underlying mechanisms of the functional
roles of miRNAs in neuropathic pain are largely unknown. This study was designed
to explore the potential role of miR-150 in regulating the process of neuropathic
pain in a rat model established by chronic sciatic nerve injury (CCI).
Overexpression of miR-150 greatly alleviated neuropathic pain development and
reduced inflammatory cytokine expression, including COX-2, interleukin IL-6, and
tumor necrosis factor (TNF)-alpha in CCI rats. By bioinformatic analysis, 3'
untranslated region (UTR) of Toll-like receptor (TLR5) was predicted to be a
target of miR-150. TLR5 commonly serves as an important regulator of
inflammation. Overexpression of miR-150 significantly suppressed the expression
of TLR5 in vitro and in vivo. Furthermore, upregulation of TLR5 decreased the miR
150 expression and downregulation of TLR5 increased miR-150, respectively.
Overexpression of TLR5 significantly reversed the miR-150-induced suppressive
effects on neuropathic pain. In conclusion, our current study indicates that miR
150 may inhibit neuropathic pain development of CCI rats through inhibiting TLR5
mediated neuroinflammation. Our findings suggest that miR-150 may provide a novel
therapeutic target for neuropathic pain treatment.
PMID- 28685868
TI - Body size evolution in an old insect order: No evidence for Cope's Rule in spite
of fitness benefits of large size.
AB - We integrate field data and phylogenetic comparative analyses to investigate
causes of body size evolution and stasis in an old insect order: odonates
("dragonflies and damselflies"). Fossil evidence for "Cope's Rule" in odonates is
weak or nonexistent since the last major extinction event 65 million years ago,
yet selection studies show consistent positive selection for increased body size
among adults. In particular, we find that large males in natural populations of
the banded demoiselle (Calopteryx splendens) over several generations have
consistent fitness benefits both in terms of survival and mating success.
Additionally, there was no evidence for stabilizing or conflicting selection
between fitness components within the adult life-stage. This lack of stabilizing
selection during the adult life-stage was independently supported by a literature
survey on different male and female fitness components from several odonate
species. We did detect several significant body size shifts among extant taxa
using comparative methods and a large new molecular phylogeny for odonates. We
suggest that the lack of Cope's rule in odonates results from conflicting
selection between fitness advantages of large adult size and costs of long larval
development. We also discuss competing explanations for body size stasis in this
insect group.
PMID- 28685869
TI - Biomarkers of the alcohol hangover state: Ethyl glucuronide (EtG) and ethyl
sulfate (EtS).
AB - INTRODUCTION: The aim of this study was to investigate the usefulness of ethyl
glucuronide (EtG) and ethyl sulfate (EtS) as biomarkers of the hangover state.
METHODS: Thirty-sixhealthy social drinkers participated in this study, being of
naturalistic design. Eighteen participants experience regular hangovers (the
hangover group), whereas the other 18 claim to not experience a hangover (the
hangover-immune group). On a control day (alcohol-free) day and a post-alcohol
day, urine EtG and EtS concentrations were determined and hangover severity
assessed. RESULTS: Urinary EtG and EtS concentrations were significantly
increased on post-alcohol day compared to the control day (p = .0001). Both EtG
and EtS concentrations did not significantly correlate with the overall hangover
score, nor with the estimated peak blood alcohol concentrations and number of
alcoholic drinks. EtG correlated significantly only with the individual hangover
symptom "headache" (p = .033; r = .403). No significant correlations were found
with the EtG to EtS ratio. EtG and EtS concentrations significantly correlated
with urine ethanol concentrations. CONCLUSIONS: Although urine EtG and EtS
concentration did not significantly correlate to estimated peak blood alcohol
concentrations or the number of alcoholic drinks consumed, a significant
correlation was found with urine ethanol concentration. However, urine EtG and
EtS concentrations did not significantly correlate with overall hangover
severity.
PMID- 28685870
TI - Novel echocardiographic prognostic markers for cardiac tamponade in patients with
large malignant pericardial effusions: A paradigm shift from flow to tissue
imaging.
AB - BACKGROUND: With this study, we sought to investigate the prognostic value of
echocardiographic tissue imaging markers in predicting tamponade among patients
with large malignant pericardial effusion compared to routinely used
echocardiographic signs. METHODS: A total of 96 consecutive patients with large
malignant pericardial effusion, not in clinical cardiac tamponade, underwent an
echocardiographic examination and were prospectively assessed for 1 month.
Clinically evident cardiac tamponade was considered as the study endpoint. The
prognostic performance of tricuspid valve annular plane systolic excursion
(TAPSE) and peak systolic annular velocity at the lateral margin of the tricuspid
valve annulus (STV ) was assessed and compared to routinely used imaging signs.
RESULTS: During follow-up, 37 patients (39%) developed clinically evident cardiac
tamponade. TAPSE (area under the curve [AUC] 0.958) and STV (AUC 0.948) had
excellent predictive accuracy for tamponade. Multivariate analysis showed that
TAPSE (Hazard ratio [HR] 3.03; 95% CI 1.60-5.73, P=.001) and STV (HR 1.17; 95% CI
1.05-1.29, P=.005) remained independent significant predictors of cardiac
tamponade. Reclassification analysis and decision curve analysis showed additive
prognostic value and adjunct clinical benefit of these markers when added to a
recently published triage pericardiocentesis score. CONCLUSION: Echocardiographic
tissue imaging markers such as TAPSE and STV are characterized by an excellent
prognostic ability for development of cardiac tamponade and better prognostic
value compared to routine echocardiographic signs in patients with large
malignant pericardial effusion. Incorporating these markers to a recent triage
pericardiocentesis score resulted in additional prognostic value and increased
clinical benefit.
PMID- 28685871
TI - Ensuring Community Participation During Program Planning: Lessons Learned During
the Development of a HIV/STI Program for Young Sexual and Gender Minorities.
AB - HIV/STI incidence has shifted to a younger demographic, comprised
disproportionately of gay and bisexual men, transgender women, and people of
color. Recognizing the importance of community organizing and participatory
engagement during the intervention planning process, we describe the steps taken
to engage diverse constituents (e.g., youth and practitioners) during the
development of a structural-level HIV/STI prevention and care initiative for
young sexual and gender minorities in Southeast Michigan. Our multi-sector
coalition (MFierce; Michigan Forward in Enhancing Research and Community Equity)
utilized a series of community dialogues to identify, refine, and select
programmatic strategies with the greatest potential. Evaluation data (N = 173)
from the community dialogues highlighted constituents' overall satisfaction with
our elicitation process. Using a case study format, we describe our community
dialogue approach, illustrate how these dialogues strengthened our program
development, and provide recommendations that may be used in future community
based program planning efforts.
PMID- 28685872
TI - Synthesis and Characterization of Bioinspired [Mo2 Fe2 ]-Hydride Cluster
Complexes and Their Application in the Catalytic Silylation of N2.
AB - The hydride-supported [Mo2 Fe2 ] cluster complex {Cp*Mo(PMe3 )}2 {FeN(SiMe3 )2 }2
(H)8 (2 a; Cp*=eta5 -C5 Me5 ) and its [Mo2 Mn2 ] congener 2 b were synthesized
from the reactions of Cp*Mo(PMe3 )(H)5 (1) with M{N(SiMe3 )2 }2 (M=Fe, Mn). The
amide-to-thiolate ligand-exchange reactions of complex 2 a with bulky thiol
reagents (HSR; R=2,4,6-iPr3 C6 H2 (Tip), 2,6-(SiMe3 )2 C6 H3 (Btp)) furnished the
corresponding hydride-supported [Mo2 Fe2 ](SR)2 cluster complexes. The [Mo2 Fe2 ]
clusters served as catalyst precursors for the reductive silylation of N2 and
yielded ~65-69 equivalents of N(SiMe3 )3 relative to the [Mo2 Fe2 ] clusters.
Treatment of complexes 2 a and b with an excess of CNtBu resulted in the
formation of dinuclear Mo-Fe and Mo-Mn complexes, which indicated that the [Mo2
M2 ] cores (M=Fe, Mn) split into two dinuclear species upon accommodation of
substrates.
PMID- 28685873
TI - Three cases of Klinefelter's syndrome with unilateral absence of vas deferens.
AB - Genital abnormalities such as congenital uni/bilateral absence of the vas
deferens are very rare in Klinefelter's syndrome. Here, we report three cases of
Klinefelter's syndrome with unilateral absence of the vas deferens. All cases had
small testicles, and unilateral vas deferentia were not palpable. Hormonal
evaluations revealed hypergonadotropism. One case had elevated prolactin level,
and pituitary adenoma was detected by magnetic resonance imaging. All cases were
diagnosed as Klinefelter's syndrome (one of them had mosaicism) cytogenetically,
and some CFTR gene mutations were detected. To our knowledge, this is the first
case series of both conditions existing simultaneously.
PMID- 28685875
TI - Utilizing Palladium-Stabilized Zwitterions for the Construction of N
Heterocycles.
AB - Pd catalysis provides a convenient method for the generation of zwitterionic
intermediates that offer significant opportunities for the synthesis of
functionalized heterocycles. The combination of electrophilic pi-allyl Pd
fragments and C-, N- and O-centered nucleophiles allows these intermediates to
react with readily available substrates to furnish a range of high value products
with control of chemo-, regio- and stereo-selectivity.
PMID- 28685874
TI - Prediction of contrast-induced acute kidney injury by early post-procedural
analysis of urinary biomarkers and intra-renal Doppler flow indices in patients
undergoing coronary angiography.
AB - BACKGROUND: The study was designed to evaluate the applicability of combined
assessment of urinary biomarkers and intra-renal Doppler flow indices for the
prediction of contrast-induced acute kidney injury (CI-AKI) after coronary
angiography/percutaneous coronary interventions (CA/PCI). METHODS: This
prospective observational study covered 95 consecutive patients with coronary
artery disease subject to elective or urgent CA/PCI. Doppler intra-renal flow
indices were assessed before and 1 h following CA/PCI. Urine samples were
collected within 24 h before and 6 h after CA/PCI and assayed for urinary
interleukin-18 (IL-18), liver-fatty acid-binding protein (L-FABP), and kidney
injury molecule-1 (KIM-1) using ELISA method. CI-AKI was defined as >=50%
relative or >=0.3 mg/dL absolute increase of serum creatinine concentration at 48
h post-procedurally. RESULTS: CI-AKI was confirmed in nine patients (9.5%). CI
AKI onset was associated with significantly higher urinary KIM-1 at 6 h (P =
0.003) and DeltaKIM-1 concentrations (P = 0.001), and urinary IL-18 at 6 h (P =
0.014) and DeltaIL-18 concentrations (P = 0.012), however, L-FABP and DeltaL-FABP
levels were comparable in both groups. Receiver operating characteristic curve
analysis denoted that post-procedural IL-18 levels at 6 h >89.8 pg/mg (AUC =
0.75, P = 0.007), KIM-1 at 6 h >0.425 ng/mg (AUC = 0.81, P = 0.001), renal
resistive index (RRI) at 1 h >0.73 (AUC 0.88; P < 0.0001), and renal pulsatility
index (RPI) at 1 h >0.86 (AUC = 0.86; P < 0.0001) predicted CI-AKI onset.
Logistic regression analysis of postoperative predictors revealed that IL-18 and
RRI were independent predictors of CI-AKI onset (AUC = 0.96; P < 0.0001).
CONCLUSIONS: Joint assessment of early post-procedural urinary biomarkers and
Doppler renovascular parameters aids early diagnosis of CI-AKI in patients
undergoing coronary interventions.
PMID- 28685876
TI - EUS-FNA of the Merkel cell carcinoma metastasis to the pancreas: Cytomorphology
and immunocytochemistry on direct cytological smears.
AB - OBJECTIVE: To report two cases of Merkel cell carcinoma (MCC) metastatic to the
pancreas diagnosed with endoscopic ultrasound-guided-fine needle aspiration (EUS
FNA) and to add the case of concomitant chronic lymphocytic leukaemia/small
lymphocytic lymphoma (CLL/SLL) and MCC to the literature. The aim is to alert the
cytopathologists once more to the problems of differential diagnosis of
pancreatic metastasis of MCC and to describe the possibilities of ancillary
methods performed on direct cytological smears. METHODS: EUS-FNA procedures were
performed according to standard institution protocol, using 22-G needles with
cytopathologist on-site. Based on rapid on-site evaluation (ROSE), additional
passes were made for immunocytochemistry (ICC). A mini panel of antibodies was
used to aid the differential diagnosis. RESULTS: Smears revealed a dispersed
pattern of small round cells with scant cytoplasm, round nuclei with
inconspicuous nucleoli and occasional nuclear moulding, suspicious of small cell
carcinoma. Results of ICC applied to the direct cytological smears were as
follows: LCA negative, Cytokeratin (clone MNF116) positive, TTF-1 negative, CD 56
positive, NSE weakly positive, Chromogranin A weakly positive and CK20 positive,
in one case in a dot-like perinuclear pattern. The diagnosis of MCC was made.
CONCLUSION: Increasing incidence of MCC warrants the inclusion of MCC in the
differential diagnosis of tumours of small round blue cell morphology even in
unusual sites. The cytomorphological features coupled with an ICC panel are
usually enough to make a confident diagnosis of MCC. EUS-FNA is a minimally
invasive technique which enables sampling adequate tissue for all the ancillary
methods eventually needed to support the diagnosis.
PMID- 28685877
TI - Availability of immunocytochemistry using cocktail antibody targeting
p63/cytokeratin14 for the differential diagnosis of fibroadenoma and ductal
carcinoma in situ in fine needle aspiration cytology of the breast.
AB - OBJECTIVE: The differential diagnosis of fibroadenoma (FA) and ductal carcinoma
in situ (DCIS) has been problematic in fine needle aspiration biopsy (FNAC)
because it has been difficult to differentiate between the "large epithelial
clusters" associated with FA and those associated with DCIS. The purpose of this
study was to prospectively validate the usefulness of immunocytochemical staining
using cocktail antibody targeting p63/CK14 in the differential diagnosis of FA
and DCIS. MATERIALS AND METHODS: Twenty patients diagnosed as having an uncertain
malignant potential (indeterminate) for breast cancer on the basis of a FNAC
finding were selected randomly: ten patients with FA and ten with DCIS. The cover
glass on a specimen stained with the Papanicolaou stain on a glass slide was
peeled off, and the specimen was restained by immunocytochemical staining of
cocktail antibody targeting p63 and CK14. RESULTS: Six of the twenty patients
were CK14-immunopositive: FA, 6; DCIS, 0. The remaining patients were CK14
immunonegative: FA, 4; DCIS, 10. The number of CK14-immunopositive DCIS patients
was significantly different from that of FA patients (P=.0054). Eight out of the
twenty patients were p63-immunopositive: FA, 8; DCIS, 0. The remaining patients
were p63-immunonegative: FA, 2; DCIS, 10. The number of p63-immunopositive DCIS
patients was significantly different from that of FA patients (P=.0004).
CONCLUSIONS: Immunocytochemical staining using cocktail antibody targeting
p63/CK14 was useful for the differential diagnosis of FA and DCIS in FNAC of the
breast.
PMID- 28685878
TI - Few Atomic Layered Lithium Cathode Materials to Achieve Ultrahigh Rate Capability
in Lithium-Ion Batteries.
AB - The most promising cathode materials, including LiCoO2 (layered), LiMn2 O4
(spinel), and LiFePO4 (olivine), have been the focus of intense research to
develop rechargeable lithium-ion batteries (LIBs) for portable electronic
devices. Sluggish lithium diffusion, however, and unsatisfactory long-term
cycling performance still limit the development of present LIBs for several
applications, such as plug-in/hybrid electric vehicles. Motivated by the success
of graphene and novel 2D materials with unique physical and chemical properties,
herein, a simple shear-assisted mechanical exfoliation method to synthesize few
layered nanosheets of LiCoO2 , LiMn2 O4 , and LiFePO4 is used. Importantly, these
as-prepared nanosheets with preferred orientations and optimized stable
structures exhibit excellent C-rate capability and long-term cycling performance
with much reduced volume expansion during cycling. In particular, the zero-strain
insertion phenomenon could be achieved in 2-3 such layers of LiCoO2 electrode
materials, which could open up a new way to the further development of next
generation long-life and high-rate batteries.
PMID- 28685879
TI - AgGa2 PS6 : A New Mid-Infrared Nonlinear Optical Material with a High Laser
Damage Threshold and a Large Second Harmonic Generation Response.
AB - To develop new mid-infrared (MIR) nonlinear optical (NLO) materials, which can
overcome the low laser damage threshold (LDT) of the commercial MIR-NLO crystals
(AgGaS2 , AgGaSe2 and ZnGeP2 ) and simultaneously keep the large NLO
susceptibility, is necessary for high-power MIR laser frequency conversion
technology. To improve the LDT, a new strategy of increasing lattice stability
was adopted. Here, the strongly covalent structural unit of the PS4 tetrahedron
was introduced into AgGaS2 (AGS), and that led to the isolation of the first
compound in AgI -GaIII -PV -S system, namely, AgGa2 PS6 (Cc). It retains a large
SHG efficiency (1.0*AGS) with phase-matchable ability, and also exhibits an
improved LDT (5.1*AGS), indicating AgGa2 PS6 is a new promising MIR-NLO crystal.
Moreover, a novel 3D framework of [Ga2 PS6 ]- , with triangular-shaped channels,
as well as interesting single triangular geometry of AgS3 -both of which are very
rare in reported sulfides-was discovered in AgGa2 PS6 . Furthermore, theoretical
calculations, and lattice energy and thermal expansions analyses suggest that the
PS4 group makes a large contribution to the large SHG efficiency and high LDT.
PMID- 28685880
TI - Palladium on Carbon-Catalyzed Benzylic Methoxylation for Synthesis of Mixed
Acetals and Orthoesters.
AB - The palladium on carbon (Pd/C)-catalyzed direct methoxylation of the benzylic
positions of linear benzyl and cyclic ether substrates proceeded in the presence
of i-Pr2 NEt under an oxygen atmosphere to give the corresponding mixed acetals.
Cyclic acetal derivatives could also be converted into orthoesters. The present
direct methoxylation via a carbon-hydrogen (C-H) functionalization can be
accomplished using the easily-removed Pd/C and molecular oxygen as a green
oxidant. The obtained mixed acetals were transformed into the corresponding ether
products by chemoselective substitution of the methoxy group using a
silyltriflate, 2,4,6-collidine, and a nucleophile. The orthoester derivative
could also be transformed into the cyclic ketal under similar reaction
conditions.
PMID- 28685881
TI - Central metabolite and sterol profiling divides tobacco male gametophyte
development and pollen tube growth into eight metabolic phases.
AB - While changes in the transcriptome and proteome of developing pollen have been
investigated in tobacco and other species, the metabolic consequences remain
rather unclear. Here, a broad range of metabolites was investigated in close
succession of developmental stages. Thirteen stages of tobacco male gametophyte
development were collected, ranging from tetrads to pollen tubes. Subsequently,
the central metabolome and sterol composition were analyzed by GC-mass
spectrometry (MS), monitoring 77 metabolites and 29 non-identified analytes. The
overall results showed that development and tube growth could be divided into
eight metabolic phases with the phase including mitosis I being most distinct.
During maturation, compounds such as sucrose and proline accumulated. These were
degraded after rehydration, while gamma-aminobutyrate transiently increased,
possibly deriving from proline breakdown. Sterol analysis revealed that tetrads
harbor similar sterols as leaves, but throughout maturation unusual sterols
increased. Lastly, two further sterols exclusively accumulated in pollen tubes.
This study allows a deeper look into metabolic changes during the development of
a quasi-single cell type. Metabolites accumulating during maturation might
accelerate pollen germination and tube growth, protect from desiccation, and feed
pollinators. Future studies of the underlying processes orchestrating the changes
in metabolite levels might give valuable insights into cellular regulation of
plant metabolism.
PMID- 28685882
TI - Simultaneous patch testing with fragrance mix I, fragrance mix II and their
ingredients in southern Sweden between 2009 and 2015.
AB - BACKGROUND: Fragrance mix I (FM I) and fragrance mix II (FM II) are included in
the European baseline series as screening substances for fragrance contact
allergy. OBJECTIVES: To investigate the frequency of allergic reactions to FM I,
FM II and their ingredients in consecutively patch tested patients. MATERIALS AND
METHODS: A retrospective analysis of data from 4430 patients patch tested between
2009 and 2015 was performed. RESULTS: Of the patients, 6.5% were FM I-positive
and 3.2% were FM II-positive. Forty-five per cent of FM I-positive patients did
not have positive reactions to FM I ingredients. Thirty-five per cent of those
who were FM II-positive did not have positive reactions to FM II ingredients.
Twenty-seven per cent of those with positive reactions to one or more of the FM I
ingredients were FM I-negative, and 36% of those who had positive reactions to
one or more of the FM II ingredients were FM II-negative. The allergens with the
highest pick-up rates were Evernia prunastri (1.8%), cinnamal (1.3%), citral
(1.2%), and hydroxyisohexyl 3-cyclohexene carboxaldehyde (1.2%). Significant
differences were observed in the proportions of positive reactions to FM I, FM
II, eugenol, isoeugenol, and farnesol when results from patch testing with
materials from different suppliers were compared. CONCLUSIONS: There is a risk of
missing fragrance contact allergy when testing with only the fragrance mixes is
performed. The use of preparations from different suppliers may affect the patch
test results.
PMID- 28685883
TI - Intra- and inter-observer reproducibility of CINtec(r) PLUS in ThinPrep(r)
cytology preparations.
AB - BACKGROUND: This study evaluated the intra- and inter-observer reproducibility of
the dual-stain biomarker, CINtec(r) PLUS cytology in ThinPrep(r) specimens, for
improved specificity in the detection of cervical disease in women testing human
papillomavirus (HPV) positive. METHODS: A total of 972 cases of HPV-positive
women from a triage and primary HPV screening population were selected from an
ongoing study evaluating the clinical performance of CINtec(r) PLUS cytology. For
reproducibility analyses, three cytotechnologists rescreened sets of slides which
they had previously reported themselves and which were previously reported by
each of the other cytotechnologists. The original results of slides previously
screened by each of the three cytotechnologists were also compared with the
results of an expert reference evaluator. RESULTS: Intra- and inter-observer
agreement for paired evaluations between reviewers ranged from 82.8% to 94.9%
(kappa 0.65-0.91) and 89.2% to 93% (kappa 0.83-0.88), respectively.
Reproducibility analyses between the cytotechnologists and the reference
evaluator revealed agreements ranging from 95.5% to 98% (kappa 0.89-0.96).
CONCLUSION: Evaluation of the dual-stain biomarker showed a high level of
agreement across all evaluators suggesting that CINtec(r) PLUS cytology will
perform well in the hands of cytotechnologists and pathologist reviewers and
could be introduced into cellular pathology laboratories that employ ThinPrep(r)
LBC with a minimum effort.
PMID- 28685884
TI - Correlates of Injection Drug Use Among Rural Appalachian Women.
AB - BACKGROUND: Limited research has focused on correlates of injection drug use
(IDU) among high-risk subgroups of drug users, particularly women, who may be at
increased risk for transmission of infectious diseases such as HIV and Hepatitis
C. The purpose of this study is to better understand the contextual and health
correlates of IDU among women living in rural Appalachia by examining (1)
differences between injectors and noninjectors, and (2) the unique correlates of
recent IDU and past IDU. METHODS: This study involved random selection,
screening, and face-to-face interviews with 400 rural Appalachian women from
jails in one state. Analyses included descriptive statistics, multinomial
logistic regression, and stepwise regression to identify significant correlates
of recent IDU and past IDU compared to never injecting. RESULTS: Findings
indicated that 75.3% of this randomly selected sample reported lifetime injection
of drugs. Contextual factors including drug use severity (RRR = 8.66, P < .001),
more male sex partners (RRR = 1.01, P < .05), and having injecting partners (RRR
= 7.60, P < .001) were robust correlates of recent injection practices.
CONCLUSIONS: This study makes an important contribution to understanding factors
associated with IDU among rural Appalachian women drug users, which are strongly
associated with both relational and health factors. Study findings on the
specific factors associated with IDU risk have important implications for
tailoring and targeting interventions that should include a focus on the
relationship context reducing high-risk injection practices.
PMID- 28685885
TI - Mental Health and Substance Use Care Among Young Adults Before and After
Affordable Care Act (ACA) Implementation: A Rural and Urban Comparison.
AB - PURPOSE: Rural young adults experience greater unmet need for mental health (MH)
and alcohol or drug (AOD) treatment and lower health insurance coverage than
urban residents. It is unknown whether Affordable Care Act (ACA) reforms in 2010
(dependent coverage extended to age 26) or 2014 (Medicaid expansion) closed
rural/urban gaps in insurance and treatment. The present study compared changes
in rates of health insurance, MH treatment, and AOD treatment for rural and urban
young adults over a period of ACA reforms. METHODS: Young adult participants (18
25 years) in the National Survey on Drug Use and Health (2008-2014) with past
year psychological distress or AOD abuse were included. Difference-in-differences
logistic regression models estimated rural/urban differences in insurance, MH,
and AOD treatment pre- versus post-ACA reforms. Analyses adjusted for gender,
race, marital status, and health status. RESULTS: Among 39,482 young adults with
psychological distress or AOD, adjusted insurance rates increased from 72.0% to
81.9% (2008-2014), but a significant rural/urban difference (5.1%) remained in
2014 (P < .05). Among young adults with psychological distress (n = 23,470), MH
treatment rates increased following 2010 reforms from 30.2% to 33.0%, but gains
did not continue through 2014. Differences in MH treatment over time did not vary
by rural/urban status and there were no significant changes in AOD treatment for
either group. CONCLUSIONS: Although rates of insurance increased for all young
adults, a significant rural/urban difference persisted in 2014. Meaningful
increases in MH and AOD treatment may require targeted efforts to reduce
noninsurance barriers to treatment.
PMID- 28685886
TI - Longitudinal Adaptations of Bone Mass, Geometry, and Metabolism in Adolescent
Male Athletes: The PRO-BONE Study.
AB - Adolescence is a crucial period for bone development, and exercise can enhance
bone acquisition during this period of life. However, it is not known how the
different loading sports practiced can affect bone acquisition in adolescent male
athletes. Therefore, the purpose of the present study was to determine the 1-year
longitudinal bone acquisition among adolescent males involved in osteogenic
(football) and non-osteogenic (swimming and cycling) sports and to compare with
active controls. A total of 116 adolescent males aged 12 to 14 years at baseline
were followed for 1 year: 37 swimmers, 37 footballers, 28 cyclists, and 14 active
controls. Bone mineral content (BMC) was assessed using dual-energy X-ray
absorptiometry (DXA); cross-sectional area (CSA), cross-sectional moment of
inertia (CSMI), and section modulus (Z) at the femoral neck was assessed using
hip structural analysis (HSA); and bone texture of the lumbar spine was assessed
using trabecular bone score (TBS). Serum N-terminal propeptide of procollagen
type I (PINP), isomer of the Carboxi-terminal telopeptide of type 1 collagen (CTX
I), total serum calcium, and 25 hydroxyvitamin D [25(OH)D] were analyzed.
Footballers had significantly higher adjusted BMC at the lumbar spine (7.0%) and
femoral neck (5.0%) compared with cyclists, and significantly greater BMC at the
lumbar spine (6.9%) compared with swimmers. Footballers presented significantly
greater TBS (4.3%) compared with swimmers, and greater CSMI (10.2%), CSA (7.1%),
Z (8.9%) and TBS (4.2%) compared with cyclists. No differences were noted between
cyclists and swimmers, both groups had similar bone acquisition compared with
controls. PINP was significantly higher in footballers and controls compared with
cyclists and swimmers (3.3% to 6.0%), and 25(OH)D was significantly higher in
footballers and cyclists compared with swimmers and controls (9.9% to 13.1%).
These findings suggest that bone acquisition is higher in adolescent male
footballers compared with swimmers and cyclists at the femoral neck and lumbar
spine sites of the skeleton. (c) 2017 American Society for Bone and Mineral
Research.
PMID- 28685887
TI - The first cases of Candida auris candidaemia in Oman.
AB - Candida auris has been recognised as a problematic healthcare-associated emerging
yeast which is often misidentified as Candida haemulonii by commercial systems.
Correct early identification of C. auris is important for appropriate antifungal
treatment and implementing effective infection control measures. Here we report
emergence of the first C. auris cases in Oman, initially misidentified as C.
haemulonii.
PMID- 28685888
TI - Address-Based Sampling for Recruiting Rural Subpopulations: A 2-Phase, Multimode
Approach.
AB - PURPOSE: This article describes recruitment of a subpopulation of women in a
rural area, extending an existing method of a 2-phase address-based sampling
protocol to include a mixed-mode approach. METHODS: Phase 1 included a household
enumeration questionnaire mailed to randomly selected households (n = 1,950) in 3
Ohio Appalachian counties to identify members of the eligible subgroup. The
second phase of recruitment involved contacting 1 randomly selected eligible
woman enumerated by each household, based on return of the questionnaire. These
women (n = 599) were invited by field interviewers to participate in a one-time
in-person health survey. FINDINGS: Of the women invited to participate, a total
of 408 completed the interview. Based on American Association for Public Opinion
Research Response Rate 1 calculations, the response rates were 44.4% and 70.3%
for phases 1 and 2, respectively. Response rates in this study were encouraging,
especially for the second phase in-person interview. CONCLUSION: We discuss
implications for future research using a mixed-mode approach in this
subpopulation.
PMID- 28685889
TI - Correlates of Community-Based Colorectal Cancer Screening in a Rural Population:
The Role of Fatalism.
AB - OBJECTIVE: One largely unexplored barrier to colorectal cancer (CRC) screening is
fatalistic beliefs about cancer. The purpose of this study was to identify
correlates of ever having endoscopy screenings for CRC and to determine whether
fatalism plays a unique role. Because evidence suggests that cancer-associated
fatalistic beliefs may be particularly common among rural Americans, the study
was conducted in a medically underserved area of rural Appalachia. METHODS:
Rural residents (N = 260) between 51 and 75 years of age, from a medically
underserved area of Appalachia, Kentucky, were recruited for a cross-sectional
study. The outcome measure was assessed by a single item asking whether
participants ever had a colonoscopy or flexible sigmoidoscopy. Demographic and
health-related correlates of this outcome were selected based on past studies of
rural populations. A single item assessed perceptions of fatalism regarding CRC.
Age-adjusted analyses of correlates testing significant at the bivariate level
were conducted. RESULTS: The analytic sample was limited to 135 rural residents
indicating they had ever had CRC endoscopy and 107 indicating never having
endoscopy. In age-adjusted analyses, only the measure of fatalism had a
significant association with having endoscopy. Those endorsing the statement
pertaining to fatalism were 2.3 times more likely (95% CI = 1.24-4.27, P = .008)
than the remainder to indicate never having endoscopy. CONCLUSIONS: A community
based approach to the promotion of endoscopy for CRC screening could focus on
overcoming CRC-associated fatalism, thereby potentially bringing more unscreened
people to endoscopy clinics.
PMID- 28685890
TI - Impact of the phased abolition of co-payments on the utilisation of selected
prescription medicines in Wales.
AB - We have taken advantage of a natural experiment to measure the impact of the
phased abolition of prescription co-payments in Wales. We investigated 3 study
periods covering the phased abolition: from L6 to L4, L4 to L3, and L3 to L0. A
difference-in-difference modelling was adopted and applied to monthly UK general
practice level dispensing data on 14 selected medicines which had the highest
percentage of items dispensed subject to a co-payment prior to abolition.
Dispensing from a comparator region (North East of England) with similar health
and socio-economic characteristics to Wales, and where prescription co-payments
continued during the study periods, was used to isolate any non-price effects on
dispensing in Wales. Results show a small increase in dispensing of 14 selected
medicines versus the comparator. Compared with NE England, monthly average Welsh
dispensing was increased by 11.93 items (7.67%; 95% CI [7.2%, 8.1%]), 6.37 items
(3.38%; 95% CI [2.9%, 3.7%]) and 9.18 items (4.54%; 95% CI [4.2%, 4.9%]) per
practice per 1,000 population during the periods when co-payment was reduced.
Price elasticities of the selected medicines utilisation were -0.23, -0.13, and
0.04 in 3 analyses, suggesting the abolition of co-payment had small effect on
Welsh dispensing.
PMID- 28685891
TI - Specification of neurotransmitter identity by Tal1 in thalamic nuclei.
AB - BACKGROUND: The neurons contributing to thalamic nuclei are derived from at least
two distinct progenitor domains: the caudal (cTH) and rostral (rTH) populations
of thalamic progenitors. These neural compartments exhibit unique neurogenic
patterns, and the molecular mechanisms underlying the acquisition of
neurotransmitter identity remain largely unclear. RESULTS: T-cell acute
lymphocytic leukemia protein 1 (Tal1) was expressed in the early postmitotic
cells in the rTH domain, and its expression was maintained in mature thalamic
neurons in the ventrolateral geniculate nucleus (vLG) and the intergeniculate
leaflet (IGL). To investigate a role of Tal1 in thalamic development, we used a
newly generated mouse line driving Cre-mediated recombination in the rTH domain.
Conditional deletion of Tal1 did not alter regional patterning in the developing
diencephalon. However, in the absence of Tal1, rTH-derived thalamic neurons
failed to maintain their postmitotic neuronal features, including
neurotransmitter profile. Tal1-deficient thalamic neurons lost their GABAergic
markers such as Gad1, Npy, and Penk in IGL/vLG. These defects may be associated
at least in part with down-regulation of Nkx2.2, which is known as a critical
regulator of rTH-derived GABAergic neurons. CONCLUSIONS: Our results demonstrate
that Tal1 plays an essential role in regulating neurotransmitter phenotype in the
developing thalamic nuclei. Developmental Dynamics 246:749-758, 2017. (c) 2017
Wiley Periodicals, Inc.
PMID- 28685892
TI - Randomized controlled trial of a peer led multimodal intervention for men with
prostate cancer to increase exercise participation.
AB - OBJECTIVE: Exercise may reduce morbidity, increase survival, and improve quality
of life (QoL) in prostate cancer patients. However, effective ways to encourage
exercise outside carefully controlled clinical trials remain uncertain. We
evaluated the effectiveness of peer-led self-management for increasing exercise
participation in men with localized prostate cancer. METHODS: Four hundred and
sixty-three prostate cancer patients from Queensland, Australia were randomized
to a monthly telephone-based group peer support for 6 months supported by self
management materials and exercise equipment (INT, n = 232) or usual care (UC, n =
231). Participants were assessed at baseline, 3, 6, and 12 months. Primary
outcomes were compliance with exercise guidelines; secondary outcomes were
psychological distress and QoL. RESULTS: Patients in INT engaged in more
resistance exercise than UC at 3 months (19.4 [95% CI 6.52 to 32.28] min/wk, P =
.003) and 6 months (14.6 [95% CI 1.69 to 27.58] min/wk, P = .027); more men
achieved sufficient physical activity levels at 3 months (chi2 = 8.89, P =
0.003). There was no difference between groups for aerobic-based activity at any
time point nor for resistance exercise time at 12-month follow-up. INT had higher
QoL Relationships scores at 3 months (.03 [95% CI .00 to .06], P = .038) compared
with UC. Limitation included self-reported assessment of exercise. CONCLUSIONS:
Peer-led intervention was effective in increasing patients' resistance exercise
participation in the short-to-medium term and in the number of men achieving
sufficient activity levels in the short-term; however, this was not accompanied
by overall improvements in QoL or psychological distress. Methods to increase
effectiveness and maintain long-term adherence require further investigation.
PMID- 28685893
TI - Alterations in white matter microstructure are associated with goal-directed
upper-limb movement segmentation in children born extremely preterm.
AB - Altered white matter microstructure is commonly found in children born preterm
(PT), especially those born at an extremely low gestational age (GA). These
children also commonly show disturbed motor function. This study explores the
relation between white matter alterations and upper-limb movement segmentation in
41 children born PT (19 girls), and 41 children born at term (18 girls) at 8
years. The PT group was subdivided into extremely PT (E-PT; GA = 25-27 weeks, N =
10), very PT (V-PT; GA = 28-32 weeks, N = 13), and moderately PT (M-PT; GA = 33
35 weeks, N = 18). Arm/hand preference (preferred/non-preferred) was determined
through object interactions and the brain hemispheres were designated
accordingly. White matter alterations were assessed using diffusion tensor
imaging in nine areas, and movement segmentation of the body-parts head,
shoulder, elbow, and wrist were registered during a unimanual goal-directed task.
Increased movement segmentation was demonstrated consistently on the preferred
side in the E-PT group compared with the term born group. Also compared with the
term born peers, the E-PT group demonstrated reduced fractional anisotropy (FA)
in the cerebral peduncle (targeting the corticospinal tract) in the hemisphere on
the non-preferred side and in the splenium of corpus callosum. In contrast, in
the anterior internal capsule on the preferred side, the E-PT group had increased
FA. Lower FA in the cerebral peduncle, but higher FA in the anterior internal
capsule, was associated with increased movement segmentation across body-parts in
a contralateral manner. The results suggest that impaired development of
sensorimotor tracts in E-PT children could explain a sub-optimal spatiotemporal
organization of upper-limb movements. Hum Brain Mapp 38:5051-5068, 2017. (c) 2017
Wiley Periodicals, Inc.
PMID- 28685894
TI - Digest: Using transcriptomics to map parental care behavior in burying beetles.
PMID- 28685895
TI - Restoration of microRNA-708 sensitizes ovarian cancer cells to cisplatin via
IGF2BP1/Akt pathway.
AB - A previous study has shown that microRNA-708 (miR-708) functions as a metastasis
suppressor in ovarian cancer. In this study, we aimed to explore its implication
in regulating cisplatin sensitivity in ovarian cancer cells. To this end, ovarian
cancer cells were transfected with miR-708-expressing plasmids or vector before
treatment with different concentrations of cisplatin for 48 h. The 50% inhibitory
concentration (IC50 ) value was calculated. Apoptosis was analyzed by measuring
caspase-3 activity. The target gene mediating the function of miR-708 was
identified. Ectopic expression of miR-708 sensitized SKOV3 and A2780 cells to
cisplatin, decreasing the IC50 value by two- to threefold. miR-708 overexpression
significantly augmented cisplatin-induced apoptosis in ovarian cancer cells,
which was coupled with increased caspase-3 activity by two- to fourfold.
Similarly, overexpression of miR-708 increased the sensitivity of cisplatin
resistant SKOV3/DDP and A2780/DDP cells to cisplatin-induced toxicity, reducing
the IC50 by three- and fivefold, respectively. Delivery of miR-708 enhanced
cisplatin-induced elevation in caspase-3 activity in both cisplatin-resistant and
parental ovarian cancer cells. Mechanistically, miR-708 downregulated the
expression of insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) and
suppressed Akt phosphorylation. Silencing of IGF2BP1 markedly blocked the
phosphorylation of Akt. Overexpression of IGF2BP1 restored cisplatin resistance
and Akt phosphorylation in miR-708-overexpressing ovarian cancer cells.
Collectively, miR-708 increases the susceptibility of ovarian cancer cells to
cisplatin by targeting IGF2BP1 and inhibiting Akt signaling. Delivery of miR-708
may represent a promising strategy for improving cisplatin chemotherapy.
PMID- 28685896
TI - Comorbidity-dependent adherence to guidelines and survival in breast cancer-Is
there a role for guideline adherence in comorbid breast cancer patients? A
retrospective cohort study with 2137 patients.
AB - In the treatment of breast cancer, decisions on adjuvant treatment reflect
individual patient characteristics like age and comorbidity. This study assessed
the association between adherence to guidelines for adjuvant treatment and
survival while taking into account age at diagnosis and comorbidities. We
collected the Charlson comorbidity index at baseline for 2179 women treated for
primary breast cancer from 1992 to 2008 who participated in a German
retrospective multicenter cohort study. We assessed subsequent adjuvant therapy
guideline adherence and survival in relation to baseline comorbidities.
Guidelines for adjuvant chemotherapy and radiotherapy were more often violated in
patients with higher Charlson score. Patients with higher Charlson scores
received chemotherapy and radiotherapy less often and had higher rates of
mastectomy. Irrespective of comorbidity (Charlson score 0, 1-2, >=3), patients
with 100% guideline-adherent adjuvant treatment showed better overall and disease
free survival (DFS) compared to patients with guideline violations (GVs).
Controlling for age, comorbidity and tumor characteristics, the hazard ratio for
at least one GV was 1.65 (95% confidence interval [CI]: 1.33-2.07) for overall
survival and 1.84 (95% CI: 1.53-2.22) for DFS. Guideline-adherent treatment was
significantly less frequent in comorbid patients, although guideline adherence
was strongly associated with improved survival, irrespective of severity, and
number of comorbid diseases.
PMID- 28685897
TI - Complex sclerosing lesions and radial sclerosing lesions on core needle biopsy:
Low risk of carcinoma on excision in cases with clinical and imaging concordance.
AB - Complex or radial sclerosing lesions (CSL/RSL) are uncommon diagnoses on core
needle biopsy with a reported upgrade rate ranging between 0% and 23%. As a
result, their management remains controversial. In this study, we sought to
determine the rate of malignancy on excision for patients with pure CSL/RSL on
core biopsy, and to evaluate future breast cancer risk when CSL/RSL is managed
without excision. We retrospectively reviewed 118 cases of CSL/RSL diagnosed on
image-guided breast biopsies between 2005 and 2014 at our institution. Of 98
analyzed patients, 34 (35%) underwent excision and 64 (65%) were observed.
Demographic and clinical variables between excision and observation groups were
compared. In excised specimens, factors associated with upgrade to malignancy
were evaluated. The median age at diagnosis was 49 years (range, 27-88 years). In
the excision group, 3/34 cases were associated with malignancy, an overall
upgrade rate of 9%. All malignant cases had core needle biopsies interpreted as
discordant and were BIRADS 4B or more on imaging. In the observation group, at a
median follow-up of 2.2 years, 3/64 (5%) patients developed ipsilateral cancers,
all of which were distant from the index CSL/RSL. In our series, we report a 9%
malignancy rate on excision of BIRADS >4C lesions characterized as CSL/RSL on
core biopsy. In patients with concordant biopsies and BIRADS 4A or lower lesions
who underwent observation, we found a low rate of subsequent ipsilateral cancers.
Further studies are needed to confirm that for CSL/RSL in concordant core
biopsies and BIRADS 4A or lower, nonpalpable lesions, observation may be a
reasonable alternative to excision.
PMID- 28685898
TI - The Hsp40 J-domain modulates Hsp70 conformation and ATPase activity with a semi
elliptical spring.
AB - Regulatory protein interactions are commonly attributed to lock-and-key
associations that bring interacting domains together. However, studies in some
systems suggest that regulation is not achieved by binding interactions alone. We
report our investigations on specific physical characteristics required of the
Hsp40 J-domain to stimulate ATP hydrolysis in the Hsp40-Hsp70 molecular chaperone
machine. Biophysical analysis using isothermal titration calorimetry, and nuclear
magnetic resonance spectroscopy reveals the importance of helix rigidity for the
maintenance of Hsp40 function. Our results suggest that the functional J-domain
acts like a semi-elliptical spring, wherein the resistance to bending upon
binding to the Hsp70 ATPase modulates the ATPase domain conformational change and
promotes ATP hydrolysis.
PMID- 28685899
TI - Prevention and recognition of abusive head trauma: training for healthcare
professionals in Vietnam.
AB - AIM: This study presents results from an intervention designed to improve
identification and response to abusive head trauma in a tertiary paediatric
hospital in Vietnam. METHODS: One hundred and sixteen healthcare professionals
(paediatric medical and nursing staff) completed a clinical training programme
and participated in its evaluation. A pre-post-test and follow-up design was used
to evaluate the outcomes. Questionnaires were used to collect data prior to
training, at six weeks and at six months. Generalised linear modelling was used
to examine changes in diagnostic skills and knowledge of the consequences of
shaken baby syndrome (SBS) (a form of abusive head trauma), its prevention and
treatment. RESULTS: At baseline, awareness and knowledge reflected no former
abusive head trauma training. Following the intervention, participants had an
increased awareness of shaken baby syndrome and the potential consequences of
shaking infants and had acquired techniques to inform parents how to manage the
crying infant. CONCLUSION: The intervention was effective in raising awareness of
shaken baby syndrome and its consequences amongst the participating healthcare
professionals in Vietnam. Training can improve detection and prevention of
abusive head trauma, and the intervention has the potential to be adapted for
similar settings internationally.
PMID- 28685900
TI - Challenges the addiction field must overcome to avert being the Cinderella of
medicine.
PMID- 28685901
TI - Erosive pustular dermatosis of the scalp following topical ingenol mebutate for
actinic keratoses.
PMID- 28685902
TI - Can pay-for-performance to primary care providers stimulate appropriate use of
antibiotics?
AB - Antibiotic resistance is a major threat to public health worldwide. As the
healthcare sector's use of antibiotics is an important contributor to the
development of resistance, it is crucial that physicians only prescribe
antibiotics when needed and that they choose narrow-spectrum antibiotics, which
act on fewer bacteria types, when possible. Inappropriate use of antibiotics is
nonetheless widespread, not least for respiratory tract infections (RTI), a
common reason for antibiotics prescriptions. We examine if pay-for-performance
(P4P) presents a way to influence primary care physicians' choice of antibiotics.
During 2006-2013, 8 Swedish healthcare authorities adopted P4P to make physicians
select narrow-spectrum antibiotics more often in the treatment of children with
RTI. Exploiting register data on all purchases of RTI antibiotics in a difference
in-differences analysis, we find that P4P significantly increased the share of
narrow-spectrum antibiotics. There are no signs that physicians gamed the system
by issuing more prescriptions overall.
PMID- 28685904
TI - Second hydrogen atom abstraction by molecular ions.
AB - We report the observation of a new physical phenomenon of the addition of 2
hydrogen atoms to molecular ions thus forming [M + 2H]+ ions. We demonstrate such
second hydrogen atom abstraction onto the molecular ions of pentaerythritol and
trinitrotoluene (TNT). We used both gas chromatography mass spectrometry (GC-MS)
with supersonic molecular beam (SMB) with methanol added into its make-up gas and
electron ionization (EI) liquid chromatography mass spectrometry (LC-MS) with SMB
with methanol as the LC solvent. We found that the formation of methanol clusters
resulted upon EI in the formation of dominant protonated pentaerythritol ion at
m/z = 137 plus about 70% relative abundance of pentaerythritol molecular ion with
2 additional hydrogen atoms at m/z = 138 which is well above the 5.7% natural C13
isotope abundance of protonated pentaerythritol. Similarly, we found an abundant
protonated TNT ion at m/z = 228 and a similar abundance of TNT molecular ion with
2 additional hydrogen atoms at m/z = 229. Upon the use of deuterated methanol
(CD3 OD) as the solvent, we observed an abundant m/z = 231 (M + 2D)+ of TNT with
2 deuterium atoms. We found such abundant second hydrogen atom abstraction with
butylglycolate and at low abundances in dioctylphthalate, Vitamin K3, phenazine,
and RDX. At this time, we are unable to report the magnitude and frequency of
occurrence of this phenomenon in standard electrospray LC-MS. This observation
could have important implications on the provision of elemental formula from mass
spectra that are involved with protonated molecules. Accordingly, while accurate
mass measurements can serve for the generation of elemental formula, their
further support and improvement via isotope abundance analysis are questionable.
Consequently, if a given compound can be analyzed by both GC-MS and LC-MS, its GC
MS analysis can be superior for the provision of accurate elemental formulae if
its EI mass spectrum exhibits abundant molecular ions such as with GC-MS with SMB
(also known as cold EI).
PMID- 28685903
TI - The structure of RbmB from Streptomyces ribosidificus, an aminotransferase
involved in the biosynthesis of ribostamycin.
AB - Aminoglycoside antibiotics represent a classical group of antimicrobials first
discovered in the 1940s. Due to their ototoxic and nephrotoxic side effects, they
are typically only used against Gram negative bacteria which have become
resistant to other therapeutics. One family of aminoglycosides includes such
compounds as butirosin, ribostamycin, neomycin, and kanamycin, amongst others.
The common theme in these antibiotics is that they are constructed around a
chemically stable aminocyclitol unit referred to as 2-deoxystreptamine (2-DOS).
Four enzymes are required for the in vivo production of 2-DOS. Here, we report
the structure of RbmB from Streptomyces ribosidificus, which is a pyridoxal 5'
phosphate dependent enzyme that catalyzes two of the required steps in 2-DOS
formation by functioning on distinct substrates. For this analysis, the structure
of the external aldimine form of RbmB with 2-DOS was determined to 2.1 A
resolution. In addition, the structure of a similar enzyme, BtrR from Bacillus
circulans, was also determined to 2.1 A resolution in the same external aldimine
form. These two structures represent the first detailed molecular descriptions of
the active sites for those aminotransferases involved in 2-DOS production. Given
the fact that the 2-DOS unit is widespread amongst aminoglycoside antibiotics,
the data presented herein provide new molecular insight into the biosynthesis of
these sugar-based drugs.
PMID- 28685905
TI - 3D-modeling of carboxyl-terminal phosphorylation of plant alphabeta-tubulin and
its role in kinesin-8/microtubule interaction.
AB - The results of computer modeling of plant kinesin-8/alphabeta-tubulin complexes
with such alphabeta-tubulins' modified amino acid residues as phosphorylated
Tyr262 and Tyr107 are reported in this paper. The molecular dynamics of these
modified complexes in comparison with the dynamics of non-modified ones suggests
that the phosphorylation of both alpha- and beta-tubulins reveals stabilizing
effect on the protein structure around the modified residue. It was found also
that the phosphorylation of Tyr107 in beta-tubulin molecule favors to more
advantageous kinesin-8 binding with the phosphorylated microtubule surface in
terms of energy.
PMID- 28685906
TI - A morphology independent approach for identifying dividing adult neural stem
cells in the mouse hippocampus.
AB - BACKGROUND: Type 1 adult hippocampal neural stem cells (AH-NSCs) continue to
generate neurons throughout life, albeit at a very low rate. The relative
quiescence of this population of cells has led to many studies investigating
factors that may increase their division. Current methods of identifying dividing
AH-NSCs in vivo require the identification and tracing of radial processes back
to nuclei within the subgranular zone. However, caveats to this approach include
the time-intensive nature of identifying AH-NSCs with such a process, as well as
the fact that this approach ignores the relatively more active population of
horizontally oriented AH-NSCs that also reside in the subgranular zone. RESULTS:
Here we describe, and then verify using Hes5::GFP mice, that labeling for the
cell cycle marker Ki67 and selection against the intermediate progenitor cell
marker TBR2 (Ki67+ve ; TBR2-ve nuclei) is sufficient to identify dividing
horizontally and radially oriented AH-NSCs in the adult mouse hippocampus.
CONCLUSIONS: These findings provide a simple and accurate way to quantify
dividing AH-NSCs in vivo using a morphology-independent approach that will
facilitate studies into neurogenesis within the hippocampal stem cell niche of
the adult brain. Developmental Dynamics 247:194-200, 2018. (c) 2017 Wiley
Periodicals, Inc.
PMID- 28685907
TI - The gamma-glutamyl transpeptidase-to-albumin ratio predicts significant fibrosis
and cirrhosis in chronic hepatitis B patients.
AB - Background/Aim Simple, inexpensive and clinically available noninvasive liver
fibrosis tests are highly needed. We aimed to develop a novel noninvasive index
for predicting significant fibrosis and cirrhosis in chronic hepatitis B (CHB)
patients. Methods Using liver histology as gold standard, we developed a novel
index to predict significant fibrosis and cirrhosis in CHB patients and then
compared the diagnostic accuracy of the novel index, aspartate transaminase-to
platelet ratio index (APRI), and fibrosis index based on four factors (FIB-4) in
a training set (606 patients) and a validation set (216 patients) from the same
patient catchment area. Results Of 606 CHB patients in the training set, 33.2%
had significant fibrosis and 11.4% had cirrhosis. In multivariable analysis,
gamma-glutamyl transpeptidase (GGT) (OR=1.032, p<0.001) and albumin (OR=0.953,
p=0.048) were independent predictors of significant fibrosis. Consequently, a GGT
to-albumin ratio (GAR) was developed. In the training set, the area under the
receiver operating characteristic curve (AUROC) of GAR was significantly higher
than that of APRI and FIB-4 to predict >=F2 (0.82, 0.70, and 0.68, respectively),
>=F3 (0.86, 0.76, and 0.75, respectively), and F4 (0.88, 0.75, and 0.73,
respectively), respectively. In the validation set, the AUROC of GAR was also
better than APRI and FIB-4 for predicting >=F2 (0.81, 0.63 and 0.61,
respectively), >=F3 (0.88, 0.78, and 0.76, respectively) and F4 (0.92, 0.85, and
0.78, respectively), respectively. Conclusions GAR is a more accurate noninvasive
index than APRI and FIB-4 to stage significant fibrosis and cirrhosis in CHB
patients and represents a novel noninvasive alternative to liver biopsy.
PMID- 28685908
TI - Trifluoromethylation of a Well-Defined Square-Planar Aryl-NiII Complex involving
NiIII /CF3. and NiIV -CF3 Intermediate Species.
AB - Ni-mediated trifluoromethylation of an aryl-Br bond in model macrocyclic ligands
(Ln -Br) has been thoroughly studied, starting with an oxidative addition at Ni0
to obtain well-defined aryl-NiII -Br complexes ([Ln -NiII ]Br). Abstraction of
the halide with AgX (X=OTf- or ClO4- ) thereafter provides [Ln -NiII ](OTf). The
nitrate analogue has been obtained through a direct C-H activation of an aryl-H
bond using NiII salts, and this route has been studied by X-ray absorption
spectroscopy (XAS). Crystallographic XRD and XAS characterization has shown a
tight macrocyclic coordination in the aryl-NiII complex, which may hamper direct
reaction with nucleophiles. On the contrary, enhanced reactivity is observed with
oxidants, and the reaction of [Ln -NiII ](OTf) with CF3+ sources afforded Ln -CF3
products in quantitative yield. A combined experimental and theoretical
mechanistic study provides new insights into the operative mechanism for this
transformation. Computational analysis indicates the occurrence of an initial
single electron transfer (SET) to 5-(trifluoromethyl)dibenzothiophenium triflate
(TDTT), producing a transient L1 -NiIII /CF3. adduct, which rapidly recombines to
form a [L1 -NiIV -CF3 ](X)2 intermediate species. A final facile reductive
elimination affords L1 -CF3 . The well-defined square-planar model system studied
here permits to gain fundamental knowledge on the rich redox chemistry of nickel,
which is sought to facilitate the development of new Ni-based
trifluoromethylation methodologies.
PMID- 28685909
TI - Multisite musculoskeletal pain in adolescence as a predictor of medical and
social welfare benefits in young adulthood: The Norwegian Arctic Adolescent
Health Cohort Study.
AB - BACKGROUND: Pain in adolescence is associated with mental health problems, the
main reason for work disability in young adults. This study explores the
relationship between multisite musculoskeletal pain in adolescence and later
medical (sickness and medical rehabilitation benefits) and social welfare
benefits, adjusted for sociodemographic, adolescent psychosocial and mental
health problems. METHODS: Data were obtained by linkage between the National
Insurance Registry (2003-11) and the Norwegian Arctic Adolescent Health Study, a
school-based survey in North Norway (2003-05), accepted by 3987 fifteen- to
sixteen-year-olds (68% of the total population). The start of the follow-up time
was July 1st of the corresponding year the participants responded to the health
study. Musculoskeletal pain was measured by the number of musculoskeletal pain
sites. RESULTS: We found a positive linear relationship between adolescent
musculoskeletal pain sites and the occurrence of medical and social welfare
benefits in young adulthood (p <= 0.001). Adolescent musculoskeletal pain was a
significant predictor of sickness (p < 0.001) and social welfare benefits in
females (p = 0.036), when adjusted for adolescent psychosocial and mental health
problems. The most important adolescent psychosocial predictors were
externalizing problems, less parental involvement and adverse life events.
CONCLUSION: Adolescent multisite musculoskeletal pain was found to be an
important predictor of later sickness and social welfare benefit receipt from
adolescence to young adulthood. SIGNIFICANCE: Adolescents with multisite
musculoskeletal pain are at substantially increased risk of health and social
difficulties into young adulthood. Identification and interventions for these
adolescent problems could alleviate this risk and be a sound socioeconomic
investment.
PMID- 28685910
TI - The independent influences of age and education on functional brain networks and
cognition in healthy older adults.
AB - Healthy aging is accompanied by a constellation of changes in cognitive processes
and alterations in functional brain networks. The relationships between brain
networks and cognition during aging in later life are moderated by demographic
and environmental factors, such as prior education, in a poorly understood
manner. Using multivariate analyses, we identified three latent patterns (or
modes) linking resting-state functional connectivity to demographic and cognitive
measures in 101 cognitively normal elders. The first mode (P = 0.00043) captures
an opposing association between age and core cognitive processes such as
attention and processing speed on functional connectivity patterns. The
functional subnetwork expressed by this mode links bilateral sensorimotor and
visual regions through key areas such as the parietal operculum. A strong,
independent association between years of education and functional connectivity
loads onto a second mode (P = 0.012), characterized by the involvement of key hub
regions. A third mode (P = 0.041) captures weak, residual brain-behavior
relations. Our findings suggest that circuits supporting lower level cognitive
processes are most sensitive to the influence of age in healthy older adults.
Education, and to a lesser extent, executive functions, load independently onto
functional networks-suggesting that the moderating effect of education acts upon
networks distinct from those vulnerable with aging. This has important
implications in understanding the contribution of education to cognitive reserve
during healthy aging. Hum Brain Mapp 38:5094-5114, 2017. (c) 2017 Wiley
Periodicals, Inc.
PMID- 28685912
TI - Understanding Noncovalent Interactions of Small Molecules with Carbon Nanotubes.
AB - We combine experimental methods, density functional theory (DFT) calculations,
and molecular dynamics (MD) simulations in the quantitative analysis of
noncovalent interactions between (6,5)-enriched single-walled carbon nanotubes
(SWNTs), as hosts, and a set of pyrene derivatives with different electronic
properties and surface areas, as guests. The experiments and calculations were
carried out in two solvents with markedly different polarities, namely 1,1',2,2'
tetrachloroethane (TCE) and N,N-dimethylformamide (DMF). Our results show that
dispersion forces govern the supramolecular association of small molecules with
(6,5)-SWNTs, with negligible contributions from ground-state charge-transfer
effects. In the nonpolar solvent (TCE), the binding constants are highly
correlated with the contact area between the SWNT and the guests. In the polar
solvent (DMF), the binding constants show a complex dependence on the chemical
nature of the pyrene substituents, as demonstrated by MD simulations with the
explicit inclusion of solvent molecules. The solvation of the small molecules is
shown to play a leading role in the binding process. Remarkably, the binding
constants obtained from the MD simulations for the five guest molecules correlate
with those derived from experiment. Furthermore, the MD simulations also reveal
the structure of the adsorbed guest from low to high SWNT surface coverage.
PMID- 28685911
TI - Combined Lifestyle and Herbal Medicine in Overweight Women with Polycystic Ovary
Syndrome (PCOS): A Randomized Controlled Trial.
AB - Polycystic ovary syndrome (PCOS) is a common, complex reproductive endocrinopathy
characterized by menstrual irregularities, hyperandrogenism and polycystic
ovaries. Lifestyle modification is a first-line intervention; however, there are
barriers to success for this form of self-care, and women often seek adjunct
therapies including herbal medicines. This pragmatic, randomized controlled
trial, delivered in communities of Australia in overweight women with PCOS,
compared the effectiveness and safety of a lifestyle intervention plus herbal
medicine against lifestyle alone. All participants were helped to construct a
personalized lifestyle plan. The herbal intervention consisted of two tablets.
Tablet 1 contained Cinnamomum verum, Glycyrrhiza glabra, Hypericum perforatum and
Paeonia lactiflora. Tablet 2 contained Tribulus terrestris. The primary outcome
was oligomenorrhoea/amenorrhoea. Secondary outcomes were hormones; anthropometry;
quality of life; depression, anxiety and stress; pregnancy; birth outcomes; and
safety. One hundred and twenty-two women gave their consent. At 3 months, women
in the combination group recorded a reduction in oligomenorrhoea of 32.9% (95%
confidence interval 23.3-42.6, p < 0.01) compared with controls, estimated as a
large effect (etap2 = 0.11). Other significant improvements were found for body
mass index (p < 0.01); insulin (p = 0.02) and luteinizing hormone (p = 0.04);
blood pressure (p = 0.01); quality of life (p < 0.01); depression, anxiety and
stress (p < 0.01); and pregnancy rates (p = 0.01). This trial provides evidence
of improved effectiveness and safety for lifestyle intervention when combined
with herbal medicines in women with PCOS. (c) 2017 The Authors. Phytotherapy
Research published by John Wiley & Sons Ltd.
PMID- 28685913
TI - Could phase 3 medicine trials be tagged as pragmatic? A case study: The Salford
COPD trial.
AB - Randomized clinical trials (RCTs) can be classified as explanatory or pragmatic.
Currently, explanatory and pragmatic are considered to be the extremes of a
continuum: Many trials have some features of both explanatory and pragmatic RCTs.
The Salford Chronic Obstructive Respiratory Disease (COPD) trial was an open
label phase 3 RCT assessing an experimental product (fluticasone furoate
vilanterol) vs usual care. The Salford investigators labelled it as "the world's
first phase 3 pragmatic RCT" in COPD patients. The evaluation of the Salford
trial by means of the PRECIS-2 tool, yielded a mix of both extremes (explanatory
and pragmatic) with several of the 9 domains close to the explanatory extreme and
few to the pragmatic one. A number of the features could not be considered as
being minimal changes over usual clinical practice. Hence, it would be difficult
to accept that the Salford COPD trial was a pragmatic RCT. In addition, all trial
participants could have been subject to the Hawthorne effect. The scientific
community needs to be rigorous enough when using certain terms related to RCT. It
is clear that the Salford COPD trial had particular features-sharing some of
explanatory phase 3 RCTs and some of pragmatic RCTs. This, however, is not enough
to tag it as a "pragmatic" RCT providing "real-world" data. These words should
not be used when referring to prelicensed RCT, unless they really describe how
was the trial conducted and the type of data gathered-something that with the
current clinical trial regulations will only occur in very rare circumstances.
PMID- 28685914
TI - Rates of liver retransplantation in the United States are declining in the era of
direct-acting antiviral agents.
PMID- 28685916
TI - Human genetic factors in tuberculosis: an update.
AB - Tuberculosis (TB) is a major threat to human health, especially in many
developing countries. Human genetic variability has been recognised to be of
great relevance in host responses to Mycobacterium tuberculosis infection and in
regulating both the establishment and the progression of the disease. An
increasing number of candidate gene and genome-wide association studies (GWAS)
have focused on human genetic factors contributing to susceptibility or
resistance to TB. To update previous reviews on human genetic factors in TB we
searched the MEDLINE database and PubMed for articles from 1 January 2014 through
31 March 2017 and reviewed the role of human genetic variability in TB. Search
terms applied in various combinations were 'tuberculosis', 'human genetics',
'candidate gene studies', 'genome-wide association studies' and 'Mycobacterium
tuberculosis'. Articles in English retrieved and relevant references cited in
these articles were reviewed. Abstracts and reports from meetings were also
included. This review provides a recent summary of associations of polymorphisms
of human genes with susceptibility/resistance to TB.
PMID- 28685917
TI - On the potential of a short-term intensive intervention to interrupt HCV
transmission in HIV-positive men who have sex with men: A mathematical modelling
study.
AB - Increasing access to direct-acting antiviral (DAA) treatment for hepatitis C
virus (HCV) infection and decelerating the rise in high-risk behaviour over the
next decade could curb the HCV epidemic among HIV-positive men who have sex with
men (MSM). We investigated if similar outcomes would be achieved by short-term
intensive interventions like the Swiss-HCVree-trial. We used a HCV transmission
model emulating two 12-months intensive interventions combining risk counselling
with (i) universal DAA treatment (pangenotypic intervention) and (ii) DAA
treatment for HCV genotypes 1 and 4 (replicating the Swiss-HCVree-trial). To
capture potential changes outside intensive interventions, we varied time from
HCV infection to treatment in clinical routine and overall high-risk behaviour
among HIV-positive MSM. Simulated prevalence dropped from 5.5% in 2016 to <=2.0%
over the intervention period (June/2016-May/2017) with the pangenotypic
intervention, and to <=3.6% with the Swiss-HCVree-trial. Assuming time to
treatment in clinical routine reflected reimbursement restrictions (METAVIR >=F2,
16.9 years) and stable high-risk behaviour in the overall MSM population,
prevalence in 2025 reached 13.1% without intensive intervention, 11.1% with the
pangenotypic intervention and 11.8% with the Swiss-HCVree-trial. If time to
treatment in clinical routine was 2 years, prevalence in 2025 declined to 4.8%
without intensive intervention, to 2.8% with the pangenotypic intervention, and
to 3.5% with the Swiss-HCVree-trial. In this scenario, the pangenotypic
intervention and the Swiss-HCVree-trial reduced cumulative (2016-2025) treatment
episodes by 36% and 24%, respectively. Therefore, intensive interventions could
reduce future HCV treatment costs and boost the benefits of long-term efforts to
prevent high-risk behaviour and to reduce treatment delay. But if after intensive
interventions treatment is deferred until F2, short-term benefits of intensive
interventions would dissipate in the long term.
PMID- 28685919
TI - Sleep in neurological disorders, sleep apnea, sleep duration and body weight.
PMID- 28685918
TI - A Long-Term BCI Study With ECoG Recordings in Freely Moving Rats.
AB - BACKGROUND: Brain Computer Interface (BCI) studies are performed in an increasing
number of applications. Questions are raised about electrodes, data processing
and effectors. Experiments are needed to solve these issues. OBJECTIVE: To
develop a simple BCI set-up to easier studies for improving the mathematical
tools to process the ECoG to control an effector. METHOD: We designed a simple
BCI using transcranial electrodes (17 screws, three mechanically linked to create
a common reference, 14 used as recording electrodes) to record Electro-Cortico
Graphic (ECoG) neuronal activities in rodents. The data processing is based on an
online self-paced non-supervised (asynchronous) BCI paradigm. N-way partial least
squares algorithm together with Continuous Wavelet Transformation of ECoG
recordings detect signatures related to motor activities. Signature detection in
freely moving rats may activate external effectors during a behavioral task,
which involved pushing a lever to obtain a reward. RESULTS: After routine
training, we showed that peak brain activity preceding a lever push (LP) to
obtain food reward was located mostly in the cerebellar cortex with a higher
correlation coefficient, suggesting a strong postural component and also in the
occipital cerebral cortex. Analysis of brain activities provided a stable
signature in the high gamma band (~180Hz) occurring within 1500 msec before the
lever push approximately around -400 msec to -500 msec. Detection of the
signature from a single cerebellar cortical electrode triggers the effector with
high efficiency (68% Offline and 30% Online) and rare false positives per minute
in sessions about 30 minutes and up to one hour (~2 online and offline).
CONCLUSIONS: In summary, our results are original as compared to the rest of the
literature, which involves rarely rodents, a simple BCI set-up has been developed
in rats, the data show for the first time long-term, up to one year, unsupervised
online control of an effector.
PMID- 28685921
TI - Prediction of outcome after curative surgery for colorectal cancer: preoperative
haemoglobin, C-reactive protein and albumin.
AB - AIM: The aim was to evaluate a scoring system using the values of preoperative
haemoglobin, C-reactive protein (CRP) and albumin to predict colorectal cancer
recurrence and survival. METHOD: Data on all curative resections for Stages I-III
colorectal cancer performed at a tertiary referral hospital in 2007-2010 were
recorded in the Swedish Colorectal Cancer Registry and were matched to local
databases for laboratory results and blood transfusion. Patients who died within
30 days or during primary hospital admission were excluded. Preoperative
haemoglobin, CRP and albumin levels were recorded for 417 patients. A score (0-3)
was derived on the presence of anaemia (Hb < 120 g/l for women and < 130 g/l for
men), raised CRP (> 10 mg/ml) and low albumin (< 35 g/dl). The risks for
recurrence and impaired overall survival were assessed using Cox regression
analyses. RESULTS: Impaired overall survival was found when one, two or three of
the criteria anaemia, elevated CRP and low albumin were present prior to surgery
[hazard ratio (HR) 3.61, 95% CI 1.66-7.85; HR 3.91, 95% CI 1.75-8.74; HR 4.85,
95% CI 2.15-10.93, respectively]. The risk for recurrence, however, was not
related to the presence of these criteria. CONCLUSION: Overall survival after
curative surgery for Stages I-III colorectal cancer is impaired when anaemia,
elevated CRP or low albumin exist prior to surgery.
PMID- 28685920
TI - Bridging the Gap between Industrial and Well-Defined Supported Catalysts.
AB - Many industrial catalysts contain isolated metal sites on the surface of oxide
supports. Although such catalysts have been used in a broad range of processes
for more than 40 years, there is often a very limited understanding about the
structure of the catalytically active sites. This Review discusses how surface
organometallic chemistry (SOMC) engineers surface sites with well-defined
structures and provides insight into the nature of the active sites of industrial
catalysts; the Review focuses in particular on olefin production and conversion
processes.
PMID- 28685922
TI - Models, action and progress in psychology and chronic pain.
PMID- 28685923
TI - Interactions and effects of metal oxide nanoparticles on microorganisms involved
in biological wastewater treatment.
AB - To clarify the toxicological effects of metal oxide nanoparticles (NPs) on
microorganisms with environmental relevance, it is necessary to understand their
interactions. In this work, they were studied the effects and the morphological
interactions of two metal oxide NPs (ZnO and TiO2 ) with microorganisms, during
aerobic treatment of wastewater. The effects were evaluated according to nutrient
removal from wastewater, while morphological interactions were determined by
three different techniques such as TEM, HAADF-STEM, as well as an elemental
mapping. According to results about effects of both NPs, they inhibited the
removal of organic matter and ammonia nitrogen, and enhanced the orthophosphate
removal. Related to morphological interactions, the electron-dense material of
both NPs was mainly observed bounded to cell membrane. In tests with ZnO NPs, it
was also observed electron-dense material internalized in microorganisms without
physical damage in cell membrane. The elemental mapping was useful to determine
that the electron-dense material corresponded to Zn and Ti. Both interactions,
internalization and attachment of NPs on cell membrane of microorganisms may
trigger the negative effect in the removal of organic matter and nitrogen.
PMID- 28685924
TI - Combining albumin-bilirubin score with future liver remnant predicts post
hepatectomy liver failure in HBV-associated HCC patients.
AB - BACKGROUND AND AIMS: Accurate assessment of liver functional reserve pre
operatively is vital for safe hepatic resection. The ALBI score is a new model
for assessing liver function. This study aimed to evaluate the value of combining
ALBI score with sFLR in predicting post-operative morbidity and PHLF in HCC
patients who underwent hepatectomy. METHODS: Patients undergoing three
dimensional CT reconstruction prior to hepatectomy for HCC between January 2015
and January 2017 were enrolled. The values of the CP score, ALBI score and sFLR
in predicting post-operative outcomes were evaluated. RESULTS: A total of 229 HCC
patients were enrolled; 24 (10.5%) experienced major complications and 21 (9.2%)
developed PHLF. The incidence of major complications and PHLF increased with
increasing ALBI grade. The ALBI grade classified patients with CP grade A into
two subgroups with different incidences of PHLF (P=.029). sFLR and ALBI scores
were identified as independent predictors of PHLF. The AUC values for the CP
score, ALBI score, sFLR and sFLR*ALBI for predicting major complications were
0.600, 0.756, 0.660 and 0.790 respectively. The AUC values of the CP score, ALBI
score, sFLR and sFLR*ALBI for predicting PHLF were 0.646, 0.738, 0.758 and 0.884
respectively. CONCLUSIONS: The ALBI score showed superior predictive value of
post-operative outcomes over CP score, and the combination of sFLR and ALBI score
was identified as a stronger predictor of post-operative outcomes than the sFLR
or ALBI score alone.
PMID- 28685925
TI - What goes wrong with the allocation of domestic and international resources for
HIV?
AB - This paper examines how domestic and international financing for HIV is, and
ought to be, distributed. We build a theoretical framework that decomposes
domestic and international financing for HIV into nonlinear functions of national
income, HIV prevalence, and government effectiveness. We test this model, paying
particular attention to nonlinearities and to problems of bad controls,
multicollinearity, and reverse causality. Finally, we use the fitted values of
quartile regressions to study how much countries could reasonably pay
domestically and how much they should receive from donors. Worryingly, countries
with higher financial means receive on average more aid per PLHIV than very poor
ones, and countries with higher HIV prevalence receive on average less aid per
people living with HIV. The normative analysis concludes that US$3.08 billion of
fiscal space could be created in LIC and MIC. We identify the countries that
could be allocated more aid.
PMID- 28685926
TI - Living with systemic lupus erythematosus: A patient engagement perspective.
AB - Patient engagement is recognized as a crucial component of high-quality
healthcare services. Among rheumatic diseases, systemic lupus erythematosus (SLE)
appears particularly challenging for the engagement of patients in their own
care. According to the patient health engagement (PHE) model, patient engagement
is a dynamic phenomenon that proceeds through four experiential positions
(blackout, arousal, adhesion and eudaimonic project). The aim of the present
study was to describe the engagement process from the point of view and the
experiences of SLE patients. Ten in-depth interviews and four focus groups were
conducted with an international sample of SLE patients from different European
countries. Transcripts were analysed through thematic content analysis. Findings
showed that a fully engaged patient results from reframing emotional, cognitive
and behavioural dimensions. The advances along the process depends on how the
patient succeeds in each position. In conclusion, PHE represents an appropriate
model by which to understand the engagement process of SLE patients. In order to
meet patients' needs, healthcare providers and patient support groups should
consider the specific position of SLE patients, providing adequate and tailored
support.
PMID- 28685928
TI - Management of patients with previously untreated chronic lymphocytic leukaemia
with obinutuzumab and chlorambucil.
AB - Patients with chronic lymphocytic leukaemia (CLL) are generally older, with many
considered 'unfit' for fludarabine-cyclophosphamide-rituximab therapy. In these
patients, the combination of obinutuzumab-chlorambucil may be an appropriate
therapeutic choice. Obinutuzumab-chlorambucil has been demonstrated to improve
overall survival rates compared to chlorambucil alone and to improve progression
free survival and overall response rates compared to rituximab-chlorambucil. This
combination can lead to certain toxicities that need to be addressed through
appropriate patient selection, pre-medication and management. In this paper, we
discuss evidence-based and author-recommended practical management of first-line
CLL patients receiving obinutuzumab-chlorambucil.
PMID- 28685927
TI - Altering equine corneal fibroblast differentiation through Smad gene transfer.
AB - OBJECTIVE: To explore the impact of equine corneal fibroblast (ECF) to
myofibroblast (ECM) differentiation by altering the expression of the Smad genes
either individually or in combination. Specifically, we sought to examine the ECF
differentiation after (a) silencing of Smad2, 3, and 4 profibrotic genes
individually and (b) overexpression of antifibrotic Smad7 gene and in a
combination with pro- and antifibrotic Smad genes. METHODS: Equine corneal
fibroblast primary cultures were generated as previously described. ECFs were
transfected with individual plasmids which silenced gene expression of either
Smad2, 3, or 4 or in combination with a plasmid overexpressing Smad7 using
Lipofectamine 2000TM or Lipofectamine BLOCK-iTTM. Smad-transfected clones were
then exposed to TGF-beta1 to induce differentiation to myofibroblasts.
Immunofluorescence and qRT-PCR techniques quantified levels of ECF
differentiation to ECM by measuring alpha smooth muscle actin, a known marker of
ECM transdifferentiation. RESULTS: Silencing of individual Smad2, 3, or 4 genes
or overexpression of Smad7 showed significant inhibition of ECF
transdifferentiation (73-83% reduction). Silencing of Smad2 showed the greatest
inhibition of ECF transdifferentiation in (a) and was therefore utilized for the
combination gene transfer testing. The combination gene transfer consisting of
Smad7 overexpression and Smad2 silencing attenuated ECF differentiation
significantly; however, the level was not significant compared to the
overexpression of Smad7 individually. CONCLUSIONS: Using gene transfer technology
involving profibrotic Smad silencing, antifibrotic Smad overexpression or its
combination is a novel strategy to control TGF-beta1-mediated fibrosis in equine
fibroblasts. Combination gene therapy was not better than single gene therapy in
this study.
PMID- 28685929
TI - Erratum: "Estimating organ doses from tube current modulated CT examinations
using a generalized linear model" [Med. Phys. Vol 44 (4), 1500-1513 (2017)].
PMID- 28685930
TI - Paediatric obesity treatment had better outcomes when children were younger, well
motivated and did not have acanthosis nigricans.
AB - AIM: This study evaluated the efficacy of a paediatric obesity treatment
programme and explored the factors that contributed to the outcome. METHODS: We
recorded the body mass index standard deviation scores (BMI SDS) of 654 children
aged 2-18 years who were treated for obesity in 2005-2012 in three Finnish
hospitals, one year before treatment and up to three years after treatment. The
family-based multidisciplinary treatment included nutritional advice, exercise
and behavioural counselling. The BMI SDS changes, and their contributors, were
explored with mixed-model and logistic regression analyses. RESULTS: BMI SDS
increased before baseline and decreased at six, 12 and 24 months (all p < 0.001)
and 36 months (p = 0.005). Younger age (p < 0.001), higher BMI SDS at baseline (p
= 0.001), motivation (p = 0.013), adherence to the protocol (p = 0.033) and lack
of acanthosis nigricans (p < 0.001) improved the outcome. The BMI SDS of children
aged 2-6 decreased best from baseline to 12 (-0.35), 24 (-0.58) and 36 months (
0.64) (all p < 0.001). CONCLUSION: Paediatric obesity treatment was most
effective at a younger age. Good motivation and adherence contributed to
favourable outcomes, while acanthosis nigricans was associated with a poor
outcome.
PMID- 28685931
TI - Structure of the WD40-domain of human ATG16L1.
AB - Autophagy-related protein ATG16L1 is a component of the mammalian
ATG12~ATG5/ATG16L1 complex, which acts as E3-ligase to catalyze lipidation of LC3
during autophagosome biogenesis. The N-terminal part of ATG16L1 comprises the
ATG5-binding site and coiled-coil dimerization domain, both also present in yeast
ATG16 and essential for bulk and starvation induced autophagy. While absent in
yeast ATG16, mammalian ATG16L1 further contains a predicted C-terminal WD40
domain, which has been shown to be involved in mediating interaction with diverse
factors in the context of alternative functions of autophagy, such as
inflammatory control and xenophagy. In this work, we provide detailed information
on the domain boundaries of the WD40-domain of human ATG16L1 and present its
crystal structure at a resolution of 1.55 A.
PMID- 28685932
TI - Usage of a dataset of NMR resolved protein structures to test aggregation versus
solubility prediction algorithms.
AB - There has been an increased interest in computational methods for amyloid and
(or) aggregate prediction, due to the prevalence of these aggregates in numerous
diseases and their recently discovered functional importance. To evaluate these
methods, several datasets have been compiled. Typically, aggregation-prone
regions of proteins, which form aggregates or amyloids in vivo, are more than 15
residues long and intrinsically disordered. However, the number of such
experimentally established amyloid forming and non-forming sequences are limited,
not exceeding one hundred entries in existing databases. In this work, we parsed
all available NMR-resolved protein structures from the PDB and assembled a new,
sevenfold larger, dataset of unfolded sequences, soluble at high concentrations.
We proposed to use these sequences as a negative set for evaluating methods for
predicting aggregation in vivo. We also present the results of benchmarking
cutting edge tools for the prediction of aggregation versus solubility
propensity.
PMID- 28685933
TI - Comparative analysis of 15 chemical constituents in Scutellaria baicalensis stem
leaf from different regions in China by ultra-high performance liquid
chromatography with triple quadrupole tandem mass spectrometry.
AB - Scutellaria baicalensis is a traditional Chinese herbal medicine containing
multiple components, which has been extensively used in clinics to treat epidemic
febrile disease and hyperactivity cough. To get a deeper understanding about
Scutellaria baicalensis stem-leaf resources, we analyzed 15 chemical constituents
in 35 batches of Scutellaria baicalensis stem-leaf from eight regions in China. A
rapid, simple, and sensitive method using ultra-high performance liquid
chromatography coupled with triple quadrupole electrospray tandem mass
spectrometry has been developed for the first time to simultaneously determine 15
chemical constituents (including phenolic acids and flavonoids) in Scutellaria
baicalensis stem-leaf. Sufficient separation of 15 target constituents was
achieved on a Waters Acquity UPLC BEH C18 (2.1 mm * 100 mm, 1.7 MUm) column
within 14 min under the optimized chromatographic conditions. The established
method was validated and showed good linearity, precision, repeatability,
stability, and recovery and was successfully applied for the simultaneous
determination of the 15 chemical constituents in these samples. Hierarchical
clustering analysis and principal components analysis were performed to estimate
and classify these samples based on the contents of the 15 chemical constituents.
This study provided theoretical basis and scientific evidence for the development
and utilization of Scutellaria baicalensis stem-leaf resources.
PMID- 28685934
TI - Does SGLT2 inhibition with dapagliflozin overcome individual therapy resistance
to RAAS inhibition?
AB - Individual patients show a large variation in their response to renin-angiotensin
aldosteron system (RAAS) inhibition (RAASi), both in surrogates such as
albuminuria and in hard renal outcomes. Sodium-glucose co-transporter 2
inhibitors (SGLT2) have been shown to lower albuminuria and to confer
cardiovascular and, possibly, renal protection. To establish whether individual
therapy resistance to RAASi can be overcome by adding an SGLT2 inhibitor, we
assessed individual albuminuria responses in patients exposed to both RAASi and
the SGLT2 inhibitor dapagliflozin. We used data from a randomized controlled
cross-over trial designed to assess the albuminuria-lowering effect of 6-week
treatment with dapagliflozin 10 mg/d. We extracted from the electronic medical
records data on the albuminuria response upon initiation of RAASi before the
trial period, and analysed individual albuminuria responses to RAASi and to
dapagliflozin. We retrieved data on RAASi for 26 patients (age, 62 years [SD, 8];
female gender, 6 [23%]; 24-hour urinary albumin excretion, 521 [187-921] mg/24
h). The mean albuminuria-lowering response to RAASi was 26.5% (range, -76.1% to
135.1%). The addition of dapagliflozin res in a further reduction of 34.9%,
(range, -83.9 to 94.2). Interestingly, the albuminuria response to RAASi
significantly correlated with the response to dapagliflozin (Pearson correlation
coefficient, 0.635 [95% CI, 0.328-0.821]; P < .001), indicating that patients who
did not respond to RAASi also did not respond to dapagliflozin. We concluded that
individual therapy resistance to RAASi cannot be overcome with the addition of a
completely different class of drugs, SGLT2 inhibitors. These data suggest that
the individual drug response is an intrinsic individual characteristic, possibly
unrelated to the type of intervention, unless the mode of action of dapagliflozin
on albuminuria is through the RAAS.
PMID- 28685935
TI - Gastric gland mucin-specific O-glycan expression decreases with tumor progression
from precursor lesions to pancreatic cancer.
AB - Pancreatic cancer is lethal, as it is often detected late. Thus, novel biomarkers
of precursor lesions are needed to devise timely therapies. Pancreatic
intraepithelial neoplasia (PanIN) and intraductal papillary mucinous neoplasm
(IPMN) are major precursors of pancreatic cancer. In normal gastric mucosa,
gastric gland mucin-specific O-glycans are unique in having alpha1,4-linked N
acetylglucosamine (alphaGlcNAc) residues attached to MUC6. Recently we reported
that alphaGlcNAc functions as a tumor suppressor for differentiated-type gastric
adenocarcinoma (Karasawa et al., J Clin Invest 122, 923, 2012). MUC6 is also
expressed in pancreatic neoplasms, including PanIN and IPMN, but the role of
alphaGlcNAc expression in pancreatic neoplasms remains unknown. Here, we analyze
expression patterns of alphaGlcNAc, MUC6 and MUC5AC in pancreatic neoplasms and
compare them with progression from PanIN to invasive ductal adenocarcinoma (IDAC)
(the PanIN-IDAC sequence; 20 cases) and from IPMN to IPMN with associated
invasive carcinoma (IPMNAIC) (the IPMN-IPMNAIC sequence; 20 cases). At both
sequences, the frequency of MUC6-positive and alphaGlcNAc-positive lesions
decreased with tumor progression. We then compared expression levels of
alphaGlcNAc and MUC6 at each step of the progression. At the PanIN-IDAC sequence,
alphaGlcNAc expression significantly decreased relative to MUC6 in low-grade
PanIN (P = 0.021), high-grade PanIN/intraductal spread of IDAC (P = 0.031) and
IDAC (P = 0.013). At the IPMN-IPMNAIC sequence, decreased alphaGlcNAc expression
was also observed in low-grade IPMN exhibiting gastric-type morphology (P =
0.020). These results suggest that decreased expression of alphaGlcNAc relative
to MUC6 occurs early and marks the initiation of tumor progression to pancreatic
cancer.
PMID- 28685936
TI - Adapting the Glaser Reaction for Bioconjugation: Robust Access to Structurally
Simple, Rigid Linkers.
AB - Copper-mediated coupling between alkynes to generate a structurally rigid, linear
1,3-diyne linkage has been known for over a century. However, the mechanistic
requirement to simultaneously maintain CuI and an oxidant has limited its
practical utility, especially for complex functional molecules in aqueous
solution. We find that addition of a specific bpy-diol ligand protects
unprotected peptides from CuII -mediated oxidative damage through the formation
of an insoluble CuII gel which solves the critical challenge of applying Glaser
coupling to substrates that are degraded by CuII . The generality of this method
is illustrated through the conjugation of a series of polar and nonpolar labels
onto a fully unprotected GLP-1R agonist through a linear 7 A diynyl linker.
PMID- 28685937
TI - Neuroimmunomodulatory properties of DPSCs in an in vitro model of Parkinson's
disease.
AB - In neurodegenerative diseases, such as Alzheimer's and Parkinson's, microglial
cell activation is thought to contribute to their degeneration by producing
neurotoxic compounds. While dental pulp stem cells (DPSCs) have been regarded as
the next possible cell source for cell replacement therapy (CRT), their actual
role when exposed in such harsh environment remains elusive. In this study, the
immunomodulatory behavior of DPSCs from human subjects was investigated in a
coculture system consisting of neuron and microglia which were treated with 1
methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine, which mimics the inflammatory
conditions and contribute to degeneration of dopaminergic (DA-ergic) neurons.
Assessments were performed on their proliferation, extent of DNA damage,
productions of reactive oxygen species (ROS) and nitric oxide (NO), as well as
secretion of inflammatory mediators. Notably, DPSCs were shown to attenuate their
proliferation, production of ROS, and NO significantly (P < 0.05). Additionally,
their immunomodulatory properties were distinct although insignificant changes
were observed in DNA damage. Despite DPSCs were exposed to such harsh
environment, they were still able to express neuronal markers such as Nestin, Pax
6, and Nurr1, at least by twofold thereby indicating their applicability for CRT
especially in PD conditions. To conclude, DPSCs were shown to have
immunomodulatory capacities which could probably serve as secondary effects upon
transplantation in a CRT regime. (c) 2017 IUBMB Life, 69(9):689-699, 2017.
PMID- 28685938
TI - Acquired Gitelman syndrome in a primary Sjogren syndrome patient with a SLC12A3
heterozygous mutation: A case report and literature review.
AB - Acquired Gitelman's syndrome (GS) associated with Sjogren syndrome (SS) is rare.
A 50-year-old woman was admitted to our department because of nausea, acratia and
sicca complex. Laboratory tests after admission showed renal failure,
hypokalaemia, metabolic alkalosis, hypomagnesaemia and hypocalciuria, all of
which met the diagnostic criteria for GS. Diagnostic evaluation identified
primary SS as the cause of the acquired GS. Light microscopy of the renal tissue
from the patient showed severe membranoproliferative glomerunephritis and
tubulointerstitial nephritis. Immunohistochemical staining of the renal tissue
showed the absence of sodium-chloride co-transporter (NCCT) in distal convoluted
tubules. Genetic analysis of chromosomal DNA extracted from the patient's
peripheral blood showed SLC12A3 gene heterozygous mutation. The reported case was
comprehensively analyzed on the basis of the clinical features, and laboratory,
pathological and genetic test findings. The patient has achieved a complete
remission after meticulous care and appropriate treatment.
PMID- 28685939
TI - A Case of Pulmonary Mucormycosis in a Renal Transplant Recipient.
PMID- 28685940
TI - PKD1/TSC2 contiguous gene deletion syndrome.
PMID- 28685941
TI - Oxalate nephropathy presenting in exocrine pancreatic insufficiency.
PMID- 28685942
TI - Long term follow up of kidney donors with asymptomatic renal stones.
AB - Patients with asymptomatic kidney stones have a high rate of progression to
becoming symptomatic kidney stones when followed for several years. Small kidney
stones are often found incidentally on imaging when evaluating patients for
kidney donation, and there is a concern that after nephrectomy, the donor may
become symptomatic and incur damage to the remaining kidney. We reviewed kidney
donors at our institution with asymptomatic stones and surveyed them several
years after donation to see if the stones became clinically active.
PMID- 28685943
TI - Editorial: RRT in South Africa - and the relevance of Registries.
PMID- 28685944
TI - What can the treatment of Parkinson's disease learn from dementia care; applying
a bio-psycho-social approach to Parkinson's disease.
AB - BACKGROUND: Within contemporary medical practice, Parkinson's disease (PD) is
treated using a biomedical, neurological approach, which although bringing
numerous benefits can struggle to engage with how people with PD experience the
disease. A bio-psycho-social approach has not yet been established in PD;
however, bio-psycho-social approaches adopted within dementia care practice could
bring significant benefit to PD care. METHODS: This paper summarises existing bio
psycho-social models of dementia care and explores how these models could also
usefully be applied to care for PD. Specifically, this paper adapts the bio
psycho-social model for dementia developed by Spector and Orrell (), to suggest a
bio-psycho-social model, which could be used to inform routine care in PD.
RESULTS: Drawing on the biopsychosocial model of Dementia put forward by Spector
and Orrell (), this paper explores the application of a bio-psycho-social model
of PD. This model conceptualises PD as a trajectory, in which several
interrelated fixed and tractable factors influence both PD's symptomology and the
various biological and psychosocial challenges individuals will face as their
disease progresses. Using an individual case study, this paper then illustrates
how such a model can assist clinicians in identifying suitable interventions for
people living with PD. CONCLUSION: This model concludes by discussing how a bio
psycho-social model could be used as a tool in PD's routine care. The model also
encourages the development of a theoretical and practical framework for the
future development of the role of the PD specialist nurse within routine
practice. IMPLICATIONS FOR PRACTICE: A biopsychosocial approach to Parkinson's
Disease provides an opportunity to move towards a holistic model of care practice
which addresses a wider range of factors affecting people living with PD. The
paper puts forward a framework through which PD care practice can move towards a
biopsychosocial perspective. PD specialist nurses are particularly well placed to
adopt such a model within routine clinical practice, and should therefore be
encouraged within PD services.
PMID- 28685946
TI - Comparison of gastrointestinal parasite communities in vervet monkeys.
AB - Globally, habitat degradation is accelerating, especially in the tropics. Changes
to interface habitats can increase environmental overlap among nonhuman primates,
people, and domestic animals and change stress levels in wildlife, leading to
changes in their risk of parasite infections. However, the direction and
consequences of these changes are unclear, since animals may benefit by
exploiting human resources (e.g., improving nutritional health by eating
nutritious crops) and decreasing susceptibility to infection, or interactions
with humans may lead to chronic stress and increased susceptibility to infection.
Vervet monkeys are an excellent model to understand parasitic disease
transmission because of their tolerance to anthropogenic disturbance. Here we
quantify the gastrointestinal parasites of a group of vervet monkeys (Chlorocebus
aethiops) near Lake Nabugabo, Uganda, that frequently overlaps with people in
their use of a highly modified environment. We compare the parasites found in
this population to seven other sites where vervet monkey gastrointestinal
parasites have been identified. The vervets of Lake Nabugabo have the greatest
richness of parasites documented to date. We discuss how this may reflect
differences in sampling intensity or differences in the types of habitat where
vervet parasites have been sampled.
PMID- 28685945
TI - Evolutionary changes of Hox genes and relevant regulatory factors provide novel
insights into mammalian morphological modifications.
AB - The diversity of body plans of mammals accelerates the innovation of lifestyles
and the extensive adaptation to different habitats, including terrestrial, aerial
and aquatic habitats. However, the genetic basis of those phenotypic
modifications, which have occurred during mammalian evolution, remains poorly
explored. In the present study, we synthetically surveyed the evolutionary
pattern of Hox clusters that played a powerful role in the morphogenesis along
the head-tail axis of animal embryos and the main regulatory factors (Mll, Bmi1
and E2f6) that control the expression of Hox genes. A deflected density of
repetitive elements and lineage-specific radical mutations of Mll have been
determined in marine mammals with morphological changes, suggesting that
evolutionary changes may alter Hox gene expression in these lineages, leading to
the morphological modification of these lineages. Although no positive selection
was detected at certain ancestor nodes of lineages, the increased omega values of
Hox genes implied the relaxation of functional constraints of these genes during
the mammalian evolutionary process. More importantly, 49 positively-selected
sites were identified in mammalian lineages with phenotypic modifications,
indicating adaptive evolution acting on Hox genes and regulatory factors. In
addition, 3 parallel amino acid substitutions in some Hox genes were examined in
marine mammals, which might be responsible for their streamlined body.
PMID- 28685947
TI - Drawing on antiracist approaches toward a critical antidiscriminatory pedagogy
for nursing.
AB - Although nursing has a unique contribution to advancing social justice in health
care practices and education, and although social justice has been claimed as a
core value of nursing, there is little guidance regarding how to enact social
justice in nursing practice and education. In this paper, we propose a critical
antidiscriminatory pedagogy (CADP) for nursing as a promising path in this
direction. We argue that because discrimination is inherent to the production and
maintenance of inequities and injustices, adopting a CADP offers opportunities
for students and practicing nurses to develop their capacity to counteract racism
and other forms of individual and systemic discrimination in health care, and
thus promote social justice. The CADP we propose has the following features: it
is grounded in a critical intersectional perspective of discrimination, it aims
at fostering transformative learning, and it involves a praxis-oriented critical
consciousness. A CADP challenges the liberal individualist paradigm that
dominates much of western-based health care, and the culturalist and racializing
processes prevalent in nursing education. It also situates nursing practice as
responsive to health inequities. Thus, a CADP is a promising way to translate
social justice into nursing practice and education through transformative
learning.
PMID- 28685949
TI - Traditional oral health beliefs and practices of Bulang people in Yunnan, China.
AB - AIM: The aim of the present study was to explore traditional oral health beliefs
among the Bulang ethnic minority group in China. METHODS: Eighteen village
leaders, chiefs, elders, and seniors in Yunnan, China were assigned to three
focus groups for discussion of traditional oral health beliefs. The discussions
were led by a facilitator. Transcripts were made, and data were extracted.
RESULTS: The focus group discussions on traditional oral health beliefs addressed
three themes: (a) the perception of oral health; (b) the impact of healthy teeth
(oral health), in that healthy teeth essentially have an impact on physical
health, emotions, and social status; and (c) toothache management, which was
regarded as tooth decay (dental caries). Blackening teeth was a pain relief
method. Blackened teeth were reported to be part of ethnic identity, and
considered esthetically pleasing. It also indicated the marital status of women.
CONCLUSION: Some Bulang people believed that healthy dentition has no spacing,
pain, or functioning problems. Well-aligned dentition was associated with higher
social status. Toothaches were considered to be caused by tooth worms. Consulting
a monk was another way to manage a toothache. Tooth blackening was considered
traditional, and effective for caries prevention.
PMID- 28685948
TI - Role of zoledronic acid in oncolytic virotherapy: Promotion of antitumor effect
and prevention of bone destruction.
AB - Osteosarcoma is an aggressive malignant bone tumor that causes bone destruction.
Although tumor-specific replicating oncolytic adenovirus OBP-301 induces an
antitumor effect in an osteosarcoma tumor, it cannot prevent bone destruction.
Zoledronic acid (ZOL) is a clinically available agent that inhibits bone
destruction. In this study, we investigated the potential of combination therapy
with OBP-301 and ZOL against osteosarcomas with bone destruction. The antitumor
activity of OBP-301 and ZOL in monotherapy or combination therapy was assessed
using three human osteosarcoma cell lines (143B, MNNG/HOS, SaOS-2). The cytotoxic
effect of OBP-301 and/or ZOL was measured by assay of cell apoptosis. The effect
of OBP-301 and ZOL on osteoclast activation was investigated. The potential of
combination therapy against tumor growth and bone destruction was analyzed using
an orthotopic 143B osteosarcoma xenograft tumor model. OBP-301 and ZOL decreased
the viability of human osteosarcoma cells. Combination therapy with OBP-301 and
ZOL displayed a synergistic antitumor effect, in which OBP-301 promoted apoptosis
through suppression of anti-apoptotic myeloid cell leukemia 1 (MCL1). Combination
therapy significantly inhibited tumor-mediated osteoclast activation, tumor
growth and bone destruction compared to monotherapy. These results suggest that
combination therapy of OBP-301 and ZOL suppresses osteosarcoma progression via
suppression of MCL1 and osteoclast activation.
PMID- 28685950
TI - Ruthenium-Catalyzed Azide-Thioalkyne Cycloadditions in Aqueous Media: A Mild,
Orthogonal, and Biocompatible Chemical Ligation.
AB - The development of efficient metal-promoted bioorthogonal ligations remains as a
major scientific challenge. Demonstrated herein is that azides undergo efficient
and regioselective room-temperature annulations with thioalkynes in aqueous
milieu when treated with catalytic amounts of a suitable ruthenium complex. The
reaction is compatible with different biomolecules, and can be carried out in
complex aqueous mixtures such as phosphate buffered saline, cell lysates, fetal
bovine serum, and even living bacteria (E. coli). Importantly, the reaction is
mutually compatible with the classical CuAAC.
PMID- 28685951
TI - Gender differences in the correlates of loneliness among Japanese persons aged 50
70.
AB - OBJECTIVE: This study aimed to explore gender differences in the correlates of
loneliness among Japanese persons aged 50-70. METHODS: Logistic regression models
were estimated on cross-sectional Japanese Generations and Gender Survey data of
4057 persons aged 50-70. Loneliness was measured as having a score of 2 or higher
on the shortened De Jong Gierveld loneliness scale. RESULTS: For more than half
of the respondents, De Jong Gierveld loneliness scores exceeded the threshold of
2. Loneliness was more prevalent among men than among women. Living without a
spouse or partner was more strongly associated with loneliness for men than for
women. Childlessness was more strongly associated with loneliness for women than
for men. CONCLUSION: A large proportion of Japanese people between 50 and 70,
particularly men, are lonely. Programs aimed at reducing loneliness should
acknowledge that antecedents of loneliness differ between women and men.
PMID- 28685952
TI - A dual discrimination mode for improved specificity towards let-7a detection via
a single-base mutated padlock probe-based exponential rolling circle
amplification.
AB - MicroRNA (miRNA) family members are usually highly homologous sequences, and it
is a challenging task to selectively detect one miRNA member from other family
members in medical diagnosis. Here, we describe the design of a dual
discrimination mode for improved specificity towards let-7a detection over the
other members of the let-7 family, in which an intentional base mutation was
introduced into the padlock probe of an exponential rolling circle amplification.
The inherent discrimination power of the padlock probe and the introduced base
mutation constituted a dual discrimination mode, which provided enhanced
specificity for let-7a, even over single-base mismatched family sequences.
Furthermore, the assay enabled the quantitative detection of let-7a in a dynamic
range from 200 amol to 100 fmol. This technique has also been successfully
applied to real small RNA samples extracted from human lung cancers. For the
first time, through intentionally mutating one base on the padlock probe of the
exponential rolling circle amplification (RCA), we improved the discrimination
capability for let-7 family members, while maintaining adequate sensitivity.
Overall, this dual discrimination mode and the high amplification strategy have
the potential to be extended to other short, but highly homologous, miRNA
sequences.
PMID- 28685953
TI - Supramolecular Organization and Functional Implications of K+ Channel Clusters
in Membranes.
AB - The segregation of cellular surfaces in heterogeneous patches is considered to be
a common motif in bacteria and eukaryotes that is underpinned by the observation
of clustering and cooperative gating of signaling membrane proteins such as
receptors or channels. Such processes could represent an important cellular
strategy to shape signaling activity. Hence, structural knowledge of the
arrangement of channels or receptors in supramolecular assemblies represents a
crucial step towards a better understanding of signaling across membranes. We
herein report on the supramolecular organization of clusters of the K+ channel
KcsA in bacterial membranes, which was analyzed by a combination of DNP-enhanced
solid-state NMR experiments and MD simulations. We used solid-state NMR
spectroscopy to determine the channel-channel interface and to demonstrate the
strong correlation between channel function and clustering, which suggests a yet
unknown mechanism of communication between K+ channels.
PMID- 28685954
TI - Inter-group associations in Mongolian gerbils: Quantitative evidence from social
network analysis.
AB - Animals often interact non-randomly with conspecifics, and association
preferences can differ across life-history stages to maximize individuals'
fitness. Mongolian gerbils (Meriones unguiculatus) are a social rodent that live
in highly seasonal habitats and display seasonal fluctuations in population
density, growth rate and the size of overlapped home ranges. Nevertheless,
whether gerbils modify their social relationships at different life-history
stages remains unknown. Here, we used social network analysis to examine whether
social associations differ between the sexes and between life-history stages in a
wild population of Mongolian gerbils. We quantified social attributes at both
group level (assortativity) and individual level (social differentiation and
degree, closeness and betweenness centrality); these attributes reflect
individuals' social preferences and their potential influence on others in the
network. We found that both male and female gerbils established fewer inter-group
social connections during the food-hoarding season than during the breeding
season, revealing constraints on sociality. Similarly, during the food-hoarding
season, degree centrality and social differentiation increased significantly
whereas closeness and betweenness centrality decreased significantly. Together,
these results suggest that gerbils have relatively more partners and preferred
associations and decreased influence over others in the network during the food
hoarding season. In addition, we found no significant difference in any of the
social attribute between males and females, but there was a significant
interaction effect between sex and season on degree, closeness and betweenness
centrality. Our results demonstrate that Mongolian gerbils adjust their
association strategies to adapt to the changes of life history. Such adjustments
may balance the costs/benefits associated with survival and reproduction.
PMID- 28685955
TI - Language and motor skills in siblings of children with autism spectrum disorder:
A meta-analytic review.
AB - : Children with autism spectrum disorder (ASD) show significant linguistic and
motor impairments compared to children with typical development (TD). Findings
from studies of siblings of children with ASD show similarities to conclusions
from studies of children with ASD. The current meta-analysis reviewed studies
reporting linguistic and/or motor skills in siblings of children with ASD
compared to siblings of children with TD. Thirty-four studies published between
1994 and 2016 met all inclusion criteria. We compared three different age groups
(12 months or younger, 13 to 24 months, and 25 to 36 months). At 12 months,
compared to siblings of children with TD, siblings of children with ASD had worse
receptive language (d = -.43, 95% CI [-.53, -.33]) and expressive language skills
(d = -.40, 95% CI [-.57, -.23]), and these effects were sustained at 24 and 36
months. Similar, albeit smaller differences in fine motor skills were detected at
12 months (d = -.22, 95% CI [-.39, -.04]), and these differences were larger at
36 months (d = -.36, 95% CI [-.54, -.17]). There were differences in gross motor
skills at 12 months (d = -.22, 95% CI [-.40, -.04]), but only a few studies were
available at later ages. Compared to siblings of children with TD, infants who
have siblings with ASD have worse linguistic and motor skills. These differences
are detectable as early as when infants are 12 months old and seem to be
sustained until they are 3 years old. Differences in language skills are larger
than those in motor skills, especially during the first year. Autism Res 2017,
10: 1737-1750. (c) 2017 International Society for Autism Research, Wiley
Periodicals, Inc. LAY SUMMARY: We reviewed studies reporting linguistic and/or
motor skills in siblings of children with autism spectrum disorder (ASD) compared
to those in siblings of children with typical development. The results showed
that as a group, those infants who have siblings with ASD have less advanced
linguistic and motor skills. These differences are detectable when infants are 12
months old and seem to be sustained until they are 3 years old. Differences in
language skills are larger than those in motor skills.
PMID- 28685956
TI - Cocaine Hydrochloride Structure in Solution Revealed by Three Chiroptical
Methods.
AB - Structure and flexibility of natural compounds determine their biological
activity. In the present study, electronic circular dichroism (ECD), vibrational
circular dichroism (VCD), and Raman optical activity (ROA) spectra of cocaine
hydrochloride in aqueous solutions were measured and related to the structure
with the aid of density functional theory (DFT) computations. Additional
measurements in deuterated environment made assignment of vibrational bands
easier. The results suggest that the prevalent cocaine conformation in solution
differs from that adopted in hydrochloride crystal. The spectroscopic results and
computational analysis are consistent with X-ray structures of known cocaine
receptor complexes, in which the compound adopts a variety of conformations. All
three kinds of chiroptical spectra exhibited significantly greater conformational
sensitivity than unpolarized absorption or Raman scattering. The ROA technique
provided the largest number of well-resolved bands, bearing rich structural
information.
PMID- 28685957
TI - Characteristics of carotid atherosclerosis in elderly patients with type 2
diabetes at different disease course, and the intervention by statins in very
elderly patients.
AB - INTRODUCTION: Chronic complications of diabetes have become the leading cause of
death in elderly patients with diabetes. Carotid atherosclerosis, one of the
major complications, was evaluated and the effects of atorvastatin on carotid
atherosclerosis in very elderly patients with type 2 diabetes were observed.
MATERIALS AND METHODS: Patients were divided into three groups: (i) disease
course <5 years; (ii) disease course 5-10 years; (iii) disease course >10 years,
and carotid atherosclerosis was evaluated. The very elderly patients were treated
with statins, and the effect was observed. RESULTS: Carotid intima-media
thickness values, plaque instability and levels of homocysteine, cystatin, and C
reactive protein in diabetes patients were significantly higher than those in the
healthy control group, whereas levels of C-peptide and estimated glomerular
filtration rate in the patients were significantly lower. In patients with type 2
diabetes for >10 years, intima-media thickness values and plaque instability were
obviously higher than those in patients with type 2 diabetes for <5 years, while
levels of fasting C-peptide and estimated glomerular filtration rate were lower
than those in patients with type 2 diabetes for <5 years. In the very elderly
patients, after statins treatment, intima-media thickness values, levels of
homocysteine and C-reactive protein were significantly reduced, as well as the
number of unstable plaques. CONCLUSIONS: In the elderly patients with type 2
diabetes, carotid atherosclerosis-related factors increased obviously, and renal
function declined obviously, which were closely related to the disease course.
Atorvastatin significantly reduced homocysteine and C-reactive protein, and
delayed and reversed the progress of carotid atherosclerosis in very elderly
patients with type 2 diabetes.
PMID- 28685958
TI - Availability of breastfeeding peer support in the United Kingdom: A cross
sectional study.
AB - Peer support is recommended by the World Health Organization for the initiation
and continuation of breastfeeding, and this recommendation is included in United
Kingdom (U.K.) guidance. There is a lack of information about how, when, and
where breastfeeding peer support was provided in the U.K. We aimed to generate an
overview of how peer support is delivered in the U.K. and to gain an
understanding of challenges for implementation. We surveyed all U.K. infant
feeding coordinators (n = 696) who were part of U.K.-based National Infant
Feeding Networks, covering 177 National Health Service (NHS) organisations. We
received 136 responses (individual response rate 19.5%), covering 102 U.K. NHS
organisations (organisational response rate 58%). We also searched NHS
organisation websites to obtain data on the presence of breastfeeding peer
support. Breastfeeding peer support was available in 56% of areas. However,
coverage within areas was variable. The provision of training and ongoing
supervision, and peer-supporter roles, varied significantly between services.
Around one third of respondents felt that breastfeeding peer-support services
were not well integrated with NHS health services. Financial issues were commonly
reported to have a negative impact on service provision. One quarter of
respondents stated that breastfeeding peer support was not accessed by mothers
from poorer social backgrounds. Overall, there was marked variation in the
provision of peer-support services for breastfeeding in the U.K. A more robust
evidence base is urgently needed to inform guidance on the structure and
provision of breastfeeding peer-support services.
PMID- 28685959
TI - Targeting cholesterol transport in circulating melanoma cells to inhibit
metastasis.
AB - Despite recent breakthroughs in targeted- and immune-based therapies, rapid
development of drug resistance remains a hurdle for the long-term treatment of
patients with melanoma. Targeting metastatically spreading circulating tumor
cells (CTCs) may provide an additional approach to manage melanoma. This study
investigates whether targeting cholesterol transport in melanoma CTCs can retard
metastasis development. Nanolipolee-007, the liposomal form of leelamine, reduced
melanoma metastasis in both a novel in vitro flow system mimicking the
circulating system and in experimental as well as spontaneous animal metastasis
models, irrespective of the BRAF mutational status of the CTCs. Leelamine led to
cholesterol trapping in lysosomes, which subsequently shut down receptor-mediated
endocytosis, endosome trafficking, and inhibited the major oncogenic signaling
cascades important for survival such as the AKT pathway. As pAKT is important in
CTC survival, inhibition by targeting cholesterol metabolism led to apoptosis,
suggesting this approach might be particularly effective for those CTCs having
high levels of pAKT to aid survival in the circulation system.
PMID- 28685960
TI - Platelet-Derived Mitochondria Display Embryonic Stem Cell Markers and Improve
Pancreatic Islet beta-cell Function in Humans.
AB - Diabetes is a major global health issue and the number of individuals with type 1
diabetes (T1D) and type 2 diabetes (T2D) increases annually across multiple
populations. Research to develop a cure must overcome multiple immune
dysfunctions and the shortage of pancreatic islet beta cells, but these
challenges have proven intractable despite intensive research effort more than
the past decades. Stem Cell Educator (SCE) therapy-which uses only autologous
blood immune cells that are externally exposed to cord blood stem cells adhering
to the SCE device, has previously been proven safe and effective in Chinese and
Spanish subjects for the improvement of T1D, T2D, and other autoimmune diseases.
Here, 4-year follow-up studies demonstrated the long-term safety and clinical
efficacy of SCE therapy for the treatment of T1D and T2D. Mechanistic studies
found that the nature of platelets was modulated in diabetic subjects after
receiving SCE therapy. Platelets and their released mitochondria display immune
tolerance-associated markers that can modulate the proliferation and function of
immune cells. Notably, platelets also expressed embryonic stem cell- and
pancreatic islet beta-cell-associated markers that are encoded by mitochondrial
DNA. Using freshly-isolated human pancreatic islets, ex vivo studies established
that platelet-releasing mitochondria can migrate to pancreatic islets and be
taken up by islet beta cells, leading to the proliferation and enhancement of
islet beta-cell functions. These findings reveal new mechanisms underlying SCE
therapy and open up new avenues to improve the treatment of diabetes in clinics.
Stem Cells Translational Medicine 2017;6:1684-1697.
PMID- 28685961
TI - A novel colorimetric fluorescence sensor for Fe3+ based on quinoline Schiff base.
AB - A novel fluorescent sensor bearing a quinoline and an anisidine moiety has been
developed for highly selective detection of Fe3+ , which shows photo-induced
electron transfer (PET) behavior induced by Fe3+ . Binding of Fe3+ to the sensor
induced the electron of C = N group transfer from quinoline to iron, the result
exhibits fluorescent enhancement. With the features of easy synthesis, simple
structural skeleton and excellent sensing ability, the newly synthesized
chemosensor also applied as a highly selective fluorescent probe in complex
samples containing various competitive metal ions. The probe could fulfill
various needs in biological and environmental fields.
PMID- 28685962
TI - Flow Asymmetric Propargylation: Development of Continuous Processes for the
Preparation of a Chiral beta-Amino Alcohol.
AB - The development of a flow chemistry process for asymmetric propargylation using
allene gas as a reagent is reported. The connected continuous process of allene
dissolution, lithiation, Li-Zn transmetallation, and asymmetric propargylation
provides homopropargyl beta-amino alcohol 1 with high regio- and
diastereoselectivity in high yield. This flow process enables practical use of an
unstable allenyllithium intermediate. The process uses the commercially available
and recyclable (1S,2R)-N-pyrrolidinyl norephedrine as a ligand to promote the
highly diastereoselective (32:1) propargylation. Judicious selection of mixers
based on the chemistry requirement and real-time monitoring of the process using
process analytical technology (PAT) enabled stable and scalable flow chemistry
runs.
PMID- 28685963
TI - Associations between birthweight and overweight and obesity in school-age
children.
AB - BACKGROUND: Relationships between birthweight and future obesity risk remain
unclear. OBJECTIVE: To assess associations between birthweight and later obesity
in a nationally representative cohort of early school-aged children. METHODS: We
used linear and logistic regression to evaluate 10 186 term- or preterm children
in the Early Childhood Longitudinal Study-Kindergarten Cohort 2011 for
relationships between birthweight and later obesity and change in BMI z-score
from kindergarten-to-second grade. All analyses were adjusted for sex,
race/ethnicity, parental education and household income. RESULTS: Compared to
children born normal birthweight (NBW), high birthweight (HBW) term children and
large-for-gestational-age (LGA) preterm children had significantly greater BMI z
scores from kindergarten-to-second grade (p < 0.001). Term children born HBW had
higher odds of obesity by kindergarten (adjusted odds ratios [aOR] 1.91, p <
0.0001). Among preterm children, odds of obesity was higher among LGA children
starting in first grade (aOR 2.34, p < 0.05) and among small-for-gestational age
children in second grade (aOR 2.26, p < 0.05). Compared to NBW children, HBW
children had greater change in BMI z-score between kindergarten-first grade (p <
0.01). CONCLUSIONS: High birthweight term and LGA preterm children had increased
adjusted odds of obesity in school-age compared to their NBW counterparts.
Physicians may provide counselling early in life for families of large infants to
help prevent future obesity.
PMID- 28685964
TI - hsa_circ_0013958: a circular RNA and potential novel biomarker for lung
adenocarcinoma.
AB - Circular RNAs (circRNAs) are associated with cancer progression and metastasis,
although little is known about their role in lung adenocarcinoma (LAC). In the
present study, microarrays were first used to screen for tumour-specific circRNA
candidates in LAC tissue. Thirty-nine circRNAs were found to be up-regulated and
20 were down-regulated (fold change > 2.0). Among them, hsa_circ_0013958 was
further confirmed to be up-regulated in all of the LAC tissues, cells and plasma.
In addition, hsa_circ_0013958 levels were associated with TNM stage (P = 0.009)
and lymphatic metastasis (P = 0.006). The area under the receiver operating
characteristic curve was 0.815 (95% confidence interval = 0.727-0.903; P <
0.001). In addition, to further illustrate the bioactivities of hsa_circ_0013958
in LAC, siRNA-mediated inhibition of hsa_circ_0013958 was performed in vitro. The
results showed that hsa_circ_0013958 promoted cell proliferation and invasion and
inhibited cell apoptosis in LAC. Moreover, hsa_circ_0013958 was identified as a
sponge of miR-134, and thus it up-regulated oncogenic cyclin D1, which plays a
pivotal role in the development of non-small cell lung cancer. In conclusion, our
results suggested that hsa_circ_0013958 could be used as a potential non-invasive
biomarker for the early detection and screening of LAC.
PMID- 28685965
TI - High-Spatial Resolution Mass Spectrometry Imaging: Toward Single Cell
Metabolomics in Plant Tissues.
AB - Mass spectrometry imaging (MSI) is a powerful tool that has advanced our
understanding of complex biological processes by enabling unprecedented details
of metabolic biology to be uncovered. Through the use of high-spatial resolution
MSI, metabolite localizations can be obtained with high precision. Here we
describe our recent progress to enhance the spatial resolution of matrix-assisted
laser desorption/ionization (MALDI) MSI from ~50 MUm with the commercial
configuration to ~5 MUm. Additionally, we describe our efforts to develop a
'multiplex MSI' data acquisition method to allow more chemical information to be
obtained on a single tissue in a single instrument run, and the development of
new matrices to improve the ionization efficiency for a variety of small molecule
metabolites. In combination, these contributions, along with the efforts of
others, will bring MSI experiments closer to achieving metabolomic scale.
PMID- 28685966
TI - The impact of a Web-based educational program on the recognition and management
of deteriorating patients.
AB - AIMS AND OBJECTIVES: To evaluate the effectiveness of a Web-based educational
program to enhance enrolled nurses' knowledge and skills in the recognition and
management of deteriorating patients. BACKGROUND: Ward nurses of different skill
levels play a pivotal role in detecting and responding to deteriorating patients.
A skill mix of registered nurses, enrolled nurses, licensed practical nurses or
healthcare assistants is often employed for the provision of nursing care in
acute settings. Non-registered nurses frequently perform bedside care and are in
the best position to detect deteriorating patients and initiate immediate
actions, including commanding the attention of registered nurses. Education is
needed to improve the knowledge and skills of these nurses. DESIGN: A randomised
controlled trial with a pretest-post-test design. METHODS: The sample included
enrolled nurses from an acute care tertiary hospital. Following a baseline
evaluation, the experimental group received a Web-based educational intervention.
Pre-post assessment of skills and knowledge was performed with a simulated
scenario and a knowledge questionnaire. Sixty-four nurses completed the entire
study. RESULTS: Following the intervention, participants from the experimental
group were significantly more likely than those in the control group to monitor
the patient's respiratory and pulse rates. In addition, they had significantly
higher post-test mean scores for knowledge and skills in assessing and managing
clinical deterioration and reporting deterioration. CONCLUSION: The Web-based
educational intervention significantly improved enrolled nurses' knowledge and
skills in the recognition and management of a deteriorating patient in a
simulated setting. RELEVANCE TO CLINICAL PRACTICE: Ease of access to the Web
based platform contributed to the feasibility and acceptability of this study,
which has the potential to positively impact patient safety.
PMID- 28685967
TI - Rapid solid-phase extraction coupled with GC-MS method for the determination of
venlafaxine in rat plasma: Application to the drug-drug pharmacokinetic
interaction study of venlafaxine combined with fluoxetine.
AB - A rapid and sensitive gas chromatography with mass spectrometry method for the
determination of venlafaxine in rat plasma has been developed and applied to a
drug-drug interaction study of fluoxetine on pharmacokinetics of venlafaxine in
rats. Rat plasma was spiked with 2% aqueous ammonia before subjected to
preactivated C18 solid-phase extraction columns and eluted with methanol. No
endogenous interferences were observed under optimal condition. The calibration
curve was linear (R2 = 0.9994) in the range of 10-1000 ng/mL. The quantification
limit of venlafaxine in rat plasma was 10 ng/mL. The accuracy was in the range of
85-110%, and the extraction recovery was no less than 50%. Both the intra- and
interday precision were 5.0-10.7%. The concentration-time curve showed that
plasma concentrations of the coadministration group (group B) were higher than
that of single dose group (group A). Both values of Cmax (0.069 mg/L) and AUC0
>infinity (0.291 mg h/L) in group B were statistically greater than that of Cmax
(0.046 mg/L) and AUC0->infinity (0.181 mg.h/L) in group A (P < 0.05). The results
indicated that a significant effect of fluoxetine was shown on the
pharmacokinetics of venlafaxine, suggesting that drug-drug interactions are of
concern for the treatment of depression with the combined use of venlafaxine and
fluoxetine.
PMID- 28685968
TI - Prevalence of and risk factors for diabetic ketosis in Chinese diabetic patients
with random blood glucose levels >13.9 mmol/L: Results from the CHina study in
prEvalence of diabetiC Ketosis (CHECK) study.
AB - BACKGROUND: The aim of the present study was to investigate the prevalence of
diabetic ketosis (DK) and its risk factors in Chinese diabetes patients with
severe hyperglycemia. METHODS: The present multicenter cross-sectional study was
performed on patients aged >16 years with diabetes mellitus (DM) and random blood
glucose levels >13.9 mmol/L (>250 mg/dL). Blood ketones (beta-hydroxybutyric
acid) and urinary ketones (acetoacetic acid) were measured and information on
patient demographic and clinical characteristics was collected. RESULTS: Of 1235
patients enrolled in the study (93 with type 1 DM [T1DM]), 1142 with type 2 DM
[T2DM]), 242 (19.6%) had DK (blood ketone levels >=0.6 mmol/L). Proportionately,
DK was more frequent and more severe in patients with T1DM than T2DM (55.9% vs
16.6%, respectively), but in absolute terms occurred in more patients with T2DM
(52 vs 190). In patients with blood ketone levels >=3 mmol/L, the cut-off point
of blood glucose levels was 19.05 mmol/L. Risk factors significantly associated
with higher blood ketone levels in T2DM included younger age, a shorter duration
of diabetes, and not using antidiabetic medication within 12 months prior to the
hyperglycemic episode. CONCLUSIONS: The prevalence of DK is lower in patients
with T2DM than T1DM, but the number of patients with DK is higher for those with
T2DM because of more T2DM patients in China. Patients with T2DM who have a
younger age, shorter duration of diabetes, and a lack of antidiabetic treatment
will suffer from DK more often than older patients with longer T2DM duration and
receiving antidiabetic treatment.
PMID- 28685969
TI - The Cytochrome P450 3A4 has three Major Conformations: New Clues to Drug
Recognition by this Promiscuous Enzyme.
AB - We computed the channels of the 3A4 isoform of the cytochrome P450 3A4 (CYP) on
the basis of 24 crystal structures extracted from the Protein Data Bank (PDB). We
identified three major conformations (denoted C, O1 and O2) using an enhanced
version of the CCCPP software that we developed for the present work, while only
two conformations (C and O2 ) are considered in the literature. We established
the flowchart of definition of these three conformations in function of the
structural and physicochemical parameters of the ligand. The channels are
characterized with qualitative and quantitative parameters, and not only with
their surrounding secondary structures as it is usually done in the literature.
PMID- 28685970
TI - Invariant natural killer cells change after an oral allergy desensitization
protocol for cow's milk.
AB - BACKGROUND: Cow milk (CM) allergy (CMA) affects up to 3% of the paediatric
population and recent data suggest that only about 50% will outgrow by age 8.
Oral immunotherapy (OIT) is a type of immune-modulating treatment that is able to
induce desensitization to food allergens, to increase tolerance threshold, to
reduce the risk of anaphylaxis, and to improve the patient's quality of life. The
examination of the immunological changes observed during the establishment of
food allergy (FA) desensitization in FA patients is a window into the
pathogenesis of food allergy and food tolerance development. In this pathway, we
have previously found that invariant natural killer T cells (iNKTs) are involved
in CM allergy sensitization and now examine their role in OIT. METHODS: In this
study, 10 of the 11 children with CM induced anaphylaxis enrolled in a CMA OIT
clinical trial and completed the protocol. Peripheral blood iNKTs were
quantitatively and qualitatively via flow cytometry characterized ex vivo and
after culture with milk lipids before and after completing the OIT protocol.
RESULTS: After completing OIT for CM, children were able to reintroduce CM in
their diet. For the first time, we demonstrated that OIT induced a significant
increase in the peripheral blood iNKT, as well as their switch from a T helper
(Th-2; ie IL-4, IL-13) to Th-1 (ie IFN-gamma) cytokine profile. CONCLUSIONS AND
CLINICAL RELEVANCE: This study confirms the efficacy and safety of CM-OIT as well
as the role of iNKT cells in CM allergy.
PMID- 28685971
TI - Self-compassion moderates the predictive effects of implicit cognitions on
subjective well-being.
AB - This study examined whether self-compassion may regulate the effects of implicit
cognitions (automatic and preconscious responses) on the subjective well-being of
Australian adults (N = 132). As hypothesized, self-compassion moderated the
predictive effects of 2 implicit cognitions (positive attention bias and implicit
self-esteem) on 2 indicators of subjective well-being (life satisfaction and
depressive symptoms). Low implicit self-esteem and weak positive attention bias
predicted more depressive symptoms and lower life satisfaction only for
participants who were low in self-compassion. These results extend previous
research knowledge by indicating that self-compassion may not only buffer the
impact of explicit (deliberate and conscious) cognitive processes on well-being
but may also regulate the effects of preconscious cognitive processes on mental
health outcomes. Theoretical and treatment implications are discussed.
PMID- 28685972
TI - KIR2DS5 allotypes that recognize the C2 epitope of HLA-C are common among
Africans and absent from Europeans.
AB - INTRODUCTION: KIR2DS5 is an activating human NK cell receptor of lineage III KIR.
These include both inhibitory KIR2DL1, 2 and 3 and activating KIR2DS1 that
recognize either the C1 or C2 epitope of HLA-C. In Europeans KIR2DS5 is
essentially monomorphic, with KIR2DS5*002 being predominant. Pioneering
investigations showed that KIR2DS5*002 has activating potential, but cannot
recognize HLA-A, -B, or -C. Subsequent studies have shown that KIR2DS5 is highly
polymorphic in Africans, and that KIR2DS5*006 protects pregnant Ugandan women
from preeclampsia. Because inhibitory C2-specific KIR2DL1 correlates with
preeclampsia, whereas activating C2-specific KIR2DS1 protects, this association
pointed to KIR2DS5*006 being an activating C2-specific receptor. To test this
hypothesis we made KIR-Fc fusion proteins from all ten KIR2DS5 allotypes and
tested their binding to a representative set of HLA-A, -B and -C allotypes.
RESULTS: Six African-specific KIR2DS5 bound to C2+ HLA-C but not to other HLA
class I. Their avidity for C2 is ~20% that of C2-specific KIR2DL1 and ~40% that
of C2-specific KIR2DS1. Among the African C2 receptors is KIR2DS5*006, which
protected a cohort of pregnant Ugandans from pre-eclampsia. Three African KIR2DS5
allotypes and KIR2DS5*002, bound no HLA-A, -B or -C. As a group the C2-binding
KIR2DS5 allotypes protect against pre-eclampsia compared to the non-binding
KIR2DS5 allotypes. Natural substitutions that contribute to loss or reduction of
C2 receptor function are at positions 127, 158, and 176 in the D2 domain.
CONCLUSIONS: KIR2DS5*005 has the KIR2DS5 consensus sequence, is the only allele
found at both centromeric and telomeric locations of KIR2DS5, and is likely the
common ancestor of all KIR2DS5 alleles. That KIR2DS5*005 has C2 receptor
activity, points to KIR2DS5*002, and other allotypes lacking C2 receptor
function, being products of attenuation, a characteristic feature of most KIR B
haplotype genes. Alleles encoding attenuated and active KIR2DS5 are present in
both centromeric and telomeric locations.
PMID- 28685974
TI - Thermosensitive Triterpenoid-Appended Polymers with Broad Temperature Tunability
Regulated by Host-Guest Chemistry.
AB - Thermoresponsive water-soluble polymers are of great importance since they
typically show a lower critical solution temperature (LCST) in aqueous media. In
this research, the LCST change in broad temperature ranges of copolymers composed
of natural glycyrrhetinic acid (GA)-based methacrylate and N,N'
dimethylacrylamides (DMAs) was investigated as a function of the concentration
and the content of GA pendants. By complexation of GA pendants with beta
cyclodextrin (beta-CD), a side-chain polypseudorotaxane was obtained, which
exhibited a significant increase in the LCST of copolymers. Moreover, the
precisely reversible control of the LCST behavior was realized through adding a
competing guest molecule, sodium 1-admantylcarboxylate. This work illustrates a
simple and effective approach to endow water-soluble polymers with broad
temperature tunability and helps us further understand the effect of a
biocompatible host-guest complementary beta-CD/GA pair on the thermoresponsive
process.
PMID- 28685973
TI - Efficacy and tolerability of the new autoinjected suspension of exenatide once
weekly versus exenatide twice daily in patients with type 2 diabetes.
AB - AIMS: To simplify administration of aqueous exenatide once weekly, which requires
reconstitution, the exenatide microspheres have been reformulated in a ready-to
use autoinjector with a Miglyol diluent (exenatide QWS-AI). This study compared
the efficacy and safety of exenatide QWS-AI with the first-in-class glucagon-like
peptide-1 receptor agonist exenatide twice daily (BID). MATERIALS AND METHODS:
This randomized, open-label, controlled study in patients with type 2 diabetes
using diet and exercise or taking stable oral glucose-lowering medication
randomized patients 3:2 to either exenatide QWS-AI (2 mg) or exenatide BID (10
MUg) for 28 weeks. The primary outcome was the 28-week change in glycated
haemoglobin (HbA1c). A subset of patients completed a standardized meal test for
postprandial and pharmacokinetic assessments. RESULTS: A total of 375 patients
(mean HbA1c, 8.5% [69 mmol/mol]; body mass index, 33.2 kg/m2 ; diabetes duration,
8.5 years) received either exenatide QWS-AI (n = 229) or exenatide BID (n = 146);
HbA1c was reduced by -1.4% and -1.0%, respectively (least-squares mean
difference, -0.37%; P = .0072). More patients achieved HbA1c <7.0% with exenatide
QWS-AI (49.3%) than with exenatide BID (43.2%; P = .225). Body weight was reduced
in both groups (P = .37 for difference). Gastrointestinal adverse events (AEs)
were reported in 22.7% (exenatide QWS-AI) and 35.6% (exenatide BID) of patients;
fewer patients in the exenatide QWS-AI group withdrew because of AEs than in the
exenatide BID group. Minor hypoglycaemia occurred most often with concomitant
sulfonylurea use. CONCLUSIONS: Exenatide QWS-AI was associated with a greater
reduction in HbA1c, similar weight loss and a favorable gastrointestinal AE
profile compared with exenatide BID.
PMID- 28685975
TI - Lasing transition at 1.06 MUm emission in Nd3+ -doped borate-based tellurium
calcium zinc niobium oxide glasses for high-power solid-state lasers.
AB - The spectroscopic properties of Tellurium Calcium Zinc Niobium oxide Borate
(TCZNB) glasses of composition (in mol%) 10TeO2 + 15CaO + 5ZnO + 10 Nb2 O5 +
(60 - x)B2 O3 + Nd2 O3 (x = 0.1, 0.5, 1.0 or 1.5 mol%) have been investigated
experimentally. The three phenomenological intensity parameters Omega2 , Omega4,
Omega6 have been calculated using the Judd-Ofelt theory and in turn radiative
properties such as radiative transition probabilities, emission cross-sections,
branching ratios and radiative lifetimes have been estimated. The trend found in
the JO intensity parameter is Omega2 > Omega6 > Omega4 If Omega6 > Omega4 ,
the glass system is favourable for the laser emission 4 F3/2 -> 4 I11/2 in the
infrared (IR) wavelength. The experimental values of branching ratio of 4 F3/2
> 4 I11/2 transition indicate favourable lasing action with low threshold power.
The evaluated total radiative transition probabilities (AT ), stimulated emission
cross-section (sigmae ) and gain bandwidth parameters (sigmae * Deltalambdap )
were compared with earlier reports. An energy level analysis has been carried out
considering the experimental energy positions of the absorption and emission
bands.
PMID- 28685976
TI - Mandibular division trigeminal nerve injuries following primary endodontic
treatment. A case series.
AB - The aim of this study is to report a series of patients with mandibular division
trigeminal nerve (V3 ) injuries secondary to endodontic treatment, evaluate
presentation characteristics and identify prevention strategies. This article
describes a retrospective review of patients referred to a tertiary clinic 2007
2015 with V3 injury following endodontic treatment. The sample included 12 male
and 16 female patients with a mean age of 41.5 years. Sixteen cases presented
following endodontic treatment of the first and second molar, premolar teeth in
eight cases and canine in two cases. Fifteen patients reported immediate post
operative symptoms, in eleven cases there was a 24-48 h asymptomatic period. The
average referral delay was 23.1 months. Twenty patients had permanent neuropathy.
Four patients experienced resolution of symptoms within 8 weeks. V3 injury
following endodontic treatment is rare but can result in permanent neuropathy and
functional impairment. This can be avoided through comprehensive pre-operative
radiographic examination, identification and referral of high-risk cases.
PMID- 28685977
TI - The post-therapeutic effect of rapamycin in mild traumatic brain-injured rats
ensuing in the upregulation of autophagy and mitophagy.
AB - Mild traumatic brain injury (mTBI), common in juveniles, has been reported to be
caused by sports-related concussion. Many young children may suffer from post
concussion syndrome. mTBI, in early stages of life, could play a part in neuron
apoptosis and degeneration, cognitive and motor coordination impairment, as well
as dementia. Our study was aimed at further investigating the post-therapeutic
efficacy of rapamycin in the recuperation of mTBI while at the same time
investigating the metamorphosis in both autophagy and mitophagy in mTBI. We
created a weight-drop rat mTBI model with the administration of rapamycin at 4 h
after every mTBI. Behavioral tests of beam walking and open field task indicated
the expected improvement of cognitive and motor coordination functions. Both
Western blot and immunofluorescence examinations revealed increased Beclin-1 and
PINK1 in the treated rats as well as reduction of caspase-3 and cytochrome C (Cyt
C). More so, the TUNEL staining evidenced curtailment of apoptotic cells
following treatment with rapamycin. The upregulation of Beclin-1 and PINK1 and
the downregulation of caspase-3 and Cyt C extrapolate that rapamycin plays
neuroprotective as well as anti-apoptotic role via interposition of both
autophagy and mitophagy.
PMID- 28685978
TI - The viable but nonculturable state induction and genomic analyses of
Lactobacillus casei BM-LC14617, a beer-spoilage bacterium.
AB - This study aimed to investigate the viable but nonculturable (VBNC) state and
genomic features of a beer-spoilage strain, Lactobacillus caseiBM-LC14617.
Induction on the VBNC state of L. casei strain BM-LC14617 was conducted by both
low-temperature storage and continuous passage in beer, and formation of VBNC
state was detected after 196 +/- 3.3 days and 32 +/- 1.6 subcultures,
respectively. Resuscitation of VBNC cells was successfully induced by addition of
catalase, and culturable, VBNC, and resuscitated cells shared similar beer
spoilage capability. Whole genome sequencing was performed, and out of a total of
3,964 predicted genes, several potential VBNC and beer-spoilage-associated genes
were identified. L. casei is capable of entering into and resuscitating from the
VBNC state and possesses beer-spoilage capability. The genomic characterization
yield insightful elucidation of VBNC state for L. casei. This study represents
the first evidence on VBNC state induction of L. casei and beer-spoilage
capability of VBNC and resuscitated cells. Also, this is the first genomic
characterization of L. casei as a beer-spoilage bacterium. The current study may
aid in further study on L. casei and other beer-spoilage bacteria, and guide the
prevention and control of beer spoilage.
PMID- 28685979
TI - Professionalism and social media in pediatric anesthesia.
PMID- 28685980
TI - Is single-shot thoracic epidural the only aid to early discharge after pediatric
laparoscopic cholecystectomy.
PMID- 28685981
TI - Reply to Baines, David, regarding their comment 'Comment on Erb TO, von Ungern
Sternberg BS, Moll J, Frei FJ. Impact of high concentrations of sevoflurane on
laryngeal reflex responses'.
PMID- 28685982
TI - How should training in Pediatric Cardiac Anesthetic Training be undertaken-And in
what sort of centers?
PMID- 28685983
TI - Comment on Erb TO, von Ungern-Sternberg BS, Moll J, Frei FJ. Impact of high
concentrations of sevoflurane on laryngeal reflex responses.
PMID- 28685984
TI - Two infants with presumed Zika congenital syndrome presenting for exam under
general anesthesia.
PMID- 28685985
TI - Anesthesia for fetal surgery.
PMID- 28685986
TI - A case of Hirschsprung disease recognized during anesthesia induction with
nitrous oxide.
PMID- 28685987
TI - The complexities of delivering anesthesia and pediatric intensive care to a
critically Ill pediatric refugee.
PMID- 28685988
TI - Preoperative fasting in children: is there room for improvement?
PMID- 28685989
TI - Tramadol: keep calm and carry on.
PMID- 28685990
TI - Editorial.
PMID- 28685991
TI - Pyridine-Fused Bis(Norcorrole) through Hantzsch-Type Cyclization: Enhancement of
Antiaromaticity by an Aromatic Bridge.
AB - A non-catalytic condensation of NiII beta-aminonorcorrole with aryl aldehydes is
shown to produce a family of pyrromethane dimers that undergo deaminative
cyclization to yield pyridine-fused bis(norcorrole)s comprising two antiaromatic
macrocycles communicating by an aromatic moiety. The new compounds were
characterized by spectroscopic, structural, and electrochemical methods supported
by DFT calculations, all of which revealed unexpected antiaromaticity enhancement
in the fused system.
PMID- 28685992
TI - Concentration-Gradient Multichannel Flow-Stream Membrane Capacitive Deionization
Cell for High Desalination Capacity of Carbon Electrodes.
AB - We present a novel multichannel membrane flow-stream capacitive deionization (MC
MCDI) concept with two flow streams to control the environment around the
electrodes and a middle channel for water desalination. The introduction of side
channels to our new cell design allows operation in a highly saline environment,
while the feed water stream in the middle channel (conventional CDI channel) is
separated from the electrodes with anion- and cation-exchange membranes. At a
high salinity gradient between side (1000 mm) and middle (5 mm) channels, MC-MCDI
exhibited an unprecedented salt-adsorption capacity (SAC) of 56 mg g-1 in the
middle channel with charge efficiency close to unity and low energy consumption.
This excellent performance corresponds to a fourfold increase in desalination
performance compared to the state-of-the-art in a conventional CDI cell. The
enhancement originates from the enhanced specific capacitance in high-molar
saline media in agreement with the Gouy-Chapman-Stern theory and from a double
ion desorption/adsorption process of MC-MCDI through voltage operation from -1.2
to +1.2 V.
PMID- 28685993
TI - Association of single nucleotide polymorphisms in microRNAs with susceptibility
to hepatitis B virus infection and HBV-related liver complications: A study in a
Saudi Arabian population.
AB - The aim of this study was to evaluate the association of 10 SNPs in different
microRNAs (miRNAs) with susceptibility to hepatitis B virus (HBV) infection, HBV
clearance, persistence of chronic HBV infection, and progression to liver
cirrhosis and hepatocellular carcinoma (HCC). Patients were categorized into the
following groups: inactive HBV carrier, active HBV carrier, HBV-cleared subject
and cirrhosis+HCC. Samples were analysed for 10 SNPs in microRNAs using either
PCR-based genotyping or the TaqMan assay. We found that rs1358379 was associated
with susceptibility to HBV infection, HBV clearance, persistent chronic HBV
infection and liver cirrhosis+HCC. In addition, we found that rs2292832 and
rs11614913 were associated with risk of HBV infection, viral clearance and
cirrhosis+HCC, whereas rs2910164 was associated with proneness to HBV infection,
and ability to clear the virus. There was evidence of associations between
rs6505162 and HBV clearance and the development of liver disease, whereas a
single association was found between rs2289030 and HBV clearance. Similarly,
rs7372209 and rs4919510 were specifically associated with the development of HBV
induced liver complications. SNPs in miRNAs affect the susceptibility, clearance
and progression of HBV infection in Saudi Arabian patients. We found, using Gene
Ontology or pathway analyses, that these genes may contribute to the
pathophysiology of HBV infection and related liver complications. However,
differences in the association of examined SNPs with various clinical stages
indicate variations in the respective functional roles of these polymorphisms and
their miRNAs, and thus, further investigation to fully explore their therapeutic
potential is warranted.
PMID- 28685994
TI - Gibberellin-regulated protein in Japanese apricot is an allergen cross-reactive
to Pru p 7.
AB - BACKGROUND: Gibberellin-regulated protein (GRP, also known as peamaclein) was
recently identified as a new marker allergen related to systemic reactions in
peach allergy; however, its role in other fruit allergies is unknown. OBJECTIVE:
To investigate the allergenicity of Japanese apricot (JA) GRP and clarify the
clinical characteristics of JA allergy patients with GRP sensitization. METHODS:
Seven patients (two males, five females, mean age 28.0 years) diagnosed with JA
allergy based on relevant clinical history, positive skin test and/or challenge
test were enrolled. JA GRP with a molecular weight of 6896.5 Da was purified by
ion-exchange column chromatography. We performed enzyme-linked immunosorbent
assay (ELISA), IgE-immunoblotting, basophil activating tests (BATs), and skin
prick tests (SPTs) with purified JA GRP. To investigate the cross-reactivity
between JA GRP and native Pru p 7 (nPru p 7), we performed ELISA inhibition
tests. We measured specific IgE levels against apricot, peach, rPru p 1, rPru p
3, and rPru p 4 using ImmunoCAP. RESULTS: ELISA and IgE-immunoblotting using JA
GRP showed positive reactions in six (85.7%) and seven (100%) patients,
respectively. Five patients who provided informed consent for BATs and SPTs using
JA GRP had positive results. In four patients who underwent ELISA inhibition
tests using JA GRP and nPru p 7, IgE binding to one GRP inhibited binding to the
other. The positivity for specific IgE against apricot, peach, rPru p 1, rPru p
3, and rPru p 4 was 14.3%, 57.1%, 0%, 0%, and 0%, respectively. Patients
developed allergic reactions that were frequently accompanied with facial
swelling, especially of the eyelids, which was dependent on cofactors, such as
exercise. CONCLUSIONS AND CLINICAL RELEVANCE: These results indicated that GRP
might be a causative allergen of JA allergy, whose onset frequently requires a
cofactor, such as exercise, and might be cross-reactive between JAs and peaches.
PMID- 28685995
TI - Meta-analysis and critical review on the efficacy and safety of alpha-glucosidase
inhibitors in Asian and non-Asian populations.
AB - AIMS/INTRODUCTION: To evaluate the efficacy and safety of alpha-glucosidase
inhibitors (AGI) in Asian and non-Asian type 2 diabetes patients. MATERIALS AND
METHODS: Studies were identified through a literature search of MEDLINE, EMBASE
and other databases until December 2016. All statistical analyses were carried
out in Review Manager statistical software by computing the weighted mean
difference or odds ratio and 95% confidence interval. RESULTS: A total of 67
studies were included. AGI vs placebo: compared with the placebo, AGI treatment
led to a greater decrease in hemoglobin A1c (HbA1c), fasting plasma glucose and
postprandial plasma glucose. No significant difference was observed in HbA1c
change, fasting plasma glucose change, postprandial plasma glucose change or
incidence of hypoglycemia between Asian and non-Asian patients. AGI vs active
controls: in Asian patients, AGI treatment showed a lower reduction in HbA1c
compared with dipeptidyl peptidase-4 inhibitors and sulfonylurea. In non-Asian
patients, AGI treatment showed a lower reduction in HbA1c compared with
thiazolidinedione. No significant difference was observed in HbA1c change and
bodyweight change when comparing AGI with other oral hypoglycemic agents between
Asian and non-Asian patients. CONCLUSIONS: The effects of AGI treatment on
glycemic control and bodyweight reduction were superior to the placebo without an
increased incidence of hypoglycemia, but with an increased incidence of
gastrointestinal discomforts. The hypoglycemic effects of AGI were comparable
between Asian and non-Asian patients.
PMID- 28685997
TI - Calcified Curschmann's spirals and microliths in sputum smears from a case of
pulmonary alveolar microlithiasis.
PMID- 28685996
TI - Are autistic traits associated with suicidality? A test of the interpersonal
psychological theory of suicide in a non-clinical young adult sample.
AB - : Autism spectrum conditions (ASC) has recently been associated with increased
risk of suicidality. However, no studies have explored how autistic traits may
interact with current models of suicidal behavior in a non-clinical population.
The current study therefore explored how self-reported autistic traits interact
with perceived burdensomeness and thwarted belongingness in predicting suicidal
behavior, in the context of the Interpersonal-Psychological Theory of Suicide
(IPTS). 163 young adults (aged 18-30 years) completed an online survey including
measures of thwarted belonging and perceived burdensomeness (Interpersonal Needs
Questionnaire), self-reported autistic traits (Autism Spectrum Quotient), current
depression (Centre for Epidemiological Studies Depression Scale), and lifetime
suicidality (Suicide Behavior Questionnaire-Revised). Results showed that
burdensomeness and thwarted belonging significantly mediated the relationship
between autistic traits and suicidal behavior. Both depression and autistic
traits significantly predicted thwarted belonging and perceived burdensomeness.
Autistic traits did not significantly moderate the relationship between suicidal
behavior and thwarted belonging or perceived burdensomeness. Results suggest that
the IPTS provides a useful framework for understanding the influence of autistic
traits on suicidal behavior. However, the psychometric properties of these
measures need be explored in those with clinically confirmed diagnosis of ASC.
Autism Res 2017, 10: 1891-1904. (c) 2017 The Authors Autism Research published by
International Society for Autism Research and Wiley Periodicals, Inc. LAY
SUMMARY: Recent research has shown that people with high autistic traits are more
likely to attempt suicide. However, no studies have explored why. We found that
people with high autistic traits were more likely to experience feelings that
they do not belong in the world, are a burden on others, and depression, which
may increase their likelihood of attempting suicide. These results suggest that
promoting inclusion and independence in those with high autistic traits could
help prevent people attempting suicide.
PMID- 28685998
TI - Iridociliary cysts masquerading as neoplasia in cats: a morphologic review of 14
cases.
AB - OBJECTIVE: To report 14 neoplasia-free feline eyes enucleated for suspected
intraocular neoplasia containing only iridociliary cysts. To analyze clinical
findings that may have led veterinarians to suspect neoplasia in these globes.
PROCEDURES: The archives at the Comparative Ocular Pathology Laboratory of
Wisconsin (COPLOW) were searched to identify neoplasia-free feline globes
enucleated for suspected neoplasia. Clinical data were obtained from medical
records, veterinarian surveys, and COPLOW submission forms. All samples were
examined grossly and histologically. RESULTS: All eyes were free of neoplasia and
contained one or more iridociliary cysts. Nine of 14 globes were enucleated by or
based on the recommendation of a board-certified veterinary ophthalmologist. In
eight of 14 cases, the submitting clinician listed melanoma as the only suspected
diagnosis; in six of 14 cases, 'tumor' or 'mass' was listed. Clinical examination
revealed a darkly pigmented intraocular mass in 11 of 14 cases. The mass was
clinically perceived to be within the iris in seven of 14 cases. When examined
histologically, 11 of 14 eyes contained multiple cysts, 13 of 14 contained
multiloculated cysts, eight of 14 had a hyperplastic iris pigmented epithelium or
cysts with thick black walls, and five of 14 had cysts prolapsed into the
anterior chamber. CONCLUSIONS: Although most iridociliary cysts in cats are
easily diagnosed on clinical examination, a subset may be mistaken for neoplasia.
In cases of suspected iris melanoma, iridociliary cysts should be considered as a
differential diagnosis, especially if a mass appears to emanate from behind the
iris, dyscoria is present, or if similar changes are noted in the contralateral
eye.
PMID- 28685999
TI - Life prediction for a vacuum fluorescent display based on two improved models
using the three-parameter Weibull right approximation method.
AB - To obtain precise life information for vacuum fluorescent displays (VFDs),
luminance degradation data for VFDs were collected from a group of normal life
tests. Instead of exponential function, the three-parameter Weibull right
approximation method (TPWRAM) was applied to describe the luminance degradation
path of optoelectronic products, and two improved models were established. One of
these models calculated the average life by fitting average luminance degradation
data, and the other model obtained VFD life by combining the approximation method
with luminance degradation test data from each individual sample. The results
indicated that the test design under normal working stress was appropriate, and
the selection of censored test data was simple. The two models improved by TPWRAM
both revealed the luminance decaying law for VFD, and the pseudo failure time was
accurately extrapolated. It was further confirmed by comparing relative error
that using the second model gave a more accurate prediction of VFD life. The
improved models in this study can provide technical references for researchers
and manufacturers in aspects of life prediction methodology for its development.
PMID- 28686000
TI - Effect of near-infrared rays on female menstrual pain in Korea.
AB - Most Korean women who experience menstrual pain have reported taking pain
medicine and making use of complementary alternative therapies. However, because
some interventions may cause side effects, more effective pain-relieving measures
need to be identified. This study using a non-equivalent group design, evaluated
the effects of near-infrared rays on dysmenorrhea among Korean women. The
experimental group wore a near-infrared ray abdominal belt for the duration of
one menstrual cycle until the end of the menstrual period, while the control
group used hot packs. The level of menstrual pain, menstrual pain duration, and
pain medicine use were measured. The menstrual pain, average menstrual pain
duration, and use of analgesics were reduced in the near-infrared rays group. The
results of this study indicate that the near-infrared ray LED belt was effective
in reducing menstrual pain, menstrual pain duration compared to the use of
analgesics in Korean women with dysmenorrhea. Therefore, near-infrared rays may
be used to relieve menstrual pain and improve the quality of life of women with
dysmenorrhea in Korea.
PMID- 28686001
TI - Recreational sandboxes for children and dogs can be a source of epidemic
ribotypes of Clostridium difficile.
AB - Different studies have suggested that the sand of public playgrounds could have a
role in the transmission of infections, particularly in children. Furthermore,
free access of pets and other animals to the playgrounds might increase such a
risk. We studied the presence of Clostridium difficile in 20 pairs of sandboxes
for children and dogs located in different playgrounds within the Madrid region
(Spain). Clostridium difficile isolation was performed by enrichment and
selective culture procedures. The genetic (ribotype and amplified fragment length
polymorphism [AFLP]) diversity and antibiotic susceptibility of isolates was also
studied. Overall, 52.5% (21/40) of samples were positive for the presence of C.
difficile. Eight of the 20 available isolates belonged to the toxigenic ribotypes
014 (n = 5) and 106 (n = 2), both regarded as epidemic, and CD047 (n = 1). The
other 12 isolates were non-toxigenic, and belonged to ribotypes 009 (n = 5), 039
(n = 4), and 067, 151 and CD048 (one isolate each). Nevertheless, all isolates
(even those of a same ribotype) were classified into different AFLP genotypes
indicating non-relatedness. In conclusion, our results revealed the presence of
epidemic ribotypes of C. difficile in children's and dog's sandboxes located
nearby, which constitutes a major health risk.
PMID- 28686002
TI - Cerebrocortical activity during self-paced exercise in temperate, hot and hypoxic
conditions.
AB - AIM: Heat stress and hypoxia independently influence cerebrocortical activity and
impair prolonged exercise performance. This study examined the relationship
between electroencephalography (EEG) activity and self-paced exercise performance
in control (CON, 18 degrees C, 40% RH), hot (HOT, 35 degrees C, 60% RH) and
hypoxic (HYP, 18 degrees C, 40% RH FiO2 : 0.145) conditions. METHODS: Eleven
well-trained cyclists completed a 750 kJ cycling time trial in each condition on
separate days in a counterbalanced order. EEG activity was recorded with alpha-
and beta-activity evaluated in the frontal (F3 and F4) and central (C3 and C4)
areas. Standardized low-resolution brain electromagnetic tomography (sLORETA) was
also utilized to localize changes in cerebrocortical activity. RESULTS: Both
alpha- and beta-activity decreased in the frontal and central areas during
exercise in HOT relative to CON (P < 0.05). alpha-activity was also lower in HYP
compared with CON (P < 0.05), whereas beta-activity remained similar. beta
activity was higher in HYP than in HOT (P < 0.05). sLORETA revealed that alpha-
and beta-activity increased at the onset of exercise in the primary somatosensory
and motor cortices in CON and HYP, while only beta-activity increased in HOT. A
decrease in alpha- and beta-activity occurred thereafter in all conditions, with
alpha-activity being lower in the somatosensory and somatosensory association
cortices in HOT relative to CON. CONCLUSION: High-intensity prolonged self-paced
exercise induces cerebrocortical activity alterations in areas of the brain
associated with the ability to inhibit conflicting attentional processing under
hot and hypoxic conditions, along with the capacity to sustain mental readiness
and arousal under heat stress.
PMID- 28686003
TI - The Finnish national guideline for diagnosis, treatment and follow-up of patients
with wet age-related macular degeneration.
AB - Age-related macular degeneration (AMD) is the main cause of visual impairment in
developed countries. Several improvements in the visualization of posterior
segment of the eye together with the introduction of intravitreal anti-VEGF
treatment have revolutionized the prognosis of the wet form of AMD (wAMD).
Increasing incidence of wAMD together with the limited resources of society and
of the healthcare system poses challenges for the provision and development of
care. In context of these current aspects, we aimed to set evidence-based medical
guidelines for diagnosis, treatment and follow-up of patients with wAMD.
PMID- 28686004
TI - Bioglass(r) 45S5-based composites for bone tissue engineering and functional
applications.
AB - Bioglass(r) 45S5 (BG) has an outstanding ability to bond with bones and soft
tissues, but its application as a load-bearing scaffold material is restricted
due to its inherent brittleness. BG-based composites combine the amazing
biological and bioactive characteristics of BG with structural and functional
features of other materials. This article reviews the composites of Bioglass(r)
in combination with metals, ceramics and polymers for a wide range of potential
applications from bone scaffolds to nerve regeneration. Bioglass(r) also
possesses angiogenic and antibacterial properties in addition to its very high
bioactivity; hence, composite materials developed for these applications are also
discussed. BG-based composites with polymer matrices have been developed for a
wide variety of soft tissue engineering. This review focuses on the research that
suggests the suitability of BG-based composites as a scaffold material for hard
and soft tissues engineering. Composite production techniques have a direct
influence on the bioactivity and mechanical behavior of scaffolds. A detailed
discussion of the bioactivity, in vitro and in vivo biocompatibility and
biodegradation is presented as a function of materials and its processing
techniques. Finally, an outlook for future research is also proposed. (c) 2017
Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 3197-3223, 2017.
PMID- 28686005
TI - Vitamin D and osteoarthritis: disparity between observational studies and
clinical trials.
PMID- 28686007
TI - Imaging of primary liver tumors with positron-emission tomography.
AB - INTRODUCTION: The use of positron-emission tomography (PET) with
fluorodeoxyglucose (FDG), 11C-acetate and radio-labelled choline such as 11C
choline or 18F-fluorocholine in the diagnosis of hepatocellular carcinoma (HCC),
for risk stratification or therapy monitoring has emerged. This review aims to
summarize the published results dealing with this issue. EVIDENCE ACQUISITION:
PubMed database was searched until February 2017. Sensitivities, specificities,
progression-free survival (PFS), survival and hazard ratios (HR) are reported.
EVIDENCE SYNTHESIS: Seventy-one studies were included. Most studies are dealing
with the diagnostic value of FDG PET (N.=21), 11C-acetate PET (N.=11), and
choline PET (N.=8). The results indicate a homogenously higher sensitivity for
11C-acetate and choline PET as compared to FDG PET in the diagnosis of primary or
recurrent HCC. This is particularly true for well differentiated HCC, which tend
to have higher uptake of 11C-acetate and radio-labelled choline. Contrary, poorly
differentiated HCC are more often FDG-positive than well differentiated HCC.
Sixteen studies are evaluating the prognostic value of FDG PET for surgery or
liver transplantation. The studies found a significant worse prognosis in terms
of time to recurrence, PFS, and survival in FDG-positive HCC as compared to FDG
negative ones. Sixteen studies are reporting about the prognostic value of FDG
PET and one about 18F-fluoroethylcholine PET for palliative treatment. Most of
these studies indicate a significant shorter PFS and survival in FDG-positive HCC
for various treatments. CONCLUSIONS: Whereas FDG PET has only a limited role in
the diagnosis of HCC, it provides valuable prognostic information for liver
surgery, transplantation and palliative treatment. 11C-acetate and choline PET
have a higher sensitivity in the diagnosis of HCC.
PMID- 28686006
TI - Mindfulness-Based Stress Reduction in Women with Overweight or Obesity: A
Randomized Clinical Trial.
AB - OBJECTIVE: To evaluate the feasibility and cardiometabolic effects of mindfulness
based stress reduction (MBSR) in women with overweight or obesity. METHODS:
Eighty-six women with BMI >= 25 kg/m2 were randomized to 8 weeks of MBSR or
health education and followed for 16 weeks. The primary outcome was the Toronto
Mindfulness Scale. Secondary outcomes included the Perceived Stress Scale-10,
fasting glucose, and blood pressure. RESULTS: Compared to health education, the
MBSR group demonstrated significantly improved mindfulness at 8 weeks (mean
change from baseline, 4.5 vs. -1.0; P = 0.03) and significantly decreased
perceived stress at 16 weeks (-3.6 vs. -1.3, P = 0.01). In the MBSR group, there
were significant reductions in fasting glucose at 8 weeks (-8.9 mg/dL, P = 0.02)
and at 16 weeks (-9.3 mg/dL, P = 0.02) compared to baseline. Fasting glucose did
not significantly improve in the health education group. There were no
significant changes in blood pressure, weight, or insulin resistance in the MBSR
group. CONCLUSIONS: In women with overweight or obesity, MBSR significantly
reduces stress and may have beneficial effects on glucose. Future studies
demonstrating long-term cardiometabolic benefits of MBSR will be key for
establishing MBSR as an effective tool in the management of obesity.
PMID- 28686008
TI - Highly Efficient CO2 Electrolysis on Cathodes with Exsolved Alkaline Earth Oxide
Nanostructures.
AB - The solid oxide CO2 electrolyzer has the potential to provide storage solutions
for intermittent renewable energy sources as well as to reduce greenhouse gas
emissions. One of the key challenges remains the poor adsorption and activity
toward CO2 reduction on the electrolyzer cathode at typical operating conditions.
Here, we show a novel approach in tailoring a perovskite titanate (La,
Sr)TiO3+delta cathode surface, by the in situ growing of SrO nanoislands from the
host material through the control of perovskite nonstoichiometry. These
nanoislands provide very enhanced CO2 adsorption and activation, with stability
up to 800 degrees C, which is shown to be in an intermediate form between
carbonate ions and molecular CO2. The activation of adsorbed CO2 molecules
results from the interaction of exsolved SrO nanoislands and the defected
titanate surface as revealed by DFT calculations. These cathode surface
modifications result in an exceptionally high direct CO2 electrolysis performance
with current efficiencies near 100%.
PMID- 28686010
TI - Monoclinic ZIF-8 Nanosheet-Derived 2D Carbon Nanosheets as Sulfur Immobilizer for
High-Performance Lithium Sulfur Batteries.
AB - 2D hierarchically porous carbon (2D-HPC) nanosheets with unique advantages are
highly desired as host materials for lithium sulfur (Li-S) batteries and other
energy storage devices. Herein, we propose a self-template and organic solvent
free approach to synthesize nanosheets of monoclinic ZIF-8 at room temperature
from which 2D-HPC nanosheets (ZIF-8 nanosheets carbon denoted as ZIF-8-NS-C) are
derived to be an efficient sulfur immobilizer for Li-S batteries for the first
time. The anisotropic nanosheets are believed to relate to the symmetry of the
monoclinic structure. The 2D ZIF-8-NS-C nanosheets with embedded hierarchical
pores construct an effective conductive network through "plane-to-plane" modes to
endow superior electron transfer and fast electrochemical kinetics. Moreover, the
nitrogen-rich feature of ZIF-8-NS-C can increase the affinity/interaction of
carbon host with lithium polysulfides, favoring the cyclic performance. The
sulfur/ZIF-8-NS-C (S/ZIF-8-NS-C) cathode shows a superior rate capability with
high capacities of 1226 mA h g-1 at 0.2 C and 785 mA h g-1 at 2 C, and a
sustainable cycling stability with a capacity attenuation of 0.12% per cycle at
0.5 C for 300 cycles. The approach proposed here pioneers the controllable design
of MOF-based structures to inspire the exploration of more variable MOF-derived
porous materials for energy storage applications.
PMID- 28686009
TI - Ferrocenyl, Ruthenocenyl, and Benzyl Oxamniquine Derivatives with Cross-Species
Activity against Schistosoma mansoni and Schistosoma haematobium.
AB - Schistosomiasis is a parasitic disease that affects more than 250 million people
annually, mostly children in poor, tropical, rural areas. Only one treatment
(praziquantel) is available, putting control efforts at risk should resistance
occur. In pursuit of treatment alternatives, we derivatized an old
antischistosomal agent, oxamniquine (OXA). Four organometallic derivatives of OXA
were synthesized and tested against Schistosoma mansoni in vitro and in vivo. Of
these, a ferrocenyl derivative, 1, killed larval and adult worms 24 h
postexposure in vitro, in contrast to OXA, which lacks in vitro activity against
adult worms. A dose of 200 mg/kg of 1 completely eliminated the worm burden in
mice. Subsequently, a ruthenocenyl (5) and a benzyl derivative (6) of OXA were
synthesized to probe the importance of the ferrocenyl group in 1. Compounds 1, 5,
and 6 were lethal to both S. mansoni and S. haematobium adults in vitro. In vivo,
at 100 mg/kg, all three compounds revealed S. mansoni worm burden reductions of
76 to 93%, commensurate with OXA. Our findings present three compounds with
activity against S. mansoni in vitro, comparable activity in vivo, and high
activity against S. haematobium in vitro. These compounds may possess a different
binding mode or mode of action compared to OXA and present excellent starting
points for further SAR studies.
PMID- 28686011
TI - Glucosylceramide and Glucosylsphingosine Quantitation by Liquid Chromatography
Tandem Mass Spectrometry to Enable In Vivo Preclinical Studies of Neuronopathic
Gaucher Disease.
AB - Gaucher disease (GD) is caused by mutations in the GBA1 gene that encodes the
lysosomal enzyme acid beta-glucosidase (GCase). Reduced GCase activity primarily
leads to the accumulation of two substrates, glucosylceramide (GlcCer) and
glucosylsphingosine (GlcSph). Current treatment options have not been shown to
ameliorate the neurological pathology observed in the most severe forms of GD,
clearly representing an unmet medical need. To better understand the relationship
between GlcCer and GlcSph accumulation and ultimately their connection with the
progression of neurological pathology, we developed LC-MS/MS methods to quantify
GlcCer and GlcSph in mouse brain tissue. A significant challenge in developing
these methods was the chromatographic separation of GlcCer and GlcSph from the
far more abundant isobaric galactosyl epimers naturally occurring in white
matter. After validation of both methods, we evaluated the levels of both
substrates in five different GD mouse models, and found significant elevation of
brain GlcSph in all five, while GlcCer was elevated in only one of the five
models. In addition, we measured GlcCer and GlcSph levels in the brains of wild
type mice after administration of the GCase inhibitor conduritol beta-epoxide
(CBE), as well as the nonlysosomal beta-glucosidase (GBA2) inhibitor N
butyldeoxygalactonojirimycin (NB-DGJ). Inhibition of GCase by CBE resulted in
elevation of both sphingolipids; however, inhibition of GBA2 by NB-DGJ resulted
in elevation of GlcCer only. Taken together, these data support the idea that
GlcSph is a more selective and sensitive biomarker than GlcCer for neuronopathic
GD in preclinical models.
PMID- 28686012
TI - Efficient Encapsulation and Sustained Release of Basic Fibroblast Growth Factor
in Nanofilm: Extension of the Feeding Cycle of Human Induced Pluripotent Stem
Cell Culture.
AB - Basic fibroblast growth factor (bFGF) has an established pivotal function in
biomedical engineering, especially for the human pluripotent stem cells (iPSCs).
However, the limitation of bFGF is the ease of denaturation under normal
physiological conditions, inducing loss of its activity. In this study, we
designed multi-trilayered nanofilm composed of a repeating
polycation/polyanion/bFGF structure, which has high loading efficiency and short
buildup time. We also investigated that the loading and release of bFGF from the
nanofilm with two parameters (counter-polyanion and film architectures). Then, we
prepared the optimized nanofilm which maintains a sustained bFGF level in
physiological condition to apply the nanofilm to human iPSCs culture. The amount
of bFGF release from 12 trilayer nanofilm was 36.4 ng/cm2, and activity of bFGF
encapsulated into the nanofilm was maintained (60%) until 72 h during incubation
at 37 degrees C. As a result, the iPSCs grown in the presence of the nanofilm
with tridaily replacement of growth medium maintained undifferentiated morphology
and expression levels of pluripotency marker proteins.
PMID- 28686013
TI - Inline Shunt Flow Monitor for Hydrocephalus.
AB - In hydrocephalus, cerebrospinal fluid (CSF) builds up in the cranial cavity
causing swelling of the head and potentially brain damage. A shunt to drain the
fluid into a body cavity is now universally used, but failure is all too common.
Techniques for ascertaining shunt failure are time-consuming, expertise
dependent, and often inconclusive. We report here an inline system that reliably
and quantitatively measures the CSF flow rate. The system uses a single
thermistor to both heat the surrounding and to sense the temperature. In the
heating mode, the thermistor is subjected to a 5 s voltage pulse. In the sensing
mode, it is part of a Wheatstone's bridge, the output being proportional to
temperature. The signal, Vi - Vf, which is the net change DeltaV in the bridge
output immediately before and after the heat pulse, depends both on the flow rate
and the surrounding temperature. In vitro, a single equation, flow rate = 3.75 *
10-6 * DeltaV(-9.568+1.088 Vi) provided good prediction for the flow rate, with
6.3% RMS relative error. The sensor behavior is reported for flow rates between 0
52.5 mL/h at 32-39 degrees C, adequately covering the range of interest.
PMID- 28686014
TI - Efficient Dual siRNA and Drug Delivery Using Engineered Lipoproteoplexes.
AB - An engineered supercharged coiled-coil protein (CSP) and the cationic
transfection reagent Lipofectamine 2000 are combined to form a lipoproteoplex for
the purpose of dual delivery of siRNA and doxorubicin. CSP, bearing an external
positive charge and axial hydrophobic pore, demonstrates the ability to condense
siRNA and encapsulate the small-molecule chemotherapeutic, doxorubicin. The
lipoproteoplex demonstrates improved doxorubicin loading relative to
Lipofectamine 2000. Furthermore, it induces effective transfection of GAPDH (60%
knockdown) in MCF-7 breast cancer cells with efficiencies comparing favorably to
Lipofectamine 2000. When the lipoproteoplex is loaded with doxorubicin, the
improved doxorubicin loading (~40 MUg Dox/mg CSP) results in a substantial
decrease in MCF-7 cell viability.
PMID- 28686015
TI - Effective Removal of Selenite and Selenate Ions from Aqueous Solution by Barite.
AB - In the present study, we explore a new application of Barite (BaSO4) as a
sequestering phase for selenite (Se(IV)) and selenate (Se(VI)) ions from aqueous
solutions because of the low solubility and high stability of Barite with its
ability to selectively incorporate a large amount of various ions. The uptake of
Se(IV) and Se(VI) during coprecipitation with Barite was investigated through
batch experiments to understand the factors controlling effective removal of
Se(IV) and Se(VI) from polluted water to Barite. The factors include (i) chemical
affinity related to the degree of surface complexation between Barite surface and
Se(IV)/Se(VI) ion and (ii) structural similarity related to the structural
geometry of incorporated ions into the substituted site. The uptake of Se(IV) by
Barite is dependent on pH, coexistent calcium ion, and sulfate concentration in
the initial solution, possibly due to their effects on the chemical affinity and
structural similarity. On the other hand, the uptake of Se(VI) by Barite was
strongly dependent on sulfate concentration in the initial solution, which is
only related to the structural similarity. This study describes the mechanisms
for Se distribution between Barite and water, thereby providing a good estimate
of its ability to effectively remove Se(IV) and Se(VI) from aqueous solutions
under optimized experimental parameters examined here.
PMID- 28686016
TI - A Combination of Guanidyl and Phenyl Groups on a Dendrimer Enables Efficient
siRNA and DNA Delivery.
AB - Gene therapy has received considerable attention due to its great potential in
the treatment of various diseases; however, the design of efficient and
biocompatible carriers for the delivery of siRNA as well as DNA still remains a
major challenge. In this study, we developed an efficient carrier for gene
delivery by modification of a compound containing both guanidyl and phenyl groups
on the surface of a cationic dendrimer. The guanidyl group on the dendrimer
facilitates nucleic acid condensation via specific guanidinium-phosphate
interactions, whereas the phenyl group on the polymer is critical for efficient
endosomal escape. The combination of guanidyl and phenyl shows a synergistic
effect in facilitated endocytosis. The designed material is much more efficient
in siRNA and DNA delivery than control materials such as dendrimers engineered
with a guanidyl or phenyl group only, as well as intact dendrimers, and shows
comparable efficacy to commercial transfection reagent Lipofectamine 2000. In
addition, the material and its complex with nucleic acid show minimal toxicity on
the transfected cells. This study provides a new strategy to develop
multifunctional polymers for efficient siRNA and DNA delivery.
PMID- 28686017
TI - Analysis and Characterization of Polychlorinated Hydroxybornanes as Metabolites
of Toxaphene Using a Polar Bear Model.
AB - Abiotic and biotic transformation of toxaphene (camphechlor) results in the
selective enrichment of recalcitrant congeners while other, less persistent
compounds of technical toxaphene (CTTs) are degraded. Until now, there has been
little knowledge on oxidation transformation of toxaphene. For instance, the
existence of hydroxylated CTTs (OH-CTTs) in authentic environmental and food
samples has not been proven. For this reason, we synthesized a mixture consisting
of tetra- to heptachlorinated OH-CTTs and simplified it by countercurrent
chromatography (CCC). Thus, 227 OH-CTTs were detected in the CCC fractions (12
tetra-, 117 penta-, 81 hexa-, and 17 heptachlorinated OH-CTTs), which was >50%
more than detected before the fractionation. One CCC fraction consisting of only
18 OH-CTTs was used to develop a sample cleanup method which aimed to remove
CTTs, isobaric PCBs, and sample matrix. The final cleanup procedure consisted of
(i) gel permeation chromatography (GPC) and adsorption chromatography using (ii)
deactivated and (iii) activated silica gel. Hence, up to 320 and 4350 MUg/kg
lipid weight of octa- and nonachlorinated CTTs were detected in four liver
samples and adipose tissue of polar bears, respectively. Furthermore, the
presence of one hexachlorinated OH-CTT isomer could be verified in the samples,
which was about 1% of the octachlorinated CTTs determined in the liver samples.
PMID- 28686018
TI - Detection of G-Quadruplex Structures Formed by G-Rich Sequences from Rice Genome
and Transcriptome Using Combined Probes.
AB - Putative G-quadruplex (G4) forming sequences (PQS) are highly prevalent in the
genome and transcriptome of various organisms and are considered as potential
regulation elements in many biological processes by forming G4 structures. The
formation of G4 structures highly depends on the sequences and the environment.
In most cases, it is difficult to predict G4 formation by PQS, especially PQS
containing G2 tracts. Therefore, the experimental identification of G4 formation
is essential in the study of G4-related biological functions. Herein, we report a
rapid and simple method for the detection of G4 structures by using a pair of
complementary reporters, hemin and BMSP. This method was applied to detect G4
structures formed by PQS (DNA and RNA) searched in the genome and transcriptome
of Oryza sativa. Unlike most of the reported G4 probes that only recognize part
of G4 structures, the proposed method based on combined probes positively
responded to almost all G4 conformations, including parallel, antiparallel, and
mixed/hybrid G4, but did not respond to non-G4 sequences. This method shows
potential for high-throughput identification of G4 structures in genome and
transcriptome. Furthermore, BMSP was observed to drive some PQS to form more
stable G4 structures or induce the G4 formation of some PQS that cannot form G4
in normal physiological conditions, which may provide a powerful molecular tool
for gene regulation.
PMID- 28686019
TI - Palladium-Catalyzed Intermolecular Oxidative Cyclization of Allyltosylamides with
AcOH: Assembly of 3-Pyrrolin-2-ones.
AB - The first example of Pd-catalyzed oxidative cyclization of allyltosylamides with
acetic acid is reported. This transformation involved C-N/C-C bond formation and
provided 3-pyrrolin-2-ones in a one-pot manner with easy-operation, excellent
atom economy and good yields. Mechanistic studies indicate that the reaction
proceeds through intermolecular aminopalladation, migratory insertion,
reinsertion and beta-hydride elimination processes.
PMID- 28686021
TI - Effect of the Thermocouple on Measuring the Temperature Discontinuity at a Liquid
Vapor Interface.
AB - The coupled heat and mass transfer that occurs in evaporation is of interest in a
large number of fields such as evaporative cooling, distillation, drying,
coating, printing, crystallization, welding, atmospheric processes, and pool
fires. The temperature jump that occurs at an evaporating interface is of central
importance to understanding this complex process. Over the past three decades,
thermocouples have been widely used to measure the interfacial temperature jumps
at a liquid-vapor interface during evaporation. However, the reliability of these
measurements has not been investigated so far. In this study, a numerical
simulation of a thermocouple when it measures the interfacial temperatures at a
liquid-vapor interface is conducted to understand the possible effects of the
thermocouple on the measured temperature and features in the temperature profile.
The differential equations of heat transfer in the solid and fluids as well as
the momentum transfer in the fluids are coupled together and solved numerically
subject to appropriate boundary conditions between the solid and fluids. The
results of the numerical simulation showed that while thermocouples can measure
the interfacial temperatures in the liquid correctly, they fail to read the
actual interfacial temperatures in the vapor. As the results of our numerical
study suggest, the temperature jumps at a liquid-vapor interface measured
experimentally by using a thermocouple are larger than what really exists at the
interface. For a typical experimental study of evaporation of water at low
pressure, it was found that the temperature jumps measured by a thermocouple are
overestimated by almost 50%. However, the revised temperature jumps are still in
agreement with the statistical rate theory of interfacial transport. As well as
addressing the specific application of the liquid-vapor temperature jump, this
paper provides significant insight into the role that heat transfer plays in the
operation of thermocouples in general.
PMID- 28686020
TI - Evans Enolates: Structures and Mechanisms Underlying the Aldol Addition of
Oxazolidinone-Derived Boron Enolates.
AB - The soft enolization of an acylated oxazolidinone using di-n-butylboron triflate
(n-Bu2BOTf) and trialkylamines and subsequent aldol addition was probed
structurally and mechanistically using a combination of IR and NMR
spectroscopies. None of the species along the reaction coordinate show a penchant
for aggregating. Complexation of the acylated oxazolidinone by n-Bu2BOTf was too
rapid to monitor, as was the subsequent enolization with Et3N (triethylamine).
The preformed n-Bu2BOTf.Et3N complex, displaying muted Lewis acidity and
affiliated tractable rates, reveals a rate-limiting complexation via a transition
structure with a complicated counterion. n-Bu2BOTf.i-Bu3N bearing a hindered
amine shifts the rate-limiting step to proton transfer. Rate studies show that
the aldol addition with isobutyraldehyde occurs as proffered by others.
PMID- 28686022
TI - NHC-Cu(I)-Catalyzed Friedlander-Type Annulation of Fluorinated o-Aminophenones
with Alkynes on Water: Competitive Base-Catalyzed Dibenzo[b,f][1,5]diazocine
Formation.
AB - An efficient, easily scalable synthesis of 4-trifluoromethylquinolines and
naphthydrines (as well as their difluoro- and perfluoro-analogues) as a result of
tandem direct catalytic alkynylation/dehydrative condensation of o
aminofluoromethylketones (o-FMKs), for the first time catalyzed by NHC-copper(I)
complexes on water, is reported. A wide range of terminal alkynes is tolerated
under the reaction conditions, including beta-lactam-, steroid-, and sugar
derived ones, leading to desired quinolines and naphthydrines with good yields.
Further investigations proved that o-FMKs could be efficiently transformed into a
rare class of heterocyclic compounds-dibenzo[b,f][1,5]diazocines-by a base
catalyzed condensation, also on water. The developed method was applied for gram
scale synthesis of a fluorinated analogue of G protein-coupled receptor
antagonist (GPR91).
PMID- 28686024
TI - Pyridine-Spiropyran Derivative as a Persistent, Reversible Photoacid in Water.
AB - A highly versatile water-soluble pyridine-spiropyran photoswitch is reported
which functions as photoacid in a wide pH range. Under neutral conditions, the
open-ring merocyanine (MC-) exists to 48% and closes quantitatively by
irradiation with visible light, while the reverse reaction occurs rapidly in the
dark or by irradiation at 340 nm. The different pKa of the pyridine nitrogen in
the closed spiropyran (4.8) and open merocyanine form (6.8) leads to a reversible
proton release in a pH range of 3-7. Only negligible hydrolytic decomposition was
observed in the pH range from 1 to 12. The application of potentially harmful UV
light can be circumvented due to the fast thermal ring-opening except for pH
values below 3. Its photoacidic properties make this compound an effective pH
regulating photoswitch in water and enable controlled proton-transfer processes
for diverse applications. Additionally, all of the involved protonated states of
the compound exhibit discriminative fluorescence features within certain pH
ranges, which even expands its utility to a light-controllable, pH-sensitive
fluorophore.
PMID- 28686023
TI - PHOXI: A High Quantum Yield, Solvent-Sensitive Blue Fluorescent 5
Hydroxytryptophan Derivative Synthesized within Ten Minutes under Aqueous,
Ambient Conditions.
AB - Multiple tryptophan (Trp) proteins are not amenable to fluorescence study because
individual residue emission is not resolvable. Biosynthetic incorporation of an
indole analogue such as 5-hydroxyindole has not provided sufficient spectroscopic
resolution because of low quantum yield and small emission shift. Here, 5
hydroxyindole is used as the starting framework for building a blue emitting
fluorophore of high quantum yield, 2-phenyl-6H-oxazolo[4,5-e]indole (PHOXI). This
is a three reagent reaction completed in 10 min under ambient conditions in
borate buffer at pH 8. Reaction conditions have been optimized using 5
hydroxyindole. Derivatization is demonstrated on tryptophanyl 5-hydroxytryptophan
(5-HTP) and a stable beta-hairpin "zipper" peptide with four tryptophan residues,
TrpZip2, where Trp 4 has been replaced with 5-HTP, W4 -> 5-HTP. Reaction
optimization yields a PHOXI fluorophore that is essentially free of byproducts.
Reaction specificity is demonstrated by the lack of reaction with N-acetyl
cysteine and amyloid beta-40, a peptide containing all amino acids except
tryptophan, proline, and cysteine and lacking 5-HTP. Fluorescence study of PHOXI
derivatized 5-hydroxyindole in different solvents reveals the sensitivity of
PHOXI to solvent polarity with a remarkable 87 nm red-shift in water relative to
cyclohexane while maintaining high quantum yield. Thus, PHOXI joins the ranks of
solvatochromic fluorophores such as PRODAN. Surprisingly, DFT calculations reveal
coplanarity of the oxazolo/indole extended ring system and the phenyl substituent
for both the HOMO and LUMO orbitals. Despite the crowded environment of three
additional Trps in TrpZip2, CD spectroscopy shows that the TrpZip2 beta-hairpin
structure is partially retained upon PHOXI incorporation. In an environment of
smaller residues, PHOXI incorporation can be less disruptive of protein secondary
structure, especially at molecular interfaces and other environments where there
is typically less steric hindrance.
PMID- 28686025
TI - Laterally pi-Extended Dithia[6]helicenes with Heptagons: Saddle-Helix Hybrid
Molecules.
AB - A laterally pi-extended dithia[6]helicene 1, representing an interesting saddle
helix hybrid molecule containing an unusual heptagon, has been synthesized by
MoCl5-mediated oxidative stitching of tetrakis(thienylphenyl)naphthalene
precursor 2 involving reactive-site capping by chlorination and subsequent Pd
mediated dechlorination of tetrachlorinated intermediate 1-Cl4. Highly distorted,
wide helical structures of dithia[6]helicenes (1 and 1-Cl4) were clarified by
single-crystal X-ray diffraction analyses where heterochiral slipped pi-pi
stacking was displayed in a one-dimensional fashion. Notably, theoretical studies
on the thermodynamic behavior of 1 predicted an extraordinarily high
isomerization barrier of 49.7 kcal.mol-1, which enabled optical resolution and
chiroptical measurements. Electronic structures of these huge helicenes were also
examined by photophysical and electrochemical measurements.
PMID- 28686026
TI - Interactions of Phospholipid Vesicles with Cationic and Anionic Oligomeric
Surfactants.
AB - This work studied the interactions of 1,2-dioleoyl-sn-glycero-3-phosphocholine
(DOPC) with cationic ammonium surfactants and anionic sulfate or sulfonate
surfactants of different oligomeric degrees, including cationic monomeric DTAB,
dimeric C12C3C12Br2, and trimeric DDAD as well as anionic monomeric SDS, dimeric
C12C3C12(SO3)2, and trimeric TED-(C10SO3Na)3. The partition coefficient P of
these surfactants between the DOPC vesicles and water was determined with
isothermal titration microcalorimetry (ITC) by titrating concentrated DOPC
solution into the monomer solution of these surfactants. It was found that the P
value increases with the increase of the surfactant oligomeric degree. Moreover,
the enthalpy change and the Gibbs free energy for the transition of these
surfactants from water into the DOPC bilayer become more negative with increasing
the oligomeric degree. Meanwhile, the calcein release experiment proves that the
surfactant with a higher oligomeric degree shows stronger ability of changing the
permeability of the DOPC vesicles. Furthermore, the solubilization of the DOPC
vesicles by these oligomeric surfactants was studied by ITC, turbidity, and
dynamic light scattering, and thus the phase boundaries for the surfactant/lipid
mixtures have been determined. The critical surfactant to lipid ratios for the
onset and end of the solubilization for the DOPC vesicles derived from the phase
boundaries decrease remarkably with increasing the oligomeric degree. Overall,
the surfactant with a larger oligomerization degree shows stronger ability in
incorporating into the lipid bilayer, altering the membrane permeability and
solubilizing lipid vesicles, which provides comprehensive understanding about the
effects of structure and shape of oligomeric surfactant molecules on lipid
surfactant interactions.
PMID- 28686027
TI - Pendant-Type Helicene Oligomers with p-Phenylene Ethynylene Main Chains:
Synthesis, Reversible Formation of Ladderlike Bimolecular Aggregates, and Control
of Intramolecular and Intermolecular Aggregation.
AB - Pendant-type (P)-helicene oligomers with p-phenylene ethynylene main chains up to
a tetramer were synthesized by a building block method. The (P)-tetramer
reversibly formed a ladderlike bimolecular aggregate upon cooling and
disaggregated upon heating in (trifluoromethyl)benzene. Two bis(tetramer)s, in
which two (P)-tetramers were connected by hexadecamethylene linkers, were also
synthesized. The head-to-tail bis(tetramer) formed an intramolecular aggregate,
and the head-to-head bis(tetramer) formed an intermolecular aggregate in toluene.
The results suggest the antiparallel aggregation structure of the pendant-type
(P)-tetramers. The structure of the linker was proven to be effective in
controlling intramolecular and intermolecular aggregations.
PMID- 28686028
TI - Correction to "Determination of Cell Doubling Times from the Return-on-Investment
Time of Photosynthetic Vesicles Based on Atomic Detail Structural Models".
PMID- 28686029
TI - 8OCB and 8CB Liquid Crystals Confined in Nanoporous Alumina: Effect of
Confinement on the Structure and Dynamics.
AB - The effect of oxygen substitution is studied in two homologous compounds of n
cyanobiphenyls with n = 8 in the bulk and under confinement within self-ordered
nanoporous alumina (AAO). Oxygen substitution in 8OCB increases the dipole moment
and stabilizes the crystalline, smectic, and nematic phases to higher
temperatures relative to 8CB. Within their smectic- A (SmA) phase both 8CB and
8OCB behave as weak viscoelastic solids with low shear moduli reflecting the
underlying supramolecular defect structure. Dielectric spectroscopy assisted by
DFT calculations identified strong dipolar associations within the isotropic
phases characterized by a Kirkwood-Frohlich interaction parameter, g ~ 0.36.
Dielectric spectroscopy further identified a slow process (~ kHz) of low
dielectric strength. The proximity of this process to the rheology time scale
suggests as common origin a cooperative relaxation of the defect structure.
Confinement alters the phase diagram by stabilizing certain crystalline phases
and by reducing the N-I transition temperature in agreement with surface tension
effects. However, the N-I transition seems to retain its first order character.
Surface treatment with n-decyltrichlorosilane results in destabilization of the
SmA phase at the expense of the N phase. This is consistent with a picture of
surface anchored LC molecules at the pore walls that stabilize the nematic phase.
PMID- 28686030
TI - Gate-Defined One-Dimensional Channel and Broken Symmetry States in MoS2 van der
Waals Heterostructures.
AB - We have realized encapsulated trilayer MoS2 devices with gated graphene contacts.
In the bulk, we observe an electron mobility as high as 7000 cm2/(V s) at a
density of 3 * 1012 cm-2 at a temperature of 1.9 K. Shubnikov-de Haas
oscillations start at magnetic fields as low as 0.9 T. The observed 3-fold Landau
level degeneracy can be understood based on the valley Zeeman effect. Negatively
biased split gate electrodes allow us to form a channel that can be completely
pinched off for sufficiently large gate voltages. The measured conductance
displays plateau-like features.
PMID- 28686032
TI - Correction to Fast Magnetic Domain-Wall Motion in a Ring-Shaped Nanowire Driven
by a Voltage.
PMID- 28686031
TI - Intramolecular Chirality Transfer [2 + 2] Cycloadditions of Allenoates and
Alkenes.
AB - Intramolecular chirality transfer [2 + 2] cycloaddition of enantiomerically
enriched allenoates and alkenes is presented. The use of a chiral catalyst was
found to be critical to achieve high levels of diastereoselectivity compared to
use of an achiral catalyst. The method developed leads to highly substituted
cyclobutanes that would be difficult to prepare by alternative methods.
PMID- 28686033
TI - Redox-Neutral Access to Sultams from 2-Nitrochalcones and Sulfur with Complete
Atom Economy.
AB - A catalyst-free, redox-neutral, and completely atom-economical synthesis of
sultams by simply heating 2-nitrochalcones with elemental sulfur in 3-picoline or
N-methylmorpholine is described. The S-N, C-S, and S?O bonds of the sulfonamide
are efficiently formed between the nitrogen atom of the 2-nitro group and the
alpha-carbon of the chalcones and elemental sulfur with the migration of two
oxygen atoms from the 2-nitro group to the sulfur atom.
PMID- 28686034
TI - Revealing Surface Elemental Composition and Dynamic Processes Involved in Facet
Dependent Oxidation of Pt3Co Nanoparticles via in Situ Transmission Electron
Microscopy.
AB - Since catalytic performance of platinum-metal (Pt-M) nanoparticles is primarily
determined by the chemical and structural configurations of the outermost atomic
layers, detailed knowledge of the distribution of Pt and M surface atoms is
crucial for the design of Pt-M electrocatalysts with optimum activity. Further,
an understanding of how the surface composition and structure of electrocatalysts
may be controlled by external means is useful for their efficient production.
Here, we report our study of surface composition and the dynamics involved in
facet-dependent oxidation of equilibrium-shaped Pt3Co nanoparticles in an
initially disordered state via in situ transmission electron microscopy and
density functional calculations. In brief, using our advanced in situ gas cell
technique, evolution of the surface of the Pt3Co nanoparticles was monitored at
the atomic scale during their exposure to an oxygen atmosphere at elevated
temperature, and it was found that Co segregation and oxidation take place on
{111} surfaces but not on {100} surfaces.
PMID- 28686035
TI - Nanoscale Chemical Processes Affecting Storage Capacities and Seals during
Geologic CO2 Sequestration.
AB - Geologic CO2 sequestration (GCS) is a promising strategy to mitigate
anthropogenic CO2 emission to the atmosphere. Suitable geologic storage sites
should have a porous reservoir rock zone where injected CO2 can displace brine
and be stored in pores, and an impermeable zone on top of reservoir rocks to
hinder upward movement of buoyant CO2. The injection wells (steel casings encased
in concrete) pass through these geologic zones and lead CO2 to the desired zones.
In subsurface environments, CO2 is reactive as both a supercritical (sc) phase
and aqueous (aq) species. Its nanoscale chemical reactions with geomedia and
wellbores are closely related to the safety and efficiency of CO2 storage. For
example, the injection pressure is determined by the wettability and permeability
of geomedia, which can be sensitive to nanoscale mineral-fluid interactions; the
sealing safety of the injection sites is affected by the opening and closing of
fractures in caprocks and the alteration of wellbore integrity caused by
nanoscale chemical reactions; and the time scale for CO2 mineralization is also
largely dependent on the chemical reactivities of the reservoir rocks. Therefore,
nanoscale chemical processes can influence the hydrogeological and mechanical
properties of geomedia, such as their wettability, permeability, mechanical
strength, and fracturing. This Account reviews our group's work on nanoscale
chemical reactions and their qualitative impacts on seal integrity and storage
capacity at GCS sites from four points of view. First, studies on dissolution of
feldspar, an important reservoir rock constituent, and subsequent secondary
mineral precipitation are discussed, focusing on the effects of feldspar
crystallography, cations, and sulfate anions. Second, interfacial reactions
between caprock and brine are introduced using model clay minerals, with focuses
on the effects of water chemistries (salinity and organic ligands) and water
content on mineral dissolution and surface morphology changes. Third, the
hydrogeological responses (using wettability alteration as an example) of clay
minerals to chemical reactions are discussed, which connects the nanoscale
findings to the transport and capillary trapping of CO2 in the reservoirs.
Fourth, the interplay between chemical and mechanical alterations of geomedia,
using wellbore cement as a model geomedium, is examined, which provides helpful
insights into wellbore and caprock integrities and CO2 mineralization. Combining
these four aspects, our group has answered questions related to nanoscale
chemical reactions in subsurface GCS sites regarding the types of reactions and
the property alterations of reservoirs and caprocks. Ultimately, the findings can
shed light on the influences of nanoscale chemical reactions on storage
capacities and seals during geologic CO2 sequestration.
PMID- 28686036
TI - Synthesis of Thieno-Fused Five- and Six-Membered Nitrogen and Oxygen Heterocycles
via Intramolecular Heteroannulation of 4,5-Substituted 3-Amino or 3-Hydroxy 2
Functionalized Thiophenes.
AB - Diverse general high-yield routes for novel thieno-fused five- and six-membered
nitrogen and oxygen heterocycles such as thieno[3,2-b]pyrroles, thieno[3,2
b]furans, thieno[3,2-b]indoles, thieno[3,2-b]benzofurans, thieno[3,2-b]pyridine-5
ones, thieno[3,2-b]pyran-5-ones, thieno[3,2-b]isoquinolin-5-ones, thieno[3,2
b]chromen-5-ones, thieno[3,2-b]quinolin-9-ones, and thieno[3,2-b]chromen-9-ones
have been developed via in situ or stepwise intramolecular heteroannulation of
newly synthesized 4,5-substituted 3-amino- or 3-hydroxy 2-functionalized
thiophenes. These substituted 3-amino/hydroxythiophenes were readily obtained in
high yields from easily accessible precursors, in a sequential one-pot process,
by treatment of a range of (het)aryl/unsubstituted acetonitriles or acetates with
(het)aryl dithioesters in the presence of LDA, followed by in situ alkylation
intramolecular condensation of the resulting enethiolate salts with
functionalized activated methylene halides. The functionalized activated
methylene halides employed in these reactions for the synthesis of various thieno
fused heterocycles were cinnamyl bromide, 2-bromobenzyl chloride, bromocrotonate,
2-(bromomethyl)benzoate, and 2-chlorophenacyl bromide. A few of the 4,5
substituted 3-amino/hydroxy-2-stryrylthiophenes (or 2-acrylates) displayed strong
fluorescence, and their absorption/emission spectra have also been examined.
PMID- 28686037
TI - Hydrophobin coating prevents Staphylococcus epidermidis biofilm formation on
different surfaces.
AB - Staphylococcus epidermidis is a significant nosocomial pathogen in predisposed
hosts because of its capability of forming a biofilm on indwelling medical
devices. The initial stage of biofilm formation has a key role in S. epidermidis
abiotic surface colonization. Recently, many strategies have been developed to
create new anti-biofilm surfaces able to control bacterial adhesion mechanisms.
In this work, the self-assembled amphiphilic layers formed by two fungal
hydrophobins (Vmh2 and Pac3) have proven to be able to reduce the biofilm formed
by different strains of S. epidermidis on polystyrene surfaces. The reduction in
the biofilm thickness on the coated surfaces and the preservation of cell
vitality have been demonstrated through confocal laser scanning microscope
analysis. Moreover, the anti-biofilm efficiency of the self-assembled layers on
different medically relevant materials has also been demonstrated using a CDC
biofilm reactor.
PMID- 28686038
TI - Fate of Articles and Authors with Approved Plagiarism after a 10-Year Period:
Cases from International PubMed Indexed Journals in Thailand and Reflection on
Responsibility.
PMID- 28686039
TI - Change detection of meaningful objects in real-world scenes in adolescents with
and without autism spectrum disorder.
AB - Previous research suggested that adolescents with autism spectrum disorder are
better than typically developing children in detecting local, non-social details
within complex visual scenes. To better understand these differences, we used the
image database by Sareen et al., containing the size and on-screen location
information of all changes in the images, in a change blindness paradigm. In this
task, an original and a modified real-world scene, separated by a gray blank,
alternate repeatedly until observers detect the change. Our results indicated
that participants with and without autism spectrum disorder performed similarly
when scenes were presented upright, but that only the performance of the
typically developing adolescents became worse in the inverted scene condition. In
this condition, the correlation between performance and both image difficulty and
change predictability was significantly weaker in autism spectrum disorder than
in typically developing participants. We suggest that these findings result from
a more locally biased search strategy in people with autism spectrum disorder,
compared to typically developing participants, in tasks in which the rapid
processing of global information does not help to improve change detection
performance. Finally, although we found change location, change size, and age to
influence participant performance, none of these was directly linked to the
observed group-level differences.
PMID- 28686040
TI - Differentiation between Staphylococcus aureus and Staphylococcus epidermidis
strains using Raman spectroscopy.
AB - AIM: Raman spectroscopy is an analytical method with a broad range of
applications across multiple scientific fields. We report on a possibility to
differentiate between two important Gram-positive species commonly found in
clinical material - Staphylococcus aureus and Staphylococcus epidermidis - using
this rapid noninvasive technique. MATERIALS & METHODS: For this, we tested 87
strains, 41 of S. aureus and 46 of S. epidermidis, directly from colonies grown
on a Mueller-Hinton agar plate using Raman spectroscopy. DISCUSSION & CONCLUSION:
The method paves a way for separation of these two species even on high number of
samples and therefore, it can be potentially used in clinical diagnostics.
PMID- 28686041
TI - Relevance of Bolus Calculators in Current Hybrid Closed Loop Systems.
PMID- 28686043
TI - The role of nutrition in the pathophysiology and management of sickle cell
disease among children: A review of literature.
AB - Sickle cell disease (SCD) is one of the common inherited blood disorders in
humans and has been associated with decreased dietary intake which results in
poor nutritional status and impaired growth. Nutrition is one of the most
important but often forgotten aspect of care of patients with chronic disorders
and there have been emerging concern in literature on increased nutritional needs
of SCD patients. This paper sought to review the available literature on the
roles of individual nutrients in the pathophysiology and management of SCD among
children. Children with SCD have been shown to exhibit suboptimal status with
respect to both macronutrients and micronutrients. Thus, nutrition could play an
important role in the management of SCD. However, there is paucity of evidence
coming from trials with large sample sizes to support the suggestion that
supplementation with various nutrients that have been considered in this review
will be helpful.
PMID- 28686042
TI - The hepatitis E virus nonstructural polyprotein.
AB - Hepatitis E virus (HEV) is a globally important pathogen of acute and chronic
hepatitis in humans. The HEV ORF1 gene encodes a nonstructural polyprotein,
essential for RNA replication and virus infectivity. Expression and processing of
ORF1 polyprotein are shown in prokaryotic and eukaryotic systems, however, its
proteolysis into individual proteins is still debated. While molecular or
biochemical characterization of methyltransferase, protease, hypervariable
region, helicase and RNA polymerase domains in ORF1 has been achieved, the role
of the X and Y domains in the HEV life cycle has only been demonstrated very
recently. Clinically, detection of a number of ORF1 mutants in infected patients
is implicated in disease severity, mortality and drug nonresponse. Moreover,
several artificial lethal mutations in ORF1 offer a potential basis for
developing live-attenuated vaccines for HEV. This article intends to present the
molecular and clinical updates on the HEV ORF1 polyprotein.
PMID- 28686044
TI - Anti-biofilm properties of a mupirocin spray formulation against Escherichia coli
wound infections.
AB - Mupirocin ointment is a widely used topical drug for the treatment of bacterial
skin infections. However, ointments have some limitations which motivated the
development of a film forming spray of mupirocin. Mupirocin spray (2%) was
formulated with Eudragit E100 as a film forming agent and tested for its
antibacterial and anti-biofilm activities against Escherichia coli, a skin
pathogen causing wound and surgical site infections. Treatment with mupirocin
spray resulted in significant antibacterial and anti-biofilm activities
(inhibition and disruption) with single spray and sub-actual dose concentrations
at par with the commercial ointment concentration. The spray formulation was
found to be non-toxic to fibroblast cells and greatly resisted removal from the
site of application upon washing, in contrast to the ointment which was
significantly removed after a single wash. This is the first study to develop and
evaluate a spray formulation for mupirocin that forms a stable thin film for
sustained release of the drug.
PMID- 28686045
TI - Challenges of Diabetes Management in Toddlers.
AB - Toddlers with type 1 diabetes have distinctive combination of challenges to their
families and healthcare providers. A major factor is the difficulty in achieving
metabolic control without risking hypoglycemia. The rising incidence of type 1
diabetes in toddlers increases the magnitude of the problem and creates a greater
need for providing specialized service to cater for this age group's unique need.
Type 1 has a specific disease nature in younger children and its clinical
presentation mimics common childhood diseases. Symptoms and signs in the newly
presented toddler with diabetes might be unspecific causing diagnosis to be
missed or delayed. With the low cognitive ability and immature communication,
toddlers might not be able to express their ill-feeling resulting from
hypoglycemia or hyperglycemia. Hypoglycemia fear is common, which aggravates
stress and reduces adherence to strict metabolic control. Nocturnal hypoglycemia
is more common in toddlers and can be undiagnosed unless continuous glucose
monitoring is used. Insulin administration and adjustment can be challenging due
to pain, fear, refusal, and frequent intercurrent illness. Glucose monitoring is
crucial. However, it can be distressing to the child and difficult to adhere to
due to commitment or financial reasons. Insulin pump therapy is proven to be an
effective and a safe method of treatment for toddlers, but it requires intensive
training, resources, and long-term support. Provision of multidisciplinary team
with special expertise in managing toddlers with diabetes is essential. Providing
more physiological insulin regimes and customized technology is required to
improve treatment compliance and diabetes control.
PMID- 28686046
TI - The challenges of dysphagia in treating motor neurone disease.
AB - Motor neurone disease (MND) is a relatively rare degenerative disorder. Its
impacts are manifested in progressive loss of motor function and often
accompanied by wider non-motor changes. Swallowing and speech abilities are
frequently severely impaired. Effective management of dysphagia (swallowing
difficulty) symptoms and nutritional care requires a holistic multidisciplinary
approach. Care must be patient focused, facilitate patient decision making, and
support planning towards end of life care. This article discusses the challenges
of providing effective nutritional care to people living with motor neurone
disease who have dysphagia.
PMID- 28686047
TI - Home enteral feeding and its impact on quality of life.
PMID- 28686048
TI - Nutrition teams: what are they and why do we need them?
PMID- 28686049
TI - The British Journal of Nursing Nutrition Nurse of the Year 2017.
PMID- 28686050
TI - Parenteral nutrition: indications and safe management.
AB - The aim of this article is to provide an overview of what parenteral nutrition
(PN) is and when its use is required. It will describe the process of nutritional
assessment, and considerations when choosing venous access. The different
approaches to provision of PN solutions in hospital will be discussed. Catheter
related and metabolic complications can occur during delivery of PN; there will
be a discussion of the different types of complications and how these can be
avoided or minimised. Finally, the pivotal role of the nurse in the assessment
and ongoing care of patients who require PN will be highlighted, including skills
required to administer PN safely.
PMID- 28686051
TI - Can colour stimulate intake in older population groups?
PMID- 28686052
TI - Interview with Anne Holdoway.
PMID- 28686053
TI - The nursing crisis and its risk to essential care.
PMID- 28686054
TI - Finding the time: an audit of the acute ward mealtime processes.
AB - It has been found that many organisations still fail to meet the basic rights of
those in their care, in terms of access to food, drink and support when they need
it. In acknowledgment that food service in hospitals must be given a higher
priority, and be recognised as an integral part of the patient's treatment and
care, Irish hospitals must now have a system to evaluate the nutritional and
hydrational care for patients admitted to hospital. The purpose of this audit was
to examine the level of mealtime support available to patients during the main
mealtime service in our hospital. As the audit highlighted the need to alter ward
processes around the mealtime service, quality improvement initiatives were
introduced. These initiatives had a positive impact, enabling ward staff to
improve adequacy of mealtime support to patients, leading to better patient
quality care at this time.
PMID- 28686055
TI - A stakeholder-informed randomized, controlled comparative effectiveness study of
an order prescribing intervention to improve colony stimulating factor use for
cancer patients receiving myelosuppressive chemotherapy: the TrACER study.
AB - Colony stimulating factors (CSF) are widely prescribed to avoid febrile
neutropenia (FN) among cancer patients receiving chemotherapy, but studies show
their use is often not consistent with practice guidelines. In addition, there is
limited high quality evidence assessing benefits and harms of primary
prophylactic-CSF (PP-CSF) in the setting of chemotherapy that poses an
intermediate risk of FN. To address these issues, with funding from the Patient
Centered Outcomes Research Institute (PCORI) and the National Cancer Institute's
Community Oncology Research Program, SWOG is sponsoring a prospective, cluster
randomized controlled pragmatic trial of an automated order entry protocol for PP
CSF among patients with breast, lung and colorectal cancer receiving
myelosuppressive chemotherapy, with a nested randomized controlled trial of PP
CSF for patients receiving intermediate risk chemotherapy. Primary outcomes
include adherence to practice guidelines, overall rates of FN and rates of FN
among persons receiving intermediate risk chemotherapy. The study, the first
pragmatic trial in the National Cancer Institute's cancer cooperative clinical
trials network, will provide critical evidence to inform physician and patient
decision-making around PP-CSF use and practice policies regarding automated
orders in cancer components.
PMID- 28686057
TI - Patient-relevant outcomes associated with generic tamsulosin, levothyroxine and
amphetamine in the FDA Adverse Event Reporting System: a pilot study.
AB - AIM: Patient-reported outcomes associated with adverse events (AEs) reported with
generics have not been evaluated. To map AEs associated with generics to the NIH
Patient-reported Outcomes Measurement Information System. METHODS: We mapped 381
AEs from 148 case reports of generic tamsulosin, levothyroxine and
amphetamine/dextroamphetamine to the physical, mental and social domain of the
NIH Patient-Reported Outcomes Measurement Information System after reviewing 1237
case reports in the US FDA's Adverse Event Reporting System (FAERS; 2011-2013).
RESULTS: 75%, 76% and 71% reports were classified under the physical domain for
tamsulosin, levothyroxine and amphetamine/dextroamphetamine, while 9%, 9% and 18%
reports were classified under the mental domain, respectively. CONCLUSION: FAERS
reveals several domains of patient-relevant concerns associated with generic
drugs.
PMID- 28686056
TI - Proteomic profile of Mycobacterium tuberculosis after eupomatenoid-5 induction
reveals potential drug targets.
AB - AIM: We investigated a proteome profile, protein-protein interaction and
morphological changes of Mycobacterium tuberculosis after different times of
eupomatenoid-5 (EUP-5) induction to evaluate the cellular response to the drug
induced damages. METHODS: The bacillus was induced to sub-minimal inhibitory
concentration of EUP-5 at 12 h, 24 h and 48 h. The proteins were separated by 2D
gel electrophoresis, identified by LC/MS-MS. Scanning electron microscopy and
Search Tool for the Retrieval of Interacting Genes/Proteins analyses were
performed. RESULTS: EUP-5 impacts mainly in M. tuberculosis proteins of
intermediary metabolism and interactome suggests a multisite disturbance that
contributes to bacilli death. Scanning electron microscopy revealed the loss of
bacillary form. CONCLUSION: Some of the differentially expressed proteins have
the potential to be drug targets such as citrate synthase (Rv0896),
phosphoglycerate kinase (Rv1437), ketol-acid reductoisomerase (Rv3001c) and ATP
synthase alpha chain (Rv1308).
PMID- 28686058
TI - Genetic Associations and Interactions Between the NR3C1 (GR) and NR3C2 (MR) Genes
and Aggressive Behavior in a Central South Chinese Han Population.
AB - AIMS: The glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) play
important roles in the hypothalamic-pituitary-adrenal axis and stress regulation.
The current study aimed to address the genetic association and gene-gene
interactions between GR and MR gene polymorphisms and aggressive behavior.
METHODS: A haplotype-based, case-control study was designed to examine the
association between human MR and GR genes and aggressive behaviors, including
robbery and intentional interpersonal injury, in a central south Chinese Han
population. Eight well-studied polymorphisms of the MR gene (rs2070951, rs2871,
rs5522, and rs5525) and the GR gene (rs10482605, rs6190, rs1800445, and rs6196)
were genotyped using SNaPshot. RESULTS: The MR and GR gene polymorphisms were not
associated with aggressive behaviors, including in robbery and intentional
interpersonal injury subgroups (p > 0.05). The frequency of haplotype TAAT of GR
was significantly higher in the control group than that in the case group (p =
0.004, padj = 0.02). In addition, a two-way interaction between GR rs1800445 and
MR rs2070951 and aggressive behavior was also found (p = 0.01). CONCLUSIONS: The
haplotype TAAT of GR might be a protective factor against aggressive behavior,
while gene-gene interactions between GR rs1800445 and MR rs2070951 might be a
risk factor for aggressive behavior in the Central South Chinese Han population.
PMID- 28686059
TI - Household Diversion of Prescription Stimulants: Medication Misuse by Parents of
Children with Attention-Deficit/Hyperactivity Disorder.
AB - OBJECTIVES: The primary objective of this study is to investigate household
diversion of stimulant medication. Secondary objectives are to examine
clinical/demographic predictors of diversion, types of formulations diverted,
exposure to household diversion in the media, and storage of prescription
stimulants within households. METHODS: Questionnaires were completed by 180
parents of youth who were currently taking stimulant medication for treatment of
attention-deficit/hyperactivity disorder (ADHD). Parents were asked whether they
or another adult in the home had ever taken their child's stimulant medication or
given one child's stimulant medication to another child in the home.
Additionally, data regarding demographics, parental ADHD (diagnosed or
suspected), past suspicions of missing medication, and medication storage were
also collected. Responses were compared using Pearson's chi-squared test with
Yates' continuity correction. RESULTS: Sixteen percent of parents reported
diversion of stimulant medication to another household member, with the majority
admitting to taking the medication themselves. Another 13% had been tempted to
illicitly self-administer their child's medication. Parents with suspected or
diagnosed ADHD showed greater risk of self-administration or temptation to do so,
compared to parents without (33% vs. 17%, p = 0.01). The majority of parents
(71%) stored prescription stimulants "in plain sight," or "out of sight but
available to all." CONCLUSION: Although previous research has focused on peer
diversion among adolescents and young adults, clinicians must be vigilant for the
possibility of diversion by parents of children treated with stimulant
medication.
PMID- 28686060
TI - Show me the money! An analysis of underserved stakeholders' funding priorities in
Patient Centered Outcomes Research domains.
AB - AIM: Develop an accessible exercise to engage underserved populations about
research funding priorities; analyze the criteria they use to prioritize
research; contrast these criteria to those currently used by Patient Centered
Outcomes Research Institute (PCORI). MATERIALS & METHODS: Academic and community
partners collaborated to develop an Ipad exercise to facilitate group
deliberation about PCOR funding priorities. 16 groups (n = 183) of underserved
individuals in both urban and rural areas participated. Recordings were
qualitatively analyzed for prioritization criteria. RESULTS: Analysis yielded ten
codes, many of which were similar to PCORI criteria, but all of which challenged
or illuminated these criteria. CONCLUSION: Directly involving underserved
populations in determining funding criteria is both feasible and important, and
can better fulfill PCORI's goal of incorporating patient priorities.
PMID- 28686061
TI - LSD experiments by the United States Army.
AB - Extensive LSD testing was conducted by the US Army at Edgewood Arsenal and other
locations from 1955 to 1967. A number of different reports have been produced
describing the health effects of this testing, including the Veterans Health
Initiative Report in 2003. By and large, these reports gloss over and minimize
the short and long-term side effects and complications of this testing. However,
the reports themselves document frequent, severe complications of the LSD. These
side effects were regarded by the Army as having been directly caused by the LSD
exposure. In view of the current resurgence of interest in hallucinogens within
psychiatry, the sanitized version of the effects of LSD exposure on US soldiers
needs to be replaced with a more accurate account.
PMID- 28686062
TI - Psychometric properties and correlates of the PHQ-2 and PHQ-9 after traumatic
brain injury.
AB - PRIMARY OBJECTIVE: To determine the predictive accuracy of the Patient Health
Questionnaire (PHQ)-2 in predicting PHQ-9 findings and to examine demographic,
historical, and injury correlates of PHQ-9 ratings. RESEARCH DESIGN:
Retrospective analysis of data collected as part of routine clinical outpatient
care over a period of 30 months on 168 persons with mild to severe traumatic
brain injury, who were referred for neuropsychological evaluation within 1-12
months after injury. MAIN OUTCOMES AND RESULTS: PHQ-2 scores >=2 had a
sensitivity of 0.90 in predicting PHQ-9 scores >=10, and a sensitivity of 0.95 in
predicting endorsement of any passive or active suicidal thoughts on the PHQ-9.
Premorbid history of having experienced personal abuse was the strongest
predictor of post-injury PHQ-9 ratings. CONCLUSIONS: The PHQ-2 has adequate
sensitivity in predicting PHQ-9 findings and can be used as a screener in
clinical practice in persons with traumatic brain injury, as long as formal
psychometric assessment is supplemented with a comprehensive review of premorbid
history.
PMID- 28686063
TI - Accelerated cognitive aging following severe traumatic brain injury: A review.
AB - OBJECTIVE: The primary objective of this review was to examine relevant clinical
and experimental literatures for information on the long-term cognitive impact of
serious traumatic brain injury (TBI) with regard to the process of cognitive
aging. METHOD: Online journal databases were queried for studies pertaining to
cognitive aging in neurologically healthy populations, as well as the late
cognitive effects of serious TBI. Additional studies were identified through
searching bibliographies of related publications and using Google search engine.
RESULTS AND CONCLUSIONS: Problems of cognition exhibited by young adults after
TBI resemble many cognitive weaknesses of attention deficit and poor working
memory that are usually seen in an elderly population who have no neurological
history. The current state of the literature provides support for the argument
that TBI can result in diminished cognitive reserve which may accelerate the
normal process of cognitive decline, leading to premature aging, potentially
increasing the risk of dementia.
PMID- 28686064
TI - Awareness, treatment, control of hypertension, and associated factors: Results
from a Turkish national study.
AB - OBJECTIVE: Despite the fact that hypertension (HT) can be diagnosed and easily
treated, it is frequently not handled well throughout the world, and as a
developing country in Turkey. The objective of this study was to assess the
factors associated with the awareness, treatment, and control of HT in Turkey.
METHODS: Data came from Chronic Diseases and Risk Factors Survey, comprising a
nationally representative sample of 12,971 individuals, conducted by the Turkish
Ministry of Health in 2011. HT was defined as having systolic/diastolic blood
pressure (BP) at least 140/90 mmHg, usage of HT medicines, or having a previous
diagnosis. Awareness, treated, and controlled HT were determined by
questionnaires/BP measurements. Stepwise multiple logistic regression analysis
was used to estimate associated factors. RESULTS: The prevalence of HT was found
to be 24.8%. Awareness, treatment, and control rates were 65%, 59%, and 30%,
respectively. The risk factors for lack of awareness or treatment of HT were male
gender, young age, rural residency, lower education, being employed, sedentary
lifestyle, and less physical activity for women, unhealthy dietary habits for
men, and modifiable risk factors, including smoking and drinking for men.
Increasing age, low education for women, marital status subgroups within gender
(being single for men and being married for women), smoking and alcohol use for
men, and diseases such as diabetes and obesity were also correlated with poor
control of HT. CONCLUSION: This study recognized associated risk factors that may
guide policies and interventions to enhance awareness, treatment, and control of
HT in Turkey.
PMID- 28686065
TI - Behaviours of concern following moderate to severe traumatic brain injury in
individuals living in the community.
AB - PRIMARY OBJECTIVE: Behaviours of Concern (BoC) following traumatic brain injury
(TBI) have a significant negative impact on the daily functioning and quality of
life for the individual and their family. However, there has been limited
research examining the nature and severity of BoC beyond the acute recovery
period, including the perspective of the individual with TBI as well as close
others (COs). METHODS AND PROCEDURE: Eighty-nine individuals with predominantly
severe TBI, at a mean of 11.4 years' post-injury, were identified through a no
fault accident compensation system database. Structured interviews were completed
with 65 individuals with TBI, and 62 COs. Current BoC were documented using the
Overt Behaviour Scale (OBS). MAIN OUTCOMES AND RESULTS: 70.5% of participants
exhibited BoC on the OBS, with an average of 3 behaviours. Verbal aggression and
socially inappropriate behaviour were the most common BoC. Self-report of
behaviour change was endorsed by 81% of the sample. There was generally poor
concordance between the perspectives of the individual with the TBI and their CO.
CONCLUSION: Severe BoC, across multiple behaviour types, may be evident many
years following predominantly severe TBI. There is a need to provide long-term
behaviour support for these individuals.
PMID- 28686066
TI - Global Palliative Medicine.
PMID- 28686067
TI - Accents, Not Just Prosodic Boundaries, Influence Syntactic Attachment.
AB - Traditionally, pitch accents are understood to relate to the information
structure of a sentence and its discourse connections, while prosodic boundaries
indicate groupings of words and affect how constituents attach into a syntactic
structure. Here, we show that accents also affect syntactic attachment in
multiple different syntactic structures. Three auditory questionnaires on
ambiguous attachment sentences (such as Tom reported that Bill was bribed [last
May]) find that accenting the higher or lower verb ( reported or bribed)
increases the attachment of the final adverbial phrase as a modifier of the
accented verb. A fourth experiment shows that accents on verbs or object nouns
(in sentences like Jenny sketched a child [with crayons]) also increase the
attachment of the final prepositional phrase to the accented head (sketched with
crayons versus a child with crayons). Accent effects were small but consistent
across sentences with different levels of bias and did not depend on prosodic
boundaries. The results suggest that focused elements are important to the main
assertion of the sentence and therefore draw the attachment of upcoming material
(though the salience of attachment sites may also be important). The results also
demonstrate that both prosodic phrasing and pitch accents can affect basic
syntactic structure.
PMID- 28686069
TI - Heterocyclic thioglycosides in carbohydrate research: Synthesis of thiophene
thioglycosides.
AB - A novel synthesis of thiophene thioglycosides is carried out via a one-pot
reaction of sodium thiophenethiolates with alpha-halogeno sugars. The sodium
thiophenethiolate salts were prepared using sodium cyanoethylene thiolate salts.
The structures of the reaction products were established on the basis of their
elemental analysis and spectral data (IR, 1H NMR, MS, and 13C NMR).
PMID- 28686068
TI - Differential Associations Between Excess Body Weight and Psychiatric Disorders in
Men and Women.
AB - BACKGROUND: The current investigation is the first large-scale population-based
study from France that documents the association between excess body weight and
common psychiatric disorders, and examines the influence of gender on the
association between excess body weight and these disorders. A recent plan has
been implemented in France to treat the rising rate of those who are overweight
or obese, and we seek to demonstrate whether integrated treatment of excess
weight and psychiatric conditions appears as indicated. MATERIALS AND METHODS:
Data were drawn from a cross-sectional general population survey of 17,237
adults. Past-year psychiatric disorders were assessed using the Composite
International Diagnostic Interview-Short Form. Body mass index was used to
determine excess weight status. RESULTS: Overall, 3.7% of the sample were
underweight, 57% were normal weight, 28% were overweight (35% of men, 22% of
women), and 11% were obese (11% of men, 11% of women). Being overweight was more
common in men than women, although obesity did not differ by gender.
Sociodemographic variables significantly associated with weight status included,
age, marital status, education, employment status, income level, and population
density. Adjusting for these variables, being overweight was associated with
major depression and other disorders among women and inversely associated with
drug abuse and dependence among men. Obesity was associated with major
depression, panic disorder, agoraphobia, social phobia, specific phobia, and
obsessive-compulsive disorder among women. Only generalized anxiety was
associated with obesity among men. CONCLUSION: Past year, mental disorders were
more likely associated with being overweight or obese among women as compared
with men. The prevalence of these co-occurring psychiatric disorders in the
context of the rising rate of obesity in France indicates a clear need for
psychiatric assessment and treatment in caring for those with excess weight,
especially women. Preliminary reports suggest this need is unmet within the
otherwise progressive move in France to assist those struggling with excess
weight.
PMID- 28686070
TI - Effects of aging and rifampicin pretreatment on the pharmacokinetics of human
cytochrome P450 probes caffeine, warfarin, omeprazole, metoprolol and midazolam
in common marmosets genotyped for cytochrome P450 2C19.
AB - 1. The pharmacokinetics were investigated for human cytochrome P450 probes after
single intravenous and oral administrations of 0.20 and 1.0 mg/kg, respectively,
of caffeine, warfarin, omeprazole, metoprolol and midazolam to aged (10-14 years
old, n = 4) or rifampicin-treated/young (3 years old, n = 3) male common
marmosets all genotyped as heterozygous for a cytochrome P450 2C19 variant. 2.
Slopes of the plasma concentration-time curves after intravenous administration
of warfarin and midazolam were slightly, but significantly (two-way analysis of
variance), decreased in aged marmosets compared with young marmosets. The mean
hepatic clearances determined by in silico fitting for individual pharmacokinetic
models of warfarin and midazolam in the aged group were, respectively, 23% and
56% smaller than those for the young group. 3. Significantly enhanced plasma
clearances of caffeine, warfarin, omeprazole and midazolam were evident in young
marmosets pretreated with rifampicin (25 mg/kg daily for 4 days). Two- to three
fold increases in hepatic intrinsic clearance values were observed in the
individual pharmacokinetic models. 4. The in vivo dispositions of multiple
simultaneously administered drugs in old, young and P450-enzyme-induced marmosets
were elucidated. The results suggest that common marmosets could be experimental
models for aged, induced or polymorphic P450 enzymes in P450-dependent drug
metabolism studies.
PMID- 28686071
TI - Contralateral type of delayed endolymphatic hydrops may consist of two phenotypes
based on a magnetic resonance imaging preliminary study.
AB - OBJECTIVE: This study was performed to determine the volume distribution of EH in
contralateral DEH. PATIENTS AND METHODS: Five contralateral DEH patients (age
range = 21-77 years) and one ipsilateral DEH patient. Visualization of in vivo EH
using 3T magnetic resonance (MR) imaging was performed by intravenous
administration of gadolinium. The EH volume was determined quantitatively by
adding the area of EH in consecutive MR images. RESULTS: The total EH volume of
the patients with contralateral DEH varied from 24.2 to 56.6 MUL in the first ear
and 20.2 to 35.7 MUL in the contralateral ear. EH was dominantly developed in the
first ear for Patient no. 3 and 4, and not dominantly developed in the first ear
for Patient no. 1, 2, and 5. CONCLUSIONS: The volume distribution of
endolymphatic hydrops (EH) in contralateral delayed endolymphatic hydrops (DEH)
was classified into two phenotypes. This suggests that contralateral DEH may
consist of two etiologies.
PMID- 28686072
TI - Expression of masculine identity in individuals with a traumatic brain injury.
AB - PRIMARY OBJECTIVE: This research seeks to examine and describe how four males
with a traumatic brain injury (TBI) use language to negotiate their masculine
identities. RESEARCH DESIGN: Qualitative research methods were employed with a
'case study' design that allows for a detailed description of the cases, and the
interactions examined. METHODS AND PROCEDURES: The tools of inquiry applied
included a topic analysis, as well as linguistic analysis methods that
incorporated the theory of Systemic Functional Linguistics. Such tools were
employed in the analysis of 12, two-hour group treatment sessions in order to
describe how linguistic choices contributed to the construction of a masculine
identity in communicative interactions. MAIN OUTCOMES AND RESULTS: Although all
participants had significant difficulties with cognitive communication, they all
demonstrated an ability to use language to assert their masculine identities.
Results revealed that prominent topics used to assert masculinity included
confidence, women, risk-taking behaviour and interests and that expressions of
masculinity often occurred in giving information roles and involved appraisal and
modality. CONCLUSIONS: The results have implications for the development of
rehabilitation interventions for social communication that provide individuals
with TBI with the linguistic tools and communication opportunities necessary in
order to successfully express identity and reveal masculinity.
PMID- 28686073
TI - Effect of hypoxia on BOLD fMRI response and total cerebral blood flow in migraine
with aura patients.
AB - Experimentally induced hypoxia triggers migraine and aura attacks in patients
suffering from migraine with aura (MA). We investigated the blood oxygenation
level-dependent (BOLD) signal response to visual stimulation during hypoxia in MA
patients and healthy volunteers. In a randomized double-blind crossover study
design, 15 MA patients were allocated to 180 min of normobaric poikilocapnic
hypoxia (capillary oxygen saturation 70-75%) or sham (normoxia) on two separate
days and 14 healthy volunteers were exposed to hypoxia. The BOLD functional MRI
(fMRI) signal response to visual stimulation was measured in the visual cortex
ROIs V1-V5. Total cerebral blood flow (CBF) was calculated by measuring the blood
velocity in the internal carotid arteries and the basilar artery using phase
contrast mapping (PCM) MRI. Hypoxia induced a greater decrease in BOLD response
to visual stimulation in V1-V4 in MA patients compared to controls. There was no
group difference in hypoxia-induced total CBF increase. In conclusion, the study
demonstrated a greater hypoxia-induced decrease in BOLD response to visual
stimulation in MA patients. We suggest this may represent a hypoxia-induced
change in neuronal excitability or abnormal vascular response to visual
stimulation, which may explain the increased sensibility to hypoxia in these
patients leading to migraine attacks.
PMID- 28686074
TI - Simultaneous targeting of ATM and Mcl-1 increases cisplatin sensitivity of
cisplatin-resistant non-small cell lung cancer.
AB - Development of cisplatin-resistance is an obstacle in non-small cell lung cancer
(NSCLC) therapeutics. To investigate which molecules are associated with
cisplatin-resistance, we analyzed expression profiles of several DNA repair and
anti-apoptosis associated molecules in parental (A549P and H157P) and cisplatin
resistant (A549CisR and H157CisR) NSCLC cells. We detected constitutively
upregulated nuclear ATM and cytosolic Mcl-1 molcules in cisplatin-resistant cells
compared with parental cells. Increased levels of phosphorylated ATM (p-ATM) and
its downstream molecules, CHK2, p-CHK2, p-53, and p-p53 were also detected in
cisplatin-resistant cells, suggesting an activation of ATM signaling in these
cells. Upon inhibition of ATM and Mcl-1 expression/activity using specific
inhibitors of ATM and/or Mcl-1, we found significantly enhanced cisplatin
cytotoxicity and increased apoptosis of A549CisR cells after cisplatin treatment.
Several A549CisR-derived cell lines, including ATM knocked down (A549CisR-siATM),
Mcl-1 knocked down (A549CisR-shMcl1), ATM/Mcl-1 double knocked down (A549CisR
siATM/shMcl1) as well as scramble control (A549CisR-sc), were then developed.
Higher cisplatin-cytotoxicity and increased apoptosis were observed in A549CisR
siATM, A549CisR-shMcl1, and A549CisR-siATM/shMcl1 cells compared with A549CisR-sc
cells, and the most significant effect was shown in A549CisR-siATM/shMcl1 cells.
In in vivo mice studies using subcutaneous xenograft mouse models developed with
A549CisR-sc and A549CisR-siATM/shMcl1 cells, significant tumor regression in
A549CisR-siATM/shMcl1 cells-derived xenografts was observed after cisplatin
injection, but not in A549CisR-sc cells-derived xenografts. Finally, inhibitor
studies revealed activation of Erk signaling pathway was most important in
upregulation of ATM and Mcl-1 molcules in cisplatin-resistant cells. These
studies suggest that simultaneous blocking of ATM/Mcl-1 molcules or downstream
Erk signaling may recover the cisplatin-resistance of lung cancer.
PMID- 28686075
TI - Pharmacogenetics and the treatment of functional gastrointestinal disorders.
AB - The diagnosis and management of functional gastrointestinal disorders (FGIDs)
remain very challenging. In the era of precision medicine, it is important to
individualize the treatment of these conditions by providing targeted and
effective therapies while minimizing the risk of medication side effects. By
using genetic information that predicts and affects the responses to specific
medications, it is anticipated that the science of pharmacogenetics in FGIDs will
advance the practice of precision medicine. The pathophysiology of FGIDs is
complex, involving the interaction between predisposing genetic and environmental
factors. Studies have shown that genetic polymorphisms may contribute to the
variable responses to specific medications among individuals with FGIDs. Genetic
variations in the CYP450 system can affect the metabolism and, hence, the
pharmacokinetics of drugs used to treat FGIDs. Polymorphisms in the genes
controlling proteins that are involved in the direct action of medications
targeting the serotonergic, cannabinoid, adrenergic and bile acid pathways can
affect the pharmacologic effects of the medications. In this review, we summarize
the published literature on the pharmacogenetics of FGIDs and address the
potential clinical utility and future challenges in this field. Since it was the
dominant topic in the majority of the articles relevant to FGIDs, our review will
focus on irritable bowel syndrome.
PMID- 28686077
TI - Stressing the feedback: attention and cardiac vagal tone during a cognitive
stress task.
AB - OBJECTIVES: The present study examined relationships among gaze behaviour and
cardiac vagal tone using a novel stress-inducing task. METHODS: Participants' (N
= 40) eye movements and heart rate variability (HRV) were measured during an
unsolvable computer-based task randomly presenting feedback of "Right" and
"Wrong" answers distinctly onscreen after each trial. Subgroups were created on
the basis of more frequent eye movements to the right ("Correct"-Attenders; n =
23) or wrong ("Incorrect"-Attenders; n = 17) areas onscreen. RESULTS: Correct
Attenders maintained HRV from baseline to the stress task. In contrast, Incorrect
Attenders spent significantly more time viewing "Wrong" feedback, exhibited a
reduction in HRV during the stress condition (p < .01), and were more likely to
negatively self-evaluate performance. CONCLUSIONS: Results demonstrate that
pervasive attention to negative feedback ("Wrong") elicits perseverative stress
and negative self-evaluations among university students. This study highlights
the potential for studying attentional biases and emotional distress through
combined measures of gaze behaviour and cardiac vagal tone.
PMID- 28686078
TI - Effect of inhalation exposure to toluene on the activity of organic anion
transporting polypeptide (Oatp) using pravastatin as a probe drug in rats.
AB - 1. Toluene, used as a pure substance or in solvent mixtures, is the cause of
occupational exposures of large numbers of workers in the world. The organic
anion transporting polypeptides (OATP: human; Oatp: rodents) are drug carriers
which have been frequently associated to drug-drug interactions. The objective of
this study was to evaluate the influence of inhalation exposure to toluene in
Oatp in vivo activity using pravastatin as a probe drug in rats. 2. Male Wistar
rats ((n = 6 per sampling time) were exposed to 85 mg/m3 toluene by inhalation or
air in a nose only exposure system for 6 h/d, 5 d/week during 4 weeks, in order
to simulate the occupational exposure to toluene at level slightly above the
occupational exposure limit proposed by the American Conference of Governmental
Industrial Hygienists (ACGIH). After 4 weeks of exposure, animals received a
single dose of 20 mg/kg pravastatin orally. 3. Areas under concentration * time
curves extrapolated to infinite (AUC0-infinity) were calculated by Gauss Laguerre
quadrature. Non-exposed animals showed AUC0-infinity of 726.0 (261.8) ng h/mL for
pravastatin and rats exposed to toluene 85 mg/m3 showed AUC0-infinity of 681.8
(80.1) ng h/mL [data presented as mean (standard error of the mean)]. No
significant difference was observed in pravastatin kinetic disposition between
groups in terms of 95% confidence interval for the difference between means. 4.
Toluene exposure by inhalation did not change the in vivo activity of Oatp
evaluated by pravastatin kinetic disposition in rats.
PMID- 28686079
TI - Experimental Manipulation of Corticosterone Does Not Influence the Clearance Rate
of Plasma Testosterone in Birds.
AB - In vertebrates, exposure to acute stressors stimulates the secretion of adrenal
glucocorticoids such as corticosterone, and in some situations this hormone plays
an important role in orchestrating the trade-off that exists between reproduction
and self-maintenance. Stressful conditions often lead to a decrease in plasma
levels of sex steroids such as testosterone in males, and it has been
hypothesized that corticosterone contributes to this decrease. Generally
supporting this proposition, glucocorticoids can inhibit the reproductive axis
activity at multiple levels, including direct effects on testicular endocrine
function. Here we tested for the first time the additional hypothesis that stress
induced glucocorticoids are associated with an increased clearance rate of
circulating testosterone. To test this hypothesis, we performed two experiments
comparing changes in plasma testosterone as a function of time (6-60 min) after a
single injection of this hormone into captive male house finches (Haemorhous
mexicanus) that either were intact (controls) or were pharmacologically
adrenalectomized by administration of the glucocorticoid synthesis inhibitor
mitotane. Control finches rapidly elevated their plasma corticosterone in
response to handling, whereas mitotane treatment abolished this response by
approximately 95%. Contrary to our prediction, we found no clear evidence that
control birds eliminated exogenous testosterone from circulation at a different
rate than pharmacologically adrenalectomized finches. These findings do not
support the hypothesis that, during acute stress, elevated plasma glucocorticoids
stimulate the clearance rate of testosterone. The rapid inhibitory effect of
stress on plasma testosterone may rather result from direct actions of
glucocorticoids on the gonadal production of the androgen or involve a
glucocorticoid-independent mechanism.
PMID- 28686076
TI - Therapeutic implications of bioactive sphingolipids: A focus on colorectal
cancer.
AB - Therapy of colorectal cancer (CRC), especially a subset known as locally advanced
rectal cancer, is challenged by progression and recurrence. Sphingolipids, a
lipid subtype with vital roles in cellular function, play an important role in
CRC and impact on therapeutic outcomes. In this review we discuss how dietary
sphingolipids or the gut microbiome via alterations in sphingolipids influence
CRC carcinogenesis. In addition, we discuss the expression of sphingolipid
enzymes in the gastro-intestinal tract, their alterations in CRC, and the
implications for therapy responsiveness. Lastly, we highlight some novel
therapeutics that target sphingolipid signaling and have potential applications
in the treatment of CRC. Understanding how sphingolipid metabolism impacts cell
death susceptibility and drug resistance will be critical toward improving
therapeutic outcomes.
PMID- 28686081
TI - Letter to the editor concerning the article "Bar velocities capable of optimising
the muscle power in strength-power exercises" by Loturco, Pereira, Abad, Tabares,
Moraes, Kobal, Kitamura & Nakamura (2017).
AB - Loturco and co-workers (2017) recently published data in the Journal of Sports
Sciences to present the optimum loading magnitudes regarding the maximization of
the "mean propulsive power" of the leg and arm muscles. Among the most important
findings were that (1) the recorded power in the squat and squat jump exercises
was markedly low, (2) the optimum external load that maximized the power in the
same exercises was close to 100% of body weight, while (3) the ballistic bench
press throw revealed smaller power than the regular bench press typically
performed with relatively low level of muscle activation towards the end of the
propulsive lifting phase. The findings are either counter-intuitive, or
contradict the literature findings, or both, and we believe that they originate
from apparent methodological flaws. The first one is neglecting the force acting
against the body segments moved together with the external load that is
particularly high in squat exercises. The second one is an erroneous calculation
of the propulsive phase that included a part of the bar's flight time. Both of
these methodological flaws are frequent in the literature and could be associated
with the improper use and calculation of variables when utilizing linear position
transducers.
PMID- 28686080
TI - Influence of common and rare genetic variation on warfarin dose among African
Americans and European-Americans using the exome array.
AB - AIM: We conducted a genome-wide association study using the Illumina Exome Array
to identify coding SNPs that may explain additional warfarin dose variability.
PATIENTS & METHODS: Analysis was performed after adjustment for clinical
variables and genetic factors known to influence warfarin dose among 1680
warfarin users (838 European-Americans and 842 African-Americans). Replication
was performed in an independent sample. RESULTS: We confirmed the influence of
known genetic variants on warfarin dose variability. Our study is the first to
show the association between rs12772169 and warfarin dose in African-Americans.
In addition, genes COX15 and FGF5 showed significant association in European
Americans. CONCLUSION: We identified some novel genes/SNPs that underpin warfarin
dose response. Further replication is needed to confirm our findings.
PMID- 28686082
TI - Providing Dementia Consultations to Veterans Using Clinical Video Telehealth:
Results from a Clinical Demonstration Project.
AB - PURPOSE: Veterans with dementia and their caregivers in remote areas may not have
access to specialists to provide diagnosis, treatment, and education. The purpose
of this clinical demonstration project was to examine the feasibility,
acceptability, and impact of a video consultations clinic for veterans with
dementia or memory complaints and their caregivers. METHODS: The dementia
clinical video telehealth (CVT) consultation clinic was established to identify,
diagnose, and treat dementia in veterans at sites distant from the main medical
center. A geriatrician at the main facility provided video consultation to
patients and caregivers at seven satellite facilities. Diagnoses made and
services provided were recorded after the initial consultation. Patient and
caregiver satisfaction with the CVT clinic were assessed. FINDINGS: Ninety-four
patients were evaluated in the CVT dementia clinic (average age = 74.7; average
Mini-Mental State Exam = 24.4). Forty patients had a prior dementia diagnosis, 15
received a new dementia diagnosis, and 20 a new mild cognitive impairment
diagnosis. Of the remaining patients evaluated for memory complaints, seven were
found to have depression, three had hearing loss, and three had traumatic brain
injury. After CVT consultation, common referrals included social work (n = 43),
neuropsychology (n = 36), and brain imaging (n = 26). Patients and caregivers
expressed high satisfaction with the video consultation and 90% of caregivers
indicated they would rather use CVT than travel to see the specialist in person.
CONCLUSIONS: Video consultation was well accepted by both dementia patients and
caregivers. CVT may facilitate timely diagnosis and management and provide
support for rural dementia patients and caregivers.
PMID- 28686083
TI - Ischemic preconditioning enhances critical power during a 3 minute all-out
cycling test.
AB - This study tested the hypothesis that ischemic preconditioning (IPC) would
increase critical power (CP) during a 3 minute all-out cycling test. Twelve males
completed two 3 minute all-out cycling tests, in a crossover design, separated by
7 days. These tests were preceded by IPC (4 x 5 minute intervals at 220 mmHg
bilateral leg occlusion) or SHAM treatment (4 x 5 minute intervals at 20 mmHg
bilateral leg occlusion). CP was calculated as the mean power output during the
final 30 s of the 3 minute test with W' taken as the total work done above CP.
Muscle oxygenation was measured throughout the exercise period. There was a 15.3
+/- 0.3% decrease in muscle oxygenation (TSI; [Tissue saturation index]) during
the IPC stimulus, relative to SHAM. CP was significantly increased (241 +/- 65 W
vs. 234 +/- 67 W), whereas W' (18.4 +/- 3.8 vs 17.9 +/- 3.7 kJ) and total work
done (TWD) were not different (61.1 +/- 12.7 vs 60.8 +/- 12.7 kJ), between the
IPC and SHAM trials. IPC enhanced CP during a 3 minute all-out cycling test
without impacting W' or TWD. The improved CP after IPC might contribute towards
the effect of IPC on endurance performance.
PMID- 28686084
TI - Why and When do Patients Use e-Consultation Services? The Trust and Resource
Supplementary Perspectives.
AB - INTRODUCTION: e-Consultation provides a new way to deliver healthcare services
online. With the help of e-Consultation services, patients can gain access to
nationwide medical expertise that otherwise would not be available to them. As an
online delivery approach, e-Consultation also provides a choice for patients to
receive medical advice from online doctors immediately, no matter how far away
from the hospital they may be or how late in the day it is. However, the adoption
and usage of e-Consultation is still far from satisfactory. Therefore,
understanding why and when patients use e-Consultation services are important
research questions. MATERIALS AND METHODS: Considering that the choice of a
healthcare provider is a serious decision, this research uses the trust
perspective to explain the e-Consultation service adoption phenomenon.
Specifically, trust is conceptualized as a second-order construct consisting of
two dimensions: competence and integrity. In addition, e-Consultation is viewed
as a supplementary resource to traditional off-line consultation services, and
disease type as a contextual factor is hypothesized to focus the context where e
Consultation services are more suitable. A scenario-based survey was conducted to
test the proposed research model. We obtained a total of 190 valid
questionnaires. RESULTS: Our results indicated that trust (p < 0.01) had a
positive effect on the intention to use an e-Consultation service. Meanwhile, our
results also indicated that the higher the disease is in rarity (p < 0.05),
severity (p < 0.01), or urgency (p < 0.05), the lesser the positive effect of
trust is on the intention to use an e-Consultation service. CONCLUSIONS: Trust is
the major driving force of an e-Consultation service adoption. When the disease
is high in rarity, severity, or urgency, an off-line healthcare provider is less
capable of providing meaningful, qualified, and immediate service. Therefore,
there is a decreased positive effect of trust on the intention to use an e
Consultation service for those diseases.
PMID- 28686085
TI - Conceptualizing minimalist footwear: an objective definition.
AB - Running has been plagued with an alarmingly high incidence of injury, which has
resulted in the exploration of interventions aimed at reducing the risk of
running-related injury. One such intervention is the introduction of footwear
that mimics barefoot running. These have been termed minimalist shoes. Minimalist
footwear aims to reduce the risk of injury by promoting adaptations in running
biomechanics that have been linked to a reduction in both impact and joint
forces. However, some studies have found that minimalist footwear may be
beneficial to the runner as they promote favourable biomechanical adaptations,
whilst other studies have found the opposite to be true. Reasons for these
conflicting results could be attributed to the lack of a definition for
minimalist footwear. The aim of this review article is to provide a structural
definition for minimalist footwear based on studies that have examined the
influence of footwear on biomechanical variables during running. Based on current
literature, we define minimalist footwear as a shoe with a highly flexible sole
and upper that weighs 200g or less, has a heel stack height of 20mm or less and a
heel-toe differential of 7mm or less.
PMID- 28686087
TI - Differences in Fusarium Species in brown midrib Sorghum and in Air Populations in
Production Fields.
AB - Several Fusarium spp. cause sorghum (Sorghum bicolor) grain mold, resulting in
deterioration and mycotoxin production in the field and during storage. Fungal
isolates from the air (2005 to 2006) and from leaves and grain from wild-type and
brown midrib (bmr)-6 and bmr12 plants (2002 to 2003) were collected from two
locations. Compared with the wild type, bmr plants have reduced lignin content,
altered cell wall composition, and different levels of phenolic intermediates.
Multilocus maximum-likelihood analysis identified two Fusarium thapsinum
operational taxonomic units (OTU). One was identified at greater frequency in
grain and leaves of bmr and wild-type plants but was infrequently detected in
air. Nine F. graminearum OTU were identified: one was detected at low levels in
grain and leaves while the rest were only detected in air. Wright's F statistic
(FST) indicated that Fusarium air populations differentiated between locations
during crop anthesis but did not differ during vegetative growth, grain
development, and maturity. FST also indicated that Fusarium populations from wild
type grain were differentiated from those in bmr6 or bmr12 grain at one location
but, at the second location, populations from wild-type and bmr6 grain were more
similar. Thus, impairing monolignol biosynthesis substantially effected Fusarium
populations but environment had a strong influence.
PMID- 28686086
TI - A Risk Assessment Model for Bacterial Leaf Spot of Pepper (Capsicum annuum),
Caused by Xanthomonas euvesicatoria, Based on Concentrations of Macronutrients,
Micronutrients, and Micronutrient Ratios.
AB - The phytopathogenic bacterium Xanthomonas euvesicatoria causes bacterial leaf
spot (BLS) of pepper and has a worldwide distribution. BLS is difficult to
control and an integrated management strategy that incorporates crop rotation,
use of clean seed and clean plants, weed control, resistant varieties,
applications of bactericides, biocontrol agents, and systemic acquired resistance
(SAR) inducers is generally recommended. However, even with that arsenal of
weapons, BLS can still be responsible for severe losses under favorable
environmental conditions. Thus, additional tools need to be added to an overall
integrated management strategy to combat BLS. In this article, we developed
several models from 2012 to 2014 that were based on how macronutrients,
micronutrients, and micronutrient ratios affect BLS severity. Factors used to
select a model for validation included highly significant P values, high adjusted
R2 values, low variance inflation factor values (<5), root mean square error,
Mallow's Cp, and high Akaike's information criterion correction values. In
addition, salicylic acid (SA) concentrations and relative expression of
nonexpresser pathogenesis-related gene1 (NPR1) and pathogenesis-related protein 1
(PR1) in pepper tissues were also considered in model selection. A model (ECGA1)
consisting of concentrations of copper, manganese, potassium, and the iron/zinc
ratio as independent variables was used for validation in three different
commercial pepper fields in Georgia: Colquitt County and Worth County in 2015 and
Tift County in 2016. When area under the disease progress curve (AUDPC) values
for two field sites (Colquitt and Worth Counties) in 2015 were pulled together
and plotted against ECGA1-predicted values for both sites, the resulting
relationship was highly significant (P = 0.0001) with an R2 value of 0.92. A
significant relationship between observed AUDPC versus predicted values was also
observed in Tift County in 2016 (P < 0.001; adjusted R2 = 0.98). Relative gene
expression of both NPR1 and PR1 genes was significantly (P < 0.01) higher in
pepper grown in predicted low-risk sites compared with pepper from high-risk
sites in Colquitt, Worth, and Tift Counties. Although BLS severity will fluctuate
depending on environmental conditions, the data indicate that the level of risk
at a particular location may be influenced by how macronutrient and micronutrient
concentrations affect plant disease resistance genes in the SAR pathway.
PMID- 28686088
TI - Changing epidemiology of AA amyloidosis: clinical observations over 25 years at a
single national referral centre.
AB - OBJECTIVE: Systemic AA amyloidosis is a serious complication of chronic
inflammation; however, there are relatively few published data on its incidence.
We investigated the changing epidemiology of AA amyloidosis over a 25-year period
at a single national referral centre. METHODS: We conducted a retrospective study
of all patients diagnosed with AA amyloidosis who had attended the centre between
1990 and 2014 inclusive. Six hundred and twenty-five patients were studied in
three cohorts: C1: 1990-1997; C2: 1998-2006; C3: 2007-2014. RESULTS: Mean age at
presentation increased from 46 in C1 to 56 in C3 (p < .0001). The proportion of
South Asian patients increased from 4% in C1 to 17% in C3 (p = .0006). Comparison
of underlying diseases between C1 and C3 revealed a reduction in patients with
juvenile idiopathic arthritis from 25% to 2% (p < .0001), but an increase in
patients with chronic infection due to intravenous recreational drug use from 1%
to 13% (p < .0001), and uncharacterized inflammatory disorders from 10% to 27% (p
<.0001). More patients were in end-stage renal failure at presentation in C3
(29%) than C1 (15%) (p = .0028). Median age at death was later in C3 (62 years)
than C1 (54 years) (p = .0012). CONCLUSION: These data suggest both falling
incidence and better outcome in AA amyloidosis over a quarter of a century,
reflecting advances in therapeutics and overall management of complex chronic
disease in an ageing population. AA amyloidosis of uncertain aetiology presents
an emerging major problem. Newer techniques such as next-generation sequencing
may aid diagnosis and effective treatment, thereby improving overall survival.
PMID- 28686089
TI - Long-term influence of fixed lingual retainers on the development of gingival
recession: A retrospective, longitudinal cohort study.
AB - OBJECTIVE: To investigate the long-term influence of fixed lingual retainers on
the development of mandibular gingival recession and to compare the prevalence
with untreated individuals. MATERIALS AND METHODS: The material consisted of 144
subjects: 96 orthodontically treated patients followed for 5 years after therapy
and 48 untreated age-matched subjects. The treated patients were divided in two
groups: one receiving a fixed mandibular retainer (n = 48) and one receiving no
form of retention in the mandible (n = 48). The presence or absence of gingival
recession and calculus accumulation were scored before treatment (T0), after
debonding (T1), and 5 years after debonding (T5) for each tooth in the mandibular
intercanine region using plaster models and intraoral photographs. The chi-square
test, one-way ANOVA, and Cochran's Q test were used to evaluate inter- and
intragroup differences. RESULTS: The prevalence of patients with recession
increased gradually and significantly throughout the observation periods in all
groups, but the intergroup differences at T5 were not significant. Significantly
more calculus accumulation was observed at T5 in the retainer group compared with
the group without retainers. CONCLUSIONS: Long-term presence of fixed lingual
retainers does not seem to increase the development of mandibular gingival
recession, but does increase calculus accumulation.
PMID- 28686090
TI - How accurate is Invisalign in nonextraction cases? Are predicted tooth positions
achieved?
AB - OBJECTIVE: To evaluate the accuracy of Invisalign technology in achieving
predicted tooth positions with respect to tooth type and direction of tooth
movement. MATERIALS AND METHODS: The posttreatment models of 30 patients who had
nonextraction Invisalign treatment were digitally superimposed on their
corresponding virtual treatment plan models using best-fit surface-based
registration. The differences between actual treatment outcome and predicted
outcome were computed and tested for statistical significance for each tooth type
in mesial-distal, facial-lingual, and occlusal-gingival directions, as well as
for tip, torque, and rotation. Differences larger than 0.5 mm for linear
measurements and 2 degrees for angular measurements were considered clinically
relevant. RESULTS: Statistically significant differences (P < .05) between
predicted and achieved tooth positions were found for all teeth except maxillary
lateral incisors, canines, and first premolars. In general, anterior teeth were
positioned more occlusally than predicted, rotation of rounded teeth was
incomplete, and movement of posterior teeth in all dimensions was not fully
achieved. However, except for excess posttreatment facial crown torque of
maxillary second molars, these differences were not large enough to be clinically
relevant. CONCLUSIONS: Although Invisalign is generally able to achieve predicted
tooth positions with high accuracy in nonextraction cases, some of the actual
outcomes may differ from the predicted outcomes. Knowledge of dimensions in which
the final tooth position is less consistent with the predicted position enables
clinicians to build necessary compensations into the virtual treatment plan.
PMID- 28686091
TI - Correlation between the position of hyoid bone and subregions of the pharyngeal
airway space in lateral cephalometry and cone beam computed tomography.
AB - OBJECTIVE: To correlate the pharyngeal airway subregions with the positioning of
the hyoid bone. MATERIAL AND METHODS: The study examined 107 lateral
cephalometric (LC) and cone beam computed tomography (CBCT) images. Linear and
volumetric measurements of the pharyngeal subregions were made and correlated to
linear measurements using hyoid triangle analysis on images of LC and multiplanar
(MPR) and three-dimensional (3D) reconstructions of CBCT. RESULTS: There was
significant correlation between linear measurements of the pharyngeal subregions
and hyoid bone position in LC images and in MPR and 3D reconstructions of the
CBCT. Correlations were more frequent in the oropharynx and hypopharynx,
especially for LC images. No correlations were observed between LC images or CBCT
reconstructions and the volumetric measurements of the pharyngeal subregions and
the position of the hyoid bone. CONCLUSION: The hyoid bone position showed more
correlations with oropharynx and hypopharynx airway measurements. The hyoid
triangle method was not applicable to 3D images, since it showed a smaller number
of measures correlated to the hyoid bone position.
PMID- 28686092
TI - Association between orthodontic treatment and periodontal diseases: Results from
a national survey.
AB - OBJECTIVE: To investigate the association between orthodontic treatment and
periodontitis in a nationally representative sample of South Korea. MATERIALS AND
METHODS: Data from the Fifth and Sixth Korean National Health and Nutrition
Examination Survey (KNHANES V, VI-1, and VI-2), conducted from 2012 to 2014, were
used in this study. The final sample size consisted of 14,693 adults aged >=19
years. Logistic regression analysis was performed to assess the association
between orthodontic treatment and periodontitis. RESULTS: The orthodontic
treatment group exhibited a lower prevalence of periodontitis compared with the
nonorthodontic treatment group. The adjusted odds ratios for periodontitis in
subjects with a history of orthodontic treatment compared with those with no
history of orthodontic treatment were 0.553, 0.614, and 0.624, when adjusted for
various confounding variables (P < .0001). The subjects with periodontitis were
of higher age, body mass index, waist circumference, and white blood cell counts
compared with the subjects without periodontitis regardless of history of
orthodontic treatment. CONCLUSIONS: History of orthodontic treatment was
associated with a decreased rate of periodontitis.
PMID- 28686093
TI - Niobium pentoxide phosphate invert glass as a mineralizing agent in an
experimental orthodontic adhesive.
AB - OBJECTIVE: The aim of this study was to develop an experimental orthodontic
adhesive and evaluate how adding phosphate invert glass containing niobium
pentoxide (PIG-Nb) affected the adhesive's properties. MATERIAL AND METHODS: PIG
Nb was added at 1, 2.5, and 5 wt% to experimental adhesive (75 wt% bisphenol A
methacrylate [BisGMA], 25 wt% triethylene glycol dimethacrylate [TEGDMA], 5 wt%
colloidal silica and photoinitiator system). The adhesives were evaluated for
mineral deposition, degree of conversion (DC), softening solvent by Knoop
microhardness (KNH) variation, pH changes, and shear bond strength (SBS). One-way
analysis of variance (ANOVA) (DC and DeltaKHN%), two-way ANOVA (SBS), repeated
measures ANOVA (pH), and paired test (KNH1 and KNH2) were used at a significance
level of P < .05. RESULTS: Adding PIG-Nb to orthodontic adhesives induced
deposition on its surface associated with a constant neutral pH. The SBS
increased after immersion in artificial saliva, and the PIG-Nb5 exhibited less
softening. CONCLUSION: The addition of PIG-Nb into orthodontic adhesives induced
mineral deposition. Experimental orthodontic adhesive containing 5% wt of PIG-Nb
exhibited increased mineral deposition and suitable properties for orthodontic
applications.
PMID- 28686094
TI - Influence of clinicians' experience and gender on extraction decision in
orthodontics.
AB - OBJECTIVE: To determine whether, in Class I borderline cases, experienced
orthodontists choose nonextraction treatment more frequently than do
orthodontists with less experience. A secondary aim was to evaluate whether
clinicians' gender and place of education play a role in extraction decision
making. MATERIALS AND METHODS: An online survey was developed using three Class I
borderline patient cases. The survey included questions about clinicians'
demographics as well as questions about the selected cases. The survey was
distributed to approximately 2000 clinicians through the American Association of
Orthodontics. RESULTS: Of the 253 responses collected, a trend was observed
wherein clinicians with more than 15 years of experience preferred an extraction
treatment option more frequently than did clinicians with less than 5 years of
experience. There was no association between gender and place of education and
the decision to extract in the selected borderline cases. Crowding, patient's
profile, and mandibular incisor inclination were among the top three reasons
chosen by clinicians for both the extraction and nonextraction treatment
decisions. CONCLUSIONS: A trend was observed in which clinicians with more
experience chose an extraction treatment option more frequently in borderline
cases than did those with less experience. Clinicians' gender did not play a role
in extraction decision making.
PMID- 28686095
TI - Does a Teaching Community Nursing Team have potential?
PMID- 28686096
TI - The Community Dental Service in Abertawe Bro Morgannwg University Health Board.
PMID- 28686097
TI - Being lonely and isolated: Challenges for palliative care.
PMID- 28686098
TI - The heat is on: Community nursing in the summer of 2017.
PMID- 28686099
TI - Perspectives on the risks for older adults living independently.
AB - Insight into risks concerning older adults living independently from their own
perspective and their care provider's perspective is essential to address issues
that may threaten their independent living. The most often mentioned perceived
risks by older adults and their care providers in different regions in the
Netherlands were: loneliness, falls, budget cuts in Dutch long-term care and not
being able to call for help. The different perspectives of the respondents show a
wide variety in risks, but also some similarities. The perspective of the frail
older adults is required to gain insight into the priority of their perceived
risks. An additional finding was the reluctance shown by the older adults to ask
others in their social network for help. Results imply that possible preventive
measures should not only focus on the medical or physical domain because older
adults are likely to have other priorities to maintain self-reliance and live
independently.
PMID- 28686100
TI - "Wandering" and dementia.
PMID- 28686101
TI - Pet dogs as promoters of wellbeing.
AB - The rise in life expectancy requires strategies to enable healthy ageing and the
promotion of a high quality of life in old age. Poor mental health including
depression and social isolation can blight older people's lives. Despite the
positive benefits of physical activity for both mental and physical health, only
a minority of those over 65 years are attaining the recommended levels of
physical activity. The evidence relating to the benefits of pet dogs as promoters
of wellbeing is set out in this article, although meeting their care needs may
place an additional strain on an older person and/or their carer who has limited
resources and physical capabilities.
PMID- 28686102
TI - Psychology in the community: An inherent part of nursing care.
PMID- 28686103
TI - Reporting deaths to the coroner.
AB - The Chief Coroner has issued new guidance in relation to death where the person
is subject to a deprivation of liberty safeguards standard authorisation ( Chief
Coroner, 2017 ). In this article, Richard Griffith discusses the impact of the
Police and Crime Act 2017, section 178 on the need to report deaths of patients'
subject to a deprivation of liberty safeguards standard authorisation to the
coroner.
PMID- 28686104
TI - Chelsea, Pimlico and Belgravia District Nursing Association 1930-1939: A case
study.
AB - The case study explores how the expansion of the health services during the
interwar period impacted upon the status of district nursing and examines how
being a voluntary service shaped district nursing associations. A range of
primary sources were used; the Association Annual Reports, the Medical Officer
for Health Annual Reports for the Borough of Chelsea, the Ministry of Health
records, the archives of the Queen's Nursing Institute (QNI) and the Borough of
Chelsea Council Minutes. The Medical Officer for Health Reports and the Council
minutes identify efforts to improve environmental factors that impacted upon
health. These primary sources briefly note the contribution of the Association
suggesting that it was integral to the health care provision but considered a
constant. The impact of changes to the 1932 Sunday Entertainments Act provide an
interesting juxtaposition between the acknowledged value of district nursing and
the constant struggle to fundraise in order to provide home nursing. Throughout
the 1930s the Association experienced staff shortages and challenges regarding
recruitment. The complexities of payment for municipal health services following
the 1929 Local Government Act contributed to the staffing challenges. The move to
a block grant in 1938 provided increased stability with regards to income. The
case study identifies a contradiction regarding the esteem and value placed upon
district nursing associations providing home nursing and the constant challenge
of resources. District nursing services face similar challenges and this is the
130th anniversary of the Queen's Nursing Institute.
PMID- 28686105
TI - Making a choice of catheterisation gel and the role of chlorhexidine.
AB - It is estimated that over 90 000 people in the UK community live with an
indwelling catheter ( Wilson, 2016 ). It is essential that a lubricating gel is
used during catheterisation, as this helps to reduce the risk of pain, trauma and
infection ( Loveday et al, 2014 ; National Institute for Health and Care
Excellence, 2012 ). Chlorhexidine is an antiseptic contained in many
catheterisation gels. Evidence demonstrates that increasing numbers of patients
are experiencing hypersensitivity reactions to this ingredient ( Australian and
New Zealand College of Anaesthetists, 2014 ). This article considers the range of
catheterisation gel choices available to clinicians and the importance of
selecting the correct gel for each patient. It addresses the benefits of using
OptiLube Active CHG Free (with lidocaine 2%) - the only catheterisation gel
currently available in the UK that contains the benefits of local anaesthetic
without chlorhexidine - and recommends that this should be the gel of choice for
non-specialist staff conducting catheterisations without individual patient
assessments.
PMID- 28686106
TI - Neonatal screening improves sickle cell disease clinical outcome in Belgium.
AB - Objectives To compare the outcomes of sickle cell disease patients diagnosed
through neonatal screening with those who were not. Methods In an observational
multicenter study in Belgium, 167 screened and 93 unscreened sickle cell disease
patients were analyzed for a total of 1116 and 958 patient-years of follow-up,
respectively. Both groups were compared with propensity score analysis, with
patients matched on three covariates (gender, genotype, and central Africa
origin). Bonferroni correction was applied for all comparisons. Results Kaplan
Meier estimates of survival without bacteremia were significantly higher in the
screened group than the unscreened group (94.47%; [95% CI, 88.64-97.36%] versus
83.78% [95% CI, 72.27-90.42%]), p = 0.032. Non-significant differences between
both groups were reported for survival without acute chest syndrome, acute
anemia, cerebral complication, severe infection, and vaso-occlusive crisis.
Significantly lower hospitalization rate and days per 100 patient-years were
observed in the screened compared with the unscreened group (0.27 vs. 0.63 and
1.25 vs. 2.82, p = 0.0006 and <0.0001). Conclusion These data confirm the benefit
of a neonatal screening programme in reducing bacteremia and hospitalization.
PMID- 28686107
TI - Critical exploration of co-occurring Attention-Deficit/Hyperactivity Disorder,
mood disorder and Substance Use Disorder.
AB - INTRODUCTION: Co-occurring disorders (CODs) describe a Substance Use Disorder
(SUD) accompanied by a comorbid psychiatric disorder. Attention
Deficit/Hyperactivity Disorder (ADHD) and mood disorders are common CODs with
high prevalence rates in SUD populations. It is proposed that literature on a tri
condition presentation of ADHD, mood disorder and SUD is limited. Areas covered:
A literature search was conducted using a keyword search on EBSCOhost. Initially
2 799 records were identified, however, only two articles included all three
conditions occurring concurrently in individuals. CODs constitute a major concern
due to their overarching burden on society as a whole. Diagnosis and treatment of
such patients is challenging. There is evidence that dysfunction of dopamine in
the brain reward circuitry impacts the development or symptomology of all three
disorders. Disparity exists regarding whether ADHD or mood disorders are greater
modifiers for increased SUD severity. However, it has been reported that poor
functional capacity may have a greater influence than comorbidities on SUD
development. Expert commentary: Challenges exist which confound the clear
distinction of CODs, however, with greater emergence of adult ADHD its screening
in SUD populations should become standard practice to establish data on multi
condition presentations with the ultimate goal of improving clinical outcomes.
PMID- 28686108
TI - The role of human urotensin-II in patients with hypertrophic cardiomyopathy.
AB - OBJECTIVE: Hypertrophic cardiomyopathy (HCM) is a genetic condition with the
hallmark feature of left ventricular hypertrophy. Human Urotensin-II (hUT-II) is
regarded as a cardiovascular autacoid/hormone, and it has cardiac inotropic and
hypertrophic properties. Aims of this study were to elucidate the clinical
significance of serum hUT-II levels as a potential new biomarker in patients with
HCM. METHODS: This study included 40 HCM patients (60% males and 40% females) and
were compared to 30 healthy control subjects (47% males and 53% females. All
patients underwent extensive clinical, laboratory, and echocardiographic. Blood
samples were taken to test for serum hUT-II levels by commercial ELISA Kit.
RESULTS: Serum hUT-II was significantly higher (p < 0.01) in patients with HCM
(15.8 +/- 2.1 pmol/L) compared with healthy controls (3.3 +/- 1.7 pmol/L). With
regard to HCM patient, Serum hUT-II levels were significantly higher in the
female with 16.3 +/- 1.9 pmol/L than the male with 15.4 +/- 2.2 pmol/L (p <
0.05). Among echocardiographic parameters, hUT-II was negatively associated with
ejection fraction (r = -0.160, p = 0.324). CONCLUSION: Results of the first study
indicated that serum hUT-II levels were markedly elevated in patients with HCM.
Serum hUT-II is a novel biomarker parameter that has clinical use in patients
with the severity of LVH.
PMID- 28686109
TI - alpha-Adducin gene promoter DNA methylation and the risk of essential
hypertension.
AB - This study was conducted to test the association between promoter DNA methylation
of alpha-Adducin (ADD1) gene and the risk of essential hypertension (EH). A total
of 150 EH patients and 100 aged- and gender-matched controls were investigated.
DNA methylation levels of five cytosine-phosphate-guanine (CpG) dinucleotides on
ADD1 promoter were measured employing bisulfite pyrosequencing technology. Our
results showed that females have a higher ADD1 DNA methylation than males and a
significantly lower CpG1 methylation level is associated with increased risk of
EH among them. As for males, a significant association between lower CpG2-5
methylation levels and increased risk of EH was shown. In addition, CpG2-5
methylation was found to be a highly significant predictor for EH among males. In
females, CpG1 methylation was considered a predictor of hypertension. No
significant correlations were found with biochemical measures, apart from the
concentration of aspartate aminotransferase which was inversely correlated with
ADD1 CpG2-5 methylation levels among female controls (r = -0.703). These findings
highlight that ADD1 methylation may have a contributing role in the pathogenesis
of EH with varying implications for both genders.
PMID- 28686110
TI - Role of endoscopic transnasal surgery for skull base chondrosarcoma: a
retrospective analysis of 19 cases at a single institution.
AB - OBJECTIVE Skull base chondrosarcoma is one of the most intractable tumors because
of its aggressive biological behavior and involvement of the internal carotid
artery and cranial nerves (CNs). One of the most accepted treatment strategies
for skull base chondrosarcoma has been surgical removal of the tumor in
conjunction with proactive extensive radiation therapy (RT) to the original tumor
bed. However, the optimal strategy has not been determined. The goal of this
study was to evaluate the early results of endoscopic transnasal surgery (ETS).
METHODS The authors retrospectively analyzed 19 consecutive patients who
underwent ETS at their institution since 2010. Adjuvant stereotactic radiosurgery
(SRS) was performed only for the small residual tumors that were not resected to
avoid critical neurological complications. Histological confirmation and
evaluation of the MIB-1 index was performed in all cases. The Kaplan-Meier method
was used to determine the actuarial rate of tumor-free survival. RESULTS The
median tumor volume and maximal diameter were 14.5 cm3 (range 1.4-88.4 cm3) and
3.8 cm (range 1.5-6.7 cm), respectively. Nine patients (47%) had intradural
extension of the tumor. Gross-total resection was achieved in 15 (78.9%) of the
19 patients, without any disabling complications. In 4 patients, the surgery
resulted in subtotal (n = 2, 11%) or partial (n = 2, 11%) resection because the
tumors involved critical structures, including the basilar artery or the lower
CNs. These 4 patients were additionally treated with SRS. The median follow-up
duration was 47, 28, and 27 months after the diagnosis, ETS, and SRS,
respectively. In 1 patient with an anterior skull base chondrosarcoma, the tumor
relapsed in the optic canal 1 year later and was treated with a second ETS.
Favorable tumor control was achieved in all other patients. The actuarial tumor
control rate was 93% at 5 years. At the final follow-up, all patients were alive
and able to perform independent activities of daily living without continuous
neurological sequelae. CONCLUSIONS These preliminary results suggest that ETS can
achieve sufficient radical tumor removal, resulting in comparative resection
rates with fewer neurological complications to those in previous reports.
Although the follow-up periods of these cases were relatively short, elective SRS
to the small tumor remnant may be rational, achieving successful tumor control in
some cases, instead of using proactive extensive RT. Thus, the addition of RT
should be discussed with each patient, after due consideration of histological
grading and biological behavior. To determine the efficacy of this strategy, a
larger case series with a longer follow-up period is essential. However, this
strategy may be able to establish evidence in the management of skull base
chondrosarcoma, providing less-invasive and effective options as an initial step
of treatment.
PMID- 28686111
TI - Delayed treatment of ruptured brain AVMs: is it ok to wait?
AB - OBJECTIVE Despite a hemorrhagic presentation, many patients with arteriovenous
malformations (AVMs) do not require emergency resection. The timing of definitive
management is not standardized in the cerebrovascular community. This study was
designed to evaluate the safety of delaying AVM treatment in clinically stable
patients with a new hemorrhagic presentation. The authors examined the rate of
rehemorrhage or neurological decline in a cohort of patients with ruptured brain
AVMs during a period of time posthemorrhage. METHODS Patients presenting to the
authors' institution from January 2000 to December 2015 with ruptured brain AVMs
treated at least 4 weeks posthemorrhage were included in this analysis. Exclusion
criteria were ruptured AVMs that required emergency surgery involving resection
of the AVM, prior treatment of AVM at another institution, or treatment of
lesions within 4 weeks for other reasons (subacute surgery). The primary outcome
measure was time from initial hemorrhage to treatment failure (defined as
rehemorrhage or neurological decline as a direct result of the AVM). Patient-days
were calculated from the day of initial rupture until the day AVM treatment was
initiated or treatment failed. RESULTS Of 102 ruptured AVMs in 102 patients
meeting inclusion criteria, 7 (6.9%) failed the treatment paradigm. Six patients
(5.8%) had a new hemorrhage within a median of 248 days (interquartile range 33
1364 days). The total "at risk" period was 18,740 patient-days, yielding a
rehemorrhage rate of 11.5% per patient-year, or 0.96% per patient-month. Twelve
(11.8%) of 102 patients were found to have an associated aneurysm. In this group
there was a single (8.3%) new hemorrhage during a total at-risk period of 263
patient-days until the aneurysm was secured, yielding a rehemorrhage risk of
11.4% per patient-month. CONCLUSIONS It is the authors' practice to rehabilitate
patients after brain AVM rupture with a plan for elective treatment of the AVM.
The present data are useful in that the findings quantify the risk of the
authors' treatment strategy. These findings indicate that delaying intervention
for at least 4 weeks after the initial hemorrhage subjects the patient to a low
(< 1%) risk of rehemorrhage. The authors modified the treatment paradigm when a
high-risk feature, such as an associated intracranial aneurysm, was identified.
PMID- 28686112
TI - Emergency resection of brainstem cavernous malformations.
AB - Brainstem cavernous malformations (CMs) pose significant challenges to
neurosurgeons because of their deep locations and high surgical risks. Most
patients with brainstem CMs present with sudden-onset cranial nerve deficits or
ataxia, but uncommonly patients can present in extremis from an acute hemorrhage,
requiring surgical intervention. However, the timing of surgery for brainstem CMs
has been a controversial topic. Although many authors propose delaying surgery
into the subacute phase, some patients may not tolerate waiting until surgery. To
the best of the authors' knowledge, emergency surgery after a brainstem CM
hemorrhage has not been described. In cases of rapidly progressive neurological
deterioration, emergency resection may often be the only option. In this
retrospectively reviewed small series of patients, the authors report favorable
outcomes after emergency surgery for resection of brainstem CMs.
PMID- 28686114
TI - Erratum. Reliability assessment of the Biffl Scale for blunt traumatic
cerebrovascular injury as detected on computer tomography angiography.
PMID- 28686115
TI - Letter to the Editor. Biffl Scale for blunt traumatic cerebrovascular injury.
PMID- 28686113
TI - Effects of different surgical modalities on the clinical outcome of patients with
moyamoya disease: a prospective cohort study.
AB - OBJECTIVE Bypass surgery is the most common treatment for moyamoya disease (MMD),
but there is controversy over which surgical modality is best. The objective of
this study was to evaluate the clinical outcome of patients with MMD after
undergoing different surgical modalities. METHODS A series of 696 consecutive MMD
patients treated between June 2009 and May 2015 were screened in this prospective
cohort study. Patients who did not undergo revascularization surgeries and those
who underwent different surgical modalities in bilateral hemispheres were
excluded. Finally, 529 patients who were observed for at least 12 months were
included: 438 patients underwent unilateral surgery, and 91 patients underwent
bilateral surgery. Of these, 241 patients underwent direct bypass (DB); 81, a
combined bypass (CB); and 207, an indirect bypass (IB). Three clinical outcomes
were evaluated and compared between surgical groups: recurrent stroke events,
modified Rankin Scale (mRS) scores, and change in the main symptoms. RESULTS The
mean follow-up period was 40 months. During the follow-up period, recurrent
stroke was observed in 43 patients, including 15 patients with hemorrhage, 26
patients with ischemia (transient ischemic attack in 19 patients and infarction
in 7 patients), and 2 patients with both hemorrhage and cerebral infarction.
Kaplan-Meier analysis showed that patients who underwent a CB or DB had a longer
ischemia-free time than those who underwent IB (p = 0.013); however, there was no
significant difference in the hemorrhage-free time between the different surgical
modalities (p = 0.534). A good neurological status (mRS score <= 2) was achieved
in 495 patients (93.6%) and was significantly achieved by more children (98.2%)
than adults (92.3%; p = 0.022). Surgical modalities were not significantly
associated with outcome neurological status (p = 0.860). Moreover, improvement in
symptoms was observed in 449 patients (84.9%) and was also significantly more
common in children (93.0%) than in adults (82.7%; p = 0.006). No significant
difference was observed between the different surgical modalities (p = 0.548).
CONCLUSIONS CB and DB are more effective at preventing recurrent ischemic strokes
than IB. However, there is no evidence that these 3 surgical modalities
demonstrate significant differences in preventing recurrent hemorrhage.
PMID- 28686116
TI - Clinical, radiological, and histological features and treatment outcomes of
supratentorial extraventricular ependymoma: 14 cases from a single center.
AB - OBJECTIVE Reports on supratentorial extraventricular ependymoma (STE) are
relatively rare. The object of this study was to analyze the clinical,
radiological, and histological features and treatment outcomes of 14 patients
with STE. METHODS Overall, 227 patients with ependymoma underwent surgical
treatment in the authors' department between January 2010 and June 2015; 14 of
these patients had STE. Data on clinical presentation, radiological studies,
histopathological findings, surgical strategies, and treatment outcomes in these
14 cases were retrospectively analyzed. RESULTS The patients consisted of 6 women
and 8 men (sex ratio 0.75). Mean age at diagnosis was 24.5 +/- 13.5 years (range
3-48 years). Tumors were predominantly located in the frontal and temporal lobes
(5 and 4 cases, respectively). Typical radiological features were mild to
moderate heterogeneous tumor enhancements on contrast-enhanced MRI. Other
radiological features included well-circumscribed, "popcorn" enhancement and no
distinct adjoining brain edema. Gross-total resection was achieved in 12
patients, while subtotal removal was performed in 2. Radiotherapy was
administered in 7 patients after surgery. Seven tumors were classified as WHO
Grade II and the other 7 were verified as WHO Grade III. The mean follow-up
period was 22.6 months (range 8-39 months). There were 3 patients with
recurrence, and 2 of these patients died. CONCLUSIONS Supratentorial
extraventricular ependymoma has atypical clinical presentations, various
radiological features, and heterogeneous histological forms; therefore,
definitive diagnosis can be difficult. Anaplastic STE shows malignant biological
behavior, a higher recurrence rate, and a relatively poor prognosis. Gross-total
resection with or without postoperative radiotherapy is currently the optimal
treatment for STE.
PMID- 28686117
TI - Predicting ischemic stroke after carotid artery stenting based on proximal
calcification and the jellyfish sign.
AB - OBJECTIVE Carotid artery stenting (CAS) has been considered to prevent ischemic
strokes caused by stenosis of the cervical carotid artery. The most common
complication of CAS is new cerebral infarction. The authors have previously
reported that the jellyfish sign-the rise and fall of the mobile component of the
carotid plaque surface detected by carotid ultrasonography-suggests thinning and
rupture of the fibrous cap over the unstable plaque content, such as the lipid
rich necrotic core or internal plaque hemorrhage. The authors' aim in the present
study was to evaluate the risk of a new ischemic lesion after CAS by using many
risk factors including calcification (size and location) and the jellyfish sign.
METHODS Eighty-six lesions (77 patients) were treated with CAS. The presence of
ischemic stroke was determined using diffusion-weighted imaging (DWI). Risk
factors included calcification of the plaque (classified into 5 groups for size
and 3 groups for location) and the jellyfish sign, among others. Multiple linear
regression analysis (stepwise analysis and partial least squares [PLS] analysis)
was conducted, followed by a machine learning analysis using an artificial neural
network (ANN) based on the log-linearized gaussian mixture network (LLGMN). The
additive effects of the jellyfish sign and calcification on ischemic stroke after
CAS were examined using the Kruskal-Wallis test, followed by the Steel-Dwass
test. RESULTS The stepwise analysis selected the jellyfish sign, proximal
calcification (proximal Ca), low-density lipoprotein (LDL) cholesterol, and
patient age for the prediction model to predict new DWI lesions. The PLS analysis
revealed the same top 3 variables (jellyfish sign, proximal Ca, and LDL
cholesterol) according to the variable importance in projection scores. The ANN
was then used, showing that these 3 variables remained. The accuracy of the ANN
improved; areas under the receiver operating characteristic curves of the
stepwise analysis, the PLS analysis, and the ANN were 0.719, 0.727, and 0.768,
respectively. The combination of the jellyfish sign and proximal Ca indicates a
significantly increased risk for ischemic stroke after CAS. CONCLUSIONS The
jellyfish sign, proximal Ca, and LDL cholesterol were considered to be important
predictors for new DWI lesions after CAS. These 3 factors can be easily
determined during a standard clinical visit. Thus, these 3 variables-especially
the jellyfish sign and proximal Ca-may be useful for reducing the ischemic stroke
risk in patients with stenosis of the cervical carotid artery.
PMID- 28686118
TI - Method for temporal keyhole lobectomies in resection of low- and high-grade
gliomas.
AB - OBJECTIVE The purpose of this study was to describe a method of resecting
temporal gliomas through a keyhole lobectomy and to share the results of using
this technique. METHODS The authors performed a retrospective review of data
obtained in all patients in whom the senior author performed resection of
temporal gliomas between 2012 and 2015. The authors describe their technique for
resecting dominant and nondominant gliomas, using both awake and asleep keyhole
craniotomy techniques. RESULTS Fifty-two patients were included in the study.
Twenty-six patients (50%) had not received prior surgery. Seventeen patients
(33%) were diagnosed with WHO Grade II/III tumors, and 35 patients (67%) were
diagnosed with a glioblastoma. Thirty tumors were left sided (58%). Thirty
procedures (58%) were performed while the patient was awake. The median extent of
resection was 95%, and at least 90% of the tumor was resected in 35 cases (67%).
Five of 49 patients (10%) with clinical follow-up experienced permanent deficits,
including 3 patients (6%) with hydrocephalus requiring placement of a
ventriculoperitoneal shunt and 2 patients (4%) with weakness. Three patients
experienced early postoperative anomia, but no patients had a new speech deficit
at clinical follow-up. CONCLUSIONS The authors provide their experience using a
keyhole lobectomy for resecting temporal gliomas. Their data demonstrate the
feasibility of using less invasive techniques to safely and aggressively treat
these tumors.
PMID- 28686119
TI - Management of peripheral nerve sheath tumors: 17 years of experience at Toronto
Western Hospital.
AB - OBJECTIVE A surgical series of 201 benign and malignant peripheral nerve sheath
tumors (PNSTs) was assessed to characterize the anatomical and clinical
presentation of tumors and identify predictors of neurological outcome,
recurrence, and extent of resection. METHODS All surgically treated PNSTs from
the Division of Neurosurgery at Toronto Western Hospital from 1993 to 2010 were
reviewed retrospectively. Data were collected on patient demographics, clinical
presentation, surgical technique, extent of resection, postoperative neurological
outcomes, and recurrence. RESULTS One hundred seventy-five patients with 201
tumors had adequate follow-up for analysis. There were 182 benign and 19
malignant PNSTs. Of the benign lesions, 133 were schwannomas, 21 of which were
associated with a diagnosis of schwannomatosis. There were 49 neurofibromas, and
26 were associated with neurofibromatosis Type 1 (NF1). Patients presenting with
schwannomas were significantly older than those with neurofibromas. Schwannomas
were more readily resected than neurofibromas, with the extent of resection of
the former influenced by tumor location. Patients with benign PNSTs typically
presented with a painful mass and less frequently with motor deficits. The
likelihood of worsened postoperative motor function was decreased in patients
with fully resected tumors or preoperative deficits. Recurrence of schwannomas
and neurofibromas were seen more frequently in patients diagnosed with NF3 and
NF1, respectively. Subtotal resection was associated with the increased
recurrence of all benign lesions. CONCLUSIONS Outcomes following resection of
benign PNSTs depend on tumor histopathology, tumor location, and genetic
predisposition syndrome. Gross-total resection should be attempted for benign
lesions where possible. The management of malignant PNSTs remains challenging,
requiring a multimodal approach.
PMID- 28686120
TI - Coincidence or complication? A systematic review of trigger digit after carpal
tunnel release.
AB - BACKGROUND: Carpal tunnel syndrome (CTS) and trigger digits are among the most
common nontraumatic hand disorders treated by plastic surgeons. The onset of
trigger digits after carpal tunnel release (CTR) has been inconsistently
reported. This systematic review assessed the prevalence of trigger digits
development in patients after CTR surgery. METHODS: We searched the MEDLINE,
EMBASE and SCOPUS databases for papers published between January 1966 and August
2016. Eligible studies contained quantitative data on the incidence of trigger
digits after CTR. The primary outcome measure was the onset of trigger digits
after CTR. The secondary outcome measure was the prevalence of digital
involvement in patients who developed trigger digits after CTR. RESULTS: A total
of 5654 CTR surgeries were performed in the included nine studies, and 483
patients (8.5%) developed trigger digits after CTR. The reported incidence of
trigger digits after CTR ranged from 5.2% to 31.7%. The time to development of
trigger digits was approximately 6 months postoperatively. In the eight
observational studies and in the randomized controlled trial, the thumb and ring
finger were reported as the most commonly involved trigger digits, respectively.
CONCLUSIONS: The incidence of trigger digits after CTR surgery is not negligible.
Thumbs and ring fingers are the most commonly involved digits. This topic should
therefore be suitably addressed during preoperative consultations.
PMID- 28686122
TI - Failure of ETV in patients with the highest ETV success scores.
AB - OBJECTIVE Endoscopic third ventriculostomy (ETV) is a surgical alternative to
placing a CSF shunt in certain patients with hydrocephalus. The ETV Success Score
(ETVSS) is a reliable, simple method to estimate the success of the procedure by
6 months of postoperative follow-up. The highest score is 90, estimating a 90%
chance of the ETV effectively treating hydrocephalus without requiring a shunt.
Treatment with ETV fails in certain patients, despite their being the
theoretically best candidates for the procedure. In this study the authors
attempted to identify factors that further predicted success in patients with the
highest ETVSSs. METHODS A retrospective review was performed of all patients
treated with ETV at 3 institutions. Demographic, radiological, and clinical data
were recorded. All patients by definition were older than 1 year, had obstructive
hydrocephalus, and did not have a prior shunt. Failure of ETV was defined as the
need for a shunt by 1 year. The ETV was considered a success if the patient did
not require another surgery (either shunt placement or a repeat endoscopic
procedure) by 1 year. A statistical analysis was performed to identify factors
associated with success or failure. RESULTS Fifty-nine patients met the entry
criteria for the study. Eleven patients (18.6%) required further surgery by 1
year. All of these patients received a shunt. The presenting symptom of lethargy
statistically correlated with success (p = 0.0126, odds ratio [OR] = 0.072). The
preoperative radiological finding of transependymal flow (p = 0.0375, OR 0.158)
correlated with success. A postoperative larger maximum width of the third
ventricle correlated with failure (p = 0.0265). CONCLUSIONS The preoperative
findings of lethargy and transependymal flow statistically correlated with
success. This suggests that the best candidates for ETV are those with a
relatively acute elevation of intracranial pressure. Cases without these findings
may represent the failures in this highly selected group.
PMID- 28686121
TI - Surgical and molecular considerations in the treatment of pediatric
thalamopeduncular tumors.
AB - OBJECTIVE Thalamopeduncular tumors are a group of pediatric low-grade gliomas
that arise at the interface of the thalamus and brainstem peduncle. They
typically occur within the first 2 decades of life, presenting with progressive
spastic hemiparesis. Treatment strategies, including surgical intervention, have
varied significantly. The authors present their experience in the treatment of 13
children, ages 2-15 years, with non-neurofibromatosis-related pilocytic
astrocytomas located in the thalamopeduncular region. METHODS Between 2003 and
2016, 13 children presenting with progressive spastic hemiparesis due to a
pilocytic astrocytoma at the interface of the thalamus and cerebral peduncles
were identified. Medical records were reviewed retrospectively for clinical,
radiological, pathological, and surgical data. Formalin-fixed, paraffin-embedded
tissue was obtained for 12 cases and tested for KIAA1549-BRAF fusion and BRAF
V600E point mutation. RESULTS On preoperative diffusion tensor imaging
tractography (performed in 12 patients), the ipsilateral corticospinal tract was
displaced laterally in 1 case (8.3%), medially in 1 case (8.3%), anterolaterally
in 10 cases (83%), and posteriorly in no cases. Ten patients underwent resection
via a transtemporal, transchoroidal approach, which was chosen to avoid further
damage to motor function in cases of tumors that caused anterolateral or medial
corticospinal tract displacement. With this approach, complications included
hemianopia, oculomotor palsy, and tremor at a rate of 50%. Among the 12 patients
with obtainable follow-up (mean 50.9 months), none received adjuvant therapy, and
only 2 (17%) experienced recurrence or progression. KIAA1549-BRAF fusions were
present in 10 cases (83%), while BRAF V600E was absent (0%). The 2 fusion
negative tumors had clinical features atypical for the series, including multi
focality and infiltration. CONCLUSIONS Transcortical, transchoroidal resection of
thalamopeduncular tumors through the middle temporal gyrus allows for a high rate
of gross-total resection and cure. Diffuse tensor tractography is a critical
component of the preoperative planning process to determine the location of white
matter tracts in proximity. Molecular status may correlate with clinical
features, and the presence of BRAF lesions offers an additional target for future
novel therapeutics.
PMID- 28686123
TI - Open thoracic anterolateral cordotomy for pain relief in children: report of 2
cases.
AB - Open anterolateral cordotomy is an effective treatment option for adults with
intractable pain, but it has seldom been attempted in children. In the 2
previously reported cases in children, the procedure was used within 10 days of
death from neoplastic disease. In this paper the authors describe 2 cases in
which open cordotomy was used successfully in children outside the immediate
terminal phase of disease. Both patients experienced effective analgesia with
minimal adverse effects. The authors propose that consideration of cordotomy as
an option for the management of intractable pain in children does not need to be
delayed until death is imminent.
PMID- 28686124
TI - Influence of an intratumoral cyst on drug distribution by convection-enhanced
delivery: case report.
AB - Convection-enhanced delivery (CED) uses positive pressure to induce convective
flow of molecules and maximize drug distribution. Concerns have been raised about
the effect of cystic structures on uniform drug distribution with CED. The
authors describe the case of a patient with a diffuse intrinsic pontine glioma
(DIPG) with a large cyst and examine its effect on drug distribution after CED
with a radiolabeled antibody. The patient was treated according to protocol with
CED of 124I-8H9 to the pons for nonprogressive DIPG after radiation therapy as
part of a Phase I trial (clinical trial registration no. NCT01502917,
clinicaltrials.gov). Care was taken to avoid the cystic cavity in the planned
catheter track and target point. Co-infusion with Gd-DTPA was performed to assess
drug distribution. Infusate distribution was examined by MRI immediately
following infusion and analyzed using iPlan Flow software. Analysis of
postinfusion MR images demonstrated convective distribution around the catheter
tip and an elongated configuration of drug distribution, consistent with the
superoinferior corticospinal fiber orientation in the brainstem. This indicates
that the catheter was functioning and a pressure gradient was established. No
infusate entry into the cystic region could be identified on T2-weighted FLAIR or
T1-weighted images. The effects of ependymal and pial surfaces on drug delivery
using CED in brainstem tumors remain controversial. Drug distribution is a
critical component of effective application of CED to neurosurgical lesions. This
case suggests that cyst cavities may not always behave as fluid "sinks" for drug
distribution. The authors observed that infusate was not lost into the cyst
cavity, suggesting that lesions with cystic components can be treated by CED
without significant alterations to target and infusion planning.
PMID- 28686125
TI - Atypical choroid plexus papilloma: spontaneous resolution of diffuse
leptomeningeal contrast enhancement after primary tumor removal in 2 pediatric
cases.
AB - Atypical choroid plexus papillomas can metastasize in the form of leptomeningeal
seeding. Postoperative chemotherapy is the recommended first-line treatment when
gross-total removal is not achieved or in cases of disseminated disease. Here the
authors report on 2 children with atypical choroid plexus papillomas and MRI
findings of diffuse leptomeningeal enhancement at diagnosis, later presenting
with spontaneous resolution of the leptomeningeal involvement after removal of
the primary lesions. Observations in this report expand our knowledge about the
natural history and biological behavior of these tumors and highlight the role of
close neuroimaging surveillance in the management of atypical choroid plexus
papillomas in cases with MRI evidence of diffuse leptomeningeal enhancement at
presentation.
PMID- 28686126
TI - Impact of magnetic resonance imaging and urodynamic studies on the management of
sacrococcygeal dimples.
AB - OBJECTIVE Sacrococcygeal dimples in neonates and infants are of uncertain
pathological import. Previously they were believed to be rarely associated with
intraspinal anomalies. Recent studies using MRI, however, revealed that 6%-7% of
pediatric cases of sacrococcygeal dimples were associated with anatomical
tethered spinal cord (TSC). Because the prevalence of tethered cord syndrome is
still unclear, there is no consensus among pediatric neurosurgeons on the
management of children with sacrococcygeal dimples. The authors performed an
analysis of MRI and urodynamic studies to validate their management strategy for
pediatric cases of sacrococcygeal dimples. METHODS A total of 103 Japanese
children (49 male and 54 female, median age 4 months, range 8 days-83 months)
with sacrococcygeal dimples who were referred to the Division of Pediatric
Neurosurgery between 2013 and 2015 were included in this study. The lumbosacral
region of all the patients was investigated using MRI. Anatomical TSC was defined
as a condition in which the caudal end of the conus medullaris is lower than the
inferior border of the L2-3 intervertebral disc. Patients with minor spinal
anomalies (e.g., anatomical TSC, filum lipoma, thickened filum, or filar cyst)
underwent further urodynamic studies to ascertain the presence of neurogenic
bladder (NGB). In this study, the presence of NGB without anatomical TSC but with
other minor spinal anomalies was defined as "functional TSC." The prevalence of
anatomical and functional TSC was investigated. The association of the following
cutaneous findings with spinal anomalies was also assessed: 1) depth of the
dimple, 2) deviation of the gluteal fold, and 3) other skin abnormalities (e.g.,
discoloration, angioma, or abnormal hair). RESULTS The children were classified
into 4 groups: Group 1, patients with anatomical TSC; Group 2, patients with
functional TSC; Group 3, patients without anatomical or functional TSC but with
other minor spinal anomalies; and Group 4, patients with no spinal anomaly. There
were 6 patients (5.8%) in Group 1, 8 patients (7.8%) in Group 2, 10 patients
(9.7%) in Group 3, and 79 patients (76.7%) in Group 4. Twenty-four patients
(23.3%; Groups 1, 2, and 3) showed MRI abnormalities, including filum lipoma (14
cases), filar cysts (5 cases), thickened filum (2 cases), and anatomical TSC
without other spinal anomalies (3 cases). Untethering of the spinal cord was
indicated for 14 patients (13.6%; Groups 1 and 2) with anatomical and functional
TSCs. Preoperative NGB was found in 12 patients and improved postoperatively in 7
(58.3%). None of the associated lumbosacral skin findings predicted the presence
of underlying spinal anomalies. CONCLUSIONS The prevalence of tethered cord
syndrome among children with sacrococcygeal dimples was, for the first time,
revealed to be higher than previously thought. MRI and supplemental urodynamic
studies may be indicated for children with sacrococcygeal dimples to identify
patients with symptomatic TSC.
PMID- 28686127
TI - Effectiveness of surgical revascularization for stroke prevention in pediatric
patients with sickle cell disease and moyamoya syndrome.
AB - OBJECTIVE Sickle cell disease (SCD) in combination with moyamoya syndrome (MMS)
represents a rare complication of SCD, with potentially devastating neurological
outcomes. The effectiveness of surgical revascularization in this patient
population is currently unclear. The authors' aim was to determine the
effectiveness of surgical intervention in their series of SCD-MMS patients by
comparing stroke recurrence in those undergoing revascularization and those
undergoing conservative transfusion therapy. METHODS The authors performed a
retrospective chart review of patients with MMS who were seen at the Johns
Hopkins Medical Institution between 1990 and 2013. Pediatric patients (age < 18
years) with confirmed diagnoses of SCD and MMS were included. Intracranial stroke
occurrence during the follow-up period was compared between surgically and
conservatively managed patients. RESULTS A total of 15 pediatric SCD-MMS patients
(28 affected hemispheres) were included in this study, and all were African
American. Seven patients (12 hemispheres) were treated with indirect surgical
revascularization. The average age at MMS diagnosis was 9.0 +/- 4.0 years, and 9
patients (60.0%) were female. Fourteen patients (93.3%) had strokes before
diagnosis of MMS, with an average age at first stroke of 6.6 +/- 3.9 years.
During an average follow-up period of 11.6 years, 4 patients in the conservative
treatment group experienced strokes in 5 hemispheres, whereas no patient
undergoing the revascularization procedure had any strokes at follow-up (p =
0.029). Three patients experienced immediate postoperative transient ischemic
attacks, but all recovered without subsequent strokes. CONCLUSIONS Indirect
revascularization is suggested as a safe and effective alternative to the best
medical therapy alone in patients with SCD-MMS. High-risk patients managed on a
regimen of chronic transfusion should be considered for indirect
revascularization to maximize the effect of stroke prevention.
PMID- 28686128
TI - Healthcare managers' perception of economies of scale.
AB - Purpose The purpose of this paper is to explore how healthcare managers perceive
economies of scale and the underlying mechanisms for how scale/size affects
performance. Design/methodology/approach Data were collected in 20 in-depth
interviews with healthcare professionals from 13 healthcare delivery
organizations and from a public authority that finances and contracts healthcare
services. Data were coded and analysed using content analysis. Findings The study
concludes that the impact of scale on performance is perceived by healthcare
professionals to be different for different types of healthcare services: For
surgery, significant scale effects related to spreading of fixed cost, the
experience curve, and potential for process improvement. For inpatient care,
moderate scale effects related to spreading of fixed costs and costs of doctors
on on-call duty. For outpatient care, small or no scale effects. Research
limitations/implications The small sample of interviewees from a single
geographical region and healthcare system limits the applicability of the
findings. Originality/value The paper provides insights into how healthcare
managers experience scale effects and how they consider economies of scale when
planning hospital configuration. Also, past studies of economies of scale in
hospitals proffer mixed results and the findings in this paper indicate a
possible explanation for this inconclusiveness, i.e. differences in service mix
between different hospitals.
PMID- 28686129
TI - Centres for Leadership: a strategy for academic integration.
AB - Purpose The purpose of this paper is to describe how an Academic Health Science
Centre, providing pediatric rehabilitation services, research, and education,
developed a Centres for Leadership (CfL) initiative to integrate its academic
functions and embrace the goal of being a learning organization.
Design/methodology/approach Historical documents, tracked output information, and
staff members' insights were used to describe the ten-year evolution of the
initiative, its benefits, and transformational learnings for the organization.
Findings The evolutions concerned development of a series of CfLs, and changes
over time in leadership and management structure, as well as in operations and
targeted activities. Benefits included enhanced clinician engagement in research,
practice-based research, and impacts on clinical practice. Transformational
learnings concerned the importance of supporting stakeholder engagement,
fostering a spirit of inquiry, and fostering leaderful practice. These learnings
contributed to three related emergent outcomes reflecting "way stations" on the
journey to enhanced evidence-informed decision making and clinical excellence:
enhancements in authentic partnerships, greater innovation capacity, and greater
understanding and actualization of leadership values. Practical implications
Practical information is provided for other organizations interested in
understanding how this initiative evolved, its tangible value, and its wider
benefits for organizational collaboration, innovation, and leadership values.
Challenges encountered and main messages for other organizations are also
considered. Originality/value A strategy map is used to present the structures,
processes, and outcomes arising from the initiative, with the goal of informing
the operations of other organizations desiring to be learning organizations.
PMID- 28686130
TI - Hospital performance dashboards: a literature review.
AB - Purpose The purpose of this paper is to give a comprehensive and updated analysis
of the available literature on hospital dashboards. Design/methodology/approach A
search of the current literature was performed by searching electronic databases,
including Google Scholar, EBSCO and Medline, as well as books. Findings In all,
48 manuscripts consisting of peer reviewed articles, conference proceedings, case
reports and text books were included in this review. Practical implications
Despite the numerous advantages of performance dashboards, several authors have
mentioned a number of challenges. It was evident from the literature that any
setting requires significant effort, especially to ensure the quality of data
being collected. In fact, significant investment, both in terms of financial and
human resources, is required to achieve an effective dashboard. Furthermore, most
of the studies available in the literature were individual case reports or
anecdotal accounts rather than empirical studies. Thus, further research is
required to ascertain the effectiveness of performance dashboards. In view of
these findings, each organisation should make its own decisions whether or not to
adopt performance dashboards. Originality/value Most of the literature is
fragmented as it reports the use of different types of dashboards, namely
strategic, tactical and operational, as separate tools. This literature review
contributes to knowledge as it brings together the different types of dashboards
and the cascading effect of one dashboard onto another in order to achieve and
retain organisational alignment with the overall strategic goals.
PMID- 28686131
TI - Occupational health and safety management practices and musculoskeletal disorders
in aged care.
AB - Purpose The purpose of this paper is to examine whether occupational health and
safety (OHS) management used to manage musculoskeletal disorders (MSDs) in the
aged care sector reflects contemporary research evidence of best practice to
reduce the incidence of these disorders. Design/methodology/approach In total, 58
interviews were conducted with managers and supervisors in the aged care sector
across four organisations in Australia. Policies and procedures relating to MSDs
were reviewed for each organisation. Findings Policies and procedures for
managing MSDs do not reflect contemporary evidence, which supports a complex
aetiology, related to a range of physical and psychosocial workplace factors.
Despite strong evidence that psychosocial factors contribute to MSD development,
these were not included in the policies and procedures reviewed. Findings from
the interviews management practices including leadership and various components
of HRM were functioning well but fragmentation was evident due to the challenging
nature of the aged care sector. Practical implications To address the significant
burden of MSDs in the aged care sector, policies and procedures need to include
coverage of psychosocial and physical workplace factors. The development of
systematic and integrated OHS management at the workplace level may play an
important role in the effective management of MSDs. Originality/value This study
offers insights into the previously unexplored area of MSD risk management and
the role of management practices such as HRM in the aged care sector.
PMID- 28686132
TI - Organizing for teamwork in healthcare: an alternative to team training?
AB - Purpose The purpose of this paper is to explore how organizational design could
support teamwork and to identify organizational design principles that promote
successful teamwork. Design/methodology/approach Since traditional team training
sessions take resources away from production, the alternative approach pursued
here explores the promotion of teamwork by means of organizational design. A wide
and pragmatic definition of teamwork is applied: a team is considered to be a
group of people that are set to work together on a task, and teamwork is then
what they do in relation to their task. The input - process - output model of
teamwork provides structure to the investigation. Findings Six teamwork enablers
from the healthcare team literature - cohesion, collaboration, communication,
conflict resolution, coordination, and leadership - are discussed, and the
organizational design measures required to implement them are identified. Three
organizational principles are argued to facilitate the teamwork enablers: team
stability, occasions for communication, and a participative and adaptive approach
to leadership. Research limitations/implications The findings could be used as a
foundation for intervention studies to improve team performance or as a framework
for evaluation of existing organizations. Practical implications By implementing
these organizational principles, it is possible to achieve many of the
organizational traits associated with good teamwork. Thus, thoughtful
organization for teamwork can be used as an alternative or complement to the
traditional team training approach. Originality/value With regards to the vast
literature on team training, this paper offers an alternative perspective on how
to improve team performance in healthcare.
PMID- 28686133
TI - Rethinking compassion fatigue.
AB - Purpose The purpose of this paper is to argue for a revision of the concept of
compassion fatigue in light of both its history and psychodynamics.
Design/methodology/approach This paper calls into question conventional
interpretations of compassion fatigue and the assumptions underlying them. As an
alternative, a psychoanalytic interpretation is offered that sheds light on the
phenomenon's unconscious and organizational dynamics. This interpretation also
aligns with the concept's historical use in media and politics. Findings In
contrast to the assumption that compassion fatigue arises from too much
compassion, historical use of the term suggests just the opposite: compassion
fatigue is the result of too little compassion. Healthcare literature on
compassion fatigue has not only failed to account for this opposing view, but
also the underlying psychodynamics at play. By attending to these neglected
dimensions, healthcare scholars and practitioners can gain new insights into
compassion fatigue and devise more sustainable interventions. Originality/value
This paper reveals hidden dimensions to compassion fatigue that call into
question conventional interpretations and offer novel perspectives on a core
concern of healthcare work.
PMID- 28686134
TI - Can lean contribute to work intensification in healthcare?
AB - Purpose The purpose of this paper is to review and discuss the effects of the
introduction of lean into healthcare workplaces, phenomena that have not been
widely investigated. Design/methodology/approach The paper draws on discussions
and findings from the literature. It seeks to bring the few geographically
dispersed experiences and case studies together to draw some conclusions
regarding lean's negative effects. Findings Two recurring themes emerge. The
first is there is little evidence of Lean's impact on work and the people who
perform it. The literature therefore suggests that we understand very little
about how work conditions are changed and how Lean's negative effects arise and
may be managed in healthcare workplaces. A second observation is that Lean's
effects are ambiguous. For some Lean seems to intensify work, while for others it
leads to improved job satisfaction and productivity. Given this variety, the
paper suggests a research emphasis on Lean's socio-cultural side and to derive
more data on how work and its processes change, particularly in the context of
healthcare team-working. Originality/value The paper concludes that without
improved understanding of social contexts of Lean interventions its value for
healthcare improvement may be limited. Future research should also include a
focus on how the work is changed and whether high-performance work system
practices may be used to offset Lean's negative effects.
PMID- 28686135
TI - The link between UHC reforms and health system governance: lessons from Asia.
AB - Purpose The purpose of this paper is to examine how and to what extent the design
and implementation of universal health coverage (UHC) reforms have been
influenced by the governance arrangements of health systems in low- and middle
income countries (LMIC); and how governments in these countries have or have not
responded to the challenges of governance for UHC. Design/methodology/approach
Comparative case study analysis of three Asian countries with substantial
experience of UHC reforms (Thailand, Vietnam and China) was undertaken using data
from published studies and grey literature. Studies included were those which
described the modifications and adaptations that occurred during design and
implementation of the UHC programme, the actors and institutions involved and how
these changes related to the governance of the health system. Findings Each
country adapted the design of their UHC programmes to accommodate their specific
institutional arrangements, and then made further modifications in response to
issues arising during implementation. The authors found that these modifications
were often related to the impacts on governance of the institutional changes
inherent in UHC reforms. Governments varied in their response to these governance
impacts, with Thailand prepared to adopt new governance modes (which the authors
termed as an "adaptive" response), while China and Vietnam have tended to persist
with traditional hierarchical governance modes ("reactive" responses).
Originality/value This study addresses a gap in current knowledge on UHC reform,
and finds evidence of a complex interaction between substantive health sector
reform and governance reform in the LMIC context in Asia, confirming recent
similar observations on health reforms in high-income countries.
PMID- 28686136
TI - Workplace bullying in the Australian health context: a systematic review.
AB - Purpose During the past decade, there has been increased attention into bullying
behaviours in workplaces. Research to date has varied in design, the definition
of what constitutes bullying behaviour, as well as the methods used to collect
data and measure bullying incidence and prevalence. Nonetheless, studies
demonstrate that bullying is a significant issue, which warrants an increased
research focus to develop greater understanding of the concept, its effects and
implications in, and for, the workplace. The purpose of this paper is to focus on
capturing a range of international and Australian literature regarding workplace
bullying behaviours in a health context from a management perspective. As a
result, this paper identified the gaps in the literature when expanded
specifically to an Australian health context. Design/methodology/approach The
purpose of this review is to summarise the existing literature, both
internationally and in Australia which examines workplace bullying behaviours in
a health context from a management perspective. This describes the review of the
literature on workplace bullying in a health context undertaken from January to
April 2014. The "Preferred Reporting Systematic Reviews and Meta-Analyses" method
was used to structure the review, which covered a wide range of literature from
databases including MEDLINE, Embase, CINAHL and InformIT, as well as reports, and
grey literature. Findings The review included 62 studies that met the inclusion
criteria and reported either: factors contributing to workplace bullying, at
least one significant example of workplace bullying behaviour or the impact of
workplace bullying behaviours in a health context. Originality/value There is
limited data on workplace bullying behaviours in an Australian health context.
The literature supports there is value in future research to develop consistent
definitions, policies, procedures and frameworks, which could help to prevent or
address workplace bullying behaviours based on work being undertaken
internationally.
PMID- 28686137
TI - Using a Large-scale Neural Model of Cortical Object Processing to Investigate the
Neural Substrate for Managing Multiple Items in Short-term Memory.
AB - Many cognitive and computational models have been proposed to help understand
working memory. In this article, we present a simulation study of cortical
processing of visual objects during several working memory tasks using an
extended version of a previously constructed large-scale neural model [Tagamets,
M. A., & Horwitz, B. Integrating electrophysiological and anatomical experimental
data to create a large-scale model that simulates a delayed match-to-sample human
brain imaging study. Cerebral Cortex, 8, 310-320, 1998]. The original model
consisted of arrays of Wilson-Cowan type of neuronal populations representing
primary and secondary visual cortices, inferotemporal (IT) cortex, and pFC. We
added a module representing entorhinal cortex, which functions as a gating
module. We successfully implemented multiple working memory tasks using the same
model and produced neuronal patterns in visual cortex, IT cortex, and pFC that
match experimental findings. These working memory tasks can include distractor
stimuli or can require that multiple items be retained in mind during a delay
period (Sternberg's task). Besides electrophysiology data and behavioral data, we
also generated fMRI BOLD time series from our simulation. Our results support the
involvement of IT cortex in working memory maintenance and suggest the cortical
architecture underlying the neural mechanisms mediating particular working memory
tasks. Furthermore, we noticed that, during simulations of memorizing a list of
objects, the first and last items in the sequence were recalled best, which may
implicate the neural mechanism behind this important psychological effect (i.e.,
the primacy and recency effect).
PMID- 28686138
TI - Automatic Recruitment of the Motor System by Undetected Graspable Objects: A
Motor-evoked Potential Study.
AB - Previous behavioral and neuroimaging studies have suggested that the motor
properties associated with graspable objects may be automatically accessed when
people passively view these objects. We directly tested this by measuring the
excitability of the motor pathway when participants viewed pictures of graspable
objects that were presented during the attentional blink (AB), when items
frequently go undetected. Participants had to identify two briefly presented
objects separated by either a short or long SOA. Motor-evoked potentials were
measured from the right hand in response to a single TMS pulse delivered over the
left primary motor cortex 250 msec after the onset of the second target.
Behavioral results showed poorer identification of objects at short SOA compared
with long SOA, consistent with an AB, which did not differ between graspable and
nongraspable objects. However, motor-evoked potentials measured during the AB
were significantly higher for graspable objects than for nongraspable objects,
irrespective of whether the object was successfully identified or undetected.
This provides direct evidence that the motor system is automatically activated
during visual processing of objects that afford a motor action.
PMID- 28686139
TI - Neural Mechanisms Underlying Risk and Ambiguity Attitudes.
AB - Individual differences in attitudes to risk (a taste for risk, known
probabilities) and ambiguity (a tolerance for uncertainty, unknown probabilities)
differentially influence risky decision-making. However, it is not well
understood whether risk and ambiguity are coded differently within individuals.
Here, we tested whether individual differences in risk and ambiguity attitudes
were reflected in distinct neural correlates during choice and outcome processing
of risky and ambiguous gambles. To these ends, we developed a neuroimaging task
in which participants ( n = 50) chose between a sure gain and a gamble, which was
either risky or ambiguous, and presented decision outcomes (gains, no gains).
From a separate task in which the amount, probability, and ambiguity level were
varied, we estimated individuals' risk and ambiguity attitudes. Although there
was pronounced neural overlap between risky and ambiguous gambling in a network
typically related to decision-making under uncertainty, relatively more risk
seeking attitudes were associated with increased activation in valuation regions
of the brain (medial and lateral OFC), whereas relatively more ambiguity-seeking
attitudes were related to temporal cortex activation. In addition, although
striatum activation was observed during reward processing irrespective of a prior
risky or ambiguous gamble, reward processing after an ambiguous gamble resulted
in enhanced dorsomedial PFC activation, possibly functioning as a general signal
of uncertainty coding. These findings suggest that different neural mechanisms
reflect individual differences in risk and ambiguity attitudes and that risk and
ambiguity may impact overt risk-taking behavior in different ways.
PMID- 28686140
TI - An Analysis of the Complete Genome Sequence and Subgenomic RNAs Reveals Unique
Features of the Ampelovirus, Grapevine leafroll-associated virus 1.
AB - Despite being the first closterovirus documented in grapevines (Vitis sp.), the
molecular biology of Grapevine leafroll-associated virus 1 (GLRaV-1, genus
Ampelovirus, family Closteroviridae) is still in its infancy. In this study, the
complete genome sequence of two GLRaV-1 isolates was determined to be 18,731
(isolate WA-CH) and 18,946 (isolate WA-PN) nucleotides (nt). The genome of WA-CH
and WA-PN isolates encodes nine putative open reading frames (ORFs) and the
arrangement of these ORFs in both isolates was similar to that of Australian and
Canadian isolates. In addition to two divergent copies of the coat protein (CP),
the genome of GLRaV-1 isolates contain CP-homologous domain in four genes, making
the virus unique among Closteroviridae members. The 5' and 3' nontranslated
regions (NTRs) of WA-CH and WA-PN isolates showed differences in size and
sequence composition, with 5' NTR having variable number of ~65-nt-long repeats.
Using the 5' NTR sequences, a reverse transcription-polymerase chain reaction and
restriction fragment length polymorphism method was developed to distinguish
GLRaV-1 variants in vineyards. Northern analysis of total RNA from GLRaV-1
infected grapevine samples revealed three subgenomic RNAs (sgRNAs), corresponding
tentatively to CP, p21, and p24 ORFs, present at higher levels, with p24 sgRNA
observed at relatively higher abundance than the other two sgRNAs. The 5'
terminus of sgRNAs corresponding to CP, CPd1, CPd2, p21, and p24 were mapped to
the virus genome and the leader sequence for these five sgRNAs determined to be
68, 27, 15, 49, and 18 nt, respectively. Taken together, this study provided a
foundation for further elucidation of the comparative molecular biology of
closteroviruses infecting grapevines.
PMID- 28686141
TI - Educating patients and providers through comprehensive pharmacogenetic test
reports.
PMID- 28686142
TI - Care and supportive measures in school-aged children with prenatal substance
exposure.
AB - AIMS: Prenatal exposure to substances, including alcohol, opiates, and a number
of illicit drugs, may have a negative impact on fetal development. Studies have
shown that substance exposure can influence a child's neurodevelopment and the
need for care and supportive measures. In this study, we aimed to investigate the
care status and the level of supportive measures in school-aged children
prenatally exposed to alcohol and other substances. METHODS: This study included
children aged between 6 and 14 years who were referred to Haukeland University
Hospital in Norway with developmental impairment and a history of prenatal
substance exposure. Participants were classified according to their main prenatal
exposure to either alcohol or other substances. Information on care status and
supportive measures was obtained from medical records and participants'
caregivers. We also compared the use of supportive measures for children placed
into foster care before and after 1 year of age. RESULTS: A total of 111 (87% of
128 referrals) eligible children participated in the study. Of these 111
children, 96 (86%) were in foster care, of whom 29 (30%) were placed into foster
care during their first year of life and 83 out of 90 (92%) had supportive
measures, including reinforced foster care and school or social support.
CONCLUSIONS: A high proportion of the sample lived in foster care and received
supportive measures. Findings may reflect an increased need of care and support
in school-aged children with prenatal substance exposure, highlighting the
importance of awareness among caregivers and public agencies.
PMID- 28686143
TI - Pharmacogenetics of inflammatory bowel disease: a focus on Crohn's disease.
AB - Crohn's disease is an inflammatory bowel disease showing a high heterogeneity in
phenotype and a strong genetic component. The treatment is complex, due to
different severity of clinical parameters and to the fact that therapies only
permit to control symptoms and to induce remission for short periods. Moreover,
all categories of drugs present a great interindividual variability both in terms
of efficacy and side effects appearance. For this reason, the identification of
specific genomic biomarkers involved in drugs response will be of great clinical
utility in order to foresee drug's efficacy and to prevent adverse reactions,
permitting a more personalized therapeutic approach. In this review, we focus the
attention on the pharmacogenetic studies regarding drugs commonly utilized in
Crohn's disease treatment.
PMID- 28686145
TI - Minimally invasive dual iliac screw, dual rod fixation in a rare case of
pathological sacral fracture from a paraganglionoma: a technique description.
AB - The management of lumbosacral neoplastic disease can be demanding, often
requiring complex reconstruction. In the context of extensive sacral involvement,
the risk of iliac screw breakage is greater. Few studies advocate the use of dual
iliac screw techniques to reduce implant failure. In this report, the authors
have described the first case of percutaneous dual iliac screw, dual rod
insertion as part of a minimally invasive spinopelvic stabilization in a patient
with a sacral fracture from a paraganglionoma. The patient underwent percutaneous
L-2 to ilium fixation. A dual iliac screw, dual rod construct was used for
stabilizing the left lumbopelvic junction. At the 1-year follow-up, the patient
remained asymptomatic, with radiographs showing no signs of instrumentation
failure. Minimally invasive dual iliac screw, dual rod fixation is a viable
option in cases in which additional stability is required due to extensive
neoplastic disease or active individuals have increased functional demands. Short
term results in this report are encouraging; however, more research is warranted
to establish the procedure's long-term safety.
PMID- 28686144
TI - Synovial Fluid alpha-Defensin as a Biomarker for Peri-Prosthetic Joint Infection:
A Systematic Review and Meta-Analysis.
AB - BACKGROUND: Total joint arthroplasty (TJA) has been one of the most beneficial
interventions for treating patients suffering from joint disorders. However, peri
prosthetic joint infection (PJI) is a serious complication that often accompanies
TJA and the diagnosis of PJI is remains difficult. Questions remain regarding
whether certain biomarkers can be valuable in the diagnosis of PJI. PATIENTS AND
METHODS: We conducted our systematic review by searching PubMed, Embase, Web of
Science, the Cochrane Library, and Science Direct with the key words
"periprosthetic joint infection," "synovial fluid," and "alpha-defensin." Studies
that provided sufficient data to construct 2 * 2 contingency tables were chosen
based on inclusion and exclusion criteria. The quality of included studies was
assessed according to the revised Quality Assessment of Diagnostic Accuracy
Studies (QUADAS-2) criteria. The pooled sensitivity, specificity, and diagnostic
odds ratio (DOR) were calculated for the included studies. The summary receiver
operating characteristic (SROC) curve and the area under the summary receiver
operating characteristic (AUSROC) were used to evaluate the overall diagnostic
performance. RESULTS: Eight studies were included in this systematic review.
Among them four articles were included in meta-analysis. A total of 421
participants were studied in the meta-analysis. The pooled sensitivity,
specificity, and DOR were 0.98 (95% confidence interval [CI]: 0.94-1.00), 0.97
(95% CI: 0.95-0.99), and 1095.49 (95% CI: 283.68.58-4230.45), respectively. The
AUSROC was 0.9949 (standard error [SE] 0.0095). CONCLUSION: Synovial fluid alpha
defensin is a biomarker of high sensitivity and specificity for the diagnosis of
PJI.
PMID- 28686146
TI - Synovial cysts of the spine: long-term follow-up after surgical treatment of 141
cases in a single-center series and comprehensive literature review of 2900
degenerative spinal cysts.
AB - OBJECTIVE Synovial cysts of the spine are rare lesions, predominantly arising in
the lumbar region. Despite their generally benign behavior, they can cause severe
symptoms due to compression of neural structures in the spinal canal. Treatment
strategies are still a matter of discussion. The authors performed a single
center survey and literature search focusing on long-term results after minimally
invasive surgery. METHODS A total of 141 consecutive patients treated for
synovial cysts of the lumbar spine between 1997 and 2014 in the authors'
department were analyzed. Medical reports with regard to signs and symptoms,
operative findings, complications, and short-term outcome were reviewed.
Assessment of long-term outcome was performed with a standardized telephone
questionnaire based on the Oswestry Disability Index (ODI). Furthermore, patients
were questioned about persisting pain, symptoms, and further operative
procedures, if any. Subjective satisfaction was classified as excellent, good,
fair, or poor based on the Macnab classification. RESULTS The approach most often
used for synovial cyst treatment was partial hemilaminectomy in 70%;
hemilaminectomy was necessary in 27%. At short-term follow-up, the presence of
severe and moderate leg pain had decreased from 93% to 5%. The presence of low
back pain decreased from 90% to 5%. Rates of motor and sensory deficits were
reduced from 40% to 14% and from 45% to 6%, respectively. The follow-up rate was
58%, and the mean follow-up period was 9.3 years. Both leg pain and low-back pain
were still absent in 78%. Outcome based on the Macnab classification was
excellent in 80%, good in 14%, fair in 1%, and poor in 5%. According to the ODI,
78% of patients had no or only minimal disability, 16% had moderate disability,
and 6% had severe disability at the time of follow-up. In this cohort, 7% needed
surgery due to cyst recurrence, and 9% required a delayed stabilization procedure
after the initial operation. CONCLUSIONS Surgical treatment with resection of the
cyst provides favorable results in outcome. Excellent or good outcome persisting
for a long-term follow-up period can be achieved in the vast majority of cases.
Complication rates are low despite an increased risk of dural injury. With facet
sparing techniques, the stability of the segment can be preserved, and resection
of spinal synovial cysts does not necessarily require segmental fusion.
PMID- 28686148
TI - National Health and Nutrition Examination Survey: California and Los Angeles
County, Estimation Methods and Analytic Considerations, 1999-2006 and 2007-2014.
AB - Background California is the most populated state and Los Angeles County is the
most populated county in the United States. National Health and Nutrition
Examination Survey (NHANES) sample weights and variance units were developed for
these places to obtain subnational estimates. Objective This report describes the
California and Los Angeles County NHANES 1999-2006 and 2007-2014 samples,
including the creation of the sample weights and variance units and descriptions
of the resulting data files. Some analytic guidelines are provided. Results Eight
years of NHANES data were combined for each data file to provide an adequate
sample size and reduce disclosure risks. Because Los Angeles County has been a
self-representing primary sampling unit, sample weights for Los Angeles County
were relatively straightforward. However, a modelbased approach was used to
create sample weights for California. The relatively large proportion of Mexican-
American and other Hispanic persons in California, coupled with the different
NHANES 1999-2014 sample design requirements for oversampling these groups within
the small number of NHANES locations selected each cycle, led to a relatively
large size of these groups in the California and Los Angeles County NHANES files.
For example, 1,137 and 374 of the 3,353 Mexican-Americans persons in NHANES 2007
2014 were in the California and Los Angeles County samples, respectively.
Conclusion The California and Los Angeles County NHANES 1999-2006 and 2007-2014
samples are available in the National Center for Health Statistics Research Data
Center.
PMID- 28686147
TI - Surgical management of spinal osteoblastomas.
AB - OBJECTIVE Osteoblastoma is a rare primary benign bone tumor with a predilection
for the spinal column. Although of benign origin, osteoblastomas tend to behave
more aggressively clinically than other benign tumors. Because of the low
incidence of osteoblastomas, evidence-based treatment guidelines and high-quality
research are lacking, which has resulted in inconsistent treatment. The goal of
this study was to determine whether application of the Enneking classification in
the management of spinal osteoblastomas influences local recurrence and survival
time. METHODS A multicenter database of patients who underwent surgical
intervention for spinal osteoblastoma was developed by the AOSpine Knowledge
Forum Tumor. Patient data pertaining to demographics, diagnosis, treatment, cross
sectional survival, and local recurrence were collected. Patients in 2 cohorts,
based on the Enneking classification of the tumor (Enneking appropriate [EA] and
Enneking inappropriate [EI]), were analyzed. If the final pathology margin
matched the Enneking-recommended surgical margin, the tumor was classified as EA;
if not, it was classified as EI. RESULTS A total of 102 patients diagnosed with a
spinal osteoblastoma were identified between November 1991 and June 2012. Twenty
nine patients were omitted from the analysis because of short follow-up time,
incomplete survival data, or invalid staging, which left 73 patients for the
final analysis. Thirteen (18%) patients suffered a local recurrence, and 6 (8%)
patients died during the study period. Local recurrence was strongly associated
with mortality (relative risk 9.2; p = 0.008). When adjusted for Enneking
appropriateness, this result was not altered significantly. No significant
differences were found between the EA and EI groups in regard to local recurrence
and mortality. CONCLUSIONS In this evaluation of the largest multicenter cohort
of spinal osteoblastomas, local recurrence was found to be strongly associated
with mortality. Application of the Enneking classification as a treatment guide
for preventing local recurrence was not validated.
PMID- 28686149
TI - Enhanced opsonisation of Rhesus D-positive human red blood cells by recombinant
polymeric immunoglobulin G anti-G antibodies.
AB - BACKGROUND: Anti-RhD antibodies (anti-D) are important in the prophylaxis of
haemolytic disease of the foetus and newborn (HDFN) due to RhD incompatibility.
Current preparations of anti-D are sourced from hyperimmune human plasma, so its
production carries a risk of disease and is dependent on donor availability.
Despite the efforts to develop a monoclonal preparation with similar prophylactic
properties to the plasma-derived anti-D, no such antibody is yet available. Here
we studied the agglutinating, opsonic and haemolytic activities of two
recombinant polymeric immunoglobulins (Ig) against the G antigen of the Rh
complex. MATERIALS AND METHODS: Recombinant polymeric anti-G IgG1 (IgG1MUtp) and
IgG3 (IgG3MUtp) were produced in vitro, purified by protein G-affinity
chromatography, and analysed by gel electrophoresis. Their agglutinating, opsonic
and haemolytic activities were evaluated using haemagglutination,
erythrophagocytosis, and complement activation assays. RESULTS: The recombinant
IgG1MUtp and IgG3MUtp anti-G antibodies ranged from 150,000 to 1,000,000 Da in
molecular weight, indicating the formation of polymeric IgG. No complement
activation or haemolytic activity was detected upon incubation of RhD-positive
red-blood cells with the polymeric anti-G IgG. Both polymers were better opsonins
than a prophylactic preparation of plasma-derived anti-D. DISCUSSION: The
enhanced opsonic properties of the polymeric anti-G IgG1MUtp and IgG3MUtp could
allow them to mediate the clearance of RhD-positive red blood cells from
circulation more efficiently than natural or other synthetic prophylactic anti-D
options. Their inability to induce complement-mediated haemolysis would be
prophylactically convenient and is comparable in vitro to that of the available
plasma-derived polyclonal anti-D preparations. The described properties suggest
that polymeric antibodies like these (but with anti-D specificity) may be
testable candidates for prophylaxis of HDFN caused by anti-D.
PMID- 28686150
TI - Use of fresh-frozen plasma in 2012 at the Fondazione Ca' Granda Hospital of
Milan: assessment of appropriateness using record linkage techniques applied to
data routinely recorded in various hospital information systems.
AB - BACKGROUND: The Quality Unit of a research and teaching hospital in Milan
assessed the increased clinical use of fresh-frozen plasma in patients treated
during 2012 in order to evaluate the appropriateness of this use. MATERIALS AND
METHODS: For each patient in the study, a pathology profile was generated by
means of record linkage techniques involving data collected through different
information systems. Patients' information was combined using the patient
identifier key generating pathology profiles exported to an Excel file. The
profiles were reviewed by two haematologists who identified 101 potentially
inappropriate treatments for which the medical records had to be reviewed
manually. RESULTS: In 2012, 490 patients were transfused and for 473 cases the
automatic record linkage provided a complete profile. The information relating to
the remaining patients did not match, mainly because the patients underwent
outpatient procedures for which clinical information is not automatically
recorded. In the overall audit only 13 treatments were judged inappropriate.
DISCUSSION: Our study supports the view that record linkage techniques applied to
data routinely recorded in different hospital information systems could be
potentially extended to support clinical audits, enabling the generation of
automated patient profiles that can be easily evaluated, relegating manual checks
on medical records to doubtful cases only. Moreover, the method applied in this
study allows the analysis of a full set of cases instead of sample surveys,
increasing the robustness of the audit results.
PMID- 28686151
TI - Individual, contextual and network characteristics of blood donors and non
donors: a systematic review of recent literature.
AB - BACKGROUND: The ageing population and recent migration flows may negatively
affect the blood supply in the long term, increasing the importance of targeted
recruitment and retention strategies to address donors. This review sought to
identify individual, network and contextual characteristics related to blood
donor status and behaviour, to systematically discuss differences between study
results, and to identify possible factors to target in recruitment and retention
efforts. METHODS: The systematic review was conducted in accordance with a
predefined PROSPERO protocol (CRD42016039591). After quality assessments by
multiple independent raters, a final set of 66 peer-reviewed papers, published
between October 2009 and January 2017, were included for review. RESULTS:
Individual and contextual characteristics of blood donor status and behaviour
were categorised into five main lines of research: donor demographics,
motivations and barriers, adverse reactions and deferral, contextual factors, and
blood centre factors. Results on donor demographics, motivations and barriers,
and contextual factors were inconclusive, differing between studies, countries,
and sample characteristics. Adverse reactions and deferral were negatively
related to blood donor behaviour. Blood centre factors play an important role in
donor management, e.g., providing information, reminders, and (non-)monetary
rewards. No studies were found on network characteristics of (non-)donors.
DISCUSSION: Although individual and contextual characteristics strongly relate to
blood donor status and behaviour, mechanisms underlying these relations have not
been studied sufficiently. We want to stress the importance of longitudinal
studies in donor behaviour, exploring the role of life events and network
characteristics within blood donor careers. Increased understanding of donor
behaviour will assist policy makers of blood collection agencies, with the
ultimate goal of safeguarding a sufficient and matching blood supply.
PMID- 28686152
TI - Washing in hypotonic saline reduces the fraction of irreversibly-damaged cells in
stored blood: a proof-of-concept study.
AB - BACKGROUND: During hypothermic storage, a substantial fraction of red blood cells
(RBCs) transforms from flexible discocytes to rigid sphero-echinocytes and
spherocytes. Infusion of these irreversibly-damaged cells into the recipient
during transfusion serves no therapeutic purpose and may contribute to adverse
outcomes in some patients. In this proof-of-concept study we describe the use of
hypotonic washing for selective removal of the irreversibly-damaged cells from
stored blood. MATERIALS AND METHODS: Stored RBCs were mixed with saline of
various concentrations to identify optimal concentration for inducing osmotic
swelling and selective bursting of spherical cells (sphero-echinocytes,
spherocytes), while minimising indiscriminate lysis of other RBCs. Effectiveness
of optimal treatment was assessed by measuring morphology, rheological
properties, and surface phosphatidylserine (PS) exposure for cells from several
RBCs units (n=5, CPD>AS-1, leucoreduced, 6 weeks storage duration) washed in
hypotonic vs isotonic saline. RESULTS: Washing in mildly hypotonic saline (0.585
g/dL, osmolality: 221.7+/-2.3 mmol/kg) reduced the fraction of spherical cells 3
fold from 9.5+/-3.4% to 3.2+/-2.8%, while cutting PS exposure in half from 1.48+/
0.86% to 0.59+/-0.29%. Isotonic washing had no effect on PS exposure or the
fraction of spherical cells. Both isotonic and hypotonic washing increased the
fraction of well-preserved cells (discocytes, echinocytes 1) substantially, and
improved the ability of stored RBCs to perfuse an artificial microvascular
network by approximately 25%, as compared with the initial sample. DISCUSSION:
This study demonstrated that washing in hypotonic saline could selectively remove
a significant fraction of the spherical and PS-exposing cells from stored blood,
while significantly improving the rheological properties of remaining well
preserved RBCs. Further studies are needed to access the potential effect from
hypotonic washing on transfusion outcomes.
PMID- 28686153
TI - Heparin-like effect resistant to protamine in a child with haemorrhagic shock. Do
we need heparinase?
PMID- 28686155
TI - Paediatric venous thromboembolism: a report from the Italian Registry of
Thrombosis in Children (RITI).
AB - BACKGROUND: The Italian Registry of Thrombosis in Children (RITI) was established
by a multidisciplinary team with the aims of improving knowledge about neonatal
and paediatric thrombotic events in Italy and providing a preliminary source of
data for the future development of specific clinical trials and diagnostic
therapeutic protocols. MATERIALS AND METHODS: We analysed the subset of RITI data
concerning paediatric systemic venous thromboembolic events that occurred between
January 2007 and June 2013. RESULTS: Eighty-five deep venous thromboses and seven
pulmonary emboli were registered in the RITI. A prevalence peak was observed in
children aged 10 to 18 years and, unexpectedly, in children aged 1 to 5 years. A
central venous line was the main risk factor (55% of venous thromboembolic
events); surgery (not cardiac) (25%), concomitant infections (23%) and malignancy
(22%) were the clinical conditions most often associated with the onset of venous
thromboembolism. There was a diagnostic delay of more than 24 hours in 37% of the
venous thromboembolic events. Doppler ultrasound was the most widely used test
for the objective diagnosis of deep venous thrombosis (87%). Antithrombotic
therapy was administered in 96% of venous thromboembolic events, mainly low
molecular weight heparin (60%). In 2% of cases recurrences occurred, while post
thrombotic syndrome developed in 8.5% of cases. DISCUSSION: Although the data
from the RITI are largely in agreement with published data, peaks of prevalence
of thrombosis, risk factors and objective tests used for the diagnosis showed
some peculiarities which may deserve attention.
PMID- 28686154
TI - Influence of red blood cell-derived microparticles upon vasoregulation.
AB - Here we review recent data and the evolving understanding of the role of red
blood cell-derived microparticles (RMPs) in normal physiology and in disease
progression. Microparticles (MPs) are small membrane vesicles derived from
various parent cell types. MPs are produced in response to a variety of stimuli
through several cytoskeletal and membrane phospholipid changes. MPs have been
investigated as potential biomarkers for multiple disease processes and are
thought to have biological effects, most notably in: promotion of coagulation,
production and handling of reactive oxygen species, immune modulation,
angiogenesis, and in apoptosis. Specifically, RMPs are produced normally during
RBC maturation and their production is accelerated during processing and storage
for transfusion. Several factors during RBC storage are known to trigger RMP
production, including: increased intracellular calcium, increased potassium
leakage, and energy failure with ATP depletion. Of note, RMP composition differs
from that of intact RBCs, and the nature and composition of RMP components are
affected by both storage duration and the character of storage solutions.
Recognised RMP bioactivities include: promotion of coagulation, immune
modulation, and promotion of endothelial adhesion, as well as influence upon
vasoregulation via nitric oxide (NO) scavenging. Of particular relevance, RMPs
are more avid NO scavengers than intact RBCs and this feature has been proposed
as a mechanism for the impaired oxygen delivery homeostasis that has been
observed following transfusion. Preliminary human studies demonstrate that
circulating RMP abundance increases with RBC transfusion and is associated with
altered plasma vasoactivity and abnormal vasoregulation. In summary, RMPs are
submicron particles released from stored RBCs, with demonstrated vasoactive
properties that appear to disturb oxygen delivery homeostasis. The clinical
impact of RMPs in transfusion recipients is an area of continued investigation.
PMID- 28686156
TI - High-titre inhibitors in previously untreated patients with severe haemophilia A
receiving recombinant or plasma-derived factor VIII: a budget-impact analysis.
PMID- 28686157
TI - The role of recombinant activated factor VII in the haematological management of
elective orthopaedic surgery in haemophilia A patients with inhibitors.
AB - The clinical profile and expectations of haemophilic patients with inhibitors
have changed over the last three decades, mainly because of the prolongation of
life-expectancy, often resulting in an increase of the orthopaedic burden.
Recombinant activated factor VII (rFVIIa) is the most frequently used bypassing
agent in haemophilia patients with inhibitors during elective orthopaedic
surgery. For nearly 30 years, rFVIIa has been successfully used to control
haemostasis in several major and minor surgical procedures. Clinical trials, case
series, reports and surveys were progressively aimed at optimising rFVIIa usage
in very demanding conditions managed in highly specialised centres.
Recommendations from consensus opinions and guidelines have been provided on the
basis of this clinical experience.
PMID- 28686158
TI - Diagnosis and management of patients with von Willebrand's disease in Italy: an
Expert Meeting Report.
PMID- 28686159
TI - Deconstruction of the Ras switching cycle through saturation mutagenesis.
AB - Ras proteins are highly conserved signaling molecules that exhibit regulated,
nucleotide-dependent switching between active and inactive states. The high
conservation of Ras requires mechanistic explanation, especially given the
general mutational tolerance of proteins. Here, we use deep mutational scanning,
biochemical analysis and molecular simulations to understand constraints on Ras
sequence. Ras exhibits global sensitivity to mutation when regulated by a GTPase
activating protein and a nucleotide exchange factor. Removing the regulators
shifts the distribution of mutational effects to be largely neutral, and reveals
hotspots of activating mutations in residues that restrain Ras dynamics and
promote the inactive state. Evolutionary analysis, combined with structural and
mutational data, argue that Ras has co-evolved with its regulators in the
vertebrate lineage. Overall, our results show that sequence conservation in Ras
depends strongly on the biochemical network in which it operates, providing a
framework for understanding the origin of global selection pressures on proteins.
PMID- 28686160
TI - The cyanobacterial circadian clock follows midday in vivo and in vitro.
AB - Circadian rhythms are biological oscillations that schedule daily changes in
physiology. Outside the laboratory, circadian clocks do not generally free-run
but are driven by daily cues whose timing varies with the seasons. The principles
that determine how circadian clocks align to these external cycles are not well
understood. Here, we report experimental platforms for driving the cyanobacterial
circadian clock both in vivo and in vitro. We find that the phase of the
circadian rhythm follows a simple scaling law in light-dark cycles, tracking
midday across conditions with variable day length. The core biochemical
oscillator comprised of the Kai proteins behaves similarly when driven by
metabolic pulses in vitro, indicating that such dynamics are intrinsic to these
proteins. We develop a general mathematical framework based on instantaneous
transformation of the clock cycle by external cues, which successfully predicts
clock behavior under many cycling environments.
PMID- 28686161
TI - Theta oscillations locked to intended actions rhythmically modulate perception.
AB - Ongoing brain oscillations are known to influence perception, and to be reset by
exogenous stimulations. Voluntary action is also accompanied by prominent
rhythmic activity, and recent behavioral evidence suggests that this might be
coupled with perception. Here, we reveal the neurophysiological underpinnings of
this sensorimotor coupling in humans. We link the trial-by-trial dynamics of EEG
oscillatory activity during movement preparation to the corresponding dynamics in
perception, for two unrelated visual and motor tasks. The phase of theta
oscillations (~4 Hz) predicts perceptual performance, even >1 s before movement.
Moreover, theta oscillations are phase-locked to the onset of the movement.
Remarkably, the alignment of theta phase and its perceptual relevance unfold with
similar non-monotonic profiles, suggesting their relatedness. The present work
shows that perception and movement initiation are automatically synchronized
since the early stages of motor planning through neuronal oscillatory activity in
the theta range.
PMID- 28686162
TI - [The etiology of obsessive-compulsive disorder from the aspects of attachment
theory, with special regard to perceived parental treatment, attachment patterns
and emotion regulation difficulties].
AB - BACKGROUND AND AIMS: The focus of our study was the etiology of obsessive
compulsive disorder from attachment aspects. Our aim was to examine the
representations of perceived parental treatment, attachment patterns and the
level of emotion regulation of people who suffer from obsessive-compulsive
disorder. METHOD: 223 people participated in our study. The clinical group
consisted of 92 persons with obsessive-compulsive symptoms, while the control
group involved 131 people without OC symptoms. In the study we used the Young
Parenting Inventory, the Relationship Questionnaire, and the Difficulties in
Emotion Regulation Scale. Besides we compiled a questionnaire based on the DSM-5
and a demographic questionnaire. Respondents could fill the questionnaires
online. RESULTS: The clinical group is characterized by significantly higher
toxic frustration of each five basic emotional needs than the control group.
Specifically, in the case of people with OC smptoms the toxic parental treatments
for Defectiveness/ Shame, Dependence/Incompetence, Enmeshment/Undeveloped self,
Entitlement/Grandiosity, Approval-seeking/ Recognition-seeking,
Negativity/Pessimism, Emotional inhibition, Unrelenting
standards/Hypercriticalness and Punitiveness were significantly more frequent
than in the control group. The OC group is also characterized by significantly
lower rate of secure attachment style, while dismissive attachment style proved
to be the most frequent attachment style among them. The OC group also struggle
with significantly higher level of emotion regulation difficulties.
PMID- 28686163
TI - ["Better late than never". Studying procrastination among students].
AB - INTRODUCTION: The purpose of the study is to investigate dispositional
procrastination, procrastination types, and an operative measurement of this
behavior in academic environment. Procrastination is a common and problematic
phenomenon that explains the need for a comprehensive and complex approach of
this behavior. The main focus of the study was to investigate the incidence and
incidence of the different types of procrastination. Furthermore, we aimed to
test the correspondence between dispositional procrastination and the operative
measurement. METHODS: The sample consisted of 131 participants. Lay's
Procrastination Scale was used to measure dispositional procrastination and the
Types of procrastination questionnaire was applied to assess the frequency of its
different types. Furthermore an operative measurement was gained by assigning a
deadline for returning the paper and pensil form of the questionnaire.
Participants received a message informing them that the deadline had been
extended by three more days on the last night before the deadline. RESULTS: Based
on the empirical results 63% of the participants can be classified as
procrastinator. In regards of the different types of procrastination,
"perfectionist" and "crisis-maker" types were the most frequent. A positive
correlation was found between dispositional procrastination and the operative
measurement of procrastination. CONCLUSIONS: The results proved the common
presence of procrastination, as well as the close connection between its
dispositional and operative measure. Besides, they raise attention to the
perfectionist and crisis-maker types of procrastination.
PMID- 28686164
TI - [The role of cognitive emotional self-regulation in adolescence in levels of
depression, psychosomatic symptoms and subjective well-being].
AB - BACKGROUND AND AIMS OF THE STUDY: More and more studies suggest that mental
health may be determined by processes of emotional self-regulation. Emotion
regulation is a complex concept which can be explicit and implicit and includes
different cognitive and behavioral processes: evaluation, modifying of emotional
reaction to accomplish goals. Our research aim was to explore the use of
cognitive emotional self-regulation strategies related to mental health
indicators among adolescents. METHOD: The youth study was performed with a sample
size of 1245 participants in Mako, in 2016. Data collection was based on self
administrated questionnaries that contained items on mental health, subjective
well-being and background of sociodemographics. The data were compared on the
basis of gender differences and tested by multiple linear regression analysis to
map associations between the regulation strategies and mental health indicators:
depression, psychosomatic symptoms, satisfaction with life. RESULTS: Girls
reported higher levels of depression and psychosomatic symptoms and lower
satisfaction with life than boys. Significant differences were observed between
boys and girls in using rumination, positive refocusing, selfblame, others-blame
and putting into perspective regulation strategy. In addition the nonadaptive
strategies were proved to be related to higher depression and psychosomatic
symptom scores, whereas adaptive strategies to higher level of satisfaction with
life in both boys and girls. CONCLUSIONS: The study draws attention to the
importance of cognitive emotion regulation strategies from the point of view of
mental health and to explore the background factors of cognitive processes of
emotional self-regulation.
PMID- 28686165
TI - [The diagnosis and treatment of bipolar affective disorders].
AB - No abstcarct available.
PMID- 28686166
TI - [A Narrative Review on the Efficacy Studies of Social Skills Training for
Patients with Schizophrenia with Special Focus on the Relationship between Social
Cognition and Social Skills].
AB - No abstcarct available.
PMID- 28686167
TI - [Forensic aspects of sexul assault].
AB - No abstcarct available.
PMID- 28686168
TI - The analysis and assessment of the effect of selected endo- and exogenous
substances on prevention and treatment of selected conditions and injuries within
the musculoskeletal system.
AB - The aim of the presented report, prepared based on the results of the newest
studies available in the reference sources, is the analysis and assessment of the
important endo- and exogenous substances, whose role and significance in
prevention and complex treatment of civilization-related diseases (including the
pathological conditions and injuries of the musculoskeletal system) can be
essential and significantly contribute to the improvement of the efficacy of the
accepted treatment approach. Three substances, namely a-lipoic acid, y-linolenic
acid and a-linoleic acid were subject to a detailed analysis and assessment.
PMID- 28686169
TI - Review of pseudogaps in strongly interacting Fermi gases.
AB - A central challenge in modern condensed matter physics is developing the tools
for understanding nontrivial yet unordered states of matter. One important idea
to emerge in this context is that of a 'pseudogap': the fact that under
appropriate circumstances the normal state displays a suppression of the single
particle spectral density near the Fermi level, reminiscent of the gaps seen in
ordered states of matter. While these concepts arose in a solid state context,
they are now being explored in cold gases. This article reviews the current
experimental and theoretical understanding of the normal state of strongly
interacting Fermi gases, with particular focus on the phenomonology which is
traditionally associated with the pseudogap.
PMID- 28686170
TI - Role of alkali metal promoter in enhancing lateral growth of monolayer transition
metal dichalcogenides.
AB - Synthesis of monolayer transition metal dichalcogenides (TMDs) via chemical vapor
deposition relies on several factors such as precursor, promoter, substrate, and
surface treatment of substrate. Among them, the use of promoter is crucial for
obtaining uniform and large-area monolayer TMDs. Although promoters have been
speculated to enhance adhesion of precursors to the substrate, their precise role
in the growth mechanism has rarely been discussed. Here, we report the role of
alkali metal promoter in growing monolayer TMDs. The growth occurred via the
formation of sodium metal oxides which prevent the evaporation of metal
precursor. Furthermore, the silicon oxide substrate helped to decrease the Gibbs
free energy by forming sodium silicon oxide compounds. The resulting sodium metal
oxide was anchored within such concavities created by corrosion of silicon oxide.
Consequently, the wettability of the precursors to silicon oxide was improved,
leading to enhance lateral growth of monolayer TMDs.
PMID- 28686171
TI - Systematic investigation on the validity of partition model dosimetry for 90Y
radioembolization using Monte Carlo simulation.
AB - We aimed to investigate the validity of the partition model (PM) in estimating
the absorbed doses to liver tumour ([Formula: see text]), normal liver tissue
([Formula: see text]) and lungs ([Formula: see text]), when cross-fire
irradiations between these compartments are being considered. MIRD-5 phantom
incorporated with various treatment parameters, i.e. tumour involvement (TI),
tumour-to-normal liver uptake ratio (T/N) and lung shunting (LS), were simulated
using the Geant4 Monte Carlo (MC) toolkit. 108 track histories were generated for
each combination of the three parameters to obtain the absorbed dose per activity
uptake in each compartment ([Formula: see text], [Formula: see text], and
[Formula: see text]). The administered activities, A were estimated using PM, so
as to achieve either limiting doses to normal liver, [Formula: see text] or
lungs, [Formula: see text] (70 or 30 Gy, respectively). Using these administered
activities, the activity uptake in each compartment ([Formula: see text],
[Formula: see text], and [Formula: see text]) was estimated and multiplied with
the absorbed dose per activity uptake attained using the MC simulations, to
obtain the actual dose received by each compartment. PM overestimated [Formula:
see text] by 11.7% in all cases, due to the escaped particles from the lungs.
[Formula: see text] and [Formula: see text] by MC were largely affected by T/N,
which were not considered by PM due to cross-fire exclusion at the tumour-normal
liver boundary. These have resulted in the overestimation of [Formula: see text]
by up to 8% and underestimation of [Formula: see text] by as high as -78%, by
PM. When [Formula: see text] was estimated via PM, the MC simulations showed
significantly higher [Formula: see text] for cases with higher T/N, and LS ?
10%. All [Formula: see text] and [Formula: see text] by MC were overestimated by
PM, thus [Formula: see text] were never exceeded. PM leads to inaccurate dose
estimations due to the exclusion of cross-fire irradiation, i.e. between the
tumour and normal liver tissue. Caution should be taken for cases with higher TI
and T/N, and lower LS, as they contribute to major underestimation of [Formula:
see text]. For [Formula: see text], a different correction factor for dose
calculation may be used for improved accuracy.
PMID- 28686172
TI - Ultrasonic computed tomography based on full-waveform inversion for bone
quantitative imaging.
AB - We introduce an ultrasonic quantitative imaging method for long bones based on
full-waveform inversion. The cost function is defined as the difference in the L
2-norm sense between observed data and synthetic results at a given iteration of
the iterative inversion process. For simplicity, and in order to reduce the
computational cost, we use a two-dimensional acoustic approximation. The inverse
problem is solved iteratively based on a quasi-Newton technique called the
Limited-memory Broyden-Fletcher-Goldfarb-Shanno method. We show how the technique
can be made to work fine for benchmark models consisting of a single cylinder,
and then five cylinders, the latter case including significant multiple
diffraction effects. We then show pictures obtained for a tibia-fibula bone pair
model. Convergence is fast, typically in 15 to 30 iterations in practice in each
frequency band used. We discuss the so-called 'cycle skipping' effect that can
occur in such full waveform inversion techniques and make them remain trapped in
a local minimum of the cost function. We illustrate strategies that can be used
in practice to avoid this. Future work should include viscoelastic materials
rather than acoustic, and real data instead of synthetic data.
PMID- 28686173
TI - Comparison of fractional exhaled nitric oxide levels in chronic obstructive
pulmonary disease, bronchial asthma and healthy subjects of Nepal.
AB - INTRODUCTION: Fractional exhaled nitric oxide levels in exhaled breath can
indicate ongoing eosinophilic airway inflammation, specifically in asthma. But
its utility is being explored for central airway inflammations, including chronic
obstructive pulmonary disease. Normal levels of fractional exhaled nitric oxide
(FENO50) have been defined in different studies but not in Nepal. This study
compares FENO50 levels in normal subjects, asthma and chronic obstructive
pulmonary disease. METHODS: Single breath estimation of FENO50 was measured by a
handheld electrochemical sensor-based device in normal non-smoking adults (n =
106), clinically controlled asthma (n = 106) and stable chronic obstructive
pulmonary disease (n = 106). RESULTS: The geometric mean for FENO50 was 14 parts
per billion (ppb) with a median of 16 ppb, first quartile at 11 ppb and third
quartile at 20 ppb in normal non-smoking adults. The values were 31 ppb
(geometric mean), 34 ppb (median), 17 ppb (first quartile) and 79 ppb (third
quartile) in clinically controlled asthma. Similarly the values were 10 ppb
(geometric mean), 11 ppb (median), 6 ppb (first quartile) and 17 ppb (third
quartile) in stable chronic obstructive airway disease. The log-transformed data
showed significantly higher FENO50 levels in the asthma group compared with the
normal (p < 0.001) and chronic obstructive airway disease (p < 0.001). However,
levels were similar between healthy and chronic obstructive airway disease groups
(p = 0.08). CONCLUSIONS: FENO50 levels were higher in bronchial asthma (despite
disease control) than in normal non-smoking adults and subjects with stable
chronic obstructive pulmonary disease. Levels of FENO50 were similar between the
chronic obstructive airway disease and normal groups.
PMID- 28686174
TI - USEQ: A Short Questionnaire for Satisfaction Evaluation of Virtual Rehabilitation
Systems.
AB - New emerging technologies have proven their efficacy in aiding people in their
rehabilitation. The tests that are usually used to evaluate usability (in
general) or user satisfaction (in particular) of this technology are not
specifically focused on virtual rehabilitation and patients. The objective of
this contribution is to present and evaluate the USEQ (User Satisfaction
Evaluation Questionnaire). The USEQ is a questionnaire that is designed to
properly evaluate the satisfaction of the user (which constitutes part of
usability) in virtual rehabilitation systems. Forty patients with balance
disorders completed the USEQ after their first session with ABAR (Active Balance
Rehabilitation), which is a virtual rehabilitation system that is designed for
the rehabilitation of balance disorders. Internal consistency analysis and
exploratory factor analysis were carried out to identify the factor structure of
the USEQ. The six items of USEQ were significantly associated with each other,
and the Cronbach alpha coefficient for the questionnaire was 0.716. In an
analysis of the principal components, a one-factor solution was considered to be
appropriate. The findings of the study suggest that the USEQ is a reliable
questionnaire with adequate internal consistency. With regard to patient
perception, the patients found the USEQ to be an easy-to-understand questionnaire
with a convenient number of questions.
PMID- 28686175
TI - Ultrasensitive Magnetic Field Sensing Based on Refractive-Index-Matched Coupling.
AB - An ultrasensitive magnetic field sensor is proposed and investigated
experimentally. The no-core fiber is fusion-spliced between two pieces of single
mode fibers and then immersed in magnetic fluid with an appropriate value of
refractive index. Under the refractive-index-matched coupling condition, the
guided mode becomes leaky and a coupling wavelength dip in the transmission
spectrum of the structure is observed. The coupling wavelength dip is extremely
sensitive to the ambient environment. The excellent sensitivity to the refractive
index is measured to be 116.681 MUm/RIU (refractive index unit) in the refractive
index range of 1.45691-1.45926. For the as-fabricated sensors, the highest
magnetic field sensing sensitivities of 6.33 and 1.83 nm/mT are achieved at low
and high fields, respectively. The sensitivity is considerably enhanced compared
with those of previously designed, similar structures.
PMID- 28686176
TI - Routing in Mobile Wireless Sensor Networks: A Leader-Based Approach.
AB - This paper presents a leader-based approach to routing in Mobile Wireless Sensor
Networks (MWSN). Using local information from neighbour nodes, a leader election
mechanism maintains a spanning tree in order to provide the necessary adaptations
for efficient routing upon the connectivity changes resulting from the mobility
of sensors or sink nodes. We present two protocols following the leader election
approach, which have been implemented using Castalia and OMNeT++. The protocols
have been evaluated, besides other reference MWSN routing protocols, to analyse
the impact of network size and node velocity on performance, which has
demonstrated the validity of our approach.
PMID- 28686178
TI - Cultivating Fluorescent Flowers with Highly Luminescent Carbon Dots Fabricated by
a Double Passivation Method.
AB - In this work, we present the fabrication of highly luminescent carbon dots (CDs)
by a double passivation method with the assistance of Ca(OH)2. In the reaction
process, Ca2+ protects the active functional groups from overconsumption during
dehydration and carbonization, and the electron-withdrawing groups on the CD
surface are converted to electron-donating groups by the hydroxyl ions. As a
result, the fluorescence quantum yield of the CDs was found to increase with
increasing Ca(OH)2 content in the reaction process. A blue-shift optical spectrum
of the CDs was also found with increasing Ca(OH)2 content, which could be
attributed to the increasing of the energy gaps for the CDs. The highly
photoluminescent CDs obtained (quantum yield: 86%) were used to cultivate
fluorescent carnations by a water culture method, while the results of
fluorescence microscopy analysis indicated that the CDs had entered the plant
tissue structure.
PMID- 28686177
TI - The Telomeric Complex and Metabolic Disease.
AB - The attrition of telomeres is believed to be a key event not only in mammalian
aging, but also in disturbed nutrient sensing, which could lead to numerous
metabolic dysfunctions. The current debate focuses mainly on the question whether
telomere shortening, e.g., as a heritable trait, may act as a cause or rather
represents a consequence of such chronic diseases. This review discusses the
damaging events that ultimately may lead or contribute to telomere shortening and
can be associated with metabolic diseases.
PMID- 28686179
TI - When Less Is Good, Is None Better? The Prognostic and Therapeutic Significance of
Peri-Transplant Minimal Residual Disease Assessment in Pediatric Acute
Lymphoblastic Leukemia.
AB - The measurement of minimal residual disease (MRD) in pediatric acute
lymphoblastic leukemia (ALL) has become the most important prognostic tool of,
and the backbone to, upfront risk stratification. While MRD assessment is the
standard of care for assessing response and predicting outcomes for pediatric
patients with ALL receiving chemotherapy, its use in allogeneic hematopoietic
stem cell transplant (HSCT) has been less clearly defined. Herein, we discuss the
importance of MRD assessment during the peri-HSCT period and its role in
prognostication and management.
PMID- 28686180
TI - Assessing Probabilistic Risk Assessment Approaches for Insect Biological Control
Introductions.
AB - The introduction of biological control agents to new environments requires host
specificity tests to estimate potential non-target impacts of a prospective
agent. Currently, the approach is conservative, and is based on physiological
host ranges determined under captive rearing conditions, without consideration
for ecological factors that may influence realized host range. We use historical
data and current field data from introduced parasitoids that attack an endemic
Lepidoptera species in Hawaii to validate a probabilistic risk assessment (PRA)
procedure for non-target impacts. We use data on known host range and habitat use
in the place of origin of the parasitoids to determine whether contemporary
levels of non-target parasitism could have been predicted using PRA. Our results
show that reasonable predictions of potential non-target impacts may be made if
comprehensive data are available from places of origin of biological control
agents, but scant data produce poor predictions. Using apparent mortality data
rather than marginal attack rate estimates in PRA resulted in over-estimates of
predicted non-target impact. Incorporating ecological data into PRA models
improved the predictive power of the risk assessments.
PMID- 28686181
TI - How Can Synergism of Traditional Medicines Benefit from Network Pharmacology?
AB - Many prescriptions of traditional medicines (TMs), whose efficacy has been
tested in clinical practice, have great therapeutic value and represent an
excellent resource for drug discovery. Research into single compounds of TMs,
such as artemisinin from Artemisia annua L., has achieved great success; however,
it has become evident that a TM prescription (which frequently contains various
herbs or other components) has a synergistic effect in effecting a cure or
reducing toxicity. Network pharmacology targets biological networks and analyzes
the links among drugs, targets, and diseases in those networks. Comprehensive,
systematic research into network pharmacology is consistent with the perspective
of holisticity, which is a main characteristic of many TMs. By means of network
pharmacology, research has demonstrated that many a TM show a synergistic effect
by acting at different levels on multiple targets and pathways. This approach
effectively bridges the gap between modern medicine and TM, and it greatly
facilitates studies into the synergistic actions of TMs. There are different
kinds of synergistic effects with TMs, such as synergy among herbs, effective
parts, and pure compounds; however, for various reasons, new drug discovery
should at present focus on synergy among pure compounds.
PMID- 28686182
TI - A Purified Serine Protease from Nereis virens and Its Impaction of Apoptosis on
Human Lung Cancer Cells.
AB - Nereis active protease (NAP) is a novel fibrinolytic active serine protease from
the polychaete Nereis virens. In this study, NAP was purified from Nereis virens
and the effects of NAP on human lung cancer cells were investigated. Our results
indicated that NAP inhibited the proliferation and induced apoptosis of H1299
cells in a time- and dose-dependent manner. The loss of mitochondrial membrane
potential, the activation of Bax and cleaved-caspase 3/9, the release of
cytochrome C, and the suppression of Bcl-2 and poly-ADP ribose polymerase were
observed in NAP-treated H1299 cells by flow cytometry and Western blotting.
Moreover, the expression levels of Bax and Bcl-2 mRNA were determined by real
time quantitative polymerase chain reaction and the Bax/Bcl-2 expression ratio
was increased in the NAP-treated cell lines. The results indicated that NAP
induced apoptosis may be related to mitochondria mediated apoptosis and occurs
through caspase-dependent pathways. Then, the effects of NAP on tumor growth in
animal models were observed, where 5 or 10 mg/kg of NAP noticeably reduced tumor
volume and weight and increased apoptosis as determined by Western blotting when
compared to the negative control group. Therefore, our findings suggest that NAP
could be a hopeful anticancer medicine for its propensity to inhibit growth and
induce of apoptosis in human lung cancer cells.
PMID- 28686183
TI - Development and Evaluation of a Novel Set of EST-SSR Markers Based on
Transcriptome Sequences of Black Locust (Robinia pseudoacacia L.).
AB - Black locust (Robinia pseudoacacia L. of the family Fabaceae) is an ecologically
and economically important deciduous tree. However, few genomic resources are
available for this forest species, and few effective expressed sequence tag
derived simple sequence repeat (EST-SSR) markers have been developed to date. In
this study, paired-end sequencing was used to sequence transcriptomes of R.
pseudoacacia by the Illumina HiSeq TM2000 platform, and EST-SSR loci were
identified by de novo assembly. Furthermore, a total of 1697 primer pairs were
successfully designed, from which 286 primers met the selection screening
criteria; 94 pairs were randomly selected and tested for validation using
polymerase chain reaction amplification. Forty-five primers were verified as
polymorphic, with clear bands. The polymorphism information content values were
0.033-0.765, the number of alleles per locus ranged from 2 to 10, and the
observed and expected heterozygosities were 0.000-0.931 and 0.035-0.810,
respectively, indicating a high level of informativeness. Subsequently, 45
polymorphic EST-SSR loci were tested for amplification efficiency, using the
verified primers, in an additional nine species of Leguminosae, 23 loci were
amplified in more than three species, of which two loci were amplified
successfully in all species. These EST-SSR markers provide a valuable tool for
investigating the genetic diversity and population structure of R. pseudoacacia,
constructing a DNA fingerprint database, performing quantitative trait locus
mapping, and preserving genetic information.
PMID- 28686184
TI - Place of Birth and Sleep Duration: Analysis of the National Health Interview
Survey (NHIS).
AB - While sleep disturbance has been related to a number of negative health outcomes,
few studies have examined the relationship between place of birth and sleep
duration among individuals living in the US. Data for 416,152 adult participants
in the 2000-2013 National Health Interview Survey (NHIS), who provided self
reported hours of sleep and place of birth were examined. Associations were
explored between healthy sleep (7-8 h), referenced to unhealthy sleep (<7 or >8
h), and place of birth using multivariate logistic regression analysis. The mean
age of the sample was 47.4 +/- 0.03 years; 56% were female. Of the respondents,
61.5% reported experiencing healthy sleep, 81.5% reported being born in the US
and 18.5% were foreign-born adults. Descriptive statistics revealed that Indian
Subcontinent-born respondents (71.7%) were more likely to report healthy sleep
compared to US-born respondents (OR = 1.53, 95% CI = 1.37-1.71, p < 0.001),
whereas African-born respondents (43.5%) were least likely to report healthy
sleep (OR = 0.78, 95% CI = 0.70-0.87, p < 0.001). These findings suggest that
place of birth should be considered in the assessment of risk factors for
unhealthy sleep.
PMID- 28686185
TI - The Roles of beta-Integrin of Chinese Shrimp (Fenneropenaeus chinensis) in WSSV
Infection.
AB - Our previous study demonstrated that an integrin beta subunit of Chinese shrimp
(Fenneropenaeus chinensis) (FcbetaInt) plays an important role in white spot
syndrome virus (WSSV) infection. In the present work, in order to further
elucidate the potential role of FcbetaInt in WSSV infection, the recombinant
extracellular domain of beta integringene of F. Chinensis (rFcbetaInt-ER) was
expressed in Escherichia coli BL21 (DE3), and the eukaryotic expression plasmid
PcDNA3.1-FcbetaInt-ER (PFcbetaInt-ER) was also constructed. Far-western blotting
was performed to determine the binding specificity of rFcbetaInt-ER to WSSV
envelope proteins, and results showed that rFcbetaInt-ER was able to specifically
interact with rVP31, rVP37, rVP110 and rVP187. Moreover, the blocking effects of
mouse anti-rFcbetaint-ER antibodies were both detected in vivo and in vitro. The
ELISA and Dot-blotting in vitro assays both showed that mouse anti-rFcbetaInt-ER
antibodies could partially block the binding of WSSV to the hemocyte membrane of
F. chinensis. In the in vivo assays, the mortality of shrimp injected with WSSV
mixed with anti-rFcbetaInt-ER antibodies was delayed, and was lower than in the
control group. While the shrimp were intramuscularly injected with PFcbetaInt-ER,
transcripts of PFcbetaInt-ER could be detected in different shrimp tissues within
7 days, and the mortality of shrimp injected with PFcbetaInt-ER was also delayed
and lower compared with the control group post WSSV challenge. Furthermore, gene
silencing technology was also used to verify the effect of FcbetaInt in WSSV
infection, and results showed that the expression levels of the WSSV immediate
early gene iel, early gene wsv477, and late gene VP28 and the mortality of F.
Chinensis were all significantly decreased in the FcbetaInt knock-down hemocyctes
compared to the control group. Taken together, these results suggest that
FcbetaInt plays important roles in WSSV infection.
PMID- 28686186
TI - Development of a New Microextraction Fiber Combined to On-Line Sample Stacking
Capillary Electrophoresis UV Detection for Acidic Drugs Determination in Real
Water Samples.
AB - A new analytical method coupling a (off-line) solid-phase microextraction with an
on-line capillary electrophoresis (CE) sample enrichment technique was developed
for the analysis of ketoprofen, naproxen and clofibric acid from water samples,
which are known as contaminants of emerging concern in aquatic environments. New
solid-phase microextraction fibers based on physical coupling of chromatographic
supports onto epoxy glue coated needle were studied for the off-line
preconcentration of these micropollutants. Identification and quantification of
such acidic drugs were done by capillary zone electrophoresis (CZE) using
ultraviolet diode array detection (DAD). Further enhancement of concentration
sensitivity detection was achieved by on-line CE "acetonitrile stacking"
preconcentration technique. Among the eight chromatographic supports
investigated, Porapak Q sorbent showed higher extraction and preconcentration
capacities. The screening of parameters that influence the microextraction
process was carried out using a two-level fractional factorial. Optimization of
the most relevant parameters was then done through a surface response three
factor Box-Behnken design. The limits of detection and limits of quantification
for the three drugs ranged between 0.96 and 1.27 ug?L-1 and 2.91 and 3.86 ug?L-1,
respectively. Recovery yields of approximately 95 to 104% were measured. The
developed method is simple, precise, accurate, and allows quantification of
residues of these micropollutants in Genil River water samples using inexpensive
fibers.
PMID- 28686187
TI - Cuticular Waxes of Arabidopsis thaliana Shoots: Cell-Type-Specific Composition
and Biosynthesis.
AB - It is generally assumed that all plant epidermis cells are covered with cuticles,
and the distinct surface geometries of pavement cells, guard cells, and trichomes
imply functional differences and possibly different wax compositions. However,
experiments probing cell-type-specific wax compositions and biosynthesis have
been lacking until recently. This review summarizes new evidence showing that
Arabidopsis trichomes have fewer wax compound classes than pavement cells, and
higher amounts of especially long-chain hydrocarbons. The biosynthesis machinery
generating this characteristic surface coating is discussed. Interestingly, wax
compounds with similar, long hydrocarbon chains had been identified previously in
some unrelated species, not all of them bearing trichomes.
PMID- 28686188
TI - Dietary Choline and Betaine and Risk of CVD: A Systematic Review and Meta
Analysis of Prospective Studies.
AB - Studies implicate choline and betaine metabolite trimethylamine N-oxide (TMAO) in
cardiovascular disease (CVD). We conducted a systematic review and random-effects
meta-analysis to quantify a summary estimated effect of dietary choline and
betaine on hard CVD outcomes (incidence and mortality). Eligible studies were
prospective studies in adults with comprehensive diet assessment and follow-up
for hard CVD endpoints. We identified six studies that met our criteria,
comprising 18,076 incident CVD events, 5343 CVD deaths, and 184,010 total
participants. In random effects meta-analysis, incident CVD was not associated
with choline (relative risk (RR): 1.00; 95% CI: 0.98, 1.02) or betaine (RR: 0.99;
95% CI: 0.98, 1.01) intake. Results did not vary by study outcome (incident
coronary heart disease, stroke, total CVD) and there was no evidence for
heterogeneity among studies. Only two studies provided data on
phosphatidylcholine and CVD mortality. Random effects meta-analysis did not
support an association between choline and CVD mortality (RR: 1.09, 95% CI: 0.89,
1.35), but one study supported a positive association and there was significant
heterogeneity (I2 = 84%, p-value < 0.001). Our findings do not support an
association between dietary choline/betaine with incident CVD, but call for
further research into choline and CVD mortality.
PMID- 28686189
TI - Correction: Jang, S.-E.; et al. Lactobacillus rhamnosus HN001 and Lactobacillus
acidophilus La-14 Attenuate Gardnerella vaginalis-Infected Bacterial Vaginosis in
Mice. Nutrients 2017, 9, 531.
AB - We would like to submit the following corrections to our recently published paper
[1] due to the reported wrong name of probiotic mixture and the dose of some
drugs. ...].
PMID- 28686190
TI - Non-Noble Metal Oxide Catalysts for Methane Catalytic Combustion: Sonochemical
Synthesis and Characterisation.
AB - The aim of this study was to obtain nanocrystalline mixed metal-oxide-ZrO2
catalysts via a sonochemically-induced preparation method. The effect of a
stabiliser's addition on the catalyst parameters was investigated by several
characterisation methods including X-ray Diffraction (XRD), nitrogen adsorption,
X-ray fluorescence (XRF), scanning electron microscopy (SEM) equipped with energy
dispersive X-ray spectrometer (EDS), transmission electron microscopy (TEM) and
uRaman. The sonochemical preparation method allowed us to manufacture the
catalysts with uniformly dispersed metal-oxide nanoparticles at the support
surface. The catalytic activity was tested in a methane combustion reaction. The
activity of the catalysts prepared by the sonochemical method was higher than
that of the reference catalysts prepared by the incipient wetness method without
ultrasonic irradiation. The cobalt and chromium mixed zirconia catalysts revealed
their high activities, which are comparable with those presented in the
literature.
PMID- 28686191
TI - The Gene-Lifestyle Interaction on Leptin Sensitivity and Lipid Metabolism in
Adults: A Population Based Study.
AB - BACKGROUND: Obesity has been associated with leptin resistance and this might be
caused by genetic factors. The aim of this study was to investigate the gene
lifestyle interaction between -866G/A UCP2 (uncoupling protein 2) gene
polymorphism, dietary intake and leptin in a population based study. METHODS:
This is a cross sectional study conducted in adults living at urban area of
Yogyakarta, Indonesia. Data of adiposity, lifestyle, triglyceride, high density
lipoprotein (HDL) cholesterol, leptin and UCP2 gene polymorphism were obtained in
380 men and female adults. RESULTS: UCP2 gene polymorphism was not significantly
associated with adiposity, leptin, triglyceride, HDL cholesterol, dietary intake
and physical activity (all p > 0.05). Leptin was lower in overweight subjects
with AA + GA genotypes than those with GG genotype counterparts (p = 0.029). In
subjects with AA + GA genotypes there was a negative correlation between leptin
concentration (r = -0.324; p < 0.0001) and total energy intake and this
correlation was not seen in GG genotype (r = -0.111; p = 0.188). CONCLUSIONS: In
summary, we showed how genetic variation in -866G/A UCP2 affected individual
response to leptin production. AA + GA genotype had a better leptin sensitivity
shown by its response in dietary intake and body mass index (BMI) and this
explained the protective effect of A allele to obesity.
PMID- 28686192
TI - [3+2] Cycloaddition of Tosylmethyl Isocyanide with Styrylisoxazoles: Facile
Access to Polysubstituted 3-(Isoxazol-5-yl)pyrroles.
AB - A facile access to polysubstituted 3-(isoxazol-5-yl)pyrroles was developed
through [3+2] cycloaddition of tosylmethyl isocyanide (TosMIC) and
styrylisoxazoles. In the presence of KOH, various styrylisoxazoles reacted
smoothly with tosylmethyl isocyanide and analogs to deliver a wide range of 3
(isoxazol-5-yl)pyrroles at ambient temperature. This transformation is
operationally simple, high-yielding, and displays broad substrate scope.
PMID- 28686193
TI - Reply to Alizadeh's Letter to the Editor Re: Lu, P.Y. et al., Nutrients 2017, 9,
38.
AB - n/a.
PMID- 28686194
TI - Orthodontic Metallic Lingual Brackets: The Dark Side of the Moon of Bond
Failures?
AB - Lingual orthodontics, among both young and adult patients, increased in
popularity during last years. The purposes of the present investigation were to
evaluate the shear bond strength (SBS) values and Adhesive Remnant Index (ARI)
scores of different lingual brackets compared with a vestibular control bracket.
One hundred bovine teeth were extracted and embedded in resin blocks. Four
different lingual brackets (Idea, Leone; STB, Ormco; TTR, RMO; 2D, Forestadent)
and a vestibular control bracket (Victory, 3M) were bonded to the bovine enamel
surfaces and subsequently shear tested to failure utilizing a Universal Testing
Machine. SBS values were measured. A microscopic evaluation was performed to
obtain ARI scores. Statistical analysis was performed at a statistically
significant level of p < 0.05 to determine significant differences in SBS values
and ARI Scores. No statistically significant variations in SBS were reported
among the different groups. Conversely, significant differences were shown in ARI
scores among the various groups. Clinical relevance of the present study is that
orthodontists can expect similar resistance to debonding forces from lingual
appliances as with vestibular brackets.
PMID- 28686195
TI - Assays to Monitor Autophagy Progression in Cell Cultures.
AB - The vast number of implications of autophagy in multiple areas of life sciences
and medicine has attracted the interest of numerous scientists that aim to unveil
the role of this process in specific physiological and pathological contexts.
Cell cultures are one of the most frequently used experimental setup for the
investigation of autophagy. As a result, it is essential to assess this highly
regulated molecular pathway with efficient and reliable methods. Each method has
its own advantages and disadvantages. Here, we present a review summarizing the
most established assays used to monitor autophagy induction and progression in
cell cultures, in order to guide researchers in the selection of the most optimal
solution for their experimental setup and design.
PMID- 28686197
TI - Vulnerability Reduction Needed to Maintain Current Burdens of Heat-Related
Mortality in a Changing Climate-Magnitude and Determinants.
AB - The health burden from heatwaves is expected to increase with rising global mean
temperatures and more extreme heat events over the coming decades. Health-related
effects from extreme heat are more common in elderly populations. The population
of Europe is rapidly aging, which will increase the health effects of future
temperatures. In this study, we estimate the magnitude of adaptation needed to
lower vulnerability to heat in order to prevent an increase in heat-related
deaths in the 2050s; this is the Adaptive Risk Reduction (ARR) needed.
Temperature projections under Representative Concentration Pathway (RCP) 4.5 and
RCP 8.5 from 18 climate models were coupled with gridded population data and
exposure-response relationships from a European multi-city study on heat-related
mortality. In the 2050s, the ARR for the general population is 53.5%, based on
temperature projections under RCP 4.5. For the population above 65 years in
Southern Europe, the ARR is projected to be 45.9% in a future with an unchanged
climate and 74.7% with climate change under RCP 4.5. The ARRs were higher under
RCP 8.5. Whichever emission scenario is followed or population projection
assumed, Europe will need to adapt to a great degree to maintain heat-related
mortality at present levels, which are themselves unacceptably high, posing an
even greater challenge.
PMID- 28686198
TI - Towards a Cognitive Radar: Canada's Third-Generation High Frequency Surface Wave
Radar (HFSWR) for Surveillance of the 200 Nautical Mile Exclusive Economic Zone.
AB - Canada's third-generation HFSWR forms the foundation of a maritime domain
awareness system that provides enforcement agencies with real-time persistent
surveillance out to and beyond the 200 nautical mile exclusive economic zone
(EEZ). Cognitive sense-and-adapt technology and dynamic spectrum management
ensures robust and resilient operation in the highly congested High Frequency
(HF) band. Dynamic spectrum access enables the system to simultaneously operate
on two frequencies on a non-interference and non-protected basis, without
impacting other spectrum users. Sense-and-adapt technologies ensure that the
system instantaneously switches to a new vacant channel on the detection of
another user or unwanted jamming signal. Adaptive signal processing techniques
mitigate against electrical noise, interference and clutter. Sense-and-adapt
techniques applied at the detector and tracker stages maximize the probability of
track initiation whilst minimizing the probability of false or otherwise
erroneous track data.
PMID- 28686196
TI - Protective Role for Antioxidants in Acute Kidney Disease.
AB - Acute kidney injury causes significant morbidity and mortality in the community
and clinic. Various pathologies, including renal and cardiovascular disease,
traumatic injury/rhabdomyolysis, sepsis, and nephrotoxicity, that cause acute
kidney injury (AKI), induce general or regional decreases in renal blood flow.
The ensuing renal hypoxia and ischemia promotes the formation of reactive oxygen
species (ROS) such as superoxide radical anions, peroxides, and hydroxyl
radicals, that can oxidatively damage biomolecules and membranes, and affect
organelle function and induce renal tubule cell injury, inflammation, and
vascular dysfunction. Acute kidney injury is associated with increased oxidative
damage, and various endogenous and synthetic antioxidants that mitigate source
and derived oxidants are beneficial in cell-based and animal studies. However,
the benefit of synthetic antioxidant supplementation in human acute kidney injury
and renal disease remains to be realized. The endogenous low-molecular weight,
non-proteinaceous antioxidant, ascorbate (vitamin C), is a promising therapeutic
in human renal injury in critical illness and nephrotoxicity. Ascorbate may exert
significant protection by reducing reactive oxygen species and renal oxidative
damage via its antioxidant activity, and/or by its non-antioxidant functions in
maintaining hydroxylase and monooxygenase enzymes, and endothelium and vascular
function. Ascorbate supplementation may be particularly important in renal injury
patients with low vitamin C status.
PMID- 28686199
TI - Postprandial Effects of Breakfast Glycemic Index on Vascular Function among Young
Healthy Adults: A Crossover Clinical Trial.
AB - This study aimed to evaluate the postprandial effects of high and low glycemic
index (GI) breakfasts on vascular function. It was a crossover trial that
included 40 young healthy adults (50% women), aged 20-40 years, who were
recruited at primary care settings. They consumed three experimental breakfasts
in randomized order, each one separated by a 1-week washout period: (1) control
conditions (only water); (2) low GI (LGI) breakfast (29.4 GI and 1489 KJ energy);
and (3) high GI (HGI) breakfast (64.0 GI and 1318 KJ energy). Blood samples were
collected at 60 and 120 min after each breakfast to determine glucose and insulin
levels. Vascular parameters were measured at 15 min intervals. Augmentation index
(AIx) was studied as a primary outcome. Secondary outcomes comprised glucose,
insulin, heart rate (HR) and pulse pressures (PPs). We found a trend toward
increased AIx, HR and PPs for the HGI versus the LGI breakfast. A significant
interaction between the type of breakfast consumed and all measured parameters
was identified (p < 0.05) except for central PP. Stratifying data by sex, this
interaction remained significant for AIx and augmentation pressure only in males
(p < 0.05). In conclusion, breakfast GI could affect postprandial vascular
responses in young healthy adults.
PMID- 28686200
TI - Cytotoxic Compounds from Aloe megalacantha.
AB - Phytochemical investigation of the ethyl acetate extract of the roots of Aloe
megalacantha led to the isolation of four new natural products-1,8
dimethoxynepodinol (1), aloesaponarin III (2), 10-O-methylchrysalodin (3) and
methyl-26-O-feruloyl-oxyhexacosanate (4)-along with ten known compounds. All
purified metabolites were characterized by NMR, mass spectrometric analyses and
comparison with literature data. The isolates were evaluated for their cytotoxic
activity against a human cervix carcinoma cell line KB-3-1 and some of them
exhibited good activity, with aloesaponarin II (IC50 = 0.98 uM) being the most
active compound.
PMID- 28686201
TI - Feeding a Mixture of Choline Forms during Lactation Improves Offspring Growth and
Maternal Lymphocyte Response to Ex Vivo Immune Challenges.
AB - Study objectives were to examine the impact of feeding a mixture of choline
forms, or a diet high in glycerophosphocholine (GPC) on maternal immune function
and offspring growth during lactation. Lactating Sprague-Dawley rat dams (n =
6/diet) were randomized to one of three diets, providing 1 g/kg total choline:
Control (100% free choline (FC)), Mixed Choline (MC; 50% phosphatidylcholine
(PC), 25% FC, 25% GPC), or High GPC (HGPC; 75% GPC, 12.5% PC, 12.5% FC). At 3
weeks, cell phenotypes and cytokine production with Concanavalin A (ConA)-or
lipopolysaccharide (LPS)-stimulated splenocytes and mesenteric lymphocytes were
measured. Feeding MC or HGPC diets improved pups' growth compared to Control
(+22% body weight, p < 0.05). In spleen, MC-and HGPC-fed dams had higher
proportions of cytotoxic (CD8+) T cells expressing CD27, CD71 and CD127, total B
cells (CD45RA+) and dendritic cells (OX6+OX62+), and produced less IL-6 and IFN
gamma after ConA than Control-fed dams (p < 0.05). MC and HGPC LPS-stimulated
splenocytes produced less IL-1beta and IL-6 than Control. ConA-stimulated
mesenteric lymphocytes from MC and HGPC dams produced more IL-2 and IFN-gamma
than Control (p < 0.05). In summary, feeding a mixture of choline forms during
lactation improved offspring growth and resulted in a more efficient maternal
immune response following mitogenic immune challenge.
PMID- 28686202
TI - Coinage Metal Complexes of the Carbenic Tautomer of a Conjugated Mesomeric
Betaine Akin to Nitron.
AB - This study was motivated by our recent observation that the analytical reagent
Nitron (2) is an "instant carbene", whose reaction with coinage metal salts MX
afforded complexes of its carbenic tautomer 1,4-diphenyl-3-phenylamino-1,2,4
triazol-5-ylidene (2'). Our aim was to establish an alkyl homologue of 2 in order
to achieve a carbenic tautomer of higher donicity. For this purpose 1-tert-butyl
4-methyl-1,2,4-triazol-4-ium-3-tert-butylaminide (6) was synthesized. Its
reactions with MX afforded complexes of the carbenic tautomer 1-tert-butyl-3-tert
butylamino-4-methyl-1,2,4-triazol-5-ylidene (6'). With a stoichiometric ratio of
1:1 complexes of the type [MX(6')] were obtained. A ratio of 2:1 furnished
complexes of the type [MX(6')2] or [M(6')2]X. 6' is a better sigma-donor and less
electrophilic than 2' according to NMR spectroscopic data of 6H[BF4] and 6' = Se,
respectively, and IR spectroscopic data of [RhCl(6')(CO)2] confirm that its net
electron donor capacity is superior to that of 2'. A comparison of the complexes
of 2' and 6' reveals two pronounced structural differences. [CuX(6')2] (X = Cl,
Br) exhibit more acute C-Cu-C bond angles than [CuX(2')2]. In contrast to
[CuCl(2')], [CuCl(6')] aggregates through Cu...Cu contacts of ca. 2.87 A,
compatible with cuprophilic interactions. These differences may be explained by
the complementary steric requirements of the t-Bu and the Me substituent of 6'.
PMID- 28686203
TI - Selective Dielectric Metasurfaces Based on Directional Conditions of Silicon
Nanopillars.
AB - Dielectric metasurfaces based on high refractive index materials have been
proposed recently. This type of structure has several advantages over their
metallic counterparts. In this work, we demonstrate that dielectric metasurfaces
can be theoretically designed satisfying Kerker's zero-forward condition. This is
the first time that a dielectric metasurface based on this principle has been
designed. A selective dielectric metasurface of silicon nanopillars is designed
to work at 632.8 nm. This structure could work both as a dielectric mirror and a
reject band filter. Furthermore, by scaling up the structure, it could be
possible to manufacture a terahertz (THz) dielectric mirror.
PMID- 28686204
TI - Metabolic and Blood Pressure Effects of Walnut Supplementation in a Mouse Model
of the Metabolic Syndrome.
AB - There is extensive evidence that walnut consumption is protective against
cardiovascular disease and diabetes in the healthy population, but the beneficial
effects of walnut consumption in individuals with the metabolic syndrome (MetS)
remain uncertain. We compared a range of cardio-metabolic traits and related
tissue gene expression associated with 21 weeks of dietary walnut supplementation
in a mouse model of MetS (MetS-Tg) and wild-type (WT) mice (n = 10 per genotype
per diet, equal males and females). Compared to standard diet, walnuts did not
significantly alter food consumption or body weight trajectory of either MetS-Tg
or WT mice. In MetS-Tg mice, walnuts were associated with reductions in oral
glucose area under the curve (gAUC, standard diet 1455 +/- 54, walnut 1146 +/-
91, p = 0.006) and mean arterial blood pressure (MAP, standard diet 100.6 +/-
1.9, walnut 73.2 +/- 1.8 mmHg, p < 0.001), with neutral effects on gAUC and MAP
in WT mice. However, in MetS-Tg mice, walnuts were also associated with trends
for higher plasma cholesterol (standard diet 4.73 +/- 0.18, walnut 7.03 +/- 1.99
mmol/L, p = 0.140) and triglyceride levels (standard diet 2.4 +/- 0.5, walnut 5.4
+/- 1.6 mmol/L, p = 0.061), despite lowering cholesterol and having no effect on
triglycerides in WT mice. Moreover, in both MetS-Tg and WT mice, walnuts were
associated with significantly increased liver expression of genes associated with
metabolism (Fabp1, Insr), cell stress (Atf6, Ddit3, Eif2ak3), fibrosis (Hgf, Sp1,
Timp1) and inflammation (Tnf, Ptpn22, Pparg). In conclusion, dietary walnuts were
associated with modest favourable effects in WT mice, but a combination of
beneficial and adverse effects in MetS-Tg mice, and up-regulation of hepatic pro
fibrotic and pro-inflammatory genes in both mouse strains.
PMID- 28686205
TI - Trifluoroethoxy-Coated Phthalocyanine Catalyzes Perfluoroalkylation of Alkenes
under Visible-Light Irradiation.
AB - We disclose herein the perfluoroalkylation of alkenes catalyzed by
trifluoroethoxy-coated zinc phthalocyanine under irradiation of visible light.
Perfluoroalkyl iodides were nicely incorporated into unsaturated substrates,
including alkyne, to provide perfluoroalkyl and iodide adducts in moderate to
good yields. Trifluoromethylation is also possible by trifluoromethyl iodide
under the same reaction conditions. The mechanistic study is discussed.
PMID- 28686206
TI - Novel N-Arylaminophosphonates Bearing a Pyrrole Moiety and Their Ecotoxicological
Properties.
AB - A wide range of biological activities of aminophosphonates predisposes them to
find applications as anticancer, antiviral, antimicrobial, antifungal, or
herbicidal agents. Despite a number of positive aspects of the use of
aminophosphonates, their applications may cause a risk to the environment, which
is well exemplified by the case of glyphosate. Therefore, scientists see a
pressing need to rate ecotoxicity of aminophosphonates. Nowadays, it is
recommended to use comprehensive tools to carry out appropriate and effective
risk assessments of toxic substances. For these purposes, tests based on the
acute toxicity of the luminescent bacteria Aliivibrio fischeri, as well as the
measurement of sub-chronic toxicity of the crustacean Heterocypris incongruens
seem to be the most convenient. A series of five diphenyl N-arylamino(pyrrole-2
yl)methylphosphonates was synthesized and preliminary evaluation of their
ecotoxicological properties was performed. In order to carry out such
investigations, we applied the two biotests mentioned above. Results showed that
the N-(4-nitrophenyl) derivative was the most toxic for bacteria in comparison to
other tested compounds. As for crustaceans, N-phenyl and N-naphthyl derivatives
were found to be the most harmful, simultaneously being relatively harmless for
bacteria. Such a phenomenon are discussed in correlation with the literature,
while its reason is discussed with respect to the aspect of structure of the
tested compounds.
PMID- 28686207
TI - Transgenic Strategies for Sparse but Strong Expression of Genetically Encoded
Voltage and Calcium Indicators.
AB - Rapidly progressing development of optogenetic tools, particularly genetically
encoded optical indicators, enables monitoring activities of neuronal circuits of
identified cell populations in longitudinal in vivo studies. Recently developed
advanced transgenic approaches achieve high levels of indicator expression.
However, targeting non-sparse cell populations leads to dense expression patterns
such that optical signals from neuronal processes cannot be allocated to
individual neurons. This issue is particularly pertinent for the use of
genetically encoded voltage indicators whose membrane-delimited signals arise
largely from the neuropil where dendritic and axonal membranes of many cells
intermingle. Here we address this need for sparse but strong expression of
genetically encoded optical indicators using a titratable recombination-activated
transgene transcription to achieve a Golgi staining-type indicator expression
pattern in vivo. Using different transgenic strategies, we also illustrate that
co-expression of genetically encoded voltage and calcium indicators can be
achieved in vivo for studying neuronal circuit input-output relationships.
PMID- 28686208
TI - Structural Elements Recognized by Abacavir-Induced T Cells.
AB - Adverse drug reactions are one of the leading causes of morbidity and mortality
in health care worldwide. Human leukocyte antigen (HLA) alleles have been
strongly associated with drug hypersensitivities, and the causative drugs have
been shown to stimulate specific T cells at the sites of autoimmune destruction.
The structural elements recognized by drug-specific T cell receptors (TCRs) in
vivo are poorly defined. Drug-stimulated T cells express TCRs specific for
peptide/HLA complexes, but the characteristics of peptides (sequence, or
endogenous or exogenous origin) presented in the context of small molecule drugs
are not well studied. Using HLA-B*57:01 mediated hypersensitivity to abacavir as
a model system, this study examines structural similarities of HLA presented
peptides recognized by drug-specific TCRs. Using the crystal structure of HLA
B*57:01 complexed with abacavir and an immunogenic self peptide, VTTDIQVKV SPT5a
976-984, peptide side chains exhibiting flexibility and solvent exposure were
identified as potential drug-specific T cell recognition motifs. Viral sequences
with structural motifs similar to the immunogenic self peptide were identified.
Abacavir-specific T cell clones were used to determine if virus peptides
presented in the context of abacavir stimulate T cell responsiveness. An abacavir
specific T cell clone was stimulated by VTQQAQVRL, corresponding to HSV1/2 230
238, in the context of HLA-B*57:01. These data suggest the T cell polyclonal
response to abacavir consists of multiple subsets, including T cells that
recognize self peptide/HLA-B*57:01 complexes and crossreact with viral
peptide/HLA-B*57:01 complexes due to similarity in TCR contact residues.
PMID- 28686209
TI - Detailed Characterization of Sympathetic Chain Ganglia (SChG) Neurons Supplying
the Skin of the Porcine Hindlimb.
AB - It is generally known that in the skin sympathetic fibers innervate various
dermal structures, including sweat glands, blood vessels, arrectores pilorum
muscles and hair follicles. However, there is a lack of data about the
distribution and chemical phenotyping of the sympathetic chain ganglia (SChG)
neurons projecting to the skin of the pig, a model that is physiologically and
anatomically very representative for humans. Thus, the present study was designed
to establish the origin of the sympathetic fibers supplying the porcine skin of
the hind leg, and the pattern(s) of putative co-incidence of dopamine-beta
hydroxylase (DbetaH) with pituitary adenylate cyclase-activating polypeptide
(PACAP), somatostatin (SOM), neuronal nitric oxide synthase, substance P,
vasoactive intestinal peptide, neuropeptide Y (NPY), leu5-enkephalin and galanin
(GAL) using combined retrograde tracing and double-labeling immunohistochemistry.
The Fast Blue-positive neurons were found in the L2-S2 ganglia. Most of them were
small-sized and contained DbetaH with PACAP, SOM, NPY or GAL. The findings of the
present study provide a detailed description of the distribution and chemical
coding of the SChG neurons projecting to the skin of the porcine hind leg. Such
data may be the basis for further studies concerning the plasticity of these
ganglia under experimental or pathological conditions.
PMID- 28686210
TI - Effects of Titanium Mesh Surfaces-Coated with Hydroxyapatite/beta-Tricalcium
Phosphate Nanotubes on Acetabular Bone Defects in Rabbits.
AB - The management of severe acetabular bone defects in revision reconstructive
orthopedic surgery is challenging. In this study, cyclic precalcification (CP)
treatment was used on both nanotube-surface Ti-mesh and a bone graft substitute
for the acetabular defect model, and its effects were assessed in vitro and in
vivo. Nanotube-Ti mesh coated with hydroxyapatite/beta-tricalcium phosphate
(HA/beta-TCP) was manufactured by an anodizing and a sintering method,
respectively. An 8 mm diameter defect was created on each acetabulum of eight
rabbits, then treated by grafting materials and covered by Ti meshes. At four and
eight weeks, postoperatively, biopsies were performed for histomorphometric
analyses. The newly-formed bone layers under cyclic precalcified anodized Ti (CP
AT) meshes were superior with regard to the mineralized area at both four and
eight weeks, as compared with that under untreated Ti meshes. Active bone
regeneration at 2-4 weeks was stronger than at 6-8 weeks, particularly with
treated biphasic ceramic (p < 0.05). CP improved the bioactivity of Ti meshes and
biphasic grafting materials. Moreover, the precalcified nanotubular Ti meshes
could enhance early contact bone formation on the mesh and, therefore, may reduce
the collapse of Ti meshes into the defect, increasing the sufficiency of
acetabular reconstruction. Finally, cyclic precalcification did not affect bone
regeneration by biphasic grafting materials in vivo.
PMID- 28686211
TI - Immunological and Inflammatory Impact of Non-Intubated Lung Metastasectomy.
AB - BACKGROUND: We hypothesized that video-assisted thoracic surgery (VATS) lung
metastasectomy under non-intubated anesthesia may have a lesser immunological and
inflammatory impact than the same procedure under general anesthesia. METHODS:
Between December 2005 and October 2015, 55 patients with pulmonary
oligometastases (at the first episode) successfully underwent VATS metastasectomy
under non-intubated anesthesia. Lymphocytes subpopulation and interleukins 6 and
10 were measured at different intervals and matched with a control group composed
of 13 patients with similar clinical features who refused non-intubated surgery.
RESULTS: The non-intubated group demonstrated a lesser reduction of natural
killer lymphocytes at 7 days from the procedure (p = 0.04) compared to control.
Furthermore, the group revealed a lesser spillage of interleukin 6 after 1 (p =
0.03), 7 (p = 0.04), and 14 (p = 0.05) days. There was no mortality in any
groups. Major morbidity rate was significantly higher in the general anesthesia
group 3 (5%) vs. 3 (23%) (p = 0.04). The median hospital stay was 3.0 vs. 3.7 (p
= 0.033) days, the estimated costs with the non-intubated procedure was
significantly lower, even excluding the hospital stay. CONCLUSIONS: VATS lung
metastasectomy in non-intubated anesthesia had significantly lesser impact on
both immunological and inflammatory response compared to traditional procedure in
intubated general anesthesia.
PMID- 28686213
TI - A Study of Vicon System Positioning Performance.
AB - Motion capture setups are used in numerous fields. Studies based on motion
capture data can be found in biomechanical, sport or animal science. Clinical
science studies include gait analysis as well as balance, posture and motor
control. Robotic applications encompass object tracking. Today's life
applications includes entertainment or augmented reality. Still, few studies
investigate the positioning performance of motion capture setups. In this paper,
we study the positioning performance of one player in the optoelectronic motion
capture based on markers: Vicon system. Our protocol includes evaluations of
static and dynamic performances. Mean error as well as positioning variabilities
are studied with calibrated ground truth setups that are not based on other
motion capture modalities. We introduce a new setup that enables directly
estimating the absolute positioning accuracy for dynamic experiments contrary to
state-of-the art works that rely on inter-marker distances. The system performs
well on static experiments with a mean absolute error of 0.15 mm and a
variability lower than 0.025 mm. Our dynamic experiments were carried out at
speeds found in real applications. Our work suggests that the system error is
less than 2 mm. We also found that marker size and Vicon sampling rate must be
carefully chosen with respect to the speed encountered in the application in
order to reach optimal positioning performance that can go to 0.3 mm for our
dynamic study.
PMID- 28686212
TI - Raman Plus X: Biomedical Applications of Multimodal Raman Spectroscopy.
AB - Raman spectroscopy is a label-free method of obtaining detailed chemical
information about samples. Its compatibility with living tissue makes it an
attractive choice for biomedical analysis, yet its translation from a research
tool to a clinical tool has been slow, hampered by fundamental Raman scattering
issues such as long integration times and limited penetration depth. In this
review we detail the how combining Raman spectroscopy with other techniques
yields multimodal instruments that can help to surmount the translational
barriers faced by Raman alone. We review Raman combined with several optical and
non-optical methods, including fluorescence, elastic scattering, OCT, phase
imaging, and mass spectrometry. In each section we highlight the power of each
combination along with a brief history and presentation of representative
results. Finally, we conclude with a perspective detailing both benefits and
challenges for multimodal Raman measurements, and give thoughts on future
directions in the field.
PMID- 28686214
TI - Current Study of the Mechanism of Action of the Potential Anti-Epileptic Agent
Q808.
AB - Our previous study showed that the anticonvulsant Q808 might be effective against
seizures induced by maximal electroshock, pentylenetetrazole (PTZ), isoniazid
(ISO), thiosemicarbazide (THIO), and 3-mercaptopropionic acid (3-MP). In the
present study, we explored the possible mechanism of action of Q808. Results
obtained with high-performance liquid chromatography (HPLC) suggest that Q808 may
affect neurotransmitter content in the brain, by specifically increasing GABA
content in the rat hippocampus at doses of 40 mg/kg and 80 mg/kg, and by reducing
the content of glutamate and glutamine in the rat thalamus at a dose of 80 mg/kg.
Intriguingly, there were no changes in the neurotransmitter content in the cortex
in response to Q808. In vitro brain slice electrophysiological studies showed
that 10-5 M Q808 enhanced the frequency of spontaneous inhibitory postsynaptic
currents (sIPSCs) in corn cells of the CA1 area of the hippocampus, and had no
effect on the amplitude of sIPSCs, the frequency and amplitude of spontaneous
excitatory postsynaptic currents (sEPSCs), or gamma-aminobutyric acid (GABA)
receptor-mediated currents in primary cultured hippocampal neurons. These
findings suggest that the antiepileptic activity of Q808 may be due to its
ability to increase the amount of GABA between synapses, without affecting the
function of GABA receptors.
PMID- 28686215
TI - Health Impact of PM10, PM2.5 and Black Carbon Exposure Due to Different Source
Sectors in Stockholm, Gothenburg and Umea, Sweden.
AB - The most important anthropogenic sources of primary particulate matter (PM) in
ambient air in Europe are exhaust and non-exhaust emissions from road traffic and
combustion of solid biomass. There is convincing evidence that PM, almost
regardless of source, has detrimental health effects. An important issue in
health impact assessments is what metric, indicator and exposure-response
function to use for different types of PM. The aim of this study is to describe
sectorial contributions to PM exposure and related premature mortality for three
Swedish cities: Gothenburg, Stockholm and Umea. Exposure is calculated with high
spatial resolution using atmospheric dispersion models. Attributed premature
mortality is calculated separately for the main local sources and the
contribution from long-range transport (LRT), applying different relative risks.
In general, the main part of the exposure is due to LRT, while for black carbon,
the local sources are equally or more important. The major part of the premature
deaths is in our assessment related to local emissions, with road traffic and
residential wood combustion having the largest impact. This emphasizes the
importance to resolve within-city concentration gradients when assessing
exposure. It also implies that control actions on local PM emissions have a
strong potential in abatement strategies.
PMID- 28686217
TI - Meta-Analysis on Dietary Patterns and Pancreatic Cancer Risk: Methodological
Limitations.
AB - n/a.
PMID- 28686216
TI - Butyrate Reduces HFD-Induced Adipocyte Hypertrophy and Metabolic Risk Factors in
Obese LDLr-/-.Leiden Mice.
AB - Adipose tissue (AT) has a modulating role in obesity-induced metabolic
complications like type 2 diabetes mellitus (T2DM) via the production of so
called adipokines such as leptin, adiponectin, and resistin. The adipokines are
believed to influence other tissues and to affect insulin resistance, liver
function, and to increase the risk of T2DM. In this study, we examined the impact
of intervention with the short-chain fatty acid butyrate following a high-fat
diet (HFD) on AT function and other metabolic risk factors associated with
obesity and T2DM in mice during mid- and late life. In both mid- and late
adulthood, butyrate reduced HFD-induced adipocyte hypertrophy and elevations in
leptin levels, which were associated with body weight, and cholesterol and
triglyceride levels. HFD feeding stimulated macrophage accumulation primarily in
epididymal AT in both mid- and late life adult mice, which correlated with liver
inflammation in late adulthood. In late-adult mice, butyrate diminished increased
insulin levels, which were related to adipocyte size and macrophage content in
epididymal AT. These results suggest that dietary butyrate supplementation is
able to counteract HFD-induced detrimental changes in AT function and metabolic
outcomes in late life. These changes underlie the obesity-induced elevated risk
of T2DM, and therefore it is suggested that butyrate has potential to attenuate
risk factors associated with obesity and T2DM.
PMID- 28686219
TI - Do Inequalities in Neighborhood Walkability Drive Disparities in Older Adults'
Outdoor Walking?
AB - Older residents of high-deprivation areas walk less than those of low-deprivation
areas. Previous research has shown that neighborhood built environment may
support and encourage outdoor walking. The extent to which the built environment
supports and encourages walking is called "walkability". This study examines
inequalities in neighborhood walkability in high- versus low-deprivation areas
and their possible influences on disparities in older adults' outdoor walking
levels. For this purpose, it focuses on specific neighborhood built environment
attributes (residential density, land-use mix and intensity, street connectivity,
and retail density) relevant to neighborhood walkability. It applied a mixed
method approach, included 173 participants (>=65 years), and used a Geographic
Information System (GIS) and walking interviews (with a sub-sample) to
objectively and subjectively measure neighborhood built environment attributes.
Outdoor walking levels were measured by using the Geographic Positioning System
(GPS) technology. Data on personal characteristics was collected by completing a
questionnaire. The results show that inequalities in certain land-use intensity
(i.e., green spaces, recreation centers, schools and industries) in high- versus
low-deprivation areas may influence disparities in older adults' outdoor walking
levels. Modifying neighborhood land use intensity may help to encourage outdoor
walking in high-deprivation areas.
PMID- 28686220
TI - The Association between Non-Alcoholic Fatty Liver Disease and Cardiovascular Risk
in Children.
AB - The rising prevalence of childhood obesity in the past decades has made Non
Alcoholic Fatty Liver Disease (NAFLD) the most common cause of pediatric chronic
liver disease worldwide. Currently, a growing body of evidence links NAFLD with
cardiovascular disease (CVD) even at an early age. Data on the pediatric
population have shown that NAFLD could represent an independent risk factor not
only for cardiovascular events but also for early subclinical abnormalities in
myocardial structure and function. Briefly, we review the current knowledge
regarding the relationship between pediatric NAFLD and cardiovascular risk in an
attempt to clarify our understanding of NAFLD as a possible cardiovascular risk
factor in childhood.
PMID- 28686218
TI - Lysosomal Regulation of mTORC1 by Amino Acids in Mammalian Cells.
AB - The mechanistic target of rapamycin complex 1 (mTORC1) is a master regulator of
cell growth in eukaryotic cells. The active mTORC1 promotes cellular anabolic
processes including protein, pyrimidine, and lipid biosynthesis, and inhibits
catabolic processes such as autophagy. Consistent with its growth-promoting
functions, hyper-activation of mTORC1 signaling is one of the important
pathomechanisms underlying major human health problems including diabetes,
neurodegenerative disorders, and cancer. The mTORC1 receives multiple upstream
signals such as an abundance of amino acids and growth factors, thus it regulates
a wide range of downstream events relevant to cell growth and proliferation
control. The regulation of mTORC1 by amino acids is a fast-evolving field with
its detailed mechanisms currently being revealed as the precise picture emerges.
In this review, we summarize recent progress with respect to biochemical and
biological findings in the regulation of mTORC1 signaling on the lysosomal
membrane by amino acids.
PMID- 28686221
TI - Evaluation of Cyanea capillata Sting Management Protocols Using Ex Vivo and In
Vitro Envenomation Models.
AB - Lion's mane jellyfish (Cyanea capillata) stings cause severe pain and can lead to
dangerous systemic effects, including Irukandji-like syndrome. As is the case for
most cnidarian stings, recommended medical protocols in response to such stings
lack rigorous scientific support. In this study, we sought to evaluate potential
first aid care protocols using previously described envenomation models that
allow for direct measurements of venom activity. We found that seawater rinsing,
the most commonly recommended method of tentacle removal for this species,
induced significant increases in venom delivery, while rinsing with vinegar or
Sting No More(r) Spray did not. Post-sting temperature treatments affected sting
severity, with 40 min of hot-pack treatment reducing lysis of sheep's blood (in
agar plates), a direct representation of venom load, by over 90%. Ice pack
treatment had no effect on sting severity. These results indicate that sting
management protocols for Cyanea need to be revised immediately to discontinue
rinsing with seawater and include the use of heat treatment.
PMID- 28686223
TI - Regulation of Autophagy through TORC1 and mTORC1.
AB - Autophagy is an intracellular protein-degradation process that is conserved
across eukaryotes including yeast and humans. Under nutrient starvation
conditions, intracellular proteins are transported to lysosomes and vacuoles via
membranous structures known as autophagosomes, and are degraded. The various
steps of autophagy are regulated by the target of rapamycin complex 1
(TORC1/mTORC1). In this review, a history of this regulation and recent advances
in such regulation both in yeast and mammals will be discussed. Recently, the
mechanism of autophagy initiation in yeast has been deduced. The autophagy
related gene 13 (Atg13) and the unc-51 like autophagy activating kinase 1 (Ulk1)
are the most crucial substrates of TORC1 in autophagy, and by its
dephosphorylation, autophagosome formation is initiated.
Phosphorylation/dephosphorylation of Atg13 is regulated spatially inside the
cell. Another TORC1-dependent regulation lies in the expression of autophagy
genes and vacuolar/lysosomal hydrolases. Several transcriptional and post
transcriptional regulations are controlled by TORC1, which affects autophagy
activity in yeast and mammals.
PMID- 28686222
TI - Multiple Sclerosis: Immunopathology and Treatment Update.
AB - The treatment of multiple sclerosis (MS) has changed over the last 20 years. All
immunotherapeutic drugs target relapsing remitting MS (RRMS) and it still remains
a medical challenge in MS to develop a treatment for progressive forms. The most
common injectable disease-modifying therapies in RRMS include beta-interferons 1a
or 1b and glatiramer acetate. However, one of the major challenges of injectable
disease-modifying therapies has been poor treatment adherence with approximately
50% of patients discontinuing the therapy within the first year. Herein, we go
back to the basics to understand the immunopathophysiology of MS to gain insights
in the development of new improved drug treatments. We present current disease
modifying therapies (interferons, glatiramer acetate, dimethyl fumarate,
teriflunomide, fingolimod, mitoxantrone), humanized monoclonal antibodies
(natalizumab, ofatumumb, ocrelizumab, alentuzumab, daclizumab) and emerging
immune modulating approaches (stem cells, DNA vaccines, nanoparticles, altered
peptide ligands) for the treatment of MS.
PMID- 28686224
TI - A Balanced Risk-Benefit Analysis to Determine Human Risks Associated with
Pyrrolizidine Alkaloids (PA)-The Case of Tea and Herbal Infusions.
AB - Humans are exposed to pyrrolizidine alkaloids (PA) through different sources,
mainly from contaminated foodstuff. Teas and herbal infusions (T&HI) can be
contaminated by PA producing weed. PA can possess toxic, mutagenic, genotoxic,
and carcinogenic properties. Thus, possible health risks for the general
population are under debate. There is a strong safety record for T&HI and
additionally epidemiological evidence for the preventive effects of regular tea
consumption on cardiovascular events and certain types of cancer. There is no
epidemiological evidence, however, for human risks of regular low dose PA
exposure. Recommended regulatory PA-threshold values are based on experimental
data only, accepting big uncertainties. If a general risk exists through PA
contaminated T&HI, it must be small compared to other frequently accepted risks
of daily living and the proven health effects of T&HI. Decision making should be
based on a balanced riskbenefit analysis. Based on analyses of the scientific
data currently available, it is concluded that the benefits of drinking T&HI
clearly outweigh the negligible health risk of possible PA contamination. At the
same time, manufacturers must continue their efforts to secure good product
quality and to be transparent on their measures of quality control and risk
communication.
PMID- 28686227
TI - Human antibody pieces together the puzzle of the trimeric Lassa virus surface
antigen.
PMID- 28686226
TI - MYC is a positive regulator of choline metabolism and impedes mitophagy-dependent
necroptosis in diffuse large B-cell lymphoma.
AB - The activation of oncogenes can reprogram tumor cell metabolism. Here, in diffuse
large B-cell lymphoma (DLBCL), serum metabolomic analysis revealed that oncogenic
MYC could induce aberrant choline metabolism by transcriptionally activating the
key enzyme phosphate cytidylyltransferase 1 choline-alpha (PCYT1A). In B-lymphoma
cells, as a consequence of PCYT1A upregulation, MYC impeded lymphoma cells
undergo a mitophagy-dependent necroptosis. In DLBCL patients, overexpression of
PCYT1A was in parallel with an increase in tumor MYC, as well as a decrease in
serum choline metabolite phosphatidylcholine levels and an International
Prognostic Index, indicating intermediate-high or high risk. Both in vitro and in
vivo, lipid-lowering alkaloid berberine (BBR) exhibited an anti-lymphoma activity
through inhibiting MYC-driven downstream PCYT1A expression and inducing mitophagy
dependent necroptosis. Collectively, PCYT1A was upregulated by MYC, which
resulted in the induction of aberrant choline metabolism and the inhibition of B
lymphoma cell necroptosis. Referred as a biomarker for DLBCL progression, PCYT1A
can be targeted by BBR, providing a potential lipid-modifying strategy in
treating MYC-High lymphoma.
PMID- 28686229
TI - Open-door policies.
PMID- 28686225
TI - Retrospective Proteomic Screening of 100 Breast Cancer Tissues.
AB - The present investigation has been conducted on one hundred tissue fragments of
breast cancer, collected and immediately cryopreserved following the surgical
resection. The specimens were selected from patients with invasive ductal
carcinoma of the breast, the most frequent and potentially aggressive type of
mammary cancer, with the objective to increase the knowledge of breast cancer
molecular markers potentially useful for clinical applications. The proteomic
screening; by 2D-IPG and mass spectrometry; allowed us to identify two main
classes of protein clusters: proteins expressed ubiquitously at high levels in
all patients; and proteins expressed sporadically among the same patients. Within
the group of ubiquitous proteins, glycolytic enzymes and proteins with anti
apoptotic activity were predominant. Among the sporadic ones, proteins involved
in cell motility, molecular chaperones and proteins involved in the
detoxification appeared prevalent. The data of the present study indicates that
the primary tumor growth is reasonably supported by concurrent events: the
inhibition of apoptosis and stimulation of cellular proliferation, and the
increased expression of glycolytic enzymes with multiple functions. The second
phase of the evolution of the tumor can be prematurely scheduled by the
occasional presence of proteins involved in cell motility and in the defenses of
the oxidative stress. We suggest that this approach on large-scale 2D-IPG
proteomics of breast cancer is currently a valid tool that offers the opportunity
to evaluate on the same assay the presence and recurrence of individual proteins,
their isoforms and short forms, to be proposed as prognostic indicators and
susceptibility to metastasis in patients operated on for invasive ductal
carcinoma of the breast.
PMID- 28686228
TI - Switching dynein motors on and off.
PMID- 28686230
TI - Chromatin-enriched lncRNAs: a novel class of enhancer RNAs.
PMID- 28686233
TI - Your Life Made the Difference in How I Practice Medicine.
PMID- 28686232
TI - Superaging, the new phrenology, and the gluten-free diet for the brain.
PMID- 28686231
TI - Antimicrobial resistance in Neisseria gonorrhoeae: Global surveillance and a call
for international collaborative action.
AB - In a Policy Forum, Teodora Wi and colleagues discuss the challenges of
antimicrobial resistance in gonococci.
PMID- 28686234
TI - Opposing Maintenance of Certification (MOC) and the Interstate Medical Licensure
Compact.
PMID- 28686235
TI - Results from a Community-Wide Pilot Program to Standardize COPD Education for
Patients Across Healthcare Settings in Rhode Island.
AB - Chronic obstructive pulmonary disease (COPD) is associated with significant
morbidity, decreased quality of life, and burdensome hospital admissions.
Therefore, patients with COPD interact with clinicians in a number of healthcare
settings. A coalition of healthcare practitioners in Rhode Island, in partnership
with the local Quality Improvement Organization, designed and implemented a
standardized, COPD education program for use across multiple healthcare settings.
More than 60 organizations participated, producing 140 Master Trainers, who
trained 634 staff members at their facilities from October 2015 through June
2016. Master Trainers were satisfied with the training, and we observed
significant increases in knowledge scores post-training among all participants,
which remained significant when stratified by setting. These results demonstrate
that implementation of a community-based program to disseminate patient-centered,
standardized COPD education in multiple healthcare settings is feasible. We hope
this program will ultimately improve patient outcomes and serve as the foundation
for expanding standardized education for other chronic conditions. [Full article
available at http://rimed.org/rimedicaljournal-2017-07.asp].
PMID- 28686236
TI - National Institutes of Health Funding in Rhode Island.
AB - OBJECTIVES: We present an overview of the National Institutes of Health (NIH)
funding in Rhode Island through analysis of 935 NIH grants received during the
fiscal years of 2012 to 2016. RESULTS: NIH funded over 2,600 grants from 2012 to
2016, of which approximately 900 were new grant awards, and the remainder were
annual grant renewals. The most funded type of research in Rhode Island is mental
health and substance abuse, followed by infectious disease, neurology, and public
health. Research funding of cardiovascular diseases, on a per capita basis, are
on par with the rest of the nation, while cancer research funding is less than
one half the national average. The largest NIH institutional funding source is
the National Institute of General Medical Sciences (NIGMS), followed by National
Institute of Mental Health (NIMH) and National Institute on Alcohol Abuse and
Alcoholism (NIAAA). While research grants (R01s) remain the predominant source of
NIH funding, investigators in Rhode Island have secured additional funding
through program project (P) grants with the aim of bolstering research resources
and collaboration throughout the state. [Full article available at
http://rimed.org/rimedicaljournal-2017-07.asp].
PMID- 28686237
TI - Junk science for sale Sham journals proliferating online.
AB - A new danger threatens the integrity of scholarly publishing: predatory journals.
Internet-only, "open-access" publishing is a valid way for researchers to reach
the public without a paywall separating them. But, of thousands of open-access
scientific journals today, as many as twenty-five percent are believed to be
fake, existing only to make money by charging authors high processing fees. In
sham journals, peer review is cursory or absent: as many as eighty to ninety
percent of submitted manuscripts are accepted, many within days, without any
editorial comment. Predatory journalism can be remarkably good at mimicking
reputable publishers. Sham journals use names and logos that closely resemble
those of legitimate journals, intentionally confusing site visitors.
Untrustworthy publications have not received the widespread, damning publicity
they deserve. If junk science is not confronted and eliminated, it will continue
to tarnish and undermine ethical, open-access scholarly publishing. [Full article
available at http://rimed.org/rimedicaljournal-2017-07.asp].
PMID- 28686238
TI - Practical Considerations for Prescribing Benzodiazepines and Opioids.
PMID- 28686239
TI - Spontaneous Rupture of the Spleen due to Infectious Mononucleosis.
PMID- 28686240
TI - A sustainable synthesis of 2-aryl-3-carboxylate indolines from N-aryl enamines
under visible light irradiation.
AB - With visible light irradiation of a catalytic amount of Ir(ppy)3 at room
temperature, a number of N-aryl enamines were transformed into their
corresponding indoline products in good to excellent yields without requiring any
extra additives. This is the first example of the synthesis of indolines via the
intramolecular cyclization of enamines under visible light irradiation.
PMID- 28686241
TI - Nickel-catalysed direct alkylation of thiophenes via double C(sp3)-H/C(sp2)-H
bond cleavage: the importance of KH2PO4.
AB - A Ni-catalyzed oxidative C-H/C-H cross-dehydrogenative coupling (CDC) reaction
was developed for constructing various highly functionalized alkyl (aryl)
substituted thiophenes. This method employs thiophenes and aliphatic (aromatic)
amides that contain an 8-aminoquinoline as a removable directing group in the
presence of a silver oxidant. The approach enables the facile one-step synthesis
of substituted thiophenes with high functional group compatibility via double C-H
bond cleavage without affecting C-Br and C-I bonds. DFT calculations verify the
importance of KH2PO4 as an additive for promoting C-H bond cleavage and support
the involvement of a Ni(iii) species in the reaction.
PMID- 28686243
TI - Enhanced steady-state dissolution flux in reactive convective dissolution.
AB - Chemical reactions can accelerate, slow down or even be at the very origin of the
development of dissolution-driven convection in partially miscible
stratifications when they impact the density profile in the host fluid phase. We
numerically analyze the dynamics of this reactive convective dissolution in the
fully developed non-linear regime for a phase A dissolving into a host layer
containing a dissolved reactant B. We show for a general A + B -> C reaction in
solution, that the dynamics vary with the Rayleigh numbers of the chemical
species, i.e. with the nature of the chemicals in the host phase. Depending on
whether the reaction slows down, accelerates or is at the origin of the
development of convection, the spatial distributions of species A, B or C, the
dissolution flux and the reaction rate are different. We show that chemical
reactions can enhance the steady-state flux as they consume A and can induce more
intense convection than in the non-reactive case. This result is important in the
context of CO2 geological sequestration where quantifying the storage rate of CO2
dissolving into the host oil or aqueous phase is crucial to assess the efficiency
and the safety of the project.
PMID- 28686242
TI - Keratin: dissolution, extraction and biomedical application.
AB - Keratinous materials such as wool, feathers and hooves are tough unique
biological co-products that usually have high sulfur and protein contents. A high
cystine content (7-13%) differentiates keratins from other structural proteins,
such as collagen and elastin. Dissolution and extraction of keratin is a
difficult process compared to other natural polymers, such as chitosan, starch,
collagen, and a large-scale use of keratin depends on employing a relatively
fast, cost-effective and time efficient extraction method. Keratin has some
inherent ability to facilitate cell adhesion, proliferation, and regeneration of
the tissue, therefore keratin biomaterials can provide a biocompatible matrix for
regrowth and regeneration of the defective tissue. Additionally, due to its amino
acid constituents, keratin can be tailored and finely tuned to meet the exact
requirement of degradation, drug release or incorporation of different
hydrophobic or hydrophilic tails. This review discusses the various methods
available for the dissolution and extraction of keratin with emphasis on their
advantages and limitations. The impacts of various methods and chemicals used on
the structure and the properties of keratin are discussed with the aim of
highlighting options available toward commercial keratin production. This review
also reports the properties of various keratin-based biomaterials and critically
examines how these materials are influenced by the keratin extraction procedure,
discussing the features that make them effective as biomedical applications, as
well as some of the mechanisms of action and physiological roles of keratin.
Particular attention is given to the practical application of keratin
biomaterials, namely addressing the advantages and limitations on the use of
keratin films, 3D composite scaffolds and keratin hydrogels for tissue
engineering, wound healing, hemostatic and controlled drug release.
PMID- 28686244
TI - 3D printed porous ceramic scaffolds for bone tissue engineering: a review.
AB - This study summarizes the recent research status and development of three
dimensional (3D)-printed porous ceramic scaffolds in bone tissue engineering.
Recent literature on 3D-printed porous ceramic scaffolds was reviewed. Compared
with traditional processing and manufacturing technologies, 3D-printed porous
ceramic scaffolds have obvious advantages, such as enhancement of the
controllability of the structure or improvement of the production efficiency.
More sophisticated scaffolds were fabricated by 3D printing technology. 3D
printed bioceramics have broad application prospects in bone tissue engineering.
Through understanding the advantages and limitations of different 3D-printing
approaches, new classes of bone graft substitutes can be developed.
PMID- 28686245
TI - Expectations of food satiation and satiety reviewed with special focus on food
properties.
AB - Expectations of satiation are beliefs about the extent to which food is expected
to deliver fullness and expectation of satiety relates to the extent to which
food is expected to give respite from hunger and to inhibit further eating. In
recent years they have increasingly been investigated because of the interest in
how they can modulate energy intake. The present paper reviews the body of
research into concepts underlying these expectations, measurement methods and the
factors influencing their perception, with special focus on the sensory features
and composition of foods. Food science and technology can provide tools and
knowledge to aid in designing food with enhanced expectations of satiation and
satiety.
PMID- 28686246
TI - An inhibition mechanism of dihydromyricetin on tyrosinase and the joint effects
of vitamins B6, D3 or E.
AB - Dihydromyricetin (DMY), a natural flavonoid, was found to effectively inhibit
tyrosinase activity in a mixed-type manner with an IC50 value of (3.66 +/- 0.14)
* 10-5 mol L-1. DMY combined with the dietary vitamin D3 at lower concentrations
exhibited a synergistic effect on the inhibition of tyrosinase. The formation of
a DMY-tyrosinase complex led to fluorescence quenching and conformational changes
of tyrosinase, which was driven mainly by hydrophobic interactions and hydrogen
bonds. The molecular simulation further found that DMY inserted into the active
pocket of tyrosinase interacted with amino acid residues Tyr78, His85, and
Ala323, occupying the catalytic center of tyrosinase to hinder entrance of the
substrate, leading to the inhibition of tyrosinase. This study may provide a
scientific foundation for screening effective tyrosinase inhibitors.
PMID- 28686247
TI - DNA-surfactant complexes: self-assembly properties and applications.
AB - Over the last few years, DNA-surfactant complexes have gained traction as unique
and powerful materials for potential applications ranging from optoelectronics to
biomedicine because they self-assemble with outstanding flexibility spanning
packing modes from ordered lamellar, hexagonal and cubic structures to disordered
isotropic phases. These materials consist of a DNA backbone from which the
surfactants protrude as non-covalently bound side chains. Their formation is
electrostatically driven and they form bulk films, lyotropic as well as
thermotropic liquid crystals and hydrogels. This structural versatility and their
easy-to-tune properties render them ideal candidates for assembly in bulk films,
for example granting directional conductivity along the DNA backbone, for dye
dispersion minimizing fluorescence quenching allowing applications in lasing and
nonlinear optics or as electron blocking and hole transporting layers, such as in
LEDs or photovoltaic cells, owing to their extraordinary dielectric properties.
However, they do not only act as host materials but also function as a
chromophore itself. They can be employed within electrochromic DNA-surfactant
liquid crystal displays exhibiting remarkable absorptivity in the visible range
whose volatility can be controlled by the external temperature. Concomitantly,
applications in the biological field based on DNA-surfactant bulk films, liquid
crystals and hydrogels are rendered possible by their excellent gene and drug
delivery capabilities. Beyond the mere exploitation of their material properties,
DNA-surfactant complexes proved outstandingly useful for synthetic chemistry
purposes when employed as scaffolds for DNA-templated reactions, nucleic acid
modifications or polymerizations. These promising examples are by far not
exhaustive but foreshadow their potential applications in yet unexplored fields.
Here, we will give an insight into the peculiarities and perspectives of each
material and are confident to inspire future developments and applications
employing this emerging substance class.
PMID- 28686248
TI - Chalcogen bonding in synthesis, catalysis and design of materials.
AB - Chalcogen bonding is a type of noncovalent interaction in which a covalently
bonded chalcogen atom (O, S, Se or Te) acts as an electrophilic species towards a
nucleophilic (negative) region(s) in another or in the same molecule. In general,
this interaction is strengthened by the presence of an electron-withdrawing group
on the electron-acceptor chalcogen atom and upon moving down in the periodic
table of elements, from O to Te. Following a short discussion of the phenomenon
of chalcogen bonding, this Perspective presents some demonstrative experimental
observations in which this bonding is crucial for synthetic transformations,
crystal engineering, catalysis and design of materials as synthons/tectons.
PMID- 28686249
TI - Introductory lecture: atmospheric chemistry in the Anthropocene.
AB - The term "Anthropocene" was coined by Professor Paul Crutzen in 2000 to describe
an unprecedented era in which anthropogenic activities are impacting planet Earth
on a global scale. Greatly increased emissions into the atmosphere, reflecting
the advent of the Industrial Revolution, have caused significant changes in both
the lower and upper atmosphere. Atmospheric reactions of the anthropogenic
emissions and of those with biogenic compounds have significant impacts on human
health, visibility, climate and weather. Two activities that have had
particularly large impacts on the troposphere are fossil fuel combustion and
agriculture, both associated with a burgeoning population. Emissions are also
changing due to alterations in land use. This paper describes some of the
tropospheric chemistry associated with the Anthropocene, with emphasis on areas
having large uncertainties. These include heterogeneous chemistry such as those
of oxides of nitrogen and the neonicotinoid pesticides, reactions at liquid
interfaces, organic oxidations and particle formation, the role of sulfur
compounds in the Anthropocene and biogenic-anthropogenic interactions. A clear
and quantitative understanding of the connections between emissions, reactions,
deposition and atmospheric composition is central to developing appropriate cost
effective strategies for minimizing the impacts of anthropogenic activities. The
evolving nature of emissions in the Anthropocene places atmospheric chemistry at
the fulcrum of determining human health and welfare in the future.
PMID- 28686250
TI - Li2O2 as a cathode additive for the initial anode irreversibility compensation in
lithium-ion batteries.
AB - Commercially available Li2O2 was proposed as a cathode additive in commercialized
LiNi0.33Co0.33Mn0.33O2 (NCM) cathodes to offset the initial Li loss. Li2O2 can be
decomposed substantially under catalysis of NCM and leaves almost no remnants
after the Li compensation.
PMID- 28686251
TI - Oxygen-dependent activation of Cu,Zn-superoxide dismutase-1.
AB - Copper zinc superoxide dismutase (Sod1) is a critical enzyme in limiting reactive
oxygen species in both the cytosol and the mitochondrial intermembrane space.
Sod1 dismutes superoxide anions to hydrogen peroxide and oxygen. The catalytic
reaction is dependent on an active site copper ion and a disulfide bonded
conformation. The activation of Sod1 is mediated by its chaperone Ccs1. The
mechanism of Ccs1-mediated Sod1 activation involves both insertion of the
catalytic copper ion and mediating disulfide bond formation. Since Sod1 is a
highly abundant enzyme residing within the highly reducing cytoplasm, the
question of disulfide bond formation is significant yet unresolved. The processes
involved in Sod1 activation are reviewed with a focus on copper ion insertion and
disulfide bond formation.
PMID- 28686252
TI - Fourier-transform infrared spectroscopy for characterization of protein chain
reductions in enzymatic reactions.
AB - The potential of dry-film Fourier-transform infrared (FTIR) measurements as a
monitoring tool for enzymatic hydrolysis of protein-based substrates is explored
in this study. As a proof-of-concept, the enzymatic digestion of bovine serum
albumin using Alcalase was monitored. To evaluate the analytical approach on
complex substrates with industrial relevance, salmon- and chicken-based
substrates were digested for 80 minutes using Alcalase and a total of 12 FTIR
spectra were acquired during the course of the hydrolysis. The observed changes
in the IR spectral features as a function of hydrolysis time were found to be in
agreement with the breakdown of the amide backbone and formation of amino and
carboxylate terminals. Some of the most consistent markers for hydrolysis time
were the bands at 1516 cm-1 (-NH3+) and ~1400 cm-1 (-COO-). Moreover, principal
component analysis (PCA) of the FTIR spectra was used to demonstrate the
systematic relationship of the hydrolysis time with key variables (wavelengths)
in the protein backbone region (800-1800 cm-1). Scores in the first principal
component versus the hydrolysis time have been shown to provide an overview of
the process dynamics related to protein structural changes. The herein presented
results suggest that dry-film FTIR measurements have potential as a rapid tool
for monitoring industrial protein hydrolysis processes.
PMID- 28686253
TI - Predictive models of gas sorption in a metal-organic framework with open-metal
sites and small pore sizes.
AB - Simulations of CO2 and H2 sorption were performed in UTSA-20, a metal-organic
framework (MOF) having zyg topology and composed of Cu2+ ions coordinated to
3,3',3'',5,5',5''-benzene-1,3,5-triyl-hexabenzoate (BHB) linkers. Previous
experimental studies have shown that this MOF displays remarkable CO2 sorption
properties and exhibits one of the highest gravimetric H2 uptakes at 77 K/1.0 atm
(2.9 wt%) [Z. Guo, et al. Angew. Chem., Int. Ed., 2011, 50, 3178-3181]. For both
sorbates, the simulations were executed with the inclusion of explicit many-body
polarization interactions, which was necessary to reproduce sorption onto the
open-metal sites. Non-polarizable potentials were also utilized for simulations
of CO2 sorption as a control. The simulated excess sorption isotherms for both
CO2 and H2 are in very good agreement with the corresponding experimental data
over a wide range of temperatures and pressures, thus demonstrating the accuracy
and predictive power of the polarizable potentials used herein. The theoretical
isosteric heat of adsorption (Qst) values are also in good agreement with the
newly reported experimental Qst values for the respective sorbates in UTSA-20.
Sorption onto the more positively charged Cu2+ ion of the [Cu2(O2CR)4] cluster
was observed for both CO2 and H2. However, a binding site with energetics
comparable to that for an open-metal site was also discovered for both sorbates.
A radial distribution function (g(r)) analysis about the preferential Cu2+ ions
for CO2 and H2 revealed that both sorbates display different trends for the
relative occupancy about such sites upon increasing/decreasing the pressure in
the MOF. Overall, this study provides insights into the CO2 and H2 sorption
mechanisms in this MOF containing open-metal sites and small pore sizes for the
first time through a classical polarizable force field.
PMID- 28686254
TI - Thermodynamics of chemical Marangoni-driven engines.
AB - The goal of this paper is to perform a general thermodynamic study of Marangoni
driven engines in which chemical energy is directly transformed into mechanical
motion. Given that this topic has not been discussed before, we will explore here
the most basic and fundamental aspects of the phenomena at work, which leads to a
number of interesting observations typical of controversies in classical
thermodynamics. Starting with a discussion of a few key motivating examples of
chemical Marangoni-driven phenomena - tears of wine, an oscillating pendant
droplet, "beating" oil lens, and traveling waves in a circular container - and
contrasting homogeneous versus inhomogeneous thermodynamic systems we naturally
arrive at alternative ways of storing and generating energy with the help of
inhomogeneities in the bulk and surface properties of the working media. Of
particular interest here are systems with interfaces - hence, in this context we
discuss the nature and efficiency of the corresponding thermodynamic cycles
leading to work done as a result of a non-uniform distribution of surface
tension, which is in turn induced by a non-uniform surface active substance
(surfactant) distribution, for both soluble and insoluble surfactants. Based on
the relevant physical parameters of the working medium we can also evaluate the
isothermality, i.e. temperature variations, dissipative losses, energy output and
efficiency, entropy generation, and the period of such cycles in real processes.
The role of singularity formation at the interface for the existence of such
thermodynamic cycles is unraveled as well. Finally the discussion is concluded
with a few ideas for potential applications of Marangoni-driven engines.
PMID- 28686255
TI - Hemin/Au nanorods/self-doped TiO2 nanowires as a novel photoelectrochemical
bioanalysis platform.
AB - As a recently developed detection technique, photoelectrochemical (PEC)
measurement has received extensive attention. However, owing to the lack of a
comprehensive approach to engineer the photo-generated carriers, the performance
is still limited. As an example, a significant use of PEC measurement might be in
understanding the roles of glutathione in physiological and pathological
processes. Here, we developed a new approach for engineering the photo-generated
carriers with the aid of the synergic effect of self-doping, surface plasmon
resonance, electrical field amplification effect, etc. Thus, a highly sensitive
multicomponent PEC platform has been developed, in which Au nanorods are
decorated on the surface of self-doped TiO2 nanowires, followed by surface
receptor functionalization with hemin for capturing glutathione. The synergic
effect effectively increases generation, separation and transfer kinetics of the
photo-generated carriers, which can be further increased by using a mixture of Au
nanorods with different aspect ratios to tune the absorption wavelength to the
entire UV-visible region. As a result, this system exhibits a broad linear range
from 10 nM to 17.5 MUM and low detection limit down to 8.6 nM for detecting
glutathione, about 1-2 orders of magnitude lower than most existing PEC sensors.
PMID- 28686256
TI - Correction: Synthesis of l-rhamnose derived chiral bicyclic triazoles as novel
sodium-glucose transporter (SGLT) inhibitors.
AB - Correction for 'Synthesis of l-rhamnose derived chiral bicyclic triazoles as
novel sodium-glucose transporter (SGLT) inhibitors' by Siddamal Reddy Putapatri
et al., Org. Biomol. Chem., 2014, 12, 8415-8421.
PMID- 28686257
TI - An alkylating immobilization linker for immunochemical epigenetic assessment.
AB - A bifunctional linker molecule containing nitrogen mustard and a cyclic disulfide
group has been developed for the covalent immobilization of intact DNA, which
allows quantitative analysis of epigenomic modification in immobilized DNA using
SPR-based immune sensing.
PMID- 28686258
TI - Synthesis of oligoarylacetylenes with defined conjugated sequences using tailor
made soluble polymer supports.
AB - Due to their strong tendency to self-aggregate, unfunctionalized
oligoarylacetylenes are difficult to synthesize. Here, tailored polystyrene
soluble supports, prepared by atom transfer radical polymerization and post
polymerization modification, were tested for preparing sequence-defined
oligoarylacetylenes. Controlled aromatic sequences were obtained by iterative
Sonogarisha coupling, using phenyl- and pyridine-based building-blocks.
PMID- 28686259
TI - DDQ-promoted direct C5-alkylation of oxazoles with alkylboronic acids via
palladium-catalysed C-H bond activation.
AB - A novel and concise C5-alkylation of oxazoles using alkylboronic acids as alkyl
donors via Pd(ii)-catalysed C-H bond activation has been achieved in moderate to
good yields with satisfactory functional group tolerance. Instead of commonly
used BQ as a key promoter, DDQ was discovered to be a better additive that
significantly promoted this alkylation. This efficient and advanced method
represents the first C(sp2)-C(sp3) cross-coupling reaction at the C5-position of
oxazoles, which is particularly attractive due to its potential applications in
the late-stage functionalization of oxazole-containing bioactive molecules.
PMID- 28686260
TI - Mapping stress in polycrystals with sub-10 nm spatial resolution.
AB - From aircraft to electronic devices, and even in Formula One cars, stress is the
main cause of degraded material performance and mechanical failure in
applications incorporating thin films and coatings. Over the last two decades,
the scientific community has searched for the mechanisms responsible for stress
generation in films, with no consensus in sight. The main difficulty is that most
current models of stress generation, while atomistic in nature, are based on
macroscopic measurements. Here, we demonstrate a novel method for mapping the
stress at the surface of polycrystals with sub-10 nm spatial resolution. This
method consists of transforming elastic modulus maps measured by atomic force
microscopy techniques into stress maps via the local stress-stiffening effect.
The validity of this approach is supported by finite element modeling
simulations. Our study reveals a strongly heterogeneous distribution of intrinsic
stress in polycrystalline Au films, with gradients as high as 100 MPa nm-1 near
the grain boundaries. Consequently, our study discloses the limited capacity of
macroscopic stress assessments and standard tests to discriminate among models,
and the great potential of nanometer-scale stress mapping.
PMID- 28686261
TI - Synthesis of 1H-indole-3-sulfonates via palladium-catalyzed tandem reactions of 2
alkynyl arylazides with sulfonic acids.
AB - An efficient method for the synthesis of 1H-indole-3-sulfonates via palladium
catalyzed tandem reactions of 2-alkynyl arylazides with sulfonic acids has been
developed. The desired products were obtained in good to excellent yields under
mild reaction conditions. The reactions were shown to proceed very fast, in most
cases, within 10 min.
PMID- 28686262
TI - Transcription dynamics stabilizes nucleus-like layer structure in chromatin
brush.
AB - We use a brush of DNA in a solution of transcriptional machinery and histone
proteins to theoretically predict that this brush shows phase separation due to
the instability arising from the disassembly of nucleosomes during transcription.
In the two-phase coexistent state, collapsed chains (with relatively large
nucleosome occupancy) lie at the grafting surface and swollen chains (with
relatively small nucleosome occupancy) are distributed at the space above the
collapsed chains, analogous to the structure of chromatin in differentiated
cells. This layer structure is stabilized by the lateral osmotic pressure of
swollen chains. For a relatively small grafting density, DNA brushes show
tricritical points because the entropic elasticity with respect to the lateral
excursion of swollen chains balances with the lateral osmotic pressure of these
chains. At the tricritical points, DNA brushes show large fluctuations of local
nucleosome concentration, which may be reminiscent of the fluctuations observed
in embryonic stem cells.
PMID- 28686263
TI - One-pot mass preparation of MoS2/C aerogels for high-performance supercapacitors
and lithium-ion batteries.
AB - In this paper, we report the successful design and synthesis of a hierarchically
porous MoS2/C composite aerogel by simple one-pot mass preparation. The synthesis
involves the in situ formation of MoS2 nanosheets on agarose molecular chains,
the gelation of MoS2-deposited agarose monomers to generate a composite hydrogel,
and in situ transformation of the composite hydrogel into a MoS2/C composite
aerogel through carbonization. This composite aerogel can be used as a high
performance electrode material for supercapacitors and lithium-ion batteries.
When tested as a supercapacitor electrode, it achieves a high specific
capacitance of 712.6 F g-1 at 1 A g-1 and 97.3% capacity retention after 13 000
cycles at 6 A g-1. In addition, as a lithium-ion battery electrode, it exhibits a
superior rate capability (653.2 mA h g-1 at 0.1 A g-1 and 334.5 mA h g-1 at 5.0 A
g-1) and an ultrahigh capacity retention of nearly 100% after 1000 cycles at 1 A
g-1. These performances may be ascribed to the unique structure of the MoS2/C
composite aerogel, such as hierarchical pores, (002) plane-expanded MoS2 and
interconnected carbon networks embedded uniformly with MoS2 nanosheets. This work
may provide a general and simple approach for mass preparation of composite
aerogel materials and pave the way for promising materials applied in both
supercapacitors and lithium-ion batteries.
PMID- 28686264
TI - Curvature-induced microswarming.
AB - Like meridian lines on a globe, two lines on a Gaussian-curved surface cannot be
simultaneously straight and parallel everywhere. We find that this inescapable
property of Gaussian curvature has important consequences for the clustering and
swarming behavior of active matter. Focusing on the case of self-propelled
particles confined to the surface of a sphere, we find that for high curvature,
particles converge to a common orbit to form symmetry-breaking microswarms. We
prove that this microswarm flocking behavior is distinct from other known
examples in that it is a result of the curvature, and not incorporated through
Vicsek-like alignment rules or collision-induced torques. Additionally, we find
that clustering can be either enhanced or hindered as a consequence of both the
microswarming behavior and curvature-induced changes to the shape of a cluster's
boundary. Furthermore, we demonstrate how surfaces of non-constant curvature lead
to behaviors that are not explained by the simple averaging of the total
curvature. These observations demonstrate a promising method for engineering the
emergent behavior of active matter via the geometry of the environment.
PMID- 28686265
TI - Size-controlled CdSe quantum dots to boost light harvesting capability and
stability of perovskite photovoltaic cells.
AB - Here, we report that incorporation of size-controlled CdSe quantum dots (QDs)
into perovskite photovoltaic cells (PSCs) boosts their light harvesting
capability. X-ray photoemission and optical absorption spectroscopy analyses also
show that the electronic structure of CdSe QDs makes them efficient charge
transfer mediators between perovskite and Spiro-MeOTAD layers. In addition,
electrochemical impedance spectroscopy experiments demonstrate that QDs help to
decrease charge transfer resistance at the interfaces. Additionally, time
correlated single photon counting measurements show that small (2 nm) QDs enhance
visible light collection of PSCs in the short wavelength region via Forster
resonance energy transfer while large (4 nm) QDs improve light collection of PSCs
in the long wavelength region via enhanced light backscattering at the
perovskite/QD interface. Moreover, the photocurrent density in the PSCs with QDs
retained over 95% of the initial value in a 100 h stability test, thus supporting
that the perovskite layer that has been encapsulated with QDs acts to prevent
penetration of water molecules through the perovskite layer. Consequently, these
results support that utilization of size-controlled hybrid QDs could open up a
new route to realize high-performance PSCs even under humid conditions.
PMID- 28686266
TI - Mechanism of Pd-catalyzed acylation/alkenylation of aryl iodide: a DFT study.
AB - The Pd-catalyzed cross-coupling of aryl iodide, benzoic anhydride and ethyl
acrylate provided a useful alternative to synthesize alkenylated aryl ketones
with good selectivity and functional-group tolerance. In this manuscript, density
functional theory (DFT) calculations were performed to address the detailed
reaction mechanism. Computational results support the experimentally proposed
Pd(0)-Pd(ii)-Pd(iv) catalytic cycle and further clarify that the rate-determining
step is the oxidative addition of benzoic anhydride, the regioselectivity
determining step is the migratory insertion of ethyl acrylate and the following
beta-H elimination determines the stereoselectivity. The regioselectivity can be
attributed to the steric and electronic effect of ethyl acrylate and the
stereoselectivity can be explained by the steric repulsion between the toluene
moiety and the CO2Et moiety. Furthermore, we found that norbornene not only acts
as the removable scaffold in Catellani-Lautens-type reactions, but also plays the
role of suppressing the competitive migratory insertion of ethyl acetate.
Norbornene insertion and ethyl acetate insertion are found to have close free
energy barriers, which shed light on the origin of using stoichiometric amounts
of norbornene.
PMID- 28686267
TI - Growth of germanium on Au(111): formation of germanene or intermixing of Au and
Ge atoms?
AB - We studied the growth of Ge layers on Au(111) under ultra-high vacuum conditions
from the submonolayer regime up to a few layers with Scanning Tunneling
Microscopy (STM), Direct Recoiling Spectroscopy (DRS) and Low Energy Electron
Diffraction (LEED). Most STM images for the thicker layers are consistent with a
commensurate 5 * 8 arrangement. The high surface sensitivity of TOF-DRS allows us
to confirm the coexistence of Au and Ge atoms in the top layer for all stages of
growth. An estimation of the Au to Ge ratio at the surface of the thick layer
gives about 1 Au atom per 2 Ge ones. When the growth is carried out at sample
temperatures higher than about 420 K, a fraction of the deposited Ge atoms
migrate into the bulk of Au. This incorporation of Ge into the bulk reduces the
growth rate of the Ge films, making it more difficult to obtain films thicker
than a few layers. After sputtering the Ge/Au surface, the segregation of bulk Ge
atoms to the surface occurs for temperatures >=600 K. The surface obtained after
segregation of Ge reaches a stable condition (saturation) with an n * n symmetry
with n on the order of 14.
PMID- 28686268
TI - SmI2-mediated reductive cyclization of beta-arylthio ketones: a facile and
diastereoselective synthesis of thiochroman derivatives.
AB - SmI2-mediated reductive cyclization of beta-arylthio ketones to generate
thiochroman derivatives is not a generally observed process and the reported
examples are limited to geminal disubstitution in the substrates. The results of
the current study show that the cyclization also occurs when other substitution
patterns are present, affording a general approach to dihydrothiochroman-ols in
good yields and high degrees of diastereoselectivity. Besides, the halogen
substitution on beta-aryl is tolerated in most cases here although reductive
dehalogenation has been reported to predominate in the reductive cyclization
process. Dihydrothiochroman-4-ols were readily oxidized to thiochroman-4-ols in
almost quantitative yields.
PMID- 28686270
TI - Regioselective Diels-Alder reaction to open-cage ketolactam derivatives of C60.
AB - Open-cage ketolactam fullerenes reacted with dienes on the rim of the orifice
both regio- and stereoselectively. Unequivocal evidence for the structure of the
Diels-Alder adduct was provided by 2D INADEQUATE 13C NMR studies on 13C enriched
material, as well as via DFT-GIAO calculations. The theoretical calculations
successfully model the regioselective and the endo stereoselective reaction,
predicting molecular orbital control along with a repulsive steric interaction
between the substituents on the nitrogen atom and those on the diene.
PMID- 28686271
TI - Synthesis of pyrrolidine-3-carboxylic acid derivatives via asymmetric Michael
addition reactions of carboxylate-substituted enones.
AB - To concisely synthesize highly enantiomerically enriched 5-alkyl-substituted
pyrrolidine-3-carboxylic acids, organocatalytic enantioselective Michael addition
reactions of 4-alkyl-substituted 4-oxo-2-enoates with nitroalkanes have been
developed. Using the developed reaction method, 5-methylpyrrolidine-3-carboxylic
acid with 97% ee was obtained in two steps.
PMID- 28686269
TI - Iron homeostasis in plants - a brief overview.
AB - Iron plays a crucial role in biochemistry and is an essential micronutrient for
plants and humans alike. Although plentiful in the Earth's crust it is not
usually found in a form readily accessible for plants to use. They must therefore
sense and interact with their environment, and have evolved two different
molecular strategies to take up iron in the root. Once inside, iron is complexed
with chelators and distributed to sink tissues where it is used predominantly in
the production of enzyme cofactors or components of electron transport chains.
The processes of iron uptake, distribution and metabolism are overseen by tight
regulatory mechanisms, at the transcriptional and post-transcriptional level, to
avoid iron concentrations building to toxic excess. Iron is also loaded into
seeds, where it is stored in vacuoles or in ferritin. This is important for human
nutrition as seeds form the edible parts of many crop species. As such,
increasing iron in seeds and other tissues is a major goal for biofortification
efforts by both traditional breeding and biotechnological approaches.
PMID- 28686272
TI - Technetium complexes with arylselenolato and aryltellurolato ligands.
AB - Reactions of (NBu4)[TcOCl4] or [TcCl3(PPh3)2(CH3CN)] with in situ-prepared
lithium arylselenolates and -tellurolates give (NBu4)[TcVO(ArE)4] (E = Se, Te; Ar
= phenyl) and [TcIII(ArE)3(PPh3)(CH3CN)] (E = Se, Te; Ar = phenyl, 2,6-Me2phenyl,
mesityl) complexes, respectively. The products contain square-pyramidal (TcV
compounds) and trigonal bipyramidal (TcIII complexes) coordinated technetium
atoms. Density functional theory calculations indicate that the Tc-chalcogen
bonds in the TcIII compounds have a greater bond order than those in the TcV
compounds.
PMID- 28686273
TI - Photosensitizer (PS)/polyhedral oligomeric silsesquioxane (POSS)-crosslinked
nanohybrids for enhanced imaging-guided photodynamic cancer therapy.
AB - Photodynamic therapy (PDT) has drawn extensive attention as a promising cancer
treatment modality. However, most PDT nanoagents suffer from insufficient drug
loading capacity, a severe self-quenching effect, premature release of drugs
and/or potential toxicity. Herein, we rationally designed an inorganic-organic
nanohybrid with high drug loading capacity and superior chemical stability for
enhanced PDT. Polyhedral oligomeric silsesquioxane (POSS), an amine-containing
cage-shaped building block, was crosslinked with chlorin e6 (Ce6), a carboxyl
containing photosensitizer, via the amine-carboxyl reaction. Polyethylene glycol
(PEG) polymers were further modified on the surface of the nanoparticle to
improve the aqueous dispersibility and prolong the circulation time of the final
nanoconstruct (POSS-Ce6-PEG). The as-prepared POSS-Ce6-PEG has a considerably
high loading rate of Ce6 (19.8 wt%) with desirable fluorescence emission and
singlet oxygen generation. Besides, in vitro experiments revealed that the
nanoagent exhibited enhanced cellular uptake and a preferred intracellular
accumulation within mitochondria and the endoplasmic reticulum, resulting in high
anticancer efficiency under light irradiation. Furthermore, in vivo imaging
guided PDT was also successfully achieved, showing the effective tumor targeting
and ablation ability of POSS-Ce6-PEG. More importantly, the nanoagent possesses
negligible dark cytotoxicity and systemic side effects. Therefore, POSS-Ce6-PEG
as an eligible PDT theranostic agent holds great potential in clinical
applications.
PMID- 28686274
TI - Spectroscopic and computational studies of reversible O2 binding by a cobalt
complex of relevance to cysteine dioxygenase.
AB - The substitution of non-native metal ions into metalloenzyme active sites is a
common strategy for gaining insights into enzymatic structure and function. For
some nonheme iron dioxygenases, replacement of the Fe(ii) center with a redox
active, divalent transition metal (e.g., Mn, Co, Ni, Cu) gives rise to an enzyme
with equal or greater activity than the wild-type enzyme. In this manuscript, we
apply this metal-substitution approach to synthetic models of the enzyme cysteine
dioxygenase (CDO). CDO is a nonheme iron dioxygenase that initiates the
catabolism of l-cysteine by converting this amino acid to the corresponding
sulfinic acid. Two mononuclear Co(ii) complexes (3 and 4) have been prepared with
the general formula [Co2+(TpR2)(CysOEt)] (R = Ph (3) or Me (4); TpR2 =
hydrotris(pyrazol-1-yl)borate substituted with R-groups at the 3- and 5
positions, and CysOEt is the anion of l-cysteine ethyl ester). These Co(ii)
complexes mimic the active-site structure of substrate-bound CDO and are
analogous to functional iron-based CDO models previously reported in the
literature. Characterization with X-ray crystallography and/or 1H NMR
spectroscopy revealed that 3 and 4 possess five-coordinate structures featuring
facially-coordinating TpR2 and S,N-bidentate CysOEt ligands. The electronic
properties of these high-spin (S = 3/2) complexes were interrogated with UV
visible absorption and X-band electron paramagnetic resonance (EPR)
spectroscopies. The air-stable nature of complex 3 replicates the inactivity of
cobalt-substituted CDO. In contrast, complex 4 reversibly binds O2 at reduced
temperatures to yield an orange chromophore (4-O2). Spectroscopic (EPR, resonance
Raman) and computational (density functional theory, DFT) analyses indicate that
4-O2 is a S = 1/2 species featuring a low-spin Co(iii) center bound to an end-on
(eta1) superoxo ligand. DFT calculations were used to evaluate the energetics of
key steps in the reaction mechanism. Collectively, these results have elucidated
the role of electronic factors (e.g., spin-state, d-electron count, metal-ligand
covalency) in facilitating O2 activation and S-dioxygenation in CDO and related
models.
PMID- 28686275
TI - Power-dependent upconversion quantum yield of NaYF4:Yb3+,Er3+ nano- and
micrometer-sized particles - measurements and simulations.
AB - Photophysical studies of nonlinear lanthanide-doped photon upconverting
nanoparticles (UCNPs) increasingly used in biophotonics and photovoltaics require
absolute measurements of the excitation power density (P)-dependent upconversion
luminescence (UCL) and luminescence quantum yields (PhiUC) for quantifying the
material performance, UCL deactivation pathways, and possible enhancement
factors. We present here the P-dependence of the UCL spectra, PhiUC, and slope
factors of the different emission bands of representative 25 nm-sized oleate
capped beta-NaYF4:17% Yb3+, 3% Er3+ UCNPs dispersed in toluene and as powder as
well as PhiUC of 3 MUm-sized upconversion particles (UCMUP), all measured with a
newly designed integrating sphere setup, enabling controlled variation of P over
four orders of magnitude. This includes quantifying the influence of the beam
shape on the measured PhiUC and comparison of experimental PhiUC with simulations
utilizing the balancing power density model of the Andersson-Engels group and the
simulated PhiUC of UCMUP from the Berry group, underpinned by closely matching
decay kinetics of our UC material. We obtained a maximum PhiUC of 10.5% for UCMUP
and a PhiUC of 0.6% and 2.1% for solid and dispersed UCNPs, respectively. Our
results suggest an overestimation of the contribution of the purple and an
underestimation of that of the red emission of beta-NaYF4:Yb3+,Er3+:
microparticles by the simulations of the Berry group. Moreover, our measurements
can be used as a guideline to the absolute determination of UCL and PhiUC.
PMID- 28686276
TI - Size dependent structural and polymorphic transitions in ZnO: from nanocluster to
bulk.
AB - We report on an extensive survey of (ZnO)N nanostructures ranging from bottom-up
generated nanoclusters to top-down nanoparticles cuts from bulk polymorphs. The
obtained results enable us to follow the energetic preferences of structure and
polymorphism in (ZnO)N systems with N varying between 10-1026. This size range
encompasses small nanoclusters with 10s of atoms and nanoparticles with 100s of
atoms, which we also compare with appropriate bulk limits. In all cases the
nanostructures and bulk systems are optimized using accurate all-electron,
relativistic density functional theory based calculations with numeric atom
centered orbital basis sets. Specifically, sets of five families of (ZnO)N
species are considered: single-layered and multi-layered nanocages, and bulk cut
nanoparticles from the sodalite (SOD), body centered tetragonal (BCT), and
wurtzite (WZ) ZnO polymorphs. Using suitable fits to interpolate and extrapolate
these data allows us to assess the size-dependent energetic stabilities of each
family. With increasing size our results indicate a progressive change in
energetic stability from single-layered to multi-layered cage-like nanoclusters.
For nanoparticles of around 2.6 nm diameter we identify a transitional region
where multi-layered cages, SOD, and BCT nanostructures are very similar in
energetic stability. This transition size also marks the size regime at which
bottom-up nanoclusters give way to top-down bulk-cut nanoparticles. Eventually, a
final crossover is found where the most stable WZ-ZnO polymorph begins to
energetically dominate at N ~ 2200. This size corresponds to an approximate
nanoparticle diameter of 4.7 nm, in line with experiments reporting the
observation of wurtzite crystallinity in isolated ligand-free ZnO nanoparticles
of 4-5 nm size or larger.
PMID- 28686277
TI - Toward the two-step microdynamic phase transition mechanism of an oligo(ethylene
glycol)methacrylate-based copolymer with a LCST-type poly(ionic liquid) block.
AB - A new LCST-type thermoresponsive polyelectrolyte P[P4,4,4,4][SS], poly(tetrabutyl
phosphonium styrene sulfonate), was introduced to PMEO2MA (poly(2-(2
methoxyethoxy)ethyl methacrylate)) via RAFT polymerization, in order to explore
the transition behavior of the block copolymer PMEO2MA-b-P[P4,4,4,4][SS] with two
distinct LCST-type segments. A relatively sharp LCST-type phase transition with
only one transition point is observed in the turbidity curves, while the whole
phase transition is completely different from the micro perspective. The phase
transition temperature range is relatively broad, according to the unsynchronized
changes of different protons of the two blocks in the temperature-variable 1H NMR
analysis. From PCMW analysis, it is found that there exists an obvious two-step
phase transition behavior, especially in the region of the C-H groups.
Accordingly, we divided the whole transition process into two subregions: 20-40
degrees C and 40-55 degrees C in 2Dcos analysis. At the first stage of 20-40
degrees C, the CH3 groups mainly belonging to the backbones of PMEO2MA blocks
have the earliest response to the heating and drive the first step of the
dehydration process of PMEO2MA-b-P[P4,4,4,4][SS], resulting in the formation of
an intermediate micelle state composed of the collapsed PMEO2MA core and
hydrophilic P[P4,4,4,4][SS] corona. In particular, the conformational changes and
the more compact structures due to the interaction between the C[double bond,
length as m-dash]O groups and P[P4,4,4,4][SS] segments (nu(C[double bond, length
as m-dash]OD2O-PILs)) were observed using IR analysis. With the continual
increase of the temperature, when the second temperature range of 40-55 degrees
C is reached, the P[P4,4,4,4][SS] segments start to collapse and expel the water
molecules, driven by the anions of the poly(ionic liquid)s, with the phosphonium
cations being distributed over the relatively hydrophilic outside.
PMID- 28686278
TI - Tunable white light of a Ce3+,Tb3+,Mn2+ triply doped Na2Ca3Si2O8 phosphor for
high colour-rendering white LED applications: tunable luminescence and energy
transfer.
AB - A tunable white light emitting Na2Ca3Si2O8:Ce3+,Tb3+,Mn2+ phosphor with a high
color rendering index (CRI) has been prepared. Under UV excitation,
Na2Ca3Si2O8:Ce3+ phosphors present blue luminescence and exhibit a broad
excitation ranging from 250 to 400 nm. When codoping Tb3+/Mn2+ ions into
Na2Ca3Si2O8, energy transfer from Ce3+ to Tb3+ and Ce3+ to Mn2+ ions is observed
from the spectral overlap between Ce3+ emission and Tb3+/Mn2+ excitation spectra.
The energy-transfer efficiencies and corresponding mechanisms are discussed in
detail. The mechanism of energy transfer from Ce3+ to Tb3+ is demonstrated to be
a dipole-quadrupole mechanism by the Inokuti-Hirayama model. The wavelength
tunable white light can be realized by coupling the emission bands centered at
440, 550 and 590 nm ascribed to the contribution from Ce3+, Tb3+ and Mn2+,
respectively. The commission on illumination value of color tunable emission can
be tuned by controlling the content of Ce3+, Tb3+ and Mn2+. Temperature-dependent
luminescence spectra proved the good thermal stability of the as-prepared
phosphor. White LEDs with CRI = 93.5 are finally fabricated using a 365 nm UV
chip and the as-prepared Na2Ca3Si2O8:Ce3+,Tb3+,Mn2+ phosphor. All the results
suggest that Na2Ca3Si2O8:Ce3+,Tb3+,Mn2+ can act as potential color-tunable and
single-phase white emission phosphors for possible applications in UV based white
LEDs.
PMID- 28686279
TI - Highlight on the solution processes occurring on silver(i)-assembling porphyrins
in the presence of an excess of silver salt.
AB - Coordination cages obtained upon complexation of pyridyl functionalized
porphyrins by Ag+ disassemble when overtaking a 1 : 2 stoichiometric amount of
silver salt. An excess of Ag+ then leads to unusual chemical processes, here
analyzed in detail, which permanently transform the monomeric porphyrins. The
observed processes, discussed with reference to model compounds devoid of
polyether substituted pyridyl residues, evidence a peculiar reactivity for meso
2,6-dimethylphenyl substituted porphyrins.
PMID- 28686280
TI - Spectral reading of optical resonance-encoded cells in microfluidics.
AB - The ability to label individual cells is useful for single-cell-level studies of
complex cellular interactions and heterogeneity. Optically readable cell labeling
is attractive as it can be investigated non-invasively and repeatedly at high
speeds. Here, we demonstrate the feasibility of large-scale cell barcoding and
identification using fluorescent polystyrene microbeads loaded into cells.
Intracellular beads with different diameters in a range of 5 to 12 MUm generate
spectrally distinguished features or barcodes. A microfluidic chip was used to
measure fluorescence resonance peaks emitted from individual cells. An algorithm
comparing the peak wavelengths to a reference barcode library allowed barcode
identification with high accuracy. This work provides a guideline to increase the
number of unique identifiers and reduce various false-positive and false-negative
errors.
PMID- 28686281
TI - Identification of microRNA precursors using reduced and hybrid features.
AB - MicroRNAs (also called miRNAs) are a group of short non-coding RNA molecules.
They play a vital role in the gene expression of transcriptional and post
transcriptional processes. However, abnormality of their expression has been
observed in cancer, heart diseases and nervous system disorders. Therefore for
basic research and microRNA based therapy, it is imperative to separate real pre
miRNAs from false ones (hairpin sequences similar to pre-miRNA stem loops).
Different conservation and machine learning methods have been applied for the
identification of miRNAs. However, machine learning algorithms have gained more
popularity than conservative based algorithms in terms of sensitivity and overall
performance. Due to the avalanche of RNA sequences discovered in a post-genomic
age, it is necessary to construct a predictor for the identification of pre
microRNAs in humans. We have developed a predictor called MicroR-Pred in which
the RNA sequences are formulated by a hybrid feature vector. The novelty of the
new predictor is in the use of the partial least squares technique followed by
the Random Forest and SVM (Support Vector Machine) algorithms for dimension
reduction and classification. The performance of the MicroR-Pred model is quite
promising compared to other state-of-the-art miRNA predictors. It has achieved
88.40% and 93.90% accuracies for RF and SVM.
PMID- 28686282
TI - Early maternal separation induces preference for sucrose and aspartame associated
with increased blood glucose and hyperactivity.
AB - Early life stress and exposure to sweeteners lead to physiological and behavioral
alterations in adulthood. Nevertheless, many genetic and environmental factors as
well as the neurobiological mechanisms that contribute to the development of
these disorders are not fully understood. Similarly, evidence about the long-term
metabolic effects of exposure to sweeteners in early life is limited and
inconsistent. This study used an animal model of maternal separation during
breastfeeding (MS) to analyze the effects of early life stress on consumption of
sweeteners, weight gain, blood glucose and locomotion. Rats were housed under a
reversed light/dark cycle (lights off at 7:00 h) with ad libitum access to water
and food. In the MS protocol, MS pups were separated from the dam for 6 h per day
in two periods of 180 minutes (7:00-10:00 and 13:00-16:00 h) during the dark
phase of postnatal day (PND) 1 to PND 21. Non-separated (NS) pups served as
controls. On PND 22 rats were grouped by sex and treatment. From PND 26 to PND 50
sucrose and aspartame were provided to rats, and sweetener intake, body weight
and blood glucose-related measures were scored. On PND 50, both male and female
rats were exposed to the open field test to obtain locomotion and anxiety-related
measures. Results showed that both early maternal separation and sweetener intake
during adolescence resulted in increased blood glucose and hyperactivity in male
rats but not in female rats. Data suggest that the combination of early stress
and exposure to sucrose and aspartame could be a risk factor for the development
of chronic diseases such as diabetes, as well as for behavioral alterations.
PMID- 28686283
TI - A reliable approach to prepare brittle semiconducting materials for cross
sectional transmission electron microscopy.
AB - Here, we present a sample preparation approach that simplifies the thinning of
very brittle wide bandgap semiconducting materials in cross-section geometry for
(scanning) transmission electron microscopy. Using AlN thin films grown on
sapphire and AlN substrates as case studies, we demonstrate that high-quality
samples can be routinely prepared while greatly reducing the preparation time and
consumables cost. The approach removes the sample preparation barrier to studying
a wide variety of materials by electron microscopy.
PMID- 28686285
TI - Toward a structural understanding of nucleic acid-sensing Toll-like receptors in
the innate immune system.
AB - The history of mankind has been plagued by the tug of war with viral infections.
Toll-like receptors (TLRs) and other receptors of the innate immune system
constitute an early defense system against invading viruses by recognizing the
viral genetic material, the nucleic acids (NAs). Agonistic ligands of NA-sensing
TLRs play an emerging role in the treatment of viral diseases, demonstrating a
crucial role of these receptors. Recently, crystal structures have afforded new
insights into TLR recognition of NAs. An aberrant activation by self-NAs, which
leads to the inflammation and autoimmunity, is avoided by strict regulation of NA
TLR interaction at multiple check-points. This Review summarizes the novel
structural understanding of NA-sensing by TLRs and regulatory mechanisms of these
receptors.
PMID- 28686286
TI - 3-D microstructure of olivine in complex geological materials reconstructed by
correlative X-ray MU-CT and EBSD analyses.
AB - We reconstruct the 3-D microstructure of centimetre-sized olivine crystals in
rocks from the Almirez ultramafic massif (SE Spain) using combined X-ray micro
computed tomography (MU-CT) and electron backscatter diffraction (EBSD). The
semidestructive sample treatment involves geographically oriented drill pressing
of rocks and preparation of oriented thin sections for EBSD from the MU-CT
scanned cores. The MU-CT results show that the mean intercept length (MIL)
analyses provide reliable information on the shape preferred orientation (SPO) of
texturally different olivine groups. We show that statistical interpretation of
crystal preferred orientation (CPO) and SPO of olivine becomes feasible because
the highest densities of the distribution of main olivine crystal axes from EBSD
are aligned with the three axes of the 3-D ellipsoid calculated from the MIL
analyses from MU-CT. From EBSD data we distinguish multiple CPO groups and by
locating the thin sections within the MU-CT volume, we assign SPO to the
corresponding olivine crystal aggregates, which confirm the results of
statistical comparison. We demonstrate that the limitations of both methods (i.e.
no crystal orientation data in MU-CT and no spatial information in EBSD) can be
overcome, and the 3-D orientation of the crystallographic axes of olivines from
different orientation groups can be successfully correlated with the crystal
shapes of representative olivine grains. Through this approach one can establish
the link among geological structures, macrostructure, fabric and 3-D SPO-CPO
relationship at the hand specimen scale even in complex, coarse-grained
geomaterials.
PMID- 28686284
TI - Maternal cortisol slope at 6 months predicts infant cortisol slope and EEG power
at 12 months.
AB - Physiological stress systems and the brain rapidly develop through infancy. While
the roles of caregiving and environmental factors have been studied, implications
of maternal physiological stress are unclear. We assessed maternal and infant
diurnal cortisol when infants were 6 and 12 months. We measured 12-month infant
electroencephalography (EEG) 6-9 Hz power during a social interaction. Steeper 6
month maternal slope predicted steeper 12-month infant slope controlling for 6
month infant slope and breastfeeding. Steeper 6-month maternal slope predicted
lower 6-9 Hz power. Six-month maternal area under the cuve (AUCg) was unrelated
to 12-month infant AUCg and 6-9 Hz power. Psychosocial, caregiving, and
breastfeeding variables did not explain results. At 6 months, maternal and infant
slopes correlated, as did maternal and infant AUCg. Twelve-month maternal and
infant cortisol were unrelated. Results indicate maternal slope is an informative
predictor of infant physiology and suggest the importance of maternal
physiological stress in this developmental period.
PMID- 28686287
TI - Food intake and darunavir plasma concentrations in people living with HIV in an
outpatient setting.
AB - AIMS: Patients receiving darunavir are advised to take it concomitantly with
food. The objectives of the present cross-sectional study were to evaluate the
actual concomitant food intake of patients visiting an HIV outpatient clinic.
METHODS: Sixty participants treated with darunavir/ritonavir once daily were
subjected to a food recall questionnaire concerning their last concomitant food
intake with darunavir. Darunavir trough concentrations were calculated. RESULTS:
The median food intake was 507 (0-2707) kcal; protein intake, 20 (0-221)g;
carbohydrate intake, 62 (0-267)g; fat intake: 14 (0-143)g; and dietary fibre: 4
(0-30)g. Twenty-five patients (42%) ingested their drug with between-meal snacks.
No relationship was found between food intake and trough concentrations.
CONCLUSIONS: Clear advice on the optimal caloric intake is needed, to avoid high
caloric intake in patients who already have an increased risk of cardiovascular
disease due to their HIV infection.
PMID- 28686289
TI - Ensuring the Comparability of Infant Mortality Rates: the Impact of the
Management of Pre-Viable and Peri-Viable Births.
PMID- 28686288
TI - Distribution of CYP2C8 and CYP2C9 amino acid substitution alleles in South Indian
diabetes patients: A genotypic and computational protein phenotype study.
AB - The CYP2C8 and CYP2C9 are two major isoforms of the cytochrome P450 enzyme
family, which is involved in drug response, detoxification, and disease
development. This study describes the differential distribution of amino acid
substitution variants of CYP2C8 (*2-I269F & *3-R139K) and CYP2C9 (*2-C144R & *3
L359A) genes in 234 type 2 diabetes mellitus (T2DM) patients and 218 healthy
controls from Andhra Pradesh, South India. Single locus genotype analysis has
revealed that homozygous recessive genotypes of 2C8*2-TT (P <= .03), 2C9*2-TT (P
<= .02), and heterozygous 2C9*3-AC (P <= .006) are seen to be increasingly
present in the case group, indicating a significant level of their association
with diabetes in Andhra population. The statistical significance of these
recessive genotypes has persisted even under their corresponding allelic forms (P
<= .01). Genotype association results were further examined by computational
protein structure and stability analysis to assess the deleteriousness of the
amino acid changes. The mutant CYP 2C8 and 2C9 (both *2 and *3) proteins showed
structural drifts at both amino acid residue (range 0.43A-0.77A), and polypeptide
chain levels (range 0.68A-1.81A) compared to their wild-type counterparts.
Furthermore, the free energy value differences (range -0.915 to -1.38 Kcal/mol)
between mutant and native protein structures suggests the deleterious and
destabilizing potential of amino acid substitution polymorphisms of CYP genes.
The present study confirms the variable distribution of CYP2C8 (*2 and *3) and
CYP2C9 (*2 and *3) allelic polymorphisms among South Indian diabetic populations
and further warrants the serious attention of CYP gene family, as a putative
locus for disease risk assessment and therapy.
PMID- 28686290
TI - Mining for mitochondrial mechanisms: Linking known syndromes to mitochondrial
function.
AB - Mitochondrial disorders (MDs) are caused by defects in 1 or multiple complexes of
the oxidative phosphorylation (OXPHOS) machinery. MDs are associated with a broad
range of clinical signs and symptoms, and have considerable clinical overlap with
other neuromuscular syndromes. This overlap might be due to involvement of
mitochondrial pathways in some of these non-mitochondrial syndromes. Here, we
give an overview of around 25 non-mitochondrial syndromes, diagnosed in patients
who were initially suspected to have a MD on the basis of clinical and
biochemical parameters. In addition, we highlight the mitochondrial connections
of 6 of these non-mitochondrial syndromes (eg, Rett syndrome and Dravet syndrome)
diagnosed in multiple patients. Further research to unravel the interplay between
these genes and mitochondria may help to increase knowledge on these syndromes.
Additionally, it may open new avenues for research on pathways interacting with
mitochondrial function in order to find new targets for therapeutics to treat
MDs. The data presented in this review underline the importance of careful
assessment of clinical, genetic, and biochemical data in all patients suspected
of a neuromuscular syndrome, and highlights the importance of the role of
clinical geneticists, physicians, and clinical biochemists in recognizing the
possible mitochondrial connection of non-mitochondrial syndromes.
PMID- 28686291
TI - Gonadal mosaicism and non-invasive prenatal diagnosis for 'reassurance' in
sporadic paternal age effect (PAE) disorders.
PMID- 28686292
TI - Microencapsulation of borage oil with blends of milk protein, beta-glucan and
maltodextrin through spray drying: physicochemical characteristics and stability
of the microcapsules.
AB - BACKGROUND: Borage oil is a rich commercial source of gamma-linolenic acid (18:3n
6). However, borage oil is rich in omega-6 polyunsaturated fatty acids and
vulnerable to oxidation. Thus, selecting appropriate wall materials is critical
to the encapsulation of borage oil. The present study investigated the influence
of wall materials on the physicochemical characteristics and stability of
microencapsulated borage oil by spray drying. Blends of milk protein [sodium
caseinate (CAS) or whey protein concentrate], beta-glucan (GLU) and maltodextrin
(MD) were used as the wall materials for encapsulating borage oil. RESULTS: The
microencapsulation of borage oil with different wall materials attained high
encapsulation efficiencies. The microencapsulated borage oil prepared with CAS-MD
achieved the optimal encapsulation efficiency of 96.62%. The oxidative
stabilities of borage oil and microencapsulated borage oil were measured by
accelerated storage test at 45 degrees C and 33% relative humidity for 30 days.
The microencapsulated borage oil presented lower peroxide values than those of
borage oil, and the microcapsules prepared with CAS-10GLU-MD (consisting of CAS
50 g kg-1 , GLU 100 g kg-1 and MD 475 g kg-1 of microencapsulation) conferred
borage oil with high protection against lipid oxidation. CONCLUSION: The results
of the present study demonstrate that the CAS-GLU-MD blend is appropriate for
microencapsulating borage oil. (c) 2017 Society of Chemical Industry.
PMID- 28686293
TI - Is primary hyperparathyroidism a cause of endothelial dysfunction?
AB - OBJECTIVE: Symptomatic primary hyperparathyroidism (PHPT) is thought to be
related to increased cardiovascular morbidity and mortality. In our study, we
aimed to investigate endothelial dysfunction and markers of subclinical
atherosclerosis in patients with PHPT. Also we aimed to demonstrate the effect of
vitamin D supplementation on these parameters. MATERIALS AND METHODS: Twenty-nine
patients followed by medical treatment (A), 25 preoperative (B) and 23
postoperative patients with PHPT (C), and 26 normocalcaemic subjects (D) were
included. Groups were assessed by measurements of flow-mediated dilation (FMD),
carotid intima-media thickness (CIMT), serum levels of sCD40L, high-sensitivity
CRP (hs-CRP) and interleukin-8 (IL-8). Thirteen patients with low levels of 25
hydroxy-vitamin D (25OHD) in the medical treatment group were assessed before and
3 months after vitamin D replacement. RESULTS: The median FMD was 5% in group A,
5.1% in group B, 7.6% in group C and 7.7% in group D. The FMD measurement in
group A was significantly lower than groups C and D (P=.02) and was similar to
the FMD measurement in group B. FMD measurements of group B were not
significantly lower than groups C and D. In 13 patients with low 25OHD in group
A, the median FMD increased to 7.07% from 4.71% after vitamin D replacement
(P=.02). CONCLUSION: Flow-mediated dilation was impaired in patients with PHPT,
particularly in the medically observed group. Vitamin D supplementation seems to
provide improvements in FMD in medically observed PHPT patients with low 25OHD
levels, and this was the novel observation of our study.
PMID- 28686295
TI - Effects of correcting in situ ruminal microbial colonization of feed particles on
the relationship between ruminally undegraded and intestinally digested crude
protein in concentrate feeds.
AB - BACKGROUND: In situ estimates of ruminally undegraded protein (RUP) and
intestinally digested protein (IDP) of ten concentrates, uncorrected or corrected
for the ruminal microbial colonization, were used to examine the effects of this
correction on the relationship between IDP and RUP values. Both variables were
established for three rumen and duodenum cannulated wethers using 15 N labeling
techniques and considering measured rates of ruminal particle comminution (kc )
and outflow (kp ). RESULTS: A covariance analysis showed that the close
relationship found between both variables (IDP = -0.0132 +/- 0.00679 + 0.776 +/-
0.0002 RUP; n = 60; P < 0.001; r = 0.960) is not affected by correcting for
microbial colonization (P = 0.682). CONCLUSION: The IDP content in concentrates
and industrial by-products can be predicted from RUP values, thus avoiding the
laborious and complex procedure of determining intestinal digestibility; however,
a larger sample of feeds is necessary to achieve more accurate predictions. The
lack of influence of the correction for microbial contamination on the prediction
observed in the present study increases the data available for this prediction.
However, only the use of corrected values may provide an accurate evaluation. (c)
2017 Society of Chemical Industry.
PMID- 28686294
TI - NFAT-regulated cytokine gene expression during tacrolimus therapy early after
renal transplantation.
AB - AIMS: Despite pharmacokinetic monitoring of calcineurin inhibitors, the long-term
outcome after transplantation (Tx) is still hampered by the side effects of these
drugs. The aim of the present study was to characterize nuclear factor of
activated T cells (NFAT)-regulated gene expression as a potential pharmacodynamic
biomarker for further individualization of tacrolimus (Tac) therapy. METHODS: In
29 renal allograft recipients, samples were drawn once pre-Tx, and before and 1.5
h after Tac dosing at approximately 1 week, 6 weeks and 1 year post-Tx. Tac
concentrations were measured by immunoassay, while the expression of genes
encoding NFAT-regulated cytokines [interleukin 2 (IL2), interferon gamma (IFNG),
colony stimulating factor 2 (CSF2)] and cytochrome P450 3A5 (CYP3A5) genotyping
were determined by real-time polymerase chain reaction. RESULTS: The cytokine
response after Tac dosing varied up to 46-fold between patients and changed
significantly with time post-engraftment. Tac concentrations 1.5 h postdose (C1.5
) >15 MUg l-1 were associated with strong cytokine inhibition and residual gene
expression (RGE) <=10%, while lower Tac C1.5 resulted in more variable responses
(RGE 2.5-68.7%). Patients with ongoing subclinical acute rejection (n = 5)
demonstrated limited cytokine inhibition (RGE 39.7-72.6%), while patients with
polyoma virus viraemia (n = 3) had relatively strong inhibition of cytokines (RGE
2.5-32.5%). By contrast, there was no association between Tac exposure and
rejection or viraemia. CONCLUSIONS: The findings of our study support the
potential of NFAT-regulated gene expression measurements as a pharmacodynamic
tool for additional monitoring of Tac therapy, especially in the context of
overimmunosuppression and viraemia.
PMID- 28686296
TI - A comparative study on basophil activation test, histamine release assay, and
passive sensitization histamine release assay in the diagnosis of peanut allergy.
AB - BACKGROUND: Allergy can be diagnosed using basophil tests. Several methods
measuring basophil activation are available. This study aimed at comparing
basophil activation test (BAT), histamine release assay (HR), and passive
sensitization histamine release assay (passive HR) in the diagnosis of peanut
allergy. METHODS: BAT, HR, and passive HR were performed on 11 peanut-allergic
and 14 nonallergic subjects. Blood was incubated with peanut extract or anti-IgE
and tests were performed as follows: BAT-CD63 upregulation was assessed by flow
cytometry; HR-released histamine was quantified by a glass fiber-based
fluorometric method; passive HR-IgE-stripped donor basophils were incubated with
participants' serum and histamine release was quantified as HR. RESULTS: CDsens,
a measure of basophil allergen sensitivity, was significantly higher for BAT
(80.1+/-17.4) compared to HR (23.4+/-10.31) and passive HR (11.1+/-2.0). BAT, HR,
and passive HR had a clinical sensitivity of 100%, 100%, and 82% and specificity
of 100%, 100%, and 100%, respectively, when excluding inconclusive results. BAT
identified 11 of 11 allergic patients, HR 10, and passive HR 9. Likewise, BAT
recognized 12 of 14 nonallergic subjects, HR 10, and passive HR 13. However, the
tests' diagnostic performances were not statistically different. Interestingly,
nonreleasers in HR but not in BAT had lower basophil count compared to releasers
(249 vs 630 counts/min). CONCLUSION: BAT displayed a significantly higher CDsens
compared to HR and passive HR. The basophil tests' diagnostic performances were
not significantly different. Still, BAT could diagnose subjects with low basophil
number in contrast to HR.
PMID- 28686297
TI - Multifaceted death receptor 3 signaling-promoting survival and triggering death.
AB - Death Receptor 3 (DR3) and its cognate ligand TL1A belong to the tumor necrosis
factor superfamily (TNFSF). This sophisticated network of receptor-ligand systems
controls innumerable biological processes. For many (if not all) TNFSF ligands
and receptors, a role in conditions such as inflammation, tissue development,
proliferation, and cell death has been firmly established. However, relatively
little is known about DR3 and TL1A. Here, we review novel aspects of DR3
signaling and DR3-associated signaling pathways before summarizing the function
of DR3 in the immune system. The emerging role of DR3 in disease will be
addressed before we finally critically discuss the potential therapeutic
exploitation of this receptor-ligand pair.
PMID- 28686298
TI - Predatory birds and ants partition caterpillar prey by body size and diet
breadth.
AB - The effects of predator assemblages on herbivores are predicted to depend
critically on predator-predator interactions and the extent to which predators
partition prey resources. The role of prey heterogeneity in generating such
multiple predator effects has received limited attention. Vertebrate and
arthropod insectivores constitute two co-dominant predatory taxa in many
ecosystems, and the emergent properties of their joint effects on insect
herbivores inform theory on multiple predator effects as well as biological
control of insect herbivores. Here we use a large-scale factorial manipulation to
assess the extent to which birds and ants engage in antagonistic predator
predator interactions and the consequences of heterogeneity in herbivore body
size and diet breadth (i.e. the diversity of host plants used) for prey
partitioning. We excluded birds and reduced ant density (by 60%) in the canopies
of eight northeastern USA deciduous tree species during two consecutive years and
measured the community composition and traits of lepidopteran larvae
(caterpillars). Birds did not affect ant density, implying limited intraguild
predation between these taxa in this system. Birds preyed selectively upon large
bodied caterpillars (reducing mean caterpillar length by 12%) and ants preyed
selectively upon small-bodied caterpillars (increasing mean caterpillar length by
6%). Birds and ants also partitioned caterpillar prey by diet breadth. Birds
reduced the frequency dietary generalist caterpillars by 24%, while ants had no
effect. In contrast, ants reduced the frequency of dietary specialists by 20%,
while birds had no effect, but these effects were non-additive; under bird
exclusion, ants had no detectable effect, while in the presence of birds, they
reduced the frequency of specialists by 40%. As a likely result of prey
partitioning by body size and diet breadth, the combined effects of birds and
ants on total caterpillar density were additive, with birds and ants reducing
caterpillar density by 44% and 20% respectively. These results show evidence for
the role of prey heterogeneity in driving functional complementarity among
predators and enhanced top-down control. Heterogeneity in herbivore body size and
diet breadth, as well as other prey traits, may represent key predictors of the
strength of top-down control from predator communities.
PMID- 28686299
TI - RANTES levels as a determinant of falciparum malaria severity or recovery.
AB - The study explored the role of differential RANTES concentrations, its receptor
CCR5 expression and resulting immunomodulation in the pathogenesis and/or
recovery from falciparum malaria. The study population included cases of
uncomplicated malaria (UC-M, N=128, enrolled on follow-up basis), severe malaria
(SM, N=25), and healthy controls (N=112). Serum RANTES and TNF-alpha levels were
evaluated by ELISA. Monocyte levels and activation profile were studied by flow
cytometry. Differential mRNA expression profile was studied by real-time PCR.
Blood parasite count was evaluated by registered pathologists. RANTES
concentration was significantly downregulated in SM cases compared to UC-M
(P=.046) and controls (P<.001). Expression of monocyte marker mCD14, activation
markers CCR5 and CD40, and downstream effector cytokine TNF-alpha was
significantly higher in malaria cases compared to controls, in SM cases compared
to UC-M. TNF-alpha expression correlated positively with CD40 and CCR5
expressions. Follow-up-based analysis showed that RANTES concentrations increased
on recovery compared to baseline in UC-M cases (P=.106) and inversely correlated
with malaria parasite load, mCD14, CCR5 and CD40, and TNF-alpha expressions.
These findings suggest an important association of RANTES concentrations in
Plasmodium falciparum malaria disease pathogenesis, as well as recovery, mediated
through differential modulation and regulated activation of monocytes and
cytokine TNF-alpha.
PMID- 28686300
TI - Statistical Learning and Spelling: Older Prephonological Spellers Produce More
Wordlike Spellings Than Younger Prephonological Spellers.
AB - The authors analyzed the spellings of 179 U.S. children (age = 3 years, 2 months
5 years, 6 months) who were prephonological spellers, in that they wrote using
letters that did not reflect the phonemes in the target items. Supporting the
idea that children use their statistical learning skills to learn about the outer
form of writing before they begin to spell phonologically, older prephonological
spellers showed more knowledge about English letter patterns than did younger
prephonological spellers. The written productions of older prephonological
spellers were rated by adults as more similar to English words than were the
productions of younger prephonological spellers. The older children s spellings
were also more wordlike on several objective measures, including length,
variability of letters within words, and digram frequency.
PMID- 28686301
TI - miRPursuit-a pipeline for automated analyses of small RNAs in model and nonmodel
plants.
AB - miRPursuit is a pipeline developed for running end-to-end analyses of high
throughput small RNA (sRNA) sequence data in model and nonmodel plants, from raw
data to identified and annotated conserved and novel sequences. It consists of a
series of UNIX shell scripts, which connect open-source sRNA analysis software.
The involved parameters can be combined with convenient workflow management by
users without advanced computational skills. miRPursuit presents several
advantages when compared to other tools, including the possibility of processing
several sRNA libraries in parallel, thus easily allowing a comparison of the
differences in sRNA read accumulation among sRNA libraries. We validate
miRPursuit by using datasets from a model plant and discuss its performance with
the analysis of sRNAs from non-model species.
PMID- 28686302
TI - Plasmalogen homeostasis - regulation of plasmalogen biosynthesis and its
physiological consequence in mammals.
AB - Plasmalogens, mostly ethanolamine-containing alkenyl ether phospholipids, are a
major subclass of glycerophospholipids. Plasmalogen synthesis is initiated in
peroxisomes and completed in the endoplasmic reticulum. The absence of
plasmalogens in several organs of peroxisome biogenesis-defective patients
suggests that the de novo synthesis of plasmalogens plays a pivotal role in its
homeostasis in tissues. Plasmalogen synthesis is regulated by modulating the
stability of fatty acyl-CoA reductase 1 on peroxisomal membranes, a rate-limiting
enzyme in plasmalogen synthesis, by sensing plasmalogens in the inner leaflet of
plasma membranes. Dysregulation of plasmalogen homeostasis impairs cholesterol
biosynthesis by altering the stability of squalene monooxygenase, a key enzyme in
cholesterol biosynthesis, implying physiological consequences of plasmalogen
homeostasis with respect to cholesterol metabolism in cells, as well as in organs
such as the liver.
PMID- 28686303
TI - Rural Veterans' dental utilization, Behavioral Risk Factor Surveillance Survey,
2014.
AB - INTRODUCTION: Rural residents are overrepresented in the military; however,
access to Veteran services is limited in rural areas. There is a need to identify
rural Veteran healthcare utilization. This study addresses that need and has two
purposes: a) to determine if there is an association between rural dwelling and
Veteran utilization of dental services; and b) to determine if there is an
association between rural dwelling and the oral health outcome of missing teeth.
METHODS: Data from the 2014 Behavioral Risk Factor Surveillance Survey were used
in this study. Chi square and logistic regression analyses were conducted.
FINDINGS: Rural Veterans were less likely to have a dental visit during the
previous year as compared with metropolitan Veterans in unadjusted analysis (Odds
ratio = 0.71, 95% Confidence Interval, 0.64, 0.77) and in adjusted analysis [0.87
(95% Confidence Interval, 0.78, 0.96)]. In cases in which all teeth were missing,
rural Veterans had an unadjusted odds ratio of 1.79 [95% Confidence Interval,
1.55, 2.08] and an adjusted odds ratio of 1.37 [95% Confidence Interval, 1.17,
1.62] as compared with metropolitan Veterans. DISCUSSION AND POLICY IMPLICATIONS:
The Veterans Health Administration develops policies for establishing centers for
care for Veterans. The policy development should take into consideration that
rural Veterans have not been as likely as urban Veterans to utilize dental
services and have poorer oral health outcomes.
PMID- 28686304
TI - Balanced N and C input recommendations for rain-fed maize production in northern
China based on N balances and grain yields.
AB - BACKGROUND: This study aimed to assess longer-term (1993-2009) effects of
combined applications of fertiliser, maize stover, and cattle manure on maize
yields, partial nitrogen (N) and carbon (C) balances, and water and N-use
efficiencies, to guide N and C input recommendations for rain-fed maize
production in northern China. RESULTS: The field trial, with three factors at
five levels and 12 treatments, was conducted at Shouyang Dryland-Farming
Experimental Station, Shanxi, China. Data analysis revealed higher N balances but
lower C balances significantly occurred in a dry year than in a wet year.
Positive N balances related to higher N inputs resulted in higher soil available
N, even downward to deep layers with increasing N inputs, while positive C
balances due to higher C inputs could be benefit to increase soil organic C.
Based on partial N balances and grain yields, N and C inputs at ranges of 100 kg
N ha-1 and 1.9-2.9 Mg C ha-1 could be recommended for target yields of 6.7-7.2 Mg
ha-1 in rain-fed maize production. CONCLUSION: The study suggests that N balances
close to neutral be given priority to improving N-use efficiency, and more
positive C balances also be important for sustaining target yields and soil
fertility levels. (c) 2017 Society of Chemical Industry.
PMID- 28686305
TI - Nanoscopic analysis of oxygen segregation at tilt boundaries in silicon ingots
using atom probe tomography combined with TEM and ab initio calculations.
AB - We have developed an analytical method to determine the segregation levels on the
same tilt boundaries (TBs) at the same nanoscopic location by a joint use of atom
probe tomography and scanning transmission electron microscopy, and discussed the
mechanism of oxygen segregation at TBs in silicon ingots in terms of bond
distortions around the TBs. The three-dimensional distribution of oxygen atoms
was determined at the typical small- and large-angle TBs by atom probe tomography
with a low impurity detection limit (0.01 at.% on a TB plane) simultaneously with
high spatial resolution (about 0.4 nm). The three-dimensional distribution was
correlated with the atomic stress around the TBs; the stress at large-angle TBs
was estimated by ab initio calculations based on atomic resolution scanning
transmission electron microscopy data and that at small-angle TBs were calculated
with the elastic theory based on dark-field transmission electron microscopy
data. Oxygen atoms would segregate at bond-centred sites under tensile stress
above about 2 GPa, so as to attain a more stable bonding network by reducing the
local stress. The number of oxygen atoms segregating in a unit TB area NGB (in
atoms nm-2 ) was determined to be proportional to both the number of the atomic
sites under tensile stress in a unit TB area nbc and the average concentration of
oxygen atoms around the TB [Oi ] (in at.%) with NGB ~ 50 nbc [Oi ].
PMID- 28686306
TI - Adele Ludin Boskey, PhD.
PMID- 28686307
TI - Characteristics of liver transplant candidates delisted following recompensation
and predictors of such delisting in alcohol-related liver disease: a case-control
study.
AB - Whether and when recovery beyond the need for transplant may occur in patients
listed for decompensation remains unclear. This study aimed to investigate the
characteristics of patients delisted following recompensation. Seventy-seven
patients who were listed between 2005 and 2015 for decompensation, but later
delisted following recompensation were included. Alcohol-related liver disease
(ALD) was the underlying etiology in the majority (n = 47, 61%). Listing
characteristics of these patients were compared with those of decompensated ALD
patients who either underwent deceased donor liver transplantation or died on the
waiting list. The model for end-stage liver disease (MELD) score <20 and serum
albumin >=32 g/l at listing were the only independent predictors of
recompensation/delisting in ALD. The probability of recompensation was 70% when
both factors were present at listing. Interestingly, about a tenth of
decompensated ALD patients who died on the waiting list (median duration on
waiting list 11 months) and a quarter of decompensated ALD patients who underwent
living donor liver transplantation (median duration on waiting list 2 months)
also had both factors at listing. In conclusion, ALD seems to be the most
favorable etiology for recompensation beyond the need for transplantation. Both
MELD and serum albumin at listing independently predict recompensation/delisting
in ALD. It seems advisable to implement a period of observation for ALD patients
with both favorable factors, before embarking on living donor liver
transplantation.
PMID- 28686308
TI - Total Syntheses of Pyroclavine, Festuclavine, Lysergol, and Isolysergol via a
Catalytic Asymmetric Nitro-Michael Reaction.
AB - A catalytic enantioselective construction of vicinal stereocenters is reported.
The reaction takes advantage of thiourea-catalyzed intramolecular nitronate
addition onto alpha,beta-unsaturated ester to afford exceptional levels of
enantioselectivity (up to 97 % ee) with moderate diastereoselectivity (up to
4:1). Using this method, a cross-conjugated ester was synthesized in few steps,
from which a 6-endo-trig cyclisation led to the formation of all required
functionalities for total syntheses of ergot alkaloids. The strategy not only
offers first total syntheses of ergot alkaloids, festuclavine (1 c), and
pyroclavine (1 e), and but also an efficient and general approach to other
congeners such as, lysergol (1 b), and isolysergol (1 d).
PMID- 28686309
TI - Absence of Calcitriol Causes Increased Lactational Bone Loss and Lower Milk
Calcium but Does Not Impair Post-lactation Bone Recovery in Cyp27b1 Null Mice.
AB - We hypothesized that adaptation to calcium supply demands of pregnancy and
lactation do not require calcitriol. Adult Cyp27b1 null mice lack calcitriol and
have hypocalcemia, hypophosphatemia, and rickets. We studied wild-type (WT) and
null sister pairs raised on a calcium-, phosphorus-, and lactose-enriched
"rescue" diet that prevents hypocalcemia and rickets. Bone mineral content (BMC)
increased >30% in pregnant nulls, declined 30% during lactation, and increased
30% by 4 weeks post-weaning. WT showed less marked changes. Micro-CT revealed
loss of trabecular bone and recovery in both genotypes. In lactating nulls,
femoral cortical thickness declined >30%, whereas endocortical perimeter
increased; both recovered to baseline after weaning; there were no such changes
in WT. Histomorphometry revealed a profound increase in osteoid surface and
thickness in lactating nulls, which recovered after weaning. By three-point bend
test, nulls had a >50% decline in ultimate load to failure that recovered after
weaning. Although nulls showed bone loss during lactation, their milk calcium
content was 30% lower compared with WT. Serum parathyroid hormone (PTH) was
markedly elevated in nulls at baseline, reduced substantially in pregnancy, but
increased again during lactation and remained high post-weaning. In summary,
pregnant Cyp27b1 nulls gained BMC with reduced secondary hyperparathyroidism,
implying increased intestinal calcium delivery. Lactating nulls lost more bone
mass and strength than WT, accompanied by increased osteoid, reduced milk
calcium, and worsened secondary hyperparathyroidism. This implies suboptimal
intestinal calcium absorption. Post-weaning, bone mass and strength recovered to
baseline, whereas BMC exceeded baseline by 40%. In conclusion, calcitriol
independent mechanisms regulate intestinal calcium absorption and trabecular bone
metabolism during pregnancy and post-weaning but not during lactation; calcitriol
may protect cortical bone during lactation. (c) 2017 American Society for Bone
and Mineral Research.
PMID- 28686310
TI - Neuromelanin magnetic resonance imaging of the substantia nigra in LRRK2-related
Parkinson's disease.
PMID- 28686311
TI - Anaphylaxis to horses and epinephrine use: Increasing awareness among pediatric
patients and families.
PMID- 28686312
TI - Flavonoid Composition of Tarocco (Citrus sinensis L. Osbeck) Clone "Lempso" and
Fast Antioxidant Activity Screening by DPPH-UHPLC-PDA-IT-TOF.
AB - INTRODUCTION: Clonal selection and hybridisation are valid strategies to obtain
fruits with enhanced sensorial and nutraceutical properties. Within Citrus
sinensis varieties, Tarocco clone "Lempso" is a typical product of the Calabria
region (Italy) characterised by its red pulp. This is the first report concerning
its accurate profiling. OBJECTIVE: To characterise in detail the flavonoid
composition of Lempso clone and to compare its antioxidant potential with other
Citrus varieties by a fast screening method. METHODOLOGY: Extracts were subjected
to solid phase extraction and the qualitative/quantitative profile was elucidated
through ultra-high performance liquid chromatography (UHPLC) coupled to
photodiode array (PDA) and ion trap time-of-flight (IT-TOF) mass spectrometry
detection, and compared to both Cleopatra mandarin (Citrus reticulata) and blood
orange (Citrus sinensis (L.) Osbeck) Sanguinello varieties. The antioxidant
activity was assessed by pre-column 2,2'-diphenyl-1-picrylhydrazyl (DPPH)
reaction coupled to UHPLC-PDA. RESULTS: Lempso is characterised by flavonoids
(17) and anthocyanins (8). Flavanones content (Hesperidin: 57.19 +/- 0.49,
Vicenin-2: 4.59 +/- 0.03, Narirutin: 5.78 +/- 0.13 mg/100 mL) was considerably
higher than Cleopatra and Sanguinello varieties. The developed DPPH-UHPLC-PDA
method provides information regarding the single contributions to antioxidant
activity, highlighting how Ferulic acid, Quercetin and Cyanidin derivatives
possess considerable radical scavenging activity (> 50%). The total antioxidant
activity was also evaluated and compared with positive controls, showing higher
scavenging activity than Cleopatra and Sanguinello (IC50 : 333.76 +/- 10.81
MUg/mL vs. 452.62 +/- 10.81 and 568.39 +/- 26.98 MUg/mL, respectively).
CONCLUSION: These data evidence the nutraceutical potential of Lempso variety,
which could be an ingredient for functional beverages. Copyright (c) 2017 John
Wiley & Sons, Ltd.
PMID- 28686313
TI - Rapid characterization of chemical constituents of Platycodon grandiflorum and
its adulterant Adenophora stricta by UPLC-QTOF-MS/MS.
AB - Platycodon grandiflorum (PG) is extensively used for treating cough, excessive
phlegm, sore throat, bronchitis and asthma, whereas Adenophora stricta (AS) is
commonly used to reduce phlegm, clear lung and tonify stomach. Due to similar
appearances, PG is sometimes adulterated with cheap AS so as to gain profits. And
this will inevitably result in different pharmacological property. In order to
further clarify the differences in the chemical composition of these two Chinese
herbs, the ultra-high performance liquid chromatography combined with quadrupole
time-of-flight tandem mass spectrometry coupled with UNIFI platform was used to
establish a reliable, simple, sensitive and rapid analytical method. Seventy-five
compounds, including triterpenoid saponins, organic acids, flavonoids, steroids,
phenols, etc., were identified from PG based on MSE data and retention time under
the optimized conditions. Meanwhile, 57 compounds including triterpenoid
saponins, organic acids, steroids, phenols, alkaloids, etc. were identified from
AS. Among all the identified compounds, there were only 14 common components
(mainly organic acids) existing in two herbs, and most of the other chemical
compositions are totally different between the two herbs. Based on the results,
AS cannot substitute for PG. In addition, PG adulterated with AS will lead a poor
efficacy in clinical application. In addition, the systematic comparison of
similarities and differences between two Chinese herbs will provide reliable
characterization profiles to clarify the pharmacological fundamental substances.
PMID- 28686314
TI - Several patient-reported outcome measures exist for children with atopic
eczema/dermatitis, but their validity is largely unknown.
PMID- 28686315
TI - Pentalogy of Cantrell in a monozygotic twin with a giant omphalocele firmly
attached to the amniotic membrane: Successful prenatal diagnosis and cesarean
delivery.
PMID- 28686316
TI - Is pre-transplant sensitization against angiotensin II type 1 receptor still a
risk factor of graft and patient outcome in kidney transplantation in the anti
HLA Luminex era? A retrospective study.
AB - We aimed to assess the correlation of anti-angiotensin II type 1 receptor
antibodies (anti-AT1R-Abs) before transplantation on a multicentric cohort of
kidney transplant recipients (2008-2012), under tacrolimus and mycophenolate
mofetil (MMF), screened by Luminex technology for anti-HLA immunization. Anti
AT1R antibody levels were measured by ELISA in pretransplantation sera of 940
kidney recipients from three French centers of the DIVAT cohort. Multivariable
Cox models estimated the association between pretransplant anti-angiotensin II
type 1 receptor antibodies and time to acute rejection episodes (ARE) or time to
graft failure. Within our cohort, 387 patients (41.2%) had pretransplant AT1R-Abs
higher than 10 U/ml and only 8% (72/970) greater than 17 U/ml. The cumulative
probability of clinically relevant (cr)-ARE was 22.5% at 1 year post
transplantation [95% CI (19.9-25.4%)]. The cumulative probability of graft
failure and patient death were 10.6% [95% CI (8.4-13.3%)] and 5.7% [95% CI (4.0
8.1%)] at 3 years post-transplantation, respectively. Multivariate Cox models
indicated that pretransplant anti-AT1R antibody levels higher than 10 U/ml were
not significantly independently associated with higher risks of acute rejection
episodes [HR = 1.04, 95% CI (0.80-1.35)] nor with risk of graft failure [HR =
0.86, 95% CI (0.56-1.33)]. Our study did not confirm an association between
pretransplant anti-AT1R antibody levels and kidney transplant outcomes.
PMID- 28686317
TI - Synaptotagmin-11 inhibits cytokine secretion and phagocytosis in microglia.
AB - Cytokine secretion and phagocytosis are key functions of activated microglia.
However, the molecular mechanisms underlying their regulation in microglia remain
largely unknown. Here, we report that synaptotagmin-11 (Syt11), a non-Ca2+
binding Syt implicated in Parkinson disease and schizophrenia, inhibits cytokine
secretion and phagocytosis in microglia. We found Syt11 expression in microglia
in brain slices and primary microglia. Interestingly, Syt11-knockdown (KD)
increased cytokine secretion and NO release in primary microglia both in the
absence and presence of lipopolysaccharide. NF-kappaB was activated in untreated
KD microglia together with enhanced synthesis of IL-6, TNF-alpha, IL-1beta, and
iNOS. When the release capacity was assessed by the ratio of extracellular to
intracellular levels, only the IL-6 and TNF-alpha secretion capacity was
increased in Syt11-KD cells, suggesting that Syt11 specifically regulates
conventional secretion. Consistently, Syt11 localized to the trans-Golgi network
and recycling endosomes. In addition, Syt11 was recruited to phagosomes and its
deficiency enhanced microglial phagocytosis. All the KD phenotypes were rescued
by expression of an shRNA-resistant Syt11, while overexpression of Syt11
suppressed cytokine secretion and phagocytosis. Importantly, Syt11 also inhibited
microglial phagocytosis of alpha-synuclein fibrils, supporting its association
with Parkinson disease. Taken together, we propose that Syt11 suppresses
microglial activation under both physiological and pathological conditions
through the inhibition of cytokine secretion and phagocytosis.
PMID- 28686318
TI - Pathophysiological heterogeneity in Parkinson's disease: Neurophysiological
insights from LRRK2 mutations.
PMID- 28686319
TI - Magnetic resonance thermometry of flowing blood.
AB - Blood temperature is a key determinant of tissue temperature and can be altered
under normal physiological states, such as exercise, in diseases such as stroke
or iatrogenically in therapies which modulate tissue temperature, such as
therapeutic hypothermia. Currently available methods for the measurement of
arterial and venous temperatures are invasive and, for small animal models, are
impractical. Here, we present a methodology for the measurement of intravascular
and tissue temperature by magnetic resonance imaging (MRI) using the lanthanide
agent TmDOTMA- (DOTMA, tetramethyl-1,4,7,10-tetraazacyclododecane-1,4,7,10
tetraacetic acid; Tm, thulium). The approach makes use of phase-sensitive imaging
measurements, combined with spectrally selective excitation, to monitor the
temperature-dependent shift in the resonance of proton nuclei associated with
water and with methyl groups of TmDOTMA- . Measurements were first made in a flow
phantom modelling diastolic blood flow in the mouse aorta or inferior vena cava
(IVC) and imaged using 7-T preclinical MRI with a custom-built surface coil.
Flowing and static fluid temperatures agreed to within 0.12 degrees C for these
experiments. Proof-of-concept experiments were also performed on three healthy
adult mice, demonstrating temperature measurements in the aorta, IVC and kidney
following a bolus injection of contrast agent. A small (0.7-1 degrees C), but
statistically significant, higher kidney temperature compared with the aorta (p =
0.002-0.007) and IVC (p = 0.003-0.03) was shown in all animals. These findings
demonstrate the feasibility of the technique for in vivo applications and
illustrate how the technique could be used to explore the relationship between
blood and tissue temperature for a wide range of applications.
PMID- 28686320
TI - The emerging science of precision medicine and pharmacogenomics for Parkinson's
disease.
AB - Current therapies for Parkinson's disease are problematic because they are
symptomatic and have adverse effects. New drugs have failed in clinical trials
because of inadequate efficacy. At the core of the problem is trying to make one
drug work for all Parkinson's disease patients, when we know this premise is
wrong because (1) Parkinson's disease is not a single disease, and (2) no two
individuals have the same biological makeup. Precision medicine is the goal to
strive for, but we are only at the beginning stages of building the
infrastructure for one of the most complex projects in the history of science,
and it will be a long time before Parkinson's disease reaps the benefits.
Pharmacogenomics, a cornerstone of precision medicine, has already proven
successful for many conditions and could also propel drug discovery and improve
treatment for Parkinson's disease. To make progress in the pharmacogenomics of
Parkinson's disease, we need to change course from small inconclusive candidate
gene studies to large-scale rigorously planned genome-wide studies that capture
the nuclear genome and the microbiome. Pharmacogenomic studies must use
homogenous subtypes of Parkinson's disease or apply the brute force of
statistical power to overcome heterogeneity, which will require large sample
sizes achievable only via internet-based methods and electronic databases. Large
scale pharmacogenomic studies, together with biomarker discovery efforts, will
yield the knowledge necessary to design clinical trials with precision to
alleviate confounding by disease heterogeneity and interindividual variability in
drug response, two of the major impediments to successful drug discovery and
effective treatment. (c) 2017 International Parkinson and Movement Disorder
Society.
PMID- 28686321
TI - Stratifying the potential local transmission of Zika in municipalities of
Antioquia, Colombia.
AB - OBJECTIVE: To stratify and understand the potential transmission processes of
Zika virus in Colombia, in order to effectively address the efforts on
surveillance and disease control. METHODS: We compare R0 of Zika for
municipalities based on data from the regional surveillance system of Antioquia,
Colombia. The basic reproduction number (R0 ) and its 95% confidence intervals
were estimated from an SIR model with implicit vector dynamics, in terms of
recovered individuals in each time unit, using an approximate solution. These
parameters were estimated fitting the solution of the model to the daily
cumulative frequency of each Zika case according to symptoms onset date relative
to the index case reported to the local surveillance system. RESULTS: R0 was
estimated for 20 municipalities with a median of 30 000 inhabitants, all located
less than 2200 m above sea level. The reported cases ranged from 17 to 347
between these municipalities within 4 months (January to April of 2016). The
results suggest that 15 municipalities had a high transmission potential (R0 >
1), whereas in five municipality transmissions were potentially not sustaining
(R0 < 1), although the upper bound of the confidence interval of the R0 for 3 of
these 5 was greater than one, indicating the possibility of an outbreak later on.
CONCLUSION: The study identified high-risk municipalities (R0 > 1) and provide a
technique to optimise surveillance and control of Zika. Health authorities should
promote the collection, analysis, modelling and sharing of anonymous data onto
individual cases to estimate R0 .
PMID- 28686322
TI - Characteristics of frequent emergency department users with type 2 diabetes
mellitus in Korea.
AB - AIMS/INTRODUCTION: Frequent emergency department (ED) visitors are medically
vulnerable individuals. We identified the characteristics of "frequent ED users"
among Korean patients with type 2 diabetes mellitus. MATERIALS AND METHODS: We
used the Health Insurance Review and Assessment Service National Patient Sample,
which is a nationally representative sample. Patients (n = 109,412) with type 2
diabetes mellitus as a primary or secondary diagnosis at one of their visits were
included. Individuals were classified into three groups according to the number
of ED visits: frequent (>=4 visits), occasional (<4 visits) and non-users of the
ED. The characteristics of the patients that distinguished frequent users from
the other groups were investigated. RESULTS: Frequent ED users were mainly men (P
< 0.001), with longer treatment duration (P < 0.001), more frequent comorbidities
(cardiovascular and chronic kidney disease) and primary diagnosis made by surgery
(P = 0.0028). They had higher mortality (P = 0.0085), longer hospitalization
duration (P < 0.001), higher costs per visit (P < 0.001) and more often required
medical protection (P < 0.001). These patients were treated more frequently with
sulfonylurea, insulin, meglitinide and alpha-glucosidase inhibitors (P < 0.05).
CONCLUSIONS: The present findings suggest that frequent users of the ED with type
2 diabetes mellitus have serious health conditions, a poor socioeconomic
situation and tend to take some medicines (sulfonylurea, etc.), which often are
associated with hypoglycemia. Attention should be given to therapy, and to
patients with renal and cardiovascular diseases to decrease the dependency of
these patients on the ED.
PMID- 28686323
TI - Exploration of Phytoconstituents from Mussaenda roxburghii and Studies of Their
Antibiofilm Effect.
AB - In the context of ethno botanical importance with no phytochemical
investigations, Mussaenda roxburghii have been investigated to explore it's
phytoconstituents and studies of their antibiofilm activity. Four compounds have
been isolated from the aerial parts of this plant and were characterized as
2alpha,3beta,19alpha,23-tetrahydroxyurs-12-en-28-oic acid (1), beta-sitosterol
glucoside (4), lupeol palmitate (5), and myoinositol (6). All these compounds
were tested for antibacterial and antibiofilm activity against Pseudomonas
aeruginosa. Compound 1 exhibited three times more antibiofilm activity with
minimum inhibitory concentration (MIC) at 0.74 mm compared to that of
streptomycin. Molecular docking studies exhibited a very high binding affinity of
1 with P. aeruginosa quorum sensing proteins and motility associated proteins
viz. LasR and PilB, PilY1, PilT, respectively. Compound 1 was also found to be
non-cytotoxic against sheep RBC and murine peritoneal macrophages at selected sub
MIC doses.
PMID- 28686324
TI - Demographics and co-occurring conditions in a clinic-based cohort with Down
syndrome in the United Arab Emirates.
AB - The majority of studies describing demographics and co-occurring conditions in
cohorts with Down syndrome come from regions outside of the Middle East, mainly
from Europe and North America. This paper describes demographics and co-occurring
conditions in a hospital-based cohort of individuals with Down syndrome living in
the Middle Eastern country of the United Arab Emirates (UAE). The first dedicated
Down syndrome clinic in the UAE was established in 2012 at Tawam Hospital in Al
Ain. This paper describes a clinic-based cohort of 221 participants over 4 years
from the Gulf Down Syndrome Registry, a new Down syndrome database and contact
registry created at Tawam Hospital. Key demographic findings include mean
maternal age of 37 years, among the highest described in the literature. Sixty
two percent of mothers are >35 years. Over 90% of mothers received post-natal
diagnosis of Down syndrome. High sex ratio, parental consanguinity, and large
family size also characterize the group. The spectrum of many co-occurring
conditions mirrors that of previously described populations, with some notable
differences. Cardiovascular malformations are well represented, however,
atrioventricular canal is not the most common. Genitourinary conditions are
common, as evidenced by 12% of males with hypospadias and 15% with undescended
testes. Glucose-6-phosphate dehydrogenase deficiency, alpha thalassemia trait,
hypovitaminosis D, and dental caries are common in our cohort. This study
describes a large hospital-based group with Down syndrome presenting to a new
dedicated Down syndrome clinic in the UAE, highlighting unique demographic and co
occurring conditions found in that population.
PMID- 28686325
TI - RNF213 variants in a child with PHACE syndrome and moyamoya vasculopathy.
AB - Segmental infantile hemangiomas (IH) can be associated with congenital anomalies
in a regional distribution. PHACE refers to large cervicofacial segmental IH in
association with congenital anomalies of the aortic arch and medium-sized
arteries of the head and neck, as well as structural anomalies of the posterior
fossa and eye. A subset of PHACE patients have arterial anomalies that progress
to moyamoya vasculopathy (MMV). MMV is defined as stenosis of the supraclinoid
segment of the internal carotid arteries and/or their major branches, with
subsequent development of a compensatory collateral vessel network. We describe a
patient with MMV and segmental IH on the back and lower body who meets diagnostic
criteria for PHACE based on a posterior segment eye anomaly and cerebral arterial
anomalies. Whole exome sequencing demonstrated two inherited heterozygous
variants in RNF213. Variants in RNF213 are associated with increased
susceptibility to MMV. Our findings suggest that RNF213 variants may play a role
in the development of MMV in patients with hemangioma syndromes associated with
congenital cerebral arterial anomalies.
PMID- 28686326
TI - Single-nucleotide polymorphisms in genes related to the hypothalamic-pituitary
adrenal axis as risk factors for posttraumatic stress disorder.
AB - Posttraumatic stress disorder (PTSD) is a common psychiatric disorder. The
etiology of PTSD is multifactorial, depending on many environmental and genetic
risk factors, and the exposure to life or physical integrity-threatening events.
Several studies have shown significant correlations of many neurobiological
findings with PTSD. Hypothalamic-pituitary-adrenal (HPA) axis dysfunction is
strongly correlated with this disorder. One hypothesis is that HPA axis
dysfunction may precede the traumatic event, suggesting that genes expressed in
the HPA axis may be involved in the development of PTSD. This article reviews
molecular genetic studies related to PTSD collected through a literature search
performed in PubMed, MEDLINE, ScienceDirect, and Scientific Electronic Library
Online (SciELO). The results of these studies suggest that several polymorphisms
in the HPA axis genes, including FKBP5, NR3C1, CRHR1, and CRHR2, may be risk
factors for PTSD development or may be associated with the severity of PTSD
symptoms.
PMID- 28686327
TI - HLA-A*02:687, a novel allele identified by sequence-based typing in cord blood
from a Korean woman.
AB - A*02:687 showed one nucleotide difference with A*02:01:01:01 resulting in an
amino acid change.
PMID- 28686328
TI - Genetically contextual effects of smoking on genome wide DNA methylation.
AB - Smoking is the leading cause of death in the United States. It exerts its effects
by increasing susceptibility to a variety of complex disorders among those who
smoke, and if pregnant, to their unborn children. In prior efforts to understand
the epigenetic mechanisms through which this increased vulnerability is conveyed,
a number of investigators have conducted genome wide methylation analyses.
Unfortunately, secondary to methodological limitations, these studies were unable
to examine methylation in gene regions with significant amounts of genetic
variation. Using genome wide genetic and epigenetic data from the Framingham
Heart Study, we re-examined the relationship of smoking status to genome wide
methylation status. When only methylation status is considered, smoking was
significantly associated with differential methylation in 310 genes that map to a
variety of biological process and cellular differentiation pathways. However,
when SNP effects on the magnitude of smoking associated methylation changes are
also considered, cis and trans-interaction effects were noted at a total of 266
and 4353 genes with no marked enrichment for any biological pathways.
Furthermore, the SNP variation participating in the significant interaction
effects is enriched for loci previously associated with complex medical
illnesses. The enlarged scope of the methylome shown to be affected by smoking
may better explicate the mediational pathways linking smoking with a myriad of
smoking related complex syndromes. Additionally, these results strongly suggest
that combined epigenetic and genetic data analyses may be critical for a more
complete understanding of the relationship between environmental variables, such
as smoking, and pathophysiological outcomes.
PMID- 28686329
TI - Juvenile-onset generalized lipodystrophy due to a novel heterozygous missense
LMNA mutation affecting lamin C.
AB - The LMNA gene contains 12 exons and encodes lamins A and C by alternative
splicing within exon 10. While mutations in lamin A specific residues cause
several diseases including lipodystrophy, progeria, muscular dystrophy,
neuropathy, and cardiomyopathy, only three families with mutations in lamin C
specific residues are reported with cardiomyopathy, neuropathy, and muscular
dystrophy so far. We now report two brothers with juvenile-onset generalized
lipodystrophy due to a lamin C-specific mutation. The proband, a 23-year-old
Caucasian male was reported to have generalized lipodystrophy at 3 weeks of age,
developed diabetes, hypertriglyceridemia, hypertension and liver problems and
died with complications of cirrhosis, and kidney failure. His younger brother, a
37-year-old Caucasian male developed generalized lipodystrophy around 2 years of
age and was diagnosed with diabetes, hypertriglyceridemia, fatty liver, and
hypertension at 36 years of age. Their father also died of end stage renal
disease at age 52 years. Exome sequencing of the proband revealed an extremely
rare missense heterozygous variant c.1711_1712CG>TC; p.(Arg571Ser) in LMNA which
was confirmed by Sanger sequencing in both the patients. Interestingly, the
mutation had no effect on mRNA splicing or relative expression of lamin A or C
mRNA and protein in the lymphoblasts. Our observations suggest that mutant lamin
C disrupts its interaction with other cellular proteins resulting in generalized
lipodystrophy due to defective development and maintenance of adipose tissue.
PMID- 28686330
TI - GSTP1 c.313A>G, XPD c.934G>A, XPF c.2505T>C and CASP9 c.-1339A>G Polymorphisms
and Severity of Vomiting in Head and Neck Cancer Patients treated with Cisplatin
Chemoradiation.
AB - Cisplatin (CDDP) chemotherapy associated with radiation (RT) has been used in
advanced head and neck squamous cell carcinoma (HNSCC) patients, and vomiting is
a common side effect during treatment. This prospective study aimed to identify
the roles of GSTM1 and GSTT1 (presents or nulls), GSTP1 c.313A>G, XPC c.2815A>C,
XPD c.934G>A and c.2251A>C, XPF c.2505T>C, ERCC1 c.354C>T, MLH1 c.-93G>A, MSH2
c.211 + 9C>G, MSH3 c.3133G>A, EXO1 c.1765G>A, TP53 c.215G>C, CASP3 c.-1191A>G and
c.-1168G>T, CASP9 c.-1339A>G, CASP8 c.-937_-932delAGTAAG, FAS c.-1378G>A and c.
671A>G, and FASL c.-157-687C>T single nucleotide polymorphisms, involved in CDDP
metabolism, in vomiting severity in 88 HNSCC patients treated with CDDP and RT.
Ondansetron and dexamethasone were administered as anti-emetic therapy. Patients
with GSTP1 c.313AG or GG genotype alone and combined with XPD c.934GA or AA, XPF
c.2505TC or CC, and CASP9 c.-1339AG or GG genotypes had 4.28, 5.00, 5.45 and 5.38
more chances of presenting moderate/severe vomiting than patients with others
genotypes. Our data suggest, for the first time, that inherited abnormality in
apoptosis pathway alone or combined with inherited abnormalities in DNA repair
pathway, is capable of modulating emesis in HNSCC patients under CDDP
chemoradiation and may be used for selecting patients who should receive pre
emptive anti-emetic therapy.
PMID- 28686331
TI - Neural tube defects in Waardenburg syndrome: A case report and review of the
literature.
AB - Waardenburg syndrome type 1 (WS1) is an autosomal dominant genetic condition
characterized by sensorineural deafness and pigment abnormalities, and is caused
by variants in the PAX3 homeodomain. PAX3 variants have been associated with
severe neural tube defects in mice and humans, but the frequency and clinical
manifestations of this symptom remain largely unexplored in humans. Consequently,
the role of PAX3 in human neural tube formation remains a study of interest, for
clinical as well as research purposes. Though the association between spina
bifida and WS1 is now well-documented, no study has attempted to characterize the
range of spina bifida phenotypes seen in WS. Spina bifida encompasses several
diagnoses with a wide scope of clinical severity, ranging from spina bifida
occulta to myelomeningocele. We present a patient with Waardenburg syndrome type
1 caused by a novel missense variant in PAX3, presenting with myelomeningocele,
Arnold-Chiari malformation, and hydrocephalus at birth. Additionally, we review
32 total cases of neural tube defects associated with WS. Including this report,
there have been 15 published cases of myelomeningocele, 10 cases of unspecified
spina bifida, 3 cases of sacral dimples, 0 cases of meningocele, and 4 cases of
miscellaneous other neural tube defects. Though the true frequency of each
phenotype cannot be determined from this collection of cases, these results
demonstrate that Waardenburg syndrome type 1 carries a notable risk of severe
neural tube defects, which has implications in prenatal and genetic counseling.
PMID- 28686332
TI - Investigation of poly[oligo(ethylene glycol)diacrylates] as potential stationary
phases in GC.
AB - Poly[oligo(ethylene glycol)diacrylate]s were investigated as potential candidates
for application as stationary phases in capillary gas chromatography. Depending
on the molar mass of the monomer, up to three different phase transitions were
observed in calorimetric scans of the polymers. Two transitions have been
identified as the glass transition and melting of crystallites while the nature
of the third effect remains unknown. The new stationary phases demonstrate a good
separating ability and selectivity in the viscous-elastic state, i.e. at
temperatures above the glass transition and melting points. The new polymeric
stationary phases possess selectivity similar to conventional PEG columns but
provide better thermal stability than conventional PEG stationary phases.
PMID- 28686333
TI - eHealth provides a novel opportunity to exploit the advantages of the Nordic
countries in psychiatric genetic research, building on the public health care
system, biobanks, and registries.
AB - Nordic countries have played an important role in the recent progress in
psychiatric genetics, both with large well-characterized samples and expertise.
The Nordic countries have research advantages due to the organization of their
societies, including system of personal identifiers, national health registries
with information about diseases, treatment and prescriptions, and a public health
system with geographical catchment areas. For psychiatric genetic research, the
large biobanks and population surveys are a unique added value. Further, the
population is motivated to participate in research, and there is a trust in the
institutions of the society. These factors have been important for Nordic
contributions to biomedical research, and particularly psychiatric genetics. In
the era of eHealth, the situation seems even more advantageous for Nordic
countries. The system with public health care makes it easy to implement national
measures, and most of the Nordic health care sector is already based on
electronic information. The potential advantages regarding informed consent,
large scale recruitment and follow-up, and longitudinal cohort studies are
tremendous. New precision medicine approaches can be tested within the health
care system, with an integrated approach, using large hospitals or regions of the
country as a test beds. However, data protection and legal framework have to be
clarified. In order to succeed, it is important to keep the people's trust, and
maintain the high ethical standards and systems for secure data management. Then
the full potential of the Nordic countries can be leveraged in the new era of
precision medicine including psychiatric genetics.
PMID- 28686334
TI - Catalytic Hydrodeoxygenation of High Carbon Furylmethanes to Renewable Jet-fuel
Ranged Alkanes over a Rhenium-Modified Iridium Catalyst.
AB - Renewable jet-fuel-range alkanes are synthesized by hydrodeoxygenation of
lignocellulose-derived high-carbon furylmethanes over ReOx -modified Ir/SiO2
catalysts under mild reaction conditions. Ir-ReOx /SiO2 with a Re/Ir molar ratio
of 2:1 exhibits the best performance, achieving a combined alkanes yield of 82-99
% from C12 -C15 furylmethanes. The catalyst can be regenerated in three
consecutive cycles with only about 12 % loss in the combined alkanes yield.
Mechanistically, the furan moieties of furylmethanes undergo simultaneous ring
saturation and ring opening to form a mixture of complex oxygenates consisting of
saturated furan rings, mono-keto groups, and mono-hydroxy groups. Then, these
oxygenates undergo a cascade of hydrogenolysis reactions to alkanes. The high
activity of Ir-ReOx /SiO2 arises from a synergy between Ir and ReOx , whereby the
acidic sites of partially reduced ReOx activate the C-O bonds of the saturated
furans and alcoholic groups while the Ir sites are responsible for hydrogenation
with H2 .
PMID- 28686335
TI - Infection and apoptosis associated with inflammation in periodontitis: An
immunohistologic study.
AB - OBJECTIVE: Evidence of increased apoptosis is observed in periodontitis and may
be associated with destruction of the periodontal tissue caused by the increased
cell death, with the release of danger signals and subsequent stimulation of the
proinflammatory processes. However, the exact mechanisms associated with these
processes remain unclear. This study aimed to investigate the presence of the
periodontal pathogen Treponema denticola, apoptosis, high mobility group box 1 as
a damage-associated molecular pattern, and several inflammatory markers in
periodontitis and gingivitis subjects. MATERIALS AND METHODS: Soft tissue
specimens from gingival tissues of periodontitis and gingivitis patients were
used for immunohistochemical and immunofluorescence staining of T. denticola
chymotrypsin-like proteinase (CTLP), apoptosis markers, high mobility group box
1, Toll-like receptor 4, inflammatory cell markers, and proinflammatory
cytokines. RESULTS: Treponema denticola was detected in all periodontitis
affected tissues. This was associated with a significant increase in the number
of apoptotic cells, including macrophages, alterations in the expression of high
mobility group box 1 and its receptor, and increased levels of proinflammatory
cytokines compared with gingivitis. CONCLUSIONS: In summary, the presence of T.
denticola (especially its CTLP), apoptosis, high mobility group box 1, and
inflammatory markers suggests their potential involvement in the pathogenesis of
periodontitis.
PMID- 28686336
TI - Axially Symmetric U-O-Ln- and U-O-U-Containing Molecules from the Control of
Uranyl Reduction with Simple f-Block Halides.
AB - The reduction of UVI uranyl halides or amides with simple LnII or UIII salts
forms highly symmetric, linear, oxo-bridged trinuclear UV /LnIII /UV , LnIII /UIV
/LnIII , and UIV /UIV /UIV complexes or linear LnIII /UV polymers depending on
the stoichiometry and solvent. The reactions can be tuned to give the products of
one- or two-electron uranyl reduction. The reactivity and magnetism of these
compounds are discussed in the context of using a series of strongly oxo-coupled
homo- and heterometallic poly(f-block) chains to better understand fundamental
electronic structure in the f-block.
PMID- 28686337
TI - Blake's pouch cyst in 13q deletion syndrome: Posterior fossa malformations may
occur due to disruption of multiple genes.
PMID- 28686338
TI - Early versus late-applied constraint-induced movement therapy: A multisite,
randomized controlled trial with a 12-month follow-up.
AB - BACKGROUND AND PURPOSE: A direct comparison between the effects of constraint
induced movement therapy (CIMT) applied early after stroke and that of CIMT
applied in the chronic phase has not been conducted. This study aimed to compare
the long-term effects of CIMT applied 6 months after stroke with the results of
CIMT applied within 28 days post-stroke. METHODS: This study was a single
blinded, multicentre, randomized controlled trial with a crossover design. Forty
seven patients received CIMT either early (within 28 days) or 6 months after
stroke. Both groups received standard rehabilitation and were tested at 5 time
points. The primary outcome measure was Wolf Motor Function Test (WMFT); the
secondary measures were Nine-Hole Peg Test (NHPT), the Fugl-Meyer Assessment
(FMA) of the upper extremity, Stroke Impact Scale, and Modified Rankin Scale
(MRS). RESULTS: Compared with baseline data, both groups showed significant
improvements in the primary and secondary outcome measures after 12 months. No
significant differences between the 2 treatment groups were found before and
after the delayed intervention group received CIMT at 6 months and during the 12
month follow-up. Both groups recovered considerably and showed only minor
impairment (median FMA score of 64) after 6 months. The early intervention group
showed an initially faster recovery curve of WMFT, NHPT, and MRS scores.
DISCUSSION: In contrast to most CIMT studies, our study could not find an effect
of CIMT applied 6 months after stroke. Our results indicate that commencing CIMT
early is as good as delayed intervention in the long term, specifically in this
group of patients who might have reached a ceiling effect during the first 6
months after stroke. Nevertheless, the early CIMT intervention group showed a
faster recovery curve than the delayed intervention group, which can be a
clinically important finding for patients in the acute phase.
PMID- 28686342
TI - Asymptomatic Upper Lip Swelling in an 8-Year-Old Boy.
PMID- 28686343
TI - Patient Perspectives: What is Tinea?
PMID- 28686341
TI - Three regulators of G protein signaling differentially affect mating, morphology
and virulence in the smut fungus Ustilago maydis.
AB - Regulators of G protein signaling (RGS) proteins modulate heterotrimeric G
protein signaling negatively. To broaden an understanding of the roles of RGS
proteins in fungal pathogens, we functionally characterized the three RGS protein
encoding genes (rgs1, rgs2 and rgs3) in the phytopathogenic fungus Ustilago
maydis. It was found that RGS proteins played distinct roles in the regulation of
development and virulence. rgs1 had a minor role in virulence when deleted in a
solopathogenic strain. In crosses, rgs1 was dispensable for mating and
filamentation, but was required for teliospore production. Haploid rgs2 mutants
were affected in cell morphology, growth, mating and were unable to cause disease
symptoms in crosses. However, virulence was unaffected when rgs2 was deleted in a
solopathogenic strain, suggesting an exclusive involvement in pre-fusion events.
These rgs2 phenotypes are likely connected to elevated intracellular cAMP levels.
rgs3 mutants were severely attenuated in mating, in their response to pheromone,
virulence and formation of mature teliospores. The mating defect could be traced
back to reduced expression of the transcription factor rop1. It was speculated
that the distinct roles of the three U. maydis RGS proteins were achieved by
direct modulation of the Galpha subunit-activated signaling pathways as well as
through Galpha-independent functions.
PMID- 28686345
TI - Multiple Milia as an Isolated Skin Manifestation of Dominant Dystrophic
Epidermolysis Bullosa: Evidence of Phenotypic Variability.
PMID- 28686344
TI - Persistent Vulval Symptoms in a 16-Year-Old Girl.
PMID- 28686346
TI - Recurrent Erythematous Papules and Nodules on the Trunk and Extremities of a 3
Year-Old Girl.
PMID- 28686347
TI - EPO modified MSCs can inhibit asthmatic airway remodeling in an animal model.
AB - There was no effective measures can be obtained at present to reverse or prevent
airway remodeling. We investigated the therapeutic effect of Erythropoietin (EPO)
gene modified mesenchymal stem cells (MSCs) on asthmatic airway remodeling and
the possible underlied molecular mechanisms. EPO gene was transfected into MSCs
via lentivirus vector. The transfected cells (EPO-MSCs) were identified by flow
cytometry and the EPO secreting function was detected by PCR and Western blot.
MSCs or EPO-MSCs were administrated to albumin (OVA)-induced chronic asthmatic
mouse model via tail veins. The asthmatic phenotype was analyzed. Number of cells
in bronchoalveolar lavage fluid (BALF) was counted using a hemocytometer.
Histological findings of airways were evaluated by microscopic examination. The
concentrations of interleukin 4(IL-4), interleukin 5(IL-5), and interleukin 13(IL
13) in lung homogenate were determined by ELISA. The activation state of
transforming growth factor-beta 1 (TGF-beta1), Transforming growth factor beta
activated kinase 1 (TAK1), and p38 Mitogen Activated Protein Kinase (p38MAPK)
signaling was detected by Real-Time PCR and Western blotting. EPO-MSCs were
successfully constructed. EPO-MSCs showed a more potently suppressive effect on
local asthmatic airway inflammation and the level of IL-4, IL-5, and IL-13 in
lung tissue than MSCs. Moreover, the numbers of goblet cells, the thicknesses of
smooth muscle layer, collagen density, percentage of proliferating cell nuclear
antigen positive (PCNA+ ) mesenchymal cells, and von Willebrand factor
positive(vWF+ ) vessels were also significantly inhibited by EPO-MSCs.
Furthermore, EPO-MSCs could downregulate the expression of TGF-beta1, TAK1, and
p38MAPK in lung tissue both in mRNA level and in protein level. EPO gene modified
MSCs may more efficiently attenuate asthmatic airway remodeling, which maybe
related with the downregulation of TGF-beta1-TAK1-p38MAPK pathway activity.
PMID- 28686348
TI - Synthesis and Applications of Cyclohexenyl Halides Obtained by a Cationic
Carbocyclisation Reaction.
AB - The synthesis of cyclic alkenyl halides (mainly fluorides, chlorides and
bromides) from alkynol or enyne derivatives by an acid-mediated cationic
cyclisation reaction is disclosed. This high-yielding, scalable and technically
simple method complements and challenges conventional methodologies. This study
includes the development of biomimetic cationic cyclisation reactions of
polyenyne derivatives to give interesting halogen-containing polycyclic
compounds. The application of this reaction in the key step of the synthesis of
two terpenes, namely austrodoral and pallescensin A, and the potent odorant 9-epi
Ambrox demonstrates the potential of the reaction for natural product synthesis.
PMID- 28686349
TI - The role of vitamin D on circulating memory T cells in children: The Generation R
study.
AB - BACKGROUND: Previous studies have demonstrated that vitamin D affects T-cell
function and maturation via the vitamin D receptor. However, no studies in
children have been performed on this topic. Because most of the T-cell memory is
formed in the first 5 years of life, we aimed to determine the association
between serum 25-hydroxyvitamin D (25(OH)D) levels and numbers of circulatory
naive, central memory (Tcm), and effector memory (Tem) T lymphocytes in a large
population of healthy children. METHODS: Among 3189 children participating in a
population-based prospective cohort, we measured 25(OH)D levels and performed
detailed immunophenotyping of naive and memory T lymphocytes at a median age of
6.0 years (95% range 5.7-7.9). Detailed lymphocyte subsets were available in 986
children. Multivariable linear regression analyses were performed to determine
the association between 25(OH)D and the maturation of T lymphocytes in children
adjusted for cord blood 25(OH)D levels, herpes seropositivity, sociodemographic
and lifestyle confounders. Furthermore, multivariable logistic regression
analyses were performed to determine associations between 25(OH)D and childhood
infections. RESULTS: Higher 25(OH)D levels were associated with higher numbers of
Tem lymphocytes. Every 10 nmol/L higher 25(OH)D was associated with 2.20% (95% CI
0.54-3.89; P=.009) higher CD4TemRA, 1.50% (95% CI 0.38-2.62; P=.008) higher
CD4TemRO, and 1.82% (95% CI 0.11-3.56; P=.037) higher CD8TemRA cell numbers.
Generally, stronger associations were observed among boys. 25(OH)D levels were
not significantly associated with naive, Tcm cell numbers, herpes seropositivity,
or URTIs. CONCLUSIONS: Our results suggest that vitamin D enhances cellular
immunity in young children.
PMID- 28686350
TI - A Comparative Study of Basic, Amphoteric, and Acidic Catalysts in the Oxidative
Coupling of Methanol and Ethanol for Acrolein Production.
AB - The impact of acid/base properties (determined by adsorption microcalorimetry) of
various catalysts on the cross-aldolization of acetaldehyde and formaldehyde
leading to acrolein was methodically studied in oxidizing conditions starting
from a mixture of methanol and ethanol. The aldol condensation and further
dehydration to acrolein were carried out on catalysts presenting various
acid/base properties (MgO, Mg-Al oxides, Mg/SiO2 , NbP, and heteropolyanions on
silica, HPA/SiO2 ). Thermodynamic calculations revealed that cross-aldolization
is always favored compared with self-aldolization of acetaldehyde, which leads to
crotonaldehyde formation. The presence of strong basic sites is shown to be
necessary, but a too high amount drastically increases COx production. On strong
acid sites, production of acrolein and carbon oxides (COx ) does not increase
with temperature. The optimal catalyst for this process should be amphoteric with
a balanced acid/base cooperation of medium strength sites and a small amount
(<100 MUmol g-1 ) of very strong basic sites (Qdiff >150 kJ mol-1 ).
PMID- 28686351
TI - The Molting Biomarker Molecule Exists as 2-Acetamido-2-deoxy-gluconic Acid in
Urine of Blue Crabs and Helmet Crabs.
AB - N-Acetyl-d-glucosamino-1,5-lactone 1 has been reported as a candidate component
of the sex pheromone mixture of female blue crabs, Callinectes sapidus, since it
is present in the urine of reproductive females and males detect it.
Theoretically, 1 can convert to a 1,4-lactone isomer 2 or to the corresponding
carboxylic acid, 2-acetamido-2-deoxygluconic acid 3 by hydrolysis in aqueous
solution. In this study, we examined the biologically relevant state of
equilibrium mixture of 1, 2, and 3 in crab urine using ESI-MS and NMR analyses.
The ESI-MS analysis showed that the dominant form of solubilized synthetic 1 is
lactone 1 and/or 2, immediately after solubilization in deuterated water,
seawater, and phosphate buffer and gradually changing to carboxylic acid 3 which
becomes most predominant in phosphate buffer. The NMR analysis showed that
synthetic 1 converts to other forms in deuterated water and seawater, and reaches
an equilibrium mixture of at least three forms within 24 h. In contrast, 1
converts to a single state of another form in deuterated water with 35 mm
phosphate buffer pH 7.6 within 24 h, which is identical to the state in urine
with or without phosphate buffer. Thus, we conclude that the molting biomarker
sensed by male crabs is 3.
PMID- 28686352
TI - Ratio of visceral-to-subcutaneous fat area predicts cardiovascular events in
patients with type 2 diabetes.
AB - AIMS/INTRODUCTION: To investigate whether the ratio of visceral fat area (VFA) to
subcutaneous fat area (SFA; V/S ratio) could be predictive of cardiovascular
disease (CVD) as compared with VFA or SFA in patients with diabetes. MATERIALS
AND METHODS: A total of 682 patients with type 2 diabetes (mean age 64 +/- 13
years; 41% women) were enrolled. VFA (cm2 ) and SFA (cm2 ) were assessed by a
dual bioelectrical impedance analyzer. The patients were divided into four groups
according to the quartiles of the V/S ratio. The study end-point was the first
occurrence or recurrence of CVD. RESULTS: Over a median follow up of 2.5 years,
21 patients reached the end-point. The number of patients who reached the end
point was increased along with the increasing of the V/S ratio quartiles. The V/S
ratio was significantly associated with incident or recurrent CVD (hazard ratio
[HR] 1.82, 95% CI: 1.09-3.04, P = 0.021) after adjusting for estimated glomerular
filtration rate (HR 0.98, 95% CI: 0.96-1.00), brain-type natriuretic peptide (HR
1.00, 95% CI: 1.00-1.01), use of antiplatelet agents (HR 4.26, 95% CI: 1.63
11.13), coefficient of variation of R-R intervals (HR 0.85, 95% CI: 0.69-1.10)
and glycated hemoglobin (HR 1.37, 95% CI: 1.05-1.79). The addition of the V/S
ratio to age, estimated glomerular filtration rate, brain-type natriuretic
peptide, antiplatelet agents and glycated hemoglobin significantly improved
classification performance for CVD using net reclassification improvement (0.60,
95% CI: 0.21-1.00) and the integrated discrimination improvement (0.02, 95% CI:
0.00-0.05). CONCLUSIONS: The V/S ratio measured by dual bioelectrical impedance
analyzer is an independent predictor of CVD in patients with type 2 diabetes.
PMID- 28686354
TI - Improvement in respiratory muscle O2 delivery is associated with less dyspnoea
during exercise in COPD.
PMID- 28686353
TI - National-scale precision medicine for psychiatric disorders in Sweden.
AB - Since psychiatric disorders have genetic architectures dominated by common
variants of small effects, successful elucidation in psychiatric genetics
necessitates large sample sizes. Collaboration and unconventional ascertainment
methods are required to fulfill this need. Electronic health records have been
increasingly seen as holding great potential for research, although they often
pose substantial technical, legal and ethical challenges. Universal health care
and national-scale registers with comprehensive medical, developmental,
demographic, and geographic information make the Nordic countries ideal for
psychiatric genetic epidemiology. The Genomic Aggregation Project in Sweden is
gathering genetic data from subjects with and without complex genetic diseases in
a single location for standardized processing and use in a wide variety of
scientific investigations. Thirty groups with >160 K genotyped samples have
joined GAPS. Although GAPS is general across medicine, many psychiatric disorders
are represented within GAPS, and initial studies will focus on major depressive
disorder. Through in-depth genetic investigations, the genes and pathways that
will be identified can be leveraged for predictive and drug-development purposes.
Sweden offers exceptional possibilities for psychiatric genetics, and GAPS aims
to harness the wealth of available information for research to improve human
health.
PMID- 28686355
TI - Survey of the genomic landscape surrounding the 5-enolpyruvylshikimate-3
phosphate synthase (EPSPS) gene in glyphosate-resistant Amaranthus palmeri from
geographically distant populations in the USA.
AB - BACKGROUND: Glyphosate resistance in Amaranthus palmeri, one of the most
prevalent herbicide-resistant weeds in the USA, is attributable to amplification
and increased expression of the gene encoding the target site of glyphosate, 5
enolpyruvylshikimate-3-phosphate synthase (EPSPS). The EPSPS gene and the
surrounding 287 kilobases (kb) of amplified sequence are unique to glyphosate
resistant plants and termed the EPSPS cassette. It has only been sequenced in one
A. palmeri population from Mississippi. This research compares EPSPS cassettes in
seven resistant and five sensitive populations from geographically distant
locations within the USA, including Mississippi, Arizona, Kansas, Maryland,
Delaware and Georgia. RESULTS: Polymerase chain reaction (PCR) products from 40
primer pairs specific to the cassette were similar in size and sequence in
resistant populations. Several primer pairs failed to generate PCR products in
sensitive populations. Regions of the cassette sequenced in the resistant
populations were found to be nearly identical to those from Mississippi. Gene
expression analysis showed that both EPSPS and another gene in the cassette, a
reverse transcriptase, were elevated in all resistant populations tested relative
to the sensitive populations. CONCLUSION: EPSPS cassettes from distant resistant
populations were nearly homologous. Considering the complexity of the cassette,
and the degree of similarity among some cassette sequences, the results are
consistent with the hypothesis that glyphosate resistance probably evolved once
and then rapidly spread across the USA. (c) 2017 Society of Chemical Industry.
PMID- 28686356
TI - Relaxing Responses to Hydrogen Peroxide and Nitric Oxide in Human Pericardial
Resistance Arteries Stimulated with Endothelin-1.
AB - In human pericardial resistance arteries, effects of the endothelium-dependent
vasodilator bradykinin are mediated by NO during contraction induced by K+ or the
TxA2 analogue U46619 and by H2 O2 during contraction by endothelin-1 (ET-1),
respectively. We tested the hypotheses that ET-1 reduces relaxing effects of NO
and increases those of H2 O2 in resistance artery smooth muscle of patients with
cardiovascular disease. Arterial segments, dissected from the parietal
pericardium of 39 cardiothoracic surgery patients, were studied by myography
during amplitude-matched contractions induced by K+ , the TXA2 analogue U46619 or
ET-1. Effects of the NO donor Na-nitroprusside (SNP) and of exogenous H2 O2 were
recorded in the absence and presence of inhibitors of cyclooxygenases, NO
synthases and small and intermediate conductance calcium-activated K+ channels.
During contractions induced by either of the three stimuli, the potency of SNP
did not differ and was not modified by the inhibitors. In vessels contracted with
ET-1, the potency of H2 O2 was on average and in terms of interindividual
variability considerably larger than in K+ -contracted vessels. Both differences
were not statistically significant in the presence of inhibitors of mechanisms of
endothelium-dependent vasodilatation. In resistance arteries from patients with
cardiovascular disease, ET-1 does not selectively modify smooth muscle relaxing
responses to NO or H2 O2 . Furthermore, the candidate endothelium-derived
relaxing factor H2 O2 also acts as an endothelium-dependent vasodilator.
PMID- 28686358
TI - President's Letter July 2017.
PMID- 28686359
TI - Changing of the guard at Depression and Anxiety.
PMID- 28686357
TI - Homozygous null variant in CRADD, encoding an adaptor protein that mediates
apoptosis, is associated with lissencephaly.
AB - Lissencephaly is a severe malformation of cortical development, most often
attributed to abnormalities in neuronal migration. It is associated with a severe
prognosis including developmental delay, intellectual disability, and seizures.
Lissencephaly can be reliably diagnosed during late gestation by neurosonography
or fetal magnetic resonance imaging (MRI). We report two sibling male fetuses who
were diagnosed with delayed cortical sulcation highly suggestive of lissencephaly
during late pregnancy. After receiving genetic counseling, the parents elected to
terminate the pregnancies based on the neuroradiological findings and the
associated severe prognosis. Whole exome sequencing (WES) of an affected fetus,
and subsequent Sanger sequencing of the second fetus, revealed a homozygous
frameshift variant in CRADD, which encodes an adaptor protein that interacts with
PIDD and caspase-2 to initiate apoptosis. Biallelic variants in this gene have
been recently reported to cause "thin" lissencephaly and intellectual disability.
Interestingly, the allegedly healthy father was also found to be homozygous for
the variant, prompting evaluation by brain MRI which revealed hypogyration. This
study underscores the phenotypic variability of pathogenic variants in CRADD and
the challenges of prenatal genetic counseling.
PMID- 28686360
TI - ?
PMID- 28686361
TI - [Checkup of the 40 years old man].
AB - According to a study published by the European Commission in 2011 and including
290 millions men from 34 different countries, among which Switzerland, the male
population has a much higher mortality and morbidity rate than its female
counterpart. When a man reaches his fortierth year, he is at the top of his
abilities in many areas : he benefits from a strong life experience and the
deficits related to aging do not impact his wellbeing yet. What about his health
? Most of the recommendations in terms of screening begin at age 50. So forties
can appear as a grey area. This article reviews the screening indicated for a
patient around forty years old. It intends to offer a complement to publications
regarding screening and prevention that are regularly published in this journal.
PMID- 28686362
TI - [Substance abuse : a men's disease ?]
AB - For biological and social reasons, men have to face pressure and incentives
towards competivity, performance and risk seeking behaviours. These put them at
risk for substance use, abuse and dependence, also in a recreational context, to
improve their performances. Men's substance use is therefore significantly higher
compared to women (2/3 of the global prevalence). The purpose of this paper is a
description of gender differences in substance use and advice to provide state of
the art screening and care of male patients. Recommendations for a " men-friendly
" consultation include : provide a space where men feel comfortable ; if
possible, give the choice between a male or a female practitioner ; use other
communication media then language only ; discuss and put in perspective the
traditional male image ; and collaborate with the patient.
PMID- 28686363
TI - [" Doctor, I have a little erection problem ! "].
AB - Erectile dysfunction (ED) is a common condition that affects nearly one in three
men age 50 and more than one in two after 70 years. It is often multifactorial
and shares risk factors with coronary heart disease, which is an early marker.
Its management involves an etiological research, a modifiable risk factors
correction and often a treatment with phosphodiesterase type 5 inhibitors (IPDE
5). Follow-up should ensure the effectiveness of treatment and the presence of
side effects that could affect medication compliance. Specialized expertise
(mainly the urologist, psychiatrist, endocrinologist and cardiologist) is
required on a case by case depending on comorbidities, the need for further
investigations or no satisfactory IPDE-5 treatment response.
PMID- 28686364
TI - [Men and depression].
AB - Depression is one of the most frequently encountered psychiatric disease in the
primary care setting, source of enormous suffering for the ill and for his/her
entourage. Classical features of the disease in women are usually well known.
This article's goal is to highlight the masculine specificities of depression,
sometimes poorly known.
PMID- 28686365
TI - [Men and violence, a subject little known by general practitioners].
AB - Violence in men represents a global health burden and a serious problem of public
health, with severe repercussions on physical, psychic and social health. The
cost is very high for society. Men are often the authors of violence, but they
also can be victims or witnesses. Violence presents itself under diverse forms
and differently affects women and men in the various phases of their life and
also depends from specific features, such as social status, sexual orientation
and morbidities. We propose an overview of several points concerning violence in
men that are relevant for general practice.
PMID- 28686366
TI - [The hand : review of the main pathologies for the primary care physician].
AB - The general practitioner is often the first person to have to assess and treat a
patient complaining about his hand, especially in areas far away from an
emergency health center. The hand is the largest sensitive area of our cortex. It
is the most used part of our body and is therefore prone to traumas, cuts,
infections, tendinous inflammation and compressive nerve disorders. This article
summarises the main pathologies a primary care physician has to deal with.
PMID- 28686367
TI - ?
PMID- 28686368
TI - ?
PMID- 28686369
TI - ?
PMID- 28686370
TI - ?
PMID- 28686371
TI - ?
PMID- 28686372
TI - ?
PMID- 28686373
TI - ?
PMID- 28686374
TI - [Spatial navigation : brief overview of the medicine and physiology Nobel prize
2014].
AB - Various cells of the thalamus, hippocampus, and the medial entorhinal cortex
plays a crucial role in spatial navigation ability. The highlighting of these
cells and the understanding of their functioning by John O'Keefe, May-Britt and
Edvard Moser have earned them the Nobel Prize for Medicine and Physiology in
2014. The vision, olfaction, and the vestibular system contribute to this complex
system. These observations may well explain why patients with vestibular disorder
complain of spatial disorientation, often a source of deep anxiety.
PMID- 28686375
TI - [Vestibular and visual stimulation : simultaneous perception or not ?]
AB - The human brain is able to consider that two sensory stimuli are synchronous
while they activate the cortex with some delay because they follow different
neurological pathways. This process is only possible if the time interval between
the two stimuli does not exceed a certain limit, called "Temporal Binding Window"
(TBW). Studies of this parameter, involving the vestibular perception, are
difficult because subjects must be moved, which generates parasitic
proprioceptive information. By cons, in patients equipped with a vestibular
implant, it is possible to generate a vestibular perception selectively by
electrical stimulation of the vestibular nerve. These patients are therefore an
unique model to study the TBW between visual and vestibular perception.
PMID- 28686376
TI - [Otoscopic pitfall : the congenital cholesteatoma].
AB - The congenital cholesteatoma is a rare benign tumor whose diagnosis is mainly
made during childhood. Otoscopic examination shows a white retrotympanic
collection with or without hearing loss. In case of a late diagnosis, the disease
will spread to the surrounding structures, leading to ossicules destruction,
facial palsy, sensorineural hearing loss and vestibular dysfunction. Surgery is
the therapeutic gold-standard, with different techniques chosen based on the
cholesteatoma's extension. Patient should benefit from a long term medical and
radiological (MRI) follow-up.
PMID- 28686377
TI - [Airways access in cannot intubate situation : cricothyrotomy].
AB - In case of impossible intubation /oxygenation because of an upper airways
obstruction, a cricothyrotomy is indicated. It is a relative simple and safe
procedure that may be life saving. A blade, a tube and one's index finger are the
only tools needed. The procedure can be done anywhere and every physician should
be able to perform it. Several devices have been developed to try to improve it's
success rate ; on the contrary, they render the task more complicated and lead to
double failure rates with associated lesions, as described in our comparative
study. The aim of this article is to recall the technique and make doctors that
are not familiar with the use of a knife feel more confident. We emphasize on the
use of a finger (index) to facilitate the procedure.
PMID- 28686378
TI - [Common benign lesions of the vocal fold : diagnostic criteria and management].
AB - The vocal cord or vocal fold is a remarkable structure, capable to support
significant physical constraints. When the voice malmenage becomes chronic, it
may appear an organic alteration causing nodules, polyps or Reinke edema even a
lesion of the posterior glottis, the granuloma. These lesions are benign but lead
to dysphonia that can be invalidating. Treatment can be a speech therapy with
correction of breath and posture and, in some cases, a surgical treatment. In
this article, we describe these common lesions with their histological
characteristics and pathophysiological hypotheses which lead to their appearance
and treatment.
PMID- 28686379
TI - [Anterior semicircular canal Benign Paroxysmal Positional Vertigo].
AB - Anterior semicircular canal Benign Paroxysmal Positional Vertigo (antBPPV) is the
rarest form of semicircular canalolithiasis, corresponding to about 1-2 % of the
BPPV. The diagnosis is obtained by either the Dix-Hallpike maneuver or the
straight head hanging positioning maneuver, which provoke a characteristic
positional down-beating nystagmus. This vertical nystagmus can be associated with
a torsional component that helps in localizing the affected side. The
differential diagnosis of antBPPV includes the various central lesions that
produce vertical down beating nystagmus (posterior fossa). Several liberatory
maneuvers have been proposed for the treatment of antBPPV, but still need
standardization.
PMID- 28686380
TI - [Health and healthcare of homeless persons].
AB - Homelessness is a complex issue linked to poverty and structural conditions. It
is increasing in Western countries with younger people and multiple generations
being affected. Hard and unstable living conditions and inappropriate access to
care predispose people to increase morbidity with poor health outcomes. This
article reviews recent evidence about homeless health and strategies to improve
health outcomes while harnessing societal benefits.
PMID- 28686381
TI - ?
PMID- 28686382
TI - ?
PMID- 28686383
TI - ?
PMID- 28686384
TI - ?
PMID- 28686385
TI - ?
PMID- 28686386
TI - ?
PMID- 28686387
TI - ?
PMID- 28686388
TI - ?
PMID- 28686389
TI - ?
PMID- 28686390
TI - ?
PMID- 28686391
TI - ?
PMID- 28686392
TI - ?
PMID- 28686393
TI - [Mycoplasma pneumoniae: update and new challenges].
AB - Mycoplasma pneumoniae is a frequent cause of community acquired pneumonia,
especially in children. Discovered by Eaton in the 1940s, it has long been
considered as a virus, in part because of its difficult growth in cultures. M.
pneumoniae can cause many complications, some of which are severe such as
dermatological lesions or affections of the central nervous system. The
laboratory diagnosis of M. pneumoniae is difficult, notably because of the
fastidious growth conditions, the persistence of IgM antibody after acute
infection and the debated existence of asymptomatic carriers. In recent years,
the spread of mutants resistant to macrolides caused an additional challenge
linked to this pathogen.
PMID- 28686394
TI - [Antibiotic resistance : situation in Europe and Switzerland, and impact for the
physician].
AB - Antibiotic-resistant bacteria constitute a major public health challenge
worldwide. In Europe and Switzerland, the incidence of infections due to
methicillin-resistant S. aureus has been decreasing during the recent years. But
common Enterobacteriaceae, such as E. coli and K. pneumoniae are more and more
resistant, causing therapeutic difficulties, also in the outpatient setting and
for benign infections. To fight this increasing problem, any physician has to
apply simple preventive measures against the spread of resistant bacteria during
care, and to prevent their selection by an appropriate antibiotic use, including
the adjustment of the antibacterial spectrum, right dosage and short duration.
PMID- 28686395
TI - [Clostridium septicum aortitis : case report and update on infectious aortitis].
AB - A case of Clostridium septicum aortitis is reported. The patient did not present
any colon tumor. She died in spite of surgery and i.v. antibiotics. To date C.
septicum has been reported only in about 40 cases of infectious aortitis, a
disease with unspecific clinical presentation and a high mortality rate. A high
index of suspicion is warranted for an early diagnosis which can be made mainly
by blood cultures and contrast-enhanced CT-scan. Only starting without delay a
treatment that combines antibiotics with surgery can improve a prognosis that
remains nevertheless globally bad.
PMID- 28686397
TI - [Preanalytical step in bacteriology : a practical overview for family
physicians].
AB - Physicians play a key role in the accuracy of bacteriological results by
appropriate prescription and the quality of sample collection, preservation and
transport. Samples for diagnostic purposes are of use if analysis results have an
impact on the therapeutic approach. They have minimal risk of contamination, are
usually obtained invasively, and may be targeted to detection of specific
bacteria. Physicians should refer to the laboratory technical manual to provide
proper sample quality. Furthermore, they have to provide clinical and
administrative information to the microbiologist, because the laboratory
analytical process depends on these. Close collaboration between physicians and
microbiologists is essential.
PMID- 28686398
TI - [Leishmaniasis : an infection of travellers and migrants].
AB - Leishmaniasis is an infection of the tropical to temperate zone, occasionally
imported in our regions by travellers and migrants. Leishmania parasites are
transmitted by the sting of a sand fly, Phlebotomus or Lutzomyia, and causes two
clinical syndromes with either cutaneous, also mucosal, or disseminated
involvement. Clinical suspicion needs a confirmation by the detection of the
parasite. The treatment is adapted to the patient, the clinical presentation, the
region, the species and the availability. Cutaneous leishmaniasis can be observed
only or treated by topical or systemic regimens. Visceral leishmaniasis is a
progressive illness, in most cases mortal, particularly in the immunocompromised
patient. It requires systemic treatment.
PMID- 28686396
TI - [Recommendations for the vaccination of pregnant women : a booster injection].
AB - For several decades we have avoided the immunisation of pregnant women, with the
only exception being that of the tetanus vaccination in the absence of a previous
basic immunisation. Nowadays, it is strongly advised to give several vaccines
specifically during pregnancy : maternal immunisations against pertussis and
influenza have been shown to prevent complications in both the foetus and the
newborn as well as the woman during pregnancy and after delivery. This article
aims to review these recommendations, their rationale and to address potential
concerns that are often raised by physicians and patients. Finally, some
practical aspects of vaccine administration are detailed.
PMID- 28686399
TI - [Reflectance confocal microscopy : what future for dermatology ?]
AB - Reflectance confocal microscopy is a non invasive imaging technique which
provides in vivo and real time images of different skin tissues with a resolution
close to histology, however with a depth limited to superficial dermis.The first
lesions that were morphologically analyzed are melanocytic lesions. Reflectance
confocal microscopy has been used for about ten years in dermatology. Its
progressive improvement over the years has allowed it to be an efficient tool for
diagnosing cutaneous tumors. It has been developed for inflammatory dermatosis,
cutaneous infections, angiomas, cosmetology. Furthermore, it is also used to
delimit the edges of lesions or the area to biopsy. This cutaneous imaging
technique represents a major innovation and has its place in dermatological
practice.
PMID- 28686400
TI - ?
PMID- 28686401
TI - ?
PMID- 28686402
TI - ?
PMID- 28686403
TI - ?
PMID- 28686404
TI - ?
PMID- 28686405
TI - ?
PMID- 28686406
TI - ?
PMID- 28686407
TI - Rapid Large-Scale Assembly and Pattern Transfer of One-Dimensional Gold Nanorod
Superstructures.
AB - The utility of gold nanorods for plasmonic applications largely depends on the
relative orientation and proximity of the nanorods. Though side-by-side or
chainlike nanorod morphologies have been previously demonstrated, a simple
reliable method to obtain high-yield oriented gold nanorod assemblies remains a
significant challenge. We present a facile, scalable approach which exploits
meniscus drag, evaporative self-assembly, and van der Waals interactions to
precisely position and orient gold nanorods over macroscopic areas of 1D
nanostructured substrates. By adjusting the ratio of the nanorod diameter to the
width of the nanochannels, we demonstrate the formation of two highly desired
translationally ordered nanorod patterns. We further demonstrate a method to
transfer the aligned nanorods into a polymer matrix which exhibits anisotropic
optical properties, allowing for rapid fabrication and deployment of flexible
optical and electronic materials in future nanoscale devices.
PMID- 28686408
TI - Mechanism of Allosteric Inhibition of the Enzyme IspD by Three Different Classes
of Ligands.
AB - Enzymes of the nonmevalonate pathway of isoprenoid biosynthesis are attractive
targets for the development of herbicides and drugs against infectious diseases.
While this pathway is essential for many pathogens and plants, mammals do not
depend on it for the synthesis of isoprenoids. IspD, the third enzyme of the
nonmevalonate pathway, is unique in that it has an allosteric regulatory site. We
elucidated the binding mode of phenylisoxazoles, a new class of allosteric
inhibitors. Allosteric inhibition is effected by large conformational changes of
a loop region proximal to the active site. We investigated the different roles of
residues in this loop by mutation studies and identified repulsive interactions
with Asp291 and Asp292 to be responsible for inhibition. Crystallographic data
and the response of mutant enzymes to three different classes of allosteric
inhibitors provide an in-depth understanding of the allosteric mechanism. The
obtained mutant enzymes show selective resistance to allosteric inhibitors and
provide conceptually valuable information for future engineering of herbicide
resistant crops. We found that the isoprenoid precursors IPP and DMAPP are
natural inhibitors of Arabidopsis thaliana IspD; however, they do not seem to
bind to the allosteric site.
PMID- 28686410
TI - Nanoscale Bandgap Tuning across an Inhomogeneous Ferroelectric Interface.
AB - We report nanoscale bandgap engineering via a local strain across the
inhomogeneous ferroelectric interface, which is controlled by the visible-light
excited probe voltage. Switchable photovoltaic effects and the spectral response
of the photocurrent were explored to illustrate the reversible bandgap variation
(~0.3 eV). This local-strain-engineered bandgap has been further revealed by in
situ probe-voltage-assisted valence electron energy-loss spectroscopy (EELS).
Phase-field simulations and first-principle calculations were also employed for
illustration of the large local strain and the bandgap variation in ferroelectric
perovskite oxides. This reversible bandgap tuning in complex oxides demonstrates
a framework for the understanding of the optically related behaviors
(photovoltaic, photoemission, and photocatalyst effects) affected by order
parameters such as charge, orbital, and lattice parameters.
PMID- 28686409
TI - Structural Characterization of Biofunctionalized Gold Nanoparticles by Ultrahigh
Resolution Mass Spectrometry.
AB - Biofunctionalized gold nanoparticles (AuNPs) enable innovative translational
research and development in biomedicine. Biomolecules such as peptides, proteins,
lipids, and carbohydrates can be assembled onto AuNPs to yield nanomaterials with
unique properties for applications in imaging, photothermal therapy, vaccination
strategies, and drug delivery. The characterization of functionalized AuNPs still
remains an analytical challenge that normally requires the combination of
multiple techniques. Laser desorption/ionization (LDI) and matrix-assisted LDI
(MALDI) have been applied successfully in combination with time-of-flight (TOF)
mass spectrometry (MS) for the analysis of the surface chemistry of AuNPs
functionalized with synthetic ligands, however only for ligands with a molecular
mass limited to 1000 Da. TOF-MS-based approaches in addition exhibit limited
performance in terms of mass resolution and MS/MS possibilities. To overcome
these limitations, we designed an approach for the analysis of AuNPs based on
ultrahigh resolution Fourier transform ion cyclotron resonance (FTICR) MS and a
combination of LDI and MALDI. To illustrate the performance of the method, we
present a comprehensive characterization of the surface chemistry of AuNPs
conjugated via a thiol-ending linker to either the ovalbumin peptide (OVA 323
339), the Lewis X antigen (Galbeta1-4[Fucalpha1-3]GlcNAcbeta1) trisaccharide, the
tetramannoside Manalpha1-2Manalpha1-2Manalpha1-3Manalpha1, or a mixture of both
carbohydrates. Collision-induced dissociation (CID) was used to characterize the
structure of pseudomolecular ions generated by LDI/MALDI in-depth. These included
[M + H]+ and [M + Na]+, and importantly also [M + Au]+ and [M + 2Au-H]+ ions.
This first observation of gold-containing pseudomolecular ions provides direct
evidence for the Au-conjugation of ligands. In addition, we show the
applicability of the method to monitor proteolytic cleavage of peptides that are
conjugated to the AuNP surface. The presented LDI/MALDI-FTICR-MS and MS/MS
approach will be applicable to the characterization of a wide range of
functionalized AuNPs.
PMID- 28686411
TI - Observation of Room-Temperature Magnetoresistance in Monolayer MoS2 by
Ferromagnetic Gating.
AB - Room-temperature magnetoresistance (MR) effect is observed in heterostructures of
wafer-scale MoS2 layers and ferromagnetic dielectric CoFe2O4 (CFO) thin films.
Through the ferromagnetic gating, an MR ratio of -12.7% is experimentally
achieved in monolayer MoS2 under 90 kOe magnetic field at room temperature (RT).
The observed MR ratio is much higher than that in previously reported nonmagnetic
metal coupled with ferromagnetic insulator, which generally exhibited MR ratio of
less than 1%. The enhanced MR is attributed to the spin accumulation at the
heterostructure interface and spin injection to the MoS2 layers by the strong
spin-orbit coupling effect. The injected spin can contribute to the spin current
and give rise to the MR by changing the resistance of MoS2 layers. Furthermore,
the MR effect decreases as the thickness of MoS2 increases, and the MR ratio
becomes negligible in MoS2 with thickness more than 10 layers. Besides, it is
interesting to find a magnetic field direction dependent spin Hall
magnetoresistance that stems from a combination of the spin Hall and the inverse
spin Hall effects. Our research provides an insight into exploring RT MR in
monolayer materials, which should be helpful for developing ultrathin magnetic
storage devices in the atomically thin limit.
PMID- 28686412
TI - Field-Assisted Splitting of Pure Water Based on Deep-Sub-Debye-Length Nanogap
Electrochemical Cells.
AB - Owing to the low conductivity of pure water, using an electrolyte is common for
achieving efficient water electrolysis. In this paper, we have fundamentally
broken through this common sense by using deep-sub-Debye-length nanogap
electrochemical cells to achieve efficient electrolysis of pure water (without
any added electrolyte) at room temperature. A field-assisted effect resulted from
overlapped electrical double layers can greatly enhance water molecules
ionization and mass transport, leading to electron-transfer limited reactions. We
have named this process "virtual breakdown mechanism" (which is completely
different from traditional mechanisms) that couples the two half-reactions
together, greatly reducing the energy losses arising from ion transport. This
fundamental discovery has been theoretically discussed in this paper and
experimentally demonstrated in a group of electrochemical cells with nanogaps
between two electrodes down to 37 nm. On the basis of our nanogap electrochemical
cells, the electrolysis current density from pure water can be significantly
larger than that from 1 mol/L sodium hydroxide solution, indicating the much
better performance of pure water splitting as a potential for on-demand clean
hydrogen production.
PMID- 28686413
TI - Atomically Thin Layers of Graphene and Hexagonal Boron Nitride Made by Solvent
Exfoliation of Their Phosphoric Acid Intercalation Compounds.
AB - The development of scalable and reliable techniques for the production of the
atomically thin layers of graphene and hexagonal boron nitride (h-BN) in bulk
quantities could make these materials a powerful platform for devices and
composites that impact a wide variety of technologies (Nature 2012, 490, 192
200). To date a number of practical exfoliation methods have been reported that
are based on sonicating or stirring powdered graphite or h-BN in common solvents.
However, the products of these experiments consist mainly of few-layer sheets and
contain only a small fraction of monolayers. A possible reason for this is that
splitting the crystals into monolayers starts from solvent intercalation, which
must overcome the substantial interlayer cohesive energy (120-720 mJ/m2) of the
van der Waals solids. Here we show that the yield of the atomically thin layers
can be increased to near unity when stage-1 intercalation compounds of phosphoric
acid are used as starting materials. The exfoliation to predominantly monolayers
was achieved by stirring them in medium polarity organic solvents that can form
hydrogen bonds. The exfoliation process does not disrupt the sp2 pi-system of
graphene and is gentle enough to allow the preparation of graphene and h-BN
monolayers that are tens of microns in their lateral dimensions.
PMID- 28686414
TI - Stimuli-Responsive "Cluster Bomb" for Programmed Tumor Therapy.
AB - In this paper, mesoporous silica nanoparticle (MSN) loaded with doxorubicin (DOX)
and capped with tumor-homing/-penetrating peptide tLyP-1-modified tungsten
disulfide quantum dots (WS2-HP) was designed and applied as a stimuli-responsive
"Cluster Bomb" for high-performance tumor suppression. The peptide tLyP-1 on the
surface can both facilitate the homing of DOX@MSN-WS2-HP to 4T1 tumor and greatly
enhance the penetration of WS2-HP in tumor. The benzoic-imine bonds as the
linkers between "bomblets" and "dispenser" are stable under normal physical
conditions and quite labile at pH 6.8. After arriving at the mild acidic tumor
microenvironment, the nanoplatform can rapidly break into two parts: (1)
electropositive DOX@MSN-NH2 for efficient chemotherapy on surface tumor cells and
(2) small-sized WS2-HP with improved tumor penetrating ability for near-infrared
(NIR)-light-triggered photothermal therapy (PTT) among deep-seated tumor cells.
Having killed the tumor cells in different depths, DOX@MSN-WS2-HP exhibited
significant antitumor effect, which will find great potential in clinical trials.
PMID- 28686415
TI - High-Resolution Transfer Printing of Graphene Lines for Fully Printed, Flexible
Electronics.
AB - Pristine graphene inks show great promise for flexible printed electronics due to
their high electrical conductivity and robust mechanical, chemical, and
environmental stability. While traditional liquid-phase printing methods can
produce graphene patterns with a resolution of ~30 MUm, more precise techniques
are required for improved device performance and integration density. A high
resolution transfer printing method is developed here capable of printing
conductive graphene patterns on plastic with line width and spacing as small as
3.2 and 1 MUm, respectively. The core of this method lies in the design of a
graphene ink and its integration with a thermally robust mold that enables
annealing at up to ~250 degrees C for precise, high-performance graphene
patterns. These patterns exhibit excellent electrical and mechanical properties,
enabling favorable operation as electrodes in fully printed electrolyte-gated
transistors and inverters with stable performance even following cyclic bending
to a strain of 1%. The high resolution coupled with excellent control over the
line edge roughness to below 25 nm enables aggressive scaling of transistor
dimensions, offering a compelling route for the scalable manufacturing of
flexible nanoelectronic devices.
PMID- 28686416
TI - Decorating Self-Assembled Peptide Cages with Proteins.
AB - An ability to organize and encapsulate multiple active proteins into defined
objects and spaces at the nanoscale has potential applications in biotechnology,
nanotechnology, and synthetic biology. Previously, we have described the design,
assembly, and characterization of peptide-based self-assembled cages (SAGEs).
These ~100 nm particles comprise thousands of copies of de novo designed peptide
based hubs that array into a hexagonal network and close to give caged
structures. Here, we show that, when fused to the designed peptides, various
natural proteins can be co-assembled into SAGE particles. We call these
constructs pSAGE for protein-SAGE. These particles tolerate the incorporation of
multiple copies of folded proteins fused to either the N or the C termini of the
hubs, which modeling indicates form the external and internal surfaces of the
particles, respectively. Up to 15% of the hubs can be functionalized without
compromising the integrity of the pSAGEs. This corresponds to hundreds of copies
giving mM local concentrations of protein in the particles. Moreover, and
illustrating the modularity of the SAGE system, we show that multiple different
proteins can be assembled simultaneously into the same particle. As the peptide
protein fusions are made via recombinant expression of synthetic genes, we
envisage that pSAGE systems could be developed modularly to actively encapsulate
or to present a wide variety of functional proteins, allowing them to be
developed as nanoreactors through the immobilization of enzyme cascades or as
vehicles for presenting whole antigenic proteins as synthetic vaccine platforms.
PMID- 28686417
TI - Evaluating the Financial Vulnerability of a Major Electric Utility in the
Southeastern U.S. to Drought under Climate Change and an Evolving Generation Mix.
AB - There is increasing recognition of the vulnerability of electric power systems to
drought and the potential for both climate change and a shifting generation mix
to alter this vulnerability. Nonetheless, the considerable research in this area
has not been synthesized to inform electric utilities with respect to a key
factor that influences their decisions about critical infrastructure: financial
risk for shareholders. This study addresses this gap in knowledge by developing a
systems framework for assessing the financial exposure of utilities to drought,
with further consideration of the effects of climate change and a shifting
generation mix. We then apply this framework to a major utility in the
Southeastern U.S. Results suggest that extreme drought could cause profit
shortfalls of more than $100 million if water temperature regulations are
strictly enforced. However, even losses of this magnitude would not significantly
impact returns for shareholders. This may inadvertently reduce pressure
internally at utilities to incorporate drought vulnerability into long-term
strategic planning, potentially leaving utilities and their customers at greater
risk in the future.
PMID- 28686418
TI - Cation-Eutectic Transition via Sublattice Melting in CuInP2S6/In4/3P2S6 van der
Waals Layered Crystals.
AB - Single crystals of the van der Waals layered ferrielectric material CuInP2S6
spontaneously phase separate when synthesized with Cu deficiency. Here we
identify a route to form and tune intralayer heterostructures between the
corresponding ferrielectric (CuInP2S6) and paraelectric (In4/3P2S6) phases
through control of chemical phase separation. We conclusively demonstrate that Cu
deficient Cu1-xIn1+x/3P2S6 forms a single phase at high temperature. We also
identify the mechanism by which the phase separation proceeds upon cooling. Above
500 K both Cu+ and In3+ become mobile, while P2S64- anions maintain their
structure. We therefore propose that this transition can be understood as
eutectic melting on the cation sublattice. Such a model suggests that the
transition temperature for the melting process is relatively low because it
requires only a partial reorganization of the crystal lattice. As a result,
varying the cooling rate through the phase transition controls the lateral extent
of chemical domains over several decades in size. At the fastest cooling rate,
the dimensional confinement of the ferrielectric CuInP2S6 phase to nanoscale
dimensions suppresses ferrielectric ordering due to the intrinsic ferroelectric
size effect. Intralayer heterostructures can be formed, destroyed, and re-formed
by thermal cycling, thus enabling the possibility of finely tuned ferroic
structures that can potentially be optimized for specific device architectures.
PMID- 28686419
TI - Factors Determining the Rate and Selectivity of 4e-/4H+ Electrocatalytic
Reduction of Dioxygen by Iron Porphyrin Complexes.
AB - Reactivity as well as selectivity are crucial in the activation and
electrocatalytic reduction of molecular oxygen. Recent developments in the
understanding of the mechanism of electrocatalytic O2 reduction by iron porphyrin
complexes in situ using surface enhanced resonance Raman spectroscopy coupled to
rotating disc electrochemistry (SERRS-RDE) in conjunction with H/D isotope
effects on electrocatalytic current reveals that the rate of O2 reduction, ~104
to 105 M-1 s-1 for simple iron porphyrins, is limited by the rate of O-O bond
cleavage of an intermediate ferric peroxide species (FeIII-OOH). SERRS-RDE probes
the system in operando when it is under steady state such that any intermediate
species that has a greater rate of formation relative to its rate of decay,
including the rate determining species, would accumulate and can be identified.
This technique is particularly well suited to investigate iron porphyrin
electrocatalysts as the intense symmetric ligand vibrations allow determination
of the oxidation and spin states of the bound iron with high fidelity. The rate
of O2 reduction could be tuned up by 3 orders of magnitude by incorporating
residues in the catalyst design that can exert "push" or "pull" effects, that is,
axial phenolate and thiolate ligands and distal arginine residues. Similarly the
rate of O-O bond cleavage can be enhanced by several orders of magnitude upon
incorporating a distal Cu site and installing the active site in a hydrophobic
protein environment in synthetic models and biosynthetic protein scaffolds. The
selectivity, however, is solely determined by the site of protonation of a ferric
peroxide (FeIII-OOH) intermediate and can be governed by installing preorganized
second sphere residues in the distal pocket. The 4e-/4H+ reduction of O2 entails
protonation of the distal oxygen of the FeIII-OOH species, while 2e-/2H+
reduction requires the proximal oxygen to be protonated. Mechanistic
investigations of CO2 reduction by iron porphyrins reveal that the rate
determining step is the C-O bond cleavage of a FeII-COOH species analogous to the
O-O bond cleavage step of a FeIII-OOH species in O2 reduction. The selectivity,
resulting in either CO or HCOOH, is determined by the site of protonation of this
species. These similarities suggests that the chemical principles governing the
rate and selectivity of reduction of small molecules like O2, CO2, NOx, and SOx
may be quite similar in nature.
PMID- 28686420
TI - Mechanistic Insights from Discrete Molecular Dynamics Simulations of Pesticide
Nanoparticle Interactions.
AB - Nanoscale particles have the potential to modulate the transport, lifetimes, and
ultimate uptake of pesticides that may otherwise be bound to agricultural soils.
Engineered nanoparticles provide a unique platform for studying these
interactions. In this study, we utilized discrete molecular dynamics (DMD) as a
screening tool for examining nanoparticle-pesticide adsorptive interactions. As a
proof-of-concept, we selected a library of 15 pesticides common in the United
States and 4 nanomaterials with likely natural or incidental sources, and
simulated all possible nanoparticle-pesticide pairs. The resulting adsorption
coefficients derived from DMD simulations ranged over several orders of
magnitude, and in many cases were significantly stronger than pesticide
adsorption on clay surfaces, highlighting the significance of specific nanoscale
phases as a preferential media with which pesticides may associate. Binding was
found to be significantly enhanced by the capacity to form hydrogen bonds with
slightly hydroxylated fullerols, highlighting the importance of considering the
precise nature of weathered nanomaterials as opposed to pristine precursors.
Results were compared to experimental adsorption studies using selected
pesticides, with a Pearson correlation coefficient of 0.97.
PMID- 28686421
TI - Amplification of Circularly Polarized Luminescence through Triplet-Triplet
Annihilation-Based Photon Upconversion.
AB - Amplification of circularly polarized luminescence (CPL) is demonstrated in a
triplet-triplet annihilation-based photon upconversion (TTA-UC) system. When
chiral binaphthyldiamine acceptors are sensitized with an achiral Pt(II)
octaethylporphine (PtOEP) in solution, upconverted circularly polarized
luminescence (UC-CPL) were observed for the first time, in which the positive or
negative circularly polarized emission could be obtained respectively, following
the molecular chirality of the acceptors (R/S). More interestingly, one order of
magnitude amplification of the dissymmetry factor glum in UC-CPL was obtained in
comparison with the normal promoted CPL. The multistep photophysical process of
TTA-UC including triplet-triplet energy transfer (TTET) and triplet-triplet
annihilation (TTA) have been suggested to enhance the UC-CPL, which provided a
new strategy to design CPL materials with a higher dissymmetry factor.
PMID- 28686422
TI - Synthesis, Structure, and Magnetic Properties of 1D {[MnIII(CN)6][MnII(dapsc)]}n
Coordination Polymers: Origin of Unconventional Single-Chain Magnet Behavior.
AB - Two one-dimensional cyano-bridged coordination polymers, namely,
{[MnII(dapsc)][MnIII(CN)6][K(H2O)2.75(MeOH)0.5]}n.0.5n(H2O) (I) and
{[MnII(dapsc)][MnIII(CN)6][K(H2O)2(MeOH)2]}n (II), based on alternating high-spin
MnII(dapsc) (dapsc = 2,6-diacetylpyridine bis(semicarbazone)) complexes and low
spin orbitally degenerate hexacyanomanganate(III) complexes were synthesized and
characterized structurally and magnetically. Static and dynamic magnetic
measurements reveal a single-chain magnet (SCM) behavior of I with an energy
barrier of Ueff ~ 40 K. Magnetic properties of I are analyzed in detail in terms
of a microscopic theory. It is shown that compound I refers to a peculiar case of
SCM that does not fall into the usual Ising and Heisenberg limits due to
unconventional character of the MnIII-CN-MnII spin coupling resulting from a
nonmagnetic singlet ground state of orbitally degenerate complexes [MnIII(CN)6]3
. The prospects of [MnIII(CN)6]3- complex as magnetically anisotropic molecular
building block for engineering molecular magnets are critically analyzed.
PMID- 28686423
TI - Nanoparticle Uptake in Plants: Gold Nanomaterial Localized in Roots of
Arabidopsis thaliana by X-ray Computed Nanotomography and Hyperspectral Imaging.
AB - Terrestrial plants can internalize and translocate nanoparticles (NPs). However,
direct evidence for the processes driving the NP uptake and distribution in
plants is scarce at the cellular level. Here, NP-root interactions were
investigated after 10 days of exposure of Arabidopsis thaliana to 10 mg.L-1 of
negatively or positively charged gold NPs (~12 nm) in gels. Two complementary
imaging tools were used: X-ray computed nanotomography (nano-CT) and enhanced
dark-field microscopy combined with hyperspectral imaging (DF-HSI). The use of
these emerging techniques improved our ability to detect and visualize NP in
plant tissue: by spectral confirmation via DF-HSI, and in three dimensions via
nano-CT. The resulting imaging provides direct evidence that detaching border
like cells (i.e., sheets of border cells detaching from the root) and associated
mucilage can accumulate and trap NPs irrespective of particle charge. On the
contrary, border cells on the root cap behaved in a charge-specific fashion:
positively charged NPs induced a higher mucilage production and adsorbed to it,
which prevented translocation into the root tissue. Negatively charged NPs did
not adsorb to the mucilage and were able to translocate into the apoplast. These
observations provide direct mechanistic insight into NP-plant interactions, and
reveal the important function of border cells and mucilage in interactions of
plants with charged NPs.
PMID- 28686424
TI - Sub-ppt Mass Spectrometric Detection of Therapeutic Drugs in Complex Biological
Matrixes Using Polystyrene-Microsphere-Coated Paper Spray.
AB - Polystyrene (PS) is a class of polymer materials that offers great potential for
various applications. However, the applications of PS microspheres in paper spray
mass spectrometry are largely underexplored. Herein we prepared a series of PS
microspheres via a simple dispersion polymerization and then used them as coating
materials for paper spray mass spectrometry (MS) in high-sensitivity analysis of
various therapeutic drugs in complex biological matrixes. In the preparation of
PS-coated papers, the coating method was found playing a key role in determining
the performance of the resulting paper substrate in addition to other parameters
(e.g., starch type and amount, PS coating amount, and spray solvent). We also
found that as a solvent was applied on PS-coated paper for paper spray, the
analytes of interest would be first extracted out and then moved to the tip of
paper triangle for spray along with the applied solvent. In the process, the
surface energy of PS particles had a strong impact on the desorption performance
of analytes from PS-coated paper substrate, and the PS with a high surface energy
favored the elution of analytes to allow a high MS sensitivity. When the prepared
PS coated paper was used as a substrate for paper spray, it gave high sensitivity
in analysis of therapeutic drugs in various biological matrixes such as whole
blood, serum, and urine with excellent repeatability and reproducibility. In
contrast to uncoated filter paper, an improvement of 10-546-fold in sensitivity
was achieved using PS-coated paper for paper spray, and an estimated lower limit
of quantitation (LLOQs) in the range of 0.004-0.084 ng mL-1 was obtained. The
present study is significant in exploring the potential of PS for high
sensitivity MS analysis, and it provides a promising platform in the translation
of the MS technique to clinical applications.
PMID- 28686425
TI - Source-Receptor Relationship Analysis of the Atmospheric Deposition of PAHs
Subject to Long-Range Transport in Northeast Asia.
AB - The source-receptor relationship analysis of PAH deposition in Northeast Asia was
investigated using an Eulerian regional-scale aerosol chemical transport model.
Dry deposition (DD) of PAH was controlled by wind flow patterns, whereas wet
deposition (WD) depended on precipitation in addition to wind flow patterns. The
contribution of WD was approximately 50-90% of the total deposition, except
during winter in Northern China (NCHN) and Eastern Russia (ERUS) because of the
low amount of precipitation. The amount of PAH deposition showed clear seasonal
variation and was high in winter and low in summer in downwind (South Korea,
Japan) and oceanic-receptor regions. In the downwind region, the contributions
from NCHN (WD 28-52%; DD 54-55%) and Central China (CCHN) (WD 43-65%; DD 33-38%)
were large in winter, whereas self-contributions (WD 20-51%; DD 79-81%) were
relatively high in summer. In the oceanic-receptor region, the deposition amount
decreased with distance from the Asian continent. The amount of DD was strongly
influenced by emissions from neighboring domains. The contributions of WD from
NCHN (16-20%) and CCHN (28-35%) were large. The large contributions from China in
summer to the downwind region were linked to vertical transport of PAHs over the
Asian continent associated with convection.
PMID- 28686426
TI - Stereoselective and Site-Specific Allylic Alkylation of Amino Acids and Small
Peptides via a Pd/Cu Dual Catalysis.
AB - We report a stereoselective and site-specific allylic alkylation of Schiff base
activated amino acids and small peptides via a Pd/Cu dual catalysis. A range of
noncoded alpha,alpha-dialkyl alpha-amino acids were easily synthesized in high
yields and with excellent enantioselectivities (up to >99% ee). Furthermore, a
direct and highly stereoselective synthesis of small peptides with enantiopure
alpha-alkyl or alpha,alpha-dialkyl alpha-amino acids residues incorporated at
specific sites was accomplished using this dual catalyst system.
PMID- 28686427
TI - Degradation of p-Nitrophenol by Lignin and Cellulose Chars: H2O2-Mediated
Reaction and Direct Reaction with the Char.
AB - Chars and other black carbons are reactive toward certain compounds. Such
reactivity has been attributed to reduction of O2 by persistent free radicals in
the solid to H2O2, which then back-reacts with the solid to generate reactive
oxygen species (ROS; especially HO*). We studied the decomposition of p
nitrophenol (PNP) by pure lignin and cellulose chars aged in moist air or a
vacuum at room temperature for up to a month. In air, the chars chemisorbed
oxygen, a portion of which was liberated as H2O2 when the char was submerged in
water. The evolved H2O2 was simultaneously decomposed by the char. PNP reacted
predominantly in the sorbed state and only reduction products (phenol, catechol)
were identified. Aging the char in air sharply (within hours) reduced H2O2
producing capacity and free radical concentration, but more gradually reduced PNP
decay rate over the month-long period. PNP decay was only modestly suppressed (12
30%) by H2O2 removal (catalase), and had little effect on the free radical signal
(<6 radicals annihilated per 1000 PNP reacted). Contrasting with previous
studies, the results show that direct reaction of PNP with char predominates over
H2O2-dependent reactions, and the vast majority of direct-reacting sites are
nonradical in character. Nonradical sites are also responsible in part for H2O2
decomposition; in fact, H2O2 pretreatment depleted PNP reactive sites. Lignin
char was generally more reactive than cellulose char. The Fe impurity in lignin
played no role. The results are relevant to the fate of pollutants in black
carbon-rich environments and the use of carbons in remediation.
PMID- 28686428
TI - Insight-Based Approach for the Design of Integrated Local Food-Energy-Water
Systems.
AB - Society currently relies heavily on centralized production and large scale
distribution infrastructures to meet growing demands for goods and services,
which causes socioeconomic and environmental issues, particularly unsustainable
resource supply. Considering local production systems as a more sustainable
alternative, this paper presents an insight-based approach to the integrated
design of local systems providing food, energy, and water to meet local demands.
The approach offers a new hierarchical and iterative decision and analysis
procedure incorporating design principles and ability to examine design
decisions, in both synthesis of individual yet interconnected subsystems and
integrated design of resource reuse across the entire system. The approach was
applied to a case study on design of food-energy-water system for a locale in the
U.K.; resulting in a design which significantly reduced resource consumption
compared to importing goods from centralized production. The design process
produced insights into the impact of one decision on other parts of the problem,
either within or across different subsystems. The result was also compared to the
mathematical programming approach for whole system optimization from previous
work. It was demonstrated that the new approach could produce a comparable design
while offering more valuable insights for decision makers.
PMID- 28686429
TI - Understanding Charge-Transfer Characteristics in Crystalline Nanosheets of
Fullerene/(Metallo)porphyrin Cocrystals.
AB - Cocrystals in the form of crystalline nanosheets comprised of C70 and
(metallo)porphyrins were prepared by using the liquid-liquid interfacial
precipitation (LLIP) method where full control over the morphologies in the
C70/(metallo)porphyrins nanosheets has been accomplished by changing the solvent
and the relative molar ratio of fullerene to (metallo)porphyrin. Importantly, the
synergy of integrating C70 and (metallo)porphyrins as electron acceptors and
donors, respectively, into nanosheets is substantiated in the form of a near
infrared charge-transfer absorption. The presence of the latter, as reflection of
ground-state electron donor-acceptor interactions in the nanosheets, in which a
sizable redistribution of charge density from the electron-donating
(metallo)porphyrins to the electron-accepting C70 occurs, leads to a quantitative
quenching of the localized (metallo)porphyrin fluorescence. Going beyond the
ground-state characterization, excited-state electron donor-acceptor interactions
are the preclusion to a full charge transfer featuring formation of a radical ion
pair state, that is, the one-electron reduced fullerene and the one-electron
oxidized (metallo)porphyrin.
PMID- 28686430
TI - Highly Active, Nonprecious Electrocatalyst Comprising Borophene Subunits for the
Hydrogen Evolution Reaction.
AB - Developing nonprecious hydrogen evolution electrocatalysts that can work well at
large current densities (e.g., at 1000 mA/cm2: a value that is relevant for
practical, large-scale applications) is of great importance for realizing a
viable water-splitting technology. Herein we present a combined theoretical and
experimental study that leads to the identification of alpha-phase molybdenum
diboride (alpha-MoB2) comprising borophene subunits as a noble metal-free,
superefficient electrocatalyst for the hydrogen evolution reaction (HER). Our
theoretical finding indicates, unlike the surfaces of Pt- and MoS2-based
catalysts, those of alpha-MoB2 can maintain high catalytic activity for HER even
at very high hydrogen coverage and attain a high density of efficient catalytic
active sites. Experiments confirm alpha-MoB2 can deliver large current densities
in the order of 1000 mA/cm2, and also has excellent catalytic stability during
HER. The theoretical and experimental results show alpha-MoB2's catalytic
activity, especially at large current densities, is due to its high conductivity,
large density of efficient catalytic active sites and good mass transport
property.
PMID- 28686431
TI - Diastereoselective Synthesis of CF3-Containing Vicinal Diamines.
AB - The highly diastereoselective synthesis of CF3-containing vicinal diamines by a
convenient two-step procedure without the need to isolate the intermediate
products is described.
PMID- 28686432
TI - Synergistic Reinforcing Mechanisms in Cellulose Nanofibrils Composite Hydrogels:
Interfacial Dynamics, Energy Dissipation, and Damage Resistance.
AB - Engineering reversible cross-links between nanoparticles and polymer matrix is a
promising avenue to reinforce the mechanical properties of elastomers and in
particular soft hydrogels. In this work, we study a model system of composite
hydrogel reinforced with cellulose nanofibrils (CNFs), where the integration of
reversible hydrogen bonds into a lightly covalently cross-linked polyacrylamide
(PAAm) matrix. This approach yields the dual cross-linked networks with
synergistically improved strength, modulus, and toughness. The reversible nature
of the hydrogen-bonded cross-links manifests a strong strain rate (epsilon)
dependent dynamics properties. The CNF-PAAm interaction among physically adsorbed
chains on the surface of CNF is examined as a function of CNF fraction by sum
frequency generation spectroscopy. The results indicate a decrease of the number
of free -OH groups on the CNF surface. Moreover, the deformation-resting
experiments show a unique interface stiffening mechanism where the polymer chains
desorbed from the CNF surface under oscillatory shear become entangled during
resting time. The bending micromechanics test reveals that the CNF interfacial
slip imparts the capability to strengthen the composites during deformation. The
fibril pull-out process activates a series of dissipation mechanisms that
increase the crack propagation resistance. These findings advance our
understanding the role of interfacial layer in microscopic reinforcement
mechanism and provide a constitutive foundation for exploring the deformation
behaviors of the cellulosic hydrogels.
PMID- 28686433
TI - Mirror-Image Thymidine Discriminates against Incorporation of Deoxyribonucleotide
Triphosphate into DNA and Repairs Itself by DNA Polymerases.
AB - DNA polymerases are known to recognize preferably d-nucleotides over l
nucleotides during DNA synthesis. Here, we report that several general DNA
polymerases catalyze polymerization reactions of nucleotides directed by the DNA
template containing an l-thymidine (l-T). The results display that the 5'-3'
primer extension of natural nucleotides get to the end at chiral modification
site with Taq and Phanta Max DNA polymerases, but the primer extension proceeds
to the end of the template catalyzed by Deep Vent (exo-), Vent (exo-), and
Therminator DNA polymerases. Furthermore, templating l-nucleoside displays a lag
in the deoxyribonucleotide triphosphate (dNTP) incorporation rates relative to
natural template by kinetics analysis, and polymerase chain reactions were
inhibited with the DNA template containing two or three consecutive l-Ts. Most
interestingly, no single base mutation or mismatch mixture corresponding to the
location of l-T in the template was found, which is physiologically significant
because they provide a theoretical basis on the involvement of DNA polymerase in
the effective repair of l-T that may lead to cytotoxicity.
PMID- 28686434
TI - Ionic-Liquid-Based CO2 Capture Systems: Structure, Interaction and Process.
AB - The inherent structure tunability, good affinity with CO2, and nonvolatility of
ionic liquids (ILs) drive their exploration and exploitation in CO2 separation
field, and has attracted remarkable interest from both industries and academia.
The aim of this Review is to give a detailed overview on the recent advances on
IL-based materials, including pure ILs, IL-based solvents, and IL-based membranes
for CO2 capture and separation from the viewpoint of molecule to engineering. The
effects of anions, cations and functional groups on CO2 solubility and
selectivity of ILs, as well as the studies on degradability of ILs are reviewed,
and the recent developments on functionalized ILs, IL-based solvents, and IL
based membranes are also discussed. CO2 separation mechanism with IL-based
solvents and IL-based membranes are explained by combining molecular simulation
and experimental characterization. Taking into consideration of the applications
and industrialization, the recent achievements and developments on the transport
properties of IL fluids and the process design of IL-based processes are
highlighted. Finally, the future research challenges and perspectives of the
commercialization of CO2 capture and separation with IL-based materials are
posed.
PMID- 28686436
TI - Effects of All-Electron Basis Sets and the Scalar Relativistic Corrections in the
Structure and Electronic Properties of Niobium Clusters.
AB - In this paper, an augmented all-electron double-zeta basis set is used in
calculations of the structure and electronic properties of small niobium
clusters. The B3PW91 and M06 DFT functionals with and without second order
Douglas-Kroll-Hess (DKH) scalar relativistic corrections are also utilized.
Furthermore, an additional d Gaussian type function is introduced in the standard
basis sets in order to improve the description of the clusters orbitals in the
valence band. Our findings show that the extra d function is important to yield
accurate results of electronic properties and, in addition, the DKH corrections
can be relevant when the all-electron basis sets are used in the calculations.
Our best results are obtained with the M06 functional together with the DKH
second order corrections and with the extra d function added to the all-electron
basis set.
PMID- 28686437
TI - Mechanisms Underlying Ion Transport in Polymerized Ionic Liquids.
AB - We report the results of atomistic molecular dynamics simulations informed by
quantum-mechanically parametrized force fields, which identify the mechanisms
underlying ion motion and diffusivities in poly(1-butyl-3-vinylimidazolium
hexafluorophosphate) polymerized ionic liquid (polyIL) electrolytes. Our results
demonstrate that anion transport in polyILs occurs through a mechanism involving
intra- and intermolecular ion hopping through formation and breaking of ion
associations involving four polymerized cationic monomers bonded to two different
polymer chains. The resulting ion mobilities are directly correlated to the
average lifetimes of the ion-associations. Such a trend is demonstrated to
contrast with the behavior in pure ILs, wherein structural relaxations and the
associated times are dominant mechanism. Our results establish the basis for
experimental findings that reported ion transport in polyILs to be decoupled from
polymer segmental relaxations.
PMID- 28686435
TI - Animal Feces Contribute to Domestic Fecal Contamination: Evidence from E. coli
Measured in Water, Hands, Food, Flies, and Soil in Bangladesh.
AB - Fecal-oral pathogens are transmitted through complex, environmentally mediated
pathways. Sanitation interventions that isolate human feces from the environment
may reduce transmission but have shown limited impact on environmental
contamination. We conducted a study in rural Bangladesh to (1) quantify domestic
fecal contamination in settings with high on-site sanitation coverage; (2)
determine how domestic animals affect fecal contamination; and (3) assess how
each environmental pathway affects others. We collected water, hand rinse, food,
soil, and fly samples from 608 households. We analyzed samples with IDEXX
Quantitray for the most probable number (MPN) of E. coli. We detected E. coli in
source water (25%), stored water (77%), child hands (43%), food (58%), flies
(50%), ponds (97%), and soil (95%). Soil had >120 000 mean MPN E. coli per gram.
In compounds with vs without animals, E. coli was higher by 0.54 log10 in soil,
0.40 log10 in stored water and 0.61 log10 in food (p < 0.05). E. coli in stored
water and food increased with increasing E. coli in soil, ponds, source water and
hands. We provide empirical evidence of fecal transmission in the domestic
environment despite on-site sanitation. Animal feces contribute to fecal
contamination, and fecal indicator bacteria do not strictly indicate human fecal
contamination when animals are present.
PMID- 28686438
TI - Globally-Optimized Local Pseudopotentials for (Orbital-Free) Density Functional
Theory Simulations of Liquids and Solids.
AB - The accuracy of local pseudopotentials (LPSs) is one of two major determinants of
the fidelity of orbital-free density functional theory (OFDFT) simulations. We
present a global optimization strategy for LPSs that enables OFDFT to reproduce
solid and liquid properties obtained from Kohn-Sham DFT. Our optimization
strategy can fit arbitrary properties from both solid and liquid phases, so the
resulting globally optimized local pseudopotentials (goLPSs) can be used in solid
and/or liquid-phase simulations depending on the fitting process. We show three
test cases proving that we can (1) improve solid properties compared to our
previous bulk-derived local pseudopotential generation scheme; (2) refine
predicted liquid and solid properties by adding force matching data; and (3)
generate a from-scratch, accurate goLPS from the local channel of a non-local
pseudopotential. The proposed scheme therefore serves as a full and improved LPS
construction protocol.
PMID- 28686439
TI - Theoretical Prediction of Si2-Si33 Absorption Spectra.
AB - The optical absorption spectra of Si2-Si33 clusters were systematically studied
by a time-dependent density functional theory approach. The calculations revealed
that the absorption spectrum becomes significantly broad with increasing cluster
size, stretching from ultraviolet to the infrared region. The absorption spectra
are closely related to the structural motifs. With increasing cluster size, the
absorption intensity of cage structures gradually increases, but the absorption
curves of the prolate and the Y-shaped structures are very sensitive to cluster
size. If the transition energy reaches ~12 eV, it is noted that all the clusters
have remarkable absorption in deep ultraviolet region of 100-200 nm, and the
maximum absorption intensity is ~100 times that in the visible region. Further,
the optical responses to doping in the Si clusters were studied.
PMID- 28686440
TI - Temperature Effect on Rheological Behavior of Silicone Oils. A Model for the
Viscous Heating.
AB - The rheological behavior of silicone oils, (CH3)3SiO-[Si(CH3)2O]n-Si(CH3)3, and
their mixtures is studied. Shear-stress measurements, in the temperature range of
293-313 K, reveal that this polymer family is a group of shear-thinning liquids
with a yield stress below which no flow occurs. Experimental diagrams, i.e.,
shear stress versus shear rate, are satisfactorily described by the Casson fluid
model over a wide range of shear rates. In order to monitor the effect of
temperature on fluid properties, Casson's rheological model is reformulated using
the fictitious shear rate, gammaf, and the infinite-shear viscosity, etainfinity,
as constitutive parameters. Due to low intermolecular forces and high chain
flexibility, gammaf varies very little when the temperature increases. For this
reason, the apparent material viscosity depends on temperature only through
etainfinity, which exponentially decreases until high shear rates are reached,
and there is more alignment possible. Interestingly, the temperature sensitivity
of this pseudoplastic behavior is the same for all of the silicone oils
investigated; therefore, they can be classified according to their tendency to
emulsify. Experimental results are then used to model the flow of silicone oils
in a cylindrical pipe and estimate the temperature increase due to viscous
heating. Numerical results show that the normalized temperature, i.e., ratio of
fluid temperature to wall temperature, increases approximately 23%, and the
apparent viscosity decreases drastically, going toward the center of the tube.
The non-Newtonian nature of fluid is reflected in the presence of a critical
region. In this region, the velocity and temperature gradients vanish. Since
silicon oil is a surgical tool, we hope that the acquired physicochemical
information can provide help to facilitate the removal of this material during
surgical procedures.
PMID- 28686441
TI - A Direct Alcohol Fuel Cell Driven by an Outer Sphere Positive Electrode.
AB - Molecular oxygen, the conventional electron acceptor in fuel cells poses
challenges specific to direct alcohol fuel cells (DAFCs). Due to the coupling of
alcohol dehydrogenation with the scission of oxygen on the positive electrode
during the alcohol crossover, the benchmark Pt-based air cathode experiences
severe competition and depolarization losses. The necessity of heavy precious
metal loading with domains for alcohol tolerance in the state of the art DAFC
cathode is a direct consequence of this. Although efforts are dedicated to
selectively cleave oxygen, the root of the problem being the inner sphere nature
of either half-cell chemistry is often overlooked. Using an outer sphere electron
acceptor that does not form a bond with the cathode during redox energy
transformation, we effectively decoupled the interfacial chemistry from parasitic
chemistry leading to a DAFC driven by alcohol passive carbon nanoparticles, with
performance metrics ~8 times higher than Pt-based DAFC-O2.
PMID- 28686442
TI - Accuracy of Frequencies Obtained with the Aid of Explicitly Correlated Wave
Function Based Methods.
AB - We asses the basis set convergence of harmonic frequencies using different
explicitly correlated wave function based methods. All commonly available CCSD(T)
variants as well as MP2-F12 and MP4(F12*) are considered, and a hierarchy of the
different approaches is established. As for reaction and atomization energies,
CCSD(F12*)(T*) is a close approximation to CCSD(F12)(T*) and clearly superior to
the other tested approximations. The used scaling for the triples correction
enhances the accuracy relative to CCSD(F12*)(T) especially for small basis sets
and is very attractive since no additional computational costs are added.
However, this scaling slightly breaks size consistency, and therefore we
additionally study the accuracy of CCSD(F12*)(T*) and CCSD(F12*)(T) in the
context of calculating anharmonic frequencies to check if this causes problems in
the generation of the potential energy surface (PES). We find a fast basis set
convergence for harmonic and anharmonic frequencies. Already in the cc-pVDZ-F12
basis, the RMSD to the CBS limit is only around 4-5 cm-1.
PMID- 28686443
TI - Identification of Peptidic Antagonists of Vascular Endothelial Growth Factor
Receptor 1 by Scanning the Binding Epitopes of Its Ligands.
AB - Cancer angiogenesis is mainly initiated by vascular endothelial growth factors
(VEGFs). On the basis of the reported crystal structures of three natural ligands
(VEGF-A, -B, and PlGF) with the major receptors VEGFR-1 and VEGFR-2, we scanned
receptor-binding epitopes of these ligands by designing linear and cyclic
peptides with the aim to disrupt the VEGF-A/VEGFR-1 interaction, which is
implicated in cancer development. The ability of peptides to inhibit this
interaction was evaluated by an ELISA-based assay. Several peptides, especially
those mimicking loop 1 (L1) of these ligands that binds primarily to domain D3 of
VEGFRs, have demonstrated higher inhibition for VEGF-A/VEGFR-1 binding. They have
also shown inhibitory effects on VEGF-induced tube formation in HUVECs (human
umbilical vein endothelial cells). These results validate the domain D3 of VEGFRs
as an efficient target for the design of VEGFR antagonists.
PMID- 28686444
TI - Solvolytic Behavior of Aryl and Alkyl Carbonates. Impact of the Intrinsic Barrier
on Relative Reactivities of Leaving Groups.
AB - The effect of negative hyperconjugation on the solvolytic behavior of carbonate
diesters has been investigated kinetically by applying the LFER equation log k =
sf(Ef + Nf). The observation that carbonate diesters solvolyze faster than the
corresponding carboxylates and that the enhancement of aromatic carbonates is
more pronounced indicates that the negative hyperconjugation and pi-resonance
within the carboxylate moiety is operative in TS. The plots of DeltaG? vs
approximated DeltarG degrees for solvolysis of benzhydryl aryl/alkyl carbonates
and benzhydryl carboxylates reveal that a given carbonate solvolyzes over the
higher Marcus intrinsic barrier and over the earlier transition state than
carboxylate that produces an anion of similar stability. Due to the lag in
development of the electronic effects along the reaction coordinate, the impact
of the intrinsic barrier on solvolytic behavior of carbonates is more important
than in the case of carboxylates and phenolates. Consequently, the solvolytic
reaction constants (sf) are generally lower for carbonates than for carboxylates.
Because of considerable lower reaction constants of carbonates, an inversion of
relative reactivities between aryl/alkyl carbonate and another leaving group of
similar nucleofugality (Nf) may occur if the electrofuge moiety of a substrate is
switched.
PMID- 28686445
TI - Discovery and Optimization of Chromeno[2,3-c]pyrrol-9(2H)-ones as Novel Selective
and Orally Bioavailable Phosphodiesterase 5 Inhibitors for the Treatment of
Pulmonary Arterial Hypertension.
AB - Phosphodiesterase 5 (PDE5) inhibitors have been used as clinical agents to treat
erectile dysfunction and pulmonary arterial hypertension (PAH). Herein, we detail
the discovery of a novel series of chromeno[2,3-c]pyrrol-9(2H)-one derivatives as
selective and orally bioavailable inhibitors against phosphodiesterase 5.
Medicinal chemistry optimization resulted in 2, which exhibits a desirable
inhibitory potency of 5.6 nM with remarkable selectivity as well as excellent
pharmacokinetic properties and an oral bioavailability of 63.4%. In addition,
oral administration of 2 at a dose of 5.0 mg/kg caused better pharmacodynamics
effects on both mPAP (mean pulmonary artery pressure) and RVHI (index of right
ventricle hypertrophy) than sildenafil citrate at a dose of 10.0 mg/kg. These
activities along with its reasonable druglike properties, such as human liver
microsomal stability, cytochrome inhibition, hERG inhibition, and pharmacological
safety, indicate that 2 is a potential candidate for the treatment of PAH.
PMID- 28686446
TI - Theoretical Insights on Solvent Control of Intramolecular and Intermolecular
Proton Transfer of 2-(2'-Hydroxyphenyl)benzimidazole.
AB - Excited-state proton transfer (ESPT) processes of 2-(2'
hydroxyphenyl)benzimidazole (HBI) and its complexation with protic solvents (H2O,
CH3OH, and NH3) have been investigated by both static calculations and dynamics
simulations using density functional theory (DFT) at B3LYP/TZVP theoretical level
for ground state (S0) and time-dependent (TD)-DFT at TD-B3LYP/TZVP for excited
state (S1). For static calculations, absorption and emission spectra, infrared
(IR) vibrational spectra of O-H mode, frontier molecular orbitals (MOs), and
potential energy curves (PECs) of proton transfer coordinate were analyzed.
Simulated absorption and emission spectra show an agreement with available
experimental data. The hydrogen bond strengthening in the S1 state has been
proved by the changes of IR vibrational spectra and bond parameters of the
hydrogen moiety with those of the S0 state. The MOs provide the visual electron
density redistribution confirming the hydrogen bond strengthening mechanism. The
PECs show that the proton transfer (PT) process is easier to occur in the S1
state than the S0 state. Moreover, on-the-fly dynamics simulations of all systems
were carried out to provide the detailed information on time revolution. The
results revealed that the excited-state intermolecular proton transfer for HBI is
fast, whereas the excited-state intermolecular proton transfer for HBI with
protic solvents are slower than that of HBI because the competition between intra
and intermolecular hydrogen-bonds between HBI and protic solvent. These
intermolecular hydrogen-bonds hinder the formation of tautomer, hence explaining
the low quantum yield found in the protic solvent experiment. Especially for HBI
complexing with methanol, only ESIntraPT occurs with small probability compared
to HBI with water and ammonia.
PMID- 28686447
TI - Reduction of Electrolyte Components on a Coated Si Anode of Lithium-Ion
Batteries.
AB - Surface modification of Si anodes in Li-ion batteries by deposition of a thin
alucone coating has demonstrated an effective way to help maintain a stable
anode/electrolyte interface and good battery performance. In this work, we
investigate the interactions and reactivity of the film with electrolyte
components using ab initio molecular dynamics simulations. Adsorption of solvent
molecules (ethylene carbonate, EC) and salt (LiPF6) and reduction by two
mechanisms depending on the Li content of the film (yielding open EC adsorbed on
the film or C2H4 + CO32-) take place near the film/electrolyte and film/anode
interfaces. Reaction products incorporate into the structure of the film and
create a new kind of solid-electrolyte interphase layer.
PMID- 28686448
TI - Comparison between Seed and Foliar Treatment as a Tool in Integrated Pest
Management.
AB - A study into doses of seed treatments and foliar plant protection products
containing an identical active substance registered to control the same pest in
the same crops was carried out in the European Union. The results show that, for
fungicides, the use of seed treatment is often connected with a significantly
lower release of active substance per hectare when compared to foliar treatments.
In 11 of 13 cases, the difference was 8-fold or higher. For insecticides, in most
of the cases, the consumption of an active substance was several times higher for
seed treatment, in one case for foliar application.
PMID- 28686449
TI - Multicomponent Density Functional Theory: Impact of Nuclear Quantum Effects on
Proton Affinities and Geometries.
AB - Nuclear quantum effects such as zero point energy play a critical role in
computational chemistry and often are included as energetic corrections following
geometry optimizations. The nuclear-electronic orbital (NEO) multicomponent
density functional theory (DFT) method treats select nuclei, typically protons,
quantum mechanically on the same level as the electrons. Electron-proton
correlation is highly significant, and inadequate treatments lead to highly
overlocalized nuclear densities. A recently developed electron-proton correlation
functional, epc17, has been shown to provide accurate nuclear densities for
molecular systems. Herein, the NEO-DFT/epc17 method is used to compute the proton
affinities for a set of molecules and to examine the role of nuclear quantum
effects on the equilibrium geometry of FHF-. The agreement of the computed
results with experimental and benchmark values demonstrates the promise of this
approach for including nuclear quantum effects in calculations of proton
affinities, pKa's, optimized geometries, and reaction paths.
PMID- 28686450
TI - Complex Formations between Surfactants and Polyelectrolytes of the Same Charge on
a Water Surface.
AB - The mechanism of complex formation between surfactants and polyelectrolytes with
the same charge on the water surface was investigated using molecular dynamics
simulations and phase-sensitive sum-frequency generation vibrational
spectroscopy. Although complex formation between highly charged surfactants and
polyelectrolytes of the same charge is generally expected to be prohibited by the
electrostatic repulsive force, our study shows that it is possible to form
thermodynamically stable complexes when excess ions are present in the solution.
We found that anionic partially hydrolyzed polyacrylamide (HPAM) could interact
with anionic sodium dodecyl sulfate (SDS) on a water surface in the presence of
salts. With excess Na+ ions in the solution, the charge screening effect allows
HPAM to weakly interact with SDS via hydrogen bonds. In the presence of divalent
Ca2+ ions, the surfactant and the polymer are strongly coupled by forming Ca2+
ion bridges and hydrogen bonds. Our calculation shows that the presence of Ca2+
ions creates a steep binding energy of ~30 kJ/mol near the water surface. These
results were qualitatively verified using phase-sensitive sum-frequency
generation vibrational spectroscopy.
PMID- 28686451
TI - Revival of the Intermolecular Nuclear Overhauser Effect for Mapping Local Protein
Hydration Dynamics.
AB - The highly heterogeneous hydration dynamics of protein-water interfaces is
considered important for protein stability and dynamics, protein folding,
enzymatic activity, and even drug design. The nuclear Overhauser effect (NOE)
between protein and water protons is the only experimental observable which, in
principle, can provide a map of locally resolved hydration dynamics. However, its
utility was questioned in various theoretical studies that emphasized the
contributions of long-range NOE interactions. We show by a detailed analysis
based on molecular dynamics simulations that, contrary to recent claims, the
protein-water NOE is an excellent observable to map local hydration dynamics at
the protein surface.
PMID- 28686452
TI - Immunostimulatory Properties of Lipid Modified CpG Oligonucleotides.
AB - Innate immune responses recognizing pathogen associated molecular patterns play
important roles in adaptive immunity. As such, ligands which mimic the conserved
products of microbial and activate innate immunity are widely used as adjuvants
for vaccines. Synthetic single strand oligodeoxynucleotides (ODNs) containing
unmethylated cytosine-guanine (CpG) motifs which bind Toll-like receptor 9 (TLR9)
are powerful molecular adjuvants, potentiating both humoral and cellular
responses. However, CpG ODN's in vitro potency has not been translated to in vivo
settings primarily due to issues associated with delivery and toxicity. A major
challenge in clinical application of CpG ODN is the efficient delivery to lymph
nodes, the anatomic sites where all the immune responses are initiated. Targeting
CpG to the key antigen presenting cells (APC) is essential for its application as
a vaccine adjuvant, as it not only enhances CpG's efficacy, but also greatly
reduces the systemic toxicity. We recently discovered an "albumin-hitchhiking"
approach by which CpG ODNs were conjugated to a lipophilic lipid tail and follow
subcutaneous injection, accumulated in lymph nodes by binding and transporting
with endogenous albumin. This molecular approach targets CpG to antigen
presenting cells in the draining lymph nodes via an endogenous albumin-mediated
mechanism and simultaneously improves both the efficacy and safety of CpG as a
vaccine adjuvant. Since CpG ODNs can be divided into structurally distinct
classes, and each class of CpG ODN activates different types of immune cells and
triggers different types of immunostimulatory activities, it is important to
thoroughly evaluate the efficacy of this "albumin-hitchhiking" strategy in each
class of CpG. Here we compare the immunostimulatory activities of three classes
of lipid conjugated CpG ODNs in vitro and in vivo. Three representative sequences
of lipid modified CpG ODNs were synthesized and their stimulatory effects as a
vaccine adjuvant were evaluated. Our results showed that in vitro, lipid modified
class A CpG exhibited enhanced stimulatory activities toward TLR transfected
reporter cells or bone-marrow derived dendritic cells, whereas lipid-modification
of class B or C CpG reduces the activation of TLR9 by 2-3 fold, as compared with
unmodified class B and class C CpG, respectively. However, in vivo
coadministration of ovalbumin (OVA) protein antigen mixed with lipid-conjugated
class B or C CpG ODNs, but not class A CpGs induced dramatically increased OVA
specific humoral and cytotoxic CD8+ T cells responses compared with OVA mixed
with unmodified CpGs. Further, lipid-modification greatly reduces the toxicity
associated with CpG by minimizing the systemic dissemination. Taken together,
these results demonstrated that amphiphilic modification of three classes of CpG
motifs differentially affected and modulated the immunostimulatory activities in
vitro and in vivo. Our study highlights the importance of in vivo lymph node
targeting of CpG ODNs in fulfilling their use as vaccine adjuvants, providing
implications for the rational design of molecular adjuvant for subunit vaccines.
PMID- 28686453
TI - Phosphate Ion Functionalization of Perovskite Surfaces for Enhanced Oxygen
Evolution Reaction.
AB - Recent findings revealed that surface oxygen can participate in the oxygen
evolution reaction (OER) for the most active catalysts, which eventually triggers
a new mechanism for which the deprotonation of surface intermediates limits the
OER activity. We propose in this work a "dual strategy" in which tuning the
electronic properties of the oxide, such as La1-xSrxCoO3-delta, can be
dissociated from the use of surface functionalization with phosphate ion groups
(Pi) that enhances the interfacial proton transfer. Results show that the Pi
functionalized La0.5Sr0.5CoO3-delta gives rise to a significant enhancement of
the OER activity when compared to La0.5Sr0.5CoO3-delta and LaCoO3. We further
demonstrate that the Pi surface functionalization selectivity enhances the
activity when the OER kinetics is limited by the proton transfer. Finally, this
work suggests that tuning the catalytic activity by such a "dual approach" may be
a new and largely unexplored avenue for the design of novel high-performance
catalysts.
PMID- 28686454
TI - Multiresponsive Nanogels for Targeted Anticancer Drug Delivery.
AB - Nanogels with a biomolecular coating (biocoating) were shown to be capable of
triggered delivery of anticancer drug Doxorubicin. The biocoating was formed
utilizing binding between glycogen and the tetra-functional lectin Concanavalin
A, which can be triggered to disassemble (and release) upon exposure to glucose
and changes in solution pH. We also show the nanogel's thermoresponsivity can be
used to accelerate Doxorubicin release. Moreover, we showed that transferrin
immobilized on the nanogel surface could accelerate nanogel uptake by cancer
cells. In these experiments, we showed that Doxorubicin was able to be released
to the nucleus of human liver cancer cell line (HepG2) within 3 h. Doxorubicin
loaded nanogels exhibit a strong growth inhibition ability toward HepG2. This
investigation showcases how nanogel design and chemistry can be tuned to achieve
useful biomedical applications.
PMID- 28686455
TI - Co-Catalyzed Cross-Coupling Reaction of Alkyl Fluorides with Alkyl Grignard
Reagents.
AB - The cross-coupling reaction of unactivated alkyl fluorides with alkyl Grignard
reagents by a CoCl2/LiI/1,3-pentadiene catalytic system is described. The present
reaction smoothly cleaved C-F bonds under mild conditions and achieved alkyl
alkyl cross-coupling even when sterically hindered tertiary alkyl Grignard
reagents were employed. Since alkyl fluorides are inert toward many reagents and
catalytic intermediates, the use of the present reaction enables a new multistep
synthetic route to construct carbon frameworks by combining conventional
transformations.
PMID- 28686456
TI - Nickel-Catalyzed Trifluoromethylselenolation of Aryl Halides Using the Readily
Available [Me4N][SeCF3] Salt.
AB - A convenient and efficient method for the construction of aryl trifluoromethyl
selenoethers from the corresponding aryl halides in the presence of Ni(COD)2 and
an appropriate ligand is reported. Various aryl iodides, bromides, and chlorides
were smoothly converted in this reaction by simply varying the ligand, which
afforded aryl and heteroaryl trifluoromethyl selenoethers in good to almost
quantitative yields. The reaction was also applicable to the synthesis of
druglike molecules. This work is the first report for trifluoromethylselenolation
of aryl chlorides. Advantages of the present Ni-catalyzed approach include mild
reaction conditions, good functional group tolerance, inexpensive reagents, easy
operation, and no use of additional additives. This protocol allows for a
straightforward and reliable access to trifluoromethyl selenides that are latent
screening candidates for new pharmaceuticals and agrochemicals.
PMID- 28686457
TI - Tracking Nanoelectrochemistry Using Individual Plasmonic Nanocavities.
AB - We study in real time the optical response of individual plasmonic nanoparticles
on a mirror, utilized as electrodes in an electrochemical cell when a voltage is
applied. In this geometry, Au nanoparticles are separated from a bulk Au film by
an ultrathin molecular spacer. The nanoscale plasmonic hotspot underneath the
nanoparticles locally reveals the modified charge on the Au surface and changes
in the polarizability of the molecular spacer. Dark-field and Raman spectroscopy
performed on the same nanoparticle show our ability to exploit isolated plasmonic
junctions to track the dynamics of nanoelectrochemistry. Enhancements in Raman
emission and blue-shifts at a negative potential show the ability to shift
electrons within the gap molecules.
PMID- 28686458
TI - Tri-Substituted Triazole-Enabled C-H Activation of Benzyl and Aryl Amines by Iron
Catalysis.
AB - The design of trisubstituted triazoles set the stage for proximity-induced iron
catalyzed C-H activation of benzyl and aryl amines with ample scope. Thereby, C-H
alkylations and C-H arylations proved viable with high levels of chemo and
positional selectivities by means of racemization-free iron catalysis with the
reusable triazole being removed in a traceless fashion.
PMID- 28686459
TI - Electrically Controlled Scattering in a Hybrid Dielectric-Plasmonic Nanoantenna.
AB - Electrically tunable devices in nanophotonics offer an exciting opportunity to
combine electrical and optical functions, opening up their applications in active
photonic devices. Silicon as a kind of high refractive index dielectric material
has shown comparable performances with plasmonic nanostructures in tailoring and
modulating the electromagnetic waves. However, there are few studies on
electrically tunable silicon nanoantennas. Here, for the first time we realize
the spectral tailoring of an individual silicon nanoparticle in the visible range
through changing the applied voltage. We observe that the plasmon-dielectric
hybrid resonant peaks experience blue shift and obvious intensity attenuation
with increasing the bias voltages from 0 to 1.5 V. A physical model has been
established to explain how the applied voltage influences the carrier
concentration and how carrier concentration modifies the permittivity of silicon
and then the final scattering spectra. Our findings pave a new approach to build
excellent tunable nanoantennas or other nanophotonics devices where the optical
responses can be purposely controlled by electrical signals.
PMID- 28686460
TI - Phosphorylation of Alkenyl and Aryl C-O Bonds via Photoredox/Nickel Dual
Catalysis.
AB - A phosphorylation of alkenyl and aryl C-O bonds at room temperature via
photoredox/nickel dual catalysis is reported. By starting from easily available
and inexpensive sulfonates, a variety of important alkenyl phosphonates and aryl
phosphine oxides are generated in moderate to excellent yields. This method
features mild reaction conditions, high selectivity, good functional group
tolerance, wide substrate scope, and easy scalability.
PMID- 28686461
TI - A large meta-analysis of the global prevalence rates of S. aureus and MRSA
contamination of milk.
AB - Past reports have indicated a high prevalence of milk contaminated with
Staphylococcus aureus (S. aureus) and methicillin-resistant Staphylococcus aureus
(MRSA), but the pooled prevalence rates of S. aureus and MRSA in pasteurized and
boiled cow's milk, raw cow's milk, and raw Caprinae milk (raw sheep's milk and
raw goat's milk) and across different periods, continents, economic conditions
and purchase locations remain inconsistent. We searched relevant articles
published in PubMed, EMBASE, and Web of Science before July 2016. The
Strengthening the Reporting of Observational Studies in Epidemiology (STROBE)
Statement was used to evaluate the quality of 93 included studies. We observed
that the pooled prevalence rates of S. aureus contamination in pasteurized and
boiled cow's milk, raw cow's milk, and raw Caprinae milk were 15.4% (95% CI, 6.1
27.5%), 33.5% (95% CI, 29.5-37.7%) and 25.8% (95% CI, 17.5-35.0%), respectively.
The pooled prevalence rates of MRSA contamination were 4.9% (95% CI, 0.0-15.7%),
2.3% (95% CI, 1.3-3.6%), and 1.1% (95% CI, 0.5-1.8%), respectively. The
prevalence of S. aureus contamination in raw cow's milk increased over time.
However, the pooled prevalence of raw cow's milk contaminated with S. aureus was
lowest in European studies. These findings give an indication of the consequence
of better milk regulation in Europe. High S. aureus prevalence rates in raw milk
collected from farms and processing companies pose a potential threat to
consumers. The implementation of good hygiene practices, appropriate health
knowledge, and food safety principles at the farm level, as well as the prudent
use of antibiotics in veterinary medicine and heat treatment before drinking, are
necessary to reduce the potential risk of S. aureus and MRSA contamination.
PMID- 28686462
TI - A Logic for Checking the Probabilistic Steady-State Properties of Reaction
Networks.
AB - Designing probabilistic reaction models and determining their stochastic kinetic
parameters are major issues in systems biology. To assist in the construction of
reaction network models, we introduce a logic that allows one to express
asymptotic properties about the steady-state stochastic dynamics of a reaction
network. Basically, the formulas can express properties on expectancies,
variances, and covariances. If a formula encoding for experimental observations
on the system is not satisfiable, then the reaction network model can be
rejected. We demonstrate that deciding the satisfiability of a formula is NP
hard, but we provide a decision method based on solving systems of polynomial
constraints. We illustrate our method on a toy example.
PMID- 28686463
TI - Evolution and Vaccination of Influenza Virus.
AB - In this study, we present an application paradigm in which an unsupervised
machine learning approach is applied to the high-dimensional influenza genetic
sequences to investigate whether vaccine is a driving force to the evolution of
influenza virus. We first used a visualization approach to visualize the
evolutionary paths of vaccine-controlled and non-vaccine-controlled influenza
viruses in a low-dimensional space. We then quantified the evolutionary
differences between their evolutionary trajectories through the use of within-
and between-scatter matrices computation to provide the statistical confidence to
support the visualization results. We used the influenza surface Hemagglutinin
(HA) gene for this study as the HA gene is the major target of the immune system.
The visualization is achieved without using any clustering methods or prior
information about the influenza sequences. Our results clearly showed that the
evolutionary trajectories between vaccine-controlled and non-vaccine-controlled
influenza viruses are different and vaccine as an evolution driving force cannot
be completely eliminated.
PMID- 28686464
TI - The Influence of Liquids on the Mechanical Properties of Allografts in Bone
Impaction Grafting.
AB - Allografts are used to compensate for bone defects resulting from revision
surgery, tumor surgery, and reconstructive bone surgery. Although it is well
known that the reduction of fat content of allografts increases mechanical
properties, the content of liquids with a known grain size distribution has not
been assessed so far. The aim of the study was to compare the mechanical
properties of dried allografts (DA) with allografts mixed with a saline solution
(ASS) and with allografts mixed with blood (AB) having a similar grain size
distribution. Fresh-frozen morselized bone chips were cleaned chemically, sieved,
and reassembled in specific portions with a known grain size distribution. A
uniaxial compression was used to assess the yield limit, initial density, density
at yield limit, and flowability of the three groups before and after compaction
with a fall hammer apparatus. No statistically significant difference could be
found for the yield limit between DA and ASS (p = 0.339) and between ASS and AB
(p = 0.554). DA showed a statistically significant higher yield limit than AB (p
= 0.022). Excluding the effect of the grain size distribution on the mechanical
properties, it was shown that allografts have a lower yield limit when lipids are
present. The liquid content of allografts seems to play an inferior role as no
statistically significant difference could be found between DA and ASS. It is
suggested, in accordance with other studies, to chemically clean allografts
before implantation to reduce the contamination risk and the fat content.
PMID- 28686465
TI - Characterization and Primary Functional Analysis of a Bamboo ZEP Gene from
Phyllostachys edulis.
AB - Zeaxanthin epoxidase (ZEP) plays important roles in plant response to various
environmental stresses by involving in abscisic acid (ABA) biosynthesis and
xanthophyll cycle. A full-length cDNA of PeZEP was isolated from moso bamboo
(Phyllostachys edulis), which comprised of a 138-bp 5'-untranslated region (UTR),
a 381-bp 3'-UTR, and a 2013-bp open reading frame (ORF) encoding a putative
protein of 670 amino acids. PeZEP was mainly expressed in leaf blades and leaf
sheaths, and less in roots and culms. The transcript level of PeZEP in bamboo
leaf was elevated with the increasing light intensity. PeZEP was significantly
upregulated in response to high light (HL: 1200 MUmol.m-2.s-1) and reached to a
higher level after 1 h treatment, and kept higher levels in the following hours.
Besides, PeZEP was upregulated under high temperature (42 degrees C), and
downregulated under low temperature (4 degrees C) and exogenous ABA treatment.
The expression vector of PeZEP driven by CaMV 35S was constructed and transformed
into Arabidopsis thaliana. The transgenic plants overexpressing PeZEP were
generated and subjected to drought stress for morphological and physiological
assays. Compared with Col-0, the transgenic plants demonstrated enhanced
tolerance to drought stress, which appeared later wilting and higher survival
rate. Moreover, higher value of Fv/Fm, higher activities of superoxide dismutase,
peroxidase, and catalase, and lower concentration of malondialdehyde were also
observed in transgenic plants. Transcript levels of AtP5CS and AtRD29b related to
drought stress were enhanced in transgenic plants. These results indicated that
PeZEP might play an important function in response to drought stress in bamboo.
PMID- 28686466
TI - Reducing Alignment Time Complexity of Ultra-Large Sets of Sequences.
AB - The alignment of three or more protein or nucleotide sequences is known as
Multiple Sequence Alignment problem. The complexity of this problem increases
exponentially with the number of sequences; therefore, many of the current
approaches published in the literature suffer a computational overhead when
thousands of sequences are required to be aligned. We introduce a new approach
for dealing with ultra-large sets of sequences. A two-level clustering method is
considered. The first level clusters the input sequences by using their
biological composition, that is, the number of positive, negative, polar,
special, and hydrophobic amino acids. In the second level, each cluster is
divided into different clusters according to their similarity. Then, each cluster
is aligned by using any method/aligner. After aligning the centroid sequences of
each second-level cluster, we extrapolate the new gaps to each cluster of
sequences to obtain the final alignment. We present a study on biological data
with up to ~100,000 sequences, showing that the proposed approach is able to
obtain accurate alignments in a reduced amount of time; for example, in >10,000
sequences datasets, it is able to reduce up to ~45 times the required runtime of
the well-known Kalign.
PMID- 28686467
TI - Diagnosis Prediction from Electronic Health Records Using the Binary Diagnosis
History Vector Representation.
AB - Large amounts of rich, heterogeneous information nowadays routinely collected by
healthcare providers across the world possess remarkable potential for the
extraction of novel medical data and the assessment of different practices in
real-world conditions. Specifically in this work, our goal is to use electronic
health records (EHRs) to predict progression patterns of future diagnoses of
ailments for a particular patient, given the patient's present diagnostic
history. Following the highly promising results of a recently proposed approach
that introduced the diagnosis history vector representation of a patient's
diagnostic record, we introduce a series of improvements to the model and conduct
thorough experiments that demonstrate its scalability, accuracy, and
practicability in the clinical context. We show that the model is able to capture
well the interaction between a large number of ailments that correspond to the
most frequent diagnoses, show how the original learning framework can be adapted
to increase its prediction specificity, and describe a principled, probabilistic
method for incorporating explicit, human clinical knowledge to overcome semantic
limitations of the raw EHR data.
PMID- 28686468
TI - The experiences of people with borderline personality disorder admitted to acute
psychiatric inpatient wards: a meta-synthesis.
AB - BACKGROUND: Acute psychiatric inpatient care is recommended for people with
borderline personality disorder (BPD) to manage a crisis. Qualitative research
exploring service user experience is valuable for the development of evidence
based treatment guidelines. AIM: To conduct a meta-synthesis of qualitative
research exploring the experiences of people with BPD on acute psychiatric
inpatient wards. METHODS: Literatures searches of five electronic databases. Data
were analysed using a three-stage theme identification process. RESULTS: Eight
primary studies and three first-hand accounts met the inclusion criteria. Four
overarching themes were found to explain the data: contact with staff and fellow
inpatients; staff attitudes and knowledge; admission as a refuge; and the
admission and discharge journey. CONCLUSIONS: Similar experiences of acute
psychiatric inpatient care were reported by people with BPD across the studies.
Opportunities to be listened to and to talk to staff and fellow inpatients, time
out from daily life and feelings of safety and control were perceived as positive
elements of inpatient care. Negative experiences were attributed to: a lack of
contact with staff, negative staff attitudes, staff's lack of knowledge about
BPD, coercive involuntary admission and poor discharge planning.
PMID- 28686469
TI - Dietary compounds as modulators of metals and metalloids toxicity.
AB - A large part of the population is exposed to metals and metalloids through the
diet. Most of the in vivo studies on its toxicokinetics and toxicity are
conducted by means of exposure through drinking water or by intragastric or
intraperitoneal administration of aqueous standards, and therefore they do not
consider the effect of the food matrix on the exposure. Numerous studies show
that some components of the diet can modulate the toxicity of these food
contaminants, reducing their effect on a systemic level. Part of this protective
role may be due to a reduction of intestinal absorption and subsequent tissue
accumulation of the toxic element, although it may also be a consequence of their
ability to counteract the toxicity directly by their antioxidant and/or anti
inflammatory activity, among other factors. The present review provides a
compilation of existing information about the effect that certain components of
the diet have on the toxicokinetics and toxicity of the metals and metalloids of
greatest toxicological importance that are present in food (arsenic, cadmium,
lead, and mercury), and of their most toxic chemical species.
PMID- 28686470
TI - Sensory analysis and aroma compounds of buckwheat containing products-a review.
AB - Buckwheat is a rich source of starch, proteins, minerals and antioxidants, and as
such has become a popular functional ingredient incorporated in diverse
recipes/products with particular use in the gluten free market. Due to the
absence of gluten, application of buckwheat or buckwheat derived ingredients in
this particular food sector has increased significantly over recent years with
many buckwheat-based products appearing globally. Sensory analysis is an integral
part of the development of products that fulfill consumer expectations.
Therefore, investigations on the incorporation of health promoting functional
ingredients such as buckwheat into traditional recipes are often complemented by
the evaluation of appearance, aroma, taste and texture as well as overall quality
through standardized procedures involving trained judges or consumer panels.
Aroma is of particular importance in driving consumer preference and its sensory
assessment is often complemented with analytical workflows aiming to isolate and
determine the concentration of volatile compounds in food and understand the
effect of food components on the overall aroma intensity and/or perception of the
final product. The present manuscript provides a review of recent advances and
knowledge on the sensory characteristics, consumer preference and volatile
compound analysis of buckwheat and buckwheat based products.
PMID- 28686471
TI - The Meaning of "Breastfeeding" Is Changing and So Must Our Language About It.
AB - For millennia, the word "breastfeeding" has meant feeding an infant at his/her
own mother's breast. With the recent introduction of high-efficiency breast
pumps, other possibilities are now widely used, including feeding an infant
his/her own mother's milk from a cup or bottle. This milk may be recently pumped
or stored for a short or long time. Infants also may be fed another mother's
milk. As a result, the use of the term "breastfeeding" to describe these
different behaviors now inhibits clear communication among and between healthcare
providers, researchers, mothers, and members of the lay public. We propose a
comprehensive set of terms to describe these and related behaviors. Adoption and
consistent use of these terms would facilitate communication among all interested
parties on the topic of maternal lactation and infant feeding.
PMID- 28686472
TI - Children's Urinary Environmental Carbon Load. A Novel Marker Reflecting
Residential Ambient Air Pollution Exposure?
AB - RATIONALE: Ambient air pollution, including black carbon, entails a serious
public health risk because of its carcinogenic potential and as climate
pollutant. To date, an internal exposure marker for black carbon particles that
have cleared from the systemic circulation into the urine does not exist.
OBJECTIVES: To develop and validate a novel method to measure black carbon
particles in a label-free way in urine. METHODS: We detected urinary carbon load
in 289 children (aged 9-12 yr) using white-light generation under femtosecond
pulsed laser illumination. Children's residential black carbon concentrations
were estimated based on a high-resolution spatial temporal interpolation method.
MEASUREMENTS AND MAIN RESULTS: We were able to detect urinary black carbon in all
children, with an overall average (SD) of 98.2 * 105 (29.8 * 105) particles/ml.
The urinary black carbon load was positively associated with medium-term to
chronic (1 mo or more) residential black carbon exposure: +5.33 * 105
particles/ml higher carbon load (95% confidence interval, 1.56 * 105 to 9.10 *
105 particles/ml) for an interquartile range increment in annual residential
black carbon exposure. Consistently, children who lived closer to a major road
(<=160 m) had higher urinary black carbon load (6.93 * 105 particles/ml; 95%
confidence interval, 0.77 * 105 to 13.1 * 105). CONCLUSIONS: Urinary black carbon
mirrors the accumulation of medium-term to chronic exposure to combustion-related
air pollution. This specific biomarker reflects internal systemic black carbon
particles cleared from the circulation into the urine, allowing investigators to
unravel the complexity of particulate-related health effects.
PMID- 28686473
TI - Improving outcomes for homeless people with alcohol disorders: a multi-program
community-based approach.
AB - BACKGROUND: Relatively few community-based programs have been found to be helpful
for homeless people with alcohol disorders, even though this group represents a
high-risk, vulnerable population prone to poor outcomes. AIMS: This study sought
to implement and evaluate intensive community-based programs for homeless people
with alcohol disorders. METHOD: The project worked closely with a homeless
outreach team for referrals, and then provided two different, intensive substance
abuse treatment approaches matched to the needs of two subgroups: homeless
individuals with alcohol disorders without severe mental illness received
community reinforcement approach (CRA) and case management services, while those
with alcohol and severe mental illness were assigned to assertive community
treatment and integrated dual disorders (ACT/IDDT) services. The study enrolled
322 homeless people with alcohol disorders and outcomes were assessed at six
months and program discharge. RESULTS: Participants improved significantly over
the first six months in a number of outcome areas, including substance abuse,
mental health, housing, employment and health; progress generally remained stable
between six months and discharge. CONCLUSIONS: Community-based programs that
coordinate with mobile outreach teams and then provide CRA and ACT/IDDT appear to
be promising approaches for helping individuals with alcohol disorders out of
homelessness and into recovery.
PMID- 28686475
TI - Integration of the social environment in a mobility ontology for people with
motor disabilities.
AB - BACKGROUND: Our contemporary understanding of disability is rooted in the idea
that disability is the product of human-environment interaction processes. People
may be functionally limited, but this becomes a disability only when they engage
with their immediate social and physical environments. Any attempt to address
issues of mobility in relation to people with disabilities should be grounded in
an ontology that encompasses this understanding. PURPOSE: The objective of this
study is to provide a methodology to integrate the social and physical
environments in the development of a mobility ontology for people with motor
disabilities (PWMD). METHODS: We propose to create subclasses of concepts based
on a Nature-Development distinction rather than creating separate social and
physical subclasses. This allows the relationships between social and physical
elements to be modelled in a more compact and efficient way by specifying them
locally within each entity, and better accommodates the complexities of the human
environment interaction as well. Based on this approach, an ontology for mobility
of PWMD considering four main elements - the social and physical environmental
factors, human factors, life habits related to mobility and possible goals of
mobility - is presented. CONCLUSIONS: We demonstrate that employing the Nature
Development perspective facilitates the process of developing useful ontologies,
especially for defining the relationships between the social and physical parts
of the environment. This is a fundamental issue for modelling the interaction
between humans and their social and physical environments for a broad range of
applications, including the development of geospatial assistive technologies for
navigation of PWMD. Implications for rehabilitation The proposed perspective may
actually have much broader interests beyond the issue of disability - much of the
interesting dynamics in city development arises from the interaction between
human-developed components - the built environment and its associated entities -
and natural or organic components. The proposed approach facilitates the process
of developing useful ontologies, especially for defining the relationships
between the social and physical parts of the environment. This is a fundamental
issue for modeling the interaction between human -specially people with
disabilities -and his social and physical environments in a broad range of
domains and applications, such as Geographic Information Systems and the
development of geospatial assistive technologies for navigation of people with
disabilities, respectively.
PMID- 28686474
TI - Randomized, Double-Blind, Placebo-Controlled Trial Demonstrates the Efficacy and
Safety of Oral Aripiprazole for the Treatment of Tourette's Disorder in Children
and Adolescents.
AB - OBJECTIVES: Aripiprazole modulates dopaminergic and serotonergic pathways that
may play a role in the pathogenesis of Tourette's disorder (TD). This trial
evaluated the efficacy and safety of oral aripiprazole in the suppression of tics
in children and adolescents with TD. METHODS: This phase 3, randomized, double
blind, placebo-controlled trial ( ClinicalTrials.gov , NCT01727700) recruited
patients who were 7-17 years old with a diagnosis of TD from hospitals, private
practices, and research clinics at 76 sites in the United States, Canada,
Hungary, and Italy. Patients were randomized in a 1:1:1 ratio by using an
interactive voice/web-response system to low-dose aripiprazole (5 mg/day if <50
kg; 10 mg/day if >=50 kg), high-dose aripiprazole (10 mg/day if <50 kg; 20 mg/day
if >=50 kg), or placebo for 8 weeks. Randomization was stratified by region
(North America or Europe) and baseline body weight (<50 kg vs. >=50 kg). The
primary efficacy endpoint was mean change from baseline to week 8 in the Yale
Global Tic Severity Scale Total Tic Score (YGTSS-TTS) for the intent-to-treat
population. RESULTS: Between November 2012 and May 2013, 133 patients were
recruited and randomized to low-dose aripiprazole (n = 44), high-dose
aripiprazole (n = 45), or placebo (n = 44). Least-squares mean treatment
differences versus placebo in change from baseline to week 8 in the YGTSS-TTS
were statistically significant (high dose, -9.9 [95% confidence interval, CI,
13.8 to -5.9], low dose, -6.3 [95% CI, -10.2 to -2.3]). At week 8, 69% (29/42) of
patients in the low-dose and 74% (26/35) of patients in the high-dose
aripiprazole groups demonstrated a Clinical Global Impression-Tourette's Syndrome
improvement score of 1 (very much improved) or 2 (much improved) compared with
38% (16/42) in the placebo group. The most common adverse events (AEs) were
sedation (low dose, 8/44 [18.2%], high dose, 4/45 [8.9%], placebo, 1/44 [2.3%]),
somnolence (low dose, 5/44 [11.4%], high dose, 7/45 [15.6%], placebo, 1/44
[2.3%]), and fatigue (low dose, 3/44 [6.8%], high dose, 7/45 [15.6%], placebo,
0). No serious AEs or deaths occurred. CONCLUSIONS: This study indicates that
oral aripiprazole is a safe and effective treatment for tics in children and
adolescents with TD.
PMID- 28686477
TI - The issue of "long-term" fit notes for depression in the UK: patient, GP and
general practice variation.
AB - BACKGROUND: Depression is an important cause of certified sickness absence in the
UK. It is not known what factors are associated with variation in length of
sickness certificates issued by the GP to the depressed patient. AIMS: The
purpose of the study was to identify patient, GP and practice factors associated
with the issue of a long-term (> 4 week) fit note for depression. METHODS: Sixty
eight UK general practices collected sickness certification data for 12 months.
RESULTS: Over 35% of 8127 fit notes issued to 3361 patients for depression were
classed as long-term (over four weeks in duration). Having previous fit notes for
depression, not having "may be fit" advice on the fit note, older patient age,
the patient living in a deprived neighbourhood and a higher practice deprivation
status were all significant predictors of a long-term fit note. Depression fit
notes issued by female GPs to female patients were less likely to be long-term.
Other GP factors were not significant predictors of a long-term depression note.
CONCLUSIONS: Reducing the number of long-term sickness certificates issued to
people with depression should be considered part of return-to work and job
retention strategies.
PMID- 28686476
TI - Oncology Physicians' Perspectives on Practices and Barriers to Fertility
Preservation and the Feasibility of a Prospective Study of Pregnancy After Breast
Cancer.
AB - PURPOSE: POSITIVE (Pregnancy Outcome and Safety of Interrupting Therapy for women
with endocrine responsIVE breast cancer) is a prospective clinical trial
assessing safety and pregnancy outcomes in premenopausal hormone receptor
positive breast cancer survivors (age <=42) who interrupt endocrine therapy (ET)
to attempt pregnancy. We sought to assess interest in this study and perspectives
on fertility preservation (FP) among United States medical oncologists who had
previously enrolled women at their institutions on select premenopausal endocrine
studies. METHODS: From August 2015 to December 2015, 301 investigators were
invited to complete a web-based survey on behalf of their institution. We
assessed FP practices and attitudes, barriers to discussing FP, and willingness
to open/enroll women on POSITIVE. RESULTS: Of 93 respondents (31%), most were
affiliated with an National Cancer Institute (NCI)-designated comprehensive
cancer center (44%). Almost all said they usually or always discussed the issue
of future fertility with patients (98%) and referred patients with fertility
questions to specialists (97%). Over half of respondents cited discomfort with
recommending women to stop ET, as well as perceived patient concern regarding ET
interruption, as factors seen as influencing POSITIVE enrollment; however, 84%
were willing to recommend trial participation for selected patients. CONCLUSIONS:
Most providers reported discussing fertility with their young patients,
indicating awareness of FP guidelines for cancer patients. While most oncologists
said that they would be willing to recommend POSITIVE, many also expressed
discomfort in endorsing women to stop ET temporarily, underscoring the need for
prospective data regarding the safety of ET interruption. High willingness to
recommend POSITIVE suggests the potential for successful accrual to this study,
which addresses a critical issue for young breast cancer survivors.
PMID- 28686478
TI - Impact of medical comorbidity in psychiatric inpatient length of stay.
AB - BACKGROUND: Medical comorbidity is associated with worse psychiatric outcomes,
reduced functioning and higher services use, including inpatient psychiatric
care. AIM: We explored the relation between medical comorbidity and length of
stay, adjusting for potential confounders. METHODS: We retrospectively analyzed
an administrative database comprising all inpatient admissions between 2005 and
2014 at the Department of Psychiatry and Mental Health at Vila Nova de
Gaia/Espinho Healthcare Center, Vila Nova de Gaia - Portugal. Psychiatric
diagnosis and medical comorbidity were coded according to single-level and multi
level classification schemes, respectively, as proposed by the Clinical
Classification Software. RESULTS: We included a total of 4613 psychiatric
inpatient admissions. The prevalence of medical comorbidity was 25.4% and it was
associated with an average increase of 3.5 days (p < 0.001) in length of stay,
comparing to patients without medical comorbidity. After adjusting for potential
confounders, such as age, sex and year of discharge, medical comorbidity was
associated with a 13% increase in length of stay. CONCLUSIONS: Medical
comorbidity has measurable effects in inpatient outcomes, such as the length of
stay and should be a major focus for intervention, in ambulatory care but also
during psychiatric hospitalization.
PMID- 28686479
TI - Outcome of nasopharyngeal carcinoma in Finland: A nationwide study.
AB - BACKGROUND: Nasopharyngeal carcinoma (NPC) is uncommon in western countries and
data on the outcome and histological presentation are scarce in nonendemic areas.
We report here the outcome on all patients with NPC treated in Finland between
1990 and 2009. MATERIAL AND METHODS: The Finnish Cancer Registry database was
used to identify the patients. Histopathological specimens and clinical records
were reviewed to confirm the histological subtypes, prognostic factors, treatment
techniques and outcome across different stage groups. RESULTS: Primary NPC was
identified in 207 patients and 42 (20%) had keratinizing squamous cell carcinoma
(SCC). The stage distribution was: I, 11%; II, 25%; III, 39%; IV, 25%. Of 191
patients treated with curative intent 85 (44%) received radiotherapy and 106
(56%) chemoradiotherapy. The five-year overall survival for all patients was 57%
and for stages I-IV 87%, 69%, 55% and 31%, respectively. The five-year disease
specific and overall survival of all patients treated between 1990 and 1999 were
58% and 49%, and those between 2000 and 2009 66% and 63%, respectively.
CONCLUSIONS: While survival rates are improving and comparable to other western
countries they remain inferior to those of endemic countries. This may reflect
the different biology of NPC in nonendemic areas, where keratinizing SCC is
common.
PMID- 28686481
TI - Mindful emotion: a short course in kindness.
PMID- 28686480
TI - Caerulomycin A suppresses the differentiation of naive T cells and alleviates the
symptoms of experimental autoimmune encephalomyelitis.
AB - Multiple sclerosis (MS) is a highly detrimental autoimmune disease of the central
nervous system. There is no cure for it but the treatment typically focuses on
subsiding severity and recurrence of the disease. Experimental autoimmune
encephalomyelitis (EAE) is an animal model of MS. It is characterized by frequent
relapses due to the generation of memory T cells. Caerulomycin A (CaeA) is known
to suppress the Th1 cells, Th2 cells, and Th17 cells. Interestingly, it enhances
the generation of regulatory T cells (Tregs). Th1 cells and Th17 cells are known
to aggravate EAE, whereas Tregs suppress the disease symptoms. Consequently, in
the current study we evaluated the influence of CaeA on EAE. Intriguingly, we
observed by whole body imaging that CaeA regressed the clinical symptoms of EAE.
Further, there was reduction in the pool of Th1 cells, Th17 cells, and CD8 T
cells. The mechanism involved in suppressing the EAE symptoms was due to the
inhibition in the generation of effector and central memory T cells and induction
of the expansion of Tregs. In essence, these findings implicate that CaeA may be
considered as a potent future immunosuppressive drug.
PMID- 28686483
TI - Elevated resting heart rate is associated with the severity of coronary artery
disease in non-treated patients who underwent coronary angiography: potential
role of lipoprotein subfractions.
AB - OBJECTIVE: To assess the association between resting heart rate (RHR) and
lipoprotein subfractions to provide potential evidence for the relationship
between RHR and severity of CAD. METHODS: A total of 1119 consecutive non-treated
subjects scheduled for coronary angiography were enrolled. High-density
lipoprotein (HDL) and low-density lipoprotein (LDL) separation were performed by
Lipoprint System. The link of RHR with lipoprotein subfractions was assessed.
RESULTS: Increased RHR was significantly associated with higher triglyceride,
total cholesterol, non-HDL-cholesterol, and apolipoprotein B (all p < .01).
Furthermore, data indicated that higher RHR was related to more severe CAD (all p
< .05). In the following linear regression models, we observed that higher RHR
(HRh bpm) was significantly associated with lower large HDL (beta = -0.073, p =
.024) and higher small LDL subfraction (beta = 0.103, p = .005) after adjusting
for potential confounders. CONCLUSIONS: Increased RHR was associated with more
severe CAD, which may be partly due to the significant relation to atherogenic
lipoprotein subfractions.
PMID- 28686484
TI - Nursing and medical students teaming up: Results of an interprofessional project.
AB - Health professions programmes are increasing the number of interprofessional
events in their curricula. Many of these programmes are grounded in case study or
simulation events in order to prepare students for eventual practice. We designed
an interprofessional education collaborative practice (IPECP) that provides
direct interprofessional practice experience while students are still in their
health profession programmes. In our programme, teams of senior baccalaureate
nursing and third-year medical students provided health coaching to patients in
need of chronic disease management. The purpose of the project and study was to
determine whether repeated exposure to opportunities for interprofessional
communication would lead to improvement in the individual and team communication
skills. Teams met with their assigned patients monthly to provide coaching and
had follow-up conversations with the patients between meetings. Faculty were
present at each meeting to review the healthcare and coaching plans, observe the
teams' interactions, and provide a debriefing after each meeting. Results
demonstrated that both individual and team communication skills significantly
increased over time. The IPECP project was successful in providing a context
where students could develop and improve upon key interprofessional communication
skills.
PMID- 28686482
TI - Outer membrane vesicles blebbing contributes to B. vulgatus mpk-mediated immune
response silencing.
AB - The Gram negative intestinal symbiont Bacteroides vulgatus mpk is able to prevent
from induction of colonic inflammation in Rag1-/- mice and promotes immune
balance in Il2-/- mice. These inflammation-silencing effects are associated with
B. vulgatus mpk-mediated induction of semi-mature dendritic cells, especially in
the colonic lamina propria (cLP). However the beneficial interaction of bacteria
with host immune cells is limited due to the existence of a large mucus layer
covering the intestinal epithelium. How can intestinal bacteria overcome this
physical barrier and contact the host immune system? One mechanism is the
production of outer membrane vesicles (OMVs) via ubiquitous blebbing of the outer
membrane. These proteoliposomes have the ability to traverse the mucus layer.
Hence, OMVs play an important role in immunomodulation and the maintenance of a
balanced gut microbiota. Here we demonstrate that the stimulation of bone marrow
derived dendritic cells (BMDCs) with isolated OMVs originated from B. vulgatus
mpk leads to the induction of a tolerant semi-mature phenotype. Thereby, microbe-
associated molecular patterns (MAMPs) delivered by OMVs are crucial for the
interaction and the resulting maturation of immune cells. Additional to the
binding to host TLR4, a yet unknown ligand to TLR2 is indispensable for the
conversion of immature BMDCs into a semi-mature state. Thus, crossing the
epithelial mucus layer and directly contact host cells, OMV mediate cross
tolerance via the transport of various Toll-like receptor antigens. These
features make OMVs to a key attribute of B. vulgatus mpk for a vigorous acellular
prevention and treatment of systemic diseases.
PMID- 28686485
TI - Impaired salivary gland activity in patients with autoimmune polyendocrine
syndrome type I.
AB - Autoimmune polyendocrine syndrome type I (APS-I) is a severe disease caused by
mutations in the autoimmune regulator (AIRE) gene. We hypothesized that salivary
gland dysfunction could be a possible unexplored component of these patients and
here aimed to investigate salivary and lachrymal symptoms in the Norwegian cohort
of APS-I patients (N = 41) and the aetiology behind it. Sicca symptoms and
possible corresponding underlying factors were assessed by subjective reports
combined with objective measures of saliva and tear flow, serological testing,
immune fluorescence microscopy, ultrasonography and searching for putative
autoantibodies in the salivary glands. In addition, defensin and anti-defensin
levels were analysed in patients and compared with healthy controls. Our results
indicate mild salivary and/or lachrymal gland dysfunction manifesting in low
saliva or tear flow in a total of 62% of APS-I patients. Serum IgG from 9 of 12
patients bound to targets in salivary gland biopsy slides, although the
specificity and pattern of binding varied. There was no reactivity against known
Sjogren-associated autoantigens in sera from APS-I patients using quantitative
methods, but 11% were ANA positive by immunofluorescence microscopy. We
identified several putative autoantigens in one patient, although none of these
were verified as APS-I specific. We conclude that impaired salivary gland
activity is part of the clinical picture of APS-I and our findings could indicate
an autoimmune aetiology. We further show that APS-I patients have an altered
antimicrobial signature in both sera and saliva, which requires further
investigations.
PMID- 28686486
TI - Exploring challenges in the patient's discharge process from the internal
medicine service: A qualitative study of patients' and providers' perceptions.
AB - In hospital-based medicine units, patients have a wide range of complex medical
conditions, requiring timely and accurate communication between multiple
interprofessional providers at the time of discharge. Limited work has
investigated the challenges in interprofessional collaboration and communication
during the patient discharge process. In this study, authors qualitatively
assessed the experiences of internal medicine providers and patients about roles,
challenges, and potential solutions in the discharge process, with a
phenomenological focus on the process of collaboration. Authors conducted
interviews with 87 providers and patients-41 providers in eight focus-groups, 39
providers in individual interviews, and seven individual patient interviews.
Provider roles included physicians, nurses, therapists, pharmacists, care
coordinators, and social workers. Interviews were audio-recorded and transcribed
verbatim, followed by iterative review of transcripts using qualitative coding
and content analysis. Participants identified several barriers related to
interprofessional collaboration during the discharge process, including systems
insufficiencies (e.g., medication reconciliation process, staffing challenges);
lack of understanding others' roles (e.g., unclear which provider should be
completing the discharge summary); information-communication breakdowns (e.g.,
inaccurate information communicated to the primary medical team); patient issues
(e.g., patient preferences misaligned with recommendations); and poor
collaboration processes (e.g., lack of structured interprofessional rounds).
These results provide context for targeting improvement in interprofessional
collaboration in medicine units during patient discharges. Implementing changes
in care delivery processes may increase potential for accurate and timely
coordination, thereby improving the quality of care transitions.
PMID- 28686487
TI - Nanoscale invaginations of the nuclear envelope: Shedding new light on wormholes
with elusive function.
AB - Recent advances in fluorescence microscopy have opened up new possibilities to
investigate chromosomal and nuclear 3D organization on the nanoscale. We here
discuss their potential for elucidating topographical details of the nuclear
lamina. Single molecule localization microscopy (SMLM) in combination with
immunostainings of lamina proteins readily reveals tube-like invaginations with a
diameter of 100-500 nm. Although these invaginations have been established as a
frequent and general feature of interphase nuclei across different cell types,
their formation mechanism and function have remained largely elusive. We
critically review the current state of research, propose possible connections to
lamina associated domains (LADs), and revisit the discussion about the potential
role of these invaginations for accelerating mRNA nuclear export. Illustrative
studies using 3D super-resolution imaging are shown and will be instrumental to
decipher the physiological role of these nanoscale invaginations.
PMID- 28686488
TI - Contribution of both B-cell intrinsic alterations as well as non-hematopoietic
derived factors in the enhanced immune response of the NOD mouse.
AB - The underlying cellular and molecular mechanism for the development of Type 1
diabetes is still to be fully revealed. We have previously demonstrated that the
NOD mouse, a model for Type 1 diabetes, display a prolonged and enhanced immune
response to both self and non-self-antigens. The molecular explanation for this
defect however, has not been determined. In this study we immunized NOD and
C57BL/6 (B6) with the conventional antigen i.e. hen egg lysozyme (HEL) and
analyzed B cell activation, germinal center reaction and antibody clearance.
Corroborating our previous observations NOD mice responded robustly to a single
immunization of HEL. Immunofluorescence analysis of the spleen revealed an
increased number of germinal centers in unimmunized NOD compared to B6. However,
post immunization germinal center numbers were similar in NOD and B6. NOD mice
showed lower response to BCR stimulation with anti-IgM, in particular at lower
concentrations of anti-IgM. Antibody clearance in vivo did not differ between the
strains. To determine the cell type that is responsible for the prolonged and
enhance immune response, we reconstituted NOD-RAGs with cells from primed donors
in different combinations. NOD B cells were required to reproduce the phenotype;
however the non-lymphoid compartment of NOD origin also played a role. Based on
our results we propose that preexisting GCs in the NOD promote the robust
response and alteration in the BCR signaling could promote survival of stimulated
cells. Overall, this mechanism could in turn also contribute to the activation
and maintenance of autoreactive B cells in the NOD mouse.
PMID- 28686489
TI - Adolescent Experiences of Clinician-Patient HIV/STI Communication in Primary
Care.
AB - Effective clinician-patient communication is linked to positive patient health
outcomes in adults, yet the research on adolescent populations remains limited.
We describe adolescent experiences of clinician-patient HIV/STI communication
through qualitative interviews with predominantly African-American adolescent
women from a youth-centered primary care clinic. Participants described
acknowledging clinicians are professionals, the importance of confidentiality to
foster clinician-adolescent communication, and calling for clinician-initiated
HIV/STI communication. Adolescents expressed the necessity for clinicians to
engage youth in these challenging conversations through an open and understanding
approach. Additionally, adolescents described experiences of perceived judgment
and uncomfortableness from clinicians, and non-disclosure of HIV/STI risk
behaviors to their clinician. Findings underscore the adolescents' desire to
engage in HIV/STI communication with healthcare providers, while highlighting
important strategies for clinicians. Results can inform health communication
research and practice, and the development of interventions aimed at increasing
clinician-adolescent HIV/STI communication.
PMID- 28686490
TI - Preliminary inter-rater reliability of the wheelchair components questionnaire
for condition.
AB - PURPOSE: The Wheelchair Components Questionnaire for Condition (WCQ-C) enables
the collection of data on wheelchair maintenance condition and durability in
resource-limited environments. It can be used in large studies to indicate
typical patterns of wear at a location, or for a type of wheelchair. It can also
be used in clinical settings as an evidence based indication that a wheelchair
may need repair or replacement. This type of data can enable effective use of
limited funds by wheelchair providers, manufacturers and users. The goal of this
study was to investigate the inter-rater reliability of the WCQ-C. METHODS: Two
therapists from North America who have worked extensively in low-resource areas
used the WCQ-C to independently evaluate 46 wheelchairs at a primary school for
children with disabilities in Kenya. RESULTS: Mean scores of ratings for each
wheelchair by the two raters were used to calculate a two-way random interclass
correlation coefficient. A value of 0.82 with a 95% confidence interval of 0.67
0.89 indicated good preliminary reliability. CONCLUSION: Preliminary results
indicate that the WCQ-C is a reliable method of assessment. Additional studies
are needed with larger and more diverse groups of raters. Because WCQ-C findings
are specific to wheelchair wear and maintenance at each location, studies at
other locations are also needed. Implications for rehabilitation The importance
of inter-rater reliability testing in confirming the reliability of an assessment
tool such as the WCQ-C. The use of the WCQ-C to monitor wheelchair condition in
low-resource settings and other field settings. If used at regular interval can
produce data that can be used to describe typical changes over time at each
individual setting. This could enable proactive planning at that setting to avoid
typical breakdowns and the injuries or clinical complications that could result.
The use of the WCQ-C to monitor the condition of groups of wheelchairs of the
same type. It can describe typical patterns of wear and failure in a way that
enables responsive change by manufacturers and designers. This enables more
effective use of limited funds. On an individual basis, the use of the WCQ-C to
alert users and health professionals of a need for repair or replacement. This
could minimize the clinical problems and accidents that can result from
wheelchair breakdown. Assessment of a wheelchair using the WCQ-C could provide
evidence based data to insurance companies or wheelchair providers which
indicates a need for wheelchair repair or replacement.
PMID- 28686491
TI - Falling through the cracks: the decline of mental health care and firearm
violence.
AB - BACKGROUND: This paper argues that the decline in the availability of long-term,
intensive mental health services, particularly through state mental health
hospital systems, has had negative impacts on firearm-related deaths and possibly
on the incidence of mass shooting events. AIMS: Establish the effect of reduced
availability of long-term, intensive mental health treatment on firearm-related
violence in the United States. METHOD: Ordinary least squares regressions on
cross-sectional data of US states. RESULTS: Mass shooting perpetrators had
significantly higher rates of mental illness than the general population. In
addition, using simple regressions, this paper's results demonstrate that
increasing the number of state psychiatric hospital beds is associated with lower
rates of homicide. CONCLUSIONS: The shrinking number of intensive, long-term
mental health facilities in US states has had many negative consequences,
including higher rates of firearm homicide.
PMID- 28686492
TI - Effect of Equilibrated pH and Indigenous Spoilage Microorganisms on the
Inhibition of Proteolytic Clostridium botulinum Toxin Production in Experimental
Meals under Temperature Abuse.
AB - Clostridium botulinum is a foreseeable biological hazard in prepared refrigerated
meals that needs to be addressed in food safety plans. The objective of this
study was to evaluate the effect of product composition and storage temperature
on the inhibition of botulinum toxin formation in nine experimental meals (meat,
vegetable, or carbohydrate based). Treatments were inoculated with proteolytic C.
botulinum, vacuum packaged, cooked at 90 degrees C for 10 min, and assayed for
botulinum toxin in samples stored at 25 degrees C for up to 96 h for phase 1, or
at 25 degrees C for 12 h and then transferred to 12.5 degrees C for up to 12 and
6 weeks in phases 1 and 2, respectively. For phase 1, none of the treatments
(equilibrated pH 5.8) supported toxin production when stored at 25 degrees C for
48 h, but toxin production was observed in all treatments at 72 h. For the
remaining experiments with storage at 12.5 degrees C, toxin production was
dependent on equilibrated pH, storage time, and growth of indigenous spoilage
microorganisms. In phase 1, no gross spoilage and no botulinum toxin was detected
for any treatment (pH <=5.8) stored at 12.5 degrees C for 12 weeks. In phase 2,
gross spoilage varied by commodity, with the brussels sprouts meal with pH 6.5
showing the most rapid spoilage within 2 weeks and botulinum toxin detected at 5
and 6 weeks for the control and cultured celery juice treatments, respectively.
In contrast, spoilage microbes decreased the pH of a pH 5.9 beef treatment by 1.0
unit, potentially inhibiting C. botulinum through 6 weeks at 12.5 degrees C. None
of the other treatments with pH 5.8 or below supported toxin production or
spoilage. This study provides validation for preventive controls in refrigerated
meals. These include equilibrated product pH and storage temperature and time to
inhibit toxin formation by proteolytic C. botulinum, but the impact of indigenous
microflora on safety and interpretation of challenge studies is also highlighted.
PMID- 28686493
TI - Effect of Cultured Celery Juice, Temperature, and Product Composition on the
Inhibition of Proteolytic Clostridium botulinum Toxin Production.
AB - Clostridium botulinum may be of concern in prepared refrigerated meals, for which
strict cold chain management cannot be guaranteed. This study evaluated the
effect of temperature, product composition, and cultured celery juice powder
(CCJP) as a source of nitrite on the inhibition of botulinum toxin formation in
two experimental (meat- and vegetable-based) prepared meals. Data obtained from
the challenge study were compared with a published mathematical model to
determine whether the model is fail-safe with regard to the tested meals.
Treatments were inoculated with proteolytic C. botulinum, vacuum packaged, cooked
at 90 degrees C for 10 min, and assayed for botulinum toxin at appropriate
intervals in samples stored at 10, 15, or 20 degrees C for up to 8 weeks. None of
the treatments stored at 10 degrees C for 8 weeks supported toxin production by
proteolytic C. botulinum. The addition of CCJP delayed toxin production by 1 and
3 weeks in cauliflower potatoes and in Dijon pork, respectively, stored at 15
degrees C. Toxin production was delayed by 1 week at 20 degrees C when CCJP was
added to the cauliflower potatoes. This study found that the predictive model was
fail-safe but was overly conservative for the experimental meals described.
Finally, this study confirms that product composition, the addition of nitrite
via CCJP, storage time, and temperature play important roles in the inhibition of
toxin formation by proteolytic C. botulinum.
PMID- 28686494
TI - Antibodies to Various Zoonotic Pathogens Detected in Feral Swine (Sus scrofa) at
Abattoirs in Texas, USA.
AB - The zoonotic risk posed to employees by slaughtering feral swine (Sus scrofa) at
two abattoirs in Texas was assessed by testing feral swine serum samples for
exposure to influenza A virus, Leptospira, Trichinella spiralis, and Toxoplasma
gondii. Blood was collected from a total of 376 feral swine between the two
facilities during six separate collection periods in 2015. Antibodies to one or
more serovars of Leptospira were identified in 48.9% of feral swine tested, with
Bratislava and Pomona as the most commonly detected serovars, and antibodies to
influenza A virus were detected in 14.1% of feral swine. Antibodies to T. gondii
and T. spiralis were identified in 9.0 and 3.5%, respectively, of feral swine
tested. Our results suggest that abattoir employees should be aware of the
potential for exposure to various zoonotic pathogens when slaughtering feral
swine, wear appropriate personal protective equipment, and participate in medical
monitoring programs to ensure detection and prompt treatment. In addition,
consumers of feral swine should cook the meat to the appropriate temperature and
wash hands and kitchen surfaces thoroughly after preparing meat.
PMID- 28686495
TI - beta-Resorcylic Acid, a Phytophenolic Compound, Reduces Campylobacter jejuni in
Postharvest Poultry.
AB - Human Campylobacter infections, a leading foodborne illness globally, has been
linked with the high prevalence of this bacterium on raw retail chicken products.
Reduction of Campylobacter counts on poultry products would greatly reduce the
risk of subsequent infections in humans. To this end, this study investigated the
potential of the phytophenolic compound beta-resorcylic acid (BR) to reduce
Campylobacter counts on postharvest poultry (chicken skin or meat). Four trials
in total, two each on thigh skin or breast meat, were conducted in which chicken
skin or meat samples (2 +/- 0.1 g; 10 samples per treatment) were inoculated with
50 MUL (~106 CFU per sample) of a cocktail of four wild strains of C. jejuni.
After 30 min of attachment, inoculated samples were dipped in a 0, 0.5, 1, or 2%
BR solution for 30 s immediately followed by vigorously vortexing the samples in
Butterfield's phosphate diluent and plating the supernatant for Campylobacter
enumeration. In addition, the effect of BR on the color of skin and meat samples
was studied. Moreover, the change in the expression of survival and virulence
genes of C. jejuni exposed to BR was evaluated. Data were analyzed by the PROC
MIXED procedure of SAS (P < 0.05; SAS Institute Inc., Cary, NC). All BR
treatments significantly reduced Campylobacter populations on both chicken or
meat samples by 1 to 3 log CFU/g compared with non-BR-treated washed controls. No
significant difference in the lightness, redness, and yellowness of skin and meat
samples was observed on exposure to BR wash (P > 0.05). Real-time PCR results
revealed that BR treatment down-regulated expression of select genes coding for
motility (motA, motB) and attachment (cadF, ciaB) in the majority of C. jejuni
strains. Stress response genes (sodB, katA) were upregulated in C. jejuni S-8 (P
< 0.05). Overall, our results suggest that BR could be effectively used as
antimicrobial dip treatment during poultry processing for reducing Campylobacter
on chicken carcasses.
PMID- 28686496
TI - Polychlorinated Biphenyls and Polychlorinated Dioxins-Furans in Lake Trout and
Whitefish Composite Samples from Commercial Fisheries in Lakes Erie, Huron, and
Superior.
AB - Polychlorinated biphenyls (PCBs; sum of 36 congeners) and polychlorinated dibenzo
p-dioxins and dibenzofurans (PCDD/Fs; sum of 17 2,3,7,8-substituted congeners)
were measured in 93 composite samples prepared from individual lake trout
(Salvelinus namaycush) and whitefish (Coregonus clupeaformis) samples collected
from Lake Erie, Lake Huron, and Lake Superior. All samples had detectable
concentrations of PCBs and PCDD/Fs; maximum PCB concentrations in both trout (750
ng g-1 whole weight [ww]) and whitefish (210 ng g-1 ww) were found in composites
from fish collected from Lake Huron. The maximum toxic equivalent concentration
was found in a lake trout composite sample from Lake Huron (53 pg g-1 ww). PCB
and PCDD/F congener profiles were comparable to patterns observed in fishes
collected from other regions of Canada, although concentrations were above those
found in other regions. A positive correlation was found between PCB
concentrations determined using the historical Aroclor equivalency method and
those determined using the sum of the congeners measured (r2 = 0.871; Spearman
correlation r = 0.917) or using the six indicator PCB congeners (28, 52, 101,
138, 153, and 180; r2 = 0.850; Spearman correlation r = 0.935). PCBs were the
dominant contributor to the overall toxic equivalent concentrations in the fish
composite samples tested. These findings provide insight into PCB and PCDD/F
concentrations in two commercially important fish species over a discrete time
period.
PMID- 28686497
TI - Immunohistochemistry of Pulmonary Biomarkers: A Perspective From Members of the
Pulmonary Pathology Society.
AB - The use of immunohistochemistry for the determination of pulmonary carcinoma
biomarkers is a well-established and powerful technique. Immunohistochemisty is
readily available in pathology laboratories, is relatively easy to perform and
assess, can provide clinically meaningful results very quickly, and is relatively
inexpensive. Pulmonary predictive biomarkers provide results essential for timely
and accurate therapeutic decision making; for patients with metastatic non-small
cell lung cancer, predictive immunohistochemistry includes ALK and programmed
death ligand-1 (PD-L1) (ROS1, EGFR in Europe) testing. Handling along proper
methodologic lines is needed to ensure patients receive the most accurate and
representative test outcomes.
PMID- 28686498
TI - Perceptions of Unprofessional Attitudes and Behaviors: Implications for Faculty
Role Modeling and Teaching Professionalism During Pathology Residency.
AB - CONTEXT: - Changes occurring in medicine have raised issues about medical
professionalism. Professionalism is included in the Core Competencies and
Milestones for all pathology residents. Previous studies have looked at resident
professionalism attitudes and behaviors in primary care but none have looked
specifically at pathology. OBJECTIVE: - To examine behavior and attitudes toward
professionalism within pathology and to determine how professionalism is taught
in residency programs. DESIGN: - Surveys were sent to all College of American
Pathologists junior members and all pathology residency program directors, and
responses were compared. RESULTS: - Although no single behavior received the same
professionalism rating among residents and program directors, both groups
identified the same behaviors as being the most unprofessional: posting
identifiable patient information or case images to social media, making a
disparaging comment about a physician colleague or member of the support staff on
social media or in a public hospital space, and missing work without reporting
the time off. Faculty were observed displaying most of these behaviors as often
or more often than residents by both groups. The most common means to teach
professionalism in pathology residencies is providing feedback as situations
arise and teaching by example. Age differences were found within each group and
between groups for observed behaviors and attitudes. CONCLUSIONS: - As teaching
by example was identified as a common educational method, faculty must be aware
of the role their behavior and attitudes have in shaping resident behavior and
attitudes. These results suggest a need for additional resources to teach
professionalism during pathology residency.
PMID- 28686499
TI - Pathologists' Computer-Assisted Diagnosis: A Mock-up of a Prototype Information
System to Facilitate Automation of Pathology Sign-out.
AB - CONTEXT: - Pathologists' computer-assisted diagnosis (pCAD) is a proposed
framework for alleviating challenges through the automation of their routine sign
out work. Currently, hypothetical pCAD is based on a triad of advanced image
analysis, deep integration with heterogeneous information systems, and a concrete
understanding of traditional pathology workflow. Prototyping is an established
method for designing complex new computer systems such as pCAD. OBJECTIVE: - To
describe, in detail, a prototype of pCAD for the sign-out of a breast cancer
specimen. DESIGN: - Deidentified glass slides and data from breast cancer
specimens were used. Slides were digitized into whole-slide images with an Aperio
ScanScope XT, and screen captures were created by using vendor-provided software.
The advanced workflow prototype was constructed by using PowerPoint software.
RESULTS: - We modeled an interactive, computer-assisted workflow: pCAD previews
whole-slide images in the context of integrated, disparate data and predefined
diagnostic tasks and subtasks. Relevant regions of interest (ROIs) would be
automatically identified and triaged by the computer. A pathologist's sign-out
work would consist of an interactive review of important ROIs, driven by required
diagnostic tasks. The interactive session would generate a pathology report
automatically. CONCLUSIONS: - Using animations and real ROIs, the pCAD prototype
demonstrates the hypothetical sign-out in a stepwise fashion, illustrating
various interactions and explaining how steps can be automated. The file is
publicly available and should be widely compatible. This mock-up is intended to
spur discussion and to help usher in the next era of digitization for
pathologists by providing desperately needed and long-awaited automation.
PMID- 28686500
TI - Guidelines for Pathologic Diagnosis of Malignant Mesothelioma 2017 Update of the
Consensus Statement From the International Mesothelioma Interest Group.
AB - CONTEXT: - Malignant mesothelioma (MM) is an uncommon tumor that can be difficult
to diagnose. OBJECTIVE: - To provide updated, practical guidelines for the
pathologic diagnosis of MM. DATA SOURCES: - Pathologists involved in the
International Mesothelioma Interest Group and others with an interest and
expertise in the field contributed to this update. Reference material included up
to-date, peer-reviewed publications and textbooks. CONCLUSIONS: - There was
discussion and consensus opinion regarding guidelines for (1) distinguishing
benign from malignant mesothelial proliferations (both epithelioid and spindle
cell lesions), (2) cytologic diagnosis of MM, (3) recognition of the key
histologic features of pleural and peritoneal MM, (4) use of histochemical and
immunohistochemical stains in the diagnosis and differential diagnosis of MM, (5)
differentiating epithelioid MM from various carcinomas (lung, breast, ovarian,
and colonic adenocarcinomas, and squamous cell and renal cell carcinomas), (6)
diagnosis of sarcomatoid MM, (7) use of molecular markers in the diagnosis of MM,
(8) electron microscopy in the diagnosis of MM, and (9) some caveats and pitfalls
in the diagnosis of MM. Immunohistochemical panels are integral to the diagnosis
of MM, but the exact makeup of panels employed is dependent on the differential
diagnosis and on the antibodies available in a given laboratory. Depending on the
morphology, immunohistochemical panels should contain both positive and negative
markers for mesothelial differentiation and for lesions considered in the
differential diagnosis. Immunohistochemical markers should have either
sensitivity or specificity greater than 80% for the lesions in question.
Interpretation of positivity generally should take into account the localization
of the stain (eg, nuclear versus cytoplasmic) and the percentage of cells
staining (>10% is suggested for cytoplasmic and membranous markers). Selected
molecular markers are now being used to distinguish benign from malignant
mesothelial proliferations. These guidelines are meant to be a practical
diagnostic reference for the pathologist; however, some new pathologic predictors
of prognosis and response to therapy are also included.
PMID- 28686501
TI - Improved treatment decisions in patients with esophageal cancer.
AB - BACKGROUND: Patients with esophageal cancer seldom achieve long-term survival.
This prospective cohort study investigated the selection of patients likely to
benefit from curative treatment and whether information on patients' health
related quality of life (HRQL) would assist treatment decisions in the
multidisciplinary team. METHODS: Consecutive patients completed HRQL assessments
and clinical data were collected before start of treatment. Logistic regression
analyses identified clinical factors associated with treatment intent in patients
with stage-III disease. Kaplan-Meier method was used for survival analyses and
Cox proportional hazards models were used to assess the impact of clinical
factors and HRQL on survival in patients planned for curative treatment. RESULTS:
Patients with curative treatment intent (n = 90) were younger, had better WHO
performance status and less fatigue than patients with palliative treatment
intent (n = 89). Median survival for the total cohort (n = 179) and patients with
palliative or curative treatment intent was nine, five and 19 months,
respectively. In multivariate Cox regression analyses, performance status (0-1
favorable) and comorbidity (ASA I favorable) were factors of importance for
survival, whereas measures of HRQL were not. CONCLUSIONS: Patients performance
status and comorbidity must be considered in addition to stage of disease to
avoid extensive curative treatment in patients with short life expectancy. This
study did not provide evidence to support that information on patients HRQL adds
value to the multidisciplinary team's treatment decision process.
PMID- 28686502
TI - Recurrent Yeast Infections and Vulvodynia: Can We Believe Associations Based on
Self-Reported Data?
AB - OBJECTIVE: We determined whether self-reported new or recurrent yeast infections
were a risk factor for and/or consequence of vulvodynia and then determined the
extent to which various levels of misclassification of self-reported yeast
infections influenced these results. MATERIALS AND METHODS: In this case-control
study we retrospectively assessed self-reported new and recurrent yeast
infections prior and subsequent to first vulvar pain onset among 216 clinically
confirmed cases and during a similar time period for 224 general population
controls. RESULTS: A history of >10 yeast infections before vulvodynia onset was
strongly but imprecisely associated with currently diagnosed vulvodynia after
adjustment for age, age at first intercourse, and history of urinary tract
infections [adjusted odds ratio = 5.5, 95% confidence interval (CI) 1.7-17.8].
Likewise, a history of vulvodynia was associated with a twofold risk of
subsequent new or recurrent onset of yeast infections after adjustment for age,
age at first intercourse, and history of yeast infections before vulvodynia onset
(comparable time period among controls, 95% CI 1.5-2.9). Bias analyses showed
that our observed associations were an underestimation of the true association
when nondifferential misclassification of self-reported yeast infections and
certain differential misclassification scenarios were present. However, if women
with vulvodynia more frequently misreported having them when they truly did not,
our observed associations were an overestimate of the truth. CONCLUSIONS: There
appears to be a positive relationship between yeast infections preceding and
following the diagnosis of vulvodynia, but this relationship varies from strong
to nonexistent depending on the relative accuracy of the recalled diagnosis of
yeast infections among cases and controls. To better understand the bidirectional
associations between yeast infections and vulvodynia, future validation studies
are needed to determine the extent to which misclassification of self-reported
yeast infections differs between women with and without vulvodynia.
PMID- 28686503
TI - Characterization of Carbapenem-Resistant Escherichia coli Isolates Through the
Whole-Genome Sequencing Analysis.
AB - Limited studies have characterized multiple carbapenem-resistant Escherichia coli
isolates and compared their genetic characteristics through whole-genome
sequencing (WGS) because of the scarcity of these isolates. In this study, we
determined the prevalence of carbapenem resistance in 2,993 E. coli isolates
collected from three Chinese hospitals. The carbapenem-resistant isolates were
further characterized by WGS, and the molecular epidemiological characters and
resistance mechanisms were explored through the publicly available platforms from
the Center for Genomic Epidemiology. Twenty-four carbapenem-resistant E. coli
isolates were screened out from 2,993 E. coli clinical isolates and all
carbapenem-resistant isolates showed multiple drug-resistant phenotypes. The main
serotypes identified among carbapenem-resistant isolates through WGS included E.
coli O8:H21 (n = 6), E. coli O102:H6 (n = 6), and E. coli O25:H4 (n = 3), and the
dominant sequence types (ST) were ST410 (n = 8), ST405 (n = 6), and ST131 (n =
3). Carbapenemase encoding genes, including blaIMP-4 (n = 3), blaKPC-2 (n = 2),
blaNDM-5 (n = 1), and blaIMP-1 (n = 1) were identified in seven isolates. WGS
analysis could provide a vast amount of molecular epidemiological data of the
resistant isolates all at once, such as serotypes, multilocus sequence typing
(MLST) types, plasmid replicons, and resistant determinants. Since carbapenem is
the last resort to treat life-threatening E. coli infections, it is urgent to
characterize the transmission routes and develop risk management strategies to
block or slow down the transmission of resistance mechanisms and save
carbapenems.
PMID- 28686505
TI - What conclusions can be drawn from the Stockholm III rectal cancer trial in the
era of watch and wait?
PMID- 28686504
TI - Prolactin and oleic acid synergistically stimulate beta-cell proliferation and
growth in rat islets.
AB - Islet adaptation to pregnancy is largely influenced by prolactin and placental
lactogens. In addition serum lipids are significantly increased. Here, we report
the novel observation that prolactin and oleic acid synergistically stimulate
islet cell proliferation and islet growth. In neonatal rat islets, prolactin
increased proliferation 6-fold, oleic acid 3.5-fold, and their combination 15
fold. The expression of insulin in these dividing cells establishes them as beta
cells. Similar changes were seen in islet growth. This synergy is restricted to
monounsaturated fatty acids and does not occur with other islet growth factors.
Oleic acid increases prolactin-induced STAT5 phosphorylation, even though by
itself it is unable to induce STAT5 phosphorylation. Their effects on Erk1/2
phosphorylation are additive. Some of the synergy requires the formation of
oleoyl CoA and/or its metabolites. Unexpectedly, methyl oleic acid, a non
metabolizable analog of oleic acid, also shows synergy with prolactin. In
summary, prolactin and oleic acid synergistically stimulate islet cell
proliferation and islet growth in rat islets, oleic acid increases prolactin
induced STAT5 activation, and requires both the metabolism of oleic acid and non
metabolized oleic acid. Since oleic acid is the most abundant monounsaturated
fatty acid in serum that is elevated during pregnancy, it may contribute to
increased beta-cell proliferation seen during pregnancy.
PMID- 28686507
TI - Palliative Tracheostomy at the End of Life: Utilization in a Patient with
Metastatic Cancer.
PMID- 28686508
TI - An evaluation of a collaborative course for child and adolescent mental health
professionals.
AB - There is a considerable gap between the offer and the demand for mental health
treatment of children and adolescents, especially in low- and middle-income
countries (LMICs). Permanent education in these countries is a promising and
needed strategy to reduce this gap. This study was designed to evaluate the
perceived impact of an educational intervention for child and adolescent mental
health professionals in Brazil, the Child and Adolescent Mental Health
Specialization Course (CESMIA). The intervention consisted of a 360-hour
interprofessional postgraduation course. The CESMIA offered lectures and small
group case discussions for exchanging their experiences in dealing with the
patients. The students were placed in these groups according to their professions
in order to ensure a proportional distribution of healthcare professionals in
each group. The evaluation employed a quasi-experimental design by the use of a
knowledge, attitude, and practice (KAP) survey. The 39 participants reported
significant improvement in all KAP dimensions. More specifically, the data
indicated a 17% improvement for attitudes, a 9.4% increase for knowledge, and a
14% improvement for the practice dimensions. The CESMIA appeared to improve the
level of knowledge of participants and their attitudes and actions towards
patients, which reinforces the relevance of similar courses.
PMID- 28686506
TI - The impact of aging on epithelial barriers.
AB - The epithelium has many critical roles in homeostasis, including an essential
responsibility in establishing tissue barriers. In addition to the fundamental
role in separating internal from external environment, epithelial barriers
maintain nutrient, fluid, electrolyte and metabolic waste balance in multiple
organs. While, by definition, barrier function is conserved, the structure of the
epithelium varies across organs. For example, the skin barrier is a squamous
layer of cells with distinct structural features, while the lung barrier is
composed of a very thin single cell to minimize diffusion space. With the
increased focus on age-dependent alterations in organ structure and function,
there is an emerging interest in the impact of age on epithelial barriers. This
review will focus on the impact of aging on the epithelial barrier of several
organs, including the skin, lung, gastrointestinal tract and the kidney, at a
structural and functional level.
PMID- 28686509
TI - gamma-Oryzanol-Rich Black Rice Bran Extract Enhances the Innate Immune Response.
AB - The innate immune response is an important host primary defense system against
pathogens. gamma-Oryzanol is one of the nutritionally important phytoceutical
components in rice bran oil. The goal of this study was to investigate the effect
of gamma-oryzanol-rich extract from black rice bran (gammaORE) on the activation
of the innate immune system. In this study, we show that gammaORE increased the
expression of CD14 and Toll-like receptor 4 and enhanced the phagocytic activity
of RAW264.7 macrophages. Furthermore, gammaORE and its active ingredient gamma
oryzanol promoted the secretion of innate cytokines, interleukin-8, and CCL2,
which facilitate phagocytosis by RAW264.7 cells. These findings suggest that
gamma-oryzanol in the gammaORE enhances innate immune responses.
PMID- 28686510
TI - Somatostatin receptor expression in lymphomas: a source of false diagnosis of
neuroendocrine tumor at 68Ga-DOTANOC PET/CT imaging.
AB - BACKGROUND: 68Ga-DOTANOC PET/CT is routinely used to image neuroendocrine tumors
(NETs). A case of lymphoma initially thought to be NET based on a positive 68Ga
DOTANOC PET/CT was recently seen at our institution. This prompted us to
determine prospectively somatostatin receptor (SSTR) status in patients with
lymphoma by immunohistochemical analysis of SSTR subtypes 2, 3 and 5 (SSTR2,3,5)
and 68Ga-DOTANOC PET/CT imaging. MATERIAL AND METHODS: Twenty-one patients with
newly diagnosed lymphoma were referred to 68Ga-DOTANOC and FDG PET/CT prior to
any treatment. Tracer uptake was evaluated visually by two nuclear medicine
specialists. Maximum standardized uptake values (SUVmax) were determined from 14
nodal and two extranodal regions with highest uptake in each patient. Lesions
were then graded with Deauville score (1-5) on FDG PET/CT and modified Krenning
score (0-4) on 68Ga-DOTANOC PET/CT, respectively. SSTR2,3,5 status was analyzed
from routine biopsies of lymphomatous tissue and matched to corresponding PET/CT
findings. RESULTS: About 20/21 patients had FDG-positive lymphoma (Deauville
score >=3). Uptake of 68Ga-DOTANOC was regarded as positive if Krenning score was
>=2 and resulted in 13/21 (62%) patients having 68Ga-DOTANOC-positive lymphomas.
The highest uptake of 68Ga-DOTANOC was seen in Hodgkin's lymphoma of nodular
sclerosis subtype and in diffuse large B-cell lymphoma (SUVmax median 9.8 and
9.7, respectively). Both cases showed strong SSTR2 immunopositivity in tumor
cells. Some patients had SSTR2 immunopositivity predominantly in endothelial and
dendritic cells and follicular centers of lymph nodes contributing to a positive
PET/CT with probably low tumor-specific uptake. SSTR3 and SSTR5 were negative in
most lymphoma subtypes. CONCLUSIONS: According to this pilot study, 68Ga-DOTANOC
PET/CT is positive in some lymphoma subtypes which express SSTRs. These tumors
present a potential risk of being misinterpreted as NETs if a representative
tumor sample is not available. Lymphomas with high expression of SSTRs may be
amenable to treatments targeting these receptors.
PMID- 28686511
TI - A Retrospective Analysis of Central Physician Appointment System Data in a
Tertiary Health Center in Turkey.
AB - INTRODUCTION: Considerable advances have been made in hospital appointment
systems in the past 60 years. In Turkey, the Central Physician Appointment System
(CPAS) is used together with appointments made through direct presentations to
the hospital. This study evaluated CPAS data. MATERIALS AND METHODS: CPAS data
for the previous 2 years (2015, Group 1; 2016, Group 2) were evaluated
retrospectively. Department-based analysis was also performed. Total number of
clinics, CPAS capacity, number of appointments through CPAS, and numbers of
patients keeping appointments and "no shows" and ratios calculated from these
were investigated. RESULTS: Overall, 1,704,594 patients were examined in 20
departments during the 2-year period (January 1, 2015-December 31, 2016). Mean
CPAS capacity per department was 12,831 +/- 7,691 in Group 1 and 11,573 +/- 6,849
in Group 2 (p = 0.588). Ratios of appointments made through CPAS to CPAS capacity
were 0.7 in Group 1 and 0.84 in Group 2 (p = 0.009). The ratio of patients
keeping appointments made through CPAS to the number of appointments made through
CPAS was 0.772 in Group 1 and 0.775 in Group 2 (p = 0.831). The departments with
the highest number of appointments made through CPAS to CPAS capacity were
Neurosurgery in Group 1 (0.99) and Ophthalmology in Group 2 (0.99). The
department with the lowest ratio was Infectious Disease and Clinical Microbiology
in Group 1 (0.28) and Group 2 (0.45). CONCLUSIONS: The use of CPAS has increased.
However, some CPAS vacancies remain unfilled, and some appointments are not kept.
CPAS capacities must be adjusted in line with take-up rates through regular
department-based analysis.
PMID- 28686512
TI - Tracking Patients in Community-Based Palliative Care through the Centers for
Medicare & Medicaid Services Healthcare Innovation Project.
AB - BACKGROUND: Although limited, the evidence base for Community-Based Palliative
Care (CBPC) has shown that it improves patient health outcomes, increases
satisfaction, and decreases cost. Minimal data exist comparing points of entry
into palliative care and patient transition outcomes. OBJECTIVES: In 2014, Four
Seasons Compassion for Life was awarded a Centers for Medicare & Medicaid
Services Healthcare Innovation Award to expand an existing CBPC model into
additional counties and to propose a new payment approach. The goal of this
article is to evaluate the tracking of point of entry into palliative care and
patient transition outcomes in the model. DESIGN: All participant transition
outcomes are tracked from point of entry, including large and small hospitals,
nursing facilities, and home/clinic. Evaluation of tracking data was conducted
over the first two years of the project (September 1, 2014-September 1, 2016).
RESULTS: A total of 2482 patients entered the project, 905 through smaller
hospitals (<300 beds, 32%), 474 through larger hospital systems (>500 beds, 17%),
823 from nursing facilities (29%), and 640 in the home/clinic (22%). Hospice
transition was highest with home/clinic referrals, followed by nursing
facilities, smaller hospitals, and larger hospitals. Palliative care deaths and
discharges are higher in larger hospitals. Re-enrollment back into palliative
care after previous discharge occurred in 177 (17.8%) of discharged patients.
CONCLUSION: CBPC leads to the highest percentage of hospice transitions coming
from the home/clinic setting. Differences between small and large hospitals
demonstrate a different patient population with higher transitions to hospice and
lower palliative care deaths in smaller hospitals.
PMID- 28686513
TI - Metagenomic Sequencing Detects Respiratory Pathogens in Hematopoietic Cellular
Transplant Patients.
PMID- 28686515
TI - Tracing Dietary Mercury Histochemically, with Autometallography, through the
Liver to the Ovaries and Spawned Eggs of the Spot, a Temperate Coastal Marine
Fish.
AB - Exposure to mercury (Hg) results in reproductive abnormalities and deficiencies
in female fish. We traced the maternal assimilation and redistribution of dietary
inorganic (HgII) and organic (MeHg) forms of Hg in a coastal marine fish, the
Spot Leiostomus xanthurus. We conducted a 90-d laboratory experiment in which
treatment Spot were fed muscle of Blue Marlin Makaira nigricans with elevated
concentrations of Hg mixed with a commercial fish food, while control Spot were
fed only commercial food pellets. Gonadal maturation was induced by shortening
the photoperiod and increasing the temperature. Spawning was induced by
intramuscular injection of human chorionic gonadotropin at 100 IU/kg. Solid
sampling atomic absorption spectrophotometry measured the total Hg (THg), HgII,
and MeHg in Blue Marlin muscle. Autometallography located Hg-sulfide granules in
the liver, ovaries, and spawned eggs, and densitometry provided comparisons of Hg
sulfide granules in the ovaries of treatment and control Spot. Overall, the
intensity and prevalence of Hg-sulfide granules were greater in the liver,
ovaries, and eggs from treatment Spot than in those from controls. The tissue and
cellular distribution of Hg-sulfide granules differed. Received November 18,
2016; accepted June 18, 2017.
PMID- 28686514
TI - Substrate rigidity-dependent positive feedback regulation between YAP and ROCK2.
AB - Extracellular matrix (ECM) stiffness influences gene expression, leading to
modulation of various cellular functions. While ROCK2 regulates actomyosin
activity as well as cell migration and proliferation, expression of ROCK2 is
increased in response to stiffening ECM. However, the mechanism underlying
rigidity-dependent ROCK2 expression remains elusive. Here, we show that YAP, a
mechanically regulated transcription coactivator, upregulates ROCK2 expression in
an ECM rigidity-dependent manner. YAP interacted with the ROCK2 promoter region
in an actomyosin activity-dependent manner. Knockdown of YAP decreased ROCK2
expression while activity of the ROCK2 promoter was upregulated by expressing
constitutively active YAP. Furthermore, we found that ROCK2 expression promotes
transcriptional activation by YAP. Our results reveal a novel positive feedback
loop between YAP and ROCK2, which is modulated by ECM stiffness.
PMID- 28686516
TI - Standardized Cirsium setidens Nakai Ethanolic Extract Suppresses Adipogenesis and
Regulates Lipid Metabolisms in 3T3-L1 Adipocytes and C57BL/6J Mice Fed High-Fat
Diets.
AB - Cirsium setidens Nakai, a wild perennial herb, grows mainly in Gangwon province,
Korea, and has been reported to contain bioactive ingredients with various
medicinal activities, including the treatment of edema, bleeding, and hemoptysis.
However, the potential antiobesity effects of C. setidens Nakai have not been
fully investigated. This study evaluated the antiobesity effect of standardized
C. setidens Nakai ethanolic extract (CNE) in 3T3-L1 adipocytes and in obese
C57BL/6J mice fed a high-fat diet. CNE suppressed the expression of lipogenic
genes and increased the expression of lipolytic genes. The antiadipogenic and
antilipogenic effects of CNE appear to be mediated by the inhibition of
peroxisome proliferator-activated receptor gamma (PPARgamma) and CCAAT/enhancer
binding protein (C/EBP) expressions. Moreover, CNE stimulated fatty acid
oxidation in an AMPK-dependent manner. CNE-treated groups of C57BL/6J mice showed
reduced body weights and adipose tissue weight and improved serum lipid profiles
through the downregulation of PPARgamma, C/EBPalpha, fatty acid binding protein 4
(FABP4), sterol regulatory element binding protein-1c (SREBP-1c), and fatty acid
synthase (FAS) and the upregulation of adiponectin and carnitine
palmitoyltransferase-1 (CPT-1) in obese C57BL/6J mice fed a high-fat diet. These
results suggest that CNE may have an antiobesity effect on adipogenesis and lipid
metabolism in vitro and in vivo and present the possibility of developing a
treatment for obesity with nontoxic natural resources.
PMID- 28686517
TI - Osteoporosis Management.
AB - The clinical update serves as a brief review of recently published, high-impact,
and potentially practice changing journal articles summarized for our readers.
Topics include menopause, sexual dysfunction, breast health, contraception,
osteoporosis, and cardiovascular disease. In this clinical update, we selected
recent publications relevant to osteoporosis management. We highlight articles on
the safety of long-term use of denosumab and bisphosphonates, fracture risk after
discontinuing menopausal hormone therapy, calcium intake and cardiovascular risk,
as well as the value of repeat dual X-ray absorptiometry scanning to monitor
those on osteoporosis treatment.
PMID- 28686519
TI - Regulatory Fit Improves Fitness for People With Low Exercise Experience.
AB - Considering only 20.8% of American adults meet current physical activity
recommendations, it is important to examine the psychological processes that
affect exercise motivation and behavior. Drawing from regulatory fit theory, this
study examined how manipulating regulatory focus and reward structures would
affect exercise performance, with a specific interest in investigating whether
exercise experience would moderate regulatory fit effects. We predicted that
regulatory fit effects would appear only for participants with low exercise
experience. One hundred and sixty-five young adults completed strength training
exercise tasks (i.e., sit-ups, squats, plank, and wall-sit) in regulatory match
or mismatch conditions. Consistent with predictions, only participants low in
experience in regulatory match conditions exercised more compared with those in
regulatory mismatch conditions. Although this is the first study manipulating
regulatory fit in a controlled setting to examine exercise behavior, findings
suggest that generating regulatory fit could positively influence those low in
exercise experience.
PMID- 28686518
TI - Connexins and microRNAs: Interlinked players in regulating islet function?
AB - Pancreatic beta-cells are connected to neighboring endocrine cells through the
adherin proteins and gap junctions. Connexin 36 (Cx36) is one of the most well
studied and abundantly expressed gap-junction proteins within rodent islets,
which is important in coordinated insulin secretion. The expression of connexins
is regulated at various levels and by several mechanisms; one of which is via
microRNAs. In past 2 decades, microRNAs (miRNAs) have emerged as key molecules in
developmental, physiologic and pathological processes. However, very few studies
have demonstrated miRNA-mediated regulation of connexins. Even though there are
no reports yet on miRNAs and Cx36; we envisage that considering the important
role of connexins and microRNAs in insulin secretion, there would be common
pathways interlinking these biomolecules. Here, we discuss the current literature
on connexins and miRNAs specifically with reference to islet function.
PMID- 28686520
TI - Mindfulness-based interventions for women with breast cancer: an updated
systematic review and meta-analysis.
AB - BACKGROUND: The aim of this meta-analysis was to systematically update the
evidence for mindfulness-based stress reduction (MBSR) and mindfulness-based
cognitive therapy (MBCT) in women with breast cancer. MATERIAL AND METHODS: In
October 2016, PubMed, Scopus, and Central were searched for randomized controlled
trials on MBSR/MBCT in breast cancer patients. The primary outcome was health
related quality of life. Secondary outcomes were fatigue, sleep stress,
depression, anxiety, and safety. For each outcome, standardized mean differences
(SMD/Hedges' g) and 95% confidence intervals (CI) were calculated. Risk of bias
was assessed by the Cochrane risk of bias tool. RESULTS: The Literature search
identified 14 articles on 10 studies that included 1709 participants. The overall
risk of bias was unclear, except for risk of low attrition bias and low other
bias. Compared to usual care, significant post-intervention effects of MBSR/MBCT
were found for health-related quality of life (SMD = .21; 95%CI = [.04-.39]),
fatigue (SMD = -.28; 95%CI = [-.43 to -.14]), sleep (SMD = -.23; 95%CI = [-.40 to
-.05]), stress (SMD = -.33; 95%CI = [-.61 to -.05]), anxiety (SMD = -.28; 95%CI =
[-.39 to -.16]), and depression (SMD = -.34; 95%CI = [-.46 to -.21]). Up to 6
months after baseline effects were significant for: anxiety (SMD = -.28; 95%CI =
[-.47 to -.09]) and depression (SMD = -.26; 95%CI = [-.47 to -.04]); and
significant for anxiety (SMD = -.21; 95%CI = [-.40 to -.03]) up to 12 months
after baseline. Compared to other active interventions, significant effects were
only found post-intervention and only for anxiety (SMD = -.45; 95%CI = [-.71 to
.18]) and depression (SMD = -.39; 95%CI = [-.65 to -.14]). However, average
effects were all below the threshold of minimal clinically important differences.
Effects were robust against potential methodological bias. Adverse events were
insufficiently reported. CONCLUSIONS: This meta-analysis revealed evidence for
the short-term effectiveness and safety of mindfulness-based interventions in
women with breast cancer. However, their clinical relevance remains unclear.
Further research is needed.
PMID- 28686521
TI - Experiences of pregnancy complications: Voices from central Haiti.
AB - The purpose of this study was to explore the lived experience of pregnancy/birth
complications in central Haiti from the perspectives of skilled birth attendants
(saj fanm), traditional birth attendants (matwons), and postpartum mothers.
Hermeneutic phenomenology guided the study. With the assistance of a Creole
English translator, four saj fanm, ten matwons, and seven postpartum mothers were
interviewed. Their stories explain barriers and challenges to safe motherhood
serious limitations in transportation, staffing, and lack of the most basic of
material resources, but also illustrate tremendous resiliency, spirituality,
power of partnerships, and commonsense solutions to problems impacting
maternal/newborn health in central Haiti. Haiti has one the world's highest
maternal and neonatal mortality, and findings of this study provide perspective
of this reality from those most affected by it-Haitian mothers and front-line
maternity workers.
PMID- 28686522
TI - Asbestos-related disease in upholsterers.
AB - Before its use was banned in developed countries, asbestos was widely applied in
upholstery. However, the risk of asbestos diseases among upholsterers has only
rarely been reported. In this case series, we present a first series of 6 workers
employed in small workshops who developed several asbestos-related diseases,
including pleural plaques, pleural fibrosis, and asbestosis. Exposures were
intermittent and difficult to quantify, but lung asbestos content assessed by
bronchoalveolar lavage was high in the 3 patients evaluated. In conclusion,
upholstery work should be considered an at-risk occupation for developing
asbestos-related diseases during the 20th century.
PMID- 28686523
TI - Clinical utility of therapeutic drug monitoring in biological disease modifying
anti-rheumatic drug treatment of rheumatic disorders: a systematic narrative
review.
AB - INTRODUCTION: Biological Disease Modifying Anti-Rheumatic Drugs (bDMARDs) have
improved the treatment outcomes of inflammatory rheumatic diseases including
Rheumatoid Arthritis and spondyloarthropathies. Inter-individual variation exists
in (maintenance of) response to bDMARDs. Therapeutic Drug Monitoring (TDM) of
bDMARDs could potentially help in optimizing treatment for the individual
patient. Areas covered: Evidence of clinical utility of TDM in bDMARD treatment
is reviewed. Different clinical scenarios will be discussed, including:
prediction of response after start of treatment, prediction of response to a next
bDMARD in case of treatment failure of the first, prediction of successful dose
reduction or discontinuation in case of low disease activity, prediction of
response to dose-escalation in case of active disease and prediction of response
to bDMARD in case of flare in disease activity. Expert opinion: The limited
available evidence does often not report important outcomes for diagnostic
studies, such as sensitivity and specificity. In most clinical relevant
scenarios, predictive value of serum (anti-) drug levels is absent, therefore the
use of TDM of bDMARDs cannot be advocated. Well-designed prospective studies
should be done to further investigate the promising scenarios to determine the
place of TDM in clinical practice.
PMID- 28686524
TI - Hunting for abscopal and bystander effects: clinical exploitation of non-targeted
effects induced by partial high-single-dose irradiation of the hypoxic tumour
segment in oligometastatic patients.
PMID- 28686525
TI - Kidney biopsy in AA amyloidosis: impact of histopathology on prognosis.
AB - In AA amyloidosis, while kidney biopsy is widely considered for diagnosis by
clinicians, there is no evidence that the detailed investigation of renal
histopathology can be utilized for the prognosis and clinical outcomes. In this
study, we aimed to obtain whether histopathologic findings in kidney biopsy of AA
amyloidosis might have prognostic and clinical value. This is a retrospective
cohort study that included 38 patients who were diagnosed with AA amyloidosis by
kidney biopsy between 2005 and 2013.The kidney biopsy specimens of patients were
evaluated and graded for several characteristics of histopathological lesions and
their relationship with renal outcomes. Segmental amyloid deposition in the
kidney biopsy was seen in 29%, global amyloid deposition in 71, diffuse
involvement of glomeruli in 84.2%, focal involvement in 7%, glomerular
enlargement in 53%, tubular atrophy in 75% and interstitial fibrosis in 78% of
patients. Histopathologically, glomerular enlargement, interstitial fibrosis,
tubular atrophy, interstitial inflammation and global amyloid deposition were
significantly associated with lower estimated glomerular filtration rate (eGFR)
(p = .02, p < .001, p = .001, p = .009, p = .002, respectively) in univariate
analysis. In multivariate analysis, tubular atrophy was the only predictor of
eGFR (p = .019 B = -20.573). In the follow-up at an average of 27 months, 18
patients developed end-stage renal disease (ESRD). Among them, global amyloid
deposition was the only risk factor for the development of ESRD (p = .01, OR =
18.750, %95 CI= 2.021-173.942). This is the first study showing that the
histopathological findings in kidney biopsy of AA amyloidosis might have a
prognostic and clinical value for renal outcomes.
PMID- 28686527
TI - Factors Associated with Achievement of Clinically Significant Weight Loss by
Women in a National Nonprofit Weight Loss Program.
AB - BACKGROUND: Clinically significant weight loss (CSWL) is >=5% of initial weight.
The purpose of the study is to determine factors associated with women achieving
CSWL in Take Off Pounds Sensibly (TOPS), a national, nonprofit weight loss
program. METHODS: This is a retrospective analysis of 48,674 females who joined
TOPS from 2005 to 2011 and had a birth date in the database. Predictors of CSWL
were evaluated using log-binomial regression and adjusted relative risks [99% CI]
for participant age, initial weight, number of members per chapter, and chapter
age. RESULTS: Older women were more likely to achieve CSWL, with women >=70 years
1.23 (1.18, 1.28) times more likely to achieve CSWL compared to women 18 to <45
years. Women who weighed 113 to <136 kg and >=136 kg were 1.06 (1.02, 1.10) and
1.07 (1.02, 1.14) times more likely to achieve CSWL compared to women <80 kg,
respectively. Women in chapters with 25 to <35 members and >=35 members more were
1.09 (1.05, 1.13) and 1.14 (1.10, 1.18) times more likely to achieve CSWL than
those in chapters with less than 15 members. Women in older chapters were less
likely to achieve CSWL, with women in chapters 10 to 20 years old 0.95 (0.92,
0.99) times as likely to lose weight as those in chapters less than 10 years old.
CONCLUSIONS: Women in TOPS were more likely to achieve CSWL if older, >=113 kg,
and in larger, newer chapters. Future studies should address ways to modify the
program to improve achievement of CSWL.
PMID- 28686528
TI - The Vaginal Pressure Inducer: A New Device to Test the (Un)pleasurableness and
Tolerance of Vaginal Pressure and the Influence of Sexual Stimuli.
AB - To better understand the impact of sexual stimuli on genital pain, a new
instrument was developed: the Vaginal Pressure Inducer (VPI). We administered
gradually increasing vaginal pressure with the VPI to sexually functional women
as they watched a neutral, erotic, or explicit sex film. Women had higher
unpleasantness thresholds in a sexual context compared to a nonsexual context.
Moreover, ratings of pleasurableness were higher in the sexual compared to
neutral context and most so during the explicit sexual film. These results
provide initial support for the suitability of the VPI to study determinants of
pleasant and unpleasant appraisal of vaginal pressure.
PMID- 28686526
TI - In life there is death: How epithelial tissue barriers are preserved despite the
challenge of apoptosis.
AB - Apoptosis is a ubiquitous mode of programmed cell death that is found in healthy
organs and can be stimulated by many toxic stresses. When it occurs in epithelia,
apoptosis presents major challenges to tissue integrity. Apoptotic corpses can
promote inflammatory and autoimmune responses if they are retained, and the
cellular fragmentation that accompanies apoptosis can potentially compromise the
epithelial barrier. Here we discuss 2 homeostatic mechanisms that allow epithelia
to circumvent these potential risks: clearance of apoptotic corpses by
professional and non-professional phagocytes and physical expulsion of apoptotic
cells by apical extrusion. Extrusion and phagocytosis may represent complementary
responses that preserve epithelial integrity despite the inevitable challenge of
apoptosis.
PMID- 28686529
TI - Identifying Cognitive Impairment in Hospitalized Older Adults to Prevent
Readmission: Two Case Studies.
AB - OBJECTIVE: To describe two patient outcomes post-discharge from an acute hospital
admission. Both patients underwent cognitive testing during hospitalization.
METHODS: A battery of cognitive tests was administered to two hospitalized older
adult patients. Both patients were evaluated in their homes within 72 hours of
discharge and again at 14- and 30-days by a nurse practitioner. RESULTS: One of
the patients was readmitted within 30 days of hospital discharge due to
complications from an amputation. This patient did not perform well on cognitive
measures which may have been related to his pain levels and/or his medication
regimen. CONCLUSIONS: Not all readmissions are avoidable; however, if
readmissions are related to cognitive impairment, implementing strategies
tailored to this population may reduce readmission rates. CLINICAL IMPLICATIONS:
Risk factors for readmission should be identified so the discharge team can
develop a tailored plan of care. Including both the patient and an informal
caregiver may reduce the chance of a hospital readmission in older adults with
cognitive impairment regardless of the etiology.
PMID- 28686531
TI - Microenvironment and Dose-Delivery-Dependent Response after Exposure to Ionizing
Radiation in Human Colorectal Cancer Cell Lines.
AB - A significant body of knowledge about radiobiology is based on studies of single
dose cellular irradiation, despite the fact that conventional clinical
applications using dose fractionation. In addition, cellular radiation response
strongly depends on cell-cell and cell-extracellular matrix (ECM) interactions,
which are poorly established in cancer cells grown under standard 2D cell culture
conditions. In this study, we investigated the response of human colorectal
carcinoma (CRC) DLD1 and HT29 cell lines, bearing distinct p53 mutations, to a
single 2 or 10 Gy dose or fractionated 5 * 2 Gy doses of radiation using global
transcriptomics analysis. To examine cellular response to radiation in a cell-ECM
interaction-dependent manner, CRC cells were grown under laminin-rich ECM 3D cell
culture conditions. Microarray data analysis revealed that, overall, a total of
1,573 and 935 genes were differentially expressed (fold change >1.5; P < 0.05) in
DLD1 and HT29 cells, respectively, at 4 h postirradiation. However, compared to a
single dose of radiation, fractionated doses resulted in significantly different
transcriptomic response in both CRC cell lines. Furthermore, pathway enrichment
analysis indicated that p53 pathway and cell cycle/DNA damage repair or immune
response functional categories were most significantly altered in DLD1 or HT29
cells, respectively, after fractionated irradiations. Novel observations of
radiation-response-mediated activation of pro-survival pathways in CRC cells
grown under lr-ECM 3D cell culture conditions using fractionated doses provide
new directions for the development of more efficient radiotherapy strategies. Our
results also indicated that cell line specific radiation response with or without
activation of the conventional p53 pathway is ECM dependent, suggesting that the
ECM is a key component in cellular radiation response.
PMID- 28686532
TI - Management of hydrocephalus associated with autoimmune diseases: a series of 19
cases.
AB - OBJECTIVES: To analyze the diagnosis and treatment of hydrocephalus associated
with autoimmune diseases and to explore the possible mechanism of hydrocephalus
in these patients. METHODS: A retrospective case series study was conducted at
Peking Union Medical College Hospital, Beijing, China. Files were retrieved from
the hospital archives by screening records from Jan 1990 to Jan 2016. Medical
records were screened for data regarding (1) the number of patients diagnosed
with hydrocephalus associated with autoimmune diseases, (2) the clinical
manifestation of hydrocephalus associated with autoimmune disease, and (3) the
outcomes of these patients treated with medication or ventriculoperitoneal shunt
(VPS). RESULTS: A total of 19 of 19,643 hospitalized autoimmune diseases patients
were found to have hydrocephalus. Seven of the 19 patients had systemic lupus
erythematosus (SLE), 3 patients had Sjogren's syndrome, 2 patients had rheumatoid
arthritis (RA), 1 patient had connective tissue disease, 1 patient had juvenile
idiopathic arthritis (JIA), 1 patient had Guillain-Barre syndrome (GBS), 1
patient had systemic sclerosis, 1 patient had Crohn's disease, 1 patient had
relapsing polychondritis (RPC), and 1 patient had autoinflammatory disease (AID).
Of the 19 patients, 13 received medication treatment, and the most commonly used
drugs were corticosteroids and mannitol. A total of 6 patients received both
medication therapy and VPS treatment with a programable valve. After average
follow-up lengths of 11 months for patients who received VPS and 8.2 for patients
who received medical treatment, the clinical symptoms of patients treated by VPS
or medication were improved (83% (5/6) vs. 15.4% (2/13), respectively), patients
were in stable condition (17% (1/6) vs. 30.8% (4/13), respectively), and
mortality decreased (0% vs. 53.8% (7/13), respectively). CONCLUSIONS: VPS along
with corticosteroids and immunosuppressants represents an effective treatment
approach for patients who suffer from hydrocephalus associated with autoimmune
diseases.
PMID- 28686533
TI - Associative Learning of Social Value in Dynamic Groups.
AB - Although humans live in societies that regularly demand engaging with multiple
people simultaneously, little is known about social learning in group settings.
In two experiments, we combined a Pavlovian learning framework with dyadic
economic games to test whether blocking mechanisms support value-based social
learning in the gain (altruistic dictators) and loss (greedy robbers) domains.
Subjects first learned about an altruistic dictator, who subsequently made
altruistic splits collectively with a partner. Results revealed that because the
presence of the dictator already predicted the outcome, subjects did not learn to
associate value with the partner. This social blocking effect was not observed in
the loss domain: A kind robber's partner, who could steal all the subjects' money
but stole little, acquired highly positive value-which biased subjects'
subsequent behavior. These findings reveal how Pavlovian mechanisms support
efficient social learning, while also demonstrating that violations of social
expectations can attenuate how readily these mechanisms are recruited.
PMID- 28686534
TI - New Model for Estimating Glomerular Filtration Rate in Patients With Cancer.
AB - Purpose The glomerular filtration rate (GFR) is essential for carboplatin
chemotherapy dosing; however, the best method to estimate GFR in patients with
cancer is unknown. We identify the most accurate and least biased method. Methods
We obtained data on age, sex, height, weight, serum creatinine concentrations,
and results for GFR from chromium-51 (51Cr) EDTA excretion measurements (51Cr
EDTA GFR) from white patients >= 18 years of age with histologically confirmed
cancer diagnoses at the Cambridge University Hospital NHS Trust, United Kingdom.
We developed a new multivariable linear model for GFR using statistical
regression analysis. 51Cr-EDTA GFR was compared with the estimated GFR (eGFR)
from seven published models and our new model, using the statistics root-mean
squared-error (RMSE) and median residual and on an internal and external
validation data set. We performed a comparison of carboplatin dosing accuracy on
the basis of an absolute percentage error > 20%. Results Between August 2006 and
January 2013, data from 2,471 patients were obtained. The new model improved the
eGFR accuracy (RMSE, 15.00 mL/min; 95% CI, 14.12 to 16.00 mL/min) compared with
all published models. Body surface area (BSA)-adjusted chronic kidney disease
epidemiology (CKD-EPI) was the most accurate published model for eGFR (RMSE,
16.30 mL/min; 95% CI, 15.34 to 17.38 mL/min) for the internal validation set.
Importantly, the new model reduced the fraction of patients with a carboplatin
dose absolute percentage error > 20% to 14.17% in contrast to 18.62% for the BSA
adjusted CKD-EPI and 25.51% for the Cockcroft-Gault formula. The results were
externally validated. Conclusion In a large data set from patients with cancer,
BSA-adjusted CKD-EPI is the most accurate published model to predict GFR. The new
model improves this estimation and may present a new standard of care.
PMID- 28686536
TI - Dietary Protein Intake above the Current RDA and Bone Health: A Systematic Review
and Meta-Analysis.
AB - Dietary intake of protein is fundamental for optimal acquisition and maintenance
of bone across all life stages; however, it has been hypothesized that intakes
above the current recommended dietary allowance (RDA) might be beneficial for
bone health. We utilized the Preferred Reporting Items for Systematic Reviews and
Meta-Analyses (PRISMA) guidelines when preparing and reporting this systematic
review and meta-analysis. A literature search strategy through April 11, 2017,
was developed for the following 3 databases: PubMed, Ovid Medline, and Agricola.
Included studies were those randomized controlled trials and prospective cohort
studies among healthy adults ages 18 and older that examined the relationships
between varying doses of protein intake at or above the current U.S. RDA (0.8
g/kg/d or 10%-15% of total caloric intake) from any source on fracture, bone
mineral density (BMD)/bone mineral content (BMC), and/or markers of bone
turnover. Twenty-nine articles were included for data extraction (16 randomized
controlled trials [RCTs] and 13 prospective cohort studies). Meta-analysis of the
prospective cohort studies showed high vs low protein intakes resulted in a
statistically significant 16% decrease in hip fractures (standardized mean
difference [SMD] = 0.84, 95% confidence interval [CI], 0.73, 0.95; I2 = 36.8%).
Data from studies included in these analyses collectively lean toward the
hypothesis that protein intake above the current RDA is beneficial to BMD at
several sites. This systematic review supports that protein intakes above the
current RDA may have some beneficial role in preventing hip fractures and BMD
loss. There were no differences between animal or plant proteins, although data
in this area were scarce. Larger, long-term, and more well-controlled clinical
trials measuring fracture outcomes and BMD are needed to adequately assess
whether protein intake above the current RDA is beneficial as a preventative
measure and/or intervention strategy for osteoporosis. Key teaching points: * *
Bone health is a multifactorial musculoskeletal issue, and optimal protein
intakes are key in developing and maintaining bone throughout the life span. * *
Dietary protein at levels above the current RDA may be beneficial in preventing
hip fractures and BMD loss. * * Plant vs animal proteins do not seem to differ in
their ability to prevent bone loss; however, data in this area are scarce. * *
Larger, long-term RCTs using women not using hormone replacement therapy (HRT)
are needed to adequately assess the magnitude of impact that protein intakes
above the RDA have on preventing bone loss.
PMID- 28686535
TI - Prospective Evaluation of Magnetic Resonance Imaging and [18F]Fluorodeoxyglucose
Positron Emission Tomography-Computed Tomography at Diagnosis and Before
Maintenance Therapy in Symptomatic Patients With Multiple Myeloma Included in the
IFM/DFCI 2009 Trial: Results of the IMAJEM Study.
AB - Purpose Magnetic resonance imaging (MRI) and positron emission tomography
computed tomography (PET-CT) are important imaging techniques in multiple myeloma
(MM). We conducted a prospective trial in patients with MM aimed at comparing MRI
and PET-CT with respect to the detection of bone lesions at diagnosis and the
prognostic value of the techniques. Patients and Methods One hundred thirty-four
patients received a combination of lenalidomide, bortezomib, and dexamethasone
(RVD) with or without autologous stem-cell transplantation, followed by
lenalidomide maintenance. PET-CT and MRI were performed at diagnosis, after three
cycles of RVD, and before maintenance therapy. The primary end point was the
detection of bone lesions at diagnosis by MRI versus PET-CT. Secondary end points
included the prognostic impact of MRI and PET-CT regarding progression-free (PFS)
and overall survival (OS). Results At diagnosis, MRI results were positive in 127
of 134 patients (95%), and PET-CT results were positive in 122 of 134 patients
(91%; P = .33). Normalization of MRI after three cycles of RVD and before
maintenance was not predictive of PFS or OS. PET-CT became normal after three
cycles of RVD in 32% of the patients with a positive evaluation at baseline, and
PFS was improved in this group (30-month PFS, 78.7% v 56.8%, respectively). PET
CT normalization before maintenance was described in 62% of the patients who were
positive at baseline. This was associated with better PFS and OS. Extramedullary
disease at diagnosis was an independent prognostic factor for PFS and OS, whereas
PET-CT normalization before maintenance was an independent prognostic factor for
PFS. Conclusion There is no difference in the detection of bone lesions at
diagnosis when comparing PET-CT and MRI. PET-CT is a powerful tool to evaluate
the prognosis of de novo myeloma.
PMID- 28686537
TI - Far from Standardized: Using Surgical Videos to Identify Variation in Technique
for Laparoscopic Sleeve Gastrectomy.
AB - BACKGROUND: Video assessment is an emerging tool for understanding variation in
surgical technique. METHODS: Representative videos of laparoscopic sleeve
gastrectomy (LSG) were voluntarily submitted by 20 surgeons who participated in a
statewide quality improvement collaborative. The amount of time required to
complete the salient steps of the operation was measured and variations in the
tasks performed during each step were captured. RESULTS: Twenty-two videos of LSG
were submitted and 11 videos included concurrent hiatal hernia repair. Data
obtained from video analysis identified variation in time to complete each step
of the procedure: prestapling dissection of stomach (5-25 minutes), gastric
stapling (8-20 minutes), and management of the staple line (1-25 minutes). Time
required to perform a hiatal hernia repair also varied (1-26 minutes), as did the
type of repair: 55% were performed with a posterior cruropexy, 27% were performed
with an anterior cruropexy, and 18% were performed with both. Ten different
permutations of staple heights and buttressing material were used during division
of the stomach with a gastric stapler. Management of the staple line included use
of buttressing (64%), fibrin sealant (36%), oversewing (9%), surgical clips
(18%), imbrication of the staple line (36%), and omentoplasty (55%). CONCLUSIONS:
LSG technique is not uniform. Video analysis identified variation in (1) time to
complete each step of the procedure, (2) hiatal hernia repair technique, (3)
stapling technique, and (4) post-transection staple line management. Future
efforts linking video analysis with clinical outcomes can provide objective
evidence to support best practices.
PMID- 28686538
TI - Differential Intraocular Pressure Measurements by Tonometry and Direct
Cannulation After Treatment with Soluble Adenylyl Cyclase Inhibitors.
AB - PURPOSE: To validate the increase in intraocular pressure (IOP) caused by soluble
adenylyl cyclase (sAC) inhibitors and determine reasons behind variation in IOP
measurements performed by tonometry. METHODS: C57BL/6J mice were administered
DMSO solubilized sAC inhibitors (KH7 or LRE-1) by intraperitoneal injection. Two
hours post-treatment, mice were anesthetized with avertin or
ketamine/xylazine/acepromazine (KXA). IOP was measured by a rebound tonometer or
direct cannulation of the anterior chamber. Spectral-domain optical coherence
tomography was used to measure anterior chamber depth and corneal thickness in
live mice. Outflow facility was measured in perfused, enucleated mouse eyes.
RESULTS: Compared with DMSO controls, KH7 treatment caused an increased IOP in
avertin- and KXA-anesthetized mice when measured by direct cannulation [avertin:
14.4 +/- 2.1 mmHg vs. 11.1 +/- 1.0 mmHg (P = 0.003); KXA: 14.4 +/- 1.0 mmHg vs.
11.3 +/- 0.8 mmHg (P < 0.001)] and tonometry [avertin: 10.8 +/- 1.4 mmHg vs. 7.4
+/- 0.6 mmHg (P < 0.001); KXA: 11.9 +/- 0.9 mmHg vs. 10.3 +/- 1.7 mmHg (P =
0.283)]. However, treatment with KH7 in nonanesthetized mice showed a significant
decrease in IOP measured by tonometry and compared with DMSO-treated animals
[13.1 +/- 2.6 mmHg vs. 15.6 +/- 0.5 mmHg (P = 0.003)]. Both KH7- and DMSO-treated
groups anesthetized with avertin showed increased corneal thickness, whereas KH7
treated mice anesthetized with KXA exhibited a shallower anterior chamber
compared with untreated mice. KH7 decreased outflow facility by 85.1% in
nonanesthetized, enucleated eyes (P < 0.003). CONCLUSIONS: Systemically
administered DMSO and anesthesia have significant effects on anterior chamber
characteristics, resulting in altered IOP readings measured by tonometry. In the
presence of DMSO and anesthesia, tonometry IOP readings should be confirmed with
direct cannulation.
PMID- 28686540
TI - Replicon Particle Expressing the E2 Glycoprotein of Bovine Viral Diarrhea Virus
Immunization and Evaluation of Antibody Response.
AB - The objective of this study was to develop a new antigen delivery system using an
alphavirus replicon particle (RP) to induce humoral antibody responses against
bovine viral diarrhea virus (BVDV) recombinant antigen produced from envelope
glycoprotein E2. An alphavirus RP expressing the E2 glycoprotein of BVDV was used
for immunization of pigs. A fluorescent microsphere immunoassay (FMIA) has been
applied to detect BVDV E2 antigen-specific antibody isotype in pig immunized with
alphavirus RP. Full-length BVDV E2 (aa 1-375) was cleaved into several pieces,
eight E2 DNA fragments, including full-length DNA, were cloned into expression
vector pHUE, and the recombinant proteins expressed in BL-21 (DE3) Escherichia
coli. After successful conjugation of purified proteins with microsphere beads, a
multiplex FMIA platform was constructed, and BVDV E2 alphavirus-based RP
immunized animal serum samples were tested in the presence of bead-bound antigen
targets. The results were represented as mean fluorescence intensity (MFI); the
MFI values were converted to sample value/positive value (S/P) ratios. BVDV E2
(aa 1-183) showed the highest MFI values of eight recombinant E2 fragments when
the specific activity of each fragment was tested. In immunized animals, data for
BVDV E2-specific IgA, IgG, and IgM in serum and only IgG and IgA in oral fluids
were recorded. The MFI values for the positive serum sample showed a 100-fold
increase compared with the negative serum sample. Antibody isotype to BVDV E2
antigens showed that IgG > IgM > IgA in serum, whereas IgG > IgA > IgM in oral
fluids. The data presented in this study suggested that boosting with the same
doses of alphavirus RP in 3-week intervals may potentially enhance antibody
response. The experimental results demonstrate that alphavirus RP-expressing BVDV
E2 antigen induces antibody response in pig.
PMID- 28686541
TI - The role of probiotics in children with autism spectrum disorder: A prospective,
open-label study.
AB - OBJECTIVE: There are limited data on the efficacy of probiotics in children with
ASD, therefore, this study aims to evaluate the efficacy and tolerability of
probiotics in an Egyptian cohort of children with ASD. METHODS: Gastrointestinal
(GI) flora were assessed by quantitative real-time PCR of stool samples of 30
autistic children from 5 to 9 years old. GI symptoms of autistic children were
assessed with a modified six-item Gastrointestinal Severity Index (6-GSI)
questionnaire, and autistic symptoms were assessed with Autism Treatment
Evaluation Checklist (ATEC) before and after 3 months of supplementation of
probiotics nutritional supplement formula (each gram contains 100 * 106 colony
forming units of three probiotic strains; Lactobacillus acidophilus,
Lactobacillus rhamnosus and Bifidobacteria longum). RESULTS: After probiotic
supplementation, the stool PCR of autistic children showed increases in the
colony counts of Bifidobacteria and Lactobacilli levels, with a significant
reduction in their body weight as well as significant improvements in the
severity of autism (assessed by the ATEC), and gastrointestinal symptoms
(assessed by the 6-GSI) compared to the baseline evaluated at the start of the
study. CONCLUSIONS: We concluded that probiotics have beneficial effects on both
behavioral and GI manifestations of ASD. Probiotics (a non-pharmacological and
relatively risk-free option) could be recommended for children with ASD as an
adjuvant therapy. At this stage, this study is a single center with a small
number of patients and a great deal of additional wide-scale randomized
controlled trials are needed to critically confirm the efficacy of probiotics in
ASD. TRIAL REGISTRATION NUMBER: UMIN-CTR Study Design: Trial Number
UMIN000026157.
PMID- 28686542
TI - Polyunsaturated fatty acids and endocannabinoids in health and disease.
AB - Polyunsaturated fatty acids (PUFAs) are lipid derivatives of omega-3
(docosahexaenoic acid, DHA, and eicosapentaenoic acid, EPA) or of omega-6
(arachidonic acid, ARA) synthesized from membrane phospholipids and used as a
precursor for endocannabinoids (ECs). They mediate significant effects in the
fine-tune adjustment of body homeostasis. Phyto- and synthetic cannabinoids also
rule the daily life of billions worldwide, as they are involved in obesity,
depression and drug addiction. Consequently, there is growing interest to reveal
novel active compounds in this field. Cloning of cannabinoid receptors in the 90s
and the identification of the endogenous mediators arachidonylethanolamide
(anandamide, AEA) and 2-arachidonyglycerol (2-AG), led to the characterization of
the endocannabinoid system (ECS), together with their metabolizing enzymes and
membrane transporters. Today, the ECS is known to be involved in diverse
functions such as appetite control, food intake, energy balance, neuroprotection,
neurodegenerative diseases, stroke, mood disorders, emesis, modulation of pain,
inflammatory responses, as well as in cancer therapy. Western diet as well as
restriction of micronutrients and fatty acids, such as DHA, could be related to
altered production of pro-inflammatory mediators (e.g. eicosanoids) and ECs,
contributing to the progression of cardiovascular diseases, diabetes, obesity,
depression or impairing conditions, such as Alzheimer' s disease. Here we review
how diets based in PUFAs might be linked to ECS and to the maintenance of central
and peripheral metabolism, brain plasticity, memory and learning, blood flow, and
genesis of neural cells.
PMID- 28686543
TI - A Physician's Attempt to Self-Medicate Bipolar Depression with N,N
Dimethyltryptamine (DMT).
AB - N,N-dimethyltryptamine (DMT) is a psychoactive substance that has been gaining
popularity in therapeutic and recreational use. This is a case of a physician who
chronically took DMT augmented with phenelzine in an attempt to self-medicate
refractory bipolar depression. His presentation of altered mental status, mania,
and psychosis is examined in regards to his DMT use. This case discusses DMT, the
possible uses of DMT, and the theorized mechanism of DMT in psychosis and
treatment of depression, particularly involving its agonist activity at 5-HT1A, 5
HT2A, and 5-HT2C. It is also important to recognize the dangers of self
medication, particularly amongst physicians.
PMID- 28686544
TI - Impact of Co-Culturing with Fractionated Carbon-Ion-Irradiated Cancer Cells on
Bystander Normal Cells and Their Progeny.
AB - The purpose of this study was to compare the biological effects of fractionated
doses versus a single dose of high-LET carbon ions in bystander normal cells, and
determine the effect on their progeny using the layered tissue co-culture system.
Briefly, confluent human glioblastoma (T98G) cells received a single dose of 6 Gy
or three daily doses of 2 Gy carbon ions, which were then seeded on top of an
insert with bystander normal skin fibroblasts (NB1RGB) growing underneath. Cells
were co-cultured for 6 h or allowed to grow for 20 population doublings, then
harvested and assayed for different end points. A single dose of carbon ions
resulted in less damage in bystander normal NB1RGB cells than the fractionated
doses. In contrast, the progeny of bystander NB1RGB cells co-cultured with T98G
cells exposed to fractionated doses showed less damage than progeny from
bystander cells co-cultured with single dose glioblastoma cells. Furthermore,
inhibition of gap junction communication demonstrated its involvement in the
stressful effects in bystander cells and their progeny. These results indicate
that dose fractionation reduced the late effect of carbon-ion exposure in the
progeny of bystander cells compared to the effect in the initial bystander cells.
PMID- 28686545
TI - The concurrent validity of the Problem Oriented Screening Instrument for
Teenagers (POSIT) substance use/abuse subscale in adolescent patients in an urban
federally qualified health center.
AB - BACKGROUND: The Problem Oriented Screening Instrument for Teenagers (POSIT)
substance use/abuse subscale has been validated with high school students,
adolescents with criminal justice involvement, and adolescent substance use
treatment samples using the Diagnostic and Statistical Manual of Mental Disorders
(DSM)-III-R and DSM-IV. This study examines the concurrent validity of the
POSIT's standard 17-item substance use/abuse subscale and a revised, shorter 11
item version using DSM-5 substance use disorder diagnoses. METHODS: Adolescents
(N = 525; 93% African American, 55% female) 12-17 years of age awaiting primary
care appointments at a Federally Qualified Health Center in Baltimore, Maryland
completed the 17-item POSIT substance use/abuse subscale and items from a
modified World Mental Health Composite International Diagnostic Interview
corresponding to DSM-5 alcohol use disorder (AUD) and cannabis use disorder
(CUD). Receiver operating characteristic curves, sensitivities, and specificities
were examined with DSM-5 AUD, CUD, and a diagnosis of either or both disorders
for the standard and revised subscales using risk cutoffs of either 1 or 2 POSIT
"yes" responses. RESULTS: For the 17-item subscale, sensitivities were generally
high using either cutoff (range: 0.79-1.00), although a cutoff of 1 was superior
(sensitivities were 1.00 for AUD, CUD, and for either disorder). Specificities
were also high using either cutoff (range: 0.81-0.95) but were higher using a
cutoff of 2. For the 11-item subscale, a cutoff of 1 yielded higher sensitivities
than a cutoff of 2 (ranges for 1 and 2: 0.96-1.00 and 0.79-0.86, respectively).
Specificities for this subscale were higher using a cutoff of 2 (ranges for 1 and
2: 0.82-0.89 and 0.89-0.96, respectively). CONCLUSIONS: Findings suggest that the
POSIT's substance use/abuse subscale is a potentially useful tool for screening
adolescents in primary care for AUD or CUD using a cutoff of 1 or 2. The briefer,
revised subscale may be preferable to the standard subscale in busy pediatric
practices.
PMID- 28686546
TI - Interaction of 17beta-estradiol and dietary fatty acids on energy and glucose
homeostasis in female mice.
AB - Fatty acid-induced hypothalamic inflammation (HI) is a potential cause of the
obesity epidemic. It is unclear whether saturated or n-6 polyunsaturated fat is
the primary driver of these effects. Premenopausal women are protected, in part,
from obesity and associated comorbidities by circulating 17beta-estradiol (E2).
It is unknown how HI interacts with E2, because most studies of HI do not examine
females despite the involvement of E2 in hypothalamic energy homeostasis. Our
objective is to determine the effects of high-fat diets with varying levels of
linoleic acid (LA) and saturated fat on the energy and glucose homeostasis in
female mice with and without E2. Female C57BL/6J mice were fed either a control
diet or a 45% kilocalories from fat diet with varying levels of LA (1, 15, or
22.5% kilocalories from LA) with or without E2 (300 MUg/kg/day orally). After 8
weeks, the oil-treated high-fat groups gained more weight than control groups
regardless of fat type. E2 reduced body fat accumulation in all high-fat groups.
Glucose clearance from glucose challenge was impaired by LA. Nighttime O2
consumption was increased by E2, regardless of diet and independent of activity.
Neuropeptides and HI genes were not affected by LA or SFA content. These data
show that fatty acid type does not affect body weight, but does affect glucose
metabolism in females, and these effects are not associated with an induction in
HI gene expression.
PMID- 28686547
TI - Incidence of Naloxone Redosing in the Age of the New Opioid Epidemic.
AB - STUDY OBJECTIVE: Naloxone, an opioid-antagonist deliverable by an intra-nasal
route, has become widely available and utilized by law enforcement officers as
well as basic life support (BLS) providers in the prehospital setting. This study
aimed to determine the frequency of repeat naloxone dosing in suspected narcotic
overdose (OD) patients and identify patient characteristics. METHODS: A
retrospective chart review of patients over 17 years of age with suspected opioid
overdose, treated with an initial intranasal (IN) dose of naloxone and
subsequently managed by paramedics, was performed from April 2014 to June 2016.
Demographic data was analyzed using descriptive statistics to identify those
aspects of the history, physical exam findings. Results: A sample size of 2166
patients with suspected opioid OD received naloxone from first responders. No
patients who achieved GCS 15 after treatment required redosing; 195 (9%) received
two doses and 53 patients received three doses of naloxone by advanced life
support. Patients were primarily male (75.4%), Caucasian (88.2%), with a mean age
of 36.4 years. A total of 76.7% of patients were found in the home, 23.1% had a
suspected mixed ingestion, and 27.2% had a previous OD. Two percent of all
patients required a third dose of naloxone. CONCLUSION: In this prehospital
study, we confirmed that intranasal naloxone is effective in reversing suspected
opioid toxicity. Nine percent of patients required two or more doses of naloxone
to achieve clinical reversal of suspected opioid toxicity. Two percent of
patients received a third dose of naloxone.
PMID- 28686548
TI - Roles of Vitamins D and K, Nutrition, and Lifestyle in Low-Energy Bone Fractures
in Children and Young Adults.
AB - The research on skeletal system health in children and young adults, while
recognizing the important role of calcium and vitamin D, goes beyond these
nutritional standards. This review focuses on the role of vitamin K in
combination with vitamin D and other factors in bone health. The current
understanding is that maintaining bone health and prevention of low-energy
fractures in any pediatric population includes nutritional factors combined with
an active lifestyle. Calcium, vitamin D, and vitamin K supplementation contribute
independently and collectively to bone health. The beneficial role of vitamin K,
particularly vitamin K2 as menaquinone-7 (MK-7), in bone and cardiovascular
health is reasonably well supported scientifically, with several preclinical,
epidemiological, and clinical studies published over the last decade. Osteocalcin
and matrix-Gla (glutamate-containing) protein (MGP) exemplify vitamin K-dependent
proteins involved in building bone matrix and keeping calcium from accumulating
in the arterial walls, respectively. An important part of the mechanism of
vitamin K involves carboxylation and posttranslational activation of the family
of vitamin K-dependent proteins, which prevent expression of pro-inflammatory
factors and support improvement in bone mineral concentration, bone mineral
density, and the quality of bone matrix. Understanding the combined approach to a
healthy skeletal system in children and young adults, including the roles of
vitamins D and K, calcium, healthy diet, and exercise, is particularly important
in view of reports of subclinical insufficiency of vitamins D and K in otherwise
healthy pediatric populations with low-energy bone fractures.
PMID- 28686549
TI - Commentary on Varban et al.: Far from Standardized: Using Surgical Videos to
Identify Variation in Technique for Laparoscopic Sleeve Gastrectomy.
PMID- 28686553
TI - Candidaemia in a tertiary care academic hospital in Italy. The impact of C.
parapsilosis complex on the species distribution and antifungal susceptibility.
AB - PURPOSE: To analyse the species distribution and the susceptibility profiles to
the major antifungal agents of Candida isolated from bloodstream infections
(BSIs) in both intensive care units (ICUs) and non-ICU wards in a tertiary care
hospital in Italy from 2010 until 2015. METHODOLOGY: Episodes of Candida BSI were
recorded in a retrospective observational cohort study. Yeasts were isolated from
both blood and intravascuIar devices (IVDs) and their susceptibility to
antifungal drugs was tested using the microdilution method. RESULTS: 514 Candida
BSIs were evidenced and 19 % of these episodes were associated with the presence
of an IVD. The trend of the general incidence increased significantly throughout
the study period, ranging from 1.42 to 3.63 (mean 2.52) episodes/1000 admissions.
The incidence of Candida BSIs and IVD-associated candidaemia was significantly
higher in ICUs relative to the other wards. The most frequently isolated species
were C. albicans and C. parapsilosis complex, with the latter presenting a
significant increased trend of isolation. C. parapsilosis complex was most
frequently involved in IVD-related candidaemia, coinfections and late recurrent
infections. Furthermore, the MIC50s of C. parapsilosis complex were significantly
enhanced for echinocandins compared to the MIC50s for the same drugs and the
other yeasts, while the MIC50s of C. albicans for amphotericin B showed a
significant increase during the study period, ranging from 0.1 to 0.5 ug ml-1.
CONCLUSIONS: A progressively enhanced incidence of Candida BSIs, a relatively
high impact of C. parapsilosis complex and changes in the susceptibility profiles
of the isolated yeasts were evidenced during the observation period.
PMID- 28686554
TI - Geographic Differences in Persistent Organic Pollutant Levels of Yellowfin Tuna.
AB - BACKGROUND: Fish are a source of persistent organic pollutants (POPs) in the
human diet. Although species, trophic level, and means of production are
typically considered in predicting fish pollutant load, and thus recommendations
of consumption, capture location is usually not accounted for. OBJECTIVES:
Yellowfin tuna (Thunnus albacares) are harvested from across the world's oceans
and are widely consumed. Here, we determined geographic variation in the overall
mass, concentration, and composition of POPs in yellowfin and examined the
differences in levels of several POP congeners of potential relevance to human
health. METHODS: We sampled dorsal muscle of 117 yellowfin tuna from 12 locations
worldwide, and measured POP levels using combined liquid or gas chromatography
and mass spectrometry according to U.S. Environmental Protection Agency standard
procedures. RESULTS: POP levels varied significantly among sites, more than 36
fold on a mass basis. Individual fish levels ranged from 0.16 to 138.29 ng/g wet
weight and lipid-normalized concentrations from 0.1 to 12.7 MUM. Levels of 10
congeners that interfere with the cellular defense protein P-glycoprotein, termed
transporter interfering compounds (TICs), ranged from 0.05 to 35.03 ng/g wet
weight and from 0.03 to 3.32 MUM in tuna lipid. Levels of TICs, and their
individual congeners, were strongly associated with the overall POP load. Risk
based analysis of several carcinogenic POPs indicated that the fish with the
highest levels of these potentially harmful compounds were clustered at specific
geographic locations. CONCLUSIONS: Capture location is an important consideration
when assessing the level and risk of human exposure to POPs through ingestion of
wild fish. https://doi.org/10.1289/EHP518.
PMID- 28686555
TI - Heat-Related Mortality in Japan after the 2011 Fukushima Disaster: An Analysis of
Potential Influence of Reduced Electricity Consumption.
AB - BACKGROUND: In March 2011, the Great East Japan Earthquake devastated several
power stations and caused severe electricity shortages. This accident was
followed by the implementation of policies to reduce summer electricity
consumption in the affected areas, for example, by limiting air-conditioning (AC)
use. This provided a natural experimental scenario to investigate if these
policies were associated with an increase in heat-related mortality. OBJECTIVES:
We examined whether the reduced electricity consumption in warm season modified
heat-related mortality from 2008 to 2012. METHODS: We conducted prefecture
specific interrupted time-series (ITS) analyses to compare temperature-mortality
associations before and after the earthquake, and used meta-analysis to generate
combined effect estimates for the most affected and less affected areas
(prefectures with >10% or <=10% reductions in electricity consumption,
respectively). We then examined whether the temperature-mortality association in
Tokyo, one of the most affected areas, was modified by the percent reduction in
electricity consumption relative to expected consumption for comparable days
before the earthquake. RESULTS: Contrary to expectations, we estimated a 5-9%
reduction in all-cause heat-related mortality after the earthquake in the 15
prefectures with the greatest reduction in electricity consumption, and little
change in the other prefectures. However, the percent reduction in observed vs.
expected daily electricity consumption after the earthquake did not significantly
modify daily heat-related mortality in Tokyo. CONCLUSIONS: In the prefectures
with the greatest reductions in electricity consumption, heat-related mortality
decreased rather than increased following the Great East Japan Earthquake.
Additional research is needed to determine whether this finding holds for other
populations and regions, and to clarify its implications for policies to reduce
the consequences of climate change on health. https://doi.org/10.1289/EHP493.
PMID- 28686556
TI - Effects of Radon and UV Exposure on Skin Cancer Mortality in Switzerland.
AB - BACKGROUND: Skin cancer incidence in Switzerland is among the highest in the
world. In addition to exposure to ultraviolet (UV) radiation, radon alpha
particles attached to aerosols can adhere to the skin and potentially cause
carcinogenic effects. OBJECTIVES: We investigated the effects of radon and UV
exposure on skin cancer mortality. METHODS: Cox proportional hazard regression
was used to study the association between exposures and skin cancer mortality in
adults from the Swiss National Cohort. Modeled radon exposure and erythemal
weighted UV dose were assigned to addresses at baseline. Effect estimates were
adjusted for sex, civil status, mother tongue, education, job position,
neighborhood socioeconomic position, and UV exposure from outdoor occupation.
RESULTS: The study included 5.2 million adults (mean age 48 y) and 2,989 skin
cancer deaths, with 1,900 indicating malignant melanoma (MM) as the primary cause
of death. Adjusted hazard ratios (HR) for MM at age 60 were 1.16 (95% CI: 1.04,
1.29) per 100 Bq/m3 radon and 1.11 (1.01, 1.23) per W/m2 in UV dose. Radon
effects decreased with age. Risk of MM death associated with residential UV
exposure was higher for individuals engaged in outdoor work with UV exposure (HR
1.94 [1.17, 3.23]), though not statistically significantly different compared to
not working outdoors (HR 1.09 [0.99, 1.21],p=0.09). CONCLUSIONS: There is
considerable variation in radon and UV exposure across Switzerland. Our study
suggests both are relevant risk factors for skin cancer mortality. A better
understanding of the role of the UV radiation and radon exposure is of high
public health relevance. https://doi.org/10.1289/EHP825.
PMID- 28686558
TI - [Psychiatric specialty training in Greece: Comparative analysis of educational
programs (2000 vs 2014)].
AB - Modern educational programs for specialization in psychiatry should follow the
developments in psychiatric science, both in the part of acquired knowledge about
mental disorders and their treatment, as well as in the part of clinical practice
in the diverse spectrum of modern psychiatric services. In Greece, the
institutional framework for psychiatric training during specialization has yet to
modernize and conform to European standards. For the moment, it is covered by a
1994 Presidential Decree, which briefly describes the time of specialization in
psychiatry and the duration of clinical practice in the relevant educational
subjects. This study presents a comparative analysis of training in the specialty
of Psychiatry in two distinct periods (2000 vs 2014). Already by the year 2000,
psychiatric training showed many structural weaknesses. The areas of clinical
experience, theoretical and psychotherapeutic training have shown wide
divergences among training centers, and limited potential for convergence with
European standards under the existing framework. Important exceptions were
certain university clinics, with the bulk of future psychiatrists in the country
falling short of educational benefits. Fifteen years later and under the burden
of the consequences of the economic crisis, the institutional framework has not
yet changed, and the overall situation seems to have deteriorated dramatically.
The number of training centers offering full specialization and the number of
psychiatrists who receive training increased in reverse proportion to the number
of specialized psychiatrists employed in hospitals, which has been drastically
reduced due to restrictive measures on staff recruitment. Almost all training
indicators show deterioration, but mainly the area of theoretical training shows
the most dramatic degradation. Nevertheless, it is noteworthy that nowadays
several psychiatric clinics endeavor to develop training programs in conjunction
with psychiatric services not under their own administration, a practice not
provided for in the current legislative framework. At the same time, there is an
increase in the number of training centers that adopt some statutory procedures
to monitor and evaluate trainees during the training process. The long-term
restrictions recorded however, reveal the difficulty hospitals and psychiatric
clinics have in developing training programs responding to the full range of
modern clinical and theoretical training in psychiatry independently and
autonomously. The recent economic crisis in the country and the attempts for much
needed administrational reforms, create now more than ever the appropriate
conditions for a reform of the educational framework for specialization in
psychiatry, taking into account national resources and future expectations for
the mental health system of our country.
PMID- 28686557
TI - The "Biopsychosocial Model": 40 years of application in Psychiatry.
AB - In 1977, the American pathologist and psychiatrist George Engel (1913-1999)
published in the Journal Science his paper "TheIn 1977, the American pathologist
and psychiatrist George Engel (1913-1999) published in the Journal Science his
paper "Theneed for a new medical model: A challenge for biomedicine", introducing
the term Biopsychosocial Model. This model basedon the results of Engel's studies
in ulcerative colitis, depression and psychogenic pain, constituted a challenge
for biomedicineand the biomedical model. The basic principles of the model
included the biological, psychological and social dimensions of the person's life
and theperception that the person suffers as a whole and not as isolated organs.
The doctor should use a holistic approach regardingillness and should consider
his/her relation with the patient socially equal. The personality and the
emotional reserves of thepatient, as well as the particular environmental
conditions in which the person lives in should be taken into account. There is no
doubt that the biopsychosocial model has established a more empathetic and
compassionate approach in medical practice. Already since 1936, the general
adaptation syndrome had been proposed by the Austrian-Canadian endocrinologist
HansSeley (1907-1982), who emphasized that psychological stressful factors may
have injurious consequences on health, while theresponse systems to stress may be
dysregulated not only by genetic factors, but also from experiences and stressful
life events,as well as by harmful behaviors such as smoking, alcohol consumption
and lack of physical exercise. Psychosocial factors may co-determine the
patient's vulnerability and the illness's severity and course. The
biopsychosocialmodel consider the interactions with genetic susceptibility,
personality, stressful events and, generally, with the patient's socialcontext.
Environmental factors increase the probability of the clinical expression of a
mental disorder, play a role in the time ofonset of an illness's manifestation,
and they can also protect a vulnerable person from the disease. Stressful
experiences modify immunological response and influence treatment compliance. Non
adherence to pharmacotherapy,as well as to the psychosocial interventions, may
cause defective recovery of psychosocial functioning, recurrence ofthe disorder,
as well as insufficient use of health resources and a higher health care cost.
The psychoeducation of patients andtheir relatives by the application of the
biopsychosocial model plays an important role in psychiatric therapeutics, and it
mayalso be used via Internet in the frame of telepsychiatry. Results from
neuroimaging studies have shown that the different kinds of human experiences,
traumatic or therapeutic, havemeasurable influences on the brain function.
Psychotherapy may modify the neuronal connections of the brain in the frame ofits
plasticity, as was found by the discovery of synaptogenesis in response to
learning and can, thus, be considered not only as astrictly psychological but
also as a biopsychosocial form of treatment. Among the disadvantages of the
biopsychosocial model have been reported the lack of a concise theoretical
frameworkregarding its function and content, that it is complicated, difficulties
in its coordination and assignment of responsibilities, aswell as problems with
the education on it being multifaceted. The biopsychosocial model has been
criticized that it does notconstitute a scientific or philosophical model, it
does not provide an answer to the crucial question of how the biological,
psychologicaland social variables interact in the disease's expression, that it
does not provide guidance on the exact time of itsapplication and, finally, that
it allows for a wide range of interventions without providing specific guidelines
of a concrete therapeutic scheme. The person-centered diagnosis is based on the
biopsychosocial model, connects science with humanism and uses all thepossible
ways so that the clinicians, the patients and their families collaborate for a
more effective management of the disease.This approach has been established by
the World Psychiatric Association (WPA, 2007) as the program "Psychiatry for the
Person". Psychiatry in everyday practice presents particularities versus other
medical disciplines due to the complexity and polymorphismPsychiatry in everyday
practice presents particularities versus other medical disciplines due to the
complexity and polymorphismof the expression of mental disorders, their close
relation to psychosocial factors, the lack of explicit pathognomonicelements and
the stigmatization of mental illness. For these reasons, the biopsychosocial
model is particularly applicable inpsychiatric disorders, but it should not be
over looked also in somatic illnesses. The biopsychosocial model, despite the
criticism it was subjected to, continues to offer valuable clinical, educational
andresearch services, as well as to provide an important contribution to the
formation of health policies, not only for psychiatry, butfor the whole of
medicine as well.
PMID- 28686559
TI - [Attenuated psychosis syndrome: A new diagnostic category for further study in
DSM-5].
AB - In recent years an increasing number of studies focus on the issue of early
diagnosis and intervention. At the same time, a large number of special service
units for early psychosis have been established around the world especially in
Australia, USA, UK, Germany etc. Recently, similar units operate in Greece also.
The Diagnostic Manual of Mental Disorders of the American Psychiatric Association
in its latest edition in 2013 (DSM-5), introduced the category "Attenuated
Psychosis Syndrome" (APS) for people with early psychotic experiences in the
section: "Conditions for further study '. This new category has specific criteria
and describes a situation, in which a person displays psychotic symptoms in an
attenuated form, with quite unaffected reality testing, but not qualifying a
diagnosis of schizophrenic spectrum. The clinical expression of APS should be
differentiated with several well known psychiatric disorders such as: brief
psychotic disorder, schizotypal personality disorder, major depression with
psychotic features, adolescence adjustment disorders, drug use, etc. The
"Attenuated Psychosis Syndrome" occurs mainly in adolescence and in young
adulthood. The mean percentage of transition to psychosis for these individuals
is estimated at 36%, three years after the onset of initial symptoms, while the
risk of transition to psychosis, although smaller, seems to remain up to ten
years later. For some other individuals, transition to other psychiatric
disorders occurs, such as depression with psychotic elements, or bipolar
disorder, while a significant number of them will not transmit to even more
serious disorders. At the biological level, studies focused in brain's
neuroimaging, suggest significant volumetric differences among people at high
risk for psychosis who later develop psychosis compared to those who don't, while
studies of psychophysiological indicators or / and genetic markers show promising
results for the identification of relevant parameters indicating the transition
to psychosis. Alphalthough an heterogeneous population, people with APS, show
significant difficulties in social, professional and cognitive level, that should
be therapeutically addressed. In an attempt to improve the clinical status of
these individuals, to delay or even to prevent a psychotic episode, a series of
interventions have been used by psychiatrists. These interventions include: (a)
administration of drugs, especially atypical antipsychotics or antidepressants in
low dosage, (b) administration of non-pharmaceutical supplements (e.g. omega-3 ),
(c) psychotherapeutic interventions, mainly cognitive behavior therapy and (d) a
combination of the above. Many questions need to be answered such as, the period
of therapeutic intervention, identification of indicators (biological or/and
clinical) that may determine the most suited for the APS individuals therapeutic
interventions or, that may foresee, to prevent the transition to psychosis. Thus,
the continuation of research in populations of APS individuals in multiple levels
is necessary.
PMID- 28686560
TI - [Hoarding Disorder in DSM-5: Clinical description and cognitive approach].
AB - Hoarding disorder is characterized by difficulty discarding or parting with
possessions regardless their actual value as well as, in most cases, persistent
acquisition of objects. Possessions are accumulated in large numbers that fill up
and clutter active living space to the extent that its intended use is no longer
possible resulting to significant functional impairment and/or distress. Saving
and difficulty discarding appear to be associated to subjective beliefs about the
instrumental, sentimental or intrinsic value of objects. Despite significant
impact on the individual, the family and the community, until recently hoarding
disorder had been a "neglected" clinical phenomenon. The recent research efforts
to study and understand this phenomenon led to significant changes regarding the
diagnostic status and therapeutic interventions. It was classified as a distinct
diagnostic entity in the recent edition of the Diagnostic and Statistical Manual
of Mental Disorders of the American Psychiatric Association-5th ed. (DSM-5).
Hoarding is not considered a symptom of obsessive compulsive disorder or
obsessive compulsive personality disorder anymore and it is now ranked among
compulsive spectrum disorders. So far the cognitive model for hoarding disorder
is the main, widely accepted, clinically and empirically supported theoretical
framework for understanding its features. The cognitive model offers an
explanation about the predisposing, onset and perpetuating factors of the
disorder as well as the basis for the development of specific therapeutic
interventions. The cognitive model conceptualizes hoarding disorder as a result
of four factors: personal vulnerability (heredity, early experiences and life
events, personality traits, interpersonal difficulties), difficulties in
information processing (deficits in attention, memory, executive functions such
as decision making and categorization), maladaptive cognitive content (meaning of
possessions, emotional attachment to possessions, dysfunctional beliefs in
relation to the mnemonic ability and memory importance) through which hoarding
behaviors are reinforced and finally installed (positive and negative
reinforcement, association with positive or negative emotions e.g. pleasure in
relation to acquisition/saving and anxiety or discomfort in relation to
discarding). The purpose of this article is to inform about this new disorder
giving emphasis on recent data in regard to its phenomenology and provide a
detailed description of the cognitive model. Finally, a brief mention on the
psychotherapeutic and pharmacological interventions is presented. Hoarding
Disorder is a difficult clinical problem to treat. Poor insight, ego-syntonic
nature of symptoms and treatment resistance are often reported in patients.
Further improvement of the therapeutic interventions in order to improve
effectiveness and target the high rate of treatment drop out is needed.
PMID- 28686561
TI - [The concept of temperament and its contribution to the understanding of the
bipolar spectrum].
AB - The present article attempts first to provide a historical overview of the
concept of temperament,The present article attempts first to provide a historical
overview of the concept of temperament,since its foundation by Polybos (4th
century B.C.) and the school of Cos, its predominant role in theshaping of the
anthropological and humanitarian sciences, until the modern theoretical
formulations,such as those proposed by Robert Cloninger and Hagop Akiskal.
Secondly, recent literature ispresented, which suggests a strong link of
different temperament structures to mental health andpsychopathology. Hans
Eysenck (1916-1997) was the first psychologist to establish approaches
topersonality differences and to distinguish three dimensions of personality:
Neuroticism, Extraversionand Psychotisism. Eysenck was followed by McCrae and
Costa who proposed that there are five basicdimensions of personality ("Big
Five"). In the mid-1980s, Robert Cloninger developed a distinctivedimensional
model of temperament and character traits. Hagop Akiskal emphasized on the
affectivecomponents of temperament and their possible connections to mood
disorders and creativity.Specifically, temperament assessment seems to help in
differentiating between the relationship ofvarious temperaments and the clinical
manifestations of bipolar illness. Within the area of mood disorders,specific
affective temperaments might constitute vulnerability factors, as well as
clinical pictureand illness course modifiers. Viewing mood disorders under this
prism gives birth to the concept ofthe bipolar spectrum with major implications
for all aspects of mental health research and providingof care. The hyperthymic
and the depressive temperaments are related to the more 'classic' bipolarpicture
(that is euphoria, grandiose and paranoid thinking, antisocial behavior,
psychomotor accelerationand reduced sleep and depressive episodes respectively).
On the contrary cyclothymic, anxiousand irritable temperaments are related to
more complex pictures and might predict poor responseto treatment, violent or
suicidal behavior and high comorbidity. Unipolar disorder diagnosis is
oftenchanged due to the fact that a manic or mixed episode can occur after
several years of treatment failure.In these cases the evaluation of temperament
can prove to be effective in distinguishing betweenunipolar and bipolar
depression and thus favoring treatment planning. In addition, temperament
assessmentchanges the definition of bipolarity by supporting the concept of
"bipolar spectrum". This isa factor that can lead to a rise in prevalence of
bipolar cases. Furthermore, the evaluation of temperamenthas shifted our
understanding of bipolarity towards the concept of the 'bipolar spectrum'. It
hasalso led to an increase in the prevalence of bipolar disorder cases, notably
bipolar II, and a decrease in unipolar cases. Finally, incorporating the concept
of temperament in our understanding of bipolardisorder constitutes a challenging
issue, which can lead to better treatment and outcome of patients.
PMID- 28686562
TI - [Impulsivity as an immediate factor between addictive disorders and Attention
Deficit-Hyperactivity Disorder].
AB - Impulsivity is a behavior in everyday life of mentally healthy individuals. But
in some cases the degree of impulsivity begins to create negative effects on
one's life and acquires pathological connotation. Two clinical entities in which
can be observed a high degree of impulsivity is Attention Deficit Hyperactivity
Disorder (ADHD) and Addictive disorders. In these disorders, both impulsive act
and impulsive choice are observed. According to some researchers, genetic factors
are involved in the control of impulsivity. The impulsive choice, in the sense of
delay discounting, may be an intermediate phenotype or endophenotype that
contributes to vulnerability with respect to specific disorders in which
impulsivity plays a central and decisive role. Another group of researchers argue
that ADHD is one of the expressions of a more generalized disorder, known as
reward-deficiency syndrome. In this syndrome, it is included increased frequency
of addictive disorders. On the other hand, some researchers argue that ADHD in
adolescence does not increase the likelihood of developing dependencies, when it
is not accompanied by comorbidity of conduct disorders. Regarding the use of
substances, there have been conflicting views in relation to etiopathogenesis of
impulsivity observed in the addicted patients and whether this impulsivity
precedes or follows the onset of substance use. The element that links ADHD with
impaired preoccupation with gambling and has been studied most is also
impulsivity. Some researchers theorize that ADHD mediates with the element of
impulsivity in the development of disordered involvement with gambling in some
patients. The positive correlation between impulsivity and addiction to gambling
arises, whether behavioral scales or questionnaires about personality have been
used. Moreover the higher measured impulsivity of the patient, the more serious
are the symptoms of dependence. Abnormalities in neurotransmitter systems have
been found both in patients with dependence on gambling, as well as in patients
with impulsive behavior. It seems that impulsivity in these players is part of
their personality and not a transient behavior. The variety of views that exists
and the debate surrounding this issue reflects the multidisciplinary nature of
the phenomenon of impulsivity, when found in dual diagnosis of Attention
Deficit/Hyperactivity Disorder and Addictive Disorder. It is important for
patients with ADHD or any form of addictive disorder, presenting for treatment,
to assess the degree of their impulsivity and to investigate the possible
comorbidity with other mental health problems, in which impulsivity plays a
central role.
PMID- 28686563
TI - [Legal capacity and instruments assessing cognitive functions in patients with
dementia].
AB - The term "legal capacity" refers to the ability of a person to make a valid
declaration of his will or to accept such a declaration. This ability constitutes
the main condition for the validity of the legal transaction. The legal
transaction includes issues that are adjusted by the Civil Code with which the
relations of the citizens in a society are regulated. General practitioners and
legal advisors, in any case of a person with cognitive impairment of various
severity, should take into account that the assessment tests of the cognitive
functions are not by themselves diagnostic of the dementia and they cannot be
used as the only way of evaluation of the capacity of patients with cognitive
impairment or possible dementia to respond to the needs of everyday life and in
more complex decisions, such as the legal capacity. The existing methods for the
assessment of the cognitive functions are valuable, mainly, for the detection of
any cognitive impairment which may not be perceptible during the clinical
evaluation of the patient and secondly for the detection of any changes in the
cognitive status of the patient during its following up. The description and
study of the instruments which are frequently used in the international
scientific society for the assessment of the cognitive functions of the patients
with mild cognitive impairment or dementia, during the evaluation of the legal
capacity of these patients. The literature relevant to the existing methods
assessing the cognitive functions during the evaluation of the legal capacity of
patients with dementia was reviewed. The scientific database searched was Pubmed,
Medline and Scopus. The key-words used were cognitive functions, dementia,
instruments, legal capacity. Various instruments which assess the cognitive
functions have been developed and can be grouped in 4 categories. The first one
includes instruments used for the general assessment of the cognitive status.
These instruments can be extensive or short and consist of subtests for the
evaluation of several cognitive functions (memory, attention, perception,
speech). The second category includes instruments for the specific assessment of
the cognitive status, namely specific tests for one cognitive domain (for
example, memory, speech flow, naming). The third category consists of methods
which are based on the clinical evaluation during the interview with the patient
and his familiars, giving emphasis on the frontal functions of the patient.
Finally, the fourth group includes instruments which assess the executive
functions of the patients. There is a great need for the development of more
studies for the methods/instruments with which the cognitive functions of
patients with probable dementia can be assessed during the evaluation of the
legal capacity of these patients. The challenge for the scientists is to develop
a clinically applicable instrument for the quick and reliable assessment of the
legal capacity of people with dementia. The assessment of this ability should be
done in relation with the needs, the feelings and the values of the patient.
PMID- 28686564
TI - Asperger syndrome and schizophrenia: Nueurodevelopmental continuum or separated
clinical entities?
AB - This article is an overview of the literature on Asperger's syndrome and
schizophrenia and aim to discuss their similarities and differences. Eugen
Bleuler who associated the terms "schizophrenia" and "autism" a century ago,
viewed autism as a form of solitude of schizophrenic patients representing
withdrawal from reality. Ever since, there has been confusion as to the
boundaries between these conditions. Nowadays recent research, from a variety of
perspectives-genomics, neurodevelopment, psychiatry, etc. has given new
information on these conditions. It is easier to demarcate these two disorders at
the extremes, but it is extremely difficult dissociating milder forms of both
disorders. Asperger's syndrome (AS), is considered to be a continuous and
lifelong disorder with strong heritability, present from early childhood. It is
included within the category of autism spectrum disorders and it is usually
diagnosed in childhood. Patients with Asperger syndrome are often diagnosed late
or they are considered as having schizophrenia. Misdiagnosing Asperger syndrome
creates severe problems by preventing effective therapy. A lot of clinical
characteristics of Asperger's syndrome are also present in schizophrenia, such as
impaired social interaction, disabilities in communication and restricted
interests. On the other side some clinical features may facilitate the
differential diagnosis, such as the younger age at onset, family history of
pervasive developmental disorders, pragmatic aspects of language use, lack of
imagination, ect. It is known that symptoms of Asperger's syndrome have some
overlap with those of schizophrenia, but less is known about comorbidity between
these two syndromes. It is still a question whether autism spectrum disorders in
young children can increase the risk for the development of schizophrenia and
other psychotic disorders, later in life. Both disorders are of
neurodevelopmental origin and genetic factors are prominent. In both
neurocognitive deficits as well as deficits in social cognition and social
functioning are marked. The boundaries between AS and schizophrenia are still not
clear even if this distinction is necessary for the appropriate treatment of the
patient and his family. For the writing of the literature review, the following
electronic databases were used: PubMed, Scopus, Psycinfo, Cochrane Library, Web
of Science and Google Scholar. The key words used were: Asperger's syndrome,
schizophrenia, children and adolescents, differential diagnosis, autism spectrum
disorders.
PMID- 28686565
TI - Integration of Ecology and Environmental Metagenomics Conceptual and
Methodological Frameworks.
AB - Although from its origin metagenomics was concerned with composition of
communities of microbial OTUs (Operational Taxonomic Units) living in a given
habitat and their diversity and functional heterogeneity (concepts already well
rooted in ecology), the new field was more 'environmentally' than 'ecologically'
oriented. Probably by circumstantial reasons, metagenomics and ecology followed
rather independent trajectories and conceptual and methodological gaps appeared.
Recently, calls for the need of integrating the theoretical basis and
methodologies coming from metagenomics (and other meta-omics) and ecology have
been made. Here I will address some of the principles and methods of field
ecology that, although useful in the context of environmental metagenomic
studies, have been rather disregarded. In particular, I will emphasize the
contribution of some well established concepts and methods of field ecology to a
an appropriate field sampling and experimental design of environmental
metagenomic studies.
PMID- 28686566
TI - Guidelines to Statistical Analysis of Microbial Composition Data Inferred from
Metagenomic Sequencing.
AB - Metagenomics, the application of high-throughput DNA sequencing for surveys of
environmental samples, has revolutionized our view on the taxonomic and genetic
composition of complex microbial communities. An enormous richness of microbiota
keeps unfolding in the context of various fields ranging from biomedicine and
food industry to geology. Primary analysis of metagenomic reads allows to infer
semi-quantitative data describing the community structure. However, such
compositional data possess statistical specific properties that are important to
be considered during preprocessing, hypothesis testing and interpreting the
results of statistical tests. Failure to account for these specifics may lead to
essentially wrong conclusions as a result of the survey. Here we present a
researcher introduced to the field of metagenomics with the basic properties of
microbial compositional data including statistical power and proposed
distribution models, perform a review of the publicly available software tools
developed specifically for such data and outline the recommendations for the
application of the methods.
PMID- 28686567
TI - Methods for The Metagenomic Data Visualization and Analysis.
AB - Surveys of environmental microbial communities using metagenomic approach produce
vast volumes of multidimensional data regarding the phylogenetic and functional
composition of the microbiota. Faced with such complex data, a metagenomic
researcher needs to select the means for data analysis properly. Data
visualization became an indispensable part of the exploratory data analysis and
serves a key to the discoveries. While the molecular-genetic analysis of even a
single bacterium presents multiple layers of data to be properly displayed and
perceived, the studies of microbiota are significantly more challenging. Here we
present a review of the state-of-art methods for the visualization of metagenomic
data in a multi-level manner: from the methods applicable to an in-depth analysis
of a single metagenome to the techniques appropriate for large-scale studies
containing hundreds of environmental samples.
PMID- 28686568
TI - Comparing Viral Metagenomic Extraction Methods.
AB - A crucial step in the molecular detection of viruses in clinical specimens is the
efficient extraction of viral nucleic acids. The total yield of viral nucleic
acid from a clinical specimen is dependent on the specimen's volume, the initial
virus concentration and the effectiveness provided by the extraction method.
Recent Next Generation Sequencing (NGS)-based diagnostic approaches (i.e.
metagenomics) provide a molecular 'open view' into the sample, as they
theoretically generate sequence reads of any nucleic acid present in a specimen
in a statistically representative manner. However, since a higher virus-related
read output promises better sensitivity in the subsequent bioinformatic analysis,
the extraction method selected determines the reliability of diagnostic NGS. In
this study nine commercially available kits for nucleic acid extraction were
compared regarding the simultaneous isolation of DNA and RNA by real-time
PCR,four of which were selected for subsequent comparison by NGS (QIAamp Viral
RNA Mini Kit, QIAamp DNA Blood Mini Kit, QIAamp cador Pathogen Mini Kit and
QIAamp MinElute Virus Spin Kit). The nucleic acid yields and the sequence read
output were compared for four different model viruses comprising Reovirus,
Orthomyxovirus, Orthopoxvirus and Paramyxovirus, each at defined but varying
concentrations in the same sample. The total amount of nucleic acid was processed
to sequence the RNA (as cDNA) and the DNA with quantification by Qubit and virus
specific quantitative real-time PCRs. NGS libraries were prepared for sequencing
on the Illumina HiSeq 1500 system. Finally, the percentage of reads assignable to
each virus was determined via mapping. Evaluation of different commercial nucleic
acid extraction kits with four different viruses indicates little variation in
the read numbers obtained for transcribed RNA or DNA by NGS. Since NGSis
increasingly being used as a tool in diagnostics of infectious diseases, the
individual steps of the complete process have to be validated carefully. Here we
could show that for virus identification in liquid clinical specimens, any
nucleic acid extraction kit that is performing well for PCR diagnostics can be
used for NGS diagnostics as well and that the selection of the kit has only a
minor impact on the yield of viral reads.
PMID- 28686569
TI - Spatio-Temporal Variations in the Abundance and Structure of Denitrifier
Communities in Sediments Differing in Nitrate Content.
AB - Spatial and temporal variations related to hydric seasonality in abundance and
diversity of denitrifier communities were examined in sediments taken from two
sites differing in nitrate concentration along a stream Donana National Park
during a 3-year study. We found a positive relationship between the relative
abundance of denitrifiers, determined as narG, napA, nirK, nirS and nosZ
denitrification genes, and sediment nitrate content, with similar spatial and
seasonal variations. However, we did not find association between denitrification
activity and the community structure of denitrifiers. Because nosZ showed the
strongest correlation with the content of nitrate in sediments, we used this gene
as a molecular marker to construct eight genomic libraries. Analysis of these
genomic libraries revealed that diversity of the nosZ-bearing communities was
higher in the site with higher nitrate content. Regardless of nitrate
concentration in the sediments, the Bradyrhizobiaceae and Rhodocyclaceae were the
most abundant families. On the contrary, Rhizobiaceae was exclusively present in
sediments with higher nitrate content. Results showed that differences in
sediment nitrate concentration affect the composition and diversityof nosZ
bearing communities.
PMID- 28686570
TI - Using Metagenomics to Connect Microbial Community Biodiversity and Functions.
AB - Microbes constitute about a third of the Earth's biomass and are composed by an
enormous genetic diversity. In a majority of environments the microbial
communities play crucial roles for the ecosystem functioning, where a drastic
biodiversity alteration or loss could lead to negative effects on the environment
and sustainability. A central goal in microbiome studies is to elucidate the
relation between microbial diversity to functions. A better understanding of the
relation diversity-function would increase the ability to manipulate that
diversity to improve plant and animal health and also setting conservation
priorities. The recent advances in genomic methodologies in microbial ecology
have provide means to assess highly complex communities in detail, making
possible the link between diversity and the functions performed by the microbes.
In this work we first explore some advances in bioinformatics tools to connect
the microbial community biodiversity to their potential metabolism and after
present some examples of how this information can be useful for a better
understanding of the microbial role in the environment.
PMID- 28686571
TI - Application of Omics Approaches to Studying Methylotrophs and Methylotroph
Comunities.
AB - This review covers some recent advances in application of omics technologies to
studying methylotrophs, with special reference to their activities in natural
environments. Some of the developments highlighted in this review are the new
outlook at the role of the XoxF-type, lanthanum-dependent methanol dehydrogenase
in natural habitats, new mechanistic details of methane oxidation through the
reverse methanogenesis pathway, propensity of 'aerobic' methanotrophs to thrive
in hypoxic environments and potential connection of this process to
denitrification, and a novel outlook at methane oxidation as a community
function.
PMID- 28686572
TI - Adolescent suicide as a global public health issue.
AB - Youth suicide is a major global mental health problem. This review looks at the
epidemiology, risk and protective factors associated with youth suicide, and
global strategies to address this important issue. To better understand factors
contributing to youth suicide, global gender differences in suicide were
examined. Global rates of suicide amongst young men are higher than young women.
However, there are anomalously higher rates of female youth suicide in India and
China, and possible causes of this are examined further. It is likely that
underestimation of youth suicide is a major factor affecting the accuracy of
suicide epidemiology. Risk factors for youth suicide are varied. Psychiatric
factors include various psychiatric illnesses, substance use (particularly
amongst refugee and homeless youth). Psychosocial risk factors include family
conflict, physical and sexual childhood abuse, isolation, socioeconomic
disadvantage, discrimination and acculturation. Vulnerable populations are at
increased risk, including refugee/immigrant/indigenous youth, those in foster
care and homeless youth. Protective factors can include family cohesion and
strong interpersonal relationships, as well as increased access to care. Global
strategies to prevent youth suicide include reducing lethal means to suicide and
reducing harmful media reporting. Various psychosocial interventions may be
helpful, including individual support, and family, school and community based
interventions. Strategies can also increase evaluation of psychiatric disorders
and access to care, as well as promote psycho-education and reduce stigma against
mental illness.
PMID- 28686573
TI - Modelling Mixed Types of Outcomes in Additive Genetic Models.
AB - We present a general statistical modelling framework for handling multivariate
mixed types of outcomes in the context of quantitative genetic analysis. The
models are based on the multivariate covariance generalized linear models, where
the matrix linear predictor is composed of an identity matrix combined with a
relatedness matrix defined by a pedigree, representing the environmental and
genetic components, respectively. We also propose a new index of heritability for
non-Gaussian data. A case study on house sparrow (Passer domesticus) population
with continuous, binomial and count outcomes is employed to motivate the new
model. Simulation of multivariate marginal models is not trivial, thus we adapt
the NORTA (Normal to anything) algorithm for simulation of multivariate
covariance generalized linear models in the context of genetic data analysis. A
simulation study is presented to assess the asymptotic properties of the
estimating function estimators for the correlation between outcomes and the new
heritability index parameters. The data set and R code are available in the
supplementary material.
PMID- 28686574
TI - Prediction of Primary Tumors in Cancers of Unknown Primary.
AB - A cancer of unknown primary (CUP) is a metastatic cancer for which standard
diagnostic tests fail to identify the location of the primary tumor. CUPs account
for 3-5% of cancer cases. Using molecular data to determine the location of the
primary tumor in such cases can help doctors make the right treatment choice and
thus improve the clinical outcome. In this paper, we present a new method for
predicting the location of the primary tumor using gene expression data: locating
cancers of unknown primary (LoCUP). The method models the data as a mixture of
normal and tumor cells and thus allows correct classification even in impure
samples, where the tumor biopsy is contaminated by a large fraction of normal
cells. We find that our method provides a significant increase in classification
accuracy (95.8% over 90.8%) on simulated low-purity metastatic samples and shows
potential on a small dataset of real metastasis samples with known origin.
PMID- 28686575
TI - Drugs for sexually transmitted infections.
PMID- 28686576
TI - A Novel Fast Mobile-Window Small Incision Technique for Hip Arthroplasty in the
Elderly and Comparison with Conventional Incision.
AB - BACKGROUND We deeloped a novel technique - fast mobile-window small incision
(FMWSI) - a modification of minimally invasive surgery for total hip
arthroplasty, which we believe is particularly suited to elderly patients with
hip fractures. The present article aimed to introduce this technique and compare
the clinical effects between the FMWSI technique and conventional incision (CI)
for hip arthroplasty in elderly patients. MATERIAL AND METHODS This study
included 240 consecutive patients who underwent hip arthroplasty. Half received
total hip arthroplasty and half received hemi hip arthroplasty. The 120 patients
in each group were further divided into FMWSI and CI groups. The following
parameters were compared between the FMWSI and CI groups: length of incision,
operation time, bleeding volume, drainage volume, postoperative ambulation time,
and Harris score. RESULTS Compared with the CI group, the FMWSI group had a
significantly shorter incision length, operation time, and postoperative
ambulation time, as well as lower bleeding and drainage volumes, irrespective of
whether the treatment was total or hemi hip arthroplasty (P<0.05). However, no
significant difference was found in the Harris score between the FMWSI and CI
groups (P>0.05). CONCLUSIONS The novel FMWSI technique introduced in this study
is a useful method for hip arthroplasty, especially for elderly patients with
poor constitutions or tolerance to surgery.
PMID- 28686577
TI - mTOR/Raptor signaling is critical for skeletogenesis in mice through the
regulation of Runx2 expression.
AB - The mammalian target of rapamycin (mTOR)/regulatory-associated protein of mTOR
(Raptor) pathway transmits and integrates different signals including growth
factors, nutrients, and energy metabolism. Nearly all these signals have been
found to play roles in skeletal biology. However, the contribution of mTOR/Raptor
to osteoblast biology in vivo remains to be elucidated as the conclusions of
recent studies are controversial. Here we report that mice with a deficiency of
either mTOR or Raptor in preosteoblasts exhibited clavicular hypoplasia and
delayed fontanelle fusion, similar to those found in human patients with
cleidocranial dysplasia (CCD) haploinsufficient for the transcription factor runt
related transcription factor 2 (Runx2) or those identified in Runx2+/- mice.
Mechanistic analysis revealed that the mTOR-Raptor-S6K1 axis regulates Runx2
expression through phosphorylation of estrogen receptor alpha, which binds to
Distal-less homeobox 5 (DLX5) and augments the activity of Runx2 enhancer.
Moreover, heterozygous mutation of raptor in osteoblasts aggravates the bone
defects observed in Runx2+/- mice, indicating a genetic interaction between
Raptor and Runx2. Collectively, these findings reveal that mTOR/Raptor signaling
is essential for bone formation in vivo through the regulation of Runx2
expression. These results also suggest that a selective mTOR/Raptor antagonist,
which has been developed for treatment of many diseases, may have the side effect
of causing bone loss.
PMID- 28686578
TI - Culling of APCs by inflammatory cell death pathways restricts TIM3 and PD-1
expression and promotes the survival of primed CD8 T cells.
AB - We evaluated the impact of premature cell death of antigen-presenting cells
(APCs) by Caspase-1- and RipK3-signaling pathways on CD8+ T-cell priming during
infection of mice with Salmonella typhimurium (ST). Our results indicate that
Caspase1 and RipK3 synergize to rapidly eliminate infected APCs, which does not
influence the initial activation of CD8+ T cells. However, the maintenance of
primed CD8+ T cells was greatly compromised when both these pathways were
disabled. Caspase-1- and RipK3-signaling did not influence NF-kappaB signaling in
APCs, but synergized to promote processing of IL-1 and IL-18. Combined deficiency
of Caspase1 and RipK3 resulted in compromised innate immunity and accelerated
host fatality due to poor processing of IL-18. In contrast, synergism in cell
death by Caspase-1- and RipK3 resulted in restriction of PD-1 and TIM3 expression
on primed CD8+ T cells, which promoted the survival of activated CD8+ T cells.
PMID- 28686579
TI - Synergy between Prkdc and Trp53 regulates stem cell proliferation and GI-ARS
after irradiation.
AB - Ionizing radiation (IR) is one of the most widely used treatments for cancer.
However, acute damage to the gastrointestinal tract or gastrointestinal acute
radiation syndrome (GI-ARS) is a major dose-limiting side effect, and the
mechanisms that underlie this remain unclear. Here we use mouse models to explore
the relative roles of DNA repair, apoptosis, and cell cycle arrest in radiation
response. IR induces DNA double strand breaks and DNA-PK mutant Prkdcscid/scid
mice are sensitive to GI-ARS due to an inability to repair these breaks. IR also
activates the tumor suppressor p53 to trigger apoptotic cell death within
intestinal crypt cells and p53 deficient mice are resistant to apoptosis. To
determine if DNA-PK and p53 interact to govern radiosensitivity, we compared the
response of single and compound mutant mice to 8 Gy IR. Compound mutant
Prkdcscid/scid/Trp53-/-mice died earliest due to severe GI-ARS. While both
Prkdcscid/scid and Prkdcscid/scid/Trp53-/-mutant mice had higher levels of IR
induced DNA damage, particularly within the stem cell compartment of the
intestinal crypt, in Prkdcscid/scid/Trp53-/-mice these damaged cells abnormally
progressed through the cell cycle resulting in mitotic cell death. This led to a
loss of Paneth cells and a failure to regenerate the differentiated epithelial
cells required for intestinal function. IR-induced apoptosis did not correlate
with radiosensitivity. Overall, these data reveal that DNA repair, mediated by
DNA-PK, and cell cycle arrest, mediated by p53, cooperate to protect the stem
cell niche after DNA damage, suggesting combination approaches to modulate both
pathways may be beneficial to reduce GI-ARS. As many cancers harbor p53
mutations, this also suggests targeting DNA-PK may be effective to enhance
sensitivity of p53 mutant tumors to radiation.
PMID- 28686580
TI - Upregulation of LYAR induces neuroblastoma cell proliferation and survival.
AB - The N-Myc oncoprotein induces neuroblastoma by regulating gene transcription and
consequently causing cell proliferation. Paradoxically, N-Myc is well known to
induce apoptosis by upregulating pro-apoptosis genes, and it is not clear how N
Myc overexpressing neuroblastoma cells escape N-Myc-mediated apoptosis. The
nuclear zinc finger protein LYAR has recently been shown to modulate gene
expression by forming a protein complex with the protein arginine
methyltransferase PRMT5. Here we showed that N-Myc upregulated LYAR gene
expression by binding to its gene promoter. Genome-wide differential gene
expression studies revealed that knocking down LYAR considerably upregulated the
expression of oxidative stress genes including CHAC1, which depletes
intracellular glutathione and induces oxidative stress. Although knocking down
LYAR expression with siRNAs induced oxidative stress, neuroblastoma cell growth
inhibition and apoptosis, co-treatment with the glutathione supplement N-acetyl-l
cysteine or co-transfection with CHAC1 siRNAs blocked the effect of LYAR siRNAs.
Importantly, high levels of LYAR gene expression in human neuroblastoma tissues
predicted poor event-free and overall survival in neuroblastoma patients,
independent of the best current markers for poor prognosis. Taken together, our
data suggest that LYAR induces proliferation and promotes survival of
neuroblastoma cells by repressing the expression of oxidative stress genes such
as CHAC1 and suppressing oxidative stress, and identify LYAR as a novel co-factor
in N-Myc oncogenesis.
PMID- 28686581
TI - Cancer imaging using surface-enhanced resonance Raman scattering nanoparticles.
AB - The unique spectral signatures and biologically inert compositions of surface
enhanced resonance Raman scattering (SERRS) nanoparticles make them promising
contrast agents for in vivo cancer imaging. Our SERRS nanoparticles consist of a
60-nm gold nanoparticle core that is encapsulated in a 15-nm-thick silica shell
wherein the resonant Raman reporter is embedded. Subtle aspects of their
preparation can shift their limit of detection by orders of magnitude. In this
protocol, we present the optimized, step-by-step procedure for generating
reproducible SERRS nanoparticles with femtomolar (10-15 M) limits of detection.
We provide ways of characterizing the optical properties of SERRS nanoparticles
using UV/VIS and Raman spectroscopy, and their physicochemical properties using
transmission electron microscopy and nanoparticle tracking analysis. We introduce
several applications of these nanoprobes for biomedical research, with a focus on
intraoperative cancer imaging via Raman imaging. A detailed account is provided
for successful i.v. administration of SERRS nanoparticles such that delineation
of cancerous lesions can be achieved in vivo and ex vivo on resected tissues
without the need for specific biomarker targeting. This straightforward, yet
comprehensive, protocol-from initial de novo gold nanoparticle synthesis to SERRS
nanoparticle contrast-enhanced preclinical Raman imaging in animal models-takes
~96 h.
PMID- 28686582
TI - Measurement of drug-target engagement in live cells by two-photon fluorescence
anisotropy imaging.
AB - The ability to directly image and quantify drug-target engagement and drug
distribution with subcellular resolution in live cells and whole organisms is a
prerequisite to establishing accurate models of the kinetics and dynamics of drug
action. Such methods would thus have far-reaching applications in drug
development and molecular pharmacology. We recently presented one such technique
based on fluorescence anisotropy, a spectroscopic method based on polarization
light analysis and capable of measuring the binding interaction between
molecules. Our technique allows the direct characterization of target engagement
of fluorescently labeled drugs, using fluorophores with a fluorescence lifetime
larger than the rotational correlation of the bound complex. Here we describe an
optimized protocol for simultaneous dual-channel two-photon fluorescence
anisotropy microscopy acquisition to perform drug-target measurements. We also
provide the necessary software to implement stream processing to visualize images
and to calculate quantitative parameters. The assembly and characterization part
of the protocol can be implemented in 1 d. Sample preparation, characterization
and imaging of drug binding can be completed in 2 d. Although currently adapted
to an Olympus FV1000MPE microscope, the protocol can be extended to other
commercial or custom-built microscopes.
PMID- 28686583
TI - Interfacing 3D magnetic twisting cytometry with confocal fluorescence microscopy
to image force responses in living cells.
AB - Cells and tissues can undergo a variety of biological and structural changes in
response to mechanical forces. Only a few existing techniques are available for
quantification of structural changes at high resolution in response to forces
applied along different directions. 3D-magnetic twisting cytometry (3D-MTC) is a
technique for applying local mechanical stresses to living cells. Here we
describe a protocol for interfacing 3D-MTC with confocal fluorescence microscopy.
In 3D-MTC, ferromagnetic beads are bound to the cell surface via surface
receptors, followed by their magnetization in any desired direction. A magnetic
twisting field in a different direction is then applied to generate rotational
shear stresses in any desired direction. This protocol describes how to combine
magnetic-field-induced mechanical stimulation with confocal fluorescence
microscopy and provides an optional extension for super-resolution imaging using
stimulated emission depletion (STED) nanoscopy. This technology allows for rapid
real-time acquisition of a living cell's mechanical responses to forces via
specific receptors and for quantifying structural and biochemical changes in the
same cell using confocal fluorescence microscopy or STED. The integrated 3D-MTC
microscopy platform takes ~20 d to construct, and the experimental procedures
require ~4 d when carried out by a life sciences graduate student.
PMID- 28686584
TI - Assessing recent and remote associative olfactory memory in rats using the social
transmission of food preference paradigm.
AB - Rats have the ability to learn about potential food sources by sampling their
odors on the breath of conspecifics. Although this ethologically based social
behavior has been transposed to the laboratory to probe nonspatial associative
olfactory memory, only a few studies have taken full advantage of its unique
features to examine the organization of recently and remotely acquired
information. We provide a set of standardized procedures and technical
refinements that are particularly useful in achieving this goal while minimizing
confounding factors. These procedures, built upon a three-stage protocol (odor
exposure, social interaction and preference test), are designed to optimize
performance across variable retention delays, thus enabling the reliable
assessment of recent and remote memory, and underlying processes, including
encoding, consolidation, retrieval and forgetting. The different variants of the
social transmission of food preference paradigm, which take a few days to several
weeks to perform, make it an attractive and versatile tool that can be coupled to
many applications in CNS research. The paradigm can be easily implemented in a
typical rodent facility by personnel with standard animal behavioral expertise.
PMID- 28686585
TI - Constructing cellular niche properties by localized presentation of Wnt proteins
on synthetic surfaces.
AB - Wnt signaling is crucial during embryonic development and for the maintenance of
adult tissues. Depending on the tissue type, the Wnt pathway can promote stem
cell self-renewal and/or direct lineage commitment. Wnt proteins are subject to
lipid modification, often restricting them to act in a localized manner on
responsive cells. Most methods for inducing Wnt signaling in stem cell cultures
do not control the spatial presentation of the protein. To recreate the local
presentation of Wnt proteins often seen in vivo, we previously developed a method
to immobilize the protein onto synthetic surfaces. Here we describe a detailed
protocol based on covalent binding of nucleophilic groups on Wnt proteins to
activated carboxylic acid (COOH) or glutaraldehyde (COH) groups functionalized on
synthetic surfaces. As an example, we describe how this method can be used to
covalently immobilize Wnt3a proteins on microbeads or a glass surface. This
procedure requires ~3 h and allows for the hydrophobic protein to be stored in
the absence of detergent. The immobilization efficiency of active Wnt proteins
can be assessed using different T-cell factor (TCF) reporter assays as a readout
for Wnt/beta-catenin-dependent transcription. Immobilization efficiency can be
measured 12-18 h after seeding the cells and takes 2-4 h. The covalent
immobilization of Wnt proteins can also be used for single-cell analysis using
Wnt-coated microbeads (12-18 h of live imaging) and to create a Wnt platform on a
glass surface for stem cell maintenance and cell population analysis (3 d). The
simple chemistry used for Wnt immobilization allows for adaptation to new
materials and other developmental signals. Therefore, this method can also be
incorporated into tissue engineering platforms in which depletion of the stem
cell pool restricts the complexity and maturity of the tissue developed.
PMID- 28686586
TI - Quantifying transcription factor-DNA binding in single cells in vivo with
photoactivatable fluorescence correlation spectroscopy.
AB - Probing transcription factor (TF)-DNA interactions remains challenging in complex
in vivo systems such as mammalian embryos, especially when TF copy numbers and
fluorescence background are high. To address this difficulty, fluorescence
correlation spectroscopy (FCS) can be combined with the use of photoactivatable
fluorescent proteins to achieve selective photoactivation of a subset of tagged
TF molecules. This approach, termed paFCS, enables FCS measurements within single
cell nuclei inside live embryos, and obtains autocorrelation data of a quality
previously only attainable in simpler in vitro cell culture systems. Here, we
present a protocol demonstrating the applicability of paFCS in developing mouse
embryos by outlining its implementation on a commercial laser-scanning
microscope. We also provide procedures for optimizing the photoactivation and
acquisition parameters and determining key parameters describing TF-DNA binding.
The entire procedure can be performed within ~2 d (excluding embryo culture
time), although the acquisition of each paFCS data set takes only ~10 min. This
protocol can be used to noninvasively reveal cell-to-cell variation in TF
dynamics, as well as critical, fate-predicting changes over the course of early
embryonic development.
PMID- 28686587
TI - qMotor, a set of rules for sensitive, robust and quantitative measurement of
motor performance in mice.
AB - Phenotypic analysis of mouse models of human diseases is essential to
understanding the underlying disease mechanisms and to developing therapeutics.
Many models of neurodegenerative diseases are associated with motor dysfunction,
a powerful readout for the disease. We describe here a set of measures to
quantitatively monitor early disease onset and progression. We named this set of
rules qMotor because it enables sensitive, robust and quantitative measurement of
motor performance in 3 d. qMotor can be used to assess early disease onset,
before paralysis, as well as disease progression in diverse mouse models, and can
be exploited to define robust and humane experimental end points, thereby
reducing animal suffering. As an example, we apply qMotor to SOD1G93A transgenic
mice. Early studies with the original transgenic SOD1G93A mice in the hybrid
background (B6SJL-Tg(SOD1-G93A) have been criticized because of high noise in
this mixed background and because of inadequate study designs. We applied qMotor
in SOD1G93A transgenic mice in an inbred C57BL/6J background, hereafter called
iSOD1G93A mice, and show a remarkably robust and consistent phenotype in this
line that we use to evaluate a therapeutic approach. qMotor is a protocol
generically applicable to different mouse models.
PMID- 28686588
TI - Inherent limitations of probabilistic models for protein-DNA binding specificity.
AB - The specificities of transcription factors are most commonly represented with
probabilistic models. These models provide a probability for each base occurring
at each position within the binding site and the positions are assumed to
contribute independently. The model is simple and intuitive and is the basis for
many motif discovery algorithms. However, the model also has inherent limitations
that prevent it from accurately representing true binding probabilities,
especially for the highest affinity sites under conditions of high protein
concentration. The limitations are not due to the assumption of independence
between positions but rather are caused by the non-linear relationship between
binding affinity and binding probability and the fact that independent
normalization at each position skews the site probabilities. Generally
probabilistic models are reasonably good approximations, but new high-throughput
methods allow for biophysical models with increased accuracy that should be used
whenever possible.
PMID- 28686589
TI - The sero-epidemiology of Rift Valley fever in people in the Lake Victoria Basin
of western Kenya.
AB - Rift Valley fever virus (RVFV) is a zoonotic arbovirus affecting livestock and
people. This study was conducted in western Kenya where RVFV outbreaks have not
previously been reported. The aims were to document the seroprevalence and risk
factors for RVFV antibodies in a community-based sample from western Kenya and
compare this with slaughterhouse workers in the same region who are considered a
high-risk group for RVFV exposure. The study was conducted in western Kenya
between July 2010 and November 2012. Individuals were recruited from randomly
selected homesteads and a census of slaughterhouses. Structured questionnaire
tools were used to collect information on demographic data, health, and risk
factors for zoonotic disease exposure. Indirect ELISA on serum samples determined
seropositivity to RVFV. Risk factor analysis for RVFV seropositivity was
conducted using multi-level logistic regression. A total of 1861 individuals were
sampled in 384 homesteads. The seroprevalence of RVFV in the community was 0.8%
(95% CI 0.5-1.3). The variables significantly associated with RVFV seropositivity
in the community were increasing age (OR 1.2; 95% CI 1.1-1.4, p<0.001), and
slaughtering cattle at the homestead (OR 3.3; 95% CI 1.0-10.5, p = 0.047). A
total of 553 slaughterhouse workers were sampled in 84 ruminant slaughterhouses.
The seroprevalence of RVFV in slaughterhouse workers was 2.5% (95% CI 1.5-4.2).
Being the slaughterman, the person who cuts the animal's throat (OR 3.5; 95% CI
1.0-12.1, p = 0.047), was significantly associated with RVFV seropositivity. This
study investigated and compared the epidemiology of RVFV between community
members and slaughterhouse workers in western Kenya. The data demonstrate that
slaughtering animals is a risk factor for RVFV seropositivity and that
slaughterhouse workers are a high-risk group for RVFV seropositivity in this
environment. These risk factors have been previously reported in other studies
providing further evidence for RVFV circulation in western Kenya.
PMID- 28686590
TI - Effectiveness of dasabuvir/ombitasvir/paritaprevir/ritonavir for hepatitis C
virus in clinical practice: A population-based observational study.
AB - BACKGROUND: Direct acting antivirals for hepatitis C virus have shown dramatic
results in clinical trials. However, their effectiveness has yet to be
demonstrated within observational cohorts which lack exclusion criteria found in
randomized control trials. AIM: To determine the effectiveness of
dasabuvir/ombitasvir/paritaprevir/ritonavir in achieving sustained virological
response. METHODS: Retrospective observational cohort study of all Clalit Health
Services members with hepatitis C virus genotype 1 who were dispensed
dasabuvir/ombitasvir/paritaprevir/ritonavir from January 1, 2015 to-November 31,
2015. RESULTS: There were 564 participants during the study period. The average
age was 61.9 years, 52.0% were male, and 61.5% were born Eastern/Central Europe
or Central Asia. The prevalence of diabetes was 31.7% and 70.3% were
overweight/obese. Cirrhosis was present in 41.0% of participants, of whom 52.8%
had stage 4 fibrosis. Of the cohort, 416 (74.8%) had follow-up viral load testing
at 10 or more weeks after the end of treatment. We report a sustained virological
response of 98.8% among those tested. CONCLUSIONS: Treatment with
dasabuvir/ombitasvir/paritaprevir/ritonavir demonstrated a near universal
effectiveness in achieving a sustained virological response among HCV patients in
a large cohort.
PMID- 28686592
TI - Can cerebellar and brainstem apparent diffusion coefficient (ADC) values predict
neuromotor outcome in term neonates with hypoxic-ischemic encephalopathy (HIE)
treated with hypothermia?
AB - BACKGROUND AND PURPOSE: To determine the apparent diffusion coefficient (ADC) in
specific infratentorial brain structures during the first week of life and its
relation with neuromotor outcome for Hypoxic-ischemic encephalopathy (HIE) in
term neonates with and without whole-body hypothermia (TH). MATERIALS AND
METHODS: We retrospectively evaluated 45 MRI studies performed in the first week
of life of term neonates born between 2010 and 2013 at Boston Children's
Hospital. Selected cases were classified into three groups: 1) HIE neonates who
underwent TH, 2) HIE normothermics (TN), and 3) controls. The neuromotor outcome
was categorized as normal, abnormal and death. The ADCmean was calculated for six
infratentorial brain regions. RESULTS: A total of 45 infants were included: 28
HIE TH treated, 8 HIE TN, and 9 controls. The mean gestational age was 39 weeks;
57.8% were male; 11.1% were non-survivors. The median age at MRI was 3 days
(interquartile range, 1-4 days). A statistically significant relationship was
shown between motor outcome or death and the ADCmean in the vermis (P = 0.002),
cerebellar left hemisphere (P = 0.002), midbrain (P = 0.009), pons (P = 0.014)
and medulla (P = 0.005). In patients treated with TH, the ADC mean remained
significantly lower than that in the controls only in the hemispheres (P = 0.01).
In comparison with abnormal motor outcome, ADCmean was lowest in the left
hemisphere (P = 0.003), vermis (P = 0.003), pons (P = 0.0036) and medulla (P =
0.008) in case of death. CONCLUSION: ADCmean values during the first week of life
in the left hemisphere, vermis, pons and medulla are related to motor outcome or
death in infants with HIE either with or without hypothermic therapy. Therefore,
this objective tool can be assessed prospectively to determine if it can be used
to establish prognosis in the first week of life, particularly in severe cases of
HIE.
PMID- 28686591
TI - The contribution of two isozymes to the pyruvate kinase activity of Vibrio
cholerae: One K+-dependent constitutively active and another K+-independent with
essential allosteric activation.
AB - In a previous phylogenetic study of the family of pyruvate kinase EC (2.7.1.40),
a cluster with Glu117 and another with Lys117 were found (numbered according to
the rabbit muscle enzyme). The sequences with Glu117 have been found to be K+
dependent, whereas those with Lys117 were K+-independent. Interestingly, only
gamma-proteobacteria exhibit sequences in both branches of the tree. In this
context, it was explored whether these phylogenetically distinct pyruvate kinases
were both expressed and contribute to the pyruvate kinase activity in Vibrio
cholerae. The main findings of this work showed that the isozyme with Glu117 is
an active K+-dependent enzyme. At the same substrate concentration, its Vmax in
the absence of fructose 1,6 bisphosphate was 80% of that with its effector. This
result is in accordance with the non-essential activation described by allosteric
ligands for most pyruvate kinases. In contrast, the pyruvate kinase with Lys117
was a K+-independent enzyme displaying an allosteric activation by ribose 5
phosphate. At the same substrate concentration, its activity without the effector
was 0.5% of the one obtained in the presence of ribose 5-phosphate, indicating
that this sugar monophosphate is a strong activator of this enzyme. This absolute
allosteric dependence is a novel feature of pyruvate kinase activity.
Interestingly, in the K+-independent enzyme, Mn2+ may "mimic" the allosteric
effect of Rib 5-P. Despite their different allosteric behavior, both isozymes
display a rapid equilibrium random order kinetic mechanism. The intracellular
concentrations of fructose 1,6-bisphosphate and ribose 5-phosphate in Vibrio
cholerae have been experimentally verified to be sufficient to induce maximal
activation of both enzymes. In addition, Western blot analysis indicated that
both enzymes were co-expressed. Therefore, it is concluded that VcIPK and VcIIPK
contribute to the activity of pyruvate kinase in this gamma-proteobacterium.
PMID- 28686593
TI - The proximal experience of gratitude.
AB - Although a great deal of research has tested the longitudinal effects of
regularly practicing gratitude, much less attention has been paid to the
emotional landscape directly following engagement in gratitude exercises. In
three studies, we explored the array of discrete emotions people experience after
being prompted to express or recall gratitude. In Studies 1 and 2, two different
gratitude exercises produced not only greater feelings of gratitude relative to
two positive emotion control conditions (i.e., recalling relief), but also higher
levels of other socially relevant states like elevation, connectedness, and
indebtedness. In a third study, conducted in both the U.S. and S. Korea, we
compared a gratitude exercise to another positive emotion elicitation (i.e.,
recalling a kind act) and to a neutral task, and again found that the gratitude
exercise prompted greater gratitude, elevation, indebtedness, and guilt, but no
more embarrassment or shame, than the two comparison conditions. Additionally, in
all three studies, emodiversity and cluster analyses revealed that gratitude
exercises led to the simultaneous experience of both pleasant and unpleasant
socially-relevant states. In sum, although it may seem obvious that gratitude
exercises would evoke grateful, positive states, a meta-analysis of our three
studies revealed that gratitude exercises actually elicit a mixed emotional
experience-one that simultaneously leads individuals to feel uplifted and
indebted.
PMID- 28686594
TI - Cannabinoids disrupt memory encoding by functionally isolating hippocampal CA1
from CA3.
AB - Much of the research on cannabinoids (CBs) has focused on their effects at the
molecular and synaptic level. However, the effects of CBs on the dynamics of
neural circuits remains poorly understood. This study aims to disentangle the
effects of CBs on the functional dynamics of the hippocampal Schaffer collateral
synapse by using data-driven nonparametric modeling. Multi-unit activity was
recorded from rats doing an working memory task in control sessions and under the
influence of exogenously administered tetrahydrocannabinol (THC), the primary CB
found in marijuana. It was found that THC left firing rate unaltered and only
slightly reduced theta oscillations. Multivariate autoregressive models,
estimated from spontaneous spiking activity, were then used to describe the
dynamical transformation from CA3 to CA1. They revealed that THC served to
functionally isolate CA1 from CA3 by reducing feedforward excitation and theta
information flow. The functional isolation was compensated by increased feedback
excitation within CA1, thus leading to unaltered firing rates. Finally, both of
these effects were shown to be correlated with memory impairments in the working
memory task. By elucidating the circuit mechanisms of CBs, these results help
close the gap in knowledge between the cellular and behavioral effects of CBs.
PMID- 28686595
TI - The effectiveness of celebrities in conservation marketing.
AB - Celebrities are frequently used in conservation marketing as a tool to raise
awareness, generate funding and effect behaviour change. The importance of
evaluating effectiveness is widely recognised in both marketing and conservation
but, to date, little research into the effectiveness of celebrity endorsement as
a tool for conservation marketing has been published. Using a combination of
interviews and an online choice survey instrument, we investigated the extent to
which a sample of UK-based conservation organisations, and other charities,
evaluate their own usage of celebrity endorsement, and then carried out an
experimental evaluation of a hypothetical marketing campaign. This experiment
compared participants' willingness-to-engage (WTE) with, and recall of, a
conservation message presented in versions of an advert featuring one of three
prominent UK celebrities (David Beckham, Chris Packham or HRH Prince William) or
a non-celebrity control treatment (featuring Crawford Allan, a director of
TRAFFIC USA). We find that the organisations we interviewed did not routinely
evaluate their marketing campaigns featuring celebrities. Furthermore, our
experiment provides evidence that celebrity endorsement can produce both positive
and negative effects. Participants were more willing to engage when presented
with an advert featuring one of the three celebrities than the non-celebrity
control, and WTE varied according to the characteristics of the celebrity and the
respondent. However, celebrities were less effective at generating campaign
message recall than non-celebrities. These findings suggest that celebrity
endorsement should be used carefully. Further work is required to fully
understand the role celebrity endorsers can play in conservation but, drawing on
best practice from the field of marketing, this study introduces an approach to
evaluation which could be applied more widely to improve the effectiveness of
conservation marketing.
PMID- 28686596
TI - Genetic control of the root system in rice under normal and drought stress
conditions by genome-wide association study.
AB - A variety of adverse conditions including drought stress severely affect rice
production. Root system plays a critical role in drought avoidance, which is one
of the major mechanisms of drought resistance. In this study, we adopted genome
wide association study (GWAS) to dissect the genetic basis controlling various
root traits by using a natural population consisting of 529 representative rice
accessions. A total of 413 suggestive associations, containing 143 significant
associations, were identified for 21 root traits, such as maximum root length,
root volume, and root dry weight under normal and drought stress conditions at
the maturation stage. More than 80 percent of the suggestive loci were located in
the region of reported QTLs for root traits, while about 20 percent of suggestive
loci were novel loci detected in this study. Besides, 11 reported root-related
genes, including DRO1, WOX11, and OsPID, were found to co-locate with the
association loci. We further proved that the association results can facilitate
the efficient identification of causal genes for root traits by the two case
studies of Nal1 and OsJAZ1. These loci and their candidate causal genes provide
an important basis for the genetic improvement of root traits and drought
resistance.
PMID- 28686597
TI - Altered paracellular cation permeability due to a rare CLDN10B variant causes
anhidrosis and kidney damage.
AB - Claudins constitute the major component of tight junctions and regulate
paracellular permeability of epithelia. Claudin-10 occurs in two major isoforms
that form paracellular channels with ion selectivity. We report on two families
segregating an autosomal recessive disorder characterized by generalized
anhidrosis, severe heat intolerance and mild kidney failure. All affected
individuals carry a rare homozygous missense mutation c.144C>G, p.(N48K) specific
for the claudin-10b isoform. Immunostaining of sweat glands from patients
suggested that the disease is associated with reduced levels of claudin-10b in
the plasma membranes and in canaliculi of the secretory portion. Expression of
claudin-10b N48K in a 3D cell model of sweat secretion indicated perturbed
paracellular Na+ transport. Analysis of paracellular permeability revealed that
claudin-10b N48K maintained cation over anion selectivity but with a reduced
general ion conductance. Furthermore, freeze fracture electron microscopy showed
that claudin-10b N48K was associated with impaired tight junction strand
formation and altered cis-oligomer formation. These data suggest that claudin-10b
N48K causes anhidrosis and our findings are consistent with a combined effect
from perturbed TJ function and increased degradation of claudin-10b N48K in the
sweat glands. Furthermore, affected individuals present with Mg2+ retention,
secondary hyperparathyroidism and mild kidney failure that suggest a disturbed
reabsorption of cations in the kidneys. These renal-derived features recapitulate
several phenotypic aspects detected in mice with kidney specific loss of both
claudin-10 isoforms. Our study adds to the spectrum of phenotypes caused by tight
junction proteins and demonstrates a pivotal role for claudin-10b in maintaining
paracellular Na+ permeability for sweat production and kidney function.
PMID- 28686598
TI - Processing closely spaced lesions during Nucleotide Excision Repair triggers
mutagenesis in E. coli.
AB - It is generally assumed that most point mutations are fixed when damage
containing template DNA undergoes replication, either right at the fork or behind
the fork during gap filling. Here we provide genetic evidence for a pathway,
dependent on Nucleotide Excision Repair, that induces mutations when processing
closely spaced lesions. This pathway, referred to as Nucleotide Excision Repair
induced Mutagenesis (NERiM), exhibits several characteristics distinct from
mutations that occur within the course of replication: i) following UV
irradiation, NER-induced mutations are fixed much more rapidly (t 1/2 ~ 30 min)
than replication dependent mutations (t 1/2 ~ 80-100 min) ii) NERiM specifically
requires DNA Pol IV in addition to Pol V iii) NERiM exhibits a two-hit dose
response curve that suggests processing of closely spaced lesions. A mathematical
model let us define the geometry (infer the structure) of the toxic intermediate
as being formed when NER incises a lesion that resides in close proximity of
another lesion in the complementary strand. This critical NER intermediate
requires Pol IV / Pol II for repair, it is either lethal if left unrepaired or
mutation-prone when repaired. Finally, NERiM is found to operate in stationary
phase cells providing an intriguing possibility for ongoing evolution in the
absence of replication.
PMID- 28686599
TI - Flux balance analysis predicts Warburg-like effects of mouse hepatocyte deficient
in miR-122a.
AB - The liver is a vital organ involving in various major metabolic functions in
human body. MicroRNA-122 (miR-122) plays an important role in the regulation of
liver metabolism, but its intrinsic physiological functions require further
clarification. This study integrated the genome-scale metabolic model of
hepatocytes and mouse experimental data with germline deletion of Mir122a
(Mir122a-/-) to infer Warburg-like effects. Elevated expression of MiR-122a
target genes in Mir122a-/-mice, especially those encoding for metabolic enzymes,
was applied to analyze the flux distributions of the genome-scale metabolic model
in normal and deficient states. By definition of the similarity ratio, we
compared the flux fold change of the genome-scale metabolic model computational
results and metabolomic profiling data measured through a liquid-chromatography
with mass spectrometer, respectively, for hepatocytes of 2-month-old mice in
normal and deficient states. The Ddc gene demonstrated the highest similarity
ratio of 95% to the biological hypothesis of the Warburg effect, and similarity
of 75% to the experimental observation. We also used 2, 6, and 11 months of mir
122 knockout mice liver cell to examined the expression pattern of DDC in the
knockout mice livers to show upregulated profiles of DDC from the data.
Furthermore, through a bioinformatics (LINCS program) prediction, BTK inhibitors
and withaferin A could downregulate DDC expression, suggesting that such drugs
could potentially alter the early events of metabolomics of liver cancer cells.
PMID- 28686600
TI - Analysis of Corynebacterium diphtheriae macrophage interaction: Dispensability of
corynomycolic acids for inhibition of phagolysosome maturation and identification
of a new gene involved in synthesis of the corynomycolic acid layer.
AB - Corynebacterium diphtheriae is the causative agent of diphtheria, a toxin
mediated disease of upper respiratory tract, which can be fatal. As a member of
the CMNR group, C. diphtheriae is closely related to members of the genera
Mycobacterium, Nocardia and Rhodococcus. Almost all members of these genera
comprise an outer membrane layer of mycolic acids, which is assumed to influence
host-pathogen interactions. In this study, three different C. diphtheriae strains
were investigated in respect to their interaction with phagocytic murine and
human cells and the invertebrate infection model Caenorhabditis elegans. Our
results indicate that C. diphtheriae is able to delay phagolysosome maturation
after internalization in murine and human cell lines. This effect is independent
of the presence of mycolic acids, as one of the strains lacked corynomycolates.
In addition, analyses of NF-kappaB induction revealed a mycolate-independent
mechanism and hint to detrimental effects of the different strains tested on the
phagocytic cells. Bioinformatics analyses carried out to elucidate the reason for
the lack of mycolates in one of the strains led to the identification of a new
gene involved in mycomembrane formation in C. diphtheriae.
PMID- 28686601
TI - Maternal and neonatal vitamin D status, genotype and childhood celiac disease.
AB - BACKGROUND: Low concentration of 25-hydroxyvitamin D during pregnancy may be
associated with offspring autoimmune disorders. Little is known about
environmental triggers except gluten for celiac disease, a common immune-mediated
disorder where seasonality of birth has been reported as a risk factor. We
therefore aimed to test whether low maternal and neonatal 25-hydroxyvitamin D
predicted higher risk of childhood celiac disease. METHODS AND FINDINGS: In this
Norwegian nationwide pregnancy cohort (n = 113,053) and nested case-control
study, we analyzed 25-hydroxyvitamin D in maternal blood from mid-pregnancy,
postpartum and cord plasma of 416 children who developed celiac disease and 570
randomly selected controls. Mothers and children were genotyped for established
celiac disease and vitamin D metabolism variants. We used mixed linear regression
models and logistic regression to study associations. There was no significant
difference in average 25-hydroxyvitamin D between cases and controls (63.1 and
62.1 nmol/l, respectively, p = 0.28), and no significant linear trend (adjusted
odds ratio per 10 nM increase 1.05, 95% CI: 0.93-1.17). Results were similar when
analyzing the mid-pregnancy, postpartum or cord plasma separately. Genetic
variants for vitamin D deficiency were not associated with celiac disease (odds
ratio per risk allele of the child, 1.00; 95% CI, 0.90 to 1.10, odds ratio per
risk allele of the mother 0.94; 95% CI 0.85 to 1.04). Vitamin D intake in
pregnancy or by the child in early life did not predict later celiac disease.
Adjustment for established genetic risk markers for celiac disease gave similar
results. CONCLUSIONS: We found no support for the hypothesis that maternal or
neonatal vitamin D status is related to the risk of childhood celiac disease.
PMID- 28686602
TI - Body weight concerns: Cross-national study and identification of factors related
to eating disorders.
AB - BACKGROUND: Body weight concerns are common among individuals with eating
disorders, and this construct can be assessed using psychometric instruments. The
Weight Concerns Scale (WCS) is commonly used to assess body weight concerns.
AIMS: To evaluate the psychometric properties of the WCS with Brazilian,
Portuguese, and Mozambican female college students; to estimate body weight
concerns; and to identify factors related to eating disorders. METHODS:
Confirmatory factor analysis was performed. Factorial, convergent, concurrent,
and divergent validity, as well as reliability, were assessed. Cross-national
invariance was tested by means of multigroup analysis. Structural models were
tested using the WCS as the dependent variable, while demographic and academic
variables and body mass index were used as independent variables. Logistic models
were tested to estimate the likelihood of eating disorders being developed in
specific groups. RESULTS: Participants were 2,068 female students. The
psychometric properties of the WCS were adequate for the Portuguese sample;
however, for the Brazilian and Mozambican samples, it was necessary to correlate
the errors of two items to improve model fit. The WCS did not show cross-national
invariance. The variables "thoughts about dropping out of college," "medication
use because of studies," "medication and supplements use for body change," "body
mass index," "socioeconomic status," "age," and "performance in course" were
significant predictors of body weight concerns. Overall, 24.4% (95% confidence
interval = 22.9-26.7) of the students were likely to develop eating disorders.
Students under 21 years old, who use medication and supplements for body change,
and who were classified as overweight/obese have increased likelihood of
developing eating disorders. CONCLUSION: The WCS showed good psychometric
properties with Brazilian, Portuguese, and Mozambican students; however, it did
not show cross-national invariance. We identified important aspects for
investigating body weight concerns and factors related to eating disorders.
PMID- 28686604
TI - Boosting efferocytosis in alveolar space using BCG vaccine to protect host
against influenza pneumonia.
AB - Efferocytosis by alveolar phagocytes (APs) is pivotal in maintenance of lung
homeostasis. Increased efferocytosis by APs results in protection against lethal
acute lung injury due to pulmonary infections whereas defective efferocytosis by
APs results in chronic lung inflammation. In this report, we show that pulmonary
delivery of Bacillus Calmette-Guerin (BCG) significantly enhances efferocytosis
by APs. Increased efferocytosis by APs maintains lung homeostasis and protects
mice against lethal influenza pneumonia. Intranasally treated wild type C57Bl/6
(WT) mice with BCG showed significant increase in APs efferocytosis in vivo
compared to their PBS-treated counterparts. All BCG-treated WT mice survived
lethal influenza A virus (IAV) infection whereas all PBS-treated mice succumbed.
BCG-induced resistance was abrogated by depleting AP prior to IAV infection. BCG
treatment increased uptake, and digestion/removal of apoptotic cells by APs. BCG
significantly increased the expression of TIM4 on APs and increased expression of
Rab5 and Rab7. We demonstrated that increased efferocytosis by APs through
pulmonary delivery of BCG initiated rapid clearance of apoptotic cells from the
alveolar space, maintained lung homeostasis, reduced inflammation and protected
host against lethal IAV pneumonia.
PMID- 28686603
TI - Association between elder abuse and poor sleep: A cross-sectional study among
rural older Malaysians.
AB - OBJECTIVES: To examine the association between elder abuse and poor sleep using a
Malay validated version of Pittsburgh Sleep Quality Index (PSQI). DESIGN: This
study was divided into two phases. Phase I tested the construct validity and
reliability of the Malay version of PSQI. Phase II was a population-based, cross
sectional study with a multi-stage cluster sampling method. Home-based interviews
were conducted by trained personnel using a structured questionnaire, to
determine exposure and outcome. SETTING: Kuala Pilah, a district in Negeri
Sembilan which is one of the fourteen states in Malaysia. PARTICIPANTS: 1648
community-dwelling older Malaysians. RESULTS: The Malay version of PSQI had
significant test re-test reliability with intra-class correlation coefficients of
0.62. Confirmatory factor analyses revealed that one factor PSQI scale with three
components (subjective sleep quality, sleep latency, and sleep disturbances) was
most suitable. Cronbach's Alpha was 0.60 and composite reliability was 0.63. PSQI
scores were highest among neglect (4.11), followed by physical (4.10),
psychological (3.96) and financial abuse (3.60). There was a dose-response
relationship between clustering of abuse and PSQI scores; 3.41, 3.50 and 3.84 for
"no abuse", "1 type of abuse" and "2 types or more". Generalized linear models
revealed six variables as significant determinants of sleep quality-abuse, co
morbidities, self-rated health, income, social support and gait speed. Among
abuse subtypes, only neglect was significantly associated with poor sleep.
CONCLUSION: The Malay PSQI was valid and reliable. Abuse was significantly
associated with poor sleep. As sleep is essential for health and is a good
predictor for mortality among older adults, management of abuse victims should
entail sleep assessment. Interventions or treatment modalities which focus on
improving sleep quality among abuse victims should be designed.
PMID- 28686605
TI - Does the implicit models of leadership influence the scanning of other-race faces
in adults?
AB - The current study aims to identify the relationships between implicit leadership
theoretical (ILT) prototypes / anti-prototype and five facial features (i.e.,
nasion, upper nose, lower nose, and upper lip) of a leader from a different race
than respondents. A sample of 81 Asian respondents viewed a 30-second video of a
Caucasian female who in a non-engaging manner talked about her career
achievements. As participants watch the video, their eye movements were recorded
via an eye tracking devise. While previous research has identified that ILT
influences perceptional and attitudinal ratings of leaders, the current study
extends these findings by confirming the impact of ILT on the gaze patterns of
other race participants, who appear to adopt system one type thinking. This study
advances our understanding in how cognitive categories or schemas influence the
physicality of individuals (i.e., eye gaze or movements). Finally, this study
confirms that individual ILT factors have a relationship with the eye movements
of participants and suggests future research directions.
PMID- 28686606
TI - Plant-fed versus chemicals-fed rhizobacteria of Lucerne: Plant-only teabags
culture media not only increase culturability of rhizobacteria but also recover a
previously uncultured Lysobacter sp., Novosphingobium sp. and Pedobacter sp.
AB - In an effort to axenically culture the previously uncultivable populations of the
rhizobacteria of Lucerne (Medicago sativa L.), we propose plant-only teabags
culture media to mimic the nutritional matrix available in the rhizosphere. Here,
we show that culture media prepared from Lucerne powder teabags substantially
increased the cultivability of Lucerne rhizobacteria compared with a standard
nutrient agar, where we found that the cultivable populations significantly
increased by up to 60% of the total bacterial numbers as estimated by
Quantitative Real-time Polymerase Chain Reaction (qRT-PCR). Cluster analysis of
16S rDNA Polymerase Chain Reaction-Denaturing Gradient Gel Electrophoresis (PCR
DGGE) of cultivable Colony-Forming Units (CFUs) revealed a more distinct
composition and separation of bacterial populations recovered on the plant-only
teabags culture media than those developed on a standard nutrient agar. Further,
the new plant medium gave preference to the micro-symbiont Sinorhizobium
meliloti, and succeeded in isolating a number of not-yet-cultured bacteria, most
closely matched to Novosphingobium sp., Lysobacter sp. and Pedobacter sp. The
present study may encourage other researchers to consider moving from the well
established standard culture media to the challenging new plant-only culture
media. Such a move may reveal previously hidden members of rhizobacteria, and
help to further explore their potential environmental impacts.
PMID- 28686608
TI - Biodiversity conservation in an anthropized landscape: Trees, not patch size
drive, bird community composition in a low-input agro-ecosystem.
AB - One of the most typical agro-ecosystems in the Llanos de Ojuelos, a semi-arid
region of central Mexico, is that of fruit-production orchards of nopales
(prickly pear cacti). This perennial habitat with complex vertical structure
provides refuge and food for at least 112 species of birds throughout the year.
Nopal orchards vary in their internal structure, size and shrub/tree composition,
yet these factors have unknown effects on the animals that use them. To further
understand the conservation potential of this agro-ecosystem, we evaluated the
effects of patch-size and the presence of trees on bird community composition, as
well as several habitat variables, through an information-theoretical modelling
approach. Community composition was obtained through a year of census transects
in 12 orchards. The presence of trees in the orchards was the major driver of
bird communities followed by seasonality; bird communities are independent of
patch size, except for small orchard patches that benefit black-chin sparrows,
which are considered a sensitive species. At least 55 species of six trophic
guilds (insectivores, granivores, carnivores, nectivores, omnivores, and
frugivores) used the orchards. Orchards provide adequate habitat and food
resources for several sensitive species of resident and migratory sparrows. The
attributes that make orchards important for birds: trees, shrubs, herb seeds, and
open patches can be managed to maintain native biodiversity in highly anthropized
regions with an urgent need to find convergence between production and biological
conservation.
PMID- 28686607
TI - Cerebellar anodal tDCS increases implicit learning when strategic re-aiming is
suppressed in sensorimotor adaptation.
AB - Neurophysiological and neuroimaging work suggests that the cerebellum is
critically involved in sensorimotor adaptation. Changes in cerebellar function
alter behaviour when compensating for sensorimotor perturbations, as shown by non
invasive stimulation of the cerebellum and studies involving patients with
cerebellar degeneration. It is known, however, that behavioural responses to
sensorimotor perturbations reflect both explicit processes (such as volitional
aiming to one side of a target to counteract a rotation of visual feedback) and
implicit, error-driven updating of sensorimotor maps. The contribution of the
cerebellum to these explicit and implicit processes remains unclear. Here, we
examined the role of the cerebellum in sensorimotor adaptation to a 30 degrees
rotation of visual feedback of hand position during target-reaching, when the
capacity to use explicit processes was manipulated by controlling movement
preparation times. Explicit re-aiming was suppressed in one condition by
requiring subjects to initiate their movements within 300ms of target
presentation, and permitted in another condition by requiring subjects to wait
approximately 1050ms after target presentation before movement initiation.
Similar to previous work, applying anodal transcranial direct current stimulation
(tDCS; 1.5mA) to the right cerebellum during adaptation resulted in faster
compensation for errors imposed by the rotation. After exposure to the rotation,
we evaluated implicit remapping in no-feedback trials after providing
participants with explicit knowledge that the rotation had been removed.
Crucially, movements were more adapted in these no-feedback trials following
cerebellar anodal tDCS than after sham stimulation in both long and short
preparation groups. Thus, cerebellar anodal tDCS increased implicit remapping
during sensorimotor adaptation, irrespective of preparation time constraints. The
results are consistent with the possibility that the cerebellum contributes to
the formation of new visuomotor maps that correct perturbations in sensory
feedback, even when explicit processes are suppressed during sensorimotor
adaptation.
PMID- 28686609
TI - Self-consistent theory of transcriptional control in complex regulatory
architectures.
AB - Individual regulatory proteins are typically charged with the simultaneous
regulation of a battery of different genes. As a result, when one of these
proteins is limiting, competitive effects have a significant impact on the
transcriptional response of the regulated genes. Here we present a general
framework for the analysis of any generic regulatory architecture that accounts
for the competitive effects of the regulatory environment by isolating these
effects into an effective concentration parameter. These predictions are
formulated using the grand-canonical ensemble of statistical mechanics and the
fold-change in gene expression is predicted as a function of the number of
transcription factors, the strength of interactions between the transcription
factors and their DNA binding sites, and the effective concentration of the
transcription factor. The effective concentration is set by the transcription
factor interactions with competing binding sites within the cell and is
determined self-consistently. Using this approach, we analyze regulatory
architectures in the grand-canonical ensemble ranging from simple repression and
simple activation to scenarios that include repression mediated by DNA looping of
distal regulatory sites. It is demonstrated that all the canonical expressions
previously derived in the case of an isolated, non-competing gene, can be
generalised by a simple substitution to their grand canonical counterpart, which
allows for simple intuitive incorporation of the influence of multiple competing
transcription factor binding sites. As an example of the strength of this
approach, we build on these results to present an analytical description of
transcriptional regulation of the lac operon.
PMID- 28686610
TI - Genetic differentiation of spring-spawning and fall-spawning male Atlantic
sturgeon in the James River, Virginia.
AB - Atlantic sturgeon (Acipenser oxyrinchus oxyrinchus, Acipenseridae) populations
are currently at severely depleted levels due to historic overfishing, habitat
loss, and pollution. The importance of biologically correct stock structure for
effective conservation and management efforts is well known. Recent improvements
in our understanding of Atlantic sturgeon migrations, movement, and the
occurrence of putative dual spawning groups leads to questions regarding the true
stock structure of this endangered species. In the James River, VA specifically,
captures of spawning Atlantic sturgeon and accompanying telemetry data suggest
there are two discrete spawning groups of Atlantic sturgeon. The two putative
spawning groups were genetically evaluated using a powerful microsatellite marker
suite to determine if they are genetically distinct. Specifically, this study
evaluates the genetic structure, characterizes the genetic diversity, estimates
effective population size, and measures inbreeding of Atlantic sturgeon in the
James River. The results indicate that fall and spring spawning James River
Atlantic sturgeon groups are genetically distinct (overall FST = 0.048, F'ST =
0.181) with little admixture between the groups. The observed levels of genetic
diversity and effective population sizes along with the lack of detected
inbreeding all indicated that the James River has two genetically healthy
populations of Atlantic sturgeon. The study also demonstrates that samples from
adult Atlantic sturgeon, with proper sample selection criteria, can be
informative when creating reference population databases. The presence of two
genetically-distinct spawning groups of Atlantic sturgeon within the James River
raises concerns about the current genetic assignment used by managers. Other
nearby rivers may also have dual spawning groups that either are not accounted
for or are pooled in reference databases. Our results represent the second
documentation of genetically distinct dual spawning groups of Atlantic sturgeon
in river systems along the U.S. Atlantic coast, suggesting that current reference
population database should be updated to incorporate both new samples and our
increased understanding of Atlantic sturgeon life history.
PMID- 28686611
TI - Yorkie is required to restrict the injury responses in planarians.
AB - Regeneration requires the precise integration of cues that initiate
proliferation, direct differentiation, and ultimately re-pattern tissues to the
proper size and scale. Yet how these processes are integrated with wounding
responses remains relatively unknown. The freshwater planarian, Schmidtea
mediterranea, is an ideal model to study the stereotyped proliferative and
transcriptional responses to injury due to its high capacity for regeneration.
Here, we characterize the effector of the Hippo signalling cascade, yorkie,
during planarian regeneration and its role in restricting early injury responses.
In yki(RNAi) regenerating animals, wound responses are hyper-activated such that
both stem cell proliferation and the transcriptional wound response program are
heighted and prolonged. Using this observation, we also uncovered novel wound
induced genes by RNAseq that were de-repressed in yki(RNAi) animals compared with
controls. Additionally, we show that yki(RNAi) animals have expanded epidermal
and muscle cell populations, which we hypothesize are the increased sources of
wound-induced genes. Finally, we show that in yki(RNAi) animals, the sensing of
the size of an injury by eyes or the pharynx is not appropriate, and the brain,
gut, and midline cannot remodel or scale correctly to the size of the
regenerating fragment. Taken together, our results suggest that yki functions as
a key molecule that can integrate multiple aspects of the injury response
including proliferation, apoptosis, injury-induced transcription, and patterning.
PMID- 28686613
TI - Correction: Tetraspanin 6: A novel regulator of hippocampal synaptic transmission
and long term plasticity.
AB - [This corrects the article DOI: 10.1371/journal.pone.0171968.].
PMID- 28686612
TI - Evaluating phecodes, clinical classification software, and ICD-9-CM codes for
phenome-wide association studies in the electronic health record.
AB - OBJECTIVE: To compare three groupings of Electronic Health Record (EHR) billing
codes for their ability to represent clinically meaningful phenotypes and to
replicate known genetic associations. The three tested coding systems were the
International Classification of Diseases, Ninth Revision, Clinical Modification
(ICD-9-CM) codes, the Agency for Healthcare Research and Quality Clinical
Classification Software for ICD-9-CM (CCS), and manually curated "phecodes"
designed to facilitate phenome-wide association studies (PheWAS) in EHRs. METHODS
AND MATERIALS: We selected 100 disease phenotypes and compared the ability of
each coding system to accurately represent them without performing additional
groupings. The 100 phenotypes included 25 randomly-chosen clinical phenotypes
pursued in prior genome-wide association studies (GWAS) and another 75 common
disease phenotypes mentioned across free-text problem lists from 189,289
individuals. We then evaluated the performance of each coding system to replicate
known associations for 440 SNP-phenotype pairs. RESULTS: Out of the 100 tested
clinical phenotypes, phecodes exactly matched 83, compared to 53 for ICD-9-CM and
32 for CCS. ICD-9-CM codes were typically too detailed (requiring custom
groupings) while CCS codes were often not granular enough. Among 440 tested known
SNP-phenotype associations, use of phecodes replicated 153 SNP-phenotype pairs
compared to 143 for ICD-9-CM and 139 for CCS. Phecodes also generally produced
stronger odds ratios and lower p-values for known associations than ICD-9-CM and
CCS. Finally, evaluation of several SNPs via PheWAS identified novel potential
signals, some seen in only using the phecode approach. Among them, rs7318369 in
PEPD was associated with gastrointestinal hemorrhage. CONCLUSION: Our results
suggest that the phecode groupings better align with clinical diseases mentioned
in clinical practice or for genomic studies. ICD-9-CM, CCS, and phecode groupings
all worked for PheWAS-type studies, though the phecode groupings produced
superior results.
PMID- 28686614
TI - The effects of sampling on the efficiency and accuracy of k-mer indexes:
Theoretical and empirical comparisons using the human genome.
AB - One of the most common ways to search a sequence database for sequences that are
similar to a query sequence is to use a k-mer index such as BLAST. A big problem
with k-mer indexes is the space required to store the lists of all occurrences of
all k-mers in the database. One method for reducing the space needed, and also
query time, is sampling where only some k-mer occurrences are stored. Most
previous work uses hard sampling, in which enough k-mer occurrences are retained
so that all similar sequences are guaranteed to be found. In contrast, we study
soft sampling, which further reduces the number of stored k-mer occurrences at a
cost of decreasing query accuracy. We focus on finding highly similar local
alignments (HSLA) over nucleotide sequences, an operation that is fundamental to
biological applications such as cDNA sequence mapping. For our comparison, we use
the NCBI BLAST tool with the human genome and human ESTs. When identifying HSLAs,
we find that soft sampling significantly reduces both index size and query time
with relatively small losses in query accuracy. For the human genome and HSLAs of
length at least 100 bp, soft sampling reduces index size 4-10 times more than
hard sampling and processes queries 2.3-6.8 times faster, while still achieving
retention rates of at least 96.6%. When we apply soft sampling to the problem of
mapping ESTs against the genome, we map more than 98% of ESTs perfectly while
reducing the index size by a factor of 4 and query time by 23.3%. These results
demonstrate that soft sampling is a simple but effective strategy for performing
efficient searches for HSLAs. We also provide a new model for sampling with BLAST
that predicts empirical retention rates with reasonable accuracy by modeling two
key problem factors.
PMID- 28686615
TI - STAT3 balances myocyte hypertrophy vis-a-vis autophagy in response to Angiotensin
II by modulating the AMPKalpha/mTOR axis.
AB - Signal transducers and activators of transcription 3 (STAT3) is known to
participate in various cardiovascular signal transduction pathways, including
those responsible for cardiac hypertrophy and cytoprotection. However, the role
of STAT3 signaling in cardiomyocyte autophagy remains unclear. We tested the
hypothesis that Angiotensin II (Ang II)-induced cardiomyocyte hypertrophy is
effected, at least in part, through STAT3-mediated inhibition of cellular
autophagy. In H9c2 cells, Ang II treatment resulted in STAT3 activation and
cellular hypertrophy in a dose-dependent manner. Ang II enhanced autophagy,
albeit without impacting AMPKalpha/mTOR signaling or cellular ADP/ATP ratio.
Pharmacologic inhibition of STAT3 with WP1066 suppressed Ang II-induced myocyte
hypertrophy and mRNA expression of hypertrophy-related genes ANP and beta-MHC.
These molecular events were recapitulated in cells with STAT3 knockdown. Genetic
or pharmacologic inhibition of STAT3 significantly increased myocyte ADP/ATP
ratio and enhanced autophagy through AMPKalpha/mTOR signaling. Pharmacologic
activation and inhibition of AMPKalpha attenuated and exaggerated, respectively,
the effects of Ang II on ANP and beta-MHC gene expression, while concomitant
inhibition of STAT3 accentuated the inhibition of hypertrophy. Together, these
data indicate that novel nongenomic effects of STAT3 influence myocyte energy
status and modulate AMPKalpha/mTOR signaling and autophagy to balance the
transcriptional hypertrophic response to Ang II stimulation. These findings may
have significant relevance for various cardiovascular pathological processes
mediated by Ang II signaling.
PMID- 28686616
TI - Diagnostic accuracy of tablet-based software for the detection of concussion.
AB - Despite the high prevalence of traumatic brain injuries (TBI), there are few
rapid and straightforward tests to improve its assessment. To this end, we
developed a tablet-based software battery ("BrainCheck") for concussion detection
that is well suited to sports, emergency department, and clinical settings. This
article is a study of the diagnostic accuracy of BrainCheck. We administered
BrainCheck to 30 TBI patients and 30 pain-matched controls at a hospital
Emergency Department (ED), and 538 healthy individuals at 10 control test sites.
We compared the results of the tablet-based assessment against physician
diagnoses derived from brain scans, clinical examination, and the SCAT3 test, a
traditional measure of TBI. We found consistent distributions of normative data
and high test-retest reliability. Based on these assessments, we defined a
composite score that distinguishes TBI from non-TBI individuals with high
sensitivity (83%) and specificity (87%). We conclude that our testing application
provides a rapid, portable testing method for TBI.
PMID- 28686618
TI - Network effects in environmental justice struggles: An investigation of conflicts
between mining companies and civil society organizations from a network
perspective.
AB - This paper examines conflicts that occur between mining companies and civil
society organizations (CSOs) around the world and offers an innovative analysis
of mining conflicts from a social network perspective. The analysis showed that,
as the number of CSOs involved in a conflict increased, its outcome was more
likely to be perceived as a success in terms of environmental justice (EJ); if a
CSO was connected to other central CSOs, the average perception of EJ success was
likely to increase; and as network distance between two conflicts increased (or
decreased), they were more likely to lead to different (or similar) EJ outcomes.
Such network effects in mining conflicts have policy implications for EJ
movements. It would be a strategic move on the part of successful CSOs to become
involved in other major conflicts and disseminate information about how they
achieved greater EJ success.
PMID- 28686617
TI - Dengue virus specific IgY provides protection following lethal dengue virus
challenge and is neutralizing in the absence of inducing antibody dependent
enhancement.
AB - Dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) are severe disease
manifestations that can occur following sequential infection with different
dengue virus serotypes (DENV1-4). At present, there are no licensed therapies to
treat DENV-induced disease. DHF and DSS are thought to be mediated by serotype
cross-reactive antibodies that facilitate antibody-dependent enhancement (ADE) by
binding to viral antigens and then Fcgamma receptors (FcgammaR) on target myeloid
cells. Using genetically engineered DENV-specific antibodies, it has been shown
that the interaction between the Fc portion of serotype cross-reactive antibodies
and FcgammaR is required to induce ADE. Additionally, it was demonstrated that
these antibodies were as neutralizing as their non-modified variants, were
incapable of inducing ADE, and were therapeutic following a lethal, antibody
enhanced infection. Therefore, we hypothesized that avian IgY, which do not
interact with mammalian FcgammaR, would provide a novel therapy for DENV-induced
disease. We demonstrate here that goose-derived anti-DENV2 IgY neutralized DENV2
and did not induce ADE in vitro. Anti-DENV2 IgY was also protective in vivo when
administered 24 hours following a lethal DENV2 infection. We were also able to
demonstrate via epitope mapping that both full-length and alternatively spliced
anti-DENV2 IgY recognized different epitopes, including epitopes that have not
been previously identified. These observations provide evidence for the potential
therapeutic applications of goose-derived anti-DENV2 IgY.
PMID- 28686619
TI - Rare variants of small effect size in neuronal excitability genes influence
clinical outcome in Japanese cases of SCN1A truncation-positive Dravet syndrome.
AB - Dravet syndrome (DS) is a rare, devastating form of childhood epilepsy that is
often associated with mutations in the voltage-gated sodium channel gene, SCN1A.
There is considerable variability in expressivity within families, as well as
among individuals carrying the same primary mutation, suggesting that clinical
outcome is modulated by variants at other genes. To identify modifier gene
variants that contribute to clinical outcome, we sequenced the exomes of 22
individuals at both ends of a phenotype distribution (i.e., mild and severe
cognitive condition). We controlled for variation associated with different
mutation types by limiting inclusion to individuals with a de novo truncation
mutation resulting in SCN1A haploinsufficiency. We performed tests aimed at
identifying 1) single common variants that are enriched in either phenotypic
group, 2) sets of common or rare variants aggregated in and around genes
associated with clinical outcome, and 3) rare variants in 237 candidate genes
associated with neuronal excitability. While our power to identify enrichment of
a common variant in either phenotypic group is limited as a result of the rarity
of mild phenotypes in individuals with SCN1A truncation variants, our top
candidates did not map to functional regions of genes, or in genes that are known
to be associated with neurological pathways. In contrast, we found a
statistically-significant excess of rare variants predicted to be damaging and of
small effect size in genes associated with neuronal excitability in severely
affected individuals. A KCNQ2 variant previously associated with benign neonatal
seizures is present in 3 of 12 individuals in the severe category. To compare our
results with the healthy population, we performed a similar analysis on whole
exome sequencing data from 70 Japanese individuals in the 1000 genomes project.
Interestingly, the frequency of rare damaging variants in the same set of
neuronal excitability genes in healthy individuals is nearly as high as in
severely affected individuals. Rather than a single common gene/variant modifying
clinical outcome in SCN1A-related epilepsies, our results point to the cumulative
effect of rare variants with little to no measurable phenotypic effect (i.e.,
typical genetic background) unless present in combination with a disease-causing
truncation mutation in SCN1A.
PMID- 28686620
TI - Structural transitions during large ribosomal subunit maturation analyzed by
tethered nuclease structure probing in S. cerevisiae.
AB - Yeast large ribosomal subunit (LSU) precursors are subject to substantial changes
in protein composition during their maturation due to coordinated transient
interactions with a large number of ribosome biogenesis factors and due to the
assembly of ribosomal proteins. These compositional changes go along with
stepwise processing of LSU rRNA precursors and with specific rRNA folding events,
as revealed by recent cryo-electron microscopy analyses of late nuclear and
cytoplasmic LSU precursors. Here we aimed to analyze changes in the spatial rRNA
surrounding of selected ribosomal proteins during yeast LSU maturation. For this
we combined a recently developed tethered tertiary structure probing approach
with both targeted and high throughput readout strategies. Several structural
features of late LSU precursors were faithfully detected by this procedure. In
addition, the obtained data let us suggest that early rRNA precursor processing
events are accompanied by a global transition from a flexible to a spatially
restricted rRNA conformation. For intermediate LSU precursors a number of
structural hallmarks could be addressed which include the fold of the internal
transcribed spacer between 5.8S rRNA and 25S rRNA, the orientation of the central
protuberance and the spatial organization of the interface between LSU rRNA
domains I and III.
PMID- 28686621
TI - Risk of bias and confounding of observational studies of Zika virus infection: A
scoping review of research protocols.
AB - INTRODUCTION: Given the severity and impact of the current Zika virus (ZIKV)
outbreak in the Americas, numerous countries have rushed to develop research
studies to assess ZIKV and its potential health consequences. In an effort to
ensure that studies are comprehensive, both internally and externally valid, and
with reliable results, the World Health Organization, the Pan American Health
Organization, Institut Pasteur, the networks of Fiocruz, the Consortia for the
Standardization of Influenza Seroepidemiology (CONSISE) and the International
Severe Acute Respiratory and Emerging Infection Consortium (ISARIC) have
generated six standardized clinical and epidemiological research protocols and
questionnaires to address key public health questions on ZIKV. METHODS: We
conducted a systematic search of ongoing study protocols related to ZIKV
research. We analyzed the content of protocols of 32 cohort studies and 13 case
control studies for systematic bias that could produce erroneous results.
Additionally we aimed to characterize the risks of bias and confounding in
observational studies related to ZIKV and to propose ways to minimize them,
including the use of six newly standardized research protocols. RESULTS:
Observational studies of ZIKV face an array of challenges, including measurement
of exposure and outcomes (microcephaly and Guillain-Barre Syndrome). Potential
confounders need to be measured where known and controlled for in the analysis.
Selection bias due to non-random selection is a significant issue, particularly
in the case-control design, and losses to follow-up is equally important for the
cohort design. CONCLUSION: Observational research seeking to answer key questions
on the ZIKV should consider these restrictions and take precautions to minimize
bias in an effort to provide reliable and valid results. Utilization of the
standardized research protocols developed by the WHO, PAHO, Institut Pasteur, and
CONSISE will harmonize the key methodological aspects of each study design to
minimize bias at different stages of the study. Biases need to be considered by
researchers implementing the standardized protocols as well as by users of
observational epidemiological studies of ZIKV.
PMID- 28686622
TI - Succession of biofilm communities responsible for biofouling of membrane bio
reactors (MBRs).
AB - Biofilm formation is one of the main factors associated with membrane biofouling
in membrane bioreactors (MBRs). As such, it is important to identify the
responsible organisms to develop targeted strategies to control biofouling. This
study investigated the composition and changes in the microbial communities
fouling MBR membranes over time and correlated those changes with an increase in
transmembrane pressure (TMP). Based on qPCR data, bacteria were the dominant taxa
of the biofilm (92.9-98.4%) relative to fungi (1.5-6.9%) and archaea (0.03
0.07%). NMDS analysis indicated that during the initial stages of operation, the
biofilm communities were indistinguishable from those found in the sludge.
However, the biofilm community significantly diverged from the sludge over time
and ultimately showed a unique biofilm profile. This suggested that there was
strong selection for a group of organisms that were biofilm specialists. This
pattern of succession and selection was correlated with the rapid increase in
TMP, where bacteria including Rhodospirillales, Sphingomonadales and Rhizobiales
dominated the biofilm at this time. While most of the identified fungal OTUs
matched Candida sp., the majority of fungal communities were unclassified by 18S
rRNA gene sequencing. Collectively, the data suggests that bacteria, primarily,
along with fungi may play an important role in the rapid TMP increase and loss of
system performance.
PMID- 28686623
TI - Xist RNA repeat E is essential for ASH2L recruitment to the inactive X and
regulates histone modifications and escape gene expression.
AB - Long non-coding RNA Xist plays a crucial role in establishing and maintaining X
chromosome inactivation (XCI) which is a paradigm of long non-coding RNA-mediated
gene regulation. Xist has Xist-specific repeat elements A-F which are conserved
among eutherian mammals, underscoring their functional importance. Here we report
that Xist RNA repeat E, a conserved Xist repeat element in the Xist exon 7,
interacts with ASH2L and contributes to maintenance of escape gene expression
level on the inactive X-chromosome (Xi) during XCI. The Xist repeat E-deletion
mutant female ES cells show the depletion of ASH2L from the Xi upon
differentiation. Furthermore, a subset of escape genes exhibits unexpectedly
higher expression in the repeat E mutant cells than the cells expressing wildtype
Xist during X-inactivation, whereas the silencing of X-linked non-escape genes is
not affected. We discuss the implications of these results to understand the role
of ASH2L and Xist repeat E for histone modifications and escape gene regulation
during random X-chromosome inactivation.
PMID- 28686624
TI - Adverse effects of chronic exposure to nonylphenol on non-alcoholic fatty liver
disease in male rats.
AB - Endocrine-disrupting chemical (EDC) has been thought to play a role in non
alcoholic fatty liver disease (NAFLD). However, the toxic effects of Nonylphenol
(NP), an EDC, on non-alcoholic fatty liver disease have never been elaborated.
This study aimed to investigate whether exposure to NP could induce NAFDL, a
promoting effect of high-sucrose-high-fat diet (HSHFD) on the adverse effects
caused by NP was evaluated. Fourth eight male rats were assigned to four groups
and each group was treated with a specific testing sample: normal-diet (ND)
control group (C-ND); normal diet plus NP (180mg/kg/day) group (NP-ND); high
sucrose-high-fat-diet control group (C-HSHFD); HSHFD plus NP (180mg/kg/day) group
(NP-HSHFD). At the age of 80 day, sonogram presents diffusely increased hepatic
echogenicity in the NP-HSHFD group. The oblique diameter of liver in the NP-HSHFD
group was significantly bigger than that in both the C-ND and NP-ND groups. At
the age of 90 day, exposure to NP-HSHFD and NP-ND caused a significant increase
in NP concentration in liver as compared to the C-ND group. The rats in the
groups treated with NP+ND, HSHFD and NP+HSHFD produced significant increases in
the body weight, fat weight and FMI, respectively, when compared to the C-ND
group. The liver weight and hepatosomatic indexes (HIS) of rats in the NP-HSHFD
group are higher than those in the C-HSHFD group. Exposure to NP-HSHFD induced
the increases in plasma alanine aminotransferase (ALT), aspartate
aminotransferase (AST), cholesterol (TC), triglyceride (TG) and low density
lipoprotein (LDL) as compared to the C-ND group. Morphological examination of
liver tissue from rats exposed to NP+HSHFD shown steatosis with marked
accumulation of lipid droplets, hepatocellular ballooning degeneration and
inflammatory cell infiltration. Chronic exposure to NP might induce NAFLD in male
rats. The high-sucrose-high-fat diet accelerates and exacerbates the development
of NAFLD caused by NP exposure.
PMID- 28686625
TI - Genotyping assay for differentiation of wild-type and vaccine viruses in subjects
immunized with live attenuated influenza vaccine.
AB - Live attenuated influenza vaccines (LAIVs) are considered as safe and effective
tool to control influenza in different age groups, especially in young children.
An important part of the LAIV safety evaluation is the detection of vaccine virus
replication in the nasopharynx of the vaccinees, with special attention to a
potential virus transmission to the unvaccinated close contacts. Conducting LAIV
clinical trials in some geographical regions with year-round circulation of
influenza viruses warrants the development of robust and reliable tools for
differentiating vaccine viruses from wild-type influenza viruses in nasal
pharyngeal wash (NPW) specimens of vaccinated subjects. Here we report the
development of genotyping assay for the detection of wild-type and vaccine-type
influenza virus genes in NPW specimens of young children immunized with Russian
backbone seasonal trivalent LAIV using Sanger sequencing from newly designed
universal primers. The new primer set allowed amplification and sequencing of
short fragments of viral genes in NPW specimens and appeared to be more sensitive
than conventional real-time RT-PCR protocols routinely used for the detection and
typing/subtyping of influenza virus in humans. Furthermore, the new assay is
capable of defining the origin of wild-type influenza virus through BLAST search
with the generated sequences of viral genes fragments.
PMID- 28686626
TI - BIG LEAF is a regulator of organ size and adventitious root formation in poplar.
AB - Here we report the discovery through activation tagging and subsequent
characterization of the BIG LEAF (BL) gene from poplar. In poplar, BL regulates
leaf size via positively affecting cell proliferation. Up and downregulation of
the gene led to increased and decreased leaf size, respectively, and these
phenotypes corresponded to increased and decreased cell numbers. BL function
encompasses the early stages of leaf development as native BL expression was
specific to the shoot apical meristem and leaf primordia and was absent from the
later stages of leaf development and other organs. Consistently, BL
downregulation reduced leaf size at the earliest stages of leaf development.
Ectopic expression in mature leaves resulted in continued growth most probably
via sustained cell proliferation and thus the increased leaf size. In contrast to
the positive effect on leaf growth, ectopic BL expression in stems interfered
with and significantly reduced stem thickening, suggesting that BL is a highly
specific activator of growth. In addition, stem cuttings from BL overexpressing
plants developed roots, whereas the wild type was difficult to root,
demonstrating that BL is a positive regulator of adventitious rooting. Large
transcriptomic changes in plants that overexpressed BL indicated that BL may have
a broad integrative role, encompassing many genes linked to organ growth. We
conclude that BL plays a fundamental role in control of leaf size and thus may be
a useful tool for modifying plant biomass productivity and adventitious rooting.
PMID- 28686627
TI - WGA-based lectin affinity gel electrophoresis: A novel method for the detection
of O-GlcNAc-modified proteins.
AB - Post-translational modification with O-linked beta-N-acetylglucosamine (O-GlcNAc)
occurs selectively on serine and/or threonine residues of cytoplasmic and nuclear
proteins, and dynamically regulates their molecular functions. Since conventional
strategies to evaluate the O-GlcNAcylation level of a specific protein require
time-consuming steps, the development of a rapid and easy method for the
detection and quantification of an O-GlcNAcylated protein has been a challenging
issue. Here, we describe a novel method in which O-GlcNAcylated and non-O
GlcNAcylated forms of proteins are separated by lectin affinity gel
electrophoresis using wheat germ agglutinin (WGA), which primarily binds to N
acetylglucosamine residues. Electrophoresis of cell lysates through a gel
containing copolymerized WGA selectively induced retardation of the mobility of O
GlcNAcylated proteins, thereby allowing the simultaneous visualization of both
the O-GlcNAcylated and the unmodified forms of proteins. This method is therefore
useful for the quantitative detection of O-GlcNAcylated proteins.
PMID- 28686628
TI - The rural pipeline to longer-term rural practice: General practitioners and
specialists.
AB - BACKGROUND: Rural medical workforce shortage contributes to health disadvantage
experienced by rural communities worldwide. This study aimed to determine the
regional results of an Australian Government sponsored national program to
enhance the Australian rural medical workforce by recruiting rural background
students and establishing rural clinical schools (RCS). In particular, we wished
to determine predictors of graduates' longer-term rural practice and whether the
predictors differ between general practitioners (GPs) and specialists. METHODS: A
cross-sectional cohort study, conducted in 2012, of 729 medical graduates of The
University of Queensland 2002-2011. The outcome of interest was primary place of
graduates' practice categorised as rural for at least 50% of time since
graduation ('Longer-term Rural Practice', LTRP) among GPs and medical
specialists. The main exposures were rural background (RB) or metropolitan
background (MB), and attendance at a metropolitan clinical school (MCS) or the
Rural Clinical School for one year (RCS-1) or two years (RCS-2). RESULTS:
Independent predictors of LTRP (odds ratio [95% confidence interval]) were RB
(2.10 [1.37-3.20]), RCS-1 (2.85 [1.77-4.58]), RCS-2 (5.38 [3.15-9.20]), GP (3.40
[2.13-5.43]), and bonded scholarship (2.11 [1.19-3.76]). Compared to being
single, having a metropolitan background partner was a negative predictor (0.34
[0.21-0.57]). The effects of RB and RCS were additive-compared to MB and MCS
(Reference group): RB and RCS-1 (6.58[3.32-13.04]), RB and RCS-2 (10.36[4.89
21.93]). Although specialists were less likely than GPs to be in LTRP, the
pattern of the effects of rural exposures was similar, although some significant
differences in the effects of the duration of RCS attendance, bonded scholarships
and partner's background were apparent. CONCLUSIONS: Among both specialists and
GPs, rural background and rural clinical school attendance are independent,
duration-dependent, and additive, predictors of longer-term rural practice.
Metropolitan-based medical schools can enhance both specialist and GP rural
medical workforce by enrolling rural background medical students and providing
them with long-term rural undergraduate clinical training. Policy settings to
achieve optimum rural workforce outcomes may differ between specialists and GPs.
PMID- 28686629
TI - The characteristics of screening and confirmatory test results for HIV in Xi'an,
China.
AB - OBJECTIVES: Individuals with recent or acute HIV infection are more infectious
than those with established infection. Our objective was to analyze the
characteristics of detection among HIV infections in Xi'an. METHODS: A 4th
generation kit (Architect HIV Ag/Ab Combo) and three 3rd-generationEIA kits
(WanTai, XinChuang and Livzon) were used for HIV screening. Overall, 665
individuals were identified as positive and were tested by western blotting (WB).
The characteristics of the screening and confirmatory tests were analyzed,
including the band patterns, the early detection performance and the false
positive rates. RESULTS: In total, 561 of the 665 patients were confirmed as
having HIV-1 infection, and no HIV-2 specific band was observed. Among these 561
WB-positive cases, reactivity to greater than or equal to 9 antigens was the most
commonly observed pattern (83.18%), and the absence of reactivity to p17, p31 and
gp41 was detected in 6.44%, 5.9% and 2.86% of the cases, respectively. Two cases
were positive by the 4th-generation assay but negative by the 3rd-generation
assay for HIV screening and had seroconversion. The false-positive rate of the
Architect HIV Ag/Ab Combo (22.01%) was significantly higher than those of WanTai
(9.88%), XinChuang (10.87%) and Livzon (8.93%), p<0.05. CONCLUSION: HIV infection
in Xi'an is mainly caused by HIV-1, and individuals are rarely identified at the
early phase. Although the false-positive rate of the 4th-generation assay was
higher than that of the 3rd-generation assay, it is still recommended for use as
the initial HIV screening test for high-risk individuals. In Xi'an, a 3rd
generation assay for screening could be considered.
PMID- 28686630
TI - Caspase-6 mediates resistance against Burkholderia pseudomallei infection and
influences the expression of detrimental cytokines.
AB - Caspase-6 is a member of the executioner caspases and known to play a role in
innate and adaptive immune processes. However, its role in infectious diseases
has rarely been addressed yet. We here examined the impact of caspase-6 in an in
vivo infection model using the Gram-negative rod Burkholderia pseudomallei,
causing the infectious disease melioidosis that is endemic in tropical and
subtropical areas around the world. Caspase-6-/- and C57BL/6 wild type mice were
challenged with B. pseudomallei for comparing mortality, bacterial burden and
inflammatory cytokine expression. Bone-marrow derived macrophages were used to
analyse the bactericidal activity in absence of caspase-6. Caspase-6 deficiency
was associated with higher mortality and bacterial burden in vivo after B.
pseudomallei infection. The bactericidal activity of caspase-6-/- macrophages was
impaired compared to wild type cells. Caspase-6-/- mice showed higher expression
of the IL-1beta gene, known to be detrimental in murine melioidosis. Expression
of the IL-10 gene was also increased in caspase-6-/- mice as early as 6 hours
after infection. Treatment with exogenous IL-10 rendered mice more susceptible
against B. pseudomallei challenge. Thus, caspase-6 seems to play a crucial role
for determining resistance against the causative agent of melioidosis. To our
knowledge this is the first report showing that caspase-6 is crucial for
mediating resistance in an in vivo infection model. Caspase-6 influences the
expression of detrimental cytokines and therefore seems to be important for
achieving a well-balanced immune response that contributes for an efficient
elimination of the pathogen.
PMID- 28686631
TI - A new approach for the analysis of facial growth and age estimation: Iris ratio.
AB - The study of facial growth is explored in many fields of science, including
anatomy, genetics, and forensics. In the field of forensics, it acts as a
valuable tool for combating child pornography. The present research proposes a
new method, based on relative measurements and fixed references of the human face
specifically considering measurements of the diameter of the iris (iris ratio)
for the analysis of facial growth in association with age in children and sub
adults. The experimental sample consisted of digital photographs of 1000
Brazilian subjects, aged between 6 and 22 years, distributed equally by sex and
divided into five specific age groups (6, 10, 14, 18, and 22 year olds +/- one
month). The software package SAFF-2D(r) (Forensic Facial Analysis System,
Brazilian Federal Police, Brazil) was used for positioning 11 landmarks on the
images. Ten measurements were calculated and used as fixed references to evaluate
the growth of the other measurements for each age group, as well the accumulated
growth (6-22 years old). The Intraclass Correlation Coefficient (ICC) was applied
for the evaluation of intra-examiner and inter-examiner reliability within a
specific set of images. Pearson's Correlation Coefficient was used to assess the
association between each measurement taken and the respective age groups. ANOVA
and Post-hoc Tukey tests were used to search for statistical differences between
the age groups. The outcomes indicated that facial structures grow with different
timing in children and adolescents. Moreover, the growth allometry expressed in
this study may be used to understand what structures have more or less
proportional variation in function for the age ranges studied. The diameter of
the iris was found to be the most stable measurement compared to the others and
represented the best cephalometric measurement as a fixed reference for facial
growth ratios (or indices). The method described shows promising potential for
forensic applications, especially as part of the armamentarium against crimes
involving child pornography and child abuse.
PMID- 28686632
TI - Autophagy-dependent regulation of tumor metastasis by myeloid cells.
AB - Autophagy is a vital process controlling the lysosomal degradation of cellular
organelles and thereby regulating tissue homeostasis in an environment-dependent
fashion. Recent studies have unveiled the critical role of tumor cell-derived
autophagy in regulating pro-tumor and anti-tumor processes depending on different
stages and tumor microenvironments. However, the precise mechanism whereby
autophagy regulates tumor progression remains largely unclear. Since myeloid
cells contribute to tumor progression and metastasis, we evaluated the role of
myeloid cell-specific autophagy in the regulation of tumor progression. We found
that the number and size of metastatic lesions were smaller in myeloid cell
specific autophagy-deficient mice. Furthermore, autophagy-mediated regulation of
TGF-beta in myeloid cells was associated with the induction of epithelial
mesenchymal transition (EMT), which increases the invasive and metastatic
potentials of tumor cells. Myeloid-derived autophagy also plays a critical role
in impairing antitumor immune responses and promoting the survival and
accumulation of M2 macrophages in tumor tissues in a CSF-1 and TGF-beta-dependent
manner. Taken together, our findings elucidate previously unrecognized mechanisms
by which myeloid cells promote tumor progression through autophagy-mediated
regulation of malignancy and immune tolerance.
PMID- 28686633
TI - Increased risk for development of coronary artery calcification in subjects with
non-alcoholic fatty liver disease and systemic inflammation.
AB - BACKGROUND: Recent studies have suggested the importance of non-alcoholic fatty
liver disease (NAFLD) and systemic inflammation in the development of
atherosclerosis. The aim of this study was to compare the risk for coronary
artery calcification (CAC) development according to the status of NAFLD and
inflammation over four years of follow-up in subjects without baseline CAC.
METHODS: A total of 1,575 participants in a health screening program were divided
into four groups according to baseline NAFLD state and high-sensitivity C
reactive protein (hs-CRP) (median 0.06 mg/L) levels as follows: no NAFLD and hs
CRP <0.06 mg/L, no NAFLD and hs-CRP >=0.06 mg/L, NAFLD and hs-CRP <0.06 mg/L, and
NAFLD and hs-CRP >=0.06 mg/L. Coronary artery calcium score (CACS) was repeatedly
measured by multi-detector computed tomography at four-year intervals and CAC
development during those intervals was monitored in subjects with baseline CACS =
0. RESULTS: Over four years, 148 subjects (9.4%) developed CAC. The proportion of
subjects who developed CAC was significantly higher in subjects with NAFLD at
baseline compared with those without NAFLD at baseline (6.8 vs. 12.4%, p<0.01),
and it was also higher in subjects with hs-CRP >=0.06 mg/L compared with those
with hs-CRP <0.06 mg/L (7.2 vs. 11.5%, p<0.01). In addition, the proportion of
subjects who developed CAC was highest in subjects with NAFLD and hs-CRP >=0.06
mg/dL, followed by subjects with NAFLD, subjects without NAFLD and hs-CRP >=0.06
mg/L, and subjects without NALFD and hs-CRP <0.05 mg/L at baseline, in that order
(13.7, 10.0, 8.3, and 5.8%, respectively; p for trend<0.01). The odds ratio for
CAC development was highest in subjects with NAFLD and hs-CRP >=0.06 mg/L (1.67,
95% CI 1.01-2.77), though it was attenuated after adjustment for body mass index.
CONCLUSIONS: The concomitant presence of NAFLD and systemic inflammation as
assessed by hs-CRP increases the risk of CAC development over four years.
PMID- 28686634
TI - Similarity measure and domain adaptation in multiple mixture model clustering: An
application to image processing.
AB - This paper considers three crucial issues in processing scaled down image, the
representation of partial image, similarity measure and domain adaptation. Two
Gaussian mixture model based algorithms are proposed to effectively preserve
image details and avoids image degradation. Multiple partial images are clustered
separately through Gaussian mixture model clustering with a scan and select
procedure to enhance the inclusion of small image details. The local image
features, represented by maximum likelihood estimates of the mixture components,
are classified by using the modified Bayes factor (MBF) as a similarity measure.
The detection of novel local features from MBF will suggest domain adaptation,
which is changing the number of components of the Gaussian mixture model. The
performance of the proposed algorithms are evaluated with simulated data and real
images and it is shown to perform much better than existing Gaussian mixture
model based algorithms in reproducing images with higher structural similarity
index.
PMID- 28686635
TI - Visuo-spatial cueing in children with differential reading and spelling profiles.
AB - Dyslexia has been claimed to be causally related to deficits in visuo-spatial
attention. In particular, inefficient shifting of visual attention during spatial
cueing paradigms is assumed to be associated with problems in graphemic parsing
during sublexical reading. The current study investigated visuo-spatial attention
performance in an exogenous cueing paradigm in a large sample (N = 191) of third
and fourth graders with different reading and spelling profiles (controls,
isolated reading deficit, isolated spelling deficit, combined deficit in reading
and spelling). Once individual variability in reaction times was taken into
account by means of z-transformation, a cueing deficit (i.e. no significant
difference between valid and invalid trials) was found for children with combined
deficits in reading and spelling. However, poor readers without spelling problems
showed a cueing effect comparable to controls, but exhibited a particularly
strong right-over-left advantage (position effect). Isolated poor spellers showed
a significant cueing effect, but no position effect. While we replicated earlier
findings of a reduced cueing effect among poor nonword readers (indicating
deficits in sublexical processing), we also found a reduced cueing effect among
children with particularly poor orthographic spelling (indicating deficits in
lexical processing). Thus, earlier claims of a specific association with nonword
reading could not be confirmed. Controlling for ADHD-symptoms reported in a
parental questionnaire did not impact on the statistical analysis, indicating
that cueing deficits are not caused by more general attentional limitations.
Between 31 and 48% of participants in the three reading and/or spelling deficit
groups as well as 32% of the control group showed reduced spatial cueing. These
findings indicate a significant, but moderate association between certain aspects
of visuo-spatial attention and subcomponents of written language processing, the
causal status of which is yet unclear.
PMID- 28686636
TI - Characteristics and outcomes of older HIV-infected patients receiving
antiretroviral therapy in Malawi: A retrospective observation cohort study.
AB - OBJECTIVE: To estimate patients enrolling on antiretroviral therapy (ART) over
time; describe trends in baseline characteristics; and compare immunological
response, loss to follow-up (LTFU), and mortality by three age groups (25-39, 40
49 and >=50 years). DESIGN: A retrospective observation cohort study. METHODS:
This study used routine ART data from two public clinics in Lilongwe, Malawi. All
HIV-infected individuals, except pregnant or breastfeeding women, aged >= 25
years at ART initiation between 2006 and 2015 were included. Poisson regression
models estimated risk of mortality, stratified by age groups. RESULTS: Of 37,378
ART patients, 3,406 were >= 50 years old. Patients aged >= 50 years initiated ART
with more advanced WHO clinical stage and lower CD4 cell count than their younger
counterparts. Older patients had a significantly slower immunological response to
ART in the first 18 months on ART compared to patients aged 25-39 years (p =
0.04). Overall mortality rates were 2.3 (95% confidence Interval (CI) 2.2-2.4),
2.9 (95% CI 2.7-3.2) and 4.6 (95% CI 4.2-5.1) per 100 person-years in patients
aged 25-39 years, 40-49 years and 50 years and older, respectively. Overall LTFU
rates were 6.3 (95% CI 6.1-6.5), 4.5 (95% CI 4.2-4.7), and 5.6 (95% CI 5.1-6.1)
per 100 person years among increasing age cohorts. The proportion of patients
aged >= 50 years and newly enrolling into ART care remained stable at 9% while
the proportion of active ART patients aged >=50 years increased from 10% in 2006
to 15% in 2015. CONCLUSION: Older people had slower immunological response and
higher mortality. Malawi appears to be undergoing a demographic shift in people
living with HIV. Increased consideration of long-term ART-related problems, drug
drug interactions and age-related non-communicable diseases is warranted.
PMID- 28686637
TI - Endotypes of difficult-to-control asthma in inner-city African American children.
AB - African Americans have higher rates of asthma prevalence, morbidity, and
mortality in comparison with other racial groups. We sought to characterize
endotypes of childhood asthma severity in African American patients in an inner
city pediatric asthma population. Baseline blood neutrophils, blood eosinophils,
and 38 serum cytokine levels were measured in a sample of 235 asthmatic children
(6-17 years) enrolled in the NIAID (National Institute of Allergy and Infectious
Diseases)-sponsored Asthma Phenotypes in the Inner City (APIC) study (ICAC (Inner
City Asthma Consortium)-19). Cytokines were quantified using a MILLIPLEX panel
and analyzed on a Luminex analyzer. Patients were classified as Easy-to-Control
or Difficult-to-Control based on the required dose of controller medications over
one year of prospective management. A multivariate variable selection procedure
was used to select cytokines associated with Difficult-to-Control versus Easy-to
Control asthma, adjusting for age, sex, blood eosinophils, and blood neutrophils.
In inner-city African American children, 12 cytokines were significant predictors
of Difficult-to-Control asthma (n = 235). CXCL-1, IL-5, IL-8, and IL-17A were
positively associated with Difficult-to-Control asthma, while IL-4 and IL-13 were
positively associated with Easy-to-Control asthma. Using likelihood ratio
testing, it was observed that in addition to blood eosinophils and neutrophils,
serum cytokines improved the fit of the model. In an inner-city pediatric
population, serum cytokines significantly contributed to the definition of
Difficult-to-Control asthma endotypes in African American children. Mixed
responses characterized by TH2 (IL-5) and TH17-associated cytokines were
associated with Difficult-to-Control asthma. Collectively, these data may
contribute to risk stratification of Difficult-to-Control asthma in the African
American population.
PMID- 28686638
TI - Which immunotherapy product is better for patients allergic to Polistes venom? A
laboratory and clinical study.
AB - BACKGROUND: Venom immunotherapy (VIT) is highly effective in preventing allergic
reactions to insect stings, but the appropriate venom must be used to achieve
clinical protection. In patients with multiple positive results to venoms,
molecular allergy diagnostics or CAP-inhibition may identify the causative venom.
Concerning allergy to venom from Polistes spp. it has been proposed that only the
European species P. dominulus should be used for VIT. However, this
recommendation is not present in any international guideline. Using both
laboratory and clinical data, we aimed to evaluate the reliability of this
proposal. METHODS: We performed an in vitro study using CAP-inhibition to
determine sensitization of 19 patients allergic to Polistes venom. The clinical
study included 191 patients with positive tests to Polistes treated with VIT, 102
were treated with P. dominulus and 89 were treated with a mix of American
Polistes (mAP). RESULTS: The difference in % of inhibition was significant
concerning inhibition of P. dominulus sIgE by P. dominulus venom (79.8%) compared
with inhibition by mAP venom (64.2%) and not significant concerning the
inhibition of mAP sIgE by P. dominulus venom (80.1%) and by mAP venom (73.6%).
Instead, the clinical protection from stings was not statistically different
between the two kinds of venom. CONCLUSION: The data from CAP inhibition would
suggest that the choice of either P. dominulus venom or mAP venom for VIT is
appropriate in patients with CAP inhibition higher than 70%, but the clinical
data show the same odds of protection from stings using for VIT P. dominulus or
mAP venom.
PMID- 28686639
TI - Pain and pain mechanisms in patients with inflammatory arthritis: A Danish
nationwide cross-sectional DANBIO registry survey.
AB - BACKGROUND: Central pain mechanisms may be prominent in subsets of patients with
rheumatoid arthritis (RA), psoriatic arthritis (PsA) and other spondyloarthritis
(SpA). The painDETECT questionnaire (PDQ) identifies neuropathic pain features,
which may act as a proxy for centrally mediated pain. The objectives were to
quantify and characterize pain phenotypes (non-neuropathic vs. neuropathic
features) among Danish arthritis patients using the PDQ, and to assess the
association with on-going inflammation. METHODS: The PDQ was included onto the
DANBIO touch screens at 22 departments of Rheumatology in Denmark for six months.
Clinical data and patient reported outcomes were obtained from DANBIO. A PDQ
score >18 indicated neuropathic pain features, 13-18 unclear pain mechanism and
<13 non-neuropathic pain. RESULTS: Pain data (visual analogue scale, VAS) was
available for 15,978 patients. 7,054 patients completed the PDQ (RA: 3,826, PsA:
1,180, SpA: 1,093). 52% of all patients and 63% of PDQ-completers had VAS pain
score >= 30 mm. The distribution of the PDQ classification-groups (<13/ 13-18/
>18) were; RA: 56%/24%/20%. PsA: 45%/ 27%/ 28%. SpA: 55% / 24%/ 21%. More
patients with PsA had PDQ score >18 compared to RA and SpA (p<0.001). For PDQ >
18 significantly higher scores were found for all patient reported outcomes and
disease activity scores. No clinical difference in CRP or swollen joint count was
found. Logistic regression showed increased odds for having VAS pain >=39 mm (the
median) for a PDQ-score >18 compared to <13 (OR = 10.4; 95%CI 8.6-12.5).
CONCLUSIONS: More than 50% of the Danish arthritis patients reported clinically
significant pain. More than 20% of the PDQ-completers had indication of
neuropathic pain features, which was related to a high pain-level. PDQ-score was
associated with DAS28-CRP and VAS pain but not with indicators of peripheral
inflammation (CRP and SJC). Thus, pain classification by PDQ may assist in
mechanism-based pain treatment.
PMID- 28686640
TI - Learning curve for laparoscopic Heller myotomy and Dor fundoplication for
achalasia.
AB - PURPOSE: Although laparoscopic Heller myotomy and Dor fundoplication (LHD) is
widely performed to address achalasia, little is known about the learning curve
for this technique. We assessed the learning curve for performing LHD. METHODS:
Of the 514 cases with LHD performed between August 1994 and March 2016, the
surgical outcomes of 463 cases were evaluated after excluding 50 cases with
reduced port surgery and one case with the simultaneous performance of
laparoscopic distal partial gastrectomy. A receiver operating characteristic
(ROC) curve analysis was used to identify the cut-off value for the number of
surgical experiences necessary to become proficient with LHD, which was defined
as the completion of the learning curve. RESULTS: We defined the completion of
the learning curve when the following 3 conditions were satisfied. 1) The
operation time was less than 165 minutes. 2) There was no blood loss. 3) There
was no intraoperative complication. In order to establish the appropriate number
of surgical experiences required to complete the learning curve, the cut-off
value was evaluated by using a ROC curve (AUC 0.717, p < 0.001). Finally, we
identified the cut-off value as 16 surgical cases (sensitivity 0.706, specificity
0.646). CONCLUSION: Learning curve seems to complete after performing 16 cases.
PMID- 28686641
TI - The prognostic importance of CXCR3 chemokine during organizing pneumonia on the
risk of chronic lung allograft dysfunction after lung transplantation.
AB - RATIONALE: Since the pathogenesis of chronic lung allograft dysfunction (CLAD)
remains poorly defined with no known effective therapies, the identification and
study of key events which increase CLAD risk is a critical step towards improving
outcomes. We hypothesized that bronchoalveolar lavage fluid (BALF) CXCR3 ligand
concentrations would be augmented during organizing pneumonia (OP) and that
episodes of OP with marked chemokine elevations would be associated with
significantly higher CLAD risk. METHODS: All transbronchial biopsies (TBBX) from
patients who received lung transplantation between 2000 to 2010 were reviewed.
BALF concentrations of the CXCR3 ligands (CXCL9, CXCL10 and CXCL11) were compared
between episodes of OP and "healthy" biopsies using linear mixed-effects models.
The association between CXCR3 ligand concentrations during OP and CLAD risk was
evaluated using proportional hazards models with time-dependent covariates.
RESULTS: There were 1894 bronchoscopies with TBBX evaluated from 441 lung
transplant recipients with 169 (9%) episodes of OP and 907 (49%) non-OP
histopathologic injuries. 62 (37%) episodes of OP were observed during routine
surveillance bronchoscopy. Eight hundred thirty-eight (44%) TBBXs had no
histopathology and were classified as "healthy" biopsies. There were marked
elevations in BALF CXCR3 ligand concentrations during OP compared with "healthy"
biopsies. In multivariable models adjusted for other injury patterns, OP did not
significantly increase the risk of CLAD when BAL CXCR3 chemokine concentrations
were not taken into account. However, OP with elevated CXCR3 ligands markedly
increased CLAD risk in a dose-response manner. An episode of OP with CXCR3
concentrations greater than the 25th, 50th and 75th percentiles had HRs for CLAD
of 1.5 (95% CI 1.0-2.3), 1.9 (95% CI 1.2-2.8) and 2.2 (95% CI 1.4-3.4),
respectively. CONCLUSIONS: This study identifies OP, a relatively uncommon
histopathologic finding after lung transplantation, as a major risk factor for
CLAD development when considered in the context of increased allograft expression
of interferon-gamma inducible ELR- CXC chemokines. We further demonstrate for the
first time, the prognostic importance of BALF CXCR3 ligand concentrations during
OP on subsequent CLAD risk.
PMID- 28686643
TI - Three-dimensional rotating flow of carbon nanotubes with Darcy-Forchheimer porous
medium.
AB - Here we are concerned with the Darcy-Forchheimer three-dimensional flow of carbon
nanotubes in a rotating frame. Flow is generated by stretching of the surface.
Xue model is adopted for nanofluid transport mechanism. Results for single wall
carbon nanotubes (SWCNTs) and multi wall carbon nanotubes are achieved and
compared. Flow saturating porous space obeys Darcy-Forchheimer expression.
Boundary layer approximations are invoked to simplify governing partial
differential system. Optimal homotopy analysis method (OHAM) is utilized for
solutions of governing model. The optimal values of auxiliary parameters are
computed. Plots have been displayed in order to analyze how the velocities and
temperature fields get affected by various flow parameters. Skin-friction
coefficients and local Nusselt number are presented through numerical data for
both SWCNTs and MWCNTs. Moreover the skin-friction coefficients and local Nusselt
number are enhanced for larger values of nanoparticles volume fraction.
PMID- 28686642
TI - Coding SNPs analysis highlights genetic relationships and evolution pattern in
eggplant complexes.
AB - Brinjal (Solanum melongena), scarlet (S. aethiopicum) and gboma (S. macrocarpon)
eggplants are three Old World domesticates. The genomic DNA of a collection of
accessions belonging to the three cultivated species, along with a representation
of various wild relatives, was characterized for the presence of single
nucleotide polymorphisms (SNPs) using a genotype-by-sequencing approach. A total
of 210 million useful reads were produced and were successfully aligned to the
reference eggplant genome sequence. Out of the 75,399 polymorphic sites
identified among the 76 entries in study, 12,859 were associated with coding
sequence. A genetic relationships analysis, supported by the output of the
FastSTRUCTURE software, identified four major sub-groups as present in the
germplasm panel. The first of these clustered S. aethiopicum with its wild
ancestor S. anguivi; the second, S. melongena, its wild progenitor S. insanum,
and its relatives S. incanum, S. lichtensteinii and S. linneanum; the third, S.
macrocarpon and its wild ancestor S. dasyphyllum; and the fourth, the New World
species S. sisymbriifolium, S. torvum and S. elaeagnifolium. By applying a
hierarchical FastSTRUCTURE analysis on partitioned data, it was also possible to
resolve the ambiguous membership of the accessions of S. campylacanthum, S.
violaceum, S. lidii, S. vespertilio and S. tomentsum, as well as to genetically
differentiate the three species of New World Origin. A principal coordinates
analysis performed both on the entire germplasm panel and also separately on the
entries belonging to sub-groups revealed a clear separation among species,
although not between each of the domesticates and their respective wild
ancestors. There was no clear differentiation between either distinct cultivar
groups or different geographical provenance. Adopting various approaches to
analyze SNP variation provided support for interpretation of results. The
genotyping-by-sequencing approach showed to be highly efficient for both
quantifying genetic diversity and establishing genetic relationships among and
within cultivated eggplants and their wild relatives. The relevance of these
results to the evolution of eggplants, as well as to their genetic improvement,
is discussed.
PMID- 28686644
TI - Physical activity and the mediating effect of fear, depression, anxiety, and
catastrophizing on pain related disability in people with chronic low back pain.
AB - BACKGROUND: Chronic low back pain is a worldwide burden that is not being abated
with our current knowledge and treatment of the condition. The fear-avoidance
model is used to explain the relationship between pain and disability in patients
with chronic low back pain. However there are gaps in empirical support for
pathways proposed within this model, and no evidence exists as to whether
physical activity moderates these pathways. METHODS: This was a cross-sectional
study of 218 people with chronic low back pain. Multiple mediation analyses were
conducted to determine the role of fear, catastrophizing, depression, and anxiety
in the relationship between pain and disability. Separate analyses were performed
with physical activity as the moderator. Individuals were classified as
performing regular structured physical activity if they described on average once
per week for > 30-minutes an activity classified at least moderate intensity (>=
4-6 METs), activity prescribed by an allied health professional for their back
pain, leisure time sport or recreation, or self-directed physical activity such
as resistance exercise. RESULTS: Fear, catastrophizing, and depression
significantly mediated the relationship between pain and disability (p<0.001).
However the mediating effect of catastrophizing was conditional upon weekly
physical activity. That is, the indirect effect for catastrophizing mediating the
relationship between pain and disability was only significant for individuals
reporting weekly physical activity (B = 1.31, 95% CI 0.44 to 2.23), compared to
individuals reporting no weekly physical activity (B = 0.21, 95% CI -0.50 to
0.97). Catastrophizing also mediated the relationship between pain and fear (B =
0.37, 95% CI 0.15 to 0.62), with higher scores explaining 53% of the total effect
of pain on fear. CONCLUSIONS: These results support previous findings about the
importance of fear and depression as factors that should be targeted in low back
pain patients to reduce back pain related disability. We have also extended
understanding for the mediating effect of catastrophizing on back pain related
disability. Back pain patients engaged with regular physical activity may require
counselling with regards to negative pain perceptions.
PMID- 28686646
TI - Cystic nodal metastasis in patients with oropharyngeal squamous cell carcinoma
receiving chemoradiotherapy: Relationship with human papillomavirus status and
failure patterns.
AB - OBJECTIVES: We investigated the relationships of cystic nodal metastasis, human
papillomavirus (HPV) status, and treatment failure patterns in patients with
oropharyngeal squamous cell carcinoma (OPSCC) treated with chemoradiotherapy.
METHODS: We retrospectively reviewed pretreatment MRI and clinical courses of
patients with OPSCC whose tumors were tested for HPV-induced p16 expression via
immunohistochemistry and who completed chemoradiotherapy. Cervical cystic nodal
metastasis and necrotic nodal metastasis were classified on MRI. RESULTS: Of 98
patients eligible for analysis, 33 were p16-positive. Cystic nodal metastasis was
significantly more prevalent in p16-positive than in p16-negative patients (39.4%
versus 18.5%, respectively; p = 0.025). Necrotic nodal metastasis was
significantly more prevalent in p16-negative than in p16-positive patients (73.8%
versus 51.5%, respectively; p = 0.027). On multivariate analysis, necrotic nodal
metastasis (odds ratio [OR] = 7.310, p = 0.011) was an independent predictor of
regional failure, while advanced nodal stage (OR = 4.119, p = 0.022) and cystic
nodal metastases (OR = 0.087, p = 0.026) were independent positive and negative
predictors of distant failure, respectively. CONCLUSIONS: Cervical cystic and
necrotic nodal metastases are associated with HPV-induced p16-positive and p16
negative OPSCC, respectively. Patients with necrotic nodal metastasis at
presentation have an increased risk of regional failure. Distant failure is
directly and inversely correlated with advanced nodal stage and cystic nodal
metastasis, respectively.
PMID- 28686647
TI - Diagnostic accuracy of ELISA for detecting serum Midkine in cancer patients.
AB - Midkine (MK) has been reported as the potential novel diagnostic biomarker for
cancer in several studies, but their results were controversial. Therefore, we
performed a diagnostic meta-analysis to assess the diagnostic value of serum MK
in cancer patients. A systematic electronic and manual search was performed for
relevant literatures through several databases up to June 1, 2017. The quality of
the studies included in the meta-analysis was assessed using the Quality
Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. All analyses were
conducted using stata12.0 software. Ten studies collectively included 1119 cancer
patients and 1441 controls met the eligible criteria. The summary estimates were:
sensitivity 0.78 (95% CI = 0.68-0.85), specificity 0.83 (95% CI = 0.72-0.90),
positive likelihood ratio 4,54 (95% CI = 2.64-7.80), negative likelihood 0.27
(95% CI = 0.18-0.40), diagnostic odds ratio 16.79 (95% CI = 7.17-39.33), and area
under the curve 0.87 (95% CI = 0.84-0.89). Publication bias was suggested by
Deeks' funnel plot asymmetry test (P = 0.92). According to our results, serum MK
has greater diagnostic value in diagnosing cancer, however, more reliable studies
in larger cohort should be conducted to evaluate the diagnostic accuracy of serum
MK.
PMID- 28686648
TI - Increased levels of soluble forms of E-selectin and ICAM-1 adhesion molecules
during human leptospirosis.
AB - Leptospirosis is a multisystemic zoonotic disease with infiltration of visceral
organs by Leptospira. The capacity of the vascular endothelium to grant immune
cell recruitment and activation in target organs during the disease course
remains poorly characterized. We ascertained the levels of expression of several
soluble cell adhesion molecules (CAM) notably expressed by endothelial cells in
human leptospirosis. We prospectively enrolled 20 hospitalized patients and
compared them to 10 healthy controls. Disease severity was defined by one or more
organ failures, or death. Plasmatic concentrations of soluble CAM were assessed
by multiplex bead assay at the time of patient presentation (M0) and 1 month
after hospital discharge. The levels of soluble E-selectin (sCD62E) and soluble
intercellular adhesion molecule 1 (sICAM-1, sCD53) were significantly increased
in patients compared to controls (p<0.0001) and at 1 month (p<0.0001) with median
values at 978 ng/ml (interquartile ranges 787-1164; sCD62E) and 1021 ng/ml (690
1428; sCD53). At M0, Soluble P-selectin level (sCD62P) was found to be decreased
with levels at 60 ng/ml (0-631) versus 711 ng/ml (343-1113) for healthy controls
(p<0.05). Levels of sICAM-3 (sCD50), sVCAM-1 (vascular cell adhesion molecule,
sCD106) and sPECAM-1 (platelet endothelial cell adhesion molecule, sCD31) were
not different from healthy subjects at M0. This study shows that two adhesion
molecules, shed as soluble forms, are elevated during the acute phase of
leptospirosis: E-selectin and s-ICAM1. These molecules may interfere with the
process of immune cell recruitment to clear Leptospira at tissue levels.
PMID- 28686649
TI - Survey on the levels of 25-hydroxy vitamin D and bone metabolic markers and
evaluation of their correlations with osteoporosis in perimenopausal woman in
Xi'an region.
AB - It has been accepted that vitamin D (VD) plays an important role in bone
metabolism. However, the levels of VD in people of different regions are quite
different and there is still no final conclusion on the significant correlation
between VD and osteoporosis. 245 cases of peri-menopausal women were collected to
study the relationship between VD and osteoporosis in western China. The mean
value of 25-hydroxyvitamin D for the participants was 14.39 ng/mL. The average
values of parathyroid hormone (PTH), calcium (Ca) and phosphorus (P) were 47.62
pg/mL, 2.26 mmol/L and 1.18 mmol/L, respectively. The average value of bone
mineral density (BMD) in lumbar vertebrae was -1.20 SD and that in femoral neck
was -0.04 SD. Compared with normal group, PTH of VD deficiency group was
significantly increased (P < 0.05), Ca was remarkably decreased (P < 0.01) while
the BMD between these two groups showed no significant difference (P > 0.05). VD
was in positive correlation with the age (P < 0.01) and Ca (< 0.01) of the
participants, negative correlation with PTH (P < 0.01) while no significant
correlation with the BMD of lumbar vertebrae and femoral neck (P > 0.05). The
risk factors resulting in the occurrence of osteoporosis in the lumbar vertebrae
of the participants covered Ca increase (OR = 66.247, P<0.05), age growth (OR =
1.194, P<0.01) and menopause (OR = 2.285, P<0.05). This study has found that the
status of VD deficiency showed no significant correlation with the level of BMD,
which hinted that independent measurement of the bone metabolic markers,
including Ca, P, VD and PTH, was difficult to accurately reflect the status of
BMD in peri-menopausal women of this region. It's necessary to combine multi-site
bone scanning to diagnose the patients' status of osteoporosis so as to provide
reasonable guidance for early clinical prevention and treatment.
PMID- 28686645
TI - Non-skeletal health effects of vitamin D supplementation: A systematic review on
findings from meta-analyses summarizing trial data.
AB - BACKGROUND: A large number of observational studies have reported harmful effects
of low 25-hydroxyvitamin D (25OHD) levels on non-skeletal outcomes. We performed
a systematic quantitative review on characteristics of randomized clinical trials
(RCTs) included in meta-analyses (MAs) on non-skeletal effects of vitamin D
supplementation. METHODS AND FINDINGS: We identified systematic reviews (SR)
reporting summary data in terms of MAs of RCTs on selected non-skeletal outcomes.
For each outcome, we summarized the results from available SRs and scrutinized
included RCTs for a number of predefined characteristics. We identified 54 SRs
including data from 210 RCTs. Most MAs as well as the individual RCTs reported
null-findings on risk of cardiovascular diseases, type 2 diabetes, weight-loss,
and malignant diseases. Beneficial effects of vitamin D supplementation was
reported in 1 of 4 MAs on depression, 2 of 9 MAs on blood pressure, 3 of 7 MAs on
respiratory tract infections, and 8 of 12 MAs on mortality. Most RCTs have
primarily been performed to determine skeletal outcomes, whereas non-skeletal
effects have been assessed as secondary outcomes. Only one-third of the RCTs had
low level of 25OHD as a criterion for inclusion and a mean baseline 25OHD level
below 50 nmol/L was only present in less than half of the analyses. CONCLUSIONS:
Published RCTs have mostly been performed in populations without low 25OHD
levels. The fact that most MAs on results from RCTs did not show a beneficial
effect does not disprove the hypothesis suggested by observational findings on
adverse health outcomes of low 25OHD levels.
PMID- 28686651
TI - A preliminary approach to quantifying the overall environmental risks posed by
development projects during environmental impact assessment.
AB - Environmental impact assessment (EIA) is used globally to manage the impacts of
development projects on the environment, so there is an imperative to demonstrate
that it can effectively identify risky projects. However, despite the widespread
use of quantitative predictive risk models in areas such as toxicology, ecosystem
modelling and water quality, the use of predictive risk tools to assess the
overall expected environmental impacts of major construction and development
proposals is comparatively rare. A risk-based approach has many potential
advantages, including improved prediction and attribution of cause and effect;
sensitivity analysis; continual learning; and optimal resource allocation. In
this paper we investigate the feasibility of using a Bayesian belief network
(BBN) to quantify the likelihood and consequence of non-compliance of new
projects based on the occurrence probabilities of a set of expert-defined
features. The BBN incorporates expert knowledge and continually improves its
predictions based on new data as it is collected. We use simulation to explore
the trade-off between the number of data points and the prediction accuracy of
the BBN, and find that the BBN could predict risk with 90% accuracy using
approximately 1000 data points. Although a further pilot test with real project
data is required, our results suggest that a BBN is a promising method to monitor
overall risks posed by development within an existing EIA process given a modest
investment in data collection.
PMID- 28686650
TI - Histopathological findings in colorectal liver metastases after
electrochemotherapy.
AB - Electrochemotherapy of colorectal liver metastases has been proven to be
feasible, safe and effective in a phase I/II study. In that study, a specific
group of patients underwent two-stage operation, and the detailed
histopathological evaluation of the resected tumors is presented here. Regressive
changes in electrochemotherapy-treated liver metastases were evaluated after the
second operation (in 8-10 weeks) in 7 patients and 13 metastases when the treated
metastases were resected. Macroscopic and microscopic changes were analyzed.
Electrochemotherapy induced coagulation necrosis in the treated area encompassing
both tumor and a narrow band of normal tissue. The area became necrotic,
encapsulated in a fibrous envelope while preserving the functionality of most of
the vessels larger than 5 mm in diameter and a large proportion of biliary
structures, but the smaller blood vessels displayed various levels of damage. At
the time of observation, 8-10 weeks after electrochemotherapy, regenerative
changes were already seen in the peripheral parts of the treated area. This study
demonstrates regressive changes in the whole electrochemotherapy-treated area of
the liver. Further evidence of disruption of vessels less than 5 mm in diameter
and preservation of the larger vessels by electrochemotherapy is provided. These
findings are important because electrochemotherapy has been indicated for the
therapy of metastases near major blood vessels in the liver to provide a safe
approach with good antitumor efficacy.
PMID- 28686652
TI - Differences in soil biological activity by terrain types at the sub-field scale
in central Iowa US.
AB - Soil microbial communities are structured by biogeochemical processes that occur
at many different spatial scales, which makes soil sampling difficult. Because
soil microbial communities are important in nutrient cycling and soil fertility,
it is important to understand how microbial communities function within the
heterogeneous soil landscape. In this study, a self-organizing map was used to
determine whether landscape data can be used to characterize the distribution of
microbial biomass and activity in order to provide an improved understanding of
soil microbial community function. Points within a row crop field in south
central Iowa were clustered via a self-organizing map using six landscape
properties into three separate landscape clusters. Twelve sampling locations per
cluster were chosen for a total of 36 locations. After the soil samples were
collected, the samples were then analysed for various metabolic indicators, such
as nitrogen and carbon mineralization, extractable organic carbon, microbial
biomass, etc. It was found that sampling locations located in the potholes and
toe slope positions had significantly greater microbial biomass nitrogen and
carbon, total carbon, total nitrogen and extractable organic carbon than the
other two landscape position clusters, while locations located on the upslope did
not differ significantly from the other landscape clusters. However, factors such
as nitrate, ammonia, and nitrogen and carbon mineralization did not differ
significantly across the landscape. Overall, this research demonstrates the
effectiveness of a terrain-based clustering method for guiding soil sampling of
microbial communities.
PMID- 28686653
TI - Ribbon scanning confocal for high-speed high-resolution volume imaging of brain.
AB - Whole-brain imaging is becoming a fundamental means of experimental insight;
however, achieving subcellular resolution imagery in a reasonable time window has
not been possible. We describe the first application of multicolor ribbon
scanning confocal methods to collect high-resolution volume images of chemically
cleared brains. We demonstrate that ribbon scanning collects images over ten
times faster than conventional high speed confocal systems but with equivalent
spectral and spatial resolution. Further, using this technology, we reconstruct
large volumes of mouse brain infected with encephalitic alphaviruses and
demonstrate that regions of the brain with abundant viral replication were
inaccessible to vascular perfusion. This reveals that the destruction or collapse
of large regions of brain micro vasculature may contribute to the severe disease
caused by Venezuelan equine encephalitis virus. Visualization of this fundamental
impact of infection would not be possible without sampling at subcellular
resolution within large brain volumes.
PMID- 28686655
TI - SOTXTSTREAM: Density-based self-organizing clustering of text streams.
AB - A streaming data clustering algorithm is presented building upon the density
based self-organizing stream clustering algorithm SOSTREAM. Many density-based
clustering algorithms are limited by their inability to identify clusters with
heterogeneous density. SOSTREAM addresses this limitation through the use of
local (nearest neighbor-based) density determinations. Additionally, many stream
clustering algorithms use a two-phase clustering approach. In the first phase, a
micro-clustering solution is maintained online, while in the second phase, the
micro-clustering solution is clustered offline to produce a macro solution. By
performing self-organization techniques on micro-clusters in the online phase,
SOSTREAM is able to maintain a macro clustering solution in a single phase.
Leveraging concepts from SOSTREAM, a new density-based self-organizing text
stream clustering algorithm, SOTXTSTREAM, is presented that addresses several
shortcomings of SOSTREAM. Gains in clustering performance of this new algorithm
are demonstrated on several real-world text stream datasets.
PMID- 28686654
TI - A retrospective case-cohort study comparing treatment outcomes in abacavir versus
stavudine containing first line antiretroviral treatment regimens in children
<3yrs old, at a paediatric programme based in Soweto, South Africa.
AB - INTRODUCTION: The current World Health Organization guideline for first line
antiretroviral therapy (ART) in HIV-infected children recommends the use of
abacavir and lamivudine as nucleoside backbones and no longer includes stavudine.
We compared treatment outcomes with abacavir (ABC) versus stavudine (d4T) in a
cohort of HIV-1 infected children 6 and 12 months after antiretroviral therapy
was initiated. METHODS: This was a retrospective case-cohort study, using
programmatic data from children enrolled in the Paediatric Wellness Programme at
the Perinatal HIV Research Unit in Soweto, South Africa between 2005 and 2013.
Children on abacavir/stavudine who had initiated ART at age <3 years with a
regimen including lamivudine and lopinavir/ritonavir and had at least one 6 or 12
month viral load result were eligible. All ABC cases identified were matched for
age at ART initiation and gender to eligible d4T controls (1:2). Outcomes
analysed at 6 and 12 months post ART initiation included virological failure,
mortality, immunological failure and anthropometry. Chi-square tests compared
categorical measures while Kruskal-Wallis compared continuous measures. RESULTS:
We identified 57 eligible ABC cases and selected 114 matched d4T controls.
Overall, 57% were females and 89% started treatment at age <1year. The median age
at ART initiation was 3.11 (IQR: 1.98-6.05) months. There was no difference in
the proportion of children virologically suppressed between the groups at 6 (ABC
54.5% vs. d4T 67.0%, p = 0.125) and 12 (ABC 66.7% vs. d4T 71.6%, p = 0.53) months
post ART-initiation. The proportion of children with adherence levels >90% for
ABC and d4T were similar too (95% in ABC vs. 86% in d4T, p = 0.10). The
proportion of children who died over 12 months was 3.5% in the ABC and 7.9% in
the d4T group (p = 0.27). Similarly, the anthropometric measures were comparable.
CONCLUSIONS: It is reassuring that in the short term, in this group of patients,
the treatment outcomes were similar.
PMID- 28686656
TI - Avoiding fears and promoting shared decision-making: How should physicians inform
patients about radiation exposure from imaging tests?
AB - OBJECTIVE: We aimed to evaluate the population's awareness about the radiation
exposure associated with five specific imaging tests, and their preference
regarding three different formats for receiving the information before undergoing
an imaging test. METHODS: A quantitative and qualitative evaluation through a
survey and focal groups including general population from two health departments
in Spain. The sampling was carried out in stages (according to health department
size) and stratified by age and sex, to get a representative sample. We randomly
selected the participants from these stages to be contacted by telephone by a
trained nurse. Oral informed consent was obtained. RESULTS: Of 602 participants
in the quantitative survey, 418 (70.3%) stated that they were aware of the risk
associated with radiation. While the majority of these 418 participants knew that
x-rays involve radiation (85.4%), fewer were aware that CT (42%) and mammography
(38%) also involve radiation, and a substantial proportion believed, incorrectly,
that MRI (38%) and ultrasound (18.4%) expose patients to radiation. The
population preference was to receive the information using both oral and written
formats, accompanied by a table showing the equivalence of the radiation
associated with the imaging test to either a number of chest X-rays and exposure
number of days of background radiation. DISCUSSION: The general population does
not receive enough information regarding radiation exposure and the associated
risks related to imaging tests. Initiatives should be designed to reinforce the
patient's awareness when ordering a diagnostic imaging test.
PMID- 28686657
TI - Phase I randomized clinical trial of N-acetylcysteine in combination with an
adjuvant probenecid for treatment of severe traumatic brain injury in children.
AB - BACKGROUND: There are no therapies shown to improve outcome after severe
traumatic brain injury (TBI) in humans, a leading cause of morbidity and
mortality. We sought to verify brain exposure of the systemically administered
antioxidant N-acetylcysteine (NAC) and the synergistic adjuvant probenecid, and
identify adverse effects of this drug combination after severe TBI in children.
METHODS: IRB-approved, randomized, double-blind, placebo controlled Phase I study
in children 2 to 18 years-of-age admitted to a Pediatric Intensive Care Unit
after severe TBI (Glasgow Coma Scale [GCS] score <=8) requiring an externalized
ventricular drain for measurement of intracranial pressure (ICP). Patients were
recruited from November 2011-August 2013. Fourteen patients (n = 7/group) were
randomly assigned after obtaining informed consent to receive probenecid (25
mg/kg load, then 10 mg/kg/dose q6h*11 doses) and NAC (140 mg/kg load, then 70
mg/kg/dose q4h*17 doses), or placebos via naso/orogastric tube. Serum and CSF
samples were drawn pre-bolus and 1-96 h after randomization and drug
concentrations were measured via UPLC-MS/MS. Glasgow Outcome Scale (GOS) score
was assessed at 3 months. RESULTS: There were no adverse events attributable to
drug treatment. One patient in the placebo group was withdrawn due to adverse
effects. In the treatment group, NAC concentrations ranged from 16,977.3+/
2,212.3 to 16,786.1+/-3,285.3 in serum and from 269.3+/-113.0 to 467.9+/-262.7
ng/mL in CSF, at 24 to 72 h post-bolus, respectively; and probenecid
concentrations ranged from 75.4.3+/-10.0 to 52.9+/-25.8 in serum and 5.4+/-1.0 to
4.6+/-2.1 MUg/mL in CSF, at 24 to 72 h post-bolus, respectively (mean+/-SEM).
Temperature, mean arterial pressure, ICP, use of ICP-directed therapies,
surveillance serum brain injury biomarkers, and GOS at 3 months were not
different between groups. CONCLUSIONS: Treatment resulted in detectable
concentrations of NAC and probenecid in CSF and was not associated with
undesirable effects after TBI in children. TRIAL REGISTRATION: ClinicalTrials.gov
NCT01322009.
PMID- 28686658
TI - A hypoxia response element in the Vegfa promoter is required for basal Vegfa
expression in skin and for optimal granulation tissue formation during wound
healing in mice.
AB - Hypoxia in skin wounds is thought to contribute to healing through the induction
of hypoxia inducible factor-1 (HIF-1). Although HIF-1 can regulate the expression
of vascular endothelial growth factor A (Vegfa), whether hypoxia and HIF-1 are
required to induce Vegfa expression in the context of wound healing is unknown.
To test this hypothesis, we evaluated Vegfa expression and wound healing in
mutant mice that lack a functional HIF-1 binding site in the Vegfa promoter. Full
thickness excisional wounds were made using a biopsy punch, left to heal by
second intention, and granulation tissue isolated on a time course during
healing. mRNA levels of Vegfa and its target genes platelet-derived growth
factors B (Pdgfb) and stromal cell-derived factor-1 (Sdf1) were measured by RT
qPCR, and HIF-1alpha and VEGFA protein levels measured by immunoblotting. Lower
levels of Vegfa, Pdgf1 and Sdf1 mRNA were found in intact skin of mutant mice
relative to wild-type controls (n = 6 mice/genotype), whereas levels in
granulation tissue during wound healing were unaltered. VEGFA protein levels were
also lower in intact skin of the mutant versus the wild-type mice. Decreased
Vegfa mRNA levels in skin of mutant mice could not be attributed to decreased HIF
1alpha protein expression, and were therefore a consequence of the loss of HIF-1
responsiveness of the Vegfa promoter. Comparative histologic analyses of healing
wounds in mutant and wild-type mice (n = 8 mice/genotype) revealed significant
defects in granulation tissue in the mutant mice, both in terms of quantity and
capillary density, although epithelialization and healing rates were unaltered.
We conclude that HIF-1 is not a major regulator of Vegfa expression during wound
healing; rather, it serves to maintain basal levels of expression of Vegfa and
its target genes in intact skin, which are required for optimal granulation
tissue formation in response to wounding.
PMID- 28686659
TI - Clearing muddied waters: Capture of environmental DNA from turbid waters.
AB - Understanding the differences in efficiencies of various methods to concentrate,
extract, and amplify environmental DNA (eDNA) is vital for best performance of
eDNA detection. Aquatic systems vary in characteristics such as turbidity, eDNA
concentration, and inhibitor load, thus affecting eDNA capture efficiency.
Application of eDNA techniques to the detection of terrestrial invasive or
endangered species may require sampling at intermittent water sources that are
used for drinking and cooling; these water bodies may often be stagnant and
turbid. We present our best practices technique for the detection of wild pig
eDNA in water samples, a protocol that will have wide applicability to the
detection of elusive vertebrate species. We determined the best practice for eDNA
capture in a turbid water system was to concentrate DNA from a 15 mL water sample
via centrifugation, purify DNA with the DNeasy mericon Food kit, and remove
inhibitors with Zymo Inhibitor Removal Technology columns. Further, we compared
the sensitivity of conventional PCR to quantitative PCR and found that
quantitative PCR was more sensitive in detecting lower concentrations of eDNA. We
show significant differences in efficiencies among methods in each step of eDNA
capture, emphasizing the importance of optimizing best practices for the system
of interest.
PMID- 28686660
TI - Species diversity and chemical properties of litter influence non-additive
effects of litter mixtures on soil carbon and nitrogen cycling.
AB - Decomposition of litter mixtures generally cannot be predicted from the component
species incubated in isolation. Therefore, such non-additive effects of litter
mixing on soil C and N dynamics remain poorly understood in terrestrial
ecosystems. In this study, litters of Mongolian pine and three dominant
understory species and soil were collected from a Mongolian pine plantation in
Northeast China. In order to examine the effects of mixed-species litter on soil
microbial biomass N, soil net N mineralization and soil respiration, four single
litter species and their mixtures consisting of all possible 2-, 3- and 4-species
combinations were added to soils, respectively. In most instances, species mixing
produced synergistic non-additive effects on soil microbial biomass N and soil
respiration, but antagonistic non-additive effects on net N mineralization.
Species composition rather than species richness explained the non-additive
effects of species mixing on soil microbial biomass N and net N mineralization,
due to the interspecific differences in litter chemical composition. Both litter
species composition and richness explained non-additive soil respiration
responses to mixed-species litter, while litter chemical diversity and chemical
composition did not. Our study indicated that litter mixtures promoted soil
microbial biomass N and soil respiration, and inhibited net N mineralization.
Soil N related processes rather than soil respiration were partly explained by
litter chemical composition and chemical diversity, highlighting the importance
of functional diversity of litter on soil N cycling.
PMID- 28686661
TI - Engineering of monobody conjugates for human EphA2-specific optical imaging.
AB - In a previous study, we developed an E1 monobody specific for the tumor biomarker
hEphA2 [PLoS ONE (2015) 10(7): e0132976]. E1 showed potential as a molecular
probe for in vitro and in vivo targeting of cancers overexpressing hEphA2. In the
present study, we constructed expression vectors for E1 conjugated to optical
reporters such as Renilla luciferase variant 8 (Rluc8) or enhanced green
fluorescent protein (EGFP) and purified such recombinant proteins by affinity
chromatography in E. coli. E1-Rluc8 and E1-EGFP specifically bound to hEphA2 in
human prostate cancer PC3 cells but not in human cervical cancer HeLa cells,
which express hEphA2 at high and low levels, respectively. These recombinant
proteins maintained >40% activity in mouse serum at 24 h. In vivo optical imaging
for 24 h did not detect E1-EGFP signals, whereas E1-Rluc8 showed tumor-specific
luminescence signals in PC3 but not in HeLa xenograft mice. E1-Rluc8 signals were
detected at 4 h, peaked at 12 h, and were undetectable at 24 h. These results
suggest the potential of E1-Rluc8 as an EphA2-specific optical imaging agent.
PMID- 28686662
TI - Comparison of a new multiplex real-time PCR with the Kato Katz thick smear and
copro-antigen ELISA for the detection and differentiation of Taenia spp. in human
stools.
AB - BACKGROUND: Taenia solium, the cause of neurocysticercosis (NCC), has significant
socioeconomic impacts on communities in developing countries. This disease, along
with taeniasis is estimated to infect 2.5 to 5 million people globally. Control
of T. solium NCC necessitates accurate diagnosis and treatment of T. solium
taeniasis carriers. In areas where all three species of Taenia tapeworms (T.
solium, Taenia saginata and Taenia asiatica) occur sympatrically, conventional
microscope- and copro-antigen based diagnostic methods are unable to distinguish
between these three Taenia species. Molecular diagnostic tools have been
developed to overcome this limitation; however, conventional PCR-based techniques
remain unsuitable for large-scale deployment in community-based surveys.
Moreover, a real-time PCR (qPCR) for the discrimination of all three species of
Taenia in human stool does not exist. This study describes the development and
validation of a new triplex Taq-Man probe-based qPCR for the detection and
discrimination of all three Taenia human tapeworms in human stools collected from
communities in the Central Highlands of Vietnam. The diagnostic characteristics
of the test are compared with conventional Kato Katz (KK) thick smear and copro
antigen ELISA (cAgELISA) method utilizing fecal samples from a community based
cross-sectional study. Using this new multiplex real-time PCR we provide an
estimate of the true prevalence of taeniasis in the source population for the
community based cross-sectional study. METHODOLOGY/PRINCIPAL FINDINGS: Primers
and TaqMan probes for the specific amplification of T. solium, T. saginata and T.
asiatica were designed and successfully optimized to target the internal
transcribed spacer I (ITS-1) gene of T. solium and the cytochrome oxidase subunit
I (COX-1) gene of T. saginata and T. asiatica. The newly designed triplex qPCR
(T3qPCR) was compared to KK and cAgELISA for the detection of Taenia eggs in
stool samples collected from 342 individuals in Dak Lak province, Central
Highlands of Vietnam. The overall apparent prevalence of taeniasis in Dak Lak
province was 6.72% (95% confidence interval (CI) [3.94-9.50]) in which T. solium
accounted for 1.17% (95% CI [0.37-3.17]), according to the T3qPCR. There was
sympatric presence of T. solium, T. saginata and T. asiatica. The T3qPCR proved
superior to KK and cAgELISA for the detection and differentiation of Taenia
species in human feces. Diagnostic sensitivities of 0.94 (95% credible interval
(CrI) [0.88-0.98]), 0.82 (95% CrI [0.58-0.95]) and 0.52 (95% CrI [0.07-0.94]),
and diagnostic specificities of 0.98 (95% CrI [0.94-1.00]), 0.91 (95% CrI [0.85
0.96]) and 0.99 (95% CrI [0.96-1.00]) were estimated for the diagnosis of
taeniasis for the T3qPCR, cAgELISA and KK thick smear in this study,
respectively. CONCLUSIONS: T3qPCR is not only superior to the KK thick smear and
cAgELISA in terms of diagnostic sensitivity and specificity, but it also has the
advantage of discriminating between species of Taenia eggs in stools. Application
of this newly developed T3qPCR has identified the existence of all three human
Taenia tapeworms in Dak Lak province and proves for the first time, the existence
of T. asiatica in the Central Highlands and the south of Vietnam.
PMID- 28686663
TI - In-vitro release pharmacokinetics of amikacin, teicoplanin and polyhexanide in a
platelet rich fibrin-layer (PRF)-a laboratory evaluation of a modern, autologous
wound treatment.
AB - OBJECTIVES: Platelet rich fibrin (PRF) is an autologous fibrin glue, produced
from patients' blood, which, besides intraoperative use, has applications in the
treatment of infected wounds. The combination with antimicrobial agents results
in a prolonged antibacterial effect allowing for wound dressing change intervals
of seven days even in infected wounds. The aim of this study was to evaluate
release kinetics of amikacin, teicoplanin or polyhexanide from a PRF-layer.
METHODS: PRF mixed with teicoplanin, amikacin or polyhexanide was sprayed on a
silicon gauze patch and put on a colombia agar with bacteria with known minimal
inhibitory concentration (MIC) and incubated for 24 hours and afterwards
transferred to another agar with the same bacterial strain. Inhibition zones were
measured every 24 hours. This was repeated on 7 consecutive days. Antibiotic
concentrations were calculated by interpolation. RESULTS: More than 1000 mg/L
teicoplanin were released within the first 24 hours and 28.22 mg/L after 168
hours. Amikacin release was above 10,000 mg/L within the first 24 hours and still
120.8 mg/L after 120 hours. A release of polyhexanide could be verified for the
first 24 hours only. Consequently teicoplanin and amikacin released from PRF
showed antimicrobial in-vitro effects for almost a week, whereas an antimicrobial
effect of polyhexanide could only be verified for the first 24 hours.
CONCLUSIONS: Our Results show that a weekly dressing regimen may be justified in
wounds treated with PRF plus amikacin or teicoplanin, since bacteria will be
eradicated over a considerable period of time after a single application of PRF.
PMID- 28686664
TI - Somatosensory function in patients with secondary adrenal insufficiency treated
with two different doses of hydrocortisone-Results from a randomized controlled
trial.
AB - BACKGROUND: Low cortisol levels are associated with several functional pain
syndromes. In patients with secondary adrenal insufficiency (SAI), the lack in
endogenous cortisol production is substituted by the administration of oral
hydrocortisone (HC). Our previous study showed that a lower dose of HC led to an
increase in reported subjective pain symptoms. Whether different doses of HC
substitution alter somatosensory functioning in SAI patients has not been
established yet. METHODS: In this randomized double blind cross-over trial, forty
six patients with SAI participated. Patients randomly received either first a
lower dose (0.2-0.3 mg HC/kg body weight/day) for 10 weeks followed by a higher
dose (0.4-0.6 mg HC/kg body weight/day) for another 10 weeks, or vice versa.
After each treatment period, blood samples were drawn and somatosensory
functioning was assessed by determining the mechanical detection threshold (MDT),
mechanical pain threshold (MPT), mechanical pain sensitivity (MPS) and the pain
pressure threshold (PPT), according to the Quantitative Sensory Testing (QST)
battery by the German Network on Neuropathic Pain. RESULTS: The administration of
the higher dose of HC resulted in significantly higher levels of cortisol (mean
[SD] 748 [245] nmol/L) than the lower dose (537 [250] nmol/L, P<0.001). No
differences were found in MDT, MPT, MPS and PPT z-scores between the two doses of
HC. Furthermore, the number of patients showing sensory abnormalities did not
differ between the two different doses. CONCLUSIONS: The results suggest that the
dose of HC has no impact on somatosensory functioning in response to mechanical
stimuli in patients with SAI, despite previously found altered subjective pain
reports.
PMID- 28686665
TI - The esperanza window trap reduces the human biting rate of Simulium ochraceum
s.l. in formerly onchocerciasis endemic foci in Southern Mexico.
AB - BACKGROUND: The Esperanza Window Trap (EWT) baited with CO2 and human sweat
compounds is attractive to Simulium ochraceum s.l., the primary vector of
Onchocerca volvulus in the historically largest endemic foci in Mexico and
Guatemala. METHODOLOGY/PRINCIPAL FINDINGS: The ability of the EWT to locally
reduce numbers of questing S. ochraceum s.l. was evaluated in two formerly
onchocerciasis endemic communities in Southern Mexico. At each community, two
EWTs were placed in or near a school or household and flies were collected
sequentially for a total of 10 days. Black fly collections were then carried out
for an additional 10 days in the absence of the EWTs. Flies were also collected
outside the dwellings to control for variations in the local fly populations.
When the EWTs were present, there was a significant reduction in the human biting
rate at both the household and school locations at collection sites, with a
greater effect observed in the schools. CONCLUSIONS/SIGNIFICANCE: These results
indicate that the EWTs not only have potential as a black fly monitoring tool but
may be used for reducing personal exposure to fly bites in Mesoamerica.
PMID- 28686666
TI - The nature of the GRE influences the screening for GR-activity enhancing
modulators.
AB - Glucocorticoid resistance (GCR), i.e. unresponsiveness to the beneficial anti
inflammatory activities of the glucocorticoid receptor (GR), poses a serious
problem in the treatment of inflammatory diseases. One possible solution to try
and overcome GCR, is to identify molecules that prevent or revert GCR by hyper
stimulating the biological activity of the GR. To this purpose, we screened for
compounds that potentiate the dexamethasone (Dex)-induced transcriptional
activity of GR. To monitor GR transcriptional activity, the screen was performed
using the lung epithelial cell line A549 in which a glucocorticoid responsive
element (GRE) coupled to a luciferase reporter gene construct was stably
integrated. Histone deacetylase inhibitors (HDACi) such as Vorinostat and
Belinostat are two broad-spectrum HDACi that strongly increased the Dex-induced
luciferase expression in our screening system. In sharp contrast herewith,
results from a genome-wide transcriptome analysis of Dex-induced transcripts
using RNAseq, revealed that Belinostat impairs the ability of GR to transactivate
target genes. The stimulatory effect of Belinostat in the luciferase screen
further depends on the nature of the reporter construct. In conclusion, a
profound discrepancy was observed between HDACi effects on two different
synthetic promoter-luciferase reporter systems. The favorable effect of HDACi on
gene expression should be evaluated with care, when considering them as potential
therapeutic agents. GEO accession number GSE96649.
PMID- 28686667
TI - Quantitative assessments of water-use efficiency in Temperate Eurasian Steppe
along an aridity gradient.
AB - Water-use efficiency (WUE), defined as the ratio of net primary productivity
(NPP) to evapotranspiration (ET), is an important indicator to represent the
trade-off pattern between vegetation productivity and water consumption. Its
dynamics under climate change are important to ecohydrology and ecosystem
management, especially in the drylands. In this study, we modified and used a
late version of Boreal Ecosystem Productivity Simulator (BEPS), to quantify the
WUE in the typical dryland ecosystems, Temperate Eurasian Steppe (TES). The
Aridity Index (AI) was used to specify the terrestrial water availability
condition. The regional results showed that during the period of 1999-2008, the
WUE has a clear decreasing trend in the spatial distribution from arid to humid
areas. The highest annual average WUE was in dry and semi-humid sub-region (DSH)
with 0.88 gC mm-1 and the lowest was in arid sub-region (AR) with 0.22 gC mm-1. A
two-stage pattern of WUE was found in TES. That is, WUE would enhance with lower
aridity stress, but decline under the humid environment. Over 65% of the region
exhibited increasing WUE. This enhancement, however, could not indicate that the
grasslands were getting better because the NPP even slightly decreased. It was
mainly attributed to the reduction of ET over 70% of the region, which is closely
related to the rainfall decrease. The results also suggested a similar negative
spatial correlation between the WUE and the mean annual precipitation (MAP) at
the driest and the most humid ends. This regional pattern reflected the different
roles of water in regulating the terrestrial ecosystems under different aridity
levels. This study could facilitate the understanding of the interactions between
terrestrial carbon and water cycles, and thus contribute to a sustainable
management of nature resources in the dryland ecosystems.
PMID- 28686670
TI - Correction: Immuno-related polymorphisms and cervical cancer risk: The IARC
multicentric case-control study.
AB - [This corrects the article DOI: 10.1371/journal.pone.0177775.].
PMID- 28686668
TI - Molecular interactions of EphA4, growth hormone receptor, Janus kinase 2, and
signal transducer and activator of transcription 5B.
AB - We previously reported that EphA4, a member of the Eph family of receptor
tyrosine kinases, is an important modulator of growth hormone (GH) signaling,
leading to augmented synthesis of insulin-like growth factor 1 (IGF1) for
postnatal body growth. In the present study, we report the molecular interactions
of EphA4, GH receptor (GHR), Janus kinase 2 (JAK2), and signal transducer and
activator of transcription 5B (STAT5B). EphA4 binds to GHR at both its
extracellular and intracellular domains and phosphorylates GHR when stimulated
with a ligand. The cytoplasmic domain of EphA4 binds to the carboxy-terminus of
JAK2 in contrast to the known binding of GHR to the amino-terminus. STAT5B binds
to the amino-terminal kinase domain of EphA4. Ligand-activated EphA4 and JAK2
phosphorylate each other and STAT5B, but JAK2 does not appear to phosphorylate
EphA4-bound STAT5B. Ligand-activated EphA4 induces the nuclear translocation of
STAT5B in a JAK2-independent manner. GHR expression is required for the
activation of STAT5B signaling, even via the JAK2-independent pathway. Various
ephrins that have affinity for EphA4 induce STAT5B phosphorylation. These
findings suggest the molecular mechanisms by which ephrin/EphA4 signaling
enhances the canonical GH-IGF1 axis.
PMID- 28686669
TI - Obesity/Type II diabetes alters macrophage polarization resulting in a fibrotic
tendon healing response.
AB - Type II Diabetes (T2DM) dramatically impairs the tendon healing response,
resulting in decreased collagen organization and mechanics relative to non
diabetic tendons. Despite this burden, there remains a paucity of information
regarding the mechanisms that govern impaired healing of diabetic tendons. Mice
were placed on either a high fat diet (T2DM) or low fat diet (lean) and underwent
flexor tendon transection and repair surgery. Healing was assessed via mechanical
testing, histology and changes in gene expression associated with collagen
synthesis, matrix remodeling, and macrophage polarization. Obese/diabetic tendons
healed with increased scar formation and impaired mechanical properties.
Consistent with this, prolonged and excess expression of extracellular matrix
(ECM) components were observed in obese/T2DM tendons. Macrophages are involved in
both inflammatory and matrix deposition processes during healing. Obese/T2DM
tendons healed with increased expression of markers of pro-inflammatory M1
macrophages, and elevated and prolonged expression of M2 macrophages markers that
are involved in ECM deposition. Here we demonstrate that tendons from
obese/diabetic mice heal with increased scar formation and increased M2
polarization, identifying excess M2 macrophage activity and matrix synthesis as a
potential mechanism of the fibrotic healing phenotype observed in T2DM tendons,
and as such a potential target to improve tendon healing in T2DM.
PMID- 28686671
TI - Assessment of circulating copy number variant detection for cancer screening.
AB - Current high-sensitivity cancer screening methods, largely utilizing correlative
biomarkers, suffer from false positive rates that lead to unnecessary medical
procedures and debatable public health benefit overall. Detection of circulating
tumor DNA (ctDNA), a causal biomarker, has the potential to revolutionize cancer
screening. Thus far, the majority of ctDNA studies have focused on detection of
tumor-specific point mutations after cancer diagnosis for the purpose of post
treatment surveillance. However, ctDNA point mutation detection methods developed
to date likely lack either the scope or analytical sensitivity necessary to be
useful for cancer screening, due to the low (<1%) ctDNA fraction derived from
early stage tumors. On the other hand, tumor-derived copy number variant (CNV)
detection is hypothetically a superior means of ctDNA-based cancer screening for
many tumor types, given that, relative to point mutations, each individual tumor
CNV contributes a much larger number of ctDNA fragments to the overall pool of
circulating free DNA (cfDNA). A small number of studies have demonstrated the
potential of ctDNA CNV-based screening in select cancer types. Here we perform an
in silico assessment of the potential for ctDNA CNV-based cancer screening across
many common cancers, and suggest ctDNA CNV detection shows promise as a broad
cancer screening methodology.
PMID- 28686672
TI - Late Miocene Pseudolarix amabilis bract-scale complex from Zhejiang, East China.
AB - Previously, the identification of fossil Pseudolarix at the species level has
been based on the morphology of the bract-scale complex of the seed cone. The
morphological consistence of fossils through most of the Cenozoic with extant P.
amabilis has led them to be considered conspecific, suggesting that P. amabilis
is an extraordinary example of morphological stasis. However, the lack of
cuticular evidence, especially for the leaf-homologous bract, reduces the
accuracy of fossil identification based on morphology, thus weakening the
evidence for morphological stasis in P. amabilis. For the first time, we provide
cuticular evidence of the bract-scale of fossil P. amabilis based on the bract
scale complex from the late Miocene Shengxian Formation, Zhejiang, East China,
which improves the identification accuracy and reinforces the concept of
morphological stasis in this species. Second, we preliminarily reveal the niche
stability of P. amabilis, which corresponds to its morphological stasis. Finally,
we infer that the late Miocene forest containing P. amabilis in Zhejiang was an
evergreen sclerophyllous broad-leaved or mixed mesophytic forest, which combined
with the evergreen broad-leaved forest suggested by previous megafossil studies,
indicates the occurrence of vertical vegetation zonation.
PMID- 28686673
TI - Focal areas of increased lipid concentration on the coating of microbubbles
during short tone-burst ultrasound insonification.
AB - Acoustic behavior of lipid-coated microbubbles has been widely studied, which has
led to several numerical microbubble dynamics models that incorporate lipid
coating behavior, such as buckling and rupture. In this study we investigated the
relationship between microbubble acoustic and lipid coating behavior on a
nanosecond scale by using fluorescently labeled lipids. It is hypothesized that a
local increased concentration of lipids, appearing as a focal area of increased
fluorescence intensity (hot spot) in the fluorescence image, is related to
buckling and folding of the lipid layer thereby highly influencing the
microbubble acoustic behavior. To test this hypothesis, the lipid microbubble
coating was fluorescently labeled. The vibration of the microbubble (n = 177; 2.3
10.3 MUm in diameter) upon insonification at an ultrasound frequency of 0.5 or 1
MHz at 25 or 50 kPa acoustic pressure was recorded with the UPMC Cam, an ultra
high-speed fluorescence camera, operated at ~4-5 million frames per second.
During short tone-burst excitation, hot spots on the microbubble coating occurred
at relative vibration amplitudes > 0.3 irrespective of frequency and acoustic
pressure. Around resonance, the majority of the microbubbles formed hot spots.
When the microbubble also deflated acoustically, hot spot formation was likely
irreversible. Although compression-only behavior (defined as substantially more
microbubble compression than expansion) and subharmonic responses were observed
in those microbubbles that formed hot spots, both phenomena were also found in
microbubbles that did not form hot spots during insonification. In conclusion,
this study reveals hot spot formation of the lipid monolayer in the microbubble's
compression phase. However, our experimental results show that there is no direct
relationship between hot spot formation of the lipid coating and microbubble
acoustic behaviors such as compression-only and the generation of a subharmonic
response. Hence, our hypothesis that hot spots are related to acoustic buckling
could not be verified.
PMID- 28686675
TI - Management of flu-like syndrome with cetirizine in patients with relapsing
remitting multiple sclerosis during therapy with interferon beta: Results of a
randomized, cross-over, placebo-controlled pilot study.
AB - BACKGROUND: Flu-like syndrome (FLS) is a common adverse event experienced by
patients with relapsing-remitting multiple sclerosis (RRMS) treated with
interferon beta (IFNbeta). FLS can lead to poor treatment adherence and early
IFNbeta discontinuation. The involvement of interleukin-6 (IL-6) in the
occurrence of FLS has been suggested. We hypothesized that cetirizine, a second
generation histamine H1 receptor antagonist able to reduce the levels of IL-6,
might improve IFNbeta-induced FLS. METHODS: We conducted a pilot, cross-over,
randomized, placebo-controlled, double-blind study to evaluate the efficacy of
cetirizine 10 mg added after each IFNbeta injection to the standard of care for
FLS (acetaminophen or nonsteroidal anti-inflammatory drugs) on FLS in patients
with RRMS treated with IFNbeta. Patients were randomized to two treatment
sequences: 1) 4-week treatment with placebo added to the standard treatment for
FLS, followed by 4-week treatment with cetirizine added to the standard of care,
and 2) first addition of cetirizine, then of placebo. The primary efficacy
endpoint was the mean change of FLS severity [11-point visual analog scale (VAS)]
after 4 weeks of treatment within each sequence. RESULTS: Forty-five patients
(71.1% female, mean age 39.1 years, mean time from RRMS diagnosis 5.8 years) were
randomized to treatment sequences 1 and 2. The differences between cetirizine and
placebo in the intensity of FLS were not statistically significant: total mean
VAS scores at 4 hours from IFNbeta injection were 3.57 and 3.42 for cetirizine
and placebo, respectively (difference -0.15; 95% confidence interval: from -0.74
to 0.44; p = 0.6029). The two treatments were similar also with regard to other
efficacy measures considered and to the safety/tolerability profile. CONCLUSIONS:
The addition of cetirizine to the standard of care for IFNbeta-induced FLS in
patients with RRMS does not seem to provide significant benefits compared with
placebo. Further effort is required to understand the mechanisms underlying
IFNbeta-induced FLS. TRIAL REGISTRATION: EudraCT 2013-001055-12.
PMID- 28686674
TI - HSF1 and HSF3 cooperatively regulate the heat shock response in lizards.
AB - Cells cope with temperature elevations, which cause protein misfolding, by
expressing heat shock proteins (HSPs). This adaptive response is called the heat
shock response (HSR), and it is regulated mainly by heat shock transcription
factor (HSF). Among the four HSF family members in vertebrates, HSF1 is a master
regulator of HSP expression during proteotoxic stress including heat shock in
mammals, whereas HSF3 is required for the HSR in birds. To examine whether only
one of the HSF family members possesses the potential to induce the HSR in
vertebrate animals, we isolated cDNA clones encoding lizard and frog HSF genes.
The reconstructed phylogenetic tree of vertebrate HSFs demonstrated that HSF3 in
one species is unrelated with that in other species. We found that the DNA
binding activity of both HSF1 and HSF3 in lizard and frog cells was induced in
response to heat shock. Unexpectedly, overexpression of lizard and frog HSF3 as
well as HSF1 induced HSP70 expression in mouse cells during heat shock,
indicating that the two factors have the potential to induce the HSR.
Furthermore, knockdown of either HSF3 or HSF1 markedly reduced HSP70 induction in
lizard cells and resistance to heat shock. These results demonstrated that HSF1
and HSF3 cooperatively regulate the HSR at least in lizards, and suggest complex
mechanisms of the HSR in lizards as well as frogs.
PMID- 28686676
TI - Exotic QTL improve grain quality in the tri-parental wheat population SW84.
AB - DEVELOPING THE TRI-PARENTAL EXOTIC WHEAT POPULATION SW84: Genetic diversity of
cultivated wheat was markedly reduced, first, during domestication and, second,
since the onset of modern elite breeding. There is an increasing demand for
utilizing genetic resources to increase genetic diversity and, simultaneously, to
improve agronomic performance of cultivated wheat. To locate favorable effects of
exotic wheat alleles, we developed the tri-parental wheat population SW84. The
population was derived from crossing the hexaploid spring wheat cultivars Triso
and Devon with one synthetic exotic donor accession, Syn084L, followed by two
rounds of backcrossing and three rounds of selfing. SW84 consists of 359 BC2F4
lines, split into two families, D84 (Devon*Syn084L) and T84 (Triso*Syn084L).
STUDYING THE GENETIC CONTROL OF GRAIN QUALITY IN SW84: As a case study, grain
quality of SW84 was studied in replicated field trials. Transgressive segregation
was observed for all studied grain quality traits by evaluating SW84 for two
years at two locations under low and high nitrogen supply. Subsequently, a genome
wide association study (GWAS) was carried out based on genomic data derived from
a 90k Infinium iSELECT single nucleotide polymorphism (SNP) array. In total, GWAS
yielded 37 marker-trait associations, summarized to 16 quantitative trait loci
(QTL). These SNPs indicate genetic regulators of grain protein content, grain
hardness, sedimentation value and sedimentation ratio. The majority of exotic QTL
alleles (75%) exerted favorable effects, increasing grain protein content and
sedimentation value in ten and two cases, respectively. For instance, two exotic
QTL alleles were associated with a substantial increase of grain protein content
and sedimentation value by 1.09% and 7.31 ml, respectively. This finding confirms
the potential of exotic germplasm to improve grain quality in cultivated wheat.
So far, the molecular nature of most of the detected QTL is unknown. However, two
QTL correspond to known genes controlling grain quality: The major QTL on
chromosome 6B, increasing grain protein content by 0.70%, on average, co
localizes with the NAM-B1 gene, known to control grain protein content as well as
iron and zinc content. Likewise, the major QTL on chromosome 5D, reducing grain
hardness by 8.98%, on average, co-localizes with the gene for puroindoline b
(Pinb-D1) at the Ha locus. In total, 13 QTL were detected across families,
whereas one and three QTL were exclusively detected in families D84 and T84,
respectively. Likewise, ten QTL were detected across nitrogen treatments, whereas
one and five QTL were exclusively detected under low and high N treatments,
respectively. Our data indicate that most effects in SW84 act across families and
N levels. Merging of data from two families or two N treatments may, thus, be
considered in association studies to increase sample size and, as a result, QTL
detection power. UTILIZING FAVORABLE EXOTIC QTL ALLELES IN WHEAT BREEDING: Our
study serves as a model how favorable exotic QTL alleles can be located in exotic
germplasm of wheat. In future, the localized favorable exotic QTL alleles will be
utilized in wheat breeding programs to simultaneously improve grain quality and
selectively expand genetic diversity of the elite wheat gene pool.
PMID- 28686678
TI - Self-reported HIV-positive status but subsequent HIV-negative test result using
rapid diagnostic testing algorithms among seven sub-Saharan African military
populations.
AB - HIV rapid diagnostic tests (RDTs) combined in an algorithm are the current
standard for HIV diagnosis in many sub-Saharan African countries, and extensive
laboratory testing has confirmed HIV RDTs have excellent sensitivity and
specificity. However, false-positive RDT algorithm results have been reported due
to a variety of factors, such as suboptimal quality assurance procedures and
inaccurate interpretation of results. We conducted HIV serosurveys in seven sub
Saharan African military populations and recorded the frequency of personnel self
reporting HIV positivity, but subsequently testing HIV-negative during the
serosurvey. The frequency of individuals who reported they were HIV-positive but
subsequently tested HIV-negative using RDT algorithms ranged from 3.3 to 91.1%,
suggesting significant rates of prior false-positive HIV RDT algorithm results,
which should be confirmed using biological testing across time in future studies.
Simple measures could substantially reduce false-positive results, such as
greater adherence to quality assurance guidelines and prevalence-specific HIV
testing algorithms as described in the World Health Organization's HIV testing
guidelines. Other measures to improve RDT algorithm specificity include
classifying individuals with weakly positive test lines as HIV indeterminate and
retesting. While expansion of HIV testing in resource-limited countries is
critical to identifying HIV-infected individuals for appropriate care and
treatment, careful attention to potential causes of false HIV-positive results
are needed to prevent the significant medical, psychological, and fiscal costs
resulting from individuals receiving a false-positive HIV diagnosis.
PMID- 28686677
TI - MDR1A deficiency restrains tumor growth in murine colitis-associated
carcinogenesis.
AB - Patients with Ulcerative Colitis (UC) have an increased risk to develop colitis
associated colorectal cancer (CAC). Here, we found that protein expression of
ABCB1 (ATP Binding Cassette Subfamily B Member 1) / MDR1 (multidrug resistance 1)
was diminished in the intestinal mucosa of patients with active UC with or
without CAC, but not in non-UC patients with sporadic colon cancer. We
investigated the consequences of ABCB1/MDR1 loss-of-function in a common murine
model for CAC (AOM/DSS). Mice deficient in MDR1A (MDR1A KO) showed enhanced
intratumoral inflammation and cellular damage, which were associated with reduced
colonic tumor size and decreased degree of dysplasia, when compared to wild-type
(WT). Increased cell injury correlated with reduced capacity for growth of MDR1A
KO tumor spheroids cultured ex-vivo. Gene expression analysis by microarray
demonstrated that MDR1A deficiency shaped the inflammatory response towards an
anti-tumorigenic microenvironment by downregulating genes known to be important
mediators of cancer progression (PTGS2 (COX2), EREG, IL-11). MDR1A KO tumors
showed increased gene expression of TNFSF10 (TRAIL), a known inducer of cancer
cell death, and CCL12, a strong trigger of B cell chemotaxis. Abundant B220+ B
lymphocyte infiltrates with interspersed CD138+ plasma cells were recruited to
the MDR1A KO tumor microenvironment, concomitant with high levels of
immunoglobulin light chain genes. In contrast, MDR1A deficiency in RAG2 KO mice
that lack both B and T cells aggravated colonic tumor progression. MDR1A KO CD19+
B cells, but not WT CD19+ B cells, suppressed growth of colonic tumor-derived
spheroids from AOM/DSS-WT mice in an ex-vivo co-culture system, implying that B
cell regulated immune responses contributed to delayed tumor development in MDR1A
deficiency. In conclusion, we provide first evidence that loss of ABCB1/MDR1
function may represent an essential tumor-suppressive host defense mechanism in
CAC.
PMID- 28686679
TI - The acoustic repertoire and behavioural context of the vocalisations of a
nocturnal dasyurid, the eastern quoll (Dasyurus viverrinus).
AB - Defining an acoustic repertoire is essential to understanding vocal signalling
and communicative interactions within a species. Currently, quantitative and
statistical definition is lacking for the vocalisations of many dasyurids, an
important group of small to medium-sized marsupials from Australasia that
includes the eastern quoll (Dasyurus viverrinus), a species of conservation
concern. Beyond generating a better understanding of this species' social
interactions, determining an acoustic repertoire will further improve detection
rates and inference of vocalisations gathered by automated bioacoustic recorders.
Hence, this study investigated eastern quoll vocalisations using objective signal
processing techniques to quantitatively analyse spectrograms recorded from 15
different individuals. Recordings were collected in conjunction with observations
of the behaviours associated with each vocalisation to develop an acoustic-based
behavioural repertoire for the species. Analysis of recordings produced a
putative classification of five vocalisation types: Bark, Growl, Hiss, Cp-cp, and
Chuck. These were most frequently observed during agonistic encounters between
conspecifics, most likely as a graded sequence from Hisses occurring in a warning
context through to Growls and finally Barks being given prior to, or during,
physical confrontations between individuals. Quantitative and statistical methods
were used to objectively establish the accuracy of these five putative call
types. A multinomial logistic regression indicated a 97.27% correlation with the
perceptual classification, demonstrating support for the five different
vocalisation types. This putative classification was further supported by
hierarchical cluster analysis and silhouette information that determined the
optimal number of clusters to be five. Minor disparity between the objective and
perceptual classifications was potentially the result of gradation between
vocalisations, or subtle differences present within vocalisations not discernible
to the human ear. The implication of these different vocalisations and their
given context is discussed in relation to the ecology of the species and the
potential application of passive acoustic monitoring techniques.
PMID- 28686680
TI - Resveratrol ameliorates diet-induced dysregulation of lipid metabolism in
zebrafish (Danio rerio).
AB - Defective lipid metabolism is associated with increased risk of various chronic
diseases, such as obesity, cardiovascular diseases, and diabetes. Resveratrol
(RSV), a natural polyphenol, has been shown the potential of ameliorating
disregulations of lipid metabolism. The objective of this study was to
investigate the effects of feed intake and RSV on lipid metabolism in zebrafish
(Danio rerio). The adult males were randomly allocated to 6 groups: control (Con,
8 mg cysts/fish/day), control with 20 MUmol/L RSV (Con+RSV), calorie restriction
(CR, 5 mg cysts/fish/day), calorie restriction with RSV (CR+RSV), overfeed (OF,
60 mg cysts/fish/day), and overfeed with RSV (OF+RSV) groups. The treatment
period was 8 weeks. Results showed that CR reduced body length, body weight, and
condition factor of zebrafish. CR reduced levels of plasma triglyceride (TG) and
induced protein expression of phosphorylated AMP-activated protein kinase-alpha
(pAMPKalpha), silent information regulator 2 homolog 1 (Sirt1), and peroxisome
proliferator activated receptor gamma coactivator-1alpha (PGC1alpha). RSV
attenuated CR-induced pAMPKalpha/AMPKalphaincreases. RSV increased levels of
Sirt1 protein in the OF zebrafish, and decreased OF-induced increase in
peroxisome proliferator-activated receptor-gamma (PPARgamma) protein level.
Additionally, RSV down-regulated caveolin-1 and up-regulated microtubule
associated protein 1 light chain 3 -II (LC3-II) protein levels in OF zebrafish.
In conclusion, these results suggest that 1) CR reduces plasma TG level through
activation of the AMPKalpha-Sirt1- PGC1alpha pathway; 2) under different dietary
stress conditions RSV might regulate AMPK phosphorylation bi-directionally; 3)
RSV might regulate lipid metabolism through the AMPKalpha-Sirt1-PPARgamma pathway
in OF zebrafish.
PMID- 28686682
TI - A road damage and life-cycle greenhouse gas comparison of trucking and pipeline
water delivery systems for hydraulically fractured oil and gas field development
in Colorado.
AB - The process of hydraulic fracturing for recovery of oil and natural gas uses
large amounts of fresh water and produces a comparable amount of wastewater, much
of which is typically transported by truck. Truck transport of water is an
expensive and energy-intensive process with significant external costs including
roads damages, and pollution. The integrated development plan (IDP) is the
industry nomenclature for an integrated oil and gas infrastructure system
incorporating pipeline-based transport of water and wastewater, centralized water
treatment, and high rates of wastewater recycling. These IDP have been proposed
as an alternative to truck transport systems so as to mitigate many of the
economic and environmental problems associated with natural gas production, but
the economic and environmental performance of these systems have not been
analyzed to date. This study presents a quantification of lifecycle greenhouse
gas (GHG) emissions and road damages of a generic oil and gas field, and of an
oil and gas development sited in the Denver-Julesburg basin in the northern
Colorado region of the US. Results demonstrate that a reduction in economic and
environmental externalities can be derived from the development of these IDP
based pipeline water transportation systems. IDPs have marginal utility in
reducing GHG emissions and road damage when they are used to replace in-field
water transport, but can reduce GHG emissions and road damage by factors of as
much as 6 and 7 respectively, when used to replace fresh water transport and
waste-disposal routes for exemplar Northern Colorado oil and gas fields.
PMID- 28686681
TI - KIR and their HLA Class I ligands: Two more pieces towards completing the puzzle
of chronic rejection and graft loss in kidney transplantation.
AB - BACKGROUND: Kidney transplantation is a life-saving treatment for patients with
end-stage renal disease. However, despite progress in surgical techniques and
patient management, immunological rejection continues to have a negative impact
on graft function and overall survival. Incompatibility between donors and
recipients for human leukocyte antigens (HLA) of the major histocompatibility
complex (MHC) generates a series of complex cellular and humoral immune response
mechanisms that are largely responsible for rejection and loss of graft function.
Within this context, a growing amount of evidence shows that alloreactive natural
killer (NK) cells play a critical role in the immune response mechanisms elicited
by the allograft. Killer immunoglobulin-like receptors (KIRs) are prominent
mediators of NK cell alloreactivity. METHODS AND FINDINGS: A cohort of 174 first
cadaveric kidney allograft recipients and their donors were selected from a total
cohort of 657 transplanted patients for retrospective immunogenetic analyses.
Patients with HLA Class II mismatches were excluded. HLA Class I allele
frequencies were compared among patients with chronic rejection, patients with
stable graft function and a group of 2388 healthy controls. Activating and
inhibitory KIR gene frequencies, KIR haplotypes, KIR-HLA ligand
matches/mismatches and combinations of recipient KIRs and donor HLA Class I
ligands were compared among patients with and without chronic rejection and a
group of 221 healthy controls. Patients transplanted from donors homozygous for
HLA-C1 antigens had a significantly higher risk for chronic rejection than
patients transplanted from donors homozygous or heterozygous for HLA-C2 antigens
or with epitopes belonging to the HLA-Bw4 ligand group. The Kaplan-Meier curves
obtained by dividing the patients into 3 groups according to the presence or
absence of one or both of the combinations of recipient KIRs and donor HLA
ligands (rKIR2DL1/dHLA-C2 and rKIR3DL1/dHLA-Bw4) showed a significantly higher
cumulative incidence of chronic rejection in the group of patients completely
lacking these functional units. These patients showed a progressively stronger
decline in modification of diet in renal disease-estimated glomerular filtration
rate. CONCLUSIONS: KIR genotyping should be performed at the time of enrolment of
patients on the waiting list for organ transplantation. In our study, a
significantly higher risk of chronic rejection after kidney transplantation was
observed when recipient (r) and donor (d) pairs completely lacked the two
functional rKIR-dHLA ligand combinations rKIR2DL1/dHLA-C2 and rKIR3DL1/dHLA-Bw4.
This immunogenetic profile corresponds to low levels of NK cell inhibition.
Therefore, patients with this high risk profile could benefit from
immunosuppressive therapy aimed at reducing NK-cell cytotoxicity.
PMID- 28686684
TI - Correction: Heart rate variability during hemodialysis is an indicator for long
term vascular access survival in uremic patients.
AB - [This corrects the article DOI: 10.1371/journal.pone.0172212.].
PMID- 28686683
TI - Immunohistochemical identification of Propionibacterium acnes in granuloma and
inflammatory cells of myocardial tissues obtained from cardiac sarcoidosis
patients.
AB - BACKGROUND: Although rare, cardiac sarcoidosis (CS) is potentially fatal. Early
diagnosis and intervention are essential, but histopathologic diagnosis is
limited. We aimed to detect Propionibacterium acnes, a commonly implicated
etiologic agent of sarcoidosis, in myocardial tissues obtained from CS patients.
METHODS AND RESULTS: We examined formalin-fixed paraffin-embedded myocardial
tissues obtained by surgery or autopsy and endomyocardial biopsy from patients
with CS (n = 26; CS-group), myocarditis (n = 15; M-group), or other
cardiomyopathies (n = 39; CM-group) using immunohistochemistry (IHC) with a P.
acnes-specific monoclonal antibody. We found granulomas in 16 (62%) CS-group
samples. Massive (>=14 inflammatory cells) and minimal (<14 inflammatory cells)
inflammatory foci, respectively, were detected in 16 (62%) and 11 (42%) of the CS
group samples, 10 (67%) and 10 (67%) of the M-group samples, and 1 (3%) and 18
(46%) of the CM-group samples. P. acnes-positive reactivity in granulomas,
massive inflammatory foci, and minimal inflammatory foci were detected in 10
(63%), 10 (63%), and 8 (73%) of the CS-group samples, respectively, and in none
of the M-group and CM-group samples. CONCLUSIONS: Frequent identification of P.
acnes in sarcoid granulomas of originally aseptic myocardial tissues suggests
that this indigenous bacterium causes granuloma in many CS patients. IHC
detection of P. acnes in massive or minimal inflammatory foci of myocardial
biopsy samples without granulomas may be useful for differentiating sarcoidosis
from myocarditis or other cardiomyopathies.
PMID- 28686685
TI - Comparative proteomic analysis of Gib2 validating its adaptor function in
Cryptococcus neoformans.
AB - Cryptococcus neoformans causes often-fatal fungal meningoencephalitis in
immunocompromised individuals. While the exact disease mechanisms remain elusive,
signal transduction pathways mediated by key elements such as G-protein alpha
subunit Gpa1, small GTPase Ras1, and atypical Gbeta-like/RACK1 protein Gib2 are
known to play important roles in C. neoformans virulence. Gib2 is important for
normal growth, differentiation, and pathogenicity, and it also positively
regulates cAMP levels in conjunction with Gpa1. Interestingly, Gib2 displays a
scaffold protein property by interacting with a wide variety of cellular
proteins. To explore Gib2 global regulatory functions, we performed two
dimensional differential gel electrophoresis (DIGE) analysis and found that GIB2
disruption results in an increased expression of 304 protein spots (43.4%) and a
decreased expression of 396 protein spots (56.6%). Analysis of 96 proteins whose
expression changes were deemed significant (>= +/- 1.5- fold) revealed that 75
proteins belong to at least 12 functional protein groups. Among them, eight
groups have the statistical stringency of p <= 0.05, and four groups, including
Hsp70/71 heat shock protein homologs and ribosomal proteins, survived the
Bonferroni correction. This finding is consistent with earlier established roles
for the human Gbeta-like/RACK1 and the budding yeast Saccharomyces cerevisiae
Asc1. It suggests that Gib2 could also be part of the complex affecting ribosomal
biogenesis and protein translation in C. neoformans. Since eukaryotic Hsp70/71
proteins are involved in the facilitation of nascent protein folding, processing,
and protection of cells against stress, we also propose that Gib2-regulated
stress responses are linked to fungal virulence. Collectively, our study supports
a conserved role of Gbeta-like/RACK/Gib2 proteins in the essential cellular
process of ribosomal biogenesis and protein translation. Our study also
highlights a multifaceted regulatory role of Gib2 in the growth and pathogenicity
of C. neoformans.
PMID- 28686686
TI - Protective effect of zinc preconditioning against renal ischemia reperfusion
injury is dose dependent.
AB - OBJECTIVES: Ischemia-reperfusion injury (IRI) is a major cause of acute kidney
injury and chronic kidney disease. Two promising preconditioning methods for the
kidney, intermittent arterial clamping (IC) and treatment with the hypoxia
mimetic cobalt chloride, have never been directly compared. Furthermore, the
protective efficacy of the chemically related transition metal Zn2+ against renal
IRI is unclear. Although Co2+ ions have been shown to protect the kidney via
hypoxia inducible factor (HIF), the effect of Zn2+ ions on the induction of
HIF1alpha, HIF2alpha and HIF3alpha has not been investigated previously.
MATERIALS AND METHODS: The efficacy of different preconditioning techniques was
assessed using a Sprague-Dawley rat model of renal IRI. Induction of HIF proteins
following Zn2+ treatment of the human kidney cell lines HK-2 (immortalized normal
tubular cells) and ACHN (renal cancer) was measured using Western Blot. RESULTS:
Following 40 minutes of renal ischemia in rats, cobalt preconditioning offered
greater protection against renal IRI than IC as evidenced by lower peak serum
creatinine and urea concentrations. ZnCl2 (10 mg/kg) significantly lowered the
creatinine and urea concentrations compared to saline-treated control rats
following a clinically relevant 60 minutes of ischemia. Zn2+ induced expression
of HIF1alpha and HIF2alpha but not HIF3alpha in HK-2 and ACHN cells. CONCLUSION:
ZnCl2 preconditioning protects against renal IRI in a dose-dependent manner.
Further studies are warranted to determine the possible mechanisms involved, and
to assess the benefit of ZnCl2 preconditioning for clinical applications.
PMID- 28686687
TI - Characterizing roots and water uptake in a ground cover rice production system.
AB - BACKGROUND AND AIMS: Water-saving ground cover rice production systems (GCRPS)
are gaining popularity in many parts of the world. We aimed to describe the
characteristics of root growth, morphology, distribution, and water uptake for a
GCRPS. METHODS: A traditional paddy rice production system (TPRPS) was compared
with GCRPS in greenhouse and field experiments. In the greenhouse, GCRPS where
root zone average soil water content was kept near saturation (GCRPSsat), field
capacity (GCRPSfwc) and 80% field capacity (GCRPS80%), were evaluated. In a two
year field experiment, GCRPSsat and GCRPS80% were applied. RESULTS: Similar
results were found in greenhouse and field experiments. Before mid-tillering the
upper soil temperature was higher for GCRPS, leading to enhanced root dry weight,
length, surface area, specific root length, and smaller diameter of roots but
lower water uptake rate per root length compared to TPRPS. In subsequent growth
stages, the reduced soil water content under GCRPS caused that the preponderance
of root growth under GCRPSsat disappeared in comparison to TPRPS. Under other
GCRPS treatments (GCRPSfwc and GCRPS80%), significant limitation on root growth,
bigger root diameter and higher water uptake rate per root length were found.
CONCLUSIONS: Discrepancies in soil water and temperature between TPRPS and GCRPS
caused adjustments to root growth, morphology, distribution and function. Even
though drought stress was inevitable after mid-tillering under GCRPS, especially
GCRPS80%, similar or even enhanced root water uptake capacity in comparison to
TPRPS might promote allocation of photosynthetic products to shoots and increase
water productivity.
PMID- 28686688
TI - Therapeutic impact of dietary vitamin D supplementation for preventing right
ventricular remodeling and improving survival in pulmonary hypertension.
AB - BACKGROUND: Pulmonary hypertension (PH), caused by elevated pulmonary vascular
resistance, leads to right heart failure and ultimately death. Vitamin D
deficiency can predispose individuals to hypertension and left ventricular
dysfunction; however, it remains unknown how serum vitamin D level is related to
PH and right ventricular (RV) dysfunction. METHODS: Serum 25-hydroxyvitamin D
[25(OH)D] levels were assessed in PH patients for an association with disease
severity. To examine whether vitamin D supplementation could prevent the
development of pulmonary vascular remodeling and RV dysfunction in PH, a rat
model of PH was fed either normal chow or a high vitamin D diet. RESULTS: The
majority (95.1%) of PH patients had 25(OH)D levels in the insufficiency range,
which is associated with increased mean pulmonary artery pressure, increased
pulmonary vascular resistance, and decreased cardiac output in PH patients.
Vitamin D supplementation significantly increased serum 25(OH)D levels and
improved survival in PH rats. Interestingly, while the supplemented rats retained
the typical increases in medial thickness of the muscular pulmonary arteries and
RV systolic pressure, RV cardiomyocyte hypertrophy and B-type natriuretic peptide
expression was significantly attenuated. CONCLUSIONS: Vitamin D deficiency is
frequently seen in patients diagnosed with PH and low serum levels of 25(OH)D are
associated with severity of PH and RV dysfunction. Vitamin D supplementation in
PH rats improved survival via ameliorating pathological RV hypertrophy. These
findings suggest an insufficient intake of vitamin D might potentially accelerate
RV dysfunction, leading to a crucial clinical impact of vitamin D supplementation
in PH.
PMID- 28686689
TI - Correction: Prevalence and extent of heteroresistance by next generation
sequencing of multidrug-resistant tuberculosis.
AB - [This corrects the article DOI: 10.1371/journal.pone.0176522.].
PMID- 28686690
TI - Shifts in the bacterial community composition along deep soil profiles in
monospecific and mixed stands of Eucalyptus grandis and Acacia mangium.
AB - Our knowledge of the rhizosphere bacterial communities in deep soils and the role
of Eucalyptus and Acacia on the structure of these communities remains very
limited. In this study, we targeted the bacterial community along a depth profile
(0 to 800 cm) and compared community structure in monospecific or mixed
plantations of Acacia mangium and Eucalyptus grandis. We applied quantitative PCR
(qPCR) and sequence the V6 region of the 16S rRNA gene to characterize
composition of bacterial communities. We identified a decrease in bacterial
abundance with soil depth, and differences in community patterns between
monospecific and mixed cultivations. Sequence analysis indicated a prevalent
effect of soil depth on bacterial communities in the mixed plant cultivation
system, and a remarkable differentiation of bacterial communities in areas solely
cultivated with Eucalyptus. The groups most influenced by soil depth were
Proteobacteria and Acidobacteria (more frequent in samples between 0 and 300 cm).
The predominant bacterial groups differentially displayed in the monospecific
stands of Eucalyptus were Firmicutes and Proteobacteria. Our results suggest that
the addition of an N2-fixing tree in a monospecific cultivation system modulates
bacterial community composition even at a great depth. We conclude that co
cultivation systems may represent a key strategy to improve soil resources and to
establish more sustainable cultivation of Eucalyptus in Brazil.
PMID- 28686691
TI - Use of fecal volatile organic compound analysis to discriminate between non
vaccinated and BCG-Vaccinated cattle prior to and after Mycobacterium bovis
challenge.
AB - Bovine tuberculosis is a zoonotic disease of global public health concern.
Development of diagnostic tools to improve test accuracy and efficiency in
domestic livestock and enable surveillance of wildlife reservoirs would improve
disease management and eradication efforts. Use of volatile organic compound
analysis in breath and fecal samples is being developed and optimized as a means
to detect disease in humans and animals. In this study we demonstrate that VOCs
present in fecal samples can be used to discriminate between non-vaccinated and
BCG-vaccinated cattle prior to and after Mycobacterium bovis challenge.
PMID- 28686692
TI - Estimating influenza and respiratory syncytial virus-associated mortality in
Western Kenya using health and demographic surveillance system data, 2007-2013.
AB - BACKGROUND: Influenza and respiratory syncytial virus (RSV) associated mortality
has not been well-established in tropical Africa. METHODS: We used the negative
binomial regression method and the rate-difference method (i.e. deaths during low
and high influenza/RSV activity months), to estimate excess mortality
attributable to influenza and RSV using verbal autopsy data collected through a
health and demographic surveillance system in Western Kenya, 2007-2013. Excess
mortality rates were calculated for a) all-cause mortality, b) respiratory deaths
(including pneumonia), c) HIV-related deaths, and d) pulmonary tuberculosis (TB)
related deaths. RESULTS: Using the negative binomial regression method, the mean
annual all-cause excess mortality rate associated with influenza and RSV was 14.1
(95% confidence interval [CI] 0.0-93.3) and 17.1 (95% CI 0.0-111.5) per 100,000
person-years (PY) respectively; and 10.5 (95% CI 0.0-28.5) and 7.3 (95% CI 0.0
27.3) per 100,000 PY for respiratory deaths, respectively. Highest mortality
rates associated with influenza were among >=50 years, particularly among persons
with TB (41.6[95% CI 0.0-122.7]); and with RSV were among <5 years. Using the
rate-difference method, the excess mortality rate for influenza and RSV was 44.8
(95% CI 36.8-54.4) and 19.7 (95% CI 14.7-26.5) per 100,000 PY, respectively, for
all-cause deaths; and 9.6 (95% CI 6.3-14.7) and 6.6 (95% CI 3.9-11.0) per 100,000
PY, respectively, for respiratory deaths. CONCLUSIONS: Our study shows a
substantial excess mortality associated with influenza and RSV in Western Kenya,
especially among children <5 years and older persons with TB, supporting
recommendations for influenza vaccination and efforts to develop RSV vaccines.
PMID- 28686693
TI - Ivermectin treatment of Loa loa hyper-microfilaraemic baboons (Papio anubis):
Assessment of microfilarial load reduction, haematological and biochemical
parameters and histopathological changes following treatment.
AB - BACKGROUND: Individuals with high intensity of Loa loa are at risk of developing
serious adverse events (SAEs) post treatment with ivermectin. These SAEs have
remained unclear and a programmatic impediment to the advancement of community
directed treatment with ivermectin. The pathogenesis of these SAEs following
ivermectin has never been investigated experimentally. The Loa/baboon (Papio
anubis) model can be used to investigate the pathogenesis of Loa-associated
encephalopathy following ivermectin treatment in humans. METHODS: 12 baboons with
microfilarial loads > 8,000mf/mL of blood were randomised into four groups: Group
1 (control group receiving no drug), Group 2 receiving ivermectin (IVM) alone,
Group 3 receiving ivermectin plus aspirin (IVM + ASA), and Group 4 receiving
ivermectin plus prednisone (IVM + PSE). Blood samples collected before treatment
and at Day 5, 7 or 10 post treatment, were analysed for parasitological,
hematological and biochemical parameters using standard techniques. Clinical
monitoring of animals for side effects took place every 6 hours post treatment
until autopsy. At autopsy free fluids and a large number of standard organs were
collected, examined and tissues fixed in 10% buffered formalin and processed for
standard haematoxylin-eosin staining and specific immunocytochemical staining.
RESULTS: Mf counts dropped significantly (p<0.05) in all animals following
ivermectin treatment with reductions as high as (89.9%) recorded; while no
significant drop was observed in the control animals. Apart from haemoglobin (Hb)
levels which recorded a significant (p = 0.028) drop post treatment, all other
haematological and biochemical parameters did not show any significant changes
(p>0.05). All animals became withdrawn 48 hours after IVM administration. All
treated animals recorded clinical manifestations including rashes, itching,
diarrhoea, conjunctival haemorrhages, lymph node enlargement, pinkish ears,
swollen face and restlessness; one animal died 5 hours after IVM administration.
Macroscopic changes in post-mortem tissues observed comprised haemorrhages in the
brain, lungs, heart, which seen in all groups given ivermectin but not in the
untreated animals. Microscopically, the major cellular changes seen, which were
present in all the ivermectin treated animals included microfilariae in varying
degrees of degeneration in small vessels. These were frequently associated with
fibrin deposition, endothelial changes including damage to the integrity of the
blood vessel and the presence of extravascular erythrocytes (haemorrhages). There
was an increased presence of eosinophils and other chronic inflammatory types in
certain tissues and organs, often in large numbers and associated with
microfilarial destruction. Highly vascularized organs like the brain, heart,
lungs and kidneys were observed to have more microfilariae in tissue sections.
The number of mf seen in the brain and kidneys of animals administered IVM alone
tripled that of control animals. Co-administration of IVM + PSE caused a greater
increase in mf in the brain and kidneys while the reverse was noticed with the co
administration of IVM + ASA. CONCLUSIONS: The treatment of Loa hyper
microfilaraemic individuals with ivermectin produces a clinical spectrum that
parallels that seen in Loa hyper-microfilaraemic humans treated with ivermectin.
The utilization of this experimental model can contribute to the improved
management of the adverse responses in humans.
PMID- 28686694
TI - Genetic structure provides insights into the geographic origins and temporal
change in the invasive charru mussel (Sururu) in the southeastern United States.
AB - In 2004, Mytella charruana (d'Orbigny, 1842) (Mollusca: Bivalvia: Mytilidae)
became established along the coast of the southeastern United States (SE-US).
Using mitochondrial DNA sequencing (cytochrome c oxidase subunit I), we compared
genetic variation throughout its native range in South America to its invasive
range in the SE-US. Samples from the SE-US were collected in 2006 and 2010
enabling a temporal comparison to evaluate possible genetic changes of the
invasive population. We addressed two questions. First, what are the potential
source populations (or geographic regions) for the SE-US invasion? Second, how
has genetic diversity changed between the two sampling periods within the SE-US?
We identified a total of 72 haplotypes, 64 of which were isolated to geographic
sites and only 8 were shared among sites. The highly structured native range
provides insight into the origin of invasive populations where our results
suggest that the introduced SE-US population originated from multiple source
populations with the Panama region as the primary source. Additionally, our
results indicate that genetic composition of the non-native populations was
unchanged between the two sampling periods. Mytella charruana exhibit a
significant pattern of genetic structure among natural populations, owing to
biogeographic barriers that limit natural dispersal, and an ability to persist in
novel habitats, owing to a suite of life-history characters that favor survival
under variable conditions. Overall, this study explains why M. charruana may
become an increasing threat to locations founded by anthropogenic transportation.
PMID- 28686695
TI - Coronary artery disease-associated genetic variants and biomarkers of
inflammation.
AB - INTRODUCTION: Genetic constitution and inflammation both contribute to
development of coronary artery disease (CAD). Several CAD-associated single
nucleotide polymorphisms (SNPs) have recently been identified, but their
functions are largely unknown. We investigated the associations between CAD
associated SNPs and five CAD-related inflammatory biomarkers. METHODS: We
genotyped 45 CAD-associated SNPs in 701 stable CAD patients in whom levels of
high-sensitivity C-reactive protein (hsRCP), interleukin-6, calprotectin,
fibrinogen and complement component 3 levels had previously been measured. A
genetic risk score was calculated to assess the combined risk associated with all
the genetic variants. A multiple linear regression model was used to assess
associations between the genetic risk score, single SNPs, and the five
inflammatory biomarkers. RESULTS: The minor allele (G) (CAD risk allele) of
rs2075650 (TOMM40/APOE) was associated with lower levels of high-sensitivity C
reactive protein (effect per risk allele: -0.37 mg/l [95%CI -0.56 to -0.18
mg/l]). The inflammatory markers tested showed no association with the remaining
44 SNPs or with the genetic risk score. CONCLUSIONS: In stable CAD patients, the
risk allele of a common CAD-associated marker at the TOMM40/APOE locus was
associated with lower hsCRP levels. No other genetic variants or the combined
effect of all variants were associated with the five inflammatory biomarkers.
PMID- 28686696
TI - Morphological and transcriptomic evidence for ammonium induction of sexual
reproduction in Thalassiosira pseudonana and other centric diatoms.
AB - The reproductive strategy of diatoms includes asexual and sexual phases, but in
many species, including the model centric diatom Thalassiosira pseudonana, sexual
reproduction has never been observed. Furthermore, the environmental factors that
trigger sexual reproduction in diatoms are not understood. Although genome
sequences of a few diatoms are available, little is known about the molecular
basis for sexual reproduction. Here we show that ammonium reliably induces the
key sexual morphologies, including oogonia, auxospores, and spermatogonia, in two
strains of T. pseudonana, T. weissflogii, and Cyclotella cryptica. RNA sequencing
revealed 1,274 genes whose expression patterns changed when T. pseudonana was
induced into sexual reproduction by ammonium. Some of the induced genes are
linked to meiosis or encode flagellar structures of heterokont and cryptophyte
algae. The identification of ammonium as an environmental trigger suggests an
unexpected link between diatom bloom dynamics and strategies for enhancing
population genetic diversity.
PMID- 28686697
TI - Prognostic score in patients with recurrent or metastatic carcinoma of the head
and neck treated with cetuximab and chemotherapy.
AB - Despite modern treatment approaches, survival of patients with recurrent or
metastatic squamous cell carcinoma of the head and neck (SCCHN) remains low and
it is difficult to identify patients who derive optimal benefit from treatment.
We therefore analyzed which commonly available laboratory and clinical parameters
may help improve the prognostication in this patient group. This retrospective
monocenter analysis includes 128 patients with recurrent or metastatic SCCHN
treated with cetuximab alone or in combination with polychemotherapy as first
line therapy. Factors with independent prognostic power in the multivariate
analysis were used to build up a score separating patient groups with different
survival. Patients had a median age of 61 years and 103 patients were treated
with polychemotherapy plus cetuximab. An ECOG score above 1, high CRP and
leukocyte levels, less intensive treatment and a time below 12 months from
primary diagnosis to relapse remained as independent negative prognostic factors
in multivariate analysis. Patients with 0 to 1 risk factors had a median OS of
13.6 months compared to a median OS of less than one month for patients 4 to 5
risk factors (p<0.001). This study identifies 5 clinical and serum values that
influence survival of patients with recurrent or metastatic SCCHN treated with
cetuximab. By combining these factors to create a score for OS, it is possible to
distinguish a group of patients with significantly improved survival and define
those most likely to have no benefit from cetuximab treatment.
PMID- 28686699
TI - Correction: Urinary iodine concentration (UIC) could be a promising biomarker for
predicting goiter among school-age children: A systematic review and meta
analysis.
AB - [This corrects the article DOI: 10.1371/journal.pone.0174095.].
PMID- 28686698
TI - Flow velocity-driven differentiation of human mesenchymal stromal cells in silk
fibroin scaffolds: A combined experimental and computational approach.
AB - Mechanical loading plays a major role in bone remodeling and fracture healing.
Mimicking the concept of mechanical loading of bone has been widely studied in
bone tissue engineering by perfusion cultures. Nevertheless, there is still
debate regarding the in-vitro mechanical stimulation regime. This study aims at
investigating the effect of two different flow rates (vlow = 0.001m/s and vhigh =
0.061m/s) on the growth of mineralized tissue produced by human mesenchymal
stromal cells cultured on 3-D silk fibroin scaffolds. The flow rates applied were
chosen to mimic the mechanical environment during early fracture healing or
during bone remodeling, respectively. Scaffolds cultured under static conditions
served as a control. Time-lapsed micro-computed tomography showed that
mineralized extracellular matrix formation was completely inhibited at vlow
compared to vhigh and the static group. Biochemical assays and histology
confirmed these results and showed enhanced osteogenic differentiation at vhigh
whereas the amount of DNA was increased at vlow. The biological response at vlow
might correspond to the early stage of fracture healing, where cell proliferation
and matrix production is prominent. Visual mapping of shear stresses, simulated
by computational fluid dynamics, to 3-D micro-computed tomography data revealed
that shear stresses up to 0.39mPa induced a higher DNA amount and shear stresses
between 0.55mPa and 24mPa induced osteogenic differentiation. This study
demonstrates the feasibility to drive cell behavior of human mesenchymal stromal
cells by the flow velocity applied in agreement with mechanical loading mimicking
early fracture healing (vlow) or bone remodeling (vhigh). These results can be
used in the future to tightly control the behavior of human mesenchymal stromal
cells towards proliferation or differentiation. Additionally, the combination of
experiment and simulation presented is a strong tool to link biological responses
to mechanical stimulation and can be applied to various in-vitro cultures to
improve the understanding of the cause-effect relationship of mechanical loading.
PMID- 28686700
TI - Rates of return to sorghum and millet research investments: A meta-analysis.
AB - Sorghum and millet grow in some of the most heterogeneous and austere
agroecologies around the world. These crops are amongst the top five cereal
sources of food and feed. Yet, few studies document the impact of sorghum and
millet genetic enhancement. The Internal Rate of Return (ROR) is one of the most
popular metrics used to measure the economic return on investment on agricultural
research and development (R&D). This study conducted a meta-analysis of 59
sorghum and millet ROR estimates obtained from 25 sources published between 1958
and 2015. The average rate of return to sorghum and millet R&D investment is
between 54-76 percent per year. All studies computed social rather than private
RORs because the technologies were developed using public funds originating from
host country National Agricultural Research Systems (NARS) and international
organizations such as the INTSORMIL CRSP, ICRISAT and others. Nearly three
quarter of the studies focused only on sorghum (72 percent) and around one tenth
of the studies (8 percent) on millet. Regression models analyzed the determinants
of variation in the reported RORs. Results show that ex-ante type and self
evaluated type of analyses are positively and significantly associated with the
ROR estimates. Compared to estimates conducted by a university, results from
international institutions and other mixed organizations provided significantly
smaller estimates. Estimates conducted at national level also are significantly
lower than those conducted at sub-national levels. The ROR is higher for studies
conducted in the United States and for those conducted more recently. The study
also reconstructed modified internal rate of return (MIRR) for a sub-sample of
the reported RORs following recent methods from the literature. These results
show that the MIRR estimates are significantly smaller than the reported ROR
estimates. Both results indicate that investment in sorghum and millet research
generates high social rates of return.
PMID- 28686701
TI - Correction: Aged dissolved organic carbon exported from rivers of the Tibetan
Plateau.
AB - [This corrects the article DOI: 10.1371/journal.pone.0178166.].
PMID- 28686703
TI - Correction: The "new normal": Adapting doctoral trainee career preparation for
broad career paths in science.
AB - [This corrects the article DOI: 10.1371/journal.pone.0177035.].
PMID- 28686702
TI - What is the level of evidence for the amnestic effects of sedatives in pediatric
patients? A systematic review and meta-analyses.
AB - BACKGROUND: Studies have suggested that benzodiazepines are amnestic drug par
excellence, but when taken together, what level of evidence do they generate? Are
other sedatives as amnestic as benzodiazepines? The aim of this study was to
assess the level of scientific evidence for the amnestic effect of sedatives in
pediatric patients who undergo health procedures. METHODS: The literature was
searched to identify randomized controlled trials that evaluated anterograde and
retrograde amnesia in 1-19-year-olds who received sedative drugs during health
procedures. Electronic databases, including PubMed, Scopus and Cochrane Library
besides clinical trial registries and grey literature were searched. Two
independent reviewers performed data extraction and risk of bias assessment using
the Cochrane Collaboration's Tool. The meta-analyses were performed by
calculating relative risk (RR) to 95% confidence intervals (CI). The quality of
the evidence was assessed using Grading of Recommendations Assessment,
Development and Evaluation approach. RESULTS: Fifty-four studies were included
(4,168 participants). A higher occurrence of anterograde amnesia was observed
when benzodiazepines, the most well-studied sedatives (n = 47), were used than
when placebo was used (n = 12) (RR = 3.10; 95% CI: 2.30-4.19, P<0.001; I2 = 14%),
with a moderate level of evidence. Higher doses of alpha2-adrenergic agonists
(clonidine/dexmedetomidine) produced more anterograde amnesia than lower doses (n
= 2) (RR = 1.83; 95% CI: 1.03-3.25; P = 0.038; I2 = 0%), with a low level of
evidence; benzodiazepines' amnestic effects were not dose-dependent (n = 3) (RR =
1.54; 95% CI: 0.96-2.49; P = 0.07; I2 = 12%) but the evidence was low. A
qualitative analysis showed that retrograde amnesia did not occur in 8 out of 10
studies. CONCLUSIONS: In children, moderate evidence support that benzodiazepines
induce anterograde amnesia, whereas the evidence for other sedatives is weak and
based on isolated and small studies. Further clinical trials focused on the
amnesia associated with non-benzodiazepine sedatives are therefore needed. TRIAL
REGISTRATION: PROSPERO CRD42015017559.
PMID- 28686704
TI - Chemosensitizing indomethacin-conjugated dextran-based micelles for effective
delivery of paclitaxel in resistant breast cancer therapy.
AB - Multidrug resistance (MDR) against chemotherapeutic agents has become the major
obstacle to successful cancer therapy and multidrug resistance-associated
proteins (MRPs) mediated drug efflux is the key factor for MDR. Indomethacin
(IND), one of the non-steroidal anti-inflammatory agents, has been demonstrated
to increase cytotoxic effects of anti-tumor agents as MRP substrates. In this
study, dextran-g-indomethacin (DEX-IND) polymeric micelles were designed to
delivery paclitaxel (PTX) for the treatment of MDR tumors. The DEX-IND polymer
could effectively encapsulate PTX with high loading content and DEX-IND/PTX
micelles present a small size distribution. Compared with free PTX, the release
of PTX from DEX-IND/PTX micelles could be prolonged to 48 h. Cellular uptake test
showed that the internalization of DEX-IND/PTX micelles by drug-sensitive MCF
7/ADR cells was significantly higher than free PTX benefiting from the inhibitory
effect of IND on MRPs. In vitro cytotoxicity test further demonstrated that DEX
IND/PTX micelles could enhance the cytotoxicity of PTX against MCF-7/ADR tumor
cells. In vivo pharmacokinetic results showed that DEX-IND/PTX micelles had
longer systemic circulation time and slower plasma elimination rate in comparison
to PTX. The anti-tumor efficacy test showed that DEX-IND/PTX micelles exhibited
greater tumor growth-inhibition effects on MDR tumor-bearing mice, with good
correlation between in vitro and in vivo. Overall, the cumulative evidence
indicates that DEX-IND/PTX micelles hold significant promise for the treatment of
MDR tumors.
PMID- 28686705
TI - Sputum quality and diagnostic performance of GeneXpert MTB/RIF among smear
negative adults with presumed tuberculosis in Uganda.
AB - BACKGROUND: Introduction of GeneXpert MTB/RIF (Xpert) assay has constituted a
major breakthrough for tuberculosis (TB) diagnostics. Several patient factors may
influence diagnostic performance of Xpert including sputum quality. OBJECTIVE: We
carried out a prospective, observational, cross-sectional study to determine the
effect of sputum quality on diagnostic performance of Xpert among presumed TB
patients in Uganda. METHODS: We collected clinical and demographic information
and two sputum samples from participants. Staff recorded sputum quality and
performed LED fluorescence microscopy and mycobacterial culture on each sample.
If both smear examinations were negative, Xpert testing was performed. We
calculated diagnostic yield, sensitivity, specificity, and other indicators for
Xpert for each stratum of sputum quality in reference to a standard of
mycobacterial culture. RESULTS: Patients with salivary sputum showed a trend
towards a substantially higher proportion of samples that were Xpert-positive
(54/286, 19%, 95% CI 15-24) compared with those with all other sputum sample
types (221/1496, 15%, 95% CI 13-17). Blood-stained sputum produced the lowest
sensitivity (28%; 95% CI 12-49) and salivary sputum the highest (66%; 95% CI 53
77). Specificity didn't vary meaningfully by sample types. Salivary sputum was
significantly more sensitive than mucoid sputum (+13%, 95% CI +1 to +26), while
blood-stained sputum was significantly less sensitive (-24%, 95% CI -42 to -5).
CONCLUSIONS: Our findings demonstrate the need to exercise caution in collecting
sputum for Xpert and in interpreting results because sputum quality may impact
test yield and sensitivity. In particular, it may be wise to pursue additional
testing should blood-stained sputum test negative while salivary sputum should be
readily accepted for Xpert testing given its higher sensitivity and potentially
higher yield than other sample types. These findings challenge conventional
recommendations against collecting salivary sputum for TB diagnosis and could
inform new standards for sputum quality.
PMID- 28686706
TI - Plasminogen Tochigi mice exhibit phenotypes similar to wild-type mice under
experimental thrombotic conditions.
AB - Plasminogen (Plg) is a precursor of plasmin that degrades fibrin. A race-specific
A620T mutation in Plg, also known as Plg-Tochigi, originally identified in a
patient with recurrent venous thromboembolism, causes dysplasminogenemia with
reduced plasmin activity. The Plg-A620T mutation is present in 3-4% of
individuals in East Asian populations, and as many as 50,000 Japanese are
estimated to be homozygous for the mutant 620T allele. In the present study, to
understand the changes of thrombotic phenotypes in individuals with the mutant
620T allele, we generated knock-in mice carrying the homozygous Plg-A622T
mutation (PlgT/T), an equivalent to the A620T mutation in human Plg. PlgT/T mice
grew normally but showed severely reduced plasmin activity activated by
urokinase, equivalent to ~8% of that in wild-type mice. In vitro fibrin clot
lysis in plasma was significantly slower in PlgT/T mice than in wild-type mice.
However, all experimental models of electrolytic deep vein thrombosis, tissue
factor-induced pulmonary embolism, transient focal brain ischaemic stroke, or
skin-wound healing showed largely similar phenotypes between PlgT/T mice and wild
type mice. Protein S-K196E mutation (Pros1E/E) is a race-specific genetic risk
factor for venous thromboembolism. Coexistence in mice of PlgT/T and Pros1E/E did
not affect pulmonary embolism symptoms, compared with those in Pros1E/E mice.
Hence, the present study showed that the Plg-A622T mutation, which confers ~8%
plasmin activity, does not increase the risk of thrombotic diseases in mice under
experimental thrombotic conditions and does not modify the thrombotic phenotype
observed in Pros1E/E mice. PlgT/T mice can be used to investigate the potential
pathophysiological impact of the Plg-A620T mutation.
PMID- 28686707
TI - Molecular characterization of occult hepatitis B virus infection in patients with
end-stage liver disease in Colombia.
AB - BACKGROUND: Hepatitis B virus (HBV) occult infection (OBI) is a risk factor to be
taken into account in transfusion, hemodialysis and organ transplantation. The
aim of this study was to identify and characterize at the molecular level OBI
cases in patients with end-stage liver disease. METHODS: Sixty-six liver samples
were obtained from patients with diagnosis of end-stage liver disease submitted
to liver transplantation in Medellin (North West, Colombia). Samples obtained
from patients who were negative for the surface antigen of HBV (n = 50) were
tested for viral DNA detection by nested PCR for ORFs S, C, and X and confirmed
by Southern-Blot. OBI cases were analyzed by sequencing the viral genome to
determine the genotype and mutations; additionally, viral genome integration
events were examined by the Alu-PCR technique. RESULTS: In five cases out of 50
patients (10%) the criteria for OBI was confirmed. HBV genotype F (subgenotypes
F1 and F3), genotype A and genotype D were characterized in liver samples. Three
integration events in chromosomes 5q14.1, 16p13 and 20q12 affecting Receptor-type
tyrosine-protein phosphatase T, Ras Protein Specific Guanine Nucleotide Releasing
Factor 2, and the zinc finger 263 genes were identified in two OBI cases.
Sequence analysis of the viral genome of the 5 OBI cases showed several punctual
missense and nonsense mutations affecting ORFs S, P, Core and X. CONCLUSIONS:
This is the first characterization of OBI in patients with end-stage liver
disease in Colombia. The OBI cases were identified in patients with HCV infection
or cryptogenic cirrhosis. The integration events (5q14.1, 16p13 and 20q12)
described in this study have not been previously reported. Further studies are
required to validate the role of mutations and integration events in OBI
pathogenesis.
PMID- 28686708
TI - Drosophila lines with mutant and wild type human TDP-43 replacing the endogenous
gene reveals phosphorylation and ubiquitination in mutant lines in the absence of
viability or lifespan defects.
AB - Mutations in TDP-43 are associated with proteinaceous inclusions in neurons and
are believed to be causative in neurodegenerative diseases such as frontotemporal
dementia or amyotrophic lateral sclerosis. Here we describe a Drosophila system
where we have engineered the genome to replace the endogenous TDP-43 orthologue
with wild type or mutant human TDP-43(hTDP-43). In contrast to other models,
these flies express both mutant and wild type hTDP-43 at similar levels to those
of the endogenous gene and importantly, no age-related TDP-43 accumulation
observed among all the transgenic fly lines. Immunoprecipitation of TDP-43 showed
that flies with hTDP-43 mutations had increased levels of ubiquitination and
phosphorylation of the hTDP-43 protein. Furthermore, histologically, flies
expressing hTDP-43 M337V showed global, robust neuronal staining for phospho-TDP.
All three lines: wild type hTDP-43, -G294A and -M337V were homozygous viable,
with no defects in development, life span or behaviors observed. The primary
behavioral defect was that flies expressing either hTDP-43 G294A or M337V showed
a faster decline with age in negative geotaxis. Together, these observations
implied that neurons could handle these TDP-43 mutations by phosphorylation- and
ubiquitin-dependent proteasome systems, even in a background without the wild
type TDP-43. Our findings suggest that these two specific TDP-43 mutations are
not inherently toxic, but may require additional environmental or genetic factors
to affect longevity or survival.
PMID- 28686709
TI - Axial length changes in highly myopic eyes and influence of myopic macular
complications in Japanese adults.
AB - PURPOSE: To investigate changes of the axial length in normal eyes and highly
myopic eyes and influence of myopic macular complications in Japanese adults.
STUDY DESIGN: Retrospective longitudinal case series. METHODS: The changes in the
axial length of 316 eyes from 316 patients (mean age, 63.8 +/- 9.0 years; range,
34-82; 240 females) examined using IOLMaster with a follow-up period of at least
1 year were studied. This study included 85 non-highly myopic eyes (|refractive
error| <= 5 diopters; 63 females; non-highly myopic group), 165 highly myopic
eyes (refractive error <= -6 diopters or axial length >= 26 mm; 124 females)
without macular complications (no complications group), 32 eyes (25 females) with
myopic traction maculopathy (MTM group), and 34 eyes (28 females) with myopic
choroidal neovascularization (CNV group). RESULTS: All groups showed a
significant increase in the axial length during the follow-up period (mean follow
up, 28.7 +/- 16.8 months; range, 12-78) (P < 0.01). Changes in the axial
length/year in the no complications group (0.041 +/- 0.05 mm) were significantly
greater than those in the non-highly myopic group (0.007 +/- 0.02 mm) (P <
0.0001). Furthermore, changes in the CNV group (0.081 +/- 0.04 mm) were
significantly greater than those in the no complications (P < 0.0001) and MTM
(0.040 +/- 0.05 mm) (P = 0.0059) groups, whereas no significant difference was
found between the changes in the MTM and no complications groups (P = 0.91).
Multiple regression analyses indicated that CNV eyes (P < 0.0001) and female
patients' eyes (P = 0.04) showed greater changes in the axial length/year.
CONCLUSIONS: All groups showed an increase in the axial length, which was greater
for highly myopic eyes. In particular, CNV eyes showed greater increases,
indicating that larger changes in the axial length may require careful follow-up.
PMID- 28686710
TI - Autoimmunity and allergy control in adults submitted to complete thymectomy early
in infancy.
AB - The contribution of the decline in thymic activity for the emergence of
autoimmunity is still debatable. Immune-competent adults submitted to complete
thymectomy early in life provide a unique model to address this question. We
applied here strict criteria to identify adults lacking thymic activity based on
sjTREC levels, to exclude thymic rebound and/or ectopic thymuses. In agreement,
they featured severe naive CD4 T-cell depletion and contraction of T-cell
receptor diversity. Notwithstanding this, there was neither increased incidence
of autoimmune disease in comparison with age-matched controls nor significant
changes in their IgG/IgA/IgM/IgE autoreactivity profiles, as assessed through
extensive arrays. We reasoned that the observed relative preservation of the
regulatory T-cell compartment, including maintenance of naive regulatory CD4 T
cells, may contribute to limit the emergence of autoimmunity upon thymectomy. Our
findings have implications in other clinical settings with impaired thymic
activity, and are particularly relevant to studies of autoimmunity in ageing.
PMID- 28686711
TI - Co-ordinated spatial propagation of blood plasma clotting and fibrinolytic
fronts.
AB - Fibrinolysis is a cascade of proteolytic reactions occurring in blood and soft
tissues, which functions to disintegrate fibrin clots when they are no more
needed. In order to elucidate its regulation in space and time, fibrinolysis was
investigated using an in vitro reaction-diffusion experimental model of blood
clot formation and dissolution. Clotting was activated by a surface with
immobilized tissue factor in a thin layer of recalcified blood plasma
supplemented with tissue plasminogen activator (TPA), urokinase plasminogen
activator or streptokinase. Formation and dissolution of fibrin clot was
monitored by videomicroscopy. Computer systems biology model of clot formation
and lysis was developed for data analysis and experimental planning. Fibrin clot
front propagated in space from tissue factor, followed by a front of clot
dissolution propagating from the same source. Velocity of lysis front propagation
linearly depended on the velocity clotting front propagation (correlation r2 =
0.91). Computer model revealed that fibrin formation was indeed the rate-limiting
step in the fibrinolysis front propagation. The phenomenon of two fronts which
switched the state of blood plasma from liquid to solid and then back to liquid
did not depend on the fibrinolysis activator. Interestingly, TPA at high
concentrations began to increase lysis onset time and to decrease lysis
propagation velocity, presumably due to plasminogen depletion. Spatially non
uniform lysis occurred simultaneously with clot formation and detached the clot
from the procoagulant surface. These patterns of spatial fibrinolysis provide
insights into its regulation and might explain clinical phenomena associated with
thrombolytic therapy.
PMID- 28686712
TI - Development and characterization of a new set of genomic microsatellite markers
in rice bean (Vigna umbellata (Thunb.) Ohwi and Ohashi) and their utilization in
genetic diversity analysis of collections from North East India.
AB - Rice bean [Vigna umbellate (Thumb.) Ohwi and Ohashi] is an underutilized crop
believed to be domesticated in the Myanmar-Thailand region of Asia. In India,
rice bean is mainly cultivated in the North-Eastern Hills, which is a hotspot for
biological diversity. A 5' anchored PCR was used to develop microsatellite
markers in rice bean. Twenty-eight specific primer pairs were designed and
employed to characterize sixty five ricebean accessions collected from North East
India. A total of 179 alleles were amplified with an average of 6.393 alleles per
locus. The gene diversity was high (mean 0.534) in the accessions collected from
Darjeeling, Nagaland and Manipur, which are bordering areas with East Nepal and
Myanmar, respectively. Exceptionally high outcrossing rate was observed in the
entire population. Population structure analysis identified three distinct
clusters in which accessions collected from areas bordering Myanmar and East
Nepal grouped separately. Using a combination of STRUCTURE and Principal
Coordinate Analysis, relative affinity of the intermediate accessions could be
established. However, differences in allelic counts among populations were non
significant. The results showed that there is a high level of genetic diversity
within the accessions, with high outcrossing rate.
PMID- 28686715
TI - Use of multiple data sources to estimate hepatitis C seroprevalence among
prisoners: A retrospective cohort study.
AB - Hepatitis C is a major cause of preventable morbidity and mortality. Prisoners
are a key population for hepatitis C control programs, and with the advent of
highly effective therapies, prisons are increasingly important sites for
hepatitis C diagnosis and treatment. Accurate estimates of hepatitis C prevalence
among prisoners are needed in order to plan and resource service provision,
however many prevalence estimates are based on surveys compromised by limited and
potentially biased participation. We aimed to compare estimates derived from
three different data sources, and to assess whether the use of self-report as a
supplementary data source may help researchers assess the risk of selection bias.
We used three data sources to estimate the prevalence of hepatitis C antibodies
in a large cohort of Australian prisoners-prison medical records, self-reported
status during a face-to-face interview prior to release from prison, and data
from a statewide notifiable conditions surveillance system. Of 1,315
participants, 33.8% had at least one indicator of hepatitis C seropositivity,
however less than one third of these (9.5% of the entire cohort) were identified
by all three data sources. Among participants of known status, self-report had a
sensitivity of 80.1% and a positive predictive value of 97.8%. Any one data
source used in isolation would have under-estimated the prevalence of hepatitis C
in this cohort. Using multiple data sources in studies of hepatitis C
seroprevalence among prisoners may improve case detection and help researchers
assess the risk of selection bias due to non-participation in serological
testing.
PMID- 28686713
TI - Transcriptome-wide comparison of the impact of Atoh1 and miR-183 family on
pluripotent stem cells and multipotent otic progenitor cells.
AB - Over 5% of the global population suffers from disabling hearing loss caused by
multiple factors including aging, noise exposure, genetic predisposition, or use
of ototoxic drugs. Sensorineural hearing loss is often caused by the loss of
sensory hair cells (HCs) of the inner ear. A barrier to hearing restoration after
HC loss is the limited ability of mammalian auditory HCs to spontaneously
regenerate. Understanding the molecular mechanisms orchestrating HC development
is expected to facilitate cell replacement therapies. Multiple events are known
to be essential for proper HC development including the expression of Atoh1
transcription factor and the miR-183 family. We have developed a series of
vectors expressing the miR-183 family and/or Atoh1 that was used to transfect two
different developmental cell models: pluripotent mouse embryonic stem cells
(mESCs) and immortalized multipotent otic progenitor (iMOP) cells representing an
advanced developmental stage. Transcriptome profiling of transfected cells show
that the impact of Atoh1 is contextually dependent with more HC-specific effects
on iMOP cells. miR-183 family expression in combination with Atoh1 not only
appears to fine tune gene expression in favor of HC fate, but is also required
for the expression of some HC-specific genes. Overall, the work provides novel
insight into the combined role of Atoh1 and the miR-183 family during HC
development that may ultimately inform strategies to promote HC regeneration or
maintenance.
PMID- 28686714
TI - Experimental Mycobacterium bovis infection in three white rhinoceroses
(Ceratotherium simum): Susceptibility, clinical and anatomical pathology.
AB - Tuberculosis caused by Mycobacterium bovis is endemic in the African buffalo
(Syncerus caffer) population in the Kruger National Park and other conservation
areas in South Africa. The disease has been diagnosed in a total of 21 free
ranging or semi-free ranging wildlife species in the country with highly variable
presentations in terms of clinical signs as well as severity and distribution of
tuberculous lesions. Most species are spillover or dead-end hosts without
significant role in the epidemiology of the disease. White rhinoceroses
(Ceratotherium simum) are translocated from the Kruger National Park in
substantial numbers every year and a clear understanding of their risk to
manifest overt tuberculosis disease and to serve as source of infection to other
species is required. We report the findings of experimental infection of three
white rhinoceroses with a moderately low dose of a virulent field isolate of
Mycobacterium bovis. None of the animals developed clinical signs or disseminated
disease. The susceptibility of the white rhinoceros to bovine tuberculosis was
confirmed by successful experimental infection based on the ante mortem isolation
of M. bovis from the respiratory tract of one rhinoceros, the presence of acid
fast organisms and necrotizing granulomatous lesions in the tracheobronchial
lymph nodes and the detection of M. bovis genetic material by PCR in the lungs of
two animals.
PMID- 28686717
TI - Correction: Recessive coding and regulatory mutations in FBLIM1 underlie the
pathogenesis of chronic recurrent multifocal osteomyelitis (CRMO).
AB - [This corrects the article DOI: 10.1371/journal.pone.0169687.].
PMID- 28686716
TI - GSR is not essential for the maintenance of antioxidant defenses in mouse
cochlea: Possible role of the thioredoxin system as a functional backup for GSR.
AB - Glutathione reductase (GSR), a key member of the glutathione antioxidant defense
system, converts oxidized glutathione (GSSG) to reduced glutathione (GSH) and
maintains the intracellular glutathione redox state to protect the cells from
oxidative damage. Previous reports have shown that Gsr deficiency results in
defects in host defense against bacterial infection, while diquat induces renal
injury in Gsr hypomorphic mice. In flies, overexpression of GSR extended lifespan
under hyperoxia. In the current study, we investigated the roles of GSR in
cochlear antioxidant defense using Gsr homozygous knockout mice that were
backcrossed onto the CBA/CaJ mouse strain, a normal-hearing strain that does not
carry a specific Cdh23 mutation that causes progressive hair cell degeneration
and early onset of hearing loss. Gsr-/- mice displayed a significant decrease in
GSR activity and GSH/GSSG ratios in the cytosol of the inner ears. However, Gsr
deficiency did not affect ABR (auditory brainstem response) hearing thresholds,
wave I amplitudes or wave I latencies in young mice. No histological
abnormalities were observed in the cochlea of Gsr-/- mice. Furthermore, there
were no differences in the activities of cytosolic glutathione-related enzymes,
including glutathione peroxidase and glutamate-cysteine ligase, or the levels of
oxidative damage markers in the inner ears between WT and Gsr-/- mice. In
contrast, Gsr deficiency resulted in increased activities of cytosolic
thioredoxin and thioredoxin reductase in the inner ears. Therefore, under normal
physiological conditions, GSR is not essential for the maintenance of antioxidant
defenses in mouse cochlea. Given that the thioredoxin system is known to reduce
GSSG to GSH in multiple species, our findings suggest that the thioredoxin system
can support GSSG reduction in the mouse peripheral auditory system.
PMID- 28686718
TI - Morphological variation, phylogenetic relationships, and geographic distribution
of the Baenidae (Testudines), based on new specimens from the Uinta Formation
(Uinta Basin), Utah (USA).
AB - We described newly discovered baenid specimens from the Uintan North American
Land Mammal Age (NALMA), in the Uinta Formation, Uinta Basin, Utah. These
specimens include a partial skull and several previously undescribed postcranial
elements of Baena arenosa, and numerous well-preserved shells of B. arenosa and
Chisternon undatum. Baenids from the Uintan NALMA (46.5-40 Ma) are critical in
that they provide valuable insight into the morphology and evolution of the
diverse and speciose baenid family near the end of its extensive radiation, just
prior to the disappearance of this clade from the fossil record. These Uintan
specimens greatly increase the known variation in these late-surviving taxa and
indicate that several characters thought to define these species should be
reassessed. The partial cranium of B. arenosa, including portions of the
basicranium, neurocranium, face, and lower jaw, was recently recovered from Uinta
B sediments. While its morphology is consistent with known specimens of B.
arenosa, we observed several distinct differences: a crescent-shaped condylus
occipitalis that is concave dorsally, tuberculum basioccipitale that flare out
laterally, and a distinct frontal-nasal suture. The current sample of plastral
and carapacial morphology considerably expands the documented variation in the
hypodigms of B. arenosa and C. undatum. Novel shell characters observed include
sigmoidal extragular-humeral sulci, and small, subtriangular gular scutes.
Subadult specimens reveal ontogenetic processes in both taxa, and demonstrate
that diagnostic morphological differences between them were present from an early
developmental age.
PMID- 28686719
TI - Evidence for complex contagion models of social contagion from observational
data.
AB - Social influence can lead to behavioural 'fads' that are briefly popular and
quickly die out. Various models have been proposed for these phenomena, but
empirical evidence of their accuracy as real-world predictive tools has so far
been absent. Here we find that a 'complex contagion' model accurately describes
the spread of behaviours driven by online sharing. We found that standard,
'simple', contagion often fails to capture both the rapid spread and the long
tails of popularity seen in real fads, where our complex contagion model
succeeds. Complex contagion also has predictive power: it successfully predicted
the peak time and duration of the ALS Icebucket Challenge. The fast spread and
longer duration of fads driven by complex contagion has important implications
for activities such as publicity campaigns and charity drives.
PMID- 28686720
TI - Free cholesterol and cholesterol esters in bovine oocytes: Implications in
survival and membrane raft organization after cryopreservation.
AB - Part of the damage caused by cryopreservation of mammalian oocytes occurs at the
plasma membrane. The addition of cholesterol to cell membranes as a strategy to
make it more tolerant to cryopreservation has been little addressed in oocytes.
In order to increase the survival of bovine oocytes after cryopreservation, we
proposed not only to increase cholesterol level of oocyte membranes before
vitrification but also to remove the added cholesterol after warming, thus
recovering its original level. Results from our study showed that modulation of
membrane cholesterol by methyl-beta-cyclodextrin (MbetaCD) did not affect the
apoptotic status of oocytes and improved viability after vitrification yielding
levels of apoptosis closer to those of fresh oocytes. Fluorometric measurements
based on an enzyme-coupled reaction that detects both free cholesterol (membrane)
and cholesteryl esters (stored in lipid droplets), revealed that oocytes and
cumulus cells present different levels of cholesterol depending on the seasonal
period. Variations at membrane cholesterol level of oocytes were enough to
account for the differences found in total cholesterol. Differences found in
total cholesterol of cumulus cells were explained by the differences found in
both the content of membrane cholesterol and of cholesterol esters. Cholesterol
was incorporated into the oocyte plasma membrane as evidenced by comparative
labeling of a fluorescent cholesterol. Oocytes and cumulus cells increased
membrane cholesterol after incubation with MbetaCD/cholesterol and recovered
their original level after cholesterol removal, regardless of the season.
Finally, we evaluated the effect of vitrification on the putative raft molecule
GM1. Cholesterol modulation also preserved membrane organization by maintaining
ganglioside level at the plasma membrane. Results suggest a distinctive
cholesterol metabolic status of cumulus-oocyte complexes (COCs) among seasons and
a dynamic organizational structure of cholesterol homeostasis within the COC.
Modulation of membrane cholesterol by MbetaCD improved survival of bovine oocytes
and preserved integrity of GM1-related rafts after vitrification.
PMID- 28686721
TI - Systemic PD149163, a neurotensin receptor 1 agonist, decreases methamphetamine
self-administration in DBA/2J mice without causing excessive sedation.
AB - Methamphetamine (METH) is a psychostimulant that exhibits significant abuse
potential. Although METH addiction is a major health and societal concern, no
drug is currently approved for its therapeutic management. METH activates the
central dopaminergic "reward" circuitry, and with repeated use increases levels
of the neuromodulatory peptide neurotensin in the nucleus accumbens and ventral
tegmental area. Previous studies in rats suggest that neurotensin agonism
decreases METH self-administration, but these studies did not examine the effect
of neurotensin agonism on the pattern of self-administration or open field
locomotion. In our studies, we established intravenous METH self-administration
in male, DBA/2J mice (fixed ratio 3, 2 hr sessions) and examined the effect of
pretreatment with the NTS1 receptor agonist PD149163 on METH self-administration
behavior. Locomotion following PD149163 was also measured up to 2 hours after
injection on a rotarod and in an open field. Pretreatment with PD149163 (0.05 and
0.10 mg/kg, s.c.) significantly decreased METH self-administration. The pattern
of responding suggested that PD149163 decreased motivation to self-administer
METH initially in the session with more normal intake in the second hour of
access. Voluntary movement in the open-field was significantly decreased by both
0.05 and 0.10 mg/kg (s.c.) PD149163 from 10-120 minutes after injection, but
rotarod performance suggested that PD149163 did not cause frank sedation. These
results suggest that a systemically delivered NTS1 receptor agonist decreases
METH self-administration in mice. The pattern of self-administration suggests
that PD149163 may acutely decrease motivation to self-administer METH before the
drug is experienced, but cannot rule out that depression of voluntary movement
plays a role in the decreased self-administration.
PMID- 28686723
TI - Correction: T1R3 homomeric sweet taste receptor regulates adipogenesis through
Galphas-mediated microtubules disassembly and Rho activation in 3T3-L1 cells.
AB - [This corrects the article DOI: 10.1371/journal.pone.0176841.].
PMID- 28686722
TI - The changes of gut microbiota after acute myocardial infarction in rats.
AB - Recent studies suggested that gut microbiota was involved in the development of
coronary artery disease. However, the changes of gut microbiota following acute
myocardial infarction (AMI) remain unknown. In this study, a total of 66 male
Wistar rats were randomly divided into control, AMI and SHAM groups. The controls
(n = 6) were sacrificed after anesthesia. The AMI model was built by ligation of
left anterior descending coronary artery. The rats of AMI and SHAM groups were
sacrificed at 12 h, 1 d, 3 d, 7 d and 14 d post-operation respectively. Gut
microbiota was analyzed by 16S rDNA high throughput sequencing. The gut barrier
injuries were evaluated through histopathology, transmission electron microscope
and immunohistochemical staining. The richness of gut microbiota was
significantly higher in AMI group than SHAM group at 7 d after AMI (P<0.05).
Principal coordinate analysis with unweighted UniFrac distances revealed
microbial differences between AMI and SHAM groups at 7 d. The gut barrier
impairment was also the most significant at 7 d post-AMI. We further identified
the differences of microorganisms between AMI and SHAM group at 7 d. The
abundance of Synergistetes phylum, Spirochaetes phylum, Lachnospiraceae family,
Syntrophomonadaceae family and Tissierella Soehngenia genus was higher in AMI
group compared with SHAM group at 7 d post-operation (q<0.05). Our study showed
the changes of gut microbiota at day 7 post AMI which was paralleled with
intestinal barrier impairment. We also identified the microbial organisms that
contribute most.
PMID- 28686724
TI - Dipeptidyl peptidase-4 inhibitor gemigliptin protects against vascular
calcification in an experimental chronic kidney disease and vascular smooth
muscle cells.
AB - Although dipeptidyl peptidase-4 inhibitors, a class of antidiabetic drugs, have
various pleiotropic effects, it remains undetermined whether gemigliptin has a
beneficial effect on vascular calcification. Therefore, this study was performed
to evaluate the effect of gemigliptin on vascular calcification in a rat model of
adenine-induced chronic kidney disease and in cultured vascular smooth muscle
cells. Gemigliptin attenuated calcification of abdominal aorta and expression of
RUNX2 in adenine-induced chronic kidney disease rats. In cultured vascular smooth
muscle cells, phosphate-induced increase in calcium content was reduced by
gemigliptin. Gemigliptin reduced phosphate-induced PiT-1 mRNA expression,
reactive oxygen species generation, and NADPH oxidase mRNA expression (p22phox
and NOX4). The reduction of oxidative stress by gemigliptin was associated with
the downregulation of phospho-PI3K/AKT expression. High phosphate increased the
expression of frizzled-3 (FDZ3) and decreased the expression of dickkopf-related
protein-1 (DKK-1) in the Wnt pathway. These changes were attenuated by
gemigliptin treatment. Gemigliptin restored the decreased expression of vascular
smooth muscle cells markers (alpha-SMA and SM22alpha) and increased expression of
osteogenic makers (CBFA1, OSX, E11, and SOST) induced by phosphate. In
conclusion, gemigliptin attenuated vascular calcification and osteogenic trans
differentiation in vascular smooth muscle cells via multiple steps including
downregulation of PiT-1 expression and suppression of reactive oxygen species
generation, phospho-PI3K/AKT, and the Wnt signaling pathway.
PMID- 28686725
TI - Persistence of subclinical deformed wing virus infections in honeybees following
Varroa mite removal and a bee population turnover.
AB - Deformed wing virus (DWV) is a lethal virus of honeybees (Apis mellifera)
implicated in elevated colony mortality rates worldwide and facilitated through
vector transmission by the ectoparasitic mite Varroa destructor. Clinical,
symptomatic DWV infections are almost exclusively associated with high virus
titres during pupal development, usually acquired through feeding by Varroa mites
when reproducing on bee pupae. Control of the mite population, generally through
acaricide treatment, is essential for breaking the DWV epidemic and minimizing
colony losses. In this study, we evaluated the effectiveness of remedial mite
control on clearing DWV from a colony. DWV titres in adult bees and pupae were
monitored at 2 week intervals through summer and autumn in acaricide-treated and
untreated colonies. The DWV titres in Apistan treated colonies was reduced 1000
fold relative to untreated colonies, which coincided with both the removal of
mites and also a turnover of the bee population in the colony. This adult bee
population turnover is probably more critical than previously realized for
effective clearing of DWV infections. After this initial reduction, subclinical
DWV titres persisted and even increased again gradually during autumn,
demonstrating that alternative non-Varroa transmission routes can maintain the
DWV titres at significant subclinical levels even after mite removal. The
implications of these results for practical recommendations to mitigate
deleterious subclinical DWV infections and improving honeybee health management
are discussed.
PMID- 28686726
TI - Examining the gender difference in the association between metabolic syndrome and
the mean leukocyte telomere length.
AB - The mechanism of cellular aging likely involves decreased telomere length and is
associated with age-related diseases such as cardiovascular disease. Metabolic
syndrome (MetS) is an important risk factor for CVD. The purpose of this study
was to investigate the association between LTL and MetS. We evaluated 7370
participants in the National Health and Nutrition Examination Survey (1999-2002).
The association between LTL and individual MetS components and the number of MetS
components was analyzed by multivariable regression models, adjusting for gender,
race/ethnicity, albumin, C-reactive protein, alanine transaminase, uric acid and
medical condition. An increase in the number of MetS components was strongly
associated with shorter telomere length, especially in female participants (p for
trend < 0.05). In addition, triglycerides were negatively associated with LTL in
female participants (p < 0.001). Waist circumstance was associated with decreased
LTL (p < 0.05) in both males and females. In summary, our study indicated that an
increment of MetS component is strongly associated with shorter LTL, especially
in the female population.
PMID- 28686727
TI - The Pseudomonas aeruginosa CrcZ RNA interferes with Hfq-mediated riboregulation.
AB - The RNA chaperone Hfq regulates virulence and metabolism in the opportunistic
pathogen Pseudomonas aeruginosa. During carbon catabolite repression (CCR) Hfq
together with the catabolite repression control protein Crc can act as a
translational repressor of catabolic genes. Upon relief of CCR, the level of the
Hfq-titrating RNA CrcZ is increasing, which in turn abrogates Hfq-mediated
translational repression. As the interdependence of Hfq-mediated and RNA based
control mechanisms is poorly understood, we explored the possibility whether the
regulatory RNA CrcZ can interfere with riboregulation. We first substantiate that
the P. aeruginosa Hfq is proficient and required for riboregulation of the
transcriptional activator gene antR by the small RNA PrrF1-2. Our studies further
revealed that CrcZ can interfere with PrrF1-2/Hfq-mediated regulation of antR.
The competition for Hfq can be rationalized by the higher affinity of Hfq for
CrcZ than for antR mRNA.
PMID- 28686729
TI - Correction: Physiological responses and external validity of a new setting for
taekwondo combat simulation.
AB - [This corrects the article DOI: 10.1371/journal.pone.0171553.].
PMID- 28686728
TI - Regulation of platelet-activating factor-mediated protein tyrosine phosphatase 1B
activation by a Janus kinase 2/calpain pathway.
AB - Atherosclerosis is a pro-inflammatory condition underlying many cardiovascular
diseases. Platelet-activating factor (PAF) and interleukin 6 (IL-6) are actively
involved in the onset and progression of atherosclerotic plaques. The involvement
of monocyte-derived macrophages is well characterized in the installation of
inflammatory conditions in the plaque, but less is known about the contribution
of monocyte-derived dendritic cells (Mo-DCs). In the same way, the involvement of
calcium, phospholipase C and A2 in PAF-induced IL-6 production, in different
cells types, has been shown; however, the importance of the Jak/STAT pathway and
its regulation by protein-tyrosine phosphatases in this response have not been
addressed. In this study, we report that PAF stimulates PTP1B activity via Jak2,
thereby modulating PAF-induced IL-6 production. Using HEK 293 cells stably
transfected with the PAF receptor in order to discriminate the pathway
components, our results suggest that Jak2 modulates PAF-induced IL-6 production
via both positive and negative pathways. Jak2 kinase activity was necessary for
maximal transactivation of the IL-6 promoter, as seen by luciferase assays,
whereas the same kinase also downregulated this promoter transactivation through
the activation of a calcium/calpain/PTP1B pathway. The same pathways were
operational in monocyte-derived dendritic cells, since PAF-induced PTP1B
activation negatively regulated PAF-induced IL-6 mRNA production and, in
addition, Jak2 activated calpain, one of the components involved in PAF-induced
PTP1B activation. Results obtained in this study indicate that Jak2 activation is
important for maximal IL-6 promoter transactivation by PAF and that PTP1B is
involved in the negative regulation of this transactivation. However, PTP1B does
not directly regulate Jak2 activation, but rather Jak2 regulates PAF-induced
PTP1B activation.
PMID- 28686730
TI - Correction: Real-time cell toxicity profiling of Tox21 10K compounds reveals
cytotoxicity dependent toxicity pathway linkage.
AB - [This corrects the article DOI: 10.1371/journal.pone.0177902.].
PMID- 28686731
TI - Evaluation of nine genotypes of oilseed rape (Brassica napus L.) for larval
infestation and performance of rape stem weevil (Ceutorhynchus napi Gyll.).
AB - The rape stem weevil, Ceutorhynchus napi Gyll., is a serious pest of winter
oilseed rape (Brassica napus L.) crops in Europe causing severe yield loss. In
currently used oilseed rape cultivars no resistance to C. napi has been
identified. Resynthesized lines of B. napus have potential to broaden the genetic
variability and may improve resistance to insect pests. In this study, the
susceptibility to C. napi of three cultivars, one breeding line and five
resynthesized lines of oilseed rape was compared in a semi-field plot experiment
under multi-choice conditions. Plant acceptance for oviposition was estimated by
counting the number of C. napi larvae in stems. The larval instar index and the
dry body mass were assessed as indicators of larval performance. The extent of
larval feeding within stems was determined by the stem injury coefficient.
Morphological stem traits and stem contents of glucosinolates were assessed as
potential mediators of resistance. The resynthesized line S30 had significantly
fewer larvae than the cultivars Express617 and Visby and the resynthesized lines
L122 and L16. The low level of larval infestation in S30 was associated with a
low larval instar and stem injury index. Low numbers of larvae were not
correlated with the length or diameter of stems, and the level of stem
glucosinolates. As indicated by the low larval infestation and slow larval
development the resistance of S30 to C. napi is based on both antixenotic and
antibiotic properties of the genotypes. The resynthesized line S30 should
therefore be introduced into B. napus breeding programs to enhance resistance
against C. napi.
PMID- 28686732
TI - Correction: Unhealthy habits persist: The ongoing presence of modifiable risk
factors for disease in women.
AB - [This corrects the article DOI: 10.1371/journal.pone.0173603.].
PMID- 28686734
TI - Reassessing rainfall in the Luquillo Mountains, Puerto Rico: Local and global
ecohydrological implications.
AB - Mountains receive a greater proportion of precipitation than other environments,
and thus make a disproportionate contribution to the world's water supply. The
Luquillo Mountains receive the highest rainfall on the island of Puerto Rico and
serve as a critical source of water to surrounding communities. The area's role
as a long-term research site has generated numerous hydrological, ecological, and
geological investigations that have been included in regional and global
overviews that compare tropical forests to other ecosystems. Most of the forest-
and watershed-wide estimates of precipitation (and evapotranspiration, as
inferred by a water balance) have assumed that precipitation increases
consistently with elevation. However, in this new analysis of all known current
and historical rain gages in the region, we find that similar to other
mountainous islands in the trade wind latitudes, leeward (western) watersheds in
the Luquillo Mountains receive lower mean annual precipitation than windward
(eastern) watersheds. Previous studies in the Luquillo Mountains have therefore
overestimated precipitation in leeward watersheds by up to 40%. The Icacos
watershed, however, despite being located at elevations 200-400 m below the
tallest peaks and to the lee of the first major orographic barrier, receives some
of the highest precipitation. Such lee-side enhancement has been observed in
other island mountains of similar height and width, and may be caused by several
mechanisms. Thus, the long-reported discrepancy of unrealistically low rates of
evapotranspiration in the Icacos watershed is likely caused by previous
underestimation of precipitation, perhaps by as much as 20%. Rainfall/runoff
ratios in several previous studies suggested either runoff excess or runoff
deficiency in Luquillo watersheds, but this analysis suggests that in fact they
are similar to other tropical watersheds. Because the Luquillo Mountains often
serve as a wet tropical archetype in global assessments of basic ecohydrological
processes, these revised estimates are relevant to regional and global
assessments of runoff efficiency, hydrologic effects of reforestation, geomorphic
processes, and climate change.
PMID- 28686733
TI - The short mRNA isoform of the immunoglobulin superfamily, member 1 gene encodes
an intracellular glycoprotein.
AB - Mutations in the immunoglobulin superfamily, member 1 gene (IGSF1/Igsf1) cause an
X-linked form of central hypothyroidism. The canonical form of IGSF1 is a
transmembrane glycoprotein with 12 immunoglobulin (Ig) loops. The protein is co
translationally cleaved into two sub-domains. The carboxyl-terminal domain (CTD),
which contains the last 7 Ig loops, is trafficked to the plasma membrane. Most
pathogenic mutations in IGSF1 map to the portion of the gene encoding the CTD.
IGSF1/Igsf1 encodes a variety of transcripts. A little studied, but abundant
splice variant encodes a truncated form of the protein, predicted to contain the
first 2 Ig loops of the full-length IGSF1. The protein (hereafter referred to as
IGSF1 isoform 2 or IGSF1-2) is likely retained in most individuals with IGSF1
mutations. Here, we characterized basic biochemical properties of the protein as
a foray into understanding its potential function. IGSF1-2, like the IGSF1-CTD,
is a glycoprotein. In both mouse and rat, the protein is N-glycosylated at a
single asparagine residue in the first Ig loop. Contrary to earlier predictions,
neither the murine nor rat IGSF1-2 is secreted from heterologous or homologous
cells. In addition, neither protein associates with the plasma membrane. Rather,
IGSF1-2 appears to be retained in the endoplasmic reticulum. Whether the protein
plays intracellular functions or is trafficked through the secretory pathway
under certain physiologic or pathophysiologic conditions has yet to be
determined.
PMID- 28686735
TI - Characteristics and origin of the relatively high-quality tight reservoir in the
Silurian Xiaoheba Formation in the southeastern Sichuan Basin.
AB - A mature understanding of the sandstone gas reservoir in the Xiaoheba Formation
in the southeastern Sichuan Basin remains lacking. To assess the reservoir
characteristics and the origin of the high-quality reservoir in the Xiaoheba
Formation, this paper uses systematic field investigations, physical property
analysis, thin section identification, scanning electron microscopy and electron
microprobe methods. The results indicate that the Xiaoheba sandstone is an ultra
tight and ultra-low permeability reservoir, with an average porosity of 2.97% and
an average permeability of 0.56*10-3 MUm2. This promising reservoir is mainly
distributed in the Lengshuixi and Shuangliuba regions and the latter has a
relatively high-quality reservoir with an average porosity of 5.28% and average
permeability of 0.53*10-3 MUm2. The reservoir space comprises secondary
intergranular dissolved pores, moldic pores and fractures. Microfacies, feldspar
dissolution and fracture connectivity control the quality of this reservoir. The
relatively weak compaction and cementation in the interbedded delta front distal
bar and interdistributary bay microfacies indirectly protected the primary
intergranular pores and enhanced late-stage dissolution. Late-stage potassium
feldspar dissolution was controlled by the early-stage organic acid dissolution
intensity and the distance from the hydrocarbon generation center. Early-stage
fractures acted as pathways for organic acid migration and were therefore
important factors in the formation of the reservoir. Based on these observations,
the area to the west of the Shuangliuba and Lengshuixi regions has potential for
gas exploration.
PMID- 28686736
TI - Higher mineralized bone volume is associated with a lower plain X-Ray vascular
calcification score in hemodialysis patients.
AB - BACKGROUND AND OBJECTIVES: In dialysis patients, there is an increasing evidence
that altered bone metabolism is associated with cardiovascular calcifications.
The main objective of this study was to analyse, in hemodialysis patients, the
relationships between bone turnover, mineralization and volume, evaluated in bone
biopsies, with a plain X-ray vascular calcification score. DESIGN, SETTING,
PARTICIPANTS AND MEASUREMENTS: In a cross-sectional study, bone biopsies and
evaluation of vascular calcifications were performed in fifty hemodialysis
patients. Cancellous bone volume, mineralized bone volume, osteoid volume,
activation frequency, bone formation rate/bone surface, osteoid thickness and
mineralization lag time were determined by histomorphometry. Vascular
calcifications were assessed by the simple vascular calcification score (SVCS) in
plain X-Ray of pelvis and hands and, for comparison, by the Agatston score in
Multi-Slice Computed Tomography (MSCT). RESULTS: SVCS>=3 was present in 20
patients (40%). Low and high bone turnover were present in 54% and 38% of
patients, respectively. Low bone volume was present in 20% of patients. In
multivariable analysis, higher age (p = 0.015) and longer hemodialysis duration
(p = 0.017) were associated with SVCS>=3. Contrary to cancellous bone volume, the
addition to this model of mineralized bone volume (OR = 0.863; 95%CI: 0.766,
0.971; p = 0.015), improved the performance of the model. For each increase of 1%
in mineralized bone volume there was a 13.7% decrease in the odds of having
SVCS>=3 (p = 0.015). An Agatston score>400 was observed in 80% of the patients
with a SVCS>=3 versus 4% of patients with a SVCS<3, (p<0.001). CONCLUSION: Higher
mineralized bone volume was associated with a lower plain X-ray vascular
calcification. This study corroborates the hypothesis of the existence of a link
between bone and vessel and reinforces the clinical utility of this simple and
inexpensive vascular calcification score in dialysis patients.
PMID- 28686737
TI - Simulated bat populations erode when exposed to climate change projections for
western North America.
AB - Recent research has demonstrated that temperature and precipitation conditions
correlate with successful reproduction in some insectivorous bat species that
live in arid and semiarid regions, and that hot and dry conditions correlate with
reduced lactation and reproductive output by females of some species. However,
the potential long-term impacts of climate-induced reproductive declines on bat
populations in western North America are not well understood. We combined results
from long-term field monitoring and experiments in our study area with
information on vital rates to develop stochastic age-structured population
dynamics models and analyzed how simulated fringed myotis (Myotis thysanodes)
populations changed under projected future climate conditions in our study area
near Boulder, Colorado (Boulder Models) and throughout western North America
(General Models). Each simulation consisted of an initial population of 2,000
females and an approximately stable age distribution at the beginning of the
simulation. We allowed each population to be influenced by the mean annual
temperature and annual precipitation for our study area and a generalized range
wide model projected through year 2086, for each of four carbon emission
scenarios (representative concentration pathways RCP2.6, RCP4.5, RCP6.0, RCP8.5).
Each population simulation was repeated 10,000 times. Of the 8 Boulder Model
simulations, 1 increased (+29.10%), 3 stayed approximately stable (+2.45%,
+0.05%, -0.03%), and 4 simulations decreased substantially (-44.10%, -44.70%,
44.95%, -78.85%). All General Model simulations for western North America
decreased by >90% (-93.75%, -96.70%, -96.70%, -98.75%). These results suggest
that a changing climate in western North America has the potential to quickly
erode some forest bat populations including species of conservation concern, such
as fringed myotis.
PMID- 28686738
TI - Correction: Assessment of Chronic Sublethal Effects of Imidacloprid on Honey Bee
Colony Health.
AB - [This corrects the article DOI: 10.1371/journal.pone.0118748.].
PMID- 28686739
TI - Defining and characterizing the critical transition state prior to the type 2
diabetes disease.
AB - BACKGROUND: Type 2 diabetes mellitus (T2DM), with increased risk of serious long
term complications, currently represents 8.3% of the adult population. We
hypothesized that a critical transition state prior to the new onset T2DM can be
revealed through the longitudinal electronic medical record (EMR) analysis.
METHOD: We applied the transition-based network entropy methodology which
previously identified a dynamic driver network (DDN) underlying the critical T2DM
transition at the tissue molecular biological level. To profile pre-disease
phenotypical changes that indicated a critical transition state, a cohort of
7,334 patients was assembled from the Maine State Health Information Exchange
(HIE). These patients all had their first confirmative diagnosis of T2DM between
January 1, 2013 and June 30, 2013. The cohort's EMRs from the 24 months preceding
their date of first T2DM diagnosis were extracted. RESULTS: Analysis of these
patients' pre-disease clinical history identified a dynamic driver network (DDN)
and an associated critical transition state six months prior to their first
confirmative T2DM state. CONCLUSIONS: This 6-month window before the disease
state provides an early warning of the impending T2DM, warranting an opportunity
to apply proactive interventions to prevent or delay the new onset of T2DM.
PMID- 28686741
TI - Correction: Functional restoration of the esophagus after peroral endoscopic
myotomy for achalasia.
AB - [This corrects the article DOI: 10.1371/journal.pone.0178414.].
PMID- 28686740
TI - CD4/CD8/Dendritic cell complexes in the spleen: CD8+ T cells can directly bind
CD4+ T cells and modulate their response.
AB - CD4+ T cell help to CD8+ T cell responses requires that CD4+ and CD8+ T cells
interact with the same antigen presenting dendritic cell (Ag+DC), but it remains
controversial whether helper signals are delivered indirectly through a licensed
DC and/or involve direct CD4+/CD8+ T cell contacts and/or the formation of
ternary complexes. We here describe the first in vivo imaging of the intact
spleen, aiming to evaluate the first interactions between antigen-specific CD4+,
CD8+ T cells and Ag+DCs. We show that in contrast to CD4+ T cells which form
transient contacts with Ag+DC, CD8+ T cells form immediate stable contacts and
activate the Ag+DC, acquire fragments of the DC membranes by trogocytosis,
leading to their acquisition of some of the DC properties. They express MHC class
II, and become able to present the specific Marilyn peptide to naive Marilyn CD4+
T cells, inducing their extensive division. In vivo, these CD8+ T cells form
direct stable contacts with motile naive CD4+ T cells, recruiting them to Ag+DC
binding and to the formation of ternary complexes, where CD4+ and CD8+ T cells
interact with the DC and with one another. The presence of CD8+ T cells during in
vivo immune responses leads to the early activation and up-regulation of multiple
functions by CD4+ T lymphocytes. Thus, while CD4+ T cell help is important to
CD8+ T cell responses, CD8+ T cells can interact directly with naive CD4+ T cells
impacting their recruitment and differentiation.
PMID- 28686742
TI - Determining the effect of different cooking methods on the nutritional
composition of salmon (Salmo salar) and chilean jack mackerel (Trachurus murphyi)
fillets.
AB - The effect of four cooking methods was evaluated for proximate composition, fatty
acid, calcium, iron, and zinc content in salmon and Chilean jack mackerel. The
moisture content of steamed salmon decreased (64.94%) compared to the control
(68.05%); a significant decrease was observed in Chilean jack mackerel in all the
treatments when compared to the control (75.37%). Protein content in both salmon
and Chilean jack mackerel significantly increased under the different treatments
while the most significant decrease in lipids was found in oven cooking and
canning for salmon and microwaving for Chilean jack mackerel. Ash concentration
in both salmon and Chilean jack mackerel did not reveal any significant
differences. Iron and calcium content only had significant changes in steaming
while zinc did not undergo any significant changes in the different treatments.
Finally, no drastic changes were observed in the fatty acid profile in both
salmon and Chilean jack mackerel.
PMID- 28686743
TI - The use of climate information to estimate future mortality from high ambient
temperature: A systematic literature review.
AB - BACKGROUND AND OBJECTIVES: Heat related mortality is of great concern for public
health, and estimates of future mortality under a warming climate are important
for planning of resources and possible adaptation measures. Papers providing
projections of future heat-related mortality were critically reviewed with a
focus on the use of climate model data. Some best practice guidelines are
proposed for future research. METHODS: The electronic databases Web of Science
and PubMed/Medline were searched for papers containing a quantitative estimate of
future heat-related mortality. The search was limited to papers published in
English in peer-reviewed journals up to the end of March 2017. Reference lists of
relevant papers and the citing literature were also examined. The wide range of
locations studied and climate data used prevented a meta-analysis. RESULTS: A
total of 608 articles were identified after removal of duplicate entries, of
which 63 were found to contain a quantitative estimate of future mortality from
hot days or heat waves. A wide range of mortality models and climate model data
have been used to estimate future mortality. Temperatures in the climate
simulations used in these studies were projected to increase. Consequently, all
the papers indicated that mortality from high temperatures would increase under a
warming climate. The spread in projections of future climate by models adds
substantial uncertainty to estimates of future heat-related mortality. However,
many studies either did not consider this source of uncertainty, or only used
results from a small number of climate models. Other studies showed that
uncertainty from changes in populations and demographics, and the methods for
adaptation to warmer temperatures were at least as important as climate model
uncertainty. Some inconsistencies in the use of climate data (for example, using
global mean temperature changes instead of changes for specific locations) and
interpretation of the effects on mortality were apparent. Some factors which have
not been considered when estimating future mortality are summarised. CONCLUSIONS:
Most studies have used climate data generated using scenarios with medium and
high emissions of greenhouse gases. More estimates of future mortality using
climate information from the mitigation scenario RCP2.6 are needed, as this
scenario is the only one under which the Paris Agreement to limit global warming
to 2 degrees C or less could be realised. Many of the methods used to combine
modelled data with local climate observations are simplistic. Quantile-based
methods might offer an improved approach, especially for temperatures at the ends
of the distributions. The modelling of adaptation to warmer temperatures in
mortality models is generally arbitrary and simplistic, and more research is
needed to better quantify adaptation. Only a small number of studies included
possible changes in population and demographics in their estimates of future
mortality, meaning many estimates of mortality could be biased low. Uncertainty
originating from establishing a mortality baseline, climate projections,
adaptation and population changes is important and should be considered when
estimating future mortality.
PMID- 28686744
TI - Should we treat patients with only one set of positive blood cultures for
extensively drug-resistant Acinetobacter baumannii the same as multiple sets?
AB - Acinetobacter species are not considered skin commensals and under-treatment is
an overriding concern when caring for critically-ill patients who are mostly at
risk of extensively drug-resistant Acinetobacter baumannii (XDRAB) infections.
Hence even a single blood culture yielding XDRAB will tend to prompt
intervention. However, field observations suggest that patients with single
positive blood cultures had milder disease and were more likely to be recruited
in interventional studies than those with multiple-positive blood cultures, yet
no distinction is made in current clinical or trial recruitment practices. To our
knowledge, this is the first study to compare the clinical characteristics and
outcomes of patients with single-positive versus multiple-positive blood cultures
for XDRAB. In this multicenter prospective cohort study of XDRAB bacteremic
patients from July 2010 to June 2015, only patients with at least two
simultaneously drawn blood cultures were included. The patients were classified
as having single-positive or multiple-positive blood cultures according to the
number of positive blood cultures yielding XDRAB. The primary end-point was the
28-day mortality. Of a total of 155 patients enrolled, 69 had a single-positive
and 86 had multiple-positive blood cultures. Leukopenia (37.2% vs. 16.2%; P =
0.004), thrombocytopenia (56.0% vs. 26.5%; P < 0.001), higher Pitt bacteremia
scores (6.6 vs. 5.5, P = 0.03) and higher 28-day mortality rates (70.9% vs.
43.5%; P = 0.001) distinguished patients with multiple-positive from those with
single-positive cultures. Multivariate logistic regression showed that multi
positivity independently predicted 28-day mortality (adjusted odds ratio, 2.34;
95% confidence interval (CI), 1.03-5.28; P = 0.04) and the Cox regression
confirmed that multi-positivity (adjusted hazard ratio, 1.80; 95% CI, 1.13-2.85;
P = 0.01) predicted rapid mortality. Patients with multiple versus single
positive blood cultures yielding XDRAB had greater morbidity and mortality.
Investigators and clinicians should be aware that the blood culture positivity
rate impacts outcomes of XDRAB bacteremia.
PMID- 28686745
TI - Protocols for the delivery of small molecules to the two-spotted spider mite,
Tetranychus urticae.
AB - The two-spotted spider mite, Tetranychus urticae, is a chelicerate herbivore with
an extremely wide host range and an extraordinary ability to develop pesticide
resistance. Due to its responsiveness to natural and synthetic xenobiotics, the
spider mite is becoming a prime pest herbivore model for studies of the evolution
of host range, plant-herbivore interactions and mechanisms of xenobiotic
resistance. The spider mite genome has been sequenced and its transcriptional
responses to developmental and various biotic and abiotic cues have been
documented. However, to identify biological and evolutionary roles of T. urticae
genes and proteins, it is necessary to develop methods for the efficient
manipulation of mite gene function or protein activity. Here, we describe
protocols developed for the delivery of small molecules into spider mites.
Starting with mite maintenance and the preparation of the experimental mite
populations of developmentally synchronized larvae and adults, we describe 3
methods for delivery of small molecules including artificial diet, leaf coating,
and soaking. The presented results define critical steps in these methods and
demonstrate that they can successfully deliver tracer dyes into mites. Described
protocols provide guidelines for high-throughput setups for delivery of
experimental compounds that could be used in reverse genetics platforms to
modulate gene expression or protein activity, or for screens focused on discovery
of new molecules for mite control. In addition, described protocols could be
adapted for other Tetranychidae and related species of economic importance such
as Varroa, dust and poultry mites.
PMID- 28686746
TI - Obstructive sleep apnea and objective short sleep duration are independently
associated with the risk of serum vitamin D deficiency.
AB - BACKGROUND: Studies demonstrate an association between vitamin D (25(OH)D)
deficiency and sleep disturbances, such as obstructive sleep apnea (OSA) and
short sleep duration. However, to date, no studies have concurrently and
objectively evaluated the effect of these factors on 25(OH)D. OBJECTIVES: To
evaluate whether OSA and objective short sleep duration are independently
associated with reduced 25(OH)D in an adult population sample. METHODS: A cross
sectional study included 657 individuals from the city of Sao Paulo, Brazil, as
part of the ERA project. Participants fulfilled questionnaires and underwent
clinical evaluation, polysomnography and blood sample collection for 25(OH)D
quantification. OSA was classified into three categories (mild, moderate and
severe). The risk of 25(OH)D deficiency was considered as levels<30 ng/mL. Short
sleep duration was defined as total sleep time<6 hours. RESULTS: The risk of
25(OH)D deficiency was observed in 59.5% of the sample, affecting more
individuals of the female gender, obese, with African American ethnicity, and
those that were smokers, sedentary and presented hypertension and diabetes. In
the final logistic model adjusted for age, gender, ethnicity, obesity, smoking,
hypertension, diabetes, sedentary lifestyle, seasonality and creatinine serum
levels, both OSA and short sleep duration showed significant independent
associations with the risk of 25(OH)D deficiency (moderate OSA: OR for 25(OH)D<30
= 2.21, 95% CI: 1.35-3.64, p<0.01; severe OSA: OR for 25(OH)D<30 = 1.78, 95% CI:
1.06-3.00, p = 0.03; short sleep duration: OR for 25(OH)D<30 = 1.61, 95% CI: 1.15
2.26, p = 0.01). After a subgroup analysis, similar results were observed only in
participants >=50 years. CONCLUSION: OSA and short sleep duration are
independently associated with the risk of 25(OH)D deficiency in an adult
population. Age-related changes in vitamin D metabolism and the frequency of
sleep disorders may be involved in these associations. Future studies exploring
whether 25(OH)D levels may modulate OSA and sleep curtailment-related outcomes
are needed.
PMID- 28686748
TI - Correction: Hepatitis C Virus Core Protein Down-Regulates p21Waf1/Cip1 and
Inhibits Curcumin-Induced Apoptosis through MicroRNA-345 Targeting in Human
Hepatoma Cells.
AB - [This corrects the article DOI: 10.1371/journal.pone.0061089.].
PMID- 28686750
TI - Magnification for the dermatologic surgeon.
AB - Ergonomic practice increases the productivity, quality, and longevity of the
dermatologic surgeon. When used properly, magnification devices can be ergonomic
and beneficial additions to the dermatologic surgeon's practice. Herein, we
review the available magnification options for the dermatologic surgeon and
evaluate the options based on cost, design, and functional advantages and
disadvantages. Magnification for the dermatologic surgeon may be a useful tool
for a healthier, more efficient, and higher-quality practice.
PMID- 28686747
TI - Functional analysis of the zebrafish ortholog of HMGCS1 reveals independent
functions for cholesterol and isoprenoids in craniofacial development.
AB - There are 8 different human syndromes caused by mutations in the cholesterol
synthesis pathway. A subset of these disorders such as Smith-Lemli-Opitz
disorder, are associated with facial dysmorphia. However, the molecular and
cellular mechanisms underlying such facial deficits are not fully understood,
primarily because of the diverse functions associated with the cholesterol
synthesis pathway. Recent evidence has demonstrated that mutation of the
zebrafish ortholog of HMGCR results in orofacial clefts. Here we sought to expand
upon these data, by deciphering the cholesterol dependent functions of the
cholesterol synthesis pathway from the cholesterol independent functions.
Moreover, we utilized loss of function analysis and pharmacological inhibition to
determine the extent of sonic hedgehog (Shh) signaling in animals with aberrant
cholesterol and/or isoprenoid synthesis. Our analysis confirmed that mutation of
hmgcs1, which encodes the first enzyme in the cholesterol synthesis pathway,
results in craniofacial abnormalities via defects in cranial neural crest cell
differentiation. Furthermore targeted pharmacological inhibition of the
cholesterol synthesis pathway revealed a novel function for isoprenoid synthesis
during vertebrate craniofacial development. Mutation of hmgcs1 had no effect on
Shh signaling at 2 and 3 days post fertilization (dpf), but did result in a
decrease in the expression of gli1, a known Shh target gene, at 4 dpf, after
morphological deficits in craniofacial development and chondrocyte
differentiation were observed in hmgcs1 mutants. These data raise the possibility
that deficiencies in cholesterol modulate chondrocyte differentiation by a
combination of Shh independent and Shh dependent mechanisms. Moreover, our
results describe a novel function for isoprenoids in facial development and
collectively suggest that cholesterol regulates craniofacial development through
versatile mechanisms.
PMID- 28686749
TI - Setting research priorities for maternal, newborn, child health and nutrition in
India by engaging experts from 256 indigenous institutions contributing over 4000
research ideas: a CHNRI exercise by ICMR and INCLEN.
AB - BACKGROUND: Health research in low- and middle- income countries (LMICs) is often
driven by donor priorities rather than by the needs of the countries where the
research takes place. This lack of alignment of donor's priorities with local
research need may be one of the reasons why countries fail to achieve set goals
for population health and nutrition. India has a high burden of morbidity and
mortality in women, children and infants. In order to look forward toward the
Sustainable Development Goals, the Indian Council of Medical Research (ICMR) and
the INCLEN Trust International (INCLEN) employed the Child Health and Nutrition
Research Initiative's (CHNRI) research priority setting method for maternal,
neonatal, child health and nutrition with the timeline of 2016-2025. The exercise
was the largest to-date use of the CHNRI methodology, both in terms of
participants and ideas generated and also expanded on the methodology. METHODS:
CHNRI is a crowdsourcing-based exercise that involves using the collective
intelligence of a group of stakeholders, usually researchers, to generate and
score research options against a set of criteria. This paper reports on a large
umbrella CHNRI that was divided into four theme-specific CHNRIs (maternal,
newborn, child health and nutrition). A National Steering Group oversaw the
exercise and four theme-specific Research Sub-Committees technically supported
finalizing the scoring criteria and refinement of research ideas for the
respective thematic areas. The exercise engaged participants from 256
institutions across India - 4003 research ideas were generated from 498 experts
which were consolidated into 373 research options (maternal health: 122; newborn
health: 56; child health: 101; nutrition: 94); 893 experts scored these against
five criteria (answerability, relevance, equity, innovation and out-of-box
thinking, investment on research). Relative weights to the criteria were assigned
by 79 members from the Larger Reference Group. Given India's diversity,
priorities were identified at national and three regional levels: (i) the
Empowered Action Group (EAG) and North-Eastern States; (ii) States and Union
territories in Northern India (including West Bengal); and (iii) States and Union
territories in Southern and Western parts of India. CONCLUSIONS: The exercise
leveraged the inherent flexibility of the CHNRI method in multiple ways. It
expanded on the CHNRI methodology enabling analyses for identification of
research priorities at national and regional levels. However, prioritization of
research options are only valuable if they are put to use, and we hope that
donors will take advantage of this prioritized list of research options.
PMID- 28686751
TI - Muckle-Wells syndrome in the setting of basal cell nevus syndrome.
AB - Muckle-Wells syndrome (MWS) is a rare disorder inherited in an autosomal-dominant
fashion that belongs to a group of hereditary periodic fever syndromes. It
specifically belongs to the cryopyrin-associated periodic syndromes (CAPSs) in
which there is a mutation in the NLRP3 (NLR family pyrin domain containing 3)
gene that leads to overproduction of IL-1beta, the source of the multisystem
inflammatory symptoms. Muckle-Wells syndrome is characterized by a recurrent
urticarial eruption that is associated with episodic fever, myalgia, arthralgia,
malaise, progressive sensorineural hearing loss, and amyloid nephropathy (the
most severe complication). Basal cell nevus syndrome (BCNS), or Gorlin syndrome,
is a rare, autosomal-dominant inherited genodermatosis linked to a mutation in
the PTCH1 (patched 1) gene and is characterized by a broad range of anomalies. We
report the case of a patient with MWS and BCNS in whom basal cell carcinoma (BCC)
treatment was complicated by symptoms of MWS.
PMID- 28686752
TI - Leukocytoclastic vasculitis resolution with topical dapsone.
AB - Leukocytoclastic vasculitis (LCV) is a disease characterized by inflammation of
small vessels presenting with petechiae and palpable purpura. Leukocytoclastic
vasculitis often spontaneously resolves within weeks and requires only
symptomatic treatment. Chronic or severe disease can require systemic treatment
with agents such as colchicine, dapsone, or corticosteroids, which are effective
but carry a risk for serious adverse events. These side effects and/or medical
contraindications preclude some patients from taking systemic medications for
LCV. We present a case of biopsy-proven LCV in a 60-year-old woman that resolved
after treatment with topical dapsone. Systemic dapsone is effective at treating
LCV but requires screening for glucose-6-phosphate dehydrogenase deficiency and
routine monitoring of blood counts, and its possible adverse effects include
neuropathy, blood dyscrasia, and hypersensitivity syndrome. Topical dapsone may
provide similar efficacy with far fewer adverse effects. Given this drug's
favorable side-effect profile compared to the currently available alternatives,
we believe it is a reasonable option in selected patients.
PMID- 28686753
TI - Narrowband UVB treatment increases serum 25-hydroxyvitamin D levels in patients
with chronic plaque psoriasis.
AB - The aim of this study was to investigate the effects of narrowband UVB (NB-UVB)
phototherapy on serum 25-hydroxyvitamin D (25[OH]D) levels and related parameters
in patients with psoriasis. Forty-nine participants with moderate to severe
plaque-type psoriasis were included in this study and were treated with NB-UVB
therapy 3 times weekly for 6 months or until psoriasis area and severity index
(PASI) 75 was achieved. Participants' serum 25(OH)D, calcium, phosphorus,
parathyroid hormone (PTH), and alkaline phosphatase (ALP) levels were measured at
baseline and completion of treatment, along with PASI scores. We observed that
the serum 25(OH)D levels increased after NB-UVB treatment, but the only
correlation that was found was the number of sessions of NB-UVB. There was no
relationship between patient age, Fitzpatrick skin type, PASI score, or maximum
NB-UVB dose and serum 25(OH)D levels.
PMID- 28686754
TI - Program for Maintenance of Certification by the American Board of Dermatology.
PMID- 28686755
TI - What's eating you? chiggers.
AB - Belonging to the Trombiculidae family of mites, chigger specifically refers to
the larval stage of the mite's life cycle when it is able to bite its host.
Although humans act as an accidental host, chiggers will latch on to the skin and
their feeding process leads to localized inflammation and irritation. In most
cases, these pruritic erythematous papules and papulovesicles are self-healing
within a couple weeks, so only symptomatic relief is required as necessary by
means of topical antipruritics, oral antihistamines, topical corticosteroids, or
an intralesional triamcinolone acetonide injection in severe instances. The best
practice, however, is to take preventative measures by completely covering one's
skin and applying products containing DEET to the skin and clothing when
traveling in infested areas.
PMID- 28686756
TI - Local anesthetics in cosmetic dermatology.
AB - Local anesthetics play an important role in cosmetic dermatology. Techniques
using topical and regional anesthesia provide numerous pain management options
for laser and injection treatments. In this article, we review strategies to
maximize patient comfort during cosmetic interventions.
PMID- 28686757
TI - Purpuric lesions of the scalp, axillae, and groin of an infant.
PMID- 28686758
TI - In vivo reflectance confocal microscopy.
AB - Reflectance confocal microscopy (RCM) has recently received Category I Current
Procedural Terminology (CPT) codes by the Centers for Medicare & Medicaid
Services for reimbursement comparable to a skin biopsy. In this article, we
present a review of RCM imaging and its benefits and limitations in diagnosis and
treatment planning. We also comment on guidelines for receiving reimbursement for
acquiring, reading, and interpreting RCM images.
PMID- 28686759
TI - BSA75, BSA90, and BSA100: new clinical tools for measuring improvement in
psoriasis.
PMID- 28686761
TI - Painful necrotic ulcer on the vulva.
PMID- 28686760
TI - Recurring yellowish papules and plaques on the back.
PMID- 28686762
TI - Ehlers-Danlos syndrome in a patient with Lynch syndrome: a hand-on-the-door
diagnosis.
PMID- 28686763
TI - Netherton syndrome in association with vitamin D deficiency.
PMID- 28686764
TI - Segmental vitiligo-like hypopigmentation associated with metastatic melanoma.
PMID- 28686765
TI - Cutaneous myoepithelial carcinoma with disseminated metastases.
AB - Primary cutaneous neoplasms of myoepithelial differentiation are uncommon.
Cutaneous myoepithelial carcinomas are rare. We report a case of cutaneous
myoepithelial carcinoma in a 47-year-old man with a history of end-stage renal
disease and renal transplant 19 years prior who presented to the hospital with a
3-month history of diffuse bone pain and an ulcerated scalp mass with multiple
satellite lesions. This case illustrates a rare instance of metastatic disease
from primary cutaneous myoepithelial carcinoma.
PMID- 28686767
TI - Five steps for delivering an effective and educational lecture.
AB - This article highlights 5 essential components of creating and effectively
delivering an educational lecture in the medical arena. Optimizing the
transmission of knowledge is ideal for fostering an atmosphere that is conducive
to all learners and helps physicians pursue their goal of lifelong learning.
PMID- 28686766
TI - Evaluation of patch test reactivities in patients with chronic idiopathic
urticaria.
AB - Chronic idiopathic urticaria (CIU) is one of the mysteries of dermatology. An
association between spontaneous CIU and contact allergy sensitization is
possible. In this study, we aimed to test the hypothesis that contact allergy
might play a role in disease in CIU patients. Furthermore, we examined if patch
testing should be routinely performed in patients with chronic urticaria (CU).
Ultimately, we concluded that patch testing should be included among the
diagnostic procedures for CU.
PMID- 28686769
TI - Metastatic Crohn disease: a review of dermatologic manifestations and treatment.
AB - It is estimated that almost half of patients affected with Crohn disease (CD)
experience a dermatologic manifestation of the condition. Metastatic CD (MCD) is
a rare dermatologic entity, with as few as 100 cases reported in the literature.
As such, MCD presents a clinical dilemma in diagnosis and management. The
etiology of MCD is not well defined; however, prevailing theories agree that the
underlying mechanism is an immunologic response to gut antigens. Diagnosis
requires a high index of suspicion and usually is made by exclusion of other
processes. Treatment success has been reported with the use of antibiotics,
immunosuppressants, and sometimes surgical treatment. We review the
etiology/epidemiology, diagnostic criteria, and treatment of this uncommon
condition.
PMID- 28686768
TI - Completeness of facial self-application of sunscreen in cosmetic surgery
patients.
AB - Previous studies have demonstrated incomplete sunscreen self-application to
various facial regions in cosmetic surgery patients, but there is no scientific
research on the completeness of facial and periocular sunscreen self-application
using ultraviolet (UV) photography for assessment. This prospective, cross
sectional, qualitative study aimed to assess completeness of facial application
of sunscreen in oculofacial surgery patients at the Duke Eye Center (Durham,
North Carolina). Forty-four participants were enrolled, and completeness of
facial sunscreen self-application was assessed using UV photography.
PMID- 28686770
TI - The Efficacy and Safety of Azelaic Acid 15% Foam in the Treatment of Truncal Acne
Vulgaris.
AB - INTRODUCTION: Truncal acne is often associated with facial acne, but there are
fewer options for an effective topical treatment on the trunk. Given the advent
of foam formulations with enhanced percutaneous absorption and convenient
application due to easy spreadability on skin, the previously held idea that
effective treatment of truncal acne requires oral treatment is challenged.
Azelaic acid cream has been previously approved for acne vulgaris, thus azelaic
acid foam may be a viable treatment option for truncal acne.
STUDY DESIGN:
A single-center, open label pilot study was conducted to investigate the efficacy
and safety of azelaic acid 15% foam as a treatment modality for moderate truncal
acne. Use for facial acne was also allowed and monitored during the study.
RESULTS: Twice-daily application of azelaic acid 15% foam to affected areas
resulted in a 1-grade reduction in truncal investigator global assessment (IGA)
scores in nearly all patients (16/18). Eight out of 18 patients (44%) were rated
as Clear or Almost Clear in the trunk by the end of the study. There were also
improvements in facial IGA scores; 9 of 18 patients (50%) exhibited a 1-grade
improvement in IGA scores and 11 of 18 were Clear or Almost Clear by the end of
the study. A significant reduction in lesion counts was found throughout the
study and the medication was well tolerated.
CONCUSION: Azelaic acid 15%
foam was effective in treating moderate truncal acne and facial acne in this
pilot study. Given the efficacy and convenience of the foam vehicle, azelaic acid
may be considered as a viable option for treatment of acne vulgaris, including on
the trunk. Further studies are suggested in a larger population of patients,
including adult females with acne.
J Drugs Dermatol. 2017;16(6):534
538.
.
PMID- 28686771
TI - Fixed Combination of Clindamycin Phosphate 1.2% and Benzoyl Peroxide 3.75%
Aqueous Gel: Long-Term Use in Adult Females With Moderate Acne Vulgaris.
AB - OBJECTIVE: To evaluate long-term efficacy and safety of a fixed combination
clindamycin phosphate 1.2% and benzoyl peroxide 3.75% (Clindamycin-BP 3.75%)
aqueous gel in adult female patients with moderate acne vulgaris.
METHODS:
Total of 20 patients, 25-63 years of age (mean [SD], 38 +/- 10) with moderate
acne (IGA=3) were treated with Clindamycin-BP 3.75% once-daily for 12 weeks.
Patients who experienced >=50% reduction in total lesion count continued
treatment for a further 12 weeks. Mean (SD) percent reduction in lesion counts
from baseline were assessed at week 4, 8, 12, 18, and 24. In addition, patients
who were 'clear' or 'almost clear' were reported at week 12 and 24. Cutaneous
tolerability (erythema, dryness, peeling, pruritus, and burning) and oiliness was
assessed at baseline and each study visit. Adverse events were assessed
throughout the study.
RESULTS: Clindamycin-BP 3.75% demonstrated
statistical significant improvement from baseline and between each visit. At week
12, mean percent reduction in inflammatory and noninflammatory lesion counts was
70.6% and 58.6%, respectively. Two patients failed to experience >=50% lesion
reduction by week 12. At week 24, mean percent reductions in inflammatory and
noninflammatory lesion counts were 93.8% and 90; 72% of patients were 'clear' or
'almost clear'. Overall the treatment was tolerable. There was one adverse event
(sinus infection) that was not treatment-related.
CONCLUSIONS: Clindamycin
BP 3.75% gel demonstrates continued improvement in symptoms of moderate acne over
24 weeks, with good tolerability, demonstrating a clinical benefit of continued
clindamycin-BP 3.75% gel as a maintenance therapy for acne in adult female
patients.
J Drugs Dermatol. 2017;16(6):543-546.
.
PMID- 28686772
TI - A Pilot, Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Safety
of IncobotulinumtoxinA Injections in the Treatment of Rosacea.
AB - BACKGROUND: Rosacea has a variable presentation. Whereas the pathophysiology
may differ, erythema, and flushing are the most consistent findings in all
patients.
OBJECTIVE: To evaluate the safety and efficacy of
incobotulinumtoxinA in reducing the severity of rosacea symptoms.
METHODS:
Nine subjects with erythematotelangiectactic or papulopustular rosacea were
randomized in 2 groups. Subjects in Group 1 (n=4) received up to a total of 20 U
of incobotulinumtoxinA in the affected area (across both cheeks). Subjects in
Group 2 (n=5) were injected with equal volumes of a saline solution. Rosacea
Clinical Scores and subject satisfaction were evaluated at baseline and at 1, 4,
12, and 16 weeks post-treatment. At week 16, both groups were injected with
incobotulinumtoxinA. Follow-up visits were performed at 1 and 4 weeks post
retreatment.
RESULTS: Patients in Group 1 exhibited reduction in the
primary features of rosacea within 4 weeks of treatment with incobotulinumtoxinA.
Consistent with this observation, patients in Group 2 (who had received the
placebo in the first arm without significant changes to their symptoms) exhibited
reductions in all of the primary and some of the secondary features upon
treatment with incobotulinumtoxinA.
CONCLUSIONS: IncobotulinumtoxinA may
be a safe and effective agent to reduce the severity of rosacea symptoms and
increase patient satisfaction.
J Drugs Dermatol. 2017;16(6):549
554.
.
PMID- 28686773
TI - Isotretinoin Monitoring Trends: A National Survey of Dermatologists.
AB - BACKGROUND: Isotretinoin is an effective treatment for nodulocystic acne.
Outside of required pregnancy testing, laboratory monitoring suggested by the
manufacturers is vague. Dermatologists, therefore, monitor a variety of tests
with variable frequency. Despite intense monitoring, the majority of patients do
not have gross laboratory abnormalities that warrant changes in management.
OBJECTIVE: To survey US dermatologists regarding laboratory monitoring
practices while prescribing isotretinoin.
METHODS: An online survey sent
via e-mail to members of the American Academy of Dermatology.
RESULTS:
12,396 surveys were sent with a response rate of ~19%. At baseline >60% of
responders check a CBC, LFTs, and a lipid panel. 74% check a monthly lipid panel
and LFTs, while 57% check a monthly CBC. 75% report stopping isotretinoin when
AST or ALT values reach 3 times normal; 89% report stopping at 4 times normal.
When triglycerides reach 4 times normal, 72% stop the medication.
CONCLUSIONS: There is no consensus on isotretinoin monitoring tests and
frequency, though the majority of dermatologists surveyed monitor a lipid panel
and LFTs.
J Drugs Dermatol. 2017;16(6):557-564.
.
PMID- 28686774
TI - Prospective Study of Pathogenesis of Atrophic Acne Scars and Role of Macular
Erythema.
AB - BACKGROUND: There are few studies on the natural history of acne lesions
including the antecedents of atrophic scars.
STUDY DESIGN: Prospective
study of relationship between primary (papules, pustules, comedones) and
secondary lesions (atrophic scars, macular erythema, and hyperpigmentation) over
6 months. Subjects (n=32) had moderate facial acne including 10 or more atrophic
acne scars and were their own control via randomized split-face design. Lesions
were mapped 2x/week for 2 months and every 2 weeks thereafter until month 6 to
track pathogenic progression.
RESULTS: Clinical assessment showed acne
scars continuously forming throughout the 6-month study period. While the
majority (66.2%) of these scars did not resolve by study endpoint, the remainder
were transient. The likelihood of a scar developing from a primary acne lesion
was 5.7%, and almost all scars arose from erythematous macules or
hyperpigmentation (83%) and some (16%) developed directly from papules and
pustules. Duration of papules was a key factor in the risk of scarring. The
majority (81.7%) of the scars remaining at 6 months were still present at 2-year
follow-up.
CONCLUSIONS: Atrophic acne scars continuously form, some
resolve, and evolve primarily from inflammatory and post-inflammatory lesions.
Clinicians should closely monitor patients with macular erythema for
scarring.
J Drugs Dermatol. 2017;16(6):566-572.
.
PMID- 28686775
TI - Adapalene/Benzoyl Peroxide Gel 0.3%/2.5%: A Safe and Effective Acne Therapy in
All Skin Phototypes.
AB - BACKGROUND: Acne affects individuals of all races and ethnicities; however,
lighter and darker skin phototypes face different treatment challenges that may
affect treatment response and tolerability. This analysis investigated possible
differences in the efficacy and safety of the fixed dose combination of 0.3%
adapalene with 2.5% benzoyl peroxide (A/BPO gel 0.3%/2.5%) in subjects with
Fitzpatrick Skin Types (FST) I-VI.
METHODS: This was a post-hoc analysis
of a Phase 3, multicenter, randomized, double-blind, parallel-group study of
moderate to severe acne in subjects with FST I-VI. Subjects received A/BPO gel
0.3%/2.5%, A/BPO gel 0.1%/2.5% (benchmark), or vehicle, once daily for 12 weeks.
Efficacy measurements included success rate (IGA of Clear or Almost Clear),
change in inflammatory and noninflammatory lesions from baseline to week 12,
safety, and tolerability. The intent to treat (ITT) and safety populations were
analyzed. Demographics and disposition were analyzed with descriptive statistics;
categorical variables by frequency and percentage; and continuous variables with
means, medians, minimum, maximum, and standard deviations.
RESULTS: The
A/BPO gel 0.3%/2.5% treatment group included 128 subjects with FST I-III, and 89
subjects with FST IV-VI. At week 12, A/BPO gel 0.3%/2.5% was safe, tolerable, and
significantly superior to vehicle for all FST and severity groups in inflammatory
and noninflammatory lesion reduction (P less than equal to .05). Compared to
baseline, 32% of subjects with FST I-III were clear or almost clear, compared to
7% in the vehicle group (P=.001). In FST IV-VI, 28% of subjects were clear or
almost clear, compared to 15% for vehicle (P=NS). In all treatment groups and
skin phototypes, week 12 tolerability scores were similar to baseline scores, and
tolerability scores for most subjects of all skin phototypes were "none" or
"mild" for all measures.
SUMMARY: We report that the fixed dose
combination of A/BPO gel 0.3%/2.5% is efficacious and safe in patients with FST I
VI with moderate and severe inflammatory acne.
Clinicaltrials.gov
registry: NCT01880320
J Drugs Dermatol. 2017;16(6):574-581.
.
PMID- 28686776
TI - Adapalene/Benzoyl Peroxide Gel 0.3%/2.5%: Effective Acne Therapy Regardless of
Age or Gender.
AB - BACKGROUND: Acne vulgaris affects a diverse group of people, and there is an
increasingly wide variety of acne treatments. Because of the many options,
clinicians have a better ability to individualize treatment; however, achieving
optimal results relies on understanding how various agents perform in specific
population segments. Fixed-combination adapalene plus benzoyl peroxide (A/BPO) is
a first-line recommended acne therapy and is available in two adapalene
concentrations (0.1% and 0.3%) combined with BPO 2.5%. This analysis investigated
whether gender and age have an impact on either the efficacy or safety of topical
A/BPO 0.3%.
METHODS: A post-hoc subanalysis was performed on data from a
multicenter, randomized, double-blind, parallelgroup, 12-week study of A/BPO gel
0.3%/2.5% or vehicle gel in subjects >= 12 years old with moderate to severe acne
vulgaris (Investigator global assessment [IGA] of 3 or 4). Efficacy measurements
included achievement of an IGA of clear (0) or almost clear (1), and change in
lesion counts from baseline to week 12. Safety measures included adverse events
and cutaneous tolerability. The intent to treat (ITT) and safety populations were
analyzed.
RESULTS: The A/BPO gel 0.3%/2.5% treatment group included 217
subjects. Among the subjects, 111 were 12-17 years old and 106 were >= 18 years
old; 104 were male and 113 were female. A/BPO 0.3%/2.5% was safe, tolerable, and
significantly superior to vehicle in success rates (IGA 0 or 1) and reduction of
inflammatory/noninflammatory lesions (P<=0.05) across both age groups and
genders.
CONCLUSIONS: A/BPO 0.3%/2.5% treatment achieved success and was
equally effective and safe in younger vs older subjects and in males vs females.
These results support the use of A/BPO 0.3%/2.5% in all subjects 12 and
older.
Clinicaltrials.gov registry: (NCT01880320)
J Drugs
Dermatol. 2017;16(6):582-589.
.
PMID- 28686777
TI - Treatment Response With Once-Daily Topical Dapsone Gel, 7.5% for Acne Vulgaris:
Subgroup Analysis of Pooled Data from Two Randomized, Double-Blind Stu.
AB - BACKGROUND: Acne vulgaris has varying physical and psychological effects in
men and women of different ages, races, and ethnicities.
OBJECTIVE: This
analysis assessed the relationship of age, sex, and race to treatment response
with once-daily topical dapsone gel, 7.5%.
METHODS: We conducted a pooled
subgroup analysis of 2 randomized, double-blind, vehicle-controlled clinical
trials conducted in the US and Canada. The studies included patients with 20 to
50 inflammatory and 30 to 100 noninflammatory facial lesions, and a Global Acne
Assessment Score (GAAS) of 3 (moderate). Pooled data (N=4340) were analyzed by
age (12-17 and >=18 years), sex, and race (Caucasian and non-Caucasian) for GAAS
success (score of 0 [none] or 1 [minimal]) and mean percent change from baseline
in inflammatory, noninflammatory, and total lesion counts. The impact of age and
sex on treatment response was examined using multivariate analysis. Adverse
events were analyzed by subgroups.
RESULTS: Treatment responses with
dapsone gel, 7.5% were greater overall and for all subgroups versus vehicle. GAAS
success rates and mean decrease in all lesion counts with dapsone gel, 7.5% were
greater in older (aged >=18 years) versus younger patients, and for females
versus males. Treatment response with dapsone gel, 7.5% in racial subgroups was
similar. Multivariate analysis showed statistical significance for age group and
sex as predictors of GAAS success (P less than equal to .005) and reduction in
lesion counts (P less than equal to .025). Adverse events were similar across
subgroups.
CONCLUSIONS: Older age (>=18 years) and female sex were
predictors of treatment response. These subgroups tended to have greater acne
improvement in subgroup comparisons. Caucasian and non-Caucasian patients had
similar responses. The safety profile of dapsone gel, 7.5% was similar across
subgroups.
J Drugs Dermatol. 2017;16(6):591-598.
.
PMID- 28686778
TI - A Randomized Controlled Study of a Novel Botanical Acne Spot Treatment.
AB - OBJECTIVE: The study evaluated the tolerability and efficacy of a new
presented treatment for acne. The product is an OTC topical gel consisting of 2%
SA, which is also enriched in botanicals that have been shown to have anti
inflammatory properties.
DESIGN: The study was designed as a single-site,
randomized, investigator-blinded, split-face 10-day study.
SETTING:
Subjects enrolled with a minimum of 2 inflammatory papular acne lesions and 2 non
inflammatory open or closed comedones on both sides of the face in symmetrical
locations, to the greatest degree possible. One side of each subject's face was
randomly selected to receive the study treatment product.
PARTICIPANTS: 25
subjects, 15 female and 10 males, ages 12 to 43 years, suffering from mild to
moderate acne.
Measurements: Study duration was 10 days, with study visits
occurring at baseline (day 0), day 1, day 2, day 3, day 7, and day 10. Subjects
underwent investigator facial evaluation and lesion assessment by dermatologist
at each of the visit days. For the inflammatory lesions, the assessed parameters
were erythema, elevation, induration, and overall impression. The assessed non
inflammatory parameters were elevation and overall impression.
Results:
The observed difference between the treatment and the control group increased
between day 1 and day 2 and reached an average of 15% to 20% with small varieties
between the parameters and stayed similar across the remaining visits.
Statistically significance (P less than 0.005) was achieved for all inflammatory
and non-inflammatory tested parameters.
Conclusion: This study was
performed to determine the safety, efficacy, and ease of use of a botanical acne
treatment gel in providing a reduction in inflammatory acne lesion erythema,
elevation, and induration. Erythema and elevation were the most influential
parameters in inflammatory lesion with improvement noted after 2 days of
application.
J Drugs Dermatol. 2017;16(6):599-603.
.
PMID- 28686779
TI - Efficacy and Tolerability of a Cosmetic Skin Care Product With Trans-4-t
butylcyclohexanol and Licochalcone A in Subjects With Sensitive Skin Prone to
Redness and Rosacea.
AB - BACKGROUND: Sensitive skin and rosacea are skin conditions, which may affect
the quality of life of the patients considerably. In vitro and in vivo data
indicated that the combination of trans-t-butylcyclohexanol and licochalcone A is
an effective combination for alleviating the increased sensitivity of rosacea
subtype I.
OBJECTIVE: Objective of this open dermocosmetic study was to
investigate the efficacy and tolerability of a skin care product containing the
anti-inflammatory licochalcone A and the TRPV1 antagonist trans-t
butylcyclohexanol in subjects with sensitive skin prone to redness and
rosacea.
METHODS: 1221 subjects with sensitive skin and rosacea stage 0-II
applied the test product twice daily for 4 weeks. Clinical assessment of
sensitive skin and rosacea symptoms were performed at baseline and after 4 weeks.
Additionally, at treatment end the test subjects filled a self-assessment
questionnaire.
RESULTS: After 4 weeks of application, both, clinical and
subjective assessment have shown improvement of all symptoms of sensitive skin
and rosacea in a significant number of subjects (P less than 0.001). The test
product was efficacious and very well tolerated also when used in conjunction
with pharmacological treatments of the skin condition under scrutiny.
Conclusions: The study confirmed the good tolerability and efficacy of the
skin care product in the management of sensitive skin prone to redness and
rosacea when used alone or in combination with other therapies.
J
Drugs Dermatol. 2017;16(6):605-611.
.
PMID- 28686780
TI - A Survey Assessment of US Dermatologists' Perception of Biosimilars.
AB - BACKGROUND: Biologics have transformed the treatment of psoriasis and
psoriatic arthritis, but at a significant cost to payers and patients. The
introduction of biosimilars into the US market could reduce costs while
increasing access to biologic medications.
OBJECTIVE: We sought to
identify gaps in biosimilar knowledge and perception among US dermatologists.
METHODS: An online survey was sent to dermatologists from January to April
2015.
RESULTS: Ninety-seven US dermatologists responded, of which 84%
state they prescribe biologics in their practice. Only 37% of dermatologists were
aware that a biosimilar is highly similar to a US-licensed reference biological
product, 26% incorrectly described a biosimilar as a "generic" of a known
biologic, and 10% of dermatologists stated they did not know the definition. Most
dermatologists (88%) believe that substitutions from biologics to biosimilars
will be made by pharmacists without consulting the physician. A total of 37% of
dermatologists believed that a biosimilar with the same name as a biologic
suggested they are "structurally identical." Only 25% said they would likely
prescribe biosimilars to their patients, while 38% stated they would try using
them on a very select, small group of patients before trying it on a majority of
their patients.
LIMITATIONS: Limitations include small sample size and non
responder bias.
CONCLUSION: A biosimilars knowledge gap exists amongst
dermatologists, suggesting the need for more educational initiatives.
J Drugs Dermatol. 2017;16(6):612-615.
.
PMID- 28686781
TI - Facial Identity and Self-Perception: An Examination of Psychosocial Outcomes in
Cosmetic Surgery Patients.
AB - The psychosocial health of patients undergoing cosmetic procedures has often
been linked to a host of pre-existing conditions, including the type of procedure
being performed. Age, gender, and the psychological state of the patients also
contribute to the perceived outcome. Specifically, the presence or absence of
Body Dysmorphic Disorder (BDD) has been identified as an independent marker for
unhappiness following cosmetic procedures.1 However, no study has, to our
knowledge, identified a more precise indicator that is associated with higher
rates of patient dissatisfaction from cosmetic procedure. This review identifies
facial identity and self-perception as potential identifiers of future patient
dissatisfaction with cosmetic procedures. Specifically, we believe that patients
with a realistic facial identity and self-perception are more likely to be
satisfied than those whose self-perceptions are distorted. Patients undergoing
restorative procedures, including blepharoplasty, rhytidectomy, and liposuction,
are more likely to have an increased outcome favorability rating than those
undergoing type change procedures, such as rhinoplasty and breast augmentation.
Age, which typically is an independent variable for satisfaction, tends to be
associated with increased favorability ratings following cosmetic procedures.
Female gender is a second variable associated with higher satisfaction. The
authors believe that negative facial identity and self-perception are risk
factors for patient dissatisfaction with cosmetic procedural outcomes. Based on
this assumption, clinicians may want to focus on the face as a particular area of
psychosocial concern.
J Drugs Dermatol. 2017;16(6):617-620.
.
PMID- 28686782
TI - Eruptive Milia Within a Tattoo: A Case Report and Review of the Literature.
AB - Of the many tattoo reactions the most common are allergic, granulomatous,
lichenoid, photosensitive, pseudolymphomatous, and infectious. Eruptive milia are
a rare complication with only three prior reports in the English literature. A 19
year-old African American female presented with tiny, white papules confined
within the margins of a tattoo. She denied trauma or associated symptoms at the
site. Biopsy demonstrated deposits of black granular material within the dermis
and a small infundibular cyst; a diagnosis of eruptive milia within tattoo was
made. The milia responded to treatment with urea 40% cream and tretinoin 0.1%
cream. Given its rarity, it is important to recognize the presentation of this
disorder as other tattoo reactions require more aggressive management. While
further research is necessary to determine the exact pathogenesis of this
condition, the authors propose a mechanism along with a review of the literature
to discuss management.
J Drugs Dermatol. 2017;16(6):621-624.
.
PMID- 28686783
TI - Schnitzler Syndrome With Delirium and Vertigo: The Utility of Neurologic
Manifestations in Diagnosis.
AB - Schnitzler syndrome (SS) is an autoinflammatory dermatosis that often goes
undiagnosed for 5-6 years. Patients typically carry a diagnosis of urticaria;
however, their cutaneous symptoms fail to respond to typical urticaria therapies
and lack symptoms such as pruritus. Additionally, patients with SS may see
multiple providers for nonspecific complaints of fever, lymphadenopathy,
arthralgias, and bone pain. A correct diagnosis is paramount, as close to 20% of
patients may develop a lymphoproliferative disorder and appropriate treatment may
ameliorate all symptoms.1 We report 2 cases of SS misdiagnosed as urticaria for
years in order to illuminate diagnostic pearls, histopathological findings, and
treatment modalities. Additionally, we highlight the importance of neurologic
disturbances in this rare but important differential diagnosis of urticaria.
J Drugs Dermatol. 2017;16(6):625-627.
.
PMID- 28686784
TI - Aging Gracefully.
AB - At the Annual Meeting of the American Academy of Dermatology in 2016, I directed
the symposium entitled 'Aging Gracefully' for the second time. The symposium's
primary learning objective was to give the audience a framework for managing
aesthetic patients. In the last decade, there has been a significant increase in
the options for and availability of noninvasive and minimally invasive
rejuvenation. With that has been an associated surge in interest by physicians
and patients. And, as the number of procedures across the globe increases, so too
do the number of aesthetically poor outcomes. Most come from practitioners doing
paint-by-numbers treatment. As experts in skin biology and treatment,
dermatologists should practice the highest-level cosmetic as well as general
dermatology. The faculty presented information to aid practitioners how best to
approach patients and formulate a cosmetic plan. The faculty discussed important
considerations based on patient gender, age, and skin type. Updated information
on the science of cosmeceuticals and the benefits of early noninvasive
intervention was presented as were next generation devices and alternatives to
standard therapies. The faculty have kindly condensed their AAD presentations for
this supplement. I thank L'Oreal and the Journal of Drugs in Dermatology for
giving us the opportunity to present this information to a wider audience in this
e-supplement.Heidi A. Waldorf MDDirector of Laser & Cosmetic Dermatology, The
Mount Sinai Hospital, New York, NYIcahn School of Medicine of Mount Sinai, New
York, NYWaldorf Dermatology Aesthetics, Nanuet, NY
PMID- 28686786
TI - Disparities in the Use of Diabetes Screening in Appalachia.
AB - PURPOSE: The Appalachian region presents disproportionately high rates of chronic
disease compared to the rest of the United States. Early diagnosis of diabetes
through screening is an important step in reducing diabetes complications. This
study examines disparities in the use of diabetes screening in Appalachia.
METHODS: We analyzed 2009 and 2010 Behavioral Risk Factor Surveillance System
data for 96,111 adults aged >=45 years from 11 Appalachian states. Based on
economic status, Appalachian counties were grouped into distressed (least
affluent), at-risk, transitional, and competitive (most affluent). Logistic
regression analyses were used to estimate the statistical significance and effect
size of factors associated with diabetes screening. RESULTS: Competitive counties
had the highest rate of diabetes screening (65.4%). At-risk counties had the
lowest rate (60.3%), about 7.8% lower compared to competitive counties (P <
.001). After adjusting for socioeconomic factors, differences in screening rates
between county economic levels in Appalachia were not statistically significant.
Among respondents >=65 years, at-risk counties had an 8.1% lower screening rate
compared to competitive counties; this difference was not adequately explained by
differences in socioeconomic factors. Screening rates in distressed and
transitional counties were not significantly different from competitive counties
in unadjusted or adjusted models. CONCLUSIONS: At-risk counties had significantly
lower screening rates than competitive counties. They should receive more policy
attention similar to that received by distressed counties. Social policies that
improve socioeconomic status and educational attainment, and health policies that
reduce barriers to access to care may reduce disparities in diabetes screening
rates in the less affluent Appalachian counties.
PMID- 28686785
TI - Liquid crystal phantom for validation of microscopic diffusion anisotropy
measurements on clinical MRI systems.
AB - PURPOSE: To develop a phantom for validating MRI pulse sequences and data
processing methods to quantify microscopic diffusion anisotropy in the human
brain. METHODS: Using a liquid crystal consisting of water, detergent, and
hydrocarbon, we designed a 0.5-L spherical phantom showing the theoretically
highest possible degree of microscopic anisotropy. Data were acquired on the
Connectome scanner using echo-planar imaging signal readout and diffusion
encoding with axisymmetric b-tensors of varying magnitude, anisotropy, and
orientation. The mean diffusivity, fractional anisotropy (FA), and microscopic FA
(uFA) parameters were estimated. RESULTS: The phantom was observed to have values
of mean diffusivity similar to brain tissue, and relaxation times compatible with
echo-planar imaging echo times on the order of 100 ms. The estimated values of
uFA were at the theoretical maximum of 1.0, whereas the values of FA spanned the
interval from 0.0 to 0.8 as a result of varying orientational order of the
anisotropic domains within each voxel. CONCLUSIONS: The proposed phantom can be
manufactured by mixing three widely available chemicals in volumes comparable to
a human head. The acquired data are in excellent agreement with theoretical
predictions, showing that the phantom is ideal for validating methods for
measuring microscopic diffusion anisotropy on clinical MRI systems. Magn Reson
Med 79:1817-1828, 2018. (c) 2017 The Authors Magnetic Resonance in Medicine
published by Wiley Periodicals, Inc. on behalf of International Society for
Magnetic Resonance in Medicine. This is an open access article under the terms of
the Creative Commons Attribution-NonCommercial License, which permits use,
distribution and reproduction in any medium, provided the original work is
properly cited and is not used for commercial purposes.
PMID- 28686787
TI - Barriers and Facilitators of Colorectal Cancer Screening for Patients of Rural
Accountable Care Organization Clinics: A Multilevel Analysis.
AB - PURPOSE: This study examines multilevel factors related to colorectal cancer
(CRC) screening in a rural Accountable Care Organization (ACO) setting. METHODS:
The study used electronic medical record data from 8 rural ACO clinics in
Nebraska. The final sample included 15,866 average-risk patients aged 50-75 years
who visited participating clinics at least once from June 2014 to May 2015.
Logistic regression was conducted to examine simultaneous effects of patient,
provider, and county characteristics on CRC screening after accounting for
provider-county-level correlation using a generalized estimating equations
method. FINDINGS: The results indicated that patients aged 65 years and older,
non-Hispanic white, whose preferred language was English, who had insurance, who
had a wellness visit in the past year, and who had chronic conditions were more
likely to be up-to-date on CRC screening. Patients were also more likely to be up
to-date when their primary care provider was a female medical doctor who was
aware of clinic CRC screening protocols or who manually checked patient CRC
screening status during the patient visit. Patients in a county with no
gastroenterologist, a high poverty rate, and low insurance coverage were less
likely to be up-to-date on CRC screening. CONCLUSIONS: A variety of patient,
provider, and county characteristics were associated with CRC screening.
Effective strategies to promote CRC screening should address multilevel factors,
including: targeting patients with identified individual barriers, modifying
physician and clinical practices, and focusing on communities with low
socioeconomic status or low levels of medical resources.
PMID- 28686788
TI - Influence of physiological noise on accelerated 2D and 3D resting state
functional MRI data at 7 T.
AB - PURPOSE: Physiological noise often dominates the blood-oxygen level-dependent
(BOLD) signal fluctuations in high-field functional MRI (fMRI) data. Therefore,
to optimize fMRI protocols, it becomes crucial to investigate how physiological
signal fluctuations impact various acquisition and reconstruction schemes at
different acquisition speeds. In particular, further differences can arise
between 2D and 3D fMRI acquisitions due to different encoding strategies, thereby
impacting fMRI sensitivity in potentially significant ways. METHODS: The amount
of physiological noise to be removed from the BOLD fMRI signal acquired at 7 T
was quantified for different sampling rates (repetition time from 3300 to 350 ms,
acceleration 1 to 8) and techniques dedicated to fast fMRI (simultaneous
multislice echo planar imaging [EPI] and 3D EPI). Resting state fMRI (rsfMRI)
performances were evaluated using temporal signal-to-noise ratio (tSNR) and
network characterization based on seed correlation and independent component
analysis. RESULTS: Overall, acceleration enhanced tSNR and rsfMRI metrics. 3D EPI
benefited the most from physiological noise removal at long repetition times.
Differences between 2D and 3D encoding strategies disappeared at high
acceleration factors (6- to 8-fold). CONCLUSION: After physiological noise
correction, 2D- and 3D-accelerated sequences provide similar performances at high
fields, both in terms of tSNR and resting state network identification and
characterization. Magn Reson Med 78:888-896, 2017. (c) 2017 International Society
for Magnetic Resonance in Medicine.
PMID- 28686789
TI - Tris(2,4,6-trifluorophenyl)borane: An Efficient Hydroboration Catalyst.
AB - The metal-free catalyst tris(2,4,6-trifluorophenyl)borane has demonstrated its
extensive applications in the 1,2-hydroboration of numerous unsaturated reagents,
namely alkynes, aldehydes and imines, consisting of a wide array of electron
withdrawing and donating functionalities. A range of over 50 borylated products
are reported, with many reactions proceeding with low catalyst loading under
ambient conditions. These pinacol boronate esters, in the case of aldehydes and
imines, can be readily hydrolyzed to leave the respective alcohol and amine,
whereas alkynyl substrates result in vinyl boranes. This is of great synthetic
use to the organic chemist.
PMID- 28686790
TI - Adipose stem cells enhance myoblast proliferation via acetylcholine and
extracellular signal-regulated kinase 1/2 signaling.
AB - INTRODUCTION: In this study we investigated the interaction between adipose
tissue-derived stem cells (ASCs) and myoblasts in co-culture experiments.
METHODS: Specific inductive media were used to differentiate ASCs in vitro into a
Schwann cell-like phenotype (differentiated adipose tissue-derived stem cells, or
dASCs) and, subsequently, the expression of acetylcholine (ACh)-related machinery
was determined. In addition, the expression of muscarinic ACh receptors was
examined in denervated rat gastrocnemius muscles. RESULTS: In contrast to
undifferentiated ASCs, dASCs expressed more choline acetyltransferase and
vesicular acetylcholine transporter. When co-cultured with myoblasts, dASCs
enhanced the proliferation rate, as did ACh administration alone. Western
blotting and pharmacological inhibitor studies showed that phosphorylated
extracellular signal-regulated kinase 1/2 signaling mediated these effects. In
addition, denervated muscle showed higher expression of muscarinic ACh receptors
than control muscle. DISCUSSION: Our findings suggest that dASCs promote
proliferation of myoblasts through paracrine secretion of ACh, which could
explain some of their regenerative capacity in vivo. Muscle Nerve 57: 305-311,
2018.
PMID- 28686791
TI - Adherence and stress in a population of inner-city children with asthma.
PMID- 28686792
TI - IgG subclass deficiencies in children: Facts and fiction.
AB - The chance to analyse the four IgG subclasses arose with the publication of Terry
and Fahey1 . Since then, a lot of new information on the role of subclasses and
their deficiency states in humans has been obtained. This review tries to analyse
critically our current knowledge of subclass deficiencies in children.
PMID- 28686793
TI - Learning and memory effects of neonatal methamphetamine exposure in rats: Role of
reactive oxygen species and age at assessment.
AB - In utero methamphetamine (MA) exposure leads to a range of adverse effects, such
as decreased attention, reduced working-memory capability, behavioral
dysregulation, and spatial memory impairments in exposed children. In the current
experiment, preweaning Sprague-Dawley rats-as a model of third trimester human
exposure-were administered the spin trapping agent, N-tert-butyl-alpha
phenylnitrone (PBN), daily prior to MA. Rats were given 0 (SAL) or 40 mg/kg PBN
prior to each MA dose (10 mg/kg, 4* per day) from postnatal day (P) 6-15.
Littermates underwent Cincinnati water maze, Morris water maze, and radial water
maze assessment beginning on P30 (males) or P60 (females). Males were also tested
for conditioned contextual and cued freezing, while females were trained in
passive avoidance. Findings show that, regardless of age/sex, neonatal MA induced
deficits in all tests, except passive avoidance. PBN did not ameliorate these
effects, but had a few minor effects. Taken together, MA induced learning
deficits emerge early and persist, but the mechanism remains unknown.
PMID- 28686795
TI - Reply.
PMID- 28686794
TI - Simultaneous quantitation of meperidine, normeperidine, tramadol, propoxyphene
and norpropoxyphene in human plasma using solid-phase extraction and gas
chromatography/mass spectrometry: Method validation and application to
cardiovascular safety of therapeutic doses.
AB - RATIONALE: Several opioid analgesics have been related to the prolongation of
cardiac repolarization, a condition which can be fatal. In order to establish a
correct estimation of the risk/benefit balance of therapeutic doses of
meperidine, normeperidine, tramadol, propoxyphene and norpropoxyphene, it was
necessary to develop an analytical method to determinate plasma concentrations of
these opioids. METHODS: Here we describe a method which incorporates strong
alkaline treatment to obtain norpropoxyphene amide followed by a one-elution step
solid-phase extraction, and without further derivatization. Separation and
quantification were achieved by gas chromatography/electron ionization mass
spectrometry (GC/EI-MS) in selected-ion monitoring mode. Quantification was
performed with 500 MUL of plasma by the addition of deuterated analogues as
internal standards. RESULTS: The proposed method has been validated in the
linearity range of 25-1000 ng/mL for all the analytes, with correlation
coefficients higher than 0.990. The lower limit of quantification was 25 ng/mL.
The intra- and inter-day precision, calculated in terms of relative standard
deviation, were 2.0-12.0% and 6.0-15.0%, respectively. The accuracy, in terms of
relative error, was within a +/- 10% interval. The absolute recovery and
extraction efficiency ranged from 81.0 to 111.0% and 81.0 to 105.0%,
respectively. CONCLUSIONS: A GC/MS method for the rapid and simultaneous
determination of meperidine, normeperidine, tramadol, propoxyphene and
norpropoxyphene in human plasma was developed, optimized and validated. This
procedure was shown to be sensitive and specific using small specimen amounts,
suitable for application in routine analysis for forensic purposes and
therapeutic monitoring. To our knowledge, this is the first full validation of
the simultaneous determination of these opioids and their metabolites in plasma
samples.
PMID- 28686796
TI - QUESP and QUEST revisited - fast and accurate quantitative CEST experiments.
AB - PURPOSE: Chemical exchange saturation transfer (CEST) NMR or MRI experiments
allow detection of low concentrated molecules with enhanced sensitivity via their
proton exchange with the abundant water pool. Be it endogenous metabolites or
exogenous contrast agents, an exact quantification of the actual exchange rate is
required to design optimal pulse sequences and/or specific sensitive agents.
METHODS: Refined analytical expressions allow deeper insight and improvement of
accuracy for common quantification techniques. The accuracy of standard
quantification methodologies, such as quantification of exchange rate using
varying saturation power or varying saturation time, is improved especially for
the case of nonequilibrium initial conditions and weak labeling conditions,
meaning the saturation amplitude is smaller than the exchange rate (gammaB1 <
k). RESULTS: The improved analytical 'quantification of exchange rate using
varying saturation power/time' (QUESP/QUEST) equations allow for more accurate
exchange rate determination, and provide clear insights on the general principles
to execute the experiments and to perform numerical evaluation. The proposed
methodology was evaluated on the large-shift regime of paramagnetic chemical
exchange-saturation-transfer agents using simulated data and data of the
paramagnetic Eu(III) complex of DOTA-tetraglycineamide. CONCLUSIONS: The refined
formulas yield improved exchange rate estimation. General convergence intervals
of the methods that would apply for smaller shift agents are also discussed. Magn
Reson Med 79:1708-1721, 2018. (c) 2017 International Society for Magnetic
Resonance in Medicine.
PMID- 28686797
TI - Asiatic acid enhances survival of human AC16 cardiomyocytes under hypoxia by
upregulating miR-1290.
AB - Asiatic acid (AA) could attenuate ischemia/reperfusion induced myocardial
apoptosis through upregulating the Akt/GSK-3beta/HIF-1alpha pathway. HIF-3alpha
is a negative regulator of HIF-1alpha, whose mRNA is a potential target of miR
1290. AA could upregulate miR-1290 in non-small-cell lung cancer A549 cells. This
work aimed to investigate whether AA could inhibit hypoxia induced cardiomyocyte
apoptosis through regulating the miR-1290/HIF3A/HIF-1alpha axis. The AC16 human
myocardial cell line cultured under normoxic or hypoxic conditions was treated
with various doses of AA for 24 h. Afterwards cell viability, apoptosis and the
expression of miR-1290, HIF3A, and HIF1A were evaluated. Cells transfected with
miR-1290 mimic or inhibitor were used to determine the role of miR-1290 in the
anti-apoptosis effect of AA and the expression of HIF3A and HIF1A. Dual
luciferase assay was performed to confirm miR-1290 targeting of HIF3A. HIF3A
overexpression was achieved by transfection of HIF3A1 overexpressing lentivirus,
and its effect on miR-1290 and AA-regulated survival of cardiomyocytes was
evaluated. AA treatment protected cardiomyocytes from hypoxia-induced apoptosis
and upregulated miR-1290 and HIF1A, but downregulated HIF3A under hypoxia. The
protective effect of AA was abolished by miR-1290 knockdown, whereas enhanced by
miR-1290 overexpression. In addition, miR-1290 knockdown increased HIF1A
expression, but reduced HIF3A expression in cardiomyocytes. Dual luciferase assay
confirmed miR-1290 direct targeting the 3' UTR of HIF3A. HIF3A overexpression
counteracted the anti-apoptosis effect of AA or miR-1290. In conclusion, AA can
protect cardiomyocytes against hypoxia-induced apoptosis through regulating the
miR-1290/HIF3A/HIF-1alpha axis, and miR-1290 may be a potential target in the
prevention of myocardial ischemia-reperfusion injury. (c) 2017 IUBMB Life,
69(9):660-667, 2017.
PMID- 28686798
TI - multiplierz v2.0: A Python-based ecosystem for shared access and analysis of
native mass spectrometry data.
AB - The continued evolution of modern mass spectrometry instrumentation and
associated methods represents a critical component in efforts to decipher the
molecular mechanisms which underlie normal physiology and understand how
dysregulation of biological pathways contributes to human disease. The increasing
scale of these experiments combined with the technological diversity of mass
spectrometers presents several challenges for community-wide data access,
analysis, and distribution. Here we detail a redesigned version of multiplierz,
our Python software library which leverages our common application programming
interface (mzAPI) for analysis and distribution of proteomic data. New features
include support for a wider range of native mass spectrometry file types,
interfaces to additional database search engines, compatibility with new
reporting formats, and high-level tools to perform post-search proteomic
analyses. A GUI desktop environment, mzDesktop, provides access to multiplierz
functionality through a user friendly interface. multiplierz is available for
download from: https://github.com/BlaisProteomics/multiplierz; and mzDesktop is
available for download from: https://sourceforge.net/projects/multiplierz/.
PMID- 28686799
TI - Body Mass Index Category Moderates the Relationship Between Depressive Symptoms
and Diet Quality in Overweight and Obese Rural-Dwelling Adults.
AB - PURPOSE: This study was conducted to (1) compare diet quality among depressed and
nondepressed overweight and obese rural-dwelling adults and (2) determine whether
body mass index (BMI) category moderates the relationship between depressive
symptoms and overall diet quality. METHODS: Rural adults in Kentucky (n = 907)
completed the 9-item Patient Health Questionnaire (PHQ-9) that assessed
depressive symptoms and a food frequency questionnaire that generated 2005
Healthy Eating Index (HEI) scores. Participants were grouped into overweight (BMI
25-29.9 kg/m2 ) and obese (>=30 kg/m2 ), and nondepressed (PHQ-9 < 10) and
depressed (PHQ-9 >= 10) groups. Bootstrapped ANCOVAs were used to compare diet
quality among the 4 groups. Ordinary least-squares regression using PROCESS was
used to determine whether BMI category (overweight vs obese) moderated the
association between depressive symptoms and overall diet quality. RESULTS:
Overall diet quality was poorer in the obese depressed group than in the obese
nondepressed group. Intake of fruit and dark green/orange vegetables and legumes
was lower in the obese depressed group than in the overweight nondepressed group.
Depressive symptoms predicted poor overall diet quality (B = -0.287, P < .001)
and the relationship was moderated by BMI category (coefficient of BMI category*
depressive symptom interaction term = 0.355, P < .049). A significant inverse
relationship between depressive symptoms and overall diet quality was observed in
the overweight group but not in the obese group. CONCLUSION: Components of diet
quality vary according to BMI category and depressive symptom status. The
relationship between depressive symptoms and diet quality is influenced by BMI
category.
PMID- 28686800
TI - Accelerated three-dimensional multispectral MRI with robust principal component
analysis for separation of on- and off-resonance signals.
AB - PURPOSE: To enable highly accelerated distortion-free MRI near metal by
separating on- and off-resonance to exploit the redundancy of slice-phase
encoding for the dominant on-resonance component. METHODS: Multispectral MRI
techniques resolve off-resonance distortions by a combination of limited
excitation bins and additional encoding. Inspired by robust principal component
analysis, a novel compact representation of multispectral images as a sum of rank
one and sparse matrices corresponding to on- and off-resonance respectively is
described. This representation is used in a calibration-free and model-free
reconstruction for data with an undersampling pattern that varies between bins.
Retrospective undersampling was used to compare the proposed reconstruction and
bin-by-bin compressed sensing. Hip images were acquired in eight patients with
standard and prospectively undersampled three-dimensional multispectral imaging,
and image quality was evaluated by two radiologists on a 5-point scale. RESULTS:
Experiments with retrospective undersampling showed that the enhanced sparsity
afforded by the separation greatly reduces reconstruction errors and artifacts.
Images from prospectively undersampled multispectral imaging offered 2.6-3.4-fold
(18-24-fold overall) acceleration compared to standard multispectral imaging with
parallel imaging and partial-Fourier acceleration with equivalence in all
qualitative assessments within a tolerance of one point (P < 0.004). CONCLUSION:
Three-dimensional multispectral imaging can be highly accelerated by varying
undersampling between bins and separating on- and off-resonance. Magn Reson Med
79:1495-1505, 2018. (c) 2017 International Society for Magnetic Resonance in
Medicine.
PMID- 28686802
TI - Training Physical Therapists in Person-Centered Practice for People With
Osteoarthritis: A Qualitative Case Study.
AB - OBJECTIVE: To explore physical therapists' experiences with, and the impacts of,
a training program in person-centered practice to support exercise adherence in
people with knee osteoarthritis. METHODS: This was a qualitative case study using
semi-structured interviews, nested within a clinical trial. Eight Australian
physical therapists were interviewed before, and after, training in person
centered practice for people with knee osteoarthritis. Training involved a 2-day
workshop, skills practice, and audit of 8 consultations with 4 patients (per
therapist), and a final single-day workshop for audit feedback and consolidation.
Semi-structured interviews were audio-recorded and transcribed verbatim. Data
were thematically analyzed. RESULTS: Three pretraining themes arose regarding
usual communication style, definitions of person-centered care, and sharing
exercise adherence responsibility. Three themes related to the training
experience emerged: learning a new language, challenging conceptions of practice,
and putting it into practice. Post-training, 3 themes arose regarding new
knowledge deepening understanding of person-centered care, changing beliefs about
sharing responsibilities, and changed conceptions of role. CONCLUSION: Although
physical therapists found training overwhelming initially as they realized the
limitations of their current knowledge and clinical practice, they felt more
confident and able to provide person-centered care to people with knee
osteoarthritis by the end of training. Training in structured person-centered
methodology that provides opportunity for skills practice with patients using a
restructured consultation framework can change physical therapists' beliefs about
their roles when managing patients with osteoarthritis and positively impact
their clinical practice.
PMID- 28686801
TI - Exposure to complex environments results in more sparse representations of space
in the hippocampus.
AB - The neural circuitry mediating sensory and motor representations is adaptively
tuned by an animal's interaction with its environment. Similarly, higher order
representations such as spatial memories can be modified by exposure to a complex
environment (CE), but in this case the changes in brain circuitry that mediate
the effect are less well understood. Here, we show that prolonged CE exposure was
associated with increased selectivity of CA1 "place cells" to a particular
recording arena compared to a social control (SC) group. Furthermore, fewer CA1
and DG neurons in the CE group expressed high levels of Arc protein, a marker of
recent activation, following brief exposure to a completely novel environment.
The reduced Arc expression was not attributable to overall changes in cell
density or number. These data indicate that one effect of CE exposure is to
modify high-level spatial representations in the brain by increasing the sparsity
of population coding within networks of neurons. Greater sparsity could result in
a more efficient and compact coding system that might alter behavioural
performance on spatial tasks. The results from a behavioural experiment were
consistent with this hypothesis, as CE-treated animals habituated more rapidly to
a novel environment despite showing equivalent initial responding.
PMID- 28686803
TI - The calcium sensor synaptotagmin 1 is expressed and regulated in hippocampal
postsynaptic spines.
AB - Synaptotagmin 1 is a presynaptic calcium sensor, regulating SNARE-mediated
vesicle exocytosis of transmitter. Increasing evidence indicate roles of SNARE
proteins in postsynaptic glutamate receptor trafficking. However, a possible
postsynaptic expression of synaptotagmin 1 has not been demonstrated previously.
Here, we used postembedding immunogold electron microscopy to determine the
subsynaptic localization of synaptotagmin 1 in rat hippocampal CA1 Schaffer
collateral synapses. We report for the first time that synaptotagmin 1 is present
in rat hippocampal postsynaptic spines, both on cytoplasmic vesicles and at the
postsynaptic density. We further investigated whether postsynaptic synaptotagmin
1 is regulated during synaptic plasticity. In a rat model of chronic temporal
lobe epilepsy, we found that presynaptic and postsynaptic concentrations of the
protein are reduced compared to control animals. This downregulation may possibly
be an adaptive measure to decrease both presynaptic and postsynaptic calcium
sensitivity in excitotoxic conditions.
PMID- 28686804
TI - Smart Human-Serum-Albumin-As2 O3 Nanodrug with Self-Amplified Folate Receptor
Targeting Ability for Chronic Myeloid Leukemia Treatment.
AB - Arsenic trioxide (ATO, As2 O3 ) is currently used to treat acute promyelocytic
leukemia. However, expanding its use to include high-dose treatment of other
cancers is severely hampered by serious side effects on healthy organs. To
address these limitations, we loaded ATO onto folate (FA)-labeled human serum
albumin (HSA) pretreated with glutathione (GSH) based on the low pH- and GSH
sensitive arsenic-sulfur bond, and we termed the resulting smart nanodrug as FA
HSA-ATO. FA-HSA-ATO could specifically recognize folate receptor-beta-positive
(FRbeta+) chronic myeloid leukemia (CML) cells, resulting in more intracellular
accumulation of ATO. Furthermore, the nanodrug could upregulate FRbeta expression
in CML cancer cells and xenograft tumor model, facilitating even more recruitment
and uptake of FRbeta-targeting drugs. In vitro and in vivo experiments indicate
that the nanodrug significantly alleviates side effects and improves therapeutic
efficacy of ATO on CML and xenograft tumor model.
PMID- 28686805
TI - A generalized ratiometric chemical exchange saturation transfer (CEST) MRI
approach for mapping renal pH using iopamidol.
AB - PURPOSE: To extend the pH detection range of iopamidol-based ratiometric chemical
exchange saturation transfer (CEST) MRI at sub-high magnetic field and establish
quantitative renal pH MRI. METHODS: Chemical exchange saturation transfer imaging
was performed on iopamidol phantoms with pH of 5.5 to 8.0 and in vivo on rat
kidneys (n = 5) during iopamidol administration at a 4.7 T. Iopamidol CEST
effects were described using a multipool Lorentzian model. A generalized
ratiometric analysis was conducted by ratioing resolved iopamidol CEST effects at
4.3 and 5.5 ppm obtained under 1.0 and 2.0 uT, respectively. The pH detection
range was established for both the standard ratiometric analysis and the proposed
resolved approach. Renal pH was mapped in vivo with regional pH assessed by one
way analysis of variance. RESULTS: Good-fitting performance was observed in
multipool Lorentzian resolving of CEST effects (R2 s > 0.99). The proposed
approach extends the in vitro pH detection range to 5.5 to 7.5 at 4.7 T. In vivo
renal pH was measured to be 7.0 +/- 0.1, 6.8 +/- 0.1, and 6.5 +/- 0.2 for cortex,
medulla and calyx, respectively (P < 0.05). CONCLUSIONS: The proposed ratiometric
approach extended the iopamidol pH detection range, enabling the renal pH mapping
in vivo, which is promising for pH imaging studies at sub-high or low fields with
potential clinical applicability. Magn Reson Med 79:1553-1558, 2018. (c) 2017
International Society for Magnetic Resonance in Medicine.
PMID- 28686806
TI - Hippocampal damage causes retrograde but not anterograde memory loss for context
fear discrimination in rats.
AB - There is a substantial body of evidence that the hippocampus (HPC) plays and
essential role in context discrimination in rodents. Studies reporting
anterograde amnesia (AA) used repeated, alternating, distributed conditioning and
extinction sessions to measure context fear discrimination. In addition, there is
uncertainty about the extent of damage to the HPC. Here, we induced conditioned
fear prior to discrimination tests and rats sustained extensive, quantified pre-
or post-training HPC damage. Unlike previous work, we found that extensive HPC
damage spares context discrimination, we observed no AA. There must be a non-HPC
system that can acquire long-term memories that support context fear
discrimination. Post-training HPC damage caused retrograde amnesia (RA) for
context discrimination, even when rats are fear conditioned for multiple
sessions. We discuss the implications of these findings for understanding the
role of HPC in long-term memory.
PMID- 28686807
TI - Systematic review and meta-analysis of non-invasive prenatal DNA testing for
trisomy 21: implications for implementation in China.
AB - OBJECTIVES: To systematically review clinical validation studies of massive
parallel sequencing (MPS) technology in prenatal screening for trisomy 21 and to
explore the potential implementation strategies in China compared with those in
developing countries. METHODS: Searches of the Cochrane Library, Medline, EMBASE,
Web of Science, Biosis Previews, and three major Chinese databases were performed
to identify all the peer-reviewed articles published between 1 January 2011 and
15 October 2016. We also reviewed and discussed the potential challenges and
risks in the future promotion of MPS technology in China compared with those in
developing countries. RESULTS: The weighted pooled sensitivity and specificity of
MPS technology for the prenatal detection of trisomy 21 were 99.7% (95% CI 98.3
99.9%) and 100.0% (95% CI 99.9-100.0%), respectively, based on a meta-analysis of
44 included studies. An additional meta-analysis was conducted based on the 25
included studies that were performed in medical/genetic sequencing institutions
in mainland China, showing a weighted pooled sensitivity and specificity of MPS
technology as 99.5% (95% CI 98.7-99.8%) and 100% (95% CI 99.9-100%),
respectively. CONCLUSION: MPS technology offers effective screening performance
for trisomy 21 but should be cautiously promoted due to its clinical limitations
and challenges that stem from the ethics and business aspects. (c) 2017 John
Wiley & Sons, Ltd.
PMID- 28686808
TI - Integrating a Nurse-Midwife-Led Oral Health Intervention Into CenteringPregnancy
Prenatal Care: Results of a Pilot Study.
AB - INTRODUCTION: National and professional organizations recommend oral health
promotion in prenatal care to improve women's oral health. However, few prenatal
programs include education about oral health promotion. The objective of this
study was to determine if women receiving a brief, low-cost, and sustainable
educational intervention entitled CenteringPregnancy Oral Health Promotion had
clinically improved oral health compared to women receiving standard
CenteringPregnancy care. METHODS: Women attending CenteringPregnancy, a group
prenatal care model, at 4 health centers in the San Francisco Bay Area,
participated in this nonrandomized controlled pilot study in 2010 to 2011. The
intervention arm received the CenteringPregnancy Oral Health Promotion
intervention consisting of two 15-minute skills-based educational modules
addressing maternal and infant oral health, each module presented in a separate
CenteringPregnancy prenatal care session. The present analysis focused on the
maternal module that included facilitated discussions and skills-building
activities including proper tooth brushing. The control arm received standard
CenteringPregnancy prenatal care. Dental examinations and questionnaires were
administered prior to and approximately 9 weeks postintervention. Primary
outcomes included the Plaque Index, percent bleeding on probing, and percent of
gingival pocket depths 4 mm or greater. Secondary outcomes were self-reported
oral health knowledge, attitudes (importance and self-efficacy), and behaviors
(tooth brushing and flossing). Regression models tested whether pre to post
changes in outcomes differed between the intervention versus the control arms.
RESULTS: One hundred and one women participated in the study; 49 were in the
intervention arm, and 52 were in the control arm. The control and intervention
arms did not vary significantly at baseline. Significant pre to post differences
were noted between the arms with significant improvements in the intervention arm
for the Plaque Index, bleeding on probing, and pocket depths 4 mm or greater.
DISCUSSION: Providing brief oral health education and skills-building activities
within prenatal care may be effective in improving women's oral health during
pregnancy. These findings provide support for developing a full-scale randomized
clinical trial of the CenteringPregnancy Oral Health Promotion intervention.
PMID- 28686809
TI - Decision making in NICE single technological appraisals: How does NICE
incorporate patient perspectives?
AB - CONTEXT: The National Institute for Health and Care Excellence (NICE) has an
explicit mandate to include patient and public involvement in the appraisal of
medicines to be available for funding on the NHS. NICE involves an appraisal
committee who are required to take on board experiential evidence from patient
experts alongside population-based evidence on clinical and cost-effectiveness
when making a decision whether to fund a drug. OBJECTIVE: This paper considers
how NICE Single Technological Appraisal (STA) committees attempt to incorporate
the views of patients in making decisions about funding medicines on the NHS.
METHODS: A prospective design was employed to follow three pharmaceutical
products involving three different appraisal committees. Three data collection
methods were used: analysis of documentary evidence sent by NICE, non-participant
unstructured observations of the open and closed sessions of meetings and
qualitative interviews. SETTINGS AND PARTICIPANTS: Unstructured non-participant
observations were carried out at nine STA meetings, and 41 semi-structured
interviews were undertaken with committee members from NICE's STA committees,
patient experts, analysts from NICE's project team and drug manufacturers.
RESULTS: Our analysis showed how the committees displayed a preference for an
ideal-type of patient representative, disagreement among the committee when
weighing-up patient statements in the STA process and more pre-preparation
support for patient involvement. CONCLUSIONS: Although NICE has attempted to
adopt an approach flexible to patients and carers through formal decision-making
arrangements that incorporate patient views, nonetheless, the processes of the
STAs can in fact undermine the very evidence collected from patient
representatives.
PMID- 28686811
TI - Does glucosamine/chondroitin sulfate have a long-term effect on the progression
of structural changes in knee osteoarthritis? Comment on the article by Raynauld
et al.
PMID- 28686812
TI - Severity of disease, and not glucocorticoid use, determines outcomes in systemic
lupus: comment on the article by Sheane et al.
PMID- 28686810
TI - Self-calibrated correlation imaging with k-space variant correlation functions.
AB - PURPOSE: Correlation imaging is a previously developed high-speed MRI framework
that converts parallel imaging reconstruction into the estimate of correlation
functions. The presented work aims to demonstrate this framework can provide a
speed gain over parallel imaging by estimating k-space variant correlation
functions. METHODS: Because of Fourier encoding with gradients, outer k-space
data contain higher spatial-frequency image components arising primarily from
tissue boundaries. As a result of tissue-boundary sparsity in the human anatomy,
neighboring k-space data correlation varies from the central to the outer k
space. By estimating k-space variant correlation functions with an iterative self
calibration method, correlation imaging can benefit from neighboring k-space data
correlation associated with both coil sensitivity encoding and tissue-boundary
sparsity, thereby providing a speed gain over parallel imaging that relies only
on coil sensitivity encoding. This new approach is investigated in brain imaging
and free-breathing neonatal cardiac imaging. RESULTS: Correlation imaging
performs better than existing parallel imaging techniques in simulated brain
imaging acceleration experiments. The higher speed enables real-time data
acquisition for neonatal cardiac imaging in which physiological motion is fast
and non-periodic. CONCLUSION: With k-space variant correlation functions,
correlation imaging gives a higher speed than parallel imaging and offers the
potential to image physiological motion in real-time. Magn Reson Med 79:1483
1494, 2018. (c) 2017 International Society for Magnetic Resonance in Medicine.
PMID- 28686813
TI - Reply.
PMID- 28686814
TI - Early survival and delayed death of developmentally-born dentate gyrus neurons.
AB - The storage and persistence of memories depends on plasticity in the hippocampus.
Adult neurogenesis produces new neurons that mature through critical periods for
plasticity and cellular survival, which determine their contributions to learning
and memory. However, most granule neurons are generated prior to adulthood; the
maturational timecourse of these neurons is poorly understood compared to adult
born neurons but is essential to identify how the dentate gyrus (DG), as a whole,
contributes to behavior. To characterize neurons born in the early postnatal
period, we labeled DG neurons born on postnatal day 6 (P6) with BrdU and
quantified maturation and survival across early (1 hr to 8 weeks old) and late (2
6 months old) cell ages. We find that the dynamics of developmentally-born neuron
survival is essentially the opposite of neurons born in adulthood: P6-born
neurons did not go through a period of cell death during their immature stages
(from 1 to 8 weeks). In contrast, 17% of P6-born neurons died after reaching
maturity, between 2 and 6 months of age. Delayed death was evident from the loss
of BrdU+ cells as well as pyknotic BrdU+ caspase3+ neurons within the superficial
granule cell layer. Patterns of DCX, NeuN, and activity-dependent Fos expression
indicate that developmentally-born neurons mature over several weeks and a sharp
peak in zif268 expression at 2 weeks suggests that developmentally-born neurons
mature faster than adult-born neurons (which peak at 3 weeks). Collectively, our
findings are relevant for understanding how developmentally-born DG neurons
contribute to memory and disorders throughout the lifespan. High levels of early
survival and zif268 expression may promote learning, while also rendering neurons
sensitive to insults at defined stages. Late neuronal death in young adulthood
may result in the loss of hundreds of thousands of DG neurons, which could impact
memory persistence and contribute to hippocampal/DG atrophy in disorders such as
depression.
PMID- 28686815
TI - Re2 O7 -Mediated Dehydrative Cyclization Reactions: Total Synthesis of
Herboxidiene and Its 12-Desmethyl Analogue.
AB - Re2 O7 catalysis effects efficient and stereoselective dehydrative cyclization
reactions from monoallylic diols, with stereocontrol arising from thermodynamic
equilibration. This method was applied to a rapid synthesis of the spliceosome
inhibitor herboxidiene. The route was also utilized for the synthesis of an
analogue that highlights the importance of a single methyl group in biasing the
conformation in the acyclic region of the molecule.
PMID- 28686816
TI - First-Line, Non-Criterial Antiphospholipid Antibody Testing for the Diagnosis of
Antiphospholipid Syndrome in Clinical Practice: A Combination of Anti-beta2
Glycoprotein I Domain I and Anti-Phosphatidylserine/Prothrombin Complex
Antibodies Tests.
AB - OBJECTIVE: To assess the value of a combination of anti-beta2 -glycoprotein I
(anti-beta2 GPI) domain I antibody and anti-phosphatidylserine/prothrombin
complex (anti-PS/PT) antibody tests for the diagnosis of antiphospholipid
syndrome (APS). METHODS: This cross-sectional study involved a cohort of the
patients who visited our clinic from April 2005 to March 2013. Tests for anti
beta2 GPI domain I antibodies, IgG anti-PS/PT antibodies, and IgM anti-PS/PT
antibodies, together with tests for criteria-defined antiphospholipid antibodies
(aPL), were performed in all patients. The total antiphospholipid score (aPL-S)
was calculated for each patient according to titers of and positivity for aPL.
RESULTS: The study enrolled 157 patients (51 patients with APS and 106 with non
APS autoimmune diseases). All 21 patients positive for both anti-beta2 GPI domain
I antibodies and IgG and/or IgM (IgG/IgM) anti-PS/PT antibodies had APS with a
high total aPL-S (median 46, range 26-76), as did all of the 10 patients who were
positive for anti-beta2 GPI domain I antibodies but negative for IgG/IgM anti
PS/PT antibodies (median 22, range 4-39). Of the 14 patients who were positive
for IgG/IgM anti-PS/PT antibodies but negative for anti-beta2 GPI domain I
antibodies, 11 (79%) had APS; these individuals also had high total aPL-S values
(median 23, range 11-60). In contrast, only 9 of the 112 patients (8%) with none
of these antibodies had APS. CONCLUSION: The combination of the IgG anti-beta2
GPI domain I antibody and IgG/IgM anti-PS/PT antibody tests shows a high positive
predictive value for the diagnosis of APS and a strong correlation with the aPL
S. This combination as the first-line test for aPL may contribute to the simple
and definite identification of APS with a high risk of thrombosis in clinical
practice.
PMID- 28686817
TI - Affect and Incident Participation Restriction in Adults With Knee Osteoarthritis.
AB - OBJECTIVE: Participation restriction, common among people with knee
osteoarthritis (OA), may be influenced by affect. We examined the risk of
incident participation restriction over 84 months conferred by positive and
negative affect among people with knee OA. METHODS: Participants were from the
Multicenter Osteoarthritis Study and had or were at high risk of knee OA.
Participation restriction was measured using the Instrumental Role Limitation
subscale of the Late-Life Disability Index, and affect was measured using the
positive affect and depressed mood subscales of the Center for Epidemiologic
Studies Depression Scale. Robust Poisson regression was used to calculate the
risk of incident participation restriction over 84 months conferred by
combinations of low and high positive and negative affect, adjusting for
covariates. RESULTS: Of 1,810 baseline participants (mean age 62.1 years, 56%
female), 470 (26%) had incident participation restriction over 84 months.
Participants with low positive affect had 20% greater risk of incident
participation restriction than those with high positive affect; participants with
high negative affect had 50% greater risk of incident participation restriction
compared to those with low negative affect. Participants with both low positive
and high negative affect had 80% greater risk of incident participation
restriction compared to other combinations of positive and negative affect.
CONCLUSION: Low positive and high negative affect, both alone and in combination,
increase the risk of participation restriction among adults with knee OA. Efforts
aimed at preventing participation restriction in this population should consider
these mood states.
PMID- 28686818
TI - Antipsychotic Medication Treatment Patterns in Adult Depression.
AB - OBJECTIVE: To characterize the role of antipsychotic medications in the community
treatment of adult depression. METHODS: We identified adults (aged 18-64 years)
with new episodes of depression treatment (ICD-9-CM 296.2, 296.3, 300.4, or 311)
in US national Medicaid data (2001-2010). Patients with alternative ICD-9-CM
antipsychotic indications, such as schizophrenia or bipolar disorder, were
excluded. Each patient was followed for at least 1 year to characterize
antipsychotic and antidepressant treatment and emerging alternative antipsychotic
indications. For patients without alternative indications through day 45
following start of antipsychotic treatment, antipsychotics were considered to be
intended for treatment of depression. Among this group, we determined whether
antipsychotic initiation was preceded by minimally adequate treatment with
antidepressants, defined as active antidepressant treatment for >= 31 days prior
to and including the day of antipsychotic initiation. RESULTS: Within 1 year
following onset, 14.0% of patients started an antipsychotic medication. A total
of 41.3% of antipsychotic initiators developed an antipsychotic indication other
than depression through day 45 following antipsychotic initiation, most often
bipolar disorder or depression with psychotic features. The remaining 58.7% of
antipsychotic initiators presumably started antipsychotics for nonpsychotic
depression. Of these, 71.3% did not have minimally adequate antidepressant
treatment prior to starting the antipsychotic medication. CONCLUSION:
Antipsychotic medications are used in approximately 1 in 7 patients with a new
episode of depression. For 1 in 12 patients, the antipsychotic was considered to
be intended for nonpsychotic depression. Almost three-quarters of these patients
did not receive minimally adequate treatment with antidepressants prior to
antipsychotic initiation. This pattern suggests potentially inappropriate and
premature initiation of a drug class with substantial adverse effects and medical
risks.
PMID- 28686819
TI - Differential Risk of Increasing Psychotropic Polypharmacy Use in Children
Diagnosed With ADHD as Preschoolers.
AB - OBJECTIVE: To characterize treatment trajectories in children newly diagnosed
with attention-deficit/hyperactivity disorder (ADHD). METHODS: We utilized
billing records of children aged 3 to 18 years in 28 US states' Medicaid programs
between 1999 and 2006. Children entered the cohort at the first ADHD diagnosis
(ICD-9-CM: 314.00) preceded by >= 6 months with no psychotropic medication use
and no psychiatric diagnoses. We followed children for 5 years to assess use of
(1) psychotropic polypharmacy (the use of >= 3 psychotropic medication classes),
(2) antipsychotics, and (3) anticonvulsants. We used mixed-effects logistic
regression to model the probability of each utilization outcome as a function of
age at ADHD diagnosis and follow-up year, adjusted for sociodemographic factors.
RESULTS: Our cohort included 16,626 children of whom 79.2% received stimulants,
33.2% antidepressants, and 23.1% alpha-agonists, and 25.3% received psychotropic
polypharmacy treatment at least once in a subsequent year. Antipsychotics (7.1%
14.7%), anticonvulsants (4.0%-7.9%), and psychotropic polypharmacy (8.5%-13.4%)
use increased from year 1 to 5, but this increase was confined to children
between ages 3 and 9 at ADHD diagnosis. Children diagnosed at age 3 had the most
substantial increase in each outcome (OR = 1.80 [95% CI, 1.36-2.38]; 1.85 [1.38
2.47]; 2.14 [1.45-3.16]), respectively. Also, 39.1% of 9,680 children-years with
psychotropic polypharmacy therapy had no psychiatric diagnoses other than ADHD.
CONCLUSIONS: Psychotropic polypharmacy, antipsychotic, and anticonvulsant use
increased with each year of follow-up. This effect was strongly mediated by the
age of ADHD diagnosis with substantial increases in preschoolers but no
corresponding effect in older children. It was only partially explained by
physician diagnoses of concomitant mental disorders.
PMID- 28686820
TI - Cannabis Use and Cannabis Use Disorders Among Youth in the United States, 2002
2014.
AB - OBJECTIVE: To examine trends in past-year cannabis use (CU) and cannabis use
disorders (CUD) among youth in the United States, when related changes began, and
factors associated with these changes. METHODS: This study used data from 288,300
persons aged 12-17 years who participated in the 2002-2014 National Survey on
Drug Use and Health. Descriptive analyses and bivariable and multivariable
logistic regressions were applied (using the year 2002 as the reference group for
most analyses). RESULTS: The prevalence of past-year CU among youth decreased
from 15.8% in 2002 to 13.1% in 2014 (this downward trend occurred during 2002
2007 only [beta = -0.0540, P < .0001]). Among youth cannabis users, the
prevalence of past-year CUD decreased from 27.0% in 2002 to 20.4% in 2014, with a
downward trend starting in 2011 (beta = -0.0970, P = .0001). During 2002-2014,
the prevalence of past-year tobacco use and alcohol use decreased and prevalences
of past-year CU increased among tobacco users and among alcohol users. Our
multivariable results suggest that declines in past-year tobacco use (but not
alcohol use) among youth were associated with declines in past-year CU during
2010-2014. Past-year CU and CUD were higher among racial/ethnic minorities
(except for non-Hispanic Asians and Hawaiians/Pacific Islanders for CU) than non
Hispanic whites and were similar between male and female youth during 2002-2014.
CONCLUSIONS: In the United States, compared to 2002, even after adjusting for
covariates, CU decreased among youth during 2005-2014, and CUD declined among
youth cannabis users during 2013-2014. Associations between declines in tobacco
use and decreased CU suggest the importance of tobacco use control and prevention
among youth.
PMID- 28686821
TI - Gauging the Use of Second-Generation Antipsychotics: Medicaid Benefits Data
Suggest Much Room for Improvement.
PMID- 28686822
TI - Mindfulness-Based Stress Reduction for Older Adults With Stress Disorders and
Neurocognitive Difficulties: A Randomized Controlled Trial.
AB - OBJECTIVE: To determine whether neurocognitive performance and clinical outcomes
can be enhanced by a mindfulness intervention in older adults with stress
disorders and cognitive complaints. To explore decreased hypothalamic-pituitary
adrenal (HPA) axis activity as a possible mechanism. METHODS: 103 adults aged 65
years or older with an anxiety or depressive disorder (diagnosed according to DSM
IV criteria) and subjective neurocognitive difficulties were recruited in St.
Louis, Missouri, or San Diego, California, from September 2012 through August
2013 and randomly assigned in groups of 5-8 to mindfulness-based stress reduction
(MBSR) or a health education control condition matched for time, attention, and
credibility. The primary outcomes were memory (assessed by immediate and delayed
paragraph and list recall) and cognitive control (Delis-Kaplan Executive Function
System Verbal Fluency Test and Color Word Interference Test). Other outcomes
included clinical symptoms (worry, depression, anxiety, and global improvement).
HPA axis activity was assessed using peak salivary cortisol. Outcomes were
measured immediately post-intervention and (for clinical outcomes only) at 3- and
6-month follow up. RESULTS: On the basis of intent-to-treat principles using data
from all 103 participants, the mindfulness group experienced greater improvement
on a memory composite score (P = .046). Groups did not differ on change in
cognitive control. Participants receiving MBSR also improved more on measures of
worry (P = .042) and depression (P = .049) at posttreatment and on worry (P =
.02), depression (P = .002), and anxiety (P = .002) at follow-up and were more
likely to be rated as much or very much improved as rated by the Clinical Global
Impressions-Improvement scale (47% vs 27%, chi2 = 4.5, P = .03). Cortisol level
decreased to a greater extent in the mindfulness group, but only among those
participants with high baseline cortisol. CONCLUSIONS: In this population of
older adults with stress disorders and neurocognitive difficulties, a mindfulness
intervention improves clinical outcomes such as excessive worry and depression
and may include some forms of immediate memory performance. TRIAL REGISTRATION:
ClinicalTrials.gov identifier: NCT01693874.
PMID- 28686823
TI - Enhancing Extinction Learning in Posttraumatic Stress Disorder With Brief Daily
Imaginal Exposure and Methylene Blue: A Randomized Controlled Trial.
AB - OBJECTIVE: The memory-enhancing drug methylene blue (MB) administered after
extinction training improves fear extinction retention in rats and humans with
claustrophobia. Robust findings from animal research, in combination with
established safety and data showing MB-enhanced extinction in humans, provide a
foundation to extend this work to extinction-based therapies for posttraumatic
stress disorder (PTSD) such as prolonged exposure (PE). METHODS: Patients with
chronic PTSD (DSM-IV-TR; N = 42) were randomly assigned to imaginal exposure plus
MB (IE + MB), imaginal exposure plus placebo (IE + PBO), or waitlist (WL/standard
PE) from September 2011 to April 2013. Following 5 daily, 50-minute imaginal
exposure sessions, 260 mg of MB or PBO was administered. Waitlist controls
received PE following 1-month follow-up. Patients were assessed using the
independent evaluator-rated PTSD Symptom Scale-Interview version (primary
outcome), patient-rated PTSD, trauma-related psychopathology, and functioning
through 3-month follow-up. RESULTS: Both IE + MB and IE + PBO showed strong
clinical gains that did not differ from standard PE at 3-month follow-up. MB
augmented exposure specifically enhanced independent evaluator-rated treatment
response (number needed to treat = 7.5) and quality of life compared to placebo
(effect size d = 0.58). Rate of change for IE + MB showed a delayed initial
response followed by accelerated recovery, which differed from the linear pattern
seen in IE + PBO. MB effects were facilitated by better working memory but not by
changes in beliefs. CONCLUSIONS: The findings provide preliminary efficacy for a
brief IE treatment for PTSD and point to the potential utility of MB for
enhancing outcome. Brief interventions and better tailoring of MB augmentation
strategies, adjusting for observed patterns, may have the potential to reduce
dropout, accelerate change, and improve outcomes. TRIAL REGISTRATION:
ClinicalTrials.gov identifier: NCT01188694.
PMID- 28686824
TI - Interplay between antiretroviral therapy and oxidative stress in HIV seropositive
patients.
AB - BACKGROUND: HIV infection results in a decline of CD4+ T-cells count and
ultimately results in qualitative impairments of CD4+ T-cell function.
Antiretroviral therapy results in an increase in the number of CD4+ cells and the
functional reconstitution of the immune system. However, patients on therapy
commonly experience adverse effects; management of HIV infection thus becomes a
balancing act between the benefits of HIV suppression and the risks of drug
toxicity with Highly Active Antiretroviral Therapy (HAART). Purpose and Findings:
This review intended to look into the relationship between adverse effects with
HAART in relation to its induction of oxidative stress in the host. From
literature,. HAART has been shown to induce oxidative stress by several
biochemical mechanisms. However, the induction of oxidative stress by HAART is
minimal compared to HIV induction of oxidative stress-in the host. The use of
HAART in the management of HIV-AIDS thus remains inevitable and the combination
with exogenous antioxidants is advocated. Exogenous antioxidants mop up infection
induced reactive oxygen species (ROS), and may also be beneficial in ameliorating
some of the adverse effects induced by HAART. CONCLUSION: Further review on
individual adverse effects of ART is recommended and our ongoing research on the
teratogenic potentials of HAART will also be very relevant on this subject.
PMID- 28686825
TI - Overview of radiation dose to patients from medical X-ray examinations in
Nigeria.
AB - OBJECTIVES: Medical Imaging accounts for the largest radiation exposure of
population from artificial sources of radiation. The radiation dose rcceivedby
patients from iedicail x-ray examinations in Nigeria has shown large variations
within and among diagnostic centers for similar examinations. This could be
traced to lack of imaging protocols and on avalability of local/national
diagnostic reference, levels. Hence, the need to assess the trend of radiation
doseto patients from radiological practice in Nigeria. Methocls:Entrance surface
doses(ESDs) reported by, Nigerian authors for common x-ray examinations from 2000
- 2014 were extracted from articles published in peer reviewed journals, analyzed
and compared with ifiternationally recommended Diagnostic Reference Levels
(DkLs). RESULTS: Among x-ray examinations, skull accounted for 32% followed by
chest (22%), lumbar spine (13%), abdomen (12%), pelvis (8%), extremitics(8%),
thorax and cervical spine(5%). The range of mean ESDs reported for various
projections of x-ray examination are chest (2.28 - 3.70 mGy); Abdomen (4.42 -
7.22 mGy); Skull (3.81 - 5.19 mGy); Pelvis (5.93 mGy); Lumbar spine (5.73 - 10.98
mGy); Thorax (0.96 - 1.85 mGy); Cervical spine (1.45 - 1.49mGy) and Extremitics
(0.31 -0.49 mGy). In this study, it was found that the mean ESDs received by
patients from chest, skull and pelvis ex'aminations were higher than the
published DRLs for similar x-ray examinations. CONCLUSION: The results of this
study showed that to harmonize radiation protection of patients and improve
radiological practice in Nigeria there is need for development of comprehensive
national diagnostic reference levels.
PMID- 28686826
TI - Oxygen for children and newborns in non-tertiary hospitals in South-west Nigeria:
A needs assessment.
AB - BACKGROUND: Oxygen is important for the treatment of hypoxaemia associated with
pneumonia, malaria, and other medical, obstetric, and surgical conditions. Access
to oxygen therapy is limited in many of the high mortality settings where it
would be of most benefit. METHODS: A needs assessment of 12 non-tertiary
hospitals in south-west Nigeria, assessing structural, technical and clinical
barriers to the provision of safe and effective oxygen therapy. RESULTS: Oxygen
supply was reported to be a major challenge by hospital directors. All hospitals
had some access to oxygen cylinders, which were expensive and frequently ran out.
Nine (75%) hospitals used oxygen concentrators, which were limited by inadequate
power supply and lack of maintenance capacity. Appropriate oxygen delivery and
monitoring devices (nasal prongs, catheters, pulse oximeters) were poorly
available, and no hospitals had clinical guidelines pertaining to the use of
oxygen for children. Oxygen was expensive to patients (median US$20/day) and to
hospitals. Estimated oxygen demand is reported using both a constant mean-based
estimate and adjustment for seasonal and other variability. CONCLUSIONS: Making
oxygen available to sick children and neonates in Nigerian hospitals will
require: improving detection of hypoxaemia through routine use of pulse oximetry;
improving access to oxygen through equipment, training, and maintenance
structures; and commitment to building hospital and state structures that can
sustain and expand oxygen initiatives.
PMID- 28686827
TI - Is there any relationship between hearing threshold levels and CD4 cell count of
human immunodeficiency virus infected adults?
AB - : Background The role of viral load level and/or CD4 (Cluster of differentiation
4) cell count in the aetiopathogenesis of hearing loss in HIV infection is
unclear. Therefore, we investigated the relationship between CD4 cell counts,
viral load and hearing threshold of HIV (Human immunodeficiency virus) infected
adults. METHODS: This cohort audiometric study involved consecutive HIV-infected
and HIV-uninfected adults as controls. Clinical data relating to hearing loss,
HIV status, and highly -active antiretroviral therapy (HAART) were obtained.
Audiornetric evaluation was performed. The most recent CD4 cell counts and RNA
viral load-of HIV-infected participants were obtained from clinic records.
RESULTS: There were 299(66.7%) HIV-infected adults and 149(33.3%) controls with
mean age of 39.64+/- 12.45 years and 39.60+/-12.45 years respectively (p=0.98).
In both groups, there were more participants with left hearing loss. Mild to
profound hearing loss was found in 65.9% HIV- infected participants and 53.7%
controls. Majority (86.3%) of the HIV-infected participants were on HAART. The
mean CD4 cell count was 654.58+/-289.15 in 41 HIV-infected participants not on
HAART and 523.95+/-300.17 in 258 participants on HAART (p=0.01). Majority,- 197
(62%) HIV- infected participants with hearing loss had CD4 cell count <=200
cells/mm3. Higher viral load significantly correlated with low CD4 cell counts
(p<0.0 1; r=0. 18) and low CD4 cell count significantly correlated with high
hearing threshold (p0.5 also showed highest sensitivity in both genders in
identifying CMS and clusters of >2 CMS risk factors, but with lowest specificity
and positive likelihood ratio (LR+). ATPIII WC cut-off revealed lowest
sensitivity and highest specificity in screening CMS and >2 CMS risk factors in
males (p<0.000l). IDF WC-threshold had the more stable sensitivity and
specificity in males (p<0.0001) but not in females. CONCLUSION: WHtR>0.5 is more
sensitive than WC and BMI recommended values in screening for CMS, but with the
least positive likelihood ratio. However, more studies in other nations of sub
Saharan Africa are needed to assure evaluation of different cut points that will
yield optimal specificity and sensitivity. This will help curb the problem of
over-diagnosis of CMS risk factors and increase better health outcome of the
population.
PMID- 28686834
TI - Noncovalent Interactions by Fixed-Node Diffusion Monte Carlo: Convergence of
Nodes and Energy Differences vs Gaussian Basis-Set Size.
AB - Convergence of fixed-node (FN) shape and FN diffusion Monte Carlo (FNDMC)
interaction energies is studied vs the Gaussian basis set saturation level in HF
and CH4 dimers and one-determinant Slater-Jastrow trial wave functions (PsiT).
The tested 25 distinct basis sets obtained by stepwise trimming of aug-VDZ and
aug-VTZ bases suggest minimum basis set requirements to achieve reasonable
results. A single selected trimmed basis set, about 2 times smaller in size than
aug-VTZ, is extensively tested on a set of 12 noncovalent complexes including
formic acid dimer, benzene-methane, or coronene-H2. The results indicate that
equivalent noncovalent FNDMC energy differences are available at costs lower than
assumed before. Additional insights from electron density differences and
comparison of dimer vs monomer PsiT nodes explain this observation.
PMID- 28686833
TI - Anti-oxidative and reno-restorative effects of physalis angulata (whole plant
extract) in alloxan-induced diabetic male Wistar rats.
AB - : Backgroiound: Hyperglycemia has been reported to increase protein glycation and
generation of free radicals which predispose to diabetic renal dysfunction.
Physalis ahgulata has been shown to have hypoglycacmic and anti-lipidemic
properties but there is dearth of information regarding its effect on kidney
functions in diabetes. This study investigated the anti-oxidative and reno
restorative effects of methanol extract of whole plant of Physalis angulata
(MEPA) in alloxan-induced diabetic rats. METHODOLOGY: Twenty male Wistar rats
(150-180g) were randomly divided into four groups: Group 1 (control) received 0.2
ml distilled water, groups 2-4 were made diabetic by single intra-peritoneal dose
of alloxan monohydrate (100mg/kg) and treated with 0.2 ml distilled water, 500
mg/kg MEPA and 150 mg/kg metformin respectively. All treatments were given orally
for 14 days. Blood samples were collected from each animal through retro-orbital
puncture. The serum obtained were analysed for fructosamine, glycated hemoglobin
(HbAlc), creatinine and blood urea nitrogen (BUN). Kidney samples were harvested
into cold phosphate buffer, homogenized and centrifuged at- 7500rpm for 15
minutes. The supernatant obtained was analyzed for malondialdehyde and superoxide
dismutase (SOD) activities. Values were compared using ANOVA at P<0.05. RESULTS:
The MEPA-treated groups showed significant decrease (P<0.05) in blood glucose,
kidney weights, fructosamine,. HbAlc, malondialdehyde, creatinine and BUN, while
the body weights and SOD significantly increased (P<0.05) compared to diabetic
untreated group. CONCLUSION: Treatment with methanol extract of Physalis angulata
(whole plant) reduced hyperglycemia, malondialdehyde and glycation end- products,
which could have contributed to the development of diabetic nephropathy if
diabetes is left untreated.
PMID- 28686835
TI - Various Antioxidant Effects Were Attributed to Different Components in the Dried
Blossoms of Citrus aurantium L. var. amara Engl.
AB - Citrus aurantium L. var. amara Engl. (CAVA) was traditionally used as an edible
and medicinal material in China. Total flavonoids (CAVAF), alkaloids (CAVAA),
polysaccharides (CAVAP), coumarins (CAVAC), and neroli (CAVAO) were extracted
from CAVA. Hesperidin, naringin, and neohesperidin composed 83.94% of CAVAF, and
synephrine represented 50.56% of CAVAA. On the basis of 1,1-diphenyl-2
picrylhydrazyl radical (DPPH*), 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic
acid) diammonium salt radical cation (ABTS* +), hydroxyl radical (*OH), ferric
reducing antioxidant power (FRAP), and reducing power assays, the antioxidant
activities of five components were comprehensively and comparatively
investigated. CAVAF had a stronger DPPH* scavenging effect and FRAP and reducing
power. CAVAP and CAVAA exhibited comparable *OH scavenging effects to vitamin C.
CAVAA showed the highest ABTS* + scavenging activity. In conclusion, different
constituents varied significantly toward different sources of free radicals and
other oxidants. It is obvious that CAVA has various antioxidant effects, which
are attributed to different components.
PMID- 28686837
TI - Tethering Luminescent Thermometry and Plasmonics: Light Manipulation to Assess
Real-Time Thermal Flow in Nanoarchitectures.
AB - The past decade has seen significant progresses in the ability to fabricate new
mesoporous thin films with highly controlled pore systems and emerging
applications in sensing, electrical and thermal isolation, microfluidics, solar
cells engineering, energy storage, and catalysis. Heat management at the micro-
and nanoscale is a key issue in most of these applications, requiring a complete
thermal characterization of the films that is commonly performed using electrical
methods. Here, plasmonic-induced heating (through Au NPs) is combined with
Tb3+/Eu3+ luminescence thermometry to measure the thermal conductivity of silica
and titania mesoporous nanolayers. This innovative method yields values in accord
with those measured by the evasive and destructive conventional 3omega-electrical
method, simultaneously overcoming their main limitations, for example, a
mandatory deposition of additional isolating and metal layers over the films and
the previous knowledge of the thermal contact resistance between the heating and
the mesoporous layers.
PMID- 28686836
TI - Hydrophobic Patch of Ubiquitin is Important for its Optimal Activation by
Ubiquitin Activating Enzyme E1.
AB - Protein ubiquitination plays a role in essentially every process in eukaryotic
cells. The attachment of ubiquitin (Ub) or Ub-like (UBL) proteins to target
proteins is achieved by parallel but distinct cascades of enzymatic reactions
involving three enzymes: E1, E2, and E3. The E1 enzyme functions at the apex of
this pathway and plays a critical role in activating the C-terminus of ubiquitin
or UBL, which is an essential step that triggers subsequent downstream transfer
to their cognate E2s resulting in the fidelity of the Ub/UBL conjugation
machinery. Despite the central role of the E1 enzyme in protein modification, a
quantitative method to measure Ub/UBL activation by E1 is lacking. Here, we
present a mass spectrometry-based assay to accurately measure the activation of
Ub/UBL by E1 independent of the E2/E3 enzymes. Our method does not require
radiolabeling of any components and therefore can be used in any biochemical
laboratory having access to a mass spectrometer. This method allowed us to
dissect the concerted process of E1-E2-catalyzed Ub conjugation in order to
separately characterize the process of Ub activation and how it is affected by
select mutations and other factors. We found that the hydrophobic patch of Ub is
important for the optimal activation of Ub by E1. We further show that the
blockers of the Ub-proteasome system such as ubistatin and fullerenol inhibit Ub
activation by E1. Interestingly, our data indicate that the phosphorylation of Ub
at the S65 position augments its activation by the E1 enzyme.
PMID- 28686838
TI - Occurrence of the (2R,3S)-Isomer of 2-Amino-3,4-dihydroxybutanoic Acid in the
Mushroom Hypsizygus marmoreus.
AB - Here, we report the occurrence of the (2R,3S)-isomer of 2-amino-3,4
dihydroxybutanoic acid (d-ADHB) in the fruiting body of an edible mushroom,
Hypsizygus marmoreus. This is an unusual example of the accumulation of a d-amino
acid whose enantiomer is not a proteinogenic amino acid. We show that d-ADHB
occurs specifically in the mushroom H. marmoreus. Other edible mushrooms
examined, including Pholiota microspora, Pleurotus eryngii, Mycena chlorophos,
Sparassis crispa, Grifola frondosa, Pleurotus ostreatus, and Flammulina
velutipes, do not contain detectable levels of d-ADHB. The concentration of d
ADHB in the fruiting body of H. marmoreus is relatively high (approximately 1.3
mg/g of fruiting body) and is comparable to the concentration of some of the most
abundant free proteinogenic amino acids. Quantitative analysis of d-ADHB during
fruiting body development demonstrated that the amino acid is synthesized during
the fruiting body formation period. The absence of the putative precursors of d
ADHB, the (2S,3S)-isomer of ADHB and 2-oxo-tetronate, and the enzyme activities
of d-ADHB racemase (2-epimerase) and transaminase suggested that d-ADHB is
synthesized by a unique mechanism in this organism. Our data also suggested that
the lack of or low expression of a d-ADHB degradation enzyme is a key determinant
of d-ADHB accumulation in H. marmoreus.
PMID- 28686839
TI - On-the-Fly CASPT2 Surface-Hopping Dynamics.
AB - We report the development of programs for on-the-fly surface-hopping dynamics
simulations in the gas and condensed phases on the potential energy surfaces
computed by multistate multireference perturbation theory (XMS-CASPT2) with full
internal contraction. On-the-fly nonadiabatic dynamics simulations are made
possible by improving the algorithm for XMS-CASPT2 nuclear energy gradient and
derivative coupling evaluation. The program is interfaced to a surface-hopping
dynamics program, Newton-X, and a classical molecular dynamics package, tinker,
to realize such simulations. On-the-fly XMS-CASPT2 surface-hopping dynamics
simulations of 9H-adenine and an anionic GFP model chromophore (para
hydroxybenzilideneimidazolin-5-one) in water are presented to demonstrate the
applicability of our program to sizable systems. Our program is implemented in
the bagel package, which is publicly available under the GNU General Public
License.
PMID- 28686840
TI - Carboxylate Counteranions in Electronic Cigarette Liquids: Influence on Nicotine
Emissions.
AB - The wide pH range reported for electronic cigarette (ECIG) liquids indicates that
nicotine may be present in one or more chemical forms. The nicotine form affects
the bioavailability and delivery of nicotine from inhaled products. Protonated
nicotine is normally associated with counteranions in tobacco products. The
chemical and physical properties of counteranions may differently influence the
nicotine form and emissions in ECIG aerosols. In this study, we examined how
these anions influence nicotine emissions and their evaporation behavior and
potential decomposition during ECIG operation. ECIG liquid solutions with equal
nicotine concentration and pH but different counteranions (formate, acetate, and
citrate) were prepared from analytical standards to assess the effect of the
counteranion on nicotine partitioning. High performance liquid and gas
chromatography methods were developed to determine the counteranions and the two
protonated (NicH+) and free base (Nic) forms of nicotine in commercially
available and standard solutions of ECIG liquids and aerosols. In commercial
samples, acetate and citrate anions were detected. In standard solutions, both
formate and acetate ions were found to evaporate intact, but citrate ion
decomposed into formic acid and other products. This study also shows that the
identity of the counteranion has no effect on total nicotine emission from ECIG
in agreement with previous reports on tobacco cigarettes. However, the
partitioning of aerosolized nicotine into NicH+ and Nic is anion-dependent even
when the parent liquid pH is held constant. These results indicate that the
anions found in a given ECIG product may influence the nicotine delivery profile
to the user by enriching aerosols with free-base nicotine as in the case of
polycarboxylic acids such as citric acid.
PMID- 28686841
TI - Absorption Spectra for Disordered Aggregates of Chromophores Using the Exciton
Model.
AB - Optimizing the optical properties of large chromophore aggregates and molecular
solids for applications in photovoltaics and nonlinear optics is an outstanding
challenge. It requires efficient and reliable computational models that must be
validated against accurate theoretical methods. We show that linear absorption
spectra calculated using the molecular exciton model agree well with spectra
calculated using time-dependent density functional theory and configuration
interaction singles for aggregates of strongly polar chromophores. Similar
agreement is obtained for a hybrid functional (B3LYP), a long-range corrected
hybrid functional (omegaB97X), and configuration interaction singles. Accounting
for the electrostatic environment of individual chromophores in the
parametrization of the exciton model with the inclusion of atomic point charges
significantly improves the agreement of the resulting spectra with those
calculated using all-electron methods; different charge definitions (Mulliken and
ChelpG) yield similar results. We find that there is a size-dependent error in
the exciton model compared with all-electron methods, but for aggregates with
more than six chromophores, the errors change slowly with the number of
chromophores in the aggregate. Our results validate the use of the molecular
exciton model for predicting the absorption spectra of bulk molecular solids; its
formalism also allows straightforward extension to calculations of nonlinear
optical response.
PMID- 28686842
TI - QM/MM Calculation of the Enzyme Catalytic Cycle Mechanism for Copper- and Zinc
Containing Superoxide Dismutase.
AB - The entire enzyme catalytic mechanism including the electron and the proton
transfers of the copper- and zinc-containing extracellular superoxide dismutase
(SOD3) was investigated by using QM/MM method. In the first step, the electron
transfer from O2.- to SOD3 occurred without the bond formation between the donor
and the acceptor and formed the triplet oxygen molecule and reduced SOD3. In the
reduced SOD3, the distorted tetrahedral structure of Cu(I) atom was maintained.
The reduction of Cu(II) atom induced the protonation of His113, which bridges
between the Cu(II) and Zn(II) atoms in the resting state. Since the protonation
of His113 broke the bond between Cu(I) and His113, three-coordinated Cu(I) was
formed. Further, we suggest the binding of O2.- formed hydrogen peroxide and the
resting state after both the Cu reduction and the protonation of His113. The
protonation of His113 caused the conformational change of Arg186 located at the
entrance of the reactive site. The electrostatic potential surface around the
reactive site showed that Arg186 plays an important role as electrostatic
guidance for the negatively charged substrates only after the protonation of
His113. The rotation of Arg186 switched the proton supply routes via Glu108 or
Glu179 for transferring two protons from the bulk solvent.
PMID- 28686843
TI - Cadmium Concentration in Grains of Durum Wheat (Triticum turgidum L. subsp.
durum).
AB - Heavy metal excess in soil represents a critical problem for crop productivity.
Among these pollutants, cadmium (Cd) is one of the most dangerous in terms of
food-chain contamination. Two durum wheat near-isogenic lines (NILs) and 12
commercial varieties (cultivars Arcangelo, Aureo, Aziziah, Cappelli, Cirillo,
Creso, Iride, Maestrale, Parsifal, Russello, Strongfield, and Svevo) of durum
wheat were exposed to a nontoxic level of Cd to evaluate its concentration in
grains, roots, and shoots, as well as effects on biomass production. Cultivar
Iride showed the most interesting behavior because it stored large amounts of Cd
in the roots, preventing its translocation to grains. On the contrary, Cirillo
and Svevo genotypes were characterized by a high Cd concentration in the grains.
Furthermore, a molecular characterization employing the ScOPC20 marker associated
with the Cd uptake locus has shown the absence of the expected fragment in the
Iride variety and in other varieties characterized by low Cd concentration, as
well as the presence of it in high Cd-accumulating cultivars.
PMID- 28686844
TI - Guidelines for the Provision and Assessment of Nutrition Support Therapy in the
Pediatric Critically Ill Patient: Society of Critical Care Medicine and American
Society for Parenteral and Enteral Nutrition.
AB - This document represents the first collaboration between 2 organizations-the
American Society for Parenteral and Enteral Nutrition and the Society of Critical
Care Medicine-to describe best practices in nutrition therapy in critically ill
children. The target of these guidelines is intended to be the pediatric
critically ill patient (>1 month and <18 years) expected to require a length of
stay >2-3 days in a PICU admitting medical, surgical, and cardiac patients. In
total, 2032 citations were scanned for relevance. The PubMed/MEDLINE search
resulted in 960 citations for clinical trials and 925 citations for cohort
studies. The EMBASE search for clinical trials culled 1661 citations. In total,
the search for clinical trials yielded 1107 citations, whereas the cohort search
yielded 925. After careful review, 16 randomized controlled trials and 37 cohort
studies appeared to answer 1 of the 8 preidentified question groups for this
guideline. We used the GRADE criteria (Grading of Recommendations, Assessment,
Development, and Evaluation) to adjust the evidence grade based on assessment of
the quality of study design and execution. These guidelines are not intended for
neonates or adult patients. The guidelines reiterate the importance of nutrition
assessment-particularly, the detection of malnourished patients who are most
vulnerable and therefore may benefit from timely intervention. There is a need
for renewed focus on accurate estimation of energy needs and attention to
optimizing protein intake. Indirect calorimetry, where feasible, and cautious use
of estimating equations and increased surveillance for unintended caloric
underfeeding and overfeeding are recommended. Optimal protein intake and its
correlation with clinical outcomes are areas of great interest. The optimal route
and timing of nutrient delivery are areas of intense debate and investigations.
Enteral nutrition remains the preferred route for nutrient delivery. Several
strategies to optimize enteral nutrition during critical illness have emerged.
The role of supplemental parenteral nutrition has been highlighted, and a delayed
approach appears to be beneficial. Immunonutrition cannot be currently
recommended. Overall, the pediatric critical care population is heterogeneous,
and a nuanced approach to individualizing nutrition support with the aim of
improving clinical outcomes is necessary.
PMID- 28686845
TI - Metabolomics and fetal alcohol spectrum disorder.
AB - Fetal alcohol spectrum disorder (FASD) is a major public health issue that
encompass an array of physical, neurological, and behavioral effects due to
alcohol consumption during pregnancy. The classical biomarkers of FASD that are
currently used lack sensitivity and specificity, and as such there is an
opportunity through the use of novel metabolomics analysis to identify new
biomarkers to identify those at risk for FASD, which could more effectively aid
in early intervention. The focus of this minireview is to identify current work
that is being done in the field of metabolomics in FASD in utero, and to
highlight promising metabolites that could act as biomarkers in the future. We
will conclude with suggestions for further research, as there is a large gap of
knowledge in this particular area of metabolomics.
PMID- 28686846
TI - Effect of First Tarsometatarsal Joint Derotational Arthrodesis on First Ray
Dynamic Stability Compared to Distal Chevron Osteotomy.
AB - BACKGROUND: Hallux valgus alters gait, compromising first ray stability and
function of the windlass mechanism at the late stance. Hallux valgus correction
should restore the stability of the first metatarsal. Comparative studies
reporting the impact of different hallux valgus correction methods on gait are
rare. We report the results of a case-control study between distal chevron
osteotomy and first tarsometatarsal joint derotational arthrodesis (FTJDA).
METHODS: Two previously studied hallux valgus cohorts were matched: distal
chevron osteotomy and FTJDA. Seventy-seven feet that underwent distal chevron
osteotomy (chevron group) and 76 feet that underwent FTJDA (FTJDA group) were
available for follow-up, with a mean of 7.9 years (range, 5.8-9.4 years) and 5.1
years (range, 3.0-8.3 years), respectively. Matching criteria were the hallux
valgus angle (HVA) and a follow-up time difference of a maximum 24 months. Two
matches were made: according to the preoperative HVA and the HVA at late follow
up. Matching provided 30 and 31 pairs, respectively. Relative impulses (%) of the
first toe (T1) and metatarsal heads 1 to 5 (MTH1-5), weightbearing radiographs,
and American Orthopaedic Foot & Ankle Society (AOFAS) (hallux metatarsophalangeal
interphalangeal [MTP-IP]) scores were studied. RESULTS: The relative impulse of
MTH1 was higher in the FTJDA group, whereas a central dynamic loading pattern was
seen in the chevron group. This result remained when relative impulses were
analyzed according to the postoperative HVA. The mean difference in the HVA at
follow-up was 6.2 degrees (95% confidence interval, 3.0-9.5; P = .001) in favor
of the FTJDA group. CONCLUSION: The dynamic loading capacity of MTH1 was higher
in the FTJDA group in comparison to the chevron group. The follow-up HVA remained
better in the FTJDA group. LEVEL OF EVIDENCE: Level III, case-control study.
PMID- 28686847
TI - Development and Implementation of an HTS-Compatible Assay for the Discovery of
Selective Small-Molecule Ligands for Pre-microRNAs.
AB - microRNAs (miRNAs) are small gene regulatory RNAs, and their expression has been
found to be dysregulated in a number of human diseases. To facilitate the
discovery of small molecules capable of selectively modulating the activity of a
specific miRNA, we have utilized new high-throughput screening technology
targeting Dicer-mediated pre-miRNA maturation. Pilot screening of ~50,000 small
molecules and ~33,000 natural product extract libraries against pre-miR-21
processing indicated the potential of our assay for this goal, yielding a
campaign Z' factor of 0.52 and an average plate signal-to-background (S/B) ratio
of 13. Using two-dimensional screening against a second pre-miRNA, pre-let-7d, we
evaluated the selectivity of confirmed hits. The results presented demonstrate
how high-throughput screening can be used to identify selective small molecules
for a target RNA.
PMID- 28686848
TI - Transcriptional regulation of endothelial-to-mesenchymal transition in cardiac
fibrosis: role of myocardin-related transcription factor A and activating
transcription factor 3.
AB - The etiology of cardiac fibrogenesis is quite diverse, but a common feature is
the presence of activated fibroblasts. Experimental evidence suggests that a
subset of cardiac fibroblasts is derived via transition of vascular endothelial
cells into fibroblasts by endothelial-to-mesenchymal transition (EndMT). During
EndMT, endothelial cells lose their endothelial characteristics and acquire a
mesenchymal phenotype. Molecular mechanisms and the transcriptional mediators
controlling EndMT in heart during development or disease remain relatively
undefined. Myocardin-related transcription factor A facilitates the transcription
of cytoskeletal genes by serum response factor during fibrosis; therefore, its
specific role in cardiac EndMT might be of importance. Activation of activating
transcription factor 3 (ATF-3) during cardiac EndMT is speculative, since ATF-3
responds to a transforming growth factor beta (TGF-beta) stimulus and controls
the expression of the primary epithelial-to-mesenchymal transition markers Snail,
Slug, and Twist. Although the role of TGF-beta in EndMT-mediated cardiac fibrosis
has been established, targeting of the TGF-beta ligand has not proven to be a
viable anti-fibrotic strategy owing to the broad functional importance of this
ligand. Thus, targeting of downstream transcriptional mediators may be a useful
therapeutic approach in attenuating cardiac fibrosis. Here, we discuss some of
the transcription factors that may regulate EndMT-mediated cardiac fibrosis and
their involvement in type 2 diabetes.
PMID- 28686849
TI - Lack of association between urotensin-II (UTS2) gene polymorphisms (Thr21Met and
Ser89Asn) and migraine.
AB - Migraine is a common neurovascular brain disorder with heterogeneous clinical
presentation, including recurrent headache attacks. The pathophysiology of
migraine is complex, and a number of genomic regions have been associated with
the development of migraine. In this study, we analyzed the allele and genotype
frequencies of the urotensin-II gene (UTS2) polymorphisms, Thr21Met and Ser89Asn,
among Turkish patients with migraine. A total of 146 patients with migraine (14
with aura [MA group] and 132 without aura [MO group]) were genotyped for Thr21Met
and Ser89Asn polymorphisms and compared with 154 age- and sex-matched healthy
controls. The UTS2 gene polymorphisms were analyzed by polymerase chain reaction
restriction fragment length polymorphism (PCR-RFLP). No significant differences
were observed in allele and genotype frequencies for Thr21Met and Ser89Asn
polymorphisms between the patients with migraine and control group. Similarly, we
did not observe significant differences in allele and genotype frequencies
between MA and MO and control group. Moreover, the haplotype analysis showed no
association between UTS2 gene haplotypes (MN, MS, TN, and TS) and migraine. In
summary, Thr21Met and Ser89Asn polymorphisms of the UTS2 gene are not risk
factors for migraine in our sample of Turkish migraine patients.
PMID- 28686850
TI - The effect of metformin treatment on endoplasmic reticulum (ER) stress induced by
status epilepticus (SE) via the PERK-eIF2alpha-CHOP pathway.
AB - Status epilepticus (SE) is defined as continuous seizure activity lasting more
than 5 minutes. It results in neuronal cell death, mediated by endoplasmic
reticulum (ER) stress response. Previously, metformin demonstrated
neuroprotective effects in primary cortical neurons. In this study, we analyzed
the effect of metformin on ER stress via the pro-apoptotic protein kinase RNA
like endoplasmic reticulum kinase (PERK)-eukaryotic initiation factor 2alpha
(eIF2alpha)-C/EBP homologous protein (CHOP) pathway. SE was induced in rats by
pentylenetetrazole. Following SE, the rats were treated with salubrinal,
GSK2656157, or metformin. In a control group (normal saline) SE was not induced.
CHOP, eIF2alpha, and PERK expression was determined by Western blot; apoptosis
was analyzed by TUNEL assay. CHOP expression was significantly increased at 6 and
24 hours following SE. At both time points, eIF2alpha and PERK levels were also
increased. At 6 hours, CHOP expression was significantly reduced in salubrinal,
GSK2656157 and metformin groups versus SE group. eIF2alpha and PERK levels were
decreased in metformin compared to SE group. eIF2alpha expression was markedly
decreased in salubrinal versus SE group, while PERK expression was markedly
reduced in GSK2656157 versus SE group. At 6 and 24 hours, the apoptosis rate was
significantly increased in SE versus control group, while it was significantly
reduced in salubrinal, GSK2656157, and metformin groups compared to SE group. The
apoptosis rate also decreased in salubrinal group at 24 hours, although not to
the extent observed in metformin group. Overall, CHOP expression and apoptosis
induced by SE in rats were reduced with metformin. Further studies are required
to evaluate the clinical relevance of metformin for patients with SE.
PMID- 28686851
TI - Characterization of Brown Adipose-Like Tissue in Trauma-Induced Heterotopic
Ossification in Humans.
AB - Heterotopic ossification (HO), the abnormal formation of bone within soft
tissues, is a major complication after severe trauma or amputation. Transient
brown adipocytes have been shown to be a critical regulator of this process in a
mouse model of HO. In this study, we evaluated the presence of brown fat within
human HO lesions. Most of the excised tissue samples displayed histological
characteristics of bone, fibroproliferative cells, blood vessels, and adipose
tissue. Immunohistochemical analysis revealed extensive expression of uncoupling
protein 1 (UCP1), a definitive marker of brown adipocytes, within HO-containing
tissues but not normal tissues. As seen in the brown adipocytes observed during
HO in the mouse, these UCP1+ cells also expressed the peroxisome proliferator
activated receptor gamma coactivator 1alpha. However, further characterization
showed these cells, like their mouse counterparts, did not express PR domain
containing protein 16, a key factor present in brown adipocytes found in depots.
Nor did they express factors present in beige adipocytes. These results identify
a population of UCP1+ cells within human tissue undergoing HO that do not
entirely resemble either classic brown or beige adipocytes, but rather a
specialized form of brown adipocyte-like cells, which have a unique function.
These cells may offer a new target to prevent this unwanted bone.
PMID- 28686852
TI - Integrated meta-omic analyses of the gastrointestinal tract microbiome in
patients undergoing allogeneic hematopoietic stem cell transplantation.
AB - In patients undergoing allogeneic hematopoietic stem cell transplantation (allo
HSCT), treatment-induced changes to the gastrointestinal tract (GIT) microbiome
have been linked to adverse outcomes, most notably graft-versus-host disease
(GvHD). However, it is presently unknown whether this relationship is causal or
consequential. Here, we performed an integrated meta-omic analysis to probe
deeper into the GIT microbiome changes during allo-HSCT and its accompanying
treatments. We used 16S and 18S rRNA gene amplicon sequencing to resolve archaea,
bacteria, and eukaryotes within the GIT microbiomes of 16 patients undergoing
allo-HSCT for the treatment of hematologic malignancies. These results revealed a
major shift in the GIT microbiome after allo-HSCT including a marked reduction in
bacterial diversity, accompanied by only limited changes in eukaryotes and
archaea. An integrated analysis of metagenomic and metatranscriptomic data was
performed on samples collected from a patient before and after allo-HSCT for
acute myeloid leukemia. This patient developed severe GvHD, leading to death 9
months after allo-HSCT. In addition to drastically decreased bacterial diversity,
the post-treatment microbiome showed a higher overall number and higher
expression levels of antibiotic resistance genes (ARGs). One specific Escherichia
coli strain causing a paravertebral abscess was linked to GIT dysbiosis,
suggesting loss of intestinal barrier integrity. The apparent selection for
bacteria expressing ARGs suggests that prophylactic antibiotic administration may
adversely affect the overall treatment outcome. We therefore assert that such
analyses including information about the selection of pathogenic bacteria
expressing ARGs may assist clinicians in "personalizing" regimens for individual
patients to improve overall outcomes.
PMID- 28686853
TI - WDR26 Haploinsufficiency Causes a Recognizable Syndrome of Intellectual
Disability, Seizures, Abnormal Gait, and Distinctive Facial Features.
AB - We report 15 individuals with de novo pathogenic variants in WDR26. Eleven of the
individuals carry loss-of-function mutations, and four harbor missense
substitutions. These 15 individuals comprise ten females and five males, and all
have intellectual disability with delayed speech, a history of febrile and/or non
febrile seizures, and a wide-based, spastic, and/or stiff-legged gait. These
subjects share a set of common facial features that include a prominent maxilla
and upper lip that readily reveal the upper gingiva, widely spaced teeth, and a
broad nasal tip. Together, these features comprise a recognizable facial
phenotype. We compared these features with those of chromosome 1q41q42
microdeletion syndrome, which typically contains WDR26, and noted that clinical
features are consistent between the two subsets, suggesting that
haploinsufficiency of WDR26 contributes to the pathology of 1q41q42 microdeletion
syndrome. Consistent with this, WDR26 loss-of-function single-nucleotide
mutations identified in these subjects lead to nonsense-mediated decay with
subsequent reduction of RNA expression and protein levels. We derived a
structural model of WDR26 and note that missense variants identified in these
individuals localize to highly conserved residues of this WD-40-repeat-containing
protein. Given that WDR26 mutations have been identified in ~1 in 2,000 of
subjects in our clinical cohorts and that WDR26 might be poorly annotated in
exome variant-interpretation pipelines, we would anticipate that this disorder
could be more common than currently appreciated.
PMID- 28686854
TI - REST Final-Exon-Truncating Mutations Cause Hereditary Gingival Fibromatosis.
AB - Hereditary gingival fibromatosis (HGF) is the most common genetic form of
gingival fibromatosis that develops as a slowly progressive, benign, localized or
generalized enlargement of keratinized gingiva. HGF is a genetically
heterogeneous disorder and can be transmitted either as an autosomal-dominant or
autosomal-recessive trait or appear sporadically. To date, four loci (2p22.1,
2p23.3-p22.3, 5q13-q22, and 11p15) have been mapped to autosomes and one gene
(SOS1) has been associated with the HGF trait observed to segregate in a dominant
inheritance pattern. Here we report 11 individuals with HGF from three unrelated
families. Whole-exome sequencing (WES) revealed three different truncating
mutations including two frameshifts and one nonsense variant in RE1-silencing
transcription factor (REST) in the probands from all families and further genetic
and genomic analyses confirmed the WES-identified findings. REST is a
transcriptional repressor that is expressed throughout the body; it has different
roles in different cellular contexts, such as oncogenic and tumor-suppressor
functions and hematopoietic and cardiac differentiation. Here we show the
consequences of germline final-exon-truncating mutations in REST for organismal
development and the association with the HGF phenotype.
PMID- 28686855
TI - Large-Scale Identification of Common Trait and Disease Variants Affecting Gene
Expression.
PMID- 28686857
TI - Integrative Genetic and Epigenetic Analysis Uncovers Regulatory Mechanisms of
Autoimmune Disease.
AB - Genome-wide association studies in autoimmune and inflammatory diseases (AID)
have uncovered hundreds of loci mediating risk. These associations are
preferentially located in non-coding DNA regions and in particular in tissue
specific DNase I hypersensitivity sites (DHSs). While these analyses clearly
demonstrate the overall enrichment of disease risk alleles on gene regulatory
regions, they are not designed to identify individual regulatory regions
mediating risk or the genes under their control, and thus uncover the specific
molecular events driving disease risk. To do so we have departed from standard
practice by identifying regulatory regions which replicate across samples and
connect them to the genes they control through robust re-analysis of public data.
We find significant evidence of regulatory potential in 78/301 (26%) risk loci
across nine autoimmune and inflammatory diseases, and we find that individual
genes are targeted by these effects in 53/78 (68%) of these. Thus, we are able to
generate testable mechanistic hypotheses of the molecular changes that drive
disease risk.
PMID- 28686856
TI - 10 Years of GWAS Discovery: Biology, Function, and Translation.
AB - Application of the experimental design of genome-wide association studies (GWASs)
is now 10 years old (young), and here we review the remarkable range of
discoveries it has facilitated in population and complex-trait genetics, the
biology of diseases, and translation toward new therapeutics. We predict the
likely discoveries in the next 10 years, when GWASs will be based on millions of
samples with array data imputed to a large fully sequenced reference panel and on
hundreds of thousands of samples with whole-genome sequencing data.
PMID- 28686859
TI - The aCCR(2)ual of M2 Macrophages Provides Some Breathing Room.
AB - Lung tissue can robustly regenerate functional alveolar units after injury, but
the mechanisms are unknown. Lechner et al. (2017) in this issue of Cell Stem Cell
demonstrate that lung regeneration is facilitated by bone-marrow-derived myeloid
cells that are recruited to the lung through a CCL2-CCR2 chemokine axis and by IL
13 expressing innate lymphoid cells.
PMID- 28686858
TI - A Pentanucleotide ATTTC Repeat Insertion in the Non-coding Region of DAB1,
Mapping to SCA37, Causes Spinocerebellar Ataxia.
AB - Advances in human genetics in recent years have largely been driven by next
generation sequencing (NGS); however, the discovery of disease-related gene
mutations has been biased toward the exome because the large and very repetitive
regions that characterize the non-coding genome remain difficult to reach by that
technology. For autosomal-dominant spinocerebellar ataxias (SCAs), 28 genes have
been identified, but only five SCAs originate from non-coding mutations. Over
half of SCA-affected families, however, remain without a genetic diagnosis. We
used genome-wide linkage analysis, NGS, and repeat analysis to identify an
(ATTTC)n insertion in a polymorphic ATTTT repeat in DAB1 in chromosomal region
1p32.2 as the cause of autosomal-dominant SCA; this region has been previously
linked to SCA37. The non-pathogenic and pathogenic alleles have the
configurations [(ATTTT)7-400] and [(ATTTT)60-79(ATTTC)31-75(ATTTT)58-90],
respectively. (ATTTC)n insertions are present on a distinct haplotype and show an
inverse correlation between size and age of onset. In the DAB1-oriented strand,
(ATTTC)n is located in 5' UTR introns of cerebellar-specific transcripts arising
mostly during human fetal brain development from the usage of alternative
promoters, but it is maintained in the adult cerebellum. Overexpression of the
transfected (ATTTC)58 insertion, but not (ATTTT)n, leads to abnormal nuclear RNA
accumulation. Zebrafish embryos injected with RNA of the (AUUUC)58 insertion, but
not (AUUUU)n, showed lethal developmental malformations. Together, these results
establish an unstable repeat insertion in DAB1 as a cause of cerebellar
degeneration; on the basis of the genetic and phenotypic evidence, we propose
this mutation as the molecular basis for SCA37.
PMID- 28686861
TI - Generation of Human Hair Cells In Vitro: Is It All about How the Wnt Blows?
AB - Screening for small molecules or drugs that can protect or restore mechanosensory
hair cells has been hampered by limited cell numbers. In Nature Biotechnology,
Koehler et al. (2017) have developed a human organoid-based approach using basic
developmental principles to generate large numbers of bonafide hair cells in
vitro.
PMID- 28686860
TI - Muscle Stem Cells Undergo Extensive Clonal Drift during Tissue Growth via Meox1
Mediated Induction of G2 Cell-Cycle Arrest.
AB - Organ growth requires a careful balance between stem cell self-renewal and
lineage commitment to ensure proper tissue expansion. The cellular and molecular
mechanisms that mediate this balance are unresolved in most organs, including
skeletal muscle. Here we identify a long-lived stem cell pool that mediates
growth of the zebrafish myotome. This population exhibits extensive clonal drift,
shifting from random deployment of stem cells during development to reliance on a
small number of dominant clones to fuel the vast majority of muscle growth. This
clonal drift requires Meox1, a homeobox protein that directly inhibits the cell
cycle checkpoint gene ccnb1. Meox1 initiates G2 cell-cycle arrest within muscle
stem cells, and disrupting this G2 arrest causes premature lineage commitment and
the resulting defects in muscle growth. These findings reveal that distinct
regulatory mechanisms orchestrate stem cell dynamics during organ growth, beyond
the G0/G1 cell-cycle inhibition traditionally associated with maintaining tissue
resident stem cells.
PMID- 28686862
TI - Making HSCs on Demand: Looking Ahead.
AB - George Daley and Shahin Rafii's groups recently generated multilineage, serially
engrafting hematopoietic stem cells (HSCs) from human pluripotent stem cells and
endothelial cells, respectively, achieving an important research milestone for
the field. We asked some experts in the field to reflect on the broader
implications of these findings.
PMID- 28686864
TI - Lack of Immune Response to Differentiated Cells Derived from Syngeneic Induced
Pluripotent Stem Cells.
PMID- 28686863
TI - The Evolving Roles of Human iPSC-Derived Cardiomyocytes in Drug Safety and
Discovery.
AB - Nonclinical studies of drug effects with human induced pluripotent stem cell
derived cardiomyocytes (hiPSC-CMs) provide new possibilities for evaluating drug
safety and efficacy. The Comprehensive In Vitro Proarrhythmia Assay (CiPA)
paradigm provides lessons from the cardiac field that also apply to drug studies
with other stem cell-based assays.
PMID- 28686865
TI - Lineage Tracing: Papers and Progress.
AB - This i3 is a data visualization based on the Cell Stem Cell tenth anniversary
theme of lineage tracing. Using Scopus citations of Cell Stem Cell research
papers, it illustrates both the evolution of the stem cell field and the way new
research builds on work that came before. Users can navigate the graphic and the
represented papers by stem cell type, organism, and author online at
cell.com/i3/cell-stem-cell/lineage. To view this SnapShot, open or download the
PDF.
PMID- 28686866
TI - Direct Neuronal Reprogramming: Achievements, Hurdles, and New Roads to Success.
AB - The ability to directly reprogram mature cells to alternative fates challenges
concepts of how cell identities are maintained, erased, and acquired. Recent
advances in understanding and overcoming hurdles to direct neuronal conversion
have provided new insights into mechanisms that maintain cell identity programs
and have enabled high efficiency reprogramming in vivo. We discuss key cell
intrinsic molecular and metabolic constraints that influence the establishment of
a new identity as well as environmental inputs from injured brains that favor or
harm the conversion process. Finally, we outline the challenges ahead with a
particular focus on direct neuronal reprogramming in vivo.
PMID- 28686867
TI - Expanding the Tissue Toolbox: Deriving Colon Tissue from Human Pluripotent Stem
Cells.
AB - Organoid technology holds great potential for disease modeling and regenerative
medicine. In this issue of Cell Stem Cell, Munera et al. (2017) establish the
generation of pluripotent stem cell-derived colon organoids that upon
transplantation in mice, resembling human colon to a large extent, opening up
avenues to study disease pathogenesis in human colon tissue.
PMID- 28686868
TI - Stem Cells: All that Is Solid Melts into Air.
AB - The intestinal epithelium displays great resilience, as several cell populations
can replenish the stem cell pool upon damage. Two studies in Cell Stem Cell
extend this capacity to enteroendocrine cells, addressing the molecular basis
underlying cellular plasticity observed in the intestine and the identities of
putative reserve stem cells.
PMID- 28686869
TI - Modeling the Glomerular Filtration Barrier: Are You Kidney-ing Me?
AB - Podocyte depletion drives kidney disease and kidney failure progression, but
podocyte complexity at the glomerular filtration barrier is difficult to model in
vitro. In Nature Biomedical Engineering, Musah et al. (2017) developed a
multifluidic device with iPS-derived podocytes mimicking a functional glomerular
filtration barrier that elevates standards for modeling glomerular diseases.
PMID- 28686871
TI - Retinoic Acid Puts Hematopoietic Stem Cells Back To Sleep.
AB - Dormant hematopoietic stem cells (dHSCs) display superior serial reconstitution
capacity compared to active HSCs, although their role in normal hematopoiesis has
not been thoroughly investigated. Recently in Cell, Cabezas-Wallscheid et al.
(2017) demonstrate involvement of retinoic acid signaling in murine dHSCs for
preservation of the HSC pool.
PMID- 28686872
TI - Rad52, Maestro of Inverse Strand Exchange.
AB - In this issue of Molecular Cell, Mazina et al. (2017) describe how the Rad52
protein mediates RNA-dependent DNA double-strand break repair via inverse strand
exchange. This finding sheds light on how eukaryotes utilize RNA to repair
chromosome breaks.
PMID- 28686873
TI - Noncanonical Mismatch Repair as a Source of Genomic Instability in Human Cells.
PMID- 28686870
TI - Intestinal Enteroendocrine Lineage Cells Possess Homeostatic and Injury-Inducible
Stem Cell Activity.
AB - Several cell populations have been reported to possess intestinal stem cell (ISC)
activity during homeostasis and injury-induced regeneration. Here, we explored
inter-relationships between putative mouse ISC populations by comparative RNA
sequencing (RNA-seq). The transcriptomes of multiple cycling ISC populations
closely resembled Lgr5+ ISCs, the most well-defined ISC pool, but Bmi1-GFP+ cells
were distinct and enriched for enteroendocrine (EE) markers, including Prox1.
Prox1-GFP+ cells exhibited sustained clonogenic growth in vitro, and lineage
tracing of Prox1+ cells revealed long-lived clones during homeostasis and after
radiation-induced injury in vivo. Single-cell mRNA-seq revealed two subsets of
Prox1-GFP+ cells, one of which resembled mature EE cells while the other
displayed low-level EE gene expression but co-expressed tuft cell markers, Lgr5
and Ascl2, reminiscent of label-retaining secretory progenitors. Our data suggest
that the EE lineage, including mature EE cells, comprises a reservoir of
homeostatic and injury-inducible ISCs, extending our understanding of cellular
plasticity and stemness.
PMID- 28686874
TI - Telomere Protection by TPP1/POT1 Requires Tethering to TIN2.
PMID- 28686877
TI - Editorial Comment.
PMID- 28686875
TI - Subtractional Heterogeneity: A Crucial Step toward Defining Specialized
Ribosomes.
AB - In this issue of Molecular Cell, Shi et al. (2017) identify translating ribosomes
which lack specific proteins and associate with specific classes of mRNAs. This
challenges the popular conception of "the ribosome" as a homogeneous, monolithic
molecular machine.
PMID- 28686878
TI - Current indication for hematopoietic cell transplantation in adults.
AB - With advances in transplantation technology and supportive care practices,
hematopoietic cell transplantation (HCT) has become relatively safer and the
applicability of HCT continues to expand. However, appropriate selection of
transplant candidates remains challenging. Identifying adult patients who may
benefit from HCT involves consideration of patient and disease factors, including
overall health, prior therapies, age, comorbidity, and disease/disease risk. The
eligibility of transplants should be decided on a case by case basis, based upon
a risk-benefit assessment. The advent of the tools for assessing patient factors
such as HCT-specific comorbidity index and disease factors such as disease risk
index serve as assets for the decision-making process. Besides those approaches,
psychosocial assessment to know the candidates' personalities and related issues
are crucial in order to maximize patients' participation in their own care and to
lay the foundation for a successful return to their personal and professional
life after HCT.
PMID- 28686879
TI - Hematopoietic stem cell transplantation in qatar: One-year anniversary.
AB - Hematopoietic stem cell transplantation (HSCT) offers potentially curative
therapy for many hematologic and nonhematologic conditions. As a successful
outcome of Qatar's National Cancer Strategy, the HSCT program was started in the
National Center for Cancer Care and Research (NCCCR) in October 2015. The HSCT
program in NCCCR is the only transplant program in Qatar and self-sufficient with
all three core components: the stem cell collection facility, the stem cell
processing facility, and the clinical program, which are locally available at
Hamad Medical Corporation. In this paper, we report on the outcomes of the first
16 patients who underwent autologous stem cell transplantations (ASCTs) in our
center. A total of 17 ASCT have been performed for 16 adult (>=14years) patients.
Thirteen of the 16 patients were eligible for disease evaluation at Day 100 post
ASCT. Among these patients, the overall response rate on Day 100 was 92%
(complete remission, 61%; very good partial remission/partial remission, 31%) and
stable disease occurred in 6%. The procedure was very well tolerated by all
patients. At the time of writing this report, all patients are alive; however,
one patient (6%) had disease relapse. The Day 100 post-ASCT nonrelapse mortality
rate was 0%. Launching the HSCT program represents a historic milestone in the
development of the health-care sector in Qatar. The 1st year of this program was
very fruitful with the accomplishment of 17 successful transplants. We are in the
process of starting the allogenic HSCT early next year. This would represent the
next significant milestone for cancer care in Qatar.
PMID- 28686880
TI - Chicken mannose binding lectin has antiviral activity towards infectious
bronchitis virus.
AB - Mannose binding lectin (MBL) is a collagenous C-type lectin, which plays an
important role in innate immunity. It can bind to carbohydrates on the surface of
a wide range of pathogens, including viruses. Here we studied the antiviral
effect of recombinant chicken (rc)MBL against Infectious Bronchitis Virus (IBV),
a highly contagious coronavirus of chicken. rcMBL inhibited in a dose-dependent
manner the infection of BHK-21 cells by IBV-Beaudette, as detected by
immunofluorescence staining of viral proteins and qPCR. ELISA and negative
staining electron microscopy showed that rcMBL bound directly to IBV, resulting
in the aggregation of viral particles. Furthermore, we demonstrated that MBL
bound specifically to the spike S1 protein of IBV which mediates viral
attachment. This subsequently blocked the attachment of S1 to IBV-susceptible
cells in chicken tracheal tissues as shown in protein histochemistry. Taken
together, rcMBL exhibits antiviral activity against IBV, based on a direct
interaction with IBV virions.
PMID- 28686881
TI - Cross-classified multilevel models for severity of commercial motor vehicle
crashes considering heterogeneity among companies and regions.
AB - This study analyzes 86,622 commercial motor vehicle (CMV) crashes (large truck,
bus and taxi crashes) in South Korea from 2010 to 2014. The analysis recognizes
the hierarchical structure of the factors affecting CMV crashes by examining
eight factors related to individual crashes and six additional upper level
factors organized in two non-nested groups (company level and regional level
factors). The study considers four different crash severities (fatal, major,
minor, and no injury). The company level factors reflect selected characteristics
of 1,875 CMV companies, and the regional level factors reflect selected
characteristics of 230 municipalities. The study develops a single-level ordinary
ordered logit model, two conventional multilevel ordered logit models, and a
cross-classified multilevel ordered logit model (CCMM). As the study develops
each of these four models for large trucks, buses and taxis, 12 different
statistical models are analyzed. The CCMM outperforms the other models in two
important ways: 1) the CCMM avoids the type I statistical errors that tend to
occur when analyzing hierarchical data with single-level models; and 2) the CCMM
can analyze two non-nested groups simultaneously. Statistically significant
factors include taxi company's type of vehicle ownership and municipality's level
of transportation infrastructure budget. An improved understanding of CMV related
crashes should contribute to the development of safety countermeasures to reduce
the number and severity of CMV related crashes.
PMID- 28686882
TI - Distributed practice can boost evaluative conditioning by increasing memory for
the stimulus pairs.
AB - When presenting a neutral stimulus (CS) in close temporal and spatial proximity
to a positive or negative stimulus (US) the former is often observed to adopt the
valence of the latter, a phenomenon named evaluative conditioning (EC). It is
already well established that under most conditions, contingency awareness is
important for an EC effect to occur. In addition to that, some findings suggest
that awareness of the stimulus pairs is not only relevant during the learning
phase, but that it is also relevant whether memory for the pairings is still
available during the measurement phase. As previous research has shown that
memory is better after temporally distributed than after contiguous (massed)
repetitions, it seems plausible that also EC effects are moderated by distributed
practice manipulations. This was tested in the current studies. In two
experiments with successful distributed practice manipulations on memory, we show
that also the magnitude of the EC effect was larger for pairs learned under
spaced compared to massed conditions. Both effects, on memory and on EC, are
found after a within-participant and after a between-participant manipulation.
However, we did not find significant differences in the EC effect for different
conditions of spaced practice. These findings are in line with the assumption
that EC is based on similar processes as memory for the pairings.
PMID- 28686883
TI - Does contingency in adults' responding influence 12-month-old infants' social
referencing?
AB - In two experiments we examined the influence of contingent versus non-contingent
responding on infant social referencing behavior. EXPERIMENT 1: Forty 12-month
old infants were exposed to an ambiguous toy in a social referencing situation.
In one condition an unfamiliar adult who in a previous play situation had
responded contingently to the infant's looks gave the infant positive information
about the toy. In the other condition an unfamiliar adult who previously had not
responded contingently delivered the positive information. EXPERIMENT 2: Forty
eight 12-month-old infants participated in Experiment 2. In this experiment it
was examined whether the familiarity of the adult influences infants' reactions
to contingency in responding. In one condition a parent who previously had
responded contingently to the infant's looks provided positive information about
the ambiguous toy, and in the other condition a parent who previously had not
responded contingently provided the positive information. The infants looked more
at the contingent experimenter in Experimenter 1, and also played more with the
toy after receiving positive information from the contingent experimenter. No
differences in looking at the parent and in playing with the toy were found in
Experiment 2. The results indicate that contingency in responding, as well as the
familiarity of the adult, influence infants' social referencing behavior.
PMID- 28686884
TI - 10B/11B isotopic ratio and atomic composition of boron carbide: Determination by
proton induced gamma-ray emission and proton elastic backscattering spectrometry.
AB - The 10B/11B isotopic ratio and the atomic composition of boron carbide, an
important non-metallic ceramic, have been determined non-destructively by the
particle induced gamma-ray emission (PIGE) and elastic backscattering
spectrometry (EBS) techniques with proton beams. The analysis has been performed
on powder as well as sintered ceramics containing boron in natural or 10B
enriched composition. The PIGE technique, performed at a 4.0-4.2MeV proton
energy, utilizes the 10B(p,alphagamma)7Be, 10B(p,p'gamma)10B and 11B(p,
p'gamma)11B nuclear reactions for (a) the isotopic analysis of boron and (b) the
determination of total boron, and the 13C(p,p'gamma)13C nuclear reaction for the
determination of carbon. The irradiation conditions were optimized by determining
the thick targets yields of prompt gamma-rays, characteristic of these reactions,
in the 3.0-4.2MeV proton energy range. The quantitative analysis was performed by
comparison with standards taking into account the attenuation of gamma-rays in
the specimens. The uncertainty in the determination of the 10B/11B isotopic ratio
and the B/C atomic ratio is about 2% and about 5% respectively. The analysis by
EBS, on the other hand, involves the 10B(p,p)10B, 11B(p,p)11B and 12C(p,p)12C
elastic scatterings at the 2.0MeV proton energy. This method too yields
satisfactory results. Between the two, PIGE is the method of choice for bulk
analysis while EBS is useful in discerning compositional variations in surface
regions.
PMID- 28686885
TI - A radioactive material monitoring system using multiple gamma spectroscopy
detectors and centroid method.
AB - A radioactive material monitoring system, employing a passive detection technique
with multiple gamma spectroscopy detectors and the centroid method for use in
large areas, is presented. The system determines the location and the activity of
radioisotopes. The proposed system was designed and evaluated using Monte Carlo
simulations and experiments. In both simulation and experiment, calculated source
locations were well distinguished and the location was determined within less
than 1m range compared to the actual location. The calculated activity was
matched to the actual activity within an error of 5%.
PMID- 28686886
TI - Measurement of neutron spectra in a silicon filtered neutron beam using stilbene
detectors at the LVR-15 research reactor.
AB - A well-defined neutron spectrum is an essential tool for calibration and tests of
spectrometry and dosimetry detectors, and evaluation methods for spectra
processing. Many of the nowadays used neutron standards are calibrated against a
fission spectrum which has a rather smooth energy dependence. In recent time, at
the LVR-15 research reactor in Rez, an alternative approach was tested for the
needs of fast neutron spectrometry detector calibration. This process comprises
detector tests in a neutron beam, filtered by one meter of single-crystalline
silicon, which contains several significant peaks in the fast neutron energy
range. Tests in such neutron field can possibly reveal specific problems in the
deconvolution matrix of the detection system, which may stay hidden in fields
with a smooth structure and can provide a tool for a proper energy calibration.
Test with several stilbene scintillator crystals in two different beam
configurations supplemented by Monte-Carlo transport calculations have been
carried out. The results have shown a high level of agreement between the
experimental data and simulation, proving thus the accuracy of used deconvolution
matrix. The chosen approach can, thus, provide a well-defined neutron reference
field with a peaked structure for further tests of spectra evaluation methods and
scintillation detector energy calibration.
PMID- 28686887
TI - Can the exposure of Apis mellifera (Hymenoptera, Apiadae) larvae to a field
concentration of thiamethoxam affect newly emerged bees?
AB - The use of insecticides on crops can affect non-target insects, such as bees. In
addition to the adult bees, larvae can be exposed to the insecticide through
contaminated floral resources. Therefore, this study aimed to investigate the
possible effects of the exposure of A. mellifera larvae to a field concentration
of thiamethoxam (0.001 ng/MUL thiamethoxam) on larval and pupal survival and on
the percentage of adult emergence. Additionally, its cytotoxic effects on the
digestive cells of midgut, Malpighian tubules cells and Kenyon cells of the brain
of newly emerged A. mellifera bees were analyzed. The results showed that larval
exposure to this concentration of thiamethoxam did not influence larval and pupal
survival or the percentage of adult bee emergence. However, this exposure caused
ultra-structural alterations in the target and non-target organs of newly emerged
bees. The digestive cell of bees that were exposed to the insecticide exhibited a
basal labyrinth without long and thin channels and compromised mitochondria. In
Malpighian tubules cells, disorganized basal labyrinth, dilated mitochondria with
a deformed shape and a loss of cristae, and disorganized microvilli were
observed. The results showed that the exposed bees presented Kenyon cells with
alterations in the nucleus and mitochondria. These alterations indicate possible
tissue degeneration, demonstrating the cytotoxicity of thiamethoxam in the target
and non-target organs of newly emerged bees. Such results suggest cellular
organelle impairment that can compromise cellular function of the midgut cells,
Malpighian tubules cells and Kenyon cells, and, consequently, can compromise the
longevity of the bees of the whole colony.
PMID- 28686888
TI - Characterization of a polycyclic aromatic ring-hydroxylation dioxygenase from
Mycobacterium sp. NJS-P.
AB - Ring-hydroxylating dioxygenases (RHDs) play a critical role in the biodegradation
of polycyclic aromatic hydrocarbons (PAHs). In this study, genes pdoAB encoding a
dioxygenase capable of oxidizing various PAHs with up to five-ring benzo[a]pyrene
were cloned from Mycobacterium sp. NJS-P. The alpha-subunit of the PdoAB showed
99% and 93% identity to that from Mycobacterium sp. S65 and Mycobacterium sp.
py136, respectively. An Escherichia coli expression experiment revealed that the
enzyme is able to oxidize anthracene, phenanthrene, pyrene and benzo[a]pyrene,
but not to fluoranthene and benzo[a]anthracene. Furthermore, the results of in
silico analysis showed that PdoAB has a large substrate-binding pocket satisfying
for accommodation of HMW PAHs, and suggested that the binding energy of
intermolecular interaction may predict the substrate conversion of RHDs towards
HMW PAHs, especially those may have steric constraints on the substrate-binding
pocket, such as benzo[a]pyrene and benzo[a]anthracene.
PMID- 28686889
TI - Serpentine endophytic bacterium Pseudomonas azotoformans ASS1 accelerates
phytoremediation of soil metals under drought stress.
AB - This study evaluates the potential of serpentine endophytic bacterium to foster
phytoremediation efficiency of Trifolium arvense grown on multi-metal (Cu, Zn and
Ni) contaminated soils under drought stress. A drought resistant endophytic
bacterial strain ASS1 isolated from the leaves of Alyssum serpyllifolium grown in
serpentine soils was identified as Pseudomonas azotoformans based on biochemical
tests and partial 16S rRNA gene sequencing. P. azotoformans ASS1 possessed
abiotic stress resistance (heavy metals, drought, salinity, antibiotics and
extreme temperature) and plant growth promoting (PGP) properties (phosphate
solubilization, nitrogen fixation, production of 1-aminocyclopropane-1
carboxylate deaminase, siderophore and ammonia). Inoculation of T. arvense with
ASS1 considerably increased the plant biomass and leaf relative water content in
both roll towel assay and pot experiments in the absence and presence of drought
stress (DS). In the pot experiments, ASS1 greatly enhanced chlorophyll content,
catalase, peroxidase, superoxide dismutase activities, and proline content (only
in the absence of drought) in plant leaves, whereas they decreased the
concentrations of malondialdehyde. Irrespective of water stress, ASS1
significantly improved accumulation, total removal, bio-concentration factor and
biological accumulation coefficient of metals (Cu, Zn and Ni), while decreased
translocation factors of Cu. The effective colonization and survival in the
rhizosphere and tissue interior assured improved plant growth and successful
metal phytoremediation under DS. These results demonstrate the potential of
serpentine endophytic bacterium ASS1 for protecting plants against abiotic
stresses and helping plants to thrive in semiarid ecosystems and accelerate
phytoremediation process in metal polluted soils.
PMID- 28686890
TI - Assessing the use of delta18O in phosphate as a tracer for catchment phosphorus
sources.
AB - Procedures for source apportionment of nutrients transported in rivers and
streams are often uncertain and difficult to validate. In this study, we
investigated if the oxygen isotope ratios in stream dissolved phosphate
(delta18OP) can be used to distinguish between the phosphorus (P) originating
from agricultural runoff and from rural sewage, at different periods of the year.
Water was collected from septic tanks, drainage wells and the stream outlet in a
small (7.3 km2) agricultural catchment to capture variations in the isotope
signature at different flow events. The delta18OP signature in septic tank
effluent (+13.2 to +14.50/00) was significantly different from that in drainage
water (+9.0 to +15.70/00). Four different septic tanks had surprisingly similar
isotope signature when 24 h composite samples were collected. Most of the water
samples were not in oxygen isotope equilibrium. In three drainage wells, the
delta18OP signature varied from +7.8 up to +15.70/00 with higher values in
periods with a larger contribution of superficial streamflow generation. A
rainfall soon after manure had been spread resulted in a delta18OP of 15.70/00 in
a drainage well, and was also reflected in a similar value at the catchment
outlet. This implies that the source isotope signal may be conserved during
moderate or high flows. A three end-member model including the geological
background would be a useful start to quantify the P contribution from diverse
sources. Temporal differences in biological activity and the predominant
transport pathways through soil profiles must be considered along with
information about fertilisation. In combination with hydrological modelling of
water pathways, this may considerably improve our understanding of catchment P
losses.
PMID- 28686891
TI - Comparison of aerosol and cloud condensation nuclei between wet and dry seasons
in Guangzhou, southern China.
AB - Cloud condensation nuclei (CCN), condensation nuclei (CN) and aerosol chemical
composition were measured simultaneously at an urban site of Guangzhou from July
to August 2015 and in January 2016, and the seasonal variations of aerosol
activated fractions (NCCN/NCN) as well as their relevant influence factors were
further studied accordingly. NCN is generally higher in winter (dry season),
whereas NCCN and NCCN/NCN are mostly higher in summer (wet season) instead. In
particular, NCCN and NCCN/NCN are much lower at smaller supersaturation levels
(SS<0.2) in winter. In spite of similar diurnal variations for NCCN and NCN,
NCCN/NCN indicates an opposite tendency, relatively lower at midday, dusk and
before midnight. Other than the size of particles as well as their chemical
composition, some other factors, such as mass, gas precursors, pollutant
transportation, meteorological conditions, etc., also contribute to the
variations of NCCN and NCCN/NCN. Particles from the local source or local-oceanic
combination source cast influence on CN and CCN significantly, while the
pollutants originating from and crossing over distant polluted areas contribute
largely to CCN/CN. NCN and NCCN are relatively higher under pollution-free
conditions in summertime and polluted conditions in wintertime, but NCCN/NCN is
just the opposite. On various polluted conditions, aerosol CCN activities are
greatly discrepant between summer and winter, especially during mist or heavy
haze periods. The results imply that anthropogenic pollutants exert critical
impacts on aerosol CCN activation.
PMID- 28686892
TI - Anaerobic oxidation of methane by aerobic methanotrophs in sub-Arctic lake
sediments.
AB - Anaerobic oxidation of methane (AOM) is a biological process that plays an
important role in reducing the CH4 emissions from a wide range of ecosystems.
Arctic and sub-Arctic lakes are recognized as significant contributors to global
methane (CH4) emission, since CH4 production is increasing as permafrost thaws
and provides fuels for methanogenesis. Methanotrophy, including AOM, is critical
to reducing CH4 emissions. The identity, activity, and metabolic processes of
anaerobic methane oxidizers are poorly understood, yet this information is
critical to understanding CH4 cycling and ultimately to predicting future CH4
emissions. This study sought to identify the microorganisms involved in AOM in
sub-Arctic lake sediments using DNA- and phospholipid-fatty acid (PLFA)- based
stable isotope probing. Results indicated that aerobic methanotrophs belonging to
the genus Methylobacter assimilate carbon from CH4, either directly or
indirectly. Other organisms that were found, in minor proportions, to assimilate
CH4-derived carbon were methylotrophs and iron reducers, which might indicate the
flow of CH4-derived carbon from anaerobic methanotrophs into the broader
microbial community. While various other taxa have been reported in the
literature to anaerobically oxidize methane in various environments (e.g. ANME
type archaea and Methylomirabilis Oxyfera), this report directly suggest that
Methylobacter can perform this function, expanding our understanding of CH4
oxidation in anaerobic lake sediments.
PMID- 28686893
TI - A relationship in adrenal androgen levels between mothers and their children from
a dioxin-exposed region in Vietnam.
AB - Over the past decades, southern Vietnam has been burdened by dioxins from
contaminated herbicides sprayed during the Vietnam War. In a previous study, we
found that dioxin exposure decreased levels of salivary dehydroepiandrosterone
(DHEA), an adrenal androgen, in 3-year-old children. In present study, to assess
the relationship between adrenal hormones disruption in lactating mothers and in
children, we compared mother-child pairs from dioxin- and nondioxin-contaminated
regions. In 2010 and 2011, mother-child pairs from a dioxin hotspot region (n=37)
and a non-contaminated region (n=47) were recruited and donated breast milk and
serum samples for dioxin and steroid hormones determination. Mothers were 20
30years old and had given birth to their first child between 4 and 16weeks
previously. One year later, saliva samples were collected from the children.
Dioxin levels in breast milk were determined by gas chromatography/high
resolution mass spectrometry. Salivary DHEA, cortisol in children and
androstenedione (A-dione), estradiol, cortisol, and DHEA in maternal serum were
analyzed by liquid chromatography/tandem mass spectrometry. Concentrations of
dioxin congeners in the hotspot region were 2- to 5-fold higher than in samples
from the non-contaminated region. Salivary DHEA levels in children and serum A
dione levels in mothers were significantly higher in the hotspot region; no
difference was found in the levels of other hormones. Moreover, there was a
significant positive correlation between the elevated hormone levels in mothers
and children (r=0.62, p<0.001). Several dioxin congeners exhibited strong
significant dose-response relationships with salivary DHEA and serum A-dione
levels. Our findings suggest that dioxin disrupts adrenal androgens in mothers
and breastfeeding children through the same mechanism.
PMID- 28686894
TI - Identification of weathered multiple petroleum products in contaminated soils by
characterizing unresolved complex mixture hump in gas chromatograph data.
AB - A new method for identifying the petroleum products in contaminated soils is
presented, which characterizes the unresolved complex mixture (UCM) hump in the
baseline of gas chromatograph (GC) data. The UCM hump identified in soil data was
fitted to the Gaussian function, and characterized according to the time for the
maximum point (TUCM) and the width of the hump (w). Experimental results showed
that a UCM hump should be clearly observed in soils when contaminated with
petroleum, and that soils contaminated with kerosene, diesel, or some lubricating
oils estimated herein should present different characteristic values of TUCM and
w. Even though the environmental weathering of contaminated soils under
evaporative conditions might cause variations in these characteristic values,
they converged to specific constants depending on the product. The method could
also differentiate between multiple petroleum contaminants in soil. Feasibility
was evaluated using soils from a military oil storage site that was closed in
1970. The soil contaminants identified by the proposed method corresponded to the
historical storage records, suggesting that the UCM hump characterization method
could have strong potential in environmental forensics for differentiating
products in petroleum-contaminated soils.
PMID- 28686895
TI - Bioenergy generation and rhizodegradation as affected by microbial community
distribution in a coupled constructed wetland-microbial fuel cell system
associated with three macrophytes.
AB - Rhizodeposits excreted by various macrophytes might lead to the potential
discrepancy of microbial community distribution in constructed wetland coupled
with microbial fuel cell (CW-MFC), which has been considered as main factors for
the variations of bioelectricity generation during wastewater treatment. In this
study, CW-MFC has been associated with three macrophytes (J. effuses, T.
orientalis and S. validus) for domestic sewage treatment, also unplanted CW-MFC
was performed as a control system. Macrophyte T. orientalis and S. validus can
significantly strengthen the bioenergy output in CW-MFC. Highest current
(94.27mAm-2) and power densities (21.53mWm-2) were obtained in CW-MFC planted
with T. orientalis. Removal efficiencies of COD, NO3-N and NH3-N in CW-MFC
planted with S. validus was respectively 5.8%, 7.2%, and 23.9% higher than that
of unplanted system. Notably, the oxygen depletion in S. validus CW-MFC reactor
during the dark cycle was higher that of other reactors. Results of high
throughput sequencing analysis showed that higher biodiversity was observed in
rhizosphere than that of anode material, and the relative abundance of
Desulfobulbus sp. and Geobacter sp. has been apparently promoted in the samples
of rhizosphere. However, a higher relative abundance of electrochemically active
bacteria (Proteobacteria) was observed on the surface of anode electrode
material. In addition, microbes (Cytophagales, Clostridium sp., and Dechloromonas
sp., and so forth) found in rhizosphere show a capability to decompose refractory
contaminants. These contaminants and death roots in the upper part of wetland
could be oxidized to fat acids, which may be used as the electrons acceptors for
promoting the bioelectricity generation during wastewater treatment.
PMID- 28686896
TI - High cancer risks by exposure to PCDD/Fs in the neighborhood of an Integrated
Waste Management Facility.
AB - In 2014, we conducted a study aimed at screening the concentrations of
polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs), polychlorinated
biphenyls (PCBs) and various trace elements in air and soil samples collected in
an urban area of Sant Adria de Besos (Barcelona, Spain) in the vicinity of an
Integrated Waste Management Facility (IWMF). It consists of a mechanical
biological treatment plant (MBT) and an old municipal solid waste incinerator
(MSWI). Human health risks for the population living in the area were also
assessed. The most worrying result was the high cancer risks estimated for the
area (2.5*10-6). In March 2017, we have carried out a new survey to check if the
authorities had taken the necessary and urgent measures to reduce the
environmental concentrations of PCDD/Fs -and the human health risks- until
acceptable levels. Although the concentrations of PCDD/Fs in soils are currently
lower (mean value: 1.66 vs. 3.6ng WHO-TEQ/kg in 2014), they are still are notably
higher than those found near other MSWIs of Catalonia. In turn, the levels of
PCDD/Fs in air are even higher than in 2014 (mean value: 0.044 vs. 0.026pgWHO
TEQ/m3 in 2014), being also the highest detected in similar zones of Catalonia.
The current cancer risk due to PCDD/F exposure for the residents in the
neighborhood of the IWMF is 2.3*10-6, a worrying fact as the 10-6 threshold
continues to be exceeded.
PMID- 28686897
TI - Exploring uptake and biodistribution of polystyrene (nano)particles in zebrafish
embryos at different developmental stages.
AB - In ecotoxicology, it is continuously questioned whether (nano)particle exposure
results in particle uptake and subsequent biodistribution or if particles adsorb
to the epithelial layer only. To contribute to answering this question, we
investigated different uptake routes in zebrafish embryos and how they affect
particle uptake into organs and within whole organisms. This is addressed by
exposing three different life stages of the zebrafish embryo in order to cover
the following exposure routes: via chorion and dermal exposure; dermal exposure;
oral and dermal exposure. How different nanoparticle sizes affect uptake routes
was assessed by using polystyrene particles of 25, 50, 250 and 700nm. In our
experimental study, we showed that particle uptake in biota is restricted to oral
exposure, whereas the dermal route resulted in adsorption to the epidermis and
gills only. Ingestion followed by biodistribution was observed for the tested
particles of 25 and 50nm. The particles spread through the body and eventually
accumulated in specific organs and tissues such as the eyes. Particles larger
than 50nm were predominantly adsorbed onto the intestinal tract and outer
epidermis of zebrafish embryos. Embryos exposed to particles via both epidermis
and intestine showed highest uptake and eventually accumulated particles in the
eye, whereas uptake of particles via the chorion and epidermis resulted in
marginal uptake. Organ uptake and internal distribution should be monitored more
closely to provide more in depth information of the toxicity of particles.
PMID- 28686898
TI - Prenatal transfer of decabromodiphenyl ether (BDE-209) results in disruption of
the thyroid system and developmental toxicity in zebrafish offspring.
AB - Decabromodiphenyl ether (BDE-209) was one of most widely-used polybrominated
diphenyl ether (PBDE) flame retardants and is frequently detected in both abiotic
and biotic samples from environment. However, knowledge of its transgenerational
risks is limited. Here, 4-month-old zebrafish were exposed to various
concentrations of BDE-209 (0, 3, 30 or 300MUg/L) for 28days and spawned in clean
water without BDE-209. Concentrations of triiodothyronine (T3) and thyroxine (T4)
as well as expressions of genes involved in the hypothalamic-pituitary-thyroid
(HPT) axis were measured in offspring after exposure of adult zebrafish to BDE
209. BDE-209 was accumulated in adult fish and F1 eggs, which suggests transfer
of this compound from adult fish to their offspring. Exposure of BDE-209 to
parents resulted in developmental abnormalities in offspring and a significant
decrease in T4 concentrations in F1 larvae 120h post-fertilization (hpf).
Furthermore, expressions of several genes involved in the HPT axis were also
altered. Expressions of thyroid hormone receptor alpha (tr-alpha), thyrotropin
releasing hormone (trh), thyroid stimulating hormone beta (tsh-beta) and
deiodinase 1 (dio 1) were significantly down-regulated in F1 individuals, while
expressions of thyroid stimulating hormone receptor (tshr) and transthyretin
(ttr) were significantly up-regulated. These results suggest that exposure of
parent zebrafish to BDE-209 can cause developmental toxicity in offspring and
disruption of the thyroid endocrine system of offspring.
PMID- 28686899
TI - Ceanothane- and lupane-type triterpene esters from the roots of Hovenia dulcis
and their antiproliferative activity on HSC-T6 cells.
AB - Three ceanothane-type and three lupane-type triterpenoids, as well as three known
compounds, were isolated from the roots of Hovenia dulcis (Rhamnaceae), based on
LC-MS dereplication. The previously undescribed compounds were determined to be
27-O-protocatechuoyl-3-dehydroxyisoceanothanolic acid, 27-O-protocatechuoyl-3
dehydroxycolubrinic acid, 27-O-protocatechuoyl-3-dehydroxyepicolubrinic acid, 27
O-protocatechuoylbetulinic acid, 27-O-p-hydroxybenzoylbetulinic acid, and 27-O
syringoylbetulinic acid by 1D and 2D NMR spectroscopic and HR mass spectrometric
data analysis. The isolates were examined for their antiproliferative activity in
HSC-T6 hepatic stellate cells; compounds 1, 2, 3, and 6 showed IC50 values in the
range of 15-50 MUM.
PMID- 28686900
TI - Bioactive polyketides and 8,14-seco-ergosterol from fruiting bodies of the
ascomycete Daldinia childiae.
AB - Seven previously undescribed polyketides, namely childinins A-G, and one
previously undescribed 8,14-seco-ergosterol, namely childinasterone A, were
obtained from the fruiting bodies of Daldinia childiae. Their structures and
absolute configurations were established via extensive spectroscopic analyses,
single-crystal X-ray diffraction, and TDDFT/ECD calculations. Childinins A
represents the first example of natural product possessing a previously
undescribed 6H-naphtho[2,1-c]chromen-6-one scaffold. The single crystal X-ray
diffraction of childinasterone A unambiguously determined the absolute
configuration of a 8,14-seco-ergosterol skeleton. Childinins A, B, F and G (MIC90
54.9 MUg?mL-1) showed anti-bacterial activities. Childinasterone A showed
significant anti-NO activity (IC50 21.2 MUM) and weak activities against SMMC
7721, MCF-7 and SW480 cell lines.
PMID- 28686901
TI - Noncalssical multiscale modeling of ssDNA manipulation using a CNT-nanocarrier
based on AFM.
AB - Nanocarriers are useful tools in biological and medical research fields. In
nanomanipulation, a nondestructive and successful process can be achieved by
using nanocarriers. In this paper, a nonclassical multiscale approach has been
presented for modeling a single strand DNA (ssDNA) manipulation based on AFM. To
achieve a nondestructive nanomanipulation process, carbon nanotube (CNT) has been
used as a nanocarrier. AFM setup has been separated into a Micro field (MF) and a
Nano field (NF). The governing equations of the MF have been derived based on
Kirchhoff plate model and a modified couple stress theory. The NF has been
modeled by molecular dynamics (MD) method. A set of nanomanipulations has been
performed for the free ssDNA and the ssDNA inside the nanocarrier (shielded
ssDNA) on three types of substrates. The exerted forces on the free ssDNA and the
shielded ssDNA have been compared for manipulation on various substrates. The
results show that using the nanocarrier reduces the manipulation force
considerably. The results of RMSD as a general geometrical criterion have
illustrated that the maximum damage occurs on the golden substrate for free
ssDNA. Elongation and curvature criteria have been presented to investigate the
ssDNA deformation in detail. The elongation and curvature criteria have been
shown that using a nanocarrier is a good approach for a successful and
nondestructive nanomanipulation. Finally it can be concluded that the
manipulation process of free ssDNA on silicon substrate is successful as well as
the manipulation process of the shielded ssDNA on all three types of substrates.
PMID- 28686902
TI - Silk fibroin-coated PLGA dimpled microspheres for retarded release of
simvastatin.
AB - The surface physical features and chemical components of polymeric particles play
an important role in drug delivery systems. In this study, PLGA blank
microspheres and simvastatin-loaded PLGA microspheres with dimpled surface
structure were prepared by single emulsion-solvent evaporation method in the
absence of any additives. Subsequently, glutaraldehyde cross-linking was
optimized for silk fibroin coating on simvastatin-loaded PLGA dimpled
microspheres due to good solubility of simvastatin in alcohol. Furthermore,
simvastatin release kinetics was investigated for silk-coated or plain PLGA
dimpled microspheres. These drug carriers may have potential applications for
alveolar ridge preservation with local delivery of simvastatin.
PMID- 28686903
TI - Polysaccharide-coated liposomes by post-insertion of a hyaluronan-lipid
conjugate.
AB - Hyaluronan (MW: 1.5 MDa) was linked to a phospholipid (dipalmitoyl
phosphatidylethanolamine, DPPE) by an amidification procedure to obtain novel
macromolecules (HA-DPPE) able to coat liposomes. Liposomes made of dipalmitoyl
phosphatidylcholine and cholesterol (DPPC/Chol: 95/5 molar ratio), with a mean
size around 100nm, were incubated with HA-DPPE at 55 degrees C, allowing the
insertion of DPPE moieties in the liposomal bilayer and leading to hyaluronan
coated liposomes (HAsomes) as evidenced by several techniques including dynamic
light scattering and differential scanning calorimetry. The amount or HA-DPPE
coating liposomes was quantified by different methods among which capillary
electrophoresis and their stability in serum was finally compared to that of
plain liposomes. As a conclusion, we provide insight into the physico-chemical
characterization of HA-DPPE and of HAsomes demonstrating that easy coating of
phospholipid vesicles can be achieved by post-insertion of a lipid derivative of
hyaluronan. This approach represents an innovative strategy for coating vesicular
systems to confer them simultaneously with long circulation properties and
selective targeting towards HA-receptors.
PMID- 28686904
TI - Gender differences in susceptibility to schizophrenia: Potential implication of
neurosteroids.
AB - Past research has indicated gender differences in the clinical characteristics
and course of schizophrenia. In this study, we investigated whether gender
differences in the manifestation of schizophrenia are correlated with
neurosteroids, including dehydroepiandrosterone (DHEA), dehydroepiandrosterone
sulfate (DHEA-S), and pregnenolone. We further explored the potential
relationship between the aforementioned neurosteroids and psychopathology. We
recruited 65 schizophrenic patients (36 males and 29 females) and 103 healthy
control subjects (47 males and 56 females) and obtained blood samples from the
subjects in the morning while in a fasting state to determine the serum levels of
DHEA, DHEA-S, and pregnenolone. The psychopathology and mood symptoms of patients
with schizophrenia were evaluated using the Positive and Negative Syndrome Scale
(PANSS) and 17-item Hamilton Depression Rating Scale, respectively. Compared to
the male control subjects, male patients with schizophrenia had significantly
lower serum levels of DHEA and pregnenolone. In males with schizophrenia, the
serum levels of DHEA and DHEA-S were associated with the age of onset and the
duration of illness, while pregnenolone levels were associated with general
symptoms of the PANSS. However, none of the neurosteroid levels were different
between the female patients with schizophrenia and the female controls, and no
significant correlation between neurosteroid levels and psychopathology
evaluations was found among the schizophrenic females. Neurosteroids, including
DHEA, DHEA-S, and pregnenolone, are involved in the pathophysiology of
schizophrenia in male patients, but not in female ones. Therefore, our findings
suggest that neurosteroids may be associated with gender differences in
susceptibility to schizophrenia.
PMID- 28686905
TI - Anxiety in the context of cancer: A systematic review and development of an
integrated model.
AB - Anxiety is common in the context of cancer, but there are few theoretical models
that apply to people with cancer across the trajectory of their illness. The aims
of this review are to identify existing theories and to propose an integrated
model of cancer-related anxiety. Using a systematic literature search of Medline,
Premedline and PsycINFO databases, we identified nine theoretical models of
anxiety in the context of cancer. We reviewed these for psychological concepts
that fell under five themes: pre-existing schema, the inherent nature of cancer,
cognitive factors, coping responses and contextual factors. From these themes, we
integrated concepts from different models to develop a theoretical framework to
explain the development and maintenance of anxiety in the context of cancer. The
resulting model suggests that pre-existing schema, past experiences of cancer, an
intolerance of uncertainty and meta-cognitive beliefs about worry interact with
the inherent nature of cancer to produce overwhelming distress. The distress
activates cognitive processes characterized by vigilance, worry and rumination.
Attempts to cope by re-establishing control, and a pattern of vigilance to cancer
related cues and/or avoidance reinforce anxiety, in the context of a range of
systemic factors that can either buffer against or worsen the anxiety.
PMID- 28686906
TI - Lamotrigine serum levels: Ceiling effect in people with epilepsy in remission?
AB - BACKGROUND: Antiepileptic drug titration in epilepsy remains mostly empirical.
Since in practice seizure remission may be obtained with low doses, we aimed to
determine whether patients in remission have lower lamotrigine levels than those
with ongoing seizures. METHODS: Retrospective comparison of the distribution of
lamotrigine levels among unselected patients in remission and with ongoing
seizures. Remission was defined as 3 times the longuest interseizure interval and
at least one year. Only trough levels were analyzed. RESULTS: Between 2009 and
2014, we identified 93 adults, among whom 10 were in remission. Patients in
remission had significantly (p=0.008) lower serum levels (median 2.3mg/L, range:
0.7-8.2) than those with ongoing seizures (median 5.4mg/L, range: 1.1-18.2). We
did not find any patient in remission with levels higher than 8.2mg/L.
Distribution of dosages also differed among the groups, but less significantly
(median: 175 vs 300mg, p=0.03). CONCLUSION: An association between lamotrigine
serum levels and seizure response can be observed. This suggests the existence of
a ceiling level, above which remission is unlikely and should prompt
antiepileptic medication switch rather than further up-titration of lamotrigine
in drug-naive patients with epilepsy.
PMID- 28686907
TI - Factors affecting quality of life in Hungarian adults with epilepsy: A comparison
of four psychiatric instruments.
AB - PURPOSE: We investigated the impact of 19 factors on life quality in Hungarian
patients with epilepsy. Wellbeing was evaluated by several inventories to
investigate the impact of factors in more detail. METHODS: A cross-sectional
study was performed in 170 patients. Wellbeing was evaluated with the WHO-5 Well
being Index (WHOQOL-5), Diener Satisfaction with Life Scale (SwLS), and the
Quality of Life in Epilepsy-31 Questionnaire (Qolie-31). We investigated their
association with demographic characteristics, general health status, epilepsy,
and its treatment. The impact of these factors on illness perception (Illness
Perception Questionnaire, IPQ) was also studied. RESULTS: The four measures
correlated highly significantly. In addition, the predictive power of factors was
comparable with the four inventories as evaluated by Multiple Regression. Factors
explained 52%, 41%, 63% and 46% in the variance of WHOQOL-5, SwLS, Qolie-31, and
IPQ scores, respectively. However, associations with particular factors were
instrument-specific. The WHOQOL-5 was associated with factors indicative of
general health. SwLS scores were associated with health-related and several
demographic factors. Neither showed associations with epilepsy-related factors.
All four categories of factors were associated with Qolie-31 and IPQ scores.
Factors had an additive impact on IPQ, but not on Qolie-31. SIGNIFICANCE: Our
findings reveal interactions between the method of life quality assessment and
the factors that are identified as influencing life quality. This appears to be
the first study that analyses the factors that influence illness perception in
epilepsy patients, and suggests that the IPQ may become a valuable tool in
epilepsy research.
PMID- 28686908
TI - A longitudinal study investigating neural processing of speech envelope
modulation rates in children with (a family risk for) dyslexia.
AB - Recent evidence suggests that a fundamental deficit in the synchronization of
neural oscillations to temporal information in speech may underlie phonological
processing problems in dyslexia. Since previous studies were performed cross
sectionally in school-aged children or adults, developmental aspects of neural
auditory processing in relation to reading acquisition and dyslexia remain to be
investigated. The present longitudinal study followed 68 children during
development from pre-reader (5 years old) to beginning reader (7 years old) and
more advanced reader (9 years old). Thirty-six children had a family risk for
dyslexia and 14 children eventually developed dyslexia. EEG recordings of
auditory steady-state responses to 4 and 20 Hz modulations, corresponding to
syllable and phoneme rates, were collected at each point in time. Our results
demonstrate an increase in neural synchronization to phoneme-rate modulations
around the onset of reading acquisition. This effect was negatively correlated
with later reading and phonological skills, indicating that children who exhibit
the largest increase in neural synchronization to phoneme rates, develop the
poorest reading and phonological skills. Accordingly, neural synchronization to
phoneme-rate modulations was found to be significantly higher in beginning and
more advanced readers with dyslexia. We found no developmental effects regarding
neural synchronization to syllable rates, nor any effects of a family risk for
dyslexia. Altogether, our findings suggest that the onset of reading instruction
coincides with an increase in neural responsiveness to phoneme-rate modulations,
and that the extent of this increase is related to (the outcome of) reading
development. Hereby, dyslexic children persistently demonstrate atypically high
neural synchronization to phoneme rates from the beginning of reading acquisition
onwards.
PMID- 28686909
TI - Unraveling the role of maternal anti-HLA class I antibodies in fetal and neonatal
thrombocytopenia-Antibody specificity analysis using epitope data.
AB - Anti-HLA class I antibodies have been suggested as a possible cause of fetal and
neonatal alloimmune thrombocytopenia (FNAIT). The aim of this study was to
characterize maternal anti-HLA class I alloantibodies in suspected cases of
FNAIT. The study population consisted of all nationwide referrals of neonates
with suspected FNAIT to the National Unit for Platelet Immunology in Tromso,
Norway, during 1998-2009 (cases), and 250 unselected pregnancies originally
included in a prospective study (controls). Inclusion criterion was a positive
screening for maternal anti-HLA class I antibodies. Neonates with other
identifiable causes of thrombocytopenia, including maternal anti-human platelet
antigens (HPA) antibodies, were excluded. Ultimately, 50 cases with suspected
FNAIT were compared with 60 controls. The median neonatal platelet count nadir
among cases was 24*109/L (range 4-98*109/L). Five children (10%) were reported to
have intracranial hemorrhage. Maternal and neonatal HLA class I genotype was
available for 33 mother/child pairs (66%). Immunization was not tied to any
particular HLA class I antigen. Using epitope mapping, we could demonstrate that
the maternal anti-HLA class I antibodies were specific towards mismatched
paternally-inherited fetal epitopes, with little reactivity towards any third
party epitopes. Antibody reactivity patterns were similar to those found among
controls, although the mean fluorescence intensities (MFI) among cases were
significantly higher. This study demonstrates the value of using data on HLA
epitope expression, instead of HLA antigens, to examine alloimmune responses in
connection with neonatal thrombocytopenia. Our findings support the idea that
maternal anti-HLA class I antibodies are involved in FNAIT.
PMID- 28686910
TI - Polar transport in plants mediated by membrane transporters: focus on mechanisms
of polar auxin transport.
AB - Directional cell-to-cell transport of functional molecules, called polar
transport, enables plants to sense and respond to developmental and environmental
signals. Transporters that localize to plasma membranes (PMs) in a polar manner
are key components of these systems. PIN-FORMED (PIN) auxin efflux carriers,
which are the most studied polar-localized PM proteins, are implicated in the
polar transport of auxin that in turn regulates plant development and tropic
growth. In this review, the regulatory mechanisms underlying polar localization
of PINs, control of auxin efflux activity, and PIN abundance at PMs are
considered. Up to date information on polar-localized nutrient transporters that
regulate directional nutrient movement from soil into the root vasculature is
also discussed.
PMID- 28686911
TI - Synthesis and evaluation of N-heteroaromatic ring-based analogs of piperlongumine
as potent anticancer agents.
AB - Piperlongumine (PL) selectively targets a wide spectrum of cancer cells and
induces their death by triggering various pathways, including apoptosis, necrosis
and autophagy. However, the poor solubility is a serious concern for intensive
study and clinical application. We synthesized its analogs 1-9 by replacement of
the trimethoxyphenyl of PL with an N-heteroaromatic ring and/or not introduction
of 2-Cl. These compounds improved aqueous solubility and displayed potent
anticancer activity. The most active compound 9 selectively enhanced ROS levels
in colon cancer cells and inhibited the cell proliferation but sparing non-tumor
colon cells. Importantly, 9 significantly repressed tumor growth in an HCT-116
xenograft mouse model, suggesting that these N-heteroaromatic ring-based analogs
of PL warrant further investigation.
PMID- 28686912
TI - Antiproliferative and apoptotic activities of sequence-specific histone
acetyltransferase inhibitors.
AB - In parallel to monomeric epigenetic regulators, sequence-specific epigenetic
regulators represent versatile synthetic dual-target ligands that achieve
regulatory control over multi-gene networks. Development of DNA-binding domain
(DBD)-HDAC inhibitors and DBD-HAT activators, which result in increased histone
acetylation, has become one promising research field. However, there is no report
regarding the gene regulatory pattern by sequence-specific epigenetic repressor.
We report here for the first time, the synthesis of DBD-HAT inhibitors and
demonstrate that these conjugates could retain their dual-target activity using
predicted working model of thermal stability assay and in vitro HAT activity
assay. Evaluation of antiproliferative activity in cancer cells showed that 2
(with a medium linker length of 13-atom) exhibited the highest antiproliferative
activity in p53 wild-type cancer cell lines (IC50 of 1.8-2.6 MUM in A549 and MV4
11 cells) and not in p53 mutant cancer cell lines. A mechanistic investigation
using microarray analysis and an apoptotic assay showed that the
antiproliferative effect of 2 occurred via the up-regulation of p53 target genes,
and the subsequent initiation of p53-dependent apoptosis. Our research on
sequence-specific dual-target epigenetic repressor offers us an alternative way
to modulate HAT-governed therapeutically important genes and contributes to offer
a fresh insight into antitumor therapeutics.
PMID- 28686914
TI - An optimized dRVVT-based assay to estimate the intensity of anticoagulation in
patients treated with direct oral anticoagulants.
AB - BACKGROUND: The dilute Russell's viper venom time (dRVVT) has been suggested for
the assessment of the intensity of anticoagulation of all direct oral
anticoagulants (DOACs). This study aimed to compare the performance of an
optimized liquid-stable dRVVT-based DOAC assay (DRVV-DOAC) on clinical samples
before and after mixing these with normal pooled plasma (NPP). METHODS: Forty-one
apixaban, 25 dabigatran, 56 rivaroxaban and 49 vitamin K antagonists (VKAs)
plasma samples were included for retrospective analysis. Plasma DOAC
concentrations were determined by liquid chromatography coupled with tandem mass
spectrometry. INR was determined for all VKA samples. DRVV-DOAC was performed
with an original ready-to-use reagent (Haematex ResearchTM) where plasma samples
were tested neat and in a 1:1 mix with NPP. RESULTS: Plasma concentrations ranged
from 1 to 406ng/ml for apixaban, 0 to 386ng/ml for dabigatran and 0 to 719ng/ml
for rivaroxaban. INR ranged from 2.2 to 6.1. DRVV-DOAC correlated well with
plasma concentrations (r2=0.70, 0.94, 0.63 (non-mixed procedure) and 0.77, 0.97,
0.86 (mixed procedure) for apixaban, dabigatran and rivaroxaban, respectively).
DRVV-DOAC measurements in the normal range ruled out dabigatran and rivaroxaban
concentrations above 30 and 50ng/ml, but performance was lower for apixaban. DRVV
DOAC was sensitive to VKA samples but poorly reflected INR values. When VKA
samples were mixed with NPP, DRVV-DOAC measurements decreased to values close to
baseline clotting time. CONCLUSIONS: DRVV-DOAC is a quick method which showed
increased sensitivity compared with other phospholipid-rich dRVVT reagents
already investigated. Mixing samples with NPP improved the specificity but
reduced sensitivity, especially for apixaban.
PMID- 28686913
TI - Guidance for the diagnosis of pulmonary embolism during pregnancy: Consensus and
controversies.
AB - Pulmonary embolism (PE) is one of the leading causes of maternal mortality
despite a low incidence of PE during pregnancy. Several challenges surround the
diagnosis of PE in pregnant women and the existing clinical guidelines provide
weak recommendations on selecting the appropriate investigations for suspected PE
in pregnancy. The purpose of this narrative review is to compare and contrast the
recommendations of current clinical guidelines and review the evidence
underpinning the recommendations on the evaluation of suspected PE in pregnancy.
Consensus and controversies, knowledge gaps and areas requiring further research
will be highlighted.
PMID- 28686915
TI - Fluorescence turn-off-on probe based on polypyrrole/graphene quantum composites
for selective and sensitive detection of paracetamol and ascorbic acid.
AB - In this work, we presented a novel biosensor for rapid detection of paracetamol
and ascorbic acid. The novel biosensor was based on the fluorescent "turn off-on"
of polypyrrole/graphene quantum dots (PPy/GQDs) composites. The composites
exhibit strong fluorescence emission, which is dramatically enhanced as high as
three times than that of pure GQDs. It is found that the fluorescence intensity
of PPy/GQDs can be efficiently quenched by N-acetyl-p-benzoquinone (4-AOBQ), the
oxidation product of paracetamol (PAR). And a turn-on fluorescence signal was
observed when 4-AOBQ is reduced by ascorbic acid (AA). The quenched and recovered
fluorescence intensity of PPy-GQDs was proportional to the concentration of PAR
(0.067-233MUg/L) and AA (3.33-997.5MUg/L) respectively. The limit of detection is
0.022MUg/L for PAR and 1.05MUg/L for AA. The present method was applied to the
determination of PAR and AA in human serum samples with satisfactory results.
PMID- 28686916
TI - Inclusion study of hourglass amethyst from Boudi (Morocco) by Raman
microspectroscopy and microthermometric measurements.
PMID- 28686917
TI - Theoretical study of excited-state proton transfer of 2,7-diazaindole.(H2O)2
cluster via hydrogen bonding dynamics.
AB - A new chromophore, 2,7-diazaindole (2,7-DAI), has been designed to surpass the
limitation of 7-azaindole (7AI). It exhibits remarkable water catalyzed proton
transfer properties. Excited-state proton transfer (ESPT) has been investigated
based on the time-dependent density functional theory method. The calculated
vertical excitation energies in the S0 and S1 states agree well with the
experimental values. Proton transfer couples with hydrogen-bonding dynamics
between the 2,7-diazaindole and the surrounding water molecules. Hydrogen bond
strengthening has been testified in the S1 state based on a comparison of primary
bond lengths and hydrogen bond energy that is involved in the intermolecular
hydrogen bond between the S0 and S1 states. Frontier molecular further suggest
that the electron density changes between the ground and excited states serve as
basic driving forces for proton transfer. We determined the potential-energy
curves of the S0 and S1 states to characterize the ESPT process. This work
explains that the ESPT process for 2,7-DAI.(H2O)2 clusters at the molecular
level, and highlights the importance of hydrogen bonding in ESPT.
PMID- 28686918
TI - Synthesis, crystal structure, fluorescence properties of 1D chain Manganese (II)
and Cadmium (II) complexes.
AB - Two complexes, {[Mn(3-pmpmd)2(Cl)2].2H2O}n(1), {[Cd(3-pmpmd)
(I)2].CHCl3.H2O}n(2), (3-pmpmd, N,N'-bis(3-pyridylmethyl)pyromellitic diimide)
were synthesized and characterized by elemental analyses, IR spectroscopy,
thermogravimetric analyses, and X-ray single-crystal structure analysis. The
conformations of 3-pmpmd ligand affect their structural diversity. Complex 1 is a
1D double chain structure in edge-to-edge arrangement by pi?pi interactions.
Complex 2 is a typical 1D zigzag chain structure arranged in a parallel array
containing 1D channel to accommodate the chloroform and water guest molecules.
Thermal stabilities and fluorescence properties of both complexes were
investigated. The solution of complex 2 in DMF can sense for I- anion by
quenching fluorescence intensity, whereas other anions increasing fluorescence
intensity.
PMID- 28686919
TI - A simple and low cost dual-wavelength beta-correction spectrophotometric
determination and speciation of mercury(II) in water using chromogenic reagent 4
(2-thiazolylazo) resorcinol.
AB - The most common problems in spectrophotometric determination of various complex
species originate from the background spectral interference. Thus, the present
study aimed to overcome the spectral matrix interference for the precise analysis
and speciation of mercury(II) in water by dual-wavelength beta-correction
spectrophotometry using 4-(2-thiazolylazo) resorcinol (TAR) as chromogenic
reagent. The principle was based on measuring the correct absorbance for the
formed complex of mercury(II) ions with TAR reagent at 547nm (lambda max). Under
optimized conditions, a linear dynamic range of 0.1-2.0MUgmL-1 with correlation
coefficient (R2) of 0.997 were obtained with lower limits of detection (LOD) of
0.024MUgmL-1 and limit of quantification (LOQ) of 0.081MUgmL-1. The values of RSD
and relative error (RE) obtained for beta-correction method and single wavelength
spectrophotometry were 1.3, 1.32% and 4.7, 5.9%, respectively. The method was
validated in tap and sea water in terms of the data obtained from inductively
coupled plasma-optical emission spectrometry (ICP-OES) using student's t and F
tests. The developed methodology satisfactorily overcomes the spectral
interference in trace determination and speciation of mercury(II) ions in water.
PMID- 28686920
TI - Waterberg coal characteristics and SO2 minimum emissions standards in South
African power plants.
AB - Key characteristics of coal samples from the supply stock to the newly
commissioned South African National Power Utility's (Eskom's) Medupi Power
Station - which receives its supply coal from the Waterberg coalfield in
Lephalale (Limpopo Province, South Africa) - were evaluated. Conventional coal
characterisation such as proximate and ultimate analysis as well as determination
of sulphur forms in coal samples were carried out following the ASTM and ISO
standards. Coal was classified as medium sulphur coal when the sulphur content
was detected in the range 1.15-1.49 wt.% with pyritic sulphur (>=0.51 wt.%) and
organic sulphur (>=0.49 wt.%) accounted for the bulk of the total sulphur in
coal. Maceral analyses of coal showed that vitrinite was the dominant maceral (up
to 51.8 vol.%), whereas inertinite, liptinite, reactive semifusinite and visible
minerals occurred in proportions of 22.6 vol.%, 2.9 vol.%, 5.3 vol.% and 17.5
vol.%, respectively. Theoretical calculations were developed and used to predict
the resultant SO2 emissions from the combustion of the Waterberg coal in a
typical power plant. The sulphur content requirements to comply with the minimum
emissions standards of 3500 mg/Nm3 and 500 mg/Nm3 were found to be <=1.37 wt.%
and <=0.20 wt.%, respectively.
PMID- 28686921
TI - E-waste Management and Refurbishment Prediction (EMARP) Model for Refurbishment
Industries.
AB - This paper proposes a novel algorithm for establishing a standard methodology to
manage and refurbish e-waste called E-waste Management And Refurbishment
Prediction (EMARP), which can be adapted by refurbishing industries in order to
improve their performance. Waste management, particularly, e-waste management is
a serious issue nowadays. Computerization has been into waste management in
different ways. Much of the computerization has happened in planning the waste
collection, recycling and disposal process and also managing documents and
reports related to waste management. This paper proposes a computerized model to
make predictions for e-waste refurbishment. All possibilities for reusing the
common components among the collected e-waste samples are predicted, thus
minimizing the wastage. Simulation of the model has been done to analyse the
accuracy in the predictions made by the system. The model can be scaled to
accommodate the real-world scenario.
PMID- 28686922
TI - Sulfate sorption on rape (Brassica campestris L.) straw biochar, loess soil and a
biochar-soil mixture.
AB - The effects of biochar amendment on sulfur behavior in soils are unknown. In this
paper, sulfate (SO42-) sorption on rape (Brassica campestris L.) straw biochar
produced at 600 degrees C (BC), loess soil (soil) and a 1:9 (w/w) biochar-soil
mixture (BC-soil) was investigated by batch experiments. The effects of contact
time, initial SO42- concentration, temperature and solution pH value on sorption
were tested. Kinetics, isotherms and thermodynamics for sorption were
investigated. Pre- and post-sorption characterizations of BC and soil were
respectively studied using Fourier transform infrared (FTIR) and X-ray
diffraction (XRD) spectroscopy, respectively. It has been shown that SO42-
sorption on three sorbents was well described by pseudo-second-order kinetic
model. The sorption isotherms could be fitted using Langmuir and Freundlich
models. BC amendment did not increase the sorption capacity of soil for SO42-.
The values of DeltaG0, DeltaH0 and DeltaS0 indicated that the nature of sorption
was spontaneous, endothermic and feasible. Increasing solution pH value led to a
slight reduction in the sorption amount of SO42-. Sulfate was mainly sorbed onto
BC through electrostatic interaction, whereas onto the soil via electrostatic
interaction and formation of poorly soluble CaSO4.
PMID- 28686923
TI - Rare case of incarcerated obturator hernia: Case report and review of literature.
AB - INTRODUCTION: Obturator hernia is a rare condition accounting for less than 1% of
all intra abdominal hernias. Clinical diagnosis is considered a challenge for
most surgeons. It usually appears as an intestinal obstruction. Confirmation of
diagnosis is carried out by means of imaging or during surgery. CASE REPORT: An
85-year-old female patient, with symptoms of intestinal obstruction of 24h
duration was admitted to the emergency room of Unimed Hospital - Belo Horizonte.
Abdominal computed tomography (CT) demonstrated a herniation of the small bowel
through the right obturator canal with an intestinal distension proximally. At
laparotomy, the presence of a right obturator hernia with an ileal strangulation
was confirmed. Segmental enterectomy with primary anastomosis and herniorrhaphy
for the closure of the obturator foramen were performed. DISCUSSION: Obturator
hernias typically affect women, elderly, emaciated and multiparous. Symptoms are
non-specific and associated with an intestinal obstruction. Howship-Romberg sign,
considered pathognomonic, is generally absent. Abdominal CT scan can aid in pre
operative diagnosis and the treatment is surgical. CONCLUSION: Early diagnosis
and surgical treatment are imperative in obturator hernias due to the high
morbidity and mortality that occur in cases where the intervention is delayed.
PMID- 28686924
TI - Emergency splenectomy for trauma in the setting of splenomegaly, axillary
lymphadenopathy, and incidental B-cell chronic lymphocytic leukemia: A case
report.
AB - INTRODUCTION: The spleen is the most commonly injured intra-abdominal solid organ
following blunt trauma. B-cell chronic lymphocytic leukemia (CLL) is the most
common leukocytic dyscrasia affecting adults in Western countries. Splenomegaly
with axillary and retroperitoneal lymphadenopathy are common physical findings.
This case investigates an emergency splenectomy in a community hospital involving
a 45-year-old man with blunt abdominal trauma following an assault with
incidental splenomegaly and axillary lymphadenopathy, with surgical pathology
findings of B-cell CLL. PRESENTATION OF CASE: A 45- year-old man without past
medical or family history who was the victim of an assault presented to the
emergency department 6h later with left upper quadrant pain and radiation to the
left flank and a positive Kehr sign. An elevated absolute lymphocyte count above
7*109 and CT confirmation of a Grade V splenic laceration with splenomegaly,
axillary lymphadenopathy, with hemodynamic compromise led to an exploratory
laparotomy and emergency splenectomy regardless of the potential for malignancy.
DISCUSSION: Hemoperitoneum with blunt splenic injury (BSI) caused by abdominal
trauma with hemodynamic instability should be treated with exploratory laparotomy
and splenectomy even in the face of potential malignancy with splenomegaly and
axillary lymphadenopathy. An appropriate oncologic work up and treatment can be
provided after the emergency intervention. CONCLUSION: An emergency splenectomy
is an appropriate operative intervention for a grade V splenic laceration with
hemoperitoneum, splenomegaly, and axillary lymphadenopathy regardless of the
potential for a neoplastic process such as B-cell CLL. Post-splenectomy
vaccinations and oncologic follow-up for systemic chemotherapy should be
facilitated after recovery.
PMID- 28686925
TI - Recurrent gastric cancer metastasizing to the bone marrow: A case report of a
rare presentation.
AB - INTRODUCTION: Gastric cancer notoriously recurs post curative surgical resection.
While there may be visceral metastasis to peritoneal surfaces, bone marrow
involvement may also occur although with rarity. We present a case report of
recurrent gastric cancer with bone marrow metastasis in a patient with no
evidence of systemic disease on follow-up for two years post surgical resection.
This case demonstrates the need of heightened clinical suspicion in these
patients. METHODS: We reviewed the medical records of a patient who presented
with metastatic gastric adenocarcinoma to the bone marrow two years post R0
subtotal gastrectomy with Roux-en-Y gastrojejunostomy without evidence of
systemic disease on follow up for two years. RESULTS: Laboratory and imaging
studies of the patient on presentation two years post R0 subtotal gastrectomy
with Roux-en-Y gastrojejunostomy is as follows; elevated alkaline phosphatase
(ALP) of 472 U/L, CT chest/abdomen/pelvis that showed multiple new sclerotic
lesions throughout osseous structures suspicious for metastasis, PET/CT that
showed many sclerotic lesions throughout the axial and appendicular skeleton,
some FDG-avid and suspicious for active osseous metastasis. Bone marrow biopsy
showed metastatic poorly differentiated carcinoma consisted with known history of
gastric cancer. CONCLUSION: Gastric cancer has a high rate of recurrence post
curative surgery. Despite the rarity of bone marrow metastasis, a high level of
suspicion should be maintained in patients presenting with elevated ALP and
evidence of pancytopenia post curative surgery.
PMID- 28686926
TI - Asian-Canadian children and families involved in the child welfare system in
Canada: A mixed methods study.
AB - OBJECTIVE: The purpose of the study is to understand the similarities and
differences in child welfare involvement for Asian- Canadian (East and Southeast
Asian) versus White-Canadian children and families involved in the child welfare
system in Canada, and to consider the implications and recommendations for
service. This mixed methods study began by replicating this author's previous
study that found significant differences in the case characteristics and services
used by Asian compared to non-Asian families in the child welfare system. The
present study used a mixed method approach to further build a comprehensive
descriptive understanding of Asian-Canadian children and families involved in the
child welfare system at national and local levels. METHODS: Secondary data
analysis of the 2008 Canadian Incidence Study of Reported Child Abuse and Neglect
(CIS-2008) was conducted to identify the case characteristics (such as referral
source, investigation type, and primary maltreatment type) and short-term service
outcome (such as substantiation decision and decision to transfer to ongoing
child protection services) of child maltreatment investigations involving Asian
Canadian children and families in the child welfare system. The results were
presented to focus group participants in a workshop, and a semi-structured
interview guide was used to document child welfare workers' experience with and
perception of Asian-Canadian service users. RESULTS: The results indicated
substantial differences between Asian- Canadian and White-Canadian children and
families investigated by child welfare agencies in respect to the household
composition, maltreatment type, substantiation decision and decision to transfer
to ongoing child protection services. Child welfare workers validated the results
from secondary data analysis of the CIS-2008 and offer a broader cultural and
structural context for understanding child welfare involvement with Asian
Canadians. CONCLUSION: Asian-Canadian children and families bring a diversity of
cultural values and family norms. This study prompts further consideration for
social work practice and policies in working with Asian-Canadian children and
families involved in the child welfare system.
PMID- 28686927
TI - Servo controlled versus manual cooling methods in neonates with hypoxic ischemic
encephalopathy.
AB - BACKGROUND: Therapeutic hypothermia is known to improve outcomes in neonates with
hypoxic ischemic encephalopathy (HIE). There are no studies that have compared
servo controlled cooling (SCC) versus manually controlled cooling (MCC) methods
in HIE. AIM: To compare the outcomes of SCC versus MCC in neonates with HIE.
METHODS AND OUTCOME MEASURES: Between Jan 2008 and May 2011, MCC with cool-gel
packs was used to achieve rectal temperatures of 33.5 to 34.5 degrees C in our
units. Subsequently, we changed to SCC to achieve rectal temperatures of 33 to 34
degrees C. 105 neonates received SCC whereas 95 received MCC. Retrospective study
with multivariate analysis was conducted comparing thermoregulation (primary
outcome) and neurodevelopmental outcomes of SCC versus MCC. RESULTS: In the SCC
group, 72.3% had stage 2 or 3 HIE versus 77.9% in the MCC. The remaining had
stage 1, but attending neonatologists decided to provide cooling. Prescribed
rectal temperatures were achieved in 80.5% (5768/7168) instances in SCC versus
72.9% (4449/6108) in MCC (p<0.0001). There were no significant differences in the
incidence of 'death or moderate-severe disability' [SCC 26/85 vs MCC 26/87,
adjusted odds ratio: 1.29, 95% CI: 0.48, 3.42; p=0.614]. The results were similar
after excluding stage 1 HIE [SCC 25/66 vs MCC 26/69, adjusted odds ratio: 1.01,
95% CI: 0.50, 2.02; p=0.981]. CONCLUSIONS: SCC resulted in better
thermoregulation in neonates undergoing therapeutic hypothermia. There were no
significant differences in neurodevelopmental outcomes, but the study was
underpowered to answer this. Randomized trials are needed to fine-tune various
aspects of TH in neonates with HIE.
PMID- 28686928
TI - Surface characteristics and potential ecological risk evaluation of heavy metals
in the bio-char produced by co-pyrolysis from municipal sewage sludge and
hazelnut shell with zinc chloride.
AB - Municipal sewage sludge (MSS) and hazelnut shell were used for co-pyrolysis by
chemical activation with ZnCl2. The surface characteristics and potential
ecological risk evaluation of heavy metals in the bio-char produced by co
pyrolysis were analyzed by surface analyzer and BCR sequential extraction. When
raw materials with ZnCl2 (3mol/L) were co-pyrolyzed at 500 degrees C for 90min,
specific surface area of the bio-char is 598.73m2/g, and iodine absorption number
is 607.85mg/g. For microcosmic surface of the bio-char, the ratio of micropore
area is stabilized from 0.74 to 0.80 of the total specific surface area, and
hazelnut shell is effective to generate microporous construction. For the
migration and transformation behavior of heavy metals, pyrolysis promoted mobile
fraction (F1 and F2) to stable fraction (F3 and F4) with increasing pyrolysis
temperature. The potential ecological risk of heavy metals transforms from
considerable risk to low risk after pyrolysis at 500 degrees C.
PMID- 28686929
TI - Polyol production from waste materials by genetically modified Yarrowia
lipolytica.
AB - Sugar alcohols (polyols) are sweeteners with many industrial applications. In
this study, a fermentation process of polyol production based on waste substrates
- raw industrial molasses and crude glycerol - was tested. The yeast strain
Yarrowia lipolytica Wratislavia K1 was genetically modified by overexpression of
the Saccharomyces cerevisiae SUC2 gene and overexpression of the native GUT1
gene. This process allowed for sucrose utilization and rapid glycerol
assimilation by the engineered strain. In this study, the obtained strain AIB pAD
UTGut1 produced 100.65+/-3.75g/l of polyols, with productivity of 1.09+/-0.9g/lh
and yield of 0.67+/-0.2g/g. This is the first study describing efficient polyol
production by the modified Y. lipolytica strain from industrial raw molasses and
crude glycerol. By process optimization, we established conditions for abundant
polyol synthesis from low-value substrates.
PMID- 28686930
TI - Characterization of the O-antigen polysaccharide derived from Pantoea agglomerans
IG1 lipopolysaccharide.
AB - A polysaccharide fraction was isolated from the Pantoea agglomerans IG1
lipopolysaccharide (IP-PA1), and its O-antigenic polysaccharide was characterized
by chemical analyses and 1D and 2D 1H and 13C NMR spectroscopy. The
polysaccharide is composed of linear tetrasaccharide repeating units, consisting
of glucose and rhamnose, where 40% of one of the rhamnose residues is substituted
with glucose: ->2)-alpha-l-Rhap-(1->6)-alpha-d-Glcp-(1->2)-[beta-d-Glcp-(1
>3)]0.4-alpha-l-Rhap-(1->2)-alpha-l-Rhap-(1->.
PMID- 28686931
TI - Sulfate enhances the dissimilatory arsenate-respiring prokaryotes-mediated
mobilization, reduction and release of insoluble arsenic and iron from the
arsenic-rich sediments into groundwater.
AB - Dissimilatory arsenate-respiring prokaryotes (DARPs) play key roles in the
mobilization and release of arsenic from mineral phase into groundwater; however,
little is known about how environmental factors influence these processes. This
study aimed to explore the effects of sulfate on the dissolution and release of
insoluble arsenic. We collected high-arsenic sediment samples from different
depths in Jianghan Plain. Microcosm assays indicated that the microbial
communities from the samples significantly catalyzed the dissolution, reduction
and release of arsenic and iron from the sediments. Remarkably, when sulfate was
added into the microcosms, the microorganisms-mediated release of arsenic and
iron was significantly increased. To further explore the mechanism of this
finding, we isolated a novel DARP, Citrobacter sp. JH001, from the samples.
Arsenic release assays showed that JH001 can catalyze the dissolution, reduction
and release of arsenic and iron from the sediments, and the presence of sulfate
in the microcosms also caused a significant increase in the JH001-mediated
dissolution and release of arsenic and iron. Quantitative PCR analysis for the
functional gene abundances showed that sulfate significantly increased the
arsenate-respiring reductase gene abundances in the microcosms. Thus, it can be
concluded that sulfate significantly enhances the arsenate-respiring bacteria
mediated arsenic contamination in groundwater.
PMID- 28686932
TI - Preparation of novel magnetic molecular imprinted polymers nanospheres via
reversible addition - fragmentation chain transfer polymerization for selective
and efficient determination of tetrabromobisphenol A.
AB - A well-defined molecularly imprinted polymer nanospheres with excellent specific
recognition ability was prepared on Fe3O4 nanoparticles via the combination of
click chemistry and surface-initiated reversible addition-fragmentation chain
transfer (RAFT) polymerization and using Tetrabromobisphenol A as template.
Concretely, Fe3O4 nanoparticles were prepared by solvothermal method and then
modified by 4-vinylbenylchloride through distillation-precipitation, which makes
azide groups easily introduced on the surface of magnetic nanoparticles to form
the relatively large amount of benzyl chloride groups. With high efficiency,
alkyne terminated RAFT chain transfer agent were then immobilized onto the
surface of Fe3O4 by means of click chemistry, which is Cu(I)-catalyzed azide
alkyne cycloaddition (CuAAC). The highly uniform imprinted thin film was finally
fabricated on the surface of RAFT agent modified Fe3O4 nanoparticles. The binding
results demonstrated that as-prepared imprinted beads exhibited remarkable
molecular imprinting effects to the template molecule, fast rebinding kinetics
and an excellent selectivity to compounds with similar configuration.
PMID- 28686933
TI - Personal resources and depression in schizophrenia: The role of self-esteem,
resilience and internalized stigma.
AB - Depression in schizophrenia represents a challenge from a diagnostic,
psychopathological and therapeutic perspective. The objective of this study is to
test the hypothesis that resilience and self-stigma affect depression severity
and to evaluate the strength of their relations in 921 patients with
schizophrenia. A structural equation model was tested where depression is
hypothesized as affected by resilience, internalized stigma, gender and negative
symptoms, with the latter two variables used as exogenous covariates and the
former two as mediators. The analysis reveals that low resilience, high negative
symptoms, female gender were directly associated with depression severity, and
internalized stigma acted only as a mediator between avolition and resilience,
with similar magnitude. The cross-sectional study design and the variable
selection limit the generalizability of the study results. The model supports a
complex interaction between personal resources and negative symptoms in
predicting depression in schizophrenia. The clinical implication of these
findings is that personal resources could be a significant target of psychosocial
treatments.
PMID- 28686934
TI - Z-drug for schizophrenia: A systematic review and meta-analysis.
AB - No systematic reviews and meta-analyses on the use of Z-drug for schizophrenia
are available. Randomized, placebo-controlled, or non-pharmacological
intervention-controlled trials published before 03/20/2017 were retrieved from
major healthcare databases and clinical trial registries. A meta-analysis
including only randomized, placebo-controlled trials was performed. Efficacy
outcomes were measured as improvement in overall schizophrenia symptoms, total
sleep time, and wake after sleep onset. Safety/acceptability outcomes were
discontinuation rate and individual adverse events. Four trials [1 alpidem
placebo-controlled study (n=66), 2 eszopiclone placebo-controlled studies (n=60),
and 1 eszopiclone, shallow needling-controlled study (n=96)] were identified. The
meta-analysis showed no significant differences in any outcome between pooled Z
drug and placebo treatment groups. For individual studies, alpidem was superior
to placebo in improving the overall schizophrenia symptoms. One of the
eszopiclone studies showed that eszopiclone was superior to placebo in improving
the Insomnia Severity Index scores. Another eszopiclone study showed that
eszopiclone did not differ from shallow needling therapy in improving both
schizophrenia- and insomnia-related symptoms. Although this study failed to show
significant benefits for the use of Z-drug in the treatment of schizophrenia, it
showed that short-term use of eszopiclone is an acceptable method for treating
persistent insomnia among these patients.
PMID- 28686935
TI - Effectiveness of an individually-tailored computerised CBT programme (Deprexis)
for depression: A meta-analysis.
AB - Computerised cognitive behavioural therapy (cCBT) programmes differ widely but
have rarely been evaluated separately through meta-analysis. Through a meta
analysis of randomised controlled trials, we investigated the effectiveness of
'Deprexis', an unconventional and individually-tailored cCBT programme for
depression. Comparisons from eight studies (N = 2402) demonstrated the
effectiveness of Deprexis for depressive symptoms at post-intervention, with a
medium effect size (g = 0.54, 95% CI: 0.39-0.69). Analogous results arose when
study quality, screening, and randomisation procedure were taken into account.
The level of guidance provided alongside Deprexis had a statistically non
significant impact upon the effect size. There was no significant difference in
the performance of Deprexis in developer-led trials compared with non-developer
trials, and no publication bias was detected. The weighted-average dropout rate
for participants allocated to Deprexis treatment arms in included studies was
26.5%. Based primarily on trials in naturalistic community settings, the findings
support the effectiveness of Deprexis for depressive symptoms. The positive
findings add to the growing evidence-base for individually-tailored cCBT
programmes and point to the need for further investigations of apparent
systematic differences in the effectiveness of specific cCBT programmes.
PMID- 28686936
TI - Differentiation of low- and high-grade clear cell renal cell carcinoma: Tumor
size versus CT perfusion parameters.
AB - PURPOSE: To compare the utility of tumor size and CT perfusion parameters for
differentiation of low- and high-grade clear cell renal cell carcinoma (RCC).
MATERIALS AND METHODS: Tumor size, Equivalent blood volume (Equiv BV),
permeability surface-area product (PS), blood flow (BF), and Fuhrman pathological
grading of clear cell RCC were retrospectively analyzed. RESULTS: High-grade
clear cell RCC had significantly higher tumor size and lower PS than low grade.
Tumor size positively correlated with Fuhrman grade, but PS negatively did.
CONCLUSIONS: Tumor size and PS were significantly independent indexes for
differentiating high-grade from low-grade clear cell RCC.
PMID- 28686937
TI - Effective removal of phosphate from aqueous solution using humic acid coated
magnetite nanoparticles.
AB - Effective removal of excess phosphate from water is critical to counteract
eutrophication and restore water quality. In this study, low cost,
environmentally friendly humic acid coated magnetite nanoparticles (HA-MNP) were
synthesized and applied for the remediation of phosphate from aqueous media. The
HA-MNPs, characterized by FTIR, TEM and HAADF-STEM showed the extensive coating
of humic acid on the magnetite surface. The magnetic nanoparticles with diameters
of 7-12 nm could be easily separated from the reaction mixture by using a simple
hand held magnet. Adsorption studies demonstrate the fast and effective
separation of phosphate with maximum adsorption capacity of 28.9 mg/g at pH 6.6.
The adsorption behavior follows the Freundlich isotherm suggesting the formation
of non-uniform multilayers of phosphate on the heterogeneous surface of HA-MNP.
The adsorption kinetic fits the pseudo-second order model well with rate
constants of 0.206 +/- 0.003, 0.073 +/- 0.002 and 0.061 +/- 0.003 g mg-1min-1 for
phosphate (P) concentrations of 2, 5 and 10 mg/L respectively. The removal of
phosphate was found higher at acidic and neutral pH compared to basic conditions.
The nanoparticles exhibit good selectivity and adsorption efficiency for
phosphate in presence of co-existing ions such as Cl-, SO42-and NO3- with some
inhibition effect by CO32-. The effect of temperature on the adsorption reveals
that the process is endothermic and spontaneous. HA-MNPs are promising, simple,
environmentally friendly materials for the removal of phosphate from aqueous
media.
PMID- 28686938
TI - Quantitative proteomic analyses of the microbial degradation of estrone under
various background nitrogen and carbon conditions.
AB - Microbial degradation of estrogenic compounds can be affected by the nitrogen
source and background carbon in the environment. However, the underlying
mechanisms are not well understood. The objective of this study was to elucidate
the molecular mechanisms of estrone (E1) biodegradation at the protein level
under various background nitrogen (nitrate or ammonium) and carbon conditions (no
background carbon, acetic acid, or humic acid as background carbon) by a newly
isolated bacterial strain. The E1 degrading bacterial strain, Hydrogenophaga
atypica ZD1, was isolated from river sediments and its proteome was characterized
under various experimental conditions using quantitative proteomics. Results show
that the E1 degradation rate was faster when ammonium was used as the nitrogen
source than with nitrate. The degradation rate was also faster when either acetic
acid or humic acid was present in the background. Proteomics analyses suggested
that the E1 biodegradation products enter the tyrosine metabolism pathway.
Compared to nitrate, ammonium likely promoted E1 degradation by increasing the
activities of the branched-chain-amino-acid aminotransferase (IlvE) and enzymes
involved in the glutamine synthetase-glutamine oxoglutarate aminotransferase (GS
GOGAT) pathway. The increased E1 degradation rate with acetic acid or humic acid
in the background can also be attributed to the up-regulation of IlvE. Results
from this study can help predict and explain E1 biodegradation kinetics under
various environmental conditions.
PMID- 28686939
TI - Electric field induced salt precipitation into activated carbon air-cathode
causes power decay in microbial fuel cells.
AB - As a promising design for the real application of microbial fuel cells (MFCs) in
wastewater treatment, activated carbon (AC) air-cathode is suffering from a
serious power decay after long-term operation. However, the decay mechanism is
still not clear because of the complex nature of contaminations. Different from
previous reports, we found that local alkalinization and natural evaporation had
an ignorable effect on cathode performance (~2% decay on current densities),
while electric field induced salt precipitation (~53%) and biofouling (~37%) were
dominant according to the charge transfer resistance, which decreased power
desities by 36% from 1286 +/- 30 to 822 +/- 23 mW m-2 in 6 months. Biofouling can
be removed by scrapping, however, electric field induced salt precipitation under
biofilm still clogged 37% of specific area in catalyst layer, which was even seen
to penetrate through the gas diffusion layer. Our findings provided a new insight
of AC air-cathode performance decay, providing important information for the
improvement of cathodic longevity in the future.
PMID- 28686940
TI - Synergistic effect of water content and composite conditioner of Fenton's reagent
combined with red mud on the enhanced hydrogen production from sludge pyrolysis.
AB - This study investigated the synergistic effect of water content and a composite
conditioner of Fenton's reagent combined with red mud (Fenton-RM) on the
pyrolytic products (fuel gas, tar, and solid char) of deep-dewatered sludge. The
catalytic effect of metal oxides in Fenton-RM could be promoted by the presence
of water during sludge pyrolysis, showing higher gas yield with increased water
content. Maximum gas outputs of the deep-dewatered sludge conditioned with Fenton
RM (S-Fenton-RM) and the conventional dewatered sludge conditioned with
polyacrylamide (S-PAM), both appeared at 900 degrees C with a water content of
65 wt%, and were 0.257 and 0.189 L/g dry solid (DS), respectively. At the same
temperature and with the same water content, the hydrogen (H2) yields of the S
Fenton-RM samples were always higher than those of the S-PAM samples. At 900
degrees C, the maximum H2 yield of the S-Fenton-RM samples was 0.102 L/g DS,
which was 85.5% higher than that of the S-PAM samples. The results indicated that
water in the wet sludge provided the steam atmosphere for pyrolysis, and the
water vapor then involved in secondary cracking reformation of tar and char
gasification reactions, which would be catalyzed by the presence of metal oxides
in the Fenton-RM conditioner, thus increasing the yield of fuel gas, especially
hydrogen. The H2 production cost from the S-Fenton-RM system is less than that
from the S-PAM system. The results suggest that pyrolysis of the wet deep
dewatered sludge conditioned with Fenton-RM is an economical and promising
alternative for sewage sludge dewatering and disposal/reuse.
PMID- 28686941
TI - Diffusion and sorption of organic micropollutants in biofilms with varying
thicknesses.
AB - Solid-liquid partitioning is one of the main fate processes determining the
removal of micropollutants in wastewater. Little is known on the sorption of
micropollutants in biofilms, where molecular diffusion may significantly
influence partitioning kinetics. In this study, the diffusion and the sorption of
23 micropollutants were investigated in novel moving bed biofilm reactor (MBBR)
carriers with controlled biofilm thickness (50, 200 and 500 MUm) using targeted
batch experiments (initial concentration = 1 MUg L-1, for X-ray contrast media 15
MUg L-1) and mathematical modelling. We assessed the influence of biofilm
thickness and density on the dimensionless effective diffusivity coefficient f
(equal to the biofilm-to-aqueous diffusivity ratio) and the distribution
coefficient Kd,eq (L g-1). Sorption was significant only for eight positively
charged micropollutants (atenolol, metoprolol, propranolol, citalopram,
venlafaxine, erythromycin, clarithromycin and roxithromycin), revealing the
importance of electrostatic interactions with solids. Sorption equilibria were
likely not reached within the duration of batch experiments (4 h), particularly
for the thickest biofilm, requiring the calculation of the distribution
coefficient Kd,eq based on the approximation of the asymptotic equilibrium
concentration (t > 4 h). Kd,eq values increased with increasing biofilm thickness
for all sorptive micropollutants (except atenolol), possibly due to higher
porosity and accessible surface area in the thickest biofilm. Positive
correlations between Kd,eq and micropollutant properties (polarity and molecular
size descriptors) were identified but not for all biofilm thicknesses, thus
confirming the challenge of improving predictive sorption models for positively
charged compounds. A diffusion-sorption model was developed and calibrated
against experimental data, and estimated f values also increased with increasing
biofilm thickness. This indicates that diffusion in thin biofilms may be strongly
limited (f ? 0.1) by the high biomass density (reduced porosity).
PMID- 28686942
TI - Solutions to microplastic pollution - Removal of microplastics from wastewater
effluent with advanced wastewater treatment technologies.
AB - Conventional wastewater treatment with primary and secondary treatment processes
efficiently remove microplastics (MPs) from the wastewater. Despite the efficient
removal, final effluents can act as entrance route of MPs, given the large
volumes constantly discharged into the aquatic environments. This study
investigated the removal of MPs from effluent in four different municipal
wastewater treatment plants utilizing different advanced final-stage treatment
technologies. The study included membrane bioreactor treating primary effluent
and different tertiary treatment technologies (discfilter, rapid sand filtration
and dissolved air flotation) treating secondary effluent. The MBR removed 99.9%
of MPs during the treatment (from 6.9 to 0.005 MP L-1), rapid sand filter 97%
(from 0.7 to 0.02 MP L-1), dissolved air flotation 95% (from 2.0 to 0.1 MP L-1)
and discfilter 40-98.5% (from 0.5 - 2.0 to 0.03-0.3 MP L-1) of the MPs during the
treatment. Our study shows that with advanced final-stage wastewater treatment
technologies WWTPs can substantially reduce the MP pollution discharged from
wastewater treatment plants into the aquatic environments.
PMID- 28686943
TI - Determination of plutonium isotopes (238,239,240Pu) and strontium (90Sr) in
seafood using alpha spectrometry and liquid scintillation spectrometry.
AB - The present study was carried out to survey the levels of plutonium isotopes
(238,239,240Pu) and strontium (90Sr) in domestic seafood in Korea. In current,
regulatory authorities have analyzed radionuclides, such as 134Cs, 137Cs and
131I, in domestic and imported food. However, people are concerned about
contamination of other radionuclides, such as plutonium and strontium, in food.
Furthermore, people who live in Korea have much concern about safety of seafood.
Accordingly, in this study, we have investigated the activity concentrations of
plutonium and strontium in seafood. For the analysis of plutonium isotopes and
strontium, a rapid and reliable method developed from previous study was used.
Applicability of the test method was verified by examining recovery, minimum
detectable activity (MDA), analytical time, etc. Total 40 seafood samples were
analyzed in 2014-2015. As a result, plutonium isotopes (238,239,240Pu) and
strontium (90Sr) were not detected or below detection limits in seafood. The
detection limits of plutonium isotopes and strontium-90 were 0.01 and 1 Bq/kg,
respectively.
PMID- 28686944
TI - Cuckoos vs. top predators as prime bioindicators of biodiversity in disturbed
environments.
AB - We studied the abundance of the common cuckoo Cuculus canorus L. little cuckoo
Cuculus poliocephalus L. and Asian cuckoo Cuculus saturatus L. and avian top
predators as indicators of bird species richness (surrogate of biodiversity) in
disturbed environments caused by radioactive contamination in Chernobyl, Ukraine
and Fukushima, Japan, comparing their efficiency as indicators of local
biodiversity hotspots. Bird species richness and birds abundance were quantified
in each sample site during the breeding seasons between 2006 and 2015 and the
level of background radiation was measured at every site. The correlation between
number of cuckoos, top predators, land use composition and level of background
radiation with bird species richness as response variable were examined using
Generalized Linear Mixed Models. The strength of correlation between species
richness and abundance and the covariates obtained from the model outputs were
used as measure of the efficiency of each predictor, as well as the AIC of each
model. Background radiation was negatively correlated with bird species richness
and bird abundance in both countries, while number of top predators and cuckoos
were both positively correlated with bird species richness and abundance.
However, model with number of cuckoos was more performant than model with number
of avian top predators. These differences in performance supports the hypothesis
that cuckoos are a largely superior bioindicator than top predators.
PMID- 28686945
TI - Trophic transfer of 134Cs in the Manila clam Ruditapes philippinarum.
AB - Bioaccumulation of radiocaesium in many marine organisms occurs through complex
trophic transfer mechanisms. The present study addresses the trophic transfer of
134Cs in the widely distributed marine bivalve, the Manila clam Ruditapes
philippinarum, by experimentally determining the assimilation efficiency (AE) and
the specific role of food quality or diet on the AE in this marine invertebrate.
Pulse-chase feeding experiments were carried out on this clam using the
phytoplankton species Tetraselmis chuii, Phaeodactylum tricornutum and Isochrysis
galbana. Depuration kinetics of 134Cs over 21 days were analysed using a two
component exponential model. Observed assimilation efficiencies were consistently
less than 10% but slightly varied among individuals fed on the three different
phytoplankton species diets (T. chuii: AE = 8.4 +/- 0.6%; P. tricornutum: AE =
9.8 +/- 0.5%; I. galbana: AE = 5.3 +/- 0.6%), although no statistical differences
were observed. Comparing results from these experiments with existing data from
the literature on the same species exposed to caesium through seawater, it
appears that trophic transfer processes are the main accumulation pathway,
contributing up to 96% of the global 134Cs bioaccumulation in this bivalve
species.
PMID- 28686946
TI - Novel density-based and hierarchical density-based clustering algorithms for
uncertain data.
AB - Uncertain data has posed a great challenge to traditional clustering algorithms.
Recently, several algorithms have been proposed for clustering uncertain data,
and among them density-based techniques seem promising for handling data
uncertainty. However, some issues like losing uncertain information, high time
complexity and nonadaptive threshold have not been addressed well in the previous
density-based algorithm FDBSCAN and hierarchical density-based algorithm FOPTICS.
In this paper, we firstly propose a novel density-based algorithm PDBSCAN, which
improves the previous FDBSCAN from the following aspects: (1) it employs a more
accurate method to compute the probability that the distance between two
uncertain objects is less than or equal to a boundary value, instead of the
sampling-based method in FDBSCAN; (2) it introduces new definitions of
probability neighborhood, support degree, core object probability, direct
reachability probability, thus reducing the complexity and solving the issue of
nonadaptive threshold (for core object judgement) in FDBSCAN. Then, we modify the
algorithm PDBSCAN to an improved version (PDBSCANi), by using a better cluster
assignment strategy to ensure that every object will be assigned to the most
appropriate cluster, thus solving the issue of nonadaptive threshold (for direct
density reachability judgement) in FDBSCAN. Furthermore, as PDBSCAN and PDBSCANi
have difficulties for clustering uncertain data with non-uniform cluster density,
we propose a novel hierarchical density-based algorithm POPTICS by extending the
definitions of PDBSCAN, adding new definitions of fuzzy core distance and fuzzy
reachability distance, and employing a new clustering framework. POPTICS can
reveal the cluster structures of the datasets with different local densities in
different regions better than PDBSCAN and PDBSCANi, and it addresses the issues
in FOPTICS. Experimental results demonstrate the superiority of our proposed
algorithms over the existing algorithms in accuracy and efficiency.
PMID- 28686947
TI - Chicory fructans in pig diet reduce skatole in back fat of entire male pigs.
AB - Androstenone, skatole and indole are main compounds responsible for boar taint,
an off-odour in meat of some entire male pigs. Several feed ingredients derived
from chicory have been reported to reduce fat skatole levels, while results for
indole are more contradictory. The skatole-reducing effect is probably based on
the prebiotic effects described for fructan compounds. Inulin and oligofructose
have a high and low degree of polymerization, respectively. The fermentation rate
decreases with an increasing degree of polymerization, which may result in
differing effects of the compounds on skatole and/or indole levels. In this study
we evaluated the effect of the inclusion of 5% inulin or 5% oligofructose during
the last 3weeks before slaughter on carcass quality, concentration of skatole and
indole in back fat as well as on the olfactory evaluation of boar taint in fat.
Carcass weight did not differ between treatment groups but lean meat percentage
increased when feeding oligofructose (P=0.019) compared to the control group,
which is relevant for further research. Inclusion of 5% inulin or 5%
oligofructose in the finisher diet of entire male pigs significantly reduced the
back fat skatole concentration, without influence on indole. Olfactory score for
boar taint tended to decrease when oligofructose was added to the diet.
PMID- 28686948
TI - Posterior communicating artery aneurysms causing facial pain: A comprehensive
review.
AB - Posterior communicating aneurysms are commonly associated with oculomotor nerve
palsy. However, trigeminal nerve involvement among these aneurysms is a rare
event with no previous analysis. In order to describe the main features of
posterior communicating aneurysms causing trigeminal neuralgia (TGN-PComAAs)
eight cases (six from the literature plus two more illustrative cases) were
included in the present series. All cases were thoroughly studied in order to
collect their epidemiological, radiological, clinical, therapeutic, pathogenic,
and outcome data. The mean age at diagnosis was 57 years. Gender distribution
showed a female predominance (M-to-F ratio 3:5), while side distribution showed a
slight left dominance (62%). The aneurysms mean size was 24.7mm (range: 7-40mm).
In 7 cases (87.5%) the PComAA was reported to project posteriorly, associated
with cavernous sinus extension/compression in two of them and posterior fossa
extension in three. No case presented with hemorrhage. Facial pain was the
clinical onset in all eight cases, which was reported as an atypical TGN
(continuous with exacerbating fits) in 87.5%. Trigger points were absent in all
cases but one (87.5%). The most frequent anatomical distribution of the pain was
V2 alone (n=3), followed by V1-2 (n=2) and V1-2-3 (n=2). Three different
mechanisms for trigeminal neuralgia were observed, namely, cavernous sinus
compression (n=4), direct trigeminal root compression (n=3), and oculomotor nerve
compression (n=1). Three different treatment options were performed: surgery
(n=6), trigeminal thermo-rhizotomy (n=1) and medical management (n=1). According
to the Barrow Neurological Institute (BNI) score the pain control after main
treatment was I (no pain with no medication) in 7 cases (87.5%). The average
modified Rankin scale (mRS) score was 1. In sum, TGN-PComAAs are infrequent
lesions characterized by large size and posterior-medial-inferior projection.
They mainly cause atypical TGN, most commonly involving the first and second
trigeminal distributions (V1-V2). Surgical aneurysmal clipping has been the most
frequent treatment option for these aneurysms, providing good neurological
results in a vast majority and complete trigeminal pain relief in all cases.
PMID- 28686949
TI - Early maladaptive schemas and suicidal risk in an Iranian sample of patients with
obsessive-compulsive disorder.
AB - There are few studies on suicidal risk and its related factors in patients
diagnosed with obsessive-compulsive disorder (OCD). This study investigated the
associations of early maladaptive schemas, OC symptom dimensions, OCD severity,
depression and anxiety with suicidality (i.e., suicidal ideation and suicide
attempts) in OCD patients. Sixty OCD outpatients completed the Scale for Suicide
Ideation (SSI), the Young Schema Questionnaire-Short Form (YSQ-SF), the Yale
Brown Obsessive Compulsive Scale (Y-BOCS), the Dimensional Obsessive-Compulsive
Scale (DOCS) and the Depression Anxiety Stress Scales (DASS-21). 51.7% of
patients had lifetime suicide attempts and 75% had suicidal ideation. OCD
patients with lifetime suicide attempts exhibited significantly higher scores on
early maladaptive schemas than those without such attempts. Logistic regression
analysis revealed that the mistrust/abuse schema and the OC symptom dimension of
unacceptable thoughts explained lifetime suicide attempts. The mistrust/abuse
schema, unacceptable thoughts and depression significantly predicted suicidal
ideation. These findings indicated that the mistrust/abuse schema may contribute
to high suicidality in OCD patients. Also, patients suffering from unacceptable
thoughts need to be assessed more carefully for warning signs of suicide.
PMID- 28686950
TI - Residential proximity to agricultural fumigant use and IQ, attention and
hyperactivity in 7-year old children.
AB - OBJECTIVES: Our objective was to examine the relationship between residential
proximity to agricultural fumigant use and neurodevelopment in 7-year old
children. METHODS: Participants were living in the agricultural Salinas Valley,
California and enrolled in the Center for the Health Assessment of Mothers and
Children Of Salinas (CHAMACOS) study. We administered the Wechsler Intelligence
Scale for Children (4th Edition) to assess cognition and the Behavioral
Assessment System for Children (2nd Edition) to assess behavior. We estimated
agricultural fumigant use within 3, 5 and 8km of residences during pregnancy and
from birth to age 7 using California's Pesticide Use Report data. We evaluated
the association between prenatal (n = 285) and postnatal (n = 255) residential
proximity to agricultural use of methyl bromide, chloropicrin, metam sodium and
1,3-dichloropropene with neurodevelopment. RESULTS: We observed decreases of 2.6
points (95% Confidence Interval (CI): -5.2, 0.0) and 2.4 points (95% CI: -4.7,
0.2) in Full-Scale intelligence quotient for each ten-fold increase in methyl
bromide and chloropicrin use within 8km of the child's residences from birth to 7
years of age, respectively. There were no associations between residential
proximity to use of other fumigants and cognition or proximity to use of any
fumigant and hyperactivity or attention problems. These findings should be
explored in larger studies.
PMID- 28686951
TI - The association between total phthalate concentration and non-communicable
diseases and chronic inflammation in South Australian urban dwelling men.
AB - OBJECTIVE: To investigate associations between urinary total phthalate
concentration, chronic low-grade inflammation and non-communicable diseases in a
cohort of South Australian men. METHODS: 1504 men aged 39-84 years who provided a
urinary sample at the follow-up visit of the Men Androgen Inflammation Lifestyle
Environment and Stress (MAILES) study, a randomly-selected group of urban
dwelling, community-based men from Adelaide, Australia (n = 2038; study
participation rate: 78.1%). Total phthalate concentration was quantified in
fasting morning urine samples. Chronic diseases were assessed through self-report
questionnaire or directly measured using standardised clinical and laboratory
procedures. Inflammatory biomarkers were assayed by ELISA or spectroscopy.
Multivariable linear and logistic regression models were applied to determine
associations of log-transformed urinary phthalate concentration with inflammation
and chronic disease. RESULTS: Total phthalates were detected in 99.6% of urinary
samples; geometric mean (95% CI) was 114.1 (109.5-118.9)ug/g creatinine. Higher
total phthalate levels were associated with higher levels of hs-CRP, IL-6 (all p
< 0.05) and TNF-alpha but not MPO. Urinary total phthalate concentrations were
positively associated with cardiovascular disease, type-2-diabetes and
hypertension. Comparing extreme quartiles of total phthalate, prevalence ratios
were 1.78 (95% CI 1.17 - 2.71, p-trend = 0.001) for cardiovascular disease and
1.84 (95%CI 1.34 - 2.51, p-trend = 0.001) for type-2-diabetes and 1.14 (95%CI
1.01 - 1.29, p-trend = 0.013) for hypertension. Total phthalates and asthma and
depression were not significantly associated. CONCLUSION: A positive association
between total phthalates and cardiovascular disease, type-2-diabetes,
hypertension and increased levels of chronic low-grade inflammatory biomarkers
was observed in urban-dwelling Australian men.
PMID- 28686952
TI - Urban natural environments as nature-based solutions for improved public health -
A systematic review of reviews.
AB - Increasing urbanisation, changing disease scenarios, and current predictions of
climate change impacts require innovative strategies for providing healthy and
sustainable cities, now and in the future. The recently coined concept, Nature
based solutions (NBS), is one such strategy referring to actions that are
inspired by, supported by, or copied from nature, designed to address a range of
environmental challenges. The objective with this article is to evaluate the
evidence on public health benefits of exposure to natural environments and
explore how this knowledge could be framed within the NBS concept. We conducted a
systematic review of reviews following established methodology, including keyword
search in several databases, predefined inclusion criteria, and a data extraction
in accordance with the PICOS structure. We reviewed literature on associations
between public health and natural environments in relation to pathways -
sociobehavioural/cultural ecosystem services (e.g. stress and physical activity)
and regulating ecosystem services (e.g. heat reduction) - or defined health
outcomes (e.g. cardiovascular mortality). The results show that there is strong
evidence for improved affect as well as on heat reduction from urban natural
environments. These conditions may mediate the effect seen on cardiovascular
disease (CVD)-related mortality by exposure to natural environments. By also
reviewing existing literature on NBS and health, we phrase the results within the
NBS context, providing guidelines on how public health and well-being could be
integrated into implementation of NBS for resilient and liveable urban landscapes
and health in a changing climate.
PMID- 28686953
TI - Transport-related triplet states and hyperfine couplings in organic tandem solar
cells probed by pulsed electrically detected magnetic resonance spectroscopy.
AB - Tandem solar cells constitute the most successful organic photovoltaic devices
with power conversion efficiencies comparable to thin-film silicon solar cells.
Especially their high open-circuit voltage - only achievable by a well-adjusted
layer stacking - leads to their high efficiencies. Nevertheless, the microscopic
processes causing the lossless recombination of charge carriers within the
recombination zone are not well understood yet. We show that advanced pulsed
electrically detected magnetic resonance techniques such as electrically detected
(ED)-Rabi nutation measurements and electrically detected hyperfine sublevel
correlation (ED-HYSCORE) spectroscopy help to understand the role of triplet
excitons in these microscopic processes. We investigate fully working
miniaturised organic tandem solar cells and detect current-influencing doublet
states in different layers as well as triplet excitons located on the fullerene
based acceptor. We apply ED-HYSCORE in order to study the nuclear spin
environment of the relevant electron/hole spins and detect a significant amount
of the low abundant 13C nuclei coupled to the observer spins.
PMID- 28686954
TI - 2JHH-resolved HSQC: Exclusive determination of geminal proton-proton coupling
constants.
AB - The measurement of two-bond proton-proton coupling constants (2JHH) in prochiral
CH2 groups from the F2 dimension of 2D spectra is not easy due to the usual
presence of complex multiplet J patterns, line broadening effects and strong
coupling artifacts. These drawbacks are particularly pronounced and frequent in
AB spin systems, as those normally exhibited by the pair of diastereotopic CH2
protons. Here, a novel 2JHH-resolved HSQC experiment for the exclusive and
accurate determination of the magnitude of 2JHH from the doublet displayed along
the highly-resolved indirect F1 dimension is described. A pragmatic 2JHH NMR
profile affords a fast overview of the full range of existing 2JHH values. In
addition, a 2JHH/delta(13C)-scaled version proves to be an efficient solution
when severe signal overlapping complicate a rigorous analysis. The performance of
the method is compared with other current techniques and illustrated by the
determination of challenging residual dipolar 2DHH coupling constants of small
molecules dissolved in weakly orienting media.
PMID- 28686955
TI - Targeting STAT3 with silibinin to improve cancer therapeutics.
AB - Signal transducer and activator of transcription 3 (STAT3) has a prominent role
in mediating resistance to conventional chemo-/radio-therapies and modern
targeted drugs. While a number of STAT3 inhibitors have been shown to enhance the
efficacy of therapeutic agents in vitro, the majority of them have yet to enter
clinical evaluation mostly because of lack of efficacy issues. Silibinin is the
main component of the silymarin complex, a standardized extract obtained from the
seeds of the milk thistle herb Silybum marianum. This review summarizes current
evidence supporting the ability of silibinin to function as a natural down
modulator of STAT3 activity. We examine the reported capacity of silibinin to
reduce the toxicity of cancer treatments and to reverse tumor cell resistance via
STAT3 inhibition. We also briefly review our clinical data in cancer patients
treated with oral nutraceutical products containing silibinin. The beneficial
effects of silibinin might accelerate the design of strategies aimed to overcome
and prevent the emergence of STAT3-mediated cancer drug resistance in clinical
settings.
PMID- 28686956
TI - Evaluation of a collaborative project to develop sustainable healthcare education
in eight UK medical schools.
AB - INTRODUCTION: Environmental change poses pressing challenges to public health and
calls for profound and far-reaching changes to policy and practice across
communities and health systems. Medical schools can act as a seedbed where
knowledge, skills and innovation to address environmental challenges can be
developed through innovative and collaborative approaches. OBJECTIVES: The
objectives of this study were to (1) explore drivers and challenges of
collaboration for educational development between and within medical schools; (2)
evaluate the effectiveness of a range of pedagogies for sustainable healthcare
education; and (3) identify effective strategies to facilitate the renewal of
medical curricula to address evolving health challenges. STUDY DESIGN:
Participatory action research. METHODS: Medical school teams participated in a
nine-month collaborative project, including a one-day seminar to learn about
sustainable healthcare education and develop a project plan. After the seminar,
teams were supported to develop, deliver and evaluate new teaching at their
medical school. RESULTS: New teaching was introduced at seven medical schools. A
variety of pedagogies were represented. Collaboration between schools motivated
and informed participants. The main challenges faced related to time pressures.
Educators and students commented that new teaching was enjoyable and effective at
improving knowledge and skills. CONCLUSIONS: Collaborative working supported
educators to develop and implement new teaching sessions rapidly and effectively.
Collaboration can help to build educators' confidence and capacity in a new area
of education development. Different forms of collaboration may be appropriate for
different circumstances and at different stages of education development.
PMID- 28686957
TI - On the state of crystallography at the dawn of the electron microscopy
revolution.
AB - While protein crystallography has, for many years, been the most used method for
structural analysis of macromolecular complexes, remarkable recent advances in
high-resolution electron cryo-microscopy led to suggestions that 'the revolution
will not be crystallised'. Here we highlight the current success rate, speed and
ease of modern crystallographic structure determination and some recent triumphs
of both 'classical' crystallography and the use of X-ray free electron lasers. We
also outline fundamental differences between structure determination using X-ray
crystallography and electron microscopy. We suggest that crystallography will
continue to co-exist with electron microscopy as part of an integrated array of
methods, allowing structural biologists to focus on fundamental biological
questions rather than being constrained by the methods available.
PMID- 28686958
TI - Exorcising the ghost of the Sputnik crisis.
AB - Drug calculation is not immune to the undesirable impact of math anxiety and
negative attitudes on test outcomes in nursing studies, and several studies
indicate that math anxiety is present in the student population at such a degree
that it is likely to interfere with these students' mathematical ability.
Examining the educational system through the lens of history and adding a dash of
cultural theory, a contributing cause to the math anxiety may be found in the
Sputnik Crisis of the late 1950s, the ghostly remnants of which are still present
in the stereotypes of mathematics promoted by mass media. In an effort to reshape
the culturally conditioned attitudes which may be responsible for math anxiety,
we suggest using elements from popular culture to diversify the perception and
image of mathematics in drug calculation.
PMID- 28686959
TI - The effectiveness of a simulated scenario to teach nursing students how to
perform a bed bath: A randomized clinical trial.
AB - BACKGROUND: Simulation allows students to develop several skills during a bed
bath that are difficult to teach only in traditional classroom lectures, such as
problem-solving, student interactions with the simulator (patient), reasoning in
clinical evaluations, evaluation of responses to interventions, teamwork,
communication, security and privacy. OBJECTIVES: This study aimed to evaluate the
effectiveness of a simulated bed bath scenario on improving cognitive knowledge,
practical performance and satisfaction among nursing students. DESIGN: Randomized
controlled clinical trial. SETTING: Nursing students that were in the fifth
period from two educational institutions in Brazil. PARTICIPANTS: Nursing
students (n=58). METHOD: The data were collected using the assessments of
cognitive knowledge, practical performance and satisfaction were made through a
written test about bed baths, an Objective Structured Clinical Examination (OSCE)
and a satisfaction questionnaire. RESULTS: We identified that the acquisition and
assimilation of cognitive knowledge was significantly higher in the simulation
group (p=0.001). The performance was similar in both groups regardless of the
teaching strategy (p=0.435). At follow-up, the simulation group had significantly
more satisfaction with the teaching method than the control group (p=0.007).
CONCLUSION: The teaching strategy based on a simulated scenario of a bed bath
proved to be effective for the acquisition of cognitive knowledge regarding bed
baths in clinical practice and improved student satisfaction with the teaching
process.
PMID- 28686960
TI - Photodynamic therapy with TMPyP - Porphyrine induces mitotic catastrophe and
microtubule disorganization in HeLa and G361 cells, a comprehensive view of the
action of the photosensitizer.
AB - Photodynamic therapy (PDT) is a useful tool against cancer and various other
diseases. PDT is capable to induce different cell death mechanisms, due to the
PDT evoked reactive oxygen species (ROS) production and is dose dependent. It is
known that cytoskeleton is responsible for numerous cell functions, including
cell division, maintenance of cell shape, their adhesion ability and movement.
PDT initiated redistribution and subsequent disintegration of cytoskeletal
components that precedes cell death. Here was present our results in HeLa and
G361 cells subjected to sublethal PDT treatments using alpha,beta,chi,delta
porphyrin-Tetrakis (1-methylpyridinium-4-yl) p-Toluenesulfonate porphyrin
(TMPyP). The photosensitizer (PS) induced transient increasing of mitotic index
(MI) observable early after PDT, cell cycle arrest, microtubule (MTs)
disorganization of interphase cells, aberrant mitosis and formation of rounded
cells with partial loss of adherence. Some cells were partly resistant to PDT
induced MTs disorganization. The differences between both cell lines to PDT
response were described. This is the first evidence of TMPyP - PDT induced
microtubule disorganization and the cell death mechanisms known as mitotic
catastrophe and the first detail analysis of microtubule aberrations of mitotic
and interphase cells in HeLa and G361 cell lines. New modification of techniques
of protein immunolabeling was developed.
PMID- 28686961
TI - Towards substrate-independent age estimation of blood stains based on
dimensionality reduction and k-nearest neighbor classification of absorbance
spectroscopic data.
AB - The age determination of blood traces provides important hints for the
chronological assessment of criminal events and their reconstruction. Current
methods are often expensive, involve significant experimental complexity and
often fail to perform when being applied to aged blood samples taken from
different substrates. In this work an absorption spectroscopy-based blood stain
age estimation method is presented, which utilizes 400-640nm absorption spectra
in computation. Spectral data from 72 differently aged pig blood stains (2h to
three weeks) dried on three different substrate surfaces (cotton, polyester and
glass) were acquired and the turnover-time correlations were utilized to develop
a straightforward age estimation scheme. More precisely, data processing includes
data dimensionality reduction, upon which classic k-nearest neighbor classifiers
are employed. This strategy shows good agreement between observed and predicted
blood stain age (r>0.9) in cross-validation. The presented estimation strategy
utilizes spectral data from dissolved blood samples to bypass spectral artifacts
which are well known to interfere with other spectral methods such as reflection
spectroscopy. Results indicate that age estimations can be drawn from such
absorbance spectroscopic data independent from substrate the blood dried on.
Since data in this study was acquired under laboratory conditions, future work
has to consider perturbing environmental conditions in order to assess real-life
applicability.
PMID- 28686963
TI - Long-term health consequences of recessions during working years.
AB - Economic crises may have severe consequences for population health. We
investigate the long-term effects of macroeconomic crises experienced during
prime working age (20-50) on health outcomes later in life using SHARE data
(Survey of Health Aging and Retirement in Europe) from eleven European countries.
Analyses are based on the first two waves of SHARE data collected in 2004 and
2006 (N = 22,886) and retrospective life history data from SHARELIFE collected in
2008 (N = 13,732). Experiencing a severe crisis in which GDP dropped by at least
1% significantly reduces health later in life. Specifically, respondents hit by
such a shock rate their subjective health as worse, are more likely to suffer
from chronic diseases and mobility limitations, and have lower grip strength. The
effects are twice as large among low-educated respondents. A deeper analysis of
critical periods in life reveals that respondents' health is more affected by
crises experienced later in the career (between age 41 and 50). The labor market
patterns show that these people drop out of the labor force. While men retire
early, women are more likely to become home makers. In line with the literature
on the negative consequences of retirement on health, this suggests that early
retirement in times of economic crises might be detrimental to health.
PMID- 28686962
TI - Forensic aspects of homicides by insulin overdose.
AB - Analysis of homicidal insulin overdose is a challenging task in forensic practice
because of the difficulties in toxicological analysis as well as the elusive
pathologic changes. We performed a detailed histopathologic examination on four
autopsy cases involving insulin homicide, using H&E, immunohistochemistry (IHC)
and immunofluorescence assays. Severe reactive astrocyte proliferation was
obvious in the white matter of the cerebrum, corpus callosum, cerebellum and
brain stem, especially in subcortical regions. We found a statistically
significant increase in the number and total area of reactive astrocytes compared
with controls (p<0.001). Insulin was detected at the injection sites of
subcutaneous soft tissues by using IHC, luminescence immunoassay and
immunofluorescence. Most insulin deposits were located in the gaps between
adipocytes, and a few deposits were located in peripheral nerves and inflammatory
cells. We also detected protamine in the skin tissues in two of the four cases.
Our study revealed that the presence of insulin and/or protamine at the injection
sites, along with severe reactive astrocyte proliferation, could help diagnose
insulin overdose.
PMID- 28686964
TI - Relative importance of 13 correlates of child stunting in South Asia: Insights
from nationally representative data from Afghanistan, Bangladesh, India, Nepal,
and Pakistan.
AB - Optimal growth and development in early childhood is determined by a complex
interplay of child, maternal, household, environmental, and socioeconomic factors
that influence nutritional intake, but interventions to reduce child
undernutrition sometimes target specific risk factors in isolation. In this
analysis, we assess the relative importance of 13 correlates of child stunting
selected based on a collective review of existing multi-factorial frameworks:
complementary feeding, breastfeeding, feeding frequency, dietary diversity,
maternal height, body mass index (BMI), education, age at marriage, child
vaccination, access to improved drinking source and sanitation facilities,
household indoor air quality, and household wealth. The analytic sample consisted
of nationally representative cross-sectional surveys from the most recent
Demographic and Health Surveys for Bangladesh (2014), India (2005), Nepal (2011),
and Pakistan (2013), and from the National Nutrition Survey for Afghanistan
(2013). In the mutually adjusted logistic regression model for 3,159 infants aged
6-8 months, short maternal stature (OR: 2.93; 95% CI: 1.93-4.46) and lack of
complementary foods (OR: 1.47; 95% CI: 1.12-1.93) were associated with
significantly higher risk of stunting. For 18,586 children aged 6-23 months, the
strongest correlates of child stunting were: maternal height (OR: 3.37, 95% CI:
2.82-4.03), household wealth (OR: 2.25, 95% CI: 1.72-2.94), maternal BMI (OR:
1.59, 95% CI: 1.27-2.00), minimum dietary diversity (OR: 1.48, 95% CI: 1.27
1.72), maternal education (OR: 1.36, 95% CI: 1.18-1.56), and age at marriage (OR:
1.17, 95% CI: 1.05-1.30). Full vaccination and minimum dietary frequency were
also found to be important for severe stunting for children of this age group.
Some differences were found in the relative ordering and statistical significance
of the correlates in country-specific analyses. Our findings indicate that
comprehensive strategies incorporating a broader progress on socioeconomic
conditions as well as investments in nutrition specific programs are needed to
improve child undernutrition in South Asia.
PMID- 28686965
TI - Chemical constituents and pharmacological actions of carob pods and leaves
(Ceratonia siliqua L.) on the gastrointestinal tract: A review.
AB - Carob tree, Ceratonia siliqua L., is a medicinal plant used in Tunisian
traditional medicine for the treatment of the gastro-intestinal (GI) disorders.
In this respect, a relatively large number of scientific publications on the
carob tree have been published in recent years. Therefore, the present review was
aimed to analyze the traditional uses, phytochemical constituents and
pharmacological activities of Ceratonia siliqua on the GI tract. Indeed, previous
investigations on the carob pods and leaves have revealed the presence of a
number of compounds including high amounts of carbohydrates, dietary fibers,
minerals, polyphenols, flavonoids and low amounts of protein and lipids. This
plant possesses anti-inflammatory, antimicrobial, anti-diarrheique, antioxidant,
anti-ulcer, anti-constipation and anti-absorptive of glucose activities in the
gastrointestinal tract. Based on the chemical and pharmacological characteristics
of C. siliqua, we concluded that this species has beneficial preventive and
therapeutic properties, especially, in digestive tract.
PMID- 28686966
TI - Pectolinarigenin from the leaves of Clerodendrum volubile shows potent
immunomodulatory activity by inhibiting T - cell proliferation and modulating
respiratory oxidative burst in phagocytes.
AB - There have been increasing interest in the use of plant-derived substance as
immunomodulators for the treatment and management of inflammatory ailments.
Clerodendrum volubile, a leafy vegetable is known for its folkloric applications
in the treatments of several inflammatory related ailments, but with little
scientific evidence. This study reports the isolation, structure elucidation and
in vitro immunomodulatory potentials of pectolinarigenin from C. volubile leaves.
The immunomodulatory potentials of the crude methanolic extract and fractions [n
hexane (Hex), dichloromethane (DCM), ethyl acetate (EtOAc) and n - butanol
(BuOH)] were investigated on whole blood, neutrophil and macrophage phagocytic
respiratory burst using luminol-amplified chemiluminescence technique. DCM
fraction showed higher inhibitory activity on respiratory burst, indicating high
suppressive immunomodulatory potency. The DCM fraction was further fractionated
using a gravity column chromatography loaded with silica gel. The column was
eluted with mixtures of Hex and DCM (92.5:7.5) in increasing order of polarity up
to Hex: DCM (88:12) to afford 5,7-Dihydroxy-6,4'-dimethoxyflavone
(pectolinarigenin). The structure of the compound was established using data
obtained from 1H- and 13C NMR spectroscopies and mass spectrometry. The isolated
flavone was investigated for its inhibitory activity of neutrophil phagocytes
respiratory burst as well as T - Cell proliferation. The compound exhibited
significant activities (at p <0.05) indicating high suppressive immunomodulatory
potency. The potent suppressive effect of pectolinarigenin on polymorphonuclear
neutrophils (PMNs) respiratory oxidative burst and T - cell proliferation
suggests an immunomodulatory potential and pathway of the flavonoid.
PMID- 28686967
TI - The anti-inflammatory and antinociceptive activity of albumins from Crotalaria
retusa seeds.
AB - Seeds of Crotalaria retusa L. are used in popular medicine because of their
pharmacological properties. The albumin fraction obtained from its seeds contains
lectin, a protein known to have analgesic and anti-inflammatory properties. Thus,
albumins extracted from C. retusa were investigated for their anti-inflammatory
and antinociceptive effects. The intraperitoneal administration of different
doses of albumins (5, 10 or 20mg/kg) significantly inhibited the mice paw edema
induced by carrageenan (maximum inhibition rate of 80.9% at four hours, 20mg/kg),
and this event was followed by diminishing paw myeloperoxidase measurements.
Albumins (20mg/kg) also inhibited neutrophil migration into the peritoneal cavity
induced by carrageenan. However, no effect was observed in the dextran-induced
paw edema and abdominal contortions induced by acetic acid. Moreover, albumins
(20mg/kg) significantly reduced the second (inflammatory) phase of the licking
time induced by formalin. The detection of heammaglutinating activity against
human erythrocytes in albumins evidences the presence of lectin in seeds of C.
retusa. Our data showed that seeds of C. retusa had anti-inflammatory and
antinociceptive properties and such activities are probably due to the inhibitory
effect on neutrophil migration of lectin present in albumins.
PMID- 28686968
TI - Neuroprotective effect of Indian propolis in beta-amyloid induced memory deficit:
Impact on behavioral and biochemical parameters in rats.
AB - The study aimed at the investigation of neuroprotective activity of macerated
ethanolic extract of Indian propolis (MEEP) against beta-Amyloid 25-35 (Abeta25
35) induced memory impairment in Alzheimer's disease. MEEP was administrated
orally to Wistar rats at doses of 100, 200 and 300mg/kg. Behavioral performances
were evaluated using morris water maze and radial arm maze. At the end of
behavioral study, the brains were removed and antioxidant parameters and brain
monoamines were estimated. Further acetylcholinesterase (AchE) inhibition and
brain-derived neurotropic factor (BDNF) were evaluated. In addition hematological
parameters and histopathological tests were also carried out. In behavioral
models, MEEP significantly (P<0.05) reversed the cognitive impairment of beta
amyloid-induced rats. The antioxidant potential was significantly increased
(P<0.05) after administration of MEEP. Malondialdehyde levels were significantly
(P<0.01) decreased in brain homogenate after treatment with MEEP extract as
compared with diseased control group (group III). MEEP showed dose-dependent AChE
inhibition and increased the levels of brain monoamines (P<0.05) as compared with
group III. MEEP improved memory deficits by increasing BDNF in plasma (P<0.05).
The study concludes that MEEP has anti-Alzheimer potential in rats through
multiple mechanisms and further studies are ongoing for fractionation and
biological screening.
PMID- 28686969
TI - MiR-30c-5p suppresses migration, invasion and epithelial to mesenchymal
transition of gastric cancer via targeting MTA1.
AB - BACKGROUND: In China, gastric cancer (GC) is an ordinary malignant tumor. Recent
literatures have shown that microRNA is critical during tumorigenesis. This study
focuses on the influence of miR-30c-5p on the metastasis of GC and further
explores its underlying mechanism. METHODS: Before the study, expression level of
miR-30c-5p and targeted protein was detected in 40 GC tissue samples and 5 GC
cells by RT-qPCR. Meanwhile, correlation analysis was conducted between miR-30c
5p expression level and clinicopathological features. In addition, wound healing
assay and cell invasion assay were utilized to identify whether miR-30c-5p could
affect the migrated and invaded ability of GC cells. Western blotting assay and
luciferase assay were used to explore the potential mechanism. RESULTS: In GC
tissues, miR-30c-5p expression level was significantly lower and was remarkably
related with clinical features such as tumor node metastasis(TNM) stage and
lymphatic metastasis. Moreover, the migrated and invaded ability of GC cells was
enhanced through knockdown of miR-30c-5p, while overexpression of miR-30c-5p
presented with reversed effect. Further study showed that miR-30c-5p inhibited
the expression of its target spot, metastasis-associated protein 1(MTA1), and
then suppressed the process of epithelial to mesenchymal transition(EMT) which
was important in the metastasis of GC. CONCLUSION: The results indicate that miR
30c-5p, a novel suppressor in tumorigenesis, could inhibit the metastasis and EMT
via MTA1, which may offer a possible therapeutic target in GC.
PMID- 28686970
TI - Endocytic pathways of optimized resveratrol cubosomes capturing into human
hepatoma cells.
AB - Resveratrol (RSV) is a natural polyphenolic compound with high affinity to
hepatocytes. It has numerous benefits as anticancer, antioxidant,
immunomodulatory and cardioprotective actions. Nevertheless, RSV therapeutic
applications are hindered by its low solubility, light sensitivity and extensive
first-pass metabolism. Cubosomes are colloidally stable dispersed liquid
crystalline nanoparticles. The incorporation of RSV into cubosomes could overcome
some of its physicochemical limitations. A Design-Expert(r) software was applied
to optimize cubosomes in terms of particle size and encapsulation efficiency
(EE%). The used model proved its suitability in predicting optimum cubosomal
size. The prepared cubosomes showed an enhanced HepG2 cytotoxicity except at
particle size of ~20nm. Different endocytic pathways mechanisms as
macropinocytosis, clathrin-mediated endocytosis and caveolae-mediated endocytosis
were identified in the cellular uptake of RSV cubosomes depending on particle
size. Caveolae-mediated transport was shown to have a significant effect on RSV
cubosomes internalization efficiency and cytotoxicity.
PMID- 28686971
TI - GAS5 knockdown reduces the chemo-sensitivity of non-small cell lung cancer
(NSCLC) cell to cisplatin (DDP) through regulating miR-21/PTEN axis.
AB - Non-small cell lung cancer (NSCLC), known as the most common type of lung cancer,
has caused great economic losses and brought the patients with NSCLC great
suffering. The NSCLC chemo-resistance to cisplatin (DDP) -based chemotherapy
remains a huge challenge. The lncRNA growth arrest-specific 5 (GAS5) has been
reported to be related with cancers including NSCLC. Phosphatase and tensin
homolog (PTEN) has been frequently reported to affect chemo-sensitivity of
cancers, and usually acts as a tumor suppressor. In this paper, we demonstrated a
significant low GAS5expression in NSCLC patients was correlated with poorer
clinicopathologic features; GAS5 knockdown by si-GAS5 transfection promoted NSCLC
cell viability. Additionally, GAS5 was involved in the regulation of chemo
sensitivity of the NSCLC cell to DDP through regulation of PTEN pathway. LncRNAs
commonly exerts their functions through the interaction with miRNAs. According to
previous studies, miR-21 acts as an oncogenic miRNA through targeting PTEN in
many cancers. In the present study, GAS5 could compete with PTEN for miR-21
binding. We further verified that the interaction between GAS5 and miR-21 was
required in the regulation of NSCLC chemo-sensitivity to DDP through PTEN
pathway. Taken together, the data of the present study demonstrated a novel
mechanism by which GAS5/miR-21/PTEN affects the sensitivity of NSCLC to DDP-based
therapy.
PMID- 28686972
TI - Peptide nucleic acids (PNAs): currently potential bactericidal agents.
AB - In recent years, the emergence of ESBL-producing and multi-drug resistant
bacteria have been increased and designing novel components is necessary for
confrontation these bacteria. Peptide nucleic acids (PNAs) are one of the
synthetic components that bind to single strand DNA and RNA. Applications of
these components are wide while, and one of the important applications of these
components is inhibition of gene expression and knock downing the target gene
follow as inhibition of bacterial growth. For PNA targeting gene, peptide-PNAs
(PPNA) activity cannot be occurred without sequence homology, at the same time,
it has been affected by sequence-based specific target and dose-dependent-based
manner. Choosing the conserved sequence in different bacterial genus can provide
broad-spectrum antimicrobial activity. In this review article, we studied several
research papers and extract PNA targeting genes that cause gene knock down and
inhibition of bacterial growth. Some novel opportunities for advancement and the
design ultra-narrow-spectrum antimicrobial drugs against multi-drug can be
accessible by utilizing PNA against necessary genes of pathogens. These results
open novel vision for therapeutic intervention. Future researches are required to
evaluate the safety, toxicity and pharmacokinetics properties of PPNAs in order
to be utilized in clinical treatment.
PMID- 28686973
TI - Protective effects of tropisetron on cerulein-induced acute pancreatitis in mice.
AB - Acute pancreatitis (AP) causes morbidity and mortality. The aim of the present
study was to investigate the protective effect of tropisetron against AP induced
by cerulein. Cerulein (50MUg/kg, 5 doses) was used to induce AP in mice. Six
hours after final cerulein injection, animals were decapitated.
Hepatic/pancreatic enzymes in the serum, pancreatic content of malondialdehyde
(MDA), pro-inflammatory cytokines and myeloperoxidase (MPO) activity were
measured. Tropisetron significantly attenuated pancreatic injury markers and
decreased the amount of elevated serum amylase, lipase, alanine aminotransferase
(ALT), aspartate aminotransferase (AST), MPO activities and pro-inflammatory
cytokines levels caused by AP in mice. Tropisetron didn't affect the pancreatic
levels of MDA. Our results suggest that tropisetron could attenuate cerulein
induced AP by combating inflammatory signaling. Further clinical studies are
needed to confirm its efficacy in patients with AP.
PMID- 28686974
TI - Phytotherapeutic potential of natural herbal medicines for the treatment of mild
to-severe atopic dermatitis: A review of human clinical studies.
AB - For many decades, natural herbal medicines, polyherbal formulations and/or
decoctions of plant-derived materials have widely been accepted as alternative
complementary therapies for the treatment, cure or prevention of a wide range of
acute and chronic skin diseases including chronic herpes, prurigo, acute and
chronic wounds, psoriasis and atopic dermatitis (AD). This review was aimed to
summarize and critically discuss about the therapeutic viability and clinical
applicability of natural herbal medicines for the treatment of AD in human. The
critical analysis of the literature revealed that oral (in the form of capsules,
syrup or granules) and/or topical application (alone or in conjunction with wet
wrap dressing and/or acupuncture) of natural herbal medicines exhibit remarkable
potential for the treatment of mild-to-severe AD in adults, children, infants and
in the pregnant women. In this review, the clinical efficacy of various herbal
formulations such as Chinese herbal therapies, Korean medicines, Iranian
medicines, honey, natural herbal oils (coconut oil, olive oil and mineral oil),
beeswax, dodder seeds and whey for the treatment of AD has been discussed. The
clinical anti-AD efficacy of these complementary therapies has been observed in
terms of down-regulation in Scoring Atopic Dermatitis (SCORAD) index, erythematic
intensity, Children's Dermatology Life Quality Index (CDLQI), Dermatology Life
Quality Index (DLQI), pruritus and itching frequency, transepidermal water loss
(TEWL) and expression of AD-mediated chemokines. Conclusively, we recognized that
natural herbal medicines demonstrate remarkable clinical efficacy when used alone
or in conjunction with other complementary therapies for the treatment of AD in
patients of all ages as well as pregnant women.
PMID- 28686975
TI - Overexpression of low-density lipoprotein receptors stimulated by vascular
endothelial growth factor in fibroblasts from pterygium.
AB - The activation of subconjunctival fibroblasts is believed to be responsible for
the pathogenesis of pterygium. Vascular endothelial growth factor (VEGF) appears
to be the most potent stimulator of formation and progression of pterygium.
Pterygium excision is a common procedure, although the recurrence rates remain
high. Various postoperative adjuvant therapies are now attempted to lower the
recurrence rate, with severe side effects. To offer a greater therapeutic effect
and lower side effects, it's necessary to discover a constant nanoparticle drug
delivery targeting to subconjunctival fibroblasts in pterygium (PSFs). This study
was designed to investigate the expression of low-density lipoprotein receptor
(LDLr) stimulated by VEGF in PSFs. We found that after exposure to VEGF, mRNA and
protein levels of LDLr were both increased significantly in PSFs, assessed using
relative quantitative real-time RT-PCR and Western blot. Moreover, it's
demonstrated that the expression of LDLr were positively correlated with the
cells proliferation. Uptake of DiI-LDL via live PSFs was increased with time,
estimated by confocal microscopy. The protein expression of LDLr in pterygium
subconjunctival tissues was significantly higher than in normal subconjunctival
tissues. These results suggest that LDLr in the activated PSFs may become a novel
target receptor for controlled drug delivery to lower postsurgical recurrence
rate.
PMID- 28686976
TI - Chronic consumption of Hypericum humifusum leaf extracts impairs epididymis
spermatozoa characters in association with oxidative stress in adult male Wistar
rats.
AB - Recently, there has been increasing interest in Hypericum (Hypericaceae) genus.
The first part of the present study focused on the phytochemical analysis of the
methanolic and aqueous extracts of Hypericum humifusum leaves. The second part of
the study investigated the effect of Hypericum humifusum leaf extracts on male
reproductive parameters. 30 male rats were grouped into control (1mL/rat,
distilled water), treated by 200mg/kg body weight (bw) aqueous extract (A200),
400mg/kg bw aqueous extract (A400), 10mg/kg bw methanolic extract (M10) and
20mg/kg bw methanolic extract (M20) groups. The phytochemical analysis revealed
the presence of tannins, flavonoids, steroids, carbohydrates, and phenolic
compounds. After thirty-day treatment, body and reproductive organs were weighed.
Testes in all rat groups were processed for biochemical assays and
histopathological examinations. Epididymis sperm analyses were also performed.
Testicular tissue homogenate samples were used for Malondialdehyde (MDA),
catalase and superoxide dismutase (SOD) measurements. We showed that Hh extracts
induced a severe seminiferous tubular damage with an increase in the percentage
of empty seminiferous tubules. Epididymis sperm analysis revealed a significant
reduction in density and viability of sperm with alteration of spermatozoa
morphology. Also, we found that Hh leaf extracts decreased plasma total
cholesterol, HDL-cholesterol and triglycerides levels. These results were
associated with an increase of MDA levels and a decrease of catalase and SOD
activities in testis tissues. Our finding revealed that chronic consumption of Hh
extracts induces disruption of normal spermatogenesis by alteration of sperm
density, viability, and morphology. This action may be due to an inhibition of
the antioxidant-defense system.
PMID- 28686978
TI - Sinapic acid modulates Nrf2/HO-1 signaling pathway in cisplatin-induced
nephrotoxicity in rats.
AB - BACKGROUND: Cisplatin-induced nephrotoxicity is related to increased reactive
oxygen species and inflammatory cytokines in the kidney. Sinapic acid (SA) has
both antioxidant and anti-inflammatory activities. AIMS: We determined the
effects of SA on cisplatin-induced nephrotoxicity in rats, and the potential
mechanisms by which it augments antioxidant responses and attenuates
nephrotoxicity related to oxidative/nitrosative stress, apoptosis, and
inflammation. METHODS: Kidney function markers (i.e., serum urea, uric acid,
creatinine, and lactate dehydrogenase), oxidative stress markers (i.e., lipid
peroxidation and nitric oxide), antioxidant systems (i.e., superoxide dismutase,
catalase, and reduced glutathione), inflammation markers (i.e., tumor necrosis
factor-alpha [TNF-alpha], interleukin-6 [IL-6], and myeloperoxidase [MPO]),
apoptotic markers (caspase 3, Bax, and Bcl-2), and the levels of nuclear factor
kappaB (NF-kappaB [p65]), Nrf2, and heme oxygenase-1 (HO-1) were assessed.
Histopathological examinations of the kidney were also used to evaluate cisplatin
induced nephrotoxicity. KEY FINDINGS: SA (10 and 20mg/kg) pretreatment
ameliorated kidney function, upregulated antioxidant levels, and downregulated
lipid peroxidation and nitric oxide levels in cisplatin-injected rats, resulting
in significant reductions in oxidative stress and replenishment of endogenous
antioxidant enzymes. Cisplatin upregulated cytokines (i.e., TNF-alpha and IL-6)
and MPO, increased apoptosis, and downregulated Nrf2 and HO-1. SA pretreatment
downregulated the pro-apoptotic caspase-3 and Bax proteins, and upregulated the
anti-apoptotic Bcl-2 protein. SA pretreatment also alleviated the extent of
histological impairment and reduced neutrophil infiltration in renal tubules.
SIGNIFICANCE: The results suggest that the Nrf2/HO-1 signaling pathway may be the
primary target for protection from cisplatin-induced nephrotoxicity by SA, and
that SA reduces oxidative stress, inflammation, and apoptosis by inhibiting NF
kappaB.
PMID- 28686977
TI - Cardioprotective effect of the xanthones from Gentianella acuta against
myocardial ischemia/reperfusion injury in isolated rat heart.
AB - Gentianella acuta (Michx.) Hulten is widely used for the treatment of arrhythmia
and coronary heart disease in Ewenki Folk Medicinal Plants and Mongolian
Medicine, popularly known as "Wenxincao" in China. To investigate the potential
protective role of the xanthones from G. acuta against myocardial I/R injury in
isolated rat heart and its possible related mechanism. The protective role of
xanthones on myocardial I/R injury was studied on Langendorff apparatus. The
hemodynamic parameters including the left ventricular developed pressure (LVDP),
the maximum rate of up/down left intraventricular pressure (+/-dp/dtmax),
coronary flow (CF) and heart rate (HR) were recorded during the perfusion. The
results demonstrated that the xanthones from G. acuta treatment significantly
improved myocardial function (LVDP, +/-dp/dtmax and CF), increased the levels of
superoxide dismutase (SOD) and catalase (CAT), succinate dehydrogenase (SDH),
malate dehydrogenase (MDH), ATP and the ratio of glutathione and glutathione
disulfide (GSH/GSSG), whereas suppressed the levels of Lactate dehydrogenase
(LDH), creatine kinase (CK) and malondialdehyde (MDA). Furthermore, the xanthones
upregulate the level of Bcl-2 protein and downregulate the level of Bax protein.
These results indicated that xanthones from G. acuta exhibited cardioprotective
effects on myocardial I/R injury through its activities of anti-oxidative effect
and anti-apoptosis effect.
PMID- 28686979
TI - High mannose N-glycan binding lectin from Remusatia vivipara (RVL) limits cell
growth, motility and invasiveness of human breast cancer cells.
AB - Breast cancer known for its high metastatic potential is responsible for large
mortality rate amongst women; hence it is imperative to search for effective anti
metastatic molecules despite anticancer drugs. The current study describes the
potential of Remusatia vivipara lectin (RVL), inducing apoptosis in breast cancer
cells there by limiting motility and invasiveness. RVL binds to the cell surface
glycans of MDA-MB-468 and MCF-7 cells, exhibiting strong glycan mediated
cytotoxic effect, but show marginal effect on non-tumorigenic MCF-10A cells. RVL
elicits increased cellular stress, apoptotic vacuoles and nuclear disintegration
in both MDA-MB-468 and MCF-7 cells accompanied by depletion of G0/G1, S and G2/M
phases. Lectin interaction induced production of reactive oxygen species through
altering mitochondrial membrane potential progressing to apoptosis. Further, RVL
strongly elicited reproductive cell death in MDA-MB-468 cells and showed strong
inhibitory effect on neovascularization demonstrated in chorioallantoic membrane
assay. Treatment of MDA-MB-468 cells with RVL, suppress the motility and invasive
property as shown by scratch wound heal and Boyden chamber transwell assays
respectively. These results provide an insight into significance of interaction
of RVL with specific cell surface high mannose N-glycans resulting in curtailing
the metastatic ability of cancer cells.
PMID- 28686980
TI - Whewell on classification and consilience.
AB - In this paper I sketch William Whewell's attempts to impose order on
classificatory mineralogy, which was in Whewell's day (1794-1866) a confused
science of uncertain prospects. Whewell argued that progress was impeded by the
crude reductionist assumption that all macroproperties of crystals could be
straightforwardly explained by reference to the crystals' chemical constituents.
By comparison with biological classification, Whewell proposed methodological
reforms that he claimed would lead to a natural classification of minerals, which
in turn would support advances in causal understanding of the properties of
minerals. Whewell's comparison to successful biological classification is
particularly striking given that classificatory biologists did not share an
understanding of the causal structure underlying the natural classification of
life (the common descent with modification of all organisms). Whewell's key
proposed methodological reform is consideration of multiple, distinct principles
of classification. The most powerful evidence in support of a natural
classificatory claim is the consilience of claims arrived at through distinct
lines of reasoning, rooted in distinct conceptual approaches to the target
objects. Mineralogists must consider not only elemental composition and chemical
affinities, but also symmetry and polarity. Geometrical properties are central to
what makes an individual mineral the type of mineral that it is. In Whewell's
view, function and organization jointly define life, and so are the keys to
understanding what makes an organism the type of organism that it is. I explain
the relationship between Whewell's teleological account of life and his natural
theology. I conclude with brief comments about the importance of Whewell's
classificatory theory for the further development of his philosophy of science
and in particular his account of consilience.
PMID- 28686981
TI - Differentiation between decomposed remains of human origin and bigger mammals.
AB - This study is a follow-up study in the search for a human specific marker in the
decomposition where the VOC-profile of decomposing human, pig, lamb and roe
remains were analyzed using a thermal desorber combined with a gas chromatograph
coupled to a mass spectrometer in a laboratory environment during 6 months. The
combination of 8 previously identified human and pig specific compounds (ethyl
propionate, propyl propionate, propyl butyrate, ethyl pentanoate, 3-methylthio-1
propanol, methyl(methylthio)ethyl disulfide, diethyl disulfide and pyridine) was
also seen in these analyzed mammals. However, combined with 5 additional
compounds (hexane, heptane, octane, N-(3-methylbutyl)- and N-(2
methylpropyl)acetamide) human remains could be separated from pig, lamb and roe
remains. Based on a higher number of remains analyzed, as compared with the pilot
study, it was no longer possible to rely on the 5 previously proposed esters to
separate pig from human remains. From this follow-up study reported, it was found
that pyridine is an interesting compound specific to human remains. Such a human
specific marker can help in the training of cadaver dogs or in the development of
devices to search for human remains. However, further investigations have to
verify these results.
PMID- 28686982
TI - Efficacy of biofeedback on quality of life in stages I and II pelvic organ
prolapse: A Pilot study.
AB - OBJECTIVES: Pelvic organ prolapse (POP) is a prevalent disorder which seriously
affects the sufferer's quality of life. The main goal of this study was to
evaluate biofeedback impact on quality of life in women with mild to moderate
POP. STUDY DESIGN: 40 females in stages I and II POP were allocated into 2
groups. One group received pelvic floor muscle exercise and lifestyle advice in
addition to biofeedback twice a week for 4 weeks, while the other received a
lifestyle advice sheet and pelvic floor muscle exercise without biofeedback. A
valid Persian version of P-QOL questionnaire was applied to assess the patients
quality of life at baseline, 4 weeks and 12 weeks follow up. Pressure biofeedback
and Physical examination were also performed in order to determine pelvic floor
muscle strength and staging of the prolapse, respectively. Collected data were
analyzed by mixed ANOVA test using SPSS 22. RESULTS: Biofeedback improved the
quality of life in seven of nine P-QOL domains. However, it had no significant
impact either on pelvic floor muscle strength or on the stage of the prolapse.
CONCLUSION: Biofeedback could be considered as a non-invasive treatment leading
to quality of life promotion in women with stages I and II POP.
PMID- 28686983
TI - Chronophysiological features of the normal mineral composition of human saliva.
AB - BACKGROUND: The high rate of changes in the composition of saliva can be used for
the monitoring of various biorhythms in order to study the physiological
characteristics of the human body. RESEARCH OBJECTIVE: The study of the dynamics
of the near-24-h mineral composition of saliva in men and women. METHODS: The
study involved 20 men and 20 women, age 23.1+/-0.9years. Saliva samples were
collected every 3h during the day within 10min. The mineral composition of saliva
was defined by the capillary electrophoresis technique. The cross-group
differences were evaluated using the non-parametric criterion. RESULTS: It was
shown that the maximum values of the mineralizing capacity fall to 7-8 a.m. and
18-19p.m., which is due to the change in the rate of saliva secretion. The near
24-h dynamics of the saliva pH practically coincides with the dynamics of the
Ca/P ratio; there are evident maxima at 9:00 am and 15-18p.m. The values of the
Na/K ratio are out of phase with the Ca/P ratio. There is one maximum,
corresponding to 3 am in the night, and one minimum at 12-13p.m., which is due to
a decreased level of sodium and increased potassium concentration. Statistically
valid differences between men and women in pH (p<0.001), concentrations of
inorganic phosphorus (p<0.001), as well as Ca/P coefficient (p=0.011) were
identified. CONCLUSION: The dynamics of the studied parameters during 24h is
characterized by pronounced intervals.
PMID- 28686985
TI - Somatic health care utilization by patients treated for substance use disorders.
AB - INTRODUCTION: Patients with substance use disorder (SUD) are frequently suffering
from co-occurring somatic disorders, increasing the risk of mortality. Somatic
health care utilization (sHCU) often remains unknown to the physician during SUD
treatment. This paper analyses sHCU and associated costs among patients in SUD
treatment compared to matched, non-substance dependent controls. METHODS: Health
care utilization data on 4972 SUD patients were matched to 19,846 controls by
gender, birth year and ethnic origin. Subcategories of patients were formed based
on SUD and on co-morbid psychiatric disorder. Data on sHCU during the year prior
to the last treatment contact (the 'index date') for both patients and their
matched controls were extracted from a health insurance database. RESULTS:
Patients had a higher sHCU (with increased associated costs) than controls,
especially when alcohol dependence was involved. In particular, sHCU for
cardiovascular, respiratory, infectious diseases, injuries and accidents was
increased among patients. However, the use of preventive medication, such as
lipid-lowering drugs, is lower among SUD patients. Co-morbidity of psychiatric
disorders led to further increase of sHCU, whereas patients with comorbid non
affective psychotic disorder (NAPD) showed lower sHCU and costs. CONCLUSION:
Patients with SUD overall have a high sHCU, associated with high costs. There are
indications that SUD patients have less access to preventive medication. Patients
with comorbid NAPD are at risk of possible underutilization of somatic health
care. Furthermore, we conclude that these larger administrative databases allow
for comparisons between various diagnostic categories.
PMID- 28686984
TI - Influence of STRO-1 selection on osteogenic potential of human tooth germ derived
mesenchymal stem cells.
AB - Mesenchymal stem cells derived from the human tooth germ (hTGSCs) are a
heterogeneous cell population that can differentiate into osteogenic, neurogenic,
and adipogenic lineages. The aim of this study was to compare the osteogenic
differentiation capacity of STRO-1 positive (STRO-1+) hTGSCs and unsorted
heterogeneous hTGSCs and to establish if STRO-1+ cells are more committed to
osteogenic differentiation. HTGSCs were isolated from impacted third molar tooth
germ tissues of adolescents, and a subpopulation of STRO-1+ hTGSCs was obtained
by fluorescence-activated cell sorting. STRO-1+, STRO-1 negative (STRO-1-), and
unsorted cells were cultured in osteogenic and standard culture media to compare
their capacity to differentiate towards osteoblastic lineage. Cells were tested
for proliferation rates, alkaline phosphatase activity, and amounts of
accumulated calcium. Gene expression levels of the RUNX2, osteocalcin, and
osteonectin genes were analyzed with real time PCR. Mineralization and osteogenic
protein expression were examined by using von Kossa staining and confocal
microscopy. Our results indicated that osteogenically induced cell populations
showed greater mineralization capacity than non-induced cells. However,
expression levels of early and late osteogenic markers were not significantly
different between STRO-1+ and unsorted cells. In conclusion, the selection by
STRO-1 expression does not yield cells with osteogenic capacity higher than that
of the heterogeneous hTGSC population. Cell sorting using osteogenic markers
other than STRO-1 might be beneficial in obtaining a more sensitive osteogenic
sub-population from unsorted heterogenous hTGSCs.
PMID- 28686986
TI - Illicit drug consumption in school populations measured by wastewater analysis.
AB - BACKGROUND: Analysis of student consumption of illicit drugs (ID) by school
population surveys (SPS) provides information useful for prevention, but the
results may be influenced by subjective factors. We explored wastewater (WW)
analysis to improve the information. METHODS: We used WW analysis to measure ID
consumption in eight secondary schools in Italy in 2010-13 (students aged 15-19).
Samples were collected from the sewage pipes of the schools during lessons for
one week each year. Samples were analysed by mass spectrometry to measure ID and
consumption by students was compared to that of the general population. RESULTS:
We found THCCOOH (human metabolite of THC) concentrations in 2010 indicating
significant consumption of cannabis in all the schools and benzoylecgonine (human
metabolite of cocaine) suggesting a limited consumption of cocaine in all but one
school. Morphine was only found in traces, and amphetamine, methamphetamine,
ecstasy, ketamine and mephedrone were not detectable. Repeated analysis showed
cannabis stable until 2012 with increases in 2013, low cocaine and morphine
levels, and none of the other ID. DISCUSSION: WW analysis suggested that students
used amounts of cannabis comparable to the general population, with low, sporadic
use of cocaine and opioids, but excluded the use of significant amounts of
amphetamine, methamphetamine, ecstasy, ketamine and mephedrone. WW analysis was
useful to confirm SPS figures and provides complementary findings for effective
prevention strategies. This is the first time WW analysis has been used to
investigate consumption of a large number of ID and new psychoactive substances
(NPS) in schools.
PMID- 28686987
TI - Morning administration of oral methamphetamine dose-dependently disrupts
nighttime sleep in recreational stimulant users.
AB - INTRODUCTION: Use of amphetamine-type stimulants (e.g., methamphetamine) is
associated with acute sleep disruptions. No prior reports have characterized the
acute effects of methamphetamine on sleep using polysomnography, the gold
standard for objective sleep monitoring. METHODS: Recreational stimulant users
(n=19) completed a baseline assessment, which included questionnaires assessing
demographic and substance use characteristics, and the Pittsburgh Sleep Quality
Index (PSQI), which assesses sleep quality over the past month. Participants were
administered 0mg (placebo), 20mg, or 40mg oral methamphetamine at 08:15h on study
days, using a double-blind, randomized, within-subjects design. Sleep was
monitored using polysomnography from 22:20 that evening until 06:15 the following
morning. RESULTS: PSQI scores indicated more than half of participants reported
poor sleep quality at baseline. Methamphetamine dose-dependently increased sleep
latency, and decreased total sleep time, sleep efficiency, time in NREM 2 sleep,
number of REM periods, and total time in REM sleep. Sleep under placebo
conditions was consistent with what would be expected from healthy adults.
CONCLUSIONS: Morning oral administration of methamphetamine produces robust
disruptions in nighttime sleep. Future research should examine relations between
stimulant use and sleep disruption in naturalistic settings, with regard to both
stimulant abuse and licit prescription use.
PMID- 28686988
TI - Prevalence, correlates, comorbidity and treatment of electronic nicotine delivery
system use in the United States.
AB - INTRODUCTION: This study presents nationally representative data on the
prevalence, correlates, psychiatric comorbidity and treatment (including
pharmacological and nonpharmacological) among electronic nicotine delivery system
(ENDS) users. METHODS: Face-to-face interviews in the National Epidemiologic
Survey on Alcohol and Related Conditions-III. RESULTS: Prevalences of 12-month
and lifetime ENDS use were 3.8% (SE=0.14) and 5.4% (SE=0.17). Odds of ENDS use
were greater among men than women, regardless of timeframe. Rates were lower
among Blacks, Hispanics and Asians/Pacific Islanders relative to Whites. Odds of
12-month and lifetime ENDS use was also higher among younger (<65years) than
older (>=65years) individuals and higher among individuals with high school
education relative to these with some college education. Odds of 12-month and
lifetime ENDS use was also higher among individuals with incomes <$70,000.00
compared with those with incomes>=$70,000.00 and higher among the previously
married relative to those who were currently married. Associations between 12
month ENDS use and severe nicotine use disorder were strong, whereas associations
with other substance use disorders and borderline and antisocial personality
disorders were modest (AORs=1.3-2.6). Rates of treatment seeking to cut down or
quit tobacco or nicotine use (12-month, 25.0% (SE=1.6); lifetime, 24.4% (SE=1.4))
were low. CONCLUSIONS: ENDS use is substantially comorbid, especially with
nicotine use disorder. Virtually all ENDS users smoked cigarettes. Research is
needed to understand their role in smoking cessation, adverse effects on bodily
systems and their potential for addiction and comorbidity.
PMID- 28686989
TI - Mixed-amphetamine salts expectancies among college students: Is stimulant induced
cognitive enhancement a placebo effect?
AB - INTRODUCTION: Non-medical use of prescription stimulants for cognitive
enhancement in college students is increasing, despite evidence showing little
benefit in non-clinical populations. The balanced placebo design (BPD) was used
to independently evaluate the pharmacologic versus expectancy effects of mixed
amphetamine salts on cognitive performance among a non-clinical sample of college
aged students. METHOD: Participants were screened and excluded for ADHD and other
psychopathologies. A non-clinical sample (N=32) completed four two-hour
laboratory sessions and were administered a neurocognitive battery in each
session. Medication Assignment (10mg mixed-amphetamine salt (AdderallTM) versus
placebo) was crossed with Instructional Set (deception versus truth). A within
subjects design was used, such that all participants experienced each of the four
conditions of the BPD during one of the four laboratory sessions. RESULTS:
Participants performed no better than chance in identifying whether they received
stimulant or placebo (Belief about Medication Assignment; 47% agreement; kappa=
0.047, p=0.590). Participants showed improvement on only two of 31 subtests
during active medication. Expecting and receiving stimulants was associated with
improved cognitive performance. However, expecting placebo was associated with
worse cognitive performance, regardless of the type of medication given.
DISCUSSION: This study demonstrated that although non-medical use of stimulants
does not enhance cognition, expectancies prominently influence cognitive
performance. Participants who believed they received active medication both
subjectively rated themselves as performing better and objectively performed
better on a minority of subtests, independent of medication state.
PMID- 28686990
TI - Left frontal pole theta burst stimulation decreases orbitofrontal and insula
activity in cocaine users and alcohol users.
AB - BACKGROUND: Preclinical research has demonstrated a causal relationship between
medial prefrontal cortex activity and cocaine self-administration. As a step
towards translating those data to a neural circuit-based intervention for
patients, this study sought to determine if continuous theta burst stimulation
(cTBS) to the left frontal pole (FP), would attenuate frontal-striatal activity
in two substance-dependent populations. METHODS: Forty-nine substance dependent
individuals (25 cocaine, 24 alcohol) completed a single-blind, sham-controlled,
crossover study wherein they received 6 trains of real or sham cTBS (110% resting
motor threshold, FP1) each visit. Baseline evoked BOLD signal was measured
immediately before and after real and sham cTBS (interleaved TMS/BOLD imaging:
single pulses to left FP; scalp-to-cortex distance covariate, FWE correction
p<0.05) RESULTS: Among cocaine users, real cTBS significantly decreased evoked
BOLD signal in the caudate, accumbens, anterior cingulate, orbitofrontal (OFC)
and parietal cortex relative to sham cTBS. Among alcohol users, real cTBS
significantly decreased evoked BOLD signal in left OFC, insula, and lateral
sensorimotor cortex. There was no significant difference between the groups.
CONCLUSIONS: These data suggest that 6 trains of left FP cTBS delivered in a
single day decreases TMS-evoked BOLD signal in the OFC and several cortical nodes
which regulate salience and are typically activated by drug cues. The reliability
of this pattern across cocaine- and alcohol-dependent individuals suggests that
cTBS may be an effective tool to dampen neural circuits typically engaged by
salient drug cues. Multiday studies are required to determine it this has a
sustainable effect on the brain or drug use behavior.
PMID- 28686991
TI - Contribution to the improvement of diatom-based assessments of the ecological
status of large rivers - The Sava River Case Study.
AB - The Sava River Basin is a major drainage basin of southeastern Europe,
significantly influenced by anthropogenic activities. Our study was focused on
diatom communities as an indicator of the ecological status of running waters. We
investigated over 937km of the Sava River at 19 sampling sites. Benthic diatom
communities and 17 diatom indices were analyzed along with a large set of
environmental parameters. CCA revealed that the most important elements along the
spatial gradient were As and Si. Our results show that the species Navicula
recens (Lange-Bert.) Lange-Bertalot and Eolimna minima (Grunow) Lange-Bertalot
are very abundant at downstream localities where the highest concentrations of As
were measured. The number of motile diatoms increased along the nutrient
gradient, i.e. with Si availability. Correlations between diatom indices and
selected environmental factors showed that temperature, As, Si and Fe are in
significant negative correlation with most diatom indices. Analysis revealed the
influence of As and metals in water on diatoms, although their concentrations did
not exceed environmental standards. While our findings do not confirm that diatom
indices reveal the intensity of pressures solely caused by nutrient and/or
organic pollutants, they suggest that in moderately polluted large rivers benthic
diatoms are good bioindicators of multiple pressures, and that diatom indices
could serve as indicators of the level of overall degradation of an ecosystem.
PMID- 28686992
TI - Reactive nitrogen losses from China's food system for the shared socioeconomic
pathways (SSPs).
AB - Food production in China has been changing fast as a result of socio-economic
development. This resulted in an increased use of nitrogen (N) in food
production, and also to increased reactive nitrogen (Nr) losses to the
environment, causing nitrogen pollution. Our study is the first to quantify
future Nr losses from China's food system for the Shared Socio-economic Pathways
(SSPs). We show that Nr losses differ largely among SSPs. We first qualitatively
described the five SSP storylines for China with a focus on food production and
consumption. Next, we interpreted these SSP scenarios quantitatively for 2030 and
2050, using the NUFER (NUtrient Flows in Food chains, Environment and Resources
use) model to project the Nr losses from China's food system. The results
indicate that Nr losses from future food system in China are relatively low for
SSP1 and SSP2, and relatively high for SSP3 and SSP4. In SSP5 Nr losses from
China's food system are projected to be slightly lower than the level of today.
PMID- 28686993
TI - Potentially toxic elements in water and sediments of the Sava River under extreme
flow events.
AB - River ecosystems are exposed to various stressors. Among them, elements may
contribute to overall pollution of riverine environments, in particular during
the extreme flow events. To evaluate the influence of variable river flow
conditions on the mobilization of potentially toxic elements (PTE) (Cr, Ni, Cd,
Zn, Pb, As and Cu) from sediments into the overlaying waters of the Sava River,
samples were collected in September 2014, during extremely high water discharges
and in September 2015, under low water discharge conditions. In water samples the
total element concentrations and the dissolved element contents (<0.45MUm) were
determined. Sediment pollution was estimated by determination of the total
element concentrations and mobile element fraction (0.11molL-1 acetic acid).
Anthropogenic inputs of elements to sediments were evaluated by normalizing
elemental against Al concentration. The results showed that concentrations of PTE
in water were in general higher during high water discharges, while the soluble
concentrations were higher during low water level conditions. Concentrations of
PTE in the Sava sediments collected in 2015 were lower than those collected in
2014, mainly because during the extreme floods a mixture of bank sediment
material and contaminated soil was sampled. Partitioning coefficients between
suspended particulate matter (SPM) and soluble content of elements in the water
under high and low flow conditions, indicated on different affinity of elements
to SPM in relation to different flow regimes. The potential ecological risk posed
by the simultaneous presence of PET in sediments was evaluated by Probable Effect
Concentration Coefficient (PEC-Q) approach. Under high water level conditions,
PEC-Qs were all above critical value 0.34 and derived mostly from anthropogenic
inputs of Cr and Ni. Overall sediment toxicity was much lower under low water
discharges. The data from this study importantly contribute to the knowledge
regarding the behaviour of PTE under extreme flow events.
PMID- 28686994
TI - Quantitative and qualitative changes in antibiotic resistance genes after passing
through treatment processes in municipal wastewater treatment plants.
AB - In this study, quantitative and qualitative changes in antibiotics resistance
genes (ARGs) were investigated in two municipal wastewater treatment plants
(WWTPs) treating pretreated livestock or industrial wastewater as well as
municipal sewage. Total eight ARGs (tetX, tetM, tetA, sul1, sul2, ermB, qnrD, and
blaTEM) were quantified, and their relative abundance was assessed by ARGs
copies/16S rRNA gene copies. The fate of ARGs was observed to be different
between two WWTPs: sul, qnrD, and blaTEM were proliferated during the treatment
processes only in the WWTP1 which received pretreated livestock wastewater.
Furthermore, dynamic shifts in patterns of ARGs occurrence were observed during
biological, secondary sedimentation and coagulation processes. During biological
treatment in both WWTPs, relative abundance of tet and ermB changed: tet
increased significantly by 211.6-357.6%, while ermB decreased by 70.4-92.0%.
Little variation was observed in sul, qnrD and blaTEM. Subsequently, the relative
abundance of tet decreased during the secondary sedimentation and coagulation in
both WWTPs: tet decreased by 56.0-86.3% during sedimentation and by 48.2-75.7%
during coagulation, respectively. During the final treatment, different responses
of antibiotic resistance bacteria (ARB) and ARGs to ultraviolet (UV) disinfection
were found: removal efficiencies of ARB were observed in the range of 34-75%,
while obvious reduction in ARGs was not observed at the UV dose of 27mJ/cm2.
Although ARGs underwent various treatment processes, considerable levels of ARGs
remained at discharge amounting to 4.2*1018 copies/day from WWTP1 and 5.4*1016
copies/day from WWTP2, respectively.
PMID- 28686995
TI - A polyamidoamine dendrimer-streptavidin supramolecular architecture for biosensor
development.
AB - A novel polyamidoamine dendrimer-streptavidin supramolecular architecture
suitable as a versatile platform for biosensor development is reported. The
dendrimer was electrodeposited on a glassy carbon electrode via cyclic
voltammetry. The dendrimer electrode was further modified with streptavidin by
electrostatic attraction upon drop coating. The platform i.e. the dendrimer
streptavidin modified electrode was electrochemically interrogated in phosphate
buffer, ferrocyanide and H2O2. The dendrimer-streptavidin platform was used in
the preparation of a simple DNA biosensor as a proof of concept. The
supramolecular architecture of dendrimer-streptavidin was stable, electroactive
and thus lends itself as a versatile immobilisation layer for any biotinylated
bioreceptors in biosensor development.
PMID- 28686996
TI - Anti-cancer gold(I) phosphine complexes: Cyclic trimers and tetramers containing
the P-Au-P moiety.
AB - We report the application of cationic tri- and tetra-nuclear gold(I) phosphine
complexes [Au3(MU-dppen)3]X3 and [Au4(MU-dppa)4]X4 (X=OTf, PF6)
[OTf=trifluoromethanesulfonate, dppen=trans-1,2-bis(diphenylphosphino)ethene,
dppa=bis(diphenylphosphino)acetylene] for cancer treatment. The results of
cytotoxicity tests on four different cancer cells [prostate (DU145), cervical
(HeLa), breast (MDAMB-231) and fibro sarcoma (HT1080)] indicate these complexes
possess remarkable tumor cell growth inhibitory effects and high selectivity
towards cancer cells. The anti-tumor mechanism of the tri- and tetra-nuclear
gold(I) complexes has also been investigated.
PMID- 28686997
TI - Management of epilepsy in MERRF syndrome.
AB - Myoclonic epilepsy with ragged-red fibers (MERRF) syndrome is a rare syndromic
mitochondrial disorder (MID) with a broad phenotypic but narrow genotypic
heterogeneity. One of the predominant phenotypic features in addition to myopathy
is epilepsy. The most frequent seizure type in MERRF is generalised myoclonic
seizure but also focal myoclonic, focal atonic, generalised tonic-clonic,
generalised atonic, generalised myoclonic-atonic, typical absences, or tonic
clonic seizures of unknown onset have been reported. There are no guidelines
available for the management of epilepsy in MERRF syndrome but several expert
opinions and general recommendations for the treatment of mitochondrial epilepsy
have been published. According to these recommendations the antiepileptic drugs
(AEDs) of choice are levetiracetam, topiramate, zonisamide, piracetam, and
benzodiazepines. Perampanel has not been applied in MERRF patients but is
promising in non-mitochondrial myoclonic epilepsy. Mitochondrion-toxic agents,
including mitochondrion-toxic AEDs, such as valproate, carbamazepine, phenytoin,
and barbiturates, should be avoided as well as AEDs potentially enhancing the
frequency of myoclonus, such as phenytoin, carbamazepine, lamotrigine,
vigabatrin, tiagabine, gabapentin, pregabalin, and oxcarbazepine.
PMID- 28686998
TI - Development and validity of methods for the estimation of temporal gait
parameters from heel-attached inertial sensors in younger and older adults.
AB - The heel is likely a suitable location to which inertial sensors are attached for
the detection of gait events. However, there are few studies to detect gait
events and determine temporal gait parameters using sensors attached to the
heels. We developed two methods to determine temporal gait parameters: detecting
heel-contact using acceleration and detecting toe-off using angular velocity data
(acceleration-angular velocity method; A-V method), and detecting both heel
contact and toe-off using angular velocity data (angular velocity-angular
velocity method; V-V method). The aim of this study was to examine the concurrent
validity of the A-V and V-V methods against the standard method, and to compare
their accuracy. Temporal gait parameters were measured in 10 younger and 10 older
adults. The intra-class correlation coefficients were excellent in both methods
compared with the standard method (0.80 to 1.00). The root mean square errors of
stance and swing time in the A-V method were smaller than the V-V method in older
adults, although there were no significant discrepancies in the other
comparisons. Our study suggests that inertial sensors attached to the heels,
using the A-V method in particular, provide a valid measurement of temporal gait
parameters.
PMID- 28686999
TI - School poverty effects on trajectories of child behaviour: Do they depend on
gender and ethnicity?
AB - This study examined English school poverty effects on trajectories of child
behaviour across ages 3, 5, 7 and 11, and the moderating roles of ethnicity and
gender. School poverty predicted internalising and externalising problems
concurrently, and internalising problems longitudinally. In poor schools, girls
had a steeper incline in internalising problems, but made greater reductions in
externalising problems. Ethnic differences were also found in the association
between school poverty and child adjustment. Gender and ethnic background may
influence how a child responds emotionally and behaviourally to the composition
of peers at school.
PMID- 28687000
TI - Correction: Early age decline in DNA repair capacity in the liver: in depth
profile of differential gene expression.
PMID- 28687023
TI - Adrenalectomy for incidentaloma: lessons learned from a single-centre series of
274 patients.
AB - BACKGROUND: Adrenal incidentalomas are increasingly diagnosed and include a wide
spectrum of lesions from benign adenomas to secreting or malignant lesions. The
aim of the present study is to report a large single-institution experience of
patients undergoing surgery for adrenal incidentaloma with particular attention
to their diagnosis and post-operative course and the evolution of surgical
practice over time. METHODS: From 1993 to 2013, 274 patients underwent
adrenalectomy for incidentaloma. All patients underwent standardized clinical,
hormonal and imaging assessments. RESULTS: Patients were mainly female (63.1%; n
= 173), and the median age of patients was 56.5 years. After a complete hormonal
evaluation, 47.9% (n = 129) of incidentalomas were classified as secreting
tumours, including 24.4% (n = 67) subclinical cortisol-secreting adenomas and
18.9% (n = 52) pheochromocytomas. Adrenocortical carcinomas represented 9.5% (n =
26) of incidentalomas, and the risk of malignancy was significantly correlated
with tumour size. The conversion rate after laparoscopic adrenalectomy (90.9%; n
= 249) was 3.2% (n = 8). The overall morbidity rate was 13.9%, which included a
4.4% rate of severe morbidity (Clavien-Dindo >=3). From 2008 onwards, there was a
significant decrease (P < 0.001) in the use of surgical approaches for non
secreting adenomas. CONCLUSION: After a complete work-up, half of the
incidentalomas were classified as subclinical oversecreting adrenal lesions and
10% proved to be malignant adrenocortical carcinomas. The debatable use of
surgical approaches for benign nonfunctioning adenomas significantly decreased
over time.
PMID- 28687024
TI - Brain metastases from colorectal cancer: characteristics and management.
AB - BACKGROUND: Brain metastases (BMs) are the most common intracranial neoplasms in
adults, but they rarely arise from colorectal cancer (CRC). The objective of this
study was to report an overview of the characteristics and current management of
CRC BMs. METHODS: A systematic review on CRC BMs was performed using Medline
database from 1983 to 2015. The search was limited to studies published in
English. Review articles, not relevant case report or studies or studies relating
to animal and in vitro experiments were excluded. RESULTS: BMs occurred in 0.06
4% of patients with CRC. Most BMs were metachronous and were associated with lung
(27-92%) and liver (12-80%) metastases. Treatment options depended on the number
of BMs, the general conditions of the patient and the presence of other
metastases. Most frequent treatment was whole-brain radiotherapy (WBRT) alone
(36%), with median overall survival comprised between 2 and 9 months. Median
overall survival was better after surgery alone (from 3 to 16.2 months), or
combined with WBRT (from 7.6 to 14 months). After stereotactic radiosurgery
alone, overall survival could reach 9.5 months. Many favourable prognostic
factors were identified, such as high Karnofsky performance status, low recursive
partitioning analysis classes, lack of extracranial disease, low number of BMs
and possibility to perform surgical treatment. CONCLUSION: BMs from CRC are rare.
In the presence of favourable prognostic factors, an aggressive management
including surgical resection with or without WBRT or stereotactic radiosurgery
can improve the overall survival.
PMID- 28687025
TI - Prognostic value of positron emission tomography/computed tomography for adjuvant
chemotherapy of colon cancer.
AB - BACKGROUND: To assess the prognostic value of preoperative 18 F
fluorodeoxyglucose positron emission tomography/computed tomography in patients
with high-risk stage II or stage III colon cancer who underwent FOLFOX
chemotherapy. METHODS: The study included 166 patients with high-risk stage II or
stage III colon cancer who received FOLFOX4 chemotherapy. Retrospective patient
data were analysed including pathological stage, histology, disease-free survival
(DFS) and the maximum standardized uptake value (SUVmax ) of the primary tumour
on 18 F-fluorodeoxyglucose positron emission tomography/computed tomography. The
primary end point was DFS. RESULTS: There were recurrences in 29 of the 166
patients (17.4%). Measuring the area under the receiver operating characteristic
curve, the cut-off value of SUVmax with maximum sensitivity and specificity was
10.95. Using the Kaplan-Meier method, the DFS of the patients categorized by
SUVmax tended to differ (P = 0.055). In univariate analyses, the risk factors for
DFS were age over 70 years, higher N stage and neural invasion. SUVmax <= 10.95
showed a tendency, but was not significant (P = 0.0604). In multivariate
analyses, the risk factors for DFS were age over 70 and neural invasion.
CONCLUSIONS: The results of this study suggest that high fluorodeoxyglucose
uptake of the primary mass in high-risk stage II and stage III colon cancer does
not significantly correlate with DFS.
PMID- 28687026
TI - Urodynamics of men with urinary retention.
AB - OBJECTIVES: To describe the urodynamic characteristics of men with urinary
retention, and to show the diverse treatment plans based on urodynamic findings.
METHODS: We carried out a 3-year retrospective review of men with urinary
retention who were referred to our clinic for urodynamic evaluation. Men with a
history of neurogenic voiding dysfunction or major pelvic surgery were excluded.
Multichannel videourodynamic studies were carried out, and the subsequent
treatment modality offered was recorded. RESULTS: A total of 67 men with urinary
retention and a median age of 68 years underwent urodynamic evaluation. The
median maximum flow rate was 3 mL/s, and the median detrusor pressure at maximum
flow was 54 cm H2 O. Bladder outlet obstruction was diagnosed in 60%. Detrusor
underactivity was present in 73% according to the bladder contractility index;
however, just 29% were classified as having detrusor underactivity according to
isometric detrusor pressure, an alternative measure of contractility. A total of
76% of patients had low detrusor reserve (<20 cm H2 O). Based on urodynamic
findings, just 57% of patients were offered de-obstructive surgery. CONCLUSIONS:
In the present cohort, just 60% of men with urinary retention showed urodynamic
evidence of bladder outlet obstruction. Depending on how contractility is
measured (bladder contractility index vs isometric detrusor pressure), the rate
of detrusor underactivity varies. The majority of men with retention had a low
detrusor reserve. Given the wide spectrum of urodynamic findings in men with
retention, surgical intervention might not be necessary for all. Furthermore, a
careful consideration of urodynamics can assist in the selection of optimal
treatment.
PMID- 28687028
TI - Adjunctive use of chromoendoscopy may improve the diagnostic performance of
narrow-band imaging for small sessile serrated adenoma/polyp.
AB - BACKGROUND AND AIM: Endoscopic diagnosis of sessile serrated adenoma/polyp
(SSA/P) is challenging because of their subtle appearance. Narrow-band imaging
(NBI) is useful for diagnosis, but its utility with concurrent chromoendoscopy
(CE), especially to detect small SSA/P, is unproven. METHODS: This prospective
study enrolled 367 consecutive patients who underwent screening colonoscopy with
the finding of serrated polyps. Patients were divided into derivation and
validation cohorts: Diagnostic criteria using different endoscopic modalities
were generated by regression analysis in the derivation cohort and were validated
in the validation cohort for sensitivity, specificity, and accuracy. RESULTS:
There were 180 patients with 119 SSA/P and 147 hyperplastic polyps (HP) in the
derivation cohort and 187 patients with 177 SSA/P and 125 HP in the validation
cohort. With white-light endoscopy plus NBI, mucus cap, surface grooves, and
expanded crypt were most associated with SSA/P. With white-light endoscopy plus
CE, II-O pit pattern, mucus cap, and superficial telangiectasia were most
associated with SSA/P. With the combined use of these three modalities, II-O pit
pattern, mucus cap, and surface grooves were most associated with SSA/P. For
large serrated polyp, NBI in combination with CE had a better accuracy than NBI
alone (91% vs 86%, P = 0.025) to distinguish SSA/P from HP. CE alone had a better
accuracy than NBI alone for distinguishing small SSA/P from small HP (85% vs 72%,
P < 0.0001). CONCLUSION: Compared with NBI alone, adjunctive use of CE can
improve the diagnostic accuracy for distinguishing SSA/P from HP, especially for
small SSA/P.
PMID- 28687029
TI - Impact of metabolic syndrome on early recovery of continence after robot-assisted
radical prostatectomy.
AB - OBJECTIVES: To evaluate the impact of metabolic syndrome on the early recovery of
urinary continence after robot-assisted radical prostatectomy. METHODS: The
present study included a total of 302 consecutive Japanese patients with
clinically localized prostate cancer who underwent robot-assisted radical
prostatectomy. In this study, postoperative urinary continence was defined as no
leak or the use of a security pad. The continence status was assessed by
interviews before and 1 and 3 months after robot-assisted radical prostatectomy.
Metabolic syndrome was defined as follows: body mass index >=25 kg/m2 and two or
more of the following: hypertension, diabetes mellitus and dyslipidemia. The
effect of the presence of metabolic syndrome on the continence status of these
patients was retrospectively examined. RESULTS: A total of 116 (38.4%) and 203
(67.2%) of the 302 patients were continent at 1 and 3 months after robot-assisted
radical prostatectomy, respectively. A total of 31 (10.3%) patients were judged
to have metabolic syndrome. Despite the operative time being longer in patients
with metabolic syndrome, no significant differences were observed in the
remaining preoperative, intraoperative or postoperative variables between
patients with or without metabolic syndrome. On multivariate logistic regression
analysis, metabolic syndrome and the duration of hospitalization were
significantly correlated with the 1-month continence status. Similarly, metabolic
syndrome and estimated blood loss during surgery were independent predictors of
continence rates at 3 months after robot-assisted radical prostatectomy.
CONCLUSIONS: These findings suggest that the presence of metabolic syndrome could
have a significant impact on the early recovery of urinary continence after robot
assisted radical prostatectomy.
PMID- 28687027
TI - Emergency appendicectomy in Australia: findings from a multicentre, prospective
study.
AB - BACKGROUND: Emergency appendicectomy is the most common emergency surgical
procedure performed in Australia. Despite this frequency, there is a relative
paucity of contemporary, broad-based, local data that examine how emergency
appendicectomies are currently performed and what are the outcomes from these
operations. METHODS: A multicentre, prospective, observational study was
performed. Patients were recruited by local investigators for a period of 2
months with 30-day follow-up. Patients were eligible for study inclusion if they
underwent an emergency appendicectomy for suspected acute appendicitis. The
primary outcome of the study was the negative appendicectomy rate (NAR), with
secondary outcomes including 30-day complication rates, method of operation and
conversion rates. RESULTS: A total of 1189 patients were recruited across 27
centres. The NAR across all centres was 19.0%. 98.2% of appendicectomies were
performed with a laparoscopic-first approach. The rate of conversion from
laparoscopy to open operation was 2.4%. 9.4% of patients were recorded as having
one or more of the following complications: readmission (6.6%), surgical site
infection (1.9%), intra-abdominal abscess (2.7%) or further intervention (1.5%).
Patients who had an open operation had higher rates of readmission and surgical
site infection. CONCLUSION: The NAR found in this study is within the traditional
measures of acceptance; however, this rate is high when measured against modern
international benchmarks.
PMID- 28687031
TI - Electrochemical synthesis of Sm2O3 nanoparticles: Application in conductive
polymer composite films for supercapacitors.
AB - A novel electrosynthetic method was introduced to synthesize of Sm2O3
nanoparticles and furthermore, for improving the electrochemical performance of
conductive polymer, hybrid POAP/Sm2O3 films have then been fabricated by POAP
electropolymerization in the presence of Sm2O3 nanoparticles as active electrodes
for electrochemical supercapacitors. The structure, morphology, chemical
composition of Sm2O3 nanoparticles was examined. Surface and electrochemical
analyses have been used for characterization of Sm2O3 and POAP/Sm2O3 composite
films. Different electrochemical methods including galvanostatic charge discharge
experiments, cyclic voltammetry and electrochemical impedance spectroscopy have
been applied to study the system performance. The supercapacity behavior of the
composite film was attributed to the (i) high active surface area of the
composite, (ii) charge transfer along the polymer chain due to the conjugation
form of the polymer and finally (iii) synergism effect between conductive polymer
and Sm2O3 nanoparticles.
PMID- 28687030
TI - Photolysis of polycyclic aromatic hydrocarbons (PAHs) on Fe3+-montmorillonite
surface under visible light: Degradation kinetics, mechanism, and toxicity
assessments.
AB - Photochemical behavior of various polycyclic aromatic hydrocarbons (PAHs) on Fe3+
modified montmorillonite was explored to determine their potential kinetics,
pathways, and mechanism under visible light. Depending on the type of PAH
molecules, the transformation rate follows the order of benzo[a]pyrene ~
anthracene > benzo[a]anthracene > phenanthrene. Quantum simulation results
confirm the crucial role of "cation-pi" interaction between Fe3+ and PAHs on
their transformation kinetics. Primary intermediates, including quinones, ring
opening products and benzene derivatives, were identified by gas chromatography
mass spectrometer (GC-MS), and the possible photodegradation pathway of
benzo[a]pyrene was proposed. Meanwhile, radical intermediates, such as reactive
oxygen species (ROS) and free organic radicals, were detected by electron
paramagnetic resonance (EPR) technique. The photolysis of selected PAHs, such as
anthracene and benzo[a]pyrene, on clay surface firstly occurs by electron
transfer from PAHs to Fe3+-montmorillonite, followed by degradation involving
photo-induced ROS such as .OH and .O2-. To investigate the acute toxicity of
photolysis products, the Microtox(r) toxicity test was performed during the
photodegradation processes of various PAHs. As a result, the photo-irradiation
initially induces increased toxicity by generating reactive intermediates, such
as free organic radicals, and then the toxicity gradually decreases with
increasing of reaction time. Overall, the present study provides useful
information to understand the fate and photo-transformation of PAHs in
contaminated soils.
PMID- 28687032
TI - Granular tri-metal oxide adsorbent for fluoride uptake: Adsorption kinetic and
equilibrium studies.
AB - A novel adsorbent embedding Mg-Al-Zr mixed oxides with millimetre-sized calcium
alginate beads (SA-CMAZ) was synthesized, characterized, and applied for the
secondary removal of fluoride from wastewater. Key factors affecting the fluoride
adsorption, including initial fluoride concentration, contact time, initial pH
and coexisting anions, were investigated. The results showed that fluoride could
be removed by SA-CMAZ over a wide pH range, from 4 to 10. The presence of
coexisting anions weakened the adsorption of fluoride, and the decreasing order
of the removal towards fluoride was PO43->CO32->SO42->NO3-. The adsorption
follows a pseudo second order kinetic with theoretical adsorption capacity
(Qe,cal) and experimental adsorption capacity (Qe,exp) close to each other at the
temperatures of 303K, 308K, and 313K. The equilibrium data could be fitted by the
Freundlich isotherm model as the SA-CMAZ is a heterogeneous. The value of the
thermodynamic parameter indicated an endothermic adsorption process. A negative
value shows the feasibility and spontaneity of the material-anion interaction.
PMID- 28687033
TI - Propylsulfonic acid-anchored isocyanurate-based periodic mesoporous organosilica
(PMO-ICS-Pr-SO3H): A new and highly efficient recoverable nanoporous catalyst for
the one-pot synthesis of bis(indolyl)methane derivatives.
AB - A new propylsulfonic acid-anchored isocyanurate bridging periodic mesoporous
organosilica (PMO-ICS-Pr-SO3H) was prepared and shown to be a highly efficient
recyclable nanoporous catalyst for the one-pot synthesis of bis(indolyl)methane
derivatives in good to excellent yields from indole and different aldehydes in
EtOH under mild reaction conditions in short reaction times. Moreover, the
nanoporous catalyst was recovered and reused at least four times without
significant decrease in its catalytic activity. The PMO-ICS-Pr-SO3H catalyst was
characterizred by Fourier transform infrared (FTIR) spectroscopy,
thermogravimetry analysis (TGA) and N2 adsorption-desorption isotherms techniques
as well as field emission scanning electron microscopy (FESEM) and energy
dispersive X-ray (EDX) spectroscopy. Compared to the classical methodologies,
this method illustrated significant advantages including low loading of the
catalyst, high to excellent yields, short reaction times, avoiding the use of
toxic transition metals or reactive reagents for modification of the catalytic
activity, easy separation and purification of the products, and reusability of
the catalyst.
PMID- 28687034
TI - Adsorption and photophysical properties of fluorescent dyes over montmorillonite
and saponite modified by surfactant.
AB - In the present study, the adsorption capacities of two intercalated smectites,
CTAB-saponite and CTAB-montmorillonite with a cationic surfactant, were
investigated with three fluorescent dyes namely Rhodamine 640 perchlorate
rhodamine (Rho), sulforhodamine B (SR) and Kiton red 620 (KR). The adsorption
isotherms fit well with the non-linear Langmuir isotherm model and the maximum
adsorption capacities of all the composites are determined. The photophysical
properties such as anisotropy and fluorescence lifetime of all the fluorescent
dyes over the clay materials are determined. The set of experimental data based
on X-Ray diffraction (XRD), transmission electron microscopy (TEM), Thermal
analysis (TG-DTA) and fluorescence measurements allow highlighting the presence
or the absence of interactions between the dyes and the modified clay minerals.
PMID- 28687035
TI - Effect of Eudragit S100 nanoparticles and alginate chitosan encapsulation on the
viability of Lactobacillus acidophilus and Lactobacillus rhamnosus.
AB - In this study, we examined a novel method of microencapsulation with calcium
alginate-chitosan and Eudragit S100 nanoparticles for the improving viability of
probiotic bacteria, Lactobacillus acidophilus and Lactobacillus rhamnosus.
Extrusion technique was carried out in microencapsulation process. The viability
of two probiotics in single coated beads (with only chitosan), double coated
beads (with chitosan and Eudragit nanoparticles), and as free cells
(unencapsulated) were conducted in simulated gastric juice (pH 1.55, without
pepsin) followed by incubation in simulated intestinal juice (pH 7.5, with 1%
bile salt). In case of single coated beads, presumably, lack of sufficient
strength of chitosan under simulated gastric condition was the main reason of 4
log and 5-log reduction of the counts of the L. acidophilus and L. rhamnosus
respectively. The results showed that with the second coat forming (Eudragit
nanoparticles) over the first coat (chitosan), the strength of the beads and then
viability rate of the bacteria were increased in comparison with the single
coated beads.
PMID- 28687036
TI - Photosynthetic poly-beta-hydroxybutyrate accumulation in unicellular
cyanobacterium Synechocystis sp. PCC 6714.
AB - Poly-beta-hydroxybutyrate (PHB) production from CO2 has the potential to reduce
the production cost of this biodegradable polyesters, and also to make the
material more sustainable compared to utilization of sugar feedstocks. In this
study the unicellular cyanobacterium, Synechocystis sp. PCC 6714 has been
identified as an unexplored potential organism for production of PHB.
Synechocystis sp. PCC 6714 was studied under various cultivation conditions and
nutritional limitations. Combined effects of nitrogen and phosphorus deficiency
led to highest PHB accumulation under photoautotrophic conditions. Multivariate
experimental design and quantitative bioprocess development methodologies were
used to identify the key cultivation parameters for PHB accumulation. Biomass
growth and PHB accumulation were studied under controlled defined conditions in a
lab-scale photobioreactor. Specific growth rates were fourfold higher in
photobioreactor experiments when cultivation conditions were controlled. After 14
days of cultivation in nitrogen and phosphorus, limited media intracellular PHB
levels reached up to 16.4% from CO2. The highest volumetric production rate of
PHB was 59 +/- 6 mg L-1 day-1. Scanning electron microscopy of isolated PHB
granules of Synechocystis sp. PCC 6714 cultivated under nitrogen and phosphorus
limitations showed an average diameter of 0.7 um. The results of this study might
contribute towards a better understanding of photoautotrophic PHB production from
cyanobacteria.
PMID- 28687037
TI - Biodegradation and biodetoxification of Fusarium mycotoxins by Sphaerodes
mycoparasitica.
AB - A fungus Sphaerodes mycoparasitica SMCD 2220-01 is a host specific mycoparasite
against plant pathogenic Fusarium species. Fusarium spp. are producing a plethora
of mycotoxins including zearalenone (ZEN), deoxynivalenol (DON) and its
acetylated derivatives, 3-acetyl-deoxynivalenol (3-ADON) and 15-acetyl
deoxynivalenol (15-ADON). The SMCD 2220-01 strain substantially reduced DON, 3
ADON, 15-ADON, and ZEN production capacity in co-culture system. Degradation and
detoxification of the pure mycotoxins were also achieved when exposed to SMCD
2220-01 in shake flasks. The thin layer chromatography (TLC) combined with high
performance liquid chromatography-electrospray ionization-high resolution mass
spectrometry (HPLC-ESI-HRMS) revealed that the amount of mycotoxins exposed to
SMCD 2220-01 was considerably reduced compared to control. ZEN level was
decreased by 97%, while zearalenone sulfate ([M-H+SO3]- at m/z 397.1052
C18H21O8S1) was detected as a metabolite of ZEN converted to less toxic molecule
by the mycoparasite. Further, the mycoparasite appeared to degrade DON, 3-ADON,
and 15-ADON by 89, 58, and 72%, respectively. The deoxynivalenol sulfate ([M
COCH3+SO3-CH2O]- at m/z 345.2300 C14H17O8S1) was detected as a less toxic
metabolic product of DON and 3-ADON. These findings report the SMCD 2220-01
effectiveness to lower mycotoxins-producing capacities of Fusarium, degrade pure
mycotoxins and transform them to less toxic metabolites, opening new
opportunities for research and innovation for detoxification of mycotoxins.
PMID- 28687038
TI - Toward TiO2 Nanofluids-Part 2: Applications and Challenges.
AB - The research about nanofluids has been explosively increasing due to their
fascinating properties in heat or mass transportation, fluidity, and dispersion
stability for energy system applications (e.g., solar collectors, refrigeration,
heat pipes, and energy storage). This second part of the review summarizes recent
research on application of TiO2 nanofluids and identifies the challenges and
opportunities for the further exploration of TiO2 nanofluids. It is expected that
the two exhaustive reviews could be a helpful reference guide for researchers to
update the knowledge on research status of TiO2 nanofluids, and the critical
comments, challenges, and recommendations could be useful for future study
directions.
PMID- 28687039
TI - Carbon Nanodots as Dual-Mode Nanosensors for Selective Detection of Hydrogen
Peroxide.
AB - Hydrogen peroxide (H2O2) is an important product of oxidase-based enzymatic
reactions, such as glucose/glucose oxidase (GOD) reaction. Therefore, the probing
of generated H2O2 for achieving the detection of various carbohydrates and their
oxidases is very significative. Herein, we report one kind of dual-emission
carbon nanodots (CDs) that can serve as novel dual-mode nanosensors with both
fluorometric and colorimetric output for the selective detection of H2O2. The
dual-model nanosensors are established only by the undecorated dual-emission CDs,
where significant fluorometric and colorimetric changes are observed with the
addition of different concentrations of H2O2 in the CD solution, which benefit to
the achievement of the naked-eye detection for H2O2. The mechanism of the
nanosensors can be attributed to the fact that the external chemical stimuli like
hydroxyl radicals from H2O2 bring about the change of surface properties and the
aggregation of CDs, which dominate the emission and absorption of CDs. The
constructed dual-mode nanosensors exhibit good biocompatibility and high
selectivity toward H2O2 with a linear detection range spanning from 0.05 to 0.5 M
and allow the detection of H2O2 as low as 14 mM.
PMID- 28687040
TI - Miniaturized Stretchable and High-Rate Linear Supercapacitors.
AB - Linear stretchable supercapacitors have attracted much attention because they are
well suited to applications in the rapidly expanding field of wearable
electronics. However, poor conductivity of the electrode material, which limits
the transfer of electrons in the axial direction of the linear supercapacitors,
leads to a serious loss of capacity at high rates. To solve this problem, we use
gold nanoparticles to decorate aligned multiwall carbon nanotube to fabricate
stretchable linear electrodes. Furthermore, we have developed fine stretchable
linear supercapacitors, which exhibited an extremely high elasticity up to 400%
strain with a high capacitance of about 8.7 F g-1 at the discharge current of 1 A
g-1.
PMID- 28687041
TI - Enhanced Nonlinear Optical Effect in Hybrid Liquid Crystal Cells Based on
Photonic Crystal.
AB - Nonlinear-optical response of photorefractive hybrid liquid crystal (LC) cells
has been studied by means of dynamic holographic technique in two-wave mixing
arrangement. The LC cells include nonuniform silicon substrates comprising a
micrometer-range photonic crystal. A thin LC layer is set between silicon
substrate and a flat glass substrate covered by a transparent (ITO) electrode. A
dynamic diffraction grating was induced in the LC volume by the two-wave mixing
of laser beams with simultaneous application of DC electric field to the cell.
Theoretical model of Raman-Nath self-diffraction was developed. This model allows
for calculation of nonlinear optical characteristics in thin samples on the base
of two-wave mixing experimental data, and with taking into account light losses
on absorption and/or scattering. The hybrid LC cells demonstrate strong nonlinear
optical effect, prospective for many applications in electro-optical
microsystems, such as SLMs, as well as in multi-channel systems.
PMID- 28687043
TI - Swedish registries are promising but of limited value without validation.
PMID- 28687042
TI - Discovery of Heteroaromatic Sulfones As a New Class of Biologically Compatible
Thiol-Selective Reagents.
AB - The selective reaction of chemical reagents with reduced protein thiols is
critical to biological research. This reaction is utilized to prevent cross
linking of cysteine-containing peptides in common proteomics workflows and is
applied widely in discovery and targeted redox investigations of the mechanisms
underlying physiological and pathological processes. However, known and commonly
used thiol blocking reagents like iodoacetamide, N-ethylmaleimide, and others
were found to cross-react with oxidized protein sulfenic acids (-SOH) introducing
significant errors in studies employing these reagents. We have investigated and
are reporting here a new heteroaromatic alkylsulfone, 4-(5-methanesulfonyl
[1,2,3,4]tetrazol-1-yl)-phenol (MSTP), as a selective and highly reactive -SH
blocking reagent compatible with biological applications.
PMID- 28687044
TI - Dual-modified liposome codelivery of doxorubicin and vincristine improve
targeting and therapeutic efficacy of glioma.
AB - Therapeutic outcome for the treatment of glioma was often limited due to drug
resistance and low permeability of drug across the multiple physiological
barriers, including the blood-brain barrier (BBB), and the blood-tumor barrier
(BTB). In order to overcome these hurdles, we designed T7 and DA7R dual peptides
modified liposomes (abbreviated as T7/DA7R-LS) to efficiently co-delivery
doxorubicin (DOX) and vincristine (VCR) to glioma in this study. T7 is a seven
peptide ligand of transferrin receptors (TfR) capable of circumventing the BBB
and then targeting glioma. DA7R is a d-peptide ligand of vascular endothelial
growth factor receptor 2 (VEGFR 2) overexpressed on angiogenesis, presenting
excellent glioma-homing property. By combining the dual-targeting delivery
effect, the dual-modified liposomes displayed higher glioma localization than
that of single ligand-modified liposomes or free drug. After loading with DOX and
VCR, T7/DA7R-LS showed the most favorable antiglioma effect in vivo. In
conclusion, this dual-targeting, co-delivery strategy provides a potential method
for improving brain drug delivery and antiglioma treatment efficacy.
PMID- 28687045
TI - Sageretia thea (Osbeck.) modulated biosynthesis of NiO nanoparticles and their in
vitro pharmacognostic, antioxidant and cytotoxic potential.
AB - NiO nanoparticles are biosynthesized using Sageretia thea (Osbeck.) aqueous leave
extracts and their biological activities are reported. Nanoparticles (~18 nm)
were characterized through XRD, ATR-FTIR, EDS, SAED, HR-SEM/TEM and Raman
spectroscopy. Antibacterial activity was investigated against six pathogenic
bacterial strains (gram positive and gram negative) and their corresponding
minimum inhibitory concentrations (MICs) were calculated. UV-exposed
nanoparticles were investigated to have reduced MICs relative to the NiO
nanoparticles have not been exposed to UV. Moderate linear fungal growth
inhibition was observed while Mucor racemosus (percentage inhibition 64% +/-
2.30) was found to be most susceptible. Cytotoxicity was confirmed using brine
shrimps lethality assay (IC50 42.60 MUg/ml). MTT cytotoxicity was performed
against Leishmania tropica-KWH23 promastigotes and amastigotes revealed
significant percentage inhibition across the applied concentrations. IC50 values
were calculated as 24.13 MUg/ml and 26.74 MUg/ml for the promastigote and
amastigote cultures of Leishmania tropica. NiO nanoparticles were found.
Moderate, antioxidant potential was concluded through assays like DPPH, TAP and
TAC. Furthermore, protein kinase inhibition and alpha amylase inhibition is also
reported.
PMID- 28687046
TI - Formulation and in vitro/in vivo evaluation of chitosan-based film forming gel
containing ketoprofen.
AB - The film forming gel, adhered to skin surfaces upon application and formed a
film, has an advantage onto skin to provide protection and continuous drug
release to the application site. This study aimed to prepare a chitosan-based
film forming gel containing ketoprofen (CbFG) and to evaluate the CbFG and film
from CbFG (CbFG-film). CbFG were prepared with chitosan, lactic acid and various
skin permeation enhancers. The physicochemical characteristics were evaluated by
texture analysis, viscometry, SEM, DSC, XRD and FT-IR. To identify the mechanism
of skin permeation, in vitro skin permeation study was conducted with a Franz
diffusion cell and excised SD-rat and hairless mouse dorsal skin. In vivo
efficacy assessment in mono-iodoacetate (MIA)-induced rheumatoid arthritis animal
model was also conducted. CbFG was successfully prepared and, after applying CbFG
to the excised rat dorsal skin, the CbFG-film was also formed well. The
physicochemical characteristics of CbFG and CbFG-film could be explained by the
grafting of oleic acid onto chitosan in the absence of catalysts. In addition,
CbFG containing oleic acid had a higher skin permeation rate in comparison with
any other candidate enhancers. The in vivo efficacy study also confirmed
significant anti-inflammatory and analgesic effects. Consequently, we report the
successful preparation of chitosan-based film forming gel containing ketoprofen
with excellent mechanical properties, skin permeation and anti-inflammatory and
analgesic effects.
PMID- 28687048
TI - A core undergraduate curriculum in plastic surgery - a Delphi consensus study in
Scandinavia.
AB - BACKGROUND AND AIMS: In recent years, undergraduate medical education has
undergone a transition from a speciality-based to a more competence-based
training system. Consequently, whilst medical knowledge is rapidly expanding,
time for teaching of the surgical specialties is decreasing. Thus, there appears
to be a need to define the core competences that are to be taught. The aim of
this study was to establish a Scandinavian core undergraduate curriculum of
competences in plastic surgery, using scientific methods. METHODS: The Delphi
technique for group consensus was employed. An expert panel was recruited from
various plastic surgery subspecialties, institutions, and levels of clinical
experience, in four Nordic countries (Denmark, Finland, Norway and Sweden).
Questionnaires were sent out and answers collected electronically via Google
FormsTM. Following completion of three predefined rounds of anonymous
questionnaires; a final core curriculum competency list was agreed upon based on
a consensus agreement level of 80%. RESULTS: Two hundred and ninety-five
competences were suggested in the first round. In the second round, 76
competences (33 skills and 43 knowledge items) received a score >=3.00 on a 1-4
Likert scale. Final agreement in the third round resulted in a list of 68
competences with agreement above 80% (31 skills and 37 knowledge items).
CONCLUSIONS: This study proposes the first scientifically developed undergraduate
core curriculum in plastic surgery. It comprises of a consensus of competences a
recently graduated medical doctor should be expected to possess.
PMID- 28687047
TI - The role of irreversible electroporation (IRE) for locally advanced pancreatic
cancer: a systematic review of safety and efficacy.
AB - OBJECTIVES: Irreversible electroporation (IRE) is a new modality for tumor
ablation. Electrodes are placed around the tumor, and a pulsed, direct current
with a field strength of 2000 V/cm is delivered. The direct current drives cells
into apoptosis and cell death without causing significant heating of the tissues,
which spares the extracellular matrix and proteins. The purpose of this review
was to evaluate current experience of IRE for the ablation of pancreatic cancer.
MATERIAL AND METHODS: We searched PubMed for all studies of IRE in human
pancreatic cancer in English reporting at least 10 patients. RESULTS: The search
yielded 10 studies, comprising a total of 446 patients. Percutaneous IRE was done
in 142 patients, while 304 patients were treated during laparotomy. Tumor sizes
ranged from median 2.8 to 4.5 cm. Post-procedural complications occurred in 35%
of patients, most of them were less severe. Nine patients (2.0%) died after the
procedure. The technical success rate was 85-100%. The median recurrence-free
survival was 2.7-12.4 months after IRE treatment. The median overall survival was
7-23 months postoperatively. The longest overall survival was noted when IRE was
used in conjunction with pancreatic resection. CONCLUSIONS: IRE seems feasible
and safe with a low post-procedural mortality. Further efforts are needed to
address patient selection and efficacy of IRE, as well as the use of IRE for
'margin accentuation' during surgical resection.
PMID- 28687049
TI - A review of eleven cases of tuberculosis presenting as sternal wound abscess
after open heart surgery.
AB - BACKGROUND: Sternal wound infection with Mycobacterium tuberculosis is an
uncommon yet highly challenging disease that can be quite insidious with various
presentations. We hereby provide a review of 10 cases in current literature and
describe an additional case which illustrates the difficulties associated with
diagnosis. METHODS: We used PubMed and Google search engine to search the
literature for all published papers reporting on cases of sternal M. tuberculosis
infections post open-heart surgeries. RESULTS: A total of 11 cases were
presented, including a case of our own. The majority were males and were exposed
to endemic areas. The average age was 59.6 +/- 15.5 years. Coronary artery bypass
surgery accounted for 73% of procedures and the average time to symptoms onset
was 12.2 +/- 16.6 months. Diabetes was the most reported non-cardiac comorbidity.
Presenting symptoms varied and only 5 patients had other organs involved. Blood
tests and radiographic studies were neither sensitive nor specific. M.
tuberculosis culture on debrided tissues was the most sensitive test but often
forgotten initially. Diagnostic delay was seen in almost all cases, often leading
to unnecessary courses of antibiotics and aggressive surgical interventions.
Finally, all patients responded well to anti-tuberculosis treatment, with
reported treatment duration ranging from 9 to 12 months. CONCLUSION: M.
tuberculosis infection of the sternum should be suspected in late-onset sternal
wound infections post open-heart surgery especially when the course is chronic
and indolent.
PMID- 28687050
TI - Do women with fibromyalgia adhere to walking for exercise programs to improve
their health? Systematic review and meta-analysis.
AB - BACKGROUND: Walking is recommended for fibromyalgia, but the rate of adherence to
this exercise is not known. Poor adherence to physical exercise can limit the
effectiveness in health benefits. OBJECTIVES: To examine adherence to
interventions that include walking for fibromyalgia and to explore its moderators
among the characteristics of patients, of the walking prescription and of the
interventions. DATA SOURCES: References from 2000 to 2016 have been collected
through PubMed, PsycINFO, CINAHL, SPORTDiscus, Cochrane, and Teseo. STUDY
SELECTION: We included quasi-experimental and randomized controlled trials in
adults with fibromyalgia that involved walking for exercise. Two authors screened
records independently and disagreements were resolved by discussion. DATA
EXTRACTION: Independently extracted by two assessors. Methodological quality of
the studies was assessed using an ad hoc scale. DATA SYNTHESIS: Nineteen trials,
32 experimental groups, recruited a total of 983 participants (96.78% women) with
mean ages between 45 and 60.60. Adherence to the intervention program was
reported in 19 of 32 experimental groups and ranged, on average, from 73 to
87.20% depending on the type of assessment. Most relevant moderators of adherence
were the recruitment of participants through physicians and the nurses as
supervisors of exercise. CONCLUSION: Adherence rates (attendance at sessions) to
programs with walking were high. However, a lack of information precludes
knowledge of whether participants sustained walking between sessions or after the
treatment. Further work is required to examine in greater depth such contextual
variables of interventions as the professional-participant relationship or to
explore other possible moderators such as patient expectations of the treatment.
Implications for rehabilitation Adherence to walking programs is more likely if
doctors recommend the attendance at them. The combination with other activities
may result in better adherence to walking than those that are only-walking
exercise. The adherence to walking programs was larger in those in which nurses
supervised the exercise. It is necessary to have adherence as objective,
improving the record of adherence during treatment, assessing it between sessions
and with a follow-up after the end of treatment.
PMID- 28687051
TI - From experiments to ecosystems? Reviewing public participation, scientific
governance and the systemic turn.
AB - The article discusses a recent systemic turn in public participation in science
studies. It reviews the main lines of criticism brought forward in science,
technology and society towards public participation in science discourse and
argues that much of it refers to the field's preoccupation with isolated, stage
managed minipublics. It then discusses a series of efforts in science, technology
and society, and other fields to study public participation in a more systemic or
holistic perspective. The article advances the argument that there are different
ways of conceptualizing such a perspective, not all of which are well equipped to
account for contestation, conflict and power. We distinguish between an
aggregative approach, deliberative systems theory, an eco-systemic and a
decentred governance approach and argue that the latter allows us to study the
complexities of public participation without relying on a normative concept of
system and account for power relations that may structure the field of public
participation.
PMID- 28687052
TI - Borneol, a novel agent that improves central nervous system drug delivery by
enhancing blood-brain barrier permeability.
AB - The clinical application of central nervous system (CNS) drugs is limited by
their poor bioavailability due to the blood-brain barrier (BBB). Borneol is a
naturally occurring compound in a class of 'orifice-opening' agents often used
for resuscitative purposes in traditional Chinese medicine. A growing body of
evidence confirms that the 'orifice-opening' effect of borneol is principally
derived from opening the BBB. Borneol is therefore believed to be an effective
adjuvant that can improve drug delivery to the brain. The purpose of this paper
is to provide a comprehensive review of information accumulated over the past two
decades on borneol's chemical features, sources, toxic and kinetic profiles,
enhancing effects on BBB permeability and their putative mechanisms, improvements
in CNS drug delivery, and pharmaceutical forms. The BBB-opening effect of borneol
is a reversible physiological process characterized by rapid and transient
penetration of the BBB and highly specific brain regional distribution. Borneol
also protects the structural integrity of the BBB against pathological damage.
The enhancement of the BBB permeability is associated with the modulation of
multiple ATP-binding cassette transporters, including P-glycoprotein; tight
junction proteins; and predominant enhancement of vasodilatory neurotransmitters.
Systemic co-administration with borneol improves drug delivery to the brain in a
region-, dose- and time-dependent manner. Several pharmaceutical forms of borneol
have been developed to improve the kinetic and toxic profiles of co-administered
drugs and enhance their delivery to the brain. Borneol is a promising novel agent
that deserves further development as a BBB permeation enhancer for CNS drug
delivery.
PMID- 28687053
TI - Fabrication, in-vitro characterization, and enhanced in-vivo evaluation of
carbopol-based nanoemulsion gel of apigenin for UV-induced skin carcinoma.
AB - The aim of this study was to develop a potential novel formulation of carbopol
based nanoemulsion gel containing apigenin using tamarind gum emulsifier which
was having the smallest droplet size, the highest drug content, and a good
physical stability for Skin delivery. Apigenin loaded nanoemulsion was prepared
by high speed homogenization method and they were characterized with respect to
morphology, zeta potential, differential scanning calorimeter study, and
penetration studies. In-vitro release studies and skin permeation of apigenin
loaded nanoemulsion by goat abdominal skin was determined using Franz diffusion
cell and confocal laser scanning microscope (CLSM). The cytotoxicity of the
reported formulation was evaluated in HaCaT Cells (A) and A431 cells (B) by MTT
assay. The nanoemulsion formulation showed droplet size, polydispersity index,
and zeta potential of 183.31 nm, 0.532, and 31.9 mV, respectively. The
nanoemulsions were characterized by TEM demonstrated spherical droplets and FTIR
to ensure the compatibility among its ingredients. CLSM showed uniform
fluorescence intensity across the entire depth of skin in nanocarriers treatment,
indicating high penetrability of nanoemulsion gel through goatskin. The
nanoemulsion gel showed toxicity on melanoma (A341) in a concentration range of
0.4-2.0 mg/ml, but less toxicity toward HaCaT cells. The carbopol-based
nanoemulsion gel formulation of apigenin possesses better penetrability across
goatskin as compared to marketed formulation. Hence, the study postulates that
the novel nanoemulsion gel of apigenin can be proved fruitful for the treatment
of skin cancer in near future.
PMID- 28687054
TI - Enhancing cisplatin delivery to hepatocellular carcinoma HepG2 cells using dual
sensitive smart nanocomposite.
AB - Targeted entrance and accumulation of higher doses of drugs into malignant cells
could help in intensification of tumor specific cytotoxicity. A dual-responsive
nanogel, poly(N-isopropylacrylamide)-co-poly(N,N-(dimethylamino)ethyl
methacrylate) [P(NIPAM-co-DMA)] containing N-isopropylacrylamide (NIPAM) as
thermoresponsive monomer and N,N-(dimethylamino)ethyl methacrylate (DMA) as pH
responsive monomer and methylene-bis-acrylamide (MBA) as cross-linking agent, was
synthesized by free radical emulsion polymerization. Cisplatin along with
magnetic Fe3O4 nanoparticles (MNPs) was loaded into the nanogel by physically
embedding the magnetic nanoparticles into hydrogel matrix after gelation to
obtain drug-loaded magnetic nanocomposite [P(NIPAM-co-DMA)/Fe3O4]. Drug loading
efficiencies and drug release profiles of cisplatin-loaded P(NIPAM-co-DMA)
nanogel and P(NIPAM-co-DMA)/Fe3O4 nanocomposite were evaluated in vitro for
controlled drug delivery in different temperature and pH conditions. Finally, the
anticancer activity of P(NIPAM-co-DMA)/Fe3O4 nanocomposite on human liver HepG2
cells was evaluated. Nanogel and nanocomposite showed significantly higher (p <
.05) cisplatin release at 40 degrees C compared to 37 degrees C and at pH 5.7
compared to pH 7.4, demonstrating their temperature and pH sensitivity,
respectively. The cytotoxicity assay of drug free nanogel on HepG2 cell line
indicated that the nanogel is biocompatible and suitable as drug carrier.
Moreover, MTT assay revealed that the cisplatin-loaded nanocomposite represented
significant superior cytotoxicity (p < .05) to HepG2 cells as compared with free
cisplatin.
PMID- 28687055
TI - Psychometric properties of the Swedish version of the Falls Efficacy Scale
International for older adults with osteoporosis, self-reported balance deficits
and fear of falling.
AB - PURPOSE: Investigate the psychometric properties of the Swedish version of the
Falls Efficacy Scale-International (FES-I). METHOD: Cross-sectional study.
Community-dwelling older adults with self-reported balance deficits and fear of
falling were recruited from an ongoing randomised controlled study to evaluate
the psychometric properties of the FES-I using Rasch model analysis. RESULTS: The
Rasch model analysis revealed good category function, the questionnaire measured
one dimension with an explained variance of 68.6% and item goodness-of-fit with
mean square values (MnSq) 0.7-1.44. The item map showed that all items are spread
over the scale, which indicates different difficulties in the items. Non
satisfactory person goodness-of-fit was shown with seven persons and showed
person misfit according to both the MnSq-value and the z-value, 38 persons (40%)
showed a person misfit when only following the threshold for MnSq. CONCLUSIONS:
The Swedish version of FES-I shows good psychometric properties with
unidimensionality and item goodness-of-fit. Lower person goodness-of-fit was
shown probably because of confounding factors that may influence the answers. The
transformed values of the FES-I make it possible to use parametric statistics
preferable for this population in future research. Implications for
rehabilitation The Falls Efficacy Scale-International (FES-I) shows good
psychometric properties with unidimensionality, item goodness-of-fit and good
item reliability, which means that FES-I is a valuable tool when measuring
concerns about falling in an older population with osteoporosis and could be
useful in clinical settings. Confounding factors such as pain, high number of
falls, low fall self-efficacy, experience of previous falls, and vertigo may
influence the answers and result in low person goodness-of-fit.
PMID- 28687056
TI - The efficacy of treadmill training on balance dysfunction in individuals with
chronic stroke: a systematic review.
AB - BACKGROUND: Physical activity and exercise interventions are useful in
facilitating the functional recovery of those with chronic stroke and, routinely,
are gait-specific. While treadmill training has proven useful in gait performance
recovery post-stroke, its efficacy on balance dysfunction has not been
systematically reviewed. OBJECTIVES: The purpose of this systematic review was to
determine the effect of treadmill training (TT) interventions on balance
dysfunction in individuals with chronic stroke. METHODS: A systematic literature
search of PubMed, EMBASE, and CINAHL was performed. Eligible randomized
controlled trials were published between 2007 and 2016. Selected trials
investigated TT interventions in persons with chronic stroke and implemented at
least one objective balance measure. Methodological quality was assessed using
PEDro criteria. RESULTS: Eight studies met eligibility criteria and were included
in the qualitative analysis. Studies differed in TT implementation and use of
adjunctive treatments; however, all trials demonstrated improvements in balance
measures that were as effective, if not more so, than conventional physical
therapy treatments, including targeted balance training. CONCLUSIONS: This review
recognized moderate evidence in favor of TT interventions in balance and stroke
rehabilitation programs. With TT, intensity may be a more critical factor than
specificity and may offer additional carryover to recovery parameters of postural
control and balance, beyond gait performance. It is recommended that clinicians
utilizing TT incorporate objective measures of balance to assess the potential
for skill transference and improvements in balance. Higher quality studies and
additional research are needed to denote critical parameters by which
improvements in balance may be optimized.
PMID- 28687058
TI - The Participation Scale: psychometric properties of a South Indian translation
with hearing-impaired respondents.
AB - AIMS: The Participation Scale (P-Scale) is a widely used generic self-report
measure designed to assess an individual's participation restriction consequent
to any disease condition. The present study aimed to evaluate the validity and
reliability of a south Indian (Kannada language) version of the P-Scale for use
with adults with hearing loss. This study is a part of an ongoing research
program on the assessment of outcomes of hearing health rehabilitation with
hearing aids involving Indian client groups. METHODS: One hundred and three
adults with hearing loss completed the original English and the newly translated
adapted Kannada P-Scale questionnaire. Nearly half of the participants completed
repeat testing of the Kannada version 15 days after the initial assessment. Along
with the P-Scale, Kannada versions of the Hearing Handicap Questionnaire (HHQ)
and the Assessment of Quality of Life - 4 Dimensions Questionnaire (AQoL-4D) were
also administered. Based on predefined quality criteria, five different
psychometric properties of the P-Scale were evaluated, together with an analysis
of the Kannada P-Scale's factor structure. The psychometric properties assessed
included internal consistency, test-retest reliability, convergent validity,
discriminant validity, and floor-ceiling effects. RESULTS: Principal component
analysis indicated a four-factor complex structure, which explained 69.78% of the
variance in the Kannada P-Scale. High internal consistency (Cronbach's alpha =
0.90) and test-retest reliability (internal consistency coefficient >0.90) were
obtained. Comparisons with the HHQ (rho = 0.52) and AQoL-4 D (rho = 0.76)
indicated good convergent validity. Discriminant validity among the P-Scale
questions was acceptable (inter-item correlation <0.60). Floor and ceiling
effects were not evident in the Kannada P-Scale. CONCLUSIONS: The psychometric
characteristics of the Kannada P-scale were found to be sufficient for use with
the participant group (literate, Kannada-speaking adults with hearing loss) who
were assessed in this study. Further research is required to determine
generalizability of the Kannada P-Scale among other Kannada-speaking communities.
Implications for Rehabilitation The Kannada version of the Participation Scale (P
Scale) can be validly used with Kannada speaking adults with hearing loss. The
Kannada P-Scale can be used for clinical/research purposes to assess outcome
(specifically, change in participation restriction) before, during, and after the
hearing rehabilitation process. However, education and socioeconomic status may
have an effect of the Kannada P-Scale results and these factors need to be
further investigated prior to wider clinical use.
PMID- 28687057
TI - Factors influencing speech perception in noise for 5-year-old children using
hearing aids or cochlear implants.
AB - OBJECTIVE: We investigated the factors influencing speech perception in babble
for 5-year-old children with hearing loss who were using hearing aids (HAs) or
cochlear implants (CIs). DESIGN: Speech reception thresholds (SRTs) for 50%
correct identification were measured in two conditions - speech collocated with
babble, and speech with spatially separated babble. The difference in SRTs
between the two conditions give a measure of binaural unmasking, commonly known
as spatial release from masking (SRM). Multiple linear regression analyses were
conducted to examine the influence of a range of demographic factors on outcomes.
STUDY SAMPLE: Participants were 252 children enrolled in the Longitudinal
Outcomes of Children with Hearing Impairment (LOCHI) study. RESULTS: Children
using HAs or CIs required a better signal-to-noise ratio to achieve the same
level of performance as their normal-hearing peers but demonstrated SRM of a
similar magnitude. For children using HAs, speech perception was significantly
influenced by cognitive and language abilities. For children using CIs, age at CI
activation and language ability were significant predictors of speech perception
outcomes. CONCLUSIONS: Speech perception in children with hearing loss can be
enhanced by improving their language abilities. Early age at cochlear
implantation was also associated with better outcomes.
PMID- 28687059
TI - Exploring the interplay between autoimmunity and cancer to find the target
therapeutic hotspots.
AB - Autoimmunity arises when highly active immune responses are developed against the
tissues or substances of one's own body. It is one of the most prevalent
disorders among the old-age population with prospects increasing with age. The
major cause of autoimmunity and associated diseases is the dysregulation of host
immune surveillance. Impaired repairment of immune system and apoptosis
regulation can be seen as major landmarks in autoimmune disorders such as the
mutation of p53 gene which results in rheumatoid arthritis, bowel disease which
consequently lead to tissue destruction, inflammation and dysfunctioning of body
organs. Cytokines mediated apoptosis and proliferation of cells plays a
regulatory role in cell cycle and further in cancer development. Anti-TNF
therapy, Treg therapy and stem cell therapy have been used for autoimmune
diseases, however, with the increase in the use of immunomodulatory therapies and
their development for autoimmune diseases and cancer, the understanding of human
immune system tends to become an increasing requirement. Hence, the findings
associated with the relationship between autoimmune diseases and cancer may prove
to be beneficial for the improvement in the health of suffering patients. Here
in, we are eliciting the underlying mechanisms which result in autoimmune
disorders causing the onset of cancer, exploration of interactome to find the
pathways which are mutual to both, and recognition of hotspots which might play
important role in autoimmunity mediated therapeutics with different therapies
such as anti-TNF therapy, Treg therapy and stem cell therapy.
PMID- 28687060
TI - Safety limit warning levels for the avoidance of excessive sound amplification to
protect against further hearing loss.
AB - OBJECTIVE: To determine safe output sound pressure levels (SPL) for sound
amplification devices to preserve hearing sensitivity after usage. DESIGN: A
mathematical model consisting of the Modified Power Law (MPL) (Humes & Jesteadt,
1991 ) combined with equations for predicting temporary threshold shift (TTS) and
subsequent permanent threshold shift (PTS) (Macrae, 1994b ) was used to determine
safe output SPL. STUDY SAMPLE: The study involves no new human subject
measurements of loudness tolerance or threshold shifts. PTS was determined by the
MPL model for 234 audiograms and the SPL output recommended by four different
validated prescription recommendations for hearing aids. RESULTS: PTS can, on
rare occasion, occur as a result of SPL delivered by hearing aids at modern day
prescription recommendations. The trading relationship of safe output SPL,
decibel hearing level (dB HL) threshold, and PTS was captured with algebraic
expressions. Better hearing thresholds lowered the safe output SPL and higher
thresholds raised the safe output SPL. CONCLUSION: Safe output SPL can consider
the magnitude of unaided hearing loss. For devices not set to prescriptive
levels, limiting the output SPL below the safe levels identified should protect
against threshold worsening as a result of long-term usage.
PMID- 28687061
TI - A fatal and unusual iatrogenic fourth right lumbar artery injury complicating
wrong-level hemilaminectomy: a case report and literature review.
AB - The authors describe an unusual case of a fatal iatrogenic fourth lumbar artery
injury during left hemilaminectomy in a 38-year-old woman. At autopsy, gross
inspection revealed hemoperitoneum with 1,800 ml of free blood and massive
retroperitoneal extravasation. A laceration with irregular and jagged margins was
detected on the wall of the fourth right lumbar artery. The autopsy and the post
mortem TC investigations demonstrated that wrong-level hemilaminectomy was
performed for the herniated disc.
PMID- 28687062
TI - Evaluation of hand orthoses in Duchenne muscular dystrophy.
AB - PURPOSE: The purpose of this study was to evaluate whether treatment of boys with
Duchenne muscular dystrophy using hand orthoses could benefit joint mobility,
grip strength, or fine motor function. METHOD: Eight boys with Duchenne muscular
dystrophy were provided with individually customised rest orthoses. The results
were analysed using single-subject design. The study included a baseline and an
intervention phase. A follow-up examination was also performed. RESULTS: Boys
with less than 50 degrees passive wrist extension mobility were included. Wrist
extension of the dominant hand increased in four and was maintained in four.
Wrist extension in the non-dominant hand increased in five, was maintained in two
and decreased in one. Thumb abduction in the dominant hand increased in six and
two remained stable. In the non-dominant hand five increased and three remained
stable. Grip strength and fine motor function showed also positive results.
CONCLUSIONS: This study indicates that the use of hand orthoses in Duchenne
muscular dystrophy can delay development of contractures and improve passive
wrist extension and thumb abduction. Hand orthoses can therefore be recommended
for boys who start to develop contractures in the long finger flexors. Due to
small sample size further studies are needed to confirm this result. Implications
for rehabilitation Evaluation of hand orthoses in Duchenne muscular dystrophy.
Preserved hand function is of uttermost importance for performance of activities
in the late stages of Duchenne muscular dystrophy. Contractures of long finger
flexors affect hand function and limit performance of daily activities. Hand
orthoses can delay development of contractures and preserve hand function and
give prerequisites for independence. The occupational therapists should measure
wrist joint mobility regularly to be able to find the right time for intervention
with hand orthoses in this progressive disorder.
PMID- 28687063
TI - LGMD2E is the most common type of sarcoglycanopathies in the Iranian population.
AB - Sarcoglycanopathies (SGCs) which are caused by mutations in SGCA, SGCB, SGCG or
SGCD genes are a subgroup of autosomal-recessive limb-girdle-muscular-dystrophies
(LGMD2). Although frequencies of mutations in these genes are different among
populations, mutations in SGCA and SGCD, respectively, have the highest and
lowest frequencies in most populations. Here, we report the proportion of
mutations in SGC genes among a group of Iranian SGCs patients. Clinical features
and results of SGC genes screening of 25 SGCs probands are presented. Large
deletion mutations are confirmed with MLPA assays. In total, 15 candidate disease
causing mutations were observed in the SGCA, SGCB, SGCG and SGCD genes; ten were
novel. Fourteen (56%), seven (28%), three (12%) and one (4%) patient,
respectively, carried mutations in SGCB, SGCG, SGCD and SGCA. The findings
suggest that LGMD2E is the most common form of SGCs in the Iranian population and
that LGMD2D is the rarest. Twelve LGMD2E cases carried the same mutation. To the
best of knowledge, the mutation spectrum in SGCs is being reported for the first
time in Iranian population. The finding will be beneficial for screening and
genetic-counseling of SGCs patients in Iran.
PMID- 28687064
TI - Leachate generation from landfill in a semi-arid climate: A qualitative and
quantitative study from Sousse, Tunisia.
AB - Despite initiatives for enhanced recycling and waste utilization, landfill still
represents the dominant disposal path for municipal solid waste (MSW). The
environmental impacts of landfills depend on several factors, including waste
composition, technical barriers, landfill operation and climatic conditions. A
profound evaluation of all factors and their impact is necessary in order to
evaluate the environmental hazards emanating from landfills. The present paper
investigates a sanitary landfill located in a semi-arid climate (Tunisia) and
highlights major differences in quantitative and qualitative leachate
characteristics compared to landfills situated in moderate climates. Besides the
qualitative analysis of leachate samples, a quantitative analysis including the
simulation of leachate generation (using the HELP model) has been conducted. The
results of the analysis indicate a high load of salts (Cl, Na, inorganic
nitrogen) in the leachate compared to other landfills. Furthermore the
simulations with HELP model highlight that a major part of the leachate generated
originates form the water content of waste.
PMID- 28687065
TI - Second Language Perception of Mandarin Vowels and Tones.
AB - This study examines the discrimination of Mandarin vowels and tones by native
English speakers with varying amounts of Mandarin experience, aiming to
investigate the relative difficulty of these two types of sounds for English
speakers at different learning stages, and the source of their difficulty.
Seventeen advanced learners of Mandarin (Ex group), eighteen beginning learners
(InEx group), and eighteen English speakers naive to Mandarin (Naive group)
participated in an AXB discrimination task. The stimuli were two Mandarin vowel
contrasts, /li-ly/ and /lu-ly/, and two tonal contrasts, T1-T4 and T2-T3. The
predicted difficulty for each contrast was hypothesized based on the assimilation
of these sounds to English reported in previous work. The results showed that the
Naive group was more accurate with vowel contrasts than with tones, suggesting
that non-tonal language speakers without any Mandarin training are less sensitive
to tonal distinction than to vowels. The two learner groups, on the other hand,
were highly accurate with all contrasts except for the T2-T3 pair, and achieved
significantly higher accuracy than the Naive group on /li-ly/ and T1-T4. This
lends support to the view that experience in Mandarin improves English speakers'
sensitivity to tonal distinction, helping them discriminate some tones as
accurately as vowels. However, all three groups achieved low accuracy in
discriminating T2 and T3, suggesting that this contrast may be inherently
difficult and resistant to improvement. This study shows that various factors in
addition to the native language experience may affect the perception of non
native vowels and tones.
PMID- 28687066
TI - Genomic characterization of a large plasmid containing a bla NDM-1 gene carried
on Salmonella enterica serovar Indiana C629 isolate from China.
AB - BACKGROUND: The bla NDM-1 gene in Salmonella species is mostly reported in
clinical cases, but is rarely isolated from red and white meat in China. METHODS:
A Salmonella Indiana (S. Indiana) isolate was cultured from a chicken carcass
procured from a slaughterhouse in China. Antimicrobial susceptibility was tested
against a panel of agents. Whole-genome sequencing of the isolate was carried out
and data was analyzed. RESULTS: A large plasmid, denoted as plasmid pC629
(210,106 bp), containing a composite cassette, consisting of IS26-bla NDM-1-ble
MBL -?trpF-tat-cutA-ISCR1-sul1-qacE?1-aadA2-dfrA12-intI1-IS26 was identified. The
latter locus was physically linked with bla OXA-1, bla CTX-M-65, bla TEM-1
encoding genes. A mercury resistance operon merACDEPTR was also identified; it
was flanked on the proximal side, among IS26 element and the distally located on
the bla NDM-1 gene. Plasmid pC629 also contained 21 other antimicrobial
resistance-encoding genes, such as aac(6')-Ib-cr, aac(3)-VI, aadA5, aph(4)-Ia,
arr-3, blmS, brp, catB3, dfrA17, floR, fosA, mph(A), mphR, mrx, nimC/nimA, oqxA,
oqxB, oqxR, rmtB, sul1, sul2. Two virulence genes were also identified on plasmid
pC629. CONCLUSION: To the best of our knowledge, this is the first report of bla
NDM-1 gene being identified from a plasmid in a S. Indiana isolate cultured from
chicken carcass in China.
PMID- 28687068
TI - Erratum to: Serum albumin, a good indicator of persistent organ failure in acute
pancreatitis.
PMID- 28687067
TI - Genome-wide characterization of the aldehyde dehydrogenase gene superfamily in
soybean and its potential role in drought stress response.
AB - BACKGROUND: Aldehyde dehydrogenases (ALDHs) represent a group of enzymes that
detoxify aldehydes by facilitating their oxidation to carboxylic acids, and have
been shown to play roles in plant response to abiotic stresses. However, the
comprehensive analysis of ALDH superfamily in soybean (Glycine max) has been
limited. RESULTS: In present study, a total of 53 GmALDHs were identified in
soybean, and grouped into 10 ALDH families according to the ALDH Gene
Nomenclature Committee and phylogenetic analysis. These groupings were supported
by their gene structures and conserved motifs. Soybean ALDH superfamily expanded
mainly by whole genome duplication/segmental duplications. Gene network analysis
identified 1146 putative co-functional genes of 51 GmALDHs. Gene Ontology (GO)
enrichment analysis suggested the co-functional genes of these 51 GmALDHs were
enriched (FDR < 1e-3) in the process of lipid metabolism, photosynthesis, proline
catabolism, and small molecule catabolism. In addition, 22 co-functional genes of
GmALDHs are related to plant response to water deprivation/water transport.
GmALDHs exhibited various expression patterns in different soybean tissues. The
expression levels of 13 GmALDHs were significantly up-regulated and 14 down
regulated in response to water deficit. The occurrence frequencies of three
drought-responsive cis-elements (ABRE, CRT/DRE, and GTGCnTGC/G) were compared in
GmALDH genes that were up-, down-, or non-regulated by water deficit. Higher
frequency of these three cis-elements was observed for the group of up-regulated
GmALDH genes as compared to the group of down- or non- regulated GmALDHs by
drought stress, implying their potential roles in the regulation of soybean
response to drought stress. CONCLUSIONS: A total of 53 ALDH genes were identified
in soybean genome and their phylogenetic relationships and duplication patterns
were analyzed. The potential functions of GmALDHs were predicted by analyses of
their co-functional gene networks, gene expression profiles, and cis-regulatory
elements. Three GmALDH genes, including GmALDH3H2, GmALDH12A2 and GmALDH18B3,
were highly induced by drought stress in soybean leaves. Our study provides a
foundation for future investigations of GmALDH gene function in soybean.
PMID- 28687069
TI - gammadeltaTFH cells promote B cell maturation and antibody production in
neuroblastoma.
AB - BACKGROUND: Previous studies have shown that gammadelta TFH cells are capable of
modulating antibody production in immunized and infected mouse model. In recent
studies, human gammadelta TFH cells are shown to contribute to the activation of
humoral immunity and promote the maturation of B cells. However, little
information is available on their involvement in neuroblastoma (NB) pathogenesis.
RESULTS: In the present study, the frequency of gammadelta TFH cells in 74 NB
patients was significantly higher compared with that in 60 healthy controls.
Moreover, most gammadelta TFH cells in NB patients had a naive phenotype with up
regulation of CD25, CD69, HLA-DR and CD40L and down-regulation of ICOS.
Importantly, gammadelta TFH cells in NB patients produced more IL-4 and IL-10
than those in healthy controls. Furthermore, serum total IgG level was
significantly increased in NB patients compared with healthy controls. The
expression of CD23 on B cells was up-regulated while CD80 expression was
significantly down-regulated in NB patients. Further analysis of B cell
compartment showed that the frequency of CD19+CD27hi plasma cells was enhanced in
NB patients. Spearman's correlation analysis revealed that the frequency of
gammadelta TFH cells was positively correlated to serum total IgG level and
CD19+CD27hi plasma cells in NB patients, but negatively correlated to CD19+ B
cells. CONCLUSIONS: We concluded that gammadelta TFH cells might promote B cell
maturation and antibody production in NB patients.
PMID- 28687070
TI - Massively parallel nanowell-based single-cell gene expression profiling.
AB - BACKGROUND: Technological advances have enabled transcriptome characterization of
cell types at the single-cell level providing new biological insights. New
methods that enable simple yet high-throughput single-cell expression profiling
are highly desirable. RESULTS: Here we report a novel nanowell-based single-cell
RNA sequencing system, ICELL8, which enables processing of thousands of cells per
sample. The system employs a 5,184-nanowell-containing microchip to capture
~1,300 single cells and process them. Each nanowell contains preprinted
oligonucleotides encoding poly-d(T), a unique well barcode, and a unique
molecular identifier. The ICELL8 system uses imaging software to identify
nanowells containing viable single cells and only wells with single cells are
processed into sequencing libraries. Here, we report the performance and utility
of ICELL8 using samples of increasing complexity from cultured cells to mouse
solid tissue samples. Our assessment of the system to discriminate between mixed
human and mouse cells showed that ICELL8 has a low cell multiplet rate (< 3%) and
low cross-cell contamination. We characterized single-cell transcriptomes of more
than a thousand cultured human and mouse cells as well as 468 mouse pancreatic
islets cells. We were able to identify distinct cell types in pancreatic islets,
including alpha, beta, delta and gamma cells. CONCLUSIONS: Overall, ICELL8
provides efficient and cost-effective single-cell expression profiling of
thousands of cells, allowing researchers to decipher single-cell transcriptomes
within complex biological samples.
PMID- 28687071
TI - Recurrence of visceral and muco-cutaneous leishmaniasis in a patient under
immunosuppressive therapy.
AB - BACKGROUND: Leishmaniasis is a protozoan disease caused by parasites of the genus
Leishmania, transmitted to humans by sandflies. The diagnosis of leishmaniasis is
often challenging as it mimics many other infectious or malignant diseases. The
disease can present in three ways: cutaneous, mucocutaneous, or visceral
leishmaniasis, which rarely occur together or consecutively. CASE PRESENTATION:
The patient was a 52 years old immunosuppressed Belgian woman with a long history
of severe rheumatoid arthritis. She underwent bone marrow biopsy to explore
thrombocytopenia. Diagnosis of visceral leishmaniasis was made by identification
of Leishman Donovan (LD) bodies in macrophages. Treatment with liposomal
amphotericin B was successful. She later developed cutaneous leishmaniasis
treated with amphotericin B lipid complex. She next presented with relapsing
cutaneous lesions followed by rapidly progressing lymphadenopathies. Biopsy
confirmed the diagnosis of leishmaniasis. Treatments by miltefosine, amphotericin
B, N-methyl-glucamine antimoniate were subsequently initiated. She later
presented a recurrent bone marrow involvement treated with intramuscular
paromomycin and miltefosine. She died two years later from leukemia. At the time
of death, she presented with a mucosal destruction of the nose. A Leishmania
specific PCR (Polymerase Chain Reaction) identified L. infantum as etiological
agent. CONCLUSIONS: Clinicians should be aware of the potential concomitant or
sequential involvement of multiple anatomic localizations of Leishmania in
immunosuppressed patients.
PMID- 28687072
TI - Evaluating the feasibility of the KDIGO CKD referral recommendations.
AB - BACKGROUND: In 2012, the international nephrology organization Kidney Disease
Improving Global Outcomes (KDIGO) released recommendations for nephrology
referral for chronic kidney disease (CKD) patients. The feasibility of adhering
to these recommendations is unknown. METHODS: We conducted a retrospective
analysis of the primary care population at Brigham and Women's Hospital (BWH). We
translated referral recommendations based upon serum creatinine, estimated
glomerular filtration rate (eGFR), and albuminuria into a set of computable
criteria in order to project referral volume if the KDIGO referral
recommendations were to be implemented. Using electronic health record data, we
evaluated each patient using the computable criteria at the times that the
patient made clinic visits in 2013. We then compared the projected referral
volume with baseline nephrology clinic volume. RESULTS: Out of 56,461 primary
care patients at BWH, we identified 5593 (9.9%) who had CKD based on albuminuria
or estimated GFR. Referring patients identified by the computable criteria would
have resulted in 2240 additional referrals to nephrology. In 2013, this would
represent a 38.0% (2240/5892) increase in total nephrology patient volume and
67.3% (2240/3326) increase in new referral volume. CONCLUSIONS: This is the first
study to examine the projected impact of implementing the 2012 KDIGO referral
recommendations. Given the large increase in the number of referrals, this study
is suggestive that implementing the KDIGO referral guidelines may not be feasible
under current practice models due to a supply-demand mismatch. We need to
consider new strategies on how to deliver optimal care to CKD patients using the
available workforce in the U.S. health care system.
PMID- 28687073
TI - Association of neuron-specific enolase values with outcomes in cardiac arrest
survivors is dependent on the time of sample collection.
AB - BACKGROUND: Despite marked advances in intensive cardiology care, current options
for outcome prediction in cardiac arrest survivors remain significantly limited.
The aim of our study was, therefore, to compare the day-specific association of
neuron-specific enolase (NSE) with outcomes in out-of-hospital cardiac arrest
(OHCA) survivors treated with hypothermia. METHODS: Eligible patients were OHCA
survivors treated with targeted temperature management at 33 degrees C for 24 h
using an endovascular device. Blood samples for NSE levels measurement were drawn
on days 1, 2, 3, and 4 after hospital admission. Thirty-day neurological outcomes
according to the Cerebral Performance Category (CPC) scale and 12-month mortality
were evaluated as clinical end points. RESULTS: A total of 153 cardiac arrest
survivors (mean age 64.2 years) were enrolled in the present study. Using ROC
analysis, optimal cutoff values of NSE for prediction of CPC 3-5 score on
specific days were determined as: day 1 > 20.4 mcg/L (sensitivity 63.3%;
specificity 82.1%; P = 0.002); day 2 > 29.0 mcg/L (72.5%; 94.4%; P < 0.001); and
day 3 > 20.7 mcg/L (94.4%; 86.7%; P < 0.001). The highest predictive value,
however, was observed on day 4 > 19.4 mcg/L (93.5%; 91.0%; P < 0.001); NSE value
>50.2 mcg/L at day 4 was associated with poor outcome with 100% specificity and
42% sensitivity. Moreover, NSE levels measured on all individual days also
predicted 12-month mortality (P < 0.001); the highest predictive value for death
was observed on day 3 > 18.1 mcg/L (85.3%; 72.0%; P < 0.001). Significant
association with prognosis was found also for changes in NSE at different time
points. An NSE level on day 4 > 20.0 mcg/L, together with a change > 0.0 mcg/L
from day 3 to day 4, predicted poor outcome (CPC 3-5) with 100% specificity and
73% sensitivity. CONCLUSIONS: Our results suggest that NSE levels are a useful
tool for predicting 30-day neurological outcome and long-term mortality in OHCA
survivors treated with targeted temperature management at 33 degrees C. The
highest associations of NSE with outcomes were observed on day 4 and day 3 after
cardiac arrest.
PMID- 28687074
TI - Strength of functional signature correlates with effect size in autism.
AB - BACKGROUND: Disagreements over genetic signatures associated with disease have
been particularly prominent in the field of psychiatric genetics, creating a
sharp divide between disease burdens attributed to common and rare variation,
with study designs independently targeting each. Meta-analysis within each of
these study designs is routine, whether using raw data or summary statistics, but
combining results across study designs is atypical. However, tests of functional
convergence are used across all study designs, where candidate gene sets are
assessed for overlaps with previously known properties. This suggests one
possible avenue for combining not study data, but the functional conclusions that
they reach. METHOD: In this work, we test for functional convergence in autism
spectrum disorder (ASD) across different study types, and specifically whether
the degree to which a gene is implicated in autism is correlated with the degree
to which it drives functional convergence. Because different study designs are
distinguishable by their differences in effect size, this also provides a unified
means of incorporating the impact of study design into the analysis of
convergence. RESULTS: We detected remarkably significant positive trends in
aggregate (p < 2.2e-16) with 14 individually significant properties (false
discovery rate <0.01), many in areas researchers have targeted based on different
reasoning, such as the fragile X mental retardation protein (FMRP) interactor
enrichment (false discovery rate 0.003). We are also able to detect novel
technical effects and we see that network enrichment from protein-protein
interaction data is heavily confounded with study design, arising readily in
control data. CONCLUSIONS: We see a convergent functional signal for a subset of
known and novel functions in ASD from all sources of genetic variation. Meta
analytic approaches explicitly accounting for different study designs can be
adapted to other diseases to discover novel functional associations and increase
statistical power.
PMID- 28687075
TI - Seasonal influenza vaccination coverage and its determinants among nursing homes
personnel in western France.
AB - BACKGROUND: Influenza-associated deaths is an important risk for the elderly in
nursing homes (NHs) worldwide. Vaccination coverage among residents is high but
poorly effective due to immunosenescence. Hence, vaccination of personnel is an
efficient way to protect residents. Our objective was to quantify the seasonal
influenza vaccination (IV) coverage among NH for elderly workers and identify its
determinants in France. METHODS: We conducted a cross-sectional study in March
2016 in a randomized sample of NHs of the Ille-et-Vilaine department of Brittany,
in western France. A standardized questionnaire was administered to a randomized
sample of NH workers for face-to-face interviews. General data about the
establishment was also collected. RESULTS: Among the 33 NHs surveyed, IV coverage
for the 2015-2016 season among permanent workers was estimated at 20% (95%
Confidence Interval (CI) 15.3%-26.4%) ranging from 0% to 69% depending on the
establishments surveyed. Moreover, IV was associated with having previously
experienced a "severe" influenza episode in the past (Prevalence Ratio 1.48, 95%
CI 1.01-2.17), and varied by professional categories (p < 0.004) with better
coverage among administrative staff. Better knowledge about influenza prevention
tools was also correlated (p < 0.001) with a higher IV coverage. Individual
perceptions of vaccination benefits had a significant influence on the IV
coverage (p < 0.001). Although IV coverage did not reach a high rate, our study
showed that personnel considered themselves sufficiently informed about IV.
CONCLUSIONS: IV coverage remains low in the NH worker population in Ille-et
Vilaine and also possibly in France. Strong variations of IV coverage among NHs
suggest that management and working environment play an important role. To
overcome vaccine "hesitancy", specific communication tools may be required to be
adapted to the various NH professionals to improve influenza prevention.
PMID- 28687076
TI - Baccaurea angulata fruit juice reduces atherosclerotic lesions in diet-induced
Hypercholesterolemic rabbits.
AB - BACKGROUND: Atherosclerosis is the most common disease of large and medium-sized
arteries linked to oxidative stress, dyslipidemia as well as chronic
inflammation. The aim of this study was to evaluate the potential health benefits
of Baccaurea angulata (BA) fruit juice on the aorta of diet-induced
hypercholesterolemic rabbits, to detect an accumulation of fatty streak and
evaluate the percentage of atherosclerotic lesion accrued. METHODS: Thirty-five
healthy male adults New Zealand White rabbits were assigned to seven different
groups. Four groups were fed 1% cholesterol diet and 0, 0.5, 1.0, and 1.5 mL of
BA fruit juice per kg of rabbit daily (atherogenic groups), while the other three
groups were fed commercial rabbit pellet and 0, 0.5, and 1.0 mL of juice per kg
of rabbit daily (normocholesterolemic groups) for 90 days. The thoracic and
abdominal aorta between the heart origin and bifurcation into iliac arteries of
all the rabbits were carefully removed and analyzed accordingly. RESULTS: The
supplementation of the high-cholesterol diet of hypercholesterolemic rabbits with
only 0.5 mL BA/kg rabbit per day significantly (p < 0.001) improved aortic lipid
profile, attenuated aortic fatty streak development and reduced intima
thickening. Higher BA doses used (1.0 and 1.5 mL/kg rabbit per day) also
significantly (p < 0.001) decreased further the development of aortic fatty
streaks, reduced the thickening of the tunica intima layer and preserved
endothelial healing following arterial injury. CONCLUSION: Therefore, BA fruit is
a potential novel functional food with effective anti-inflammatory, anti
atherogenic and hypocholesterolemic activities.
PMID- 28687077
TI - Joint analysis of left ventricular expression and circulating plasma levels of
Omentin after myocardial ischemia.
AB - BACKGROUND: Omentin-1, also known as Intelectin-1 (ITLN1), is an adipokine with
plasma levels associated with diabetes, obesity, and coronary artery disease.
Recent studies suggest that ITLN1 can mitigate myocardial ischemic injury but the
expression of ITLN1 in the heart itself has not been well characterized. The
purpose of this study is to discern the relationship between the expression
pattern of ITLN1 RNA in the human heart and the level of circulating ITLN1
protein in plasma from the same patients following myocardial ischemia. METHODS:
A large cohort of patients (n = 140) undergoing elective cardiac surgery for
aortic valve replacement were enrolled in this study. Plasma and left ventricular
biopsy samples were taken at the beginning of cardiopulmonary bypass and after an
average of 82 min of ischemic cross clamp time. The localization of ITLN1 in
epicardial adipose tissue (EAT) was also further characterized with immunoassays
and cell fate transition studies. RESULTS: mRNA expression of ITLN1 decreases in
left ventricular tissue after acute ischemia in human patients (mean difference
280.48, p = 0.001) whereas plasma protein levels of ITLN1 increase (mean
difference 5.24, p < 0.001). Immunohistochemistry localized ITLN1 to the
mesothelium or visceral pericardium of EAT. Epithelial to mesenchymal transition
in mesothelial cells leads to a downregulation of ITLN1 expression. CONCLUSIONS:
Myocardial injury leads to a decrease in ITLN1 expression in the heart and a
corresponding increase in plasma levels. These changes may in part be due to an
epithelial to mesenchymal transition of the cells that express ITLN1 following
ischemia. Trial Registration Clinicaltrials.gov ID: NCT00985049.
PMID- 28687079
TI - Expression and function of phosphodiesterases (PDEs) in the rat urinary bladder.
AB - BACKGROUND: It has been shown that hosphodiesterases (PDEs) play an important
role in mediating the smooth muscle tone of rat urinary bladder. However, the
gene expression profiles of them were still unknown. METHODS: Urinary bladder
Strips were obtained from both neonatal and adult Sprague-Dawley rats. RT
PCR/western blot and organ bath were used to measure the expression and function
of PDEs. RESULTS: Adult rat urinary bladder expressed various PDE mRNA with the
following rank order: PDE5A ~ PDE9A ~ PDE10A > PDE2A ~ PDE4A ~ PDE4D > PDE4B ~
PDE3B ~ PDE8B ~ PDE7A ~ PDE7B > PDE1A. PDE1B, PDE1C, PDE3A, PDE4C, PDE8A, and
PDE11A were not detected. Of interest, the mRNA and protein of PDE3A were
significantly decreased in adult rat urinary bladder compared to neonatal rat
urinary bladder. Cilostamide, a specific inhibitor for PDE3, significantly
inhibited the amplitude and frequency of carbachol-enhanced phasic contractions
of neonatal rat bladder strips by 38.8% and 12.1%, respectively. Compared to the
neonatal rat bladder, the effect of cilostamide was significantly blunted in
adult rat urinary bladder: the amplitude and frequency of carbachol-enhanced
phasic contractions were decreased by 13.4% (P < 0.01 vs neonatal rat bladder)
and 4.4%, respectively. However, the mRNA and the protein levels of PDE3B were
similar between neonatal and adult rat bladder. CONCLUSION: We found that several
PDE isoforms were expressed in the rat urinary bladder with distinct levels.
Moreover, we showed that the function of PDE3 was blunted in adult rat bladder
likely due to the decreased expression of PDE3A.
PMID- 28687078
TI - Prolonged and high dosage of tigecycline - successful treatment of
spondylodiscitis caused by multidrug-resistant Acinetobacter baumannii: a case
report.
AB - BACKGROUND: The incidence of infectious spondylodiscitis has been increasing over
the last few years. This reflects the expanding elderly and immunocompromised
populations and the rising implementation of invasive spinal procedures.
Infection may be inoculated into the disc space directly during invasive spinal
procedures. Osteomyelitis caused by Acinetobacter species is rare and mainly
caused by multidrug-resistant strains. CASE PRESENTATION: We present the case of
a 72-year-old Greek woman with postoperative spondylodiscitis caused by a
multidrug-resistant Acinetobacter baumannii strain that was successfully treated,
after she declined surgical treatment, with prolonged and high dosage of
tigecycline. She received intravenously administered tigecycline 200 mg per day
for 60 days and then 100 mg per day for a total of 102 days and was infection
free. CONCLUSIONS: We reviewed the literature on the role of Acinetobacter
baumannii as a cause of osteomyelitis, emphasizing the difficulty of treatment
and the potential role of tigecycline in conservative treatment of the infection.
We believe that 102 days in total is the longest time that any patient has
received tigecycline in the literature, thus our patient is a unique case of
successful treatment of spondylodiscitis.
PMID- 28687080
TI - Inhibition of RNA polymerase II allows controlled mobilisation of
retrotransposons for plant breeding.
AB - BACKGROUND: Retrotransposons play a central role in plant evolution and could be
a powerful endogenous source of genetic and epigenetic variability for crop
breeding. To ensure genome integrity several silencing mechanisms have evolved to
repress retrotransposon mobility. Even though retrotransposons fully depend on
transcriptional activity of the host RNA polymerase II (Pol II) for their
mobility, it was so far unclear whether Pol II is directly involved in repressing
their activity. RESULTS: Here we show that plants defective in Pol II activity
lose DNA methylation at repeat sequences and produce more extrachromosomal
retrotransposon DNA upon stress in Arabidopsis and rice. We demonstrate that
combined inhibition of both DNA methylation and Pol II activity leads to a strong
stress-dependent mobilization of the heat responsive ONSEN retrotransposon in
Arabidopsis seedlings. The progenies of these treated plants contain up to 75 new
ONSEN insertions in their genome which are stably inherited over three
generations of selfing. Repeated application of heat stress in progeny plants
containing increased numbers of ONSEN copies does not result in increased
activation of this transposon compared to control lines. Progenies with
additional ONSEN copies show a broad panel of environment-dependent phenotypic
diversity. CONCLUSIONS: We demonstrate that Pol II acts at the root of transposon
silencing. This is important because it suggests that Pol II can regulate the
speed of plant evolution by fine-tuning the amplitude of transposon mobility. Our
findings show that it is now possible to study induced transposon bursts in
plants and unlock their use to induce epigenetic and genetic diversity for crop
breeding.
PMID- 28687081
TI - Potential Mediators between Fibromyalgia and C-Reactive protein: Results from a
Large U.S. Community Survey.
AB - BACKGROUND: Fibromyalgia, a potentially debilitating chronic pain syndrome of
unknown etiology, may be characterized by inflammation. In this study, we
investigated the relation of FMS to serum C-reactive protein (CRP) in a large
population of adults (18+) and investigated the influence of other factors on
this relationship, including BMI, comorbidities, as well as mood and sleep
disturbance. METHODS: Participants were 52,535 Ohio Valley residents
(Fibromyalgia n = 1125). All participants completed a comprehensive health survey
(2005-2006) part of the C8 Health Project; serum levels of CRP were obtained, as
was history of Fibromyalgia physician diagnosis. Logistic and linear regressions
were used for this cross-sectional analysis. RESULTS: Mean CRP was higher among
participants reporting Fibromyalgia than those without (5.54 +/- 9.8 vs.3.75 +/-
7.2 mg/L, p < .0001)). CRP level showed a strong, positive association with FMS
(unadjusted odds ratio (OR) for highest vs. lowest quartile = 2.5 (CI 2.1,3.0;p
for trend < .0001)); adjustment for demographic and lifestyle factors attenuated
but did not eliminate this association (AOR for highest vs. lowest quartile = 1.4
(CI 1.1,1.6;p for trend < .0001)). Further addition of body mass index (BMI) and
comorbidities to the model markedly weakened this relationship (AORs,
respectively, for highest vs lowest CRP quartile = 1.2 (CI 1.0,1.4) and 1.1 (CI
0.9,1.3). In contrast, inclusion of mood and sleep impairment only modestly
reduced the adjusted risk estimate (AORs for highest vs. lowest quartile = 1.3
(CI 1.1,1.5) for each)). CONCLUSIONS: Findings from this large cross-sectional
study indicate a significant positive cross-sectional association of Fibromyalgia
to serum C-reactive protein may be explained, in part, by BMI and comorbidity.
Prospective research is needed to confirm this, and clarify the potential
mediating influence of obesity and comorbid conditions on this relationship.
PMID- 28687083
TI - Erratum to: Effectiveness of a novel mobile health education intervention (Peek)
on spectacle wear among children in India: study protocol for a randomized
controlled trial.
PMID- 28687082
TI - Experiences of inequitable care among Afghan mothers surviving near-miss
morbidity in Tehran, Iran: a qualitative interview study.
AB - BACKGROUND: Providing equitable maternal care to migrants is a seriously
challenging task for hosting countries. Iran, the second-most accessed country
for refugees from Afghanistan, has achieved maternal health improvement. However,
Afghan women with near-miss morbidity faced pre-hospital delays and disparity in
maternal care at hospitals. This study explores experiences of maternal care
among Afghan women surviving near-miss morbidity to increase insight into
healthcare improvements for migrants. METHODS: A qualitative study was conducted
at university hospitals in Tehran, from April 2013 to May 2014. A total of 11
Afghan women and 4 husbands were interviewed when women recovered from near-miss
morbidity that occurred around the childbirth period. Mothers were identified
prospectively using the WHO maternal near-miss approach. Thematic analysis was
used along with a data-driven approach to organize data guided by the 'three
delays model' theoretical framework. RESULTS: Mistreatment in the form of
discrimination and insufficient medical attention were key experiences.
Participants commonly perceived poor women-professional communication and delays
in recognizing obstetric complications despite repeated care-seeking. Financial
constraints, costly care, lack of health insurance, and low literacy were
experienced barriers to accessing care to a lesser extent. Non-somatic
consequences of near-miss morbidity affected mothers and families for extended
periods. CONCLUSIONS: Near-miss survivors' experiences provided remarkable
insights into maternal care of Afghans in Iran. The challenge for the health
system and professionals is to provide equitable care with dignity and improve
communication skills with caring attitudes toward ethnic minorities. Antenatal
visits provide the best and most appropriate opportunities to tackle health
illiteracy in Afghan women.
PMID- 28687084
TI - How to remove the grey area between ventilator-associated pneumonia and
ventilator-associated tracheobronchitis?
PMID- 28687085
TI - Regulation of early growth response 2 expression by secreted frizzled related
protein 1.
AB - BACKGROUND: Secreted frizzled-related protein 1 (SFRP1) expression is down
regulated in a multitude of cancers, including breast cancer. Loss of Sfrp1 also
exacerbates weight gain as well as inflammation. Additionally, loss of SFRP1
enhances TGF-beta signaling and the downstream MAPK pathway. TGF-beta has been
shown to increase the expression of Early Growth Response 2 (EGR2), a
transcription factor implicated in immune function in a wide variety of cell
types. The work described here was initiated to determine whether SFRP1
modulation affects TGF-beta mediated EGR2 expression in mammary tissues as well
as macrophage polarization. METHODS: Real-time PCR analysis was performed to
examine EGR2 expression in human and murine mammary epithelial cells and tissues
in response to SFRP1 modulation. Chemical inhibition was employed to investigate
the roles TGF-beta and MAPK signaling play in the control of EGR2 expression in
response to SFRP1 loss. Primary murine macrophages were isolated from Sfrp1-/-
mice and stimulated to become either M1 or M2 macrophages, treated with
recombinant SFRP1, and real-time PCR was used to measure the expression of murine
specific M1/M2 markers [Egr2 (M2) and Gpr18 (M1)]. Immunohistochemical analysis
was used to measure the expression of human specific M1/M2 markers [CD163 (M2)
and HLA-DRA (M2)] in response to rSFRP1 treatment in human mammary explant
tissue. RESULTS: Knockdown of SFRP1 expression increases the expression of EGR2
mRNA in human mammary epithelial cells and addition of rSFRP1 decreases the
expression of EGR2 when added to explant mammary gland tissues. Chemical
inhibition of both TGF-beta and MAPK signaling in Sfrp1-/- or knockdown mammary
epithelial cells results in decreased expression of EGR2. Stimulated murine
macrophages obtained from Sfrp1-/- mice and treated with rSFRP1 exhibit a
reduction in Egr2 expression and an increase in Gpr18 mRNA expression. Human
mammary explant tissue treated with rSFRP1 decreases CD163 protein expression
whereas there was no effect on the expression of HLA-DRA. CONCLUSIONS: Loss of
SFRP1 likely contributes to tumor progression by altering the expression of a
critical transcription factor in both the epithelium and the immune system.
PMID- 28687087
TI - A rare case of malignant solitary fibrous tumor in prostate with review of the
literature.
AB - BACKGROUND: Solitary fibrous tumor is an uncommon soft tissue neoplasm with
intermediate biological behavior, which rarely metastasizes. Malignant solitary
fibrous tumor, although not clearly defined, is rarely described in the prostate.
The present case is characterized by some peculiarities if compared with
previously reported cases of prostatic malignant solitary fibrous tumor. Firstly,
it does not show a homogeneous morphology: part of the neoplasm (about 50%)
showed the features of a conventional solitary fibrous tumor, while the remaining
part showed the features of a malignant solitary fibrous tumor. In addition, the
case is the first malignant solitary fibrous tumor reaching a huge diameter of 20
cm and replacing all prostatic parenchyma. Interestingly, normal prostatic
parenchyma was observed on left-lobe trans-rectal needle-core biopsies, but was
totally absent in surgical specimen. Since radical prostatectomy was carried out
about 4 months after the biopsies, such discordant data may suggest exceedingly
rapid growth of the neoplasm. CASE PRESENTATION: We report a case of a 62-year
old male, presented at medical observation for urinary retention, constipation
and an enlarged prostate gland. A trans-rectal prostatic biopsy showed a low
grade spindle cell neoplasm. Histopathological examination of the prostatectomy
specimen showed patternless architecture with hypocellular and hypercellular
areas and hemangiopericytoma-like vessels. In some fields the neoplasm was
characterized by a high mitotic index and evident cellular atypia.
Immunohistochemically, neoplastic cells were positive for CD34, bcl2, CD99, STAT6
and partially for PgR. The neoplasm was diagnosed as a malignant solitary fibrous
tumor. CONCLUSIONS: The differential diagnosis of spindle cells tumors arising in
the prostrate is broad and includes lesions of epithelial and mesenchymal origin,
primary prostatic lesions such as stromal tumors of uncertain malignant potential
and stromal sarcoma, as well as anatomically ubiquitous soft tissue neoplasms.
Solitary fibrous tumors should be considered in cases of prostatic tumors with a
spindled morphology, but malignancy in such tumors is extremely rare in the
prostate. A review of literature showed only four additional cases. Because of
the unpredictable biological behavior and the possibility of recurrence, a long
term clinical and instrumental follow-up is recommended.
PMID- 28687088
TI - Canonical mRNA is the exception, rather than the rule.
AB - A report on the Second Aegean International Conference on the Long and the Short
of Non-Coding RNAs, held in Heraklion, Greece, 9-14 June 2017.
PMID- 28687086
TI - Ivermectin susceptibility and sporontocidal effect in Greater Mekong Subregion
Anopheles.
AB - BACKGROUND: Novel vector control methods that can directly target outdoor malaria
transmission are urgently needed in the Greater Mekong Subregion (GMS) to
accelerate malaria elimination and artemisinin resistance containment efforts.
Ivermectin mass drug administration (MDA) to humans has been shown to effectively
kill wild Anopheles and suppress malaria transmission in West Africa. Preliminary
laboratory investigations were performed to determine ivermectin susceptibility
and sporontocidal effect in GMS Anopheles malaria vectors coupled with
pharmacokinetic models of ivermectin at escalating doses. METHODS: A population
based pharmacokinetic model of ivermectin was developed using pre-existing data
from a clinical trial conducted in Thai volunteers at the 200 ug/kg dose. To
assess ivermectin susceptibility, various concentrations of ivermectin compound
were mixed in human blood meals and blood-fed to Anopheles dirus, Anopheles
minimus, Anopheles sawadwongporni, and Anopheles campestris. Mosquito survival
was monitored daily for 7 days and a non-linear mixed effects model with probit
analyses was used to calculate concentrations of ivermectin that killed 50%
(LC50) of mosquitoes for each species. Blood samples were collected from
Plasmodium vivax positive patients and offered to mosquitoes with or without
ivermectin at the ivermectin LC25 or LC5 for An. dirus and An. minimus. RESULTS:
The GMS Anopheles displayed a range of susceptibility to ivermectin with species
listed from most to least susceptible being An. minimus (LC50 = 16.3 ng/ml) > An.
campestris (LC50 = 26.4 ng/ml) = An. sawadwongporni (LC50 = 26.9 ng/ml) > An.
dirus (LC50 = 55.6 ng/ml). Mosquito survivorship results, the pharmacokinetic
model, and extensive safety data indicated that ivermectin 400 ug/kg is the ideal
minimal dose for MDA in the GMS for malaria parasite transmission control.
Ivermectin compound was sporontocidal to P. vivax in both An. dirus and An.
minimus at the LC25 and LC5 concentrations. CONCLUSIONS: Ivermectin is lethal to
dominant GMS Anopheles malaria vectors and inhibits sporogony of P. vivax at safe
human relevant concentrations. The data suggest that ivermectin MDA has potential
in the GMS as a vector and transmission blocking control tool to aid malaria
elimination efforts.
PMID- 28687089
TI - It's all about the money? A qualitative study of healthcare worker motivation in
urban China.
AB - BACKGROUND: China's healthcare reform programme continues to receive much
attention. Central to these discussions has been how the various financial
incentives underpinning reform efforts are negatively impacting on the healthcare
workforce. Research continues to document these trends, however, qualitative
analysis of how these incentives impact on the motivation of healthcare workers
remains underdeveloped. Furthermore, the application of motivational theories to
make sense of healthcare worker experiences has yet to be undertaken. METHODS:
The purpose of our paper is to present a comparative case study account of
healthcare worker motivation across urban China. It draws on semi structured
interviews (n = 89) with a range of staff and organisations across three
provinces. In doing so, the paper analyses how healthcare worker motivation is
influenced by a variety of financial incentives; how motivation is influenced by
the opportunities for career development; and how motivation is influenced by the
day to day pressures of meeting patient expectations. RESULTS: The experience of
healthcare workers in China highlights how a reliance on financial incentives has
challenged their ability to maintain the values and ethos of public service. Our
findings suggest greater attention needs to be paid to the motivating factors of
improved income and career development. Further work is also needed to nurture
and develop the motivation of healthcare workers through the building of trust
between fellow workers, patients, and the public. CONCLUSIONS: Through the
analysis of healthcare worker motivation, our paper presents a number of ways
China can improve its current healthcare reform efforts. It draws on the
experience of other countries in calling for policy makers to support alternative
approaches to healthcare reform that build on multiple channels of motivation to
support healthcare workers.
PMID- 28687091
TI - Routine Orthopedic Evaluation in Foals.
AB - In order to recognize abnormalities on the physical evaluation, it is mandatory
to understand normal developmental variations of the musculoskeletal system. Many
abnormalities are self-limiting and, therefore, it is important to recognize
which problems require intervention for a successful outcome and which may be
complicated by treatment. The importance of a complete and thorough physical
evaluation cannot be overemphasized and is the most productive diagnostic tool
for recognizing most abnormalities of the skeletal system whether as a component
of an after-foaling examination or for lameness or conformation evaluation in
foals of all ages.
PMID- 28687090
TI - The effects of the location of cancer stem cell marker CD133 on the prognosis of
hepatocellular carcinoma patients.
AB - BACKGROUND: CD133 (prominin-1) is widely believed to be a cancer stem cell marker
in various solid tumor types, and CD133 has been correlated with tumor-initiating
capacity. Recently, the nuclear location of CD133 expression in tumors has been
discussed, but hepatocellular carcinoma (HCC) has not been included in these
discussions. The goal of this study was to investigate the location of CD133
expression in HCC and this location's potential value as a prognostic indicator
of survival in patients with HCC. METHODS: We enrolled 119 cancerous tissues and
pair-matched adjacent normal liver tissue from HCC patients. These tissues were
obtained immediately after operation, and tissue microarrays were subsequently
constructed. The expression of CD133 was measured by immunohistochemistry (IHC),
and the correlations between this expression and clinical characteristics and
prognosis was estimated using statistical analysis. RESULTS: The results showed
that the CD133 protein expression levels of HCC in both the cytoplasm and nucleus
were significantly higher than adjacent normal liver tissue. Kaplan-Meier
survival and Cox regression analyses revealed that high CD133 expression in the
cytoplasm was an independent predictor of poor prognosis for the overall survival
(OS) and relapse-free survival (RFS) rates of HCC patients (P = 0.028 and P =
0.046, respectively). Surprisingly, high nuclear CD133 expression of HCC was an
independent predictor of the good prognosis of the OS and RFS rates of HCC
patients (P = 0.023 and P = 0.012, respectively). CONCLUSIONS: The clinical
evidence that revealed cytoplasmic CD133 expression was correlated with poor
prognosis, while nuclear CD133 expression was significantly correlated with
favorable prognosis.
PMID- 28687092
TI - Septic Arthritis, Physitis, and Osteomyelitis in Foals.
AB - Despite differences in etiology and diagnostics, the mainstay of therapy in the
foal is similar to the adult: local lavage and/or debridement and local
antimicrobial therapy. When musculoskeletal infection is concurrent with neonatal
sepsis, the prognosis for survival is fair. When musculoskeletal infection is the
primary problem, the prognosis is fair to good for survival of synovial, bony,
and physeal infections with appropriate and aggressive local therapy. Recent
literature may indicate that prognosis for survival and potential athleticism in
foals that are treated expediently with local therapies and are without
comorbidities may be more favorable than has been previously indicated.
PMID- 28687093
TI - Flexural Deformity of the Distal Interphalangeal Joint.
AB - Flexural deformities in young horses are commonly referred to as contracted
tendons, which is a term that is not consistent with what is currently understood
about their cause. Flexural deformity of the distal interphalangeal joint can be
either congenital (present at birth) or acquired (develop at a later stage of
growth typically between 1 and 6 months of age). These 2 manifestations are
commonly managed differently depending on the cause, age of onset, severity,
duration, complicating factors, and owner expectations. Early recognition and
appropriate intervention are essential to ensure that it is not performance
limiting.
PMID- 28687094
TI - Angular Limb Deformities: Growth Augmentation.
AB - Angular limb deformities are seen in young foals and are defined as lateral or
medial deviations of the limb in the frontal plane distal to a particular joint.
Several factors can contribute to the development of an angular limb deformity.
Early assessment of the level of ossification of the cuboidal bones is critical
to avoid complications long term. Although most deviations self-correct with
minimal intervention other than modifications in exercise and hoof trimming, some
require surgical intervention in the form of growth acceleration or retardation.
This article focuses on growth augmentation techniques, such as
hemicircumferential transection and elevation.
PMID- 28687095
TI - Angular Limb Deformities: Growth Retardation.
AB - Angular limb deformities are common in foals; however, the importance of the
deformity and if treatment is required depend on the degree of deformity relative
to normal conformation for stage of growth, the breed and discipline
expectations, age, and response to conservative therapies. This article addresses
the importance of the foal conformation examination to determine which foals need
surgical intervention to correct an angular deformity and when. Techniques for
surgical growth retardation include the transphyseal staple, screw and wire
transphyseal bridge, and transphyseal screw. Appropriate timing for intervention
for each location and complications associated with each procedure are discussed.
PMID- 28687096
TI - Surgical Management of Osteochondrosis in Foals.
AB - Osteochondrosis is common in young, athletic horses. Some lesions respond to
conservative therapy. Surgical management is the mainstay of treatment.
Arthroscopic debridement is useful in the femoropatellar joint, tarsocrural
joint, fetlock joint, and shoulder joint. Debridement is associated with good
outcomes, except in the shoulder joint. Osteochondrosis lesions in the elbow may
be difficult to access arthroscopically, thereby transosseous debridement.
Surgical management of subchondral cystic lesions of the medial femoral condyle
consists of debridement, debridement with grafting, transcondylar screws, and
intralesional corticosteroid injection. Surgical management is indicated with
lameness and persistent effusion, and in many horses intended for athletic use.
PMID- 28687097
TI - Foal Fractures: Osteochondral Fragmentation, Proximal Sesamoid Bone
Fractures/Sesamoiditis, and Distal Phalanx Fractures.
AB - Foals are susceptible to many of the same types of fractures as adult horses,
often secondary to external sources of trauma. In addition, some types of
fractures are specific to foals and occur routinely in horses under 1 year of
age. These foal-specific fractures may be due to the unique musculoskeletal
properties of the developing animal and may present with distinct clinical signs.
Treatment plans and prognoses are tailored specifically to young animals. Common
fractures not affecting the long bones in foals are discussed in this article,
including osteochondral fragmentation, proximal sesamoid bone
fractures/sesamoiditis, and distal phalanx fractures.
PMID- 28687098
TI - Physeal Fractures in Foals.
AB - Physeal fractures are common musculoskeletal injuries in foals and should be
included as a differential diagnosis for the lame or nonweightbearing foal.
Careful evaluation of the patient, including precise radiographic assessment, is
paramount in determining the options for treatment. Prognosis mostly depends on
the patient's age, weight, and fracture location and configuration.
PMID- 28687099
TI - Diagnosis and Treatment Considerations for Nonphyseal Long Bone Fractures in the
Foal.
AB - Many long bone fractures that are not considered repairable in the adult horse
are repairable in the foal. This is largely because of reduced patient size and
more rapid healing in the foal. When there is no articular communication, the
long-term prognosis for athletic function can be very good. Emergency care and
transport of the foal with a long bone fracture is different than the adult.
PMID- 28687100
TI - Prelude to an Equine Athlete: Foal Orthopedics.
PMID- 28687101
TI - Increased pancreatic cancer survival with greater lymph node retrieval in the
National Cancer Data Base.
AB - BACKGROUND: We evaluated the role of lymph node (LN) retrieval in pancreatic
adenocarcinoma (PA) patients undergoing pancreaticoduodenectomy (PD). METHODS: We
utilized the National Cancer Data Base; Cox regression models and logistic
regression models were used for statistical evaluation. RESULTS: We evaluated
26,792 patients with PA who underwent PD. The mean LN retrieved in LN(-) patients
was 10.8 vs 14.4 for LN(+) patients (P < 0.0001). Greater LN retrieval is an
independent predictor of a negative microscopic margin and decreased length of
stay. The median survival of LN(-) patients exceeded that of LN(+) patients (24.5
vs 15.1 months, P < 0.0001). Increasing LN retrieval is a significant predictor
of survival in all patients, and in LN(-) patients. The relationship of increased
LN retrieval and enhanced survival is a nearly linear trend. CONCLUSIONS: Rather
than demonstrating an inflection point that defines the extent of adequate
lymphadenectomy, this dataset demonstrates an incremental relationship between LN
retrieval and survival.
PMID- 28687102
TI - The Clinical Evaluation of Angioedema.
AB - The clinical evaluation of angioedema is reliant on obtaining a thorough patient
and family history with an assessment of risk factors and presenting symptoms
unique to each subtype. It is important to distinguish between angioedema with
and without urticaria as a primary step in the evaluation; thereafter, laboratory
parameters and investigations allow for subsequent stratification. There is a
significant disease burden associated with angioedema and thus it is essential
for health care practitioners to establish a prompt and accurate diagnosis, and a
comprehensive care plan that addresses the patient's physical and mental well
being alike.
PMID- 28687103
TI - Histaminergic Angioedema.
AB - Angioedema is frequently categorized into histamine- or bradykinin-mediated
disease. It is critical to determine the underlying mediator of symptoms as it
directs treatment. Histaminergic angioedema is the most frequent cause of
angioedema. It is classified as either acute (lasting <6 weeks) or chronic
(symptoms >6 weeks). It is further classified into angioedema presenting with or
without urticaria. Some patients with acute angioedema may have disease that
becomes chronic. Mast cells and basophils are central to the underlying
pathophysiology of histamine-mediated angioedema. The underlying treatments of
histamine-mediated angioedema are antihistamines, corticosteroids, and
epinephrine.
PMID- 28687104
TI - Angiotensin-converting Enzyme Inhibitor and Other Drug-associated Angioedema.
AB - Nonsteroidal antiinflammatory agents, beta-lactam antibiotics, non-beta lactam
antibiotics, and angiotensin-converting enzyme inhibitors are the most common
classes of drugs that cause angioedema. Drug-induced angioedema is known to occur
via mechanisms mediated by histamine, bradykinin, or leukotriene, and an
understanding of these mechanisms is crucial in guiding therapeutic decisions.
Nonallergic angioedema occurs in patients with genetic variants that affect
metabolism or synthesis of bradykinin, substance P, prostaglandins, or
leukotrienes, or when patients are taking drugs that have synergistic mechanisms.
The mainstay in treatment of nonallergic drug-induced angioedema is cessation of
the offending agents.
PMID- 28687105
TI - Acquired C1 Inhibitor Deficiency.
AB - Acquired angioedema due to C1-INH deficiency (C1-INH-AAE) can occur when there
are acquired (not inherited) deficiencies of C1-INH. A quantitative or functional
C1-INH deficiency with negative family history and low C1q is diagnostic of C1
INH-AAE. The most common conditions associated with C1-INH-AAE are autoimmunity
and B-cell lymphoproliferative disorders. A diagnosis of C1-INH-AAE can precede a
diagnosis of lymphoproliferative disease and confers an increased risk for
developing non-Hodgkin lymphoma. Treatment focuses on symptom control with
therapies that regulate bradykinin activity (C1-INH concentrate, icatibant,
ecallantide, tranexamic acid, androgens) and treatment of any underlying
conditions.
PMID- 28687106
TI - Pathogenesis of Hereditary Angioedema: The Role of the Bradykinin-Forming
Cascade.
AB - Hereditary angioedema (HAE) is an autosomal-dominant disorder owing to mutations
in the C1 inhibitor gene. Type I is characterized by a low C1 inhibitor protein
level and diminished functional activity, whereas type II has a normal (or
elevated) protein level but diminished function. When functional levels drop
beyond 40% of normal, attacks of swelling are likely to occur due to
overproduction of bradykinin. Angioedema can be peripheral, abdominal, or
laryngeal. The typical duration of episodes is 3 days. Therapies include C1
inhibitor replacement for prophylaxis or acute therapy, whereas inhibition of
kallikrein or blockade at the bradykinin receptor level can interrupt acute
episodes of swelling.
PMID- 28687107
TI - Laboratory Approaches for Assessing Contact System Activation.
AB - Hereditary angioedema (HAE) is a rare autosomal dominant disease clinically
characterized by recurrent, often unpredictable attacks of subcutaneous and
mucosal swelling. Acute episodes are debilitating, painful, disfiguring, and
potentially fatal. HAE type I and type II result from a deficiency in the plasma
level of functional C1 inhibitor. HAE with normal levels of C1 inhibitor has been
recognized. There is evidence that contact activation underlies the recurrent
attacks of swelling. This article reviews laboratory parameters to detect contact
system activation and implications for diagnosis of HAE and other forms of
bradykinin-mediated angioedema.
PMID- 28687108
TI - Acute Management of Hereditary Angioedema Attacks.
AB - Several treatment modalities have become available for management of acute
hereditary angioedema (HAE) attacks in the last 15 years. Most are now available
to patients in North America, Europe, United Kingdom, and Australia, but few
options exist in developing countries. Preferred contemporary use of the
treatments to be discussed is "on demand," because control remains with the
patient and delays in treatment access avoided. Four treatments-plasma-derived C1
inhibitor concentrate, recombinant C1 inhibitor concentrate, ecallantide, and
icatibant-are reviewed in this article. All have been shown to be superior to
placebo and effective in the management of all HAE attacks.
PMID- 28687109
TI - Prophylactic Therapy for Hereditary Angioedema.
AB - Long-term prophylaxis is needed in many patients with hereditary angioedema and
poses many challenges. Attenuated androgens are effective in many but are limited
by side effect profiles. There is less evidence for efficacy of tranexamic acid
and progestagens; however, the small side effect profile makes tranexamic acid an
option for prophylaxis in children and progestagens an option for women. C1
inhibitor is beneficial, but at present requires intravenous delivery and may
need dose titration for maximum efficacy. Short-term prophylaxis should be
considered for all procedures. New therapies are promising in overcoming many
problems encountered with current options for long-term prophylaxis.
PMID- 28687110
TI - Hereditary Angioedema with Normal C1 Inhibitor: Update on Evaluation and
Treatment.
AB - A new form of hereditary angioedema (HAE) was identified in the year 2000. Its
clinical appearance resembles HAE types I and II, which are caused by mutations
that result in a deficiency of C1 inhibitor (C1-INH). In patients with the new
form of HAE, C1-INH plasma levels and function values are normal, so it's termed
HAE with normal C1-INH (HAE-nC1). HAE-nC1, in a subgroup of patients, is thought
to be caused by mutations that affect the F12 gene. The diagnosis of HAE-nC1 is
based on history and clinical criteria. There are no licensed drugs with proven
treatment effects for HAE-nC1.
PMID- 28687112
TI - Burden of Illness and Quality-of-Life Measures in Angioedema Conditions.
AB - Burden of illness studies and evaluation of health-related quality of life using
validated questionnaires have become an important task in the comprehensive
management of angioedema conditions, mainly angioedema associated with chronic
spontaneous urticaria and hereditary angioedema caused by C1-inhibitor
deficiency. A review of the principal tools and studies is presented. Both
diseases present a higher proportion of psychiatric disorders, impair work and
studies productivity, and produce high direct and indirect costs. These
assessments also have been useful to evaluate the positive impact of new drugs
and interventions. More studies are desirable, especially in other types of
angioedema disorders, such as hereditary angioedema with normal C1 inhibitor.
PMID- 28687111
TI - Emerging Therapies in Hereditary Angioedema.
AB - Remarkable progress has been made in the treatment of bradykinin-mediated
angioedema with the advent of multiple new therapies. Patients now have effective
medications available for prophylaxis and treatment of acute attacks. However,
hereditary angioedema is a burdensome disease that can lead to debilitating and
dangerous angioedema episodes associated with significant costs for individuals
and society. The burden of treatment must be addressed regarding medication
administration difficulties, treatment complications, and adverse side effects.
New therapies are being investigated and may offer solutions to these challenges.
This article reviews the emerging therapeutic options for the treatment of HAE.
PMID- 28687113
TI - Pharmacoeconomics of Orphan Disease Treatment with a Focus on Hereditary
Angioedema.
AB - This article discusses orphan diseases, their prevalence, legislative incentives
to encourage development of therapies, and the impact of treatment on health care
payment systems. Specifically, the cost burden of hereditary angioedema on
patients, health care systems, and society is reviewed. The impact of
availability of and access to novel and specific therapies on morbidity,
mortality, and overall burden of disease is explored. Changes in treatment
paradigms to improve effect and reduce cost of treatment are presented.
PMID- 28687114
TI - Angioedema: An Orphan Symptom with Its Own Orphan Disease.
PMID- 28687115
TI - Angioedema: Challenges and Insights.
PMID- 28687116
TI - Is it Useful to Calculate Minimal Erythema Dose Before Narrowband UV-B
Phototherapy?
AB - INTRODUCTION AND OBJECTIVES: The starting dose for narrowband UV-B phototherapy
is determined by a patient's skin phototype or minimal erythema dose (MED).
Calculation of MED identifies patients with unsuspected photosensitivity. The aim
of this study was to investigate the influence of factors such as concomitant use
of photosensitizing agents, diagnosis, and combination with acitretin in patients
with psoriasis on the frequency and severity of adverse effects in patients with
a low MED to narrowband UV-B phototherapy. MATERIAL AND METHODS: We undertook a
retrospective observational cohort study between February 1, 2009 and March 31,
2015. MED values were classified as normal or low. RESULTS: In total, 302
patients with different skin conditions started narrowband UV-B phototherapy at a
dose determined by their MED. No differences were found between patients with a
low MED and those with a normal MED for number of drugs taken (P=.071) or use of
photosensitizing agents (P=0.806). Following adjustment for age, sex, and
phototype, the multivariate analysis showed that psoriasis exerted a protective
effect against a low MED (OR=0.31 [95% CI, 0.16-0.58]). No significant risk of
erythema or pruritus was detected in patients with a low MED (OR=1.68; 95% CI,
0.91-3.29 and OR=2.04; 95% CI, 0.99-4.22, respectively). CONCLUSIONS: Psoriasis
protects against a low MED. Although erythema and pruritus were more common in
patients with a low MED, the differences were not significant.
PMID- 28687117
TI - [Relapse after rhabdomyosarcoma in childhood and adolescence: Impact of an early
detection on survival].
AB - SUBJECT: Prognostic values of an early detection of a relapse after treatment of
a localized rhabdomyosarcoma and the interest of performing systematic radiologic
assessment after treatment have not yet been evaluated in Europe. MATERIAL AND
METHODS: Modalities of relapse of 99 patients under 20 years of age, after an
initially localized rhabdomyosarcoma, treated in 9 French centers ("Societe
francaise des cancers de l'enfant" consortium) have been analyzed. Prognostic
value of the protocol compliance during the observation period after therapy has
been evaluated. RESULTS: Relapses have been diagnosed in 59 cases by a "symptom"
the child was complaining of, in 12 cases because of "physical signs" detected
during the clinical examination of a systematic consultation and in 27 cases
thanks to "systematic follow-up imaging" (missing data: 1 case). Survival after
relapse at 3 years was 47.5 % (IC95 %: 37.1 %-57.1 %). Diagnosis of the relapse
is established earlier in the group "systematic imaging" rather than with other
methods of detection ("symptom", "physical signs"), (P= 0.025), with detection of
smaller tumors (<= 5 cm ; 100.0 % vs. 60.9 % vs. 77.8 %, P= 0.007) but without
possibility of reaching a second remission (70.4 % vs. 50.8 % vs. 50.0 % P=
0.37), nor significant impact on 5-year overall survival (47.1 % vs. 47.1 % vs.
48.6 % P= 0.94). CONCLUSION: Current methods of systematic surveillance after a
first-line treatment of an initially localized rhabdomyosarcoma seem to improve
the earliness of the diagnosis, but not the prognosis of the relapse.
PMID- 28687118
TI - Macroinvertebrate community responses to hydrological controls and groundwater
abstraction effects across intermittent and perennial headwater streams.
AB - Intermittent rivers comprise a significant proportion of river networks globally
and their spatial extent is predicted to increase with rising water abstraction
pressures. Despite this, the ecological implications of hydrological
modifications within intermittent rivers have received limited research
attention. This paper examines macroinvertebrate assemblages across intermittent
and perennial sections of headwater streams within the Hampshire Avon catchment
(United Kingdom) over a five-year period. The composition of faunal assemblages
was quantified in relation to four hydrological metrics: the duration of flowing
conditions, the geographical proximity to the nearest perennial source along each
watercourse (two observed flow parameters) and two modelled groundwater
abstraction influences. The results highlight that macroinvertebrate communities
inhabiting sites which dry periodically and are positioned at greater distances
(>c. 2.5km) above the perennial source (the most upstream point of permanent flow
within a given year) possessed the highest conservation values. These sites
supported species that are rare in many areas of Europe (e.g. Ephemeroptera:
Paraletophlebia werneri) or with limited geographical distribution across the
United Kingdom (e.g. Trichoptera: Limnephilus bipunctatus). A range of faunal
community diversity indices were found to be more sensitive to the antecedent
flow duration and distance from the perennial source, rather than any effects of
groundwater abstraction. Taxonomic richness responded most strongly to these
observed flow parameters and varied more markedly with the distance from the
perennial source compared to the antecedent flow duration. Several taxa were
significantly associated with the observed flow parameters, particularly those
predominantly inhabiting perennially flowing systems. However, the distance that
such fauna could migrate into intermittent reaches varied between taxa. This
research demonstrates the overriding importance of antecedent flow durations and
the geographical proximity to perennial sources on macroinvertebrate communities
within intermittent and perennial headwater streams.
PMID- 28687119
TI - Statistical learning of speech sounds is most robust during the period of
perceptual attunement.
AB - Although statistical learning has been shown to be a domain-general mechanism,
its constraints, such as its interactions with perceptual development, are less
well understood and discussed. This study is among the first to investigate the
distributional learning of lexical pitch in non-tone-language-learning infants,
exploring its interaction with language-specific perceptual attunement during the
first 2years after birth. A total of 88 normally developing Dutch infants of 5,
11, and 14months were tested via a distributional learning paradigm and were
familiarized on a unimodal or bimodal distribution of high-level versus high
falling tones in Mandarin Chinese. After familiarization, they were tested on a
tonal contrast that shared equal distributional information in either modality.
At 5months, infants in both conditions discriminated the contrast, whereas 11
month-olds showed discrimination only in the bimodal condition. By 14months,
infants failed to discriminate the contrast in either condition. Results indicate
interplay between infants' long-term linguistic experience throughout development
and short-term distributional learning during the experiment, and they suggest
that the influence of tonal distributional learning varies along the perceptual
attunement trajectory, such that opportunities for distributional learning
effects appear to be constrained in the beginning and at the end of perceptual
attunement. The current study contributes to previous research by demonstrating
an effect of age on learning from distributional cues.
PMID- 28687120
TI - Safety effects of dynamic speed limits on motorways.
AB - Dynamic speed limits (DSL) are limits that change according to real-time traffic,
road or weather conditions. In DSL-schemes road users are typically informed of
speed limit changes by electronic signs that are housed within gantries situated
above lanes. Dynamic speed limit systems are increasingly applied worldwide,
usually on motorways. One of the objectives of dynamic speed limits is to improve
traffic safety through reductions in speed variations within and across lanes and
between upstream and downstream flows. This paper shows the results of an
empirical evaluation of the effects on traffic safety of a dynamic speed limit
system on motorways in Flanders, Belgium. The evaluation was done by means of a
before-after analysis of crashes, completed with a cost-benefit analysis. The
results show that the number of injury crashes decreased significantly (-18%)
after the introduction of the system. A separate analysis for serious and fatal
injury crashes revealed a non-significant decrease of 6%. A distinction according
to crash type showed an almost significant decrease of 20% in the number of rear
end crashes whereas the number of single-vehicle crashes decreased by 15% (ns).
However, no effect was found for side crashes. In addition to the analysis of the
effects, a cost-benefit analysis was applied. The costs of the implementation of
these systems were compared with the benefits of crash prevention. The cost
benefit analyses of the crash effects showed a benefits-to-costs ratio of
approximately 0.7, which means that the costs tend to exceed the benefits. Taking
into account the important margins of uncertainty with respect to both costs and
benefits, we have also explored how the net benefits are affected by some key
assumptions. The general conclusion is that there is no convincing evidence that
the costs of the system currently outweigh the expected benefits in terms of
crash prevention.
PMID- 28687121
TI - New imaging techniques in retinal vasculitis.
AB - The term retinal vasculitis (RV) encompasses a heterogeneous group of sight
threatening conditions that are included in the intraocular inflammatory diseases
that affect the posterior segment of the eye. Based on the nature of the
inflammatory process, RV are classified into predominantly inflammatory or
ischaemic (occlusive RV). The diagnosis is clinical and the aetiology can be
infectious or non-infectious (immune-mediated). RV can be an isolated ocular
syndrome or be associated with a systemic disease, of which they can represent
the first manifestation. New retinal imaging techniques such as ultra-wide field
fluorescein angiography and optical coherence tomography angiography will help us
classify the RV and aid the diagnostic process, which can be challenging and
require a multidisciplinary approach. Therefore, clinical knowledge of RV is
essential for prompt diagnosis and to establish the appropriate treatment.
PMID- 28687122
TI - Evaluation of ex-vivo 9.4T MRI in post-surgical specimens from temporal lobe
epilepsy patients.
AB - PURPOSE: This study evaluates hippocampal pathology through usage of ultra-high
field 9.4T ex-vivo imaging of resected surgical specimens in patients who have
undergone temporal lobe epilepsy surgery. METHOD AND MATERIALS: This is a
retrospective interpretation of prospectively acquired data. MRI scanning of
resected surgical specimens from patients who have undergone temporal lobe
epilepsy surgery was performed on a 9.4T small bore Varian MR magnet. Structural
images employed a balanced steady-state free precession sequence (TrueFISP). Six
patients (3 females; 3 males) were included in this study with an average age at
surgery of 40.7 years (range 20Y_"60) (one was used as a control reference). Two
neuroradiologists qualitatively reviewed the ex-vivo MRIs of resected specimens
while blinded to the histopathology reports for the ability to identify abnormal
features in hippocampal subfield structures. RESULTS: The hippocampal subfields
were reliably identified on the 9.4T ex-vivo scans in the hippocampal head region
and hippocampal body region by both neuroradiologists in all 6 patients. There
was high concordance to pathology for abnormalities detected in the CA1, CA2, CA3
and CA4 subfields. Detection of abnormalities in the dentate gyrus was also high
with detection in 4 of 5 cases. The Cohen's kappa between the two
neuroradiologists was calculated at 0.734 SE=0.102. CONCLUSIONS: Ex-vivo 9.4T
specimen imaging can detect abnormalities in CA1, CA2, CA3, CA4 and DG in both
the hippocampal head and body. There was good concordance between qualitative
findings and histopathological abnormalities for CA1, CA2, CA3, CA4 and DG.
PMID- 28687123
TI - Dynamics of cerebral perfusion deficits after aneurysmal SAH - predictive value
of early MTT for subsequent MTT deterioration.
AB - BACKGROUND AND PURPOSE: The pathogenesis of poor functional outcome after
aneurysmal subarachnoid hemorrhage (aSAH) is not fully understood.
Microcirculatory dysfunction, which can be indirectly measured by CT perfusion
(CTP), is assumed to play a central role. We evaluated the predictive value of
early changes in microcirculation for secondary critical perfusion changes.
MATERIALS AND METHODS: Out of 351 consecutive aSAH patients, 166 patients with
>=1 CTP within 72h of ictus (early CTP) and >=3 CTPs in total were included in
the retrospective analysis (53.2+/-12.4years of age). Receiver-operating
characteristic (ROC) analysis was performed to identify the mean transit time
(MTT) threshold in early CTP with the highest sensitivity and specificity for
predicting secondary critical perfusion changes >72h after ictus. The odds ratio
was calculated and the threshold for the highest odds ratio was determined.
RESULTS: Secondary critical perfusion changes were observed in 67/166 patients
(40.4%). An early MTT 1.3 times the mean normal MTT could predict those changes
with an odds ratio of 2.67 (sensitivity 67.2%, specificity 56.6%). Shifting the
threshold to 1.26 times the mean normal MTT resulted in an odds ratio of 3.56
(sensitivity 79.1%, specificity 48.5%). CONCLUSIONS: Early MTT is predictive of
secondary critical perfusion changes, which could have applications for
neuromonitoring and treatment.
PMID- 28687125
TI - ?
PMID- 28687124
TI - Role of Global Longitudinal Strain in Predicting Outcomes in Hypertrophic
Cardiomyopathy.
AB - Global longitudinal strain (GLS) is a sensitive indicator of global left
ventricular function particularly in those with normal ejection fraction. We
examined the potential value of GLS in predicting outcomes in hypertrophic
cardiomyopathy (HC). Conventional and strain echocardiography was performed in
400 patients with HC followed for a median 3.1 years (interquartile range 1.2 to
5.6). Peak systolic strain from 3 apical views was averaged to calculate GLS.
Patients were divided based on a previously published cutoff value of -16%.
Additionally, we identified 4 HC subgroups based on GLS: GLS <= -20%, -20% < GLS
<= -16%, -16% < GLS <= -10%, and GLS > -10%. The primary end point was a
composite of new-onset sustained ventricular tachycardia/fibrillation, heart
failure, cardiac transplantation, and all-cause death. Patients with GLS > -16%
had significantly more events (17% vs 7%, p = 0.002). In the 4-group analysis,
event rates increased with worsening GLS (5%, 7%, 14%, and 33%, respectively, p =
0.001). Event-free survival was significantly superior in those with GLS <= -16%
versus GLS > -16% (p = 0.004); similarly, GLS > -10% portended a significantly
worse event-free survival compared with each of the other 3 groups (p <0.01 for
all pairwise comparisons). By univariate and multivariate Cox regression
analysis, GLS remained significantly associated with the composite end point. GLS
> -10% had 4 times the risk of events compared with GLS <= -16% (p = 0.006). In
conclusion, echo-based GLS is independently associated with outcomes in HC.
Patients with GLS > -10% have significantly higher event rates.
PMID- 28687126
TI - ?
PMID- 28687127
TI - [Heart failure and nursing homes].
AB - Heart failure is a very common condition in elderly people, particularly those
living away from home, in institutional care. The main objective of a study was
to find out whether patients with heart failure admitted to a nursing home
benefit or not from the same ultrasound assessment as the general population. The
secondary objective was to analyse the management of residents with heart failure
living in institutional care.
PMID- 28687128
TI - [Assessment of the use of music therapy with nursing home residents].
AB - A study analysed, on the one hand, the efficacy of the use of music therapy with
residents and, on the other, the feasibility of the implementation of such a
technique in nursing homes and in follow-up and rehabilitation units. In this
context, music therapy seems to be an effective alternative to traditional
approaches.
PMID- 28687129
TI - [From dependency to autonomy, a geriatric pathway].
AB - Preventing dependency is essential in our ageing society. One of its components
is the avoidable dependency which develops during a period of hospitalisation.
Caregivers play an important role in helping the elderly person regain their
autonomy. Various actions have been undertaken on this theme within the
gerontology unit of Toulouse university hospital, including the creation of a
multi-disciplinary group of experts among the caregivers working in the unit.
PMID- 28687130
TI - [Training and action research in a short-stay geriatric oncology unit].
AB - A participative action research project was undertaken in a geriatric oncology
hospital unit. It resulted in the training of paramedical staff regarding the
specific care to be provided to elderly people with cancer.
PMID- 28687131
TI - [Study of patients benefiting from a geriatric oncology assessment].
AB - A retrospective study carried out in 2014 focused on the 124 geriatric oncology
consultations carried out at Saint-Etienne university hospital. The opinion of
the geriatric oncologist was evidently incorporated into the treatment plan, with
requests for early assessments. The geriatric oncologist often recommended a
specific curative treatment and the majority of assessments were followed up by
the oncologist. The benefit of the liaison between the oncologist and
gerontologist with regard to the patient's care was clearly demonstrated.
PMID- 28687132
TI - [Sleep and nocturnal incontinence in hospital or institutional care].
AB - A survey carried out in 2004 studied the link between quality of sleep and the
nocturnal management of incontinence. This same survey was repeated 10 years
later. The results reveal the impact on quality of sleep, the deteriorating
management of incontinence with the lenghtening of waiting time and the causes of
waking. This discussion process on the quality of sleep must continue.
PMID- 28687134
TI - ?
PMID- 28687133
TI - ?
PMID- 28687136
TI - Erratum to "Changing prevalence and treatment outcomes of patients with p16 human
papillomavirus related oropharyngeal squamous cell carcinoma in New Zealand" [Br
J Oral Maxillofac Surg 54 (8) (2016) 898-903].
PMID- 28687135
TI - Advance care planning within survivorship care plans for older cancer survivors:
A systematic review.
AB - Advances in the medical treatment of cancer have increased the number of
survivors, particularly among older adults, who now represent the majority of
these. Survivorship care plans (SCPs) are documents that cancer patients receive
summarising their care, usually at the end of treatment but preferably from
initial diagnosis. These may increase patient satisfaction and represent an
opportunity to initiate preventative strategies and address future care needs.
Advance care planning (ACP), incorporating advance healthcare decision-making,
including formal written directives, increases satisfaction and end-of-life care.
This paper systematically reviews evaluations of ACP within SCPs among older
(>=65 years) cancer survivors. No studies meeting the inclusion criteria were
identified by search strategies conducted in PubMed/MEDLINE and the Cochrane
databases. One paper examined cancer survivors' mainly positive views of ACP.
Another discussed the use of a SCP supported by a 'distress inventory' that
included an advance care directive (living will) as an issue, though no formal
evaluation was reported. Although ACP is important for older adults, no study was
found that evaluated its role within survivorship care planning. Despite the risk
of recurrence and the potential for morbidity and mortality, especially among
older cancer survivors, ACP is not yet a feature of SCPs.
PMID- 28687138
TI - Retraction notice to Aerobic degradation of 4-nitroaniline (4-NA) via novel
degradation intermediates by Rhodococcus sp. strain FK48 [HAZMAT 254-255 (2013)
72-78].
PMID- 28687137
TI - [Diagnosis and management of acquired immune haemolytic anaemia excluding
neoplasia. Adequacy with the current guidelines published in 2009].
AB - OBJECTIVES: Describe the management of Acquired Immune Haemolytic Anaemia (AIHA)
and correlate with the current guidelines published in 2009. The secondary
objective was to calculate the positive predictive value of the Direct
Antiglobulin Test (DAT) for the diagnosis of AIHA. METHODS: A retrospective and
monocentric study was performed from 2010 to 2015 based on positive DATs,
identified in the French Blood Agency database or in medical files. All patients
managed for initial diagnosis or relapse of AIHA were included, excluding
neoplasia. RESULTS: Six hundred and twenty-three patients had a positive DAT, 42
had non-neoplastic AIHA. Thirty-nine patients were included, 32 had warm
antibodies, 5 had a negative DAT and 2 had cold antibodies. No cause was found
for 46% (17/37) of the warm antibody and negative DATs AIHAs. Autoimmune disease
was found in 11 cases (30%), infection in 4 cases (11%). The etiologic
investigations were consistent with the guidelines in 49% of cases.
Corticosteroids were first prescribed, as recommended. Second-line treatments
were rituximab in 9 cases, splenectomy in 4 cases and azathioprine in 3 cases.
The management of cold antibody AIHA complied with the guidelines. The positive
predictive value of DATs in hospitalized population was of 14% (85/610).
CONCLUSION: AIHA guidelines seem insufficiently applied in our center.
PMID- 28687139
TI - Reply to "Deprescribing and shared decision making in Internal Medicine".
PMID- 28687140
TI - Stroke is now a brain disease: Revising ICD-11.
PMID- 28687141
TI - Educational interventions and promotion of changes in the practices of prevention
and monitoring of delirium in critical patient.
PMID- 28687142
TI - Common and diagnosis-specific fractional anisotropy of white matter in
schizophrenia, bipolar disorder, and major depressive disorder: Evidence from
comparative voxel-based meta-analysis.
PMID- 28687143
TI - Contemporary Treatment Patterns and Outcomes for Clinical Stage IS Testicular
Cancer.
AB - BACKGROUND: Controversy exists regarding the optimal management strategy for
clinical stage IS seminomatous (SGCT) and nonseminomatous germ cell tumors
(NSGCT) of the testis. OBJECTIVE: To assess contemporary treatment patterns and
outcomes for clinical stage IS testicular cancer. DESIGN, SETTING, AND
PARTICIPANTS: Using the National Cancer Data Base (2004-2012), we identified 1362
patients with clinical stage IS SGCT and NSGCT of the testis, treated with either
adjuvant treatment (AT) or observation. OUTCOME MEASURES AND STATISTICAL
ANALYSIS: We calculated the annual percent change (APC) to assess treatment
trends. Inverse probability of treatment weighting (IPTW)-adjusted Kaplan-Meier
curves and Cox regression analyses were used to compare overall survival (OS)
between AT and observation groups. Analyses were stratified by histologic type.
RESULTS AND LIMITATIONS: Overall, there were 581 (43%) and 781 (57%) men with
SGCT and NSGCT, respectively. Among men with SGCT, the use of AT decreased over
the study period (APC=-2.7, 95% confidence interval [CI]: -4.4, -1.1, p=0.001).
The 5-yr IPTW-adjusted rates of OS were 99% and 97% in the AT and observation
groups, respectively (hazard ratio = 0.36, 95% CI: 0.12, 1.14, p=0.08). Among men
with NSGCT, the use of AT remained stable over the study period (APC = +0.8, 95%
CI: -0.7, +2.2, p=0.29). The 5-yr IPTW-adjusted rates of OS were 97% and 95% in
the AT and observation groups, respectively (HR=0.66, 95% CI: 0.27, 1.61,
p=0.36). Limitations include the lack of full treatment details and cancer
specific survival information. CONCLUSIONS: Trends in the use of AT significantly
decreased over time for SGCT, while it remained stable for NSGCT. Nonetheless, we
report 5-yr OS rates of >=95% for both histologies without any significant
benefit with the use of AT. Further studies are warranted to confirm these
findings. PATIENT SUMMARY: We evaluated treatment trends and outcomes for stage
IS testicular cancer. We found that treatment changed over time for seminoma and
remained stable for nonseminoma; there was no significant survival benefit in the
use of adjuvant treatment versus observation for both seminomatous and
nonseminomatous germ cell tumors.
PMID- 28687144
TI - Re: The Prostate Health Index Adds Predictive Value to Multi-parametric MRI in
Detecting Significant Prostate Cancers in a Repeat Biopsy Population.
PMID- 28687145
TI - Re: Eric A. Klein, Arnon Chait, Jason M. Hafron, et al. The Single-parameter,
Structure-based IsoPSA Assay Demonstrates Improved Diagnostic Accuracy for
Detection of Any Prostate Cancer and High-grade Prostate Cancer Compared to a
Concentration-based Assay of Total Prostate-specific Antigen: A Preliminary
Report. Eur Urol 2017;72:942-9: The Most Appropriate IsoPSA Cutoff for Diagnosis
of Prostate Cancer.
PMID- 28687146
TI - Intravenous dexmedetomidine for cesarean delivery and its concentration in
colostrum.
AB - BACKGROUND: Dexmedetomidine is a sedative agent with high alpha2-adrenoreceptor
selectivity. We investigated intravenous dexmedetomidine administration during
scheduled cesarean delivery under neuraxial anesthesia; and its concentration in
the colostrum. METHODS: Twenty-seven participants having elective cesarean
delivery under combined spinal-epidural anesthesia were enrolled. After delivery
and cord clamping, 6MUg/kg/h of intravenous dexmedetomidine was administered for
10minutes, followed by a dose of 0.7MUg/kg/h until peritoneal closure. Sedation,
vital signs and side effects were recorded. Blood and colostrum samples were
collected from each participant at 6, 12, and 24h after dexmedetomidine
administration. Samples were analysed using liquid chromatography tandem-mass
spectroscopy. RESULTS: Colostrum samples were collected from 10 patients. The
median [95% CI] plasma dexmedetomidine concentration was 333 [303-534] pg/ml at
0h and 19.7 [13.5-25.8] pg/ml at 6h. The colostrum concentration was 12.3 [8.1
20.1] pg/ml at 6h. The dexmedetomidine completely disappeared from both within
24h. The calculated milk-to-plasma ratio at 6h was 0.76 [0.57-0.86]. The relative
infant dose was 0.034% [0.020-0.062%]. At dexmedetomidine discontinuation, the
Richmond Agitation-Sedation Scale score was -2 (range,-4 to -1). During surgery,
no patients complained of nausea, peritoneal irritation or afterbirth pain.
CONCLUSIONS: The dexmedetomidine milk-to-plasma ratio did not exceed 1 in any
participant, and the relative infant dose was very low. Maternal sedation using
dexmedetomidine is unlikely to be harmful for the infant.
PMID- 28687147
TI - Radiofrequency ablation compared to surgical resection for curative treatment of
patients with colorectal liver metastases - a meta-analysis.
AB - BACKGROUND: Hepatic resection and ablative treatments, such as RFA are available
treatment options for liver tumors. Advantages and disadvantages of these
treatment options in patients with colorectal liver metastases need further
evaluation. The purpose of this study was to systematically evaluate the role of
radiofrequency ablation (RFA) compared to surgery in the curative treatment of
patients with colorectal liver metastases (CRLM). METHODS: A systematic search
was performed from MEDLINE, EMBASE and the Cochrane Library for studies directly
comparing RFA with resection for CRLM, after which variables were evaluated.
RESULTS: RFA had significantly lower complication rates (OR = 0.44, 95% CI = 0.26
0.75, P = 0.002) compared to resection. However, RFA showed a higher rate of any
recurrence (OR = 1.66, 95% CI = 1.15-2.40, P = 0.007), local recurrence (OR =
9.56, 95% CI = 6.85-13.35, P = 0.001), intrahepatic recurrence (OR = 1.96, 95% CI
= 1.34-2.87, P = 0.001) and extrahepatic recurrence (OR = 1.21, 95% CI = 0.90
1.63, P = 0.22). Also, 5-year disease-free survival (OR = 2.20, 95% CI = 1.28
3.79, P = 0.005) and overall survival (OR = 2.35, 95% CI = 1.49-3.69, P = 0.001)
were significantly lower in patients treated with RFA. CONCLUSIONS: RFA showed a
significantly lower rate of complications, but also a lower survival and a higher
rate of recurrence as compared to surgical resection. All the included studies
were subject to possible patient selection bias and therefore randomized clinical
trials are needed to accurately evaluate these treatment modalities.
PMID- 28687148
TI - 99mTc-mebrofenin hepatobiliary scintigraphy predicts liver failure following
major liver resection for perihilar cholangiocarcinoma.
AB - BACKGROUND: Posthepatectomy liver failure (PHLF) is a threatening complication
after liver surgery, especially in perihilar cholangiocarcinoma (PHC). This study
aimed to assess the value of preoperative assessment of liver function using
99mTc-mebrofenin hepatobiliary scintigraphy (HBS) to predict PHLF in comparison
with liver volume in PHC patients. METHODS: All patients who underwent resection
of suspected PHC in a single center between 2000 and 2015 were included in the
analysis. PHLF was graded according to the ISGLS criteria with grade B/C
considered clinically relevant. A cut-off value for the prediction of PHLF was
calculated using the receiver operating characteristic curve (ROC) analysis.
RESULTS: A total of 116 patients were included of which 27 (23%) suffered of
PHLF. ROC values for the prediction of PHLF were 0.74 (0.63-0.86) for future
liver remnant function and 0.63 (0.47-0.80) for volume. A cut-off for liver
function was set at 8.5%/min, which resulted in a negative predictive value of
94% and positive predictive value of 41%. CONCLUSIONS: Assessment of liver
function with HBS had better predictive value for PHLF than liver volume in
patients undergoing major liver resection for suspected PHC. The cut-off of
8.5%/min can help to select patients for portal vein embolization and might help
to reduce postoperative liver failure.
PMID- 28687149
TI - Stiffness of a wobbling mass models analysed by a smooth orthogonal decomposition
of the skin movement relative to the underlying bone.
AB - The so-called soft tissue artefacts and wobbling masses have both been widely
studied in biomechanics, however most of the time separately, from either a
kinematics or a dynamics point of view. As such, the estimation of the stiffness
of the springs connecting the wobbling masses to the rigid-body model of the
lower limb, based on the in vivo displacements of the skin relative to the
underling bone, has not been performed yet. For this estimation, the
displacements of the skin markers in the bone-embedded coordinate systems are
viewed as a proxy for the wobbling mass movement. The present study applied a
structural vibration analysis method called smooth orthogonal decomposition to
estimate this stiffness from retrospective simultaneous measurements of skin and
intra-cortical pin markers during running, walking, cutting and hopping. For the
translations about the three axes of the bone-embedded coordinate systems, the
estimated stiffness coefficients (i.e. between 2.3kN/m and 55.5kN/m) as well as
the corresponding forces representing the connection between bone and skin (i.e.
up to 400N) and corresponding frequencies (i.e. in the band 10-30Hz) were in
agreement with the literature. Consistently with the STA descriptions, the
estimated stiffness coefficients were found subject- and task-specific.
PMID- 28687150
TI - Virtually optimized insoles for offloading the diabetic foot: A randomized
crossover study.
AB - : Integration of objective biomechanical measures of foot function into the
design process for insoles has been shown to provide enhanced plantar tissue
protection for individuals at-risk of plantar ulceration. The use of virtual
simulations utilizing numerical modeling techniques offers a potential approach
to further optimize these devices. In a patient population at-risk of foot
ulceration, we aimed to compare the pressure offloading performance of insoles
that were optimized via numerical simulation techniques against shape-based
devices. Twenty participants with diabetes and at-risk feet were enrolled in this
study. Three pairs of personalized insoles: one based on shape data and
subsequently manufactured via direct milling; and two were based on a design
derived from shape, pressure, and ultrasound data which underwent a finite
element analysis-based virtual optimization procedure. For the latter set of
insole designs, one pair was manufactured via direct milling, and a second pair
was manufactured through 3D printing. The offloading performance of the insoles
was analyzed for forefoot regions identified as having elevated plantar
pressures. In 88% of the regions of interest, the use of virtually optimized
insoles resulted in lower peak plantar pressures compared to the shape-based
devices. Overall, the virtually optimized insoles significantly reduced peak
pressures by a mean of 41.3kPa (p<0.001, 95% CI [31.1, 51.5]) for milled and
40.5kPa (p<0.001, 95% CI [26.4, 54.5]) for printed devices compared to shape
based insoles. The integration of virtual optimization into the insole design
process resulted in improved offloading performance compared to standard, shape
based devices. CLINICAL TRIAL REGISTRATION: ISRCTN19805071, www.ISRCTN.org.
PMID- 28687151
TI - Control of lateral weight transfer is associated with walking speed in
individuals post-stroke.
AB - Restoring functional gait speed is an important goal for rehabilitation post
stroke. During walking, transferring of one's body weight between the limbs and
maintaining balance stability are necessary for independent functional gait.
Although it is documented that individuals post-stroke commonly have difficulties
with performing weight transfer onto their paretic limbs, it remains to be
determined if these deficits contributed to slower walking speeds. The primary
purpose of this study was to compare the weight transfer characteristics between
slow and fast post-stroke ambulators. Participants (N=36) with chronic post
stroke hemiparesis walked at their comfortable and maximal walking speeds on a
treadmill. Participants were stratified into 2 groups based on their comfortable
walking speeds (>=0.8m/s or <0.8m/s). Minimum body center of mass (COM) to center
of pressure (COP) distance, weight transfer timing, step width, lateral foot
placement relative to the COM, hip moment, peak vertical and anterior ground
reaction forces, and changes in walking speed were analyzed. Results showed that
slow walkers walked with a delayed and deficient weight transfer to the paretic
limb, lower hip abductor moment, and more lateral paretic limb foot placement
relative to the COM compared to fast walkers. In addition, propulsive force and
walking speed capacity was related to lateral weight transfer ability. These
findings demonstrated that deficits in lateral weight transfer and stability
could potentially be one of the limiting factors underlying comfortable walking
speeds and a determinant of chronic stroke survivors' ability to increase walking
speed.
PMID- 28687152
TI - Valorisation of chicken feathers: Characterisation of chemical properties.
AB - The characterisation of the chemical properties of the whole chicken feather and
its fractions (barb and rachis), was undertaken to identify opportunities for
valorizing this waste product. The authors have described the physical,
morphological, mechanical, electrical and thermal properties of the chicken
feathers and related them to potential valorisation routes of the waste. However,
identification of their chemical properties is necessary to complete a
comprehensive description of chicken feather fractions. Hence, the chicken
feathers were thoroughly characterised by proximate and ultimate analyses,
elemental composition, spectroscopic analyses, durability in different solvents,
burning test, and hydrophobicity. The proximate analysis of chicken feathers
revealed the following compositions: crude lipid (0.83%), crude fibre (2.15%),
crude protein (82.36%), ash (1.49%), NFE (1.02%) and moisture content (12.33%)
whereas the ultimate analyses showed: carbon (64.47%), nitrogen (10.41%), oxygen
(22.34%), and sulphur (2.64%). FTIR analysis revealed that the chicken feather
fractions contain amide and carboxylic groups indicative of proteinious
functional groups; XRD showed a crystallinity index of 22. Durability and burning
tests confirmed that feathers behaved similarly to animal fibre. This reveals
that chicken feather can be a valuable raw material in textile, plastic,
cosmetics, pharmaceuticals, biomedical and bioenergy industries.
PMID- 28687153
TI - Beyond the Buzz: The Maturing of Technology Use in Geriatric Psychiatry.
PMID- 28687154
TI - Safety and efficacy for laparoscopic versus open hepatectomy: A meta-analysis.
AB - BACKGROUND: Laparoscopic hepatectomy (LH) is growing in popularity, but its
efficacy and safety are still controversial. Few multicenter, large, population
based, prospective, randomized studies have compared LH with open hepatectomy
(OH). We performed a meta-analysis to compare the treatment outcome of patients
undergoing LH versus OH. METHODS: We searched PubMed, EMBASE, Cochrane Central
Register, CNKI, and WanFang Med Online databases to November 30th, 2016 for
randomized controlled trials (RCTs) that compared treatment outcome for LH and
OH. Eligibility criteria included evaluation of operation time, blood loss,
complications, and hospital stay after surgery for adult patients who underwent
LH or OH. Reviewers in pairs independently screened the studies, extracted data
and assessed the risk of bias of included studies. Agreement was achieved. RevMan
5.3 was used to conduct meta-analysis. Complete case analysis was used as primary
analysis. Predefined subgroup analysis includes benign and malignant disease.
RESULTS: Eight RCTs with a total of 554 patients were included in the meta
analysis, 275 types of LH and 279 types of OH. LH reduced the hospital stay after
surgery (8 trials, 554 patients, MD = -3.84 days, 95%CI: -5.05 to -2.63, P <
0.0001, I2 = 88%) and the complication rate (8 trials, 554 patients, RR = 0.29,
95%CI: 0.17-0.50, P < 0.0001, I2 = 0%, absolute 13 to 40 fewer), shortened the
time to first flatus (3 trials, 264 patients, MD = -1.41 days, 95%CI: -1.98 to
0.83, P < 0.0001, I2 = 92%), and had less blood loss (8 trials, 554 patients, MD
= -164.31 ml, 95%CI: -220.91 to -107.72, P < 0.0001, I2 = 98%) without increasing
the operation time (MD = -7.96 min, 95%CI: -24.99 to 9.07, P = 0.36, I2 = 91%)
compared with OH. CONCLUSIONS: Laparoscopy is more effective in terms of hospital
stay after surgery and time to first flatus with fewer blood loss and
complication rate for hepatic resection compared with open surgery.
PMID- 28687155
TI - Exophytic papillary penile cancer.
AB - Penile carcinoma is a rare disease that has a wide range of pathology and
morbidity. Occurs commonly in the 6th and 7th decades of life. Squamous cell
carcinoma (SCC) is the predominant histological type. We present a case of a
penile lesion of exophytic papillary morphology accompanied by multiple bilateral
mobile inguinal lymph nodes.
PMID- 28687156
TI - [Description of a clinical typology specific to men whose urinary symptoms
require anticholinergic treatment].
AB - OBJECTIVES: To describe, using cluster analysis methods, the existence of a
clinical typology specific to men, who are responding or not to anticholinergic
treatment, and identify predictive factors associated with treatment success.
METHODS: An observational study was conducted in consecutive male patients who
were prescribed anticholinergics for the first time. Sociodemographic data,
patient characteristics, urinary symptom profile (USP) questionnaire, Ditrovie
scale and symptom severity were assessed at inclusion and after 3 months of
treatment. A cluster analysis according the hierarchical classification of Ward
was used to discriminate two clusters (low and strong persistence of urinary
disorders, respectively). Logistic regression was used to identify factors
associated with evolution of treatment satisfaction and symptoms. RESULTS: Out of
1018 patients evaluated, 410 had available follow-up data. A treatment with
anticholinergic was prescribed to all of patient among which solifenacin
represented 92.4% and 27.6% of patients received also an alpha-blocker. Cluster
analysis identified two populations of responders. Recent symptoms, young age,
absence of obesity or associated treatment, and urgency without incontinence were
associated with a better clinical outcome under treatment. The USP questionnaire
showed voiding difficulties in 12.4% of patients, and the only associated factor
was symptom duration before consultation. CONCLUSIONS: Anticholinergics are
efficacious for management of storage lower urinary tract symptom management in
men. Clinical factors (age, obesity, treatments, urge urinary incontinence) could
influence treatment outcome and allow a better patient selection for clinical
decision-making. LEVEL OF EVIDENCE: 4.
PMID- 28687157
TI - The pattern of failure and predictors of locoregional control in lateralized
buccogingival cancer after postoperative radiation therapy.
AB - BACKGROUND: To evaluate the failure pattern and identify predictors of
locoregional control in lateralized buccogingival cancer after postoperative
radiotherapy (RT) at a single institution. METHODS: We retrospectively reviewed
the clinical data of 150 patients with lateralized oral squamous cell carcinoma,
including carcinoma of the buccal mucosa, gingiva and retromolar trigone. All
patients underwent radical surgery followed by postoperative RT with or without
concurrent chemotherapy. We registered planning computer tomography images with
images obtained at recurrence and categorized the failure pattern as in-field,
marginal, or out-field recurrence. RESULTS: The median follow-up duration was 47
months (range, 2-131 months). Twenty-eight patients (19%) experienced
locoregional failure, including 20 local failure, 5 regional failure and 3 with
both. Among the 24 patients who had image studies at recurrence, 15 patients had
in-field recurrence, 5 were marginal recurrence and 4 were out-field recurrence.
Seven patients (5%) had contralateral neck failure. Four of 5 patients with
marginal failure had recurrent tumors in the infratemporal fossa. In multivariate
analysis, extracapsular spread and positive or close surgical margin were
associated with poor locoregional control. CONCLUSION: Local in-field recurrence
is the most common failure pattern in lateralized buccogingival cancer after
postoperative RT. The infratemporal fossa is a risk area for marginal failure and
should be encompassed adequately in the postoperative RT field. Extracapsular
spread and positive or close margin are predictors of locoregional control for
lateralized oral cancer. Patients exhibiting such adverse features require more
aggressive treatment.
PMID- 28687158
TI - Reply.
PMID- 28687159
TI - 15 years of the histopathological synovitis score, further development and
review: A diagnostic score for rheumatology and orthopaedics.
AB - The histopathological synovitis score evaluates the immunological and
inflammatory changes of synovitis in a graduated manner generally customary for
diagnostic histopathological scores. The score results from semiquantitative
evaluation of the width of the synovial surface cell layer, the cell density of
the stroma and the density of the inflammatory infiltration into 4
semiquantitative levels (normal 0, mild 1, moderate 2, severe 3). The addition of
these values results in a final score of 0-9 out of 9. On the basis of this
summation the condition is divided into low-grade synovitis and high-grade
synovitis: A synovitis score of 1 to<=4 is called low-grade synovitis (arthrosis
associated/OA synovitis, posttraumatic synovitis, meniscopathy-associated
synovitis and synovitis with haemochromatosis). A synovitis score of>=5 to 9 is
called high-grade synovitis (rheumatoid arthritis, psoriatic arthritis, Lyme
arthritis, postinfection/reactive arthritis and peripheral arthritis with
Bechterew's disease). By means of the synovitis score it is therefore possible to
distinguish between degenerative/posttraumatic diseases (low-grade synovitis) and
inflammatory rheumatic diseases (high-grade synovitis) with a sensitivity of
61.7% and a specificity of 96.1%. The diagnostic accuracy according to ROC
analysis (AUC: 0.8-0.9) is good. Since the first publication (2002) and an
associated subsequent publication (2006), the synovitis score has nationally and
internationally been accepted for histopathological assessment of the synovitis.
In a PubMed data analysis (status: 14.02.2017), the following citation rates
according to Cited by PubMed Central articles resulted for the two synovitis
score publications: For DOI: 10.1078/0344-0338-5710261 there were 29 Cited by
PubMed Central articles and for the second extended publication
DOI:10.1111/j.1365-2559.2006.02508 there were 44 Cited by PubMed Central
articles. Therefore a total of 73 PubMed citations are observed over a period of
15 years, which demonstrates an international acceptance of the score. This
synovitis score provides for the first time a diagnostic, standardised and
reproducible histopathological evaluation method enabling a contribution to the
differential diagnosis of chronic inflammatory general joint diseases. This is
particularly the case by incorporation into the joint pathology algorithm. To
specify the synovitis score an immunohistochemical determination of various
inflammation-relevant CD antigens is proposed to enable a risk stratification of
high-grade synovitis (e.g.: progression risk and sensitivity for biologicals).
PMID- 28687160
TI - Prognostic value of putative cancer stem cell markers (CD24, CD44, CD133, and
ALDH1) in human papillary thyroid carcinoma.
AB - We hypothesized that cancer stem cells (CSCs) are responsible for the poor
outcome and aggressive clinicopathological factors. We surveyed the expression of
selected CSC markers that are specifically expressed in thyroid papillary
carcinoma (PTC). A total of 80 patients with PTC from 2011 to 2012 were enrolled.
We selected CD24, CD44, CD133, and dehydrogenase 1 (ALDH1), as they have been
suggested to be candidate CSC markers. Expression of these markers was
investigated by immunohistochemical (IHC) staining. IHC staining for CD24, CD44,
CD133 and ALDH1 was evaluated according to staining intensity and proportion. The
intensity and proportion scores were multiplied together for a total score, which
was either 0-2 (negative) or 3-7 (positive). IHC for CD133 in PTC was positive in
49 (61.3%) patients, and CD24 was positive in 28 (35.0%). Seventy-eight (97.5%)
patients were CD44 positive and 79 (98.8%) were ALDH1 positive. When we assessed
the relationship between CSC markers and clinicopathological factors in PTC, CD24
expression was inversely correlated with multifocality (p=0.045; odds ratio [OR],
0.370; 95% confidence interval [CI], 0.138-0.991) and CD44 expression was
significantly correlated with a BRAF mutation (p=0.001; OR, 7.091; 95% CI, 4.101
12.262). However, CD133 and ALDH1 were not associated with any of the
clinicopathological parameters. CD24 expression was inversely correlated with
multifocality, and CD44 expression was significantly correlated with a BRAF
mutation. Therefore, CD24 and CD44 are related to clinicopathological aggressive
features and important for determining surgical extent in patients with PTC.
PMID- 28687161
TI - Deregulation of miR-126-3p in basal-like breast cancers stroma and its clinical
significance.
AB - INTRODUCTION: The aim of this study was to investigate miR-126-3p expression in
stroma and tumor cells of basal-like breast cancer tissues, in an effort to
elucidate the potential effect of miR-126-3p on tumor microenvironment and
progress of basal-like breast cancer. METHODS: Expression levels of miR-126-3p in
33 paired basal-like breast cancer tissues were assayed by real-time quantitative
PCR. Tumor cells and normal epithelial cell were isolated from ten paired basal
like breast cancer tissues and matched adjacent tissues, separately, using laser
capture microdissect(LCM)-based PCR method. Further validated in larger sets were
assayed by tissue microarrays (TMA)-based ISH method. RESULTS: MiR-126-3p
expression level had no significant differences between basal-like breast cancer
subtypes and matched adjacent tissues. However, a decreasing trend of miR-126-3p
expression can be found in tumor cells of basal-like subtype, compared with
matched adjacent tissues, using LCM-based PCR. Using TMA method, miR-126-3p
expression level was the lowest in stroma of basal-like breast cancers among four
subtypes (chi2=10.55, P=0.01), and was increasing in stroma of breast cancers
compared with fibroadenomas. Furthermore, strong miR-126-3p expression in stroma
is significantly associated with HER-2 expression (chi2=4.70, P=0.03) and Ki-67
index. (chi2=4.84, P=0.03), which suggested a potential prognostic value of miR
126-3p in stroma of breast cancer. However, miR-126-3p expression in tumor cells
derived from different subtypes hadn't significant clinical values in this study.
CONCLUSIONS: the miR-126-3p expression level in breast cancer stroma was
associated with different intrinsic subtypes and its correlation with hormone
receptor and Ki-67 index shed light on the potential clinical prognostic value of
miR-126-3p, in the field of specific breast cancer subtypes.
PMID- 28687162
TI - Altered expression of lysosomal associated membrane protein 1 in esophageal
squamous cell carcinoma.
AB - BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is one of the most common
cancers. LAMP1, major protein components of lysosome, is primarily located on the
lysosomal membrane and rarely expressed on the surface of normal cells, playing
an important role in the lysosome-mediated physiological processes. Previous
studies confirmed that LAMP1 showed high expression in astrocytoma. The purpose
of this study was to investigate the expression levels of LAMP1 and to discuss
its roles in ESCC. METHODS: We collected 610 tissue samples of ESCC patients to
construct tissue microarrays, which were subsequently stained by
immunohistochemistry with LAMP1 antibody. RESULTS: After immunohistochemical
staining, a total of 584 patients, including 453 men and 131 women, were
analysed. The positive immunostaining was mainly located at the cytoplasm. The
LAMP1 expression levels were significantly different between different T status
(P<0.001), TNM stages (P<0.01) and degrees of tumor histological differentiation
(P<0.001). Besides, LAMP1 expression levels were positively correlated with TNM
stages (P<0.05). The higher the TNM stages, the higher the LAMP1 expression
levels. Similar results also appeared in degrees of tumor histological
differentiation (P<0.01), but not in ages, genders, tumor size, T status,
lymphatic metastasis and tumor locations (P>0.05). CONCLUSION: LAMP1 is involved
in the TNM stages and histological differentiation of the ESCC. Targeted therapy
for LAMP1 may be a promising novel therapeutic strategy against poorly
differentiated ESCC.
PMID- 28687163
TI - [Latent autoimmune diabetes in adults and ketoacidosis: A clinical case].
PMID- 28687164
TI - Very long evolution skin injuries.
PMID- 28687165
TI - Crimean-Congo Hemorrhagic Fever: A bibliometric assessment of the literature.
PMID- 28687166
TI - Re: The accuracy of emergency abdominal CT in adult patients who present with non
traumatic abdominal pain: results of a UK national audit.
PMID- 28687167
TI - Maximum intensity breast diffusion MRI for BI-RADS 4 lesions detected on X-ray
mammography.
AB - AIM: To investigate an abbreviated, contrast-agent free diffusion-weighted (DW)
breast magnetic resonance imaging (MRI) protocol that provides a single image for
the radiologist to read in order to non-invasively examine Breast Imaging
Reporting and Data System (BI-RADS) 4 lesions detected using breast cancer
screening X-ray mammography. MATERIALS AND METHODS: This retrospective evaluation
within a institutional review board-approved, prospective study included 115
women (mean 57 years, range 50-69 years) with BI-RADS 4 findings on X-ray
mammography and indication for biopsy over a period of 15 months. Full diagnostic
breast MRI (FDP) was performed prior to biopsy (1.5 T). Maximum intensity breast
diffusion (MIBD) images were generated from DW images (b = 1,500 mm/s2, 3 mm
section thickness) of the breast. MIBD and T2-weighted (T2W) images were read by
two radiologists and compared to the diagnostic accuracy of an expert reading of
the FDP with histopathology as the reference standard. The acquisition time of
MIBD and T2W MRI was about 7 minutes. RESULTS: MIBD MRI provided a diagnostic
accuracy of 87.93% (95% confidence interval [CI]: 80.58-93.24%) for R1 and 89.66%
(95% CI: 82.63-94.54%) for R2. Expert reading of the FDP revealed a similar
accuracy of 86.2% (95% CI: 78.67-91.43%). The positive predictive value (PPV)
could be increased from 36.2% (95% CI: 28.02-45.28; X-ray mammography alone) to a
mean PPV of 80.89% (R1 79.17%, R2 82.16%) using MIBD MRI. Mean reading time was
30 seconds (25%/75 percentile 24.5-41.25). CONCLUSIONS: MIBD MRI might be of
supplemental value if added to the work-up of BI-RADS 4 X-ray mammography
screening findings. MIBD MRI might help reduce the false-positive rate prior to
biopsy for reference lesions at only limited expense of measurement and reading
time.
PMID- 28687168
TI - Evidence-based anatomical review areas derived from systematic analysis of cases
from a radiological departmental discrepancy meeting.
AB - AIM: To produce short checklists of specific anatomical review sites for
different regions of the body based on the frequency of radiological errors
reviewed at radiology discrepancy meetings, thereby creating "evidence-based"
review areas for radiology reporting. MATERIALS AND METHODS: A single centre
discrepancy database was retrospectively reviewed from a 5-year period. All
errors were classified by type, modality, body system, and specific anatomical
location. Errors were assigned to one of four body regions: chest,
abdominopelvic, central nervous system (CNS), and musculoskeletal (MSK).
Frequencies of errors in anatomical locations were then analysed. RESULTS: There
were 561 errors in 477 examinations; 290 (46%) errors occurred in the
abdomen/pelvis, 99 (15.7%) in the chest, 117 (18.5%) in the CNS, and 125 (19.9%)
in the MSK system. In each body system, the five most common location were chest:
lung bases on computed tomography (CT), apices on radiography, pulmonary
vasculature, bones, and mediastinum; abdominopelvic: vasculature, colon, kidneys,
liver, and pancreas; CNS: intracranial vasculature, peripheral cerebral grey
matter, bone, parafalcine, and the frontotemporal lobes surrounding the Sylvian
fissure; and MSK: calvarium, sacrum, pelvis, chest, and spine. CONCLUSION: The
five listed locations accounted for >50% of all perceptual errors suggesting an
avenue for focused review at the end of reporting.
PMID- 28687169
TI - Pitfalls in diagnosing colon cancer on abdominal CT.
AB - AIM: To assess the frequency of undetected colon cancer on conventional abdominal
CT and to evaluate the imaging features that are characteristic of those cancers.
MATERIALS AND METHODS: The present study included consecutive patients diagnosed
with colorectal cancer at colonoscopy (2006-2015) who also underwent abdominal
computed tomography (CT) performed for various reasons within a year prior to the
colonoscopy. The frequency of undetected lesions was evaluated for the original
CT interpretations ("original readers"). Two radiologists ("study readers"),
blinded to the tumour location, independently performed interpretations oriented
for colon cancer detection. The study readers analysed the imaging features of
detected tumours (tumour shape, length, maximal wall thickness, free fluid, fat
stranding, vascular engorgement, stenosis, and lymphadenopathy). Imaging features
of the cancers undetected by the original readers were evaluated. RESULTS: The
study included 127 patients. The original readers' frequency of undetected cancer
was 25/127 (19.7%). Each study reader could not identify the cancer in 8/127
(6.3%) patients. Imaging features associated with undetected cancers by the
original readers included the absence of fat stranding (p=0.007, p=0.003),
absence of vascular engorgement (p<0.0001, p<0.0001) and absence of
lymphadenopathy (p=0.005, p=0.004). Undetected tumours were shorter than those
detected (original reader: 33.2+/-11.9 versus 51.4+/-18.2 mm; study reader:
32.5+/-9.6 versus 61.3+/-23.4 mm; p<0.001). CONCLUSION: Colon cancer is
undetected in 20% of abdominal CT examinations in patients subsequently proven to
have colon cancer at colonoscopy. The absence of fat stranding, vascular
engorgement, or lymphadenopathy, and an average tumour length of 3.3 cm are
contributing factors for failure of detection. Radiologists' training should
emphasis these findings as it may improve cancer detection, and clinicians should
be aware of the limitations of abdominal CT.
PMID- 28687171
TI - Volume-controlled versus short drainage after inguinofemoral lymphadenectomy in
vulvar cancer patients: A Dutch nationwide prospective study.
AB - OBJECTIVE: Inguinofemoral lymphadenectomy for patients with vulvar squamous cell
carcinoma is associated with a high incidence of postoperative wound
complications, which may be influenced by inguinal drain management. The aim of
this nationwide prospective study (MAMBO: Morbidity And Measurement of the BOdy)
was to assess the feasibility and the incidence of complications after volume
controlled versus short drainage. METHODS: The MAMBO study consisted of two
observational studies in all eight oncology centers in the Netherlands, conducted
between 2012 and 2016. In the first study, the drain was removed when the
production was <30ml/24h, except in the first 48h, and after a maximum of 28days
(MAMBO-IA). In the second study, the drain was removed five days postoperatively
regardless of production (MAMBO-IB). We assessed the complications within eight
weeks after surgery using logistic regression to compare the incidence of one or
more complications between the two drainage protocols, adjusting for possible
confounders. RESULTS: We included 77 patients (139 groins) for volume-controlled
drainage and 64 patients (112 groins) for short drainage. Volume-controlled
drainage was associated with significant less lymphocele formation. Moreover, we
found no difference in wound infection or primary wound breakdown. The estimated
incidence of one or more complications was 46% per groin after volume-controlled
drainage versus 75% after short drainage, (RD 29% (95% CI 8, 49) p=0.006).
CONCLUSIONS: This prospective study shows that volume-controlled drainage is
associated with significantly less complications compared to short drainage. We
therefore recommend volume-controlled drainage after inguinofemoral
lymphadenectomy in patients with vulvar squamous cell carcinoma.
PMID- 28687172
TI - Genetic variation of 20 autosomal STR loci in three ethnic groups (Zhuang, Dai
and Hani) in the Yunnan province of southwestern China.
PMID- 28687173
TI - How do geometry-related parameters influence the clinical performance of
orthodontic mini-implants? A systematic review and meta-analysis.
AB - The aim of this systematic review and meta-analysis was to investigate how
parameters related to geometry influence the clinical performance of orthodontic
mini-implants (MIs). Systematic searches were performed in electronic databases
including MEDLINE, Scopus, Web of Science, Virtual Health Library, and Cochrane
Library and reference lists up to March 2016. Eligibility criteria comprised
clinical studies involving patients who received MIs for orthodontic anchorage,
with data for categories of MI dimension, shape, and thread design and insertion
site, and evaluated by assessment of primary and secondary stability. Study
selection, data extraction, quality assessment, and a meta-analysis were carried
out. Twenty-seven studies were included in the qualitative synthesis: five
randomized, eight prospective, and 14 retrospective clinical studies. One study
with a serious risk of bias was later excluded. Medium and short MIs (1.4-1.9mm
diameter and 5-8mm length) presented the highest success rates (0.87, 95% CI 0.80
0.92). A maximum insertion torque of 13.28Ncm (standard error 0.34) was observed
for tapered self-drilling MIs in the mandible, whereas cylindrical MIs in the
maxilla presented a maximum removal torque of 10.01Ncm (standard error 0.17).
Moderate evidence indicates that the clinical performance of MIs is influenced by
implant geometry parameters and is also related to properties of the insertion
site. However, further research is necessary to support these associations.
PMID- 28687174
TI - Pre-implantation HLA matching: The production of a Saviour Child.
AB - Pre-implantation genetic diagnosis (PGD) requires the use of assisted
reproductive technology (ART) to create several pre-implantation-stage embryos,
followed by biopsy of embryonic cells for genetic testing and transfer of
selected embryos to the womb to establish a pregnancy. HLA typing of ART-created
embryos was first reported in 2001. The aim is to establish a pregnancy that is
HLA-compatible with an affected sibling who requires haematopoietic stem cell
transplantation. HLA-typing can be performed with or without PGD for the
exclusion of a single-gene disorder. Haematopoietic stem cells collected from the
umbilical cord blood or the bone marrow of the HLA-matched donor sibling born, or
a combination of both sources, are used for transplantation and cure of the
affected sibling. The procedure is multistep and technically challenging. All
specialists involved must aim to adequately support and counsel prospective
parents. Results have so far been encouraging, with many documented positive
outcomes of affected children being cured.
PMID- 28687175
TI - A comprehensive approach to managing threats of violence on a university or
college campus.
AB - Horrifying, high profile acts of violence on campuses remain relatively rare,
nevertheless, academic administrators are required to manage threats of violence
on campus on an increasingly regular basis. These threats take two primary forms,
those in which the perpetrator and the intended victim(s) are clearly identified,
often involving repeated threats and threatening behaviour towards an individual;
and those involving anonymous threats to commit acts of larger scale violence.
Complicating factors in managing these threats include: fear contagion; mass
media and social media attention; responsibilities to all members of the
university community sometimes including individuals issuing the threat and the
intended victims; demands for safety and security measures that are often at odds
with professional advice; and permeable campus boundaries that cause security
challenges. This paper considers the changing landscape of threat assessment and
risk assessment on university and college campuses and suggests opportunities for
partnerships between forensic mental health professionals and academic
administrators.
PMID- 28687176
TI - The impact of a single bout of high intensity circuit training on myokines'
concentrations and cognitive functions in women of different age.
AB - The study aimed to assess effect of a single bout of high-intensity circuit
training (HICT) on myokines concentration: interleukin-6 and irisin, inteleukin
10, brain-derived neurotrophic factor (BDNF), heat shock proteins (HSP27, HSP70)
and cognitive functions among women participated in HICT. It also attempted
evaluating whether vitamin D could have modified the effect of HICT. Fourteen
healthy, non-active women participating in the experiment were assigned to a
young or middle-aged group. They performed a single session HICT using body
weight as a resistance, based on the ACSM recommendations. Blood samples were
taken before, one and 24h after training. Cognitive functions were assessed
before and 1h after the HICT session. Simple statistics and effects of changes
for dependent variables were determined using mixed linear modeling, and
evaluated by means of magnitude-based inference (MBI). Following a single session
of HICT the young group exhibited improved concentration and spatial memory,
whereas in middle-aged women these functions were attenuated. A varied tendency
was also observed in the levels of myokine IL-6 and cytokine IL-10. Vitamin D was
covariate for changes in cognitive functions and myokines' levels after exercise.
Its concentration modified the anti-inflammatory effect of HICT, expressed in
decreasing HSP70.
PMID- 28687177
TI - Associative learning contributes to the increased water intake observed after
daily injections of angiotensin II.
AB - Daily injections of angiotensin II (AngII) cause a progressive increase of water
intake that resembles a classically ascribed non-associative sensitization.
Consistent with the presumption that the observed increase in intake was
sensitization, we hypothesized that it resulted from a pharmacological
interaction between AngII and its receptor. To test this hypothesis, and remove
the influence of drinking itself, we implemented a delay in water access after
injection of AngII (icv) on four consecutive 'induction days,' and then measured
intake on the next day ('test day') when rats were allowed to drink immediately
after AngII. The delay in water access effectively reduced water intake on the
four induction days, and rats with longer delays in access drank less on the test
day than did rats allowed to drink immediately after AngII on the induction days.
Additional experiments ruled out a role for a conditioned drinking response to
the injection alone, and demonstrated a lack of conditioned appetition after
pairing injections of AngII with water given by intragastric catheter. Taken
together, these findings suggest that the increased drinking observed after daily
injections of AngII is a conditioned appetition after repeated pairings of AngII
and water intake. We further conclude that repeated stimulation of the AngII
receptor alone is not sufficient to drive appetition.
PMID- 28687178
TI - A randomized pilot evaluation of individual-level abortion stigma resulting from
Pennsylvania mandated abortion counseling.
AB - OBJECTIVE: The objective was to investigate the effect of mandated abortion
counseling requirements intended to dissuade women from having abortions on
patients' individual-level abortion stigma. METHODS: We randomized women
presenting for abortion to complete a demographic survey and the validated
Individual Level Abortion Stigma (ILAS) scale either before (unexposed) or after
(exposed) hearing the mandatory Pennsylvania Abortion Control Act counseling via
a standardized video. A sample size of 46 (23 per group) allowed us to detect a 1
standard-deviation difference in mean ILAS score between the groups. The ILAS
scale ranges from 0 to 3.5, with higher scores indicating greater stigma.
RESULTS: From November 2015 to April 2016, 46 participants completed the study.
All baseline characteristics were balanced except that the unexposed group had a
greater proportion of low-income participants. The mean ILAS score among all
participants was 1.02+/-0.60. ILAS scores were significantly higher among the
unexposed group (median 1.25, interquartile range [IQR] 0.7-1.9) compared to the
exposed group (median 0.75, IQR 0.5-1.05; p=.016). However, when controlling for
participant income category, the effect of the mandated counseling on stigma
scores was no longer present (p=.068). CONCLUSIONS: In this randomized trial,
stigma scores were higher among women who had not heard the mandated abortion
counseling when compared with stigma scores for those who had heard the script,
but this effect was confounded by participants' income category. IMPLICATIONS:
Despite the small sample size in this pilot study, differences in stigma scores
for women exposed and unexposed to mandated counseling approached significance
even after controlling for income category. Women who heard the mandated
counseling had reduced stigma scores. A larger study is needed to better
characterize this effect. Further research is needed to understand how state
policies, counseling interactions and socioeconomic status are related to
abortion stigma.
PMID- 28687179
TI - Pressure dynamics in the non-gravid uterus: intrauterine pressure cannot confirm
tubal occlusion after non-surgical permanent contraception.
AB - OBJECTIVE: The objective was to determine if intrauterine pressure can
distinguish bilateral tubal occlusion (BTO) from unilateral or bilateral tubal
patency (TP) in women following a permanent contraception procedure. STUDY
DESIGN: We used a small inline pressure sensor to continuously monitor
intrauterine pressure during hysterosalpingogram (HSG) in a cross-sectional study
that enrolled women having HSGs for any indication. The primary outcome was the
peak intrauterine pressure compared between women with BTO and TP as verified by
HSG. RESULTS: We enrolled 150 subjects, of which 111 (74.0%) provided usable
pressure readings. Of these, 98/111 (88.3%) had TP, and 13 (11.7%) had BTO. There
was no difference in peak intrauterine pressure for subjects with TP (mean
293.8+/-58.7 mmHg) compared to those with BTO (292.7+/-71.3 mmHg, p=.95). Among
parous women, peak intrauterine pressure in subjects with BTO (311.9+/-78.0 mmHg)
was higher but not significantly different from subjects with TP (282.7+/-49.2
mmHg, p=.20). In linear regression analysis, peak intrauterine pressure was not
associated with age, body mass index, gravidity or having at least one prior live
birth. CONCLUSIONS: Measurement of peak intrauterine pressure does not
distinguish between women with patent and blocked fallopian tubes. This approach
would not be clinically useful to verify occlusion following permanent
contraception. IMPLICATIONS: Peak intrauterine pressure does not differ between
women with patent and occluded fallopian tubes and cannot be used to confirm
tubal occlusion after nonsurgical permanent contraception.
PMID- 28687180
TI - A patient with early myoclonic encephalopathy (EME) with a de novo KCNQ2
mutation.
AB - BACKGROUND: The potassium voltage-gated channel subfamily Q member 2 (KCNQ2) gene
has been reported to be associated with various types of epilepsy, including
benign familial neonatal seizure (BFNS), early infantile epileptic encephalopathy
(EIEE), and unclassified early onset encephalopathies. We herein report a patient
with early myoclonic encephalopathy (EME) caused by a KCNQ2 mutation. CASE
REPORT: A male infant started to exhibit erratic myoclonus several days after
birth and apnea attacks lasting for seconds with desaturation. One month after
birth, his myoclonuses worsened in frequency. Electroencephalogram (EEG) showed a
burst and suppression pattern, and myoclonuses occurred in the burst phase with
diffuse polyspikes on EEG. At five months, inter-ictal EEG revealed
hypsarrhythmia, but his attacks were still only myoclonuses. ACTH treatment was
effective and the myoclonus frequency markedly decreased. At one year of age,
whole-exome sequencing revealed a heterozygous mutation of the KCNQ2 gene
(NM_172107.2): c.601C>T; p.(Arg201Cys), which was confirmed as de novo by Sanger
sequencing. This mutation lies within the extracellular portion of the S4 voltage
sensor. CONCLUSION: Most patients with a KCNQ2 mutation present with seizures
starting in the neonatal period with varying severity, ranging from BFNS to
Ohtahara syndrome. Furthermore, KCNQ2 appears to be a causative gene for EME.
PMID- 28687181
TI - [Is there still an indication for the use of succinylcholine in cesarean section?
The answer is no].
PMID- 28687182
TI - Consistency of priorities for quality improvement for nursing homes in Italy and
Canada: A comparison of optimization models of resident satisfaction.
AB - The paper seeks to identify aspects of care that may be easily modified to yield
a desired level of improvement in residents' overall satisfaction with nursing
homes, comparing data across Canada and Italy. Using a structured questionnaire,
681 and 1116 nursing home residents were surveyed in Ontario in 2009 and in
Tuscany in 2012, respectively. Fourteen items were common to the surveys,
including willingness to recommend (WTR), which was used as the dependent
variable and measure of global satisfaction. The other analogous items were
entered as covariates in ordinal logistic regression models predicting residents'
WTR in each jurisdiction separately. Regression coefficients were then
incorporated into a constrained nonlinear optimization problem selecting the most
efficient combination of predictors necessary to increase WTR by as much as 15%.
Staff-related aspects of care were selected first in the optimization models of
each jurisdiction. In Ontario, to improve WTR the primary focus should be on
staff relationships with residents, while in Tuscany it was the technical skill
and knowledge of staff that was selected first by the optimization model.
Different optimization solutions might mean that the strategies required to
improve global satisfaction in one jurisdiction could be different than those for
the other jurisdictions. The optimization model employed provides a novel
solution for prioritizing areas of focus for quality improvement for nursing
homes.
PMID- 28687183
TI - New decision-making processes for the pricing of health technologies in Japan:
The FY 2016/2017 pilot phase for the introduction of economic evaluations.
AB - Economic evaluation is used for decision-making processes in healthcare
technologies in many developed countries. In Japan, no health economic data have
been requested for drugs, medical devices, and interventions till date. However,
economic evaluation is gradually gaining importance, and a trial implementation
of the cost-effectiveness evaluation of drugs and medical devices has begun.
Discussions on economic evaluation began in May 2012 within a newly established
sub-committee of the Chuikyo, referred to as the "Special Committee on Cost
Effectiveness." After four years of discussions, this committee determined that
during the trial implementation, the results of the cost-effectiveness evaluation
would be used for the re-pricing of drugs and medical devices at the end of
fiscal year (FY) 2017. Chuikyo selected 13 products (7 drugs and 6 medical
devices) as targets for this evaluation. These products will be evaluated until
the end of FY 2017 based on the following process: manufacturers will submit the
data of economic evaluation; the National Institute of Public Health will
coordinate the review process; academic groups will perform the actual review of
the submitted data, and the expert committee will appraise these data. This
represents the first step to introducing cost-effectiveness analysis in the
Japanese healthcare system. We believe that these efforts will contribute to the
efficiency and sustainability of the Japanese healthcare system.
PMID- 28687184
TI - Paraflocculus plays a role in salicylate-induced tinnitus.
AB - Tinnitus impairs quality of life of about 1-2% of the whole population. In most
severe situation, tinnitus may cause social isolation, depression and suicide.
Drug treatments for tinnitus are generally ineffective, and the mechanisms of
tinnitus are still undetermined. Accumulating evidence suggests that tinnitus is
related to changes of widespread brain networks. Recent studies propose that
paraflocculus (PFL), which is indirectly connected to various cortical regions,
may be a gating zone of tinnitus. So we examined the electrophysiological changes
and neurotransmitter alterations of the PFL in a rat model of sodium salicylate
(SS)-induced tinnitus. We found that spontaneous firing rate (SFR) of the
putative excitatory interneurons of the PFL was significantly increased. The
level of glutamic acid, which is the main excitatory neurotransmitter in the
nervous system, was also dramatically increased in the PFL after SS treatment.
These results confirmed the hyperactivity of PFL in the rats with SS-treatment,
which might be due to the increased glutamic acid. Then we examined the SFR of
the auditory cortex (AC), the center for auditory perception, before and after
electrical stimulation of the PFL. 71.4% (105/147) of the recorded neurons showed
a response to the stimulation of the PFL. The result demonstrated that
stimulation of the PFL could modulate the activity of the AC. Our study suggests
a role of PFL in SS-induced tinnitus and AC as a potential target of PFL in the
process of tinnitus.
PMID- 28687185
TI - Identifying hospital-onset Escherichia coli bacteraemia cases from English
mandatory surveillance: the case for applying a two-day post-admission rule.
AB - BACKGROUND: A national voluntary surveillance programme has shown year-on-year
increases in the number of bacteraemias caused by Escherichia coli. Mandatory
surveillance of E. coli bacteraemia was introduced in 2011 with the aim of
improving the quantity and quality of data collected. In contrast to the other
national mandatory surveillance programmes, cases are not currently categorized
based upon time of onset in relation to hospital admission. AIM: To assess the
case for applying time-of-onset categorization to cases of E. coli bacteraemia in
England. METHODS: Data for all cases of E. coli bacteraemia reported to Public
Health England between April 2012 and March 2016 were extracted from the national
mandatory surveillance database. Cases were categorized as hospital-onset if
positive blood cultures were obtained two or more days after admission. RESULTS:
Approximately 21% of cases were categorized as hospital-onset. However, the
proportion of hospital-onset cases decreased by 1% in each successive 12-month
period, from 23% in 2012/13 to 20% in 2015/16 (P<0.001). CONCLUSIONS:
Approximately one-fifth of E. coli bacteraemia cases reported via mandatory
surveillance were identified as hospital-onset. Given that prevention and control
strategies will vary by setting, the routine feedback of this information will
prove important in informing infection prevention and control efforts. The
categorization of this subset of cases represents an important step towards
better understanding of the epidemiology of E. coli bacteraemia.
PMID- 28687186
TI - Evaluation of a new packaging process for non-autoclavable endoscopes: results
for the first 100 microbiological samples.
AB - BACKGROUND: A new process for packaging endoscopes (SureStore(r), Medical
Innovations Group) immediately after they exit from washing and disinfection in
an automated endoscope reprocessor (AER) allows for endoscopes to be stored for
up to 15 days. AIM: To describe the microbiological quality of samples from
gastrointestinal endoscopes following this process. METHODS: Three-month
prospective study using microbiological sampling from a stock of 38
gastrointestinal endoscopes carried out in a French University Hospital. The
compliance rate (proportion of samples <=25 cfu with no pathogenic micro
organisms) and the rate of sterile samples (proportion of germ-free samples) were
calculated. We then used multivariate analysis to determine the factors
associated with the maintenance of sterility. FINDINGS: One hundred samples were
taken from stored endoscopes: 31 stored for <=3 days, 34 stored between 3 and 7
days, and 35 after storage between 7 and 15 days. The compliance rate was 98% and
the sterile sample rate was 60%. Only the time between leaving the AER and
packaging was significantly associated with the sterility of samples (P = 0.02).
The probability of having a sterile sample decreased 17-fold when the endoscope
was packaged >2 h after leaving the AER (P = 0.04) compared to an endoscope
packaged within 1 h after leaving the AER. CONCLUSION: The SureStore process
seems capable of satisfactorily maintaining compliance (98%) of samples taken
from endoscopes stored for up to 15 days. The delay in packaging should not
exceed 1 h, as the rate of sterile samples decreases thereafter.
PMID- 28687188
TI - [Oral and dental expression of thyroid diseases].
AB - Oral disorders were observed in children with congenital hypothyroidism, lately
apparent because of difficulties of feeding, swallowing disorders, and
macroglossia. Macroglossia was also a component of the severe acquired myxedema,
particularly observed in hypothyroidism related to autoimmune atrophic
thyroiditis beyond menopause. Lingual ectopy in children and adults could
determine respiratory gene or swallowing difficulties, and were detectable by
visual examination and the endobuccal touch. Expression of these events was
completely minimized since the neonatal screening of congenital hypothyroidism,
also by the common practice in adults of serum TSH determinations. Congenital and
acquired hormonal deficits are now early detected and correct with suppletive
doses of levothyroxine. Oral expression of hyperthyroidism is poor, even if
thyrotoxicosis is sometimes revealed by increased thirst. Caution is required for
dental care, mainly due to changes in the hemostatic functions. Finally, a
genetic predisposition to the medullary thyroid cancer may be revealed by an oral
and neuromatosis. Radioisotopic therapy of thyroid cancers is likely to alter the
salivation.
PMID- 28687189
TI - Regulatory effect of Fe-EDTA on mixotrophic cultivation of Chlorella sp. towards
biomass growth and metabolite production.
AB - The study examined the effect of varying concentrations of iron in the form of
ethylene diamine tetra-acetic acid ferric sodium salt (Fe-EDTA) for cultivation
of Chlorella sp. under mixotrophic condition to evaluate biomass growth and
metabolites production. The experimental data depicted enhanced biomass
production along with lipids, carbohydrates and proteins at an optimal iron
concentration (8mg/L). Relatively higher biomass production (5.4g/L; 96h) with
simultaneous total chlorophyll (5mg/mL (Chl a/b: 3.7/1.3mg/mL)), carbohydrates
(105mg/g) and proteins (593mg/g) was observed with 8 mg/L Fe-EDTA. Total and
neutral lipid content of 38% and 15.6% was observed under nutrient deprived
conditions. The presence of iron showed distinct influence on the saturated
fraction of FAME and increment in oleic acid (omega fatty acids; edible oil).
Higher concentrations of Fe-EDTA (10/12mg/L) depicted incremental fraction of
oleic acid.
PMID- 28687187
TI - Naloxone for heroin, prescription opioid, and illicitly made fentanyl overdoses:
Challenges and innovations responding to a dynamic epidemic.
AB - Community-based overdose prevention programs first emerged in the 1990's and are
now the leading public health intervention for overdose. Key elements of these
programs are overdose education and naloxone distribution to people who use
opioids and their social networks. We review the evolution of naloxone
programming through the heroin overdose era of the 1990's, the prescription
opioid era of the 2000's, and the current overdose crisis stemming from the
synthetic opioid era of illicitly manufactured fentanyl and its analogues in the
2010's. We present current challenges arising in this new era of synthetic
opioids, including variable potency of illicit drugs due to erratic adulteration
of the drug supply with synthetic opioids, potentially changing efficacy of
standard naloxone formulations for overdose rescue, potentially shorter overdose
response time, and reports of fentanyl exposure among people who use drugs but
are opioid naive. Future directions for adapting naloxone programming to the
dynamic opioid epidemic are proposed, including scale-up to new venues and social
networks, new standards for post-overdose care, expansion of supervised drug
consumption services, and integration of novel technologies to detect overdose
and deliver naloxone.
PMID- 28687190
TI - A synthetic BMP-2 mimicking peptide induces glioblastoma stem cell
differentiation.
AB - BACKGROUND: Glioblastoma (GBM) is the most aggressive type of primary brain
tumor, characterized by the intrinsic resistance to chemotherapy due to the
presence of a highly aggressive Cancer Stem Cell (CSC) sub-population. In this
context, Bone Morphogenetic Proteins (BMPs) have been demonstrated to induce CSC
differentiation and to sensitize GBM cells to treatments. METHODS: The BMP-2
mimicking peptide, named GBMP1a, was synthesized on solid-phase by Fmoc
chemistry. Structural characterization and prediction of receptor binding were
obtained by Circular Dicroism (CD) and NRM analyses. Activation of BMP signalling
was evaluated by a luciferase reporter assay and western blot. Pro
differentiating effects of GBMP1a were verified by immunostaining and neurosphere
assay in primary glioblastoma cultures. RESULTS: CD and NMR showed that GBMP1a
correctly folds into expected tridimensional structures and predicted its binding
to BMPR-IA to the same epitope as in the native complex. Reporter analysis
disclosed that GBMP1a is able to activate BMP signalling in GBM cells. Moreover,
BMP-signalling activation was specifically dependent on smad1/5/8
phosphorylation. Finally, we confirmed that GBMP1a treatment is sufficient to
enhance osteogenic differentiation of Mesenchymal Stem Cells and to induce
astroglial differentiation of glioma stem cells (GSCs) in vitro. CONCLUSIONS:
GBMP1a was demonstrated to be a good inducer of GSC differentiation, thus being
considered a potential anti-cancer tool to be further developed for GBM
treatment. GENERAL SIGNIFICANCE: These data highlight the role of BMP-mimicking
peptides as potential anti-cancer agents against GBM and stimulate the further
development of GBMP1a-based structures in order to enhance its stability and
activity.
PMID- 28687191
TI - Single anterior portal: A better option for arthroscopic treatment of traumatic
anterior shoulder instability?
AB - OBJECTIVE: The aim of this study was to compare single and double anterior portal
techniques in the arthroscopic treatment of traumatic anterior shoulder
instability. METHODS: A total of 91 cases who underwent arthroscopic Bankart
repair for anterior shoulder instability were reviewed. The patients were divided
into 2 groups as Group 1 (47 male and 2 female; mean age: 25.8 +/- 6.8) for
arthroscopic single anterior portal approach and Group 2 (41 male and 1 female;
mean age: 25.4 +/- 6.6) for the classical anterior double portal approach. The
groups were compared for clinical scores, range of motion, analgesia requirement,
complications, duration of surgery, cost and learning curve according to a short
questionnaire completed by the relevant healthcare professionals. RESULTS: No
statistically significant difference was found between the 2 groups in terms of
pre-operative and post-operative Constant and Rowe Shoulder Scores, range of
motion and complications (p > 0.05). In Group 2 patients, the requirement for
post-operative analgesics was significantly higher (p < 0.001), whereas the
duration of surgery was statistically significantly shorter in Group 1 (p <
0.001). In the assessment of the questionnaire, it was seen that a single portal
anterior approach was preferred at a higher ratio (p = 0.035). The cost analysis
revealed that the cost was 5.7% less for patients with a single portal.
CONCLUSION: In the arthroscopic treatment of traumatic anterior shoulder
instability accompanied by a Bankart lesion, the anterior single portal technique
is as successful in terms of clinical results as the conventional double portal
approach. The single portal technique has advantages such as less postoperative
pain, a shorter surgical learning curve and lower costs. LEVEL OF EVIDENCE: Level
III, Therapeutic study.
PMID- 28687192
TI - Optimisation of reconstruction, volumetry and dosimetry for 99mTc-SPECT and 90Y
PET images: Towards reliable dose-volume histograms for selective internal
radiation therapy with 90Y-microspheres.
AB - PURPOSE: In Selective Internal Radiation Therapy (SIRT), 99mTc-MAA SPECT images
are commonly used to predict microspheres distribution but recent works used 90Y
microspheres PET images. Nevertheless, evaluation of the predictive power of
99mTc-MAA has been hampered by the lack of reliable comparisons between 99mTc
SPECT and 90Y-PET images. Our aim was to determine the "in situ" optimisation
procedure in order to reliably compare 99mTc-SPECT and 90Y-PET images and achieve
optimal personal dosimetry. METHODS: We acquired 99mTc-SPECT/CT and 90Y-PET/CT
images of NEMA and Jaszczak phantoms. We found the best reconstruction parameters
for quantification and for volume estimations. We determined adaptive threshold
curves on the volumetric reconstruction. We copied the optimised volumes on the
quantitative reconstruction, named here the "cross volumes" technique. Finally,
we compared 99mTc-SPECT and 90Y-PET Dose Volume Histograms. RESULTS: Our "in
situ" optimisation procedure decreased errors on volumes and quantification (from
-44.2% and -15.8% to -3.4% and -3.28%, respectively, for the 26.5mL PET phantom
sphere). Moreover, 99mTc-SPECT and 90Y-PET DVHs were equivalent only after the
optimisation procedure (difference in mean dose <5% for the three biggest
spheres). CONCLUSIONS: This work showed that a preliminary "in situ" phantom
study was necessary to optimise volumes and quantification of 99mTc-SPECT and 90Y
PET images and allowed to achieve a reliable comparison between patient treatment
planning and post implant dosimetry, notably by the use of the "cross volumes"
technique. Methodology developed in this work will enable robust evaluations of
the predictive power of 99mTc-SPECT, as well as dose-response relationship and
side effects in SIRT treatments.
PMID- 28687170
TI - Erratum to "The histology of ovarian cancer: Worldwide distribution and
implications for international survival comparisons (CONCORD-2)" [Gynecol. Oncol.
144 (2017) 405-413].
PMID- 28687193
TI - [Prevention of anemia in blood donors].
AB - The prevention of anemia of blood donor is a main issue for donor safety and self
supplying. This prevention is done in one hand by donor deferral whose
haemoglobin level is under defined threshold and in other hand by preventing iron
deficiency. Some subgroups of donors are at increased risk for developing iron
deficiency and adverse effects of iron deficiency: premenopausal females; donors
with haemoglobin values near the minimum for eligibility and frequent donors.
Different interventions could be used: lengthening the inter-donational interval
and/or decreasing the number of donations per year; donor ferritin testing to
evaluate iron store and at least donor iron supplementation.
PMID- 28687194
TI - The influence of the commensal microbiota on distal tumor-promoting inflammation.
AB - Commensal microbes inhabit barrier surfaces, providing a first line of defense
against invading pathogens, aiding in metabolic function of the host, and playing
a vital role in immune development and function. Several recent studies have
demonstrated that commensal microbes influence systemic immune function and
homeostasis. For patients with extramucosal cancers, or cancers occurring distal
to barrier surfaces, the role of commensal microbes in influencing tumor
progression is beginning to be appreciated. Extrinsic factors such as chronic
inflammation, antibiotics, and chemotherapy dysregulate commensal homeostasis and
drive tumor-promoting systemic inflammation through a variety of mechanisms,
including disruption of barrier function and bacterial translocation, release of
soluble inflammatory mediators, and systemic changes in metabolic output.
Conversely, it has also been demonstrated that certain immune therapies,
immunogenic chemotherapies, and checkpoint inhibitors rely on the commensal
microbiota to facilitate anti-tumor immune responses. Thus, it is evident that
the mechanisms associated with commensal microbe facilitation of both pro- and
anti-tumor immune responses are context dependent and rely upon a variety of
factors present within the tumor microenvironment and systemic periphery. The
goal of this review is to highlight the various contexts during which commensal
microbes orchestrate systemic immune function with a focus on describing possible
scenarios where the loss of microbial homeostasis enhances tumor progression.
PMID- 28687195
TI - beta2-Microglobulin elicits itch-related responses in mice through the direct
activation of primary afferent neurons expressing transient receptor potential
vanilloid 1.
AB - Uremic pruritus is an unpleasant symptom in patients undergoing hemodialysis, and
the underlying mechanisms remain unclear. beta2-Microglobulin (beta2-MG) is well
known as an MHC class I molecule and its level is increased in the plasma of
patients undergoing hemodialysis. In this study, we investigated whether beta2-MG
was a pruritogen in mice. Intradermal injections of beta2-MG into the rostral
back induced scratching in a dose-dependent manner. Intradermal injection of
beta2-MG into the cheek also elicited scratching, but not wiping. beta2-MG
induced scratching was inhibited by the MU-opioid receptor antagonist naltrexone
hydrochloride. beta2-MG-induced scratching was not inhibited by antagonists of
itch-related receptors (e.g., H1 histamine receptor (terfenadine), TP thromboxane
receptor (DCHCH), BLT1 leukotriene B4 receptor (CMHVA), and proteinase-activated
receptor 2 (FSLLRY-NH2)). However, beta2-MG-induced scratching was attenuated in
mice desensitized by repeated application of capsaicin and also by a selective
transient receptor potential vanilloid 1 (TRPV1) antagonist (BCTC). In addition,
beta2-MG induced phosphorylation of extracellular signal-regulated kinase (a
marker of activated neurons) in primary culture of dorsal root ganglion neurons
that expressed TRPV1. These results suggest that beta2-MG is a pruritogen and
elicits itch-related responses, at least in part, through TRPV1-expressing
primary sensory neurons.
PMID- 28687196
TI - Protective effects of Forsythoside A on amyloid beta-induced apoptosis in PC12
cells by downregulating acetylcholinesterase.
AB - Increasing the acetylcholine level and fighting the neuroinflammation has always
been taken as a treatment strategy for Alzheimer's disease (AD). Forsythoside A
is a major component in Forsythia suspensa (Thunb.) Vahl (F. suspensa, Lianqiao
in Chinese) that has been traditionally used as Chinese herbal medicine to treat
the inflammation in China. This study examined the inhibitory
acetylcholinesterase activities of Forsythoside A at chemical and biological
level. Forsythoside A inhibited acetylcholinesterase in a mixed type of
inhibition, with Ki of 47.68MUM. Docking analysis strongly supported these
findings. In PC12 cells Forsythoside A increased cell viability and suppressed
acetylcholinesterase increased by Abeta25-35, thus alleviated the corresponding
apoptosis. Taken together, these results suggest that Forsythoside A has the
protective effects on Abeta25-35-induced apoptosis in PC12 cells by
downregulating acetylcholinesterase, making it a potential functional food
ingredient or drug candidate for the treatment of AD.
PMID- 28687197
TI - Opioid receptor activation is involved in neuroprotection induced by TRPV1
channel activation against excitotoxicity in the rat retina.
AB - Recently, we reported that capsaicin, a transient receptor potential vanilloid
type1 (TRPV1) agonist, protected against excitotoxicity induced by intravitreal N
methyl-D-aspartic acid (NMDA) in the rats in vivo. It has been reported that
morphine, an opioid receptor agonist, ameliorated excitotoxicity induced by
ischemia-reperfusion in the retina, and that capsaicin-induced neuroprotection
was reduced by naloxone, an opioid receptor antagonist in the brain. The aim of
the present study is to clarify whether activation of opioid receptors is
involved in the capsaicin-induced neuroprotection in the retina. Under
ketamine/xylazine anesthesia, male Sprague-Dawley rats were subjected to
intravitreal NMDA injection (200nmol/eye). Capsaicin (5.0nmol/eye), calcitonin
gene-related peptide (CGRP; 0.05pmol/eye), beta-endorphin (0.5 pmol/eye),
substance P (5nmol/eye), and naloxone (0.5nmol/eye) were intravitreally
administered simultaneously with NMDA. Morphometric evaluation 7 days after NMDA
injection showed that intravitreal NMDA injection resulted in ganglion cell loss.
Capsaicin, CGRP, beta-endorphin, and substance P prevented this damage. Treatment
with naloxone (0.5nmol/eye) almost completely negated the protective effects of
capsaicin, CGRP, beta-endorphin, and substance P in the NMDA-injected rats. These
results suggested that activation of opioid receptors is possibly involved in the
protective effect of capsaicin.
PMID- 28687198
TI - Neu-P11, a novel MT1/MT2 agonist, reverses diabetes by suppressing the
hypothalamic-pituitary-adrenal axis in rats.
AB - Excessive glucocorticoid (GC) in type 2 diabetes mellitus (T2DM) reduces insulin
sensitivity, impairs beta-cell function, increases gluconeogenesis and
glycogenolysis, impairs glucose uptake and metabolism, and reduces the
insulinotropic effects of glucagon-like peptide 1. Melatonin, which serves as a
physiological regulator of the hypothalamic-pituitary-adrenal (HPA) axis, has
been suggested to have anti-diabetic effects. The objective of the present study
was to investigate the effect of the MT1/MT2 melatonin agonist Neu-P11 on glucose
and lipid metabolism in T2DM rats induced by a high fat diet combined with low
doses of streptozotocin. T2DM rats were intragastrically administered melatonin
(20mg/kg), Neu-P11 (20, 10, 5mg/kg), or a vehicle for 4 weeks. The results showed
that the increased food intake, water consumption, hyperglycemia, glucose
intolerance, and insulin resistance in T2DM rats were all improved by Neu-P11
treatment. Neu-P11 increased GC receptor expression and suppressed 11beta
hydroxysteroid dehydrogenase 1 activity in the hippocampus by enhancing GC
sensitivity and HPA feedback, thus decreasing the high GC levels. Transcript
levels of the glucose metabolism-related genes peroxisome proliferator-activated
receptor-gamma, glucose transporter type-4, and adiponectin in adipose tissue
were significantly increased after Neu-P11 treatment, while leptin mRNA was
significantly decreased. Furthermore, MT1 and MT2 protein levels were enhanced by
Neu-P11. These data suggest that normalization of the hyperactivated HPA axis by
melatonin and Neu-P11 in T2DM regulates metabolic profiles and insulin
sensitivity, which may attenuate insulin resistance and glucose homeostasis.
Because Neu-P11 has superior pharmacokinetics and a longer half-life than
melatonin, it might be beneficial in treating obesity and T2DM.
PMID- 28687199
TI - Leveraging syntax to better capture the semantics of elliptical coordinated
compound noun phrases.
AB - Full-text scientific articles are increasingly available, but capturing the
meaning conveyed within an article automatically remains a bottleneck for
semantic search and reasoning systems. In this paper we consider elliptical
coordinated compound noun phrases that authors use to save space in an article.
Systems that do not attend to coordination would incorrectly interpret "breast or
lung cancer" as a body part (breast) and a disease (lung cancer) rather than two
diseases. The algorithmic approach introduced in this paper uses a generate-and
test strategy where candidate expansions for forward, backward and complex
ellipses are generated from syntactic dependencies. Dependencies are also used to
create a dictionary of non-coordinated noun phrases that is used during the test
phrase. Experiments on 21,280 full-text articles show that more than a million
noun phrases were impacted by coordinated ellipses. The system achieves 73.07%
precision, 75.38% recall, 74.23% F-score and 94.72% accuracy for new noun phrases
in the development set. The precision was higher for backward (82.62 vs. 78.63)
and forward expansions (64.82 vs. 60.17) and lower for complex expansions (63.41
vs. 72.59) in a test set. On average 10.79% of all noun phrases would be missed
if coordination were not resolved, which corresponds to 48 new noun phrases per
article in the journal Carcinogenesis, 52 new phrases per article in Diabetes,
and 56 new phrases per article in Endocrinology. Results also show coordinated
ellipses are more prevalent in abstracts (12.31% of all noun phrases) than in the
body of an article (10.70%). To further test the generalizability of this
approach the system (without modification) was used on two new collections.
PMID- 28687200
TI - Ceftriaxone reduces alcohol intake in outbred rats while upregulating xCT in the
nucleus accumbens core.
AB - Alcohol addiction is a chronic disease characterized by an inability to regulate
drinking. A critical brain region involved in alcohol consumption is the nucleus
accumbens (NA). Glutamate transmission in this region regulates alcohol
consumption and relapse to alcohol-seeking. Across multiple alcohol
administration rodent models, basal extracellular glutamate levels are increased
in the NA during early withdrawal. Glutamate transporter 1 (GLT-1) and system xC
, containing the subunit xCT, regulate NA glutamate levels. Ceftriaxone (Cef)
increases expression and function of both transporters following extinction from
cocaine self-administration and here we sought to determine if Cef would
similarly decrease alcohol consumption while increasing xCT and GLT-1 in the NA
core. We used the intermittent access to alcohol (IAA) paradigm to induce
drinking in outbred Sprague-Dawley rats; this paradigm permits rats access to
alcohol (20%v/v) for 24-h without water deprivation, followed by 24-h of
abstinence. Following 17 24-h drinking sessions, Cef treatment (200mg/kg IP) was
initiated and continued for 5days while a control group received vehicle (0.9%
saline IP). Alcohol consumption was assessed for two 24-h periods during Cef and
two 24-h periods after cessation of Cef treatment. In a separate cohort of rats,
Cef's ability to alter blood alcohol levels (BALs) after a non-contingent alcohol
injection (1g/kg) was assessed. We found that Cef decreased alcohol consumption
during the period of Cef treatment and on the two days following injections, and
this was accompanied by an increase in NA core xCT expression. Furthermore, a
history of alcohol consumption did not alter xCT and GLT-1 expression relative to
alcohol-naive controls. Cef did not alter BALs, indicating that the reduction in
alcohol consumption was not caused by altered alcohol clearance. These results
indicate that while Cef reduces alcohol consumption in outbred rats, its ability
to do so is not associated with an increase in GLT-1 expression.
PMID- 28687201
TI - Corrigendum to "A selective CB2R agonist (JWH133) restores neuronal circuit after
Germinal Matrix Hemorrhage in the preterm via CX3CR1+ microglia" [Neuropharm. 119
(2017) 157-169].
PMID- 28687202
TI - AuNP-CTG based probing system targeting CAG repeat DNA and RNA sequences.
AB - We have developed a AuNP-CTG based probing system that is applicable to the
detection of many units of CAG repeat sequences which was synthesized by a
rolling circle amplification (RCA) system with changes in fluorescence. We also
demonstrate that our AuNP-CTG based probing system could transfect without using
transfection reagent and detect target CAG repeat sequences in HeLa cells with
dramatic changes in fluorescence. This AuNP-CTG based probing system could also
be used, in conjunction with the CAG repeat RCA system, to detect target DNA.
This system was so sensitive to the target DNA that it could detect even
picomolar amounts with amplification of the fluorescence signal. Furthermore, we
have used our gold-based CAG probing system for the detection of RNA CAG repeat
sequences.
PMID- 28687203
TI - Macrocyclic inhibitors of Factor XIa: Discovery of alkyl-substituted macrocyclic
amide linkers with improved potency.
AB - Optimization of macrocyclic inhibitors of FXIa is described which focused on
modifications to both the macrocyclic linker and the P1 group. Increases in
potency were discovered through interactions with a key hydrophobic region near
the S1 prime pocket by substitution of the macrocyclic linker with small alkyl
groups. Both the position of substitution and the absolute stereochemistry of the
alkyl groups on the macrocyclic linker which led to improved potency varied
depending on the ring size of the macrocycle. Replacement of the
chlorophenyltetrazole cinnamide P1 in these optimized macrocycles reduced the
polar surface area and improved the oral bioavailability for the series, albeit
at the cost of a decrease in potency.
PMID- 28687204
TI - Optimization of 1H-indazol-3-amine derivatives as potent fibroblast growth factor
receptor inhibitors.
AB - Fibroblast growth factor receptor (FGFR) is a potential target for cancer therapy
because of its critical role in promoting cancer formation and progression. In a
continuing effort to improve the cellular activity of hit compound 7r bearing an
indazole scaffold, which was previously discovered by our group, several
compounds harnessing fluorine substituents were designed, synthesized and
biological evaluated. Besides, the region extended out to the ATP binding pocket
toward solvent was also explored. Among them, compound 2a containing 2,6-difluoro
3-methoxyphenyl residue exhibited the most potent activities (FGFR1: less than
4.1nM, FGFR2: 2.0+/-0.8nM). More importantly, compound 2a showed an improved
antiproliferative effect against KG1 cell lines and SNU16 cell lines with IC50
values of 25.3+/-4.6nM and 77.4+/-6.2nM respectively.
PMID- 28687205
TI - Oxindole-based intraocular pressure reducing agents.
AB - The study represents the new findings at the crossroads of chemistry and
medicine, particularly between medicinal and organic chemistry and ophthalmology.
In this work we describe how the chemical reactivity of indolinone scaffold may
be used to create small molecule ligands with strong biological response
comparable with and larger than that of endogenous hormone. The synthesis of
oxindole-based melatonin and 5-methoxycarbonylamino-N-acetyltryptamine (5-MCA
NAT) analogues was proposed and their ability to influence intraocular pressure
(IOP) was studied in vivo. Time-dependent study revealed the prolonged effect
(more than 6h) of the lead-compound. This effect in combination with high IOP
reducing effect (41+/-6%) in low concentrations of the active compound (0.1wt%)
and with high water solubility represents a great potential of low-cost oxindole
derivatives as potent antiglaucoma agents.
PMID- 28687206
TI - Diverse heterocyclic scaffolds as dCTP pyrophosphatase 1 inhibitors. Part 1:
Triazoles, triazolopyrimidines, triazinoindoles, quinoline hydrazones and
arylpiperazines.
AB - A high-throughput screening campaign using a commercial compound library
(ChemBridge DiverSET) revealed diverse chemotypes as inhibitors of the human dCTP
pyrophosphatase 1 (dCTPase). Triazole, triazolopyrimidine, triazinoindole,
quinoline hydrazone and arylpiperazine hits were clustered, confirmed by IC50
determinations, and their preliminary structure-activity-relationships (SAR) and
ligand efficiency scores are discussed in this letter.
PMID- 28687207
TI - High-risk of preterm birth and low birth weight after oocyte donation IVF:
analysis of 133,785 live births.
AB - A higher risk of pregnancy complications occurs after assisted reproductive
techniques compared with spontaneously conceived pregnancies. This is attributed
to the underlying infertility and assisted reproduction technique procedures
involved during treatment. It is a matter of interest whether use of donor
oocytes affects perinatal outcomes compared with pregnancies after autologous
IVF. Anonymized data were obtained from the Human Fertilization and Embryology
Authority. The analysis included 5929 oocyte donation and 127,856 autologous IVF
live births. Data from all women who underwent donor oocyte recipient or
autologous IVF cycles, both followed with fresh embryo transfer, were analysed to
compare perinatal outcomes of preterm birth (PTB) and low birthweight (LBW) after
singleton and multiple live births. The risk of adverse perinatal outcomes after
oocyte donation was increased: adjusted OR (aOR) 1.56, 99.5% CI 1.34 to 1.80 for
PTB and aOR 1.43, 99.5% CI 1.24 to 1.66 for LBW were significantly higher after
oocyte donation compared with autologous IVF singletons. The adjusted odds PTB
(aOR 1.21, 99.5% CI 1.02 to 1.43) was significantly higher after oocyte donation
compared with autologous IVF multiple births. Analysis of this large dataset
suggests significantly higher risk of PTB and LBW after ooctye donation compared
with autologous IVF pregnancies.
PMID- 28687208
TI - Assisted reproduction techniques in Latin America: the Latin American Registry,
2014.
AB - Multinational data on assisted reproduction techniques (IVF and intractytoplasmic
sperm injection [ICSI], frozen embryo transfer, oocyte donation, preimplantation
genetic diagnosis and fertility preservation) were collected from 159
institutions in 15 Latin American countries. A total of 41.34% of IVF-ICSI cycles
were conducted in women aged 35-39 years and 23.35% in women aged 40 years and
older. After removing freeze-all cases, delivery rate per oocyte retrieval was
25.05% for ICSI and 27.41% for IVF. Multiple births included 20.78% twins and
0.92% triplets and over. In oocyte donation, twins reached 28.93% and triplets
1.07%. Preterm deliveries reached 16.4% in singletons, 55.02% in twins and 76% in
triplets. Perinatal mortality in 18,162 births was 23 per 1000 in singletons, 35
per 1000 in twins, and 36 per 1000 in high-order multiples. Elective single
embryo transfer represented 2.63% of fresh transfers, with a 32.15% delivery rate
per transfer. Elective double embryo transfer represented 23.74% of transfers,
with a 41.03% delivery rate per transfer; 11,373 babies (62.6%) were singletons;
6398 (35.2%) twins, and 391 (2.2%), triplets and more. Given the effect of
multiple births on prematurity, morbidity and perinatal mortality, reinforcing
the existing trend of reducing the number of embryos transferred is mandatory.
PMID- 28687209
TI - New Sepsis and Septic Shock Definitions: Clinical Implications and Controversies.
AB - New sepsis definitions shift emphasis from the systemic inflammatory response
syndrome to organ dysfunction, quantified using the Sequential Organ Failure
Assessment (SOFA) score. The new definitions also propose Quick SOFA criteria to
rapidly identify potentially infected patients at risk for poor outcomes. The
diagnosis of septic shock requires vasopressor dependence and increased lactate
levels. Strengths of these definitions include their simplicity and clear
association with adverse outcomes. However, their utility in identifying patients
with serious infections before frank sepsis ensues remains to be seen. This
article reviews challenges in defining sepsis, strengths and weaknesses of the
new definitions, and unresolved issues.
PMID- 28687210
TI - Antimicrobial Stewardship Approaches in the Intensive Care Unit.
AB - Antimicrobial stewardship programs aim to monitor, improve, and measure
responsible antibiotic use. The intensive care unit (ICU), with its critically
ill patients and prevalence of multiple drug-resistant pathogens, presents unique
challenges. This article reviews approaches to stewardship with application to
the ICU, including the value of diagnostics, principles of empirical and
definitive therapy, and measures of effectiveness. There is good evidence that
antimicrobial stewardship results in more appropriate antimicrobial use, shorter
therapy durations, and lower resistance rates. Data demonstrating hard clinical
outcomes, such as adverse events and mortality, are more limited but encouraging;
further studies are needed.
PMID- 28687212
TI - Sepsis and Challenging Infections in the Immunosuppressed Patient in the
Intensive Care Unit.
AB - In 2017, most intensive care units (ICUs) worldwide are admitting a growing
population of immunosuppressed patients. The most common causes of pre-ICU
immunosuppression are solid organ transplantation, hematopoietic stem cell
transplantation, and infection due to human immunodeficiency virus. In this
article, the authors review the most frequent infections that cause critical care
illness in each of these 3 immunosuppressed patient populations.
PMID- 28687211
TI - Preventing Transmission of Multidrug-Resistant Pathogens in the Intensive Care
Unit.
AB - Infection control in the intensive care unit (ICU) has seen many advances,
including rapid molecular screening tests for resistant organisms and
chlorhexidine use in daily baths. Although these developments advance the cause
of infection prevention, compliance with some of the basic measures remains
elusive. Hand hygiene, antimicrobial stewardship, and reduction in device use
remain the low-technology interventions that could have a major impact on
nosocomial transmission of antimicrobial-resistant organisms. Although continued
research is needed on new and old ways of preventing nosocomial infections, ICU
staff must persevere in improving adherence with the measures that are known to
be effective.
PMID- 28687213
TI - Prevention of Central Line-Associated Bloodstream Infections.
AB - Central venous catheters (CVCs) are commonly used in critically ill patients and
offer several advantages to peripheral intravenous access. However, indwelling
CVCs have the potential to lead to bloodstream infections, with the risk
increasing with an array of characteristics, such as catheter choice, catheter
location, insertion technique, and catheter maintenance. Evidence-based
guidelines have led to a significant reduction in the incidence of bloodstream
infections associated with CVCs. The combination of guideline implementation and
newer technologies has the potential to further reduce morbidity and mortality
from infections related to CVCs.
PMID- 28687214
TI - Severe Respiratory Viral Infections: New Evidence and Changing Paradigms.
AB - Lower respiratory tract infection is a leading cause of death in the United
States. Advances in diagnostic testing have improved our ability to detect
pathogens. Viral pathogens are important causal pathogens in immunocompetent
patients. As the number of elderly adults and those with chronic medical
conditions increases, the burden of viral respiratory infections will increase.
Clinicians must be familiar with the characteristics of rhinovirus, human
adenoviruses, respiratory syncytial virus, and human metapneumovirus. Major
challenges include distinguishing true infection from asymptomatic carriage and
characterizing patients admitted with severe lower respiratory tract infection
who do not have a causative pathogen identified.
PMID- 28687215
TI - Invasive Fungal Infections in the Intensive Care Unit.
AB - Patients in the intensive care unit are exposed to multiple stressors that
predispose them to invasive fungal infections (IFIs), which carry high morbidity
and mortality. Getting acquainted with the diagnostic methods and therapies is
imperative for patient safety and for providing high-quality health care. This
article focuses on the most frequent IFIs: invasive candidiasis and invasive
aspergillosis.
PMID- 28687216
TI - Left ventricular volume measurements with free breathing respiratory self-gated 3
dimensional golden angle radial whole-heart cine imaging - Feasibility and
reproducibility.
AB - PURPOSE: To develop and evaluate a free breathing respiratory self-gated
isotropic resolution technique for left ventricular (LV) volume measurements.
METHODS: A 3D radial trajectory with double golden-angle ordering was used for
free-running data acquisition during free breathing in 9 healthy volunteers. A
respiratory self-gating signal was extracted from the center of k-space and used
with the electrocardiogram to bin all data into 3 respiratory and 25 cardiac
phases. 3D image volumes were reconstructed and the LV endocardial border was
segmented. LV volume measurements and reproducibility from 3D free breathing cine
were compared to conventional 2D breath-held cine. RESULTS: No difference was
found between 3D free breathing cine and 2D breath-held cine with regards to LV
ejection fraction, stroke volume, end-systolic volume and end-diastolic volume
(P<0.05 for all). The test-retest differences did not differ between 3D free
breathing cine and 2D breath-held cine (P<0.05 for all). CONCLUSION: 3D free
breathing cine and conventional 2D breath-held cine showed similar values and
test-retest repeatability for LV volumes in healthy volunteers. 3D free breathing
cine enabled retrospective sorting and arbitrary angulation of isotropic data,
and could correctly measure LV volumes during free breathing acquisition.
PMID- 28687217
TI - Using the "Stethoscope Test" to improve preoperative diagnosis for appendicitis
in children.
PMID- 28687218
TI - Keratoconus Screening Indices and Their Diagnostic Ability to Distinguish Normal
From Ectatic Corneas.
AB - PURPOSE: To compare the diagnostic ability of 3 Scheimpflug devices in
differentiating normal from ectatic corneas. DESIGN: Comparison of diagnostic
instrument accuracy. METHODS: This study included 42 normal, 37 subclinical
keratoconic, and 51 keratoconic eyes seen in a tertiary eye care institute.
Keratoconus screening indices were evaluated using the Pentacam (Oculus, Wetzlar,
Germany), Galilei (Ziemer, Biel, Switzerland), and Sirius (Costruzione Strumenti
Oftalmici, Florence, Italy). Sensitivity, specificity, and area under receiver
operating characteristic curve (AUC) were calculated. RESULTS: Highest
sensitivity (100%) to diagnose keratoconus was seen for 6 parameters on Pentacam
and 1 on Galilei. None of the indices in Sirius reached 100% sensitivity. For
subclinical keratoconus, the highest sensitivity (100%) was seen for 2 parameters
on Pentacam but for none of them on Galilei and Sirius. All parameters were
strong enough to differentiate keratoconus (AUC > 0.9). On comparing the best
parameters of all 3 machines, the AUC of the Belin/Ambrosio enhanced ectasia
total derivation (BAD-D) and the inferior-superior value (ISV) of Pentacam were
statistically similar to that of the keratoconus prediction index (KPI) and
keratoconus probability (Kprob) of Galilei (P = .27) and 4.5 mm root mean square
per unit area (RMS/A) back of Sirius (P = .55). When differentiating subclinical
from normal corneas, BAD-D was similar to the surface regularity index (SRI) of
Galilei (P = .78) but was significantly greater than the 8 mm RMS/A back of
Sirius (P = .002). CONCLUSION: Keratoconus indices measured by all 3 machines can
effectively differentiate keratoconus from normal corneas. However, new cutoff
values might be needed to differentiate subclinical from normal corneas.
PMID- 28687219
TI - Diabetic Macular Edema With and Without Subfoveal Neuroretinal Detachment: Two
Different Morphologic and Functional Entities.
AB - PURPOSE: To assess specific morphologic and functional characteristics in eyes
with diabetic macular edema (DME) with subfoveal neuroretinal detachment (SND+)
vs DME without SND (SND-). DESIGN: Cross-sectional, prospective, comparative case
series. METHODS: Seventy-two patients (72 eyes: 22 eyes SND+ and 50 eyes SND-)
with treatment-naive, center-involving DME were evaluated. Data gathering
included fundus color photographs, fluorescein angiography, spectral-domain
optical coherence tomography (SD-OCT), best-corrected visual acuity (BCVA), and
microperimetry. The following parameters were evaluated with SD-OCT: central
macular thickness (CMT [including SND]); central retinal thickness (CRT
[excluding SND]); choroidal thickness (CT); nasal and temporal retinal thickness
(RT) at 500 MUm and 1500 MUm from the fovea; the number of hyperreflective
retinal spots (HRS) in the central 3000 MUm; and the presence of SND and
integrity of the external limiting membrane (ELM). Retinal sensitivity (RS) was
evaluated within 4 degrees and 12 degrees of the fovea. Correlation among CT, RS,
and HRS in patients with and without SND was determined. RESULTS: CMT (P = .032),
temporal RT at 1500 MUm (P = .03), mean CT (P = .009), and mean number of HRS (P
= .0001) were all higher in SND+ vs SND- eyes. CRT, BCVA, HbA1c, and prevalence
of systemic arterial hypertension were not different between the 2 groups. RS
within 4 degrees (P = .002) and 12 degrees (P = .015) was lower in SND+ vs SND-
eyes. SND correlated significantly with disruption of the ELM (54.55% vs 24%, P =
.01) and lower RS. A direct correlation was found between the number of HRS,
presence of SND, CT, and RS within 12 degrees in SND- eyes, and an inverse
correlation was found between CT and RS within 12degrees in SND+ eyes.
CONCLUSIONS: These data may improve characterization of DME in eyes with SND. DME
with SND correlates with greater CT, more HRS, disruption of the ELM, and
significant macular functional impairment (RS decrease) vs SND-.
PMID- 28687220
TI - One- Versus Two-Muscle Surgery for Presumed Unilateral Fourth Nerve Palsy
Associated With Moderate Angle Hyperdeviations.
AB - PURPOSE: To compare 1-muscle vs 2-muscle surgery for moderate-angle
hyperdeviations owing to presumed unilateral fourth nerve palsy. DESIGN:
Retrospective chart review. METHODS: Seventy-three patients (aged 5-86 years)
underwent either 1- or 2-muscle surgery at our institution for moderate
hyperdeviation owing to presumed unilateral fourth nerve palsy, measuring 14-25
prism diopters (PD) in straight-ahead gaze at distance fixation. Six-week and 1
year motor success was defined as zero vertical deviation or 1-4 PD
undercorrection at distance, overcorrection as any reversal of hypertropia, and
undercorrection as >4 PD. Diplopia success was defined as no diplopia, or only
rarely for distance straight ahead and reading. RESULTS: Twenty-eight patients
underwent 1-muscle surgery, and 45 patients underwent 2-muscle surgery. Motor
success was similar (64% vs 67%, P > .99 at 6 weeks; 47% vs 55%, P = .8 at 1
year, n = 46), but there were more undercorrections at 6 weeks with 1-muscle
surgery (36% vs 16%, P = .09) and more overcorrections at 6 weeks with 2-muscle
surgery (0% vs 18%, P = .02). Diplopia success was also somewhat similar between
1- and 2-muscle surgery at 6 weeks (73% vs 60%, P = .5) and 1 year (45% vs 59%, P
= .5). CONCLUSION: For moderate-angle hyperdeviations owing to presumed
unilateral fourth nerve palsy, there appears no clear advantage of 2-muscle
surgery for motor outcomes. Diplopia success was similar between 1- and 2-muscle
surgery, owing to a greater number of less symptomatic undercorrections with 1
muscle surgery and a smaller number of more symptomatic overcorrections with 2
muscle surgery.
PMID- 28687221
TI - Low serum C-reactive protein levels predict 90-day mortality in hypoglycaemic
patients.
PMID- 28687222
TI - TP53 and IDH2 Somatic Mutations Are Associated With Inferior Overall Survival
After Allogeneic Hematopoietic Cell Transplantation for Myelodysplastic Syndrome.
AB - BACKGROUND: Next-generation sequencing has identified somatic mutations that are
prognostic of cancer. PATIENTS AND METHODS: We evaluated the incidence and
prognostic significance of somatic mutations in 89 myelodysplastic syndrome (MDS)
patients who received an allogeneic hematopoietic cell transplantation. Next
generation sequencing was performed on paraffin embedded bone marrow, which was
obtained at a median of 31 days before initiating the preparative regimen.
RESULTS: The 3 most common subtypes of MDS were refractory anemia with excess
blasts (RAEB)-1 (35%), RAEB-2 (29%), and refractory cytopenia with multilineage
dysplasia (18%). Most patients (91%) received a myeloablative regimen of
fludarabine with intravenous busulfan. Somatic mutations (> 0) were identified in
39 (44%) of analyzed samples. The 6 most commonly identified gene mutations were
ASXL1 (8%), DNMT3A (8%), RUNX1 (7%), KRAS (6%), IDH2 (4%), and TP53 (4%). The low
incidence of mutations in our study sample might be explained by tissue source
and stringent variant-calling methodology. Moreover, we speculate that the low
incidence of mutations might, perhaps, also be explained by previous azacitidine
treatment in 82% of cases. Multivariate analysis identified TP53 (hazard ratio
[HR], 3.82; 95% confidence interval [CI], 1.12-13.09; P = .03) and IDH2 mutations
(HR, 4.74; 95% CI, 1.33-16.91; P = .02) as predictors of inferior 3-year overall
survival. CONCLUSION: This study furthers implementation of clinical genomics in
MDS and identifies TP53 and IDH2 as targets for pre- or post-transplant therapy.
PMID- 28687223
TI - How to prevent relapse after allogeneic hematopoietic stem cell transplantation
in patients with acute leukemia and myelodysplastic syndrome.
AB - Disease relapse remains the first cause of mortality of hematological
malignancies after allogeneic hematopoietic stem cell transplantation (allo-HCT).
The risk of recurrence is elevated in acute myeloid leukemia (AML) patients with
high-risk cytogenetic or molecular abnormalities, as well as when allo-HCT is
performed in patients with refractory hematological malignancies or with
persistent molecular or radiological (PET-CT scan) residual disease. For high
risk AML and myelodysplasia (MDS), a post transplant maintenance strategy is
possible, using hypomethylating agents or tyrosine kinase inhibitors (TKI) anti
FLT3 when the target is present. For Philadelphia positive acute lymphoblastic
leukemia (ALL), there is a consensus for the use of TKI anti BCR-ABL as post
transplant maintenance.
PMID- 28687224
TI - Numerical simulation of colloidal self-assembly of super-hydrophobic arachnid
cerotegument structures.
AB - Certain arachnids exhibit complex coatings of their exoskeleton, consisting of
globular structures with complex surface features. This, so-called, cerotegument
is formed by a multi-component colloidal secretion that self-assembles and cures
on the body surface, and leads to high water repellency. Previous ultrastructural
studies revealed the involvement of different glandular cells that contribute
different components to the secretion mixture, but the overall process of self
assembly into the complex regular structures observed remained highly unclear.
Here we study this process from a theoretical point of view, starting from the so
called Tammes-problem. We show that slight changes of simple parameters lead to a
variety of morphologies that are highly similar to the ones observed in the
species specific cerotegument structures of whip-spiders. These results are not
only important for our understanding of the formation of globular hierarchical
structures in nature, but also for the fabrication of novel surface coatings by
colloidal lithography.
PMID- 28687227
TI - Chemical protein synthesis: Inventing synthetic methods to decipher how proteins
work.
AB - Total chemical synthesis of proteins has been rendered practical by the chemical
ligation principle: chemoselective condensation of unprotected peptide segments
equipped with unique, mutually reactive functional groups, enabled by formation
of a non-native replacement for the peptide bond. Ligation chemistries are
briefly described, including native chemical ligation - thioester-mediated, amide
forming reaction at Xaa-Cys sites - and its extensions. Case studies from the
author's own works are used to illustrate the utility and applications of
chemical protein synthesis. Selected recent developments in the field are briefly
discussed.
PMID- 28687226
TI - Acquired long QT syndrome and phosphoinositide 3-kinase.
AB - While it is well known that mutation of several different ion channels can cause
congenital long QT syndrome, block of IKr is widely thought to be responsible for
most cases of drug-induced acquired long QT syndrome (aLQTS). In this article, we
review evidence supporting another cause of aLQTS due to inhibition of
phosphoinositide 3-kinase (PI3K) signaling. Inhibition of PI3K affects multiple
plateau currents, reducing IKr, IKs, and ICaL while increasing the persistent
sodium current (INaP). The effects of PI3K inhibitors develop slowly, requiring
hours to days to reach steady state. Dofetilide and terfenadine, an antihistamine
on which much of the original IKr hypothesis was based, are among the many drugs
that inhibit the PI3K pathway. Reduced PI3K signaling may also play a role in
aLQTS associated with diabetes. Drug safety testing to identify aLQTS risk may be
improved by examining PI3K-dependent effects that develop over time.
PMID- 28687228
TI - Effect of replacing main-chain ureas with thiourea and guanidinium surrogates on
the bactericidal activity of membrane active oligourea foldamers.
AB - Membrane-active foldamers have recently emerged as potential mimics of
antimicrobial peptides (AMPs). Amphiphilic cationic helical N,N'-linked
oligoureas are one such class of AMP mimics with activities in vitro against a
broad range of bacteria including Bacillus anthracis, a Gram-positive sporulating
bacillus and causing agent of anthrax. Here we have used site-selective chemical
modifications of the oligourea backbone to gain additional insight into the
relationship between structure and function and modulate anthracidal activity. A
series of analogues in which urea linkages at selected positions are replaced by
thiourea and guanidium surrogates have been prepared on solid support and tested
against different bacterial forms of B. anthracis (germinated spores and
encapsulated bacilli). Urea->thiourea and urea->guanidinium replacements close to
the negative end of the helix dipole led to analogues with increased potency and
selectivity for B. anthracis versus mammalian cells.
PMID- 28687225
TI - Screening cleavage of Factor XIII V34X Activation Peptides by thrombin mutants: A
strategy for controlling fibrin architecture.
AB - In blood coagulation, thrombin converts fibrinogen into fibrin monomers that
polymerize into a clot network. Thrombin also activates Factor XIII by cleaving
the R37-G38 peptide bond of the Activation Peptide (AP) segment. The resultant
transglutaminase introduces covalent crosslinks into the fibrin clot. A strategy
to modify clot architecture would be to design FXIII AP sequences that are easier
or more difficult to be thrombin-cleaved thus controlling initiation of
crosslinking. To aid in this design process, FXIII V34X (28-41) Activation
Peptides were kinetically ranked for cleavage by wild-type thrombin and several
anticoagulant mutants. Thrombin-catalyzed hydrolysis of aromatic FXIII F34, W34,
and Y34 APs was compared with V34 and L34. Cardioprotective FXIII L34 remained
the variant most readily cleaved by wild-type thrombin. The potent anticoagulant
thrombins W215A and W215A/E217A (missing a key substrate platform for binding
fibrinogen) were best able to hydrolyze FXIII F34 and W34 APs. Thrombin I174A and
L99A could effectively accommodate FXIII W34 and Y34 APs yielding kinetic
parameters comparable to FXIII AP L34 with wild-type thrombin. None of the
aromatic FXIII V34X APs could be hydrolyzed by thrombin Y60aA. FXIII F34 and W34
are promising candidates for FXIII - anticoagulant thrombin systems that could
permit FXIII-catalyzed crosslinking in the presence of reduced fibrin formation.
By contrast, FXIII Y34 with thrombin (Y60aA or W215A/E217A) could help assure
that both fibrin clot formation and protein crosslinking are hindered. Regulating
the activation of FXIII is predicted to be a strategy for helping to control
fibrin clot architecture and its neighboring environments.
PMID- 28687229
TI - The phosphodiesterase 10A selective inhibitor, TAK-063, induces c-Fos expression
in both direct and indirect pathway medium spiny neurons and sub-regions of the
medial prefrontal cortex in rats.
AB - TAK-063, a selective phosphodiesterase 10A (PDE10A) inhibitor, produces potent
antipsychotic-like and pro-cognitive effects in rodents via balanced activation
of striatal direct and indirect pathway medium spiny neurons (MSNs). Brain
activity modulation by TAK-063 has been characterized using pharmacological
magnetic resonance imaging and electroencephalography in animals, revealing
modulation of activity in the prefrontal cortex (PFC) where there is little or no
PDE10A expression. To understand the specific brain regions and cells affected by
TAK-063 in rats, we assessed neural activation in the striatal complex and PFC
using immunofluorescence staining to measure c-Fos expression. TAK-063 at 0.3 and
3mg/kg induced a dose-dependent increase in the number of c-Fos immunoreactive
cells in the striatal complex. Furthermore, TAK-063 increased the number of MSNs
expressing c-fos mRNA in both the D1 receptor-expressing direct pathway and D2
receptor-expressing indirect pathway of the striatal complex. TAK-063 (0.3 and
3mg/kg) induced c-Fos expression in the anterior cingulate cortex (ACC) and
prelimbic cortex (PrL), but not the infralimbic, dorsal peduncular, primary motor
or anterior insular cortices. These findings suggest that administration of TAK
063 activates similar numbers of direct and indirect pathway MSNs, resulting in
activation predominantly in medial PFC sub-regions, such as the ACC and PrL.
PMID- 28687230
TI - Corrigendum to "Clinical Outcomes of Correcting Cervical Deformity in Cerebral
Palsy Patients" [World Neurosurgery 96 (2016) 500-509].
PMID- 28687231
TI - Mepolizumab efficacy in patients with severe eosinophilic asthma receiving
different controller therapies.
PMID- 28687232
TI - Reduced need for surgery in severe nasal polyposis with mepolizumab: Randomized
trial.
AB - BACKGROUND: Patients with eosinophilic nasal polyposis frequently require
surgery, and recurrence rates are high. OBJECTIVE: We sought to assess the
efficacy and safety of mepolizumab versus placebo for severe bilateral nasal
polyposis. METHODS: This randomized, double-blind, placebo-controlled trial
recruited patients aged 18 to 70 years with recurrent nasal polyposis requiring
surgery. Patients received 750 mg of intravenous mepolizumab or placebo every 4
weeks for a total of 6 doses in addition to daily topical corticosteroid
treatment. The primary end point was the number of patients no longer requiring
surgery at Week 25 based on a composite end point of endoscopic nasal polyp score
and nasal polyposis severity visual analog scale (VAS) score. Secondary end
points included change in nasal polyposis severity VAS score, endoscopic nasal
polyp score, improvement in individual VAS symptoms (rhinorrhea, mucus in throat,
nasal blockage, and sense of smell), patient-reported outcomes, and safety.
RESULTS: One hundred five patients received mepolizumab (n = 54) or placebo (n =
51). A significantly greater proportion of patients in the mepolizumab group
compared with the placebo group no longer required surgery at Week 25 (16 [30%]
vs 5 [10%], respectively; P = .006). There was a significant improvement in nasal
polyposis severity VAS score, endoscopic nasal polyp score, all individual VAS
symptom scores, and Sino-Nasal Outcome Test patient-reported outcome score in the
mepolizumab compared with placebo groups. Mepolizumab's safety profile was
comparable with that of placebo. CONCLUSION: In patients with recurrent nasal
polyposis receiving topical corticosteroids who required surgery, mepolizumab
treatment led to a greater reduction in the need for surgery and a greater
improvement in symptoms than placebo.
PMID- 28687233
TI - Overview of immune abnormalities in lysosomal storage disorders.
AB - The critical relevance of the lysosomal compartment for normal cellular function
can be proved by numbering the clinical phenotypes that arise in lysosomal
storage disorders (LSDs), a group of around 70 different monogenic autosomal or X
linked syndromes, caused by specific lysosomal enzyme deficiencies: all LSDs are
characterized by progressive accumulation of heterogeneous biologic materials in
the lysosomes of various parts of the body such as viscera, skeleton, skin,
heart, and central nervous system. At least a fraction of LSDs has been
associated with mixed abnormalities involving the immune system, while some
patients with LSDs may result more prone to autoimmune phenomena. A large
production of proinflammatory cytokines has been observed in Gaucher and Fabry
diseases, and wide different autoantibody production has been also reported in
both. Many immune-mediated reactions are crucial to the pathogenesis of different
inflammatory signs in mucopolysaccharidoses, and subverted heparan sulphate
catabolism might dysregulate cellular homeostasis in the brain of these patients.
Furthermore, an inappropriate activation of microglia is implicated in the
neurodegenerative foci of Niemann-Pick disease, in which abnormal signalling
pathways are activated by impaired sphingolipid metabolism. In addition, not the
simple impaired catabolism of gangliosides per se, but also the production of
anti-ganglioside autoantibodies contributes to the neurological disease of
gangliosidoses. Even if the exact relationship between the modification of
lysosomal activities and modulation of the immune system remains obscure, there
is emerging evidence of different impaired immunity responses in a variety of
LSDs: in this review we investigate and summarize the immune abnormalities and/or
clinical data about immune system irregularities which have been described in a
subset of LSDs.
PMID- 28687234
TI - Myeloid-derived suppressor cells modulate B-cell responses.
AB - Myeloid-derived suppressor cells (MDSCs) are key regulators of adaptive immunity
by suppressing T-cell functions. However, their potential action on or
interaction with B cells remained poorly understood. Here we demonstrate that
human polymorphonuclear MDSCs differentially modulate B-cell function by
suppressing B-cell proliferation and antibody production. We further demonstrate
that this MDSC-mediated effect is cell contact dependent and involves established
mediators such as arginase-1, nitric oxide (NO), reactive oxygen species (ROS) as
well as B-cell death. Collectively, our studies provide novel evidence that human
MDSCs modulate B cells, which could have future implications for immunotherapy
approaches.
PMID- 28687235
TI - Synthesis and evaluation of 26-amino acid methyl ester substituted sarsasapogenin
derivatives as neuroprotective agents for Alzheimer's disease.
AB - Sarsasapogenin, extracted from Anemarrhena asphodeloides Bunge., has been
reported to protect neurons from H2O2-induced damage. In the current study, four
series of 26-amino acid methyl ester substituted sarsasapogenin derivatives (5a
5e, 5f-5j, 6a-6e and 7a-7e) were synthesized and tested for neuroprotective
activity by evaluating their neuroprotective ratio against SH-SHY5Y cell lines.
Studies showed that most of the target compounds displayed better neuroprotective
effects than that of sarsasapogenin. Structure-activity relationship analysis
suggested that 3-methoxy derivatives (5f-5j) were more potent than other series
and the phenylalanine methyl ester moiety at C-26 was important for exhibiting
apparent neuroprotective activity. It was worth noting that compound 5h exhibited
optimal neuroprotective activity (102.2%) compared with sarsasapogenin (27.3%)
and trolox (40.5%), and this encouraged us to investigate the cellular mechanism
of 5h further. Our investigation revealed that 5h could attenuate H2O2-induced
cell damage by inhibiting the expression of cleaved poly (ADP-ribose) polymerase
(PARP) and cleaved caspase-3 as well as rescuing the downregulation of brain
derived neurotrophic factor (BDNF) and its tyrosine receptor kinase B (TrkB).
Taken together, these results suggest that the representative compound 5h is a
profound lead compound for further investigation and the sarsasapogenin skeleton
could be a promising structural template for the development of new anti
Alzheimer drug candidates.
PMID- 28687236
TI - Sevoflurane suppresses microglial M2 polarization.
AB - Microglia can be polarized into the classical (M1) or alternative (M2) activation
states in response to various stimuli. The M2 phenotype has its own set of
receptor profiles, cytokine production, and chemokine secretion, of which
arginase 1 (Arg1), chitinase 3-like 3 (Chi3l3, Ym1), and IL-10 have
neuroprotective properties. Sevoflurane is one of the most commonly used volatile
anesthetics in clinics. Previous studies have shown that sevoflurane promotes
microglial M1 activation. However, it remains unclear whether sevoflurane
regulates microglial M2 activation. In this study, we found that sevoflurane
treatment abolished interleukin 4 (IL-4)-induced M2 microglial activation. Our
results indicate that IL-4-mediated induction of the characteristic M2 marker
genes and proteins Arg1, Ym1, and IL-10 was significantly attenuated by
sevoflurane pretreatment in primary microglia. Microglial M2 polarization induced
by incubation with culture supernatant from human umbilical cord mesenchymal
stromal cells (HUC-MSCs) was abolished by treatment with 2% or 4% sevoflurane.
Upregulation of SOCS1 and suppression of SOCS3 were shown to play a crucial role
in the process of M2 microglial polarization. Our results also indicate that
SOCS1 expression was induced by IL-4, but it was inhibited by pretreatment with
sevoflurane. In contrast, IL-4 suppressed SOCS3 expression, which was restored by
pretreatment with sevoflurane. Mechanistically, it was shown that sevoflurane
suppresses STAT6 phosphorylation in primary microglia.
PMID- 28687237
TI - The pulvinar nucleus is associated with the presence of dysarthria in patients
with basal ganglia hemorrhage.
AB - Dysarthria is a frequent symptom in patients with stroke. The anatomical
structures responsible for dysarthria have been reported in patients with lacunar
infarcts, but the related lesions in patients with basal ganglia hemorrhage (BGH)
have not been investigated. The aim of this study was to identify associations
between the lesion location and the presence/absence of dysarthria in patients
with BGH using voxel-based lesion symptom mapping (VLSM) analyses. A
retrospective analysis was conducted on 26 patients with acute BGH (mean age,
54.0 years; men:women, 14:12) who underwent conservative management. The patients
were classified into groups based on the presence or absence of dysarthria at the
time of admission, which was determined by reviewing the patients' medical
records. Brain lesions were traced on magnetic resonance images that were
acquired within the first 3 weeks after BGH onset, and then separate high
resolution region-of-interest images were generated. Associations between
dysarthria and the lesion location were determined with the VLSM analyses. The
average volume of the delimited lesions was 7.38+/-5.75cm3. The VLSM analyses
identified several voxel clusters, mainly in the pulvinar nucleus of the left
thalamus, that were significantly related to the presence of dysarthria at
admission. These findings suggest that patients with BGH extending into the left
pulvinar nucleus should be monitored for dysarthria.
PMID- 28687238
TI - Assessment of the mutagenic potential of hexavalent chromium in the duodenum of
big blue(r) rats.
AB - A cancer bioassay on hexavalent chromium Cr(VI) in drinking water reported
increased incidences of duodenal tumors in B6C3F1 mice at exposures of 30-180ppm,
and oral cavity tumors in F344 rats at 180ppm. A subsequent transgenic rodent
(TGR) in vivo mutation assay in Big Blue(r) TgF344 rats found that exposure to
180ppm Cr(VI) in drinking water for 28days did not increase cII transgene mutant
frequency (MF) in the oral cavity (Thompson et al., 2015). Herein, we extend our
analysis to the duodenum of these same TgF344 rats. At study termination,
duodenum chromium levels were below either the limit of detection or
quantification in control rats, but were 24.6+/-3.8MUg/g in Cr(VI)-treated rats.
The MF in control (23.2*10-6) and Cr(VI)-treated rats (22.7*10-6) were nearly
identical. In contrast, the MF in the duodenum of rats exposed to 1-ethyl-1
nitrosourea for six days (study days 1, 2, 3, 12, 19, 26) increased 24-fold to
557*10-6. These findings indicate that mutagenicity is unlikely an early
initiating event in Cr(VI)-induced intestinal carcinogenesis.
PMID- 28687239
TI - Novel insights into cardiomyocytes provided by atomic force microscopy.
AB - Cardiovascular diseases (CVDs) are the number one cause of death globally,
therefore interest in studying aetiology, hallmarks, progress and therapies for
these disorders is constantly growing. Over the last decades, the introduction
and development of atomic force microscopy (AFM) technique allowed the study of
biological samples at the micro- and nanoscopic level, hence revealing noteworthy
details and paving the way for investigations on physiological and pathological
conditions at cellular scale. The present work is aimed to collect and review the
literature on cardiomyocytes (CMs) studied by AFM, in order to emphasise the
numerous potentialities of this approach and provide a platform for researchers
in the field of cardiovascular diseases. Original data are also presented to
highlight the application of AFM to characterise the viscoelastic properties of
CMs.
PMID- 28687240
TI - Integrating a post-column makeup pump into preparative supercritical fluid
chromatography systems to address stability and recovery issues during
purifications.
AB - Purification of many pharmaceutical compounds by supercritical fluid
chromatography (SFC) has always been challenging because of degradation of
compound during the isolation step in the presence of acidic or basic modifiers
in the mobile phase. Stability of such acid or base-sensitive compounds could be
improved by post-column addition of a solvent containing base or acid modifier as
counter ion through a make-up pump respectively to neutralize the compound
fraction without affecting the resolution. One such case study has been presented
in this work where the stability of a base-sensitive compound was addressed by
the addition of acidic co-solvent through the make-up pump. Details of this setup
and the investigation of degradation of the in-house base-sensitive compound are
discussed in this paper. In addition, poor retentivity and low recovery of many
non-polar compounds in SFC eluting under low co-solvent percentage is another
major concern. Even though the desired separation could be achieved with low
percentage of co-solvent, it's difficult to get the proper recovery after
purification due to precipitation of the sample and significant aerosol formation
inside the cyclone. We have demonstrated the first-time use of a post-column make
up pump on SFC 350 system to introduce additional solvent prior to cyclone to
avoid the precipitation, reduce the aerosol formation and thus improve the
recovery of non-polar compounds eluting under less than 10% of co-solvent.
PMID- 28687241
TI - Perfluorinated alcohol induced coacervates as extraction media for proteomic
analysis.
AB - We describe a novel method for using hexafluoroisopropanol (HFIP) induced
coacervates with a variety of surfactants to extract proteins from a yeast whole
cell lysate and conduct a global proteomic investigation on the extracted
proteins. Yeast whole cell lysates were prepared and proteins were extracted
using two workflows: 1) Proteins were extracted into the coacervate generated
from the mixture of HFIP, surfactant, and cell lysate. 2) Proteins were extracted
from cell lysate using a surfactant solution, and HFIP was added to the
supernatant to generate a coacervate phase with concentrated proteins. Both
initial extractions were followed by a modified filter-aided sample preparation
(FASP) cleanup. The methodology yields significant protein concentrations in the
coacervate phase (2-3 orders of magnitude increase in concentration) and an
increase in proteome sequence coverage (+5%), membrane proteins identifications
(+50%), and identification of proteins from low abundance cellular subfractions
(>10% of total IDs).
PMID- 28687242
TI - Solvent-saturated solid matrix technique for increasing the efficiency of
headspace extraction of volatiles.
AB - Due to the slow mass transfer rate of substance in solid media, very limited
amount of volatiles can be released from the solid matrix to the headspace in the
static headspace analysis. Thus, low sensitivity is often the main problem of
static headspace analysis of the volatiles contained in a solid sample. Here, we
reported on a solvent-saturated solid matrix (SSSM) technique which successfully
enhanced the headspace extraction efficiency, and improved the sensitivity of the
headspace analysis of the volatiles in solid sample. By adding a small amount of
high-boiling-point solvent (e.g. glycerin) onto the solid sample to form a
surface-covered solvent layer, the headspace extraction efficiency can be
significantly increased by up to 2.5 times higher than that of the conventional
one. Based on the experimental investigation of the performance of different
amounts of solvent used for the headspace extraction of volatiles in air-dried
lotus flower samples, the possible mechanism for the SSSM assisted headspace
extraction has been proposed and validated, which showed that a saturation point
of solvent existed for a given amount of solid sample, and the maximum extraction
efficiency could be obtained at this saturation point. Moreover, positive results
were also achieved when applying this new technique in the headspace extraction
of the volatiles to the other two solid samples, which means this newly developed
technique may open up a new avenue, and also serve as a general strategy for
improving the sensitivity of headspace analysis of the volatiles entrapped in
solid matrices.
PMID- 28687243
TI - Biliary reconstruction options for bile duct stricture in patients with prior
Roux-en-Y reconstruction.
AB - Comprehensive description with illustrations of the 4 biliary reconstruction
options for bile duct injury in patients with history of Roux-en-Y gastric
bypass.
PMID- 28687244
TI - Positive Association of Obesity and Insulin Resistance With Bone Mineral Density
in Tunisian Postmenopausal Women.
AB - The association of bone mineral density (BMD) with obesity and insulin resistance
remains unclear. This study aimed to explore these associations in Tunisian
menopausal women. Eighty-one postmenopausal women were recruited. Data were
analyzed for obese (N = 57) and non-obese women (N = 24) and for insulin
resistant (N = 43) and non insulin-resistant women (N = 36). Anthropometric and
biochemical parameters were recorded. BMD in different sites and body composition
were measured using dual-energy X-ray absorptiometry. Higher BMD was observed in
obese women than those non-obese in the left femur (p = 0.0067), right femur (p =
0.0108), total hip (p = 0.0077), and the whole body (p = 0.0276). Also BMD was
significantly greater in insulin-resistant women than in non-insulin-resistant
women when measured in the left femur and total hip. Positive correlations were
recorded between BMD and anthropometric parameters, body composition parameters,
and glycemia (r = 0.249, p < 0.05). Multiple linear regression analysis shows
that only trunk fat (p < 0.05) and lean mass (p < 0.05) were independently and
positively related to BMD, and the waist circumference was the only
anthropometric parameter independently and negatively associated to BMD. BMD is
improved in obese and insulin-resistant women. Also, trunk fat and lean mass are
likely to be key positive independent factors for BMD.
PMID- 28687245
TI - Movement.
AB - Primary ciliary dyskinesia is an inherited disease characterized by impaired
ciliary function leading to diverse clinical manifestations, including chronic
sinopulmonary disease, persistent middle ear effusions, laterality defects, and
infertility. Our understanding of the complex genetics and functional phenotypes
of primary ciliary dyskinesia has rapidly grown, and over 35 disease-associated
genes have been identified, which segregate into genes that encode axonemal motor
proteins, regulatory proteins within the cilium, and cytoplasmic proteins
involved in ciliary assembly. These findings have yielded unexpected insights
into the clinical heterogeneity of disease and are beginning to revolutionize
diagnostic testing for primary ciliary dyskinesia.
PMID- 28687246
TI - Edwin Lawrence Kendig, Jr. MD DSc (hon) 1911-2003.
AB - Edwin Kendig, MD is considered one of the founders of pediatric pulmonology.
Prompted by his own experience with tuberculosis, he opened a 'chest clinic' for
children, where he worked for 50years. He systematically published his
observations and was the original editor of the first textbook in pediatric
pulmonology in 1967. His book, now called Kendig and Chernick's Disorders of the
Respiratory Tract in Children will publish its 9th edition in 2018. All of this
was in addition to his primary care pediatric practice, his teaching and his work
at the national and international level of pediatric care. In his lifetime, he
received many awards, including the establishment of the annual Edwin L. Kendig,
Jr. Award from the American Academy of Pediatrics given for lifetime achievement
in pediatric pulmonology.
PMID- 28687247
TI - Bacterial and viral pneumonia: New insights from the Drakenstein Child Health
Study.
AB - Pneumonia remains the major cause of childhood morbidity and mortality globally,
despite improved preventative strategies. Increasing evidence also links early
life pneumonia with the development of chronic non-communicable respiratory
diseases into childhood and adulthood. The Drakenstein Child Health Study is a
unique, multidisciplinary, South African birth cohort, investigating the
incidence, risk factors, aetiology and long term impact of early life pneumonia
on child health. The study provides novel data showing a high incidence of
pneumonia despite excellent immunisation coverage; that pneumonia is due to
multiple pathogens; that dysbiosis of the nasopharyngeal flora precedes and
predisposes to pneumonia; and that early life pneumonia results in reduced lung
function.
PMID- 28687248
TI - Device Therapy for Rate Control: Pacing, Resynchronisation and AV Node Ablation.
AB - Atrioventricular node ablation (AVNA) is generally reserved for patients whose
atrial fibrillation (AF) is refractory all other therapeutic options, since the
recipients will often become pacemaker dependent. In such patients, this approach
may prove particularly useful, especially if a tachycardia-induced cardiomyopathy
is suspected. Historically, an "ablate and pace" approach has involved AVNA and
right ventricular pacing, with or without an atrial lead. There is also an
evolving role for atrioventricular node ablation in patients with AF who require
cardiac resynchronisation therapy for treatment of systolic heart failure. A
mortality benefit over pharmacotherapy has been demonstrated in observational
studies and this concept is being further investigated in multi-centre randomised
control trials.
PMID- 28687249
TI - Etiopathogenesis of oncocytomas.
AB - Oncocytomas are distinct tumors characterized by an abnormal accumulation of
defective and (most probably) dysfunctional mitochondria in cell cytoplasm of
such tumors. This particular phenotype has been studied for the last decades and
the clarification of the etiopathogenic causes are still needed. Several
mechanisms involved in the formation and maintenance of oncocytomas are accepted
as reasonable causes, but the relevance and contribution of each one for
oncocytic transformation may depend on different cancer etiopathogenic contexts.
In this review, we describe the current knowledge of the etiopathogenic events
that may lead to oncocytic transformation and discuss their contribution for
tumor progression and mitochondrial accumulation.
PMID- 28687250
TI - Trends in the incidence of primary malignant brain tumors in Taiwan and
correlation with comorbidities: A population-based study.
AB - OBJECTIVE: Primary malignant brain tumors are relatively uncommon, and their
incidence and survival rates have seldom been reported. PATIENTS AND METHODS: We
identified all patients with malignant brain tumors in Taiwan between 1997 and
2012 using the National Health Insurance database. We estimated the stratified
incidence of malignant brain tumors by age and sex. We estimated the median 1-, 2
, and 5-year survival, taking comorbidities into account. Trends for incidence
and survival were analyzed using Joinpoint regression. The incidence in different
geographic areas was also evaluated. RESULTS: A total of 7746 men and 5846 women
were identified. The incidence of malignant brain tumor was 3.34 (95% CI, 3.09
3.59) per 100,000 person-years in 1997 and 3.82 (95% CI, 3.56-4.08) per 100,000
person-years in 2012. The average annual percentage change (APC) of the
standardized incidence over this period was 0.1 (95% CI, -1.9 to 2.2), suggesting
a relatively stable incidence. However, the incidence significantly decreased
between 1999 and 2012, with an APC of -1.8 [95% CI, -2.5 to -1.0]. One- and 5
year survival was 53.8% (50.0%-57.5%) and 27.5% (24.1%-30.9%) in 1997 and 67.6%
(64.3%-70.7%) and 32.8% (29.6%-35.9%) in 2012. The average APC was 1.1 (95% CI,
0.7-1.5) for 1-year survival and 0.2 (95% CI, -1.0-1.4) for 5-year survival. The
trend of improvement in the survival rate was seen for short-term but not long
term survival, especially in the group with more comorbidities. CONCLUSIONS: A
slightly decreased trend in incidence of primary malignant brain tumors was
observed in Taiwanese general population since 1999. Over the past 15 years, the
short-term survival of malignant brain tumors has improved, especially in adults.
PMID- 28687251
TI - Associations between acute GVHD-related biomarkers and endothelial cell
activation after allogeneic hematopoietic stem cell transplantation.
AB - BACKGROUND: Hematopoietic stem cell transplantation (HSCT) can cause serious
transplant-related complications such as graft-versus-host disease (GVHD). Acute
GVHD (aGVHD) has been diagnosed by clinical manifestations, laboratory data and
pathological effects until now, but recently the discovery of specific biomarkers
such as suppression of tumorigenicity 2 (ST2), elafin and regenerating islet
derived 3alpha (REG3alpha) is challenging this approach. METHODS: We investigated
the expression of aGVHD-related markers (regulated on activation normal T-cell
expressed and secretes: RANTES, elafin, REG3alpha and ST2) and endothelial cell
activation markers (soluble vascular cell adhesion molecule: sVCAM-1 and
plasminogen activator inhibitor: PAI-1) in patients undergoing allogeneic HSCT.
Additionally, we studied the effects of recombinant soluble thrombomodulin (rTM)
on the expression of these markers. Our study cohort included 225 patients who
underwent allogeneic HSCT at several institutions in Japan. RESULTS: RANTES,
sVCAM-1, PAI-1, elafin, REG3alpha and ST2 exhibited significant increases in
patients not receiving rTM after HSCT. When we examined patients with confirmed
complications, the frequencies of aGVHD and VOD were significantly lower in the
rTM-treated group. In addition, aGVHD-related biomarkers such as elafin,
REG3alpha, and ST2 were elevated significantly in patients with aGVHD.
CONCLUSION: Our findings suggest that endothelial cell activation might be linked
to aGVHD, and that rTM might act to prevent aGVHD, at least in part, through its
effect on endothelial cells.
PMID- 28687252
TI - Treatment of early-onset scoliosis with a hybrid of a concave magnetic driver
(magnetic controlled growth rod) and a contralateral passive sliding rod
construct with apical control: preliminary report on 17 cases.
AB - BACKGROUND CONTEXT: Magnetic controlled growth rods (MCGRs) are increasingly
popular for surgical treatment of severe early-onset scoliosis (EOS), because
they allow noninvasive extensions with good growth maintenance. We combined an
MCGR with a contralateral passive sliding rod construct with apical control on
the convex side to improve efficiency in terms of costs and three-dimensional
(3D) correction. PURPOSE: To investigate the feasibility, 3D correction, spinal
growth, and complications of the apical control MCGR sliding rod hybrid. STUDY
DESIGN: Two-center retrospective cohort study. PATIENT SAMPLE: A consecutive
series of 17 children with EOS from two European spine centers were treated with
the hybrid principle: 13 primary cases and 4 conversion cases from other growth
instrumentation. Median age at surgery was 9 years (range: 6-18). Median follow
up time was 24 months (range: 12-31). OUTCOMES: Cobb angles (frontal Cobb,
kyphosis, lordosis), rotation, spinal length gain, growth rate, and
complications. METHODS: Radiographs and patient files were reviewed. All the
patients received fully financed treatment within the national public health-care
systems. RESULTS: Mean preoperative frontal Cobb angle was 59 degrees , reduced
postoperatively to 30 degrees and was maintained throughout follow-up. Mean
rotation of the apical vertebra improved from 27 degrees to 18 degrees , but was
partially lost over time. Kyphosis decreased and lordosis was largely unaltered.
Instrumented spine growth was maintained at a mean of 12 mm per year. One child
had surgical revision because of progressive trunk shift, unrelated to the
technique. The same child fell and sustained T1 and T2 fractures that were
treated conservatively. Another child is planned for revision because of MCGR
distraction failure. CONCLUSION: These early results show satisfactory frontal
Cobb curve reduction and maintenance of spinal growth after using a new hybrid
concept of a single magnetic growth rod and contralateral apical control sliding
rods. A single magnetic growth rod in this combination may work equally well as
traditional or dual magnetic growth rods. This new concept may represent a
significant gain in both cost-effectiveness of growth rod treatment and 3D
correction in EOS.
PMID- 28687254
TI - [Tacit and explicit knowledge: comparative analysis of the prioritization of
maternal health problems in Mexico].
AB - OBJECTIVE: To identify coincidences and differences in the identification and
prioritization of maternal healthcare service problems in Mexico based on the
perspective of tacit knowledge and explicit knowledge that may offer evidence
that can contribute to attaining the Sustainable Development Goals. METHODS:
Mixed study performed in three stages: 1) systematization of maternal healthcare
service problems identified by tacit knowledge (derived from professional
experience); 2) identification of maternal healthcare service problems in Latin
America addressed by explicit knowledge (scientific publications); 3) comparison
between the problems identified by tacit and explicit knowledge. RESULTS: The
main problems of maternal health services identified by tacit knowledge are
related to poor quality of care, while the predominant problems studied in the
scientific literature are related to access barriers to health services.
Approximately, 70% of the problems identified by tacit knowledge are also
mentioned in the explicit knowledge. Conversely, 70% of the problems identified
in the literature are also considered by tacit knowledge. Nevertheless, when
looking at the problems taken one by one, no statistically significant
similarities were found. CONCLUSIONS: The study discovered that the
identification of maternal health service problems by tacit knowledge and
explicit knowledge is fairly comparable, according to the comparability index
used in the study, and highlights the interest of integrating both approaches in
order to improve prioritization and decision making towards the Sustainable
Development Goals.
PMID- 28687255
TI - Gastric neumatosis: When not to operate.
PMID- 28687253
TI - Connexin hemichannel inhibition reduces acetaminophen-induced liver injury in
mice.
AB - Historically, connexin hemichannels have been considered as structural precursors
of gap junctions. However, accumulating evidence points to independent roles for
connexin hemichannels in cellular signaling by connecting the intracellular
compartment with the extracellular environment. Unlike gap junctions, connexin
hemichannels seem to be mainly activated in pathological processes. The present
study was set up to test the potential involvement of hemichannels composed of
connexin32 and connexin43 in acute hepatotoxicity induced by acetaminophen. Prior
to this, in vitro testing was performed to confirm the specificity and efficacy
of TAT-Gap24 and TAT-Gap19 in blocking connexin32 and connexin43 hemichannels,
respectively. Subsequently, mice were overdosed with acetaminophen followed by
treatment with TAT-Gap24 or TAT-Gap19 or a combination of both after 1.5h.
Sampling was performed 3, 6, 24 and 48h following acetaminophen administration.
Evaluation of the effects of connexin hemichannel inhibition was based on a
series of clinically relevant read-outs, measurement of inflammatory cytokines
and oxidative stress. Subsequent treatment of acetaminophen-overdosed mice with
TAT-Gap19 only marginally affected liver injury. In contrast, a significant
reduction in serum alanine aminotransferase activity was found upon
administration of TAT-Gap24 to intoxicated animals. Furthermore, co-treatment of
acetaminophen-overdosed mice with both peptides revealed an additive effect as
even lower serum alanine aminotransferase activity was observed. Blocking of
connexin32 or connexin43 hemichannels individually was found to decrease serum
quantities of pro-inflammatory cytokines, while no effects were observed on the
occurrence of hepatic oxidative stress. This study shows for the first time a
role for connexin hemichannels in acetaminophen-induced acute liver failure.
PMID- 28687256
TI - Improved survival with palliative surgery and chemotherapy for Mixed
adenoneuroendocrine carcinoma of the gastroesophageal junction with liver
metastases.
PMID- 28687257
TI - Delaying implant-based mammary reconstruction after radiotherapy does not
decrease capsular contracture: An in vitro study.
AB - The most common complications of irradiated implant-based mammary reconstruction
are fibrosis and capsular contracture. The indications for postmastectomy
adjuvant radiotherapy have considerably broadened. Facing an increased number of
patients who will require radiotherapy, most guidelines recommend delaying
reconstruction after radiotherapy to prevent long-term fibrotic complications.
Does radiotherapy permanently alter cellular properties which will adversely
affect implant-based reconstruction? If so, is there a benefit in delaying
reconstruction after radiotherapy? Our in vitro model simulates two implant-based
mammary reconstruction approaches: the irradiated implant and the delayed implant
reconstructions by using an implant inset beneath healthy non-irradiated tissue
post radiotherapy. We performed cell culture of fibroblasts and endothelial cells
to simulate these two surgical conditions. Irradiated fibroblasts simulate the
capsular tissue seen around the breast implant. The delayed reconstruction
approach is simulated by non-irradiated fibroblasts conditioned with supernatant
culture media obtained from irradiated endothelial cells. Irradiation induced
fibrosis through fibroblast differentiation into myofibroblasts, as demonstrated
by increased alpha-smooth-muscle actin levels in fibroblasts. This constitutes
the basis for scar tissue contraction observed in irradiated implant-based breast
reconstruction. Irradiation of endothelial cells induced irreversible cell cycle
arrest known as senescence and secretion of the profibrotic connective tissue
growth factor. Non-irradiated fibroblasts conditioned with culture media obtained
from irradiated endothelial cells exhibited myofibroblast differentiation and the
expression of fibrotic phenotype akin to capsular contracture. Our results
demonstrate that radiotherapy causes irreversible cellular changes, which
permanently alter the microenvironment in favor of fibrosis. Given that these
changes are permanent, delaying reconstruction does not present an advantage in
preventing capsular contracture.
PMID- 28687258
TI - Sensory recovery of the breast after innervated and non-innervated autologous
breast reconstructions: A systematic review.
AB - BACKGROUND: The sensory recovery of the reconstructed breast is an undervalued
topic in the field of autologous breast reconstruction. This systematic review
aimed to evaluate the available literature on the sensory recovery of the breast
after innervated and non-innervated autologous breast reconstructions and to
assess the possible benefits of sensory nerve coaptation compared to spontaneous
reinnervation of the flap. METHODS: A comprehensive literature search was
conducted in PubMed, Embase and the Cochrane Library to identify all eligible
studies regarding the sensory recovery of all types of innervated and non
innervated autologous breast reconstructions. RESULTS: The search yielded 334
hits, of which 32 studies concerning 1177 breast reconstructions were included.
The amount of heterogeneity between the studies was high, which made the pooling
of data difficult. The studies indicated that spontaneous reinnervation of
autologous breast reconstructions occurred to a variable extent, depending on how
and when it was measured. Despite these variable results, the sensory recovery of
innervated flaps, however, was superior, started earlier and gradually improved
over time with a higher chance of approaching normal values than non-innervated
flaps. There is a lack of studies that assess the return of erogenous sensation
and quality of life. CONCLUSION: The current evidence shows that nerve coaptation
results in superior sensory recovery of the reconstructed breast compared to
spontaneous reinnervation of the flap. This review illustrates that more
standardised, high-quality studies with adequate sample sizes are needed to
objectively evaluate the sensory recovery of the breast after autologous breast
reconstructions.
PMID- 28687259
TI - Why does Finland have the highest dementia mortality rate? Environmental factors
may be generalizable.
AB - Finland has the highest death rate from dementia in the world and its
environmental features can be instructive in understanding hidden causes of
dementia. Environmental factors there include: 1) a climate that is both very
cold and humid resulting in housing frequently harboring molds that are capable
of producing a neurotoxic mycotoxin 2) the Gulf of Finland as well as Finnish
lakes harbor cyanobacteria that produce the neurotoxin, beta-N-methyl amino-L
alanine, known to cause dementia and related disorders 3) the aforementioned
toxins can be potentiated by the presence of mercury and methyl mercury which can
be found in Finnish waters 4) soil in Finland is naturally low in selenium and
selenium deficiency may reduce the quantity and effectiveness of glutathione's
ability to protect against neurotoxins. A high rate of fatal dementia could be
the consequence of these environmental factors. Studies that can support or
disprove this hypothesis are suggested. Such environmental toxins are likely to
promote Alzheimer's disease elsewhere in the world where such a combination of
neurotoxins may also occur.
PMID- 28687260
TI - A survey of Australian midwives' knowledge, experience, and training needs in
relation to female genital mutilation.
AB - BACKGROUND: Female genital mutilation (FGM) involves partial or total removal of
the external female genitalia or any other injury for non-medical reasons. Due to
international migration patterns, health professionals in high income countries
are increasingly caring for women with FGM. Few studies explored the knowledge
and skills of midwives in high income countries. AIM: To explore the knowledge,
experience and needs of midwives in relation to the care of women with FGM.
METHODS: An online self-administered descriptive survey was designed and
advertised through the Australian College of Midwives' website. RESULTS: Of the
198 midwives (24%) did not know the correct classification of FGM. Almost half of
the respondents (48%) reported they had not received FGM training during their
midwifery education. Midwives (8%) had been asked, or knew of others who had been
asked to perform FGM in Australia. Many midwives were not clear about the law or
health data related to FGM and were not aware of referral paths for affected
women. CONCLUSION: As frontline providers, midwives must have appropriate up-to
date clinical skills and knowledge to ensure they are able to provide women with
FGM the care they need and deserve. Midwives have a critical role to play in the
collection of FGM related data to assist with health service planning and to
prevent FGM by working closely with women and communities they serve to educate
and advocate for its abandonment. Therefore, addressing educational gaps and
training needs are key strategies to deliver optimal quality of care.
PMID- 28687261
TI - Bone Density Testing Is the Best Way to Monitor Osteoporosis Treatment.
PMID- 28687262
TI - Renal Function and Direct Oral Anticoagulant Treatment for Venous
Thromboembolism.
AB - Because differences in renal function can affect the efficacy and safety of
direct oral anticoagulants, prescribing an appropriate dose based on renal
function is critical, especially in patient populations with a high incidence of
renal impairment. In patients with nonvalvular atrial fibrillation and mild or
moderate renal impairment, direct oral anticoagulants are associated with a
better risk-benefit profile compared with warfarin. However, less is known
regarding outcomes in patients with venous thromboembolism and renal impairment.
The efficacy and safety of direct oral anticoagulants in patients with venous
thromboembolism and renal impairment are primarily derived from prespecified
subgroup analyses of the phase 3 clinical trials. We summarize the available data
on direct oral anticoagulant use in patients with venous thromboembolism and
renal impairment. Clinicians are encouraged to follow study inclusion/exclusion
criteria and perform renal dose adjustments based on the Cockcroft-Gault equation
using actual body weight when indicated to avoid adverse events.
PMID- 28687263
TI - Brief Mindfulness Practices for Healthcare Providers - A Systematic Literature
Review.
AB - Mindfulness practice, where an individual maintains openness, patience, and
acceptance while focusing attention on a situation in a nonjudgmental way, can
improve symptoms of anxiety, burnout, and depression. The practice is relevant
for health care providers; however, the time commitment is a barrier to practice.
For this reason, brief mindfulness interventions (eg, <= 4 hours) are being
introduced. We systematically reviewed the literature from inception to January
2017 about the effects of brief mindfulness interventions on provider well-being
and behavior. Studies that tested a brief mindfulness intervention with hospital
providers and measured change in well-being (eg, stress) or behavior (eg, tasks
of attention or reduction of clinical or diagnostic errors) were selected for
narrative synthesis. Fourteen studies met inclusion criteria; 7 were randomized
controlled trials. Nine of 14 studies reported positive changes in levels of
stress, anxiety, mindfulness, resiliency, and burnout symptoms. No studies found
an effect on provider behavior. Brief mindfulness interventions may be effective
in improving provider well-being; however, larger studies are needed to assess an
impact on clinical care.
PMID- 28687264
TI - Calculated Bicarbonate for Acid-Base Disorders.
PMID- 28687265
TI - Contextualizing Myocardial Infarction: Comorbidities and Priorities in Older
Adults.
AB - Cardiovascular care for older adults has become increasingly complex owing to a
rise in the concurrent comorbidity burden that accompanies senescence.
Internists, hospitalists, and cardiologists often encounter geriatric patients
with multiple chronic conditions needing acute cardiovascular care. Abnormal
cardiac biomarker levels in patients with multiple noncardiac conditions are a
common reason for older adults to enter the hospital. This type of acute coronary
syndrome, defined as a non-ST segment elevation myocardial infarction or, more
precisely, type 2 myocardial infarction, often leads to substantial
consternation. Although guideline-based single-disease care may be appropriate in
younger individuals, a more cautious approach is needed when considering optimal
care strategies for older adults. We discuss a case of an older adult presenting
with type 2 myocardial infarction, to highlight a modern-day approach that
requires a deliberate shift from an evidence-based focus to a more value-based
geriatric mindset.
PMID- 28687266
TI - Not Your Typical Renal Cyst.
PMID- 28687267
TI - Cultivating Communication with Patients.
PMID- 28687268
TI - An Overlooked Cause of Hypokalemia.
PMID- 28687269
TI - Chemopreventive effects of a Tamarindus indica fruit extract against colon
carcinogenesis depends on the dietary cholesterol levels in hamsters.
AB - Tamarind has significant antioxidant potential. We showed that tamarind protects
hypercholesterolemic hamsters from atherosclerosis. Hypercholesterolemia might
increase the risk of colon cancer. We investigated whether tamarind extract
modulates the risk of colon cancer in hypercholesterolemic hamsters. Hamsters (n
= 64) were given tamarind and a hypercholesterolemic diet for 8 weeks. The groups
were the control, tamarind treatment, hypercholesterolemic, and
hypercholesterolemic treated with tamarind groups. Half of each group was exposed
to the carcinogen dimethylhydrazine (DMH) at the 8th week. All hamsters were
euthanatized at the 10th week. In carcinogen-exposed hypercholesterolemic
hamsters, tamarind did not alter the cholesterol or triglyceride serum levels,
but it reduced biomarkers of liver damage (alanine transaminase [ALT], and
aspartate aminotransferase [AST]). Tamarind decreased DNA damage in hepatocytes,
as demonstrated by analysis with an anti-gammaH2A.X antibody. In liver and serum
samples, we found that this fruit extract reduced lipid peroxidation
(thiobarbituric acid reactive substances [TBARS]) and increased endogenous
antioxidant mechanisms (glutathione peroxidase [GPx] and superoxide dismutase
[SOD]). However, tamarind did not alter either lipid peroxidation or antioxidant
defenses in the colon, which contrasts with DMH exposure. Moreover, tamarind
significantly increased the stool content of cholesterol. Although tamarind
reduced the risk of colon cancer in hypercholesterolemic hamsters that were
carcinogenically exposed to DMH by 63.8% (Metallothionein), it was still ~51%
higher than for animals fed a regular diet. Staining colon samples with an anti
gammaH2A.X antibody confirmed these findings. We suggest that tamarind has
chemoprotective activity against the development of colon carcinogenesis,
although a hypercholesterolemic diet might impair this protection.
PMID- 28687271
TI - Number of thoracotomies predicts impairment in lung function and exercise
capacity in patients with congenital heart disease.
AB - OBJECTIVE: Many patients with congenital heart disease (CHD) require surgery to
ensure survival into adulthood. But history of previous thoracotomies is
associated with respiratory muscle weakness, impairments in chest wall
compliance, and moderately to severely impaired lung function. This study
evaluated the impact of thoracotomies on functional outcome in patients with CHD.
PATIENTS AND METHODS: In total 1372 adolescents and adults with CHD (32.4+/-11.5
years, 624 female), who underwent spirometry and cardiopulmonary exercise testing
in our institution from January 2010 to August 2015, were analyzed. RESULTS:
After adjusting for confounding variables, with every thoracotomy the prevalence
for a restrictive ventilatory pattern increased by 1.8-fold (CI: 1.606-2.050;
p<0.001). The number of thoracotomies had no direct influence on an impaired
exercise capacity in a multivariate model, but with every percentage point
increase in forced vital capacity probability of impaired exercise capacity
diminished (OR: 0.944, CI: 0.933-0.955, p<0.001). There was a moderate
correlation of forced vital capacity and peak oxygen uptake (r=0.464, p<0.001).
After a follow-up of 2.1+/-1.6 years 21 patients had died. Survival was only
related to age (p<0.001) and peak oxygen uptake (p<0.001) after considering
together with thoracotomies, oxygen saturation at rest and forced vital capacity
in a multivariate model. CONCLUSIONS: Independent of CHD complexity and other
risk factors, multiple thoracotomies lead to restrictive lung pattern. It could
be suggested that those limitations in forced vital capacity contribute to
impairments in exercise capacity, which turned out to be the strongest predictor
for survival.
PMID- 28687270
TI - RIFM fragrance ingredient safety assessment, p-methoxybenzonitrile, CAS Registry
Number 874-90-8.
PMID- 28687272
TI - Interstrand Crosslink Repair as a Target for HDAC Inhibition.
AB - DNA interstrand crosslinks (ICLs) covalently connect complementary DNA strands.
Consequently, DNA replication and transcription are hampered, DNA damage
responses (DDR) are initiated, and cell death is triggered. Therefore, drugs
inducing ICLs are effective against rapidly growing cancer cells. However, tumors
engage a complicated enzymatic machinery to repair and survive ICLs. Several
factors, including the post-translational acetylation/deacetylation of lysine
residues within proteins, control this network. Histone deacetylases (HDACs)
modulate the expression and functions of DNA repair proteins which remove ICLs
and control the accessibility of chromatin. Accordingly, histone deacetylase
inhibitors (HDACi) are small, pharmacologically and clinically relevant molecules
that sensitize cancer cells to ICL inducers. We discuss the mechanism of ICL
repair and targets of HDACi within this pathway.
PMID- 28687274
TI - Rapid effects of estrogens and androgens on temporal and spectral features in
ultrasonic vocalizations.
PMID- 28687273
TI - Pharmaceutical aspects of salt and cocrystal forms of APIs and characterization
challenges.
AB - In recent years many efforts have been devoted to the screening and the study of
new solid-state forms of old active pharmaceutical ingredients (APIs) with
salification or co-crystallization processes, thus modulating final properties
without changing the pharmacological nature. Salts, hydrates/solvates, and
cocrystals are the common solid-state forms employed. They offer the intriguing
possibility of exploring different pharmaceutical properties for a single API in
the quest of enhancing the final drug product. New synthetic strategies and
advanced characterization techniques have been recently proposed in this hot
topic for pharmaceutical companies. This paper reviews the recent progresses in
the field particularly focusing on the characterization challenges encountered
when the nature of the solid-state form must be determined. The aim of this
article is to offer the state-of-the-art on this subject in order to develop new
insights and to promote cooperative efforts in the fascinating field of API salt
and cocrystal forms.
PMID- 28687275
TI - Avoidance of Cow's Milk-Based Formula for At-Risk Infants Does Not Reduce
Development of Celiac Disease: A Randomized Controlled Trial.
AB - BACKGROUND & AIMS: Feeding during the first months of life might affect risk for
celiac disease. Individuals with celiac disease or type 1 diabetes have been
reported to have high titers of antibodies against cow's milk proteins. Avoidance
of cow's milk-based formula for infants with genetic susceptibility for type 1
diabetes reduced the cumulative incidence of diabetes-associated autoantibodies.
We performed a randomized controlled trial in the same population to study
whether weaning to an extensively hydrolyzed formula reduced the risk of celiac
disease autoimmunity or celiac disease. METHODS: We performed a double-blind
controlled trial of 230 infants with HLA-defined predisposition to type 1
diabetes and at least 1 family member with type 1 diabetes. The infants were
randomly assigned to groups fed a casein hydrolysate formula (n = 113) or a
conventional formula (control, n = 117) whenever breast milk was not available
during the first 6-8 months of life. Serum samples were collected over a median
time period of 10 years and analyzed for antibodies to tissue transglutaminase
(anti-TG2A) using a radiobinding assay, to endomysium using an immunofluorescence
assay, and antibodies to a deamidated gliadine peptide using an immunofluorometry
assay. Duodenal biopsies were collected if levels of anti-TG2A exceeded 20
relative units. Cow's milk antibodies were measured during the first 2 years of
life. RESULTS: Of the 189 participants analyzed for anti-TG2A, 25 (13.2%) tested
positive. Of the 230 study participants observed, 10 (4.3%) were diagnosed with
celiac disease. We did not find any significant differences at the cumulative
incidence of anti-TG2A positivity (hazard ratio, 1.14; 95% confidence interval,
0.51-2.54) or celiac disease (hazard ratio, 4.13; 95% confidence interval, 0.81
21.02) between the casein hydrolysate and cow's milk groups. Children who
developed celiac disease had increased titers of cow's milk antibodies before the
appearance of anti-TG2A or celiac disease. CONCLUSIONS: In a randomized
controlled trial of 230 infants with genetic risk factors for celiac disease, we
did not find evidence that weaning to a diet of extensively hydrolyzed formula
compared with cow's milk-based formula would decrease the risk for celiac disease
later in life. Increased titers of cow's milk antibody before anti-TG2A and
celiac disease indicates that subjects with celiac disease might have increased
intestinal permeability in early life. ClinicalTrials.gov Number: NCT00570102.
PMID- 28687276
TI - NAP1L1 regulates NF-kappaB signaling pathway acting on anti-apoptotic Mcl-1 gene
expression.
AB - Nuclear factor-kappaB (NF-kappaB) participates in apoptosis signaling pathway
under various pathophysiological conditions. It exerts transcriptional control on
the anti-apoptotic Bcl-2 family, such as Bcl-2, Bcl-xl, and Mcl-1, which act on
the mitochondrial outer membrane. Previously, we described that NF-kappaB is
negatively regulated by diacylglycerol kinase zeta (DGKzeta), an enzyme that
phosphorylates a lipid second messenger diacylglycerol. DGKzeta downregulation
enhances inhibitors of NF-kappaB alpha (IkappaBalpha) degradation and p65 subunit
phosphorylation, leading to enhanced NF-kappaB transcriptional activity.
Transcriptional machinery is tightly regulated by assembly/disassembly and
modification of nucleosomal components. Of those, the human NAP1-like protein
(NAP1L) family functions in the transport, assembly/disassembly of nucleosome
core particles. We previously identified NAP1L1 and NAP1L4 as novel DGKzeta
binding partners, but the mechanism by which NAP1Ls are involved in NF-kappaB
signaling pathway remains unclear. Here we show that knockdown of NAP1L1
suppresses IkappaBalpha degradation and nuclear transport of p65 subunit after
treatment with TNF-alpha stimulation, leading to attenuation of the NF-kappaB
transcriptional activity, whereas NAP1L4 knockdown remains silent. Moreover, ChIP
assay reveals that NAP1L1 knockdown attenuates p65 binding to the Mcl-1 promoter
after TNF-alpha stimulation. This attenuation leads to reduced expression of anti
apoptotic Mcl-1, thereby decreasing the mitochondrial membrane potential and
subsequent apoptosis after treatment with TNF-alpha and CHX. Collectively,
results of this study suggest that NAP1L1 downregulation renders the cell
vulnerable to apoptotic cell death through attenuation of NF-kappaB
transcriptional activity on the anti-apoptotic Mcl-1 gene.
PMID- 28687277
TI - Measurement of tributyl phosphate (TBP) in groundwater at a legacy radioactive
waste site and its possible role in contaminant mobilisation.
AB - At many legacy radioactive waste sites, organic compounds have been co-disposed,
which may be a factor in mobilisation of radionuclides at these sites. Tri-butyl
phosphate (TBP) is a component of waste streams from the nuclear fuel cycle,
where it has been used in separating actinides during processing of nuclear
fuels. Analyses of ground waters from the Little Forest Legacy Site (LFLS) in
eastern Australia were undertaken using solid-phase extraction (SPE) followed by
gas chromatographic mass spectrometry (GCMS). The results indicate the presence
of TBP several decades after waste disposal, with TBP only being detected in the
immediate vicinity of the main disposal area. TBP is generally considered to
degrade in the environment relatively rapidly. Therefore, it is likely that its
presence is due to relatively recent releases of TBP, possibly stemming from
leakage due to container degradation. The ongoing presence and solubility of TBP
has the potential to provide a mechanism for nuclide mobilisation, with
implications for long term management of LFLS and similar legacy waste sites.
PMID- 28687278
TI - Healthcare teams as complex adaptive systems: Focus on interpersonal interaction.
AB - OBJECTIVE: The aim of this study is to test the feasibility of a tool to
objectify the functioning of healthcare teams operating in the complexity zone,
and to evaluate its usefulness in identifying areas for team quality improvement.
METHODS: We distributed The Complex Adaptive Leadership (CALTM) Organisational
Capability Questionnaire (OCQ) to all members of one palliative care team (n=15)
and to palliative care physicians in Flanders, Belgium (n=15). Group discussions
were held on feasibility aspects and on the low scoring topics. Data was analysed
calculating descriptive statistics (sum score, mean and standard deviation). The
one sample T-Test was used to detect differences within each group. RESULTS: Both
groups of participants reached mean scores ranging from good to excellent. The
one sample T test showed statistically significant differences between
participants' sum scores within each group (p<0,001). Group discussion led to
suggestions for quality improvement e.g. enhanced feedback strategies between
team members. CONCLUSION: The questionnaire used in our study shows to be a
feasible and useful instrument for the evaluation of the palliative care teams'
day-to-day operations and to identify areas for quality improvement. PRACTICAL
IMPLICATIONS: The CALTMOCQ is a promising instrument to evaluate any healthcare
team functioning. A group discussion on the questionnaire scores can serve as a
starting point to identify targets for quality improvement initiatives.
PMID- 28687279
TI - The impact of expert- and peer feedback on communication skills of undergraduate
dental students - a single-blinded, randomized, controlled clinical trial.
AB - OBJECTIVE: To evaluate the effect of peer- and expert feedback on communication
skills of undergraduate dental students. METHODS: All students of the first
clinical treatment course (n=46) were randomly assigned into two groups. For
three times a medical-dental interview/consultation of each student with a real
patient was videotaped. After every consultation the videos were assessed either
by a person experienced in communication (expert group) or by a fellow student
(peer group), giving the students feedback regarding their chairside performed
communication skills. Before and after the feedback-interventions all students
conducted an interview with simulated patients, which was rated using a validated
global rating and analyzed statistically. RESULTS: Global ratings mean scores
after feedback-intervention were significantly improved (p<0.05). Thereby, no
significant differences in the overall assessment could be observed between
expert and peer feedback (p>0.05). CONCLUSION: During this study students
improved their communication skills in dentist-patient interactions. The
communication experience of the feedback provider seems not to have any impact on
the communication skills in undergraduate dental students. PRACTICE IMPLICATIONS:
The clinical courses in dentistry offer the opportunity to implement peer
feedback interventions in real treatment situation as part of communication
training to longitudinally improve communication skills.
PMID- 28687280
TI - Prevalence and characteristics of Clostridium perfringens and Clostridium
difficile in dogs and cats attended in diverse veterinary clinics from the Madrid
region.
AB - Despite extensive research on the epidemiology of pathogenic clostridia in dogs
and cats, most published studies focus on a selected animal population and/or a
single veterinary medical centre. We assessed the burden of Clostridium
perfringens and C. difficile shedding by small animals in 17 veterinary clinics
located within the Madrid region (Spain) and differing in size, number and
features of animals attended and other relevant characteristics. In addition, we
studied the genetic diversity and antibiotic susceptibility of recovered
isolates. Selective culture of all fecal specimens collected during a single week
from dogs (n = 105) and cats (n = 37) attended in participating clinics yielded
C. perfringens/C. difficile from 31%, 4.8% of the dogs, and 20%, 0% of the cats
analyzed, respectively, and three dogs yielded both species. Furthermore, 17
animals (15 dogs and two cats) that yielded a positive culture for either species
were recruited for a follow-up survey and C. perfringens was again obtained from
nine dogs. Considerable differences in prevalence were observed among
participating clinics for both clostridial species. C. perfringens isolates (n =
109) belonged to toxinotypes A (97.2%) and E (three isolates from one dog),
whereas C. difficile isolates (n = 18) belonged to the toxigenic ribotypes 106
(33.3%) and 154 (16.7%), a 009-like ribotype (33.3%) and an unknown non-toxigenic
ribotype (16.7%). Amplified fragment length polymorphism-based fingerprinting
classified C. perfringens and C. difficile isolates into 105 and 15 genotypes,
respectively, and tested isolates displayed in vitro resistance to
benzylpenicillin (2.8%, 88.8%), clindamycin (0%, 16.7%), erythromycin (0.9%,
16.7%), imipenem (1.8%, 100%), levofloxacin (0.9%, 100%), linezolid (5.5%, 0%),
metronidazole (4.6%, 0%) and/or tetracycline (7.3%, 0%). All animals from which
multiple isolates were retrieved yielded >=2 different genotypes and/or
antimicrobial susceptibility profiles. Future studies should focus on the
seasonal and geographical variations of prevalence and diversity patterns of
clostridial species in small animals.
PMID- 28687281
TI - Head computed tomography for prognostication of poor outcome in comatose patients
after cardiac arrest and targeted temperature management.
AB - INTRODUCTION: A multimodal approach to prognostication of outcome after cardiac
arrest (CA) is recommended. Evidence for combinations of methods is low. In this
post-hoc analysis we described findings on head computed tomography (CT) after
CA. We also examined whether generalised oedema on CT alone or together with the
biomarker Neuron-specific enolase (NSE) could predict poor outcome. METHODS:
Patients participating in the Target Temperature Management after out-of-hospital
cardiac-arrest-trial underwent CT based on clinical indications. Findings were
divided into pre-specified categories according to local radiologists
descriptions. Generalised oedema alone and in combination with peak NSE at either
48h or 72h was correlated with poor outcome at 6 months follow-up using the
Cerebral Performance Category (CPC 3-5). RESULTS: 356/939 (37.9%) of patients
underwent head CT. Initial CT<=24h after CA was normal in 174/218 (79.8%), whilst
generalised oedema was diagnosed in 21/218 (9.6%). Between days 1-7, generalised
oedema was seen in 65/143 (45.5%), acute/subacute infarction in 27/143 (18.9%)
and bleeding in 9/143 (6.3%). Overall, generalised oedema predicted poor outcome
with 33.6% sensitivity (95%CI:28.1-39.5) and 98.4% specificity (95%CI:94.3-99.6),
whilst peak NSE demonstrated sensitivities of 61.5-64.8% and specificity 95.7%
(95%CI:89.5-98.4). The combination of peak NSE>38ng/l and generalised oedema on
CT predicted poor outcome with 46.0% sensitivity (95%CI:36.5-55.8) with no false
positives. NSE was significantly higher in patients with generalised oedema.
CONCLUSION: In this study, generalised oedema was more common >24h<=7d after CA.
The combination of CT and NSE improved sensitivity and specificity compared to CT
alone, with no false positives in this limited population.
PMID- 28687282
TI - Thinking differently about specialist imaging education.
PMID- 28687283
TI - Advanced and extended scope practice of diagnostic radiographers in Scotland:
Exploring strategic imaging service imperatives.
AB - INTRODUCTION: The development of diagnostic imaging services manifests features
specific to the Scottish environment, in particular development of the
radiographic workforce through implementing skills mix and role developments to
enhance outcomes for patients. A component of a College of Radiographers Industry
Partnership Scheme (CoRIPS) supported study, this research investigates
perspectives of strategic service managers with Health Board responsibility for
service delivery. METHOD: A questionnaire survey was administered to strategic
service managers across Scotland (N = 14), followed up with telephone interviews.
There was a return rate of 57% (n = 8) for the questionnaires and n = 4 agreed to
be interviewed. Data collected related to radiographer roles across their Board
area; awareness and understanding of service development issues and features as
well as perspective on opportunities and barriers in the context of Scottish
Government policy, workforce logistics, attitudes and inter-professional
relationships. RESULTS: The results indicate evidence of financial, logistical
and political barriers to service evolution, offset by a sense of optimism that
scope for beneficial change may be approaching. There are a range of significant
initiatives in place and an appetite exists to pursue the development of
radiographer roles and skill mix for the benefit of service users more generally.
CONCLUSION: The difficulties in achieving change are well understood and there
are basic issues related to finance and industrial relations. There are also
however, cultural elements to contend with in the form of attitudes demonstrated
by some radiographers and significantly, the radiological community whose
influence on the practice of independently regulated radiographers seems
incongruent.
PMID- 28687284
TI - Are English CT departments and radiographers prepared for the morbidly obese
patient?
AB - INTRODUCTION: Morbid obesity is increasing in England, as is the use of CT
scanning. All CT scanners have weight and body width limits. It is imperative
that the radiographer performing the scan is aware of these limits, particularly
in an emergency. This study aim was to determine whether radiographers are aware
of their scanner limits, where they may be able to send a patient who exceeds
these limits and whether a formal protocol exists. The secondary aim of the study
was to determine capacities of scanners in acute trusts throughout England.
METHODS: CT radiographers from 86 English Hospital Trusts with Emergency
Departments were contacted and asked questions regarding their CT scanners and
their practice of CT scanning morbidly obese patients. RESULTS: 21% of CT
radiographers did not know the maximum width capacity of their scanner. Only 24%
knew where a nearby larger capacity scanner was located and only 3% had a formal
protocol for scanning obese patients. Weight capacities ranged from 147 to 305
kg. Width capacities ranged from 55 to 100 cm. 70% had weight capacity 226 kg or
less and 70% had size capacity of 78 cm or less. CONCLUSION: Patients over 226 kg
or 78 cm may not be accommodated in most (70%) trusts in England. Lack of
knowledge of scanner capacities and alternative scanners for morbidly obese
patients could have consequences for these patients, particularly in an
emergency. The authors advise that all acute trusts have a protocol regarding CT
scanning morbidly obese to prevent delays in accessing imaging.
PMID- 28687285
TI - A JAFROC study of nodule detection performance in CT images of a thorax acquired
during PET/CT.
AB - PURPOSE: Two types of CT images (modalities) are acquired in PET/CT: for
attenuation correction (AC) and diagnosis. The purpose of the study was to
compare nodule detection and localization performance between these two
modalities. METHODS: CT images, using both modalities, of an anthropomorphic
chest phantom containing zero or more simulated spherical nodules of 5, 8, 10 and
12 mm diameters and contrasts -800, -630 and 100 HU were acquired. An observer
performance study using nine observers interpreting 45 normal (zero nodules)
images and 47 abnormal images (1-3 nodules; average 1.26) was conducted using the
free-response receiver operating characteristic (FROC) paradigm. Data were
analysed using an R software package implemented jackknife alternative FROC
(JAFROC) analysis. Both empirical areas under the equally weighted AFROC curve
(wAFROC) and under the highest rating inferred ROC (HR-ROC) curve were used as
figures of merit (FOM). To control the probability of Type I error test alpha was
set at 0.05. RESULTS: Nodule detection as measured by either FOM was
significantly better on the diagnostic quality images (2nd modality),
irrespective of the method of analysis, [reader averaged inter-modality wAFROC
FOM difference = -0.07 (-0.11,-0.04); reader averaged inter-modality HR-ROC FOM
difference = -0.05 (-0.09, -0.01)]. CONCLUSION: Nodule detection was
statistically worse on images acquired for AC; suggesting that images acquired
for AC should not be used to evaluate pulmonary pathology.
PMID- 28687286
TI - Compliance to Diagnostic Reference Levels for radiation exposure in common
radiological procedures in Dutch hospitals: A nation-wide survey carried out by
medical imaging students.
AB - INTRODUCTION: In the Netherlands, hospitals have difficulty in implementing the
formal procedure of comparing radiation dose values to Diagnostic Reference
Levels (DRLs). METHODS: To support the hospitals, train radiography students, and
carry out a nationwide dose survey, diagnostic radiography students performed 125
DRL comparisons for nine different procedures in 29 radiology departments.
Students were instructed at three Dutch Universities of Applied Sciences with a
radiography programme and supervised by medical physicists from the participating
hospitals. RESULTS: After a pilot study in the western part of the country in
eight hospitals, this study was enlarged to involve 21 hospitals from all over
the Netherlands. The 86 obtained dose comparisons fall below the DRLs in 97% of
all cases. This very high compliance may have been enhanced by the voluntary
participation of hospitals that are confident about their performance.
CONCLUSION: The results indicate that the current DRLs that were not based on a
national survey, may need to be updated, sometimes to half their current value.
For chest and pelvis examinations the DRLs could be lowered from 12 and 300
MUGy.m2 to the 75-percentile values found in this study of 5,9 and 188 MUGy.m2,
respectively.
PMID- 28687287
TI - Impact of CT parameters on the physical quantities related to image quality for
two MDCT scanners using the ACR accreditation phantom: A phantom study.
AB - INTRODUCTION: To evaluate the image quality provided by MDCT scanners using an
ACR phantom an to find out the relationship between CT parameters and physical
quantities related to image quality. METHODS: A GE Lightspeed VCT and a GE
Lightspeed Pro 16 are used. The ACR phantom consists of four modules for
evaluating physical parameters. The image quality parameters, such as CT number,
linearity, CNR, image uniformity, SNR and at least spatial resolution using MTF,
by different sets of image acquisition protocols (IAPs) are characterized. The
influences of the IAPs on the physical quantities are also discussed. RESULTS:
The CT numbers behaved linearly relative to material density for all tube
voltages. The impact of the tube current on the CT numbers is neglectable.
However, the variation of the tube current reflects in the CT number
uncertainties. The CNR are altered by changing the IAPs. 50% MTF decreases from
6.2 to 3.6 lp/cm and from 6.5 to 3.7 lp/cm using Lung and Soft kernel for the
Lightspeed VCT and Lightspeed Pro 16 scanner, respectively. CONCLUSION: The
dependence of the image quality parameters on reconstruction kernels, tube peak
voltages, tube currents and the slice thicknesses has been discussed. The tube
peak voltage has the most influence on the CT numbers. The results indicate that
the reconstruction kernel has the main impact on the spatial resolution. The
spatial resolution dependence on the tube voltages, tube currents and slice
thicknesses can be ignored.
PMID- 28687288
TI - Does collimation affect patient dose in antero-posterior thoraco-lumbar spine?
AB - INTRODUCTION: The purpose of this study is to determine the effect of collimation
on the lifetime attributable risk (LAR) of cancer incidence in all body organs
(effective risk) in patients undergoing antero-posterior (AP) examinations of the
spine. This is of particular importance for patients suffering from scoliosis as
in their case regular repeat examinations are required and also because such
patients are usually young and more susceptible to the effects of ionising
radiation than are older patients. METHODS: High sensitivity thermo-luminescent
dosimeters (TLDs) were used to measure radiation dose to all organs of an adult
male dosimetry phantom, positioned for an AP projection of the thoraco-lumbar
spine. Exposures were made, first applying tight collimation and then
subsequently with loose collimation, using the same acquisition factors. In each
case, the individual TLDs were measured to determine the local absorbed dose and
those representing each organ averaged to calculate organ dose. This information
was then used to calculate the effective risk of cancer incidence for each decade
of life from 20 to 80, and to compare the likelihood of cancer incidence when
using tight and loose collimation. RESULTS: The calculated figures for effective
risk of cancer incidence suggest that the risk when using loose collimation
compared to the use of tight collimation is over three times as high and this is
the case across all age decades from 20 to 80. CONCLUSION: Tight collimation can
greatly reduce radiation dose and risk of cancer incidence. However collimation
in scoliotic patients can be necessarily limited.
PMID- 28687289
TI - Occupational burnout among radiation therapists in Australia: Findings from a
mixed methods study.
AB - INTRODUCTION: Evidence demonstrates that health care professionals in the
palliative care context are more burned out than other health professionals. The
aims of this study were to examine: (1) occupational burnout levels among
radiation therapists in Australia, (2) association between demographic factors on
burnout and (3) radiation therapists' perceptions of burnout. METHODS: A cross
sectional online survey including the Maslach Burnout Inventory was administered
to Radiation Therapists in Australia. Data were analysed using SPSS Ver 20 and
open ended comments were analysed thematically using Nvivo 10. RESULTS: A total
of 200 radiation therapists participated in the survey. RTs had a high mean (+/
SD) burnout score for emotional exhaustion (38.5 +/- 8.2), depersonalisation
(17.5 +/- 4.7) and personal achievement (30.5.3 +/- 4.3) compared to RTs and
health workers in other studies. High levels of emotional exhaustion,
depersonalisation and low levels of personal achievement were present in 93%
(186/200), 87% (174/200) and 61% (122/200) of participants respectively. RTs
identified high workload and staff shortages, interpersonal conflict and
technology as key sources of stress in the RT work environment. CONCLUSION:
Australian RTs' level of burnout on all three stages of burnout exceed previously
reported burnout levels for similar cohorts both locally and internationally. It
is important that future interventions aimed at minimising or preventing
stressors are identified and implemented in the radiation therapy work
environment.
PMID- 28687290
TI - A pilot study investigating two dose reduction techniques for AP lumbar spine
radiography using direct dosimetry and Projection VR.
AB - INTRODUCTION: The purpose of this study was to compare radiation dose
measurements generated using a virtual radiography simulation with experimental
dosimeter measurements for two radiation dose reduction techniques in digital
radiography. METHODS: Entrance Surface Dose (ESD) measurements were generated for
an antero-posterior lumbar spine radiograph experimentally using NanoDOTTM,
single point dosimeters, for two radiographic systems (systems 1 and 2) and using
Projection VRTM, a virtual radiography simulation (system 3). Two dose reduction
methods were tested, application of the 15% kVp rule, or simplified 10 kVp rule,
and the exposure maintenance formula. The 15% or 10 kVp rules use a specified
increase in kVp and halving of the mAs to reduce patient ESD. The exposure
maintenance formula uses the increase in source-to-object distance to reduce ESD.
RESULTS: Increasing kVp from 75 to 96 kVp, with the concomitant decrease in mAs,
resulted in percent ESD reduction of 59.5% (4.02-1.63 mGy), 60.8% (3.55-1.39
mGy), and 60.3% (6.65-2.64 mGy), for experimental systems 1 and 2, and virtual
simulation (system 3), respectively. Increasing the SID (with the appropriate
increase in mAs) from 100 to 140 cm reduced ESD by 22.3% 18.8%, and 23.5%, for
experimental systems 1 and 2, and virtual simulation (system 3), respectively.
CONCLUSION: Percent dose reduction measurements were similar between the
experimental and virtual measurement systems investigated. For the dose reduction
practices tested, Projection VRTM provides a realistic alternate of percent dose
reduction to direct dosimetry.
PMID- 28687291
TI - Student radiographers' attitudes towards the older patient - A longitudinal
study.
AB - INTRODUCTION: To design, implement and evaluate the effect of an educational
intervention on student radiographer attitudes across their educational tenure.
METHODS: In the first phase, an educational intervention that involved didactic
lectures, reflective exercises and simulation suits, aimed at improving student
radiographer attitudes towards the older person, was designed and implemented.
Kogan's attitudes towards older people (KoP) scale was administrated at five test
points; pre-intervention; post-intervention; 6 months post intervention; 12
months post intervention and 24 months post intervention. At the final test point
these quantitative data was supplemented with qualitative data for triangulation
of the findings. RESULTS: Students held positive attitudes towards older people
pre intervention, these increased significantly post intervention (p = 0.01).
However, this increase in positive scores was not noted at 6 months and 12-months
post intervention. At 24-months post intervention, although there was a slight
increase in positive attitudes when compared to the 6 and 12 month scores, this
increase was not found to be significant (p = 0.178) CONCLUSION: The results post
intervention suggested that an educational intervention can have a significant
impact on student radiographer's attitudes towards older people. However, the
qualitative data suggests that experiences on initial clinical placement can be
detrimental to attitudinal scores, particularly if the intervention does not
include Dementia care strategies.
PMID- 28687292
TI - Mixed messages: An evaluation of NHS Trust Social Media policies in the North
West of England.
AB - INTRODUCTION: Despite National Health Service (NHS) information strategy
promoting the use of Social Media (SoMe) to encourage greater engagement between
service users and providers, a team investigating online SoMe interaction between
breast screening practitioners and clients found that practitioners alleged
discouragement from employers' policies. This study aimed to investigate whether
this barrier was genuine, and illuminate whether local policy differed from
national strategy. METHOD: The study used a qualitative grounded theory approach
to generate a theory. Nine policies from the North West of England were analysed.
A framework was derived from the data, and an analysis of policy tone followed by
a detailed coding of policy content was undertaken. Comparative analysis
continued by reviewing the literature, and a condensed framework revealed five
broad categories that policies addressed. RESULTS: The analysis revealed the
policies varied in content, but not in tone, which was mostly discouraging.
Coding the content revealed that the most frequently addressed point was that of
protecting the employers' reputation, and after further analysis, the resultant
condensed framework showed that policies were imbalanced and heavily skewed
towards Security, Conduct & Behaviour and Reputation. CONCLUSION: Practitioners
within breast screening services are discouraged by overly prohibitive and
prescriptive SoMe policies; with these varying tremendously in comprehensiveness,
but with a narrow focus on security and employers reputation; in contrast with
national strategy. Recommendations are that policy revision is undertaken with
consultation by more than one stakeholder, and SoMe training is offered for all
members of NHS staff.
PMID- 28687293
TI - Antero-posterior (AP) pelvis x-ray imaging on a trolley: Impact of trolley
design, mattress design and radiographer practice on image quality and radiation
dose.
AB - INTRODUCTION: Physical and technical differences exist between imaging on an x
ray tabletop and imaging on a trolley. This study evaluates how trolley imaging
impacts image quality and radiation dose for an antero-posterior (AP) pelvis
projection whilst subsequently exploring means of optimising this imaging
examination. METHODS: An anthropomorphic pelvis phantom was imaged on a
commercially available trolley under various conditions. Variables explored
included two mattresses, two image receptor holder positions, three source to
image distances (SIDs) and four mAs values. Image quality was evaluated using
relative visual grading analysis with the reference image acquired on the x-ray
tabletop. Contrast to noise ratio (CNR) was calculated. Effective dose was
established using Monte Carlo simulation. Optimisation scores were derived as a
figure of merit by dividing effective dose with visual image quality scores.
RESULTS: Visual image quality reduced significantly (p < 0.05) whilst effective
dose increased significantly (p < 0.05) for images acquired on the trolley using
identical acquisition parameters to the reference image. The trolley image with
the highest optimisation score was acquired using 130 cm SID, 20 mAs, the
standard mattress and platform not elevated. A difference of 12.8 mm was found
between the image with the lowest and highest magnification factor (18%).
CONCLUSION: The acquisition parameters used for AP pelvis on the x-ray tabletop
are not transferable to trolley imaging and should be modified accordingly to
compensate for the differences that exist. Exposure charts should be developed
for trolley imaging to ensure optimal image quality at lowest possible dose.
PMID- 28687294
TI - An exploration of mammographers' attitudes towards the use of social media for
providing breast screening information to clients.
AB - INTRODUCTION: Increasingly patients and clients of health services are using
social media to locate information about medical procedures and outcomes. There
is increasing pressure for health professionals to engage in on-line spaces to
provide clear and accurate information to their patient community. Research
suggests there are some anxieties on the part of practitioners to do this. This
study aimed to explore the attitudes of the NHS breast screening programme
workforce towards engaging in online discussions with clients about breast
screening. METHOD: 78 practitioners, representing a range of professional roles
within the NHS Breast Screening Programme, attended one of 4 workshops. We used a
Nominal Group Technique to identify and rank responses to the question: "What are
the challenges that practitioners face in using SoME as part of their role?"
Responses were categorised into themes. Participants were also asked to identify
solutions to these challenges. RESULTS: Challenges: We identified two overarching
themes: (1) Working within boundaries: which was further categorised into (a)
Professional/legal accountability; (b) Information accuracy and (c)Time as a
boundary, and (2) Support: further categorised into (a) Employer and (b) Manager.
Solutions: These included: training in technical and interactional aspects of on
line communication and a responsibility to better understand employer and
professional body SoMe policies. CONCLUSION: The study participants appeared
willing and motivated to engage in SoMe. However, in keeping with the literature
from other disciplines, a number of challenges need to be overcome for its use to
be adopted more widely by breast screening professionals.
PMID- 28687295
TI - Attitudes of oncology healthcare practitioners towards smoking cessation: A
systematic review of the facilitators, barriers and recommendations for delivery
of advice and support to cancer patients.
AB - OBJECTIVES: A systematic review of the literature was conducted. The review was
conducted using a search of the literature for all years up to October 2016.
Statements that identified facilitators, barriers or recommendations surrounding
smoking cessation delivery were extracted and analogous statements aggregated to
enable thematic analysis. After searching multiple databases and the application
of exclusion and inclusion criteria, a total of 19 acceptable studies were
identified. KEY FINDINGS: Delivery of cessation by oncology professionals was
impacted by their own knowledge and views, their perception of the benefits to
patient health and by the workplace procedures within their institution.
CONCLUSION: Oncology practitioners worldwide face similar issues in delivering
smoking cessation advice. By improving training programs that address the
attitudes and beliefs which facilitate or block delivery of smoking cessation and
by implementing systemic changes within cancer centres, delivery of smoking
cessation should be enabled.
PMID- 28687296
TI - Letter to the Editor.
PMID- 28687297
TI - Response to letter by Faisal Alrehily.
PMID- 28687298
TI - Response letter by Scottish students to the RCR position statement: The radiology
crisis in Scotland: Sustainable solutions are needed now.
PMID- 28687299
TI - Letter to the Editor.
PMID- 28687300
TI - A response to a Letter to the Editor re: Improving Continuing Professional
Development opportunities for radiographers: A single centre evaluation.
PMID- 28687301
TI - Reproducibility of ultrasound-derived muscle thickness and echo-intensity for the
entire quadriceps femoris muscle.
AB - INTRODUCTION: Muscle thickness (MT) and muscle echo-intensity (EI) allow the
study of skeletal muscle adaptive changes with ultrasound. This study
investigates the intra- and inter-session reliability and agreement of MT and EI
measurements for each of the four heads of the quadriceps femoris in transverse
and longitudinal scans, using two sizes for the region of interest (ROI); EI
measurements only. METHODS: Three B-mode images from two views were acquired from
each head of quadriceps femoris from twenty participants (10 females) in two
sessions, 7 days apart. EI was measured using a large and a small ROI.
Reliability was examined with the mixed two-way intra-class correlation
coefficient (ICC), the standard error of mean (SEM) and the smallest detectable
change (SDC). Bland-Altman's plots were used to study agreement. RESULTS: High to
very high inter-session ICC values were found for MT for all muscle heads,
particularly for measurements from transverse scans. For EI measurement, ICC
values ranged from low to high, with higher ICC values seen with the largest ROI.
SDC values ranged between 0.19 and 0.53 cm for MT and between 3.73 and 18.56
arbitrary units (a.u.) for two ROIs. Good agreement existed between MT
measurements made in both scans. A small bias and larger 95% limits of agreement
were seen for EI measurements collected with the two ROI sizes. CONCLUSION:
Ultrasound measures of MT and EI show moderate to very high reliability. The
reliability and agreement of MT and EI measurements are improved in transverse
scans and with larger ROIs.
PMID- 28687302
TI - Spontaneous gastric rupture after Sodium Bicarbonate consumption: A case report.
AB - Spontaneous gastric rupture is a rare condition however a prompt diagnosis and
treatment are necessary to decrease mortality and morbidity. We report a case of
stomach rupture after the ingestion of Sodium Bicarbonate (SB); imaging findings
with a brief review of the literature are presented.
PMID- 28687303
TI - Atypical image findings in a primary subcutaneous hydatid cyst in the gluteal
area.
PMID- 28687304
TI - Superior shoulder suspensory complex fracture dislocation case report.
AB - BACKGROUND: Acromioclavicular joint dislocation can be more complex than it first
appears. The presented case had an unusual combination of injuries to the
superior shoulder suspensory complex, which yielded some interesting learning
points. CASE SUMMARY: The injuries were sustained after a fall from a push bike
and included acromioclavicular dislocation with coracoid process, clavicle and
acromion process fractures. These were identified on the initial X-ray
examination, which was followed by computed tomography for surgical planning. The
injuries were successfully treated by internal fixation. CONCLUSION: The
unexpected complexity of the injuries could have led to subtle but important
findings being overlooked. This case highlights the importance of a thorough
search strategy, consideration of injury biomechanics and knowledge of associated
injuries.
PMID- 28687305
TI - Incidental finding of a monostotic form of Paget Disease of the scapula in a lung
cancer patient.
AB - Paget Disease of the bone is a metabolic disorder which leads to a profound
alteration of the bone's architecture. It may be asymptomatic and, since its
radiological features mimic those of bone metastases, may present a diagnostic
dilemma during the evaluation of a cancer patient. We illustrate an uncommon
monostotic form of the disease, affecting solely the scapula, diagnosed during
the staging of a lung cancer patient.
PMID- 28687307
TI - Altered neurobiological function of brainstem hypoglossal neurons in
DiGeorge/22q11.2 Deletion Syndrome.
AB - DiGeorge/22q11.2 Deletion Syndrome (22q11DS) is a common genetic microdeletion
syndrome that underlies several neurodevelopmental disorders including autism,
attention deficit/hyperactivity disorder, and schizophrenia. In addition to
cognitive impairments, those with 22q11DS have disrupted feeding and swallowing
from birth onward. This perinatal dysphagia significantly compromises nutritional
status, impairs appropriate weight gain, and can lead to life threatening
aspiration-based infections. Appropriately timed excitation and inhibition of
brainstem hypoglossal motor neurons, which innervate tongue muscles, is essential
for proper feeding and swallowing. In this study we have examined changes in
hypoglossal motor neuron function in the LgDel mouse model of 22q11DS.
Hypoglossal motor neurons from LgDel mouse pups have action potentials with
afterhyperpolarizations, mediated by a large conductance charybdotoxin-sensitive
Ca-activated K current, that are significantly shorter in duration and greater in
magnitude than those in wild-type pups. In addition, the amplitude, but not
frequency, of glutamatergic excitatory glutamatergic postsynaptic currents
(EPSCs) is diminished, and GABAergic, but not glycinergic, neurotransmission to
hypoglossal motor neurons was reduced in LgDel animals. These observations
provide a foundation for understanding the neurological changes in hypoglossal
motor neuron function and their contribution to swallowing abnormalities that
occur in DiGeorge/22q11.2 Deletion Syndrome.
PMID- 28687306
TI - Auditory and Visual Sequence Learning in Humans and Monkeys using an Artificial
Grammar Learning Paradigm.
AB - Language flexibly supports the human ability to communicate using different
sensory modalities, such as writing and reading in the visual modality and
speaking and listening in the auditory domain. Although it has been argued that
nonhuman primate communication abilities are inherently multisensory, direct
behavioural comparisons between human and nonhuman primates are scant. Artificial
grammar learning (AGL) tasks and statistical learning experiments can be used to
emulate ordering relationships between words in a sentence. However, previous
comparative work using such paradigms has primarily investigated sequence
learning within a single sensory modality. We used an AGL paradigm to evaluate
how humans and macaque monkeys learn and respond to identically structured
sequences of either auditory or visual stimuli. In the auditory and visual
experiments, we found that both species were sensitive to the ordering
relationships between elements in the sequences. Moreover, the humans and monkeys
produced largely similar response patterns to the visual and auditory sequences,
indicating that the sequences are processed in comparable ways across the sensory
modalities. These results provide evidence that human sequence processing
abilities stem from an evolutionarily conserved capacity that appears to operate
comparably across the sensory modalities in both human and nonhuman primates. The
findings set the stage for future neurobiological studies to investigate the
multisensory nature of these sequencing operations in nonhuman primates and how
they compare to related processes in humans.
PMID- 28687308
TI - Deep hypothermia therapy attenuates LPS-induced microglia neuroinflammation via
the STAT3 pathway.
AB - Deep hypothermia therapy (HT) is a standard method for neuroprotection during
complex pediatric cardiac surgery involving extracorporeal circulation and deep
hypothermic cardiac arrest. The procedure, however, can provoke systemic
inflammatory response syndrome (SIRS), one of the most severe side effects
associated with pediatric cardiac surgery. To date, the cellular inflammatory
mechanisms induced by deep HT remain to be elucidated. Therefore, we investigated
the effects of deep HT (17 degrees C) and rewarming on the inflammatory response
in lipopolysaccharide (LPS) stimulated BV-2 murine microglia. Additionally, we
also investigated the application of Stattic, a signal transducer and activator
of transcription 3 (STAT3) activation inhibitor, as an alternative to physical
cooling to attenuate the LPS-induced inflammatory response. Deep HT had no
cytotoxic effect but attenuated microglia migration. IkappaBalpha degradation was
delayed by deep HT resulting in the attenuation of pNF-kappaB p65 migration into
the nucleus and significant decreases in pro-inflammatory IL-6, TNF-alpha, and
MCP-1 expressions and secretions, as well as decreased anti-inflammatory IL-10
and SOCS3 expressions. Additionally, pStat3 was significantly down regulated
under deep hypothermic conditions, also corresponding with the significant
reduction in IL-6 and TNF-alpha expressions. Similar to the effects of HT, the
application of Stattic under normothermic conditions resulted in significantly
reduced IL-6 and TNF-alpha expressions. Moreover, attenuation of the inflammatory
response resulted in decreased apoptosis in a direct co-culture of microglia and
neurons. HT reduces the inflammatory response in LPS-stimulated BV-2 microglial
cells, alluding to a possible mechanism of therapeutic hypothermia-induced
neuroprotection. In the future, attenuating the phospho-STAT3 pathway may lead to
the development of a neuroprotectant with greater clinical efficacy.
PMID- 28687309
TI - Reduced axonal diameter of peripheral nerve fibers in a mouse model of Rett
syndrome.
AB - Rett syndrome (RTT) is a neurological disorder characterized by motor and
cognitive impairment, autonomic dysfunction and a loss of purposeful hand skills.
In the majority of cases, typical RTT is caused by de novo mutations in the X
linked gene, MECP2. Alterations in the structure and function of neurons within
the central nervous system of RTT patients and Mecp2-null mouse models are well
established. In contrast, few studies have investigated the effects of MeCP2
deficiency on peripheral nerves. In this study, we conducted detailed
morphometric as well as functional analysis of the sciatic nerves of symptomatic
adult female Mecp2+/- mice. We observed a significant reduction in the mean
diameter of myelinated nerve fibers in Mecp2+/- mice. In myelinated fibers,
mitochondrial densities per unit area of axoplasm were significantly altered in
Mecp2+/- mice. However, conduction properties of the sciatic nerve of Mecp2
knockout mice were not different from control. These subtle changes in myelinated
peripheral nerve fibers in heterozygous Mecp2 knockout mice could potentially
explain some RTT phenotypes.
PMID- 28687310
TI - Structural and functional disorders of hippocampus following ischemia/reperfusion
in lower limbs and kidneys.
AB - Recent evidence suggests that ischemia/reperfusion (I/R) in an organ may have
distance effect on the brain. In this study, the effects of renal I/R, limb I/R
or both together on the structural and function of hippocampus were evaluated and
compared. Hence, rats were subjected to 2-h bilateral lower limb ischemia, 45-min
bilateral renal ischemia, or combined limb and renal ischemia followed by 1-day
reperfusion. At 22-h reperfusion, each rat was fixed on a stereotaxic apparatus
for performing electrophysiological study on the hippocampus. The long-term
potentiation (LTP) was induced by high-frequency stimulation (HFS), and paired
pulse ratio (PPR) was also monitored before and after HFS delivery. After taking
blood sample and sacrificing animal, its brain was removed and preserved for
stereological study. The limb I/R reduced plasma osmolality that led to synaptic
excitement in the hippocampus, where there was a considerable loss of pyramidal
cells and markedly impaired short- and long-term synaptic plasticity. The renal
I/R largely increased plasma creatinine that might excite basal synaptic
transmission. In the rats with combined limb and renal I/R, the hippocampal
neuronal loss and impaired synaptic plasticity were the same as those with limb
I/R, but basal synaptic transmission was lowered. In conclusion, the 2-h lower
limb ischemia compared to 45-min renal ischemia induced more injurious distant
effects on the hippocampus after 1-day reperfusion. The combination of renal and
limb I/R did not add or potentiate hippocampal neuronal loss and synaptic
plasticity impairment, whereas it decreased the basal synaptic transmission with
respect to each one alone.
PMID- 28687311
TI - Selective changes in locomotor activity in mice due to low-intensity microwaves
amplitude modulated in the EEG spectral domain.
AB - Despite the numerous benefits of microwave applications in our daily life,
microwaves were associated with diverse neurological complaints such as headaches
and impaired sleep patterns, and changes in the electroencephalogram (EEG). To
which extent microwaves influence the brain function remains unclear. This
exploratory study assessed the behavior and neurochemistry in mice immediately or
4weeks after a 6-day exposure to low-intensity 10-GHz microwaves with an
amplitude modulation (AM) of 2 or 8Hz. These modulation frequencies of 2 and 8Hz
are situated within the delta and theta-alpha frequency bands in the EEG spectrum
and are associated with sleep and active behavior, respectively. During these
experiments, the specific absorbance rate was 0.3W/kg increasing the brain
temperature with 0.23 degrees C. For the first time, exposing mice to 8-Hz AM
significantly reduced locomotor activity in an open field immediately after
exposure which normalized after 4weeks. This in contrast to 2-Hz AM which didn't
induce significant changes in locomotor activity immediately and 4weeks after
exposure. Despite this difference in motor behavior, no significant changes in
striatal dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC) levels and
DOPAC/DA turnover nor in cortical glutamate (GLU) concentrations were detected.
In all cases, no effects on motor coordination on a rotarod, spatial working
memory, anxiety nor depressive-like behavior were observed. The outcome of this
study indicates that exposing mice to low-intensity 8-Hz AM microwaves can alter
the locomotor activity in contrast to 2-Hz AM which did not affect the tested
behaviors.
PMID- 28687312
TI - Direction of commissural axon projections in different regions of the spinal cord
during chicken embryonic development.
AB - Few researchers have investigated the direction of commissural axon projections
on the contralateral side of the vertebrate embryonic spinal cord, especially for
comparison between its different regions. In this study, pCAGGS-GFP plasmid
expression was limited to different regions of the chicken embryonic spinal cord
(cervical, anterior limb, anterior thorax, posterior thorax and posterior limb)
at E3 using in ovo electroporation with modified electrodes and optimal
electroporation conditions. Then open-book technique was performed at E6 to
analyze the direction of axon projections in different spinal cord regions. The
results show that in the five investigated regions, most axons projected
rostrally after crossing the floor plate while a minority projected caudally. And
there was a significant difference between the rostral and caudal projection
quantities (P<0.01). The ratio of rostral and caudal projections was
significantly different between the five investigated regions (P<0.05), except
between the cervical region and the anterior limb (P>0.05). The projections were
most likely to be rostral for the posterior limb followed by the posterior
thorax, cervical region, anterior limb and anterior thorax. Our data for the
direction of the commissural axon projections will be helpful in the future
analyses of axon projection mechanisms and spinal cord-brain circuit formation.
PMID- 28687314
TI - Participation of the peripheral taste system in aging-dependent changes in taste
sensitivity.
AB - Previous studies have shown that aging modifies taste sensitivity. However, the
factors affecting the changes in taste sensitivity remain unclear. To investigate
the cause of the age-related changes in taste sensitivity, we compared the
peripheral taste detection systems in young and old mice. First, we examined
whether taste sensitivity varied according to age using behavioral assays. We
confirmed that the taste sensitivities to salty and bitter tastes decreased with
aging. In other assays, the gustatory nerve responses to salty and sweet tastes
increased significantly with aging, while those to bitter taste did not change.
Thus, the profile of the gustatory nerve responses was inconsistent with the
profile of the behavioral responses. Next, we evaluated the expressions of taste
related molecules in the taste buds. Although no apparent differences in the
expressions of representative taste receptors were observed between the two age
groups, the mRNA expressions of signaling effectors were slightly, but
significantly, decreased in old mice. No significant differences in the turnover
rates of taste bud cells were observed between the two age groups. Thus, we did
not observe any large decreases in the expressions of taste-related molecules and
turnover rates of taste bud cells with aging. Based on these findings, we
conclude that changes in taste sensitivity with aging were not caused by aging
related degradation of peripheral taste organs. Meanwhile, the concentrations of
several serum components that modify taste responses changed with age. Thus,
taste signal-modifying factors such as serum components may have a contributing
role in aging-related changes in taste sensitivity.
PMID- 28687313
TI - Two different mirror neuron networks: The sensorimotor (hand) and limbic (face)
pathways.
AB - The vast majority of functional studies investigating mirror neurons (MNs)
explored their properties in relation to hand actions, and very few investigated
how MNs respond to mouth actions or communicative gestures. Since hand and mouth
MNs were recorded in two partially overlapping sectors of the ventral precentral
cortex of the macaque monkey, there is a general assumption that they share a
same neuroanatomical network, with the parietal cortex as a main source of visual
information. In the current review, we challenge this perspective and describe
the connectivity pattern of mouth MN sector. The mouth MNs F5/opercular region is
connected with premotor, parietal areas mostly related to the somatosensory and
motor representation of the face/mouth, and with area PrCO, involved in
processing gustatory and somatosensory intraoral input. Unlike hand MNs, mouth
MNs do not receive their visual input from parietal regions. Such information
related to face/communicative behaviors could come from the ventrolateral
prefrontal cortex. Further strong connections derive from limbic structures
involved in encoding emotional facial expressions and motivational/reward
processing. These brain structures include the anterior cingulate cortex, the
anterior and mid-dorsal insula, orbitofrontal cortex and the basolateral
amygdala. The mirror mechanism is therefore composed and supported by at least
two different anatomical pathways: one is concerned with sensorimotor
transformation in relation to reaching and hand grasping within the traditional
parietal-premotor circuits; the second one is linked to the mouth/face motor
control and is connected with limbic structures, involved in
communication/emotions and reward processing.
PMID- 28687315
TI - NADPH oxidase contributes to streptozotocin-induced neurodegeneration.
AB - Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the
progressive loss of memory. The neurodegeneration induced by AD has been linked
to oxidative damage. However, little is known about the involvement of NADPH
oxidase 2 (Nox2), a multisubunit enzyme that catalyzes the reduction of oxygen to
produce reactive oxygen species, in the pathogenesis of AD. The main purpose of
this study was to investigate the involvement of Nox2 in memory, in AD-related
brain abnormalities, oxidative damage, inflammation and neuronal death in the
hippocampus in the streptozotocin (STZ)-induced AD-like state by comparing the
effects of that drug on mice lacking gp91phox-/- and wild-type (Wt) mice. Nox2
gene expression was found increased in Wt mice after STZ injection. In object
recognition test, Wt mice injected with STZ presented impairment in short- and
long-term memory, which was not observed following Nox2 deletion. STZ treatment
induced increased phosphorylation of Tau and increased amyloid-beta, apoptosis
inducing factor (AIF) and astrocyte and microglial markers expression in Wt mice
but not in gp91phox-/-. STZ treatment increased oxidative damage and pro
inflammatory cytokines' release in Wt mice, which was not observed in gp91phox-/-
mice. Nox2 deletion had a positive effect on the IL-10 baseline production,
suggesting that this cytokine might contribute to the neuroprotection mechanism
against STZ-induced neurodegeneration. In summary, our data suggest that the Nox2
dependent reactive oxygen species (ROS) generation contributes to the STZ-induced
AD-like state.
PMID- 28687316
TI - Levodopa (L-DOPA) attenuates endoplasmic reticulum stress response and cell death
signaling through DRD2 in SH-SY5Y neuronal cells under alpha-synuclein-induced
toxicity.
AB - Parkinson's disease (PD) is characterized by the formation of Lewy bodies (LBs)
in dopaminergic neurons. alpha-Synuclein (alpha-syn), a major protein component
of LBs, is known to regulate synaptic plasticity, with a crucial role in memory
and motor function in the central nervous system. Levodopa (L-3,4
dihydroxyphenylalanine; also known as L-DOPA) is considered the most effective
medication for controlling the symptoms of PD. However, it is unclear whether L
DOPA improves the neuropathology of PD. In the present study, we investigated the
effect of L-DOPA on SH-SY5Y neuronal cells under alpha-syn-induced toxicity. We
assessed the protein and mRNA levels of endoplasmic reticulum (ER) stress and
cell death markers using western blot analysis and reverse transcription-PCR. Our
data showed that L-DOPA could attenuate ER stress markers, including the levels
of activating transcription factor 4 (ATF4), C/EBPhomologous protein expression
(CHOP), immunoglobulin-heavy-chain-binding protein (BiP), sliced X-box-binding
protein 1 (XBP-1), and reduce nuclear factor kappa-light-chain-enhancer of
activated B cells (NF-kappaB) signaling through dopamine receptor D2 (DRD2) in SH
SY5Y neuronal cells under alpha-syn-induced toxicity. In conclusion, we suggest
that L-DOPA may attenuate the neuropathology of PD by regulating signaling
related to DRD2 in neuronal cells under alpha-syn-induced toxicity. Our study,
therefore, indicates an additional role for L-DOPA in the treatment of PD.
PMID- 28687317
TI - Effect of Soft Braces on Pain and Physical Function in Patients With Knee
Osteoarthritis: Systematic Review With Meta-Analyses.
AB - OBJECTIVES: To systematically review and synthesize the effects of soft braces on
pain and on self-reported and performance-based physical function in patients
with knee osteoarthritis. DATA SOURCES: The following electronic databases were
searched from inception to April 20, 2016: The Cochrane Central Register of
Controlled Trials (CENTRAL), PubMed, EMBASE, CINAHL, SPORTDiscus, Web of Science,
and PEDro. STUDY SELECTION: Randomized controlled trials (RCTs) and nonrandomized
controlled trials (non-RCTs), such as controlled clinical trials, crossover
studies, and case-control studies, were included. Two reviewers independently
screened articles and determined inclusion through predefined criteria. DATA
EXTRACTION: Data related to participant demographics, study design and methods,
interventions, and outcomes, including numerical means and SDs, were extracted by
1 reviewer. Methodological quality assessment was independently performed by 2
reviewers. DATA SYNTHESIS: Eleven studies were identified, including 6 RCTs and 5
non-RCTs. The methodological quality of included RCTs was low. There was a
moderate improvement in pain (standardized mean difference [SMD]=.52; 95%
confidence interval [CI], .14-.89; P=.007; 284 participants) in favor of wearing
a brace compared with not wearing a brace for the immediate, within-group
comparison. There was a moderate improvement in pain (SMD=.61; 95% CI, .33-.89;
P<.001; 206 participants) and a small to moderate improvement in self-reported
physical function (SMD=.39; 95% CI, .11-.67; P=.006; 206 participants) in favor
of patients receiving a soft brace versus standard care for the prolonged effect,
between-group comparison. CONCLUSIONS: Currently available evidence indicates
that soft braces have moderate effects on pain and small to moderate effects on
self-reported physical function in knee osteoarthritis. These findings highlight
the importance of soft braces as a technique to improve pain and physical
function in both the short- and long-term. Additional high-quality studies are
warranted to improve confidence in the findings.
PMID- 28687318
TI - Validation of the Participation Measure-3 Domains, 4 Dimensions (PM-3D4D).
AB - OBJECTIVE: To examine the construct validity of the Participation Measure-3
Domains, 4 Dimensions (PM-3D4D), a multidimensional participation measure
developed for use in rehabilitation practice. DESIGN: Cross-sectional study.
SETTING: Outpatient rehabilitation programs. PARTICIPANTS: Rehabilitation
patients (N=556; mean age, 61.4+/-23.6y; 47.1% women). INTERVENTIONS: Not
applicable. MAIN OUTCOME MEASURES: The PM-3D4D is a 19-item measure designed to
evaluate participation in 3 domains-Productivity, Social, and Community-across 4
dimensions-Diversity, Frequency, Desire for change, and Difficulty.
Intercorrelations among the 4 dimensions of the PM-3D4D and correlations between
the PM-3D4D and 3 legacy instruments-Participation Assessment with Recombined
Tools-Objective, Participation Measure for Post-Acute Care, and Satisfaction With
Life Scale-were examined to establish the convergent and divergent validity of
the PM-3D4D. Known-group validity was evaluated by comparing PM-3D4D scores
across age groups and groups of people classified by functional level. RESULTS:
The Diversity scale of the PM-3D4D was strongly correlated with the Frequency
scale (Spearman correlation coefficient, rs=.83-.96 across the 3 domains), and
these 2 scales showed moderate to strong correlations with the Difficulty scale
(rs=.42-.70) but weak (rs=-.4 to 0) and insignificant correlations with the
Desire for change scale. The Frequency and Difficulty scales of the PM-3D4D
showed moderate to strong correlations with the Participation Assessment with
Recombined Tools-Objective and Participation Measure for Post-Acute Care (rs=.41
.82), respectively, and the Desire for change scale had weak correlations with
the Satisfaction With Life Scale (rs=-.32 to -.18). Significant differences in PM
3D4D scores were found by age and functional level. CONCLUSIONS: Findings of this
study support the construct validity of the PM-3D4D, providing evidence for using
the PM-3D4D to assess rehabilitation patients' participation performance and
helping practitioners identify intervention priorities to improve patients'
participation outcomes.
PMID- 28687319
TI - Do the Findings of Magnetic Resonance Imaging, Arthrography, and Ultrasonography
Reflect Clinical Impairment in Patients With Idiopathic Adhesive Capsulitis of
the Shoulder?
AB - OBJECTIVE: To investigate the correlation between arthrography, magnetic
resonance imaging (MRI), and ultrasonography (US) findings in patients with
idiopathic adhesive capsulitis (IAC) of the shoulder and their clinical
presentation as well as functional impairment. DESIGN: Cross-sectional
observational study. SETTING: Institutional practice. PARTICIPANTS: Patients
(N=75) with a clinical diagnosis of unilateral IAC. INTERVENTIONS: Contrast
enhanced MRI, single-contrast arthrography, and US were performed in all
patients. MAIN OUTCOME MEASURES: The thickness of the axillary recess,
coracohumeral ligament (CHL), and enhanced portion in the rotator cuff interval
was measured using MRI. Arthrography was used to calculate the total score of
shoulder arthrographic criteria. US was used to measure the thickness of the
inferior glenohumeral ligament (IGHL) and CHL, and the IGHL ratio and CHL ratio
were calculated by comparing those of the unaffected side. RESULTS: None of the
MRI parameters was correlated with clinical assessment scores. The total score of
shoulder arthrographic criteria was negatively correlated with passive range of
motion of the total shoulder motion (P<.05), shoulder forward flexion (P<.05),
and abduction (P<.05). The total Constant-Murley score was well correlated with
the total score of shoulder arthrographic criteria (P<.05). The total shoulder
joint space capacity was positively correlated with passive range of motion of
the total shoulder motion (P<.05) and shoulder forward flexion (P<.05). The IGHL
thickness, IGHL ratio, CHL thickness, and CHL ratio were negatively correlated
with shoulder external rotation (P<.05). CONCLUSIONS: The findings of
arthrography and US in patients with IAC of the shoulder were correlated with
clinical assessment scores, whereas all measuring parameters on MRI were not. US
is recommended as the preferred option for diagnosing IAC of the shoulder because
it is noninvasive, reflects the clinical features of IAC, and provides anatomical
accuracy.
PMID- 28687321
TI - In vitro antibiofilm efficacy of Piper betle against quorum sensing mediated
biofilm formation of luminescent Vibrio harveyi.
AB - Vibrio harveyi is a potent biofilm former, which confers resistance to multiple
antimicrobials, disinfectants, chemicals and biocides. The prevalence of biofilm
mediated antibiotic resistance among aquatic bacterial pathogens stresses the
search for novel alternative approach to treat vibriosis in aquaculture.
Exploring suitable therapeutics from natural resources could be a novel area of
research. Therefore, this work was executed to evaluate the inhibitory effect of
Piper betle ethyl acetate extract (PBE) on bioluminescence production and biofilm
formation of V. harveyi. Minimal inhibitory concentration (MIC) of PBE against
planktonic V. harveyi was found to be 1600 MUg ml-1; furthermore, PBE inhibited
the quorum sensing (QS) mediated bioluminescence production and biofilm formation
in V. harveyi upto 98 and 74% respectively, at its sub-MIC concentration of 400
MUg ml-1 without affecting their cell viability. Similar results were obtained
for exopolysaccharides production and swimming motility related to biofilm
formation of V. harveyi, where PBE reduced EPS production upto 64%. Light and
confocal laser scanning microscopic analyses further confirmed that the PBE
effectively prevented the initial attachment as well as microcolonies formation
of V. harveyi biofilm, when compared to their untreated controls. This study
demonstrates the promising antibiofilm activity of PBE and confirms the
ethnopharmacological potential of this plant against V. harveyi infections.
PMID- 28687320
TI - Vancomycin-induced biofilm formation by methicillin-resistant Staphylococcus
aureus is associated with the secretion of membrane vesicles.
AB - Chronic burn wound infections caused by Stapyhylococcus aureus (S. aureus) are
largely associated with biofilm formation. However, the mechanism by which S.
aureus form biofilm in clinical environments is far less understood. In the
present study we addressed the association between biofilm formation and membrane
vesicle (MV) secretion of S. aureus during vancomycin treatment. A representative
methicillin-resistant S. aureus (MRSA) strain BWMR22 obtained from a chronic burn
wound was used in this study. Transmission electron microscope was used to
observe the MV secretion. Fourier transform infrared spectroscopy was used to
analyze the chemical component of MV. Biofilm formation was assayed under
conditions of sub-inhibitory concentrations of vancomycin. Functional potencies
of MV in surface adhesion and auto-aggregation were assayed in the presence of
additional purified MVs. Biofilm formation by S. aureus BWMR22 was enhanced in
the presence of sub-inhibitory concentration of vancomycin. Vancomycin treatment
caused an increase in the chemical composition of protein relative to
carbohydrates of secreted MVs, a property which was highly associated with
bacterial hydrophobicity, surface adhesion, and intercellular aggregation. These
findings suggest that MV secretion is correlated with biofilm formation by MRSA
especially under clinical conditions with improper vancomycin chemotherapy. This
study first demonstrates a potential role of MVs in the biofilm formation by S.
aureus, stresses on the importance of avoiding low dose of antibiotic therapy in
controlling of S. aureus infections, and provides further information to reveal
the mechanisms behind MRSA infections.
PMID- 28687322
TI - Chemically modified tetracyclines an emerging host modulator in chronic
periodontitis patients: A randomized, double-blind, placebo-controlled, clinical
trial.
AB - Although periodontal diseases are caused by some of the specific pathogens, most
of the tissue damage is caused by the host reaction to disease and not actually
by the infections. Therefore, host modulatory therapy (HMT) has advanced benefit
for the treatment of periodontitis, which works basically by reducing tissue
destruction and regeneration in periodontium by altering the critical aspects of
host response regulation and up regulating defensive regenerative responses. The
present study was conducted with the goal to test an innovative therapeutic
option using chemically modified tetracycline in patients affected with
generalized, moderate and severe chronic periodontitis. We assumed that CMT might
have the potential to provoke an assessable clinical result and pharmacologically
impede the level inflammatory flow. CMT (incyclinide) treated group had
significantly higher CAL (clinical attachment) values than Placebo Control
suggesting an improved CAL in CMT treatment. Host modulation therapy width
incyclinide can be as an adjunct to conventional nonsurgical therapies without
antimicrobial resistance. Progress was noticed in the clinical parameters but not
the serum CRP level in our study establishing the role of CMTs in controlling
chronic periodontitis. Also CMT treatment indicates its role in anti-inflammatory
process as it inhibited IL-12 and TNF alpha but IL-10 level was not affected.
However, more randomized placebo-controlled clinical trials with large sample
size are required in order to authenticate the usage of CMTs in chronic
periodontitis treatment. Based on this understanding, exploration of the novel,
low-cost synthetic inhibitors that can be used as potential therapeutic agents,
has been tested.
PMID- 28687323
TI - Electrophoretic pattern of glutathione S-transferase (GST) in antibiotic
resistance Gram-positive bacteria from poultry litter.
AB - The present study is aimed to assess the role of glutathione S-transferase (GST)
in antibiotic resistance among the bacteria isolated from the poultry litter and
to identify the effect of GST to reduce the antimicrobial activity of
antibiotics. Induction of various antibiotics to Staphylococcus, Streptococcus
and Micrococcus sp. isolated from the poultry litter showed that the activity of
GST was three to four folds higher than those of control. Analysis of the isozyme
pattern of GST revealed that variation in the expression may be due to antibiotic
resistance. The results concluded that GST might play an important role in the
protection against the toxic effect of the antimicrobial agents which leads
bacteria to become resistant to antibiotics.
PMID- 28687324
TI - In vitro antiviral efficacy of caffeic acid against canine distemper virus.
AB - Canine distemper (CD) is a highly contagious disease caused by the canine
distemper virus (CDV), and mortality can be as high as 100%. However, there is no
specific treatment for CD. In this study, the antiviral activity of the caffeic
acid against CDV was evaluated in vitro. The results showed that the IC50 of the
caffeic acid against CDV at 1 and 2 h post infection (PI) is 23.3 and 32.3
MUg/mL, respectively. Consistently, at 1 and 2 h PI, the caffeic acid exhibited a
reduced (23.3-57.0% and 37.2-38.1%) viral inhibitory effect in vero cells.
Furthermore, the caffeic acid plus Ribavirin (RBV) has greater antiviral activity
against CDV than the caffeic acid or RBV individually. In addition, the caffeic
acid reduced the total viral RNA synthesis by 59-86% at 24-72 h. Therefore, our
data provided the experimental evidence that the caffeic acid effectively
inhibited CDV infection in vero cells, which may potentially be used to treat
clinical disease associated with CDV infection.
PMID- 28687325
TI - Velocity perception in a moving observer.
AB - Previous research has shown that when a moving stimulus is presented to a moving
observer, the perceived speed of the stimulus is affected by vestibular self
motion signals (Hogendoorn, Verstraten, MacDougall, & Alais, 2017. Vision
Research 130, 22-30.). This interaction was interpreted as a weighted sum of
visual and vestibular motion signals. This interpretation also predicts effects
of vestibular self-motion signals on perceived speed. Here, we test this
prediction in two experiments. In Experiment 1, moving observers carried out a
visual speed discrimination task in order to establish points of subjective
equality (PSE) between stimuli presented in the same or opposite direction of
self-motion. We observed robust effects of self-motion on perceived speed, with
self-motion in the same direction as visual motion resulting in increases in
perceived speed and vice versa. These effects were well- described by a limited
width integration window. In Experiment 2, the same observers carried out another
speed discrimination task in order to establish discrimination thresholds.
According to the Weber-Fechner law, these thresholds are expected to increase or
decrease along with perceived speed. However, no effect of self-motion on
discrimination thresholds was observed. This pattern of results suggests a limit
on speed discrimination performance early in the visual system, with visuo
vestibular integration in later downstream areas. These results are consistent
with previous work on heading perception.
PMID- 28687326
TI - Cellular origin of intrinsic optical signals in the rabbit retina.
AB - Optical imaging of retinal intrinsic signals is a relatively new method that
provides spatiotemporal patterns of retinal activity through activity-dependent
changes in light reflectance of the retina. The exact physiological mechanisms at
the origin of retinal intrinsic signals are poorly understood and there are
significant inter-species differences in their characteristics and cellular
origins. In this study, we re-examined this issue through pharmacological
dissection of retinal intrinsic signals in the rabbit with simultaneous ERG
recordings. Retinal intrinsic signals faithfully reflected retinal activity as
their amplitude was strongly associated with stimulation intensity (r2=0.85).
Further, a strong linear relation was found using linear regression (r2=0.98)
between retinal intrinsic signal amplitude and the ERG b wave, which suggests
common cellular origins. Intravitreal injections of pharmacological agents were
performed to isolate the activity of the retina's major cell types. Retinal
intrinsic signals were abolished when the photoreceptors' activity was isolated
with aspartate, indicative that they are not at the origin of this signal. A
small but significant decrease in intrinsic response (20%) was observed when
ganglion and amacrine cells' activity was inhibited by TTX injections. The
remaining intrinsic responses were abolished in a dose-dependent manner through
the inhibition of ON-bipolar cells by APB. Our results indicate that, in rabbits,
retinal intrinsic signals reflect stimulation intensity and originate from the
inner retina with a major contribution of bipolar cells and a minor one from
ganglion or amacrine cells.
PMID- 28687327
TI - Masking of random-walk motion by flicker, and its role in the allocation of
motion in the on-line jitter illusion.
AB - Typically, perceptual stabilization mechanisms make us unaware of the retinal
image motion produced by the small, involuntary eye movements our eyes constantly
make during fixation. The breakdown of perceptual stability is demonstrated by
the on-line jitter illusion, in which a circular static pattern appears to jitter
coherently when surrounded by a flickering annular pattern. Although both regions
of the stimulus are subject to retinal motion from eye movements, the visual
system attributes this motion to the central static region in the form of visual
jitter, while the surrounding flickering region remains perceptually stable. We
investigated factors influencing this allocation of motion and reference frame in
the on-line jitter illusion. The flickering of the surround was found to impair
the detection of simultaneous random-walk motion in this area, giving a detection
reliability of around 80% for motion approximating that from fixational eye
movements. Changes to spatial texture and location of flicker (centre vs.
surrounding annulus) had little effect on the final percept. However, use of a
nonconcentric stimulus resulted in a marked reduction in apparent jitter in all
subjects. Our results suggest for the on-line jitter illusion, allocation of
motion and reference frame is influenced by the general principle that, if one
region surrounds another, the surrounding region tends to be allocated as the
frame of reference. When this factor is controlled for, spatial textures,
location of flicker, and the masking of motion by flicker have a smaller but
measurable influence on the final percept.
PMID- 28687328
TI - Representing dynamic stimulus information during occlusion.
AB - Human observers maintain a representation of the visual features of objects when
they become occluded. This representation facilitates the interpretation of
occluded events and allows us to quickly identify objects upon reappearing. Here
we investigated whether visual features that change over time are also
represented during occlusion. To answer this question we used an illusion from
the time perception domain in which the perceived duration of an event increases
as its temporal frequency content increases. In the first experiment we
demonstrate temporal frequency induced modulation of duration both when the
object remains visible as well as when it becomes temporarily occluded.
Additionally, we demonstrate that time dilation for temporarily occluded objects
cannot be explained by modulations of duration as a result of pre- and post
occlusion presentation of the object. In a second experiment, we corroborate this
finding by demonstrating that modulation of the perceived duration of occluded
events depends on the expected temporal frequency content of the object during
occlusion. Together these results demonstrate that the dynamic properties of an
object are represented during occlusion. We conclude that the representations of
occluded objects contain a wide range of features derived from the period when
the object was still visible, including information about both the static and
dynamic properties of the object.
PMID- 28687329
TI - 3D faces are recognized more accurately and faster than 2D faces, but with
similar inversion effects.
AB - Recognition of faces typically occurs via holistic processing where individual
features are combined to provide an overall facial representation. However, when
faces are inverted, there is greater reliance on featural processing where faces
are recognized based on their individual features. These findings are based on a
substantial number of studies using 2-dimensional (2D) faces and it is unknown
whether these results can be extended to 3-dimensional (3D) faces, which have
more depth information that is absent in the typical 2D stimuli used in face
recognition literature. The current study used the face inversion paradigm as a
means to investigate how holistic and featural processing are differentially
influenced by 2D and 3D faces. Twenty-five participants completed a delayed face
matching task consisting of upright and inverted faces that were presented as
both 2D and 3D stereoscopic images. Recognition accuracy was significantly higher
for 3D upright faces compared to 2D upright faces, providing support that the
enriched visual information in 3D stereoscopic images facilitates holistic
processing that is essential for the recognition of upright faces. Typical face
inversion effects were also obtained, regardless of whether the faces were
presented in 2D or 3D. Moreover, recognition performances for 2D inverted and 3D
inverted faces did not differ. Taken together, these results demonstrated that 3D
stereoscopic effects influence face recognition during holistic processing but
not during featural processing. Our findings therefore provide a novel
perspective that furthers our understanding of face recognition mechanisms,
shedding light on how the integration of stereoscopic information in 3D faces
influences face recognition processes.
PMID- 28687330
TI - Identification of PEG-induced water stress responsive transcripts using co
expression network in Eucalyptus grandis.
AB - Ecophysiological studies in Eucalyptus have shown that water is the principal
factor limiting stem growth. Effect of water deficit conditions on physiological
and biochemical parameters has been extensively reported in Eucalyptus. The
present study was conducted to identify major polyethylene glycol induced water
stress responsive transcripts in Eucalyptus grandis using gene co-expression
network. A customized array representing 3359 water stress responsive genes was
designed to document their expression in leaves of E. grandis cuttings subjected
to -0.225MPa of PEG treatment. The differentially expressed transcripts were
documented and significantly co-expressed transcripts were used for construction
of network. The co-expression network was constructed with 915 nodes and 3454
edges with degree ranging from 2 to 45. Ninety four GO categories and 117
functional pathways were identified in the network. MCODE analysis generated 27
modules and module 6 with 479 nodes and 1005 edges was identified as the
biologically relevant network. The major water responsive transcripts represented
in the module included dehydrin, osmotin, LEA protein, expansin,
arabinogalactans, heat shock proteins, major facilitator proteins, ARM repeat
proteins, raffinose synthase, tonoplast intrinsic protein and transcription
factors like DREB2A, ARF9, AGL24, UNE12, WLIM1 and MYB66, MYB70, MYB 55, MYB 16
and MYB 103. The coordinated analysis of gene expression patterns and
coexpression networks developed in this study identified an array of transcripts
that may regulate PEG induced water stress responses in E. grandis.
PMID- 28687331
TI - A global evolutionary and metabolic analysis of human obesity gene risk variants.
AB - It is generally accepted that the selection of gene variants during human
evolution optimized energy metabolism that now interacts with our obesogenic
environment to increase the prevalence of obesity. The purpose of this study was
to perform a global evolutionary and metabolic analysis of human obesity gene
risk variants (110 human obesity genes with 127 nearest gene risk variants)
identified using genome-wide association studies (GWAS) to enhance our knowledge
of early and late genotypes. As a result of determining the mean frequency of
these obesity gene risk variants in 13 available populations from around the
world our results provide evidence for the early selection of ancestral risk
variants (defined as selection before migration from Africa) and late selection
of derived risk variants (defined as selection after migration from Africa). Our
results also provide novel information for association of these obesity genes or
encoded proteins with diverse metabolic pathways and other human diseases. The
overall results indicate a significant differential evolutionary pattern for the
selection of obesity gene ancestral and derived risk variants proposed to
optimize energy metabolism in varying global environments and complex association
with metabolic pathways and other human diseases. These results are consistent
with obesity genes that encode proteins possessing a fundamental role in
maintaining energy metabolism and survival during the course of human evolution.
PMID- 28687333
TI - Predicting novel genes and pathways associated with osteosarcoma by using
bioinformatics analysis.
AB - This aim of this study was to explore novel biomarkers related to osteosarcoma.
The mRNA expression profile GSE41293 dataset was downloaded from the Gene
Expression Omnibus (GEO) database, which included seven osteosarcoma and six
control samples. After preprocessing, the FASTQ format reads of 13 samples were
mapped to the reference sequences to screen for unique mapping reads.
Differentially expressed genes (DEGs) were selected, which were then used for
pathway and protein-protein interaction (PPI) network analyses. Moreover, the
microarray data GSE63631 were downloaded from GEO database to verify our results.
The percentages of unique mapping reads for osteosarcomas and control samples
were both >85%. A total of 6157 DEGs were identified between the two groups. DEGs
that were upregulated were significantly enriched in 19 pathways, and those that
were downregulated were enriched in 14 pathways. In the PPI network, DEGs such as
SRC, ERBB2, and CAV3 in cluster 1 were enriched in the pathway responsible for
focal adhesions. The DEGs in cluster 2, such as CDK4 and CDK6, were enriched in
the cell cycle pathway. In GSE63631, DEGs were significantly enriched in focal
adhesion pathway, which was in accordance with the result in GSE41293. Thus, the
focal adhesion and cell cycle pathways may play important roles in osteosarcoma
progression, and SRC, ERBB2, CAV3, CDK4, and CDK6 may be used as critical
biomarkers of osteosarcoma.
PMID- 28687332
TI - Systemic analysis of different colorectal cancer cell lines and TCGA datasets
identified IGF-1R/EGFR-PPAR-CASPASE axis as important indicator for radiotherapy
sensitivity.
AB - Insulin-like growth factor 1 receptor (IGF-1R) is proved to contribute the
development of many types of cancers. But, little is known about its roles in
radio-resistance of colorectal cancer (CRC). Here, we demonstrated that low IGF
1R expression value was associated with the better radiotherapy sensitivity of
CRC. Besides, through Quantitative Real-time PCR (qRT-PCR), the elevated
expression value of epidermal growth factor receptor (EGFR) was observed in CRC
cell lines (HT29, RKO) with high radio-sensitivity compared with those with low
sensitivity (SW480, LOVO). The irradiation induced apoptosis rates of wild type
and EGFR agonist (EGF) or IGF-1R inhibitor (NVP-ADW742) treated HT29 and SW480
cells were quantified by flow cytometry. As a result, the apoptosis rate of EGF
and NVP-ADW742 treated HT29 cells was significantly higher than that of those
wild type ones, which indicated that high EGFR and low IGF-1R expression level in
CRC was associated with the high sensitivity to radiotherapy. We next conducted
systemic bioinformatics analysis of genome-wide expression profiles of CRC
samples from the Cancer Genome Atlas (TCGA). Differential expression analysis
between IGF-1R and EGFR abnormal CRC samples, i.e. CRC samples with higher IGF-1R
and lower EGFR expression levels based on their median expression values, and the
rest of CRC samples identified potential genes contribute to radiotherapy
sensitivity. Functional enrichment of analysis of those differential expression
genes (DEGs) in the Database for Annotation, Visualization and Integrated
Discovery (DAVID) indicated PPAR signaling pathway as an important pathway for
the radio-resistance of CRC. Our study identified the potential biomarkers for
the rational selection of radiotherapy for CRC patients.
PMID- 28687334
TI - A cysteine protease (cathepsin Z) from disk abalone, Haliotis discus discus:
Genomic characterization and transcriptional profiling during bacterial
infections.
AB - Cathepsin Z (CTSZ) is lysosomal cysteine protease of the papain superfamily. It
participates in the host immune defense via phagocytosis, signal transduction,
cell-cell communication, proliferation, and migration of immune cells such as
monocytes, macrophages, and dendritic cells. Hence, CTSZ is also acknowledged as
an acute-phase protein in host immunity. In this study, we sought to identify the
CTSZ homolog from disk abalone (AbCTSZ) and characterize it at the molecular,
genomic, and transcriptional levels. AbCTSZ encodes a protein with 318 amino
acids and a molecular mass of 36kDa. The structure of AbCTSZ reveals amino acid
sequences that are characteristic of the signal sequence, pro-peptide, peptidase
C1 papain family cysteine protease domain, mini-loop, HIP motif, N-linked
glycosylation sites, active sites, and conserved Cys residues. A pairwise
comparison revealed that AbCTSZ shared the highest amino acid homology with its
molluscan counterpart from Crassostrea gigas. A multiple alignment analysis
revealed the conservation of functionally crucial elements of AbCTSZ, and a
phylogenetic study further confirmed a proximal evolutionary relationship with
its invertebrate counterparts. Further, an analysis of AbCTSZ genomic structure
revealed seven exons separated by six introns, which differs from that of its
vertebrate counterparts. Quantitative real time PCR (qPCR) detected the
transcripts of AbCTSZ in early developmental stages and in eight different
tissues. Higher levels of AbCTSZ transcripts were found in trochophore, gill, and
hemocytes, highlighting its importance in the early development and immunity of
disk abalone. In addition, we found that viable bacteria (Vibrio parahaemolyticus
and Listeria monocytogenes) and bacterial lipopolysaccharides significantly
modulated AbCTSZ transcription. Collectively, these lines of evidences suggest
that AbCTSZ plays an indispensable role in the innate immunity of disk abalone.
PMID- 28687335
TI - A genome-wide transcriptomic analysis of articular cartilage during normal
maturation in pigs.
AB - OBJECTIVE: The articular cartilage undergoes dramatic changes in structure and
composition during post-natal maturation, but the associated transcriptional
changes are not well characterized. Compared to a mature stage, the immature
articular cartilage shows developmental features such as increased thickness,
presence of blood vessels, and the presence of a deep layer of growth cartilage
which undergoes endochondral ossification. These features decrease during normal
development. Following maturation, the articular cartilage is known to undergo
few minor modifications. Since mature articular cartilage has poor regenerative
and repair capacity compared to the immature articular cartilage, a better
understanding of the molecular changes during the normal postnatal articular
cartilage development might reveal insights on the molecular adaptation. It may
also provide new therapeutic strategies. The purpose of this study was to
determine the differential expression of genes in the femoral head articular
cartilage of 6-weeks old and 6-months old pigs using a genome-wide transcriptomic
analysis. METHODS: The articular cartilage of the femoral head of 6-weeks and 6
months old normal pigs was assessed for thickness and vascularity (number of
vascular canals) using Safranin O/Fast Green staining of paraffin sections (n=4
pigs/age group). The measurements were determined using Image J software. RNA was
isolated from the femoral head articular cartilage from 6-weeks and 6-months old
pigs (n=8 pigs/age group). A microarray analysis was performed using an
Affymetrix Porcine GeneChip Array. A gene enrichment analysis and a functional
clustering analysis were performed by DAVID and STRING software, respectively.
The differential expression of selected genes was confirmed by a quantitative
RTPCR analysis. RESULTS: The femoral head articular cartilage showed a
significant decrease in thickness and number of vascular canals in 6-months old
compared to 6-weeks old pigs. A microarray analysis revealed a differential gene
expression of 576 genes, with 206 genes that were significantly upregulated and
370 genes that were significantly downregulated (>2-fold change, p<0.05) at 6
months compared to 6-weeks of age. Among the upregulated genes, DAVID analysis
revealed that a significant number of genes represented the biological processes
of responses to external stimuli, and wounding and inflammation at 6-months of
age. These processes involved genes representing secretory and signaling proteins
such as MMP-1, MMP-3, IL-8 and STAT3 suggesting increased inflammatory activity.
In addition, an assessment of the downregulated genes indicated a decrease in the
expression of genes representing the biological processes of developmental
processes (e.g. BMPR1A, BMPR2, ACVR2, periostin, SFRP2, COL5A3) and regulation of
blood vessel size (e.g. alpha adrenergic receptor 1B, alpha-SMA) at 6-months of
age. A real-time qRTPCR analysis of selected upregulated genes, fibronectin, MMP
3, IL-8 and downregulated genes, BMPR2, PECAM, CCL2, TLR4 confirmed the
differential gene expression in the microarray analysis. CONCLUSION: During the
process of articular cartilage maturation from 6-weeks to 6-months of age in
normal pigs, genes associated with inflammatory responses to injury were
upregulated and genes involved in the development and vascular responses were
downregulated. These findings suggest that during articular cartilage maturation,
the transcriptional changes might increase the susceptibility of cartilage to
inflammatory damage and decrease the regenerative capacity.
PMID- 28687336
TI - Polymorphisms of CYP2C8, CYP2C9 and CYP2C19 and risk of coronary heart disease in
Russian population.
AB - Epoxyeicosatrienoic acids (EETs) are important vasoactive products of arachidonic
acid metabolism with a wide range of biological actions in the cardiovascular
system. The present study investigated whether single nucleotide polymorphisms
(SNP) of genes coding cytochrome P450 2C subfamily, enzymes involved in
biosynthesis of EETs, are associated with the risk of coronary heart disease
(CHD). A total of 1255 unrelated Russian subjects comprising 561 patients with
angiographically diagnosed CHD and 694 age- and sex-matched healthy subjects were
included in the study. DNA samples from all study participants were genotyped for
six common SNPs rs7909236, rs1934953 of CYP2C8, rs9332242, rs4918758 and
rs61886769 of CYP2C9 and rs4244285 of CYP2C19 using by the Mass-ARRAY 4 system.
SNP rs4918758 of CYP2C9 was associated with decreased risk of CHD (codominant
model) at a borderline significance with odds ratio adjusted for sex and age 0.61
(95% CI: 0.41-0.92, P=0.038, Q=0.20). SNP rs9332242 of CYP2C9 showed a trend
towards association with increased CHD risk in cigarette smokers (P=0.049,
Q=0.29). Log-likelihood ratio test (LRT) pointed out epistatic interactions
between rs9332242 and rs61886769 of CYP2C9 (codominant model, Pinteraction=0.02),
however, this P-value did not survive after correction for multiple tests.
Bioinformatic analysis revealed a regulatory potential for a majority of the
investigated SNPs. Our preliminary results demonstrate that polymorphisms of
genes encoding CYP2C subfamily represent potential genetic markers of CHD
susceptibility. Further studies are required to substantiate the contribution of
these genes to the disease risk.
PMID- 28687337
TI - A translational synthetic biology platform for rapid access to gram-scale
quantities of novel drug-like molecules.
AB - Plants are an excellent source of drug leads. However availability is limited by
access to source species, low abundance and recalcitrance to chemical synthesis.
Although plant genomics is yielding a wealth of genes for natural product
biosynthesis, the translation of this genetic information into small molecules
for evaluation as drug leads represents a major bottleneck. For example, the
yeast platform for artemisinic acid production is estimated to have taken >150
person years to develop. Here we demonstrate the power of plant transient
transfection technology for rapid, scalable biosynthesis and isolation of
triterpenes, one of the largest and most structurally diverse families of plant
natural products. Using pathway engineering and improved agro-infiltration
methodology we are able to generate gram-scale quantities of purified triterpene
in just a few weeks. In contrast to heterologous expression in microbes, this
system does not depend on re-engineering of the host. We next exploit agro
infection for quick and easy combinatorial biosynthesis without the need for
generation of multi-gene constructs, so affording an easy entree to suites of
molecules, some new-to-nature, that are recalcitrant to chemical synthesis. We
use this platform to purify a suite of bespoke triterpene analogs and demonstrate
differences in anti-proliferative and anti-inflammatory activity in bioassays,
providing proof of concept of this system for accessing and evaluating
medicinally important bioactives. Together with new genome mining algorithms for
plant pathway discovery and advances in plant synthetic biology, this advance
provides new routes to synthesize and access previously inaccessible natural
products and analogs and has the potential to reinvigorate drug discovery
pipelines.
PMID- 28687339
TI - Inflammation and myointimal hyperplasia. Correlation with hemodynamic forces.
AB - OBJECTIVES: The aim of our study was to correlate flow dynamics and the release
of inflammatory cytokines Interleukin 1, 2, 6, TNF (Tumour Necrosis Factor) alfa,
both in vitro and in vivo. MATERIALS AND METHODS: Endothelial cells were exposed
to laminar flow (6dyne/cm2) in an in vitro circulatory system and the release of
Interleukin 1, 2, 6 and TNF alfa was quantified by ELISA. Interleukin 1, 2, 6 and
TNF alfa release was also assessed in vein grafts implanted in the arterial
circulation of Lewis rats. Arterial vein grafts were explanted at different time
intervals from 3days to 12weeks after surgery. Vein grafts implanted in the
arterial circulation for 4weeks, were re implanted in the venous circulation of
syngenic Lewis rats, and the release of Interleukin 1, 2, 6 and TNF alfa, was
assessed in an organ culture. Six vein grafts (4 occluded, 2 patent) implanted in
humans as femorodistal bypass were examined for the presence of myointimal
hyperplasia and perigraft inflammatory cells. RESULTS: In vitro, endothelial
cells exposed to laminar flow released an increased amount of Interleukin 1, 2, 6
and TNF alfa in comparison to endothelial cells not exposed to flow. In
experimental vein grafts implanted in the arterial circulation there was an
increased release of inflammatory cytokines associated to inflammatory changes in
the adventitia. Once the vein grafts were re implanted in the venous circulation,
the release of these cytokines diminished, while the inflammatory changes in the
adventitia regressed. CONCLUSIONS: Increased shear stress induces release of
cytokines and inflammatory changes in the adventitia. These inflammatory changes
can contribute to plaque progression and to un stable plaque. These findings
support the use of anti-inflammatory therapy in patients prone to develop
atherosclerosis and in those who had arterial reconstructive surgery.
PMID- 28687338
TI - Replicative DNA polymerase defects in human cancers: Consequences, mechanisms,
and implications for therapy.
AB - The fidelity of DNA replication relies on three error avoidance mechanisms acting
in series: nucleotide selectivity of replicative DNA polymerases, exonucleolytic
proofreading, and post-replicative DNA mismatch repair (MMR). MMR defects are
well known to be associated with increased cancer incidence. Due to advances in
DNA sequencing technologies, the past several years have witnessed a long
predicted discovery of replicative DNA polymerase defects in sporadic and
hereditary human cancers. The polymerase mutations preferentially affect
conserved amino acid residues in the exonuclease domain and occur in tumors with
an extremely high mutation load. Thus, a concept has formed that defective
proofreading of replication errors triggers the development of these tumors.
Recent studies of the most common DNA polymerase variants, however, suggested
that their pathogenicity may be determined by functional alterations other than
loss of proofreading. In this review, we summarize our current understanding of
the consequences of DNA polymerase mutations in cancers and the mechanisms of
their mutator effects. We also discuss likely explanations for a high recurrence
of some but not other polymerase variants and new ideas for therapeutic
interventions emerging from the mechanistic studies.
PMID- 28687340
TI - Brain renin-angiotensin system in the pathophysiology of cardiovascular diseases.
AB - Cardiovascular diseases (CVD) are among the main causes of death globally and in
this context hypertension represents one of the key risk factors for developing a
CVD. It is well established that the peripheral renin-angiotensin system (RAS)
plays an important role in regulating blood pressure (BP). All components of the
classic RAS can also be found in the brain but, in contrast to the peripheral
RAS, how the endogenous RAS is involved in modulating cardiovascular effects in
the brain is not fully understood yet. It is a complex system that may work
differently in diverse areas of the brain and is linked to the peripheral system
by the circumventricular organs (CVO), which do not have a blood brain barrier
(BBB). In this review, we focus on the brain angiotensin peptides, their
interactions with each other, and the consequences in the central nervous system
(CNS) concerning cardiovascular control. Additionally, we present potential drug
targets in the brain RAS for the treatment of hypertension.
PMID- 28687341
TI - Carbenoxolone prevents chemical eye ischemia-reperfusion-induced cell death via
11beta-hydroxysteroid dehydrogenase type 1 inhibition.
AB - Glaucoma is one of the leading causes of preventable blindness diseases,
affecting more than 2 million people in the United States. Recently, 11beta
hydroxysteroid dehydrogenase type 1 (11beta-HSD1) inhibitors were found to exert
preventive effects against glaucoma. Therefore, we investigated whether
carbenoxolone (CBX), an 11beta-HSD1 inhibitor, prevents chemical ischemia
reperfusion-induced cell death in human trabecular meshwork (HTM) cells. The
present study demonstrated that CBX inhibited cell death caused by iodoacetic
acid (IAA)-induced ischemia-reperfusion, and its effect was associated with the
inhibition of 11beta-HSD1 expression and activity. Furthermore, CBX reversed the
IAA-induced structural damage on filamentous actin in HTM cells. In IAA-treated
cells, the levels of 11beta-HSD1 and the apoptosis-related factors Bax and FASL
were increased throughout the reperfusion period, and CBX was able to attenuate
the expression of 11beta-HSD1 and the apoptosis-related factors. CBX also
effectively suppressed IAA-induced intracellular ROS formation and cytochrome c
release, which are involved in the mitochondrial apoptosis pathway. In addition,
IAA-induced chemical ischemia-reperfusion stimulated TNF-alpha expression and NF
kappaB p65 phosphorylation, and these effects were attenuated by CBX. 11beta-HSD1
RNAi also suppressed IAA-induced cell apoptosis via reduction of oxidative stress
and inhibition of the pro-inflammatory pathway. Taken together, the present study
demonstrated that the inhibition of 11beta-HSD1 protected the TM against chemical
ischemia-reperfusion injury, suggesting that the use of 11beta-HSD1 inhibitors
could be a useful strategy for glaucoma therapy.
PMID- 28687342
TI - Comparison of ultrasonography and radiography in diagnosis of rib fractures.
AB - PURPOSE: Rib fractures are the most common skeletal thoracic injuries resulting
from blunt chest trauma. Half of the rib fractures are not detected upon a
precise physical evaluation and radiographs. Recently ultrasonography (USG) has
been investigated to detect rib fractures. But based on literature the usefulness
of USG varies widely. This study was conducted to investigate the role of USG in
the detection of possible rib fractures in comparison with radiography. METHODS:
In this cross-sectional study, consecutive patients with minor blunt chest trauma
and suspected rib fractures presenting in Imam Reza Hospital located in Mashhad
Iran, between April 2013 and October 2013 were assessed by USG and radiography.
The radiography was performed in a posteroanterior (PA) chest projection and
oblique rib view centered over the area of trauma. The time duration spent in
taking USG and radiography were recorded. The prevalence and location of
fractures revealed by USG and radiography were compared. RESULTS: Sixty-one
suspected patients were assessed. The male to female ratio was 2.4:1 (43 men and
18 women) with a mean +/- SD age of (44.3 +/- 19.7) years. There were totally 59
rib fractures in 38 (62.3%) patients based on radiography and USG, while 23
(37.7%) patients had no diagnostic evidence of rib lesions. USG revealed 58 rib
fractures in 33 (54.1%) of 61 suspected patients and radiographs revealed 32 rib
fractures in 20 (32.8%) of 61 patients. A total of 58 (98.3%) rib fractures were
detected by USG, whereas oblique rib view and PA chest radiography showed 27
(45.8%) and 24 (40.7%) rib fractures, respectively. The average duration of USG
was (12 +/- 3) min (range 7-17 min), whereas the duration of radiography was (27
+/- 6) min (range 15-37 min). The kappa coefficient showed a low level of
agreement between both USG and PA chest radiography (kappa coefficient = 0.28),
and between USG and oblique rib view (kappa coefficient = 0.32). CONCLUSION: USG
discloses more fractures than radiography in most patients presenting with
suspected rib fractures. Moreover USG requires significantly less time than
radiography.
PMID- 28687343
TI - The Montreux definition of neonatal ARDS: biological and clinical background
behind the description of a new entity.
AB - Acute respiratory distress syndrome (ARDS) is undefined in neonates, despite the
long-standing existing formal recognition of ARDS syndrome in later life. We
describe the Neonatal ARDS Project: an international, collaborative, multicentre,
and multidisciplinary project which aimed to produce an ARDS consensus definition
for neonates that is applicable from the perinatal period. The definition was
created through discussions between five expert members of the European Society
for Paediatric and Neonatal Intensive Care; four experts of the European Society
for Paediatric Research; two independent experts from the USA and two from
Australia. This Position Paper provides the first consensus definition for
neonatal ARDS (called the Montreux definition). We also provide expert consensus
that mechanisms causing ARDS in adults and older children-namely complex
surfactant dysfunction, lung tissue inflammation, loss of lung volume, increased
shunt, and diffuse alveolar damage-are also present in several critical neonatal
respiratory disorders.
PMID- 28687344
TI - Anterior cervical discectomy and fusion versus posterior laminoplasty for
multilevel cervical myelopathy: A meta-analysis.
AB - OBJECT: Anterior cervical discectomy with fusion (ACDF) and laminoplasty (LAMP)
are used for the treatment of multilevel cervical myelopathy. Despite their
widespread applications certain differences are noted between the ACDF and LAMP
procedures. A meta-analysis was conducted in order to compare the clinical
outcomes, complications, and surgical trauma between ACDF and LAMP for the
treatment of multilevel cervical myelopathy. METHODS: Medline, EMBASE, Google
Scholar, and Cochrane databases were used for the search of relevant studies
until September 2016. The studies aimed to compare the ACDF and LAMP procedures
for the treatment of multilevel cervical myelopathy. Title and abstract screening
was carried out concomitantly, whereas full text screening was carried out
independently. A random effect model was used for heterogeneous data. The data
that did not follow heterogeneous pattern were pooled by a fixed effect model in
order to examine the mean difference (MD) for continuous outcomes and the odds
ratio (OR) for dichotomous outcomes, respectively. RESULTS: A total of 6 articles
out of 1351 citations (379 participants) were eligible. Significant differences
were noted between the two groups in the cobb angle of C2-C7 (MD = 4.00, 95%, CI
= 0.83 to 7.17; p = 0.01) and with regard to the incidence of associated
complications (OR = 3.61, 95%, CI = 1.72 to 7.59; p = 0.0007). However, no
apparent differences were noted in the variables blood loss (MD = -24.16, 95% CI
= -174.47 to 126.15; p = 0.75), operation time ((MD = 32.81, 95% CI = -26.76 to
92.38; p = 0.28), recovery rate of JOA score (MD = 4.00, 95%, CI = 0.83 to 7.17;
p = 0.01) and incidence of associated complications (OR = 3.61, 95%, CI = 1.72 to
7.59). CONCLUSIONS: The present meta-analysis demonstrates that the rate of
complications is lower in the laminoplasty. However, the cobb angle of C2-C7 was
decreased in the ACDF group at the final follow-up period compared with the
baseline. The outcomes of the variables blood loss, operation time, range of
motion and recovery rate of JOA score, were similar in the two groups.
PMID- 28687345
TI - Molecular diversity, geographic distribution and host range of monocot-infecting
mastreviruses in Africa and surrounding islands.
AB - Maize streak virus (MSV), an important pathogen of maize in Africa, is the most
extensively studied member of the Mastrevirus genus in the family Geminiviridae.
Comparatively little is known about other monocot-infecting African
mastreviruses, most of which infect uncultivated grasses. Here we determine the
complete sequences of 134 full African mastrevirus genomes from predominantly
uncultivated Poaceae species. Based on established taxonomic guidelines for the
genus Mastrevirus, these genomes could be classified as belonging to the species
Maize streak virus, Eragrostis minor streak virus, Maize streak Reunion virus,
Panicum streak virus, Sugarcane streak Reunion virus and Sugarcane streak virus.
Together with all other publicly available African monocot-infecting
mastreviruses, the 134 new isolates extend the known geographical distributions
of many of these species, including MSV which we found infecting Digitaria sp. on
the island of Grand Canaria: the first definitive discovery of any African
monocot-infecting mastreviruses north-west of the Saharan desert. These new
isolates also extend the known host ranges of both African mastrevirus species
and the strains within these. Most notable was the discovery of MSV-C isolates
infecting maize which suggests that this MSV strain, which had previously only
ever been found infecting uncultivated species, may be in the process of becoming
adapted to this important staple crop.
PMID- 28687346
TI - Solid state characterisation and taste masking efficiency evaluation of polymer
based extrudates of isoniazid for paediatric administration.
AB - Hot melt extrusion has gained considerable attention as a novel technique for
taste masking of bitter APIs. The aim of this study was to investigate whether
hot melt extrusion could be used to develop taste masked formulations of
isoniazid and also to evaluate and correlate different taste assessment methods
Two polymers with different physico-chemical properties, Soluplus and Eudragit E
PO were chosen as carriers for the drug. Eudragit E-PO has already been widely
used for taste masking due to its selective release properties, while Soluplus
has not been studied in this regard but provides a useful comparator of a polymer
that should release the drug reasonably efficiently. Polymeric formulations of
isoniazid were produced with drug loadings of 20% and 30% w/w. The solid state
characteristics of the formulations were assessed by differential scanning
calorimetry and powder X-ray diffraction. The taste of isoniazid was assessed
using the rodent Brief Access Taste Aversion (BATA) model, while formulations
were assessed using the electronic tongue and dissolution under simulated oral
conditions. Investigation into the drug loading effect with these two polymers
showed that all Soluplus based extrudates with drug loading up to 30% w/w were
fully amorphous while Eudragit E-PO based extrudates contained crystalline drug
as demonstrated by both DSC and PXRD, dependent on loading. BATA testing of
isoniazid gave an IC50 value, i.e. the dose of drug which inhibits 50% of licks,
of 11.1mg/mL. Taste assessment of the formulations using both simulated oral drug
release and the electronic tongue demonstrated that Eudragit E-PO based
formulations had a better taste masking efficiency than Soluplus. This is due to
the fact that significantly less isoniazid is released from the Eudragit E-PO
based formulations under oral conditions.
PMID- 28687347
TI - HESTAT: Study protocol for a phase II/III, randomized, placebo-controlled, single
blind study to evaluate the new hemostatic agent TT-173 in total knee
arthroplasty.
AB - BACKGROUND: Several hemostatic treatments intended to reduce the bleeding
associated to total knee arthroplasty have been investigated with varying degrees
of success. TT-173 is a new topical agent based on recombinant tissue factor that
activates the extrinsic pathway of coagulation. This trial aim is to evaluate the
efficacy and safety of TT-173 in total knee arthroplasty. METHODS/DESIGN: This is
a phase II/III, sequential, simple blind, randomized, multicenter, placebo
controlled and parallel clinical trial that will recruit 189 evaluable patients.
Those randomized to treatment group will receive 2mg of TT-173 over the surgical
surfaces of the knee. Control patients will receive physiologic saline. The
follow up will consist in 6 visits during a period of 35 (+/-7) days. Primary
endpoints will be the total blood loss and the incidence and severity of adverse
events. Secondary and exploratory endpoints will include drainage production,
decrease in hemoglobin level, transfusion ratio, analytical alterations, pain
intensity, motion range, immunogenicity of TT-173 and the occurrence of systemic
absorption. At the end of phase II, results will be evaluated by an independent
committee that will recommend the continuation or the discontinuation of the
trial. DISCUSSION: The design proposed maximizes the safety of the participants,
avoids the risk of bias derived from the limitations of masking and enable the
eventual discontinuation of the trial if this is recommended by the Interim
Analysis Committee. If TT-173 proves its efficacy and safety in this indication,
it would become a useful tool to improve the bleeding control in total knee
arthroplasty. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02687399.
Registered the 9th of February 2016.
PMID- 28687350
TI - Clinical response to long-term tenofovir monotherapy in Korean chronic hepatitis
B patients.
AB - BACKGROUND: Tenofovir disoproxil fumarate (TDF) is a potent nucleotide analogue
recommended as first-line monotherapy for chronic hepatitis B (CHB). We
investigated the clinical response to TDF monotherapy in Korean CHB patients.
METHODS: A total of 90 CHB patients [55 hepatitis B e antigen (HBeAg)-positive
and 35 HBeAg-negative] who received TDF monotherapy for >2year, were enrolled.
Quantitative hepatitis B surface antigen (qHBsAg) levels, serum alanine
aminotransferase (ALT), HBeAg, anti-HBe and HBV DNA levels were measured during
treatment. Virologic response (VR) was defined as undetectable HBV DNA level.
RESULTS: The cumulative incidences of complete virologic response (CVR) were
75.6% and 89.9% at months 12 and 24, respectively. The cumulative CVR rates were
significantly higher in HBeAg-negative than HBeAg-positive group (P<0.001). HBeAg
loss/seroconversion was observed in 21 (38.2%) out of 55 HBeAg-positive patients.
One HBeAg-positive and 1 HBeAg-negative patients (2.2%) achieved HBsAg loss at
months 6 and 8 of TDF therapy, respectively. Baseline HBV DNA level and qHBsAg
were significant predictive factors for a CVR (P=0.001 and P<0.001,
respectively). CONCLUSIONS: Virologic, serologic, biochemical responses were
achieved in both HBeAg-positive and HBeAg-negative patients under 24-month TDF
therapy. Monitoring using baseline HBV DNA and qHBsAg levels would be helpful to
predict CVR.
PMID- 28687348
TI - Design and approach of the Living Organ Video Educated Donors (LOVED) program to
promote living kidney donation in African Americans.
AB - PURPOSE: To describe the rationale, methodology, design, and interventional
approach of a mobile health education program designed for African Americans with
end stage renal disease (ESRD) to increase knowledge and self-efficacy to
approach others about their need for a living donor kidney transplant (LDKT).
METHODS: The Living Organ Video Educated Donors (LOVED) program is a theory
guided iterative designed, mixed methods study incorporating three phases: 1) a
formative evaluation using focus groups to develop program content and approach;
2) a 2-month proof of concept trial (n=27) to primarily investigate
acceptability, tolerability and investigate increases of LDKT knowledge and self
efficacy; and 3) a 6-month, 2-arm, 60-person feasibility randomized control trial
(RCT) to primarily investigate increases in LDKT knowledge and self-efficacy, and
secondarily, to increase the number of living donor inquiries, medical
evaluations, and LDKTs. The 8-week LOVED program includes an interactive web
based app delivered on 10" tablet computer incorporating weekly interactive video
education modules, weekly group video chat sessions with an African American
navigator who has had LDKT and other group interactions for support and improve
strategies to promote their need for a kidney. RESULTS: Phase 1 and 2 have been
completed and the program is currently enrolling for the feasibility RCT. Phase 2
experienced 100% retention rates with 91% adherence completing the video modules
and 88% minimum adherence to the video chat sessions. CONCLUSIONS: We are in the
early stages of an RCT to evaluate the LOVED program; to date, we have found high
tolerability reported from Phase 2.
PMID- 28687349
TI - Program for lung cancer screening and tobacco cessation: Study protocol of a
sequential, multiple assignment, randomized trial.
PMID- 28687351
TI - Prevalence of anti-NT5C1A antibodies in Japanese patients with autoimmune
rheumatic diseases in comparison with other patient cohorts.
AB - BACKGROUND: Sporadic inclusion body myositis (sIBM) is usually classified as an
idiopathic inflammatory myopathies. Although the diagnosis of sIBM is sometimes
challenging, recent studies have shown that the autoantibodies against cytosolic
5'-nucleotidase 1A (NT5C1A) are the possible diagnostic biomarker for sIBM. Few
reports have shown the frequencies of anti-NT5C1A antibodies in systemic
autoimmune rheumatic diseases (SARDs) using large cohorts of SARDs. METHODS:
Serum samples obtained from 314 patients including dermatomyositis (DM) (n=144),
systemic lupus erythematosus (SLE) (n=50), systemic sclerosis (SSc) (n=50),
Sjogren's syndrome (SS) (n=50), polymyositis (PM) (n=10) and mixed connective
tissue disease (n=10), and healthy controls (n=42) in addition to 10 patients
with typical sIBM were analysed for the presence of autoantibodies using full
length recombinant NT5C1A ELISA. RESULTS: Japanese patients with DM (11%), PM
(10%), SLE (6%), SSc (8%) or SS (4%) had anti-NT5C1A antibodies at lower
frequencies than patients with sIBM. Interestingly, 4 of 17 DM/PM patients with
anti-NT5C1A antibodies were found to have no other myositis-specific/associated
autoantibodies. CONCLUSIONS: There is a wide heterogeneity of anti-NT5C1A
antibody immunoreactivity. Some populations of SARDs are positive for anti-NT5C1A
are also positive for anti-NT5C1A. However, the anti-NT5C1A frequencies in the
patients with SARDs are low also in Japanese.
PMID- 28687353
TI - p27Kip1 and human cancers: A reappraisal of a still enigmatic protein.
AB - p27Kip1 is a cell cycle regulator firstly identified as a cyclin-dependent kinase
inhibitor. For a long time, its function has been associated to cell cycle
progression inhibition at G1/S boundary in response to antiproliferative stimuli.
The picture resulted complicated by the discovery that p27Kip1 is an
intrinsically unstructured protein, with numerous CDK-dependent and -independent
functions and involvement in many cellular processes, such as cytoskeleton
dynamics and cell motility control, apoptosis and autophagy activation. Depending
on the cell context, these activities might turn to be oncogenic and stimulate
cancer progression and metastatization. Nevertheless, p27Kip1 role in cancer
biology suppression was underscored by myriad data reporting its down-regulation
and/or cytoplasmic relocalization in different tumors, while usually no genetic
alterations were found in human cancers, making the protein a non-canonical
oncosuppressor. Recently, mostly due to advances in genomic analyses, CDKN1B,
p27Kip1 encoding gene, has been found mutated in several cancers, thus leading to
a profound reappraisal of CDKN1B role in tumorigenesis. This review summarizes
the main p27Kip1 features, with major emphasis to its role in cancer biology and
to the importance of CDKN1B mutations in tumor development.
PMID- 28687352
TI - Gemcitabine enhances the transport of nanovector-albumin-bound paclitaxel in
gemcitabine-resistant pancreatic ductal adenocarcinoma.
AB - The mechanism for improved therapeutic efficacy of the combination therapy with
nanoparticle albumin-bound paclitaxel (nAb-PTX) and gemcitabine (gem) for
pancreatic ductal adenocarcinoma (PDAC) has been ascribed to enhanced gem
transport by nAb-PTX. Here, we used an orthotopic mouse model of gem-resistant
human PDAC in which increasing gem transport would not improve the efficacy, thus
revealing the importance of nAb-PTX transport. We aimed to evaluate therapeutic
outcomes and transport of nAb-PTX to PDAC as a result of (1) encapsulating nAb
PTX in multistage nanovectors (MSV); (2) effect of gem on caveolin-1 expression.
Treatment with MSV/nAb-PTX + gem was highly efficient in prolonging animal
survival in comparison to other therapeutic regimens. MSV/nAb-PTX + gem also
caused a substantial increase in tumor PTX accumulation, significantly reduced
tumor growth and tumor cell proliferation, and increased apoptosis. Moreover, gem
enhanced caveolin-1 expression in vitro and in vivo, thereby improving transport
of nAb-PTX to PDAC. This data was confirmed by analysis of PDACs from patients
who received gem-based neo-adjuvant chemotherapy. In conclusion, we found that
nAb-PTX treatment of gem-resistant PDAC can be enhanced by (1) gem through up
regulation of caveolin-1 and (2) MSV through increasing accumulation of nAb-PTX
in the tumor.
PMID- 28687354
TI - Aspirin disrupts the mTOR-Raptor complex and potentiates the anti-cancer
activities of sorafenib via mTORC1 inhibition.
AB - Aspirin is associated with a reduced risk of cancer and delayed progression of
malignant disease. Adenosine 5'-monophosphate (AMP)-activated protein kinase
(AMPK)-mTOR signaling is believed to partially contribute to these anticancer
effects, although the mechanism is unclear. In this study, we revealed the
mechanism underlying the effects of aspirin on AMPK-mTOR signaling, and described
a mechanism-based rationale for the use of aspirin in cancer therapy. We found
that aspirin inhibited mTORC1 signaling through AMPK-dependent and -independent
manners. Aspirin inhibited the AMPK-TSC pathway, thus resulting in the
suppression of mTORC1 activity. In parallel, it directly disrupted the mTOR
raptor interaction. Additionally, the combination of aspirin and sorafenib showed
synergetic effects via inhibiting mTORC1 signaling and the PI3K/AKT, MAPK/ERK
pathways. Aspirin and sorafenib showed synergetic anticancer efficacy in the SMMC
7721 model. Our study provides mechanistic insights and a mechanism-based
rationale for the roles of aspirin in cancer treatment.
PMID- 28687355
TI - Circulating tumour DNA (ctDNA) as a liquid biopsy for melanoma.
AB - Circulating tumour DNA (ctDNA) has emerged as a promising blood-based biomarker
for monitoring disease status of patients with advanced cancers. In melanoma,
ctDNA has been shown to have clinical value as an alternative tumour source for
the detection clinically targetable mutations for the assessment of response to
therapy. This review provides a critical summary of the evidence that gives
credence to the utility of ctDNA as a biomarker for monitoring of disease status
in advanced melanoma and the steps required for its implementation into clinical
settings.
PMID- 28687356
TI - Germline mutations in DNA repair genes predispose asbestos-exposed patients to
malignant pleural mesothelioma.
AB - Malignant pleural mesothelioma (MPM) is a rare, aggressive cancer caused by
asbestos exposure. An inherited predisposition has been suggested to explain
multiple cases in the same family and the observation that not all individuals
highly exposed to asbestos develop the tumor. Germline mutations in BAP1 are
responsible for a rare cancer predisposition syndrome that includes
predisposition to mesothelioma. We hypothesized that other genes involved in
hereditary cancer syndromes could be responsible for the inherited mesothelioma
predisposition. We investigated the prevalence of germline variants in 94 cancer
predisposing genes in 93 MPM patients with a quantified asbestos exposure. Ten
pathogenic truncating variants (PTVs) were identified in PALB2, BRCA1, FANCI,
ATM, SLX4, BRCA2, FANCC, FANCF, PMS1 and XPC. All these genes are involved in DNA
repair pathways, mostly in homologous recombination repair. Patients carrying
PTVs represented 9.7% of the panel and showed lower asbestos exposure than did
all the other patients (p = 0.0015). This suggests that they did not efficiently
repair the DNA damage induced by asbestos and leading to carcinogenesis. This
study shows that germline variants in several genes may increase MPM
susceptibility in the presence of asbestos exposure and may be important for
specific treatment.
PMID- 28687357
TI - Circular RNA MYLK as a competing endogenous RNA promotes bladder cancer
progression through modulating VEGFA/VEGFR2 signaling pathway.
AB - Accumulating evidences indicate that circular RNAs (circRNAs) play a vital role
in modulating gene expression. However, the mechanisms underlying circRNAs remain
largely elusive. Here, we screened circRNA and mRNA expression profiles of
bladder carcinoma (BC) using microarray analysis. We found that circRNA-MYLK and
VEGFA were significantly up-regulated and co-expressed in BC. Importantly,
circRNA-MYLK levels were related to the progression of stage and grade of BC.
Mechanistically, we demonstrated that circRNA-MYLK could directly bind to miR-29a
and relieve suppression for target VEGFA, which activated VEGFA/VEGFR2 signaling
pathway. Functionally, we found that ectopically expressing circRNA-MYLK
accelerated cell proliferation, migration, tube formation of HUVEC and rearranged
cytoskeleton. Moreover, up-regulating circRNA-MYLK promoted epithelial
mesenchymal transition (EMT). Whereas circRNA-MYLK knockdown decreased cell
proliferation, motility, and induced apoptosis. Finally, up-regulating circRNA
MYLK promoted the growth, angiogenesis and metastasis of BC xenografts. Taken
together, this study demonstrated for the first time that circRNA-MYLK might
function as competing endogenous RNA (ceRNA) for miR-29a, which could contribute
to EMT and the development of BC through activating VEGFA/VEGFR2 and downstream
Ras/ERK signaling pathway. Our data suggest that circRNA-MYLK would be a
promising target for BC diagnosis and therapy.
PMID- 28687358
TI - A Lactococcus lactis BFE920 feed vaccine expressing a fusion protein composed of
the OmpA and FlgD antigens from Edwardsiella tarda was significantly better at
protecting olive flounder (Paralichthys olivaceus) from edwardsiellosis than
single antigen vaccines.
AB - Edwardsiellosis is a major fish disease that causes a significant economic damage
in the aquaculture industry. Here, we assessed vaccine efficacy after feeding
oral vaccines to olive flounder (Paralichthys olivaceus), either L. lactis BFE920
expressing Edwardsiella tarda outer membrane protein A (OmpA), flagellar hook
protein D (FlgD), or a fusion antigen of the two. Feed vaccination was done twice
with a one-week interval. Fish were fed regular feed adsorbed with the vaccines.
Feed vaccination was given over the course of one week to maximize the
interaction between the feed vaccines and the fish intestine. Flounder fed the
vaccine containing the fusion antigen had significantly elevated levels T cell
genes (CD4-1, CD4-2, and CD8alpha), type 1 helper T cell (Th1) subset indicator
genes (T-bet and IFN-gamma), and antigen-specific antibodies compared to the
groups fed the single antigen-expressing vaccines. Furthermore, the superiority
of the fusion vaccine was also observed in survival rates when fish were
challenged with E. tarda: OmpA-FlgD-expressing vaccine (82.5% survival); FlgD
vaccine (55.0%); OmpA-vaccine (50%); WT L. lactis BFE920 (37.5%); Ctrl (10%). In
addition, vaccine-fed fish exhibited increased weight gain (~20%) and a decreased
feed conversion ratio (~20%) during the four week vaccination period. Flounder
fed the FlgD-expressing vaccine, either the single or the fusion form, had
significantly increased expression of TLR5M, IL-1beta, and IL-12p40, suggesting
that the FlgD may be a ligand of olive flounder TLR5M receptor or closely related
to the TLR5M pathway. In conclusion, the present study demonstrated that olive
flounder fed L. lactis BFE920 expressing a fusion antigen composed of E. tarda
OmpA and FlgD showed a strong protective effect against edwardsiellosis
indicating this may be developed as an E. tarda feed vaccine.
PMID- 28687359
TI - Identification and characterization of the lamprey Flotillin-1 gene with a role
in cell adhesion.
AB - Flotillin-1 is a kind of localize into specific cholesterol rich microdomains in
cellular membranes and highly conserved lipid rafts marker protein widely
distributed in animals and plants. It provides a platform for the reaction of
many proteins in signal transduction, as scaffolding plays an important role in
transmembrane signaling and cell adhesion. Here, Flotillin-1 protein from lamprey
was identified and characterized (designated as L-Flotillin-1). After a partial
cDNA sequence of L-Flotillin-1 was identified in a lamprey supraneural body cDNA
library, the full-length cDNA was obtained using 3'- and 5'-rapid amplification
of cDNA ends (RACE). L-Flotillin-1 encodes 424 amino acids and contains a
prohibitin domain and a flotillin repetitive area. The L-Flotillin-1 protein was
primarily distributed in kidney, supraneural body, gill, heart, liver and
intestine via real-time PCR and immunohistochemistry assays. Immunofluorescence
and western blot results showed that L-Flotillin-1 was considered to be used as a
marker protein of lamprey lipid rafts and exosomes. Furthermore, overexpression
of pEGFP-N1-L-Flotillin-1 induced the up-regulation of vascular cell adhesion
molecule-1 (VCAM-1) and intercellular cell adhesion molecule-1 (ICAM-1) mRNA
levels. These results indicated that the L-Flotillin-1 gene encodes Flotillin-1
protein that was used as a conserved marker protein and may play an important
role in cell adhesion, providing clues for understanding the universal functions
of Flotillin-1 proteins in other species and suggesting that these proteins could
serve as pattern recognition molecules in immunotherapy. We revealed that
Flotillin-1 protein of lamprey overexpression in human cells plays a prevalent
role in cell migration and provide new thought of treatment to diseases.
PMID- 28687360
TI - Extracellular matrix remodeling and matrix metalloproteinases (ajMMP-2 like and
ajMMP-16 like) characterization during intestine regeneration of sea cucumber
Apostichopus japonicus.
AB - Remodeling of extracellular matrix (ECM) regulated by matrix metalloproteinases
(MMPs) is essential for tissue regeneration. In the present study, we used
immunohistochemistry (IHC) techniques against ECM components to reveal changes of
ECM during intestine regeneration of Apostichopus japonicus. The expression of
collagen I and laminin reduced apparently from the eviscerated intestine, while
fibronectin exhibited continuous expression in all regeneration stages observed.
Meanwhile, we cloned two MMP genes from A. japonicus by RACE PCR. The full-length
cDNA of ajMMP-2 like is 2733bp and contains a predicted open reading frame (ORF)
of 1716bp encoding 572 amino acids. The full-length cDNA of ajMMP-16 like is
2705bp and contains an ORF of 1452bp encoding 484 amino acids. The predicted
protein sequences of each MMP contain two conserved domains, ZnMc_MMP and HX.
Homology and phylogenetic analysis revealed that ajMMP-2 like and ajMMP-16 like
share high sequence similarity with MMP-2 and MMP-16 from Strongylocentrotus
purpuratus, respectively. Then we investigated spatio-temporal expression of
ajMMP-2 like and ajMMP-16 like during different regeneration stages by qRT-PCR
and IHC. The expression pattern of them showed a roughly opposite trend from that
of ECM components. According to our results, a fibronectin-dominate temporary
matrix is created in intestine regeneration, and it might provide structural
integrity for matrix and promote cell movement. We also hypothesize that ajMMP-2
like and ajMMP-16 like could accelerate cell migration and regulate interaction
between ECM components and growth factors. This work provides new evidence of ECM
and MMPs involvement in sea cucumber regeneration.
PMID- 28687361
TI - Combined effects of diets and temperature on mitochondrial function, growth and
nutrient efficiency in rainbow trout (Oncorhynchus mykiss).
AB - A 4*3 factorial experiment was conducted to evaluate the effects of two dietary
protein sources (mixed fishmeal/plant protein-, and plant protein- based diet),
two dietary lipid levels (10% and 20%) and three water temperatures (10 degrees
C, 14 degrees C, and 18 degrees C) on the growth performance, nutrient
utilization efficiencies and mitochondrial enzyme complex activities in rainbow
trout Oncorhynchus mykiss (average weight+/-SD, 39.5+/-5g) over a 180day rearing
period. At the end of the experiment, weight gain (WG), condition factor (CF),
and feed efficiency (FE) were significantly affected by diet*temperature
interaction (P<0.05). Specific growth rate (SGR) was significantly affected by
increasing temperature (P<0.05). The plant protein-based diets led to a higher CF
than the mixed fishmeal/plant protein-based diets. The protein productive value
(PPV), protein efficiency ratio (PER), lipid efficiency ratio, (LER) and lipid
productive value (LPV) were all significantly affected by diet*temperature
interaction (P<0.05). The diet*temperature interaction also had significant
effects on mitochondrial enzyme complexes II, V and citrate synthase in the
liver, complexes II and IV in the intestine, and complex IV in the muscle
(P<0.05). Temperature had a significant main effect on the activity of the
enzymatic complexes I and III in the liver, complex III and citrate synthase in
the intestine, and complexes I, II, III, V and citrate synthase in the muscle
(P<0.05). Diet had a significant main effect on complexes I and III in the liver,
complexes II and III for the intestine and complexes I and II in the muscle
(P<0.05). The significant temperature x diet interaction observed has practical
ecological implications explicitly demonstrating how changes in temperature
regimens as anticipated in the rising global temperature can influence organismal
performance in relation to changes in dietary formulations (replacing fishmeal
based diet with plant protein based ingredients). To illustrate the practical
application of the observations from this study, the most economical and cost
effective way to produce rainbow trout would be to use 40/10PP diet at 14 degrees
C because fish fed this treatment had a weight gain comparable to that of the
fish fed the more expensive experimental diets (40/10 FM/PP, 40/20 FM/PP, and
40/20 PP).
PMID- 28687362
TI - The unexpected function of a highly conserved YXXPhi motif in HCV core protein.
AB - Hepatitis C virus (HCV) is an RNA positive strand virus, member of the
Flaviviridae family. The HCV viral particle is composed of a capsid containing
the genome, surrounded by an endoplasmic reticulum (ER)-derived lipid bilayer
where E1 and E2 are assembled as heterodimers. However, different forms of viral
particles have been identified in the serum of HCV-infected patients, including
non-enveloped particles. Previous reports have demonstrated that HCV non
enveloped capsid-like particles (HCVne) can be generated by HCV core protein
sequence. This sequence possesses a highly conserved UpsilonChiChiPhi motif and
distal di-leucine motifs that confer primary endocytosis signals, enabling HCVne
to enter hepatic cells via clathrin-mediated endocytosis. Although HCV core's
primary function is to encapsidate the viral genome, it also interacts with a
variety of cellular proteins in order to regulate host cell functions such as
gene transcription, lipid metabolism, apoptosis and several signaling pathways.
In this report, we demonstrate that the YXXPhi motif of HCV core protein is
crucial for the architectural integrity of the particulate form of HCVne.
Moreover, we show that the YXXPhi motif in the HCV core sequence plays a pivotal
role in the signaling events following HCVne clathrin-mediated endocytosis by
inducing the AP-2 clathrin adaptor protein, which in turn redirect HCVne
trafficking to the lipid droplets (LDs) via the endosomal-lysosomal pathway.
HCVne and LDs co-localization affects the HCV life cycle by enhancing viral
replication.
PMID- 28687363
TI - Percutaneous screw fixation of the iliosacral joint: A case-based preoperative
planning approach reduces operating time and radiation exposure.
AB - INTRODUCTION: A preoperative planning approach for percutaneous screw fixation of
the iliosacral joint provides specific entry points (EPs) and aiming points (APs)
of intraosseous screw pathways (as defined by CT scans) for lateral fluoroscopic
projections used intraoperatively. The potential to achieve the recommended EPs
and APs, to obtain an ideal screw position (perpendicular to the iliosacral
joint), to avoid occurrence of extraosseous screw misplacement, to reduce the
operating time and the radiation exposure by utilizing this planning approach
have not been described yet. METHODS: On preoperative CT scans of eight human
cadaveric specimen individual EPs and APs were identified and transferred to the
lateral fluoroscopic projection using a coordinate system with the zero-point in
the center of the posterior cortex of the S1 vertebral body (x-axis parallel to
upper S1 endplate). Distances were expressed in relation to the anteroposterior
distance of the S1 upper endplate (in%). In each specimen on one side a screw was
placed with provided EP and AP (New Technique) whereas at the contralateral side
a screw was placed without given EP and AP (Conventional Technique). Both
techniques were compared using postoperative CT scans to assess distances between
predefined EPs and APs and the actually obtained EPs and APs, screw angulations
in relation to the iliosacral joint in coronal and axial planes and the
occurrence of any extraosseous screw misplacement. The "operating time (OT)" and
the "time under fluoroscopy (TUF)" were recorded. Statistical analysis was
performed by the Wilcoxon signed-rank test. RESULTS: EPs were realized
significantly more accurate using the new technique in vertical direction. The
screw positions in relation to the iliosacral joint showed no significant
difference between both techniques. Both techniques had one aberrantly placed
screw outside the safe corridor. The (mean+/-SD) "OT" and the (mean+/-SD) "TUF"
were significantly decreased using the new technique compared to the conventional
technique (OT: 7.6+/-2min versus 13.1+/-5.8min, p=0.012; TUF: 1.5+/-0.8min versus
2.2+/-1.1min). CONCLUSION: The presented preoperative planning approach increases
the accuracy in percutaneous screw fixation of the iliosacral joint, reduces
operating time and minimizes radiation exposure to patient and staff.
PMID- 28687364
TI - A success story of Pakistan: The country at the verge of winning the battle
against polio.
PMID- 28687365
TI - Efficacy of Botulinum toxin A for the treatment of Bladder pain syndrome: A
systematic review.
AB - OBJECTIVES: To determine the efficacy and safety of BTX-A, compared with other
interventions for the treatment of BPS to improve quality of life. METHODS: This
systematic review fulfils all the requirements of the Cochrane manual and PRISMA
reporting guidelines. The PROSPERO registration number is:
CRD42016039480.Clinical trials without language discrimination were included. BPS
patients over 18 y/o that were treated with BTX-A were included. Studies were
searched in published databases and no published literature from inception to the
present day. Risk of bias analysis was done using the Cochrane risk of bias tool.
RESULTS: 88 articles were found with the designed search strategies. After
exclusions, four studies were included in the qualitative analyses. Kasyan et
al., 2012 compared BTX-A with hydrodistention. Manning et al., 2014 compared the
injection of BTX-A with the injection of normal saline in previously
hydrodistended bladders. In both cases, primary end point was measured by the
O'Leary-Sant questionnaire score. El-Bahnasy et al., 2009 compared BTX-A with BCG
administration, through Global Response Assessment. Kuo et al., 2015 compared
hydrodistention plus suburothelial injections of BTX-A with hydrodistension plus
normal saline injections. Reduction in pain was estimated by VAS bladder pain
score. A similar efficacy to their controls had been found in Kasyan and Manning
studies. El-Bahnasy had found improvement in BTX-A in all parameters. Kuo el al.
2015, found a significantly reduction in pain in the BTX-A group. Regarding the
risk of bias, three studies did not have adequate descriptions of selection,
performance and detection bias. The study of Manning had low risk of selection,
attrition and reporting bias. CONCLUSION: There is not enough evidence to
conclude the efficacy of BTX-A for the treatment of interstitial cystitis to
improve quality of life.
PMID- 28687366
TI - The era of the novel oral anticoagulants in Portugal.
PMID- 28687367
TI - The relationship between erythrocyte membrane fatty acid levels and cardiac
autonomic function in obese children.
AB - OBJECTIVE: Childhood obesity is a worldwide health concern. Studies have shown
autonomic dysfunction in obese children. The exact mechanism of this dysfunction
is still unknown. The aim of this study was to assess the relationship between
erythrocyte membrane fatty acid (EMFA) levels and cardiac autonomic function in
obese children using heart rate variability (HRV). METHODS: A total of 48 obese
and 32 healthy children were included in this case-control study. Anthropometric
and biochemical data, HRV indices, and EMFA levels in both groups were compared
statistically. RESULTS: HRV parameters including standard deviation of normal-to
normal R-R intervals (NN), root mean square of successive differences, the number
of pairs of successive NNs that differ by >50 ms (NN50), the proportion of NN50
divided by the total number of NNs, high-frequency power, and low-frequency power
were lower in obese children compared to controls, implying parasympathetic
impairment. Eicosapentaenoic acid and docosahexaenoic acid levels were lower in
the obese group (p<0.001 and p=0.012, respectively). In correlation analysis, in
the obese group, body mass index standard deviation and linoleic acid,
arachidonic acid, triglycerides, and high-density lipoprotein levels showed a
linear correlation with one or more HRV parameter, and age, eicosapentaenoic
acid, and systolic and diastolic blood pressure correlated with mean heart rate.
In linear regression analysis, age, dihomo-gamma-linolenic acid, linoleic acid,
arachidonic acid, body mass index standard deviation, systolic blood pressure,
triglycerides, low-density lipoprotein and high-density lipoprotein were related
to HRV parameters, implying an effect on cardiac autonomic function. CONCLUSION:
There is impairment of cardiac autonomic function in obese children. It appears
that levels of EMFAs such as linoleic acid, arachidonic acid and dihomo-gamma
linolenic acid play a role in the regulation of cardiac autonomic function in
obese children.
PMID- 28687368
TI - New CMS medicare coverage decision memorandum supervised exercise therapy for
symptomatic PAD.
PMID- 28687369
TI - Corrigendum to "Exemplars in advanced practice gerontological nursing: A GAPNA
series GAPNA consensus statement proficiency 9" [Geriatr Nurs 38 (2) (2017) 165
167].
PMID- 28687370
TI - [The epidemiology of pharmacologically treated attention deficit hyperactivity
disorder (ADHD) in the Region of Murcia, Spain: Differences by gender, age and
location of residence].
AB - INTRODUCTION: Attention deficit hyperactivity disorder (ADHD) is the most
frequent disorder in childhood and adolescence, and is seen as a public health
problem. The recommended treatment includes pharmacological and psychosocial
treatment. The aim of this work was to study the changes in the prescribing of
the medicines used in ADHD treatment in the Region of Murcia, as well as their
socio-demographic variability. METHOD: A retrospective observational study was
conducted using the dispensing of medicines for ADHD treatment by means of
prescription in the Region of Murcia from 2010 to 2014. The consumption rates
were determined as defined daily doses (DDD) per thousand inhabitants/day (DHD),
stratified by gender and age. The reasons for prevalence of treatment by gender
were also determined by comparing male and female consumption rates. RESULTS: The
consumption of medicines for ADHD treatment had almost doubled in the period
studied, from 5.58 DHD and 3.39 DHD in 2010 to 9.34 DHD and 6.71 DHD in 2014, for
the age range of 10-14 and 15-19, respectively. Boys from 10-14 showed the
highest consumption rates, showing a high geographical variability with less
consumption in rural areas. CONCLUSION: The results showed a large increase in
the use of medicines for ADHD treatment in the Region of Murcia, although the
consumption rates are still lower than in other Autonomous Communities or
neighbouring countries. A wide geographical variability was found, with a higher
consumption in adolescents from urban areas.
PMID- 28687371
TI - Body weight loss, effective satiation and absence of homeostatic neuropeptide
compensation in male Sprague Dawley rats schedule fed a protein crosslinked diet.
AB - Food structure contributes to the induction of satiation and the maintenance of
satiety following intake of a meal. There is evidence from human studies that
protein-crosslinking of a milk-protein based meal may enhance satiety, but the
mechanism underpinning this effect is unknown. We investigated whether a rat
model would respond in a similar manner and might provide mechanistic insight
into enhanced satiety by structural modification of a food source. Rats were
schedule fed a modified AIN-93M based diet in a liquid form or protein
crosslinked to produce a soft-solid form. This was compared to a modified AIN-93M
solid diet. Average daily caloric intake was in the order solid > liquid >
crosslinked. Body composition was unaltered in the solid group, but there was a
loss of fat in the liquid group and a loss of lean and fat tissue in the
crosslinked group. Compared to rats fed a solid diet, acute responses in
circulating GLP-1, leptin and insulin were eliminated or attenuated in rats fed a
liquid or crosslinked diet. Quantification of homeostatic neuropeptide expression
in the hypothalamus showed elevated levels of Npy and Agrp in rats fed the liquid
diet. Measurement of food intake after a scheduled meal indicated that reduced
energy intake of liquid and crosslinked diets is not due to enhancement of
satiety. When continuously available ad-libitum, rats fed a liquid diet showed
reduced weight gain despite greater 24 h caloric intake. During the dark phase,
caloric intake was reduced, but compensated for during the light phase. We
conclude that structural modification from a liquid to a solidified state is
beneficial for satiation, with less of a detrimental effect on metabolic
parameters and homeostatic neuropeptides.
PMID- 28687372
TI - Effects of a free-choice high-fat high-sugar diet on brain PER2 and BMAL1 protein
expression in mice.
AB - The suprachiasmatic nucleus (SCN) times the daily rhythms of behavioral processes
including feeding. Beyond the SCN, the hypothalamic arcuate nucleus (ARC),
involved in feeding regulation and metabolism, and the epithalamic lateral
habenula (LHb), implicated in reward processing, show circadian rhythmic
activity. These brain oscillators are functionally coupled to coordinate the
daily rhythm of food intake. In rats, a free choice high-fat high-sugar (fcHFHS)
diet leads to a rapid increase of calorie intake and body weight gain.
Interestingly, under a fcHFHS condition, rats ingest a similar amount of sugar
during day time (rest phase) as during night time (active phase), but keep the
rhythmic intake of regular chow-food. The out of phase between feeding patterns
of regular (chow) and highly rewarding food (sugar) may involve alterations of
brain circadian oscillators regulating feeding. Here, we report that the fcHFHS
diet is a successful model to induce calorie intake, body weight gain and fat
tissue accumulation in mice, extending its effectiveness as previously reported
in rats. Moreover, we observed that whereas in the SCN the day-night difference
in the PER2 clock protein expression was similar between chow-fed and fcHFHS-fed
animals, in the LHb, this day-night difference was altered in fcHFHS-exposed
animals compared to control chow mice. These findings confirm previous
observations in rats showing disrupted daily patterns of feeding behavior under a
fcHFHS diet exposure, and extend our insights on the effects of the diet on
circadian gene expression in brain clocks.
PMID- 28687374
TI - Radiosurgery for resected brain metastases-a new standard of care?
PMID- 28687373
TI - IL-33 and the intestine: The good, the bad, and the inflammatory.
AB - Interleukin-33 (IL-33) is a member of the IL-1 cytokine family that has been
widely studied since its discovery in 2005 for its dichotomous functions in
homeostasis and inflammation. IL-33, along with its receptor suppression of
tumorigenicity 2 (ST2), has been shown to modulate both the innate and adaptive
immune system. Originally, the IL-33/ST2 signaling axis was studied in the
context of inducing type 2 immune responses with the expression of ST2 by T
helper 2 (TH2) cells. However, the role of IL-33 is not limited to TH2 responses.
Rather, IL-33 is a potent activator of TH1 cells, group 2 innate lymphoid cells
(ILC2s), regulatory T (Treg) cells, and CD8+ T cells. The intestine is uniquely
important in this discussion, as the intestinal epithelium is distinctively
positioned to interact with both pathogens and the immune cells housed in the
mucosa. In the intestine, IL-33 is expressed by the pericryptal fibroblasts and
its expression is increased particularly in disease states. Moreover, IL-33/ST2
signaling aberrancy is implicated in the pathogenesis of inflammatory bowel
disease (IBD). Accordingly, for this review, we will focus on the role of IL-33
in the regulation of intestinal immunity, involvement in intestinal disease, and
implication in potential therapeutics.
PMID- 28687375
TI - Post-operative stereotactic radiosurgery versus observation for completely
resected brain metastases: a single-centre, randomised, controlled, phase 3
trial.
AB - BACKGROUND: After brain metastasis resection, whole brain radiotherapy decreases
local recurrence, but might cause cognitive decline. We did this study to
determine if stereotactic radiosurgery (SRS) to the surgical cavity improved time
to local recurrence compared with that for surgical resection alone. METHODS: In
this randomised, controlled, phase 3 trial, we recruited patients at a single
tertiary cancer centre in the USA. Eligible patients were older than 3 years, had
a Karnofsky Performance Score of 70 or higher, were able to have an MRI scan, and
had a complete resection of one to three brain metastases (with a maximum
diameter of the resection cavity <=4 cm). Patients were randomly assigned (1:1)
with a block size of four to either SRS of the resection cavity (within 30 days
of surgery) or observation. Patients were stratified by histology of the primary
tumour, metastatic tumour size, and number of metastases. The primary endpoint
was time to local recurrence in the resection cavity, assessed by blinded central
review of brain MRI scans by the study neuroradiologist in the modified intention
to-treat population that analysed patients by randomised allocation but excluded
patients found ineligible after randomisation. Participants and other members of
the treatment team (excluding the neuroradiologist) were not masked to treatment
allocation. The trial is registered with ClinicalTrials.gov, number NCT00950001,
and is closed to new participants. FINDINGS: Between Aug 13, 2009, and Feb 16,
2016, 132 patients were randomly assigned to the observation group (n=68) or SRS
group (n=64), with 128 patients available for analysis; four patients were
ineligible (three from the SRS group and one from the observation group). Median
follow-up was 11.1 months (IQR 4.8-20.4). 12-month freedom from local recurrence
was 43% (95% CI 31-59) in the observation group and 72% (60-87) in the SRS group
(hazard ratio 0.46 [95% CI 0.24-0.88]; p=0.015). There were no adverse events or
treatment-related deaths in either group. INTERPRETATION: SRS of the surgical
cavity in patients who have had complete resection of one, two, or three brain
metastases significantly lowers local recurrence compared with that noted for
observation alone. Thus, the use of SRS after brain metastasis resection could be
an alternative to whole-brain radiotherapy. FUNDING: National Institutes of
Health.
PMID- 28687378
TI - All tumours are rare, but some are rarer than others.
PMID- 28687379
TI - Moderate Sedation Changes for Bronchoscopy in 2017.
AB - The reimbursement for procedures using moderate (conscious) sedation has changed
significantly as of January 1, 2017. Due to the increasing use of anesthesia
services to provide moderate sedation during endoscopy, the Centers for Medicare
& Medicaid Services made the decision to remove work relative value units from
many of the services requiring moderate sedation, including the bronchoscopy
codes. If a bronchoscopist provides moderate sedation to a patient without using
anesthesia services or another qualified provider, that work (and revenue) can be
reclaimed by using the relevant codes. An understanding of the recent changes in
coding and billing is essential for appropriate reimbursement.
PMID- 28687377
TI - Postoperative stereotactic radiosurgery compared with whole brain radiotherapy
for resected metastatic brain disease (NCCTG N107C/CEC.3): a multicentre,
randomised, controlled, phase 3 trial.
AB - BACKGROUND: Whole brain radiotherapy (WBRT) is the standard of care to improve
intracranial control following resection of brain metastasis. However,
stereotactic radiosurgery (SRS) to the surgical cavity is widely used in an
attempt to reduce cognitive toxicity, despite the absence of high-level
comparative data substantiating efficacy in the postoperative setting. We aimed
to establish the effect of SRS on survival and cognitive outcomes compared with
WBRT in patients with resected brain metastasis. METHODS: In this randomised,
controlled, phase 3 trial, adult patients (aged 18 years or older) from 48
institutions in the USA and Canada with one resected brain metastasis and a
resection cavity less than 5.0 cm in maximal extent were randomly assigned (1:1)
to either postoperative SRS (12-20 Gy single fraction with dose determined by
surgical cavity volume) or WBRT (30 Gy in ten daily fractions or 37.5 Gy in 15
daily fractions of 2.5 Gy; fractionation schedule predetermined for all patients
at treating centre). We randomised patients using a dynamic allocation strategy
with stratification factors of age, duration of extracranial disease control,
number of brain metastases, histology, maximal resection cavity diameter, and
treatment centre. Patients and investigators were not masked to treatment
allocation. The co-primary endpoints were cognitive-deterioration-free survival
and overall survival, and analyses were done by intention to treat. We report the
final analysis. This trial is registered with ClinicalTrials.gov, number
NCT01372774. FINDINGS: Between Nov 10, 2011, and Nov 16, 2015, 194 patients were
enrolled and randomly assigned to SRS (98 patients) or WBRT (96 patients). Median
follow-up was 11.1 months (IQR 5.1-18.0). Cognitive-deterioration-free survival
was longer in patients assigned to SRS (median 3.7 months [95% CI 3.45-5.06], 93
events) than in patients assigned to WBRT (median 3.0 months [2.86-3.25], 93
events; hazard ratio [HR] 0.47 [95% CI 0.35-0.63]; p<0.0001), and cognitive
deterioration at 6 months was less frequent in patients who received SRS than
those who received WBRT (28 [52%] of 54 evaluable patients assigned to SRS vs 41
[85%] of 48 evaluable patients assigned to WBRT; difference -33.6% [95% CI -45.3
to -21.8], p<0.00031). Median overall survival was 12.2 months (95% CI 9.7-16.0,
69 deaths) for SRS and 11.6 months (9.9-18.0, 67 deaths) for WBRT (HR 1.07 [95%
CI 0.76-1.50]; p=0.70). The most common grade 3 or 4 adverse events reported with
a relative frequency greater than 4% were hearing impairment (three [3%] of 93
patients in the SRS group vs eight [9%] of 92 patients in the WBRT group) and
cognitive disturbance (three [3%] vs five [5%]). There were no treatment-related
deaths. INTERPRETATION: Decline in cognitive function was more frequent with WBRT
than with SRS and there was no difference in overall survival between the
treatment groups. After resection of a brain metastasis, SRS radiosurgery should
be considered one of the standards of care as a less toxic alternative to WBRT
for this patient population. FUNDING: National Cancer Institute.
PMID- 28687376
TI - Burden and centralised treatment in Europe of rare tumours: results of
RARECAREnet-a population-based study.
AB - BACKGROUND: Rare cancers pose challenges for diagnosis, treatments, and clinical
decision making. Information about rare cancers is scant. The RARECARE project
defined rare cancers as those with an annual incidence of less than six per 100
000 people in European Union (EU). We updated the estimates of the burden of rare
cancers in Europe, their time trends in incidence and survival, and provide
information about centralisation of treatments in seven European countries.
METHODS: We analysed data from 94 cancer registries for more than 2 million rare
cancer diagnoses, to estimate European incidence and survival in 2000-07 and the
corresponding time trends during 1995-2007. Incidence was calculated as the
number of new cases divided by the corresponding total person-years in the
population. 5-year relative survival was calculated by the Ederer-2 method. Seven
registries (Belgium, Bulgaria, Finland, Ireland, the Netherlands, Slovenia, and
the Navarra region in Spain) provided additional data for hospitals treating
about 220 000 cases diagnosed in 2000-07. We also calculated hospital volume
admission as the number of treatments provided by each hospital rare cancer group
sharing the same referral pattern. FINDINGS: Rare cancers accounted for 24% of
all cancers diagnosed in the EU during 2000-07. The overall incidence rose
annually by 0.5% (99.8% CI 0.3-0.8). 5-year relative survival for all rare
cancers was 48.5% (95% CI 48.4 to 48.6), compared with 63.4% (95% CI 63.3 to
63.4) for all common cancers. 5-year relative survival increased (overall 2.9%,
95% CI 2.7 to 3.2), from 1999-2001 to 2007-09, and for most rare cancers, with
the largest increases for haematological tumours and sarcomas. The amount of
centralisation of rare cancer treatment varied widely between cancers and between
countries. The Netherlands and Slovenia had the highest treatment volumes.
INTERPRETATION: Our study benefits from the largest pool of population-based
registries to estimate incidence and survival of about 200 rare cancers.
Incidence trends can be explained by changes in known risk factors, improved
diagnosis, and registration problems. Survival could be improved by early
diagnosis, new treatments, and improved case management. The centralisation of
treatment could be improved in the seven European countries we studied. FUNDING:
The European Commission (Chafea).
PMID- 28687380
TI - Patient and Family Engagement in Designing and Implementing a Weaning Trial: A
Novel Research Paradigm in Critical Care.
AB - The call for meaningful patient and family engagement in research has recently
gained considerable momentum. This article defines patient and family engagement
broadly and specifically in clinical research. Using a multicenter, North
American weaning trial as an exemplar, we describe our early experiences as
clinical researchers with patient and family engagement. The role of our Patient
and Family Advisory Committee in trial design and implementation is illustrated.
Through our experiences, we share our insights regarding the perceived
opportunities and also highlight some challenges associated with engaging
patients and family engagement in critical care research. Although "engagement
science" is in its infancy, engaging patients and families in research holds
promise as a novel research paradigm that will not only provide new insights into
the questions, methods, and outcomes used in ICU research, but it will also make
investments in research more accountable and ensure a strong "patient- and family
centered focus" of our research.
PMID- 28687381
TI - Operative Procedure of Anterior Commissure for Type II Thyroplasty.
AB - OBJECTIVE: We reviewed the clinical anatomy of the anterior commissure and
examined the effectiveness of a specialized spreader developed for optimal,
efficient spreading of the thyroid cartilage in type II thyroplasty. STUDY DESIGN
AND METHODS: The present study was a multicenter retrospective study of patients
with spasmodic dysphonia who underwent a primary operation either before or after
the introduction of a specialized spreader (in 2008 or 2014, respectively). In
these patients, we examined the size of the titanium bridge used, the presence of
perforation of the mucosa directly superior to the anterior commissure, and
postoperative glottic findings. RESULTS: The sample comprised 39 and 40 patients
who underwent surgery in 2008 and 2014, respectively. The mean size of the
titanium bridge used during surgery was significantly smaller in 2014 (2.9 mm)
than in 2008 (3.81 mm). Perforation of the laryngeal mucosa occurred in 13
patients in 2008 but occurred in only one patient in 2014. Based on glottic
findings, spreading the thyroid cartilage using the specialized spreader was
deemed to yield an effective glottic gap. CONCLUSIONS: In type II thyroplasty,
the handling of the anterior commissure is the most important point. It is
necessary to split the tendon and to spread the glottis while the tendon is
joined with the cartilage. For this purpose, a specialized spreader was made. The
use of a specialized spreader renders separation around the anterior commissure
unnecessary, enabling minimally invasive spreading of the thyroid cartilage and
thereby improving phonation.
PMID- 28687382
TI - Response to Aichinger and Kubin Re: Letter to the Editor "Acoustic and Perceptual
Classification of Within-Sample Normal, Intermittently Dysphonic, and
Consistently Dysphonic Voice Types".
PMID- 28687383
TI - Isolation and characterization of lignins from wheat straw: Application as binder
in lithium batteries.
AB - Three different lignin-rich fractions have been used as binder material for
electrodes in rechargeable lithium batteries. Lignin samples were obtained
through three different pulping processes; kraft, soda and organosolv pulping
processes, using wheat straw as raw material. Physico-chemical characterization
of three types of lignins was evaluated. Characterization has been performed
using Fourier transform infrared spectroscopy (FTIR) and 31P NMR Spectroscopy to
analyse the functional groups; gel permeation chromatography (GPC) for
determining molar mass distribution (MWD), and thermogravimetric analysis (TGA)
to follow the thermal behaviour. Electrodes containing lignin or poly vinylidene
fluoride (PVDF) were tested electrochemically. The three different lignin samples
exhibited excellent performance as binder, retaining the specific capacity after
50 cycles at a current density of 100mAg-1. These results show that lignin could
be used as a low-cost and environmental binder, replacing the PVDF polymer in
electrodes for energy storage applications.
PMID- 28687384
TI - The identification of new substrates of human DHRS7 by molecular modeling and in
vitro testing.
AB - Human DHRS7 (SDR34C1) is one of insufficiently described enzymes of the short
chain dehydrogenase/reductase superfamily. The members of this superfamily often
play an important pato/physiological role in the human body, participating in the
metabolism of diverse substrates (e.g. retinoids, steroids, xenobiotics). A
systematic approach to the identification of novel, physiological substrates of
DHRS7 based on a combination of homology modeling, structure-based virtual
screening and experimental evaluation has been used. Three novel substrates of
DHRS7 (dihydrotestosterone, benzil and 4,4'-dimetylbenzil) have been described.
PMID- 28687385
TI - The use of cross-linked chitosan beads for nutrients (nitrate and orthophosphate)
removal from a mixture of P-PO4, N-NO2 and N-NO3.
AB - A hydrogel chitosan sorbent ionically cross-linked with sodium citrate and
covalently cross-linked with epichlorohydrin was used to remove nutrients from an
equimolar mixture of P-PO4, N-NO2 and N-NO3. The scope of the study included,
among other things, determination of the influence of pH on nutrient sorption
effectiveness, nutrient sorption kinetics as well as determination of the maximum
sorption capacity of cross-linked chitosan sorbents regarding P-PO4 (H2PO4-,
HPO42-), N-NO2 (HNO2, NO2-), and N-NO3 (NO3-). The effect of the type of the
cross-linking agent on the affinity of the modified chitosan to each nutrient was
studied as well. The kinetics of nutrient sorption on the tested chitosan
sorbents was best described with the pseudo-second order model. The model of
intramolecular diffusion showed that P-PO4, N-NO2 and N-NO3 sorption on cross
linked hydrogel chitosan beads proceeded in two phases. The best sorbent of
nutrients turned out to be chitosan cross-linked covalently with epichlorohydrin;
with P-PO4, N-NO2 and N-NO3 sorption capacity reaching: 1.23, 0.94 and
0.76mmol/g, respectively (total of 2.92mmol/g). For comparison, the sorption
capacity of chitosan cross-linked ionically with sodium citrate was: 0.43, 0.39
and 0.39mmol/g for P-PO4, N-NO2 and N-NO3, respectively (total of 1.21mmol/g).
PMID- 28687386
TI - Amino acid composition in determination of collagen origin and assessment of
physical factors effects.
AB - The amino acid composition of collagen is a characteristic feature of this
protein. Collagen, irrespective of its origin, contains 19 amino acids, including
hydroxyproline which does not occur in other proteins. Its atypical amino acid
composition is characterized by high content of proline and glycine, as well as
the absence of cysteine. This paper shows the comparison of qualitative
composition of amino acids of fish skin (FS) collagen, bovine Achilles tendon
(BAT) collagen, and bone collagen. Results demonstrate that FS collagen as well
as BAT collagen contains no cysteine and significantly different amount of
hydroxyproline. In BAT collagen hydroxyproline content is 30% higher than
hydroxyproline content of FS collagen. In bone collagen the amount of
hydroxyproline is two times more than in FS collagen. Furthermore, it is shown
that sensitivity to radiation of individual amino acids varies and depends on the
absorbed dose of ionizing radiation. The changes observed in the amino acid
composition become very intense for the doses of 500kGy and 1000kGy.
PMID- 28687387
TI - Hybrid hydrogels with high strength and biocompatibility for bone regeneration.
AB - The development of hydrogels for bone regeneration has highlighted the challenge
that load-bearing hydrogels need to be biocompatible while achieving high
strength. Several approaches have been reported to improve the toughness of
hydrogels, but achieving high toughness and biocompatibility simultaneously
remains a challenge. Here we report a polyacrylic acid/alginate/demineralized
bone matrix (PAA/Alg/DBM) hybrid double network hydrogel, which was synthesized
by a two-step sequential polymerization with embedded DBM, possessing both high
strength and biocompatibility. With the persistence of DBM, it can promote the
synthesis of VEGF and bFGF and the ALP activity of MG63 cells on hydrogel. All
the results suggest that this hybrid double network hydrogel have potential for
future application in bone regeneration.
PMID- 28687388
TI - Flaxseed gum in combination with lemongrass essential oil as an effective edible
coating for ready-to-eat pomegranate arils.
AB - Flaxseed gum (FSG) in combination with lemongrass essential oil (LGEO) was
investigated for coating of ready-to-eat pomegranate arils. FSG was used at 0.3%
and 0.6% concentrations and with both concentrations LGEO was incorporated at
levels of 0ppm, 200ppm, 500ppm and 800ppm. Changes in headspace gases,
physicochemical, microbiological and sensory attributes of pomegranate arils
stored at 5 degrees C were studied on different days of analysis during the 12day
storage period. Coatings containing LGEO were effective in reducing total plate
count and yeast and mold populations. Increasing LGEO concentrations in the
coatings resulted in more decline in microbial populations. Reduced weight loss
occurred in coated samples as compared to uncoated (control) sample. Coated
samples showed a gradual decrease in ripening index in contrast with control
where a significantly higher decline was observed. Total soluble solids, pH and
titratable acidity significantly varied over the storage period. Color change
(DeltaE) for control increased steeply over the storage time in comparison to
coated samples. Furthermore, chroma decreased while as hue angle increased over
time.
PMID- 28687389
TI - Preparation of functional chitosan-based nanocomposite films containing ZnS
nanoparticles.
AB - In this study, nanocomposite films were synthesized by chitosan (CH), PVA, ZnS,
sulfosuccinic acid, and plasticizers. The nanocomposite films were cross-linked
by the heat curing process. ZnS was synthesized by the reaction of Zn(CH3COO)2
and Na2S2O3.5H2O in aqueous solution via a template-free hydrothermal process.
The prepared ZnS and CH/PVA nanocomposite films were characterized by X-ray
diffraction, Fourier transform IR spectroscopy, and scanning electronic
microscopy. The results of this study confirmed the presence of specific peaks of
ZnS in the prepared nanocomposite films, and the intensity of these peaks
increased with increasing ZnS contents. Tensile strength, elongation at break,
water barrier properties, and thermal properties of the prepared nanocomposite
films were also investigated, indicating that the addition of ZnS nanoparticles
improved the physical and thermal properties. In addition, the photocatalytic
degradability of the prepared films containing ZnS nanoparticles was evaluated
using 2,4-dichlorophenoxyacetic acid and methyl orange.
PMID- 28687390
TI - Physicochemical stability of curcumin emulsions stabilized by Ulva fasciata
polysaccharide under different metallic ions.
AB - The aim of this research was to investigate the effect of metallic ions (Na+,
Ca2+, K+ and Mg2+) on the physicochemical stability of curcumin emulsions
stabilized by Ulva fasciata polysaccharide (UFP). Mean droplet diameter, PdI,
zeta-potential, microscopic morphology, and rheological properties of curcumin
emulsion stabilized by UFP were investigated. The results showed that different
metal ions had significantly different effects on the stability of emulsion. When
the effect of Mg2+ was compared with others, it was found that Mg2+ had a
pronounced effect on emulsion stability. As for z-average size and PdI, they
changed significantly for metallic ions with higher valence. According to the
rheology test, Ca2+ could mediate the gelation of UFP emulsions. Besides, with an
increase of ionic concentration, the retention rate of curcumin was reduced. In
comparison with gum Arabic, the UFP revealed better stability under different
metallic ions and ionic concentration at same concentration.
PMID- 28687391
TI - Using a bacterial fucose-rich polysaccharide as encapsulation material of
bioactive compounds.
AB - The potential of a bacterial exopolysaccharide named FucoPol, produced by the
bacterium Enterobacter A47, as encapsulation matrix was explored. Spherical
capsules with a smooth surface were produced by spray drying. The obtained
microcapsules had average diameters ranging from 0.5 to 26.7MUm and presented
thin walls (thickness from 222 to 1094nm). The capsules were loaded with two
bioactive compounds: gallic acid (GA) and oregano essential oil (OEO). Both
bioactive materials were encapsulated in FucoPol particles, retaining their
antioxidant activity after the drying process. Release studies showed that GA
release in simulated gastric and intestinal fluids was faster than that of OEO,
envisaging that the latter had established stronger interactions with the polymer
matrix. These results suggest that FucoPol has a good potential for use as
encapsulating material of bioactive compounds for application in several areas,
including food, cosmetic or pharmaceutical products.
PMID- 28687392
TI - Characterization and in vitro anticancer properties of chitosan-microencapsulated
flavan-3-ols-rich grape seed extracts.
AB - Studies have fully demonstrated that a diet rich in fruit and vegetables may
reduce the incidence of tumors. In particular, Grape Seed Extract (GSE) has been
shown to carry on chemopreventive and antitumor activity thanks to the numerous
beneficial substances it contains. The purpose of this work was to create a
biocompatible matrix containing GSE in order to obtain microparticles able to
modulate its biopharmaceutical parameters. The spray-drying technique was chosen
in order to realize chitosan microparticles characterized by a mean diameter of 4
10MUm and a positive surface charge that decreased after GSE encapsulation. The
evaluation of the pharmacological activity of the GSE and these GSE-loaded
chitosan microparticles on different cancer cells together with CLSM
investigation evidenced an increase in the antitumor effect promoted by the
polysaccharide as a consequence of the enhanced cell interaction. Therefore GSE
loaded chitosan microparticles may be an innovative drug delivery system useful
for the treatment of certain cancer-related diseases.
PMID- 28687393
TI - A promising wound dressing material with excellent cytocompatibility and
proangiogenesis action for wound healing: Strontium loaded Silk fibroin/Sodium
alginate (SF/SA) blend films.
AB - Effectively stimulating angiogenesis is great challenge in wound care management.
It's necessary to develop a new wound dressing with angiogenic capacity.
Therefore, strontium loaded SF/SA blend films were prepared as a potential wound
dressing material, and their physicochemical and bioactive properties were
evaluated. The strontium loaded SF/SA blend films (especially the strontium
loaded SF/SA blend films prepared by treating with 5mg/ml Sir solution) could
meet the needs of a wound dressing such as water absorption, water vapor
transmission rate, mechanical properties and fibroblasts-cytocompatibility.
What's more, these films had a potential to induce angiogenesis by improving
vascular VEGF and bFGF protein secretion, which was important for wound
dressings. Based on the previous studies, we could infer this novel wound
dressing possesses the antibacterial activity. The present study suggests that
the strontium loaded SF/SA blend film prepared by treating with 5mg/ml Sr
solution are a promising biomaterial for wound dressing application.
PMID- 28687394
TI - Umbilical Cord Blood Cytomegalovirus Serostatus Does Not Have an Impact on
Outcomes of Umbilical Cord Blood Transplantation for Acute Leukemia.
AB - Several studies have reported an impact of adult hematopoietic stem cell donor
cytomegalovirus (CMV) serostatus on allogeneic hematopoietic cell transplantation
outcomes. Limited data, however, are available on the impact of cord blood unit
(CBU) CMV serostatus on allogeneic umbilical cord blood transplantation (UCBT)
outcomes. We analyzed, retrospectively, the impact of CBU CMV serostatus on
relapse incidence (RI) and 2-year nonrelapse mortality (NRM) of single-unit CBU
transplantation for acute leukemia. Data from 1177 de novo acute leukemia
pediatric and adult patients transplanted within European Group for Blood and
Marrow Transplantation centers between 2000 and 2012 were analyzed. CBUs were
provided by the European Cord Blood Banks. The median follow-up time for live
patients was 59.9 months. The recipients of CMV-seropositive and -seronegative
CBUs showed a comparable RI (33% versus 35%, respectively, P = .6) and 2-year
cumulative incidence of NRM (31% versus 32%, respectively, P = .5). We conclude
that CBU CMV serostatus did not influence RI and NRM in de novo acute leukemia
patients after allo-UCBT and should not be included as a criteria for cord blood
choice.
PMID- 28687395
TI - Multi-centre audit of VMAT planning and pre-treatment verification.
AB - BACKGROUND AND PURPOSE: We performed a multi-centre intercomparison of VMAT dose
planning and pre-treatment verification. The aims were to analyse the dose plans
in terms of dosimetric quality and deliverability, and to validate whether in
house pre-treatment verification results agreed with those of an external audit.
MATERIALS AND METHODS: The nine participating centres encompassed different
machines, equipment, and methodologies. Two mock cases (prostate and head and
neck) were planned using one and two arcs. A plan quality index was defined to
compare the plans and different complexity indices were calculated to check their
deliverability. We compared gamma index pass rates using the centre's equipment
and methodology to those of an external audit (global 3D gamma, absolute dose
differences, 10% of maximum dose threshold). Log-file analysis was performed to
look for delivery errors. RESULTS: All centres fulfilled the dosimetric goals but
plan quality and delivery complexity were heterogeneous and uncorrelated,
depending on the manufacturer and the planner's methodology. Pre-treatment
verifications results were within tolerance in all cases for gamma 3%-3mm
evaluation. Nevertheless, differences between the external audit and in-house
measurements arose due to different equipment or methodology, especially for 2%
2mm criteria with differences up to 20%. No correlation was found between
complexity indices and verification results amongst centres. CONCLUSIONS: All
plans fulfilled dosimetric constraints, but plan quality and complexity did not
correlate and were strongly dependent on the planner and the vendor. In-house
measurements cannot completely replace external audits for credentialing.
PMID- 28687396
TI - The impact of histology on recurrence patterns in esophageal cancer treated with
definitive chemoradiotherapy.
AB - BACKGROUND: To assess the impact of histology on recurrence patterns and survival
outcomes in patients with esophageal cancer (EC) treated with definitive
chemoradiotherapy (CRT). METHODS: We analyzed 590 consecutive EC patients who
received definitive CRT from 1998 to 2014, including 182 patients (30.8%) with
squamous cell carcinoma (SCC) and 408 (69.2%) with adenocarcinoma. Recurrence
pattern and timing, survival, and potential prognostic factors were compared.
RESULTS: After a median follow-up time of 58.0months, the SCC group demonstrated
a comparable locoregional recurrence rate (42.9% vs. 38.0%, P=0.264) but a
significantly lower distant failure rate (27.5% vs. 48.0%, P<0.001) than
adenocarcinoma group. No significant difference was found in overall survival or
locoregional failure-free survival between groups, whereas the SCC group was
associated with significantly more favorable recurrence-free survival (P=0.009)
and distant metastasis-free survival (P<0.001). The adenocarcinoma group had
higher hematogenous metastasis rates of bone, brain, and liver, whereas the SCC
group had a marginally higher regional recurrence rate. Among patients who
received salvage surgery after locoregional recurrence, no significant difference
in survival was found between groups (P=0.12). CONCLUSIONS: The patterns and
sites of recurrence, survival outcomes, and prognostic factors were significantly
different between esophageal SCC and adenocarcinoma.
PMID- 28687397
TI - ESTRO ACROP consensus guideline on implementation and practice of stereotactic
body radiotherapy for peripherally located early stage non-small cell lung
cancer.
AB - BACKGROUND: Stereotactic body radiotherapy (SBRT) has become the standard of care
for medically inoperable patients with peripherally located, early stage non
small cell lung cancer (NSCLC), and for those refusing surgical resection.
Despite the availability of national and international guidelines, there exists
substantial variability in many aspects of SBRT practice. METHODS: The ESTRO
ACROP guideline is based on a questionnaire covering all aspects of SBRT
implementation and practice (n=114 items). The questionnaire was answered by the
11 faculty members of the ESTRO course "Clinical practice and implementation of
image-guided SBRT" and their 8 institutions. RESULTS: Agreement by >50% of the
institutions was achieved in 72% of all items. Only 8/57 technologies and
techniques were identified as mandatory for SBRT while 32/57 were considered as
optional. In contrast, quality-assurance related elements were considered as
mandatory in 12/24 items. A consensus of risk-adapted SBRT fractionation was
achieved with 3*15Gy for peripherally located lesions and 4*12Gy (PTV D95-D99;
Dmax <125% to <150%) for lesions with broad chest wall contact. For patients free
from severe comorbidities and with favourable long-term OS expectancy, use of the
maximum tolerated dose of 3*18Gy should be considered. CONCLUSIONS: This ACROP
guideline achieved detailed recommendations in all aspects of SBRT implementation
and practice, which will contribute to further standardization of SBRT for
peripherally located early stage NSCLC.
PMID- 28687398
TI - The impact of comorbidities on the benefits of prolonged androgen ablation in
patients with T3-4 prostate cancer treated with external beam radiation therapy.
AB - PURPOSE: To determine whether the survival benefit associated with prolonged
androgen deprivation therapy (ADT) and radiotherapy (EBRT) varies with baseline
estimates of overall survival in cT3-4 prostate cancer patients (PCa). METHODS
AND MATERIALS: In 1997, the BC Cancer Agency adopted as standard a policy of
prolonged ADT (>18months) with EBRT for locally advanced PCa. Two cohorts of cT3
T4 PCa treated with EBRT were selected: 1993-1995 (early: N=725) and 1999-2001
(late: N=584). Duration of ADT and baseline prognostic factors (age, clinical
stage, grade, presenting PSA, and Charlson index (CCI)) were abstracted from
charts. Estimates of 10-year (E10) survival using an age-adjusted CCI were
calculated and patients were grouped into low (<60%), medium (60-90%) and high
(>90%) E10. In each E10 group, actual overall survivals were compared by era
using log rank test. RESULTS: There were 318 low, 544 medium, and 447 high E10
patients with median follow-up of 11.1years. Gleason grade and T stage were not
statistically different between E10 groups. As expected, median age and baseline
CCI were higher in lower E10 groups (p<0.0001). Overall survival was higher in
the late era, but varied with E10 group: low (43% vs. 49%, p=0.54), medium (55%
vs. 64%, p=0.02) and high (66% vs. 77%, p=0.01). CONCLUSION: The policy of
prolonged ADT with EBRT provides a survival benefit that varies with baseline
risk of death from other causes. Absolute benefit from ADT is largest in those
with medium or high E10.
PMID- 28687399
TI - New perspectives for patients with primary CNS lymphoma.
PMID- 28687400
TI - A systems approach to understanding the identification and treatment of sport
related concussion in community rugby union.
AB - AIM: The aim of the present study was to utilise a systems thinking approach to
explore the perceived responsibilities for identifying and treating concussion
held by different actors across the community rugby system (e.g., players,
coaches, parents, medics, referees, and management), as well as their role
specific concussion management strategies. METHODS: A systems approach was taken
to assess what different stakeholders within rugby systems perceive their roles
to be regarding concussion identification and treatment. Through an online
survey, 118 members of the amateur (community) rugby union system were asked
about their role-specific concussion management responsibilities and strategies.
Respondents included players, parents, medics, coaches, club managers,
administrators, and volunteers. RESULTS: The majority of respondents indicated
that they were able to identify the symptoms of rugby-related concussion,
however, only medics stated their responsibility to use formal concussion
assessments (e.g., SCAT2). A smaller number of the respondents indicated that
they were involved in treating concussion within their current role/s (majority
of which were medics). CONCLUSIONS: This study illustrated that the current
challenges in the identification and treatment of rugby-related concussion in
community sport may be due to role/responsibility confusion and possible
overreliance on field-side medics. These findings offer insight into the possible
limitations of the current concussion management guidelines and may offer
empirically based direction for future revisions.
PMID- 28687401
TI - Pathophysiological role of prostaglandin E2-induced up-regulation of the EP2
receptor in motor neuron-like NSC-34 cells and lumbar motor neurons in ALS model
mice.
AB - Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease
characterized by selective degeneration of motor neurons. The primary triggers
for motor neuronal death are still unknown, but inflammation is considered to be
an important factor contributing to the pathophysiology of ALS both clinically
and in ALS models. Prostaglandin E2 (PGE2) and its corresponding four E
prostanoid receptors play a pivotal role in the degeneration of motor neurons in
human and transgenic models of ALS. It has also been shown that PGE2-EP2
signaling in glial cells (astrocytes or microglia) promotes motor neuronal death
in G93A mice. The present study was designed to investigate the levels of
expression of EP receptors in the spinal motor neurons of ALS model mice and to
examine whether PGE2 alters the expression of EP receptors in differentiated NSC
34 cells, a motor neuron-like cell line. Immunohistochemical staining
demonstrated that EP2 and EP3 immunoreactivity was localized in NeuN-positive
large cells showing the typical morphology of motor neurons in mice. Semi
quantitative analysis showed that the immunoreactivity of EP2 in motor neurons
was significantly increased in the early symptomatic stage in ALS model mice. In
contrast, the level of EP3 expression remained constant, irrespective of age. In
differentiated NSC-34 cells, bath application of PGE2 resulted in a concentration
dependent decrease of MTT reduction. Although PGE2 had no effect on cell survival
at concentrations of less than 10 MUM, pretreatment with 10 MUM PGE2
significantly up-regulated EP2 and concomitantly potentiated cell death induced
by 30 MUM PGE2. These results suggest that PGE2 is an important effector for
induction of the EP2 subtype in differentiated NSC-34 cells, and that not only
EP2 up-regulation in glial cells but also EP2 up-regulation in motor neurons
plays a pivotal role in the vulnerability of motor neurons in ALS model mice.
PMID- 28687402
TI - Shift within age-groups of mumps incidence, hospitalizations and severe
complications in a highly vaccinated population. Spain, 1998-2014.
AB - The mumps vaccine (Jeryl-Lynn-strain) was introduced in Spain in 1981, and a
vaccination policy which included a second dose was added in 1995. From 1992
1999, a Rubini-strain based vaccine was administered in many regions but later
withdrawn due to lack of effectiveness. Despite high levels of vaccination
coverage, epidemics have continued to appear. We characterized the three epidemic
waves of mumps between 1998 and 2014, identifying major changes in susceptible
populations using Poisson regression. For the period 1998-2003 (P1), the most
affected group was from 1 to 4years old (y) [Incidence Rate (IR)=71.7
cases/100,000 population]; in the periods 2004-2009 (P2) and 2010-2014 (P3) IR
ratio (IRR) increased among 15-24y (P2=1.46; P3=2.68) and 25-34y (P2=2.17;
P3=4.05). Hospitalization rate (HR), complication rate (CR) and neurological
complication rate (NR) among hospitalized subjects decreased across the
epidemics, except for 25-34y which increased: HR ratio (HRR) (P2=2.18; P3=2.16),
CRR (P3=2.48), NRR (P3=2.41). In Spain mumps incidence increased, while an
overall decrease of hospitalizations and severe complications occurred across the
epidemics. Cohorts born during periods of low vaccination coverage and those
vaccinated with Rubini-strain were the most affected populations, leading to a
shift in mumps cases from children to adolescents and young adults; this also
reveals the waning immunity provided by the mumps vaccine. Despite not preventing
all mumps cases, the vaccine appears to prevent serious forms of the disease.
PMID- 28687404
TI - Significant reduction in notification and seroprevalence rates of hepatitis B
virus infection among the population of Zhejiang Province, China, aged between 1
and 29years from 2006 to 2014.
AB - BACKGROUND AND OBJECTIVE: The Chinese government integrated hepatitis B
vaccination into the national immunization program in 1992, when the hepatitis B
birth dose was introduced in China. Zhejiang province is a relatively developed
area in eastern China and was an area with high endemicity for hepatitis B virus
(HBV) infection via mother-to-child transmission. The hepatitis B vaccine
vaccination rates for the birth dose and 3- dose schedule in Zhejiang Province
since 1992 have both remained above 90% [1]. The results of two hepatitis B
seroepidemiological surveys conducted in 2006 and 2014, respectively, to evaluate
the rates of notification and seroprevalence of HBV infection among the
population of Zhejiang Province, China, aged between 1 and 29years. METHODS: Data
on the notification rates of HBV infection in Zhejiang province from 2006 to 2014
were obtained from the National Notifiable Disease Reporting System (NNDRS). The
prevalence rate of HBV serological markers and the rate of immunization coverage
were compared between surveys. RESULTS: The reported notification rates in people
aged between 1 and 29years according to the NNDRS decreased approximately 4.88
times from 2006 to 2014. The prevalence of HBsAg decreased from 2.16% in 2006 to
1.05% in 2014, while the prevalence of anti-HBc decreased from 7.13% to 5.49%.
The anti-HBc seroprevalence in the 15-29-year-old age group was significantly
higher than that in all the other age groups both in the 2006 and 2014
serosurveys. The rate of anti-HBs seroprevalence in those aged between 1 and
14years was maintained at a high level between 2006 and 2014. CONCLUSIONS: The
rate of hepatitis B reported and the rate of HBsAg positivity decreased
significantly in Zhejiang province by maintaining the high-level coverage rate of
the hepatitis B timely birth dose and three-dose schedule. While additional
efforts are needed to achieve the goal of elimination.
PMID- 28687403
TI - Development of vaccines against Crimean-Congo haemorrhagic fever virus.
AB - Crimean-Congo haemorrhagic fever virus (CCHFV) is a deadly human pathogen of the
utmost seriousness being highly lethal causing devastating disease symptoms that
result in intense and prolonged suffering to those infected. During the past
40years, this virus has repeatedly caused sporadic outbreaks responsible for
relatively low numbers of human casualties, but with an alarming fatality rate of
up to 80% in clinically infected patients. CCHFV is transmitted to humans by
Hyalomma ticks and contact with the blood of viremic livestock, additionally
cases of human-to-human transmission are not uncommon in nosocomial settings. The
incidence of CCHF closely matches the geographical range of permissive ticks,
which are widespread throughout Africa, Asia, the Middle East and Europe. As
such, CCHFV is the most widespread tick-borne virus on earth. It is a concern
that recent data shows the geographic distribution of Hyalomma ticks is
expanding. Migratory birds are also disseminating Hyalomma ticks into more
northerly parts of Europe thus potentially exposing naive human populations to
CCHFV. The virus has been imported into the UK on two occasions in the last five
years with the first fatal case being confirmed in 2012. A licensed vaccine to
CCHF is not available. In this review, we discuss the background and
complications surrounding this limitation and examine the current status and
recent advances in the development of vaccines against CCHFV.
PMID- 28687405
TI - Colonization with 19F and other pneumococcal conjugate vaccine serotypes in
children in St. Louis, Missouri, USA.
AB - BACKGROUND: The epidemiology of nasopharyngeal (NP) pneumococcal carriage varies
with geography and has changed in response to pneumococcal conjugate vaccine
(PCV): a low prevalence (3% or less of colonizing isolates) of colonization by
vaccine-type (VT) pneumococcal serotypes after PCV introduction has been
reported. The primary goal of this study was to determine the VT serotype
prevalence of NP pneumococcal colonization of children residing in the St. Louis,
MO, USA metropolitan area following introduction of the 13-valent PCV in 2010.
The secondary goal of this study was to identify characteristics associated with
NP pneumococcal carriage of any serotype. METHODS: Between July 2013 and April
2016, we enrolled 397 healthy children, aged 0-17years, who required sedation for
procedures or minor surgeries at St. Louis Children's Hospital. NP swabs were
collected after sedation or anesthesia and cultured for pneumococcus. Vaccine
records were obtained from primary care providers or from state immunization
databases. Parents/guardians completed a questionnaire to provide demographics,
past medical history and household characteristics. RESULTS: Of the 88
pneumococcal isolates recovered from 84 colonized subjects (21.2% of all enrolled
subjects; 95% CI 17.2-25.2%), 16 were VT. Eleven isolates were serotype 19F
(12.5%), four (4.5%) were 6A and one (1.1%) was 19A. Prevalence of VT among
colonizing isolates was thus 18.2% (CI 10.1-26.1%) in our cohort, despite
complete PCV vaccination in 87% of colonized children. Factors associated with
pneumococcal colonization by any serotype included younger age and daycare
attendance. CONCLUSION: Children in St. Louis exhibit a higher prevalence of VT
serotypes among pneumococcal carriage isolates than has been reported in other
areas in the US, demonstrating the necessity of ongoing surveillance of local
epidemiology and providing evidence that serotype 19F can remain prevalent in a
pediatric population despite high vaccine uptake.
PMID- 28687406
TI - Comparative efficacy and toxicity of two vaccine candidates against Sporothrix
schenckii using either MontanideTM Pet Gel A or aluminum hydroxide adjuvants in
mice.
AB - Sporotrichosis is an important zoonosis in Brazil and the most frequent
subcutaneous mycosis in Latin America, caused by different Sporothrix species.
Currently, there is no effective vaccine available to prevent this disease. In
this study, the efficacy and toxicity of the adjuvant MontanideTM Pet Gel A (PGA)
formulated with S. schenckii cell wall proteins (ssCWP) was evaluated and
compared with that of aluminum hydroxide (AH). Balb/c mice received two
subcutaneous doses (1st and 14th days) of either the unadjuvanted or adjuvanted
vaccine candidates. On the 21st day, anti-ssCWP antibody levels (ELISA), the
phagocytic index, as well as the ex vivo release of IFN-gamma, IL-4, and IL-17 by
splenocytes and IL-12 by peritoneal macrophages were assessed. Cytotoxicity of
the vaccine formulations was evaluated in vitro and by histopathological analysis
of the inoculation site. Both adjuvanted vaccine formulations increased anti
ssCWP IgG, IgG1, IgG2a, and IgG3 levels, although IgG2a levels were higher in
response to PGA+CWP100, probably contributing to the increase in S. schenckii
yeast phagocytosis by macrophages in the opsonophagocytosis assay when using
serum from PGA+CWP100-immunized mice. Immunization with AH+CWP100 led to a mixed
Th1/Th2/Th17 ex vivo cytokine release profile, while PGA+CWP100 stimulated a
preferential Th1/Th2 profile. Moreover, PGA+CWP100 was less cytotoxic in vitro,
caused less local toxicity and led to a similar reduction in fungal load in the
liver and spleen of S. schenckii- or S. brasiliensis-challenged mice as compared
with AH+CWP100. These results suggest that PGA may be an effective and safe
adjuvant for a future sporotrichosis vaccine.
PMID- 28687408
TI - Development of Postoperative Radiotherapy for Breast Cancer: UK Consensus
Statements - a Model of Patient, Clinical and Commissioner Engagement?
PMID- 28687407
TI - Parents' concerns about vaccine scheduling in Shanghai, China.
AB - BACKGROUND: Several new vaccines have been introduced into China in recent years,
but some parents in China have shown concerns about the scheduling of
vaccinations for young infants. This study explores caregiver concerns about
children receiving multiple vaccines during a single visit and about vaccine
administration in infants <6months, and assesses the degree to which these
concerns are associated with ratings of the importance of different sources of
vaccine information in Shanghai. METHODS: Caregivers of children 8months to
7years presenting at immunization clinics in Shanghai completed a survey about
vaccine co-administration and vaccine administration <6months of age. Respondents
provided ratings of information from different sources (Internet, family/friends,
other parents) and trust in doctors. We analyzed vaccine concerns using linear
regression analyses that included these information sources after adjusting for
socioeconomic variables. RESULTS: Among 618 caregivers, 64% were concerned about
vaccine co-administration and 31% were concerned about vaccine administration to
infants <6months of age. Higher ratings of Internet as an important source of
information were associated with greater concern about co-administration
(beta=0.11, 95% CI: 0.00, 0.22) and concern about administration at <6months of
age (beta=0.17, 95% CI: 0.05, 0.28). Higher ratings given to information from
other parents corresponded to 0.24 points greater concern about vaccine co
administration (95% CI: 0.04, 0.44). More trust in doctors and ratings of
information from friends and family were not associated with vaccine concerns.
CONCLUSIONS: Caregiver concerns about vaccine scheduling may limit China's
flexibility to add vaccines to its official immunization schedule. Reporting
information about vaccine safety on the Internet and bringing groups of parents
together to discuss vaccines might help to ameliorate concerns about vaccine
scheduling.
PMID- 28687409
TI - EphB2 signaling-mediated Sirt3 expression reduces MSC senescence by maintaining
mitochondrial ROS homeostasis.
AB - Disruption of mitochondrial reactive oxygen species (mtROS) homeostasis is a key
factor inducing UCB-MSC senescence. Accordingly, preventing mtROS accumulation
will help in suppressing the UCB-MSC senescence. In this study, we observed that
the expressions of EphrinB2 and EphB2 were inversely regulated by UCB-MSC passage
dependent manner. EphB2 signaling induced mitochondrial translocation of Sirt3.
The knockdown of SIRT3 inhibited the effect of EphB2 signaling in UCB-MSCs.
Subsequently, EphrinB2-Fc induced the nuclear translocation of Nrf-2 via c-Src
phosphorylation dependent manner, and Sirt3 expression was regulated by Nrf-2.
Among Sirt3 target genes, EphB2 signaling increased MnSOD and reduced the mtROS
level in UCB-MSCs. Furthermore, the deacetylase effect of Sirt3 enhanced the
MnSOD activity by deacetylation at the lysine 68 residue and therapeutic effect
of UCB-MSCs on skin-wound healing was increased by EphB2 activation. In
conclusion, the EphB2 can serve as a novel target for the optimizing the
therapeutic use of UCB-MSCs in wound repair by MnSOD-mediated mtROS scavenging
through EphB2/c-Src signaling pathway and Nrf-2-dependent Sirt3 expression.
PMID- 28687410
TI - Radiographic gapometry score: A simple predictor for surgical approach in
pediatric traumatic posterior urethral strictures.
AB - BACKGROUND: Post-traumatic posterior urethral injuries in children are rare
events. Their management algorithms are extrapolations from adult literature and
they continue to pose a difficult challenge for pediatric urologists. Not much
data for age-related feasibility of an end-to-end urethroplasty are available.
OBJECTIVE: This study was designed to validate a simple preoperative radiographic
score to predict the type of surgical repair for traumatic posterior urethral
strictures in children. MATERIALS AND METHODS: This retrospective study was
conducted in a tertiary care center in northern India between 2000 and 2015. All
patients under 15 years with traumatic bulboprostatic stricture disease were
included. Preoperative voiding cystourethrogam (VCUG) and retrograde urethrogram
(RGU) films were used to calculate the gapometry index (G/U index), defined as
the length of urethral gap divided by the bulbar urethral length. This index was
then analyzed for two patient groups based on the anatomical approach employed
for achieving an end-to-end urethroplasty: group 1, who underwent a simple
perineal approach, and group 2, who needed a more elaborate procedure.
Statistical analysis was performed with the two-tailed t-test with SPSS version
18. RESULTS: A total of 38 patients met the inclusion criteria. The age
distribution and G/U index for both groups are detailed in the table. The
difference in mean length of the urethral gap for both groups was statistically
significant (2.1 cm in group 1 vs. 3.6 cm in group 2). There was a direct
correlation between the complexity of surgical procedure required to bridge the
urethral gap and the G/U index. The overall success for urethroplasty in either
group was between 92.3% and 94.6%. DISCUSSION: Urethral extensibility is more
suitable for younger children. This challenges the traditional viewpoint that the
transpubic approach for urethroplasty is more favorable in children. No previous
study has been cited in literature correlating the gapometry index with the
surgical approach for posterior urethral defects. Our results reflect that a
preoperative G/U index of 0.44 correlate with a simple perineal repair, whereas
an index of above 0.87 indicates the likelihood of needing a more elaborate
transpubic approach. CONCLUSIONS: Preoperative assessment of G/U index in
children with traumatic posterior urethral injuries can successfully predict the
operative approach and may therefore aid in better management of these patients.
PMID- 28687411
TI - Systematic review of bladder cancer outcomes in patients with spina bifida.
AB - BACKGROUND: In patients with congenital bladder anomalies, bladder augmentation
is used as a last resort to reduce intravesical pressure, but concerns about
malignant transformation in augmented patients were first raised in the 1980s.
The best evidence to date indicates that augmentation does not appear to increase
the risk of bladder cancer in spina bifida patients. To date, oncologic outcomes
from patients with spina bifida with and without augmentation have only been
available in small case reports. OBJECTIVE: To systematically evaluate factors in
myelomeningocele patients with bladder cancer, including bladder augmentation,
that contribute to overall survival (OS). STUDY DESIGN: A systematic review using
PubMed was conducted by cross referencing terms 'myelomeningocele,'
'cystoplasty,' 'bladder cancer' and respective synonyms according to the
Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)
statement. Inclusion criteria were studies with patients with an underlying
diagnosis of myelomeningocele and bladder cancer with data on age, stage, and
mortality status. Studies were excluded for spinal cord injury, history of
tuberculosis or schistosomiasis, or prior ureterosigmoidostomy. RESULTS: Fifty
two patients were identified from 28 studies with a median age at bladder cancer
diagnosis of 41 years (range 13-73); 37 (71%) presented with stage III or IV
bladder cancer. Overall survival at 1 year and 2 years was 48.5% and 31.5%,
respectively. Overall survival was different between those with and without
augmentation (P = 0.009) by log-rank analysis. No between-group differences in OS
were seen based on age, management with indwelling catheter, diversion with ileal
conduit or being on a surveillance program. Only stage remained a significant
predictor of OS on multivariate analysis (HR 2.011, 95% CI 1.063-3.804, P =
0.032). Secondary analysis was performed after removing patients with gastric
augmentation (n = 8), and no difference in OS was seen between patients with (n =
8) and without augmentation (n = 36, P = 0.112). Of augmented patients, latency
to development of bladder cancer was variable (Summary Figure). DISCUSSION:
Bladder cancer is a deadly diagnosis in patients with congenital bladder
anomalies like spina bifida, and while overall prevalence of the two conditions
occurring together is low, bladder cancer will go on to affect 2-4% of spina
bifida patients. The present study examined overall survival, and further
characterized outcomes in these patients. Presence of a bladder augment did not
appear to worsen overall survival. CONCLUSIONS: Patients with myelomeningocele
who developed bladder cancer had aggressive disease. Augmentation did not worsen
OS, based on cases reported in the literature. Risk of bladder cancer should be
discussed with all myelomeningocele patients.
PMID- 28687412
TI - Azithromycin in uncontrolled asthma.
PMID- 28687413
TI - Effect of azithromycin on asthma exacerbations and quality of life in adults with
persistent uncontrolled asthma (AMAZES): a randomised, double-blind, placebo
controlled trial.
AB - BACKGROUND: Exacerbations of asthma cause a substantial global illness burden.
Adults with uncontrolled persistent asthma despite maintenance treatment require
additional therapy. Since macrolide antibiotics can be used to treat persistent
asthma, we aimed to assess the efficacy and safety of oral azithromycin as add-on
therapy in patients with uncontrolled persistent asthma on medium-to-high dose
inhaled corticosteroids plus a long-acting bronchodilator. METHODS: We did a
randomised, double-blind, placebo controlled parallel group trial to determine
whether oral azithromycin decreases the frequency of asthma exacerbations in
adults (>=18 years) with symptomatic asthma despite current use of inhaled
corticosteroid and long-acting bronchodilator, and who had no hearing impairment
or abnormal prolongation of the corrected QT interval. Patients were randomly
assigned (1:1) to receive azithromycin 500 mg or placebo three times per week for
48 weeks. Patients were centrally allocated using concealed random allocation
from a computer-generated random numbers table with permuted blocks of 4 or 6 and
stratification for centre and past smoking. Primary efficacy endpoints were the
rate of total (severe and moderate) asthma exacerbations over 48 weeks and asthma
quality of life. Data were analysed on an intention-to-treat basis. The trial is
registered at the Australian and New Zealand Clinical Trials Registry (ANZCTR),
number 12609000197235. FINDINGS: Between June 12, 2009, and Jan 31, 2015, 420
patients were randomly assigned (213 in the azithromycin group and 207 in the
placebo group). Azithromycin reduced asthma exacerbations (1.07 per patient-year
[95% CI 0.85-1.29]) compared with placebo (1.86 per patient-year [1.54-2.18];
incidence rate ratio [IRR] 0.59 [95% CI 0.47-0.74]; p<0.0001). The proportion of
patients experiencing at least one asthma exacerbation was reduced by
azithromycin treatment (127 [61%] patients in the placebo group vs 94 [44%]
patients in the azithromycin group, p<0.0001). Azithromycin significantly
improved asthma-related quality of life (adjusted mean difference, 0.36 [95% CI
0.21-0.52]; p=0.001). Diarrhoea was more common in azithromycin-treated patients
(72 [34%] vs 39 [19%]; p=0.001). INTERPRETATION: Adults with persistent
symptomatic asthma experience fewer asthma exacerbations and improved quality of
life when treated with oral azithromycin for 48 weeks. Azithromycin might be a
useful add-on therapy in persistent asthma. FUNDING: National Health and Medical
Research Council of Australia, John Hunter Hospital Charitable Trust.
PMID- 28687414
TI - Ovarian expression and localization of clathrin (Cltc) components in cutthroat
trout, Oncorhynchus clarki: Evidence for Cltc involvement in endocytosis of
vitellogenin during oocyte growth.
AB - To evaluate potential involvement of clathrin in endocytosis of vitellogenin
(Vtg) by teleost oocytes, cDNAs encoding clathrin heavy chain (cltc) were cloned
from ovaries of cutthroat trout. Quantitative PCR revealed three types of cltc
(cltc-a1, cltc-a2, cltc-b) to be expressed in 10 different tissues including the
ovary. The cltc-a1 alone exhibited a significant decrease in ovarian expression
during vitellogenesis; this was correlated with a corresponding decrease in
transcripts encoding the major Vtg receptor (Vtgr). No development-related
changes in ovarian cltc-a2 or cltc-b transcript levels were observed. In situ
hybridization revealed a strong ctlc signal in pre-vitellogenic oocytes, but not
in vitellogenic oocytes. Western blotting using a rabbit antiserum (a-Cltc)
raised against a recombinant Cltc preparation detected a polypeptide band with an
apparent mass of ~170kDa in vitellogenic ovary extracts. Immunohistochemistry
using a-Cltc revealed Cltc to be uniformly distributed throughout the ooplasm of
perinucleolus stage oocytes, translocated to the periphery of lipid droplet stage
oocytes, and localized to the oolemma during vitellogenesis. These patterns of
cltc/Cltc distribution and abundance during oogenesis, which are identical to
those previously reported for vtgr/Vtgr in this species, constitute the first
empirical evidence that cltc-a1/Cltc-a1 is involved in Vtg endocytosis via the
Vtgr in teleost fish.
PMID- 28687415
TI - Age-related changes in the morphological relationship between the supratubal
recess and the Eustachian tube.
AB - OBJECTIVE: To study age-related changes in the morphology of the supratubal
recess (STR) and its relationship with the Eustachian tube (ET). METHODS: Seventy
randomly selected computed tomography (CT) images of non-pathological temporal
bones of 49 patients were reviewed retrospectively. The patients were grouped
according to age into 4 age groups: group A (0-3 years), group B (4-8 years),
group C (9-18 years) and group D (19-50 years). Space analytic geometry was
assessed to directly calculate the morphology of the STR and the ET. RESULTS: In
normal temporal bones, the STR was mostly presented with a solitary cell in life.
The length of the STR was significantly longer in group C than that in group A
(P<0.05). The width of the STR was declined with age and presented with
significant difference among age groups (P<0.05). No significant difference was
observed in the height of the STR in whole age groups (P>0.05). The aeration of
the STR was intimately related with age-related morphological changes in the ET.
But the important factors influencing the aeration of the STR were not always the
same in different age stages. CONCLUSION: The extended length and declined width
of the STR with age were mostly related with the prolonging bony part and
inwardly bending cartilaginous part of the ET in children and adolescent aged
from 0 to 18 years old. In adults aged more than 18 years old, the narrowed
caliber of the tympanic orifice of the ET could induce the decline in the width
of the STR with age, but unfolded horizontal cartilaginous part of the ET
contributed to stable length and height in aeration of the STR.
PMID- 28687416
TI - The effect of interaction of heat and UVB on human keratinocyte: Novel insights
on UVB-induced carcinogenesis of the skin.
AB - BACKGROUND: Skin cancer is an important environmentally-related health issue.
Although sun exposure is closely associated with increasing environmental heat,
the effects of environmental heat on the skin, especially in the context of
photocarcinogenesis, has not been carefully examined. OBJECTIVES: This study
aimed to explore the effects and interactions of UVB radiation and environmental
heat on photocarcinogenesis of the skin using cell and animal models. METHODS:
Cultured keratinocytes and hairless mice were exposed to different treatment
conditions including UVB radiation and environmental heat. The effects of
treatment on keratinocyte and mice skin were evaluated at indicated time points.
RESULTS: UVB induced DNA damage was significantly lower in keratinocytes that
were pretreated in an environment with slightly elevated temperature followed by
UVB treatment (Heat-UVB) as compared to UVB and UVB radiation followed by
exposure to equivalent increase in environmental heat (UVB-Heat) groups. Similar
phenomenon was observed in terms of keratinocyte viability. In the animal model,
it was found that Heat-UVB treated mice showed delayed and reduced tumor
formation as compared to the UVB and UVB-Heat treated groups. Quantum simulation
analyses demonstrated that the energy required for CPD formation at environment
with higher temperature required considerable higher energy as compared to CPD
formation at lower temperature. CONCLUSION: Taken together, our results
demonstrated that with equivalent UVB exposure, higher temperature environment
may protect cells against subsequent UVB-induced DNA damages.
PMID- 28687417
TI - Just a minute meditation: Rapid voluntary conscious state shifts in long term
meditators.
AB - Meditation induces a modified state of consciousness that remains under voluntary
control. Can meditators rapidly and reversibly bring about mental state changes
on demand? To check, we carried out 128 channel EEG recordings on Brahma Kumaris
Rajayoga meditators (36 long term: median 14240h meditation; 25 short term:
1095h) and controls (25) while they tried to switch every minute between rest and
meditation states in different conditions (eyes open and closed; before and after
an engaging task). Long term meditators robustly shifted states with enhanced
theta power (4-8Hz) during meditation. Short term meditators had limited ability
to shift between states and showed increased lower alpha power (8-10Hz) during
eyes closed meditation only when pre and post task data were combined. Controls
could not shift states. Thus trained beginners can reliably meditate but it takes
long term practice to exercise more refined control over meditative states.
PMID- 28687418
TI - Expectation creates something out of nothing: The role of attention in iconic
memory reconsidered.
AB - Conscious experience is modulated by attention and expectation, yet is believed
to be independent of attention. The experiments on iconic memory (IM) are usually
taken as support for this claim. However, a recent experiment demonstrated that
when attention is diverted away from the IM letter display subjects fail to see
the absence of IM letters. Here we contribute to the ongoing debate by overcoming
experimental shortcomings of this previous experiment, by measuring subjective
visibility and by testing the effect of the post-cue. We were able to replicate
these earlier findings and extend them by demonstrating that subjects who do not
realize the absence of letters perceive illusory letters. This result means that
there is still phenomenal consciousness, even when attention is diverted.
Expectation creates illusory content that overwrites valid IM content. Taken
together these findings suggest that the present experimental paradigm is not
appropriate to make claims about IM content.
PMID- 28687419
TI - Selective liver toxicity and therapeutic progress in acute lymphoblastic
leukaemia.
PMID- 28687420
TI - Hepatic adverse event profile of inotuzumab ozogamicin in adult patients with
relapsed or refractory acute lymphoblastic leukaemia: results from the open
label, randomised, phase 3 INO-VATE study.
AB - BACKGROUND: The INO-VATE study demonstrated efficacy and safety of inotuzumab
ozogamicin versus standard care in adults with relapsed or refractory B-cell
acute lymphoblastic leukaemia. Here, we report the frequency of, and potential
risk factors for, hepatotoxicity in patients in this trial and after treatment
and subsequent haemopoietic stem-cell transplantation (HSCT). METHODS: In this
open-label, phase 3, multicentre, international study, adults with relapsed or
refractory, CD22-positive, Philadelphia chromosome (Ph)-positive or Ph-negative B
cell acute lymphoblastic leukaemia who were due to receive first or second
salvage treatment were randomly assigned (1:1) via an interactive voice response
system to receive inotuzumab ozogamicin (starting dose 1.8 mg/m2 per cycle [0.8
mg/m2 on day 1; 0.5 mg/m2 on days 8 and 15 of a 21-28 day cycle for <=6 cycles])
or standard care (either fludarabine plus cytarabine plus granulocyte colony
stimulating factor, mitoxantrone plus cytarabine, or high-dose cytarabine).
Stratification factors at randomisation were duration of first remission (<12
months vs >=12 months), salvage treatment phase (first vs second), and age (<55
years vs >=55 years). We present data up to March 8, 2016. At this cutoff date,
all patients had been discontinued from treatment but 54 patients were continuing
in long-term follow-up. Long-term follow-up has now been completed, with the
final patient's last visit on Jan 4, 2017. This prespecified safety analysis
describes investigator-assessed treatment-emergent hepatotoxicity, including
sinusoidal obstruction syndrome (also known as veno-occlusive disease) in
patients during study treatment or thereafter (without follow-up HSCT) and after
study treatment and subsequent HSCT, for all patients who received at least one
dose of study treatment. This study is registered with ClinicalTrials.gov, number
NCT01564784. FINDINGS: Between Aug 27, 2012, and and the data cutoff of March 8,
2016, 326 patients were randomly assigned to receive inotuzumab ozogamicin
(n=164) or standard care (n=162). 164 patients in the inotuzumab ozogamicin group
and 143 in the standard care group received at least one dose of study treatment
and were included in the safety population. At data cutoff, median duration of
treatment (induction) was 8.9 weeks (IQR 4.1-13.1) in the inotuzumab ozogamicin
group and 0.9 weeks (0.9-1.1) in the standard care group. Treatment-emergent
hepatotoxicities (of all grades) were more frequent in the inotuzumab ozogamicin
group (83 [51%] of 164 patients) than in the standard care group (49 [34%] of 143
patients). The frequency of sinusoidal obstruction syndrome-comprising events
occurring during treatment (or follow-up without HSCT) and after treatment and
subsequent HSCT-was higher in the inotuzumab ozogamicin group (22 [13%]; 18 [82%]
of which were grade 3 or worse) than in the standard care group (one [<1%]).
During study therapy or follow-up without HSCT, five (3%) patients in the
inotuzumab ozogamicin group developed sinusoidal obstruction syndrome compared
with no patients in the standard care group. Of the 77 patients who received
inotuzumab ozogamicin and proceeded to HSCT, 17 (22%) had sinusoidal obstruction
syndrome; five events after follow-up HSCT were fatal. Of 32 patients who
received standard care and proceeded to HSCT, one (3%) had (non-fatal) sinusoidal
obstruction syndrome that was ongoing at the time of death due to septic shock.
In multivariate analysis, conditioning with two alkylating agents (p=0.015 vs one
alkylating agent) and last available pre-HSCT bilirubin concentration of greater
than or equal to the upper limit of normal (ULN; p=0.009 vs =20 mm
compared with those <20 mm. METHODS: A retrospective analysis was performed of
patients treated by EVAR at the study institution between 2006 and 2012,
including patients with available information about the type of iliac stent
grafts and a minimum follow-up (FU) of 3 years with contrast enhanced CT, or
those that had developed a type 1b endoleak earlier. The cohort was divided into
two groups: Group I included iliac limbs with a distal diameter <20 mm, and Group
II included all iliac limbs with a distal diameter >=20 mm. RESULTS: Of 692 limbs
(346 patients), 239 limbs (34.5%) from 129 patients were included in the
analysis. Mean CT FU was 53 months, 178 had an iliac stent graft diameter <20 mm
(Group I), and 61 a diameter of >=20 mm (Group II). Mean oversizing for iliac
limbs was 17.2% (IQR 14) and there was no case of immediate type 1b endoleak. For
the whole group, 18 type 1b endoleaks occurred during FU (7.5%) after a mean of
37.7 months (range 4-96). Eleven of 61 (18%) iliac limbs in Group II developed a
type 1b endoleak during FU in contrast to 7/178 (3.9%) in Group I (OR 5.3, 95% CI
1.98-14.59, p = 0,001). The ROC curve analysis indicated a limb diameter of 19 mm
as a cutoff value for a higher probability of developing a type 1b endoleak.
CONCLUSION: Patients treated with iliac limbs >=20 mm had a fivefold higher risk
of late (mean 37 months) type 1b endoleak compared with patients treated with a
distal iliac limb diameter <20 mm.
PMID- 28687429
TI - Ecological effects of scrubber water discharge on coastal plankton: Potential
synergistic effects of contaminants reduce survival and feeding of the copepod
Acartia tonsa.
AB - To meet the oncoming requirements for lower sulphur emissions, shipping companies
can install scrubbers where the exhaust is sprayed with seawater and subsequently
discharged to the sea. The discharge water has a pH around 3 and contains
elevated concentrations of vanadium, nickel, lead and hydrocarbons. We
investigated 1) the threshold concentrations of scrubber discharge water for
survival, feeding and reproduction of the copepod Acartia tonsa, 2) whether the
effects depend on the exposure route and 3) whether exposure to discharge water
can be detected in field-collected organisms. A direct exposure to discharge
water increased adult copepod mortality and reduced feeding at metal
concentrations which were orders of magnitude lower than the lethal
concentrations in previous single-metal studies. In contrast, reproduction was
not influenced by dietary uptake of contaminants. Scrubber water constituents
could have synergistic effects on plankton productivity and bioaccumulation of
metals, although the effects will depend on their dilution in the marine
environment.
PMID- 28687430
TI - Management of the lateral neck in well differentiated thyroid cancer.
AB - Lateral neck lymph node metastases in well differentiated thyroid cancer are
common, ranging from 30% to 60%, with the majority of these foci identifiable
only as microscopic deposits. A skilled ultrasound evaluation of the lymph nodes
in the lateral neck is recommended for all patients presenting with newly
diagnosed thyroid cancer undergoing surgical management. Ultrasound guided fine
needle aspiration biopsy may be used to cytologically confirm suspected lateral
neck nodal metastases prior to surgery. For patients with large volume nodal
disease, extranodal extension, or multiple nodal metastases, computed tomography
(CT) scan of the neck with contrast is an important additional imaging modality
to accurately localize disease prior to surgery. Primary surgical management for
lateral neck disease typically includes lateral neck dissection in conjunction
with total thyroidectomy. Postoperative adjuvant radioactive iodine is typically
recommended for patients with clinically evident nodal metastases, or for those
with over 5 micrometastatic nodes. In the recurrent or persisting disease
setting, complete surgical resection of local and regional disease remains the
main treatment approach. However, sub-centimeter nodal disease may take an
indolent course, and active surveillance may be a reasonable approach in selected
clinical circumstances. Conversely, external beam radiation therapy (EBRT) may be
considered for scenarios with unresectable disease, or microscopic residual
disease following surgery in a clinically unfavorable setting. Two multi-kinase
inhibitors (sorafenib and lenvatinib) are now FDA approved for treatment of RAI
refractory thyroid cancer and now play an important role in the management of
progressive, metastatic and surgically incurable disease.
PMID- 28687431
TI - Resectable invasive IPMN versus sporadic pancreatic adenocarcinoma of the head of
the pancreas: Should these two different diseases receive the same treatment? A
matched comparison study of the French Surgical Association (AFC).
AB - PURPOSE: To compare survival and impact of adjuvant chemotherapy in patients who
underwent pancreaticoduodenectomy (PD) for invasive intraductal papillary
mucinous neoplasm (IIPMN) and sporadic pancreatic ductal adenocarcinoma (PDAC).
METHODS: From 2005 to 2012, 240 patients underwent pancreatectomy for IIPMN and
1327 for PDAC. Exclusion criteria included neoadjuvant treatment, pancreatic
resection other than PD, vascular resection, carcinoma in situ, or <11 examined
lymph nodes. Thus, 82 IIPMN and 506 PDAC were eligible for the present study.
Finally, The IIPMN group was matched 1:2 to compose the PDAC group according to
TNM disease stage, perineural invasion, lymph node ratio, and margin status.
RESULTS: There was no difference in patient's characteristics, intraoperative
parameters, postoperative outcomes, and histologic parameters. Overall survival
and disease-free survival times were comparable between the 2 groups. In each
group, overall survival time was significantly poorer in patients who did not
achieve adjuvant chemotherapy (p = 0.03 for the IIPMN group; p = 0.03 for the
PDAC group). In lymph-node negative patients of the IIPMN group, adjuvant
chemotherapy did not have any significant impact on overall survival time (OR =
0.57; 95% CI [0.24-1.33]). Considering the whole population (i.e. patients with
IIPMN and PDAC; n = 246), patients who did not achieve adjuvant chemotherapy had
poorer survival (p < 0.01). CONCLUSIONS: The courses of IIPMN and PDAC were
similar after an optimized stage-to-stage comparison. Adjuvant chemotherapy was
efficient in both groups. However, in lymph node negative patients, adjuvant
chemotherapy seemed not to have a significant impact.
PMID- 28687432
TI - Nonsteroidal anti-inflammatory drugs and the risk of anastomotic leakage after
anterior resection for rectal cancer.
AB - BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) have been widely used
in colorectal surgery due to their opioid-sparing effect. However, several
studies have indicated an increased risk of anastomotic leakage following NSAID
treatment, although conflicting results exist. The primary goal of this study was
to further examine whether postoperative NSAIDs are independently associated with
anastomotic leakage after anterior resection for rectal cancer. METHODS: Patients
who underwent anterior resection for rectal cancer during 2007-2013 in 15
different hospitals in three healthcare regions in Sweden were included in the
study. Registry data and information from patient records were retrieved. The
association between NSAID treatment (for at least two days in the first
postoperative week) and symptomatic anastomotic leakage (within 90 days) was
evaluated with multiple logistic regression, with adjustment for pertinent
confounding factors. RESULTS: Some 1495 patients were included in the study. Of
these, 27% received postoperative NSAIDs for at least two days in the first
postoperative week. Symptomatic anastomotic leakage occurred in 11% and 14% in
the NSAID and non-NSAID group, respectively. With adjustment for confounders, the
odds ratio for leakage among patients who received NSAIDs compared with those who
did not was 0.88 (95% CI 0.65-1.20). No differences were seen between non
selective and COX-2-selective NSAIDs. CONCLUSION: Postoperative NSAID treatment
does not seem to increase the risk of symptomatic anastomotic leakage after
anterior resection for rectal cancer. NSAID use appears to be safe, but a well
powered randomized clinical trial is warranted.
PMID- 28687433
TI - Responsibility and compassion in prehospital support to survivors of suicide
victim - Professionals' experiences.
PMID- 28687434
TI - Prevalence of Barrett's esophagus: An observational study from a gastroenterology
clinic.
AB - INTRODUCTION AND AIMS: Barrett's esophagus is a condition that predisposes to
esophageal adenocarcinoma. Our aim was to establish the prevalence of Barrett's
esophagus at our center, as well as determine its associated factors. MATERIALS
AND METHODS: We retrospectively assessed the endoscopic reports of 500
outpatients seen at our Gastroenterology Service from November 2014 to April
2016. We determined the prevalence of Barrett's esophagus and analyzed the
demographic, clinical, and endoscopic findings associated with that pathology.
RESULTS: The prevalence of Barrett's esophagus was 1.8%. The mean age of the
patients with Barrett's esophagus was 58.7 years (range: 45-70) and there was a
predominance of men (66%). In the subgroup of patients with symptoms of
gastroesophageal reflux (n=125), Barrett's esophagus prevalence was 7.2%. In the
multivariate analysis, the factors that were independently associated with
Barrett's esophagus were gastroesophageal reflux (P=.005) and hiatal hernia
(P=.006). CONCLUSIONS: The overall prevalence of Barrett's esophagus was 1.8% in
our population, with a prevalence of 7.2% in patients that had symptoms of
gastroesophageal reflux.
PMID- 28687435
TI - Evaluation of coexisting polymyositis in feline myasthenia gravis: A case series.
AB - Acquired myasthenia gravis (MG) is relatively uncommon in cats. In humans, MG may
be associated with other immune-mediated disorders, in particular polymyositis
(PM). In this study, we described in-depth electrodiagnostic findings and
pathological changes in muscles of cats diagnosed with MG, and assessed the
presence of concurrent PM. Six cats with confirmed acetylcholine receptor
antibody seropositive MG, and two suspected cases with clinical signs and
electrophysiological changes consistent with MG, were reviewed. All animals
presented with severe typical signs of generalized weakness and/or fatigability,
resembling late-onset MG in humans, in addition to regurgitation. Five cats
presented a cranial mediastinal mass, with 3 confirmed as thymoma. Repetitive
nerve stimulation revealed a decrement of the compound muscle action potential in
all tested cases, starting from low frequencies of stimulation. Serum creatine
kinase activity was increased in 6/8 cats. Muscle biopsies performed in 5 cats
revealed varying degrees of mixed mononuclear cell infiltrates, positive for the
leukocyte markers CD3/CD4/CD8 and CD11b. Further MHC-1/C5b-9 positive sarcolemmal
deposits were identified in all tested cases, with or without thymoma. This study
documents an association of MG and PM in cats, and provides further support for
feline MG as a relevant animal model of human MG.
PMID- 28687436
TI - A novel fully automated system for quantification of Hepatitis B virus DNA using
magnetic bead-based method combined with real-time PCR.
AB - BACKGROUND: Hepatitis B virus (HBV) infection is a major global health problem
and causes liver damage as cirrhosis of the liver or liver cancer. Development of
an accurate, sensitive and reproducible detection method for detecting and
monitoring HBV DNA is very necessary and urgent. OBJECTIVES: The aims were to
evaluate the analytical performances of the fully automated Pre-NAT system
comparing to domestic assay, and to explore the role of highly sensitive
quantification of HBV DNA in the management of chronic HBV infection. STUDY
DESIGN: Pseudo-viral particles at high HBV DNA concentration were serially
diluted to assess linear range. Accuracy and lower limit of detection were
assessed by determining a panel of HBV standard substance. HBV DNA positive
clinical specimen and internal quality control were measured 20 times to evaluate
precision and reproducibility. 20 non HBV-infected specimens were used for the
specificity assay. 96 chronic hepatitis B samples were quantified for HBV DNA to
evaluating the correlation between the new test and Da-an assay. HBV serological
markers were detected using ELISA method. RESULTS: Pre-NAT quantitated HBV DNA
levels covered a wide dynamic range (10 logs) with a close correlation between
expected and observed values (r=0.999, P<0.05), satisfactory precision and higher
specificity. The lower detection limit was 20IU/mL. Comparability assay showed
Pre-NAT had a good agreement with but more sensitive than Da-an assay (t=0.149,
P>0.05). HBV DNA level was partially correlated to but more reliable and
sensitive than serological evidence in reflecting the viral level. CONCLUSION:
This novel fully-automated real-time PCR assay exhibits good analytical and
clinical performances for highly sensitive detection of HBV DNA. It is well
suited for monitoring antiviral responses and making treatment strategies
according to current clinical practice guidelines for the management of chronic
HBV infection.
PMID- 28687437
TI - Brain projective reality: Novel clothes for the emperor: Reply to comments on
"Topodynamics of metastable brains" by Arturo Tozzi et al.
PMID- 28687438
TI - One-session "2-step" technique for endoscopic full-thickness resection of a large
rectal adenocarcinoma: when it is possible, overcome the lesion's size.
PMID- 28687439
TI - Subsquamous intestinal metaplasia is common in treatment-naive Barrett's
esophagus.
AB - BACKGROUND AND AIMS: Barrett's intestinal metaplasia may extend beneath normal
squamous epithelium at the squamocolumnar junction (SCJ) and therefore escape
surveillance biopsy sampling. The prevalence of subsquamous intestinal metaplasia
(SSIM) in patients undergoing Barrett's esophagus (BE) surveillance is unknown.
Our aim was to examine the prevalence and distribution of SSIM proximal to the
SCJ in patients undergoing BE surveillance. METHODS: We enrolled consecutive
patients with biopsy specimen-proven BE. Biopsy specimens were obtained from the
squamous epithelium at 5 mm and 10 mm above the SCJ. The primary outcomes were
the proportion of patients with SSIM at each level. We further assessed factors
associated with SSIM. RESULTS: We examined 515 squamous epithelial biopsy
specimens from 106 BE patients (95% men; mean age, 66 years) with a mean
Barrett's length of 3.0 cm. SSIM was present in 39% at 5 mm (95% CI, 29.4-48.6)
and 21% (95% CI, 11.7-32.1) at 10 mm proximal to the SCJ. Among all biopsy
specimens, 13% (95% CI, 10.6-16.6) contained SSIM: 17% (95% CI, 13-21.6) of
biopsy samples at 5 mm and 8% (95% CI, 4.3-12.2) at 10 mm proximal to the SCJ.
SSIM was more common in the anterior/right lateral position compared with the
posterior/left lateral position (21% vs 11%, P = .001). None of the biopsy
specimens showed dysplasia. Length of BE or duration of reflux symptoms were not
associated with the presence of SSIM. CONCLUSIONS: This cross-sectional study
found a surprisingly high proportion of SSIM in treatment-naive patients proximal
to the SCJ. These findings raise questions regarding BE management and the
prevalence of SSIM in normal-appearing esophagus.
PMID- 28687440
TI - Variation in Coverage for Progesterone to Prevent Preterm Birth: A Survey of
Medicaid Managed Care Organizations.
AB - INTRODUCTION: Preterm birth is the leading cause of U.S. infant morbidity and
mortality; Medicaid enrollees disproportionately experience preterm deliveries.
Data suggest that progesterone-an evidence-based therapy for preventing preterm
birth-is not accessible to all eligible Medicaid beneficiaries. This study aimed
to identify variation in progesterone coverage guidelines in a sample of state
Medicaid managed care organizations (MMCOs). MATERIAL AND METHODS: Using a cross
sectional design, participation in a web-based survey was offered to 20 MMCO
members of the Medicaid Health Plans of America. The survey assessed coverage
guidelines for progesterone and associated interventions to prevent preterm
birth. MMCOs identified key barriers in providing progesterone. Descriptive
analyses were performed. RESULTS: Analyses included data from 18 plans providing
coverage in 31 of the 39 states with MMCOs (response rate, 90.0%). Responding
MMCOs were diverse: 55.6% were multistate, 33.3% were nonprofit, and 31.2%
covered more than 1,000,000 lives. Most respondents (87.5%) covered branded
progesterone, and 81.3% covered compounded progesterone. Prior authorization was
required by most plans for branded progesterone (86.7%) or compounded
progesterone (75.0%). The MMCO gestational age restrictions for initiating
progesterone varied from 22 to 37 weeks of gestation, even within the same state.
MMCO-identified barriers to providing progesterone included cost, lack of
clinician knowledge of indications and coverage, and variation in billing
procedures. DISCUSSION: Marked variation in MMCO coverage policies and procedures
for progesterone and related interventions to prevent preterm birth was noted.
IMPLICATIONS FOR PRACTICE AND POLICY: Standardizing MMCO coverage policies may be
one way to improve access to evidence-based interventions that prevent preterm
birth.
PMID- 28687442
TI - Increased BACE1 activity inhibits peripheral nerve regeneration after injury.
AB - Axons of the peripheral nervous system possess the capacity to regenerate
following injury. Previously, we showed that genetically knocking out Beta-Site
APP-Cleaving Enzyme 1 (BACE1) leads to increased nerve regeneration. Two cellular
components, macrophages and neurons, contribute to enhanced nerve regeneration in
BACE1 knockout mice. Here, we utilized a transgenic mouse model that
overexpresses BACE1 in its neurons to investigate whether neuronal BACE1 has an
inverse effect on regeneration following nerve injury. We performed a sciatic
nerve crush in BACE1 transgenic mice and control wild-type littermates, and
evaluated the extent of both morphological and physiological improvements over
time. At the earliest time point of 3days, we observed a significant decrease in
the length of axonal sprouts growing out from the crush site in BACE1 transgenic
mice. At later times (10 and 15days post-crush), there were significant
reductions in the number of myelinated axons in the sciatic nerve and the
percentage of re-innervated neuromuscular junctions in the gastrocnemius muscle.
Transgenic mice had a functional electrophysiological delay in the recovery up to
8weeks post-crush compared to controls. These results indicate that BACE1
activity levels have an inverse effect on peripheral nerve repair after injury.
The results obtained in this study provide evidence that neuronal BACE1 activity
levels impact peripheral nerve regeneration. This data has clinical relevance by
highlighting a novel drug target to enhance peripheral nerve repair, an area
which currently does not have any approved therapeutics.
PMID- 28687443
TI - Ganglioglioma of brain stem and cervicomedullary junction: A 50years review of
literature.
AB - Gangliogliomas are rare low-grade brain tumors composed of both neoplastic glial
and neuronal cell elements. The treatment modalities are relatively different in
this location and hence factors affecting outcome are poorly understood. We
identified 142 brain stem GG patients across 46 studies. The average age was
11.4years with significant difference b/w males and females under the age of 20
(p=0.001). 100% of tumors in the CMJ while, 72% of type I and 86% of type II
tumors demonstrated contrast enhancement. 72% of type I and 86% of type II tumors
demonstrated contrast enhancement. All BRAF mutation positive tumors demonstrated
contrast enhancement. Medulla and pons was the most favorable location followed
by medulla alone, and the CMJ. In all tumors "gross total resection" (GTR, 16%),
"subtotal resection" (STR, 48%) or "partial resection" (PR, 36%) was achieved.
Most subtypes II and III were partially resected (86% and 66%), while, subtype I
underwent STR (66%). Only 55% of the patients were positive for the BRAF V600E
mutation. The overall survival dropped from 50% at 24 to 10% at 60months,
postoperatively. Through this review, we found that an early diagnosis, location,
and with the imaging characteristics are vital part of the preoperative planning.
Surgical resection is highly dependent on location in the brain stem with radical
resection only limited to the most contrast enhancing portion of these tumors.
BRAF V600E mutation status should be considered to allow the possibility of
targeted therapy in case of a residual tumor and/or regrowth.
PMID- 28687441
TI - De-escalation of treatment in HER2-positive breast cancer: Determinants of
response and mechanisms of resistance.
AB - Overexpression and/or gene amplification of HER2, a crucial member of the HER
family of four receptors, occur in about 15-20% of breast cancers and define an
aggressive subtype of the disease. Activated HER homo and heterodimers govern a
complex and redundant downstream signaling network that regulates cell survival
and metastasis. Despite treatment with effective HER2-targeted therapies, many
HER2-positive tumors fail to respond, or initially respond but eventually develop
resistance. One of the upfront reasons for this treatment failure is failure to
accurately select the tumors that are truly dependent on HER2 for survival and so
would benefit the most from HER2-targeted therapy. In these truly HER2-addicted
tumors (i.e. physiologically dependent), resistance could be the result of an
incomplete inhibition of signaling at the HER receptor layer. In this regard,
preclinical and clinical studies have documented the superiority of combination
anti-HER2 therapy over single agent therapy to achieve a more comprehensive
inhibition of the various HER receptor dimers. HER2 can be further activated or
reactivated by mutations or other alterations in HER2 itself, or in other HER
family members. Even when a complete and sustained HER inhibition is achieved,
resistance to anti-HER therapy can arise by other somewhat dominant mechanisms,
including preexisting or emerging alternative signaling pathways such as the
estrogen receptor, deregulated downstream signaling components, especially of the
PI3K pathway, and the tumor immune microenvironment. Most of the clinical trials
that have investigated the efficacy of anti-HER2 therapies took place in the
background of aggressive chemotherapy regimens, thus confounding the
identification of key factors of resistance to the anti-HER2 treatments. Recent
studies, however, have suggested that some HER2-amplified tumors may benefit from
anti-HER2 therapy combined with only a single chemotherapy agent or in the
absence of any chemotherapy. This de-escalation approach, a promising therapeutic
strategy, is currently being explored in the clinic. In this review, we summarize
the major molecular determinants that play a crucial role in influencing tumor
response and resistance to HER2-targeted therapy, and discuss the growing need
for patient stratification in order to facilitate the development of de
escalation strategies using HER2-targeted therapy alone with no chemotherapy.
PMID- 28687444
TI - Long-term follow-up for patients with nonprogressive epilepsia partialis continua
in a single center in China.
AB - Epilepsia partialis continua (EPC) is a rare variant of epilepsy. Cases from
China are rare. We present a case series of seven patients to analyze its
clinical features, imagining findings, etiology, drug use, and long-term outcome
in a single epilepsy center. We made assessments of drug effects twice (Stage I -
when they left our hospital; Stage II in March 2017 - by telephone interviews to
rate their long-term outcome). The mean duration of the second follow-up was
4.8years. Of the seven patients, four patients characterized motor and sensory
EPC and three motor EPC. Local distributions of EPC were: the left face (2
patients), right face (1 patient), left leg (3 patients), right leg and arm (1
patient). CT/MR was abnormal in four, normal in two, and not available in one
patient. EEG abnormalities commonly consisted of spike-waves, sharp-waves (or)
slow wave activity, and periodic lateralized epileptiform discharges. They were
all nonprogressive EPC (encephalitis: 2; tumor: 2; head trauma: 1; and not found
in 2 cases). In our observations, topiramate might be effective in patients with
facial muscles continuous jerking, while carbamazepine in cases of limbs
continuous myotonia. Our cases had favorable long-term outcome. Thus, our cases'
etiology differentiated from other regions. Some drugs used by referring to EPC
distributions might help to control EPC and their outcome were usually favorable.
PMID- 28687445
TI - Factors affecting the survival following surgical treatment of chronic subdural
haematoma: Single institutional experience.
AB - BACKGROUND: Chronic subdural haematoma (CSDH) is one of the most commonly treated
condition in neurosurgery. It affects elderly populations who often have
significant medical co-morbidities resulting in poor prognosis. The study aimed
at identifying clinical factors influencing the survival following surgical
management of CSDH. METHODS: Retrospective study included 267 cases that
underwent surgery for CSDH and followed over 5-year period (2010-2015); data
retrieved with reference to operation details, radiology reports and discharge.
Using logistic and Cox regression analysis, the patient survival data was
analysed with respect to patient demographics, type of surgery, co-morbidities,
anticoagulation treatment, and discharge destination. RESULTS: The overall
survival in the cohort was 37.0months (IQR: 20.0-60.0). The median age of the
patients was 76years (IQR: 66-82) and the median length of hospital stay was
10days (range 1-126days; IQR: 6-17days). The recurrence rate was 6.37% (n=17).
Fifty-three (19.85%) patients recorded deceased on the IPM database as of October
2016 and of those 11 died in hospital. Univariate Cox-regression analysis
revealed increased age (HR: 1.80; 95%CI: 1.04-3.11), length of hospital stay (HR:
2.50; 95%CI: 1.41-4.41) and number of co-morbidities (HR: 2.19; 95%CI: 1.26-3.79)
were associated with poor prognosis. Glasgow coma scale (GCS) at discharge was
found to be significantly associated with survival whilst anticoagulation
treatment did not. Multivariate analysis confirmed similar findings significant
statistically. CONCLUSION: Age at admission, median length of hospital stay,
number of co-morbidities, GCS at discharge and discharge destination have been
found to influence survival significant statistically.
PMID- 28687446
TI - Preservation of hormonal function by identifying pituitary gland at endoscopic
surgery.
AB - OBJECTIVE: The endonasal endoscopic approach has been established for perisellar
tumor surgery with a higher resection rate and reduced complications. We analyzed
the potential to identify the pituitary gland under endoscopic view, at surgery
and see its relation to postoperative hormonal insufficiency in endonasal
endoscopic procedures. METHODS: Between January 2011 and January 2014, 70 cases
of pituitary adenomas with preoperative intact pituitary function underwent
endoscopic endonasal transsphenoidal procedures for intrasellar pathologies.
Endocrinologists and neurosurgeons followed these patients prospectively. Special
attention was paid to intraoperative identification of gland tissue, surgical
complications, degree of resection and postoperative hormonal insufficiency.
RESULTS: The pituitary gland was identified in 57 out of 70 procedures (81.4%).
Eleven percent (8 of 70 patients) had persistent pituitary insufficiency. Two of
these 8 patients belonged to the group with pituitary gland identification (2 out
of 57); thus, when the pituitary gland was identified during the procedure
postoperative hormonal insufficiency was seen in 3.5% of cases. Failure of
pituitary gland identification presented with hormonal insufficiency of 46.2%. In
analysis with Fisher's exact test, there was a high significant correlation
between the identification of the pituitary gland intraoperatively and normal
pituitary function postoperatively (p<0.005). On follow up radical tumor
resection was seen in 88% (62 of 70 patients). CONCLUSIONS: This study indicates
that identification and preservation of pituitary gland tissue and function is
possible in endoscopic transsphenoidal surgery. This preservation of gland tissue
is a positive predictor of postoperative normal pituitary function.
PMID- 28687447
TI - Repetitive transcranial magnetic stimulation of the supplementary motor area in
treatment-resistant obsessive-compulsive disorder: An open-label pilot study.
AB - Obsessive-compulsive disorder (OCD) is a severely distressing disorder
represented by obsessions and compulsions. A significant proportion of OCD
patients fail to improve with conventional treatment methods. Repetitive
transcranial magnetic stimulation (rTMS) has been proposed as an alternative for
OCD treatment. Functional neuroimaging studies indicate that OCD is associated
with increased activity in the supplementary motor area (SMA), a region that
plays an important role in the pathophysiology of this disorder. In this study,
we assessed the efficacy of augmentation with 1Hz rTMS over the SMA in treatment
resistant OCD patients. The participants received 1Hz rTMS over the SMA in 20
daily sessions for 4weeks. We observed significant reduction in Yale-Brown
Obsessive Compulsive Scale (Y-BOCS) score at the 4th week of the treatment.
Reduction in compulsion contributed to the reduction of global Y-BOCS whereas
there was no significant reduction in obsession. Clinical global impression
global improvement also showed significant change at the 2nd and 4th week of the
treatment. No additional significant changes or significant adverse effects were
seen. These findings suggest that 1Hz rTMS over the SMA can be an efficient and
safe add-on therapeutic method in treatment-resistant patients with OCD. Further
controlled studies in larger samples are required to confirm the effect of 1Hz
rTMS over the SMA in OCD.
PMID- 28687448
TI - Effects of low-level prenatal lead exposure on child IQ at 4 and 8 years in a UK
birth cohort study.
AB - BACKGROUND: The association between childhood exposure to lead (Pb) and deficits
in cognitive function is well established. The association with prenatal
exposure, however, is not well understood, even though the potential adverse
effects are equally important. OBJECTIVES: To evaluate the association between
low prenatal exposure to lead and IQ in children, to determine whether there were
sex differences in the associations, and to evaluate the moderation effect of
prenatal Pb exposure on child IQ. METHODS: Whole blood samples from pregnant
women enrolled in ALSPAC (n=4285) and from offspring at age 30 months (n=235)
were analysed for Pb. Associations between prenatal blood lead concentrations (B
Pb) and child IQ at age 4 and 8 years (WPPSI and WISC-III, respectively) were
examined in adjusted regression models. RESULTS: There was no association of
prenatal lead exposure with child IQ at 4 or 8 years old in adjusted regression
models, and no moderation of the association between child B-Pb and IQ. However,
there was a positive association for IQ at age 8 years in girls with a predicted
increase in IQ (points) per 1MUg/dl of: verbal 0.71, performance 0.57, total
0.73. In boys, the coefficients tended to be negative (-0.15, -0.42 and -0.29
points, respectively). CONCLUSION: Prenatal lead exposure was not associated with
adverse effects on child IQ at age 4 or 8 years in this study. There was,
however, some evidence to suggest that boys are more susceptible than girls to
prenatal exposure to lead. Further investigation in other cohorts is required.
PMID- 28687449
TI - JP8 exposure and neurocognitive performance among US Air Force personnel.
AB - Petroleum-based fuels such as jet propellant (JP) 4, JP5, JP8, and jet A1 (JetA)
are among the most common occupational chemical exposures encountered by military
and civilian workforces. Although acute toxicity following high-level exposures
to JP8 and similar chemical mixtures has been reported, the relationship between
persistent low-level occupational exposures to jet fuels and both acute and
longer-term central nervous system (CNS) function has been comparatively less
well characterized. This paper describes results of neurocognitive assessments
acquired repeatedly across a work week study design (Friday to Friday) as part of
the Occupational JP8 Exposure Neuroepidemiology Study (OJENES) involving U.S. Air
Force (AF) personnel with varying levels of exposure to jet fuel (JP8). JP8
exposure levels were quantified using both personal air monitoring and urinary
biomarkers of exposure. Neurocognitive performance was evaluated using an
objective, standardized battery of tests. No significant associations with
neurocognitive performances were observed between individuals having regular
contact and those with minimal/no direct contact with JP8 (measured by average
work week levels of personal breathing zone exposure). Also, no significant
findings were noted between repeated measures of absorbed dose (multi-day pre
shift urinary 1- and 2-naphthol) and reduced proficiency on neurocognitive tasks
across the work week. Results suggest that occupational exposure to lower (than
regulated standards) levels of JP8 do not appear to be associated with acute,
measurable differences or changes in neurocognitive performance.
PMID- 28687450
TI - Role of androgens in the ovary.
AB - It has been well established for decades that androgens, namely testosterone (T)
plays an important role in female reproductive physiology as the precursor for
oestradiol (E2). However, in the last decade a direct role for androgens, acting
via the androgen receptor (AR), in female reproductive function has been
confirmed. Deciphering the specific roles of androgens in ovarian function has
been hindered as complete androgen resistant females cannot be generated by
natural breeding. In addition, androgens can be converted into estrogens which
has caused confusion when interpreting findings from pharmacological studies, as
observed effects could have been mediated via the AR or estrogen receptor. The
creation and analysis of genetic mouse models with global and cell-specific
disruption of the Ar gene, the sole mediator of pure androgenic action, has now
allowed the elucidation of a role for AR-mediated androgen actions in the
regulation of normal and pathological ovarian function. This review aims to
summarize findings from clinical, animal, pharmacological and novel genetic AR
mouse models to provide an understanding of the important roles androgens play in
the ovary, as well as providing insights into the human implications of these
roles.
PMID- 28687451
TI - Possible roles for glucocorticoid signalling in breast cancer.
AB - Our understanding of breast cancer biology, and our ability to manipulate breast
cancers have grown exponentially in the last 20 years. Much of that expansion has
focused on the roles of steroids in driving these neoplasms. Initially this
research focused on estrogens and progesterone receptors, and more recently on
androgen actions in breast cancers. This review aims to make the case for
glucocorticoids as the next essential steroid subclass that contributes
significantly to our understanding of steroidogenic regulation of these
neoplasms. Glucocorticoids have the potential to play multiple roles in the
regulation of breast cancers including their control of cellular differentiation,
apoptosis and proliferation. Beyond this they also act as a master integrator of
organ homeostats in relation to such as circadian rhythms and stress responses.
Therefore a better understanding of glucocorticoids and breast cancer could help
to explain some of the epidemiological links between circadian disruption and/or
stress and breast cancer development. Finally glucocorticoids are currently used
during chemotherapeutic treatment in breast cancer therapy and yet results of
various studies suggest that this may have an adverse impact on treatment
success. This review aims to summarise the current evidence for glucocorticoids
as actors in breast cancer and then suggest future essential approaches in order
to determine the roles of glucocorticoids in this disease.
PMID- 28687452
TI - A Conceptual Framework for Integrated Pest Management.
AB - The concept of integrated pest management (IPM) has been accepted and
incorporated in public policies and regulations in the European Union and
elsewhere, but a holistic science of IPM has not yet been developed. Hence,
current IPM programs may often be considerably less efficient than the sum of
separately applied individual crop protection actions. Thus, there is a clear
need to formulate general principles for synergistically combining traditional
and novel IPM actions to improve efforts to optimize plant protection solutions.
This paper addresses this need by presenting a conceptual framework for a modern
science of IPM. The framework may assist attempts to realize the full potential
of IPM and reduce risks of deficiencies in the implementation of new policies and
regulations.
PMID- 28687453
TI - Cerebellar stroke presenting with isolated dizziness: Brain MRI in 136 patients.
AB - OBJECTIVE: To evaluate occurrence of cerebellar stroke in Emergency Department
(ED) presentations of isolated dizziness (dizziness with a normal exam and
negative neurological review of systems). METHODS: A 5-year retrospective study
of ED patients presenting with a chief complaint of "dizziness or vertigo",
without other symptoms or signs in narrative history or on exam to suggest a
central nervous system lesion, and work-up included a brain MRI within 48h.
Patients with symptoms commonly peripheral in etiology (nystagmus, tinnitus, gait
instability, etc.) were included in the study. Patient demographics, stroke risk
factors, and gait assessments were recorded. RESULTS: One hundred and thirty-six
patients, who had a brain MRI for isolated dizziness, were included. There was a
low correlation of gait assessment between ED physician and Neurologist (49
patients, Spearman's correlation r2=0.17). Based on MRI DWI sequence, 3.7% (5/136
patients) had acute cerebellar strokes, limited to or including, the medial
posterior inferior cerebellar artery vascular territory. In the 5 cerebellar
stroke patients, mean age, body mass index (BMI), hemoglobin A1c, gender
distribution, and prevalence of hypertension were similar to the non-cerebellar
stroke patient group. Mean LDL/HDL ratio was 3.63+/-0.80 and smoking prevalence
was 80% in the cerebellar stroke group compared to 2.43+/-0.79 and 22%
(respectively, p values<0.01) in the non-cerebellar stroke group. CONCLUSIONS:
Though there was preselection bias for stroke risk factors, our study suggests an
important proportion of cerebellar stroke among ED patients with isolated
dizziness, considering how common this complaint is.
PMID- 28687454
TI - A comparison of perceived acceptable missed diagnosis rates for high-risk
emergency medicine diagnoses: A brief report.
PMID- 28687455
TI - In vitro and in vivo antimicrobial activity of a synthetic peptide derived from
the C-terminal region of human chemokine CCL13 against Pseudomonas aeruginosa.
AB - Chemokines are important mediators of immunological responses during inflammation
and under steady-state conditions. In addition to regulating cell migration, some
chemotactic cytokines have direct effects on bacteria. Here, we characterized the
antibacterial ability of the synthetic oligopeptide CCL1357-75, which corresponds
to the carboxyl-terminal region of the human chemokine CCL13. In vitro
measurements indicated that CCL1357-75 disrupts the cell membrane of Pseudomonas
aeruginosa through a mechanism coupled to an unordered-helicoidal conformational
transition. In a murine pneumonic model, CCL1357-75 improved mouse survival and
bacterial clearance and decreased neutrophil recruitment, proinflammatory
cytokines and lung pathology compared with that observed in untreated infected
animals. Overall, our study supports the ability of chemokines and/or chemokine
derived oligopeptides to act as direct defense agents against pathogenic bacteria
and suggests their potential use as alternative antibiotics.
PMID- 28687456
TI - Increased oxidative stress and deficient antioxidant levels may be involved in
the pathogenesis of idiopathic recurrent acute pancreatitis.
AB - BACKGROUND: Increased Oxidative Stress (OS) is implicated in the pathogenesis of
Chronic Pancreatitis (CP). Whether or not OS contributes to disease progression
through the stages of Recurrent Acute Pancreatitis(RAP), to CP is not known.
Increased OS, if present in RAP could be an important therapeutic target in
preventing progression of RAP to CP. OBJECTIVE: To assess the oxidative stress
and antioxidant status in patients with idiopathic RAP. METHODS: 50 consecutive
patients with Idiopathic Recurrent Acute Pancreatitis (IRAP) were included.
Markers of OS [4-hydroxynonenol (4-HNE), malondialdehyde (MDA) and serum SOD (S
SOD)] and antioxidant status [ferric reducing the ability of plasma (FRAP),
Glutathione peroxidase (GPX) and Vitamin C (Vit C)] were measured in quiescent
phase and during an episode of pancreatitis. Their levels were compared with
those in age and sex matched healthy controls and patients with CP. RESULTS: The
mean age of patients with IRAP was 22.2 +/- 7.7 years and 39 (78%) were males.
Levels of 4-HNE were significantly increased in patients with IRAP compared with
healthy controls (3.03 +/- 2.35 vs. 2.12 +/- 1.29 ng/ml; p = 0.03) and were even
higher during an episode of acute pancreatitis (5.21 +/- 3.51 ng/ml; p = 0.03).
Antioxidant levels were reduced in IRAP compared with healthy controls as
measured by FRAP (707.0 +/- 144.9 vs. 528.8 +/- 120.0 MUmol/Fe2+liberated; p =
0.0001) and GPX (1472 +/- 375.7 vs. 910.0 +/- 558.5 pg/ml; p = 0.001). OS and
antioxidant profiles were similar in IRAP and CP with no significant difference.
CONCLUSION: OS is increased in patients with IRAP, more so during an acute
episode. Antioxidant levels are also reduced suggesting that OS may play a role
in the pathogenesis of IRAP and its progression to CP.
PMID- 28687457
TI - In vitro and in vivo assessment of newer quinoxaline-oxadiazole hybrids as
antimicrobial and antiprotozoal agents.
AB - A new series of N-(substituted-phenyl)-2-[5-(quinoxalin-2-yloxymethyl)-[1,3,4]
oxadiazol-2-ylsulfanyl]-acetamides (5a-o) was designed and synthesised from the
parent compound 2-hydroxy quinoxaline (1) through a multistep reaction sequence
and was characterised by spectral and elemental analyses. All of the compounds
synthesised were evaluated for their antimicrobial and antiprotozoal activities.
The results revealed that quinoxaline-based 1,3,4-oxadiazoles displayed promising
antibacterial, antifungal and anti-Trypanosoma cruzi activities compared with
reference drugs, particularly the lead compound 5l in a short-term in vivo model
in T. cruzi.
PMID- 28687458
TI - Effectiveness of Screening Modalities in Colorectal Cancer: A Network Meta
Analysis.
AB - The aim of the study was to evaluate on the effectiveness of screening modalities
in the prevention of colorectal cancer (CRC) occurrence and deaths. General meta
analysis was performed to produce pooled estimates of the effect of CRC incidence
and mortality using a search of PubMed, Web of Science, and the Cochrane Library
for eligible studies from January 1992 to March 2016. A network meta-analysis was
performed to synthetically compare the effectiveness of 5 frequently used
screening modalities. A total of 44 studies with a focus on mortality from CRC
using different screening methods were included. General meta-analysis showed
that fecal immunohistochemical testing (FIT), flexible sigmoidoscopy (FS),
colonoscopy, combination of fecal occult blood testing and FS screening
respectively reduced CRC mortality by 59% (relative risk [RR], 0.41; 95%
confidence interval [CI], 0.29-0.59), 33% (RR, 0.67; 95% CI, 0.58-0.78), 61% (RR,
0.39; 95% CI, 0.31-0.50), 38% (RR, 0.62; 95% CI, 0.42-0.91) compared with no
screening, whereas guaiac fecal occult blood testing (gFOBT) reduced CRC-related
mortality by 14% (RR, 0.86; 95% CI, 0.82-0.90). Subgroup analysis showed that
summary estimates of reduction in distal CRC mortality and proximal CRC mortality
were 26% (95% CI, 62%-89%) and 10% (95% CI, 83%-98%). A network meta-analysis
revealed rank probability analysis in which the colonoscopy had a 94.6%
probability of being the most effective examination to reduce CRC mortality. In
addition, the network meta-analysis estimated odds ratio, which was a 79%
reduction (95% CI, 0.09-0.60) in CRC mortality when screening with FIT was
compared with annual or biennial gFOBT and colonoscopy was approximately 80% more
effective than gFOBT for reducing CRC mortality (RR, 0.25; 95% CI, 0.13-0.54).
Analysis of the effects of different screening methods showed that there was a
significant reduction in the incidence of colon cancer, excluding gFOBT. This
meta-analysis confirmed that gFOBT, FIT, FS, and colonoscopy were all effective
in preventing CRC deaths and a major reduction in distal but not proximal CRC
mortality was found. In addition, they were more effective in preventing CRC
incidence in addition to gFOBT. The network meta-analysis suggests that
colonoscopy is the most effective screening for preventing CRC deaths.
PMID- 28687459
TI - Mouse models of nonalcoholic steatohepatitis in preclinical drug development.
AB - Nonalcoholic fatty liver disease (NAFLD) has become the most common cause of
chronic liver disease in the Western world. NAFLD is a complex spectrum of liver
diseases ranging from benign hepatic steatosis to its more aggressive
necroinflammatory manifestation, nonalcoholic steatohepatitis (NASH). NASH
pathogenesis is multifactorial and risk factors are almost identical to those of
the metabolic syndrome. This has prompted substantial efforts to identify novel
drug therapies for correcting underlying metabolic deficits, and to prevent or
alleviate hepatic fibrosis in NASH. Available mouse models of NASH address
different aspects of the disease, have varying clinical translatability, and,
therefore, also show different utility in drug discovery.
PMID- 28687460
TI - 2016 in review: FDA approvals of new molecular entities.
AB - An overview of drugs approved by FDA in 2016 reveals dramatic disruptions in long
term trends. The number of new molecular entities (NMEs) dropped, reflecting the
lowest rate of small-molecule approvals observed in almost five decades. In
addition, the pace of industry consolidation slowed substantially. The impact of
mergers and acquisitions decreased the total number of organizations with past
approval experience and continued research and development (R&D) activities to
102, divided evenly between more established pharmaceutical and newer
biotechnology companies. Despite these substantial differences, the industry
continued to pursue regulatory incentives, as evidenced by a continued increase
in the fraction of NMEs approved using an orphan or priority designation, and
almost all oncology drugs approved in 2016 utilized these mechanisms.
PMID- 28687461
TI - Further evidence for major repeaters as a subgroup of suicide attempters.
PMID- 28687462
TI - The effect of tiotropium in combination with olodaterol on house dust mite
induced allergic airway disease.
AB - One of the major goals of asthma therapy is to maintain asthma control and
prevent acute exacerbations. Long-acting bronchodilators are regularly used for
the treatment of asthma patients and in clinical studies the anti-cholinergic
tiotropium has recently been shown to reduce exacerbations in patients with
asthma. So far it is unclear how tiotropium exerts this effect. For this purpose,
we designed an allergen-driven rechallenge model of allergic airway inflammation
in mice, to assess the effectiveness of tiotropium and the long-acting beta-2
adrenoceptor agonist olodaterol on allergen-induced exacerbations of airway
disease. Female C57BL/6J mice were sensitized intranasally (i.n.) with 1 MUg of
house dust mite (HDM) extract followed by a challenge regime (5 consecutive days
10 MUg HDM extract i.n.) after one week. Mice were exposed to a secondary
challenge five weeks after sensitization and were treated i.n. with different
concentrations of tiotropium or olodaterol (1, 10 and 100 MUg/kg) or a
combination thereof (10 MUg/kg each) prior to and during the secondary challenge
period. Three days after the last challenge, bronchoalveolar lavage (BAL) fluid
and lung tissue were collected for flow cytometry and histologic analysis,
respectively. Secondary challenge with HDM extract strongly induced allergic
airway disease reflected by inflammatory cell infiltration and goblet cell
metaplasia. Treatment with tiotropium, but not with olodaterol reduced tissue
inflammation and goblet cell metaplasia in a dose-dependent manner. The
combination of tiotropium and olodaterol was more effective in significantly
reducing tissue inflammation compared to tiotropium treatment alone, and also led
to a decrease in BAL cell counts. These data suggest that in a model of relapsing
allergic airway disease tiotropium directly prevents exacerbations by reducing
inflammation and mucus production in the airways. In addition, the combination of
tiotropium and olodaterol exerts synergistic effects.
PMID- 28687463
TI - Non-asthmatic eosinophilic bronchitis and its relationship with asthma.
AB - Non-asthmatic eosinophilic bronchitis (NAEB) is an important cause of chronic
cough. NAEB shares similar eosinophilic inflammation of airway and response to
corticosteroids with asthma. However, in contrast to asthma, NAEB subjects have
no airflow obstruction and airway hyperresponsiveness. The pathogenesis of NAEB
are involved with many inflammatory cells such as eosinophils, lymphocytes, mast
cells, cytokines and inflammatory mediators, includingTh2 cytokines, histamine,
leukotrines, prograndins and oxidative stress. The different locations of
inflammatory cells and the inflammatory mediators level may explain this
difference between EB and asthma. There is no study on dose and duration of
treatment. On the prognosis of NAEB, long term follow-up study suggested that
NAEB should be a distinct entity rather than an early stage of asthma or COPD.
The relapse rate is high after treatment. Assessing sputum eosinophils after
treatment is useful to identify those at risk of relapse.
PMID- 28687464
TI - Antibiotic stewardship in the retail clinic setting: Implementation in 1100
clinics nationwide.
AB - In light of increasing antibiotic resistance and a slowed antibiotic development
pipeline, stewardship is more urgent than ever. To date, most stewardship
guidelines and best practice recommendations for implementation focus on local or
regional health care organizations. CVS MinuteClinic has implemented a
consistent, evidence-based stewardship approach in its >1100 clinics in 33
states. The approach is associated with higher quality antibiotic use than that
in primary care practices and emergency departments. Given MinuteClinic's scale,
sharing this approach and lessons learned may assist other organizations in
implementing large-scale stewardship programs that foster judicious use of
antibiotics for the public's health.
PMID- 28687465
TI - On the way to find a cure: Purging latent HIV-1 reservoirs.
AB - Introduction of cART in 1996 has drastically increased the life expectancy of
people living with HIV-1. However, this treatment has not allowed cure as
cessation of cART is associated with a rapid viral rebound. The main barrier to
the eradication of the virus is related to the persistence of latent HIV
reservoirs. Evidence is now accumulating that purging the HIV-1 reservoir might
lead to a cure or a remission. The most studied strategy is the so called "shock
and kill" therapy. This strategy is based on reactivation of dormant viruses from
the latently-infected reservoirs (the shock) followed by the eradication of the
reservoirs (the kill). This review focuses mainly on the recent advances made in
the "shock and kill" therapy. We believe that a cure or a remission will come
from combinatorial approaches i.e. combination of drugs to reactivate the dormant
virus from all the reservoirs including the one located in sanctuaries, and
combination of strategies boosting the immune system. Alternative strategies
based on cell and gene therapy or based in inducing deep latency, which are
evoked in this review reinforce the idea that at least a remission is attainable.
PMID- 28687466
TI - Cerebrospinal fluid volume does not have etiological role in the incidence of
positional skull deformities.
AB - BACKGROUND: Positional skull deformities (PSD) are becoming a daily health
concern for craniofacial surgeons. Several reports have indicated that
cerebrospinal fluid (CSF) space increases on computed tomography (CT) scans of
infants suffering from PSD, suggesting a potential causal link. Here, we describe
a semi-automatic method to estimate total brain and CSF volumes quantitatively.
We tested the potential correlation between total CSF volume and the occurrence
of PSD. METHODS: A single-center retrospective study was carried out using 79 CT
scans of PSD and 60 CT scans of control subjects. The endocranium was segmented
automatically using a three-dimensional deformable surface model, and the brain
was segmented using a semi-automatic threshold-based method. Total CSF volume was
estimated based on the difference between endocranial and brain volumes. RESULTS:
Automatic segmentation of the endocranium was possible in 75 CT scans. Semi
automatic brain and CSF volume evaluations were performed in 40 CT scans of
infants with PSD (18 = occipital plagiocephaly, 11 = fronto-occipital
plagiocephaly, and 11 = posterior brachycephaly) and in six control CT scans.
Endocranial and total CSF volumes were not significantly different between
patients with PSD and controls. The occipital plagiocephaly group had an enlarged
brain volume compared with that in patients in the other groups. CONCLUSIONS:
Total CSF volume did not change in infants with PSD, and the results do not
support a role for volume changes in CSF in the etiology of PSD. Macrocephaly in
patients with occipital plagiocephaly may be a specific etiological factor
compared with that in other PSDs.
PMID- 28687467
TI - What is the effect of anti-resorptive drugs (ARDs) on the development of
medication-related osteonecrosis of the jaw (MRONJ) in osteoporosis patients: A
systematic review.
AB - PURPOSE: To conduct a systematic review of the literature to detect the effect of
anti-resorptive drugs (ARDs) and their administration characteristics in the
development of medication-related osteonecrosis of the jaw (MRONJ) in
osteoporosis patients. METHODS: Systematic search in PubMed, Web of Sciences and
Cochrane Library was performed for relevant studies to July 2016. Population
variables (age, gender, comorbidities, medications, preceding events, number of
patients with MRONJ), ARDs and clinical variables were abstracted independently
from these articles. RESULTS: The 44 eligible studies described 680 MRONJ cases
in osteoporotic patients. The mean age of MRONJ patients was 69.7 +/- 5.2 years.
It was more common in females. Mandible was the most common site. Alendronate was
the most frequently administered ARD. Oral route of administration was noted in
86.7% of the patients. The mean duration of BPs intake was 50.4 +/- 19 months.
Extraction was the most frequently preceding event followed by dentoalveolar
surgery. Corticosteroids or immunosuppressants were the most common concomitant
medications in MRONJ. CONCLUSION: A long duration of ARDs administration seems to
be an important risk factor in MRONJ development. Patients under treatment with
corticosteroids or immunosuppressants might be at a higher risk even if the BPs
duration is less than 4 years.
PMID- 28687468
TI - Two different techniques of manufacturing TMJ replacements - A technical report.
AB - INTRODUCTION: Presently, during the surgical treatment of the patients in
maxillofacial surgery, one can use various medical implants. Moreover custom made
implants are being used. Replacements may be fitted to the structure and shape of
the human skull owing to CAD/CAM (custom aided design/manufacture) called
customized implants. This study was aimed to report for the first time clinical
material from which custom implants, using two different techniques, were
manufactured to reconstruct the temporomandibular joint (TMJ). MATERIAL AND
METHODS: In this study, eleven patients with an average age of 54 years were
included. All of the patients underwent TMJ reconstruction using direct metal
laser sintering (DMLS) or computer numerical control milling (CNC) techniques for
implant manufacture. Four of the eleven patients had a malignancy diagnosis, and
seven had a benign diagnosis. Patients complained of hypomobility of the TMJ,
facial asymmetry, pain and swelling of the preauricular region. Treatment
included 7 CNC milled implants and 4 implants in DMLS. RESULTS: More metallic
implant parts with a rough surface were associated with the DMLS technique. Post
operational, uneventful healing was observed in all clinical cases during an
average of 26.8 months of follow-up. Three months post-operation, facial nerve
palsy, swallowing disturbances and pain were not observed. Infections, allergic
reactions to materials and re-ankylosis were also not observed. Replacements
received correct forms and functions owing to the CAM techniques. Post
operational maximal interincisal opening improved (p < 0.01) and was not
significantly related to preoperational opening, age, sex, diagnosis or adjuvant
radiotherapy. CONCLUSION: Considering both methods, the feature that
differentiates the manufacture technique is the more subtractive surface
finishing required for the DMLS implant than the CNC implant. Both techniques
resulted the same clinical outcomes and can be used successfully in patients with
neoplastic lesions and other TMJ disorders. Unfortunately, DMLS is more
vulnerable to fracture.
PMID- 28687469
TI - Endoscope-assisted neurectomy and inferior alveolar nerve avulsion in treating
trigeminal neuralgia.
AB - OBJECTIVE: To explore endoscope-assisted surgical treatment for idiopathic
trigeminal neuralgia (TN), with neurectomy and avulsion of the inferior alveolar
nerve (IAN), when patients are not willing to undergo intracranial procedures.
CLINICAL MATERIALS AND METHODS: Five TN patients with inferior alveolar neuralgia
in the mandibular branch were admitted; endoscope-assisted inferior alveolar
neurectomy and avulsion was performed for TN treatment. Clinical observation and
postoperative follow-up were conducted. RESULTS: After the operation, all
patients had complete relief of pain, with mild postoperative swelling, limited
mouth opening, and fast recovery. Patients were followed up for 3-24 months.
Facial numbness and paresthesia were felt in the IAN distribution area of the
operated side, with no recurrence. CONCLUSION: Endoscope-assisted neurectomy and
avulsion of the IAN is a safe surgical method to treat TN in the mandibular
branch when craniotomy is contraindicated or when patients decline neurosurgical
options. It is effective in pain relief, with limited invasiveness and speedy
recovery.
PMID- 28687470
TI - Carotid body tumors: Surgical experience in 215 cases.
AB - INTRODUCTION: Carotid body tumors (CBT) are very unusual neck lesions. However,
at high altitudes, they are less rarely found. This study intended to review our
experience in diagnosis and surgical treatment of these lesions. MATERIALS AND
METHODS: Among 242 clinically diagnosed CBT, 215 tumors, arising in and
retrospectively studied. All patients came from the Andean plateaux. Mean age was
52.5 years, 180 were females, and mean size was 4.21 cm. Shamblin type
distribution, described in 187 patients, was: Type I 29(15%), type II 118(63%)
and type III 40(22%). A correct preoperative diagnosis of CBT was made in 95% of
the patients, based on clinical grounds and imaging studies. Complete CBT
resection was performed in 209 tumors (97%). Twenty-three (11%) accidental
preoperative vessel injuries were successfully repaired. Preoperative blood
transfusion was used in only 16 cases. RESULTS: There was no operative mortality.
Postoperative complications occurred in 59(27.5%) procedures, mostly minor and
related to cranial nerve dysfunction. No stroke occurred in any patient. Seven
(3%) cases were malignant. CONCLUSION: A systematic surgical technique allowed us
to perform a complete CBT resection in most patients, unusual operative vascular
accidents, low morbidity and no mortality.
PMID- 28687471
TI - Does the postural variable affect the determination of balance compensation level
in vestibular schwannoma patients?
AB - Previous sensory organization test (SOT) outcomes provided evidences that the
vestibular schwannoma (VS) removal led to acute and slow changes in the ability
to use vestibular cues for balance control. However, the assumptions behind the
equilibrium score (ES) are somewhat controversial within the literature.
Therefore, we compared the time-course of balance control in eighteen VS patients
across different postural variables. Analyses of variance and unsupervised
clustering (k-means) were used to compare the whole dataset of four postural
variables: ES, a modified ES which factored in the time before a fall (cES), the
mean amplitude (MA) and the mean velocity (MV) of center of pressure
displacements. Early after surgery, postural performances significantly decreased
(p < 0.01), especially when vestibular cues are predominant, with lower ES (12.5
+/- 22.8%) and cES (26.6 +/- 16.7%) and higher MA (27.7 +/- 7.1 mm) and MV (95.2
+/- 53.2 mm.s-1) than before or three months after surgery. For each postural
variable, the k-means clustering divided the whole dataset into two clusters:
cluster #1 corresponded to a SOT with low sway amplitude and cluster #2 with high
sway amplitude and falls. Overall, whatever the selected postural variable, the
main recovery profile of VS patients was highlighted, thus surpassing the
ambiguities inherent of the ES calculation.
PMID- 28687472
TI - Development of an instrumented spinal cord surrogate using optical fibers: A
feasibility study.
AB - In vitro replication of traumatic spinal cord injury is necessary to understand
its biomechanics and to improve animal models. During a traumatic spinal cord
injury, the spinal cord withstands an impaction at high velocity. In order to
fully assess the impaction, the use of spinal canal occlusion sensor is
necessary. A physical spinal cord surrogate is also often used to simulate the
presence of the spinal cord and its surrounding structures. In this study, an
instrumented physical spinal cord surrogate is presented and validated. The
sensing is based on light transmission loss observed in embedded bare optical
fibers subjected to bending. The instrumented surrogate exhibits similar
mechanical properties under static compression compared to fresh porcine spinal
cords. The instrumented surrogate has a compression sensing threshold of 40% that
matches the smallest compression values leading to neurological injuries. The
signal obtained from the sensor allows calculating the compression of the spinal
cord surrogate with a maximum of 5% deviation. Excellent repeatability was also
observed under repetitive loading. The proposed instrumented spinal cord
surrogate is promising with satisfying mechanical properties and good sensing
capability. It is the first attempt at proposing a method to assess the internal
loads sustained by the spinal cord during a traumatic injury.
PMID- 28687473
TI - Brain functional alterations in Type 2 Diabetes - A systematic review of fMRI
studies.
AB - Type 2 Diabetes (T2DM) is emerging as a major global health issue. T2DM can
adversely affect cognition and increase dementia risk. This systematic review
aimed to examine the functional brain changes that may underlie cognitive
dysfunction in adults with T2DM. Studies were restricted to those which used
functional magnetic resonance imaging (fMRI). Nineteen independent studies were
identified, mostly comprised of middle aged or older adults. Resting-state
studies demonstrated that compared to controls, connectivity of the Default Mode
Network (DMN) was reduced and the majority of task-based studies identified
reduced activation in T2DM patients in regions relevant to task performance.
Abnormalities of low frequency spontaneous brain activity were observed,
particularly in visual regions. As most studies demonstrated that alterations in
fMRI were related to poorer neuropsychological task performance, these results
indicate that functional brain abnormalities in T2DM have consequences for
cognition.
PMID- 28687474
TI - Alfaxalone for maintenance of anaesthesia in ponies undergoing field castration:
continuous infusion compared with intravenous boluses.
AB - OBJECTIVE: To compare alfaxalone as continuous intravenous (IV) infusion with
intermittent IV injections for maintenance of anaesthesia in ponies undergoing
castration. STUDY DESIGN: Prospective, randomized, 'blinded' clinical study.
ANIMALS: A group of 33 entire male Welsh ponies undergoing field castration.
METHODS: After preanaesthetic medication with IV detomidine (10 MUg kg-1) and
butorphanol (0.05 mg kg-1), anaesthesia was induced with IV diazepam (0.05 mg kg
1) followed by alfaxalone (1 mg kg-1). After random allocation, anaesthesia was
maintained with either IV alfaxalone 2 mg kg-1 hour-1 (group A; n = 16) or saline
administered at equal volume (group S; n = 17). When necessary, additional
alfaxalone (0.2 mg kg-1) was administered IV. Ponies were breathing room air.
Using simple descriptive scales, surgical conditions and anaesthesia recovery
were scored. Total amount of alfaxalone, ponies requiring additional alfaxalone
and time to administration, time from induction to end of infusion and end of
infusion to standing were noted. Indirect arterial blood pressure, pulse and
respiratory rates, end-expiratory carbon dioxide partial pressure and arterial
haemoglobin oxygen saturation were recorded every 5 minutes. Data were analysed
using Student t, Mann-Whitney U and chi-square tests, where appropriate (p <
0.05). RESULTS: Total amount of alfaxalone administered after induction of
anaesthesia (0.75 +/- 0.27 versus 0.17 +/- 0.23 mg kg-1; p < 0.0001) and time to
standing (14.8 +/- 4 versus 11.6 +/- 4 minutes; p = 0.044) were higher in group A
compared to group S. Ponies requiring additional alfaxalone boluses [four (group
A) versus seven (group S)] and other measured variables were similar between
groups; five ponies required oxygen supplementation [three (group A) versus two
(group S)]. CONCLUSION AND CLINICAL RELEVANCE: Continuous IV infusion and
intermittent administration of alfaxalone provided similar anaesthesia quality
and surgical conditions in ponies undergoing field castration. Less alfaxalone is
required when used intermittently.
PMID- 28687475
TI - Double jeopardy: Predictors of elevated lethality risk among intimate partner
violence victims seen in emergency departments.
AB - Many intimate partner homicide victims visit emergency departments (EDs) prior to
their deaths, yet their lethality risk is not well understood. eHealth
interventions for intimate partner violence (IPV) improve provider information,
tailor care to victim need and link victims to services. We analyzed ED patients'
lethality risk using one such intervention, Domestic Violence Report and Referral
(DVRR). DVRR records were assessed for 263 female patients aged 16 and older seen
for IPV at an urban, high-traffic, Northern California ED in 2014-15. Multiple
linear regression was used to test the association of children's presence at
home, pregnancy, age, and abuser-victim relationship with victim's lethality risk
using the Danger Assessment (DA) score from the Lethality Risk Assessment for
Intimate Partner Femicide. Differences in means were assessed using t- and F
tests. The mean DA score indicated high lethality risk, with a third of
respondents (33.1%) reporting very high DA scores. Multiple linear regression
models indicated that increasing victim age (beta=0.20/year; 95% CI: 0.11-0.29),
children's presence at home (beta=2.61, 95% CI: 0.63-4.58), and perpetrator
reported as dating partner (beta=4.50, 95% CI: 1.62-7.38) or ex-partner
(beta=4.38, 95% CI: 1.10-7.66) were significantly associated with the DA score
(p<0.05). Use of DA scores as ED risk assessment tools in response to IPV
victimization could help hospital staff and IPV advocates direct resources toward
highest-need patients, improving health outcomes without additional burden on
hospitals. These results also foreground eHealth interventions' utility in
linking providers and IPV advocates and reducing the risk of intimate partner
homicide.
PMID- 28687476
TI - Actin Nanobodies Uncover the Mystery of Actin Filament Dynamics in Toxoplasma
gondii.
AB - While the intracellular parasite Toxoplasma relies on a divergent actomyosin
motor to support unique speeds in directional movement, the dynamics and
architecture of parasite actin filaments remain a much-discussed issue. Using
actin chromobodies, Periz et al. started to unveil how networks of dynamic F
actin connect Toxoplasma progeny and expand in the replicative vacuole.
PMID- 28687477
TI - Prognostic factors and predictors of sorafenib benefit in patients with
hepatocellular carcinoma: Analysis of two phase III studies.
AB - BACKGROUND & AIMS: Sorafenib, an oral multikinase inhibitor, significantly
prolonged overall survival (OS) vs. placebo in patients with unresectable
hepatocellular carcinoma (HCC) in two phase III studies, SHARP (Sorafenib HCC
Assessment Randomized Protocol) and Asia Pacific (AP). To assess prognostic
factors for HCC and predictive factors of sorafenib benefit, we conducted a
pooled exploratory analysis from these placebo-controlled phase III studies.
METHODS: To identify potential prognostic factors for OS, univariate and
multivariate (MV) analyses were performed for baseline variables by Cox
proportional hazards model. Hazard ratios (HRs) and median OS were evaluated
across pooled subgroups. To assess factors predictive of sorafenib benefit, the
interaction term between treatment for each subgroup was evaluated by Cox
proportional hazard model. RESULTS: In 827 patients (448 sorafenib; 379 placebo)
analyzed, strong prognostic factors for poorer OS identified from MV analysis in
both treatment arms were presence of macroscopic vascular invasion (MVI), high
alpha-fetoprotein (AFP), and high neutrophil-to-lymphocyte ratio (NLR; ? vs.
>median [3.1]). Sorafenib OS benefit was consistently observed across all
subgroups. Significantly greater OS sorafenib benefit vs. placebo was observed in
patients without extrahepatic spread (EHS; HR, 0.55 vs. 0.84), with hepatitis C
virus (HCV) (HR, 0.47 vs. 0.81), and a low NLR (HR, 0.59 vs. 0.84). CONCLUSIONS:
In this exploratory analysis, presence of MVI, high AFP, and high NLR were
prognostic factors of poorer OS. Sorafenib benefit was consistently observed
irrespective of prognostic factors. Lack of EHS, HCV, and lower NLR were
predictive of a greater OS benefit with sorafenib. LAY SUMMARY: This exploratory
pooled analysis showed that treatment with sorafenib provides a survival benefit
in all subgroups of patients with HCC; however, the magnitude of benefit is
greater in patients with disease confined to the liver (without extrahepatic
spread), or in those with hepatitis C virus, or a lower neutrophil-to-lymphocyte
ratio, an indicator of inflammation status. These results help inform the
prognosis of patients receiving sorafenib therapy and provide further refinements
for the design of trials testing new agents vs. sorafenib. Clinical Trial
Numbers: NCT00105443 and NCT00492752.
PMID- 28687478
TI - Factors Influencing the Phenotypic Expression of Hypertrophic Cardiomyopathy in
Genetic Carriers.
AB - INTRODUCTION AND OBJECTIVES: Hypertrophic cardiomyopathy (HCM) is a disorder with
variable expression. It is mainly caused by mutations in sarcomeric genes but the
phenotype could be modulated by other factors. The aim of this study was to
determine whether factors such as sex, systemic hypertension, or physical
activity are modifiers of disease severity and to establish their role in age
related penetrance of HCM. METHODS: We evaluated 272 individuals (mean age 49 +/-
17 years, 57% males) from 72 families with causative mutations. The relationship
between sex, hypertension, physical activity, and left ventricular hypertrophy
was studied. RESULTS: The proportion of affected individuals increased with age.
Men developed the disease 12.5 years earlier than women (adjusted median, 95%CI,
17.52 to -6.48; P < .001). Hypertensive patients were diagnosed with HCM later
(10.8 years of delay) than normotensive patients (adjusted median, 95%CI, 6.28
17.09; P < .001). Individuals who performed physical activity were diagnosed with
HCM significantly earlier (7.3 years, adjusted median, 95%CI, -14.49 to -1.51; P
= .016). Sex, hypertension, and the degree of physical activity were not
significantly associated with the severity of left ventricular hypertrophy.
Adjusted survival both free from sudden death and from the combined event were
not influenced by any of the exploratory variables. CONCLUSIONS: Men and athletes
who are carriers of sarcomeric mutations are diagnosed earlier than women and
sedentary individuals. Hypertensive carriers of sarcomeric mutations have a
delayed diagnosis. Sex, hypertension, and physical activity are not associated
with disease severity in carriers of HCM causative mutations.
PMID- 28687480
TI - Ending HIV, hepatitis B, and hepatitis C: what about people with severe mental
illness?
PMID- 28687479
TI - Senescent B cells in aging and age-related diseases: Their role in the regulation
of antibody responses.
AB - Immune cells with a senescence-associated secretory phenotype increase in the
blood of elderly individuals or individuals with age-associated diseases or with
infections. Although senescent immune cells do not proliferate, they are
transcriptionally and metabolically active and affect the microenvironment
through the secretion of pro-inflammatory mediators. An age-driven increase in
senescent B, T and NK cells has been reported and the function of these cells has
been characterized. Results published by different groups have demonstrated that
cell senescence induces the accumulation of terminally-differentiated cells
characterized by the arrest of cell proliferation but with an active secretory
profile which regulates their function through the activation of pathways
integrating senescence and energy-sensing signals. This review will focus on
senescent B cells, their increase in aging, age-associated conditions and
infections. Similarities with other senescent immune cells will be presented and
discussed.
PMID- 28687481
TI - Prevalence and risk factors for HIV, hepatitis B, and hepatitis C in people with
severe mental illness: a total population study of Sweden.
AB - BACKGROUND: Severe mental illness is associated with increased morbidity and
mortality. The elevated risk of blood-borne viruses (BBVs) in people with severe
mental illness is of concern, but the full extent of this problem is unclear. We
aimed to determine the prevalence of and risk factors for BBVs in people with
severe mental illness. METHODS: In this nationwide, population-based, cross
sectional study, we estimated the point prevalence of HIV, hepatitis B (HBV), and
hepatitis C (HCV) in people with severe mental illness, including the total adult
(>=18 years) Swedish population. We defined severe mental illness as a clinical
diagnosis of schizophrenia, schizoaffective disorder, bipolar disorder, or other
psychotic illness according to the Swedish version of the International
Statistical Classification of Diseases version 8, 9, or 10. We used multivariable
logistic regression to determine the odds of BBVs in individuals with severe
mental illness, relative to the general population, and to identify independent
risk factors (age, sex, immigration status, socioeconomic status, education, and
substance misuse) for BBV infection. We also did a sensitivity analysis excluding
BBV diagnoses made before the introduction of the Register for Infection Disease
Control (1997). FINDINGS: Of 6 815 931 adults in Sweden, 97 797 (1.43%)
individuals had a diagnosis of severe mental illness. Prevalence of BBVs was
elevated in people with severe mental illness, of which 230 (0.24%) had HIV, 518
(0.53%) had HBV, and 4476 (4.58%) had HCV. After accounting for sociodemographic
characteristics, the odds of HIV were 2.57 (95% CI 2.25-2.94, p<0.0001) times
higher in people with severe mental illness than in the general population,
whereas the odds of HBV were 2.29 (2.09-2.51, p<0.0001) times higher and the odds
of HCV were 6.18 (5.98-6.39, p<0.0001) times higher. Substance misuse contributed
most to the increased risk of BBV: after adjustment, odds ratios were 1.61 (1.40
1.85, p<0.0001) for HIV, 1.28 (1.16-1.41, p<0.0001) for HBV, and 1.72 (1.67-1.78,
p<0.0001) for HCV. INTERPRETATION: Our results highlight the need to address the
issue of higher prevalence of BBVs in people with severe mental illness and
identify interventions preventing infection. Targeting of comorbid substance
misuse would have particular effect on reduction of BBV prevalence in this
population. FUNDING: Medical Research Council and Swedish Research Council.
PMID- 28687482
TI - Treatment Rationale and Design for J-SONIC: A Randomized Study of Carboplatin
Plus Nab-paclitaxel With or Without Nintedanib for Advanced Non-Small-cell Lung
Cancer With Idiopathic Pulmonary Fibrosis.
AB - We describe the treatment rationale and procedure for a randomized study (J
SONIC; University Hospital Medical Information Network Clinical Trials Registry
identification no., UMIN000026799) of carboplatin plus nanoparticle albumin-bound
paclitaxel (nab-paclitaxel) with or without nintedanib for patients with advanced
non-small cell lung cancer (NSCLC) and idiopathic pulmonary fibrosis (IPF). The
study was designed to examine the efficacy and safety of nintedanib administered
with carboplatin plus nab-paclitaxel versus carboplatin plus nab-paclitaxel alone
in chemotherapy-naive patients with advanced NSCLC associated with IPF. Eligible
patients (enrollment target, n = 170) will be randomized at a 1:1 ratio to
receive 4 cycles of carboplatin (area under the curve, 6 on day 1) plus nab
paclitaxel (100 mg/m2 on days 1, 8, and 15) administered every 3 weeks either
without (arm A) or with (arm B) nintedanib (150 mg twice daily), to be followed
in arm B by single-agent administration of nintedanib (150 mg twice daily). The
present trial is the first randomized controlled study for the treatment of NSCLC
associated with IPF. The goal of the study is to demonstrate that nintedanib
combined with carboplatin plus nab-paclitaxel prolongs the interval to acute
exacerbation of IPF compared with carboplatin plus nab-paclitaxel alone.
PMID- 28687483
TI - Percutaneous Tibial Nerve Stimulation Therapy for Overactive Bladder Syndrome:
Clinical Effectiveness, Urodynamic, and Durability Evaluation.
AB - OBJECTIVE: To evaluate percutaneous tibial nerve stimulation (PTNS)
effectiveness, durability, and impact on the pathophysiology of overactive
bladder syndrome (OAB) in patients who have been previously treated with
antimuscarinics without success. MATERIALS AND METHODS: A prospective study that
included 200 women diagnosed with OAB between 2007 and 2015 at Virgen de la
Victoria University Hospital (Malaga, Spain) was conducted. OAB patients were
treated with PTNS therapy after antimuscarinic treatment failed. To evaluate OAB
symptoms, clinical and urodynamic studies were performed before and after PTNS
treatment. Treatment's success was defined as a reduction of clinical parameters
by >50% and an improvement of at least 2 urodynamic parameters by >50%. The
Kolmogorov-Smirnov test and Student's t test or Wilcoxon test were used based on
the data. A linear correlation analysis and a multivariate linear regression
analysis were performed to determine factors associated with the success of PTNS
therapy. RESULTS: Of the patients, 94% experienced a positive response to PTNS
considering clinical and urodynamic parameters. PTNS benefits were extended by 24
months. We identified daytime urinary frequency (r = -0.165; P = .024; 95%
confidence interval, -0.248 to -0.018) and first sensation of bladder filling (r
= 0.208; P = .030; 95% confidence interval, 0.001-0.028) as significant
independent predictor factors for PTNS success. CONCLUSION: The current data
confirmed a high effectiveness of PTNS improving OAB symptoms through 24 months.
Furthermore, daytime urinary frequency and first sensation of bladder filling act
as a significant independent predictor factors for PTNS success.
PMID- 28687484
TI - Participation of locus coeruleus in breathing control in female rats.
AB - Several evidences indicate that the locus coeruleus (LC) is involved in central
chemoreception responding to CO2/pH and displaying a high percentage of
chemosensitive neurons (>80%). However, there are no studies about the LC
mediated hypercapnic ventilation performed in females. Therefore, we assessed the
role of noradrenergic LC neurons in non-ovariectomized (NOVX), ovariectomized
(OVX) and estradiol (E2)-treated ovariectomized (OVX+E2) rats in respiratory
response to hypercapnia, using a 6-hydroxydopamine (6-OHDA) - lesion model. A
reduction in the number of tyrosine hydroxylase (TH) immunoreactive neurons (51
90% in 3 animals of NOVX group, 20-42% of lesion in 5 animals of NOVX females,
61.3% for OVX and 62.6% for OVX+E2 group) was observed seven days after
microinjection of 6-OHDA in the LC. The chemical lesion of the LC resulted in
decreased respiratory frequency under normocapnic conditions in OVX and OVX+E2
group. Hypercapnia increased ventilation in all groups as consequence of
increases in respiratory frequency (fR) and tidal volume (VT). Nevertheless, the
hypercapnic ventilatory response was significantly decreased in 6-OHDA-NOVX>50%
rats compared with SHAM-NOVX group and with females that had 20-42% of LC lesion.
In OVX and OVX+E2 lesioned groups, no difference in CO2 ventilatory response was
observed when compared to SHAM-OVX and SHAM-OVX+E2 groups, respectively. Neither
basal body temperature (Tb) nor Tb reduction in response to hypercapnia were
affected by E2 treatment, ovariectomy or LC lesion. Thus, our data show that LC
noradrenergic neurons seem to exert an excitatory role on the hypercapnic
ventilatory response in female rats, as evidenced by the results in NOVX animals
with LC lesioned more than 50%; however, this modulation is not observed in OVX
and OVX+E2 rats. In addition, LC noradrenergic neurons of OVX females seem to
provide a tonic excitatory drive to maintain breathing frequency in normocapnia,
and this response may not to be functionally influenced by E2.
PMID- 28687485
TI - Double stranded RNA is processed differently in two oyster species.
AB - Ostreid herpes virus causes serious disease in the Pacific oyster (Crassostrea
gigas), but not in the Sydney Rock Oyster (Saccostrea glomerata). To investigate
differences in disease progression, we injected oysters with double stranded RNA
(dsRNA). dsRNA is known to mimic viral infection, and can evoke immune responses
when Toll-like receptors detect the dsRNA, leading to the production of type 1
interferon and inflammation cytokines. The uptake and processing of dsRNA was
tracked in gill and mantle tissue of Crassostrea gigas and Saccostrea glomerata
after injection of fluorochrome labelled poly (I:C) dsRNA. The two species showed
significant differences in tissue uptake and clearance, and differences in immune
responses confirmed by real time PCR. These results showed that S. glomerata was
more efficient in processing dsRNA than C. gigas, and that the gill tissue is an
important site of dsRNA processing and response.
PMID- 28687487
TI - A brief history of Analytical Biochemistry: An appreciation for Dr. William
Jakoby, Editor-in-Chief from 1986 to 2017.
PMID- 28687486
TI - Red-emitting chimeric firefly luciferase for in vivo imaging in low ATP cellular
environments.
AB - Beetle luciferases have been adapted for live cell imaging where bioluminescence
is dependent on the cellular availability of ATP, O2, and added luciferin.
Previous Photinus pyralis red-emitting variants with high Km values for ATP have
performed disappointingly in live cells despite having much higher relative
specific activities than enzymes like Click Beetle Red (CBR). We engineered a
luciferase variant PLR3 having a Km value for ATP similar to CBR and ~2.6-fold
higher specific activity. The red-emitting PLR3 was ~2.5-fold brighter than CBR
in living HEK293T and HeLa cells, an improvement consistent with the importance
of the Km value in low ATP environments.
PMID- 28687488
TI - Rescuing fluoride-induced damages in liver with gamma aminobutyric acid.
AB - Fluorine poisoning affects human health all over the world and an urgent task is
to develop alleviative medicine to recover or ameliorate the damages to the body.
Here we studied the effects of gamma-aminobutyric acid (GABA), a liver protector
reported previously, on fluoride-induced damage in the mouse liver. Through
microscope imaging of the liver tissue, TUNEL immunostaining, real-time RT-PCR,
enzyme immunoassay and colorimetric method, we found that GABA supplementation
prevented the metabolic toxicity caused by fluoride treatment in mice. This
detoxification was reflected by the reduced oxidative stress and apoptosis,
enhanced neuron protection and liver function. Collectively, this study provided
evidence of the beneficial effects of GABA supplement on liver damage,
implicating its therapeutic potential in fluorosis.
PMID- 28687489
TI - Fas/S1P1 crosstalk via NF-kappaB activation in osteoclasts controls subchondral
bone remodeling in murine TMJ arthritis.
AB - Enhanced turnover of subchondral trabecular bone is a hallmark of rheumatoid
arthritis (RA) and it results from an imbalance between bone resorption and bone
formation activities. To investigate the formation and activation of osteoclasts
which mediate bone resorption, a Fas-deficient MRL/lpr mouse model which
spontaneously develops autoimmune arthritis and exhibits decreased bone mass was
studied. Various assays were performed on subchondral trabecular bone of the
temporomandibular joint (TMJ) from MRL/lpr mice and MRL+/+ mice. Initially,
greater osteoclast production was observed in vitro from bone marrow macrophages
obtained from MRL/lpr mice due to enhanced phosphorylation of NF-kappaB, as well
as Akt and MAPK, to receptor activator of nuclear factor-kappaB ligand (RANKL).
Expression of sphingosine 1-phosphate receptor 1 (S1P1) was also significantly
upregulated in the condylar cartilage. S1P1 was found to be required for S1P
induced migration of osteoclast precursor cells and downstream signaling via
Rac1. When SN50, a synthetic NF-kappaB-inhibitory peptide, was applied to the
MRL/lpr mice, subchondral trabecular bone loss was reduced and both production of
osteoclastogenesis markers and sphingosine kinase (Sphk) 1/S1P1 signaling were
reduced. Thus, the present results suggest that Fas/S1P1 signaling via activation
of NF-kappaB in osteoclast precursor cells is a key factor in the pathogenesis of
RA in the TMJ.
PMID- 28687490
TI - X-ray structure of a protease-resistant mutant form of human galectin-9 having
two carbohydrate recognition domains with a metal-binding site.
AB - Galectin-9 (G9) is a tandem-repeat type beta-galactoside-specific animal lectin
having N-terminal and C-terminal carbohydrate recognition domains (N-CRD and C
CRD, respectively) joined by a linker peptide that is involved in the immune
system. G9 is divalent in glycan binding, and structural information about the
spatial arrangement of the two CRDs is very important for elucidating its
biological functions. As G9 is protease sensitive due to the long linker, the
protease-resistant mutant form of G9 (G9Null) was developed by modification of
the linker peptide, while retaining its biological functions. The X-ray structure
of a mutant form of G9Null with the replacement of Arg221 by Ser (G9Null_R221S)
having two CRDs was determined. The structure of G9Null_R221S was compact to
associate the two CRDs in the back-to-back orientation with a large interface
area, including hydrogen bonds and hydrophobic interactions. A metal ion was
newly found in the galectin structure, possibly contributing to the stable
structure of protein. The presented X-ray structure was thought to be one of the
stable structures of G9, which likely occurs in solution. This was supported by
structural comparisons with other tandem-repeated galectins and the analyses of
protein thermostability by CD spectra measurements.
PMID- 28687491
TI - Site-specific regulation of oral mucosa-recruiting CD8+ T cells in a mouse
contact allergy model.
AB - Contact allergy is a T cell-mediated, delayed-type hypersensitivity generated by
contact exposure of an allergen to the skin and mucosal surface. The clinical
manifestations of allergic responses between the skin and oral mucosa vary and
the differences in immunopathology have not been clarified. We generated hapten
induced contact hypersensitivity (CH) of the buccal mucosa (BM) in parallel
studies with ear skin (ES) CH, and observed several characteristic findings of BM
CH. The BM challenge induced more rapid and more severe inflammation than the ES
challenge, with abundant granulocyte and CD8+ T cell infiltration. However, these
inflammatory responses diminished quickly. Recruiting CD8+ T cells in the BM had
higher ratios of CD62L-CD44low-hi memory-type cells, and showed impaired IFN
gamma, greater PD-1, and comparable Ki-67 expression, suggesting that the
recruiting-proliferating CD8+ T cells were unable to differentiate into effector
T cells and converted into exhausted T cells at the local site. This finding may
explain the rapid recovery of the BM from severe inflammation. Preferentially
greater expression of PD-1 ligand (B7-H1), was observed in the BM epithelium
under the peak inflammation, and the absence of B7-H1 further accelerated CH
responses, suggesting the occurrence of PD-1:B7-H1-mediated immune regulation at
the local site. Our results may facilitate the understanding of the unique
features of contact allergies in the oral mucosa, and guide the development of
new strategies for control of contact allergy.
PMID- 28687492
TI - Molecular characterization of the hydroxylase HmtN at 1.3 A resolution.
AB - Himastatin is a novel antibiotic with antitumor and antibacterial activity. In
the himastatin biosynthesis pathway, HmtN is responsible for the hydroxylation of
the piperazic acid (Pip) motif. Herein, we present the crystal structures of HmtN
(1.3 A), which is the first structure for a cytochrome P450 involved in the
hydroxylation of cyclohexadepsipeptide during himastatin biosynthesis. Structure
analysis indicated that almost all the surface of HmtN has negative electrostatic
potential, only small patches of positive electrostatic potential can be found.
It is worth noting that almost the entire active site of HmtT is negatively
charged, while HmtN active site is composed of positive and negative charge. This
may be relevant to their specific substrate recognition and different catalytic
function. In addition, three channels were observed in HmtN crystal structure;
channel 3 may be essential for substrate ingress and egress from the active site
to the surface, while channel 1 and channel 2 may be the solvent and water
pathway, respectively.
PMID- 28687493
TI - Importance of the surface chemistry of nanoparticles on peroxidase-like activity.
AB - We report the studies on origin of peroxidase-like activity for gold
nanoparticles, as well as the impact from morphology and surface charge of
nanoparticles. For this purpose, we have synthesized hollow gold nanospheres
(HAuNS) and gold nanorods (AuNR) with different morphology and surface chemistry
to investigate their influence on the catalytic activity. We found that citrate
capped HAuNS show catalyzing efficiency in oxidation reaction of 3,3',5,5'
tetramethylbenzidine (TMB) by hydrogen peroxide (H2O2) and it is superior to that
of cetyltrimethylammonium bromide (CTAB)-capped AuNR. The kinetics of catalytic
activities from HAuNS and AuNR were respectively studied under varied
temperatures. The results indicated that surface chemistry rather than morphology
of nanoparticles plays an important role in the catalytic reaction of substrate.
Furthermore, influencing factors such as pH, amount of nanoparticle and H2O2
concentration were also investigated on HAuNS-catalyzed system. The great impact
of nanoparticle surface properties on catalytic reactions makes a paradigm in
constructing nanozymes as peroxidase mimic for sensing application.
PMID- 28687495
TI - Extracellular vesicles: Novel promising delivery systems for therapy of brain
diseases.
AB - Extracellular vesicles (EVs) are cell-derived membrane vesicles virtually
secreted by all cells, including brain cells. EVs are a major term that includes
apoptotic bodies, microvesicles and exosomes. The release of EVs has been
recognized as an important modulator in cross-talking between neurons,
astrocytes, microglia and oligodendrocytes, not only in central nervous system
(CNS) physiology but also in neurodegenerative and neuroinflammatory disease
states as well as in brain tumors, such as glioma. EVs are able to cross the
blood brain barrier (BBB), spread to body fluids and reach distant tissues. This
prominent spreading ability has suggested that EVs can be exploited into several
different clinical applications ranging from biomarkers to therapeutic carriers.
Exosomes, the well-studied group of EVs, have been emerging as a promising tool
for therapeutic delivery strategies due to their intrinsic features, such as the
stability, biocompatibility and stealth capacity when circulating in bloodstream,
the ability to overcome natural barriers and inherent targeting properties. Over
the last years, it became apparent that EVs can be loaded with specific cargoes
directly in isolated EVs or by modulation of producer cells. In addition, the
engineering of its membrane for targeting purposes is expected to allow
generating carriers with unprecedented abilities for delivery in specific organs
or tissues. Nevertheless, some challenges remain regarding the loading and
targeting of EVs for which more research is necessary, and will be discussed in
this review. Recently-emerged promising derivations are also discussed, such as
exosome associated with adeno-associated virus (AAV) vectors (vexosomes),
enveloped protein nanocages (EPNs) and exosome-mimetic nanovesicles. This article
provides an updated review of this fast-progressing field of EVs and their role
in brain diseases, particularly focusing in their therapeutic applications.
PMID- 28687496
TI - Romosozumab increases bone mineral density in postmenopausal Japanese women with
osteoporosis: A phase 2 study.
AB - BACKGROUND: Romosozumab is a monoclonal antibody that inhibits sclerostin and
rapidly increases bone mineral density (BMD) through a dual effect on bone by
increasing bone formation and decreasing bone resorption, as shown in a global
phase 2 study in postmenopausal women with low bone mass. Here, we report the key
results of a phase 2, double-blind, placebo-controlled, dose-ranging study to
assess the efficacy and safety of romosozumab in postmenopausal Japanese women
with osteoporosis. METHODS: Participants were postmenopausal Japanese women with
osteoporosis aged 55-85years with a lumbar spine, total hip, or femoral neck dual
energy X-ray absorptiometry T-score<=-2.5. Women were randomized to receive
placebo or romosozumab (70, 140, or 210mg) subcutaneously once monthly (QM) for
12months. The primary efficacy endpoint was the percentage change from baseline
in lumbar spine BMD at month 12. Secondary efficacy endpoints included the
percentage change from baseline in lumbar spine BMD at month 6, total hip and
femoral neck BMD at months 6 and 12, and serum bone turnover markers procollagen
type 1N-terminal propeptide (P1NP) and C-terminal telopeptide of type 1 collagen
(CTX) at multiple visits. RESULTS: This study enrolled 252 women who had a mean
age of 67.7years and mean T-scores of -2.7, -1.9, and -2.3 at the lumbar spine,
total hip, and femoral neck, respectively. All romosozumab doses significantly
increased BMD at month 12 compared with placebo (p<0.01), with the largest mean
gains from baseline observed with romosozumab 210mg QM (lumbar spine=16.9%, total
hip=4.7%, and femoral neck=3.8%). All doses of romosozumab significantly
increased the levels of bone-formation marker P1NP and reduced the levels of bone
resorption marker CTX by week 1 (p<0.001 vs placebo). In the 210mg QM group, P1NP
levels peaked at month 1 and fell below placebo levels by month 12; CTX levels
were lowest at week 1 and remained below placebo through month 12. The patient
incidences of adverse events and serious adverse events were generally comparable
between treatment groups. CONCLUSIONS: In postmenopausal Japanese women with
osteoporosis, romosozumab treatment resulted in large and significant gains in
BMD from baseline and compared with placebo. Romosozumab 210mg QM showed the
largest gains in BMD and was generally well tolerated. The efficacy and safety of
romosozumab 210mg QM in this phase 2 study of postmenopausal women with
osteoporosis were similar to those in an international phase 2 study.
PMID- 28687497
TI - The Protein Encoded by the CCDC170 Breast Cancer Gene Functions to Organize the
Golgi-Microtubule Network.
AB - Genome-Wide Association Studies (GWAS) and subsequent fine-mapping studies (>50)
have implicated single nucleotide polymorphisms (SNPs) located at the
CCDC170/C6ORF97-ESR1 locus (6q25.1) as being associated with the risk of breast
cancer. Surprisingly, our analysis using genome-wide differential allele-specific
expression (DASE), an indicator for breast cancer susceptibility, suggested that
the genetic alterations of CCDC170, but not ESR1, account for GWAS-associated
breast cancer risk at this locus. Breast cancer-associated CCDC170 nonsense
mutations and rearrangements have also been detected, with the latter being
specifically implicated in driving breast cancer. Here we report that the wild
type CCDC170 protein localizes to the region of the Golgi apparatus and binds
Golgi-associated microtubules (MTs), and that breast cancer-linked truncations of
CCDC170 result in loss of Golgi localization. Overexpression of wild type CCDC170
triggers Golgi reorganization, and enhances Golgi-associated MT stabilization and
acetyltransferase ATAT1-dependent alpha-tubulin acetylation. Golgi-derived MTs
regulate cellular polarity and motility, and we provide evidence that
dysregulation of CCDC170 affects polarized cell migration. Taken together, our
findings demonstrate that CCDC170 plays an essential role in Golgi-associated MT
organization and stabilization, and implicate a mechanism for how perturbations
in the CCDC170 gene may contribute to the hallmark changes in cell polarity and
motility seen in breast cancer.
PMID- 28687499
TI - Response to Intravenous Glucose-Tolerance Test and Risk of Cancer: A Long-Term
Prospective Cohort Study.
AB - BACKGROUND: Impaired glucose regulation, measured with an oral glucose-tolerance
test, has been associated with the risk of cancer. Here, we explored whether the
response to an intravenous glucose-tolerance test (IVGTT) is associated with the
risk of cancer. METHODS: A cohort of 945 healthy men, aged 40-59years in 1972-75,
was followed for 40years. An IVGTT was performed at baseline. Blood samples for
glucose determinations were drawn immediately before glucose injection and
thereafter every 10min for 1h. Associations were assessed with incidence rate
ratios (IRR) and Cox models. FINDINGS: Cancer incidence was higher among men with
10-min glucose levels below the median than in men with levels above the median
(IRR: 1.5, 95% CI: 1.2-1.9). This association remained significant after
adjusting for relevant confounders (HR: 1.6, 95% CI: 1.3-2.1) and when excluding
the first 10years of follow-up to minimize the possibility of reverse causality
(HR: 1.5, 95% CI: 1.2-2.0). INTERPRETATION: Healthy middle-aged males that
responded to an intravenous glucose injection with rapid glucose elimination
during the first phase had an elevated risk of cancer during 40years of follow
up. First phase response to a glucose load might be related to cancer
development.
PMID- 28687500
TI - Analysis of Hemodynamic Changes in Early Stage after Carotid Stenting by
Transcranial Doppler-A Preliminary Study.
AB - BACKGROUND: Cerebral hyperperfusion syndrome or hemodynamic instability, caused
by the hemodynamic changes, often occur within 6 hr after carotid artery stenting
(CAS) The postprocedure cerebral hemodynamic change in the early phase, <6 hr
after CAS, is largely unknown. In this study, we evaluated the cerebral
hemodynamic changes in patients after CAS using transcranial Doppler (TCD).
METHODS: From January 2013 to July 2014, medical records of 61 patients who
underwent CAS were reviewed retrospectively. Among them, 44 patients had TCD
examination before CAS, 1-2 and 3-4 hr after CAS. In the TCD examination, middle
cerebral artery (MCA) peak systolic velocity (PSV) and pulsatility index (PI) on
the ipsilateral and contralateral sides were measured. Blood pressure, MCA PSV,
and PI data were collected and analyzed from the 44 patients who had valid TCD
examinations. RESULTS: Blood pressure was 148.4 +/- 14.5 mm Hg before CAS: 124.5
+/- 13.8 mm Hg 1-2 hr after CAS, and 121.6 +/- 12.6 mm Hg 3-4 hr after CAS. On
the ipsilateral side, the MCA PSV increased from 85.7 +/- 22.8 cm/s before CAS to
101.1 +/- 27.1 cm/s (19.9%, P < 0.001) 1-2 hr after CAS, and 99.7 +/- 27.0 cm/s
(18.2%, P < 0.001) 3-4 hr after CAS. There was no significant difference in MCA
PSV between 1-2 and 3-4 hr after CAS (P = 0.200). The PI increased from 0.871 +/-
0.167 before CAS to 0.941 +/- 0.205 (P = 0.022) 1-2 hr after CAS, and 0.954 +/-
0.218 (P = 0.010) 3-4 hr after CAS. On the contralateral side, there was no
statistically significant PSV increase in the MCA following CAS. CONCLUSIONS: CAS
may induce a significant increase in PSV and PI in the ipsilateral MCA within 4
hr. The MCA PSV increased significantly higher than that on the contralateral
side. The PSV had no significant change between 1-2 and 3-4 hr after CAS.
PMID- 28687494
TI - Sphingolipid abnormalities in cancer multidrug resistance: Chicken or egg?
AB - The cancer multidrug resistance (MDR) phenotype encompasses a myriad of
molecular, genetic and cellular alterations resulting from progressive oncogenic
transformation and selection. Drug efflux transporters, in particular the MDR P
glycoprotein ABCB1, play an important role in MDR but cannot confer the complete
phenotype alone indicating parallel alterations are prerequisite. Sphingolipids
are essential constituents of lipid raft domains and directly participate in
functionalization of transmembrane proteins, including providing an optimal lipid
microenvironment for multidrug transporters, and are also perturbed in cancer.
Here we postulate that increased sphingomyelin content, developing early in some
cancers, recruits and functionalizes plasma membrane ABCB1 conferring a state of
partial MDR, which is completed by glycosphingolipid disturbance and the
appearance of intracellular vesicular ABCB1. In this review, the independent and
interdependent roles of sphingolipid alterations and ABCB1 upregulation during
the transformation process and resultant conferment of partial and complete MDR
phenotypes are discussed.
PMID- 28687501
TI - Endovascular Repair with Periscope Technique for Aortic Dissection with an
Aberrant Right Subclavian Artery.
AB - A type B aortic dissection with an aberrant right subclavian artery is an
uncommon entity. Most cases have been treated by open or hybrid surgery. We
present a case that was managed by endovascular aortic repair with the periscope
technique. A thoracic stent graft was implanted into the aortic arch beyond the
origin of the right subclavian artery. Two overlapping periscope grafts were
placed to maintain perfusion to the right subclavian artery. The presented
technique is a feasible and minimally invasive approach for this rare entity.
PMID- 28687498
TI - Prognostic and Predictive Value of p21-activated Kinase 6 Associated Support
Vector Machine Classifier in Gastric Cancer Treated by 5-fluorouracil/Oxaliplatin
Chemotherapy.
AB - To determine whether p21-activated Kinase (PAK) 6 is a prognostic and predictive
marker in gastric cancer (GC) and to construct a classifier that can identify a
subset of patients who are highly sensitive to 5-fluorouracil/oxaliplatin
chemotherapy. We retrospectively analyzed the expression levels of PAK6,
cyclooxygenase 2, p21WAF1, Ki-67, excision repair cross-complementing gene 1, and
thymidylate synthase in 242 paraffin-embedded GC specimens of the training cohort
by immunohistochemistry. Then, we used support vector machine (SVM)-based methods
to develop a predictive classifier for chemotherapy (chemotherapy score - CS-SVM
classifier). Further validation was performed in an independent cohort of 279
patients. High PAK6 expression was associated with poor prognosis and increased
chemoresistance to 5-FU/oxaliplatin chemotherapy. The CS-SVM classifier
distinguished patients with stage II and III GC into low- and high-CS-SVM groups,
with significant differences in the 5-year disease-free survival (DFS) and
overall survival (OS) in chemotherapy patients. Moreover, chemotherapy
significantly prolonged the DFS and OS of the high CS-SVM patients in the
training and validation cohorts. In conclusion, PAK6 was an independent
prognostic factor and increased chemoresistance. The CS-SVM classifier
distinguished a subgroup of stage II and III patients who would highly benefit
from chemotherapy, thus facilitating patient counseling and individualizing the
management.
PMID- 28687502
TI - Endovascular Treatment of Distal Tears Located in the Reno-Visceral Segment with
Bare-Metal Stents and Coils in a Complicated Type B Aortic Dissection.
AB - The purpose of the study was to provide an endovascular strategy of treating
patent reentries adjacent to visceral branches in the management of aortic
dissections. A 45-year-old male who had received endovascular treatment for a
type B aortic dissection was again admitted for his intermittent abdominal pain.
Distal tears located in the reno-visceral segment were left untreated in the
initial procedure and were thought to be related to the expansion of the false
lumen during follow-up. Another endovascular surgery aiming at sealing these
reentries was then performed using the concept of low-porosity flow-diverting
stents and coiling technique. Postoperative angiogram revealed a significant
decrease in inflow rate through the distal tears, and further computed tomography
scan showed a decrease in maximum aortic diameter during the follow-up. With the
assistance of coils, the low-porosity bare stents showed the potential to
significantly decrease the inflow rate and accelerate the thrombosis of the false
lumen. Clinical success achieved in this case study proposes an endovascular
strategy in treating the reentries without disturbing the adjacent branches,
while its safety and efficacy are still waiting for the verification.
PMID- 28687503
TI - Surgical Management of Congenital Arteriovenous Fistula near Lateral Cranial
Base.
AB - An arteriovenous fistula is an aberrant communication between an artery and a
vein. Here is a case in which risk factors including multiple fistulae, dangerous
location, and high-flow blood occurred simultaneously. The patient is a 13-year
old boy diagnosed with bilateral arteriovenous fistulae between the jugular vein
and carotid artery separately, with cardiac dilatation and pulmonary artery
hypertension. We performed right arteriovenous fistulae resection, ligated the
involved small vessels, and tightened the internal jugular vein. The tiny left
arteriovenous fistulae were treated with transarterial embolism. The blood flow
bruit and swelling of his neck completely disappeared, with clear improvement of
his life quality, the pulmonary artery pressure has dropped from 54 mmHg to 39
mmHg. Surgery is one of the main therapies of arteriovenous fistula currently, we
need to make a balance between good effect and low risk, aiming at early
treatment to avoid serious complications.
PMID- 28687504
TI - Infected Abdominal Aortic Aneurysms Treated with Extra-anatomic Prosthesis Bypass
in the Retroperitoneum.
AB - BACKGROUND: Infected abdominal aortic aneurysms (iAAAs) are rare but life
threatening diseases. The purpose of the present study was to report our
experience of extra-anatomic prosthesis bypass in the retroperitoneum as a
treatment for iAAAs. METHODS: Data of 8 consecutive patients diagnosed with iAAAs
and treated by an extra-anatomic prosthesis bypass in the retroperitoneum were
retrospectively collected. Operative details were as follows: one side of the
retroperitoneal space was selected to build a track, and a bifurcated expanded
polytetrafluoroethylene prosthesis was placed through the track. The proximal end
of the prosthesis was sutured with the normal segment of abdominal aorta proximal
to the infected aneurysm by end-to-end anostomosis. The 2 distal ends of the
prosthesis were, respectively, sutured with the external iliac artery distal to
the aneurysm. The anastomoses were then consolidated with the nearby connective
tissue. After the closure of the retroperitoneum, the infected aneurysm was
incised, and the infected tissue was debrided. Drainage tubes were placed in the
aneurysm sac, which was packed with an omentum flap. All patients received
perioperative antibiotic therapy for a period of time. All 8 patients were
regularly followed up by outpatient observation. RESULTS: Eight patients with
iAAAs underwent an extra-anatomic prosthesis bypass in the retroperitoneum and
debridement of the infected aneurysm. An emergency operation was performed for 1
patient who underwent concomitant gastrointestinal procedures for aortoduodenal
fistula. All 8 patients were definitively diagnosed by one or more sequential
computed tomography scans combined with other methods. The blood or tissue
cultures of all cases were positive in the perioperative period, with Salmonella
(5 cases) being the most common pathogens. Other pathogens included Burkholderia
pseudomallei (2 cases) and Escherichia coli (1 case). All patients survived and
were discharged in 4-5 weeks after their operations. All patients were free from
graft infection during the follow-up period. CONCLUSIONS: The extra-anatomic
prosthesis bypass in the retroperitoneum for treating iAAAs was safe and
effective. Our experience with the procedure may provide a new approach for the
treatment of this disease.
PMID- 28687505
TI - Xiaochaihutang attenuates depressive/anxiety-like behaviors of social isolation
reared mice by regulating monoaminergic system, neurogenesis and BDNF expression.
AB - ETHNOPHARMACOLOGICAL RELEVANCE: Xiaochaihutang (XCHT), as a classical herbal
formula for the treatment of "Shaoyang syndrome" has been demonstrated to exert
an antidepressant effect in multiple animal models of depression as shown in our
previous studies. However, the effects of XCHT on social isolation (SI)-reared
mice have not been investigated. This study aims to explore the effects of XCHT
on depressive/anxiety-like behaviors of SI-reared mice, and its implicated
mechanisms, including alterations in the monoaminergic system, neurogenesis and
neurotrophin expression. MATERIALS AND METHODS: Male C57 BL/6J mice (aged 4 weeks
after weaning) were reared isolatedly for 8 weeks and XCHT (0.8, 2.3, 7.0g/kg)
were given by gavage once a day. Forced swimming test (FST), tail suspension test
(TST), open field test (OFT), elevated-plus maze test (EPM) and intruder-induced
aggression test were used to explore the effects of XCHT on depressive/anxiety
like behaviors of SI-reared mice after administration of XCHT for 6 weeks. HPLC
MS/MS was performed to quantify the levels of neurotransmitters in the
hippocampus by in vivo microdialysis, while western immunoblotting was used to
evaluate the action of XCHT on the synthesis, transport and degradation of
monoamine neurotransmitters. Immunofluorescence was used to study the effects of
XCHT on neurogenesis and neurotrophin expression, including Ki-67, DCX, BrdU and
BDNF. RESULTS: Our results showed that administration of XCHT (0.8, 2.3 and
7.0g/kg) for 6 weeks significantly attenuated the increase in immobility time in
TST and FST, improved the anxiety-like behaviors in OFT and EPM, and improved the
aggressive behaviors of SI-reared mice. XCHT significantly elevated monoamine
neurotransmitters levels and inhibited 5-HT turnover (5-HIAA/5-HT) in hippocampal
microdialysates of SI-reared mice. In addition, we found XCHT enhanced monoamine
neurotransmitter synthesis enzymes (TPH2 and TH) expressions, inhibited serotonin
transporter (SERT) expression and decreased monoamine neurotransmitter
degradation enzyme (MAOA) expression in the hippocampus of SI-reared mice for the
first time. Moreover, XCHT significantly augmented hippocampal neurogenesis and
BDNF expression in hippocampus of SI-reared mice. CONCLUSIONS: Our results showed
for the first time that XCHT improved depressive/anxiety-like behaviors of SI
reared mice by regulating the monoaminergic system, neurogenesis and neurotrophin
expression. The findings indicate that XCHT may have a therapeutic application
for early-life stress model of depression and in turn provide further evidence
supporting XCHT a novel potential antidepressant from a distinct perspective.
PMID- 28687506
TI - Effects of alkaloid-rich extract from Mitragyna speciosa (Korth.) Havil. on
naloxone-precipitated morphine withdrawal symptoms and local field potential in
the nucleus accumbens of mice.
AB - ETHNOPHARMACOLOGICAL RELEVANCE: Mitragyna speciosa (Korth.) Havil. (M. speciosa)
is among the most well-known plants used in ethnic practice of Southeast Asia. It
has gained increasing attention as a plant with potential to substitute morphine
in addiction treatment program. However, its action on the central nervous system
is controversial. AIM OF THE STUDY: This study investigated the effects of M.
speciosa alkaloid extract on naloxone-precipitated morphine withdrawal and neural
signaling in the nucleus accumbens (NAc, brain reward center) of mice. MATERIALS
AND METHODS: The effects of M. speciosa alkaloid extract and mitragynine, a pure
major constituent, on naloxone-precipitated morphine withdrawal were examined.
Male Swiss Albino (ICR) mice were rendered dependent on morphine before injection
with naloxone, a nonspecific opioid antagonist, to induce morphine withdrawal
symptoms. The intensity of naloxone-precipitated morphine withdrawal was assessed
from jumping behavior and diarrhea induced during a period of morphine
withdrawal. To test possible addictive effect of M. speciosa alkaloid extract,
mice were implanted with intracranial electrode into the NAc for local field
potential (LFP) recording. Following M. speciosa alkaloid extract (80mg/kg) and
morphine (15mg/kg) treatment, LFP power spectra and spontaneous motor activity
were analyzed in comparison to control levels. RESULTS: One-way ANOVA and
multiple comparisons revealed that M. speciosa alkaloid extract (80 and 100mg/kg)
significantly decreased the number of jumping behavior induced by morphine
withdrawal whereas mitragynine did not. Additionally, M. speciosa alkaloid
extract significantly decreased dry and wet fecal excretions induced by morphine
withdrawal. LFP analysis revealed that morphine significantly decreased alpha
(9.7-12Hz) and increased low gamma (30.3-44.9Hz) and high gamma (60.5-95.7Hz)
powers in the NAc whereas M. speciosa alkaloid extract did not. Spontaneous motor
activity was significantly increased by morphine but not M. speciosa alkaloid
extract. CONCLUSIONS: Taken together, M. speciosa alkaloid extract, but not
mitragynine, attenuated the severity of naloxone-precipitated morphine withdrawal
symptoms. Neural signaling in the NAc and spontaneous motor activity were
sensitive to morphine but not M. speciosa alkaloid extract. Therefore, treatment
with the M. speciosa alkaloid extract may be useful for opiate addiction
treatment program.
PMID- 28687507
TI - Gastroprotective actions of Taraxacum coreanum Nakai water extracts in ethanol
induced rat models of acute and chronic gastritis.
AB - ETHNOPHARMACOLOGICAL RELEVANCE: Taraxacum coreanum Nakai has been traditionally
used for treating inflammatory diseases including gastrointestinal diseases. AIM
OF THE STUDY: We studied whether water extracts of Taraxacum coreanum Nakai (TCN)
had a protective effect on acute and chronic gastritis induced by ethanol/HCl in
an animal model of gastritis and its mechanism was also explored. MATERIALS AND
METHODS: In the acute study, rats were orally administered 0.15g/mL dextrin
(normal-control), 0.15g/mL dextrin (control), 0.05g/mL TCN (TCN-L), 0.15g/mL TCN
(TCN-H), or 0.01g/mL omeprazole (orally; positive-control), followed by oral
administration of 1mL of 60% ethanol plus 150mM HCl (inducer). In the chronic
study, rats were administered 10% diluted inducer in drinking water, and 0.6%
dextrin, 0.2% or 0.6% TCN, and 0.05% omeprazole were administered in chow for 4
weeks. Acid content, gastric structure, oxidative stress, and markers of
inflammation in the stomach tissue were measured at the end of experiment.
RESULTS: Acute and chronic ethanol/HCl administration caused the inner layer of
the stomach to redden, hemorrhage, and edema in the control group; TCN-H reduced
these symptoms more effectively than did the omeprazole positive-control. Acid
production and total acidity in the stomach increased in the control group, which
was markedly suppressed by omeprazole. TCN also reduced the acid production and
acidity, but not to the same degree as omeprazole. H-E and PAS staining revealed
that in the inner layer of the stomach, cellular structure was disrupted, with an
increased nuclear size and thickness, disarrangement, and decreased mucin in the
control group. TCN prevented the cellular disruption in the inner layer, and TCN
H was more effective than the positive-control. This was associated with
oxidative stress and inflammation. TCN dose-dependently reduced the infiltration
of mast cells and TNF-alpha expression in the inner layer of the stomach, and
decreased lipid peroxides by increasing superoxide dismutase and glutathione
peroxidase expression. CONCLUSIONS: TCN-H acutely and chronically protected
against gastritis and gastric ulcer by reducing oxidative stress and
inflammation, not by completely suppressing gastric acid production.
PMID- 28687508
TI - A framework for the targeted selection of herbs with similar efficacy by
exploiting drug repositioning technique and curated biomedical knowledge.
AB - ETHNO PHARMACOLOGICAL RELEVANCE: Plants have been the most important natural
resources for traditional medicine and for the modern pharmaceutical industry.
They have been in demand in regards to finding alternative medicinal herbs with
similar efficacy. Due to the very low probability of discovering useful compounds
by random screening, researchers have advocated for using targeted selection
approaches. Furthermore, because drug repositioning can speed up the process of
drug development, an integrated technique that exploits chemical, genetic, and
disease information has been recently developed. Building upon these findings, in
this paper, we propose a novel framework for the targeted selection of herbs with
similar efficacy by exploiting drug repositioning technique and curated modern
scientific biomedical knowledge, with the goal of improving the possibility of
inferring the traditional empirical ethno-pharmacological knowledge. MATERIALS
AND METHODS: To rank candidate herbs on the basis of similarities against target
herb, we proposed and evaluated a framework that is comprised of the following
four layers: links, extract, similarity, and model. In the framework, multiple
databases are linked to build an herb-compound-protein-disease network which was
composed of one tripartite network and two bipartite networks allowing
comprehensive and detailed information to be extracted. Further, various
similarity scores between herbs are calculated, and then prediction models are
trained and tested on the basis of theses similarity features. RESULTS: The
proposed framework has been found to be feasible in terms of link loss. Out of
the 50 similarities, the best one enhanced the performance of ranking herbs with
similar efficacy by about 120-320% compared with our previous study. Also, the
prediction model showed improved performance by about 180-480%. While building
the prediction model, we identified the compound information as being the most
important knowledge source and structural similarity as the most useful measure.
CONCLUSIONS: In the proposed framework, we took the knowledge of herbal medicine,
chemistry, biology, and medicine into consideration to rank herbs with similar
efficacy in candidates. The experimental results demonstrated that the
performances of framework outperformed the baselines and identified the important
knowledge source and useful similarity measure.
PMID- 28687509
TI - Postoperative Liver Failure Risk Score: Identifying Patients with Resectable
Perihilar Cholangiocarcinoma Who Can Benefit from Portal Vein Embolization.
AB - BACKGROUND: Major liver resection for perihilar cholangiocarcinoma (PHC) is
associated with a 22% to 33% postoperative liver failure incidence. The aim of
this study was analyze the predictive value of future liver remnant (FLR) volume
for postoperative liver failure after resection for PHC and to develop a risk
score to improve patient selection for portal vein embolization. STUDY DESIGN: A
consecutive series of 217 patients underwent major liver resection for PHC
between 1997 and 2014 at 2 Western centers; FLR volumes were calculated with CT
volumetry; other variables included jaundice at presentation, immediate
preoperative bilirubin, and preoperative cholangitis. The FLR volume was
categorized as <30%, 30% to 45%, or >45%. A risk score for postoperative liver
failure (grade B/C according to the International Study Group of Liver Surgery
criteria) was developed using multivariable logistic regression with 5 predefined
variables. RESULTS: Postoperative liver failure incidence was 24% and liver
failure-related mortality was 12%. Risk factors for liver failure were FLR volume
<30% (odds ratio 4.2; 95% CI 1.77 to 10.3) and FLR volume 30% to 45% (odds ratio
1.4; 95% CI 10.6 to 3.4). In addition, jaundice at presentation (odds ratio 3.1;
95% CI 1.1 to 9.0), immediate preoperative bilirubin >50 MUmol/L (>2.9 mg/dL)
(odds ratio 4.3; 95% CI 1.7 to 10.7), and preoperative cholangitis (odds ratio
3.4; 95% CI 1.6 to 7.4) were risk factors for liver failure. These variables were
included in a risk score that showed good discrimination (area under the curve
0.79; 95% CI 0.72 to 0.86) and ranking patients in 3 risk sub-groups with
predicted liver failure incidence of 4%, 14%, and 44%. CONCLUSIONS: The selection
of patients for portal vein embolization using only liver volume is insufficient,
considering the other predictors of liver failure in PHC patients. The proposed
risk score can be used for selection of patients for portal vein embolization,
for adequate patient counseling, and identification of other modifiable risk
factors besides liver volume.
PMID- 28687511
TI - First Lieutenant William T Fitzsimons, MD.
PMID- 28687510
TI - Flange Gastroenterostomy Results in Reduction in Delayed Gastric Emptying after
Standard Pancreaticoduodenectomy: A Prospective Cohort Study.
AB - BACKGROUND: Delayed gastric emptying (DGE) is a common serious problem after
pancreaticoduodenectomy (PD). Flange gastrojejunostomy (FL-GE) is a previously
described technique that creates an internal flange in a hand-sewn
gastroenterostomy. Results of FL-GE on incidence and severity of DGE after PD are
presented. STUDY DESIGN: Data were extracted from a prospective database of PD.
Standard PD with antrectomy were performed with flange gastroenterostomy (FL-GE)
or other techniques (NonFL-GE) at a single institution. The International Study
Group of Pancreatic Surgery (ISGPS) definition of DGE was used, and DGE severity
was graded based on the ISGPS grading system and the Modified Accordion Grading
System (MAGS). RESULTS: There were 215 standard PDs performed. Sixty-eight (32%)
were FL-GE and 147 (68%) were NonFL-GE. Delayed gastric emptying rates in FL-GE
and NonFL-GE were 9% and 23%, respectively (p = 0.012). Differences in severity
of DGE were even more prominent: 29% of DGEs in the NonFL-GE group were ISGPS
grade C vs 0% in FL-GE. Also, 35% of DGEs in the NonFL-GE group were MAGS 3 vs 0%
in FL-GE. Because of some differences in sex and inflammatory complications
between groups, a propensity score analysis was performed, creating 57 matched
patients in the FL-GE and NonFL-GE groups. The incidence of DGE remained
significantly different in the groups (5% in FL-GE vs 18% in NonFL-GE; p =
0.039). CONCLUSIONS: In this cohort study, the flange technique was associated
with a marked reduction in the incidence of DGE after PD.
PMID- 28687512
TI - Recessive mutation in EXOSC3 associates with mitochondrial dysfunction and
pontocerebellar hypoplasia.
AB - Recessive mutations in EXOSC3, encoding a subunit of the human RNA exosome
complex, cause pontocerebellar hypoplasia type 1b (PCH1B). We report a boy with
severe muscular hypotonia, psychomotor retardation, progressive microcephaly, and
cerebellar atrophy. Biochemical abnormalities comprised mitochondrial complex I
and pyruvate dehydrogenase complex (PDHc) deficiency. Whole exome sequencing
uncovered a known EXOSC3 mutation p.(D132A) as the underlying cause. In patient
fibroblasts, a large portion of the EXOSC3 protein was trapped in the cytosol.
MtDNA copy numbers in muscle were reduced to 35%, but mutations in the mtDNA and
in nuclear mitochondrial genes were ruled out. RNA-Seq of patient muscle showed
highly increased mRNA copy numbers, especially for genes encoding structural
subunits of OXPHOS complexes I, III, and IV, possibly due to reduced degradation
by a dysfunctional exosome complex. This is the first case of mitochondrial
dysfunction associated with an EXOSC3 mutation, which expands the phenotypic
spectrum of PCH1B. We discuss the links between exosome and mitochondrial
dysfunction.
PMID- 28687513
TI - CbbR and RegA regulate cbb operon transcription in Ralstonia eutropha H16.
AB - The biotechnologically important Gram-negative beta-proteobacterium Ralstonia
eutropha H16 is able to grow lithoautotrophically by utilizing CO2 and H2 as sole
carbon and energy sources, respectively. CO2 is fixed by the CBB cycle, which is
encoded in duplicate on the genome of R. eutropha H16. The transcription of both
cbb operons is controlled by the transcription regulator CbbR dependent on
intracellular PEP levels as a response to the carbon-state of the cell. As
demonstrated in this study transcription control of both cbb operons appears to
be more complex and additionally involves, next to CbbR, the transcription
regulator RegA as part of the global transcription regulation system RegA/RegB.
The identification of a highly conserved RegA/RegB homologue in R. eutropha H16
and experimental evidence gathered in this study reveal that RegA plays a crucial
role in the transcription control of both cbb promoters. RegA is able to induce
cbb promoter activity and controls transcription in combination with CbbR
dependent on cellular PEP concentrations. These results clearly demonstrate that
RegA plays an important role in cbb operon transcription regulation and may also
be relevant for the control of other energy-utilizing and energy-generating
pathways of R. eutropha H16. In addition to promoting a more complete
understanding of the CO2 fixation mechanism of R. eutropha H16 these findings
also provide crucial insights for the utilization of this bacterium in
biotechnological applications with respect to CO2 fixation.
PMID- 28687514
TI - Management and control of microbiologically influenced corrosion (MIC) in the oil
and gas industry-Overview and a North Sea case study.
AB - Microbiologically influenced corrosion (MIC) is the terminology applied where the
actions of microorganisms influence the corrosion process. In literature, terms
such as microbial corrosion, biocorrosion, microbially influenced/induced
corrosion, and biodegradation are often applied. MIC research in the oil and gas
industry has seen a revolution over the past decade, with the introduction of
molecular microbiological methods: (MMM) as well as new industry standards and
procedures of sampling biofilm and corrosion products from the process system.
This review aims to capture the most important trends the oil and gas industry
has seen regarding MIC research over the past decade. The paper starts out with
an overview of where in the process stream MIC occurs - from the oil reservoir to
the consumer. Both biotic and abiotic corrosion mechanisms are explained in the
context of managing MIC using a structured corrosion management (CM) approach.
The corrosion management approach employs the elements of a management system to
ensure that essential corrosion control activities are carried out in an
effective, sustainable, well-planned and properly executed manner. The 3-phase
corrosion management approach covering of both biotic and abiotic internal
corrosion mechanisms consists of 1) corrosion assessment, 2) corrosion mitigation
and 3) corrosion monitoring. Each of the three phases are described in detail
with links to recent field cases, methods, industry standards and sampling
protocols. In order to manage the corrosion threat, operators commonly use models
to support decision making. The models use qualitative, semi-quantitative or
quantitative measures to help assess the rate of degradation caused by MIC. The
paper reviews four existing models for MIC Threat Assessment and describe a new
model that links the threat of MIC in the oil processing system located on an
offshore platform with a Risk Based Inspection (RBI) approach. A recent field
case highlights and explains the conflicting historic results obtained through
serial dilution of culture media using the most probable number (MPN) method as
compared to data obtained from corrosion monitoring and the quantitative
polymerase chain reaction (qPCR) method. Results from qPCR application in the
field case have changed the way MIC is monitored on the oil production facility
in the North Sea. A number of high quality resources have been published as
technical conference papers, books, educational videos and peer-reviewed
scientific papers, and thus we end the review with an updated list of state-of
the-art resources for anyone desiring to become more familiar with the topic of
MIC in the upstream oil and gas sector.
PMID- 28687515
TI - Effect of a Pseudomonas fluorescens tailocin against phytopathogenic Xanthomonas
observed by atomic force microscopy.
AB - Phage tail-like bacteriocins, called tailocins, represent a class of protein
complexes produced by a multitude of bacteria. Pseudomonas fluorescens SF4c, a
strain isolated from wheat rhizosphere, produces a bacteriocin similar to phage
tail-like pyocins of Pseudomonas aeruginosa. This tailocin has antimicrobial
activity against several phytopathogenic strains of the genus Xanthomonas and
Pseudomonas. In this work, the effect of the SF4c tailocin on the phytopathogenic
strain X. axonopodis pv vesicatoria Xcv Bv5-4a was analyzed through Atomic Force
Microscopy (AFM). We demonstrated that tailocins adhere and cause damage to the
cell envelope of strain Xcv Bv5-4a. This results in a rapid leakage of
intracellular materials, with the subsequent decrease of cell volume. Finally,
lysis of sensitive bacteria occurs. This study provides, to our knowledge, the
first evidence about the effect of a tailocin analyzed by AFM. Further studies
are in progress to evaluate the use of SF4c tailocin in the biocontrol of
bacterial spot on tomato.
PMID- 28687516
TI - Reconstructing anatomy from electro-physiological data.
AB - Here we show how it is possible to make estimates of brain structure based on MEG
data. We do this by reconstructing functional estimates onto distorted cortical
manifolds parameterised in terms of their spherical harmonics. We demonstrate
that both empirical and simulated MEG data give rise to consistent and plausible
anatomical estimates. Importantly, the estimation of structure from MEG data can
be quantified in terms of millimetres from the true brain structure. We show, for
simulated data, that the functional assumptions which are closer to the
functional ground-truth give rise to anatomical estimates that are closer to the
true anatomy.
PMID- 28687518
TI - Neural inhibition can explain negative BOLD responses: A mechanistic modelling
and fMRI study.
AB - Functional magnetic resonance imaging (fMRI) of hemodynamic changes captured in
the blood oxygen level-dependent (BOLD) response contains information of brain
activity. The BOLD response is the result of a complex neurovascular coupling and
comes in at least two fundamentally different forms: a positive and a negative
deflection. Because of the complexity of the signaling, mathematical modelling
can provide vital help in the data analysis. For the positive BOLD response,
there are plenty of mathematical models, both physiological and phenomenological.
However, for the negative BOLD response, no physiologically based model exists.
Here, we expand our previously developed physiological model with the most
prominent mechanistic hypothesis for the negative BOLD response: the neural
inhibition hypothesis. The model was trained and tested on experimental data
containing both negative and positive BOLD responses from two studies: 1) a
visual-motor task and 2) a working-memory task in conjunction with administration
of the tranquilizer diazepam. Our model was able to predict independent
validation data not used for training and provides a mechanistic underpinning for
previously observed effects of diazepam. The new model moves our understanding of
the negative BOLD response from qualitative reasoning to a quantitative systems
biology level, which can be useful both in basic research and in clinical use.
PMID- 28687517
TI - Comparing test-retest reliability of dynamic functional connectivity methods.
AB - Due to the dynamic, condition-dependent nature of brain activity, interest in
estimating rapid functional connectivity (FC) changes that occur during resting
state functional magnetic resonance imaging (rs-fMRI) has recently soared.
However, studying dynamic FC is methodologically challenging, due to the low
signal-to-noise ratio of the blood oxygen level dependent (BOLD) signal in fMRI
and the massive number of data points generated during the analysis. Thus, it is
important to establish methods and summary measures that maximize reliability and
the utility of dynamic FC to provide insight into brain function. In this study,
we investigated the reliability of dynamic FC summary measures derived using
three commonly used estimation methods - sliding window (SW), tapered sliding
window (TSW), and dynamic conditional correlations (DCC) methods. We applied each
of these techniques to two publicly available rs-fMRI test-retest data sets - the
Multi-Modal MRI Reproducibility Resource (Kirby Data) and the Human Connectome
Project (HCP Data). The reliability of two categories of dynamic FC summary
measures were assessed, specifically basic summary statistics of the dynamic
correlations and summary measures derived from recurring whole-brain patterns of
FC ("brain states"). The results provide evidence that dynamic correlations are
reliably detected in both test-retest data sets, and the DCC method outperforms
SW methods in terms of the reliability of summary statistics. However, across all
estimation methods, reliability of the brain state-derived measures was low.
Notably, the results also show that the DCC-derived dynamic correlation variances
are significantly more reliable than those derived using the non-parametric
estimation methods. This is important, as the fluctuations of dynamic FC (i.e.,
its variance) has a strong potential to provide summary measures that can be used
to find meaningful individual differences in dynamic FC. We therefore conclude
that utilizing the variance of the dynamic connectivity is an important component
in any dynamic FC-derived summary measure.
PMID- 28687519
TI - Laminar fMRI: Applications for cognitive neuroscience.
AB - The cortex is a massively recurrent network, characterized by feedforward and
feedback connections between brain areas as well as lateral connections within an
area. Feedforward, horizontal and feedback responses largely activate separate
layers of a cortical unit, meaning they can be dissociated by lamina-resolved
neurophysiological techniques. Such techniques are invasive and are therefore
rarely used in humans. However, recent developments in high spatial resolution
fMRI allow for non-invasive, in vivo measurements of brain responses specific to
separate cortical layers. This provides an important opportunity to dissociate
between feedforward and feedback brain responses, and investigate communication
between brain areas at a more fine- grained level than previously possible in the
human species. In this review, we highlight recent studies that successfully used
laminar fMRI to isolate layer-specific feedback responses in human sensory
cortex. In addition, we review several areas of cognitive neuroscience that stand
to benefit from this new technological development, highlighting contemporary
hypotheses that yield testable predictions for laminar fMRI. We hope to encourage
researchers with the opportunity to embrace this development in fMRI research, as
we expect that many future advancements in our current understanding of human
brain function will be gained from measuring lamina-specific brain responses.
PMID- 28687520
TI - High channel count single-unit recordings from nonhuman primate frontal cortex.
AB - BACKGROUND: Single unit recording in behaving nonhuman primates is widely used to
study the primate central nervous system. However, certain questions cannot be
addressed without recording large numbers of neurons simultaneously. Multiple 96
electrode probes can be implanted at one time, but certain problems must be
overcome to make this approach practical. NEW METHOD: We describe a series of
innovations and practical guidance for implanting and recording from 8 arrays of
96 electrodes (768 electrodes) in the frontal cortex of Macaca mulatta. The
methods include an individualized 3D-printed connector mounting platform,
sequencing of assembly and surgical steps to minimize surgery time, and
interventions to protect electrical connections of the implant. RESULTS: The
methodology is robust and was successful in our hands on the first attempt. On
average, we were able to isolate hundreds (535.7 and 806.9 in two animals) of
high quality units in each session during one month of recording. COMPARISON WITH
EXISTING METHODS: To the best of our knowledge, this technique at least doubles
the number of Blackrock arrays that have been successfully implanted in single
animals. Although each technological component was pre-existing at the time we
developed these methods, their amalgamation to solve the problem of high channel
count recording is novel. CONCLUSIONS: The implantation of large numbers of
electrodes opens new research possibilities. Refinements could lead to even
greater capacity.
PMID- 28687521
TI - Simultaneous GCaMP6-based fiber photometry and fMRI in rats.
AB - BACKGROUND: Understanding the relationship between neural and vascular signals is
essential for interpretation of functional MRI (fMRI) results with respect to
underlying neuronal activity. Simultaneously measuring neural activity using
electrophysiology with fMRI has been highly valuable in elucidating the neural
basis of the blood oxygenation-level dependent (BOLD) signal. However, this
approach is also technically challenging due to the electromagnetic interference
that is observed in electrophysiological recordings during MRI scanning. NEW
METHOD: Recording optical correlates of neural activity, such as calcium signals,
avoids this issue, and has opened a new avenue to simultaneously acquire neural
and BOLD signals. RESULTS: The present study is the first to demonstrate the
feasibility of simultaneously and repeatedly acquiring calcium and BOLD signals
in animals using a genetically encoded calcium indicator, GCaMP6. This approach
was validated with a visual stimulation experiment, during which robust increases
of both calcium and BOLD signals in the superior colliculus were observed. In
addition, repeated measurement in the same animal demonstrated reproducible
calcium and BOLD responses to the same stimuli. COMPARISON WITH EXISTING
METHOD(S): Taken together, simultaneous GCaMP6-based fiber photometry and fMRI
recording presents a novel, artifact-free approach to simultaneously measuring
neural and fMRI signals. Furthermore, given the cell-type specificity of GCaMP6,
this approach has the potential to mechanistically dissect the contributions of
individual neuron populations to BOLD signal, and ultimately reveal its
underlying neural mechanisms. CONCLUSIONS: The current study established the
method for simultaneous GCaMP6-based fiber photometry and fMRI in rats.
PMID- 28687522
TI - Dimension reduction of frequency-based direct Granger causality measures on short
time series.
AB - BACKGROUND: The mainstream in the estimation of effective brain connectivity
relies on Granger causality measures in the frequency domain. If the measure is
meant to capture direct causal effects accounting for the presence of other
observed variables, as in multi-channel electroencephalograms (EEG), typically
the fit of a vector autoregressive (VAR) model on the multivariate time series is
required. For short time series of many variables, the estimation of VAR may not
be stable requiring dimension reduction resulting in restricted or sparse VAR
models. NEW METHOD: The restricted VAR obtained by the modified backward-in-time
selection method (mBTS) is adapted to the generalized partial directed coherence
(GPDC), termed restricted GPDC (RGPDC). Dimension reduction on other frequency
based measures, such the direct directed transfer function (dDTF), is
straightforward. RESULTS: First, a simulation study using linear stochastic
multivariate systems is conducted and RGPDC is favorably compared to GPDC on
short time series in terms of sensitivity and specificity. Then the two measures
are tested for their ability to detect changes in brain connectivity during an
epileptiform discharge (ED) from multi-channel scalp EEG. COMPARISON WITH
EXISTING METHOD(S): It is shown that RGPDC identifies better than GPDC the
connectivity structure of the simulated systems, as well as changes in the brain
connectivity, and is less dependent on the free parameter of VAR order.
CONCLUSIONS: The proposed dimension reduction in frequency measures based on VAR
constitutes an appropriate strategy to estimate reliably brain networks within
short-time windows.
PMID- 28687524
TI - Pierpont syndrome associated with the p.Tyr446Cys missense mutation in TBL1XR1.
AB - We present a 7-year old male with severe delays, hypotonia and dysmorphic
features who had striking, deep palmar and plantar creases and pillowing of the
soft tissues of the palms and soles. His facial features included a high anterior
hairline, small eyes with narrowed palpebral fissures, a bulbous nasal tip with a
short columella, and a large mouth with a thin upper vermilion, and small chin.
He had a submucous cleft palate, bilateral cryptorchidism and hydronephrosis.
Cranial imaging demonstrated an Arnold Chiari malformation that was also present
in his maternal uncle by report. Exome sequencing revealed a de novo heterozygous
sequence variant, p.Tyr446Cys, in TBL1XR1 that has previously been reported in
six patients with Pierpont syndrome. This sequence variant occurs in the carboxy
terminal, WD40 domain of the protein. As TBL1XR1 is a critical component of the
NCoR/SMRT co-repressor complex and the WD40 repeats are hypothesized to interact
with histone H2B and H4, the mutation may impact protein interactions necessary
for stabilizing the complex with chromatin. De novo missense and frameshift
mutations and deletions involving TBL1XR1 have been described in patients with
intellectual disability and autism, but without any of the dysmorphic findings or
malformations associated with Pierpont syndrome, implying a mutation-specific
mechanism for the pathogenicity of p.Tyr446Cys. Our case is the first individual
with this mutation to have a submucous cleft palate and hydronephrosis, although
his severe delays, hypotonia, dysmorphic findings and emerging scoliosis appear
consistent with previous reports. His distinctive facial and digital features are
further evidence that p.Tyr446Cys results in a clinically recognizable, syndromic
form of intellectual disability in contrast to other TBL1XR1 mutations.
PMID- 28687523
TI - TDP-43 in the spectrum of MND-FTLD pathologies.
AB - The relationship between RNA-binding proteins, particularly TAR DNA binding
protein 43 (TDP-43), and neurodegeneration is an important area of research. TDP
43 is involved in so many cellular processes that perturbation of protein
homeostasis can lead to countless downstream effects. Understanding what leads to
this disease-related protein imbalance and the resulting cellular and molecular
effects will help to develop targets for disease intervention, whether it be
prevention of protein accumulation, or addressing a secondary effect of protein
accumulation. Here we review the current literature of TDP-43 and TDP-43
pathologies, the effects of TDP-43 overexpression and disruption of synaptic
proteins through its binding of messenger RNA, leading to synaptic dysfunction.
This review highlights some of the still-limited knowledge of the protein TDP-43
and how it can contribute to disease.
PMID- 28687525
TI - SMD Kozlowski type caused by p.Arg594His substitution in TRPV4 reveals abnormal
ossification and notochordal remnants in discs and vertebrae.
AB - Spondylometaphyseal dysplasia Kozlowski type (SMDK) is a monogenic disorder
within the TRPV4 dysplasia spectrum and has characteristic spinal and metaphyseal
changes. We report skeletal MR imaging in a two-year-old patient who manifested
typical clinical and radiographic features of SMDK. The diagnosis was confirmed
by molecular analysis which revealed a mutation NM_021625.4:c.1781G > A -
p.(Arg594His) in exon 11 of the TRPV4 gene. We have documented abnormalities in
endochondral formation of the long and short tubular bones as well as round bones
of the wrists and feet. The vertebral bodies had increased thickness of hyaline
cartilage which enveloped ossification centers. The vertebrae and discs also had
abnormalities in size, shape and structure. These anomalies were most likely the
consequence of notochordal remnants presence within the intervertebral discs and
in the vertebral bodies. The advantages of MR imaging in bone dysplasias caused
by TRPV4 mutations are emphasized in this article.
PMID- 28687526
TI - First de novo ANK3 nonsense mutation in a boy with intellectual disability,
speech impairment and autistic features.
AB - Ankyrin-G, encoded by ANK3, plays an important role in neurodevelopment and
neuronal function. There are multiple isoforms of Ankyrin-G resulting in
differential tissue expression and function. Heterozygous missense mutations in
ANK3 have been associated with autism spectrum disorder. Further, in three
siblings a homozygous frameshift mutation affecting only the longest isoform and
a patient with a balanced translocation disrupting all isoforms were documented.
The latter four patients were affected by a variable degree of intellectual
disability, attention deficit hyperactivity disorder and autism. Here, we report
on a boy with speech impairment, intellectual disability, autistic features,
macrocephaly, macrosomia, chronic hunger and an altered sleeping pattern. By trio
whole-exome sequencing, we identified the first de novo nonsense mutation
affecting all ANK3 transcripts. Thus, our data expand the phenotype of ANK3
associated diseases and suggest an isoform-based, phenotypic continuum between
dominant and recessive ANK3-associated pathologies.
PMID- 28687527
TI - The first patient with sporadic X-linked intellectual disability with de novo
ZDHHC9 mutation identified by targeted next-generation sequencing.
AB - X-linked intellectual disability (XLID) is a genetically heterogeneous disorder
involving more than 100 genes known to date. Here, we describe a Korean male
infant with global developmental delay. He had neither facial dysmorphism nor
skeletal abnormalities. Bayley scale of infant and toddler development third
edition (Bayley-III) measured at age of 2 years revealed marked global
developmental delays without Marfanoid habitus, structural brain abnormalities,
or epilepsy. The patient's cognitive, motor, and language developmental ages were
8-9 months, 12 months, and 9 months, respectively. Targeted next-generation
sequencing revealed a de novo mutation [NM_001008222.2(ZDHHC9): c.286C > T
(p.(Arg96Trp))] in the affected patient. This mutation has been reported
previously in a family XLID with Marfanoid features. Sanger sequencing analysis
of the proband and his parents revealed that the missense mutation was present in
the proband only (absent in his parents). This indicates that the mutation is de
novo in origin. To the best of our knowledge, this is the first report describing
sporadic XLID with de novo ZDHHC9 mutation identified by targeted next-generation
sequencing.
PMID- 28687528
TI - Selection of effective cocrystals former for dissolution rate improvement of
active pharmaceutical ingredients based on lipoaffinity index.
AB - New theoretical screening procedure was proposed for appropriate selection of
potential cocrystal formers possessing the ability of enhancing dissolution rates
of drugs. The procedure relies on the training set comprising 102 positive and 17
negative cases of cocrystals found in the literature. Despite the fact that the
only available data were of qualitative character, performed statistical analysis
using binary classification allowed to formulate quantitative criterions. Among
considered 3679 molecular descriptors the relative value of lipoaffinity index,
expressed as the difference between values calculated for active compound and
excipient, has been found as the most appropriate measure suited for
discrimination of positive and negative cases. Assuming 5% precision, the applied
classification criterion led to inclusion of 70% positive cases in the final
prediction. Since lipoaffinity index is a molecular descriptor computed using
only 2D information about a chemical structure, its estimation is straightforward
and computationally inexpensive. The inclusion of an additional criterion
quantifying the cocrystallization probability leads to the following conjunction
criterions Hmix<-0.18 and DeltaLA>3.61, allowing for identification of
dissolution rate enhancers. The screening procedure was applied for finding the
most promising coformers of such drugs as Iloperidone, Ritonavir, Carbamazepine
and Enthenzamide.
PMID- 28687529
TI - Design, synthesis, and biological evaluation of 2,4-dihydropyrano[2,3-c]pyrazole
derivatives as autotaxin inhibitors.
AB - Inhibition of Autotaxin (ATX) is a potential treatment strategy for several
diseases, including tumors with elevated ATX-lysophosphatidic acid (LPA)
signaling. Combining structure-based virtual screening together with hen egg
white Autotaxin (ewATX) activity assays enabled the discovery of novel small
molecule ATX inhibitors with a 2,4-dihydropyrano[2,3-c]pyrazole scaffold. These
compounds are suggested to bind to the lipophilic pocket, leaving the active site
unrestrained. Our most potent compound, (S)-6-amino-4-(3,4-dichlorophenyl)-3-(4
[(4-fluorobenzyl)oxy]phenyl)-2,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile [(S)
25], inhibited human ATX (hATX) with an IC50-value of 134nM. It also blocked ATX
evoked but not LPA-mediated A2058 melanoma cell migration. Noteworthy, molecular
modeling correctly predicted the biologically active enantiomer of 2,4
dihydropyrano[2,3-c]pyrazoles, as verified by compound crystallization and
activity assays. Our study established the ewATX activity assay as a valid and
affordable tool in ATX inhibitor discovery. Overall, our study offers novel
insights and approaches into design of novel ATX inhibitors targeting the
hydrophobic pocket instead of the active site.
PMID- 28687530
TI - Comparison of segmental-dependent permeability in human and in situ perfusion
model in rat.
AB - Nowadays, alternative methods have been developed to predict intestinal
permeability values in human as in vitro, in situ or ex vivo methods. They were
developed by the necessity to avoid the problems of the human permeability
experiments. However, determination of human permeability is needed to properly
validate the alternative methods. For this reason, recently, Dahlgren et al.
published an indirect method based on a deconvolution technique to estimate the
human permeability in different gastrointestinal segments (jejunum, ileum and
colon). Therefore, the objective of this research was to demonstrate that
Doluisio technique is a useful method to predict the human permeability in
different gastrointestinal segments. To achieve this goal, the rat permeability
in different segments, of the same drugs studied by Dahlgren et al. (atenolol,
metoprolol and ketoprofen), have been compared with the human data obtained by
the deconvolution method. The results obtained in this work show that the
Doluisio method is a reliable tool to predict segmental human permeability.
Consequently, the deconvolution method can be employed to build an extensive
database of human permeability, overall from ileum and colon, because there is a
lack of human permeability data of these distal segments. Once there are enough
human data available, the Doluisio technique will be a valuable alternative
method to predict the permeability of new molecules with therapeutic activity
without the requirement of human experiments.
PMID- 28687531
TI - Informing the Development of a Mobile Phone HIV Testing Intervention: Intentions
to Use Specific HIV Testing Approaches Among Young Black Transgender Women and
Men Who Have Sex With Men.
AB - BACKGROUND: Regular human immunodeficiency virus (HIV) testing of persons at risk
is critical to HIV prevention. Infrequent HIV testing and late diagnosis of HIV
infection have been observed among young black men who have sex with men (MSM)
and transwomen (transgender women)-two groups overrepresented in the HIV
epidemic. OBJECTIVE: The objective of this study was to inform the development of
a brief mobile phone intervention to increase HIV testing among young black MSM
and transwomen by providing a tailored recommendation of an optimal HIV testing
approach. We identified demographic, behavioral, psychosocial, and
sociostructural factors associated with intentions to use three specific HIV
testing approaches: self-testing, testing at a clinic or other provider, and
couples HIV testing and counseling (CHTC). METHODS: Individuals were eligible for
a Web-based survey if they were male at birth; were between the ages of 16 and 29
years; self-identified as black, African American, Caribbean black, African
black, or multiethnic black; were not known to be HIV-infected; and reported
insertive or receptive anal intercourse with a man or transwoman in the last 12
months. Recruitment occurred via banner advertisements placed on a range of
social and sexual networking websites and apps in New York City and nationally,
and via events attended by young black MSM and transwomen in New York City.
Intention to test by each testing method was analyzed using logistic regression
with best subset models and stepwise variable selection. RESULTS: Among 169
participants, intention to use a self-test was positively associated with comfort
in testing by a friend or a partner at home (Adjusted odds ratio, AOR, 2.40; 95%
CI 1.09-5.30), and stigma or fear as a reason not to test (AOR 8.61; 95% CI 2.50
29.68) and negatively associated with higher social support (AOR 0.48; 95% CI
0.33-0.72) and having health insurance (AOR 0.21; 95% CI 0.09-0.54). Intention to
test at a clinic or other provider was positively associated with self-efficacy
for HIV testing (AOR 2.87; 95% CI 1.48-5.59) and social support (AOR 1.98; 95% CI
1.34-2.92), and negatively associated with a lifetime history of incarceration
(AOR 0.37; 95% CI 0.16-0.89). Intention to test by CHTC was negatively associated
with higher educational level (Some college or Associate's degree vs high school
graduate or less [AOR 0.81; 95% CI 0.39-1.70]; Bachelor's degree or more vs high
school graduate or less [AOR 0.28; 95% CI 0.11-0.70]). CONCLUSIONS: Unique
factors were associated with intention to test using specific testing approaches.
These data will be critical for the development of a tailored intervention that
shows promise to increase comfort and experiences with a variety of testing
approaches among young black MSM and transwomen.
PMID- 28687532
TI - Studying Scale-Up and Spread as Social Practice: Theoretical Introduction and
Empirical Case Study.
AB - BACKGROUND: Health and care technologies often succeed on a small scale but fail
to achieve widespread use (scale-up) or become routine practice in other settings
(spread). One reason for this is under-theorization of the process of scale-up
and spread, for which a potentially fruitful theoretical approach is to consider
the adoption and use of technologies as social practices. OBJECTIVE: This study
aimed to use an in-depth case study of assisted living to explore the feasibility
and usefulness of a social practice approach to explaining the scale-up of an
assisted-living technology across a local system of health and social care.
METHODS: This was an individual case study of the implementation of a Global
Positioning System (GPS) "geo-fence" for a person living with dementia, nested in
a much wider program of ethnographic research and organizational case study of
technology implementation across health and social care (Studies in Co-creating
Assisted Living Solutions [SCALS] in the United Kingdom). A layered sociological
analysis included micro-level data on the index case, meso-level data on the
organization, and macro-level data on the wider social, technological, economic,
and political context. Data (interviews, ethnographic notes, and documents) were
analyzed and synthesized using structuration theory. RESULTS: A social practice
lens enabled the uptake of the GPS technology to be studied in the context of
what human actors found salient, meaningful, ethical, legal, materially possible,
and professionally or culturally appropriate in particular social situations.
Data extracts were used to illustrate three exemplar findings. First,
professional practice is (and probably always will be) oriented not to
"implementing technologies" but to providing excellent, ethical care to sick and
vulnerable individuals. Second, in order to "work," health and care technologies
rely heavily on human relationships and situated knowledge. Third, such
technologies do not just need to be adopted by individuals; they need to be
incorporated into personal habits and collaborative routines (both lay and
professional). CONCLUSIONS: Health and care technologies need to be embedded
within sociotechnical networks and made to work through situated knowledge,
personal habits, and collaborative routines. A technology that "works" for one
individual in a particular set of circumstances is unlikely to work in the same
way for another in a different set of circumstances. We recommend the further
study of social practices and the application of co-design principles. However,
our findings suggest that even if this occurs, the scale-up and spread of many
health and care technologies will be neither rapid nor smooth.
PMID- 28687534
TI - Over half of anaesthetic trainees have had car crash or near miss after night
shift, survey finds.
PMID- 28687533
TI - Mobile Health Technology Using a Wearable Sensorband for Female College Students
With Problem Drinking: An Acceptability and Feasibility Study.
AB - BACKGROUND: An increasing number of mobile app interventions have been developed
for problem drinking among college students; however, few studies have examined
the integration of a mobile app with continuous physiological monitoring and
alerting of affective states related to drinking behaviors. OBJECTIVE: The aim of
this paper was to evaluate the acceptability and feasibility of Mind the Moment
(MtM), a theoretically based intervention for female college students with
problem drinking that combines brief, in-person counseling with ecological
momentary intervention (EMI) on a mobile app integrated with a wearable
sensorband. METHODS: We recruited 10 non-treatment seeking, female undergraduates
from a university health clinic who scored a 3 or higher on the Alcohol Use
Disorders Identification Test-Consumption (AUDIT-C) to participate in this pilot
study. Study activities involved an in-person baseline intake and 1 follow-up
assessment, 2 in-person alcohol brief intervention counseling sessions, and use
of MtM technology components (sensorband and EMI on a mobile app) for
approximately 3-4 weeks. The intervention used motivational interviewing (MI) and
cognitive behavioral therapy (CBT) strategies for reducing risks associated with
drinking. We used both qualitative and quantitative assessments to measure
acceptability of the intervention and feasibility of delivery. Use patterns of
the sensorband and mobile app were also collected. RESULTS: Quantitative and
qualitative data indicated high levels of acceptability for the MtM intervention.
Altogether, participants made reports on the app on 26.7% (78/292) the days the
technology was available to them and completed a total of 325 reports with wide
variation between participants. Qualitative findings indicated that sensorband
elicited alerts promoted an increase in awareness of thoughts, feelings, and
behaviors related to current environmental stressors and drinking behaviors in
theoretically meaningful ways. Specific challenges related to functionality and
form of the sensorband were identified. CONCLUSIONS: Delivering intervention
material "just-in-time," at the moment participants need to use behavioral
strategies has great potential to individualize behavioral interventions for
reducing problem drinking and other health behaviors. These findings provide
initial evidence for the promise of wearable sensors for increasing potency of
theoretically grounded mobile health interventions and point to directions for
future research and uptake of these technologies.
PMID- 28687536
TI - What makes an essential medicine? WHO's new list focuses on antibiotic
resistance, adds expensive drugs, and downgrades Tamiflu.
PMID- 28687537
TI - Rape survivor is sentenced to 30 years in jail under El Salvador's extreme anti
abortion law.
PMID- 28687535
TI - Endothelial NF-kappaB Blockade Abrogates ANCA-Induced GN.
AB - ANCA-associated vasculitis (AAV) is a highly inflammatory condition in which ANCA
activated neutrophils interact with the endothelium, resulting in necrotizing
vasculitis. We tested the hypothesis that endothelial NF-kappaB mediates
necrotizing crescentic GN (NCGN) and provides a specific treatment target.
Reanalysis of kidneys from previously examined murine NCGN disease models
revealed NF-kappaB activation in affected kidneys, mostly as a p50/p65
heterodimer, and increased renal expression of NF-kappaB-dependent tumor necrosis
factor alpha (TNF-alpha). NF-kappaB activation positively correlated with
crescent formation, and nuclear phospho-p65 staining showed NF-kappaB activation
within CD31-expressing endothelial cells (ECs) in affected glomeruli. Therefore,
we studied the effect of ANCA on NF-kappaB activation in neutrophil/EC cocultures
in vitro ANCA did not activate NF-kappaB in primed human neutrophils, but ANCA
stimulated primed neutrophils activated NF-kappaB in ECs, at least in part via
TNF-alpha release. This effect increased endothelial gene transcription and
protein production of NF-kappaB-regulated interleukin-8. Moreover, upregulation
of endothelial NF-kappaB promoted neutrophil adhesion to EC monolayers, an effect
that was inhibited by a specific IKKbeta inhibitor. In a murine NCGN model,
prophylactic application of E-selectin-targeted immunoliposomes packed with p65
siRNA to downregulate endothelial NF-kappaB significantly reduced urine
abnormalities, renal myeloid cell influx, and NCGN. Increased glomerular
endothelial phospho-p65 staining in patients with AAV indicated that NF-kappaB is
activated in human NCGN also. We suggest that ANCA-stimulated neutrophils
activate endothelial NF-kappaB, which contributes to NCGN and provides a
potential therapeutic target in AAV.
PMID- 28687538
TI - Temporal Trends of Single-Photon Emission Computed Tomography Myocardial
Perfusion Imaging in Patients With Coronary Artery Disease: A 22-Year Experience
From a Tertiary Academic Medical Center.
AB - BACKGROUND: There has been a gradual decline in the prevalence of abnormal stress
single-photon emission computed tomography (SPECT) myocardial perfusion imaging
studies among patients without history of coronary artery disease (CAD). The
trends of SPECT studies among patients with known CAD have not been evaluated
previously. METHODS AND RESULTS: We assessed the Mayo Clinic nuclear cardiology
database for all stress SPECT tests performed between January 1991 and December
2012 in patients with history of CAD defined as having previous myocardial
infarction, percutaneous coronary intervention, and coronary artery bypass
grafting. The study cohort was divided into 5 time periods: 1991 to 1995, 1996 to
2000, 2001 to 2005, 2006 to 2010, and 2011 to 2012. There were 19 373 patients
with a history of CAD who underwent SPECT between 1991 and 2012 (mean age, 66.2+/
10.9 years; 75.4% men). Annual utilization of SPECT in these patients increased
from an average of 495 tests per year in 1991 to 1995 to 1425 in 2003 and then
decreased to 552 tests in 2012 without evidence for substitution with other
stress modalities. Asymptomatic patients initially increased until 2006 and then
decreased. Patients with typical angina decreased, whereas patients with dyspnea
and atypical angina increased. High-risk SPECT tests significantly decreased, and
the percentage of low-risk SPECT tests increased despite decreased SPECT
utilization between 2003 and 2012. Almost 80% of all tests performed in 2012 had
a low-risk summed stress score compared with 29% in 1991 (P<0.001). CONCLUSIONS:
In Mayo Clinic, Rochester, annual SPECT utilization in patients with previous CAD
increased between 1992 and 2003, but then decreased after 2003. High-risk SPECT
tests declined, whereas low-risk tests increased markedly. Our results suggest
that among patients with a history of CAD, SPECT was being increasingly utilized
in patients with milder CAD. This trend parallels reduced utilization of other
stress modalities, coronary angiography, reduced smoking, and greater utilization
of optimal medical therapy for prevention and treatment of CAD.
PMID- 28687540
TI - How Should We Interpret the Decrease in Annual Volume of Stress Imaging Tests for
Evaluation of Suspected or Known Coronary Artery Disease With Fewer High-Risk
Test Results?
PMID- 28687539
TI - Visual and Quantitative Assessment of Coronary Stenoses at Angiography Versus
Fractional Flow Reserve: The Impact of Risk Factors.
AB - BACKGROUND: The correlation between angiographic assessment of coronary stenoses
and fractional flow reserve (FFR) is weak. Whether and how risk factors impact
the diagnostic accuracy of angiography is unknown. We sought to evaluate the
diagnostic accuracy of angiography by visual estimate and by quantitative
coronary angiography when compared with FFR and evaluate the influence of risk
factors (RF) on this accuracy. METHODS AND RESULTS: In 1382 coronary stenoses
(1104 patients), percent diameter stenosis by visual estimation (DSVE) and by
quantitative coronary angiography (DSQCA) was compared with FFR. Patients were
divided into 4 subgroups, according to the presence of RFs, and the relationship
between DSVE, DSQCA, and FFR was analyzed. Overall, DSVE was significantly higher
than DSQCA (P<0.0001); nonetheless, when examined by strata of DS, DSVE was
significantly smaller than DSQCA in mild stenoses, although the reverse held true
for severe stenoses. Compared with FFR, a large scatter was observed for both
DSVE and DSQCA. When using a dichotomous FFR value of 0.80, C statistic was
significantly higher for DSVE than for DSQCA (0.712 versus 0.640, respectively;
P<0.001). C statistics for DSVE decreased progressively as RFs accumulated (0.776
for <=1 RF, 0.750 for 2 RFs, 0.713 for 3 RFs and 0.627 for >=4 RFs; P=0.0053). In
addition, in diabetics, the relationship between FFR and angiographic indices was
particularly weak (C statistics: 0.524 for DSVE and 0.511 for DSQCA).
CONCLUSIONS: Overall, DSVE has a better diagnostic accuracy than DSQCA to predict
the functional significance of coronary stenosis. The predictive accuracy of
angiography is moderate in patients with <=1 RFs, but weakens as RFs accumulate,
especially in diabetics.
PMID- 28687541
TI - Clues to Discordance and Dissimilarity Between Coronary Stenosis and Lesion
Specific Ischemia.
PMID- 28687542
TI - Skeletal Muscle Microvascular-Linked Improvements in Glycemic Control From
Resistance Training in Individuals With Type 2 Diabetes.
AB - OBJECTIVE: Insulin increases glucose disposal in part by enhancing microvascular
blood flow (MBF) and substrate delivery to myocytes. Insulin's microvascular
action is impaired with insulin resistance and type 2 diabetes. Resistance
training (RT) improves glycemic control and insulin sensitivity, but whether this
improvement is linked to augmented skeletal muscle microvascular responses in
type 2 diabetes is unknown. RESEARCH DESIGN AND METHODS: Seventeen (11 male and 6
female; 52 +/- 2 years old) sedentary patients with type 2 diabetes underwent 6
weeks of whole-body RT. Before and after RT, participants who fasted overnight
had clinical chemistries measured (lipids, glucose, HbA1c, insulin, and advanced
glycation end products) and underwent an oral glucose challenge (OGC) (50 g * 2
h). Forearm muscle MBF was assessed by contrast-enhanced ultrasound, skin MBF by
laser Doppler flowmetry, and brachial artery flow by Doppler ultrasound at
baseline and 60 min post-OGC. A whole-body DEXA scan before and after RT assessed
body composition. RESULTS: After RT, muscle MBF response to the OGC increased,
while skin microvascular responses were unchanged. These microvascular
adaptations were accompanied by improved glycemic control (fasting blood glucose,
HbA1c, and glucose area under the curve [AUC] during OGC) and increased lean body
mass and reductions in fasting plasma triglyceride, total cholesterol, advanced
glycation end products, and total body fat. Changes in muscle MBF response after
RT significantly correlated with reductions in fasting blood glucose, HbA1c, and
OGC AUC with adjustment for age, sex, % body fat, and % lean mass. CONCLUSIONS:
RT improves OGC-stimulated muscle MBF and glycemic control concomitantly,
suggesting that MBF plays a role in improved glycemic control from RT.
PMID- 28687543
TI - Injury epidemiology of tennis players at the 2011-2016 Australian Open Grand
Slam.
AB - AIM: To examine the epidemiology and in-event treatment frequency of injury at
the 2011-2016 Australian Open tournaments. METHODS: Injury incidence was defined
as a medical consultation by a tournament physician and in-event treatment
frequency as the mean total number of follow-up medical/physiotherapy
consultations (2013-2016 tournaments only). Data were collated by sex, injury
region and type and reported as frequencies per 10 000 game exposures. Incidence
rate s+/- 95% CI and rate ratios were used to test effects for injury, sex and
year. RESULTS: Female players experienced more injuries than male players (201.7
vs 148.6). The shoulder (5.1+/-1.1 injuries per year), foot (3.2+/-1.1), wrist
(3.1+/-1.5) and knee (3.1+/-1.1) were the most commonly injured regions among
females. Knee (3.5+/-1.6), ankle (2.3+/-1.3) and thigh (2.3+/-1.5) were the most
prevalent male injuries. Upper arm injuries and in-event treatment frequency
increased by >=2.4 times in both sexes over the 5-year period. Muscle injuries
were most frequent. There was a greater than twofold increase in men and women
with stress fractures over the 5-year period. The torso region, including the
neck, thoracic spine, trunk and abdominal, lumbar spine, hip and groin,
pelvis/buttock, attracted high in-event treatment frequencies in both sexes.
CONCLUSION: Investigation of injury at the Australian Open suggests that females
are more commonly injured than males. Upper and lower extremity injuries affected
females while lower limb injuries were more prominent in males. There was an
increasing rate of in-event treatments of upper limb and torso injuries as well
as stress fractures during the observation period.
PMID- 28687545
TI - New drugs and dosage forms.
PMID- 28687544
TI - Congressional action on rising drug prices remains a possibility.
PMID- 28687546
TI - Site-independent indication widens targets for immunotherapy product.
PMID- 28687547
TI - CMS paves way for pharmacists to help blunt metabolic effects of antipsychotics.
PMID- 28687549
TI - Implementation of a direct oral anticoagulant discharge service.
PMID- 28687550
TI - Sofosbuvir-velpatasvir: A single-tablet treatment for hepatitis C infection of
all genotypes.
AB - PURPOSE: The pharmacology, pharmacokinetics, interaction potential, efficacy, and
safety of the newest direct-acting antiviral (DAA) medication for the treatment
of chronic hepatitis C are reviewed. SUMMARY: Nonstructural proteins 5A (NS5A)
and 5B (NS5B) are key drivers of hepatitis C virus (HCV) replication.
Velpatasvir, an inhibitor of NS5A, was coformulated with the NS5B inhibitor
sofosbuvir to provide a single-tablet combination DAA (Epclusa, Gilead Sciences).
Sofosbuvir-velpatasvir was shown to have excellent activity against the 6 most
prevalent HCV genotypes in the United States, with reported rates of sustained
virological response at 12 weeks after treatment completion ranging from 95% to
100% in various HCV-infected populations, including patients with compensated
cirrhosis and prior treatment failures. In patients with decompensated cirrhosis
or HIV coinfection, reported cure rates are 85-100% and 92-100%, respectively.
The duration of treatment with sofosbuvir-velpatasvir is 12 weeks regardless of
the HCV genotype involved, previous treatment, and the presence of cirrhosis or
baseline resistance-associated NS5A mutations. In patients with decompensated
cirrhosis, sofosbuvir-velpatasvir must be used in combination with ribavirin.
Sofosbuvir-velpatasvir was well tolerated in clinical trials; adverse effects
reported at a rate of >=10% were fatigue, headache, nausea, and nasopharyngitis.
CONCLUSION: Sofosbuvir-velpatasvir is a DAA and the first single-tablet regimen
to treat HCV infection caused by all genotypes. The efficacy and tolerability of
sofosbuvir-velpatasvir have been observed in patients with types of HCV infection
that traditionally have been difficult to treat.
PMID- 28687551
TI - Nebulized opioids for the palliation of dyspnea in terminally ill patients.
AB - PURPOSE: The use of nebulized opioids for the palliation of dyspnea in terminally
ill patients is reviewed. SUMMARY: More than 50% of patients with advanced
diseases experience dyspnea during their final stages of life. Systemically
administered opioids are recommended for the management of dyspnea in these
patients, but adverse effects may limit their use. Nebulization offers an
alternative route for administering opioids, providing relief of dyspnea while
minimizing adverse events. An extensive literature search was conducted to
identify publications evaluating nebulized opioids for the palliation of dyspnea
in patients at end-of-life. Ten studies that evaluated nebulized morphine,
fentanyl, hydromorphone, and morphine-6-glucuronide were reviewed; 1 of these
studies evaluated 4 different opioids. Of these 10 studies, 2 had double-blind,
placebo-controlled, randomized crossover designs; 1 was retrospective, and the
remaining 7 were prospective studies. A total of 181 patients, all adults, were
evaluated. Subjective improvement in dyspnea from baseline was observed in 9 of
the 10 studies. Nebulized morphine 20 mg every 4 hours was the most common opioid
studied. Other doses of nebulized opioids included fentanyl 25 and 100 MUg and
hydromorphone 5 mg. Nine studies reported subjective improvement of dyspnea from
baseline after administering nebulized opioids. Six studies evaluated objective
outcomes and showed decreased respiratory rate (morphine, fentanyl, and
hydromorphone) and heart rate (hydromorphone) and increased oxygen saturation
(fentanyl). Mild-to-moderate adverse effects such as claustrophobia due to
nebulizer mask, drowsiness, cough, and bitter taste were described. CONCLUSION:
Nebulized opioids may provide subjective relief of dyspnea in terminally ill
patients with mild-to-moderate adverse effects.
PMID- 28687552
TI - Hyponatremia induced by hyperinsulinemia-euglycemia therapy.
AB - PURPOSE: A case of symptomatic hyponatremia induced by hyperinsulinemia
euglycemia (HIE) therapy is reported. SUMMARY: A 59-year-old, 81.65-kg woman with
hypertension, major depressive disorder, and anxiety arrived at a tertiary
medical center 1.5 hours after an intentional overdose of oral amlodipine 200 mg,
metoprolol tartrate 2,000 mg, and isosorbide mononitrate 1,200 mg. Upon arrival,
her pulse was 63 beats/min and blood pressure was 106/56 mm Hg. The patient's
blood pressure was refractory to fluids, calcium gluconate, and norepinephrine,
resulting in initiation of HIE therapy. She had recurrent episodes of
hypoglycemia, which required increases of the dextrose infusion and resulted in
the patient receiving a total of 6.9 L of dextrose with free water. Seventeen
hours into the hospitalization, the patient became obtunded due to hyponatremia
(serum sodium concentration, 121 mmol/L). HIE therapy was discontinued, an
infusion of 5% dextrose injection with sodium bicarbonate added was started, and
a bolus of 3% sodium chloride was administered. Nine hours after the presentation
of hyponatremia, the patient's serum sodium concentration normalized (137
mmol/L), and her symptoms resolved. The patient's blood pressure, pulse, and
mental status continued to improve, and the patient was transferred out of the
medical intensive care unit 41 hours after her arrival at the hospital.
CONCLUSION: A woman who overdosed on amlodipine, metoprolol tartrate, and
isosorbide mononitrate was treated with HIE therapy and developed symptomatic
hyponatremia. Hyponatremia resolved after administration of dextrose with sodium
bicarbonate infusion and 3% sodium chloride infusion and cessation of HIE
therapy.
PMID- 28687553
TI - Development of a pharmacy resident rotation to expand decentralized clinical
pharmacy services.
AB - PURPOSE: The development of a pharmacy resident rotation to expand decentralized
clinical pharmacy services is described. SUMMARY: In an effort to align with the
initiatives proposed within the ASHP Practice Advancement Initiative, the
department of pharmacy at Cleveland Clinic, a 1,400-bed academic, tertiary acute
care medical center in Cleveland, Ohio, established a goal to provide
decentralized clinical pharmacy services for 100% of patient care units within
the hospital. Patient care units that previously had no decentralized pharmacy
services were evaluated to identify opportunities for expansion. Metrics analyzed
included number of medication orders verified per hour, number of pharmacy dosing
consultations, and number of patient discharge counseling sessions. A pilot study
was conducted to assess the feasibility of this service and potential resident
learning opportunities. A learning experience description was drafted, and
feedback was solicited regarding the development of educational components
utilized throughout the rotation. Pharmacists who were providing services to
similar patient populations were identified to serve as preceptors. Staff
pharmacists were deployed to previously uncovered patient care units, with
pharmacy residents providing decentralized services on previously covered areas.
A rotating preceptor schedule was developed based on geographic proximity and
clinical expertise. An initial postimplementation assessment of this resident
driven service revealed that pharmacy residents provided a comparable level of
pharmacy services to that of staff pharmacists. Feedback collected from nurses,
physicians, and pharmacy staff also supported residents' ability to operate
sufficiently in this role to optimize patient care. CONCLUSION: A learning
experience developed for pharmacy residents in a large medical center enabled the
expansion of decentralized clinical services without requiring additional
pharmacist full-time equivalents.
PMID- 28687554
TI - Innovative models for providing clinical pharmacy services to remote locations
using clinical video telehealth.
AB - PURPOSE: The use of videoconferencing and other telehealth technologies to expand
access to clinical pharmacy services at multiple Veterans Affairs (VA) clinics in
rural areas of Alaska and the northwestern United States is described. SUMMARY:
Beginning in 2014, clinical pharmacy specialists at a regional VA Telehealth Hub
based at Boise VA Medical Center in Idaho have provided telehealth services for
16 clinics. In one telehealth model, a pharmacist and other remotely located
primary care team members (a medical provider, a medical support assistant, a
social worker, and a psychologist) conduct telehealth visits with veterans
located at VA clinics, with support provided by clinic-based nursing staff; this
model has been used to improve medication management services for veterans in
sparsely populated areas. In the second VA telehealth model, a remotely located
pharmacist uses telehealth technology to participate in clinical encounters along
with primary care team members located at the patient site; this model allows on
demand remote coverage in the event of planned or unplanned absences of clinic
based pharmacists. Since the Telehealth Hub was established, pharmacists have
engaged in video encounters and provided other telehealth-based clinical services
to more than 1,200 veterans with diabetes, hyperlipidemia, hypertension, and
other chronic conditions. CONCLUSION: Within the VA healthcare system, telehealth
technology has been demonstrated to be a cost-effective and well-received means
of providing clinical pharmacy services in rural areas.
PMID- 28687555
TI - Visual compatibility of colistin injection with other antibiotics during
simulated Y-site administration.
AB - PURPOSE: The compatibility of colistin with other antibiotics at concentrations
commonly used in intensive care units was studied. METHODS: A vial of colistin
was dissolved in sterile water for injection. The reconstituted solution
(colistin base 75 mg/mL) was then diluted in 0.9% sodium chloride injection in
polyvinyl chloride (PVC) infusion bag to give a total volume of 100 mL (colistin
1.5 mg/mL). Secondary drugs, including cefoperazone-sulbactam, ceftazidime,
ertapenem, fosfomycin, imipenem-cilastatin, linezolid, meropenem, piperacillin
tazobactam, and vancomycin, were reconstituted if necessary and then diluted in
0.9% sodium chloride injection in PVC infusion bags to give final study
concentrations of one-hundredth of their initial concentrations. The admixtures
were collected in beakers at the end of the i.v. line and stored at 26 degrees C
under constant fluorescent light throughout the study. Compatibility was assessed
visually during delivery of each drug pair at time 0 and at 1 hour after starting
the infusion. Compatibility was defined as the absence of visually detected
particulate formation, haze, precipitation, color change, or gas evolution. Each
combination was tested in triplicate. RESULTS: No particulate formation or other
evidence of incompatibility was found in any of the studied drug combinations
when observed immediately after mixing or at 1 hour. No particulate matter was
observed with the unaided eyes, during microscopic evaluation, or against black
and white backgrounds. CONCLUSION: Colistin 1.5 mg/mL was visually compatible
with single concentrations of 9 other antimicrobial products during simulated Y
site injection at 26 degrees C without light protection for at least 1 hour.
PMID- 28687556
TI - Spatiotemporal Proteomic Profiling of Human Cerebral Development.
AB - Mass spectrometry (MS) analysis of human post-mortem central nervous system (CNS)
tissue and induced pluripotent stem cell (iPSC)-based directed differentiations
offer complementary avenues to define protein signatures of neurodevelopment.
Methodological improvements of formalin-fixed, paraffin-embedded (FFPE) protein
isolation now enable widespread proteomic analysis of well-annotated archival
tissue samples in the context of development and disease. Here, we utilize a
shotgun label-free quantification (LFQ) MS method to profile magnetically
enriched human cortical neurons and neural progenitor cells (NPCs) derived from
iPSCs. We use these signatures to help define spatiotemporal protein dynamics of
developing human FFPE cerebral regions. We show that the use of high resolution Q
Exactive mass spectrometers now allow simultaneous quantification of >2700
proteins in a single LFQ experiment and provide sufficient coverage to define
novel biomarkers and signatures of NPC maintenance and differentiation.
Importantly, we show that this abbreviated strategy allows efficient recovery of
novel cytoplasmic, membrane-specific and synaptic proteins that are shared
between both in vivo and in vitro neuronal differentiation. This study highlights
the discovery potential of non-comprehensive high-throughput proteomic profiling
of unfractionated clinically well-annotated FFPE human tissue from a diverse
array of development and diseased states.
PMID- 28687558
TI - Seizure management in children requiring palliative care: a review of current
practice.
AB - OBJECTIVES: Controlling seizures in children approaching death can be difficult,
and there is a limited evidence base to guide best practice. We compared current
practice against the guidance for seizure management produced by the Association
of Paediatric Palliative Medicine (APPM). METHODS: Retrospective case note review
of episodes of challenging seizure management in children receiving end-of-life
care over a 10-year period (2006-2015) in the south-west region of England.
RESULTS: We reviewed 19 admissions, in 18 individuals. Six (33%) had a
malignancy, nine (50%) had a progressive neurodegenerative condition and three
(17%) had a static neurological condition with associated epilepsy. Thirteen
(72%) died in their local hospice, four (22%) at home, and one (6%) in hospital.
Seventeen of 19 episodes involved the use of subcutaneous or intravenous
midazolam infusion, for a mean of 11 days (range 3-27). There was a wide range of
starting doses of midazolam, and 9/17 (53%) received final doses in excess of
current dose recommendations. Six individuals received subcutaneous phenobarbital
infusions, with four of these (67%) receiving final doses in excess of current
dose recommendations. Plans for adjustments of infusion rates, maximal doses or
alternative approaches should treatment fail were inconsistent or absent. In
16/18 (88%) cases seizures were successfully controlled prior to the day of the
child's death. Staff found the experience of managing seizures at end of life
challenging and stressful. CONCLUSIONS: Pharmacological approaches to seizure
management in end-of-life care are variable, often exceeding APPM dose
recommendations. Despite this, safe and effective seizure control was possible in
all settings.
PMID- 28687559
TI - Integrating chaplaincy into healthcare: a survey shows providers are interested
in technology-based options.
PMID- 28687560
TI - Unsustainable pressure on GPs has led to dip in patient satisfaction, says BMA.
PMID- 28687557
TI - A PIF1/PIF3-HY5-BBX23 Transcription Factor Cascade Affects Photomorphogenesis.
AB - Light signaling plays an essential role in controlling higher plants' early
developmental process termed as photomorphogenesis. Transcriptional regulation is
a vital mechanism that is orchestrated by transcription factors and other
regulatory proteins working in concert to finely tune gene expression. Although
many transcription factors/regulators have been characterized in the light
signaling pathway, their interregulation remains largely unknown. Here, we show
that PHYTOCHROME-INTERACTING FACTOR3 (PIF3) and PIF1 transcription factors
directly bind to the regulatory regions of ELONGATED HYPOCOTYL5 (HY5) and a B-box
gene BBX23 and activate their expression in Arabidopsis (Arabidopsis thaliana).
We found that BBX23 and its close homolog gene BBX22 play a redundant role in
regulating hypocotyl growth, and that plants overexpressing BBX23 display reduced
hypocotyl elongation under red, far-red, and blue light conditions. Intriguingly,
BBX23 transcription is inhibited by light, whereas its protein is degraded in
darkness. Furthermore, we demonstrate that HY5 physically interacts with BBX23,
and these two proteins coordinately regulate the expression of both light-induced
and light-repressed genes. BBX23 is also recruited to the promoter sequences of
the light-responsive genes in a partial HY5-dependent manner. Taken together, our
study reveals that the transcriptional cascade consisting of PIF1/PIF3, HY5, and
BBX23 controls photomorphogenesis, providing a transcriptional regulatory layer
by which plants fine-tune their growth in response to changing light environment.
PMID- 28687562
TI - Efficacy and safety of the subcutaneous implantable cardioverter defibrillator: a
systematic review.
AB - BACKGROUND: Subcutaneous implantable cardioverter defibrillators (S-ICDs) are
considered an alternative to conventional transvenous ICDs (TV-ICDs) in patients
not requiring pacing. METHODS: We searched MEDLINE and EMBASE for studies
evaluating efficacy and safety outcomes in S-ICD patients. Outcomes were pooled
across studies. RESULTS: Sixteen studies were included with 5380 participants
(mean age range 33-56 years). Short-term follow-up data were available for 1670
subjects. The most common complication was pocket infection, affecting 2.7%.
Other complications included delayed wound healing (0.6%) and wound discomfort
(0.8%). 3.8% of S-ICDs were explanted, most commonly for pocket infection.
Mortality rates in hospital (0.4%) and during follow-up (3.4% from 12 studies
reporting) were low. Incidence of ventricular arrhythmia varied from 0% to 12%.
Overall shock efficacy exceeded 96%. Inappropriate shocks affected 4.3% and was
most commonly caused by T-wave oversensing. CONCLUSIONS: Although long-term
randomised data are lacking, observational data suggest similar shock efficacy
and short-term complication rates between the S-ICD and TV-ICD.
PMID- 28687561
TI - Impact of Vascular Hemodynamics on Aortic Stenosis Evaluation: New Insights Into
the Pathophysiology of Normal Flow-Small Aortic Valve Area-Low Gradient Pattern.
AB - BACKGROUND: About 50% of normal-flow/low-gradient patients (ie, low mean gradient
[MG] or peak aortic jet velocity and small aortic valve area) have severe aortic
valve calcification as measured by computed tomography. However, they are
considered to have moderate aortic stenosis (AS) in current American College of
Cardiology/American Heart Association guidelines. The objective was thus to
evaluate the effect of hypertension and reduced arterial compliance (rAC) on MG
and Vpeak measurements. METHODS AND RESULTS: Doppler-echocardiography was
performed in 4 sheep with experimentally induced severe and critical AS at: (1)
normal aortic pressure, (2) during hypertension, and (3) with rAC. Hypertension
and rAC induced a substantial decrease in MG/Vpeak compared with normal stage
(both P<=0.03) despite a stable transvalvular flow (P>0.16). Hypertension and rAC
resulted in a greater reduction of MG in critical (-42%) compared with severe (
35%) AS (P?0.0001). Comprehensive Doppler-echocardiography and computed
tomography were performed in 220 AS patients (mean age: 69+/-13 years; MG 29+/-18
mm Hg) with normal flow. The population was divided in 3 groups according to the
presence of hypertension and rAC. The slope of the linear association between
MG/Vpeak and aortic valve calcification divided by the cross-sectional area of
the aortic annulus was significantly reduced in patients with hypertension and/or
rAC compared with normotensive/normal AC patients (P<0.01). Accordingly, patients
with normal-flow/low-gradient and severe aortic valve calcification density were
more frequent in hypertension and rAC groups compared with the
normotensive/normal-AC group (16% and 12% compared with 2%; P=0.03). CONCLUSIONS:
Hypertension and rAC are associated with a substantial reduction in MG/Vpeak for
similar aortic valve calcification (ie, similar AS anatomic severity), which may
lead to underestimation of AS hemodynamic severity.
PMID- 28687564
TI - New SNPs from Testicular Cancer GWAS.
AB - Two new genome-wide association studies identify 30 new risk variants for
testicular cancer. One study suggests that genes involved in transcription
regulation during development and microtubule assembly promote development of the
disease. The second study implicates genes involved in mitochondrial metabolism,
germ cell maturation, and DNA damage repair.
PMID- 28687563
TI - Axitinib treatment in advanced RAI-resistant differentiated thyroid cancer (DTC)
and refractory medullary thyroid cancer (MTC).
AB - BACKGROUND: Axitinib, an antiangiogenic multikinase inhibitor (MKI), was
evaluated in the compassionate use programme (CUP) in Spain (October 2012
November 2014). SUBJECTS AND METHODS: 47 patients with advanced radioactive
iodine (RAI)-refractory differentiated thyroid cancer (DTC, n = 34) or medullary
thyroid cancer (MTC, n = 13) with documented disease progression were treated
with axitinib 5 mg b.i.d. The primary efficacy endpoint was objective response
rate (ORR) by Response Evaluation Criteria In Solid Tumors (RECIST) v1.1.
Progression-free survival (PFS) and adverse events (AEs) were secondary
objectives. Regulatory authorities validated the CUP, and all patients signed
informed consent form. RESULTS: Axitinib was administered as first-line therapy
in 17 patients (36.2%), as second-line in 18 patients (38.3%) and as third/fourth
line in 12 patients (25.5%). With a median follow-up of 11.5 months (0-24.3), ORR
was 27.7% (DTC: 29.4% and MTC: 23.1%) and median PFS was 8.1 months (95% CI: 4.1
12.2) (DTC: 7.4 months (95% CI: 3.1-11.8) and MTC: 9.4 months (95% CI: 4.8
13.9)). Better outcomes were reported with first-line axitinib, with an ORR of
53% and a median PFS of 13.6 months compared with 16.7% and 10.6 months as second
line treatment. Twelve (25.5%) patients required dose reduction to 3 mg b.i.d.
All-grade AEs included asthenia (53.2%), diarrhoea (36.2%), hypertension (31.9%)
and mucositis (29.8%); grade 3/4 AEs included anorexia (6.4%), diarrhoea (4.3%)
and cardiac toxicity (4.3%). CONCLUSION: Axitinib had a tolerable safety profile
and clinically meaningful activity in refractory and progressive thyroid cancer
regardless of histology as first-line therapy. To our knowledge, this is the
first time that cross-resistance between MKIs is suggested in thyroid cancer,
highlighting the importance of prospective sequential clinical studies.
PMID- 28687567
TI - Correction: Nods for Atezolizumab and Nivolumab from FDA.
PMID- 28687571
TI - Reducing the Cost of Cancer Care: When Less Is More.
PMID- 28687570
TI - Race and Ethnicity: A Part of the Equation for Personalized Clinical Decision
Making?
PMID- 28687572
TI - Point: The Imprecise Pursuit of Precision Medicine: Are Biomarkers to Blame?
PMID- 28687573
TI - Counterpoint: Successes in the Pursuit of Precision Medicine: Biomarkers Take
Credit.
PMID- 28687574
TI - Successful Treatment of Recurrent Primitive Myxoid Mesenchymal Tumor of Infancy
With BCOR Internal Tandem Duplication.
AB - Primitive myxoid mesenchymal tumor of infancy (PMMTI) is a rare tumor with <20
cases reported to date. Recently PMMTI tumors have been found to harbor BCOR
internal tandem duplication (ITD), the same genetic alteration detected in clear
cell sarcoma of the kidney (CCSK). Complete surgical resection of PMMTI is often
curative, but no standard of care has been established for unresectable tumors.
We describe a female patient who presented at 13 months of age with a paraspinal
mass and spinal cord compression. Histology was consistent with PMMTI, and the
tumor was found to harbor BCOR ITD. The patient experienced disease recurrences
after multiple surgical resections. After failing to respond to vincristine and
actinomycin therapy, the patient demonstrated a nearly complete response to a
doxorubicin-containing chemotherapy regimen. The patient's therapy was
consolidated with proton beam radiotherapy, and she has remained in remission for
>12 months after the conclusion of therapy. This case confirms BCOR ITD as a key
finding in PMMTI. The therapeutic approach described here is similar to that used
for CCSK and provides a model for the treatment of PMMTI not amenable to complete
surgical resection.
PMID- 28687575
TI - Value Tools for Patients in Cancer Care.
AB - In order to empower patients as partners in their healthcare decisions, there is
an identified need for value tools that provide enough information to help them
make decisions regarding their cancer care journey. NCCN convened a
multistakeholder working group to identify the gaps and needs of current value
tools and develop a set of findings and recommendations for the evolution of
value tools for patients. The findings and recommendations of the working group
were then presented at the Value Tools for Patients in Cancer Care Patient
Advocacy Summit in December 2016, and multistakeholder roundtable panel
discussions explored these findings and recommendations along with additional
items. This article encapsulates the discussion from the NCCN Working Group
meetings and the NCCN Patient Advocacy Summit, including identified gaps and
needs in defining value in cancer care, identified principles and parameters of
value tools for patients in cancer care, and consensus statements and
recommendations offered by the NCCN Working Group.
PMID- 28687577
TI - Frailty Index Developed From a Cancer-Specific Geriatric Assessment and the
Association With Mortality Among Older Adults With Cancer.
AB - Background: An objective measure is needed to identify frail older adults with
cancer who are at increased risk for poor health outcomes. The primary objective
of this study was to develop a frailty index from a cancer-specific geriatric
assessment (GA) and evaluate its ability to predict all-cause mortality among
older adults with cancer. Patients and Methods: Using a unique and novel data set
that brings together GA data with cancer-specific and long-term mortality data,
we developed the Carolina Frailty Index (CFI) from a cancer-specific GA based on
the principles of deficit accumulation. CFI scores (range, 0-1) were categorized
as robust (0-0.2), pre-frail (0.2-0.35), and frail (>0.35). The primary outcome
for evaluating predictive validity was all-cause mortality. The Kaplan-Meier
method and log-rank tests were used to compare survival between frailty groups,
and Cox proportional hazards regression models were used to evaluate
associations. Results: In our sample of 546 older adults with cancer, the median
age was 72 years, 72% were women, 85% were white, and 47% had a breast cancer
diagnosis. Overall, 58% of patients were robust, 24% were pre-frail, and 18% were
frail. The estimated 5-year survival rate was 72% in robust patients, 58% in pre
frail patients, and 34% in frail patients (log-rank test, P<.0001). Frail
patients had more than a 2-fold increased risk of all-cause mortality compared
with robust patients (adjusted hazard ratio, 2.36; 95% CI, 1.51-3.68).
Conclusions: The CFI was predictive of all-cause mortality in older adults with
cancer, a finding that was independent of age, sex, cancer type and stage, and
number of medical comorbidities. The CFI has the potential to become a tool that
oncologists can use to objectively identify frailty in older adults with cancer.
PMID- 28687578
TI - A Practice-Based Evaluation of Distress Screening Protocol Adherence and Medical
Service Utilization.
AB - Background: This study examined the extent to which cancer programs demonstrated
adherence to their own prescribed screening protocol, and whether adherence to
that protocol was associated with medical service utilization. The hypothesis is
that higher rates of service utilization are associated with lower rates of
adherence to screening protocols. Methods: Oncology social workers at Commission
on Cancer-accredited cancer programs reviewed electronic health records (EHRs) in
their respective cancer programs during a 2-month period in 2014. Rates of
overall adherence to a prescribed distress screening protocol were calculated
based on documentation in the EHR that screening adherence and an appropriate
clinical response had occurred. We examined documentation of emergency department
(ED) use and hospitalization within 2 months after the screening visit. Results:
Review of 8,409 EHRs across 55 cancer centers indicated that the overall
adherence rate to screening protocols was 62.7%. The highest rates of adherence
were observed in Community Cancer Programs (76.3%) and the lowest rates were in
NCI-designated Cancer Centers (43.3%). Rates of medical service utilization were
significantly higher than expected when overall protocol adherence was lacking.
After controlling for patient and institutional characteristics, risk ratios for
ED use (0.82) and hospitalization (0.81) suggest that when overall protocol
adherence was documented, 18% to 19% fewer patients used these medical services.
Conclusions: The observed associations between a mandated psychosocial care
protocol and medical service utilization suggest opportunities for operational
efficiencies and costs savings. Further investigations of protocol integrity, as
well as the clinical care models by which psychosocial care is delivered, are
warranted.
PMID- 28687576
TI - NCCN Guidelines Insights: Antiemesis, Version 2.2017.
AB - The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for
Antiemesis address all aspects of management for chemotherapy-induced nausea and
vomiting. These NCCN Guidelines Insights focus on recent updates to the NCCN
Guidelines for Antiemesis, specifically those regarding carboplatin, granisetron,
and olanzapine.
PMID- 28687579
TI - Validation of the 8th Edition of the UICC/AJCC Staging System for Nasopharyngeal
Carcinoma From Endemic Areas in the Intensity-Modulated Radiotherapy Era.
AB - Background: In this study, we evaluated the 8th edition of the Union for
International Cancer Control (UICC)/AJCC staging system for nasopharyngeal
carcinoma (NPC) in an endemic area, with the aim of validating its applicability
and providing further information for future refinements. Methods: A total of
1,790 patients with newly diagnosed, non-distant metastatic, histologically
proven NPC treated with intensity-modulated radiotherapy (IMRT) were
retrospectively reviewed. The performance of various staging systems was compared
using the Akaike information criterion (AIC) and Harrell's concordance index (c
index). Results: For N (node) category, the survival curves of different groups
according to the 8th edition were well-separated, and the prognostic model
predicted outcomes fairly well. The 8th edition had higher AIC and c-index values
for all end points than the 7th edition. However, probably due to the improved
locoregional control provided by IMRT, the survival curves for T2 and T3 almost
overlapped, without significant differences in locoregional failure-free survival
(P=.606) and disease-free survival (P=.735). Due to the difficultly of
differentiating T2 and T3, the AIC and c-index values were similar for the T
categories of the 7th and 8th editions. Similarly, the overall survival and
disease-free survival curves for stage II and III disease were not clearly
separated for either the 8th or 7th editions. Conclusions: The 8th edition of the
UICC/AJCC staging system for NPC enables more accurate prediction of treatment
outcomes. However, several limitations need to be addressed in future editions,
and it would be reasonable to further optimize the T category classification.
PMID- 28687580
TI - Accuracy of Referring Provider and Endoscopist Impressions of Colonoscopy
Indication.
AB - Background: Referring provider and endoscopist impressions of colonoscopy
indication are used for clinical care, reimbursement, and quality reporting
decisions; however, the accuracy of these impressions is unknown. This study
assessed the sensitivity, specificity, positive and negative predictive value,
and overall accuracy of methods to classify colonoscopy indication, including
referring provider impression, endoscopist impression, and administrative
algorithm compared with gold standard chart review. Methods: We randomly sampled
400 patients undergoing a colonoscopy at a Veterans Affairs health system between
January 2010 and December 2010. Referring provider and endoscopist impressions of
colonoscopy indication were compared with gold-standard chart review. Indications
were classified into 4 mutually exclusive categories: diagnostic, surveillance,
high-risk screening, or average-risk screening. Results: Of 400 colonoscopies,
26% were performed for average-risk screening, 7% for high-risk screening, 26%
for surveillance, and 41% for diagnostic indications. Accuracy of referring
provider and endoscopist impressions of colonoscopy indication were 87% and 84%,
respectively, which were significantly higher than that of the administrative
algorithm (45%; P<.001 for both). There was substantial agreement between
endoscopist and referring provider impressions (kappa=0.76). All 3 methods showed
high sensitivity (>90%) for determining screening (vs nonscreening) indication,
but specificity of the administrative algorithm was lower (40.3%) compared with
referring provider (93.7%) and endoscopist (84.0%) impressions. Accuracy of
endoscopist, but not referring provider, impression was lower in patients with a
family history of colon cancer than in those without (65% vs 84%; P=.001).
Conclusions: Referring provider and endoscopist impressions of colonoscopy
indication are both accurate and may be useful data to incorporate into
algorithms classifying colonoscopy indication.
PMID- 28687581
TI - Acute Myeloid Leukemia, Version 3.2017, NCCN Clinical Practice Guidelines in
Oncology.
AB - Acute myeloid leukemia (AML) is the most common form of acute leukemia among
adults and accounts for the largest number of annual deaths due to leukemias in
the United States. This portion of the NCCN Guidelines for AML focuses on
management and provides recommendations on the workup, diagnostic evaluation, and
treatment options for younger (age <60 years) and older (age >=60 years) adult
patients.
PMID- 28687583
TI - Abdominal Pain With Boring-Like Character: The Revolution Is Yet to Come.
PMID- 28687582
TI - Role of Alternative Donor Allogeneic Transplants in the Therapy of Acute Myeloid
Leukemia.
AB - Adult acute myeloid leukemia (AML) is often associated with a poor prognosis,
with allogeneic transplantation representing the greatest chance of cure for
eligible patients. Historically, the preferred donor source is a human leukocyte
antigen-matched blood relative, although only approximately 30% of patients have
access to such a donor. Alternative donor sources, including matched unrelated
donors, umbilical cord blood, and haploidentical related donors, are available
for almost every patient and are increasingly being used for patients without a
matched related donor. Survival outcomes with these alternative donor sources now
approximate those of matched related donor transplants. Given the safety and
success of alternative donor transplants, comparative trials are needed to
reassess the optimal donor source for patients with AML. This review summarizes
the available data on these alternative donor transplants. Further investigation
is needed to contemporize donor selection algorithms, but, in the current era,
donor availability should no longer preclude a patient's eligibility for an
allogeneic blood or marrow transplant.
PMID- 28687585
TI - NCCN News.
PMID- 28687586
TI - A rash with a heavy heart.
AB - Cardiac amyloidosis (CA) is relatively rare and frequently misdiagnosed. Other
disorders presenting with increased left ventricular (LV) mass can mimic its
diagnosis. This case illustrates unique findings of primary light chain (AL)
amyloidosis in a patient with remarkable signs of CA. Here, we report a 49-year
old man with prior diagnosis of hypertrophy cardiomyopathy (HCM) based on an
echocardiogram performed 1 year earlier that presented with 8 weeks of
periorbital rash. He had numbness in the past 3 years. More recently, he
presented with shortness of breath. Physical examination was remarkable for
periorbital purpura, macroglossia, and orthostatic hypotension. Cardiac
auscultation showed S3 and S4. Electrocardiography (ECG) showed diffuse low
voltage QRS complexes. Echocardiography revealed severe diastolic impairment;
granular "sparkling" pattern of the myocardium with thickened walls, interatrial
septum, and valves; and pericardial effusion. Diastolic dysfunction and thick
walls with low ECG voltage are compelling diagnostic findings. Laboratory work up
showed increased free light chain-differential (FLC-diff), N-terminal fragment of
brain natriuretic peptide (NT-BNP), and cardiac Troponin T (cTnT). Bone marrow
biopsy confirmed AL amyloidosis. A diagnosis of AL amyloidosis with cardiac
involvement mimicking HCM was made. The patient died during hospitalization due
to sudden cardiac death. This cases illustrates the importance of the combination
of clinical, serological, electro- and echocardiographic findings to establish
the diagnosis of CA.
PMID- 28687587
TI - FoxO1 regulates myocardial glucose oxidation rates via transcriptional control of
pyruvate dehydrogenase kinase 4 expression.
AB - Pyruvate dehydrogenase (PDH) is the rate-limiting enzyme for glucose oxidation
and a critical regulator of metabolic flexibility during the fasting to feeding
transition. PDH is regulated via both PDH kinases (PDHK) and PDH phosphatases,
which phosphorylate/inactivate and dephosphorylate/activate PDH, respectively.
Our goal was to determine whether the transcription factor forkhead box O1
(FoxO1) regulates PDH activity and glucose oxidation in the heart via increasing
the expression of Pdk4, the gene encoding PDHK4. To address this question, we
differentiated H9c2 myoblasts into cardiac myocytes and modulated FoxO1 activity,
after which Pdk4/PDHK4 expression and PDH phosphorylation/activity were assessed.
We assessed binding of FoxO1 to the Pdk4 promoter in cardiac myocytes in
conjunction with measuring the role of FoxO1 on glucose oxidation in the isolated
working heart. Both pharmacological (1 uM AS1842856) and genetic (siRNA mediated)
inhibition of FoxO1 decreased Pdk4/PDHK4 expression and subsequent PDH
phosphorylation in H9c2 cardiac myocytes, whereas 10 uM dexamethasone-induced
Pdk4/PDHK4 expression was abolished via pretreatment with 1 uM AS1842856.
Furthermore, transfection of H9c2 cardiac myocytes with a vector expressing FoxO1
increased luciferase activity driven by a Pdk4 promoter construct containing the
FoxO1 DNA-binding element region, but not in a Pdk4 promoter construct lacking
this region. Finally, AS1842856 treatment in fasted mice enhanced glucose
oxidation rates during aerobic isolated working heart perfusions. Taken together,
FoxO1 directly regulates Pdk4 transcription in the heart, thereby controlling PDH
activity and subsequent glucose oxidation rates.NEW & NOTEWORTHY Although studies
have shown an association between FoxO1 activity and pyruvate dehydrogenase
kinase 4 expression, our study demonstrated that pyruvate dehydrogenase kinase 4
is a direct transcriptional target of FoxO1 (but not FoxO3/FoxO4) in the heart.
Furthermore, we report here, for the first time, that FoxO1 inhibition increases
glucose oxidation in the isolated working mouse heart.
PMID- 28687589
TI - The Seahorses.
PMID- 28687588
TI - The carotid baroreflex modifies the pressor threshold of the muscle metaboreflex
in humans.
AB - The purpose of the present study was to test our hypothesis that unloading the
carotid baroreceptors alters the threshold and gain of the muscle metaboreflex in
humans. Ten healthy subjects performed a static handgrip exercise at 50% of
maximum voluntary contraction. Contraction was sustained for 15, 30, 45, and 60 s
and was followed by 3 min of forearm circulatory arrest, during which forearm
muscular pH is known to decrease linearly with increasing contraction time. The
carotid baroreceptors were unloaded by applying 0.1-Hz sinusoidal neck pressure
(oscillating from +15 to +50 mmHg) during ischemia. We estimated the threshold
and gain of the muscle metaboreflex by analyzing the relationship between the
cardiovascular responses during ischemia and the amount of work done during the
exercise. In the condition with unloading of the carotid baroreceptors, the
muscle metaboreflex thresholds for mean arterial blood pressure (MAP) and total
vascular resistance (TVR) corresponded to significantly lower work levels than
the control condition (threshold for MAP: 795 +/- 102 vs. 662 +/- 208 mmHg and
threshold for TVR: 818 +/- 213 vs. 572 +/- 292 kg.s, P < 0.05), but the gains did
not differ between the two conditions (gain for MAP: 4.9 +/- 1.7 vs. 4.4 +/- 1.6
mmHg.kg.s-1.100 and gain for TVR: 1.3 +/- 0.8 vs. 1.3 +/- 0.7 mmHg.l-1.min-1.kg.s
1.100). We conclude that the carotid baroreflex modifies the muscle metaboreflex
threshold in humans. Our results suggest the carotid baroreflex brakes the muscle
metaboreflex, thereby inhibiting muscle metaboreflex-mediated pressor and
vasoconstriction responses.NEW & NOTEWORTHY We found that unloading the carotid
baroreceptors shifts the pressor threshold of the muscle metaboreflex toward
lower metabolic stimulation levels in humans. This finding indicates that, in the
normal loading state, the carotid baroreflex inhibits the muscle metaboreflex
pressor response by shifting the reflex threshold to higher metabolic stimulation
levels.
PMID- 28687590
TI - On Amyloid Protein.
PMID- 28687591
TI - Atrophy.
PMID- 28687593
TI - Effect of controlled ovarian hyperstimulation on puberty and estrus in mice
offspring.
AB - Controlled ovarian hyperstimulation (COH) is widely used for the treatment of
infertility, while the long-term effects of COH on the reproductive function in
female offspring are currently unknown. Based on the fact that COH could cause
high E2 levels in women throughout pregnancy and excess estrogenic exposure
during fetal development is harmful to subsequent adult ovarian function, we
assumed the hypothesis that COH disrupts reproductive function in female
offspring. To test this hypothesis, COH was induced in mice to obtain female
offspring by pregnant mare serum gonadotropin (PMSG) and HCG, and then we
evaluated pubertal transition, serum levels of E2, anti-Mullerian hormone (AMH),
FSH and LH, mRNA expressions of Esr1, Amhr2, Fshr and Lhcgr in ovaries, number of
follicles and ovarian histology. We also investigated the apoptosis of follicles
by TUNEL; the mRNA expressions of Fas, FasL, Bax, Bcl2, and caspase 3, 8 and 9 by
quantitative real-time PCR; and the protein expressions of cleaved-caspase (CASP)
3, 8 and 9 by Western blot. Moreover, we further observed estrous cyclicity in
young adult offspring, performed follicle counting and measured the level of AMH
in both serum and ovary. COH could induce detrimental pregnancy outcomes, as well
as delayed pubertal transition and irregular estrous cycle due to the aberrant
growth and maturation of follicles in female offspring. Our novel findings add
new evidence to better understand the potential risks of COH on the reproductive
function in female offspring, raising the awareness that COH could exert adverse
effects on female offspring, rather than just obtain more oocytes for
fertilization.
PMID- 28687595
TI - UK lags far behind Europe on diagnosis of dementia with Lewy bodies.
PMID- 28687594
TI - Reduced threshold for store overload-induced Ca2+ release is a common defect of
RyR1 mutations associated with malignant hyperthermia and central core disease.
AB - Mutations in the skeletal muscle ryanodine receptor (RyR1) cause malignant
hyperthermia (MH) and central core disease (CCD), whereas mutations in the
cardiac ryanodine receptor (RyR2) lead to catecholaminergic polymorphic
ventricular tachycardia (CPVT). Most disease-associated RyR1 and RyR2 mutations
are located in the N-terminal, central, and C-terminal regions of the
corresponding ryanodine receptor (RyR) isoform. An increasing body of evidence
demonstrates that CPVT-associated RyR2 mutations enhance the propensity for
spontaneous Ca2+ release during store Ca2+ overload, a process known as store
overload-induced Ca2+ release (SOICR). Considering the similar locations of
disease-associated RyR1 and RyR2 mutations in the RyR structure, we hypothesize
that like CPVT-associated RyR2 mutations, MH/CCD-associated RyR1 mutations also
enhance SOICR. To test this hypothesis, we determined the impact on SOICR of 12
MH/CCD-associated RyR1 mutations E2347-del, R2163H, G2434R, R2435L, R2435H, and
R2454H located in the central region, and Y4796C, T4826I, L4838V, A4940T, G4943V,
and P4973L located in the C-terminal region of the channel. We found that all
these RyR1 mutations reduced the threshold for SOICR. Dantrolene, an acute
treatment for MH, suppressed SOICR in HEK293 cells expressing the RyR1 mutants
R164C, Y523S, R2136H, R2435H, and Y4796C. Interestingly, carvedilol, a commonly
used beta-blocker that suppresses RyR2-mediated SOICR, also inhibits SOICR in
these RyR1 mutant HEK293 cells. Therefore, these results indicate that a reduced
SOICR threshold is a common defect of MH/CCD-associated RyR1 mutations, and that
carvedilol, like dantrolene, can suppress RyR1-mediated SOICR. Clinical studies
of the effectiveness of carvedilol as a long-term treatment for MH/CCD or other
RyR1-associated disorders may be warranted.
PMID- 28687596
TI - Expression and light-dependent translocation of beta-arrestin in the visual
system of the terrestrial slug Limax valentianus.
AB - Vertebrates, cephalopods and arthropods are equipped with eyes that have the
highest spatiotemporal resolution among the animal phyla. In parallel, only
animals in these three phyla have visual arrestin specialized for the termination
of visual signaling triggered by opsin, in addition to ubiquitously expressed
beta-arrestin that serves in terminating general G protein-coupled receptor
signaling. Indeed, visual arrestin in Drosophila and rodents translocates to the
opsin-rich subcellular region in response to light to reduce the overall
sensitivity of photoreceptors in an illuminated environment (i.e. light
adaptation). We thus hypothesized that, during evolution, visual arrestin has
taken over the role of beta-arrestin in those animals with eyes of high
spatiotemporal resolution. If this is true, it is expected that beta-arrestin
plays a role similar to visual arrestin in those animals with low-resolution
eyes. In the present study, we focused on the terrestrial mollusk Limax
valentianus, a species related to cephalopods but that has only beta-arrestin,
and generated antibodies against beta-arrestin. We found that beta-arrestin is
highly expressed in photosensory neurons, and translocates into the microvilli of
the rhabdomere within 30 min in response to short wavelength light (400 nm), to
which the Limax eye exhibits a robust response. These observations suggest that
beta-arrestin functions in the visual system of those animals that do not have
visual arrestin. We also exploited anti-beta-arrestin antibody to visualize the
optic nerve projecting to the brain, and demonstrated its usefulness for tracing
a visual ascending pathway.
PMID- 28687597
TI - Accumulation of mitochondrial DNA mutations disrupts cardiac progenitor cell
function and reduces survival.
PMID- 28687598
TI - Whoa man! Unexpected protein O-mannosylation pathways in mammals.
AB - The recent expansion of well-characterized O-mannosylated mammalian proteins
beyond the archetypical example of alpha-dystroglycan has inspired new interest
in the possibility of additional functional roles of this modification. In an
effort to explore those roles, a new study now serendipitously uncovers the
existence of an alternative pathway to the well-described POMT (protein O
mannosyltransferase) family of O-mannosyltransferases.
PMID- 28687599
TI - PSMA Ligands for PET Imaging of Prostate Cancer.
AB - Targeting the prostate-specific membrane antigen (PSMA) with 68Ga-labeled and 18F
labeled PET agents has become increasingly important in recent years. Imaging of
biochemically recurrent prostate cancer has been established as a widely accepted
clinical indication for PSMA ligand PET/CT in many parts of the world because of
the results of multiple, primarily retrospective, studies that indicate superior
detection efficacy compared with standard-of-care imaging. For high-risk primary
prostate cancer, evidence is growing that this modality significantly aids in the
detection of otherwise occult nodal and bone metastases. For both clinical
indications in recurrent as well as in primary prostate cancer, preliminary data
demonstrate a substantial impact on clinical management. Emerging data imply that
intraprostatic tumor localization, therapy stratification, and treatment
monitoring of advanced disease in specific clinical situations might become
future indications. Current criteria for image reporting of PSMA ligand PET are
evolving given the expanding body of literature on physiologic and pathologic
uptake patterns and pitfalls. This article intends to give an educational
overview on the current status of PSMA ligand PET imaging, including imaging
procedure and interpretation, clinical indications, diagnostic potential, and
impact on treatment planning.
PMID- 28687601
TI - Operational and Dosimetric Aspects of Pediatric PET/CT.
AB - No consistent guidelines exist for the acquisition of a CT scan as part of
pediatric PET/CT. Given that children may be more vulnerable to the effects of
ionizing radiation, it is necessary to develop methods that provide diagnostic
quality imaging when needed, in the shortest time and with the lowest patient
radiation exposure. This article describes the basics of CT dosimetry and PET/CT
acquisition in children. We describe the variability in pediatric PET/CT
techniques, based on a survey of 19 PET/CT pediatric institutions in North
America. The results of the survey demonstrated that, although most institutions
used automatic tube current modulation, there remained a large variation of
practice, on the order of a factor of 2-3, across sites, pointing to the need for
guidelines. We introduce the approach developed at our institution for using a
multiseries PET/CT acquisition technique that combines diagnostic-quality CT in
the essential portion of the field of view and a low-dose technique to image the
remainder of the body. This approach leads to a reduction in radiation dose to
the patient while combining the PET and the diagnostic CT into a single
acquisition. The standardization of pediatric PET/CT provides an opportunity for
a reduction in the radiation dose to these patients while maintaining an
appropriate level of diagnostic image quality.
PMID- 28687600
TI - Pretargeted Imaging and Therapy.
AB - In vivo pretargeting stands as a promising approach to harnessing the exquisite
tumor-targeting properties of antibodies for nuclear imaging and therapy while
simultaneously skirting their pharmacokinetic limitations. The core premise of
pretargeting lies in administering the targeting vector and radioisotope
separately and having the 2 components combine within the body. In this manner,
pretargeting strategies decrease the circulation time of the radioactivity,
reduce the uptake of the radionuclide in healthy nontarget tissues, and
facilitate the use of short-lived radionuclides that would otherwise be
incompatible with antibody-based vectors. In this short review, we seek to
provide a brief yet informative survey of the 4 preeminent mechanistic approaches
to pretargeting, strategies predicated on streptavidin and biotin, bispecific
antibodies, complementary oligonucleotides, and bioorthogonal click chemistry.
PMID- 28687602
TI - Imaging B Cells in a Mouse Model of Multiple Sclerosis Using 64Cu-Rituximab PET.
AB - B lymphocytes are a key pathologic feature of multiple sclerosis (MS) and are
becoming an important therapeutic target for this condition. Currently, there is
no approved technique to noninvasively visualize B cells in the central nervous
system (CNS) to monitor MS disease progression and response to therapies. Here,
we evaluated 64Cu-rituximab, a radiolabeled antibody specifically targeting the
human B cell marker CD20, for its ability to image B cells in a mouse model of MS
using PET. Methods: To model CNS infiltration by B cells, experimental autoimmune
encephalomyelitis (EAE) was induced in transgenic mice that express human CD20 on
B cells. EAE mice were given subcutaneous injections of myelin oligodendrocyte
glycoprotein fragment1-125 emulsified in complete Freund adjuvant. Control mice
received complete Freund adjuvant alone. PET imaging of EAE and control mice was
performed 1, 4, and 19 h after 64Cu-rituximab administration. Mice were perfused
and sacrificed after the final PET scan, and radioactivity in dissected tissues
was measured with a gamma-counter. CNS tissues from these mice were immunostained
to quantify B cells or were further analyzed via digital autoradiography.
Results: Lumbar spinal cord PET signal was significantly higher in EAE mice than
in controls at all evaluated time points (e.g., 1 h after injection: 5.44 +/-
0.37 vs. 3.33 +/- 0.20 percentage injected dose [%ID]/g, P < 0.05). 64Cu
rituximab PET signal in brain regions ranged between 1.74 +/- 0.11 and 2.93 +/-
0.15 %ID/g for EAE mice, compared with 1.25 +/- 0.08 and 2.24 +/- 0.11 %ID/g for
controls (P < 0.05 for all regions except striatum and thalamus at 1 h after
injection). Similarly, ex vivo biodistribution results revealed notably higher
64Cu-rituximab uptake in the brain and spinal cord of huCD20tg EAE, and B220
immunostaining verified that increased 64Cu-rituximab uptake in CNS tissues
corresponded with elevated B cells. Conclusion: B cells can be detected in the
CNS of EAE mice using 64Cu-rituximab PET. Results from these studies warrant
further investigation of 64Cu-rituximab in EAE models and consideration of use in
MS patients to evaluate its potential for detecting and monitoring B cells in the
progression and treatment of this disease. These results represent an initial
step toward generating a platform to evaluate B cell-targeted therapeutics en
route to the clinic.
PMID- 28687603
TI - Interaction between Scene and Object Processing Revealed by Human fMRI and MEG
Decoding.
AB - Scenes strongly facilitate object recognition, such as when we make out the shape
of a distant boat on the water. Yet, although known to interact in perception,
neuroimaging research has primarily provided evidence for separate scene- and
object-selective cortical pathways. This raises the question of how these
pathways interact to support context-based perception. Here we used a novel
approach in human fMRI and MEG studies to reveal supra-additive scene-object
interactions. Participants (men and women) viewed degraded objects that were hard
to recognize when presented in isolation but easy to recognize within their
original scene context, in which no other associated objects were present. fMRI
decoding showed that the multivariate representation of the objects' category
(animate/inanimate) in object-selective cortex was strongly enhanced by the
presence of scene context, even though the scenes alone did not evoke category
selective response patterns. This effect in object-selective cortex was
correlated with concurrent activity in scene-selective regions. MEG decoding
results revealed that scene-based facilitation of object processing peaked at 320
ms after stimulus onset, 100 ms later than peak decoding of intact objects.
Together, results suggest that expectations derived from scene information,
processed in scene-selective cortex, feed back to shape object representations in
visual cortex. These findings characterize, in space and time, functional
interactions between scene- and object-processing pathways.SIGNIFICANCE STATEMENT
Although scenes and objects are known to contextually interact in visual
perception, the study of high-level vision has mostly focused on the dissociation
between their selective neural pathways. The current findings are the first to
reveal direct facilitation of object recognition and neural representation by
scene background, even in the absence of contextually associated objects. Using a
multivariate approach to both fMRI and MEG, we characterize the functional
neuroanatomy and neural dynamics of such scene-based object facilitation.
Finally, the correlation of this effect with scene-selective activity suggests
that, although functionally distinct, scene and object processing pathways do
interact at a perceptual level to fill in for insufficient visual detail.
PMID- 28687604
TI - Calpain Inhibition Is Protective in Machado-Joseph Disease Zebrafish Due to
Induction of Autophagy.
AB - The neurodegenerative disease Machado-Joseph disease (MJD), also known as
spinocerebellar ataxin-3, affects neurons of the brain and spinal cord,
disrupting control of the movement of muscles. We have successfully established
the first transgenic zebrafish (Danio rerio) model of MJD by expressing human
ataxin-3 protein containing either 23 glutamines (23Q, wild-type) or 84Q (MJD
causing) within neurons. Phenotypic characterization of the zebrafish (male and
female) revealed that the ataxin-3-84Q zebrafish have decreased survival compared
with ataxin-3-23Q and develop ataxin-3 neuropathology, ataxin-3 cleavage
fragments and motor impairment. Ataxin-3-84Q zebrafish swim shorter distances
than ataxin-3-23Q zebrafish as early as 6 days old, even if expression of the
human ataxin-3 protein is limited to motor neurons. This swimming phenotype
provides a valuable readout for drug treatment studies. Treating the EGFP-ataxin
3-84Q zebrafish with the calpain inhibitor compound calpeptin decreased levels of
ataxin-3 cleavage fragments, but also removed all human ataxin-3 protein
(confirmed by ELISA) and prevented the early MJD zebrafish motor phenotype. We
identified that this clearance of ataxin-3 protein by calpeptin treatment
resulted from an increase in autophagic flux (indicated by decreased p62 levels
and increased LC3II). Cotreatment with the autophagy inhibitor chloroquine
blocked the decrease in human ataxin-3 levels and the improved movement produced
by calpeptin treatment. This study demonstrates that this first transgenic
zebrafish model of MJD is a valuable tool for testing potential treatments for
MJD. Calpeptin treatment is protective in this model of MJD and removal of human
ataxin-3 through macro-autophagy plays an important role in this beneficial
effect.SIGNIFICANCE STATEMENT We have established the first transgenic zebrafish
model of the neurodegenerative disease MJD, and identified relevant disease
phenotypes, including impaired movement from an early age, which can be used in
rapid drug testing studies. We have found that treating the MJD zebrafish with
the calpain inhibitor compound calpeptin produces complete removal of human
ataxin-3 protein, due to induction of the autophagy quality control pathway. This
improves the movement of the MJD zebrafish. Artificially blocking the autophagy
pathway prevents the removal of human ataxin-3 and improved movement produced by
calpeptin treatment. These findings indicate that induction of autophagy, and
removal of ataxin-3 protein, plays an important role in the protective effects of
calpain inhibition for the treatment of MJD.
PMID- 28687605
TI - Alterations in Functional Cortical Hierarchy in Hemiparkinsonian Rats.
AB - Parkinson's disease and experimentally induced hemiparkinsonism are characterized
by increased beta synchronization between cortical and subcortical areas. This
change in beta connectivity might reflect either a symmetric increase in
interareal influences or asymmetric changes in directed influences among brain
areas. We assessed patterns of functional and directed connectivity within and
between striatum and six cortical sites in each hemisphere of the
hemiparkinsonian rat model. LFPs were recorded in resting and walking states,
before and after unilateral 6-hydroxydopamine lesion. The hemiparkinsonian state
was characterized by increased oscillatory activity in the 20-40 Hz range in
resting and walking states, and increased interhemispheric coupling (phase lag
index) that was more widespread at rest than during walking. Spectral Granger
causality analysis revealed that the change in symmetric functional connectivity
comprised profound reorganization of hierarchical organization and directed
influence patterns. First, in the lesioned hemisphere, the more anterior,
nonprimary motor areas located at the top of the cortical hierarchy (i.e.,
receiving many directed influences) tended to increase their directed influence
onto the posterior primary motor and somatosensory areas. This enhanced influence
of "higher" areas may be related to the loss of motor control due to the 6-OHDA
lesion. Second, the drive from the nonlesioned toward the lesioned hemisphere (in
particular to striatum) increased, most prominently during walking. The nature of
these adaptations (disturbed signaling or compensation) is discussed. The present
study demonstrates that hemiparkinsonism is associated with a profound
reorganization of the hierarchical organization of directed influence patterns
among brain areas, perhaps reflecting compensatory processes.SIGNIFICANCE
STATEMENT Parkinson's disease classically first becomes manifest in one hemibody
before affecting both sides, suggesting that degeneration is asymmetrical. Our
results suggest that asymmetrical degeneration of the dopaminergic system induces
an increased drive from the nonlesioned toward the lesioned hemisphere and a
profound reorganization of functional cortical hierarchical organization, leading
to a stronger directed influence of hierarchically higher placed cortical areas
over primary motor and somatosensory cortices. These changes may represent a
compensatory mechanism for loss of motor control as a consequence of dopamine
depletion.
PMID- 28687606
TI - cAMP-dependent regulation of IKs single-channel kinetics.
AB - The delayed potassium rectifier current, IKs , is composed of KCNQ1 and KCNE1
subunits and plays an important role in cardiac action potential repolarization.
During beta-adrenergic stimulation, 3'-5'-cyclic adenosine monophosphate (cAMP)
dependent protein kinase A (PKA) phosphorylates KCNQ1, producing an increase in
IKs current and a shortening of the action potential. Here, using cell-attached
macropatches and single-channel recordings, we investigate the microscopic
mechanisms underlying the cAMP-dependent increase in IKs current. A membrane
permeable cAMP analog, 8-(4-chlorophenylthio)-cAMP (8-CPT-cAMP), causes a marked
leftward shift of the conductance-voltage relation in macropatches, with or
without an increase in current size. Single channels exhibit fewer silent sweeps,
reduced first latency to opening (control, 1.61 +/- 0.13 s; cAMP, 1.06 +/- 0.11
s), and increased higher-subconductance-level occupancy in the presence of cAMP.
The E160R/R237E and S209F KCNQ1 mutants, which show fixed and enhanced voltage
sensor activation, respectively, largely abolish the effect of cAMP. The
phosphomimetic KCNQ1 mutations, S27D and S27D/S92D, are much less and not at all
responsive, respectively, to the effects of PKA phosphorylation (first latency of
S27D + KCNE1 channels: control, 1.81 +/- 0.1 s; 8-CPT-cAMP, 1.44 +/- 0.1 s, P <
0.05; latency of S27D/S92D + KCNE1: control, 1.62 +/- 0.1 s; cAMP, 1.43 +/- 0.1
s, nonsignificant). Using total internal reflection fluorescence microscopy, we
find no overall increase in surface expression of the channel during exposure to
8-CPT-cAMP. Our data suggest that the cAMP-dependent increase in IKs current is
caused by an increase in the likelihood of channel opening, combined with faster
openings and greater occupancy of higher subconductance levels, and is mediated
by enhanced voltage sensor activation.
PMID- 28687607
TI - Synaptotagmin isoforms confer distinct activation kinetics and dynamics to
chromaffin cell granules.
AB - Adrenomedullary chromaffin cells respond to sympathetic nervous system activation
by secreting a cocktail of potent neuropeptides and hormones into the
circulation. The distinct phases of the chromaffin cell secretory response have
been attributed to the progressive fusion of distinct populations of dense core
granules with different activation kinetics. However, it has been difficult to
define what distinguishes these populations at the molecular level. Functional
segregation of granule pools may depend on selective sorting of synaptotagmin-1
(Syt-1) and synaptotagmin-7 (Syt-7), which our previous work showed are rarely
cosorted to the same granule. Here we assess the consequences of selective
sorting of Syt isoforms in chromaffin cells, particularly with respect to granule
dynamics and activation kinetics. Upon depolarization of cells expressing
fluorescent Syt isoforms using elevated K+, we find that Syt-7 granules fuse with
faster kinetics than Syt-1 granules, irrespective of stimulation strength.
Pharmacological blockade of Ca2+ channels reveals differential dependence of Syt
1 versus Syt-7 granule exocytosis on Ca2+ channel subtypes. Syt-7 granules also
show a greater tendency to fuse in clusters than Syt-1 granules, and granules
harboring Syt-1 travel a greater distance before fusion than those with Syt-7,
suggesting that there is spatial and fusion-site heterogeneity among the two
granule populations. However, the greatest functional difference between granule
populations is their responsiveness to Ca2+ Upon introduction of Ca2+ into
permeabilized cells, Syt-7 granules fuse with fast kinetics and high efficacy,
even at low Ca2+ levels (e.g., when cells are weakly stimulated). Conversely, Syt
1 granules require a comparatively larger increase in intracellular Ca2+ for
activation. At Ca2+ concentrations above 30 uM, activation kinetics are faster
for Syt-1 granules than for Syt-7 granules. Our study provides evidence for
functional specialization of chromaffin cell granules via selective expression of
Syt isoforms with different Ca2+ sensitivities.
PMID- 28687608
TI - Thioredoxin reductase from Toxoplasma gondii: an essential virulence effector
with antioxidant function.
AB - Thioredoxin reductase (TR) can help pathogens resist oxidative-burst injury from
host immune cells by maintaining a thioredoxin-reduction state during NADPH
consumption. TR is a necessary virulence factor that enables the persistent
infection of some parasites. We performed bioinformatics analyses and biochemical
assays to characterize the activity, subcellular localization, and genetic
ablation of Toxoplasma gondii TR (TgTR), to shed light on its biologic function.
We expressed the TgTR protein with an Escherichia coli expression system and
analyzed its enzyme activity, reporting a Km for the recombinant TgTR of 11.47
15.57 MUM, using NADPH as a substrate, and 130.48-151.09 MUM with dithio-bis
nitrobenzoic acid as a substrate. The TgTR sequence shared homology with that of
TR, but lacked a selenocysteine residue in the C-terminal region and was thought
to contain 2 flavin adenine dinucleotide (FAD) domains and 1 NADPH domain. In
addition, immunoelectron microscopy results showed that TgTR was widely dispersed
in the cytoplasm, and we observed that parasite antioxidant capacity, invasion
efficiency, and proliferation were decreased in TR-knockout (TR-KO) strains in
vitro, although this strain still stimulated the release of reactive oxygen
species release in mouse macrophages while being more sensitive to H2O2 toxicity
in vitro Furthermore, our in vivo results revealed that the survival time of mice
infected with the TR-KO strain was significantly prolonged relative to that of
mice infected with the wild-type strain. These results suggest that TgTR plays an
important role in resistance to oxidative damage and can be considered a
virulence factor associated with T. gondii infection.-Xue, J., Jiang, W., Chen,
Y., Gong, F., Wang, M., Zeng, P., Xia, C., Wang, Q., Huang, K. Thioredoxin
reductase from Toxoplasma gondii: an essential virulence effector with
antioxidant function.
PMID- 28687609
TI - Deguelin exerts potent nematocidal activity via the mitochondrial respiratory
chain.
AB - As a result of limited classes of anthelmintics and an over-reliance on chemical
control, there is a great need to discover new compounds to combat drug
resistance in parasitic nematodes. Here, we show that deguelin, a plant-derived
rotenoid, selectively and potently inhibits the motility and development of
nematodes, which supports its potential as a lead candidate for drug development.
Furthermore, we demonstrate that deguelin treatment significantly increases gene
transcription that is associated with energy metabolism, particularly oxidative
phosphorylation and mitoribosomal protein production before inhibiting motility.
Mitochondrial tracking confirmed enhanced oxidative phosphorylation. In
accordance, real-time measurements of oxidative phosphorylation in response to
deguelin treatment demonstrated an immediate decrease in oxygen consumption in
both parasitic (Haemonchus contortus) and free-living (Caenorhabditis elegans)
nematodes. Consequently, we hypothesize that deguelin is exerting its toxic
effect on nematodes as a modulator of oxidative phosphorylation. This study
highlights the dynamic biologic response of multicellular organisms to deguelin
perturbation.-Preston, S., Korhonen, P. K., Mouchiroud, L., Cornaglia, M., McGee,
S. L., Young, N. D., Davis, R. A., Crawford, S., Nowell, C., Ansell, B. R. E.,
Fisher, G. M., Andrews, K. T., Chang, B. C. H., Gijs, M. A. M., Sternberg, P. W.,
Auwerx, J., Baell, J., Hofmann, A., Jabbar, A., Gasser, R. B. Deguelin exerts
potent nematocidal activity via the mitochondrial respiratory chain.
PMID- 28687610
TI - Regulator of G-protein signaling Gbeta5-R7 is a crucial activator of muscarinic
M3 receptor-stimulated insulin secretion.
AB - In pancreatic beta cells, muscarinic cholinergic receptor M3 (M3R) stimulates
glucose-induced secretion of insulin. Regulator of G-protein signaling (RGS)
proteins are critical modulators of GPCR activity, yet their role in beta cells
remains largely unknown. R7 subfamily RGS proteins are stabilized by the G
protein subunit Gbeta5, such that the knockout of the Gnb5 gene results in
degradation of all R7 subunits. We found that Gnb5 knockout in mice or in the
insulin-secreting MIN6 cell line almost completely eliminates insulinotropic
activity of M3R. Moreover, overexpression of Gbeta5-RGS7 strongly promotes M3R
stimulated insulin secretion. Examination of this noncanonical mechanism in Gnb5
/- MIN6 cells showed that cAMP, diacylglycerol, or Ca2+ levels were not
significantly affected. There was no reduction in the amplitude of free Ca2+
responses in islets from the Gnb5-/- mice, but the frequency of Ca2+ oscillations
induced by cholinergic agonist was lowered by more than 30%. Ablation of Gnb5
impaired M3R-stimulated phosphorylation of ERK1/2. Stimulation of the ERK pathway
in Gnb5-/- cells by epidermal growth factor restored M3R-stimulated insulin
release to near normal levels. Identification of the novel role of Gbeta5-R7 in
insulin secretion may lead to a new therapeutic approach for improving pancreatic
beta-cell function.-Wang, Q., Pronin, A. N., Levay, K., Almaca, J., Fornoni, A.,
Caicedo, A., Slepak, V. Z. Regulator of G-protein signaling Gbeta5-R7 is a
crucial activator of muscarinic M3 receptor-stimulated insulin secretion.
PMID- 28687611
TI - Vitamin A regulates Akt signaling through the phospholipid fatty acid
composition.
AB - Protein kinases, including the serine/threonine kinase Akt, mediate manifold
bioactivities of vitamin A, although the mechanisms behind the sustained kinase
activation are diffuse. To investigate the role of cellular lipids as targetable
factors in Akt signaling, we combined mass spectrometry-based lipidomics with
immunologic detection of Akt (Ser473) phosphorylation. A screening campaign
revealed retinol (vitamin A alcohol) and all-trans retinoic acid (vitamin A acid)
(RA) as hits that time-dependently (>=24 h) deplete phosphatidylcholine-bound
polyunsaturated fatty acids (PUFA-PCs) from NIH-3T3 mouse fibroblasts while
inducing Akt activation (EC50 ~ 0.1-1 uM). Other mitogenic and stress-regulated
kinases were hardly affected. Organized in a coregulated phospholipid subcluster,
PUFA-PCs compensated for the RA-induced loss of cellular PUFA-PCs and diminished
Akt activation when supplemented. The counter-regulation of phospholipids and Akt
by RA was mimicked by knockdown of lysophosphatidylcholine acyltransferase-3 or
the selective retinoid X receptor (RXR) agonist bexarotene and prevented by the
selective RXR antagonist Hx531. Treatment of mice with retinol decreased the
tissue ratio of PUFA-PC and enhanced basal Akt activation preferentially in
brain, which was attributed to astrocytes in dissociated cortical cultures.
Together, our findings show that RA regulates the long-term activation of Akt by
changes in the phospholipid composition.-Pein, H., Koeberle, S. C., Voelkel, M.,
Schneider, F., Rossi, A., Thurmer, M., Loeser, K., Sautebin, L., Morrison, H.,
Werz, O., Koeberle, A. Vitamin A regulates Akt signaling through the phospholipid
fatty acid composition.
PMID- 28687613
TI - Valproic acid induces aberrant development of striatal compartments and
corticostriatal pathways in a mouse model of autism spectrum disorder.
AB - The striatum comprises two neurochemical compartments: striosomes and the matrix.
Striosomal and matrix compartments receive inputs from limbic system-related and
sensorimotor cortices, respectively. Here, we investigate the impact on the
corticostriosomal pathway in the valproic acid (VPA)-induced autism spectrum
disorder mouse model. VPA administration during the neurogenesis time windows of
striosomes, but not the matrix, resulted in aberrant compartmentation [i.e.,
maternal VPA injections at embryonic day (E)12.75 decreased MU-opioid receptor
positive striosomes, but increased calbindin-positive matrix in the rostral
striatum]. VPAE12.75 treatment also impaired the aggregation of cells pulse
labeled with 5-bromo-2'-deoxyuridine at E12.75 into striosomal cell clusters,
which suggests defective segregation of striosomal cells from matrix cells. This
possibility was supported by our findings that VPAE12.75 treatment altered the
expression of ephrinA5 and EphA4, two molecules that are related to compartmental
segregation. In the VPAE12.75 neocortex, Foxp2-positive neurons were decreased in
layer VI, but increased in layer V, which projects to the striosomal compartment.
We also investigated VPA effects on the corticostriosomal pathway. VPAE12.75
treatment decreased the putative corticostriosomal synapses of striosomal neurons
and induced an aberrant pattern of isolation stress-induced ultrasonic
vocalizations. Of interest, risperidone treatments conjointly improved ultrasonic
vocalizations and restored the striosomal compartment in VPAE12.75 pups.
Collectively, dysfunctional corticostriatal pathways, particularly via the
aberrant striosomal compartment, may be involved in autism spectrum disorder
pathophysiology.-Kuo, H.-Y., Liu, F.-C. Valproic acid induces aberrant
development of striatal compartments and corticostriatal pathways in a mouse
model of autism spectrum disorder.
PMID- 28687612
TI - Endothelial microparticles prevent lipid-induced endothelial damage via Akt/eNOS
signaling and reduced oxidative stress.
AB - Endothelial microparticles (EMPs) are endothelium-derived submicron vesicles that
are released in response to diverse stimuli and are elevated in cardiovascular
disease, which is correlated with risk factors. This study investigates the
effect of EMPs on endothelial cell function and dysfunction in a model of free
fatty acid (FFA) palmitate-induced oxidative stress. EMPs were generated from TNF
alpha-stimulated HUVECs and quantified by using flow cytometry. HUVECs were
treated with and without palmitate in the presence or absence of EMPs. EMPs were
found to carry functional eNOS and to protect against oxidative stress by
positively regulating eNOS/Akt signaling, which restored NO production, increased
superoxide dismutase and catalase, and suppressed NADPH oxidase and reactive
oxygen species (ROS) production, with the involvement of NF-erythroid 2-related
factor 2 and heme oxygenase-1. Conversely, under normal conditions, EMPs reduced
NO release and increased ROS and redox-sensitive marker expression. In addition,
functional assays using EMP-treated mouse aortic rings that were performed under
homeostatic conditions demonstrated a decline in endothelium-dependent
vasodilatation, but restored the functional response under lipid-induced
oxidative stress. These data indicate that EMPs harbor functional eNOS and
potentially play a role in the feedback loop of damage and repair during
homeostasis, but are also effective in protecting against FFA-induced oxidative
stress; thus, EMP function is reflected by the microenvironment.-Mahmoud, A. M.,
Wilkinson, F. L., McCarthy, E. M., Moreno-Martinez, D., Langford-Smith, A.,
Romero, M., Duarte, J., Alexander, M. Y. Endothelial microparticles prevent lipid
induced endothelial damage via Akt/eNOS signaling and reduced oxidative stress.
PMID- 28687614
TI - Signal integration at the PI3K-p85-XBP1 hub endows coagulation protease activated
protein C with insulin-like function.
AB - Coagulation proteases have increasingly recognized functions beyond hemostasis
and thrombosis. Disruption of activated protein C (aPC) or insulin signaling
impair function of podocytes and ultimately cause dysfunction of the glomerular
filtration barrier and diabetic kidney disease (DKD). We here show that insulin
and aPC converge on a common spliced-X-box binding protein-1 (sXBP1) signaling
pathway to maintain endoplasmic reticulum (ER) homeostasis. Analogous to insulin,
physiological levels of aPC maintain ER proteostasis in DKD. Accordingly,
genetically impaired protein C activation exacerbates maladaptive ER response,
whereas genetic or pharmacological restoration of aPC maintains ER proteostasis
in DKD models. Importantly, in mice with podocyte-specific deficiency of insulin
receptor (INSR), aPC selectively restores the activity of the cytoprotective ER
transcription factor sXBP1 by temporally targeting INSR downstream signaling
intermediates, the regulatory subunits of PI3Kinase, p85alpha and p85beta. Genome
wide mapping of condition-specific XBP1-transcriptional regulatory patterns
confirmed that concordant unfolded protein response target genes are involved in
maintenance of ER proteostasis by both insulin and aPC. Thus, aPC efficiently
employs disengaged insulin signaling components to reconfigure ER signaling and
restore proteostasis. These results identify ER reprogramming as a novel
hormonelike function of coagulation proteases and demonstrate that targeting
insulin signaling intermediates may be a feasible therapeutic approach
ameliorating defective insulin signaling.
PMID- 28687615
TI - SOX5/6/21 Prevent Oncogene-Driven Transformation of Brain Stem Cells.
AB - Molecular mechanisms preventing self-renewing brain stem cells from oncogenic
transformation are poorly defined. We show that the expression levels of SOX5,
SOX6, and SOX21 (SOX5/6/21) transcription factors increase in stem cells of the
subventricular zone (SVZ) upon oncogenic stress, whereas their expression in
human glioma decreases during malignant progression. Elevated levels of SOX5/6/21
promoted SVZ cells to exit the cell cycle, whereas genetic ablation of SOX5/6/21
dramatically increased the capacity of these cells to form glioma-like tumors in
an oncogene-driven mouse brain tumor model. Loss-of-function experiments revealed
that SOX5/6/21 prevent detrimental hyperproliferation of oncogene expressing SVZ
cells by facilitating an antiproliferative expression profile. Consistently,
restoring high levels of SOX5/6/21 in human primary glioblastoma cells enabled
expression of CDK inhibitors and decreased p53 protein turnover, which blocked
their tumorigenic capacity through cellular senescence and apoptosis. Altogether,
these results provide evidence that SOX5/6/21 play a central role in driving a
tumor suppressor response in brain stem cells upon oncogenic insult. Cancer Res;
77(18); 4985-97. (c)2017 AACR.
PMID- 28687618
TI - Huwe1 Sustains Normal Ovarian Epithelial Cell Transformation and Tumor Growth
through the Histone H1.3-H19 Cascade.
AB - Ubiquitination-directed protein degradation is important in many cancers for
tumor initiation and maintenance, and E3 ligases containing HECT domains are
emerging as new therapeutic targets. In contrast to many other E3 ligases, the
role of HUWE1 in ovarian cancer where HUWE1 is dysregulated has been unclear.
Here we report that genetic deletion of Huwe1 in the mouse inhibits
transformation of ovary surface epithelium cells without significantly affecting
cell survival and apoptosis, and that Huwe1 deletion after tumors have been
initiated inhibits tumor growth. In Huwe1-deficient cells, expression of histone
H1.3 increased, inhibiting the expression of noncoding RNA H19H19 silencing
phenocopied the effects of Huwe1 deficiency, whereas H1.3 silencing partially
rescued the expression of H19 and the Huwe1-null phenotype. Inducible silencing
of HUWE1 in human ovarian cancer cells produced a similar phenotype.
Mechanistically, HUWE1 bound and ubiquitinated H1.3, which was consequently
marked for destruction by proteasomes. Our results establish that HUWE1 plays an
essential role in promoting ovarian cancer. Cancer Res; 77(18); 4773-84. (c)2017
AACR.
PMID- 28687617
TI - Proinflammatory CXCL12-CXCR4/CXCR7 Signaling Axis Drives Myc-Induced Prostate
Cancer in Obese Mice.
AB - Obesity is a prognostic risk factor in the progression of prostate cancer;
however, the molecular mechanisms involved are unclear. In this study, we provide
preclinical proof of concept for the role of a proinflammatory CXCL12-CXCR4/CXCR7
signaling axis in an obesity-driven mouse model of myc-induced prostate cancer.
Analysis of the stromal vascular fraction from periprostatic white adipose tissue
from obese HiMyc mice at 6 months of age revealed a dramatic increase in mRNAs
encoding various chemokines, cytokines, growth factors, and angiogenesis
mediators, with CXCL12 among the most significantly upregulated genes.
Immunofluorescence staining of ventral prostate tissue from obese HiMyc mice
revealed high levels of CXCL12 in the stromal compartment as well as high
staining for CXCR4 and CXCR7 in the epithelial compartment of tumors. Prostate
cancer cell lines derived from HiMyc tumors (HMVP2 and derivative cell lines)
displayed increased protein expression of both CXCR4 and CXCR7 compared with
protein lysates from a nontumorigenic prostate epithelial cell line (NMVP cells).
CXCL12 treatment stimulated migration and invasion of HMVP2 cells but not NMVP
cells. These effects of CXCL12 on HMVP2 cells were inhibited by the CXCR4
antagonist AMD3100 as well as knockdown of either CXCR4 or CXCR7. CXCL12
treatment also produced rapid activation of STAT3, NFkappaB, and MAPK signaling
in HMVP2 cells, which was again attenuated by either AMD3100 or knockdown of
CXCR4 or CXCR7. Collectively, these data suggest that CXCL12 secreted by stromal
cells activates invasiveness of prostate cancer cells and may play a role in
driving tumor progression in obesity. Targeting the CXCL12-CXCR4/CXCR7 axis could
lead to novel approaches for offsetting the effects of obesity on prostate cancer
progression. Cancer Res; 77(18); 5158-68. (c)2017 AACR.
PMID- 28687616
TI - Posttranscriptional Regulation of PARG mRNA by HuR Facilitates DNA Repair and
Resistance to PARP Inhibitors.
AB - The majority of pancreatic ductal adenocarcinomas (PDAC) rely on the mRNA
stability factor HuR (ELAV-L1) to drive cancer growth and progression. Here, we
show that CRISPR-Cas9-mediated silencing of the HuR locus increases the relative
sensitivity of PDAC cells to PARP inhibitors (PARPi). PDAC cells treated with
PARPi stimulated translocation of HuR from the nucleus to the cytoplasm,
specifically promoting stabilization of a new target, poly (ADP-ribose)
glycohydrolase (PARG) mRNA, by binding a unique sequence embedded in its 3'
untranslated region. HuR-dependent upregulation of PARG expression facilitated
DNA repair via hydrolysis of polyADP-ribose on related repair proteins.
Accordingly, strategies to inhibit HuR directly promoted DNA damage accumulation,
inefficient PAR removal, and persistent PARP-1 residency on chromatin (PARP-1
trapping). Immunoprecipitation assays demonstrated that the PARP-1 protein binds
and posttranslationally modifies HuR in PARPi-treated PDAC cells. In a mouse
xenograft model of human PDAC, PARPi monotherapy combined with targeted silencing
of HuR significantly reduced tumor growth compared with PARPi therapy alone. Our
results highlight the HuR-PARG axis as an opportunity to enhance PARPi-based
therapies. Cancer Res; 77(18); 5011-25. (c)2017 AACR.
PMID- 28687619
TI - Resistance to the Antibody-Drug Conjugate T-DM1 Is Based in a Reduction in
Lysosomal Proteolytic Activity.
AB - Trastuzumab-emtansine (T-DM1) is an antibody-drug conjugate (ADC) that was
approved recently to treat HER2+ breast cancers. Despite its impressive clinical
efficacy in many patients, intrinsic and acquired resistance to T-DM1 has emerged
as a challenge. To identify mechanisms of T-DM1 resistance, we isolated several
resistant HER2+ clones exhibiting stable drug refractoriness in vitro and in vivo
Genomic comparisons showed substantial differences among three of the isolated
clones, indicating several potential mechanisms of resistance to T-DM1. However,
we observed no differences in HER2 levels and signaling among the resistant
models and parental HER2+ cells. Bioinformatics studies suggested that
intracellular trafficking of T-DM1 could underlie resistance to T-DM1, and
systematic analysis of the path followed by T-DM1 showed that the early steps in
the internalization of the drug were unaltered. However, in some of the resistant
clones, T-DM1 accumulated in lysosomes. In these clones, lysosomal pH was
increased and the proteolytic activity of these organelles was deranged. These
results were confirmed in T-DM1-resistant cells from patient-derived HER2+
samples. We postulate that resistance to T-DM1 occurs through multiple
mechanisms, one of which is impaired lysosomal proteolytic activity. Because
other ADC may use the same internalization-degradation pathway to deliver active
payloads, strategies aimed at restoring lysosomal functionality might overcome
resistance to ADC-based therapies and improve their effectiveness. Cancer Res;
77(17); 4639-51. (c)2017 AACR.
PMID- 28687620
TI - Kindlin-2 Regulates the Growth of Breast Cancer Tumors by Activating CSF-1
Mediated Macrophage Infiltration.
AB - Interplay between tumor cells and host cells in the tumor microenvironment
dictates the development of all cancers. In breast cancer, malignant cells
educate host macrophages to adopt a protumorigenic phenotype. In this study, we
show how the integrin-regulatory protein kindlin-2 (FERMT2) promotes metastatic
progression of breast cancer through the recruitment and subversion of host
macrophages. Kindlin-2 expression was elevated in breast cancer biopsy tissues
where its levels correlated with reduced patient survival. On the basis of these
observations, we used CRISPR/Cas9 technology to ablate Kindlin-2 expression in
human MDA-MB-231 and murine 4T1 breast cancer cells. Kindlin-2 deficiency
inhibited invasive and migratory properties in vitro without affecting
proliferation rates. However, in vivo tumor outgrowth was inhibited by >80% in a
manner associated with reduced macrophage infiltration and secretion of the
macrophage attractant and growth factor colony-stimulating factor-1 (CSF-1). The
observed loss of CSF-1 appeared to be caused by a more proximal deficiency in
TGFbeta-dependent signaling in Kindlin-2-deficient cells. Collectively, our
results illuminate a Kindlin-2/TGFbeta/CSF-1 signaling axis employed by breast
cancer cells to capture host macrophage functions that drive tumor progression.
Cancer Res; 77(18); 5129-41. (c)2017 AACR.
PMID- 28687622
TI - Polyphosphate as a donor of high-energy phosphate for the synthesis of ADP and
ATP.
AB - Here, we studied the potential role of inorganic polyphosphate (polyP) as an
energy source for ADP and ATP formation in the extracellular space. In SaOS-2
cells, we show that matrix vesicles are released into the extracellular space
after incubation with polyP. These vesicles contain both alkaline phosphatase
(ALP) and adenylate kinase (AK) activities (mediated by ALPL and AK1 enzymes).
Both enzymes translocate to the cell membrane in response to polyP. To
distinguish the process(es) of AMP and ADP formation during ALP hydrolysis from
the ATP generated via the AK reaction, inhibition studies with the AK inhibitor
A(5')P5(5')A were performed. We found that ADP formation in the extracellular
space occurs after enzymatic ATP synthesis. After exposure to polyP, a
significant increase of the ADP level was observed, which is likely to be been
catalyzed by ALP. This increase is not due to an intensified ATP release via
exocytosis. The ATP level in the extracellular space of SaOS-2 cells is strongly
increased in response to polyP, very likely mediated by the AK. We propose that
the ALP and AK enzymes are involved in the extracellular ADP and ATP synthesis.
PMID- 28687621
TI - Cancer-Associated Fibroblasts Share Characteristics and Protumorigenic Activity
with Mesenchymal Stromal Cells.
AB - Cancer-associated fibroblasts (CAF) have been suggested to originate from
mesenchymal stromal cells (MSC), but their relationship with MSCs is not clear.
Here, we have isolated from primary human neuroblastoma tumors a population of
alphaFAP- and FSP-1-expressing CAFs that share phenotypic and functional
characteristics with bone marrow-derived MSCs (BM-MSC). Analysis of human
neuroblastoma tumors also confirmed the presence of alphaFAP- and FSP-1-positive
cells in the tumor stroma, and their presence correlated with that of M2 tumor
associated macrophages. These cells (designated CAF-MSCs) enhanced in vitro
neuroblastoma cell proliferation, survival, and resistance to chemotherapy and
stimulated neuroblastoma tumor engraftment and growth in immunodeficient mice,
indicating an effect independent of the immune system. The protumorigenic
activity of MSCs in vitro and in xenografted mice was dependent on the
coactivation of JAK2/STAT3 and MEK/ERK1/2 in neuroblastoma cells. In a mouse
model of orthotopically implanted neuroblastoma cells, inhibition of JAK2/STAT3
and MEK/ERK/1/2 by ruxolitinib and trametinib potentiated tumor response to
etoposide and increased overall survival. These data point to a new type of
protumorigenic CAF in the tumor microenvironment of neuroblastoma and to STAT3
and ERK1/2 as mediators of their activity. Cancer Res; 77(18); 5142-57. (c)2017
AACR.
PMID- 28687624
TI - PATELLINS are regulators of auxin-mediated PIN1 relocation and plant development
in Arabidopsis thaliana.
AB - Coordinated cell polarization in developing tissues is a recurrent theme in
multicellular organisms. In plants, a directional distribution of the plant
hormone auxin is at the core of many developmental programs. A feedback
regulation of auxin on the polarized localization of PIN auxin transporters in
individual cells has been proposed as a self-organizing mechanism for coordinated
tissue polarization, but the molecular mechanisms linking auxin signalling to PIN
dependent auxin transport remain unknown. We used a microarray-based approach to
find regulators of the auxin-induced PIN relocation in Arabidopsis thaliana root,
and identified a subset of a family of phosphatidylinositol transfer proteins
(PITPs), the PATELLINs (PATLs). Here, we show that PATLs are expressed in
partially overlapping cell types in different tissues going through mitosis or
initiating differentiation programs. PATLs are plasma membrane-associated
proteins accumulated in Arabidopsis embryos, primary roots, lateral root
primordia and developing stomata. Higher order patl mutants display reduced PIN1
repolarization in response to auxin, shorter root apical meristem, and drastic
defects in embryo and seedling development. This suggests that PATLs play a
redundant and crucial role in polarity and patterning in Arabidopsis.
PMID- 28687623
TI - Nonmuscle myosin IIB regulates epicardial integrity and epicardium-derived
mesenchymal cell maturation.
AB - Nonmuscle myosin IIB (NMIIB; heavy chain encoded by MYH10) is essential for
cardiac myocyte cytokinesis. The role of NMIIB in other cardiac cells is not
known. Here, we show that NMIIB is required in epicardial formation and functions
to support myocardial proliferation and coronary vessel development. Ablation of
NMIIB in epicardial cells results in disruption of epicardial integrity with a
loss of E-cadherin at cell-cell junctions and a focal detachment of epicardial
cells from the myocardium. NMIIB-knockout and blebbistatin-treated epicardial
explants demonstrate impaired mesenchymal cell maturation during epicardial
epithelial-mesenchymal transition. This is manifested by an impaired invasion of
collagen gels by the epicardium-derived mesenchymal cells and the reorganization
of the cytoskeletal structure. Although there is a marked decrease in the
expression of mesenchymal genes, there is no change in Snail (also known as
Snai1) or E-cadherin expression. Studies from epicardium-specific NMIIB-knockout
mice confirm the importance of NMIIB for epicardial integrity and epicardial
functions in promoting cardiac myocyte proliferation and coronary vessel
formation during heart development. Our findings provide a novel mechanism
linking epicardial formation and epicardial function to the activity of the
cytoplasmic motor protein NMIIB.
PMID- 28687625
TI - A Phase II Trial Evaluating the Safety of Rapid Infusion of Ofatumumab in
Patients with Previously Treated Chronic Lymphocytic Leukemia.
AB - LESSONS LEARNED: Ofatumumab infusion reactions can be diminished by escalating
the dose rate in individual patients in sequential infusions. BACKGROUND:
Ofatumumab (OFA) is a fully humanized, anti-CD20 antibody approved for use in
chronic lymphocytic leukemia (CLL). The recommended administration requires long
infusion times. We evaluated an accelerated infusion regimen of 2 hours. METHODS:
The first dose of OFA (300 mg) was given on week 1 day 1 starting at 3.6 mg/hour
and doubling every 30 minutes until a rate of 240 mg/hour was reached. If
tolerated, the second dose (1,000 mg) was given on week 1 day 3 starting at 50
mg/hour and doubling every 30 minutes until a rate of 800 mg/hour was reached. If
tolerated, the third dose (2,000 mg) was given on week 2 day 1 at 800 mg/hour
over the first 30 minutes and, if tolerated, at 1,068 mg/hour over the next 90
minutes (goal infusion time: 120 minutes). Subsequent OFA infusions were
administered weekly in the same manner for 8 weeks, and then monthly for 4
months. RESULTS: Thirty-four patients were treated. Most infusion-related
reactions occurred during the first and second infusion. Eighty-seven percent
(87%) of patients finished the third infusion within 15 minutes of the planned 2
hours and only one had an infusion reaction. CONCLUSION: Using this stepped-up
dosing regimen, a rapid infusion of OFA is safe and well tolerated.
PMID- 28687626
TI - Antiemetic Corticosteroid Rotation from Dexamethasone to Methylprednisolone to
Prevent Dexamethasone-Induced Hiccup in Cancer Patients Treated with
Chemotherapy: A Randomized, Single-Blind, Crossover Phase III Trial.
AB - BACKGROUND: To assess whether the rotation of dexamethasone to methylprednisolone
decreases the intensity of dexamethasone-induced hiccup (DIH) in cancer patients
treated with chemotherapy. MATERIALS AND METHODS: Adult patients who experienced
DIH within 3 days after the administration of dexamethasone as an antiemetic were
screened. Eligible patients were randomly assigned to receive dexamethasone (n =
33) or methylprednisolone (n = 32) as an antiemetic (randomization phase). In the
next cycle of chemotherapy, the dexamethasone group received methylprednisolone
and vice versa in the methylprednisolone group (crossover phase). The primary
endpoint was the difference in hiccup intensity as measured using the numeric
rating scale (NRS) between two groups. RESULTS: No female patients were enrolled,
although the study did not exclude them. At the randomization phase, hiccup
frequency was 28/33 (84.8%) in the dexamethasone group versus 20/32 (62.5%) in
the methylprednisolone group (p = .04). Intensity of hiccup was significantly
higher in the dexamethasone group than that in the methylprednisolone group (mean
NRS, 3.5 vs. 1.4, p < .001). At the crossover phase, hiccup intensity was further
decreased after the rotation of dexamethasone to methylprednisolone in the
dexamethasone group (mean NRS, 3.5 to 0.9, p < .001), while it was increased by
rotating methylprednisolone to dexamethasone in the methylprednisolone group
(mean NRS, 1.4 to 3.3, p = .025). There were no differences in emesis intensity
between the two groups at either the randomization or crossover phases.
Clinicaltrials.gov identifier: NCT01974024. CONCLUSION: Dexamethasone-induced
hiccup is a male-predominant phenomenon that can be ameliorated by rotating
dexamethasone to methylprednisolone without compromising the antiemetic efficacy.
IMPLICATIONS FOR PRACTICE: In this randomized, multicenter, phase III trial,
hiccup intensity was significantly lower when the antiemetic corticosteroid was
rotated from dexamethasone to methylprednisolone without a change in emesis
intensity than that when dexamethasone was maintained. At the crossover phase,
hiccup intensity was increased again if dexamethasone was readministered instead
of methylprednisolone. The present study demonstrated that dexamethasone-induced
hiccup can be improved by rotating from dexamethasone to methylprednisolone
without compromising its antiemetic efficacy.
PMID- 28687628
TI - WHO reports increasing emergence of drug resistant gonorrhoea.
PMID- 28687627
TI - Phase II Trial of Sorafenib in Combination with Capecitabine in Patients with
Hepatocellular Carcinoma: INST 08-20.
AB - LESSONS LEARNED: There continues to be a lack of systemic options for advanced
hepatocellular carcinoma (HCC); sorafenib and, very recently, regorafenib are the
only approved options. There exists a potential to combine sorafenib with
chemotherapeutic agents shown to be active in HCC, such as capecitabine,
safely.Good tumor response was observed, with objective improvement in a few
patients seldom seen by single agent sorafenib; however, because of the limited
number of patients, meaningful conclusions on survival cannot be drawn.
BACKGROUND: Sorafenib is the currently approved first-line treatment for
hepatocellular carcinoma (HCC). Capecitabine has antitumor activity in
hepatobiliary cancers. The combination of the two, if tolerated, could possibly
improve antitumor response, and survival. METHODS: Patients with advanced HCC
ineligible for locoregional therapy, Eastern Cooperative Oncology Group
performance status of <=2, Child-Pugh class A or B-7 cirrhosis, hemoglobin >=8.5
g/dL, platelets >=50,000/MUL, absolute neutrophil count (ANC) >=1,500 cells/MUL,
and serum creatinine of <=2.0 mg/dL were recruited. All subjects received a
combination of sorafenib and capecitabine, on a 14-day 7-days on 7-days off
schedule. The primary end point was safety and secondary end points were overall
survival (OS) and disease control rate. RESULTS: A total of 15 out of 47 patients
met inclusion criteria. Median age was 64 years (56-79) and 77% were male. With a
median follow-up of 12 months, median OS was 12.7 months (95% confidence interval
[CI], 8.5-23.4). Disease control rate was 77% (complete response 8%, partial
response 8%, and stable disease 61%). Common adverse events were as follows: (a)
thrombocytopenia (64%); (b) anemia (14%); (c) hypophosphatemia (21%); (d)
hypomagnesemia (14%); (e) hyperbilirubinemia (21%); (f) increased aspartate
transaminase (AST) (14%); (g) hand-foot syndrome (21%); and (h) deep vein
thrombosis (21%). CONCLUSION: At tolerable doses, the combination of sorafenib
and capecitabine seems an active and safe palliative treatment for HCC in class A
and B-7 patients with cirrhosis. The small sample size does not allow comparison
with single-agent sorafenib.
PMID- 28687629
TI - Muscling in on mitochondrial sexual dimorphism; role of mitochondrial dimorphism
in skeletal muscle health and disease.
AB - Mitochondria are no longer solely regarded as the cellular powerhouse; instead,
they are now implicated in mediating a wide-range of cellular processes, in the
context of health and disease. A recent article in Clinical Science, Ventura
Clapier et al. highlights the role of sexual dimorphism in mitochondrial function
in health and disease. However, we feel the authors have overlooked arguably one
of the most mitochondria-rich organs in skeletal muscle. Many studies have
demonstrated that mitochondria have a central role in mediating the pathogenesis
of myopathologies. However, the impact of sexual dimorphism in this context is
less clear, with several studies reporting conflicting observations. For instance
in ageing studies, a rodent model reported female muscles have higher antioxidant
capacity compared with males; in contrast, human studies demonstrate no sex
difference in mitochondrial bioenergetics and oxidative damage. These divergent
observations highlight the importance of considering models and methods used to
examine mitochondrial function, when interpreting these data. The use of either
isolated or intact mitochondrial preparations in many studies appears likely to
be a source of discord, when comparing many studies. Overall, it is now clear
that more research is needed to determine if sexual dimorphism is a contributing
factor in the development of myopathologies.
PMID- 28687630
TI - The mitochondrial unfolded protein response: Signaling from the powerhouse.
AB - Mitochondria are multifaceted and indispensable organelles required for cell
performance. Accordingly, dysfunction to mitochondria can result in cellular
decline and possibly the onset of disease. Cells use a variety of means to
recover mitochondria and restore homeostasis, including the activation of
retrograde pathways such as the mitochondrial unfolded protein response (UPRmt).
In this Minireview, we will discuss how cells adapt to mitochondrial stress
through UPRmt regulation. Furthermore, we will explore the current repertoire of
biological functions that are associated with this essential stress-response
pathway.
PMID- 28687631
TI - Clock1a affects mesoderm development and primitive hematopoiesis by regulating
Nodal-Smad3 signaling in the zebrafish embryo.
AB - Circadian clock and Smad2/3/4-mediated Nodal signaling regulate multiple
physiological and pathological processes. However, it remains unknown whether
Clock directly cross-talks with Nodal signaling and how this would regulate
embryonic development. Here we show that Clock1a coordinated mesoderm development
and primitive hematopoiesis in zebrafish embryos by directly up-regulating Nodal
Smad3 signaling. We found that Clock1a is expressed both maternally and
zygotically throughout early zebrafish development. We also noted that Clock1a
alterations produce embryonic defects with shortened body length, lack of the
ventral tail fin, or partial defect of the eyes. Clock1a regulates the expression
of the mesodermal markers ntl, gsc, and eve1 and of the hematopoietic markers
scl, lmo2, and fli1a Biochemical analyses revealed that Clock1a stimulates Nodal
signaling by increasing expression of Smad2/3/4. Mechanistically, Clock1a
activates the smad3a promoter via its E-box1 element (CAGATG). Taken together,
these findings provide mechanistic insight into the role of Clock1a in the
regulation of mesoderm development and primitive hematopoiesis via modulation of
Nodal-Smad3 signaling and indicate that Smad3a is directly controlled by the
circadian clock in zebrafish.
PMID- 28687634
TI - Laboratory-Developed Tests: A Legislative and Regulatory Review.
AB - BACKGROUND: Twenty-five years ago, the Food and Drug Administration (FDA)
asserted in a draft document that "home brew" tests-now commonly referred to as
laboratory-developed tests (LDTs)-are subject to the same regulatory oversight as
other in vitro diagnostics (IVDs)4. In 2010, the FDA began work on developing a
proposed framework for future LDT oversight. Released in 2014, the draft guidance
sparked an intense debate over potential LDT regulation. While the proposed
guidance has not been implemented, many questions regarding LDT oversight remain
unresolved. CONTENT: This review provides an overview of federal statutes and
regulations related to IVDs and clinical laboratory operations, with a focus on
those potentially applicable to LDTs and proposed regulatory efforts. Sources
reviewed include the Code of Federal Regulations, the Federal Register,
congressional hearings, guidance and policy documents, position statements,
published literature, and websites. SUMMARY: Federal statutes regarding IVDs were
passed without substantive evidence of congressional consideration toward the
concept of LDTs. The FDA has clear oversight authority over IVD reagents
introduced into interstate commerce. A 16-year delay in publicly asserting FDA
authority over LDTs, the pursuit of a draft guidance approach toward oversight,
and establishment of regulations under the Clinical Laboratory Improvement
Amendments of 1988 (CLIA'88) applicable to LDTs contributed to community
uncertainty toward LDT oversight. Future regulatory and/or legislative efforts
may be required to resolve this uncertainty.
PMID- 28687635
TI - Tracing the Seeds in the Soil.
PMID- 28687633
TI - United States and European Multicenter Prospective Study for the Analytical
Performance and Clinical Validation of a Novel Sensitive Fully Automated
Immunoassay for Calcitonin.
AB - BACKGROUND: The objective of this study is the validation and proof of clinical
relevance of a novel electrochemiluminescence immunoassay (ECLIA) for the
determination of serum calcitonin (CT) in patients with medullary thyroid
carcinoma (MTC) and in different diseases of the thyroid and of calcium
homeostasis. METHODS: This was a multicenter prospective study on basal serum CT
concentrations performed in 9 US and European referral institutions. In addition,
stimulated CT concentrations were measured in 50 healthy volunteers after
intravenous calcium administration (2.5 mg/kg bodyweight). RESULTS: In total,
1929 patients and healthy controls were included. Limits of blank, detection, and
quantification for the ECLIA were 0.3, 0.5, and 1 ng/L, respectively. Highest
intra- and interassay coefficients of variation were 7.4% (CT concentration, 0.8
ng/L) and 7.0% (1.1 ng/L), respectively. Medians (interval) of serum CT
concentrations in 783 healthy controls were 0.8 ng/L (<0.5-12.7) and 3 ng/L (<0.5
18) for females and males, respectively (97.5th percentile, 6.8 and 11.6 ng/L,
respectively). Diagnostic sensitivity and specificity were 100%/97.1% and
96.2%/96.4%, for female/males, respectively. Patients (male/female) with primary
hyperparathyroidism, renal failure, and neuroendocrine tumors showed CT
concentrations >97.5th percentile in 33%/4.7%, 18.5%/10%, and 8.3%/12%,
females/males, respectively. Peak serum CT concentrations were reached 2 min
after calcium administration (161.7 and 111.8 ng/L in males and females,
respectively; P < 0.001). CONCLUSIONS: Excellent analytical performance, low
interindividual variability, and low impact of confounders for increased CT
concentrations in non-MTC patients indicate that the investigated assay has
appropriate clinical utility. Calcium-stimulated CT results suggest good test
applicability owing to low interindividual variability.
PMID- 28687636
TI - Acute Graft-Versus-Host Disease Prognosis: Are Biomarkers Ready for Preemptive
Clinical Trials?
PMID- 28687632
TI - Increased levels of Gab1 and Gab2 adaptor proteins skew interleukin-4 (IL-4)
signaling toward M2 macrophage-driven pulmonary fibrosis in mice.
AB - M2-polarized macrophages, also known as alternatively activated macrophages, have
long been associated with pulmonary fibrosis; however, the mechanism has not been
fully defined. Gab1 and Gab2 proteins belong to the Gab family of adaptors and
are integral components of the signal specificity in response to various
extracellular stimuli. In this report, we found that levels of both Gab1 and Gab2
were elevated in M2-polarized macrophages isolated from bleomycin-induced
fibrotic lungs. In vitro Gab1/2 deficiency in bone marrow-derived macrophages
abrogated IL-4-mediated M2 polarization. Furthermore, in vivo conditional removal
of Gab1 (Gab1MyKO) and germ line knock-out of Gab2 (Gab2-/-) in macrophages
prevented a bias toward the M2 phenotype and attenuated bleomycin-induced
fibrotic lung remodeling. In support of these observations, Gab1/2 were involved
in responses predominated by IL-4 signaling, an essential determinant for
macrophage M2 polarization. Further investigation revealed that both Gab1 and -2
are recruited to the IL-4 receptor, synergistically enhancing downstream signal
amplification but conferring IL-4 signal preference. Mechanistically, the loss of
Gab1 attenuated AKT activation, whereas the absence of Gab2 suppressed STAT6
activation in response to IL-4 stimulation, both of which are commonly attributed
to M2-driven pulmonary fibrosis in mice. Taken together, these observations
define a non-redundant role of Gab docking proteins in M2 polarization, adding
critical insights into the pathogenesis of idiopathic pulmonary fibrosis.
PMID- 28687638
TI - Behavioral Risk Assessment From Newborn to Preschool: The Value of Older
Siblings.
AB - OBJECTIVES: The aim of this study was to examine the plausibility of a risk
prediction tool in infancy for school-entry emotional and behavioral problems.
Familial aggregation has been operationalized previously as maternal
psychopathology. The hypothesis was tested that older sibling (OS)
psychopathology, as an indicator of familial aggregation, would enable a fair
level of risk prediction compared with previous research, when combined with
traditional risk factors. METHODS: By using a longitudinal design, data on child
and family risk factors were collected on 323 infants (M = 2.00 months), all of
whom had OSs. Infants were followed up 4.5 years later when both parents provided
ratings of emotional and behavioral problems. Multiple regression and receiver
operating characteristic curve analyses were conducted for emotional, conduct,
and attention problems separately. RESULTS: The emotional and behavioral problems
of OSs at infancy were the strongest predictors of the same problems in target
children 4.5 years later. Other risk factors, including maternal depression and
socioeconomic status provided extra, but weak, significant prediction. The area
under the receiver operating characteristic curve for emotional and conduct
problems yielded a fair prediction. CONCLUSIONS: This study is the first to offer
a fair degree of prediction from risk factors at birth to school-entry emotional
and behavioral problems. This degree of prediction was achieved with the
inclusion of the emotional and behavioral problems of OSs (thus limiting
generalizability to children with OSs). The inclusion of OS psychopathology
raises risk prediction to a fair level.
PMID- 28687639
TI - Preterm and low weight births rise again in the US.
PMID- 28687637
TI - Inpatient-Derived Vital Sign Parameters Implementation: An Initiative to Decrease
Alarm Burden.
AB - OBJECTIVES: To implement data-driven vital sign parameters to reduce bedside
monitor alarm burden. METHODS: Single-center, quality-improvement initiative with
historical controls assessing the impact of age-based, inpatient-derived heart
rate (HR) and respiratory rate (RR) parameters on a 20-bed acute care ward that
serves primarily pediatric cardiology patients. The primary outcome was the
number of alarms per monitored bed day (MBD) with the aim to decrease the alarms
per MBD. Balancing measures included the frequency of missed rapid response team
activations, acute respiratory code events, and cardiorespiratory arrest events
in the unit with the new vital sign parameters. RESULTS: The median number of all
cardiorespiratory monitor alarms per MBD decreased by 21% from 52 (baseline
period) to 41 (postintervention period) (P < .001). This included a 17% decrease
in the median HR alarms (9-7.5 per MBD) and a 53% drop in RR alarms (16.8-8.0 per
MBD). There were 57 rapid response team activations, 8 acute respiratory code
events, and no cardiorespiratory arrest events after the implementation of the
new parameters. An evaluation of HRs and RRs recorded at the time of the event
revealed that all patients with HRs and/or RRs out of range per former default
parameters would also be out of range with the new parameters. CONCLUSIONS:
Implementation of data-driven HR and iteratively derived RR parameters safely
decreased the total alarm frequency by 21% in a pediatric acute care unit.
PMID- 28687640
TI - Early Imaging Prediction of Malignant Cerebellar Edema Development in Acute
Ischemic Stroke.
AB - BACKGROUND AND PURPOSE: Malignant cerebellar edema (MCE) is a life-threatening
complication of acute ischemic stroke that requires timely diagnosis and
management. Aim of this study was to identify imaging predictors in initial
multiparametric computed tomography (CT), including whole-brain CT perfusion (WB
CTP). METHODS: We consecutively selected all subjects with cerebellar ischemic WB
CTP deficits and follow-up-confirmed cerebellar infarction from an initial cohort
of 2635 patients who had undergone multiparametric CT because of suspected
stroke. Follow-up imaging was assessed for the presence of MCE, measured using an
established 10-point scale, of which scores >=4 are considered malignant.
Posterior circulation-Acute Stroke Prognosis Early CT Score (pc-ASPECTS) was
determined to assess ischemic changes on noncontrast CT, CT angiography (CTA),
and parametric WB-CTP maps (cerebellar blood flow [CBF]; cerebellar blood volume;
mean transit time; time to drain). Fisher's exact tests, Mann-Whitney U tests,
and receiver operating characteristics analyses were performed for statistical
analyses. RESULTS: Out of a total of 51 patients who matched the inclusion
criteria, 42 patients (82.4%) were categorized as MCE- and 9 (17.6%) as MCE+.
MCE+ patients had larger CBF, cerebellar blood volume, mean transit time, and
time to drain deficit volumes (all with P<0.001) and showed significantly lower
median pc-ASPECTS assessed using WB-CTP (CBF, cerebellar blood volume, mean
transit time, time to drain; all with P<0.001) compared with MCE- patients, while
median pc-ASPECTS on noncontrast CT and CTA was not significantly different (both
P>0.05). Receiver operating characteristics analyses yielded the largest area
under the curve values for the prediction of MCE development for CBF (0.979) and
cerebellar blood volume deficit volumes (0.956) and pc-ASPECTS on CBF (0.935),
whereas pc-ASPECTS on noncontrast CT (0.648) and CTA (0.684) had less diagnostic
value. The optimal cutoff value for CBF deficit volume was 22 mL, yielding 100%
sensitivity and 90% specificity for MCE classification. CONCLUSIONS: WB-CTP
provides added diagnostic value for the early identification of patients at risk
for MCE development in acute cerebellar stroke.
PMID- 28687641
TI - Immediate Vascular Imaging Needed for Efficient Triage of Patients With Acute
Ischemic Stroke Initially Admitted to Nonthrombectomy Centers.
AB - BACKGROUND AND PURPOSE: Current guidelines for endovascular thrombectomy (EVT)
used to select patients for transfer to thrombectomy-capable stroke centers (TSC)
may result in unnecessary transfers. We sought to determine the impact of
simulated baseline vascular imaging on reducing unnecessary transfers and
clinical-imaging factors associated with receiving EVT after transfer. METHODS:
We identified patients with stroke transferred for EVT from 30 referring
hospitals between 2010 and 2016 who had a referring hospitals brain computed
tomography and repeat imaging on TSC arrival available for review. Initial
Alberta Stroke Program Early CT scores and TSC vascular occlusion level were
assessed. The main outcome variable was receiving EVT at TSC. Models were
simulated to derive optimal triaging parameters for EVT. RESULTS: A total of 508
patients were included in the analysis (mean age, 69+/-14 years; 42% women).
Application at referring hospitals of current guidelines for EVT yielded
sensitivity of 92% (95% confidence interval, 0.84-0.96) and specificity of 53%
(95% confidence interval, 0.48-0.57) for receiving EVT at TSC. Repeated
simulations identified optimal selection criteria for transfer as National
Institute of Health Stroke Scale >8 plus baseline vascular imaging
(sensitivity=91%; 95% confidence interval, 0.83-0.95; and specificity=80%; 95%
confidence interval, 0.75-0.83). CONCLUSIONS: Our findings provide quantitative
estimates of the claim that implementing vascular imaging at the referring
hospitals would result in significantly fewer futile transfers for EVT and a data
driven framework to inform transfer policies.
PMID- 28687642
TI - Government must take responsibility for air quality.
PMID- 28687643
TI - Cancer incidence attributable to lifestyle and environmental factors in Alberta
in 2012: summary of results.
AB - BACKGROUND: Estimates of the proportion of cancer cases that can be attributed to
modifiable risk factors are not available for Canada and, more specifically,
Alberta. The purpose of this study was to estimate the total proportion of cancer
cases in Alberta in 2012 that could be attributed to a set of 24 modifiable
lifestyle and environmental risk factors. METHODS: We estimated summary
population attributable risk estimates for 24 risk factors (smoking [both passive
and active], overweight and obesity, inadequate physical activity, diet
[inadequate fruit and vegetable consumption, inadequate fibre intake, excess red
and processed meat consumption, salt consumption, inadequate calcium and vitamin
D intake], alcohol, hormones [oral contraceptives and hormone therapy],
infections [Epstein-Barr virus, hepatitis B and C viruses, human papillomavirus,
Helicobacter pylori], air pollution, natural and artificial ultraviolet
radiation, radon and water disinfection by-products) by combining population
attributable risk estimates for each of the 24 factors that had been previously
estimated. To account for the possibility that individual cancer cases were the
result of a combination of multiple risk factors, we subtracted the population
attributable risk for the first factor from 100% and then applied the population
attributable risk for the second factor to the remaining proportion that was not
attributable to the first factor. We repeated this process in sequential order
for all relevant exposures. RESULTS: Overall, an estimated 40.8% of cancer cases
in Alberta in 2012 were attributable to modifiable lifestyle and environmental
risk factors. The largest proportion of cancers were estimated to be attributable
to tobacco smoking, physical inactivity and excess body weight. The summary
population attributable risk estimate was slightly higher among women (42.4%)
than among men (38.7%). INTERPRETATION: About 41% of cancer cases in Alberta may
be attributable to known modifiable lifestyle and environmental risk factors.
Reducing the prevalence of these factors in the Alberta population has the
potential to substantially reduce the provincial cancer burden.
PMID- 28687644
TI - Genome-Scale Model and Omics Analysis of Metabolic Capacities of Akkermansia
muciniphila Reveal a Preferential Mucin-Degrading Lifestyle.
AB - The composition and activity of the microbiota in the human gastrointestinal
tract are primarily shaped by nutrients derived from either food or the host.
Bacteria colonizing the mucus layer have evolved to use mucin as a carbon and
energy source. One of the members of the mucosa-associated microbiota is
Akkermansia muciniphila, which is capable of producing an extensive repertoire of
mucin-degrading enzymes. To further study the substrate utilization abilities of
A. muciniphila, we constructed a genome-scale metabolic model to test amino acid
auxotrophy, vitamin biosynthesis, and sugar-degrading capacities. The model
supported predictions were validated by in vitro experiments, which showed A.
muciniphila to be able to utilize the mucin-derived monosaccharides fucose,
galactose, and N-acetylglucosamine. Growth was also observed on N
acetylgalactosamine, even though the metabolic model did not predict this. The
uptake of these sugars, as well as the nonmucin sugar glucose, was enhanced in
the presence of mucin, indicating that additional mucin-derived components are
needed for optimal growth. An analysis of whole-transcriptome sequencing (RNA
Seq) comparing the gene expression of A. muciniphila grown on mucin with that of
the same bacterium grown on glucose confirmed the activity of the genes involved
in mucin degradation and revealed most of these to be upregulated in the presence
of mucin. The transcriptional response was confirmed by a proteome analysis,
altogether revealing a hierarchy in the use of sugars and reflecting the
adaptation of A. muciniphila to the mucosal environment. In conclusion, these
findings provide molecular insights into the lifestyle of A. muciniphila and
further confirm its role as a mucin specialist in the gut.IMPORTANCEAkkermansia
muciniphila is among the most abundant mucosal bacteria in humans and in a wide
range of other animals. Recently, A. muciniphila has attracted considerable
attention because of its capacity to protect against diet-induced obesity in
mouse models. However, the physiology of A. muciniphila has not been studied in
detail. Hence, we constructed a genome-scale model and describe its validation by
transcriptomic and proteomic approaches on bacterial cells grown on mucus and
glucose, a nonmucus sugar. The results provide detailed molecular insight into
the mucus-degrading lifestyle of A. muciniphila and further confirm the role of
this mucin specialist in producing propionate and acetate under conditions of the
intestinal tract.
PMID- 28687645
TI - Deficiency of RgpG Causes Major Defects in Cell Division and Biofilm Formation,
and Deficiency of LytR-CpsA-Psr Family Proteins Leads to Accumulation of Cell
Wall Antigens in Culture Medium by Streptococcus mutans.
AB - Streptococcus mutans is known to possess rhamnose-glucose polysaccharide (RGP), a
major cell wall antigen. S. mutans strains deficient in rgpG, encoding the first
enzyme of the RGP biosynthesis pathway, were constructed by allelic exchange. The
rgpG deficiency had no effect on growth rate but caused major defects in cell
division and altered cell morphology. Unlike the coccoid wild type, the rgpG
mutant existed primarily in chains of swollen, "squarish" dividing cells.
Deficiency of rgpG also causes significant reduction in biofilm formation (P <
0.01). Double and triple mutants with deficiency in brpA and/or psr, genes coding
for the LytR-CpsA-Psr family proteins BrpA and Psr, which were previously shown
to play important roles in cell envelope biogenesis, were constructed using the
rgpG mutant. There were no major differences in growth rates between the wild
type strain and the rgpG brpA and rgpG psr double mutants, but the growth rate of
the rgpG brpA psr triple mutant was reduced drastically (P < 0.001). Under
transmission electron microscopy, both double mutants resembled the rgpG mutant,
while the triple mutant existed as giant cells with multiple asymmetric septa.
When analyzed by immunoblotting, the rgpG mutant displayed major reductions in
cell wall antigens compared to the wild type, while little or no signal was
detected with the double and triple mutants and the brpA and psr single mutants.
These results suggest that RgpG in S. mutans plays a critical role in cell
division and biofilm formation and that BrpA and Psr may be responsible for
attachment of cell wall antigens to the cell envelope.IMPORTANCEStreptococcus
mutans, a major etiological agent of human dental caries, produces rhamnose
glucose polysaccharide (RGP) as the major cell wall antigen. This study provides
direct evidence that deficiency of RgpG, the first enzyme of the RGP biosynthesis
pathway, caused major defects in cell division and morphology and reduced biofilm
formation by S. mutans, indicative of a significant role of RGP in cell division
and biofilm formation in S. mutans These results are novel not only in S. mutans,
but also other streptococci that produce RGP. This study also shows that the LytR
CpsA-Psr family proteins BrpA and Psr in S. mutans are involved in attachment of
RGP and probably other cell wall glycopolymers to the peptidoglycan. In addition,
the results also suggest that BrpA and Psr may play a direct role in cell
division and biofilm formation in S. mutans This study reveals new potential
targets to develop anticaries therapeutics.
PMID- 28687646
TI - Aerobiological Stabilities of Different Species of Gram-Negative Bacteria,
Including Well-Known Biothreat Simulants, in Single-Cell Particles and Cell
Clusters of Different Compositions.
AB - The ability to perform controlled experiments with bioaerosols is a fundamental
enabler of many bioaerosol research disciplines. A practical alternative to using
hazardous biothreat agents, e.g., for detection equipment development and
testing, involves using appropriate model organisms (simulants). Several species
of Gram-negative bacteria have been used or proposed as biothreat simulants.
However, the appropriateness of different bacterial genera, species, and strains
as simulants is still debated. Here, we report aerobiological stability
characteristics of four species of Gram-negative bacteria (Pantoea agglomerans,
Serratia marcescens, Escherichia coli, and Xanthomonas arboricola) in single-cell
particles and cell clusters produced using four spray liquids (H2O, phosphate
buffered saline[PBS], spent culture medium[SCM], and a SCM-PBS mixture). E. coli
showed higher stability in cell clusters from all spray liquids than the other
species, but it showed similar or lower stability in single-cell particles. The
overall stability was higher in cell clusters than in single-cell particles. The
highest overall stability was observed for bioaerosols produced using SCM
containing spray liquids. A key finding was the observation that stability
differences caused by particle size or compositional changes frequently followed
species-specific patterns. The results highlight how even moderate changes to one
experimental parameter, e.g., bacterial species, spray liquid, or particle size,
can strongly affect the aerobiological stability of Gram-negative bacteria. Taken
together, the results highlight the importance of careful and informed selection
of Gram-negative bacterial biothreat simulants and also the accompanying particle
size and composition. The outcome of this work contributes to improved selection
of simulants, spray liquids, and particle size for use in bioaerosol
research.IMPORTANCE The outcome of this work contributes to improved selection of
simulants, spray liquids, and particle size for use in bioaerosol research. Taken
together, the results highlight the importance of careful and informed selection
of Gram-negative bacterial biothreat simulants and also the accompanying particle
size and composition. The results highlight how even moderate changes to one
experimental parameter, e.g., bacterial species, spray liquid, or particle size,
can strongly affect the aerobiological stability of Gram-negative bacteria. A key
finding was the observation that stability differences caused by particle size or
compositional changes frequently followed species-specific patterns.
PMID- 28687647
TI - The deep-sea bacterium Shewanella piezotolerans WP3 has two DMSO reductases in
distinct subcellular locations.
AB - Dimethyl sulfoxide (DMSO) acts as a substantial sink for dimethyl sulfide (DMS)
in deep waters and is therefore considered a potential electron acceptor
supporting abyssal ecosystems. Shewanella piezotolerans WP3 was isolated from
west Pacific deep-sea sediments, and two functional DMSO respiratory subsystems
are essential for maximum growth of WP3 under in situ conditions (4 degrees C/20
MPa). However, the relationship between these two subsystems and the electron
transport pathway underlying DMSO reduction by WP3 remain unknown. In this study,
both DMSO reductases (type I and type VI) in WP3 were found to be functionally
independent, despite their close evolutionary relationship. Moreover, immunogold
labeling of DMSO reductase subunits revealed that the type I DMSO reductase was
localized on the outer leaflet of the outer membrane, whereas the type VI DMSO
reductase was located within the periplasmic space. CymA, a cytoplasmic membrane
bound tetraheme c-type cytochrome, served as a preferential electron transport
protein for both the type I and type VI DMSO reductases, in which type VI
accepted electrons from CymA in a DmsE- and DmsF-independent manner. Based on
these results, we proposed a core electron transport model of DMSO reduction in
the deep-sea bacterium S. piezotolerans WP3. These results collectively suggest
that the possession of two sets of DMSO reductases with distinct subcellular
localizations might be an adaptive strategy for WP3 to achieve maximum DMSO
utilization in deep-sea environments.Importance: As the dominant methylated
sulfur compound in deep oceanic water, dimethyl sulfoxide (DMSO) has been
suggested to play an important role in the marine biogeochemical cycle of the
volatile anti-greenhouse gas dimethyl sulfide (DMS). Two sets of DMSO respiratory
systems in the deep-sea bacterium Shewanella piezotolerans WP3 have previously
been identified to mediate DMSO reduction under in situ conditions (4 degrees
C/20 MPa). Here, we report that the two DMSO reductases (type I and type VI) in
WP3 have distinct subcellular localizations, in which type I DMSO reductase is
localized to the exterior surface of the outer membrane, whereas type VI DMSO
reductase resides in the periplasmic space. A core electron transport model of
DMSO reduction in WP3 was constructed based on genetic and physiological data.
These results will contribute to a comprehensive understanding of the adaptation
mechanisms of anaerobic respiratory systems in benthic microorganisms.
PMID- 28687648
TI - Host Specificity of Flagellins from Segmented Filamentous Bacteria Affects Their
Patterns of Interaction with Mouse Ileal Mucosal Proteins.
AB - Segmented filamentous bacteria (SFB) are known modulators of the mammalian immune
system. Currently, the technology for investigating SFB culture in vitro is
immature, and as a result, the mechanisms of SFB colonization and immune
regulation are not yet fully elucidated. In this study, we investigated the gene
diversity and host specificity of SFB flagellin genes. The fliC1 and fliC2 genes
are relatively conserved, while the fliC3 and fliC4 genes are more variable,
especially at the central and C-terminal regions. Host specificity analysis
demonstrated that the fliC1 genes do not cluster together based on the host
organism, whereas the fliC3 and fliC4 genes were host specific at the nucleotide
and deduced amino acid levels. SFB flagellin protein expression in the ileum
mucosa and cecal contents was detected by using fluorescence in situ
hybridization (FISH) combined with immunohistochemical (IHC) analysis,
immunoblotting, and liquid chromatography-tandem mass spectrometry (LC-MS/MS).
Although the purified SFB FliC3 protein originating from both mouse and rat was
able to activate Toll-like receptor 5 (TLR5)-linked NF-kappaB signaling, no host
specificity was observed. Interestingly, the patterns of interaction with mouse
ileum mucosal proteins were different for mouse FliC3 (mFliC3) and rat FliC3
(rFliC3). Gene Ontology (GO) and KEGG analyses indicated that more adherence
related proteins interacted with mFliC3, while more lysosome- and proteolysis
related proteins interacted with rFliC3. In vitro degradation experiments
indicated that the stability of rFliC3 was lower than that of mFliC3 when they
were incubated with mouse ileum mucosal proteins. In summary, the gene diversity
and host specificity of SFB flagellin genes were investigated, and SFB flagellin
expression was detected in gut samples.IMPORTANCE Since SFB genomes contain only
one copy of each FliC gene, the diversity of FliC is representative of SFB strain
diversity. Currently, little is known regarding the diversity and specificity of
members of the group of SFB. The work presented herein demonstrates that select
SFB strains, exhibiting unique FliC patterns, are present in a variety of
mammalian hosts. SFB fliC genes were found to interact with a number of unique
targets, providing further evidence for SFB host selection. Together, this work
represents a major advancement in identifying SFB and delineating how members of
the group of SFB interact with the host. Future examination of FliC genes will
likely enhance our knowledge of intestinal colonization by the gut microbiota.
PMID- 28687649
TI - Imposed Environmental Stresses Facilitate Cell-Free Nanoparticle Formation by
Deinococcus radiodurans.
AB - The biological synthesis of metal nanoparticles has been examined in a wide range
of organisms, due to increased interest in green synthesis and environmental
remediation applications involving heavy metal ion contamination. Deinococcus
radiodurans is particularly attractive for environmental remediation involving
metal reduction, due to its high levels of resistance to radiation and other
environmental stresses. However, few studies have thoroughly examined the
relationships between environmental stresses and the resulting effects on
nanoparticle biosynthesis. In this work, we demonstrate cell-free nanoparticle
production and study the effects of metal stressor concentrations and identity,
temperature, pH, and oxygenation on the production of extracellular silver
nanoparticles by D. radiodurans R1. We also report the synthesis of bimetallic
silver and gold nanoparticles following the addition of a metal stressor (silver
or gold), highlighting how production of these particles is enabled through the
application of environmental stresses. Additionally, we found that both the
morphology and size of monometallic and bimetallic nanoparticles were dependent
on the environmental stresses imposed on the cells. The nanoparticles produced by
D. radiodurans exhibited antimicrobial activity comparable to that of pure silver
nanoparticles and displayed catalytic activity comparable to that of pure gold
nanoparticles. Overall, we demonstrate that biosynthesized nanoparticle
properties can be partially controlled through the tuning of applied
environmental stresses, and we provide insight into how their application may
affect nanoparticle production in D. radiodurans during bioremediation.IMPORTANCE
Biosynthetic production of nanoparticles has recently gained prominence as a
solution to rising concerns regarding increased bacterial resistance to
antibiotics and a desire for environmentally friendly methods of bioremediation
and chemical synthesis. To date, a range of organisms have been utilized for
nanoparticle formation. The extremophile D. radiodurans, which can withstand
significant environmental stresses and therefore is more robust for metal
reduction applications, has yet to be exploited for this purpose. Thus, this work
improves our understanding of the impact of environmental stresses on biogenic
nanoparticle morphology and composition during metal reduction processes in this
organism. This work also contributes to enhancing the controlled synthesis of
nanoparticles with specific attributes and functions using biological systems.
PMID- 28687650
TI - Parallel evolution of two clades of a major Atlantic endemic Vibrio
parahaemolyticus pathogen lineage by independent acquisition of related
pathogenicity islands.
AB - Shellfish-transmitted Vibrio parahaemolyticus infections have recently increased
from locations with historically low disease incidence, such as the Northeast
United States (US). This change coincided with a bacterial population shift
towards human pathogenic variants occurring in part through the introduction of
several Pacific native lineages (ST36, ST43 and ST636) to near-shore areas off
the Atlantic coast of the Northeast US. Concomitantly, ST631 emerged as a major
endemic pathogen. Phylogenetic trees of clinical and environmental isolates
indicated that two clades diverged from a common ST631 ancestor, and in each of
these clades, a human pathogenic variant evolved independently through
acquisition of distinct Vibrio pathogenicity islands (VPaI). These VPaI differ
from each other and bear little resemblance to hemolysin-containing VPaI from
isolates of the pandemic clonal complex. Clade I ST631 isolates either harbored
no hemolysins, or contained a chromosome I-inserted island we call VPaIbeta that
encodes a type three secretion system (T3SS2beta) typical of Trh hemolysin
producers. The more clinically prevalent and clonal ST631 clade II had an island
we call VPaIgamma that encodes both tdh and trh and that was inserted in
chromosome II. VPaIgamma was derived from VPaIbeta but with some additional
acquired elements in common with VPaI carried by pandemic isolates, exemplifying
the mosaic nature of pathogenicity islands. Genomics comparisons and amplicon
assays identified VPaIgamma-type islands containing tdh inserted adjacent to the
ure cluster in the three introduced Pacific and most other emergent lineages.
that collectively cause 67% of Northeast US infections as of 2016.IMPORTANCE The
availability of three different hemolysin genotypes in the ST631 lineage provided
a unique opportunity to employ genome comparisons to further our understanding of
the processes underlying pathogen evolution. The fact that two different
pathogenic clades arose in parallel from the same potentially benign lineage by
independent VPaI acquisition is surprising considering the historically low
prevalence of community members harboring VPaI in waters along the Northeast US
coast that could serve as the source of this material. This illustrates a
possible predisposition of some lineages to not only acquire foreign DNA but also
to become human pathogens. Whereas the underlying cause for the expansion of V.
parahaemolyticus lineages harboring VPaIgamma along the US Atlantic coast and
spread of this element to multiple lineages that underlies disease emergence is
not known, this work underscores the need to define the environment factors that
favor bacteria harboring VPaI in locations of emergent disease.
PMID- 28687651
TI - Shiga Toxin-Producing Serogroup O91 Escherichia coli Strains Isolated from Food
and Environmental Samples.
AB - Shiga toxin-producing Escherichia coli (STEC) strains of the O91:H21 serotype
have caused severe infections, including hemolytic-uremic syndrome. Strains of
the O91 serogroup have been isolated from food, animals, and the environment
worldwide but are not well characterized. We used a microarray and other
molecular assays to examine 49 serogroup O91 strains (environmental, food, and
clinical strains) for their virulence potential and phylogenetic relationships.
Most of the isolates were identified to be strains of the O91:H21 and O91:H14
serotypes, with a few O91:H10 strains and one O91:H9 strain being identified.
None of the strains had the eae gene, which codes for the intimin adherence
protein, and many did not have some of the genetic markers that are common in
other STEC strains. The genetic profiles of the strains within each serotype were
similar but differed greatly between strains of different serotypes. The genetic
profiles of the O91:H21 strains that we tested were identical or nearly identical
to those of the clinical O91:H21 strains that have caused severe diseases.
Multilocus sequence typing and clustered regularly interspaced short palindromic
repeat analyses showed that the O91:H21 strains clustered within the STEC 1
clonal group but the other O91 serotype strains were phylogenetically
diverse.IMPORTANCE This study showed that food and environmental O91:H21 strains
have similar genotypic profiles and Shiga toxin subtypes and are phylogenetically
related to the O91:H21 strains that have caused hemolytic-uremic syndrome,
suggesting that these strains may also have the potential to cause severe
illness.
PMID- 28687652
TI - High temporal and spatial variability of atmospheric-methane oxidation in Alpine
glacier-forefield soils.
AB - Glacier-forefield soils can provide a substantial sink for atmospheric CH4,
facilitated by aerobic methane-oxidizing bacteria (MOB). However, MOB activity,
abundance, and community structure may be affected by soil age, location in
different forefield landforms, and temporal fluctuations in soil-physical
parameters. We assessed spatial and temporal variability of atmospheric CH4
oxidation in an Alpine glacier forefield during the snow-free season 2013. We
quantified CH4 flux in soils of increasing age and in different landforms
(sandhill, terrace, floodplain) using soil-gas-profile and static flux-chamber
methods. To determine MOB abundance and community structure, we employed pmoA
gene-based quantitative PCR and targeted-amplicon sequencing. Uptake of CH4
increased in magnitude and decreased in variability with increasing soil age.
Sandhill soils exhibited CH4 uptake ranging from -0.03- -3.7 mg CH4 m-2 d-1
Floodplain and terrace soils exhibited smaller uptake and even intermittent CH4
emissions. Linear mixed-effect models indicated that soil age and landform were
dominating factors shaping CH4 flux, followed by cumulative rainfall (weighted
sum <= 4 d prior to sampling). Of 31 MOB operational taxonomic units retrieved,
~30% were potentially novel, and ~50% were affiliated with Upland Soil Clusters
gamma and alpha. The MOB community structures in floodplain and terrace soils
were nearly identical, but differed significantly from highly variable sandhill
soil communities. We conclude that soil age and landform modulate the soil CH4
sink strength in glacier forefields, and recent rainfall affects its short-term
variability. This should be taken into account when including this environment in
future CH4 inventories.Importance Oxidation of methane (CH4) in well-drained,
"upland" soils is an important mechanism for the removal of this potent
greenhouse gas from the atmosphere. It is largely mediated by aerobic, methane
oxidizing bacteria (MOB). Whereas there is abundant information on atmospheric
CH4 oxidation in mature upland soils, little is known about this important
function in young, developing soils such as those found in glacier forefields,
where new sediments are continuously exposed to the atmosphere as a result of
glacial retreat.In this field-based study we investigated spatial and temporal
variability of atmospheric CH4 oxidation and associated MOB communities in Alpine
glacier-forefield soils, aiming at better understanding factors that shape the
sink for atmospheric CH4 in this young soil ecosystem. The study contributes to
the knowledge on the dynamics of atmospheric CH4 oxidation in developing upland
soils, and represents a further step towards the inclusion of Alpine glacier
forefield soils in global CH4 inventories.
PMID- 28687654
TI - CORRECTION.
PMID- 28687653
TI - Identification of the ATPase Subunit of the Primary Maltose Transporter in the
Hyperthermophilic Anaerobe Thermotoga maritima.
AB - Thermotoga maritima is a hyperthermophilic anaerobic bacterium that produces
molecular hydrogen (H2) by fermentation. It catabolizes a broad range of
carbohydrates through the action of diverse ABC transporters. However, in T.
maritima and related species, highly similar genes with ambiguous annotation
obscure a precise understanding of genome function. In T. maritima, three
putative malK genes, all annotated as ATPase subunits, exhibited high identity to
each other. To distinguish between these genes, malK disruption mutants were
constructed by gene replacement, and the resulting mutant cell lines were
characterized. Only a disruption of malK3 produced a defect in maltose
catabolism. To verify that the mutant phenotype arose specifically from malK3
inactivation, the malK3 mutation was repaired by recombination, and maltose
catabolism was restored. This study demonstrates the importance of a maltose ABC
type transporter and its relationship to sugar metabolism in T.
maritimaIMPORTANCE The application and further development of a genetic system
was used here to investigate gene paralogs in the hyperthermophile Thermotoga
maritima The occurrence of three ABC transporter ATPase subunits all annotated as
malK was evaluated using a combination of genetic and bioinformatic approaches.
The results clarify the role of only one malK gene in maltose catabolism in a
nonmodel organism noted for fermentative hydrogen production.
PMID- 28687656
TI - Analysis of multisource data establishes wide-ranging antecedents of youth
suicide in England.
PMID- 28687655
TI - A Plastid Phosphatidylglycerol Lipase Contributes to the Export of Acyl Groups
from Plastids for Seed Oil Biosynthesis.
AB - The lipid composition of thylakoid membranes inside chloroplasts is conserved
from leaves to developing embryos. A finely tuned lipid assembly machinery is
required to build these membranes during Arabidopsis thaliana development.
Contrary to thylakoid lipid biosynthetic enzymes, the functions of most predicted
chloroplast lipid-degrading enzymes remain to be elucidated. Here, we explore the
biochemistry and physiological function of an Arabidopsis thylakoid membrane
associated lipase, PLASTID LIPASE1 (PLIP1). PLIP1 is a phospholipase A1 In vivo,
PLIP1 hydrolyzes polyunsaturated acyl groups from a unique chloroplast-specific
phosphatidylglycerol that contains 16:1 Delta3trans as its second acyl group.
Thus far, a specific function of this 16:1 Delta3trans -containing
phosphatidylglycerol in chloroplasts has remained elusive. The PLIP1 gene is
highly expressed in seeds, and plip1 mutant seeds contain less oil and exhibit
delayed germination compared with the wild type. Acyl groups released by PLIP1
are exported from the chloroplast, reincorporated into phosphatidylcholine, and
ultimately enter seed triacylglycerol. Thus, 16:1 Delta3trans uniquely labels a
small but biochemically active plastid phosphatidylglycerol pool in developing
Arabidopsis embryos, which is subject to PLIP1 activity, thereby contributing a
small fraction of the polyunsaturated fatty acids present in seed oil. We propose
that acyl exchange involving thylakoid lipids functions in acyl export from
plastids and seed oil biosynthesis.
PMID- 28687657
TI - Antigen Acquisition Enables Newly Arriving B Cells To Enter Ongoing Immunization
Induced Germinal Centers.
AB - Modern vaccines must be designed to generate long-lasting, high-affinity, and
broadly neutralizing Ab responses against pathogens. The diversity of B cell
clones recruited into germinal center (GC) responses is likely to be important
for the Ag-neutralization potential of the Ab-secreting cells and memory cells
generated upon immunization. However, the factors that influence the diversity of
B cell clones recruited into GCs are unclear. As recirculating naive Ag-specific
B cells arrive in Ag-draining secondary lymphoid organs, they may join the
ongoing GC response. However, the factors that limit their entry are not well
understood, and it is not known how that depends on the stage of the ongoing
follicular T cell and GC B cell response. In this article, we show that, in mice,
naive B cells have a limited window of time during which they can undergo Ag
driven activation and join ongoing immunization-induced GC responses. However,
preloading naive B cells with even a threshold-activating amount of Ag is
sufficient to rescue their entry into the GC response during its initiation,
peak, and contraction. Based on these results, we suggest that productive
acquisition of Ag may be one of the main factors limiting entry of new B cell
clones into ongoing immunization-triggered GC responses.
PMID- 28687658
TI - The Effect of Inhibitory Signals on the Priming of Drug Hapten-Specific T Cells
That Express Distinct Vbeta Receptors.
AB - Drug hypersensitivity involves the activation of T cells in an HLA allele
restricted manner. Because the majority of individuals who carry HLA risk alleles
do not develop hypersensitivity, other parameters must control development of the
drug-specific T cell response. Thus, we have used a T cell-priming assay and
nitroso sulfamethoxazole (SMX-NO) as a model Ag to investigate the activation of
specific TCR Vbeta subtypes, the impact of programmed death -1 (PD-1), CTL
associated protein 4 (CTLA4), and T cell Ig and mucin domain protein-3 (TIM-3)
coinhibitory signaling on activation of naive and memory T cells, and the ability
of regulatory T cells (Tregs) to prevent responses. An expansion of the TCR
repertoire was observed for nine Vbeta subtypes, whereas spectratyping revealed
that SMX-NO-specific T cell responses are controlled by public TCRs present in
all individuals alongside private TCR repertoires specific to each individual. We
proceeded to evaluate the extent to which the activation of these TCR Vbeta
restricted Ag-specific T cell responses is governed by regulatory signals.
Blockade of PD-L1/CTLA4 signaling dampened activation of SMX-NO-specific naive
and memory T cells, whereas blockade of TIM-3 produced no effect. Programmed
death-1, CTLA4, and TIM-3 displayed discrete expression profiles during drug
induced T cell activation, and expression of each receptor was enhanced on
dividing T cells. Because these receptors are also expressed on Tregs, Treg
mediated suppression of SMX-NO-induced T cell activation was investigated. Tregs
significantly dampened the priming of T cells. In conclusion, our findings
demonstrate that distinct TCR Vbeta subtypes, dysregulation of coinhibitory
signaling pathways, and dysfunctional Tregs may influence predisposition to
hypersensitivity.
PMID- 28687660
TI - Innate IFN-gamma-Producing Cells Developing in the Absence of IL-2 Receptor
Common gamma-Chain.
AB - IFN-gamma is known to be predominantly produced by lymphoid cells such as certain
subsets of T cells, NK cells, and other group 1 innate lymphoid cells. In this
study, we used IFN-gamma reporter mouse models to search for additional cells
capable of secreting this cytokine. We identified a novel and rare population of
nonconventional IFN-gamma-producing cells of hematopoietic origin that were
characterized by the expression of Thy1.2 and the lack of lymphoid, myeloid, and
NK lineage markers. The expression of IFN-gamma by this population was higher in
the liver and lower in the spleen. Furthermore, these cells were present in mice
lacking both the Rag2 and the common gamma-chain (gammac) genes (Rag2-/-gammac-/
), indicating their innate nature and their gammac cytokine independence. Rag2-/
gammac-/- mice are as resistant to Mycobacterium avium as Rag2-/- mice, whereas
Rag2-/- mice lacking IFN-gamma are more susceptible than either Rag2-/- or Rag2-/
gammac-/- These lineage-negative CD45+/Thy1.2+ cells are found within the
mycobacterially induced granulomatous structure in the livers of infected Rag2-/
gammac-/- animals and are adjacent to macrophages that expressed inducible NO
synthase, suggesting a potential protective role for these IFN-gamma-producing
cells. Accordingly, Thy1.2-specific mAb administration to infected Rag2-/-gammac
/- animals increased M. avium growth in the liver. Overall, our results
demonstrate that a population of Thy1.2+ non-NK innate-like cells present in the
liver expresses IFN-gamma and can confer protection against M. avium infection in
immunocompromised mice.
PMID- 28687659
TI - Neutrophils Induce Astroglial Differentiation and Migration of Human Neural Stem
Cells via C1q and C3a Synthesis.
AB - Inflammatory processes play a key role in pathophysiology of many neurologic
diseases/trauma, but the effect of immune cells and factors on
neurotransplantation strategies remains unclear. We hypothesized that cellular
and humoral components of innate immunity alter fate and migration of human
neural stem cells (hNSC). In these experiments, conditioned media collected from
polymorphonuclear leukocytes (PMN) selectively increased hNSC astrogliogenesis
and promoted cell migration in vitro. PMN were shown to generate C1q and C3a;
exposure of hNSC to PMN-synthesized concentrations of these complement proteins
promoted astrogliogenesis and cell migration. Furthermore, in vitro, Abs directed
against C1q and C3a reversed the fate and migration effects observed. In a proof
of-concept in vivo experiment, blockade of C1q and C3a transiently altered hNSC
migration and reversed astroglial fate after spinal cord injury. Collectively,
these data suggest that modulation of the innate/humoral inflammatory
microenvironment may impact the potential of cell-based therapies for recovery
and repair following CNS pathology.
PMID- 28687661
TI - A Systems Vaccinology Approach Reveals Temporal Transcriptomic Changes of Immune
Responses to the Yellow Fever 17D Vaccine.
AB - In this study, we used a systems vaccinology approach to identify temporal
changes in immune response signatures to the yellow fever (YF)-17D vaccine, with
the aim of comprehensively characterizing immune responses associated with
protective immunity. We conducted a cohort study in which 21 healthy subjects in
China were administered one dose of the YF-17D vaccine; PBMCs were collected at 0
h and then at 4 h and days 1, 2, 3, 5, 7, 14, 28, 84, and 168 postvaccination,
and analyzed by transcriptional profiling and immunological assays. At 4 h
postvaccination, genes associated with innate cell differentiation and cytokine
pathways were dramatically downregulated, whereas receptor genes were
upregulated, compared with their baseline levels at 0 h. Immune response pathways
were primarily upregulated on days 5 and 7, accompanied by the upregulation of
the transcriptional factors JUP, STAT1, and EIF2AK2. We also observed robust
activation of innate immunity within 2 d postvaccination and a durable adaptive
response, as assessed by transcriptional profiling. Coexpression network analysis
indicated that lysosome activity and lymphocyte proliferation were associated
with dendritic cell (DC) and CD4+ T cell responses; FGL2, NFAM1, CCR1, and
TNFSF13B were involved in these associations. Moreover, individuals who were
baseline-seropositive for Abs against another flavivirus exhibited significantly
impaired DC, NK cell, and T cell function in response to YF-17D vaccination.
Overall, our findings indicate that YF-17D vaccination induces a prompt innate
immune response and DC activation, a robust Ag-specific T cell response, and a
persistent B cell/memory B cell response.
PMID- 28687662
TI - Virus-Triggered ATP Release Limits Viral Replication through Facilitating IFN
beta Production in a P2X7-Dependent Manner.
AB - Accumulating evidence shows that innate immune responses are associated with
extracellular nucleotides, particularly ATP. In this article, we demonstrate
extensive protection of ATP/P2X7 signaling in a host against viral infection.
Interestingly, we observed a significant increase in ATP as a danger signal in
vesicular stomatitis virus (VSV)-infected cell supernatant and VSV-infected mice
in an exocytosis- and pannexin channel-dependent manner. Furthermore,
extracellular ATP reduces the replication of VSV, Newcastle disease virus, murine
leukemia virus, and HSV in vivo and in vitro through the P2X7 receptor.
Meanwhile, ATP significantly increases IFN-beta expression in a concentration-
and time-dependent manner. Mechanistically, ATP facilitates IFN-beta secretion
through P38/JNK/ATF-2 signaling pathways, which are crucial in promoting
antiviral immunity. Taken together, these results demonstrate the protective role
of extracellular ATP and P2X7 in viral infection and suggest a potential
therapeutic role for ATP/P2X7 in viral diseases.
PMID- 28687663
TI - A module for Rac temporal signal integration revealed with optogenetics.
AB - Sensory systems use adaptation to measure changes in signaling inputs rather than
absolute levels of signaling inputs. Adaptation enables eukaryotic cells to
directionally migrate over a large dynamic range of chemoattractant. Because of
complex feedback interactions and redundancy, it has been difficult to define the
portion or portions of eukaryotic chemotactic signaling networks that generate
adaptation and identify the regulators of this process. In this study, we use a
combination of optogenetic intracellular inputs, CRISPR-based knockouts, and
pharmacological perturbations to probe the basis of neutrophil adaptation. We
find that persistent, optogenetically driven phosphatidylinositol (3,4,5)
trisphosphate (PIP3) production results in only transient activation of Rac, a
hallmark feature of adaptive circuits. We further identify the guanine nucleotide
exchange factor P-Rex1 as the primary PIP3-stimulated Rac activator, whereas
actin polymerization and the GTPase-activating protein ArhGAP15 are essential for
proper Rac turnoff. This circuit is masked by feedback and redundancy when
chemoattractant is used as the input, highlighting the value of probing signaling
networks at intermediate nodes to deconvolve complex signaling cascades.
PMID- 28687664
TI - Tubulin glycylation controls primary cilia length.
AB - As essential components of the eukaryotic cytoskeleton, microtubules fulfill a
variety of functions that can be temporally and spatially controlled by tubulin
posttranslational modifications. Tubulin glycylation has so far been mostly found
on motile cilia and flagella, where it is involved in the stabilization of the
axoneme. In contrast, barely anything is known about the role of glycylation in
primary cilia because of limitations in detecting this modification in these
organelles. We thus developed novel glycylation-specific antibodies with which we
detected glycylation in many primary cilia. Glycylation accumulates in primary
cilia in a length-dependent manner, and depletion or overexpression of
glycylating enzymes modulates the length of primary cilia in cultured cells. This
strongly suggests that glycylation is essential for the homeostasis of primary
cilia, which has important implications for human disorders related to primary
cilia dysfunctions, such as ciliopathies and certain types of cancer.
PMID- 28687665
TI - Mutation of the alpha-tubulin Tuba1a leads to straighter microtubules and
perturbs neuronal migration.
AB - Brain development involves extensive migration of neurons. Microtubules (MTs) are
key cellular effectors of neuronal displacement that are assembled from
alpha/beta-tubulin heterodimers. Mutation of the alpha-tubulin isotype TUBA1A is
associated with cortical malformations in humans. In this study, we provide
detailed in vivo and in vitro analyses of Tuba1a mutants. In mice carrying a
Tuba1a missense mutation (S140G), neurons accumulate, and glial cells are
dispersed along the rostral migratory stream in postnatal and adult brains. Live
imaging of Tuba1a-mutant neurons revealed slowed migration and increased neuronal
branching, which correlated with directionality alterations and perturbed nucleus
centrosome (N-C) coupling. Tuba1a mutation led to increased straightness of newly
polymerized MTs, and structural modeling data suggest a conformational change in
the alpha/beta-tubulin heterodimer. We show that Tuba8, another alpha-tubulin
isotype previously associated with cortical malformations, has altered function
compared with Tuba1a. Our work shows that Tuba1a plays an essential,
noncompensated role in neuronal saltatory migration in vivo and highlights the
importance of MT flexibility in N-C coupling and neuronal-branching regulation
during neuronal migration.
PMID- 28687666
TI - Domain-specific control of germ cell polarity and migration by multifunction Tre1
GPCR.
AB - The migration of primordial germ cells (PGCs) from their place of origin to the
embryonic gonad is an essential reproductive feature in many animal species. In
Drosophila melanogaster, a single G protein-coupled receptor, Trapped in endoderm
1 (Tre1), mediates germ cell polarization at the onset of active migration and
directs subsequent migration of PGCs through the midgut primordium. How these
different aspects of cell behavior are coordinated through a single receptor is
not known. We demonstrate that two highly conserved domains, the E/N/DRY and
NPxxY motifs, have overlapping and unique functions in Tre1. The Tre1-NRY domain
via G protein signaling is required for reading and responding to guidance and
survival cues controlled by the lipid phosphate phosphatases Wunen and Wunen2. In
contrast, the Tre1-NPIIY domain has a separate role in Rho1- and E-cadherin
mediated polarization at the initiation stage independent of G protein signaling.
We propose that this bifurcation of the Tre1 G protein-coupled receptor signaling
response via G protein-dependent and independent branches enables distinct
spatiotemporal regulation of germ cell migration.
PMID- 28687668
TI - Tubulin isotype specificity in neuronal migration: Tuba8 can't fill in for
Tuba1a.
AB - Several tubulin isotypes, including Tuba1a, are associated with brain
malformations. In this issue, Belvindrah et al. (2017. J. Cell Biol.
https://doi.org/10.1083/jcb.201607074) show that Tuba1a and Tuba8 differentially
regulate microtubule organization in neurons, and they provide insights into the
mechanisms by which Tuba1a mutations disrupt adult mouse brain morphology.
PMID- 28687667
TI - Membrane tension controls adhesion positioning at the leading edge of cells.
AB - Cell migration is dependent on adhesion dynamics and actin cytoskeleton
remodeling at the leading edge. These events may be physically constrained by the
plasma membrane. Here, we show that the mechanical signal produced by an increase
in plasma membrane tension triggers the positioning of new rows of adhesions at
the leading edge. During protrusion, as membrane tension increases, velocity
slows, and the lamellipodium buckles upward in a myosin II-independent manner.
The buckling occurs between the front of the lamellipodium, where nascent
adhesions are positioned in rows, and the base of the lamellipodium, where a
vinculin-dependent clutch couples actin to previously positioned adhesions. As
membrane tension decreases, protrusion resumes and buckling disappears, until the
next cycle. We propose that the mechanical signal of membrane tension exerts
upstream control in mechanotransduction by periodically compressing and relaxing
the lamellipodium, leading to the positioning of adhesions at the leading edge of
cells.
PMID- 28687669
TI - Atrioventricular Nodal Reentrant Tachycardia in Patients With Congenital Heart
Disease: Outcome After Catheter Ablation.
AB - BACKGROUND: The relationship of atrioventricular nodal reentrant tachycardia to
congenital heart disease (CHD) and the outcome of catheter ablation in this
population have not been studied adequately. METHODS AND RESULTS: A multicenter
retrospective study was performed on patients with CHD who had atrioventricular
nodal reentrant tachycardia and were treated with catheter ablation. There were
109 patients (61 women), aged 22.1+/-13.4 years. The majority, 86 of 109 (79%),
had CHD resulting in right heart pressure or volume overload. Patients were
divided into 2 groups: group A (n=51) with complex CHD and group B (n=58) with
simple CHD. There were no significant differences between groups in patients'
growth parameters, use of 3-dimensional imaging, and type of ablation
(radiofrequency versus cryoablation). Procedure times (251+/-117 versus 174+/-94
minutes; P=0.0006) and fluoroscopy times (median 20.8 versus 16.6 minutes;
P=0.037) were longer in group A versus group B. There were significant
differences between groups in the acute success of ablation (82% versus 97%;
P=0.04), risk of atrioventricular block (14 versus 0%; P=0.004), and need for
chronic pacing (10% versus 0%; P=0.008). There was no permanent atrioventricular
block in patients who underwent cryoablation. After 3.2+/-2.7 years of follow-up,
long-term success was 86% in group A and 100% in group B (P=0.004). CONCLUSIONS:
Atrioventricular nodal reentrant tachycardia can complicate the course of
patients with CHD. This study demonstrates that the outcome of catheter ablation
is favorable in patients with simple CHD. Patients with complex CHD have
increased risk of procedural failure and atrioventricular block.
PMID- 28687670
TI - Stand-Alone Pulmonary Vein Isolation Versus Pulmonary Vein Isolation With
Additional Substrate Modification as Index Ablation Procedures in Patients With
Persistent and Long-Standing Persistent Atrial Fibrillation: The Randomized
Alster-Lost-AF Trial (Ablation at St. Georg Hospital for Long-Standing Persistent
Atrial Fibrillation).
AB - BACKGROUND: Pulmonary vein isolation (PVI) for persistent atrial fibrillation is
associated with limited success rates and often requires multiple procedures to
maintain stable sinus rhythm. In the prospective and randomized Alster-Lost-AF
trial (Ablation at St. Georg Hospital for Long-Standing Persistent Atrial
Fibrillation), we sought to assess, in patients with symptomatic persistent or
long-standing persistent atrial fibrillation, the outcomes of initial ablative
strategies comprising either stand-alone PVI (PVI-only approach) or a stepwise
approach of PVI followed by complex fractionated atrial electrogram ablation and
linear ablation (Substrate-modification approach). METHODS AND RESULTS: Patients
were randomized 1:1 to stand-alone PVI or PVI plus substrate modification. The
primary study end point was freedom from recurrence of any atrial
tachyarrhythmia, outside a 90-day blanking period, at 12 months. A total of 124
patients were enrolled, with 118 patients included in the analysis (61 in the PVI
only group, 57 in the Substrate-modification group). Atrial tachyarrhythmias
recurred in 28 PVI-only group patients and 24 Substrate-modification group
patients, for 1-year freedom from tachyarrhythmia recurrence after a single
ablation procedure of 54% (95% confidence interval, 43%-68%) in the PVI-only and
57% (95% confidence interval, 46%-72%) in the Substrate-modification group
(P=0.86). Twenty-four patients in the PVI-only group (39%) and 18 in the
Substrate-modification group (32%) were without arrhythmia recurrence and off
antiarrhythmic drug therapy at the end of the 12-month follow-up. CONCLUSIONS: In
patients with persistent and long-standing persistent atrial fibrillation, no
significant difference was observed in 12-month freedom from atrial
tachyarrhythmias between an index ablative approach of stand-alone PVI and a
stepwise approach of PVI plus complex fractionated atrial electrogram and linear
ablation. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique
identifier: NCT00820625.
PMID- 28687672
TI - Where to Throw That Shoe? Catheter Ablation of Atrioventricular Nodal Reentrant
Tachycardia in Congenital Heart Disease.
PMID- 28687671
TI - Tachycardia-Induced J-Wave Changes in Patients With and Without Idiopathic
Ventricular Fibrillation.
AB - BACKGROUND: To know the underlying mechanisms of J waves, the response to atrial
pacing was studied in patients with idiopathic ventricular fibrillation (IVF) and
patients with non-IVF. METHODS AND RESULTS: In 8 patients with IVF, the J-wave
amplitude was measured before, during, and after atrial pacing. All patients had
episodes of ventricular fibrillation without structural heart disease. The
responses of J waves were compared with those of the 17 non-IVF control subjects
who revealed J waves but no history of cardiac arrest and underwent
electrophysiological study. The IVF patients were younger than the non-IVF
patients (28+/-10 versus 52+/-14 years, respectively; P=0.002) and had larger J
waves with more extensive distribution. J waves decreased from 0.35+/-0.26 to
0.22+/-0.23 mV (P=0.025) when the RR intervals were shortened from 782+/-88 to
573+/-162 ms (P=0.001). A decrease (>=0.05 mV) in the J-wave amplitude was
observed in 6 of the 8 patients. In addition, 1 patient showed a distinct
reduction of J waves in the unipolar epicardial leads. In contrast, J waves were
augmented in the 17 non-IVF subjects from 0.27+/-0.09 to 0.38+/-0.10 mV
(P<0.001): augmented in 9 and unchanged in the 8 subjects. The different response
patterns of J waves to rapid pacing suggest different mechanisms: early
repolarization in IVF patients and conduction delay in non-IVF patients.
CONCLUSIONS: The response to atrial pacing was different between the IVF and non
IVF patients, which suggests the presence of different mechanisms for the genesis
of J waves.
PMID- 28687673
TI - What's New in the Journal.
PMID- 28687676
TI - Mildred S. Dresselhaus (1930-2017): A fierce force of harmony.
PMID- 28687675
TI - Two dynamin-like proteins stabilize FtsZ rings during Streptomyces sporulation.
AB - During sporulation, the filamentous bacteria Streptomyces undergo a massive cell
division event in which the synthesis of ladders of sporulation septa convert
multigenomic hyphae into chains of unigenomic spores. This process requires
cytokinetic Z-rings formed by the bacterial tubulin homolog FtsZ, and the
stabilization of the newly formed Z-rings is crucial for completion of septum
synthesis. Here we show that two dynamin-like proteins, DynA and DynB, play
critical roles in this process. Dynamins are a family of large, multidomain
GTPases involved in key cellular processes in eukaryotes, including vesicle
trafficking and organelle division. Many bacterial genomes encode dynamin-like
proteins, but the biological function of these proteins has remained largely
enigmatic. Using a cell biological approach, we show that the two Streptomyces
dynamins specifically localize to sporulation septa in an FtsZ-dependent manner.
Moreover, dynamin mutants have a cell division defect due to the decreased
stability of sporulation-specific Z-rings, as demonstrated by kymographs derived
from time-lapse images of FtsZ ladder formation. This defect causes the premature
disassembly of individual Z-rings, leading to the frequent abortion of septum
synthesis, which in turn results in the production of long spore-like
compartments with multiple chromosomes. Two-hybrid analysis revealed that the
dynamins are part of the cell division machinery and that they mediate their
effects on Z-ring stability during developmentally controlled cell division via a
network of protein-protein interactions involving DynA, DynB, FtsZ, SepF, SepF2,
and the FtsZ-positioning protein SsgB.
PMID- 28687674
TI - Anti-inflammatory omega-3 endocannabinoid epoxides.
AB - Clinical studies suggest that diets rich in omega-3 polyunsaturated fatty acids
(PUFAs) provide beneficial anti-inflammatory effects, in part through their
conversion to bioactive metabolites. Here we report on the endogenous production
of a previously unknown class of omega-3 PUFA-derived lipid metabolites that
originate from the crosstalk between endocannabinoid and cytochrome P450 (CYP)
epoxygenase metabolic pathways. The omega-3 endocannabinoid epoxides are derived
from docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) to form
epoxyeicosatetraenoic acid-ethanolamide (EEQ-EA) and epoxydocosapentaenoic acid
ethanolamide (EDP-EA), respectively. Both EEQ-EAs and EDP-EAs are endogenously
present in rat brain and peripheral organs as determined via targeted lipidomics
methods. These metabolites were directly produced by direct epoxygenation of the
omega-3 endocannabinoids, docosahexanoyl ethanolamide (DHEA) and eicosapentaenoyl
ethanolamide (EPEA) by activated BV-2 microglial cells, and by human CYP2J2.
Neuroinflammation studies revealed that the terminal epoxides 17,18-EEQ-EA and
19,20-EDP-EA dose-dependently abated proinflammatory IL-6 cytokines while
increasing anti-inflammatory IL-10 cytokines, in part through cannabinoid
receptor-2 activation. Furthermore the omega-3 endocannabinoid epoxides 17,18-EEQ
EA and 19,20-EDP-EA exerted antiangiogenic effects in human microvascular
endothelial cells (HMVEC) and vasodilatory actions on bovine coronary arteries
and reciprocally regulated platelet aggregation in washed human platelets. Taken
together, the omega-3 endocannabinoid epoxides' physiological effects are
mediated through both endocannabinoid and epoxyeicosanoid signaling pathways. In
summary, the omega-3 endocannabinoid epoxides are found at concentrations
comparable to those of other endocannabinoids and are expected to play critical
roles during inflammation in vivo; thus their identification may aid in the
development of therapeutics for neuroinflammatory and cerebrovascular diseases.
PMID- 28687677
TI - A community-based motivational personalised lifestyle intervention to reduce BMI
in obese adolescents: results from the Healthy Eating and Lifestyle Programme
(HELP) randomised controlled trial.
AB - OBJECTIVE: Approximately 7% of children and young people aged 5-15 years in the
UK have obesity at a level likely to be associated with comorbidities. The
majority of multicomponent lifestyle programmes have limited applicability and
generalisability for British adolescents.The Healthy Eating and Lifestyle
Programme (HELP) was a specific adolescent-focused intervention, designed for
obese 12 to 18-year-olds seeking help to manage their weight. Participants were
randomised to the 12-session HELP intervention or standard care. The primary
outcome was difference in mean body mass index (BMI) (kg/m2) between groups at
week 26 adjusted for baseline BMI, age and sex. SUBJECTS: 174 subjects were
randomised (87 in each arm), of whom 145 (83%) provided primary outcome data at
week 26. RESULTS: At week 26 there were no significant effects of the
intervention on BMI (mean change in BMI 0.18 kg/m2 for the intervention arm, 0.25
kg/m2 for the control arm; adjusted difference between groups: -0.11 kg/m2 (95%
CI -0.62 to 0.40), p=0.7). At weeks 26 and 52 there were no significant
differences between groups in any secondary outcomes. CONCLUSION: At minimum this
study reinforces the need for higher level, structured interventions to tackle
the growing public health burden of obesity in the UK and internationally.The
HELP intervention was no more effective than a single educational session for
reducing BMI in a community sample of obese adolescents.Further work is needed to
understand how weight management programmes can be delivered effectively to young
people from diverse and deprived backgrounds in which childhood obesity is
common. The study has significant implications in terms of informing public
health interventions to tackle childhood obesity. TRIAL REGISTRATION NUMBER:
ISRCTN: ISRCTN99840111.
PMID- 28687679
TI - Targeting toll-like receptor 7/8 improves host anti-infective response in
alcoholic cirrhosis.
PMID- 28687678
TI - Occupational exposure to pesticides are associated with fixed airflow obstruction
in middle-age.
AB - RATIONALE: Population-based studies have found evidence of a relationship between
occupational exposures and Chronic Obstructive Pulmonary Disease (COPD), but
these studies are limited by the use of prebronchodilator spirometry.
Establishing this link using postbronchodilator is critical, because occupational
exposures are a modifiable risk factor for COPD. OBJECTIVES: To investigate the
associations between occupational exposures and fixed airflow obstruction using
postbronchodilator spirometry. METHODS: One thousand three hundred and thirty
five participants were included from 2002 to 2008 follow-up of the Tasmanian
Longitudinal Health Study (TAHS). Spirometry was performed and lifetime work
history calendars were used to collect occupational history. ALOHA plus Job
Exposure Matrix was used to assign occupational exposure, and defined as ever
exposed and cumulative exposure unit (EU)-years. Fixed airflow obstruction was
defined by postbronchodilator FEV1/FVC <0.7 and the lower limit of normal (LLN).
Multinomial logistic regressions were used to investigate potential associations
while controlling for possible confounders. RESULTS: Ever exposure to biological
dust (relative risk (RR)=1.58, 95% CI 1.01 to 2.48), pesticides (RR=1.74,95% CI
1.00 to 3.07) and herbicides (RR=2.09,95% CI 1.18 to 3.70) were associated with
fixed airflow obstruction. Cumulative EU-years to all pesticides (RR=1.11,95% CI
1.00 to 1.25) and herbicides (RR=1.15,95% CI 1.00 to 1.32) were also associated
with fixed airflow obstruction. In addition, all pesticides exposure was
consistently associated with chronic bronchitis and symptoms that are consistent
with airflow obstruction. Ever exposure to mineral dust, gases/fumes and vapours,
gases, dust or fumes were only associated with fixed airflow obstruction in non
asthmatics only. CONCLUSIONS: Pesticides and herbicides exposures were associated
with fixed airflow obstruction and chronic bronchitis. Biological dust exposure
was also associated with fixed airflow obstruction in non-asthmatics. Minimising
occupational exposure to these agents may help to reduce the burden of COPD.
PMID- 28687680
TI - Massive gastrointestinal bleeding after transjugular intrahepatic portosystemic
shunt (TIPS).
PMID- 28687681
TI - Communication changes in Parkinson's disease.
AB - This review looks at the nature and impact of communication changes in
Parkinson's disease, approaches to assessment and directions for intervention.
This is especially important since medical and surgical interventions that help
limb movement are largely ineffective, or even detrimental, for speech. Most
people with Parkinson's disease notice changes to their communication. Voice
alters early on-even in the prodromal stage. Later, articulation may impair
intelligibility further. These changes impact on mood and social participation.
However, a full characterisation of communication changes in Parkinson's must
acknowledge that changes are far more pervasive and varied than a quiet voice.
Communication is affected by marked dysprosody, cognitive-linguistic impairment,
alterations to social interaction and pragmatics. Changes entail not just
expressive elements but also receptive. A comprehensive evaluation of potential
communication challenges faced by people with Parkinson's disease must cover all
these aspects. Similarly, interventions that ignore the breadth and depth of
changes will always remain incomplete.
PMID- 28687682
TI - Bilateral interstitial keratitis with anterior stromal infiltrates associated
with reactive arthritis.
AB - A previously healthy 48-year-old man presented with a 1-week history of migrating
polyarthropathy preceded by a viral illness, dysuria and bilateral red eyes.
Ocular examination revealed anterior and interstitial stromal keratitis. He was
systemically well but had raised erythrocyte sedimentation rate and C reactive
protein and was positive for human leucocyte antigen B27 on extensive infective,
rheumatological and autoimmune investigations. Although the exact triggering
pathogen was not identified, clinical findings were consistent with reactive
arthritis. Bilateral interstitial keratitis is a rare manifestation of reactive
arthritis which, along with the anterior stromal keratitis, responded well to
topical prednisolone sodium phosphate 0.5%. Systemic joint symptoms improved on
oral sulfasalazine, non-steroid anti-inflammatory agent and low-dose
prednisolone.
PMID- 28687683
TI - Substantial harm associated with failure of chronic paediatric central venous
access devices.
AB - Central venous access devices (CVADs) form an important component of modern
paediatric healthcare, especially for children with chronic health conditions
such as cancer or gastrointestinal disorders. However device failure and
complications rates are high.Over 21/2 years, a child requiring parenteral
nutrition and associated vascular access dependency due to 'short gut syndrome'
(intestinal failure secondary to gastroschisis and resultant significant bowel
resection) had ten CVADs inserted, with ninesubsequently failing. This resulted
in multiple anaesthetics, invasive procedures, injuries, vascular depletion,
interrupted nutrition, delayed treatment and substantial healthcare costs. A
conservative estimate of the institutional costs for each insertion, or rewiring,
of her tunnelled CVAD was $A10 253 (2016 Australian dollars).These complications
and device failures had significant negative impact on the child and her family.
Considering the commonality of conditions requiring prolonged vascular access,
these failures also have a significant impact on international health service
costs.
PMID- 28687684
TI - Transient neonatal hypercalcaemia secondary to excess maternal vitamin D intake:
too much of a good thing.
AB - We report a case of transient neonatal hypercalcaemia secondary to excess
maternal vitamin D intake in pregnancy. Vitamin D insufficiency and deficiency in
pregnancy are associated with adverse pregnancy outcomes, but there is no
definite benefit to supplementation. The Royal College of Obstetrics and
Gynaecology recommends routine supplementation with vitamin D3 400 IU/day, but
higher dose preparations usually recommended for the treatment of vitamin D
deficiency are readily available over the counter. This case highlights the risks
of excess supplementation, especially at higher doses and in women without
evidence of vitamin D deficiency. The amount used in this case was at the upper
end of the generally accepted safe dose range, but still less than that commonly
recognised to cause problems. Neonatal hypercalcaemia is a potentially serious
condition. The current local or national recommendations for vitamin D
supplementation and the possible adverse effects of excess vitamin D consumption
should be clearly communicated to pregnant women.
PMID- 28687685
TI - Sternoclavicular joint osteophytosis: a difficult diagnosis to swallow.
AB - Unexplained dysphagia requires prompt investigation to rule out a possible
underlying malignancy. We describe the case of a 60-year-old man who presented to
his family practitioner with a 1-year history of increasing dysphagia with
associated pain over the front of his chest. He was referred on to an ear, nose
and throat specialist where no obvious laryngeal pathology was found at direct
laryngoscopy, but an 'indentation' of the right anterior larynx, which increased
with external pressure on the sternoclavicular joint (SCJ), was noted. A
subsequent CT scan of his neck demonstrated osteoarthritis of the right SCJ with
an abnormally large posterior osteophyte. The patient was subsequently referred
on to an orthopaedic surgeon specialising in SCJ surgery and underwent an
arthroscopic excision of his right SCJ. Soon after surgery, the patient's
dysphagia had settled and his symptoms remain resolved 1 year post surgery.
PMID- 28687686
TI - Isolated insulin-derived amyloidoma of the breast.
AB - Isolated amyloidomas derived from insulin are extremely rare, and there is only
one reported case to date of insulin-derived amyloidoma in the breast.We present
the case of a 36-year-old woman reporting a lump in the right breast. It was
clinically assessed as a probable fibroadenoma but was removed surgically given
the size of the lesion. On histological analysis, the lesion had features
consistent with amyloid. Further investigations showed the amyloid to be derived
from insulin. The lump was removed in its entirety, and the patient made a full
recovery.
PMID- 28687687
TI - Use of low-dose thrombolytics for treatment of intracardiac thrombus and massive
pulmonary embolus after aborted liver transplant leads to recovery of right
ventricular function and redo liver transplantation.
AB - This is a 61-year-old man with end-stage liver disease who experienced cardiac
arrest secondary to a massive pulmonary embolus and intracardiac thrombus during
cannulation for veno-venous extracorporeal membrane oxygenation (ECMO) in
preparation for orthotopic liver transplantation (OLT). Surgery was aborted and
the patient was taken back to the intensive care unit in cardiogenic shock on
multiple vasopressors. The patient was unresponsive to heparin bolus and too high
risk for systemic thrombolytics or embolectomy. He was ultimately treated with 12
mg total of alteplase through his pulmonary artery catheter over 3 hours. He had
subsequent resolution of his cardiogenic shock and proceeded with successful
liver transplantation 5 days after his initial event without any bleeding
complications. Low-dose thrombolytic therapy in the setting of absolute
contraindications to thrombolysis allowed for recovery of cardiac function and,
ultimately redo OLT in a patient with otherwise little hope of survival.
PMID- 28687688
TI - Contribution of arterial spin-labelling MRI in a case with immune reconstitution
inflammatory syndrome.
AB - Central nervous system immune reconstitution inflammatory syndrome (CNS-IRIS),
which occurs most often in HIV-infected patients, is an exacerbation of
inflammatory reactions related to opportunistic infections as well as primary CNS
malignancies both of which mostly occur in HIV-infected patients. However,
differential diagnoses are challenging both clinically and radiologically. We
describe a patient with CNS-IRIS due to toxoplasmosis whose 11C-methionine uptake
suggested lymphoma but whose arterial spin-labelling MRI led to the correct
diagnosis.
PMID- 28687689
TI - Persistent sacral chloroma in refractory acute myelogenous leukaemia.
AB - Acute myelogenous leukaemia (AML) is a clonal process involving the myeloid
subgroup of white blood cells. Chloromas, or myeloid sarcomas, are masses of
myeloid leukaemic cells and are a unique aspect of AML. This case involves a 14
year-old boy with AML who presented with multiple chloromas at diagnosis. The
patient's extra-calvarial masses and bone marrow involvement responded to
chemotherapy; however, his sacral epidural chloromas persisted despite four
courses of chemotherapy. The central nervous system, bone marrow and testes have
been known to be sanctuary sites for AML. This case illustrates that the sacral
spinal canal may potentially be a sanctuary site for the disease process also.
PMID- 28687690
TI - Cryptococcal meningitis causing obstructive hydrocephalus in a patient on
fingolimod.
AB - Cryptococcosis is a recognised opportunistic infection in immunocompromised
patients. The long-term adverse effect profile of fingolimod, an immunomodulating
agent approved for use in multiple sclerosis in 2010, is only just emerging. We
report the first case to our knowledge of a patient presenting with obstructive
hydrocephalus secondary to cryptococcal meningitis in the setting of fingolimod
therapy. Extensive posterior fossa leptomeningeal inflammation with associated
cerebellar oedema resulted in effacement of the fourth ventricle and obstructive
hydrocephalus requiring urgent ventriculostomy. Induction, consolidative and
maintenance antifungal therapy was prescribed and subsequent conversion to a
ventriculoperitoneal shunt was successful in relieving the patient's
ventriculomegaly. Awareness of these rare, novel and life-threatening
complications of fingolimod-associated immunocompromise is critical as the use of
such drugs is expected to rise.
PMID- 28687691
TI - Vascularisation of the anterior lens capsule in an eye with excellent visual
acuity.
AB - A 53-year-old phakic female with a history of nanophthalmos and hyperopia was
incidentally found to have unilateral neovascularisation on the left
inferoanterior lens surface on routine review for ocular hypertension.
PMID- 28687692
TI - Diencephalic syndrome: a rare cause of failure to thrive.
AB - Timely diagnosis of diencephalic syndrome is not often the case for patients
presenting with failure to thrive (FTT) because of its rarity and lack of
specific symptoms. Herein, we report two cases of diencephalic syndrome (2-year
old girl and 10-month-old boy) presenting with severe emaciation. Both patients
had histories of poor weight gain for months despite having good appetites prior
to diagnosis. Initial work-up did not reveal the diagnosis. Horizontal nystagmus
was noted in both patients: by a neurologist in the first patient and by a family
member in the second patient. MRI of the brain showed large suprasellar mass and
pilocytic astrocytoma was confirmed by pathology in each case. The patients were
started on appropriate chemotherapy with interval improvements in weight gain.
These cases illustrate the importance of cranial imaging and consideration of
diencephalic syndrome for children presenting with FTT despite normal or
increased caloric intake.
PMID- 28687693
TI - Adrenal crisis in metastatic breast cancer.
AB - A female patient with oestrogen receptor-positive and human epidermal growth
factor receptor 2 (HER2)-positive invasive lobular breast cancer presented with
progressive disease on CT scan. Some days after initiation of antineoplastic
chemotherapy and anti-HER2 targeted antibody therapy, the patient presented with
profuse diarrhoea, neutropaenia, nausea and weakness. Although Clostridium
difficile was rapidly tackled as a causative agent of gastrointestinal
complaints, clinical situation did not markedly improve despite proper
antimicrobial treatment. The patient reported profound lack of energy, while
nausea, vomiting and loose stools still persisted. Additionally slightly
exaggerated pigmentation of nonsunexposed skin and mucosal areas led us to the
assumption of proopiomelanocortin-derived peptide hypersecretion. The combination
of highly elevated adrenocorticotropic hormone and low basal cortisol levels
taken from a morning blood sample established the diagnosis of adrenal
insufficiency due to metastatic burden, leading to a near Addison crisis by
gastrointestinal complications of chemo-immune therapy. Administration of
hydrocortisone immediately relieved general symptoms .
PMID- 28687694
TI - Intraparenchymal pericatheter cyst in ventriculoperitoneal shunt failure.
PMID- 28687695
TI - Hiding in plain sight: a case of chronic disseminated histoplasmosis with central
nervous system involvement.
AB - A 64-year-old man presented with gradual onset of confusion, ataxia and 25-pound
weight loss over 3 months. MRI of the brain revealed two enhancing cerebellar
lesions suspicious for metastases. Positron emission tomography-CT showed
enhancement of cervical and axillary lymph nodes. Left axillary lymph node biopsy
showed no evidence of malignancy but instead showed fungal organisms
morphologically consistent with Histoplasma spp. Disseminated histoplasmosis with
central nervous system involvement was suspected. Further history revealed that
the patient had been having subjective fever for the past several months. He has
had mild pancytopenia for about 2 years, which had not been further evaluated.
Additionally, he had an oesophagogastroduodenoscopy 3 months prior to admission,
which had shown granulomatous gastritis. Subsequently, the diagnosis of
disseminated histoplasmosis was confirmed by serological testing and bone marrow
biopsy. The patient was started on liposomal amphotericin B. Unfortunately, the
patient had a catastrophic stroke and was transitioned to comfort care measures.
PMID- 28687696
TI - Skin eruption and long-lasting fever in a young man.
PMID- 28687697
TI - 'Scissor deformity' of the toes.
PMID- 28687698
TI - Cupping at the ends of ribs is not always rickets.
PMID- 28687699
TI - A rare case of malposition of central venous catheter detected by ultrasonography
guided saline flush test.
AB - Central venous catheter (CVC) insertion is associated with many potential
complications; malposition of the catheter is one of them. A chest X-ray is
routinely done to detect the malposition of catheter, but sometimes it has been
seen that X-ray is time-consuming and its accuracy is also low for determining
the exact position of the catheter tip. In our case, an ultrasonography (USG)
guided CVC was placed into the right internal jugular vein of the patient. As
there was no ECG change obtained during insertion of guidewire and catheter,
malposition was suspected, which was easily detected by a novel USG-guided saline
flush test. We present a case report where USG was used for detection of a
misplaced CVC (from right internal jugular vein to right subclavian vein). With
ultrasound, the location of the catheter tip can be confirmed in very less time
compared with chest X-ray.
PMID- 28687700
TI - Renal keratinising desquamative squamous metaplasia: all that hurts is not stone.
PMID- 28687701
TI - A rare case of Epstein-Barr virus mucocutaneous ulcer of the colon.
AB - Epstein-Barr virus mucocutaneous ulcer (EBVMCU) is a rare form of EBV
lymphoproliferative disorder. The disease was recently described in 2010 for the
first time in a case series and it was recently identified by the WHO
classification of haematological malignancies as a separate category among the
EBV lymphoproliferative disorders. We present a case of EBVMCU of the colon
presenting as an ulcerating inflammatory mass in a female in her mid-60s who
presented initially with abdominal pain and diarrhoea. The patient had extensive
workup for her disease and due to progression of her symptoms, she was taken for
an exploratory laparotomy. During the procedure, there was an inflammatory mass
at the caecum and severe inflammation of the caecum and the terminal ileum and
right hemicolectomy was performed. Diagnosis was confirmed by histopathology as
EBV-positive lymphoproliferative disorder best classified as EBV-positive
mucocutaneous ulcer.
PMID- 28687702
TI - Macular phlebitis in a case of dengue retinopathy.
PMID- 28687703
TI - Retraction.
PMID- 28687704
TI - Synergistic Cytotoxicity from Drugs and Cytokines In Vitro as an Approach to
Classify Drugs According to Their Potential to Cause Idiosyncratic
Hepatotoxicity: A Proof-of-Concept Study.
AB - Idiosyncratic drug-induced liver injury (IDILI) typically occurs in a small
fraction of patients and has resulted in removal of otherwise efficacious drugs
from the market. Current preclinical testing methods are ineffective in
predicting which drug candidates have IDILI liability. Recent results suggest
that immune mediators such as tumor necrosis factor-alpha (TNF) and interferon
gamma (IFN) interact with drugs that cause IDILI to kill hepatocytes. This proof
of-concept study was designed to test the hypothesis that drugs can be classified
according to their ability to cause IDILI in humans using classification modeling
with covariates derived from concentration-response relationships that describe
cytotoxic interaction with cytokines. Human hepatoma (HepG2) cells were treated
with drugs associated with IDILI or with drugs lacking IDILI liability and
cotreated with TNF and/or IFN. Detailed concentration-response relationships were
determined for calculation of parameters such as the maximal cytotoxic effect,
slope, and EC50 for use as covariates for classification modeling using logistic
regression. These parameters were incorporated into multiple classification
models to identify combinations of covariates that most accurately classified the
drugs according to their association with human IDILI. Of 14 drugs associated
with IDILI, almost all synergized with TNF to kill HepG2 cells and were
successfully classified by statistical modeling. IFN enhanced the toxicity
mediated by some IDILI-associated drugs in the presence of TNF. In contrast, of
10 drugs with little or no IDILI liability, none synergized with inflammatory
cytokines to kill HepG2 cells and were classified accordingly. The resulting
optimal model classified the drugs with extraordinary selectivity and
specificity.
PMID- 28687705
TI - Annotation and cluster analysis of spatiotemporal- and sex-related lncRNA
expression in rhesus macaque brain.
AB - Long noncoding RNAs (lncRNAs) mediate important epigenetic regulation in a wide
range of biological processes and diseases. We applied comprehensive analyses of
RNA-seq and CAGE-seq (cap analysis of gene expression and sequencing) to
characterize the dynamic changes in lncRNA expression in rhesus macaque (Macaca
mulatta) brain in four representative age groups. We identified 18 anatomically
diverse lncRNA modules and 14 mRNA modules representing spatial, age, and sex
specificities. Spatiotemporal- and sex-biased changes in lncRNA expression were
generally higher than those observed in mRNA expression. A negative correlation
between lncRNA and mRNA expression in cerebral cortex was observed and
functionally validated. Our findings offer a fresh insight into spatial-, age-,
and sex-biased changes in lncRNA expression in macaque brain and suggest that the
changes represent a previously unappreciated regulatory system that potentially
contributes to brain development and aging.
PMID- 28687706
TI - Bone Regulates Browning and Energy Metabolism Through Mature Osteoblast/Osteocyte
PPARgamma Expression.
AB - Peroxisome proliferator-activated receptor gamma (PPARgamma) is a master
regulator of energy metabolism. In bone, it is known to regulate osteoblast
differentiation and osteoclast activity. Whether PPARgamma expression in bone
cells, particularly osteocytes, regulates energy metabolism remains unknown.
Here, we show that mature osteoblast/osteocyte-specific ablation of PPARgamma in
mice (Ocy-PPARgamma-/-) alters body composition with age, namely, to produce less
fat and more lean mass, and enhances insulin sensitivity and energy expenditure
compared with wild-type mice. In addition, Ocy-PPARgamma-/- mice exhibit more
bone density, structure, and strength by uncoupling bone formation from
resorption. When challenged with a high-fat diet, Ocy-PPARgamma-/- mice retain
glycemic control, with increased browning of the adipose tissue, decreased
gluconeogenesis, and less hepatic steatosis. Moreover, these metabolic effects,
particularly an increase in fatty acid oxidation, cannot be explained by
decarboxylated osteocalcin changes, suggesting existence of other osteokines that
are under the control of PPARgamma. We further identify bone morphogenetic
protein 7 as one of them. Hence, osteocytes coregulate bone and glucose
homeostasis through a PPARgamma regulatory pathway, and its inhibition could be
clinically relevant for the prevention of glucose metabolic disorders.
PMID- 28687707
TI - Validity of Cardiovascular Data From Electronic Sources: The Multi-Ethnic Study
of Atherosclerosis and HealthLNK.
AB - BACKGROUND: Understanding the validity of data from electronic data research
networks is critical to national research initiatives and learning healthcare
systems for cardiovascular care. Our goal was to evaluate the degree of agreement
of electronic data research networks in comparison with data collected by
standardized research approaches in a cohort study. METHODS: We linked individual
level data from MESA (Multi-Ethnic Study of Atherosclerosis), a community-based
cohort, with HealthLNK, a 2006 to 2012 database of electronic health records from
6 Chicago health systems. To evaluate the correlation and agreement of blood
pressure in HealthLNK in comparison with in-person MESA examinations, and body
mass index in HealthLNK in comparison with MESA, we used Pearson correlation
coefficients and Bland-Altman plots. Using diagnoses in MESA as the criterion
standard, we calculated the performance of HealthLNK for hypertension, obesity,
and diabetes mellitus diagnosis by using International Classification of
Diseases, Ninth Revision codes and clinical data. We also identified potential
myocardial infarctions, strokes, and heart failure events in HealthLNK and
compared them with adjudicated events in MESA. RESULTS: Of the 1164 MESA
participants enrolled at the Chicago Field Center, 802 (68.9%) participants had
data in HealthLNK. The correlation was low for systolic blood pressure (0.39;
P<0.0001). In comparison with MESA, HealthLNK overestimated systolic blood
pressure by 6.5 mm Hg (95% confidence interval, 4.2-7.8). There was a high
correlation between body mass index in MESA and HealthLNK (0.94; P<0.0001).
HealthLNK underestimated body mass index by 0.3 kg/m2 (95% confidence interval,
0.4 to -0.1). With the use of International Classification of Diseases, Ninth
Revision codes and clinical data, the sensitivity and specificity of HealthLNK
queries for hypertension were 82.4% and 59.4%, for obesity were 73.0% and 89.8%,
and for diabetes mellitus were 79.8% and 93.3%. In comparison with adjudicated
cardiovascular events in MESA, the concordance rates for myocardial infarction,
stroke, and heart failure were, respectively, 41.7% (5/12), 61.5% (8/13), and
62.5% (10/16). CONCLUSIONS: These findings illustrate the limitations and
strengths of electronic data repositories in comparison with information
collected by traditional standardized epidemiological approaches for the
ascertainment of cardiovascular risk factors and events.
PMID- 28687709
TI - The Effects of Public Access Defibrillation on Survival After Out-of-Hospital
Cardiac Arrest: A Systematic Review of Observational Studies.
AB - BACKGROUND: Despite recent advances, the average survival after out-of-hospital
cardiac arrest (OHCA) remains <10%. Early defibrillation by an automated external
defibrillator is the most important intervention for patients with OHCA, showing
survival proportions >50%. Accordingly, placement of automated external
defibrillators in the community as part of a public access defibrillation program
(PAD) is recommended by international guidelines. However, different strategies
have been proposed on how exactly to increase and make use of publicly available
automated external defibrillators. This systematic review aimed to evaluate the
effect of PAD and the different PAD strategies on survival after OHCA. METHODS:
PubMed, Embase, and the Cochrane Library were systematically searched on August
31, 2015 for observational studies reporting survival to hospital discharge in
OHCA patients where an automated external defibrillator had been used by
nonemergency medical services. PAD was divided into 3 groups according to who
applied the defibrillator: nondispatched lay first responders, professional first
responders (firefighters/police) dispatched by the Emergency Medical Dispatch
Center (EMDC), or lay first responders dispatched by the EMDC. RESULTS: A total
of 41 studies were included; 18 reported PAD by nondispatched lay first
responders, 20 reported PAD by EMDC-dispatched professional first responders
(firefighters/police), and 3 reported both. We identified no qualified studies
reporting survival after PAD by EMDC-dispatched lay first responders. The overall
survival to hospital discharge after OHCA treated with PAD showed a median
survival of 40.0% (range, 9.1-83.3). Defibrillation by nondispatched lay first
responders was associated with the highest survival with a median survival of
53.0% (range, 26.0-72.0), whereas defibrillation by EMDC-dispatched professional
first responders (firefighters/police) was associated with a median survival of
28.6% (range, 9.0-76.0). A meta-analysis of the different survival outcomes could
not be performed because of the large heterogeneity of the included studies.
CONCLUSIONS: This systematic review showed a median overall survival of 40% for
patients with OHCA treated by PAD. Defibrillation by nondispatched lay first
responders was found to correlate with the highest impact on survival in
comparison with EMDC-dispatched professional first responders. PAD by EMDC
dispatched lay first responders could be a promising strategy, but evidence is
lacking.
PMID- 28687708
TI - Germline Loss-of-Function Mutations in EPHB4 Cause a Second Form of Capillary
Malformation-Arteriovenous Malformation (CM-AVM2) Deregulating RAS-MAPK
Signaling.
AB - BACKGROUND: Most arteriovenous malformations (AVMs) are localized and occur
sporadically. However, they also can be multifocal in autosomal-dominant
disorders, such as hereditary hemorrhagic telangiectasia and capillary
malformation (CM)-AVM. Previously, we identified RASA1 mutations in 50% of
patients with CM-AVM. Herein we studied non-RASA1 patients to further elucidate
the pathogenicity of CMs and AVMs. METHODS: We conducted a genome-wide linkage
study on a CM-AVM family. Whole-exome sequencing was also performed on 9
unrelated CM-AVM families. We identified a candidate gene and screened it in a
large series of patients. The influence of several missense variants on protein
function was also studied in vitro. RESULTS: We found evidence for linkage in 2
loci. Whole-exome sequencing data unraveled 4 distinct damaging variants in EPHB4
in 5 families that cosegregated with CM-AVM. Overall, screening of EPHB4 detected
47 distinct mutations in 54 index patients: 27 led to a premature stop codon or
splice-site alteration, suggesting loss of function. The other 20 are
nonsynonymous variants that result in amino acid substitutions. In vitro
expression of several mutations confirmed loss of function of EPHB4. The clinical
features included multifocal CMs, telangiectasias, and AVMs. CONCLUSIONS: We
found EPHB4 mutations in patients with multifocal CMs associated with AVMs. The
phenotype, CM-AVM2, mimics RASA1-related CM-AVM1 and also hereditary hemorrhagic
telangiectasia. RASA1-encoded p120RASGAP is a direct effector of EPHB4. Our data
highlight the pathogenetic importance of this interaction and indicts EPHB4-RAS
ERK signaling pathway as a major cause for AVMs.
PMID- 28687710
TI - Evaluating the Impact and Cost-Effectiveness of Statin Use Guidelines for Primary
Prevention of Coronary Heart Disease and Stroke.
AB - BACKGROUND: Statins are effective in the primary prevention of atherosclerotic
cardiovascular disease. The 2013 American College of Cardiology/American Heart
Association (ACC/AHA) guideline expands recommended statin use, but its cost
effectiveness has not been compared with other guidelines. METHODS: We used the
Cardiovascular Disease Policy Model to estimate the cost-effectiveness of the
ACC/AHA guideline relative to current use, Adult Treatment Panel III guidelines,
and universal statin use in all men 45 to 74 years of age and women 55 to 74
years of age over a 10-year horizon from 2016 to 2025. Sensitivity analyses
varied costs, risks, and benefits. Main outcomes were incremental cost
effectiveness ratios and numbers needed to treat for 10 years per quality
adjusted life-year gained. RESULTS: Each approach produces substantial benefits
and net cost savings relative to the status quo. Full adherence to the Adult
Treatment Panel III guideline would result in 8.8 million more statin users than
the status quo, at a number needed to treat for 10 years per quality-adjusted
life-year gained of 35. The ACC/AHA guideline would potentially result in up to
12.3 million more statin users than the Adult Treatment Panel III guideline, with
a marginal number needed to treat for 10 years per quality-adjusted life-year
gained of 68. Moderate-intensity statin use in all men 45 to 74 years of age and
women 55 to 74 years of age would result in 28.9 million more statin users than
the ACC/AHA guideline, with a marginal number needed to treat for 10 years per
quality-adjusted life-year gained of 108. In all cases, benefits would be greater
in men than women. Results vary moderately with different risk thresholds for
instituting statins and statin toxicity estimates but depend greatly on the
disutility caused by daily medication use (pill burden). CONCLUSIONS: At a
population level, the ACC/AHA guideline for expanded statin use for primary
prevention is projected to treat more people, to save more lives, and to cost
less compared with Adult Treatment Panel III in both men and women. Whether
individuals benefit from long-term statin use for primary prevention depends more
on the disutility associated with pill burden than their degree of cardiovascular
risk.
PMID- 28687711
TI - The Optimal Timing of Stage 2 Palliation for Hypoplastic Left Heart Syndrome: An
Analysis of the Pediatric Heart Network Single Ventricle Reconstruction Trial
Public Data Set.
AB - BACKGROUND: In infants requiring 3-stage single-ventricle palliation for
hypoplastic left heart syndrome, attrition after the Norwood procedure remains
significant. The effect of the timing of stage 2 palliation (S2P), a physician
modifiable factor, on long-term survival is not well understood. We hypothesized
that an optimal interval between the Norwood and S2P that both minimizes pre-S2P
attrition and maximizes post-S2P survival exists and is associated with
individual patient characteristics. METHODS: The National Institutes of
Health/National Heart, Lung, and Blood Institute Pediatric Heart Network Single
Ventricle Reconstruction Trial public data set was used. Transplant-free survival
(TFS) was modeled from (1) Norwood to S2P and (2) S2P to 3 years by using
parametric hazard analysis. Factors associated with death or heart
transplantation were determined for each interval. To account for staged
procedures, risk-adjusted, 3-year, post-Norwood TFS (the probability of TFS at 3
years given survival to S2P) was calculated using parametric conditional survival
analysis. TFS from the Norwood to S2P was first predicted. TFS after S2P to 3
years was then predicted and adjusted for attrition before S2P by multiplying by
the estimate of TFS to S2P. The optimal timing of S2P was determined by
generating nomograms of risk-adjusted, 3-year, post-Norwood, TFS versus the
interval from the Norwood to S2P. RESULTS: Of 547 included patients, 399 survived
to S2P (73%). Of the survivors to S2P, 349 (87%) survived to 3-year follow-up.
The median interval from the Norwood to S2P was 5.1 (interquartile range, 4.1
6.0) months. The risk-adjusted, 3-year, TFS was 68+/-7%. A Norwood-S2P interval
of 3 to 6 months was associated with greatest 3-year TFS overall and in patients
with few risk factors. In patients with multiple risk factors, TFS was severely
compromised, regardless of the timing of S2P and most severely when S2P was
performed early. No difference in the optimal timing of S2P existed when
stratified by shunt type. CONCLUSIONS: In infants with few risk factors,
progressing to S2P at 3 to 6 months after the Norwood procedure was associated
with maximal TFS. Early S2P did not rescue patients with greater risk factor
burdens. Instead, referral for heart transplantation may offer their best chance
at long-term survival. CLINICAL TRIAL REGISTRATION: URL:
https://www.clinicaltrials.gov. Unique identifier: NCT00115934.
PMID- 28687712
TI - Dynamic Edematous Response of the Human Heart to Myocardial Infarction:
Implications for Assessing Myocardial Area at Risk and Salvage.
AB - BACKGROUND: Clinical protocols aimed to characterize the post-myocardial
infarction (MI) heart by cardiac magnetic resonance (CMR) need to be standardized
to take account of dynamic biological phenomena evolving early after the index
ischemic event. Here, we evaluated the time course of edema reaction in patients
with ST-segment-elevation MI by CMR and assessed its implications for myocardium
at-risk (MaR) quantification both in patients and in a large-animal model.
METHODS: A total of 16 patients with anterior ST-segment-elevation MI
successfully treated by primary angioplasty and 16 matched controls were
prospectively recruited. In total, 94 clinical CMR examinations were performed:
patients with ST-segment-elevation MI were serially scanned (within the first 3
hours after reperfusion and at 1, 4, 7, and 40 days), and controls were scanned
only once. T2 relaxation time in the myocardium (T2 mapping) and the extent of
edema on T2-weighted short-tau triple inversion-recovery (ie, CMR-MaR) were
evaluated at all time points. In the experimental study, 20 pigs underwent 40
minute ischemia/reperfusion followed by serial CMR examinations at 120 minutes
and 1, 4, and 7 days after reperfusion. Reference MaR was assessed by contrast
multidetector computed tomography during the index coronary occlusion.
Generalized linear mixed models were used to take account of repeated
measurements. RESULTS: In humans, T2 relaxation time in the ischemic myocardium
declines significantly from early after reperfusion to 24 hours, and then
increases up to day 4, reaching a plateau from which it decreases from day 7.
Consequently, edema extent measured by T2-weighted short-tau triple inversion
recovery (CMR-MaR) varied with the timing of the CMR examination. These findings
were confirmed in the experimental model by showing that only CMR-MaR values for
day 4 and day 7 postreperfusion, coinciding with the deferred edema wave, were
similar to values measured by reference contrast-multidetector computed
tomography. CONCLUSIONS: Post-MI edema in patients follows a bimodal pattern that
affects CMR estimates of MaR. Dynamic changes in post-ST-segment-elevation MI
edema highlight the need for standardization of CMR timing to retrospectively
delineate MaR and quantify myocardial salvage. According to the present clinical
and experimental data, a time window between days 4 and 7 post-MI seems a good
compromise solution for standardization. Further studies are needed to study the
effect of other factors on these variables.
PMID- 28687713
TI - TLR9 is up-regulated in human and murine NASH: pivotal role in inflammatory
recruitment and cell survival.
AB - : Background and aims: TLR9 deletion protects against steatohepatitis due to
choline-amino acid depletion and high-fat diet. We measured TLR9 in human non
alcoholic steatohepatitis (NASH) livers, and tested whether TLR9 mediates
inflammatory recruitment in three murine models of non-alcoholic fatty liver
disease (NAFLD). Methods: We assayed TLR mRNA in liver biopsies from bariatric
surgery patients. Wild-type (Wt), appetite-dysregulated Alms1 mutant (foz/foz),
Tlr9-/-, and Tlr9-/-foz/foz C57BL6/J mice and bone marrow (BM) chimeras were fed
0.2% cholesterol, high-fat, high sucrose (atherogenic[Ath]) diet or chow, and
NAFLD activity score (NAS)/NASH pathology, macrophage/neutrophil infiltration,
cytokines/chemokines, and cell death markers measured in livers. Results: Hepatic
TLR9 and TLR4 mRNA were increased in human NASH but not simple steatosis, and in
Ath-fed foz/foz mice with metabolic syndrome-related NASH. Ath-fed Tlr9-/- mice
showed simple steatosis and less Th1 cytokines than Wt. Tlr9-/-foz/foz mice were
obese and diabetic, but necroinflammatory changes were less severe than
Tlr9+/+.foz/foz mice. TLR9-expressing myeloid cells were critical for Th1
cytokine production in BM chimeras. BM macrophages from Tlr9-/- mice showed M2
polarization, were resistant to M1 activation by necrotic hepatocytes/other pro
inflammatory triggers, and provoked less neutrophil chemotaxis than Wt Livers
from Ath-fed Tlr9-/- mice appeared to exhibit more markers of necroptosis
[receptor interacting protein kinase (RIP)-1, RIP-3, and mixed lineage kinase
domain-like protein (MLKL)] than Wt, and ~25% showed portal foci of mononuclear
cells unrelated to NASH pathology. CONCLUSION: Our novel clinical data and
studies in overnutrition models, including those with diabetes and metabolic
syndrome, clarify TLR9 as a pro-inflammatory trigger in NASH. This response is
mediated via M1-macrophages and neutrophil chemotaxis.
PMID- 28687714
TI - Lnc-ing inflammation to disease.
AB - Termed 'master gene regulators' long ncRNAs (lncRNAs) have emerged as the true
vanguard of the 'noncoding revolution'. Functioning at a molecular level, in most
if not all cellular processes, lncRNAs exert their effects systemically. Thus, it
is not surprising that lncRNAs have emerged as important players in human
pathophysiology. As our body's first line of defense upon infection or injury,
inflammation has been implicated in the etiology of several human diseases. At
the center of the acute inflammatory response, as well as several pathologies, is
the pleiotropic transcription factor NF-kappabeta. In this review, we attempt to
capture a summary of lncRNAs directly involved in regulating innate immunity at
various arms of the NF-kappabeta pathway that have also been validated in human
disease. We also highlight the fundamental concepts required as lncRNAs enter a
new era of diagnostic and therapeutic significance.
PMID- 28687715
TI - Resource allocation in living organisms.
AB - Quantitative prediction of resource allocation for living systems has been an
intensive area of research in the field of biology. Resource allocation was
initially investigated in higher organisms by using empirical mathematical models
based on mass distribution. A challenge is now to go a step further by
reconciling the cellular scale to the individual scale. In the present paper, we
review the foundations of modelling of resource allocation, particularly at the
cellular scale: from small macro-molecular models to genome-scale cellular
models. We enlighten how the combination of omic measurements and computational
advances together with systems biology has contributed to dramatic progresses in
the current understanding and prediction of cellular resource allocation.
Accurate genome-wide predictive methods of resource allocation based on the
resource balance analysis (RBA) framework have been developed and ensure a good
trade-off between the complexity/tractability and the prediction capability of
the model. The RBA framework shows promise for a wide range of applications in
metabolic engineering and synthetic biology, and for pursuing investigations of
the design principles of cellular and multi-cellular organisms.
PMID- 28687717
TI - Age and the fuzzy edges of embolic stroke of undetermined source: Implications
for trials.
PMID- 28687716
TI - Regulation of the trafficking and the function of the metalloprotease ADAM10 by
tetraspanins.
AB - By interacting directly with partner proteins and with one another, tetraspanins
organize a network of interactions referred to as the tetraspanin web. ADAM10 (A
Disintegrin And Metalloprotease 10), an essential membrane-anchored
metalloprotease that cleaves off the ectodomain of a large variety of cell
surface proteins including cytokines, adhesion molecules, the precursor of the
beta-amyloid peptide APP or Notch, has emerged as a major component of the
tetraspanin web. Recent studies have shown that ADAM10 associates directly with
all members (Tspan5, Tspan10, Tspan14, Tspan15, Tspan17 and Tspan33) of a
subgroup of tetraspanins having eight cysteines in the large extracellular domain
and referred to as TspanC8. All TspanC8 regulate ADAM10 exit from the endoplasmic
reticulum, but differentially regulate its subsequent trafficking and its
function, and have notably a different impact on Notch signaling. TspanC8
orthologs in invertebrates also regulate ADAM10 trafficking and Notch signaling.
It may be possible to target TspanC8 tetraspanins to modulate in a tissue- or
substrate-restricted manner ADAM10 function in pathologies such as cardiovascular
diseases, cancer or Alzheimer's disease.
PMID- 28687718
TI - Mortality trends for multiple sclerosis patients in Sweden from 1968 to 2012.
AB - OBJECTIVE: To assess trends in mortality and causes of death for patients with
multiple sclerosis (MS) relative to those without MS in Sweden. METHODS: Patients
with an MS diagnosis in Sweden between 1964 and 2012 were identified with the
Patient Register and the Multiple Sclerosis Register. For this cohort study, each
patient with MS (n = 29,617) was matched with 10 individuals without MS (n =
296,164) on sex, year of birth, vital status, and region of residence at the time
of MS diagnosis with the Total Population Register. The Causes of Death Register
was used to identify causes of death. Cox proportional hazard models were
constructed to assess whether risk of mortality was increased for patients with
MS. RESULTS: The hazard ratio (HR) for patients with MS was 2.92 (95% confidence
interval [CI] 2.86-2.99) for all-cause mortality over the entire study period.
The largest differences between the cohorts were death resulting from respiratory
(HR 5.07, 95% CI 4.87-5.26) and infectious (HR 4.07, 95% CI 3.70-4.47) diseases.
Overall and for each specific cause, there have been improvements for the MS
group and a subsequent reduction in the HR. The HR decreased from 6.52 (95% CI
5.79-7.34) for the period of 1968 to 1980 to 2.08 (95% CI 1.95-2.22) for the time
period of 2001 to 2012. An interaction between time period and MS exposure showed
that the decrease in mortality over time was statistically significant, with a
larger decrease for patients with MS than their matched comparators. CONCLUSIONS:
There has been a substantial improvement in mortality overall and for each
specified cause of death for patients with MS compared with individuals without
MS; however, large differences still remain.
PMID- 28687719
TI - Determining the optimal target blood pressure after thrombectomy: High or low?
PMID- 28687720
TI - Age- and sex-specific analysis of patients with embolic stroke of undetermined
source.
AB - OBJECTIVE: To investigate whether the correlation of age and sex with the risk of
recurrence and death seen in patients with previous ischemic stroke is also
evident in patients with embolic stroke of undetermined source (ESUS). METHODS:
We pooled datasets of 11 stroke registries from Europe and America. ESUS was
defined according to the Cryptogenic Stroke/ESUS International Working Group. We
performed Cox regression and Kaplan-Meier product limit analyses to investigate
whether age (<60, 60-80, >80 years) and sex were independently associated with
the risk for ischemic stroke/TIA recurrence or death. RESULTS: Ischemic
stroke/TIA recurrences and deaths per 100 patient-years were 2.46 and 1.01 in
patients <60 years old, 5.76 and 5.23 in patients 60 to 80 years old, 7.88 and
11.58 in those >80 years old, 3.53 and 3.48 in women, and 4.49 and 3.98 in men,
respectively. Female sex was not associated with increased risk for recurrent
ischemic stroke/TIA (hazard ratio [HR] 1.15, 95% confidence interval [CI] 0.84
1.58) or death (HR 1.35, 95% CI 0.97-1.86). Compared with the group <60 years
old, the 60- to 80- and >80-year groups had higher 10-year cumulative probability
of recurrent ischemic stroke/TIA (14.0%, 47.9%, and 37.0%, respectively, p <
0.001) and death (6.4%, 40.6%, and 100%, respectively, p < 0.001) and higher risk
for recurrent ischemic stroke/TIA (HR 1.90, 95% CI 1.21-2.98 and HR 2.71, 95% CI
1.57-4.70, respectively) and death (HR 4.43, 95% CI 2.32-8.44 and HR 8.01, 95% CI
3.98-16.10, respectively). CONCLUSIONS: Age, but not sex, is a strong predictor
of stroke recurrence and death in ESUS. The risk is ~3- and 8-fold higher in
patients >80 years compared with those <60 years of age, respectively. The age
distribution in the ongoing ESUS trials may potentially influence their power to
detect a significant treatment association.
PMID- 28687721
TI - Blood pressure levels post mechanical thrombectomy and outcomes in large vessel
occlusion strokes.
AB - OBJECTIVE: There are limited data evaluating the effect of post mechanical
thrombectomy (MT) blood pressure (BP) levels on early outcomes of patients with
large vessel occlusions (LVO). We sought to investigate the association of BP
course following MT with early outcomes in LVO. METHODS: Consecutive patients
with LVO treated with MT during a 3-year period were evaluated. Hourly systolic
BP (SBP) and diastolic BP (DBP) values were recorded for 24 hours following MT
and maximum SBP and DBP levels were identified. LVO patients with complete
reperfusion following MT were stratified in 3 groups based on post-MT achieved BP
goals: <140/90 mm Hg (intensive), <160/90 mm Hg (moderate), and <220/110 mm Hg or
<180/105 mm Hg when pretreated with IV thrombolysis (permissive hypertension).
Three-month functional independence was defined as modified Rankin Scale score of
0-2. RESULTS: A total of 217 acute ischemic stroke patients with LVO were
prospectively evaluated. A 10 mm Hg increment in maximum SBP documented during
the first 24 hours post MT was independently (p = 0.001) associated with a lower
likelihood of 3-month functional independence (odds ratio [OR] 0.70; 95%
confidence interval [CI] 0.56-0.87) and a higher odds of 3-month mortality (OR
1.49; 95% CI 1.18-1.88) after adjusting for potential confounders. In addition,
achieving a BP goal of <160/90 mm Hg during the first 24 hours following MT was
independently associated with a lower likelihood of 3-month mortality (OR 0.08;
95% CI 0.01-0.54; p = 0.010) in comparison to permissive hypertension.
CONCLUSIONS: High maximum SBP levels following MT are independently associated
with increased likelihood of 3-month mortality and functional dependence in LVO
patients. Moderate BP control is also related to lower odds of 3-month mortality
in comparison to permissive hypertension.
PMID- 28687722
TI - A meta-analysis on progressive atrophy in intractable temporal lobe epilepsy:
Time is brain?
AB - OBJECTIVE: It remains unclear whether drug-resistant temporal lobe epilepsy (TLE)
is associated with cumulative brain damage, with no expert consensus and no
quantitative syntheses of the available evidence. METHODS: We conducted a
systematic review and meta-analysis of MRI studies on progressive atrophy,
searching PubMed and Ovid MEDLINE databases for cross-sectional and longitudinal
quantitative MRI studies on drug-resistant TLE. RESULTS: We screened 2,976
records and assessed eligibility of 248 full-text articles. Forty-two articles
met the inclusion criteria for quantitative evaluation. We observed a
predominance of cross-sectional studies, use of different clinical indices of
progression, and high heterogeneity in age-control procedures. Meta-analysis of
18/1 cross-sectional/longitudinal studies on hippocampal atrophy (n = 979
patients) yielded a pooled effect size of r = -0.42 for ipsilateral atrophy
related to epilepsy duration (95% confidence interval [CI] -0.51 to -0.32; p <
0.0001; I2 = 65.22%) and r = -0.35 related to seizure frequency (95% CI -0.47 to
0.22; p < 0.0001; I2 = 61.97%). Sensitivity analyses did not change the results.
Narrative synthesis of 25/3 cross-sectional/longitudinal studies on whole brain
atrophy (n = 1,504 patients) indicated that >80% of articles reported duration
related progression in extratemporal cortical and subcortical regions. Detailed
analysis of study design features yielded low to moderate levels of evidence for
progressive atrophy across studies, mainly due to dominance of cross-sectional
over longitudinal investigations, use of diverse measures of seizure estimates,
and absence of consistent age control procedures. CONCLUSIONS: While the
neuroimaging literature is overall suggestive of progressive atrophy in drug
resistant TLE, published studies have employed rather weak designs to directly
demonstrate it. Longitudinal multicohort studies are needed to unequivocally
differentiate aging from disease progression.
PMID- 28687723
TI - Myoclonic dystonia (DYT11) responsive to insulin therapy: A case report.
PMID- 28687724
TI - The state of academic neurology departments in the United States, 2016: A
national survey.
PMID- 28687725
TI - Design and Development of a Novel Chalcone Derivative as an Anticholinesterase
Inhibitor for Possible Treatment of Dementia.
AB - BACKGROUND Cognitive decline (e.g., memory loss), which mainly occurs in the
elderly, is termed dementia. In the present study, we intended to explore the
cholinesterase inhibitory activity of some novel synthesized chalcones, together
with their effect on beta-amyloid anti-aggregation. MATERIAL AND METHODS A novel
class of chalcone derivatives have been synthesized and characterized by FT-IR,
1H-NMR, 13C-NMR, and mass and elemental analysis. These derivatives were later
used for the determination of acetylcholinesterase (AChE) inhibitory and b
amyloid anti-aggregation activity. RESULTS The results of the study showed that
among the developed compounds, 8g inhibits AChE more prominently than BuChE, as
suggested by a selectivity index (SI) of 2.88. Furthermore, the most potent
compound, 8g, showed considerable action in inhibition of beta-secretase and
Abeta aggregation, but not as prominent as that of curcumin as a standard.
CONCLUSIONS In conclusion, our study revealed a novel class of chalcone
derivatives as a selective inhibitor of AChE with considerably action against
beta-secretase and Abeta aggregation. Our results may be useful in developing AD
drug therapy and warrant further investigation to generate more advanced
analogues.
PMID- 28687726
TI - Propagation-based Phase-Contrast X-ray Imaging at a Compact Light Source.
AB - We demonstrate the applicability of propagation-based X-ray phase-contrast
imaging at a laser-assisted compact light source with known phantoms and the
lungs and airways of a mouse. The Munich Compact Light Source provides a quasi
monochromatic beam with partial spatial coherence, and high flux relative to
other non-synchrotron sources (up to 1010 ph/s). In our study we observe
significant edge-enhancement and quantitative phase-retrieval is successfully
performed on the known phantom. Furthermore the images of a small animal show the
potential for live bio-imaging research studies that capture biological function
using short exposures.
PMID- 28687727
TI - Alpha 2 Na+,K+-ATPase silencing induces loss of inflammatory response and ouabain
protection in glial cells.
AB - Ouabain (OUA) is a cardiac glycoside that binds to Na+,K+-ATPase (NKA), a
conserved membrane protein that controls cell transmembrane ionic concentrations
and requires ATP hydrolysis. At nM concentrations, OUA activates signaling
pathways that are not related to its typical inhibitory effect on the NKA pump.
Activation of these signaling pathways protects against some types of injury of
the kidneys and central nervous system. There are 4 isoforms of the alpha subunit
of NKA, which are differentially distributed across tissues and may have
different physiological roles. Glial cells are important regulators of injury and
inflammation in the brain and express the alpha1 and alpha2 NKA isoforms. This
study investigated the role of alpha2 NKA in OUA modulation of the
neuroinflammatory response induced by lipopolysaccharide (LPS) in mouse primary
glial cell cultures. LPS treatment increased lactate dehydrogenase release, while
OUA did not decrease cell viability and blocked LPS-induced NF-kappaB activation.
Silencing alpha2 NKA prevented ERK and NF-kappaB activation by LPS. alpha2 NKA
also regulates TNF-alpha and IL-1beta levels. The data reported here indicate a
significant role of alpha2 NKA in regulating central LPS effects, with
implications in the associated neuroinflammatory processes.
PMID- 28687728
TI - Acinetobacter sp. DW-1 immobilized on polyhedron hollow polypropylene balls and
analysis of transcriptome and proteome of the bacterium during phenol
biodegradation process.
AB - Phenol is a hazardous chemical known to be widely distributed in aquatic
environments. Biodegradation is an attractive option for removal of phenol from
water sources. Acinetobacter sp. DW-1 isolated from drinking water biofilters can
use phenol as a sole carbon and energy source. In this study, we found that
Immobilized Acinetobacter sp. DW-1cells were effective in biodegradation of
phenol. In addition, we performed proteome and transcriptome analysis of
Acinetobacter sp. DW-1 during phenol biodegradation. The results showed that
Acinetobacter sp. DW-1 degrades phenol mainly by the ortho pathway because of the
induction of phenol hydroxylase, catechol-1,2-dioxygenase. Furthermore, some
novel candidate proteins (OsmC-like family protein, MetA-pathway of phenol
degradation family protein, fimbrial protein and coenzyme F390 synthetase) and
transcriptional regulators (GntR/LuxR/CRP/FNR/TetR/Fis family transcriptional
regulator) were successfully identified to be potentially involved in phenol
biodegradation. In particular, MetA-pathway of phenol degradation family protein
and fimbrial protein showed a strong positive correlation with phenol
biodegradation, and Fis family transcriptional regulator is likely to exert its
effect as activators of gene expression. This study provides valuable clues for
identifying global proteins and genes involved in phenol biodegradation and
provides a fundamental platform for further studies to reveal the phenol
degradation mechanism of Acinetobacter sp.
PMID- 28687729
TI - Spectral clustering using Nystrom approximation for the accurate identification
of cancer molecular subtypes.
AB - A major challenge in clinical cancer research is the identification of accurate
molecular subtype. While unsupervised clustering methods have been applied for
class discovery, this clustering method remains a bottleneck in developing
accurate method for molecular subtype discovery. In this analysis, we hypothesize
that spectral clustering method could identify molecular subtypes in correlation
with survival outcomes. We propose an accurate subtype identification method,
Cancer Subtype Identification with Spectral Clustering using Nystrom
approximation (CSISCN), for the discovery of molecular subtypes, based on
spectral clustering method. CSISCN could be used to improve gene expression-based
identification of breast cancer molecular subtypes. We demonstrated that CSISCN
identified the molecular subtypes with distinct clinical outcomes and was valid
for the number of molecular subtypes. Furthermore, CSISCN identified molecular
subtypes for improving clinical and molecular relevance which significantly
outperformed consensus clustering and spectral clustering methods. To test the
general applicability of the CSISCN, we further applied it on human CRC datasets
and AML datasets and demonstrated superior performance as compared to consensus
clustering method. In summary, CSISCN demonstrated the great potential in gene
expression-based subtype identification.
PMID- 28687730
TI - Fluvoxamine stimulates oligodendrogenesis of cultured neural stem cells and
attenuates inflammation and demyelination in an animal model of multiple
sclerosis.
AB - Multiple Sclerosis (MS) require medications controlling severity of the pathology
and depression, affecting more than half of the patients. In this study, the
effect of antidepressant drug fluvoxamine, a selective serotonin reuptake
inhibitor, was investigated in vitro and in vivo. Nanomolar concentrations of
fluvoxamine significantly increased cell viability and proliferation of neural
stem cells (NSCs) through increasing mRNA expression of Notch1, Hes1 and Ki-67,
and protein levels of NICD. Also, physiological concentrations of fluvoxamine
were optimal for NSC differentiation toward oligodendrocytes, astrocytes and
neurons. In addition, fluvoxamine attenuated experimental autoimmune
encephalomyelitis (EAE) severity, a rat MS model, by significantly decreasing its
clinical scores. Moreover, fluvoxamine treated EAE rats showed a decrease in IFN
gamma serum levels and an increase in IL-4, pro- and anti-inflammatory cytokines
respectively, compared to untreated EAE rats. Furthermore, immune cell
infiltration and demyelination plaque significantly decreased in spinal cords of
fluvoxamine-treated rats, which was accompanied by an increase in protein
expression of MBP and GFAP positive cells and a decrease in lactate serum levels,
a new biomarker of MS progression. In summary, besides its antidepressant
activity, fluvoxamine stimulates proliferation and differentiation of NSCs
particularly toward oligodendrocytes, a producer of CNS myelin.
PMID- 28687731
TI - 3D free-standing nitrogen-doped reduced graphene oxide aerogel as anode material
for sodium ion batteries with enhanced sodium storage.
AB - Sodium ion batteries have drawn extensive attentions for large-scale energy
storage to replace lithium ion batteries primarily due to the natural abundance
of sodium resource and low cost, but their energy density and electrochemical
performance are hindered by the sluggish diffusion kinetics of sodium ion.
Herein, free-standing nitrogen-doped graphene aerogel has been fabricated via
hydrothermal reaction as the potential anode material for sodium ion batteries.
The three dimensional porous network structure of the graphene aerogel provides
sufficient interstitial space for sodium ion accommodation, allowing fast and
reversible ion intercalation/de-intercalation. The nitrogen doping could
introduce defects on the graphene sheets, making the feasible transport of large
sized sodium ion. Benefiting from the effective structure and nitrogen doping,
the obtained material demonstrates high reversible capacities, good cycling
performance (287.9 mA h g-1 after 200 cycles at a current density of 100 mA g-1),
especially superior rate capability (151.9 mA h g-1 at a high current density of
5 A g-1).
PMID- 28687732
TI - The Cannabinoid Receptor Interacting Proteins 1 of zebrafish are not required for
morphological development, viability or fertility.
AB - The Cannabinoid Receptor Interacting Protein 1 (Cnrip1) was discovered as an
interactor with the intracellular region of Cannabinoid Receptor 1 (CB1R, also
known as Cnr1 or CB1). Functional assays in mouse show cannabinoid sensitivity
changes and Cnrip1 has recently been suggested to control eye development in
Xenopus laevis. Two Cnrip1 genes are described in zebrafish, cnrip1a and cnrip1b.
In situ mRNA hybridisation revealed accumulation of mRNA encoding each gene
primarily in brain and spinal cord, but also elsewhere. For example, cnrip1b is
expressed in forming skeletal muscle. CRISPR/Cas9 genome editing generated
predicted null mutations in cnrip1a and cnrip1b. Each mutation triggered nonsense
mediated decay of the respective mRNA transcript. No morphological or behavioural
phenotype was observed in either mutant. Moreover, fish lacking both Cnrip1a and
Cnrip1b both maternally and zygotically are viable and fertile and no phenotype
has so far been detected despite strong evolutionary conservation over at least
400 Myr.
PMID- 28687733
TI - Catechol-O-methyltransferase polymorphism is associated with the cortico
cerebellar functional connectivity of executive function in children with
attention-deficit/hyperactivity disorder.
AB - The cerebellum, although traditionally considered a motor structure, has been
increasingly recognized to play a role in regulating executive function, the
dysfunction of which is a factor in attention-deficit/hyperactivity disorder
(ADHD). Additionally, catechol-O-methyltransferase (COMT) polymorphism has been
reported to be associated with executive function. We examined whether the
cortico-cerebellar executive function network is altered in children with ADHD
and whether COMT polymorphism is associated with the altered network. Thirty-one
children with ADHD and thirty age- and IQ-matched typically developing (TD)
controls underwent resting-state functional MRI, and functional connectivity of
executive function-related Crus I/II in the cerebellum was analysed. COMT
Val158Met genotype data were also obtained from children with ADHD. Relative to
TD controls, children with ADHD showed significantly lower functional
connectivity of the right Crus I/II with the left dorsolateral prefrontal cortex.
Additionally, the functional connectivity of children with ADHD was modulated by
COMT polymorphism, with Met-carriers exhibiting significantly lower functional
connectivity than the Val/Val genotype. These results suggest the existence of
variations, such as ethnic differences, in COMT genetic effects on the cortico
cerebellar executive function network. These variations contribute to
heterogeneity in ADHD. Further neuroimaging genetics study might lead to the
development of fundamental therapies that target ADHD pathophysiology.
PMID- 28687735
TI - Effect of carrier confinement on effective mass of excitons and estimation of
ultralow disorder in Al x Ga1-x As/GaAs quantum wells by magneto
photoluminescence.
AB - Effect of charge carrier confinement and ultra-low disorder acquainted in
AlGaAs/GaAs multi-quantum well system is investigated via Magneto
photoluminescence spectroscopy. Significant increase of effective mass is
observed for the confined exciton in narrow QWs. The foremost reason behind such
an observation is due to the induced non-parabolicity in bands. Moreover, as the
thickness of the QW are reduced, confined excitons in QW experience atomic
irregularities at the hetero-junctions and their effects are prominent in the
photoluminescence linewidth. Amount of photoluminescence line-broadening caused
by the atomic irregularities at the hetero-junctions is correlated with average
fluctuation (delta 1) in QW thickness. The estimated delta 1 for
Al0.3Ga0.7As/GaAs QWs are found to be +/-(0.14 - 1.6)* 'one monolayer thickness
of GaAs layer'. Further, the strong perturbations due to magnetic field in a
system helps in realizing optical properties of exciton in QWs, where magnetic
field is used as a probe to detect ultralow defects in the QW. Additionally, the
influence of magnetic field on the free and bound exciton luminescence is
explained by a simple model. The proposed approach for measuring the interface
and volume defects in an ultra-low disordered system by Magneto-PL spectroscopy
technique will be highly beneficial in high mobility devices for advanced
applications.
PMID- 28687734
TI - HpaB-Dependent Secretion of Type III Effectors in the Plant Pathogens Ralstonia
solanacearum and Xanthomonas campestris pv. vesicatoria.
AB - Plant pathogenic bacteria exerts their pathogenicity through the injection of
large repertoires of type III effectors (T3Es) into plant cells, a mechanism
controlled in part by type III chaperones (T3Cs). In Ralstonia solanacearum, the
causal agent of bacterial wilt, little is known about the control of type III
secretion at the post-translational level. Here, we provide evidence that the
HpaB and HpaD proteins do act as bona fide R. solanacearum class IB chaperones
that associate with several T3Es. Both proteins can dimerize but do not interact
with each other. After screening 38 T3Es for direct interactions, we highlighted
specific and common interacting partners, thus revealing the first picture of the
R. solanacearum T3C-T3E network. We demonstrated that the function of HpaB is
conserved in two phytopathogenic bacteria, R. solanacearum and Xanthomonas
campestris pv. vesicatoria (Xcv). HpaB from Xcv is able to functionally
complement a R. solanacearum hpaB mutant for hypersensitive response elicitation
on tobacco plants. Likewise, Xcv is able to translocate a heterologous T3E from
R. solanacearum in an HpaB-dependent manner. This study underlines the central
role of the HpaB class IB chaperone family and its potential contribution to the
bacterial plasticity to acquire and deliver new virulence factors.
PMID- 28687737
TI - The chloride/phosphate ratio combined with alkaline phosphatase as a valuable
predictive marker for primary hyperparathyroidism in Chinese individuals.
AB - The chloride/phosphate ratio (Cl/PO4) has been suggested to have a role in
primary hyperparathyroidism (PHPT), but the associations between Cl/PO4 combined
with ALP level and PHPT has not been well-studied. Our aim was to investigate the
predictive value of combination Cl/PO4 with ALP for PHPT. A cross-sectional
retrospective analysis was conducted to examine 172 patients diagnosed with PHPT
categorized into two groups: normocalcaemic primary hyperparathyroidism (NPHPT)
group and hypercalcaemia PHPT group. We found that Cl/PO4 levels and ALP levels
in the NPHPT and hypercalcaemia PHPT group were both significantly higher than
normal controls. Cl/PO4 and ALP levels were an independent risk factor for PHPT.
Cl/PO4 combined with ALP increased the receiver-operating characteristic curves
(ROC-AUC) and the diagnostic value in NPHPT and hypercalcaemia PHPT group (0.913;
95% CI, 0.744-1.000 and 0.932; 95% CI, 0.897-0.966, respectively), specificity of
92.8% and sensitivity of 98%. In conclusion, combination Cl/PO4 with ALP might be
a low-cost, simple, available predictive marker of PHPT in Chinese individuals,
particularly Chinese remote region where the method used to measure PTH cannot be
done. Moreover, due to serum calcium level in NPHPT, Cl/PO4 combined with ALP
level measurement have great potential to predict significant occurrence of
NPHPT.
PMID- 28687736
TI - Association between BRAF V600E Mutation and Ultrasound Features in Papillary
Thyroid Carcinoma Patients with and without Hashimoto's Thyroiditis.
AB - To assess the association between BRAF V600E mutation and ultrasound (US)
features in papillary thyroid carcinoma (PTC) patients with and without
Hashimoto's thyroiditis (HT). We retrospectively reviewed the US features and
status of BRAF V600E mutation in 438 consecutive patients with surgically
confirmed PTCs. The association between BRAF mutation and US features were
analyzed. In addition, we conducted subgroup analyses in terms of coexistent HT.
The BRAF mutation was found in 86.5% of patients (379 of 438). Patient age (OR:
1.028, P = 0.010), age >= 50 y (OR: 1.904, P = 0.030), and microcalcification
(OR: 2.262, P = 0.015) on US were significantly associated with BRAF mutation in
PTC patients. Solid component (OR: 5.739, P = 0.019) on US was the significant
predictor for BRAF mutation in patients with HT, while age (OR: 1.036, P = 0.017)
and microcalcification (OR: 3.093, P = 0.017) were significantly associated with
BRAF mutation in patients without HT. In conclusion, older age and
microcalcification are risk factors for BRAF mutation in PTC patients, especially
in those without HT. For those with HT, however, PTCs with BRAF mutation tend to
be solid on ultrasound. These factors might be considered when making treatment
planning or prognosis evaluation.
PMID- 28687739
TI - On Local Unitary Equivalence of Two and Three-qubit States.
AB - We study the local unitary equivalence for two and three-qubit mixed states by
investigating the invariants under local unitary transformations. For two-qubit
system, we prove that the determination of the local unitary equivalence of 2
qubits states only needs 14 or less invariants for arbitrary two-qubit states.
Using the same method, we construct invariants for three-qubit mixed states. We
prove that these invariants are sufficient to guarantee the LU equivalence of
certain kind of three-qubit states. Also, we make a comparison with earlier
works.
PMID- 28687738
TI - A possible origin population of pathogenic intestinal nematodes, Strongyloides
stercoralis, unveiled by molecular phylogeny.
AB - Humans and dogs are the two major hosts of Strongyloides stercoralis, an
intestinal parasitic nematode. To better understand the phylogenetic
relationships among S. stercoralis isolates infecting humans and dogs and to
assess the zoonotic potential of this parasite, we analyzed mitochondrial Cox1,
nuclear 18S rDNA, 28S rDNA, and a major sperm protein domain-containing protein
genes. Overall, our analyses indicated the presence of two distinct lineages of
S. stercoralis (referred to as type A and type B). While type A parasites were
isolated both from humans and dogs in different countries, type B parasites were
found exclusively in dogs, indicating that the type B has not adapted to infect
humans. These epidemiological data, together with the close phylogenetic
relationship of S. stercoralis with S. procyonis, a Strongyloides parasite of
raccoons, possibly indicates that S. stercoralis originally evolved as a canid
parasite, and later spread into humans. The inability to infect humans might be
an ancestral character of this species and the type B might be surmised to be an
origin population from which human-infecting strains are derived.
PMID- 28687741
TI - InSAR constraints on soil moisture evolution after the March 2015 extreme
precipitation event in Chile.
AB - ABSTARCT: Constraints on soil moisture can guide agricultural practices, act as
input into weather, flooding and climate models and inform water resource
policies. Space-based interferometric synthetic aperture radar (InSAR)
observations provide near-global coverage, even in the presence of clouds, of
proxies for soil moisture derived from the amplitude and phase content of radar
imagery. We describe results from a 1.5 year-long InSAR time series spanning the
March, 2015 extreme precipitation event in the hyperarid Atacama desert of Chile,
constraining the immediate increase in soil moisture and drying out over the
following months, as well as the response to a later, smaller precipitation
event. The inferred temporal evolution of soil moisture is remarkably consistent
between independent, overlapping SAR tracks covering a region ~100 km in extent.
The unusually large rain event, combined with the extensive spatial and temporal
coverage of the SAR dataset, present an unprecedented opportunity to image the
time-evolution of soil characteristics over different surface types. Constraints
on the timescale of shallow water storage after precipitation events are
increasingly valuable as global water resources continue to be stretched to their
limits and communities continue to develop in flood-prone areas.
PMID- 28687740
TI - Organization and hierarchy of the human functional brain network lead to a chain
like core.
AB - The brain is a paradigmatic example of a complex system: its functionality
emerges as a global property of local mesoscopic and microscopic interactions.
Complex network theory allows to elicit the functional architecture of the brain
in terms of links (correlations) between nodes (grey matter regions) and to
extract information out of the noise. Here we present the analysis of functional
magnetic resonance imaging data from forty healthy humans at rest for the
investigation of the basal scaffold of the functional brain network organization.
We show how brain regions tend to coordinate by forming a highly hierarchical
chain-like structure of homogeneously clustered anatomical areas. A maximum
spanning tree approach revealed the centrality of the occipital cortex and the
peculiar aggregation of cerebellar regions to form a closed core. We also report
the hierarchy of network segregation and the level of clusters integration as a
function of the connectivity strength between brain regions.
PMID- 28687742
TI - Zn(II) mediates vancomycin polymerization and potentiates its antibiotic activity
against resistant bacteria.
AB - Vancomycin is known to bind to Zn(II) and can induce a zinc starvation response
in bacteria. Here we identify a novel polymerization of vancomycin dimers by
structural analysis of vancomycin-Zn(II) crystals and fibre X-ray diffraction.
Bioassays indicate that this structure is associated with an increased antibiotic
activity against bacterial strains possessing high level vancomycin resistance
mediated by the reprogramming of peptidoglycan biosynthesis to use precursors
terminating in D-Ala-D-Lac in place of D-Ala-D-Ala. Polymerization occurs via
interaction of Zn(II) with the N-terminal methylleucine group of vancomycin, and
we show that the activity of other glycopeptide antibiotics with this feature can
also be similarly augmented by Zn(II). Construction and analysis of a model
strain predominantly using D-Ala-D-Lac precursors for peptidoglycan biosynthesis
during normal growth supports the hypothesis that Zn(II) mediated vancomycin
polymerization enhances the binding affinity towards these precursors.
PMID- 28687743
TI - Partial Melting of Subducted Sediments Produced Early Mesozoic Calc-alkaline
Lamprophyres from Northern Guangxi Province, South China.
AB - There is growing agreement that subducted sediments recycled into the deep mantle
could make a significant contribution to the generation of various mantle-derived
rocks. However, solid evidence and examples to support this view are few, and
whether or not the subducted sediments can act as the dominating material source
for the magma is unclear. Here, we report a comprehensive geochemical study that
demonstrates that the newly identified Early Mesozoic calc-alkaline lamprophyres
in the northern Guangxi Province, southeastern Yangtze Block in South China were
likely derived in large part from the partial melting of the subducted
terrigenous sediments in the deep mantle. The investigated lamprophyres are SiO2
rich minettes, characterized by moderate TFeO and MgO and high Mg# (>70). The
multi-element pattern shows a typical crustal-like signature, such as enrichments
in large-ion lithophile elements (LILE) and light rare earth elements (LREE) with
troughs in Nb-Ta, Ti and Eu and peaks in Th-U and Pb. These rocks also show
sediment-like ratios of Nb/U, Nb/Th and Ce/Pb, together with extremely radiogenic
87Sr/86Sr (0.71499-0.71919), unradiogenic 143Nd/144Nd (0.51188-0.51195) and
radiogenic 207Pb/204Pb (15.701-15.718) isotopic compositions.
PMID- 28687744
TI - CCM111, the water extract of Antrodia cinnamomea, regulates immune-related
activity through STAT3 and NF-kappaB pathways.
AB - Antrodia cinnamomea (AC) exhibits many bioactivities, including anti
inflammatory, anti-cancer, and hepatoprotection activities. Many researchers have
studied the functions of the components or fractions of AC, but the functions of
the original extractions of AC have not been studied. In addition, the detailed
relationship between AC and immune-related signaling pathways is unclear. In this
study, we screened the effects of CCM111, which is the extract of AC, on seven
immune-related signaling pathways and further investigated whether CCM111 can
influence inflammation. Interestingly, our results showed that CCM111
significantly inhibited the IL-6-stimulated STAT3 pathway and the LPS-stimulated
NF-kappaB pathway in macrophages. CCM111 also decreased the phosphorylation of
STAT3, Tyk2 and the nuclear translocation of p65. Moreover, CCM111 and F4, a
fraction of CCM111, down-regulated nitric oxide (NO) production, the protein
levels of iNOS and COX-2, and inflammatory cytokines in macrophage cells.
Therefore, our study suggested that CCM111 has the potential to be developed as
an effective anti-inflammatory agent.
PMID- 28687745
TI - Biochemical and genetic predictors of overall survival in patients with
metastatic pancreatic cancer treated with capecitabine and nab-paclitaxel.
AB - Pancreatic cancer is a dismal disease with a mortality rate almost similar to its
incidence rate. To date, there are neither validated predictive nor prognostic
biomarkers for this lethal disease. Thus, the aim of the present study was to
retrospectively investigate the capability of biochemical parameters and
molecular profiles to predict survival of patients with metastatic pancreatic
ductal adenocarcinoma (mPDAC) who participated in a phase II clinical trial to
test the safety and efficacy of the combination treatment of capecitabine plus
nab-paclitaxel. Herein, we investigated the association of 18 biochemical
parameters obtained from routine diagnosis and the clinical outcome of the 30
patients enrolled in the clinical trial. Furthermore, we analysed formalin-fixed
paraffin-embedded (FFPE) tumour tissue to identify molecular biomarkers via RNA
seq and the Illumina TruSeq Amplicon Cancer panel which covers 48 hotspot genes.
Our analysis identified SERPINB7 as a novel transcript and a DNA mutation
signature that might predict a poor outcome of disease. Moreover, we identified
the bilirubin basal level as an independent predictive factor for overall
survival in our study cohort.
PMID- 28687746
TI - On the improved electrochemistry of hybrid conducting-redox polymer electrodes.
AB - The electrochemistry of poly(2,5-dihydroxyaniline) (PDHA), a novel hybrid
molecular configuration with redox active sites and electrical charge conduction
along the polymer chain, has been recently reported. The theoretical capacity of
this material is estimated at 443 mAh g-1, with high power performances being
proposed given the intrinsic electrical conductivity. However, the initial
results were below the expectations: only half the theoretical capacity attained,
poor cycling stability and modest power behavior calling for further
investigations on improving these performances. Herein we detail the optimized
chemical synthesis and electrode formulation for poly(2,5-dihydroxyaniline)
resulting in improved cycling stability, power performances and defined
electrochemical response. We also detail the alternative electrochemical
synthesis and activation route for PDHA and compare the results with the chemical
approach.
PMID- 28687748
TI - Evaluating methane inventories by isotopic analysis in the London region.
AB - A thorough understanding of methane sources is necessary to accomplish methane
reduction targets. Urban environments, where a large variety of methane sources
coexist, are one of the most complex areas to investigate. Methane sources are
characterised by specific delta13C-CH4 signatures, so high precision stable
isotope analysis of atmospheric methane can be used to give a better
understanding of urban sources and their partition in a source mix. Diurnal
measurements of methane and carbon dioxide mole fraction, and isotopic values at
King's College London, enabled assessment of the isotopic signal of the source
mix in central London. Surveys with a mobile measurement system in the London
region were also carried out for detection of methane plumes at near ground
level, in order to evaluate the spatial allocation of sources suggested by the
inventories. The measured isotopic signal in central London (-45.7 +/-0.50/00)
was more than 20/00 higher than the isotopic value calculated using emission
inventories and updated delta13C-CH4 signatures. Besides, during the mobile
surveys, many gas leaks were identified that are not included in the inventories.
This suggests that a revision of the source distribution given by the emission
inventories is needed.
PMID- 28687747
TI - Lamin B1 levels modulate differentiation into neurons during embryonic
corticogenesis.
AB - Lamin B1, a key component of the nuclear lamina, plays an important role in brain
development. Ablation of endogenous Lamin B1 (Lmnb1) in the mouse strongly
impairs embryonic brain development and corticogenesis. However, the mechanisms
underlying these neurodevelopmental effects are unknown. Here, we report that
Lamin B1 levels modulate the differentiation of murine neural stem cells (NSCs)
into neurons and astroglial-like cells. In vitro, endogenous Lmnb1 depletion
favors NSC differentiation into glial fibrillar acidic protein (GFAP)
immunoreactive cells over neurons, while overexpression of human Lamin B1 (LMNB1)
increases the proportion of neurons. In Lmnb1-null embryos, neurogenesis is
reduced, while in vivo Lmnb1 silencing in mouse embryonic brain by in utero
electroporation of a specific Lmnb1 sh-RNA results in aberrant cortical
positioning of neurons and increased expression of the astrocytic marker GFAP in
the cortex of 7-day old pups. Together, these results indicate that finely tuned
levels of Lamin B1 are required for NSC differentiation into neurons, proper
expression of the astrocytic marker GFAP and corticogenesis.
PMID- 28687749
TI - Inhibition of highly pathogenic avian influenza (HPAI) virus by a peptide derived
from vFLIP through its direct destabilization of viruses.
AB - The antiviral activities of synthesized Kalpha2-helix peptide, which was derived
from the viral FLICE-like inhibitor protein (vFLIP) of Kaposi's sarcoma
associated herpesvirus (KSHV), against influenza A virus (IAV) were investigated
in vitro and in vivo, and mechanisms of action were suggested. In addition to the
robust autophagy activity of the Kalpha2-helix peptide, the present study showed
that treatment with the Kalpha2 peptide fused with the TAT peptide significantly
inhibited IAV replication and transmission. Moreover, TAT-Kalpha2 peptide
protected the mice, that were challenged with lethal doses of highly pathogenic
influenza A H5N1 or H1N1 viruses. Mechanistically, we found that TAT-Kalpha2
peptide destabilized the viral membranes, depending on their lipid composition of
the viral envelop. In addition to IAV, the Kalpha2 peptide inhibited infections
with enveloped viruses, such as Vesicular Stomatitis Virus (VSV) and Respiratory
Syncytial Virus (RSV), without cytotoxicity. These results suggest that TAT
Kalpha2 peptide is a potential antiviral agent for controlling emerging or re
emerging enveloped viruses, particularly diverse subtypes of IAVs.
PMID- 28687750
TI - 5T4-specific chimeric antigen receptor modification promotes the immune efficacy
of cytokine-induced killer cells against nasopharyngeal carcinoma stem cell-like
cells.
AB - Relapse and metastasis of nasopharyngeal carcinoma (NPC) are presumably
attributed to cancer stem cells (CSCs). In recent years, chimeric antigen
receptor (CAR)-modified immune effector cells have been shown to have impressive
antitumour efficacy. In this study, we aimed to identify appropriate tumour
associated antigens predominantly expressed on NPC stem cells (NPCSCs) and
determine their suitability for CAR-engineered cytokine-induced killer (CIK) cell
therapy against NPC. By investigating the expression patterns of potential target
antigens (ROR1, 5T4 and CAIX) in NPC, we found that the oncofetal antigen 5T4 was
predominately expressed in NPC cell lines and tissues but absent in non-cancerous
nasopharyngeal tissues. Moreover, significantly enhanced expression of 5T4 in NPC
spheroids revealed its relationship with putative NPCSCs. Hence, we designed a
CAR construct (5T4-28Z) specific for 5T4 and generated CAR-transduced CIK cells.
Our results showed that the artificial CAR was efficiently expressed on the
surface of CIK cells and that no native phenotypes were altered by the gene
transduction. Functional assays revealed that 5T4-28Z-CIK cells possessed both
CAR-mediated and CAR-independent anti-NPC activity and were capable of
efficiently attacking NPC cells, especially NPCSC-like cells in vitro, suggesting
that they might serve as an attractive tool for developing efficient therapies
against NPC.
PMID- 28687751
TI - The interaction of the bioinsecticide PA1b (Pea Albumin 1 subunit b) with the
insect V-ATPase triggers apoptosis.
AB - PA1b (Pea Albumin 1, subunit b) peptide is an entomotoxin, extracted from Legume
seeds, with a lethal activity towards several insect pests, such as mosquitoes,
some aphids and cereal weevils. This toxin acts by binding to the subunits c and
e of the plasma membrane H+-ATPase (V-ATPase) in the insect midgut. In this
study, two cereal weevils, the sensitive Sitophilus oryzae strain WAA42, the
resistance Sitophilus oryzae strain ISOR3 and the insensitive red flour beetle
Tribolium castaneum, were used in biochemical and histological experiments to
demonstrate that a PA1b/V-ATPase interaction triggers the apoptosis mechanism,
resulting in insect death. Upon intoxication with PA1b, apoptotic bodies are
formed in the cells of the insect midgut. In addition, caspase-3 enzyme activity
occurs in the midgut of sensitive weevils after intoxication with active PA1b,
but not in the midgut of resistant weevils. These biochemical data were confirmed
by immuno-histochemical detection of the caspase-3 active form in the midgut of
sensitive weevils. Immuno-labelling experiments also revealed that the caspase-3
active form and V-ATPase are close-localized in the insect midgut. The results
concerning this unique peptidic V-ATPase inhibitor pave the way for the
utilization of PA1b as a promising, more selective and eco-friendly insecticide.
PMID- 28687752
TI - Heliosterpenoids A and B, two Novel Jatrophane-Derived Diterpenoids with a
5/6/4/6 Ring System from Euphorbia helioscopia.
AB - Heliosterpenoids A and B (1 and 2), two unprecedented jatrophane-derived
diterpenoid esters with a novel 5/6/4/6-fused tetracyclic ring skeleton, were
isolated from the whole plants of Euphorbia helioscopia. The structures of 1 and
2 were elucidated by extensive spectroscopic methods and electronic circular
dichroism (ECD) analyses. The plausible biogenetic pathways of 1 and 2 were
postulated. 1 and 2 were found to be potent inhibitors of P-glycoprotein (ABCB1)
and 1 also exhibited cytotoxicity against MDA-MB-231 cell lines.
PMID- 28687753
TI - Development of Novel Mouse Model of Ulcers Induced by Implantation of Magnets.
AB - We developed a novel mouse model of human refractory cutaneous ulcers that more
faithfully reflects pathology and evaluated the effects of mixed cell sheets
comprising peripheral blood mononuclear cells and fibroblasts, which we
previously developed for treating refractory cutaneous ulcers. Model development
involved sandwiching the skin between two magnets, one of which was implanted
under the skin for 7 consecutive days. This magnet-implanted ulcer model produced
persistently large amounts of exudate and induced the infiltration of the ulcer
with inflammatory cells. The model mice had a thicker epidermis and impaired
transforming growth factor-beta (TGF-beta) signaling followed by SMAD2 down
regulation, which causes epidermal hyperplasia in chronic ulcers. Impaired TGF
beta signaling also occurred in the ulcers of critical limb ischemia patients.
Mixed cell implantation in this ulcer model reduced TNF-alpha and IL-6 levels in
the tissues surrounding the mixed cell sheet-treated ulcers compared with
controls or mice treated with trafermin (FGF2). Seven days after commencing
therapy, the epidermis was thinner in mice treated with the mixed cell sheets
than in controls. This model may therefore serve as a clinically relevant model
of human ulcers, and our mixed cell sheets may effectively relieve chronic
inflammation and inhibit refractoriness mechanisms.
PMID- 28687754
TI - DNA Barcoding studies on Thrips in India: Cryptic species and Species complexes.
AB - Thrips are one of the major sucking pest and vector of plant viruses causing huge
economic loss in agriculture. The accurate identification of thrips is crucial
for effective pest management strategies. However, morphology based
identification has limitations and warrants integration of molecular data. We
attempted the largest DNA barcoding initiative on 370 sequences of 89 thrips
morphospecies including 104 novel sequences from 39 morphospecies, including the
type specimens of four species. The results of multiple species delimitation
methods (BIN, ABGD, GMYC and bPTP) were consistent for 73 species (82%) with
their morphological identifications. A total of 107 molecular operational
taxonomic units (MOTUs) was recovered for 89 morphospecies by superimposing
multiple methods and applying a three level nomenclature system. We detected more
than one MOTU in 14 morphospecies indicating to have cryptic diversity including,
two major vector species (Frankliniella schultzei and Thrips palmi). However,
four morphospecies (Thrips moundi, Thrips carthami, Haplothrips andersi and
Haplothrips gowdeyi) showed low genetic distances between them with overlapping
in barcode gap that requires further analysis with multiple molecular markers and
more specimens from wide geographical areas for better taxonomic judgment. We
also presented the advantage of simultaneous use of multiple delimitation methods
for detection and identification of cryptic species.
PMID- 28687755
TI - The integrated pathway of TGFbeta/Snail with TNFalpha/NFkappaB may facilitate the
tumor-stroma interaction in the EMT process and colorectal cancer prognosis.
AB - Substantial evidence has shown that epithelial-mesenchymal transition (EMT) plays
critical roles in colorectal cancer (CRC) development and prognosis. To uncover
the pivotal regulators that function in the cooperative interactions between
cancer cells and their microenvironment and consequently affect the EMT process,
we carried out a systematic analysis and evaluated prognosis in CRC specimens.
Tumor buds and their surrounding stroma were captured using laser
microdissection. We used gene expression profiling, bioinformatics analysis and
regulatory network construction for molecular selection. The clinical
significance of potential biomarkers was investigated. We identified potential
EMT biomarkers, including BGN, MMP1, LGALS1, SERPINB5, and TM4SF4, all of which
participated in the integrated pathway of TGFbeta/Snail with TNFalpha/NFkappaB.
We also found that BGN, MMP1, LGALS1, SERPINB5 and TM4SF4 were related to CRC
patient prognosis. Patients with higher expression of these individual potential
biomarkers had poorer prognosis. Among the identified biomarkers, BGN and TM4SF4
are reported, for the first time, to probably be involved in the EMT process and
to predict CRC prognosis. Our results strongly suggest that the integrated
pathway of TGFbeta/Snail with TNFalpha/NFkappaB may be the principal axis that
links cancer cells to their microenvironment during the EMT process and results
in poor prognosis in CRC patients.
PMID- 28687756
TI - John's Equation-based Consistency Condition and Corrupted Projection Restoration
in Circular Trajectory Cone Beam CT.
AB - In transmitted X-ray tomography imaging, the acquired projections may be
corrupted for various reasons, such as defective detector cells and beam-stop
array scatter correction problems. In this study, we derive a consistency
condition for cone-beam projections and propose a method to restore lost data in
corrupted projections. In particular, the relationship of the geometry parameters
in circular trajectory cone-beam computed tomography (CBCT) is utilized to
convert an ultra-hyperbolic partial differential equation (PDE) into a second
order PDE. The second-order PDE is then transformed into a first-order ordinary
differential equation in the frequency domain. The left side of the equation for
the newly derived consistency condition is the projection derivative of the
current and adjacent views, whereas the right side is the projection derivative
of the geometry parameters. A projection restoration method is established based
on the newly derived equation to restore corrupted data in projections in
circular trajectory CBCT. The proposed method is tested in beam-stop array
scatter correction, metal artifact reduction, and abnormal pixel correction cases
to evaluate the performance of the consistency condition and corrupted projection
restoration method. Qualitative and quantitative results demonstrate that the
present method has considerable potential in restoring lost data in corrupted
projections.
PMID- 28687757
TI - Fate and Transport of Shale-derived, Biogenic Methane.
AB - Natural gas extraction from unconventional shale gas reservoirs is the subject of
considerable public debate, with a key concern being the impact of leaking
fugitive natural gases on shallow potable groundwater resources. Baseline data
regarding the distribution, fate, and transport of these gases and their isotopes
through natural formations prior to development are lacking. Here, we define the
migration and fate of CH4 and delta13C-CH4 from an early-generation bacterial gas
play in the Cretaceous of the Williston Basin, Canada to the water table. Our
results show the CH4 is generated at depth and diffuses as a conservative species
through the overlying shale. We also show that the diffusive fractionation of
delta13C-CH4 (following glaciation) can complicate fugitive gas interpretations.
The sensitivity of the delta13C-CH4 profile to glacial timing suggests it may be
a valuable tracer for characterizing the timing of geologic changes that control
transport of CH4 (and other solutes) and distinguishing between CH4 that rapidly
migrates upward through a well annulus or other conduit and CH4 that diffuses
upwards naturally. Results of this study were used to provide recommendations for
designing baseline investigations.
PMID- 28687758
TI - Directional Exosome Proteomes Reflect Polarity-Specific Functions in Retinal
Pigmented Epithelium Monolayers.
AB - The retinal pigmented epithelium (RPE) forms the outer blood-retinal barrier in
the eye and its polarity is responsible for directional secretion and uptake of
proteins, lipoprotein particles and extracellular vesicles (EVs). Such a
secretional division dictates directed interactions between the systemic
circulation (basolateral) and the retina (apical). Our goal is to define the
polarized proteomes and physical characteristics of EVs released from the RPE.
Primary cultures of porcine RPE cells were differentiated into polarized RPE
monolayers on permeable supports. EVs were isolated from media bathing either
apical or basolateral RPE surfaces, and two subpopulations of small EVs including
exosomes, and dense EVs, were purified and processed for proteomic profiling. In
parallel, EV size distribution and concentration were determined. Using protein
correlation profiling mass spectrometry, a total of 631 proteins were identified
in exosome preparations, 299 of which were uniquely released apically, and 94
uniquely released basolaterally. Selected proteins were validated by Western
blot. The proteomes of these exosome and dense EVs preparations suggest that
epithelial polarity impacts directional release. These data serve as a foundation
for comparative studies aimed at elucidating the role of exosomes in the
molecular pathophysiology of retinal diseases and help identify potential
therapeutic targets and biomarkers.
PMID- 28687759
TI - Emerging patterns of plasmid-host coevolution that stabilize antibiotic
resistance.
AB - Multidrug resistant bacterial pathogens have become a serious global human health
threat, and conjugative plasmids are important drivers of the rapid spread of
resistance to last-resort antibiotics. Whereas antibiotics have been shown to
select for adaptation of resistance plasmids to their new bacterial hosts, or
vice versa, a general evolutionary mechanism has not yet emerged. Here we
conducted an experimental evolution study aimed at determining general patterns
of plasmid-bacteria evolution. Specifically, we found that a large conjugative
resistance plasmid follows the same evolutionary trajectories as its non
conjugative mini-replicon in the same and other species. Furthermore, within a
single host-plasmid pair three distinct patterns of adaptive evolution led to
increased plasmid persistence: i) mutations in the replication protein gene
(trfA1); ii) the acquisition by the resistance plasmid of a transposon from a co
residing plasmid encoding a putative toxin-antitoxin system; iii) a mutation in
the host's global transcriptional regulator gene fur. Since each of these
evolutionary solutions individually have been shown to increase plasmid
persistence in other plasmid-host pairs, our work points towards common
mechanisms of plasmid stabilization. These could become the targets of future
alternative drug therapies to slow down the spread of antibiotic resistance.
PMID- 28687760
TI - Hypofractionated stereotactic radiation therapy activates the peripheral immune
response in operable stage I non-small-cell lung cancer.
AB - It has been reported that in patients with operable stage I non-small cell lung
cancer (NSCLC), overall survival (OS) is better in those who undergo
hypofractionated stereotactic radiation therapy (HSRT) than in those who undergo
surgery. However, the reason that HSRT has a better OS has not been fully
explored. Here, we analyzed reconstitution kinetics in immune cells in the
peripheral blood of NSCLC patients after HSRT. We found that HSRT increased the
frequency of total T cells, especially the proportion of CD8+ T cells, but
decreased the frequency of inhibitory Tregs. Intracellular staining showed that
after HSRT, peripheral CD8+ T cells were transformed into activated T cells,
which express high levels of TNF-alpha, IFN-gamma, granzyme B and IL-2. HSRT also
increased the production of IL-2, TNF-alpha, and IFN-gamma but down-regulated the
production of TGF-beta in CD4+ T cells. The frequencies of naive B cells and
double-negative B cells were lower, while the proportions of MZ-like B cells,
transitional B cells and plasmablast cells were higher after HSRT. Collectively,
our results demonstrate that HSRT activates the peripheral immune response and
indicate the dynamic variation in peripheral lymphocytes after HSRT, which is
very important for optimizing combination treatments in clinical practice.
PMID- 28687761
TI - Inactivation of Pol theta and C-NHEJ eliminates off-target integration of
exogenous DNA.
AB - Off-target or random integration of exogenous DNA hampers precise genomic
engineering and presents a safety risk in clinical gene therapy strategies.
Genetic definition of random integration has been lacking for decades. Here, we
show that the A-family DNA polymerase theta (Pol theta) promotes random
integration, while canonical non-homologous DNA end joining plays a secondary
role; cells double deficient for polymerase theta and canonical non-homologous
DNA end joining are devoid of any integration events, demonstrating that these
two mechanisms define random integration. In contrast, homologous recombination
is not reduced in these cells and gene targeting is improved to 100% efficiency.
Such complete reversal of integration outcome, from predominately random
integration to exclusively gene targeting, provides a rational way forward to
improve the efficacy and safety of DNA delivery and gene correction
approaches.Random off-target integration events can impair precise gene targeting
and poses a safety risk for gene therapy. Here the authors show that repression
of polymerase theta and classical non-homologous recombination eliminates random
integration.
PMID- 28687762
TI - X-Ray snapshots of a pyridoxal enzyme: a catalytic mechanism involving concerted
[1,5]-hydrogen sigmatropy in methionine gamma-lyase.
AB - Pyridoxal 5'-phosphate (PLP)-enzymes are essentially involved in amino acid and
amine metabolism of a wide variety of organisms. Despite their extensive
biochemical studies, there are little evidence and structural data to
comprehensively elaborate the catalytic mechanism. We obtained X-ray snapshots of
l-methionine gamma-lyase from Entamoeba histolytica (EhMGL), a PLP-enzyme
catalyzing the gamma-elimination reaction of methionine. Here, we suggest a
catalytic mechanism of EhMGL by using the X-ray snapshots covering all stages of
this multistep catalysis reaction. Initial formation of a Michaelis complex is
followed by the migration of double bond from the C4'=Nalpha-Calpha moiety in an
intermediate PLP-methionine imine to C4'-Nalpha=Calpha in pyridoxamine 5'
phosphate (PMP)-alpha,beta-dehydromethionine imine without intervention of a
putative quinonoid intermediate. The enzyme can facilitate the subsequent gamma
elimination of methanethiol by the possible general acid-base catalysis of Tyr108
for the E1cB mechanism, enabling to form the ene-imine C4'-Nalpha=Calpha
Cbeta=Cgamma structure with the s-cis conformation, which is prerequisite for the
non-enzymatic symmetry-allowed suprafacial [1,5]-hydrogen shift to complete the
catalytic cycle by releasing alpha-ketobutyrate. The mechanism based on the X-ray
snapshots is consistent with the reactivity of MGL toward methionine analogues.
The generality of such a mechanism involving non-enzymatic concerted reaction in
other PLP enzymes is discussed.
PMID- 28687764
TI - Impacts of increasing typhoons on the structure and function of a subtropical
forest: reflections of a changing climate.
AB - Due to their destructive and sporadic nature, it is often difficult to evaluate
and predict the effects of typhoon on forest ecosystem patterns and processes. We
used a 21-yr record of litterfall rates to explore the influence of typhoon
frequency and intensity, along with other meteorological variables, on ecosystem
dynamics in a subtropical rainforest. Over the past half century there has been
an increasing frequency of strong typhoons (category 3; >49.6 m s-1; increase of
1.5 typhoons/decade) impacting the Fushan Experimental Forest, Taiwan. At Fushan
strong typhoons drive total litterfall mass with an average of 1100 kg ha-1
litterfall typhoon-1. While mean typhoon season litterfall has been observed to
vary by an order of magnitude, mean litterfall rates associated with annual leaf
senescence vary by <20%. In response to increasing typhoon frequency, total
annual litter mass increased gradually over the 21-year record following three
major typhoons in 1994. Monthly maximum wind speed was predictive of monthly
litterfall, yet the influence of precipitation and temperature was only evident
in non-typhoon affected months. The response of this subtropical forest to strong
typhoons suggests that increasing typhoon frequency has already shifted ecosystem
structure and function (declining carbon sequestration and forest stature).
PMID- 28687763
TI - A tyrosine aminotransferase involved in rosmarinic acid biosynthesis in Prunella
vulgaris L.
AB - Rosmarinic acid (RA) and its derivants are medicinal compounds that comprise the
active components of several therapeutics. We isolated and characterised a
tyrosine aminotransferase of Prunella vulgaris (PvTAT). Deduced PvTAT was
markedly homologous to other known/putative plant TATs. Cytoplasmic localisation
of PvTAT was observed in tobacco protoplasts. Recombinantly expressed and
purified PvTAT had substrates preference for L-tyrosine and phenylpyruvate, with
apparent K m of 0.40 and 0.48 mM, and favoured the conversion of tyrosine to 4
hydroxyphenylpyruvate. In vivo activity was confirmed by functional restoration
of the Escherichia coli tyrosine auxotrophic mutant DL39. Agrobacterium
rhizogenes-mediated antisense/sense expression of PvTAT in hairy roots was used
to evaluate the contribution of PvTAT to RA synthesis. PvTAT were reduced by 46
95% and RA were decreased by 36-91% with low catalytic activity in antisense
transgenic hairy root lines; furthermore, PvTAT were increased 0.77-2.6-fold with
increased 1.3-1.8-fold RA and strong catalytic activity in sense transgenic hairy
root lines compared with wild-type counterparts. The comprehensive physiological
and catalytic evidence fills in the gap in RA-producing plants which didn't
provide evidence for TAT expression and catalytic activities in vitro and in
vivo. That also highlights RA biosynthesis pathway in P. vulgaris and provides
useful information to engineer natural products.
PMID- 28687765
TI - Reduction of epileptiform activity in ketogenic mice: The role of monocarboxylate
transporters.
AB - Epilepsy is a chronic neurological disorder that affects approximately 50 million
people worldwide. Ketogenic diet (KD) can be a very effective treatment for
intractable epilepsy. Potential mechanisms of action for KD have been proposed,
including the re-balance among excitatory and inhibitory neurotransmission and
decrease in the glycolytic rate in brain cells. KD has been shown to have an
effect on the expression pattern of monocarboxylate transporters (MCT), however,
it is unknown whether MCT transport activity is affected by KD and linked to the
reduction of seizures during KD. Therefore, we studied the influence of KD on MCT
transport activity and the role of MCTs during epileptiform activity. Our results
showed a decrease in the epileptiform activity in cortical slices from mice fed
on KD and in the presence of beta-hydroxybutyrate. KD increased transport
capacity for ketone bodies and lactate in cortical astrocytes by raising the MCT1
expression level. Inhibition of MCT1 and MCT2 in control conditions decreases
epileptiform activity, while in KD it induced an increase in epileptiform
activity. Our results suggest that MCTs not only play an important role in the
transport of ketone bodies, but also in the modulation of brain energy metabolism
under normal and ketogenic conditions.
PMID- 28687766
TI - Biochemical properties of GH94 cellodextrin phosphorylase THA_1941 from a
thermophilic eubacterium Thermosipho africanus TCF52B with cellobiose
phosphorylase activity.
AB - A hypothetic gene (THA_1941) encoding a putative cellobiose phosphorylase (CBP)
from Thermosipho africanus TCF52B has very low amino acid identities (less than
12%) to all known GH94 enzymes. This gene was cloned and over-expressed in
Escherichia coli BL21(DE3). The recombinant protein was hypothesized to be a CBP
enzyme and it showed an optimum temperature of 75 degrees C and an optimum pH of
7.5. Beyond its CBP activity, this enzyme can use cellobiose and long-chain
cellodextrins with a degree of polymerization of greater than two as a glucose
acceptor, releasing phosphate from glucose 1-phosphate. The catalytic
efficiencies (k cat/K m) indicated that cellotetraose and cellopentaose were the
best substrates for the phosphorolytic and reverse synthetic reactions,
respectively. These results suggested that this enzyme was the first enzyme
having both cellodextrin and cellobiose phosphorylases activities. Because it
preferred cellobiose and cellodextrins to glucose in the synthetic direction, it
was categorized as a cellodextrin phosphorylase (CDP). Due to its unique ability
of the reverse synthetic reaction, this enzyme could be a potential catalyst for
the synthesis of various oligosaccharides. The speculative function of this CDP
in the carbohydrate metabolism of T. africanus TCF52B was also discussed.
PMID- 28687767
TI - The Power of mind: Blocking visual perception by hypnosis.
AB - The present study investigated the effects of suggestion on the processing of
visual stimuli. Participants counted rare visual stimuli presented on a screen,
once during a hypnosis condition where they were suggested that their vision of
the screen is blocked by a virtual wooden board in front of their eyes and once
during a control condition without suggestion. In the hypnosis condition,
counting performance was about 20% worse than in the control condition. At the
same time, the P3b amplitude of the event-related brain potential was about 37%
reduced. Smaller P3b amplitudes were significantly associated with deficient
counting performance, and this effect was largest in participants who reported
the blockade as real. In contrast, earlier brain responses (N1, P2) that reflect
basic processing of the visual stimuli were not affected by the suggested
blockade. We conclude that the suggestion of the blockade affects later stages of
visual perception, leaving early processes intact. This illustrates the impact of
suggestions and the power of mind.
PMID- 28687768
TI - Barbier-type anti-Diastereo- and Enantioselective Synthesis of beta
Trimethylsilyl, Fluorinated Methyl, Phenylthio Homoallylic Alcohols.
AB - Catalytic Asymmetric allylation of aldehydes with functionalized allylic reagents
represents an important process in synthetic organic chemistry because the
resulting chiral homoallylic alcohols are valuable building blocks in diverse
research fields. Despite the obvious advantages of allyl halides as allylation
reagent under Barbier-type conditions, catalytic asymmetric version using
functionalized allyl halides remains largely underdeveloped. Here, we addressed
this issue by employing a chromium-catalysis system. The use of readily available
allyl bromides with gamma substitutions including trimethylsilyl, fluorinated
methyl and phenylthio groups provided an efficient and convenient method to
introduce those privileged functionalities into homoallylic alcohols. Good
yields, high anti-diastereo- and excellent enantioselectivities were achieved
under mild reaction conditions.
PMID- 28687770
TI - Elastic properties of superconductors and materials with weakly correlated spins.
AB - It is shown that in the ergodic regime, the temperature dependence of Young's
modulus is solely determined by the magnetic properties of a material. For the
large class of materials with paramagnetic or diamagnetic response, simple
functional forms of the temperature derivative of Young's modulus are derived and
compared with experimental data and empirical results. Superconducting materials
in the Meissner phase are ideal diamagnets. As such, they display remarkable
elastic properties. Constant diamagnetic susceptibility gives rise to a
temperature independent elastic modulus for ceramic and single crystalline
superconductors alike. The thermodynamic approach established in this report,
paves the way to tailor elastic material parameters through the design of
magnetic properties.
PMID- 28687769
TI - Computational sensing of herpes simplex virus using a cost-effective on-chip
microscope.
AB - Caused by the herpes simplex virus (HSV), herpes is a viral infection that is one
of the most widespread diseases worldwide. Here we present a computational
sensing technique for specific detection of HSV using both viral immuno
specificity and the physical size range of the viruses. This label-free approach
involves a compact and cost-effective holographic on-chip microscope and a
surface-functionalized glass substrate prepared to specifically capture the
target viruses. To enhance the optical signatures of individual viruses and
increase their signal-to-noise ratio, self-assembled polyethylene glycol based
nanolenses are rapidly formed around each virus particle captured on the
substrate using a portable interface. Holographic shadows of specifically
captured viruses that are surrounded by these self-assembled nanolenses are then
reconstructed, and the phase image is used for automated quantification of the
size of each particle within our large field-of-view, ~30 mm2. The combination of
viral immuno-specificity due to surface functionalization and the physical size
measurements enabled by holographic imaging is used to sensitively detect and
enumerate HSV particles using our compact and cost-effective platform. This
computational sensing technique can find numerous uses in global health related
applications in resource-limited environments.
PMID- 28687771
TI - Prominent metallic surface conduction and the singular magnetic response of
topological Dirac fermion in three-dimensional topological insulator
Bi1.5Sb0.5Te1.7Se1.3.
AB - We report semiconductor to metal-like crossover in the temperature dependence of
resistivity (rho) due to the switching of charge transport from bulk to surface
channel in three-dimensional topological insulator Bi1.5Sb0.5Te1.7Se1.3. Unlike
earlier studies, a much sharper drop in rho(T) is observed below the crossover
temperature due to the dominant surface conduction. Remarkably, the resistivity
of the conducting surface channel follows a rarely observable T 2 dependence at
low temperature, as predicted theoretically for a two-dimensional Fermi liquid
system. The field dependence of magnetization shows a cusp-like paramagnetic peak
in the susceptibility (chi) at zero field over the diamagnetic background. The
peak is found to be robust against temperature and chi decays linearly with the
field from its zero-field value. This unique behavior of the chi is associated
with the spin-momentum locked topological surface state in Bi1.5Sb0.5Te1.7Se1.3.
The reconstruction of the surface state with time is clearly reflected through
the reduction of the peak height with the age of the sample.
PMID- 28687772
TI - Improving the electrocatalytic properties of Pd-based catalyst for direct alcohol
fuel cells: effect of solid solution.
AB - The tolerance of the electrode against the CO species absorbed upon the surface
presents the biggest dilemma of the alcohol fuel cells. Here we report for the
first time that the inclusion of (Zr, Ce)O2 solid solution as the supporting
material can significantly improve the anti-CO-poisoning as well as the activity
of Pd/C catalyst for ethylene glycol electro-oxidation in KOH medium. In
particular, the physical origin of the improved electrocatalytic properties has
been unraveled by first principle calculations. The 3D stereoscopic Pd cluster on
the surface of (Zr, Ce)O2 solid solution leads to weaker Pd-C bonding and smaller
CO desorption driving force. These results support that the Pd/ZrO2-CeO2/C
composite catalyst could be used as a promising effective candidate for direct
alcohol fuel cells application.
PMID- 28687773
TI - Topological delocalization and tuning of surface channel separation in Bi2Se2Te
Topological Insulator Thin films.
AB - The surface states of a 3D topological insulator (TI) exhibit topological
protection against backscattering. However, the contribution of bulk electrons to
the transport data is an impediment to the topological protection of surface
states. We report the tuning of the chemical potential in the bulk in Bi2Se2Te TI
thin films, pinning it near the center of the bulk band gap, thereby suppressing
the bulk carriers. The temperature dependent resistance of these films show
activated behavior down to 50 K, followed by a metallic transition at lower
temperatures, a hallmark of robustness of TI surface states. Manifestation of
topological protection and surface dominated transport is explained by 2D weak
antilocalization phenomenon. We further explore the effect of surface to bulk
coupling in TI in this work, which is captured by the number of effective
conducting surface channels that participate in the transport. The presence of a
single conducting channel indicates a strong surface to bulk coupling which is
detrimental to purely topological transport. We demonstrate the decoupling of
topological surface states on opposite surfaces of thin films, thereby
suppressing the bulk transport. Our findings provide a deeper understanding of
surface to bulk coupling along with topological transport behavior and their
respective tunability.
PMID- 28687774
TI - Andean Mountain Building Did not Preclude Dispersal of Lowland Epiphytic Orchids
in the Neotropics.
AB - The Andean uplift is one of the major orographic events in the New World and has
impacted considerably the diversification of numerous Neotropical lineages.
Despite its importance for biogeography, the specific role of mountain ranges as
a dispersal barrier between South and Central American lowland plant lineages is
still poorly understood. The swan orchids (Cycnoches) comprise ca 34 epiphytic
species distributed in lowland and pre-montane forests of Central and South
America. Here, we study the historical biogeography of Cycnoches to better
understand the impact of the Andean uplift on the diversification of Neotropical
lowland plant lineages. Using novel molecular sequences (five nuclear and plastid
regions) and twelve biogeographic models, we infer that the most recent common
ancestor of Cycnoches originated in Amazonia ca 5 Mya. The first colonization of
Central America occurred from a direct migration event from Amazonia, and
multiple bidirectional trans-Andean migrations between Amazonia and Central
America took place subsequently. Notably, these rare biological exchanges
occurred well after major mountain building periods. The Andes have limited plant
migration, yet it has seldom allowed episodic gene exchange of lowland epiphyte
lineages such as orchids with great potential for effortless dispersal because of
the very light, anemochorous seeds.
PMID- 28687775
TI - Integrated analysis of tobacco miRNA and mRNA expression profiles under PVY
infection provids insight into tobacco-PVY interactions.
AB - Potato virus Y (PVY) is a globally and economically important pathogen of potato,
tobacco, tomato and other staple crops and caused significant yield losses and
reductions in quality.To explore the molecular PVY-host interactions, we analysed
changes in the miRNA and mRNA profiles of tobacco in response to PVY infection. A
total of 81 differentially expressed miRNAs belonging to 29 families and 8133
mRNAs were identified. The Gene Ontology (GO) enrichment analyses showed that
genes encoding the DNA/RNA binding, catalytic activity and signalling molecules
were all significantly enriched. Moreover, 88 miRNA-mRNA interaction pairs were
identified through a combined analysis of the two datasets. We also found
evidence showing that the virus-derived siRNAs (vsiRNAs) from the PVY genome
target tobacco translationally controlled tumor protein (NtTCTP) mRNA and mediate
plant resistance to PVY. Together, our findings revealed that both miRNA and mRNA
expression patterns can be changed in response to PVY infection and novel vsiRNA
plant interactions that may regulate plant resistance to PVY. Both provide fresh
insights into the virus-plant interactions.
PMID- 28687776
TI - Network Structure Explains the Impact of Attitudes on Voting Decisions.
AB - Attitudes can have a profound impact on socially relevant behaviours, such as
voting. However, this effect is not uniform across situations or individuals, and
it is at present difficult to predict whether attitudes will predict behaviour in
any given circumstance. Using a network model, we demonstrate that (a) more
strongly connected attitude networks have a stronger impact on behaviour, and (b)
within any given attitude network, the most central attitude elements have the
strongest impact. We test these hypotheses using data on voting and attitudes
toward presidential candidates in the US presidential elections from 1980 to
2012. These analyses confirm that the predictive value of attitude networks
depends almost entirely on their level of connectivity, with more central
attitude elements having stronger impact. The impact of attitudes on voting
behaviour can thus be reliably determined before elections take place by using
network analyses.
PMID- 28687777
TI - Tunable magnetization and damping of sputter-deposited, exchange coupled Py|Fe
bilayers.
AB - We report on magnetic damping of exchange coupled, polycrystalline
Py(Ni80Fe20)|Fe and Fe|Py bilayers, prepared by sputter-deposition on an
amorphous 3 nm Ta seed layer. FMR measurements are performed on varying
thicknesses of the individual Py and Fe layers while keeping the total bilayer
structure thickness fixed. When Fe is grown directly on Ta, there is large
magnetic inhomogeneity and damping. However, when a Py layer is deposited between
Fe and Ta, both the magnetic inhomogeneity and damping significantly decrease
even if Fe is covered by Ta. The intrinsic damping of the Ta|Py|Fe film can be
further lowered by increasing the Fe to Py ratio. SQUID measurements show a
linear increase in saturation magnetization with increasing ratio of Fe to Py. A
combination of in-plane and out-of-plane X-ray diffraction measurements show that
Py is textured along the <111> directions and Fe is textured along the <110>,
with Fe texture significantly improving if it is deposited on Ta|Py instead of
Ta. By improving the texture of Fe by introducing a thin Py layer between Fe and
Ta, one can grow Fe thin films with zero in-plane anisotropy, tunable magnetic
moment, and low magnetic damping, approaching that of the best single crystal Fe.
PMID- 28687778
TI - Evolution of the Araliaceae family inferred from complete chloroplast genomes and
45S nrDNAs of 10 Panax-related species.
AB - We produced complete sequences and conducted comparative analysis of the
maternally inherited chloroplast (cp) genomes and bi-parentally inherited 45S
nuclear ribosomal RNA genes (nrDNA) from ten Araliaceae species to elucidate the
genetic diversity and evolution in that family. The cp genomes ranged from
155,993 bp to 156,730 bp with 97.1-99.6% similarity. Complete 45S nrDNA units
were about 11 kb including a 5.8-kb 45S cistron. Among 79 cp protein-coding
genes, 74 showed nucleotide variations among ten species, of which infA, rpl22,
rps19 and ndhE genes showed the highest Ks values and atpF, atpE, ycf2 and rps15
genes showed the highest Ka/Ks values. Four genes, petN, psaJ, psbF, and psbN,
related to photosynthesis and one gene, rpl23, related to the ribosomal large
subunit remain conserved in all 10 Araliaceae species. Phylogenetic analysis
revealed that the ten species could be resolved into two monophyletic lineages,
the Panax-Aralia and the Eleutherococcus-Dendropanax groups, which diverged
approximately 8.81-10.59 million years ago (MYA). The Panax genus divided into
two groups, with diploid species including P. notoginseng, P. vietnamensis, and
P. japonicus surviving in Southern Asia and a tetraploid group including P.
ginseng and P. quinquefolius Northern Asia and North America 2.89-3.20 MYA.
PMID- 28687779
TI - Potential risk of re-emergence of urban transmission of Yellow Fever virus in
Brazil facilitated by competent Aedes populations.
AB - Yellow fever virus (YFV) causing a deadly viral disease is transmitted by the
bite of infected mosquitoes. In Brazil, YFV is restricted to a forest cycle
maintained between non-human primates and forest-canopy mosquitoes, where humans
can be tangentially infected. Since late 2016, a growing number of human cases
have been reported in Southeastern Brazil at the gates of the most populated
areas of South America, the Atlantic coast, with Rio de Janeiro state hosting
nearly 16 million people. We showed that the anthropophilic mosquitoes Aedes
aegypti and Aedes albopictus as well as the YFV-enzootic mosquitoes Haemagogus
leucocelaenus and Sabethes albiprivus from the YFV-free region of the Atlantic
coast were highly susceptible to American and African YFV strains. Therefore, the
risk of reemergence of urban YFV epidemics in South America is major with a virus
introduced either from a forest cycle or by a traveler returning from the YFV
endemic region of Africa.
PMID- 28687780
TI - Nuclear receptors connect progenitor transcription factors to cell cycle control.
AB - The specification and growth of organs is controlled simultaneously by networks
of transcription factors. While the connection between these transcription
factors with fate determinants is increasingly clear, how they establish the link
with the cell cycle is far less understood. Here we investigate this link in the
developing Drosophila eye, where two transcription factors, the MEIS1 homologue
hth and the Zn-finger tsh, synergize to stimulate the proliferation of naive eye
progenitors. Experiments combining transcriptomics, open-chromatin profiling,
motif analysis and functional assays indicate that these progenitor transcription
factors exert a global regulation of the proliferation program. Rather than
directly regulating cell cycle genes, they control proliferation through an
intermediary layer of nuclear receptors of the ecdysone/estrogen-signaling
pathway. This regulatory subnetwork between hth, tsh and nuclear receptors might
be conserved from Drosophila to mammals, as we find a significant co
overexpression of their human homologues in specific cancer types.
PMID- 28687781
TI - P2X7 receptor antagonism modulates IL-1beta and MMP9 in human atherosclerotic
vessels.
AB - In atherosclerosis, matrix metallopeptidases (MMPs) contribute to plaque rupture
through weakening of the fibrous cap. Pleiotropic P2X purinoceptor 7 (P2X7),
expressed in the carotid plaque (PL), is involved in interleukin 1 beta (IL
1beta) release that may influence MMP9 generation, thus their possible modulation
through acting on P2X7 was investigated. P2X7-related machinery was characterized
and the effects of P2X7 antagonists (A740003, KN62) and MMPs inhibitors
(Batimastat, Ro28-2653) were studied in ex-vivo tissue cultures of human PL's vs.
non-atherosclerotic internal mammary artery (IMA) by using molecular biology,
immune-biochemical and microscopy methodologies. We highlighted atherosclerosis
related differences between PLs and IMAs molecular patterns, and their
responsivity to P2X7 antagonism. High IL-1beta tissue content was associated with
PLs morphology and instability/vulnerability. We demonstrated that A740003, but
not KN62, decreased IL-1beta and MMP9 independently from NLR family pyrin domain
containing 3, but in relationship with patient's smoking status. Acting
downstream P2X7 by MMPs inhibitors, diminished IL-1beta mRNA without
transcriptional effect at MMP9, possibly because the assumption of statin by
patients. These data firstly demonstrated A740003 suitability as a specific tool
to decrease inflammatory status in human vessels and might support the design of
studies applying P2X7 antagonists for the local targeting and tailored therapy of
atherosclerosis.
PMID- 28687782
TI - Human Cochlear Histopathology Reflects Clinical Signatures of Primary Neural
Degeneration.
AB - Auditory neuropathy is a significant and understudied cause of human hearing
loss, diagnosed in patients who demonstrate abnormal function of the cochlear
nerve despite typical function of sensory cells. Because the human inner ear
cannot be visualized during life, histopathological analysis of autopsy specimens
is critical to understanding the cellular mechanisms underlying this pathology.
Here we present statistical models of severe primary neuronal degeneration and
its relationship to pure tone audiometric thresholds and word recognition scores
in comparison to age-matched control patients, spanning every decade of life.
Analysis of 30 ears from 23 patients shows that severe neuronal loss correlates
with elevated audiometric thresholds and poor word recognition. For each ten
percent increase in total neuronal loss, average thresholds across patients at
each audiometric test frequency increase by 6.0 dB hearing level (HL). As
neuronal loss increases, threshold elevation proceeds more rapidly in low
audiometric test frequencies than in high frequencies. Pure tone average closely
agrees with word recognition scores in the case of severe neural pathology.
Histopathologic study of the human inner ear continues to emphasize the need for
non- or minimally invasive clinical tools capable of establishing cellular-level
diagnoses.
PMID- 28687783
TI - Serum TFF1 and TFF3 but not TFF2 are higher in women with breast cancer than in
women without breast cancer.
AB - Breast cancer remains a common malignancy in women, but the take-up for breast
cancer screening programs in Japan is still low, possibly due to its perceived
inconvenience. TFF1 and TFF3 are expressed in both breast cancer tissue and
normal breast. Serum trefoil proteins were reported as cancer screening markers
for gastric, prostate, lung, pancreatic cancer and cholangio carcinoma. The
purpose of this study was to examine whether serum trefoil proteins could be
screening biomarkers for breast cancer. Serum trefoil proteins in 94 breast
cancer patients and 84 health check females were measured by ELISA. Serum TFF1
and TFF3 were significantly higher and serum TFF2 was significantly lower in
breast cancer patients. Area under the curve of receiver operating characteristic
of TFF1, TFF2, and TFF3 was 0.69, 0.83, and. 0.72, respectively. AUC of the
combination of TFF1, TFF2, and TFF3 was 0.96. Immunohistochemically, TFF1
expression was positive in 56.5% and TFF3 was positive in 73.9% of breast
cancers, while TFF2 was negative in all tumors. Serum TFF1 had positive
correlation with expression of TFF1 in breast cancer tissue. Serum concentrations
of TFF1 and TFF3 but not TFF2 are higher in women with breast cancer than in
women without breast cancer.
PMID- 28687784
TI - Whole transcriptome sequencing of Pseudomonas syringae pv. actinidiae-infected
kiwifruit plants reveals species-specific interaction between long non-coding RNA
and coding genes.
AB - An outbreak of kiwifruit bacterial canker disease caused by Pseudomonas syringae
pv. actinidiae (Psa) beginning in 2008 caused disaster to the kiwifruit industry.
However the mechanisms of interaction between kiwifruit and Psa are unknown. Long
noncoding RNAs (lncRNAs) are known to regulate many biological processes, but
comprehensive repertoires of kiwifruit lncRNAs and their effects on the
interaction between kiwifruit and Psa are unknown. Here, based on in-depth
transcriptomic analysis of four kiwifruit materials at three stages of infection
with Psa, we identified 14,845 transcripts from 12,280 loci as putative lncRNAs.
Hierarchical clustering analysis of differentially-expressed transcripts reveals
that both protein-coding and lncRNA transcripts are expressed species
specifically. Comparing differentially-expressed transcripts from different
species, variations in pattern-triggered immunity (PTI) were the main causes of
species-specific responses to infection by Psa. Using weighted gene co-expression
network analysis, we identified species-specific expressed key lncRNAs which were
closely related to plant immune response and signal transduction. Our results
illustrate that different kiwifruit species employ multiple different plant
immunity layers to fight against Psa infection, which causes distinct responses.
We also discovered that lncRNAs might affect kiwifruit responses to Psa
infection, indicating that both protein-coding regions and noncoding regions can
affect kiwifruit response to Psa infection.
PMID- 28687785
TI - Seed Pelleting with Calcium Peroxide Improves Crop Establishment of Direct-seeded
Rice under Waterlogging Conditions.
AB - Poor crop establishment of direct-seeded rice (DSR) is one of the major
constraints to wide adoption of DSR, particularly in areas prone to flooding
after sowing or where fields are not level. Seed pelleting is an effective,
practical and facile technique to enhance crop establishment under unfavorable
environmental conditions. To evaluate the effects of seed pelleting on rice
germination, seedling growth and associated metabolic events under waterlogging
stress, various seed pelleting treatments including formulae, pelleting times
(the weight ratio of pelleting agents: rice seeds = 1:1~7:1 (w/w) and CaO2
contents were tested in series of experiments. Naked seeds were maintained for
comparison as a control. Pelleting treatments with CaO2 significantly increased
seed germination and seedling growth of DSR under waterlogging conditions
compared with pelleted seeds without CaO2 and naked seeds. The optimum weight
ratios of CaO2 to dry seeds were found to be in the range of 0.6:1-1:1 based on
seed germination and seedling growth performance under waterlogging conditions.
Under waterlogging conditions, high seed germination percentage and vigorous
seedling growth of DSR due to seed pelleting with CaO2 was associated with an
increase in alpha-amylase activity, but decrease in alcohol dehydrogenase (ADH)
and pyruvate decarboxylase (PDC) activities in pelleted seeds.
PMID- 28687786
TI - Involvement of FANCD2 in Energy Metabolism via ATP5alpha.
AB - Growing evidence supports a general hypothesis that aging and cancer are diseases
related to energy metabolism. However, the involvement of Fanconi Anemia (FA)
signaling, a unique genetic model system for studying human aging or cancer, in
energy metabolism remains elusive. Here, we report that FA complementation group
D2 protein (FANCD2) functionally impacts mitochondrial ATP production through its
interaction with ATP5alpha, whereas this relationship was not observed in the
mutant FANCD2 (K561R)-carrying cells. Moreover, while ATP5alpha is present within
the mitochondria in wild-type cells, it is instead located mostly outside in
cells that carry the non-monoubiquitinated FANCD2. In addition, mitochondrial ATP
production is significantly reduced in these cells, compared to those cells
carrying wtFANCD2. We identified one region (AA42-72) of ATP5alpha, contributing
to the interaction between ATP5alpha and FANCD2, which was confirmed by protein
docking analysis. Further, we demonstrated that mtATP5alpha (?AA42-72) showed an
aberrant localization, and resulted in a decreased ATP production, similar to
what was observed in non-monoubiquitinated FANCD2-carrying cells. Collectively,
our study demonstrates a novel role of FANCD2 in governing cellular ATP
production, and advances our understanding of how defective FA signaling
contributes to aging and cancer at the energy metabolism level.
PMID- 28687787
TI - Quantum Nuclear Dynamics of Protons within Layered Hydroxides at High Pressure.
AB - Studies of the structure of hydroxides under pressure using neutron diffraction
reveal that the high concentration of hydrogen is distributed in a disordered
network. The disorder in the hydrogen-bond network and possible phase transitions
are reported to occur at pressures within the range accessible to experiments for
layered calcium hydroxides, which are considered to be exemplary prototype
materials. In this study, the static and dynamical properties of these layered
hydroxides are investigated using a quantum approach describing nuclear motion,
shown herein to be required particularly when studying diffusion processes
involving light hydrogen atoms. The effect of high-pressure on the disordered
hydrogen-bond network shows that the protons tunnel back and forth across the
barriers between three potential minima around the oxygen atoms. At higher
pressures the structure has quasi two-dimensional layers of hydrogen atoms, such
that at low temperatures this causes the barrier crossing of the hydrogen to be
significantly rarefied. Furthermore, for moderate values of both temperature and
pressure this process occurs less often than the usual mechanism of proton
transport via vacancies, limiting global proton diffusion within layers at high
pressure.
PMID- 28687789
TI - Identification of stacking faults in silicon carbide by polarization-resolved
second harmonic generation microscopy.
AB - Although silicon carbide is a highly promising crystalline material for a wide
range of electronic devices, extended and point defects which perturb the lattice
periodicity hold deep implications with respect to device reliability. There is
thus a great need for developing new methods that can detect silicon carbide
defects which are detrimental to device functionality. Our experiment
demonstrates that polarization-resolved second harmonic generation microscopy can
extend the efficiency of the "optical signature" concept as an all-optical rapid
and non-destructive set of investigation methods for the differentiation between
hexagonal and cubic stacking faults in silicon carbide. This technique can be
used for fast and in situ characterization and optimization of growth conditions
for epilayers of silicon carbide and similar materials.
PMID- 28687788
TI - First integrative trend analysis for a great ape species in Borneo.
AB - For many threatened species the rate and drivers of population decline are
difficult to assess accurately: species' surveys are typically restricted to
small geographic areas, are conducted over short time periods, and employ a wide
range of survey protocols. We addressed methodological challenges for assessing
change in the abundance of an endangered species. We applied novel methods for
integrating field and interview survey data for the critically endangered Bornean
orangutan (Pongo pygmaeus), allowing a deeper understanding of the species'
persistence through time. Our analysis revealed that Bornean orangutan
populations have declined at a rate of 25% over the last 10 years. Survival rates
of the species are lowest in areas with intermediate rainfall, where complex
interrelations between soil fertility, agricultural productivity, and human
settlement patterns influence persistence. These areas also have highest threats
from human-wildlife conflict. Survival rates are further positively associated
with forest extent, but are lower in areas where surrounding forest has been
recently converted to industrial agriculture. Our study highlights the urgency of
determining specific management interventions needed in different locations to
counter the trend of decline and its associated drivers.
PMID- 28687790
TI - Chronic inflammation triggered by the NLRP3 inflammasome in myeloid cells
promotes growth plate dysplasia by mesenchymal cells.
AB - Skeletal complications are common features of neonatal-onset multisystem
inflammatory disease (NOMID), a disorder caused by NLRP3-activating mutations.
NOMID mice in which NLRP3 is activated globally exhibit several characteristics
of the human disease, including systemic inflammation and cartilage dysplasia,
but the mechanisms of skeletal manifestations remain unknown. In this study, we
find that activation of NLRP3 in myeloid cells, but not mesenchymal cells
triggers chronic inflammation, which ultimately, causes growth plate and
epiphyseal dysplasia in mice. These responses are IL-1 signaling-dependent, but
independent of PARP1, which also functions downstream of NLRP3 and regulates
skeletal homeostasis. Mechanistically, inflammation causes severe anemia and
hypoxia in the bone environment, yet down-regulates the HIF-1alpha pathway in
chondrocytes, thereby promoting the demise of these cells. Thus, activation of
NLRP3 in hematopoietic cells initiates IL-1beta-driven paracrine cascades, which
promote abnormal growth plate development in NOMID mice.
PMID- 28687791
TI - Spectral Tuning Mechanism of Primate Blue-sensitive Visual Pigment Elucidated by
FTIR Spectroscopy.
AB - Protein-bound water molecules are essential for the structure and function of
many membrane proteins, including G-protein-coupled receptors (GPCRs). Our prior
work focused on studying the primate green- (MG) and red- (MR) sensitive visual
pigments using low-temperature Fourier transform infrared (FTIR) spectroscopy,
which revealed protein-bound waters in both visual pigments. Although the
internal waters are located in the vicinity of both the retinal Schiff base and
retinal beta-ionone ring, only the latter showed differences between MG and MR,
which suggests their role in color tuning. Here, we report FTIR spectra of
primate blue-sensitive pigment (MB) in the entire mid-IR region, which reveal the
presence of internal waters that possess unique water vibrational signals that
are reminiscent of a water cluster. These vibrational signals of the waters are
influenced by mutations at position Glu113 and Trp265 in Rh, which suggest that
these waters are situated between these two residues. Because Tyr265 is the key
residue for achieving the spectral blue-shift in lambdamax of MB, we propose that
these waters are responsible for the increase in polarity toward the retinal
Schiff base, which leads to the localization of the positive charge in the Schiff
base and consequently causes the blue-shift of lambdamax.
PMID- 28687792
TI - MALDI-TOF MS as a Novel Tool for the Estimation of Postmortem Interval in Liver
Tissue Samples.
AB - Estimation of the postmortem interval (PMI) is a complicated task in forensic
medicine, especially during homicide and unwitnessed death investigations. Many
biological, chemical, and physical indicators can be used to determine the
postmortem interval, but most are not accurate. Here, we present a novel matrix
assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF
MS) method that can be used for the estimation of PMI using molecular images and
multivariate analyses. In this study, we demonstrate that both rat and human
liver tissues of various PMIs (0, 2, 4, and 6days) can be discriminated using
MALDI imaging and principal component analysis (PCA). Using genetic algorithm
(GA), supervised neural network (SNN), and quick classifier (QC) methods, we
built 6 classification models, which showed high recognition capability and good
cross-validation. The histological changes in all the samples at different time
points were also consistent with the changes seen in MALDI imaging. Our work
suggests that MALDI-TOF MS, along with multivariate analysis, can be used to
determine intermediate PMIs.
PMID- 28687793
TI - The effect of tetrahedron framed permeable weirs on river bed stability in a
mountainous area under clear water conditions.
AB - A flexible riverbed protection called tetrahedron framed permeable weirs (TFPW)
is proposed to protect riverbeds in mountainous areas from scouring. Under clear
water conditions, a series of laboratory flume experiments were performed to
study the effects of TFPW with different layout types on the stability of
riverbeds. The objectives of this paper were to advance understanding of the role
that TFPW play in the erosion process of river beds and to optimize the TFPW
design for reducing velocity, promoting sediment deposition and good structural
stability. Data on velocity distribution and variation, equilibrium bathymetry,
flow resistance, bed form characteristics and structural stability were collected
and analyzed. The results indicate that (1) with good structural stability, all
the TFPW with different layout types had significant effects on the stabilization
of the riverbed by reducing velocity, raising the water level, increasing the
roughness coefficient, protecting the riverbed from degradation and promoting
deposition; and (2) the random Double TFPW with large rates of deceleration,
large deposition ranges, and good structural stability, and the paved Single TFPW
with small rates of deceleration but large deposition ranges and perfect
structural stability, were suitable and optimal for riverbed protection in a
clear water channel.
PMID- 28687794
TI - Dynamic responses to silicon in Thalasiossira pseudonana - Identification,
characterisation and classification of signature genes and their corresponding
protein motifs.
AB - The diatom cell wall, or frustule, is a highly complex, three-dimensional
structure consisting of nanopatterned silica as well as proteins and other
organic components. While some key components have been identified, knowledge on
frustule biosynthesis is still fragmented. The model diatom Thalassiosira
pseudonana was subjected to silicon (Si) shift-up and shift-down situations.
Cellular and molecular signatures, dynamic changes and co-regulated clusters
representing the hallmarks of cellular and molecular responses to changing Si
availabilities were characterised. Ten new proteins with silaffin-like motifs,
two kinases and a novel family of putatively frustule-associated transmembrane
proteins induced by Si shift-up with a possible role in frustule biosynthesis
were identified. A separate cluster analysis performed on all significantly
regulated silaffin-like proteins (SFLPs), as well as silaffin-like motifs,
resulted in the classification of silaffins, cingulins and SFLPs into distinct
clusters. A majority of the genes in the Si-responsive clusters are highly
divergent, but positive selection does not seem to be the driver behind this
variability. This study provides a high-resolution map over transcriptional
responses to changes in Si availability in T. pseudonana. Hallmark Si-responsive
genes are identified, characteristic motifs and domains are classified, and
taxonomic and evolutionary implications outlined and discussed.
PMID- 28687795
TI - The Anti-Hiv Candidate Abx464 Dampens Intestinal Inflammation by Triggering Il-22
Production in Activated Macrophages.
AB - The progression of human immunodeficiency virus (HIV) is associated with mucosal
damage in the gastrointestinal (GI) tract. This damage enables bacterial
translocation from the gut and leads to subsequent inflammation. Dextran sulfate
sodium (DSS-exposure) is an established animal model for experimental colitis
that was recently shown to recapitulate the link between GI-tract damage and
pathogenic features of SIV infection. The current study tested the protective
properties of ABX464, a first-in-class anti-HIV drug candidate currently in phase
II clinical trials. ABX464 treatment strongly attenuated DSS-induced colitis in
mice and produced a long-term protection against prolonged DSS-exposure after
drug cessation. Consistently, ABX464 reduced the colonic production of the
inflammatory cytokines IL-6 and TNFalpha as well as that of the chemoattractant
MCP-1. However, RNA profiling analysis revealed the capacity of ABX464 to induce
the expression of IL-22, a cytokine involved in colitis tissue repair, both in
DSS-treated mice and in LPS-stimulated bone marrow-derived macrophages.
Importantly, anti-IL-22 antibodies significantly reduced the protective effect of
ABX464 on colitis in DSS-treated mice. Because reduced IL-22 production in the
gut mucosa is an established factor of HIV and DSS-induced immunopathogenesis,
our data suggest that the anti-inflammatory properties of ABX464 warrant
exploration in both HIV and inflammatory ulcerative colitis (UC) disease.
PMID- 28687796
TI - Long-range Stripe Nanodomains in Epitaxial (110) BiFeO3 Thin Films on (100)
NdGaO3 Substrate.
AB - Here, we report the observation of ferroelectric and ferroelastic nanodomains in
(110)-oriented BiFeO3 (BFO) thin films epitaxially grown on low symmetric (100)
NdGaO3 (NGO) substrate. We observed long range ordering of ferroelectric 109
degrees stripe nanodomains separated by periodic vertical domain walls in as
grown 130 nm thick BFO films. The effect of La0.67Sr0.33CoO3 (LSCO) conducting
interlayer on domain configurations in BFO/NGO film was also observed with
relatively short range-ordering of stripe domains due to the modified
electrostatic boundary conditions in BFO/LSCO/NGO film. Additional studies on B
site doping of Nb ions in BFO films showed change in the domain structures due to
doping induced change in lattice anisotropy while maintaining the stripe domain
morphology with 109 degrees domain wall. This long-range array of ferroelectric
and ferroelastic domains can be useful for optoelectronic devices and
ferroelastic templates for strain coupled artificial magnetoelectric
heterostructures.
PMID- 28687797
TI - Operating Nanobeams in a Quantum Fluid.
AB - Microelectromechanical (MEMS) and nanoelectromechanical systems (NEMS) are ideal
candidates for exploring quantum fluids, since they can be manufactured
reproducibly, cover the frequency range from hundreds of kilohertz up to
gigahertz and usually have very low power dissipation. Their small size offers
the possibility of probing the superfluid on scales comparable to, and below, the
coherence length. That said, there have been hitherto no successful measurements
of NEMS resonators in the liquid phases of helium. Here we report the operation
of doubly-clamped aluminium nanobeams in superfluid 4He at temperatures spanning
the superfluid transition. The devices are shown to be very sensitive detectors
of the superfluid density and the normal fluid damping. However, a further and
very important outcome of this work is the knowledge that now we have
demonstrated that these devices can be successfully operated in superfluid 4He,
it is straightforward to apply them in superfluid 3He which can be routinely
cooled to below 100 MUK. This brings us into the regime where nanomechanical
devices operating at a few MHz frequencies may enter their mechanical quantum
ground state.
PMID- 28687798
TI - Achieving low-emissivity materials with high transmission for broadband radio
frequency signals.
AB - The use of low-emissivity (low-e) materials in modern buildings is an extremely
efficient way to save energy. However, such materials are coated by metallic
films, which can strongly block radio-frequency signals and prevent indoor
outdoor wireless communication. Here, we demonstrate that, when specially
designed metallic metasurfaces are covered on them, the low-e materials can
remain low emissivity for thermal radiation and allow very high transmission for
a broad band of radio-frequency signals. It is found that the application of air
connected metasurfaces with subwavelength periods is critical to the observed
high transmission. Such effects disappear if periods are comparable to
wavelengths or metal-connected structures are utilized. The conclusion is
supported by both simulations and experiments. Advantages such as easy to
process, low cost, large-area fabrication and design versatility of the
metasurface make it a promising candidate to solve the indoor outdoor
communication problem.
PMID- 28687799
TI - The chromosomes and the mitogenome of Ceratitis fasciventris (Diptera:
Tephritidae): two genetic approaches towards the Ceratitis FAR species complex
resolution.
AB - Ceratitis fasciventris is a serious agricultural pest of the Tephritidae family
that belongs to the African Ceratitis FAR species complex. Species limits within
the FAR complex are obscure and multidisciplinary approaches have attempted to
resolve phylogenetic relationships among its members. These studies support the
existence of at least three additional species in the complex, C. anonnae, C.
rosa and C. quilicii, while they indicate the presence of two structured
populations (F1 and F2) within the C. fasciventris species. In the present study
we present the mitotic karyotype, polytene chromosome maps, in situ hybridization
data and the complete mitochondrial genome sequence of an F2 population of C.
fasciventris. This is the first polytene chromosome map and complete mitogenome
of a member of the FAR complex and only the second reported for the Ceratitis
genus. Both polytene chromosomes and mitochondrial sequence could provide
valuable information and be used as reference for comparative analysis among the
members of the complex towards the clarification of their phylogenetic
relationships.
PMID- 28687800
TI - PKCalpha-mediated phosphorylation of LSD1 is required for presynaptic plasticity
and hippocampal learning and memory.
AB - Lysine-specific demethylase 1 (LSD1) is a histone demethylase that participates
in transcriptional repression or activation. Recent studies reported that LSD1 is
involved in learning and memory. Although LSD1 phosphorylation by PKCalpha was
implicated in circadian rhythmicity, the importance of LSD1 phosphorylation in
learning and memory is unknown. In this study, we examined the roles of LSD1 in
synaptic plasticity and memory using Lsd1 SA/SA knock-in (KI) mice, in which a
PKCalpha phosphorylation site is mutated. Interestingly, short-term and long-term
contextual fear memory as well as spatial memory were impaired in Lsd1 KI mice.
In addition, short-term synaptic plasticity, such as paired pulse ratio and post
tetanic potentiation was impaired, whereas long-term synaptic plasticity,
including long-term potentiation and long-term depression, was normal. Moreover,
the frequency of miniature excitatory postsynaptic current was significantly
increased, suggesting presynaptic dysfunction in Lsd1 KI mice. Consistent with
this, RNA-seq analysis using the hippocampus of Lsd1 KI mice showed significant
alterations in the expressions of presynaptic function-related genes.
Intriguingly, LSD1n-SA mutant showed diminished binding to histone deacetylase 1
(HDAC1) compared to LSD1n-WT in SH-SY5Y cells. These results suggest that LSD1 is
involved in the regulation of presynaptic gene expression and subsequently
regulates the hippocampus-dependent memory in phosphorylation-dependent manner.
PMID- 28687801
TI - Altered KYN/TRP, Gln/Glu, and Met/methionine sulfoxide ratios in the blood plasma
of medication-free patients with major depressive disorder.
AB - Capillary electrophoresis-time-of-flight mass spectrometry (CE-TOFMS) is a
comprehensive, quantitative, and high throughput tool used to analyze metabolite
profiles. In the present study, we used CE-TOFMS to profile metabolites found in
the blood plasma of 33 medication-free patients with major depressive disorder
(MDD) and 33 non-psychiatric control subjects. We then investigated changes which
occurred in the metabolite levels during an 8-week treatment period. The
medication-free MDD patients and control subjects showed significant differences
in their mean levels of 33 metabolites, including kynurenine (KYN), glutamate
(Glu), glutamine (Gln), methionine sulfoxide, and methionine (Met). In
particular, the ratios of KYN to tryptophan (TRP), Gln to Glu, and Met to
methionine sulfoxide were all significantly different between the two groups.
Among the 33 metabolites with altered levels in MDD patients, the levels of KYN
and Gln, as well as the ratio of Gln to Glu, were significantly normalized after
treatment. Our findings suggest that imbalances in specific metabolite levels may
be involved in the pathogenesis of MDD, and provide insight into the mechanisms
by which antidepressant agents work in MDD patients.
PMID- 28687802
TI - Rice Flowering Locus T 1 plays an important role in heading date influencing
yield traits in rice.
AB - Important role of flowering genes in enhancing grain productivity in rice has
become well recognized for a number of key genes regulating the florigen
production, but little has been known for the two florigen genes themselves. In
this study, pleiotropism of Rice Flowering Locus T 1 (RFT1), one of the two
florigen genes in rice, was firstly evaluated using near isogenic lines (NILs)
carrying RFT1 alleles from the indica rice cultivars Zhenshan 97 (ZS97) and
Milyang 46, respectively, and then determined by transformation of the RFT1 ZS97
allele into a japonica rice variety, Zhonghua 11. The RFT1 ZS97 allele was shown
to delay heading and increase plant height, grain weight, grain number and grain
yield, indicating that RFT1 plays an important role in the growth and development
of rice. This study has also validated the potential of using a new type of
genetic resource, sequential residual heterozygotes (SeqRHs), for QTL fine
mapping. A step-by-step approach was employed for SeqRHs identification, NIL
development and QTL fine-mapping. The heterozygous segments and candidate QTL
regions were gradually narrowed down. Eventually, the QTL region was delimited to
a 1.7 kb region containing a single gene.
PMID- 28687803
TI - Self-powered ZnS Nanotubes/Ag Nanowires MSM UV Photodetector with High On/Off
Ratio and Fast Response Speed.
AB - In this study, we design and demonstrate a novel type of self-powered UV
photodetectors (PDs) using single-crystalline ZnS nanotubes (NTs) as the
photodetecting layer and Ag nanowires (NWs) network as transparent electrodes.
The self-powered UV PDs with asymmetric metal-semiconductor-metal (MSM) structure
exhibit attractive photovoltaic characteristic at 0 V bias. Device performance
analysis reveals that the as-assembled PDs have a high on/off ratio of 19173 and
a fast response speed (taur = 0.09 s, tauf = 0.07 s) without any external bias.
These values are even higher than that of ZnS nanostructures- and ZnS
heterostructure-based PDs at a large bias voltage. Besides, its UV sensivity,
responsivity and detectivity at self-powered mode can reach as high as 19172,
2.56 A/W and 1.67 * 1010 cm Hz1/2 W-1, respectively. In addition, the
photosensing performance of the self-powered UV PDs is studied in different
ambient conditions (e.g., in air and vacuum). Moreover, a physical model based on
band energy theory is proposed to explain the origin of the self-driven
photoresponse characteristic in our device. The totality of the above study
signifies that the present self-powered ZnS NTs-based UV nano-photodetector may
have promising application in future self-powered optoelectronic devices and
integrated systems.
PMID- 28687805
TI - Nuclear Physics Meets the Sources of the Ultra-High Energy Cosmic Rays.
AB - The determination of the injection composition of cosmic ray nuclei within
astrophysical sources requires sufficiently accurate descriptions of the source
physics and the propagation - apart from controlling astrophysical uncertainties.
We therefore study the implications of nuclear data and models for cosmic ray
astrophysics, which involves the photo-disintegration of nuclei up to iron in
astrophysical environments. We demonstrate that the impact of nuclear model
uncertainties is potentially larger in environments with non-thermal radiation
fields than in the cosmic microwave background. We also study the impact of
nuclear models on the nuclear cascade in a gamma-ray burst radiation field,
simulated at a level of complexity comparable to the most precise cosmic ray
propagation code. We conclude with an isotope chart describing which information
is in principle necessary to describe nuclear interactions in cosmic ray sources
and propagation.
PMID- 28687804
TI - On the effects of multimodal information integration in multitasking.
AB - There have recently been considerable advances in our understanding of the
neuronal mechanisms underlying multitasking, but the role of multimodal
integration for this faculty has remained rather unclear. We examined this issue
by comparing different modality combinations in a multitasking (stop-change)
paradigm. In-depth neurophysiological analyses of event-related potentials (ERPs)
were conducted to complement the obtained behavioral data. Specifically, we
applied signal decomposition using second order blind identification (SOBI) to
the multi-subject ERP data and source localization. We found that both general
multimodal information integration and modality-specific aspects (potentially
related to task difficulty) modulate behavioral performance and associated
neurophysiological correlates. Simultaneous multimodal input generally increased
early attentional processing of visual stimuli (i.e. P1 and N1 amplitudes) as
well as measures of cognitive effort and conflict (i.e. central P3 amplitudes).
Yet, tactile-visual input caused larger impairments in multitasking than audio
visual input. General aspects of multimodal information integration modulated the
activity in the premotor cortex (BA 6) as well as different visual association
areas concerned with the integration of visual information with input from other
modalities (BA 19, BA 21, BA 37). On top of this, differences in the specific
combination of modalities also affected performance and measures of
conflict/effort originating in prefrontal regions (BA 6).
PMID- 28687806
TI - Morphology Control of Energy-Gap-Engineered Nb2O5 Nanowires and the
Regioselective Growth of CdS for Efficient Carrier Transfer Across an Oxide
Sulphide Nanointerface.
AB - Semiconductor nanowires with both nano- and micrometre dimensions have been used
as effective materials for artificial photosynthesis; however, a single synthesis
approach to provide rational control over the macroscopic morphology, which can
allow for the high-throughput screening of photocatalytic performance, and
carrier transfer between oxide and sulphide nanostructures has been poorly known.
Our recent findings indicate that a single parameter, Nb foil thickness, in a
vapor-phase synthesis method can alter the macroscopic morphology of resulting
Nb2O5 nanowires. Thick Nb foil results in a free-standing Nb2O5 film, whereas a
thinner foil leads to fragmentation to give a powder. During the synthesis
process, a Rh dopant was provided through metal-organic chemical vapor deposition
to reduce the Nb2O5 energy gap. Upon irradiation with visible light (lambda > 440
nm), the free-standing nanowire film [Nb2O5:Rh-NW(F)] showed photoanodic current
with a Faradaic efficiency of 99% for O2 evolution. Under identical irradiation
conditions, the powdered counterpart [Nb2O5:Rh-NW(P)] showed activity for O2
evolution in the presence of an electron acceptor. The poor water-reduction
ability was greatly enhanced by the Au-catalysed vapor-liquid-solid (VLS) growth
of H2-evolving CdS onto the reduction sites of Nb2O5:Rh-NW(P) [Au/CdS/Nb2O5:Rh
NW(P)].
PMID- 28687807
TI - Efficient activation of the lymphangiogenic growth factor VEGF-C requires the C
terminal domain of VEGF-C and the N-terminal domain of CCBE1.
AB - The collagen- and calcium-binding EGF domains 1 (CCBE1) protein is necessary for
lymphangiogenesis. Its C-terminal collagen-like domain was shown to be required
for the activation of the major lymphangiogenic growth factor VEGF-C (Vascular
Endothelial Growth Factor-C) along with the ADAMTS3 (A Disintegrin And
Metalloproteinase with Thrombospondin Motifs-3) protease. However, it remained
unclear how the N-terminal domain of CCBE1 contributed to lymphangiogenic
signaling. Here, we show that efficient activation of VEGF-C requires its C
terminal domain both in vitro and in a transgenic mouse model. The N-terminal EGF
like domain of CCBE1 increased VEGFR-3 signaling by colocalizing pro-VEGF-C with
its activating protease to the lymphatic endothelial cell surface. When the
ADAMTS3 amounts were limited, proteolytic activation of pro-VEGF-C was supported
by the N-terminal domain of CCBE1, but not by its C-terminal domain. A single
amino acid substitution in ADAMTS3, identified from a lymphedema patient, was
associated with abnormal CCBE1 localization. These results show that CCBE1
promotes VEGFR-3 signaling and lymphangiogenesis by different mechanisms, which
are mediated independently by the two domains of CCBE1: by enhancing the cleavage
activity of ADAMTS3 and by facilitating the colocalization of VEGF-C and ADAMTS3.
These new insights should be valuable in developing new strategies to
therapeutically target VEGF-C/VEGFR-3-induced lymphangiogenesis.
PMID- 28687808
TI - Predictors of Development and Progression of Retinopathy in Patients with Type 2
Diabetes: Importance of Blood Pressure Parameters.
AB - Diabetic retinopathy (DR) is a chronic microvascular complication associated a
worse prognosis. We aimed to evaluate the predictors of development/progression
of DR in a cohort of 544 high-risk patients with type 2 diabetes who had annual
ophthalmologic examinations over a median follow-up of 6 years. Ambulatory blood
pressure (BP) monitoring and aortic stiffness by carotid-femoral pulse wave
velocity were performed. Multivariate Cox survival analysis examined the
independent predictors of development or progression of DR. During follow-up, 156
patients either newly-developed or worsened DR. Patients who developed/progressed
DR had longer diabetes duration, higher ambulatory and clinic BP levels, higher
aortic stiffness, and poorer glycemic control than patients who did not
developed/progressed DR. After adjustments for baseline retinopathy prevalence,
age and sex, a longer diabetes duration (p < 0.001), higher baseline ambulatory
BPs (p = 0.013, for 24-hour diastolic BP), and higher mean cumulative exposure of
HbA1c (p < 0.001), clinic diastolic BP (p < 0.001) and LDL-cholesterol (p = 0.05)
during follow-up were the independent predictors of development/progression of
DR. BP parameters were only predictors of DR development. In conclusion, a longer
diabetes duration, poorer glycemic and lipid control, and higher BPs were the
main predictors of development/progression of DR. Mean cumulative clinic
diastolic BP was the strongest BP-related predictor.
PMID- 28687809
TI - Genetic variants of TRAF6 modulate peritoneal immunity and the risk of
spontaneous bacterial peritonitis in cirrhosis: A combined prospective
retrospective study.
AB - Alterations of the innate immunity contribute to the development of spontaneous
bacterial peritonitis (SBP) in liver cirrhosis. Given its role in immune
signaling, antimicrobial function, and macrophage differentiation, we
hypothesized that genetic polymorphisms of TRAF6 modulate the risk of SBP. Thus,
we determined theTRAF6 haplotype in 432 patients with cirrhosis and ascites using
the haplotype-tagging single nucleotide polymorphisms rs331457 and rs5030419. In
addition, peritoneal macrophages were immunomagnetically isolated and
characterized. Overall, 122 (28%) patients had an episode of SBP. In the combined
prospective-retrospective analysis the frequency of SBP differed between the four
haplotypes (P = 0.014) and was the highest in 102 patients carrying the rs331457
but not the rs5030419 variant, when compared to other haplotypes (odds ratio 1.95
[1.22-3.12]) or to the wild-type (odds ratio 1.71 [1.04-2.82]). This association
was confirmed in multivariate logistic regression (adjusted odds ratio 2.00 [1.24
3.22]) and in prospective sensitivity analysis (hazard ratio 2.09 [1.08-4.07]; P
= 0.03). The risk haplotype was associated with lower concentrations of the
immune activation marker soluble CD87 in ascitic fluid and with a decreased
expression of IL-6 and CXCL8 in isolated peritoneal macrophages. In conclusion,
genetic polymorphisms of TRAF6 are associated with decreased peritoneal immune
activation and an increased risk of SBP.
PMID- 28687810
TI - Full left ventricular coverage is essential for the accurate quantification of
the area-at-risk by T1 and T2 mapping.
AB - T2-weighted cardiovascular magnetic resonance (CMR) using a 3-slice approach has
been shown to accurately quantify the edema-based area-at-risk (AAR) in ST
segment elevation myocardial infarction (STEMI). We aimed to compare the
performance of a 3-slice approach to full left ventricular (LV) coverage for the
AAR by T1 and T2 mapping and MI size. Forty-eight STEMI patients were
prospectively recruited and underwent a CMR at 4 +/- 2 days. There was no
difference between the AARfull LV and AAR3-slices by T1 (P = 0.054) and T2
mapping (P = 0.092), with good correlations but small biases and wide limits of
agreements (T1-mapping: N = 30, R2 = 0.85, bias = 1.7 +/- 9.4% LV; T2-mapping: N
= 48, R2 = 0.75, bias = 1.7 +/- 12.9% LV). There was also no significant
difference between MI size3-slices and MI sizefull LV (P = 0.93) with an
excellent correlation between the two (R2 0.92) but a small bias of 0.5% and a
wide limit of agreement of +/-7.7%. Although MSI was similar between the 2
approaches, MSI3-slices performed poorly when MSI was <0.50. Furthermore, using
AAR3-slices and MI sizefull LV resulted in 'negative' MSI in 7/48 patients. Full
LV coverage T1 and T2 mapping are more accurate than a 3-slice approach for
delineating the AAR, especially in those with MSI < 0.50 and we would advocate
full LV coverage in future studies.
PMID- 28687811
TI - Electronically Switchable Broadband Metamaterial Absorber.
AB - In this study, the novel electronically switchable broadband metamaterial
absorber, using a PIN diode, is proposed. The unit cell of the absorber was
designed with a Jerusalem-cross resonator and an additive ring structure, based
on the FR-4 dielectric substrate. Chip resistors and PIN diodes were used to
provide both a broadband characteristic and a switching capability. To satisfy
the polarization insensitivity, the unit cell was designed as a symmetrical
structure, including the DC bias network, electronic devices, and conductor
patterns. The performance of the proposed absorber was verified using full-wave
simulation and measurements. When the PIN diode was in the ON state, the proposed
absorber had a 90% absorption bandwidth from 8.45-9.3 GHz. Moreover, when the PIN
diode was in the OFF state, the 90% absorption bandwidth was 9.2-10.45 GHz.
Therefore, the absorption band was successfully switched between the low
frequency band and the high-frequency band as the PIN diode was switched between
the ON and OFF states. Furthermore, the unit cell of the proposed absorber was
designed as a symmetrical structure, and its performance showed insensitivity
with respect to the polarization angle.
PMID- 28687814
TI - The persistence of intracellular Staphylococcus aureus in the sinuses: a
longitudinal study.
AB - BACKGROUND: Staphylococcus aureus (S. aureus) can reside within the sinonasal
mucosa in chronic rhinosinusitis patients and causes recurrent infections. Within
the host cell, S. aureus can evade host immune detection enabling its own
survival. We hypothesise that S. aureus can persist within the sinonasal
epithelium for a prolonged period without immune activation. METHODOLOGY:
Patients with chronic rhinosinusitis with nasal polyps (CRSwNP) undergoing two
sinus surgeries were included. Immunohistochemistry and Haematoxylin and Eosin
stains were used to determine intracellular S. aureus (ICSA) status and
inflammatory cell count, respectively. One-way ANOVA and paired t-tests were
performed for comparison between ICSA subgroups and within each subgroup,
respectively. RESULTS: Histopathological specimens from 34 patients (68
procedures) were included. ICSA positivity (ICSA+) was seen in 43 specimens
(63.2%) from 26 (76%) patients. 18 (52.9%) of those were ICSA+ in both operations
while 8 (23.5%) patients were ICSA+ in only one of the operations. 8 (23.5%)
patients were ICSA negative in both operations. There was no difference in the
number of eosinophils, lymphocyte and neutrophils between ICSA subgroups.
CONCLUSIONS: This study demonstrated that S. aureus is found intracellularly
within CRSwNP tissue at multiple time points without an increase in the number of
eosinophils, lymphocytes and neutrophils. This finding supports our hypothesis
that ICSA is able to escape from host detection and resides within the sinonasal
mucosa despite intense treatment.
PMID- 28687813
TI - Cancer risk factors among people living with HIV/AIDS in China: a systematic
review and meta-analysis.
AB - Cancer is a leading cause of death among people living with HIV/AIDS (PLWHA). We
conducted a systematic review and meta-analysis to evaluate prevalence of cancer
risk factors among Chinese PLWHA based on 102 articles. Random effects meta
analysis was used to calculate the summary prevalence estimate (sPrev) and 95%
confidence interval (CI) for each cancer risk factor by demographic group.
Overall, the sPrev for each risk factor among Chinese PLWHA was: 41.1% (95% CI:
35.3-46.9%) for current smoking; 30.3% (95% CI: 23.3-37.4%) for current alcohol
consumption; 24.4% (95% CI: 14.7-30.2%) for overweight and obesity; 12.5% (95%
CI: 10.6-14.3%) for hepatitis B virus infection; 29.1% (95% CI: 23.6-34.5%) for
hepatitis C virus infection; 33.9% (95% CI: 24.3-43.5%) for high-risk human
papillomavirus infection from cervical samples and 78.6% (95% CI: 69.4-87.7%)
from anal samples; 2.7% (95% CI: 0.7-4.7%) for Epstein-Barr virus (EBV)
immunoglobulin M (IgM) positivity, 94.7% (95% CI: 90.7-98.8%) for EBV IgG
positivity and 25.6% (95% CI: 12.4-38.8%) for EBV DNA positivity; 14.9% (95% CI:
12.4-17.4%) for human herpes virus 8 infection. The prevalence of major cancer
risk factors was high among PLWHA in China, suggesting an urgent need for
interventions to reduce cancer risk in this high-risk group.
PMID- 28687812
TI - Blast-Induced Tinnitus and Elevated Central Auditory and Limbic Activity in Rats:
A Manganese-Enhanced MRI and Behavioral Study.
AB - Blast-induced tinitus is the number one service-connected disability that
currently affects military personnel and veterans. To elucidate its underlying
mechanisms, we subjected 13 Sprague Dawley adult rats to unilateral 14 psi blast
exposure to induce tinnitus and measured auditory and limbic brain activity using
manganese-enhanced MRI (MEMRI). Tinnitus was evaluated with a gap detection
acoustic startle reflex paradigm, while hearing status was assessed with prepulse
inhibition (PPI) and auditory brainstem responses ( ABR s). Both anxiety and
cognitive functioning were assessed using elevated plus maze and Morris water
maze, respectively. Five weeks after blast exposure, 8 of the 13 blasted rats
exhibited chronic tinnitus. While acoustic PPI remained intact and ABR thresholds
recovered, the ABR wave P1-N1 amplitude reduction persisted in all blast-exposed
rats. No differences in spatial cognition were observed, but blasted rats as a
whole exhibited increased anxiety. MEMRI data revealed a bilateral increase in
activity along the auditory pathway and in certain limbic regions of rats with
tinnitus compared to age-matched controls. Taken together, our data suggest that
while blast-induced tinnitus may play a role in auditory and limbic
hyperactivity, the non-auditory effects of blast and potential traumatic brain
injury may also exert an effect.
PMID- 28687815
TI - Postoperative long-term morbidity of extended endoscopic maxillectomy for
inverted papilloma.
AB - BACKGROUND: Extended endoscopic maxillectomy (Sturmann-Canfield procedure) allows
full visualization of the maxillary sinus by sectioning the lacrimal duct and
removing the medial part of the anterior maxillary wall. The aim of this study is
to evaluate the morbidity of Sturmann-Canfield procedure in patients treated for
inverted papilloma. METHODOLOGY: The clinical records of all patients treated
with a Sturmann-Canfield procedure for inverted papilloma from October 2000 to
September 2015 at two teaching hospitals were reviewed. All patients were
evaluated by nasal endoscopy and lacrimal system patency was assessed. Pre
maxillary cutaneous sensitivity was tested with a Semmes-Weinstein aesthesiometer
and thermic stimulation. The SNOT-22 questionnaire was administered. Patients
were also asked to report any other post-surgical complaints. RESULTS: Fifty-nine
patients were identified. Mean follow-up after surgery was 66.3 months. Mean SNOT
22 score was 5.94 (range 0-20); the majority of patients (86%) had a SNOT-22
symptom score of 3 or lower. Mucocoele occurred in 3 (5%) cases. Lacrimal pathway
obstruction was observed in 7 (12%) patients. Fourteen (24%) patients complained
of paraesthesia in the malar area; hypoesthesia was present in only 5 (8%) cases.
Hypoesthesia in the region innervated by the anterior superior alveolar nerve was
detected in 17 (29%) patients. One patient reported a slight depression of
paralateronasal soft tissues. CONCLUSIONS: Although nasal function outcomes and
the results from SNOT-22 questionnaires were favourable, a high rate of
neurologic and lacrimal complications was observed. Potential morbidity of the
intervention, including the possibility of negative aesthetic sequelae, should be
discussed during preoperative counselling.
PMID- 28687816
TI - Marshaling FDA Benefit-Risk Expertise to Address the Current Opioid Abuse
Epidemic.
PMID- 28687818
TI - Addressing the Challenges for Otolaryngology Research to Inform Patient Care and
Outcomes.
PMID- 28687819
TI - Association of Lateral Crural Overlay Technique With Strength of the Lower
Lateral Cartilages.
AB - Importance: The lateral crural overlay technique is a powerful technique for
altering nasal tip projection and rotation. By overlapping and thus shortening
the lateral crura, the nasal tip is shortened and rotated upward, thus decreasing
projection and increasing rotation. There is no data to show the association of
this technique with the strength of the lower lateral cartilage. Strengthening of
the lower lateral cartilages would presumably lead to resistance to external
nasal valve collapse and improved airway. Objective: In this cadaver study, we
set out to determine the differences in the strength and resilience of the
lateral crura after performing lateral crural overlay using 2 different
techniques. Design, Setting, and Participants: Seven individual lower lateral
cartilages were harvested from 6 cadavers for analysis. Each of the 7 cartilages
was included sequentially in 3 test groups in the following order: a preprocedure
group (preP), a postprocedure group (postP) in which the lateral crural overlay
technique was performed, and a postprocedure with glue group (postPG) in which
cyanoacrylate glue was added to the postP cartilages to simulate cartilage
healing. A force gauge was used to measure the force required to deflect the
lower lateral cartilages distances from 1 to 6 mm. Main Outcomes and Measures:
Differences measured in newtons (N) for strength and resilience of lateral crura
between the preP, postP, and postPG groups. Results: A statistically significant
increase in lower lateral cartilage resilience was noted between the preP and
postPG groups at all distances of tip deflection (1 mm, 0.20 vs 0.70 N; P < .001;
2 mm, 0.26 vs 1.13 N; P < .001; 3 mm, 0.31 vs 1.53 N; P < .001; 4 mm, 0.41 vs
2.05 N; P < .001; 5 mm, 0.68 vs 2.60 N; P < .001; 6 mm, 1.49 vs 3.26 N; P = .03).
There was a statistically significant difference between the postP and postPG
groups in the amount of force required to deflect the cartilages 1 to 5 mm (1 mm,
0.24 vs 0.70 N; P < .001; 2 mm, 0.34 vs 1.13 N; P < .001; 3 mm, 0.51 vs 1.53 N; P
< .001; 4 mm, 0.77 vs 2.05 N; P < .001; 5 mm, 1.32 vs 2.60 N; P = .01), but not 6
mm (2.33 vs 3.26 N; P = .31). Conclusions and Relevance: The lateral crural
overlay technique affords increased strength and resilience to the lateral crura
of the lower lateral cartilages, which should in turn decrease the likelihood of
external nasal valve collapse postoperatively. Level of Evidence: NA.
PMID- 28687817
TI - Etiologic and Audiologic Characteristics of Patients With Pediatric-Onset
Unilateral and Asymmetric Sensorineural Hearing Loss.
AB - Importance: Pediatric-onset unilateral and asymmetric sensorineural hearing loss
(SNHL) is a common condition, but in most patients, the cause remains unclear;
thus, determination of the hearing outlook is difficult. Objective: To analyze
the etiologic and audiologic characteristics of pediatric-onset unilateral and
asymmetric SNHL. Design, Setting, and Participants: In this retrospective cohort
study performed from January 1, 2008, through December 31, 2016, patients at a
tertiary referral center who were diagnosed with pediatric-onset unilateral or
asymmetric SNHL were divided into 3 groups according to their hearing levels:
unilateral hearing loss with scaled-out levels (UHL-SO), unilateral hearing loss
with residual hearing (UHL-RH), and asymmetric hearing loss (AHL). Main Outcomes
and Measures: Basic demographic data, family and medical histories, audiologic
results, imaging findings, and genetic results were ascertained and compared
among patients of the 3 groups. Results: A total of 133 patients (mean [SD] age,
9.1 [10.9] years; 63 [47.4%] male and 70 [52.6%] female), including 50 with UHL
SO, 42 with UHL-RH, and 41 with AHL, were enrolled for analyses. Of 50 patients
with UHL-SO, 49 (98.0%) had stable hearing levels with time, whereas 10 of 42
patients with UHL-RH (23.8%) and 18 of 41 patients with AHL (43.9%) revealed
progressive or fluctuating hearing loss. Inner ear malformations detected with
temporal bone high-resolution computed tomography, particularly cochlear aperture
stenosis, were detected at higher rates in patients with UHL-SO (9 of 31 [29.0%])
and UHL-RH (6 of 24 [25.0%]) than in those with AHL (1 of 30 [3.3%]). In
contrast, screening for mutations in 3 common deafness genes-GJB2, SLC26A4, and
MTRNR1-achieved definite diagnosis in a higher percentage of patients with AHL
(10 of 37 [27.0%]) than patients with UHL-SO (0 of 33) and UHL-RH (1 of 25
[4.0%]). Conclusions and Relevance: The UHL-SO and UHL-RH conditions share a
common or similar etiopathogenesis different from that of AHL. Imaging studies
and genetic testing might be prioritized during the respective general etiologic
workups for patients with UHL and AHL. Regular hearing checkups are warranted for
patients with UHL and AHL because a certain proportion of patients might sustain
progression in SNHL.
PMID- 28687820
TI - Mutation Frequencies in Patients With Early-Onset Colorectal Cancer-Reply.
PMID- 28687821
TI - Computer-aided detection and quantification of endolymphatic hydrops within the
mouse cochlea in vivo using optical coherence tomography.
AB - Diseases that cause hearing loss and/or vertigo in humans such as Meniere's
disease are often studied using animal models. The volume of endolymph within the
inner ear varies with these diseases. Here, we used a mouse model of increased
endolymph volume, endolymphatic hydrops, to develop a computer-aided objective
approach to measure endolymph volume from images collected 0.1). PPS period increased with
the square root of the distance to the canal (P < 0.0001). Conclusions: Small,
uniform crimp periods within the sheep LC and immediately adjacent PPS may
indicate that these tissues are setup to prevent large or heterogeneous
deformations that insult the neural tissues within the canal. An increasing more
variable period with distance from the canal provides a smooth transition of
mechanical properties that minimizes stress and strain concentrations.
PMID- 28687852
TI - Optical Coherence Tomographic Imaging of Posterior Episclera and Tenon's Capsule.
AB - Purpose: To investigate structural features of the posterior episclera and
Tenon's capsule in patients with high myopia. Methods: This hospital-based
observational study included highly myopic eyes (myopic refractive error > -8
diopters or axial length >=26.5 mm) in which the posterior sclera in its full
thickness could be visualized on swept-source optical coherence tomography (OCT)
images in all 12 radial scans centered on the fovea. We assessed the posterior
episclera and Tenon's capsule. Results: The study included 278 eyes of 175
patients (mean age, 60.9 +/- 11.4 years; range, 32-89 years; axial length, 30.7
+/- 1.9 mm; range, 26.5-36.6 mm). The episclera was detected outside of the
sclera in 164 eyes (59.0%) and appeared as a relatively uniform structure with a
reflectivity slightly lower than scleral reflectivity. In these eyes, mean
scleral thickness was 197 +/- 73 MUm in the foveal region and 164 +/- 64 MUm and
146 +/- 59 MUm at 1000 and 2500 MUm temporal to the fovea, respectively. The
posterior episclera was visualized in the region temporal to the fovea. Mean
episcleral thickness detected in 77 eyes was 80 +/- 27 MUm and 82 +/- 30 MUm at
1000 MUm and 2500 MUm temporal to the fovea, respectively. Tenon's capsule was
detected in 11 of the 278 eyes (4.0%) as structurally, loosely connected tissue
with a meshwork-like appearance. The measured thickness in four eyes was 60 +/-
32 MUm. In 25 eyes with extremely thin sclera (<100 MUm at 1000 MUm temporal to
the foveola), the mean thickness of the sclera and episclera were 87 +/- 11 MUm
and 65 +/- 15 MUm, respectively. Conclusions: Swept-source OCT applied to a
subset of highly myopic eyes with significant thinning of the retina and choroid
allowed visualization of the posterior sclera and episclera, and in some cases,
also Tenon's capsule.
PMID- 28687853
TI - Alterations to the Foveal Cone Mosaic of Diabetic Patients.
AB - Purpose: We measured localized changes occurring in the foveal cone
photoreceptors and related defects in the cone mosaic to alterations in the
nearby retinal vasculature. Methods: The central 4 degrees of the retina of 54
diabetic (53.7 +/- 12.5 years) and 85 control (35.8 +/- 15.2 years) participants
were imaged with the Indiana adaptive optics scanning laser ophthalmoscope.
Foveal cones and overlying retinal capillaries were imaged and infrared scanning
laser ophthalmoscopy (IR SLO) images and optical coherence tomography (OCT) B
scans were obtained. Follow-up imaging sessions were performed with intervals
from 4 to 50 months for 22 of the 54 diabetic participants. Results: The foveal
cone mosaics of 49 of 54 diabetic participants were of sufficient quality to
assess the absence or presence of small localized defects in the cone mosaic. In
13 of these 49 diabetic participants we found localized defects, visualized as
sharp-edged areas of cones with diminished reflectivity. These small, localized
areas ranged in size from 10 * 10 MUm to 75 * 30 MUm. Of these 13 participants
with cone defects, 11 were imaged over periods from 4 to 50 months and the
defects remained relatively stable. These dark regions were not shadows of
overlying retinal vessels, but all participants with these localized defects had
alterations in the juxtafoveal capillary network. Conclusions: The foveal cone
mosaic can show localized areas of dark cones that persist over time, that
apparently correspond to either missing or nonreflecting cones, and may be
related to local retinal ischemia.
PMID- 28687854
TI - Neuroprotective effects of vitamin D alone or in combination with lamotrigine
against lithium-pilocarpine model of status epilepticus in rats.
AB - Status epilepticus (SE) is considered one of the major serious forms of epilepsy
with high mortality rate. Since the currently available antiepileptic drugs have
low efficacy and high adverse effects, new more efficient and safe therapies are
critically needed. There is increasing evidence supporting dietary and
alternative therapies for epilepsy, including the ketogenic diet, modified Atkins
diet, and omega-3 fatty acids. Recent studies have shown significant prophylactic
and therapeutic potential of vitamin D (vit-D) use in many neurological
disorders. Therefore, in the present study, the neuroprotective effects and
mechanisms of vit-D alone or in combination with lamotrigine have been evaluated
in the lithium-pilocarpine model of SE in rats. Rats were divided into five
groups: normal group, SE group, lamotrigine (25 mg/kg/day) pretreated group, vit
D (1.5 mcg/kg/day) pretreated group, and group pretreated with vit-D and
lamotrigine for 2 weeks. At the end of treatment, SE was induced by single
intraperitoneal injection of LiCl (127 mg/kg), followed 24 h later by pilocarpine
(30 mg/kg). Seizures' latency, cognitive performance in Morris water maze, brain
oxidative stress biomarkers (glutathione, lipid peroxides, and nitric oxide),
brain neurochemistry (gamma-aminobutyric acid and glutamate), and brain
histopathology have been evaluated. Vit-D prevented pilocarpine-induced
behavioral impairments and oxidative stress in the brain; these results were
improved in combination with lamotrigine. Vit-D has a promising antiepileptic,
neuroprotective, and antioxidant effects. It can be provided to patients as a
supportive treatment besides antiepileptic drugs. However, clinical trials are
needed to establish its efficacy and safety.
PMID- 28687855
TI - Decreased spontaneous activity and altered evoked nociceptive response of rat
thalamic submedius neurons to lumbar vertebra thrust.
AB - The thalamus is a central structure important to modulating and processing all
mechanoreceptor input destined for the cortex. A large number of diverse
mechanoreceptor endings are stimulated when a high velocity low amplitude thrust
is delivered to the lumbar spine during spinal manipulation. The objective of
this study was to determine if a lumbar thrust alters spontaneous and/or evoked
nociceptive activity in medial thalamic submedius (Sm) neurons. Extracellular
recordings were obtained from 94 thalamic Sm neurons in 54 urethane-anesthetized
adult Wistar rats. Spontaneous activity was recorded 5 min before and after an L5
control (no thrust) and thrust (85% rat body weight; 100 ms) procedure. In a
subset of responsive nociceptive-specific neurons, mean changes in noxious-evoked
response (10-s pinch with clip; 795 g) at three sites (tail, contra- and
ipsilateral hindpaw) were determined following an L5 thrust. Mean changes in Sm
spontaneous activity (60 s bins) and evoked noxious response were compared using
a mixed model repeated measures ANOVA with Bonferroni post hoc t tests and paired
t tests, respectively. Compared to control, spontaneous Sm activity decreased 180
240 s following the lumbar thrust (p < 0.005). Inhibitory evoked responses were
attenuated in the contralateral hindpaw following an L5 thrust compared to
control (p < 0.05). No other changes in spontaneous or noxious-evoked Sm activity
were found. A delayed, but prolonged suppression of spontaneous Sm activity along
with changes in noxious-evoked inhibitory responses in the contralateral hindpaw
following lumbar vertebra thrust suggest that thalamic submedius neurons may play
a role in central pain modulation related to manual therapy intervention.
PMID- 28687856
TI - Professionals' preferences in prenatal counseling at the limits of viability: a
nationwide qualitative Dutch study.
AB - : Prenatal counseling practices at the limits of viability do vary, and
constructing a counseling framework based on guidelines, professional and
parental preferences, might achieve more homogeneity. We aimed to gain insight
into professionals' preferences on three domains of counseling, particularly
content, organization, and decision making and their influencing factors. A
qualitative, nationwide in-depth exploration among Dutch perinatal professionals
by semi-structured interviews in focus groups was performed. Regarding content of
prenatal counseling, preparing parents on the short-term situation (delivery room
care) and revealing their perspectives on "quality of life" were considered
important. Parents should be informed on the kind of decision, on the difficulty
of individual outcome predictions, on survival and mortality figures, short- and
long-term morbidity, and the burden of hospitalization. For organization, the
making of and compliance with agreements between professionals may promote joint
counseling by neonatologists and obstetricians. Supportive materials were
considered useful but only when up-to-date, in addition to the discussion and
with opportunity for personalization. Regarding decision making, it is not always
clear to parents that a prenatal decision needs to be made and they can
participate, influencing factors could be, e.g., unclear language, directive
counseling, overload of information, and an immediate delivery. There is limited
familiarity with shared decision making although it is the preferred model.
CONCLUSION: This study gained insight into preferred content, organization, and
decision making of prenatal counseling at the limits of viability and their
influencing factors from a professionals' perspective. What is Known: *
Heterogeneity in prenatal counseling at the limits of viability exists *
Differences between preferred counseling and actual practice also exists What is
New: * Insight into preferred content, organization, and decision making of
prenatal periviability counseling and its influencing factors from a
professionals' perspective. Results should be taken into account when performing
counseling. * Particularly the understanding of true shared decision making needs
to be improved. Furthermore, implementation of shared decision making in daily
practice needs more attention.
PMID- 28687857
TI - Improving catalytic performance of an arylacetonitrilase by semirational
engineering.
AB - Arylacetonitrilases have been widely acknowledged as important alternatives to
chemical catalysts for synthesizing optically pure 2-hydroxyphenylacetic acids
from nitriles. In this work, two residues (Thr132 and Ser190) located at the
catalytic tunnel in the active site of an arylacetonitrilase nitA from uncultured
organisms were mutated separately by site-directed mutagenesis. Ser190 was
demonstrated to be the critical position which has a greater influence on
arylacetonitrilase nitA activity than Thr132. The replacement of serine at
position 190 with glycine increases its activity toward mandelonitrile and (o, m,
p)-chloromandelonitrile, whereas replacing it with leucine abolished its
activity. The best mutant S190G exhibited threefold higher specific activity
toward mandelonitrile compared with that of wild-type nitA, which rendered it
promising for industrial application. Homology modeling and molecular docking
experiments were in agreement with the kinetic assays and support the improved
catalytic performance.
PMID- 28687859
TI - Impact of a discordant helix on beta-amyloid structure, aggregation ability and
toxicity.
AB - According to amyloid cascade hypothesis, the deposit of amyloid-beta (Abeta)
peptide is the main cause of Alzheimer's disease (AD). The aggregation ability
and toxicity of Abeta peptides are highly associated with the sequence and
conformation. A discordant helix is a helical segment with a tendency to form a
beta-strand conformation and has been found in many amyloid-like proteins or
peptides. In this review, we summarize the current knowledge of the properties of
a Abeta discordant helix and its impact on the Abeta structure, aggregation
ability and cytotoxicity. In an Abeta sequence, a discordant helical region
located at residue 15-26 has been proposed. This discordant helix plays a vital
role in Abeta conformation, aggregation ability and cytotoxicity. Any factors
which can stabilize the structure of the discordant helix may lead to the
prevention of aggregation and toxicity of Abeta. This makes the discordant helix
an attractive target for the design of new drugs for the treatment of AD.
PMID- 28687860
TI - Are more trials of calcium supplements really needed? A response to Bolland et
al.
PMID- 28687858
TI - A genomic perspective on HLA evolution.
AB - Several decades of research have convincingly shown that classical human
leukocyte antigen (HLA) loci bear signatures of natural selection. Despite this
conclusion, many questions remain regarding the type of selective regime acting
on these loci, the time frame at which selection acts, and the functional
connections between genetic variability and natural selection. In this review, we
argue that genomic datasets, in particular those generated by next-generation
sequencing (NGS) at the population scale, are transforming our understanding of
HLA evolution. We show that genomewide data can be used to perform robust and
powerful tests for selection, capable of identifying both positive and balancing
selection at HLA genes. Importantly, these tests have shown that natural
selection can be identified at both recent and ancient timescales. We discuss how
findings from genomewide association studies impact the evolutionary study of HLA
genes, and how genomic data can be used to survey adaptive change involving
interaction at multiple loci. We discuss the methodological developments which
are necessary to correctly interpret genomic analyses involving the HLA region.
These developments include adapting the NGS analysis framework so as to deal with
the highly polymorphic HLA data, as well as developing tools and theory to search
for signatures of selection, quantify differentiation, and measure admixture
within the HLA region. Finally, we show that high throughput analysis of
molecular phenotypes for HLA genes-namely transcription levels-is now a feasible
approach and can add another dimension to the study of genetic variation.
PMID- 28687861
TI - Are more trials of calcium supplements really needed?
PMID- 28687863
TI - Erratum to: Perseveration in a spatial-discrimination serial reversal learning
task is differentially affected by MAO-A and MAO-B inhibition and associated with
reduced anxiety and peripheral serotonin levels.
PMID- 28687862
TI - No superior surgical treatment for secondary osteochondral defects of the talus.
AB - PURPOSE: The purpose of this systematic review was to identify the most effective
surgical treatment for talar osteochondral defects after failed primary surgery.
METHODS: A literature search was conducted to find studies published from January
1996 till July 2016 using PubMed (MEDLINE), EMBASE, CDSR, DARE and CENTRAL. Two
authors screened the search results separately and conducted quality assessment
independently using the Newcastle-Ottawa scale. Weighted success rates were
calculated. Studies eligible for pooling were combined. RESULTS: Twenty-one
studies with a total of 299 patients with 301 talar OCDs that failed primary
surgery were investigated. Eight studies were retrospective case series, twelve
were prospective case series and there was one randomized controlled trial.
Calculated success percentages varied widely and ranged from 17 to 100%. Because
of the low level of evidence and the scarce number of patients, no
methodologically proper meta-analysis could be performed. A simplified pooling
method resulted in a calculated mean success rate of 90% [CI 82-95%] for the
osteochondral autograft transfer procedure, 65% [CI 46-81%] for mosaicplasty and
55% [CI 40-70%] for the osteochondral allograft transfer procedure. There was no
significant difference between classic autologous chondrocyte implantation
(success rate of 59% [CI 39-77%]) and matrix-associated chondrocyte implantation
(success rate of 73% [CI 56-85%]). CONCLUSIONS: Multiple surgical treatments are
used for talar OCDs after primary surgical failure. More invasive methods are
administered in comparison with primary treatment. No methodologically proper
meta-analysis could be performed because of the low level of evidence and the
limited number of patients. It is therefore inappropriate to draw firm
conclusions from the collected results. Besides an expected difference in outcome
between the autograft transfer procedure and the more extensive procedures of
mosaicplasty and the use of an allograft, neither a clear nor a significant
difference between treatment options could be demonstrated. The need for
sufficiently powered prospective investigations in a randomized comparative
clinical setting remains high. This present systematic review can be used in
order to inform patients about expected outcome of the different treatment
methods used after failed primary surgery. LEVEL OF EVIDENCE: IV.
PMID- 28687865
TI - [Forefoot relief with shoe inserts : Effects of different construction
strategies].
AB - BACKGROUND: Shoe inserts and shoe modifications are used to reduce plantar peak
pressure. The effects of different shoe inserts and shoe construction strategies
for relief of the forefoot have not yet been sufficiently evaluated. PURPOSE: The
aim of this study was to analyze the effects of shoe inserts and shoe
construction strategies (e.g. metatarsal pad, forefoot cushioning and control)
and shoe modifications (e.g. flexible or stiff) on the peak plantar pressure in
the forefoot region. MATERIAL AND METHODS: In this study 15 healthy subjects were
recruited. Plantar pressure distribution was measured using an in-shoe system
during walking (3.5km?h-1) on a treadmill and the average plantar peak pressure
(kPa) in the forefoot was calculated. The statistics for testing the hypothesis
were carried out using 2-factorial ANOVA with repeat measurements (factors: shoe,
insert; alpha = 0.05). RESULTS: The metatarsal pad and forefoot cushioning led to
a reduction of peak pressure, which was statistically significant compared to the
control condition (p = 0.009). No differences were observed between both shoe
inserts (p > 0.05). A comparison between stiff and flexible shoes revealed a
statistically significant pressure reduction in favor of stiff shoes (p =
0.0001). The metatarsal pad led to a peak pressure increase in the midfoot of 12%
and by 21% compared to control and forefoot cushioning, respectively. DISCUSSION:
A peak pressure reduction in the forefoot can be achieved with a metatarsal pad
or with cushioning; however, the metatarsal pad resulted in a subsequent increase
in midfoot pressure. Moreover, shoe construction is crucial because a stiff shoe
contributes to a better peak pressure reduction compared to a flexible shoe.
Prospective clinical studies should be carried out to prove whether this results
in beneficial effects for patients with metatarsalgia.
PMID- 28687864
TI - Stressed podocytes-mechanical forces, sensors, signaling and response.
AB - Increased glomerular capillary pressure (glomerular hypertension) and increased
glomerular filtration rate (glomerular hyperfiltration) have been proven to cause
glomerulosclerosis in animal models and are likely to be operative in patients.
Since podocytes cover the glomerular basement membrane, they are exposed to
tensile stress due to circumferential wall tension and to fluid shear stress
arising from filtrate flow through the narrow filtration slits and through
Bowman's space. In vitro evidence documents that podocytes respond to tensile
stress as well as to fluid shear stress. Several proteins are discussed in this
review that are expressed in podocytes and could act as mechanosensors converting
mechanical force via a conformational change into a biochemical signal. The
cation channels P2X4 and TRPC6 were shown to be involved in mechanosignaling in
podocytes. P2X4 is activated by stretch-induced ATP release, while TRPC6 might be
inherently mechanosensitive. Membrane, slit diaphragm and cell-matrix contact
proteins are connected to the sublemmal actin network in podocytes via various
linker proteins. Therefore, actin-associated proteins, like the proven
mechanosensor filamin, are ideal candidates to sense forces in the podocyte
cytoskeleton. Furthermore, podocytes express talin, p130Cas, and fibronectin that
are known to undergo a conformational change in response to mechanical force
exposing cryptic binding sites. Downstream of mechanosensors, experimental
evidence suggests the involvement of MAP kinases, Ca2+ and COX2 in
mechanosignaling and an emerging role of YAP/TAZ. In summary, our understanding
of mechanotransduction in podocytes is still sketchy, but future progress holds
promise to identify targets to alleviate conditions of increased mechanical load.
PMID- 28687867
TI - Effect of Multi-walled Carbon Nanotubes on Metabolism and Morphology of
Filamentous Green Microalgae.
AB - Multi-walled carbon nanotubes (MWCNTs) have potential applications in the
industrial, agricultural, pharmaceutical, medical, and environmental remediation
fields. However, many uncertainties exist regarding the environmental
implications of engineered nanomaterials. This study examined the effect of the
MWCNTs on metabolic status and morphology of filamentous green microalgae
Klebsormidium flaccidum. Appropriate concentrations of MWCNT (1, 50, and 100 MUg
mL-1) were added to a microalgal culture in the exponential growth phase and
incubated for 24, 48, 72, and 96 h. Exposure to MWCNT led to reductions in algal
growth after 48 h and decreased on cell viability for all experimental endpoints
except for 1 ug mL-1 at 24 h and 100 ug mL-1 after 72 h. At 100 ug mL-1, MWCNTs
induced reactive oxygen species (ROS) production and had an effect on
intracellular adenosine triphosphate (ATP) content depending on concentration and
time. No photosynthetic activity variation was observed. Observations by scanning
transmission electron microscopy showed cell damage. In conclusion, we have
demonstrated that exposure to MWCNTs affects cell metabolism and microalgal cell
morphology. To our best knowledge, this is the first case in which MWCNTs exhibit
adverse effects on filamentous green microalgae K. flaccidum. These results
contribute to elucidate the mechanism of MWCNT nanotoxicity in the bioindicator
organism of terrestrial and freshwater habitats.
PMID- 28687866
TI - Quantification, improvement, and harmonization of small lesion detection with
state-of-the-art PET.
AB - In recent years, there have been multiple advances in positron emission
tomography/computed tomography (PET/CT) that improve cancer imaging. The present
generation of PET/CT scanners introduces new hardware, software, and acquisition
methods. This review describes these new developments, which include time-of
flight (TOF), point-spread-function (PSF), maximum-a-posteriori (MAP) based
reconstruction, smaller voxels, respiratory gating, metal artefact reduction, and
administration of quadratic weight-dependent 18F-fluorodeoxyglucose (FDG)
activity. Also, hardware developments such as continuous bed motion (CBM),
(digital) solid-state photodetectors and combined PET and magnetic resonance (MR)
systems are explained. These novel techniques have a significant impact on cancer
imaging, as they result in better image quality, improved small lesion
detectability, and more accurate quantification of radiopharmaceutical uptake.
This influences cancer diagnosis and staging, as well as therapy response
monitoring and radiotherapy planning. Finally, the possible impact of these
developments on the European Association of Nuclear Medicine (EANM) guidelines
and EANM Research Ltd. (EARL) accreditation for FDG-PET/CT tumor imaging is
discussed.
PMID- 28687868
TI - Comparative Toxicity of Two Chemical Dispersants and Dispersed Oil in Estuarine
Organisms.
AB - Chemical dispersants can be a useful tool to mitigate oil spills. This study
examined potential risks to sensitive estuarine species by comparing the toxicity
of two dispersants (Corexit(r) EC9500A and Finasol(r) OSR 52) individually and in
chemically enhanced water-accommodated fractions (CEWAFs) of Louisiana Sweet
Crude oil. Acute toxicity thresholds and sublethal biomarker responses were
determined in seven species (sheepshead minnow, grass shrimp, mysid, amphipod,
polychaete, hard clam, mud snail). Comparing median lethal (LC50) values for the
dispersants, Finasol was generally more toxic than Corexit and had greater
sublethal toxicity (impaired embryonic hatching, increased lipid peroxidation,
decreased acetylcholinesterase activity). The nominal concentration-based mean
LC50 for all species tested with Corexit was 150.31 mg/L compared with 43.27 mg/L
with Finasol. Comparing the toxicity of the CEWAFs using the nominal
concentrations (% CEWAF), Corexit-CEWAFs appeared more toxic than Finasol-CEWAFs;
however, when LC50 values were calculated using measured hydrocarbon
concentrations, the Finasol-CEWAFs were more toxic. There was greater dispersion
efficiency leading to greater hydrocarbon concentrations measured in the Corexit
CEWAF solutions than in equivalent Finasol-CEWAF solutions. The measured
concentration-based mean LC50 values for all species tested with Corexit-CEWAF
were 261.96 mg/L total extractable hydrocarbons (TEH) and 2.95 mg/L total
polycyclic aromatic hydrocarbons (PAH), whereas the mean LC50 values for all
species tested with Finasol-CEWAF were 23.19 mg/L TEH and 0.49 mg/L total PAH.
Larval life stages were generally more sensitive to dispersants and dispersed oil
than adult life stages within a species. These results will help to inform
management decisions regarding the use of oil-spill dispersants.
PMID- 28687869
TI - The Influence of Oropalatal Dimensions on the Measurement of Tongue Strength.
AB - Tongue strength is routinely evaluated in clinical swallowing evaluations since
lingual weakness is an established contributor to dysphagia. Tongue strength may
be clinically quantified by the maximum isometric tongue pressure (MIP) generated
by the tongue against the palate; however, wide ranges in normal performance
remain to be fully explained. Although orthodontic theory has long suggested a
relation between lingual function and oral cavity dimensions, little attention
has been given to the potential influence of oral and palatal structure(s) on
healthy variance in MIP generation. Therefore, anterior and posterior tongue
strength measures and oropalatal dimensions were obtained across 147 healthy
adults (aged 18-88 years). Age was confirmed as a significant, independent
predictor explaining approximately 10.2% of the variance in anterior tongue
strength, but not a significant predictor of posterior tongue strength. However,
oropalatal dimensions predicted anterior tongue strength with over three times
the predictive power of age alone (p < .001). Significant models for anterior
tongue strength (R 2 = .457) and posterior tongue strength (R 2 = .283) included
a combination of demographic predictors (i.e., age and/or gender) and oropalatal
dimensions. Palatal width, estimated tongue volume, and gender were significant
predictors of posterior tongue strength (p < .001). Therefore, oropalatal
dimensions may warrant consideration when accurately differentiating between
pathological lingual weakness and healthy individual difference.
PMID- 28687870
TI - [Genuine motor phenomena in schizophrenic psychoses : Theoretical background and
definition of context].
AB - Besides positive and negative symptoms, motor abnormalities have been
increasingly recognized as central symptoms of schizophrenia. Recent
investigations of antipsychotic-naive first-episode patients with schizophrenia
found significantly higher rates of genuine motor abnormalities (GMA) when
compared to healthy individuals. The first part of this article introduces the
historical and clinical background of GMA in schizophrenia. In the second part
the relevance of scientific research and clinical implication of GMA in
schizophrenia are discussed. Finally, this article aims at presenting a
conceptual framework and a reference system involving both genuine and drug
induced motor abnormalities. The future clinical implications of GMA research are
presented and multimodal and transdiagnostic studies are advocated. Future
research on GMA will not only essentially enrich the formation of psychiatric
theories but also promote progress in clinical neuroscience.
PMID- 28687872
TI - High-frequency aflibercept injections in persistent neovascular age-related
macular degeneration.
PMID- 28687871
TI - Chromatic pupillography in hemianopia patients with homonymous visual field
defects.
AB - PURPOSE: The pupil light reflex is considered to be a simple subcortical reflex.
However, many studies have proven that patients with isolated occipital lesions
with homonymous hemianopia show pupillary hemihypokinesia. Our hypothesis is that
the afferent pupillary system consists of two pathways: one via intrinsically
photosensitive retinal ganglion cells (ipRGCs), the other running through the
normal RGCs via the visual cortex. The purpose of this study was to test the
hypothesis of these two separate pupillomotor pathways. METHODS: 12 patients
(59.1 +/- 18.8 years) with homonymous hemianopia due to post-geniculate lesions
of the visual pathway and 20 normal controls (58.6 +/- 12.9 years) were examined
using chromatic pupillography: stimulus intensity was 28 lx corneal illumination,
stimulus duration was 4.0 s, and the stimulus wavelengths were 420 +/- 20 nm
(blue) and 605 +/- 20 nm (red), respectively. The examined parameters were
baseline pupil diameter, latency, and relative amplitudes (absolute amplitudes
compared to baseline), measured at maximal constriction, at 3 s after stimulus
onset, at stimulus offset, and at 3 s and 7 s after stimulus offset. RESULTS: The
relative amplitudes for the red stimulus were significantly smaller for
hemianopia patients compared to the normal controls [maximal constriction: 35.6
+/- 5.9% (hemianopia) to 42.3 +/- 5.7% (normal); p = 0.004; 3 s after stimulus
onset: p = 0.004; stimulus offset: p = 0.001]. No significant differences in any
parameter were found between the two groups using the blue stimulus. CONCLUSIONS:
The results support the hypothesis that the ipRGC pathway is mainly subcortical,
whereas a second, non-ipRGC pathway via the occipital cortex exists.
PMID- 28687874
TI - Winners and Losers: Allocating Scare Resources for Patients with Hepatocellular
Carcinoma.
PMID- 28687873
TI - alpha2,6-linked sialic acid serves as a high-affinity receptor for cancer
oncolytic virotherapy with Newcastle disease virus.
AB - PURPOSE: Newcastle disease virus (NDV) has been applied to oncolytic virotherapy
for decades due to its naturally oncolytic property. In spite of the
substantiation of the sialic acid receptors of NDV on host cells, knowledge of
preference of sialic acid linkage in viral attachment and oncolytic effect is
lacking and imperative to be elucidated. METHODS: Surface plasmon resonance
analysis and competitive inhibition with sialylated glycan receptor analogues
were used to determine the affinity and the preference of sialic acid receptor.
Treatments of sialyltransferase inhibitors and linkage-specific sialidases and
transfection with sialyltransferase expression vector were performed to regulate
sialic acids levels. RESULTS: We demonstrated that sialic acid was essential for
NDV binding and infection of tumor cells. alpha2,6-linked sialic acid served as a
high-affinity receptor for NDV and the ST6Gal I sialyltransferase that
synthesizes alpha2-6 linkage of sialylated N-linked glycans in CHO-K1 cells
promoted NDV binding and cytopathic effect. More importantly, an enhanced
antitumor effect of NDV on aggressive SW620 colorectal carcinoma cells with high
level of cell surface alpha2,6-sialylation, but not SW480 cells with relative low
level of alpha2,6-sialylation, was observed both in vitro and in vivo.
CONCLUSIONS: The study provides evidence of optimized therapeutic strategy in
oncolytic virotherapy via partly defining alpha2,6-sialylated receptor as a
"cellular marker" for NDV.
PMID- 28687875
TI - Oncologic Outcome of Metastasectomy for Urothelial Carcinoma: Who Is the Best
Candidate?
AB - BACKGROUND: Resection of metastatic lesions (metastasectomy) is performed for
highly selected patients with metastatic urothelial carcinoma (mUC). This study
aimed to identify the clinicopathologic factors associated with oncologic outcome
for patients who underwent metastasectomy for mUC. METHODS: This analysis
included 37 UC patients who underwent metastasectomy with curative intent at nine
Japanese hospitals. The primary end point was cancer-specific survival. The
Kaplan-Meier method with the log-rank test and the multivariable Cox proportional
hazards model addressed the relationship between clinical characteristics and
survival. RESULTS: Metastasectomy was performed for pulmonary (n = 23), nodal (n
= 7), and other (n = 7) metastases. The median survival time was 35.4 months
(interquartile range [IQR] 15.5, not reached) from the detection of metastasis
and 34.3 months (IQR 13.1, not reached) from metastasectomy. The 5-year cancer
specific survival rate after detection of metastasis was 39.7%. In the
multivariate analysis, the time from primary surgery to detection of metastasis
(time-to-recurrence [TTR]) of 15 months or longer (hazard ratio [HR] 0.23; p =
0.0063), no symptoms of recurrence (HR 0.23; p = 0.0126), and serum C-reactive
protein (CRP) levels lower than than 0.5 mg/dl (HR 0.24; p = 0.0052) were
significantly associated with better survival. CONCLUSIONS: Long-term survival
could be achieved for some patients with mUC who underwent metastasectomy. Lung
and lymph nodes were predominant sites for metastasectomy. Symptoms, TTR, and CRP
value were identified as associated with survival and should be taken into
account when metastasectomy is considered.
PMID- 28687877
TI - A simple and sensitive surface-enhanced Raman spectroscopic discriminative
detection of organophosphorous nerve agents.
AB - Organophosphorous nerve agents (NAs) pose a great threat to nations and people
because of their acute and extreme toxicities. The rapid detection of NAs has
attracted growing interest in the first emergency response field. In this work,
we demonstrate a simple and sensitive surface-enhanced Raman spectroscopic (SERS)
method for NAs detection, and G- and V-agents discrimination. The results show
that VX (V-agents) can be directly detected at a 20 ng mL-1 level with pinhole
shell-isolated gold nanoparticles (pinSHINs) as the substrate. Moreover, combined
with a specific and prompt alkaline keto-oxime transformation approach in a full
aqueous solution, G-agents can be measured as low as 10 ng mL-1 with excellent
discrimination from V-agents and other common organophosphorous pesticides within
several minutes. The achieved discriminative detection of G-agents and VX could
be significant not only for reducing the false positive and negative signals but
also for providing an appropriate recommendation on the effective medical rescue.
A decontamination outcome occurred alongside, any highly toxic G-agents were
converted to a less toxic phosphate, and the generated cyanide was fully and
firmly adsorbed onto the surface of pinSHINs substrate, which may be further used
for on-site detection of extremely toxic NA prototypes. Graphical abstract ?.
PMID- 28687876
TI - Chromosome 21-Encoded microRNAs (mRNAs): Impact on Down's Syndrome and Trisomy-21
Linked Disease.
AB - Down's syndrome (DS; also known as trisomy 21; T21) is caused by a triplication
of all or part of human chromosome 21 (chr21). DS is the most common genetic
cause of intellectual disability attributable to a naturally-occurring imbalance
in gene dosage. DS incurs huge medical, healthcare, and socioeconomic costs, and
there are as yet no effective treatments for this incapacitating human
neurogenetic disorder. There is a remarkably wide variability in the 'phenotypic
spectrum' associated with DS; the progression of symptoms and the age of DS onset
fluctuate, and there is further variability in the biophysical nature of the
chr21 duplication. Besides the cognitive disruptions and dementia in DS patients
other serious health problems such as atherosclerosis, altered lipogenesis,
Alzheimer's disease, amyotrophic lateral sclerosis (Lou Gehrig's disease),
autoimmune disease, various cancers including lymphoma, leukemia, glioma and
glioblastoma, status epilepticus, congenital heart disease, hypotonia, manic
depression, prostate cancer, Usher syndrome, motor disorders, Hirschsprung
disease, and various physical anomalies such as early aging occur at elevated
frequencies, and all are part of the DS 'phenotypic spectrum.' This communication
will review the genetic link between these fore-mentioned diseases and a small
group of just five stress-associated microRNAs (miRNAs)-that include let-7c,
miRNA-99a, miRNA-125b, miRNA-155, and miRNA-802-encoded and clustered on the long
arm of human chr21 and spanning the chr21q21.1-chr21q21.3 region.
PMID- 28687878
TI - Suitability of DPPH spiking for antioxidant screening in natural products: the
example of galloyl derivatives from red maple bark extract.
AB - To investigate the antioxidant potential in natural products, radical scavenging
tests (ABTS, DPPH, ORAC, etc.) are usually considered as the first approach. In
addition to the standard colorimetric assays, methods using separation techniques
(on-line and pre-column assays) have been developed in the past decades. Based on
the peak area (PA) reductions of compounds monitored by HPLC, the pre-column
spiking method allows rapid characterisation of natural matrices avoiding
laborious isolation steps. However, available information about the significance
of the results produced remains scarce. Here, we report, for the first time, a
discussion of the potential of the pre-column DPPH spiking method to pinpoint
antioxidant compounds using red maple bark extract (RMBE). First, DPPH spiking
was conventionally applied to the galloyl compounds in the extract showing the
inadequacy of assessing results by PA reductions. The method was then applied to
pure galloyl derivatives, evaluating their molar amount reacted (MAR) for more
significance. The comparison with the standard DPPH-HPLC/AE method directly
monitoring DPPH* inhibition highlighted the inability to retrieve the respective
antioxidant efficiencies (AE) of each compound by using DPPH spiking. Despite its
limitations, the DPPH spiking method brought to light an autoxidation phenomenon
and a matrix/mixture effect investigated through tertiary mixtures of galloyl
compounds. Although restricted to the compounds from one natural matrix, this
study questions the validity of the spiking method as usually performed and could
serve as a basis for further investigations (explorations of other natural
products, kinetics considerations). Graphical abstract Investigation of the pre
column DPPH spiking method through the case of galloyl derivatives.
PMID- 28687879
TI - Dynamic-SERS spectroscopy for the in situ discrimination of xanthine analogues in
ternary mixture.
AB - Nowadays, there is a growing demand for analytical methods capable of providing
rapid and simple identification of certain compounds in complex samples without a
time-consuming separation process. In this report, a combinative strategy of
dynamic surface-enhanced Raman scattering (DSERS) and two-dimensional correlation
spectroscopy (2DCOS) analysis was demonstrated for the in situ identification of
xanthine analogues in their ternary mixture. The DSERS method with an optimized
initial pH value allows monitoring the distinct pH-dependent spectral evolution
among analogues in real time, enhancing the spectral selectivity. Moreover,
complex variations in pH-dependent spectral sets were further interpreted by
2DCOS. Consequently, xanthine analogues in their ternary mixture were
distinguished from each other on the basis of characteristic peaks in 2DCOS maps.
This combined strategy between DSERS and 2DCOS offers a prospect in studies of in
situ analysis of structural analogues involving mixture specimens. Graphical
abstract Schematic diagram illustrating the collection of pH-dependent SERS
spectra by dynamic-SERS method, the procedure of two-dimensional correlation
analysis and the identification basing on asynchronous maps.
PMID- 28687880
TI - Sulfonate-terminated carbosilane dendron-coated nanotubes: a greener point of
view in protein sample preparation.
AB - Reduction or removal of solvents and reagents in protein sample preparation is a
requirement. Dendrimers can strongly interact with proteins and have great
potential as a greener alternative to conventional methods used in protein sample
preparation. This work proposes the use of single-walled carbon nanotubes
(SWCNTs) functionalized with carbosilane dendrons with sulfonate groups for
protein sample preparation and shows the successful application of the proposed
methodology to extract proteins from a complex matrix. SEM images of nanotubes
and mixtures of nanotubes and proteins were taken. Moreover, intrinsic
fluorescence intensity of proteins was monitored to observe the most significant
interactions at increasing dendron generations under neutral and basic pHs.
Different conditions for the disruption of interactions between proteins and
nanotubes after protein extraction and different concentrations of the disrupting
reagent and the nanotube were also tried. Compatibility of extraction and
disrupting conditions with the enzymatic digestion of proteins for obtaining
bioactive peptides was also studied. Finally, sulfonate-terminated carbosilane
dendron-coated SWCNTs enabled the extraction of proteins from a complex sample
without using non-environmentally friendly solvents that were required so far.
Graphical Abstract Green protein extraction from a complex sample employing
carbosilane dendron coated nanotubes.
PMID- 28687881
TI - Perspectives and challenges of photon-upconversion nanoparticles - Part II:
bioanalytical applications.
AB - In Part II of this review series on lanthanide-doped photon-upconversion
nanoparticles (UCNPs), we present and critically discuss the performance and
suitability of UCNPs as background-free luminescent reporters in bioimaging and
bioanalytical applications. The preparation of a biocompatible nanoparticle
surface is an integral step for all life - science-related applications. UCNPs
have found their way into a large number of diagnostic platforms, homogeneous and
heterogeneous assay formats, and sensor applications. Many bioanalytical
detection schemes involve Forster resonance energy transfer (FRET), which is
still debated for UCNPs and needs to be much improved. The need for dedicated and
standardized instruments as well as recent studies on the dissolution and
potential toxicity of UCNPs are addressed. Finally we outline future trends and
challenges in the field of upconversion. Graphical Abstract Both synthesis /
spectroscopy as well bioanalytical applications of UCNPs are driven by the COST
Action CM1403 "The European Upconversion Network".
PMID- 28687882
TI - Determination of benzothiazoles in seafood species by subcritical water
extraction followed by solid-phase microextraction-gas chromatography-tandem mass
spectrometry: estimating the dietary intake.
AB - Benzothiazoles are high production volume chemicals widely used in many
industrial and household applications. However, information on their occurrence
in aquatic organisms is very limited, although a high level of bioaccumulation is
expected. In this study and for the first time, a method was developed involving
subcritical water extraction followed by solid-phase microextraction coupled to
gas chromatography-ion trap-tandem mass spectrometry for the determination of
five benzothiazoles in seafood. The repeatability and reproducibility of the
method were under 21% (%RSD, n = 5, 100 ng g-1 (dw)), while method detection
limits and method quantification limits were between 0.5 and 10 ng g-1 (dw) and 1
and 50 ng g-1 (dw), respectively. Ten widely consumed fish and shellfish species
from the county of Tarragona (Catalonia, Spain) were selected in order to
estimate dietary exposure and to assess the human health risks. The most
frequently determined compounds were benzothiazole and 2-(methylthio)
benzothiazole, with squid being the species which showed the highest level of
benzothiazole (82 ng g-1 (dw)). In terms of human exposure, the current
concentrations of benzothiazoles found in fish and shellfish could not be
compared to threshold values because of the lack of toxicological data.
PMID- 28687883
TI - Combination of MALDI-MSI and cassette dosing for evaluation of drug distribution
in human skin explant.
AB - Study of skin penetration and distribution of the drug compounds in the skin is a
major challenge in the development of topical drug products for treatment of skin
diseases. It is crucial to have fast and efficacious screening methods which can
provide information concerning the skin penetration and the distribution of the
drug molecules in the region of the target. Mass spectrometry imaging (MSI) such
as matrix-assisted laser desorption/ionization (MALDI)-MSI offers the opportunity
to analyze the drug distribution at micrometer scale, but is a low throughput
technique. Cassette dosing of drug molecules has been widely used for two decades
as a high throughput screening tool for plasma pharmacokinetic analysis. The
purpose of this study is to evaluate the utility of combining MALDI-MSI with
cassette dosing to obtain a medium throughput screening technique for drug
distribution in the skin directly from thin tissue sections. Excised fresh human
skin was treated with two different formulation types containing both single
drugs and a cassette with four drugs. Biopsies were taken and analyzed with
traditional UHPLC-MS/MS and MALDI-MSI. The results reveal that skin penetration
data of the four drugs administered together were in agreement with skin
penetration data obtained when the molecules were administered individually.
Furthermore, the MALDI-MSI data reveal different distribution profiles of the
four drugs which were not possible to deduce from the UHPLC-MS/MS bioanalysis.
These findings suggest that combination of MALDI-MSI and cassette dosing can be
used as a medium throughput screening tool at an early stage in the drug
discovery/development process. Graphical abstract Investigation of drug
distribution in human skin explant by MALDI-MSI after cassette dosing.
PMID- 28687884
TI - Synthesis of triangular silver nanoprisms and spectroscopic analysis on the
interaction with bovine serum albumin.
AB - The interactions of triangular silver nanoprisms (TAgNPrs) with bovine serum
albumin (BSA) were investigated using multiple spectroscopic techniques. A
noticeable absorbance increase was noted in the peak ranges of 250 to 300 nm for
BSA, and the intensity increased with the increasing concentration of TAgNPrs.
Furthermore, a slight blue shift of the surface plasmon resonance band of TAgNPrs
occurred, indicating that the protein absorbed on the TAgNPrs surface to form a
bio-nano interface. Analysis of fluorescence quenching data using the Stern
Volmer method revealed that static quenching takes place with complex formation.
Evaluation of thermodynamic parameter DeltaG theta for the binding processes
indicated that the binding reaction was exothermic. Furthermore, the values of
binding constant K revealed that the size of nanoparticles can affect the binding
degree. The order of binding affinity is 43.7 nm > 36.2 nm > 25.1 nm. The
competitive experiments of site markers (flufenamic acid and phenylbutazone)
suggested that the binding site of TAgNPrs on BSA was located in the region of
subdomain IIIA (Sudlow site II). In addition, the conformational changes of BSA
by TAgNPrs were analyzed by using synchronous fluorescence spectra, circular
dichroism, and three-dimensional fluorescence spectra. Graphical abstract The
protein absorbed on the TAgNPrs surface to form a nanoparticle-protein corona.
PMID- 28687885
TI - Determination of As, Se, and Hg in fuel samples by in-chamber chemical vapor
generation ICP OES using a Flow Blurring(r) multinebulizer.
AB - In this work, a new and simple analytical methodology based on in-chamber
chemical vapor generation has been developed for the spectrochemical analysis of
commercial fuel samples. A multiple nebulizer with three nebulization units has
been employed for this purpose: One unit was used for sample introduction, while
the other two were used for the necessary reagent introduction. In this way, the
aerosols were mixed inside the spray chamber. Through this method, analyte
transport and, therefore, sensitivity are improved in inductively coupled plasma
optical emission spectrometry. The factors (i.e., variables), influencing
chemical vapor generation, have been optimized using a multivariate approach.
Under optimum chemical vapor generation conditions ([NaBH4] = 1.39%, [HCl] = 2.97
M, total liquid flow = 936 MUL min-1), the proposed sample introduction system
allowed the determination of arsenic, selenium, and mercury up to 5 MUg g-1 with
a limit of detection of 25, 140, and 13 MUg kg-1, respectively. Analyzing spiked
commercial fuel samples, recovery values obtained were between 96 and 113%, and
expanded uncertainty values ranged from 4 to 16%. The most striking practical
conclusion of this investigation is that no carbon deposit appears on the plasma
torch after extended periods of working. Graphical abstract A new and simple
analytical methodology based on in-chamber chemical vapor generation has been
developed for the spectrochemical analysis of commercial fuel samples in ICP OES.
PMID- 28687886
TI - Sampling method development and optimization in view of human hand odor analysis
by thermal desorption coupled with gas chromatography and mass spectrometry.
AB - Forensic profiling of human odor is challenging and would be useful to support
information provided by dogs in courts of justice. Analyses of volatile compounds
constitutive of human odor are commonly performed with gas chromatography coupled
with mass spectrometry. All developed methods and sampling prototypes have to be
easy to use in the field by crime scene investigators. This paper will focus on
techniques for human hand odor sampling prior to analysis by a thermodesorption
device coupled with gas chromatography and mass spectrometry. Thermodesorption
and gas chromatography methods were developed using a sorbent phase spiked with a
mixture of 80 compounds representative of human hand odor. Then, the crucial
sampling step was performed indirectly with a homemade device based on air
suction and trapping on a sorbent. This indirect sampling device was evaluated
with the same synthetic mixture for optimization. An innovative polymer sorbent
called Sorb-Star(r) was compared to classic Tenax TA(r) packed tubes. Sorb
Star(r) provided similar recovery to Tenax TA(r) packed tubes and a smaller
pooled coefficient of variation (6 vs 13%). Thus, it appeared to be fully suited
to the indirect sampling of human hand odor. The developed methods were
successfully applied to real samples, the ultimate aim being the comparison of a
suspect's sample to a sample collected from a crime scene.
PMID- 28687887
TI - Ratiometric fluorescent pH nanoprobes based on in situ assembling of fluorescence
resonance energy transfer between fluorescent proteins.
AB - pH-dependent protein adsorption on mesoporous silica nanoparticle (MSN) was
examined as a unique means for pH monitoring. Assuming that the degree of protein
adsorption determines the distance separating protein molecules, we examined the
feasibility of nanoscale pH probes based on fluorescence resonance energy
transfer (FRET) between two fluorescent proteins (mTurquoise2 and mNeonGreen, as
donor and acceptor, respectively). Since protein adsorption on MSN is pH
sensitive, both fluorescent proteins were modified to make their isoelectric
points (pIs) identical, thus achieving comparable adsorption between the proteins
and enhancing FRET signals. The adsorption behaviors of such modified fluorescent
proteins were examined along with ratiometric FRET signal generation. Results
demonstrated that the pH probes could be manipulated to show feasible sensitivity
and selectivity for pH changes in hosting solutions, with a good linearity
observed in the pH range of 5.5-8.0. In a demonstration test, the pH probes were
successfully applied to monitor progress of enzymatic reactions. Such an "in situ
assembling" pH sensor demonstrates a promising strategy in developing nanoscale
fluorescent protein probes. Graphical abstract Working principle of the developed
pH sensor TNS; and FRET Ratio (I528/I460) as a function of pH under different
protein feed ratios (mNeonGreen to mTurquoise2).
PMID- 28687888
TI - Application of Appropriate Use Criteria for Initial Transthoracic
Echocardiography in an Academic Outpatient Pediatric Cardiology Program.
AB - Transthoracic echocardiography (TTE) is a non-invasive diagnostic modality for
children with suspected heart disease. The American College of Cardiology
published Appropriate Use Criteria (AUC) for an initial outpatient pediatric TTE
in 2014 to promote effective care and improve resource utilization. The objective
was to determine the appropriateness of TTE per the published AUC in a single
academic pediatric cardiology clinic as a baseline performance quality measure.
The echocardiography database was used to identify initial outpatient TTE in
children during January-March 2014. TTE indications (appropriate [A], may be
appropriate [M], or rarely appropriate [R]) and findings (normal, incidental, or
abnormal) were recorded. The effect of AUC and age groups on yield of abnormal
TTE findings was analyzed. Of the 2166 screened studies, our study cohort
consisted of 247 TTEs. Indications rated A, M, and R were found in 129, 27, and
90, respectively, and 1 was unclassifiable. Majority of TTE (n = 183) were
normal, although incidental findings were noted in 32 and abnormal findings in 32
cases. Abnormal findings were noted in 26/129 of A, 2/27 of M, and 4/90 of R.
Indications rated A were significantly associated with yield of abnormal TTE
findings, adjusted by age group. Infants and adolescents were more likely to have
abnormal TTE findings compared to young children. Recently published AUC were
validated for initial TTE in the outpatient pediatric cardiology clinic.
Appropriateness rated by AUC was highly associated with yield of abnormal TTE
findings and worked best in infants and adolescent.
PMID- 28687889
TI - Normal Reference Ranges for Pulmonary Artery Diameters in Preterm Infants.
AB - To establish normal reference ranges and Z-scores for pulmonary artery diameters
in preterm infants and their correlation with body surface area, body weight, and
chronological age. In a prospective study, 268 preterm infants, who fulfilled the
inclusion criteria were examined. Echocardiograms were performed to measure the
main pulmonary artery, right pulmonary artery, and left pulmonary artery
diameters on day(s) 0 to -6 of life and at weekly intervals until they reached 36
weeks of age. Body surface area was divided into thirteen groups from 0.07 to
0.19 m2. The mean gestational age was 29.8 (+/-2.38 SD) weeks, ranging between 24
and 35, the mean body weight was 1479 (+/-413 SD) grams, ranging between 588 and
3380, and the mean body surface area was 0.13 m2, ranging between 0.07 and 0.19
m2. All the pulmonary artery diameters correlated well with both body weight and
body surface area. Reference ranges, with mean +/- SD, range, and Z-scores for
aortic diameters according to body surface area were calculated. A significant
gradual increase was observed in main and branch pulmonary artery diameters with
increasing body surface area. Overall, a progressive and significant increase for
main and branch pulmonary artery diameters was observed during the first nine
weeks of life. The main and branch pulmonary artery diameters were found to have
significant correlation with body surface area. The study also provides reference
data with Z-scores, which can be used as a normal reference tool for measuring
the main pulmonary artery, right, and left pulmonary artery diameters of preterm
infants against body surface area.
PMID- 28687891
TI - Functional Analyses of a Novel CITED2 Nonsynonymous Mutation in Chinese Tibetan
Patients with Congenital Heart Disease.
AB - CITED2 gene is an important cardiac transcription factor that plays a fundamental
role in the formation and development of embryonic cardiovascular. Previous
studies have showed that knock-out of CITED2 in mice might result in various
cardiac malformations. However, the mechanisms of CITED2 mutation on congenital
heart disease (CHD) in Chinese Tibetan population are still poorly understood. In
the present study, 187 unrelated Tibetan patients with CHD and 200 unrelated
Tibetan healthy controls were screened for variants in the CITED2 gene; we
subsequently identified one potential disease-causing mutation p.G143A in a 6
year-old girl with PDA and functional analyses of the mutation were carried out.
Our study showed that the novel mutation of CITED2 significantly enhanced the
expression activity of vascular endothelial growth factor (VEGF) under the role
of co-receptor hypoxia inducible factor 1-aipha (HIF-1A), which is closely
related with embryonic cardiac development. As a result, CITED2 gene mutation may
play a significant role in the development of pediatric congenital heart disease.
PMID- 28687892
TI - Transcriptome and metabolome analysis of Ferula gummosa Boiss. to reveal major
biosynthetic pathways of galbanum compounds.
AB - Ferula gummosa Boiss. is an industrial and pharmaceutical plant that has been
highly recognized for its valuable oleo-gum-resin, namely galbanum. Despite the
fabulous value of galbanum, very little information on the genetic and
biochemical mechanisms of its production existed. In the present study, the oleo
gum-resin and four organs (root, flower, stem, and leaf) of F. gummosa were
assessed in terms of metabolic compositions and the expression of genes involved
in their biosynthetic pathways. Results showed that the most accumulation of
resin and essential oils were occurred in the roots (13.99 mg/g) and flowers
(6.01 mg/g), respectively. While the most dominant compound of the resin was beta
amyrin from triterpenes, the most abundant compounds of the essential oils were
alpha-pinene and beta-pinene from monoterpenes and alpha-eudesmol and germacrene
D from sesquiterpenes. Transcriptome analysis was performed by RNA sequencing
(RNA-seq) for the plant roots and flowers. Differential gene expression analysis
showed that 1172 unigenes were differential between two organs that 934 (79.6%)
of them were up-regulated in the flowers and 238 (20.4%) unigenes were up
regulated in the roots (FDR <=0.001). The most important up-regulated unigenes in
the roots were involved in the biosynthesis of the major components of galbanum,
including myrcene, germacrene-D, alpha-terpineol, and beta-amyrin. The results
obtained by RNA-Seq were confirmed by qPCR. These analyses showed that different
organs of F. gummosa are involved in the production of oleo-gum-resin, but the
roots are more active than other organs in terms of the biosynthesis of
triterpenes and some mono- and sesquiterpenes. This study provides rich molecular
and biochemical resources for further studies on molecular genetics and
functional genomics of oleo-gum-resin production in F. gummosa.
PMID- 28687893
TI - Erratum to: The role of gender and labour status in immunosenescence of 65+
Polish population.
PMID- 28687894
TI - On the Hegemony of Naturalized Violence: An Apology.
PMID- 28687895
TI - The Complexity of Family Reactions to Identity among Homeless and College
Lesbian, Gay, Bisexual, Transgender, and Queer Young Adults.
AB - Familial responses to lesbian, gay, bisexual, transgender, and queer (LGBTQ)
young people's identities range on a spectrum from rejection to acceptance and
these reactions strongly impact family relationships and young adult well-being.
Less is known, however, about how family members' reactions may differ based on
young people's contexts of socioeconomic status. Through a qualitative, life
course analysis of in-depth interview data from 46 LGBTQ college students and
LGBTQ homeless young adults, our study highlights the diverse, contextual nuances
of young people's "linked lives" within their families. We find that the context
of socioeconomic status influenced how a young person managed family rejection.
Conversely, processes of familial acceptance were also connected to life course
transitions that worked in some cases to enhance LGBTQ young adults' family
relationships. Finally, the intricacy of familial reactions to a young person's
LGBTQ identity transcended socioeconomic contexts as many respondents shared
similar experiences of rejection and acceptance. These findings have implications
for understanding how young people manage family relationships across different
contexts of socioeconomic status and how these experiences can shape their life
course trajectories. Results from this study can inform LGBTQ youth service
providers by tailoring intervention programs that account for contextual social
diversity.
PMID- 28687896
TI - Preben Hertoft (1928-2017).
PMID- 28687897
TI - Hypersexuality: A Critical Review and Introduction to the "Sexhavior Cycle".
AB - An empirical review of hypersexuality is timely as "compulsive sexual behavior"
is being considered as an impulse control disorder for inclusion in the
forthcoming International Classification of Diseases, 11th ed. Specifically,
hypersexuality has been conceptualized in the literature as the inability to
regulate one's sexual behavior that is a source of significant personal distress.
Various theoretical models have been posited in an attempt to understand the
occurrence of hypersexuality, although disagreement about these divergent
conceptualizations of the condition has made assessment and treatment of
hypersexual clients more challenging. Theories of sexual compulsivity, sexual
impulsivity, dual control (sexual inhibition/excitation), and sex addiction are
critically examined, as are the diagnostic criteria for clinically assessing
hypersexuality as a sexual disorder. Our discussion of hypersexuality covers a
diversity of research and clinical perspectives. We also address various
challenges associated with reliably defining, psychometrically measuring, and
diagnosing hypersexuality. Furthermore, literature is reviewed that expresses
concerns regarding whether hypersexuality (conceptualized as a disorder) exists,
whether it is simply normophilic behavior at the extreme end of sexual
functioning, or alternatively is a presenting problem that requires treatment
rather than a clinical diagnosis. Following our literature review, we developed
the "sexhavior cycle of hypersexuality" to potentially explain the
neuropsychology and maintenance cycle of hypersexuality. The sexhavior cycle
suggests that, for some hypersexual persons, high sexual arousal may temporarily
and adversely impact cognitive processing (cognitive abeyance) and explain a
repeated pattern of psychological distress when interpreting one's sexual
behavior (sexual incongruence). We also suggest that further research is required
to validate whether hypersexuality is a behavioral disorder (such as gambling),
although some presentations of the condition appear to be symptomatic of a
heterogeneous psychological problem that requires treatment.
PMID- 28687898
TI - A Time Series Analysis of Associations between Daily Temperature and Crime Events
in Philadelphia, Pennsylvania.
AB - Urban crime may be an important but overlooked public health impact of rising
ambient temperatures. We conducted a time series analysis of associations between
temperature and crimes in Philadelphia, PA, for years 2006-2015. We obtained
daily crime data from the Philadelphia Police Department, and hourly temperature
and dew point data from the National Centers for Environmental Information. We
calculated the mean daily heat index and daily deviations from each year's
seasonal mean heat index value. We used generalized additive models with a quasi
Poisson distribution, adjusted for day of the week, public holiday, and long-term
trends and seasonality, to estimate relative rates (RR) and 95% confidence
intervals. We found that the strongest associations were with violent crime and
disorderly conduct. For example, relative to the median of the distribution of
mean daily heat index values, the rate of violent crimes was 9% (95% CI 6-12%)
higher when the mean daily heat index was at the 99th percentile of the
distribution. There was a positive, linear relationship between deviations of the
daily mean heat index from the seasonal mean and rates of violent crime and
disorderly conduct, especially in cold months. Overall, these analyses suggest
that disorderly conduct and violent crimes are highest when temperatures are
comfortable, especially during cold months. This work provides important
information regarding the temporal patterns of crime activity.
PMID- 28687899
TI - Congenital solitary kidney in childhood: not so bad.
PMID- 28687900
TI - Life with one kidney: response to comments by Marzuillo and Polito.
PMID- 28687901
TI - Virological and Clinical Characteristics of Hepatitis B Virus Genotype A.
AB - Hepatitis B virus (HBV) infection is one of the most prevalent chronic viral
infections in humans. The overall prevalence of hepatitis B surface antigen
(HBsAg) is reported to be 3.6%; however, it varies depending upon the geographic
area. HBV is classified into ten genotypes (A through J) on the basis of an
intergroup genomic divergence of > 8%. Specifically, HBV genotype A exhibits
several unique virological and clinical characteristics and can be further
classified into seven subtypes. Among them, subtype A2 or Ae (A2/[e]) is
occasionally responsible for nosocomial infection and among homosexual males.
Regarding virological factors, the G1896A precore mutation is rarely observed in
genotype A as it would disrupt an essential stem-loop structure in the epsilon
signal essential for pregenomic RNA packaging. HBV genotype A also harbors a 6
nucleotide C-terminal insertion in the hepatitis B-e antigen (HBeAg) precursor,
resulting in a variable-length HBeAg protein product observed in serum of
positive patients. These molecular traits likely contribute to the specific
clinical presentation of genotype A-infected patients, such as mild acute
hepatitis B (AHB), longer persistence of HBsAg positivity in AHB, and increased
chronicity after AHB in adults. However, genotype A shows a better response to
interferon than other genotypes in chronic hepatitis B patients. Here, we review
the virological and clinical characteristics of HBV genotype A that will be
useful in elucidating the association among persistent viral infection, host
genetic factors, and treatment in future studies.
PMID- 28687902
TI - Decreased brain serotonin turnover rate following administration of Sharbat-e
Ahmed Shah produces antidepressant and anxiolytic effect in rats.
AB - Sharbat-e-Ahmed Shah (SAS) has usually been used in Traditional Unani Medicine
(TUM) for depression and insomnia but still not evaluated for its anti-depressant
and Neuropharmacological activity. In the present study, a Human dose of SAS (0.6
ml/kg/d) was administered orally to the rats for 15 consecutive days.
Antidepressant and anxiolytic were screened scientifically in rats by using
Forced swim test and light and dark box test. At the end of study high
performance liquid chromatographic (HPLC) method with electrochemical (EC)
detector was used for the measurement of blood and brain tryptophan and brain
serotonin levels. The present reported results are according to what is known in
TUM, where is prescribed as an antidepressant agent. After the administration,
SAS (at a human dose for 15 days) reduced the immobility time in rats analogous
to Imipramine (positive control) indicating the antidepressant effect of SAS. In
the present study, Diazepam or SAS (0.6 ml/kg/day) treated rats stayed in the
illuminated side of the light-dark box, as compare to control rats (Veh, 134.62
+/- 4.430 s; SAS 0.6 ml/kg, 192.2 +/- 8.11 s; DZP 1.0 mg/kg, 205.21.20 +/- 10.26
s, p < 0.05). It was also observed that SAS increased the availability of
tryptophan in blood and brain and hence increases 5-hydroxytryptamine (Serotonin:
5HT) in the brain. At the end, it was concluded that SAS contains some active
principles which increase the availability of neurochemical (tryptophan and 5HT)
and decrease the 5HT turnover rate thus causes antidepressant and anxiolytic
effects in experimental animals.
PMID- 28687903
TI - Prognostic values of cancer associated macrophage-like cells (CAML) enumeration
in metastatic breast cancer.
AB - PURPOSE: Circulating cancer associated macrophage-like cells (CAMLs) have been
detected in the peripheral blood of patients with solid tumors including breast
cancer. However, the prognostic relevance of CAMLs in metastatic breast cancer
(MBC) has not been evaluated. In the present study, we aimed to measure CAMLs and
circulating tumor cells (CTCs) at baseline and examine their prognostic value in
patients with MBC. METHODS: Peripheral blood samples from 127 MBC patients were
collected at baseline before starting a new treatment. The detection and
enumeration of CAMLs and CTCs in 7.5 ml whole blood were performed using the
CellSearchTM system. The associations of CAMLs and CTCs with the progression-free
survival (PFS) and overall survival (OS) in the patients were evaluated using
Kaplan-Meier curves and Cox proportional hazards modeling. RESULTS: Among 127 MBC
patients, 21 (16.5%) were detected with CAMLs and 38 (29.9%) had elevated CTCs
(>=5 CTCs/7.5 ml). Patients with CAMLs at baseline had worse PFS and OS with an
adjusted hazard ratio (HR) of 1.75 (95% CI 1.03-2.98, P = 0.0374) and 3.75 (95%
CI 1.52-9.26, P = 0.0042), compared to patients without CAMLs. Compared with
patients with <5 CTCs and without CAMLs, patients with <5 CTCs and with CAMLs,
with >=5 CTCs but without CAMLs, or with >=5 CTCs and with CAMLs, had an
increasing trend of risk of disease progression (HR = 0.84, 3.42 and 4.04
respectively, P for trend <0.0001) and death (HR = 2.66, 6.14, and 9.13,
respectively, P for trend <0.0001). CONCLUSION: Baseline enumeration of
individual CAMLs is an independent indicator for MBC patients' survival.
Evaluation of CAMLs in peripheral blood might provide a potential biomarker with
additional prognostic values over CTC enumeration alone in MBC patients.
PMID- 28687904
TI - A comparative genomic and transcriptomic analysis at the level of isolated root
hair cells reveals new conserved root hair regulatory elements.
AB - KEY MESSAGE: A comparative transcriptomic and genomic analysis between
Arabidopsis thaliana and Glycine max root hair genes reveals the evolution of the
expression of plant genes after speciation and whole genome duplication. Our
understanding of the conservation and divergence of the expression patterns of
genes between plant species is limited by the quality of the genomic and
transcriptomic resources available. Specifically, the transcriptomes generated
from plant organs are the reflection of the contribution of the different cell
types composing the samples weighted by their relative abundances in the sample.
These contributions can vary between plant species leading to the generation of
datasets which are difficult to compare. To gain a deeper understanding of the
evolution of gene transcription in and between plant species, we performed a
comparative transcriptomic and genomic analysis at the level of one single plant
cell type, the root hair cell, and between two model plants: Arabidopsis
(Arabidopsis thaliana) and soybean (Glycine max). These two species, which
diverged 90 million years ago, were selected as models based on the large amount
of genomic and root hair transcriptomic information currently available. Our
analysis revealed in detail the transcriptional divergence and conservation
between soybean paralogs (i.e., the soybean genome is the product of two
successive whole genome duplications) and between Arabidopsis and soybean
orthologs in this single plant cell type. Taking advantage of this evolutionary
study, we combined bioinformatics, molecular, cellular and microscopic tools to
characterize plant promoter sequences and the discovery of two root hair
regulatory elements (RHE1 and RHE2) consistently and specifically active in plant
root hair cells.
PMID- 28687906
TI - Development of the Implantable Resonator System for Clinical EPR Oximetry.
AB - Hypoxic tumors are more resistant to radiotherapy and chemotherapy, which
decreases the efficacy of these common forms of treatment. We have been
developing implantable paramagnetic particulates to measure oxygen in vivo using
electron paramagnetic resonance. Once implanted, oxygen can be measured
repeatedly and non-invasively in superficial tissues (<3 cm deep), using an
electron paramagnetic resonance spectrometer and an external surface-loop
resonator. To significantly extend the clinical applications of electron
paramagnetic resonance oximetry, we developed an implantable resonator system to
obtain measurements at deeper sites. This system has been used to successfully
obtain oxygen measurements in animal studies for several years. We report here on
recent developments needed to meet the regulatory requirements to make this
technology available for clinical use. radio frequency heating is discussed and
magnetic resonance compatibility testing of the device has been carried out by a
Good Laboratory Practice-certified laboratory. The geometry of the implantable
resonator has been modified to meet our focused goal of verifying safety and
efficacy for the proposed use of intracranial measurements and also for future
use in tissue sites other than the brain. We have encapsulated the device within
a smooth cylindrical-shaped silicone elastomer to prevent tissues from adhering
to the device and to limit perturbation of tissue during implantation and
removal. We have modified the configuration for simultaneously measuring oxygen
at multiple sites by developing a linear array of oxygen sensing probes, which
each provide independent measurements. If positive results are obtained in
additional studies which evaluate biocompatibility and chemical characterization,
we believe the implantable resonator will be at a suitable stage for initial
testing in human subjects.
PMID- 28687905
TI - Laparoscopic sacrohysteropexy versus vaginal hysterectomy for uterovaginal
prolapse using validated questionnaires: 2-year prospective study.
AB - INTRODUCTION: Surgical options for uterovaginal prolapse can be categorized into
uterus conservation-e.g., laparoscopic sacrohysteropexy (LSHP) or vaginal
hysterectomy (VH). There is insufficient reliable information on long-term
comparative outcomes of these procedures. The primary aim of this study was to
compare subjective and objective outcomes of LSHP and VH. The secondary aim was
to record adverse events, recurrent prolapse, and new-onset stress urinary
incontinence (SUI) up to 2 years. METHODS: Women with symptomatic uterovaginal
prolapse who opted for either LSHP or VH were included. Subjective outcomes were
compared at 1 and 2 years from baseline using the validated questionnaires.
Objective/anatomical outcomes using the Pelvic Organ Prolapse Quantification (POP
Q) system were assessed before and at 3 months after surgery. Adverse events,
recurrent prolapse, and new-onset SUI was recorded up to 2 years. RESULTS: The
study assessed 226 women with uterovaginal prolapse; 125 opted for surgery (44
LSHP, 81 VH). There was no statistically significant difference in symptom
domains between groups at baseline and 1 and 2 years. At 3 months POP-Q, greater
improvement was seen in points Ba and Ap in the LSHP group compared to VH group
and smaller genital hiatus was seen in the VH group. Adverse events, recurrent
prolapse, or new-onset SUI were not significantly different in the two groups.
CONCLUSIONS: Both LSHP and VH are effective surgical options for uterovaginal
prolapse. At 2 years, both procedures had similar improvement in symptom domains,
overall scores, adverse events, recurrent prolapse, and new-onset SUI. Long-term
randomized studies are needed.
PMID- 28687907
TI - Functional activation of Galphaq coupled to 5-HT2A receptor and M1 muscarinic
acetylcholine receptor in postmortem human cortical membranes.
AB - Heterotrimeric guanine nucleotide-binding proteins (G-proteins) play a pivotal
role in a wide range of signal transduction pathways, and receptor/G-protein
coupling has been implicated in the pathophysiology of mental disorders. In this
study, guanosine-5'-O-(3-[35S]thio)triphosphate ([35S]GTPgammaS)
binding/immunoprecipitation assay for Galphaq was applied to postmortem human
brains. After its optimization for human prefrontal cortical membranes, we
selected 5-hydroxytryptamine (5-HT) and carbachol as efficient agonists for
subsequent experiments. The concentration-response curve of 5-HT shifted towards
the right by the addition of increasing concentrations of ketanserin (with a pA 2
value of 9.18), indicating the involvement of the 5-HT2A receptor. Besides, the
carbachol-stimulated [35S]GTPgammaS binding to Galphaq was competitively
antagonized by telenzepine (with a pA 2 value of 8.81), indicating the
involvement of the M1 muscarinic acetylcholine receptor (mAChR). Concentration
response curves of 5-HT2A receptor- and M1 mAChR-mediated Galphaq activation were
determined in 40 subjects. The mean maximum percentage increase (%E max) was 155
and 470%, respectively, and the mean half-maximal effect concentration (EC50) was
131 nM and 15.2 uM, respectively. When the pharmacological parameters were
correlated with age, postmortem delay, freezing storage period, and tissue pH, no
statistically significant correlation was observed except for the negative
correlation between age and %E max value of carbachol-stimulated [35S]GTPgammaS
binding to Galphaq. The %E max values for 5-HT2A receptor- and M1 mAChR-mediated
Galphaq activation also tended to correlate with each other. These results
provide fundamental information of Galphaq-coupled 5-HT2A receptor and M1 mAChR
in native human brains, and lay the foundation for future studies in mental
disorder patients.
PMID- 28687908
TI - The effect of bilateral transcranial direct current stimulation on early auditory
processing in schizophrenia: a preliminary study.
AB - Transcranial direct current stimulation (tDCS) was applied bilaterally over the
auditory cortex in 12 schizophrenia patients to modulate early auditory
processing. Performance on a tone discrimination task (tone-matching task-TMT)
and auditory mismatch negativity were assessed after counterbalanced anodal,
cathodal, and sham tDCS. Cathodal stimulation improved TMT performance (p < 0.03)
compared to sham condition. Post-hoc analyses revealed a stimulation condition by
negative symptom interaction in which greater negative symptoms were associated
with a better TMT performance after anodal tDCS.
PMID- 28687909
TI - Post-clip placement MRI following second-look US-guided core biopsy for
suspicious lesions identified on breast MRI.
AB - OBJECTIVES: To evaluate whether the post-clip placement MRI following second-look
ultrasound (US)-guided core biopsy is useful to confirm the adequate sampling of
suspicious lesions identified on breast MRI. METHODS: Between 2014 and 2016, 31
consecutive women with 34 suspicious lesions that had not been identified on
previous mammography or US were detected using MRI. Among them, 26 women with 29
lesions (mean size 1.5 cm, range 0.5-5.8 cm) found by second-look US underwent US
guided biopsy, subsequent clip insertion and post-clip placement MRI. Five women
with five lesions that were not found by second-look US underwent MRI-guided
biopsy. The technical success rate and lesion characteristics were described.
RESULTS: The technical success rate was 96.6% (28/29). One failure case was a
benign, 1.1-cm non-mass enhancement. Of the 28 success cases, 23 (82.1%) were
masses and 5 (17.9%) were non-mass enhancements; 17 (60.7%) were benign, 4
(14.3%) were high-risk and 7 (25.0%) were malignant lesions. The technical
success rate was 100% (28/28) for masses and 83.3% (5/6) for non-mass
enhancements. CONCLUSIONS: Post-clip placement MRI following US-guided biopsy is
useful in confirming the adequate sampling of lesions identified on MRI. This
method could be an alternative to MRI-guided biopsy for lesions visible on US.
KEY POINTS: * Post-clip MRI is useful for confirming adequate sampling of US
guided biopsy. * Post-clip MRI following US-guided biopsy revealed a 96.6 %
technical success rate. * One technical failure case was a benign, 1.1-cm non
mass enhancement. * The technical success rate of US-guided biopsy for non-mass
enhancements was 83.3 %.
PMID- 28687910
TI - CT findings associated with survival in chronic hypersensitivity pneumonitis.
AB - OBJECTIVES: To identify CT findings in chronic hypersensitivity pneumonitis (cHP)
associated with survival. MATERIAL AND METHODS: Two thoracic radiologists
assessed CT scans for specific imaging findings and patterns in 132 subjects with
cHP. Survival analyses were performed. RESULTS: The majority of subjects had an
inconsistent with usual interstitial pneumonitis pattern on CT (55.3%,73/132).
Hypersensitivity pneumonitis (HP) diagnosis on CT was less common in those with
fibrosis (66.1%, 74/112) than those without fibrosis (85%,17/20). Smoking was
associated with a lower prevalence of HP on CT (p=0.04). CT features of pulmonary
fibrosis, especially traction bronchiectasis (HR 8.34, 95% CI 1.98-35.21) and
increased pulmonary artery (PA)/aorta ratio (HR 2.49, 95% CI 1.27-4.89) were
associated with worse survival, while ground-glass opacity (HR 0.31, 95% CI 0.12
0.79) was associated with improved survival. Survival association with imaging
was less pronounced after adjustment for gender, age and physiology score.
CONCLUSIONS: A substantial proportion of cHP cases have a non-HP-like appearance.
Ground-glass opacity, pulmonary fibrosis features and elevated PA/aorta ratio on
CT likely reflect varying degrees of disease severity in cHP and may inform
future clinical prediction models. KEY POINTS: * A substantial proportion of
subjects with chronic HP have a UIP-like pattern. * A UIP pattern in HP may be
potentiated by smoking. * A diagnosis of HP should not be excluded based solely
on CT appearance. * CT fibrosis and increased PA/aorta ratio signal worse
survival.
PMID- 28687911
TI - Incremental diagnostic value of targeted biopsy using mpMRI-TRUS fusion versus 14
fragments prostatic biopsy: a prospective controlled study.
AB - OBJECTIVES: To compare the incremental diagnostic value of targeted biopsy using
real-time multiparametric magnetic resonance imaging and transrectal ultrasound
(mpMRI-TRUS) fusion to conventional 14-cores biopsy. PATIENTS AND METHODS: Uni
institutional, institutional review board (IRB) approved prospective blinded
study comparing TRUS-guided random and targeted biopsy using mpMRI-TRUS fusion,
in 100 consecutive men. We included men with clinical-laboratorial suspicious for
prostate cancer and Likert score >= 3 mp-MRI. Patients previously diagnosed with
prostate cancer were excluded. All patients were submitted to 14-cores TRUS
guided biopsy (mpMRI data operator-blinded), followed by targeted biopsy using
mpMRI-TRUS fusion. RESULTS: There was an overall increase in cancer detection
rate, from 56% with random technique to 62% combining targeted biopsy using mpMRI
TRUS fusion; incremental diagnosis was even more relevant for clinically
significant lesions (Gleason >= 7), diagnosing 10% more clinically significant
lesions with fusion biopsy technique. Diagnosis upgrade occurred in 5 patients
that would have negative results in random biopsies and had clinically
significant tumours with the combined technique, and in 5 patients who had the
diagnosis of significant tumours after fusion biopsy and clinically insignificant
tumours in random biopsies(p=0.0010). CONCLUSIONS: Targeted biopsy using mpMRI
TRUS fusion has incremental diagnostic value in comparison to conventional random
biopsy, better detecting clinically significant prostate cancers. KEY POINTS: *
mpMRI-TRUS targeted biopsy increases overall cancer detection rate, but not
statistically significant. * mpMRI-TRUS targeted biopsy actually improves the
diagnosis of clinically significant PCa. * There was no evidence to acquire the
mpMRI-TRUS fusion cores alone.
PMID- 28687912
TI - Hyoscine butylbromide significantly decreases motion artefacts and allows better
delineation of anatomic structures in mp-MRI of the prostate.
AB - OBJECTIVES: To prospectively evaluate the effect of hyoscine butylbromide (HBB)
on visualisation of anatomical details and motion-related artefacts in mp-MRI of
the prostate at 3.0 Tesla. METHODS: One hundred and three consecutive patients
(65 +/- 10 years) were included in this trial, powered to demonstrate an
improvement of image quality after HBB administration, assessed on a 5-point
scale by two blinded readers. All patients received high-spatial resolution axial
T2-weighted TSE sequences at 3.0 T without spasmolytic agent, repeated after
application of 40 mg HBB and followed by routine mp-MRI. Secondary endpoints were
(1) susceptibility to side effects, (2) dependence of spasmolytic effect on
patients' weight, and (3) prostate volume. RESULTS: In 68% of patients, HBB
significantly improved the anatomic score (mean 3.4 +/- 0.9 before and 4.4 +/-
0.7 after HBB for both readers, p = <0.001). In 67%, HBB significantly enhanced
the artefact score (mean 3.2 +/- 1 before and 4.2 +/- 0.8 after HBB for reader 1,
p = <0.001; 3.2 +/- 1 and 4.1 +/- 0.8 for reader 2, p = <0.001). Subgroup
analysis revealed no statistically significant difference between patients with
different bodyweight or prostate volume. Inter-reader agreement was excellent (k
= 0.95-0.98). CONCLUSIONS: Hyoscine butylbromide significantly improves image
quality and reduces motion-related artefacts in mp-MRI of the prostate
independent of bodyweight or prostate volume. No side effects were reported. KEY
POINTS: * Hyoscine butylbromide (HBB) improved image quality in over 2/3 of
patients. * Severe artefacts were reduced after HBB in more than 20%. * The
number of non-diagnostic MRI was reduced to <1% after HBB. * HBB effect was
independent of bodyweight and prostate volume. * No side effects of HBB were
reported in this study population.
PMID- 28687913
TI - Risk stratification of gallbladder polyps larger than 10 mm using high-resolution
ultrasonography and texture analysis.
AB - OBJECTIVES: To assess important features for risk stratification of gallbladder
(GB) polyps >10 mm using high-resolution ultrasonography (HRUS) and texture
analysis. METHODS: We included 136 patients with GB polyps (>10 mm) who underwent
both HRUS and cholecystectomy (non-neoplastic, n = 58; adenomatous, n = 32; and
carcinoma, n = 46). Two radiologists retrospectively assessed HRUS findings and
texture analysis. Multivariate analysis was performed to identify significant
predictors for neoplastic polyps and carcinomas. RESULTS: Single polyp (OR, 3.680
3.856) and larger size (OR, 1.450-1.477) were independently associated with
neoplastic polyps (p < 0.05). In a single or polyp >14 mm, sensitivity for
differentiating neoplastic from non-neoplastic polyps was 92.3%. To differentiate
carcinoma from adenoma, sessile shape (OR, 9.485-41.257), larger size (OR, 1.267
1.303), higher skewness (OR, 6.382) and lower grey-level co-occurrence matrices
(GLCM) contrast (OR, 0.963) were significant predictors (p < 0.05). In a polyp
>22 mm or sessile, sensitivity for differentiating carcinomas from adenomas was
93.5-95.7%. If a polyp demonstrated at least one HRUS finding and at least one
texture feature, the specificity for diagnosing carcinoma was increased to 90.6
93.8%. CONCLUSION: In a GB polyp >10 mm, single and diameter >14 mm were useful
for predicting neoplastic polyps. In neoplastic polyps, sessile shape, diameter
>22 mm, higher skewness and lower GLCM contrast were useful for predicting
carcinoma. KEY POINTS: * Risk of neoplastic polyp is low in <14 mm and multiple
polyps * A sessile polyp or >22 mm has increased risk for GB carcinomas * Higher
skewness and lower GLCM contrast are predictors of GB carcinoma * HRUS is useful
for risk stratification of GB polyps >1 cm.
PMID- 28687914
TI - Longitudinal study of sodium MRI of articular cartilage in patients with knee
osteoarthritis: initial experience with 16-month follow-up.
AB - OBJECTIVES: To evaluate the potential of sodium MRI to detect changes over time
of apparent sodium concentration (ASC) in articular cartilage in patients with
knee osteoarthritis (OA). METHODS: The cartilage of 12 patients with knee OA were
scanned twice over a period of approximately 16 months with two sodium MRI
sequences at 7 T: without fluid suppression (radial 3D) and with fluid
suppression by adiabatic inversion recovery (IR). Changes between baseline and
follow-up of mean and standard deviation of ASC (in mM), and their rate of change
(in mM/day), were measured in the patellar, femorotibial medial and lateral
cartilage regions for each subject. A matched-pair Wilcoxon signed rank test was
used to assess significance of the changes. RESULTS: Changes in mean and in
standard deviation of ASC, and in their respective rate of change over time, were
only statistically different when data was acquired with the fluid-suppressed
sequence. A significant decrease (p = 0.001) of approximately 70 mM in mean ASC
was measured between the two IR scans. CONCLUSION: Quantitative sodium MRI with
fluid suppression by adiabatic IR at 7 T has the potential to detect a decrease
of ASC over time in articular cartilage of patients with knee osteoarthritis. KEY
POINTS: * Sodium MRI can detect apparent sodium concentration (ASC) in cartilage
* Longitudinal study: sodium MRI can detect changes in ASC over time * Potential
for follow-up studies of cartilage degradation in knee osteoarthritis.
PMID- 28687915
TI - Revised PROPELLER for T2-weighted imaging of the prostate at 3 Tesla: impact on
lesion detection and PI-RADS classification.
AB - PURPOSE: To evaluate revised PROPELLER (RevPROP) for T2-weighted imaging (T2WI)
of the prostate as a substitute for turbo spin echo (TSE). MATERIALS AND METHODS:
Three-Tesla MR images of 50 patients with 55 cancer-suspicious lesions were
prospectively evaluated. Findings were correlated with histopathology after MRI
guided biopsy. T2 RevPROP, T2 TSE, diffusion-weighted imaging, dynamic contrast
enhancement, and MR-spectroscopy were acquired. RevPROP was compared to TSE
concerning PI-RADS scores, lesion size, lesion signal-intensity, lesion contrast,
artefacts, and image quality. RESULTS: There were 41 carcinomas in 55 cancer
suspicious lesions. RevPROP detected 41 of 41 carcinomas (100%) and 54 of 55
lesions (98.2%). TSE detected 39 of 41 carcinomas (95.1%) and 51 of 55 lesions
(92.7%). RevPROP showed fewer artefacts and higher image quality (each p <
0.001). No differences were observed between single and overall PI-RADS scores
based on RevPROP or TSE (p = 0.106 and p = 0.107). Lesion size was not different
(p = 0.105). T2-signal intensity of lesions was higher and T2-contrast of lesions
was lower on RevPROP (each p < 0.001). CONCLUSION: For prostate cancer detection
RevPROP is superior to TSE with respect to motion robustness, image quality and
detection rates of lesions. Therefore, RevPROP might be used as a substitute for
T2WI. KEY POINTS: * Revised PROPELLER can be used as a substitute for T2-weighted
prostate imaging. * Revised PROPELLER detected more carcinomas and more
suspicious lesions than TSE. * Revised PROPELLER showed fewer artefacts and
better image quality compared to TSE. * There were no significant differences in
PI-RADS scores between revised PROPELLER and TSE. * The lower T2-contrast of
revised PROPELLER did not impair its diagnostic quality.
PMID- 28687916
TI - Amide proton transfer imaging for differentiation of benign and atypical
meningiomas.
AB - PURPOSE: To investigate the difference in amide proton transfer (APT)-weighted
signals between benign and atypical meningiomas and determine the value of APT
imaging for differentiating the two. METHODS: Fifty-seven patients with
pathologically diagnosed meningiomas (benign, 44; atypical, 13), who underwent
preoperative MRI with APT imaging between December 2014 and August 2016 were
included. We compared normalised magnetisation transfer ratio asymmetry (nMTR
asym ) values between benign and atypical meningiomas on APT-weighted images.
Conventional MRI features were qualitatively assessed. Both imaging features were
evaluated by multivariable logistic regression analysis. The discriminative value
of MRI with and without nMTR asym was evaluated. RESULTS: The nMTR asym of
atypical meningiomas was significantly greater than that of benign meningiomas
(2.46% vs. 1.67%; P < 0.001). In conventional MR images, benign and atypical
meningiomas exhibited significant differences in maximum tumour diameter, non
skull base location, and heterogeneous enhancement. On multivariable logistic
regression analysis, high nMTR asym was an independent predictor of atypical
meningiomas (adjusted OR, 11.227; P = 0.014). The diagnostic performance of MRI
improved with nMTR asym for predicting atypical meningiomas. CONCLUSION: Atypical
meningiomas exhibited significantly higher APT-weighted signal intensities than
benign meningiomas. The discriminative value of conventional MRI improved
significantly when combined with APT imaging for diagnosis of atypical
meningioma. KEY POINTS: * APT imaging is useful for differentiating between
atypical and benign meningiomas. * Atypical meningiomas exhibited high APT
weighted signal intensity than benign meningiomas. * The diagnostic performance
of MRI improved with nMTR asym for predicting atypical meningiomas.
PMID- 28687917
TI - The application of surgical procedure manager (SPM): first experience with FESS.
AB - In our hypothesis, the newly developed program SPM (surgical procedure manager)
will ensure successful standardization and efficiency of the FESS (functional
endoscopic sinus surgery) and therefore make a decisive contribution in terms of
economization and improvement of intraoperative quality. Between 27th March 2015
and 8th October 2015, data from 259 FESS procedures were collected using the SPM.
The study took place at the surgical desk, an operating room in the ACQUA clinic
in Leipzig, Germany. 233 FESS (90%) of the total FESS (n = 259, 100%) were
conducted entirely with SPM. 26 SPM terminations (10%) of 259 FESS remain, which
are classified as actual SPM terminations-when the surgeon intentionally stops
the SPM. The maximum time slot decreased clearly from 1 h 39 min (period A) to 1
h 10 min (period B). A time reduction can also be seen with the minimum duration
of 13.5 min compared to 11 min. The variability of the time slot also decreases
since the standard deviation is reduced by 4.5 min. On the basis of available
recordings it can be postulated that the application of SPM is suitable for
standardization for FESS. Standardization by means of SPM and minimal development
can be recognized over a period of time. The SPM makes it possible to transfer
the general advantages of mechanization on a concrete FESS and do not influence
the medical processes nor even restrict the medical freedom. The users are still
entirely free in the implementation of the respective procedure.
PMID- 28687918
TI - A retrospective study on facial nerve schwannomas: a disease with a high risk of
misdiagnosis and hearing loss.
AB - The objective is to increase awareness of facial nerve schwannomas (FNSs).
Clinical data from 32 cases with FNSs who received surgical treatment from 2005
to 2015 were reviewed retrospectively. The clinical data included age, sex,
presentations, duration, facial nerve function, temporal-bone high-resolution
computed tomography (CT) and magnetic resonance imaging (MRI) findings, surgical
approaches, and postoperative histopathological examination. 16 men and 16 women
were included, aged 7-69 years. The average age at diagnosis was approximately 44
years. The mean duration of disease was 65 months, and the mean tumor diameter
was 22.4 mm. A tendency of multisegment involvement was observed in 29 FNS cases.
Geniculate ganglion and tympanic segments were the most commonly involved
segments. Meanwhile, the incidence of misdiagnosis of this disease was 50%. We
observed that when FNSs involved the proximal portion of genicular ganglion, the
hearing function tended to be worse than when the FNSs only involved the
genicular ganglion and/or its distal portion (p < 0.05); in such cases, the
hearing loss tended to become more severe with a longer duration of the disorder
(p < 0.05). Multiple segment involvement is common in patients with FNS. We need
to be more aware of the hearing function when FNSs involve the proximal portion
of genicular ganglion. Misdiagnoses of FNS are common, and patients can be
misdiagnosed with Bell's palsy, otitis media, or other diseases. Image studies
should be conducted for differential diagnosis. Once the decision to perform
surgical resection was made, reconstruction of the facial nerve should be
considered.
PMID- 28687919
TI - Superior laryngeal nerve in thyroid surgery: anatomical identification and
monitoring.
AB - The aim of this study was to validate a procedure to identify and preserve the
external branch of the superior laryngeal nerve (EBSLN) during thyroid surgery.
The present study also aimed to analyze the EBSLN and the vagus nerve activities
after stimulation and demonstrate an operative association between all the
laryngeal muscles. Dissection of the cervical region was performed bilaterally in
four adult cadavers. In a second step, 144 patients undergoing total
thyroidectomy were included. Intraoperative stimulations of the cervical vagus
nerve and the EBSLN in the sternothyroid-laryngeal triangle were performed
bilaterally. Potentials in the thyroarytenoid muscle and the cricothyroid muscle
were registered on each side using the NIM3 Medtronic System. EBSLN was
identified according to Cernea's classification as type 1 in 62.5%, type 2a in
25%, and type 2b in 12.5% of cadaver's dissection. According to Friedman's
classification, 50% of EBSLN were classified type 1, 25% type 2 and 25% type 3.
The EBSLN was identified in 267 cases out of 288 peroperative dissections
(92.7%). Direct stimulation (1 mA) of this branch led to a recordable contraction
of the cricothyroid muscle with a mean latency of 1.42 +/- 0.66 ms on the right
side and 1.43 +/- 0.61 ms on the left side. The stimulation of the EBSLN also led
to a recordable contraction of the thyroarytenoid muscle in 211 cases (73.3%)
with the same latencies. A contraction of the cricothyroid muscle was also
recorded when the vagus nerve was stimulated in 219 cases (76.0%). The sole
visual identification of the EBSLN during thyroid surgery is not a reliable
method to prevent nerve injury. Direct stimulation of the EBSLN in the
sternothyroid-laryngeal triangle is a simple and rapid procedure to detect and
preserve the nerve during surgery. Functional associations between vagus nerve
and EBSLN in laryngeal muscles' contractions were also identified.
PMID- 28687920
TI - Complete genome sequence and phylogenetic analysis of Senecavirus A isolated in
Northeast China in 2016.
AB - Senecavirus A (SVA) is associated with vesicular disease in swine and the acute
death of neonatal piglets. Here, senecavirus A was isolated from a pig displaying
vesicular disease in Northeast China. The virus was designated as
SVA/HLJ/CHA/2016 and its full-length nucleotide sequence was determined and
analyzed in comparison with other known SVA strains. The complete genome sequence
of SVA/HLJ/CHA/2016 shares high nucleotide identities, of 93.8 to 99%, with
previously reported SVA full-length genomes. Phylogenetic analysis of both the
SVA full-length genomes and the VP1 genes revealed that the SVA/HLJ/CHA/2016
strain is closely related to the 2015 US strains, instead of other China
isolates. Our finding provides evidence that SVA infection of pigs has occurred
in Northeast China, and the importance of SVA surveillance in China should be
emphasized.
PMID- 28687921
TI - Phylogenetic analysis of Newcastle disease viruses from Bangladesh suggests
continuing evolution of genotype XIII.
AB - A total of 23 Newcastle disease virus (NDV) isolates from Bangladesh taken
between 2010 and 2012 were characterized on the basis of partial F gene
sequences. All the isolates belonged to genotype XIII of class II NDV but
segregated into three sub-clusters. One sub-cluster with 17 isolates aligned with
sub-genotype XIIIc. The other two sub-clusters were phylogenetically distinct
from the previously described sub-genotypes XIIIa, XIIIb and XIIIc and could be
candidates of new sub-genotypes; however, that needs to be validated through full
length F gene sequence data. The results of the present study suggest that
genotype XIII NDVs are under continuing evolution in Bangladesh.
PMID- 28687922
TI - Was Kaposi's sarcoma-associated herpesvirus introduced into China via the ancient
Silk Road? An evolutionary perspective.
AB - Kaposi's sarcoma-associated herpesvirus (KSHV) has become widely dispersed
worldwide since it was first reported in 1994, but the seroprevalence of KSHV
varies geographically. KSHV is relatively ubiquitous in Mediterranean areas and
the Xinjiang Uygur Autonomous Region, China. The origin of KSHV has long been
puzzling. In the present study, we collected and analysed 154 KSHV ORF-K1
sequences obtained from samples originating from Xinjiang, Italy, Greece, Iran
and southern Siberia using Bayesian evolutionary analysis in BEAST to test the
hypothesis that KSHV was introduced into Xinjiang via the ancient Silk Road.
According to the phylogenetic analysis, 72 sequences were subtype A and 82
subtype C, with C2 (n = 56) being the predominant subtype. The times to the most
recent common ancestors (tMRCAs) of KSHV were 29,872 years (95% highest
probability density [HPD], 26,851-32,760 years) for all analysed sequences and
2037 years (95% HPD, 1843-2229 years) for Xinjiang sequences in particular. The
tMRCA of Xinjiang KSHV was exactly matched with the time period of the ancient
Silk Road approximately two thousand years ago. This route began in Chang'an, the
capital of the Han dynasty of China, and crossed Central Asia, ending in the
Roman Empire. The evolution rate of KSHV was slow, with 3.44 * 10-6 substitutions
per site per year (95% HPD, 2.26 * 10-6 to 4.71 * 10-6), although 11 codons were
discovered to be under positive selection pressure. The geographic distances from
Italy to Iran and Xinjiang are more than 4000 and 7000 kilometres, respectively,
but no explicit relationship between genetic distance and geographic distance was
detected.
PMID- 28687924
TI - Definitive chemoradiation at high volume facilities is associated with improved
survival in glioblastoma.
AB - The standard of care for glioblastoma (GBM) is maximal safe resection followed by
concurrent chemoradiation (CRT). For several neoplasms, receipt of radiation
treatment at high-volume facilities has been associated with improved overall
survival (OS). The purpose of the present investigation was to determine if there
was an association between receipt of CRT for GBM at facilities with a higher
case volume and improved OS. The National Cancer Data Base was queried for
patients with GBM diagnosed between 2006 and 2012 that received full-course CRT.
Statistics included Kaplan-Meier analysis to compare OS between patients treated
facilities with the highest quartile volume (HVF) to those treated at lower case
volume facilities, multivariate logistic regression to determine factors
associated with treatment at a HVF, and Cox proportional hazards modeling to
determine variables associated with OS. A total of 4892 patients met the
specified criteria. Fourteen facilities (9.9%) treated the highest quartile
volume of patients, while 69 (48.6%) treated the lowest quartile volume (LVF) of
patients. Treatment at the HVF was associated with improved median OS (16.5 vs.
14.1 months, p < 0.001). Treatment at a LVF also independently predicted for
worse OS on multivariate analysis, along with age >70 years, and a resection
limited to a biopsy. This is the first study to demonstrate that treatment of GBM
with CRT at a HVF is associated with improved survival. Major goals of future
oncologic care should be to achieve greater standardization of quality of
treatment across facilities with different case volumes.
PMID- 28687923
TI - Lapatinib with whole brain radiotherapy in patients with brain metastases from
breast and non-small cell lung cancer: a phase II study of the Hellenic
Cooperative Oncology Group (HeCOG).
AB - Small molecules, mainly tyrosine kinase inhibitors, are currently used in various
malignancies. Lapatinib, a dual inhibitor of EGFR/HER2 tyrosine kinases, has
demonstrated effectiveness in brain metastases from HER2-overexpressing breast
cancer. It also appears to sensitize EGFR-expressing cell lines to radiation. To
evaluate the efficacy of lapatinib in combination with whole brain radiotherapy
(WBRT) in patients with brain metastases from non-small cell lung cancer (NSCLC)
and breast cancer, as assessed by volumetric analysis by MRI. 81 patients were
treated with WBRT (30 Gy in ten fractions) in combination with lapatinib 1250 mg
once daily, followed by lapatinib 1500 mg once daily for a total 6 weeks. 21
patients had primary breast cancer and 60 patients NSCLC. Pre- and post-treatment
MRI scans in a compact disk for central volumetric assessment were available for
43 patients. 27 patients (62.8%) achieved partial response, 15 patients (34.9%)
had stable disease and only one patient (2.3%) had disease progression. Response
was not associated to EGFR protein expression. All 81 patients were assessed for
safety. The large majority of the adverse events were mild. Eight deaths
occurred, four of which were considered related to the study drugs but there were
also other contributing factors. Nine cases of serious infections were observed
in eight patients, but they were also receiving dexamethasone. Lapatinib in
combination with WBRT in patients with brain metastases from breast cancer and
NSCLC is a feasible approach that can be further studied in larger clinical
trials.
PMID- 28687925
TI - Locus coeruleus.
AB - The locus coeruleus (LC) contains norepinephrine (NE)-synthesizing neurons that
send diffuse projections throughout the central nervous system. The LC-NE system
has a major role in arousal, attention and stress responses. In the brain, NE may
also contribute to long-term synaptic plasticity, pain modulation, motor control,
energy homeostasis and control of local blood flow. The LC is severely affected
in neurodegenerative disorders including Parkinson disease (PD). Involvement of
the noradrenergic neurons of the LC precedes that of dopaminergic neurons of the
substantia nigra pars compacta and has been increasingly recognized as a
potential major contributor to cognitive manifestations in early PD, particularly
impaired attention. Abnormal noradrenergic signaling may also potentially
contribute to motor manifestations of the disease.This makes the LC-NE system a
major contributor to the pathobiology and potential target for therapy of PD.
PMID- 28687926
TI - ATAT1 is essential for regulation of homeostasis-retaining cellular responses in
corticotrophs along hypothalamic-pituitary-adrenal axis.
AB - The production and secretion of adrenocorticotropin, a proopiomelanocortin (POMC)
derived hormone, by corticotrophs in the anterior pituitary, is regulated by
corticotrophin-releasing hormone (CRH) and glucocorticoids. We have previously
demonstrated that adrenalectomy induces alpha-tubulin N-acetyltransferase 1
(ATAT1) expression and alpha-tubulin acetylation in corticotrophs. However, the
regulatory mechanism of ATAT1 expression and the function of acetylated
microtubules in corticotrophs are unclear. Here, we analyze the effect of CRH or
dexamethasone on Atat1 expression in the mouse corticotroph AtT20 cell line. The
expression of Atat1 was increased by CRH and decreased by dexamethasone in AtT20
cells. We examined the effect of Atat1 knockdown on the expression of POMC
associated genes and the dexamethasone-induced nuclear translocation of
glucocorticoid receptor (GR) by real-time polymerase chain reaction and Western
blot analysis, respectively. Atat1 knockdown resulted in a significant increase
in the expression of ACTH-producing genes and decreased the dexamethasone-induced
nuclear translocation of GR accompanied with a reduction in alpha-tubulin
acetylation. Atat1 overexpression resulted in a significant increase in alpha
tubulin acetylation and the dexamethasone-induced nuclear translocation of GR.
These results suggest that the acetylated microtubules function as the rail-line
for the transportation of GR into the nucleus. We conclude that ATAT1 finely
tunes the cellular responses of corticotrophs to hormonal stimulation through an
intracellular feedback circuit.
PMID- 28687927
TI - The distribution of cholinergic neurons and their co-localization with FMRFamide,
in central and peripheral neurons of the spider Cupiennius salei.
AB - The spider Cupiennius salei is a well-established model for investigating
information processing in arthropod sensory systems. Immunohistochemistry has
shown that several neurotransmitters exist in the C. salei nervous system,
including GABA, glutamate, histamine, octopamine and FMRFamide, while
electrophysiology has found functional roles for some of these transmitters.
There is also evidence that acetylcholine (ACh) is present in some C. salei
neurons but information about the distribution of cholinergic neurons in spider
nervous systems is limited. Here, we identify C. salei genes that encode enzymes
essential for cholinergic transmission: choline ACh transferase (ChAT) and
vesicular ACh transporter (VAChT). We used in-situ hybridization with an mRNA
probe for C. salei ChAT gene to locate somata of cholinergic neurons in the
central nervous system and immunohistochemistry with antisera against ChAT and
VAChT to locate these proteins in cholinergic neurons. All three markers labeled
similar, mostly small neurons, plus a few mid-sized neurons, in most ganglia. In
the subesophageal ganglia, labeled neurons are putative efferent, motor or
interneurons but the largest motor and interneurons were unlabeled. Groups of
anti-ChAT labeled small neurons also connect the optic neuropils in the spider
protocerebrum. Differences in individual cell labeling intensities were common,
suggesting a range of ACh expression levels. Double-labeling found a
subpopulation of anti-VAChT-labeled central and mechanosensory neurons that were
also immunoreactive to antiserum against FMRFamide-like peptides. Our findings
suggest that ACh is an important neurotransmitter in the C. salei central and
peripheral nervous systems.
PMID- 28687929
TI - Periostin promotes ectopic osteogenesis of CTLA4-modified bone marrow mesenchymal
stem cells.
AB - The improved ectopic osteogenesis of cytotoxic T-lymphocyte-associated antigen 4
Ig-modified bone marrow mesenchymal stem cells (MSCs-CTLA4) has been demonstrated
but the mechanisms involved remain to be determined. The extracellular matrix
(ECM) has recently been reported to play a vital role in bone formation and
periostin (POSTN) has been suggested as a key member in constructing the ECM in
bone tissue. We found that POSTN expression in the MSCs-CTLA4 group is
significantly enhanced compared with that in the MSCs group, not only in tissue
engineered bone (TEB) with femur heterotopic transplantation in vivo but also
under the immune activation condition in vitro. This ectopic osteogenesis effect
is in accordance with POSTN expression. We also found that the soluble POSTN
treatment up-regulates osteogenic marker expression in MSCs, including runt
related transcription factor 2, collagen 1, osteocalcin, osterix, and alkaline
phosphatase and calcium nodule formation. These effects are diminished when the
soluble POSTN is neutralized. Our results demonstrate that POSTN promotes the
osteogenic differentiation of MSCs and that CTLA4 enhances the ectopic
osteogenesis of MSCs-CTLA4-based TEB, potentially by maintaining POSTN expression
in xenotransplantation.
PMID- 28687930
TI - Spatiotemporal expression patterns of clusterin in the mouse inner ear.
AB - Clusterin (CLU) is an extracellular chaperone protein that is implicated in
diverse physiological and pathophysiological cellular processes. CLU expression
is upregulated in response to cellular stress and under certain conditions, such
as neurodegenerative disease and cancer. CLU primarily functions as a chaperone
that exerts cytoprotective effects by removing cellular debris and misfolded
proteins and also acts as a signaling molecule that regulates pro-survival
pathways. Deafness is caused by genetic factors and various extrinsic insults,
including ototoxic drugs, exposure to loud sounds and aging. Considering its
cytoprotectivity, CLU may also mediate cellular defense mechanisms against
hearing loss due to cellular stresses. To understand the function of CLU in the
inner ear, we analyze CLU expression patterns in the mouse inner ear during
development and in the adult stage. Results of quantitative real-time polymerase
chain reaction analysis showed that Clu mRNA levels in the inner ear were
increased during embryogenesis and were constantly expressed in the adult.
Detailed spatial expression patterns of Clu both in the mRNA and protein levels
were analyzed throughout various developmental stages via in situ hybridization
and immunofluorescence staining. Clu expression was found in specific domains of
developing inner ear starting from the otocyst stage, mainly adjacent to the
prosensory domain of the cochlear epithelium. In the mature inner ear, Clu
expression was observed in Deiter's cells and pillar cells of the organ of Corti,
outer sulcus and in basal cells of the stria vascularis in the cochlea. These
specific spatiotemporal expression patterns suggest the possible roles of CLU in
inner ear development and in maintaining proper hearing function.
PMID- 28687931
TI - Differential cellular immune response of Galleria mellonella to Actinobacillus
pleuropneumoniae.
AB - In the present work, we have investigate the cellular immune response of Galleria
mellonella larvae against three strains of the gram-negative bacterium
Actinobacillus pleuropneumoniae: low-virulence (780), high-virulence (1022) and
the serotype 8 reference strain (R8). Prohemocytes, plasmatocytes, granulocytes,
oenocytoids and spherulocytes were distinguished according to their size and
morphology, their molecular markers and dye-staining properties and their role in
the immune response. Total hemocyte count, differential hemocyte count, lysosome
activity, autophagic response, cell viability and caspase-3 activation were
determined in circulating hemocytes of naive and infected larvae. The presence of
the autophagosome protein LC3 A/B within the circulating hemocytes of G.
mellonella was dependent on and related to the infecting A. pleuropneumoniae
strain and duration of infection. Hemocytes treated with the high-virulence
strain expressed higher levels of LC3 A/B, whereas treatment with the low
virulence strain induced lower expression levels of this protein in the cells.
Moreover, our results showed that apoptosis in circulating hemocytes of G.
mellonella larvae after exposure to virulent bacterial strains occurred
simultaneously with excessive cell death response induced by stress and
subsequent caspase-3 activation.
PMID- 28687928
TI - Combined effects of oscillating hydrostatic pressure, perfusion and encapsulation
in a novel bioreactor for enhancing extracellular matrix synthesis by bovine
chondrocytes.
AB - The influence of combined shear stress and oscillating hydrostatic pressure
(OHP), two forms of physical forces experienced by articular cartilage (AC) in
vivo, on chondrogenesis, is investigated in a unique bioreactor system. Our
system introduces a single reaction chamber design that does not require transfer
of constructs after seeding to a second chamber for applying the mechanical
forces, and, as such, biochemical and mechanical stimuli can be applied in
combination. The biochemical and mechanical properties of bovine articular
chondrocytes encapsulated in agarose scaffolds cultured in our bioreactors for 21
days are compared to cells statically cultured in agarose scaffolds in addition
to static micromass and pellet cultures. Our findings indicate that
glycosaminoglycan and collagen secretions were enhanced by at least 1.6-fold with
scaffold encapsulation, 5.9-fold when adding 0.02 Pa of shear stress and 7.6-fold
with simultaneous addition of 4 MPa of OHP when compared to micromass samples.
Furthermore, shear stress and OHP have chondroprotective effects as evidenced by
lower mRNA expression of beta1 integrin and collagen X to non-detectable levels
and an absence of collagen I upregulation as observed in micromass controls.
These collective results are further supported by better mechanical properties as
indicated by 1.6-19.8-fold increases in elastic moduli measured by atomic force
microscopy.
PMID- 28687932
TI - Spatial and temporal expression of Sox9 during murine incisor development.
AB - Mouse incisors are capable of continuously growing due to the renewal of dental
epithelium stem cells and mesenchymal stem cells residing at the proximal ends.
The transcription factor Sox9 plays important roles in maintaining the stem cells
of hair follicles, retinal progenitor cells and neural crest stem cells. Whether
Sox9 is involved during mouse incisor development is not reported yet. In this
study, we examined the expression pattern of Sox9 during mouse incisor
development by in situ hybridization and immunohistochemistry. Sox9 mRNA and
protein showed similar expression pattern from embryonic day (E) 13.5 to
postnatal (PN) day 10. At E13.5 and E14.5, Sox9 was strongly expressed in the
dental epithelium. At E16.5, Sox9 started to be detected in the mesenchymal cells
within the dental pulp, especially the dental pulp cells that adjacent to the
labial cervical loop. Similarly with E14.5, Sox9 was strongly detected in the
labial cervical loop, including the basal epithelium, the stellate reticulum and
the outer enamel epithelium from E16.5 to PN10. The mesenchyme adjacent to the
labial cervical loop also showed strong signal of Sox9. The spatiotemporal
expression of Sox9 suggested its possible involvement during mouse incisor
development.
PMID- 28687933
TI - Cellular zinc homeostasis modulates polarization of THP-1-derived macrophages.
AB - PURPOSE: Polarization of macrophages by environmental stimuli leads to the
characteristic of different phenotypes that exhibit distinct functions, ranging
in a continuous spectrum from pro-inflammatory M1 up to immunoregulatory and
wound-healing M2 macrophages. Diseases like cancer, allergic asthma or diabetes
are associated with an M1/M2 imbalance. Owing to the importance of the essential
trace element zinc for the immune system and its involvement in signal
transduction as a second messenger, we investigated the impact of zinc on M1 and
M2 polarization of macrophages in vitro. METHODS: A polarization model with human
THP-1 cells was established and validated with previously described markers using
quantitative real-time PCR, Western blot and flow cytometry. Intracellular free
Zn2+ was determined with FluoZin-3-AM. RESULTS: Whereas pSTAT1 and HLA-DR or
pSTAT6 and Dectin-1 distinguish between M1 and M2 macrophages, respectively, CD86
and CD206 failed. Depending on the used markers, both zinc supplementation in
physiological dose (50 uM) and zinc deficiency promote M1 polarization of THP-1
derived macrophages. Furthermore, zinc supplementation strongly inhibits M2
polarization. CONCLUSION: For the first time, we show a modulating effect of zinc
for the polarization of human macrophages. The strong inhibitory effect of zinc
supplementation on M2 polarization indicates a relevance regarding M2-dominated
diseases like allergic asthma or cancer. All in all, zinc achieves a great
potential for modulating macrophage polarization.
PMID- 28687934
TI - Co-administration of a konjac-based fibre blend and American ginseng (Panax
quinquefolius L.) on glycaemic control and serum lipids in type 2 diabetes: a
randomized controlled, cross-over clinical trial.
AB - PURPOSE: Use of polypharmacy in the treatment of diabetes is the norm;
nonetheless, optimal control is often not achieved. Konjac-glucomannan-based
fibre blend (KGB) and American ginseng (AG) have individually been shown to
improve glycaemia and CVD risk factors in type 2 diabetes. The aim of this study
was to determine whether co-administration of KGB and AG could improve diabetes
control beyond conventional treatment. METHOD: Thirty-nine participants with type
2 diabetes (6.5 > A1c < 8.4%) were enrolled between January 2002 and May 2003 at
the Risk Factor Modification Centre at St Michaels Hospital in a randomized,
placebo-controlled, crossover trial with each intervention lasting 12-weeks.
Medications, diet and lifestyle were kept constant. Interventions consisted of 6
g of fibre from KGB together with 3 g of AG (KGB and AG) or wheat bran-based,
fibre-matched control. Primary endpoint was the difference in HbA1c levels at
week 12. RESULTS: Thirty participants (18M:12F; age: 64 +/- 7 years; BMI: 28 +/-
5 kg/m2; HbA1c: 7.0 +/- 1.0%) completed the study, and consumed 5.5 and 4.9 g/day
of fibre from KGB and wheat bran control, respectively, and 2.7 g/day of AG. At
week 12, HbA1c levels were 0.31% lower on the KGB and AG compared to control (p =
0.011). Mean (+/-SEM) plasma lipids decreased on the KGB and AG vs control by 8.3
+/- 3.1% in LDL-C (p = 0.002), 7.5 +/- 2.4% in non-HDL-C (p = 0.013), 5.7 +/-
1.9% in total-C (p = 0.012), 4.1 +/- 2.1% in total-C:HDL-C ratio (p = 0.042), 9.0
+/- 2.3% in ApoB (p = 0.0005) and 14.6 +/- 4.2% in ApoB:ApoA1 ratio (p = 0.049).
CONCLUSIONS: Co-administration of KGB and AG increases the effectiveness of
conventional therapy through a moderate but clinically meaningful reduction in
HbA1c and lipid concentrations over 12 weeks in patients with type 2 diabetes.
CLINICAL TRIALS REGISTRATION: NCT02806349 ( https://clinicaltrials.gov/ ).
PMID- 28687935
TI - Update of Ablative Fractionated Lasers to Enhance Cutaneous Topical Drug
Delivery.
AB - Ablative fractional lasers (AFXL) enhance uptake of therapeutics and this newly
emerging field is called laser-assisted drug delivery (LAD). This new science has
emerged over the past decade and is finding its way into clinical practice. LAD
is poised to change how medicine delivers drugs. Topical and systemic application
of pharmaceutical agents for therapeutic effect is an integral part of medicine.
With topical therapy, the stratum corneum barrier of the skin impairs the ability
of drugs to enter the body. The purpose of LAD is to alter the stratum corneum,
epidermis, and dermis to facilitate increased penetration of a drug, device, or
cell to its respected target. AFXL represents an innovative, non-invasive
strategy to overcome the epidermal barrier. LAD employs three steps: (1)
breakdown of the skin barrier with a laser, (2) optional use a laser for a
therapeutic effect, (3) delivery of the medicine through laser channels to
further enhance the therapeutic effect. The advantages of using lasers for drug
delivery include the ease of accessibility, the non-invasive aspect, and its
effectiveness. By changing the laser settings, one may use LAD to have a drug
remain locally within the skin or to have systemic delivery. Many drugs are not
intended for use in the dermis and so it has yet to be determined which drugs are
appropriate for this technique. It appears this developing technology has the
ability to be a new delivery system for both localized and systemic delivery of
drugs, cells, and other molecules. With responsible development AFXL-assisted
drug delivery may become a new important part of medicine.
PMID- 28687936
TI - Prevalence of Lower Urinary Tract Symptoms in China, Taiwan, and South Korea:
Results from a Cross-Sectional, Population-Based Study.
AB - INTRODUCTION: Few population-based data are available evaluating the prevalence
of lower urinary tract symptoms (LUTS) in Asia. The objective of our study was to
determine LUTS prevalence in China, Taiwan, and South Korea using International
Continence Society (ICS) 2002 criteria. METHODS: An Internet-based self
administered survey among individuals aged at least 40 years with the ability to
use a computer and to read the local language. Survey questions included ICS
symptom definitions and the international prostate symptom score (IPSS). Data
analysis was based on descriptive statistics and post hoc significance testing.
RESULTS: There were 8284 participants, of whom 51% were women and 34% were aged
at least 60 years. LUTS prevalence was slightly higher in men than women (62.8%
vs. 59.6%; p = 0.004), increasing significantly with age (p = 0.001). All three
ICS symptom groups (voiding, storage, and post-micturition) were present in 35%
of individuals with LUTS. Symptoms with the highest overall prevalence were
nocturia, frequency, incomplete emptying, and terminal dribble. The most
bothersome symptoms were terminal dribble, nocturia, and urgency. According to
IPSS scores, 87% of participants had at least mild symptoms; 43% of those aged
over 60 years had moderate/severe symptoms. The percentage of participants with
any LUTS who had visited healthcare professionals because of urinary symptoms was
26%, rising to 45% amongst individuals with all three symptom groups (p = 0.001
vs. other ICS symptom groups). CONCLUSIONS: LUTS are highly prevalent in men and
women aged at least 40 years who participated in this study in China, Taiwan, and
South Korea and increases with increasing age. A minority of individuals with
LUTS seek healthcare and our results suggest an increased patient awareness of
LUTS is required. FUNDING: Astellas Pharma Singapore Pte. Ltd. TRIAL
REGISTRATION: ClinicalTrials.gov identifier, NCT02618421.
PMID- 28687937
TI - Short-Term Effects of a Combined Nutraceutical on Lipid Level, Fatty Liver
Biomarkers, Hemodynamic Parameters, and Estimated Cardiovascular Disease Risk: A
Double-Blind, Placebo-Controlled Randomized Clinical Trial.
AB - INTRODUCTION: There is a growing interest in nutraceuticals improving
cardiovascular risk factor levels and related organ damage. METHODS: This double
blind, placebo-controlled randomized clinical trial aims to compare the effect of
a combined nutraceutical containing red yeast rice (10 mg), phytosterols (800
mg), and L-tyrosol (5 mg) on lipid profile, blood pressure, endothelial function,
and arterial stiffness in a group of 60 patients with polygenic
hypercholesterolemia resistant to Mediterranean diet. RESULTS: After 8 weeks of
treatment, when compared to the placebo group, the active treated patients
experienced a more favorable percentage change in total cholesterol (-16.3% vs
9.9%, P < 0.001 always), LDL-C (-23.4% vs -13.2%, P < 0.001 always), and hepatic
steatosis index (-2.8%, P < 0.01 vs -1.8%, P < 0.05). Moreover, ALT (-27.7%, P <
0.001), AST (-13.8%, P = 0.004), and serum uric acid (-12.3%, P = 0.005) were
reduced by the tested nutraceutical compound both compared to randomization and
to placebo, which did not affect these parameters (P < 0.01 for all). Regarding
the hemodynamic parameters, there was a decrease of systolic blood pressure (
5.6%) with the active treatment not observed with placebo (P < 0.05 vs baseline
and placebo) and endothelial reactivity improved, too (-13.2%, P < 0.001 vs
baseline). Consequently, the estimated 10-year cardiovascular risk score improved
by 1.19% (SE 0.4%) (P = 0.01) in the nutraceutical-treated patients. CONCLUSION:
The tested nutraceutical association is able to improve the positive effects of a
Mediterranean diet on a large number of CV risk factors and consequently of the
estimated CV risk. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT02492464.
FUNDING: IBSA Farmaceutici.
PMID- 28687939
TI - Effects of different fat sources (saturated and unsaturated) on reproductive
performance and biological indices of ewes during flushing period.
AB - This study was conducted to evaluate the effect of feeding different sources of
fat during flushing period on the reproductive performance, lambing percent, and
twin numbers of Afshari ewes. A total of 84 ewes (mean weight 48 +/- 3 kg; age: 3
4 years) were divided into seven groups of 12 animals and received flushing
specific rations for 5 weeks. The control group just received a basic ration (non
flushing). Lipid sources were calcium salt of palm oil (CaP), pure palm oil (PO),
calcium salt of flaxseed (CaFL), calcium salt of sunflower oil (CaSF), flaxseed
oil (FLO), and sunflower oil (SFO). Estrous cycles were synchronized in all ewes
using 14-day CIDRs followed by 400-IU PMSG injection at the time of CIDR removal.
Fertility and lambing percent were higher in ewes fed with diets containing
calcium salts of flaxseed and SFO, as compared to other treatments. Total number
of lambs in flushing treatments was significantly higher than that in the control
group (p < 0.01). Serum cholesterol and progesterone levels were significantly
greater in omega-3 (CaFL) and omega-6 (CaSF) treatments relative to other
treatments (p < 0.01). It was concluded that supplementing the flushing diet with
calcium salts of fatty acids (CSFA) increased blood metabolites and hormones
related to reproductive performance; and improved fertility, lambing rate and
ewes of CaFL treatment have the highest number of lambs (16 lambs) between
different groups. Using saturated and unsaturated fatty acids, especially in
their CSFA forms during flushing period, could improve the reproduction problems
induced by progesterone deficiency, lack of durability of the fetus due to
hormonal instability, and abortion control factors.
PMID- 28687938
TI - A scoring system predicting the clinical course of CLPB defect based on the
foetal and neonatal presentation of 31 patients.
AB - Recently, CLPB deficiency has been shown to cause a genetic syndrome with
cataracts, neutropenia, and 3-methylglutaconic aciduria. Surprisingly, the
neurological presentation ranges from completely unaffected to patients with
virtual absence of development. Muscular hypo- and hypertonia, movement disorder
and progressive brain atrophy are frequently reported. We present the foetal,
peri- and neonatal features of 31 patients, of which five are previously
unreported, using a newly developed clinical severity scoring system rating the
clinical, metabolic, imaging and other findings weighted by the age of onset. Our
data are illustrated by foetal and neonatal videos. The patients were classified
as having a mild (n = 4), moderate (n = 13) or severe (n = 14) disease phenotype.
The most striking feature of the severe subtype was the neonatal absence of
voluntary movements in combination with ventilator dependency and
hyperexcitability. The foetal and neonatal presentation mirrored the course of
disease with respect to survival (current median age 17.5 years in the mild
group, median age of death 35 days in the severe group), severity and age of
onset of all findings evaluated. CLPB deficiency should be considered in neonates
with absence of voluntary movements, respiratory insufficiency and swallowing
problems, especially if associated with 3-methylglutaconic aciduria, neutropenia
and cataracts. Being an important differential diagnosis of hyperekplexia
(exaggerated startle responses), we advise performing urinary organic acid
analysis, blood cell counts and ophthalmological examination in these patients.
The neonatal presentation of CLPB deficiency predicts the course of disease in
later life, which is extremely important for counselling.
PMID- 28687940
TI - Changes in biochemical proxy indicators for nutritional stress resilience from
Boran and Nguni cows reared in dry arid rangeland.
AB - The objective of this study was to determine the changes in biochemical
indicators for nutritional stress from a herd of Boran and Nguni cows. A total of
40 cows (20 from each herd) were randomly selected for the study. The animals
were identified according to their parities as follows: parity 1 (n = 8), parity
2 (n = 16), parity 3 (n = 8) and parity 4 (n = 8). Serum chemistry levels of
glucose, total cholesterol, urea, creatinine, albumin, globulin, aspartate
aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase
(ALP), gamma glutylaminotransferase (GGT), leukocytes, erythrocytes, haemoglobin,
packed cell volume (PCV) and platelet counts were determined for 12 consecutive
months spanning across the wet and dry seasons. The Boran cows had different
creatinine concentration levels at different parities. The Boran cows in parity 1
had the highest (P < 0.05) concentration of creatinine 87.2 +/- 5.17 MUmol/L than
other cows in different parities within the herd. There were significant
differences in enzymes such as AST, ALP and ALT among the herd and parities.
Boran cows in parity 3 had the lowest (P < 0.05) AST concentration levels of 52.6
+/- 3.48 U/L, Nguni cows in parity 4 had the highest concentration of ALP of
161.3 +/- 8.10 U/L while Nguni cows in parity 1 had the highest concentration
level of ALT 55.1 +/- 1.56 U/L than all the cows within the same herd. The Nguni
herd had significantly higher (P < 0.05) levels of creatinine in both the wet
(97.8 +/- 3.27 MUmol/L) and dry seasons (108.7 +/- 3.29 MUmol/L) compared with
the Boran herd. Cows from the Nguni herd maintained significantly higher amount
of urea, creatinine, albumin and total protein in both the wet and dry seasons as
compared with cows from the Boran herd. Cows from the Nguni herd maintained
significantly higher amount of urea, creatinine, albumin and total protein in
both the wet and dry seasons as compared with those from the Boran herd.
PMID- 28687941
TI - Genetic parameters for tick counts across months for different tick species and
anatomical locations in South African Nguni cattle.
AB - The objective of the study was to characterise genetic parameters across months
for different tick species and anatomical locations in South African Nguni
cattle. Tick counts were conducted monthly, over a 2-year period, on 586 Nguni
cattle under natural infestation, from four herds located in different provinces
of South Africa. The counts were recorded for six species of ticks (Amblyomma
hebraeum, Rhipicephalus evertsi evertsi, Rhipicephalus decoleratus and microplus
(Boofilids), Rhipicephalus appendiculatus, Rhipicephalus simus and Hyalomma
marginatum) attached on eight anatomical locations on the animals and were summed
by species and anatomical location. Heritability estimates, phenotypic and
genetic correlations were estimated on a monthly basis using mixed linear models,
fitting univariate and bivariate sire models. Fixed effects considered were
location, sex, year and age as a covariate. Tick counts were higher in the hot
months, and A. hebraeum was the most dominant tick species. Heritability
estimates for tick count varied by month and trait and ranged from 0 to 0.89.
Genetic correlations were mostly positive, and low to high, with some negative
correlations with high standard error. Phenotypic correlations were low to
moderate. In general, high genetic correlations were observed between whole body
count and the anatomical location counts, suggesting that it may not be necessary
to conduct whole body counts. Counts from the belly and perineum appeared to be
the most suitable surrogate traits for whole body count. These findings provide
useful information for developing strategies for the practical implementation of
genetic selection, as a supplement to the traditional tick control measures.
PMID- 28687942
TI - Rare Duodenal Varix Coil Erosion Post TIPS Creation and Coil Embolization of
Mesenteric-Systemic Shunt.
PMID- 28687943
TI - Symptoms of Functional Intestinal Disorders Are Common in Patients with Celiac
Disease Following Transition to a Gluten-Free Diet.
AB - BACKGROUND: Celiac disease and functional intestinal disorders may overlap, yet
the natural history of functional symptoms in patients with celiac disease is
unknown. AIM: To investigate the prevalence of irritable bowel syndrome (IBS),
functional dyspepsia (FD), and functional bloating (FB) symptoms among patients
with celiac disease at diagnosis and during the first year of a gluten-free diet.
METHODS: Adults with a new diagnosis of celiac disease were surveyed at baseline,
6 months and 1 year using standardized measures for intestinal symptoms [Rome III
diagnostic questionnaire and celiac symptom index (CSI)] and gluten-free diet
adherence [gluten-free eating assessment tool (GF-EAT) and celiac diet adherence
test]. RESULTS: At diagnosis, two-thirds fulfilled Rome III diagnostic
questionnaire symptom criteria for IBS (52%), functional dyspepsia (27%), and/or
functional bloating (9%). One year post-diagnosis, there was high adherence to a
gluten-free diet as 93% reported gluten exposure less than once per month on the
GF-EAT and only 8% had ongoing celiac disease symptoms (CSI score >45). The rates
of those meeting IBS (22%) and functional dyspepsia (8%) symptom criteria both
decreased significantly on a gluten-free diet. The prevalence of functional
symptoms (any of IBS, FD or FB) at 1 year was 47%. CONCLUSIONS: Long-term follow
up of patients with celiac disease is necessary because many patients with celiac
disease who are adherent to a gluten-free diet have persistent gastrointestinal
symptoms.
PMID- 28687944
TI - Prolonged QTc indicates the clinical severity and poor prognosis in patients with
isolated left ventricular non-compaction.
AB - Isolated left ventricular non-compaction (LVNC) is a rare cardiomyopathy that
leads to severe clinical complications. This study is to investigate whether or
not prolonged QTc is a good indicator for evaluating the severity of fibrosis and
predicting the prognosis of LVNC, and if native T1 can be used to quantify the
fibrosis. 32 LVNC patients and 14 healthy controls with matched age and sex were
examined by CMR and ECG to acquire native T1, QTc interval, and ECG
abnormalities. 18 LVNC patients had normal QTc and 14 LVNC patients had prolonged
QTc. The mean native T1 value of the normal controls, normal QTc and prolonged
QTc patients was 1096.0 +/- 41.5, 1141.98 +/- 45.46, and 1182.67 +/- 42.02 ms,
respectively. One-way ANVOA showed significant differences in native T1 among
three groups (F = 14.9, p < 0.001). In LVNC patients, the QTc interval
significantly correlated with LVEF (p = 0.003, r = 0.51) and native T1 values (p
= 0.015, R = -0.47). This suggests that prolonged QTc is associated with more
severe compacted myocardial fibrosis, more cardiac dysfunction, and a poorer
prognosis in LVNC patients. Follow-up data showed significant differences in
adverse events between patients with normal QTc and patients with prolonged QTc
(p = 0.036). Prolonged QTc interval leads to more severe compacted myocardial
fibrosis, poorer cardiac dysfunction, and poorer prognosis in LVNC patients.
PMID- 28687945
TI - Extraction of Lactobacillus acidophilus CICC 6074 S-Layer Proteins and Their
Ability to Inhibit Enteropathogenic Escherichia coli.
AB - An adhesion-related protein of Lactobacillus acidophilus strain CICC 6074
involved in binding to Caco-2 cells and inhibiting Enteropathogenic Escherichia
coli (EPEC) was isolated and characterized. The S-layer protein was extracted
with 5M LiCl and the active fraction purified by gel filtration (G-75). The S
layer protein was visualized by SDS-PAGE and characterized by estimating the
relative molecular weight using mass spectra. The inhibitory effect of L.
acidophilus and its S-layer proteins on the ability of EPEC to adhere to cells
was explored by using a Caco-2 cell model. The results suggest that the S-layer
proteins of L. acidophilus are adhesive in nature and are involved in the
competitive exclusion of EPEC from Caco-2 cells.
PMID- 28687946
TI - Genome-Based Reclassification of Fusobacterium nucleatum Subspecies at the
Species Level.
AB - Fusobacterium nucleatum is classified as four subspecies, subsp. nucleatum,
polymorphum, vincentii, and animalis, based on DNA-DNA hybridization (DDH)
patterns, phenotypic characteristics, and/or multilocus sequence analysis (MLSA).
The gold standards for classification of bacterial species are DDH and 16S
ribosomal RNA gene (16S rDNA) sequence homology. The thresholds of DDH and 16S
rDNA similarity for delineation of bacterial species have been suggested to be
>70 and 98.65%, respectively. Average nucleotide identity (ANI) and genome-to
genome distance (GGD) analysis based on genome sequences were recently introduced
as a replacement for DDH to delineate bacterial species with ANI (95-96%) and GGD
(70%) threshold values. In a previous study, F. hwasookii was classified as a new
species based on MLSA and DDH results. 16S rDNA similarity between F. hwasookii
type strain and F. nucleatum subspecies type strains was higher than that between
F. nucleatum subspecies type strains. Therefore, it is possible that the four F.
nucleatum subspecies can be classified as Fusobacterium species. In this study,
we performed ANI and GGD analyses using the genome sequences of 36 F. nucleatum,
five F. hwasookii, and one Fusobacterium periodonticum strain to determine
whether the four F. nucleatum subspecies could be classified as species using
OrthoANI and ANI web-based softwares provided by ChunLab and Kostas lab,
respectively, and GGD calculator offered by German Collection of Microorganisms
and Cell Cultures. ANI values calculated from OrthoANI and ANI calculators
between the type strains of F. nucleatum subspecies ranged from 89.80 to 92.97
and from 90.40 to 91.90%, respectively. GGD values between the type strains of F.
nucleatum subspecies ranged from 42.3 to 46.0%. ANI and GGD values among strains
belonging to the same F. nucleatum subspecies, subsp. nucleatum, subsp.
polymorphum, subsp. vincentii, and subsp. animalis were >96 and >68.2%,
respectively. These results strongly suggest that F. nucleatum subsp. nucleatum,
subsp. polymorphum, subsp. vincentii, and subsp. animalis should be classified as
F. nucleatum, F. polymorphum, F. vincentii, and F. animalis, respectively.
PMID- 28687947
TI - Species of Tetrancistrum Goto & Kikuchi, 1917 (Monogenea: Dactylogyridae) from
the gills of the whitespotted rabbitfish, Siganus canaliculatus (Park)
(Perciformes: Siganidae) off Omani coasts, with a description of Tetrancistrum
labyrinthus n. sp.
AB - Tetrancistrum labyrinthus n. sp. is described from the gills of the marine
herbivorous fish Siganus canaliculatus (Park) found in the Western Indian Ocean
(Sea of Oman and Arabian Sea). Comparative morphological analyses of all
previously described species of Tetrancistrum Goto & Kikuchi, 1917 confirmed the
distinct status of T. labyrinthus n. sp. The new species closely resembles T.
suezicum Paperna, 1972 and T. oraminii Young, 1967 in the morphology of the male
copulatory organ. However, it can be distinguished by possessing a thin handle
like anterior basal flange and a compound accessory piece that is composed of a
tapering rod-shaped anterior part and a large cylindrical, elongated posterior
part. The new species can be further distinguished from other Tetrancistrum
species by its highly sclerotised and complex disc-shaped vaginal vestibule. This
is the first record of Tetrancistrum from the Sea of Oman and Arabian Sea, and
the fourth of nominal species of Tetrancistrum known to parasitise Siganus
canaliculatus (Park). In addition, T. indicum Paperna, 1972 is re-described here
with an updated locality record.
PMID- 28687948
TI - Role of Hepatobiliary Scintigraphy and Preoperative Liver Biopsy for Exclusion of
Biliary Atresia in Neonatal Cholestasis Syndrome.
AB - All diagnostic algorithms for Neonatal Cholestasis Syndrome (NCS) focus on
differentiating numerous medical causes from Biliary Atresia (BA). No
preoperative diagnostic algorithm has 100% diagnostic accuracy for BA and yet,
timely diagnosis is crucial to optimize surgical outcome. Markers for high index
of clinical suspicion for BA are: a "usually" well thriving infant with
conjugated hyperbilirubinemia, raised gamma glutamyl transpeptidase, persistently
"acholic" stools, firm hepatomegaly with dysmorphic, hypoplastic gall bladder. In
the presence of above 'red flag' signs, there has been much debate on diagnostic
accuracy of percutaneous liver biopsy (PLB) vs. hepatobiliary scintigraphy (HBS)
to substantiate or exclude BA. Recent guidelines suggest a shift towards PLB
(91.6% overall diagnostic accuracy) as the diagnostic cornerstone with key
differentiating feature being 'bile ductular proliferation'. HBS has a high
(98.7%) sensitivity but low specificity (37-74%) with an overall diagnostic
accuracy of 67% for BA. Severe hepatocellular disease without anatomic
obstruction would also have a non-excretory scan. Thus, while excretory HBS
excludes BA, non-excretion does not confirm BA. Hence, diagnostic algorithms
relying on non-excretory HBS as the primary standalone benchmark for surgical
exploration would be mired by a high negative laparotomy rate revealing a normal
peroperative cholangiogram (POC). However, an excretory HBS obviates need for
laparotomy in case of equivocal stool color or PLB. A POC continues to be the
ultimate gold standard. Hence, with high index of clinical suspicion but
equivocal ultrasonography or PLB and a non-excretory HBS, the baby should not be
denied a POC within time frame crucial for successful hepatoportoenterostomy.
PMID- 28687949
TI - Controversies of Sex Re-assignment in Genetic Males with Congenital Inadequacy of
the Penis.
AB - Sex assignment in 46XY genetic male children with congenital inadequacy of the
penis (CIP) is controversial. Traditionally, children with penile length less
than 2 cm at birth are considered unsuitable to be raised as males. They are
typically re-assigned to female-sex and feminizing genitoplasty is usually done
in infancy. However, the concept of cerebral androgen imprinting has caused
paradigm shift in the philosophy of sex re-assignment. Masculinization of the
brain, rather than length of the penis, is the modern criterion of sex re
assignment in CIP. This review summarizes the current understanding of the
complex issue. In 46XY children with CIP, male-sex assignment appears appropriate
in non-hormonal conditions such as idiopathic micropenis, aphallia and exstrophy.
Female-sex re-assignment appears acceptable in complete androgen insensitivity
(CAIS), while partial androgen insensitivity syndrome (PAIS) patients are highly
dissatisfied with the assignment of either sex. Children with 5-alpha reductase
deficiency are likely to have spontaneous penile lengthening at puberty. Hence,
they are better raised as males. Although female assignment is common in pure
gonadal dysgenesis, long-term results are not known to justify the decision.
PMID- 28687951
TI - Approach to "Upset Stomach".
AB - An "Upset stomach" is a common problem encountered by physicians involved in the
care of children. It includes, diarrhea, vomiting or abdominal pain. Though often
mild and self-limiting, at times there are uncommon life-threatening conditions
that require urgent care. It is important for primary physicians to recognize
"alarm signs" and make a referral to the specialist at the right time. At the
same time it is important to recognize what is normal and re-assure the
caregivers. A detailed history and a proper systemic examination are important at
presentation, looking for any "red flags". Investigations are seldom needed and
the treatment is symptomatic. In acute diarrhea, adequate hydration is the
cornerstone of management, which includes recognizing the degree of dehydration
and treating with oral rehydration solution and Zinc. Dysentery i.e., bloody
diarrhea needs treatment with antibiotics. In children with predominant vomiting
and abdominal pain, it is vital to make sure one is not dealing with a "surgical
"cause. If the child is not settling, a repeated examination is useful to look
for the persistence or evolution of abdominal signs. Vomiting does not localize
the problem to the gastro- intestinal (GI) tract and a complete systemic
examination is needed to rule out an extra GI cause.
PMID- 28687950
TI - Is Pre-operative Chemotherapy Desirable in all Patients of Wilms' Tumor?
AB - The timing and role of chemotherapy in the management of Wilms' tumor has long
been the matter of debate, with different groups showing equally comparable and
encouraging results. Over the last decade, however, both the ideol-ogies seem to
be converging and the attempt has been to identify groups benefitting with pre
operative chemotherapy, as well as those, where upfront resection should be
attempted. In this article authors intend to discuss pros and cons of both the
strategies and their applicability in a resource poor setting in developing
countries like India.
PMID- 28687952
TI - The Dynamics of Root Growth: A Geometric Model.
AB - A new model for macroscopic root growth based on a dynamical Riemannian geometry
is presented. Assuming that the thickness of the root is much less than its
length, the model is restricted to growth in one dimension (1D). We treat 1D
tissues as continuous, deformable, growing geometries for sizes larger than 1 mm.
The dynamics of the growing root are described by a set of coupled tensor
equations for the metric of the tissue and velocity field of material transport
in non-Euclidean space. These coupled equations represent a novel feedback
mechanism between growth and geometry. We compare 1D numerical simulations of
these tissue growth equations to two measures of root growth. First, sectional
growth along the simulated root shows an elongation zone common to many species
of plant roots. Second, the relative elemental growth rate calculated in silico
exhibits spatio-temporal dynamics recently characterized in high-resolution root
growth studies but which thus far lack a biological hypothesis to explain them.
In our model, these dynamics are a direct consequence of considering growth as
both a geometric reaction-diffusion process and expansion due to a distributed
source of new materials.
PMID- 28687953
TI - The effect of treadmill and overground walking on preferred walking speed and
gait kinematics in healthy, physically active older adults.
AB - PURPOSE: Preferred walking speed (PWS) represents a performance measure of
mobility in older individuals. PWS is usually assessed during overground (via a 2
40 m walkway) or treadmill walking in older adults. The aim of this study was to
compare the effect of treadmill and overground walking on preferred walking
speed, spatiotemporal parameters and foot kinematics in healthy, physically
active older and young adults after adequate treadmill familiarization. METHODS:
PWS and spatiotemporal parameters were assessed during overground (PWSO) and
treadmill (PWST) walking using two wearable inertial sensor systems and were
compared between 25 older (72.2 +/- 4.0, range 66-80 years) and 20 young (24.4 +/
2.1, range 20-30 years) adults. RESULTS: In the two groups, PWSO (older: 1.45 +/
0.17 m.s-1; young: 1.37 +/- 0.16 m.s-1) was significantly faster than PWST
(older: 1.31 +/- 0.15 m.s-1; young: 1.25 +/- 0.17 m.s-1; P < 0.001), with no
significant difference between the groups in either walking condition (P = 0.11).
The older adults walked with a significantly greater stride frequency (+8%; P <=
0.001) and lower plantarflexion angle (-5%; P <= 0.001) than the young
participants under both walking conditions. In both groups, treadmill walking was
characterized by significantly increased stance (+1%; P = 0.02) and double
support (+1%; P = 0.04) duration, as well as reduced swing duration (-1%; P =
0.02) and heel-strike pitch angle (-8%; P < 0.001). CONCLUSION: Our findings
showed that healthy and physically active older and young adults who were
adequately familiarized to the treadmill selected a slower PWS on the treadmill
than during overground walking with small "safety-related" gait kinematic
adaptations. Therefore, treadmill can be used for assessing PWS and gait
kinematics in physically active older adults.
PMID- 28687954
TI - Cortical voluntary activation testing methodology impacts central fatigue.
AB - PURPOSE: Currently, cortical voluntary activation (VATMS) is assessed by
superimposing transcranial magnetic stimulation (TMS) on a maximal voluntary
contraction (MVC), 75% MVC and 50% MVC, each contraction being interspersed with
5-10 s of relaxation. Here, we assessed whether this traditional approach (TRADI)
underestimates central fatigue due to this short recovery compared to a
continuous method (CONTI). METHODS: VATMS, motor-evoked potential (MEP), and
cortical silent period (CSP) of the vastus lateralis were determined in 12 young
healthy adults before and after a 2-min sustained MVC of knee extensors in two
randomly assigned sessions. In TRADI, evaluations comprised a 7-s rest between
the three contractions (100, 75, and 50% MVC) and evaluation following the 2-min
sustained MVC started after a minimal rest (3-4 s). In CONTI, evaluations were
performed with no rest allowed between the three levels of contraction, and
evaluation after the 2-min sustained MVC commenced without any rest. RESULTS: MVC
was equally depressed at the end of the 2 min in both conditions. Post 2-min
sustained MVC, VATMS change was greater in CONTI than in TRADI (-29 (15)% [-42,
17] vs. -9 (4)% [-13, -5], respectively, P < 0.001). Differences were also
observed between TRADI and CONTI for MEP and CSP immediately after the fatiguing
exercise. All differences between the two methods disappeared after 2 min of
recovery. CONCLUSION: After a 2-min sustained MVC, a few seconds of recovery
change the amount of measured VATMS and associated parameters of central fatigue.
The continuous method should be preferred to determine deficits in voluntary
activation.
PMID- 28687955
TI - Effects of recovery interval duration on the parameters of the critical power
model for incremental exercise.
AB - INTRODUCTION: We tested the linear critical power ([Formula: see text]) model for
discrete incremental ramp exercise implying recovery intervals at the end of each
step. METHODS: Seven subjects performed incremental (power increment 25 W)
stepwise ramps to subject's exhaustion, with recovery intervals at the end of
each step. Ramps' slopes (S) were 0.83, 0.42, 0.28, 0.21, and 0.08 W s-1;
recovery durations (t r) were 0 (continuous stepwise ramps), 60, and 180 s
(discontinuous stepwise ramps). We determined the energy store component (W'),
the peak power ([Formula: see text]), and [Formula: see text]. RESULTS: When t r
= 0 s, [Formula: see text] and W' were 187 +/- 26 W and 14.5 +/- 5.8 kJ,
respectively. When t r = 60 or 180 s, the model for ramp exercise provided
inconsistent [Formula: see text] values. A more general model, implying a
quadratic [Formula: see text] versus [Formula: see text] relationship, was
developed. This model yielded, for t r = 60 s, [Formula: see text] = 189 +/- 48 W
and W' = 18.6 +/- 17.8 kJ, and for t r = 180 s, [Formula: see text] = 190 +/- 34
W, and W' = 16.4 +/- 16.7 kJ. These [Formula: see text] and W' did not differ
from the corresponding values for t r = 0 s. Nevertheless, the overall amount of
energy sustaining work above [Formula: see text], due to energy store
reconstitution during recovery intervals, was higher the longer t r, whence
higher [Formula: see text] values. CONCLUSIONS: The linear [Formula: see text]
model for ramp exercise represents a particular case (for t r = 0 s) of a more
general model, accounting for energy resynthesis following oxygen deficit payment
during recovery.
PMID- 28687956
TI - CD163-positive cancer cells are potentially associated with high malignant
potential in clear cell renal cell carcinoma.
AB - CD163 is preferentially expressed by monocyte/macrophages; however, recent
studies using immunohistochemistry (IHC) have reported that some cancer cells
also express CD163. In the present IHC study, we investigated CD163 staining of
cancer cells and macrophages in clear cell renal cell carcinoma (ccRCC) tissues
and determined the relationship between cancer cell CD163 expression and clinical
prognosis in patients with ccRCC. IHC for CD163 was performed in ccRCC tissues
from 103 patients. CD163-positive cancer cells were detected in 35% of the
patients (36/103); however, the positive signals on cancer cells were
significantly lower than those on macrophages. CD163-positive cancer cells were
preferentially detected in patients with high T classification, and females, and
were significantly associated with shortened progression-free survival and a
lower overall survival ratio. Notably, a high intensity of CD163-positive
macrophage infiltration was detected in the CD163-positive cancer cell-high tumor
areas. Although CD163 mRNA was detected in cultured macrophages, no CD163 mRNA
was detected in two cultured RCC cell lines. The detailed mechanism by which a
positive signal is detected on cancer cells has not been clarified. Detection of
the CD163 antigen on cancer cells might be a useful marker for evaluating the
clinical course of patients with ccRCC.
PMID- 28687957
TI - Current Trends in Discharge Disposition and Post-discharge Care After Total Joint
Arthroplasty.
AB - PURPOSE OF REVIEW: The purpose of this manuscript is to review published
literature over the last 5 years to assess recent trends and influencing factors
regarding discharge disposition and post-discharge care following total joint
arthroplasty. We evaluated instruments proposed to predict a patient's discharge
disposition and summarize reports investigating the safety in sending more
patients home by reviewing complications and readmission rates. RECENT FINDINGS:
Current literature supports decreased length of hospital stay and increased
discharge to home with cost savings and stable readmission rates. Surgeons with
defined clinical pathways and those who shape patient expectations may more
effectively control costs than those without defined pathways. Further research
is needed analyzing best practices in care coordination, managing patient
expectations, and cost-effective analysis of home discharge while at the same
time ensuring patient outcomes are optimized following total joint arthroplasty.
PMID- 28687958
TI - Technology in Arthroplasty: Are We Improving Value?
AB - PURPOSE OF REVIEW: Total joint arthroplasty is regarded as a highly successful
procedure. Patient outcomes and implant longevity, however, are related to proper
alignment and position of the prostehses. In an attempt to reduce outliers and
improve accuracy and precision of component position, navigation and robotics
have been introduced. These technologies, however, come at a price. The goals of
this review are to evaluate these technologies in total joint arthroplasty and
determine if they add value. RECENT FINDINGS: Recent studies have demonstrated
that navigation and robotics in total joint arthroplasty can decrease outliers
while improving accuracy in component positioning. While some studies have
demonstrated improved patient reported outcomes, not all studies have shown this
to be true. Most studies cite increased cost of equipment and longer operating
room times as the major downsides of the technologies at present. Long-term
studies are just becoming available and are promising, as some studies have shown
decreased revision rates when navigation is used. Finally, there are relatively
few studies evaluating the direct cost and value of these technologies.
Navigation and robotics have been shown to improve component position in total
joint arthroplasty, which can improve patient outcomes and implant longevity.
These technologies offer a promising future for total joint arthroplasty.
PMID- 28687959
TI - Stem Cell Therapy for Fanconi Anemia.
AB - Stem cell therapy is the administration of stem cells to a patient to treat or
prevent a disease. Since stem cells possess the long-term self-renewal capacity
and provide daughter cells that differentiate into the specialized cells of each
tissue, stem cell therapy will theoretically improve the disease condition for
the lifetime of the patient. As the most widely used stem cell therapy, bone
marrow transplantation is the treatment of choice for many kinds of blood
disorders, including anemias, leukemias, lymphomas, and rare immunodeficiency
diseases. For the fatal genetic blood disorder Fanconi anemia, allogeneic bone
marrow transplantation has remained the only curative treatment. But the recent
advances in stem cell and gene therapy fields may provide promising opportunities
for an alternative or even better management of Fanconi anemia. Many of these new
ideas and opportunities are also useful for treating other blood diseases that
affect hematopoietic stem cells, such as sickle cell anemia, severe combined
immunodeficiencies, and beta-thalassemias. In this chapter, these advances along
with their challenges and limitations will be thoroughly discussed.
PMID- 28687960
TI - Dental Pulp Stem Cells and Neurogenesis.
AB - Recent advances in regenerative medicine and cell-based therapy are bringing
promising perspectives for the use of stem cells in clinical trials. Stem cells
are undifferentiated cells capable of multilineage differentiation and available
in numerous sources in the human body. Dental pulp constitutes an attractive
source of these cells since collecting mesenchymal stem cells from this site is a
noninvasive procedure which can be done following a common surgical extraction of
supernumerary or wisdom teeth. Thus tissue sacrifice is very low and several
cytotypes can be obtained owing to these cells' multipotency, in addition to the
fact that they can be cryopreserved and stored for long periods. Mesenchymal stem
cells have high proliferation rates making them favorable for clinical
application. These multipotent cells present in a biological waste constitute an
appropriate support in the management of many neurological disorders. After a
brief overview on the different types of dental stem cells, this chapter will
focus on the characteristics of dental pulp stem cells, their handling and
applications in neural tissue engineering, as well as neural induction protocols
leading to their potential therapeutic use in the management of neurological
diseases.
PMID- 28687961
TI - Allogeneic Adipose-Derived Mesenchymal Stem Cell Transplantation Enhances the
Expression of Angiogenic Factors in a Mouse Acute Hindlimb Ischemic Model.
AB - Cell migration and molecular mechanisms during healing of damaged vascular or
muscle tissues are emerging fields of interest worldwide. The study herein
focuses on evaluating the role of allogenic adipose-derived mesenchymal stem
cells (ADMSCs) in restoring damaged tissues. Using a hindlimb ischemic mouse
model, ADMSC-mediated induction of cell migration and gene expression related to
myocyte regeneration and angiogenesis were evaluated. ADMSCs were labeled with
GFP (ADMSC-GFP). The proximal end of the femoral blood vessel of mice (over 6
months of age) are ligated at two positions then cut between the two ties.
Hindlimb ischemic mice were randomly divided into two groups: Group I (n = 30)
which was injected with PBS (100 MUL) and Group II (n = 30) which was
transplanted with ADMSC-GFP (106 cells/100 MUL PBS) at the rectus femoris muscle.
The migration of ADMSC-GFP in hindlimb was analyzed by UV-Vis system. The
expression of genes related to angiogenesis and muscle tissue repair was
quantified by real-time RT-PCR. The results showed that ADMSCs existed in the
grafted hindlimb for 7 days. Grafted cells migrated to other damaged areas such
as thigh and heel. In both groups the ischemic hindlimb showed an increased
expression of several angiogenic genes, including Flt-1, Flk-1, and Ang-2. In
particular, the expression of Ang-2 and myogenic-related gene MyoD was
significantly increased in the ADMSC-treated group compared to the PBS-treated
(control) group; the expression increased at day 28 compared to day 3. The other
factors, such as VE-Cadherin, HGF, CD31, Myf5, and TGF-beta, were also more
highly expressed in the ADMSC-treated group than in the control group. Thus,
grafted ADMSCs were able to migrate to other areas in the injured hindlimb,
persist for approximately 7 days, and have a significantly positive impact on
stimulating expression of myogenic- and angiogenesis-related genes.
PMID- 28687962
TI - The impact of goal-oriented task design on neurofeedback learning for brain
computer interface control.
AB - Neurofeedback training teaches individuals to modulate brain activity by
providing real-time feedback and can be used for brain-computer interface
control. The present study aimed to optimize training by maximizing engagement
through goal-oriented task design. Participants were shown either a visual
display or a robot, where each was manipulated using motor imagery (MI)-related
electroencephalography signals. Those with the robot were instructed to quickly
navigate grid spaces, as the potential for goal-oriented design to strengthen
learning was central to our investigation. Both groups were hypothesized to show
increased magnitude of these signals across 10 sessions, with the greatest gains
being seen in those navigating the robot due to increased engagement.
Participants demonstrated the predicted increase in magnitude, with no
differentiation between hemispheres. Participants navigating the robot showed
stronger left-hand MI increases than those with the computer display. This is
likely due to success being reliant on maintaining strong MI-related signals.
While older participants showed stronger signals in early sessions, this trend
later reversed, suggesting greater natural proficiency but reduced flexibility.
These results demonstrate capacity for modulating neurofeedback using MI over a
series of training sessions, using tasks of varied design. Importantly, the more
goal-oriented robot control task resulted in greater improvements.
PMID- 28687963
TI - SPARC gene variants predict clinical outcome in locally advanced and metastatic
pancreatic cancer patients.
AB - Secreted protein acidic and rich in cysteine (SPARC) is a glycoprotein of the
extracellular matrix whose expression can be altered in malignant pancreatic
cells and in the adjacent stromal fibroblasts. We evaluated the possible role of
SPARC gene variants as prognostic markers for locally advanced and metastatic
pancreatic cancer. We analyzed eight tagging single-nucleotide polymorphisms
(TagSNPs) in the SPARC gene in 74 patients with pancreatic ductal adenocarcinoma
treated with chemotherapy alone or combined with radiotherapy. TagSNPs were
chosen using the HapMap genome browser and Haploview software 4.2 based on two
predefined criteria: (1) coefficient cutoff of 0.80 and (2) minor allele
frequency (MAF) >= 0.10. Univariate analyses revealed significant associations
between four SNPs (rs17718347, rs2347128, rs3210714, and rs967527) and PFS. The
rs3210714 genetic variant was also associated with OS. In the multivariate
analyses, rs17718347 (HR 0.4; 95% CI 0.2-0.8; p = 0.013) and rs2347128 (HR 0.5;
95% CI 0.3-0.9; p = 0.049) remained statistically associated with PFS. In
addition, patients harboring the T-A-G haplotype (rs17718347, rs1978707,
rs2347128) had a better PFS (p = 0.002). Our findings suggest that SPARC
polymorphisms may be useful in predicting outcome in patients with locally
advanced and metastatic pancreatic cancer.
PMID- 28687964
TI - Predictors of the usefulness of duloxetine for chemotherapy-induced peripheral
neuropathy.
AB - Duloxetine is an effective therapeutic agent for chemotherapy-induced peripheral
neuropathy (CIPN). However, predictors of duloxetine response have not been
adequately explored. Therefore, this retrospective study was performed to
identify predictive factors of duloxetine response in CIPN patients to guide
future strategies to improve the quality of life of patients undergoing
chemotherapy. The participants were 74 cancer patients who were given duloxetine
for relief of CIPN at our institute between October 2010 and January 2016.
Variables were extracted from clinical records for regression analysis of factors
related to relief of CIPN. We evaluated the effect of duloxetine 2 weeks after
administration. Groups were categorized according to degree of improvement: poor,
effective, and very effective. Multivariate ordered logistic regression analysis
was performed to identify predictive factors for the usefulness of duloxetine.
Threshold measures were examined using a receiver operating characteristic
analysis (ROC) curve. Body height [odds ratio (OR) 0.943, 95% confidence interval
(CI) 0.889-0.997; P = 0.0387], history of docetaxel use (OR 0.084, 95% Cl 0.009
0.814; P = 0.0325), and site of symptom (upper limb) (OR 3.848, 95% Cl 1.072
13.807; P = 0.0387) were significant factors related to the effect of duloxetine.
ROC curve analysis of the poor effect group indicated a threshold for body height
of >171.4 cm (area under the curve [AUC] = 0.61). In conclusion, body height
(low), history of docetaxel use (less), and site of symptom (upper limb) were
shown to be predictive factors for the usefulness of duloxetine for CIPN in
patients undergoing chemotherapy.
PMID- 28687965
TI - What is This Image? 2017: Image 1 Result : Incidental detection of RIB fractures
with Tc-99m pyrophosphate scanning.
PMID- 28687966
TI - Time-frame sampling for 82Rb PET flow quantification: Towards standardization of
clinical protocols.
PMID- 28687967
TI - Relationship of non-invasive quantification of myocardial blood flow to
arrhythmic events in patients with implantable cardiac defibrillators.
AB - BACKGROUND: Ischemia contributes to arrhythmogenesis though its role is
incompletely understood. Abnormal myocardial perfusion measured by PET imaging
may predict ventricular arrhythmias (VAs) in a high-risk population. METHODS:
Patients with implantable cardiac defibrillators who had undergone rubidium-82
cardiac PET imaging were identified. Patients were stratified by median MBF and
MFR values for analysis. The Cox proportional hazards model was used to assess
the impact of myocardial perfusion on survival free of VT independent of critical
covariates. RESULTS: A total of 159 patients (124 (78%) males, median age 65.9
years, IQR [56.76-72.63]) were followed for 1.43 years IQR [0.83-2.21]. VA
occurred in 29 patients (23.7%). After adjustment for ejection fraction, age, and
sex, impaired stress MBF was associated with an increased risk of VA (adjusted HR
per ml/min/g 1.52, 95% CI (1.01-2.31), P = 0.04). Summed rest and stress scores
were not predictive of VA. Among patients with severe LV dysfunction, stress MBF
remained an independent predictor of VA (adjusted HR per 1 ml/min/g HR 1.69, 95%
CI (1.03-11.36), P = 0.03), while residual EF, summed rest, and summed stress
scores were not (P > 0.05). CONCLUSIONS: Impaired stress myocardial blood flow
was associated with less survival free of ventricular arrhythmias.
PMID- 28687968
TI - Associations between obstructive sleep apnea severity and endoscopically proven
gastroesophageal reflux disease.
AB - PURPOSE: Obstructive sleep apnea (OSA) is believed to be an important risk factor
for gastroesophageal reflux disease (GERD). However, the association between OSA
and GERD is not straightforward and has been incompletely characterized. The aim
of this study was to assess the relationship between OSA and GERD by performing
both polysomnography (PSG) and esophagogastroduodenoscopy (EGD). METHODS: The
enrolled patients underwent both PSG and EGD from October 2003 to July 2015 at
Seoul National University Bundang Hospital. All patients were checked for the
presence of mucosal injury in the EGD findings and divided into a no-GERD group
and a GERD group according to the Los Angeles (LA) classification. In addition,
the GERD symptoms of heartburn, acid regurgitation, and reflux-related cough were
recorded. RESULTS: A total of 216 patients were enrolled. Ninety-nine patients
(45.8%) were in the GERD group, 68 (31.5%) were the minimal-change GERD group,
and 49 (22.7%) were in the GERD LA-A/B group. The OSA-related findings were worse
in the GERD LA-A/B group than in the no-GERD group: the apnea-hypopnea index was
33.6 +/- 25.5 versus 22.0 +/- 17.2 (p = 0.01), the longest apnea duration was
50.7 +/- 24.0 versus 41.6 +/- 23.3 s (p = 0.03), the lowest oxygen saturation was
80.2 +/- 7.9 versus 83.2 +/- 7.5% (p = 0.02), and the oxygen desaturation index
was 25.1 +/- 22.4 versus 16.1 +/- 15.5 (p = 0.01), respectively. Sleep efficiency
was significantly worse in patients with GERD symptoms (81.2 +/- 10.8%) than in
those without GERD symptoms (85.1 +/- 11.4%) (p = 0.03). CONCLUSIONS:
Endoscopically proven GERD was associated with more severe OSA. GERD symptoms
were also associated with deteriorated sleep quality.
PMID- 28687969
TI - Impact of Zika virus for infertility specialists: current literature, guidelines,
and resources.
AB - In the past 2 years, Zika virus has emerged from obscurity onto the world stage
traversing and transcending clinical specialties, basic science disciplines, and
public health efforts. The spread of Zika virus has serious implications for the
specialty of reproductive endocrinology and infertility. Our patients, practices,
and labs-worldwide and specifically in the USA-have been impacted by this
teratogenic, sexually transmitted, largely asymptomatic virus. While the World
Health Organization's Public Emergency of International Concern designation has
lapsed as major epidemics have subsided and understanding of risks is in part
clarified, the acute and long-term threat to pregnant patients is not over. The
risk of wider spread in the USA is not insignificant, the subtler and long
ranging consequences beyond microcephaly are not fully known, large geographic
areas of risk still contain naive populations, and whether Zika will continue to
be an intermittent risk in endemic areas is uncertain. Staying up to date with
the burgeoning research on Zika virus is an important objective for the
infertility specialist. Here, we review in detail the most relevant recent
developments, discuss applicable guidelines, and propose strategies for
contributing to a reduction in the risk and burden of Zika virus.
PMID- 28687970
TI - Association of genetic variations in RTN4 3'-UTR with risk for clear cell renal
cell carcinoma.
AB - Nogo proteins play an important role in the apoptosis of cells, especially in
tumor cells. The present study was conducted to evaluate whether the TATC
(rs71682980) and CAA (rs34917480) insertion/deletion polymorphisms of RTN4 3'-UTR
are associated with clear cell renal cell carcinoma (ccRCC). These two
polymorphisms were genotyped in 308 ccRCC patients and 466 healthy controls by
polymerase chain reaction polyacrylamide gel electrophoresis (PCR-PAGE).
Significantly reduced ccRCC risk was observed to be associated with the
TATCins/ins genotype carriers (Versus TATCdel/del: adjusted OR 0.53, 95% CI 0.32
0.87, P = 0.022; Versus TATCdel/del-del/ins: adjusted OR 0.57, 95% CI 0.36-0.92,
P = 0.017). After performing stratification analysis, the frequency of
TATCins/ins genotype was observed to be significantly higher in patients with N0
compared the patients with N1 (P = 0.003). The present study provide evidence for
the first time that the TATC insertion/deletion polymorphism in RTN4 3'-UTR may
contributes to ccRCC risk in Chinese Han population.
PMID- 28687971
TI - The spectrum of genetic variants in hereditary pancreatic cancer includes Fanconi
anemia genes.
AB - Approximately 5-10% of all pancreatic cancer patients carry a predisposing
mutation in a known susceptibility gene. Since >90% of patients present with late
stage disease, it is crucial to identify high risk individuals who may be
amenable to early detection or other prevention. To explore the spectrum of
hereditary pancreatic cancer susceptibility, we evaluated germline DNA from
pancreatic cancer participants (n = 53) from a large hereditary cancer registry.
For those without a known predisposition mutation gene (n = 49), germline next
generation sequencing was completed using targeted capture for 706 candidate
genes. We identified 16 of 53 participants (30%) with a pathogenic (P) or likely
pathogenic (LP) variant that may be related to their hereditary pancreatic cancer
predisposition; seven had mutations in genes associated with well-known cancer
syndromes (13%) [ATM (2), BRCA2 (3), MSH2 (1), MSH6 (1)]. Many had mutations in
Fanconi anemia complex genes [BRCA2 (3 participants), FANCF, FANCM]. Eight
participants had rare protein truncating variants of uncertain significance with
no other P or LP variants. Earlier age of pancreatic cancer diagnosis (57.5 vs
64.8 years) was indicative of possessing a P or LP variant, as was cancer family
history (p values <0.0001). Our multigene panel approach for identifying known
cancer predisposing genetic susceptibility in those at risk for hereditary
pancreatic cancer may have direct applicability to clinical practice in cases
with mutations in actionable genes. Future pancreatic cancer predisposition
studies should include evaluation of the Fanconi anemia genes.
PMID- 28687972
TI - Hypersomnia hiding a bipolar disorder.
PMID- 28687973
TI - Effect of exercise therapy on quality of life of patients with multiple sclerosis
in Iran: a systematic review and meta-analysis.
AB - Multiple sclerosis (MS) is a chronic and progressive disease charachterized by
disabilities which adversely affect individuals' quality of life (QOL). In the
present study, the effect size of exercise therapy on patients' QOL in both
physical and mental dimensions were investigated and the moderator effect of a
number of selected theoretical and significant practical variables were assessed.
Relevant studies, published before July 2015, were identified by searching
PubMed, Scopus, Google scholar, and Persian medical databases including
IranMedex, Irandoc, Magiran, Scientific Information Database (SID), and Medlib.
Supplementary searches were also performed manually by reviewing the reference
lists of the relevant articles. Next, using a randomized controlled trial (RCT)
design, English and/or Persian-language articles conducted in Iran and evaluating
the effect of exercise therapy on physical and/or mental aspects of QOL of MS
patients were pooled. Afterwards, two competent reviewers in the field extracted
the required data and rated the quality of the studies. Twenty-one journal
articles were identified and reviewed, but only 13 of them contained the as much
data as required to serve the purpose of the study. The mean effect size of
exercise therapy on mental, physical, and overall QOL of the patients were 1.021
(95%CI 0.712-1.331, P < .001), 1.040 (95%CI 0.730-1.349, P < .001), and 0.846
(95%CI 0.508-1.184, P < .001), respectively. Based on the investigated Iranian
studies, there is strong evidence confirming the effect of exercise therapy on
QOL of patients with MS; there, however, exists a need for more studies to
identify and establish effective exercise programs due to the heterogeneity of
the studies conducted in this area.
PMID- 28687974
TI - SYNE1 related cerebellar ataxia presents with variable phenotypes in a
consanguineous family from Turkey.
AB - SYNE1 related autosomal recessive cerebellar ataxia type 1 (ARCA1) is a late
onset cerebellar ataxia with slow progression originally demonstrated in French
Canadian populations of Quebec, Canada. Nevertheless, recent studies on SYNE1
ataxia have conveyed the condition from a geographically limited pure cerebellar
recessive ataxia to a complex multisystem phenotype that is relatively common on
the global scale. To determine the underlying genetic cause of the ataxia
phenotype in a consanguineous family from Turkey presenting with very slow
progressive cerebellar symptoms including dysarthria, dysmetria, and gait ataxia,
we performed SNP-based linkage analysis in the family along with whole exome
sequencing (WES) in two affected siblings. We identified a homozygous variant in
SYNE1 (NM_033071.3: c.13086delC; p.His4362GlnfsX2) in all four affected siblings.
This variant presented herein has originally been associated with only pure
ataxia in a single case. We thus present segregation and phenotypic
manifestations of this variant in four affected family members and further extend
the pure ataxia phenotype with upper motor neuron involvement and peripheral
neuropathy. Our findings in turn established a precise molecular diagnosis in
this family, demonstrating the use of WES combined with linkage analysis in
families as a powerful tool for establishing a quick and precise genetic
diagnosis of complex neurological phenotypes.
PMID- 28687975
TI - Prevalence and drug resistance characteristics of carbapenem-resistant
Enterobacteriaceae in Hangzhou, China.
AB - With the abuse of antimicrobial agents in developing countries, increasing number
of carbapenem-resistant Enterobacteriaceae (CRE) attracted considerable public
concern. A retrospective study was conducted based on 242 CRE strains from a
tertiary hospital in Hangzhou, China to investigate prevalence and drug
resistance characteristics of CRE in southeast China. Bacterial species were
identified. Antimicrobial susceptibility was examined by broth microdilution
method or epsilometer test. Resistant beta-lactamase genes were identified by
polymerase chain reaction and sequencing. Genotypes were investigated by
phylogenetic analysis. Klebsiella pneumoniae and Escherichia coli were the most
prevalent types of species, with occurrence in 71.9% and 21.9% of the strains,
respectively. All strains exhibited high resistance (> 70%) against beta-lactam
antibiotics, ciprofloxacin, trimethoprim-sulfamethoxazole, and nitrofurantoin but
exhibited low resistance against tigecycline (0.8%) and minocycline (8.3%). A
total of 123 strains harbored more than two kinds of beta-lactamase genes. blaKPC
2, blaSHV-11, blaTEM-1, and blaCTX-M-14 were the predominant genotypes, with
detection rates of 60.3%, 61.6%, 43.4%, and 16.5%, respectively, and were highly
identical with reference sequences in different countries, indicating potential
horizontal dissemination. IMP-4 was the most frequent class B metallo-lactamases
in this study. In conclusion, continuous surveillance and effective prevention
should be emphasized to reduce spread of CRE.
PMID- 28687976
TI - Annexin A2-S100A10 heterotetramer is upregulated by PML/RARalpha fusion protein
and promotes plasminogen-dependent fibrinolysis and matrix invasion in acute
promyelocytic leukemia.
AB - Aberrant expression of annexin A2-S100A10 heterotetramer (AIIt) associated with
PML/RARalpha fusion protein causes lethal hyperfibrinolysis in acute
promyelocytic leukemia (APL), but the mechanism is unclear. To facilitate the
investigation of regulatory association between ANXA2 and promyelocytic
leukemia/retinoic acid receptor a (PML/RARalpha) fusion protein, this work was
performed to determine the transcription start site of ANXA2 promoter with rapid
amplification of 5'-cDNA ends analysis. Zinc-induced U937/PR9 cells expressed
PML/RARalpha fusion protein, and resultant increases in ANXA2 transcripts and
translational expressions of both ANXA2 and S100A10, while S100A10 transcripts
remained constitutive. The transactivation of ANXA2 promoter by PML/RARalpha
fusion protein was 3.29 +/- 0.13 fold higher than that by control pSG5 vector or
wild-type RARalpha. The overexpression of ANXA2 in U937 transfected with full
length ANXA2 cDNA was associated with increased S100A10 subunit, although S100A10
transcripts remained constitutive. The tPA-dependent initial rate of plasmin
generation (IRPG) in zinc-treated U937/PR9 increased by 2.13-fold, and cell
invasiveness increased by 27.6%. Antibodies against ANXA2, S100A10, or
combination of both all remarkably inhibited the IRPG and invasiveness in
U937/PR9 and NB4. Treatment of zinc-induced U937/PR9 or circulating APL blasts
with all-trans retinoic acid (ATRA) significantly reduced cell surface ANXA2 and
S100A10 and associated reductions in IRPG and invasiveness. Thus, PML/RARalpha
fusion protein transactivated the ANXA2 promoter to upregulate ANXA2 and
accumulate S100A10. Increased AIIt promoted IRPG and invasiveness, both of which
were partly abolished by antibodies against ANXA2 and S100A10 or by ATRA.
PMID- 28687977
TI - Invasive mucinous adenocarcinoma with lepidic-predominant pattern coexisted with
tuberculosis: a case report.
AB - We observed a rare case of invasive mucinous adenocarcinoma (IMA) with a lepidic
predominant pattern accompanied by pulmonary tuberculosis. An 85-year-old man
with repeated cough and sputum was admitted to Xinhua Hospital. T-SPOT test
result was 212 pg/ml (reference value of negative is < 14 pg/ml), Mycobacterium
tuberculosis culture was positive, and tuberculin skin test (PPD) was negative
(skin induration < 5 mm). The patient was treated with several courses of
antibiotics and anti-tuberculosis treatments. Repeated chest CT scans showed
disease progression. Bronchoscopy yielded negative results. PET-CT scans showed
negative results. A percutaneous lung biopsy revealed mucin-secreting cells
lining the alveolar walls. IMA with a lepidic-predominant pattern was diagnosed
after invasiveness was found after experimental treatments. Simultaneous
occurrence of pulmonary tuberculosis and lung cancer are common; however, the
present case of IMA having a lepidic-predominant pattern and coexisting with
active tuberculosis has not been reported yet.
PMID- 28687978
TI - Two new Leptographium spp. reveal an emerging complex of hardwood-infecting
species in the Ophiostomatales.
AB - Species of Leptographium are generally characterized by mononematous
conidiophores and are commonly associated with bark beetles and weevils. These
species are responsible for sapstain and in some cases serious diseases on a
range of primarily coniferous trees. In comparison with coniferous trees, the
occurrence of Leptographium species on hardwood trees has been poorly studied in
Europe. During a survey of ophiostomatoid fungi on various tree species in Norway
and Poland, three unusual species, which fit the broader morphological
description of Leptographium spp., were found in association with Scolytus
ratzeburgi, Dryocoetes alni and Trypodendron domesticum on a variety of
hardwoods, and from wounds on Tilia cordata. Phylogenetic analyses of sequence
data for three gene regions (ITS2-LSU, beta-tubulin, and TEF1-alpha) showed that
these Leptographium species are phylogenetically closely related to each other
and form a well-supported lineage that included Grosmannia grandifoliae and
Leptographium pruni. The first species could be distinguished from the other
Leptographium species based on conidiophores arising from spiral hyphae,
chlamydospore-like structures and a hyalorhinocladiella-like synanamorph in
culture. The second species differs from the previous one by having distinctly
shorter conidiophores and smaller conidia. This species also produces a well
developed sporothrix-like synanamorph with denticulate conidiogenous cells. Based
on these unusual morphological characteristics and distinct DNA sequences, these
fungi were recognised as new taxa for which the names Leptographium trypodendri
sp. nov. and L. betulae sp. nov. are provided. The third group of isolates
belonged to Grosmannia grandifoliae, representing the first report of this
species outside of the USA. The newly defined G. grandifoliae complex is the
first species complex in Leptographium s.l. consisting of only hardwood-infecting
species.
PMID- 28687979
TI - "Radio-oncomics" : The potential of radiomics in radiation oncology.
AB - INTRODUCTION: Radiomics, a recently introduced concept, describes quantitative
computerized algorithm-based feature extraction from imaging data including
computer tomography (CT), magnetic resonance imaging (MRT), or positron-emission
tomography (PET) images. For radiation oncology it offers the potential to
significantly influence clinical decision-making and thus therapy planning and
follow-up workflow. METHODS: After image acquisition, image preprocessing, and
defining regions of interest by structure segmentation, algorithms are applied to
calculate shape, intensity, texture, and multiscale filter features. By combining
multiple features and correlating them with clinical outcome, prognostic models
can be created. RESULTS: Retrospective studies have proposed radiomics
classifiers predicting, e. g., overall survival, radiation treatment response,
distant metastases, or radiation-related toxicity. Besides, radiomics features
can be correlated with genomic information ("radiogenomics") and could be used
for tumor characterization. DISCUSSION: Distinct patterns based on data-based as
well as genomics-based features will influence radiation oncology in the future.
Individualized treatments in terms of dose level adaption and target volume
definition, as well as other outcome-related parameters will depend on radiomics
and radiogenomics. By integration of various datasets, the prognostic power can
be increased making radiomics a valuable part of future precision medicine
approaches. CONCLUSION: This perspective demonstrates the evidence for the
radiomics concept in radiation oncology. The necessity of further studies to
integrate radiomics classifiers into clinical decision-making and the radiation
therapy workflow is emphasized.
PMID- 28687980
TI - Exposure of vital cells to necrotic cell lysates induce the IRE1alpha branch of
the unfolded protein response and cell proliferation.
AB - Necrosis is a form of cell death that is detrimental to the affected tissue
because the cell ruptures and releases its content (reactive oxygen species among
others) into the extracellular space. Clusterin (CLU), a cytoprotective
extracellular chaperone has been shown to be upregulated in the face of necrosis.
We here show that in addition to CLU upregulation, necrotic cell lysates induce
JNK/SAPK signaling, the IRE1alpha branch of the unfolded protein response (UPR),
the MAPK/ERK1/2, and the mTOR signaling pathways and results in an enhanced
proliferation of the vital surrounding cells. We name this novel response
mechanism: Necrosis-induced Proliferation (NiP).
PMID- 28687981
TI - Characteristics and expression of genes encoding two small heat shock protein
genes lacking introns from Chilo suppressalis.
AB - Small heat shock proteins (sHSPs) constitute a large, diverse, and functionally
uncharacterized family of heat shock proteins. To gain insight regarding the
function of sHSPs in insects, we identified genes encoding two sHSPs, Cshsp22.9b
and Cshsp24.3, from the rice pest Chilo suppressalis. The cDNAs of Cshsp22.9b and
Cshsp24.3 encoded proteins of 206 and 216 amino acids with isoelectric points of
5.79 and 9.28, respectively. Further characterization indicated that both
Cshsp22.9b and Cshsp24.3 lacked introns. Real-time quantitative PCR indicated
that Cshsp22.9b and Cshsp24.3 were expressed at higher levels within the fat body
as compared to other tissues (head, epidermis, foregut, midgut, hindgut,
Malpighian tubules, and hemocytes). Expression of Cshsp22.9b and Cshsp24.3 was
lowest in the hindgut and Malpighian tubules, respectively. Cshsp22.9b and
Cshsp24.3 showed identical patterns in response to thermal stress from -11 to 43
degrees C, and both genes were up-regulated by hot and cold temperatures. The
mRNA (messenger ribonucleic acid) expression levels of Cshsp22.9b (KY701308) and
Cshsp24.3 (KY701309) were highest after a 2-h exposure at 39 degrees C and
started to decline at 42 degrees C. In response to cold temperatures, both
Cshsp22.9b and Cshsp24.3 showed maximal expression after a 2-h exposure to -3
degrees C. The two Cshsps were more responsive to hot than cold temperature
stress and were not induced by mildly cold or warm temperatures. In conclusion,
Cshsp22.9b and Cshsp24.3 could play a very important role in the regulation of
physiological activities in C. suppressalis that are impacted by environmental
stimuli.
PMID- 28687982
TI - Adductor canal block in combination with posterior capsular infiltration on the
pain control after TKA.
AB - BACKGROUND: Adductor canal block (ACB) and local infiltration anesthesia (LIA)
are both widely accepted techniques for postoperative pain control without
quadriceps weakness after total knee arthroplasty (TKA). However, the above
techniques are insufficient in efficacy or duration. AIMS: The aim of our study
was to address whether ACB plus posterior capsular infiltration (PCI) result in
improved analgesia compared with ACB or LIA in patients underwent TKA during 48 h
after operation. METHODS: Sixty patients were included: ACB group (group A, ACB
with 0.375% ropivacaine 30 ml, n = 20), ACB + PCI group (group B, ACB same as
group A, PCI with 0.2% ropivacaine 50 ml, n = 20), LIA group (group C, local
infiltration with 0.2% ropivacaine 100 ml, n = 20). VAS pain scores, rescue
analgesic tramadol consumption, nausea and vomiting occurrence, and patient
satisfaction were recorded at 4, 8, 24, and 48 h post-operation. RESULTS: Group
B, versus group A, had lower pain scores (at rest and during mobilization) at 4
to 8 h post-operation (P < 0.017). As compared with group C, only at 24 h post
operation, group B had statistically decreased rest and active pain scores (p =
0.016 and 0.014, respectively). There were no statistical differences in total
tramadol consumption and nausea and vomiting occurrence among the three groups.
However, there was improved patient satisfaction in group B. CONCLUSIONS:
Overall, as compared with ACB or LIA, ACB plus PCI appeared to provide more ideal
analgesia and patient satisfaction in the first 24 h after operation.
PMID- 28687983
TI - Sensing Tryptophan Microenvironment of Amyloid Protein Utilizing Wavelength
Selective Fluorescence Approach.
AB - Structural transition among various forms of proteins involves subtle interplay
between structure and dynamics and is crucial in human diseases. Red edge
excitation shift (REES) represents a suitable approach to explore the
environmental organization and dynamics surrounding tryptophan residues in
proteins. Although REES from tryptophan residues has been reported for native,
molten globule and denatured states of proteins, such data on the amyloid form of
proteins is lacking. kappa-casein is one of the most important constituents of
casein micelles in milk and has a tendency to form amyloid fibril. We report here
REES of the sole tryptophan residue for native, acid-denatured and urea-denatured
forms of kappa-casein. More importantly, we show that the amyloid form of kappa
casein displays REES of 4 nm. We analyze these results in terms of tryptophan
microenvironment in various forms of kappa-casein, particularly the amyloid form.
We conclude that REES is a sensitive tool to monitor structural plasticity in
proteins.
PMID- 28687984
TI - Comparison of the Optoelectronic Performance of Neutral and Cationic Forms of
Riboflavin.
AB - The riboflavin dye 2,3,4,5-tetra-O-acetyl-1-[3-(6-bromohexyl)-7,8-dimethyl-2,4
dioxo-3,4-dihydrobenzo[g]pteridin-10(2H)-yl]-1-deoxypentitol and its pyridinium
salt were synthesized, and studied by absorption and fluorescence spectroscopy in
solutions and on thin film states. The first absorption band of riboflavin
pyridinium salt derivative is red-shifted by 10 nm compared to neutral one on
film. Cationic riboflavin derivative shows significant wavelength changes on its
fluorescence emission spectrum in the excited state depending on the solvent
polarity and the electronic environment. The fluorescence quantum yields of
cationic riboflavin gave much higher values as compared to that of its neutral
form. The fluorescence lifetimes were found to be in the range of 5.5-6.6 ns with
mono - exponential behavior. These dyes possess low-lying HOMO energy levels
which are suitable to be able to inject holes to donor polymers so that they can
be used as acceptor component in the active layer of bulk heterojunction solar
cells (BHJ-SCs). Photovoltaic responses are reported for P3HT:riboflavin active
layer wherein the synthesized dyes are used as acceptor component. Also, neutral
riboflavin shows greater electron mobility value of 1.3 * 10-3 cm2/V?s compared
to its cationic derivative.
PMID- 28687985
TI - A Method for In Vitro Measurement of Oxidized Low-Density Lipoprotein in Blood,
Using Its Antibody, Fluorescence-Labeled Heptapeptide and Polyethylene Glycol.
AB - Two oxidized forms of low-density lipoprotein (LDL), oxidized (Ox-LDL) and
minimally modified (MM-LDL), and the immune complexes (LDL-ICs) that they form
with their corresponding antibodies, play a major role in the pathogenesis of
atherosclerosis. Recently, we reported that the heptapeptide KP6 (Lys-Trp-Tyr-Lys
Asp-Gly-Asp) coupled through its epsilon-amino group present on the N-terminal
Lys to fluorescein isothiocyanate (FITC)- (FITC)KP6- binds specifically to Ox-LDL
and MM-LDL, but not to native LDL. Here, to develop a novel method for measuring
the levels of oxidatively modified LDL in blood, using (FITC)KP6, we analyzed the
latter's binding with MM-LDL-IC and Ox-LDL-IC. Polyacrylamide gel electrophoresis
analysis revealed that (FITC)KP6 could efficiently and specifically bind to
polyethylene glycol (PEG)-precipitated MM-LDL-IC and Ox-LDL-IC in a dose
dependent manner with high sensitivity in plasma and serum. Our results indicate
that the above method for measuring the levels of PEG-precipitated, oxidatively
modified LDL-ICs, formed by the addition of anti-Ox-LDL antibody to blood, using
(FITC)KP6, can aid the diagnosis of atherosclerosis.
PMID- 28687987
TI - Evaluation of the Crystallization Tendency of Commercially Available Amorphous
Tacrolimus Formulations Exposed to Different Stress Conditions.
AB - PURPOSE: Tacrolimus, an immunosuppressant, is a poorly water soluble compound
whereby the commercially available capsule formulations contain the drug in
amorphous form. The goal of this study was to evaluate the robustness of the
innovator product and five generic formulations to crystallization following
storage at stress conditions. METHODS: Products were purchased from a pharmacy
and stored at 40 degrees C/75% relative humidity (RH), open dish conditions.
Crystallinity was determined using X-ray diffraction. The quantity of the
ingredients in the formulations were determined using different approaches and
the various factors that might cause instability in the formulations were
studied. RESULTS: After 4 weeks of open dish storage at 40 degrees C/75% RH, one
of the generic formulations showed evidence of tacrolimus crystallization.
Further investigations revealed batch-to-batch variations in crystallization
tendency with the extent of crystallinity varying between 50 and 100% for
different batches. Crystallization was also observed at lower storage
temperatures (30 degrees C) when the RH was maintained at 75%. It was found that
crystallization could be induced in a model formulation by wet granulating an
ethanolic solution of the drug with lactose and drying at 60-70 degrees C
followed by exposure to stress conditions. CONCLUSIONS: It seems probable that
the generic that was susceptible to crystallization contains amorphous drug
physically mixed with polymeric excipients, rather than as an amorphous solid
dispersion. This study highlights the importance of considering the manufacturing
process on the stability of the resultant amorphous product.
PMID- 28687988
TI - Initial and late efficacy of everolimus-eluting stents for small and non-small
coronary lesions from evaluating delayed late loss study.
AB - The aim of the present study was to evaluate the long-term outcomes at 2 years in
patients in whom everolimus-eluting stents (EESs) were implanted in small and non
small vessels. A small vessel is an important risk factor for restenosis with
BMSs, even in the first generation DESs. The 690 patients with 690 lesions
implanted with an EES were enrolled and divided into two groups by vessel
reference diameter (RD): >2.5 mm for non-small vessels (Non-S-group) and <=2.5 mm
for small vessels (S-group). Two years later, the 365 patients with no restenosis
at 8 months who underwent angiography were enrolled into the late catch-up study.
At the initial 8-month follow-up, the rates of restenosis and target lesion
revascularization (TLR) of both groups were not significantly different
(restenosis 3.9 vs 6.5%, p = 0.17; TLR 3.9 vs 6.5%, p = 0.17). At the late 2-year
follow-up, there were no significant differences in the late loss (0.36 +/- 0.66
vs 0.34 +/- 0.50 mm, p = 0.14), net gain (1.50 +/- 0.75 vs 1.26 +/- 0.60 mm, p =
0.39), late catch-up restenosis rate (5.1 vs 3.4%, p = 0.38), TLR (4.9 vs 2.7%, p
= 0.40), and delayed late loss (0.14 +/- 0.58 vs 0.15 +/- 0.49 mm, p = 0.10)
between both groups. There is no correlation between delayed late loss and RD in
all patients(r = -0.009) and in AMI patients (r = -0.004). These results
demonstrate that the initial and late catch-up restenosis rates of small coronary
vessels with EES placement were excellent, the same as for non-small coronary
vessels. We suggest that involvement of small coronary arteries may not be a risk
factor for restenosis and results of stenting for small coronary arteries with
EES placement were excellent.
PMID- 28687986
TI - Insights from a Systematic Search for Information on Designs, Costs, and
Effectiveness of Poliovirus Environmental Surveillance Systems.
AB - Poliovirus surveillance plays a critical role in achieving and certifying
eradication and will play a key role in the polio endgame. Environmental
surveillance can provide an opportunity to detect circulating polioviruses prior
to the observation of any acute flaccid paralysis cases. We completed a
systematic review of peer-reviewed publications on environmental surveillance for
polio including the search terms "environmental surveillance" or "sewage," and
"polio," "poliovirus," or "poliomyelitis," and compared characteristics of the
resulting studies. The review included 146 studies representing 101 environmental
surveillance activities from 48 countries published between 1975 and 2016.
Studies reported taking samples from sewage treatment facilities, surface waters,
and various other environmental sources, although they generally did not present
sufficient details to thoroughly evaluate the sewage systems and catchment areas.
When reported, catchment areas varied from 50 to over 7.3 million people (median
of 500,000 for the 25% of activities that reported catchment areas, notably with
60% of the studies not reporting this information and 16% reporting insufficient
information to estimate the catchment area population size). While numerous
studies reported the ability of environmental surveillance to detect polioviruses
in the absence of clinical cases, the review revealed very limited information
about the costs and limited information to support quantitative population
effectiveness of conducting environmental surveillance. This review motivates
future studies to better characterize poliovirus environmental surveillance
systems and the potential value of information that they may provide in the polio
endgame.
PMID- 28687989
TI - Screening novel autoantigens targeted by serum IgG autoantibodies in
immunorelated pancytopenia by SEREX.
AB - Immunorelated pancytopenia (IRP) is characterized by pancytopenia caused by
autoantibody-mediated destruction or suppression of bone marrow. However, the
autoantigens targeted by autoantibodies in IRP remain unclear. In the present
study, we screened novel autoantigens in IRP by serological analysis of
recombinant cDNA expression libraries and compared anti-UQCR10 antibody levels
between IRP and normal controls detected by immunoblotting. Our results indicate
that we successfully constructed the K562 cDNA library, which we used to screen
seven candidate autoantigens expressed in haematopoietic cells of IRP: ferritin,
light polypeptide, ubiquinol-cytochrome c reductase, complex III subunit X
(UQCR10), multifunctional methyl-transferase subunit TRM112-like protein isoform
1 (TRMT112), hemoglobin gamma-G, stathmin 1 (STMN1), transcript variant 3,
phosphoglycerate kinase 1 (PGK1), and trafficking protein particle complex
subunit 4 (TRAPPC4). Six of 17 (35.29%) IRP patients exhibited positive
reactivity to UQCR10 antigen, while only one of 10 (10%) of normal controls
reacted to UQCR10 antigen. The IRP patients with positive reactivity to UQCR10
antigen exhibited significantly improved total efficiency (6/6) compared with
those with negative reactivity (5/11). Thus, UQCR10 may be implicated as one of
the autoantigens involved in development of IRP.
PMID- 28687990
TI - CD34-negative hematopoietic stem cells show distinct expression profiles of
homing molecules that limit engraftment in mice and sheep.
AB - We and others have reported that human hematopoietic stem cells (HSCs) are also
present in the CD34-negative (CD34-) fraction of human cord blood (CB). Here, we
examined the hematopoietic engraftment potential of 13 or 18 lineage-negative
(13Lin- or 18Lin-) CD34+/- cells from human CB in mice and sheep. Both 13Lin- and
18Lin- CD34+ cells efficiently engrafted in mice irrespective of transplantation
route, be it by tail-vein injection (TVI) or by intra-bone marrow injection
(IBMI). These cells also engrafted in sheep after in utero fetal intra-hepatic
injection (IHI). In contrast, neither 13Lin- nor 18Lin- CD34- cells engrafted in
either mice or sheep when transplanted by regular routes (i.e., TVI and fetal
IHI, respectively), although both 13Lin- and 18Lin- CD34- cells engrafted in mice
when transplanted by IBMI and exhibited multilineage reconstitution ability.
Thus, the homing ability of CD34- HSCs is significantly more limited than that of
CD34+ HSCs. As for 18Lin-, CD34- HSCs are characterized by low expression of the
tetraspanin CD9, which promotes homing, and high expression of the peptidase
CD26, which inhibits homing. This unique expression pattern homing-related
molecules on CD34- HSCs could thus explain in part their reduced ability to home
to the BM niche.
PMID- 28687992
TI - The SIPIBEL project: treatment of hospital and urban wastewater in a conventional
urban wastewater treatment plant.
AB - Hospital wastewater (HWW) receives increasing attention because of its specific
composition and higher concentrations of some micropollutants. Better knowledge
of HWW is needed in order to improve management strategies and to ensure the
preservation of wastewater treatment efficiency and freshwater ecosystems. This
context pushed forward the development of a pilot study site named Site Pilote de
Bellecombe (SIPIBEL), which collects and treats HWW separately from urban
wastewater, applying the same conventional treatment process. This particular
configuration offers the opportunity for various scientific investigations. It
enables to compare hospital and urban wastewater, the efficiency of the two
parallel treatment lines, and the composition of the resulting hospital and urban
treated effluents, as well as the evaluation of their effects on the environment.
The study site takes into account environmental, economic, and social issues and
promotes scientific and technical multidisciplinary actions. ?.
PMID- 28687991
TI - Retrospective analysis of prognostic factors for Waldenstrom macroglobulinemia: a
multicenter cooperative study in Japan.
AB - Although population-based cancer registries have reported lower incidence of
Waldenstrom macroglobulinemia (WM) in East Asia than in Western countries,
previous retrospective analyses have found the clinical features of WM to be
similar in these two populations. To clarify the characteristics of Japanese WM
patients, we retrospectively analyzed clinical and laboratory characteristics,
treatments, outcomes, and prognostic factors in 93 patients with WM. Based on the
Second International Workshop on WM (IWWM-2) criteria, symptomatic WM was found
in 73 (78.5%) and asymptomatic WM in 20 (21.5%) of cases examined. The median
overall survival (OS) was similar to that in reports from Western countries.
Patients receiving treatment regimens including rituximab exhibited significantly
better survival than those not given rituximab. Although prognostic factors for
WM in Western countries may not apply to Japanese patients, our finding that
newly diagnosed WM patients with pleural effusion have a poorer prognosis
suggests that this may be a novel predictor of adverse prognosis in symptomatic
WM.
PMID- 28687993
TI - Rapid total sulphur reduction in coal samples using various dilute alkaline
leaching reagents under microwave heating: preventing sulphur emissions during
coal processing.
AB - Currently in South Africa, online flue gas desulphurisation (FGD) is being
utilized as one of the most effective methods for total sulphur reduction in coal
samples during the combustion process. However, the main disadvantage associated
with FGD is the formation of its by-products (FGD gypsum). The latter is mostly
formed in low grade quality, thereby bringing secondary pollution problems and
extra disposal costs. Therefore, the current study describes the development of
total sulphur extraction in coal under microwave heating using different dilute
alkaline solutions such as NaOH, NaOH-H2O2, NH4OH, and NH4OH-H2O2. The
experimental conditions were as follows: 150 degrees C, 5 min and 10% (m/v or
v/v) for temperature, extraction time and reagent concentration, respectively.
The most effective alkaline reagent for coal desulphurisation was observed to be
NaOH-H2O2 with total sulphur reduction of 55% (from the inductively coupled
plasma-optical emission spectrometry (ICP-OES) results). The NaOH-H2O2 reagent
also showed significant morphological changes in coal as observed from the SEM
images and effective demineralisation as revealed by the powder X-ray
diffractometer (P-XRD) results. Additionally, desulphurisation results obtained
from the developed microwave-assisted dilute alkaline extraction (MW-ADAE) method
were quite comparable with the published work. The proposed total sulphur
reduction method is advantageous as compared to some of the literature reported
coal desulphurisation methods as it requires a short period (5 min) of time to
reach its completion. Additionally, the proposed method shows excellent
reproducibility (% RSD from 0.5 to 1); therefore, it can be utilized for routine
analysis. Graphical abstract ?.
PMID- 28687994
TI - Measurement and decomposition of energy efficiency of Northeast China-based on
super efficiency DEA model and Malmquist index.
AB - Nowadays, environment problem has become the international hot issue. Experts and
scholars pay more and more attention to the energy efficiency. Unlike most
studies, which analyze the changes of TFEE in inter-provincial or regional
cities, TFEE is calculated with the ratio of target energy value and actual
energy input based on data in cities of prefecture levels, which would be more
accurate. Many researches regard TFP as TFEE to do analysis from the provincial
perspective. This paper is intended to calculate more reliably by super
efficiency DEA, observe the changes of TFEE, and analyze its relation with TFP,
and it proves that TFP is not equal to TFEE. Additionally, the internal
influences of the TFEE are obtained via the Malmquist index decomposition. The
external influences of the TFFE are analyzed afterward based on the Tobit models.
Analysis results demonstrate that Heilongjiang has the highest TFEE followed by
Jilin, and Liaoning has the lowest TFEE. Eventually, some policy suggestions are
proposed for the influences of energy efficiency and study results.
PMID- 28687995
TI - Mass-loss rates from decomposition of plant residues in spruce forests near the
northern tree line subject to strong air pollution.
AB - Mass-loss rates during the early phase of decomposition of plant residues were
studied for a period of 3 years in Norway spruce forests subjected to air
pollution by Cu-Ni smelters on the Kola Peninsula, northwest Russia. Litterbags
were deployed in two main patches of forests at the northern tree line, between
and below the crowns of spruce trees older than 100 years. The study results
demonstrated the dependence of the decomposition rates on the initial
concentrations of nutrients and the C/N and lignin/N ratios in plant residues.
Lower rates of mass loss in forests subject to air pollution may be related to
low quality of plant residues, i.e. high concentrations of heavy metals, low
concentrations of nutrients, and high lignin/N and C/N ratios. The increased
losses of Ca, Mg, K, and Mn from plant residues in these forests compared to the
reference were, probably, related to leaching of their compounds from the
residues. The relatively high rates of heavy metal accumulation in the residues
were most likely related to uptake of pollutants from the atmosphere, as well as
to the lower mass-loss rates. The present study results demonstrate that the
forest patchiness should be taken into account in assessment and predictions of
decomposition rates in Norway spruce forests. Mass-loss rates of plant residues
below the crowns of old spruce trees were significantly lower than those in the
patches between the crowns. This was explained by the high C/N and lignin/N
ratios in the residues of evergreens which contribute significantly to litterfall
below the crowns and by lower soil temperature during winter and spring below the
crowns. In addition, a lower amount of precipitation reaching the forest floor
below the dense, long crowns of old Norway spruce trees may result in
considerably lower washing out of the organic compounds from the residues. Lower
mass-loss rates below the crowns of old spruce trees may be part of the evidence
that the old-growth spruce forests can continue to accumulate carbon in soil.
PMID- 28687996
TI - Distribution and evolution of sterols and aliphatic hydrocarbons in dated marine
sediment cores from the Cabo Frio upwelling region, SW Atlantic, Brazil.
AB - We report the distribution of selected lipid biomarkers specifically sterols and
aliphatic hydrocarbons in sediment cores from Cabo Frio, SW Atlantic continental
shelf, Brazil, corresponding approximately to the last 700 years. In the Cabo
Frio region, a costal upwelling occurs as a quasi-seasonal phenomenon
characterized by nutrient-rich bottom waters that intrude on the continental
shelf and promote relatively high biological productivity compared to other
Brazilian continental shelf areas. The results for sterols indicate the
predominance of organic matter (OM) inputs related to marine organisms, mainly
plankton, in all of the cores along the time scale studied. Principal component
analyses show three different groups of variables, which may be associated with
(i) the more effective intrusion of the nutrient-rich South Atlantic Central
Water, resulting in the increase of marine lipid biomarkers such as sterols and
short-chain n-alkanes; (ii) the influence of the Coastal Water with higher
surface water temperature and subsequently lower primary productivity; and (iii)
OM characterized by high total organic carbon and long-chain n-alkanes related to
an allochthonous source. Relatively high concentrations of sterols and n-alkanes
between 1450 and 1700 AD, chronologically associated with the Little Ice Age,
suggest a period associated with changes in the local input of specific sources
of these compounds. The concentrations of lipid biomarkers vary over core depth,
but this does not suggest a notably high or low intensity of upwelling processes.
It is possible that the climatic and sea surface temperature changes reported in
previous studies did not affect the input of the sedimentary lipid biomarkers
analyzed here.
PMID- 28687997
TI - Interpretation of single and competitive adsorption of cadmium and zinc on
activated carbon using monolayer and exclusive extended monolayer models.
AB - In this work, a modeling analysis based on experimental tests of cadmium/zinc
adsorption, in both single-compound and binary systems, was carried out. All the
experimental tests were conducted at constant pH (around neutrality) and
temperature (20 degrees C). The experimental results showed that the zinc
adsorption capacity was higher than that of cadmium and it does not depend on
cadmium presence in binary system. Conversely, cadmium adsorption is affected by
zinc presence. In order to provide good understanding of the adsorption process,
two statistical physics models were proposed. A monolayer and exclusive extended
monolayer models were applied to interpret the single-compound and binary
adsorption isotherms of zinc and cadmium on activated carbon. Based on these
models, the modeling analysis demonstrated that zinc is dominant in solution and
more favorably adsorbed on activated carbon surface. For instance, in single
compound systems, the number of ions bound per each receptor site was n (Zn2+) =
2.12 > n (Cd2+) = 0.98. Thus, the receptor sites of activated carbon are more
selective for Zn2+ than for Cd2+. Moreover, the determination of adsorption
energy through the adopted models confirmed that zinc is more favored for
adsorption in single-compound system (adsorption energies equal to 12.12 and 7.12
kJ/mol for Zn and Cd, respectively) and its adsorption energy does not depend on
the cadmium presence in binary system. Finally, the adsorption energy values
suggested that single-compound and binary adsorption of zinc and cadmium is a
physisorption.
PMID- 28687998
TI - Effects of low to moderate levels of deoxynivalenol on feed and water intake,
weight gain, and slaughtering traits of broiler chickens.
AB - The aim of the study was to evaluate the effects of low to moderate oral exposure
to the Fusarium toxin deoxynivalenol (DON; derived from culture material) on
performance, water intake, and carcass parameters of broilers during early and
late developmental phases. A total of 160 Ross 308 broilers were randomly
allocated to four different feeding groups (n = 40/group) including 0 (control),
2.5, 5, and 10 mg DON/kg wheat-soybean meal-based feed. Three consecutive
replicates of the experiment were performed. Half of the broilers were
slaughtered in week 3 of the trial whereas the other half were slaughtered in
week 5. Dry matter intake (DMI) and water intake (WI) were recorded on a daily
basis and the body weight (BW) and BW gain (BWG) were determined weekly. The
following carcass traits were recorded and calculated in absolute and relative
data: dressed carcass weight, breast muscle weight, leg weight, and liver weight.
Data showed that BW (P < 0.001), BWG (P = 0.005), and DMI (P < 0.001) were
reduced by DON-feeding during the entire feeding period. The ratio of DMI to body
weight gain (DMI/BWG) was not affected by the treatment. However, the ratio of
water to DMI (WI/DMI) increased in DON-treated birds (P = 0.021). Contrast
analysis showed that DON tendentially reduced slaughter weight (P = 0.082) and
decreased leg yield (P = 0.037) in DON-fed chickens in week 5 of the experiment.
Liver organ weight decreased in the 3-week-old DON-fed broilers compared to that
in the control-fed birds (P = 0.037). In conclusion, the study suggests that DMI
and BW were negatively affected under the experimental conditions at DON levels
lower than the current guidance value in the European Union of 5 mg/kg feed. The
study also indicates that broilers fed on low to moderate level DON-contaminated
diets showed increased WI/DMI ratio which might have negative influence on wet
litter syndrome.
PMID- 28687999
TI - Use of yeast (Pichia kudriavzevii) as a novel feed additive to ameliorate the
effects of aflatoxin B1 on broiler chicken performance.
AB - The aim of this study was to evaluate the efficacy of autochthonous Pichia
kudriavzevii as a novel bioadsorbent for aflatoxin B1 (AFB1). The selection of
this yeast was based on the AFB1 adsorption capacity previously demonstrated in
vitro (Magnoli et al. 2016). One-day-old Cobb broilers (n = 160) were randomly
assigned to four dietary treatments (T1: basal diet (B); T2: B + 0.1% yeast; T3:
B + AFB1, 100 MUg/kg; T4: B + 0.1% yeast + AFB1, 100 MUg/kg). Performance
parameters (average daily weight gain body, average daily consumption, feed
conversion ratio, carcass weight, and dead weight), biochemical parameters
(albumin, globulin, and albumin/globulin), liver pathological changes, and AFB1
residual levels in the liver and excreta were evaluated. Significant differences
(P < 0.05) in performance parameters were observed among treatments and controls:
T3 group showed the lowest average daily body weight gain value while in T4
group, the value of this parameter increased significantly (P < 0.05). T3 and T4
groups showed the lowest and highest values for average daily feed consumption,
respectively. The feed conversion ratio (FC) showed no significant differences
among treatments. T3 group showed the lowest dead weight and carcass weight
compared with T1 group. The biochemical parameters showed no significant
differences among treatments. T3 group showed macroscopic and microscopic liver
changes compared to the control. Aflatoxin B1 levels (MUg/g) were detected in
broiler livers and showed significant differences among treatments (P < 0.05). In
conclusion, native P. kudriavzevii incorporation (0.1%) in broiler diets
containing AFB1 was shown to be effective in ameliorating the adverse effects of
AFB1 on production.
PMID- 28688000
TI - Is RPMI 2650 a Suitable In Vitro Nasal Model for Drug Transport Studies?
AB - The evaluation of new intranasal medications requires the development of in vitro
cell model suitable for high-throughput screening studies. The aim of a
pharmacological model is to closely mimic the barrier properties of human nasal
mucosa that will influence drug pharmacokinetics. In this context, the human
nasal cell line RPMI 2650 has been investigated over these last years. Although
the initial studies tended to demonstrate strong physiological correlations
between RPMI 2650 cells and nasal mucosa, the variability of experimental designs
does not allow a clear comparison of actual data. Thereby, the standardization of
cell culture parameters is crucial to obtain a stronger reproducibility and
increase the relevance of data. Indeed, RPMI 2650 barrier properties are heavily
dependent of cell culture conditions, especially of the physiological air-liquid
interface that strengthen the expression of both tight junction proteins and drug
transporters. Conversely, cell culture medium and insert composition showed a
minor impact on the four key parameters of a nasal barrier. Despite the recent
advances in the physiological characterization of RPMI 2650 model, only limited
pharmacological data are available concerning the involvement of drug
transporters in drug bioavailability. The deployment of standardized bi
directional permeability studies using reference compounds is required to
determine the relevance of RPMI 2650 model in the field of drug transport
studies.
PMID- 28688002
TI - Erratum to: The Lesion Analysis of Cholinergic Neurons in 5XFAD Mouse Model in
the Three-Dimensional Level of Whole Brain.
PMID- 28688001
TI - Pharmacokinetic Interactions and Safety of Coadministration of Glecaprevir and
Pibrentasvir in Healthy Volunteers.
AB - BACKGROUND AND OBJECTIVE: Glecaprevir and pibrentasvir are pangenotypic direct
acting antiviral agents for the treatment of chronic hepatitis C virus infection.
The aim of the present study was to evaluate the drug-drug interaction and safety
of glecaprevir and pibrentasvir coadministration in healthy volunteers. METHODS:
In this open-label, randomized, multiple-dose, Phase 1 study in 72 subjects,
glecaprevir (100-1200 mg once daily) and pibrentasvir (40-200 mg once daily) were
administered alone for 7 days and then in combination for another 7 days.
Intensive blood sampling was performed on Days 1, 7, 8, and 14, and
pharmacokinetic interactions were assessed using a repeated measures analysis of
glecaprevir and pibrentasvir maximum plasma concentration (C max) and area under
the curve (AUC). RESULTS: Coadministration of glecaprevir 400 mg increased
pibrentasvir 120 and 40 mg steady-state C max and AUC values to 2.9-6.3-fold, and
coadministration of glecaprevir 700 mg increased pibrentasvir 160 mg steady-state
C max and AUC24 values to up to sevenfold of the values when pibrentasvir was
administered alone. Glecaprevir C max and AUC values during coadministration were
less than 1.5-fold of the values when glecaprevir was administered alone. The
combination of glecaprevir and pibrentasvir at doses up to 400 mg was well
tolerated by the healthy subjects in this study. High glecaprevir exposures at
700 and 1200 mg were associated with grade 2/3 elevations in alanine
aminotransferase, aspartate aminotransferase, and/or bilirubin. CONCLUSIONS:
Coadministration of pibrentasvir 120 mg with glecaprevir doses up to 400 mg
resulted in increases in pibrentasvir exposures without significant changes in
glecaprevir exposures in the absence of any clinically significant laboratory
abnormalities.
PMID- 28688003
TI - Increased Training Intensity Induces Proper Membrane Localization of Actin
Remodeling Proteins in the Hippocampus Preventing Cognitive Deficits:
Implications for Fragile X Syndrome.
AB - Behavioral intervention therapy has proven beneficial in the treatment of autism
and intellectual disabilities (ID), raising the possibility of certain changes in
molecular mechanisms activated by these interventions that may promote learning.
Fragile X syndrome (FXS) is a neurodevelopmental disorder characterized by
autistic features and intellectual disability and can serve as a model to examine
mechanisms that promote learning. FXS results from mutations in the fragile X
mental retardation 1 gene (Fmr1) that prevents expression of the Fmr1 protein
(FMRP), a messenger RNA (mRNA) translation regulator at synapses. Among many
other functions, FMRP organizes a complex with the actin cytoskeleton-regulating
small Rho GTPase Rac1. As in humans, Fmr1 KO mice lacking FMRP display autistic
like behaviors and deformities of actin-rich synaptic structures in addition to
impaired hippocampal learning and synaptic plasticity. These features have been
previously linked to proper function of actin remodeling proteins that includes
Rac1. An important step in Rac1 activation and function is its translocation to
the membrane, where it can influence synaptic actin cytoskeleton remodeling
during hippocampus-dependent learning. Herein, we report that Fmr1 KO mouse
hippocampus exhibits increased levels of membrane-bound Rac1, which may prevent
proper learning-induced synaptic changes. We also determine that increasing
training intensity during fear conditioning (FC) training restores contextual
memory in Fmr1 KO mice and reduces membrane-bound Rac1 in Fmr1 KO hippocampus.
Increased training intensity also results in normalized long-term potentiation in
hippocampal slices taken from Fmr1 KO mice. These results point to interventional
treatments providing new therapeutic options for FXS-related cognitive
dysfunction.
PMID- 28688005
TI - Ab initio study of hydrogen bonding in the H3PO2 dimer and H3PO2-DMF complex.
AB - The molecular structures and H-bonding interactions in the phosphinic acid dimer
and the complex of phosphinic acid with N,N-dimethylformamide (DMF) were
investigated by density functional theory calculations at the B3LYP level of
theory. In order to better understand these phenomena, the individual molecules
were also studied. The results were compared with previously obtained data for
similar H-bonded complexes of phosphoric and phosphorous acids with DMF. Various
correlations were found between geometric characteristics and parameters derived
from Bader's theory and natural bond orbital analysis. Graphical abstract Irina
V. Fedorova and Lyubov P. Safonova. Ab initio study of hydrogen bonding in the
H3PO2 dimer and H3PO2-DMF complex. The acids of phosphorus are considered
suitable candidates for ionomers due to their efficient proton transport
properties. In order to better understand their molecular structures and their H
bond characteristics in real liquids, the most stable configurations of the H3PO2
dimer and the H3PO2-DMF complex were examined using computational methods in
quantum chemistry. It was found that the strength of the H-bonding interactions
in these systems depends strongly on the environment.
PMID- 28688004
TI - Do terrestrial gastropods use olfactory cues to locate and select food actively?
AB - Having been investigated for over 40 years, some aspects of the biology of
terrestrial gastropod's olfactory system have been challenging and highly
contentious, while others still remain unresolved. For example, a number of
terrestrial gastropod species can track the odor of food, while others have no
strong preferences toward food odor; rather they find it by random encounter.
Here, while assessing the most recent findings and comparing them with earlier
studies, the aspects of the food selection based on olfactory cues are examined
critically to highlight the speculations and controversies that have arisen. We
analyzed and compared the potential role of airborne odors in the feeding
behavior of several terrestrial gastropod species. The available results indicate
that in the foraging of most of the terrestrial gastropod species odor cues
contribute substantially to food finding and selection. The results also suggest,
however, that what they will actually consume largely depends on where they live
and the species of gastropod that they are. Due to the voluminous literature
relevant to this object, this review is not intended to be exhaustive. Instead, I
selected what I consider to be the most important or critical in studies
regarding the role of the olfaction in feeding of terrestrial gastropods.
PMID- 28688006
TI - Erratum to: Objection to postoperative radiation therapy in breast cancer with
one to three lymph nodes involvements.
PMID- 28688007
TI - How is patella height modified after total knee arthroplasty?
AB - INTRODUCTION: Since the first measurement method of patella height in 1929
(Janssen), more than 16 methods have been described. Most of these measures are
not suitable to measure patella height after total knee arthroplasty (TKA). One
of us (JC) modified the original Caton Deschamps (oCD), index with a new relative
index called modified Caton Deschamps (mCD) index, by using new landmarks. The
purpose of this study was to determine how patella height is modified after TKA.
MATERIAL AND METHOD: Sixty primary TKAs were consecutively prospectively
enrolled. One type of implant was used (cementless postero-stabilized TKA,
rotating plateau, cemented patella resurfacing). Patient's characteristics,
functional and radiological outcomes were recorded pre-operatively and at one
year follow-up. Pre-operative and post-operative outcomes were compared by paired
t-test. Post-operative outcomes were compared between groups by one-way analysis
of variance. RESULTS: Average difference between pre and post-operative mCD was
0.19 in this series. In 81.7% of cases, patella was lowered. Patients were
classified in three groups according to patella height lowering. Between these
three groups, no significant statistical differences (IKS score knee and
function, range of motion) could be identified. DISCUSSION: In TKA, patella
assessment in sagittal plane is as important as frontal or horizontal planes.
True patella infera (TPI) is mostly due to patella tendon shortening measured by
oCD. Pseudo patella infera (PPI) measured by mCD is mostly due to joint line
elevation (over femoral cut with an over thickness of the tibial component). In
this study a moderate patella lowering (minor than 15%) does not have a
significant impact on the functional results (IKS, ROM) nevertheless in 80%
patella is lowered. The next step will be to analyze precisely what factors are
influencing this lowering and what prevention could be suggested in primary and
revision TKA.
PMID- 28688008
TI - Pneumocystis jirovecii and Cystic Fibrosis in Brittany, France.
AB - Pneumocystis jirovecii is a transmissible fungus with a high pulmonary tropism.
The prevalence of P. jirovecii in patients with cystic fibrosis (CF) has been
estimated in Germany at 7.4%, in Spain at 21.5% and in Brazil at 38.2%. Data on
the prevalence of P. jirovecii in CF patients in France remain scarce,
particularly in Brittany, where the prevalence of CF is high (from 1/1600 to
1/4500). Our objectives were to determine the prevalence of colonization of the
airways by P. jirovecii in Brittany in CF patients monitored at the "Centre de
Ressources et de Competences de la Mucoviscidose (CRCM)" of Rennes compared to
that previously observed at the CRCM of Roscoff-Brest. Sputa from 86 patients
(178 specimens) followed in Rennes were analyzed retrospectively. The detection
of P. jirovecii was performed using real-time PCR targeting the gene encoding the
mitochondrial large subunit of ribosomal RNA. Pneumocystis jirovecii DNA was
detected in 3/86 patients (3.5%) monitored at Rennes, whereas it had previously
been detected in 1/76 patients (1.3%) monitored at Roscoff-Brest, thus showing an
overall prevalence of 2.5% in Brittany. These results obtained from two Breton
centers taken together show that P. jirovecii prevalence in patients with CF in
Brittany is lower than those observed in Germany, Spain, Brazil or in other
regions of France. This study is a preliminary step in determining the risk
factors for P. jirovecii acquisition, its epidemiological and clinical
significance in CF patients through a prospective multicenter study.
PMID- 28688009
TI - Comparing volume-clamp method and intra-arterial blood pressure measurements in
patients with atrial fibrillation admitted to the intensive or medium care unit.
AB - International guidelines highlight the importance of blood pressure (BP) in
patients with atrial fibrillation (AF). However, BP measurement in AF is
complicated by beat-to-beat fluctuation. Automated BP measurement devices are not
validated for patients with AF and no consensus exists on how to measure BP in AF
manually. Beat-to-beat BP measurement using the volume-clamp method (VCM) could
represent a non-invasive method to accurately assess BP, but has not been
validated in AF. 31 admitted patients with sustained AF and 10 control patients
with sinus rhythm underwent simultaneous intra-arterial and non-invasive BP
measurement using a VCM monitor (Nexfin(r), BMEYE, Amsterdam, The Netherlands).
Patients with compromised peripheral perfusion, high doses of vasopressor drugs
or peripheral edema were excluded. Differences in systolic, diastolic and mean BP
of 5 (standard deviation; SD 8) mmHg (accuracy and precision) between both
methods were considered acceptable. Additionally, the magnitude of beat-to-beat
fluctuations in systolic BP of both methods was compared. In AF, the differences
between noninvasive and invasive BP were -4 (SD 12), +1 (SD 7) and 0 (SD 8) mmHg
for systolic, diastolic and mean BP respectively. Absolute differences in beat-to
beat BP fluctuations were 1.5 (IQR 0.8-3.8) mmHg. Accuracy of VCM in AF was
similar to sinus rhythm. In conclusion, in patients with AF, accurate and precise
measurement of non-invasive beat-to-beat BP measurement using the VCM is
possible, the one exception being the precision of systolic BP. Beat-to-beat
variability can be accurately reproduced.
PMID- 28688010
TI - Quorum sensing molecules production by nosocomial and soil isolates Acinetobacter
baumannii.
AB - Acinetobacter species remain alive in hospitals on various surfaces, both dry and
moist, forming an important source of hospital infections. These bacteria are
naturally resistant to many antibiotic classes. Although the role of the quorum
sensing system in regulating the virulence factors of Acinetobacter species has
not been fully elucidated, it has been reported that they play a role in
bacterial biofilm formation. The biofilm formation helps them to survive under
unfavorable growth conditions and antimicrobial treatments. It is based on the
accumulation of bacterial communication signal molecules in the area. In this
study, we compared the bacterial signal molecules of 50 nosocomial Acinetobacter
baumannii strain and 20 A. baumannii strain isolated from soil. The signal
molecules were detected by the biosensor bacteria (Chromobacterium violaceum 026,
Agrobacterium tumefaciens A136, and Agrobacterium tumefaciens NTL1) and their
separation was determined by thin-layer chromatography. As a result, it has been
found that soil-borne isolates can produce 3-oxo-C8-AHL and C8-AHL, whereas
nosocomial-derived isolates can produce long-chain signals such as C10-AHL, C12
AHL, C14-AHL and C16-AHL. According to these results, it is possible to
understand that these signal molecules are found in the infection caused by A.
baumannii. The inhibition of this signaling molecules in a communication could
use to prevent multiple antibiotic resistance of these bacteria.
PMID- 28688011
TI - Separation anxiety among birth-assigned male children in a specialty gender
identity service.
AB - Previous research suggested that separation anxiety disorder (SAD) is
overrepresented among birth-assigned male children clinic-referred for gender
dysphoria (GD). The present study examined maternally reported separation anxiety
of birth-assigned male children assessed in a specialty gender identity service
(N = 360). SAD was determined in relation to DSM-III and DSM-IV criteria,
respectively. A dimensional metric of separation anxiety was examined in relation
to several additional factors: age, ethnicity, parental marital status and social
class, IQ, gender nonconformity, behavioral and emotional problems, and poor peer
relations. When defined in a liberal fashion, 55.8% were classified as having
SAD. When using a more conservative criterion, 5.3% were classified as having
SAD, which was significantly greater than the estimated general population
prevalence for boys, but not for girls. Dimensionally, separation anxiety was
associated with having parents who were not married or cohabitating as well as
with elevations in gender nonconformity; however, the association with gender
nonconformity was no longer significant when statistically controlling for
internalizing problems. Thus, SAD appears to be common among birth-assigned males
clinic-referred for GD when defined in a liberal fashion, and more common than in
boys, but not girls, from the general population even when more stringent
criteria were applied. Also, the degree of separation anxiety appears to be
linked to generic risk factors (i.e., parental marital status, internalizing
problems). As such, although separation anxiety is common among birth-assigned
male children clinic-referred for GD, it seems unlikely to hold unique
significance for this population based on the current data.
PMID- 28688012
TI - Sex differences in risk-based decision making in adolescents with conduct
disorder.
AB - Altered decision making processes and excessive risk-seeking behaviours are key
features of conduct disorder (CD). Previous studies have provided compelling
evidence of abnormally increased preference for risky options, higher sensitivity
to rewards, as well as blunted responsiveness to aversive outcomes in adolescents
with CD. However, most studies published to date have focused on males only;
thus, it is not known whether females with CD show similar alterations in
decision making. The current study investigated potential sex differences in
decision making and risk-seeking behaviours in adolescents with CD. Forty-nine
adolescents with CD (23 females) and 51 control subjects (27 females), aged 11-18
years, performed a computerised task assessing decision making under risk-the
Risky Choice Task. Participants made a series of decisions between two gamble
options that varied in terms of their expected values and probability of gains
and losses. This enabled the participants' risk preferences to be determined.
Taking the sample as a whole, adolescents with CD exhibited increased risk
seeking behaviours compared to healthy controls. However, we found a trend
towards a sex-by-group interaction, suggesting that these effects may vary by
sex. Follow-up analyses showed that males with CD made significantly more risky
choices than their typically developing counterparts, while females with CD did
not differ from typically developing females in their risk-seeking behaviours.
Our results provide preliminary evidence that sex may moderate the relationship
between CD and alterations in risk attitudes and reward processing, indicating
that there may be sex differences in the developmental pathways and
neuropsychological deficits that lead to CD.
PMID- 28688015
TI - Erratum to: Health-Related Quality of Life in Patients with Multiple Sclerosis:
Impact of Disease-Modifying Drugs.
PMID- 28688016
TI - ArtiFacts: Richard Satterlee's Bone Saw.
PMID- 28688014
TI - Comparative proteomic analysis of Chlamydomonas reinhardtii control and a
salinity-tolerant strain revealed a differential protein expression pattern.
AB - MAIN CONCLUSION: Proteins involved in membrane transport and trafficking, stress
and defense, iron uptake and metabolism, as well as proteolytic enzymes, were
remarkably up-regulated in the salinity-tolerant strain of Chlamydomonas
reinhardtii. Excessive concentration of NaCl in the environment can cause adverse
effects on plants and microalgae. Successful adaptation of plants to long-term
salinity stress requires complex cellular adjustments at different levels from
molecular, biochemical and physiological processes. In this study, we developed a
salinity-tolerant strain (ST) of the model unicellular green alga, Chlamydomonas
reinhardtii, capable of growing in medium containing 300 mM NaCl. Comparative
proteomic analyses were performed to assess differential protein expression
pattern between the ST and the control progenitor cells. Proteins involved in
membrane transport and trafficking, stress and defense, iron uptake and
metabolism, as well as protein degradation, were remarkably up-regulated in the
ST cells, suggesting the importance of these processes in acclimation mechanisms
to salinity stress. Moreover, 2-DE-based proteomic also revealed putative
salinity-specific post-translational modifications (PTMs) on several important
housekeeping proteins. Discussions were made regarding the roles of these
differentially expressed proteins and the putative PTMs in cellular adaptation to
long-term salinity stress.
PMID- 28688013
TI - A Comprehensive Review of Neutrophilic Diseases.
AB - Neutrophilic dermatoses are a group of conditions characterized by the
accumulation of neutrophils in the skin and clinically presenting with
polymorphic cutaneous lesions, including pustules, bullae, abscesses, papules,
nodules, plaques and ulcers. In these disorders, the possible involvement of
almost any organ system has lead to coin the term 'neutrophilic diseases'.
Neutrophilic diseases have close clinicopathological similarities with the
autoinflammatory diseases, which present with recurrent episodes of inflammation
in the affected organs in the absence of infection, allergy and frank
autoimmunity. Neutrophilic diseases may be subdivided into three main groups: (1)
deep or hypodermal forms whose paradigm is pyoderma gangrenosum, (2) plaque-type
or dermal forms whose prototype is Sweet's syndrome and (3) superficial or
epidermal forms among which amicrobial pustulosis of the folds may be considered
the model. A forth subset of epidermal/dermal/hypodermal forms has been recently
added to the classification of neutrophilic diseases due to the emerging role of
the syndromic pyoderma gangrenosum variants, whose pathogenesis has shown a
relevant autoinflammatory component. An increasing body of evidence supports the
role of pro-inflammatory cytokines like interleukin (IL)-1-beta, IL-17 and tumour
necrosis factor (TNF)-alpha in the pathophysiology of neutrophilic diseases
similarly to classic monogenic autoinflammatory diseases, suggesting common
physiopathological mechanisms. Moreover, mutations of several genes involved in
autoinflammatory diseases are likely to play a role in the pathogenesis of
neutrophilic diseases, giving rise to regarding them as a spectrum of polygenic
autoinflammatory conditions. In this review, we focus on clinical aspects,
histopathological features and pathophysiological mechanisms of the paradigmatic
forms of neutrophilic diseases, including pyoderma gangrenosum, Sweet's syndrome,
amicrobial pustulosis of the folds and the main syndromic presentations of
pyoderma gangrenosum. A simple approach for diagnosis and management of these
disorders has also been provided.
PMID- 28688017
TI - What Factors Predict Conversion to THA After Arthroscopy?
AB - BACKGROUND: Failure of hip preservation to alleviate symptoms potentially
subjects the patient to reoperation or conversion surgery to THA, adding recovery
time, risk, and cost. A risk calculator using an algorithm that can predict the
likelihood that a patient who undergoes arthroscopic hip surgery will undergo THA
within 2 years would be helpful, but to our knowledge, no such tool exists.
QUESTIONS: (1) Are there preoperative and intraoperative variables at the time of
hip arthroscopy associated with subsequent conversion to THA? (2) Can these
variables be used to develop a predictive tool for conversion to THA? MATERIALS
AND METHODS: All patients undergoing arthroscopy from January 2009 through
December 2011 were registered in our longitudinal database. Inclusion criteria
for the study group were patients undergoing hip arthroscopy for a labral tear,
who eventually had conversion surgery to THA. Patients were compared with a
control group of patients who underwent hip arthroscopy for a labral tear but who
did not undergo conversion surgery to THA during the same study period. Of the
893 who underwent surgery during that time, 792 (88.7%) were available for
followup at a minimum of 2 years (mean, 31.1 +/- 8.1 years) and so were
considered in this analysis. Multivariate regression analyses of 41 preoperative
and intraoperative variables were performed. Using the results of the
multivariate regression, we developed a simplified calculator that may be helpful
in counseling a patient regarding the risk of conversion to THA after hip
arthroscopy. RESULTS: Variables simultaneously associated with conversion to THA
in this model were older age (rate ratio, 1.06; 95% CI, 1.03-1.08; p < 0.0001),
lower preoperative modified Harris hip score (rate ratio [RR], 0.98; 95% CI, 0.96
0.99; p = 0.0003), decreased femoral anteversion (RR, 0.97; 95% CI, 0.94-0.99; p
= 0.0111), revision surgery (RR, 2.4; 95% CI, 1.15-5.01; p = 0.0193), femoral
Outerbridge Grades II to IV (Grade II: RR, 2.23 [95% CI, 1.11-4.46], p = 0.023;
Grade III: RR, 2.17, [95% CI, 1.11-4.23], p = 0.024; Grade IV: RR, 2.96 [95% CI,
1.34-6.52], p = 0.007), performance of acetabuloplasty (RR, 1.83; 95% CI, 1.03
3.24; p = 0.038), and lack of performance of femoral osteoplasty (RR, 0.62; 95%
CI, 0.36-1.06; p = 0.081). Using the results of the multivariate regression, we
developed a simplified calculator that may be helpful in counseling a patient
regarding the risk of conversion surgery to THA after hip arthroscopy.
CONCLUSION: Multiple risk factors have been identified as possible risk factors
for conversion to THA after hip arthroscopy. A weighted calculator based on our
data is presented here and may be useful for predicting failure after hip
arthroscopy for labral treatment. Determining the best candidates for hip
preservation remains challenging; careful attention to long-term followup and
identifying characteristics associated with successful outcomes should be the
focus of further study. LEVEL OF EVIDENCE: Level III, therapeutic study.
PMID- 28688018
TI - Current Pathologic Scoring Systems for Metal-on-metal THA Revisions are not
Reproducible.
AB - BACKGROUND: The aseptic lymphocyte vasculitis-associated lesion (ALVAL) score and
the modified Oxford ALVAL score are frequently used scoring methods to evaluate
the morphologic features of periprosthetic tissues around metal-on-metal (MoM)
hip implants. Except for the initial studies of these two morphology scoring
methods, to our knowledge, no other studies have reported on intraclass
correlation coefficient (ICC) values for interobserver reliability of these
scoring methods. QUESTIONS/PURPOSES: Are the ALVAL and Oxford ALVAL scores
reproducible? METHODS: The periprosthetic tissue of 37 revisions of 36 patients
with failed MoM THAs were independently scored by three experienced pathologists
using ALVAL and Oxford ALVAL scoring methods. All patients were included who
underwent revision surgery in our hospital until January 2013, with a large-head
MoM prosthesis and also met the criteria: blood serum cobalt levels, available
MRI scan, and intraarticular cobalt levels. The population included 26 patients
with pseudotumors diagnosed by two radiologists using the method described by
Matthies et al. The ALVAL describes morphologic features of the synovial lining,
tissue organization, and inflammatory cell infiltrate in periprosthetic tissues.
The Oxford-ALVAL score uses a semiquantitative measure of the immune response
which should be easier to score. RESULTS: The ALVAL score showed an ICC of 0.38
(95% CI, 0.18-0.58) (fair) for the sum score and this improved up to 0.50 (95%
CI, 0.31-0.68) (moderate) using the modified Oxford ALVAL score. The individual
parameters of the ALVAL score showed an ICC for the scoring of inflammatory
infiltrate of 0.37 (95% CI, 0.17-0.57), an ICC of 0.32 (95% CI, 0.12-0.53) for
the scoring of tissue organization, and an ICC of 0.14 (95% CI, -0.04 to 0.34)
for synovial lining. CONCLUSIONS: Scoring morphologic features of MoM tissue is
not reproducible using the ALVAL score or the Oxford ALVAL score. This may
reflect heterogeneous morphologic features in tumor tissue and between different
tumor tissue samples that cannot be reliably quantified by pathologists using the
parameters of these two scoring methods. An alternative, simplified scoring
system should be developed to improve the interrater agreement. LEVEL OF
EVIDENCE: Level III, diagnostic study.
PMID- 28688019
TI - What Are the Risk Factors and Complications Associated With Intraoperative and
Postoperative Fractures in Total Wrist Arthroplasty?
AB - BACKGROUND: Total wrist arthroplasty (TWA) can relieve pain and preserve some
wrist motion in patients with advanced wrist arthritis. However, few studies have
evaluated the risks and outcomes associated with periprosthetic fractures around
TWAs. QUESTIONS/PURPOSES: (1) What is the risk of intraoperative and
postoperative fractures after TWAs? (2) What factors are associated with
increased risk of intraoperative and postoperative fracture after TWAs? (3) What
is the fracture-free and revision-free survivorship of TWAs among patients who
sustained an intraoperative fracture during the index TWA? METHODS: At one
institution during a 40-year period, 445 patients underwent primary TWAs. Of
those, 15 patients died before 2 years and 5 were lost to followup, leaving 425
patients who underwent primary TWAs with a minimum of 2-year followup. The
primary diagnosis for the TWA included osteoarthritis ([OA] 5%), inflammatory
arthritis (90%), and posttraumatic arthritis (5%). Indications for TWA included
pancarpal arthritis combined with marked pain and loss of wrist function. The
mean age of the patients was 57 years, BMI was 26 kg/m2, and 73% were females.
Six different implants were used during the 40-year period. Mean followup was 10
years (range, 2-18 years). RESULTS: Intraoperative fractures occurred in nine
(2%) primary TWAs, while postoperative fractures occurred after eight (2%) TWAs.
After analyzing demographics, comorbidities, and surgical factors, intraoperative
fractures were found to be associated with only age at surgery (hazard ratio
[HR], 1.10; 95% CI, 1.03-1.20; p = 0.006) and use of a bone graft (HR, 5.80; 95%
CI, 1.18-23.08; p = 0.03). No factors were found to be associated with increased
risk of postoperative fractures; specifically, intraoperative fracture was not
associated with subsequent fracture development. The 5-, 10-, and 15-year Kaplan
Meier survival rates free of postoperative fracture were 99%, 98%, and 95%,
respectively. The 5- and 10-year revision-free survival rates after
intraoperative fracture were 88% and 88%, respectively, compared with 84% and 74%
without an intraoperative fracture (p = 0.36). Furthermore, the survival-free of
revision surgery rates for aseptic distal loosening at 5 and 10 years were 88%
and 88%, respectively, compared with 93% and 87% without a fracture (p = 0.85).
CONCLUSIONS: Intraoperative fractures occur in approximately 2% of TWAs. These
fractures do not appear to affect long-term implant survival or risk of fracture.
Patient age and the need for bone graft were the only factors in the risk of
intraoperative fractures. Postoperative fractures also occur in 2% of TWAs, but
often result in revision surgery. LEVEL OF EVIDENCE: Level III, therapeutic
study.
PMID- 28688021
TI - Inaugural Conference on Incorporating Patient-Reported Outcomes and Patient
Preference Information into Clinical Research, Clinical Care, and Risk-Benefit
Assessments for Neurodegenerative Diseases.
PMID- 28688020
TI - Salvage Therapy Options for Local Prostate Cancer Recurrence After Primary
Radiotherapy: a Literature Review.
AB - PURPOSE OF REVIEW: While recurrence after primary treatment of prostate cancer
(PCa) is not uncommon, there is currently no consensus on the most appropriate
management after radiation treatment failure. This article seeks to explore the
currently utilized modalities for salvage treatment for radiorecurrent PCa. We
focused our review on the oncologic outcomes and reported toxicity rates in the
latest studies examining salvage radical prostatectomy (SRP), salvage cryotherapy
(SCT), salvage high-intensity focused ultrasound (HIFU) and re-irradiation.
RECENT FINDINGS: There does not appear to be any significant difference in
overall survival for more invasive salvage radical prostatectomy compared to the
minimally invasive salvage approaches. Additionally, there seems to be a trend
towards lower morbidity rates associated with minimally invasive and focal
salvage treatment. We are encouraged by the results presented in this review and
find that there is clearly a role for emerging minimally invasive and focal
therapies as durable options for salvage treatment in patients with
radiorecurrent PCa.
PMID- 28688022
TI - Mitral Valve Disease: a Comprehensive Review.
AB - PURPOSE OF REVIEW: This review aims to provide a comprehensive assessment of
mitral valve disease, both mitral stenosis and mitral regurgitation, starting
with an overview of the valve anatomy. RECENT FINDINGS: The advent of three
dimensional imaging has allowed a better representation of the valve anatomy.
Rheumatic disease is still the number one cause of mitral stenosis worldwide and
percutaneous balloon mitral valvuloplasty remains the therapy of choice when
indicated and in anatomically eligible patients. Mitral regurgitation (MR) is
classified as primary (i.e., lesion in the mitral apparatus) or secondary (caused
by left ventricular geometrical alterations). While surgery, preferably repair,
is still the recommended therapy for severe primary MR, percutaneous approaches
to repair and/or replace the mitral valve are being extensively investigated.
Mitral valve disease is common. A careful understanding of mitral valve anatomy
and the disease processes that affect the valve are crucial for providing optimal
patient care.
PMID- 28688023
TI - [PET-CT and PET-MRI of the prostate : From 18F-FDG to 68Ga-PSMA].
AB - CLINICAL/METHODICAL ISSUE: In the last few years nuclear medical diagnostics have
experienced a unprecedented renaissance in the diagnostics of prostate cancer,
due to the availability of hybrid imaging with positron emission tomography
computed tomography (PET/CT), PET magnetic resonance imaging (PET/MRI) and single
photon emission computed tomography (SPECT) CT as well as the development of
prostate-specific radiopharmaceuticals. METHODICAL INNOVATIONS: The use of
fluorodeoxyglucose (FDG), which has been successfully implemented for many years
in PET diagnostics, is only helpful in dedifferentiated tumors due to the
biological characteristics of prostate cancer. New specific radiopharmaceuticals,
such as choline-derivatives, which are incorporated into the prostate cancer cell
and built into the cell membrane as well as the recently developed highly
specific ligands for prostate-specific membrane antigen (PSMA) are
revolutionizing prostate cancer imaging and (re-) staging. PRACTICAL
RECOMMENDATIONS: The 68 Ga-labeled PSMA ligands for PET-CT and PET-MRI are highly
specific tracers for primary diagnostics and detection of metastases of prostate
carcinoma. In risk patients, which includes patients with intermediate and high
risk tumors, they have largely replaced choline-based PET-CT, especially in the
case of very low PSA values <0.5 ng/ml in the diagnostics of recurrence. The use
in the primary diagnostics as PET-MRI, also in combination with multiparametric
MRI (mpMRI), is promising with respect to early diagnostics and image fusion
assisted biopsy as well as surgery and irradiation planning.
PMID- 28688025
TI - Dyslipidemia and its Association with Meibomian Gland Dysfunction: A Systematic
Review.
AB - PURPOSE: To perform a systematic review of the literature examining the
association between meibomian gland dysfunction (MGD) and dyslipidemia. METHODS:
A systematic literature search was performed using the Medline database. A total
of four studies directly relevant to our search are reviewed here. RESULTS: In a
series of four studies, all but one found that the prevalence of dyslipidemia was
significantly higher in those with MGD compared to those without. Factors such as
age, total cholesterol, LDL, HDL, and triglycerides demonstrated a significant
association whereas sex, BMI, serum creatinine, and serum glucose did not.
Various subsets within the MGD group, such as males between the ages of 24-64,
were found to have higher total cholesterol levels compared to controls,
highlighting the association of dyslipidemia with sex and age. CONCLUSION: While
each study carried its own limitations preventing a causal relationship from
being established, it is evident that a strong positive correlation exists
between dyslipidemia and MGD. As such, eye care practitioners, through the
detection of MGD, may be identifying patients with dyslipidemia who were
previously believed to have normal serum lipid profiles. This may imply that eye
care providers have a role in detecting a well-known risk factor for
cardiovascular disease. Additionally, if prospective studies can demonstrate a
temporal relationship with MGD preceding dyslipidemia, clinicians could consider
lipid-lowering agents as management for both conditions.
PMID- 28688024
TI - An epidemiological investigation of age-related macular degeneration in aged
population in China: the Hainan study.
AB - PURPOSE: The aim of this study was to investigate the prevalence of age-related
macular degeneration (AMD) and the risk factors in the residents aged >=50 years
in Hainan Province. METHODS: Random sampling was carried out in four separated
cities in Hainan Province in 2015. All the subjects accomplished the standard
questionnaire and ocular examinations. The diagnosis of AMD was performed based
on the criteria proposed by Beckman Initiative for Macular Research
Classification Committee. RESULTS: Three hundred and fifty-seven subjects (15.6%)
were diagnosed with AMD, including 267 (11.7%) of early AMD, 64 (2.80%) of
intermediate AMD and 24 (1.1%) of late AMD, respectively. The factors associated
with the prevalence of AMD included age, educational level, smoking, outdoor
activities and diet. The prevalence of AMD increased with age, lower educational
level, smoking or less outdoor activities. The prevalence of AMD in those with a
diet of meat or eggs was higher compared with a diet of vegetables or fish. The
prevalence of early, intermediate and late AMD in the aged population in Hainan
Province was 11.7, 2.8 and 1.1%, respectively. CONCLUSIONS: Age and smoking were
the risk factors for AMD, while the educational level and outdoor activities were
the protective factors. Early AMD mostly occurred in those aged 50-59 years and
60-69 years, while intermediate and late AMD occurred in 70-79 years and older
than 80 years.
PMID- 28688026
TI - Indications and graft survival analysis in optical penetrating keratoplasty in a
tertiary care center in North India: a 5-year study.
AB - PURPOSE: To study the indications and variables correlating with graft survival
in optical penetrating keratoplasty in a tertiary care hospital in north India.
PARTICIPANTS: All patients who underwent optical keratoplasty, except those
undergoing lamellar grafts, tectonic grafts transplants and penetrating
keratoplasty done for therapeutic purposes were included in the study. Patients
with follow-up less than 2 years were excluded from the study. MATERIALS AND
METHODS: Data were obtained by reviewing the records of 101 patients who
underwent optical penetrating keratoplasty from 2008 to 2013 for various
indications. RESULTS: Out of 101 patients who underwent optical penetrating
keratoplasty, 71 were males and 30 were females. The mean age of the recipient
was 48.53 years with range 1-82 years. The main indications were previous failed
graft (29.7%), healed keratitis except HSV (15.8%), pseudophakic or aphakic
bullous keratopathy (14.8%), corneal dystrophies/degenerations (12.9%), adherent
leucoma (9.9%), post-HSV scars (8.9%), and others like anterior staphyloma,
congenital corneal opacities, buphthalmos and keratoconus (7.9%). The graft
survival rate was 67.33% at 1-year follow-up and 59.4% at 2-year follow-up. The
mean survival time of the grafts was 22.42 months. The mean time for graft
failure was 7.12 (+/-0.9) months. CONCLUSION: One- and 2-year survival of grafts
at our center is lower as compared to western studies, probably due to higher
percentage of poor prognosis indications for surgery and a relative scarcity of
excellent-quality donor corneas.
PMID- 28688028
TI - Novel Assessment of Interstitial Lung Disease Using the "Computer-Aided Lung
Informatics for Pathology Evaluation and Rating" (CALIPER) Software System in
Idiopathic Inflammatory Myopathies.
AB - PURPOSE: To evaluate the correlation between measurements from quantitative
thoracic high-resolution CT (HRCT) analysis with "Computer-Aided Lung Informatics
for Pathology Evaluation and Rating" (CALIPER) software and measurements from
pulmonary function tests (PFTs) in patients with idiopathic inflammatory
myopathies (IIM)-associated interstitial lung disease (ILD). METHODS: A cohort of
patients with IIM-associated ILD seen at Mayo Clinic was identified from medical
record review. Retrospective analysis of HRCT data and PFTs at baseline and 1
year was performed. The abnormalities in HRCT were quantified using CALIPER
software. RESULTS: A total of 110 patients were identified. At baseline, total
interstitial abnormalities as measured by CALIPER, both by absolute volume and by
percentage of total lung volume, had a significant negative correlation with
diffusing capacity for carbon monoxide (DLCO), total lung capacity (TLC), and
oxygen saturation. Analysis by subtype of interstitial abnormality revealed
significant negative correlations between ground glass opacities (GGO) and
reticular density (RD) with DLCO and TLC. At one year, changes of total
interstitial abnormalities compared with baseline had a significant negative
correlation with changes of TLC and oxygen saturation. A negative correlation
between changes of total interstitial abnormalities and DLCO was also observed,
but it was not statistically significant. Analysis by subtype of interstitial
abnormality revealed negative correlations between changes of GGO and RD and
changes of DLCO, TLC, and oxygen saturation, but most of the correlations did not
achieve statistical significance. CONCLUSION: CALIPER measurements correlate well
with functional measurements in patients with IIM-associated ILD.
PMID- 28688029
TI - Patterns of a Rectal Microbicide Placebo Gel Use in a Preparatory Stage for a
Phase I Trial Among Young Men Who Have Sex with Men.
AB - We examined young gay, bisexual, and other men who have sex with men's (YGBMSM)
usage patterns of a pre-coital, applicator-administered rectal placebo gel. An
ethnically diverse sample of 94 YGBMSM (aged 18-30 years) were asked to insert
hydroxyethylcellulose placebo gel rectally before receptive anal intercourse
(RAI) and report their gel use through an interactive voice response system
(IVRS) across 12 weeks. We used trajectory analyses to characterize participants'
use of the rectal gel over the 12 weeks, and examine whether these trajectories
varied based on participants' sociodemographic characteristics, sexual behaviors,
application and insertion behaviors, and experiences using the placebo gel. A
cubic model was the best fit for these longitudinal data, with two distinct
trajectories of gel use observed. The first trajectory ('High with Varying Gel
Use per Week') represented YGBMSM (N = 38; 40.3%) who reported using the rectal
gel on several occasions per week. The second trajectory ('Low and Consistent Gel
Use per Week') represented participants (N = 56; 59.7%) who reported a consistent
average use of one gel per week. Participants in the High with Varying Gel Use
Trajectory reported trying out a greater number of positions when inserting the
gel across the 12-weeks than peers in the Low and Consistent Gel Use Trajectory.
YGBMSM reporting more RAI occasions during the trial were more likely be present
in the High with Varying Gel Use Trajectory than peers in the Low and Consistent
Gel Use Trajectory. Future research examining how to facilitate gel application
and adherence among YGBMSM is merited.
PMID- 28688030
TI - From Pill to Condom, or Nothing at all: HIV Diagnosis and Discontinuation of
Highly Effective Contraceptives Among Women in Northeast Brazil.
AB - This is a cross-sectional study examining highly effective contraceptive (HEC)
use among HIV-positive women in Salvador, Brazil. We used multivariate logistic
regression to look for predictors of alternative contraceptive choices among
women who discontinued HEC after HIV diagnosis. Of 914 participants surveyed,
38.5% of participants used HEC before but not after diagnosis. Of these, 65.9%
used condoms alone; 19.3% used no protection; and 14.8% reported abstinence. Use
of condoms alone was associated with a history of other sexually transmitted
infections (AOR 2.18, 95% CI 1.09-4.66, p = 0.029). Abstinence was associated
with recent diagnosis (AOR 8.48, 95% CI 2.20-32.64, p = 0.002). Using no method
was associated with age below 25 (AOR 5.13, 95% CI 1.46-18.00, p = 0.011); income
below minimum wage (AOR 2.54, 95% CI 1.31-4.92, p = 0.006); HIV-positive partner
status (AOR 2.69, 95% CI 1.03-7.02, p = 0.043); and unknown partner status (AOR
2.90, 95% CI 1.04-8.05, p = 0.042). Improved contraceptive counseling is needed
after HIV diagnosis. Continuation of HEC should be encouraged for women wishing
to prevent pregnancy, and may increase contraceptive coverage among HIV-positive
women.
PMID- 28688031
TI - Remaining Gap in HIV Testing Uptake Among Female Sex Workers in Iran.
AB - We estimated the prevalence of recent HIV testing (i.e., having an HIV test
during the last 12 months and knew the results) among 1295 HIV-negative Iranian
female sex workers (FSW) in 2015. Overall, 70.4% (95% confidence intervals: 59.6,
79.3) of the participants reported a recent HIV testing. Concerns about their HIV
status (83.2%) was reported as the most common reason for HIV testing.
Incarceration history, having >5 paying partners, having >1 non-paying partner,
receiving harm reduction services, utilizing healthcare services, and knowing an
HIV testing site were significantly associated with recent HIV testing. In
contrast, outreach participants, having one non-paying sexual partner, and self
reported inconsistent condom use reduced the likelihood of recent HIV testing.
HIV testing uptake showed a ~2.5 times increase among FSW since 2010. While these
findings are promising and show improvement over a short period, HIV testing
programs should be expanded particularly through mobile and outreach efforts.
PMID- 28688032
TI - Prescription Opioid Use is Associated with Virologic Failure in People Living
with HIV.
AB - Prescription opioid misuse is a rising epidemic in the U.S., and people living
with HIV are at increased risk. We assessed the association between prescription
opioid use and virologic failure in HIV+ patients in the South Texas HIV Cohort.
We found prescription opioid use was significantly associated with virologic
failure, after adjustment for age, race, gender, insurance status, years living
with HIV, reported HIV risk factor, chronic hepatitis C virus infection, current
substance abuse, and care engagement. These findings suggest that opioid
analgesic use may have negative consequences beyond misuse in people living with
HIV.
PMID- 28688027
TI - Pharmacokinetics of Fentanyl and Its Derivatives in Children: A Comprehensive
Review.
AB - Fentanyl and its derivatives sufentanil, alfentanil, and remifentanil are potent
opioids. A comprehensive review of the use of fentanyl and its derivatives in the
pediatric population was performed using the National Library of Medicine PubMed.
Studies were included if they contained original pharmacokinetic parameters or
models using established routes of administration in patients younger than 18
years of age. Of 372 retrieved articles, 44 eligible pharmacokinetic studies
contained data of 821 patients younger than 18 years of age, including more than
46 preterm infants, 64 full-term neonates, 115 infants/toddlers, 188 children,
and 28 adolescents. Underlying diagnoses included congenital heart and pulmonary
disease and abdominal disorders. Routes of drug administration were intravenous,
epidural, oral-transmucosal, intranasal, and transdermal. Despite extensive use
in daily clinical practice, few studies have been performed. Preterm and term
infants have lower clearance and protein binding. Pharmacokinetics was not
altered by chronic renal or hepatic disease. Analyses of the pooled individual
patients' data revealed that clearance maturation relating to body weight could
be best described by the Hill function for sufentanil (R 2 = 0.71, B max 876
mL/min, K 50 16.3 kg) and alfentanil (R 2 = 0.70, B max (fixed) 420 mL/min, K 50
28 kg). The allometric exponent for estimation of clearance of sufentanil was
0.99 and 0.75 for alfentanil clearance. Maturation of remifentanil clearance was
described by linear regression to bodyweight (R 2 = 0.69). The allometric
exponent for estimation of remifentanil clearance was 0.76. For fentanyl, linear
regression showed only a weak correlation between clearance and bodyweight in
preterm and term neonates (R 2 = 0.22) owing to a lack of data in older age
groups. A large heterogeneity regarding study design, clinical setting, drug
administration, laboratory assays, and pharmacokinetic estimation was observed
between studies introducing bias into the analyses performed in this review. A
limitation of this review is that pharmacokinetic data, based on different modes
of administration, dosing schemes, and parameter estimation methods, were
combined.
PMID- 28688033
TI - First case of robotic laparoendoscopic single-site radical prostatectomy with
single-site VesPa platform.
AB - This study aimed at reporting our first experience with robotic laparoendoscopic
single-site radical prostatectomy (R-LESS-RP) with single-site VesPa platform
(Intuitive Surgical Inc.). A 68-year-old-man presenting with a cT1c
adenocarcinoma Gleason Score 3 + 4 = 7 in 4/12 bilateral cores underwent a
transperitoneal robotic LESS-RP with a single-site Vespa platform. Initial PSA,
prostate weight, and body mass index (BMI) were 4.4 ng/ml, 45 g, and 25,
respectively. Instruments and camera cross within the Single-Site port; the da
Vinci System software detects and reassigns the user's hands with the instruments
position. The single-site port is inserted through a 2-cm intraumbilical
incision. The robotic 8.5 mm scope and two surgical curved instruments
(fenestrated bipolar forceps and cautery hook) are introduced through the ports
and used for most of the procedure, whereas a wristed needle driver on the right
hand is used for the reconstructive steps. An additional 12 mm port (Air Seal,
SurgiQuest) is placed in a midline between the umbilicus and the right iliac
spine in order to facilitate table assistance during surgery and to place a drain
at the end of the procedure.Operative time and blood loss were 300 min and 400
mL, respectively. The postoperative course was uneventful. The drain and the
catheter were removed on days 1 and 6, respectively. The patient experienced a
temporary mild stress incontinence (one pad at sixth month) and erectile
dysfunction.Our first robotic laparoendoscopic single-site radical prostatectomy
(R-LESS-RP) with the single-site VesPa platform was associated with acceptable
operative times and perioperative outcome. This procedure is feasible without
complications, provided that a proper patient selection has occurred. Limited
movements together with the lack of the fourth robotic arm require a considerable
expertise in robotic surgery. Some tricks can help overcome technical
limitations. The Robotic LESS-RP reduces in some measure the limitations of
conventional LESS RP, although further refinement of the robotic instruments is
necessary.
PMID- 28688035
TI - Metformin Accelerates Glycolytic Lactate Production in Cultured Primary
Cerebellar Granule Neurons.
AB - Metformin is the most frequently used drug for the treatment of type-II diabetes.
As metformin has been reported to cross the blood-brain barrier, brain cells will
encounter this drug. To test whether metformin may affect the metabolism of
neurons, we exposed cultured rat cerebellar granule neurons to metformin.
Treatment with metformin caused a time- and concentration-dependent increase in
glycolytic lactate release from viable neurons as demonstrated by the three-to
fivefold increase in extracellular lactate concentration determined after
exposure to metformin. Half-maximal stimulation of lactate production was found
after incubation of neurons for 4 h with around 2 mM or for 24 h with around 0.5
mM metformin. Neuronal cell viability was not affected by millimolar
concentrations of metformin during acute incubations in the hour range nor during
prolonged incubations, although alterations in cell morphology were observed
during treatment with 10 mM metformin for days. The acute stimulation of neuronal
lactate release by metformin was persistent upon removal of metformin from the
medium and was not affected by the presence of modulators of adenosine
monophosphate activated kinase activity. In contrast, rabeprazole, an inhibitor
of the organic cation transporter 3, completely prevented metformin-mediated
stimulation of neuronal lactate production. In summary, the data presented
identify metformin as a potent stimulator of glycolytic lactate production in
viable cultured neurons and suggest that organic cation transporter 3 mediates
the uptake of metformin into neurons.
PMID- 28688034
TI - Preparation, Structure, and Potent Antifouling Activity of Sclerotioramine
Derivatives.
AB - A series of 30 sclerotioramine derivatives (2-31) of the natural compound, (+)
sclerotiorin (1), has been successfully semi-synthesized by a one-step reaction
with high yields (up to 80%). The structures of these new derivatives were
established by extensive spectroscopic methods and single-crystal X-ray
diffraction analysis for 3, 6, and 10. (+)-Sclerotiorin (1) and its semisynthetic
derivatives (2-31) were evaluated for their antifouling activity. Most of them
except 6, 7, 8, 12, and 28 showed potent antifouling activity against the larval
settlement of the barnacle Balanus amphitrite. More interestingly, most of the
aromatic amino-derivatives (13-17, 19-21, 23, 25-27, and 29-31) showed strong
antifouling activity; however, only two aliphatic amino-derivatives (5 and 10)
had the activity.
PMID- 28688036
TI - Carnitine/Organic Cation Transporter OCTN1 Negatively Regulates Activation in
Murine Cultured Microglial Cells.
AB - Brain immune cells, i.e., microglia, play an important role in the maintenance of
brain homeostasis, whereas chronic overactivation of microglia is involved in the
development of various neurodegenerative disorders. Therefore, the regulation of
microglial activation may contribute to their treatment. The aim of the present
study was to clarify the functional expression of carnitine/organic cation
transporter OCTN1/SLC22A4, which recognizes the naturally occurring food-derived
antioxidant ergothioneine (ERGO) as a substrate in vivo, in microglia and its
role in regulation of microglial activation. Primary cultured microglia derived
from wild-type mice (WT-microglia) and mouse microglial cell line BV2 exhibited
time-dependent uptake of [3H]- or d9-labeled ERGO. The uptake was markedly
decreased in cultured microglia from octn1 gene knockout mice (octn1 -/-
microglia) and BV2 cells transfected with small interfering RNA targeting the
mouse octn1 gene (siOCTN1). These results demonstrate that OCTN1 is functionally
expressed in murine microglial cells. Exposure of WT-microglia to ERGO led to a
significant decrease in cellular hypertrophy by LPS-stimulation with concomitant
attenuation of intracellular reactive oxygen species (ROS), suggesting that OCTN1
mediated ERGO uptake may suppress cellular hypertrophy via the inhibition of ROS
production with microglial activation. The expression of mRNA for interleukin
1beta (IL-1beta) after LPS-treatment was significantly increased in octn1 -/-
microglia and siOCTN1-treated BV2 cells compared to the control cells. Meanwhile,
treatment of ERGO minimally affected the induction of IL-1beta mRNA by LPS
stimulation in cultured microglia and BV2 cells. Thus, OCTN1 negatively regulated
the induction of inflammatory cytokine IL-1beta, at least in part, via the
transport of unidentified substrates other than ERGO in microglial cells.
PMID- 28688037
TI - Maize seed endophytic bacteria: dominance of antagonistic, lytic enzyme-producing
Bacillus spp.
AB - Beneficial aspects of endophytic microorganisms have motivated researchers to
explore plant endophytic world. The present study was aimed to isolate and
characterize the seed-borne endophytic bacteria from diverse maize genotypes.
Eighty maize seed endophytic bacteria (MSEB), isolated from 30 maize genotypes,
were characterized using polyphasic approach. The dendrograms and phylogenetic
tree generated on the basis of ARDRA analysis and metabolic profiling of
endophytic bacteria revealed genotypic and biochemical diversity among MSEB. The
16S rDNA sequence analysis revealed Bacillus as the most dominant encountered
genus affiliated with Phylum Firmicutes. Few isolates belonged to genus
Staphylococcus, whereas one isolate was identified as Corynebacterium sp. under
Phylum Actinobacteria. Majority of the MSEB isolates exhibited antagonism against
phytopathogenic fungi, production of ammonia, and secretion of lytic enzymes;
some isolates also exhibited indole acetic acid production, the traits of which
can be helpful in endophytic establishment and advantageous to the host plant.
Besides, many MSEB exhibited tolerance to salinity (10%), osmotic stress (40%
PEG6000), and temperature (60 degrees C), indicating their possible application
under stress conditions. Endophytic nature of the selected MSEB isolates was
confirmed by tracking their presence in shoots, leaves, and roots of the host
seedlings with the help of biochemical marker (rifampicin resistance). Thus, the
MSEB identified in the present study can be explored as potential bioinputs for
improving plant growth and productivity under stressed conditions, besides
helping in understanding the plant-endophyte interactions.
PMID- 28688041
TI - The Brand's PREACH Survey: A Capacity Assessment Tool for Predicting Readiness to
Engage African American Churches in Health.
AB - The purpose of this study was to develop the Brand's PREACH (Predicting Readiness
to Engage African American Churches in Health) Survey, a capacity assessment tool
based on the Brand's PREACH Model to predict the readiness of African American
(AA) churches to engage in health promotion programming (HPP). The survey
assessed church infrastructure (physical structure, personnel, funding, and
cultural/social support), frequency of HPP and readiness to engage in HPP. The
survey was administered to 108 AA churches in Illinois and North Carolina. The
study findings revealed that churches with more infrastructure tended to engage
in more HPP. Churches with less infrastructure tended to engage in less HPP.
Overall, infrastructure was associated with and able to predict the readiness of
AA churches to engage in HPP.
PMID- 28688038
TI - dAdd1 and dXNP prevent genome instability by maintaining HP1a localization at
Drosophila telomeres.
AB - Telomeres are important contributors to genome stability, as they prevent linear
chromosome end degradation and contribute to the avoidance of telomeric fusions.
An important component of the telomeres is the heterochromatin protein 1a (HP1a).
Mutations in Su(var)205, the gene encoding HP1a in Drosophila, result in
telomeric fusions, retrotransposon regulation loss and larger telomeres, leading
to chromosome instability. Previously, it was found that several proteins
physically interact with HP1a, including dXNP and dAdd1 (orthologues to the
mammalian ATRX gene). In this study, we found that mutations in the genes
encoding the dXNP and dAdd1 proteins affect chromosome stability, causing
chromosomal aberrations, including telomeric defects, similar to those observed
in Su(var)205 mutants. In somatic cells, we observed that dXNP and dAdd1
participate in the silencing of the telomeric HTT array of retrotransposons,
preventing anomalous retrotransposon transcription and integration. Furthermore,
the lack of dAdd1 results in the loss of HP1a from the telomeric regions without
affecting other chromosomal HP1a binding sites; mutations in dxnp also affected
HP1a localization but not at all telomeres, suggesting a specialized role for
dAdd1 and dXNP proteins in locating HP1a at the tips of the chromosomes. These
results place dAdd1 as an essential regulator of HP1a localization and function
in the telomere heterochromatic domain.
PMID- 28688040
TI - Identification of all homoeologous chromosomes of newly synthetic allotetraploid
Cucumis * hytivus and its wild parent reveals stable subgenome structure.
AB - Allopolyploidy and homoeologous recombination are two important processes in
reshaping genomes and generating evolutionary novelties. Newly formed
allopolyploids usually display chromosomal perturbations as a result of pairing
errors at meiosis. To understand mechanisms of stabilization of allopolyploid
species derived from distant chromosome bases, we investigated mitotic stability
of a synthetic Cucumis allotetraploid species in relation to meiosis chromosome
behavior. The Cucumis * hytivus is an allotetraploid synthesized from
interspecific hybridization between cucumber (Cucumis sativus, 2n = 14) and its
wild relative Cucumis hystrix (2n = 24) followed by spontaneous chromosome
doubling. In the present study, we analyzed the wild parent C. hystrix and the
latest generation of C. hytivus using GISH (genomic in situ hybridization) and
cross-species FISH (fluorescence in situ hybridization). The karyotype of C.
hystrix was constructed with two methods using cucumber fosmid clones and
repetitive sequences. Using repeat-element probe mix in two successive
hybridizations allowed for routine identification of all 19 homoeologous
chromosomes of allotetraploid C. hytivus. No aneuploids were identified in any C.
hytivus individuals that were characterized, and no large-scale chromosomal
rearrangements were identified in this synthetic allotetraploid. Meiotic
irregularities, such as homoeologous pairing, were frequently observed, resulting
in univalent and intergenomic multivalent formation. The relatively stable
chromosome structure of the synthetic Cucumis allotetraploid may be explained by
more deleterious chromosomal viable gametes compared with other allopolyploids.
The knowledge of genetic and genomic information of Cucumis allotetraploid
species could provide novel insights into the establishment of allopolyploids
with different chromosome bases.
PMID- 28688042
TI - Erratum to: Species-Specific Detection of Mycosphaerella polygoni-cuspidati as a
Biological Control Agent for Fallopia japonica by PCR Assay.
PMID- 28688039
TI - Using human artificial chromosomes to study centromere assembly and function.
AB - Centromeres are the site of assembly of the kinetochore, which directs chromosome
segregation during cell division. Active centromeres are characterized by the
presence of nucleosomes containing CENP-A and a specific chromatin environment
that resembles that of active genes. Recent work using human artificial
chromosomes (HAC) sheds light on the fine balance of different histone post
translational modifications and transcription that exists at centromeres for
kinetochore assembly and maintenance. Here, we review the use of HAC technology
to understand centromere assembly and function. We put particular emphasis on
studies using the alphoidtetO HAC, whose centromere can be specifically modified
for epigenetic engineering studies.
PMID- 28688043
TI - Characterization of the denitrifying bacterial community in a full-scale rockwool
biofilter for compost waste-gas treatment.
AB - The potential denitrification activity and the composition of the denitrifying
bacterial community in a full-scale rockwool biofilter used for treating
livestock manure composting emissions were analyzed. Packing material sampled
from the rockwool biofilter was anoxically batch-incubated with 15N-labeled
nitrate in the presence of different electron donors (compost extract, ammonium,
hydrogen sulfide, propionate, and acetate), and responses were compared with
those of activated sludge from a livestock wastewater treatment facility.
Overnight batch-incubation showed that potential denitrification activity for the
rockwool samples was higher with added compost extract than with other potential
electron donors. The number of 16S rRNA and nosZ genes in the rockwool samples
were in the range of 1.64-3.27 * 109 and 0.28-2.27 * 108 copies/g dry,
respectively. Denaturing gradient gel electrophoresis analysis targeting nirK,
nirS, and nosZ genes indicated that the distribution of nir genes was spread in a
vertical direction and the distribution of nosZ genes was spread horizontally
within the biofilter. The corresponding denitrifying enzymes were mainly related
to those from Phyllobacteriaceae, Bradyrhizobiaceae, and Alcaligenaceae bacteria
and to environmental clones retrieved from agricultural soil, activated sludge,
freshwater environments, and guts of earthworms or other invertebrates. A nosZ
gene fragment having 99% nucleotide sequence identity with that of Oligotropha
carboxidovorans was also detected. Some nirK fragments were related to NirK from
micro-aerobic environments. Thus, denitrification in this full-scale rockwool
biofilter might be achieved by a consortium of denitrifying bacteria adapted to
the intensely aerated ecosystem and utilizing mainly organic matter supplied by
the livestock manure composting waste-gas stream.
PMID- 28688045
TI - Erratum to: Enhancing the catalytic potential of nitrilase from Pseudomonas
putida for stereoselective nitrile hydrolysis.
PMID- 28688044
TI - Effects of mutation of Asn694 in Aspergillus niger alpha-glucosidase on
hydrolysis and transglucosylation.
AB - Aspergillus niger alpha-glucosidase (ANG), a member of glycoside hydrolase family
31, catalyzes hydrolysis of alpha-glucosidic linkages at the non-reducing end. In
the presence of high concentrations of maltose, the enzyme also catalyzes the
formation of alpha-(1->6)-glucosyl products by transglucosylation and it is used
for production of the industrially useful panose and isomaltooligosaccharides.
The initial transglucosylation by wild-type ANG in the presence of 100 mM maltose
[Glc(alpha1-4)Glc] yields both alpha-(1->6)- and alpha-(1->4)-glucosidic
linkages, the latter constituting ~25% of the total transfer reaction product.
The maltotriose [Glc(alpha1-4)Glc(alpha1-4)Glc], alpha-(1->4)-glucosyl product
disappears quickly, whereas the alpha-(1->6)-glucosyl products panose [Glc(alpha1
6)Glc(alpha1-4)Glc], isomaltose [Glc(alpha1-6)Glc], and isomaltotriose
[Glc(alpha1-6)Glc(alpha1-6)Glc] accumulate. To modify the transglucosylation
properties of ANG, residue Asn694, which was predicted to be involved in
formation of the plus subsites of ANG, was replaced with Ala, Leu, Phe, and Trp.
Except for N694A, the mutations enhanced the initial velocity of the alpha-(1->4)
transfer reaction to produce maltotriose, which was then degraded at a rate
similar to that by wild-type ANG. With increasing reaction time, N694F and N694W
mutations led to the accumulation of larger amounts of isomaltose and
isomaltotriose than achieved with the wild-type enzyme. In the final stage of the
reaction, the major product was panose (N694A and N694L) or isomaltose (N694F and
N694W).
PMID- 28688046
TI - [The Springer CME Award 2016 goes to diabetologist : Professor Juris J. Meier
receives prize for best continuing medical education article].
PMID- 28688047
TI - Assessment of Antioxidant and Antimicrobial Properties of Lignin from Corn Stover
Residue Pretreated with Low-Moisture Anhydrous Ammonia and Enzymatic Hydrolysis
Process.
AB - Lignin accounts for 15-35% of dry biomass materials. Therefore, developing value
added co-products from lignin residues is increasingly important to improve the
economic viability of biofuel production from biomass resources. The main
objective of this work was to study the lignin extracts from corn stover residue
obtained from a new and improved process for bioethanol production. Extraction
conditions that favored high lignin yield were optimized, and antioxidant and
antimicrobial activities of the resulting lignin were investigated. Potential
estrogenic toxicity of lignin extracts was also evaluated. The corn stover was
pretreated by low-moisture anhydrous ammonia (LMAA) and then subjected to
enzymatic hydrolysis using cellulase and hemicellulase. The residues were then
added with sodium hydroxide and extracted for different temperatures and times
for enhancing lignin yield and the bioactivities. The optimal extraction
conditions using 4% (w/v) sodium hydroxide were determined to be 50 degrees C,
120 min, and 1:8 (w:v), the ratio between corn stover solids and extracting
liquid. Under the optimal condition, 33.92 g of lignin yield per 100 g of corn
stover residue was obtained. Furthermore, the extracts produced using these
conditions showed the highest antioxidant activity by the hydrophilic oxygen
radical absorbance capacity (ORAC) assay. The extracts also displayed significant
antimicrobial activities against Listeria innocua. Minimal estrogenic impacts
were observed for all lignin extracts when tested using the MCF-7 cell
proliferation assay. Thus, the lignin extracts could be used for antioxidant and
antimicrobial applications, and improve the value of the co-products from the
biomass-based biorefinery.
PMID- 28688049
TI - Inter-relationship of serum leptin levels with selected anthropometric parameters
among a non-diabetic population: a cross-sectional study.
AB - PURPOSE: Association between serum leptin levels and anthropometric parameter is
well established in western countries according to the specific WHO cut-off
values assigned for those populations, whereas it is not clearly defined for
Asians especially with respect to gender. Thus, the objectives of this study were
to determine the relationship of serum leptin levels with body mass index (BMI),
waist circumference (WC), waist to hip ratio (WHR) to identify the variations of
serum leptin levels with gender and to evaluate the serum leptin levels in risk
and non-risk groups based on their anthropometric values. SUBJECTS/METHODS: A
cross-sectional study was carried out among 226 apparently healthy subjects (non
diabetics, age 20-70 years). Height, weight, WC, hip circumference (HC) and mid
arm circumference (MAC) were measured. BMI, WHR, waist to height ratio (WHtR)
were calculated. Fasting blood samples were collected. Serum leptin levels were
measured using human leptin ELISA kits. RESULTS: Majority of the participants
were females (59.3%). Serum leptin levels were significantly higher in females
(24.8 +/- 17.1 ng/mL) compared to males (9.3 +/- 7.9 ng/mL). Significant positive
correlations (P < 0.05) were observed between serum leptin levels and all
anthropometric parameters except height in both genders. The risk groups
according to BMI, WC and WHR in females were hyperleptinaemic and had
significantly (P < 0.05) higher serum leptin levels than the non-risk groups.
CONCLUSIONS: Linear trend was observed for serum leptin levels with weight, BMI,
WC, HC, WHR, MAC and WHtR in both genders. Though the serum leptin levels were
higher among risk groups, according to WHR, WC and BMI, the hyperleptinaemia was
observed only among females. LEVEL OF EVIDENCE: A descriptive cross-sectional
study, Level V.
PMID- 28688048
TI - Susceptibility background for type 2 diabetes in eleven Mexican Indigenous
populations: HNF4A gene analysis.
AB - The genetic risk of developing type 2 diabetes (T2D) increases in parallel with
the proportion of Native American ancestry. Mestizo Mexicans have a 70% Native
Amerindian genetic background. The T130I polymorphism in the HNF4A gene has been
associated with early-onset T2D in mestizo Mexicans. Thus, the aim of the present
study was to evaluate the frequency and relationship of the T130I variant in the
HNF4A gene with risk factors for developing T2D in eleven indigenous groups from
Mexico. In two groups, all exons of the HNF4A gene were directly sequenced; in
the remaining the T130I polymorphism was analyzed by restriction fragment length
polymorphism. Ancestry informative markers were assessed to confirm the
Amerindian component. An additional analysis of EHH was carried out.
Interestingly, HNF4A gene screening revealed only the presence of the T130I
polymorphism. The range frequency of the risk allele (T) in the indigenous groups
was from 2.7 to 16%. Genotypic frequencies (T130I/I130I) were higher and
significantly different from those of all of the populations included in the
HapMap Project (P < 0.005). EHH scores suggest a positive selection for T130I
polymorphism. Metabolic traits indicate a relationship between the T130I/I130I
genotypes with high triglyceride concentrations in the indigenous groups (P <
0.005). These results strongly suggest that the high frequency of the T130I
polymorphism and its biological relationship with dysfunction in lipid metabolism
in Mexican indigenous groups is a risk factor for the developing of T2D in
Mexicans.
PMID- 28688050
TI - Factor structure and reliability of the Multidimensional Body-Self Relations
Questionnaire in Chilean youth.
AB - The aim of this study was to ascertain the psychometric properties of the
Multidimensional Body-Self Relations Questionnaire (MBSRQ) for a sample of youth
in Chile. Cross-sectional survey was conducted with 451 participants. A non
clinical sample of adolescents and young adults between 15 and 25 years responded
the MBSRQ and a sociodemographic questionnaire. Factorial analysis identified
seven factors and provided empirical evidence that supports the use of these
factors to evaluate body perception in Chilean youth. Scores exhibited good
reliability in three factors (over 0.80) and acceptable reliability in the other
four (over 0.70). Findings suggest that the Spanish MBSRQ was psychometrically
sound, with 7 factors which are largely consistent with those identified in the
original version and validation study of this scale. These factors possess
sufficient internal consistency to make it plausible for use in research and
screening with Chilean youth, and potentially useful as an adjunctive measure in
the context of clinical decision making.
PMID- 28688051
TI - Transtubular excisional biopsy as a rescue for a non-diagnostic stereotactic
needle biopsy-case report and literature review.
AB - Stereotactic needle biopsy, a standard of care for acquiring deep-seated
pathology, has limitations and risks in some situations. We present an uncommon
case with basal ganglia dematiaceous mycetoma. Due to the firm consistency of the
lesion, the initial stereotactic needle biopsy failed to provide a diagnosis. In
a second operation, transtubular excisional biopsy was successfully performed to
remove the entire mycetoma. We reviewed recent case series of transtubular
approaches to deep-seated brain lesions and suggest this method could be a rescue
for a non-diagnostic stereotactic needle biopsy and even may be the approach of
choice in some cases.
PMID- 28688052
TI - Carboplatin plus weekly nanoparticle albumin-bound paclitaxel in elderly patients
with previously untreated advanced squamous non-small-cell lung cancer selected
based on Mini Nutritional Assessment short-form scores: a multicenter phase 2
study.
AB - PURPOSE: This multicenter, single-arm, open-label, phase 2 study assessed the
efficacy and safety of carboplatin plus weekly nanoparticle albumin-bound
paclitaxel in elderly patients with previously untreated advanced squamous non
small-cell lung cancer, selected based on the Mini Nutritional Assessment short
form scores (MNA-SF). METHODS: Patients received carboplatin (area under the
curve: 6) on Day 1, and nanoparticle albumin-bound paclitaxel (100 mg/m2) on Days
1, 8, and 15, every 28 days for <=4 cycles. Eligibility criteria included an MNA
SF score of >=8 points. The primary endpoint was the objective response rate.
RESULTS: Thirty patients with a median age of 76 (range 70-83) years were
enrolled. The objective response rate was 50.0% (95% confidence interval: 31.3
68.7%), which met the primary objective of this study. The disease control rate
was 73.3% (95% CI: 54.1-87.7%). At a median follow-up of 15.0 months, the median
progression-free and overall survival was 7.1 and 19.1 months, respectively. The
most common treatment-related adverse event of Grade >=3 was neutropenia (66.7%).
Non-hematological adverse events of Grade >=3 were minor. Well-nourished
patients, based on the MNA-SF, experienced fewer adverse events of Grade >=3
compared to patients at risk of malnutrition. All treatment-related adverse
events were tolerable and reversible. There were no treatment-related deaths.
CONCLUSIONS: Carboplatin plus weekly nanoparticle albumin-bound paclitaxel is
effective and well tolerated as a first-line treatment for elderly patients with
advanced squamous non-small-cell lung cancer. Eligibility based on MNA-SF
screening may be useful in determining acceptable toxicity.
PMID- 28688053
TI - Animal models of arrhythmogenic right ventricular cardiomyopathy: what have we
learned and where do we go? Insight for therapeutics.
AB - Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a rare genetically
determined cardiac heart muscle disorder characterized by fibro-fatty replacement
of the myocardium that results in heart failure and sudden cardiac death (SCD),
predominantly in young males. The disease is often caused by mutations in genes
encoding proteins of the desmosomal complex, with a significant minority caused
by mutations in non-desmosomal proteins. Existing treatment options are based on
SCD prevention with the implantable cardioverter defibrillator, antiarrhythmic
drugs, and anti-heart failure medication. Heart transplantation may also be
required and there is currently no cure. Several genetically modified animal
models have been developed to characterize the disease, assess its progression,
and determine the influence of potential environmental factors. These models have
also been very valuable for translational therapeutic approaches, to screen new
treatment options that prevent and/or reverse the disease. Here, we review the
available ARVC animal models reported to date, highlighting the most important
pathophysiological findings and discussing the effect of treatments tested so far
in this setting. We also describe gaps in our knowledge of the disease, with the
goal of stimulating research and improving patient outcomes.
PMID- 28688054
TI - Erratum to: Differential regulation of protein phosphatase 1 (PP1) isoforms in
human heart failure and atrial fibrillation.
PMID- 28688055
TI - Patterns of Change in Adolescent Dating Victimization and Aggression During
Middle School.
AB - Although mounting evidence suggests dating victimization and aggression begin in
early adolescence, little work has examined the pattern of these behaviors across
this age. This longitudinal study examined trajectories of dating victimization
and aggression across middle school using 12 waves of data. A sample of early
adolescents (N = 1369, 52.3% girls; 83% African American; 15% Hispanic or Latino)
residing in an urban, economically disadvantaged area participated in this study.
Youth completed measures of dating victimization and aggression quarterly across
the 3 years of middle school. Although results indicated a general trend of
increasing dating victimization and aggression across middle school, variation
existed for boys and girls. Specifically, girls showed increasing patterns of
both, whereas boys remained relatively stable across time. Dating victimization
and aggression were also highly correlated across time. These findings support
the implementation and refinement of prevention programming aimed at preventing
and reducing dating aggression and victimization in middle school.
PMID- 28688056
TI - Gene regulation of two ferredoxin:NADP+ oxidoreductases by the redox-responsive
regulator SurR in Thermococcus kodakarensis.
AB - The redox-responsive regulator SurR in the hyperthermophilic archaea Pyrococcus
furiosus and Thermococcus kodakarensis binds to the SurR-binding consensus
sequence (SBS) by responding to the presence of elemental sulfur. Here we
constructed a surR gene disruption strain (DTS) in T. kodakarensis, and
identified the genes that were under SurR control by comparing the transcriptomes
of DTS and parent strains. Among these genes, transcript levels of
ferredoxin:NADP+ oxidoreductases 1 and 2 (FNOR1 and FNOR2) genes displayed
opposite responses to surR deletion, indicating that SurR repressed FNOR1
transcription while enhancing FNOR2 transcription. Each promoter region contains
an SBS upstream (uSBS) and downstream (dSBS) of TATA. In addition to in vitro
binding assays, we examined the roles of each SBS in vivo. In FNOR1, mutations in
either one of the SBSs resulted in a complete loss of repression, indicating that
the presence of both SBSs was essential for repression. In FNOR2, uSBS indeed
functioned to enhance gene expression, whereas dSBS functioned in gene
repression. SurR bound to uSBS2 of FNOR2 more efficiently than to dSBS2 in vitro,
which may explain why SurR overall enhances FNOR2 transcription. Further analyses
indicated the importance in the distance between uSBS and TATA for
transcriptional activation in FNOR2.
PMID- 28688057
TI - Relatives' quality of life and psychological disturbance: a new concern of SLE
management.
AB - It is known that the quality of life (QOL) and psychological status of patients
with systemic lupus erythematosus (SLE) are severely impaired. However, a few
reports have assessed the QOL and psychological status in relatives of these
patients. This study aimed to assess the QOL and psychological status in
relatives of patients with SLE and their impact on patients. A total of 104
patient-relative dyads were evaluated using a 36-Item Short-Form Survey (SF-36),
Patient Health Questionnaire (PHQ-9), Generalized Anxiety Disorder Scale (GAD-7),
and Social Support Rating Scale (SSRS). Relatives of patients with SLE exhibited
an impaired QOL compared with the general population (69.59 +/- 22.78 vs 78.18 +/
15.88, P < 0.001) and suffered from depression (5.8 +/- 5.4) and anxiety (5.8 +/
6.0). GAD-7 of relatives was positively correlated with GAD-7 of patients (r =
0.210, P < 0.05). Patients reported a lower global SF-36 score when their
relatives had lower global SF-36 scores (50.13 +/- 19.18 vs 58.44 +/- 19.67, P <
0.05) and significantly higher SSRS when their relatives had lower PHQ-9 (41.9 +/
8.7 vs 36.3 +/- 6.2, P < 0.01) or GAD-7 scores (42.8 +/- 7.4 vs 36.7 +/- 6.6, P
< 0.01). The QOL and psychological status in relatives of patients with SLE were
adversely impaired. Associations exist between the QOL and psychological status
of relatives and patients with SLE. Therefore, both patients and their relatives
should be taken into account when making management decisions.
PMID- 28688059
TI - A Case of Severe, Refractory Hypotension After Amlodipine Overdose.
AB - Calcium channel blockers (CCBs) are responsible for a substantial portion of the
mortality associated with cardiovascular medication overdose cases. Amlodipine, a
dihydropyridine CCB, can cause prolonged hypotension in overdose. This report
describes a severe amlodipine overdose case that was refractory to multiple
therapeutic approaches. A 53-year-old male presented after ingesting eighty 10 mg
amlodipine tablets in a suicide attempt. The patient was initially managed with
calcium boluses, glucagon, multiple vasoactive agents, lipid emulsion infusions
and hyperinsulinemic euglycemic therapy. Methylene blue boluses were initiated
when hypotension persisted despite conventional treatments. Refractory
hypotension prompted the use of plasmapheresis in an attempt to lower serum
amlodipine levels. Finally, the patient was placed on extracorporeal membrane
oxygenation (ECMO) to maintain perfusion while the effects of the amlodipine
ingestion dissipated. Following an episode of asystole and pulseless electrical
activity prior to the start of ECMO, the patient suffered an anoxic brain injury
and suspected herniation prompting the family to withdraw medical care. There is
limited evidence in the literature describing the refractory treatment modalities
utilized in this patient. This report is unique as it describes the clinical
course of a patient when a multitude of unique treatments were combined.
PMID- 28688058
TI - A retrospective study of joint infections in patients with systemic lupus
erythematosus.
AB - The aim of this study was to analyze the clinical characteristics of systemic
lupus erythematosus (SLE) patients with joint infections. We retrospectively
reviewed the medical records of 11,734 SLE patients admitted to Peking Union
Medical College Hospital (PUMCH) from January 1990 to December 2016. Twenty
patients who developed joint infections were identified. Subjects without joint
infections (designated as control patients) were selected from the pool of SLE
patients using a 1:4 systematic sampling method. The median disease duration from
SLE onset to joint infection was 23 months (range 4 to 156 months). The symptoms
of patients with joint infections manifested as joint pain (all cases), swelling
(14 cases), and fever (15 cases). All patients had oligo-arthritis, and the knee
was the joint most commonly affected joint. There were 7 patients in the
Salmonella group and 5 in the Staphylococcus aureus group. One patient was
infected with Streptococcus, and 7 patients were infected with Mycobacterium. SLE
patients with and without joint infections demonstrated significant differences
(P < 0.05) regarding the following symptoms: pre-existing arthritis (65.0 vs
33.8%), gastrointestinal involvement (5.0 vs 26.3%), cardiac damage (5.0 vs
31.3%), elevated C-reactive protein (CRP) (80.0 vs 22.5%), and elevated SLE
Disease Activity Index (SLEDAI) score (>=5) (30.0 vs 77.5%). When an SLE patient
presents with pre-existing arthritis and suddenly develops asymmetric oligo- or
large-joint swelling and pain with elevated CRP levels and low disease activity,
joint infections should be considered. Early treatment could protect the joint
and improve functional outcomes.
PMID- 28688060
TI - Community-Based Study Recruitment of American Indian Cigarette Smokers and
Electronic Cigarette Users.
AB - Data on the effectiveness of strategies for the recruitment of American Indians
(AIs) into research is needed. This study describes and compares methods for
identifying and recruiting AI tobacco users into a pilot study. Community-based
strategies were used to recruit smokers (n = 35), e-cigarette users (n = 28), and
dual users (n = 32) of AI descent. Recruitment was considered proactive if study
staff contacted the individual at a pow wow, health fair, or vape shop and
participation on-site or reactive if the individual contacted the study staff and
participation occurred later. Screened, eligible, participated and costs and time
spent were compared with Chi square tests. To understand AI descent, the
relationship between number of AI grandparents and AI blood quantum was examined.
Number of participants screened via the proactive strategy was similar to the
reactive strategy (n = 84 vs. n = 82; p-value = 0.8766). A significantly greater
proportion of individuals screened via the proactive than the reactive strategy
were eligible (77 vs. 50%; p-value = 0.0002) and participated (75 vs. 39%; p
value = < 0.0001). Per participant cost and time estimated for the proactive
strategy was $89 and 87 min compared to $79 and 56 min for the reactive strategy.
Proportion at least half AI blood quantum was 32, 33, and 70% among those with 2,
3, and 4 AI grandparents, respectively (p = 0.0017). Proactive strategies
resulted in two-thirds of the sample, but required more resources than reactive
strategies. Overall, we found both strategies were feasible and resulted in the
ability to reach sample goals. Lastly, number of AI biological grandparents may
be a good, non-invasive indicator of AI blood quantum.
PMID- 28688061
TI - New method for correction of lumbo-sacral kyphosis deformity in patient with high
pelvic incidence.
AB - STUDY DESIGN: Technical note. OBJECTIVE: We describe a novel technique of
bilateral longitudinal sacral osteotomy allowing direct reduction of high pelvic
incidence (PI) and correction of sagittal imbalance. METHODS: A 25-year-old
female patient presented with a disabling lumbo-sacral kyphosis fused in situ
through previous operations with residual low-grade wound infection and grade IV
L5/S1 spondylolisthesis with severity index (SI) of 65%. A two-stage correction
was performed. First anterior in situ fixation of the L4-L5-S1 segments was
performed using a hollow modular anchorages (HMA) screw and L3/L4 anterior
interbody cage. The second stage consisted of instrumentation of the lower lumbar
spine and pelvis; placement of an S1 transverse K-wire as pivot point and
bilateral longitudinal sacral osteotomy which allowed for gradual retroversion of
the central sacrum relative to the pelvis. RESULTS: Sacrum was derotated by 30
degrees which allowed to restore spinal sagittal balance and decrease SI by 15%.
Postoperative recovery was complicated by a flare up of the pre-existing deep
wound infection. CONCLUSIONS: Bilateral longitudinal sacral osteotomy appears to
be a safe and efficient way of correcting the sagittal imbalance caused by an
extremely high PI. Although technically demanding, it achieves good radiological
and functional outcomes and avoids entering the spinal canal.
PMID- 28688062
TI - Giant thoracic discs: treatment, outcome, and follow-up of 33 patients in a
single centre.
AB - PURPOSE: To help guide treatment strategies and create insight into functional
outcomes in patients with Giant herniated thoracic discs (GHTD), which are
defined as occupying more than 40% of spinal canal. METHODS: Authors did a
retrospective analysis of prospective cohort of 33 cases of GHTD, using clinical
letters, notes, and telephonic questionnaires to determine their pre and
postoperative functional status, surgical details, and complication rates. 16
males and 17 females operated between 2006 and 2014 were included in the study. A
total of 23 patients underwent thoracotomy, 9 costotransversectomy, and 2
transpedicular approaches for excision of thoracic discs. Neuromonitoring was
used in seven patients. RESULTS: Frankel grade improved by 1 in 13 patients and
by 2 in 1 patient. One patient of T11/12 GHTD with neurogenic claudication
recovered completely, taking the overall improvement rate to 45.5%. It remained
static in 15 patients (45.5%) and deteriorated by 1 in 3 patients (9%). By mJOA
scoring too, the outcome was favorable in majority (84.4%) of patients. There
were three intraoperative complications (9%), which included two incidental
durotomies and one massive blood loss. Late postoperative complications were seen
in 12(39%) patients. They included intercostal neuralgia, mechanical pain around
costotransversectomy, progressive thoracic paraplegia due to spinal cord
herniation and residual disc fragments, reactive pleural effusion, CSF fistula
induced pleural effusion, and infective discitis. CONCLUSIONS: Surgery for giant
herniated thoracic disc has favorable outcome in majority (91%) of patients.
However, significant approach-related complications are to be anticipated in
patients undergoing thoracotomies, most of them being manageable. Author
recommends costotransversectomy, only in paracentral discs with smaller
percentage canal stenosis.
PMID- 28688063
TI - Spinal Cord Infarcts: Risk Factors, Management, and Prognosis.
AB - OPINION STATEMENT: There are no standard guidelines for treatment of spinal cord
ischemia due to how rare it is and the diverse etiology and presentations
involved. In addition, to date, there have been no large clinical trials
examining ideal pharmacologic treatment options for spinal cord infarct. In our
practice, we rely on hemodynamic augmentation initiated as soon as possible.
Otherwise, treatment is usually geared towards the etiology of spinal cord
ischemia. For instance, spinal cord ischemia occurring after aortic aneurysmal
repair may improve with CSF drainage through a lumbar catheter in the
periprocedural setting. Vertebral artery dissection should be treated with
antithrombotics. If no clear etiology is found and there is evidence of
atherosclerosis in other vascular beds, then management is focused on risk factor
modification with blood pressure and glucose control, statins, and
antithrombotics.
PMID- 28688064
TI - The death toll of French former prisoners.
AB - Several studies have documented that ex-prisoners are at higher risk of death
than the general population but only one study, concerning one single prison, has
examined the French case. This study relies on a nationally representative sample
of all inmates released from French prisons between June and December 2002. A
linkage between two administrative databases makes it possible to study mortality
within 5 years after release. The magnitude of ex-prisoners' excess mortality is
similar to that observed in other studies. The standardized mortality ratio is
3.6 (95% CI 3.1-4.1). Excess mortality after release is especially high between
the ages of 30 and 50. Inmates incarcerated for at least 5 years have lower risks
of dying (OR 0.4, 95% CI 0.2-0.9). We also find that adjusted sentences are
protective (OR 0.6, 95% CI 0.3-0.9).
PMID- 28688065
TI - Airway obstruction and the risk of myocardial infarction and death from coronary
heart disease: a national health examination survey with a 33-year follow-up
period.
AB - Chronic obstructive pulmonary disease (COPD) has been associated with coronary
mortality. Yet, data about the association between COPD and acute myocardial
infarction (MI) remain scarce. We aimed to study airway obstruction as a
predictor of MI and coronary mortality among 5576 Finnish adults who participated
in a national health examination survey between 1978 and 1980. Subjects underwent
spirometry, had all necessary data, showed no indications of cardiovascular
disease at baseline, and were followed up through record linkage with national
registers through 2011. The primary outcome consisted of a major coronary event
that is, hospitalization for MI or coronary death, whichever occurred first. We
specified obstruction using the lower limit of normal categorization. Through
multivariate analysis adjusted for potential confounding factors for coronary
heart disease, hazard ratios (HRs) (with the 95% confidence intervals in
parentheses) of a major coronary event, MI, and coronary death reached 1.06 (0.79
1.42), 0.84 (0.54-1.31), and 1.40 (1.04-1.88), respectively, in those with
obstruction compared to others. However, in women aged 30-49 obstruction appeared
to predict a major coronary event, where the adjusted HR reached 4.21 (1.73
10.28). In conclusion, obstruction appears to predict a major coronary event in
younger women only, whereas obstruction closely associates with the risk of
coronary death independent of sex and age.
PMID- 28688066
TI - Erratum to: An efficient cardiac mapping strategy for radiofrequency catheter
ablation with active learning.
PMID- 28688067
TI - Bioremediation of arsenic from water with citric acid cross-linked water hyacinth
(E. crassipes) root powder.
AB - A green and novel approach was demonstrated for successful remediation of arsenic
from contaminated water by citric acid (CA) cross-linked water hyacinth root
powder (RP). Different analytical techniques were used to investigate the binding
and structural properties of prepared materials. Titanium dioxide played a
significant role in the cross-linking process. Incorporation of CA into RP
enhanced its integrity, and thus removal efficiency remained unaffected after
several cyclic runs. Also the turbidity which formed due to treatment with
uncross-linked RP was reduced to below the permissible limit. Effect of the
amount of CA, material dose, treatment time, initial ion concentration, and pH
were investigated. Use of 10% (w/w) CA was found to be sufficient to bring down
the turbidity of the treated water below 2.5 nephelometric turbidity unit (NTU)
without hampering the removal capacity/rate. A material dose of 5 g/L removed
successfully total inorganic arsenic concentration to below 10 MUg/L. The
sorption process could be reasonably explained by Langmuir isotherm, and the
maximum adsorption capacity was found to be 28 MUg of arsenic/g. The material was
found to be more efficient at acidic pH (pHZPC = 6.72). The sorption process was
governed by a pseudo-second-order kinetic model.
PMID- 28688068
TI - Interpreting the deposition and vertical migration characteristics of 137Cs in
forest soil after the Fukushima Dai-ichi Nuclear Power Plant accident.
AB - We investigated the deposition and depth distributions of radiocesium in the
Takizawa Research Forest, Iwate Prefecture, in order to understand the behavior
of radionuclides released from the Fukushima Dai-ichi Nuclear Power Plant. The
deposition distribution and vertical depth distribution of radiocesium in the
soil were compared between topographically distinct parts of the forest where two
different tree species grow. The results for all investigated locations show that
almost 85% of the radiocesium has accumulated in the region of soil from the
topmost organic layer to a soil depth of 0-4 cm. However, no activity was
detected at depths greater than 20 cm. Analysis of the radiocesium deposition
patterns in forest locations dominated by either coniferous or deciduous tree
species suggests that radiocesium was sequestered and retained in higher
concentrations in coniferous areas. The deposition data showed large spatial
variability, reflecting the differences in tree species and topography. The
variations in the measured 137Cs concentrations reflected the variability in the
characteristics of the forest floor environment and the heterogeneity of the
initial ground-deposition of the Fukushima fallout. Sequential extraction
experiments showed that most of the 137Cs was present in an un-exchangeable form
with weak mobility. Nevertheless, the post-vertical distribution of 137Cs is
expected to be governed by the percentage of exchangeable 137Cs in the organic
layer and the organic-rich upper soil horizons.
PMID- 28688069
TI - Shoreline change assessment using multi-temporal satellite images: a case study
of Lake Sapanca, NW Turkey.
AB - The research summarized here determines historical shoreline changes along Lake
Sapanca by using Remote Sensing (RS) and Geographical Information Systems (GIS).
Six multi-temporal satellite images of Landsat Multispectral Scanner (L1-5 MMS),
Enhanced Thematic Mapper Plus (L7 ETM+), and Operational Land Imager Sensors (L8
OLI), covering the period between 17 June 1975 and 15 July 2016, were used to
monitor shoreline positions and estimate change rates along the coastal zone.
After pre-possessing routines, the Normalized Difference Water Index (NDWI),
Modified Normalized Difference Water Index (MNDWI), and supervised classification
techniques were utilized to extract six different shorelines. Digital Shoreline
Analysis System (DSAS), a toolbox that enables transect-based computations of
shoreline displacement, was used to compute historical shoreline change rates.
The average rate of shoreline change for the entire cost was 2.7 m/year of
progradation with an uncertainty of 0.2 m/year. While the great part of the lake
shoreline remained stable, the study concluded that the easterly and westerly
coasts and deltaic coasts are more vulnerable to shoreline displacements over the
last four decades. The study also reveals that anthropogenic activities, more
specifically over extraction of freshwater from the lake, cyclic variation in
rainfall, and deposition of sediment transported by the surrounding creeks
dominantly control spatiotemporal shoreline changes in the region. Monitoring
shoreline changes using multi-temporal satellite images is a significant
component for the coastal decision-making and management.
PMID- 28688070
TI - Long term performance of porous platinum coated neural electrodes.
AB - Over the last several years, there has been a growing interest in neural implants
for the study and diagnostics of neurological disorders as well as for the
symptomatic treatment of central nervous system related diseases. One of the
major challenges is the trade-off between small electrode sizes for high
selectivity between single neurons and large electrode-tissue interface areas for
excellent stimulation and recording properties. This paper presents an approach
of increasing the real surface area of the electrodes by creating a surface
microstructure. Two major novelties let this work stand out from existing
approaches which mainly make use of porous coatings such as platinum black or
iridium oxide, or Poly(3,4-ethylenedioxythiophene) (PEDOT). Roughening is carried
out by a dry etching process on the silicon electrode core before being coated by
a sputtered platinum layer, eliminating complicated deposition processes as for
the materials described above. The technology is compatible with any commonly
used coating material. In addition, the surface roughening is compatible with
high aspect ratio penetrating electrode arrays such as the well-established Utah
electrode array, whose unique geometry presents a challenge in the surface
modification of active electrode sites. The dry etching process is well
characterized and yields a high controllability of pore size and depth. This
paper confirms the superior electrochemical properties including impedance,
charge injection capacity, and charge storage capacity of surface engineered
electrode arrays compared to conventional arrays over a period of 12 weeks.
Furthermore, mechanical stability of the modified electrodes was tested by
implantation in the brain of a recently deceased rat. In conclusion, the larger
interface surface of the electrodes does not only decrease the impedance which
should lead to enhanced Signal to noise ratio (SNR) for recording purposes, but
also yields higher charge injection capacities, which improve the stimulation
characteristics of the implants.
PMID- 28688071
TI - Study of the behavior of Euglena viridis, Euglena gracilis and Lepadella patella
cultured in all-glass microaquarium.
AB - In the paper, the microaquarium fabricated in a form of entirely glass lab-on-a
chip for culturing and microscale study of microorganisms has been presented. A
new approach towards cellular studies that brings a significant improvement over
commonly utilized - polymer-based solutions has been shown. For the first time,
all-borosilicate glass chip was applied for the culturing of the selected
microorganisms and enabled notable population growth and behaviorism
investigation. The chip fabrication method in comparison to typical glass chip
technology was notably simplified, including quick patterning and low temperature
bonding in 80 degrees C. In the studies, both a single-cell (Euglena gracilis
and Euglena viridis) and multi-cell microorganisms (Lepadella patella) were
cultured in the microaquarium. Behaviorism of the selected microorganisms was
investigated by supplying various proportions of carbon dioxide, nitrogen and air
into the chip. Tests included studies of microorganisms chemotaxis, viability
(mostly based on photosynthesis process) and coexistence in the lab-on-a-chip
environment. The experiments confirmed that the developed chip is a tool that
fits the requirements for the culturing and behavioral studies of microorganisms
and constitute ground-works to propel its further application in broadly defined
cellular study field.
PMID- 28688072
TI - [A qualitative exploration of the chronic use of psychotropic drugs in nursing
homes].
AB - BACKGROUND: Although guidelines put forward non-pharmacological therapies and
advise against the chronic use of psychotropic drugs, these are still being
prescribed regularly in Belgian nursing homes. GOAL: To explore the reasons for
initiation, continuation and cessation of psychotropic drug treatment of elderly
with dementia and behavioral problems, residing in the nursing home. METHOD:
Twenty-seven interviews from an earlier project were used, in which a semi
structured interview was conducted with the nursing staff, the physicians and the
caretakers of eleven randomly selected residents from three nursing homes. A
qualitative analysis was performed by three independent researchers according to
'The Qualitative Analysis Guide of Leuven (QUAGOL)'. A first analysis focused on
the process of initiation, continuation and cessation of medication. A second
analysis compared the different participants of each interview and looked for
similarities and differences. RESULTS: Seventeen codes were developed for four
themes: (1) To initiate, to continue or to cease?; (2) Behavior; (3) Therapy; and
(4) Alternatives. The reasons for initiating psychotropic drugs were reducing
disruptive behavior and improving the quality of life of the resident. A
comparison between the interviewed showed that psychotropic drugs were initiated
at the request of the nursing staff. Neither doctors nor nurses considered the
monitoring of the drug therapy their task, and tended to pass on this
responsibility. Once psychotropic drugs were started, the treatment was chronic
but remained part of a dynamic process in which a balance was sought between
benefits and adverse effects. More insights into the behavior of the resident led
to a better treatment of the behavioral problems. CONCLUSION: Nurses play an
important role in the initiation and continuation of psychotropic drugs.
Physicians should take a more active role in the process of indication and
monitoring of psychopharmaceuticals. Discontinuation of psychotropic drugs and
the use of non-pharmacological alternatives are important bottlenecks in nursing
homes. Education and training, updated practice guidelines, appropriate research,
professionalization and management elements can, in a complex interaction, change
this situation for the better.
PMID- 28688073
TI - The Integration of Occlusion and Disparity Information for Judging Depth in
Autism Spectrum Disorder.
AB - In autism spectrum disorder (ASD), atypical integration of visual depth cues may
be due to flattened perceptual priors or selective fusion. The current study
attempts to disentangle these explanations by psychophysically assessing within
modality integration of ordinal (occlusion) and metric (disparity) depth cues
while accounting for sensitivity to stereoscopic information. Participants
included 22 individuals with ASD and 23 typically developing matched controls.
Although adults with ASD were found to have significantly poorer stereoacuity,
they were still able to automatically integrate conflicting depth cues, lending
support to the idea that priors are intact in ASD. However, dissimilarities in
response speed variability between the ASD and TD groups suggests that there may
be differences in the perceptual decision-making aspect of the task.
PMID- 28688074
TI - Teaching Reading Comprehension Skills to a Child with Autism Using Behaviour
Skills Training.
AB - A multiple probe design across skills was used to examine the effects of
behaviour skills training (BST) on teaching four reading comprehension skills
(predicting, questioning, clarifying, and summarizing) to a 7th grade student
with autism. Following baseline, the student received 12 sessions of BST during
which each skill was taught to criterion. At each session, data was also
collected on the accuracy of oral responses to 10 comprehension questions. BST
was associated with clear gains in the participant's performance on each
comprehension skill, along with concomitant gains in reading comprehension both
on the daily probes and a standardized measure. Skills maintained at follow-up
support the conclusion that BST was effective in improving the comprehension
skills of a child with autism.
PMID- 28688075
TI - Coparenting Competence in Parents of Children with ASD: A Marker of Coparenting
Quality.
AB - The coparenting relationship has been linked to parenting stress, parenting self
efficacy and many other concerns associated with the development of children with
ASD. Parents of children with ASD (N = 22) were interviewed to explore three
domains of their coparenting relationship; (1) adaptation to the emergence of
their child's autism, (2) parenting their child with ASD, (3) expectations for
their child's developmental outcomes. The concept of coparenting competence,
developed during analysis, describes collective perceptions of parenting
efficacy. Parents linked perceptions of coparenting competence to their, ability
to cope with diagnosis and parenting, motivation to do what they could for their
child, and hopes for their child's development. The concept of coparenting
competence could play an important role in future research and intervention.
PMID- 28688076
TI - An Eye-Movement Study of relational Memory in Adults with Autism Spectrum
Disorder.
AB - Persons with Autism Spectrum Disorder (ASD) demonstrate good memory for single
items but difficulties remembering contextual information related to these items.
Recently, we found compromised explicit but intact implicit retrieval of object
location information in ASD (Ring et al. Autism Res 8(5):609-619, 2015). Eye
movement data collected from a sub-sample of the participants are the focus of
the current paper. At encoding, trial-by-trial viewing durations predicted
subsequent retrieval success only in typically developing (TD) participants.
During retrieval, TD compared to ASD participants looked significantly longer at
previously studied object-locations compared to alternative locations. These
findings extend similar observations recently reported by Cooper et al.
(Cognition 159:127-138, 2017a) and demonstrate that eye-movement data can shed
important light on the source and nature of relational memory difficulties in
ASD.
PMID- 28688077
TI - Grandparents' Experience of Autism Spectrum Disorder: Identifying Primary Themes
and Needs.
AB - Limited information is available regarding the first person perspective of
grandparents of children with Autism Spectrum Disorders (ASD). In the present
study, 1870 grandparents of a child with ASD participated in a nationwide,
online, anonymous, 30-minute survey and responded to open-ended questions
including their "greatest challenges and greatest joys" as the grandparent of a
child on the autism spectrum. A grounded theory approach to qualitative analysis
revealed four overarching categories: a Desire for Connection, Barriers to Care,
Celebration of Progress, and Personal Reactions. Despite the presence of
significant challenges grandparents often experienced positivity in their role,
and engaged in radical acceptance of their grandchild as well as transformative
insight and advocacy. Specific recommendations are offered to help address
grandparents' needs and capitalize upon their resilience.
PMID- 28688078
TI - Differences in Neural Correlates of Speech Perception in 3 Month Olds at High and
Low Risk for Autism Spectrum Disorder.
AB - In this study, we investigated neural precursors of language acquisition as
potential endophenotypes of autism spectrum disorder (ASD) in 3-month-old infants
at high and low familial ASD risk. Infants were imaged using functional near
infrared spectroscopy while they listened to auditory stimuli containing syllable
repetitions; their neural responses were analyzed over left and right temporal
regions. While female low risk infants showed initial neural activation that
decreased over exposure to repetition-based stimuli, potentially indicating a
habituation response to repetition in speech, female high risk infants showed no
changes in neural activity over exposure. This finding may indicate a potential
neural endophenotype of language development or ASD specific to females at risk
for the disorder.
PMID- 28688079
TI - Self-perceived care needs in older adults with joint pain and comorbidity.
AB - BACKGROUND: The aim of this study was to explore self-perceived care needs and
determinants of identified needs in older adults with joint pain and comorbidity.
METHODS: This is a cross-sectional study using baseline data from a cohort study
of older adults in the Netherlands (>=65 years) with joint pain and comorbidity
(n = 407). We used the Camberwell Assessment of Need for the Elderly (CANE) to
assess self-perceived care needs. Regression analyses were conducted to examine
the associations between needs and sociodemographic factors (age, gender, partner
status and educational level), physical factors (pain intensity, comorbidity,
frailty and physical functioning) and psychosocial factors (anxiety, depression
and social support). RESULTS: Older adults with joint pain and comorbidity
reported on average 4.0 care needs out of 13 CANE items, of which 0.3 were unmet.
High levels of environmental and physical needs were reported, such as needs with
regard to physical illness (91%), household (61%) and mobility/falls (53%).
However, most of these needs were met. Only few people reported psychosocial
needs, but a large proportion of these needs was unmet, especially regarding
company (66.7%) and daytime activities (37%). Psychosocial needs were more often
present in frail participants (OR 2.40, 95% CI 1.25-4.61), and those with less
perceived social support (OR 1.05, 95% CI 1.01-1.08) and more depressive symptoms
(OR 1.17, 95% CI 1.07-1.26). DISCUSSION/CONCLUSIONS: Unmet needs are mainly
present in the psychosocial domain. Specific attention targeted at these unmet
needs may improve psychosocial well-being of older adults with joint pain and
comorbidity.
PMID- 28688080
TI - The Italian version of the "frailty index" based on deficits in health: a
validation study.
AB - BACKGROUND AND AIM: Several measurements were taken for frailty classification in
geriatric population. "Frailty index" is based on "deficits in health," but it is
still not available in Italian version. Thus, the aim of the present work was to
validate a version of "frailty index" for the Italian geriatric community.
METHODS: The validation of Italian frailty index (IFi) is based on a cohort study
that enrolled 1077 non-disabled outpatients aged 65 years or older (81.3 +/- 6.5
years) in Naples (Italy). IFi has been expressed as a ratio of deficits
present/deficits considered after a comprehensive geriatric assessment. IFi was
stratified in light, moderate and severe frailty. Mortality, disability
(considering an increase in ADL lost >=1 from the baseline) and hospitalization
were considered at 3, 6, 12, 18 and 24 months of follow-up. Area under curve
(AUC) was evaluated for both Fried's and IFi frailty index. RESULT: At the end of
follow-up, mortality increased from 1.0 to 30.3%, disability from 40.9 to 92.3%
and hospitalization from 0.0 to 59.0% (p < 0.001 for trend). Multivariate
analysis shows that the relative risk for unit increase in IFi is 1.09 (95% CI =
1.01-1.17, p = 0.013) for mortality, 1.04 (95% CI = 1.01-1.06, p = 0.024) for
disability and 1.03 (95% CI = 1.01-1.07, p = 0.041) for hospitalization. AUC is
higher in IFi with respect to Fried's frailty index when considering mortality
(0.809 vs. 0.658, respectively), disability (0.800 vs. 0.729, respectively) and
hospitalization (0.707 vs. 0.646, respectively). CONCLUSIONS: IFi is a valid
measure of frailty after the comprehensive geriatric assessment in an Italian
cohort of non-institutionalized patients.
PMID- 28688081
TI - Collaborative operation with cardiovascular surgeons in general thoracic surgery.
AB - OBJECTIVES: The aim of this study was to investigate the feasibility and safety
of our surgical experiences conducted in collaboration with cardiovascular
surgeons at our institution. METHODS: From May 2002 to December 2015, among 3595
general thoracic surgeries, 75 (2.1%) operations were carried out collaboratively
with cardiovascular surgeons at Nagoya University Hospital. We investigated the
surgical procedures, manipulated organs, morbidity and mortality, completeness of
surgical resection, and prognosis of these 75 cases. RESULTS: The study cohort
consisted of 56 males and 19 females, ranging in age from 18 to 79 years (median
60 years). Fifty-eight patients had a malignant disease, and 17 had a benign
disease. Out of 75 collaborative surgeries, 53 (71%) were scheduled cases
(cardiovascular surgeons' support was considered to be necessary preoperatively),
and 22 (29%) were emergent cases (cardiovascular surgeons' support was considered
to be necessary intraoperatively). No 30- or 90-day mortality was observed.
Respiratory failure, defined as the requirement of mechanical ventilation or non
invasive positive pressure ventilation for >=5 days, was the most common
morbidity (n = 14, 18%). Forty-three patients (78%) out of 55 with thoracic
neoplasms achieved microscopic complete resection. The resection status of the
remaining 12 (22%) was microscopic residual tumor. CONCLUSION: Collaborative
surgeries with cardiovascular surgeons at our institution were feasible. High
quality surgeries with a good balance between safety and completeness of
resection are important not only for treatment, but also in terms of education
for general thoracic surgeons.
PMID- 28688082
TI - Circulating myeloid-derived suppressor cells increase in patients undergoing neo
adjuvant chemotherapy for breast cancer.
AB - This study sought to evaluate whether myeloid-derived suppressor cells (MDSC)
could be affected by chemotherapy and correlate with pathologic complete response
(pCR) in breast cancer patients receiving neo-adjuvant chemotherapy. Peripheral
blood levels of granulocytic (G-MDSC) and monocytic (M-MDSC) MDSC were measured
by flow cytometry prior to cycle 1 and 2 of doxorubicin and cyclophosphamide and
1st and last administration of paclitaxel or paclitaxel/anti-HER2 therapy. Of 24
patients, 11, 6 and 7 patients were triple negative, HER2+ and hormone receptor+,
respectively. 45.8% had pCR. Mean M-MDSC% were <1. Mean G-MDSC% and 95%
confidence intervals were 0.88 (0.23-1.54), 5.07 (2.45-7.69), 9.32 (4.02-14.61)
and 1.97 (0.53-3.41) at draws 1-4. The increase in G-MDSC by draw 3 was
significant (p < 0.0001) in all breast cancer types. G-MDSC levels at the last
draw were numerically lower in patients with pCR (1.15; 95% CI 0.14-2.16) versus
patients with no pCR (2.71; 95% CI 0-5.47). There was no significant rise in G
MDSC from draw 1 to 3 in African American patients, and at draw 3 G-MDSC levels
were significantly lower in African Americans versus Caucasians (p < 0.05). It
was concluded that G-MDSC% increased during doxorubicin and cyclophosphamide
therapy, but did not significantly differ between patients based on pathologic
complete response.
PMID- 28688083
TI - The SWI/SNF chromatin-remodeling factors BAF60a, b, and c in nutrient signaling
and metabolic control.
AB - Metabolic syndrome has become a global epidemic that adversely affects human
health. Both genetic and environmental factors contribute to the pathogenesis of
metabolic disorders; however, the mechanisms that integrate these cues to
regulate metabolic physiology and the development of metabolic disorders remain
incompletely defined. Emerging evidence suggests that SWI/SNF chromatin
remodeling complexes are critical for directing metabolic reprogramming and
adaptation in response to nutritional and other physiological signals. The ATP
dependent SWI/SNF chromatin-remodeling complexes comprise up to 11 subunits,
among which the BAF60 subunit serves as a key link between the core complexes and
specific transcriptional factors. The BAF60 subunit has three members, BAF60a, b,
and c. The distinct tissue distribution patterns and regulatory mechanisms of
BAF60 proteins confer each isoform with specialized functions in different
metabolic cell types. In this review, we summarize the emerging roles and
mechanisms of BAF60 proteins in the regulation of nutrient sensing and energy
metabolism under physiological and disease conditions.
PMID- 28688085
TI - Fit for purpose and modern validity theory in clinical outcomes assessment.
AB - PURPOSE: The US Food and Drug Administration (FDA), as part of its regulatory
mission, is charged with determining whether a clinical outcome assessment (COA)
is "fit for purpose" when used in clinical trials to support drug approval and
product labeling. In this paper, we will provide a review (and some commentary)
on the current state of affairs in COA development/evaluation/use with a focus on
one aspect: How do you know you are measuring the right thing? In the
psychometric literature, this concept is referred to broadly as validity and has
itself evolved over many years of research and application. REVIEW: After a brief
introduction, the first section will review current ideas about "fit for purpose"
and how it has been viewed by FDA. This section will also describe some of the
unique challenges to COA development/evaluation/use in the clinical trials space.
Following this, we provide an overview of modern validity theory as it is
currently understood in the psychometric tradition. This overview will focus
primarily on the perspective of validity theorists such as Messick and Kane whose
work forms the backbone for the bulk of high-stakes assessment in areas such as
education, psychology, and health outcomes. CONCLUSIONS: We situate the concept
of fit for purpose within the broader context of validity. By comparing and
contrasting the approaches and the situations where they have traditionally been
applied, we identify areas of conceptual overlap as well as areas where more
discussion and research are needed.
PMID- 28688084
TI - Chemical proteomic analysis of 6-benzylaminopurine molecular partners in wheat
grains.
AB - KEY MESSAGE: An affinity-based chemical proteomic technique enabled direct
identification of BAP-interacting proteins in wheat, including the well-known
cytokinin-binder, cytokinin-binding protein 1. In this work, we show the
development of a chemical proteomic technique for the identification of proteins
binding to natural aromatic cytokinins (CKs). 6-benzylaminopurine (BAP) and
documented CK-binder, wheat germ-allocated cytokinin-binding protein 1 (CBP-1),
were suggested as an ideal proof-of concept affinity pair. Therefore, wheat
grains were chosen as a model plant material. The BAP affinity beads were
prepared by the immobilization of synthesized BAP-derived ligand to a commercial,
pre-activated resin and used to isolate target proteins. The proteomic analysis
of complex plant extracts is often complicated by the presence of highly abundant
background proteins; in this case, the omnipresent alpha-amylase inhibitors
(AAIs). To cope with this problem, we included SDS-PAGE, in-gel trypsin digestion
and fraction pooling prior to shotgun analysis, which brought about an obvious
drop in the signals belonging to the obstructing proteins. This was accompanied
by a sharp increase in the number of identified BAP targets in comparison to a
conventional in-solution digestion approach. To distinguish specific CK-binding
proteins from those having a general affinity for nucleotide-like compounds,
competitive pull-downs with natural nucleotides and free BAP were included in
every affinity experiment. By this approach, we were able to identify a group of
BAP-interacting proteins, which were subsequently found to be related to
biological processes affected by CKs. Moreover, the selected affinity enrichment
strategy was verified by the detection of the aforementioned CK-interacting
protein, CBP-1. We propose that the developed method represents a promising tool
for appealing research of as yet unknown CK molecular partners in plants.
PMID- 28688086
TI - Sequencing the Biology of Entry: The Retroviral env Gene.
AB - The surface envelope protein of any virus is major determinant of the host cell
that is infected and as a result a major determinant of viral pathogenesis.
Retroviruses have a single surface protein named Env. It is a trimer of
heterodimers and is responsible for binding to the host cell receptor and
mediating fusion between the viral and host membranes. In this review we will
discuss the history of the discovery of the avian leukosis virus (ALV) and human
immunodeficiency virus type 1 (HIV-1) Env proteins and their receptor
specificity, comparing the many differences but having some similarities. Much of
the progress in these fields has relied on viral genetics and genetic
polymorphisms in the host population. A special feature of HIV-1 is that its
persistent infection in its human host, to the point of depleting its favorite
target cells, allows the virus to evolve new entry phenotypes to expand its host
range into several new cell types. This variety of entry phenotypes has led to
confusion in the field leading to the major form of entry phenotype of HIV-1
being overlooked until recently. Thus an important part of this story is the
description and naming of the most abundant entry form of the virus: R5 T cell
tropic HIV-1.
PMID- 28688087
TI - Roles of Pro-viral Host Factors in Mosquito-Borne Flavivirus Infections.
AB - Identification and analysis of viral host factors is a growing area of research
which aims to understand the how viruses molecularly interface with the host
cell. Investigations into flavivirus-host interactions has led to new discoveries
in viral and cell biology, and will potentially bolster strategies to control the
important diseases caused by these pathogens. Here, we address the current
knowledge of prominent host factors required for the flavivirus life-cycle and
mechanisms by which they promote infection.
PMID- 28688088
TI - Early stimulated thyroglobulin for response prediction after recombinant human
thyrotropin-aided radioiodine therapy.
AB - OBJECTIVE: Measurement of recombinant human thyrotropin (rhTSH)-stimulated
thyroglobulin (Tg) is generally recommended 72 h after the second rhTSH
injection. However, due to the acute effect of I-131 on thyrocytes, Tg measured
after radioiodine therapy (RIT) would not accurately reflect the thyroid tissue
burden. We aimed to determine predictive values of serum Tg level measured just
before rhTSH-aided RIT and to compare the results obtained just after RIT in
patients with differentiated thyroid carcinoma (DTC). METHODS: We evaluated 150
patients with DTC who underwent rhTSH-aided RIT (2.96-6.66 GBq) after total
thyroidectomy between 2009 and 2014. Serum Tg level was measured 24 h (early Tg)
and 72 (or 96) h (delayed Tg) after the second rhTSH injection. An excellent
response was defined based on the latest American Thyroid Association Guidelines.
Univariate and multivariate analyses were performed for early Tg, delayed Tg, and
other clinical variables. RESULTS: In the multivariate analysis, tumor size [odds
ratio (OR) 1.716; 95% confidence interval (CI) 1.019-2.882; p = 0.042] and early
Tg level (OR 2.012; 95% CI 1.384-2.925, p < 0.001) independently predicted
excellent responses. The cutoff for the best early Tg level to predict a non
excellent response was 2.0 ng/mL. Delayed Tg was not a significant predictor (OR
0.992; 95% CI 0.969-1.015; p = 0.492). CONCLUSIONS: Early stimulated Tg
significantly predicted therapeutic response after rhTSH-aided RIT in patients
with DTC. Therefore, serum Tg should be measured before RIT to predict
therapeutic responses.
PMID- 28688089
TI - Predictive cartography of metal binders using generative topographic mapping.
AB - Generative topographic mapping (GTM) approach is used to visualize the chemical
space of organic molecules (L) with respect to binding a wide range of 41
different metal cations (M) and also to build predictive models for stability
constants (logK) of 1:1 (M:L) complexes using "density maps," "activity
landscapes," and "selectivity landscapes" techniques. A two-dimensional map
describing the entire set of 2962 metal binders reveals the selectivity and
promiscuity zones with respect to individual metals or groups of metals with
similar chemical properties (lanthanides, transition metals, etc). The GTM-based
global (for entire set) and local (for selected subsets) models demonstrate a
good predictive performance in the cross-validation procedure. It is also shown
that the data likelihood could be used as a definition of the applicability
domain of GTM-based models. Thus, the GTM approach represents an efficient tool
for the predictive cartography of metal binders, which can both visualize their
chemical space and predict the affinity profile of metals for new ligands.
PMID- 28688091
TI - Erratum to: clinical comparison of the effectiveness of 7- and 14-day intracanal
medications in root canal disinfection and inflammatory cytokines.
PMID- 28688090
TI - Application of a simple quantum chemical approach to ligand fragment scoring for
Trypanosoma brucei pteridine reductase 1 inhibition.
AB - There is a need for improved and generally applicable scoring functions for
fragment-based approaches to ligand design. Here, we evaluate the performance of
a computationally efficient model for inhibitory activity estimation, which is
composed only of multipole electrostatic energy and dispersion energy terms that
approximate long-range ab initio quantum mechanical interaction energies. We find
that computed energies correlate well with inhibitory activity for a compound
series with varying substituents targeting two subpockets of the binding site of
Trypanosoma brucei pteridine reductase 1. For one subpocket, we find that the
model is more predictive for inhibitory activity than the ab initio interaction
energy calculated at the MP2 level. Furthermore, the model is found to outperform
a commonly used empirical scoring method. Finally, we show that the results for
the two subpockets can be combined, which suggests that this simple nonempirical
scoring function could be applied in fragment-based drug design.
PMID- 28688092
TI - Mechanical loading increases pro-inflammatory effects of nitrogen-containing
bisphosphonate in human periodontal fibroblasts.
AB - OBJECTIVES: There is increasing evidence that inflammation and biomechanical
loading can influence the effects of bisphosphonates (BP). The aim of this study
was to investigate the influence of tensile strain application combined with IL
1beta and clodronate or zoledronate on human periodontal ligament fibroblasts
(HPdLF) in vitro. MATERIALS AND METHODS: HPdLF were cultured with 10 nM IL-1beta
and 5 MUM clodronate or zoledronate for 48 h. Cells were applied to cyclic
tensile strain (CTS; 3% elongation) for 12 h in vitro. Cell number was analyzed
directly after CTS by MTT assay. Gene expression of receptor activator of
cyclooxygenase-2 (COX-2) was investigated using real-time PCR. MMP-8, TIMP-1, and
PGE2 were measured by ELISA. Statistics were performed with SPSS (ANOVA, p <
0.05). RESULTS: Zoledronate reduced the cell number of HPdLF (60.3 vs. 100%),
which was significant when combined with IL-1beta. Combined with 3% CTS, this
effect was voided and cell number increased over the level of the control cells.
IL-1beta led to a 10-fold increase of COX-2 gene expression. Combined with CTS
and zoledronate, this increase was enhanced to a gene expression 70-fold that of
control cells with related PGE2 synthesis. Clodronate neither reduce the cell
number nor enhanced the COX-2 gene expression. CTS increased MMP-8 protein
synthesis. Combined with BP, this increase was voided. TIMP-1 protein synthesis
was increased at all conditions under CTS. CONCLUSIONS: Mechanical loading might
activate cell metabolism and abolish BP- and inflammation-induced reduction of
viability. Combination of mechanical loading, inflammation, and nitrogen
containing bisphosphonates can cause pro-inflammatory effects. CLINICAL
RELEVANCE: Periodontal inflammation should be treated initially before BP intake
to prevent decreased cell viability of the periodontium and increased
inflammation, which might be enhanced by the addition of mastication forces.
PMID- 28688093
TI - Influence of bisphosphonates on the adherence and metabolism of epithelial cells
and gingival fibroblasts to titanium surfaces.
AB - OBJECTIVES: To evaluate the effects of sodium alendronate (SA) and zoledronic
acid (ZA), on the adhesion and metabolism of epithelial cells and gingival
fibroblasts to titanium surfaces considering cell functions related to an
effective mucosal barrier around the implant. MATERIALS AND METHODS: Cells were
seeded onto titanium discs and incubated for 24 h. Then, serum-free DMEM
containing selected bisphosphonates (0, 0.5, 1, or 5 MUM) was added for 24 and 48
h. Factors related to the achievement of an effective mechanical and
immunological barrier-cell adhesion, viability, collagen epidermal growth factor,
and immunoglobulin synthesis-were evaluated. Data were analyzed by Kruskal-Wallis
and Mann-Whitney tests as well as by ANOVA and Tukey's tests, (alpha = 0.05).
RESULTS: The presence of bisphosphonates culminated in lower cell adhesion to the
titanium discs, particularly for SA at 5 MUM (40%) and ZA at all concentrations
(from 30 to 50%, according to increased concentrations). Reduced cell viability
occurred after exposing these cells to ZA (40%); however, only 5 MUM SA-treated
cells had decreased viability (30%). Reduced synthesis of growth factors and
collagen was observed when cells were reated with ZA (20 and 40%, respectively),
while about 70% of IgG synthesis was enhanced. CONCLUSION: Bisphosphonates
negatively affected the adhesion and metabolism of oral mucosal cells, and this
effect was related to the type of bisphosphonate as well as to concentration and
period of treatment. CLINICAL RELEVANCE: The negative effects of bisphosphonates
on oral mucosal cells can hamper the formation of an effective biological seal in
osseointegrated implants.
PMID- 28688094
TI - Risk Compensation Following Medical Male Circumcision: Results from a 1-Year
Prospective Cohort Study of Young School-Going Men in KwaZulu-Natal, South
Africa.
AB - PURPOSE: This study sought to assess risk compensation following voluntary
medical male circumcision of young school-going men. Risk compensation is defined
as an inadvertent increase in sexual risk behaviors and a corresponding decrease
in self-perceived risk for contracting HIV following the application of a risk
reduction technology. METHODS: This study documented the sexual practices of
circumcised (n = 485) and uncircumcised (n = 496) young men in 42 secondary
schools at three time points (baseline and 6 and 12 months) in a sub-district of
KwaZulu-Natal, South Africa. Study participants were aged from 16 to 24 years
old. RESULTS: At the end of the study period, there was no significant difference
between the two cohorts concerning learners' perceptions of being at risk of
contracting HIV (interaction effect: b = -0.12, p = 0.40). There was also no
significant difference in the number of sexual partners in the previous month
(interaction effect: b = -0.23, p = 0.15). The proportion of learners who have
never used a condom decreased significantly over time (time effect: b = -0.27, p
= 0.01), and there was no difference between the circumcised and uncircumcised
learners (interaction effect: b = -0.09, p = 0.91). CONCLUSIONS: Risk
compensation, as evidenced in this study over a 1-year period, was not associated
with undergoing voluntary medical male circumcision (VMMC) in our sample of young
school-going men. However, it is of concern that at the end of this study, less
than half of the sexually active sample in a high-HIV-prevalence community used
condoms consistently in the previous month (39% for both study cohorts). The
latter underscores the need to view VMMC as a potential entry point for planned
HIV and sexuality education interventions targeting young men in this community.
PMID- 28688096
TI - What or when? The impact of anticipated social action effects is driven by action
effect compatibility, not delay.
AB - Motor actions are facilitated if they are foreseeably being imitated rather than
counterimitated by social partners. Such beneficial effects of anticipated
imitation have been explained in terms of compatibility between one's own actions
and their anticipated consequences. Previous demonstrations of these effects
might alternatively be explained by consistently faster partner responses for
imitative than for nonimitative actions, however. This study contrasts both
explanations by using virtual coactors to disentangle the contributions of
anticipated action-effect compatibility and anticipated action-effect delay. The
data of two experiments support previous theoretical assumptions by showing that
the effects of anticipated imitation are indeed driven by compatibility rather
than delay.
PMID- 28688095
TI - The Relation of Light-to-Moderate Alcohol Consumption to Glucose Metabolism and
Insulin Resistance in Nondiabetic Adults: the Moderating Effects of Depressive
Symptom Severity, Adiposity, and Sex.
AB - PURPOSE: We examined the relation of alcohol consumption to glucose metabolism
and insulin resistance (IR) as a function of depressive symptoms, adiposity, and
sex. METHOD: Healthy adults (aged 18-65 years) provided fasting blood samples and
information on lifestyle factors. Alcohol intake was categorized as never,
infrequent (1-3 drinks/month), occasional (1-7 drinks/week), and regular (>=2
drinks/day) drinkers. The Beck Depression Inventory (BDI) was used to assess
symptom severity. Primary outcomes were fasting insulin, glucose, and IR assessed
by the homeostasis model assessment (HOMA). RESULTS: In univariate analysis,
alcohol consumption was negatively associated with HOMA-IR (p = 0.03), insulin (p
= 0.007), and body mass index (BMI) (p = 0.04), but not with glucose or BDI.
Adjusting for potential confounders including BMI, alcohol consumption was
associated with HOMA-IR (p = 0.01) and insulin (p = 0.009) as a function of BDI
and sex. For women with minimal depressive symptoms, light-to-moderate alcohol
consumption was associated with lower HOMA-IR and insulin. Alcohol consumption
was not associated with metabolic markers in women with higher depressive
symptoms and in men. In analysis using BMI as a continuous moderator, alcohol
consumption was only associated with insulin (p = 0.004). Post-hoc comparisons
between BMI groups (<25 vs >=25 kg/m2) revealed that light-to-moderate alcohol
consumption was associated with lower insulin but only in subjects with BMI >= 25
kg/m2. CONCLUSIONS: The benefits of light-to-moderate alcohol consumption on
fasting insulin and IR are sex dimorphic and appear to be independently moderated
by adiposity and depressive symptom severity.
PMID- 28688097
TI - B Lymphocyte Chemoattractant (CXCL13) Is an Indicator of Acute Gastrointestinal
GVHD in Murine Model.
AB - Gastrointestinal acute graft-vs.-host disease (GI aGVHD) remains a significant
obstacle to the success of allogeneic hematopoietic cell transplantation and is a
major cause of morbidity and mortality. In addition, GI aGVHD is often clinically
indistinguishable from other causes of GI dysfunction such as conditioning
regimen toxicity, infections, or medications, which complicates the diagnosis.
Thus, specific biomarkers are needed to help improve diagnosis and obtain a
deeper understanding of the cytokine changes in GI aGVHD. An MHC-mismatched model
of aGVHD was established by transplanting 1 * 107 bone marrow nuclear cells and 3
* 107 spleen cells from C57/Bl6 mice or from BALB/c mice into lethally irradiated
BALB/c recipients. The mice in the allogeneic transplantation group were
intraperitoneally treated with 20 mg kg-1 day-1 cyclosporin A after aGVHD
developed. Five micrograms of lipopolysaccharide were administered
intraperitoneally daily to syngeneic recipients at day 11 to imitate infection;
the same volume of phosphate-buffered saline was administered to control mice.
The mice were killed at the indicated time points. Forty molecules derived from
the GI tract were screened cytokine array. The data demonstrated that the
expression of B lymphocyte chemoattractant (CXCL13) was increased by ~10-, 12-,
and 16-fold upon the occurrence of aGVHD compared with infection, aGVHD after
treatment, and the syngeneic control group, respectively. Thus, the elevation of
BLC (CXCL13) is an indicator of acute GI GVHD.
PMID- 28688098
TI - The Attenuation of 14-3-3zeta is Involved in the Caffeic Acid-Blocked
Lipopolysaccharide-Stimulated Inflammatory Response in RAW264.7 Macrophages.
AB - Inflammation plays important roles in the initiation and progress of many
diseases. Caffeic acid (CaA) is a naturally occurring hydroxycinnamic acid
derivative, which shows hypotoxicity and diverse biological functions, including
anti-inflammation. The molecular mechanisms involved in the CaA-inhibited
inflammatory response are very complex; generally, the down-regulated
phosphorylation of such important transcriptional factors, for example, nuclear
factor kappaB (NF-kappaB) and signal transducers and activators of transcription
3 (STAT-3), plays an important role. Here, we found that in RAW264.7 macrophage
cells, CaA blocked lipopolysaccharide (LPS)-stimulated inflammatory response by
attenuating the expression of 14-3-3zeta (a phosphorylated protein regulator).
Briefly, the increased expression of 14-3-3zeta was involved in the LPS-induced
inflammatory response. CaA blocked the LPS-elevated 14-3-3zeta via attenuating
the LPS-induced tumor necrosis factor-alpha (TNF-alpha) secretion and via
enhancing the 14-3-3zeta ubiquitination. These processes inhibited the LPS
induced activation (phosphorylation) of NF-kappaB and STAT-3, in turn blocked the
transcriptional activation of inducible NO synthase (iNOS), interleukin-6 (IL-6),
and TNF-alpha, and finally attenuated the productions of nitric oxide (NO), IL-6,
and TNF-alpha. By understanding a novel mechanism whereby CaA inhibited the 14-3
3zeta, our study expanded the understanding of the molecular mechanisms involved
in the anti-inflammation potential induced by CaA.
PMID- 28688099
TI - Increased O-Linked N-Acetylglucosamine Modification of NF-KappaB and Augmented
Cytokine Production in the Placentas from Hyperglycemic Rats.
AB - Inflammation as a result of NF-kappaB activation may result from the classical
(canonical) pathway, with disconnection of the IkappaB inhibitor and subsequent
nuclear translocation or, alternatively, by post-translational modifications of
modulatory proteins or NF-kappaB subunits (non-canonical pathway). We
hypothesized that hyperglycemia-induced increased glycosylation with O-linked N
acetylglucosamine (O-GlcNAc) of NF-kappaB in placental tissue leads to augmented
production of pro-inflammatory cytokines, culminating in placental dysfunction
and fetal restriction growth. Single injections of streptozotocin (40 mg/kg) or
vehicle were used to induce hyperglycemia or normoglycemia, respectively, in
female Wistar rats. After 3 days, rats were mated and pregnancy confirmed.
Placental tissue was collected at 21 days of pregnancy. Placental expression of
p65 subunit was similar between groups. However, nuclear translocation of p65
subunit, showing greater activation of NF-kappaB, was increased in the
hyperglycemic group. Reduced expression of IkappaB and increased expression of
phosphorylated IkappaBSer32 were observed in the placenta from hyperglycemic
rats, demonstrating increased classical NF-kappaB activation. Augmented
modification of O-GlcNAc-modified proteins was found in the placenta from
hyperglycemic rats and p65 subunit was a key O-GlcNAc target, as demonstrated by
immunoprecipitation. Tumor necrosis factor-alpha (TNF-alpha) and interleukin-6
(IL-6) expressions were increased in the placenta from hyperglycemic rats.
Furthermore, placental weight was increased, whereas fetal weight was decreased
under hyperglycemic conditions. TNF-alpha and IL-6 demonstrated positive
correlations with placental weight and negative correlations with fetal weight
and placental efficiency. Therefore, under hyperglycemic conditions, a modulatory
role of O-GlcNAc in NF-kappaB activity was demonstrated in the placenta,
contributing to fetal and placental dysfunction due to inflammatory cytokine
exacerbation.
PMID- 28688100
TI - Reply to Letter to the Editor "Staple Line Reinforcement in Laparoscopic Sleeve
Gastrectomy: Experience in 1023 Consecutive Cases" Obesity Surgery June 2017
Issue 6: 1474-80 by Sepulveda et al.
PMID- 28688101
TI - Response to: Staple Line Reinforcement in Laparoscopic Sleeve Gastrectomy:
Experience in 1023 Consecutive Cases Obesity Surgery June 2017 Issue 6: 1474-80.
PMID- 28688102
TI - How to Switch to the Switch: Implementation of Biliopancreatic Diversion with
Duodenal Switch into Practice.
AB - The biliopancreatic diversion with duodenal switch (BPD/DS), a modification of
the classic Scopinaro procedure, carries the highest rate of success in terms of
weight loss, comorbid resolution, and maintenance of weight loss. The substantial
challenges, technical complexity, and expected roadblocks of adding BPD/DS option
to the bariatric surgeon's resources are reflected in the number of BPD/DS
procedure performed in the USA, being less than 1% of all bariatric surgeries.
Adjustments to the length of the common channel and the size of the vertical
sleeve would increase the pool of candidates for BPD/DS and offer comprehensive
management of obesity and metabolic comorbidities. Proper educational programs
and multiple proctoring to bariatric surgeons aid to implement BPD/DS to their
practice.
PMID- 28688104
TI - Erratum to: Building practitioner networks to support dissemination and
implementation of evidence-based programs in community settings.
PMID- 28688103
TI - Treatment of Common Bile Duct Stones in Gastric Bypass Patients with Laparoscopic
Transgastric Endoscopic Retrograde Cholangiopancreatography.
PMID- 28688105
TI - Intussusception in celiac disease: Is it a common feature in children?
AB - BACKGROUND AND AIM: There are sporadic reports of occurrence of intussusception
in celiac disease (CD) but no systematic study yet. We prospectively studied the
prevalence and natural history of intussusception in newly diagnosed CD. METHODS:
From January 2010 to October 2013, 150 children, diagnosed to have CD on the
basis of positive serology and duodenal biopsy, were recruited in this study.
Abdominal ultrasonography was carried out before starting gluten-free diet (GFD)
and repeated in those who had intussusception, on day 3 and then weekly till the
resolution of intussusception. RESULTS: The median age was 72 (range, 16-204)
months, and 79 (53%) were boys. Diarrhea was the presenting symptom in 119 (79%)
cases. A total of 45 intussusceptions were detected in 37 (25%) children. Out of
45 intussusceptions, 95% involved small bowel. All but one had asymptomatic
intussusception. On GFD, intussusception resolved spontaneously within 7 days in
65%, within 14 days in 84%, and within 28 days in 92% of cases, and none required
surgical or hydrostatic reduction. On univariate analysis, younger age, low
weight z score, presentation with diarrhea, abdominal distension, rickets, lower
serum albumin, more severe villous atrophy, and refeeding syndrome were more
common in children with intussusception. On multivariate analysis, abdominal
distension and hypoalbuminemia were found to be significantly associated with
intussusception. CONCLUSIONS: Intussusception is frequently (25%) seen in
children with newly diagnosed CD, generally asymptomatic and resolves
spontaneously on GFD. It is often associated with more severe disease. Children
with CD and intussusception should not be subjected to surgical/radiological
intervention.
PMID- 28688106
TI - Human milk exosomes and their microRNAs survive digestion in vitro and are taken
up by human intestinal cells.
AB - SCOPE: Human milk exosomes provide a natural means of genetic material transfer
to infants; however, the effect of gastric/pancreatic digestion milk exosomes
stability and their microRNA content is largely unknown. METHODS AND RESULTS: We
took a simulated gastric/pancreatic digestion protocol to perform in vitro
digestion of milk exosomes, explore intestinal epithelial uptake, and further
elucidate microRNA responses to digestion at early-, mid-, late lactation by
massive parallel sequencing. Both undigested and digested exosomes enter human
intestinal crypt-like cells (HIEC), with evidence of nuclear localization. We
identified 288 mature microRNAs from all 24 exosome samples, and an additional
610 at low abundance. A large number of synapse development- and immune-related
microRNAs were identified. hsa-miR-22-3p was the most abundant microRNA, and the
top 15 microRNAs contributed ~11% of the sequencing reads. Upon digestion, the
overall microRNA abundance in human milk exosomes was stable. CONCLUSION: Our
results for the first time reveal the survivability and complexity of human milk
exosome microRNAs upon simulated gastric/pancreatic digestion, and the dynamics
during lactation stages. The results suggest a previously underexplored area of
infant response to genetic material in human milk exosomes.
PMID- 28688107
TI - Evaluating amber force fields using computed NMR chemical shifts.
AB - NMR chemical shifts can be computed from molecular dynamics (MD) simulations
using a template matching approach and a library of conformers containing
chemical shifts generated from ab initio quantum calculations. This approach has
potential utility for evaluating the force fields that underlie these
simulations. Imperfections in force fields generate flawed atomic coordinates.
Chemical shifts obtained from flawed coordinates have errors that can be traced
back to these imperfections. We use this approach to evaluate a series of AMBER
force fields that have been refined over the course of two decades (ff94, ff96,
ff99SB, ff14SB, ff14ipq, and ff15ipq). For each force field a series of MD
simulations are carried out for eight model proteins. The calculated chemical
shifts for the 1 H, 15 N, and 13 Ca atoms are compared with experimental values.
Initial evaluations are based on root mean squared (RMS) errors at the protein
level. These results are further refined based on secondary structure and the
types of atoms involved in nonbonded interactions. The best chemical shift for
identifying force field differences is the shift associated with peptide protons.
Examination of the model proteins on a residue by residue basis reveals that
force field performance is highly dependent on residue position. Examination of
the time course of nonbonded interactions at these sites provides explanations
for chemical shift differences at the atomic coordinate level. Results show that
the newer ff14ipq and ff15ipq force fields developed with the implicitly
polarized charge method perform better than the older force fields.
PMID- 28688109
TI - Root causes and social consequences of birth injuries in Western Uganda.
PMID- 28688108
TI - A physiologically based pharmacokinetic modelling approach to predict
buprenorphine pharmacokinetics following intravenous and sublingual
administration.
AB - AIMS: Opioid dependence is associated with high morbidity and mortality.
Buprenorphine (BUP) is approved by the Food and Drug Administration to treat
opioid dependence. There is a lack of clear consensus on the appropriate dosing
of BUP due to interpatient physiological differences in absorption/disposition,
subjective response assessment and other patient comorbidities. The objective of
the present study was to build and validate robust physiologically based
pharmacokinetic (PBPK) models for intravenous (IV) and sublingual (SL) BUP as a
first step to optimizing BUP pharmacotherapy. METHODS: BUP-PBPK modelling and
simulations were performed using SimCyp(r) by incorporating the physiochemical
properties of BUP, establishing intersystem extrapolation factors-based in vitro
in-vivo extrapolation (IVIVE) methods to extrapolate in vitro enzyme activity
data, and using tissue-specific plasma partition coefficient estimations.
Published data on IV and SL-BUP in opioid-dependent and non-opioid-dependent
patients were used to build the models. Fourteen model-naive BUP-PK datasets were
used for inter- and intrastudy validations. RESULTS: The IV and SL-BUP-PBPK
models developed were robust in predicting the multicompartment disposition of
BUP over a dosing range of 0.3-32 mg. Predicted plasma concentration-time
profiles in virtual patients were consistent with reported data across five
single-dose IV, five single-dose SL and four multiple dose SL studies. All PK
parameter predictions were within 75-137% of the corresponding observed data. The
model developed predicted the brain exposure of BUP to be about four times higher
than that of BUP in plasma. CONCLUSION: The validated PBPK models will be used in
future studies to predict BUP plasma and brain concentrations based on the
varying demographic, physiological and pathological characteristics of patients.
PMID- 28688110
TI - Rapid determination of lipophilic vitamins in human serum by ultra-high
performance liquid chromatography using a fluorinated column and high-throughput
miniaturized liquid-liquid extraction.
AB - A high-throughput miniaturized liquid-liquid extraction procedure followed by a
simple ultra-high performance liquid chromatography method coupled with
fluorescence detection for bioanalytical analysis of all tocopherol isomers and
retinol in human serum has been developed and validated. In the extraction
procedure, a synthetic internal standard tocol was used, which does not occur in
the human body. The separation of structurally related vitamins was achieved
using a new generation of pentafluorophenyl propyl core-shell stationary phase
with elution using methanol and an aqueous solution of ammonium acetate. The
fluorescence of retinol and tocopherol isomers was detected at lambdaex = 325,
295 nm and lambdaem = 480, 325 nm, respectively. The rapid baseline separation
of all analytes was accomplished within 4.0 min. The sensitivity of method was
demonstrated with lower limits of quantification: retinol 0.01 MUM, alpha
tocopherol 0.38 MUM, beta-tocopherol 0.18 MUM, gamma-tocopherol 0.14 MUM, and
delta-tocopherol 0.01 MUM. Possible application of this method in clinical
practice was confirmed by the analysis of human serum samples from healthy
volunteers. Finally, the simultaneous determination of retinol and all tocopherol
isomers in human serum can enable the clarification of their role in metabolism
and in diseases such as cancer.
PMID- 28688111
TI - Vasopressin and metabolic disorders: translation from experimental models to
clinical use.
AB - Vasopressin has many physiological actions in addition to its well-defined role
in the control of fluid homeostasis and urine concentration. An increasing body
of evidence suggests that the vasopressin-hydration axis plays a role in glucose
homeostasis. This review summarizes the knowledge accumulated over the last
decades about the influence of vasopressin in the short-term regulation of
glycaemia. It describes the possible role of this hormone through activation of
V1a and V1b receptors on liver and pancreas functions and on the hypothalamic
pituitary-adrenal axis. Moreover, we report recent in vivo studies demonstrating
the role of vasopressin in the long-term regulation of glycaemia. Indeed, V1a- or
double-V1aV1b-receptor knockout mice display significant changes in the glucose
and lipid metabolism. In rats, sustained high V1aR activation increases basal
glycaemia and aggravates glucose intolerance in obese rats. Finally, the
translation from animal findings to human was evidenced by epidemiological and
genetic studies that showed that high vasopressin level is a risk factor for
hyperglycaemia, metabolic disorders and diabetes.
PMID- 28688113
TI - Assessing clinical probability of pulmonary embolism: prospective validation of
the simplified Geneva score.
AB - : Essentials The simplified Geneva score allows easier pretest probability
assessment of pulmonary embolism (PE). We prospectively validated this score in
the ADJUST-PE management outcome study. The study shows that it is safe to manage
patients with suspected PE according to this score. The simplified Geneva score
is now ready for use in routine clinical practice. SUMMARY: Background Pretest
probability assessment by a clinical prediction rule (CPR) is an important step
in the management of patients with suspected pulmonary embolism (PE). A
limitation to the use of CPRs is that their constitutive variables and
corresponding number of points are difficult to memorize. A simplified version of
the Geneva score (i.e. attributing one point to each variable) has been proposed
but never been prospectively validated. Aims Prospective validation of the
simplified Geneva score (SGS) and comparison with the previous version of the
Geneva score (GS). Methods In the ADJUST-PE study, which had the primary aim of
validating the age-adjusted D-dimer cut-off, the SGS was prospectively used to
determine the pretest probability in a subsample of 1621 study patients. Results
Overall, PE was confirmed in 294 (18.1%) patients. Using the SGS, 608 (37.5%),
980 (60.5%) and 33 (2%) were classified as having a low, intermediate and high
clinical probability. Corresponding prevalences of PE were 9.7%, 22.4% and 45.5%;
490 (30.1%) patients with low or intermediate probability had a D-dimer level
below 500 MUg L-1 and 653 (41.1%) had a negative D-dimer test according to the
age-adjusted cut-off. Using the GS, the figures were 491(30.9%) and 650 (40.9%).
None of the patients considered as not having PE based on a low or intermediate
SGS and negative D-dimer had a recurrent thromboembolic event during the 3-month
follow-up. Conclusions The use of SGS has similar efficiency and safety to the GS
in excluding PE in association with the D-dimer test.
PMID- 28688114
TI - Shape analysis of the jaws between two minnow species over ontogeny.
AB - This study compares sand shiner (Notropis stramineus) and silverjaw (Ericymba
buccata) minnows, in terms of the morphological shape changes of the upper,
lower, and pharyngeal jaws over ontogeny. These two species of minnows initially
feed on midge larvae and undergo an ontogenic prey shift. The traditional
morphometrics measured-total length, snout-to-vent length, eye diameter,
premaxilla length, lower jaw length, gape-were regressed onto total length to
test for allometry. Digital pictures were processed with tpsDig and further
analyzed with MorphoJ utilizing a regular geometric morphometrics procedure using
principle component analyses. We examined gut contents for 16 fish of each
species. For the silverjaw minnows, we found all jaw variables to exhibit
positive allometric growth with increasing total length, while most of the jaw
variables for the sand shiner exhibited negative allometric growth with
increasing total length. This correlates with an ontogenic prey shift for both
species. Sand shiner minnows have been found to be more omnivorous, feeding on
algae later in life, while silverjaw minnows undergo a prey shift to larger
invertebrates. These species lack oral dentition causing an increased reliance on
the pharyngeal apparatus. Principle component analyses revealed elongation of
pharyngeal jaw elements in the silverjaw minnows and a relative shortening and
bulking of pharyngeal jaws in the sand shiner minnows. The ontogenic dietary
shifts observed in these two species provide possible explanation for the
morphological changes over ontogeny in jaw elements, which are likely enabling
these species to occupy the same habitat with little niche overlap.
PMID- 28688115
TI - A Monte Carlo study of the effect of an ultrasound transducer on surface dose
during intrafraction motion imaging for external beam radiation therapy.
AB - PURPOSE: The aim of this study was to estimate changes in surface dose due to the
presence of the Clarity AutoscanTM ultrasound (US) probe during prostate
radiotherapy using Monte Carlo (MC) methods. METHODS: MC models of the Autoscan
US probe were developed using the BEAMnrc/DOSXYZnrc code based on kV and MV CT
images. CT datasets were converted to voxelized mass density phantoms using a CT
number-to-mass density calibration. The dosimetric effect of the probe, in the
contact region (an 8 mm * 12 mm single layer of voxels), was investigated using a
phantom set-up mimicking two scenarios (a) a transperineal imaging configuration
(radiation beam perpendicular to the central US axial direction), and (b) a
transabdominal imaging configuration (radiation beam parallel to the central US
axial direction). For scenario (a), the dosimetric effect was evaluated as a
function of the probe to inferior radiation field edge distance. Clinically
applicable distances from 5 mm separation to 2 mm overlap were determined from
the radiotherapy plans of 27 patients receiving Clarity imaging. Overlaps of 3 to
14 (1 to 3 SD) mm were also considered to include the effect of interfraction
motion correction. The influence of voxel size on surface dose estimation was
investigated. Approved clinical plans from two prostate patients were used to
simulate worst-case dosimetric impact of the probe when large couch translations
were applied to correct for interfraction prostate motion. RESULTS: The
dosimetric impact of both the MV and kV probe models agreed within +/-2% for both
beam configurations. For scenario (a) and 1 mm voxel model, the probe gave mean
dose increases of 1.2% to 4.6% (of the dose at isocenter) for 5 mm separation to
0 mm overlap in the probe-phantom contact region, respectively. This increased to
27.5% for the largest interfraction motion correction considered (14 mm overlap).
For separations of >= 2 mm dose differences were < 2%. Simulated dose
perturbations were found to be superficial; for the 14 mm overlap the dose
increase reduced to < 3% at 5.0 mm within the phantom. For scenario (b), dose
increases due to the probe were < 5% in all cases. The dose increase was
underestimated by up to ~13% when the voxel size was increased from 1 mm to 3 mm.
MC simulated dose to the PTV and OARs for the two clinical plans considered
showed good agreement with commercial treatment planning system results (within
2%). Mean dose increases due to the presence of the probe, after the maximum
interfraction motion correction, were ~16.3% and ~8.0%, in the contact region,
for plan 1 and plan 2, respectively. CONCLUSIONS: The presence of the probe
results in superficial dose perturbations for patients with an overlap between
the probe and the radiation field present in either the original treatment plan
or due to translation of the radiation field to simulate correction of
interfraction internal prostate motion.
PMID- 28688112
TI - Consumption of fruits, vegetables and fruit juices and differentiated thyroid
carcinoma risk in the European Prospective Investigation into Cancer and
Nutrition (EPIC) study.
AB - Fruit and vegetable (F&V) intake is considered as probably protective against
overall cancer risk, but results in previous studies are not consistent for
thyroid cancer (TC). The purpose of this study is to examine the association
between the consumption of fruits, vegetables, fruit juices and differentiated
thyroid cancer risk within the European Prospective Investigation into Cancer and
Nutrition (EPIC) study. The EPIC study is a cohort including over half a million
participants, recruited between 1991 and 2000. During a mean follow-up of 14
years, 748 incident first primary differentiated TC cases were identified. F&V
and fruit juice intakes were assessed through validated country-specific dietary
questionnaires. Hazard ratios (HRs) and 95% confidence intervals (CIs) were
estimated using Cox regression models adjusted for potential confounding factors.
Comparing the highest versus lowest quartile of intake, differentiated TC risk
was not associated with intakes of total F&V (HR: 0.89; 95% CI: 0.68-1.15; p
trend = 0.44), vegetables (HR: 0.89; 95% CI: 0.69-1.14; p-trend = 0.56), or fruit
(HR: 1.00; 95% CI: 0.79-1.26; p-trend = 0.64). No significant association was
observed with any individual type of vegetable or fruit. However, there was a
positive borderline trend with fruit juice intake (HR: 1.23; 95% CI: 0.98-1.53; p
trend = 0.06). This study did not find any significant association between F&V
intakes and differentiated TC risk; however a positive trend with fruit juice
intake was observed, possibly related to its high sugar content.
PMID- 28688116
TI - Towards Catalytic Ammonia Oxidation to Dinitrogen: A Synthetic Cycle by Using a
Simple Manganese Complex.
AB - Oxidation of the nucleophilic nitride, (salen)Mn=N (1) with stoichiometric [Ar3
N][X] initiated a nitride coupling reaction to N2 , a major step toward catalytic
ammonia oxidation (salen=N,N'-bis(salicylidene)-ethylenediamine dianion; Ar=p
bromophenyl; X=[SbCl6 ]- or [B(C6 F5 )4 ]- ). N2 production was confirmed by mass
spectral analysis of the isotopomer, 1-15 N, and the gas quantified. The metal
products of oxidation were the reduced MnIII dimers, [(salen)MnCl]2 (2) or
[(salen)Mn(OEt2 )]2 [B(C6 F5 )4 ]2 (3) for X=[SbCl6 ]- or [B(C6 F5 )4 ]- ,
respectively. The mechanism of nitride coupling was probed to distinguish a
nitridyl from a nucleophilic/electrophilic coupling sequence. During these
studies, a rare mixed-valent MnV /MnIII bridging nitride, [(salen)MnV (MU-N)MnIII
(salen)][B(C6 F5 )4 ] (4), was isolated, and its oxidation-state assignment was
confirmed by X-ray diffraction (XRD) studies, perpendicular and parallel-mode EPR
and UV/Vis/NIR spectroscopies, as well as superconducting quantum interference
device (SQUID) magnetometry. We found that 4 could subsequently be oxidized to 3.
Furthermore, in view of generating a catalytic system, 2 can be re-oxidized to 1
in the presence of NH3 and NaOCl closing a pseudo-catalytic "synthetic" cycle.
Together, the reduction of 1->2 followed by oxidation of 2->1 yield a genuine
synthetic cycle for NH3 oxidation, paving the way to the development of a fully
catalytic system by using abundant metal catalysis.
PMID- 28688117
TI - Serologic evidence of West Nile virus and Usutu virus infections in Eurasian
coots in the Netherlands.
AB - West Nile virus (WNV) and Usutu virus (USUV) are arboviruses that are maintained
in enzootic transmission cycles between mosquitoes and birds and are occasionally
transmitted to mammals. As arboviruses are currently expanding their geographic
range and emerging in often unpredictable locations, surveillance is considered
an important element of preparedness. To determine whether sera collected from
resident and migratory birds in the Netherlands as part of avian influenza
surveillance would also represent an effective source for proactive arbovirus
surveillance, a random selection of such sera was screened for WNV antibodies
using a commercial ELISA. In addition, sera of jackdaws and carrion crows
captured for previous experimental infection studies were added to the selection.
Of the 265 screened serum samples, 27 were found to be WNV-antibody-positive, and
subsequent cross-neutralization experiments using WNV and USUV confirmed that
five serum samples were positive for only WNV-neutralizing antibodies and seven
for only USUV. The positive birds consisted of four Eurasian coots (Fulica atra)
and one carrion crow (Corvus corone) for WNV, of which the latter may suggest
local presence of the virus, and only Eurasian coots for USUV. As a result, the
screening of a small selection of serum samples originally collected for avian
influenza surveillance demonstrated a seroprevalence of 1.6% for WNV and 2.8% for
USUV, suggesting that this sustained infrastructure could serve as a useful
source for future surveillance of arboviruses such as WNV and USUV in the
Netherlands.
PMID- 28688119
TI - Catalytic Metallodrugs: Substrate-Selective Metal Catalysts as Therapeutics.
AB - Metal complexes that catalyze inactivation and degradation of biomolecular
targets can be developed into novel therapeutics (catalytic metallodrugs) against
a variety of diseases. Despite recent advances in the field, a lack of substrate
selectivity is a major hindrance to the development of catalytic metallodrugs for
application in clinical practice. Improved targeting can minimize nonselective
activity and the potential for side effects. Herein, we focus on recent
developments toward novel metal catalysts that exhibit substrate selectivity
against a variety of therapeutically relevant biomolecules. Design strategies for
developing selective catalytic metallodrugs are also highlighted.
PMID- 28688118
TI - A pair of DICER1-positive monozygotic twins: One with pleuropulmonary blastoma,
another with acute transient hepatitis.
AB - Pleuropulmonary blastoma (PPB) is the most common primary malignant neoplasm of
the lung in children that is associated with a germline mutation in DICER1. In
this report, we share an interesting case of a pair of monozygotic twins: one of
them developed PPB when she was 4-year old, while the other developed acute
transient hepatitis when she was 5-year old. Next-Gen sequencing for DICER1
mutations of their family revealed that both twins and their mother had c.C3675A
mutation. The mother also had a history of multinodular goiter. Identification of
DICER1 mutation carriers and close surveillance of individuals at risk for DICER1
syndrome may allow early detection and hence better outcome.
PMID- 28688120
TI - Electron beam water calorimetry measurements to obtain beam quality conversion
factors.
AB - PURPOSE: To provide results of water calorimetry and ion chamber measurements in
high-energy electron beams carried out at the National Research Council Canada
(NRC). There are three main aspects to this work: (a) investigation of the
behavior of ionization chambers in electron beams of different energies with
focus on long-term stability, (b) water calorimetry measurements to determine
absorbed dose to water in high-energy beams for direct calibration of ion
chambers, and (c) using measurements of chamber response relative to reference
ion chambers, determination of beam quality conversion factors, kQ , for several
ion chamber types. METHODS: Measurements are made in electron beams with energies
between 8 MeV and 22 MeV from the NRC Elekta Precise clinical linear accelerator.
Ion chamber measurements are made as a function of depth for cylindrical and
plane-parallel ion chambers over a period of five years to investigate the
stability of ion chamber response and for indirect calibration. Water calorimetry
measurements are made in 18 MeV and 22 MeV beams. An insulated enclosure with
fine temperature control is used to maintain a constant temperature (drifts less
than 0.1 mK/min) of the calorimeter phantom at 4 degrees C to minimize effects
from convection. Two vessels of different designs are used with calibrated
thermistor probes to measure radiation induced temperature rise. The vessels are
filled with high-purity water and saturated with H2 or N2 gas to minimize the
effect of radiochemical reactions on the measured temperature rise. A set of
secondary standard ion chambers are calibrated directly against the calorimeter.
Finally, several other ion chambers are calibrated in the NRC 60 Co reference
field and then cross-calibrated against the secondary standard chambers in
electron beams to realize kQ factors. RESULTS: The long-term stability of the
cylindrical ion chambers in electron beams is better (always <0.15%) than plane
parallel chambers (0.2% to 0.4%). Calorimetry measurements made at 22 MeV with
two different vessel geometries are consistent within 0.2% after correction for
the vessel perturbation. Measurements of absorbed dose calibration coefficients
for the same secondary standard chamber separated in time by 10 yr are within
0.2%. Drifts in linac output that would affect the transfer of the standard are
mitigated to the 0.1% level by performing daily ion chamber normalization
measurements. Calibration coefficients for secondary standard ion chambers can be
achieved with uncertainties less than 0.4% (k = 1) in high-energy electron beams.
The additional uncertainty in deriving calibration coefficients for well-behaved
chambers indirectly against the secondary standard reference chambers is
negligible. The kQ factors measured here differ by up to 1.3% compared to those
in TG-51, an important change for reference dosimetry measurements. CONCLUSIONS:
The measurements made here of kQ factors for eight plane-parallel and six
cylindrical ion chambers will impact future updates of reference dosimetry
protocols by providing some of the highest quality measurements of this crucial
dosimetric parameter.
PMID- 28688121
TI - Assessing the cost of implementing the 2011 Society of Obstetricians and
Gynecologists of Canada and Canadian College of Medical Genetics practice
guidelines on the detection of fetal aneuploidies.
AB - BACKGROUND: The Society of Obstetricians and Gynecologists of Canada and the
Canadian College of Medical Genetics published guidelines, in 2011, recommending
replacement of karyotype with quantitative fluorescent polymerase chain reaction
when prenatal testing is performed because of an increased risk of a common
aneuploidy. STUDY OBJECTIVE: This study's objective is to perform a cost analysis
following the implementation of quantitative fluorescent polymerase chain
reaction as a stand-alone test. RESULTS: A total of 658 samples were received
between 1 April 2014 and 31 August 2015: 576 amniocentesis samples and 82
chorionic villi sampling. A chromosome abnormality was identified in 14% (93/658)
of the prenatal samples tested. The implementation of the 2011 Society of
Obstetricians and Gynecologists of Canada and the Canadian College of Medical
Genetics guidelines in Edmonton and Northern Alberta resulted in a cost savings
of $46 295.80. The replacement of karyotype with chromosomal microarray for some
indications would be associated with additional costs. CONCLUSION: The
implementation of new test methods may provide cost savings or added costs. Cost
analysis is important to consider during the implementation of new guidelines or
technologies. (c) 2017 John Wiley & Sons, Ltd.
PMID- 28688123
TI - Insular mammalian fauna dynamics and paleogeography: A lesson from the Western
Mediterranean islands.
AB - Since the time of Darwin (1859) and Wallace (1869), islands have been regarded by
scientists as a prime target for scrutinizing the forces that may influence
evolution and diversification and important elements in biogeographic studies.
This research aims to scrutinize whether and to what extent the composition and
structure of past mammal insular faunas and their changes through time may
provide sound clues for inferring the paleogeographical evolution of a region. As
a case study, I critically analyzed the dynamics shown by the Plio-Pleistocene
mammalian fauna of 3 Western Mediterranean insular districts, the Balearic
Islands, Sardinia and Sicily, each characterized by its own peculiar
paleobiogeographical evolutionary history. The revision of faunas and the
critical analysis of the dispersal ability of the ancestors of island settlers
have allowed hypothesizing on the time and mode of island colonization. The
results obtained confirm that the early isolation of the Balearic Islands from
the mainland led to the establishment of an endemic fauna since the pre-Messinian
Miocene (?Astaracian European Land Mammal Age, MN7/8), and that Sardinia has
definitely been isolated since the Pliocene, although dispersal events led to
some faunal turnovers during the Pleistocene. In addition, the results suggest
for Sicily a complex, still imperfectly disentangled history of alternate phases
of complete separation and sporadic, more or less difficult connections with
southern Italy.
PMID- 28688122
TI - Diminazene aceturate prevents nephropathy by increasing glomerular ACE2 and AT2
receptor expression in a rat model of type1 diabetes.
AB - BACKGROUND AND PURPOSE: One of the protective actions of angiotensin converting
enzyme-2 (ACE2) is the inactivation of angiotensin II. Expression and activity of
ACE2 was reduced in glomeruli of diabetic patients and in animal models of
diabetes. Recently the potential role of recombinant ACE2 administration in
preventing diabetic nephropathy (DN) has been shown. Here we have tested the
effects of the ACE2 activator, diminazene aceturate (DIZE), in a model of DN.
EXPERIMENTAL APPROACH: Male Wistar rats were rendered diabetic using a single
dose of streptozotocin (55 mg.kg-1 , i.p.). After 4 weeks, diabetic animals were
divided into experimental groups and treated with DIZE, at a low dose (5 mg.kg-1
.day-1 ), a high dose (15 mg.kg-1 .day-1 ) and the high dose with of the AT2
receptor antagonist PD123319 (10 mg.kg-1 .day-1 ). At the end of the treatment ,
kidneys from all the groups were collected and processed separately for
glomerular isolation, protein isolation, mRNA extraction and for
immunohistochemical studies. KEY RESULTS: Treatment with DIZE restored ACE2
expression in glomeruli and increased expression of AT2 receptors in whole kidney
and isolated glomeruli of diabetic animals. DIZE administration reduced
angiotensin II levels and increased angiotensin-(1-7) levels in diabetic kidney.
However, PD123319 treatment reversed all these actions of DIZE. CONCLUSIONS AND
IMPLICATIONS: DIZE treatment reduced diabetes-induced renal damage as shown by
reduction of fibrosis and apoptosis. These protective actions of DIZE were
blocked by the AT2 receptor antagonist. Taken together, these results suggest
that DIZE protected against DN through the ACE2/angiotensin-(1-7)/ AT2 receptor
axis.
PMID- 28688124
TI - Impact of the pretreatment Glasgow prognostic score on treatment tolerance,
toxicities, and survival in patients with advanced head and neck cancer
undergoing concurrent chemoradiotherapy.
AB - BACKGROUND: The purpose of this study was to evaluate the impact of the
pretreatment Glasgow prognostic score on treatment-related toxicities, tolerance,
and survival in patients with advanced head and neck cancers undergoing
concurrent chemoradiotherapy (CRT). METHODS: We retrospectively analyzed and
compared the clinical characteristics, toxicities, and survival of 143 patients
with stages III, IVA, and IVB head and neck cancer treated with concurrent CRT
according to their Glasgow prognostic score between 2007 and 2010. RESULTS: The
Glasgow prognostic score was correlated with advanced tumor stage and T/N
classification. Patients with a higher Glasgow prognostic score were less likely
to tolerate concurrent CRT, experienced more weight loss, required tube feeding
support more frequently, and had higher percentage of grade >=3 hematological
toxicities, sepsis, and toxic death. Patients with a Glasgow prognostic score of
0 had better overall and recurrence-free survival than those with a Glasgow
prognostic score of 1 or 2. CONCLUSION: Pretreatment Glasgow prognostic score
predicts treatment tolerance, toxicity, and survival in patients with advanced
head and neck cancer undergoing concurrent CRT.
PMID- 28688125
TI - Novel ex vivo training model for freehand insertion using a double-bending
peroral direct cholangioscope.
AB - BACKGROUND AND AIM: Several experts of direct peroral videocholangioscopy (D
PVCS) using a conventional ultraslim endoscope have reported its usefulness for
the diagnosis and therapy of biliary tract diseases. We have additionally
developed a dedicated double-bending D-PVCS technique for freehand scope
insertion. In this study, we developed an ex vivo training model for the freehand
double-bending D-PVCS technique and compared it with the technique using a
conventional ultraslim endoscope. METHODS: The ex vivo model was made for
training using a U-shape insertion pattern. A third prototype endoscope and an
ultraslim upper gastrointestinal endoscope were used. Two experts and nine non
experts performed D-PVCS using the freehand technique. RESULTS: The two experts
could not advance the tip of the endoscope to the hilar portion using the
freehand technique, but they could achieve technical successful insertion to the
hilar portion with the third prototype cholangioscope using the freehand
technique alone. The non-experts could not advance the tip of the endoscope to
the bile duct using the freehand technique. On the other hand, two (22.2%) non
experts could advance the tip of the third prototype cholangioscope using the
freehand technique before the training conducted by the experts. After the
training, all the non-experts could advance the tip of the third prototype
cholangioscope to the hilar portion. CONCLUSIONS: The novel ex vivo model using a
third prototype cholangioscope was useful for training in the use of the freehand
D-PVCS technique.
PMID- 28688126
TI - Coaxial Triple-Layered versus Helical Be6 B11- Clusters: Dual Structural
Fluxionality and Multifold Aromaticity.
AB - Two low-lying structures are unveiled for the Be6 B11- nanocluster system that
are virtually isoenergetic. The first, triple-layered cluster has a peripheral
B11 ring as central layer, being sandwiched by two Be3 rings in a coaxial
fashion, albeit with no discernible interlayer Be-Be bonding. The B11 ring
revolves like a flexible chain even at room temperature, gliding freely around
the Be6 prism. At elevated temperatures (1000 K), the Be6 core itself also
rotates; that is, two Be3 rings undergo relative rotation or twisting with
respect to each other. Bonding analyses suggest four-fold (pi and sigma)
aromaticity, offering a dilute and fluxional electron cloud that lubricates the
dynamics. The second, helix-type cluster contains a B11 helical skeleton
encompassing a distorted Be6 prism. It is chiral and is the first nanosystem with
a boron helix. Molecular dynamics also shows that at high temperature the helix
cluster readily converts into the triple-layered one.
PMID- 28688127
TI - Aminopyrazine Pathway to the Moco Metabolite Dephospho Form A.
AB - An efficient synthesis of the molybdopterin/molybdenum cofactor (Moco) oxidation
product dephospho Form A is described that assembles the pteridinone system
starting from an iodinated aminopyrazine. The sodium salt of dephospho Form A
could be purified by precipitation from methanol, which paved the way to the
title compound in the 100 mg range. By HPLC, the synthetic material was compared
with a sample isolated from a recombinant Moco containing protein. Analysis of
dephospho Form A is the only method that allows the quantification of the Moco
content of crude cell extracts and recombinant protein preparations.
PMID- 28688128
TI - Effects of fragmentation on the seed predation and dispersal by rodents differ
among species with different seed size.
AB - Fragmentation influences the population dynamics and community composition of
vertebrate animals. Fragmentation effects on rodent species in forests may, in
turn, affect seed predation and dispersal of many plant species. Previous studies
have usually addressed this question by monitoring a single species, and their
results are contradictory. Very few studies have discussed the fragmentation
effect on rodent-seed interaction among tree species with different seed sizes,
which can significantly influence rodent foraging preference and seed fate. Given
that fruiting periods for many coexisting plant species overlap, the changing
foraging preference of rodents may substantially alter plant communities. In this
study, we monitored the dispersal and predation by rodents of 9600 seeds,
belonging to 4 Fagaceae species with great variation in seed size, in both the
edge and interior areas of 12 tropical forest fragments ranging in area from 6.3
to 13872.9 ha in Southwest China. The results showed that forest fragmentation
altered the seed fates of all the species, but the intensity and even the
direction of fragmentation effect differed between species with large versus
small seeds. For the seeds harvested, fragment size showed negative effects in
forest interiors but positive effects at edges for the 2 large-seeded species,
but showed little effect for the 2 small-seeded species. For the seeds removed,
negative effects of fragment size only existed among the small-seeded species.
The different fragmentation effect on seed dispersal and predation among plant
species may, in turn, translate into the composition differences of the
regeneration of the whole fragmented forest.
PMID- 28688130
TI - The pharmaceutical industry needs more clinical pharmacologists.
PMID- 28688129
TI - Grazoprevir, ruzasvir, and uprifosbuvir for hepatitis C virus after NS5A
treatment failure.
AB - : People with hepatitis C virus (HCV) infection who have failed treatment with an
all-oral regimen represent a challenging treatment population. The present
studies evaluated the safety and efficacy of grazoprevir, ruzasvir, and
uprifosbuvir, with or without ribavirin, in participants who had failed an NS5A
inhibitor-containing regimen. C-SURGE (PN-3682-021) and C-CREST Part C (PN-3682
011 and -012) were open-label, multicenter studies. Participants who had
previously relapsed following an NS5A inhibitor-containing all-oral regimen were
retreated with grazoprevir 100 mg, ruzasvir 60 mg, and uprifosbuvir 450 mg alone
for 24 weeks or with ribavirin for 16 weeks. The primary efficacy endpoint was
sustained virologic response (HCV RNA below the limit of quantitation [<15
IU/mL]) 12 weeks after treatment completion (SVR12). In C-SURGE, SVR12 was
achieved by 49/49 (100%) and 43/44 (98%) genotype (GT)1 participants in the 24
week no ribavirin arm and the 16-week plus ribavirin arm (lost to follow-up, n =
1), respectively. In C-CREST Part C, SVR12 was achieved by 23/24 (96%)
participants treated for 16 weeks with ribavirin (GT1, 2/2 [100%]; GT2, 13/14
[93%]; GT3, 8/8 [100%]). One participant with GT2 infection discontinued study
medication after a single dose of grazoprevir, ruzasvir, and uprifosbuvir plus
ribavirin due to serious adverse events of vomiting and tachycardia. The presence
of baseline resistance-associated substitutions had no impact on SVR12. No
participant who completed treatment in either study experienced virologic
failure. CONCLUSION: Grazoprevir, ruzasvir, and uprifosbuvir, with or without
ribavirin, for 16 or 24 weeks was safe and highly effective in participants with
HCV infection who had previously failed NS5A inhibitor-containing therapy.
(Hepatology 2017;66:1794-1804).
PMID- 28688131
TI - A Consecutive C-H Functionalization Triggered by Oxidation of Active sp3 C-H
Bonds: Construction of 3,4-Dihydroquinoline-3-one Derivatives.
AB - We report a consecutive C-H functionalization that constructs 3,4
dihydroquinoline-3-one derivatives in high yields. This reaction is triggered by
oxidation of active sp3 C-H bonds of glycines and N-benzylanilines. In this
radical mediated transformation, four sp3 C-H bonds are functionalized
efficiently, together with construction of one heterocyclic ring with a
quaternary carbon center.
PMID- 28688132
TI - CRISPR-S: an active interference element for a rapid and inexpensive selection of
genome-edited, transgene-free rice plants.
PMID- 28688134
TI - Does scatter-hoarding of seeds benefit cache owners or pilferers?
AB - The scatter-hoarding behavior of granivorous rodents plays an important role in
seed dispersal and seedling regeneration of trees, as well as the evolution of
several well-known mutualisms between trees and rodents in forest ecosystems.
Because it is difficult to identify seed hoarders and pilferers under field
conditions by traditional methods, the full costs incurred and benefits accrued
by scatter-hoarding have not been fully evaluated in most systems. By using
infrared radiation camera tracking and seed tagging, we investigated the benefits
and losses of scatter-hoarded seeds (Camellia oleifera) for 3 sympatric rodent
species (Apodemus draco, Niviventer confucianus and Leopoldamys edwardsi) in a
subtropical forest of Southwest China during 2013 to 2015. We established the
relationships between the rodents and the seeds at the individual level. For each
rodent species, we calculated the cache recovery rate of cache owners, as well as
conspecific and interspecific pilferage rates. We found that all 3 sympatric
rodent species had a cache recovery advantage with rates that far exceeded
average pilferage rates over a 30-day tracking period. The smallest species (A.
draco) showed the highest rate of scatter-hoarding and the highest recovery
advantage compared with the other 2 larger species (N. confucianus and L.
edwardsi). Our results suggest that scatter-hoarding benefits cache owners in
food competition, supporting the pilferage avoidance hypothesis. Therefore,
scatter-hoarding behavior should be favored by natural selection, and plays a
significant role in species coexistence of rodent community and in the formation
of mutualism between seeds and rodents in forest ecosystems.
PMID- 28688133
TI - In silico evaluation of limited blood sampling strategies for individualized
recombinant factor IX prophylaxis in hemophilia B patients.
AB - : Essentials Individual pharmacokinetic (PK) parameters can be obtained by
limited sampling strategies (LSSs). Following 100 IU kg-1 rFIX, LSSs with 1 to 3
samples were evaluated in 5000 simulated subjects. For all LSSs, estimated
individual PK parameters showed acceptable bias and precision. One sample between
10 min-3 h and two between 48 h-56 h showed best predictive performance. SUMMARY:
Background Patients with severe hemophilia B regularly administer prophylactic
intravenous doses of clotting factor IX concentrate to maintain a trough level of
at least 0.01 IU mL-1 in order to prevent joint bleeds. Assessment of individual
pharmacokinetic (PK) parameters allows individualization of the recombinant
factor IX (rFIX) dose. Aim To evaluate the predictive performance of limited
sampling strategies (LSSs) with one to three samples to estimate individual PK
parameters of rFIX. Methods Monte Carlo simulations were performed to obtain 5000
concentration-time profiles by the use of population PK parameters for rFIX from
literature. Eleven LSSs were developed with one, two or three samples taken
within an 80-h interval following administration of 100 IU kg-1 rFIX. Clearance
(CL), half-life (t1/2 ), time to 1% and steady-state distribution volume (Vss )
were estimated for each simulated individual by the use of Bayesian analysis.
Results For each LSS, average bias was small for CL (range - 1.5% to 1.4%), t1/2
(range - 4.5% to - 0.7%), time to 1% (range - 2.9% to 0%), and Vss (range - 3.7%
to 0.3%). Imprecision for these parameters ranged from 6.4% to 11.9%, from 10.3%
to 15.6%, from 7.3% to 10.9%, and from 9% to 20.1%, respectively. The best
predictive performance was achieved with one sample taken between 10 min and 3 h
and two samples taken between 48 h and 56 h after administration of rFIX.
Conclusions This study demonstrates that limited sampling strategies, used for
individualized dosing of rFIX in hemophilia B patients, can be developed and
evaluated by in silico simulation.
PMID- 28688135
TI - "Lying-Down" Adrenal Sign: There Are Exceptions to the Rule Among Fetuses and
Neonates.
AB - A linear-shaped or "lying-down" adrenal gland is a sign often seen with the
absence of the kidney in the renal fossa due to renal agenesis, renal ectopia, or
horseshoe kidney. It is theorized that the presence of the kidney in the normal
location within the renal fossa is important for the formation of the normal
triangular inverted V or Y adrenal shape. There are exceptions to this rule
whereby a kidney is missing from the renal fossa, yet a normal adrenal shape is
present. This series looked at 18 cases of an empty renal fossa in fetal,
neonatal, and pediatric patients and recorded the shape of the adrenal gland.
Nine cases (50%) appropriately showed the linear or lying-down adrenal gland; 6
(33%) showed an exception to the rule, with a normally shaped adrenal gland; and
3 (17%) showed a pseudo exception in which the adrenal gland was linear but
blended with the diaphragmatic crus to simulate a triangular adrenal gland. The
sonographic characteristics of the crus are different from those of the adrenal
gland; thus, this pseudo exception can be avoided by careful inspection. Because
the absence of the kidney is often a difficult diagnosis, the lying-down adrenal
gland sign can be a helpful secondary sign for confirming that a kidney is absent
or ectopic in position and not within the renal bed.
PMID- 28688137
TI - Report of the International Journal of Urology Editorial Board Meeting and second
IJU Intensive Seminar "IJU Dojo (IJU School)" 2017 in Kagoshima, Japan.
PMID- 28688136
TI - Ultrasound Versus Traditional Palpation to Guide Radial Artery Cannulation in
Critically Ill Children: A Randomized Trial.
AB - OBJECTIVES: To identify success rates for radial artery cannulation in a
pediatric critical care unit using either palpation or ultrasound guidance to
cannulate the radial artery. METHODS: A prospective randomized comparative study
of critically ill children who required invasive monitoring in a tertiary
referral center was conducted. All patients were randomized by a stratified block
of 4 to either ultrasound-guided or traditional palpation radial artery
cannulation. The primary outcomes were the first attempt and total success rates.
RESULTS: Eighty-four children were enrolled, with 43 randomized to the palpation
technique and 41 to the ultrasound-guided technique. Demographic data between the
groups were not significantly different. The total success and first attempt
rates for the ultrasound-guided group were significantly higher than those for
the palpation group (success ratio, 2.03; 95% confidence interval, 1.13-3.64; P =
.018; and success ratio, 4.18; 95% confidence interval, 1.57-11.14; P = .004,
respectively). The median time to success for the ultrasound-guided group was
significantly shorter than that for the palpation group (3.3 versus 10.4 minutes;
P < .001). Cannulation complications were lower in the ultrasound-guided group
than the palpation group (12.5% versus 53.3%; P < .001). CONCLUSIONS: The
ultrasound-guided technique could improve the success rate and allow for faster
cannulation of radial artery catheterization in critically ill children.
PMID- 28688138
TI - Editorial Comment to Prevention of infectious complications after prostate biopsy
procedure.
PMID- 28688140
TI - Pro: Acute-on-chronic liver failure.
PMID- 28688141
TI - Incidence, predictive factors and impacts of acute kidney injury in cirrhotic
patients hospitalized for cellulitis.
AB - BACKGROUND & AIMS: Cellulitis is a common infection in patients with cirrhosis
but its impact on progression of liver disease has been hardly addressed. This
study examines the incidence of acute kidney injury (AKI), predictive factors and
its impacts on mortality in cirrhotic patients hospitalized for cellulitis.
METHODS: Retrospective data from cirrhotic patients hospitalized for cellulitis
over the period January 2006 to September 2015 were analysed. AKI was defined
according to revised criteria of the International Club of Ascites. RESULTS: A
total of 101 episodes of cellulitis were examined (70.3% men; mean age 60.6 +/-
13.6 years). Of patients, 27% met criteria for acute on chronic liver failure
(ACLF) (grade 1: 63%; grade 2: 22%; grade 3: 15%). AKI was recorded in 50.5%
(type 1: 67%; type 2: 19%; type 3: 14%). AKI was present on admission in 21 of
the 51 patients (41%) who developed it. In the remaining 30 patients (59%), AKI
appeared during hospitalization and its development was associated with a MELD
score >14 (70% vs 30%, P=.024). In-hospital mortality was 10% and all patients
who died had AKI. A high MELD score on admission, AKI and ACLF were associated
with in-hospital mortality (P<.05). One-month transplant-free survival was 84%
(70% vs 98% in patients with and without AKI, P=.001). CONCLUSIONS: In cirrhotic
patients, cellulitis is a serious infection that often leads to AKI and ACLF. AKI
is a strong predictor of mortality in this setting.
PMID- 28688142
TI - Is antibody to surface antigen associated with hepatitis B reactivation in
patients with resolved hepatitis B?
PMID- 28688144
TI - Minimally Invasive Surgery.
PMID- 28688143
TI - First-line vascular endothelial growth factor inhibitors for advanced renal cell
carcinoma and the impact of new agents entering the treatment paradigm.
PMID- 28688147
TI - Bullous pemphigoid following the replacement of vildagliptin with anagliptin.
PMID- 28688145
TI - Therapeutic concentrations of digitoxin inhibit endothelial focal adhesion kinase
and angiogenesis induced by different growth factors.
AB - BACKGROUND AND PURPOSE: Cardiac glycosides are Na+ /K+ -ATPases inhibitors used
to treat congestive heart failure and cardiac arrhythmias. Epidemiological
studies indicate that patients on digitalis therapy are more protected from
cancer. Evidence of a selective cytotoxicity against cancer cells has suggested
their potential use as anticancer drugs. The effect on angiogenesis of clinically
used cardiac glycosides has not been extensively explored. EXPERIMENTAL APPROACH:
We studied the effect of digoxin, digitoxin and ouabain on early events of the
angiogenic process in HUVECs. We determined HUVEC viability, proliferation,
migration and differentiation into capillary tube-like structures. We also tested
drug activity using an in vivo angiogenesis model. Activation of protein tyrosine
kinase 2 (FAK) and signalling proteins associated with the Na+ /K+ -ATPase
signalosome was determined by Western blotting. KEY RESULTS: Digitoxin and
ouabain (1-100 nM) inhibited HUVEC migration, concentration-dependently, without
affecting cell viability, while digoxin induced apoptosis at the same
concentrations. Digitoxin antagonized growth factor-induced migration and
tubularization at concentrations (1-25 nM) within its plasma therapeutic range.
The anti-angiogenic effect of digitoxin was confirmed also by in vivo studies.
Digitoxin induced Src, Akt and ERK1/2 phosphorylation but did not affect FAK
autophosphorylation at Tyr397 . However, it significantly inhibited growth factor
induced FAK phosphorylation at Tyr576/577 . CONCLUSIONS AND IMPLICATIONS:
Therapeutic concentrations of digitoxin inhibited angiogenesis and FAK activation
by several pro-angiogenic stimuli. These novel findings suggest a potential
repositioning of digitoxin as a broad-spectrum anti-angiogenic drug for diseases
where pathological angiogenesis is involved.
PMID- 28688146
TI - Exercise and NAFLD: Is it worth the effort?
PMID- 28688148
TI - Adipose-derived mesenchymal stem cells therapy for acute kidney injury induced by
ischemia-reperfusion in a rat model.
AB - Acute kidney injury (AKI) represents a group of complicated syndromes with a high
mortality rate. The administration of adipose-derived mesenchymal stem cells
(ADMSCs) has been tested as a possible treatment method for AKI. The long-term
evaluation of AKI induced by ischemia/reperfusion (IR) and the probable renal
protection of ADMSCs are limited. In this study we have established a rat AKI
model induced by IR and investigated the possible protective effects of ADMSCs.
Adult Sprague-Dawley (SD) rats were divided into three groups (n = 6/each group).
The MOCK group was as the normal control. Rats in the IR-AKI and IR-AKI+ADMSCs
groups were subjected to IR injury by clamping both renal pedicles for 40
minutes. Rats in the MOCK and IR-AKI groups were injected with PBS via the tail
vein as negative treatment controls. Rats in the IR-AKI+ADMSCs group received
ADMSCs therapy (2 * 106 cells were injected into the rats via the tail vein). We
found that ADMSC transplantation restored the pathologic morphology induced by IR
AKI to normal compared with the MOCK group, suggesting the reparative function of
ADMSCs in kidney tissues. Compared with IR-induced AKI alone, ADMSC treatment
significantly decreased the number of apoptotic cells, the level of total urinary
protein and serum creatinine, the expression of pro-inflammatory cytokines (IL-6,
TNF-alpha, IL-1beta, IFN-gamma, TNF-alpha, IFN-gamma, and TGF-beta), and the
inflammation-associated proteins (HGF and SDF1), but increased the expression of
the anti-inflammatory cytokine, IL-10, and the anti-apoptotic regulator, Bcl-2.
Our data have indicated that ADMSC transplantation may protect against IR-induced
AKI by anti-apoptotic and anti-inflammatory effects.
PMID- 28688149
TI - Proteoglycan 4 and hyaluronan as boundary lubricants for model contact lens
hydrogels.
AB - Clinical data show that in vitro contact lens friction is related to in vivo
comfort. Solutions of biological lubricants hyaluronan (HA) and proteoglycan 4
(PRG4, also known as lubricin) reduce friction at a cornea-polydimethylsiloxane
(PDMS) interface. The purpose of this study was to (1) determine if PRG4 can sorb
to and lubricate model contact lens materials and (2) assess the boundary
lubricating ability of PRG4 and HA compared to saline on model contact lens
materials. PRG4 was obtained from bovine cartilage culture and suspended in
saline at 300 ug/mL. N,N-Dimethylacrylamidetris (trimethylsiloxy) silane,
(DMAA/TRIS) and methacryloxypropyltris (trimethylsiloxy) silane (pHEMA/TRIS)
silicone hydrogels were prepared. A previously described in vitro eyelid-hydrogel
and cornea-hydrogel biomechanical friction test was used to determine boundary
lubricant effect. PRG4 sorption to the hydrogels was assessed using a soak-rinse
protocol and western blotting. PRG4 effectively lubricated both silicone hydrogel
materials and HA effectively lubricated pHEMA/TRIS, as indicated by a
statistically significant reduction in friction compared to the saline control
lubricant. An HA and PRG4 combination showed a synergistic effect for pHEMA/TRIS
and effectively lubricated DMAA/TRIS. Biological boundary lubricants HA and PRG4
were shown to effectively lubricate silicone hydrogels when in solution.
Additionally, HA and PRG4 showed synergistic lubrication for pHEMA/TRIS. The
purpose of this study was not to replicate the friction coefficients of contact
lenses, but rather to investigate lubricant-surface interactions for common
contact lens constituents. These findings contribute to the potential development
of biomolecule based lubricant drops for contact lens wearers. (c) 2017 Wiley
Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1329-1338,
2018.
PMID- 28688151
TI - Physical validation of a Monte Carlo-based, phantom-derived approach to computed
tomography organ dosimetry under tube current modulation.
AB - PURPOSE: To physically validate the accuracy of a Monte Carlo-based, phantom
derived methodology for computed tomography (CT) dosimetry that utilizes organ
doses from precomputed axial scans and that accounts for tube current modulation
(TCM). METHODS: The output of a Toshiba Aquilion ONE CT scanner was modeled,
based on physical measurement, in the Monte Carlo radiation transport code MCNPX
(v2.70). CT examinations were taken of two anthropomorphic phantoms representing
pediatric and adult patients (15-yr-old female and adult male) at various
energies, in which physical organ dose measurements were made using optically
stimulated luminescence dosimeters (OSLDs). These exams (chest-abdomen-pelvis)
were modeled using organ dose data obtained from the computationally equivalent
phantom of each anthropomorphic phantom. TCM was accounted for by weighting all
organ dose contributions by both the relative attenuation of the phantom and the
image-derived mA value (from the DICOM header) at the same z-extent (cranial
caudal direction) of the axial dose data. RESULTS: The root mean squares of
percent difference in organ dose when comparing the physical organ dose
measurements to the computational estimates were 21.2, 12.1, and 15.1% for the
uniform (no attenuation weighting), weighted (computationally derived), and image
based methodologies, respectively. CONCLUSIONS: Overall, these data suggest that
the Monte Carlo-based dosimetry presented in this work is viable for CT
dosimetry. Additionally, for CT exams with TCM, local attenuation weighting of
organ dose contributions from precomputed axial dosimetry libraries increases
organ dose accuracy.
PMID- 28688150
TI - National assessment of early hospitalization after liver transplantation: Risk
factors and association with patient survival.
AB - Hospitalization is known to occur frequently in the first 6 months following
liver transplantation (LT). Using a novel data linkage between the Scientific
Registry of Transplant Recipients and Centers for Medicare and Medicaid Services,
our study has 2 objectives: (1) to determine risk factors for "early"
hospitalization (ie, within 6 months of LT); and (2) to quantify the importance
of hospitalization history in the first 6 months with respect to subsequent
patient survival (ie, survival, conditional on surviving 6 months post-LT). The
study population consisted of patients aged >=18 years who underwent deceased
donor LT between January 1, 2003 and December 31, 2010, with Medicare as primary
or secondary insurance and were discharged alive from the index LT
hospitalization (n = 7220). The early hospitalization rate was 2.76 per patient
year and was significantly associated with many recipient factors (eg, recipient
age, hepatitis C, diabetes, poor renal function including dialysis, and recipient
of transjugular intrahepatic portosystemic shunt procedure before LT), as well as
donor race and donation after cardiac death. Conditional on surviving 6 months
after LT, the covariate-adjusted death rate increased by 22% for each additional
hospitalization occurring in the first 6 months (hazard ratio, 1.22; P < 0.001).
In conclusion, several LT recipient factors are significantly associated with
early hospitalization. Moreover, a patient's hospitalization profile during
follow-up months 0-6 is a very strong predictor of survival thereafter. Efforts
and resources should be devoted toward identifying LT recipients at risk for
early hospitalization and modifying the actionable risk factors such as hepatitis
C, diabetes, and body mass index to improve resource utilization and overall
outcomes. Liver Transplantation 23 1143-1152 2017 AASLD.
PMID- 28688152
TI - Effects of mesiodens on adjacent permanent teeth: a retrospective study in Korean
children based on cone-beam computed tomography.
AB - BACKGROUND: Mesiodens can be associated with several complications. The optimal
age for treatment, however, remains controversial. AIM: To investigate the three
dimensional (3D) positions of mesiodens using cone-beam computed tomography
(CBCT) and determine the association of eruption-related complications of
mesiodens with these 3D positions and delayed development of the central
incisors. DESIGN: In total, 293 Korean children (383 supernumerary teeth) aged 4
10 years with no history of orthodontic treatment were included. CBCT and
panoramic radiography data for all patients were retrospectively investigated
with regard to the 3D positions of mesiodens, apical maturity of the permanent
first molars, delayed development of the central incisors relative to the apical
maturity of the permanent first molars (Nolla's stage), and eruption-related
complications of mesiodens. RESULTS: Eruption-related complications were not
correlated with any 3D characteristic other than the 'within the arch' position
of mesiodens, while they showed a significant correlation with delayed
development of the central incisors (P < 0.05). CONCLUSIONS: Mesiodens caused
eruption-related complications in 33.7% patients. Moreover, the risk of these
complications was higher when mesiodens caused delayed development of the central
incisors. These findings can aid clinicians in planning appropriate and timely
treatment for mesiodens, with focus on minimising patient discomfort.
PMID- 28688153
TI - AQP4-knockout aggravation of isoprenaline-induced myocardial injury is mediated
by p66Shc and endoplasmic reticulum stress.
AB - Aquaporin 4 (AQP4) is a type of water channel protein that maintains the water
balance of cardiomyocytes. However, the physiological role of AQP4 in
cardiovascular disease is poorly understood. We wanted to explore whether p66Shc
and endoplasmic reticulum stress participates in AQP4 knockout (KO)-mediated
cardiac injury. There were two types of mice: AQP4 knockout and wild-type mice.
Each type was randomly divided into three groups: Control group, isoprenaline
stimulation group (ISO, 1 mg/kg, s.c., 5 days), and apocynin treatment group
(APO, 100 mg/kg, p.o., 3 days). H9c2 rat cardiomyocytes were cultured for RNA
interference of AQP4. Results showed increased left ventricular weight index and
more severe myocardial inflammation were induced in AQP4 knockout mice relative
to wild-type mice, accompanied by significantly increased levels of the oxidative
stress biomarkers MDA and NOX4. In addition, the expressions of p66Shc, ER stress
markers PERK, GRP78 and CHOP and proinflammatory factors such as ETA , IL6 and
TNFalpha were upregulated in the myocardium of AQP4 knockout mice or AQP4 siRNA
treated cardiomyocytes, whereas CASQ2 was downregulated. ISO stimulation
aggravated these abnormalities, which were significantly attenuated by apocynin.
This study showed that AQP4 knockout mice were susceptible to cardiac injury
induced by ISO. The mechanism was closely connected with p66Shc and
proinflammatory factors. Endoplasmic reticulum stress was also involved in the
pathological process.
PMID- 28688154
TI - High Efficiency MAPbI3 Perovskite Solar Cell Using a Pure Thin Film of
Polyoxometalate as Scaffold Layer.
AB - Here, we successfully used a pure layer of [SiW11 O39 ]8- polyoxomethalate (POM)
structure as a thin-film scaffold layer for CH3 NH3 PbI3 -based perovskite solar
cells (PSCs). A smooth nanoporous surface of POM causes outstanding improvement
of the photocurrent density, external quantum efficiency (EQE), and overall
efficiency of the PSCs compared to mesoporous TiO2 (mp-TiO2 ) as scaffold layer.
Average power conversion efficiency (PCE) values of 15.5 % with the champion
device showing 16.3 % could be achieved by using POM and a sequential deposition
method with the perovskite layer. Furthermore, modified and defect-free
POM/perovskite interface led to elimination of the anomalous hysteresis in the
current-voltage curves. The open-circuit voltage decay study shows promising
decrease of the electron recombination in the POM-based PSCs, which is also
related to the modification of the POM/ perovskite interface and higher electron
transport inside the POM layer.
PMID- 28688155
TI - Critical care management of the patient with cirrhosis awaiting liver transplant
in the intensive care unit.
AB - Patients with cirrhosis who are awaiting liver transplantation (LT) are at high
risk for developing critical illnesses. Current liver allocation policies that
dictate a "sickest first" approach coupled with a mismatch between need and
availability of organs result in longer wait times, and thus, patients are
becoming increasingly ill while awaiting organ transplantation. Even patients
with well-compensated cirrhosis may suffer acute deterioration; the syndrome of
acute-on-chronic liver failure (ACLF) results in multisystem organ dysfunction
and a marked increase in associated short-term morbidity and mortality. For
patients on transplant waiting lists, the development of multisystem organ
failure may eliminate candidacy for transplant by virtue of being "too sick" to
safely undergo transplantation surgery. The goals of intensive care management of
patients suffering ACLF are to rapidly recognize and treat inciting events (eg,
infection and bleeding) and to aggressively support failing organ systems to
ensure that patients may successfully undergo LT. Management of the critically
ill ACLF patient awaiting transplantation is best accomplished by
multidisciplinary teams with expertise in critical care and transplant medicine.
Such teams are well suited to address the needs of this unique patient population
and to identify patients who may be too ill to proceed to transplantation
surgery. The focus of this review is to identify the common complications of ACLF
and to describe our approach management in critically ill patients awaiting LT in
our centers. Liver Transplantation 23 1465-1476 2017 AASLD.
PMID- 28688156
TI - Comparison and Combination of Strain and Shear Wave Elastography of Breast Masses
for Differentiation of Benign and Malignant Lesions by Quantitative Assessment:
Preliminary Study.
AB - OBJECTIVES: To compare the diagnostic performance of strain and shear wave
elastography of breast masses for quantitative assessment in differentiating
benign and malignant lesions and to evaluate the diagnostic accuracy of combined
strain and shear wave elastography. METHODS: Between January and February 2016,
37 women with 45 breast masses underwent both strain and shear wave ultrasound
(US) elastographic examinations. The American College of Radiology Breast Imaging
Reporting and Data System (BI-RADS) final assessment on B-mode US imaging was
assessed. We calculated strain ratios for strain elastography and the mean
elasticity value and elasticity ratio of the lesion to fat for shear wave
elastography. Diagnostic performances were compared by using the area under the
receiver operating characteristic curve (AUC). RESULTS: The 37 women had a mean
age of 47.4 years (range, 20-79 years). Of the 45 lesions, 20 were malignant, and
25 were benign. The AUCs for elasticity values on strain and shear wave
elastography showed no significant differences (strain ratio, 0.929; mean
elasticity, 0.898; and elasticity ratio, 0.868; P > .05). After selectively
downgrading BI-RADS category 4a lesions based on strain and shear wave
elastographic cutoffs, the AUCs for the combined sets of B-mode US and
elastography were improved (B-mode + strain, 0.940; B-mode + shear wave; 0.964;
and B-mode, 0.724; P < .001). Combined strain and shear wave elastography showed
significantly higher diagnostic accuracy than each individual elastographic
modality (P = .031). CONCLUSIONS: These preliminary results showed that strain
and shear wave elastography had similar diagnostic performance. The addition of
strain and shear wave elastography to B-mode US improved diagnostic performance.
The combination of strain and shear wave elastography results in a higher
diagnostic yield than each individual elastographic modality.
PMID- 28688157
TI - The application of 3-dimensional printing for preoperative planning in oral and
maxillofacial surgery in dogs and cats.
AB - OBJECTIVE: To describe the application of 3-dimensional (3D) printing in advanced
oral and maxillofacial surgery (OMFS) and to discuss the benefits of this
modality in surgical planning, student and resident training, and client
education. STUDY DESIGN: Retrospective case series. ANIMALS: Client-owned dogs (n
= 28) and cats (n = 4) with 3D printing models of the skulls. METHODS: The
medical records of 32 cases with 3D printing prior to major OMFS were reviewed.
RESULTS: Indications for 3D printing included preoperative planning for
mandibular reconstruction after mandibulectomy (n = 12 dogs) or defect nonunion
fracture (n = 6 dogs, 2 cats), mapping of ostectomy location for
temporomandibular joint ankylosis or pseudoankylosis (n = 4 dogs), assessment of
palatal defects (n = 2 dogs, 1 cat), improved understanding of complex anatomy in
cases of neoplasia located in challenging locations (n = 2 dogs, 1 cat), and in
cases of altered anatomy secondary to trauma (n = 2 dogs). CONCLUSION: In the
authors' experience, 3D printed models serve as excellent tools for OMFS planning
and resident training. Furthermore, 3D printed models are a valuable resource to
improve clients' understanding of the pet's disorder and the recommended
treatment. CLINICAL RELEVANCE: Three-dimensional printed models should be
considered viable tools for surgical planning, resident training, and client
education in candidates for complex OMFS.
PMID- 28688158
TI - Determination of hepatocellular carcinoma grade by needle biopsy is unreliable
for liver transplant candidate selection.
AB - The objective of this article is to evaluate the utility of preoperative needle
biopsy (PNB) grading of hepatocellular carcinoma (HCC) as a biomarker for liver
transplantation (LT) candidate selection. Given the prognostic significance of
HCC tumor grade, PNB grading has been proposed as a biomarker for LT candidate
selection. Clinicopathologic characteristics of HCC LT recipients (1989-2014)
with a PNB were analyzed, and the concordance of PNB grade to explant grade and
vascular invasion was assessed to determine whether incorporation of PNB grade to
accepted transplant criteria improved candidate selection. Of 965 patients
undergoing LT for HCC, 234 (24%) underwent PNB at a median of 280 days prior to
transplant. Grade by PNB had poor concordance to final explant pathology (kappa =
0.22; P = 0.003), and low sensitivity (29%) and positive predictive value (35%)
in identifying poorly differentiated tumors. Vascular invasion was predicted by
explant pathologic grade (rs= 0.24; P < 0.001) but not PNB grade (rs = -0.05; P =
0.50). Increasing explant pathology grade (P = 0.02), but not PNB grade (P =
0.65), discriminated post-LT HCC recurrence risk. The incorporation of PNB grade
to the established radiologic Milan criteria (MC) did not result in improved
prognostication of post-LT recurrence (net reclassification index [NRI] = 0%),
whereas grade by explant pathology resulted in significantly improved
reclassification of risk (NRI = 19%). Preoperative determination of HCC grade by
PNB has low concordance with explant pathologic grade and low sensitivity and
positive predictive value in identifying poorly differentiated tumors. PNB grade
did not accurately discriminate post-LT HCC recurrence and had no utility in
improving prognostication compared with the MC alone. Incorporation of PNB to
guide transplant candidate selection appears unjustified. Liver Transplantation
23 1123-1132 2017 AASLD.
PMID- 28688159
TI - AAPM TG 158: Measurement and calculation of doses outside the treated volume from
external-beam radiation therapy.
AB - The introduction of advanced techniques and technology in radiotherapy has
greatly improved our ability to deliver highly conformal tumor doses while
minimizing the dose to adjacent organs at risk. Despite these tremendous
improvements, there remains a general concern about doses to normal tissues that
are not the target of the radiation treatment; any "nontarget" radiation should
be minimized as it offers no therapeutic benefit. As patients live longer after
treatment, there is increased opportunity for late effects including second
cancers and cardiac toxicity to manifest. Complicating the management of these
issues, there are unique challenges with measuring, calculating, reducing, and
reporting nontarget doses that many medical physicists may have limited
experience with. Treatment planning systems become dramatically inaccurate
outside the treatment field, necessitating a measurement or some other means of
assessing the dose. However, measurements are challenging because outside the
treatment field, the radiation energy spectrum, dose rate, and general shape of
the dose distribution (particularly the percent depth dose) are very different
and often require special consideration. Neutron dosimetry is also particularly
challenging, and common errors in methodology can easily manifest as errors of
several orders of magnitude. Task Group 158 was, therefore, formed to provide
guidance for physicists in terms of assessing and managing nontarget doses. In
particular, the report: (a) highlights major concerns with nontarget radiation;
(b) provides a rough estimate of doses associated with different treatment
approaches in clinical practice; (c) discusses the uses of dosimeters for
measuring photon, electron, and neutron doses; (d) discusses the use of
calculation techniques for dosimetric evaluations; (e) highlights techniques that
may be considered for reducing nontarget doses; (f) discusses dose reporting; and
(g) makes recommendations for both clinical and research practice.
PMID- 28688160
TI - Unilateral vocal cord paralysis after surgical closure of a patent ductus
arteriosus in extremely preterm infants.
AB - AIM: Left vocal cord paralysis (LVCP) is variably reported post ligation of
patent ductus arteriosus (PDA). Our objective was to determine the incidence of
LVCP and identify predictive factors and associated morbidities in preterm
infants post PDA ligation. METHODS: This is a retrospective cohort study of
infants less than 29 weeks gestational age from 2006 to 2014 who underwent PDA
ligation. Infants with laryngeal symptoms underwent flexible fibreoptic
nasopharyngolaryngoscopy to evaluate vocal cord function. We compared short- and
long-term morbidities among infants with and without symptomatic LVCP. RESULTS: A
total of 35 infants underwent PDA ligation in the study period, of which 11
infants (31%) developed symptomatic LVCP. Dysphonia was the presenting symptom in
all neonates with LVCP and stridor was present in 46% (5/11) of them. The median
(interquartile range) gestation (25 weeks (24-27) vs. 25 weeks (23-28)),
birthweight (810 g (550-1180) vs. 825 g (550-1220)) and age at surgery (19 days
(9-27) vs. 20 (5-69)) were similar in infants with and without LVCP,
respectively. Infants with LVCP took significantly longer to reach suck feeds
(128 vs. 90 days, P = <0.001), stayed longer in hospital (119 vs. 95 days, P =
0.01) and were more likely to go home on oxygen (73 vs. 27%; P = 0.024).
Neurodevelopmental outcomes were similar in the two groups. CONCLUSIONS: LVCP was
noted in 31% of infants post PDA ligation and was associated with prolonged
hospital stay, a longer time to reach suck feeds and a need for home oxygen. No
predictive factors for development of LVCP were identified.
PMID- 28688162
TI - Reply.
PMID- 28688163
TI - Direct Monofluoromethylthiolation with S-(Fluoromethyl) Benzenesulfonothioate.
AB - An electrophilic shelf-stable monofluoromethylthiolating reagent S-(fluoromethyl)
benezenesulfonothioate (1) was developed. In the presence of a copper catalyst,
reagent 1 coupled with a variety of aryl boronic acids to give the corresponding
monofluoromethylthiolated arenes in high yields. In addition, addition of reagent
1 to alkyl alkenes in the presence of a silver catalyst gave alkyl
monofluoromethylthioethers in high yields.
PMID- 28688161
TI - Identification of patients with cancer with a high risk to develop delirium.
AB - Delirium deteriorates the quality of life in patients with cancer, but is
frequently underdiagnosed and not adequately treated. In this study, we evaluated
the occurrence of delirium and its risk factors in patients admitted to the
hospital for treatment or palliative care in order to develop a prediction model
to identify patients at high risk for delirium. In a period of 1.5 years, we
evaluated the risk of developing delirium in 574 consecutively admitted patients
with cancer to our academic oncology department with the Delirium Observation
Screening Scale. Risk factors for delirium were extracted from the patient's
chart. A delirium prediction algorithm was constructed using tree analysis, and
validated with fivefold cross-validation. A total of 574 patients with cancer
were acutely (42%) or electively (58%) admitted 1733 times. The incidence rate of
delirium was 3.5 per 100 admittances. Tree analysis revealed that the
predisposing factors of an unscheduled admittance and a metabolic imbalance
accurately predicted the development of delirium. In this group the incidence
rate of delirium was 33 per 100 patients (1:3). The AUC of the model was 0.81,
and 0.65 after fivefold cross-validation. We identified that especially patients
undergoing an unscheduled admittance with a metabolic imbalance do have a
clinically relevant high risk to develop a delirium. Based on these factors, we
propose to evaluate preventive treatment of these patients when admitted to the
hospital in order to improve their quality of life.
PMID- 28688165
TI - Simultaneous vascularized lymph node transfer and carpal tunnel release for
treatment of advanced stage of breast cancer-related lymphedema with carpal
tunnel syndrome.
PMID- 28688166
TI - Triheptanoin for the treatment of brain energy deficit: A 14-year experience.
AB - Triheptanoin is an odd-chain triglyceride with anaplerotic properties-that is,
replenishing the pool of metabolic intermediates in the Krebs cycle. Unlike even
chain fatty acids metabolized to acetyl-CoA only, triheptanoin can indeed provide
both acetyl-CoA and propionyl-CoA, two key carbon sources for the Krebs cycle.
Triheptanoin was initially used in patients with long-chain fatty acid oxidation
disorders. The first demonstration of the possible benefit of triheptanoin for
brain energy deficit came from a patient with pyruvate carboxylase deficiency, a
severe metabolic disease that affects anaplerosis in the brain. In an open-label
study, triheptanoin was then shown to decrease nonepileptic paroxysmal
manifestations by 90% in patients with glucose transporter 1 deficiency syndrome,
a disease that affects glucose transport into the brain. 31 P magnetic resonance
spectroscopy studies also indicated that triheptanoin was able to correct
bioenergetics in the brain of patients with Huntington disease, a
neurodegenerative disease associated with brain energy deficit. Altogether, these
studies indicate that triheptanoin can be a treatment for brain energy deficit
related to altered anaplerosis and/or glucose metabolism. (c) 2017 Wiley
Periodicals, Inc.
PMID- 28688168
TI - 'Hidden identities': perceptions of sexual identity in Beijing.
AB - This article draws upon responses given by volunteers who work in the Beijing
LGBT Centre regarding perceptions of sexual identity, and how Chinese culture
affects hidden or open sexual identities of Chinese lesbian and gay people in
this region. The insights gained from those working carefully to create social
change offers an important and original contribution to the field of gay and
lesbian studies in China. The findings indicate the volunteers at the Beijing
LGBT Centre are frustrated by the lack of acceptance of non-heterosexual
relationships among Chinese culture and society, and by the disregard of lesbian
gay and bisexual (LGB) people by the Chinese government. The findings also
illustrate stigmatization of homosexuality in China is enacted in structural
terms (such as in the lack of policy, legislation and positive endorsement by
governmental and socio-political organizations), public expression (such as
negative attitudes, beliefs or reactions towards LGB people) and internalized
repression (through fear of stigmatization, and subsequent abuse due to negative
societal attitudes and discrimination). Influenced by the Chinese tradition of
conforming to group values, the findings from this study show that volunteers at
the Beijing LGBT Centre believe LGB people in China are generally hesitant to
disclose their sexual identities, and reject the idea that there had been a
collective shift in Chinese culture regarding increased acceptance of LGB people.
It also finds volunteers at the LGBT Centre in Beijing blame Chinese culture for
its lack of acceptance of non-heterosexual relationships, and state
stigmatization of homosexuality in China is due to deep-rooted cultural
homophobia.
PMID- 28688169
TI - Sequential Dy(OTf)3 -Catalyzed Solvent-Free Per-O-Acetylation and Regioselective
Anomeric De-O-Acetylation of Carbohydrates.
AB - Dysprosium(III) trifluoromethanesulfonate-catalyzed per-O-acetylation and
regioselective anomeric de-O-acetylation of carbohydrates can be tuned by
adjusting the reaction medium. In this study, the per-O-acetylation of
unprotected sugars by using a near-stoichiometric amount of acetic anhydride
under solvent-free conditions resulted in the exclusive formation of acetylated
saccharides as anomeric mixtures, whereas anomeric de-O-acetylation in methanol
resulted in a moderate-to-excellent yield. Reactions with various unprotected
monosaccharides or disaccharides followed by a semi-one-pot sequential conversion
into the corresponding acetylated glycosyl hemiacetal also resulted in high
yields. Furthermore, the obtained hemiacetals could be successfully transformed
into trichloroimidates after Dy(OTf)3 -catalyzed glycosylation.
PMID- 28688167
TI - Inhibition of hyaluronan synthesis attenuates pulmonary hypertension associated
with lung fibrosis.
AB - BACKGROUND AND PURPOSE: Group III pulmonary hypertension (PH) is a highly lethal
and widespread lung disorder that is a common complication in idiopathic
pulmonary fibrosis (IPF) where it is considered to be the single most significant
predictor of mortality. While increased levels of hyaluronan have been observed
in IPF patients, hyaluronan-mediated vascular remodelling and the hyaluronan
mediated mechanisms promoting PH associated with IPF are not fully understood.
EXPERIMENTAL APPROACH: Explanted lung tissue from patients with IPF with and
without a diagnosis of PH was used to identify increased levels of hyaluronan. In
addition, an experimental model of lung fibrosis and PH was used to test the
capacity of 4-methylumbeliferone (4MU), a hyaluronan synthase inhibitor to
attenuate PH. Human pulmonary artery smooth muscle cells (PASMC) were used to
identify the hyaluronan-specific mechanisms that lead to the development of PH
associated with lung fibrosis. KEY RESULTS: In patients with IPF and PH,
increased levels of hyaluronan and expression of hyaluronan synthase genes are
present. Interestingly, we also report increased levels of hyaluronidases in
patients with IPF and IPF with PH. Remarkably, our data also show that 4MU is
able to inhibit PH in our model either prophylactically or therapeutically,
without affecting fibrosis. Studies to determine the hyaluronan-specific
mechanisms revealed that hyaluronan fragments result in increased PASMC stiffness
and proliferation but reduced cell motility in a RhoA-dependent manner.
CONCLUSIONS AND IMPLICATIONS: Taken together, our results show evidence of a
unique mechanism contributing to PH in the context of lung fibrosis.
PMID- 28688170
TI - Influence of orthopedic reinforced gloves versus double standard gloves on
contamination events during small animal orthopedic surgery.
AB - OBJECTIVE: To determine the influence of orthopedic reinforced gloves on
contamination events during small animal orthopedic surgery. STUDY DESIGN:
Prospective randomized controlled trial SAMPLE POPULATION: Two hundred and thirty
seven pairs of orthopedic gloves (474 gloves) and 203 pairs of double standard
gloves (812 gloves) worn during 193 orthopedic procedures. METHODS: Primary and
assistant surgeons were randomized to wear either orthopedic reinforced gloves or
double gloves. Gloves were leak tested to identify perforations at the end of
procedures. Perforations detected intraoperatively or postoperatively were
recorded. A contamination event was defined as at least one perforation on either
hand for orthopedic reinforced gloves, or a perforation of both the inner and
outer glove on the same hand for double gloves. RESULTS: Baseline characteristics
between the 2 intervention groups were similar. There was no difference in
contamination events between the double-gloved and orthopedic gloved groups (OR =
0.95, 95% CI = 0.49-1.87, P = .89). The same percentage of contamination events
(8% glove pairs used) occurred in the double gloved group (17 contamination
events) and in the orthopedic gloved group (19 contamination events). The odds of
a contamination event increased by 1.02 (95% CI 1.01-1.03, P < .001) with each
additional minute of surgery. CONCLUSION: Orthopedic reinforced gloves and double
standard gloving were equally effective at preventing contamination events in
small animal orthopedic procedures. CLINICAL RELEVANCE: Surgeons reluctant to
double glove due to perceptions of decreased dexterity and discomfort may safely
opt for wearing orthopedic gloves, which may improve their compliance.
PMID- 28688171
TI - Diagnosis of Xeroderma pigmentosum variant in a young patient with two novel
mutations in the POLH gene.
AB - We describe the characterization of Xeroderma Pigmentosum variant (XPV) in a
young Caucasian patient with phototype I, who exhibited a high sensitivity to
sunburn and multiple cutaneous tumors at the age of 15 years. Two novel mutations
in the POLH gene, which encodes the translesion DNA polymerase eta, with loss of
function due to two independent exon skippings, are reported to be associated as
a compound heterozygous state in the patient. Western blot analysis performed on
proteins from dermal fibroblasts derived from the patient and analysis of the
mutation spectrum on immunoglobulin genes produced during the somatic
hypermutation process in his memory B cells, show the total absence of
translesion polymerase eta activity in the patient. The total lack of Poleta
activity, necessary to bypass in an error-free manner UVR-induced pyrimidine
dimers following sun exposure, explains the early unusual clinical appearance of
this patient.
PMID- 28688172
TI - Potential impact of the sewer system on the applicability of alcohol and tobacco
biomarkers in wastewater-based epidemiology.
AB - Understanding the actual consumption of alcohol and tobacco in the population is
important for forming public health policy. For this purpose, wastewater-based
epidemiology has been applied as a complementary method to estimate the overall
alcohol and tobacco consumption in different communities. However, the stability
of their consumption biomarkers - ethyl sulfate, ethyl glucuronide, cotinine, and
trans-3'-hydroxycotinine - in the sewer system has not yet been assessed. This
study aimed to conduct such assessment using sewer reactors mimicking conditions
of rising main, gravity sewer, and wastewater alone, over a 12-hour period. The
results show that cotinine and trans-3'-hydroxycotinine are relatively stable
under all sewer conditions while ethyl sulfate was only stable in wastewater
alone and gradually degraded in rising main and gravity sewer conditions. Ethyl
glucuronide quickly degraded in all reactors. These findings suggest that
cotinine and trans-3'-hydroxycotinine are good biomarkers to estimate tobacco
consumption; ethyl sulfate may be used as a biomarker to estimate alcohol
consumption, but its in-sewer loss should be accounted for in the calculation of
consumption estimates. Ethyl glucuronide, and probably most of glucuronide
compounds, are not suitable biomarkers to be used in wastewater-based
epidemiology due to their in-sewer instability.
PMID- 28688173
TI - Serial two-year follow-up after lymphaticovenular anastomosis for the treatment
of lymphedema.
AB - PURPOSE: Despite extensive previous investigations regarding the efficacy of
lymphaticovenular anastomosis (LVA) for the treatment of lymphedema, few studies
have reported the long-term clinical course of individual patients undergoing
LVA. The present study presented our experience of LVA and to report serial
postoperative courses. METHODS: A retrospective chart review was performed for 17
patients (2 male and 15 female) with lymphedema refractory to conservative
treatment who underwent LVA and were followed-up for at least postoperative 24
months. Mean age was 39 years. There were 7 cases with primary lymphedema and 10
with secondary lymphedema. Three patients had lymphedema in upper extremity and
the other 14 had lesions in lower extremity. Outcomes were evaluated via
qualitative assessment and quantitative volume measurement conducted
preoperatively and 6, 12, and 24 months postoperatively. RESULTS: LVA was
performed in the distal extremities with a mean number of 2.5 (1-3). No
postoperative complications developed. Average follow-up period was 41.8 months.
Of 17 patients, 10 showed improvement in excess volume consistently during the
follow-up period, whereas 3 patients exhibited temporary improvement at
postoperative 6 months and subsequent aggravation at the latter follow-ups. No
improvement was observed throughout the follow-up period in 4 patients. The
requirements of complex decongestive physical therapy significantly decreased
from 1.7 to 0.77 per patient per year. The frequency of cellulitis also decreased
from 0.31 to 0.16 per patient per year. CONCLUSION: Our results suggest that LVA
may have long-term effectiveness and provide a favorable clinical course in the
long term.
PMID- 28688175
TI - Discrimination between closely related synthetic cannabinoids by GC-Cold-EI-MS.
AB - Gas chromatography thermal-electron ionization mass spectrometry (GC-EI-MS) is an
established method for the identification of mind-altering substances and is
routinely used by forensic laboratories. However, some commonly analyzed drugs of
abuse, relating to the synthetic cannabinoids receptor agonist group (SCs), pose
a challenge for this conventional technique. As the molecular cation radicals of
many excited SCs are labile within the ion source, the relative abundance of the
molecular ions obtained by the GC-EI-MS is often too small to allow
discrimination of structurally related drugs. In contrast, the cold-electron
ionization (cold-EI) method allows the enhancement and clear identification of
the molecular ions, while maintaining the ability to compare unknown analytes
with comprehensive mass spectrum libraries. This technique was explored for mass
spectrometric identification and unambiguous differentiation of 15 emerging
synthetic cannabinoids found on the drug market in Israel and elsewhere. The
current method was demonstrated to discriminate pairs of closely related SCs: FUB
PB-22 and FDU-PB-22, and 5F-PB-22 and NM-2201. In addition, the dependence of the
molecular ion enhancement on the cold-EI parameters was examined. Finally,
analysis of SCs from seized street samples provided by the Israeli police
demonstrates the enhanced identification power of GC-cold-EI-MS.
PMID- 28688174
TI - trans-Lycopene from tomato juice attenuates inflammatory biomarkers in human
plasma samples: An intervention trial.
AB - SCOPE: The effect of carotenoids from tomato juice (TJ) on inflammatory
biomarkers was evaluated by performing a 4-week dose-response nutritional trial
in a population at high cardiovascular risk. METHODS AND RESULTS: An open,
prospective, randomized, cross-over, and controlled clinical trial was carried
out with 28 volunteers (mean age 69.7 +/- 3.1 years; mean BMI 31.5 +/- 3.6 kg/m2
) at high cardiovascular risk, which were assigned to consume daily for 4 weeks
in random order: 200 mL (LD) or 400 mL (HD) of TJ, or water as a control (C),
with a 21-day wash-out period between each intervention. Blood samples were
collected at baseline (B) and after each intervention. Endpoints included
significant changes in plasmatic carotenoids, and adhesion molecules ICAM-1, and
VCAM-1, as well as a tendency to decrease the chemokine IL-8. Compared to C,
concentration of ICAM-1, and VCAM-1 were significantly lower (p ? 0.001), after
each TJ intervention. Decreases were correlated remarkably with the trans
lycopene, while the other carotenoids present in TJ have presented a minor
association or no association with changes in these molecules. CONCLUSION: trans
Lycopene from TJ may attenuate the risk of cardiovascular disease by reducing the
concentration of important inflammatory molecules related to atherosclerosis.
PMID- 28688176
TI - A Novel Role for CAMKK1 in the Regulation of the Mesenchymal Stem Cell Secretome.
AB - Transplantation of adult stem cells into myocardial tissue after acute myocardial
infarction (AMI), has been shown to improve tissue recovery and prevent
progression to ischemic cardiomyopathy. Studies suggest that the effects of
mesenchymal stem cells (MSC) are due to paracrine factors released by MSC, as the
benefits of MSC can be achieved through delivery of conditioned media (CM) alone.
We previously demonstrated that downregulation of Dab2 enhances MSC cardiac
protein expression and improves cardiac function after AMI following MSC
engraftment. In order to define the molecular mechanisms that regulate MSC
secretome, we analyzed gene arrays in MSC following downregulation of Dab2 via
TGFbeta1 pretreatment or transfection with Dab2:siRNA or miR-145. We identified
23 genes whose expressions were significantly changed in all three conditions.
Among these genes, we have initially focused our validation and functional work
on calcium/calmodulin-dependent protein kinase kinase-1 (CAMKK1). We quantified
the effects of CAMKK1 overexpression in MSC following injection of CM after AMI.
Injections of CM from MSC with CAMKK1 over-expression correlated with an increase
in vascular density (CAMKK1 CM: 2,794.95 +/- 44.2 versus Control: 1,290.69 +/-
2.8 vessels/mm2 ) and decreased scar formation (CAMKK1 CM 50% +/- 3.2% versus
Control: 28% +/- 1.4%), as well as improved cardiac function. Direct
overexpression of CAMKK1 in infarcted tissue using a CAMKK1-encoding plasmid
significantly improved ejection fraction (CAMKK1: 83.2% +/- 5.4% versus saline:
51.7% +/- 5.8%. Baseline: 91.3% +/- 4.3%) and decreased infarct size after AMI.
Our data identify a novel role for CAMKK1 as regulator of the MSC secretome and
demonstrate that direct overexpression of CAMKK1 in infarcted cardiac tissue,
results in therapeutic beneficial effects. Stem Cells Translational Medicine
2017;6:1759-1766.
PMID- 28688177
TI - Renal vein dilation predicts poor outcome in patients with refractory cirrhotic
ascites.
AB - AIM: Renal venous hypertension is known to be associated with worsening of renal
function in patients with decompensated heart failure. Intra-abdominal
hypertension including cirrhotic ascites also leads to renal venous hypertension.
We aimed to clarify the effect of renal venous hypertension on cirrhotic ascites.
METHODS: Two hepatologists measured the left renal vein diameter in 142
consecutive patients with refractory cirrhotic ascites using non-contrast
computed tomography. The renal vein diameter was measured at the renal vein main
trunk and upstream of the confluence of collateral veins. RESULTS: The inter
observer agreements were high for the measurements of the left renal vein (r =
0.918, P < 0.001). The median overall survival for patients with renal vein
diameter >=11 mm was less than that for patients with renal vein diameter <11 mm
(P < 0.001; 2.5 vs. 32.0 months). One-year survival rates were 15.3% versus
66.4%. Multivariate analysis revealed renal vein diameter >=11 mm (hazard ratio,
2.94; P < 0.001; 95% confidence interval, 1.67-5.20) and a high Model for End
stage Liver Disease score combined with serum sodium level (MELD-Na) (hazard
ratio, 3.39; P < 0.001; 95% confidence interval, 2.00-5.74) were significant
independent predictors of mortality. CONCLUSIONS: Renal vein dilation is a risk
factor of mortality in patients with refractory cirrhotic ascites, independent of
the MELD-Na score.
PMID- 28688178
TI - Transcriptomic analysis identifies a role of PI3K-Akt signalling in the responses
of skeletal muscle to acute hypoxia in vivo.
AB - KEY POINTS: Changes in gene expression that occur within hours of exposure to
hypoxia in in vivo skeletal muscles remain unexplored. Two hours of hypoxia
caused significant down-regulation of extracellular matrix genes followed by a
shift at 6 h to altered expression of genes associated with the nuclear lumen
while respiratory and blood gases were stabilized. Enrichment analysis of mRNAs
classified by stability rates suggests an attenuation of post-transcriptional
regulation within hours of hypoxic exposure, where PI3K-Akt signalling was
suggested to have a nodal role by pathway analysis. Experimental measurements and
bioinformatic analyses suggested that the dephosphorylation of Akt after 2 h of
hypoxic exposure might deactivate RNA-binding protein BRF1, hence resulting in
the selective degradation of mRNAs. ABSTRACT: The effects of acute hypoxia have
been widely studied, but there are few studies of transcriptional responses to
hours of hypoxia in vivo, especially in hypoxia-tolerant tissues like skeletal
muscles. We used RNA-seq to analyse gene expression in plantaris muscles while
monitoring respiration, arterial blood gases, and blood glucose in mice exposed
to 8% O2 for 2 or 6 h. Rapid decreases in blood gases and a slower reduction in
blood glucose suggest stress, which was accompanied by widespread changes in gene
expression. Early down-regulation of genes associated with the extracellular
matrix was followed by a shift to genes associated with the nuclear lumen. Most
of the early down-regulated genes had mRNA half-lives longer than 2 h, suggesting
a role for post-transcriptional regulation. These transcriptional changes were
enriched in signalling pathways in which the PI3K-Akt signalling pathway was
identified as a hub. Our analyses indicated that gene targets of PI3K-Akt but not
HIF were enriched in early transcriptional responses to hypoxia. Among the PI3K
Akt targets, 75% could be explained by a deactivation of adenylate-uridylate-rich
element (ARE)-binding protein BRF1, a target of PI3K-Akt. Consistent decreases in
the phosphorylation of Akt and BRF1 were experimentally confirmed following 2 h
of hypoxia. These results suggest that the PI3K-Akt signalling pathway might play
a role in responses induced by acute hypoxia in skeletal muscles, partially
through the dephosphorylation of ARE-binding protein BRF1.
PMID- 28688179
TI - Resveratrol attenuates excessive ethanol exposure induced insulin resistance in
rats via improving NAD+ /NADH ratio.
AB - SCOPE: Resveratrol has been shown to improve insulin resistance via activating
the NAD+ -dependent deacetylase SIRT1, but the effects of resveratrol on ethanol
induced insulin resistance remain unclear. This study was designed to explore the
potential mechanism by which resveratrol ameliorated ethanol-induced insulin
resistance, focusing on its regulations on the ratio of NAD+ /NADH and SIRT1
expression. METHODS AND RESULTS: Male Sprague-Dawley rats were fed either control
or ethanol liquid diets containing 0.8, 1.6 and 2.4 g/kg.bw ethanol with or
without 100 mg/kg.bw resveratrol for 22 weeks. Resveratrol improved ethanol (2.4
g/kg.bw) induced reductions in insulin sensitivity, SIRT1 expression (51%, P <
0.05), NAD+ /NADH ratio (196%, P < 0.01) as well as the expression and activity
of ALDH2 while decreased the augmentations in the expression and activity of ADH
and CYP2E1. In primary rat hepatocytes, ethanol exposure (25 mmol/L, 24 h)
similarly decreased SIRT1 expression and NAD+ /NADH ratio (33%, P < 0.05; 32%, P
< 0.01), and 0.1 MUmol/L resveratrol treatment reversed these decreases and
inhibited the expressions of ADH and CYP2E1. CONCLUSION: Resveratrol exhibits
benefits against ethanol-induced insulin resistance via improving the ratio of
NAD+ /NADH to regulate SIRT1, which is associated with the modulation of ethanol
metabolism enzymes.
PMID- 28688180
TI - Effect of silver diamine fluoride (SDF) on the dentin-pulp complex: ex vivo
histological analysis on human primary teeth and rat molars.
AB - The aim of this study was to determine the effect of SDF on the dentin-pulp
complex using two models: teeth after SDF application (ex vivo) and experimental
animal molars. A descriptive study was performed using two models. In the first
model, primary teeth (ex vivo) with enamel-dentin caries, without pulp
involvement and previously treated with 38% SDF, were evaluated by means of two
techniques: (a) Scanning Electron Microscopy (SEM) and energy-dispersive X-ray
detector (EDS) to determine qualitative and quantitative composition, and (b)
brightfield optical microscopy (OM) after decalcification. The second model used
laboratory animal molars from 12 male Wistar rats. Standardized enamel-dentin
cavities approximately 0.5 mm deep were made the distal fossa of the occlusal
face of both first lower molars, to one of which a 38% SDF solution was applied,
while the other was used as a control. Histological sections were prepared and
dental pulp was evaluated qualitatively in both groups. SEM on ex vivo teeth
showed areas of hypermineralization in the intertubular dentin and few blocked
tubules, while EDS detected Ag in the center of the lesion (7.34%), its
concentration declining at the edges (1.71%), with none in the areas farthest
from the lesion. OM showed SDF sealing the tubules only at the site where it had
been placed, with limited penetration beneath, the tubules appeared normal and
the pulp tissue associated to treated caries showed chronic inflammatory
infiltrate and formation of tertiary dentin, with no Ag precipitate. In the
experimental animal model, pulp histology was not significantly altered in the
molar cavities exposed to SDF. The observations using the different techniques on
dental tissues suggest that SDF causes minimal adverse effects. The results of
this study may contribute to further studies on the suitability of SDF as a cost
effective strategy for treating caries.
PMID- 28688181
TI - Surface detail reproduction and dimensional accuracy of molds: influence of
disinfectant solutions and elastomeric impression materials.
AB - This study compared the surface detail reproduction and dimensional accuracy of
molds after disinfection using 2% sodium hypochlorite, 2% chlorhexidine
digluconate or 0.2% peracetic acid to those of molds that were not disinfected,
for four elastomeric impression materials: polysulfide (Light Bodied Permlastic),
polyether (Impregum Soft), polydimethylsiloxane (Oranwash L) andpolyvinylsiloxane
(Aquasil Ultra LV). The molds were prepared on a matrix by applying pressure,
using a perforated metal tray. The molds were removed following polymerization
and either disinfected (by soaking in one of the solutions for 15 minutes) or not
disinfected. The samples were thus divided into 16 groups (n=5). Surface detail
reproduction and dimensional accuracy were evaluated using optical microscopy to
assess the 20-MUm line over its entire 25 mm length. The dimensional accuracy
results (%) were subjected to analysis of variance (ANOVA) and the means were
compared by Tukey's test (a=5%). The 20-MUm line was completely reproduced by all
elastomeric impression materials, regardless of disinfection procedure. There was
no significant difference between the control group and molds disinfected with
peracetic acid for the elastomeric materials Impregum Soft (polyether) and
Aquasil Ultra LV (polyvinylsiloxane). The high-level disinfectant peracetic acid
would be the choice material for disinfection.
PMID- 28688182
TI - Analysis of the adverse events reported to the office of the clinical director at
a dental school in Bogota, Colombia.
AB - Dentistry is interested in identifying and controlling adverse events, understood
as involuntary injuries to the patient during dental care. The aim of this study
was to analyze the adverse events reported to the Office of the Clinical Director
at the School of Dentistry at Pontificia Universidad Javeriana (Colombia) during
2011-2012. It was an observational, descriptive study that evaluated 227 dental
clinical records of patients who filed a complaint with the Office of the
Clinical Director. Of these, 43 were adverse events and were used as the basis
for this study. Of the 16,060 patients who received care during 2011 - 2012,
0.26% (43) filed a complaint involving an adverse event, of which 97.7 % were
considered preventable. Most of these (76.18%, n= 32) occurred during clinical
management of treatments in different specialties, 9.5% (4) were the result of
deficient external dental laboratory quality, and 14.32% (6) were due to failure
in document management, soft tissue injury, misdiagnosis and swallowing foreign
objects. Of the patients involved, 65.2% (28) received care from postgraduate
students, with the highest number of cases in the Oral Rehabilitation speciality.
The occurrence of adverse events during dental care, indicates the need for
information about their origin in order to establish protection barriers and
prevent their incidence, particularly in the educational area under the student
dental clinic service model.
PMID- 28688183
TI - Evaluation of pH and calcium ion diffusion from calcium hydroxide pastes and MTA.
AB - The aim of this ex vivo study was to evaluate changes in pH and calcium ion
diffusion through root dentin from calcium hydroxide (Ca (OH) 2) and mineral
trioxide aggregate (MTA) pastes at 7, 30 and 60 days; and the relationship
between pH and ion diffusion. Thirty-two human premolars were used. Crowns were
sectioned and root canals instrumented and filled in with the following
preparations: 1) Ca(OH) 2 + distilled water (n=7); 2) Ca(OH) 2 + 0.1%
chlorhexidine gluconate (n=7); 3) MTA + distilled water (n=7); 4) MTA + 0.1%
chlorhexidine gluconate (CHX) (n=7); 5) distilled water (n=2) (control); 6) 0.1%
chlorhexidine gluconate (n=2) (control). The apex and coronary opening were
sealed with IRM. Roots were placed in Eppendorf tubes with 1 ml distilled water
at 37 degrees C and 100% humidity. At baseline, 7, 30 and 60 days, pH was
measured with pH meter, and calcium ion content in the solution was analyzed by
atomic absorption spectrophotometry. The data were statistically analyzed using
ANOVA, simple linear regression analysis and Pearson's correlation test. The
highest pH values were achieved with calcium hydroxide pastes at 60 days (p <=
0.05). Calcium ions were released in all groups. The calcium hydroxide paste with
distilled water at 60 days had the highest calcium ion value (p <= 0.01). There
was a positive correlation between calcium and pH values.
PMID- 28688185
TI - Methodological aspects in the study of periodontal breakdown in rats: influence
of the presence and time of ligature.
AB - The aim of the present work was to evaluate the effect of different times on
alveolar bone loss (ABL) and whether the presence of ligature on one side affects
ABL on the contralateral site. This is a secondary analysis of databases from
studies conducted at the Federal University of Rio Grande do Sul. Included
studies used ligature-induced periodontal disease in rats. In order to be
included, the studies were required to have a control group without any ligatures
and an intra-group control. Three studies were included, which used different
time periods: 2 weeks with ligature and 8 weeks without ligature; 5 weeks with
ligature and 17 weeks without ligature; 22 weeks with and without ligature.
Animals were raised similarly and sacrificed by decapitation. Maxillae were
defleshed with 9% sodium hypochlorite. Pictures were taken and five measurements
were obtained from each image. The presence of ligature generated significantly
greater ABL compared to sides without ligature. Comparing sides with ligature,
ABL was lower at 2 weeks than at 5 and 22 weeks. Sides without ligature showed no
significant difference between 8 and 17 weeks for spontaneous periodontitis.
However, after 22 weeks, animals exhibited significantly greater ABL when
compared to other periods. The presence of ligature on one side did not influence
ABL on the contralateral side. Two weeks of ligature-induced periodontal disease
seems to be sufficient to demonstrate significant ABL. Teeth without ligature
contralateral to teeth with ligature may be considered sound controls, thereby
reducing the amount of animals needed in periodontal research.
PMID- 28688184
TI - Root surface temperature variation during mechanical removal of root canal
filling material. An in vitro study.
AB - The aim of this study was to analyze in vitro temperature changes on the outer
surface of the dental root during mechanical filling removal procedures. Thirty
recently extracted single-rooted lower premolars were cut transversally at 16 mm
from the apex in order to standardize sample length. Endodontic treatment was
performed on them. The filling material was subsequently removed using Gates
Glidden (G1, G2, G3); Peeso (P1, P2, P3) and PostecPlus FRC (FRC) reamers while
temperatures were measured on the outer surface using a digital device with
thermocouple at 0, 2, 4, 6, 8, 10 and 15 seconds. Temperatures were compared
using repeated measures ANOVA followed by pairwise comparison with Tukey's test.
All reamers caused significant temperature variation between different times
(p<0.05). Pairwise comparisons indicated that temperature increased with time for
all reamers (p<0.05). Significant differences in temperature were found between
different reamers after 0, 2, 4, 6, 8,10 and 15 seconds (p<0.05). Temperature at
the root surface increased considerably. Values higher than 50 degrees C were
recorded, the greatest increase from baseline being 16 degrees C. Accordingly, if
the procedure were begun at 37 degrees C (physiological temperature), the
temperature in the surrounding tissues - cementum, periodontium and bone - would
rise to 53 degrees C. An increase in 10 degrees C above body temperature at the
root surface may cause lesions in surrounding tissues. While removing filling
material, it is essential to cool, control action time and use instruments in
perfect condition, all of which may contribute to reducing the heat generated and
transmitted to the outer root surface.
PMID- 28688186
TI - Fermentation and purification strategies for the production of betulinic acid and
its lupane-type precursors in Saccharomyces cerevisiae.
AB - Microbial production of plant derived, biologically active compounds has the
potential to provide economic and ecologic alternatives to existing low
productive, plant-based processes. Current production of the pharmacologically
active cyclic triterpenoid betulinic acid is realized by extraction from the bark
of plane tree or birch. Here, we reengineered the reported betulinic acid pathway
into Saccharomyces cerevisiae and used this novel strain to develop efficient
fermentation and product purification methods. Fed-batch cultivations with
ethanol excess, using either an ethanol-pulse feed or controlling a constant
ethanol concentration in the fermentation medium, significantly enhanced
production of betulinic acid and its triterpenoid precursors. The beneficial
effect of excess ethanol was further exploited in nitrogen-limited resting cell
fermentations, yielding betulinic acid concentrations of 182 mg/L, and total
triterpenoid concentrations of 854 mg/L, the highest concentrations reported so
far. Purification of lupane-type triterpenoids with high selectivity and yield
was achieved by solid-liquid extraction without prior cell disruption using polar
aprotic solvents such as acetone or ethyl acetate and subsequent precipitation
with strong acids. This study highlights the potential of microbial production of
plant derived triterpenoids in S. cerevisiae by combining metabolic and process
engineering.
PMID- 28688187
TI - Reexamining opportunities for therapeutic protein production in eukaryotic
microorganisms.
AB - Antibodies are an important class of therapeutics and are predominantly produced
in Chinese Hamster Ovary (CHO) cell lines. While this manufacturing platform is
sufficiently productive to supply patient populations of currently approved
therapies, it is unclear whether or not the current CHO platform can address two
significant areas of need: affordable access to biologics for patients around the
globe and production of unprecedented quantities needed for very large
populations of patients. Novel approaches to recombinant protein production for
therapeutic biologic products may be needed, and might be enabled by non
mammalian expression systems and recent advances in bioengineering. Eukaryotic
microorganisms such as fungi, microalgae, and protozoa offer the potential to
produce high-quality antibodies in large quantities. In this review, we lay out
the current understanding of a wide range of species and evaluate based on
theoretical considerations which are best poised to deliver a step change in cost
of manufacturing and volumetric productivity within the next decade.Related
article: http://onlinelibrary.wiley.com/doi/10.1002/bit.26383/full.
PMID- 28688188
TI - Quality indicators of laryngeal cancer care in commercially insured patients.
AB - OBJECTIVE: To examine associations between quality, complications, and costs in
commercially insured patients treated for laryngeal cancer. STUDY DESIGN:
Retrospective cross-sectional analysis of MarketScan Commercial Claim and
Encounters data (Truven Health Analytics, Ann Arbor, Michigan, U.S.A.). METHODS:
We evaluated 10,969 patients diagnosed with laryngeal cancer from 2010 to 2012
using cross-tabulations and multivariate regression. Using quality indicators
derived from guidelines for recommended care, summary measures of quality were
calculated for diagnosis, initial treatment, surveillance, treatment for
recurrence, performance, and an overall summary measure of quality. RESULTS:
Higher-quality care in the initial treatment period was associated with lower
odds of 30-day mortality (odds ratio [OR] = 0.21, 95% confidence interval [CI]
[0.04-0.98]), surgical complications (OR = 0.39 [0.17-0.88]), and medical
complications (OR = 0.68 [0.49-0.96]). Mean incremental 1-year costs were higher
for higher-quality diagnosis ($20,126 [$14,785-$25,466]), initial treatment
($17,918 [$10,481-$25,355]), and surveillance ($25,424 [$20,014-$30,834]) quality
indicators, whereas costs were lower for higher-quality performance measures (
$45,723 [-$56,246--$35,199]) after controlling for all other variables. Higher
quality care was associated with significant differences in mean incremental
costs for initial treatment in surgical patients ($-37,303 [-$68,832--$5,775]),
and for the overall summary measure of quality in patients treated nonoperatively
($10,473 [$1,121-$19,825]). After controlling for the overall summary measure of
quality, costs were significantly lower for patients receiving high-volume
surgical care (mean -$18,953 [-$28,381--$9,426]). CONCLUSION: Higher-quality
larynx cancer care in commercially insured patients was associated with lower 30
day mortality and morbidity. High-volume surgical care was associated with lower
1-year costs, even after controlling for quality. These data have implications
for discussions of value and quality in an era of healthcare reform. LEVEL OF
EVIDENCE: 2c. Laryngoscope, 127:2805-2812, 2017.
PMID- 28688189
TI - Revision rates and time to revision following endoscopic sinus surgery: A large
database analysis.
AB - OBJECTIVES/HYPOTHESIS: Endoscopic sinus surgery (ESS) is performed for patients
with chronic rhinosinusitis (CRS) that have failed maximal medical therapy. This
study seeks to determine the prevalence of revision surgery and factors
predicting the need for revision after ESS using a large statewide surgery
database. STUDY DESIGN: Large retrospective cohort study using the State
Ambulatory Surgery Database for the state of California between 2005 and 2011.
METHODS: We identified over 61,000 patients with CRS who underwent ESS,
determined by Current Procedural Terminology code. We identified which patients
underwent a repeat surgery, and performed multivariable modeling to determine
which factors (nasal polyps, age, gender, insurance, hospital setting, ethnicity)
predicted the need for revision. Adjusted odds ratios (AOR) and 95% confidence
intervals are presented. RESULTS: Of 61,339 patients who underwent ESS, 4,078
(6.65%) returned for revision ESS during the time period investigated. In a
multivariable logistic regression model, positive predictors of revision were a
diagnosis of nasal polyps (AOR: 1.20, 95% CI: 1.11-1.29, P < .001) and female
gender (AOR: 1.20, 95% CI: 1.11-1.29, P < .001); public insurance was marginally
predictive of increased reoperation (AOR: 1.10, 95% CI: 1.00-1.21, P = .048).
Patients of Hispanic ethnicity were less likely to have revision surgery (AOR:
0.86, 95% CI: 0.77-0.97, P = .011). Age, income, and hospital setting were not
significant predictors. CONCLUSIONS: A minority of patients with CRS who undergo
ESS will have a revision surgery. This likelihood is increased in female patients
and those with nasal polyps, and decreased in patients of Hispanic ethnicity,
even when controlling for income, insurance, and hospital setting. LEVEL OF
EVIDENCE: 4. Laryngoscope, 128:31-36, 2018.
PMID- 28688190
TI - Improvement of glycemic state among responders to Sofosbuvir-based treatment
regimens: Single center experience.
AB - Chronic HCV infection has emerged as a complex multifaceted disease with
manifestations extending beyond the liver. HCV plays a direct role in glucose
metabolism leading to both insulin resistance and type 2 diabetes. To evaluate
the changes in the glycemic state following Sofosbuvir-based treatment regimens
in diabetic HCV patients. Four hundred chronic hepatitis C patients who underwent
Sofosbuvir-based treatment regimens were retrospectively screened. Sixty-five
diabetic HCV patients only enrolled in our analysis. Baseline demographic and
laboratory data were recorded. Pretreatment Transient elastography was performed.
At 24-week post EOT (SVR24), Fasting Plasma glucose, and Hemoglobin A1c were re
evaluated and compared with baseline. All enrolled diabetic patients were
responders. They showed statistically significant decline in Fasting Plasma
glucose and Hemoglobin A1c values at SVR24. Whatever the degree of hepatic
fibrosis, the level of Fasting Plasma glucose and Hemoglobin A1c decreased at
SVR24 in comparison to baseline level. Fifty-one patients showed improvement in
their Hemoglobin A1c values at SVR24 and this improvement was more likely to
occur among patients with low Body mass index. The reduction in Fasting Plasma
glucose >20 mg/dL (>1.1 mmol/L) and Hemoglobin A1c >=0.5% was not associated with
age, gender or hepatic fibrosis stage. Sofosbuvir-based regimens are a highly
efficient antiviral therapy for diabetic chronic HCV patients resulted in
improvement in Fasting Plasma glucose and Hemoglobin A1c.
PMID- 28688191
TI - Long-term native liver survival in infants with biliary atresia and use of a
stool color card: Case-control study.
AB - BACKGROUND: So far, there has been no epidemiological study on whether long-term
native liver survival (NLS) in infants with biliary atresia (BA) is associated
with use of a stool color card (SCC). METHODS: A case-control study was
performed, involving two associations for patients with BA in Japan. Participants
were patients with BA who were born and underwent their first open Kasai
procedures (KP) between August 1994 and March 2011, and who were also members of
either of two associations for patients with BA in Japan. SCC users were
classified as cases and SCC non-users as controls. RESULTS: Mean age at the time
of the first open KP was 59.7 and 68.2 days in SCC users and non-users,
respectively (P < 0.05). According to Kaplan-Meier analysis, the probability of
NLS at 12.5 years was 48.5% and 36.6% in SCC users and non-users (P < 0.05),
respectively. On Cox proportional hazard modeling, not using an SCC was harmful
to long-term NLS (hazard ratio, 2.61; 95% CI: 1.20-5.70; P = 0.016), adjusted for
sex, age of timing of KP and type of BA. CONCLUSIONS: Long-term NLS is associated
with SCC for early detection, but not associated with age or a threshold of age
at KP (<90 days) in patients with BA.
PMID- 28688192
TI - Assessment of human papillomavirus awareness in association with head and neck
cancer at a screening event.
AB - OBJECTIVES/HYPOTHESIS: To assess the baseline awareness of human papillomavirus
(HPV) infection as a cause of head and neck cancer (HNC) to design improved
targeted screening and education efforts. STUDY DESIGN: Retrospective review of
collected survey at a cancer screening event. METHODS: This was a screening event
at three hospitals and one community center in Miami, Florida. Participants were
recruited throughout the Greater Miami area. Descriptive statistics were used to
summarize the demographic characteristics of those who were aware of HPV and
those who were not. Adjusted odds ratios, odds ratios, and chi2 tests were used
in statistical analysis. RESULTS: A total of 196 women and 112 men were screened
across four sites, with 187 participants at hospital-based events and 124
participants at the community-based event. Forty percent of respondents had heard
of HPV, and 28.0% identified HPV as a risk factor for HNC. Non-Hispanic and
Hispanic respondents were 3.309 and 2.445 times, respectively, more likely than
Haitian respondents to have heard of HPV. Women were 2.488 times more likely than
men to be aware of HPV. College graduates were 2.268 times more likely than those
with less than a college degree to be aware of HPV. Younger respondents were more
likely to be aware of HPV. Of those who identified HPV as a risk factor for HNC,
95.4% also correctly identified smoking and 75.9% also correctly identified
alcohol as risk factors. CONCLUSIONS: Disparities in HPV and HNC awareness were
noted between gender, age, education level, and ethnicity. LEVEL OF EVIDENCE: NA.
Laryngoscope, 128:386-392, 2018.
PMID- 28688193
TI - Knockdown of lncRNA HULC inhibits proliferation, migration, invasion, and
promotes apoptosis by sponging miR-122 in osteosarcoma.
AB - Osteosarcoma is a rare malignant bone tumor with high degree of malignancy. HULC
(highly upregulated in liver cancer), a long noncoding RNA (lncRNA) was involved
in hepatocellular carcinoma development and progression, but its underlying
mechanism in osteosarcoma is unknown. The aim of this study was to explore the
functional role of HULC in osteosarcoma. The study was conducted in human
osteosarcoma cell lines and the expression of HULC in the cell lines was detected
by qRT-PCR. Furthermore, the effects of HULC on tumorigenicity of osteosarcoma
cells were evaluated by in vitro assays. Results revealed that HULC was highly
expressed in osteosarcoma MG63 and OS-732 cells compared to osteoblast hFOB1.19
cells. Suppression of HULC in osteosarcoma cells inhibited cell viability,
migration, invasion, and promoted apoptosis. HULC functioned as an endogenous
sponge for miR-122, and its silence functioned through upregulating miR-122.
HNF4G was a target of miR-122, and the effect of HNF4G on OS-732 cells was the
same as HULC. Furthermore, overexpression of miR-122 inactivated PI3K/AKT,
JAK/STAT, and Notch pathways by downregulation of HNF4G. These findings suggest
that knockdown of HULC inhibited proliferation, migration, and invasion by
sponging miR-122 in osteosarcoma cells. HULC may act as a novel therapeutic
target for management of osteosarcoma.
PMID- 28688194
TI - High mitochondrial DNA copy number was associated with an increased gastric
cancer risk in a Chinese population.
AB - Mitochondrial DNA (mtDNA) copy number (mtCN) may be a potential biomarker in
relation to cancer risk. However, the role of mtCN in gastric cancer remains
uncertain. We examined the association between peripheral blood leukocytes mtCN
level and gastric cancer risk in a case-control study including 984 gastric
cancer cases and 984 controls. We measured relative mtCN level by real-time
quantitative PCR-based assay, and used logistic regression models to assess the
association between mtCN and risk of gastric cancer. The mtCN level in gastric
cancer cases was significantly higher than that in controls (median value: 6.53
vs 4.12, P = 1.79 * 10-5 ). Compared with those with low mtCN, the risk for
gastric cancer was 1.29 (95% confidence interval [CI] = 1.02-1.63) in the median
group and 1.74 (95%CI = 1.39-2.18) in the high mtCN group (P for trend = 1.51 *
10-6 ). Because relative telomere length (RTL) has been associated with gastric
cancer risk in our previous study, we also evaluated the combined effects of mtCN
and RTL on gastric cancer risk. Multivariable regression model revealed that the
effects of mtCN and RTL were independent on gastric cancer risk. Compared with
those in the lowest risk group by combining mtCN and RTL, the odds ratio for
gastric cancer was 4.30 (95%CI = 2.79-6.63) in the highest risk group. Our
results suggest that mtDNA may be implicated in gastric carcinogenesis and mtCN
as well as RTL may serve as joint susceptible biomarkers for gastric cancer.
PMID- 28688195
TI - Physiology of biodeterioration on canvas paintings.
AB - The study of the physiological action of microorganisms in artistic materials is
one of the most interesting topics in biodeterioration nowadays. Pathologies and
illnesses of organic and inorganic materials provoked by microorganisms can be
treated by experts by a variety of preventive interventions. Artistic medicine
encompasses the monitoring of the exhibition and storage of art, as well as
proper environmental conditions and the regular cleaning of museums.
Biodeterioration control is essential in order to prevent fungal and bacterial
contamination in artwork. Biodeterioration of canvas paintings is a complex
phenomenon, not well-known at the moment. Canvas paintings are created by several
artistic techniques on textile supports that are not always kept in the best
conditions, and the best parameters of preventive conservation are often not
applied. Therefore, we need to research the agents and the main causes that
provoke canvas painting biodeterioration. By applying new methodologies, we can
identify the alterations and the treatments needed in order to manage the diverse
materials employed in artwork correctly. Herein, we review the causes of
biodeterioration that affect artwork, especially art created on textile supports.
We also study the alterations of the natural filmogenic materials employed in
traditional pictorial techniques, such as agglutinants and protection layers, and
the biodeterioration agents that impact them. Additionally, we review current
scientific methods employed for the identification of microbial species, and the
types of alterations of the materials where the organisms grow. Finally, we
summarize the different biocides and preventive conservation treatments that are
currently employed.
PMID- 28688196
TI - Typical antimicrobials induce mast cell degranulation and anaphylactoid reactions
via MRGPRX2 and its murine homologue MRGPRB2.
AB - Mast cells are unique immune cells that function as sentinels in host defence
reactions, including immediate hypersensitivity responses and allergic responses.
The mast cell-specific receptor named MAS-related G protein-coupled receptor X2
(MRGPRX2) triggers mast-cell degranulation, a key process in anaphylactoid
reactions. It is widely observed that antimicrobials can induce pseudo-allergic
reactions (i.e. IgE-independent mechanism) with symptoms ranging from skin
inflammation to life-threatening systemic anaphylaxis. However, their direct
involvement and the mechanisms underlying anaphylactoid reactions caused by
antimicrobials have not been demonstrated. Structurally different antimicrobials
were screened by Ca2+ imaging using MRGPRX2 overexpressing HEK293 cells. MRGPRX2
related anaphylactoid reactions induced by these components were investigated by
body temperature drop and mast cell degranulation assays. We showed that MRGPRX2
is involved in allergic-like reactions to three types of antimicrobials in a dose
dependent manner. However, mast cells lacking the receptor show reduced
degranulation. Furthermore, mice without MAS-related G protein-coupled receptor
B2 (the orthologous gene of MRGPRX2) exhibited reduced substance-induced
inflammation. Interestingly, beta-lactam and antiviral nucleoside analogues did
not induce anaphylactic reactions, which were also observed in vitro. These
results should alarm many clinicians that such drugs might induce anaphylactoid
reactions and provide guidance on safe dosage of these drugs.
PMID- 28688197
TI - Body size of young adult Polish college-age women born before, during, and after
WWII.
AB - OBJECTIVES: The aim of this study was to compare the young adult body size of
Polish female university students born before, during, and after WWII. METHODS:
Age, height, and weight of 492 students measured between 1956 and 1972 were
accessed from the Department of Anthropology archives (Adam Mickiewicz
University, Poznan). The sample was divided into three birth year cohorts
relative to WWII: before (n = 120), during (n = 196), and after (n = 176). Birth
years spanned 1935 through 1952. BMI was calculated. Body size among birth
cohorts was compared with age of the student and education level of the father as
covariates (ANCOVA). RESULTS: The birth cohorts differed significantly in height
(P < .01), but not in weight and BMI. Women born during WWII were shorter than
women born before and after the war; heights of latter cohorts did not differ.
The trend for weight was similar, but differences were not significant. Birth
cohorts did not differ in BMI. CONCLUSIONS: Young adult heights of women born
during WWII were shorter than the heights of women born before and immediately
after the war, although differences were relatively small.
PMID- 28688198
TI - Study of the interactions between proximal femur 3d bone shape, cartilage health,
and biomechanics in patients with hip Osteoarthritis.
AB - In this study quantitative MRI and gait analysis were used to investigate the
relationships between proximal femur 3D bone shape, cartilage morphology,
cartilage biochemical composition, and joint biomechanics in subject with hip
Osteoarthritis (OA). Eighty subjects underwent unilateral hip MR-imaging: T1rho
and T2 relaxation times were extracted through voxel based relaxometry and bone
shape was assessed with 3D MRI-based statistical shape modeling. In addition, 3D
gait analysis was performed in seventy-six of the studied subjects. Associations
between shape, cartilage lesion presence, severity, and cartilage T1rho and T2
were analyzed with linear regression and statistical parametric mapping. An ad
hoc analysis was performed to investigate biomechanics and shape associations.
Our results showed that subjects with a higher neck shaft angle in the coronal
plane (higher mode 1, coxa valga), thicker femoral neck and a less spherical
femoral head (higher mode 5, pistol grip) exhibited more severe acetabular and
femoral cartilage abnormalities, showing different interactions with demographics
factors. Subjects with coxa valga also demonstrated a prolongation of T1rho and
T2. Subjects with pistol grip deformity exhibited reduced hip internal rotation
angles and subjects with coxa valga exhibited higher peak hip adduction moment
and moment impulse. The results of this study establish a clear relationship
between 3D proximal femur shape variations and markers of hip joint degeneration
morphological, compositional, well as insight on the possible interactions with
demographics and biomechanics, suggesting that 3D MRI-based bone shape maybe a
promising biomarker of early hip joint degeneration. (c) 2017 Orthopaedic
Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:330-341,
2018.
PMID- 28688200
TI - Conflicts of Interest in Emergency Medicine.
AB - Conflicts of interest (COIs) are common in the practice of emergency medicine and
may be present in the areas of clinical practice, relations with industry, expert
witness testimony, medical education, research, and organizations. A COI occurs
when there is dissonance between a primary interest and another interest. The
concept of professionalism in medicine places the patient as the primary interest
in any interaction with a physician. We contend that patient welfare is the
ultimate interest in the entire enterprise of medicine. Recognition and
management of potential, real, and perceived COIs is essential to the ethical
practice of emergency medicine. This paper discusses how to recognize, address,
and manage them.
PMID- 28688199
TI - Differential expression of PARK2 splice isoforms in an in vitro model of
dopaminergic-like neurons exposed to toxic insults mimicking Parkinson's disease.
AB - Mutations in PARK2 (or parkin) are responsible for 50% of cases of autosomal
recessive juvenile-onset Parkinson's disease (PD). To date, 21 alternative splice
variants of the human gene have been cloned. Yet most studies have focused on the
full-length protein, whereas the spectrum of the parkin isoforms expressed in PD
has never been investigated. In this study, the role of parkin proteins in PD
neurodegeneration was explored for the first time by analyzing their expression
profile in an in vitro model of PD. To do so, undifferentiated and all-trans
retinoic-acid (RA)-differentiated SH-SY5Y cells (which thereby acquire a PD-like
phenotype) were exposed to PD-mimicking neurotoxins: 1-methyl-4-phenylpyridinium
(MPP+ ) and 6-hydroxydopamine (6-OHDA) are widely used in PD models, whereas
carbonyl cyanide m-chlorophenyl hydrazone (CCCP) and carbobenzoxy-Leu-Leu
leucinal (MG132) interfere, respectively, with mitochondrial mitophagy and
proteasomal degradation. Following treatment with each neurotoxin H1, the first
parkin isoform to be cloned, was down-regulated compared to the respective
controls both in undifferentiated and RA-differentiated cells. In contrast, the
expression pattern of the minor splice isoforms varied as a function of the
compound used: it was largely unchanged in both cell cultures (eg, H21-H6, H12,
XP isoform) or it showed virtually opposite alterations in undifferentiated and
RA-differentiated cells (eg, H20 and H3 isoform). This complex picture suggests
that up- or down-regulation may be a direct effect of toxin exposure, and that
the different isoforms may exert different actions in neurodegeneration via
modulation of different molecular pathways.
PMID- 28688201
TI - Contrasting patterns of X-chromosome divergence underlie multiple sex-ratio
polymorphisms in stalk-eyed flies.
AB - Sex-linked segregation distorters cause offspring sex ratios to differ from
equality. Theory predicts that such selfish alleles may either go to fixation and
cause extinction, reach a stable polymorphism or initiate an evolutionary arms
race with genetic modifiers. The extent to which a sex ratio distorter follows
any of these trajectories in nature is poorly known. Here, we used X-linked
sequence and simple tandem repeat data for three sympatric species of stalk-eyed
flies (Teleopsis whitei and two cryptic species of T. dalmanni) to infer the
evolution of distorting X chromosomes. By screening large numbers of field and
recently laboratory-bred flies, we found no evidence of males with strongly
female-biased sex ratio phenotypes (SR) in one species but high frequencies of SR
males in the other two species. In the two species with SR males, we find
contrasting patterns of X-chromosome evolution. T. dalmanni-1 shows chromosome
wide differences between sex-ratio (XSR ) and standard (XST ) X chromosomes
consistent with a relatively old sex-ratio haplotype based on evidence including
genetic divergence, an inversion polymorphism and reduced recombination among XSR
chromosomes relative to XST chromosomes. In contrast, we found no evidence of
genetic divergence on the X between males with female-biased and nonbiased sex
ratios in T. whitei. Taken with previous studies that found evidence of genetic
suppression of sex ratio distortion in this clade, our results illustrate that
sex ratio modification in these flies is undergoing recurrent evolution with
diverse genomic consequences.
PMID- 28688203
TI - Assessment of colorectal length using the electromagnetic capsule tracking
system: a comparative validation study in healthy subjects.
AB - AIM: We aimed to determine colorectal length with the 3D-Transit system by
describing a 'centreline' of capsule movement and comparing it with known
anatomy, as determined by magnetic resonance imaging (MRI). Further, we aimed to
test the day-to-day variation of colorectal length assessed with the system.
METHOD: The 3D-Transit system consists of electromagnetic capsules that can be
tracked as they traverse the gastrointestinal tract. Twenty-five healthy subjects
were examined with both 3D-Transit and MRI. Another 21 healthy subjects were
examined with 3D-Transit on two consecutive days. RESULTS: Computation of
colorectal length from capsule passage was possible for 60 of the 67 3D-Transit
recordings. The length of the colorectum measured with MRI and 3D-Transit was 95
(75-153) cm and 99 (77-147) cm, respectively (P = 0.15). The coefficient of
variation (CV) between MRI and 3D-Transit was 7.8%. Apart from the
caecum/ascending colon being 26% (P = 0.002) shorter on MRI, there were no other
differences in total or segmental colorectal lengths between methods (all P >
0.05). The length of the colorectum measured with 3D-Transit on two consecutive
days was 102 (73-119) cm and 103 (75-123) cm (P = 0.67). The CV between days was
7.3%. CONCLUSION: The 3D-Transit system allows accurate and reliable
determination of colorectal length compared with MRI-derived colorectal length
and between days. Antegrade or retrograde capsule movement relative to this
centreline, as well as the length and speed of movements, may be determined by
future studies to allow better classification and treatment in patients with
dysmotility.
PMID- 28688202
TI - Influence of Human Leukocyte Antigen (HLA) Alleles and Killer Cell Immunoglobulin
Like Receptors (KIR) Types on Heparin-Induced Thrombocytopenia (HIT).
AB - Heparin-induced thrombocytopenia (HIT) is an unpredictable, life-threatening,
immune-mediated reaction to heparin. Variation in human leukocyte antigen (HLA)
genes is now used to prevent immune-mediated adverse drug reactions. Combinations
of HLA alleles and killer cell immunoglobulin-like receptors (KIR) are associated
with multiple autoimmune diseases and infections. The objective of this study is
to evaluate the association of HLA alleles and KIR types, alone or in the
presence of different HLA ligands, with HIT. HIT cases and heparin-exposed
controls were identified in BioVU, an electronic health record coupled to a DNA
biobank. HLA sequencing and KIR type imputation using Illumina OMNI-Quad data
were performed. Odds ratios for HLA alleles and KIR types and HLA*KIR
interactions using conditional logistic regressions were determined in the
overall population and by race/ethnicity. Analysis was restricted to KIR types
and HLA alleles with a frequency greater than 0.01. The p values for HLA and KIR
association were corrected by using a false discovery rate q<0.05 and HLA*KIR
interactions were considered significant at p<0.05. Sixty-five HIT cases and 350
matched controls were identified. No statistical differences in baseline
characteristics were observed between cases and controls. The HLA-DRB3*01:01
allele was significantly associated with HIT in the overall population (odds
ratio 2.81 [1.57-5.02], p=2.1*10-4 , q=0.02) and in individuals with European
ancestry, independent of other alleles. No KIR types were associated with HIT,
although a significant interaction was observed between KIR2DS5 and the HLA-C1
KIR binding group (p=0.03). The HLA-DRB3*01:01 allele was identified as a
potential risk factor for HIT. This class II HLA gene and allele represent
biologically plausible candidates for influencing HIT pathogenesis. We found
limited evidence of the role of KIR types in HIT pathogenesis. Replication and
further study of the HLA-DRB3*01:01 association is necessary.
PMID- 28688204
TI - Enhancing expression of the pseudorabies virus glycoprotein E in yeast and its
application in an indirect sandwich ELISA.
AB - AIMS: The purpose of this study was to produce a recombinant pseudorabies virus
(PRV) glycoprotein E (gE) protein with the correct antigenicity for use as a low
cost diagnostic antigen. METHODS AND RESULTS: The gene fragment encoding the
amino-terminal immunodominant region of PRV gE (codons 31-270) (gEN31-270) was
codon optimized and expressed constitutively and secreted using a Pichia pastoris
expression system. Yeast-expressed gEN31-270 (ygEN31-270) was harvested from the
culture supernatant, and ygEN31-270 was shown to exhibit N-linked glycosylation.
An indirect sandwich enzyme-linked immunosorbent assay (ELISA) was developed
using ygEN31-270 as a coating antigen, and the results showed that the assay had
high sensitivity and specificity, as well as almost perfect concordance with a
commercial gE ELISA kit. CONCLUSIONS: The immunodominant region (amino acids 31
270) of gE was expressed successfully in P. pastoris using a codon optimization
strategy. ygEN31-270 was secreted and N-glycosylated. The ygEN31-270-based
indirect sandwich ELISA showed high sensitivity and specificity to detect gE
specific antibodies in swine serum samples. SIGNIFICANCE AND IMPACT OF THE STUDY:
The ygEN31-270-based indirect sandwich ELISA may provide an alternative method
for developing a diagnostic kit with easy manipulation and low cost.
PMID- 28688205
TI - Utilization of Organs From Donors According to Hepatitis C Antibody and Nucleic
Acid Testing Status: Time for Change.
AB - Previous studies have grouped all donors positive for hepatitis C virus (HCV)
antibody (Ab). Only recently has donor HCV nucleic acid testing (NAT) become
routine, and the impact of Ab and NAT status on organ utilization is unknown.
Using the United Network for Organ Sharing database, we identified 9290 donors
from 2015 to 2016 for whom both HCV Ab and NAT data were available and compared
organ utilization by HCV status. Overall, 93.8% of donors were Ab negative and
NAT negative (Ab-NAT-), 0.15% were Ab negative and NAT positive, 1.8% were Ab
positive and NAT negative (Ab+NAT-), and 4.2% were both Ab and NAT positive
(Ab+NAT+). Ab-NAT- donors donated at the highest rate for all organs except
livers, of which Ab+NAT- donors donated at a higher rate (81.2% vs 73.2%, p =
0.03). Livers were discarded for reasons related to abnormal biopsies in Ab+NAT+
donors, whereas kidneys from Ab- or NAT-positive donors were discarded for
reasons related to HCV status. Using a propensity score-matched model, we
estimated that using Ab+NAT- donors at the same rate as Ab-NAT- donors could
result in 48 more kidney donors, 37 more heart donors, and 15 more lung donors
annually. We urge the use of HCV Ab+NAT- donors for appropriately selected and
consenting recipients.
PMID- 28688207
TI - The application of a microfluidic reactor including spontaneously adsorbed
trypsin for rapid protein digestion of human tear samples.
AB - PURPOSE: The application of a newly developed microfluidic immobilized enzymatic
reactor (IMER) designed to accelerate protein digestion in clinical samples is
presented. EXPERIMENTAL DESIGN: The IMER contains trypsin adsorbed on the porous
surface of a PDMS microfluidic chip. Human tear with its relatively low volume
and high protein content is collected and used for testing the digestion
efficiency of the IMER. With the use of CZE peptide mapping, the efficiency and
reproducibility of the reactor are investigated. RESULTS: No significant
difference is observed in the CZE peptide profiles of the same tear sample
digested in-solution or via microfluidic IMER. LC-MS measurements show that the
microfluidic IMER digestion enables the identification of more proteins compared
to standard in-solution digestion and those proteins that are identified with
both digestion methods have higher sequence coverage when digested with the IMER.
CONCLUSIONS AND CLINICAL RELEVANCE: The proposed reactor is well-suited for rapid
and efficient protein digestion and even eight digestions can be carried out
simultaneously. The PDMS chip is inexpensive and easy to fabricate, thus its
application can be an attractive alternative for proteomic related research.
PMID- 28688206
TI - Absence of clinical disease and contact transmission of HPAI H5NX clade 2.3.4.4
from North America in experimentally infected pigs.
AB - BACKGROUND: In the fall of 2014, highly pathogenic avian influenza (HPAI) subtype
H5N8 clade 2.3.4.4 was introduced into North America by migrating waterfowl from
Asia where, through reassortment, novel HPAI H5N2 and H5N1 viruses emerged.
OBJECTIVES: Assess the susceptibility of pigs to HPAI H5N1, H5N2, and H5N8 clade
2.3.3.3 from North America. METHODS: Pigs and trachea explants were inoculated
with a representative panel of H5NX clade 2.3.4.4 HPAI viruses from North
America. Nasal swabs, BALF, and sera were collected to assess replication and
transmission in challenged and direct contact pigs by RRT-PCR, virus isolation,
hemagglutination inhibition, and ELISA. RESULTS: Limited virus replication was
restricted to the lower respiratory tract of challenged pigs, though absent in
the nasal passages and trachea cultures, as determined by RRT-PCR in all samples.
Seroconversion of inoculated pigs was detected by NP ELISA but was not reliably
detected by antigen-specific hemagglutination inhibition. Boost with adjuvanted
virus was required for the production of neutralizing antibodies to assess cross
reactivity between wild-type avian strains. All RRT-PCR and serology tests were
negative for contact animals indicating a failure of transmission from primary
inoculated pigs. CONCLUSIONS: H5NX clade 2.3.4.4 strains can replicate in the
lower respiratory tract of swine upon high titer inoculation, though appear to be
incapable of replication in swine nasal epithelium in vivo or ex vivo in trachea
explants in culture. Infected pigs did not produce high levels of serum
antibodies following infection. Collectively, our data show HPAI H5NX clade
2.3.4.4 viruses to be poorly adapted for replication and transmission in swine.
PMID- 28688208
TI - Human profilin 1 is a negative regulator of CTL mediated cell-killing and
migration.
AB - The actin-binding protein profilin1 (PFN1) plays a central role in actin
dynamics, which is essential for cytotoxic T lymphocyte (CTL) functions. The
functional role of PFN1 in CTLs, however still remains elusive. Here, we identify
PFN1 as the only member of the profilin family expressed in primary human CD8+ T
cells. Using in vitro assays, we find that PFN1 is a negative regulator of CTL
mediated elimination of target cells. Furthermore, PFN1 is involved in activation
induced lytic granule (LG) release, CTL migration and modulation of actin
structures at the immunological synapse (IS). During CTL migration, PFN1
modulates the velocity, protrusion formation patterns and protrusion
sustainability. In contrast, PFN1 does not significantly affect migration
persistence and the rates of protrusion emergence and retraction. Under in vitro
conditions mimicking a tumor microenvironment, we show that PFN1 downregulation
promotes CTL invasion into a 3D matrix, without affecting the viability of CTLs
in a hydrogen peroxide-enriched microenvironment. Highlighting its potential
relevance in cancer, we find that in pancreatic cancer patients, PFN1 expression
is substantially decreased in peripheral CD8+ T cells. Taken together, we
conclude that PFN1 is a negative regulator for CTL-mediated cytotoxicity and may
have an impact on CTL functionality in a tumor-related context.
PMID- 28688209
TI - Quantifying the efficiency of Saccharomyces cerevisiae translocation tags.
AB - Compartmentalization of metabolic pathways into organelles of the yeast
Saccharomyces cerevisiae has been used to improve chemical production. Pathway
compartmentalization aids chemical production by bringing enzymes into close
proximity to one another, placing enzymes near key starting metabolites or
essential co-factors, increasing the effective concentration of metabolic
intermediates, and providing a more suitable chemical environment for enzymatic
activity. Although several translocation tags have been used to localize enzymes
to different yeast organelles, their translocation efficiencies have not been
quantified. Here, we systematically quantify the translocation efficiencies of 10
commonly used S. cerevisiae tags by localizing green fluorescent protein (GFP)
into three yeast organelles: the mitochondrion (4 tags), the vacuole (3 tags),
and the peroxisome (3 tags). Further, we investigate whether plasmid copy number
or mRNA levels vary with tag translocation efficiency. Quantification of the
efficiencies of S. cerevisiae translocation tags provides an important resource
for bioengineering practitioners when choosing a tag to compartmentalize their
desired protein. Finally, these efficiencies can be used to determine the
percentage of enzyme compartmentalization and, thus, help better quantify effects
of compartmentalization on metabolic pathway efficiency.
PMID- 28688210
TI - Infection with influenza A(H1N1)pdm09 during the first wave of the 2009 pandemic:
Evidence from a longitudinal seroepidemiologic study in Dhaka, Bangladesh.
AB - BACKGROUND: We determined influenza A(H1N1)pdm09 antibody levels before and after
the first wave of the pandemic in an urban community in Dhaka, Bangladesh.
METHODS: We identified a cohort of households by stratified random sampling. We
collected baseline serum specimens during July-August 2009, just prior to the
initial wave of the 2009 pandemic in this community and a second specimen during
November 2009, after the pandemic peak. Paired sera were tested for antibodies
against A(H1N1)pdm09 virus using microneutralization assay and hemagglutinin
inhibition (HI) assay. A fourfold increase in antibody titer by either assay with
a titer of >=40 in the convalescent sera was considered a seroconversion. At
baseline, an HI titer of >=40 was considered seropositive. We collected
information on clinical illness from weekly home visits. RESULTS: We tested 779
paired sera from the participants. At baseline, before the pandemic wave, 1%
overall and 3% of persons >60 years old were seropositive. After the first wave
of the pandemic, 211 (27%) individuals seroconverted against A(H1N1)pdm09.
Children aged 5-17 years had the highest proportion (37%) of seroconversion.
Among 264 (34%) persons with information on clinical illness, 191 (72%) had
illness >3 weeks prior to collection of the follow-up sera and 73 (38%)
seroconverted. Sixteen (22%) of these 73 seroconverted participants reported no
clinical illness. CONCLUSION: After the first pandemic wave in Dhaka, one in four
persons were infected by A(H1N1)pdm09 virus and the highest burden of infection
was among the school-aged children. Seroprevalence studies supplement traditional
surveillance systems to estimate infection burden.
PMID- 28688211
TI - Reducing sedation time for thyroplasty with arytenoid adduction with sequential
anesthetic technique.
AB - OBJECTIVE: To determine the extent to which a sequential anesthetic technique 1)
shortens time under sedation for thyroplasty with arytenoid adduction (TP-AA), 2)
affects the total operative time, and 3) changes the voice outcome compared to TP
AA performed entirely under sedation/analgesia. STUDY DESIGN: Case-control study.
METHODS: A new sequential anesthetic technique of performing most of the TP-AA
surgery under general anesthesia (GA), followed by transition to
sedation/analgesia (SA) for voice assessment, was developed to achieve smooth
emergence from GA. Twenty-five TP-AA cases performed with the sequential GA-SA
technique were compared with 25 TP-AA controls performed completely under
sedation/analgesia. The primary outcome measure was the time under sedation.
Voice improvement, as assessed by Consensus Auditory-Perceptual Evaluation of
Voice, and total operative time were secondary outcome measures. RESULTS: With
the conventional all-SA anesthetic, the duration of SA was 209 +/- 26.3 minutes.
With the sequential GA-SA technique, the duration of SA was 79.0 +/- 18.9
minutes, a 62.3% reduction (P < 0.0001). There was no significant difference in
the total operative time (209.5 vs. 200.9 minutes; P = 0.42) or in voice outcome.
This sequential anesthetic technique has been easily adopted by multiple
anesthesiologists and nurse anesthetists at our institution. CONCLUSION: TP-AA is
effectively performed under sequential GA-SA technique with a significant
reduction in the duration of time under sedation. This allows the surgeon to
perform the technically more challenging part of the surgery under GA, without
having to contend with variability in patient tolerance for laryngeal
manipulation under sedation. LEVEL OF EVIDENCE: 3b. Laryngoscope, 127:2813-2817,
2017.
PMID- 28688212
TI - Treatment disparities in the management of epistaxis in United States emergency
departments.
AB - OBJECTIVES: There is limited data on epistaxis presentation and management
patterns in U.S. emergency departments (EDs). We aim to characterize patients who
present to the ED with epistaxis and identify factors associated with nasal
packing use. STUDY DESIGN: Retrospective review of Nationwide Emergency
Department Sample (NEDS) from 2009 to 2011. METHODS: NEDS was queried for patient
visits with a primary diagnosis of epistaxis (International Classification of
Diseases, Ninth Revision, Clinical Modification code 784.7). Patient
demographics, comorbidities, and hospital characteristics were obtained.
Predictors of nasal packing were determined by multivariable logistic regression.
RESULTS: There were 1,234,267 ED visits for epistaxis. The highest proportion of
patients were seen in the winter (37.2%) at nontrauma hospitals (76.9%), and were
discharged home (95.5%). Fifteen percent of patients were on long-term
anticoagulation, 33% had hypertension, and 0.9% had a coagulopathy. Nasal packing
was utilized in 243,268 patients (19.7%). Predictors strongly associated with
nasal packing included lower socioeconomic quartile (odds ratio [OR] 1.30, 95%
confidence interval [CI] = 1.10-1.53), hospital located in the geographic South
(OR 1.62, CI = 1.12-2.34) and Midwest (OR 1.85, P < 0.0001), and nontrauma
hospital (OR 1.56, CI = 1.19-2.05). Other factors included long-term
anticoagulation (OR 1.21, CI = 1.10-1.33), winter season (OR 1.20, CI = 1.12
1.23), male gender (OR 1.14, CI = 1.10-1.17), and older age (OR 1.01, CI = 1.01
1.02). Mean ED charge was greater for patients who were packed ($1,473 vs.
$1,048, P < 0.0001). CONCLUSION: Several factors, including lower socioeconomic
status, geographic location, and nontrauma hospital designation, predict use of
nasal packing. These results raise concerns about potential treatment disparities
that may result in increased patient morbidity and costs. LEVEL OF EVIDENCE: 2C.
Laryngoscope, 128:356-362, 2018.
PMID- 28688213
TI - Multivalent methionine-functionalized biocompatible block copolymers for targeted
small interfering RNA delivery and subsequent reversal effect on adriamycin
resistance in human breast cancer cell line MCF-7/ADR.
AB - BACKGROUND: Cationic polymers are outstanding representatives of the most
efficient small interfering RNA (siRNA) vectors. Low cytotoxicity and siRNA
protecting effect can be obtained with these cationic polymers via a variety of
structural modifications. Nevertheless, the gap between their efficiency and the
requirement for therapeutic processes is still noticeable. METHODS: A cationic
polymer vector was synthesized via the copolymerization of N-(1,3-dihydroxy
propan-2-yl)methacrylamide (DHPMA) and N-(3-aminopropyl)methacrylamide (APMA).
RESULTS: APMA provides amine functionality that allows the conjugation of
guanidine and methionine groups. Attributed to the hydroxy groups of DHPMA, the
synthesized guanidine and methionine grafted DHPMA-b-APMA block copolymer (mDG)
is water soluble and has good biocompatibility. The obtained mDG has high zeta
potential, narrow molecular weight distribution, better membrane-penetrating
ability, high transfection efficiency, tumor cell targeting ability and high
stability. CONCLUSIONS: The synthesized polymer vector can deliver siRNA
molecules into tumor cells and then reverse drug resistance by down regulation of
P-glycoprotein mRNA expression.
PMID- 28688214
TI - Uterine molecular changes for non-invasive embryonic attachment in the marsupials
Macropus eugenii (Macropodidae) and Trichosurus vulpecula (Phalangeridae).
AB - Pregnancy in mammals requires remodeling of the uterus to become receptive to the
implanting embryo. Remarkably similar morphological changes to the uterine
epithelium occur in both eutherian and marsupial mammals, irrespective of
placental type. Nevertheless, molecular differences in uterine remodeling
indicate that the marsupial uterus employs maternal defences, including molecular
reinforcement of the uterine epithelium, to regulate embryonic invasion. Non
invasive (epitheliochorial) embryonic attachment in marsupials likely evolved
secondarily from invasive attachment, so uterine defences in these species may
prevent embryonic invasion. We tested this hypothesis by identifying localization
patterns of Talin, a key basal anchoring molecule, in the uterine epithelium
during pregnancy in the tammar wallaby (Macropus eugenii; Macropodidae) and the
brush tail possum (Trichosurus vulpecula; Phalangeridae). Embryonic attachment is
non-invasive in both species, yet Talin undergoes a clear distributional change
during pregnancy in M. eugenii, including recruitment to the base of the uterine
epithelium just before attachment, that closely resembles that of invasive
implantation in the marsupial species Sminthopsis crassicaudata. Basal
localization occurs throughout pregnancy in T. vulpecula, although, as for M.
eugenii, this pattern is most specific prior to attachment. Such molecular
reinforcement of the uterine epithelium for non-invasive embryonic attachment in
marsupials supports the hypothesis that less-invasive and non-invasive embryonic
attachment in marsupials may have evolved via accrual of maternal defences.
Recruitment of basal molecules, including Talin, to the uterine epithelium may
have played a key role in this transition.
PMID- 28688215
TI - Alterations in structural macromolecules and chondrocyte deformations in lapine
retropatellar cartilage 9 weeks after anterior cruciate ligament transection.
AB - The structural integrity and mechanical environment of the articular cartilage
matrix directly affect chondrocyte deformations. Rabbit models of early
osteoarthritis at 9 weeks following anterior cruciate ligament transection (ACLT)
have been shown to alter the deformation behavior of superficial zone
chondrocytes in mechanically loaded articular cartilage. However, it is not fully
understood whether these changes in cell mechanics are caused by changes in
structural macromolecules in the extracellular matrix. Therefore, the purpose of
this study was to characterize the proteoglycan content, collagen content, and
collagen orientation at 9 weeks post ACLT using microscopic techniques, and
relate these changes to the altered cell mechanics observed upon mechanical
loading of cartilage. At 9 weeks following ACLT, collagen orientation was
significantly (p < 0.05) altered and proteoglycan content was significantly (p <
0.05) reduced in the superficial zone cartilage matrix. These structural changes
either in the extracellular or pericellular matrix (ECM and PCM) were also
correlated significantly (p < 0.05) with chondrocyte width and height changes,
thereby suggesting that chondrocyte deformation response to mechanical
compression in early OA changes primarily because of alterations in matrix
structure. However, compared to the normal group, proteoglycan content in the PCM
from the ACLT group decreased less than that in the surrounding ECM. Therefore,
PCM could play a key role to protect excessive chondrocyte deformations in the
ACLT group. (c) 2017 Orthopaedic Research Society. Published by Wiley
Periodicals, Inc. J Orthop Res 36:342-350, 2018.
PMID- 28688216
TI - Molecular aspects of diabetes mellitus: Resistin, microRNA, and exosome.
AB - Diabetes mellitus (DM) is known as one of important common endocrine disorders
which could due to deregulation of a variety of cellular and molecular pathways.
A large numbers studies indicated that various pathogenesis events including
mutation, serin phosphorylation, and increasing/decreasing expression of many
genes could contribute to initiation and progression of DM. Insulin resistance is
one of important factors which could play critical roles in DM pathogenesis. It
has been showed that insulin resistance via targeting a sequence of cellular and
molecular pathways (eg, PI3 kinases, PPARgamma co-activator-1, microRNAs,
serine/threonine kinase Akt, and serin phosphorylation) could induce DM. Among of
various factors involved in DM pathogenesis, microRNAs, and exosomes have been
emerged as effective factors in initiation and progression of DM. A variety of
studies indicated that deregulation of these molecules could change behavior of
various types of cells and contribute to progression of DM. Resistin is other
main factor which is known as signal molecule involved in insulin resistance.
Multiple lines evidence indicated that resistin exerts its effects via affecting
on glucose metabolism, inhibition of fatty acid uptake and metabolism with
affecting on a variety of targets such as CD36, fatty acid transport protein 1,
Acetyl-CoA carboxylase, and AMP-activated protein kinase. Here, we summarized
various molecular aspects are associated with DM particularly the molecular
pathways involved in insulin resistance and resistin in DM. Moreover, we
highlighted exosomes and microRNAs as effective players in initiation and
progression of DM.
PMID- 28688218
TI - Early versus late inpatient awake transcervical injection laryngoplasty after
thoracic aortic repair.
AB - BACKGROUND: Vocal fold movement impairment (VFMI), a known complication following
thoracic aortic surgery, has been associated with poorer surgical outcomes,
including higher pulmonary complications and longer length of stay (LOS). Awake
transcervical injection laryngoplasty in the inpatient setting serves to augment
pulmonary toilet function for affected patients. This study investigates clinical
outcomes of patients who underwent early versus late injection laryngoplasty
following aortic surgery. METHODS: A 5-year review (2011-2016) of 35 patients who
underwent inpatient injection laryngoplasty for VFMI following aortic repair was
conducted. Data included demographics, surgery parameters, laryngologic
evaluation, pulmonary complications, LOS, and mortality. Early injection was
defined as within 5 days from extubation. Statistical analyses were performed
using SPSS, version 17.0 (IBM Corp., Armonk, NY). RESULTS: All 35 patients (mean
age 56, 77% male) underwent left vocal-fold injection laryngoplasty without
complication. There were 15 (43%) early procedures and 20 (57%) late procedures.
Mean LOS for early and late injection groups (13 vs. 20 days, respectively)
significantly differed (P = 0.04, 95% confidence interval (CI) 0.3 to 14.4).
Early laryngoplasty cohorts experienced less pulmonary complications (20%) than
those who had late medialization (50%), but this did not reach significance (P =
0.06, 95% CI -0.3 to 8.1). The most common complication type in both groups was
therapeutic bronchoscopy. CONCLUSION: Early awake injection laryngoplasty within
5 days from extubation is feasible and may improve clinical outcomes for patients
with VFMI following aortic repair. Further prospective studies on this approach
for VFMI after thoracic surgery are needed. LEVEL OF EVIDENCE: 4. Laryngoscope,
128:144-147, 2018.
PMID- 28688217
TI - Yes-associated protein 1 promotes the differentiation and mineralization of
cementoblast.
AB - Yes-associated protein 1 (YAP1) transcriptional coactivator is a mediator of
mechanosensitive signaling. Cementum, which covers the tooth root surface,
continuously senses external mechanical stimulation. Cementoblasts are
responsible for the mineralization and maturation of the cementum. However, the
effect of YAP1 on cementoblast differentiation remains largely unknown. In this
study, we initially demonstrated that YAP1 overexpression enhanced the
mineralization ability of cementoblasts. YAP1 upregulated the mRNA and protein
expression of several cementogenesis markers, such as alkaline phosphatase (ALP),
runt-related transcription factor 2 (Runx2), osteocalcin (OCN), and dentin matrix
acidic phosphoprotein 1 (DMP1). The YAP1 overexpression group showed higher
intensities of ALP and Alizarin red stain than the YAP1-knockdown group.
Unexpectedly, a sharp increase in the expression of dentin sialophosphoprotein
(DSPP) was induced by the overexpression of YAP1. Knockdown of YAP1 suppressed
DSPP transcriptional activity. YAP1 overexpression activated Smad-dependent BMP
signaling and slightly inhibited Erk1/2 signaling pathway activity. Treatment
with specific BMP antagonist (LDN193189) prevented the upregulation of the mRNA
levels of ALP, RUNX2, and OCN, as well as intensity of ALP-stained and
mineralized nodules in cementoblasts. The Erk1/2 signaling pathway inhibitor (PD
98,059) upregulated these cementogenesis markers. Thus, our study suggested that
YAP1 enhanced cementoblast mineralization in vitro. YAP1 exerted its effect on
the cementoblast partly by regulating the Smad-dependent BMP and Erk1/2 signaling
pathways.
PMID- 28688219
TI - Performance of a cost-effective and automated blood counting system for resource
limited settings operated by trained and untrained users.
AB - Current flow-based blood counting devices require expensive and centralized
medical infrastructure and are not appropriate for field use. In this article we
report a streamlined, easy-to-use method to count red blood cells (RBC), white
blood cells (WBC), platelets (PLT) and 3-part WBC differential through a cost
effective and automated image-based blood counting system. The approach consists
of using a compact, custom-built microscope with large field-of-view to record
bright-field and fluorescence images of samples that are diluted with a single,
stable reagent mixture and counted using automatic algorithms. Sample collection
utilizes volume-controlled capillary tubes, which are then dropped into a
premixed, shelf-stable solution to stain and dilute in a single step. Sample
measurement and analysis are fully automated, requiring no input from the user.
Cost of the system is minimized through the use of custom-designed motorized
components. We compare the performance of our system, as operated by trained and
untrained users, to the clinical gold standard on 120 adult blood samples,
demonstrating agreement within Clinical Laboratory Improvement Amendments
guidelines, with no statistical difference in performance among different
operator groups. The system's cost-effectiveness, automation and performance
indicate that it can be successfully translated for use in low-resource settings
where central hematology laboratories are not accessible.
PMID- 28688220
TI - Assessment of the protein interaction between coagulation factor XII and corn
trypsin inhibitor by molecular docking and biochemical validation.
AB - : Essentials Corn Trypsin Inhibitor (CTI) is a selective inhibitor of coagulation
Factor XII (FXII). Molecular modelling of the CTI-FXIIa complex suggested a
canonical inhibitor binding mode. Mutagenesis revealed the CTI inhibitory loop
and helices alpha1 and alpha2 mediate the interaction. This confirms that CTI
inhibits FXII in canonical fashion and validates the molecular model. SUMMARY:
Background Corn trypsin inhibitor (CTI) has selectivity for the serine proteases
coagulation factor XII and trypsin. CTI is in widespread use as a reagent that
specifically inhibits the intrinsic pathway of blood coagulation but not the
extrinsic pathway. Objectives To investigate the molecular basis of FXII
inhibition by CTI. Methods We performed molecular docking of CTI, using its known
crystal structure, with a model of the activated FXII (FXIIa) protease domain.
The interaction model was verified by use of a panel of recombinant CTI variants
tested for their ability to inhibit FXIIa enzymatic activity in a substrate
cleavage assay. Results The docking predicted that: (i) the CTI central
inhibitory loop P1 Arg34 side chain forms a salt bridge with the FXIIa S1 pocket
Asp189 side chain; (ii) Trp22 from CTI helix alpha1 interacts with the FXIIa S3
pocket; and (iii) Arg43 from CTI helix alpha2 forms a salt bridge with FXIIa H1
pocket Asp60A. CTI amino acid substitution R34A negated all inhibitory activity,
whereas the G32W, L35A, W22A and R42A/R43A substitutions reduced activity by
large degrees of 108-fold, 41-fold, 158-fold, and 100-fold, respectively; the
R27A, W37A, W39A and R42A substitutions had no effect. Synthetic peptides
spanning CTI residues 20-44 had inhibitory activity that was three-fold to 4000
fold less than that of full-length CTI. Conclusions The data confirm the validity
of a canonical model of the FXIIa-CTI interaction, with helix alpha1 (Trp22),
central inhibitory loop (Arg34) and helix alpha2 (Arg43) of CTI being required
for effective binding by contacting the S1, S3 and H1 pockets of FXIIa,
respectively.
PMID- 28688222
TI - Assembly pathway of a bacterial complex iron sulfur molybdoenzyme.
AB - Protein folding and assembly into macromolecule complexes within the living cell
are complex processes requiring intimate coordination. The biogenesis of complex
iron sulfur molybdoenzymes (CISM) requires use of a system specific chaperone - a
redox enzyme maturation protein (REMP) - to help mediate final folding and
assembly. The CISM dimethyl sulfoxide (DMSO) reductase is a bacterial
oxidoreductase that utilizes DMSO as a final electron acceptor for anaerobic
respiration. The REMP DmsD strongly interacts with DMSO reductase to facilitate
folding, cofactor-insertion, subunit assembly and targeting of the multi-subunit
enzyme prior to membrane translocation and final assembly and maturation into a
bioenergetic catalytic unit. In this article, we discuss the biogenesis of DMSO
reductase as an example of the participant network for bacterial CISM maturation
pathways.
PMID- 28688221
TI - Minimal factor XIII activity level to prevent major spontaneous bleeds.
AB - : Essentials A strong association between bleeding severity and FXIII activity
level (FXIII:C) was shown. The range 5-30 IU dL-1 of FXIII:C was associated with
a high variability of bleeding severity. The PROspective study confirmed the
association between FXIII:C activity and bleeding severity. A FXIII: C of 15 IU
dL-1 is a proposed target to start prophylaxis for prevention of major bleeding.
SUMMARY: Background Congenital factor XIII (FXIII) deficiency is a rare bleeding
disorder associated with significant bleeding manifestations. The European
Network of Rare Bleeding Disorders (EN-RBD) study, performed from 2007 to 2010,
showed a strong association between bleeding severity and FXIII activity in
plasma of patients with FXIII deficiency. Among these patients, variable levels
of FXIII activity, from undetectable to 30%, were associated with a wide range of
bleeding severity. Objectives and patients The present cross-sectional study, in
the frame of the PRO-RBDD project, a prospective cohort study, analyzed data of
64 patients with FXIII deficiency and different types of clinical and laboratory
severity. Results The results of this analysis confirmed that FXIII coagulant
activity in plasma is well associated with clinical severity of patients. In
addition, 15 IU dL-1 of FXIII activity was identified to be the level under which
the probability of spontaneous major bleeding sharply increases (from 50% for
levels of 15 IU dL-1 to more than 90% for levels of 5 IU dL-1 or lower).
Conclusion The PRO-RBDD study suggests a FXIII coagulant activity level of 15 IU
dL-1 as a target to start prophylaxis in order to prevent major bleedings, such
as central nervous system or gastrointestinal tract hemorrhages.
PMID- 28688223
TI - Processing-independent proANP measurement for low concentrations in plasma:
reference intervals and effect of body mass index and plasma glucose.
AB - BACKGROUND: Decreased concentrations of pro-atrial-derived natriuretic peptides
(proABP) in plasma have been associated with obesity and suggested as a predictor
of type 2 diabetes. However, assays for measuring proANP are generally aimed to
quantitate higher concentrations of proANP associated with cardiac disease.
Therefore, we aimed to measure plasma proANP concentrations in a non-obese
Scandinavian reference material and evaluate potential associations of plasma
proANP with body mass index (BMI) and plasma glucose, respectively. METHODS: We
report an optimized processing-independent assay (PIA) for proANP in the lower
concentration range. The assay was optimized by raising the amount of radioactive
tracer and modifying the mixing ratio of resuspended plasma and buffer. Blood
samples from a Scandinavian plasma cohort of 693 healthy subjects were then
analyzed and age and gender-specific reference intervals were determined.
RESULTS: Simple linear regression analyses of proANP and both BMI and plasma
glucose in fasting subjects displayed insignificant associations. Multiple
regression analyses supported these findings. However, a higher median plasma
concentration of proANP was noted among women <50 years compared to men, whereas
no gender-specific differences were seen in other age groups. CONCLUSIONS: Our
results show that in a healthy non-obese population, BMI and plasma glucose in
fasting subjects do not affect plasma proANP concentrations. Our method should be
considered for future studies on low proANP concentration studies, e.g. in
obesity and diabetes.
PMID- 28688224
TI - Defining a roadmap for harmonizing quality indicators in Laboratory Medicine: a
consensus statement on behalf of the IFCC Working Group "Laboratory Error and
Patient Safety" and EFLM Task and Finish Group "Performance specifications for
the extra-analytical phases".
AB - The improving quality of laboratory testing requires a deep understanding of the
many vulnerable steps involved in the total examination process (TEP), along with
the identification of a hierarchy of risks and challenges that need to be
addressed. From this perspective, the Working Group "Laboratory Errors and
Patient Safety" (WG-LEPS) of International Federation of Clinical Chemistry and
Laboratory Medicine (IFCC) is focusing its activity on implementation of an
efficient tool for obtaining meaningful information on the risk of errors
developing throughout the TEP, and for establishing reliable information about
error frequencies and their distribution. More recently, the European Federation
of Clinical Chemistry and Laboratory Medicine (EFLM) has created the Task and
Finish Group "Performance specifications for the extra-analytical phases" (TFG
PSEP) for defining performance specifications for extra-analytical phases. Both
the IFCC and EFLM groups are working to provide laboratories with a system to
evaluate their performances and recognize the critical aspects where improvement
actions are needed. A Consensus Conference was organized in Padova, Italy, in
2016 in order to bring together all the experts and interested parties to achieve
a consensus for effective harmonization of quality indicators (QIs). A general
agreement was achieved and the main outcomes have been the release of a new
version of model of quality indicators (MQI), the approval of a criterion for
establishing performance specifications and the definition of the type of
information that should be provided within the report to the clinical
laboratories participating to the QIs project.
PMID- 28688225
TI - Rivaroxaban non-responders: do plasma measurements have a place?
PMID- 28688226
TI - Towards Multiple Kernel Principal Component Analysis for Integrative Analysis of
Tumor Samples.
AB - Personalized treatment of patients based on tissue-specific cancer subtypes has
strongly increased the efficacy of the chosen therapies. Even though the amount
of data measured for cancer patients has increased over the last years, most
cancer subtypes are still diagnosed based on individual data sources (e.g. gene
expression data). We propose an unsupervised data integration method based on
kernel principal component analysis. Principal component analysis is one of the
most widely used techniques in data analysis. Unfortunately, the straightforward
multiple kernel extension of this method leads to the use of only one of the
input matrices, which does not fit the goal of gaining information from all data
sources. Therefore, we present a scoring function to determine the impact of each
input matrix. The approach enables visualizing the integrated data and subsequent
clustering for cancer subtype identification. Due to the nature of the method, no
hyperparameters have to be set. We apply the methodology to five different cancer
data sets and demonstrate its advantages in terms of results and usability.
PMID- 28688228
TI - Mast cells in neuropathic pain: an increasing spectrum of their involvement in
pathophysiology.
AB - Mast cells are immunological cells that are diversely distributed in different
parts of the body. Their role in various pathological conditions such as
hypersensitivity, atherosclerosis, pulmonary hypertension, and male infertility
has been reported by different scientists. Apart from these, a number of studies
have shown their important role in pathogenesis of neuropathic pain of diverse
aetiology. They have been found to release active mediators, primarily histamine
and serotonin on degranulation in response to different stimuli including
chemical, nerve damage, toxin or disease-related conditions. The mast cells
stabilizer has shown pain attenuating effects by preventing degranulation of mast
cells. Similarly, compound 48/80 (first dose 200 MUg/100 g and after 6-h
interval, second dose of 500 MUg/100 g) caused the degranulation of the
accumulated endoneurial histamine and 5-HT antagonists have shown pain relieving
effects by attenuating the effects of histamine and serotonin, respectively. On
the other hand, the mast cell degranulator compound 48/80 has shown dual action
depending on its time of administration. The present review discusses the
critical role of mast cells in the generation and maintenance of neuropathic pain
in experimental models.
PMID- 28688227
TI - Impact factors on cervical dilation rates in the first stage of labor.
AB - AIMS: To assess cervical dilation rates of nulliparous and multiparous women in
the active first stage of labor and to evaluate significant impact factors.
METHODS: In a retrospective cohort study between January 2007 and July 2014 at
the University Hospital of Zurich in Switzerland, we analyzed 8378 women with
singleton pregnancies in vertex presentation with a vaginal delivery at 34+0 to
42+5 gestational weeks. Median cervical dilation rates were calculated and
different impact factors evaluated. RESULTS: Cervical dilation rates increase
during labor progress with faster rates in multiparous compared with nulliparous
women (P<0.001). Dilation rates exceed 1 cm/h at a dilatation of 6-7 cm, but are
very individual. Accelerating impact factors are multiparity, a greater amount of
cervical dilation and fetal occipitoanterior position, whereas the use of
epidural anesthesia, a higher fetal weight and head circumference decelerate
dilation (P<0.001). CONCLUSION: Cervical dilation is a hyperbolic increasing
process, with faster dilation rates in multiparous compared to nulliparous women
and a reversal point of labor around 6-7 cm, respectively. Besides, cervical
dilation is highly individual and affected by several impact factors. The
diagnosis of labor arrest or prolonged labor should therefore be based on such
rates and on the individual evaluation of every woman.
PMID- 28688232
TI - Aberrant Promoter Methylation of PCDH17 (Protocadherin 17) in Serum and its
Clinical Significance in Renal Cell Carcinoma.
AB - BACKGROUND Current studies indicated that PCDH17 functions as a tumor suppressor,
which is frequently inactivated by aberrant promoter methylation in urologic
tumors. The main purpose of this study was to investigate the methylation status
of PCDH17 in serum and its clinical significance in renal cell carcinoma (RCC).
MATERIAL AND METHODS The methylation status of PCDH17 in serum samples of 142 RCC
patients and 34 controls was evaluated by methylation-specific PCR (MSP). Then we
correlated PCDH17 methylation status with the clinicopathologic features of RCC
patients and patient outcomes. RESULTS We found that PCDH17 was more frequently
methylated in RCC patients than in controls. Moreover, PCDH17 methylation in
serum was significantly correlated with advanced stage (p=0.044), higher grade
(p=0.019), lymph node metastasis (p=0.008) and tumor progression (p<0.001). In
addition, patients with methylated PCDH17 had shorter progression-free survival
(p<0.001) and overall survival (p=0.017) than patients without, and PCDH17
methylation in serum was an independent prognostic factor for worse progression
free survival (HR: 4.215, 95% CI: 1.376-9.032, p<0.001) and overall survival (HR:
5.092, 95% CI: 1.149-12.357, p=0.046) of patients with RCC. CONCLUSIONS The
present study indicates that PCDH17 methylation in serum is a frequent event in
RCC and associated with risk factors of poor outcomes. Moreover, PCDH17
methylation in serum is a potential prognostic biomarker for patients with RCC
after surgery.
PMID- 28688233
TI - Dinitramidoborates: A Fascinating Case of Competing Oxygen and Nitrogen Donors
and Tautomerism.
AB - Reactions of the BH4- anion with equimolar amounts of HN(NO2 )2 or of BH3 ?THF
with K[N(NO2 )2 ]- produced a mono-substituted [BH3 N(NO2 )2 ]- anion, which
contains a B-N connected dinitramido ligand. The reaction of BH4- with two
equivalents of HN(NO2 )2 afforded the di-substituted borate anion consisting of
two isomers, one with both nitramido ligands attached to B through N and the
other one with one ligand attached through N and the other one through O. The
disubstituted dinitramidoborates are marginally stable under ambient conditions,
and the isomer with two N-connected ligands was characterized by its crystal
structure. A tri-substituted borate was tentatively identified by NMR in the
reaction of BH4- with a large excess of HN(NO2 )2 . All of the anions are highly
energetic. Theoretical calculations show that the energy differences between the
B-N and B-O tautomers are small, explaining the formation of both.
PMID- 28688234
TI - Separation and characterization of unknown impurities in cefonicid sodium by trap
free two-dimensional liquid chromatography combined with ion trap time-of-flight
mass spectrometry.
AB - RATIONALE: Seven unknown antibiotic impurities in cefonicid sodium were separated
and characterized by a trap-free two-dimensional liquid chromatography coupled to
high-resolution ion-trap time-of-flight mass spectrometry (2D-LC/IT-TOF MS) using
both positive and negative modes of electrospray ionization. Trap-free 2D-LC and
an online demineralization technique made it possible to characterize cefonicid
sodium under the conditions of the official standard, and the TIC chromatogram
obtained by LC/MS was in conformity with the LC chromatogram obtained by the
official analytical method in the peak sequence of impurities. METHODS: In the
first dimension, the column was a GRACE Alltima C18 (250 mm * 4.6 mm, 5 MUm), and
the gradient elution used 0.02 mol.L-1 ammonium dihydrogen phosphate solution and
methanol as mobile phase. In the second dimension, the analytical column was a
Shimadzu Shim-pack GISS C18 (50 mm * 2.1 mm, 1.9 MUm) with 10 mmol.L-1 ammonium
formate solution and methanol as mobile phase. Full scan LC/MS was first executed
to obtain the exact m/z values of the molecules. Then LC/MS2 and LC-MS3
experiments were performed on the compounds of interest. RESULTS: The structures
of seven unknown degradation products in cefonicid sodium were deduced based on
the high-resolution MSn data using both positive and negative mode. CONCLUSIONS:
The problem of incompatibility between the non-volatile salt mobile phase and
mass spectrometry was solved completely by multidimensional heart-cutting
approaches and an online demineralization technique, which is worthy of
widespread use and application for the advantages of stability and repeatability.
PMID- 28688236
TI - Antigen-specific regulatory T cells: are police CARs the answer?
AB - Cellular therapy with T-regulatory cells (Tregs) is a promising strategy to
control immune responses and restore immune tolerance in a variety of immune
mediated diseases, such as transplant rejection and autoimmunity. Multiple
clinical trials are currently testing this approach, typically by infusing a
single dose of polyclonal Tregs that have been expanded in vitro. However,
evidence from animal models of Treg therapy has clearly shown that antigen
specific Tregs are vastly superior to polyclonal cells, meaning that fewer cells
are needed for the desired therapeutic effect. Traditional methods to obtain
antigen-specific Tregs include antigen-stimulated expansion or T-cell receptor
(TCR) overexpression. However, these methods are limited by low cell numbers,
complex manufacturing procedures, and knowledge of patient-specific TCRs which
recognize disease-relevant MHC-peptide complexes. Recently, several groups have
explored the potential to use chimeric antigen receptors (CARs) to generate
antigen-specific Tregs. Here, we discuss the progress in this field and highlight
the major outstanding questions that remain to be addressed as this approach
moves toward clinical applications.
PMID- 28688235
TI - HIV-Associated Cardiovascular Disease: Role of Connexin 43.
AB - Chronic HIV infection due to effective antiretroviral treatment has resulted in a
broad range of clinical complications, including accelerated heart disease.
Individuals with HIV infection have a 1.5 to 2 times higher incidence of
cardiovascular diseases than their uninfected counterparts; however, the
underlying mechanisms are poorly understood. To explore the link between HIV
infection and cardiovascular diseases, we used postmortem human heart tissues
obtained from HIV-infected and control uninfected individuals to examine connexin
43 (Cx43) expression and distribution and HIV-associated inflammation. Here, we
demonstrate that Cx43 is dysregulated in the hearts of HIV-infected individuals.
In all HIV heart samples analyzed, there were areas where Cx43 was overexpressed
and found along the lateral membrane of the cardiomyocyte and in the intercalated
disks. Areas of HIV tissue with anomalous Cx43 expression and localization also
showed calcium overload, sarcofilamental atrophy, and accumulation of collagen.
All these changes were independent of viral replication, CD4 counts,
inflammation, and type of antiretroviral treatment. Overall, we propose that HIV
infection increases Cx43 expression in heart, resulting in tissue damage that
likely contributes to the high rates of cardiovascular disease in HIV-infected
individuals.
PMID- 28688237
TI - Antibacterial drug development program successes and failures: a pharmacometric
explanation.
AB - My thesis is a simple one. We have not been doing a good enough job selecting
dose regimens for serious infections during the drug development process. If we
are to do a better job in the future, we need to revisit some uncomfortable
places. That is, some notable program failures. To be clear, we are not
revisiting program failures to make anyone uncomfortable or cast aspersions - but
rather so that we sow the seeds for a better future. To that end, we will examine
program failures and successes through a pharmacometric lens. Through this
powerful lens, we will come to understand that many of our failures were not only
predictable, but perhaps expected and entirely avoidable. The goal of this
communication is to set forth the type of thinking and data that is necessary for
rational dose selection.
PMID- 28688238
TI - Increased healthcare facility use in veterans surviving sepsis hospitalization.
AB - PURPOSE: We sought to measure inpatient healthcare utilization among U.S. Veteran
Affairs beneficiaries surviving sepsis hospitalization, and to examine how post
sepsis utilization varies by select patient characteristics. MATERIALS AND
METHODS: Retrospective cohort study of 26,561 Veterans who survived sepsis
hospitalization in 2009. Using difference-in-differences analysis, we compared
changes in healthcare utilization in one year before and one year after sepsis
hospitalization by Veteran age, illness severity, and recent nursing facility
use. RESULTS: Median days in a healthcare facility increased from 5 to 10.
Veterans with recent nursing facility use spent a median 65days (or 86% of days
alive) in a healthcare facility in the year after sepsis. Older age, greater
illness severity, and recent nursing home use were each associated with spending
more days, and a greater proportion of days alive, in a healthcare facility
during the year after sepsis. However, none of these characteristics was
associated with a greater rise in utilization after sepsis. CONCLUSIONS: Veterans
surviving sepsis experience high rates of post-sepsis mortality and significant
increases in healthcare facility use. Recent nursing facility use is strongly
predictive of greater post-sepsis healthcare utilization.
PMID- 28688240
TI - Magnesium status and magnesium therapy in cardiac surgery: A systematic review
and meta-analysis focusing on arrhythmia prevention.
AB - PURPOSE: To investigate magnesium as prophylaxis or treatment of postoperative
arrhythmias in cardiac surgery (CS) patients. To assess impact on biochemical and
patient-centered outcomes. MATERIALS AND METHODS: We searched MEDLINE, CENTRAL
and EMBASE electronic databases from 1975 to October 2015 using terms related to
magnesium and CS. English-Language RCTs were included involving adults undergoing
CS with parenterally administered magnesium to treat or prevent arrhythmias,
compared to control or standard antiarrythmics. We extracted incidence of
postoperative arrhythmias, termination following magnesium administration and
secondary outcomes (including mortality, length of stay, hemodynamic parameters,
biochemistry). RESULTS: Thirty-five studies were included, with significant
methodological heterogeneity. Atrial fibrillation (AF) was most commonly
reported, followed by ventricular, supraventricular and overall arrhythmia
frequency. Magnesium appeared to reduce AF (RR 0.69, 95% confidence interval
(95%CI) 0.56-0.86, p=0.002), particularly postoperatively (RR 0.51, 95%CI 0.34
0.77, p=0.003) for longer than 24h. Maximal benefit was seen with bolus doses up
to 60mmol. Magnesium appeared to reduce ventricular arrhythmias (RR=0.46, 95%CI
0.24-0.89, p=0.004), with a trend to reduced overall arrhythmias (RR=0.80, 95%CI
0.57-1.12, p=0.191). We found no mortality effect or significant increase in
adverse events. CONCLUSIONS: Magnesium administration post-CS appears to reduce
AF without significant adverse events. There is limited evidence to support
magnesium administration for prevention of other arrhythmias.
PMID- 28688241
TI - ICU-related PTSD - A review of PTSD and the potential effects of collaborative
songwriting therapy.
PMID- 28688239
TI - Successful treatment of toxic epidermal necrolysis using plasmapheresis: A
prospective observational study.
AB - Toxic epidermal necrolysis (TEN) is a rare, severe, life-threatening skin disease
and it requires urgent critical care, including admission to the intensive care
unit (ICU). It is characterized by fatal sequelae and high mortality. Currently,
insufficient evidence exists to support the use of any systemic adjuvant therapy,
such as cyclophosphamide, intravenous immunoglobulin (IVIg), or corticosteroids.
However, plasmapheresis has been increasingly valued by clinicians due to its
significant efficacy and little adverse side effects. To assess the efficacy of
such treatment, 28 patients who were diagnosed with TEN or SJS/TEN overlap were
continuously recruited in the ICU from February 2009 to August 2016. These
patients including both children and adults were randomly divided into two groups
based on whether or not plasmapheresis therapy was performed after admission,
which resulted in a plasmapheresis group (n=13) and a non-plasmapheresis group
(n=15). Severity of the disease and the efficacy of treatments were evaluated by
the severity-of-illness score for TEN. The results indicated that plasmapheresis
may be superior to conventional therapies, such as IVIg or corticosteroids.
Furthermore, plasmapheresis combined with other treatments might not be
advantageous compared to the effect of plasmapheresis alone.
PMID- 28688242
TI - Abnormal renal parenchyma accumulation of 123I MIBG in a child with renal artery
stenosis.
AB - Hypertension is rare in the pediatric population, however renal artery stenosis
(RAS) is an important cause that can be difficult to diagnose. Doppler ultrasound
is the first line imaging modality, with computed tomography and magnetic
resonance imaging as adjunct modalities, all with variable sensitivity for RAS.
The gold standard for evaluation of RAS is invasive selective catheter
angiography. We present a unique multimodality case of abnormal radiotracer
uptake in the renal parenchyma on 123-Iodine metaiodobenzylguanidine (123I MIBG)
scan in a patient with unilateral RAS. RAS is a potential cause of a false
positive MIBG scan, and proper recognition may lead to accurate diagnosis.
PMID- 28688243
TI - Evaluation of white matter hypodensities on computed tomography in stroke
patients using the Fazekas score.
AB - PURPOSE: To assess the reliability of the Fazekas score on brain CT in acute
stroke patients. METHODS: Two raters evaluated the Fazekas score in 157 CT scans
from consecutive patients with acute stroke. RESULTS: The Fazekas scores on brain
CT scans showed consistent (weighted kappa, 0.73) and moderate (weighted kappa,
0.56) interobserver agreement for periventricular and deep white matter areas,
respectively. Intraobserver reliability was substantial for both areas (weighted
kappa, 0.85 and 0.8). CONCLUSION: The Fazekas score on CT can be used to reliably
grade white matter changes, and can be a useful tool when MRI is not available.
PMID- 28688244
TI - Simplified split-bolus intravenous contrast injection technique for pediatric
abdominal CT.
AB - PURPOSE: To investigate pediatric abdominal CT using a simplified split-bolus
(Split group) contrast injection compared with a single bolus (Control group).
METHODS: Radiation dose, image quality and diagnostic accuracy were compared.
RESULTS: Split group demonstrated lower effective dose (2.46 vs. 2.85mSv,
p=0.002) and noise levels in aorta, liver and portal vein (p<0.001). There was
one false-negative case of portal vein obliteration in the Split group.
CONCLUSIONS: A simple method of split-bolus intravenous contrast injection
technique can provide adequate and homogeneous enhancement in pediatric abdominal
CT.
PMID- 28688245
TI - The timing of administration of exogenous glucocorticoid affects 24hour growth
hormone secretion in children.
AB - : Exogenous glucocorticoids may suppress linear growth by affecting the diurnal
secretory rhythm of GH. OBJECTIVE: To assess whether the timing of exogenous
glucocorticoid administration affects GH secretion in children. DESIGN: Four
girls and four boys aged 10.6 to 15.8 (mean 13.2) years with normal weight and
height and pubertal stages I-IV were studied in an open randomized 2-period cross
over trial, with a 1-day un-in, and two 4-day periods of 5mg prednisolone in the
morning or in the evening, respectively, separated by a 3-week washout period. At
run-in and on the last day of each treatment period serum was collected every
20min for 24h for assessment of GH. Secondary analyses were serum levels of IGF-I
and IGFBP-3 (measured every 8h), and IGFBP-1, insulin, and collagen markers PICP,
PINP, ICTP and PIIINP (measured every 2h). RESULTS: Evening prednisolone
suppressed 24hour GH secretion (P=0.016), overnight GH secretion (P=0.023) and
IGF-I (P=0.024) when compared to morning prednisolone, but not when compared to
run-in. Evening prednisolone also increased nocturnal insulin levels as compared
to run-in (P=0.010). Irrespective of time of day, prednisolone increased serum
collagen markers PICP, PIINP, ICTP and PINP (all P<0.05). CONCLUSIONS: Short-term
prednisolone 5mg administered in the morning may alleviate nocturnal GH
suppression as compared to evening administration. In analogy, growth rates are
less affected by morning as compared to evening administration of exogenous
glucocorticoids. In contrast, collagen markers and metabolic indices were not
affected by the timing of prednisolone administration.
PMID- 28688246
TI - Compact shielding design of a portable 241Am-Be source.
AB - A compact shielding tank for portable 241Am-Be neutron source, which is used in
nuclear well logging, was designed according to the Monte Carlo simulation. From
inner to outer, the proposed tank has two shielding layers to shield the high-
and low-energy neutrons. In this study, the shielding properties of several
materials were evaluated. Tungsten was selected as the neutron moderator to build
the inner layer. The thermal neutron absorber in the outer layer was made of
polyethylene containing 1.2% boron carbide. The volume and weight of the new tank
reduced by 86% and 54%, respectively, by using this dual-layer shielding model,
when compared with those of the old shielding tank. Moreover, the simulation
results indicated that the total dose rate anywhere outside the tank is less than
0.025mSv/h and that the intensity of gamma flux at the tank surface becomes
lower.
PMID- 28688247
TI - Lithology and mineralogy recognition from geochemical logging tool data using
multivariate statistical analysis.
AB - The availability of a deep well that penetrates deep into the Ultra High Pressure
(UHP) metamorphic rocks is unusual and consequently offers a unique chance to
study the metamorphic rocks. One such borehole is located in the southern part of
Donghai County in the Sulu UHP metamorphic belt of Eastern China, from the
Chinese Continental Scientific Drilling Main hole. This study reports the results
obtained from the analysis of oxide log data. A geochemical logging tool provides
in situ, gamma ray spectroscopy measurements of major and trace elements in the
borehole. Dry weight percent oxide concentration logs obtained for this study
were SiO2, K2O, TiO2, H2O, CO2, Na2O, Fe2O3, FeO, CaO, MnO, MgO, P2O5 and Al2O3.
Cross plot and Principal Component Analysis methods were applied for lithology
characterization and mineralogy description respectively. Cross plot analysis
allows lithological variations to be characterized. Principal Component Analysis
shows that the oxide logs can be summarized by two components related to the
feldspar and hydrous minerals. This study has shown that geochemical logging tool
data is accurate and adequate to be tremendously useful in UHP metamorphic rocks
analysis.
PMID- 28688248
TI - TL and OSL dose response and stability properties of various commercially glass
samples obtained from Turkey for dosimetric purposes in the UV emission spectral
region.
AB - This paper reports Thermoluminescence (TL) and Optically Stimulated Luminescence
(OSL) dose response characteristics of ten different commercial glass samples
collected from Turkey. Nowadays, glass samples are widely used mostly in objects
of everyday life. The study focuses to both TL and OSL dose responses, through a
dose region within 1 and 512Gy. Lowest detectable dose limit (LDDL) as well as
the respective linearity features of the corresponding dose response curves were
studied for both TL and OSL. Moreover, signal reproducibility and fading
behaviors have also been studied in detail. For specific samples, the lowest
detectable dose was yielded at 2Gy, making thus these samples appropriate for
retrospective dosimetry applications. Nevertheless, based on the features
reported in the present study, the majority of the samples could be possibly used
effectively for dosimetric applications of higher doses in the UV region
emission.
PMID- 28688249
TI - Use of spectral gamma ray as a lithology guide for fault rocks: A case study from
the Wenchuan Earthquake Fault Scientific Drilling project Borehole 4 (WFSD-4).
AB - The main purpose of the Wenchuan Earthquake Fault Scientific drilling project
(WFSD) was to produce an in-depth borehole into the Yingxiu-Beichuan (YBF) and
Anxian-Guanxian faults in order to gain a much better understanding of the
physical and chemical properties as well as the mechanical faulting involved.
Five boreholes, namely WFSD-1, WFSD-2, WFSD-3P, WFSD-3 and WFSD-4, were drilled
during the project entirety. This study, therefore, presents first-hand WFSD-4
data on the lithology (original rocks) and fault rocks that have been obtained
from the WFSD project. In an attempt to determine the physical properties and the
clay minerals of the lithology and fault rocks, this study analyzed the spectral
gamma ray logs (Total gamma ray, Potassium, Thorium and Uranium) recorded in WFSD
4 borehole on the Northern segment of the YBF. The obtained results are presented
as cross-plots and statistical multi log analysis. Both lithology and fault rocks
show a variability of spectral gamma ray (SGR) logs responses and clay minerals.
This study has shown the capabilities of the SGR logs for well-logging of
earthquake faults and proves that SGR logs together with others logs in
combination with drill hole core description is a useful method of lithology and
fault rocks characterization.
PMID- 28688250
TI - On 54Fe neutron cross section importance in iron.
AB - The presented paper aims to evaluate the importance of 54Fe XS in iron by means
of measuring the reaction rates of the selected reactions on 54Fe and measuring a
fast neutron leakage spectra from the iron sphere of 100cm in diameter by a
stilbene scintillation detector with subsequent XS sensitivity analysis. The
reactions involved in the study were 54Fe(n,p) and 54Fe(n,alpha). Measured
neutron induced reaction rates in 54Fe are compared with calculated ones in
different nuclear data libraries. We show that there are notable discrepancies in
54Fe(n,alpha) reaction. The results of the leakage spectra differ significantly
in various libraries, library ENDF/B-VII.1 in region 3.5-7.0MeV gives relatively
good agreement. CIELO library underestimates the result; however JEFF-3.2
overestimates results., 252Cf with the emission rate of 9.53E8 n/s was used as a
neutron source for all experiments involved.
PMID- 28688251
TI - Site-selective covalent reactions on proteinogenic amino acids.
AB - To achieve precise control of the signaling events or to achieve unmistakable
synthesis of biomolecules, nature has evolved organic reactions involving
proteinogenic amino acids with unparalleled site selectivity. For example,
dedicated enzymes accurately dictate the site of post-translational modifications
in signaling proteins, and ribosomes precisely link the C-terminal carboxylic
acid of one unprotected amino acid with the N-terminal amino group of the other
amino acid through spatially confined proximity. For many years, chemists have
been striving to achieve site selectivity on biomolecules by mimicking nature.
Driven by the development of chemoselective protein conjugation reactions,
enzymology and protein-protein interactions, the past decade has witnessed a boom
in site-selective protein conjugation reactions. (In this review, a site
selective protein conjugation reaction is defined as an organic reaction that
targets a single amino acid instead of a kind of amino acids in a protein or a
proteome under physiological conditions, for example, a single cysteine residue
among all of the cysteines.) In this review, we summarize the recent advancements
of bioconjugation reactions that demonstrate this feature of precise site
selectivity, focusing on the reactions of the proteinogenic amino acids
(excluding those at non-coded or non-proteinogenic amino acids that are
introduced to proteins through genetic manipulations).
PMID- 28688252
TI - Organophosphate esters in sediment cores from coastal Laizhou Bay of the Bohai
Sea, China.
AB - Concentrations and vertical distributions of organophosphate esters (OPEs) were
investigated in the sediment cores collected from the Laizhou Bay, Bohai Sea of
China. The total concentrations of OPEs in the sediment core (CA) collected near
the Yellow River Estuary were in the range of 11.8-102ng/g, while the total
concentrations in the sediment core (CB) near a mariculture area were 6.65
41.5ng/g. Significantly high concentrations of OPEs were found in the sediments
near the Yellow River Estuary than those in the mariculture area. Vertical
distributions in the sediment cores demonstrated a recent increase of OPE
emissions, especially for tri-n-butyl phosphate (TnBP), tris (2-chloroethyl)
phosphate (TCEP), and tris (2-chloroisopropyl) phosphate (TCPP). Generally, TCEP
and TCPP were the dominant congeners in the sediment cores, while the profiles of
TnBP were increase in the surface 0-20cm layers of the CA core. OPEs in the CA
core may be remarkably influenced by the discharge of Yellow River, whereas OPEs
in the CB core may originate from the transport through seawater. The remarkable
increase of OPE flame retardants in the surface sediments raises the concern
about their emissions and risks to the environment and indicates the need for
further monitoring.
PMID- 28688253
TI - Effects of apple branch biochar on soil C mineralization and nutrient cycling
under two levels of N.
AB - The incorporation of biochar into soil has been proposed as a strategy for
enhancing soil fertility and crop productivity. However, there is limited
information regarding the responses of soil respiration and the C, N and P cycles
to the addition of apple branch biochar at different rates to soil with different
levels of N. A 108-day incubation experiment was conducted to investigate the
effects of the rate of biochar addition (0, 1, 2 and 4% by mass) on soil
respiration and nutrients and the activities of enzymes involved in C, N and P
cycling under two levels of N. Our results showed that the application of apple
branch biochar at rates of 2% and 4% increased the C-mineralization rate, while
biochar amendment at 1% decreased the C-mineralization rate, regardless of the N
level. The soil organic C and microbial biomass C and P contents increased as the
rate of biochar addition was increased to 2%. The biochar had negative effects on
beta-glucosidase, N-acetyl-beta-glucosaminidase and urease activity in N-poor
soil but exerted a positive effect on all of these factors in N-rich soil.
Alkaline phosphatase activity increased with an increase in the rate of biochar
addition, but the available P contents after all biochar addition treatments were
lower than those obtained in the treatments without biochar. Biochar application
at rates of 2% and 4% reduced the soil nitrate content, particularly in N-rich
soil. Thus, apple branch biochar has the potential to sequester C and improve
soil fertility, but the responses of soil C mineralization and nutrient cycling
depend on the rate of addition and soil N levels.
PMID- 28688254
TI - Monitoring ice variations in Qinghai Lake from 1979 to 2016 using passive
microwave remote sensing data.
AB - Lake ice is a sensitive indicator of climate change. Based on the disparities
between the brightness temperatures of lake ice and water, passive microwave data
can be used to monitor the ice variations of a lake. With focus on the analysis
of long time series variability of lake ice, this study extracts four
characteristic dates related to lake ice (the annual freeze start, freeze
completion, ablation start and ablation completion dates) for Qinghai Lake from
1979 to 2016 using Scanning Multichannel Microwave Radiometer (SMMR) and Special
Sensor Microwave Imager (SSM/I) passive microwave brightness temperature data.
The corresponding freezing duration, ablation duration, complete freezing
duration and ice coverage duration are calculated. Applying Moderate Resolution
Imaging Spectroradiometer (MODIS) daily snow products, the accuracy of the
results derived from passive microwave data is validated. The validation analysis
shows a strong agreement (R2 ranges from 0.70 to 0.85, mean absolute error (MAE)
ranges from 2.25 to 3.94days) in the freeze start, ablation start, and ablation
completion dates derived from the MODIS data and passive microwave data; the ice
coverage duration also has a small error (relative error (RE)=2.95%,
MAE=3.13days), suggesting that the results obtained from passive microwave data
are reliable. The results show that the freezing dates of Qinghai Lake have been
delayed and the ablation dates have advanced. Over 38years, the freeze start date
and freeze completion date have been pushed back by 6.16days and 2.27days,
respectively, while the ablation start date and ablation completion date have
advanced by 11.24days and 14.09days, respectively. The freezing duration and
ablation duration have shortened by 3.89days and 2.85days, respectively, and the
complete freezing duration and ice coverage duration have shortened by 14.84days
and 21.21days, respectively. There is a significant negative correlation between
the ice coverage duration and the mean air temperature in winter.
PMID- 28688255
TI - Natural degradation of roxarsone in contrasting soils: Degradation kinetics and
transformation products.
AB - Roxarsone (ROX) is transformed to more toxic arsenicals after land application of
ROX-containing poultry litter to agricultural soils. To date, no reports have
compared ROX degradation in soils with contrasting properties. In this study, the
impact of different incubation conditions on ROX degradation was investigated in
red (C-Soil) and yellow-brown (H-Soil) soils. The degradation half-lives of
extractable ROX in C-Soil and H-Soil were found to be 130-394d and 4-94d,
respectively, indicating that the extractable ROX degraded faster in H-Soil. This
result stems from the higher organic matter content, more abundant soil microbes,
and lower ROX sorption capacity of H-Soil compared to C-Soil. Degradation of
extractable ROX in both C-Soil and H-Soil was significantly promoted by soil
moisture and exogenous glucose. Exogenous P(V) facilitated degradation of
extractable ROX in C-Soil, but limited effects were observed for H-Soil. HPLC-ICP
MS analysis confirmed that ROX and dimethylarsinic acid were the predominant As
species in soil extracts from 119-day incubated C-Soil and H-Soil, respectively.
Ultimately, minimal transformation of extractable ROX was observed in C-Soil, but
the majority of extractable ROX in H-Soil was biologically transformed. The
differences in degradation of extractable ROX in C-Soil and H-Soil highlight the
key roles of soil properties on the environmental fate of ROX and associated
arsenicals. Results from this study inform the need for comprehensive evaluation
of the ecological risks in organoarsenical-contaminated soils.
PMID- 28688256
TI - Temporal and spatial variation of N2O production from estuarine and marine
shallow systems of Cadiz Bay (SW, Spain).
AB - There is still much uncertainty regarding the global oceanic emissions of N2O,
and particularly emissions from coastal regions, because spatio-temporal datasets
have limited coverage. The concentration of dissolved N2O in surface waters and
the associated fluxes to the atmosphere have been studied in three coastal
systems located near Cadiz Bay (southwestern coast of Spain) over different time
scales. The three systems present different hydrodynamic characteristics (an
estuary and two marine systems) that influence the distribution of N2O in the
water column. Nutrients, oxygen, and particulate organic nitrogen were also
measured to investigate the processes responsible for N2O production in the water
column. Data on dissolved N2O has been obtained in each system from i) two-year
monitoring at fixed station; ii) four seasonal samplings along the longitudinal
length of the system; and iii) daily sampling in summer. The concentration of N2O
ranges between 1.1 and 292.0nM indicating very high spatio-temporal variability.
In general, the concentration of N2O increased during the rainy season associated
with the precipitation regime that, in turn, increases the lateral inputs of
organic matter and nutrients from both natural sources (discharges into rivers
and adjacent marshes) and anthropogenic activities (agriculture, urban effluents
and fish farming). Dissolved N2O also varied with the tides: the highest
concentrations were measured during the ebb, which suggests that the systems
export N2O to the Bay and adjacent Atlantic Ocean. In addition nitrification
seems to be an important process for N2O formation in the water column, which
also explains some of the variability in the dataset. The mean atmospheric flux
of N2O reveals that entire study area was a net source of N2O to the atmosphere.
The fluxes ranged between 0.5 and 313.2MUmolm-2day-1 in the estuarine system, and
between -7.2 and 97.8MUmolm-2day-1 in the two marine systems.
PMID- 28688257
TI - CO2 alters community composition of freshwater phytoplankton: A microcosm
experiment.
AB - The effects of CO2 and related changes in water carbonate chemistry on freshwater
phytoplankton were studied in in situ microcosm experiments, performed in East
Lake Taihu, in August 2013 and April 2014, respectively. The microcosm treatments
represented low (270ppm), present (380ppm), and high (750ppm) pCO2 conditions.
Elevated CO2 decreased pH and increased aqueous CO2 concentrations, and did not
change alkalinity. The maximum reduction of pH was 0.26 when CO2 increased from
current level to 750ppm at the ending of experiment in the spring. The rise of
pCO2 stimulated the growth of phytoplankton, and the net primary production could
increase by 35% when CO2 was elevated from current level to 750ppm in summer.
Interestingly, our results indicated that increasing pCO2 affected phytoplankton
community structure in the microcosms. Cyanobacteria tended to be superior under
high pCO2, with two species Anabaena circinalis and Anabaena eucompacta
benefitting from the rising pCO2. The response of chlorophytes and diatoms to the
rise of pCO2 depended on taxa. In contrast, increased CO2 did not change biomass
or productivity of phytoplankton in spring, when biomass was relatively low.
PMID- 28688258
TI - Projections of NH3 emissions from manure generated by livestock production in
China to 2030 under six mitigation scenarios.
AB - China's rapid urbanization, large population, and increasing consumption of
calorie-and meat-intensive diets, have resulted in China becoming the world's
largest source of ammonia (NH3) emissions from livestock production. This is the
first study to use provincial, condition-specific emission factors based on most
recently available studies on Chinese manure management and environmental
conditions. The estimated NH3 emission temporal trends and spatial patterns are
interpreted in relation to government policies affecting livestock production.
Scenario analysis is used to project emissions and estimate mitigation potential
of NH3 emissions, to year 2030. We produce a 1km*1km gridded NH3 emission
inventory for 2008 based on county-level activity data, which can help identify
locations of highest NH3 emissions. The total NH3 emissions from manure generated
by livestock production in 2008 were 7.3TgNH3.yr-1 (interquartile range from 6.1
to 8.6TgNH3.yr-1), and the major sources were poultry (29.9%), pigs (28.4%),
other cattle (27.9%), and dairy cattle (7.0%), while sheep and goats (3.6%),
donkeys (1.3%), horses (1.2%), and mules (0.7%) had smaller contributions. From
1978 to 2008, annual NH3 emissions fluctuated with two peaks (1996 and 2006), and
total emissions increased from 2.2 to 7.3Tg.yr-1 increasing on average 4.4%.yr-1.
Under a business-as-usual (BAU) scenario, NH3 emissions in 2030 are expected to
be 13.9TgNH3.yr-1 (11.5-16.3TgNH3.yr-1). Under mitigation scenarios, the
projected emissions could be reduced by 18.9-37.3% compared to 2030 BAU
emissions. This study improves our understanding of NH3 emissions from livestock
production, which is needed to guide stakeholders and policymakers to make well
informed mitigation decisions for NH3 emissions from livestock production at the
country and regional levels.
PMID- 28688259
TI - Increased tolerance to oil exposure by the cosmopolitan marine copepod Acartia
tonsa.
AB - Oil contamination is an environmental hazard to marine ecosystems, but marine
organism tolerance to oil after many generations of exposure remains poorly
known. We studied the effects of transgenerational oil exposure on fitness
related traits in a cosmopolitan neritic copepod, Acartia tonsa. Copepods were
exposed to an oil compound, the PAH pyrene, at concentrations of 1, 10, 100 and
100+(the saturated pyrene concentration in seawater)nM over two generations and
measured survival, sex ratio, size at maturity, grazing rate and reproductive
success. Exposure to the pyrene concentration of 100+nM resulted in 100%
mortality before adulthood in the first generation. At the pyrene concentration
of 100nM, pyrene reduced grazing rate, increased mortality, reduced the size of
females and caused lower egg production and hatching success. Importantly, we
found strong evidence for increased tolerance to pyrene exposure in the second
generation: the reduction in size at maturity of females was less pronounced in
the second generation and survival, egg production and hatching success were
recovered to control levels in the second generation. The increased tolerance of
copepods to oil contamination may dampen the direct ecological consequences of a
coastal oil spill, but it raises the concern whether a larger fraction of oil
components accumulated in survived copepods, may be transferred up the food web.
PMID- 28688260
TI - Soil aggregate stability and size-selective sediment transport with surface
runoff as affected by organic residue amendment.
AB - Aggregate breakdown influences the availability of soil particles for size
selective sediment transport with surface runoff during erosive rainfall events.
Organic matter management is known to affect aggregate stability against
breakdown, but little is known about how this translates into rainfall-induced
aggregate fragmentation and sediment transport under field conditions. In this
study, we performed field experiments in which artificial rainfall was applied
after pre-wetting on three pairs of arable soil plots (1.5*0.75m) six weeks after
incorporating a mixture of grass and wheat straw into the topsoil of one plot in
each pair (OI treatment) but not on the other plot (NI treatment). Artificial
rainfall was applied for approximately 2h on each pair at an intensity of 49.1mmh
1. In both treatments, discharge and sediment concentration in the discharge were
correlated and followed a similar temporal pattern after the onset of surface
runoff: After a sharp increase at the beginning both approached a steady state.
But the onset of runoff was more delayed on the OI plots, and the discharge and
sediment concentration were in average only roughly half as high on the OI as on
the NI plots. With increasing discharge the fraction of coarse sediment
increased. This relationship did not differ between the two treatments. Thus, due
to the lower discharge, the fraction of fine particles in the exported sediment
was larger in the runoff from the OI plots than from the NI plots. The later
runoff onset and lower discharge rate was related to a higher initial aggregate
stability on the OI plots. Terrestrial laser scanning proved to be a very
valuable method to map changes in the micro-topography of the soil surfaces. It
revealed a much less profound decrease in surface roughness on the OI than on the
NI plots.
PMID- 28688261
TI - Effect of long term chilled (up to 5weeks) then frozen (up to 12months) storage
at two different sub-zero holding temperatures on beef: 1. Meat quality and
microbial loads.
AB - Beef loins (LL) stored under different chilled-then-frozen storage combinations
(up to 5 and 52weeks, respectively) and two frozen holding temperatures were
evaluated for microbial load and meat quality parameters. We found holding
temperature effects to be negligible, which suggest -12 degrees C could deliver
comparable quality LL to -18 degrees C across these same storage periods. Meat
quality parameters varied significantly, but when compared to existing consumer
thresholds these may not be perceptible, colour being the exception which proved
unacceptable, earlier into retail display when either chilled and subsequent
frozen storage periods were increased. There was insufficient detection of key
spoilage microbes to allow for statistical analysis, potentially due to the
hygienic and commercially representative LL source, although variation in water
activity, glycogen content, pH and other moisture parameters conducive to
microbial proliferation were influenced by chilled-then-frozen storage. These
outcomes could be applied to defining storage thresholds that assure beef quality
within export networks, leveraging market access, and improving product
management.
PMID- 28688262
TI - Intermediate added salt levels as sodium reduction strategy: Effects on chemical,
microbial, textural and sensory quality of polony.
AB - The purpose of this study was to evaluate the use of intermediate added salt
levels (1.33% w/w and 1.84% w/w) as a strategy for reducing the total sodium
content of polony, an emulsified, heat-treated meat product, which is reliant on
the various functions of salt normally included at a 2.5% (w/w) level. Chemical,
microbial, and textural stability over 180days as well as sensory quality were
evaluated. At 1.84% (w/w) added salt content, the product was indistinguishable
from the positive control except for a slightly wetter cutting surface. A level
of 1.33% (w/w) added salt showed similar results, except for a slight variation
in initial moisture content and a much wetter cutting surface. The hardest
texture was achieved at 1.33% (w/w) added salt up to 90days of shelf-life.
Consumers had a slight preference for a lower salt content. From this research it
can be recommended that salt reduction as sole approach in sodium reduction
should be evaluated for meat products in limiting the possibly costly and
negatively perceived use of sodium replacers.
PMID- 28688264
TI - The role of ventromedial prefrontal cortex volume in the association of
expressive suppression and externally oriented thinking.
AB - BACKGROUND: Studies have suggested that expressive suppression (ES) is linked to
externally oriented thinking (EOT) through the ventromedial prefrontal cortex
(vmPFC), and there are gender differences in their association. The present
structural magnetic resonance imaging study was to investigate the neural bases
of ES and EOT and their association in females versus males in a Chinese college
sample. METHODS: A total of 142 participants (83 females) were enrolled, and they
completed the ES subscale of the Emotion Regulation Questionnaire, 20-item
Toronto Alexithymia Scale, and anatomical scanning. Voxel-based morphometry,
region of interest, and whole brain analyses with peak-level significance (family
wise error corrected at p < .05) were conducted to investigate the association of
gray matter volume (GMV) variations with ES and EOT. A bootstrapping analysis was
conducted to examine the role of vmPFC volume in the ES-EOT association. RESULTS:
The ES scores were positively linked to the GMV of the vmPFC in females and
negatively related to right dorsolateral PFC volume in males. The EOT scores were
positively correlated with the GMV of the vmPFC in females and supplementary
motor area in males. Furthermore, vmPFC volume mediated the relationship between
ES and EOT LIMITATIONS: The cross-sectional design limited causal conclusions.
CONCLUSIONS: The vmPFC may be the only neural base of ES and EOT and their
association. In addition, these results were sex-specific.
PMID- 28688265
TI - Association analysis between mitogen-activated protein/extracellular signal
regulated kinase (MEK) gene polymorphisms and depressive disorder in the Han
Chinese population.
AB - BACKGROUND: Recent research findings suggest that BDNF and BDNF signaling
pathways participate in the development of major depressive disorder. Mitogen
activated extracellular signal-regulated kinase (MEK) is the most important
kinase in the extracellular signal-regulated kinase pathway, and the
extracellular signal-regulated kinase pathway is the key signaling pathway of
BDNF, so it may play a role in development of depressive disorder. The aim of
this study is to investigate the association between polymorphisms of the MAP2K1
(also known as MEK) gene and depressive disorder. RESULTS: Three single
nucleotide polymorphisms (SNPs), were significantly associated with depressive
disorder: rs1549854 (p = 0.006), rs1432441 (p = 0.025), and rs7182853 (p =
0.039). When subdividing the sample by gender, two of the SNPs remained
statistically associated with depressive disorder in females: rs1549854 (p =
0.013) and rs1432441 (p = 0.04). CONCLUSION: The rs1549854 and rs1432441
polymorphisms of the MAP2K1 gene may be associated with major depressive
disorder, especially in females. This study is the first to report that the
MAP2K1 gene may be a genetic marker for depressive disorder.
PMID- 28688263
TI - White matter correlates of impaired attention control in major depressive
disorder and healthy volunteers.
AB - BACKGROUND: Major depressive disorder (MDD) is associated with impaired attention
control and alterations in frontal-subcortical connectivity. We hypothesized that
attention control as assessed by Stroop task interference depends on white matter
integrity in fronto-cingulate regions and assessed this relationship using
diffusion tensor imaging (DTI) in MDD and healthy volunteers (HV). METHODS: DTI
images and Stroop task were acquired in 29 unmedicated MDD patients and 16 HVs,
aged 18-65 years. The relationship between Stroop interference and fractional
anisotropy (FA) was examined using region-of-interest (ROI) and tract-based
spatial statistics (TBSS) analyses. RESULTS: ROI analysis revealed that Stroop
interference correlated positively with FA in left caudal anterior cingulate
cortex (cACC) in HVs (r = 0.62, p = 0.01), but not in MDD (r = -0.05, p= 0.79)
even after controlling for depression severity. The left cACC was among 4 ROIs in
fronto-cingulate network where FA was lower in MDD relative to HVs (F(1,41) =
8.87, p = 0.005). Additionally, TBSS showed the same group interaction of
differences and correlations, although only at a statistical trend level.
LIMITATIONS: The modest sample size limits the generalizability of the findings.
CONCLUSIONS: Structural connectivity of white matter network of cACC correlated
with magnitude of Stroop interference in HVs, but not MDD. The cACC-frontal
network, sub-serving attention control, may be disrupted in MDD. Less cognitive
control may include enhanced effects of salience in HVs, or less effective
response inhibition in MDD. Further studies of salience and inhibition components
of executive function may better elucidate the relationship between brain white
matter changes and executive dysfunction in MDD.
PMID- 28688267
TI - Factors affecting lumbar surgery outcome: A nation-wide, population-based
retrospective study.
AB - BACKGROUND: Lower back pain is a very common symptom and treatment strategies
vary according the severity and duration of illness. Surgical approaches are
becoming increasingly popular with the advent of new and less invasive
technologies; however, treatment outcomes are not yet well established on a
population-based level. Taiwan's National Health Insurance Research Database
(NHIRD) is longitudinal and includes 98% of the population since its inception in
1995. The database includes the ICD 9.0 codes (International Classification of
Diseases) of all patients with lower back pain and lumbar surgery; furthermore,
all the prescriptions. METHODS: As part of a population-based cohort study of one
million participants randomly selected from the NHIRD, we analyzed changes in
prescription of analgesics 1 year before and 1 year after lumbar surgery;
comorbidities, such as diabetes, asthma, osteoporosis, arthritis, depression and
anxiety were also analyzed as covariates. A total of 3916 cases were enrolled in
final analysis. RESULTS: Post-operatively, the defined daily dosage (DDD) of
analgesics decreased from a median DDD of 50.0 to a median of 14.2. In a
multivariate model analysis, female, older age, anxiety and asthma were the
significant factors for unfavorable outcome (defined by dosage of analgesics
decreased less than 50% after surgery). CONCLUSIONS: The analgesics significantly
decreased for patients received lumbar surgeries, implying the decreased of pain.
In addition, co-morbidity factors were identified by the failure for analgesics
reduction, such as female, older age, anxiety and asthma. For patients with lower
back pain, these factors should be considered before receiving lumbar surgeries.
PMID- 28688266
TI - Neural - hormonal responses to negative affective stimuli: Impact of dysphoric
mood and sex.
AB - BACKGROUND: Maladaptive responses to negative affective stimuli are pervasive,
including clinically ill and healthy people, and men and women respond
differently at neural and hormonal levels. Inspired by the Research Domain
Criteria initiative, we used a transdiagnostic approach to investigate the impact
of sex and dysphoric mood on neural-hormonal responses to negative affective
stimuli. METHODS: Participants included 99 individuals with major depressive
disorder, psychosis and healthy controls. Functional magnetic resonance imaging
(fMRI) was complemented with real-time acquisition of hypothalamo-pituitary
adrenal (HPA) and -gonadal (HPG) hormones. fMRI data were analyzed in SPM8 and
task-related connectivity was assessed using generalized psychophysiological
interaction. RESULTS: Across all participants, elevated cortisol response
predicted lower brain activity in orbitofrontal cortex and hypothalamus-amygdala
connectivity. In those with worse dysphoric mood, elevated cortisol response
predicted lower activity in hypothalamus and hippocampus. In women, elevated
cortisol response was associated with lower activity in medial prefrontal cortex
and low hypothalamo-hippocampal connectivity. In women with high dysphoric mood,
elevated cortisol response was associated with low hypothalamo-hippocampal
connectivity. There were no interactions with diagnosis or medication.
LIMITATIONS: There was limited power to correct for multiple comparisons across
total number of ROIs and connectivity targets; cortisol responses were relatively
low. CONCLUSIONS: We conclude that the pathophysiology in neural-hormonal
responses to negative affective stimuli is shared across healthy and clinical
populations and varies as a function of sex and dysphoric mood. Our findings may
contribute to the development of hormonal adjunctive therapeutics that are sex
dependent, underscoring the importance of one's sex to precision medicine.
PMID- 28688268
TI - TFEB-mediated activation of the lysosome-autophagy system affects the
transduction efficiency of adeno-associated virus 2.
AB - Adeno-associated virus (AAV)-mediated gene transfer is an appealing therapeutic
option due to AAV's safety profile. Effective delivery of AAV's genetic cargo to
the nucleus, however, requires evasion of host cell barriers, including cellular
clearance mechanisms mediated by the lysosome-autophagy system. We used AAV
serotype 2 to monitor the autophagic response to cellular internalization of AAV
and to characterize the effect of AAV-induced activation of autophagy on
transgene expression. We found AAV2 internalization to induce activation of
transcription factor EB, a master regulator of autophagy and lysosomal
biogenesis, and upregulation of the lysosome-autophagy system. We showed that
AAV2-induced activation of autophagy parallels a reduction in transgene
expression, but also an increase in autophagic clearance of protein aggregates.
These results can inform the design of AAV vectors with autophagy-modulating
properties for applications ranging from the design of efficient gene delivery
vectors to the treatment of diseases characterized by accumulation of autophagic
cargo.
PMID- 28688269
TI - Nature based solution for improving mental health and well-being in urban areas.
AB - The general disproportion of urban development and the socio-economical crisis in
Serbia, followed by a number of acute and chronic stressors, as well as years of
accumulated trauma, prevented the parallel physical, mental and social adaptation
of society as a whole. These trends certainly affected the quality of mental
health and well-being, particularly on the vulnerable urban population,
increasing the absolute number of people with depression, stress and
psychosomatic disorders. This study was pioneering in Serbia and was conducted in
collaboration with the Faculty of Forestry, the Institute of Mental Health and
the Botanical Garden in Belgrade, in order to understand how spending time and
performing horticulture therapy in specially designed urban green environments
can improve mental health. The participants were psychiatric patients (n=30),
users of the day hospital of the Institute who were randomly selected for the
study, and the control group, assessed for depression, anxiety and stress before
and after the intervention, using a DASS21 scale. During the intervention period
the study group stayed in the Botanical garden and participated in a special
programme of horticulture therapy. In order to exclude any possible "special
treatment'' or ''placebo effect", the control group was included in occupational
art therapy while it continued to receive conventional therapy. The test results
indicated that nature based therapy had a positive influence on the mental health
and well-being of the participants. Furthermore, the difference in the test
results of the subscale stress before and after the intervention for the study
group was F1.28 = 5.442 and p<;.05. According to socio demographic and clinical
variables, the interesting trend was recorded on the subscale of anxiety showing
that the male participants in the study group were more anxious, with the most
pronounced inflection noted on this scale after treatment. The results of this
study have shown that recuperation from stress, depression and anxiety was
possible and much more complete when participants were involved in horticulture
therapy as a nature-based solution for improving mental health.
PMID- 28688270
TI - Simultaneous quantitative analysis of polyethylene glycol (PEG), PEGylated
paclitaxel and paclitaxel in rats by MS/MSALL technique with hybrid quadrupole
time-of-flight mass spectrometry.
AB - PEGylation is practically one of most important modifications of drugs including
small molecules, peptides and proteins, which has been proven to dramatically
improve physicochemical properties and pharmacokinetic behavior of the PEGylated
drugs. However, it is a challenge currently to quantitatively analyze PEG and
PEGylated drugs by various analytical methods, even mass spectrometry because of
multiple parent ion distribution of PEG caused by its polydispersity of molecular
weight. Here we developed a robust method with MS/MSALL technique using
electrospray ionization (ESI) source coupled high resolution Quadrupole Time-of
Flight (Q-TOF) mass spectrometry for the quantification of PEG2K-Paclitaxel (PEG
PTX) and its two metabolites, PEG and Paclitaxel (PTX). The analysis was
performed on a 300SB-C18 column with acetonitrile and 0.1% formic acid as the
mobile phase. Samples were simply prepared by protein precipitation in a small
quantity of plasma (50MUL). Calibration curve was linear within the range of 50.0
4000ng/mL for PEG and PEG-PTX and 1.0-1000ng/mL for PTX. The intra- and inter-day
precisions were 3.2-6.9% and 3.1-6.9% for PEG, 4.1-7.8% and 4.0-9.9% for PEG-PTX,
and 3.3-4.8% and 3.1-6.9% for PTX, respectively. The recoveries were greater than
90% with low matrix effects. Afterwards, the newly developed method was
successfully applied to support a preclinical pharmacokinetic study in six rats
after single intravenous injection of PEG-PTX (51.7mg/kg).
PMID- 28688271
TI - Agarose based large molecular systems: Synthesis of fluorescent aromatic agarose
amino acid nano-conjugates - their pH-stimulated structural variations and
interactions with BSA.
AB - Two new nano-sized fluorescent 6-amino agarose naphthalic acid half ester
derivatives were synthesized (ca.60% yields) employing 1,8- and 2,3-naphthalic
acid anhydrides (1,8-AANE, and 2,3-AANE respectively). These large nano molecular
frameworks (DLS 3 & 100 nm, and 3 & 152 nm respectively) contains amino,
naphthalate half-ester carboxyl groups at the C-6 positions of the 1,3-beta-D
galactopyranose moieties of the agarose backbone (overall DS 0.94). Structures
were characterized (FT-IR, and 13C &1H NMR spectrometries). These materials
mimicked a large protein conjugate (GPC 123, and 108 kDa) exhibiting pH
responsive conformational variations (optical rotatory dispersion), offering a
mixed solubility pattern like a soluble random coil (pH 4-10), and precipitate
(pH 2) formation. With bovine serum albumin 1,8- and 2,3-AANE showed
complexation, and decomplexation at pH 5.2, and 6.8 respectively. However, they
showed decomplexation, and complexation respectively at pH 10 (circular
dichroism). These fluorogenic systems may be of prospective utility as chiral
sensors and in the realms demanding the virtues of preferential protein bindings.
PMID- 28688272
TI - Does pain in the masseter and anterior temporal muscles influence maximal bite
force?
AB - OBJECTIVE: The aim of this study was to evaluate changes in pain and muscle
force, and the relationship between them, in patients with muscle pain and
bruxism, prior to and after treatment. METHODS: Thirty women with bruxism and
myofascial pain (Ia) were included in this study. Sleep bruxism diagnosis was
made based on clinical diagnostic criteria, and awake bruxism diagnosis was made
by patient questionnaires and the presence of tooth wear. The diagnosis of
myofascial pain was established according to the Research Diagnostic Criteria for
Temporomandibular Disorders (RDC-TMD). Dentulous or partially edentulous patients
(rehabilitated with conventional fixed prostheses) were included in the study
according to the inclusion and exclusion criteria. The pain treatment protocol
included occlusal splints, patient education, and physiotherapy for 30days. Bite
force was measured using a dynamometer at the central incisor and the first molar
regions on both sides. The exams were performed at baseline, after 7days, and
30days after treatment. The Wilcoxon test was used to compare patient pain level
response among the periods analyzed in the study. Bite force data were submitted
to two-way repeated-measures ANOVA, followed by the Tukey HSD test (p<0.05). A
simple regression analysis was performed to verify the relation between pain
level and bite force. RESULTS: Results revealed that there was a statistical
difference in pain level over time for both muscles and sides (p<0.01). In the
molar region, the bite force exhibited significantly higher values after 30days
of treatment, when compared with the baseline (p<0.001). There was a correlation
between pain level and bite force only for the temporal muscle in all periods
analyzed (p<0.05). There was no strong correlation in the response level points
to support the association of pain and bite force. CONCLUSIONS: Pain level
decreased and bite force increased in the molar region after treatment. No strong
correlation or dispersion in the relationship between pain levels and bite force
was seen in women with myofascial pain and bruxism.
PMID- 28688274
TI - Discovery of novel naphthoquinone derivatives as inhibitors of the tumor cell
specific M2 isoform of pyruvate kinase.
AB - Pyruvate kinase M2 (PKM2) is a rate-limiting enzyme of the glycolytic pathway
which is highly expressed in cancer cells. Cancer cells rely heavily on PKM2 for
anabolic and energy requirements, and specific targeting of PKM2 therefore has
potential as strategy for cancer therapy. Here, we report the synthesis and
biologic evaluation of novel naphthoquinone derivatives as selective small
molecule inhibitors of PKM2. Some target compounds, such as compound 3k,
displayed more potent PKM2 inhibitory activity than the reported optimal PKM2
inhibitor shikonin. The well performing compound 3k also showed nanomolar
antiproliferative activity toward a series of cancer cell lines with high
expression of PKM2 including HCT116, Hela and H1299 with IC50 values ranging from
0.18 to 1.56 MUM. Moreover, compound 3k exhibited more cytotoxicity on cancer
cells than normal cells. The identification of novel potent small molecule
inhibitors of PKM2 not only offers candidate compounds for cancer therapy, but
also provides a tool with which to evaluate the function of PKM2 in depth.
PMID- 28688273
TI - Leucine rich repeat kinase 2 (LRRK2) inhibitors based on indolinone scaffold:
Potential pro-neurogenic agents.
AB - Leucine-rich repeat kinase 2 (LRRK2) is one of the most pursued targets for
Parkinson's disease (PD) therapy. Moreover, it has recently described its role in
regulating Wnt signaling and thus, it may be involved in adult neurogenesis. This
new hypothesis could give rise to double disease-modifying agents firstly by the
benefits of inhibiting LRRK2 and secondly by promoting adult neurogenesis. Herein
we report, the design, synthesis, biological evaluation, SAR and potential
binding mode of indoline-like LRRK2 inhibitors and their preliminary neurogenic
effect in neural precursor cells isolated from adult mice ventricular
subventricular zone. These results open new therapeutic horizons for the use of
LRRK2 inhibitors as neuroregenerative agents. Moreover, the indolinone
derivatives here prepared, inhibitors of the kinase activity of LRRK2, may be
considered as pharmacological probes to study the potential neuroregeneration of
the damaged brain.
PMID- 28688275
TI - Design and synthesis of conformationally constrained salinomycin derivatives.
AB - Two conformationally restricted salinomycin derivatives by tethering the hydroxyl
groups at C1 and C20 with different chain length were designed and synthesized.
The cyclic derivatives showed better biological activities than C1/C20 modified
derivatives, indicating the importance of the compact conformation for the ion
binding capacity. In addition, the length of the connective chain plays critical
role in the biological activities, thus cyclic the derivative 7 preserved some
pharmacological activity but derivative 5 with two carbon atom shorter chain
showed significantly reduced activity. The conformations of the two cyclic
salinomycin derivatives were analyzed by ROESY spectrum in DMSO-d6, indicating
derivative 7 may adopt more appropriate conformations for the coordinate with
alkali metal ion than derivative 5, which has a closer distance between H3 and
H25.
PMID- 28688276
TI - Novel 2-(2-alkylthiobenzenesulfonyl)-3-(phenylprop-2-ynylideneamino)guanidine
derivatives as potent anticancer agents - Synthesis, molecular structure, QSAR
studies and metabolic stability.
AB - A series of new 2-(2-alkylthiobenzenesulfonyl)-3-(phenylprop-2
ynylideneamino)guanidine derivatives have been synthesized and evaluated in vitro
by MTT assays for their antiproliferative activity against cell lines of colon
cancer HCT-116, cervical cancer HeLa and breast cancer MCF-7. The obtained
results indicated that these compounds display prominent cytotoxic effect. The
best anticancer properties have been observed for derivatives 44 (IC50 = 6-18
MUM) and 45 (IC50 = 8-14 MUM). Very good results of antiproliferative assays have
been also shown for compounds 26, 36, and 46 and noticeable anticancer profile
has been found for set of derivatives 34-39. Based on results of MTT assays the
structure-activity relationships have been drawn. More in-depth biological
research revealed that compounds 26, 33, 37, 39, 41 and 43 display cytotoxic
effect only against cancer cells and do not inhibit the growth of non-malignant
HaCaT cells. Furthermore, the novel series of derivatives have shown good
metabolic stability, especially among the pharmacologically active compounds. To
obtain a deeper insight into the molecular description of compounds activity the
QSAR studies have been applied. Support vector machines (SVM) have been used to
developed QSAR models for predicting the anti-proliferative activity of novel
derivatives. The obtained SVM models have shown prognostic ability for HCT-116
and HeLa cell lines and as a result these models may be useful for further
development of structurally similar derivatives with better biological
properties.
PMID- 28688277
TI - Synthesis, antitumor activity and CDK1 inhibiton of new thiazole nortopsentin
analogues.
AB - A new series of thiazole nortopsentin analogues was conveniently synthesized with
fair overall yields. The antiproliferative activity of the new derivatives was
tested against different human tumor cell lines of the NCI full panel. Four of
them showed good antitumor activity with GI50 values from micro to nanomolar
level. The mechanism of the antiproliferative effect of these derivatives, was
pro-apoptotic, being associated with externalization of plasma membrane
phosphatidylserine and DNA fragmentation. The most active and selective of the
new thiazoles confined viable cells in G2/M phase and markedly inhibited in vitro
CDK1 activity.
PMID- 28688278
TI - Design, synthesis, and biological evaluation of optimized phthalazine derivatives
as hedgehog signaling pathway inhibitors.
AB - We report herein the design and synthesis of a series of optimized phthalazine
compounds as novel hedgehog signaling pathway inhibitors. The 4-methylamino
piperidine moiety of Taladegib was replaced by different four, five or six
membered azacycle or azaspirocycle building blocks. The in vitro Gli-luciferase
assay results demonstrate that the scaffold hopping in this region afforded
significant influences on Hh pathway inhibition. Pyrrolidin-3-amine moiety was
found to be the best linker between pharmacophores phthalazine and fluorine
substituted benzoyl group. Meanwhile the optimization of 1-methyl-1H-pyrazol by
different aromatic rings was also investigated and the SAR was described. Many
new derivatives were found to show potent Hh signaling inhibitory activity with
nanomolar IC50 values. Among these compounds, compound 23b showed the highest
inhibitory potency with an IC50 value of 0.17 nM, which was 35-fold more potent
than the lead compound Taladegib and 23-fold more potent than the marketed drug
Vismodegib. The selected compounds 23a and 23b also possess potent antitumor
activities against medulloblastoma cells proliferation in vitro. In vivo efficacy
of 23b in a ptch+/-p53-/- mouse medulloblastoma allograft model also indicated
encouraging results.
PMID- 28688279
TI - Synthesis of novel 5-(aroylhydrazinocarbonyl)escitalopram as cholinesterase
inhibitors.
AB - A novel series of 5-(aroylhydrazinocarbonyl)escitalopram (58-84) have been
designed, synthesized and tested for their inhibitory potential against
cholinesterases. 3-Chlorobenzoyl- (71) was found to be the most potent compound
of this series having IC50 1.80 +/- 0.11 MUM for acetylcholinesterase (AChE)
inhibition. For the butyrylcholinesterase (BChE) inhibition, 2-bromobenzoyl- (76)
was the most active compound of the series with IC50 2.11 +/- 0.31 MUM. Structure
activity relationship illustrated that mild electron donating groups enhanced
enzyme inhibition while electron withdrawing groups reduced the inhibition except
o-NO2. However, size and position of the substituents affected enzyme
inhibitions. . In docking study of AChE, the ligands 71, 72 and 76 showed the
scores of 5874, 5756 and 5666 and ACE of -64.92,-203.25 and -140.29 kcal/mol,
respectively. In case of BChE, ligands 71, 76 and 81 depicted high scores 6016,
6150 and 5994 with ACE values -170.91, -256.84 and -235.97 kcal/mol,
respectively.
PMID- 28688280
TI - Synthesis of sulfamoylbenzamide derivatives as HBV capsid assembly effector.
AB - The synthesis of novel series of sulfamoylbenzamides as HBV capsid assembly
effector is reported. The structure was divided into five parts which were
independently modified as part of our lead optimization. All synthesized
compounds were evaluated for their anti-HBV activity and toxicity in human
hepatocytes, lymphocytes and other cells. Additionally, we assessed their effect
on HBV cccDNA formation in an HBeAg reporter cell-based assay. Among the 27
compounds reported, several analogs exhibited submicromolar activities and
significant reduction of HBeAg secretion. Selected compounds were studied under
negative-stain electron microscopy for their ability to disrupt the HBV capsid
formation. Structures were modeled into a binding site recently identified in the
HBV capsid protein for similar molecules to rationalize the structure-activity
relationships for this family of compounds.
PMID- 28688281
TI - Novel celastrol derivatives with improved selectivity and enhanced antitumour
activity: Design, synthesis and biological evaluation.
AB - Celastrol is one of the most active antitumour compounds among the natural
triterpenoids. It has been reported to be highly active against a wide variety of
tumours and to affect multiple cellular pathways. A series of new celastrol
derivatives, including compounds bearing a urea group, have been synthesised and
analysed for their biological activity against human cancer cell lines. Several
compounds presented a stronger growth inhibition effect than celastrol on the
cell lines studied. Among them, compound 24 was the most promising derivative, as
it exhibited both a remarkable antiproliferative activity and an improved
selectivity in tumour versus non-tumour cells. The anticancer molecular mechanism
of compound 24 in the human ovary cancer cell line SKOV-3 was further studied and
the results showed that compound 24 induced apoptosis through the activation of
the extrinsic death receptor pathway. Interestingly, the results revealed that
compound 24 might be able to decrease the levels of dysfunctional p53. The assays
also suggested that compound 24 is an Hsp90 inhibitor, and that the Akt/mTOR
pathway might be involved in the downstream regulation that leads to its
antiproliferative activity. Moreover, a synergistic anticancer effect was
evidenced when SKOV-3 cells were simultaneously treated with compound 24 and
cisplatin. Taken together, these results suggest that compound 24 may be a
promising lead for the development of new cancer therapies.
PMID- 28688282
TI - Social cognition interventions for people with schizophrenia: a systematic review
focussing on methodological quality and intervention modality.
AB - BACKGROUND: People with a diagnosis of schizophrenia have significant social and
functional difficulties. Social cognition was found to influences these outcomes
and in recent years interventions targeting this domain were developed. This
paper reviews the existing literature on social cognition interventions for
people with a diagnosis of schizophrenia focussing on: i) comparing focussed
(i.e. targeting only one social cognitive domain) and global interventions and
ii) studies methodological quality. METHOD: Systematic search was conducted on
PubMed and PsycInfo. Studies were included if they were randomised control
trials, participants had a diagnosis of schizophrenia or schizoaffective
disorder, and the intervention targeted at least one out of four social cognition
domains (i.e. theory of mind, affect recognition, social perception and
attribution bias). All papers were assessed for methodological quality.
Information on the intervention, control condition, study methodology and the
main findings from each study were extracted and critically summarised. RESULTS:
Data from 32 studies fulfilled the inclusion criteria, considering a total of
1440 participants. Taking part in social cognition interventions produced
significant improvements in theory of mind and affect recognition compared to
both passive and active control conditions. Results were less clear for social
perception and attributional bias. Focussed and global interventions had similar
results on outcomes. Overall study methodological quality was modest. There was
very limited evidence showing that social cognitive intervention result in
functional outcome improvement. CONCLUSIONS: The evidence considered suggests
that social cognition interventions may be a valuable approach for people with a
diagnosis of schizophrenia. However, evidence quality is limited by measure
heterogeneity, modest study methodology and short follow-up periods. The findings
point to a number of recommendations for future research, including measurement
standardisation, appropriately powered studies and investigation of the impact of
social cognition improvements on functioning problems.
PMID- 28688283
TI - Central focused convolutional neural networks: Developing a data-driven model for
lung nodule segmentation.
AB - Accurate lung nodule segmentation from computed tomography (CT) images is of
great importance for image-driven lung cancer analysis. However, the
heterogeneity of lung nodules and the presence of similar visual characteristics
between nodules and their surroundings make it difficult for robust nodule
segmentation. In this study, we propose a data-driven model, termed the Central
Focused Convolutional Neural Networks (CF-CNN), to segment lung nodules from
heterogeneous CT images. Our approach combines two key insights: 1) the proposed
model captures a diverse set of nodule-sensitive features from both 3-D and 2-D
CT images simultaneously; 2) when classifying an image voxel, the effects of its
neighbor voxels can vary according to their spatial locations. We describe this
phenomenon by proposing a novel central pooling layer retaining much information
on voxel patch center, followed by a multi-scale patch learning strategy.
Moreover, we design a weighted sampling to facilitate the model training, where
training samples are selected according to their degree of segmentation
difficulty. The proposed method has been extensively evaluated on the public LIDC
dataset including 893 nodules and an independent dataset with 74 nodules from
Guangdong General Hospital (GDGH). We showed that CF-CNN achieved superior
segmentation performance with average dice scores of 82.15% and 80.02% for the
two datasets respectively. Moreover, we compared our results with the inter
radiologists consistency on LIDC dataset, showing a difference in average dice
score of only 1.98%.
PMID- 28688284
TI - Social evaluation of intentional, truly accidental, and negligently accidental
helpers and harmers by 10-month-old infants.
AB - Whereas adults largely base their evaluations of others' actions on others'
intentions, a host of research in developmental psychology suggests that younger
children privilege outcome over intention, leading them to condemn accidental
harm. To date, this question has been examined only with children capable of
language production. In the current studies, we utilized a non-linguistic puppet
show paradigm to examine the evaluation of intentional and accidental acts of
helping or harming in 10-month-old infants. In Experiment 1 (n=64), infants
preferred intentional over accidental helpers but accidental over intentional
harmers, suggestive that by this age infants incorporate information about
others' intentions into their social evaluations. In Experiment 2 (n=64), infants
did not distinguish "negligently" accidental from intentional helpers or harmers,
suggestive that infants may find negligent accidents somewhat intentional. In
Experiment 3 (n=64), we found that infants preferred truly accidental over
negligently accidental harmers, but did not reliably distinguish negligently
accidental from truly accidental helpers, consistent with past work with adults
and children suggestive that humans are particularly sensitive to negligently
accidental harm. Together, these results imply that infants engage in intention
based social evaluation of those who help and harm accidentally, so long as those
accidents do not stem from negligence.
PMID- 28688285
TI - A strategy for actualization of active targeting nanomedicine practically
functioning in a living body.
AB - Designing nanocarriers with active targeting has been increasingly emphasized as
for an ideal delivery mechanism of anti-cancer therapeutic agents, but the
actualization has been constrained by lack of reliable strategy ultimately
applicable. Here, we designed and verified a strategy to achieve active targeting
nanomedicine that works in a living body, utilizing animal models bearing a
patient's tumor tissue and subjected to the same treatments that would be used in
the clinic. The concept for this strategy was that a novel peptide probe and its
counterpart protein, which responded to a therapy, were identified, and then the
inherent ability of the peptide to target the designated tumor protein was used
for active targeting in vivo. An initial dose of ionizing radiation was locally
delivered to the gastric cancer (GC) tumor of a patient-derived xenograft mouse
model, and phage-displayed peptide library was intravenously injected. The
peptides tightly bound to the tumor were recovered, and the counterpart protein
was subsequently identified. Peptide-conjugated liposomal drug showed
dramatically improved therapeutic efficacy and possibility of diagnostic imaging
with radiation. These results strongly suggested the potential of our strategy to
achieve in vivo functional active targeting and to be applied clinically for
human cancer treatment.
PMID- 28688286
TI - Co-delivery of a growth factor and a tissue-protective molecule using elastin
biopolymers accelerates wound healing in diabetic mice.
AB - Growth factor therapy is a promising approach for chronic diabetic wounds, but
strategies to efficiently and cost-effectively deliver active molecules to the
highly proteolytic wound environment remain as major obstacles. Here, we re
engineered keratinocyte growth factor (KGF) and the cellular protective peptide
ARA290 into a protein polymer suspension with the purpose of increasing their
proteolytic resistance, thus their activity in vivo. KGF and ARA290 were fused
with elastin-like peptide (ELP), a protein polymer derived from tropoelastin,
that confers the ability to separate into a colloidal suspension of liquid-like
coacervates. ELP fusion did not diminish peptides activities as demonstrated by
ability of KGF-ELP to accelerate keratinocyte proliferation and migration, and
ARA290-ELP to protect cells from apoptosis. We examined the healing effect of
ARA290-ELP and KGF-ELP alone or in combination, in a full-thickness diabetic
wound model. In this model, ARA290-ELP was found to accelerate healing, notably
by increasing angiogenesis in the wound bed. We further showed that co-delivery
of ARA290 and KGF, with the 1:4 KGF-ELP to ARA290-ELP ratio, was the most
effective wound treatment with the fastest healing rate, the thicker granulation
tissue and regenerated epidermis after 28 days. Overall, this study shows that
ARA290-ELP and KGF-ELP constitute promising new therapeutics for treatment of
chronic wounds.
PMID- 28688288
TI - Enhanced osteogenic activity of poly(ester urea) scaffolds using facile post-3D
printing peptide functionalization strategies.
AB - Additive manufacturing has the potential to revolutionize regenerative medicine,
but the harsh thermal or photochemical conditions during the 3D printing process
limit the inclusion of drugs, growth factors and other biologics within the
resulting scaffolds. Functionalization strategies that enable specific placement
of bioactive species on the surface of 3D printed structures following the
printing process afford a promising approach to sidestep the harsh conditions and
incorporate these valuable bioactive molecules with precise control over
concentration. Herein, resorbable polymer scaffolds were prepared from propargyl
functionalized L-phenylalanine-based poly(ester urea)s (PEUs). Osteogenic growth
peptide (OGP) or bone morphogenic protein-2 (BMP-2) peptides were immobilized on
PEU scaffolds through surface available propargyl groups via copper-catalyzed
azide alkyne cycloaddition (CuAAC) post 3D printing. The presence of either OGP
or BMP-2 significantly enhanced hMSCs osteogenic differentiation compared to
unfunctionalized scaffolds.
PMID- 28688287
TI - Riboflavin-containing telodendrimer nanocarriers for efficient doxorubicin
delivery: High loading capacity, increased stability, and improved anticancer
efficacy.
AB - We have developed two linear-dendritic telodendrimers (TDs) with rational design
using amphiphilic riboflavin (Rf) as building blocks for efficient doxorubicin
(DOX) delivery. Micellar TD nanoparticles (NPs) are composed of a hydrophilic
polyethylene glycol (PEG) shell and a Rf-containing affinitive core for DOX
encapsulation. Strong DOX-Rf interactions and amphiphilic Rf structure render
these nanocarriers with an ultra-high DOX loading capacity (>1/1, DOX/TD, w/w),
~100% loading efficiency, the sustained drug release and the optimal particle
sizes (20-40 nm) for efficient tumor-targeted drug delivery. These
nanoformulations significantly prolonged DOX circulation time in the blood
without the accelerated clearance observed after multiple injections. DOX-TDs
target several types of tumors efficiently in vivo, e.g. Raji lymphoma, MDA-MB
231 breast cancer, and SKOV-3 ovarian cancer. In vivo maximum tolerated dose
(MTD) of DOX was increased by 2-2.5 folds for the nanoformulations in mice
relative to those of free DOX and Doxil(r). These nanoformulations significantly
inhibited tumor growth and prolonged survival of mice bearing SKOV-3 ovarian
cancer xenografts. In summary, Rf-containing nanoformulations with high DOX
loading capacity, improved stability and efficient tumor targeting lead to
superior antitumor efficacy, which merit the further development for clinical
application.
PMID- 28688289
TI - Antiviral activity of a synthesized shikonin ester against influenza A (H1N1)
virus and insights into its mechanism.
AB - This study aimed to examine the antiviral effects of shikonin ester ((R)-1-(5, 8
dihydroxy-1,4-dioxo-1,4-dihydronaphthalen-2-yl)-4-methylpent-3-en-1-yl3-(1H-
indol-3-yl) propanoate (PMM-034) against influenza A (H1N1) virus. We
investigated PMM-034 anti-H1N1 activity and its effect on caspase 3 gene
expression during cellular apoptosis after influenza virus infection in vitro.
Neuraminidase (NA) inhibition was assessed in comparison with oseltamivir in the
influenza virus standard strains A/PR/8/34 to understand the viral mechanism.
MDCK and A549 cells were used to investigate influenza viral infection and the
structure-activity relationship between PMM-034 and NA was evaluated by
pharmacophore-based docking modeling. The production of viral protein was tested
by western blot. A/PR/8/34 induced cell inhibition but this was reduced by PMM
034 to 16MUg/mL and this showed a selective index of 10mM. PMM-034 inhibited NA
in a dose dependent manner, similar to oseltamivir inhibition. A sharp decrease
in viral nucleocapsid protein mRNA was observed in infected cells after treatment
with PMM-034. Apoptosis of infected A459 cells was inhibited by PMM-034 with
decreased caspase 3 levels. ARG 118, ARG 152, ARG 371 and GLU 227 in the binding
pocket of NA bound to PMM-034 in the docking model. Taken together, these results
suggest PMM-034 shikonin ester blocked H1N1 infection and might be a potential
anti-H1N1 drug.
PMID- 28688290
TI - The efficacy of plant extract and bioactive compounds approaches in the treatment
of pulmonary fibrosis: A systematic review.
AB - Pulmonary fibrosis (PF) is a lethal, chronic and progressive respiratory disease
leading to interstitial lung damage and serious breathing problems. The
pathogenic mechanism involves activation, migration, proliferation and
differentiation of fibroblasts into myofibroblats inducing extracellular matrix
accumulation that destroy lung parenchyma. Available antifibrotic treatment
options are limited to Pirfenidone and Nintedanib that prevent deterioration
without an improvement of this disease. The use of plant extracts and natural
bioactive compounds for the treatment of PF has been known for more than thirty
years in China. Nowadays, phytotherapy has gained a considerable attention in the
treatment of PF both in vivo and in vitro using bleomycin (BLM)-induced lung
inflammation, oxidative stress and pulmonary fibrosis in rats. In this review, we
aimed to focus on the protective effects and the mechanisms of action of several
plant extracts described by various research works for the treatment of PF.
PMID- 28688291
TI - Neonatal Assessment Visual European Grid (NAVEG): Unveiling neurological risk.
PMID- 28688292
TI - Impact of air masses on the distribution of 210Pb in the southeast of Iberian
Peninsula air.
AB - The current research has been developed in the southern of the Iberian Peninsula
in order to better understand the atmospheric processes and also the influence of
the air masses origin and pathways in the transport of 210Pb-aerosols in the
atmosphere. Simultaneous measurements of the radionuclides 7Be and 210Pb on
airborne have been routinely carried out at Granada (Spain 37.177N, 3.598 W, 687
m a.s.l.) from 2010 to 2014. The long term monitoring evolution on 210Pb is
discussed in this study and also the useful ratio 7Be/210Pb. The maximum monthly
activity concentration for 210Pb at ground level in Granada was detected during
summer and early autumn (September), whereas minimum activity was measured in the
winter. The monthly mean activity concentration for 210Pb was 617.8 +/- 33.0
MUBq.m-3. The results show that the annual average 210Pb concentrations in
samples collected during the same period were almost constant. The lowest
activity concentration for 210Pb are associated with maritime air masses coming
from Atlantic and Norwest of Spain, while the highest activity concentrations for
this radiotracers were positively correlated with the arrival of mineral dust
linked to continental air masses coming from Mediterranean, Africa and Local
area. The concentrations values show a nice agreement with the relevant reported
results.
PMID- 28688293
TI - A new parameter for quantifying the variability of surface electromyographic
signals during gait: The occurrence frequency.
AB - Natural variability of myoelectric activity during walking was recently analyzed
considering hundreds of strides. This allowed assessing a parameter seldom
considered in classic surface EMG (sEMG) studies: the occurrence frequency,
defined as the frequency each muscle activation occurs with, quantified by the
number of strides when a muscle is recruited with that specific activation
modality. Aim of present study was to propose the occurrence frequency as a new
parameter for assessing sEMG-signal variability during walking. Aim was addressed
by processing sEMG signals acquired from Gastrocnemius Lateralis, Tibialis
Anterior, Rectus Femoris and Biceps femoris in 40 healthy subjects in order to:
(1) show that occurrence frequency is not correlated with ON/OFF instants
(Rmean=0.11+/-0.07; P>0.05) and total time of activation (Rmean=0.15+/-0.08;
P>0.05); (2) confirm the above results by two handy examples of application
(analysis of gender and age) which highlighted that significant (P<0.05) gender
related and age-related differences within population were detected in occurrence
frequency, but not in temporal sEMG parameters. In conclusion, present study
demonstrated that occurrence frequency is able to provide further information,
besides those supplied by classical temporal sEMG parameters and thus it is
suitable to complement them in the evaluation of variability of myoelectric
activity during walking.
PMID- 28688294
TI - Mother-child discrepancy in perceived parental control and adolescent filial
piety in poor single-mother families.
AB - Based on a sample of 432 poor Chinese single-mother families (mean age of
adolescents = 13.7 years; 51.2% girls; mean age of mothers = 43.5 years) in Hong
Kong, the interaction effect of mother-reported and adolescent-reported maternal
control on filial piety of Chinese adolescents was examined. Results of
polynomial multiple regression analyses showed that the interaction between
mother-reported and adolescent-reported maternal control predicted perceived
filial piety in adolescents. At high levels of mother-reported maternal control,
high adolescent-perceived parental control was associated with higher filial
piety. At low levels of mother-reported maternal control, filial piety increased
initially and then decreased when adolescents reported higher levels of maternal
control. Using multiple group analyses, these associations were found to be
stable across gender and age. The present findings provide insights on how
congruencies and discrepancies between mother-reported and adolescent-reported
maternal control predict filial piety of Chinese adolescents growing up in poor
single-mother families.
PMID- 28688295
TI - Contingency Management interventions for non-prescribed drug use during treatment
for opiate addiction: A systematic review and meta-analysis.
AB - BACKGROUND AND AIMS: Use of non-prescribed drugs during treatment for opiate
addiction reduces treatment success, creating a need for effective interventions.
This review aimed to assess the efficacy of contingency management, a behavioural
treatment that uses rewards to encourage desired behaviours, for treating non
prescribed drug use during opiate addiction treatment. METHODS: A systematic
search of the databases Embase, PsychInfo, PsychArticles and Medline from
inception to March 2015 was performed. Random effects meta-analysis tested the
use of contingency management to treat the use of drugs during opiate addiction
treatment, using either longest duration of abstinence (LDA) or percentage of
negative samples (PNS). Random effects moderator analyses were performed for six
potential moderators: drug targeted for intervention, decade in which the study
was carried out, study quality, intervention duration, type of reinforcer, and
form of opiate treatment. RESULTS: The search returned 3860 papers; 22 studies
met inclusion criteria and were meta-analysed. Follow-up data was only available
for three studies, so all analyses used end of treatment data. Contingency
management performed significantly better than control in reducing drug use
measured using LDA (d=0.57, 95% CI: 0.42-0.72) or PNS (d=0.41) (95% CI: 0.28
0.54). This was true for all drugs other than opiates. The only significant
moderator was drug targeted (LDA: Q=10.75, p=0.03). CONCLUSION: Contingency
management appears to be efficacious for treating most drug use during treatment
for opiate addiction. Further research is required to ascertain the full effects
of moderating variables, and longer term effects.
PMID- 28688296
TI - Effects of ibudilast on oxycodone-induced analgesia and subjective effects in
opioid-dependent volunteers.
AB - Opioid-induced glial activation is hypothesized to contribute to the development
of tolerance to opioid-induced analgesia. This inpatient, double-blind, placebo
controlled, within-subject and between-groups pilot study investigated the dose
dependent effects of ibudilast, a glial cell modulator, on oxycodone-induced
analgesia. Opioid-dependent volunteers were maintained on morphine (30mg, PO,
QID) for two weeks and received placebo ibudilast (0mg, PO, BID) during the 1st
week (days 1-7). On day 8, participants (N=10/group) were randomized to receive
ibudilast (20 or 40mg, PO, BID) or placebo for the remainder of the study. On
days 4 (week 1) and 11 (week 2), the analgesic, subjective, and physiological
effects of oxycodone (0, 25, 50mg/70kg, PO) were determined. Analgesia was
measured using the cold pressor test; participants immersed their hand in cold
water (4 degrees C) and pain threshold and pain tolerability were recorded.
Oxycodone decreased pain threshold and tolerability in all groups during week 1.
During week 2, the placebo group exhibited a blunted analgesic response to
oxycodone for pain threshold and subjective pain ratings, whereas the 40mg BID
ibudilast group exhibited greater analgesia as measured by subjective pain
ratings (p<=0.05). Oxycodone also increased subjective drug effect ratings
associated with abuse liability in all groups during week 1 (p<=0.05); ibudilast
did not consistently affect these ratings. These findings suggest that ibudilast
may enhance opioid-induced analgesia. Investigating higher ibudilast doses may
establish the utility of pharmacological modulation of glial activity to maximize
the clinical use of opioids.
PMID- 28688297
TI - Extended biotic ligand model for predicting combined Cu-Zn toxicity to wheat
(Triticum aestivum L.): Incorporating the effects of concentration ratio, major
cations and pH.
AB - Current risk assessment models for metals such as the biotic ligand model (BLM)
are usually applied to individual metals, yet toxic metals are rarely found
singly in the environment. In the present research, the toxicity of Cu and Zn
alone and together were studied in wheat (Triticum aestivum L.) using different
Ca2+ and Mg2+ concentrations, pH levels and Zn:Cu concentration ratios. The aim
of the study was to better understand the toxicity effects of these two metals
using BLMs and toxic units (TUs) from single and combined metal toxicity data.
The results of single-metal toxicity tests showed that toxicity of Cu and Zn
tended to decrease with increasing Ca2+ or Mg2+ concentrations, and that the
effects of pH on Cu and Zn toxicity were related not only to free Cu2+ and Zn2+
activity, respectively, but also to other inorganic metal complex species. For
the metal mixture, Cu-Zn interactions based on free ion activities were primarily
additive for the different Ca2+ and Mg2+ concentrations and levels of pH. The
toxicity data of individual metals derived by the BLM, which incorporated Ca2+
and Mg2+ competition and toxicity of inorganic metal complexes in a single-metal
toxicity assessment, could predict the combined toxicity as a function of TU.
There was good performance between the predicted and observed effects (root mean
square error [RMSE] = 7.15, R2 = 0.97) compared to that using a TU method with a
model based on free ion activity (RMSE = 14.29, R2 = 0.86). The overall findings
indicated that bioavailability models that include those biochemistry processes
may accurately predict the toxicity of metal mixtures.
PMID- 28688298
TI - Maternal transfer of mercury to songbird eggs.
AB - We evaluated the maternal transfer of mercury to eggs in songbirds, determined
whether this relationship differed between songbird species, and developed
equations for predicting mercury concentrations in eggs from maternal blood. We
sampled blood and feathers from 44 house wren (Troglodytes aedon) and 34 tree
swallow (Tachycineta bicolor) mothers and collected their full clutches (n = 476
eggs) within 3 days of clutch completion. Additionally, we sampled blood and
feathers from 53 tree swallow mothers and randomly collected one egg from their
clutches (n = 53 eggs) during mid to late incubation (6-10 days incubated) to
evaluate whether the relationship varied with the timing of sampling the mother's
blood. Mercury concentrations in eggs were positively correlated with mercury
concentrations in maternal blood sampled at (1) the time of clutch completion for
both house wrens (R2 = 0.97) and tree swallows (R2 = 0.97) and (2) during mid to
late incubation for tree swallows (R2 = 0.71). The relationship between mercury
concentrations in eggs and maternal blood did not differ with the stage of
incubation when maternal blood was sampled. Importantly, the proportion of
mercury transferred from mothers to their eggs decreased substantially with
increasing blood mercury concentrations in tree swallows, but increased slightly
with increasing blood mercury concentrations in house wrens. Additionally, the
proportion of mercury transferred to eggs at the same maternal blood mercury
concentration differed between species. Specifically, tree swallow mothers
transferred 17%-107% more mercury to their eggs than house wren mothers over the
observed mercury concentrations in maternal blood (0.15-1.92 MUg/g ww). In
contrast, mercury concentrations in eggs were not correlated with those in
maternal feathers and, likewise, mercury concentrations in maternal blood were
not correlated with those in feathers (all R2 < 0.01). We provide equations to
translate mercury concentrations from maternal blood to eggs (and vice versa),
which should facilitate comparisons among studies and help integrate toxicity
benchmarks into a common tissue.
PMID- 28688299
TI - Vertical and horizontal assemblage patterns of bacterial communities in a
eutrophic river receiving domestic wastewater in southeast China.
AB - Bacterial communities in rivers receiving untreated domestic wastewater may show
specific spatial assemblage patterns due to a wide range of physicochemical
conditions created by periodic algal bloom. However, there are significant gaps
in understanding environmental forces that drive changes in microbial assemblages
in polluted rivers. In this study, we applied high-throughput sequencing of 16S
rRNA gene amplicons to perform comprehensive spatio-temporal profiling of
bacterial community structure in a local river segment receiving domestic
wastewater discharge in southeast China. Multivariate statistics were then used
to analyse links between bacterial community structure and environmental factors.
Non-metric multidimensional scaling (NMDS) plots showed that the bacterial
community structure was different between upstream and downstream sections of the
river. While the upstream water contained a high proportion of bacteria degrading
xenobiotic aromatic compounds, the downstream water experiencing stronger algal
bloom had a more diverse bacterial community which included the genus Aeromonas
comprising 14 species, most of which are human pathogens. Least discriminant
analysis (LDA) effect size revealed that the surface water was mainly inhabited
by aerobic microorganisms capable of degrading aromatic compounds, and also
contained bacterial genera including pathogenic species. In contrast, in the
bottom water we found, along with aromatic compound-degrading species, anaerobic
denitrifiers and Fe3+-reducing and fermentative bacteria. Variance partitioning
canonical correspondence analysis (VPA) showed that nutrient ratios had a
stronger contribution to bacterial dissimilarities than other major
physicochemical factors (temperature, pH, dissolved oxygen, total organic carbon,
and chlorophyll a). These results show that microbial communities in rivers
continuously receiving domestic wastewater have specific longitudinal and
vertical assemblage patterns and may contain pathogenic species presenting a high
threat to public health. These factors should be taken into consideration while
developing pollution management strategies.
PMID- 28688300
TI - Herbicide and insect resistant Bt cotton pollen assessment finds no detrimental
effects on adult honey bees.
AB - One important concern regarding the use of transgenic cotton expressing
insecticidal toxins from the bacterium Bacillus thuringiensis (Bt) is its
potential detrimental effect on non-target organisms. The honey bee (Apis
mellifera) is the most important pollinator species worldwide and it is directly
exposed to transgenic crops by the consumption of genetically modified (GM)
pollen. However, the potential effects of Bt cotton on A. mellifera remain
unclear. In the present study, we assessed the effects of two Bt cotton
varieties; ZMSJ expressing the Cry1Ac and Cry2Ab insecticidal proteins, and
ZMKCKC producing Cry1Ac and EPSPS, on A. mellifera. Feeding on pollen from two Bt
cotton varieties led to detection of low levels of Cry toxins (<10 ng/g fresh
weight) in the midgut of A. mellifera adults, yet expression of detoxification
genes did not change significantly compared to feeding on non-Bt cotton. Binding
assays showed no Cry1Ac or Cry2Ab binding to midgut brush border membrane
proteins from A. mellifera adults. Taken together, these results support minimal
risk for potential negative effects on A. mellifera by exposure to Bt cotton.
PMID- 28688301
TI - Field location and player roles as constraints on emergent 1-vs-1 interpersonal
patterns of play in football.
AB - This study examined effects of player roles on interpersonal patterns of
coordination that sustain decision-making in 1-vs-1 sub-phases of football in
different field locations near the goal (left-, middle- and right zone).
Participants were fifteen U-16yrs players from a local competitive amateur team.
To measure interpersonal patterns of coordination in the 1-vs-1 dyads we
recorded: (i) the relative distance value between each attacker and defender to
the centre of the goal, and (ii), the relative angle between the centre of the
goal, each defender and attacker. Results revealed how variations in field
locations near the goal (left-, middle- and right-zones) constrained the relative
distance and relative angle values that emerged between them and the goal. It
reveals that relative position of the goal is a key informational variable that
sustained participants' behaviours for dribbling and shooting. Higher values of
relative distance and angle were observed in the middle zone, compared to other
zones. Players' roles also constitute a constraint on the interpersonal
coordination for dribbling and shooting. Additionally, it seems that players'
foot preference constrains the dynamics of interpersonal patterns of coordination
between participants, especially in left and right zones. The findings suggest
that to increase participants' opportunities for action, coaches should account
with field positions, players' roles and preference foot.
PMID- 28688302
TI - Effects of gait speed on the body's center of mass motion relative to the center
of pressure during over-ground walking.
AB - Preferred walking speed (PWS) reflects the integrated performance of the relevant
physiological sub-systems, including energy expenditure. It remains unclear
whether the PWS during over-ground walking is chosen to optimize one's balance
control because studies on the effects of speed on the body's balance control
have been limited. The current study aimed to bridge the gap by quantifying the
effects of the walking speed on the body's center of mass (COM) motion relative
to the center of pressure (COP) in terms of the changes and directness of the COM
COP inclination angle (IA) and its rate of change (RCIA). Data of the COM and COP
were measured from fifteen young healthy males at three walking speeds including
PWS using a motion capture system. The values of IAs and RCIAs at key gait events
and their average values over gait phases were compared between speeds using one
way repeated measures ANOVA. With increasing walking speed, most of the IA and
RCIA related variables were significantly increased (p<0.05) but not for those of
the frontal IA. Significant quadratic trends (p<0.05) with highest directness at
PWS were found in IA during single-limb support, and in RCIA during single-limb
and double-limb support. The results suggest that walking at PWS corresponded to
the COM-COP control maximizing the directness of the RCIAs over the gait cycle, a
compromise between the effects of walking speed and the speed of weight transfer.
The data of IA and RCIA at PWS may be used in future assessment of balance
control ability in people with different levels of balance impairments.
PMID- 28688303
TI - Effect of styrene exposure on plasma parameters, molecular mechanisms and gene
expression in rat model islet cells.
AB - Styrene is an aromatic hydrocarbon compound present in the environment and have
primary exposure through plastic industry. The current study was designed to
evaluate styrene-induced toxicity parameters in rat plasma fasting blood glucose
(FBG) level, oral glucose tolerance, insulin secretion, oxidative stress, and
inflammatory cytokines in cellular and molecular levels. Styrene was dissolved in
corn oil and administered at different doses (250, 500, 1000, 1500, 2000mg/kg/day
and control) to each rat, for 42days. In treated groups, styrene significantly
increased fasting blood glucose, plasma insulin (p<0.001) and glucose tolerance.
Glucose tolerance, insulin resistance and hyperglycemia were found to be the main
consequences correlating gene expression of islet cells. Styrene caused a
significant enhancement of oxidative stress markers (p<0.001) and inflammatory
cytokines in a dose and concentration-dependent manner in plasma (p<0.001).
Moreover, the activities of caspase-3 and -9 of the islet cells were
significantly up-regulated by this compound at 1500 and 2000mg/kg/day styrene
administrated groups (p<0.001). The relative fold change of GLUD1 was
downregulated (p<0.05) and upregulated at 1500 and 2000mg/kg, respectively
(p<0.01). The relative fold changes of GLUT2 were down regulated at 250 and
1000mg/kg and up regulated in 500, 1500 and 2000mg/kg doses of styrene (p<0.01).
The expression level of GCK indicated a significant upregulation at 250mg/kg and
downregulation of relative fold changes in the remaining doses of styrene, except
for no change at 2000mg/kg of styrene for GCK. Targeting genes (GLUD1, GLUT2 and
GCK) of the pancreatic islet cells in styrene exposed groups, disrupted
gluconeogenesis, glycogenolysis pathways and insulin secretory functions. The
present study illustrated that fasting blood glucose, insulin pathway, oxidative
balance, inflammatory cytokines, cell viability and responsible genes of glucose
metabolism are susceptible to styrene, which consequently lead to other
abnormalities in various organs.
PMID- 28688304
TI - Dietary exposure assessment of Chinese population to tetrabromobisphenol-A,
hexabromocyclododecane and decabrominated diphenyl ether: Results of the 5th
Chinese Total Diet Study.
AB - Based on the 5th Chinese Total Diet Study (TDS) carried out in 2011, the dietary
exposure of Chinese population to three currently used brominated flame
retardants (BFRs), tetrabromobisphenol A (TBBPA), hexabromocyclododecane (HBCD)
and decabrominated diphenyl ether (BDE-209), was estimated and the related health
risks were assessed. Levels of the three BFRs were determined in 80 composite
samples from four animal-origin food groups. The average levels of BFRs in
various food groups ranged from 0.671 to 5.76 ng/g lipid weight (lw). The levels
of TBBPA were lower than those of HBCD but higher than those of BDE-209.
Moreover, average contamination levels of TBBPA and HBCD in TDS 2011 were found
to be 3 to 30 times higher than those observed in TDS 2007 in the four food
groups, indicating an increase in TBBPA and HBCD in the environment during 2007
2011. The average estimated daily intakes (EDIs) of TBBPA, HBCD and BDE-209 via
food consumption for a "standard Chinese man" were 1.34, 1.51 and 0.96 ng/kg
bw/day, respectively. Meat and meat products were found to be the major
contributor to the daily dietary intake because the consumption of meat and meat
products were significantly higher than that of other food groups in China. In
comparison, the levels and EDIs of BFRs in this study were found to be higher
than those in most studies worldwide. However, the large margin of exposure
(MOE), with at least 1.1 * 105 calculated following the European Food Safety
Authority (EFSA) approach, indicates that the estimated dietary exposure to these
three BFRs is unlikely to raise significant health concerns. In addition, a
comparison between the contamination levels of TBBPA, HBCD, BDE-209 and some
novel BFRs in food samples from TDS 2011 indicated an obvious shift in the
industrial production and usage pattern between PBDE and non-PBDE BFRs in China.
PMID- 28688305
TI - Accumulation and distribution of organophosphate flame retardants (PFRs) and
their di-alkyl phosphates (DAPs) metabolites in different freshwater fish from
locations around Beijing, China.
AB - Organophosphate flame retardants (PFRs) can be rapidly metabolized in the body,
and recent studies have shown that the di-alkyl phosphates (DAPs) are important
metabolites. The accumulation and distribution of 8 PFRs and their 4 DAPs
metabolites were first investigated in whole-body samples and various tissues of
three freshwater fish species (topmouth gudgeon, crucian carp and loach) with
different feeding habits from locations around Beijing, China. Concentrations of
SigmaPFRs in whole-body samples across all sampling locations ranged from 264.7
to 1973 ng g-1 lipid weight (lw), while all the paired DAP metabolites were
detected in the total range from 35.3 to 510 ng g-1 lw. The calculated log
bioconcentration factors (BCFs) of PFRs in whole fish were correlated with their
log KOW (P < 0.05). The metabolite/parent ratios (MPRs) of SigmaDAPs were
calculated and ranged from 0.10 to 1.12 in whole-fish of all species. The MPRs of
BBOEP/TBOEP were the highest. With respect to their distribution in different
tissues, both the parent PFRs and metabolites were found at relatively higher
levels in the liver than in other tissues (muscle, intestine, kidney and ovary),
which was markedly different from those observed in avian species in previous
studies. The accumulation of PFRs and DAPs in various tissues was not
significantly correlated with the lipid content. The highest PFRs level in the
liver may be related to the active hepatic accumulation processes. Meanwhile, the
MPRs for all 4 pairs were the highest in the kidney relative to the other
tissues. To the best of our knowledge, this is first study of DAPs in wild
animals, and our study may improve the understanding of the accumulation and
metabolism of PFRs in the body.
PMID- 28688306
TI - Investigating the contribution of shipping emissions to atmospheric PM2.5 using a
combined source apportionment approach.
AB - Many studies have been conducted focusing on the contribution of land emission
sources to PM2.5 in China; however, little attention had been paid to other
contributions, especially the secondary contributions from shipping emissions to
atmospheric PM2.5. In this study, a combined source apportionment approach,
including principle component analysis (PCA) and WRF-CMAQ simulation, was applied
to identify both primary and secondary contributions from ships to atmospheric
PM2.5. An intensive PM2.5 observation was conducted from April 2014 to January
2015 in Qinhuangdao, which was close to the largest energy output port of China.
The chemical components analysis results showed that the primary component was
the major contributor to PM2.5, with proportions of 48.3%, 48.9%, 55.1% and 55.4%
in spring, summer, autumn and winter, respectively. The secondary component
contributed higher fractions in summer (48.2%) and winter (36.8%), but had lower
percentages in spring (30.1%) and autumn (32.7%). The hybrid source apportionment
results indicated that the secondary contribution (SC) of shipping emissions to
PM2.5 could not be ignored. The annual average SC was 2.7%, which was comparable
to the primary contribution (2.9%). The SC was higher in summer (5.3%), but lower
in winter (1.1%). The primary contributions to atmospheric PM2.5 were 3.0%, 2.5%,
3.4% and 2.7% in spring, summer, autumn and winter, respectively. As for the
detailed chemical components, the contributions of shipping emissions were 2.3%,
0.5%, 0.1%, 1.0%, 1.7% and 0.1% to elements & sea salt, primary organic aerosol
(POA), element carbon (EC), nitrate, sulfate and secondary organic carbon (SOA),
respectively. The results of this study will further the understanding of the
implications of shipping emissions in PM2.5 pollution.
PMID- 28688307
TI - The current situation of inorganic elements in marine turtles: A general review
and meta-analysis.
AB - Inorganic elements (Pb, Cd, Hg, Al, As, Cr, Cu, Fe, Mn, Ni, Se and Zn) are
present globally in aquatic systems and their potential transfer to marine
turtles can be a serious threat to their health status. The environmental fate of
these contaminants may be traced by the analysis of turtle tissues. Loggerhead
turtles (Caretta caretta) are the most frequently investigated of all the sea
turtle species with regards to inorganic elements, followed by Green turtles
(Chelonia mydas); all the other species have considerably fewer studies.
Literature shows that blood, liver, kidney and muscle are the tissues most
frequently used for the quantification of inorganic elements, with Pb, Cd, Cu and
Zn being the most studied elements. Chelonia mydas showed the highest
concentrations of Cr in muscle (4.8 +/- 0.12), Cu in liver (37 +/- 7) and Mg in
kidney (17 MUg g-1 ww), Cr and Cu from the Gulf of Mexico and Mg from Japanese
coasts; Lepidochelys olivacea presented the highest concentrations of Pb in blood
(4.46 5) and Cd in kidney (150 +/- 110 MUg g-1 ww), both from the Mexican
Pacific; Caretta caretta from the Mediterranean Egyptian coast had the highest
report of Hg in blood (0.66 +/- 0.13 MUg g-1 ww); and Eretmochelys imbricata from
Japan had the highest concentration of As in muscle (30 +/- 13 13 MUg g-1 ww).
The meta-analysis allows us to examine some features that were not visible when
data was analyzed alone. For instance, Leatherbacks show a unique pattern of
concentration compared to other species. Additionally, contamination of different
tissues shows some tendencies independent of the species with liver and kidney on
one side and bone on the other being different from other tissues. This review
provides a general perspective on the accumulation and distribution of these
inorganic elements alongside existing information for the 7 sea turtle species.
PMID- 28688308
TI - A PCR-free electrochemical method for messenger RNA detection in cancer tissue
samples.
AB - Despite having reliable and excellent diagnostic performances, the currently
available messenger RNA (mRNA) detection methods mostly use enzymatic
amplification steps of the target mRNA which is generally affected by the sample
manipulations, amplification bias and longer assay time. This paper reports an
amplification-free electrochemical approach for the sensitive and selective
detection of mRNA using a screen-printed gold electrode (SPE-Au). The target mRNA
is selectively isolated by magnetic separation and adsorbed directly onto an
unmodified SPE-Au. The surface-attached mRNA is then measured by differential
pulse voltammetry (DPV) in the presence of [Fe(CN)6]4-/3- redox system. This
method circumvents the PCR amplification steps as well as simplifies the assay
construction by avoiding multiple steps involved in conventional biosensing
approaches of using recognition and transduction layers. Our method has
demonstrated good sensitivity (LOD = 1.0pM) and reproducibility (% RSD = <5%, for
n = 3) for detecting FAM134B mRNA in two cancer cell lines and a small cohort of
clinical samples (number of samples = 26) collected from patients with
oesophageal cancer. The analytical performance of our method is validated with a
standard qRT-PCR analysis. We believe that our PCR-free approach holds a great
promise for the analysis of tumor-specific mRNA in clinical samples.
PMID- 28688309
TI - Programmable strand displacement-based magnetic separation for simultaneous
amplified detection of multiplex microRNAs by chemiluminescence imaging array.
AB - High throughput analysis of miRNAs is of great significance to clinical and
biomedical applications. In this work, we have developed a highly sensitive and
selective chemiluminescence imaging array (CLIA) for simultaneous detection of
three miRNAs with high throughput, easy operation and low cost. In this assay,
three kinds of hairpins that can specially recognize respective miRNAs (miR-155,
miR-let-7a and miR-141) are parallel modified on the magnetic beads (MBs). The
employment of MBs enables quick sorting of multiplex targets in high yield and
purity with high throughput. Upon introduction of the target miRNAs, they
hybridize to the corresponding hairpins and initiate the DNA machines with the
assistance of Klenow fragment exo- DNA polymerase and Nb.BbvCI NEase, achieving
exponential amplification of targets. After that, the toehold-mediated strand
displacement (TMSD) reactions are performed through sequential addition of
displacement probes under magnetic separation, resulting in the release of HRP
tagged DNA hybrids in solution for CL imaging and recovery of MBs for repetitive
use. This CLIA method demonstrates ultrahigh sensitivity with detection limits
down to fM level, wide linear range over 5 orders of magnitude, excellent
selectivity to distinguish one-base mismatched target miRNA, and good performance
in real sample analysis. Together with the advantages of high throughput, easy
operation, acceptable accuracy, and good recyclability and reproducibility, the
proposed multiplex CLIA method holds great potential in practical applications,
such as profiling the pattern of miRNA expression, disease screening, biomedical
research, and so on.
PMID- 28688310
TI - Viologen-functionalized single-walled carbon nanotubes as carrier nanotags for
electrochemical immunosensing. Application to TGF-beta1 cytokine.
AB - Viologen-SWCNT hybrids are synthesized by aryl-diazonium chemistry in the
presence of isoamyl nitrite followed by condensation reaction of the resulting
HOOC-Phe-SWCNT with 1-(3-aminoethyl)-4,4'-bipyridinium bromine and N-alkylation
with 2-bromoethylamine. The V-Phe-SWCNT hybrids were characterized by using
different spectroscopic techniques (FT-IR, Raman, UV-vis), TGA and Kaiser test.
Viologen-SWCNTs were used for the preparation of an electrochemical immunosensor
for the determination of the transforming growth factor beta1 (TGF-beta1)
cytokine considered as a reliable biomarker in several human diseases. The
methodology involved preparation of V-Phe-SWCNT(-HRP)-anti-TGF conjugates by
covalent linkage of HRP and anti-TGF onto V-Phe-SWCNT hybrids. Biotinylated anti
TGF antibodies were immobilized onto 4-carboxyphenyl-functionalized SPCEs
modified with streptavidin and a sandwich type immunoassay was implemented for
TGF-beta1 with signal amplification using V-Phe-SWCNT(-HRP)-anti-TGF conjugates
as carrier tags. The analytical characteristics exhibited by the as prepared
immunosensor (range of linearity between 2.5 and 1000pgmL-1 TGF-beta1; detection
limit of 0.95pgmL-1) improve notably those reported with other previous
immunosensors or ELISA kits. A great selectivity against other proteins was also
found. The prepared immunosensor was validated by determining TGF-beta1 in real
saliva samples. Minimal sample treatment was required and the obtained results
were in excellent agreement with those obtained by using a commercial ELISA kit.
PMID- 28688311
TI - A novel multifunctional electrochemical platform for simultaneous detection,
elimination, and inactivation of pathogenic bacteria based on the Vancomycin
functionalised AgNPs/3D-ZnO nanorod arrays.
AB - A novel fast, sensitive, and specific multifunctional electrochemical platform
has been proposed for simultaneous detection, elimination, and inactivation of
pathogenic bacteria for the first time. The platform is constituted with three
dimensional ZnO nanorod arrays (3D-ZnO) decorated with sliver nanoparticles
(AgNPs) and functionalized with vancomycin (Van). Based on the specific
recognition of Van for Gram-positive bacteria, the fabricated electrochemical
platform has presented high detection sensitivity to Staphylococcus aureus with a
low detection limit of 330cfu/mL and adaptable bacterial-elimination efficiency
(50%) at low concentrations (1000-2000cfu/mL). Moreover, the platform has shown
high antibacterial activity (99.99%) arising from the synergistic germicidal
effect of the composited antibacterial AgNPs and Van units. The current work
could provide new strategies to construct advanced platforms for simultaneous
detection, elimination, and inactivation of various pathogenic bacteria.
PMID- 28688312
TI - Total proximal anastomosis detachment after classical bentall procedure.
AB - INTRODUCTION: Since its introduction in 1968, the Bentall procedure has been the
primary surgical solution for aneurysms of the aortic root. However, many
surgeons have reported serious procedural complications such as detachment of
coronary ostia and pseudoaneurysm formation at anastomosis sites. Therefore, the
Bentall procedure has undergone several modifications to eliminate those
complications. Partial or total detachment of the proximal anastomosis is rarely
reported. PRESENTATION OF CASE: We report a total detachment of the proximal
anastomosis after a Bentall operation with emphasis on the possible practical
mechanisms, which might have led to the development of this very rare
complication. The diagnosis was confirmed at a routine follow up examination and
urgent surgery was performed. We also report our operative solution and review
other possible surgical solutions that might be considered in this setting.
DISCUSSION: The Bentall procedure and its modifications continue to be considered
the gold standard for treating aneurysms involving the aortic root. Various
modifications can serve as optimal solutions for procedure-related complications.
CONCLUSION: Surgeons performing the Bentall procedure must be familiar with all
existing modifications because they are complementary to the original surgical
procedure. In the absence of endocarditis left ventricle outflow tract elongation
may be an acceptable surgical solution to deal with total detachment of the
proximal anastomosis.
PMID- 28688313
TI - Laparoscopic management of a complicated case of Wilkie's syndrome: A case
report.
AB - INTRODUCTION: Superior mesenteric artery (SMA) syndrome also known as Wilkie's
syndrome is a rare condition caused by the entrapment of the third part of the
duodenum between the aorta and the SMA. The incidence of Wilkie's syndrome range
between 0.013% and 0.3%. The normal angle between the aorta and SMA has been
described to range between 38 degrees and 65 degrees , whereas in Wilkie's
syndrome this angle is reduced to less than 20 degrees causing gastric outlet
obstruction. CASE PRESENTATION: We report a case of a previously diagnosed 43
year-old male with SMA syndrome, whom had been conservatively managed for 5-years
for recurrent admissions with symptoms of gastric outlet obstruction. During his
last admission, CT abdomen demonstrated gastric pneumatosis and portal venous gas
requiring urgent surgical intervention. Duodenojejunostomy was successfully
performed using laparoscopic technique. DISCUSSION: SMA syndrome is thought to
occur secondary to the rapid and excessive weight loss leading to the reduction
of the mesenteric fat around the aorta and SMA, thereby reducing the normal angle
between the two arteries. Conservative medical management is usually the first
line of treatment in uncomplicated cases. Surgical management is usually reserved
only after failed conservative management or complicated cases, at which time
either an open or laparoscopic surgical approach is undertaking. CONCLUSION:
Surgical intervention is the mainstay in complicated cases of SMA syndrome and in
refractory cases to conservative management. Advantages of laparoscopic approach
over open surgery include rapid recovery time, reduced post-operative pain and
shorter hospital stay.
PMID- 28688314
TI - A study of transfer and prevalence of organic gunshot residues.
AB - The main goal of the present study was to determine the amounts and distribution
of organic gunshot residues (OGSR) on the shooter's upper body and clothing after
discharging a pistol. A preliminary study was also performed to evaluate the
prevalence of OGSR in the general population as well as in a police laboratory
environment. In the transfer study, results indicated that OGSR are not only
transferred to the hand of the shooter, but also to other parts of the upper
body. Thus, wrists and forearms also represent interesting targets as they are
washed less frequently than hands. Samples from the face and hair of the shooters
resulted in no OGSR detection just after firing. It was also observed that the
concentrations recovered from clothing are generally higher compared to the same
skin area. Prevalence in both general (n=27) and police populations (n=25) was
low. No OGSR was detected in the samples from the general population and only two
samples from the police population were found positive.
PMID- 28688315
TI - The effect of health on urban-settlement intention of rural-urban migrants in
China.
AB - Previous studies have not paid enough attention to the effect of health on urban
settlement intention of rural-urban migrants in China. Using survey data from the
Rural Urban Migration in China project, this article examines how self-rated
physical and mental health influence rural-urban migrants' intention to settle
down in cities. First, the results show that both self-rated physical and mental
health are significant factors influencing the migrants' intention to permanently
move to cities. Second, the effect of physical health on rural-urban migrants'
intentions to permanently reside in cities can be moderated by their length of
urban residence. Third, the impact of health on rural-urban migrants' urban
settlement intention shows no generational differences. According to the research
findings, this paper discusses how urban-settlement intention of rural-urban
migrants based on health selection might impair urbanization, exacerbate health
disparity between the rural and urban areas, and aggravate the burden on
healthcare system in rural areas of China in the long run.
PMID- 28688316
TI - Cultivating our humanity: A systematic review of care farming & traumatic grief.
AB - Traumatic grief is a complex biopsychosocial experience, frequently (and
contentiously) medicalized in the Western world. Care farming is an increasingly
popular place-based intervention utilizing agricultural settings to care for
vulnerable groups. We sought to establish the extent of care farming in relation
to traumatic grief and query the potential of care farming as an intervention for
this specific population. A systematic review highlights that whilst
understudied, the success of care farming as an intervention for other
populations experiencing psychological distress demonstrates the huge potential
for care farming as a means to therapeutically engage with individuals
experiencing traumatic grief.
PMID- 28688317
TI - Smelling therapeutic landscapes: Embodied encounters within spaces of care
farming.
AB - The conceptual framework of 'therapeutic landscapes' has been used as a means of
considering the significance of specific environments, spaces, and places for
aspects of health. Building on a growing attention to the sensory elements of
spaces of health and wellbeing, this article mobilises empirical research on
'care farming' practices to discuss how smellscapes come to be crucial in
fulfilling anticipations, imaginations, and expectations of a 'therapeutic
space'. This article highlights how embodied relationships with specific scents
can constitute a therapeutic encounter with place, actively influencing practices
and engagement with(in) place, and the ways by which place can have a meaningful
affect on health.
PMID- 28688318
TI - Erratum: Defluoridation of drinking water using a new flow
columnelectrocoagulation reactor (FCER) - Experimental, statistical, and economic
approach.
PMID- 28688319
TI - Study of decolorisation of binary dye mixture by response surface methodology.
AB - Decolorisation of a complex mixture of two different classes of textile dyes
Direct Red 81 (DR81) and Rhodamine B (RHB), simulating one of the most important
condition in real textile effluent was investigated onto deoiled Argemone
Mexicana seeds (A. Mexicana). The adsorption behaviour of DR81 and RHB dyes was
simultaneously analyzed in the mixture using derivative spectrophotometric
method. Central composite design (CCD) was employed for designing the experiments
for this complex binary mixture where significance of important parameters and
possible interactions were analyzed by response surface methodology (RSM).
Maximum adsorption of DR81 and RHB by A. Mexicana was obtained at 53 degrees C
after 63.33 min with 0.1 g of adsorbent and 8 * 10-6 M DR81, 12 * 10-6 M RHB with
composite desirability of 0.99. The predicted values for percentage removal of
dyes from the mixture were in good agreement with the experimental values with R2
> 96% for both the dyes. CCD superimposed RSM confirmed that presence of
different dyes in a solution created a competition for the adsorbent sites and
hence interaction of dyes was one of the most important factor to be studied to
simulate the real effluent. The adsorbent showed remarkable adsorption capacities
for both the dyes in the mixture.
PMID- 28688320
TI - Stabilization of lead in an alkali-activated municipal solid waste incineration
fly ash-Pyrophyllite-based system.
AB - This work focuses on the stabilization and speciation of lead (Pb) in a composite
solid produced from an alkali-activated municipal solid waste incineration fly
ash (MSWIFA)-pyophyllite-based system. The solid product was synthesized after
mixtures of raw materials (dehydrated pyrophyllite, MSWIFA, 14 mol/L aqueous
sodium hydroxide, and sodium silicate solution) were cured at 105 degrees C for
24 h. The product could reduce the leaching of Pb and the Pb concentration in the
leachate was 7.0 * 10-3 using the Japanese leaching test and 9.7 * 10-4 mg/L
using toxicity characteristics leaching procedure method, which satisfied the
respective test criteria and successfully stabilized Pb in this system. The solid
product had a compressive strength of 2 MPa and consisted mainly of crystalline
phases. Scanning electron microscopy with X-ray analysis and X-ray absorption
fine structure suggested that Pb was present along with Al, Si, and O, and that
the atomic environment around the Pb was similar to that of PbSiO3. These results
suggest that the alkali-activated MSWIFA-pyrophyllite-based system could be used
to stabilize Pb in MSWIFA.
PMID- 28688321
TI - In vitro degradation of a 3D porous Pennisetum purpureum/PLA biocomposite
scaffold.
AB - The in vitro degradation and mechanical properties of a 3D porous Pennisetum
purpureum (PP)/polylactic acid (PLA)-based scaffold were investigated. In this
study, composite scaffolds with PP to PLA ratios of 0%, 10%, 20%, and 30% were
immersed in a PBS solution at 37 degrees C for 40 days. Compression tests were
conducted to evaluate the compressive strength and modulus of the scaffolds,
according to ASTM F451-95. The compression strength of the scaffolds was found to
increase from 1.94 to 9.32MPa, while the compressive modulus increased from 1.73
to 5.25MPa as the fillers' content increased from 0wt% to 30wt%. Moreover, field
emission scanning electron microscopy (FESEM) and X-ray diffraction were employed
to observe and analyse the microstructure and fibre-matrix interface.
Interestingly, the degradation rate was reduced for the PLA/PP20 scaffold, though
insignificantly, this could be attributed to the improved mechanical properties
and stronger fibre-matrix interface. Microstructure changes after degradation
were observed using FESEM. The FESEM results indicated that a strong fibre-matrix
interface was formed in the PLA/PP20 scaffold, which reflected the addition of P.
purpureum into PLA decreasing the degradation rate compared to in pure PLA
scaffolds. The results suggest that the P. purpureum/PLA scaffold degradation
rate can be altered and controlled to meet requirements imposed by a given tissue
engineering application.
PMID- 28688322
TI - Blood-based bioenergetic profiling: A readout of systemic bioenergetic capacity
that is related to differences in body composition.
PMID- 28688323
TI - Valorization of algal waste via pyrolysis in a fixed-bed reactor: Production and
characterization of bio-oil and bio-char.
AB - The aim of the present work is to develop processes for the production of bio-oil
and bio-char from algae waste using the pyrolysis at controlled conditions. The
pyrolysis was carried out at different temperatures 400-600 degrees C and
different heating rates 5-50 degrees C/min. The algal waste, bio-oil and bio-char
were successfully characterized using Elemental analysis, Chemical composition,
TGA, FTIR, 1H NMR, GC-MS and SEM. At a temperature of 500 degrees C and a heating
rate of 10 degrees C/min, the maximum yield of bio-oil and bio-char was found to
be 24.10 and 44.01wt%, respectively, which was found to be strongly influenced by
the temperature variation, and weakly affected by the heating rate variation.
Results show that the bio-oil cannot be used as bio-fuel, but can be used as a
source of value-added chemicals. On the other hand, the bio-char is a promising
candidate for solid fuel applications and for the production of carbon materials.
PMID- 28688324
TI - Growing Chlorella vulgaris on thermophilic anaerobic digestion swine manure for
nutrient removal and biomass production.
AB - Liquid swine manure was subjected to thermophilic anaerobic digestion, ammonia
stripping and centrifugation in order to increase the available carbon sources
and decrease the ammonia concentration and turbidity. Chlorella vulgaris (UTEX
2714) was grown on minimally diluted (2*, 3* and 4*) autoclaved and non
autoclaved pretreated anaerobic digestion swine manure (PADSM) in a batch-culture
system for 7days. Results showed that C. vulgaris (UTEX 2714) grew best on 3*
PADSM media, and effectively removed NH4+-N, TN, TP and COD by 98.5-99.8%, 49.2
55.4%, 20.0-29.7%, 31.2-34.0% and 99.8-99.9%, 67.4-70.8%, 49.3-54.4%, 73.6-78.7%
in differently diluted autoclaved and non-autoclaved PADSM, respectively. Results
of chemical compositions indicated that contents of pigment, carbohydrate,
protein and lipid in C. vulgaris (UTEX 2714) changed with the culture conditions.
Moreover, its fatty acid profiles suggested that this alga could be used as
animal feed if cultivated in autoclaved PADSM or as good-quality biodiesel
feedstock if cultivated in non-autoclaved PADSM.
PMID- 28688325
TI - Effect of low temperature of thermal pretreatment on anaerobic digestion of
textile dyeing sludge.
AB - The minimization and methane production of textile dyeing sludge (TDS) can be
simultaneously attained via anaerobic digestion (AD). However, the possible
toxicity and complex recalcitrant organic matters involved in limited the
hydrolysis of TDS. Therefore, the low-temperature of thermal pretreatment (LTTP)
lasting for 1h at temperatures from 60 to 100 degrees C was employed to
accelerate the hydrolysis and subsequent methane generation of TDS. The results
showed that LTTP with temperatures higher than 70 degrees C obviously improve the
AD performance of TDS. Highest accumulative methane production was achieved for
100 degrees C pretreated TDS and from thermal analysis point of view it was due
to the disintegration of some recalcitrant macromolecules in TDS. Nevertheless,
90 degrees C pretreated TDS did not perform favorable methane yield as expected,
attributing to the inhibited acetogenesis as well as the hindered methanogenesis
which was simultaneously competed by dye reducer for electrons.
PMID- 28688326
TI - Metabolic peculiarities of the citric acid overproduction from glucose in yeasts
Yarrowia lipolytica.
AB - Comparative study of 43 natural yeast strains belonging to 20 species for their
capability for overproduction of citric acid (CA) from glucose under nitrogen
limitation of cell growth was carried out. As a result, natural strain Yarrowia
lipolytica VKM Y-2373 was selected. The effect of growth limitation by biogenic
macroelements (nitrogen, phosphorus, or sulfur) on the CA production by the
selected strain was studied. It was shown that yeasts Y. lipolytica grown under
deficiency of nitrogen, phosphorus, or sulfur were able to excrete CA in
industrially sufficient amounts (80-85g/L with the product yield (YCA) of 0.70
0.75g/g and the process selectivity of 92.5-95.3%). Based on the obtained data on
activities of enzymes involved in the initial stages of glucose oxidation, the
cycle of tricarboxylic acids, and the glyoxylate cycle, the conception of the
mechanism responsible for the CA overproduction from glucose in Y. lipolytica was
formulated.
PMID- 28688327
TI - CO2 capture from air by Chlorella vulgaris microalgae in an airlift
photobioreactor.
AB - In this work, hydrodynamics and CO2 biofixation study was conducted in an airlift
bioreactor at the temperature of 30+/-2 degrees C. The main objective of this
work was to investigate the effect of high gas superficial velocity on CO2
biofixation using Chlorella vulgaris microalgae and its growth. The study showed
that Chlorella vulgaris in high input gas superficial velocity also had the
ability to grow and remove the CO2 by less than 80% efficiency.
PMID- 28688328
TI - Synthesis of 1,3-dioleoyl-2-arachidonoylglycerol-rich structured lipids by lipase
catalyzed acidolysis of microbial oil from Mortierella alpina.
AB - Microbial oils (MOs) have gained widespread attention due to their functional
lipids and health promoting properties. In this study, 1,3-dioleoyl-2
arachidonoylglycerol-rich structured lipids (SLs) were produced from MO and oleic
acid (OA) via solvent-free acidolysis catalyzed by Lipozyme RM IM. Under the
optimal conditions, the content of unsaturated fatty acids (UFAs) increased from
60.63 to 84.00%, while the saturated fatty acids (SFAs) content decreased from
39.37 to 16.00% at sn-1,3 positions in SLs. Compared with MO, arachidonic acid
(ARA) content at the sn-2 position of SLs accounted for 49.71%, whereas OA was
predominantly located at sn-1,3 positions (47.05%). Meanwhile, the most abundant
triacylglycerol (TAG) species in SLs were (18:1-20:4-18:1), (20:4-20:4-18:1),
(18:1-18:2-18:1), (18:1-18:2-18:0) and (24:0-20:4-18:1) with a relative content
of 18.79%, 11.94%, 6.07%, 5.75% and 4.84%, respectively. Such novel SLs with
improved functional properties enriched with UFAs are highly desirable and have
the potential to be used in infant formula.
PMID- 28688329
TI - The role of inoculum's origin on the methane yield of different substrates in
biochemical methane potential (BMP) tests.
AB - The impact of the inoculum's origin on the methane yield in Biochemical Methane
Potential (BMP) tests was investigated. The three most commonly applied inocula
were chosen, originating from (i) a digester of a wastewater treatment plant,
(ii) an agricultural biogas plant treating manure and energy crops, and (iii) a
biowaste treatment plant. The performance of each inoculum was tested with four
different substrates, namely sewage sludge, dried whole crop maize, food waste,
and microcrystalline cellulose as a typical reference material. The results
revealed that the choice of inoculum had no significant impact on the specific
methane yield of the tested substrates except for cellulose. Still, the specific
methane production rate was significantly influenced by the choice of the
inoculum especially for sewage sludge, but also for food waste and cellulose,
whereas it became clear that an inoculum adapted to a substrate is beneficial for
a speedy digestion.
PMID- 28688330
TI - Low-energy biomass pretreatment with deep eutectic solvents for bio-butanol
production.
AB - Waste lettuce leaves - from the "fresh cut vegetable" industry - were pretreated
with the deep eutectic solvent (DES) made of choline chloride - glycerol.
Reaction time (3-16h) and the operation temperature (80-150 degrees C) were
investigated. Enzymatic glucose and xylose yields of 94.9% and 75.0%,
respectively were obtained when the biomass was pretreated at 150 degrees C for
16h. Sugars contained in the biomass hydrolysate were fermented in batch cultures
of Clostridium acetobutylicum DSMZ 792. The energy consumption and the energy
efficiency related to the DES pretreatment were calculated and compared to the
most common lignocellulosic pretreatment processes reported in the literature.
The DES pretreatment process was characterized by lower energy required (about
28% decrease and 72% decrease) than the NAOH pretreatment and steam explosion
process respectively. The Net Energy Ratio (NER) value related to butanol
production via DES biomass pretreatment was assessed.
PMID- 28688331
TI - IDEAL framework in surgical innovation applied on laparoscopic niche repair.
AB - The research objective of the current systematic literature review is to classify
the laparoscopic niche repair according to the IDEAL framework of 'innovation
stages' and to recommend the required research setting to facilitate safe and
properly timed implementation of the technique. In doing so, we are also able to
evaluate the practical applicability of the IDEAL framework. A systematic search
of the available literature on laparoscopic niche repair was performed in PubMed,
Embase, and the Wiley/Cochrane library. Articles were classified according to the
IDEAL framework and recommendations were given on additional required research
before the technique can be safely implemented. Practical applicability of the
IDEAL framework was also evaluated. Introduction of laparoscopic niche repair
matches Idea (1) and Development (2a), according to the stages of IDEAL
framework, although most studies are retrospective and complications have not
been registered structurally in a considerable number of the articles. As
feasibility and safety have been more or less established and surgery has been
further developed we enter stage 2b (Exploration) and need prospective trials
preferably comparing the effectiveness of laparoscopic niche repair to expectant
management, the current standard care. Available studies were classified with the
use of the IDEAL framework, achieving an overall IDEAL stage to be 2a
Development. As clinical outcomes, though poorly registered, have been
substantially improved, laparoscopic niche repair needs to be carried forward by
more advanced study designs.
PMID- 28688332
TI - Regenerative capacity of allogenic gingival margin- derived stem cells with
fibrin glue on albino rats' partially dissected submandibular salivary glands.
AB - OBJECTIVE: To evaluate the possible regenerative effect of allogenic gingival
margin-derived stem cells (GMSCs) with or without autologous fibrin glue on
partially dissected submandibular salivary glands of albino rats. METHODS: Forty
rats were randomly divided into four equal groups. Group I, where no operation
was performed, was considered the negative control. Group II rats were considered
the positive control and were subjected to a rectangular cut on the outer surface
of the center right of the submandibular salivary gland and received no other
treatment. Groups III and IV rats were handled as those in group II, but the cut
areas of group III were filled with fibrin glue and the cut borders of group IV
were injected with 1*105cell/ml GMSCs and then glued with fibrin glue. Five
animals from each group were euthanized at the end of the first postoperative
week, while the remaining animals were euthanized at the end of the second
postoperative week, i.e., end of the experiment. RESULTS: Regeneration of ductal,
acinar, and myoepithelial cells was better in group IV. A two-way ANOVA for
proliferating cell nuclear antigen and alpha-smooth muscle actin revealed an
overall significant difference between the different groups (P<0.05). In
addition, an LSD post hoc test for multiple comparisons revealed a significant
difference between each two groups. An independent sample t-test revealed
significant differences between time periods for groups II, III, and IV, but
there were no significant differences between the time periods for group I.
CONCLUSION: Injecting GMSCs at the cut borders and gluing the cut area with
autologous fibrin glue ameliorates the regeneration of partially dissected
submandibular salivary gland better than using fibrin glue alone.
PMID- 28688333
TI - Toxoplasmosis accelerates acquisition of epilepsy in rats undergoing chemical
kindling.
AB - Epilepsy is one of the most common neurologic disorders worldwide with no
distinguishable cause in 60% of patients. One-third of the world population has
been infected with Toxoplasma gondii. This intracellular parasite has high
tropism for excitable cells including neurons. We assessed impact of acute and
chronic T. gondii infection on epileptogenesis in pentylenetetrazole (PTZ)
kindling model in male rats. T. gondii cysts were administered to rats by
intraperitoneal (i.p.) injection. The presence of T. gondii cysts in the brain of
rats was verified by hematoxylin-eosin staining. One and eight weeks after cysts
injection, as acute and chronic phases of infection, PTZ (30mg/kg, i.p.) was
injected to the rats every other day until manifestation of generalized seizures.
Histologic findings confirmed cerebral toxoplasmosis in rats. The rats with acute
or chronic Toxoplasma infection became kindled by lower number of PTZ injections
(14.8+/-1 and 13.6+/-1 injections, respectively) compared to corresponding
uninfected rats (18.7+/-1 and 16.9+/-1 injections, p<0.05). Toxoplasma infection
increased the rate of kindling in rats. The chronically-infected rats achieved
focal and also generalized seizures earlier than the rats with acute infection.
Toxoplasmosis might be considered as a risk factor for acquisition of epilepsy.
PMID- 28688335
TI - The fluorescent property of 3-[(2-hydroxy-1-naphthyl) methylideneamino]benzoic
acid and its application as fluorescent chemosensor for Hg2+ and Al3+ ions.
AB - This manuscript studies the fluorescent property of 3-[(2-hydroxy-1
naphthyl)methylideneamino]benzoic acid (H2L). Fluorescent spectra show that in
different solvents, H2L displays different fluorescent properties, which can be
attributed to the interaction between the solvents and H2L. Further study
indicates that H2L exhibits a highly selective and sensitive recognition for Hg2+
ions in dimethylsulfoxide (DMSO), Al3+ ions in methanol and N,N'
dimethylformamide/water (DMF/H2O, 1/1, v/v). The bonding modes and bonding ratio
of H2L and metal ions in different solvents are explored by Job's plot, 1H NMR
titration, and electrospray ionization mass spectrometry (ESI-MS). The probable
mechanisms were discussed.
PMID- 28688334
TI - "Behind Closed Doors with open minds?": A qualitative study exploring nursing
home staff's narratives towards their roles and duties within the context of
sexuality in dementia.
AB - BACKGROUND: Despite sexual expression being recognised as a fundamental human
need, sexuality in old age is often ignored and frequently misunderstood, with
residents with dementia in a nursing home often viewed as asexual or incapable of
being sexually active. OBJECTIVES: The current study aims to understand the views
held by nursing care home staff towards dementia and sexuality and explore the
roles they may adopt whilst responding and managing sexual needs and expression
for residents with dementia. METHODS: Face to face, in-depth, semi structured
interviews were conducted with eight staff members working in two nursing homes
in Greater London, United Kingdom. Data were analysed using Interpretative
Phenomenological Analysis. RESULTS: The findings suggest that representations of
sexuality in dementia held by nursing home staff ranged from the perception that
sexual expression in old age was part of human nature and a basic human right to
others that proposed that with the loss of memory, people with dementia may also
experience loss of interest in sexuality and intimacy. Based on the
representation of sexuality held (personhood versus biomedical model), nursing
home staff adopted a role or a combination of roles (a facilitator, an informant,
a distractor, an empathiser, a safeguarder) that legitimised past and anticipated
responses in managing sexual expression in the nursing home setting. Nursing home
staff's responses varied depending on the severity of the condition, level of
involvement of the resident's family and their own personal views on their duty
of care, old age, sexuality and dementia. CONCLUSION: The simplified binary
labelling and classification of sexual behaviour in dementia as appropriate or
inappropriate often applied in institutional settings, fails to account for
complex factors that may influence staff's decisions on the ethical dilemmas
raised by dementia. A role based continuum approach could help staff move away
from rigid binary judgments and train them to adopt formal carer roles that
promote a more contextualised rights based approach in the provision of dementia
care.
PMID- 28688336
TI - The biochemical, nanomechanical and chemometric signatures of brain cancer.
AB - Raman spectroscopy and imaging combined with AFM topography and mechanical
indentation by AFM have been shown to be an effective tool for analysis and
discrimination of human brain tumors from normal structures. Raman methods have
potential to be applied in clinical practice as they allow for identification of
tumor margins during surgery. In this study, we investigate medulloblastoma
(grade IV WHO) (n=5) and the tissue from the negative margins used as normal
controls. We compare a high grade medulloblastoma (IV grade), and non-tumor
samples from human central nervous system (CNS) tissue. Based on the properties
of the Raman vibrational spectra and Raman images we provide a real-time feedback
that is label-free method to monitor tumor metabolism that reveals reprogramming
of biosynthesis of lipids, and proteins. We have found that the high-grade tumors
of central nervous system (medulloblastoma) exhibit enhanced level of beta-sheet
conformation and down-regulated level of alpha-helix conformation when comparing
against normal tissue. We have shown that the ratio of Raman intensities
I2930/I2845 at 2930 and 2845cm-1 is a good source of information on the ratio of
lipid and protein contents. We have found that the ratio reflects the lipid and
protein contents of tumorous brain tissue compared to the non-tumor tissue.
Almost all brain tumors have the Raman intensity ratios significantly higher
(1.99+/-0.026) than that found in non-tumor brain tissue, which is 1.456+/-0.02,
and indicates that the relative amount of lipids compared to proteins is
significantly higher in the normal brain tissue. Mechanical indentation using AFM
on sliced human brain tissues (medulloblastoma, grade IV) revealed that the
mechanical properties of this tissue are strongly heterogeneous, between 1.8 and
75.7kPa, and the mean of 27.16kPa. The sensitivity and specificity obtained
directly from PLSDA and cross validation gives a sensitivity and specificity of
98.5% and 96% and 96.3% and 92% for cross-validation, respectively. The high
sensitivity and specificity demonstrates usefulness for a proper decision for a
Raman diagnostic test on biochemical alterations monitored by Raman spectroscopy
related to brain cancer development.
PMID- 28688337
TI - Associations between cognition and serotonin receptor 1B binding in patients with
major depressive disorder - A pilot study.
PMID- 28688338
TI - Pregnenolone as an adjunct to risperidone for treatment of women with
schizophrenia: A randomized double-blind placebo-controlled clinical trial.
AB - There have been few studies of pregnenolone therapy in schizophrenia and those
that exist have been subject to several critical limitations, thus yielding
inconsistent results. We attempted to assess the therapeutic effect of
pregnenolone in a patient sample as homogeneous as possible. In this randomized
double-blind clinical trial, 82 female inpatients with chronic schizophrenia, who
had discontinued their antipsychotic medications for at least one week in case of
any oral antipsychotic medication or a month for any depot antipsychotic
medication, received risperidone plus either pregnenolone (50 mg/day) or placebo
for 8 weeks. Inclusion criteria were acute illness with a baseline Positive and
Negative Syndrome Scale (PANSS) negative subscale score of >=20. Exclusion
criteria were the presence of severe depression or other concomitant psychiatric
disorders. Primary outcome was defined as the difference in the PANSS total score
change from baseline to week 8 in the pregnenolone group compared to the placebo
group. No significant difference was found in the PANSS total score changes
between the two arms (mean difference (CI 95%) = -9.41 (-20.24 to 1.41); p =
0.087). Significant differences were initially found for PANSS negative change
scores (mean difference (CI 95%) = -2.61 (-5.03 to -0.19); p = 0.035) and general
psychopathology change scores (mean difference (CI 95%) = -5.93 (-11.37 to
0.48); p = 0.033). However, these findings did not survive Bonferroni correction
for multiple testing. While this trial may suggest a potential effect of
pregnenolone on schizophrenia symptoms, further studies are warranted.
PMID- 28688339
TI - Brain-derived neurotrophic factor signaling plays a role in resilience to stress
promoted by isoquinoline in defeated mice.
AB - Certain stressful life events have been associated with the onset of depression.
This study aims to investigate if 7-fluoro-1,3-diphenylisoquinoline-1-amine
(FDPI) is effective against social avoidance induced by social defeat stress
model in mice. Furthermore, it was investigated the effects of FDPI in the mouse
prefrontal cortical plasticity-related proteins and some parameters of toxicity.
Adult Swiss mice were subjected to social defeat stress for 10 days. Two
protocols with FDPI were carried out: 1- FDPI (25 mg/kg, intragastric) was
administered to mice 24 h after the last social defeat stress episode; 2- FDPI (1
25 mg/kg, intragastric) was administered to mice once a day for 10 days
concomitant with the social defeat stress. The mice performed social avoidance
and locomotor tests. The prefrontal cortical protein contents of kinase B (Akt),
extracellular signal-regulated kinase (ERK), cAMP-response element binding
protein (CREB), pro-brain-derived neurotrophic factor (proBDNF), p75NTR, neuronal
nuclear protein (NeuN) and nuclear factor-kappaB (NF-kappaB) were determined in
mice. A single administration of FDPI (25 mg/kg) partially protected against
social avoidance induced by stress in mice. Repeated administration of FDPI (25
mg/kg) protected against social avoidance induced by stress in mice. Social
defeat stress decreased the protein contents of p75NTR, NeuN and the pERK/ERK
ratio but increased those of proBDNF and the pCREB/CREB ratio, without changing
that of NF-kappaB. Repeated administration of FDPI modulated signaling pathways
altered by social defeat stress in mice. The present findings demonstrate that
FDPI promoted resilience to stress in mice.
PMID- 28688340
TI - Pesticide tailwater deeply treated by tubular porous electrode reactor (TPER):
Purpose for discharging and cost saving.
AB - Pesticide tailwater often contains residual and toxic contaminants of triazole
fungicides (TFs) due to their poor biodegradability which will do great harm to
local aquatic systems. For this case, a novel electrochemical reactor (TPER)
equipped a tubular porous RuO2-Sb2O5-SnO2 electrode was assembled and then
employed to deeply treat pesticide tailwater. Characterizations of the electrode
studied by SEM, EDS and XRD analysis indicated that it owns a porous structure
and a compact and crack-free surface. Influence of the porous structure on
electrochemical property was examined by cyclic voltammetry and normal pulse
voltammetry. The results indicated that porous structure can not only enlarge
electrochemical active area but also increase mass transfer efficiency by 5.7
fold in flow-through mode compared with batch mode. Furthermore, the optimal
operating conditions of TPER were flow rate of 250 mL min-1 and current density
of 4 mA cm-2. After 1.5 h treatment under these conditions, Tz, TC and PPC were
removed by 98.9%, 99.0% and 98.4% respectively, while 81.9% of COD was also
removed. Additionally, the microbial content was dropped to 0 CFU mL-1 and fecal
coliform was lower than 2 MPN (100 mL)-1. All results demonstrated that the
treated tailwater has met the Class 1 of National Discharge Standard of China.
Especially, operating cost of TPER was only $ 0.33 per ton. The excellent
performance together with the low cost indicated that TPER is a promising option
for depth treatment of industrial tailwater.
PMID- 28688341
TI - International Conference on Heavy Metals in the Environment (ICHMET).
PMID- 28688342
TI - Estrogen-mediated protection of the organotin-degrading strain Metarhizium
robertsii against oxidative stress promoted by monobutyltin.
AB - Dibutyltin (DBT) is a global pollutant characterized by pro-oxidative properties.
The fungal strain Metarhizium robertsii can eliminate high levels of DBT
efficiently. In this study, induction of oxidative stress as well as its
alleviation through the application of natural estrogens during the elimination
of DBT by M. robertsii were evaluated. During the first 24 h of incubation, the
initial concentration of DBT (20 mg l-1) was reduced to 3.1 mg l-1, with
simultaneous formation of a major byproduct - monobutyltin (MBT). In the presence
of estrone (E1) or 17beta-estradiol (E2), the amounts of dibutyltin residues in
the fungal cultures were found to be approximately 2-fold higher compared to
cultures without estrogens, which was associated with the simultaneous
utilization of the compounds by cytochrome P450 enzymes. On the other hand, MBT
levels were approximately 2.5 times lower in the fungal cultures with the
addition of one of the estrogens. MBT (not DBT) promotes the generation of O2-,
H2O2, and NO at levels 65.89 +/- 18.08, 4.04 +/- 3.62, and 27.92 +/- 1.95,
respectively. Superoxide dismutase and catalase activities did not show any
response of the M. robertsii strain against the overproduction of superoxide
anion and hydrogen peroxide. Application of E1 as well as E2 ensured non
enzymatic defense against nitrosative and oxidative stress through scavenging of
nitrogen and oxygen reactive species, and limited their levels from 1.5-fold to
21-fold, depending on the used estrogen.
PMID- 28688343
TI - Evidence for the triadic model of adolescent brain development: Cognitive load
and task-relevance of emotion differentially affect adolescents and adults.
AB - In adults, cognitive control is supported by several brain regions including the
limbic system and the dorsolateral prefrontal cortex (dlPFC) when processing
emotional information. However, in adolescents, some theories hypothesize a
neurobiological imbalance proposing heightened sensitivity to affective material
in the amygdala and striatum within a cognitive control context. Yet, direct
neurobiological evidence is scarce. Twenty-four adolescents (12-16) and 28 adults
(25-35) completed an emotional n-back working memory task in response to happy,
angry, and neutral faces during fMRI. Importantly, participants either paid
attention to the emotion (task-relevant condition) or judged the gender (task
irrelevant condition). Behaviorally, for both groups, when happy faces were task
relevant, performance improved relative to when they were task-irrelevant, while
performance decrements were seen for angry faces. In the dlPFC, angry faces
elicited more activation in adults during low relative to high cognitive load (2
back vs. 0-back). By contrast, happy faces elicited more activation in the
amygdala in adolescents when they were task-relevant. Happy faces also generally
increased nucleus accumbens activity (regardless of relevance) in adolescents
relative to adults. Together, the findings are consistent with neurobiological
models of adolescent brain development and identify neurodevelopmental
differences in cognitive control emotion interactions.
PMID- 28688344
TI - Finding the way forward for forensic science in the US-A commentary on the PCAST
report.
AB - A recent report by the US President's Council of Advisors on Science and
Technology (PCAST), (2016) has made a number of recommendations for the future
development of forensic science. Whereas we all agree that there is much need for
change, we find that the PCAST report recommendations are founded on serious
misunderstandings. We explain the traditional forensic paradigms of match and
identification and the more recent foundation of the logical approach to evidence
evaluation. This forms the groundwork for exposing many sources of confusion in
the PCAST report. We explain how the notion of treating the scientist as a black
box and the assignment of evidential weight through error rates is overly
restrictive and misconceived. Our own view sees inferential logic, the
development of calibrated knowledge and understanding of scientists as the core
of the advance of the profession.
PMID- 28688345
TI - The use of unburned propellant powder for shooting-distance determination. Part
II: Diphenylamine reaction.
AB - Shooting samples were produced on standard textile pats of six different
ammunition types: four ammunitions with exclusively infrared luminescent
propellant powder particles, one containing a mixture of luminescent and non
luminescent particles and one with only non-luminescent particles. Unburned
propellant powder particles in the gunshot residue (GSR) on the textile of each
sample were transferred onto TLC-plates with the aid of an organic solvent. The
patterns of the partially and the all-luminescent propellant powder residue on
the TLC-plates were visualized in the near infrared wavelength range by the aid
of an IR-sensitive camera. The transfer TLC-plates of all six ammunition types
were sprayed with a diphenylamine solution, which reacts with the nitrate groups
of the nitrocellulose and nitroglycerine and produces deep blue dots thereof. A
series of samples with different shooting distances produced with one of the
ammunition types was used for the shooting distance determination study. Transfer
on TLC-plates was performed and pictures of the plates were taken before and
after the chemical reaction. An imaging software was used to measure the density
of the particles on the transfer TLC-plate pictures within a defined area around
the bullet hole. Curves were drawn with the particle density data vs. the
shooting distance. It has been shown, that the transfer of the particles onto a
TLC-plate and the chemical reaction eliminate the limitations of the IR-method
presented in Part I. Therefore, this method allows shooting distance
determination at any textile and for any ammunition type as soon as unburned
propellant powder particles are left on the target tissue.
PMID- 28688346
TI - Improved detection of bovine viral diarrhea virus in bovine lymphoid cell lines
using PrimeFlow RNA assay.
AB - Bovine viral diarrhea virus (BVDV) infections, whether as acute, persistent or
contributing to co-infections, result in significant losses for cattle producers.
Although, BVDV can be identified readily by real-time PCR and ELISA, detection
and quantification of viral infection at the single cell level is extremely
difficult. Detection at the single lymphoid cell level is important due to the
immunomodulation that accompanies BVDV infection. A novel PrimeFlow RNA assay
using in-situ detection of BVDV was evaluated. The model used to develop this
technique included three BL-3 cell lines with different infection statuses, one
not infected with BVDV, one infected with BVDV and one dual infected with BVDV
and bovine leukosis virus. Using RNA probes specific for the BVDV-2a Npro-Erns
coding region, BVDV RNA was detected from both contaminated BL-3 cell lines by
flow cytometry and fluorescent microscopy. This is the first report on in-situ
detection of BVDV at the single-cell level.
PMID- 28688347
TI - Germline polymorphisms on RET proto-oncogene involved in medullary thyroid
carcinoma in a Druze family.
PMID- 28688348
TI - Characterization of iron deficiency symptoms in grapevine (Vitis spp.) leaves by
reflectance spectroscopy.
AB - The work aims at the description of the iron deficiency symptoms in grapevine
leaves by reflectance spectroscopy at the plant and leaf levels. 5 genotypes of
Vitis spp. were selected and grown in hydroponic conditions with and without iron
supply. 450 spectra were collected among basal, young and apical leaves, as well
as veins and interveinal areas. Iron deficiency produced significant and
characteristic modifications in the pigment accumulation, proportion and
distribution in plants. Basal leaves resulted to have higher concentrations of
photosynthetic pigments in stressed plants with respect to the control, probably
due to compensation effects. Iron deficient plants had lower chlorophyll
concentrations in young and apical leaves. In the apical zone, also the relative
composition of pigments appeared to be modified, explaining the reddish-yellowish
apex appearance of iron deficient vines. Finally, the pigment distribution along
the shoot characterized the symptoms, as well as the spectral variations among
veins and interveinal areas. These results could support future applications in
vineyard management (e.g.: symptom identification and detection; precision
fertilization) as well as breeding programs for new rootstock selections (e.g.:
fast screenings of seedlings).
PMID- 28688349
TI - Depressive symptoms and the role of affective temperament in adults with
attention-deficit/hyperactivity disorder (ADHD): A comparison with bipolar
disorder.
AB - OBJECTIVES: To investigate the characteristics of depressive symptoms and the
influence of affective temperament in adults with attention-deficit/hyperactivity
disorder (ADHD), in comparison with bipolar disorder (BD) patients and healthy
controls (HCs). METHOD: Sixty patients with ADHD, 50 patients with BD, and 30 HCs
were assessed with instruments for measuring depressive symptoms (Beck Depression
Inventory-II), and affective temperaments (Temperament Scale of Memphis, Pisa and
San Diego, self-administered version; TEMPS-A). In addition, participants were
evaluated with scales for measuring ADHD symptoms, impulsiveness, anxiety,
executive dysfunction, and quality of life. RESULTS: ADHD patients showed levels
of depressive symptoms similar to BD patients and higher than HCs. Only
neurovegetative symptoms of depression differentiated ADHD and BD groups (BD >
ADHD). Depressive symptoms in ADHD patients correlated positively with core ADHD,
impulsivity, anxiety, and dysexecutive symptoms and negatively with quality of
life. Thirty-eight percent of patients with ADHD scored above the cutoff for at
least one affective temperament. Cyclothymic was the more common affective
temperament (25%). ADHD patients with affective temperamental traits were more
depressed and impulsive than patients without those traits and showed a
symptomatic profile analogous to BD patients. LIMITATIONS: The small size of
resultant samples when ADHD group was stratified by the presence of affective
temperament. In addition, results may not generalize to less severe ADHD patients
from the community. CONCLUSIONS: Concomitant depressive symptoms constitute a
common occurrence in adults with ADHD that carries significant psychopathological
and functional consequences. The concept of affective temperaments may be an
interesting link for explaining depressive symptomatology and emotional
impulsivity in a subgroup of patients with ADHD, beyond the classic idea of
comorbidity.
PMID- 28688350
TI - Changes in the cytokine profile in first-episode, drug-naive patients with
psychosis after short-term antipsychotic treatment.
AB - An increasing body of evidence suggests that antipsychotic medication can cause
immunological changes that could be attributed to the amelioration of psychotic
symptoms or the metabolic side effects of the drugs. So far, the results of the
studies remain controversial. Our aim was to compare the levels of interleukin
(IL) IL-2, IL-6 and transforming growth factor-beta2 (TGF-beta2) in drug-naive,
first-episode patients with psychosis before and after six weeks of antipsychotic
medication. Thirty-nine first-episode patients with psychosis were enrolled in
the study. Serum levels of IL-2, IL-6 and TGF-beta2 were measured by enzyme
linked immunosorbent assay (ELISA) before and six weeks after the initiation of
antipsychotics. In addition, clinical psychopathology was assessed using Positive
and Negative Syndrome Scale (PANSS) before and after treatment. Serum levels of
IL-2 were significantly increased six weeks after the initiation of antipsychotic
treatment (p <0.001) while TGF-beta2 levels were decreased (p <0.001). IL-6
levels were overall increased (p <0.004), but this occurred in a non-linear way.
These findings, although preliminary, provide further evidence that antipsychotic
treatment in patients with psychosis may be correlated with immunological changes
but further research is needed.
PMID- 28688352
TI - Inter-comparison of personal monitors for nanoparticles exposure at workplaces
and in the environment.
AB - Personal monitors based on unipolar diffusion charging (miniDiSC/DiSCmini,
NanoTracer, Partector) can be used to assess the individual exposure to
nanoparticles in different environments. The charge acquired by the aerosol
particles is nearly proportional to the particle diameter and, by coincidence,
also nearly proportional to the alveolar lung-deposited surface area (LDSA), the
metric reported by all three instruments. In addition, the miniDiSC/DiSCmini and
the NanoTracer report particle number concentration and mean particle size. In
view of their use for personal exposure studies, the comparability of these
personal monitors was assessed in two measurement campaigns. Altogether 29
different polydisperse test aerosols were generated during the two campaigns,
covering a large range of particle sizes, morphologies and concentrations. The
data provided by the personal monitors were compared with those obtained from
reference instruments: a scanning mobility particle sizer (SMPS) for LDSA and
mean particle size and a ultrafine particle counter (UCPC) for number
concentration. The results indicated that the LDSA concentrations and the mean
particle sizes provided by all investigated instruments in this study were in the
order of +/-30% of the reference value obtained from the SMPS when the particle
sizes of the test aerosols generated were within 20-400nm and the instruments
were properly calibrated. Particle size, morphology and concentration did not
have a major effect within the aforementioned limits. The comparability of the
number concentrations was found to be slightly worse and in the range of +/-50%
of the reference value obtained from the UCPC. In addition, a minor effect of the
particle morphology on the number concentration measurements was observed. The
presence of particles >400nm can drastically bias the measurement results of all
instruments and all metrics determined.
PMID- 28688353
TI - An in situ method for the high resolution mapping of 137Cs and estimation of
vertical depth penetration in a highly contaminated environment.
AB - The Chernobyl nuclear power plant meltdown has to date been the single largest
release of radioactivity into the environment. As a result, radioactive
contamination that poses a significant threat to human health still persists
across much of Europe with the highest concentrations associated with Belarus,
Ukraine, and western Russia. Of the radionuclides still prevalent with these
territories 137Cs presents one of the most problematic remediation challenges.
Principally, this is due to the localised spatial and vertical heterogeneity of
contamination within the soil (~10's of meters), thus making it difficult to
accurately characterise through conventional measurement techniques such as
static in situ gamma-ray spectrometry or soil cores. Here, a practical solution
has been explored, which utilises a large number of short-count time spectral
measurements made using relatively inexpensive, lightweight, scintillators
(sodium iodide and lanthanum bromide). This approach offers the added advantage
of being able to estimate activity and burial depth of 137Cs contamination in
much higher spatial resolution compared to traditional approaches. During the
course of this work, detectors were calibrated using the Monte Carlo Simulations
and depth distribution was estimated using the peak-to-valley ratio. Activity and
depth estimates were then compared to five reference sites characterised using
soil cores. Estimates were in good agreement with the reference sites,
differences of ~25% and ~50% in total inventory were found for the three higher
and two lower activity sites, respectively. It was concluded that slightly longer
count times would be required for the lower activity (<1MBqm-2) sites. Modelling
and reference site results suggest little advantage would be gained through the
use of the substantially more expensive lanthanum bromide detector over the
sodium iodide detector. Finally, the potential of the approach was demonstrated
by mapping one of the sites and its surrounding area in high spatial resolution.
PMID- 28688351
TI - Correlates of observer-rated active involvement in psychiatric treatment visits.
AB - Among people with serious mental illness, increased patient activation has been
linked to a range of key recovery outcomes. To date, patient activation has been
measured largely through self-report. The present study investigated correlates
of a new tool that assesses active involvement through rating audio-recordings of
treatment visits. The key domains of patient activation assessed in visits
included: patients asking questions, discussing with providers instances of being
active in managing illness outside the session, talking about goals, bringing up
concerns, making evaluative statements about treatment, setting the agenda for
the visit, and making requests about the course of treatment. The new coding
scheme proved to be a feasible and reliable method for identifying multi-faceted
behavioral indicators of patient activation. Contrary to our hypotheses, in a
sample of 166 people diagnosed with severe mental illnesses, self-reported
activation and observer-rated indices of activation were often not correlated or
correlated in unexpected directions with the new behavioral measure of patient
activation. This suggests the nature of patient activation may be complex and
work is needed to understand how observer-rated and self-rated activation may
predict differential recovery outcomes.
PMID- 28688354
TI - Deriving acute and chronic predicted no effect concentrations of pharmaceuticals
and personal care products based on species sensitivity distributions.
AB - Pharmaceuticals and personal care products (PPCPs), as emerging contaminants,
have been detected in various environmental matrices and caused adverse effects
on human health and the ecosystem. But water quality criterias (WQCs) of PPCPs
for protecting aquatic environment are lacking, which hinders the environmental
management of these emerging contaminants. In the present study, in order to
support their WQC derivation, acute and chronic hazardous concentrations for 5%
of species (HC5s) of some frequently detected PPCPs in China were calculated
based on acute and chronic species sensitivity distributions (SSDs),
respectively, using both parametric (log-normal and log-logistic) and
nonparametric bootstrap approaches. The groups of aquatic species used in SSDs
included planktons, zooplanktons, invertebrates and vertebrates. Acute and
chronic predicted no effect concentrations (PNECs) were derived from the HC5s.
The acute PNECs of the selected PPCPs were in a range from 1.1 to 4993MUg/L.
While the chronic PNECs were one or two orders of magnitude lower than the acute
PNECs, with a range from 0.02 to 298MUg/L. Among these PPCPs, the compound with
the highest acute effect on the aquatic environment was clarithromycin while
erythromycin was the one with the highest chronic toxicity effect. Among the
studied PPCPs, erythromycin caused a relatively higher aquatic ecological risk in
China. This study helps derive WQCs of PPCPs in the aquatic environment, which is
essential for environmental managment of these emerging contaminants.
PMID- 28688355
TI - Bioavailability of coated and uncoated ZnO nanoparticles to cucumber in soil with
or without organic matter.
AB - There is a gap of knowledge for the fate, effects and bioavailability of coated
and uncoated ZnO nanoparticles (NPs) in soil. Moreover, little is known about the
effects of soil properties on effects of NPs on plants. In this study, the
availability ZnO NPs in two soils with different organic matter content (one
treated with cow manure (CM) and the other as untreated) was compared with their
bulk particles. Results showed that coated and uncoated ZnO NPs can be more
bioaccessible than their bulk counterpart and despite their more positive effects
at low concentration (< 100mgkg-1), they were more phytotoxic for plants compared
to the bulk ZnO particles at high concentration (1000mgkg-1) in the soil
untreated with CM. The concentration of 1000mgkg-1 of ZnO NPs, decreased shoot
dry biomass (52%) in the soil untreated with CM but increased shoot dry biomass
(35%) in CM-treated soil compared to their bulk counterpart. In general, plants
in the CM-treated soil showed higher Zn concentration in their tissues compared
with those in untreated soil. The difference in shoot Zn concentration between CM
treated and untreated soil for NPs treatments was more than bulk particles
treatment. This different percentage at 100mgkg-1 of bulk particles was 20.6% and
for coated and uncoated NPs were 37% and 32%, respectively. Generally, the
distribution of ZnO among Zn fractions in soil (exchangeable, the metal bound to
carbonates, Fe-Mn oxides, organic matter and silicate minerals and the residual
fraction) changed based on applied Zn concentration, Zn source and soil organic
matter content. The root tip deformation under high concentration of NPs
(1000mgkg-1 treatment) was observed by light microscopy in plants at the soil
untreated with CM. It seems that root tip deformation is one of the specific
effects of NPs which in turn inhibits plant growth and nutrients uptake by root.
The transmission electron microcopy image showed the aggregation of NPs inside
the plant cytoplasm and their accumulation adjacent to the cell membrane.
PMID- 28688356
TI - Evaluation of biomarkers for ecotoxicity assessment by dose-response dynamic
models: Effects of nitrofurazone on antioxidant enzymes in the model ciliated
protozoan Euplotes vannus.
AB - Understanding dose-responses is crucial for determining the utility of biomarkers
in ecotoxicity assessment. Nitrofurazone is a broad-spectrum antibiotic that is
widely used in the aquaculture industry in China despite its detrimental effects
on ecosystems. Potential dose-response models were examined for the effect of
nitrofurazone on two antioxidant enzymes, superoxide dismutase (SOD) and
glutathione peroxidase (GPx), in the ciliated protozoan Euplotes vannus. This was
achieved by measuring enzyme activity and gene expression profiling of SOD and
GPx in ciliate cells exposed to nitrofurazone at doses ranging from 0 to 180mgl-1
for 6h, 12h, 18h and 24h. Dose-response dynamics were characterized by
mathematical models. Results showed that: 1) dose-response patterns differed
significantly among the tested endpoints, nitrofurazone concentrations and
durations of exposure; 2) GPx activity was the best candidate biomarker because
of its linear dose-response relationship; 3) SOD activity and mRNA relative
expression levels of GPx and SOD are also candidate biomarkers but their dose
responses were non-linear and therefore more difficult to interpret; 4)
partitioning the dose-response dynamic model by piecewise function can help to
clarify the relationships between biological endpoints. This study demonstrates
the utility of dynamic model analysis and the potential of antioxidant enzymes,
in particular GPx activity, as a candidate biomarkers for environmental
monitoring and risk assessment of nitrofurazone in the aquaculture industry.
PMID- 28688357
TI - Revealing chemophoric sites in organophosphorus insecticides through the MIA-QSPR
modeling of soil sorption data.
AB - Soil sorption of insecticides employed in agriculture is an important parameter
to probe the environmental fate of organic chemicals. Therefore, methods for the
prediction of soil sorption of new agrochemical candidates, as well as for the
rationalization of the molecular characteristics responsible for a given sorption
profile, are extremely beneficial for the environment. A quantitative structure
property relationship method based on chemical structure images as molecular
descriptors provided a reliable model for the soil sorption prediction of 24
widely used organophosphorus insecticides. By means of contour maps obtained from
the partial least squares regression coefficients and the variable importance in
projection scores, key molecular moieties were targeted for possible structural
modification, in order to obtain novel and more environmentally friendly
insecticide candidates. The image-based descriptors applied encode molecular
arrangement, atoms connectivity, groups size, and polarity; consequently, the
findings in this work cannot be achieved by a simple relationship with
hydrophobicity, usually described by the octanol-water partition coefficient.
PMID- 28688358
TI - Trace element concentrations in feathers and blood of Northern goshawk (Accipiter
gentilis) nestlings from Norway and Spain.
AB - Information on trace element pollution in the terrestrial environment and its
biota is limited compared to the marine environment. In the present study, we
collected body feathers and blood of 37 Northern goshawk (Accipiter gentilis)
nestlings from Tromso (northern Norway), Trondheim (central Norway), and Murcia
(southeastern Spain) to study regional exposure, hypothesizing the potential
health risks of metals and other trace elements. Blood and body feathers were
analyzed by a high resolution inductively coupled plasma mass spectrometer (HR
ICP-MS) for aluminum (Al), nickel (Ni), copper (Cu), zinc (Zn), arsenic (As),
selenium (Se), cadmium (Cd), mercury (Hg) and lead (Pb). The influence of
regional differences, urbanization and agricultural land usage in proximity to
the nesting Northern goshawks was investigated using particular spatial analysis
techniques. Most trace elements were detected below literature blood toxicity
thresholds, except for elevated concentrations (mean +/- SD ugml-1 ww) found for
Zn (5.4 +/- 1.5), Cd (0.00023 +/- 0.0002), and Hg (0.021 +/- 0.01). Corresponding
mean concentrations in feathers (mean +/- SD ugg-1 dw) were 82.0 +/- 12.4, 0.0018
+/- 0.002, and 0.26 +/- 0.2 for Zn, Cd and Hg respectively. Multiple linear
regressions indicated region was a significant factor influencing Al, Zn, Se and
Hg feather concentrations. Blood Cd and Hg concentrations were significantly
influenced by agricultural land cover. Urbanization did not have a significant
impact on trace element concentrations in either blood or feathers. Overall metal
and trace element levels do not indicate a high risk for toxic effects in the
nestlings. Levels of Cd in Tromso and Hg in Trondheim were however above sub
lethal toxic threshold levels. For holistic risk assessment purposes it is
important that the concentrations found in the nestlings of this study indicate
that terrestrial raptors are exposed to various trace elements.
PMID- 28688359
TI - Influence of silicon treatment on antimony uptake and translocation in rice
genotypes with different radial oxygen loss.
AB - Antimony (Sb) pollution in soil may have a negative impact on the health of
people consuming rice. This study investigated the effect of silicon (Si)
application on rice biomass, iron plaque formation, and Sb uptake and speciation
in rice plants with different radial oxygen loss (ROL) using pot experiments. The
results demonstrated that Si addition increased the biomass of straw and grain,
but had no obvious impact on the root biomass. Indica genotypes with higher ROL
underwent greater iron plaque formation and exhibited more Sb sequestration in
iron plaque. Silicon treatments increased iron levels in iron plaque from the
different genotypes but decreased the total Sb concentration in root, straw,
husk, and grain. In addition, Si treatment reduced the inorganic Sb
concentrations but slightly increased the trimethylantimony (TMSb) concentrations
in rice straw. Moreover, rice straw from hybrid genotypes accumulated higher
concentrations of TMSb and inorganic Sb than that from indica genotypes. The
conclusions from this study indicate that Sb contamination in rice can be
efficiently reduced by applying Si treatment and selecting genotypes with high
ROL.
PMID- 28688360
TI - Microbial functional diversity responses to 2 years since biochar application in
silt-loam soils on the Loess Plateau.
AB - The structure and function of soil microbial communities have been widely used as
indicators of soil quality and fertility. The effect of biochar application on
carbon sequestration has been studied, but the effect on soil microbial
functional diversity has received little attention. We evaluated effects of
biochar application on the functional diversities of microbes in a loam soil. The
effects of biochar on microbial activities and related processes in the 0-10 and
10-20cm soil layers were determined in a two-year experiment in maize field on
the Loess Plateau in China. Low-pyrolysis biochar produced from maize straw was
applied into soils at rates of 0 (BC0), 10 (BC10) and 30 (BC30)tha-1. Chemical
analysis indicated that the biochar did not change the pH, significantly
increased the amounts of organic carbon and nitrogen, and decreased the amount of
mineral nitrogen and the microbial quotient. The biochar significantly decreased
average well colour development (AWCD) values in Biolog EcoPlatesTM for both
layers, particularly for the rate of 10tha-1. Biochar addition significantly
decreased substrate richness (S) except for BC30 in the 0-10cm layer. Effects of
biochar on the Shannon-Wiener index (H) and Simpson's dominance (D) were not
significant, except for a significant increase in evenness index (E) in BC10 in
the 10-20cm layer. A principal component analysis clearly differentiated the
treatments, and microbial use of six categories of substrates significantly
decreased in both layers after biochar addition, although the use of amines and
amides did not differ amongst the three treatments in the deeper layer. Maize
above ground dry biomass and height did not differ significantly amongst the
treatments, and biochar had no significant effect on nitrogen uptake by maize
seedlings. H was positively correlated with AWCD, and negatively with pH. AWCD
was positively correlated with mineral N and negatively with pH. Our results
indicated that shifts in soil microbial functional diversity affected by biochar
were not effective indicators of soil quality in earlier maize growth periods in
this region.
PMID- 28688362
TI - pH dependent silver nanoparticles releasing titanium implant: A novel therapeutic
approach to control peri-implant infection.
AB - Peri-implant infection control is crucial for implant fixation and durability.
Antimicrobial administration approaches to control peri-implant infection are far
from satisfactory. During bacterial infection, pH level around the peri-implant
surface decreases as low as pH 5.5. This change of pH can be used as a switch to
control antimicrobial drug release from the implant surface. Silver nanoparticles
(AgNPs) have broad-spectrum antimicrobial properties. In this study, we aimed to
design a pH-dependent AgNPs releasing titania nanotube arrays (TNT) implant for
peri-implant infection control. The nanotube arrays were fabricated on the
surface of titanium implant as containers; AgNPs were grafted on TNT implant
surface via a low pH-sensitive acetal linker (TNT-AL-AgNPs). SEM, TEM, AFM, FTIR
as well as XPS data showed that AgNPs have been successfully linked to TNT via
acetal linker without affecting the physicochemical characteristics of TNT. The
pH 5.5 enhanced AgNPs release from TNT-AL-AgNPs implant compared with pH 7.4.
AgNPs released at pH 5.5 robustly increased antimicrobial activities against gram
positive and gram-negative bacteria compared with AgNPs released at pH 7.4. TNT
AL-AgNPs implant enhanced osteoblast proliferation, differentiation, and did not
affect osteoblast morphology in vitro. In conclusion, incorporation of AgNPs in
TNT via acetal linker maintained the surface characteristics of TNT. TNT-AL-AgNPs
implant was biocompatible to osteoblasts and showed osteoinductive properties.
AgNPs were released from TNT-AL-AgNPs implant in high dose at pH 5.5, and this
release showed strong antimicrobial properties in vitro. Therefore, this novel
design of low pH-triggered AgNPs releasing TNT-AL-AgNPs could be an infection
triggered antimicrobial releasing implant model to control peri-implant
infection.
PMID- 28688361
TI - A survey of 17alpha-ethinylestradiol and mestranol residues in Hawkesbury River,
Australia, using a highly specific enzyme-linked immunosorbent assay (ELISA)
demonstrates the levels of potential biological significance.
AB - This study reports on the potential status of 17alpha-ethinylestradiol (EE2) and
mestranol (MeEE2) residues in aquatic environments in New South Wales (NSW),
Australia, based on the analysis by a specific ELISA we developed. Polyclonal
antibodies were raised against the EE2 hapten with a linker attached at the C3
position to direct the antibody binding towards the ring D of EE2/MeEE2. Using
this approach, an ELISA highly specific to EE2 and MeEE2 was successfully
developed, showing less than 3.1% cross-reactivity (% CR) with other major
steroidal sex hormones and their derivatives. The assay performed with the limit
of detection (LOD) of 0.04 +/- 0.01ug/L for both EE2 and MeEE2, and the limit of
quantitation (LOQ) of 0.05 +/- 0.01ng/L when it was coupled with the SM2-Biobeads
solid phase extraction. Prior to conducting the survey study, it was validated
against the gas chromatography-mass spectrophotometry (GC-MS) method, which
showed high correlation with R2 of 0.934. Fresh surface water samples collected
at different sites along Hawkesbury River in New South Wales (NSW) were analyzed
for the EE2/ MeEE2 residues using the developed ELISA. The EE2/MeEE2 levels were
found to range between 4.1 and 8.3ng/L in Emigrant Creek, NSW, where the primary
activity was macadamia plantation, and higher levels between 15 and 29ng/L in
South Creek, NSW, Greater Western Sydney at sites upstream and downstream of the
municipal sewage treatment plants.
PMID- 28688363
TI - Modulating in vitro gastric digestion of emulsions using composite whey protein
cellulose nanocrystal interfaces.
AB - In this study, we designed emulsions with an oil-water interface consisting of a
composite layer of whey protein isolate (WPI, 1wt%) and cellulose nanocrystals
(CNCs) (1-3wt%). The hypothesis was that a secondary layer of CNCs at the WPI
stabilized oil-water interface could protect the interfacial protein layer
against in vitro gastric digestion by pepsin at 37 degrees C. A combination of
transmission electron microscopy, zeta-potential measurements, interfacial shear
viscosity measurements and theoretical surface coverage considerations suggested
the presence of CNCs and WPI together at the O/W interface, owing to the
electrostatic attraction between complementarily charged WPI and CNCs at pH 3.
Microstructural analysis and droplet sizing revealed that the presence of CNCs
increased the resistance of the interfacial protein film to rupture by pepsin,
thus inhibiting droplet coalescence in the gastric phase, which occurs rapidly in
an emulsion stabilized by WPI alone. It appeared that there was an optimum
concentration of CNCs at the interface for such barrier effects. Sodium dodecyl
sulphate polyacrylamide gel electrophoresis (SDS-PAGE) results further confirmed
that the presence of 3wt% of CNCs reduced the rate and extent of proteolysis of
protein at the interface. Besides, evidence of adsorption of CNCs to the protein
coated droplets to form more rigid layers, there is also the possibility that
network formation by the CNCs in the bulk (continuous) phase reduced the kinetics
of proteolysis. Nevertheless, structuring emulsions with mixed protein-particle
layers could be an effective strategy to tune and control interfacial barrier
properties during gastric passage of emulsions.
PMID- 28688364
TI - In vivo study of microarc oxidation coated biodegradable magnesium plate to heal
bone fracture defect of 3mm width.
AB - Microarc oxidation (MAO) coated magnesium (Mg) with improved corrosion resistance
appeal increasing interests as a revolutionary biodegradable metal for fractured
bone fixing implants application. However, the in vivo corrosion degradation of
the implants and bone healing response are not well understood, which is highly
required in clinic. In the present work, 10MUm and 20MUm thick biocompatible MAO
coatings mainly composed of MgO, Mg2SiO4, CaSiO3 and Mg3(PO4)2 phases were
fabricated on AZ31 magnesium alloy. The electrochemical tests indicated an
improved corrosion resistance of magnesium by the MAO coatings. The 10MUm and
20MUm coated and uncoated magnesium plates were separately implanted into the
radius bone fracture site of adult New Zealand white rabbits using a 3mm width
bone fracture defect model to investigate the magnesium implants degradation and
uninhibited bone healing. Taking advantage of the good biocompatibility of the
MAO coatings, no adverse effects were detected through the blood test and
histological examination. The implantation groups of coated and uncoated
magnesium plates were both observed the promoting effect of bone fracture healing
compared with the simple fracture group without implant. The releasing Mg2+ by
the degradation of implants into the fracture site improved the bone fracture
healing, which is attributed to the magnesium promoting CGRP-mediated osteogenic
differentiation. Mg degradation and bone fracture healing promoting must be
tailored by microarc oxidation coating with different thickness for potential
clinic application.
PMID- 28688365
TI - Albumin nanoparticles with synergistic antitumor efficacy against metastatic lung
cancers.
AB - Albumin nanoparticles are well-known as effective drug carriers used to deliver
hydrophobic chemotherapeutic agents. Albumin nanoparticles encapsulating curcumin
and doxorubicin were fabricated using slightly modified nanoparticle albumin
bound (nabTM) technology, and the synergistic effects of these two drugs were
examined. Albumin nanoparticles encapsulating curcumin, doxorubicin, and both
curcumin and doxorubicin were prepared using a high pressure homogenizer. The
sizes of albumin nanoparticles were ~130nm, which was considered to be suitable
for the EPR (enhanced permeability and retention) effect. Albumin nanoparticles
gradually released drugs over a period of 24h without burst effect. To confirm
the synergistic effect of two drugs, in vitro cytotoxicity assay was performed
using B16F10 melanoma cells. The cytotoxic effect on B16F10 melanoma cells was
highest when co-treated with both curcumin and doxorubicin compared to single
treatment of either curcumin and doxorubicin. The combined index calculated by
medium-effect equation was 0.6069, indicating a synergistic effect. Results of
confocal laser scanning microscopy and fluorescence-activated cell sorting
corresponded to results from an in vitro cytotoxicity assay, indicating
synergistic cytotoxicity induced by both drugs. A C57BL/6 mouse model induced by
B16F10 lung metastasis was used to study in vivo therapeutic effects. When
curcumin and doxorubicin were simultaneously treated, the metastatic melanoma
mass in the lungs macroscopically decreased compared to curcumin or doxorubicin
alone. Albumin nanoparticles encapsulating two anticancer drugs were shown to
have an effective therapeutic result and would be an excellent way to treat
resistant lung cancers.
PMID- 28688366
TI - Differentiation of Flavobacterium psychrophilum from Flavobacterium psychrophilum
like species by MALDI-TOF mass spectrometry.
AB - Rainbow trout fry syndrome (RTFS) is an important infectious disease caused by
Flavobacterium psychrophilum affecting farmed salmonids worldwide. Other
Flavobacterium psychrophilum-like species (F. plurextorum, F. oncorhynchi, F.
tructae, F. collinsii and F. piscis) have been isolated from diseased rainbow
trout fry suspected of RTFS although the epidemiological and clinical relevance
of these pathogens are unknown. The objective of this study was to evaluate the
potential use of MALDI-TOF (Matrix-Assisted Laser Desorption/Ionization-Time of
Flight) Mass Spectrometry as method for specific identification of F.
psychrophilum and its differentiation from other F. psychrophilum-like species
isolated from diseased fish. Fifty-three isolates were analyzed after the
creation of the Main Spectrum Profile (MSP) of reference strains of each of
abovementioned species. F. psychrophilum exhibited a mass spectra very different
from those of F. psychrophilum-like species, with five peaks (m/z 3654, 4585,
5388, 6730 and 7310) present only in F. psychrophilum isolates, and three peaks
(m/z 6170, 7098 and 9241) absent in F. psychrophilum but present in all F.
psychrophilum-like species. All F. psychrophilum isolates were correctly
identified and differentiated from the F. psychrophilum-like species by MALDI
TOF. Although this approach showed a limited ability to differentiate among F.
psychrophilum-like species, its complementation with a few simple biochemical
tests may represent an alternative approach for the routine identification of the
Flavobacterium psychrophilum-like species.
PMID- 28688368
TI - "Hydrous 18F-fluoroethylation" - Leaving off the azeotropic drying.
AB - The study describes the development of a simple and effective method for 18F
fluoroethylation -omitting the azeotropic drying step- by elution of a
[18F]fluoride loaded QMA column with a K2CO3/K222/acetonitrile solution
containing 2-3% (v/v) water directly to the 1,2-ethylene glycol-bis-tosylate
precursor. In acetonitrile containing 2-3% (v/v) water the labeling agent 2
[18F]fluoroethyl tosylate ([18F]FETs) was formed in 76-96% non-isolated
radiochemical yield. The method was exemplified on the 18F-fluoroethylation of
three COX-2 inhibitors with different core structures. The superiority of the so
called "hydrous 18F-fluoroethylation" is characterized by a minimum loss of
[18F]fluoride, by fivefold increased radiochemical yield of isolated final
radiotracers and by shortened overall reaction time, in comparison to
conventional approach.
PMID- 28688367
TI - Postural motor learning in Parkinson's disease: The effect of practice on
continuous compensatory postural regulation.
AB - INTRODUCTION: Although balance training is considered the most effective
treatment for balance impairments in Parkinson's disease (PD), few studies have
examined if learning for balance control remains intact with PD. This study aimed
to determine if learning for automatic postural responses is preserved in people
with PD. METHODS: Eleven participants with moderate PD (68+/-6.4years; H&Y: 2-3)
on their usual medication maintained balance on a platform that oscillated
forward and backward with variable amplitude and constant frequency. Participants
completed 42 trials during one training session, and retention and transfer tests
following a 24-h delay. Performance was measured by comparing spatial and
temporal measures of whole-body centre of mass (COM) with platform displacements.
Learning was compared between participants with PD and previously reported, age
matched older adults (Van Ooteghem et al., 2010). RESULTS: Although postural
responses in participants with PD were impaired compared to control participants,
a majority of PD participants improved their postural responses with practice as
revealed by reduced COM displacements and improved phase relationships between
COM and platform motion. Rates of improvement were comparable between groups
demonstrating preserved adaptive capacity for participants with PD. Similar to
control participants, the PD group moved toward anticipatory COM control as a
strategy for improving stability, exhibited short-term retention of performance
improvements, and demonstrated generalizability of the learned responses. Rate of
improvement with practice, but not retention, was related to severity of motor
impairments. CONCLUSIONS: Patients with moderate PD on medication demonstrate
retention of improvements in automatic postural responses with practice
suggesting that intrinsic postural motor learning is preserved in this group.
PMID- 28688369
TI - Evaluation of diet quality of the elderly and associated factors.
AB - BACKGROUND: Observational studies suggest healthy dietary patterns are associated
with risk reduction and better control of various chronic diseases. However, few
Brazilian studies have focused on evaluating the quality of the elderly diet and
its relationship with diseases. This study aimed to estimate the association
between diet quality and socioeconomic factors, health and nutrition of the
elderly. METHODS: This is a cross-sectional population-based study whose target
population were non-institutionalized elderly residents in the city of Vicosa,
Brazil. Anthropometric, socioeconomic, health conditions, lifestyle and food
consumption variables were obtained from a semi-structured questionnaire. The
quality of the diet was assessed by the revised Healthy Eating Index classified
into tertiles, considering the first tertile as "Poor diet quality," the second
as 'Intermediate diet quality' and the third as "Better diet quality." To
identify factors independently associated with diet quality model, the works used
multinomial logistic regression. RESULTS: In the results of the multivariate
analysis, the factors independently associated with "better diet quality"
included female gender, higher education, history of one to five medical visits
in the past year, history of diabetes mellitus, dyslipidemia and the use of
polypharmacy. DISCUSSION: Our results show that most seniors need to improve the
quality of their diet and those of male gender with no or little education, and
those who do not seek medical services constitute the group that needs attention
concerning the measures to improve the quality of their diet.
PMID- 28688370
TI - Whole transcriptome RNAseq analysis of Oenococcus oeni reveals distinct intra
specific expression patterns during malolactic fermentation, including genes
involved in diacetyl metabolism.
AB - We report the first whole transcriptome RNAseq analysis of the wine-associated
lactic acid bacterium Oenococcus oeni using a combination of reference-based
mapping and de novo transcript assembly in three distinct strains during
malolactic fermentation in Cabernet Sauvignon wine. Two of the strains (AWRIB551
and AWRIB552) exhibited similar transcriptomes relative to the third strain
(AWRIB419) which was dissimilar by comparison. Significant intra-specific
variation for genes related to glycolysis/gluconeogenesis, purine metabolism,
aminoacyl-tRNA biosynthesis, ABC transporters and phosphotransferase systems was
observed. Importantly, thirteen genes associated with the production of diacetyl,
a commercially valuable aroma and flavour compound, were also found to be
differentially expressed between the strains in a manner that correlated
positively with total diacetyl production. This included a key strain-specific
gene that is predicted to encode a l-lactate dehydrogenase that may enable l
lactic acid to be utilised as a precursor for the production of diacetyl. In
conjunction with previous comparative genomic studies of O. oeni, this study
progresses the understanding of genetic variations which contribute to the
phenotypes of this industrially-important bacterium.
PMID- 28688371
TI - 6:2 fluorotelomer carboxylic acid (6:2 FTCA) exposure induces developmental
toxicity and inhibits the formation of erythrocytes during zebrafish
embryogenesis.
AB - Saturated fluorotelomer carboxylic acids (FTCAs) are intermediates in the
degradation of fluorotelomer alcohols (FTOHs) to perfluorinated carboxylic acids
(PFCAs). Recent studies have detected FTCAs in precipitation, surface waters, and
wildlife, but few studies have focused on their toxicity. In this study,
zebrafish embryos were exposed to different concentrations of 6:2 FTCA (0, 4, 8,
and 12mg/L) from 6 to 120h post-fertilization (hpf) to investigate its
developmental toxicity. Results showed that 6:2 FTCA exposure decreased the
hatching and survival percentages, reduced the heart rate, and increased the
malformation of zebrafish embryos. The median lethal concentration of 6:2 FTCA
was 7.33mg/L at 120 hpf, which was lower than that of perfluorooctanoic acid
(PFOA), thus indicating higher toxicity for zebrafish. The most common
developmental malformation was pericardial edema, which appeared in the 8 and
12mg/L 6:2 FTCA-exposed embryos from 60 hpf. Using o-dianisidine staining, we
found that the hemoglobin content in embryos was reduced in a concentration
dependent manner after 6:2 FTCA exposure at 72 hpf. Based on quantitative real
time polymerase chain reaction (q-RT-PCR) and whole-mount in situ hybridization,
the transcriptional levels of hemoglobin markers (hbae1, hbbe1, and hbae3) were
down-regulated at 48 and 72 hpf, even though no observed malformation appeared in
zebrafish at 48 hpf. Moreover, 6:2 FTCA exposure decreased the protein level of
gata1, a principal early erythrocytic marker, in Tg (gata1:DsRed) transgenic
zebrafish at 72 hpf. We analyzed the transcriptional level of other erythrocyte
related genes using q-RT-PCR assay. For heme formation, the transcription of
alas2, which encodes the key enzyme for heme biosynthesis, was down-regulated
after 6:2 FTCA exposure, whereas the transcription of ho-1, which is related to
heme degradation, was up-regulated at 48 and 72 hpf. The transcriptional patterns
of gata1 and gata2, which are related to erythroid differentiation, differed. At
48 hpf, the mRNA level of gata2 was significantly increased, whereas that of
gata1 exhibited no significant changes in any treatment group. At 72 hpf, the
expressions of both were down-regulated in a concentration-dependent manner.
Taken together, 6:2 FTCA exposure decreased the erythrocyte number and disrupted
erythroid differentiation during zebrafish embryonic development. Our results
suggest that 6:2 FTCA can cause developmental toxicity in zebrafish embryos, and
that FTCAs exhibit greater toxicity than that of PFCAs.
PMID- 28688372
TI - Re-assessing the vertical distribution of testate amoeba communities in surface
peats: Implications for palaeohydrological studies.
AB - Testate amoeba-derived transfer functions are frequently used in peatland
palaeohydrological studies and involve the development of training sets from
surficial peats. However, within acrotelmic peats, considerable vertical
variation in assemblage composition can occur, particularly along Sphagnum stems,
which may limit the representation of the associated 'contemporary' testate
amoeba samples as analogues for the peatland surface. This paper presents
contiguous testate amoeba assemblage data from nine monoliths collected from
different peatland microforms (hummock, hollow, lawn) in three Sphagnum dominated
ombrotrophic peatlands in Ontario and Quebec, eastern Canada. The aim is to: (i)
gain a greater understanding of the vertical distribution of
xerophilous/hygrophilous taxa along Sphagnum stems; (ii) determine the vertical
extent of live/encysted taxa along this gradient; and (iii) assess the
significance of this distribution on surface sampling protocols. The results show
that testate amoeba communities in the uppermost acrotelmic peat layers display
considerable variability. This may reflect a complex interplay of abiotic and
biotic controls, including moisture, temperature, light and other
characteristics, food availability, and mineral particle availability for test
construction. These findings underline the complexity of testate amoeba community
structure and highlight the importance of analysing both living and dead Sphagnum
stem sections when developing calibration sets.
PMID- 28688373
TI - Deletion of RDINK4/ARF enhancer: A novel mutation to "inactivate" the INK4-ARF
locus.
AB - The presence of an enhancer element, RDINK4/ARF (RD), in the prominent INK4-ARF
locus provides a novel en bloc mechanism to simultaneously regulate the
transcription of the p15INK4B (p15), p16INK4A (p16), and p14ARF tumor suppressor
genes. While genetic inactivation of p15, p16, and p14ARF in human cancers has
been extensively studied, little is known about RD alteration and its potential
contributions to cancer progression. In this review, we discuss recent
developments in RD alteration and its association with p15, p16, and p14ARF
alterations in human cancers, and demonstrate that RD deletion may represent a
novel mechanism to simultaneously down-regulate p15, p16, and p14ARF, thus
promoting carcinogenesis.
PMID- 28688374
TI - Luminescence and energy transfer of Tb3+-doped BaO-Gd2O3-Al2O3-B2O3-SiO2 glasses.
AB - Transparent Tb3+-doped BaO-Gd2O3-Al2O3-B2O3-SiO2 glasses with the greater than
4g/cm3 were prepared by high temperature melting method and its luminescent
properties have been investigated by measured UV-vis transmission, excitation,
emission and luminescence decay spectra. The transmission spectrum shows there
are three weak absorption bands locate at about 312, 378 and 484nm in the glasses
and it has good transmittance in the visible spectrum region. Intense green
emission can be observed under UV excitation. The effective energy transfer from
Gd3+ ion to Tb3+ ion could occur and sensitize the luminescence of Tb3+ ion. The
green emission intensity of Tb3+ ion could change with the increasing SiO2/B2O3
ratio in the borosilicate glass matrix. With the increasing concentration of Tb3+
ion, 5D4->7FJ transitions could be enhanced through the cross relaxation between
the two nearby Tb3+ ions. Luminescence decay time of 2.12ms from 546nm emission
is obtained. The results indicate that Tb3+-doped BaO-Gd2O3-Al2O3-B2O3-SiO2
glasses would be potential scintillating material for applications in X-ray
imaging.
PMID- 28688375
TI - DFT and TD-DFT study of isomeric 5-(pyridyl)-1,3,4-oxadiazol-2-thiones and 2
methylthio-5-(pyridyl)-1,3,4-oxadiazoles.
AB - Internal rotations of pyridine fragment around single bond of isomeric 5-(2', 3'
and 4'-pyridyl)-1,3,4-oxadiazol-2-thiones and 2-methylthio-5-(2', 3' and 4'
pyridyl)-1,3,4-oxadiazoles have been performed by DFT (B3LYP) and MP2 methods
with RHF/6-31G(d,p) basis set. It was found that the MP2 barrier height lies a
few below than DFT barrier heights for all studied compounds. In the molecule of
2-methylthio-5-(2'-pyridyl)-1,3,4-oxadiazole an anomeric effect detected due to a
lone pair-lone pair interaction of pyridine and N4 oxadiazole nitrogen atoms. But
it not found in the molecule of 5-(2'-pyridyl)-1,3,4-oxadiazol-2-thione.
Furthermore, theoretical UV spectra of the compounds were studied using TD-DFT/6
31G(d,p) method. Theoretical transitions located about 10nm in the long
wavelength region relatively to the experimental bands field. Whereas, the
theoretical transitions of 2-methylthio-5-(2', 3' and 4'-pyridyl)-1,3,4
oxadiazoles have very good agreement with the position of experimental bands. The
longest wavelength band in both of experimental and theoretical spectra of the
investigated compounds have been observed for 5-(4'-pyridyl)-1,3,4-oxadiazole-2
thione and 2-methylthio-5-(2'-pyridyl)-1,3,4-oxadiazole. Furthermore, the longest
wavelength experimental band's position are in good agreement with (r2=0.95) the
HOMO-LUMO energetic gaps of studied compounds.
PMID- 28688376
TI - Molecular Identification and Antifungal Susceptibility Pattern of Non-albicans
Candida Species Isolated from Vulvovaginal Candidiasis
AB - Background: Vulvovaginal candidiasis (VVC) is an important health problem caused
by Candida spp. The aim of this study was molecular identification, phylogenetic
analysis, and evaluation of antifungal susceptibility of non-albicans Candida
isolates from VVC. Methods: Vaginal secretion samples were collected from 550
vaginitis patients at Sayyad Shirazi Medical and Educational Center of Gorgan
(Golestan Province, Iran) from May to October 2015. Samples were analyzed using
conventional mycological and molecular approaches. Clinical isolates were
analyzed with specific PCR using CGL primers, and the internal transcribed spacer
region and the D1-D2 domain of the large-subunit rRNA gene were amplified and
sequenced. Susceptibility to amphotericin B, fluconazole, itraconazole, and
clotrimazole was determined by the guidelines of the Clinical and Laboratory
Standard Institute. Results: In total, 35 non-albicans Candida isolates were
identified from VVC patients. The isolates included 27 strains of Candida
glabrata (77.1%), 5 Candida krusei (Pichia kudriavzevii; 14.3%), 2 Candida kefyr
(Kluyveromyces marxianus; 5.7%), and 1 Candida lusitaniae (Clavispora lusitaniae;
2.9%). The fungicides itraconazole and amphotericin B were effective against all
species. One isolate of C. glabrata showed resistance to fluconazole and
clotrimazole, and 26 isolates of C. glabrata indicated dose-dependent
susceptibility to fluconazole. C. lusitaniae was susceptible in a dose-dependent
manner to fluconazole and resistant to clotrimazole. Conclusion: Non-albicans
Candida spp. are common agents of vulvovaginitis, and C. glabrata is the most
common species in the tested patients.
PMID- 28688378
TI - Self-assembly of Janus disks induced by small molecules in two-dimensional
systems.
AB - We study the co-assembly of amphiphilic Janus disks and isotropic molecules by
Monte Carlo simulations. A Janus particle is composed of two parts, one being
attractive, A, and the other one being repulsive, R. Fluid molecules are strongly
attracted by the R-sides and repelled by the A-sides. As the fluid density
increases, the structure of the system changes from chaotically distributed Janus
particles, through lamellar-like and gel-like structures, to the phase containing
finite aggregates of Janus particles dispersed in the fluid. We show that
"adsorption" of fluid molecules on the R-parts of Janus particles plays a key
role in the co-assembly. The bond-switching between Janus particles is observed
as the fluid density varies.
PMID- 28688377
TI - No Role of Herpes Simplex Virus Type 2 (HSV-2) Infection on HIV Progression in
Naive HIV Patients
AB - Background: Herpes simplex virus type 2 (HSV-2) is a common infection in human
immunodeficiency virus (HIV) patients and may accelerate HIV progression by
rising HIV viral load and decreasing CD4 count. However, the available data
regarding the influence of HSV-2 seropositivity on HIV progression in HIV
individuals are inconclusive. Therefore, we aimed to determine HSV-2
seroprevalence in naive HIV patients and normal controls and also investigate the
relation of HIV viral load and CD4 count with HSV-2 seropositivity. Subsequently,
we investigated the association of HSV-2 serostatus with changing in CD4 count
and HIV viral load in our subjects, after one year follow-up. Methods: In this
study, 116 naive HIV patients and 85 healthy controls from Tehran, Iran were
enrolled. HSV-2 IgG antibody was detected by ELISA. CD4 count was determined by
flowcytometry, and serum HIV RNA copy numbers were determined using real-time
PCR. Results: The prevalence of HSV-2 IgG was 18.1% in naive HIV patients and 0%
in the control group (P=0.000). HSV-2 seroconversion was observed in 2.43% of HIV
patients after one year. There was no significant difference regarding HSV-2
serostatus with CD4 count and HIV RNA viral load in our study cohort at baseline
and after one year. Conclusion: Our results revealed that the prevalence and
incidence of HSV-2 infection are low in our HIV cases, and it is negligible in
control group. However, it seems that HIV/HSV2 co-infection has no role on HIV
infection acceleration.
PMID- 28688380
TI - Coupled-cluster based approach for core-level states in condensed phase: Theory
and application to different protonated forms of aqueous glycine.
AB - A theoretical approach for calculating core-level states in condensed phase is
presented. The approach is based on the equation-of-motion coupled-cluster (EOM
CC) theory and effective fragment potential (EFP) method. By introducing
approximate treatment of double excitations in the EOM-CC with single and double
substitutions ansatz, we address poor convergence issues that are encountered for
the core-level states and significantly reduce computational costs. While the
approximations introduce relatively large errors in the absolute values of
transition energies, the errors are systematic. Consequently, chemical shifts,
changes in ionization energies relative to reference systems, are reproduced
reasonably well. By using different protonation forms of solvated glycine as a
benchmark system, we show that our protocol is capable of reproducing the
experimental chemical shifts with a quantitative accuracy. The results
demonstrate that chemical shifts are very sensitive to the solvent interactions
and that explicit treatment of a solvent, such as within EFP framework, is
essential for achieving quantitative accuracy.
PMID- 28688379
TI - Formaldehyde roaming dynamics: Comparison of quasi-classical trajectory
calculations and experiments.
AB - The photodissociation dynamics of roaming in formaldehyde are studied by
comparing quasi-classical trajectory calculations performed on a new potential
energy surface (PES) to new and detailed experimental results detailing the CO +
H2 product state distributions and their correlations. The new PES proves to be a
significant improvement over the past one, now more than a decade old. The new
experiments probe both the CO and H2 products of the formaldehyde dissociation.
The experimental and trajectory data offer unprecedented detail about the
correlations between internal states of the CO and H2 dissociation products as
well as information on how these distributions are different for the roaming and
transition-state pathways. The data investigated include, for dissociation on the
formaldehyde 2143 band, (a) the speed distributions for individual
vibrational/rotational states of the CO products, providing information about the
correlated internal energy distributions of the H2 product, and (b) the
rotational and vibrational distributions for the CO and H2 products as well as
the contributions to each from both the transition state and roaming channels.
The agreement between the trajectory and experimental data is quite satisfactory,
although minor differences are noted. The general agreement provides support for
future use of the experimental techniques and the new PES in understanding the
dynamics of photodissociative processes.
PMID- 28688381
TI - Zeroth order regular approximation approach to electric dipole moment
interactions of the electron.
AB - A quasi-relativistic two-component approach for an efficient calculation of P,T
odd interactions caused by a permanent electric dipole moment of the electron
(eEDM) is presented. The approach uses a (two-component) complex generalized
Hartree-Fock and a complex generalized Kohn-Sham scheme within the zeroth order
regular approximation. In applications to select heavy-elemental polar diatomic
molecular radicals, which are promising candidates for an eEDM experiment, the
method is compared to relativistic four-component electron-correlation
calculations and confirms values for the effective electric field acting on the
unpaired electron for RaF, BaF, YbF, and HgF. The calculations show that purely
relativistic effects, involving only the lower component of the Dirac bi-spinor,
are well described by treating only the upper component explicitly.
PMID- 28688382
TI - A critical evaluation of perturbation theories by Monte Carlo simulation of the
first four perturbation terms in a Helmholtz energy expansion for the Lennard
Jones fluid.
AB - The Helmholtz energy of a fluid interacting by a Lennard-Jones pair potential is
expanded in a perturbation series. Both the methods of Barker-Henderson (BH) and
of Weeks-Chandler-Andersen (WCA) are evaluated for the division of the
intermolecular potential into reference and perturbation parts. The first four
perturbation terms are evaluated for various densities and temperatures (in the
ranges rho*=0-1.5 and T*=0.5-12) using Monte Carlo simulations in the canonical
ensemble. The simulation results are used to test several approximate theoretical
methods for describing perturbation terms or for developing an approximate
infinite order perturbation series. Additionally, the simulations serve as a
basis for developing fully analytical third order BH and WCA perturbation
theories. The development of analytical theories allows (1) a careful comparison
between the BH and WCA formalisms, and (2) a systematic examination of the effect
of higher-order perturbation terms on calculated thermodynamic properties of
fluids. Properties included in the comparison are supercritical thermodynamic
properties (pressure, internal energy, and chemical potential), vapor-liquid
phase equilibria, second virial coefficients, and heat capacities. For all
properties studied, we find a systematically improved description upon using a
higher-order perturbation theory. A result of particular relevance is that a
third order perturbation theory is capable of providing a quantitative
description of second virial coefficients to temperatures as low as the triple
point of the Lennard-Jones fluid. We find no reason to prefer the WCA formalism
over the BH formalism.
PMID- 28688383
TI - The photodissociation of N,N-dimethylnitrosamine at 355 nm: The effect of excited
state conformational changes on product vector correlations.
AB - In a photodissociation experiment, the dynamics associated with creating reaction
products with specific energies can be understood by a study of the product
vector correlations. Upon excitation to the S1 state, N,N-dimethylnitrosamine
(DMN) undergoes an excited-state geometry change from planar to pyramidal around
the central N. The significant geometry change affects the vector correlations in
the photoproducts. Using polarized lasers for 355 nm photodissociation of DMN and
for NO photoproduct excitation in a velocity-mapped ion imaging apparatus reveals
new vector correlation details among the parent transition dipole (MU),
photofragment velocity (v), and photofragment angular momentum (j). The
dissociation of DMN displays some MU-v correlation [beta02(20)=-0.2], little MU-j
correlation [beta02(02)~0], and, surprisingly, a v-j [beta00(22)] correlation
that depends on the NO lambda doublet probed. The results point to the importance
of the initial excited-state conformational change and uncover the presence of
two photolysis channels.
PMID- 28688384
TI - Prompt release of O 1D products upon UV excitation of CH2OO Criegee
intermediates.
AB - Velocity map imaging has been used to characterize the angular and velocity
distributions of O 1D photofragments arising from UV excitation of the simplest
Criegee intermediate CH2OO in the long wavelength tail region (364 to 417 nm) of
the B1A'-X1A' spectrum. The O 1D images exhibit anisotropic angular distributions
indicative of rapid dissociation to H2CO X1A1 + O 1D products, which occurs
faster than the rotational period (ps) of CH2OO. As a result, the broad
oscillatory structure reported previously in the long wavelength region of the UV
absorption spectrum is attributed to short-lived resonances associated with the
excited B1A' state of CH2OO, which decay by nonadiabatic coupling to repulsive
singlet states. The total kinetic energy distributions show that nearly half of
the available energy, on average, is partitioned to product translation. The
balance results in significant internal excitation of the H2CO co-fragments. The
product anisotropy and energy partitioning are unchanged across the UV spectrum
and consistent with previously reported experimental and theoretical findings of
the CH2OO B-X transition moment and dissociation energy to H2CO X1A1 + O 1D
products.
PMID- 28688385
TI - Circular dichroism in photoelectron images from aligned nitric oxide molecules.
AB - We have used velocity map photoelectron imaging to study circular dichroism of
the photoelectron angular distributions (PADs) of nitric oxide following two
color resonance-enhanced two-photon ionization via selected rotational levels of
the A 2Sigma+, v'=0 state. By using a circularly polarized pump beam and a
counter-propagating, circularly polarized probe beam, cylindrical symmetry is
preserved in the ionization process, and the images can be reconstructed using
standard algorithms. The velocity map imaging set up enables individual ion
rotational states to be resolved with excellent collection efficiency, rendering
the measurements considerably simpler to perform than previous measurements
conducted with a conventional photoelectron spectrometer. The results demonstrate
that circular dichroism is observed even when cylindrical symmetry is maintained,
and serve as a reminder that dichroism is a general feature of the multiphoton
ionization of atoms and molecules. The observed PADs are in good agreement with
calculations based on parameters extracted from previous experimental results
obtained by using a time-of-flight electron spectrometer.
PMID- 28688386
TI - Reaction dynamics of Al + CO2 -> AlO + CO studied by a crossed-beam velocity map
imaging technique.
AB - The oxidation reaction of a gas-phase aluminum atom by a carbon dioxide molecule
was studied by employing a crossed-beam technique at two collision energies: 27.9
and 52.8 kJ/mol. A (1 + 1) resonance-enhanced multiphoton ionization via the
D2Sigma+-X2Sigma+ transition of AlO was applied to ionize the product. For
several rotational levels of AlO in the vibrational ground state, time-sliced ion
images were measured for the first time, and the angular-kinetic energy
distributions were determined. All angular distributions showed forward and
backward peaks; the forward peaks were more pronounced than the backward ones at
the two collision energies. The product kinetic energy showed rather narrow
distributions whose peaks appeared at near to the highest limit estimated from
the available energies. The rotational distributions of the counter product CO,
derived from the kinetic energy distributions, suggested that only a limited
number of rotational states were formed and that a small amount of energies go
into this mode. These results suggested that the reaction proceeds via a short
lived intermediate in which the O-C-O keeps a nearly linear structure.
PMID- 28688387
TI - Ultraviolet photochemistry of 2-bromothiophene explored using universal
ionization detection and multi-mass velocity-map imaging with a PImMS2 sensor.
AB - The ultraviolet photochemistry of 2-bromothiophene (C4H3SBr) has been studied
across the wavelength range 265-245 nm using a velocity-map imaging (VMI)
apparatus recently modified for multi-mass imaging and vacuum ultraviolet (VUV,
118.2 nm) universal ionization. At all wavelengths, molecular products arising
from the loss of atomic bromine were found to exhibit recoil velocities and
anisotropies consistent with those reported elsewhere for the Br fragment [J.
Chem. Phys. 142, 224303 (2015)]. Comparison between the momentum distributions of
the Br and C4H3S fragments suggests that bromine is formed primarily in its
ground (2P3/2) spin-orbit state. These distributions match well at high momentum,
but relatively fewer slow moving molecular fragments were detected. This is
explained by the observation of a second substantial ionic product, C3H3+.
Analysis of ion images recorded simultaneously for several ion masses and the
results of high-level ab initio calculations suggest that this fragment ion
arises from dissociative ionization (by the VUV probe laser) of the most
internally excited C4H3S fragments. This study provides an excellent benchmark
for the recently modified VMI instrumentation and offers a powerful demonstration
of the emerging field of multi-mass VMI using event-triggered, high frame-rate
sensors, and universal ionization.
PMID- 28688388
TI - Liberation of H2 from (o-C6H4Me)3P-H(+) + (-)H-B(p-C6F4H)3 ion-pair: A transition
state in the minimum energy path versus the transient species in Born-Oppenheimer
molecular dynamics.
AB - Using Born-Oppenheimer molecular dynamics (BOMD) with density functional theory,
transition-state (TS) calculations, and the quantitative energy decomposition
analysis (EDA), we examined the mechanism of H2-liberation from LB-H(+) + (-)H-LA
ion-pair, 1, in which the Lewis base (LB) is (o-C6H4Me)3P and the Lewis acid (LA)
is B(p-C6F4H)3. BOMD simulations indicate that the path of H2 liberation from the
ion-pair 1 goes via the short-lived transient species, LB?H2?LA, which are
structurally reminiscent of the TS-structure in the minimum-energy-path
describing the reversible reaction between H2 and (o-C6H4Me)3P/B(p-C6F4H)3
frustrated Lewis pair (FLP). With electronic structure calculations performed on
graphics processing units, our BOMD data-set covers more than 1 ns of evolution
of the ion-pair 1 at temperature T ~ 400 K. BOMD simulations produced H2
recombination events with various durations of H2 remaining fully recombined as a
molecule within a LB/LA attractive "pocket"-from very short vibrational-time
scale to time scales in the range of a few hundred femtoseconds. With the help of
perturbational approach to trajectory-propagation over a saddle-area, we directly
examined dynamics of H2-liberation. Using EDA, we elucidated interactions between
the cationic and anionic fragments in the ion-pair 1 and between the molecular
fragments in the TS-structure. We have also considered a model that qualitatively
takes into account the potential energy characteristics of H-H recombination and
H2-release plus inertia of molecular motion of the (o-C6H4Me)3P/B(p-C6F4H)3 FLP.
PMID- 28688389
TI - Elemental and cooperative diffusion in a liquid, supercooled liquid and glass
resolved.
AB - The diffusion mechanisms controlling viscous flow, structural relaxation, liquid
liquid phase separation, crystal nucleation, and crystal growth in multicomponent
glass-forming liquids are of great interest and relevance in physics, chemistry,
materials, and glass science. However, the diffusing entities that control each
of these important dynamic processes are still unknown. The main objective of
this work is to shed some light on this mystery, advancing the knowledge on this
phenomenon. For that matter, we measured the crystal growth rates, the viscosity,
and lead diffusivities in PbSiO3 liquid and glass in a wide temperature range. We
compared our measured values with published data covering 16 orders of magnitude.
We suggest that above a certain temperature range Td (1.2Tg-1.3Tg), crystal
growth and viscous flow are controlled by the diffusion of silicon and lead.
Below this temperature, crystal growth and viscous flow are more sluggish than
the diffusion of silicon and lead. Therefore, Td marks the temperature where
decoupling between the (measured) cationic diffusivity and the effective
diffusivities calculated from viscosity and crystal growth rates occurs. We
reasonably propose that the nature or size of the diffusional entities
controlling viscous flow and crystal growth below Td is quite different; the
slowest is the one controlling viscous flow, but both processes require
cooperative movements of some larger structural units rather than jumps of only
one or a few isolated atoms.
PMID- 28688390
TI - On the calculation of resonances by analytic continuation of eigenvalues from the
stabilization graph.
AB - Resonances play a major role in a large variety of fields in physics and
chemistry. Accordingly, there is a growing interest in methods designed to
calculate them. Recently, Landau et al. proposed a new approach to analytically
dilate a single eigenvalue from the stabilization graph into the complex plane.
This approach, termed Resonances Via Pade (RVP), utilizes the Pade approximant
and is based on a unique analysis of the stabilization graph. Yet, analytic
continuation of eigenvalues from the stabilization graph into the complex plane
is not a new idea. In 1975, Jordan suggested an analytic continuation method
based on the branch point structure of the stabilization graph. The method was
later modified by McCurdy and McNutt, and it is still being used today. We refer
to this method as the Truncated Characteristic Polynomial (TCP) method. In this
manuscript, we perform an in-depth comparison between the RVP and the TCP
methods. We demonstrate that while both methods are important and complementary,
the advantage of one method over the other is problem-dependent. Illustrative
examples are provided in the manuscript.
PMID- 28688391
TI - CRF-PEPICO: Double velocity map imaging photoelectron photoion coincidence
spectroscopy for reaction kinetics studies.
AB - Photoelectron photoion coincidence (PEPICO) spectroscopy could become a powerful
tool for the time-resolved study of multi-channel gas phase chemical reactions.
Toward this goal, we have designed and tested electron and ion optics that form
the core of a new PEPICO spectrometer, utilizing simultaneous velocity map
imaging for both cations and electrons, while also achieving good cation mass
resolution through space focusing. These optics are combined with a side-sampled,
slow-flow chemical reactor for photolytic initiation of gas-phase chemical
reactions. Together with a recent advance that dramatically increases the dynamic
range in PEPICO spectroscopy [D. L. Osborn et al., J. Chem. Phys. 145, 164202
(2016)], the design described here demonstrates a complete prototype spectrometer
and reactor interface to carry out time-resolved experiments. Combining dual
velocity map imaging with cation space focusing yields tightly focused photoion
images for translationally cold neutrals, while offering good mass resolution for
thermal samples as well. The flexible optics design incorporates linear electric
fields in the ionization region, surrounded by dual curved electric fields for
velocity map imaging of ions and electrons. Furthermore, the design allows for a
long extraction stage, which makes this the first PEPICO experiment to combine
ion imaging with the unimolecular dissociation rate constant measurements of
cations to detect and account for kinetic shifts. Four examples are shown to
illustrate some capabilities of this new design. We recorded the threshold
photoelectron spectrum of the propargyl and the iodomethyl radicals. While the
former agrees well with a literature threshold photoelectron spectrum, we have
succeeded in resolving the previously unobserved vibrational structure in the
latter. We have also measured the bimolecular rate constant of the CH2I + O2
reaction and observed its product, the smallest Criegee intermediate, CH2OO.
Finally, the second dissociative photoionization step of iodocyclohexane ions,
the loss of ethylene from the cyclohexyl cation, is slow at threshold, as
illustrated by the asymmetric threshold photoionization time-of-flight
distributions.
PMID- 28688392
TI - Pair-correlated stereodynamics for diatom-diatom rotational energy transfer:
NO(A2Sigma+) + N2.
AB - We have performed a crossed molecular beam velocity-map ion imaging study of
state-to-state rotational energy transfer of NO(A2Sigma+, v = 0, N = 0, j = 0.5)
in collisions with N2 and have measured rotational angular momentum polarization
dependent images of product NO(A) rotational levels N' = 3 and 5-11 for
collisions at an average energy of 797 cm-1. We present an extension of our
previously published [T. F. M. Luxford et al., J. Chem. Phys. 145, 174 304
(2016)] image analysis which includes the effect of rotational excitation of the
unobserved collision partner and critically evaluate this methodology. We report
differential cross sections and angle-resolved angular momentum alignment moments
for NO(A) levels N' = 3 and 5-11 as a function of the rotational excitation of
the coincident N2 partner. The scattering dynamics of NO(A) + N2 share
similarities with those previously reported for NO(A) + Ne and Ar, although with
detailed differences. We use comparison of the measurements reported here to the
scattering of NO(A) with Ne, and the known NO(A)-Ne potential energy surface, to
draw conclusions about the previously unknown NO(A)-N2 potential.
PMID- 28688393
TI - A hybrid memory kernel approach for condensed phase non-adiabatic dynamics.
AB - The spin-boson model is a simplified Hamiltonian often used to study non
adiabatic dynamics in large condensed phase systems, even though it has not been
solved in a fully analytic fashion. Herein, we present an exact analytic
expression for the dynamics of the spin-boson model in the infinitely slow-bath
limit and generalize it to approximate dynamics for faster baths. We achieve the
latter by developing a hybrid approach that combines the exact slow-bath result
with the popular non-interacting blip approximation (NIBA) method to generate a
memory kernel that is formally exact to second-order in the diabatic coupling but
also contains higher-order contributions approximated from the second-order term
alone. This kernel has the same computational complexity as the NIBA, but is
found to yield dramatically superior dynamics in regimes where the NIBA breaks
down-such as systems with large diabatic coupling or energy bias. This indicates
that this hybrid approach could be used to cheaply incorporate higher-order
effects into second-order methods and could potentially be generalized to develop
alternate kernel resummation schemes.
PMID- 28688394
TI - Stereodirectional images of molecules oriented by a variable-voltage hexapolar
field: Fragmentation channels of 2-bromobutane electronically excited at two
photolysis wavelengths.
AB - The asymmetric-top molecule 2-bromobutane is oriented by means of a hexapole
state selector; the angular distribution of the bromine atom photofragment, for
the two fine-structure components, is acquired by velocity-map ion imaging. The
molecular beam, spatially oriented along the time-of-flight axis, is intersected
with a linearly polarized laser, whose polarization is tilted by 45 degrees with
respect to the detector surface. To obtain the mixing ratio of the perpendicular
and parallel transitions, the fragment ion images and angular distributions can
be appropriately simulated to give insight on the population mechanism of the
specific electronic state involved at each selected excitation wavelength. The
photofragment images obtained at 238.6 nm yielded an asymmetry factor beta1 of
0.67, indicative of the extent of molecular orientation, and an anisotropy
parameter beta2 of 1.03, which is a signature of a prevailing parallel transition
along the C-Br axis. When the photolysis wavelength is tuned to 254.1 nm, the
corresponding angular distribution is less asymmetric (beta1 = 0.24) and the
obtained small value beta2 = 0.12 is a characteristic of a predominantly
perpendicular transition. The photofragment angular distributions are also
affected by hexapole voltage, especially regarding the asymmetry factor, and this
aspect provides information on the effect of molecular orientation.
PMID- 28688395
TI - Assessing the accuracy of integral equation theories for nano-sized hydrophobic
solutes in water.
AB - Integral equation theories provide an efficient route for computing the solvation
free energy (SFE) of molecular systems in water. The accuracy of those theories
is usually tested against small molecules via comparison of SFE with reference
data. However, tests against larger molecules in the nanometer regime are scarce
in literature despite recent applications to such systems. Here, we thus study
the accuracy and validity of a commonly used integral equation theory, namely, a
three-dimensional reference interaction site model (3D-RISM), by considering the
following problems: (1) solvation of a small to large Lennard-Jones particle, (2)
binding of planar hydrophobic systems with varying size and hydrophobicity, and
(3) self-assembly of amphiphilic molecules into a nanocapsule. The energy
representation method is also utilized for comparison. The results show that the
3D-RISM method works successfully for small molecules, while the accuracy
degrades systematically with system size and hydrophobicity. The size-dependent
error in SFE does not cancel adequately between two solute configurations,
resulting in a substantial error in the free energy difference. It is also shown
that the free energy profiles for hydrophobic association exhibit a fictitious
high-energy barrier, suggesting that care must be taken for studying such
systems. The numerical difficulties observed above are discussed based on the
relation between hypernetted-chain approximation, classical density functional
theory with quadratic expansion, and the size-dependent error arising from the
cavity region of the system.
PMID- 28688396
TI - Experimental and theoretical investigations of H2O-Ar.
AB - We have used continuous-wave cavity ring-down spectroscopy to record the spectrum
of H2O-Ar in the 2OH excitation range of H2O. 24 sub-bands have been observed.
Their rotational structure (Trot = 12 K) is analyzed and the lines are fitted
separately for ortho and para species together with microwave and far infrared
data from the literature, with a unitless standard deviation sigma=0.98 and 1.31,
respectively. Their vibrational analysis is supported by a theoretical input
based on an intramolecular potential energy surface obtained through ab initio
calculations and computation of the rotational energy of sub-states of the
complex with the water monomer in excited vibrational states up to the first
hexad. For the ground and (010) vibrational states, the theoretical results agree
well with experimental energies and rotational constants in the literature. For
the excited vibrational states of the first hexad, they guided the assignment of
the observed sub-bands. The upper state vibrational predissociation lifetime is
estimated to be 3 ns from observed spectral linewidths.
PMID- 28688397
TI - Femtosecond dynamics of the 2-methylallyl radical: A computational and
experimental study.
AB - We investigate the photodynamics of the 2-methylallyl radical by femtosecond time
resolved photoelectron imaging. The experiments are accompanied by field-induced
surface hopping dynamics calculations and the simulation of time-resolved
photoelectron intensities and anisotropies, giving insight into the
photochemistry and nonradiative relaxation of the radical. 2-methylallyl is
excited at 236 nm, 238 nm, and 240.6 nm into a 3p Rydberg state, and the
subsequent dynamics is probed by multiphoton ionization using photons of 800 nm.
The photoelectron image exhibits a prominent band with considerable anisotropy,
which is compatible with the result of theory. The simulations show that the
initially excited 3p state is rapidly depopulated to a 3s Rydberg state, from
which photoelectrons of high anisotropy are produced. The 3s state then decays
within several 100 fs to the D1 (npi) state, followed by the deactivation of the
D1 to the electronic ground state on the ps time scale.
PMID- 28688398
TI - Intermediate state dependence of the photoelectron circular dichroism of fenchone
observed via femtosecond resonance-enhanced multi-photon ionization.
AB - The intermediate state dependence of photoelectron circular dichroism (PECD) in
resonance-enhanced multi-photon ionization of fenchone in the gas phase is
experimentally studied. By scanning the excitation wavelength from 359 to 431 nm,
we simultaneously excite up to three electronically distinct resonances. In the
PECD experiment performed with a broadband femtosecond laser, their respective
contributions to the photoelectron spectrum can be resolved. High-resolution
spectroscopy allows us to identify two of the resonances as belonging to the B-
and C-bands, which involve excitation to states with 3s and 3p Rydberg character,
respectively. We observe a sign change in the PECD signal, depending on which
electronic state is used as an intermediate, and are able to identify two
differently behaving contributions within the C-band. Scanning the laser
wavelength reveals a decrease of PECD magnitude with increasing photoelectron
energy for the 3s state. Combining the results of high-resolution spectroscopy
and femtosecond experiment, the adiabatic ionization potential of fenchone is
determined to be IPaFen=(8.49+/-0.06) eV.
PMID- 28688399
TI - A "circularisation" method to repair deformations and determine the centre of
velocity map images.
AB - A problem besetting the analysis of velocity map images, particularly those of
photoelectrons, is the presence of distortions that cause the features in the
image to deviate from circularity, leading to a loss of resolution in the
spectrum extracted. A method is presented to repair such distortions based on
fitting the angular behaviour of each of the ring structures to a trigonometric
expansion. The repair function allows the intensity at any value of radius and
angle to be mapped to a new position that removes the distortion and returns the
features to circular. While the method relies on the analysis of the structure in
an image, it could also be applied to determine the "repair function" using a
calibration image (or series of images) for the experiment. Once the image has
been circularised it can be processed by any of the approaches that have been
developed for that purpose. The analysis also enables the image centre to be
determined with high accuracy. The fitting method utilises an inverse Abel
transformation of the image in polar coordinates as a means to reshape the image
into a series of spectral features in order to determine the radial position of
features at each angle. Although the velocity distribution is not in general
spherically symmetric and so this is not a mathematically correct means to
extract the velocity distribution, the feature positions are accurately
reproduced in the resulting spectrum while the intensity and anisotropy
parameters can be remarkably close to those obtained using the proper inverse
Abel transformation of the image.
PMID- 28688400
TI - Strongly aligned molecules inside helium droplets in the near-adiabatic regime.
AB - Iodine (I2) molecules embedded in He nanodroplets are aligned by a 160 ps long
laser pulse. The highest degree of alignment, occurring at the peak of the pulse
and quantified by ?cos2??2D?, is measured as a function of the laser intensity.
The results are well described by ?cos2??2D? calculated for a gas of isolated
molecules each with an effective rotational constant of 0.6 times the gas-phase
value and at a temperature of 0.4 K. Theoretical analysis using the angulon
quasiparticle to describe rotating molecules in superfluid helium rationalizes
why the alignment mechanism is similar to that of isolated molecules with an
effective rotational constant. A major advantage of molecules in He droplets is
that their 0.4 K temperature leads to stronger alignment than what can generally
be achieved for gas phase molecules-here demonstrated by a direct comparison of
the droplet results to measurements on a ~1 K supersonic beam of isolated
molecules. This point is further illustrated for a more complex system by
measurements on 1,4-diiodobenzene and 1,4-dibromobenzene. For all three molecular
species studied, the highest values of ?cos2??2D? achieved in He droplets exceed
0.96.
PMID- 28688401
TI - Probing photoisomerization processes by means of multi-dimensional electronic
spectroscopy: The multi-state quantum hierarchical Fokker-Planck equation
approach.
AB - Photoisomerization in a system with multiple electronic states and anharmonic
potential surfaces in a dissipative environment is investigated using a rigorous
numerical method employing quantum hierarchical Fokker-Planck equations (QHFPEs)
for multi-state systems. We have developed a computer code incorporating QHFPE
for general-purpose computing on graphics processing units that can treat multi
state systems in phase space with any strength of diabatic coupling of electronic
states under non-perturbative and non-Markovian system-bath interactions. This
approach facilitates the calculation of both linear and nonlinear spectra. We
computed Wigner distributions for excited, ground, and coherent states. We then
investigated excited state dynamics involving transitions among these states by
analyzing linear absorption and transient absorption processes and multi
dimensional electronic spectra with various values of heat bath parameters. Our
results provide predictions for spectroscopic measurements of photoisomerization
dynamics. The motion of excitation and ground state wavepackets and their
coherence involved in the photoisomerization were observed as the profiles of
positive and negative peaks of two-dimensional spectra.
PMID- 28688403
TI - Photofragmentation dynamics and dissociation energies of MoO and CrO.
AB - Neutral metal-containing molecules and clusters present a particular challenge to
velocity map imaging techniques. Common methods of choice for producing such
species-such as laser ablation or magnetron sputtering-typically generate a wide
variety of metal-containing species and, without the possibility of mass
selection, even determining the identity of the dissociating moiety can be
challenging. In recent years, we have developed a velocity map imaging
spectrometer equipped with a laser ablation source explicitly for studying
neutral metal-containing species. Here, we report the results of velocity map
imaging photofragmentation studies of MoO and CrO. In both cases, dissociation at
the two- and three-photon level leads to fragmentation into a range of product
channels, some of which can be confidently assigned to particular Mo* (Cr*) and O
atom quantum states. Analysis of the kinetic energy release spectra as a function
of photon energy allows precise determination of the ground state dissociation
energies of MoO (=44 064 +/- 133 cm-1) and CrO (=37 197 +/- 78 cm-1),
respectively.
PMID- 28688402
TI - Temperature dependence of the photodissociation of CO2 from high vibrational
levels: 205-230 nm imaging studies of CO(X1Sigma+) and O(3P, 1D) products.
AB - The 205-230 nm photodissociation of vibrationally excited CO2 at temperatures up
to 1800 K was studied using Resonance Enhanced Multiphoton Ionization (REMPI) and
time-sliced Velocity Map Imaging (VMI). CO2 molecules seeded in He were heated in
an SiC tube attached to a pulsed valve and supersonically expanded to create a
molecular beam of rotationally cooled but vibrationally hot CO2.
Photodissociation was observed from vibrationally excited CO2 with internal
energies up to about 20 000 cm-1, and CO(X1Sigma+), O(3P), and O(1D) products
were detected by REMPI. The large enhancement in the absorption cross section
with increasing CO2 vibrational excitation made this investigation feasible. The
internal energies of heated CO2 molecules that absorbed 230 nm radiation were
estimated from the kinetic energy release (KER) distributions of CO(X1Sigma+)
products in v" = 0. At 230 nm, CO2 needs to have at least 4000 cm-1 of
rovibrational energy to absorb the UV radiation and produce CO(X1Sigma+) + O(3P).
CO2 internal energies in excess of 16 000 cm-1 were confirmed by observing O(1D)
products. It is likely that initial absorption from levels with high bending
excitation accesses both the A1B2 and B1A2 states, explaining the nearly
isotropic angular distributions of the products. CO(X1Sigma+) product internal
energies were estimated from REMPI spectroscopy, and the KER distributions of the
CO(X1Sigma+), O(3P), and O(1D) products were obtained by VMI. The CO product
internal energy distributions change with increasing CO2 temperature, suggesting
that more than one dynamical pathway is involved when the internal energy of CO2
(and the corresponding available energy) increases. The KER distributions of
O(1D) and O(3P) show broad internal energy distributions in the CO(X1Sigma+)
cofragment, extending up to the maximum allowed by energy but peaking at low KER
values. Although not all the observations can be explained at this time, with the
aid of available theoretical studies of CO2 VUV photodissociation and O + CO
recombination, it is proposed that following UV absorption, the two lowest lying
triplet states, a3B2 and b3A2, and the ground electronic state are involved in
the dynamical pathways that lead to product formation.
PMID- 28688404
TI - Melting of superheated molecular crystals.
AB - Melting dynamics of micrometer scale, polycrystalline samples of isobutane,
dimethyl ether, methyl benzene, and 2-propanol were investigated by fast scanning
calorimetry. When films are superheated with rates in excess of 105 K s-1, the
melting process follows zero-order, Arrhenius-like kinetics until approximately
half of the sample has transformed. Such kinetics strongly imply that melting
progresses into the bulk via a rapidly moving solid-liquid interface that is
likely to originate at the sample's surface. Remarkably, the apparent activation
energies for the phase transformation are large; all exceed the enthalpy of
vaporization of each compound and some exceed it by an order of magnitude. In
fact, we find that the crystalline melting kinetics are comparable to the
kinetics of dielectric alpha-relaxation in deeply supercooled liquids. Based on
these observations, we conclude that the rate of non-isothermal melting for
superheated, low-molecular-weight crystals is limited by constituent diffusion
into an abnormally dense, glass-like, non-crystalline phase.
PMID- 28688405
TI - Ion-ion coincidence imaging at high event rate using an in-vacuum pixel detector.
AB - A new ion-ion coincidence imaging spectrometer based on a pixelated complementary
metal-oxide-semiconductor detector has been developed for the investigation of
molecular ionization and fragmentation processes in strong laser fields. Used as
a part of a velocity map imaging spectrometer, the detection system is comprised
of a set of microchannel plates and a Timepix detector. A fast time-to-digital
converter (TDC) is used to enhance the ion time-of-flight resolution by
correlating timestamps registered separately by the Timepix detector and the TDC.
In addition, sub-pixel spatial resolution (<6 MUm) is achieved by the use of a
center-of-mass centroiding algorithm. This performance is achieved while
retaining a high event rate (104 per s). The spectrometer was characterized and
used in a proof-of-principle experiment on strong field dissociative double
ionization of carbon dioxide molecules (CO2), using a 400 kHz repetition rate
laser system. The experimental results demonstrate that the spectrometer can
detect multiple ions in coincidence, making it a valuable tool for studying the
fragmentation dynamics of molecules in strong laser fields.
PMID- 28688406
TI - Imaging multiphoton ionization and dissociation of rotationally warm CO via the
B+Sigma1 and EPi1 electronic states.
AB - Pathways for formation of C+ and O+ ions when applying (2 + 1) resonance enhanced
multiphoton ionization (REMPI) of CO via the B1Sigma+ and E1Pi electronic states
are characterized with the velocity map imaging technique. By employing an
unskimmed pulsed valve, it was possible to obtain sharp images for a wide range
of initial CO J-states. Most of the atomic ion production pathways could be
assigned as one- or two-photon dissociation of a series of vibrational levels of
the CO+ X2Sigma+ and A2Pi states. Large enhancements in dissociation of
particular CO+ vibrational states in these progressions could be accurately
assigned to accidental resonances of the REMPI laser with CO+ X2Sigma+-B2Sigma+
transitions.
PMID- 28688407
TI - Finite slice analysis (FINA)-A general reconstruction method for velocity mapped
and time-sliced ion imaging.
AB - Since the advent of ion imaging, one of the key issues in the field has been
creating methods to reconstruct the initial 3D distribution of particles from its
2D projection. This has led to the development of a number of different numerical
methods and fitting techniques to solve this fundamental issue in imaging. In
recent years, slice-imaging methods have been developed that permit direct
recording of the 3D distribution, i.e., a thin slice of the recoiling fragment
distribution. However, in practice, most slice imaging experiments achieve a
velocity slice width of around 10%-25% around the center of the distribution.
This still carries significant out-of-plane elements that can blur the spectrum,
lose fine resolution, and underestimate the contribution from slow recoiling
products. To overcome these limitations, we developed a new numerical method to
remove these out-of-plane elements from a sliced image. The finite sliced
analysis method models the off-axis elements of the 3D particle distribution
through the use of radial basis functions. Once applied, the method reconstructs
the underlying central slice of the 3D particle distribution. The approach may be
applied to arbitrarily sliced or unsliced data and has the further advantage that
it neither requires nor enforces full cylindrical symmetry of the data. We
demonstrate this reconstruction approach with a broad range of synthetic and
experimental data that, at the same time, allows us to examine the impact of
finite slicing on the recovered distributions in detail.
PMID- 28688408
TI - Diffusion of small particles in polymer films.
AB - The motion of small probe molecules in a two-dimensional system containing frozen
polymer chains was studied by means of Monte Carlo simulations. The model
macromolecules were coarse-grained and restricted to vertices of a triangular
lattice. The cooperative motion algorithm was used to generate representative
configurations of macromolecular systems of different polymer concentrations. The
remaining unoccupied lattice sites of the system were filled with small
molecules. The structure of the polymer film, especially near the percolation
threshold, was determined. The dynamic lattice liquid algorithm was then employed
for studies of the dynamics of small objects in the polymer matrix. The influence
of chain length and polymer concentration on the mobility and the character of
motion of small molecules were studied. Short- and long-time dynamic behaviors of
solvent molecules were also described. Conditions of anomalous diffusions'
appearance in such systems are discussed. The influence of the structure of the
matrix of obstacles on the molecular transport was discussed.
PMID- 28688409
TI - Imaging diffraction oscillations for inelastic collisions of NO radicals with He
and D2.
AB - We present state-to-state differential cross sections for collisions of NO
molecules (X2Pi1/2,j=1/2,f) with He atoms and ortho-D2 (j = 0) molecules as a
function of collision energy. A high angular resolution obtained using the
combination of Stark deceleration and velocity map imaging allows for the
observation of diffraction oscillations in the angular scattering distributions.
Differences in the differential cross sections and, in particular, differences in
the angular spacing between individual diffraction peaks are observed. Since the
masses of D2 and He are almost equal and since D2(j = 0) may be considered as a
pseudo-atom, these differences directly reflect the larger size of D2 as compared
to He. The observations are in excellent agreement with the cross sections
obtained from quantum close-coupling scattering calculations based on accurate ab
initio NO-He and NO-D2 potential energy surfaces. For the latter, we calculated a
new NO-D2 potential energy surface.
PMID- 28688410
TI - A new electron-ion coincidence 3D momentum-imaging method and its application in
probing strong field dynamics of 2-phenylethyl-N, N-dimethylamine.
AB - We report the development of a new three-dimensional (3D) momentum-imaging setup
based on conventional velocity map imaging to achieve the coincidence measurement
of photoelectrons and photo-ions. This setup uses only one imaging detector
(microchannel plates (MCP)/phosphor screen) but the voltages on electrodes are
pulsed to push both electrons and ions toward the same detector. The ion-electron
coincidence is achieved using two cameras to capture images of ions and electrons
separately. The time-of-flight of ions and electrons are read out from MCP using
a digitizer. We demonstrate this new system by studying the dissociative single
and double ionization of PENNA (2-phenylethyl-N,N-dimethylamine). We further show
that the camera-based 3D imaging system can operate at 10 kHz repetition rate.
PMID- 28688411
TI - Ion and velocity map imaging for surface dynamics and kinetics.
AB - We describe a new instrument that uses ion imaging to study molecular beam
surface scattering and surface desorption kinetics, allowing independent
determination of both residence times on the surface and scattering velocities of
desorbing molecules. This instrument thus provides the capability to derive true
kinetic traces, i.e., product flux versus residence time, and allows dramatically
accelerated data acquisition compared to previous molecular beam kinetics
methods. The experiment exploits non-resonant multiphoton ionization in the near
IR using a powerful 150-fs laser pulse, making detection more general than
previous experiments using resonance enhanced multiphoton ionization. We
demonstrate the capabilities of the new instrument by examining the desorption
kinetics of CO on Pd(111) and Pt(111) and obtain both pre-exponential factors and
activation energies of desorption. We also show that the new approach is
compatible with velocity map imaging.
PMID- 28688412
TI - Conformation-selective resonant photoelectron imaging from dipole-bound states of
cold 3-hydroxyphenoxide.
AB - We report a photoelectron imaging and photodetachment study of cryogenically
cooled 3-hydroxyphenoxide (3HOP) anions, m-HO(C6H4)O-. In a previous preliminary
study, two conformations of the cold 3HOP anions with different dipole bound
states were observed [D. L. Huang et al., J. Phys. Chem. Lett. 6, 2153 (2015)].
Five near-threshold vibrational resonances were revealed in the photodetachment
spectrum from the dipole-bound excited states of the two conformations. Here, we
report a more extensive investigation of the two conformers with observation of
thirty above-threshold vibrational resonances in a wide spectral range between 18
850 and 19 920 cm-1 (~1000 cm-1 above the detachment thresholds). By tuning the
detachment laser to the vibrational resonances in the photodetachment spectrum,
high-resolution conformation-selective resonant photoelectron images are
obtained. Using information of the autodetachment channels and theoretical
vibrational frequencies, we are able to assign the resonant peaks in the
photodetachment spectrum: seventeen are assigned to vibrational levels of anti
3HOP, eight to syn-3HOP, and five to overlapping vibrational levels of both
conformers. From the photodetachment spectrum and the conformation-selective
resonant photoelectron spectra, we have obtained fourteen fundamental vibrational
frequencies for the neutral syn- and anti-m-HO(C6H4)O? radicals. The possibility
to produce conformation-selected neutral beams using resonant photodetachment via
dipole-bound excited states of anions is discussed.
PMID- 28688413
TI - A compact design for velocity-map imaging of energetic electrons and ions.
AB - We present a compact design for a velocity-map imaging spectrometer for energetic
electrons and ions. The standard geometry by Eppink and Parker [Rev. Sci.
Instrum. 68, 3477 (1997)] is augmented by just two extended electrodes so as to
realize an additional einzel lens. In this way, for a maximum electrode voltage
of 7 kV, we experimentally demonstrate imaging of electrons with energies up to
65 eV. Simulations show that energy acceptances ?270 and ?1200 eV with an energy
resolution DeltaE/E?5% are achievable for electrode voltages <=20 kV when using
diameters of the position-sensitive detector of 42 and 78 mm, respectively.
PMID- 28688414
TI - Photofragmentation dynamics of N,N-dimethylformamide following excitation at 193
nm.
AB - N,N-dimethylformamide, HCON(CH3)2, is a useful model compound for investigating
the peptide bond photofragmentation dynamics. We report data from a comprehensive
experimental and theoretical study into the photofragmentation dynamics of N,N
dimethylformamide in the gas phase at 193 nm. Through a combination of velocity
map imaging and hydrogen atom Rydberg tagging photofragment translational
spectroscopy we have identified two primary fragmentation channels, namely,
fission of the N-CO "peptide" bond and N-CH3 bond fission leading to the loss of
CH3. The possible fragmentation channels leading to the observed products are
rationalised with recourse to CASPT2 calculations of the ground and first few
excited-state potential energy curves along the relevant dissociation
coordinates, and the results are compared with the data from previous
experimental and theoretical studies on the same system.
PMID- 28688415
TI - The near ultraviolet photodissociation dynamics of 2- and 3-substituted
thiophenols: Geometric vs. electronic structure effects.
AB - The near ultraviolet spectroscopy and photodissociation dynamics of two families
of asymmetrically substituted thiophenols (2- and 3-YPhSH, with Y = F and Me)
have been investigated experimentally (by H (Rydberg) atom photofragment
translational spectroscopy) and by ab initio electronic structure calculations.
Photoexcitation in all cases populates the 11pipi* and/or 11pisigma* excited
states and results in S-H bond fission. Analyses of the experimentally obtained
total kinetic energy release (TKER) spectra yield the respective parent S-H bond
strengths, estimates of DeltaE(A~-X~), the energy splitting between the ground
(X~) and first excited (A~) states of the resulting 2-(3-)YPhS radicals, and
reveal a clear propensity for excitation of the C-S in-plane bending vibration in
the radical products. The companion theory highlights roles for both geometric
(e.g., steric effects and intramolecular H-bonding) and electronic (i.e., pi
(resonance) and sigma (inductive)) effects in determining the respective parent
minimum energy geometries, and the observed substituent and position-dependent
trends in S-H bond strength and DeltaE(A~-X~). 2-FPhSH shows some clear
spectroscopic and photophysical differences. Intramolecular H-bonding ensures
that most 2-FPhSH molecules exist as the syn rotamer, for which the electronic
structure calculations return a substantial barrier to tunnelling from the
photoexcited 11pipi* state to the 11pisigma* continuum. The 11pipi* <- S0
excitation spectrum of syn-2-FPhSH thus exhibits resolved vibronic structure,
enabling photolysis studies with a greater parent state selectivity. Structure
apparent in the TKER spectrum of the H + 2-FPhS products formed when exciting at
the 11pipi* <- S0 origin is interpreted by assuming unintended photoexcitation of
an overlapping resonance associated with syn-2-FPhSH(v33 = 1) molecules. The
present data offer tantalising hints that such out-of-plane motion influences non
adiabatic coupling in the vicinity of a conical intersection (between the
11pisigma* and ground state potentials at extended S-H bond lengths) and thus the
electronic branching in the eventual radical products.
PMID- 28688416
TI - Publisher's Note: "Thermodynamic formalism for transport coefficients with an
application to the shear modulus and shear viscosity" [J. Chem. Phys. 146, 124130
(2017)].
PMID- 28688417
TI - Slice imaging of the UV photodissociation of CH2BrCl from the maximum of the
first absorption band.
AB - The photodissociation dynamics of bromochloromethane (CH2BrCl) have been
investigated at the maximum of the first absorption band, at the excitation
wavelengths 203 and 210 nm, using the slice imaging technique in combination with
a probe detection of bromine-atom fragments, Br(2P3/2) and Br*(2P1/2), via (2 +
1) resonance enhanced multiphoton ionization. Translational energy distributions
and angular distributions reported for both Br(2P3/2) and Br*(2P1/2) fragments
show two contributions for the Br(2P3/2) channel and a single contribution for
the Br*(2P1/2) channel. High level ab initio calculations have been performed in
order to elucidate the dissociation mechanisms taking place. The computed
absorption spectrum and potential energy curves indicate the main contribution of
the populated 4A", 5A', and 6A' excited states leading to a C-Br cleavage.
Consistently with the results, the single contribution for the Br*(2P1/2) channel
has been attributed to direct dissociation through the 6A' state as well as an
indirect dissociation of the 5A' state requiring a 5A' -> 4A' reverse non
adiabatic crossing. Similarly, a faster contribution for the Br(2P3/2) channel
characterized by a similar energy partitioning and anisotropy than those for the
Br*(2P1/2) channel is assigned to a direct dissociation through the 5A' state,
while the slower component appears to be due to the direct dissociation on the
4A" state.
PMID- 28688418
TI - Photodissociation dynamics of OCS at ~210 nm: The role of c(23A") state.
AB - Photodissociation dynamics of carbonyl sulfide (OCS) in the deep ultraviolet
region is investigated using a time-sliced ion velocity map imaging technique.
The measured total kinetic energy release spectra from the photodissociation of
OCS at ~210 nm shows three dissociation channels to the fragment S(1D2),
corresponding to low, medium, and high kinetic energy release (ET), respectively.
The high ET channel is found to be a new dissociation channel opening with
photolysis wavelength at ~210 nm. Based on the aq(k)(p) polarization parameters
as well as the anisotropy parameters beta determined from the images of S(1D2),
the dissociation of OCS to S(1D2) + CO at 210 nm is concluded to involve a direct
vertical excitation of the triplet c(23A") state from the ground state, followed
by processes as: the low ET component arises from a non-adiabatic transition from
the repulsive A(21A') state to the electronic ground state X(11A'); the medium ET
component arises from a simultaneous excitation to two repulsive excited states;
and the high ET component arises from the intersystem crossing from the triplet
c(23A") state to the repulsive A(21A') state. The present study shows that, due
to the strong spin-orbit coupling between the triplet c(23A") state and the
repulsive A(21A') state, a direct excitation to c(23A") significantly contributes
to the photodissociation dynamics of OCS in the deep-UV region.
PMID- 28688419
TI - Soft X-ray spectroscopy of nanoparticles by velocity map imaging.
AB - Velocity map imaging (VMI), a technique traditionally used to study chemical
dynamics in the gas phase, is applied here to study X-ray photoemission from
aerosol nanoparticles. Soft X-rays from the Advanced Light Source synchrotron,
probe a beam of nanoparticles, and the resulting photoelectrons are velocity
mapped to obtain their kinetic energy distributions. A new design of the VMI
spectrometer is described. The spectrometer is benchmarked by measuring vacuum
ultraviolet photoemission from gas phase xenon and squalene nanoparticles
followed by measurements using soft X-rays. It is demonstrated that the
photoelectron distribution from X-ray irradiated squalene nanoparticles is
dominated by secondary electrons. By scanning the photon energies and measuring
the intensities of these secondary electrons, a near edge X-ray absorption fine
structure (NEXAFS) spectrum is obtained. The NEXAFS technique is used to obtain
spectra of aqueous nanoparticles at the oxygen K edge. By varying the position of
the aqueous nanoparticle beam relative to the incident X-ray beam, evidence is
presented such that the VMI technique allows for NEXAFS spectroscopy of water in
different physical states. Finally, we discuss the possibility of applying VMI
methods to probe liquids and solids via X-ray spectroscopy.
PMID- 28688420
TI - Advantage of spatial map ion imaging in the study of large molecule
photodissociation.
AB - The original ion imaging technique has low velocity resolution, and currently,
photodissociation is mostly investigated using velocity map ion imaging. However,
separating signals from the background (resulting from undissociated excited
parent molecules) is difficult when velocity map ion imaging is used for the
photodissociation of large molecules (number of atoms >= 10). In this study, we
used the photodissociation of phenol at the S1 band origin as an example to
demonstrate how our multimass ion imaging technique, based on modified spatial
map ion imaging, can overcome this difficulty. The photofragment translational
energy distribution obtained when multimass ion imaging was used differed
considerably from that obtained when velocity map ion imaging and Rydberg atom
tagging were used. We used conventional translational spectroscopy as a second
method to further confirm the experimental results, and we conclude that data
should be interpreted carefully when velocity map ion imaging or Rydberg atom
tagging is used in the photodissociation of large molecules. Finally, we propose
a modified velocity map ion imaging technique without the disadvantages of the
current velocity map ion imaging technique.
PMID- 28688421
TI - A simple resonance enhanced laser ionization scheme for CO via the A1Pi state.
AB - We investigate the laser ionization process taking place when the CO molecule is
exposed to vacuum ultraviolet (VUV) radiation resonant with the CO A1Pi(v = 0) <-
X1Sigma+(v = 0) transition around 154 nm, along with the ultraviolet (UV) and
visible (Red) radiation used to generate VUV by four-wave difference-frequency
mixing. By measuring the CO+ ion recoil and a room temperature gas spectrum, it
is possible to assign the ionization process as 1 + 1' + 1'' REMPI where the one
photon steps refer to the VUV, UV, and Red radiation, respectively. Resonance
enhanced ionization of rotational states around J = 12 arise due to the overlap
of the fixed wavelength UV (~250 nm) with the R band-head of a transition
assigned to CO E1Pi(v = 6) <- A1Pi(v = 0) with a term value of 104 787.5 cm-1.
The REMPI process is efficient and polarization sensitive and should be useful in
a wide range of studies involving nascent CO.
PMID- 28688422
TI - An imaging photoelectron-photoion coincidence investigation of homochiral 2R,3R
butanediol clusters.
AB - We report an experimental investigation of homochiral cluster formation in seeded
molecular beam expansions of (2R,3R)-butanediol. Synchrotron radiation vacuum
ultraviolet photoionization measurements have been performed using a double
imaging electron-ion spectrometer in various configurations and modes of
operation. These include measurements of the cluster ion mass spectra, wavelength
scanned ion yields, and threshold electron spectra. Protonated cluster ions
ranging up to n = 7 have been observed and size-selected photoelectron spectra
and photoelectron circular dichroism (PECD) have been recorded by velocity map
imaging, recorded in coincidence with ions, at a number of fixed photon energies.
Translation temperatures of the cluster ions have been further examined by ion
imaging measurements. As well as the sequence of protonated clusters with
integral numbers of butanediol monomer units, a second series with half-integral
monomer masses is observed and deduced to result from a facile cleavage of a
butanediol monomer moiety within the nascent cluster. This second sequence of
half-integral masses displays quite distinct behaviours. PECD measurements are
used to show that the half-integral mass cluster ions do not share a common
parentage with whole integer masses. Using an analogy developed with simple
theoretical calculations of butanediol dimer structures, it is inferred that the
dissociative branching into integral and half-integral ion mass sequences is
controlled by the presence of different butanediol monomer conformations within
the hydrogen bonded clusters.
PMID- 28688423
TI - Photoelectron spectroscopy of the thiazate (NSO-) and thionitrite (SNO-) isomer
anions.
AB - Anion photoelectron spectra of the thiazate (NSO-) and thionitrite (SNO-) isomers
are reported. The NSO- photoelectron spectrum showed several well-resolved
vibronic transitions from the anion to the NSO radical neutral. The electron
affinity of NSO was determined to be 3.113(1) eV. The fundamental vibrational
frequencies of NSO were measured and unambiguously assigned to be 1202(6) cm-1
(nu1, asymmetric stretch), 1010(10) cm-1 (nu2, symmetric stretch), and 300(7) cm
1 (nu3, bend). From the presence of vibrational hot band transitions, the
fundamental vibrational frequencies of the NSO- anion were also measured:
1280(30) cm-1 (nu1, asymmetric stretch), 990(20) cm-1 (nu2, symmetric stretch),
and 480(10) cm-1 (nu3, bend). Combined with the previously measured DeltaacidH298
Ko(HNSO), D0(H-NSO) was found to be 102(5) kcal/mol. Unlike the results from NSO
, the SNO- photoelectron spectrum was broad with little structure, indicative of
a large geometry change between the anion and neutral radical. In addition to the
spectrally congested spectrum, there was evidence of a competition between
photodetachment from SNO- and SNO- photodissociation to form S- + NO. Quantum
chemical calculations were used to aid in the interpretation of the experimental
data and agree well with the observed photoelectron spectra, particularly for the
NSO- isomer.
PMID- 28688424
TI - Universal interrelation between measures of particle and polymer size.
AB - The characterization of many objects involves the determination of a basic set of
particle size measures derived mainly from scattering and transport property
measurements. For polymers, these basic properties include the radius of gyration
Rg, hydrodynamic radius Rh, intrinsic viscosity [eta], and sedimentation
coefficient S, and for conductive particles, the electric polarizability tensor
alphaE and self-capacity C. It is often found that hydrodynamic measurements of
size deviate from each other and from geometric estimates of particle size when
the particle or polymer shape is complex, a phenomenon that greatly complicates
both nanoparticle and polymer characterizations. The present work explores a
general quantitative relation between alphaE, C, and Rg for nanoparticles and
polymers of general shape and the corresponding properties eta, Rh, and Rg using
a hydrodynamic-electrostatic property interrelation.
PMID- 28688425
TI - Real-time observation of multi-mode vibronic coherence in pentafluoropyridine.
AB - The ultrafast dynamics of pentafluoropyridine in the 1 1B2 (pipi*) electronic
state excited at lambdapump = 255 nm is investigated by femtosecond time-resolved
time-of-flight mass spectrometry and photoelectron imaging spectroscopy. A
pronounced, long-lived, and complex periodic modulation of the transient ion
yield signal with contributions by four distinct frequency components, 72 cm-1,
144 cm-1, 251 cm-1, and 281 cm-1, is observed for up to 9 ps. The recorded
photoelectron images display a spectral band from the excited 1 1B2 (pipi*) state
only in the oscillation maxima; the signal is strongly reduced in the oscillation
minima. Supported by electronic structure calculations at the RI-SCS-CC2 and
XMCQDPT2 levels of theory, the oscillating components of the signal are
identified as frequencies of b1 symmetry coupling modes in a vibronic coherence
of the 1 1B2 (pipi*) and 1 1A2 (pisigma*) electronic states. The optical
excitation initiates regular and periodic wavepacket motion along those out-of
plane modes. In the distorted molecular structure, the initially excited state
acquires substantial pisigma* character that modulates the transition dipole
moment for ionization and results in the observed oscillations.
PMID- 28688426
TI - Changing role of carrier gas in formation of ethanol clusters by adiabatic
expansion.
AB - Adiabatic expansion of molecular vapors is a celebrated method for producing pure
and mixed clusters of relevance in both applied and fundamental studies. The
present understanding of the relationship between experimental conditions and the
structure of the clusters formed is incomplete. We explore the role of the
backing/carrier gas during adiabatic expansion of ethanol vapors with regard to
cluster production and composition. Single-component clusters of ethanol were
produced over a wide size-range by varying the rare gas (He, Ar) backing
pressure, with Ar being more efficient than He in promoting the formation of pure
ethanol clusters. However, at stagnation pressures Ps>1.34(4) bar and temperature
49(2) degrees C, synchrotron-based valence and inner-shell photoelectron
spectroscopy reveals condensation of Ar carrier gas on the clusters. Theoretical
calculations of cluster geometries as well as chemical shifts in carbon 1s
ionization energies confirm that the experimental observations are consistent
with an ethanol core covered by an outer shell of argon. Experiments on the 1
propanol/Ar system display a similar pattern as described for ethanol/Ar,
indicating a broader range of validity of the results.
PMID- 28688427
TI - Adsorption of finite semiflexible polymers and their loop and tail distributions.
AB - We discuss the adsorption of semiflexible polymers to a planar attractive wall
and focus on the questions of the adsorption threshold for polymers of finite
length and their loop and tail distributions using both Monte Carlo simulations
and analytical arguments. For the adsorption threshold, we find three regimes:
(i) a flexible or Gaussian regime if the persistence length is smaller than the
adsorption potential range, (ii) a semiflexible regime if the persistence length
is larger than the potential range, and (iii) for finite polymers, a novel
crossover to a rigid rod regime if the deflection length exceeds the contour
length. In the flexible and semiflexible regimes, finite size corrections arise
because the correlation length exceeds the contour length. In the rigid rod
regime, however, it is essential how the global orientational or translational
degrees of freedom are restricted by grafting or confinement. We discuss finite
size corrections for polymers grafted to the adsorbing surface and for polymers
confined by a second (parallel) hard wall. Based on these results, we obtain a
method to analyze adsorption data for finite semiflexible polymers such as
filamentous actin. For the loop and tail distributions, we find power laws with
an exponential decay on length scales exceeding the correlation length. We derive
and confirm the loop and tail power law exponents for flexible and semiflexible
polymers. This allows us to explain that, close to the transition, semiflexible
polymers have significantly smaller loops and both flexible and semiflexible
polymers desorb by expanding their tail length. The tail distribution allows us
to extract the free energy per length of adsorption for actin filaments from
experimental data [D. Welch et al., Soft Matter 11, 7507 (2015)].
PMID- 28688428
TI - Time-resolved multi-mass ion imaging: Femtosecond UV-VUV pump-probe spectroscopy
with the PImMS camera.
AB - The Pixel-Imaging Mass Spectrometry (PImMS) camera allows for 3D charged particle
imaging measurements, in which the particle time-of-flight is recorded along with
(x, y) position. Coupling the PImMS camera to an ultrafast pump-probe velocity
map imaging spectroscopy apparatus therefore provides a route to time-resolved
multi-mass ion imaging, with both high count rates and large dynamic range, thus
allowing for rapid measurements of complex photofragmentation dynamics.
Furthermore, the use of vacuum ultraviolet wavelengths for the probe pulse allows
for an enhanced observation window for the study of excited state molecular
dynamics in small polyatomic molecules having relatively high ionization
potentials. Herein, preliminary time-resolved multi-mass imaging results from
C2F3I photolysis are presented. The experiments utilized femtosecond VUV and UV
(160.8 nm and 267 nm) pump and probe laser pulses in order to demonstrate and
explore this new time-resolved experimental ion imaging configuration. The data
indicate the depth and power of this measurement modality, with a range of
photofragments readily observed, and many indications of complex underlying
wavepacket dynamics on the excited state(s) prepared.
PMID- 28688429
TI - Comment on "Development of an interatomic potential for the simulation of
defects, plasticity, and phase transformations in titanium" [J. Chem. Phys. 145,
154102 (2016)].
PMID- 28688430
TI - Imaging of rotational wave-function in photodissociation of rovibrationally
excited HCl molecules.
AB - We demonstrate a visualization of quantum mechanical phenomena with the velocity
map imaging (VMI) technique, combining vibrationally mediated photodissociation
(VMP) of a simple diatomic HCl with the VMI of its H-photofragments. Free HCl
molecules were excited by a pump infrared (IR) laser pulse to particular
rotational J levels of the v = 2 vibrational state, and subsequently a probe
ultraviolet laser photodissociated the molecule at a fixed wavelength of 243.07
nm where also the H-fragments were ionized. The molecule was aligned by the IR
excitation with respect to the IR laser polarization, and this alignment was
reflected in the angular distribution of the H-photofragments. In particular, the
highest degree of molecular alignment was achieved for the J=1<-0 transition,
which exclusively led to the population of a single rotational state with M = 0.
The obtained images were analyzed for further details of the VMP dynamics, and
different J states were studied as well. Additionally, we investigated the
dynamic evolution of the excited states by changing the pump-probe laser pulse
delay; the corresponding images reflected dephasing due to a coupling between the
molecular angular momentum and nuclear spin. Our measurements confirmed previous
observation using the time-of-flight technique by Sofikitis et al. [J. Chem.
Phys. 127, 144307 (2007)]. We observed a partial recovery of the originally
excited state after 60 ns in agreement with the previous observation.
PMID- 28688431
TI - Dynamics of supercooled liquid and plastic crystalline ethanol: Dielectric
relaxation and AC nanocalorimetry distinguish structural alpha- and Debye
relaxation processes.
AB - Physical vapor deposition has been used to prepare glasses of ethanol. Upon
heating, the glasses transformed into the supercooled liquid phase and then
crystallized into the plastic crystal phase. The dynamic glass transition of the
supercooled liquid is successfully measured by AC nanocalorimetry, and
preliminary results for the plastic crystal are obtained. The frequency
dependences of these dynamic glass transitions observed by AC nanocalorimetry are
in disagreement with conclusions from previously published dielectric spectra of
ethanol. Existing dielectric loss spectra have been carefully re-evaluated
considering a Debye peak, which is a typical feature in the dielectric loss
spectra of monohydroxy alcohols. The re-evaluated dielectric fits reveal a
prominent dielectric Debye peak, a smaller and asymmetrically broadened peak,
which is identified as the signature of the structural alpha-relaxation and a
Johari-Goldstein secondary relaxation process. This new assignment of the
dielectric processes is supported by the observation that the AC nanocalorimetry
dynamic glass transition temperature, Talpha, coincides with the dielectric
structural alpha-relaxation process rather than the Debye process. The combined
results from dielectric spectroscopy and AC nanocalorimetry on the plastic
crystal of ethanol suggest the occurrence of a Debye process also in the plastic
crystal phase.
PMID- 28688432
TI - Assessment of elastic models in supercooled water: A molecular dynamics study
with the TIP4P/2005f force field.
AB - Glass formers exhibit a viscoelastic behavior: at the laboratory time scale, they
behave like (glassy) solids at low temperatures and like liquids at high
temperatures. Based on this observation, elastic models relate the long time
supercooled dynamics to short time elastic properties of the supercooled liquid.
In the present work, we assess the validity of elastic models for the shear
viscosity and the alpha-relaxation time of supercooled water, using molecular
dynamics simulations with the TIP4P/2005f force field over a wide range of
temperatures. We show that elastic models provide a good description of
supercooled water dynamics. For the viscosity, two different regimes are observed
and the crossover temperature is found to be close to the one where the Stokes
Einstein relation starts to be violated. Our simulations show that only shear
properties are important to characterize the effective flow activation energy.
This study calls for experimental determination of the high frequency elastic
properties of water at low temperatures.
PMID- 28688433
TI - Imaging state-to-state reactive scattering in the Ar+ + H2 charge transfer
reaction.
AB - The charge transfer reaction of Ar+ with H2 and D2 has been investigated in an
experiment combining crossed beams with three-dimensional velocity map imaging.
Angle-differential cross sections for two collision energies have been obtained
for both neutral species. We find that the product ions are highly internally
excited. In the reaction with H2, the spin-orbit excited Ar+ state's coupling to
the "resonant" vibrationally excited product H2+ (upsilon = 2) dominates for both
investigated energies, in line with previous investigations. The observed angular
distributions, however, show significantly less back-scattering than was found
previously. Furthermore, we discovered that the product ions are highly
rotationally excited. In the case of Ar+ reacting with D2, the energetically
closest lying vibrational levels are not strictly preferred and higher-lying
vibrational levels are also populated. For both species, the backward-scattered
products show higher internal excitation.
PMID- 28688434
TI - Nonadiabatic laser-induced alignment of molecules: Reconstructing ?????????
theta? directly from ????????? theta2D? by Fourier analysis.
AB - We present an efficient, noise-robust method based on Fourier analysis for
reconstructing the three-dimensional measure of the alignment degree,
?cos2theta?, directly from its two-dimensional counterpart, ?cos2theta2D?. The
method applies to nonadiabatic alignment of linear molecules induced by a
linearly polarized, nonresonant laser pulse. Our theoretical analysis shows that
the Fourier transform of the time-dependent ?cos2theta2D? trace over one
molecular rotational period contains additional frequency components compared to
the Fourier transform of ?cos2theta?. These additional frequency components can
be identified and removed from the Fourier spectrum of ?cos2theta2D?. By
rescaling of the remaining frequency components, the Fourier spectrum of
?cos2theta? is obtained and, finally, ?cos2theta? is reconstructed through
inverse Fourier transformation. The method allows the reconstruction of the
?cos2theta? trace from a measured ?cos2theta2D? trace, which is the typical
observable of many experiments, and thereby provides direct comparison to
calculated ?cos2theta? traces, which is the commonly used alignment metric in
theoretical descriptions. We illustrate our method by applying it to the
measurement of nonadiabatic alignment of I2 molecules. In addition, we present an
efficient algorithm for calculating the matrix elements of cos2theta2D and any
other observable in the symmetric top basis. These matrix elements are required
in the rescaling step, and they allow for highly efficient numerical calculation
of ?cos2theta2D? and ?cos2theta? in general.
PMID- 28688436
TI - A method of extracting speed-dependent vector correlations from 2 + 1 REMPI ion
images.
AB - We present analytical expressions for extracting Dixon's bipolar moments in the
semi-classical limit from experimental anisotropy parameters of sliced or
reconstructed non-sliced images. The current method focuses on images generated
by 2 + 1 REMPI (Resonance Enhanced Multi-photon Ionization) and is a necessary
extension of our previously published 1 + 1 REMPI equations. Two approaches for
applying the new equations, direct inversion and forward convolution, are
presented. As demonstration of the new method, bipolar moments were extracted
from images of carbonyl sulfide (OCS) photodissociation at 230 nm and NO2
photodissociation at 355 nm, and the results are consistent with previous
publications.
PMID- 28688437
TI - Ionic size effects on the Poisson-Boltzmann theory.
AB - In this paper, we develop a simple theory to study the effects of ionic size on
ionic distributions around a charged spherical particle. We include a correction
to the regular Poisson-Boltzmann equation in order to take into account the size
of ions in a mean-field regime. The results are compared with Monte Carlo
simulations and a density functional theory based on the fundamental measure
approach and a second-order bulk expansion which accounts for electrostatic
correlations. The agreement is very good even for multivalent ions. Our results
show that the theory can be applied with very good accuracy in the description of
ions with highly effective ionic radii and low concentration, interacting with a
colloid or a nanoparticle in an electrolyte solution.
PMID- 28688435
TI - Influence of long-range Coulomb interaction in velocity map imaging.
AB - The standard velocity-map imaging (VMI) analysis relies on the simple
approximation that the residual Coulomb field experienced by the photoelectron
ejected from a neutral or ion system may be neglected. Under this almost
universal approximation, the photoelectrons follow ballistic (parabolic)
trajectories in the externally applied electric field, and the recorded image may
be considered as a 2D projection of the initial photoelectron velocity
distribution. There are, however, several circumstances where this approximation
is not justified and the influence of long-range forces must absolutely be taken
into account for the interpretation and analysis of the recorded images. The aim
of this paper is to illustrate this influence by discussing two different
situations involving isolated atoms or molecules where the analysis of
experimental images cannot be performed without considering long-range Coulomb
interactions. The first situation occurs when slow (meV) photoelectrons are
photoionized from a neutral system and strongly interact with the attractive
Coulomb potential of the residual ion. The result of this interaction is the
formation of a more complex structure in the image, as well as the appearance of
an intense glory at the center of the image. The second situation, observed also
at low energy, occurs in the photodetachment from a multiply charged anion and it
is characterized by the presence of a long-range repulsive potential. Then, while
the standard VMI approximation is still valid, the very specific features
exhibited by the recorded images can be explained only by taking into
consideration tunnel detachment through the repulsive Coulomb barrier.
PMID- 28688438
TI - Real-time detection of S(1D2) photofragments produced from the 1B2(1Sigmau+)
state of CS2 by vacuum ultraviolet photoelectron imaging using 133 nm probe
pulses.
AB - Ultrafast photodissociation dynamics from the 1B2(1Sigmau+) state of CS2 are
studied by time-resolved photoelectron imaging using the fourth (4omega, 198 nm)
and sixth (6omega, 133 nm) harmonics of a femtosecond Ti:sapphire laser. The 1B2
state of CS2 was prepared with the 4omega pulses, and subsequent dynamics were
probed using the 6omega vacuum ultraviolet (VUV) pulses. The VUV pulses enabled
real-time detection of S(1D2) photofragments, produced via CS2*(1B2(1Sigmau+)) ->
CS(X 1Sigma+) + S(1D2). The photoionization signal of dissociating
CS2*(1B2(1Sigmau+)) molecules starts to decrease at about 100 fs, while the
S(1D2) fragments appear with a finite (ca. 400 fs) delay time after the pump
pulse. Also discussed is the configuration interaction of the 1B2(1Sigmau+) state
based on relative photoionization cross-sections to different cationic states.
PMID- 28688439
TI - Bulk-mediated surface transport in the presence of bias.
AB - Surface transport, when the particle is allowed to leave the surface, travel in
the bulk for some time, and then return to the surface, is referred to as bulk
mediated surface transport. Recently, we proposed a formalism that significantly
simplifies analysis of bulk-mediated surface diffusion [A. M. Berezhkovskii, L.
Dagdug, and S. M. Bezrukov, J. Chem. Phys. 143, 084103 (2015)]. Here this
formalism is extended to bulk-mediated surface transport in the presence of bias,
i.e., when the particle has arbitrary drift velocities on the surface and in the
bulk. A key advantage of our approach is that the transport problem reduces to
that of a two-state problem of the particle transitions between the surface and
the bulk. The latter can be solved with relative ease. The formalism is used to
find the Laplace transforms of the first two moments of the particle displacement
over the surface in time t at arbitrary values of the particle drift velocities
and diffusivities on the surface and in the bulk. This allows us to analyze in
detail the time dependence of the effective drift velocity of the particle on the
surface, which can be highly nontrivial.
PMID- 28688440
TI - The energy dependence of CO(v,J) produced from H2CO via the transition state,
roaming, and triple fragmentation channels.
AB - The dynamics of CO production from photolysis of H2CO have been explored over a
8000 cm-1 energy range (345 nm-266 nm). Two-dimensional ion imaging, which
simultaneously measures the speed and angular momentum distribution of a
photofragment, was used to characterise the distribution of rotational and
translational energy and to quantify the branching fraction of roaming,
transition state (TS), and triple fragmentation (3F) pathways. The rotational
distribution for the TS channel broadens significantly with increasing energy,
while the distribution is relatively constant for the roaming channel. The
branching fraction from roaming is also relatively constant at 20% of the
observed CO. Above the 3F threshold, roaming decreases in favour of triple
fragmentation. Combining the present data with our previous study on the H-atom
branching fractions and published quantum yields for radical and molecular
channels, absolute quantum yields were determined for all five dissociation
channels for the entire S1<-S0 absorption band, covering almost 8000 cm-1 of
excitation energy. The S0 radical and TS molecular channels are the most
important over this energy range. The absolute quantum yield of roaming is fairly
constant ~5% at all energies. The T1 radical channel is important (20%-40%)
between 1500 and 4000 cm-1 above the H + HCO threshold, but becomes unimportant
at higher energy. Triple fragmentation increases rapidly above its threshold
reaching a maximum of 5% of the total product yield at the highest energy.
PMID- 28688441
TI - Nanoscale investigations on interchain organization in thin films of polymer
liquid crystal blend.
AB - Optimized nanomorphology in organic thin active layers is crucial for good
performance in organic solar cells. However, the relation between morphology and
electronic properties at nanoscale remains not completely understood. Here, we
study the effect of film thickness and temperature annealing on the ordering of
poly(3-hexylthiophene) chains when the polymer is blended with a columnar liquid
crystalline molecule. Electronic absorption, atomic force microscopy
measurements, and Raman spectroscopy show that morphology and chain ordering of
the blend depend on the film thickness. We highlight the benefit of using a
liquid crystal in organic blends, opening the way to use simple processing
methods for the fabrication of organic electronic devices.
PMID- 28688443
TI - Coincidence velocity map imaging using a single detector.
AB - We demonstrate a single-detector velocity map imaging setup which is capable of
rapidly switching between coincidence and non-coincidence measurements. By
rapidly switching the extraction voltages on the electrostatic lenses, both
electrons and ions can be collected in coincidence with a single detector. Using
a fast camera as the 2D detector avoids the saturation problem associated with
traditional delay line detectors and allows for easy transitions between
coincidence and non-coincidence data collection modes. This is a major advantage
in setting up a low-cost and versatile coincidence apparatus. We present both
coincidence and non-coincidence measurements of strong field atomic and molecular
ionization.
PMID- 28688442
TI - Perspective: Advanced particle imaging.
AB - Since the first ion imaging experiment [D. W. Chandler and P. L. Houston, J.
Chem. Phys. 87, 1445-1447 (1987)], demonstrating the capability of collecting an
image of the photofragments from a unimolecular dissociation event and analyzing
that image to obtain the three-dimensional velocity distribution of the
fragments, the efficacy and breadth of application of the ion imaging technique
have continued to improve and grow. With the addition of velocity mapping,
ion/electron centroiding, and slice imaging techniques, the versatility and
velocity resolution have been unmatched. Recent improvements in molecular beam,
laser, sensor, and computer technology are allowing even more advanced particle
imaging experiments, and eventually we can expect multi-mass imaging with co
variance and full coincidence capability on a single shot basis with repetition
rates in the kilohertz range. This progress should further enable "complete"
experiments-the holy grail of molecular dynamics-where all quantum numbers of
reactants and products of a bimolecular scattering event are fully determined and
even under our control.
PMID- 28688444
TI - Ab initio lifetime correction to scattering states for time-dependent electronic
structure calculations with incomplete basis sets.
AB - We propose a method for obtaining effective lifetimes of scattering electronic
states for avoiding the artificial confinement of the wave function due to the
use of incomplete basis sets in time-dependent electronic-structure calculations
of atoms and molecules. In this method, using a fitting procedure, the lifetimes
are extracted from the spatial asymptotic decay of the approximate scattering
wave functions obtained with a given basis set. The method is based on a rigorous
analysis of the complex-energy solutions of the Schrodinger equation. It gives
lifetimes adapted to any given basis set without using any empirical parameters.
The method can be considered as an ab initio version of the heuristic lifetime
model of Klinkusch et al. [J. Chem. Phys. 131, 114304 (2009)]. The method is
validated on H and He atoms using Gaussian-type basis sets for the calculation of
high-harmonic-generation spectra.
PMID- 28688445
TI - Imaging characterization of the rapid adiabatic passage in a source-rotatable,
crossed-beam scattering experiment.
AB - In order to achieve a more efficient preparation of a specific ro-vibrationally
excited reactant state for reactive scattering experiments, we implemented the
rapid adiabatic passage (RAP) scheme to our pulsed crossed-beam machine, using a
single-mode, continuous-wave mid-infrared laser. The challenge for this source
rotatable apparatus lies in the non-orthogonal geometry between the molecular
beam and the laser propagation directions. As such, the velocity spread of the
supersonic beam results in a significantly broader Doppler distribution that
needs to be activated for RAP to occur than the conventional orthogonal
configuration. In this report, we detail our approach to shifting, locking, and
stabilizing the absolute mid-infrared frequency. We exploited the imaging
detection technique to characterize the RAP process and to quantify the
excitation efficiency. We showed that with appropriate focusing of the IR laser,
a nearly complete population transfer can still be achieved in favorable cases.
Compared to our previous setup-a pulsed optical parametric oscillator/amplifier
in combination with a multipass ring reflector for saturated absorption, the
present RAP scheme with a single-pass, continuous-wave laser yields noticeably
higher population-transfer efficiency.
PMID- 28688446
TI - Slow photoelectron velocity-map imaging of cold tert-butyl peroxide.
AB - Photoelectron spectra of cryogenically cooled X~1A' tert-butyl peroxide anions
are obtained using slow electron velocity-map imaging. The spectra show highly
structured bands corresponding to detachment to the X~2A" and A~2A' electronic
states of the neutral radical and represent a notable improvement in resolution
over previous photoelectron spectra. We report an electron affinity of 1.1962(20)
eV and a term energy T0(A~2A') of 0.9602(24) eV for the tert-butyl peroxy
radical. New vibrational structure is resolved, providing several frequencies for
both neutral states. Additionally, the threshold behavior of the photodetachment
cross section is investigated within the context of Dyson orbital calculations.
PMID- 28688447
TI - Electron affinity and excited states of methylglyoxal.
AB - Using photoelectron imaging spectroscopy, we characterized the anion of
methylglyoxal (X2A" electronic state) and three lowest electronic states of the
neutral methylglyoxal molecule: the closed-shell singlet ground state (X1A'), the
lowest triplet state (a3A"), and the open-shell singlet state (A1A"). The
adiabatic electron affinity (EA) of the ground state, EA(X1A') = 0.87(1) eV,
spectroscopically determined for the first time, compares to 1.10(2) eV for
unsubstituted glyoxal. The EAs (adiabatic attachment energies) of two excited
states of methylglyoxal were also determined: EA(a3A") = 3.27(2) eV and EA(A1A")
= 3.614(9) eV. The photodetachment of the anion to each of these two states
produces the neutral species near the respective structural equilibria; hence,
the a3A" <- X2A" and A1A" <- X2A" photodetachment transitions are dominated by
intense peaks at their respective origins. The lowest-energy photodetachment
transition, on the other hand, involves significant geometry relaxation in the
X1A' state, which corresponds to a 60 degrees internal rotation of the methyl
group, compared to the anion structure. Accordingly, the X1A' <- X2A" transition
is characterized as a broad, congested band, whose vertical detachment energy,
VDE = 1.20(4) eV, significantly exceeds the adiabatic EA. The experimental
results are in excellent agreement with the ab initio predictions using several
equation-of-motion methodologies, combined with coupled-cluster theory.
PMID- 28688448
TI - Valence shell threshold photoelectron spectroscopy of the CHxCN (x = 0-2) and CNC
radicals.
AB - We present the photoelectron spectroscopy of four radical species, CHxCN (x = 0
2) and CNC, formed in a microwave discharge flow-tube reactor by consecutive H
abstractions from CH3CN (CHxCN + F -> CHx-1CN + HF (x = 1-3)). The spectra were
obtained combining tunable vacuum ultraviolet synchrotron radiation with double
imaging electron/ion coincidence techniques, which yielded mass-selected
threshold photoelectron spectra. The results obtained for H2CCN complement
existing ones while for the other radicals the data represent the first
observation of their (single-photon) ionizing transitions. In the case of H2CCN,
Franck-Condon calculations have been performed in order to assign the vibrational
structure of the X+ 1A1<-X 2B1 ionizing transition. A similar treatment for the
HCCN, CCN, and CNC radicals appeared to be more complicated mainly because a
Renner-Teller effect strongly affects the vibrational levels of the ground
electronic state of the HCCN+, CCN, and CNC species. Nevertheless, the first
adiabatic ionization energies of these radicals are reported and compared to our
ab initio calculated values, leading to new values for enthalpies of formation
(DeltafH2980(HCCN+(X2A'))=1517+/-12kJmol-1,DeltafH2980(CCN(X2Pi))=682+/-13kJmol
1, and DeltafH2980(CNC(X2Pig))=676+/-12kJmol-1), which are of fundamental
importance for astrochemistry.
PMID- 28688449
TI - Efficient chemical potential evaluation with kinetic Monte Carlo method and non
uniform external potential: Lennard-Jones fluid, liquid, and solid.
AB - The aim of this paper is to present a method of a direct evaluation of the
chemical potential of fluid, liquid, and solid with kinetic Monte Carlo
simulation. The method is illustrated with the 12-6 Lennard-Jones (LJ) system
over a wide range of density and temperature. A distinctive feature of the
methodology used in the present study is imposing an external potential on the
elongated simulation box to split the system into two equilibrium phases, one of
which is substantially diluted. This technique provides a reliable direct
evaluation of the chemical potential of the whole non-uniform system (including
that of the uniformly distributed dense phase in the central zone of the box),
which, for example, is impossible in simulation of the uniform crystalline phase.
The parameters of the vapor-liquid, liquid-solid, and fluid-solid transitions
have been reliably determined. The chemical potential and the pressure are
defined as thermodynamically consistent functions of density and temperature
separately for the liquid and the solid (FCC) phases. It has been shown that in
two-phase systems separated by a flat interface, the crystal melting always
occurs at equilibrium conditions. It is also proved that in the limit of zero
temperature, the specific heat capacity of an LJ crystal at constant volume is
exactly 3Rg (where Rg is the gas constant) without resorting to harmonic
oscillators.
PMID- 28688450
TI - Alignment, orientation, and Coulomb explosion of difluoroiodobenzene studied with
the pixel imaging mass spectrometry (PImMS) camera.
AB - Laser-induced adiabatic alignment and mixed-field orientation of 2,6
difluoroiodobenzene (C6H3F2I) molecules are probed by Coulomb explosion imaging
following either near-infrared strong-field ionization or extreme-ultraviolet
multi-photon inner-shell ionization using free-electron laser pulses. The
resulting photoelectrons and fragment ions are captured by a double-sided
velocity map imaging spectrometer and projected onto two position-sensitive
detectors. The ion side of the spectrometer is equipped with a pixel imaging mass
spectrometry camera, a time-stamping pixelated detector that can record the hit
positions and arrival times of up to four ions per pixel per acquisition cycle.
Thus, the time-of-flight trace and ion momentum distributions for all fragments
can be recorded simultaneously. We show that we can obtain a high degree of one
and three-dimensional alignment and mixed-field orientation and compare the
Coulomb explosion process induced at both wavelengths.
PMID- 28688451
TI - Alignment of the hydrogen molecule under intense laser fields.
AB - Alignment of the electronically excited E,F state of the H2 molecule is studied
using the velocity mapping imaging technique. Photofragment images of H+ due to
the dissociation mechanism that follows the 2-photon excitation into the (E,F; nu
= 0, J = 0) electronic state show a strong dependence on laser intensity, which
is attributed to the high polarizability anisotropy of the H2 (E,F) state. We
observe a marked structure in the angular distribution, which we explain as the
interference between the prepared J = 0 and Stark-mixed J = 2 rovibrational
states of H2, as the laser intensity increases. Quantification of these effects
allows us to extract the polarizability anisotropy of the H2 (E,F J = 0) state
yielding a value of 312 +/- 82 a.u. (46 A3). By comparison, CS2 has 10 A3, I2 has
7 A3, and hydrochlorothiazide (C7H8ClN3O4S2) has about 25 A3 meaning that we have
created the most easily aligned molecule ever measured, by creating a mixed
superposition state that is highly anisotropic in its polarizability.
PMID- 28688453
TI - Mycoplasma pneumoniae as a cause of vulvar ulcers in a non-sexually active girl:
a case report.
AB - BACKGROUND: Non-sexually active young females very rarely develop genital ulcers.
Such ulcers pose a diagnostic challenge as well as physical and emotional
distress for patients and family; therefore, the search for their etiology
requires exhaustive investigation. Several viruses such as Epstein-Barr virus
have been associated with this entity; however, Mycoplasma pneumoniae has rarely
been linked to such ulcers in the literature. We present a case of vulvar ulcers
in a non-sexually active young girl during the course of pneumonia caused by
Mycoplasma pneumoniae. CASE PRESENTATION: A 10-year-old non-sexually active girl
of cypriot origin presented at a hospital with fever, dry cough, and acute vulvar
ulcers. Laboratory investigations as well as imaging studies revealed Mycoplasma
pneumoniae as the cause of her pneumonia and acute vulvar ulcers. CONCLUSIONS:
Although a rare cause of vulvar ulcers, Mycoplasma pneumoniae should be
considered in the differential diagnosis of acute vulvar ulcers coexisting with
respiratory symptoms.
PMID- 28688454
TI - Reassortment process after co-infection of pigs with avian H1N1 and swine H3N2
influenza viruses.
AB - BACKGROUND: The influenza A virus is highly variable, which, to some degree, is
caused by the reassortment of viral genetic material. This process plays a major
role in the generation of novel influenza virus strains that can emerge in a new
host population. Due to the susceptibility of pigs to infections with avian,
swine and human influenza viruses, they are considered intermediate hosts for the
adaptation of the avian influenza virus to humans. In order to test the
reassortment process in pigs, they were co-infected with H3N2
A/swine/Gent/172/2008 (Gent/08) and H1N1 A/duck/Italy/1447/2005 (Italy/05) and co
housed with a group of naive piglets. RESULTS: The Gent/08 strains dominated over
Italy/05, but reassortment occurred. The reassortant strains of the H1N1 subtype
(12.5%) with one gene (NP or M) of swine-origin were identified in the nasal
discharge of the contact-exposed piglets. CONCLUSIONS: These results demonstrate
that despite their low efficiency, genotypically and phenotypically different
influenza A viruses can undergo genetic exchange during co-infection of pigs.
PMID- 28688455
TI - Foot use during vertical climbing in chimpanzees (Pan troglodytes).
AB - Upright bipedalism is a hallmark of hominin locomotion, however debates continue
regarding the extent of arboreal locomotion and the nature of bipedalism
practiced by early hominins. Pedal form and function play a prominent role in
these debates, as the foot is the element that directly interacts with the
locomotor substrate. Recent finds have substantially increased the availability
of associated foot remains of early hominins and emphasized the enigmatic nature
of the early evolution of human bipedalism. New discoveries of associated
forefoot remains have afforded the opportunity to assess relative proportions
across the forefoot of fossil hominins and illuminated the need for data on
relative loading across the forefoot in extant hominoids. In order to provide
functional data with which to examine the relationship between bony features and
load distribution across the forefoot during climbing, we present the first
analysis of plantar pressure distribution across the forefoot of chimpanzees
climbing a vertical support. Chimpanzees load the medial metatarsals and first
toe disproportionately during vertical climbing. Peak pressures on these elements
occur at the end of stance phase during climbing and are higher than on any other
elements of the foot. Toe pressures are considerably higher during vertical
climbing than during knuckle-walking or movement on horizontal poles, supporting
the notion that the plantarly-broad and dorsally-narrow metatarsal heads in
chimpanzees and some early hominins are associated with close-packing of the
metatarsophalangeal joint during climbing.
PMID- 28688456
TI - The social organization of Homo ergaster: Inferences from anti-predator responses
in extant primates.
AB - Patterns of primate socioecology have been used to suggest that the first truly
savanna-dwelling hominin, Homo ergaster, lived in sizeable groups. Here, we
revisit these estimates and infer additional features of the social organization
of these early hominins based on anti-predator responses observed across the
primate taxon. We first show that the effect of habitat on primate group size,
composition, and sexual dimorphism is negligible after controlling for substrate
use and phylogeny: terrestrial species live in larger groups with more and bigger
males than arboreal taxa. We next hypothesize that groups can only survive in
open habitats if males are able to engage in joint counter-attacks against the
large carnivorans typical of such environments. To test this, we analyze reports
on primate counter-attacks against known predators and find these are indeed
disproportionately frequent in terrestrial taxa living in open habitats,
sometimes even involving the use of tentative weapons. If we subsequently only
examine the taxa that are particularly adept at this (chimpanzees and baboons),
we find an effect of habitat type on group size: groups on the savanna are larger
than those in the forest. We thus infer that H. ergaster lived in very large
groups with many males that jointly defended the group against carnivorans, and
argue that these counter-attacks will readily have turned into confrontational
scavenging and cooperative hunting, allowing Homo to move into the niche of
social carnivore. These two features (life in very large multi-male groups and a
switch to persistent carnivory) shaped the evolution of our lineage to such an
extent that the social organization of H. ergaster may already have contained
many key elements characterizing modern day foragers: male bonding, incipient
male-female friendships with food sharing, a tendency toward endogamy, and the
presence of large communities that eventually turned into the ethno-linguistic
units we can still recognize today.
PMID- 28688457
TI - U-series dating and classification of the Apidima 2 hominin from Mani Peninsula,
Southern Greece.
AB - Laser ablation U-series dating results on a human cranial bone fragment from
Apidima, on the western cost of the Mani Peninsula, Southern Greece, indicate a
minimum age of 160,000 years. The dated cranial fragment belongs to Apidima 2,
which preserves the facial skeleton and a large part of the braincase, lacking
the occipital bone. The morphology of the preserved regions of the cranium, and
especially that of the facial skeleton, indicates that the fossil belongs to the
Neanderthal clade. The dating of the fossil at a minimum age of 160,000 years
shows that most of the Neanderthal traits were already present in the MIS 6 and
perhaps earlier. This makes Apidima 2 the earliest known fossil with a clear
Neanderthal facial morphology. Together with the nearby younger Neanderthal
specimens from Lakonis and Kalamakia, the Apidima crania are of crucial
importance for the evolution of Neanderthals in the area during the Middle to
Late Pleistocene. It can be expected that systematic direct dating of the other
human fossils from this area will elucidate our understanding of Neanderthal
evolution and demise.
PMID- 28688452
TI - Crossroads between peripheral atherosclerosis, western-type diet and skeletal
muscle pathophysiology: emphasis on apolipoprotein E deficiency and peripheral
arterial disease.
AB - Atherosclerosis is a chronic inflammatory process that, in the presence of
hyperlipidaemia, promotes the formation of atheromatous plaques in large vessels
of the cardiovascular system. It also affects peripheral arteries with major
implications for a number of other non-vascular tissues such as the skeletal
muscle, the liver and the kidney. The aim of this review is to critically discuss
and assimilate current knowledge on the impact of peripheral atherosclerosis and
its implications on skeletal muscle homeostasis. Accumulating data suggests that
manifestations of peripheral atherosclerosis in skeletal muscle originates in a
combination of increased i)-oxidative stress, ii)-inflammation, iii)
mitochondrial deficits, iv)-altered myofibre morphology and fibrosis, v)-chronic
ischemia followed by impaired oxygen supply, vi)-reduced capillary density, vii)-
proteolysis and viii)-apoptosis. These structural, biochemical and
pathophysiological alterations impact on skeletal muscle metabolic and
physiologic homeostasis and its capacity to generate force, which further affects
the individual's quality of life. Particular emphasis is given on two major areas
representing basic and applied science respectively: a)-the abundant evidence
from a well-recognised atherogenic model; the Apolipoprotein E deficient mouse
and the role of a western-type diet and b)-on skeletal myopathy and oxidative
stress-induced myofibre damage from human studies on peripheral arterial disease.
A significant source of reactive oxygen species production and oxidative stress
in cardiovascular disease is the family of NADPH oxidases that contribute to
several pathologies. Finally, strategies targeting NADPH oxidases in skeletal
muscle in an attempt to attenuate cellular oxidative stress are highlighted,
providing a better understanding of the crossroads between peripheral
atherosclerosis and skeletal muscle pathophysiology.
PMID- 28688458
TI - Dating the Middle Paleolithic deposits of La Quina Amont (Charente, France) using
luminescence methods.
AB - The site of La Quina Amont, located in the Charente region, is one of the most
important sites in southwestern France for studying major changes in human
behaviors from the Middle Paleolithic (MP) to the Early Upper Paleolithic (EUP).
Extensively excavated over the past 50 years, numerous dating studies have been
focused on the Upper Paleolithic deposits using radiocarbon on bone collagen and
thermoluminescence (TL) on heated flints; however, the Mousterian levels remain
undated due to the scarcity of suitable materials. Our investigations aimed to
provide for the first time a chronological framework for the site using
luminescence dating methods on different minerals contained in the sediments.
Coarse grains of quartz were dated using the optically stimulated luminescence
(OSL) technique, and polymineral fine grains were dated using both infrared
(IRSL) and post-infrared (pIR-IRSL) stimulated luminescence signals. OSL, IRSL
and pIR-IRSL results were combined with available TL and radiocarbon data sets to
propose a chronology for the site. The agreement between these methods provides
key insights into the sedimentological processes involved in the site formation
and into the chronology of the human occupations. In particular, it shows that
the sequence spans almost ~20,000 years (20 ka). Moreover, the new chronological
framework suggests that the makers of the Quina lithic technocomplex (LTC), who
were reindeer hunters, inhabited the site from the end of marine isotope stage
(MIS) 4 to the beginning of MIS 3. We also show that Levallois and Discoidal
industries occurred successively under temperate paleoclimatic conditions, during
MIS 3 but not after ~40 ka. Finally, we compare the Quina LTC dataset with other
sites in southern France in order to shed light upon the variability in
Mousterian industries of this region.
PMID- 28688459
TI - New cranium of the large cercopithecid primate Theropithecus oswaldi leakeyi
(Hopwood, 1934) from the paleoanthropological site of Makuyuni, Tanzania.
AB - The Pleistocene hominin site of Makuyuni, near Lake Manyara, Tanzania, is known
for fossils attributable to Homo and Acheulean artifacts (Ring et al., 2005;
Kaiser et al., 2010; Frost et al., 2012). Here we describe the fossil primate
material from the Manyara Beds, which includes the first nearly complete female
cranium of Theropithecus oswaldi leakeyi and a proximal tibia from the same
taxon. The cranium is dated to between 633 and 780 Ka and the tibia to the
Pleistocene. The T. oswaldi lineage is one of the most important among Neogene
mammals of Africa: it is both widespread and abundant. The size of the dentition,
cranium, and tibia all confirm the previously recognized trend of increasing body
size in this lineage and make their taxonomic assignments secure. The morphology
of this specimen provides new insights into the evolution of this lineage through
time, as well as its geographic variation and sexual dimorphism. The cranium also
shows damage consistent with a mammalian carnivore, most likely a felid. The
identification of this material as representing T. o. leakeyi agrees with the
Middle Pleistocene age estimates for the MK4 locality in particular and the
Manyara Beds in general.
PMID- 28688460
TI - Chronometric investigations of the Middle to Upper Paleolithic transition in the
Zagros Mountains using AMS radiocarbon dating and Bayesian age modelling.
AB - The Middle to Upper Paleolithic transition is often linked with a bio-cultural
shift involving the dispersal of modern humans outside of Africa, the concomitant
replacement of Neanderthals across Eurasia, and the emergence of new
technological traditions. The Zagros Mountains region assumes importance in
discussions concerning this period as its geographic location is central to all
pertinent hominin migration areas, pointing to both east and west. As such,
establishing a reliable chronology in the Zagros Mountains is crucial to our
understanding of these biological and cultural developments. Political
circumstance, coupled with the poor preservation of organic material, has meant
that a clear chronological definition of the Middle to Upper Paleolithic
transition for the Zagros Mountains region has not yet been achieved. To improve
this situation, we have obtained new archaeological samples for AMS radiocarbon
dating from three sites: Kobeh Cave, Kaldar Cave, and Ghar-e Boof (Iran). In
addition, we have statistically modelled previously published radiocarbon
determinations for Yafteh Cave (Iran) and Shanidar Cave (Iraqi Kurdistan), to
improve their chronological resolution and enable us to compare the results with
the new dataset. Bayesian modelling results suggest that the onset of the Upper
Paleolithic in the Zagros Mountains dates to 45,000-40,250 cal BP (68.2%
probability). Further chronometric data are required to improve the precision of
this age range.
PMID- 28688461
TI - Further human fossils from the Middle Stone Age deposits of Die Kelders Cave 1,
Western Cape Province, South Africa.
PMID- 28688462
TI - Editorial overview: Developmental mechanisms, patterning and evolution:
Developmental patterning: from stochasticity to plasticity.
PMID- 28688463
TI - Affirming the Mission of Mayo Clinic Proceedings.
PMID- 28688464
TI - Parkinson Disease and Melanoma: Confirming and Reexamining an Association.
AB - OBJECTIVE: To examine an association between melanoma and Parkinson disease (PD).
PATIENTS AND METHODS: Phase I: Rochester Epidemiology Project records were used
to identify (between January 1, 1976, and December 31, 2013) patients with PD in
Olmsted County, Minnesota, with 3 matched controls per case. After review, JMP
statistical software with logistic regression analysis was used to assess the
risk of preexisting melanoma in patients with PD vs controls. Phase II: All
Rochester Epidemiology Project cases of melanoma were identified (between January
1, 1976, and December 31, 2014), with 1 control per case. A Cox proportional
hazards model was used to assess the risk of developing PD after the index date
in cases vs controls, and Kaplan-Meier analysis was performed to determine the 35
year cumulative risk of PD. A Cox proportional hazards model was used to assess
the risk of death from metastatic melanoma in patients with melanoma without PD
compared with those with PD. RESULTS: Phase I: Patients with PD had a 3.8-fold
increased likelihood of having preexisting melanoma as compared with controls
(95% CI, 2.1-6.8; P<.001). Phase II: Patients with melanoma had a 4.2-fold
increased risk of developing PD (95% CI, 2.0-8.8; P<.001). Kaplan-Meier analysis
revealed an increased 35-year cumulative risk of PD in patients with melanoma
(11.8%) compared with controls (2.6%) (P<.001). Patients with melanoma without PD
had a 10.5-fold increased relative risk of death from metastatic melanoma
compared with patients with melanoma with PD (95% CI, 1.5-72.2) (P=.02).
CONCLUSION: There appears to be an association between melanoma and PD. Further
study is warranted; but on the basis of these results, physicians may consider
counseling patients with melanoma about PD risk and implementing cutaneous and
ocular melanoma surveillance in patients with PD.
PMID- 28688465
TI - Chronic Obstructive Pulmonary Disease Phenotypes: Implications for Care.
AB - Chronic obstructive pulmonary disease (COPD) phenotyping can help define clusters
of patients with common characteristics that relate to clinically meaningful
outcomes. In this review, we describe 7 clinically meaningful COPD phenotypes
that can be identified by primary care physicians as well as specialists and that
have specific management and prognostic implications: (1) asthma-COPD overlap
phenotype, (2) frequent exacerbator phenotype, (3) upper lobe-predominant
emphysema phenotype, (4) rapid decliner phenotype, (5) comorbid COPD phenotype,
(6) physical frailty phenotype, and (7) emotional frailty phenotype.
PMID- 28688466
TI - Leukemic Transformation in Myeloproliferative Neoplasms: A Literature Review on
Risk, Characteristics, and Outcome.
AB - Myeloproliferative neoplasms (MPNs) operationally include essential
thrombocythemia, polycythemia vera, primary myelofibrosis (PMF), and prefibrotic
PMF. All 4 MPN variants might progress into blast-phase disease (MPN-BP). For
essential thrombocythemia, reported risk factors for leukemic transformation
include advanced age, extreme thrombocytosis, anemia, leukocytosis, and sequence
variants/mutations involving TP53 and EZH2 (for expansion of gene symbols, see
www.genenames.org); for polycythemia vera, advanced age, leukocytosis, abnormal
karyotype, mutations involving SRSF2 and IDH2, and treatment with pipobroman,
chlorambucil, or P32; and for PMF, increased blast percentage, thrombocytopenia,
abnormal karyotype, triple-negative driver mutational status, and sequence
variants/mutations involving SRSF2, RUNX1, CEBPA, and SH2B3. The reported median
survival figures for MPN-BP range from 1.5 to 2.5 months in patients treated with
supportive care only, from 2.5 to 10 months in those receiving hypomethylating
agents or low-dose chemotherapy, and from 3.9 to 9.4 months in those receiving
induction chemotherapy. Three-year survival after allogeneic stem cell transplant
was reported in 16% to 33% of patients. These observations validate the extremely
poor prognosis associated with MPN-BP and the lack of effective drug therapy and
highlight the need for urgent assessment of therapeutic values of investigational
agents. In the meantime, affected patients might be best served with aggressive
chemotherapy followed by allogeneic stem cell transplant after adequate blast
clearance.
PMID- 28688467
TI - Prediction of Response to Targeted Treatment in Rheumatoid Arthritis.
AB - Rheumatoid arthritis is an autoimmune syndrome presenting with chronic
inflammation of the joints. Patients with the same diagnosis can present with
different phenotypes. In some patients severe joint inflammation and early joint
destruction are observed, whereas a milder phenotype can be seen in others.
Conversely, patients with the same signs and symptoms may exhibit different
immunological and molecular abnormalities. Since the introduction of early
treatment in clinical practice, the treat to target principle, and new medicines
such as biologic disease-modifying antirheumatic drugs, clinical remission can be
achieved early in the disease course, albeit not in all patients. The clinical
response and efficacy of biologic disease-modifying antirheumatic drugs vary
among different individuals. Therefore, there is a need to develop a more
personalized approach toward treatment to achieve rapid remission in every
patient to prevent disability and restore and maintain quality of life, without
unnecessary adverse effects, in a cost-effective manner. The latest data from
explorative studies of predictive markers of response are discussed here,
together with a preliminary treatment algorithm based on currently available
knowledge.
PMID- 28688469
TI - Financial Conflict of Interest and Academic Influence Among Experts Speaking on
Behalf of the Pharmaceutical Industry at the US Food and Drug Administration's
Oncologic Drugs Advisory Committee Meetings.
PMID- 28688470
TI - Bisphosphonates and Osteonecrosis of the Jaw.
PMID- 28688468
TI - Evaluation and Management of Atherosclerotic Carotid Stenosis.
AB - Medical therapies for the prevention of stroke have advanced considerably in the
past several years. There can also be a role for mechanical restoration of the
lumen by endarterectomy or stenting in selected patients with high-grade
atherosclerotic stenosis of the extracranial carotid artery. Endarterectomy is
generally recommended for patients with high-grade symptomatic carotid stenosis.
Stenting is considered an option for patients at high risk of complications with
endarterectomy. Whether revascularization is better than contemporary medical
therapy for asymptomatic extracranial carotid stenosis is a subject of several
ongoing randomized clinical trials in the United States and internationally.
PMID- 28688471
TI - Dose-Response Relationship Between Severe Hypercholesterolemia and Body Mass
Index in Healthy Young Adults.
PMID- 28688472
TI - In Reply-Bisphosphonates and Osteonecrosis of the Jaw.
PMID- 28688473
TI - MYH9-Related Thrombocytopenia.
PMID- 28688474
TI - Squamous Cell Carcinoma of the Tongue.
PMID- 28688475
TI - Adolf Lorenz - The Bloodless Surgeon of Vienna.
PMID- 28688476
TI - East River and East River #2 by Mitchell Johnson.
AB - Recognizing the contribution art has had in the Mayo Clinic environment since the
original Mayo Clinic Building was finished in 1914, Mayo Clinic Proceedings
features some of the numerous works of art displayed throughout the buildings and
grounds on Mayo Clinic campuses as interpreted by the author.
PMID- 28688477
TI - Food allergy in childhood: Are we close to having an effective treatment?
PMID- 28688478
TI - Biomechanically driven unsteady non-uniform flow of Copper water and Silver water
nanofluids through finite length channel.
AB - BACKGROUND AND OBJECTIVES: This paper aims to investigate the unsteady flow of
two types of nanofluids i.e Copper water nanofluids and Silver water nanofluids)
through finite length non-uniform channel driven by peristaltic sinusoidal wave
propagations. METHODS: The governing equations are reduced in linear form using
dimensional analysis and considering the low Reynolds number and large wavelength
approximations. The time dependent temperature field, axial velocity, transverse
velocity and pressure difference are obtained analytically in closed form
solution. Trapping phenomenon is also discussed with the help of contour plots of
stream function. A comparative study of pure water (Newtonian fluid), Copper
water nanofluids and Silver water nanofluids under the influence of relevant
physical parameters is made in graphical form and also discussed. The effects of
absorption parameter and Grashof number on velocity profiles, temperature
profiles and pressure distribution along the length of channel are examined.
RESULTS CONCLUSIONS: The computational results reveal that the velocity profile
is maximum for Silver water nanofluids however, it is least for Copper water
nanofluids. It is also concluded the temperature profile is more for pure water
in comparison to Silver water and Copper water nanofluids. This model is
applicable to design, micro-peristaltic pumps which help in Nanoparticle-based
targeted drug delivery and to transport the sensitive or corrosive fluids,
sanitary fluids, slurries and noxious fluids in nuclear industry.
PMID- 28688479
TI - Physiological closed-loop control in intelligent oxygen therapy: A review.
AB - BACKGROUND AND OBJECTIVE: Oxygen therapy has become a standard care for the
treatment of patients with chronic obstructive pulmonary disease and other
hypoxemic chronic lung diseases. In current systems, manually continuous
adjustment of O2 flow rate is a time-consuming task, often unsuccessful, that
requires experienced staff. The primary aim of this systematic review is to
collate and report on the principles, algorithms and accuracy of autonomous
physiological close-loop controlled oxygen devices as well to present
recommendations for future research and studies in this area. METHODS: A
literature search was performed on medical database MEDLINE, engineering database
IEEE-Xplore and wide-raging scientific databases Scopus and Web of Science. A
narrative synthesis of the results was carried out. RESULTS: A summary of the
findings of this review suggests that when compared to the conventional manual
practice, the closed-loop controllers maintain higher saturation levels, spend
less time below the target saturation, and save oxygen resources. Nonetheless,
despite of their potential, autonomous oxygen therapy devices are scarce in real
clinical applications. CONCLUSIONS: Robustness of control algorithms, fail-safe
mechanisms, limited reliability of sensors, usability issues and the need for
standardized evaluating methods of assessing risks can be among the reasons for
this lack of matureness and need to be addressed before the wide spreading of a
new generation of automatic oxygen devices.
PMID- 28688480
TI - An intelligent support system for automatic detection of cerebral vascular
accidents from brain CT images.
AB - OBJECTIVE: This paper presents a Radial Basis Functions Neural Network (RBFNN)
based detection system, for automatic identification of Cerebral Vascular
Accidents (CVA) through analysis of Computed Tomographic (CT) images. METHODS:
For the design of a neural network classifier, a Multi Objective Genetic
Algorithm (MOGA) framework is used to determine the architecture of the
classifier, its corresponding parameters and input features by maximizing the
classification precision, while ensuring generalization. This approach considers
a large number of input features, comprising first and second order pixel
intensity statistics, as well as symmetry/asymmetry information with respect to
the ideal mid-sagittal line. RESULTS: Values of specificity of 98% and
sensitivity of 98% were obtained, at pixel level, by an ensemble of non-dominated
models generated by MOGA, in a set of 150 CT slices (1,867,602pixels), marked by
a NeuroRadiologist. This approach also compares favorably at a lesion level with
three other published solutions, in terms of specificity (86% compared with 84%),
degree of coincidence of marked lesions (89% compared with 77%) and
classification accuracy rate (96% compared with 88%).
PMID- 28688481
TI - Examining applying high performance genetic data feature selection and
classification algorithms for colon cancer diagnosis.
AB - BACKGROUND AND OBJECTIVES: This paper examines the accuracy and efficiency (time
complexity) of high performance genetic data feature selection and classification
algorithms for colon cancer diagnosis. The need for this research derives from
the urgent and increasing need for accurate and efficient algorithms. Colon
cancer is a leading cause of death worldwide, hence it is vitally important for
the cancer tissues to be expertly identified and classified in a rapid and timely
manner, to assure both a fast detection of the disease and to expedite the drug
discovery process. METHODS: In this research, a three-phase approach was proposed
and implemented: Phases One and Two examined the feature selection algorithms and
classification algorithms employed separately, and Phase Three examined the
performance of the combination of these. RESULTS: It was found from Phase One
that the Particle Swarm Optimization (PSO) algorithm performed best with the
colon dataset as a feature selection (29 genes selected) and from Phase Two that
the Support Vector Machine (SVM) algorithm outperformed other classifications,
with an accuracy of almost 86%. It was also found from Phase Three that the
combined use of PSO and SVM surpassed other algorithms in accuracy and
performance, and was faster in terms of time analysis (94%). CONCLUSIONS: It is
concluded that applying feature selection algorithms prior to classification
algorithms results in better accuracy than when the latter are applied alone.
This conclusion is important and significant to industry and society.
PMID- 28688482
TI - Enhancing automatic closed-loop glucose control in type 1 diabetes with an
adaptive meal bolus calculator - in silico evaluation under intra-day
variability.
AB - BACKGROUND AND OBJECTIVE: Current prototypes of closed-loop systems for glucose
control in type 1 diabetes mellitus, also referred to as artificial pancreas
systems, require a pre-meal insulin bolus to compensate for delays in
subcutaneous insulin absorption in order to avoid initial post-prandial
hyperglycemia. Computing such a meal bolus is a challenging task due to the high
intra-subject variability of insulin requirements. Most closed-loop systems
compute this pre-meal insulin dose by a standard bolus calculation, as is
commonly found in insulin pumps. However, the performance of these calculators is
limited due to a lack of adaptiveness in front of dynamic changes in insulin
requirements. Despite some initial attempts to include adaptation within these
calculators, challenges remain. METHODS: In this paper we present a new technique
to automatically adapt the meal-priming bolus within an artificial pancreas. The
technique consists of using a novel adaptive bolus calculator based on Case-Based
Reasoning and Run-To-Run control, within a closed-loop controller. Coordination
between the adaptive bolus calculator and the controller was required to achieve
the desired performance. For testing purposes, the clinically validated Imperial
College Artificial Pancreas controller was employed. The proposed system was
evaluated against itself but without bolus adaptation. The UVa-Padova T1DM v3.2
system was used to carry out a three-month in silico study on 11 adult and 11
adolescent virtual subjects taking into account inter-and intra-subject
variability of insulin requirements and uncertainty on carbohydrate intake.
RESULTS: Overall, the closed-loop controller enhanced by an adaptive bolus
calculator improves glycemic control when compared to its non-adaptive
counterpart. In particular, the following statistically significant improvements
were found (non-adaptive vs. adaptive). Adults: mean glucose 142.2 +/- 9.4vs.
131.8 +/- 4.2mg/dl; percentage time in target [70, 180]mg/dl, 82.0 +/- 7.0vs.
89.5 +/- 4.2; percentage time above target 17.7 +/- 7.0vs. 10.2 +/- 4.1.
Adolescents: mean glucose 158.2 +/- 21.4vs. 140.5 +/- 13.0mg/dl; percentage time
in target, 65.9 +/- 12.9vs. 77.5 +/- 12.2; percentage time above target, 31.7 +/-
13.1vs. 19.8 +/- 10.2. Note that no increase in percentage time in hypoglycemia
was observed. CONCLUSION: Using an adaptive meal bolus calculator within a closed
loop control system has the potential to improve glycemic control in type 1
diabetes when compared to its non-adaptive counterpart.
PMID- 28688483
TI - Imaging of heart acoustic based on the sub-space methods using a microphone
array.
AB - BACKGROUND AND OBJECTIVES: Heart disease is one of the leading causes of death
around the world. Phonocardiogram (PCG) is an important bio-signal which
represents the acoustic activity of heart, typically without any spatiotemporal
information of the involved acoustic sources. The aim of this study is to analyze
the PCG by employing a microphone array by which the heart internal sound sources
could be localized, too. METHOD: In this paper, it is intended to propose a
modality by which the locations of the active sources in the heart could also be
investigated, during a cardiac cycle. In this way, a microphone array with six
microphones is employed as the recording set up to be put on the human chest. In
the following, the Group Delay MUSIC algorithm which is a sub-space based
localization method is used to estimate the location of the heart sources in
different phases of the PCG. RESULTS: We achieved to 0.14cm mean error for the
sources of first heart sound (S1) simulator and 0.21cm mean error for the sources
of second heart sound (S2) simulator with Group Delay MUSIC algorithm. The
acoustical diagrams created for human subjects show distinct patterns in various
phases of the cardiac cycles such as the first and second heart sounds. Moreover,
the evaluated source locations for the heart valves are matched with the ones
that are obtained via the 4-dimensional (4D) echocardiography applied, to a real
human case. CONCLUSIONS: Imaging of heart acoustic map presents a new outlook to
indicate the acoustic properties of cardiovascular system and disorders of valves
and thereby, in the future, could be used as a new diagnostic tool.
PMID- 28688484
TI - Computer-aided prediction of axillary lymph node status in breast cancer using
tumor surrounding tissue features in ultrasound images.
AB - BACKGROUND AND OBJECTIVE: The presence or absence of axillary lymph node (ALN)
metastasis is the most important prognostic factor for patients with early-stage
breast cancer. In this study, a computer-aided prediction (CAP) system using the
tumor surrounding tissue features in ultrasound (US) images was proposed to
determine the ALN status in breast cancer. METHODS: The US imaging database used
in this study contained 114 cases of invasive breast cancer and 49 of them were
ALN metastasis. After the tumor region segmentation by the level set method,
image matting method was used to extract surrounding abnormal tissue of tumor
from the acquired images. Then, 21 features composed of 2 intensity, 3
morphology, and 16 textural features are extracted from the surrounding tissue
and processed by a logistic regression model. Finally, the prediction model is
trained and tested from the selected features. RESULTS: In the experiments, the
textural feature set extracted from surrounding tissue showed higher performance
than intensity and morphology feature sets (Az, 0.7756 vs 0.7071 and 0.6431). The
accuracy, sensitivity, specificity and the area index Az under the receiver
operating characteristic (ROC) curve for the CAP system were 81.58% (93/114),
81.63% (40/49), 81.54% (53/65), and 0.8269 for using combined feature set.
CONCLUSIONS: These results indicated that the proposed CAP system can be helpful
to determine the ALN status in patients with breast cancer.
PMID- 28688485
TI - Continuous detection of human fall using multimodal features from Kinect sensors
in scalable environment.
AB - BACKGROUND AND OBJECTIVES: Automatic detection of human fall is a key problem in
video surveillance and home monitoring. Existing methods using unimodal data (RGB
/ depth / skeleton) may suffer from the drawbacks of inadequate lighting
condition or unreliability. Besides, most of proposed methods are constrained to
a small space with off-line video stream. METHODS: In this study, we overcome
these encountered issues by combining multi-modal features (skeleton and RGB)
from Kinect sensor to take benefits of each data characteristic. If a skeleton is
available, we propose a rules based technique on the vertical velocity and the
height to floor plane of the human center. Otherwise, we compute a motion map
from a continuous gray-scale image sequence, represent it by an improved kernel
descriptor then input to a linear Support Vector Machine. This combination speeds
up the proposed system and avoid missing detection at an unmeasurable range of
the Kinect sensor. We then deploy this method with multiple Kinects to deal with
large environments based on client server architecture with late fusion
techniques. RESULTS: We evaluated the method on some freely available datasets
for fall detection. Compared to recent methods, our method has a lower false
alarm rate while keeping the highest accuracy. We also validated on-line our
system using multiple Kinects in a large lab-based environment. Our method
obtained an accuracy of 91.5% at average frame-rate of 10fps. CONCLUSIONS: The
proposed method using multi-modal features obtained higher results than using
unimodal features. Its on-line deployment on multiple Kinects shows the potential
to be applied in to any of living space in reality.
PMID- 28688486
TI - Corrigendum to "DISTING: A web application for fast algorithmic computation of
alternative indistinguishable linear compartmental models" [Computer Methods and
Programs in Biomedicine 143 (2017) 129-135].
PMID- 28688487
TI - Development of an expert system for the simulation model for casting metal
substructure of a metal-ceramic crown design.
AB - BACKGROUND AND OBJECTIVES: Nowadays, the integrated CAD/CAE systems are favored
solutions for the design of simulation models for casting metal substructures of
metal-ceramic crowns. The worldwide authors have used different approaches to
solve the problems using an expert system. Despite substantial research progress
in the design of experts systems for the simulation model design and
manufacturing have insufficiently considered the specifics of casting in
dentistry, especially the need for further CAD, RE, CAE for the estimation of
casting parameters and the control of the casting machine. The novel expert
system performs the following: CAD modeling of the simulation model for casting,
fast modeling of gate design, CAD eligibility and cast ability check of the
model, estimation and running of the program code for the casting machine, as
well as manufacturing time reduction of the metal substructure. METHODS: The
authors propose an integration method using common data model approach,
blackboard architecture, rule-based reasoning and iterative redesign method.
Arithmetic mean roughness values was determinated with constant Gauss low-pass
filter (cut-off length of 2.5mm) according to ISO 4287 using Mahr MARSURF PS1.
Dimensional deviation between the designed model and manufactured cast was
determined using the coordinate measuring machine Zeiss Contura G2 and GOM
Inspect software. RESULTS: The ES allows for obtaining the castings derived
roughness grade number N7. The dimensional deviation between the simulation model
of the metal substructure and the manufactured cast is 0.018mm. The arithmetic
mean roughness values measured on the casting substructure are from 1.935um to
2.778um. CONCLUSIONS: The realized developed expert system with the integrated
database is fully applicable for the observed hardware and software. Values of
the arithmetic mean roughness and dimensional deviation indicate that casting
substructures are surface quality, which is more than enough and useful for
direct porcelain veneering. The manufacture of the substructure shows that the
proposed ES allows the improvement of the design process while reducing the
manufacturing time.
PMID- 28688488
TI - Support for Taverna workflows in the VPH-Share cloud platform.
AB - BACKGROUND AND OBJECTIVE: To address the increasing need for collaborative
endeavours within the Virtual Physiological Human (VPH) community, the VPH-Share
collaborative cloud platform allows researchers to expose and share sequences of
complex biomedical processing tasks in the form of computational workflows. The
Taverna Workflow System is a very popular tool for orchestrating complex
biomedical & bioinformatics processing tasks in the VPH community. This paper
describes the VPH-Share components that support the building and execution of
Taverna workflows, and explains how they interact with other VPH-Share components
to improve the capabilities of the VPH-Share platform. METHODS: Taverna workflow
support is delivered by the Atmosphere cloud management platform and the VPH
Share Taverna plugin. These components are explained in detail, along with the
two main procedures that were developed to enable this seamless integration:
workflow composition and execution. RESULTS: 1) Seamless integration of VPH-Share
with other components and systems. 2) Extended range of different tools for
workflows. 3) Successful integration of scientific workflows from other VPH
projects. 4) Execution speed improvement for medical applications. CONCLUSION:
The presented workflow integration provides VPH-Share users with a wide range of
different possibilities to compose and execute workflows, such as desktop or
online composition, online batch execution, multithreading, remote execution,
etc. The specific advantages of each supported tool are presented, as are the
roles of Atmosphere and the VPH-Share plugin within the VPH-Share project. The
combination of the VPH-Share plugin and Atmosphere engenders the VPH-Share
infrastructure with far more flexible, powerful and usable capabilities for the
VPH-Share community. As both components can continue to evolve and improve
independently, we acknowledge that further improvements are still to be developed
and will be described.
PMID- 28688489
TI - A PCA aided cross-covariance scheme for discriminative feature extraction from
EEG signals.
AB - BACKGROUND AND OBJECTIVES: Feature extraction of EEG signals plays a significant
role in Brain-computer interface (BCI) as it can significantly affect the
performance and the computational time of the system. The main aim of the current
work is to introduce an innovative algorithm for acquiring reliable
discriminating features from EEG signals to improve classification performances
and to reduce the time complexity. METHODS: This study develops a robust feature
extraction method combining the principal component analysis (PCA) and the cross
covariance technique (CCOV) for the extraction of discriminatory information from
the mental states based on EEG signals in BCI applications. We apply the
correlation based variable selection method with the best first search on the
extracted features to identify the best feature set for characterizing the
distribution of mental state signals. To verify the robustness of the proposed
feature extraction method, three machine learning techniques: multilayer
perceptron neural networks (MLP), least square support vector machine (LS-SVM),
and logistic regression (LR) are employed on the obtained features. The proposed
methods are evaluated on two publicly available datasets. Furthermore, we
evaluate the performance of the proposed methods by comparing it with some
recently reported algorithms. RESULTS: The experimental results show that all
three classifiers achieve high performance (above 99% overall classification
accuracy) for the proposed feature set. Among these classifiers, the MLP and LS
SVM methods yield the best performance for the obtained feature. The average
sensitivity, specificity and classification accuracy for these two classifiers
are same, which are 99.32%, 100%, and 99.66%, respectively for the BCI
competition dataset IVa and 100%, 100%, and 100%, for the BCI competition dataset
IVb. The results also indicate the proposed methods outperform the most recently
reported methods by at least 0.25% average accuracy improvement in dataset IVa.
The execution time results show that the proposed method has less time complexity
after feature selection. CONCLUSIONS: The proposed feature extraction method is
very effective for getting representatives information from mental states EEG
signals in BCI applications and reducing the computational complexity of
classifiers by reducing the number of extracted features.
PMID- 28688490
TI - A fourth order PDE based fuzzy c- means approach for segmentation of microscopic
biopsy images in presence of Poisson noise for cancer detection.
AB - BACKGROUND AND OBJECTIVE: For cancer detection from microscopic biopsy images,
image segmentation step used for segmentation of cells and nuclei play an
important role. Accuracy of segmentation approach dominate the final results.
Also the microscopic biopsy images have intrinsic Poisson noise and if it is
present in the image the segmentation results may not be accurate. The objective
is to propose an efficient fuzzy c-means based segmentation approach which can
also handle the noise present in the image during the segmentation process itself
i.e. noise removal and segmentation is combined in one step. METHODS: To address
the above issues, in this paper a fourth order partial differential equation
(FPDE) based nonlinear filter adapted to Poisson noise with fuzzy c-means
segmentation method is proposed. This approach is capable of effectively handling
the segmentation problem of blocky artifacts while achieving good tradeoff
between Poisson noise removals and edge preservation of the microscopic biopsy
images during segmentation process for cancer detection from cells. RESULTS: The
proposed approach is tested on breast cancer microscopic biopsy data set with
region of interest (ROI) segmented ground truth images. The microscopic biopsy
data set contains 31 benign and 27 malignant images of size 896 * 768. The region
of interest selected ground truth of all 58 images are also available for this
data set. Finally, the result obtained from proposed approach is compared with
the results of popular segmentation algorithms; fuzzy c-means, color k-means,
texture based segmentation, and total variation fuzzy c-means approaches.
CONCLUSIONS: The experimental results shows that proposed approach is providing
better results in terms of various performance measures such as Jaccard
coefficient, dice index, Tanimoto coefficient, area under curve, accuracy, true
positive rate, true negative rate, false positive rate, false negative rate,
random index, global consistency error, and variance of information as compared
to other segmentation approaches used for cancer detection.
PMID- 28688491
TI - Sequence based predictor for discrimination of enhancer and their types by
applying general form of Chou's trinucleotide composition.
AB - BACKGROUND AND OBJECTIVES: Enhancers are pivotal DNA elements, which are widely
used in eukaryotes for activation of transcription genes. On the basis of
enhancer strength, they are further classified into two groups; strong enhancers
and weak enhancers. Due to high availability of huge amount of DNA sequences, it
is needed to develop fast, reliable and robust intelligent computational method,
which not only identify enhancers but also determines their strength.
Considerable progress has been achieved in this regard; however, timely and
precisely identification of enhancers is still a challenging task. METHODS: Two
level intelligent computational model for identification of enhancers and their
subgroups is proposed. Two different feature extraction techniques including di
nucleotide composition and tri-nucleotide composition were adopted for extraction
of numerical descriptors. Four classification methods including probabilistic
neural network, support vector machine, k-nearest neighbor and random forest were
utilized for classification. RESULTS: The proposed method yielded 77.25% of
accuracy for dataset S1 contains enhancers and non-enhancers, whereas 64.70% of
accuracy for dataset S2 comprises of strong enhancer and weak enhancer sequences
using jackknife cross-validation test. CONCLUSION: The predictive results
validated that the proposed method is better than that of existing approaches so
far reported in the literature. It is thus highly observed that the developed
method will be useful and expedient for basic research and academia.
PMID- 28688492
TI - Quantifying the informativeness for biomedical literature summarization: An
itemset mining method.
AB - OBJECTIVE: Automatic text summarization tools can help users in the biomedical
domain to access information efficiently from a large volume of scientific
literature and other sources of text documents. In this paper, we propose a
summarization method that combines itemset mining and domain knowledge to
construct a concept-based model and to extract the main subtopics from an input
document. Our summarizer quantifies the informativeness of each sentence using
the support values of itemsets appearing in the sentence. METHODS: To address the
concept-level analysis of text, our method initially maps the original document
to biomedical concepts using the Unified Medical Language System (UMLS). Then, it
discovers the essential subtopics of the text using a data mining technique,
namely itemset mining, and constructs the summarization model. The employed
itemset mining algorithm extracts a set of frequent itemsets containing
correlated and recurrent concepts of the input document. The summarizer selects
the most related and informative sentences and generates the final summary.
RESULTS: We evaluate the performance of our itemset-based summarizer using the
Recall-Oriented Understudy for Gisting Evaluation (ROUGE) metrics, performing a
set of experiments. We compare the proposed method with GraphSum, TexLexAn,
SweSum, SUMMA, AutoSummarize, the term-based version of the itemset-based
summarizer, and two baselines. The results show that the itemset-based summarizer
performs better than the compared methods. The itemset-based summarizer achieves
the best scores for all the assessed ROUGE metrics (R-1: 0.7583, R-2: 0.3381, R-W
1.2: 0.0934, and R-SU4: 0.3889). We also perform a set of preliminary experiments
to specify the best value for the minimum support threshold used in the itemset
mining algorithm. The results demonstrate that the value of this threshold
directly affects the accuracy of the summarization model, such that a significant
decrease can be observed in the performance of summarization due to assigning
extreme thresholds. CONCLUSION: Compared to the statistical, similarity, and word
frequency methods, the proposed method demonstrates that the summarization model
obtained from the concept extraction and itemset mining provides the summarizer
with an effective metric for measuring the informative content of sentences. This
can lead to an improvement in the performance of biomedical literature
summarization.
PMID- 28688493
TI - Computer-aided diagnosis of periapical cyst and keratocystic odontogenic tumor on
cone beam computed tomography.
AB - BACKGROUND AND OBJECTIVES: In this article, we propose a decision support system
for effective classification of dental periapical cyst and keratocystic
odontogenic tumor (KCOT) lesions obtained via cone beam computed tomography
(CBCT). CBCT has been effectively used in recent years for diagnosing dental
pathologies and determining their boundaries and content. Unlike other imaging
techniques, CBCT provides detailed and distinctive information about the
pathologies by enabling a three-dimensional (3D) image of the region to be
displayed. METHODS: We employed 50 CBCT 3D image dataset files as the full
dataset of our study. These datasets were identified by experts as periapical
cyst and KCOT lesions according to the clinical, radiographic and histopathologic
features. Segmentation operations were performed on the CBCT images using viewer
software that we developed. Using the tools of this software, we marked the
lesional volume of interest and calculated and applied the order statistics and
3D gray-level co-occurrence matrix for each CBCT dataset. A feature vector of the
lesional region, including 636 different feature items, was created from those
statistics. Six classifiers were used for the classification experiments.
RESULTS: The Support Vector Machine (SVM) classifier achieved the best
classification performance with 100% accuracy, and 100% F-score (F1) scores as a
result of the experiments in which a ten-fold cross validation method was used
with a forward feature selection algorithm. SVM achieved the best classification
performance with 96.00% accuracy, and 96.00% F1 scores in the experiments in
which a split sample validation method was used with a forward feature selection
algorithm. SVM additionally achieved the best performance of 94.00% accuracy, and
93.88% F1 in which a leave-one-out (LOOCV) method was used with a forward feature
selection algorithm. CONCLUSIONS: Based on the results, we determined that
periapical cyst and KCOT lesions can be classified with a high accuracy with the
models that we built using the new dataset selected for this study. The studies
mentioned in this article, along with the selected 3D dataset, 3D statistics
calculated from the dataset, and performance results of the different
classifiers, comprise an important contribution to the field of computer-aided
diagnosis of dental apical lesions.
PMID- 28688494
TI - Automatic methods for managements of cancer, medicine, and behavior.
PMID- 28688495
TI - Optimal Cutoffs of Cardiometabolic Risk for Postmenopausal Korean Women.
AB - PURPOSE: The purpose of the study was to identify the optimal cutoff values of
indices for cardiometabolic risk in postmenopausal Korean women. Specifically, we
intended to determine the cutoffs of waist circumference, waist-to-hip ratio
(WHR), serum lipid profile, and homeostatic model of assessment-insulin
resistance (HOMA-IR) for detecting metabolic syndrome (MetS), and metabolic
obesity (MO). METHODS: The study participants were 397 postmenopausal women. We
defined MetS and MO with the International Diabetes Federation criteria except
for waist circumference. A receive operating characteristic curve analysis was
used to assess the accuracy of diagnostic indices for identifying MetS and MO.
Cutoff values were obtained both from the point on the receive operating
characteristic curve which was closest to (0,1) and from the Youden's index.
RESULTS: Among the participants, 34.5% and 73% were classified as having MetS and
MO. The optimal cutoff of waist circumference and WHR were 81.9 cm [area under
curve (AUC): 0.687, sensitivity: 61.7%, specificity: 68.9%], 0.87 (AUC: 0.660,
sensitivity: 64.7%, Specificity: 60.2%) for MetS and 77.4 cm (AUC: 0.655,
sensitivity: 65.6%, specificity: 57.8%), 0.86 (AUC: 0.680, sensitivity: 67.0%,
specificity: 62.7%) for MO. Triglyceride to high-density lipoprotein ratio for
MetS and MO were 2.11 (AUC: 0.838, sensitivity: 71.5%, specificity: 79.6%) and
1.59 (AUC: 0.725, sensitivity: 65.9%, specificity: 68.2%) respectively. The HOMA
IR for MetS was 1.36 (AUC: 0.773, sensitivity: 73%, specificity: 71.9%) and for
MO was 1.17 (AUC: 0.713, sensitivity: 64.5%, specificity: 69.2%). CONCLUSIONS:
For postmenopausal women, we suggest waist circumference of 81.9 cm and WHR of
0.87 as criteria of MetS. However, women with waist circumference over 77.4 cm
and WHR over 0.86 should be monitored for the future development of MetS.
PMID- 28688496
TI - Change in Care Dependency of Stroke Patients: A Longitudinal and Multicenter
Study.
AB - PURPOSE: The study was conducted to investigate the change of care dependency in
stroke patients from inpatient wards and outpatient units in Indonesia. METHODS:
This study is longitudinal and multicentered. One hundred and nine patients were
included from four hospitals on the island of Java. Care dependency was assessed
using the Indonesian version of the 15-item Care Dependency Scale (CDS) at five
points in time: at inpatient wards for admission and discharge and at outpatient
units after discharge in the 1st week, the 5th week, and the 13th week. RESULTS:
Most of the patients were male (65.1%), and diagnosed with ischemic stroke
(71.5%). The results showed that care dependency in stroke patients decreased
significantly from admission to discharge, as well as from the 5th to the 13th
week as measured by the CDS. At admission, 23.0% of the patients were completely
dependent on care, and at the 13th week about 1.0% were. Patients' care
dependency decreased significantly in all care dependency items of the CDS in the
inpatient ward, but five care dependency items of the CDS did not significantly
decrease in the outpatient unit. CONCLUSIONS: Based on the findings of this
study, we recommend that hospital-based and community-based services should
include continual care dependence monitoring using this comprehensive instrument.
Care dependency is subject to change over time, therefore nurses have to plan and
tailor adequate nursing care measures to patient needs in the different stages,
especially with respect to the aspect of mobility.
PMID- 28688497
TI - Theory-based Osteoporosis Prevention Education and Counseling Program for Women:
A Randomized Controlled Trial.
AB - PURPOSE: The purpose of this research was to investigate the effect of an
osteoporosis prevention program based on the Health Belief Model for women
between the ages of 30 years and 45 years at risk of osteoporosis. METHODS: This
study was conducted with randomized control group pretest, post-test and follow
up trial. Intervention group (n = 37) and control group (n = 36) participated in
the research. Data were collected using a sociodemographic data questionnaire,
the Osteoporosis Knowledge Test, the Osteoporosis Health Belief Scale, the
Osteoporosis Self-efficacy Scale, a monitoring form for estimated dairy calcium
intake, and a monitoring form for estimated weekly exercise. Intervention program
was composed of a 4-week education program and a 24-week counseling program. Data
were collected pretest, post-test 15 days after the end of the education program,
follow-up 1 after 3 months, and follow-up 2 after 6 months. Mann Whitney U test,
chi-square test, Friedman test, Bonferroni test, two means test and Wilcoxon
signed-rank test were used for statistical analysis. RESULTS: After the education
and counseling program, a significant increase was seen in comparison with the
control group in the mean scores of the intervention group on the Osteoporosis
Knowledge Test and its subscales (p < .001), on the Osteoporosis Health Belief
Scale and its subscales (p < .001), on the Osteoporosis Self-efficacy Scale and
its subscales (p < .001), and in their daily calcium intake (p < .001) and
duration of weekly exercise (p < .001). CONCLUSION: The results of this study
were evidence that showed the effects of Health Belief Model-based osteoporosis
prevention education and counseling program conducted by nurses.
PMID- 28688498
TI - Turkish Version of the Student Nurse Stress Index: Validity and Reliability.
AB - PURPOSE: This study aimed to adapt the Student Nurse Stress Index (SNSI) for the
Turkish nursing students and investigate its psychometric properties. METHODS:
Research was conducted with 152 volunteer female students who attended a
university college in Ankara, Turkey. Test-retest reliability was investigated
for the scale internal consistency (Cronbach alpha) and stability. Also, content
validity and construct validity of the SNSI were assessed. In order to determine
the construct validity of SNSI, Uygulamali Cok Degiskenli Istatistiksel Yontemler
and confirmatory factor analysis was conducted. RESULTS: The Turkish version of
SNSI with 15 items comprised four factors (academic load, clinical concerns,
personal problems, interface worries). The content validity index (CVI) score was
.97. Factor loadings of Turkish version of SNSI varied between .532 and .868. The
"personal problems" subscale explained 19.01% of the variance; "clinical
concerns" explained 18.51%; "interface worries" explained 15.32%; "academic load"
explained 14.14%. The total variance explained was 66.99%. CFA results (chi2/SD,
GFI, CFI, TLI, IFI, RMSEA and SRMR) were acceptable and in good agreement. The
internal consistency coefficient of the SNSI was .86. CONCLUSION: Results showed
that the SNSI had a satisfactory level of reliability and validity in nursing
students in Turkey. Multicenter studies including nursing students from different
nursing schools are recommended for the SNSI to be generalized.
PMID- 28688499
TI - Moderated Mediation Effect of Self-esteem on the Relationship Between Parenting
Stress and Depression According to Employment Status in Married Women: A
Longitudinal Study Utilizing Data from Panel Study on Korean Children.
AB - PURPOSE: This study was to examined the moderated mediation effect of self-esteem
on the relationship between parenting stress and depression among married women
with children using longitudinal data from the 3rd to 6th Panel Studies on
Korean. METHODS: The data from the Panel Study of Korean Children (Korea
Institute of Child Care and Education) was collected as part of a longitudinal
inquiry of babies born in 2008, their parents and their community environments.
Only the data collected from the married women over the age of 20 who
participated in the maternal survey was used for this study. RESULTS: The initial
level of married women's parenting stress affects the initial level and the rate
of change in self-esteem; the initial level of self-esteem, the initial level and
rate of change in depression; and the initial level of parenting stress, the
initial level of depression. However, the impact of the rate of change in
parenting stress on that of self-esteem was significant only in employed women
while the impact of the rate of change in self-esteem on that of depression was
significant only in unemployed women. CONCLUSION: It is necessary to manage
parenting stress among married women through various programs and education that
increase self-esteem in order to reduce their level of depression.
PMID- 28688500
TI - The Effects of Korean Medical Service Quality and Satisfaction on Revisit
Intention of the United Arab Emirates Government Sponsored Patients.
AB - PURPOSE: The purpose of this study was to investigate medical service quality,
satisfaction and to examine factors influencing hospital revisit intention of the
United Arab Emirates government sponsored patients in Korea. METHODS: A total of
152 UAE government sponsored patients who visited Korean hospitals participated
in the questionnaire survey from August to November 2016. Stepwise multiple
regression was used to identify the factors that affected the revisit intention
of the participants. RESULTS: The mean scores of medical service quality,
satisfaction, and revisit intention were 5.72 out of 7, 88.88 out of 100, 4.59
out of 5, respectively. Medical service quality and satisfaction, Medical service
quality and revisit intention, satisfaction and revisit intention were positively
correlated. Medical service of physician, visiting routes and responsiveness of
medical service quality explained about 23.8% of revisit intention. CONCLUSIONS:
There are needs for physicians to communicate with patients while ensuring
sufficient consultation time based on excellent medical skills and nurses to
respond immediately for the patients' needs through an empathic encounter in
order to improve medical service quality and patient satisfaction so that to
increase the revisit intention of the United Arab Emirates government sponsored
patients. Further, it is necessary for the hospitals to have support plans for
providing country specialized services in consideration of the UAE culture to
ensure that physicians' and nurses' competencies are not undervalued by non
medical service elements such as interpreters and meals.
PMID- 28688501
TI - A Community Based Program for Family Caregivers for Post Stroke Survivors in
Thailand.
AB - PURPOSE: The purpose of this study was to evaluate the effectiveness of the post
stroke care program within the community setting in Thailand. METHODS: This quasi
experimental study was a nonequivalent control group pre-test and post-test
design. A total of 62 pairs of post-stroke patients and their family caregivers
were recruited to the study (31 pairs per group). The intervention consisted of a
four-week program that included distributing pertinent information, providing
skill practice during post-stroke care sessions and utilizing strategies to
enhance motivation and behavioral skills of family caregivers based on the
information-motivation-behavioral skills model. The family caregivers' post
stroke care skills were evaluated. The patients' activities of daily living
(ADLs) and complications were evaluated at baseline and immediately and 2-month
post-intervention. Statistical analysis included chi-square test, Fisher's exact
test, independent t-test, and two-way repeated measures' analysis of variance.
RESULTS: After participating in the program, family caregivers in the
experimental group significantly improved their post-stroke care knowledge and
skills as compared to those in the control group (F = 585.81, p < .001). ADLs
among post-stroke patients in the experimental group significantly increased over
time and were higher than those in the control group (F = 46.01, p < .001).
Moreover, complications among patients in the experimental group were less than
those in the control group. CONCLUSIONS: The post-stroke care program improved
family caregivers' post-stroke care skills which resulted in improved functional
status and decreased complications among post-stroke patients.
PMID- 28688502
TI - Corrigendum to Nurses' Educational Needs Assessment for Financial Management
Education Using the Nominal Group Technique [Asian Nursing Research (2015) 152
157].
PMID- 28688503
TI - Recent Research Trends in Meta-analysis.
AB - The use of meta-analysis (MA), which is placed on top of the evidence hierarchy,
in studies has been increasing exponentially. MA has three effect size families.
Using the category of effect size families, this paper introduces the important
points in the MA process and highlights the recent research trends in this field,
such as network MA, meta-analytic structural equation modeling, and diagnostic
test accuracy MA. Several reporting standards were established for primary
studies and MA. The critical assessment reviews demonstrated that the current
quality of nursing MA reporting was low. The problematic areas of the current
nursing MA include study search, study selection, risk of bias, publication bias,
and additional analysis based on quality assessment. Directions for future
research are also presented in this paper.
PMID- 28688504
TI - Effects of an Adolescent Obesity Management Educational Program on Middle and
High School Teachers in South Korea.
AB - PURPOSE: This study aimed to examine the effects of an adolescent obesity
management educational program (AOMEP) on middle and high school teachers.
METHODS: A quasiexperimental, pretest post-test design was performed to test
primary variables, including adolescent obesity management knowledge, attitudes,
perceived behavioral control, and behavioral intention based on the concepts
presented in the Theory of Planned Behavior. RESULTS: A total of 61 teachers
participated. The experimental group (n = 30) received 15 hours of AOMEP, whereas
the control group (n = 31) did not receive any. The experimental group showed
significant improvement in knowledge (t = 2.53, d = .65, p = .014) and attitude
(t = 2.77, d = .71, p = .008) toward adolescent obesity management compared to
the control group. However, there were no significant differences in perceived
behavioral control or behavioral intention between the groups. CONCLUSIONS: AOMEP
may be utilized as an effective obesity management program for adolescent
students in schools.
PMID- 28688505
TI - Structural Equation Model of Smartphone Addiction Based on Adult Attachment
Theory: Mediating Effects of Loneliness and Depression.
AB - PURPOSE: This study investigated the mediating effects of loneliness and
depression on the relationship between adult attachment and smartphone addiction
in university students. METHODS: A total of 200 university students participated
in this study. The data was analysed using descriptive statistics, correlation
analysis, and structural equation modeling. RESULTS: There were significant
positive relationships between attachment anxiety, loneliness, depression, and
smartphone addiction. However, attachment anxiety was not significantly
correlated with smartphone addiction. The results also showed that loneliness did
not directly mediate between attachment anxiety and smartphone addiction. In
addition, loneliness and depression serially mediated between attachment anxiety
and smartphone addiction. CONCLUSION: The results suggest there are mediating
effects of loneliness and depression in the relationship between attachment
anxiety and smartphone addiction. The hypothesized model was found to be a
suitable model for predicting smartphone addiction among university students.
Future study is required to find a causal path to prevent smartphone addiction
among university students.
PMID- 28688506
TI - Development of the Korean Paternal-Fetal Attachment Scale (K-PAFAS).
AB - PURPOSE: This study is a methodological study aimed to develop the Korean
Paternal-Fetal Attachment Scale (K-PAFAS) to measure the level of attachment
between the father and the expected baby, and to examine its validity and
reliability. METHODS: The K-PAFAS was developed in four steps. The first step
involved derivation of the initial items through review of the literature and in
depth interviews with 10 expectant fathers. The second step was the process of
expert panel review, examining content validity for the initial items. In the
third step, items were examined for their usability through a preliminary survey
with 30 expectant fathers. As the last step, the final K-PAFAS was applied to 200
participants and examined for its psychometric profile. RESULTS: K-PAFAS
consisted of 20 items, and used a 5-point Likert scale with the total score
ranging from 20 points to 100 points. A higher score indicated a higher level of
attachment between the father and his unborn child. The K-PAFAS was composed of
four factors. The K-PAFAS demonstrated satisfactory criterion validity, which was
supported by its significant correlations with the Paternal Antenatal Attachment
Scale, the Korean Dyadic Adjustment Scale, and the Center for Epidemiological
Studies-Depression Scale. The Cronbach alpha of the K-PAFAS was .89. In test
retest reliability, the K-PAFAS showed a correlation coefficient of .91.
CONCLUSION: The K-PAFAS demonstrated initial validity and reliability. It was
short, and relatively easy for use in evaluating the degree of paternal-fetal
attachment in the antenatal management stage.
PMID- 28688507
TI - Double Hatchet Flap for the Reconstruction of Scalp Defects.
PMID- 28688508
TI - Fissure sealants and fluoride varnish were not different in terms of their
effectiveness in preventing dental caries in permanent first molars.
PMID- 28688509
TI - Preoperative prednisolone and ketorolac may result in a small reduction of
postoperative endodontic pain compared with placebo.
PMID- 28688510
TI - Insufficient evidence to claim that photodynamic therapy as an adjunct to scaling
and root planing improves periodontal parameters compared with adjunctive
antibiotics.
PMID- 28688511
TI - Laser use may improve pain and wound healing in patients with recurrent aphtous
stomatitis.
PMID- 28688512
TI - Insufficient evidence about benefits of antimicrobial photodynamic therapy as an
adjunct to mechanic curettage in smokers with peri-implant mucositis.
PMID- 28688513
TI - Good clinical outcomes at 5 years for immediately loaded implants placed using
computer-assisted surgery to support fixed complete dentures.
PMID- 28688514
TI - Pain control with continuous infusion preperitoneal wound catheters versus
continuous epidural analgesia in colon and rectal surgery: A randomized
controlled trial.
AB - OBJECTIVE: To compare continuous infusion preperitoneal wound catheters (CPA)
versus continuous epidural analgesia (CEA) after elective colorectal surgery.
METHODS: An open-label equivalence trial randomizing patients to CPA or CEA.
Primary outcomes were postoperative pain as determined by numeric pain scores and
supplemental narcotic analgesia requirements. Secondary outcomes included
incidence of complications and patient health status measured with the SF-36
Health Survey (Acute Form). RESULTS: 98 patients were randomized [CPA (N = 50,
51.0%); CEA (N = 48, 49.0%)]. 90 patients were included [ CPA 46 (51.1%); CEA 44
(48.9%)]. Pain scores were significantly higher in the CPA group in the PACU (p =
0.04) and on the day of surgery (p < 0.01) as well as supplemental narcotic
requirements on POD 0 (p = 0.02). No significant differences were noted in
postoperative complications between groups, aggregate SF-36 scores and SF-36
subscale scores. CONCLUSIONS: Continuous epidural analgesia provided superior
pain control following colorectal surgery in the PACU and on the day of surgery.
The secondary endpoints of return of bowel function, length of stay, and adjusted
SF-36 were not affected by choice of peri-operative pain control.
PMID- 28688515
TI - The triple impact of nursing.
PMID- 28688516
TI - Pancreas transplantation: Advantages of a retroperitoneal graft position.
AB - INTRODUCTION: In the 50 years since the first pancreas transplant performed at
the University of Minnesota, the surgical techniques employed have undergone many
modifications. Techniques such as retroperitoneal graft placement have further
improved the ability to reproduce the physiology of the "native" pancreas. We
herein present our experience of a modified technique for pancreatic transplant,
with the organ placed into a fully retroperitoneal position with systemic venous
and enteric drainage of the graft by duodeno-duodenostomy. METHODS: All pancreas
transplantations performed between May 2016 and January 2017 were prospectively
entered into our transplant database and retrospectively analyzed. RESULTS: A
total of 10 transplants were performed using the retroperitoneal technique (6
men: median age of 41 years [IQR 36-54]). Median cold ischemia times was 10,30h
[IQR 5,30-12,10]. The preservation solution used was Celsior (n=7), IGL-1 (n=2),
and UW (n=1). No complications related to the new surgical technique were
identified. In one patient, transplantectomy at 12h was performed due to graft
thrombosis, probably related to ischemic conditions from a donor with prolonged
cardio-respiratory arrest. Another procedure was aborted without completing the
graft implant due to an intraoperative immediate arterial thrombosis in a patient
with severe iliac atheromatosis. No primary pancreas non-function occurred in the
remaining 8patients. The median hospital stay was 13,50 days [IQR 10-27].
CONCLUSIONS: Retroperitoneal graft placement appears feasible with easy access
for dissection the vascular site; comfortable technical vascular reconstruction;
and a decreased risk of intestinal obstruction by separation of the small bowel
from the pancreas graft.
PMID- 28688517
TI - Dietary intake of Deepwater Horizon oil-injected live food fish by double-crested
cormorants resulted in oxidative stress.
AB - The Deepwater Horizon oil spill released 134 million gallons of crude oil into
the Gulf of Mexico making it the largest oil spill in US history and exposing
fish, birds, and marine mammals throughout the Gulf of Mexico to its toxicity.
Fish eating waterbirds such as the double-crested cormorant (Phalacrocorax
auritus) were exposed to the oil both by direct contact with the oil and orally
through preening and the ingestion of contaminated fish. This study investigated
the effects of orally ingestedMC252 oil-contaminated live fish food by double
crested cormorants on oxidative stress. Total, reduced, and oxidized glutathione
levels, superoxide dismutase and glutathione peroxidase activities, total
antioxidant capacity and lipid peroxidation were assessed in the liver tissues of
control and treated cormorants. The results suggest that ingestion of the oil
contaminated fish resulted in significant increase in oxidative stress in the
liver tissues of these birds. The oil-induced increase in oxidative stress could
have detrimental impacts on the bird's life-history.
PMID- 28688518
TI - Neutrophil-to-lymphocyte ratio predicts prognosis after neoadjuvant chemotherapy
and resection of intrahepatic cholangiocarcinoma.
AB - BACKGROUND: Previous studies have demonstrated a strong association between the
preoperative neutrophil-to-lymphocyte ratio and the outcomes of patients with
resected hepatocellular carcinoma and colorectal liver metastases. However, the
predictive ability of neutrophil-to-lymphocyte ratio in patients with
intrahepatic cholangiocarcinoma, especially those treated with preoperative
chemotherapy, has been less well described. METHODS: The clinicopathological
characteristics, overall survival, and recurrence free survival of all patients
with intrahepatic cholangiocarcinoma resected between 2000-2015, were compared
between those with elevated (>=3.0) and normal (<3.0) neutrophil-to-lymphocyte
ratio. RESULTS: Among 119 patients who met the inclusion criteria, 64 (53.8%) had
neutrophil-to-lymphocyte ratio <3.0 and 55 (46.2%) had neutrophil-to-lymphocyte
ratio >=3.0. Patients with neutrophil-to-lymphocyte ratio >=3.0 were more likely
to be female and have lymph node metastasis (P < .05). Cumulative 5-year overall
survival and recurrence free survival rates were 87% and 60%, respectively in
patients with neutrophil-to-lymphocyte ratio <3.0, compared with 64% and 39%,
respectively in patients with neutrophil-to-lymphocyte ratio >=3.0 (P = .049 and
.038). Among 43 patients treated with preoperative chemotherapy and resection, 21
(48.8%) had neutrophil-to-lymphocyte ratio <3.0 and 22 (51.2%) had neutrophil-to
lymphocyte ratio >=3.0. In this subgroup, cumulative 5-year overall survival and
recurrence free survival rates were 95% and 70%, respectively in the patients
with neutrophil-to-lymphocyte ratio <3.0 compared with 50% and 26%, respectively
in the patients with neutrophil-to-lymphocyte ratio >=3.0 (P = .002 and P =
.004). On multivariate analysis, a neutrophil-to-lymphocyte ratio >=3.0 was
associated significantly with worse overall survival among all patients as well
as overall survival and recurrence free survival among the subgroup who received
preoperative chemotherapy. CONCLUSION: Neutrophil-to-lymphocyte ratio is
associated independently with worse survival in patients with intrahepatic
cholangiocarcinoma undergoing resection or neoadjuvant chemotherapy prior to
resection.
PMID- 28688519
TI - Comparative assessment of in-hospital trauma mortality at a South African trauma
center and matched patients treated in the United States.
AB - BACKGROUND: The unacceptably high rate of death and disability due to injury in
Sub-Saharan Africa is alarming. The objective of this work was to compare
mortality rates between severely injured trauma patients at a high-volume trauma
center in South Africa with matched patients in the United States. METHODS:
Clinical databases from the Groote Schuur Hospital for patients treated in Cape
Town, South Africa and the American College of Surgeon's National Trauma Databank
for patients treated at large academic trauma centers in the United States were
used. Coarsened exact matching identified the most comparable patient populations
based on sex, age, intent, injury type, injury mechanism, Injury Severity Score,
Glasgow Coma Score, and systolic blood pressure. Conditional logistic regression
generated odds ratios for mortality among the entire sample and clinically
relevant subgroups. RESULTS: Coarsened exact matching matched 97.9% of the Groote
Schuur Hospital patient sample, resulting in 3,206 matched-pairs between the
Groote Schuur Hospital and National Trauma Databank cohorts. Conditional logistic
regression revealed an odds ratio of mortality of 1.67 (95% confidence interval,
1.10-2.52) for patients at Groote Schuur Hospital compared with matched patients
from the National Trauma Databank. Subset analyses revealed significantly
increased odds of mortality among patients with blunt injuries (odds ratio 3.40,
95% confidence interval, 1.68-6.88) and patients with a Glasgow Coma Score of 8
or lower (odds ratio 4.33, 95% confidence interval, 2.10-8.95). No statistically
significant difference was identified among patients with penetrating injuries or
with a Glasgow Coma Score >8 (P value .90 and .39, respectively). CONCLUSION:
International comparisons of interhospital variation in risk-adjusted outcomes
following trauma can identify opportunities for quality improvement and have the
potential to measure the impact of any corrective strategy implemented.
PMID- 28688520
TI - Are shipwrecks a real hazard for the ecosystem in the Mediterranean Sea?
AB - The aim of the present study was to evaluate the hazard from shipwrecks on
communities by a holistic approach taking into account different effects on
biological communities. Multibeam and Remotely Operated Vehicles surveys recorded
ecological assessment of fish and benthic species on three shipwrecks flooded
during the Second World War on Maerl beds habitats in the strait of Sicily.
Pollution levels of a wide range of chemicals of ecotoxicological concern were
also measured in sediments and in fish species from different trophic levels.
Statistical analysis evidenced significant differences among pollutant levels
between both sediments and fish collected in shipwreck sites and controls.
Concerning fish, significant effects due to the vessel's cargo type and flooding
position are recorded. In spite of that, our results underline that shipwrecks
are also a hotspots of biodiversity and a habitat for preservation strategies in
marine ecosystems that need to be monitored.
PMID- 28688521
TI - Spatial assessment of radiocaesium in the largest lagoon in Fukushima after the
TEPCO Fukushima Dai-ichi Nuclear Power Station accident.
AB - Radionuclides deposited on land by global fallouts and nuclear power station
accidents spread over coastal environments through estuarine areas connecting
land to ocean. In this study, we monitored activity concentration of radiocaesium
in surface sediment and re-suspended particles in Matsukawa-ura lagoon, the
largest lagoon in Fukushima, after the TEPCO Fukushima Dai-ichi Nuclear Power
Station accident. Radiocaesium distribution in surface sediment varied
spatiotemporally and irregularly due to the effect of tidal waves. The effective
half-life was significantly shorter than physical half-life, suggesting some
system of radiocaesium discharge in the lagoon. Sediment trap observation
revealed re-suspended particles from sediment were transported to the ocean. For
these reasons, it is suggested that re-suspension of particles in the lagoon and
their transportation to the ocean by the seawater exchange process are important
processes of radiocaesium discharge. Moreover, our results show that seawater
exchange process contributes to the dispersion of radiocaesium in the ocean.
PMID- 28688522
TI - Porta hepatis debulking procedures as part of primary cytoreductive surgery for
advanced ovarian cancer.
PMID- 28688524
TI - Prenatal exposure to brain-specific anion transporter-1-specific monoclonal
antibodies impairs cognitive function in post-natal life.
AB - Subclinical hypothyroidism is caused by thyroid hormone deficit and can lead to
impairments in mood and cognition. In brain, supply with thyroxine (T4) is
mediated by thyroid hormone transporters including the brain-specific anion
transporter-1 (BSAT-1). In humans and rodents, BSAT-1 is expressed in brain
microvessels and astrocytes. In this study, we tested whether exposure in utero
with BSAT-1-specific monoclonal antibodies (MabBSAT) will affect the cognitive
function of the progeny. On gestation day 16th, females were intravenously
treated with MabBSAT, non-specific antibodies (control 1), and saline (control
2). 72h after injection, MabBSAT were still detectable in the rat brain while non
specific antibodies were found. Immunocytochemistry showed that MabBSAT can bind
to cultured primary cerebrovascular rat cells. At the age of 1month, the progeny
was subjected to the Y-maze test, novel object recognition test, passive
avoidance test, and Morris water maze, which revealed significant impairments in
the cognitive function in the MabBSAT-exposed progeny compared to both control
progeny groups. Therefore, prenatal exposure to MabBSAT blocks brain BSAT-1 and
limits T4 influx to the brain. This impairs the cognitive function in exposed
progeny in the post-natal life.
PMID- 28688526
TI - Perceptions of academic administrators of the effect of involvement in doctoral
programs on faculty members' research and work-life balance.
AB - BACKGROUND: Support for research strongly predicts doctoral program faculty
members' research productivity. Although academic administrators affect such
support, their views of faculty members' use of support are unknown. PURPOSE: We
examined academic administrators' perceptions of institutional support and their
perceptions of the effects of teaching doctoral students on faculty members'
scholarship productivity and work-life balance. METHODS: An online survey was
completed by a random sample of 180 deans/directors of schools of nursing and
doctoral programs directors. Data were analyzed with descriptive statistics, chi
square analysis, and analysis of variance. DISCUSSION: Deans and doctoral program
directors viewed the level of productivity of program faculty as high to
moderately high and unchanged since faculty started teaching doctoral students.
Deans perceived better administrative research supports, productivity, and work
life balance of doctoral program faculty than did program directors. CONCLUSION:
Findings indicate the need for greater administrative support for scholarship and
mentoring given the changes in the composition of doctoral program faculty.
PMID- 28688527
TI - [Severe cutaneous necrosis induced by methotrexate].
PMID- 28688525
TI - Heterogeneous FDG-guided dose-escalation for locally advanced NSCLC (the NARLAL2
trial): Design and early dosimetric results of a randomized, multi-centre phase
III study.
AB - BACKGROUND AND PURPOSE: Local recurrence is frequent in locally advanced NSCLC
and is primarily located in FDG-avid parts of tumour and lymph nodes. Aiming at
improving local control without increasing toxicity, we designed a multi-centre
phase-III trial delivering inhomogeneous dose-escalation driven by FDG-avid
volumes, while respecting normal tissue constraints and requiring no increase in
mean lung dose. Dose-escalation driven by FDG-avid volumes, delivering mean doses
of 95Gy (tumour) and 74Gy (lymph nodes), was pursued and compared to standard
66Gy/33F plans. MATERIAL AND METHODS: Dose plans for the first thirty patients
enroled were analysed. Standard and escalated plans were created for all
patients, blinded to randomization, and compared for each patient in terms of the
ability to escalate while protecting normal tissue. RESULTS: The median dose
escalation in FDG-avid areas was 93.9Gy (tumour) and 73.0Gy (lymph nodes).
Escalation drove the GTV and CTV to mean doses for the tumour of 87.5Gy (GTV-T)
and 81.3Gy (CTV-T) in median. No significant differences in mean dose to lung and
heart between standard and escalated were found, but small volumes of e.g. the
bronchi received doses between 66 and 74Gy due to escalation. CONCLUSIONS: FDG
driven inhomogeneous dose-escalation achieves large increment in tumour and lymph
node dose, while delivering similar doses to normal tissue as homogenous standard
plans.
PMID- 28688528
TI - [Another 'last word' on Rowell's syndrome].
PMID- 28688529
TI - Predictors of cross-clamp-induced intraoperative monitoring changes during
carotid endarterectomy using both electroencephalography and somatosensory evoked
potentials.
AB - OBJECTIVE: The efficacy of selective shunting during carotid endarterectomy (CEA)
using intraoperative monitoring (IOM) for detection of cerebral ischemia is well
established. There is mounting evidence that monitoring of both
electroencephalography (EEG) and somatosensory evoked potentials (SSEPs)
increases the sensitivity of cerebral ischemia detection. Predictors of cerebral
ischemia requiring selective shunt placement using IOM of both EEG and SSEPs have
not been previously identified. METHODS: Consecutive patients who underwent CEA
between January 1, 2000, and December 31, 2010, were retrospectively analyzed.
Primary end points were IOM changes at any time during the operation or IOM
changes with carotid cross-clamping. Risk factors assessed included demographics;
baseline comorbidities; severity of ipsilateral and contralateral disease;
symptomatic status; and use of statin, antiplatelet, and beta-blocker
medications. Univariate and multivariate logistic regression was used for
analysis. RESULTS: During the 11-year study period, a total of 758 patients
underwent 804 CEAs (mean age, 70.6 +/- 9.5 years; 59.8% male; 39.2% symptomatic)
using IOM of both SSEPs and EEG for selective shunting guidance. Postoperative
stroke rate was 1.37%; 27.1% of patients had significant SSEP or EEG changes, and
49.1% of these were clamp induced (within 5 minutes of cross-clamping). Of these
patients, 83.2% received a shunt (11.4% overall). The most common reason that a
shunt was not placed after cross-clamp-induced changes was that the changes
resolved with further blood pressure elevation (8 of 17 patients). Clamp-induced
IOM changes were predictive of postoperative stroke (odds ratio [OR], 5.5; P =
.005). Risk factors for clamp-induced IOM changes were contralateral carotid
occlusion (OR, 2.5; P = .01), symptomatic stenosis (OR, 1.8; P = .006), and
diabetes (OR, 1.6; P = .03), whereas there was a trend toward increased risk with
female sex (OR, 1.5; P = .08). Risk factors for any IOM change (clamp and
nonclamp induced) were symptomatic carotid stenosis (OR, 1.8; P < .001), use of
beta blockers (OR, 1.5; P = .03), and female sex (OR, 1.5; P = .02). CONCLUSIONS:
Whereas some patients can be expected to experience IOM changes by monitoring of
SSEPs and EEG, a much smaller percentage will receive a shunt. Contralateral
carotid occlusion, symptomatic stenosis, diabetes, and female sex increase the
risk of clamp-induced IOM changes and should be anticipated to need a shunt.
Patients receiving beta blockers are likely to experience IOM changes during the
operation that are not associated with clamping.
PMID- 28688530
TI - Japanese standard for clinical stabilometry assessment: Current status and future
directions.
AB - Stabilometry is a useful tool for examining patients with functional disorders of
the vestibular system. However, measurement techniques and devices vary by
country. Therefore, international standardization of stabilometry is mandatory to
validate the exchange of important findings. This was advocated at the 1983
Posturography Meeting in Kyoto but has not been adopted worldwide, and each
country has continued to use unique regional measurement methods. In Japan,
stabilometry has widespread application in medical practice in conjunction with
research into its applications. With a goal of international standardization, we
present details of stabilometry measurement methods and their application in
Japan, together with a brief history and potential future directions of
stabilometry.
PMID- 28688531
TI - Tricky Findings in Liver Transplant Imaging: A Review of Pitfalls With Solutions.
AB - Orthotopic liver transplantation is the preferred treatment for end-stage liver
disease. Imaging plays an important role in the follow-up of transplant
recipients by identifying a variety of complications. Posttransplant liver
imaging can be challenging with altered vascular and nonvascular postoperative
findings closely mimicking pathologies. A thorough knowledge of these common
imaging findings in a posttransplant liver is essential for the radiologist to
avoid erroneous diagnoses and unnecessary workup. We focus on such imaging
findings and provide tips to avoid misinterpretation.
PMID- 28688532
TI - Missed Case Feedback and Quality Assurance Conferences in Radiology Resident
Education: A Survey of United States Radiology Program Directors.
AB - RATIONALE AND OBJECTIVES: Diagnostic Radiology (DR) residents typically generate
preliminary reports for imaging examinations, but few publications discuss
feedback regarding missed or misinterpreted findings. Our goal was to determine
the practices of United States DR residencies with respect to missed case
feedback, including the role of Quality Assurance (QA) conferences. MATERIALS AND
METHODS: A 23-item survey containing multiple-choice questions and several free
text fields was created and hosted on SurveyMonkeyR. An invitation to complete
the survey was sent via email to all DR Program Directors (PDs) or
representatives. Responses were tabulated and analyzed using SurveyMonkeyR
analytic tools and Microsoft Excel. RESULTS: 188 PDs or representatives were
emailed, resulting in 45 survey responses. Common types of missed case feedback
included resident QA case conferences (81%), resident self review of cases (72%),
discussion during readout at the end of shift (70%), and faculty-resident
meetings (67%). A minority of programs reported using automated methods of
resident feedback, such as PACS integration or automated emails. Most resident QA
conferences were held monthly (64%). Typical formats of conferences included
informal discussion (43%), formal presentation (30%), or case conferences (30%).
The majority (78%) of respondents rated resident missed case feedback mechanisms
at their institution as at least "good". CONCLUSION: DR residencies use a variety
of mechanisms to provide feedback to residents regarding missed or misinterpreted
cases, including QA conferences. Although several possibilities for improvement
in feedback mechanisms were highlighted by survey responses, most respondents had
a favorable view of their program's feedback processes.
PMID- 28688533
TI - Pathobiology and Diagnosis of Multiple Myeloma.
AB - OBJECTIVE: To understand the role of the genetic changes and bone marrow
microenvironment on the development, progression, and staging of multiple myeloma
(MM). DATA SOURCES: Peer-reviewed articles and clinical guidelines. CONCLUSION:
The acquisition of genetic changes and the bone marrow microenvironment in which
myeloma cells develop both influence the pathogenic potential of these malignant
cells and is reflected in staging of the disease, risk of progression, and
predicted response to treatment. IMPLICATIONS FOR NURSING PRACTICE: Treatment of
multiple myeloma is largely dependent on risk factors in which specific genetic
alterations play a large role. Clinicians should be aware of these genetic
changes and how they may influence the individual treatment plan for each
patient.
PMID- 28688534
TI - Introduction.
PMID- 28688535
TI - Caballeronia mineralivorans sp. nov., isolated from oak-Scleroderma citrinum
mycorrhizosphere.
AB - Six bacterial strains were isolated from the oak-Scleroderma citrinum
ectomycorrhizosphere in acidic and nutrient-poor forest soil for their high
efficacy to weather minerals. Four of the six isolates, PML1(12)T and PML1(4),
PML1(14) and PML1(16), were further characterized extensively. They were Gram
negative, obligate aerobic, motile, non spore forming and rod-shaped. The major
fatty acids of strain PML1(12)T were cyclo-C17:0, cyclo-C19:0-omega8c, C16:0 and
C18:1-omega7c. The GC content of the DNA was 60.8%. The 16S rRNA and GyrB
analyses showed that the four PML strains formed a distinct phylogenetic lineage
within the genus Caballeronia, most closely related to Caballeronia udeis. This
result was confirmed by whole-genome phylogeny analyses done on strain PML1(12)T.
The results of digital DNA-DNA relatedness further supported the separation of
the new isolates from closely related species. Morphological, chemotaxonomic
properties were also consistent with the description of the genus Caballeronia.
It is therefore proposed that strains PML1(12)T and PML1(4), PML1(14) and
PML1(16) be recognized as a novel species, for which the name Caballeronia
mineralivorans sp. nov. is proposed. The type strain is PML1(12)T (=DSM 104028
and LMG 2991).
PMID- 28688536
TI - Fibroepithelial lesions; The WHO spectrum.
AB - Fibroepithelial lesions of the breast comprise a morphologically and biologically
heterogeneous group of biphasic tumors with epithelial and stromal components
that demonstrate widely variable clinical behavior. Fibroadenomas are common
benign tumors with a number of histologic variants, most of which pose no
diagnostic challenge. Cellular and juvenile fibroadenomas can have overlapping
features with phyllodes tumors and should be recognized. Phyllodes tumors
constitute a spectrum of lesions with varying clinical behavior and are graded as
benign, borderline or malignant based on a set of histologic features according
to recommendations by the World Health Organization (WHO). Recent developments
have significantly expanded our understanding of the pathogenesis of
fibroepithelial lesions, highlighting fibroadenomas as true neoplasms and
underscoring a commonality with phyllodes tumors in the form of recurrent MED12
exon 2 mutations. In addition, sequencing studies have elucidated pathways
associated with phyllodes tumor progression. Accurate diagnosis and grading of
phyllodes tumors are important for patient management and prognosis, as grade
broadly correlates with increasing local recurrence risk, and essentially only
malignant tumors metastasize. However, classification of fibroepithelial lesions
in many cases remains challenging on both core biopsy and excision specimens. A
commonly encountered problem at the benign end of the spectrum is the distinction
of benign phyllodes tumor from cellular fibroadenoma, which is largely due to the
subjective nature of histologic features used in diagnosis and histologic overlap
between lesions. Grading is further complicated by the requirement to integrate
multiple subjective and ill-defined parameters. On the opposite end of the
histologic spectrum, malignant phyllodes tumors must be distinguished from more
common metaplastic carcinomas and from primary or metastatic sarcomas, which can
be especially difficult in core biopsies. Immunohistochemistry can be useful in
the differential diagnosis but should be interpreted with attention to caveats.
This review provides an overview and update on the spectrum of fibroepithelial
lesions, with special emphasis on common problems and practical issues in
diagnosis.
PMID- 28688537
TI - Calculated ventilation and effort distribution as a measure of respiratory
disease and Heliox effectiveness.
AB - In spite of numerous clinical studies, there is no consensus on the benefit
Heliox mixtures can bring to asthmatic patients in terms of work of breathing and
ventilation distribution. In this article we use a 3D finite element mathematical
model of the lung to study the impact of asthma on effort and ventilation
distribution along with the effect of Heliox compared to air. Lung surface
displacement fields extracted from computed tomography medical images are used to
prescribe realistic boundary conditions to the model. Asthma is simulated by
imposing bronchoconstrictions to some airways of the tracheo-bronchial tree based
on statistical laws deduced from the literature. This study illuminates potential
mechanisms for patient responsiveness to Heliox when affected by obstructive
pulmonary diseases. Responsiveness appears to be function of the pathology
severity, as well as its distal position in the tracheo-bronchial tree and
geometrical position within the lung.
PMID- 28688538
TI - Biomechanical properties of murine TMJ articular disc and condyle cartilage via
AFM-nanoindentation.
AB - This study aims to quantify the biomechanical properties of murine
temporomandibular joint (TMJ) articular disc and condyle cartilage using AFM
nanoindentation. For skeletally mature, 3-month old mice, the surface of condyle
cartilage was found to be significantly stiffer (306+/-84kPa, mean+/-95% CI) than
those of the superior (85+/-23kPa) and inferior (45+/-12kPa) sides of the
articular disc. On the disc surface, significant heterogeneity was also detected
across multiple anatomical sites, with the posterior end being the stiffest and
central region being the softest. Using SEM, this study also found that the
surfaces of disc are composed of anteroposteriorly oriented collagen fibers,
which are sporadically covered by thinner random fibrils. Such fibrous nature
results in both an F-D3/2 indentation response, which is a typical Hertzian
response for soft continuum tissue under a spherical tip, and a linear F-D
response, which is typical for fibrous tissues, further signifying the high
degree of tissue heterogeneity. In comparison, the surface of condyle cartilage
is dominated by thinner, randomly oriented collagen fibrils, leading to Hertzian
dominated indentation responses. As the first biomechanical study of murine TMJ,
this work will provide a basis for future investigations of TMJ tissue
development and osteoarthritis in various murine TMJ models.
PMID- 28688539
TI - US regional and demographic differences in prescription opioid and heroin-related
overdose hospitalizations.
AB - BACKGROUND: US opioid overdose death rates have increased between 2000 and 2014.
While, the increase in prescription opioid use has been linked to the increase in
heroin use, there are reasons to view this relationship as a partial explanation
for the recent increase in heroin-related harms. This study documents the
differences in trends in prescription opioid overdose-related (POD) and heroin
overdose-related (HOD) hospitalizations. METHODS: Data come from the National
Inpatient Sample (NIS) for the years 2000 through 2014. POD and HOD
hospitalizations were abstracted from ICD-9 codes. Rates of POD and HOD by census
region and census division were constructed along with separate rates for age and
race. Regression analysis analyzing trends across region were estimated along
with graphs for documenting differences in POD and HOD rates. RESULTS: POD
hospitalization rates were highest in the South and lowest in the Northeast. HOD
hospitalization rates were highest in the Northeast region and grew the fastest
in the Midwest. There was statistically significant heterogeneity in HOD trends
but not POD trends across the four regions between 2000 and 2014. Between 2012
and 2014 POD rates decreased in eight of the nine census divisions, with only New
England showing an increase. HOD hospitalization rates increased in all nine
census divisions between 2012 and 2014. Both POD and HOD rates show different
demographic patterns across the nine census divisions. CONCLUSION: Comparing POD
and HOD hospitalization trends reveals significant disparities in geographic as
well as demographic distributions. These epidemics are evolving and the simple
opioid-to-heroin transition story is both supported and challenged by this paper.
The opioid pill, heroin and fentanyl crises are intertwined yet increasingly have
drivers and outcomes that support examining them as distinct. Addressing these
complex and interrelated epidemics will require innovative public health research
and interventions which need to consider local and regional contexts.
PMID- 28688540
TI - Management of the condyle following the resection of tumours of the mandible.
AB - The aim of this study was to assess the management of the condyle during the
restoration of mandibular defects following tumour resection. A total of 41
patients who underwent simultaneous tumour resection and reconstruction with
vascularized iliac myocutaneous flaps for mandibular defects, from September 2010
to October 2014, were included. These patients were divided into three groups:
group 1, condyle preserved; group 2, condyle sacrificed; group 3, condyle frozen.
Patients were followed up at 1, 3, 6, and 12 months for the evaluation of
appearance, occlusion, and speech. The TMJ disability index (DI) and
craniomandibular index (CMI) differed significantly according to the method of
management, as well as the position and morphology of the reconstructed condyle
(P<0.01); however, no statistically significant difference in mandible movement
was observed between the groups. The DI and CMI values were significantly lower
in group 1 patients compared to group 2 and group 3 patients. The results showed
that TMJ function in group 1 patients was superior to that in group 2 and group 3
patients, and that function in group 3 patients was better than that in group 2
patients. In conclusion, the condyle should be preserved when benign mandibular
lesions are situated near the condyle, as preservation has a positive effect on
TMJ function and mandible movement.
PMID- 28688541
TI - Minimizing the t1-noise when using an indirect 1H high-resolution detection of
unlabeled samples.
AB - The most utilized through-space correlation 1H-{X} methods with proton indirect
detection use two consecutive transfers, 1H -> X and then X -> 1H, with the
evolution time t1 in the middle. When the X isotope is not 100% naturally
abundant (NA), only the signal of the protons close to these isotopes is
modulated by the 1H-X dipolar interactions. This signal is theoretically
disentangled with phase-cycling from the un-modulated one. However, this
separation is never perfect and it may lead to t1-noise in case of isotopes with
very small NA, such as 13C or even worse 15N. One way to reduce this t1-noise is
to minimize, 'purge', during t1 the un-modulated 1H magnetization before trying
to suppress it with phase-cycling. We analyze experimentally several sequences
following the HORROR condition, which allow purging the 1H transverse
magnetization. The comparison is made at three spinning speeds, including very
fast ones for 1H resolution: 27.75, 55.5 and 111 kHz. We show (i) that the
efficiency of this purging process increases with the spinning speed, and (ii)
that the best recoupling sequences are the two simplest ones: XY and S1 = SR212.
We then compare the S/N that can be achieved with the two most used 1H-{X} 2D
methods, called D-HMQC and CP-CP. The only difference in between these two
methods is that the transfers are done with either two pi/2-pulses on X channel
(D-HMQC), or two Cross-Polarization (CP) transfers (CP-CP). The first method, D
HMQC, is very robust and should be preferred when indirectly detecting nuclei
with high NA. The second method, CP-CP, (i) requires experimental precautions to
limit the t1-noise, and (ii) is difficult to use with quadrupolar nuclei because
the two CP transfers are then not efficient nor robust. However, CP-CP is
presently the best method to indirectly detect isotopes with small NA, such as
13C and 15N.
PMID- 28688523
TI - Erratum to "Worldwide comparison of ovarian cancer survival: Histological group
and stage at diagnosis (CONCORD-2)" [Gynecol. Oncol. 144 (2017) 396-404].
PMID- 28688542
TI - Evaluation of apoptotic activity of Withania coagulans methanolic extract against
human breast cancer and Vero cell lines.
AB - BACKGROUND: The genus Withania (Family: Solanaceae) holds an important position
in Ayurveda, the Indian traditional system of medicine. Withania somnifera Dunal
and Withania coagulans Dunal have been documented in folklore as panaceas for
various ailments since time immemorial. W. coagulans (WC), commonly called as
Indian cheese maker is used for fermenting milk for cheese production in various
parts of India. OBJECTIVES: In the study, in vitro cytotoxicity of methanolic
extract of dried fruits (berries) of WC was evaluated in a dose dependent manner
using trypan blue dye exclusion method against human breast cancer cell line MDA
MB-231 and normal kidney epithelial cell line Vero in the range 20-200 MUg/ml.
MATERIAL AND METHODS: The percentage viability of the cell lines was determined
by using MTT assay and cytometry. RESULTS: Methanolic extract of WC showed
significant anticancer activity against MDA-MB-231 cell line. Cell viability was
reduced to about 50% at 40 MUg/ml of methanolic extract in 50% DMSO. Cytotoxicity
of the extract was lower in 10% and 1% DMSO. On the other hand, methanolic
extract of WC did not exhibit any significant in vitro activity against Vero
cells at 170 and 200 MUg/ml. AGE of isolated DNA from treated cancer cells
revealed characteristic ladder like fragmentation, a hallmark of apoptosis. HPLC
profiling was carried out for identification of the active components, which
demonstrated the presence of Withaferin A in the methanolic extract. CONCLUSION:
Methanolic extract of WC possesses apoptotic activity against human breast cancer
cells in vitro albeit lower in comparison to W. somnifera and warrants further
investigation.
PMID- 28688543
TI - Liver steatosis: The new epidemic of the Third Millennium. Benign liver state or
silent killer?
AB - Until the end of the 90's of the last century, rather little attention was paid
to the issue of the non-alcoholic fatty liver disease (NAFLD), perhaps due to the
fact that the newly discovered hepatitis C virus did attract a paramount interest
of hepatologists and researchers. On the other side, fatty liver was considered a
relatively uncommon cause of liver damage, occurring almost exclusively in obese
females, often associated with non-insulin dependent diabetes mellitus (NIDDM),
and with a relatively benign prognosis. Due to the complexity of international
available guidelines, we decide to approach the main unsolved issues on this
topic in the form of a dialog between a hepatologist and a man suffering from
NAFLD, trying to give evidence-based answers to the more frequently asked
questions from patients and their GPs. This is the third instalment of the
Trilogy of Dr. Calm, a skilled hepatologist who will try to clearly explain to
his patient Mr. Frightened the natural history of NAFLD, the diagnostic workup,
indications for liver biopsy and suggested medical treatments, advicing him on
the importance of dietary intervention and lifestyle modifications.
PMID- 28688544
TI - The ominous skin nodules.
PMID- 28688545
TI - A focus on the state of the art of food waste/losses issue and suggestions for
future researches.
AB - Today, the role of the supply chain (SC) strategies in Food-Waste/Losses (F-W/L)
generation is neglected, because F-W/L are generally considered an unavoidable
consequence of accidental events. Therefore, only operating plans are today put
into practice, which aim at reducing the impact of product losses along the SC.
This involves that structured analyses and strategic SC approaches are not
available for the prevention/minimization of F-W/L. The paper aims at changing
the perspective, and promoting the hypothesis that generation of F-W/L mainly
depends on the SC strategies put into practice that are usually optimized on the
basis of the market demand. The paper considers the F-W/L an intrinsic
characteristic of the SC, which must be put in relation with the market demand
and the shelf life of products, for given boundary conditions (legal constraints,
politic decisions, climatic and micro macro-economic factors). Thus, the paper
aims at reviewing the state of the art of the F-W/L issue, and proposing new
research topics in the field of the prevention and minimization of F-W/L, by
focusing on: (i) the forecasting of F-W/L, the implementation of adaptive
holistic approaches that model the non-stationary and holistic behaviour of the
phenomenon; (ii) the determination of analytical conditions that entail the
generation of F-W/L, in relation to the implementation of specific SC strategies;
(iii) the study of mathematical models for the assessment of the shelf life, and
the evaluation of innovative technologies, which enable the shelf life
monitoring; (iv) the study of new shelf life-dependent demand models based on the
consumer-utility theory; (v) the redesign of the logistic SC management models,
by proposing new SC coordination models, planning and replenishment strategies,
and pricing models, for the prevention/minimization of the predictable component
of F-W/L; (vi) the design of new risk assessment plans for the management of the
accidental component of F-W/L.
PMID- 28688546
TI - Mechanical pretreatment of waste paper for biogas production.
AB - In the anaerobic digestion of lignocellulosic materials such as waste paper, the
accessibility of microorganisms to the fermentable sugars is restricted by their
complex structure. A mechanical pretreatment with a Hollander beater was assessed
in order to reduce the biomass particle size and to increase the feedstock'
specific surface area available to the microorganisms, and therefore improve the
biogas yield. Pretreatment of paper waste for 60min improves the methane yield by
21%, from a value of 210ml/gVS corresponding to untreated paper waste to
254ml/gVS. 30min pretreatment have no significant effect on the methane yield. A
response surface methodology was used to evaluate the effect of the beating time
and feedstock/inoculum ratio on the methane yield. An optimum methane yield of
253ml/gVS was achieved at 55min of beating pretreatment and a F/I ratio of 0.3.
PMID- 28688547
TI - Preventive recommendations on the use of valproic acid in pregnant or gestational
women to be very present.
PMID- 28688548
TI - EEG activity as an objective measure of cognitive load during effortful
listening: A study on pediatric subjects with bilateral, asymmetric sensorineural
hearing loss.
AB - OBJECTIVES: Deaf subjects with hearing aids or cochlear implants generally find
it challenging to understand speech in noisy environments where a great deal of
listening effort and cognitive load are invested. In prelingually deaf children,
such difficulties may have detrimental consequences on the learning process and,
later in life, on academic performance. Despite the importance of such a topic,
currently, there is no validated test for the assessment of cognitive load during
audiological tasks. Recently, alpha and theta EEG rhythm variations in the
parietal and frontal areas, respectively, have been used as indicators of
cognitive load in adult subjects. The aim of the present study was to
investigate, by means of EEG, the cognitive load of pediatric subjects affected
by asymmetric sensorineural hearing loss as they were engaged in a speech-in
noise identification task. METHODS: Seven children (4F and 3M, age range = 8-16
years) affected by asymmetric sensorineural hearing loss (i.e. profound degree on
one side, mild-to-severe degree on the other side) and using a hearing aid only
in their better ear, were included in the study. All of them underwent EEG
recording during a speech-in-noise identification task: the experimental
conditions were quiet, binaural noise, noise to the better hearing ear and noise
to the poorer hearing ear. The subjects' Speech Recognition Thresholds (SRT) were
also measured in each test condition. The primary outcome measures were: frontal
EEG Power Spectral Density (PSD) in the theta band and parietal EEG PSD in the
alpha band, as assessed before stimulus (word) onset. RESULTS: No statistically
significant differences were noted among frontal theta power levels in the four
test conditions. However, parietal alpha power levels were significantly higher
in the "binaural noise" and in the "noise to worse hearing ear" conditions than
in the "quiet" and "noise to better hearing ear" conditions (p < 0.001). SRT
scores were consistent with task difficulty, but did not correlate with alpha and
theta power level variations. CONCLUSION: This is the first time that EEG has
been applied to children with sensorineural hearing loss with the purpose of
studying the cognitive load during effortful listening. Significantly higher
parietal alpha power levels in two of three noisy conditions, compared to the
quiet condition, are consistent with increased cognitive load. Specifically,
considering the time window of the analysis (pre-stimulus), parietal alpha power
levels may be a measure of cognitive functions such as sustained attention and
selective inhibition. In this respect, the significantly lower parietal alpha
power levels in the most challenging listening condition (i.e. noise to the
better ear) may be attributed to loss of attention and to the subsequent fatigue
and "withdrawal" from the task at hand.
PMID- 28688549
TI - Curcumin protects against acoustic trauma in the rat cochlea.
AB - OBJECTIVES: In this study we evaluated the therapeutic utility of curcumin in a
rodent model of acoustic trauma using histopathology, immunohistochemical, and
distortion product otoacoustic emission (DPOAEs) measurements. METHODS: 28 Wistar
albino rats were included in the study and randomly assigned to 4 treatment
groups. The first group (group 1) served as the control and was exposed to
acoustic trauma alone. Group 2 was the curcumin group. Group 3 was the curcumin
plus acoustic trauma group. Group 4 was the saline plus acoustic trauma group.
Otoacoustic emission measurements were collected at the end of the experiment and
all animals were sacrificed. Cochlea were collected and prepared for TUNEL (TdT
mediated deoxyuridinetriphosphate nick end-labelling) staining assay. RESULTS:
Group 3 maintained baseline DPOAEs values at 3000 Hz, 4000 Hz and 8000 Hz on the
3rd and 5th day of the experiment. DPOAEs results were correlated with the
immunohistochemical and histopathological findings in all groups. In comparison
to the histopathologic control group, Group 1 exhibited a statistically
significant increase in apoptotic indices in the organ of Corti, inner hair cell,
and outer hair cell areas (p < 0.05). Relative to the control group, rats in
Group 3 showed little increase in inner hair cell and outer hair cell apoptotic
indices. CONCLUSIONS: Our results support the conclusion that curcumin may
protect the cochlear tissues from acoustic trauma in rats. Curcumin injection
prior to or after an acoustic trauma reduces cochlear hair cell damage and may
protect against hearing loss.
PMID- 28688550
TI - A quality study of family-centered care coordination to improve care for children
undergoing tracheostomy and the quality of life for their caregivers.
AB - IMPORTANCE: Approximately 4000 U.S. children undergo tracheostomy yearly [1], and
these surgeries often result in hospital re-admissions that have definite cost
and caregiver burdens due to complications that are avoidable with proper
training and support. OBJECTIVE: To assess the impact of a Family-Centered Care
Coordination (FCCC) program on the quality of care received by children
undergoing tracheostomy and their caregivers. DESIGN: Caregivers of children
undergoing tracheostomies from January 2012 to January 2013 and then a different
set of caregivers of children undergoing tracheostomies from January 2015 to
January 2016 completed both the Pediatric Tracheostomy Health Status Instrument
(PTHSI) 1 month after discharge and the Medical Complications Associated with
Pediatric Tracheostomy (MCAT) questionnaire 6 months after initial tracheostomy.
To assess complication rates, these same sets of caregivers were asked to
complete the MCAT and only those who provided complete medical data for all 6
months were included for comparative analysis. SETTING: The PTHSI and MCAT were
administered at Massachusetts Eye and Ear in a hospital setting. PARTICIPANTS:
Ten caregivers of children undergoing tracheostomies completed the PTHSI before
FCCC program implementation and12 caregivers then completed the PTHSI after FCCC
implementation. For each of the 2 groups, 5 caregivers provided complete data on
the MCAT questionnaires. EXPOSURES: FCCC is a collection of programs, policies,
and tools designed to ensure safe transition home for children undergoing
tracheostomies, reduce re-admission rates, and minimize "caregiver burden". MAIN
OUTCOMES AND MEASURES: The PTHSI is a validated caregiver quality of life
instrument that was supplemented by the MCAT which records post-discharge medical
issues following tracheostomy that relate specifically to the tracheotomy
placement. RESULTS: The time to first follow-up appointment decreased from 6.4
weeks (SD = 1.52) to 6 days (SD = 0.18) with FCCC implementation. The total MCAT
scores decreased from 15.2 (SD = 1.1) to 1.3 (SD = 1.3) (Wilcoxon sum rank test:
P < 0.016) whereas neither PTHSI scores (P = 0.32) nor the specific caregiver
burden domain (P = 0.18) demonstrated a significant change. CONCLUSIONS: and
Relevance: By reducing the time to first follow-up after tracheostomy and by
optimizing caregiver tracheostomy tube care and teaching, children's quality of
care and caregiver burden can be significantly improved.
PMID- 28688551
TI - Pediatric invasive fungal rhinosinusitis: An investigation of 17 patients.
AB - PURPOSE: To investigate outcomes of pediatric patients at a single institution
with invasive fungal rhinosinusitis (IFRS) and to determine variables that impact
overall survival. METHODS: All pediatric patients at a large tertiary children's
hospital diagnosed with IFRS confirmed by surgical pathology from 2009 to 2015
were retrospectively reviewed. Demographics, underlying diseases, symptoms,
antifungal therapy, absolute neutrophil count (ANC), surgical management,and
outcomes were analyzed. RESULTS: Seventeen patients were identified with IFRS
with an average age of 8.7 years and 53% male. Hematologic malignancy was the
most common (n = 13) underlying disease. The most common presenting symptoms were
fever (82%) and congestion (41%). 15 patients had severe neutropenia (Absolute
Neutrophil Count (ANC) < 500) within 2 weeks prior to diagnosis. The average ANC
at time of diagnosis was 1420 cells/uL. 16 patients were treated with serial
nasal endoscopy and debridement, while 1 patient was treated with an open
approach. 16 received combination antifungals while 1 was treated with
amphotericin monotherapy. The most common genus cultured was Fusarium (n = 6).
The average number of surgical interventions was 3.4, with the average interval
between interventions 6.2 days. 13 of 17 (76%) were cleared of IFRS. Overall
survival at 6 months was 41%. CONCLUSION: Pediatric IFRS is a life-threatening
disease that requires a coordinated surgical and medical approach. Despite a
relatively high local control rate, overall mortality remains disappointingly
high, reflecting the disease's underlying pathogenesis - lack of host defense and
risk of disseminated fungal infection. Further investigation is necessary to
reveal optimal management with regards to antifungal therapy, surgery, and
utility of labs.
PMID- 28688552
TI - Hearing aids for otitis media with effusion: Do children use them?
AB - INTRODUCTION: ENT surgeons may refer children with otitis media with effusion
(OME) to audiology for consideration of hearing aids. They are an option for the
treatment of OME, but are only effective if the child actually wears them. Our
study investigated what proportion of children referred for hearing aids actually
receive them, and whether children use them. METHOD: Retrospective study of
children referred to audiology from November 2013 to August 2014, including 70
children referred by ENT for hearing aids for OME, plus a further 5 children with
OME given hearing aids through direct access audiology service. RESULTS: During
the study period, there were 202 referrals of children to audiology, of which 70
(34.7%) were for consideration of hearing aids for OME. Of these 70 referred
children, 37 (52.9%) were not fitted with hearing aids due to normal audiometry
(23), asymptomatic mild hearing loss (7), nonattendance (3), clinical decision to
just monitor hearing (1), parental decline (2), and unrecorded reason (1). A
total of 38 children (including direct access patients) were fitted with hearing
aids for OME. Majority (36/38) of children issued aids used them, 16 all day, 7
only at school, 1 only at home, 3 only when needed, and 9 used them for an
unspecified duration; 1 child's use of hearing aids was unrecorded, and 1 child
refused to use it. 21 were fitted bilaterally and 17 unilaterally. 37 were behind
the ear aids and 1 a BAHA softband. CONCLUSIONS: A third of referrals to
paediatric audiology by ENT are for consideration of hearing aids for OME. Only
about half of children referred to audiology for hearing aids for OME actually
receive them, as by the time they see audiology the hearing loss has frequently
resolved or is asymptomatic so that aiding is unwarranted. Once fitted, they
appear to be well accepted. Hearing aids have fair utilization in children fitted
with them for OME.
PMID- 28688553
TI - Clinical role of electrocochleography in children with auditory neuropathy
spectrum disorder.
AB - OBJECTIVES: To assess electrocochleography (ECochG) to tones as an instrument to
account for CI speech perception outcomes in children with auditory neuropathy
spectrum disorder (ANSD). MATERIALS & METHODS: Children (<18 years) receiving CIs
for ANSD (n = 30) and non-ANSD (n = 74) etiologies of hearing loss were evaluated
with ECochG using tone bursts (0.25-4 kHz). The total response (TR) is the sum of
spectral peaks of responses across frequencies. The compound action potential
(CAP) and the auditory nerve neurophonic (ANN) in ECochG waveforms were used to
estimate nerve activity and calculate nerve score. Performance on open-set
monosyllabic word tests was the outcome measure. Standard statistical methods
were applied. RESULTS: On average, TR was larger in ANSD than in non-ANSD
subjects. Most ANSD (73.3%) and non-ANSD (87.8%) subjects achieved open-set
speech perception; TR accounted for 33% and 20% of variability in the outcomes,
respectively. In the ANSD group, the PTA accounted for 69.3% of the variability,
but there was no relationship with outcomes in the non-ANSD group. In both
populations, nerve score was sensitive in identifying subjects at risk for not
acquiring open-set speech perception, while the CAP and the ANN were more
specific. CONCLUSION: In both subject groups, the TRs correlated with outcomes
but these measures were notably larger in the ANSD group. There was also strong
correlation between PTA and speech perception outcome in ANSD group. In both
subject populations, weaker evidence of neural activity was related to failure to
achieve open-set speech perception.
PMID- 28688554
TI - Acute pediatric neck infections: Outcomes in a seven-year series.
AB - OBJECTIVES: The aim of this study was to analyse the epidemiology, clinical
presentation, diagnostic clues, as biochemical parameters and imaging studies, of
children with acute neck infections (ANI) to identify possible independent
prognostic factors leading to complications and prolonged hospitalization.
METHODS: Records of children admitted to a tertiary university hospital from
January 2008 to December 2014 with a diagnosis of ANIs were reviewed
retrospectively. Diseases were categorized according to the site of infection and
patients were divided into two groups: children (aged<10 years) and adolescents
(aged 10-18 years). RESULTS: A total of 102 patients belonged to the children's
group and 57 were adolescents. Forty-nine patients (27.2%) received antibiotics
prior to presentation. The most frequent ANI was peritonsillar abscess (n = 72).
Four peritonsillar abscesses progressed to parapharyngeal and retropharyngeal
abscesses (n = 2 respectively). An association between age and type of abscess
was found, with most of the retropharyngeal abscesses occurring in children (p =
0.05), and the submandibular abscesses in adolescents (p < 0.001). The most
frequent symptoms/signs were fever (63.9%) and odynophagia (50.6%). Upon
admission, all patients received intravenous antibiotics and 86.8% underwent
drainage of the abscess. Cultures were harvested in 87 abscesses and the most
frequent pathogen isolated was Streptococcus pyogenes. Signs of airway
obstruction occurred in two patients with submandibular abscess, one with
peritonsillar and one with parapharyngeal abscess. There were no cases of death
or severe sequelae. Recurrent ANIs were observed in eight patients including two
infected branchial cysts. Children, presence of multiple abscesses and palpable
cervical mass on admission, absence of odynophagia and pharyngeal bulging,
surgery with general anaesthesia and surgery after 24 h, were associated with
prolonged hospitalization. Presence of toothache and neck pain on admission were
identified as predictors of complications. CONCLUSIONS: The present study found,
that often, the diagnosis and treatment of neck abscesses in paediatric patients
is not straightforward, but can achieve a favourable outcome. The primary
location of the ANI appears to vary in different paediatric age groups. Younger
age, presence of multiple abscesses or a palpable cervical mass on admission,
were associated with prolonged hospitalization. Presence of toothache and neck
pain on admission was identified as possible predictors of complications.
PMID- 28688555
TI - Airway stenting in a child with spondyloepiphyseal dysplasia congenita: 13-Year
survival.
AB - We describe the case of a boy with spondyloepiphyseal dysplasia congenita. At
birth, he experienced severe respiratory distress necessitating tracheotomy.
Endoscopy done because mechanical ventilation failed to resolve desaturations
disclosed severe tracheo-bronchomalacia. A Polyflex silicone stent was placed in
the trachea (replaced by Y-Dumon stent) and 2 Palmaz metallic stents in the
mainstem bronchi (overlapped with 2 Jomed stents 5 years later). Airway stenting
guaranteed a suitable respiratory status and allowed a child who was expected to
die at birth, to reach 13.5 years old in good conditions.
PMID- 28688556
TI - Pediatric Langerhans cell histiocytosis of the lateral skull base.
AB - OBJECTIVE: Describe the presentation, imaging characteristics, management, and
outcomes of pediatric patients with Langerhans cell histiocytosis (LCH) of the
temporal bone. METHODS: A retrospective chart review was performed between 2000
and 2014 at a single tertiary care children's hospital. Fourteen patients were
identified with a diagnosis of LCH and involvement of the temporal bone. RESULTS:
Ten patients were female and ten were Caucasian. Mean age at diagnosis was 3
years (range 0.3-9.6 years). The most common presenting symptoms were scalp
lesions, postauricular lesions, otalgia, and persistent ear infections. Three
patients had documented hearing loss. Four cases had otic capsule invasion.
Computed tomography demonstrated a lytic temporal bone lesion within the
following subsites: mastoid, squamous temporal bone, external auditory canal,
middle ear, and petrous apex. Four patients had intracranial disease. Extent and
location of disease prompted all patients to be initially managed with
chemotherapy. Surgical excision was limited to one case of localized recurrence.
After a mean follow-up of 85.2 months (SD 42.4 months) there were no deaths but
eight patients had a recurrence. Two patients developed long-term otologic
sequelae requiring surgery. One patient developed labyrinthitis ossificans.
CONCLUSION: LCH has a varied presentation, age distribution, and treatment
algorithm. This series of 14 pediatric patients with temporal bone involvement
supports a limited role for surgical resection. Long-term follow-up is critical
for detection of local and disseminated disease, and for monitoring of otologic
complications.
PMID- 28688557
TI - The outcomes of endoscopic management in young children with subglottic stenosis.
AB - : Subglottic stenosis (SGS) is a common cause of obstructed airway in children,
and the treatment of pediatric SGS, especially congenital SGS, remains a
challenge for the otolaryngologist. OBJECTIVE: To analyze the outcomes of
endoscopic management in young children with SGS. METHODS: We performed a
retrospective review of treatment with endoscopic balloon dilation (EBD) or EBD
combined with endoscopic anterior cricoid split (EACS) for young SGS children,
from December 2008 to December 2015. The ages of patients ranged from 2 days to
12 years, median age was 5 months. The grade of them ranged from II to IV.
RESULTS: For acute acquired SGS, 19 cases received EBD alone and the other 3
cases received EBD and EACS, the success rate was about 95.5%; For chronic
acquired SGS, EBD and EACS was performed in 6 patients with a success rate of
66.7%; For congenital SGS, EBD and EACS was performed in 28 patients with a
success rate of 85.7%. Overall, the success rate of endoscopic management in 56
young children was about 87.5%. Besides, No procedure-related complications were
observed in any patients. CONCLUSIONS: Endoscopic surgical technique offers a
safe and effective approach for treatment of young children with SGS, especially
in congenital SGS.
PMID- 28688558
TI - Bilateral congenital cholesteatoma: Surgical treatment and considerations.
AB - OBJECTIVES: To describe a multicenter study regarding surgical management of
bilateral congenital cholesteatoma (BCC) and underline the importance of
endoscopes in the management of this condition. In BCC, hearing preservation is
more crucial than in unilateral cases. The endoscopic approach allows complete
removal of cholesteatoma via a minimally invasive technique offering low residual
disease rates while preserving the normal physiology of the middle ear and
possibly the ossicular chain. STUDY DESIGN: Retrospective chart and surgical
video review of patients with BCC who underwent surgery at Otolaryngology
Department of Modena and Verona University Hospitals and the Hospital for Sick
Children, Toronto. METHODS: From 2002 to November 2016, six patients were
identified with bilateral congenital cholesteatoma and included in this study.
Pre-operative assessments, surgical treatments and outcomes were collected and
described. RESULTS: The median age at presentation was 4 years (range 2-7 years).
A microscopic post auricular tympanoplasty was performed in two ears, four
underwent a canal wall up mastoidectomy procedure and in the other six a
transcanal endoscopic approach (TEA) was used. No intra- or post-operative
complications were observed in any patients. The mean follow up period was 54.5
months. CONCLUSIONS: When both ears are involved with congenital cholesteatoma,
it is particularly important to use a minimally invasive technique that preserves
normal ossicular and mastoid structure and function whenever possible. In many
cases this can be achieved with TEA, even in young children. In addition the
endoscope allows good surgical control of cholesteatoma removal from hidden
recesses.
PMID- 28688559
TI - An evaluation of oxidative and nitrosative stress in children-who-stutter and its
relationship to severity.
AB - OBJECTIVES: Although there has been much research into the cause of stuttering,
it has not yet been fully clarified. There is known to be a close relationship
between stress severity and stuttering. The aim of this study was to evaluate the
levels of oxidative and nitrosative stress by comparing a stuttering group and a
control group. It was also aimed to evaluate the relationship between the
oxidative and nitrosative stress levels and the severity of the stutter. METHODS:
The study included a total of 80 individuals, comprising a study group of 40 and
a control group of 40. The severity of the stutter in the patient group was
evaluated with the Stuttering Severity Instrument 3 (SSI). Blood samples were
taken from both the patient and control groups and malondialdehyde (MDA), 3
nitrotyrosine (3-NT), nitric oxide (NO), catalase (CAT), and superoxide dismutase
(SOD) concentrations were examined. RESULTS: In the stuttering patients, MDA, 3
NT, NO, CAT, and SOD activity were determined to be statistically significantly
higher than those of the control group (all p:0.001). In the ROC analysis, there
was good diagnostic value for NO, with the area under the curve as 1.0. A direct,
positive, statistically significant correlation was determined between SSI points
and MDA values (r = 0.317, p = 0.046). CONCLUSION: The results of the study
showed that the oxidative and nitrosative stress levels of the stuttering
patients were higher than those of the control group. With 100% sensitivity and
specificity, it is thought that NO in particular could be important for the
diagnosis and treatment of these patients. As the severity of the stutter
increased, so there was an increase in MDA, suggesting that MDA is important in
stuttering.
PMID- 28688560
TI - Speech-evoked auditory brainstem responses in children with hearing loss.
AB - OBJECTIVE: The main objective of the present study was to investigate subcortical
auditory processing in children with sensorineural hearing loss. METHODS:
Auditory Brainstem Responses (ABRs) were recorded using click and
speech/da/stimuli. Twenty-five children, aged 6-14 years old, participated in the
study: 13 with normal hearing acuity and 12 with sensorineural hearing loss.
RESULTS: No significant differences were observed for the click-evoked ABRs
between normal hearing and hearing-impaired groups. For the speech-evoked ABRs,
no significant differences were found for the latencies of the following
responses between the two groups: onset (V and A), transition (C), one of the
steady-state wave (F), and offset (O). However, the latency of the steady-state
waves (D and E) was significantly longer for the hearing-impaired compared to the
normal hearing group. Furthermore, the amplitude of the offset wave O and of the
envelope frequency response (EFR) of the speech-evoked ABRs was significantly
larger for the hearing-impaired compared to the normal hearing group.
CONCLUSIONS: Results obtained from the speech-evoked ABRs suggest that children
with a mild to moderately-severe sensorineural hearing loss have a specific
pattern of subcortical auditory processing. Our results show differences for the
speech-evoked ABRs in normal hearing children compared to hearing-impaired
children. These results add to the body of the literature on how children with
hearing loss process speech at the brainstem level.
PMID- 28688561
TI - Uncovering the pathogenesis of microtia using bioinformatics approach.
AB - OBJECTIVE: Bioinformatics is widely used in the field of cancer research, but in
the research of pathogenesis of congenital malformations the situation is
different. The aim of this study was to explore the underlying mechanism using
bioinformatics approach. METHODS: The data were available from Mouse Genome
Informatics and Pubmed. Protein-protein interaction (PPI) network of pathogenic
genes was conducted using STRING. Gene ontology and pathway enrichment analyses
were also performed to pathogenic genes. RESULTS: Total 63 genes were identified
as pathogenic genes in the study. The PPI networks for pathogenic genes were
constructed, which contained 62 nodes and 228 edges with PAX6, FGFR1 and CTNNB1
as the hub genes. All the genes were linked to 921 pathways in biological
processes, 31 pathways in cell component, 41 pathways in molecular function, and
76 pathways in the KEGG. These genes were discovered significantly enriched in
embryonic organ development, ear morphogenesis, ear development, and regulation
of RNA synthesis and processing. CONCLUSIONS: bioinformatics methods were
utilized to analysis pathogenic genes involved in microtia development, including
pathogenic genes identifying, PPI network construction and functional analysis.
And we also predicted that several potential mechanisms might contribute to
occurrence of microtia by disturbing GO terms and pathways. This approach could
be useful for the study of the etiology and pathogenesis of microtia.
PMID- 28688562
TI - Decisional regret following ventilation tube insertion.
AB - OBJECTIVE: The purpose of this study was to see if parental regret following
ventilation tube (VT) insertion was related to non-resolution of ear infections
and thus ongoing need for otolaryngological care and VT reinsertion. MATERIALS
AND METHODS: All consecutive parents presenting with children who had VT in place
were given a validated regret survey and asked the reason for their visit. Chart
review was used for medical history. RESULTS: Two hundred and ten respondents
were included. The children involved had a mean age of 5.2 years, 63.3% were
male, and mean number of years since first VT insertion was 1.12 with a range of
0.04-9.28 years. 70.5% had a regret score of 0, with mean score 6.98 (95%CI 5.11
8.85). Scores were significantly higher for parents who presented their child
with an ear complaint such as otorrhea (15.52, 95%CI 7.67-23.37, p = 0.004).
Parents whose children had a history of reflux had significantly lower regret
scores than parents whose children did not have a history of reflux (3.33 versus
7.89, p = 0.007). Parental regret was unrelated to patient age, other
comorbidities, indication for initial tube insertion, hearing status on the day
of inquiry, number of sets of tubes, visits for otorrhea, prescriptions given for
eardrops, clinic visits, or length of follow-up. CONCLUSION: Transient factors
may influence decisional regret at any given time. For parents whose children
receive VT, regret is not related to prolonged specialized ear care and need for
VT reinsertion.
PMID- 28688563
TI - A novel mutation in the MYO7A gene is associated with Usher syndrome type 1 in a
Chinese family.
AB - OBJECTIVES: We aimed to investigate the genetic causes of hearing loss in a
Chinese proband with autosomal recessive congenital deafness. METHODS: The
targeted capture of 159 known deafness genes and next-generation sequencing were
performed to study the genetic causes of hearing loss in the Chinese family.
Sanger sequencing was employed to verify the variant mutations in members of this
family. RESULTS: The proband harbored two mutations in the MYO7A gene in the form
of compound heterozygosity. She was found to be heterozygous for a novel
insertion mutation c.3847_3848 ins TCTG (p.N1285LfsX24) in exon 30 and for the
known mutation c.2239_2240delAG (p.R747S fsX16)in exon 19. The novel mutation was
absent in the 1000 Genomes Project. These variants were carried in the
heterozygous state by the parents and were therefore co-segregated with the
genetic disease. Clinical re-assessment, including detailed audiologic and ocular
examinations, revealed congenital deafness and retinitis pigmentosa in the
proband. Collectively, the combination of audiometric, ophthalmologic and genetic
examinations successfully confirmed the phenotype of Usher syndrome type 1
(USH1). CONCLUSION: This study demonstrates that the novel mutation
c.3847_3848insTCTG (p. N1285LfsX24) in compound heterozygosity with
c.2239_2240delAG in the MYO7A gene is the main cause of USH1 in the proband. Our
study expands the mutational spectrum of MYO7A and provides a foundation for
further investigations elucidating the MYO7A-related mechanisms of USH1.
PMID- 28688564
TI - Utility of intraoperative and postoperative radiographs in pediatric cochlear
implant surgery.
AB - OBJECTIVE: Routine plain film radiographs are often obtained to confirm proper
placement of electrode after pediatric cochlear implant surgery. Objective is to
evaluate necessity of routine radiographs in pediatric cochlear implant cases.
STUDY DESIGN: Retrospective review. SETTING: Two tertiary care academic centers.
SUBJECTS AND METHODS: Review of all children that underwent cochlear implantation
from January 2003 thru June 2015. Exclusions include patients without
intraoperative evoked compound action potential (ECAP) data or radiographs and
patients undergoing revision surgeries. RESULTS: 235 pediatric patients underwent
371 cochlear implants. ECAP measurements were not available in two cases and were
excluded from study. Radiographs were obtained in 35/369 cases due to
intraoperative concern and four had abnormal findings. All four cases underwent
change in management. One other patient had an x-ray because of difficult
insertion and abnormal ECAP. Radiograph was normal; however, incision was opened
and electrodes inserted further. Overall, 5/369 cases had changes in management
intraoperatively. In all five cases, abnormalities were suspected by clinician
judgment or abnormal ECAP measurements. Routine radiographs were completed in
349/369 cases and one was abnormal. This patient had known partial insertion due
to cochlear fibrosis from meningitis and abnormal radiograph did not result in
change in management. CONCLUSION: Clinician suspicion and/or abnormal ECAP
prompted suspicion for abnormal electrode placement prior to evaluation with
radiograph in all cases in which change in management occurred. Intraoperative
radiographs may be valuable in setting of clinical suspicion. Routine radiographs
do not result in change in management and are, therefore, unnecessary.
PMID- 28688565
TI - Diagnostic accuracy of a general practitioner with video-otoscopy collected by a
health care facilitator compared to traditional otoscopy.
AB - OBJECTIVE: Video-otoscopy is rapidly developing as a new method to diagnose
common ear disease and can be performed by trained health care facilitators as
well as by clinicians. This study aimed to compare remote asynchronous
assessments of video-otoscopy with otoscopy performed by a general practitioner.
METHOD: Children, aged 2-16 years, attending a health center in Johannesburg,
South Africa, were examined. An otologist performed otomicroscopy and a general
practitioner performed otoscopy. Video-otoscopy was performed by a health care
facilitator and video sequences were stored on a server for assessment by the
same general practitioner 4 and 8 weeks later. At all examinations, a diagnosis
was set and the tympanic membrane appearance was graded using the OMgrade-scale.
The otologist's otomicroscopic diagnosis was set as reference standard to compare
the accuracy of the two otoscopic methods. RESULTS: Diagnostic agreement between
otologist's otomicroscopic examination and the general practitioner's otoscopic
examination was substantial (kappa 0.66). Agreement between onsite otomicroscopy
and the general practitioners asynchronous video assessments were also
substantial (kappa 0.70 and 0.80). CONCLUSION: Video-otoscopy performed by a
health care facilitator and assessed asynchronously by a general practitioner had
similar or better accuracy compared to face-to-face otoscopy performed by a
general practitioner.
PMID- 28688566
TI - Dysphagia in healthy children: Characteristics and management of a consecutive
cohort at a tertiary centre.
AB - OBJECTIVE: Whereas the literature is replete with reports on complex children
with dysphagia (DP), the parameters characterizing non-neurologically impaired
(NNI) children have been underreported, leaving a substantial knowledge gap. We
set to characterize a consecutive cohort of NNI children, their management, and
outcomes. METHODS: We undertook a retrospective case series. Children (<18 years
old) attending a tertiary multidisciplinary swallowing clinic were eligible.
Patients with neuro-developmental, neuromuscular, or syndromic abnormalities were
excluded. Primary outcomes included demographics, co-morbidities, presentations,
McGill score, swallowing and airway abnormalities (and their predictors).
Secondary outcomes were interventions and management response. RESULTS: From 171
consecutive patients (37-month period), 128 were included (69 males, median age
6.6 months (0.5-124.2)). Significant clinical presentations included recurrent
pneumonias (20), cyanotic spells (14) and life-threatening events (10).
Swallowing assessments revealed laryngeal penetration (67), aspiration (25).
Other investigations included overnight oximetry (77), airway (70), and
gastrointestinal endoscopy (24); revealing laryngomalacia (29), laryngeal
mobility disorder (8), and subglottic stenosis (8). Non-surgical interventions
involved oral diet modifications (85) and enteral nutrition (15). Surgical
interventions included supraglottoplasties (18), endoscopic laryngeal cleft
repair (14), and injection (19). 119 patients received intervention and at last
follow-up (median 5.2 months (0.3-88.8)) 94 had improved. Of those treated 116
were on an unmodified oral diet, and 24 on a modified diet. ALTE and snoring
predicted airway abnormalities, recurrent pneumonia predicted swallowing
abnormalities, and age and airway lesions predicted the McGill score. CONCLUSION:
a significant proportion of NNI children with DP harbor airway and swallowing
abnormalities warranting endoscopic and instrumental assessment.
PMID- 28688567
TI - Factors influencing hearing outcomes in pediatric patients undergoing ossicular
chain reconstruction.
AB - OBJECTIVE: Ossicular chain disruption in children leads to conductive hearing
loss. Few studies have focused on factors influencing successful results in
pediatric ossicular chain reconstruction (OCR). We aim to determine whether
demographic or surgical factors affect hearing outcomes in pediatric OCR.
METHODS: We conducted a retrospective chart review of 120 patients undergoing OCR
at our institution, a tertiary care hospital, between 2003 and 2014, with median
length of follow-up of 2.2 years (range 0.1-9.3 years). Pediatric patients (<18
years old at time of surgical procedure) who had current procedural terminology
(CPT) codes of OCR, and available pre- and post-operative audiograms were
included in the study. Demographic information, surgical details, and pre- and
post-operative pure-tone averages (PTA), speech reception thresholds (SRT), and
air-bone gaps (ABG) were recorded from clinic notes, audiograms and operative
reports. Differences between PTA, SRT and ABG pre- and post-operatively, as well
as demographic and surgical factors, were evaluated using Wilcoxon rank-sum
tests. Factors influencing revision were evaluated using Log-rank tests. RESULTS:
A total of 120 patients (123 ears) were included. 35.8% of cases were revised,
most commonly due to displaced prostheses. 28.5% of surgeries resulted in normal
hearing (PTA <=25 dB) post-operatively. Post-operative SRT and ABG were
significantly better in patients with partial ossicular replacement prosthesis
(PORP) compared with those with total ossicular replacement prosthesis (TORP) (p
= 0.016, 0.027). Titanium prostheses resulted in better post-operative PTA and
larger changes in PTA compared with all other materials (p = 0.034, p = 0.038).
CONCLUSIONS: In our experience, children with titanium prostheses had better
hearing outcomes than those with other materials, and children with PORP had
better hearing outcomes than those with TORP.
PMID- 28688568
TI - Evaluation of speech in noise abilities in school children.
AB - This study aimed to analyze the perception of speech in noise in children with
poor school performance and to compare them with children with good school
performance, considering gender, age and ear side as variables. The
intelligibility of speech was evaluated in school children utilizing the
Brazilian Hearing in Noise Test (HINT) in the situations of quiet (Q), Left ear
competitive noise (NL), Right Ear Competitive Noise (NR), as well as the global
average of other hearing situations, denominated Noise Composite (NC). Ninety
seven school children between the ages of 8 and 10 were recruited in five schools
of Sao Paulo-Brazil; the control group (CG) consisted of 54 students (23 male/ 31
female) without language and/or speech difficulties and good school performance,
and the study group (SG) consisted of 43 students (28 male/ 15 female) identified
by their teachers as having poor school performance. The variables gender and ear
side did not interfere in speech perception. The age variable influenced only the
CG. The SG had worse performance than the CG in the Q, NF and NC conditions. NF
was the most difficult for both groups. The perception of speech in noise was the
worst in children with poor school performance. The variables gender and ear side
did not interfere in speech perception. The age group variable influenced the
performance of the group of children with good school performance, demonstrating
a better ability in older children. The speech perception in noise ability is
more difficult for both groups when the noise affects both ears.
PMID- 28688569
TI - Assessment of the feeding Swallowing Impact Survey as a quality of life measure
in children with laryngeal cleft before and after repair.
AB - OBJECTIVE: To cross-validate the Feeding Swallowing Impact Survey (FSIS), a
quality of life instrument, specifically to a subpopulation of children who
aspirate due to laryngeal cleft. INTRODUCTION: The FSIS is a recently validated
instrument used to describe caregiver quality of life (QOL) in children with
aspiration due to various causes. To cross-validate the FSIS specifically to the
subpopulation of children who aspirate due to laryngeal cleft, we tested the
hypotheses that caregivers would report significant different scores form
baseline if their children improved at the one year mark postintervention due to
either successful conservative or surgical measures (discriminant validity) and
would not report significant differences in their FSIS reporting if there was no
change in their child's aspiration at the one year mark post intervention
(convergent validity). METHODS: The FSIS was administered to the caregivers of 35
children (19 male, 16 female; age range: 5-79 months) who aspirate secondary to
known laryngeal cleft (diagnosed by suspension laryngoscopy and inspection). All
children had a baseline VFSS demonstrating aspiration and documenting what
feeding plan to follow and caregivers completed the FSIS at this point as well.
All children regardless of whether they were treated by conservative or surgical
intervention underwent a follow-up VFSS at the one year post-intervention mark
and the caregivers completed a FSIS at this time point as well. RESULTS: Among
two distinct sub-populations of children who underwent either successful
conservative or surgical treatment for their laryngeal cleft and demonstrated
improvement at the one year mark (as defined by a VFSS documented decreased need
for thickener by at least one consistency or more) and where we hypothesized that
FSIS scores would not be significantly different, the caregivers reported no
significant differences in FSIS scores cleft repair (mean FSIS scores 2.45 (SD
0.88)/2.1 (SD 0.94); p = 0.28). Moreover, as another test to convergent validity,
for children who underwent either unsuccessful conservative treatment (and
subsequently went on to need surgery) or who were not successfully surgically
treated for their laryngeal cleft and demonstrated no significant improvement at
the one year mark (as defined by a VFSS documented decreased need for thickener
by at least one consistency or more), the caregivers reported no significant
differences in FSIS scores cleft repair (mean FSIS scores 2.8(SD 0.79)/2.5(SD
0.88); p = 0.69). For divergent validity, two distinct sub-populations of
children who underwent either successful or not successful surgical treatment for
their laryngeal cleft (demonstrated by either improvement or lack of improvement
at the one year mark VFSS as defined by a decreased need for thickener by at
least one consistency or more) revealed significant differences in caregiver FSIS
scores cleft repair (mean FSIS scores 1.38 (SD 0.32); 32.8 (SD 0.79); p=<0.0002).
DISCUSSION: This results of this study provide convergent and divergent validity
supporting the cross-validation of the FSIS instrument to be utilized as a
validated QOL instrument to evaluate children with aspiration specifically due
laryngeal cleft as another tool with which to evaluate the outcomes of medical or
surgical interventions for this disorder.
PMID- 28688570
TI - Congenital nasal obstruction in infants: A retrospective study and literature
review.
AB - OBJECTIVES: To identify etiologies of congenital nasal obstruction and describe
clinical practice patterns in the evaluation, diagnosis, and treatment of
symptomatic infants. METHODS: An electronic chart review from 1/1/2006-10/1/2016
for all patients with a diagnosis of nasal obstruction within the first six
months of life using ICD-9 and 10 codes 478.19 and J34.89. RESULTS: A total of 34
patients were evaluated by the Division of Otolaryngology for this chief
complaint. 38% of neonates were born premature and 32% were admitted to the NICU
at birth, with a female-to-male ratio of 1:1.4. Presenting signs and symptoms
included: stertor (44%), cyanosis (24%), stridor (24%), retractions (21%),
rhinorrhea (21%), apnea (12%), and epistaxis (8%). 47% of patients received
ancillary radiographic imaging (CT or MRI). Diagnoses observed include: midnasal
stenosis (38%), pyriform aperture stenosis (21%), choanal stenosis (12%),
dacryocystocele (6%), microrhinia (6%), septal deviation (6%), nasopharyngeal
reflux (3%), nasopharyngeal teratoma (3%), neonatal rhinitis (3%), and pharyngeal
wall collapse (3%). 71% of patients were noted to have bilateral nasal
obstruction. 41% of infants were found to have an associated ear, nose, and
throat anomaly. 15% of patients required surgical intervention. The mean time-to
resolution was 240 days. CONCLUSION: Congenital nasal obstruction has a broad
differential diagnosis: the timing, onset, and laterality of symptoms can provide
insights into the source of upper airway compromise. Most infants improve through
conservative management (i.e. suctioning, humidification) and medical therapies
(i.e. intranasal drops, nasal sprays).
PMID- 28688571
TI - Local effects of epidermal growth factor on the wound healing in esophageal
anastomosis: An experimental study.
AB - OBJECTIVE: In this study with the experimental model of primary repair of
esophageal atresia(EA), we investigated the effects of the epidermal growth
factor(EGF) on wound healing in the anastomosis of EA. MATERIALS AND METHODS:
Forty rabbits that were performed a resection of a 1-cm segment of the cervical
esophagus followed by the end-to-end anastomosis were divided into four groups.
Group I (7-day group) and III (21-day group), the control groups, had no EGF
applied to the anastomosis. In group II (7-day group) and group III (21-day
group), all around the anastomoses were locally covered with 100 MUg/kg EGF.
Group 1, 2 and 3, 4 were sacrificed on the 7th and 21st day, respectively. We
investigated and compared with bursting pressure, vascularization around the
anastomotic line by histopathology, inflammation, and fibroblast granulation as
well as hydroxyproline level by biochemical. RESULTS: No significant difference
was found at vascularization and inflammation between all of the groups (p >
0.05). Considering the critical parameters of the groups, at bursting pressure
difference was found between group 1 and 2 as well as 3 and (p < 0.05). At
fibroblast granulation and hydroxyproline level, no difference was found between
group 1 and 2 (p > 0.05) but the difference between group 3 and 4 (p < 0.05).
CONCLUSION: EGF might be useful in preventing anastomotic leakage of esophageal
atresia in primary anastomosis of esophageal atresia by accelerating wound
healing process and increasing the stability of the anastomotic line.
PMID- 28688572
TI - Visual cortex activation decrement following cochlear implantation in prelingual
deafened children.
AB - OBJECTIVE: Visual take-over of the auditory cortex in prelingual deaf children
has been widely reported. However, there have been few studies on visual cortex
plasticity after cochlear implantation (CI). In this study, we investigated the
hypothesis that extrinsic auditory stimulation following CI in prelingual
deafened children can induce visual cortex plasticity. METHOD: Visual evoked
potentials (VEPs) were recorded in 37 CI children (4 groups with different use
times) and 8 control subjects, in response to sound and nonsound stimuli. Latency
and amplitude were analyzed for the P1, N1 and P2 components on the Oz electrode.
Comparisons of VEP were conducted between the sound and nonsound stimuli and
among different groups in order to view evidence of visual cortex reorganization.
RESULTS: The latency of the P2 component was significantly longer at the
occipital site (Oz) in CI 0M than those in the other four groups. After the
effect of age was excluded, a significant negative correlation was found between
CI usage and P2 latency of nonsound stimuli. Occipital P1N1 latency and P1
amplitude were not affected by group or stimulus category. However, the N1 and P2
amplitudes were significantly larger in response to a sound stimulus than to a
nonsound stimulus. CONCLUSION: Our findings suggest that P2 latency develops with
CI usage and may be a biomarker of visual cortex plasticity.
PMID- 28688573
TI - Comparison between selective and routine intensive care unit admission post
supraglottoplasty.
AB - OBJECTIVE: To compare major post-operative respiratory complications, post
operative disposition and duration of hospital admission before and after
adopting a selective intensive care unit (ICU) admission care plan following
supraglottoplasty (SGP). METHODS: Retrospective case series set in a tertiary
pediatric referral center. Eligible patients undergoing SGP between October 2003
and July 2015 were identified through a prospectively kept surgical database.
Historical cohorts with routine admission to ICU and selective admission to ICU
were identified based on a shift in surgeon practice. The cohorts were compared
with respect to demographics, presenting features, endoscopic findings, baseline
sleep and swallowing study results, major respiratory complications (including
repeat or unplanned ICU admission or intubation) and length of post-operative
hospital admission. RESULTS: 141 eligible patients were identified with 35
children in the routine ICU admission cohort and 106 in the selective ICU
admission cohort. There were no significant differences between cohorts regarding
major respiratory complications with only one patient in the selective ICU
admission cohort requiring an unplanned admission to ICU (P = 1.00, Fisher's
exact test). This gives a number needed to harm of 78 step-down unit admissions
for 1 unplanned ICU admission. The rate of ICU admission was reduced from 71% to
26% with adoption of a selective ICU admission care plan (p < 0.01, chi2). Mean
duration of post-operative hospitalization was reduced from 5.1 +/- 3.5 days to
1.9 +/- 2.3 days (P < 0.01, Student's t-test). CONCLUSIONS: Selective post
operative ICU admission following SGP significantly reduces ICU utilization and
may reduce length of hospital stay without compromising safety and care. This has
significant cost benefit implications.
PMID- 28688574
TI - Clinical and bacteriological differences of deep neck infection in pediatric and
adult patients: Review of 123 cases.
AB - OBJECTIVES: Deep neck infections (DNIs) can lead to life-threatening disease.
However, the detailed pathophysiology remains unclear due to its rarity and only
a few reports have directly compared DNIs in children and adults. This study
aimed to reveal the clinical differences between DNIs in children and adults.
METHODS: We retrospectively reviewed 123 patients who suffered from DNIs at
Tohoku University Hospital from August 2005 to July 2015. We extracted data on
patient sex, age, antecedent illness, extension of infections, operative
procedures, and bacteriology results. The patients were categorized into
pediatric (<=18 years) and adult (>18 years) groups. Fisher's exact test was
performed to determine significant differences between the two groups. RESULTS:
Fifteen children (6 males and 9 females) and 108 adults (71 males and 37 females)
were identified. The most common antecedent illness in pediatric patients was
lymphadenitis, which was the least common in adult patients (73% vs 7%, p <
0.0001). The incidence of DNIs extending below the hyoid bone was significantly
lower in pediatric patients than in adult patients (20% vs 53%, p < 0.05).
Regarding bacterial culture analysis, Staphylococcus species was the most common
pathogen in children (60%), whereas only 9% of adults were positive for
Staphylococcus (p < 0.001). Streptococcus species were significantly less common
in children than in adults (27% vs 56%, p = 0.05). Anaerobes were also
significantly less common in children than in adults (13% vs 45%, p < 0.01).
Concerning surgical intervention, 53% of pediatric patients underwent external
incision compared with 70% of adults. Specifically, tracheostomy was
significantly less frequently performed in children than in adults (7% vs 54%, p
< 0.01). CONCLUSION: DNIs in children feature different characteristics from
those in adults regarding severity, antecedent illness, bacteriology, and
clinical management.
PMID- 28688575
TI - Natural-Product Antibiotics: Cues for Modulating Bacterial Biofilm Formation.
AB - Cell-cell communication enables bacteria to coordinate their behavior through the
production, recognition, and response to chemical signals produced by their
microbial neighbors. An important example of coordinated behavior in bacteria is
biofilm formation, where individual cells organize into highly complex, matrix
encased communities that differentiate into distinct cell types and divide labor
among individual cells. Bacteria rely on environmental cues to influence biofilm
development, including chemical cues produced by other microbes. A multitude of
recent studies have demonstrated that natural-product antibiotics at
subinhibitory concentrations can impact biofilm formation in neighboring
microbes, supporting the hypothesis that these compounds may have evolved as
signaling molecules that mediate cell-cell interactions. In this review we
discuss the role of antibiotics in modulating biofilm formation and interspecies
communication in bacteria.
PMID- 28688577
TI - Re: Association between Imaging Characteristics and Different Molecular Subtypes
of Breast Cancer.
PMID- 28688576
TI - VAMP8-mediated NOX2 recruitment to endosomes is necessary for antigen release.
AB - Cross-presentation of foreign antigen in major histocompatibility complex (MHC)
class I by dendritic cells (DCs) requires activation of the NADPH-oxidase NOX2
complex. We recently showed that NOX2 is recruited to phagosomes by the SNARE
protein VAMP8 where NOX2-produced reactive oxygen species (ROS) cause lipid
oxidation and membrane disruption, promoting antigen translocation into the
cytosol for cross-presentation. In this study, we extend these findings by
showing that VAMP8 is also involved in NOX2 trafficking to endosomes. Moreover,
we demonstrate in both human and mouse DCs that absence of VAMP8 leads to
decreased ROS production, lipid peroxidation and antigen translocation, and that
this impairs cross-presentation. In contrast, knockdown of VAMP8 did not affect
recruitment of MHC class I and the transporter associated with antigen processing
1 (TAP1) to phagosomes, although surface levels of MHC class I were reduced.
Thus, in addition to a secretory role, VAMP8-mediates trafficking of NOX2 to
endosomes and phagosomes and this promotes induction of cytolytic T cell immune
responses.
PMID- 28688578
TI - Reply to: The Choice of Prior in Bayesian Modeling of the Information Sampling
Task.
PMID- 28688580
TI - The Choice of Prior in Bayesian Modeling of the Information Sampling Task.
PMID- 28688579
TI - Replicable and Coupled Changes in Innate and Adaptive Immune Gene Expression in
Two Case-Control Studies of Blood Microarrays in Major Depressive Disorder.
AB - BACKGROUND: Peripheral inflammation is often associated with major depressive
disorder (MDD), and immunological biomarkers of depression remain a focus of
investigation. METHODS: We used microarray data on whole blood from two
independent case-control studies of MDD: the GlaxoSmithKline-High-Throughput
Disease-specific target Identification Program [GSK-HiTDiP] study (113 patients
and 57 healthy control subjects) and the Janssen-Brain Resource Company study (94
patients and 100 control subjects). Genome-wide differential gene expression
analysis (18,863 probes) resulted in a p value for each gene in each study. A
Bayesian method identified the largest p-value threshold (q = .025) associated
with twice the number of genes differentially expressed in both studies compared
with the number of coincidental case-control differences expected by chance.
RESULTS: A total of 165 genes were differentially expressed in both studies with
concordant direction of fold change. The 90 genes overexpressed (or UP genes) in
MDD were significantly enriched for immune response to infection, were
concentrated in a module of the gene coexpression network associated with innate
immunity, and included clusters of genes with correlated expression in monocytes,
monocyte-derived dendritic cells, and neutrophils. In contrast, the 75 genes
underexpressed (or DOWN genes) in MDD were associated with the adaptive immune
response and included clusters of genes with correlated expression in T cells,
natural killer cells, and erythroblasts. Consistently, the MDD patients with
overexpression of UP genes also had underexpression of DOWN genes (correlation >
.70 in both studies). CONCLUSIONS: MDD was replicably associated with
proinflammatory activation of the peripheral innate immune system, coupled with
relative inactivation of the adaptive immune system, indicating the potential of
transcriptional biomarkers for immunological stratification of patients with
depression.
PMID- 28688581
TI - Persistent and inducible neogenesis repopulates progenitor renin lineage cells in
the kidney.
AB - Renin lineage cells (RLCs) serve as a progenitor cell reservoir during
nephrogenesis and after renal injury. The maintenance mechanisms of the RLC pool
are still poorly understood. Since RLCs were also identified as a progenitor cell
population in bone marrow we first considered that these may be their source in
the kidney. However, transplantation experiments in adult mice demonstrated that
bone marrow-derived cells do not give rise to RLCs in the kidney indicating their
non-hematopoietic origin. Therefore we tested whether RLCs develop in the kidney
through neogenesis (de novo differentiation) from cells that have never expressed
renin before. We used a murine model to track neogenesis of RLCs by flow
cytometry, histochemistry, and intravital kidney imaging. During nephrogenesis
RLCs first appear at e14, form a distinct population at e16, and expand to reach
a steady state level of 8-10% of all kidney cells in adulthood. De novo
differentiated RLCs persist as a clearly detectable population through
embryogenesis until at least eight months after birth. Pharmacologic stimulation
of renin production with enalapril or glomerular injury induced the rate of RLC
neogenesis in the adult mouse kidney by 14% or more than three-fold,
respectively. Thus, the renal RLC niche is constantly filled by local de novo
differentiation. This process could be stimulated consequently representing a new
potential target to beneficially influence repair and regeneration after kidney
injury.
PMID- 28688583
TI - Image improvement method for positron emission mammography.
AB - PURPOSE: To evaluate in clinical use a rapidly converging, efficient iterative
deconvolution algorithm (RSEMD) for improving the quantitative accuracy of
previously reconstructed breast images by a commercial positron emission
mammography (PEM) scanner. MATERIALS AND METHODS: The RSEMD method was tested on
imaging data from clinical Naviscan Flex Solo II PEM scanner. This method was
applied to anthropomorphic like breast phantom data and patient breast images
previously reconstructed with Naviscan software to determine improvements in
image resolution, signal to noise ratio (SNR) and contrast to noise ratio (CNR).
RESULTS: In all of the patients' breast studies the improved images proved to
have higher resolution, contrast and lower noise as compared with images
reconstructed by conventional methods. In general, the values of CNR reached a
plateau at an average of 6 iterations with an average improvement factor of about
2 for post-reconstructed Flex Solo II PEM images. Improvements in image
resolution after the application of RSEMD have also been demonstrated.
CONCLUSIONS: A rapidly converging, iterative deconvolution algorithm with a
resolution subsets-based approach (RSEMD) that operates on patient DICOM images
has been used for quantitative improvement in breast imaging. The RSEMD method
can be applied to PEM images to enhance the resolution and contrast in cancer
diagnosis to monitor the tumor progression at the earliest stages.
PMID- 28688584
TI - Foundations of Pediatrics: Lawson Wilkins, MD (1894-1963).
PMID- 28688582
TI - Net K+ secretion in the thick ascending limb of mice on a low-Na, high-K diet.
AB - Because of its cardio-protective effects, a low-Na, high-K diet (LNaHK) is often
warranted in conjunction with diuretics to treat hypertensive patients. However,
it is necessary to understand the renal handling of such diets in order to choose
the best diuretic. Wild-type (WT) or Renal Outer Medullary K channel (ROMK)
knockout mice (KO) were given a regular (CTRL), LNaHK, or high-K diet (HK) for 4
7 days. On LNaHK, mice treated with either IP furosemide for 12 hrs, or given
furosemide in drinking water for 7 days, exhibited decreased K clearance. We used
free-flow micropuncture to measure the [K+] in the early distal tubule (EDT [K+])
before and after furosemide treatment. Furosemide increased the EDT [K+] in WT on
CTRL but decreased that in WT on LNaHK. Furosemide did not affect the EDT [K+] of
KO on LNaHK or WT on HK. Furosemide-sensitive Na+ excretion was significantly
greater in mice on LNaHK than those on CTRL or HK. Patch clamp analysis of split
open TALs revealed that 70-pS ROMK exhibited a higher open probability (Po) but
similar density in mice on LNaHK, compared with CTRL. No difference was found in
the density or Po of the 30 pS K channels between the two groups. These results
indicate mice on LNaHK exhibited furosemide-sensitive net K+ secretion in the TAL
that is dependent on increased NKCC2 activity and mediated by ROMK. We conclude
that furosemide is a K-sparing diuretic by decreasing the TAL net K+ secretion in
subjects on LNaHK.
PMID- 28688585
TI - Alternatives in the Treatment of Short Stature.
PMID- 28688586
TI - Immunization Update VI.
PMID- 28688587
TI - Childhood Cancer Survivorship and Long-Term Outcomes.
PMID- 28688588
TI - Pediatric Thyroid Cancer.
PMID- 28688589
TI - Current Management for Pediatric Urologic Oncology.
PMID- 28688590
TI - Contemporary Management of Appendicitis in Children.
PMID- 28688591
TI - Management of Pediatric Intestinal Failure.
PMID- 28688592
TI - Bariatric Surgery: The Future of Obesity Management in Adolescents.
PMID- 28688593
TI - Emerging Infectious Diseases.
PMID- 28688594
TI - Biliary Atresia: Epidemiology, Genetics, Clinical Update, and Public Health
Perspective.
PMID- 28688595
TI - Dental Caries: An Update on Dental Trends and Therapy.
PMID- 28688596
TI - Effects of Inhaled Corticosteroids on Growth, Bone Metabolism, and Adrenal
Function.
PMID- 28688597
TI - Telehealth: No Longer an Idea for the Future.
PMID- 28688598
TI - The Impact of Cumulative Sociodemographic Risk Factors on the Home Environment
and Vocabulary in Early Childhood.
PMID- 28688599
TI - Designing and Implementing an Early Childhood Health and Development Program in
Rural, Southwest Guatemala: Lessons Learned and Future Directions.
PMID- 28688600
TI - New Nephrological Frontiers: Opportunities and Challenges Created by Fetal Care
Centers.
PMID- 28688601
TI - New Concepts in Food Allergy: The Pediatric Gastroenterologist's View.
PMID- 28688602
TI - Introduction.
PMID- 28688604
TI - Serum concentrations of per- and poly-fluoroalkyl substances and factors
associated with exposure in the general adult population in South Korea.
AB - Per- and polyfluoroalkyl substances (PFASs) are ubiquitous contaminants found
worldwide, including in South Korea. As a result, they are frequently detected in
Koreans. However, there is limited representative data and information on
potential sources in Korea. Therefore, we measured the serum concentrations of
ten PFASs in nationally representative samples of the Korean population (n=1874,
18-69 years) and evaluated the factors associated with their exposure. Serum
PFOS, PFDA, PFOA, and PFNA were detected in nearly all participants (83.1-99.9%).
However, serum PFPA, PFHxA, and PFHpA were almost undetected (<0.5% of
participants). PFOS had the highest population-weighted geometric mean of
10.23ng/mL (95% CI: 9.99-10.47), which was followed by PFOA with 2.85ng/mL (95%
CI: 2.73-2.97) and PFDA with 2.17ng/mL (95% CI: 2.12-2.23). PFNA, PFDA, PFHxS,
PFOA, and PFOS concentrations were higher in males (p<0.001) and older adults
(p<0.001). PFNA was higher in those who used wax, polish, and water-resistant
materials (adjusted proportional change=1.14; 95% CI: 1.08-1.22), and those who
ate cooked fish (1.16; 95% CI: 1.03-1.31) compared to those who ate nearly no
fish. PFDA was higher in those who used herbicides and pesticides (1.05; 95% CI:
1.02-1.09), those who drank beverages in a plastic bag on a daily basis (1.10;
95% CI: 1.03-1.19), and those who ate raw fish (1.15; 95% CI: 1.03-1.29) or
cooked fish (1.13; 95% CI: 1.05-1.23) compared to those who ate nearly no fish.
PFHxS was higher in those who used traditional Korean health supplement foods
(1.08; 95% CI: 1.01-1.15). PFOA was higher in those who used plastic wrap in a
microwave daily or weekly (1.08; 95% CI: 1.00-1.16), and those who used
disposable paper cups (1.07; 95% CI: 1.01-1.13). PFOS was lower in underweight
participants (0.84; 95%CI: 0.75-0.93) compared to those who were obese, and
higher in those who exercised regularly (1.08; 95% CI: 1.03-1.14) or irregularly
(1.06, 95% CI: 1.01-1.12) compared to those who did not exercise. Subjects who
used severely damaged Teflon appliances had lower concentrations of PFOA (0.78,
95% CI: 0.65-0.95), while regular use of Gore-Tex goods was related to higher
PFNA (1.15, 95% CI: 1.03-1.28) and PFDA (1.11; 95% CI: 1.02-1.20) levels. These
findings suggest that most Koreans are frequently exposed to PFASs, and that
serum concentrations of PFASs vary with age, sex, and exposure factors.
PMID- 28688605
TI - Human papillomavirus prevalence in the anus and urine among HIV-infected Japanese
men who have sex with men.
AB - BACKGROUND: The present study investigated human papillomavirus (HPV) prevalence
in anal and urine samples, and evaluated cytological findings among human
immunodeficiency virus (HIV)-infected Japanese men who have sex with men (MSM).
METHODS: A total of 148 patients were enrolled. Anal and urine samples were
collected from each participant, and a HPV-DNA test and genotyping were performed
using flow-through hybridization. In addition, anal cytology was evaluated based
on Papanicolaou staining. Questionnaires regarding lifestyle habits and sexual
behavior were obtained. RESULTS: The beta-globin gene was positive in 131 (88.5%)
anal samples and 139 (94.0%) urine samples. Among the beta-globin-positive
samples, the HPV prevalence in anal and urine samples was 80.9% and 30.9%,
respectively. High-risk HPV (HR-HPV) was detected in 57.3% of anal samples and
20.9% of urine samples. Among 122 adequate cytological samples, anal cytological
abnormalities were observed in 99 cases (81.1%). Anal cytological tests revealed
that atypical squamous cells of an undetermined significance (ASCUS) were
detected in 57 (46.7%) patients, followed by low-grade squamous intraepithelial
lesions (SIL) in 35 (28.7%), high-grade SIL in five (4.1%), and atypical squamous
cells cannot exclude high-grade SIL (ASC-H) in two (1.6%), respectively. The
nadir counts of CD4-positive T-lymphocyte less than 200 MUL and anal HR-HPV
infection were independent risk factors for anal cytological atypia over ASC-H.
CONCLUSIONS: The present study demonstrated high HPV prevalence in the anus and
urine, and showed a high incidence of anal cytological atypia associated with HR
HPV infections among HIV-infected MSM patients.
PMID- 28688607
TI - Will the 8th editions of the UICC & AJCC staging manuals improve the pathological
diagnosis of extranodal extension from cervical lymph nodes?
PMID- 28688606
TI - A clinical and neurophysiological motor signature of Unverricht-Lundborg disease.
AB - OBJECTIVES: Unverricht-Lundborg disease (ULD) is the most common form of
progressive myoclonus epilepsy. Cerebellar dysfunction may appear over time,
contributing along with myoclonus to motor disability. The purpose of the present
work was to clarify the motor and neurophysiological characteristics of ULD
patients. METHODS: Nine patients with genetically proven ULD were evaluated
clinically (medical history collected from patient charts, the Scale for the
Assessment and Rating of Ataxia and Unified Myoclonus Rating Scale).
Neurophysiological investigations included EEG, surface polymyography, long-loop
C-reflexes, somatosensory evoked potentials, EEG jerk-locked back-averaging
(JLBA) and oculomotor recordings. All patients underwent brain MRI. Non
parametric Mann-Whitney tests were used to compare ULD patients' oculomotor
parameters with those of a matched group of healthy volunteers (HV). RESULTS:
Myoclonus was activated by action but was virtually absent at rest and poorly
induced by stimuli. Positive myoclonus was multifocal, often rhythmic and of
brief duration, with top-down pyramidal temporospatial propagation. Cortical
neurophysiology revealed a transient wave preceding myoclonus on EEG JLBA (n=8),
enlarged somatosensory evoked potentials (n=7) and positive long-loop C-reflexes
at rest (n=5). Compared with HV, ULD patients demonstrated decreased saccadic
gain, increased gain dispersion and a higher frequency of hypermetric saccades
associated with decreased peak velocity. CONCLUSION: A homogeneous motor pattern
was delineated that may represent a ULD clinical and neurophysiological
signature. Clinical and neurophysiological findings confirmed the pure cortical
origin of the permanent myoclonus. Also, oculomotor findings shed new light on
ULD pathophysiology by evidencing combined midbrain and cerebellar dysfunction.
PMID- 28688608
TI - Down-regulated microRNA-375 expression as a predictive biomarker in non-small
cell lung cancer brain metastasis and its prognostic significance.
AB - Brain metastases (BM) are common among patients with non-small cell lung cancer
(NSCLC) and have been associated with significant morbidity and limited survival.
Early and sensitive detection of BM is essential for improving prognosis.
Recently, microRNA-375(miR-375) which is specifically expressed in the brain has
been found significantly dysregulated in many human cancers. However, there is
still no data whether miR-375 is associated with higher risk of BM development in
NSCLC. In this study, we detected the miR-375 expression using quantitative real
time PCR (qRT-PCR) and assessed its predictive and prognostic significance. Our
result showed that miR-375 expression was significantly down-regulated in NSCLC
patients with BM(BM+, N=30) compared with NSCLC without BM(BM-, N=30) (P<0.001).
Statistical analysis indicated that low miR-375 expression was linked to advanced
disease stage (P<0.001) and brain metastasis (P<0.001) in NSCLC patient. Survival
analysis suggested that low-expression group had significantly shorter overall
survival than high-expression group in NSCLC patients with BM(log-rank test:
P<0.05) as well as the total cases(log-rank test: P<0.01). Multivariate Cox
proportional hazards model analysis indicated that low miR-375 expression was
independently linked to poor survival of patients with NSCLC (HR=5.48, 95% CI:
1.93-15.56, P=0.001). In addition, we found that VEGF and MMP-9 were over
expressed in down-regulated miR-375 expression cases. Collectively, this study
demonstrated that miR-375 may play an important role as a predictive biomarker in
brain metastasis and an independent prognostic factor in NSCLC. Over-expression
of VEGF and MMP-9 may be the reason for poor prognosis of NSCLC patients with low
miR-375 expression.
PMID- 28688609
TI - Does restoration of hip center with subtrochanteric osteotomy provide preferable
outcome for Crowe type III-IV irreducible development dysplasia of the hip??
AB - BACKGROUND: Subtrochanteric osteotomy and proximal placement of acetabular
components are two common procedures used to manage irreducible, high riding
developmental dysplasia of the hip (DDH). Some common and specific complications
are observed in both procedures. We aimed to compare both the outcomes and
complications between these two procedures. METHODS: Twenty-one patients with
unilateral, Crowe type III-IV DDH who were seen between 2002 and 2014 were
included in this study. Subtrochanteric osteotomy with restoration of the hip
center and proximal placement of the acetabular component were performed on 10
and 11 patients, respectively. Harris hip score (HHS) and radiographic images
were used for outcome assessment. All patients completed a minimum of 2-year
follow-up. RESULTS: The HHS in patients who had undergone subtrochanteric
osteotomy and proximal placement of the acetabular component were 89.4 and 91.9
points, respectively. However, this difference was not significant. There were
six complications, including transient sciatic nerve palsy in two patients,
nonunion at the junction in two, an intra-operative fracture in one and cup
loosening in another. The complication rates in the subtrochanteric osteotomy and
proximal placement of the acetabular component group were 30% and 27.5%,
respectively. CONCLUSION: With regard to both clinical outcomes and complication
rates, restoration of the hip center using subtrochanteric osteotomy may provide
similar benefits to those patients with proximal placement of the acetabular
component in treating Crowe type III-IV DDH.
PMID- 28688610
TI - [Materials for the paediatric resuscitation trolley or backpack: Expert
recommendations].
AB - Cardio-respiratory arrest (CPA) is infrequent in children, but it can occur in
any place and at any time. This fact means that every health care facility must
always have the staff and material ready to resuscitate a child. These
recommendations are the consensus of experts of the Spanish Paediatric and
Neonatal Resuscitation Group on the material and medication for paediatric and
neonatal resuscitation and their distribution and use. CPR trolleys and backpacks
must include the essential material to quickly and efficiently perform a
paediatric CPR. At least one CPR trolley must be available in every Primary Care
facility, Paediatric Intensive Care Unit, Emergency Department, and Pre-hospital
Emergency Areas, as well as in paediatric wards, paediatric ambulatory areas, and
radiology suites. This trolley must be easily accessible and exclusively include
the essential items to perform a CPR and to assist children (from newborns to
adolescents) who present with a life-threatening event. Such material must be
familiar to all healthcare staff and also include the needed spare parts, as well
as enough drug doses. It must also be re-checked periodically. The
standardisation and unification of the material and medication of paediatric CPR
carts, trolleys, and backpacks, as well as the training of the personnel in their
use are an essential part of the paediatric CPR.
PMID- 28688611
TI - Reply to Jae Heon Kim, Bora Lee, and Benjamin I. Chung's Letter to the Editor re:
Sungmin Woo, Chong Hyun Suh, Sang Youn Kim, Jeong Yeon Cho, Seung Hyup Kim.
Diagnostic Performance of Magnetic Resonance Imaging for the Detection of Bone
Metastasis in Prostate Cancer: A Systematic Review and Meta-analysis. Eur Urol.
In press. http://dx.doi.org/10.1016/j.eururo.2017.03.042.
PMID- 28688612
TI - Comprehensive Molecular Characterization of Urothelial Bladder Carcinoma: A Step
Closer to Clinical Translation?
PMID- 28688613
TI - Brachytherapy Boost Utilization and Survival in Unfavorable-risk Prostate Cancer.
AB - BACKGROUND: There are limited comparative survival data for prostate cancer (PCa)
patients managed with a low-dose rate brachytherapy (LDR-B) boost and dose
escalated external-beam radiotherapy (DE-EBRT) alone. OBJECTIVE: To compare
overall survival (OS) for men with unfavorable PCa between LDR-B and DE-EBRT
groups. DESIGN, SETTING, AND PARTICIPANTS: Using the National Cancer Data Base,
we identified men with unfavorable PCa treated between 2004 and 2012 with
androgen suppression (AS) and either EBRT followed by LDR-B or DE-EBRT (75.6
86.4Gy). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Treatment selection was
evaluated using logistic regression and annual percentage proportions. OS was
analyzed using the Kaplan-Meier method, log-rank test, Cox proportional hazards,
and propensity score matching. RESULTS AND LIMITATION: We identified 25038 men
between 2004 and 2012, during which LDR-B boost utilization decreased from 29% to
14%. LDR-B was associated with better OS on univariate (7-yr OS: 82% vs 73%;
p<0.001) and multivariate analyses (hazard ratio [HR] 0.70, 95% confidence
interval [CI] 0.64-0.77). Propensity score matching verified an OS benefit
associated with LDR-B boost (HR 0.74, 95% CI 0.66-0.89). The OS benefit of LDR-B
boost persisted when limited to men aged <60 yr with no comorbidities. On subset
analysis, there was no interaction between treatment and age, risk group, or
radiation dose. Limitations include the retrospective design, nonrandomized
selection bias, and the absence of treatment toxicity, hormone duration, and
cancer-specific outcomes. CONCLUSIONS: Between 2004 and 2012, LDR-B boost
utilization declined and was associated with better OS compared to DE-EBRT alone.
LDR-B boost is probably the ideal treatment option for men with unfavorable PCa,
pending long-term results of randomized trials. PATIENT SUMMARY: We compared
radiotherapy utilization and survival for prostate cancer (PCa) patients using a
national database. We found that low-dose rate brachytherapy (LDR-B) boost, a
method being used less frequently, was associated with better overall survival
when compared to dose-escalated external-beam radiotherapy alone for men with
unfavorable PCa. Randomized trials are needed to confirm that LDR-B boost is the
ideal treatment.
PMID- 28688614
TI - Re: Emmanuel S. Antonarakis, Changxue Lu, Brandon Luber, et al. Clinical
Significance of Androgen Receptor Splice Variant-7 mRNA Detection in Circulating
Tumor Cells of Men with Metastatic Castration-resistant Prostate Cancer Treated
with First- and Second-line Abiraterone and Enzalutamide. J Clin Oncol
2017;35:2149-56: AR-V7 Testing: What's in it for the Patient?
PMID- 28688615
TI - Innovative dairy cow management to improve resistance to metabolic and infectious
diseases during the transition period.
AB - The incidence of metabolic and infectious diseases varies greatly during the
lactation cycle. Most new cases of clinical mastitis appear at the beginning of
lactation, and the incidence increases with the level of milk production. In
addition to mastitis, many other infectious diseases become clinically apparent
during the first 2weeks of lactation. During this time, cows are in a negative
energy balance and must mobilize body reserves to balance the deficit between
food energy intake and energy required for milk production. The relationships
between energy deficit and metabolic diseases, such as ketosis and hepatic
lipidosis, are well known. Furthermore, cows in energy deficit have a weakened
immune system and are therefore more susceptible to infections. There is now good
evidence that the increase in circulating non-esterified fatty acids impairs
immune cell functions. Therefore, management approaches that reduce the negative
energy balance and the increase in non-esterified fatty acids at the beginning of
lactation are likely to improve resistance to infection. Improving the nutrient
supply through periparturient nutritional management has been the subject of
considerable research. However, another way to reduce the imbalance between
nutrient supply and demand is to temporarily decrease the latter. In this review,
we examine how management strategies such as conjugated linoleic acid feeding,
prepartum milking, or limiting postpartum milk production could be used to reduce
metabolic perturbations and immunosuppression during the transition period. At
this stage, it appears that reducing the amount of milk harvested postpartum by
means of partial milking in the first days after calving is the most promising
approach to reduce metabolic stress and immunosuppression without compromising
the productivity of high-yielding dairy cows.
PMID- 28688616
TI - Current possibilities of liquid chromatography for the characterization of
antibody-drug conjugates.
AB - Antibody Drug Conjugates (ADCs) are innovative biopharmaceuticals gaining
increasing attention over the last two decades. The concept of ADCs lead to new
therapy approaches in numerous oncological indications as well in infectious
diseases. Currently, around 60 CECs are in clinical trials indicating the
expanding importance of this class of protein therapeutics. ADCs show
unprecedented intrinsic heterogeneity and address new quality attributes which
have to be assessed. Liquid chromatography is one of the most frequently used
analytical method for the characterization of ADCs. This review summarizes recent
results in the chromatographic characterization of ADCs and supposed to provide a
general overview on the possibilities and limitations of current approaches for
the evaluation of drug load distribution, determination of average drug to
antibody ratio (DARav), and for the analysis of process/storage related
impurities. Hydrophobic interaction chromatography (HIC), reversed phase liquid
chromatography (RPLC), size exclusion chromatography (SEC) and multidimensional
separations are discussed focusing on the analysis of marketed ADCs. Fundamentals
and aspects of method development are illustrated with applications for each
technique. Future perspectives in hydrophilic interaction chromatography (HILIC),
HIC, SEC and ion exchange chromatography (IEX) are also discussed.
PMID- 28688617
TI - Critical review of surface-enhanced Raman spectroscopy applications in the
pharmaceutical field.
AB - Surface-enhanced Raman spectroscopy (SERS) is a sensitive analytical tool used in
the pharmaceutical field in recent years. SERS keeps all the advantages of
classical Raman spectroscopy while being is more sensitive allowing its use for
the detection and the quantification of low-dose substances contained in
pharmaceutical samples. However, the analytical performance of SERS is limited
due to the difficulty to implement a quantitative methodology correctly
validated. Nevertheless, some studies reported the development of SERS
quantitative methods especially in pharmaceutical approaches. In this context,
this review presents the main concepts of the SERS technique. The different steps
that need to be applied to develop a SERS quantitative method are also deeply
described. The last part of the present manuscript gives a critical overview of
the different SERS pharmaceutical applications that were developed for a non
exhaustive list of pharmaceutical compounds with the aim to highlights the
validation criteria for each application.
PMID- 28688618
TI - Nonlinear integral sliding mode control design of photovoltaic pumping system:
Real time implementation.
AB - The aim of this paper is to provide high performance control of pumping system.
The proposed method is designed by an indirect field oriented control based on
Sliding Mode (SM) technique. The first contribution of this work is to design
modified switching surfaces which presented by adding an integral action to the
considered controlled variables. Then, in order to prevent the chattering
phenomenon, modified nonlinear component is developed. The SM concept and a
Lyapunov function are combined to compute the Sliding Mode Control (SMC) gains.
Besides, the motor performance is validated by numeric simulations and real time
implementation using a dSpace system with DS1104 controller board. Also, to show
the effectiveness of the proposed approach, the obtained results are compared
with other techniques such as conventional PI, Proportional Sliding Mode (PSM)
and backstepping controls.
PMID- 28688619
TI - Explicit analytical tuning rules for digital PID controllers via the magnitude
optimum criterion.
AB - Analytical tuning rules for digital PID type-I controllers are presented
regardless of the process complexity. This explicit solution allows control
engineers 1) to make an accurate examination of the effect of the controller's
sampling time to the control loop's performance both in the time and frequency
domain 2) to decide when the control has to be I, PI and when the derivative, D,
term has to be added or omitted 3) apply this control action to a series of
stable benchmark processes regardless of their complexity. The former advantages
are considered critical in industry applications, since 1) most of the times the
choice of the digital controller's sampling time is based on heuristics and past
criteria, 2) there is little a-priori knowledge of the controlled process making
the choice of the type of the controller a trial and error exercise 3) model
parameters change often depending on the control loop's operating point making in
this way, the problem of retuning the controller's parameter a much challenging
issue. Basis of the proposed control law is the principle of the PID tuning via
the Magnitude Optimum criterion. The final control law involves the controller's
sampling time Ts within the explicit solution of the controller's parameters.
Finally, the potential of the proposed method is justified by comparing its
performance with the conventional PID tuning when controlling the same process.
Further investigation regarding the choice of the controller's sampling time Ts
is also presented and useful conclusions for control engineers are derived.
PMID- 28688620
TI - Role for loss of nuclear PTEN in a harbinger of brain metastases.
AB - BACKGROUND: Earlier studies proposed phosphatase and tensin homolog (PTEN) acts
as a 3'-specific phosphatidylinositol phosphatase and inhibits the PI3K pathway.
Recent reports show that PTEN mRNA expression is significantly downregulated in
brain metastases compared to primary breast cancer. We focused on the
differential expression of nuclear and cytoplasmic PTEN between primary tumors
and brain metastases. MATERIALS AND METHODS: We retrospectively studied 30
patients with histologically confirmed primary tumors and brain metastases. PTEN
and PDK1 expression levels were examined by immunohistochemical staining and
categorized as negative, positive, or strong positive expression. The difference
in PTEN expression levels were compared, and the values with P<0.05 were
considered statistically significant. RESULTS: Expression of cytoplasmic PTEN was
100% at primary site, and 70% at brain metastases. Expression of nuclear PTEN was
87% at primary site, and 20% at brain metastases. Study results demonstrated that
PTEN expression levels in brain metastases are lower compared with that of
primary tumors. Especially, nuclear PTEN expression was significantly
downregulated in various brain metastases. Higher PDK1 expression at brain
metastases also confirmed the down regulation of PTEN function. CONCLUSIONS: Our
findings indicate that decreased PTEN function by loss of nuclear PTEN expression
may be associated with brain metastases.
PMID- 28688621
TI - Ultrasound-guided perineural injection with platelet-rich plasma improved the
neurophysiological parameters of carpal tunnel syndrome: A case report.
AB - Carpal tunnel syndrome (CTS) is a common and sometimes challenging condition,
which causes pain; paresthesia; tingling of the thumb, index and long fingers;
and even thenar weakness in the hands. The effectiveness of corticosteroid
injections seems to be transient, and there is a lack of information around long
term effects in previous studies. In recent years, platelet-rich plasma (PRP) has
proven to bean alternative as it encourages tissue regeneration. We hereby
describe a patient with CTS showing significant improvements in
electrophysiological parameters after receiving PRP injections. The results
revealed significant improvements in the distal motor and sensory latencies as
well as the sensory nerve action potential and compound muscle action potential
amplitudes of the both median nerves. In summary, if patients are refractory to
conservative treatments-such as splinting, oral medication, and corticosteroid
injection-PRP may be used as an alternative before surgical intervention.
PMID- 28688622
TI - Effects of atorvastatin on brain contusion volume and functional outcome of
patients with moderate and severe traumatic brain injury; a randomized double
blind placebo-controlled clinical trial.
AB - The aim of the current study was to investigate the effects of atorvastatin on
brain contusion volume and functional outcome of patients with moderate and
severe traumatic brain injury (TBI). The study was conducted as a randomized
clinical trial during a 16-month period from May 2015 and August 2016 in a level
I trauma center in Shiraz, Southern Iran. We included 65 patients with moderate
(GCS: 9-13) to severe (GCS: 5-8) TBI who had brain contusions of less than 30cc
volume. We excluded those who required surgical intervention. Patients were
randomly assigned to receive daily 20mg atorvastatin for 10days (n=21) or placebo
in the same dosage (n=23). The brain contusion volumetry was performed on days 0,
3 and 7 utilizing spiral thin-cut brain CT-Scan (1-mm thickness). The outcome
measured included modified Rankin scale (MRS), Glasgow Outcome Scale (GOS) and
Disability rating Scale (DRS) which were all evaluated 3months post-injury. There
was no significant difference between two study group regarding the baseline, 3rd
day and 7th day of the contusion volume and the rate of contusion expansion.
However, functional outcome scales of GOS, MRS and DRS at 3-months post-injury
were significantly better in atorvastatin arm of the study compared to placebo (p
values of 0.043, 0.039 and 0.030 respectively). Even though atorvastatin was not
found to be more effective than placebo in reducing contusion expansion rate, it
was associated with improved functional outcomes at 3-months following moderate
to severe TBI.
PMID- 28688623
TI - Neuropsychiatric debut as a presentation of Guillain-Barre Syndrome: An atypical
clinical case and literature review.
AB - INTRODUCTION: Guillain Barre Syndrome (GBS) is an acute immune-mediated
polyneuropathy most frequently presenting two to four weeks after an acute mild
moderately severe infection as progressive muscular weakness of the lower limbs
extending proximally with dysreflexia and autonomic dysfunction. While GBS is
typically believed to be isolated to the Peripheral Nervous System, Central
Nervous System (CNS) and psychiatric manifestations as a sequela of the disease
have been described in different imaging and clinical studies. Many variants of
presentation of GBS have been recognized, however a case presenting with
primarily psychiatric and autonomic dysfunction preceding muscle weakness has not
been cited in the literatures to date. CASE PRESENTATION: We describe a 24-year
old previously healthy male presenting with behavioral symptoms including
depression, anxiety, and amnesia, and autonomic dysfunction which preceded muscle
weakness by two weeks. CNS imaging and blood work results were unremarkable. GBS
was confirmed upon cerebral spinal fluid analysis remarkable for an important
cytoalbuminologic dissociation and markedly elevated protein concentration. The
patient responded well to five cycles of inpatient plasmapheresis and short-term
selective serotonin reuptake inhibitor treatment with complete recovery of both
neurological and behavioral symptoms. CONCLUSION: Though GBS is typically
considered a peripheral neuropathy, evidence for CNS involvement exists; GBS
should be considered within the differential diagnosis, and neurological features
should be monitored, in a patient with new onset unclear psychiatric and CNS
symptoms.
PMID- 28688624
TI - Indirect decompression in spinal surgery.
AB - Indirect decompression in spinal surgery means decompression of spinal nerve
tissues, such as spinal cord and nerve, without resecting the compressing tissue.
Indirect spinal decompression procedures largely can be divided into segmental
procedures and global spinal alignment procedures. Segmental procedures are
mainly performed by the distraction between two vertebrae, which lead to the
opening of the neural foramen and increases the epidural space. Such distraction
can be performed through the disc space or using posterior instrumentation.
Global spinal alignment procedures allow the spinal cord to migrate dorsally away
from areas of anterior compression. Understanding the indirect spinal
decompression procedures may broaden the options for surgical treatment and
decrease the risk of spinal nerve tissue injury.
PMID- 28688625
TI - Bilateral retrobulbar optic neuropathy as the only sign of zoledronic acid
toxicity.
AB - INTRODUCTION: Bisphosphonates may rarely cause ocular adverse effects and
retrobulbar optic neuropathy (RON) secondary to zoledronic acid is very rare.
CASE REPORT: A 67-year-old man was referred because of progressive and painless
decrease vision in the left eye. He had been treated with 7 cycles of zoledronic
acid infusions because of metastatic prostate cancer. On examination, VA was
20/20 in the right eye (OD) and 20/50 in the left eye (OS). The optic nerve was
unremarkable OU. Pattern visual evoked potentials (pVEP) and electroretinography
were performed with the result of VEP responses abolished in OS, and the VEP
waveform within the normal range amplitude and delayed peak latencies in OD. Due
to the high suspicion of bilateral RON secondary to zoledronic acid, we decided
to discontinue the treatment. Two months later, VA was 20/20 OD and hand motions
OS, with relative afferent pupillary defect and a pallor of the optic disc in OS.
The diagnosis of bilateral RON secondary to zoledronic acid infusions was
confirmed, and it was only partially reversible. DISCUSSION: Zoledronic acid is a
potent new generation bisphosphonate increasingly used in oncologic patients and
it is usually well tolerated. Optic nerve toxicity is not a side effect
recognised by either the Food and Drug Administration or the drug manufacturers,
and to our knowledge, this is the first case of zoledronic acid-related bilateral
RON with late onset. In conclusion, patients treated with bisphosphonates should
be informed about the possibility of ocular side-effects, and ophthalmologists
should be consider discontinuing the drug.
PMID- 28688626
TI - Serrated polyposis syndrome.
PMID- 28688627
TI - Human parechovirus: sepsis-like illness with pulmonary infection.
PMID- 28688628
TI - Will Mayaro virus be responsible for the next outbreak of an arthropod-borne
virus in Brazil?
AB - Mayaro virus is an alphavirus from the Togaviridae family and is transmitted
mainly by Hemagogus mosquitoes. This virus circulates in high-density tropical
forests or rural areas of Central and South America causing a disease
characterized by high-grade fever, maculopapular skin rash and marked arthralgia
that, in some patients, can persist for long periods after infection and may be
misinterpreted as chikungunya. Although only a few outbreaks involving this virus
have been reported, in the last years the number of Mayaro virus infections has
increased in the central and northern regions of Brazil. In this review, we
describe the reported prevalence of this infection over the years and discuss the
circumstances that can contribute to the establishment of an urban mayaro virus
epidemic in Brazil and the problems encountered with the specific diagnosis,
especially the antigenic cross-reactivity of this pathogen with other viruses of
the same family.
PMID- 28688629
TI - Directional analysis of cardiac motion field from gated fluorodeoxyglucose PET
images using the Discrete Helmholtz Hodge Decomposition.
AB - OBJECTIVES: Extract directional information related to left ventricular (LV)
rotation and torsion from a 4D PET motion field using the Discrete Helmholtz
Hodge Decomposition (DHHD). MATERIALS AND METHODS: Synthetic motion fields were
created using superposition of rotational and radial field components and cardiac
fields produced using optical flow from a control and patient image. These were
decomposed into curl-free (CF) and divergence-free (DF) components using the
DHHD. RESULTS: Synthetic radial components were present in the CF field and
synthetic rotational components in the DF field, with each retaining its center
position, direction of motion and diameter after decomposition. Direction of
rotation at apex and base for the control field were in opposite directions
during systole, reversing during diastole. The patient DF field had little
overall rotation with several small rotators. CONCLUSIONS: The decomposition of
the LV motion field into directional components could assist quantification of LV
torsion, but further processing stages seem necessary.
PMID- 28688630
TI - Treatment of laryngopharyngeal reflux using a sleep positioning device: A
prospective cohort study.
AB - OBJECTIVE: Laryngopharyngeal reflux (LPR) symptoms are often resistant to
management and cause significant quality of life impairment to patients with this
disease. This study assesses the utility of a sleep-positioning device (SPD) in
treating LPR. DESIGN: Single center prospective cohort study. SETTING: Tertiary
medical center PARTICIPANTS: 27 adult patients with diagnosed laryngopharyngeal
reflux. INTERVENTION: An SPD consisting of a two-component wedge-shaped base
pillow and a lateral positioning body pillow (Medcline, Amenity Health Inc.) was
given to patients with a diagnosis of LPR. Subjects slept using the device for at
least 6h per night for 28 consecutive nights. MAIN OUTCOMES: Primary outcomes
were Nocturnal Gastroesophageal Reflux Symptom Severity and Impact Questionnaire
(N-GSSIQ) and the Reflux Symptoms Index (RSI) survey instrument. Each was
collected at baseline, after 14, and after 28days of SPD use. RESULTS: 27
patients (19 female and 8 male; age 57.1+/-12.8, BMI 29.0+/-8.1) were recruited.
At baseline mean N-GSSIQ was 50.1+/-22.4 and mean RSI of 29.6+/-7.7. Repeated
measure analysis showed that subjects' total N-GSSIQ scores decreased by an
average of 19.1 (p=0.0004) points by two weeks and 26.5 points by 4weeks
(p<0.0001). RSI decreased an average of 5.3 points by 2weeks (p=0.0425) and an
average of 14.0 points by 4weeks (p<0.0001). CONCLUSIONS: In patients with LPR,
SPD treatment significantly improves self-reported symptoms of nocturnal reflux
as well as symptoms specific to LPR. These results support the therapeutic
efficacy of a SPD for patients with LPR.
PMID- 28688631
TI - Are Early Physical Activity and Sedentary Behaviors Related to Working Memory at
7 and 14 Years of Age?
AB - OBJECTIVE: To evaluate the role of extracurricular physical activity and
sedentary behavior at preschool and primary school age on working memory at
primary school age and adolescence, respectively. STUDY DESIGN: This prospective
study was based on a birth cohort across 4 Spanish regions. In the 3 younger
subcohorts (n = 1093), parents reported lifestyle habits of child at age 4 years
of age on a questionnaire, and children performed a computerized working memory
task at 7 years of age. In the older subcohort (n = 307), the questionnaire was
completed at 6 years of age and working memory was tested at 14 years of age.
Adjusted regression models were developed to investigate the associations between
lifestyle habits and working memory. RESULTS: Low extracurricular physical
activity levels at 4 years of age were associated with a nonsignificant 0.95%
(95% CI -2.81 to 0.92) reduction of correct responses in the working memory task
at age 7 years of age. Low extracurricular physical activity levels at 6 years of
age were associated with a 4.22% (95% CI -8.05 to -0.39) reduction of correct
responses at age 14 years. Television watching was not associated with working
memory. Other sedentary behaviors at 6 year of age were associated with a 5.07%
(95% CI -9.68 to -0.46) reduction of correct responses in boys at 14 years of
age. CONCLUSION: Low extracurricular physical activity levels at preschool and
primary school ages were associated with poorer working memory performance at
primary school age and adolescence, respectively. High sedentary behavior levels
at primary school age were related negatively to working memory in adolescent
boys.
PMID- 28688632
TI - ECMO Support in Lung Transplantation: A Contemporary Analysis of Hospital Charges
in the United States.
AB - BACKGROUND: There is little in the literature pertaining to cost associated with
the use of extracorporeal membrane oxygenation (ECMO) in lung transplantation. We
sought to evaluate charges associated with the index hospitalization among
recipients of a lung transplant who required ECMO to identify factors that
increase hospital charges in these patients. METHODS: With the use of the
Nationwide Inpatient Sample, we reviewed data pertaining to patients who received
a lung transplant between 2000 and 2011 and stratified them into ECMO and non
ECMO groups based on use of ECMO. Regression modeling was used to identify
differences in charges. RESULTS: Data pertaining to 15,596 recipients of a lung
transplant were evaluated, 658 (4.2%) of whom required ECMO. ECMO recipients were
more likely to have a diagnosis of idiopathic pulmonary fibrosis (3.5% versus
1.3%, p = 0.007) or pulmonary hypertension (PH) (9.1% versus 3.0%, p < 0.001).
Patients who received a bilateral lung transplant had 32.1% (95% confidence
interval [CI]: 26.2% to 37.9%, p < 0.001) higher charges. Recipients with PH had
28.7% (95% CI: 14.9% to 42.4%, p = 0.001) higher charges. Median charges for
recipients of a lung transplant who required ECMO were $780,391.50 versus
$324,279.80 for non-ECMO recipients of a lung transplant and were 50.3% (95% CI:
33.0% to 67.5%, p < 0.001) higher. Hospital charges among Medicare enrollees were
6.6% (95% CI: 0.7% to 12.5%, p = 0.028) higher than privately insured recipients
of a lung transplant. Black recipients had approximately 34.2% (95% CI: 3.2% to
65.0%, p = 0.030) higher charges. The ECMO group had longer median length of stay
(LOS) (25 versus 15 days, p < 0.001). CONCLUSIONS: Recipients of a lung
transplant who required ECMO support had longer LOS and higher hospital charges,
specifically among black recipients, recipients with PH, and Medicare enrollees.
PMID- 28688633
TI - Disease severity and treatment does not affect satisfaction in diverticulitis.
AB - BACKGROUND: Patient satisfaction is widely reported and impacts satisfaction
despite a limited understanding of the clinical and structural determinants.
Patients with diverticulitis are admitted to various services, with variable
disease severities. They, therefore, represent a unique group to delineate
relationships between these factors and satisfaction. We examined the factors
that impact hospital satisfaction in patients with diverticulitis. MATERIALS AND
METHODS: Patients admitted between 2009 and 2012 were identified using
International Classification of Diseases 9th Revision (ICD-9) codes. The primary
outcome of patient satisfaction was the Press Ganey Survey overall
hospitalization satisfaction question because of a high response rate. This is a
precursor survey to the widely available Hospital Consumer Assessment of
Healthcare Systems and Providers Survey. There was high concordance between these
items. Clinical and structural variables were collected retrospectively. Patients
were divided into two groups based on whether they gave the topbox response for
the overall hospital rating. RESULTS: Sixty-six patients were identified (56%
female, 63 +/- 14 years, length of stay: 5 +/- 5 d). Seventy-four percent
patients rated the hospitalization as topbox. Forty-four percent were admitted to
a surgical service, and 21% of all patients underwent an operation. When
comparing the topbox to the nontopbox group, demographics and disease severity
were similar. Treatment modality, admitting service, and outpatient intravenous
antibiotics did not influence patient satisfaction. CONCLUSIONS: Clinical and
structural variables did not impact overall hospital satisfaction for patients
admitted with diverticulitis. This indicates that less-tangible aspects of in
hospital care may be the primary determinants of hospital satisfaction in this
group. Efforts aimed at defining these variables are needed to improve patient
satisfaction.
PMID- 28688634
TI - Predictors of mortality in the elderly after open repair for perforated peptic
ulcer disease.
AB - BACKGROUND: As the U.S. population ages and the number of emergent surgical
repairs for perforated peptic ulcer disease (PUD) rise, contemporary national
data evaluating operative outcomes for open surgical repair for perforated PUD
among the elderly are lacking. MATERIALS AND METHODS: The National Surgical
Quality Improvement Program (2007-2014) was queried for patients >=65 y who
underwent open surgical repair for perforated PUD. The primary outcome was 30-d
mortality. Secondary outcomes included 30-d postoperative complications.
Univariate and multivariable regression analyses were performed. RESULTS:
Overall, 2131 patients underwent open surgical repair for perforated PUD. Among
those who died, more used steroids preoperatively (15% versus 9%, P = 0.001) and
fewer were independent preoperatively (55% versus 83%, P < 0.0001) compared to
those who were alive 30-d postoperatively. Common postoperative complications
were septic shock (15%) and pneumonia (12%). The overall 30-d mortality rate was
17.7%, with more deaths in subsequent decades of life (65-75 y 13% versus 75-84 y
18% versus >85 y 24%, P < 0.0001). After adjustment for other factors, mortality
was significantly associated with older age (85+ versus 65-74 y) (odds ratio
[OR], 1.5; 95% confidence interval [CI], 0.8, 1.7), dependent functional status
preoperatively ([OR], 0.2; 95% CI, 0.2, 0.3), and American Society of
Anesthesiologist classification >=4 (OR, 3.2; 95% CI, 2.4, 4.3). CONCLUSIONS: At
U.S. hospitals, open surgical repair, the accepted treatment of perforated PUD,
among the elderly is associated with significant 30-d morbidity and mortality
rates that are unacceptably high in our contemporary era. Furthermore, mortality
rates are associated with older age. Therefore, as the elderly population
continues to increase in the United States, preoperative, perioperative, and
postoperative measures must be taken to reduce this high morbidity and mortality
rates.
PMID- 28688635
TI - Melphalan hypoxic perfusion with hemofiltration for melanoma locoregional
metastases in the pelvis.
AB - BACKGROUND: For patients with melanoma metastases in the pelvic and groin
regions, the median survival time (MST) was 8 mo with old treatments, whereas
today is approximately 20 mo with new target therapy and novel immunotherapy.
Unfortunately, approximately 30% of patients are nonresponsive to these new
drugs. MATERIALS AND METHODS: Thirty-six patients, previously progressing after
standard treatments, collectively received 146 melphalan (30 mg/m2) hypoxic
pelvic perfusions with hemofiltration, in association with palliative excision in
most cases. RESULTS: The median follow-up time was 15 mo. Among 36 patients,
three patients were alive without evidence of disease after 62, 95, and 118 mo,
respectively. Thirty-three patients died of melanoma. The overall MST was 15 mo.
The 5-y survival rate was 8%. The MST was 37 mo for stage IIIB; 19 mo for stage
IIIC; and 6 mo for stage IV. The MST was 11 mo for patients with >=1 mitosis per
mm2 and 20 mo for patients with <1 mitosis per mm2; 17 mo for patients who
received excision and 7 mo for patients who did not receive excision; and 19.5 mo
for patients who received >2 treatments and 7.5 mo for patients who received <=2
treatments. CONCLUSIONS: Pelvic/inguinal perfusion is a safe and feasible
treatment for patients with advanced melanoma. Further studies are necessary to
establish if it may play a role in patients who fail current systemic therapies.
PMID- 28688636
TI - Utilization and impact of adjuvant chemotherapy among patients with resected
stage II colon cancer: a multi-institutional analysis.
AB - BACKGROUND: The use of chemotherapy among patients with stage II colon cancer is
controversial. We aimed to define the utilization and factors associated with the
receipt of chemotherapy and the impact of chemotherapy on long-term prognosis
among a large, multiinstitutional cohort of patients. MATERIALS AND METHODS: We
identified 876 patients who underwent resection for stage II colon cancer between
2004 and 2013 at one of seven participating institutions. Overall survival (OS)
and recurrence-free survival (RFS) time was calculated from the date of the index
procedure to the date of death. RESULTS: A total of 163 patients (18.6%) received
adjuvant chemotherapy and this utilization decreased over time (P = 0.003).
Younger age (P < 0.001), margin positivity (odds ratio [OR], 12.16; 95%
confidence interval [CI]: 2.57-57.52; P = 0.002), and the presence of perineural
invasion (OR, 1.24; 95% CI: 1.07-1.44; P = 0.005) increased the likelihood of
receiving chemotherapy. Receipt of chemotherapy was associated with improved
median OS and RFS. After controlling for all factors, the addition of oxaliplatin
to 5-fluorouracil did not affect survival, and there was no difference in OS
(hazard ratio [HR], 0.74; 95% CI: 0.27-2.06; P = 0.57) or RFS (HR, 0.71; 95% CI:
0.32-1.58; P = 0.88) with adjuvant treatment, including for patients with high
risk features (OS-HR, 0.63; 95% CI: 0.33-1.19; P = 0.15; RFS-HR, 0.77; 95% CI:
0.32-1.86; P = 0.56). CONCLUSIONS: The utilization of chemotherapy has declined
over time after resection for stage II colon cancer. Chemotherapy was not
independently associated with improved OS or RFS in this study group, including
in patients with high-risk features. Future prospective studies should strive to
identify the subset of stage II colon cancer patients that will benefit the most
from the addition of adjuvant chemotherapy.
PMID- 28688637
TI - Lymph node status as a prognostic factor in BRCA-positive breast cancer.
AB - BACKGROUND: The incidence of ipsilateral breast tumor recurrence (IBTR) seems to
be higher in BRCA-positive than sporadic breast cancer. We compared the oncologic
outcomes of BRCA-positive breast cancer patients managed with breast-conserving
surgery, simple mastectomy or mastectomy followed by immediate reconstruction.
MATERIALS/METHODS: Thirty four BRCA-positive breast cancers were grouped
according to surgical treatment: breast-conserving surgery (n = 17), simple
mastectomy (n = 9), and mastectomy followed by immediate reconstruction (n = 8).
Clinicopathologic factors and oncologic outcomes were compared during a 3-y mean
follow-up. RESULTS: Neoadjuvant radiotherapy and nodal and pathologic stages
differed significantly between the breast-conserving and simple mastectomy
groups. There was no oncologic event in the breast-conserving group during follow
up; however, IBTR and distant metastasis occurred in the simple mastectomy and
mastectomy followed by immediate reconstruction groups. Nodal stage was
associated with IBTR in both these groups whereas pathologic stage was associated
with distant metastasis only in the simple mastectomy group. CONCLUSIONS:
Although there were no differences in oncologic outcomes between the three
groups, the nodal stage was strongly associated with IBTR in patients with BRCA
positive breast cancer. IBTR may be attributable to nodal stage and pathologic
tumor stage.
PMID- 28688638
TI - Clinical relevance and effect of surgical wound classification in appendicitis:
Retrospective evaluation of wound classification discrepancies between surgeons,
Swissnoso-trained infection control nurse, and histology as well as surgical site
infection rates by wound class.
AB - BACKGROUND: Surgical wound classification (SWC) is used for risk stratification
of surgical site infection (SSI) and serves as the basis for measuring quality of
care. The objective was to examine the accuracy and reliability of SWC. This
study was purposed to evaluate the discrepancies in SWC as assessed by three
groups: surgeons, an infection control nurse, and histopathologic evaluation. The
secondary aim was to compare the risk-stratified SSI rates using the different
SWC methods for 30 d postoperatively. METHODS: An analysis was performed of the
appendectomies from January 2013 to June 2014 in the Cantonal Hospital of
Schaffhausen. SWC was assigned by the operating surgeon at the end of the
procedure and retrospectively reviewed by a Swissnoso-trained infection control
nurse after reading the operative and pathology report. The level of agreement
among the three different SWC assessment groups was determined using kappa
statistic. SSI rates were analyzed using a chi-square test. RESULTS: In 246
evaluated cases, the kappa scores for interrater reliability among the SWC
assessments across the three groups ranged from 0.05 to 0.2 signifying slight
agreement between the groups. SSIs were more frequently associated with trained
infection control nurse-assigned SWC than with surgeons based SWC. CONCLUSIONS:
Our study demonstrated a considerable discordance in the SWC assessments
performed by the three groups. Unfortunately, the currently practiced SWC system
suffers from ambiguity in definition and/or implementation of these definitions
is not clearly stated. This lack of reliability is problematic and may lead to
inappropriate comparisons within and between hospitals and surgeons.
PMID- 28688639
TI - Identifying preventable trauma death: does autopsy serve a role in the peer
review process?
AB - BACKGROUND: Missing life-threatening injuries is a persistent concern in any
trauma program. Autopsy is a tool routinely utilized to determine an otherwise
occult cause of death in many fields of medicine. It has been adopted as a
required component of the trauma peer review (PR) process by both the American
College of Surgeons and the Pennsylvania Trauma Foundation. We hypothesized that
autopsy would not identify preventable deaths for augmentation of the PR process.
MATERIALS AND METHODS: A retrospective chart review using our institutional
trauma registry of all trauma deaths between January 2012 and December 2015 was
performed. Per the protocol of our level 1 center, all trauma deaths are referred
to the medical examiner (ME) and reviewed as part of the trauma PR process. All
autopsy results are evaluated with relation to injury severity score (ISS),
trauma injury severity score (TRISS), nature of death, and injuries added by
autopsy. ME reports are reviewed by the trauma medical director and referred back
to the trauma PR committee if warranted. Trauma injury severity score methodology
determines the probability of survival (Ps) given injuries identified. A patient
with Ps of >=0.5 is expected to survive their injuries. Cohorts were created
based on when in the hospitalization death occurred: <24 h, or immediate death;
24 to 48 h, or early death; and death >48 h, or late death. A comparison was
conducted between the ISS and Ps calculated during trauma workup and on autopsy
using chi-square and Fischer's exact tests. RESULTS: A total of 173 patient
deaths were referred to the ME with 123 responses received. Average length of
stay was 2.61 d. Twenty-six patients had autopsy declined by the ME, 25 received
an external examination only, and 72 received a full autopsy. Autopsy identified
one case that was reconsidered in PR (P = 0.603) and added diagnoses, but not
injuries, to one patient in the early death group (P = 1) and two in the late
death group (P = 0.4921). No preventable cause of death was uncovered, and
educational use was minimal. Autopsy did identify injuries in seven cases that
were initially not consistent with expected mortality, but postmortem Ps was
consistent with expected mortality (P = 0.254). Mean ISS was 34.48, and mean Ps
was 0.275 among all patients. The most commonly identified injuries added by
autopsy were rib injuries, lung injuries, and intracranial hemorrhage.
CONCLUSIONS: Autopsy does not identify causes of preventable in an otherwise
highly functioning trauma program and may be a poor use of institutional
resources. In fact, it adds few diagnoses when death occurs after a full trauma
assessment has had time to take place. Autopsy may be of use to identify protocol
failure in maturing trauma programs, to give answers to grieving families and in
select situations where death was unanticipated even after a full evaluation took
place.
PMID- 28688640
TI - Clinical phenotypes of US level I trauma centers: use of clustering methodology.
AB - BACKGROUND: American College of Surgeons Level I Trauma Centers (ACSL1TCs) meet
the same personnel and structural requirements but serve different populations.
We hypothesized that these nuanced differences may amenable to description
through mathematical clustering methodology. METHODS: The National Trauma Data
Bank 2014 was used to derive information on ACSL1TCs. Explorative cluster
hypothesis generation was performed using Ward's linkage to determine expected
number of clusters based on patient and injury characteristics. Subsequent k
means clustering was applied for analysis. Comparison between clusters was
performed using the Kruskal-Wallis or chi-square test. RESULTS: In 2014, 113
ACSL1TCs admitted 267,808 patients (median = 2220 patients, range: 928-6643
patients). Three clusters emerged. Cluster I centers (n = 53, 47%) were more
likely to admit older, Caucasian patients who suffered from falls (P < 0.05) and
had higher proportions of private (31%) and Medicare payers (29%) (P = 0.001).
Cluster II centers (n = 18, 16%) were more likely to admit younger, minority
males who suffered from penetrating trauma (P < 0.05) and had higher proportions
of Medicaid (24%) or self-pay patients (19%) (P = 0.001). Cluster III centers (n
= 42, 37%) were similar to cluster I with respect to racial demographic and payer
status but resembled cluster II centers with respect to injury patterns (P <
0.05). CONCLUSIONS: Our analysis identified three unique, mathematically
definable clusters of ACSL1TCs serving three broadly different patient
populations. Understanding these mathematically definable clusters should have
utility when assessing an institution's financial risk profile, directing
prevention and outreach programs, and performing needs and resource assessments.
Ultimately, clustering allows for more meaningful direct comparisons between
phenotypically similar trauma centers.
PMID- 28688641
TI - Mortality after endovascular versus open repair of abdominal aortic aneurysm in
the elderly.
AB - BACKGROUND: Age is a well-known risk factor for postoperative death in patients
with abdominal aortic aneurysms (AAA), and the efficacy of open aneurysm repair
(OAR) and endovascular aneurysm repair (EVAR) remains controversial in the
elderly population. The aim of this study was to determine the predictors of 30-d
mortality after AAA repair in elderly population. METHODS: Using the National
Surgical Quality Improvement Program vascular-targeted database (2011-2014), we
identified all patients aged >70 y who underwent OAR and EVAR for nonruptured
AAA. Univariate and multivariable logistic regression analyses were implemented
to examine postoperative mortality adjusting for patient demographics and
characteristics. RESULTS: A total of 4229 nonruptured AAA repairs were performed
(OAR: 360 [8.5%] versus EVAR: 3869 [91.5%]). Most patients were males (79 %) and
White (81%) with a mean age of 78 +/- 6 y. Obesity was more prevalent in EVAR
group (31% versus 24%, P = 0.008). Whereas, smoking was more likely to be seen in
patients undergoing an OAR (35% versus 22%, P < 0.001). The 30-d mortality was
significantly higher after OAR versus EVAR (8% versus 2%, P < 0.001). After
adjusting, OAR was associated with almost five times higher mortality than EVAR
(adjusted odds ratio: 4.88; 2.85-8.34, P < 0.001). CONCLUSIONS: This study
reflects contemporary real world outcomes of nonruptured AAA repair in the
elderly. Open repair was associated with almost fivefold increase in mortality
compared with endovascular repair. Elderly patients who are functionally
dependent are less likely to benefit from AAA repair, whether OAR or EVAR.
Further prospective studies are required to better understand the predictors of
mortality after AAA repair in the geriatric population which could guide decision
making and improve outcomes in this population.
PMID- 28688642
TI - Why do patients receive care from a short-term medical mission? Survey study from
rural Guatemala.
AB - BACKGROUND: Hospital de la Familia was established to serve the indigent
population in the western highlands of Guatemala and has a full-time staff of
Guatemalan primary care providers supplemented by short-term missions of surgical
specialists. The reasons for patients seeking surgical care in this setting, as
opposed to more consistent care from local institutions, are unclear. We sought
to better understand motivations of patients seeking mission-based surgical care.
METHODS: Patients presenting to the obstetric and gynecologic, plastic,
ophthalmologic, general, and pediatric surgical clinics at the Hospital de la
Familia from July 27 to August 6, 2015 were surveyed. The surveys assessed
patient demographics, surgical diagnosis, location of home, mode of travel, and
reasons for seeking care at this facility. RESULTS: Of 252 patients surveyed, 144
(59.3%) were female. Most patients reported no other medical condition (67.9%, n
= 169) and no consistent income (83.9%, n = 209). Almost half (44.9%, n = 109)
traveled >50 km to receive care. The most common reasons for choosing care at
this facility were reputation of high quality (51.8%, n = 130) and affordability
(42.6%, n = 102); the least common reason was a lack of other options (6.4%, n =
16). CONCLUSIONS: Despite long travel distances and the availability of other
options, reputation and affordability were primarily cited as the most common
reasons for choosing to receive care at this short-term surgical mission site.
Our results highlight that although other surgical options may be closer and more
readily available, reputation and cost play a large role in choice of patients
seeking care.
PMID- 28688643
TI - Topical anesthesia for staple removal from surgical wounds on the knee: a
prospective, double-blind, randomized trial.
AB - BACKGROUND: Staple removal from surgical wounds is painful. Only a few articles
have provided expert opinions using anesthetic cream for such a problem; however,
direct application of the anesthetic cream to a wound may cause infection. A safe
alternative can be an anesthetic patch without wound contact. MATERIALS AND
METHODS: This was a prospective, double-blind, randomized clinical trial. Sixty
patients who underwent primary total knee replacement were assigned to an
experimental group or control group. One lidocaine patch was applied around the
surgical wound for each patient in the experimental group. Alternatively, the
adhesive sides of the lidocaine patches were shielded with waterproof films in
the control group. A resident peeled off the patch before a single nursing
practitioner removed the staples. Pain was assessed with the 10-cm visual analog
scale, and a face pain scale-revised was performed. The patients and the nursing
practitioner were blind to the management. RESULTS: Mean visual analog scale and
face pain scale-revised scores were significantly lower in the experimental
group. The mean pain score was significantly lower in the experimental group if
the application time was >47 min; for patients with application time of 47 min or
shorter, the score was comparable with the mean pain scores of the control group
(P = 0.215). CONCLUSIONS: Removal of the metal skin staples after total knee
arthroplasty is associated with moderate-to-severe pain. The lidocaine patch
applied topically around the surgical wound could effectively reduce the pain
during the procedure, without remarkable complications such as systemic adverse
effects or wound contamination.
PMID- 28688644
TI - A mussel-inspired double-crosslinked tissue adhesive on rat mastectomy model:
seroma prevention and in vivo biocompatibility.
AB - BACKGROUND: Seroma formation is a common postsurgical complication of breast
cancer surgery. It delays wound healing and may lead to other more serious
complications. Conventional methods of reducing seroma formation through suturing
or placement of surgical drainage produce inconsistent clinical outcomes. Tissue
adhesives are viable alternatives but most of them are unsuitable for internal
use and for large-area applications because of weak tissue adhesion strength or
biocompatibility issues. The aim of this study was to evaluate the efficacy and
biocompatibility of a mussel-inspired double-crosslinked tissue adhesive (DCTA)
in reducing seroma formation after mastectomy. MATERIALS AND METHODS: Thirty-six
female Sprague-Dawley rats were randomly assigned to either the saline control
group (n = 12), the TISSEEL sealant (Baxter) group (n = 12), or the DCTA group (n
= 12). After performing a mastectomy and applying the corresponding treatment,
the efficacy of DCTA was evaluated by measurement of seroma volume while its
biocompatibility was assessed via micronuclei test and histopathologic
examination. RESULTS: During the 1-wk postsurgical period, the average total
seroma volume of DCTA was significantly lower than the saline control group.
Importantly, the mean seroma volume in DCTA showed a decreasing trend, whereas
those in TISSEEL and saline control groups showed otherwise. The application of
DCTA showed no genotoxic effect on the host and no severe inflammation.
CONCLUSIONS: This study demonstrates that the good tissue adhesion strength and
stability of DCTA were successful in reducing seroma formation over a period of 1
wk. Furthermore, the results also showed that it is biocompatible, which makes it
suitable for large-area, internal use.
PMID- 28688645
TI - Financial benefit of a smoking cessation program prior to elective colorectal
surgery.
AB - BACKGROUND: Cigarette smoking increases the risk of postoperative complications
nearly 2-fold. Preoperative smoking cessation programs may reduce complications
as well as overall postoperative costs. We aim to create an economic evaluation
framework to estimate the potential value of preoperative smoking cessation
programs for patients undergoing elective colorectal surgery. METHODS: A decision
analytic model from the payer perspective was developed to integrate the costs
and incidence of 90-day postoperative complications and readmissions for a cohort
of patients undergoing elective colorectal surgery after a smoking cessation
program versus usual care. Complication, readmission, and cost data were derived
from a cohort of 534 current smokers and recent quitters undergoing elective
colorectal resections in Washington State's Surgical Care and Outcomes Assessment
Program linked to Washington State's Comprehensive Hospital Abstract Reporting
System. Smoking cessation program efficacy was obtained from the literature.
Sensitivity analyses were performed to account for uncertainty. RESULTS: For a
cohort of patients, the base case estimates imply that the total direct medical
costs for patients who underwent a preoperative smoking cessation program were on
average $304 (95% CI: $40-$571) lower per patient than those under usual care
during the first 90 days after surgery. The model was most sensitive to the odds
of recent quitters developing complications or requiring readmission, and smoking
program efficacy. CONCLUSIONS: A preoperative smoking cessation program is
predicted to be cost-saving over the global postoperative period if the cost of
the intervention is below $304 per patient. This framework allows the value of
smoking cessation programs of variable cost and effectiveness to be determined.
PMID- 28688646
TI - Laparoscopic versus open gastrectomy for gastric cancer with serous invasion:
long-term outcomes.
AB - BACKGROUND: Laparoscopy-assisted gastrectomy (LAG) has already been introduced
for advanced gastric cancer (AGC). However, little is known as to whether LAG is
also applicable for AGC with serous invasion given the possibility that malignant
cell dissemination and local recurrence incidence might increase. This study was
designed to evaluate the technical feasibility and oncological adequacy of LAG in
comparison with open gastrectomy (OG) for AGC with serous invasion. METHODS: A
retrospective case-matched study was conducted to compare LAG and OG for AGC with
serous invasion. For this study, 67 consecutive patients with AGC who underwent
LAG between April 2007 and March 2011 were recruited and compared with 67 AGC
patients who received OG during the same time period. We analyzed the patient
demographics, operative results, pathologic characteristics, and long-term
outcomes. RESULTS: No significant differences were observed in the numbers of
harvested lymph nodes (24.0 +/- 8.2 versus 25.6 +/- 8.8, P = 0.083) or the
average distance between the proximal and distal resection margins (4.8 +/- 2.5
cm versus 4.6 +/- 2.4 cm, P = 0.354; 6.6 +/- 4.2 cm versus 7.6 +/- 4.7 cm, P =
0.105) in the LAG and OG groups. The complication rate was similar between the
LAG and OG groups (6.0% versus 4.5%, P = 0.500). The duration of postoperative
analgesic use was significantly shorter in the LAG group than in the OG group
(2.9 +/- 0.6 d versus 3.9 +/- 0.6 d, P < 0.001). The 5-y cumulative survival and
recurrence-free survival rates of the two groups were similar (31.3% versus
29.9%, P = 0.949; 29.9% versus 23.9%, P = 0.716). CONCLUSIONS: The findings in
this study suggest that LAG is a feasible and safe procedure for patients with
seriously invasive AGC and predict acceptable long-term oncologic outcomes. LAG
may be an appropriate choice to treat patients with seriously invasive AGC.
PMID- 28688647
TI - Effect of hypothermia on splenic leukocyte modulation and survival duration in
severely septic rats.
AB - BACKGROUND: Therapeutic hypothermia (HT) in severe septic shock is associated
with prolonged survival. We hypothesized that moderate HT would prolong survival
and modulate the inflammatory response in rats with septic shock by exerting its
therapeutic effect on splenic leukocytes. MATERIALS AND METHODS: Severe septic
shock was created in rats by cecal ligation and incision (CLI). One hour after
CLI or laparotomy, rats were randomized to sham, normothermia (NT), or 4 h of HT
followed by 2 h of rewarming. HT (31 +/- 1 degrees C) was induced using a cooling
blanket and monitored via a rectal temperature probe. RESULTS: Survival duration
was 2.78 +/- 1.0 h in NT rats and 8.33 +/- 0.32 h in HT rats (n = 8/group, P <
0.0001). In separate groups, 3 h after CLI, the spleen weight was significantly
smaller in NT rats (769 +/- 100 mg) than in HT rats (947 +/- 157 mg, P = 0.04).
Fluorescent immunostaining of formyl peptide receptors on leukocytes in spleen
tissue showed considerably higher formyl peptide receptor expression in HT rats
than in NT rats. Significantly elevated proinflammatory cytokines and
myeloperoxidase enzyme in plasma were found in NT rats compared with HT rats.
Anti-inflammatory cytokine, interleukin-10, was significantly higher in HT rats.
Both proinflammatory cytokines and plasma myeloperoxidase were significantly
reduced in splenectomized NT rats. CONCLUSIONS: Moderate hypothermic therapy
significantly prolongs the survival duration of rats with severe septic shock. HT
dampens the inflammatory response during septic shock by modulating the spleen to
an anti-inflammatory mode and preventing the spleen from releasing activated
splenic leukocytes into the blood.
PMID- 28688648
TI - Nationwide review of hormonally active adrenal tumors highlights high morbidity
in pheochromocytoma.
AB - BACKGROUND: Adrenal adenomas are benign tumors often discovered incidentally, and
>70% are hormonally inactive. The remaining subset may produce excess
aldosterone, cortisol, or catecholamine. Perioperative outcomes after
adrenalectomy for such "hormonally active" tumors remain unclear. This study
examines in-hospital outcomes after unilateral adrenalectomy for hormonally
active tumors. METHODS: A retrospective review was performed using the Nationwide
Inpatient Sample (2006-2011) to identify patients undergoing unilateral
adrenalectomy for hormonally active or inactive tumors. Malignant adrenal tumors
were excluded. Demographics, comorbidities, and postoperative complications were
evaluated by univariate analysis, using two-tailed Chi-square and t-tests and
multivariate logistic regression. RESULTS: Of 27,312 patients who underwent
adrenalectomy, 78% (n = 21,279) had hormonally inactive and 22% (n = 6033) had
hormonally active adrenal tumors. Among the latter, 65% (n = 4000) had primary
hyperaldosteronism (Conn's syndrome), 33% (n = 1996) had hypercortisolism
(Cushing's syndrome), and 1.4% (n = 85) had pheochromocytoma. Patients with
pheochromocytoma had higher rate of comorbidities including congestive heart
failure, chronic lung disease, and malignant hypertension compared with remaining
hormonally active tumors (12% versus 4%, 18% versus 11%, 6% versus 2%; P < 0.01).
For patients with pheochromocytoma versus other hormonally active tumors, mean
length of stay was 5 versus 3 d and total in-hospital cost was $50,000 versus
$41,000 (P < 0.01). On multivariate analysis, pheochromocytoma had an
independently higher risk for intraoperative blood transfusion (4.2, 95%
confidence interval [CI] 2.4-7.2), postoperative cardiac (7.6, 95% CI 2.8-20.2),
and respiratory (1.9, 95% CI 1.0-3.3) complications. CONCLUSIONS: Patients with
pheochromocytoma have high rates of preoperative comorbidities, postoperative
cardiopulmonary complications, and longer and more costly hospitalizations. Such
high-risk patients should undergo appropriate preoperative medical optimization
in preparation for adrenalectomy.
PMID- 28688649
TI - Better long-term outcomes with hilar ductoplasty and a side-to-side Roux-en-Y
hepaticojejunostomy.
AB - BACKGROUND: Whether a wide hilar hepaticojejunostomy after bile duct cyst (BDC)
excision can prevent the development of postoperative complications remains an
unanswered question. We compared our outcomes after a minimum of 2-y follow-up in
patients with Todani type Ia choledochal cyst treated with hilar ductoplasty
followed by a side-to-side Roux-en-Y hepaticojejunostomy (ductoplasty group) or
radical cyst resection with an end-to-side Roux-en-Y hepaticojejunostomy
(conventional group). METHODS: We retrospectively reviewed the records of
patients with Todani type Ia choledochal cyst who received radical cyst excision
from January 1997 to December 2012, and we compared the groups' postoperative
complications and surgical outcomes. RESULTS: The groups' baseline demographics
were similar, except for age. The gender distribution and preoperative presenting
symptoms were comparable in the ductoplasty (n = 72) and conventional (n = 53)
groups (all P > 0.05). Average age was 37.0 y for the ductoplasty group and 41.8
y for the conventional group (P = 0.024). The short-term complication rate of the
groups was not significantly different (conventional group, 13.2% [7/53];
ductoplasty group, 8.3% [6/72]; all P > 0.05). A significant between-group
difference was found in the long-term complication rate of biliary-enteric
anastomotic strictures (9.4% in the conventional group and 0% in the ductoplasty
group, P = 0.012). The rates of satisfactory surgical outcomes were 91.1% and
77.1% in the ductoplasty and conventional groups, respectively (P = 0.036).
CONCLUSIONS: The application of hilar ductoplasty with a side-to-side Roux-en-Y
hepaticojejunostomy as the primary surgery for bile duct cyst excision
significantly reduced the postoperative complication of biliary-enteric
anastomotic stricture and greatly improved our patients' prognosis with regard to
biliary function.
PMID- 28688650
TI - Pilot evaluation of the Computer-Based Assessment for Sampling Personal
Characteristics test.
AB - BACKGROUND: High attrition rates hint at deficiencies in the resident selection
process. The evaluation of personal characteristics representative of success is
difficult. Here, we evaluate a novel tool for assessing personal characteristics.
MATERIALS AND METHODS: To evaluate feasibility, we used an anonymous voluntary
survey questionnaire offered to study participants before and after contact with
the CASPer test. To evaluate the CASPer test as a predictor of success, we
compared CASPer test assessments of personal characteristics versus traditional
faculty assessment of personal characteristics with applicant rank list position.
RESULTS: All applicants (n = 77) attending an in-person interview for general
surgery residency, and all faculty interviewers (n = 34) who reviewed these
applications were invited to participate. Among applicants, 84.4% of respondents
(65 of 77) reported that a requirement to complete the CASPer test would have no
bearing or would make them more likely to apply to the program (mean = 3.30,
standard deviation = 0.96). Among the faculty, 62.5% respondents (10 of 16)
reported that the same condition would have no bearing or would make applicants
more likely to apply to the program (mean = 3.19, standard deviation = 1.33). The
Spearman's rank-order correlation coefficients for the relationships between
traditional faculty assessment of personal characteristics and applicant rank
list position, and novel CASPer assessment of personal characteristics and
applicant rank list position, were -0.45 (P = 0.033) and -0.41 (P = 0.055),
respectively. CONCLUSIONS: The CASPer test may be feasibly implemented as
component of the resident selection process, with the potential to predict
applicant rank list position and improve the general surgery resident selection
process.
PMID- 28688651
TI - Feasibility and scalability of spring parameters in distraction enterogenesis in
a murine model.
AB - BACKGROUND: Distraction enterogenesis has been investigated as a novel treatment
for short bowel syndrome (SBS). With variable intestinal sizes, it is critical to
determine safe, translatable spring characteristics in differently sized animal
models before clinical use. Nitinol springs have been shown to lengthen
intestines in rats and pigs. Here, we show spring-mediated intestinal lengthening
is scalable and feasible in a murine model. MATERIALS AND METHODS: A 10-mm
nitinol spring was compressed to 3 mm and placed in a 5-mm intestinal segment
isolated from continuity in mice. A noncompressed spring placed in a similar
fashion served as a control. Spring parameters were proportionally extrapolated
from previous spring parameters to accommodate the smaller size of murine
intestines. After 2-3 wk, the intestinal segments were examined for size and
histology. RESULTS: Experimental group with spring constants, k = 0.2-1.4 N/m,
showed intestinal lengthening from 5.0 +/- 0.6 mm to 9.5 +/- 0.8 mm (P < 0.0001),
whereas control segments lengthened from 5.3 +/- 0.5 mm to 6.4 +/- 1.0 mm (P <
0.02). Diameter increased similarly in both groups. Isolated segment perforation
was noted when k >= 0.8 N/m. Histologically, lengthened segments had increased
muscularis thickness and crypt depth in comparison to normal intestine.
CONCLUSIONS: Nitinol springs with k <= 0.4 N/m can safely yield nearly 2-fold
distraction enterogenesis in length and diameter in a scalable mouse model. Not
only does this study derive the safe ranges and translatable spring
characteristics in a scalable murine model for patients with short bowel
syndrome, it also demonstrates the feasibility of spring-mediated intestinal
lengthening in a mouse, which can be used to study underlying mechanisms in the
future.
PMID- 28688652
TI - Optimal timing of cholecystectomy in children with gallstone pancreatitis.
AB - BACKGROUND: Little data exist regarding the recurrence of pancreatitis in
pediatric patients with gallstone pancreatitis awaiting cholecystectomy. This
study evaluates the recurrence rate of pancreatitis after acute gallstone
pancreatitis based on the timing of cholecystectomy in pediatric patients.
MATERIALS AND METHODS: A retrospective chart review of all patients admitted with
gallstone pancreatitis from 2007 to 2015 was performed. Children were divided
into the following five groups. Group 1 had surgery during the index admission.
Group 2 had surgery within 2 wk of discharge. Group 3 had surgery between 2 and 6
wk postdischarge. Group 4 had surgery 6 wk after discharge, and group 5 patients
had no surgery. The recurrence rates of pancreatitis were calculated for all
groups. RESULTS: Forty-eight patients with gallstone pancreatitis were identified
in this study. The 19 patients in group 1 had no recurrence of their
pancreatitis. Of the remaining 29 patients, nine (31%) had recurrence of
pancreatitis or required readmission for abdominal pain prior to their
cholecystectomy. In group 2, two of the eight patients (25%) had recurrent
pancreatitis. In group 3, three of eight patients (37.5%) developed recurrent
pancreatitis. In group 4, three of five patients (60%), and in group 5, one of
eight. No children in group 5 had demonstrable gallstones at presentation, only
sludge in their gallbladder. CONCLUSIONS: Cholecystectomy during the index
admission is associated with no recurrence or readmission for pancreatitis.
Therefore, we recommend that cholecystectomy be performed after resolution of an
episode of gallstone pancreatitis during index admission.
PMID- 28688653
TI - Ethnic disparities in traumatic brain injury care referral in a Hispanic-majority
population.
AB - BACKGROUND: Functional outcomes after traumatic brain injury (TBI) can be
significantly improved by discharge to posthospitalization care facilities. Many
variables influence the discharge disposition of the TBI patient, including
insurance status, patient condition, and patient prognosis. The literature has
demonstrated an ethnic disparity in posthospitalization care referral, with
Hispanics being discharged to rehabilitation and nursing facilities less often
than non-Hispanics. However, this relationship has not been studied in a Hispanic
majority population, and thus, this study seeks to determine if differences in
neurorehabilitation referrals exist among ethnic groups in a predominately
Hispanic region. METHODS: This study is a retrospective cohort that includes 1128
TBI patients who presented to University Medical Center El Paso, Texas, between
the years 2005 and 2015. The patients' age, sex, race, residence, admission
Glasgow Coma Scale (GCS), GCS motor, Injury Severity Score (ISS), hospital and
intensive care unit length of stay (LOS), mechanism of injury, and discharge
disposition were analyzed in univariate and multivariate models. RESULTS: Our
study population had an insurance rate of 55.5%. Insurance status and markers of
injury severity (hospital LOS, intensive care unit LOS, ISS, GCS, and GCS motor)
were predictive of discharge disposition to rehabilitation facilities. The study
population was 70% Hispanic, yet Hispanics were discharged to rehabilitation
facilities (relative risk: 0.56, P: 0.001) and to long-term acute care/nursing
facilities (relative risk: 0.35, P < 0.0001) less than non-Hispanics even after
LOS, ISS, ethnicity, insurance status, and residence were adjusted for in
multivariate analysis. CONCLUSIONS: This study suggests that patients of
different ethnicities but comparable traumatic severity and insurance status
receive different discharge dispositions post-TBI even in regions in which
Hispanics are the demographic majority.
PMID- 28688654
TI - Thyroid cancer is more likely to be detected incidentally on imaging in private
hospital patients.
AB - BACKGROUND: The incidence of well-differentiated thyroid cancer (WDTC) is
increasing. Patients with higher socioeconomic status have higher rates of WDTC,
possibly due to increased imaging and overdiagnosis. We compared methods of WDTC
diagnosis in patients treated at a public and an adjacent private university
hospital. MATERIALS AND METHODS: Patients with WDTC at the two hospitals between
2004 and 2010 were included. Patients were categorized into having their WDTC
discovered on physical examination or on unrelated imaging. Demographic and
pathologic data were collected. T-test was used for quantitative variables, and
chi-squared test was used for categorical values. Binomial logistic regression
was used to asses for confounding. RESULTS: Among 473 patients, 402 (85%) were
from the university hospital, and 71 (15%) were from the public hospital.
Patients from the university hospital were older (mean age: 49 versus 44, P =
0.02) and had a different racial composition compared to those from the public
hospital. The patients at the public hospital had larger tumors (23 versus 18 mm,
P = 0.04). Patients from the university hospital were more likely to have WDTC
detected by imaging than patients in the public hospital (46% versus 28%, P <
0.01) on univariate analysis. CONCLUSIONS: This study demonstrates that patients
with WDTC treated at a university hospital are more likely to have their tumor
detected on unrelated imaging than those treated at a public hospital. These data
may support the hypothesis that patients with improved insurance are more likely
to have WDTC detected by imaging.
PMID- 28688655
TI - Pediatric laparoscopic appendectomy, risk factors, and costs associated with
nationwide readmissions.
AB - BACKGROUND: Previous studies of readmission after pediatric laparoscopic
appendectomy have been limited to individual hospitals or noncompeting public
pediatric hospitals. The purpose of this study was to evaluate the risk factors
and costs associated with nonelective, 30-d readmissions in pediatric patients
nationwide across public and private hospitals. MATERIALS AND METHODS: The
Nationwide Readmission Database for 2013 was queried for all patients under the
age of 18 y with a diagnosis of acute appendicitis undergoing laparoscopic
appendectomy. Using multivariate logistic regression with 26 different variables,
the odds ratios (ORs) for nonelective readmissions within 30 d were determined.
The costs of readmission were calculated as well as the most common diagnoses on
readmission. RESULTS: In 2013, there were 12,730 patients under the age of 18 y
undergoing laparoscopic appendectomy, and 3.4% were readmitted within 30 d. The
overall mean age was 11.6 +/- 3.8 y, and the mean age of the readmitted patients
was 10.7 +/- 4.0 whereas the mean age of patients not readmitted was 11.6 +/- 3.8
(P < 0.01, 95% CI: 0.54-1.26). The total cost of readmissions was $3,645,502 with
a weighted nationwide estimated cost of $10,351,690. The mean readmission cost
was $8304 +/- 7864. The most common diagnosis group on readmission was
postoperative, posttraumatic, other device infections (36.0%), whereas the most
common principal diagnosis was other postoperative infection (38.5%) and the most
common secondary diagnosis was peritoneal abscess (11.9%). CONCLUSIONS:
Readmission within 30 d after laparoscopic appendectomy in pediatric patients
represents a significant resource burden. This study elucidates the patient
characteristics that predispose these patients to readmission. Efforts to reduce
these readmissions should be focused around preventing infections in patients
with these predisposing risk factors.
PMID- 28688656
TI - Notch signaling promotes ductular reactions in biliary atresia.
AB - BACKGROUND: Biliary atresia (BA) is a congenital, progressive, fibro-obliterative
disease of the extrahepatic biliary tree and the most common cause of end-stage
liver disease in children. BA is characterized by extensive intrahepatic
proliferating ductular reactions that may contribute to biliary fibrosis. Lineage
tracing during experimental cholestasis indicates that cells within ductular
reactions derive from PROM1-expressing hepatic progenitor cells. Given the role
of Notch signaling in normal biliary development, we hypothesize that activated
Notch signaling promotes the formation of ductular reactions in BA. METHODS:
Liver samples collected from BA infants at Kasai portoenterostomy and age-matched
controls, as well as from wild-type and Prom1 knockout mice with 3,5
diethoxycarbonyl-1,4-dihydrocollidine (DDC)-induced experimental cholestasis were
analyzed histologically using immunofluorescence and by quantitative polymerase
chain reaction. RESULTS: Increased expression of genes encoding Notch ligand JAG1
and its receptor NOTCH2 was observed in BA livers compared with control by
quantitative polymerase chain reaction analyses. Livers of DDC-treated mice,
which exhibit cytokeratin-19-positive ductular reactions typical of BA livers,
demonstrated significant increases in the expression level of the gene encoding
Notch2, as well as downstream Notch target gene Hes1 compared with control. Prom1
knockout mice exhibit diminished ductular reactions and decreased levels of Jag1
and Hes1 compared with littermate controls. CONCLUSIONS: Human BA and cholestasis
induced by DDC are associated with Notch signaling activation. Null mutation of
Prom1 is associated with decreased ductular reactions and decreased Notch
signaling activation during DDC treatment. These data are consistent with Notch
signaling promoting ductular reactions of Prom1 expressing progenitor cells in
BA.
PMID- 28688657
TI - Umbilical necrosis rates after abdominal-based microsurgical breast
reconstruction.
AB - BACKGROUND: Umbilical stalk necrosis represents a rare, yet important
complication after abdominal-based microsurgical breast reconstruction, which is
both underrecognized and understudied in the literature. Once identified,
umbilical reconstruction can be an extremely challenging problem. METHODS: All
consecutive breast free flaps at a single institution from February 2004 to
February 2016 were reviewed, excluding non-abdominal-based flaps. Patients were
divided based on the development of umbilical necrosis postoperatively.
Demographics, surgical characteristics, and other complications were compared
between the groups. RESULTS: A total of 918 patients met the inclusion criteria,
with 29 developing umbilical necrosis identified (3.2%). Patients developing
necrosis tended to be older (49.4 yrs versus 52.9 yrs; P < 0.01); have higher BMI
(31.3 versus 27.8; P < 0.01); and were more likely to be smokers (27.5% versus
11.6%; P = 0.01). Umbilical necrosis was also associated with increased flap
weight (830 g versus 656 g; P < 0.01), decreased time of perforator dissection
(151 min versus 169 min; P = 0.02); bilateral cases (68.9% versus 44.7%; P <
0.01), and increased number of perforators per flap (2.5 versus 2.2; P = 0.03).
There was no association with flap type (deep inferior epigastric perforator,
superficial inferior epigastric artery, or free TRAM), diabetes, previous
abdominal surgery, or use of preoperative imaging. Umbilical necrosis was not
associated with any concomitant complications. CONCLUSIONS: Umbilical stalk
necrosis was found to occur in 3.2% of patients and was associated with several
preoperative comorbidities and intraoperative characteristics. This information
should help influence intraoperative decision-making to prevent the development
of this undesirable complication.
PMID- 28688658
TI - Decreasing 30-day surgical mortality in a VA Medical Center utilizing the ACS
NSQIP Surgical Risk Calculator.
AB - BACKGROUND: The Overton Brooks VA Medical Center Surgical Service had a high
mortality. In an effort to reduce surgical mortality, we implemented a series of
quality improvement interventions, including utilization of the ACS Surgical Risk
Calculator to identify high-risk surgical patients for discussion in a
multidisciplinary Pre-Operative Consultation Committee. METHODS: Retrospective
study describing the implementation of a risk stratification intervention
incorporating the ACS Surgical Risk Calculator Tool and a multidisciplinary Pre
Operative Consultation Committee to target high-risk patients. Measurement of 30
day surgical mortality and risk adjusted Observed to Expected (O/E) mortality
ratio. RESULTS: From May 2013 to September 2014, 614 high-risk patients were
selected utilizing the ACS Risk Calculator and presented at the Pre-Operative
Consultation Committee. Following implementation of this risk stratification
intervention, 30-day mortality decreased by 66% from 0.9% to 0.3%, and risk
adjusted O/E mortality ratio decreased from 2.5 to 0.8. Among the high risk
patients presented, there was no increase in referrals to other facilities. There
was a significant increase in cases requiring further preoperative optimization,
from 6.3% at the beginning of the study period to 17.5% at the end of the study
period. CONCLUSIONS: Implementation of a preoperative risk stratification
intervention utilizing the ACS Surgical Risk Calculator along with a
multidisciplinary Pre-Operative Consultation Committee can be successfully
accomplished, with a significant decrease in 30-day surgical mortality. This is
the first published report of utilization of the ACS Risk calculator as part of a
systematic quality improvement tool to decrease surgical mortality.
PMID- 28688659
TI - Indole-3-carbinol is a potent inhibitor of ischemia-reperfusion-induced
inflammation.
AB - BACKGROUND: Ischemia-reperfusion (I/R) induces tissue inflammation, which is
characterized by an increased leukocyte-endothelial cell interaction and
leukocyte transmigration. These processes are mediated by the activation of the
nuclear factor (NF)kappaB signaling pathway, resulting in an elevated expression
of specific adhesion molecules. The phytochemical indole-3-carbinol (I3C) has
been shown to exert anti-inflammatory effects by interfering with NFkappaB signal
transduction. The aim of the present study was to investigate whether I3C is
capable of counteracting the pathogenesis of I/R injury. MATERIALS AND METHODS:
We investigated the inhibitory effect of I3C on endothelial surface protein
expression during hypoxia and reoxygenation by flow cytometry. Moreover, the
subcellular localization of NFkappaB was analyzed by immunofluorescence and
Western blot. Adhesion protein levels on leukocytes after tumor necrosis factor
alpha stimulation were determined using flow cytometry. Finally, leukocyte
endothelial cell interaction and leukocyte transmigration during I/R was
investigated in dorsal skinfold chambers of BALB/c mice by means of repetitive
intravital fluorescence microscopy and immunohistochemistry. RESULTS: I3C
suppressed the expression of E-selectin and intercellular adhesion molecule-1 on
human dermal microvascular endothelial cells by reducing the transcriptional
activity of NFkappaB. Furthermore, surface protein levels of macrophage-1 antigen
as well as activated lymphocyte function-associated antigen-1 were markedly
reduced on I3C-treated leukocytes. In vivo, I3C treatment decreased the numbers
of adherent and transmigrated leukocytes. This was associated with a reduced
macromolecular leakage when compared with vehicle-treated controls. CONCLUSIONS:
These novel results indicate that I3C reduces the expression of endothelial and
leukocytic adhesion proteins, resulting in attenuated leukocyte-endothelial cell
interactions during I/R. Accordingly, dietary supplements containing I3C may be
beneficial for the treatment of I/R-induced inflammation.
PMID- 28688661
TI - Use of axillary lymph node dissection (ALND) in patients with micrometastatic
breast cancer.
AB - BACKGROUND: Sentinel lymph node (SLN) biopsy is the current prognostic tool for
clinically node-negative breast cancer patients. If the SLN reveals
macrometastasis, axillary lymph node dissection (ALND) is recommended. However,
the use of ALND in patients with micrometastasis is debated. The objective of
this study was to assess the utilization of ALND in the treatment of
micrometastatic breast cancer. METHODS: An IRB approved, retrospective study of a
pooled dataset of breast cancer patients with micrometastatic disease on SLN
biopsy was performed. Patients diagnosed from 1999-2016 were identified via query
of a single-institution National Comprehensive Cancer Network (NCCN) breast
cancer database as well as a prospective tumor board. RESULTS: A total of 91
patients were diagnosed with micrometastatic nodal disease. The median age at
diagnosis was 56 y (range: 31-85); median follow-up time was 47 mo (range: 0-203
mo). 42/91(46.2%) patients had ALND of which 37/42 (88.1%) were a second
operation; 3/42(7.1%) patients had additional positive nodes found at ALND. 44/91
(48.4%) patients received radiation. 7/91 (7.7%) patients had a recurrence, 5/7
local, including one axillary (2.1%; patient declined ALND). CONCLUSIONS: Given
that the risk of lymphedema after ALND ranges between 20%-53%, the morbidity of
ALND may far exceed the likelihood of detecting further nodal involvement in
women with micrometastatic disease: 7.1% in this series.
PMID- 28688660
TI - Impact of tranexamic acid on coagulation and inflammation in murine models of
traumatic brain injury and hemorrhage.
AB - BACKGROUND: Posttraumatic coagulopathy and inflammation can exacerbate secondary
cerebral damage after traumatic brain injury (TBI). Tranexamic acid (TXA) has
been shown clinically to reduce mortality in hemorrhaging and head-injured trauma
patients and has the potential to mitigate secondary brain injury with its
reported antifibrinolytic and antiinflammatory properties. We hypothesized that
TXA would improve posttraumatic coagulation and inflammation in a murine model of
TBI alone and in a combined injury model of TBI and hemorrhage (TBI/H). METHODS:
An established murine weight drop model was used to induce a moderate TBI. Mice
were administered intraperitoneal injections of 10 mg/kg TXA or equivalent volume
of saline 10 min after injury. An additional group of mice was subjected to TBI
followed by hemorrhagic shock using a pressure-controlled model. TBI/H mice were
given intraperitoneal injections of TXA or saline during resuscitation. Blood was
collected at intervals after injury to assess coagulation by rotational
thromboelastometry (ROTEM) and inflammation by Multiplex cytokine analysis.
Soluble P-selectin, a biomarker of platelet activation, and serum neuron-specific
enolase, a biomarker of cerebral injury, were measured at intervals. Brain
homogenates were analyzed for inflammatory changes by Multiplex enzyme-linked
immunosorbent assay, and splenic tissue was collected for splenic cell population
assessment by flow cytometry. RESULTS: There were no coagulation, serum or
cerebral cytokine, P-selectin, or neuron-specific enolase differences between
mice treated with TXA or saline after TBI. After the addition of hemorrhagic
shock and resuscitation to TBI, TXA administration still did not affect
coagulation parameters, systemic or cerebral inflammation, or platelet
activation, as compared with saline alone. At 24 hours after TBI, mice given TXA
demonstrated lower splenic total cell counts central memory CD8, effector CD8, B
cell, and increased naive CD4 cell populations. By contrast, TXA did not affect
splenic leukocyte populations after combined TBI/H. CONCLUSIONS: Despite clinical
data suggesting a mortality benefit, TXA did not modulate coagulation,
inflammation, or biomarker generation in either the TBI or TBI/H murine models.
Administration of TXA after TBI altered splenic leukocyte populations, which may
contribute to a change in posttraumatic immune status. Future studies should be
done to investigate the role of TXA in the development of posttraumatic
immunosuppression and risk of nosocomial infections.
PMID- 28688662
TI - Improving resident well-being and clinical learning environment through academic
initiatives.
AB - BACKGROUND: Organizational effects on job satisfaction, burnout, work-life
balance, and perceived support have not been studied in the context of the
clinical learning environment. We evaluated the relationship between academic
resources and resident well-being, the clinical learning environment, and in
service examination performance of surgical residents. MATERIALS AND METHODS:
Residents of general surgery and surgical specialty programs were recruited from
March 2016 through June 2016 across the Southeast, Mid-Atlantic, and Northeast
regions. Program directors were asked to allow distribution of a paper survey or
to forward an electronic survey link onto residents. Five dichotomous questions
were asked regarding access to academic resources. Validated measures were
obtained assessing resident well-being and perceived clinical learning
environment. Data were analyzed through t-tests and chi-squared test of
independence. RESULTS: We received 276 respondents across 50 programs. Residents
perceiving adequate support to succeed had less burnout (P = 0.008), better
resilience (P = 0.009), better job satisfaction (P < 0.001), less work/life
strain (P = 0.001), better workplace climate (P < 0.001), better organizational
support (P < 0.001), and were more likely to have high performance on the in
service examination (P = 0.001). Specific resources including educational
stipends, review questions, in-service board prep, and support for poor
performers correlated with improved well-being and perceived clinical learning
environment. CONCLUSIONS: Provision of academic resources has implications beyond
in-service examination performance, correlating with improved resident well-being
and perceptions of the clinical learning environment.
PMID- 28688663
TI - Comparing traditional and novel injury scoring systems in a US level-I trauma
center: an opportunity for improved injury surveillance in low- and middle-income
countries.
AB - BACKGROUND: In most low- and middle-income countries (LMICs), the resources to
accurately quantify injury severity using traditional injury scoring systems are
limited. Novel injury scoring systems appear to have adequate discrimination for
mortality in LMIC contexts, but they have not been rigorously compared where
traditional injury scores can be accurately calculated. To determine whether
novel injury scoring systems perform as well as traditional ones in a HIC with
complete and comprehensive data collection. METHODS: Data from an American level
I trauma registry collected 2008-2013 were used to compare three traditional
injury scoring systems: Injury Severity Score (ISS); Revised Trauma Score (RTS);
and Trauma Injury Severity Score (TRISS); and three novel injury scoring systems:
Kampala Trauma Score (KTS); Mechanism, GCS, Age and Pressure (MGAP) score; and
GCS, Age and Pressure (GAP) score. Logistic regression was used to assess the
association between each scoring system and mortality. Standardized regression
coefficients (beta2), Akaike information criteria, area under the receiver
operating characteristics curve, and the calibration line intercept and slope
were used to evaluate the discrimination and calibration of each model. RESULTS:
Among 18,746 patients, all six scores were associated with hospital mortality.
GAP had the highest effect size, and KTS had the lowest median Akaike information
criteria. Although TRISS discriminated best, the discrimination of KTS approached
that of TRISS and outperformed GAP, MGAP, RTS, and ISS. MGAP was best calibrated,
and KTS was better calibrated than RTS, GAP, ISS, or TRISS. CONCLUSIONS: The
novel injury scoring systems (KTS, MGAP, and GAP), which are more feasible to
calculate in low-resource settings, discriminated hospital mortality as well as
traditional injury scoring systems (ISS and RTS) and approached the
discrimination of a sophisticated, data-intensive injury scoring system (TRISS)
in a high-resource setting. Two novel injury scoring systems (KTS and MGAP)
surpassed the calibration of TRISS. These novel injury scoring systems should be
considered when clinicians and researchers wish to accurately account for injury
severity. Implementation of these resource-appropriate tools in LMICs can improve
injury surveillance, guiding quality improvement efforts, and supporting advocacy
for resource allocation commensurate with the volume and severity of trauma.
PMID- 28688664
TI - A novel flight surgeon training model at a joint military and civilian surgical
residency program.
AB - BACKGROUND: Graduating military preliminary interns are often required to fill
flight surgeon billets. General surgery preliminary interns get experience
evaluating surgical and trauma patients, but receive very little training in
primary care and flight medicine. At a joint military and civilian training
program, we developed a supplemental curriculum to help transition our interns
into flight medicine. METHODS: From 2013 to 2016, we developed a lecture series
focused on aerospace medicine, primary care, and specialty topics including
dermatology, ophthalmology, orthopedics, pediatrics, psychiatry, and women's
health. During the 2016 iteration attended by 10 interns, pre- and post
participation 10-item Likert scale surveys were administered. Questions focused
on perceived preparedness for primary care role and overall enthusiasm for flight
medicine. Open-ended surveys from 2013 to 2016 were also used to gauge the effect
of the curriculum. RESULTS: The composite number of agreement responses
(indicating increased comfort with presented material) increased 63% after course
completion. Disagreement responses and neutral responses decreased 78% and 30%,
respectively. Open-ended surveys from 14 participants showed an overall positive
impression of the curriculum with all indicating it aided their transition to
flight medicine. CONCLUSIONS: Survey responses indicate an overall perceived
benefit from participation in the curriculum with more confidence in primary care
topics and improved transition to a flight medicine tour. This model for
supplemental aerospace medicine and primary care didactics should be integrated
into any residency program responsible for training military preliminary interns
who may serve as flight surgeons.
PMID- 28688665
TI - B cells in tertiary lymphoid structures are associated with favorable prognosis
in gastric cancer.
AB - BACKGROUND: The role of tumor-infiltrating B cells in the tumor microenvironment
is still unclear. Recent studies have reported that B cells and tertiary lymphoid
structures (TLSs) that contain B cell follicles correlate with the favorable
prognosis of cancer patients. The aim of this study was to investigate the
association between tumor-infiltrating B cells and clinicopathological features
in gastric cancer. METHODS: Tumor blocks were obtained from 226 patients with
stage Ib to stage IV gastric cancer. The density of CD20+ B cells within the
tumor and in the invasive margin area was assessed using immunohistochemistry. We
also evaluated CD3+ T cells, CD21+ follicular dendritic cells, Bcl6+ germinal
center B cells, and PNAd+ high endothelial venules to show the presence of TLSs.
RESULTS: Tumor-infiltrating B cells were mostly organized as clusters that were
surrounded by CD3+ T cells. The B cell area contained follicular dendritic cells
and some clusters contained Bcl6+ B cells. High endothelial venules were present
around follicles. We identified these follicles as TLSs. A high number of CD20+ B
cells were associated with significantly better overall survival, and
multivariate analysis also showed that CD20 high was one of the independent
predictors of prognosis. In addition, there was a significant correlation between
CD20+ B cell and CD8+ T cell infiltration. CONCLUSIONS: B cells mostly
infiltrated tumors as TLSs and were associated with better prognosis in patients
with gastric cancer.
PMID- 28688666
TI - A simple and improved method to determine cell viability in burn-injured tissue.
AB - BACKGROUND: Cell viability is paramount to wound healing in burn injury. Current
methods to determine depth of burn injury in the research setting are based on
the subjective visualization of cell viability using hematoxylin and eosin
staining. The purpose of this study was to develop a simplified method of lactate
dehydrogenase (LDH) staining to identify viable cells in frozen sections of human
burn tissue that can be used in the research setting. MATERIALS AND METHODS:
After surgical excision, human burn tissue was processed for histologic
evaluation. Tissues were fixed and protected with sucrose incubation before
cryopreservation. An LDH staining method was developed and evaluated for
prolonged stain stability. To evaluate cellular viability in the tissues as
demonstrated by enzymatic activity of LDH, digital images of tissue sections were
obtained immediately after and 1 mo after staining. RESULTS: The cryopreserved
sections of deep partial thickness human burn tissue revealed cellular viability
throughout the tissue with the exception of the most superficial region of the
tissue. Unlike the hematoxylin and eosin-stained sections, clear demarcation of
cellular viability was evident in the LDH-stained sections. CONCLUSIONS: Our
simplified protocol identifies, without ambiguity, the viability of the cellular
elements in deep partial thickness and full thickness burn injured tissue.
PMID- 28688667
TI - Clinical utility of the additional use of blue dye for indocyanine green for
sentinel node biopsy in breast cancer.
AB - BACKGROUND: Indocyanine green (ICG) is widely used as a tracer in sentinel lymph
node biopsy (SLNB) of patients with breast cancer. Whether SLNB performance can
be improved by supplementing ICG with methylene blue dye remains controversial.
This study compared the performance of SLNB when ICG was used alone or with blue
dye. MATERIALS AND METHODS: Consecutive patients with T1-3 primary breast cancer
at our hospital were recruited into our study and randomized to undergo SLNB with
ICG alone (n = 62) or with the combination of ICG and blue dye (n = 65). We
compared the two methods in terms of identification rate, number and detection
time of sentinel lymph nodes (SLNs) removed. RESULTS: SLN identification rate
were similar in the absence (95.2%) or presence of blue dye (98.5%, P = 0.578)
but significantly, more average nodes were removed when blue dye was used (3.8 +/
1.5 versus 2.7 +/- 1.2, P = 0.000), and the average time for detecting each SLN
was significantly shorter (3.91 +/- 1.87 versus 5.65 +/- 2.95 min; P = 0.000). No
patient in the study experienced severe adverse reactions or complications.
Recurrence of axillary node was detected in one patient (1.6%) using ICG alone
but not in any patients using ICG and blue dye. CONCLUSIONS: The efficiency and
sensitivity of SLNB can be improved by combining ICG with blue dye.
PMID- 28688668
TI - Infectious outcomes of gastroschisis patients with intraoperative hypothermia.
AB - BACKGROUND: Perioperative hypothermia decreases nutrient and oxygen delivery to
tissues and, in adult studies, increases the risk of infectious complications
(ICs). Gastroschisis (GS) places newborns at risk for hypothermia by nature of
exposed viscera and excessive heat loss. Although hypothermia is a known cause of
mortality in GS, the rate of ICs in this at-risk cohort has not yet been
delineated. MATERIALS AND METHODS: A retrospective cohort study was performed at
our single tertiary-referral hospital, evaluating patient and operative
characteristics of all GS infants who underwent operative closure. Intraoperative
temperatures were recorded, defining hypothermia as mild (35.5 degrees C-35.9
degrees C), moderate (35.0 degrees C-35.4 degrees C), or severe (<35 degrees C).
Temperature nadirs, procedural and anesthesia duration were observed. The primary
outcome was 30-d surgical site infections. Secondary measures included other ICs.
RESULTS: Among 43 GS neonates, 21 (48.8%) had intraoperative hypothermia,
classified as mild in 2 (4.7%), moderate in 8 (18.6%), and severe in 11 (25.6%).
Nineteen ICs occurred in 35.9% of patients, including 10 (23.3%) surgical site
infections. There was no association between hypothermia and ICs. Patient and
operative characteristics were similar between normothermic and hypothermic
groups, except that normothermic infants were more likely to have silos placed
with delayed closure than hypothermic patients (63.6% versus 23.8%, P = 0.01).
CONCLUSIONS: Infants with GS are at high risk for hypothermia and ICs, though
newborns with silos were less subject to temperature lability. A
multiinstitutional study with greater power is needed to further investigate the
relationship between perioperative hypothermia and surgical ICs.
PMID- 28688670
TI - Editorial 2017 Update.
PMID- 28688669
TI - Silver-containing dressing for surgical site infection in clean and clean
contaminated operations: a systematic review and meta-analysis of randomized
controlled trials.
AB - BACKGROUND: Silver-containing dressings for the prevention of surgical site
infections (SSIs) remained controversial, and accumulating evidence was lacking,
so a meta-analysis was conducted to systematically assess the effectiveness and
safety of silver-containing dressings for clean and clean-contaminated surgical
incisions. METHODS: Pubmed, Embase, and the Cochrane Library were searched from
the inception to February 2016 for randomized controlled trials (RCTs), which
explored silver-containing dressings for the prevention of SSIs in clean and
clean-contaminated operations. Relative risk (RR) with 95% confidence interval
(CI) was pooled using random effects model. Predefined subgroup analyses,
sensitivity analyses, and influence analyses were further undertaken. RESULTS:
Nine RCTs totaling 2196 patients (1141 in silver-containing group and 1055 in
control group) were included. Silver-containing dressings did not effectively
prevent the incidence of SSIs (9 RCTs; RR: 0.92; 95% CI: 0.66-1.29; I2 = 40%),
superficial SSIs (5 RCTs; RR: 0.67; 95% CI: 0.36-1.24; I2 = 36%), and deep SSIs
(5 RCTs; RR: 0.78; 95% CI: 0.41-1.49; I2 = 0). Subgroup analyses, sensitivity
analyses, and influence analyses confirmed the robustness of the pooled estimate.
CONCLUSIONS: The current available evidence indicated that silver-containing
dressing as compared with silver-free dressing was not associated with lower
incidence of SSIs. Considering the quality of evidence ranking very low, further
studies with higher quality should be warranted.
PMID- 28688671
TI - Mining Metagenomic Data Sets for Ancient DNA: Recommended Protocols for
Authentication.
AB - While a comparatively young area of research, investigations relying on ancient
DNA data have been highly valuable in revealing snapshots of genetic variation in
both the recent and the not-so-recent past. Born out of a tradition of single
locus PCR-based approaches that often target individual species, stringent
criteria for both data acquisition and analysis were introduced early to
establish high standards of data quality. Today, the immense volume of data made
available through next-generation sequencing has significantly increased the
analytical resolution offered by processing ancient tissues and permits parallel
analyses of host and microbial communities. The adoption of this new approach to
data acquisition, however, requires an accompanying update on methods of DNA
authentication, especially given that ancient molecules are expected to exist in
low proportions in archaeological material, where an environmental signal is
likely to dominate. In this review, we provide a summary of recent data
authentication approaches that have been successfully used to distinguish between
endogenous and nonendogenous DNA sequences in metagenomic data sets. While our
discussion mostly centers on the detection of ancient human and ancient bacterial
pathogen DNA, their applicability is far wider.
PMID- 28688672
TI - An Examination of Pre- and Posttreatment Acoustic Versus Auditory Perceptual
Analyses of Voice Across Four Common Voice Disorders.
AB - OBJECTIVE: The objective, instrumental acoustic measure of Cepstral Spectral
Index of Dysphonia (CSID) correlates with audio-perceptual measures, is sensitive
in detecting voice abnormalities, and tracks change following treatment. The
goals of the current study were to (1) test the agreement between CSID versus
auditory perceptual measures of pre- versus posttreatment voice change, and (2)
investigate whether change in scores is based on voice disorder or phonemic
structure of sentence stimuli. METHODS: Forty patients with benign voice
disorders produced sentences and a sustained /a/ vowel from the Consensus
Auditory Perceptual Evaluation of Voice protocol before and after treatment. CSID
was calculated, and overall audio-perceptual voice severity was judged by 7
blinded, trained raters using a 100-mm visual analog scale. Differences between
CSID and audio-perceptual measures of voice change across voice disorder and
stimuli, and correlation between change in CSID and perceptual rating scores were
assessed pre- and postintervention. RESULTS: Across all subjects, there were
significant correlations between CSID and perceptual ratings change scores (P <
0.001), and no significant differences in pre- and posttreatment change. Disorder
specific analyses indicated that all tested sentence/vowel contexts are effective
measures for pre- versus posttreatment change in atrophy and paralysis cases.
Acoustic versus perceptual measures of voice change were significantly correlated
in lesion cases for the sentence "How hard did he hit him" and with all sentences
combined. There were no significant findings observed for muscle tension
dysphonia. CONCLUSION: CSID provides an accurate objective correlate to auditory
perceptual posttreatment change in overall voice severity ratings. Implications
for outcomes testing and disorder-specific findings are discussed.
PMID- 28688673
TI - Characterization of pHeBE7, an IncFII-type virulence-resistance plasmid carrying
blaCTX-M-98b, blaTEM-1, and rmtB genes, detected in Escherichia coli from a
chicken isolate in China.
AB - Recently, a novel variant of the CTX-M enzyme, CTX-M-98, was detected in
Escherichia coli isolates from food animals. However, few plasmids carrying
blaCTX-M-98 have been fully characterized. In this study, we sequenced the
complete pHeBE7 plasmid, an 86,015-bp plasmid that contains the blaCTX-M-98b,
blaTEM-1, rmtB, and traT genes, using whole-genome sequencing. The backbone of
pHeBE7 shows a high similarity (>99%) to pMC-NDM, which carries the blaNDM-1
gene, however its mosaic regions remain relatively unique among sequenced
plasmids. We discovered that a typical ISEcp1-blaCTX-M-IS903 element in the
mosaic region harbors the blaCTX-M-98b gene. Conjugation and growth competition
assays indicate that pHeBE7 can be easily transmitted and that it confers a
limited fitness cost to the recipient cell. The genetic characterization of
pHeBE7 may improve our knowledge of how antibiotic resistance disseminates in
enterobacteria.
PMID- 28688674
TI - A network meta-analysis of the sequencing and types of systemic therapies with
definitive radiotherapy in locally advanced squamous cell carcinoma of the head
and neck (LASCCHN)?.
AB - OBJECTIVES: The current standard therapy for locally advanced squamous cell
carcinoma of the head and neck (LASCCHN) is platinum-based chemotherapy plus
concurrent radiotherapy (CRT), but several systemic therapies have been
evaluated. We performed a Bayesian network meta-analysis (NMA) with random
effects to enable direct and indirect comparisons of all existing treatment
modalities for LASCCHN simultaneously. MATERIAL AND METHODS: A systematic review
was conducted using MEDLINE, EMBASE, ASCO abstracts, ASTRO abstracts and the
Cochrane Central of Registered Trials using Cochrane methodology to identify
randomized controlled trials (RCTs) up to June 2016. Only abstracts that involved
the same definitive radiotherapy in the arms for the RCT were included. RESULTS:
Sixty-five RCTs involving 13,574 patients and 16 different treatment strategies
were identified. Chemotherapy plus concurrent radiation (CRT) was superior to RT
with a HR of 0.74 (95%CR 0.69-0.79) for OS in the NMA. Only 3 trials compared RT
alone to concurrent therapy with an EGFR antibody (ERT), demonstrating a superior
OS (HR 0.75, 95% CR 0.60-0.94), but this difference was not statistically
significant when interpreted in a NMA (HR 0.84, 95%CR 0.65-1.08). ERT was not
superior to CRT (HR 1.19, 95%CR 0.93-1.54), and the addition of neo-adjuvant
taxane-based chemotherapy to CRT was not beneficial (HR 0.86, 95% CR 0.70-1.07).
CONCLUSION: The addition of either adjuvant or neoadjuvant chemotherapy to the
CRT backbone does not confer an OS benefit in the treatment of LASCCHN.
Similarly, ERT does not confer an OS benefit for patients who are eligible for
CRT.
PMID- 28688675
TI - Decoding the signaling pathway initiating cellular migration in cancer
metastasis.
PMID- 28688676
TI - Predictors of readmissions after head and neck cancer surgery: A national
perspective.
AB - OBJECTIVES: Surgical oncology patients have multiple comorbidities and are at
high risk of readmission. Prior studies are limited in their ability to capture
readmissions outside of the index hospital that performed the surgery. Our goal
is to evaluate risk factors for readmission for head and neck cancer patients on
a national scale. MATERIAL AND METHODS: A retrospective cohort study of head and
neck cancer patients in the Nationwide Readmissions Database (2013). Our main
outcome was 30-day readmission. Statistical analysis included 2-sided t tests,
chi2, and multivariate logistic regression analysis. RESULTS: Within 30days,
16.1% of 11,832 patients were readmitted and 20% of readmissions were at non
index hospitals, costing $31million. Hypopharyngeal cancer patients had the
highest readmission rate (29.6%), followed by laryngeal (21.8%), oropharyngeal
(18.2%), and oral cavity (11.6%) cancers (P<0.001). Half of readmissions occurred
within 10days and were often associated with infections (27%) or wound
complications (12%). Patients from lower household income areas were more likely
to be readmitted (odds ratio [OR], 1.54; 95% confidence interval [CI], 1.16
2.05). Patients with valvular disease (OR, 2.07; 95% CI, 1.16-3.69), rheumatoid
arthritis/collagen vascular disease (OR, 2.05; 95% CI, 1.27-3.31), liver disease
(OR, 2.02, 95% CI, 1.37-2.99), and hypothyroidism (OR 1.30; 95% CI, 1.02-1.66)
were at highest risk of readmission. CONCLUSION: The true rate of 30-day
readmissions after head and neck cancer surgery is 16%, capturing non-index
hospital readmissions which make up 20% of readmissions. Readmissions after head
and neck cancer surgery are most commonly associated with infections and wound
complications.
PMID- 28688677
TI - Long-term survival of a randomized phase III trial of head and neck cancer
patients receiving concurrent chemoradiation therapy with or without low-level
laser therapy (LLLT) to prevent oral mucositis.
AB - BACKGROUND: The impact of low-level laser therapy (LLLT) to prevent oral
mucositis in patients treated with exclusive chemoradiation therapy remains
unknown. This study evaluated the overall, disease-free and progression-free
survival of these patients. METHODS: Overall, disease-free and progression-free
survival of 94 patients diagnosed with oropharynx, nasopharynx, and hypopharynx
cancer, who participated on a phase III study, was evaluated from 2007 to 2015.
The patients were subjected to conventional radiotherapy plus cisplatin every
3weeks. LLLT was applied with an InGaAlP diode (660nm-100mW-1J-4J/cm2). RESULTS:
With a median follow-up of 41.3months (range 0.7-101.9), patients receiving LLLT
had a statistically significant better complete response to treatment than those
in the placebo group (LG=89.1%; PG=67.4%; p=0.013). Patients subjected to LLLT
also displayed increase in progression-free survival than those in the placebo
group (61.7% vs. 40.4%; p=0.030; HR:1:93; CI 95%: 1.07-3.5) and had a tendency
for better overall survival (57.4% vs. 40.4%; p=0.90; HR:1.64; CI 95%: 0.92
2.91). CONCLUSION: This is the first study to suggest that LLLT may improve
survival of head and neck cancer patients treated with chemoradiotherapy. Further
studies, with a larger sample, are necessary to confirm our findings.
PMID- 28688678
TI - Partner's survivorship care needs: An analysis in head and neck cancer patients.
AB - PURPOSE: To determine the number, type and predictors of unmet needs for head and
neck cancer (HNC) survivors' partner's. METHODS: Partners of HNC patients were
invited to complete the Cancer Survivors' Partners Unmet Needs Survey (CaSPUN).
Analysis determined number, proportion and factors associated with greater unmet
needs using linear regression. Agreement between the unmet needs of patients and
their partners was determined. RESULTS: Among the 44 partners participated 29
reported >=1 unmet need and 4 had a very high number of needs (31-35). The most
common unmet needs were related to concerns about cancer returning, coping with
supporting someone with cancer, and the changes cancer has caused. The highest
reported needs were in the Relationships domain. Increasing patient unmet needs
was significantly associated with increasing partner unmet needs (p<0.01).
CONCLUSIONS: A significant proportion of head and neck cancer partners experience
unmet needs, which often differ from the patient's needs.
PMID- 28688679
TI - Long-term toxicities in 10-year survivors of radiation treatment for head and
neck cancer.
AB - OBJECTIVES: To characterize the recognized but poorly understood long-term
toxicities of radiation therapy (RT) for head and neck cancer (HNC). MATERIALS
AND METHODS: We retrospectively evaluated patients treated with curative-intent
RT for HNC between 1990 and 2005 at a single institution with systematic
multidisciplinary follow-up >=10years. Long-term toxicities of the upper
aerodigestive tract were recorded and assigned to two broad categories:
pharyngeal-laryngeal and oral cavity toxicity. Kaplan-Meier estimates and Chi
square tests were used for univariable analysis (UVA). Cox model and logistic
regression were used for multivariable analysis (MVA). RESULTS: We identified 112
patients with follow-up >=10years (median 12.2). The primary tumor sites were
pharynx (42%), oral cavity (34%), larynx (13%), and other (11%). Forty-four
percent received postoperative RT, 24% had post-RT neck dissection, and 47%
received chemotherapy. Twenty-eight (25%) patients developed pharyngeal-laryngeal
toxicity, including 23 (21%) requiring permanent G-tube placed at median of
5.6years (0-20.3) post-RT. Fifty-three (47%) developed oral cavity toxicity,
including osteoradionecrosis in 25 (22%) at a median of 7.2years (0.5-15.3) post
RT. On MVA, pharyngeal-laryngeal toxicity was significantly associated with
chemotherapy (HR 3.24, CI 1.10-9.49) and age (HR 1.04, CI 1.00-1.08); oral cavity
toxicity was significantly associated with chemotherapy (OR 4.40, CI 1.51-12.9),
oral cavity primary (OR 5.03, CI 1.57-16.1), and age (OR 0.96, CI 0.92-1.00).
CONCLUSION: Among irradiated HNC patients, pharyngeal-laryngeal and oral cavity
toxicity commonly occur years after radiation, especially in those treated with
chemotherapy. Follow-up for more than five years is essential because these
significant problems afflict patients who have been cured.
PMID- 28688680
TI - Treatment guidelines and patterns of care in oral cavity squamous cell carcinoma:
Primary surgical resection vs. nonsurgical treatment.
AB - BACKGROUND: The 2017 National Comprehensive Cancer Network Clinical Practice
Guidelines recommend surgical resection or definitive radiation therapy for early
stage oral cavity malignancies, and surgical resection or multimodality clinical
trials for late-stage disease. Few studies have been conducted to identify
predictors of choice of treatment modality for oral cavity malignancies. METHODS:
All patients in the National Cancer Data Base (NCDB) diagnosed with oral cavity
squamous cell carcinoma (OCSCC) between 1998 and 2011 were identified. Chi-square
and binary logistic regression were used to identify factors predictive of
surgical or nonsurgical treatment; multiple imputation was used for missing data.
Cox proportional hazards models were generated to identify associations between
treatment modality and overall survival (OS). RESULTS: Of 23,459 patients, 4139
(17.6%) underwent primary nonsurgical treatment. Among NCDB-registered
facilities, there has been a decrease in use of nonsurgical treatment for OCSCC
(OR 0.97, p<0.001). Older age, non-white race, Medicaid insurance, low income,
low education, and later-stage disease were associated with nonsurgical therapy,
while patients at academic/research programs were more likely to undergo surgery
(OR 0.38, p<0.001). Nonsurgical treatment was associated with decreased OS
(HR=2.02, p<0.001); this was upheld on subgroup analysis of early- and late-stage
disease. CONCLUSIONS: Use of primary nonsurgical treatment for OCSCC has
decreased over time among NCDB-registered facilities and is associated with
factors related to access to care. Surgical resection for the primary treatment
of oral cavity cancer may be associated with improved OS, though conclusions
regarding survival are limited by the non-randomized nature of the data.
PMID- 28688681
TI - The long-term oncological and functional outcomes of transoral robotic surgery in
patients with hypopharyngeal cancer.
AB - OBJECTIVE: We conducted a prospective clinical trial of transoral robotic surgery
in patients with hypopharyngeal cancer and herein report the long-term
oncological and functional outcomes. MATERIALS AND METHODS: Between April 2008
and March 2014, 45 patients diagnosed with hypopharyngeal cancer participated in
this prospective study. RESULTS: All patients were male with a mean age of
66.7years. The median follow-up period was 60months. Patients were classified
using the staging system of the American Joint Commission on Cancer, as follows:
Stage I, 7.9%; Stage II, 5.3%; Stage III, 15.8%; Stage IV, 71.1. Of all 38
patients, 17 (44.7%) were alive with no evidence of disease at the last follow
up. Seven patients (18.4%) died of TNM-related disease and fourteen (36.8%) from
other causes. The 5-year disease-specific survival rate of stage I and II
patients was 100.0%, and that of stage III and IV patients was 74.0%. The 5-year
disease-free survival rate was 100.0% for stage I and II patients and 68.6% for
stage III and IV patients. CONCLUSIONS: Patients who underwent TORS exhibited
oncological outcomes comparable to those of conventional therapies and rapid
functional recovery with low surgical morbidity. TORS and simultaneous neck
dissection, with or without adjuvant therapy, may be effective alternatives to
existing treatment methods.
PMID- 28688682
TI - Neighborhood deprivation and risk of head and neck cancer: A multilevel analysis
from France.
AB - BACKGROUND: While it is known that cancer risk is related to area-level
socioeconomic status, the extent to which these inequalities are explained by
contextual effects is poorly documented especially for head and neck cancer.
METHODS: A case-control study, ICARE, included 2415 head and neck cancer cases
and 3555 controls recruited between 2001 and 2007 from 10 French regions
retrieved from a general cancer registry. Individual socioeconomic status was
assessed using marital status, highest educational level and occupational social
class. Area-level socioeconomic status was assessed using the French version of
the European Deprivation Index (EDI). The relationship between both individual
and area-based socioeconomic level and the risk of head and neck cancer was
assessed by multilevel analyses. RESULTS: A higher risk for head and neck cancer
was found in divorced compared with married individuals (OR=2.14, 95% CI=1.78
2.57), for individuals with a basic school-leaving qualification compared with
those with higher education (OR=4.55 95% CI=3.72-5.57), for manual workers
compared with managers (OR=4.91, 95% CI=3.92-6.15) and for individuals living in
the most deprived areas compared with those living in the most affluent ones
(OR=1.98, 95% CI=1.64-2.41). The influence of area-level socioeconomic status
measured by EDI remained after controlling for individual socioeconomic
characteristics (OR=1.51; 95% confidence interval: 1.23-1.85, p-value=0.0003).
CONCLUSIONS: The role of individual socioeconomic status in the risk of head and
neck cancer is undeniable, although contextual effects of deprived areas also
increase the susceptibility of individuals developing the disease.
PMID- 28688683
TI - Predictive and prognostic value of CT based radiomics signature in locally
advanced head and neck cancers patients treated with concurrent chemoradiotherapy
or bioradiotherapy and its added value to Human Papillomavirus status.
AB - OBJECTIVES: To explore prognostic and predictive value of radiomics in patients
with locally advanced head and neck squamous cell carcinomas (LAHNSCC) treated
with concurrent chemoradiotherapy (CRT) or bioradiotherapy (BRT). MATERIALS AND
METHODS: Data of 120 patients (CRT vs. BRT matched 2:1) were retrospectively
analyzed. A total of 544 radiomics features of the primary tumor were extracted
from radiotherapy planning computed tomography scans. Cox proportional hazards
models were used to examine the association between survival and radiomics
features with false discovery rate correction. The discriminatory performance was
evaluated using receiver operating characteristic curve analysis. RESULTS:
Multivariate analysis showed a 24-feature based signature significantly predicted
for OS (HR=0.3, P=0.02) and progression-free survival (PFS) (HR=0.3, P=0.01).
Combining the radiomics signature with p16 status showed a significant
improvement of prognostic performance compared with p16 (AUC=0.78vs. AUC=0.64 at
5years, P=0.01) or radiomics signature (AUC=0.78vs. AUC=0.67, P=0.01) alone. When
patients were stratified according to this combination, OS and PFS were
significantly different according to the 4 sub-types (p16+ with low/high
signature score; p16- with low/high signature score) (P<0.001). Patients with
high signature score significantly benefited from CRT (vs. BRT) in terms of OS
(P=0.004), while no benefit from CRT in patients with low signature score.
CONCLUSION: Our analysis suggests an added value of radiomics features as
prognostic and predictive biomarker in HNSCC treated with CRT/BRT. Moreover, the
radiomics signature provided additional information to HPV/p16 status to further
stratify patients. External validation of such findings is mandatory given the
risk of overfitting.
PMID- 28688685
TI - Prognostic role of tumor infiltrating lymphocytes in EBV positive and EBV
negative nasopharyngeal carcinoma.
AB - OBJECTIVES: Tumor infiltrating lymphocytes (TILs) correlate with both better and
worse prognosis in solid tumors. As therapeutic modalities for nasopharyngeal
carcinoma (NPC) are limited, immunotherapy could be a potential alternative. Up
till now there is limited prognostic data on the role of TILs in NPC, so we
assessed the prognostic role of TILs in Epstein-Barr-virus (EBV) positive and
negative NPC. METHODS: Tissue of 92 NPCs was assessed for CD3, CD4, CD8, PD1 and
PDL1 expression in the tumor's micro-environment. Correlations between
clinicopathological characteristics was assessed using the Pearson X2 test,
Fisher's exact test and ANOVA. Survival was analyzed with the Kaplan-Meier method
and Cox regression. Differences in CD3, CD4, CD8, PD1, PDL1 counts/(co)expression
between EBV positive and negative NPCs were evaluated using the Mann-Whitney U
test. Two-tailed P values below 0.05 were considered statistically significant.
RESULTS: EBV positive NPC contains significantly more CD3, CD4 and CD8 TILs than
EBV negative NPC. In the whole NPC group, increased CD8 count is associated with
better overall survival (OS) (HR 0.219 (95%CI 0.075-0.640)), but also in cases
with PDL1 co-expression (HR 0.073 (95%CI 0.010-0.556)). In EBV positive NPC co
expression of CD8 and PDL1 showed better disease free survival (HR 0.407 (95%CI
0.195-0.850)) and OS (HR 0.170 (95%CI 0.037-0.787)). CONCLUSIONS: Although TILs
are significantly different between EBV positive and negative NPCs, it is
especially composition of the infiltrate which determines prognosis. Effects of
PD1 and CD8 need more study, because these findings show much potential in using
immunotherapeutic modalities in NPC treatment.
PMID- 28688684
TI - Early detection of squamous cell carcinoma in carcinogen induced oral cancer
rodent model by ratiometric activatable cell penetrating peptides.
AB - OBJECTIVES: Ratiometric cell-penetrating-peptides (RACPP) are hairpin-shaped
molecules that undergo cleavage by tumor-associated proteases resulting in
measurable Cy5:Cy7 fluorescence ratiometric change to label cancer in vivo. We
evaluated an MMP cleavable RACPP for use in the early detection of malignant
lesions in a carcinogen-induced rodent tumor model. METHODS: Wild-type immune
competent mice were given 4-nitroquinoline-oxide (4NQO) for 16weeks. Oral
cavities from live mice that had been intravenously administered MMP cleavable
PLGC(Me)AG-RACPP were serially imaged from week 11 through week 21 using white
light reflectance and Cy5:Cy7 ratiometric fluorescence. RESULTS: In an initial
study we found that at week 21 nearly all mice (13/14) had oral cavity lesions,
of which 90% were high-grade dysplasia or invasive carcinoma. These high-grade
lesions were identifiable with white light reflectance and RACPP Cy5:Cy7
ratiometric fluorescence with similar detectability, Area Under Curve (AUC) for
RACPP detection was 0.97 (95% Confidence interval (CI)=0.92-1.02, p<0.001),
sensitivity=89%, specificity=100%. In a follow up study, oral cavity lesions
generated by 4NQO were imaged and histologically analyzed at weeks 16, 18 and 21.
In this study we showed that RACPP-fluorescence detection positively identified
15 squamous cell carcinomas (in 6 separate mice) that were poorly visible or
undetectable by white light reflectance. CONCLUSIONS: RACPP ratiometric
fluorescence can be used to accurately detect carcinogen-induced carcinoma in
immunocompetent mice that are poorly visible or undetectable by white light
reflectance.
PMID- 28688686
TI - Hardware complications in oromandibular defects: Comparing scapular and fibular
based free flap reconstructions.
AB - BACKGROUND: Despite improvements in surgical technique and technology, hardware
complications occur relatively frequently. This study analyzes hardware
complications in patients undergoing oromandibular reconstruction using scapular
(SFF) or fibular (FFF) free flaps. METHODS: Retrospective data for 178 patients
was obtained (1999-2014) at University Hospital Network (Toronto, Canada).
Univariable and multivariable analyses were performed to identify risk factors
for hardware complications. RESULTS: Patients with FFF reconstruction (n=129) had
significantly more hardware complications than those with SFF (n=49) (16% vs.
2%;p=0.01). Surgical site infection (SSI) (OR=7.05; p<0.01), defect type
(OR=2.63; p<0.01) and flap (OR=0.12; p=0.01) were significant predictors of
hardware complications on univariable analysis. Flap type (OR=0.12; p=0.04) was
an independent predictor of plate complication after adjusting for SSI. A
subgroup analysis suggested a trend towards fewer hardware complications with SFF
stratified by mandibular defect type. CONCLUSIONS: Scapular free flaps are
associated with a lower rate of hardware-related complications in oromandibular
reconstruction.
PMID- 28688687
TI - Low skeletal muscle mass is a predictive factor for chemotherapy dose-limiting
toxicity in patients with locally advanced head and neck cancer.
AB - OBJECTIVES: Low skeletal muscle mass (SMM) or sarcopenia is emerging as an
adverse prognostic factor for chemotherapy dose-limiting toxicity (CLDT) and
survival in cancer patients. Our aim was to determine the impact of low SMM on
CDLT in patients with locally advanced head and neck squamous cell carcinoma (LA
HNSCC) treated with primary radiochemotherapy (RCT). PATIENTS AND METHODS:
Consecutive patients diagnosed with LA-HNSCC and treated with primary RCT between
2007 and 2011 in our center were included. Clinical variables were
retrospectively retrieved and SMM was measured at the level of the third cervical
vertebra using pre-treatment head and neck CT-scans. After determining a cut-off
value for low SMM, multivariate analysis was performed to identify prognostic
factors for CDLT. RESULTS: Of 112 patients included, 30.4% experienced CDLT. The
optimal cut-off value for low SMM as a predictor of CDLT was <=43.2cm2/m2. Using
this cut-off, 54.5% patients had low SMM. Patients with low SMM experienced CDLT
more frequently than patients with normal SMM (44.3% vs. 13.7%, p<0.001) and
received a higher dose of chemotherapy/kg lean body mass (estimated from SMM,
p=0.044). At multivariate analysis, low SMM was independently inversely
associated with CDLT (OR 0.93, 95%CI: 0.88-0.98). Patients experiencing CDLT had
a lower overall survival than patients who did not (mean 36.6vs. 54.2months,
p=0.038). CONCLUSION: Low SMM is an independent risk factor for CDLT in LA-HNSCC
patients treated with primary RCT. Pre-therapeutic estimation of SMM using
routine CT-scans of the head and neck region may identify patients at risk of
CDLT.
PMID- 28688688
TI - Survival after refusal of surgical treatment for locally advanced laryngeal
cancer.
AB - OBJECTIVE: Survival of advanced laryngeal cancer is declining while the
popularity of organ preservation protocols grows. This study assesses the
survival impact of refusing surgical treatment for locally advanced, resectable
laryngeal cancer. METHODS: Adult patients with T3 and T4a non-metastatic
laryngeal squamous cell carcinoma were identified from the Surveillance,
Epidemiology and End Results 18 database from 2004 to 2013. Patients were
stratified based on a recommendation for extirpative surgery and the refusal of
surgery. Multivariate logistic regression modeling identified variables
associated with refusal. A multivariate cox proportional hazard model produced
adjusted Kaplan-Meier survival curves. Survival was compared using adjusted
hazard ratios (aHR) with 95% confidence intervals (CI). RESULTS: Of 5786 patients
in the study, 2877 were recommended for surgical treatment and 138 (4.8%)
refused. Refusal of surgery was associated with unmarried status (Single, odds
ratio (OR) 1.79, CI 1.10-2.92), black race (OR 1.50, CI 1.00-2.22), T3 tumors (OR
1.80, CI 1.26-2.61) and N3 nodal disease (OR 3.50, CI 1.24-8.48). Compared to
patients undergoing surgery, those who refused had lower 5-year cancer specific
survival and increased hazard of cancer-specific mortality (aHR 1.60, CI 1.24
2.07) which resulted in decreased 5-year survival (50.0vs 60.1%), after
controlling for other factors. CONCLUSION: Refusal of surgery for locally
advanced laryngeal cancer is more common in patients without marital support and
with T3 tumors. This decision results in a 10% survival decrease at 5-year.
Future study is needed to understand patients' reasoning behind this decision and
to investigate additional factors not available in this dataset.
PMID- 28688689
TI - Characterization, treatment and outcomes of salivary ductal carcinoma using the
National Cancer Database.
AB - OBJECTIVES: To analyze clinical, treatment and outcome data for patients with
salivary ductal carcinoma in a large population-based sample. MATERIALS AND
METHODS: The National Cancer Database was queried to identify patients diagnosed
with salivary ductal carcinoma between 2004 and 2013. Kaplan Meier and Cox
regression analysis were used to assess overall survival (OS) and identify impact
of specific variables on OS. RESULTS: A total of 495 patients were identified.
The most common site of tumor origin was the parotid (80%). 130 patients (26.3%)
presented with early stage (I-II) disease, 257 patients (51.9%) with
locoregionally advanced pathologic stage (III-IVB) disease and 41 patients (8.3%)
with metastatic disease. The 5year OS for these patients was 79.5%, 40.4% and 0%
respectively. At presentation, 46.6% had node positive disease. Surgery was
performed in 100% of patients with early stage disease, 98.4% with advanced
disease and 90.2% with metastatic disease. Radiation therapy, generally
postoperative radiation, was given to 58.5% of patients with stage I-II disease,
71.6% with stage III-IVB disease and 53.7% with metastatic disease. Chemotherapy
was utilized in 5.4% of patients with stage I-II disease, 35% with stage III-IVB
and 70.7% with metastatic disease. On multivariable analysis, there were no
significant differences in OS based on receipt of adjuvant radiotherapy,
chemotherapy, or chemoradiotherapy. CONCLUSION: Salivary ductal carcinoma
represents an uncommon and aggressive subset of salivary tumors for which current
adjuvant treatments do not have a detectable impact on overall survival.
PMID- 28688690
TI - External validation of the AJCC Cancer Staging Manual, 8th edition, in an
independent cohort of oral cancer patients.
AB - OBJECTIVES: To evaluate the new American Joint Committee on Cancer (AJCC) cancer
staging manual (8th edition) in an independent cohort of patients surgically
treated for oral squamous cell carcinoma in order to determine whether the
upstaging of pT and pN classification was indicative of a worse prognosis.
METHODS: A cohort of 298 patients was analyzed retrospectively. RESULTS: Of these
patients, 22.8% received an upstaging when the depth of invasion was included
into the pT classification. Similarly, 29.2% of them were upstaged when
extracapsular extension was added to pN classification. Twenty-eight of 68
patients (41.2%) that received an upstaging of pT classification died, and 23
(33.8%) experienced disease recurrence compared to 98/229 (42.8%) and 68/229
(29.7%), respectively, for those with the same pT during follow-up. With regard
to pN classification, 70.6% of upstaged patients (60/85) died, and 50.6% (43/85)
developed recurrence of the disease compared to 63/205 (30.7%) and 42/205
(20.5%), respectively, for those with the same pN during follow-up. Patients who
were upstaged in pT classification presented a worse DFS (51.1% versus 80.4%,
P=0.007) and OS (31.5% versus 58.6%, P=0.017). Similarly, those that were
upstaged in pN classification presented a worse DFS (17.1% versus 61.2%, P=0.001)
and OS (8.5% versus 37.9%, P<0.001). CONCLUSION: The new AJCC cancer staging
manual (8th edition) allows a better stratification of oral SCC patients. By
including the depth of invasion to the pT classification and extranodal extension
to the pN classification, a worse disease-free and overall survival was assessed
for these patients.
PMID- 28688691
TI - Impact of combined modality treatment with radiotherapy and S-1 on T2N0 laryngeal
cancer: Possible improvement in survival through the prevention of second primary
cancer and distant metastasis.
AB - BACKGROUND: In patients with head and neck cancer, the management of second
primary cancer (SPC) is particularly important for improving survival because of
its high incidence and associated mortality. We evaluated the impact of
combination chemotherapy on survival and SPC. METHOD: We retrospectively analyzed
data from 49 patients treated with definitive radiation therapy (RT) for T2N0M0
laryngeal squamous cell carcinoma between 2003 and 2011. Among them, 22 patients
received combined modality treatment with radiotherapy and S-1 (RT+CT group).
RESULTS: The median follow-up period was 71months (32-111months). A significant
difference in overall survival (OS, P<0.01) was observed between the RT+CT group
(n=22) and the RT alone group (n=27) though no significant differences were
observed in local control and disease specific survival. Univariate analyses
showed that an older age (P<0.05) and a higher grade (P<0.05) were associated
with OS. Multivariate analysis identified chemotherapy as the most significant
predictor of survival (OR, 0.056; 95% CI, 0.008-0.353, P<0.01). A significantly
lower incidence of distant metastasis (DM)+SPC (5-year incidence: 5% vs. 19%,
P<0.05) and fewer deaths from these causes (1 vs. 8: P<0.05) were observed in the
RT+CT group. Multivariate analysis showed that chemotherapy was the most
significant factor for the incidence of DM+SPC (OR, 0.074; 95% CI, 0.0065-0.84;
P<0.05). CONCLUSION: The findings of this study suggest the possibility that
combined modality treatment with radiotherapy and S-1 improve survival by
preventing distant metastasis and second primary cancer.
PMID- 28688692
TI - Why are we still unable to accurately determine the malignant potential or the
behavior of oral mucosal lesions?
PMID- 28688693
TI - Very accelerated radiotherapy or concurrent chemoradiotherapy for N3 head and
neck squamous cell carcinoma: Pooled analysis of two GORTEC randomized trials.
AB - OBJECTIVE: To analyze the outcome of N3 patients treated with very accelerated
radiotherapy (VART) or different schedules of concurrent chemoradiotherapy (CRT)
within two phase III trials. PATIENTS AND METHODS: Data of 179 patients with N3
HNSCC from two GORTEC randomized trials (96-01 and 99-02) were pooled. Patients
received either VART: 64.8Gy/3.5weeks or one of the 3 following CRT regimens:
Conventional CRT: 70Gy/7weeks+3 cycles carboplatin-5FU; Moderately accelerated
CRT: 70Gy/6weeks+2 cycles carboplatin-5FU; Strongly intensified CRT:
64Gy/5weeks+cisplatin (days 2, 16, 30) and 5 FU (days 1-5, 29-33) followed by 2
cycles adjuvant cisplatin-5FU. RESULTS: Median follow-up was 13.3 and 5.2years
for GORTEC 96-01 and GORTEC 99-02, respectively. Five-year overall survival (OS)
was 13.8%. No significant difference was observed between CRT versus VART in
terms of OS (hazard ratio [HR]: 0.93, p=0.68), loco-regional progression (HR:
0.70, p=0.13), or distant progression (HR: 0.86, p=0.53). OS was worse for
patients with T3-4 tumors versus early T stage (11.0% versus 25.7%, p=0.015). In
multivariate analysis, the oropharyngeal subsite presented a higher risk of
distant metastasis (as first event 46.5% vs 19.2%, p<0.001),). A significant
interaction between treatment modalities and subsites has been observed
concerning loco-regional and distant failures. CONCLUSION: The outcome of N3
HNSCC was extremely poor despite treatment intensification and no difference
between CRT and VART. Both distant metastases and loco-regional failures remain
important treatment challenge.
PMID- 28688694
TI - Nutritional changes in patients with locally advanced head and neck cancer during
treatment.
AB - OBJECTIVE: The purpose of the study is to evaluate changes in body composition
and nutritional status that occur throughout the oncological treatment in head
and neck cancer patients. METHODS: A prospective cohort observational study in
patients diagnosed with head and neck squamous cell carcinoma (HNSCC) that
underwent treatment with induction chemotherapy (iCT) followed by
chemoradiotherapy or bioradiotherapy were invited to participate. All patients
had dietetic counseling from the diagnosis and a close monitoring throughout the
treatment implementing nutritional support as needed. RESULTS: From June 2011
until October 2012, 20 patients were included. Nutritional and anthropometric
parameters were collected at diagnosis, post iCT, after radiotherapy, 1 and
3months post radiotherapy. According to Patient Generated Subjective Global
Assessment, 30% of patients were malnourished at diagnosis. After iCT there was
an increase in weight, body mass index (BMI) and fat free mass (FFM) with almost
complete improvement in dysphagia and odynophagia. Nevertheless a significant
nutritional deterioration (p=0.0022) occurred at the end of radiotherapy with 95%
of patients becoming severe or moderate malnourished. Nutritional parameters such
as weight, BMI and hand grip strength also decrease significantly during
treatment. CONCLUSIONS: Despite an intensive nutritional support from the
diagnosis throughout the oncological treatment in advanced HNSCC cancer patients,
nutritional status deteriorates during radiotherapy. Our findings suggest that
iCT may help improve nutritional status by ameliorating the symptoms that limit
the oral intake. This improvement in the nutritional status could contribute to
minimize further deterioration. Further investigations are needed involving novel
approaches to avoid nutritional deterioration.
PMID- 28688695
TI - Transoral thyroidectomy and parathyroidectomy - A North American series of
robotic and endoscopic transoral approaches to the central neck.
AB - OBJECTIVE: Most thyroid surgery in North America is completed via a cervical
incision, which leaves a permanent scar. Approaches without cutaneous incisions
offer aesthetic advantages. This series represents the largest series of
transoral vestibular approaches to the central neck in North America, and the
first published reports of robotic transoral vestibular thyroidectomy for thyroid
carcinoma. MATERIALS AND METHODS: Data was prospectively collected for patients
that underwent transoral vestibular approach thyroidectomy and/or
parathyroidectomy between April 2016 and February 2017. RESULTS: Fifteen patients
underwent the procedure for removal of the thyroid (n=12), parathyroid (n=2) or
both thyroid and parathyroid glands (n=1). The first case was converted to an
open procedure. Fourteen were completed through these remote access incisions,
including patients with a body mass index as high as 44. There were no permanent
complications. The postoperative median Dermatology Life Quality Index score was
3, which indicates a small effect on quality of life. CONCLUSION: The transoral
vestibular approach to the central neck is a promising technique for patients who
desire to optimize aesthetics.
PMID- 28688696
TI - Prognostic value of the eighth edition AJCC TNM classification for differentiated
thyroid carcinoma.
AB - BACKGROUND: The prognostic value of the proposed eighth edition of the American
Joint Committee on Cancer (AJCC) tumor, node, and metastasis (TNM) classification
is currently unclear. The aim of the study was to evaluate the prognostic value
of the eighth edition of the AJCC TNM classification. METHODS: We retrospectively
assessed 3176 patients with differentiated thyroid carcinoma (DTC) who underwent
thyroidectomy at a tertiary Korean hospital from 1996 to 2005. Cancer-specific
survival (CSS) was analyzed using the Kaplan-Meier method and compared using the
log-rank test. Performance of the eighth edition TNM with respect to prediction
of CSS was assessed against the current seventh edition. RESULTS: Upon
reclassification according to the eighth edition, 37.6% of patients were down
staged. The proportions of stage I and II tumors increased from 61.9% to 81.1%
and from 1.7% to 16.0%, respectively, whereas those of stage III and IVB
(formerly IVC in the seventh edition) decreased from 27.6% to 2.3% and 0.8% to
0.5%, respectively. The proportions of variance explained (PVEs) for the ability
of the eighth and the seventh edition to predict CSS were 3.9% and 2.9%,
respectively. The C-index values were 0.765 (95% confidence interval 0.764-0.766)
for the eighth edition and 0.736 (0.735-0.737) for the seventh edition.
CONCLUSION: Our results demonstrate that the eighth edition TNM more accurately
predicts CSS for patients with DTC than does the seventh edition.
PMID- 28688698
TI - Prediction of distant metastases from nasopharyngeal carcinoma: Improved
diagnostic performance of MRI using nodal volume in N1 and N2 stage disease:
Methodological issues.
PMID- 28688697
TI - Dose-dependent enhancement of T-lymphocyte priming and CTL lysis following
ionizing radiation in an engineered model of oral cancer.
AB - OBJECTIVES: Determine if direct tumor cell cytotoxicity, antigen release, and
susceptibility to T-lymphocyte killing following radiation treatment is dose
dependent. MATERIALS AND METHODS: Mouse oral cancer cells were engineered to
express full-length ovalbumin as a model antigen. Tumor antigen release with
uptake and cross presentation of antigen by antigen presenting cells with
subsequent priming and expansion of antigen-specific T-lymphocytes following
radiation was modeled in vitro and in vivo. T-lymphocyte mediated killing was
measured following radiation treatment using a novel impedance-based cytotoxicity
assay. RESULTS: Radiation treatment induced dose-dependent induction of
executioner caspase activity and apoptosis in MOC1 cells. In vitro modeling of
antigen release and T-lymphocyte priming demonstrated enhanced proliferation of
OT-1 T-lymphocytes with 8Gy treatment of MOC1ova cells compared to 2Gy. This was
validated in vivo following treatment of established MOC1ova tumors and adoptive
transfer of antigen-specific T-lymphocytes. Using a novel impedance-based
cytotoxicity assay, 8Gy enhanced tumor cell susceptibility to T-lymphocyte
killing to a greater degree than 2Gy. CONCLUSION: In the context of using
clinically-relevant doses of radiation treatment as an adjuvant for
immunotherapy, 8Gy is superior to 2Gy for induction of antigen-specific immune
responses and enhancing tumor cell susceptibility to T-lymphocyte killing. These
findings have significant implications for the design of trials combining
radiation and immunotherapy.
PMID- 28688699
TI - Inflammation in the assessment of salivary cytokines in oral squamous cell
carcinoma diagnosis.
PMID- 28688701
TI - Basic and functional effects of transcranial Electrical Stimulation (tES)-An
introduction.
AB - Non-invasive brain stimulation (NIBS) has been gaining increased popularity in
human neuroscience research during the last years. Among the emerging NIBS tools
is transcranial electrical stimulation (tES), whose main modalities are
transcranial direct, and alternating current stimulation (tDCS, tACS). In tES, a
small current (usually less than 3mA) is delivered through the scalp. Depending
on its shape, density, and duration, the applied current induces acute or long
lasting effects on excitability and activity of cerebral regions, and brain
networks. tES is increasingly applied in different domains to (a) explore human
brain physiology with regard to plasticity, and brain oscillations, (b) explore
the impact of brain physiology on cognitive processes, and (c) treat clinical
symptoms in neurological and psychiatric diseases. In this review, we give a
broad overview of the main mechanisms and applications of these brain stimulation
tools.
PMID- 28688700
TI - A phase I study of cabazitaxel in combination with platinum and 5-fluorouracil
(PF) in locally advanced squamous cell carcinoma of head and neck (LA-SCCHN).
AB - BACKGROUND: There is a clinical need to improve outcomes for patients with
locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN),
especially in Human Papilloma Virus (HPV) negative and HPV positive subtypes with
a significant history of tobacco use. In animal models bearing SCCHN, Cabazitaxel
showed an excellent response rate compared to docetaxel and might prove useful in
treatment of patients. The primary objective of this study was to determine the
dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) of cabazitaxel when
combined with cisplatin and 5-fluorouracil (PF) in induction chemotherapy (IC)
for patients with SCCHN. Cabazitaxel-PF IC administered in 3 cycles (each 21
days) followed by concurrent chemoradiation (CRT) or surgery has been evaluated
to assess overall response rate (ORR) and progression-free survival (PFS) in this
population. METHODS: This phase I study employed a standard 3+3 design. DLT was
defined as grade 4 or 5 toxicity or grade 3 toxicity lasting >7days. Out of 40
consented patients with stage IV, curable, previously untreated, LA-SCHHN and
poor prognosis, 35 (32M, 3F) were enrolled and evaluated for toxicity: 19
oropharynx, 10 larynx, 2 oral cancer, 1 nasopharynx and 3 hypopharynx. Five dose
levels of cabazitaxel (10, 12.5, 15, 17.5 and 20mg/m2) were tested in combination
with cisplatin 100mg/m2 and 5-fluorouracil (5-FU) 800mg/m2/d*4days. Dose
escalation for cabazitaxel was terminated upon the occurrences of 2 DLTs and the
establishment of MTD. Cabazitaxel was then further escalated with cisplatin
75mg/m2 and 5-FU 800mg/m2/d*4days in the subsequent 3 dose levels (17.5, 20 and
22.5mg/m2). In the expansion cohort, 9 patients were enrolled at the 22.5mg/m2
dose level. Following 3 cycles of IC, patients were evaluated for clinical,
radiographic, and pathologic response to cabazitaxel-PF before beginning CRT or
surgery. RESULTS: There were two DLTs (grade 4 hyperuricemia; neutropenic fever,
sepsis, and grade 4 thrombocytopenia) among 2 patients in cohort 5 at the dose of
20mg/m2 of cabazitaxel. There were no DLTs reported with cohorts using a lower
dose of cisplatin, even in the expansion cohort. The study was stopped at the
dose of 22.5mg/m2 in accordance with the initial study design. With 33 evaluable
patients for response, the Overall Response Rate (ORR) rate was 57.6%: 9.1%
Complete Responses (CR) and 48.5% Partial Responses (PR) were noted. CONCLUSIONS:
The recommended phase II dose for cabazitaxel in combination with cisplatin
75mg/m2 and 5-FU 800mg/m2/d*4days is 22.5mg/m2 and for cisplatin 100mg/m2 and 5
FU 800mg/m2/d*4days is 17.5mg/m2. With a median follow-up of 39months, PFS for
the entire non-metastatic population at 3years was approximately 58%.
PMID- 28688702
TI - Correlates and Significance of Elevation of Cardiac Biomarkers Elevation
Following Transcatheter Aortic Valve Implantation.
AB - The Valve Academic Research Consortium-2 recommends cutoff levels of cardiac
troponin of >15 and of creatine kinase MB (CKMB) of >5 of the upper limit of
normal (ULN) as markers of periprocedural myocardial infarction. We aimed to
evaluate the correlation of these cutoffs with the survival rate in patients who
underwent transcatheter aortic valve implantation (TAVI) through the femoral
access. Patients who underwent TAVI were classified according to the
postprocedural peak marker level of >15 and >5 ULN for troponin and CKMB,
respectively. Baseline characteristics were compared, and the impact of these
markers on a 1-year survival rate was assessed. Of 474 patients who underwent
TAVI, 77% had a peak troponin level of >15 ULN, whereas only 8% had a CKMB level
of >5 ULN. Factors associated with troponin and CKMB elevations differed except
for the preserved ejection fraction, which was associated with the elevation of
both markers. Patients with troponin elevations had higher rates of postprocedure
conduction defects (p = 0.001), whereas patients with CKMB had higher rates of
bleeding (p <0.001) and stroke (p = 0.03). A troponin elevation of >15 ULN had no
impact on the 1-year survival rate (p = 0.52); however, patients with a CKMB
level of >5 ULN had increased mortality (p = 0.008), which remained significant
in the multivariate analysis (hazard ratio = 2.02, p = 0.035). Troponin level and
CKMB had a good correlation (r = 0.7), and a troponin level of 75 ULN was linked
with a CKMB level of >5 ULN. In conclusion, cardiac markers differ in their peak
levels above the ULN after TAVI. Careful attention should be taken for patients
who underwent TAVI with a CKMB level of >5 ULN, as this is the only biomarker
independently associated with survival rate.
PMID- 28688703
TI - Impact of QRS Duration on Decision of Early Removal of Pacing Catheter After
Transcatheter Aortic Valve Replacement With CoreValve Device.
AB - The purpose of this study was to determine the predictability of QRS duration
(QRSd) for temporary pacing catheter removal in patients implanted with
CoreValve. Permanent pacemaker implantation is a known complication after
transcatheter aortic valve replacement (TAVI) with CoreValve. Although post-TAVI
QRSd is highly predictive for advanced atrioventricular block (AVB), management
of delayed AVB after TAVI remains unclear. We conducted a multicentric,
prospective study of 156 consecutive patients who underwent TAVI with CoreValve
between December 2010 and January 2013. Patients who had acute AVB after TAVI
were excluded (n = 25). We classified the patients into 2 groups based on the
post-TAVI QRSd. Patients with QRSd <120 ms were assigned to early pacing catheter
removal group (n = 34), and patients with QRSd >=120 ms were assigned to keep the
pacing catheter with monitoring group (n = 97). No patient required permanent
pacemaker implantation in the early pacing catheter removal group, whereas 38
patients with QRSd >=120 ms had a delayed AVB (QRSd <120 ms vs >=120 ms: 0% vs
39%, p = 0.0001). The intensive care unit stay length, 30-day mortality, and
incidence of complications were lower in the early catheter removal group. Post
TAVI QRSd allows patient selection for early removal of pacing catheter in
patients implanted with CoreValve.
PMID- 28688704
TI - Long-Term Survival of Patients With Left Bundle Branch Block Who Are Hypo
Responders to Cardiac Resynchronization Therapy.
AB - Guidelines support cardiac resynchronization therapy with a defibrillator (CRT-D)
in mild heart failure (HF) patients with left bundle branch block (LBBB).
However, not all patients demonstrate echocardiographic or clinical response to
CRT-D. We aimed to evaluate the long-term outcomes of echocardiographic hypo
responders and clinical hypo-responders to CRT-D with LBBB in the Multicenter
Automatic Defibrillator Implantation Trial with Cardiac Resynchronization
Therapy. Five-hundred thirty-four patients with LBBB in the CRT-D arm were
followed for 5.6 years (median). Clinical hypo-response was defined as HF event
in the first year after CRT-D implantation. Echocardiographic hypo-response was
defined as <=35% reduction (median) in left ventricular end-systolic volume 1
year after CRT-D implantation without evidence of clinical hypo-response.
Echocardiographic and clinical response was observed in 257 patients (48%). Two
hundred fifty patients (47%) were echocardiographic hypo-responders and 27
patients (5%) were clinical hypo-responders. Echocardiographic hypo-responders
had increased risk of all-cause mortality compared with echocardiographic +
clinical responders (hazard ratio [HR] 2.85, 95% confidence interval [CI]: 1.37
to 5.94, p = 0.005). Clinical hypo-responders had increased risk of mortality
compared with echocardiographic + clinical responders (HR 7.49, 95% CI: 2.88 to
19.48, p <0.0001) and compared with echocardiographic hypo-responders (HR 2.63,
95% CI: 1.17 to 5.92, p = 0.020). In conclusion, during long-term follow-up,
patients with mild HF and LBBB who have echocardiographic hypo-response to CRT,
with or without clinical signs of worsening HF, have increased risk of mortality.
This study emphasizes the prognostic significance of echocardiographic assessment
of left ventricular volume after CRT implantation in LBBB patients with mild HF.
PMID- 28688706
TI - Discussion.
PMID- 28688705
TI - Density functional theory study of adsorption geometries and electronic
structures of azo-dye-based molecules on anatase TiO2 surface for dye-sensitized
solar cell applications.
AB - Structural and electronic properties of eight isolated azo dyes (ArNNAr', where
Ar and Ar' denote the aryl groups containing benzene and naphthalene skeletons,
respectively) were investigated by density functional theory (DFT) based on the
B3LYP/6-31G(d,p) and TD-B3LYP/6-311G(d,p) methods The effect of methanol solvent
on the structural and electronic properties of the azo dyes was elucidated by
employing a polarizable continuum model (PCM). Then, the azo dyes adsorbed onto
the anatase TiO2 (101) slab surface through a carboxyl group. The geometries and
electronic structures of the adsorption complexes were determined using periodic
DFT based on the PWC/DNP method. The calculated adsorption energies indicate that
the adsorbed dyes preferentially take configuration of the bidentate bridging
rather than chelating or monodentate ester-type geometries. Furthermore, the azo
compounds having two carboxyl groups are coordinated to the TiO2 surface more
preferentially through the carboxyl group connecting to the benzene skeleton than
through that connecting to the naphthalene skeleton. The dihedral angles (PhiB-N)
between the benzene- and naphthalene-skeleton moieties are smaller than 10
degrees for the adsorbed azo compounds containing one carboxyl group. In
contrast, PhiB-N>30 degrees are obtained for the adsorbed azo compounds
containing two carboxyl groups. The almost planar conformations of the former
appear to strengthen both pi-electrons conjugation and electronic coupling
between low-lying unoccupied molecular orbitals of the azo dyes and the
conduction band of TiO2. On the other hand, such coupling is very weak for the
latter, leading to a shift of the Fermi level of TiO2 in the lower-energy
direction. The obtained results are useful to the design and synthesize novel azo
dye-based molecules that give rise to higher photovoltaic performances of the dye
sensitized solar cells.
PMID- 28688707
TI - Long-term follow-up of bioprosthetic aortic valve replacement in patients aged
<=60 years.
AB - OBJECTIVE: To address the long-term durability of bioprostheses used for aortic
valve replacement (AVR) in adult patients aged <=60 years at the time of surgery.
METHODS: Through a retrospective review of a prospectively collected database, we
identified 416 bioprosthetic AVRs performed between 1977 and 2013. A prospective
follow-up of valve-related and non-valve-related events was performed. RESULTS:
Follow-up was 98.5% complete (2423.1 patient-years; average, 6 +/- 5.5 years). At
15 years, overall survival was 62.1 +/- 4.4%; freedom from valve-related death
was 97.1 +/- 1.6%. There were 68 SVD events (11.9 +/- 28.8 years after surgery).
Freedom from SVD at 15 years was 48.7 +/- 5.5% for Kaplan-Meier analysis and 61.4
+/- 4.3% for competing-risks analysis. After stratification into age subgroups
(<40 years, >=40 and <50 years, and >=50 and <=60 years), we observed no
significant difference in freedom from SVD (P = .50). The average delay to SVD
was not statistically different among subgroups (P = .30). There were 57
reoperations for SVD (11.8 +/- 5.2 years after implantation). The 15 year freedom
from reoperation for SVD was 55.4 +/- 5.6% by Kaplan-Meier analysis and 67.1 +/-
4.2% by competing-risks analysis. After stratification by age, freedom from
reoperation for SVD was comparable (P = .13). Freedom from any valve-related
complication or death was 42 +/- 5% by Kaplan-Meier analysis and 54.4 +/- 4.1% by
competing-risks analysis. CONCLUSIONS: The lifetime risk of SVD is considerable
in patients aged <=60 years at the time of bioprosthesis implantation.
Nonetheless, durability remains consistent during the first decade; additional
data are required for the second decade. Patients' information is pivotal for
valve choice (competing-risks method).
PMID- 28688708
TI - Cardiac repair with pluripotent stem cell-derived cardiomyocytes: Proof of
concept but new challenges.
PMID- 28688709
TI - Damn! Starting at the bottom again!
PMID- 28688711
TI - Outcomes of octogenarians discharged from the hospital after prolonged intensive
care unit length of stay after cardiac surgery.
AB - OBJECTIVE: Octogenarians offered complex cardiac surgery frequently experience a
prolonged intensive care unit length of stay; however, minimal data exist on the
outcomes of these patients. We sought to determine the rates and predictors of 1
year noninstitutionalized survival ("functional survival") and rehospitalization
for octogenarian patients with prolonged intensive care unit length of stay after
cardiac surgery and who were discharged from hospital. METHODS: The outcomes of
discharged patients aged 80 years or more who underwent cardiac surgery with
prolonged intensive care unit length of stay (>=5 consecutive days) from January
1, 2000, to December 31, 2011, were examined retrospectively from linked clinical
and administrative provincial databases. Regression analysis was used to
determine predictors of 1-year functional survival and rehospitalization after
discharge from the hospital. RESULTS: A total of 80 of 683 (11.7%) discharged
octogenarian patients had prolonged intensive care unit length of stay.
Functional survival at 1 year was 92% and 81% for those with nonprolonged and
prolonged intensive care unit lengths of stay, respectively (P < .01). Lack of
outpatient physician visits within 30 days of discharge (hazard ratio, 5.18; P <
.01) was a significant predictor of poor 1-year functional survival. The 1-year
rehospitalization rates were 38% and 48% for those with nonprolonged and
prolonged intensive care unit lengths of stay, respectively, with 41% of all
rehospitalizations occurring within 30 days of initial discharge. A rural
residence (hazard ratio, 1.82; P < .01) and nosocomial pneumonia during patients'
operative admissions (hazard ratio, 2.74; P < .01) were associated with
rehospitalization within 30 days of discharge. CONCLUSIONS: Octogenarians with
prolonged intensive care unit length of stay have acceptable functional survival
at 1 year but have high rates of early rehospitalization. Access to health
services may influence functional survival and early rehospitalizations. These
data suggest that close follow-up of these vulnerable patients after hospital
discharge is warranted.
PMID- 28688710
TI - Stenotic false lumen as inflow of coronary aneurysm and full-metal jacket.
PMID- 28688712
TI - Cotton Osteotomy in Flatfoot Reconstruction: A Review of Consecutive Cases.
AB - The Cotton osteotomy or opening wedge medial cuneiform osteotomy is a useful
adjunctive flatfoot reconstructive procedure that is commonly performed; however,
the outcomes are rarely reported owing to the adjunctive nature of the procedure.
The Cotton procedure is relatively quick to perform and effectively corrects
forefoot varus deformity after rearfoot fusion or osteotomy to achieve a rectus
forefoot to rearfoot relationship. Proper patient selection is critical because
the preoperative findings of medial column joint instability, concomitant hallux
valgus deformity, or degenerative joint disease of the medial column might be
better treated by arthrodesis of the naviculocuneiform or first tarsometatarsal
joints. Procedure indications also include elevatus of the first ray, which can
be a primary deformity in hallux limitus or an iatrogenic deformity after base
wedge osteotomy for hallux valgus. We undertook an institutional review board
approved retrospective review of 32 consecutive patients (37 feet) who had
undergone Cotton osteotomy as a part of flatfoot reconstruction. All but 1 case
(2.7%) had radiographic evidence of graft incorporation at 10 weeks. No patient
experienced graft shifting. Three complications (8.1%) were identified, including
2 cases with neuritis (5.4%) and 1 case of delayed union (2.7%) that healed with
a bone stimulator at 6 months postoperatively. Meary's angle improved an average
of 17.75 degrees , from -17.24 degrees +/- 8.00 degrees to 0.51 degrees +/- 3.81
degrees , and this change was statistically significant (p < .01). The present
retrospective series highlights our experience with the use of the Cotton
osteotomy as an adjunctive procedure in flatfoot reconstructive surgery.
PMID- 28688713
TI - Obesity and the risk of systemic lupus erythematosus among women in the Nurses'
Health Studies.
AB - BACKGROUND: Obesity is increasingly prevalent and related to increased risk of
several autoimmune diseases, likely via generation of inflammatory adipokines.
Prior studies have not evaluated obesity in relation to systemic lupus
erythematosus (SLE) risk. We prospectively evaluated whether obesity was
associated with increased SLE risk among women in the U.S. Nurses' Health Study
cohorts. METHODS: We conducted a prospective cohort study among 238,130 women in
the Nurses' Health Studies (NHS, 1976-2012; NHSII, 1989-2013). Incident SLE was
confirmed by American College of Rheumatology 1997 criteria and validated through
medical record review. Body mass index (BMI, kg/m2) was calculated at baseline
and on biennial questionnaires. Cox proportional hazards models estimated HRs
(95% CIs) for SLE by cumulative average BMI category {18.5 to <25 [normal
(reference)], 25 to <30 (overweight), >=30 (obese)}, adjusting for potential time
varying confounders. Models were performed separately in each cohort; results
were meta-analyzed. Sensitivity analyses used simple time-varying BMI, a 4-year
lag between exposure and SLE risk window to address potential reverse causation,
and evaluated BMI at age 18 and weight change since age 18. A secondary analysis
started follow-up in both cohorts at similar calendar years when the prevalence
of obesity in the U.S. increased most dramatically [1988 (NHS)/1989 (NHSII)].
RESULTS: We identified 153 NHS incident SLE cases and 115 incident NHSII cases
during 5,602,653 person-years of follow-up. At baseline, 8.4% of women in NHS and
11.8% in NHSII were obese. Mean age at enrollment was 42.5 (SD 7.2) years in NHS
and 34.4 (SD 4.7) years in NHSII. Cumulative average obesity was significantly
associated with SLE risk in NHSII [HR = 1.85 (1.17-2.91)], but not in NHS [HR =
1.11 (0.65-1.87)] compared to normal BMI. In the meta-analysis of both cohorts,
obesity was not significantly associated with increased risk of SLE [HR = 1.46
(0.88-2.40)]. Simple time-varying BMI and lagging the exposure window by 4 years
produced similar findings to the primary analysis. In NHSII, a 4.54 kg gain
between age 18 and enrollment slightly increased SLE risk [HR = 1.09 (1.02
1.18)]. In the secondary analysis starting follow-up of both cohorts at similar
calendar years, the point estimate for obesity in NHS was higher than the primary
analysis [HR = 1.67 (0.81-3.45)]. CONCLUSION: We observed an 85% significantly
increased risk of SLE among obese compared to normal BMI women in the more recent
NHSII cohort, but no association was observed in the earlier NHS cohort. Secular
trends in obesity may account for the differences between the two birth cohorts.
PMID- 28688714
TI - Restenosis Predictors after Carotid Angioplasty and Stenting and Its Influence on
Procedure Durability, Single-Center Experience.
AB - BACKGROUND: This article reports our experience regarding in-stent restenosis in
the carotid arteries with special focus was given to angiographic morphology and
clinical predictors of in-stent restenosis. METHODS: Between July 2008 and August
2011, 245 carotid angioplasty and stenting procedures were performed in 243
patients (172 men and 71 women). Stenting for de novo stenoses was performed in
214 (87.3%) carotid arteries, and 31 (12.7%) vessels were treated because of
postsurgical restenosis. Symptomatic lesions were detected in 187 patients
(76.3%). Angiography confirmed any significant recurrent lesion detected on the
ultrasound scan. Symptomatic or significant (70%) recurrent lesions detected on
the ultrasound scan were an indication for retreatment. RESULTS: During the
follow-up period of 821 days (range: 62-1750 days), there were 10 deaths, all non
procedure related. Stent restenosis was defined as greater than 30% narrowing of
the vessel lumen diameter and could be detected in 35 (14.3%) patients.
Retreatment was indicated in 16 (6.5%) patients. Three types of restenosis were
differentiated: tandem type restenosis (n = 5 of 35); "in-stent" restenosis (n =
18 of 35); and "end-stent" restenosis (n = 12 of 35). Interventions, either
dilation alone (n = 12) or dilation with restenting (n = 4) for restenosis, were
performed with 1 procedure-related dysphasia that resolved in 30 days. Female
gender, hypercholesterolemia, peripheral vascular disease (PVD), initial
stenosis, and surgical graft were predictors of target lesion revascularization.
CONCLUSIONS: In our cohort, history of surgical endarterectomy, female gender,
hypercholesterolemia, PVD, and initial stenosis were predictors of in-stent
restenosis. Three types of restenosis were identified in our cohort.
PMID- 28688715
TI - Multiple Silent Brain Infarcts Are Associated with Severer Stroke in Patients
with First-Ever Ischemic Stroke without Advanced Leukoaraiosis.
AB - BACKGROUND: Silent brain infarct (SBI) is associated with symptomatic stroke, but
the association between SBI and acute ischemic stroke severity is uncertain. We
aimed at investigating the association between SBI number and stroke severity in
patients with first-ever ischemic stroke without advanced leukoaraiosis. METHODS:
This study included 115 patients with first-ever ischemic stroke without advanced
leukoaraiosis. National Institutes of Health Stroke Scale (NIHSS) scores were
measured. Magnetic resonance imaging (MRI) was performed to detect the acute
ischemic infarct and SBI. The location of infarct was divided into anterior and
posterior circulations. The size of infarct was divided into large (>=15 mm) and
small (<15 mm) infarctions. The number of SBIs was divided into single and
multiple (r2) subgroups. The association between SBI and the NIHSS score was
analyzed by stratification of stroke locations. The associations between SBI and
the NIHSS score and the size of the acute ischemic infarct were analyzed by
logistic regression. RESULTS: Of the 74 patients with SBI, single SBI was 30
(40.5%) and multiple SBIs were 44 (59.5%). Age (odds ratio [OR] = 1.125, P <
.001) and hypertension (OR = 3.562, P < .05) were independent risk factors for
SBI. When adjusted for all the other vascular risk factors, multiple SBIs had a
higher percentage of more than 3 NIHSS scores (OR = 3.59, 95% confidence interval
[CI]: 1.00-12.99, P = .048) and a large acute ischemic infarct (OR = 3.71, 95%
CI: 1.23-11.22, P = .020) than no SBI. CONCLUSION: Multiple SBIs have severer
neurological deficits and larger infarcts for ischemic stroke than no SBI, which
may suggest the large-artery or cardiovascular vasculopathy evolution and poor
collateral circulation in patients with multiple SBIs.
PMID- 28688716
TI - Exercise-induced GLUT4 transcription via inactivation of HDAC4/5 in mouse
skeletal muscle in an AMPKalpha2-dependent manner.
AB - Abnormal glucose metabolism induces various metabolic disorders such as insulin
resistance and type 2 diabetes. Regular exercise improved glucose uptake and
enhanced glucose oxidation by increasing GLUT4 transcription in skeletal muscle.
However, the regulatory mechanisms of GLUT4 transcription in response to exercise
are poorly understood. AMPK is a sensor of exercise and upstream kinase of class
II HDACs that act as transcriptional repressors. We used 6-week treadmill
exercise or one single-bout exercise wild type or AMPKalpha2-/- C57BL/6J mice to
explore how HDACs regulate GLUT4 transcription and the underlying molecular
mechanisms mediated by AMPK in the physiologic process of exercise. We
demonstrate that regular physical exercise significantly enhanced GLUT4
transcription by inactivating HDAC4/5 in skeletal muscle by ChIP experiment.
HDAC4 coordinately regulated with HDAC5 represses transcriptional activity of
GLUT4 promoter in C2C12 myotubes by Luciferase assay. If either HDAC4 or HDAC5 is
silenced via RNAi technology, the functional compensation by the other will
occur. In addition, a single-bout of exercise decreased HDAC4/5 activity in
skeletal muscle of wild type but not in AMPKalpha2-/- mice, suggesting an
AMPKalpha2-dependent manner. Those findings provide new insight into the
mechanisms responsible for AMPKalpha2-dependent regulation of GLUT4 transcription
after exercise.
PMID- 28688717
TI - Detection of cardiac iron overload with native magnetic resonance T1 and T2
mapping in patients with thalassemia.
AB - BACKGROUND: To investigate the diagnostic performance of native cardiac magnetic
resonance (CMR) T1 and T2 mapping for cardiac iron overload (CIO) in thalassemia
patients. METHODS: All thalassemia patients who underwent CMR were enrolled on a
clinical 1.5T scanner. Native T1 mapping with the Modified Look-Locker Inversion
recovery (MOLLI) technique, T2 mapping using a black-blood multi-echo spin-echo
technique, and conventional T2* mapping using multi-echo gradient-echo techniques
were performed. CIO was defined by a T2* of <20ms; while severe CIO was
considered as <10ms. RESULTS: A total of 200 patients were enrolled in the study
(23.9+/-14.6years old [mean+/-SD], 102 male). Among these, 8 patients (4.0%) had
CIO. Both native T1 and T2 times were significant different among patients with
no CIO, mild-to-moderate CIO, and severe CIO (1012.7+/-57.7 vs. 846.4+/-34.4 vs
601.3+/-34.6ms for T1, p<0.05; 59.6+/-6.5 vs. 48.7+/-2.5 vs. 32.8+/-1.2ms for T2,
p<0.05). The best cut-off values for detection of CIO were 887 and 52ms for T1
and T2, respectively. This yielded a sensitivity, specificity and area under the
curve (AUC) of 100%, 98.4% and 0.997 respectively for T1, in comparison to 100%,
88.8% and 0.961 respectively for T2. CONCLUSIONS: Native T1 mapping can
differentiate between severe, mild-to-moderate, and no CIO, which appears to be a
promising technique for detection and assessment of myocardial iron.
PMID- 28688718
TI - Evolution of cardiac pathology in classic Fabry disease: Progressive
cardiomyocyte enlargement leads to increased cell death and fibrosis, and
correlates with severity of ventricular hypertrophy????????.
AB - BACKGROUND: Fabry disease, an X-linked lysosomal storage disease, results from
deficient alpha-galactosidase A (alpha-GalA) activity and the systemic
accumulation of alpha-galactosyl-terminated glycosphingolipids. Two major
phenotypes, "Classic" and "Later-Onset", lead to renal failure, and/or cardiac
disease, and early demise. To date, the evolution and progression of the cardiac
pathology and resultant clinical manifestations in family members of phenotype
have not been well characterized. METHODS AND RESULTS: In a Classic family with
nine affected members (GLA mutation c.983delG), cardiac imaging, angiography, and
cardiac biopsies were performed in four males and two heterozygous females.
Tissues were examined histologically, ultrastructurally, and myocardial necrosis
and apoptosis were evaluated by in situ ligation with hairpin probes. Increasing
cardiac pathology correlated with ECG and cardiac magnetic resonance findings.
Young affected males with "pre-hypertrophy" had 18-20MUm cardiomyocyte diameters,
<30% vacuolar areas in myocytes, and normal levels of necrosis and apoptosis.
Patients with "moderate hypertrophy" (maximal wall thickness (MWT) <=16mm) had 30
35MUm cardiomyocyte diameters, ~45% vacuolar areas, and moderate levels of
necrosis and apoptosis. In contrast, the oldest male with severe hypertrophy
(MWT=21mm) had 38-40MUm cell diameters, >60% vacuolar areas, and marked necrosis
and apoptosis. CONCLUSION: Progressive gender-specific cardiac pathology and
clinical manifestations were documented in affected Classic family members.
Increasing cardiomyocyte diameter was correlated with disease severity, age, and
gender. Fibrosis was presumably caused by cell death of enlarged, substrate
engorged cardiomyocytes. These results support early enzyme therapy in Classic
males to prevent/minimize irreversible cardiac damage.
PMID- 28688719
TI - How safe are NOACs compared with phenprocoumon after pulmonary vein isolation
with the cryoballoon technique using purse-string suture closure?
AB - INTRODUCTION: The aim of this observational study was to compare the
postprocedural incidence of bleeding and thromboembolic complications associated
with novel oral anticoagulants (NOACs) with that of interrupted and continuous
phenprocoumon after pulmonary vein isolation (PVI) using a purse-string suture
(PSS) closure of the puncture site. METHODS AND RESULTS: Consecutive patients who
had undergone PVI via cryoballoon ablation were divided into the following
groups: (1) interrupted phenprocoumon with heparin bridging (n=101), (2)
continuous phenprocoumon targeting an internationally normalized ratio>2 (n=70),
and (3) NOACs without bridging that were restarted 2-4h after the procedure
(n=185). Protamine was not administered after venous closure with PSS at the end
of the procedure. The total complication rate was significantly lower in group 3
than in groups 1 and 2 (1.62% vs. 6.93% vs. 7.14%, p=0.04). The hospital costs
were lower and the hospital stay length was significantly shorter (4484+/-3742
vs. 6082+/-4044 Euro vs. 4908+/-2925, p=0.03; 1.94+/-1.67 vs. 2.70+/-1.80 vs.
2.19+/-1.30days, p<0.01). No thromboembolic event occurred. Vascular
complications were the most common complications noted (80%). The occurrence of
any complication led to a significantly longer hospital stay (5 vs. 2days,
p<0.01) and higher costs (10,052+/-6241 Euro vs. 4747+/-3447, p<0.01). The
vascular complication rate after PSS was independent of intraprocedural heparin
dosage and activated clotting time. CONCLUSIONS: NOACs have a lower complication
rate and appear to be safer in this setting than phenprocoumon. The hospital
costs and hospital stay length after PVI was significantly reduced in patients
treated with NOACs compared with phenprocoumon.
PMID- 28688720
TI - Preparation and evaluation of mesoporous silica layers on radially elongated
pillars.
AB - The present paper describes the application of a sol-gel procedure on radially
elongated pillars (REPs) using tetramethoxysilane and methyltrimethoxysilane.
After octadecylsilylation, the quality of the porous layered REP (PLREP) columns
was evaluated by in-situ determination of migration velocities and band
broadening of coumarin dyes with fluorescence microscopy in reversed-phase liquid
chromatography. Based on the increase in retention due to the sol-gel process, an
increase in accessible specific surface by a factor of 112 was observed. Argon
physisorption measurements on bulk monoliths prepared with the same method
revealed a predominant pore size of 91A. Plate heights as low as 0.4-0.8MUm (k=0
1.97) could be obtained thanks to the very low dispersion of the REP format and
to the fact that the applied silica layer was conformally and uniformly deposited
on the flow-through channels. A kinetic plot analysis demonstrated that the
studied PLREP column will deliver more theoretical plates per unit of time than a
5MUm core shell packed bed when more than 1.0*104 theoretical plates are
required.
PMID- 28688721
TI - Separation and preparation of xanthochymol and guttiferone E by high performance
liquid chromatography and high speed counter-current chromatography combined with
silver nitrate coordination reaction.
AB - Xanthochymol (XCM) and guttiferone E (GFE), a pair of pi bond benzophenone
isomers from Garcinia xanthochymus, were once reported to be difficult or
impossible to separate. The present study reports the successful separation of
these two isomers through high performance liquid chromatography (HPLC), as well
as their effective isolation using high speed counter-current chromatography
(HSCCC) based on the silver nitrate (AgNO3) coordination reaction. First, an
effective HPLC separation system was developed, achieving a successful baseline
separation with resolution of 2.0. Based on the partition coefficient (K)
resolved by HPLC, the two-phase solvent system was determined as n-hexane,
methanol and water with the uncommon volume ratio of 4:6:1. A crude extract of
Garcinia xanthochymus (0.2g) was purified by normal HSCCC and refined with AgNO3
HSCCC. Monomers of XCM and GFE were identified by HPLC, mass spectrometry (MS)
and nuclear magnetic resonance (NMR). The results demonstrate the separation and
isolation of pi bond benzophenone isomers using ordinary octadecyl silane (C18)
columns and HSCCC.
PMID- 28688722
TI - Retrospective cohort analysis of neoadjuvant treatment and survival in resectable
and borderline resectable pancreatic ductal adenocarcinoma in a high volume
referral centre.
AB - BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a deadly disease.
Neoadjuvant therapy (NA) with chemotherapy (NAC) and radiotherapy (RT) prior to
surgery provides promise. In the absence of prospective data, well annotated
clinical data from high-volume units may provide pilot data for randomised
trials. METHODS: Medical records from a tertiary hospital in Sydney, Australia,
were analysed to identify all patients with resectable or borderline resectable
PDAC. Data regarding treatment, toxicity and survival were collected. RESULTS:
Between January 1 2010 and April 1 2016, 220 sequential patients were treated: 87
with NA and 133 with upfront operation (UO). Forty-three NA patients (52%) and 5
UO patients (4%) were borderline resectable at diagnosis. Twenty-four borderline
patients received NA RT, 22 sequential to NAC. The median overall survival (OS)
in the NA group was 25.9 months (mo); 95% CI (21.1-43.0 mo) compared to 26.9 mo
(19.7, 32.7) in the UO; HR 0.89; log-ranked p-value = 0.58. Sixty-nine NA
patients (79%) were resected, mOS was 29.2 mo (22.27, not reached (NR)). Twenty
two NA (31%) versus 22 UO (17%) were node negative at operation (N0). In those
managed with NAC/RT the mOS was 29.0 mo (17.3, NR). There were no post-operative
deaths with NA within 90-days and three in the UO arm. DISCUSSION: This is a
hypothesis generating retrospective review of a selected real-world population in
a high-throughput unit. Treatment with NA was well tolerated. The long observed
survival in this group may be explained by lymph node sterilisation by NA, and
the achievement of R0 resection in a greater proportion of patients.
PMID- 28688723
TI - Focally positive margins in breast conserving surgery: Predictors, residual
disease, and local recurrence.
AB - BACKGROUND: Re-excision after breast conserving surgery (BCS) for invasive breast
cancer (IBC) can be omitted for focally positive margins in the Netherlands, but
this guideline is not routinely followed. Focally positive and extensively
positive margins have rarely been studied separately and compared to negative
margins regarding clinicopathological predictors, residual disease incidence, and
local recurrence. METHODS: All females with BCS for Tis-T3, without neo-adjuvant
chemotherapy between 2005 and 2014 at one university hospital were included.
Clinicopathological and follow-up information was collected from electronic
patient records. Index tumor samples from all patients with re-excision were
reviewed by one pathologist. Margins were classified as negative (>=2 mm width),
close (<2 mm width), focally positive (<=4 mm length of tumor touching inked
margin), or extensively positive (>4 mm length). RESULTS: From 499 patients
included, 212 (43%) had negative, 161 (32%) had close, 59 (12%) had focally
positive, and 67 (13%) had extensively positive margins. Increasingly involved
margins were associated with lobular type, tumor size, and adjacent DCIS in IBC
patients and lesion size in purely DCIS patients. In IBC patients, 17%, 49%, and
77% had re-excision after close, focally positive, and extensively positive
margins and residual disease incidence was 55%, 50%, and 70% respectively. In
purely DCIS patients, 26 (65%), 13 (87%), and 16 (94%) had re-excision after
close, focally positive, and extensively positive margins and residual disease
incidence was 39%, 46%, and 90% respectively. CONCLUSION: Incidence of residual
disease after focally positive margins was not different from close margins, but
was significantly higher after extensively positive margins. We recommend
quantifying extent of margin involvement in all pathology reports.
PMID- 28688725
TI - A Systematic Review of Interventions on Patients' Social and Economic Needs.
AB - CONTEXT: Healthcare systems are experimenting increasingly with interventions to
address patients' social and economic needs. This systematic review examines how
often and how rigorously interventions bridging social and medical care have been
evaluated. EVIDENCE ACQUISITION: The review included literature from PubMed
published between January 2000 and February 2017. Additional studies were
identified by reference searches and consulting local experts. Included studies
were based in the U.S.; addressed at least one social or economic determinant of
health (e.g., housing, employment, food insecurity); and were integrated within
the medical care delivery system. Data from included studies were abstracted in
June 2015 (studies published January 2000-December 2014) and in March 2017
(studies published January 2015-February 2017). EVIDENCE SYNTHESIS: Screening of
4,995 articles identified 67 studies of 37 programs addressing social needs.
Interventions targeted a broad range of social needs and populations. Forty
studies involved non-experimental designs. There was wide heterogeneity in
outcome measures selected. More studies reported findings associated with process
(69%) or social or economic determinants of health (48%) outcomes than health
(30%) or healthcare utilization or cost (27%) outcomes. Studies reporting health,
utilization, or cost outcomes reported mixed results. CONCLUSIONS: Healthcare
systems increasingly incorporate programs to address patients' social and
economic needs in the context of care. But evaluations of these programs to date
focus primarily on process and social outcomes and are often limited by poor
study quality. Higher-quality studies that include common health and healthcare
utilization outcomes would advance effectiveness research in this rapidly
expanding field.
PMID- 28688724
TI - PD-1 and PD-L1 expression in bone and soft tissue sarcomas.
AB - PD-1 and its ligands have been shown to play a significant role in evasion of
malignant tumour cells from the immune system. Last year, the Unites States Food
and Drug Administration (FDA) approved anti-PD-1 inhibitors for treatment of non
small cell lung carcinoma and recently expanded the use of immunotherapy for
metastatic urothelial cell carcinoma and Hodgkin lymphoma. However, studies on
expression of PD-1 and its ligand in malignant bone and soft tissue sarcoma are
sparse. In this study, we evaluated PD-1 and PD-L1 expression on variants of
liposarcomas and rhabdomyosarcomas, osteosarcomas and chondrosarcomas. Tissue
microarrays (TMAs) for liposarcomas (well differentiated, myxoid/round cell, and
pleomorphic), rhabdomyosarcomas (alveolar, embryonal, pleomorphic, and spindle
cell), conventional osteosarcomas and chondrosarcomas were stained for PD-1 and
PD-L1 antibodies. Adipose tissue, skeletal muscle, bone, osteochondroma and
lipoma were used as control and benign counterparts. Western blot was performed
to evaluate expression of PD-1 and PD-L1 in four sarcoma cell lines.
Osteosarcomas, chondrosarcomas, and all variants of liposarcomas and
rhabdomyosarcomas over-expressed PD-1 relative to normal tissue. Expression of PD
1 in rhabdomyosarcomas was associated with higher tumour stage. Only one case of
pleomorphic liposarcoma, one case of pleomorphic rhabdomyosarcoma and two cases
of alveolar rhabdomyosarcomas were positive for PD-L1. Normal adipose tissue,
skeletal muscle, and bone were negative for both PD-1 and PD-L1 and lipomas and
osteochondroma weakly expressed PD-1 but not PD-L1. Western blot confirmed the
presence of PD-1 protein in all four sarcoma cell lines. Overall, our results
showed cytoplasmic expression of PD-1 in the bone and soft tissue sarcomas, while
PD-L1 was negative. Whether these data are an indication for effectiveness of
immunotherapy in the management of malignant bone and soft tissue sarcomas
remains to be elucidated.
PMID- 28688726
TI - Associations Between County Wealth, Health and Social Services Spending, and
Health Outcomes.
AB - INTRODUCTION: Each year, the County Health Rankings rate the health outcomes of
each county in the U.S. A common refrain is that poor counties perform worse than
wealthier ones. This article examines that assumption and specifically analyzes
characteristics of counties that have performed better in terms of health
outcomes than their wealth alone would suggest. METHODS: Data from the 2013
County Health Rankings were used, as were 2012 financial and demographic
information collected by the U.S. Census Bureau. A logistic model was constructed
to examine the odds of a county "overperforming" in the rankings relative to
community wealth. Analyses were performed in 2016. RESULTS: Communities that were
wealthier performed better on the rankings. However, more than 800 of 3,141
counties overperformed by ranking in a better health outcomes quartile than their
county's wealth alone would suggest. Regression analyses found that for each
additional percentage point of total public spending that was allocated toward
community health care and public health, the odds of being an overperformer
increased by 3.7%. CONCLUSIONS: Community wealth correlates with health, but not
always. Population health outcomes in hundreds of counties overperform what would
be expected given community wealth alone. These counties tend to invest more in
community health care and public health spending and other social services.
Although the level of a community's wealth is outside the control of
practitioners, shifting the proportion of spending to certain social services may
positively impact population health.
PMID- 28688727
TI - Prevention of Type 2 Diabetes in U.S. Hispanic Youth: A Systematic Review of
Lifestyle Interventions.
AB - CONTEXT: Prevalence of type 2 diabetes mellitus (T2DM) in youth has increased
rapidly in recent decades along with rises in childhood obesity. Disparities in
risk and prevalence of T2DM are evident in Hispanic youth when compared with non
Hispanic whites. Targeted diabetes prevention programs have been recommended to
reduce risk prior to adulthood in this population. This systematic review
explores the effectiveness of lifestyle-based diabetes prevention interventions
for Hispanic youth. EVIDENCE ACQUISITION: PubMed, PsycINFO, Web of Science, and
CENTRAL were searched from database inception to March 1, 2017, for studies that
evaluated lifestyle-focused prevention trials targeting U.S. Hispanic youth under
age 18 years. Fifteen publications met criteria for inclusion. EVIDENCE
SYNTHESIS: Of the 15 studies, 11 were RCTs; four were uncontrolled. Interventions
were heterogeneous in intensity, content, and setting. Duration of most trials
was 12-16 weeks. Mean age of participants ranged from 9.8 to 15.8 years, sample
sizes were generally small, and the majority of participants were overweight (BMI
>=85th percentile). Three studies reported statistically significant reductions
in mean BMI, four in BMI z-score, and six in fasting glucose/insulin. Study
quality was moderate to high. Effect sizes were generally small to medium.
CONCLUSIONS: Evidence for the impact of lifestyle-based diabetes prevention
interventions targeting U.S. Hispanic youth remains limited. Few interventions
demonstrated success in reducing BMI and glucose regulation and follow-up times
were brief. More studies are needed that recruit larger samples sizes, extend
follow-up times, explore innovative delivery modalities, and examine
effectiveness across sex and age.
PMID- 28688728
TI - Community Policies and Programs to Prevent Obesity and Child Adiposity.
AB - INTRODUCTION: Evidence regarding impact of community policies and programs (CPPs)
to prevent child obesity is limited, and which combinations of strategies and
components are most important is not understood. The Healthy Communities Study
was an observational study to assess relationships of characteristics and
intensity of CPPs with adiposity, diet, and physical activity in children, taking
advantage of variation across the U.S. in community actions to prevent child
obesity. The study examined the association of CPPs to prevent child obesity with
measured BMI and waist circumference, hypothesizing that communities with more
comprehensive CPPs would have children with lower adiposity. METHODS: The study
included 130 communities selected by probability-based sampling or because of
known CPPs targeting child obesity. Data were collected at home visits on 5,138
children during 2013-2015. CPPs were scored for multiple attributes to create a
CPP intensity score. A CPP target behavior score reflected the number of distinct
target behaviors addressed. Scores were standardized with the smallest observed
score across communities being 0 and the largest 1. Multilevel regression
analysis in 2016 adjusted for community, household, and individual
characteristics. RESULTS: Higher CPP target behavior score was significantly
associated with lower BMI and waist circumference in a dose-response
relationship, with magnitude for the past 3 years of CPPs of 0.843 (p=0.013) for
BMI and 1.783 cm (p=0.020) for waist circumference. CONCLUSIONS: This study
provides plausible evidence that comprehensive CPPs targeting a greater number of
distinct physical activity and nutrition behaviors were associated with lower
child adiposity.
PMID- 28688731
TI - Informed decision making in the context of childhood immunization.
AB - OBJECTIVE: We aimed to assess informed decision making about childhood
immunization by measuring knowledge, deliberation and value-consistency.
Additionally, we investigated whether informed decision making is different for
parents who accept and parents who decline vaccination. METHODS: Parents of at
least one child between 3 months and 3,5 years of age were randomly selected from
a vaccination register and were asked to fill in an online questionnaire
measuring informed decision making. RESULTS: In total, 1615 parents completed the
questionnaire (16.2%). 77.6% of the parents were classified as having sufficient
knowledge, 34.3% of the decisions were deliberate, and 94% were value-consistent.
This resulted in 21% of parents who were classified as making an informed
decision. Vaccination decliners more often made a decision classified as informed
than vaccination acceptors (34.3% vs. 19.7%). When decliners made a decision
classified as uninformed, this was mainly due to insufficient knowledge, while
uninformed decisions among acceptors were mainly due to a low level of
deliberation. CONCLUSION AND PRACTICE IMPLICATIONS: Most parents made an
uninformed decision about childhood vaccinations. Decision aids and counseling by
child vaccine providers could improve the knowledge of decliners and motivate
acceptors to deliberate about their decision, and by that promote informed
decision making.
PMID- 28688732
TI - Self-attenuation corrections for Pb-210 in gamma-ray spectrometry using well and
coaxial HPGe detectors.
AB - Semi-empirical methods for 210Pb self-attenuation corrections were applied to
sediment samples in vial and cylindrical geometries, and were validated against
Monte Carlo modelling. Full Monte Carlo modelling (GESPECOR code) of the Cutshall
transmission method was successfully applied for the determination of mass
attenuation coefficients and efficiency transfer factors for coaxial detectors,
and compared with the values derived from the matrix chemical composition.
Simplified approaches were recommended when dealing with large numbers of
samples.
PMID- 28688730
TI - Use of Medical Orders for Scope of Treatment for Heart Failure Patients During
Postacute Care in Skilled Nursing Facilities.
AB - BACKGROUND: Individuals with heart failure (HF) who are hospitalized and admitted
to skilled nursing facilities (SNFs) are at high risk for rehospitalization and
death. The care preferences of this high-risk population have not been studied.
OBJECTIVES: To describe care preferences of patients with HF admitted to SNFs for
rehabilitation based on Medical Orders for Scope of Treatment (MOST)
documentation, and evaluate goal-concordant care based on MOST documentation,
emergency department (ED) visits, and hospitalization. DESIGN, SETTING, AND
PARTICIPANTS: Retrospective study of patients with HF in 35 SNFs enrolled in a
randomized controlled trial of HF-disease management versus usual care between
July 2014 and May 2016. MEASUREMENTS: Validity of MOST forms, care preference
documentation, and ED visits/hospitalizations within 60 days of SNF admission.
RESULTS: Of 370 patients (mean age 78.6 years, 58% women, 25% systolic HF), 278
(75%) had a MOST form in the SNF chart, of which 96 forms (35%) were invalid. The
most common reason for an invalid MOST form was missing date accompanying patient
or provider signature. Of 182 valid MOST forms, 47% of patients chose no
cardiopulmonary resuscitation ("No CPR"), 58% selected "Full Treatment," 17%
chose "Selective Treatment," and 23% chose "Comfort-Focused Treatment." Patients
who were older [odds ratio (OR) = 1.50, 95% confidence interval (CI) = 1.25,
1.81] and female (OR = 2.33, 95% CI = 1.18, 4.59) had higher odds of choosing "No
CPR." Sixty-six of 182 patients (36%) with valid MOST forms had an ED/hospital
visit within 60 days of SNF admission; only 3 patients received medical care that
was potentially discordant: all 3 chose "Comfort-Focused Treatment" and were
hospitalized for more than symptom management. CONCLUSION: Seventy-five percent
of patients with HF admitted to SNFs had care preferences documented using the
MOST form, and 95% received goal-concordant care based on care preferences
documented during the SNF admission. Clinicaltrials.gov # NCT01822912.
PMID- 28688733
TI - SPALAX NG: A breakthrough in radioxenon field measurement.
AB - Lessons-learned from 10 years of noble gas stations operation and dedicated R&D
allowed the design of a New Generation of station. In order to produce 60m3 air
equivalent Xenon samples every 8h, it implements: (i) larger sampler unit for
Xenon extraction (2 compressors and 8 nitrogen membranes), (ii) new noble gas
adsorbent (Ag@ZSM5), (iii) hardened components and (iv) new high resolution
coincidence low background spectrometer (HPGe/PIPSBox). Station expected
radioxenon sensitivity is lower than 0.3mBq/m3.
PMID- 28688729
TI - Cellular mechanosensing of the biophysical microenvironment: A review of
mathematical models of biophysical regulation of cell responses.
AB - Cells in vivo reside within complex microenvironments composed of both
biochemical and biophysical cues. The dynamic feedback between cells and their
microenvironments hinges upon biophysical cues that regulate critical cellular
behaviors. Understanding this regulation from sensing to reaction to feedback is
therefore critical, and a large effort is afoot to identify and mathematically
model the fundamental mechanobiological mechanisms underlying this regulation.
This review provides a critical perspective on recent progress in mathematical
models for the responses of cells to the biophysical cues in their
microenvironments, including dynamic strain, osmotic shock, fluid shear stress,
mechanical force, matrix rigidity, porosity, and matrix shape. The review
highlights key successes and failings of existing models, and discusses future
opportunities and challenges in the field.
PMID- 28688734
TI - First moves towards photoautotrophic synthetic cells: In vitro study of
photosynthetic reaction centre and cytochrome bc1 complex interactions.
AB - Following a bottom-up synthetic biology approach it is shown that vesicle-based
cell-like systems (shortly "synthetic cells") can be designed and assembled to
perform specific function (for biotechnological applications) and for studies in
the origin-of-life field. We recently focused on the construction of synthetic
cells capable to converting light into chemical energy. Here we first present our
approach, which has been realized so far by the reconstitution of photosynthetic
reaction centre in the membrane of giant lipid vesicles. Next, the details of our
ongoing research program are presented. It involves the use of the reaction
centre, the coenzyme Q-cytochrome c oxidoreductase, and the ATP synthase for
creating an autonomous synthetic cell. We show experimental results on the
chemistry of the first two proteins showing that they can efficiently sustain
light-driven chemical oscillations. Moreover, the cyclic pattern has been
reproduced in silico by a minimal kinetic model.
PMID- 28688735
TI - Implications of resin-based composite (RBC) restoration on cuspal deflection and
microleakage score in molar teeth: Placement protocol and restorative material.
AB - OBJECTIVE: To assess the cuspal deflection of standardised large mesio-occluso
distal (MOD) cavities in third molar teeth restored using conventional resin
based composite (RBC) or their bulk fill restorative counterparts compared with
the unbound condition using a twin channel deflection measuring gauge. Following
thermocycling, the cervical microleakage of the restored teeth was assessed to
determine marginal integrity. METHODS: Standardised MOD cavities were prepared in
forty-eight sound third molar teeth and randomly allocated to six groups.
Restorations were placed in conjunction with (and without) a universal bonding
system and resin restorative materials were irradiated with a light-emitting
diode light-curing-unit. The dependent variable was the restoration protocol,
eight oblique increments for conventional RBCs or two horizontal increments for
the bulk fill resin restoratives. The cumulative buccal and palatal cuspal
deflections from a twin channel deflection measuring gauge were summed, the
restored teeth thermally fatigued, immersed in 0.2% basic fuchsin dye for 24h,
sectioned and examined for cervical microleakage score. RESULTS: The one-way
analysis of variance (ANOVA) identified third molar teeth restored using
conventional RBC materials had significantly higher mean total cuspal deflection
values compared with bulk fill resin restorative restoration (all p<0.0001). For
the conventional RBCs, Admira Fusion (bonded) third molar teeth had significantly
the lowest microleakage scores (all p<0.001) while the Admira Fusion x-tra
(bonded) bulk fill resin restored teeth had significantly the lowest microleakage
scores compared with Tetric EvoCeram Bulk Fill (bonded and non-bonded) teeth (all
p<0.001). SIGNIFICANCE: Not all conventional RBCs or bulk fill resin restoratives
behave in a similar manner when used to restore standardised MOD cavities in
third molar teeth. It would appear that light irradiation of individual
conventional RBCs or bulk fill resin restoratives may be problematic such that
material selection is vital in the absence of clinical data.
PMID- 28688736
TI - Growth studies on microalgae Euglena sanguinea in various natural eco-friendly
composite media to optimize the lipid productivity.
AB - The environmental and culture conditions of a potential microalgae Euglena
sanguinea were optimized for maximizing the biomass productivity. It was found
that the organic macronutrient from poultry litter and organic micronutrient of
seaweed extract are very effective to enhance the lipid production.
Complementing, these organic nutrients with commercial NPK fertilizer, boost up
the lipid productivity by 30.9% in comparison with the established standard
Euglena medium. The fatty acid profile of the extracted oil by GC-MS reveals its
conformity with commercial diesel.
PMID- 28688737
TI - Development of biocathode during repeated cycles of bioelectrochemical conversion
of carbon dioxide to methane.
AB - Functioning biocathodes are essential for electromethanogenesis. This study
investigated the development of a biocathode from non-acclimated anaerobic sludge
in an electromethanogenesis cell at a cathode potential of -0.7V (vs. standard
hydrogen electrode) over four cycles of repeated batch operations. The CO2-to-CH4
conversion rate increased (to 97.7%) while the length of the lag phase decreased
as the number of cycles increased, suggesting that a functioning biocathode
developed during the repeated subculturing cycles. CO2-resupply test results
suggested that the biocathode catalyzed the formation of CH4 via both direct and
indirect (H2-mediated) electron transfer mechanisms. The biocathode archaeal
community was dominated by the genus Methanobacterium, and most archaeal
sequences (>89%) were affiliated with Methanobacterium palustre. The bacterial
community was dominated by putative electroactive bacteria, with Arcobacter,
which is rarely observed in biocathodes, forming the largest population. These
electroactive bacteria were likely involved in electron transfer between the
cathode and the methanogens.
PMID- 28688738
TI - Challenges and recent advances in biochar as low-cost biosorbent: From batch
assays to continuous-flow systems.
AB - Over the past few years, the increasing amount of pollutants and their diversity
demand to develop versatile low-cost adsorption systems. The use of biomass
feedstock such as agricultural residues, wood chips, manure or municipal solid
wastes as source to produce low-cost biosorbent, and the new advances in their
synthesis have encouraged remarkable efforts towards the development of biochar
"on demand" in which their characteristics can be improved. This new trend opens
the potential of biochar application in the removal of pollutants from
wastewater, however, its use in environmental management requires the development
of full-scale biosorption in engineered systems. Thus, this paper provides a
brief review of recent progress in the research and practical application of
biochar with a special emphasis on its potential to reduce the pollutants present
in wastewater or to render them harmless. Furthermore, research gaps and
uncertainties detected in their scale-up in continuous-flow systems are
highlighted.
PMID- 28688739
TI - Microbial conversion of biomass into bio-based polymers.
AB - The worldwide market for plastics is rapidly growing, and plastics polymers are
typically produced from petroleum-based chemicals. The overdependence on
petroleum-based chemicals for polymer production raises economic and
environmental sustainability concerns. Recent progress in metabolic engineering
has expanded fermentation products from existing aliphatic acids or alcohols to
include aromatic compounds. This diversity provides an opportunity to expand the
development and industrial uses of high-performance bio-based polymers. However,
most of the biomonomers are produced from edible sugars or starches that compete
directly with food and feed uses. The present review focuses on recent progress
in the microbial conversion of biomass into bio-based polymers, in which
fermentative products from renewable feedstocks serve as biomonomers for the
synthesis of bio-based polymers. In particular, the production of biomonomers
from inedible lignocellulosic feedstocks by metabolically engineered
microorganisms and the synthesis of bio-based engineered plastics from the
biological resources are discussed.
PMID- 28688740
TI - Reading deficits in schizophrenia and their relationship to developmental
dyslexia: A review.
AB - Although schizophrenia and developmental dyslexia are considered distinct
disorders in terms of clinical presentation and functional outcome, they both
involve disruption in the processes that support skilled reading, including
language, auditory perception, visual perception, oculomotor control, and
executive function. Further, recent work has proposed a common neurodevelopmental
basis for the two disorders, as suggested by genetic and pathophysiological
overlap. Thus, these lines of research suggest that reading may be similarly
impacted in schizophrenia and dyslexia. In this review, we survey research on
reading abilities in individuals with schizophrenia, and review the potential
mechanisms underlying reading deficits in schizophrenia that may be shared with
those implicated in dyslexia. Elucidating the relationship between reading
impairment in schizophrenia and dyslexia could allow for a better understanding
of the pathophysiological underpinnings of schizophrenia, and could facilitate
remediation of cognitive deficits that impact day-to-day functioning.
PMID- 28688742
TI - Effects of adjunctive fluvoxamine on metabolic parameters and psychopathology in
clozapine-treated patients with schizophrenia: A 12-week, randomized, double
blind, placebo-controlled study.
AB - OBJECTIVE: Numerous studies have demonstrated that fluvoxamine has considerable
pharmacokinetic and pharmacodynamic interactions with clozapine. We conducted a
12-week, randomized, double-blind, placebo-controlled study to evaluate the
effects of fluvoxamine on metabolic parameters and psychopathology in clozapine
treated patients with schizophrenia. METHODS: We recruited 85 patients who
received a DSM-IV diagnosis of schizophrenia. Eligible patients were randomized
to receive fluvoxamine 50mg/day plus clozapine 100mg/day or clozapine 300mg/day.
We studied metabolic parameters, psychopathology, and drug levels at baseline and
4, 8, and 12weeks after the intervention. Plasma levels of clozapine,
norclozapine, clozapine N-oxide, and fluvoxamine were determined using high
performance liquid chromatography with ultraviolet detection. RESULTS: No
significant difference was observed in baseline characteristics between the two
groups. Clozapine-fluvoxamine combined treatment significantly attenuated the
increments in body weight, insulin resistance, and levels of insulin, glucose,
and triglycerides compared with clozapine monotherapy. Both groups exhibited
significant improvements in their Positive and Negative Syndrome Scale (PANSS)
total and negative scores. The combined treatment group showed significant
reduction in the PANSS general psychopathology scores compared with the
monotherapy group. No difference was observed in the plasma clozapine level
between the two groups. The monotherapy group showed higher levels of
norclozapine and clozapine N-oxide than the combined group. CONCLUSIONS: Compared
with clozapine monotherapy, treatment with adjunctive fluvoxamine with clozapine
for 12weeks can alleviate body weight gain and metabolic abnormalities in
patients with schizophrenia, without sacrificing the clinical effect. Clinicians
should interpret these findings cautiously considering the short duration of this
study. The study was registered at www.clinicaltrials.gov (NCT01401491).
PMID- 28688741
TI - Stronger default mode network connectivity is associated with poorer clinical
insight in youth at ultra high-risk for psychotic disorders.
AB - Impaired clinical insight (CI) is a common symptom of psychotic disorders and a
promising treatment target. However, to date, our understanding of how
variability in CI is tied to underlying brain dysfunction in the clinical high
risk period is limited. Developing a stronger conception of this link will be a
vital first step for efforts to determine if CI can serve as a useful prognostic
indicator. The current study investigated whether variability in CI is related to
major brain networks in adolescents and young adults at ultra high-risk (UHR) of
developing psychosis. Thirty-five UHR youth were administered structured clinical
interviews as well as an assessment for CI and underwent resting-state magnetic
resonance imaging scans. Functional connectivity was calculated in the default
mode network (DMN) and fronto-parietal network (FPN), two major networks that are
dysfunctional in psychosis and are hypothesized to affect insight. Greater DMN
connectivity between the posterior cingulate/precuneus and ventromedial
prefrontal cortex (DMN) was related to poorer CI (R2=0.399). There were no
significant relationships between insight and the FPN. This is the first study to
relate a major brain network to clinical insight before the onset of psychosis.
Findings are consistent with evidence if a hyperconnected DMN in schizophrenia
and UHR, and similar to a previous study of insight and connectivity in
schizophrenia. Results suggest that a strongly connected DMN may be related to
poor self-awareness of subthreshold psychotic symptoms in UHR adolescents and
young adults.
PMID- 28688743
TI - [Detection of RAS genes mutation using the Cobas(r) method in a private
laboratory of pathology: Medical and economical study in comparison to a public
platform of molecular biology of cancer].
AB - In France, determination of the mutation status of RAS genes for predictive
response to anti-EGFR targeted treatments is carried out by public platforms of
molecular biology of cancer created by the French National Cancer Institute. This
study aims to demonstrate the feasibility of these analyses by a private
pathology laboratory (MEDIPATH) as per the requirements of accreditation. We
retrospectively studied the mutation status of KRAS and NRAS genes in 163 cases
of colorectal metastatic cancer using the Cobas(r) technique. We compared our
results to those prospectively obtained through pyrosequencing and allelic
discrimination by the genetic laboratory of solid tumors at the Nice University
Hospital (PACA-EST regional platform). The results of both series were identical:
98.7% positive correlation; negative correlation of 93.1%; overall correlation of
95.7% (Kappa=0.92). This study demonstrates the feasibility of molecular analysis
in a private pathology laboratory. As this practice requires a high level of
guarantee, its accreditation, according to the NF-EN-ISO15189 quality compliance
French standard, is essential. Conducting molecular analysis in this context
avoids the steps of routing the sample and the result between the pathology
laboratory and the platform, which reduces the overall time of rendering the
result. In conclusion, the transfer of some analysis from these platforms to
private pathology laboratories would allow the platforms to be discharged from a
part of routine testing and therefore concentrate their efforts to the
development of new analyses constantly required to access personalized medicine.
PMID- 28688744
TI - [Screening of hepatocellular carcinoma in patients with uncomplicated cirrhosis
in real life: Practices survey of general practionners from three towns of Seine
Saint-Denis (north-east suburb of Paris)].
AB - Cirrhosis is a frequent and severe pathology life threatening, due to the
occurrence of complications including hepatocellular carcinoma. In order to
assess the degree of conformity, of practices, with the French guidelines for the
surveillance of patients with compensated cirrhosis and the primary prevention of
complications, published in 2007, all general practitioners practicing in three
towns from north-east suburb of Paris (Seine-Saint-Denis) representing a
population pool of 186 286 inhabitants were asked during the first quarter of
2012 for the face-to-face administration of a standardized questionnaire. Based
on the 20 questions, individual practices were analyzed and a compliance score
limited to hepatocellular carcinoma screening was established. Of the 106
practitioners surveyed, 40 have agreed to participate (85% of men, mostly based
in Aulnay-sous-Bois or Sevran with an average exercice of 22years). The declared
practices were heterogeneous and did insuffisantly comply with the
recommendations (mean score 1.9/3). The intent of surveillance was not influenced
by the origin or severity of cirrhosis. Screening for HCC was based on
appropriate tests (abdominal ultrasound, alpha-foetoprotein serum) but with
optimal half-yearly intervals in less than half of the cases. Improved
communication to general private practitioners of HAS recommendations for
patients with compensated cirrhosis could optimize the prescribing of screening
tests for hepatocellular carcinoma.
PMID- 28688745
TI - [2017 ASCO: Complete androgen blockade strikes back].
PMID- 28688746
TI - [Patient participation in medical decision-making: From concept to reality in
oncology].
PMID- 28688747
TI - [Clinical research activity of the French cancer cooperative network: Overview
and perspectives].
AB - INTRODUCTION: The French Cancer Plan 2014-2019 stresses the importance of
strengthening collaboration between all stakeholders involved in the fight
against cancer, including cancer cooperative groups and intergroups. This survey
aimed to describe the basics characteristics and clinical research activity among
the Cancer Cooperative Groups (Groupes cooperateurs en oncologie). The second
objective was to identify facilitators and barriers to their research activity.
METHODS: A questionnaire was sent to all the clinicians involved in 2014 as
investigators in a clinical trial sponsored by one of the ten members of the
Cancer Cooperative Groups network. The questions were related to their profile,
research activity and the infrastructure existing within their healthcare center
to support clinical research and related compliance activities. RESULTS: In
total, 366 investigators responded to our survey. The academic clinical trials
sponsored by the Cancer Cooperative Groups represented an important part of the
research activity of the investigators in France in 2014. These academic groups
contributed to the opening of many research sites throughout all regions in
France. Factors associated with a higher participation of investigators (more
than 10 patients enrolled in a trial over a year) include the existing support of
healthcare professionals (more than 2 clinical research associate (CRA) OR=11.16
[3.82-32.6] compared to none) and the practice of their research activity in a
University Hospital Center (CHU) rather than a Hospital Center (CH) (OR=2.15
[1.20-3.83]). CONCLUSION: This study highlighted factors that can strengthen
investigator clinical research activities and subsequently improve patient access
to evidence-based new cancer therapies in France.
PMID- 28688748
TI - Congenital muscular dystrophies in the UK population: Clinical and molecular
spectrum of a large cohort diagnosed over a 12-year period.
AB - Congenital muscular dystrophies (CMDs) are clinically and genetically
heterogeneous conditions; some fatal in the first few years of life and with
central nervous system involvement, whereas others present a milder course. We
provide a comprehensive report of the relative frequency and clinical and genetic
spectrum of CMD in the UK. Genetic analysis of CMD genes in the UK is centralised
in London and Newcastle. Between 2001 and 2013, a genetically confirmed diagnosis
of CMD was obtained for 249 unrelated individuals referred to these services. The
most common CMD subtype was laminin-alpha2 related CMD (also known as MDC1A,
37.4%), followed by dystroglycanopathies (26.5%), Ullrich-CMD (15.7%), SEPN1
(11.65%) and LMNA (8.8%) gene related CMDs. The most common dystroglycanopathy
phenotype was muscle-eye-brain-like disease. Fifteen patients carried mutations
in the recently discovered ISPD, GMPPB and B3GALNT2 genes. Pathogenic allelic
mutations in one of the CMD genes were also found in 169 unrelated patients with
milder phenotypes, such as limb girdle muscular dystrophy and Bethlem myopathy.
In all, we identified 362 mutations, 160 of which were novel. Our results provide
one of the most comprehensive reports on genetics and clinical features of CMD
subtypes and should help diagnosis and counselling of families with this group of
conditions.
PMID- 28688749
TI - Cross-level interaction between individual socioeconomic status and regional
deprivation on overall survival after onset of ischemic stroke: National health
insurance cohort sample data from 2002 to 2013.
AB - INTRODUCTION: The literature on stroke mortality and neighborhood effect is
characterized by studies that are often Western society-oriented, with a lack of
racial and cultural diversity. We estimated the effect of cross-level interaction
between individual and regional socioeconomic status on the survival after onset
of ischemic stroke. METHODS: We selected newly diagnosed ischemic stroke patients
from 2002 to 2013 using stratified representative sampling data of 1,025,340
subjects. A total of 37,044 patients over the 10 years from 2004 to 2013 had
newly diagnosed stroke. We calculated hazard ratios (HR) of 12- and 36-month
mortality using the Cox proportional hazard model, with the reference group as
stroke patients with high income in advantaged regions. RESULTS: For the middle
income level, the patients in advantaged regions showed low HRs for overall
mortality (12-month HR 1.27; 95% confidence interval [CI], 1.13-1.44; 36-month HR
1.25; 95% CI, 1.14-1.37) compared to the others in disadvantaged regions (12
month HR 1.36; 95% CI, 1.19-1.56; 36-month HR 1.30; 95% CI, 1.17-1.44).
Interestingly, for the low income level, the patients in advantaged regions
showed high HRs for overall mortality (12-month HR 1.27; 95% CI, 1.13-1.44; 36
month HR 1.33; 95% CI, 1.22-1.46) compared to the others in disadvantaged regions
(12-month HR 1.25; 95% CI, 1.09-1.43; 36-month HR 1.30; 95% CI, 1.18-1.44).
CONCLUSION: Although we need to perform further investigations to determine the
exact mechanisms, regional deprivation, as well as medical factors, might be
associated with survival after onset of ischemic stroke in low-income patients.
PMID- 28688750
TI - It takes a village: Fixed-effects analysis of neighborhood collective efficacy
and children's development.
AB - BACKGROUND: Previous studies suggest that neighborhood social capital is
associated with children's mental health. The purpose of this study was to
examine the association between neighborhood collective efficacy and children's
psychosocial development. METHODS: We used data on children and their parents (n
= 918) who were part of the Japanese study of Stratification, Health, Income, and
Neighborhood (JSHINE) from 2010 to 2013 (wave 1 and wave 2). Households were
recruited from the Tokyo metropolitan area through clustered random sampling.
Changes in children's psychosocial development (assessed using a child behavioral
checklist) between waves 1 and 2 were regressed on parents' perceptions of
changes in neighborhood collective efficacy (social cohesion and informal social
control). RESULTS: Change in perception of neighborhood social cohesion was
inversely associated with change in child total problems (beta = -0.22; 95%
confidence interval [CI]: -0.37 to -0.001; effect size d = -0.03). Change in
perceptions of neighborhood informal social control was inversely associated with
change in children's externalizing problems (beta = -0.16; 95% CI: -0.30 to
0.03; d = -0.02). CONCLUSIONS: The results of these fixed-effects models suggest
that strengthening neighborhood collective efficacy is related to improvements in
child psychosocial development.
PMID- 28688752
TI - Comparison of effects of LLLT and LIPUS on fracture healing in animal models and
patients: A systematic review.
AB - The aim of this paper is to study the in vivo potency of low-level laser therapy
(LLLT) and low intensity pulsed ultrasound (LIPUS) alone, accompanied by bone
grafts, or accompanied by other factors on fracture healing in animal models and
patients. In this paper, we aim to systematically review the published scientific
literature regarding the use of LLLT and LIPUS to accelerate fracture healing in
animal models and patients. We searched the PubMed database for the terms LLLT or
LIPUS and/or bone, and fracture. Our analysis also suggests that both LIPUS and
LLLT may be beneficial to fracture healing in patients, and that LIPUS is more
effective. These finding are of considerable importance in those treatments with
a LIPUS, as a laser device may reduce healing time. The most clinically relevant
impact of the LIPUS treatment could be a significant reduction in the proportion
of patients who go on to develop a nonunion. If it is confirmed that the
therapeutic influence is true and reliable, patients will obtain benefits from
LIPUS and LLLT. Further clinical trials of high methodological quality are needed
in order to determine the optimal role of LIPUS and LLLT in fracture healing in
patients.
PMID- 28688751
TI - Electro-mechanical conditioning of human iPSC-derived cardiomyocytes for
translational research.
AB - RATIONALE: Impaired maturation of human iPSC-derived cardiomyocytes (hiPSC-CMs)
currently limits their use in experimental research and further optimization is
required to unlock their full potential. OBJECTIVE: To push hiPSC-CMs towards
maturation, we recapitulated the intrinsic cardiac properties by electro
mechanical stimulation and explored how these mimetic biophysical cues interplay
and influence the cell behaviour. METHODS AND RESULTS: We introduced a novel
device capable of applying synchronized electrical and mechanical stimuli to
hiPSC-CM monolayers cultured on a PDMS membrane and evaluated effects of
conditioning on cardiomyocyte structure and function. Human iPSC-CMs retained
their cardiac phenotype and displayed adaptive structural responses to electrical
(E), mechanical (M) and combined electro-mechanical (EM) stimuli, including
enhanced membrane N-cadherin signal, stress-fiber formation and sarcomeric length
shortening, most prominent under the EM stimulation. On the functional level, EM
conditioning significantly reduced the transmembrane calcium current, resulting
in a shift towards triangulation of intracellular calcium transients. In
contrast, E and M stimulation applied independently increased the proportion of
cells with L-Type calcium currents. In addition, calcium transients measured in
the M-conditioned samples advanced to a more rectangular shape. CONCLUSION: The
new methodology is a simple and elegant technique to systematically investigate
and manipulate cardiomyocyte remodelling for translational applications. In the
present study, we adjusted critical parameters to optimize a regimen for hiPSC-CM
transformation. In the future, this technology will open up new avenues for
electro-mechanical stimulation by allowing temporal and spatial control of
stimuli which can be easily scaled up in complexity for cardiac development and
disease modelling.
PMID- 28688754
TI - Strategy for erythroid differentiation in ex vivo cultures: Lentiviral genetic
modification of human hematopoietic stem cells with erythropoietin gene.
AB - If cultured in appropriate conditions, such as supplementing culture media with
costly cytokines and growth factors, hematopoietic stem/progenitor cells (HSPCs)
from different origins have shown to be an adequate source of erythroid cells.
This requirement turns erythroid cells production into a complicated process to
be scaled-up for future applications. The aim of our work was to genetically
modify HSPCs with human erythropoietin (hEPO) sequence by lentiviral transgenesis
in order for cells to secrete the hormone into the culture medium. Initially, we
evaluated erythroid differentiation in colony forming units (CFU) assays and
further analyzed cell expansion and erythroid differentiation throughout time in
suspension cultures by flow cytometry and May-Grunwald-Giemsa staining.
Additionally, we studied hEPO production and its isoforms profile. The different
assessment approaches demonstrated erythroid differentiation, which was
attributed to the hEPO secreted by the HSPCs. Our data demonstrate that it is
possible to develop culture systems in which recombinant HSPCs are self-suppliers
of hEPO. This feature makes our strategy attractive to be applied in
biotechnological production processes of erythroid cells that are currently under
development.
PMID- 28688753
TI - Antiviral effects of Retro-2cycl and Retro-2.1 against Enterovirus 71 in vitro
and in vivo.
AB - Enterovirus 71 (EV71) is one of the causative pathogens of hand, foot and mouth
disease (HFMD), especially the form associated with fatal neurological disorders.
Sustained outbreaks of EV71 infections remain a serious health threat worldwide.
However, no antiviral agent against EV71 for clinical therapy has been approved.
Retro-2cycl and Retro-2.1 are inhibitors of several pathogens specifically
targeting the intracellular vesicle transport, which also participates in the
EV71 lifecycle processes including progeny virus release. Here, we reported that
Retro-2cycl and Retro-2.1, respectively, could inhibit EV71 infection with 50%
effective concentrations of 12.56 MUM and 0.05 MUM in a cytopathic effect
inhibition assay and showed relatively low cytotoxicity with 50% cytotoxicity
concentrations of more than 500 MUM and 267.80 MUM. Preliminary mechanism studies
revealed that Retro-2cycl and Retro-2.1 did not inhibit EV71 protein synthesis or
RNA replication but could block progeny EV71 release specifically. Furthermore,
administration of Retro-2cycl at the dose of 10 mg/kg significantly protected 90%
of newborn mice from lethal EV71 challenge. Consequently, our results for the
first time identified Retro-2cycl and Retro-2.1 as effective inhibitors of EV71
as well as lead compounds, which would contribute to anti-EV71 drug development.
We also identified progeny virus release and the intracellular vesicle transport
as antiviral targets for EV71.
PMID- 28688755
TI - Simultaneous masking between electric and acoustic stimulation in cochlear
implant users with residual low-frequency hearing.
AB - Ipsilateral electric-acoustic stimulation (EAS) is becoming increasingly
important in cochlear implant (CI) treatment. Improvements in electrode designs
and surgical techniques have contributed to improved hearing preservation during
implantation. Consequently, CI implantation criteria have been expanded toward
people with significant residual low-frequency hearing, who may benefit from the
combined use of both the electric and acoustic stimulation in the same ear.
However, only few studies have investigated the mutual interaction between
electric and acoustic stimulation modalities. This work characterizes the
interaction between both stimulation modalities using psychophysical masking
experiments and cone beam computer tomography (CBCT). Two psychophysical
experiments for electric and acoustic masking were performed to measure the
hearing threshold elevation of a probe stimulus in the presence of a masker
stimulus. For electric masking, the probe stimulus was an acoustic tone while the
masker stimulus was an electric pulse train. For acoustic masking, the probe
stimulus was an electric pulse train and the masker stimulus was an acoustic
tone. Five EAS users, implanted with a CI and ipsilateral residual low-frequency
hearing, participated in the study. Masking was determined at different
electrodes and different acoustic frequencies. CBCT scans were used to determine
the individual place-pitch frequencies of the intracochlear electrode contacts by
using the Stakhovskaya place-to-frequency transformation. This allows the
characterization of masking as a function of the difference between electric and
acoustic stimulation sites, which we term the electric-acoustic frequency
difference (EAFD). The results demonstrate a significant elevation of detection
thresholds for both experiments. In electric masking, acoustic-tone thresholds
increased exponentially with decreasing EAFD. In contrast, for the acoustic
masking experiment, threshold elevations were present regardless of the tested
EAFDs. Based on the present findings, we conclude that there is an asymmetry
between the electric and the acoustic masker modalities. These observations have
implications for the design and fitting of EAS sound-coding strategies.
PMID- 28688756
TI - Mechanical behavior of rf-treated thrombus in mechanical thrombectomy.
AB - Intra-arterial mechanical thrombectomy (IAMT) treatments for ischemic stroke have
higher recanalization rate, longer treatment time window and lower risk of
symptomatic intracerebral hemorrhage (sICH). However, distal embolization may
occur because of loose fragments produced during maceration and engagement. The
naturally coagulated thrombus is fragile and has poor binding with thrombectomy
device. Improvement of thrombus-device binding can reduce fragments breaking
loose during wire pull and enhance protein crosslinking in the thrombus that can
increase fragmentation resistance. The effects of in-situ applied radio frequency
(rf) treatment on thrombus-wire binding and interfacial fracture have been
examined in this study using wire pull tests that are mechanically analogous to
the embolus retrieval method in thrombectomy. Wire inserted into a thrombus was
pull tested after rf-treatment. Pull test results showed that rf-treatment
improves binding and reduces thrombus slippage from over 90% to less than 10%.
Fracture pull test results also showed that fracture energy density of thrombus
device interface increased 40X after rf-treatment. The dramatic increase in
resistance against fracture suggests that the use of in-situ rf-treatment is a
promising treatment addition to reduce distal embolization and improve clinical
outcomes in mechanical thrombectomy.
PMID- 28688757
TI - [Description and role of bacteriological techniques in the management of lung
infections].
AB - Acute pneumonias occur in a variety of clinical settings and accurate
identification of bacterial causes is extremely important. No microbiological
tool is either 100 % sensitive or 100 % specific, and despite investigations,
aetiology remains unanswered in more than 30 % of pneumonia. No sample may be
necessary for patients treated as outpatients, non invasive respiratory specimens
are preferred in hospitalised individuals (community or healthcare associated),
while invasive specimens are used as second line for community acquired pneumonia
(CAP) in intensive care, and in the first line where pneumonia occurs in
immunosuppressed patients. Bacterial cultures have an important place, if the
sample is taken before the introduction of antibiotic therapy. Some contexts may
justify the use of blood cultures, testing for urinary antigens or serology. PCR
is already becoming available as a daily service but the short-term future
probably belongs to molecular multiplex panels capable of detecting many
microorganisms within hours, especially in severe CAP resuscitation and in
pneumonia in the immunosuppressed. High-throughput sequencing nucleotide
techniques will soon revolutionize microbiological diagnosis in respiratory
medicine, as in other areas of infectious diseases.
PMID- 28688758
TI - [European birth cohorts: Early life exposure to microorganisms and health
impact].
AB - In recent years, many birth cohorts have been initiated in Europe, to assess the
early life microbiological exposure of children in the indoor environment and
better understanding the different effects (adverse/protectors) on health. The
results of 12 European cohorts, with different methodologies for exposure and
allergic risk assessment are summarized in this review. Four meta-analyzes of
cohort are presented too. Microbiological researches in indoor environment seem
to turn to a metrology of microbiological exposure, but few studies provide real
quantitative data. Thus, the establishment of dose-effect relationship is not
possible and can only be done by having a global view of the situation, provided
by an identical metrological approach in the different studies, in a large-scale,
in the context of large birth cohorts with children followed with strict criteria
to establish the clinical diagnosis.
PMID- 28688759
TI - [Respiratory infections caused by slow-growing bacteria: Nocardia, Actinomyces,
Rhodococcus].
AB - INTRODUCTION: Pneumonia caused by slow-growing bacteria is rare but sometimes
severe. STATE OF THE ART: These infections share many similarities such as
several differential diagnoses, difficulties to identify the pathogen, the
importance of involving the microbiologist in the diagnostic investigation and
the need for prolonged antibiotic treatment. However, major differences
distinguish them: Nocardia and Rhodococcus infect mainly immunocompromised
patients while actinomycosis also concerns immunocompetent patients; the severity
of nocardioses is related to their hematogenous spread while locoregional
extension by contiguity makes the gravity of actinomycosis. PROSPECTIVE: For
these diseases, molecular diagnostic tools are essential, either to obtain a
species identification and guide treatment in the case of nocardiosis or to
confirm the diagnosis from a biological sample. Treatment of these infections is
complex due to: (1) the limited data in the literature; (2) the need for
prolonged treatment of several months; (3) the management of toxicities and drug
interactions for the treatment of Nocardia and Rhodococcus. CONCLUSION: Close
cooperation between pneumonologists, infectious disease specialists and
microbiologists is essential for the management of these patients.
PMID- 28688760
TI - [Once weekly L-thyroxine treatment in non-compliance: A case report].
AB - INTRODUCTION: The non-adherence to substitutive treatment by L-thyroxine is the
main cause of the discordance between high thyrotropin values and high doses of
the drug. OBSERVATION: In a 36-year-old patient with post-surgery hypothyroidism,
thyrotropin values ranged between 100 and 400 mUI/L, although daily replacement
therapy included 300 MUg of L-thyroxine and 75 MUg of L-triiodothyronine. The
oral loading test with L-thyroxine was normal and thyrotropin serum level
returned to normal values under weekly oral administration of 1000 MUg L
thyroxine. CONCLUSION: The strategy of non-adherence treatment in hypothyroidism
is well defined with oral testing of L-thyroxine, followed by oral or parenteral
weekly administration of the drug. The L-thyroxine oral test is the gold standard
for diagnosis after eliminating of the other conventional causes: drug
interactions or digestive malabsorption. L-thyroxine treatment should be
discussed on a case-by-case basis, either daily under surveillance or once weekly
oral or parenteral high dose.
PMID- 28688761
TI - Long non-coding RNA Gm4419 promotes trauma-induced astrocyte apoptosis by
targeting tumor necrosis factor alpha.
AB - Traumatic brain injury (TBI) remains a life-threatening disease. Accumulating
evidences have showed that neuroinflammatory response is a critical biological
event in the progression of TBI induced astrocyte damage. However, the exact
mechanisms are not well understood. In this study, we demonstrated that long non
coding RNA (lncRNA) Gm4419 promoted trauma-induced astrocyte apoptosis by up
regulating the expression of inflammatory cytokine tumor necrosis factor alpha
(TNF-alpha). We observed that Gm4419 was aberrantly induced after injury on
astroglial cells in vitro. Overexpression of Gm4419 in injury-treated astrocytes
increased protein expressions of TNF-alpha, Bax, cleaved caspase-3 and cleaved
caspase-9, decreased levels of Bcl-2 and CyclinD1, and significantly led to
cellular apoptosis. Mechanically, Gm4419 transcript could function as a sponge
for miR-466l and miR-466l could target TNF-alpha 3' UTR for degradation and
translation inhibition. Therefore, Gm4419 could up-regulate TNF-alpha expression
by competitively binding miR-466l and then contribute to inflammatory damage as
well as astrocyte apoptosis during TBI. Generally speaking, our findings provide
better understandings of the mechanism underlying Gm4419 in trauma-induced
neuroinflammation and neurological deficits. Thus, the present study would expand
the insight into the novel approaches for TBI therapy.
PMID- 28688762
TI - Thioredoxin attenuates oxidized low-density lipoprotein induced oxidative stress
in human umbilical vein endothelial cells by reducing NADPH oxidase activity.
AB - Oxidative stress is recognized as one of the most important contributing factors
to the development of atherosclerosis. Oxidized low-density lipoprotein (ox-LDL)
can induce vascular reactive oxygen species (ROS) production, trigger endothelial
dysfunction and initiate the progression of atherosclerosis. Previous studies
have demonstrated that thioredoxin-1 (Trx) is one of the key regulators of
intracellular redox, which is pivotal in atherogenesis. However, the regulation
mechanism is still unclear. In this study, we investigated the effects of Trx1 on
NADPH oxidase in human umbilical vein endothelial cells (HUVECs), whose ROS level
is mainly produced by NADPH oxidase, especially Nox4 isoform. Our data
demonstrated that Trx decreased NADPH oxidase activity, ROS production and ICAM-1
expression in ox-LDL treated HUVECs. Genetic gain-of-function and loss-of
function studies showed that Trx1 suppressed ox-LDL-induced Nox4 and p22phox
expression. A co-immunoprecipitation assay indicated that Trx1 decreased Nox4
p22phox complex level during ox-LDL stimulation. Transient transfection of Nox4
and p22phox significantly increased intracellular ROS generation, which could be
blocked by Trx overexpression. In addition, Trx overexpression also prevented ox
LDL-induced Nox2 and Rac1 protein levels. These results suggest that Trx
suppresses NADPH oxidase activity in vascular endothelia under pathological
conditions and may prevent the initiation of atherosclerosis by attenuating
exceeding ROS production.
PMID- 28688763
TI - Protective function of SLC30A10 induced via PERK-ATF4 pathway against 1-methyl-4
phenylpyridinium.
AB - Solute carrier family 30 member 10 (SLC30A10) has been known as manganese
transporter. It has been suggested that neurodegenerative diseases are related
with cellular stress such as oxidative stress or endoplasmic reticulum (ER)
stress. However, it remains unknown whether SLC30A10 is actually involved in
several intracellular stress. We found that the level of Slc30a10 was increased
in midbrain of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice.
Therefore, we further investigated the role of SLC30A10 in the 1-methyl-4
phenylpiridium ion (MPP+)-induced intracellular stress, and the molecular
mechanism underlying SLC30A10 induction by MPP+ treatment. In human neuroblastoma
cell line (SH-SY5Y) treated with MPP+ (1 mM), the SLC30A10 mRNA level was
significantly increased, and in addition, the expression of CHOP, which is known
as one of ER stress markers, was significantly increased by MPP+. Interestingly,
the level of SLC30A10 mRNA was significantly increased by tunicamycin as an ER
stressor, suggesting that the induction of SLC30A10 by MPP+ was caused via ER
stress. Considering that PKR-like endoplasmic reticulum kinase (PERK) pathway is
activated under ER stress induced by MPP+, we investigated whether the expression
of SLC30A10 is increased through ATF4, which is major transcription factor in
PERK pathway. The increase of SLC30A10 expression in MPP+-treated cells was
eliminated by ATF4 knockdown. And the protective role of SLC30A10 against MPP+
induced ER stress was confirmed by measuring cell viability in SLC30A10 knockdown
cells. In conclusion, SLC30A10 is thought to have protective role for MPP+
induced toxicity via PERK-ATF4 pathway.
PMID- 28688764
TI - RELT family members activate p38 and induce apoptosis by a mechanism distinct
from TNFR1.
AB - Receptor Expressed in Lymphoid Tissues (RELT) is a human Tumor Necrosis Factor
Receptor (TNFR) family member that has two identified homologous binding
partners, RELL1 and RELL2. This study sought to further understand the pattern of
RELT expression, the functional role of RELT family members, and the mechanism of
RELT-induced apoptosis. RELT protein expression was detected in the spleen, lymph
node, brain, breast and peripheral blood leukocytes (PBLs). A smaller than
expected size of RELT was observed in PBLs, suggesting a proteolytically cleaved
form of RELT. RELL1 and RELL2 overexpression activated the p38 MAPK pathway more
substantially than RELT in HEK-293 cells, and this activation of p38 by RELT
family members was blocked by dominant-negative mutant forms of OSR1 or TRAF2,
implicating these molecules in RELT family member signaling. RELT was previously
shown to induce apoptosis in human epithelial cells despite lacking the
characteristic death domain (DD) found in other TNFRs. Seven deletion mutants of
RELT that lacked differing portions of the intracellular domain were created to
assess whether RELT possesses a novel DD. None of the deletion mutants induced
apoptosis as efficiently as full-length RELT, a result that is consistent with a
novel DD being located at the carboxyl-terminus. Interestingly, induction of
apoptotic morphology by RELT overexpression was not prevented when signaling by
FADD or Caspase-8 was blocked, indicating RELT induces apoptosis by a pathway
distinct from other death-inducing TNFRs such as TNFR1. Collectively, this study
provides more insights into RELT expression, RELT family member function, and the
mechanism of RELT-induced death.
PMID- 28688765
TI - CTRP9 regulates hypoxia-mediated human pulmonary artery smooth muscle cell
proliferation, apoptosis and migration via TGF-beta1/ERK1/2 signaling pathway.
AB - Hypoxia is an important risk factor for pulmonary arterial remodeling in
pulmonary arterial hypertension (PAH). Vascular remodeling in hypoxia-induced PAH
is driven by excessive proliferation and migration of pulmonary arterial smooth
muscle cells (PASMCs). The purpose of the present study was to explore the
expression of CTRP9 in rats model of hypoxia-induced PAH and investigate the
effects of CTRP9 on HPASMCs function in vitro and determine the underlying
mechanisms. We established a rat model of hypoxic PAH, which showed a
downregulation of CTRP9 expression. In HPASMCs cultured under the condition of
hypoxia, treatment with CTRP9 notably restrained cell proliferation responses to
hypoxia accompanied with decreased two biomarkers of cell proliferation Ki-67 and
PCNA. Meanwhile, CTRP9 strikingly promoted hypoxia-mediated cell apoptosis as
reflected by upregulation of Bax and downregulation of Bcl-2, as well as enhanced
Caspase 3 activity. Additionally, CTRP9 treatment dramatically prevented the
migratory potential by declined the expression of MMP-2 and MMP-9. Moreover
treatment with CTRP9 augmented hypoxia-mediated differentiation by elevating the
expression level of differentiation markers alpha-SMA and SM22. Mechanistically,
anti-proliferative effects conferred by CTRP9 are mediated through suppression of
TGF-beta1/ERK1/2 pathway. Collectively, we identified CTRP9 as a novel mediator
of PASMC growth in hypoxia-mediated PAH, indicating that CTRP9 in the pulmonary
vasculature may be an underlying mechanism in the development of hypoxia-induced
PAH. Our study, for the first time, established that CTRP9 plays a protective
role of CTRP9 in pulmonary vascular remodeling, pointing to its potential
clinical value for patients with PAH.
PMID- 28688766
TI - Ligands of histamine receptors modulate acid-sensing ion channels.
AB - Recently we found that synthetic compounds containing amino group linked to
hydrophobic or aromatic moiety are potent modulators of the proton-gated channels
(ASICs). These structures have clear similarity with ligands of histamine
receptors. We have also demonstrated that histamine potentiates homomeric ASIC1a
by shifting its activation dependence to less acidic conditions. In the present
work the action of a series of histamine receptors ligands on recombinant ASIC1a
and ASIC2a was characterized. Two types of action were found for ASIC1a. 1
methylhistamine, N-alpha-methylhistamine, dimaprit and thioperamide caused
significant potentiation, which was pH-dependent and voltage-independent. The H4R
antagonist A943931 caused inhibition, which is likely due to voltage-dependent
pore block. ASIC2a were virtually insensitive to the drugs tested. We conclude
that ligands of histamine receptors should also be considered as ASIC modulators.
PMID- 28688767
TI - The activation of B cells enhances DC-SIGN expression and promotes susceptibility
of B cells to HPAI H5N1 infection.
AB - The interplay between highly pathogenic avian influenza (HPAI) H5N1 virus and
immune cells has been extensively studied for years, as host immune components
are thought to play significant roles in promoting the systemic spread of the
virus and responsible for cytokine storm. Previous studies suggested that the
interaction of B cells and monocytes could promote HPAI H5N1 infection by
enhancing avian influenza virus receptor expression. In this study, we further
investigate the relationship between the HPAI H5N1 virus, activated B cells, and
DC-SIGN expression. DC-SIGN has been described as an important factor for
mediating various types of viral infection. Here, we first demonstrate that HPAI
H5N1 infection could induce an activation of B cells, which was associated with
DC-SIGN expression. Using CD40L and recombinant IL-4 for B cell stimulation, we
determined that DC-SIGN expressed on activated B cells was able to enhance its
susceptibility to HPAI H5N1 infection. Our findings uncover the interplay between
this H5N1 virus and B cells and provide important information in understanding
how the virus overcomes our immune system, contributing to its unusual
immunopathogenesis.
PMID- 28688768
TI - The nitroxide 4-methoxy TEMPO inhibits neutrophil-stimulated kinase activation in
H9c2 cardiomyocytes.
AB - After acute myocardial infarction (AMI), neutrophils are recruited to the
affected myocardium. Hypochlorous acid (HOCl) produced by neutrophil
myeloperoxidase (MPO) damages cardiomyocytes and potentially expands the primary
infarct. Rat cardiomyocyte-like cells were incubated with isolated human
neutrophils treated with chemical activators in the absence or presence of
nitroxide 4-methoxy-Tempo (MetT; 25 MUM) for 4, 6 or 24 h; studies with reagent
HOCl served as positive control. Treating cardiomyocytes with activated
neutrophils or reagent HOCl resulted in a marked increase in protein tyrosine
chlorination and a decline in protein tyrosine phosphatase (PTP) activity. On
balance our data also supported an increase in phosphorylation of MAPK p38 and
ERK1/2 suggestive of an intracellular hyperphosphorylation status and this was
accompanied by decreases in cell viability, as judged by assessing caspases-3/7
activity. For cells exposed to activated neutrophils receptor-mediated uptake of
transferrin decreased although total matrix metalloproteinase (MMP) activity was
unaffected. Addition of MetT ameliorated protein tyrosine chlorination, decreased
MAPK activity and restored receptor-mediated transferrin uptake and PTP activity
in cardiomyocytes. Overall, adverse effects of neutrophil-derived HOCl on
cultured cardiomyocytes were ameliorated by MetT suggesting that nitroxides may
be beneficial to inflammatory pathologies, where neutrophil
recruitment/activation is a prominent and early feature.
PMID- 28688769
TI - Revisit, Subsequent Hospitalization, Recurrent Fall, and Death Within 6 Months
After a Fall Among Elderly Emergency Department Patients.
AB - STUDY OBJECTIVE: We seek to describe the risk during 6 months and specific risk
factors for recurrent falls, emergency department (ED) revisits, subsequent
hospitalizations, and death within 6 months after a fall-related ED presentation.
METHODS: This was a secondary analysis of a retrospective cohort of elderly fall
patients who presented to the ED from one urban teaching hospital. We included
patients aged 65 years and older who had an ED fall visit in 2012. We examined
the frequency and risk factors of adverse events (composite of recurrent falls,
ED revisits, subsequent hospitalization, and death, selected a priori) at 6
months. RESULTS: Our study included 350 older adults. Adverse events steadily
increased, from 7.7% at 7 days, 21.4% at 30 days, and 50.3% at 6 months. Within 6
months, 22.6% of patients had at least one recurrent fall, 42.6% revisited the
ED, 31.1% had subsequent hospitalizations, and 2.6% died. In multivariable
logistic regression analysis, psychological or sedative drug use predicted
recurrent falls, ED revisits, subsequent hospitalizations, and adverse events.
CONCLUSION: More than half of fall patients had an adverse event within 6 months
of presenting to the ED after a fall. The risk during 6 months of these adverse
events increased with psychological or sedative drug use. Larger future studies
should confirm this association and investigate methods to minimize recurrent
falls through management of such medications.
PMID- 28688770
TI - Do Corticosteroids Improve Mortality or Shock Reversal in Patients With Septic
Shock?
PMID- 28688771
TI - Optimal Measurement Interval for Emergency Department Crowding Estimation Tools.
AB - STUDY OBJECTIVE: Emergency department (ED) crowding is a barrier to timely care.
Several crowding estimation tools have been developed to facilitate early
identification of and intervention for crowding. Nevertheless, the ideal
frequency is unclear for measuring ED crowding by using these tools. Short
intervals may be resource intensive, whereas long ones may not be suitable for
early identification. Therefore, we aim to assess whether outcomes vary by
measurement interval for 4 crowding estimation tools. METHODS: Our eligible
population included all patients between July 1, 2015, and June 30, 2016, who
were admitted to the JPS Health Network ED, which serves an urban population. We
generated 1-, 2-, 3-, and 4-hour ED crowding scores for each patient, using 4
crowding estimation tools (National Emergency Department Overcrowding Scale
[NEDOCS], Severely Overcrowded, Overcrowded, and Not Overcrowded Estimation Tool
[SONET], Emergency Department Work Index [EDWIN], and ED Occupancy Rate). Our
outcomes of interest included ED length of stay (minutes) and left without being
seen or eloped within 4 hours. We used accelerated failure time models to
estimate interval-specific time ratios and corresponding 95% confidence limits
for length of stay, in which the 1-hour interval was the reference. In addition,
we used binomial regression with a log link to estimate risk ratios (RRs) and
corresponding confidence limit for left without being seen. RESULTS: Our study
population comprised 117,442 patients. The time ratios for length of stay were
similar across intervals for each crowding estimation tool (time ratio=1.37 to
1.30 for NEDOCS, 1.44 to 1.37 for SONET, 1.32 to 1.27 for EDWIN, and 1.28 to 1.23
for ED Occupancy Rate). The RRs of left without being seen differences were also
similar across intervals for each tool (RR=2.92 to 2.56 for NEDOCS, 3.61 to 3.36
for SONET, 2.65 to 2.40 for EDWIN, and 2.44 to 2.14 for ED Occupancy Rate).
CONCLUSION: Our findings suggest limited variation in length of stay or left
without being seen between intervals (1 to 4 hours) regardless of which of the 4
crowding estimation tools were used. Consequently, 4 hours may be a reasonable
interval for assessing crowding with these tools, which could substantially
reduce the burden on ED personnel by requiring less frequent assessment of
crowding.
PMID- 28688772
TI - Is Antiplatelet Therapy an Independent Risk Factor for Traumatic Intracranial
Hemorrhage in Patients With Mild Traumatic Brain Injury?
PMID- 28688773
TI - New vaccination strategies in liver cancer.
PMID- 28688774
TI - Prioritizing the patient voice in the development of urologic oncology research.
AB - Prioritization of patient and stakeholder engagement in the research process has
been realized through increased funding and policy directives at the government
level. Particularly, patient engagement in the preparatory research stage has
driven development of patient-prioritized research questions. In this article, a
successful example of patient-centered research prioritization is reviewed, and
effective strategies and opportunities for patient engagement in urologic
oncology research are described.
PMID- 28688775
TI - Peritoneal encapsulation - an unexpected cause of acute intestinal obstruction.
AB - Peritoneal encapsulation (PE) is a rare congenital anomaly that is formed due to
an accessory peritoneal layer encapsulating the small bowel. Kinking of bowel
within the accessory peritoneal layer or adhesions between the bowel loops and
the peritoneal layer causes symptoms ranging from colicky abdominal pain to
rarely intestinal obstruction. Cleland was the first person to have reported this
condition as early as 1868 and since then only around 30 cases have been
reported. Here, we present a case of acute intestinal obstruction in a 22-year
old woman. Imaging showed dilated bowel loops confined to the centre of the
peritoneal cavity. Intraoperatively it was seen to be a case of peritoneal
encapsulation. The small intestine was freed and accessory layer excised. This
report is to demonstrate this rare congenital anomaly.
PMID- 28688776
TI - Pancreatico-jejunal anastomoses after pancreatoduodenectomy.
PMID- 28688777
TI - The niacin response biomarker as a schizophrenia endophenotype: A status update.
AB - Increasingly, it is recognized that the behavioral syndrome of schizophrenia is
not a unitary disease with a single underlying cause. Rather, it may have several
possible etiologies, and its symptoms may arise from multiple causes. Such
heterogeneity could account for some of the difficulties in elucidating its
genetics, and may also explain clinical observations of variable medication
response in schizophrenia. The ability to categorize schizophrenia using
objectively recognizable, physiologically-based subtypes promises to make our
understanding of schizophrenia more comprehensive and could provide some clues
for more personalized treatment. This paper will review the extent to which an
abnormally blunted skin flush response to niacin satisfies the criteria for a
schizophrenia endophenotype.
PMID- 28688778
TI - Production of a broad-specificity monoclonal antibody and application as a
receptor to detection amatoxins in mushroom.
AB - In this study, we report the production of a monoclonal broad-specificity
monoclonal antibody (mAb) specific for amatoxins and development of an indirect
competitive immunoassay for detection of amatoxins in mushroom samples. In the
assay, the complete antigen (alpha-amanitin-OVA) was used as coating antigen, and
amatoxins as competitor competes with coating antigen to bind with mAb. Using
this approach, The half-maximum inhibition concentrations (IC50) of alpha
amanitin, beta-amanitin and gamma-amanitin, and limits of detection (LODs, IC15)
were 66.3, 97.4, 163.1 ng/mL and 0.91, 0.98, 0.89 ng/mL, respectively. The LODs
for alpha-amanitin, beta-amanitin and gamma-amanitin in mushroom samples were
4.55, 4.9, and 4.45 ng/mL. The spiked results were also confirmed by HPLC, which
showed a good correlation (R2 = 0.996) between the two methods. The results
indicated that the developed assay was reliable and suitable for the detection of
amatoxins in mushroom samples.
PMID- 28688779
TI - Formulation, stabilisation and encapsulation of bacteriophage for phage therapy.
AB - Against a backdrop of global antibiotic resistance and increasing awareness of
the importance of the human microbiota, there has been resurgent interest in the
potential use of bacteriophages for therapeutic purposes, known as phage therapy.
A number of phage therapy phase I and II clinical trials have concluded, and
shown phages don't present significant adverse safety concerns. These clinical
trials used simple phage suspensions without any formulation and phage stability
was of secondary concern. Phages have a limited stability in solution, and
undergo a significant drop in phage titre during processing and storage which is
unacceptable if phages are to become regulated pharmaceuticals, where stable
dosage and well defined pharmacokinetics and pharmacodynamics are de rigueur.
Animal studies have shown that the efficacy of phage therapy outcomes depend on
the phage concentration (i.e. the dose) delivered at the site of infection, and
their ability to target and kill bacteria, arresting bacterial growth and
clearing the infection. In addition, in vitro and animal studies have shown the
importance of using phage cocktails rather than single phage preparations to
achieve better therapy outcomes. The in vivo reduction of phage concentration due
to interactions with host antibodies or other clearance mechanisms may
necessitate repeated dosing of phages, or sustained release approaches. Modelling
of phage-bacterium population dynamics reinforces these points. Surprisingly
little attention has been devoted to the effect of formulation on phage therapy
outcomes, given the need for phage cocktails, where each phage within a cocktail
may require significantly different formulation to retain a high enough infective
dose. This review firstly looks at the clinical needs and challenges (informed
through a review of key animal studies evaluating phage therapy) associated with
treatment of acute and chronic infections and the drivers for phage
encapsulation. An important driver for formulation and encapsulation is shelf
life and storage of phage to ensure reproducible dosages. Other drivers include
formulation of phage for encapsulation in micro- and nanoparticles for effective
delivery, encapsulation in stimuli responsive systems for triggered controlled or
sustained release at the targeted site of infection. Encapsulation of phage (e.g.
in liposomes) may also be used to increase the circulation time of phage for
treating systemic infections, for prophylactic treatment or to treat
intracellular infections. We then proceed to document approaches used in the
published literature on the formulation and stabilisation of phage for storage
and encapsulation of bacteriophage in micro- and nanostructured materials using
freeze drying (lyophilization), spray drying, in emulsions e.g. ointments,
polymeric microparticles, nanoparticles and liposomes. As phage therapy moves
forward towards Phase III clinical trials, the review concludes by looking at
promising new approaches for micro- and nanoencapsulation of phages and how these
may address gaps in the field.
PMID- 28688780
TI - Relationship between processing history and functionality recovery after
rehydration of dried cellulose-based suspensions: A critical review.
AB - Cellulose-based suspensions have raised more and more attention due to their
broad range of properties that can be used in paper industry and material science
but also in medicine, nanotechnology and food science. Their final functionality
is largely dependent on their processing history and notably the structural
modifications that occur during drying and rehydration. The purpose of this work
is to make a state-of-the-art contribution to the mechanisms involved in the
process-structure-function relationships of cellulose-based hydrogels. The
different assumptions that exist in the literature are reviewed taking the key
role of the initial sample characteristics as well as the processing conditions
into consideration. The decrease in swelling ability after drying is clearly due
to an overall shrinkage of the structure of the material. At microscale, pore
closure and cellulosic fibril aggregation are mentioned as the main reasons. The
origins of such irreversible structural modifications take place at molecular
level and is mainly explained by the establishment of a new balance of
interactions between all components. Nevertheless, the respective contribution of
each interaction are still under investigation.
PMID- 28688781
TI - Immunogenicity of 13-valent pneumococcal conjugate vaccine among children with
underlying medical conditions.
AB - BACKGROUND: Streptococcus pneumoniae is a leading cause of vaccine-preventable
disease in children under 5years. Immunocompromised children and those with
underlying diseases are at increased risk of severe complications from vaccine
preventable infections. We studied the humoral immune response to the 13-valent
pneumococcal conjugate vaccine (PCV13) in children with HIV-infection, kidney or
lung disease and compared this to the response in healthy control children.
METHODS: Children aged 12-71months with underlying conditions including HIV
infection and those with kidney and lung diseases (at-risk children), and a
healthy control group were vaccinated with PCV13. The at-risk children received
two doses of PCV13 and the controls received one dose. Serotype-specific
antibodies for all PCV13 serotypes were measured by a luminex-based enzyme
immunoassay at baseline and post-vaccination. RESULTS: After the first PCV13
dose, the fold-increase in serotype-specific antibody geometric mean
concentrations (GMCs) from baseline and the percentage of participants with >=4
fold-increase in antibody concentrations was similar between the control and at
risk children. GMCs were, however, lower for three of the 13 serotypes in HIV
infected children, higher for serotype 6B in children with kidney disease and
higher for serotypes 6B and 14 in children with lung disease. After second
vaccine dose HIV-infected children had an increase in GMCs from post-first dose
for nine serotypes but the percentage of participants with >=4-fold-increase from
baseline was similar post-second dose compared to post-first dose except for
serotypes 6A and 19F. In children with kidney or lung diseases the immune
responses after second vaccine dose were similar to post-first dose. Attenuated
responses were observed for serotypes 3 and 19A in all study-groups, which was
especially pronounced in the at-risk groups. CONCLUSION: All study-groups mounted
an immune response to PCV13, with the at-risk groups having responses that were
mostly similar to the control children.
PMID- 28688782
TI - A single center, open label study of intradermal administration of an inactivated
purified chick embryo cell culture rabies virus vaccine in adults.
AB - In the USA, rabies vaccines (RVs) are licensed for intramuscular (IM) use only,
although RVs are licensed for use by the intradermal (ID) route in many other
countries. Recent limitations in supplies of RV in the USA reopened discussions
on the more efficient use of available biologics, including utilization of more
stringent risk assessments, and potential ID RV administration. A clinical trial
was designed to compare the immunogenic and adverse effects of a purified chicken
embryo cell (PCEC) RV administered ID or IM. Enrollment was designed in four
arms, ID Pre-Exposure Prophylaxis (Pre-EP), IM Pre-EP, ID Booster, and IM Booster
vaccination. Enrollment included 130 adult volunteers. The arms with IM
administration received vaccine according to the current ACIP recommendations:
Pre-EP, three 1mL (2.5 I.U.) RV doses, each on day 0, 7, and 21; or a routine
Booster, one 1ml dose. The ID groups received the same schedule, but doses
administered were in a volume of 0.1mL (0.25 I.U.). The rate of increase in
rabies virus neutralizing antibody titers 14-21days after vaccination were
similar in the ID and correspondent IM groups. The GMT values for ID vaccination
were slightly lower than those for IM vaccination, for both naive and booster
groups, and these differences were statistically significant by t-test. Fourteen
days after completing vaccination, all individuals developed RV neutralizing
antibody titers over the minimum arbitrary value obtained with the rapid
fluorescent focus inhibition test (RFFIT). Antibodies were over the set threshold
until the end of the trial, 160days after completed vaccination. No serious
adverse reactions were reported. Most frequent adverse reactions were erythema,
induration and tenderness, localized at the site of injection. Multi use of 1mL
rabies vaccine vials for ID doses of 0.1 was demonstrated to be both safe and
inmunogenic.
PMID- 28688783
TI - Vaccine opponents' use of Twitter during the 2016 US presidential election:
Implications for practice and policy.
PMID- 28688784
TI - Improving hepatitis B birth dose coverage through village health volunteer
training and pregnant women education.
AB - Hepatitis B is highly endemic in the Republic of Kiribati, while the coverage of
timely birth dose vaccination, the primary method shown to prevent mother-to
child transmission of hepatitis B virus, was only 66% in 2014. Children born at
home are especially at high risk, as they have limited access to timely birth
dose (i.e. within 24 h) vaccination. To improve birth dose coverage, a project to
improve linkages between village health volunteers and health workers and educate
pregnant women on hepatitis B vaccination was carried out in 16 communities with
low birth dose coverage in Kiribati from November 2014 to May 2015. After project
completion, the coverage of timely birth dose administration increased
significantly both in the densely populated capital region of South Tarawa (from
89% to 95%, p=0.001) and the Outer Islands (from 57% to 83%, p<0.001). The
coverage of timely birth dose administration among infants born at home increased
significantly from 70% to 84% in South Tarawa (p=0.001) and from 49% to 75% in
the Outer Islands (p<0.001). Timely birth dose was associated with being born in
a hospital, being born during the study period and caregivers having developed an
antenatal birth dose plan. The project demonstrates a successful model for
improving hepatitis B vaccine birth dose coverage that could be adopted in other
areas in Kiribati as well as other similar settings.
PMID- 28688786
TI - Perception of Barriers to the Diagnosis and Receipt of Treatment for
Neuropsychiatric Disturbances After Traumatic Brain Injury.
AB - OBJECTIVE: To explore perceptions of barriers and facilitators to the diagnosis
and receipt of treatment for neuropsychiatric disturbances (NPDs) after traumatic
brain injury (TBI). DESIGN: Qualitative study using semistructured interviews and
focus groups. SETTING: A clinic specializing in the treatment of TBI NPDs, an
urban trauma center, and a large urban academic hospital. PARTICIPANTS: A sample
(N=33) of health care providers (n=10) who treat individuals with TBI, persons
with TBI (n=18), and caregivers (n=5). INTERVENTIONS: Not applicable. MAIN
OUTCOME MEASURES: Topic guides for the interviews and focus groups were guided by
previous literature, clinical experience, and the goals of the project and
focused on the 3 most common TBI NPDs: depression, anxiety, and posttraumatic
stress disorder. The interviews and focus groups were audio-recorded and
transcribed verbatim. We performed a conventional content analysis on the
transcripts and grouped concepts into overall themes, incorporating feedback from
stakeholders. RESULTS: Patient education, insurance, provider type, time since
TBI, caregiver support, and recognition or screening for TBI NPDs were the most
frequently mentioned barriers or facilitators to the diagnosis and treatment of
TBI NPDs by both interview and focus group participants. We grouped these and
other frequently mentioned concepts into 3 broad themes: education, access, and
support. Each of these themes is explored in depth and supported with direct
quotations. CONCLUSIONS: This study explored patient, caregiver, and health care
provider and identified barriers and facilitators to the diagnosis and receipt of
treatment for TBI NPDs. Barriers included poor provider education on TBI NPDs and
limited access to care due to lack of insurance, transportation, and income.
Facilitators included patient education on TBI NPDs and strong caregiver support.
Future studies should develop and pilot interventions aimed at quality of care
that address the identified barriers and facilitators.
PMID- 28688785
TI - A single dose of the novel chimeric subunit vaccine E2-CD154 confers early full
protection against classical swine fever virus.
AB - Classical swine fever is an economically important, highly contagious disease of
swine worldwide. Subunit vaccines are a suitable alternative for the control of
classical swine fever. However, such vaccines have as the main drawback the
relatively long period of time required to induce a protective response, which
hampers their use under outbreak conditions. In this work, a lentivirus-based
gene delivery system is used to obtain a stable recombinant HEK 293 cell line for
the expression of E2-CSFV antigen fused to porcine CD154 as immunostimulant
molecule. The E2-CD154 chimeric protein was secreted into the medium by HEK293
cells in a concentration around 50mg/L in suspension culture conditions using
spinner bottles. The E2-CD154 immunized animals were able to overcome the
challenge with a high virulent CSF virus strain performed 7days after a unique
dose of the vaccine without clinical manifestations of the disease. Specific anti
CSFV neutralizing antibodies and IFN-gamma were induced 8days after challenge
equivalent to 14days post-vaccination. The present work constitutes the first
report of a subunit vaccine able to confer complete protection by the end of the
first week after a single vaccination. These results suggest that the E2-CD154
antigen could be potentially used under outbreak conditions to stop CSFV spread
and for eradication programs in CSF enzootic areas.
PMID- 28688787
TI - Retrospective Analysis of Predictors of Proficient Power Mobility in Young
Children With Severe Motor Impairments.
AB - OBJECTIVES: To determine if child characteristics, maternal education,
intervention parameters, type of wheelchair control mechanism, or a combination
of these variables were associated with proficient power mobility skills in
children with severe motor impairments aged 14 to 30 months; and to determine if
performance on the Wheelchair Skills Checklist (WSC) was associated with
performance on the Powered Mobility Program (PMP). DESIGN: Secondary data
analyses on data collected from 2 previously completed randomized controlled
trials (RCTs). SETTING: Intervention and outcomes measurements took place in
natural environments. PARTICIPANTS: Participants included children who were
assigned to the intervention groups in 2 RCTs (N=31). INTERVENTION: Children
practiced maneuvering individually customized power wheelchairs for 12 months in
natural environments. MAIN OUTCOME MEASURES: Proficiency was assessed using the
WSC and the PMP. The Battelle Developmental Inventory and Merrill-Palmer-Revised
were used to assess baseline cognition and motor skills. Baseline mobility was
assessed using the Pediatric Evaluation of Disability Inventory. RESULTS:
Cognition, fine motor skills, and wheelchair control mechanism were associated
with proficiency. Cognition, type of wheelchair control, and diagnosis all
predicted proficiency while controlling for other covariates using multiple
regression analysis. Agreement between the WSC and PMP was 94.7%. CONCLUSIONS:
Cognition, type of wheelchair control, and diagnosis might predict power mobility
proficiency in young children with severe motor impairments. These factors
however should not be used to determine whether a child has the opportunity to
participate in a training program. Agreement between the WSC and PMP could help
researchers and clinicians compare results across studies that use only one of
these outcome measures.
PMID- 28688788
TI - Letter Reply.
PMID- 28688789
TI - Yoga Treatment for Chronic Non-Specific Low Back Pain (2017).
AB - : Wieland LS, Skoetz N, Pilkington K, Vempati R, D'Adamo CR, Berman BM. Yoga
treatment for chronic non-specific low back pain.Cochrane Database Syst Rev2017,
Issue 1. Art. No.: CD010671. DOI: 10.1002/14651858.CD010671.pub2. BACKGROUND: Non
specific low back pain is a common, potentially disabling condition usually
treated with self-care and non-prescription medication. For chronic low back
pain, current guidelines state that exercise therapy may be beneficial. Yoga is a
mind-body exercise sometimes used for non-specific low back pain. OBJECTIVES: To
assess the effects of yoga for treating chronic non-specific low back pain,
compared to no specific treatment, a minimal intervention (e.g., education), or
another active treatment, with a focus on pain, function, and adverse events.
SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, five other databases, and
four trials registers to 11 March 2016 without restriction of language or
publication status. We screened reference lists and contacted experts in the
field to identify additional studies. SELECTION CRITERIA: We included randomized
controlled trials of yoga treatment in people with chronic non-specific low back
pain. We included studies comparing yoga to any other intervention or to no
intervention. We also included studies comparing yoga as an adjunct to other
therapies, versus those other therapies alone. DATA COLLECTION AND ANALYSIS: Two
authors independently screened and selected studies, extracted outcome data, and
assessed risk of bias. We contacted study authors to obtain missing or unclear
information. We evaluated the overall certainty of evidence using the GRADE
approach. MAIN RESULTS: We included 12 trials (1080 participants) carried out in
the USA (seven trials), India (three trials), and the UK (two trials). Studies
were unfunded (one trial), funded by a yoga institution (one trial), funded by
non-profit or government sources (seven trials), or did not report on funding
(three trials). Most trials used Iyengar, Hatha, or Viniyoga forms of yoga. The
trials compared yoga to no intervention or a non-exercise intervention such as
education (seven trials), an exercise intervention (three trials), or both
exercise and non-exercise interventions (two trials). All trials were at high
risk of performance and detection bias because participants and providers were
not blinded to treatment assignment, and outcomes were self-assessed. Therefore,
we downgraded all outcomes to "moderate" certainty evidence because of risk of
bias, and when there was additional serious risk of bias, unexplained
heterogeneity between studies, or the analyses were imprecise, we downgraded the
certainty of the evidence further. For yoga compared to non-exercise controls (9
trials; 810 participants), there was low-certainty evidence that yoga produced
small to moderate improvements in back-related function at three to four months
[standardized mean difference (SMD) = -0.40, 95% CI: -0.66 to -0.14;
corresponding to a change in the Roland-Morris Disability Questionnaire of mean
difference (MD) = -2.18, 95% CI: -3.60 to -0.76], moderate-certainty evidence for
small to moderate improvements at six months (SMD = -0.44, 95% CI: -0.66 to
0.22; corresponding to a change in the Roland-Morris Disability Questionnaire of
MD = -2.15, 95% CI: -3.23 to -1.08), and low-certainty evidence for small
improvements at 12 months (SMD = -0.26, 95% CI: -0.46 to -0.05; corresponding to
a change in the Roland-Morris Disability Questionnaire of MD = -1.36, 95% CI:
2.41 to -0.26). On a 0-100 scale there was very low- to moderate-certainty
evidence that yoga was slightly better for pain at three to four months (MD =
4.55, 95% CI: -7.04 to -2.06), six months (MD = -7.81, 95% CI: -13.37 to -2.25),
and 12 months (MD = -5.40, 95% CI: -14.50 to -3.70); however, we pre-defined
clinically significant changes in pain as 15 points or greater and this threshold
was not met. Based on information from six trials, there was moderate-certainty
evidence that the risk of adverse events, primarily increased back pain, was
higher in yoga than in non-exercise controls [risk difference (RD) = 5%, 95% CI:
2-8%]. For yoga compared to non-yoga exercise controls (4 trials; 394
participants), there was very-low-certainty evidence for little or no difference
in back-related function at three months (SMD = -0.22, 95% CI: -0.65 to 0.20;
corresponding to a change in the Roland-Morris Disability Questionnaire of MD =
0.99, 95% CI: -2.87 to 0.90) and six months (SMD = -0.20, 95% CI: -0.59 to 0.19;
corresponding to a change in the Roland-Morris Disability Questionnaire of MD =
0.90, 95% CI: -2.61 to 0.81), and no information on back-related function after
six months. There was very low-certainty evidence for lower pain on a 0-100 scale
at seven months (MD = -20.40, 95% CI: -25.48 to -15.32), and no information on
pain at three months or after seven months. Based on information from three
trials, there was low-certainty evidence for no difference in the risk of adverse
events between yoga and non-yoga exercise controls (RD = 1%, 95% CI: -4% to 6%).
For yoga added to exercise compared to exercise alone (1 trial; 24 participants),
there was very-low-certainty evidence for little or no difference at 10 weeks in
back-related function (SMD = -0.60, 95% CI: -1.42 to 0.22; corresponding to a
change in the Oswestry Disability Index of MD = -17.05, 95% CI: -22.96 to 11.14)
or pain on a 0-100 scale (MD = -3.20, 95% CI: -13.76 to 7.36). There was no
information on outcomes at other time points. There was no information on adverse
events. Studies provided limited evidence on risk of clinical improvement,
measures of quality of life, and depression. There was no evidence on work
related disability.
PMID- 28688790
TI - [Human albinism].
PMID- 28688791
TI - Perinatal and social factors predicting caesarean birth in a 2004 Australian
birth cohort.
AB - BACKGROUND: The proportion of babies born by caesarean section in Australia has
almost doubled over the last 25 years. Factors known to contribute to caesarean
such as higher maternal age, mothers being overweight or obese, or having had a
previous caesarean do not completely account for the increased rate and it is
clear that other influences exist. AIM: To identify previously unsuspected risk
factors associated with caesarean using nationally-representative data from the
Longitudinal Study of Australian Children. METHODS: Data were from the birth
cohort, a long-term prospective study of approximately 5000 children that
includes richly-detailed data regarding maternal health and exposures during
pregnancy. Logistic regression was used to examine the contribution of a wide
range of pregnancy, birth and social factors to caesarean. FINDINGS: 28% of 4862
mothers were delivered by caesarean. The final adjusted analyses revealed that
use of diabetes medication (OR=3.1, 95% CI=1.7-5.5, p<0.001) and maternal mental
health problems during pregnancy (OR=1.3, CI=1.1-1.6, p=0.003) were associated
with increased odds of caesarean. Young maternal age (OR=0.6, CI=0.5-0.7,
p<0.001), having two or more children (OR=0.7, CI=0.6-0.9, p<0.001), and fathers
having an unskilled occupation (OR=0.7, CI=0.6-1.0, p=0.036) were associated with
reduced odds of caesarean. CONCLUSION: Our findings raise the prospect that the
effect of additional screening and support for maternal mental health on
caesarean rate should be subject of prospective study.
PMID- 28688792
TI - Risk factors for transcervical incision and drainage of pediatric deep neck
infections.
AB - OBJECTIVES: The aim of this study was to identify risk factors for transcervical
approaches in the treatment of pediatric deep neck infections (DNIs). METHODS: We
performed a retrospective analysis of data from patients who were diagnosed with
DNIs. All medical records were reviewed for demographic characteristics,
presenting signs and symptoms, duration of symptoms, size of abscess, laboratory
results, duration of intravenous (IV) antibiotic administration, duration of
hospitalization, medical treatment, and type of surgical drainage (oral or
transcervical approach). We divided 126 patients into three groups according to
the approach used to treat the DNI: non-surgical, intraoral surgical and external
transcervical surgical. RESULTS: The average ages of the non-surgical, intraoral,
and transcervical groups were 10.46+/-5.27, 12.75+/-4.82 and 5.54+/-5.15years,
respectively. The transcervical approach was used to treat younger patients
(p<0.001). Abscess size was significantly larger for the transcervical group
compared to the other groups (5.72+/-8.93, 13.51+/-14.74, 18.36+/-16.05mm, non
surgical, intraoral, and transcervical group, respectively, p=0.009). The average
duration of IV antibiotic administration for the transcervical group was 9.77+/
3.27days, which was significantly higher than those for the other groups (5.49+/
3.28 for non-surgical and 6.13+/-2.85 for intraoral, p<0.001). Multivariate
analysis revealed that submandibular abscesses (Exp (B)=5.254, p=0.012) were the
only significant risk factor for the transcervical approach in surgical treatment
of DNIs. CONCLUSION: Submandibular space abscesses were the only significant risk
factor for the transcervical approach in the treatment of pediatric DNI patients.
LEVEL OF EVIDENCE: III.
PMID- 28688793
TI - Separation of pygopagus, omphalopagus, and ischiopagus with the aid of three
dimensional models.
AB - BACKGROUND: The three-dimensional (3D) technique provides with accurate
anatomical information. We present the separation surgeries for three different
kinds of conjoined twins with the aid of three-dimensional techniques. METHOD:
For the pygopagus twins, a pelvic and lower vertebral model was made. For the
omphalopagus and ischiopagus, their enhanced computed tomography (CT) scan images
were transferred to the Computer-Assisted Surgery Planning System (CASP)
(Hisense, Qingdao, China) to generate the 3D models. RESULT: In the case of the
pygopagus twins, the 3D model clearly showed that their coccyges were joined at a
120 degrees angle from each other horizontally which suggested that the blind-end
orifice on their back was a pilonidal sinus, which separated the normal sphincter
into two halves. In the omphalopagus, the 3D model revealed one of the branches
of each twin's hepatic vein was connected with the other's. The 3D model of the
ischiopagus twins revealed that both of the twins had duplicated bladders and
each baby's duplicated bladders united with one of the bladders of the other baby
and a single rectum passing through the middle of the four bladders. CONCLUSION:
3D techniques could provide more detailed anatomical information, which is
helpful in planning procedures for such complicated separation surgery. LEVELS OF
EVIDENCE: Level IV.
PMID- 28688794
TI - Transition of care in patients with anorectal malformations: Consensus by the ARM
net consortium.
AB - OBJECTIVES: To develop the first consensus to standardize the management of
patients with Anorectal Malformations (ARMs) transitioning from childhood to
adulthood. METHODS: A dedicated task force of experts performed an extensive
literature review and multiple meetings to define the most important aspects of
transition of care. The findings were discussed with all ARM-net consortium
members and a set of practical recommendations agreed upon at the annual meeting
in 2016. RESULT: We defined seven domains that are essential to provide an
effective and practical transition process. Within each domain we have developed
a set of key recommendations that are important to be considered for ARM patients
entering the age of transition. CONCLUSIONS: It is crucial that transition begins
at an early age with regular and well-structured follow-up. Cooperation with a
selected multidisciplinary team of pediatric and adult practitioners is required
to prepare patients and families for effective transition to adult care and to
reduce long term morbidity. TYPE OF STUDY: Review/Consensus paper. LEVEL OF
EVIDENCE: III.
PMID- 28688795
TI - GPER1 in sand rat epididymis: Effects of seasonal variations, castration and
efferent ducts ligation.
AB - Estrogen plays a crucial role in regulating epididymal function and development.
Estrogen signaling is mediated via two main receptors essentially involved in the
genomic regulating pathway: ERalpha and ERbeta. Recent studies revealed the
contribution of a novel estrogen receptor involved in the non-genomic pathway:
GPER1. This receptor belongs to the family of seven-transmembrane G-protein
coupled receptors and it triggers rapid cellular responses. Immuno-histochemical
studies and Western Blot analyses were performed to investigate the GPER1
expression in the caput and cauda epididymis of free-ranging fat sand rats
(Psammomys obesus) captured during the breeding and resting seasons. We also
investigated the effect of castration (C), castration followed by testosterone
treatment (C+T), and ligation of the efferent ducts (L). During the breeding
season, a marked positive GPER1 immunoreactivity was detected in the cytoplasm of
principal cells and basal cells; this signal persisted during the resting season,
attenuated however, meanwhile the clear cells were not immuno-reactive. In C
animals, the immuno-histochemical staining underwent nuclear translocation. In
C+T animals, this response became nuclear and cytoplasmic. In the L group, the
expression of the GPER1 was mainly located in the cytoplasm of principal cells
and in the nuclei of basal cells; the sperm was also immune-positive in the cauda
epididymis. Western blot analysis showed that GPER1 has a molecular weight of
55kDa in the caput and cauda epididymis during the breeding season, and it
persisted during the resting season in the caput epididymis with a decrease in
the cauda epididymis. These results suggest that GPER1 mediate a specific
cellular estrogen signaling with marked differences between the breeding and
resting seasons. Experimental groups suggest that testosterone is involved in the
regulation of the expression of GPER1, in addition to other estrogen
signalization pathways.
PMID- 28688796
TI - Fatty acid-based lipidomics and membrane remodeling induced by apoE3 and apoE4 in
human neuroblastoma cells.
AB - Apolipoprotein E (apoE) is a major lipid carrier of the lipoprotein transport
system that plays critical roles in various pathologies. Human apoE has three
common isoforms, the apoE4 being associated with Alzheimer's disease. This is the
first study in the literature investigating the effects of apoE (apoE3 and apoE4
isoforms) on membrane fatty acid profile in neuroblastoma SK-N-SH cells. Fatty
acid analyses were carried out by gas chromatography of the corresponding methyl
esters (FAME). We observed the occurrence of membrane fatty acid remodeling in
the presence of each of the two apoE isoforms. ApoE3 increased the membrane level
of stearic acid and dihomo-gamma-linolenic acid (DGLA), whereas apoE4 had
opposite effects. Both apoE3 and apoE4 increased saturated and monounsaturated
fatty acids (SFA and MUFA), omega-6/omega-3 ratio and decreased total
polyunsaturated fatty acid (PUFA) amount, but with various intensities. Moreover,
both apoE isoforms decreased membrane homeostasis indexes such as PUFA balance,
unsaturation index and peroxidation index. Our results highlight membrane
property changes connected to the apoE isoforms suggesting membrane lipidomics to
be inserted in further model studies of apolipoproteins in health and disease.
PMID- 28688797
TI - Burden of traffic accidents among pedestrians of Fars province, southern Iran;
estimate of years of life lost in a sample of Iranian population from 2009 to
2013.
AB - PURPOSE: Traffic injuries are among the leading causes of mortality and morbidity
worldwide. Pedestrians have been considered as a high-risk group among road
users, especially in middle- or low-income communities. This study attempted to
determine the burden of pedestrians' fatalities in Fars, the southern province of
Iran using years of life lost (YLL) approach. METHODS: The data used in this
study were retrieved from Fars Forensic Medicine Organization database on
pedestrian traffic accidents. The YLL from 2009 to 2013 was estimated using the
method presented by World Health organization. Some epidemiological
characteristics of pedestrians' fatalities were analyzed by SPSS. RESULTS:
Although YLL among 1000 male pedestrians decreased from 2.5 in 2009 to 1.5 in
2013, it increased from 0.9 to 2.1 among 1000 females during the same period.
Higher proportion of death was found in female, illiterate, and married
pedestrians (p < 0.001). In addition, mortality was higher in pedestrians living
the cities, during daytime, at home, and in hospitals (p < 0.001). CONCLUSION:
Consistent with the global trends, burden of pedestrian accidents in Fars was
also exceptionally high. Considering the national and cultural aspects of
different countries, improving the safety of pedestrians demands a multi
dimensional approach with interventional factors concerning policies, rules,
pedestrians, motor vehicles and environmental conditions taken into
consideration.
PMID- 28688798
TI - Place of the reposition flap in the treatment of distal amputations of the
fingers.
AB - PURPOSE: Distal finger amputations pose a therapeutic problem with the distal
fragment quality. Reimplantation remains the reference treatment for functional
and aesthetic recovery of the hand. The interest of this study is to propose the
reposition flap as an alternative to different hedging techniques in the proximal
stump, in many situations where revascularization is impossible. It consists in
osteosynthesis of the bone fragment and its coverage by a pedicled local flap.
METHODS: The technique of reposition flap was evaluated retrospectively between
2003 and 2016 through a study of 13 patients compiled in Nabeul orthopedic
department. For each patient, the sensitivity, the pulp trophicity, the
interphalangeal mobility, the digital length, the appearance of the nail and
radiological consolidation were evaluated. RESULTS: The reposition flap keeps
more than 80% of the length of p3. This procedure improves nail aesthetics in
comparison with the regularizations. There is no significant difference in
sensitivity of the pulp or of the mobility of the distal inter-phalangeal (DIP)
joint as a function of the technique studied. However there is a significant
difference in average test of the Quick Dash (350 against 500 for
regularizations). CONCLUSION: The reposition flap seems to be a good alternative
to regularization in the context of trans-p3 fingers amputations, in which the
distal fragment is not revascularizable. It allows better aesthetic and
functional results.
PMID- 28688799
TI - Trephination mini-craniectomy for traumatic posterior fossa epidural hematomas in
selected pediatric patients.
AB - PURPOSE: Posterior fossa epidural hematomas (PFEDH) are uncommon in children but
usually require timely surgical intervention due to the risk of life-threatening
brainstem compression. We attempt to make the surgical procedure less invasive by
treating selected pediatric patients with trephination mini-craniectomy. METHODS:
We retrospectively reviewed the clinical courses, radiological findings, surgical
procedures, and prognoses of the pediatric patients who were treated in our
departments for traumatic PFEDH from January 2010 to January 2015. RESULTS:
During this period, a total of 17 patients were surgically treated for PFEDH and
7 were managed with trephination mini-craniectomy for hematoma evacuation. The
outcomes were good in all 7 patients as evaluated with Glasgow Outcome Score.
There was no mortality in this series. The on average 30-month clinical follow-up
showed that patients experienced satisfactory recoveries without complications.
CONCLUSION: Our results suggest that trephination mini-craniectomy is a safe
surgical technique for selected PFEDH patients with moderate hematoma volume and
stabilized neurological functions. However, standard craniectomy is recommend
when there are rapid deteriorations in patients' neurological functions or the
hematomas are large and exerted severe mass effects.
PMID- 28688801
TI - New-onset hemodialysis-related headache presenting as migraine aura.
AB - Hemodialysis headache (HDH) is an infrequent new-onset symptom, occurring mainly
in old uremic patients. Type of pain is nonspecific, occurs during hemodialysis
treatment, assuming features similar to tension-type headache and representing a
problem, also as regards the therapy to be taken. International Headache Society
(IHS) has placed this form of headache among the headaches disorders of
homeostasis. We found a case of new-onset HDH in old uremic man, presenting with
migraine aura features. A similar case has not been reported in literature,
placing us some questions: why and how does this happen? What are the mechanisms
involved? Role of trigeminal-vascular system and cortical spreading depression as
regards the aura could be considered, through the activation of neuroinflammatory
events, lastly causing migraine aura. Moreover, the administration of flunarizine
strongly improved migraine symptoms in our patient, as happens in migraine
syndromes. Definitely, this case leads us to think that some mechanisms involved
in headaches will need to be further clarified.
PMID- 28688800
TI - Protein Degradation Systems as Antimalarial Therapeutic Targets.
AB - Artemisinin (ART)-based combination therapies are the most efficacious treatment
of uncomplicated Plasmodium falciparum malaria. Alarmingly, P. falciparum strains
have acquired resistance to ART across much of Southeast Asia. ART creates
widespread protein and lipid damage inside intraerythrocytic parasites,
necessitating macromolecule degradation. The proteasome is the main engine of
Plasmodium protein degradation. Indeed, proteasome inhibition and ART have shown
synergy in ART-resistant parasites. Moreover, ubiquitin modification is
associated with altered parasite susceptibility to multiple antimalarials.
Targeting the ubiquitin-proteasome system (UPS), therefore, is an attractive
avenue to combat drug resistance. Here, we review recent advances leading to
specific targeting of the Plasmodium proteasome. We also highlight the potential
for targeting other nonproteasomal protein degradation systems as an additional
strategy to disrupt protein homeostasis.
PMID- 28688802
TI - Reply to: "Serum metabolic signatures in patients with overt hepatic
encephalopathy": Metabolic signature for severe cirrhosis with inflammation or
hepatic encephalopathy: Do we really face two different entities?
PMID- 28688803
TI - Hyaluronidase-like enzymes are a frequent component of venoms from theraphosid
spiders.
AB - Theraphosid spider venoms are extremely complex mixtures, composed mainly by low
molecular compounds, peptides, and enzymes. The large size of these spiders and
their ability to breed in captivity permits access to rather large amounts of
venom and an easier venom extraction. In the present study, we conducted a
comparative investigation about the content of hyaluronidase-like enzymes in the
venoms from several theraphosid spiders, with a special focus on the
Poecilotheria species, which are considered as underestimated theraphosids of
medical importance. The following species were analyzed: Poecilotheria regalis,
Poecilotheria ornata, Poecilotheria rufilata, Poecilotheria vittata, Bonnetina
papalutlensis, Aphonopelma sp., Brachypelma smithi, Brachypelma epicureanum,
Brachypelma boehmei, Grammostola porteri, Lasiodora klugi, Ceratogyrus darlingi,
and Nhandu chromatus. The presence of hyaluronidase-like enzymes was evidenced in
all venoms by a turbidimetric method and zymography. Several isoforms of acid
active hyaluronidase-like enzymes were detected in the venoms from Poecilotheria
species. These results provide some biochemical characteristics of the high
molecular mass proteins of the theraphosid venoms.
PMID- 28688804
TI - Crotoxin, a rattlesnake toxin, down-modulates functions of bone marrow
neutrophils and impairs the Syk-GTPase pathway.
AB - Neutrophils have a critical role in the innate immune response; these cells
represent the primary line of defense against invading pathogens or tissue
injury. Crotoxin (CTX), the major toxin of the South American rattlesnake
(Crotalus durissus terrificus) venom, presents longstanding anti-inflammatory
properties, inhibiting neutrophil migration and phagocytosis by peritoneal
neutrophils for 14 days. Herein, to elucidate these sustained inhibitory effects
induced by CTX, we performed in vitro and in vivo studies evaluating the
functionality of bone marrow neutrophils and possible molecular mechanisms
associated with these effects. CTX inhibited the processes of chemotaxis,
adhesion to fibronectin, and phagocytosis of opsonized particles; however, it did
not affect ROS production or degranulation in bone marrow neutrophils. To
understand the molecular mechanisms that orchestrate this effect, we investigated
the expression of CR3 on the neutrophil surface and the total expression and
activity of signaling proteins from the Syk-GTPase pathway, which is involved in
actin polymerization. CTX down-regulated both subunits of CR3, as well as, the
activity of Syk, Vav1, Cdc42, Rac1 and RhoA, and the expression of the subunit 1B
from Arp2/3. Together, our findings demonstrated that CTX inhibits the
functionally of bone marrow neutrophils and that this effect may be associated
with an impairment of the Syk-GTPase pathway. This study demonstrates, for the
first time, that the sustained down-modulatory effect of CTX on circulating and
peritoneal neutrophils is associated with functional modifications of neutrophils
still in the bone marrow, and it also contributes to a better understanding of
the anti-inflammatory effect of CTX.
PMID- 28688805
TI - Low level of ochratoxin A affects genome-wide expression in kidney of pig.
AB - Ochratoxin A (OTA) is a mycotoxin produced by fungus belonging to Aspergillus and
Penicillium genra. The aim of the present paper was to investigate if a low
concentration OTA has toxic effect in pigs. Twelve piglets were fed with a
control or an OTA (0.05 mg/kg feed) contaminated diet. After 30 days, animals
were slaughtered and samples of blood and kidney were used for further analyses.
The mycotoxin analyses showed a significant higher (6.25 times) concentration of
OTA in the kidney of OTA intoxicated piglets than in control ones. While OTA has
no effect on the urea and creatinine concentration, the microarray analysis of
the effect of OTA on genome wide expression in the kidney of intoxicated piglets,
revealed that approximately 105 different transcripts were significantly altered.
As shown by the microarray results, 0.05 mg/kg of OTA can principally interfere
with: i) canonical pathways (CD28 Signaling in T Helper Cells, Role of NFAT in
Regulation of the Immune Response, Relaxin Signaling, IL-1 Signaling) ii)
molecular and cellular function (cellular movement cellular function and
maintenance, cellular growth and proliferation cellular assembly and
organization, cell death and survival) etc. However, alteration of renal and
urological system development and function and renal necrosis predicted through
Ingenuity Pathway Analysis (IPA) were not supported by clinical pathological
data. In conclusion, OTA toxicity was found even at low concentration of toxin,
correlated with the activation of immune response pathways, oxidative stress
response and early carcinogenic events. This effect need to be further
investigated and analyzed in the context of human health.
PMID- 28688806
TI - Evaluation of the genotoxicity of alpha-amanitin in mice bone marrow cells.
AB - Alpha-amanitin is a known cytotoxic substance found in some mushroom species
including Amanita phalloides. Its main mechanism of action is to block the
transcription, which can lead to cell death. Lack of reports on the genotoxicity
of this toxin was an inspiration for undertaking this experiment. Genotoxic
effect of alpha-amanitin on balb/c mice bone marrow cells was tested using: comet
assay and chromosomal aberration test. The tested substance was given once by
intraperitoneal administration to animals at doses: 0.1 mg/kg, 0.15 mg/kg and
0.25 mg/kg (LD50) body weight with 48 h exposure. The comet assay demonstrated a
statistically significant increase in DNA damage for all the investigated alpha
amanitin doses compared to the negative control (p < 0.0001). The exposure to
0.15 and 0.25 mg/kg doses of alpha-amanitin also generated a statistically
significant increase in the frequency of chromosomal aberrations in bone marrow
cells of mice compared to the negative control (p < 0.05). The genotoxic effect
induced by alpha-amanitin in mammalian cells can result in genome instability and
its functional consequences.
PMID- 28688807
TI - Modulation of hepatic glutathione transferases isoenzymes in three bivalve
species exposed to purified microcystin-LR and Microcystis extracts.
AB - This study compares the role of hepatic cytosolic glutathione transferases (cGST)
isoforms of three different bivalve species to a Microcystis aeruginosa extract
and purified MC-LR exposure (both at 150 MUg MC-LR L-1) for 24 h.
Characterization and alterations of the cytosolic GST activities in Mytilus
galloprovincialis, Ruditapes philippinarum and Corbicula fluminea were measured
using four class-specific substrates and changes in individual GST isoforms
expression were achieved by a subsequent two-dimensional electrophoresis
analysis. Evaluation of cGST activity basal levels using the four class-specific
substrates denoted quantitative differences between the three bivalves. Purified
MC-LR did not induce any significant response from bivalves. On the other hand,
cell extracts caused significant alterations according to bivalves and
substrates. Among the three bivalves, only R. philippinarum showed a significant
induction of cGST activity using generic 1-chloro-2,4-dinitrobenzene (CDNB)
substrate. However, no significant alterations were detected in these clams by
cell extracts using the other specific substrates. In contrast, C. fluminea
revealed significant induction of cGST activity when using 3,4
dichloronitrobenzene (DCNB) and ethacrynic acid (EA). In M. galloprovincialis,
cell extracts promoted a significant decrease of cGST activity when using EA
substrate. Altered protein expression was quantitatively detected upon exposure
to cell extracts for one spot in R. philippinarum and another for C. fluminea,
both upregulated (2.0 and 8.5-fold, respectively) and identified as a sigma1
class GST in the case of the first. The results showed that the three bivalves
presented specific adaptive biotransformation responses to MCs and other
cyanobacteria compounds supported by the modulation of distinct cGST classes.
PMID- 28688808
TI - Conjunctival granuloma post pulley fixation suture.
AB - Pulley fixation sutures to the medial rectus muscles have been used to manage
variable-angle esotropia and convergence excess esotropia. Most techniques use a
nonabsorbable suture. The posterior location of the sutures usually minimizes
complications. We report a case of chronic conjunctival granuloma occurring after
pulley fixation suture to the medial rectus muscle.
PMID- 28688809
TI - Use of the Spot Vision Screener for patients with developmental disability.
AB - PURPOSE: To determine whether the Spot Vision Screener effectively detects
amblyopia risk factors (ARFs) in patients with developmental disability using the
2013 guidelines of the American Association for Pediatric Ophthalmology and
Strabismus (AAPOS). METHODS: Children with developmental disability presenting
for complete pediatric ophthalmologic examination were prospectively enrolled
between June 2012 and March 2016. The following data were analyzed: presence of
ARFs according to the AAPOS guidelines, refraction, eye alignment, and other
ocular pathology. RESULTS: A total of 100 children (average age, 5.7 years;
range, 2.2- 9.2 years) were included. The prevalence of ARFs in this cohort was
38%. The sensitivity of the Spot Vision Screener in detecting amblyopia risk
factors was 84%; the specificity, 62%. The positive predictive value was 58%; the
negative predictive value, 86%. CONCLUSIONS: In our study cohort the Spot Vision
Screener provided good sensitivity and adequate specificity for a screening
examination. Automated screeners may be useful in screening children with
developmental disability.
PMID- 28688810
TI - The risk assessment of pathological fracture in the proximal femur using a CT
based finite element method.
AB - BACKGROUND: Patients who have lytic bone lesions in their proximal femurs are at
risk for pathological fracture. Lesions with high fracture risk are surgically
treated using prophylactic osteosynthesis, whereas low-risk lesions are treated
conservatively. However, it is difficult to discriminate between high- and low
risk lesions based on clinical and radiographic findings. The computed tomography
(CT)-based finite element (FE) models are useful for predicting the fracture load
on proximal femoral lytic lesions. MATERIALS AND METHODS: FE models were
constructed from the quantitative CT scans of the femurs using software that
created individual bone shapes and density distributions. Three independent
observers measured the lesion size, Mirels' score, and thickness of the proximal
femur along the horizontal plane. The predictive risk values of the proximal
femur measured using the CT-based FE analysis were statistically compared.
RESULTS: The patients were divided into two groups (high and low risk). The mean
fracture load was significantly higher in the high-risk group than in the low
risk group (5395 +/- 525 N, 2622 +/- 364 N, respectively, p = 0.0003). No
significant differences in age, body weight, lesion size or Mirels' score were
observed between groups. However, the thickness of the medial cortex in the high
risk group according to the FE analysis was significantly thinner than that in
the low-risk group. Furthermore, the medial cortex thickness was positively
correlated with the predicted fracture load. An optimal cut-off value of 3.67 mm
for the thickness of the inner cortex resulted in 100% sensitivity and 75.1%
specificity values for classifying the patients based on their fracture risk.
CONCLUSIONS: Our findings indicate that the FE method is useful for the
prediction of the pathological fracture. This method shows a versatile potential
for the prediction of pathological fracture and might aid in judging the optimal
treatment to prevent fracture.
PMID- 28688811
TI - Angular deformity correction by guided growth in growing children: Eight-plate
versus 3.5-mm reconstruction plate.
AB - BACKGROUND: Guided growth using the eight-plate (8-plate) is the most commonly
used method to correct angular deformities in children; however, implant failure
has been reported. Recently, the 3.5-mm reconstruction plate (R-plate) has been
used as an alternative option for guided growth; however, hardware prominence has
been problematic. This study aimed to compare the coronal angular deformity
correction results of guided growth between relatively thin 8-plates with
cannulated screws and thick R-plates with solid screws. METHODS: Thirty-nine
physes (24 distal femoral, 15 proximal tibial) in 20 patients underwent
hemiepiphysiodesis using 8-plates, and 61 physes (40 distal femoral, 21 proximal
tibial) in 35 patients underwent hemiepiphysiodesis using R-plates. Coronal
angular corrections were measured and compared preoperatively, and after the
completion of corrections. Amounts and rates of correction and complications were
compared between the groups. RESULTS: Mean body mass index was 18.7 kg/m2 in the
8-plate group, and 22.7 kg/m2 in the R-plate group. Angular correction was
achieved in all deformities at a mean of 13.7 months and 19.7 months in the 8
plate and the R-plate group, respectively. The mean corrected mechanical lateral
distal femoral angle was 9.0 degrees in the 8-plate group, and 9.9 degrees in
the R-plate group (P = 0.55). The mean corrected medial proximal tibial angle was
7.1 degrees in the 8-plate group, and 9.0 degrees in the R-plate group (P =
0.07). The mean rates of angular correction were also not significantly different
in the distal femur (1.03 degrees /month vs. 0.77 degrees /month, P = 0.2) and
the proximal tibia (0.66 degrees /month vs. 0.63 degrees /month, P = 0.77). There
was one superficial infection in each group, and one case of implant failure in
the R-plate group. Two rebound deformities were observed and needed repeat
hemiepiphysiodesis. Permanent physeal arrest was not observed in this series.
PMID- 28688812
TI - Lipoma arborescens of the hip: A case report.
PMID- 28688813
TI - Reply.
PMID- 28688814
TI - Proceedings: Beyond Ultrasound First Forum on improving the quality of ultrasound
imaging in obstetrics and gynecology.
AB - The Beyond Ultrasound First Forum was conceived to increase awareness that the
quality of obstetric and gynecologic ultrasound can be improved, and is
inconsistent throughout the country, likely due to multiple factors, including
the lack of a standardized curriculum and competency assessment in ultrasound
teaching. The forum brought together representatives from many professional
associations; the imaging community including radiology, obstetrics and
gynecology, and emergency medicine among others; in addition to government
agencies, insurers, industry, and others with common interest in obstetric and
gynecologic ultrasound. This group worked together in focus sessions aimed at
developing solutions on how to standardize and improve ultrasound training at the
resident level and beyond. A new curriculum and competency assessment program for
teaching residents (obstetrics and gynecology, radiology, and any other specialty
doing obstetrics and gynecology ultrasound) was presented, and performance
measures of ultrasound quality in clinical practice were discussed. The aim of
this forum was to increase and unify the quality of ultrasound examinations in
obstetrics and gynecology with the ultimate goal of improving patient safety and
quality of clinical care. This report describes the proceedings of this
conference including possible approaches to resident teaching and means to
improve the inconsistent quality of ultrasound examinations performed today.
PMID- 28688815
TI - Albumin-Bilirubin and Platelet-Albumin-Bilirubin Grades Accurately Predict
Overall Survival in High-Risk Patients Undergoing Conventional Transarterial
Chemoembolization for Hepatocellular Carcinoma.
AB - PURPOSE: To evaluate albumin-bilirubin (ALBI) and platelet-albumin-bilirubin
(PALBI) grades in predicting overall survival in high-risk patients undergoing
conventional transarterial chemoembolization for hepatocellular carcinoma (HCC).
MATERIALS AND METHODS: This single-center retrospective study included 180 high
risk patients (142 men, 59 y +/- 9) between April 2007 and January 2015. Patients
were considered high-risk based on laboratory abnormalities before the procedure
(bilirubin > 2.0 mg/dL, albumin < 3.5 mg/dL, platelet count < 60,000/mL,
creatinine > 1.2 mg/dL); presence of ascites, encephalopathy, portal vein
thrombus, or transjugular intrahepatic portosystemic shunt; or Model for End
Stage Liver Disease score > 15. Serum albumin, bilirubin, and platelet values
were used to determine ALBI and PALBI grades. Overall survival was stratified by
ALBI and PALBI grades with substratification by Child-Pugh class (CPC) and
Barcelona Liver Clinic Cancer (BCLC) stage using Kaplan-Meier analysis. C-index
was used to determine discriminatory ability and survival prediction accuracy.
RESULTS: Median survival for 79 ALBI grade 2 patients and 101 ALBI grade 3
patients was 20.3 and 10.7 months, respectively (P < .0001). Median survival for
30 PALBI grade 2 and 144 PALBI grade 3 patients was 20.3 and 12.9 months,
respectively (P = .0667). Substratification yielded distinct ALBI grade survival
curves for CPC B (P = .0022, C-index 0.892), BCLC A (P = .0308, C-index 0.887),
and BCLC C (P = .0287, C-index 0.839). PALBI grade demonstrated distinct survival
curves for BCLC A (P = 0.0229, C-index 0.869). CPC yielded distinct survival
curves for the entire cohort (P = .0019) but not when substratified by BCLC stage
(all P > .05). CONCLUSIONS: ALBI and PALBI grades are accurate survival metrics
in high-risk patients undergoing conventional transarterial chemoembolization for
HCC. Use of these scores allows for more refined survival stratification within
CPC and BCLC stage.
PMID- 28688816
TI - Combined Therapy of Transcatheter Arterial Chemoembolization and Radiofrequency
Ablation versus Surgical Resection for Single 2-3 cm Hepatocellular Carcinoma: A
Propensity-Score Matching Analysis.
AB - PURPOSE: To compare therapeutic outcomes of radiofrequency (RF) ablation combined
with transcatheter arterial chemoembolization vs surgical resection (SR) for
single 2-3 cm hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Seventy
patients underwent combined chemoembolization/RF ablation therapy and 84
underwent SR. Local tumor progression (LTP), intrahepatic distant recurrence
(IDR), disease-free survival (DFS), and overall survival (OS) rates, as well as
major complications and duration of hospital stay, were compared between groups
before and after propensity-score matching. RESULTS: LTP and IDR had developed in
9 (12.9%) and 24 (34.3%) patients in the combined treatment group and in 7 (8.3%)
and 24 (28.6%) patients in the SR group (P = .262 and P = .252, respectively).
The 1-, 3-, 4-, and 5-year DFS rates were similar between groups (82.6%, 53.2%,
53.2%, and 37.6%, respectively, vs 84.5%, 63.6%, 59.2%, and 52.1%, respectively;
P = .278), and 1-, 3-, 4-, and 5-year OS rates were also comparable (94.2%,
81.2%, 74.1%, and 59.4%, respectively, vs 95.2%, 86.3%, 84.0%, and 80.3%,
respectively; P = .081). After matching (n = 98), LTP, IDR, DFS, and OS rates
were still similar (P = .725, P = .826, P = .484, and P = .578, respectively).
Major complication rate was not significantly different (2.9% vs. 6.0%; P =
.596); however, after matching, major complication rate was higher in SR group
(2.0% vs. 6.1%; P < .001). Hospital stays were significantly longer in the SR
group (16.6 +/- 6.7 d vs 8.5 +/- 4.1 d; P < .001). CONCLUSIONS: Before and after
matching, there were no significant differences in long-term therapeutic outcomes
between combined chemoembolization/RF ablation and SR groups. Therefore, combined
chemoembolization/RF ablation therapy may be an alternative treatment for single
2-3 cm HCCs.
PMID- 28688817
TI - Early restrictive-constrictive physiology in a cardiac allograft recipient.
PMID- 28688819
TI - Diabetes in sub-Saharan Africa: let us not forget type 1.
PMID- 28688820
TI - The crisis of diabetes in sub-Saharan Africa.
PMID- 28688818
TI - Diabetes in sub-Saharan Africa: from clinical care to health policy.
PMID- 28688821
TI - Does an Association Exist Between the Presence of Lower Third Molar and
Mandibular Angle Fractures?: A Meta-Analysis.
AB - PURPOSE: The current data suggest that the presence of lower third molars
predisposes the patient to a greater risk of mandibular angle fracture. Thus, the
present review sought to determine whether an association exists between the
presence of a lower third molar and the occurrence of a mandibular angle fracture
in adults and to assess the influence of third molar position according to the
Pell and Gregory classification. MATERIALS AND METHODS: The present study was a
systematic review and meta-analysis of analytical observational studies. The
present review included all reports of the relationship between mandibular angle
fractures and lower third molars. No restriction regarding year, language, or
publication status was used. The review protocol was registered at the PROSPERO
database (registration no. CRD42016047057). Electronic searches unrestricted for
publication period and language were performed in the PubMed, Scopus, SciELO, and
Latin American and Caribbean Health Sciences databases. Google Scholar and
OpenGrey databases were used to search the "gray literature," avoiding selection
and publication biases. The entire search was performed by 2 eligibility
reviewers. Association and proportion meta-analyses were planned for the studies
with sufficient data. The primary predictor variable was the relationship between
the presence of a lower third molar and the development of mandibular angle
fractures. The secondary outcome variables were the vertical and horizontal
positions of the lower third molar, according to the Pell and Gregory
classification and their relationship to the susceptibility to developing a
mandibular angle fracture. RESULTS: The search strategies resulted in 411
studies, from which 16 were selected for qualitative and quantitative review. The
association meta-analysis included all the selected studies and showed that
patients with lower third molars are 3.16 times more likely to develop mandibular
angle fractures. The proportion meta-analysis included 5 studies and showed that
the overall rate of mandibular angle fractures was 51.58% and that positions III
and C are more likely to result in fracture, with a rate of 59.84 and 63.67%,
respectively. CONCLUSIONS: The results of the present study have shown that the
presence of impacted third molars increases by 3.16 times the risk of mandibular
angle fractures in adults, with the greatest risk present when third molars are
classified as IIIC according to Pell and Gregory. The available evidence is not
sufficiently robust to determine whether third molar presence or the level of
impaction is the main causative factor for the occurrence of mandibular angle
fractures.
PMID- 28688822
TI - Visual food cues decrease postprandial glucose concentrations in lean and obese
men without affecting food intake and related endocrine parameters.
AB - The abundance of highly palatable food items in our environment represents a
possible cause of overconsumption. Neuroimaging studies in humans have
demonstrated that watching pictures of food increases activation in brain areas
involved in homeostatic and hedonic food cue processing. Nevertheless, the impact
of food cues on actual food intake and metabolic parameters has not been
systematically investigated. We tested the hypothesis that watching high-calorie
food cues increases food intake and modifies anticipatory blood parameters in
lean and especially in obese men. In 20 normal-weight and 20 obese healthy fasted
men, we assessed the effects of watching pictures of high-calorie food items
versus neutral contents on food intake measured during a standardized test buffet
and subsequent snacking as well as on glucose homeostasis and endocrine
parameters. Compared to neutral pictures, viewing food pictures reduced
postprandial blood glucose concentrations in lean (p = 0.016) and obese (p =
0.044) subjects, without any differences in insulin or C-peptide concentrations
(all p > 0.4). Viewing food pictures did not affect total calorie intake during
the buffet (all p > 0.5) and snack consumption (all p > 0.4). Concentrations of
ghrelin, adrenocorticotropic hormone (ACTH), cortisol, and glucagon also remained
unaffected (all p > 0.08). These data indicate that preprandial processing of
food cues curbs postprandial blood glucose excursions, without immediately
affecting eating behavior in normal-weight and obese men. Findings indicate that
exposure to food cues does not acutely trigger calorie overconsumption but rather
improves the glucoregulatory response to food intake.
PMID- 28688823
TI - PAK6-Associated Support Vector Machine Classifier: A New Way to Evaluate Response
and Survival of Gastric Cancer Treated by 5-FU/Oxaliplatin Chemotherapy.
PMID- 28688824
TI - White Matter Lesions are Associated with Specific Depressive Symptom Trajectories
among Incident Depression and Dementia Populations: Three-City Dijon MRI Study.
AB - OBJECTIVE: Evidence is mixed as to whether periventricular or deep white matter
hyperintensities (WMHs) increase the risk for depressive symptoms, partly because
of heterogeneity in depression measurement, short follow-up, and confounding by
prodromal dementia. The study objective was to evaluate WMH volume in relation to
discrete depressive symptoms over 10 years, stratifying by incident depression
and dementia. METHODS: In this prospective longitudinal cohort study of a
representative population sample from Dijon, France, 1,440 participants aged 65
80 years (median age: 72 years; 59.5% women) without depression, dementia, or
stroke at baseline were studied. Baseline T2-weighted images were obtained in a
1.5-T scanner to quantify WMHs (log cm3). Clinic visits were performed up to five
times in a 10-year period to assess incident neurologic diseases and
comorbidities. Depressive symptoms were measured with the Center for
Epidemiologic Studies Depression Scale and converted to factor z scores,
representing somatic symptoms, depressed affect, low positive affect, and
interpersonal problems. RESULTS: Periventricular WMH volume was uniquely
associated with low positive affect among incident depression cases (beta = 0.15;
95% confidence interval [CI]: 0.02-0.29; p = 0.026). Deep WMH volume was uniquely
associated with depressed affect among incident dementia cases (beta = 0.36; 95%
CI: 0.05-0.68; p = 0.025). WMH volume (periventricular, deep, and total) was
associated with interpersonal problems among persons who developed dementia with
depression. CONCLUSION: The findings highlight that regional WMH volumes and
specific depressive symptoms have clinical and prognostic relevance to help
differentiate between persons at risk for depression and dementia.
PMID- 28688825
TI - Three-Dimensional Bio-Printed Scaffold Sleeves With Mesenchymal Stem Cells for
Enhancement of Tendon-to-Bone Healing in Anterior Cruciate Ligament
Reconstruction Using Soft-Tissue Tendon Graft.
AB - PURPOSE: To investigate the efficacy of the insertion of 3-dimensional (3D) bio
printed scaffold sleeves seeded with mesenchymal stem cells (MSCs) to enhance
osteointegration between the tendon and tunnel bone in anterior cruciate ligament
(ACL) reconstruction in a rabbit model. METHODS: Scaffold sleeves were fabricated
by 3D bio-printing. Before ACL reconstruction, MSCs were seeded into the scaffold
sleeves. ACL reconstruction with hamstring tendon was performed on both legs of
15 adult rabbits (aged 12 weeks). We implanted 15 bone tunnels with scaffold
sleeves with MSCs and implanted another 15 bone tunnels with scaffold sleeves
without MSCs before passing the graft. The specimens were harvested at 4, 8, and
12 weeks. H&E staining, immunohistochemical staining of type II collagen, and
micro-computed tomography of the tunnel cross-sectional area were evaluated.
Histologic assessment was conducted with a histologic scoring system. RESULTS: In
the histologic assessment, a smooth bone-to-tendon transition through broad
fibrocartilage formation was identified in the treatment group, and the interface
zone showed abundant type II collagen production on immunohistochemical staining.
Bone-tendon healing histologic scores were significantly higher in the treatment
group than in the control group at all time points. Micro-computed tomography at
12 weeks showed smaller tibial (control, 9.4 +/- 0.9 mm2; treatment, 5.8 +/- 2.9
mm2; P = .044) and femoral (control, 9.6 +/- 2.9 mm2; treatment, 6.0 +/- 1.0 mm2;
P = .03) bone-tunnel areas in the treated group than in the control group.
CONCLUSIONS: The 3D bio-printed scaffold sleeve with MSCs exhibited excellent
results in osteointegration enhancement between the tendon and tunnel bone in ACL
reconstruction in a rabbit model. CLINICAL RELEVANCE: If secure biological
healing between the tendon graft and tunnel bone can be induced in the early
postoperative period, earlier, more successful rehabilitation may be facilitated.
Three-dimensional bio-printed scaffold sleeves with MSCs have the potential to
accelerate bone-tendon healing in ACL reconstruction.
PMID- 28688826
TI - Biomechanical Analysis of Latarjet Screw Fixation: Comparison of Screw Types and
Fixation Methods.
AB - PURPOSE: To compare the initial fixation stability, failure strength, and mode of
failure of 5 different screw types and fixation methods commonly used for the
classic Latarjet procedure. METHODS: Thirty-five fresh-frozen cadaveric shoulder
specimens were allocated into 5 groups. A 25% anteroinferior glenoid defect was
created, and a classic Latarjet coracoid transfer procedure was performed. All
grafts were fixed with 2 screws, differing by screw type and/or fixation method.
The groups included partially threaded solid 4.0-mm cancellous screws with
bicortical fixation, partially threaded solid 4.0-mm cancellous screws with
unicortical fixation, fully threaded solid 3.5-mm cortical screws with bicortical
fixation, partially threaded cannulated 4.0-mm cancellous screws with bicortical
fixation, and partially threaded cannulated 4.0-mm captured screws with
bicortical fixation. All screws were stainless steel. Outcomes included cyclic
creep and secant stiffness during cyclic loading, as well as load and work to
failure during the failure test. Intergroup comparisons were made by a 1-way
analysis of variance. RESULTS: There were no significant differences among
different screw types or fixation methods in cyclic creep or secant stiffness
after cyclic loading or in load to failure or work to failure during the failure
test. Post-failure radiographs showed evidence of screw bending in only 1
specimen that underwent the Latarjet procedure with partially threaded solid
cancellous screws with bicortical fixation. The mode of failure for all specimens
analyzed was screw cutout. CONCLUSIONS: In this biomechanical study, screw type
and fixation method did not significantly influence biomechanical performance in
a classic Latarjet procedure. When performing this procedure, surgeons may
continue to select the screw type and method of fixation (unicortical or
bicortical) based on preference; however, further studies are required to
determine the optimal method of treatment. CLINICAL RELEVANCE: Surgeons may
choose the screw type and fixation method based on preference when performing the
Latarjet procedure.
PMID- 28688827
TI - Arthroscopic Versus Open Rotator Cuff Repair: Which Has a Better Complication and
30-Day Readmission Profile?
AB - PURPOSE: To provide a comparative 30-day postoperative analysis of complications
and unplanned readmission rates, using the National Surgical Quality Improvement
Program database, after open or arthroscopic rotator cuff repair (RCR). METHODS:
The American College of Surgeons National Surgical Quality Improvement Program
database was reviewed for postoperative complications after open or arthroscopic
RCR over an 8-year period, from 2007 through 2014. Patients were identified by
use of Current Procedural Terminology codes. The open group contained 3,590 cases
(21.8%) and the arthroscopic group had 12,882 cases (78.2%), for a total of
16,472 patients undergoing RCR. The risk of complications was compared between
the 2 groups, along with patient demographic characteristics, operative time,
length of stay, and unplanned readmission within 30 days. We compared dichotomous
variables using the Fisher exact test and continuous variables with 1-way
analysis of variance. Relative risks (RRs) and 95% confidence intervals (CIs)
were calculated when appropriate. RESULTS: The open RCR group had a higher
prevalence of patients aged 65 years or older and comorbidities such as
hypertension, diabetes, chronic obstructive pulmonary disease, smoking, and
alcoholism (P < .05). Patients undergoing open RCR had a higher risk of any
adverse event when compared with arthroscopic RCR patients (1.48% vs 0.84%; RR,
1.17; 95% CI, 1.05-1.30; P = .0010). They were also at higher risk of return to
the operating room within 30 days (0.70% vs 0.26%; RR, 1.36; 95% CI, 1.09-1.69; P
= .0004). Open RCR was associated with a longer average hospital stay (0.48 +/-
2.7 days vs 0.23 +/- 4.2 days, P = .0007), whereas arthroscopic RCR had a longer
average operative time (90 +/- 45 minutes vs 79 +/- 45 minutes, P < .0001).
CONCLUSIONS: Although both open and arthroscopic approaches to RCR had low
morbidity, arthroscopy was associated with lower risks of any adverse event and
return to the operating room during the initial 30-day postoperative period.
LEVEL OF EVIDENCE: Level III, retrospective comparative study.
PMID- 28688828
TI - Epidemiology, clinical features, and microbiology of patients with diarrhea in
community clinics in Taiwan.
AB - OBJECTIVE: To investigate the clinical features and microbiology of patients with
diarrheal diseases in Taiwan. METHODS: From March 2014 to October 2014, patients
with diarrheal diseases referred from the community clinics were enrolled into
our prospective study. Demographics and clinical features of the participants
were acquired. Stool samples were examined by the Luminex Gastrointestinal
Pathogen Panel assay. Data were analyzed by SAS version 9.4. RESULTS: A total of
545 patients were enrolled into this study. Male and adults accounted for 52.3%
and 82.6% of patients, respectively. The median age was 36 years.
Enteropathogen(s) was identified in 43.3% of patients and 8.5% of them had more
than one agent in their stool samples. Viruses, especially norovirus GI/GII, were
the predominant agents of gastroenteritis. Moreover, Campylobacter species was
the most common bacterial agent. Bloody stool was frequently reported in patients
with bacterial diarrhea (P = 0.002); contrarily, watery stool was significantly
associated with viral diarrhea (P < 0.0001). Regional variation and seasonality
of microbiological distribution were also observed. CONCLUSION: In Taiwan,
viruses were the predominant pathogens among patients with diarrheal diseases who
visited community clinics. The therapeutic strategies for diarrheal patients
should be based on the epidemiological and clinical characteristics.
PMID- 28688829
TI - Risk factors for hospital acquisition of trimethoprim-sulfamethoxazole resistant
Stenotrophomonas maltophilia in adults: A matched case-control study.
AB - BACKGROUND/PURPOSE: The emergence of trimethoprim-sulfamethoxazole resistant
Stenotrophomonas maltophilia (TSRSM) represents a serious threat to patients. The
aim of current study was to identify risk factors associated with hospital
acquired TSRSM occurrence in adult inpatients. METHODS: We conducted a matched
case-control study in Tri-Service General Hospital, Taipei, Taiwan. From January
2014 through June 2015, case patients with TSRSM and control patients with
trimethoprim-sulfamethoxazole susceptible S. maltophilia (TSSSM) during
hospitalization were identified. Control patients were matched with TSRSM cases
for age (within five years), sex, and site of isolation at a ratio of 1:1.
RESULTS: A total of 266 patients were included in our study (133 cases and 133
matched controls). Bivariable analysis showed that previous exposure to
fluoroquinolone [odds ratio (OR), 2.693; 95% confidence interval (CI, 1.492
5.884; p = 0.002)], length of intensive care unit stay (OR, 1.015 per day; 95%
CI, 1.001-1.030; p = 0.041), and length of hospital stay (OR, 1.012 per day; 95%
CI, 1.002-1.023; p = 0.018) prior to S. maltophilia isolation were associated
with TSRSM occurrence. A multivariable analysis showed that previous exposure to
fluoroquinolone (OR, 3.158; 95% CI, 1.551-6.430; p = 0.002) was an independent
risk factor for TSRSM occurrence after adjustment. CONCLUSION: Previous
fluoroquinolone use was an independent risk factor for hospital-acquired TSRSM
occurrence in adult inpatients, suggesting that judicious administration of
fluoroquinolone may be important for limiting TSRSM occurrence.
PMID- 28688830
TI - Differential effects of renal denervation on arterial baroreceptor function in
Goldblatt hypertension model.
AB - Sympathetic vasomotor activity is significantly increased in renovascular
hypertension. Renal denervation (DnX) has emerged as a novel therapy for
resistant hypertension to drug therapy. However, the underlying mechanisms
regarding the reduction in blood pressure (BP) after DnX remain unclear. Thus,
the aim of this study was to evaluate the effects of DnX of a clipped kidney on
the baseline and baroreceptor reflex control of post-ganglionic sympathetic
activity to the contralateral kidney (rSNA) and lumbar (lSNA) nerves in Goldblatt
hypertensive rats (2K1C). Renal denervation of an ischaemic kidney (DxX - all
visible bundles of nerves were dissected - 10% phenol) was performed 5weeks after
clipping (gap width: 0.2mm). Ten days after DnX, BP was significantly reduced
(16%) in the 2K1C compared with the undenervated 2K1C (p<0.05). DnX significantly
reduced basal rSNA (control group (CT): 110+/-8, n=14; 2K1C: 150+/-8, n=12; 2K1C
DnX: 89+/-7, spikes per second (spikes/s); p<0.05, n=8) and lSNA (CT: 137+/-8,
n=8; 2K1C: 202+/-7, n=11; 2K1C DnX: 131+/-7, spikes/s; p<0.05, n=8) only in 2K1C
rats. DnX significantly improved the arterial baroreceptor sensitivity of rSNA
(CT: -2.3+/-0.2, n=11; 2K1C: -0.7+/-0.1, n=8; 2K1C DnX: -1.5+/-0.2,
spikes/s/mmHg; p<0.05, n=5) and heart rate for tachycardic response (CT: -3.9+/
0.5, n=7; 2K1C: -1.9+/-0.1, n=8; 2K1C DnX: -3.3+/-0.4, bpm/mmHg; p<0.05, n=8),
but not for lSNA in 2K1C rats. The results show that DnX normalized baseline
sympathetic vasomotor activity to the lumbar and renal nerves, followed by a
differential improvement in the arterial baroreceptor sensitivity. Whether the
baroreceptor function sensitivity improvement induced by DnX is a cause or a
consequence of BP reduction remains to be determined.
PMID- 28688831
TI - Local chemical sympathectomy of rat bone marrow and its effect on marrow cell
composition.
AB - Existing experimental studies of the effect of sympathetic nerve fibers on bone
marrow cells are based on the systemic administration of neurotoxic 6
hydroxydopamine. The method of global chemical sympathectomy has some serious
disadvantages and could lead to questionable results. We describe a new method of
local chemical sympathectomy of rat femoral bone marrow using guanethidine
(Ismelin) delivery using an osmotic mini pump. Local guanethidine treatment for
14days led to complete elimination of sympathetic fibers in femoral bone marrow
in contrast to bone marrow of contralateral or naive femurs. Ablation of
sympathetic fibers was associated with a loss of rat endothelial cell marker
(RECA) indicating immunophenotype changes in blood vessel endothelial cells, but
no significant effect of guanethidine was found on the survival of endothelial
cells and mesenchymal stem cells in vitro. Moreover, local guanethidine treatment
also elicited a significant reduction of Nestin+/SDF1+ mesenchymal stem cells and
c-Kit+/CD90+ hematopoietic stem cells in femoral bone marrow. Tissue-specific
chemical sympathectomy of rat bone marrow by guanethidine overcomes some of the
drawbacks of systemic administration of neurotoxic compounds like 6
hydroxydopamine and delivers unequivocal evidence on the effects of sympathetic
innervation on the cell content of bone marrow.
PMID- 28688832
TI - Prosthetic Valve Infective Endocarditis With Mycobacterium Fortuitum: Antibiotics
Alone Can Be Curative.
AB - Rapidly growing non-tuberculous mycobacteria (RGM) are a rare, often fatal cause
of infective endocarditis. Although surgery has been the cornerstone of RGM
endocarditis therapy, we present the first documented adult case of Mycobacterium
fortuitum endocarditis cured with antibiotic therapy.
PMID- 28688833
TI - Balloon Aortic Valvuloplasty in the Transcatheter Valve Era: Single Centre
Indications and Early Safety Data in a High Risk Population.
AB - BACKGROUND: The introduction of transcatheter aortic valve implantation (TAVI)
has generated a renewed interest in the techniques available to treat high-risk
patients with severe aortic stenosis (AS). We report our single centre experience
with balloon aortic valvuloplasty (BAV) focussing on indications, procedural
success and 30-day outcomes. METHODS: We retrospectively reviewed all patients
that underwent BAV procedures at our institution between August 2012 and August
2014. Procedural success and complications were adjudicated according to VARC-2
criteria. RESULTS: Fifty-one consecutive adult patients with severe symptomatic
AS underwent a total of 55 BAV procedures. The patients had a mean age of 88+/
5.7 years and all had extensive comorbidities with a high surgical risk (mean
logistic EuroSCORE of 25.22%+/-14.5%). Indications for BAV included palliation of
symptoms n=42 (76%); bridge to definitive valve replacement (n=6, 11%); and
evaluation of response (n=6, 11%). The procedure was completed in all patients
with no intraprocedural deaths (within 24hours) and low 30-day mortality at 3.9%
(n=2). Minor vascular complications occurred in 11.8% (n=6), whilst permanent
pacemaker implantation was required in 5.8% (n=3). There were no cases of
myocardial infarction, stroke, tamponade, severe aortic regurgitation or major
vascular complications during 30-day follow-up. CONCLUSIONS: Balloon aortic
valvuloplasty may be performed safely and effectively with high procedural
success and low 30-day complications, even in a very high-risk and elderly cohort
of patients in whom the role of TAVI is uncertain or inappropriate.
PMID- 28688834
TI - Inter-hemispheric control of vestibular thresholds.
PMID- 28688836
TI - A framework for identifying the adaptations responsible for differences in
pegboard times between middle-aged and older adults.
AB - Time to complete two tests of manual dexterity, the 9-hole Peg Test and Grooved
Pegboard Test, increases with advancing age. However, the adaptations responsible
for the differences in pegboard times between middle-aged and older adults are
largely unknown. Potential mechanisms include neuromuscular characteristics,
cognitive function, and cutaneous sensation. To provide a tractable framework to
address these gaps in knowledge, the purpose of the current study was to identify
the latent variables underlying age-associated differences in time to complete
the 9-hole and grooved pegboard tests. The approach involved an independent
component analysis that identified associations between the two pegboard times
for the two groups of participants with two to six secondary outcomes. The common
association across three of the four conditions (two groups and two pegboard
tests) was features derived from force-matching tasks requiring submaximal
isometric contraction. In addition, there were significant associations for older
adults between age, measures of cognitive function, and pegboard times.
Nonetheless, the significant associations were unique for each age group and
pegboard test. The results provide a framework for subsequent mechanistic studies
to identify the adaptations underlying age-associated declines in manual
dexterity.
PMID- 28688837
TI - Tendon Disorders After Total Hip Arthroplasty: Evaluation and Management.
AB - BACKGROUND: Most patients who undergo total hip arthroplasty are very satisfied
with their outcomes. However, there is a small subset of patients who have
persistent pain after surgery. The etiology of pain after total hip arthroplasty
varies widely; however, tendon disorders are a major cause of debilitating pain
that often go unrecognized. METHODS: We performed a literature review to identify
the most common tendon pathologies after total hip arthroplasty which include
iliopsoas tendinitis, greater trochanteric pain syndrome, snapping hip syndrome,
and abductor tendinopathy. RESULTS: We present a simplified approach highlighting
the presentation and management of patients with suspected tendinopathies after
total hip arthroplasty. These tendinopathies are treatable, and management begins
with nonoperative modalities; however, in cases not responsive to conservative
management, operative intervention may be necessary. CONCLUSION: Tendinopathies
after total hip arthroplasty sometimes go unrecognized but when treated can
result in higher surgeon and patient satisfaction.
PMID- 28688838
TI - James Crichton-Browne.
PMID- 28688839
TI - Training non-physicians as neurosurgeons in sub-Saharan Africa.
PMID- 28688840
TI - Impact of clinical exomes in neurodevelopmental and neurometabolic disorders.
AB - Whole exome sequencing (WES) is well established in research and is now being
introduced into clinically indicated diagnostics (so-called clinical exomes). We
evaluated the diagnostic yield and clinical implications of WES in 72 patients
from 60 families with undiagnosed neurodevelopmental disorders (NDD),
neurometabolic disorders, and dystonias. Pathogenic or likely pathogenic variants
leading to a molecular diagnosis could be identified in 21 of the 60 families
(overall 35%, in 36% of patients with NDD, in 43% of patients with neurometabolic
disorders, in 25% of patients with dystonias). In one family two coexisting
autosomal recessive diseases caused by homozygous pathogenic variants in two
different genes were diagnosed. In another family, a homozygous frameshift
variant in STRADA was found to cause a severe NDD with early onset epilepsy,
brain anomalies, hypotonia, heart defect, nephrocalcinosis, macrocephaly and
distinctive facies so far designated as PMSE (polyhydramnios, megalencephaly,
symptomatic epilepsy) syndrome. In 7 of the 21 families with a molecular
diagnosis the pathogenic variants were only identified by clinical follow-up,
manual reevaluation of the literature, a change of filter setting, and/or
reconsideration of inheritance pattern. Most importantly, clinical implications
included management changes in 8 cases and impact on family planning in 20
families with a molecular diagnosis. This study shows that reevaluation and
follow-up can improve the diagnostic rate and that WES results have important
implications on medical management and family planning. Furthermore, we could
confirm STRADA as a gene associated with syndromic ID but find it questionable if
the current designation as PMSE depicts the most important clinical features.
PMID- 28688841
TI - How MR1 Presents a Pathogen Metabolic Signature to Mucosal-Associated Invariant T
(MAIT) Cells.
AB - Mucosal-associated invariant T (MAIT) cells are innate-like lymphocytes
restricted by the antigen (Ag)-presenting molecule MHC class I (MHC I)-related
protein 1 (MR1). The Ags presented by MR1 are vitamin B-related Ags (VitBAgs),
'building-block' metabolites of riboflavin that are synthesized by a range of
microbes. MR1 presentation is thus a unique mechanism for the immune detection of
a pathogen metabolic signature. While the full picture of how MR1 accomplishes
this remains incomplete, recent data show that, unlike other MHC molecules, MR1
operates by a presentation-on-demand mechanism. In the absence of metabolite
ligands MR1 is mostly stored in the endoplasmic reticulum (ER). Ligand binding
leads to the formation of a Schiff-base bond between MR1 and its ligand,
triggering a 'molecular switch' in MR1 that allows trafficking of the complexes
to the cell surface. The complexes are subsequently internalized and mostly
degraded irrespective of the affinity of the interaction between MR1 and its
ligands. Here we review past and recent studies that have contributed to defining
this pathway and propose new directions for a full understanding of the role and
mechanisms of MR1 Ag presentation.
PMID- 28688842
TI - Computational Modeling of Polymeric Physicochemical Properties for Formulation
Development of a Drug Containing Basic Functionality.
AB - In the present research, predictive models were developed by correlating
polymeric properties with characteristics of a formulation containing a drug with
basic heterocycle (glipizide). Glipizide tablets containing different polymers
from 3 categories (immediate, moderate, and extended release) were prepared and
evaluated. Dissolution kinetics indicated Korsmeyer-Peppas as the best-fit model,
whereas transportability was influenced by release rate and hydrophobicity of the
drug. Calculated polymeric descriptors were correlated with formulation
properties for the development of predictive quantitative structure-property
relationship models. Regression coefficients and subsequent validation of
developed models indicated potential predictability of the model for formulation
properties containing any drug with basic heterocycle. Such models could also
help to decide the formulation composition for desired characteristics with
saving of time and formulation cost.
PMID- 28688843
TI - Chemical Stability of the Botanical Drug Substance Crofelemer: A Model System for
Comparative Characterization of Complex Mixture Drugs.
AB - As the second of a 3-part series of articles in this issue concerning the
development of a mathematical model for comparative characterization of complex
mixture drugs using crofelemer (CF) as a model compound, this work focuses on the
evaluation of the chemical stability profile of CF. CF is a biopolymer containing
a mixture of proanthocyanidin oligomers which are primarily composed of
gallocatechin with a small contribution from catechin. CF extracted from drug
product was subjected to molecular weight-based fractionation and thiolysis.
Temperature stress and metal-catalyzed oxidation were selected for accelerated
and forced degradation studies. Stressed CF samples were size fractionated,
thiolyzed, and analyzed with a combination of negative-ion electrospray
ionization mass spectrometry (ESI-MS) and reversed-phase-HPLC with UV absorption
and fluorescence detection. We further analyzed the chemical stability data sets
for various CF samples generated from reversed-phase-HPLC-UV and ESI-MS using
data-mining and machine learning approaches. In particular, calculations based on
mutual information of over 800,000 data points in the ESI-MS analytical data set
revealed specific CF cleavage and degradation products that were differentially
generated under specific storage/degradation conditions, which were not initially
identified using traditional analysis of the ESI-MS results.
PMID- 28688844
TI - Performance of granular activated carbon to remove micropollutants from municipal
wastewater-A meta-analysis of pilot- and large-scale studies.
AB - For reducing organic micropollutants (MP) in municipal wastewater effluents,
granular activated carbon (GAC) has been tested in various studies. We did
systematic literature research and found 44 studies dealing with the adsorption
of MPs (carbamazepine, diclofenac, sulfamethoxazole) from municipal wastewater on
GAC in pilot- and large-scale plants. Within our meta-analysis we plot the bed
volumes (BV [m3water/m3GAC]) until the breakthrough criterion of MP-BV20% was
reached, dependent on potential relevant parameters (empty bed contact time EBCT,
influent DOC DOC0 and manufacturing method). Moreover, we performed statistical
tests (ANOVAs) to check the results for significance. Single adsorbers operating
time differs i.e. by 2500% until breakthrough of diclofenac-BV20% was reached
(800-20,000 BV). There was still elimination of the "very well/well" adsorbable
MPs such as carbamazepine and diclofenac even when the equilibrium of DOC had
already been reached. No strong statistical significance of EBCT and DOC0 on MP
BV20% could be found due to lack of data and the high heterogeneity of the
studies using GAC of different qualities. In further studies, adsorbers should be
operated ?20,000 BV for exact calculation of breakthrough curves, and the
following parameters should be recorded: selected MPs; DOC0; UVA254; EBCT;
product name, manufacturing method and raw material of GAC; suspended solids
(TSS); backwash interval; backwash program and pressure drop within adsorber.
Based on our investigations we generally recommend using reactivated GAC to
reduce the environmental impact and to carry out tests on pilot scale to collect
reliable data for process design.
PMID- 28688845
TI - Assessing the phytoremediation potential of crop and grass plants for atrazine
spiked soils.
AB - Pollution of soil and groundwater by atrazine has become an increasing
environmental concern in the last decade. A phytoremediation test using plastic
pots was conducted in order to assess the ability of several crops and grasses to
remove atrazine from a soil of low permeability spiked with this herbicide. Four
plant species were assessed for their ability to degrade or accumulate atrazine
from soils: two grasses, i.e., ryegrass (Lolium perenne) and tall fescue (Festuca
arundinacea), and two crops, i.e., barley (Hordeum vulgare) and maize (Zea mays).
Three different doses of atrazine were used for the contamination of the pots: 2,
5 and 10 mg kg-1. 16 days after spiking, the initial amount of atrazine was
reduced by 88.6-99.6% in planted pots, while a decrease of only 63.1-78.2% was
found for the unplanted pots, thus showing the contribution of plants to soil
decontamination. All the plant species were capable of accumulating atrazine and
its N-dealkylated metabolites, i.e., deethylatrazine and deisopropylatrazine, in
their tissues. Some toxic responses, such as biomass decreases and/or chlorosis,
were observed in plants to a greater or lesser extent for initial soil doses of
atrazine above 2 mg kg-1. Maize was the plant species with the highest ability to
accumulate atrazine derivatives, reaching up to 38.4% of the initial atrazine
added to the soil. Rhizosphere degradation/mineralization by microorganisms or
plant enzymes, together with degradation inside the plants, have been proposed as
the mechanisms that contributed to a higher extent than plant accumulation to
explain the removal of atrazine from soils.
PMID- 28688846
TI - Evaluation of nitrate effects in the aqueous photodegradability of selected
phenolic pollutants.
AB - The effect of nitrate in the aqueous photodegradation of five phenolic
environmental pollutants (ortho-phenylphenol, OPP; methyl paraben, MeP; propyl
paraben, PrP; Triclosan, TCS and bisphenol A, BPA) is evaluated. Time-course of
precursor compounds and formation of transformation products (TPs) were
investigated by liquid chromatography quadrupole time-of-flight mass spectrometry
(LC-QTOF-MS). Nitrate showed a positive effect in the removal of selected
pollutants. Observed TPs resulted from hydroxylation, aromatic nitration (with or
without molecule cleavage) and nitro dehalogenation processes. The above
reactions involved the participation of .OH and .NO2 radicals arising from
photolysis of nitrate. Nitro TPs were produced in a different extent depending on
the structure of the precursor pollutant, nitrate concentration, light source
(254 nm UV and solar light) and water matrix (ultrapure, surface and urban
wastewater). Some of these nitro TPs were also observed during UV irradiation of
untreated and unbuffered wastewater, either naturally polluted with parent
phenolic compounds or spiked with these species at the sub MUg L-1 level.
Nitration reactions were particularly favourable for OPP with the generated nitro
TPs displaying a higher stability than the precursor molecule and the
hydroxylated TPs of the same compound.
PMID- 28688847
TI - Pesticide residues in raw and processed maize grains and flour from selected
areas in Dar es Salaam and Ruvuma, Tanzania.
AB - This study investigated the levels of pesticide residues in maize grains and
flour and the effects of processing methods on their levels in maize products in
samples collected in Dar es Salaam and Ruvuma regions. Analysis of cleaned-up
extracts was done using gas chromatography-mass spectrometry (GC-MS). Twelve
pesticides were detected in maize grains and their highest concentrations were up
to 676.1, 11200 and 14 MUg/kg for organochlorines, organophosphorous and
pyrethroid pesticides, respectively. In maize flour, eight pesticides were
detected and the concentrations for organochlorines, organophosphorous and
pyrethroid pesticides were up to 333.3, 2220 and 2 MUg/kg, respectively. Only
dieldrin was detected in cooked samples at a concentration of 2 MUg/kg. The
concentrations of p,p'-DDD, aldrin, dieldrin, chlorpyrifos and pirimiphos methyl
in some grains and flour samples exceeded the maximum residue limit (MRLs). The
findings indicate risks and concerns for public health. Processing methods were
found to cause transformation and reduction of the pesticides.
PMID- 28688848
TI - Electrochemical and/or microbiological treatment of pyrolysis wastewater.
AB - Electrochemical oxidation may be used as treatment to decompose partially or
completely organic pollutants (wastewater) from industrial processes such as
pyrolysis. Pyrolysis is a thermochemical process used to obtain bio-oil from
biomasses, generating a liquid waste rich in organic compounds including
aldehydes and phenols, which can be submitted to biological and electrochemical
treatments in order to minimize its environmental impact. Thus, electrochemical
systems employing dimensionally stable anodes (DSAs) have been proposed to enable
biodegradation processes in subsurface environments. In order to investigate the
organic compound degradation from residual coconut pyrolysis wastewater, ternary
DSAs containing ruthenium, iridium and cerium synthetized by the 'ionic liquid
method' at different calcination temperatures (500, 550, 600 and 700 degrees C)
for the pretreatment of these compounds, were developed in order to allow
posterior degradation by Pseudomonas sp., Bacillus sp. or Acinetobacter sp.
bacteria. The electrode synthesized applying 500 degrees C displayed the highest
voltammetric charge and was used in the pretreatment of pyrolysis effluent prior
to microbial treatment. Regarding biological treatment, the Pseudomonas sp.
exhibited high furfural degradation in wastewater samples electrochemically
pretreated at 2.0 V. On the other hand, the use of Acinetobacter efficiently
degraded phenolic compounds such as phenol, 4-methylphenol, 2,5-methylphenol, 4
ethylphenol and 3,5-methylphenol in both wastewater samples, with and without
electrochemical pretreatment. Overall, the results indicate that the combination
of both processes used in this study is relevant for the treatment of pyrolysis
wastewater.
PMID- 28688849
TI - Clostridium difficile Infection in Contemporary Urologic Practice.
AB - Clostridium difficile infection (CDI) is a high-impact hospital-acquired
condition and a chief driver of excess morbidity, mortality, and treatment cost.
The diagnosis, treatment, and prevention of CDI are key components of any
hospital-based practice. Urologists see a small percentage of all patients with
CDI, but traditionally utilize antibiotic agents that put patients at risk of
CDI. Urologic procedures making use of bowel have a significantly higher rate of
CDI than other procedures. This review addresses concepts that practicing
urologists should be aware of and should be able to put into practice to
diagnose, treat, and prevent CDI.
PMID- 28688850
TI - Crop-associated virus reduces the rooting depth of non-crop perennial native
grass more than non-crop-associated virus with known viral suppressor of RNA
silencing (VSR).
AB - As agricultural acreage expanded and came to dominate landscapes across the
world, viruses gained opportunities to move between crop and wild native plants.
In the Midwestern USA, virus exchange currently occurs between widespread annual
Poaceae crops and remnant native perennial prairie grasses now under
consideration as bioenergy feedstocks. In this region, the common aphid species
Rhopalosiphum padi L. (the bird cherry-oat aphid) transmits several virus species
in the family Luteoviridae, including Barley yellow dwarf virus (BYDV-PAV, genus
Luteovirus) and Cereal yellow dwarf virus (CYDV-RPV and -RPS, genus Polerovirus).
The yellow dwarf virus (YDV) species in these two genera share genetic
similarities in their 3'-ends, but diverge in the 5'-regions. Most notably, CYDVs
encode a P0 viral suppressor of RNA silencing (VSR) absent in BYDV-PAV. Because
BYDV-PAV has been reported more frequently in annual cereals and CYDVs in
perennial non-crop grasses, we examine the hypothesis that the viruses' genetic
differences reflect different affinities for crop and non-crop hosts.
Specifically, we ask (i) whether CYDVs might persist within and affect a native
non-crop grass more strongly than BYDV-PAV, on the grounds that the polerovirus
VSR could better moderate the defenses of a well-defended perennial, and (ii)
whether the opposite pattern of effects might occur in a less defended annual
crop. Because previous work found that the VSR of CYDV-RPS possessed greater
silencing suppressor efficiency than that of CYDV-RPV, we further explored (iii)
whether a novel grass-associated CYDV-RPS isolate would influence a native non
crop grass more strongly than a comparable CYDV-RPV isolate. In growth chamber
studies, we found support for this hypothesis: only grass-associated CYDV-RPS
stunted the shoots and crowns of Panicum virgatum L. (switchgrass), a perennial
native North American prairie grass, whereas crop-associated BYDV-PAV (and
coinfection with BYDV-PAV and CYDV-RPS) most stunted annual Avena sativa L.
(oats). These findings suggest that some of the diversity in grass-infecting
Luteoviridae reflects viral capacity to modulate defenses in different host
types. Intriguingly, while all virus treatments also reduced root production in
both host species, only crop-associated BYDV-PAV (or co-infection) reduced
rooting depths. Such root effects may increase host susceptibility to drought,
and indicate that BYDV-PAV pathogenicity is determined by something other than a
P0 VSR. These findings contribute to growing evidence that pathogenic crop
associated viruses may harm native species as well as crops. Critical next
questions include the extent to which crop-associated selection pressures drive
viral pathogenesis.
PMID- 28688851
TI - Characterization of the dominant inheritance mechanism of Episodic Ataxia type 2.
AB - Episodic Ataxia type 2 (EA2) is an autosomal dominant neuronal disorder linked to
mutations in the Cav2.1 subunit of P/Q-type calcium channels. In vitro studies
have established that EA2 mutations induce loss of channel activity and that EA2
mutants can exert a dominant negative effect, suppressing normal Cav2.1 activity
through protein misfolding and trafficking defects. To date, the role of this
mechanism in the disease pathogenesis is unknown because no animal model exists.
To address this issue, we have generated a mouse bearing the R1497X nonsense
mutation in Cav2.1 (Cav2.1R1497X). Phenotypic analysis of heterozygous
Cav2.1R1497X mice revealed ataxia associated with muscle weakness and generalized
absence epilepsy. Electrophysiological studies of the cerebellar circuits in
heterozygous Cav2.1R1497X mice highlighted severe dysregulations in synaptic
transmission of the two major excitatory inputs as well as alteration of the
spontaneous activity of Purkinje cells. Moreover, these neuronal dysfunctions
were associated with a strong suppression of Cav2.1 channel expression in the
cerebellum of heterozygous Cav2.1R1497X mice. Finally, the presence of Cav2.1 in
cerebellar lipid raft microdomains was strongly impaired in heterozygous
Cav2.1R1497X mice. Altogether, these results reveal a pathogenic mechanism for
EA2 based on a dominant negative activity of mutant channels.
PMID- 28688835
TI - Erratum to "Choices of Stent and Cerebral Protection in the Ongoing ACST-2 Trial:
A Descriptive Study" [Eur J Vasc Endovasc Surg 53 (2017) 617-625].
PMID- 28688852
TI - CDKL5 controls postsynaptic localization of GluN2B-containing NMDA receptors in
the hippocampus and regulates seizure susceptibility.
AB - Mutations in the Cyclin-dependent kinase-like 5 (CDKL5) gene cause severe
neurodevelopmental disorders accompanied by intractable epilepsies, i.e. West
syndrome or atypical Rett syndrome. Here we report generation of the Cdkl5
knockout mouse and show that CDKL5 controls postsynaptic localization of GluN2B
containing N-methyl-d-aspartate (NMDA) receptors in the hippocampus and regulates
seizure susceptibility. Cdkl5 -/Y mice showed normal sensitivity to kainic acid;
however, they displayed significant hyperexcitability to NMDA. In concordance
with this result, electrophysiological analysis in the hippocampal CA1 region
disclosed an increased ratio of NMDA/alpha-amino-3-hydroxy-5-methyl-4
isoxazolepropionic acid (AMPA) receptor-mediated excitatory postsynaptic currents
(EPSCs) and a significantly larger decay time constant of NMDA receptor-mediated
EPSCs (NMDA-EPSCs) as well as a stronger inhibition of the NMDA-EPSCs by the
GluN2B-selective antagonist ifenprodil in Cdkl5 -/Y mice. Subcellular
fractionation of the hippocampus from Cdkl5 -/Y mice revealed a significant
increase of GluN2B and SAP102 in the PSD (postsynaptic density)-1T fraction,
without changes in the S1 (post-nuclear) fraction or mRNA transcripts, indicating
an intracellular distribution shift of these proteins to the PSD. Immunoelectron
microscopic analysis of the hippocampal CA1 region further confirmed postsynaptic
overaccumulation of GluN2B and SAP102 in Cdkl5 -/Y mice. Furthermore, ifenprodil
abrogated the NMDA-induced hyperexcitability in Cdkl5 -/Y mice, suggesting that
upregulation of GluN2B accounts for the enhanced seizure susceptibility. These
data indicate that CDKL5 plays an important role in controlling postsynaptic
localization of the GluN2B-SAP102 complex in the hippocampus and thereby
regulates seizure susceptibility, and that aberrant NMDA receptor-mediated
synaptic transmission underlies the pathological mechanisms of the CDKL5 loss-of
function.
PMID- 28688853
TI - GPR37L1 modulates seizure susceptibility: Evidence from mouse studies and
analyses of a human GPR37L1 variant.
AB - Progressive myoclonus epilepsies (PMEs) are disorders characterized by myoclonic
and generalized seizures with progressive neurological deterioration. While
several genetic causes for PMEs have been identified, the underlying causes
remain unknown for a substantial portion of cases. Here we describe several
affected individuals from a large, consanguineous family presenting with a novel
PME in which symptoms begin in adolescence and result in death by early
adulthood. Whole exome analyses revealed that affected individuals have a
homozygous variant in GPR37L1 (c.1047G>T [Lys349Asn]), an orphan G protein
coupled receptor (GPCR) expressed predominantly in the brain. In vitro studies
demonstrated that the K349N substitution in Gpr37L1 did not grossly alter
receptor expression, surface trafficking or constitutive signaling in transfected
cells. However, in vivo studies revealed that a complete loss of Gpr37L1 function
in mice results in increased seizure susceptibility. Mice lacking the related
receptor Gpr37 also exhibited an increase in seizure susceptibility, while
genetic deletion of both receptors resulted in an even more dramatic increase in
vulnerability to seizures. These findings provide evidence linking GPR37L1 and
GPR37 to seizure etiology and demonstrate an association between a GPR37L1
variant and a novel progressive myoclonus epilepsy.
PMID- 28688854
TI - The time-course of activation in the dorsal and ventral visual streams during
landmark cueing and perceptual discrimination tasks.
AB - Different patterns of high density EEG activity were elicited by the same
peripheral stimuli, in the context of Landmark Cueing and Perceptual
Discrimination tasks. The C1 component of the visual event-related potential
(ERP) at parietal - occipital electrode sites was larger in the Landmark Cueing
task, and source localisation suggested greater activation in the superior
parietal lobule (SPL) in this task, compared to the Perceptual Discrimination
task, indicating stronger early recruitment of the dorsal visual stream. In the
Perceptual Discrimination task, source localisation suggested widespread
activation of the inferior temporal gyrus (ITG) and fusiform gyrus (FFG),
structures associated with the ventral visual stream, during the early phase of
the P1 ERP component. Moreover, during a later epoch (171-270ms after stimulus
onset) increased temporal-occipital negativity, and stronger recruitment of ITG
and FFG were observed in the Perceptual Discrimination task. These findings
illuminate the contrasting functions of the dorsal and ventral visual streams, to
support rapid shifts of attention in response to contextual landmarks, and
conscious discrimination, respectively.
PMID- 28688856
TI - Implementation of Left Ventricular Ejection Fraction Assessment by Three
Dimensional Echocardiography in Daily Clinical Practice.
PMID- 28688855
TI - Low Incidence of Congenital Bicuspid Aortic Valve in Sub-Saharan African
Children.
PMID- 28688858
TI - A Comprehensive Review of Stress Testing in Hypertrophic Cardiomyopathy:
Assessment of Functional Capacity, Identification of Prognostic Indicators, and
Detection of Coronary Artery Disease.
AB - Hypertrophic cardiomyopathy is a heterogeneous condition that may present with
functional limitation due to dyspnea on exertion, angina, or symptoms of heart
failure. Although angina is a common symptom, it is thought to be multifactorial,
including abnormal microvasculature and epicardial coronary artery disease. The
role of stress testing in the detection of coronary artery disease and its
limitations are discussed in this review. Stress testing yields additional
information beyond the detection of ischemia, which is prognostic independent of
the presence of coronary artery disease and can be beneficial in defining the
presence of provocable left ventricular outflow tract obstruction, symptoms,
response of heart rate and blood pressure to exercise, and functional capacity.
Additional noninvasive imaging techniques, including speckle-tracking
echocardiography and coronary flow velocity reserve, positron emission
tomographic myocardial blood flow, delayed enhancement on cardiac magnetic
resonance imaging, and computed tomographic angiography, are also discussed.
PMID- 28688857
TI - Three-Dimensional Echocardiographic Automated Quantification of Left Heart
Chamber Volumes Using an Adaptive Analytics Algorithm: Feasibility and Impact of
Image Quality in Nonselected Patients.
AB - BACKGROUND: Although 3D echocardiography (3DE) allows accurate and reproducible
quantification of cardiac chambers, it has not been integrated into clinical
practice because it relies on manual input, which interferes with workflow. A
recently developed automated adaptive analytics algorithm for simultaneous
quantification of left ventricular and atrial (LV, LA) volumes was found to be
accurate and reproducible in patients with good images. We sought to
prospectively test its feasibility and accuracy in consecutive patients in
relationship with image quality and reader experience. METHODS: Three hundred
consecutive patients underwent 3DE. Image quality was graded as poor, adequate,
or good. Images were analyzed by an expert echocardiographer to obtain LV volumes
and ejection fraction (EF) and LA volume using the automated analysis
(HeartModel, Philips, Andover, MA) with and without editing the endocardial
boundaries and using conventional manual tracing (QLAB, Philips, Andover, MA)
blinded to the automated measurements as a reference. In a subgroup of 100
patients, automated analysis was repeated by two readers without 3DE experience.
RESULTS: Automated analysis failed in 31/300 patients (10%). Patients with poor
image quality (n = 72, 24%) showed suboptimal agreement with the reference
technique, especially for LVEF. Importantly, patients with adequate (n = 89, 30%)
and good (n = 108, 36%) images showed small biases and excellent correlations
without border corrections, which were further improved with editing. In
contrast, border corrections by inexperienced readers did not improve the
agreement with reference values. CONCLUSIONS: Automated 3DE analysis allows
accurate quantification of left-heart size and function in 66% of consecutive
patients, while in the remaining patients, its performance is limited/unreliable
due to image quality. Border corrections require 3DE experience to improve the
accuracy of the automated measurements. In patients with sufficient image
quality, this automated approach has the potential to overcome the workflow
limitations of the 3D analysis in clinical practice.
PMID- 28688859
TI - Authors' Reply.
PMID- 28688860
TI - Bleeding during laparoscopic gastric bypass surgery as a risk factor for less
favorable outcome. A cohort study from the Scandinavian Obesity Surgery Registry.
AB - BACKGROUND: Intraoperative adverse events are known to be associated with
postoperative complications; however, little is known about whether or not blood
loss during laparoscopic gastric bypass surgery affects the outcome. OBJECTIVE:
To see if intraoperative bleeding was associated with a less favorable outcome,
and to identify patient-specific risk factors for intraoperative bleeding.
SETTING: Nationwide, Sweden. METHODS: Patients who underwent laparoscopic gastric
bypass surgery between January 8, 2007, and September 15, 2015, were included in
the study. The volume of intraoperative blood loss was compared with data from
follow-up at day 30 and 1 and 2 years after surgery. Patient-specific factors
were analyzed as potential risk factors for intraoperative bleeding. RESULTS: The
study included 43,157 patients. Intraoperative bleeding was associated with an
increased risk for postoperative complication (100-499 mL, odds ratio [OR] 2.97,
95% confidence interval [95%CI] 2.53-3.50;>500 mL OR 3.34, 95%CI 2.05-5.44),
lower weight loss (<100 mL, 82.4+/-24.19% excess body mass index-loss [%EBMIL];
100-499 mL, 76.9+/-24.24 %EBMIL, P<.0001;>500 mL 76.9+/-23.89 %EBMIL, P = .063)
and lower reported quality-of-life 2 years after surgery (<100 mL, Obesity
related Problem scale (OP) 21.1+/-24.46; 100-499 mL, OP 25.0+/-26.62, P =
.008;>500 mL, OP 25.2+/-24.46, P = .272). Diabetes (OR 1.30, 95%CI 1.08-1.58),
age (OR 1.02, 95%CI 1.02-1.03), and body mass index (OR 1.03, 95%CI 1.02-1.05)
were patient-specific risk factors for intraoperative bleeding>=100 mL, whereas
intentional preoperative weight loss was associated with a lower risk (OR .50,
95%CI .43-.57). CONCLUSION: Intraoperative bleeding was associated with less
favorable outcome after laparoscopic gastric bypass surgery. Age, body mass
index, and diabetes were risk factors for intraoperative bleeding, while
preoperative weight reduction seems to be protective.
PMID- 28688861
TI - Fluorescence based characterization of early oral squamous cell carcinoma using
the Visually Enhanced Light Scope technique.
AB - OBJECTIVES: Several diagnostic tools have been developed to assess benign and
potentially malignant disorders of soft tissues. In this study, we aimed to
assess the value of the VELscope(r) (Visually Enhanced Light Scope) imaging
device as a technical tool to investigate malignant lesions of the oral cavity.
MATERIAL AND METHODS: In this retrospective study we analyzed the photographs of
90 patients who suffered from malignant oral soft tissue lesions or carcinoma in
situ (CIS) from 2008 to 2014 in the Clinic of Oral and Maxillofacial Surgery of
LMU in Munich. RESULTS: In 85.6% of the cases fluorescence quenching/loss could
be detected. The average value for the colour red shows a significant difference
in pathologic and physiologic tissues (p = 0.007) with a higher median for
pathologic tissues. For the colours green and blue our measurements show
significantly higher values in the healthy tissue (p < 0.001.). The shade of red
showed significantly higher values for pathologic tissues when compared to all
three colours (p < 0.001). Furthermore, the shades of green and blue showed
significantly lower values in the pathologic tissue (p < 0.001). CONCLUSION: In
the near future, VELscope(r) could help to a greater extent than visual
observation alone in identifying the margins of tumor resections. VELscope(r)
still lacks the ability to identify the overall risk level of oral lesions.
PMID- 28688862
TI - Programmable cells of monocytic origin as a source of osteochondroprogenitors:
Effect of growth factors on osteogenic differentiation.
AB - We have demonstrated previously that peripheral blood monocytes can be converted
in vitro to a multipotent stem cell-like cell termed programmable cell of
monocytic origin (PCMO) and subsequently into cells with chondrocyte-like
phenotype. Here, we investigated whether PCMO could also be differentiated into
osteoblast-like cells using growth factors with known osteoinductive potency.
Following stimulation with BMP-2, BMP-7, IGF-1 or TGF-beta1 for 7 and 14 days,
PCMOs were analyzed for mRNA expression of collagen types I and V, alkaline
phosphatase, osteocalcin, runt-related transcription factor-2 (Runx2) and Osterix
(Osx) by quantitative RT-PCR (qPCR) and the levels of collagen I in culture
supernatants by ELISA. The expression of osteoblastic markers was evident, albeit
at a different extent in cultures of PCMOs after treatment with the above
mentioned growth factors. Culture supernatants from PCMOs stimulated for 6-10
days with BMP-2, BMP-7, IGF-1 or TGF-beta1 contained high levels of collagen type
I, together with earlier data indicating synthesis and proper secretion. The
findings suggest that PCMOs can transform into cells that are phenotypically
similar to osteoblasts and identify these cells as osteochondroprogenitors. The
possibility of differentiating PCMOs from peripheral blood in sizable quantities
could be a novel way to obtain autologous bone-like substitutes without donor
site morbidity.
PMID- 28688863
TI - Some innovative evolutions in surgery of the cranio-maxillofacial skeleton.
PMID- 28688864
TI - An objective assessment of botulinum toxin type A injection in the treatment of
post-facial palsy synkinesis and hyperkinesis using the synkinesis assessment
questionnaire.
AB - This study aimed to provide reliable and valid evidence that botulinum toxin type
A (BTX-A) is a successful treatment for facial synkinesis in facial palsy by
using the synkinesis assessment questionnaire (SAQ) tool. Fifty-one patients
completed questionnaires pre- and post-BTX-A treatment over 103 cycles of
treatment. Each patient was individually assessed and then treated according to
their presenting symptoms with a dosage in each injection site of between 0.5 and
5 U of BTX-A. A two-tailed paired samples t-test was used to compare the scores
for each question before and after treatment. A significant difference was found
between all scores before and after treatment at the level of p < 0.05. There was
not only an improvement in the mean score in the post-treatment group but also a
smaller spread of scores in the post-treatment group than in the pre-treatment
group. The study showed that SAQ scores decreased significantly for every
question on the SAQ after treatment. This indicates that BTX-A is an effective
treatment for synkinesis, adding further weight to current evidence. The study
also indicated that BTX-A continues to be effective even after three rounds of
treatment, with a significant decrease in overall scores after each treatment
cycle.
PMID- 28688865
TI - Commentary on "The new opt-out Dutch national breast implant registry - Lessons
learnt from the road to implementation".
PMID- 28688866
TI - A retrospective study: Can we differentiate between repeat self-inflicted burn
patients and those who commit a self-inflicted burn as an individual occurrence?
AB - Self-inflicted burns (SIBs) are a significant cause of burns morbidity worldwide.
A sub-group of SIB patients demonstrate recurrent SIB behaviour causing repeated
morbidity and an increasing strain on hospital resources. The ability to predict
which patients are likely to demonstrate repeat behaviour will allow for more
targeted interventions in this group. This study aimed to identify the factors
that differentiate patients who repeat SIB from those who commit SIB as an
individual occurrence. A three-step approach was adopted: (1) initial data
collection through the locally held records of the International Burns Injury
Database (iBID); (2) follow-up data of SIB patient information were extracted
from patient notes and (3) statistical data analysis. Seventy-five records
remained for analysis. Seventeen patients were identified as going on to commit
SIB more than once and so classified as 'repeat SIB' patients (22.7%). Repeat SIB
patients appeared to be more commonly female and Caucasian with a mean total body
surface area of less than half the individual occurrence group. The repeat SIB
group was also more likely to commit burns to their limbs and demonstrate
previous non-burn deliberate self-harm behaviour. 'Cold' burns were also
committed more commonly in the repeat SIB group. This paper describes the largest
sample of repeat SIB patients in the literature. It appears that repeat SIB
patients have a set of differentiating factors that, when combined, allow for
some element of prediction of these behaviours.
PMID- 28688867
TI - Response to comments on: A prospective randomized cost billing comparison of
local fasciocutaneous perforator versus free Gracilis flap reconstruction for
lower limb in a developing economy.
PMID- 28688868
TI - The effect of dual-sided breast surgery on breast asymmetry: A retrospective
clinical evaluation study.
PMID- 28688869
TI - Ankylosis of temporomandibular joints after mandibular distraction osteogenesis
in patients with Nager syndrome: Report of two cases and literature review.
AB - Nager syndrome, also known as Nager acrofacial dysostosis, was first described by
Nager and de Reynier in 1948. The patients commonly present with micrognathia,
and a preventive tracheostomy is necessary when there are symptoms of upper
airway obstruction. Mandibular distraction osteogenesis is considered as an
effective procedure, which not only improves micrognathia but also minimizes the
chances of tracheostomy. However, mandibular distraction osteogenesis has some
complications such as relapse, teeth injury, infection, and injury of the
temporomandibular joints (TMJs). In this study, the author reported two patients
with Nager syndrome who suffered from ankylosis of TMJs after mandibular
distraction osteogenesis. In addition, a comprehensive literature review of post
distraction ankylosis of TMJs in patients with Nager syndrome was performed. Few
studies demonstrated the condition of TMJs after mandibular distraction
osteogenesis, and three studies were identified from the review. One study
reported ankylosis of bilateral coronoid processes, in which coronoidectomies
were necessary. Another study reported the use of prostheses to replace the
ankylosed joints in a patient who had undergone many surgeries of the joints,
such as gap arthroplasties, reconstructions with costochondral grafts, etc. One
other study raised the concept of unloading the condyles during the mandibular
distraction to prevent subsequent ankylosis. It seems that multiple factors are
related to the ankylosis of TMJs after mandibular distraction osteogenesis in
patients with Nager syndrome. Prevention of post-distraction ankylosis of the
joints is important because the treatment is difficult and not always effective.
We should conduct more studies about protection of the joints during mandibular
distraction in the future.
PMID- 28688870
TI - A prospective randomized cost billing comparison of local fasciocutaneous
perforator vs free Gracilis flap for lower limb reconstruction.
PMID- 28688871
TI - The Lateral Habenula and Adaptive Behaviors.
AB - The evolutionarily conserved lateral habenula (LHb) enables dynamic responses to
continually changing contexts and environmental conditions. A model is proposed
to account for greater mnemonic and contextual control over LHb-mediated response
flexibility as vertebrate brains became more complex. The medial prefrontal
cortex (mPFC) provides instructions for context-specific responses to LHb, which
assesses the extent to which this response information matches the motivation or
internal state of the individual. LHb output either maintains a prior response
(match) or leads to alternative responses (mismatch). It may also maintain
current spatial and temporal processing in hippocampus (match), or alter such
activity to reflect updated trajectory and sequenced information (mismatch). A
response flexibility function of the LHb is consistent with poor behavioral
control following its disruption (e.g., in depression).
PMID- 28688872
TI - Paraganglioma of the Urinary Bladder: A Series of 22 Cases in a Single Center.
AB - OBJECTIVE: Paraganglioma of the urinary bladder (PUB) is rare in bladder cancer,
and currently, a study examining large number of cases from a single center has
not been reported. This study aimed to present the clinical features, treatments,
pathological characteristics, and prognosis of PUB. PATIENTS AND METHODS: From
January 2006 to June 2016, 22 patients were pathologically diagnosed with PUB in
our hospital. Their clinical records, operative notes, pathological reports, and
follow-up records were retrospectively reviewed. RESULTS: The incidence of PUB in
patients with bladder cancer was 0.92%. The mean age at diagnosis was 49.8 +/-
14.6 years (range, 16-76 years) and the male to female ratio was 1:1. Fourteen
cases (63.6%) were functional. The common indicative symptoms included hematuria
(36.4%), hypertension (31.8%), micturition syncope (27.3%), headache (18.2%), and
palpitation (13.6%). All neoplasms were completely resected via transurethral
resection of bladder tumor (TURBT), en bloc transurethral resection with thulium
yag laser, or partial cystectomy. Most PUB samples were positive for
immunohistochemical (IHC) staining markers such as chromogranin A (CgA),
Synaptophysin (Syn), CD56, and S-100 protein, while negative for IHC markers such
as cytokeratins (CKs) and Melan A. According to pathological reports, 72.7% of
PUB cases were at stage T2, 18.2% at T3, and 9.1% at T4. Two cases (9.1%) with
metastasis were malignant. Two patients (9.1%) were lost during follow-up, and
the remaining 20 patients were followed up for a period of 67.8 +/- 38.5 months
(range, 6-130 months). Among them, 16 patients (80%) recovered after the surgery,
1 patient (5%) died of natural causes. PUB recurred in 3 patients (15%), and 1
patient among them died of PUB. CONCLUSION: Despite the rarity, PUB should be
suspected in patients with unexplained symptoms such as micturition syncope,
hematuria, hypertension, headache, or palpitation. Surgery and adjuvant therapies
are effective treatments for PUB. Compared with open surgery, laparoscopic
partial cystectomy and robot-assisted laparoscopic partial cystectomy are
advantageous in the treatment of PUB. Long-term follow-up is recommended for
patients with PUB.
PMID- 28688873
TI - Extracorporeal Shockwave Therapy for Peripheral Arterial Disease: A Review of the
Potential Mechanisms of Action.
AB - BACKGROUND: Lower limb peripheral arterial disease (PAD) affects 20% of
population over 65 years. Extracorporeal shockwave therapy (ESWT) has recently
emerged as a novel, safe, and effective treatment option. This review aims to
assess the mechanism of action by which ESWT improves symptoms in patients with
PAD. METHODS: MEDLINE and EMBASE databases were searched in line with Preferred
Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Any article
investigating the mechanism of action of ESWT in PAD was considered for
inclusion. RESULTS: The systematic review of the current literature yielded 8
relevant articles reporting studies on animal models of hind limb ischemia or on
patients with PAD. These articles described the effects of ESWT on angiogenesis,
arteriogenesis, vasculogenesis, endothelial nitric oxide synthase, lower limb
micro/macrocirculation, and atherosclerosis. CONCLUSION: ESWT increases the
expression of angiogenic, arteriogenic, and vasculogenic factors, reduces vessel
wall stenosis, and improves limb perfusion. However, most of the evidence is
based on animal studies. Future research should focus on elucidating the
mechanism of action of ESWT in PAD patients.
PMID- 28688874
TI - The Role of Endothelial Dysfunction and Inflammation in Chronic Venous Disease.
AB - Chronic venous disease is a potentially prevalent and debilitating condition
affecting millions of individuals, mostly in Western world. Predisposing genetic
and environmental factors contribute to its development. However, the main
etiology remains to be elucidated. An extensive literature search was conducted
in Medline using the following key words algorithm: ("Chronic venous disease" OR
"Chronic venous insufficiency" OR "varicose veins") AND ("endothelial
dysfunction" OR "inflammation"). Besides being a multifactorial disease, it is
now recognized that the hallmark of chronic venous disease pathophysiology likely
remains in inflammation, possibly triggered by sustained venous hypertension and
valvular incompetence. Shear stress changes are directly sensed by endothelial
cells, leading to its activation and subsequent recruitment of leukocytes and
release of proinflammatory agents. Dysfunctional endothelium has a pivotal role
perpetuating the inflammatory cascade, with consequent pathological venous
changes and chronic venous disease worsening. Endothelial dysfunction may be the
central player in the link between varicose veins and deep vein thrombosis. In
this article, we aim to analyze the crucial role of endothelial activation in the
persistent inflammatory cycle that characterizes chronic venous disease.
PMID- 28688875
TI - Diagnostic, Surgical, and Postoperative Challenges of Neuroendocrine Tumors of
the Neck: Clinical Experience and Literature Review.
AB - BACKGROUND: Neuroendocrine tumors of the neck are rare swellings, which
constitute about 0.03% of all tumors. Most are sporadically arising
paragangliomas. Over 50% arise from the carotid bodies and pose difficulties in
diagnosis and surgical management, which may result in disabling complications.
OBJECTIVE: To determine the diagnostic, surgical, and postoperative challenges,
and how to overcome them, in the management of neuroendocrine tumors of the neck.
STUDY DESIGN: Descriptive case series. METHODS: A retrospective analysis of 19
patients who presented to our surgery clinics between 2010 and 2015 with neck
swelling and suspicion of neurogenic tumors were included in the study. All
patients received preoperative evaluation with Doppler studies and neck computed
tomography scan, with the finding of suspicion of neurogenic tumor. Preoperative
tissue diagnosis was not attempted as this usually required excisional biopsy.
All tumors were surgically excised. Data regarding mean tumor size, neurovascular
invasion, postoperative complications, and histopathological findings were
recorded and statistically analyzed. RESULTS: Nineteen patients (7 male) with
median age of 45 years were included. Mean size of the tumor was 7.5 cm (range:
4.0-11.8 cm). Six of the tumors were right sided and 13 left sided. Clinical
findings often were nonspecific and mimicked other conditions. Operative
challenges were encountered in 11 (57.9%) patients, who had tumors of more than 5
cm. Vascular invasion was found in 2 (10.5%) patients, but bleeding requiring
preoperative transfusion was not required in any patient. Neurological
complications occurred in 11 (57.8%) patients; 3 had transit hypoglossal nerve
palsy, with full recovery; 2 had complete nerve palsy, with reasonable
rehabilitation without further surgical intervention; and 5 developed
neurological deficits (hoarseness, dysphagia, or Horner's syndrome) but recovered
and compensated well without further operation. Two patients who had vascular
invasion required vascular reconstruction. Histopathology in 14 (73.7%) cases was
carotid body tumor and 5 were Schwannomas (1 vagal and 4 sympathetic chain). All
4 patients with Schwannomas of cervical sympathetic chain developed Horner's
syndrome; 2 of them have compensated well with reasonable recovery; 2 have had
tarsorrhaphy for cosmetic reasons. The patient with vagal Schwannoma developed
hoarseness and swallowing difficulties, which resolved without intervention. No
malignancy was encountered in this series, and there was no mortality.
CONCLUSIONS: Neuroendocrine tumors of the neck present diagnostic challenges
because of nonspecific clinical findings mimicking other conditions. Preoperative
tissue diagnosis is mostly unsuccessful, and exact diagnosis requires excisional
biopsy. Surgical excision, which is the main treatment, often has associated
technical difficulties and unavoidable complications requiring further
intervention.
PMID- 28688876
TI - Concomitant Coil Embolization for Gutter Leak during Endovascular Aortic Repair
with the Snorkel Technique.
AB - Snorkel endovascular aortic repair (SEVAR) is reported to be effective for the
treatment of pararenal or juxtarenal aortic aneurysms. SEVAR can be performed
with an off-the-self device, which is applied for emergency cases. However, there
is a concern that SEVAR lead to gutter leak due to insertion of multiple stents.
Previously, we performed 2-staged treatment for gutter leak after SEVAR. However,
the gutter leaks can also occur late, and it is often difficult to close.
Therefore, if a significant gutter leak is identified intraoperatively,
performing concomitant gutter coil embolization at the time of the initial
surgery may be reasonable.
PMID- 28688877
TI - Splenic and Pancreatic Abscesses Associated with In Situ Thrombosis of Splenic
Artery.
AB - Splenic infarction is rare and occurs when the splenic artery or its branches
become occluded, either by an embolus or by in situ thrombosis. In situ
thrombosis of splenic artery leading to splenic and pancreatic abscess formation
after infarction is rare. We here present a case of a 65-year-old man who was
found to have acute complete splenic and distal pancreatic infarction and abscess
formation attributable to in situ thrombosis of splenic artery.
PMID- 28688878
TI - Retrospective Review of Billowing Phenomenon-A Mimic of Endoleak Following
Placement of Endologix Covered Stent for the Treatment of Abdominal Aortic
Aneurysm.
AB - BACKGROUND: Billowing is a unique computed tomography (CT) finding of the
Endologix stent graft where a rim of contrast is observed outside the stent's
endoskeleton but still contained within the graft cover. The purpose of this
study is to evaluate the incidence and clinical outcome of billowing following an
Endologix stent-graft placement. METHODS: All patients who underwent abdominal
aortic aneurysm (AAA) repair with endovascular placement of an Endologix stent
graft from January 2002 to September 2013 and who were followed with imaging were
included in the study. The images were evaluated for the incidence of billowing.
Demographics and clinical outcomes were also analyzed. RESULTS: One hundred
twenty-two patients received an Endologix stent graft for AAA repair at our
institution. One hundred patients qualified for this study. Eighty-four patients
had billowing with the majority (70 patients) having crescentic billowing, and
the remaining 14 patients having focal outpouching. Average billowing thickness
measured 4.2 mm (range 1-13). Sixty-three patients with billowing had multiple
follow-up CT angiograms to allow serial monitoring. Twelve patients had
resolution of billowing, 11 patients had reduction in billowing size, 14 patients
had no change in billowing size, and 26 patients had increase in billowing size.
Patients with billowing had a statistically significant reduction in aneurysm sac
size in anteroposterior and transverse dimensions (P = 0.014 and 0.009,
respectively). Five cases of billowing were misdiagnosed as endoleak. Nineteen
true endoleaks were identified, of which 13 cases were associated with billowing.
CONCLUSIONS: Billowing does not seem to be associated with increased morbidity,
mortality, increase in aneurysm size, or presence of endoleak. Billowing should
be recognized as a common and benign finding of the Endologix stent.
PMID- 28688879
TI - Sympathetic Denervation Using Endovascular Radiofrequency Ablation in Patients
with Thromboangiitis Obliterans (Buerger's Disease).
PMID- 28688880
TI - IgG3 subclass: A possible trigger of mixed cryoglobulin cascade in hepatitis C
virus chronic infection.
AB - HCV is a hepatotropic and lymphotropic virus and is the most frequent cause of
"benign" mono-oligoclonal B-lymphocyte proliferation, observed in mixed
cryoglobulinemia (MC). The study aims to investigate the presence, prevalence and
characteristics of the subclasses of cryoglobulins in HCV-patients to look for a
relationship with MC. Fifty HCV-infected patients with cryoglobulins were
enrolled. IgG subclasses were characterized in cryoprecipitate, and serum IgG and
IgM Rheumatoid Factor (RF) were determined. Patients were stratified into two
subgroups according to the presence of IgG3 subclass. Differences were observed
in supernatant IgM, IgG3-positive and IgG3-negative patients with a higher IgM
concentration in the IgG3-negative cohort (p=0.03). Higher IgM-RF was detected in
the IgG3-negative group (p=0.01). IgG3-positive group showed higher IgG-RF
compared to the IgG3-negative group (p<0.0001). IgG3-negative/monoclonal-IgM
patients had higher cryocrit compared to IgG3-negative/polyclonal-IgM patients
(p<0.01). C4 levels were higher in the polyclonal-IgM group compared to
monoclonal-IgM group (p<0.01). We speculate that cryoglobulins are part of a
progressive clonal selection process in which, B-cells are stimulated to produce
oligoclonal IgG3 with RF activity. The persistence of the antigenic stimulus
elicits the production of polyclonal IgM-RF and subsequently the formation of
oligoclonal IgG/polyclonal IgM containing cryoglobulins. In the last stage, a
monoclonal IgM-RF clone is formed which may coexist with a monoclonal IgG3-RF
clone.
PMID- 28688881
TI - The abdominal skin of female Sprague-Dawley rats is more sensitive than the back
skin to drug-induced phototoxicity.
AB - In vivo phototoxicity studies are important to predict drug-induced phototoxicity
in humans; however, a standard methodology has not established. To determine
differences in sensitivity to drug-induced phototoxicity among various skin
sites, we evaluated phototoxic reactions in the back and abdominal skin of female
Sprague-Dawley rats orally dosed with phototoxic drugs (pirfenidone, 8
methoxysoraren, doxycycline, and lomefloxacin) or a non-phototoxic drug
(gatifloxacin) followed by solar-simulated light irradiation comprising 18J/cm2
ultraviolet A. Tissue reactions were evaluated by macroscopic and microscopic
examination and immunohistochemistry for gamma-H2AX, and tissue concentrations of
pirfenidone, doxycycline, and lomefloxacin were measured by tandem mass
spectrometry. In addition, the thicknesses of the skin layers at both sites were
measured in drug-naive rats. The abdominal skin showed more severe reactions to
all phototoxic drugs than the back skin, whereas the minimal erythema dose in
drug-naive rats and skin concentrations of each drug were comparable between the
sites. Furthermore, histopathological lesions and gamma-H2AX-positive cells in
the abdominal skin were detected in deeper layers than in the back skin. The
stratum corneum and dermis in the abdominal skin were significantly thinner than
in the back skin, indicating a difference in the depth of light penetration and
potentially contributing to the site differences observed in sensitivity to
phototoxicity. Gatifloxacin did not induce any phototoxic reactions at either
site. In conclusion, the abdominal skin is more sensitive to drug-induced
phototoxicity than the back skin and may represent a preferable site for
irradiation in this rat phototoxicity model.
PMID- 28688882
TI - Neuroimaging in animal models of epilepsy.
AB - Epilepsy is one of the most common chronic neurological conditions worldwide. The
current poor understanding and lack of reliable biomarkers of the epileptogenic
process are the major limitations in the development of anti-epileptic drugs that
are able to prevent or modify the underlying disease. The rapid progress in
advanced imaging technologies has expanded our opportunities to study the disease
in animal models of epilepsy by means of non-invasive research tools. Here we
review the advances of different in vivo imaging techniques, including magnetic
resonance-based and nuclear imaging-based modalities, in animal models of
epilepsy. Together these techniques can be applied to visualize and quantify
structural, metabolic, functional and molecular changes in longitudinal study
designs to provide unique information about early pathophysiological changes and
their interplay involved in epileptogenesis, monitoring the disease progression,
assessing the effectiveness of possible therapies, and potentially identify
translatable biomarkers for clinical use.
PMID- 28688883
TI - Validity and Interrater Reliability of the Visual Quarter-Waste Method for
Assessing Food Waste in Middle School and High School Cafeteria Settings.
AB - BACKGROUND: Measuring food waste (ie, plate waste) in school cafeterias is an
important tool to evaluate the effectiveness of school nutrition policies and
interventions aimed at increasing consumption of healthier meals. Visual
assessment methods are frequently applied in plate waste studies because they are
more convenient than weighing. The visual quarter-waste method has become a
common tool in studies of school meal waste and consumption, but previous studies
of its validity and reliability have used correlation coefficients, which measure
association but not necessarily agreement. OBJECTIVE: The aims of this study were
to determine, using a statistic measuring interrater agreement, whether the
visual quarter-waste method is valid and reliable for assessing food waste in a
school cafeteria setting when compared with the gold standard of weighed plate
waste. METHODS: To evaluate validity, researchers used the visual quarter-waste
method and weighed food waste from 748 trays at four middle schools and five high
schools in one school district in Washington State during May 2014. To assess
interrater reliability, researcher pairs independently assessed 59 of the same
trays using the visual quarter-waste method. Both validity and reliability were
assessed using a weighted kappa coefficient. RESULTS: For validity, as compared
with the measured weight, 45% of foods assessed using the visual quarter-waste
method were in almost perfect agreement, 42% of foods were in substantial
agreement, 10% were in moderate agreement, and 3% were in slight agreement. For
interrater reliability between pairs of visual assessors, 46% of foods were in
perfect agreement, 31% were in almost perfect agreement, 15% were in substantial
agreement, and 8% were in moderate agreement. CONCLUSIONS: These results suggest
that the visual quarter-waste method is a valid and reliable tool for measuring
plate waste in school cafeteria settings.
PMID- 28688884
TI - Nutrition Screening: Coding after Discharge Underestimates the Prevalence of
Undernutrition.
PMID- 28688885
TI - Using the Systems-Practice Framework to Understand Food Allergen Management
Practices at College Catering Operations: A Qualitative Study.
AB - BACKGROUND: The number of individuals with food allergies or intolerances
attending catered university residential colleges is increasing, and safe dining
options are required to minimize the risk of allergic reactions and food-induced
death. OBJECTIVE: This qualitative research study sought to advance professional
knowledge of the factors affecting allergen management practices, particularly
pertaining to college foodservices. DESIGN: Three catered residential colleges
affiliated with a major university in New Zealand were selected as research
sites. The study used an ethnographic approach and systems-practice theory as a
framework for data collection and organizing results. Data collection techniques
included document analyses (3 hours per site), observations (6 to 8 hours per
site), focus groups with foodservice workers (30 to 45 minutes per site, n=16),
and interviews with foodservice managers (45 to 90 minutes per interview, n=5).
Notes and transcripts were coded through the process of thematic analysis using
NVivo for Mac software, version 11.1.1, to identify factors affecting allergen
management practices. RESULTS: The main factors affecting allergen management
practices at college foodservices included information provided by residents
about dietary requirements; communication between residents and foodservice
staff; systems for allergen management; attitude of foodservice staff; and
college size. CONCLUSIONS: Detailed dietary information, effective communication
with residents, sufficient resources, clarification of responsibilities, and
thorough systems are required for staff to perform safe allergen management
practices. Ultimately, successful implementation was predominantly determined by
staff attitude. Foodservice managers are advised to identify motivators and
address barriers of staff attitudes toward allergen management practices to
promote successful implementation.
PMID- 28688886
TI - Antileukemic ancistrobenomine B and related 5,1'-coupled naphthylisoquinoline
alkaloids from the Chinese liana Ancistrocladus tectorius.
AB - A striking feature of the metabolite pattern of the Southeast Asian liana
Ancistrocladus tectorius (Ancistrocladaceae) is the predominance of 5,1'-coupled
naphthylisoquinoline alkaloids. About 20 alkaloids of this coupling type have so
far been discovered in this plant species. Here, we report on the isolation of
four new 5,1'-linked naphthylisoquinolines from the twigs and stems of A.
tectorius. Two of them, the ancistrobenomines B (5) and C (6), belong to the very
rare group of alkaloids with a fully dehydrogenated isoquinoline portion.
Likewise unusual for naphthylisoquinoline alkaloids is the presence of a
hydroxymethylene group at C-3. Within the large class of meanwhile ca. 180 such
natural products, this structural peculiarity had so far been known only from two
other representatives isolated from the Malaysian species A. benomensis, and from
one single naphthalene-devoid 3-hydroxymethyleneisoquinoline from A. tectorius.
Seven further 5,1'-linked alkaloids, previously isolated from related Asian and
African Ancistrocladus species, have now been identified for the first time in A.
tectorius. Their structural elucidation was achieved by spectroscopic analysis
including HRESIMS, 1D and 2D NMR, and by chemical (oxidative degradation) and
chiroptical (electronic circular dichroism) methods. Ancistrobenomine B (5)
exhibited moderate effects against Plasmodium falciparum and Trypanosoma brucei
rhodesiense in vitro, and it was found to display strong cytotoxic activities
against drug-sensitive acute lymphoblastic CCRF-CEM leukemia cells and their
multidrug-resistant subline, CEM/ADR5000.
PMID- 28688887
TI - Predicting need for additional CT scan in children with a non-diagnostic
ultrasound for appendicitis in the emergency department.
AB - OBJECTIVE: This study aimed to determine which children with suspected
appendicitis should be considered for a computerized tomography (CT) scan after a
non-diagnostic ultrasound (US) in the Emergency Department (ED). METHODS: We
retrospectively reviewed patients 0-18year old, who presented to the ED with
complaints of abdominal pain, during 2011-2015 and while in the hospital had both
US and CT. We recorded demographic and clinical data and outcomes, and used
univariate and multivariate methods for comparing patients who did and didn't
have appendicitis on CT after non-diagnostic US. Multivariate analysis was
performed using logistic regression to determine what variables were
independently associated with appendicitis. RESULTS: A total of 328 patients were
enrolled, 257 with non-diagnostic US (CT: 82 had appendicitis, 175 no
appendicitis). Younger children and those who reported vomiting or had right
lower abdominal quadrant (RLQ) tenderness, peritoneal signs or White Blood Cell
(WBC) count >10,000 in mm3 were more likely to have appendicitis on CT. RLQ
tenderness (Odds Ratio: 2.84, 95%CI: 1.07-7.53), peritoneal signs (Odds Ratio:
11.37, 95%CI: 5.08-25.47) and WBC count >10,000 in mm3 (Odds Ratio: 21.88, 95%CI:
7.95-60.21) remained significant after multivariate analysis. Considering CT with
2 or 3 of these predictors would have resulted in sensitivity of 94%, specificity
of 67%, positive predictive value of 57% and negative predictive value of 96% for
appendicitis. CONCLUSIONS: Ordering CT should be considered after non-diagnostic
US for appendicitis only when children meet at least 2 predictors of RLQ
tenderness, peritoneal signs and WBC>10,000 in mm3.
PMID- 28688888
TI - Observation of Patients Transitioned to an Oral Loop Diuretic Before Discharge
and Risk of Readmission for Acute Decompensated Heart Failure.
AB - BACKGROUND: Heart failure (HF) is associated with high 30-day readmission rates
and places significant financial burden on the health care system. The aim of
this study was to determine if the duration of observation on an oral loop
diuretic before discharge is associated with a reduction in 30-day HF readmission
in patients with acute decompensated HF (ADHF). METHODS AND RESULTS: This was a
retrospective study of adult patients admitted for ADHF at a large academic
medical center. A total of 123 patients were included. Baseline characteristics
were similar between groups. The primary outcome of 30-day HF readmission
occurred in 11 of 61 patients (18%) observed on an oral loop diuretic for <24
hours and in 2 of 62 patients (3.2%) observed on an oral loop diuretic for >=24
hours (P = .023). Readmissions for 60- and 90-day HF were also significantly
lower in patients observed for >=24 hours (P = .014 and P = .049, respectively).
Associations became stronger after multivariate analysis (P < .001). Observation
for <24 hours and previous admission within 30 days were independent predictors
of 30-day HF readmission (P = .03). CONCLUSIONS: Observation of patients on an
oral loop diuretic for <24 hours was associated with significantly higher 30-day
HF readmission. Therefore, observation on an oral loop diuretic for >=24 hours
before discharge in patients presenting with ADHF should be strongly considered.
PMID- 28688889
TI - Increased Secondary/Primary Bile Acid Ratio in Chronic Heart Failure.
AB - OBJECTIVE: Bile acids (BAs) are now recognized as signaling molecules and
emerging evidence suggests that BAs affect cardiovascular function. The gut
microbiota has recently been linked to the severity of heart failure (HF), and
microbial metabolism has a major impact on BA homeostasis. We aimed to
investigate the pattern of BAs, and particularly microbiota-transformed
(secondary) BAs, in patients with chronic HF. METHODS AND RESULTS: This was a
prospective, observational, single-center study including 142 patients with
chronic HF and 20 age- and sex-matched healthy control subjects. We measured
plasma levels of primary, secondary, and total BAs, and explored their
associations with clinical characteristics and survival. Plasma levels of primary
BAs were lower (P < .01) and the ratios of secondary to primary BAs higher (P <
.001) in patients with HF compared with control subjects. Approximately 40% of
patients in the upper tertile of the ratio of secondary to primary BAs died
during 5.6 years of follow-up (unadjusted Cox regression: hazard ratio 1.93, 95%
confidence interval 1.01-3.68, compared with the lower tertiles). However, this
association was attenuated and no longer significant in multivariate analyses.
CONCLUSIONS: Levels of primary BAs were reduced and specific secondary BAs
increased in patients with chronic HF. This pattern was associated with reduced
overall survival in univariate analysis, but not in multivariate analyses. Future
studies should assess the regulation and potential role of BA metabolism in HF.
PMID- 28688890
TI - Any changes in recent massive transfusion practices in a tertiary level
institution?
AB - BACKGROUND & OBJECTIVES: A previous review of transfusion practices in our
institution between 1998 and 2008 showed a trend of high ratios of red cells (RC)
to plasma (FFP) and platelets to RC towards the later years of review period. The
aim of the study was to further evaluate transfusion practices in the form of
blood product usage and outcomes following massive transfusion (MT) METHODS: All
adult patients with critical bleeding who received a MT (defined as >=10 units of
RC in 24h) in 2008 and between January 2010 and December 2014 were identified.
Blood and blood products transfused, in-hospital mortality, 24h and 90-day
mortality were analysed for the period 2010-2014. Blood and blood product usage,
massive transfusion protocol (MTP) activation and use of ROTEM between 2008 and
2014 were compared. RESULTS: A total of 190 MT including surgical (52.1%), gastro
intestinal bleeding (25.3%), trauma (11.6%) and obstetric haemorrhage (5.8%)
episodes were identified between 2010 and 2014. The overall in-hospital mortality
was 26.7% with a significant difference in 24h (p=0.04) and 90-day mortality
(p=0.02) between diagnostic groups. Comparing 2008 (n=33) and 2014 (n=23), there
was no significant difference in median RC, FFP and platelet units,
cryoprecipitate doses and RC:FFP ratio; however there was an increase in number
of patients who used cryoprecipitate (54.5% vs 87%, p=0.01). CONCLUSION: Aligned
with haemostatic resuscitation, the trend continues in the form of increased use
of plasma and higher RC:FFP transfusion ratios including an increase in number of
patients receiving cryoprecipitate.
PMID- 28688891
TI - Laparoscopic Ureteral Reimplantation for Obstructive Megaureter with Deeply
Infiltrating Endometriosis.
PMID- 28688892
TI - Vascular ossification: Pathology, mechanisms, and clinical implications.
AB - In recent years, the mechanisms and clinical significance of vascular
calcification have been increasingly investigated. For over a century, however,
pathologists have recognized that vascular calcification is a form of heterotopic
ossification. In this review, we aim to describe the pathology and molecular
processes of vascular ossification, to characterize its clinical significance and
treatment options, and to elucidate areas that require further investigation. The
molecular mechanisms of vascular ossification involve the activation of
regulators including bone morphogenic proteins and chondrogenic transcription
factors and the loss of mineralization inhibitors like fetuin-A and
pyrophosphate. Although few studies have examined the gross pathology of vascular
ossification, the presence of these molecular regulators and evidence of
microfractures and cartilage have been demonstrated on heart valves and
atherosclerotic plaques. These changes are often triggered by common inflammatory
and metabolic disorders like diabetes, hyperlipidemia, and chronic kidney
disease. The increasing prevalence of these diseases warrants further research
into the clinical significance of vascular ossification and future treatment
options.
PMID- 28688893
TI - The effects of temperature, activity and convection on the plastron PO2 of the
aquatic bug Aphelocheirus aestivalis (Hemiptera; Aphelocheiridae).
AB - The aquatic bug Aphelocheirus aestivalis (Fabricius 1794) utilises a plastron, a
thin bubble layer on the surface of its body to extract O2 from the water.
Millions of tiny hairs keep the bubble from collapsing, enabling the bug to
remain submerged indefinitely. The development of fibre optic O2-probes has
allowed measurements of O2 pressure (PO2) surrounding the plastron, and within
the plastron although only for short periods. Here we developed methods to
continuously measure plastron PO2, and investigate how it is affected by
temperature (15, 20, 25 degrees C), activity, and water circulation. We also made
measurements of water PO2, temperature and velocity in the field and swimming
velocity at the treatment temperatures. Results show that plastron PO2 is
inversely related to temperature, associated with differences in metabolic
demand, and that small bouts of activity or changes in water convection result in
rapid changes in plastron PO2. A model was developed to calculate the conditions
under which Aphelocheirus would exist without becoming O2-limited in relation to
water temperature, PO2 and boundary layer thickness. This suggests that
Aphelocheirus at one of two field sites may have a reduced metabolic scope even
in well convected water in association with low PO2 and moderate temperature, and
that in well convected, air-saturated water, bugs may have a reduced metabolic
scope where water temperatures are between 20 and 25 degrees C. If exposed to
5kPa PO2, Aphelocheirus cannot sustain resting metabolic rate even in well
convected water and would die at temperatures above approximately 25 degrees C.
PMID- 28688894
TI - A review of keratoconus: Diagnosis, pathophysiology, and genetics.
AB - We discuss new approaches to the early detection of keratoconus and recent
investigations regarding the nature of its pathophysiology. We review the current
evidence for its complex genetics and evaluate the presently identified
genes/loci and potential candidate gene/loci. In addition, we highlight current
research methodologies that may be used to further elucidate the pathogenesis of
keratoconus.
PMID- 28688896
TI - The alteration of autophagy and apoptosis in the hippocampus of rats with natural
aging-dependent cognitive deficits.
AB - AIMS: The present study was aim to explore aging-dependent changes in hippocampal
autophagy and apoptosis in a natural aging rat model from adult to old stages and
to discover a suitable age for treating neurodegenerative diseases. METHODS:
Wistar rats at 5, 18 and 24months of age were used to mimic the adulthood,
initial old, and old phases, respectively. The learning and cognitive ability of
the rats was detected by the Morris water maze test. Morphological changes in the
hippocampus were observed. Expressions of apoptosis and autophagy-related
proteins were examined by Western blot. RESULTS: The adult group (5months)
exhibited high levels of autophagy related p-ULK p-ULK-1/ULK-1 ratio, Beclin-1,
LC3II and cell survival, maintaining normal learning and cognitive function and
integrated hippocampal morphology. The initial old group (18 months) presented a
reduced number of neurons and cognitive deficits, and exhibited high levels of
apoptosis related Bax/Bcl-2 ratio, Caspase-3 activation and autophagy related p
ULK p-ULK-1/ULK-1 ratio, Beclin-1, LC3II compared to the adult group. The old
group (24 months) exhibited a high level of apoptosis related Bax/Bcl-2 ratio,
Caspase-3 activation and a low level of autophagy related p-ULK p-ULK-1/ULK-1
ratio, Beclin-1, LC3II compared to its younger group, as well as significant
neuronal death and cognitive deficits. The degree of autophagy was generally
consistent with its negative regulator, the PI3K/Akt/mTOR axis, in all groups.
CONCLUSION: Our data suggest that cognitive deficits are first observed in the
initial old stage. The levels of autophagy and apoptosis tend to be opposite in
the adult and old phases. High levels of autophagy and apoptosis coexist in the
initial old stage. Our study indicates that up-regulation of autophagy in the
initial old phase to anti-cognitive deficits must be further evaluated.
PMID- 28688895
TI - Differential requirement of SUFU in tissue development discovered in a
hypomorphic mouse model.
AB - Suppressor of Fused (SUFU) is an essential negative regulator of the Hedgehog
(HH) pathway and involved in GLI transcription factor regulation. Due to early
embryonic lethality of Sufu-/- mice, investigations of SUFU's role later in
development are limited to conditional, tissue-specific knockout models. In this
study we developed a mouse model (SufuEx456(fl)/Ex456(fl)) with hypomorphic
features where embryos were viable up to E18.5, although with a spectrum of
developmental defects of varying severity, including polydactyly, exencephaly and
omphalocele. Development of certain tissues, like the skeleton, was more affected
than that of others such as skin, which remained largely normal. Interestingly,
no apparent changes in the dorso-ventral patterning of the neural tube at E9.0
could be seen. Thus, this model provides an opportunity to globally study SUFU's
molecular function in organogenesis beyond E9.5. Molecularly,
SufuEx456(fl)/Ex456(fl) embryos displayed aberrant mRNA splicing and drastically
reduced levels of Sufu wild-type mRNA and SUFU protein in all tissues. As a
consequence, at E9.5 the levels of all three different GLI proteins were reduced.
Interestingly, despite the reduction of GLI3 protein levels, the critical ratio
of the GLI3 full-length transcriptional activator versus GLI3 truncated repressor
remained unchanged compared to wild-type embryos. This suggests that the limited
amount of SUFU protein present is sufficient for GLI processing but not for
stabilization. Our data demonstrate that tissue development is differentially
affected in response to the reduced SUFU levels, providing novel insight
regarding the requirements of different levels of SUFU for proper organogenesis.
PMID- 28688897
TI - Gross motor ability predicts response to upper extremity rehabilitation in
chronic stroke.
AB - The majority of rehabilitation research focuses on the comparative effectiveness
of different interventions in groups of patients, while much less is currently
known regarding individual factors that predict response to rehabilitation. In a
recent article, the authors presented a prognostic model to identify the
sensorimotor characteristics predictive of the extent of motor recovery after
Constraint-Induced Movement (CI) therapy amongst individuals with chronic mild-to
moderate motor deficit using the enhanced probabilistic neural network (EPNN).
This follow-up paper examines which participant characteristics are robust
predictors of rehabilitation response irrespective of the training modality. To
accomplish this, EPNN was first applied to predict treatment response amongst
individuals who received a virtual-reality gaming intervention (utilizing the
same enrollment criteria as the prior study). The combinations of predictors that
yield high predictive validity for both therapies, using their respective
datasets, were then identified. High predictive classification accuracy was
achieved for both the gaming (94.7%) and combined datasets (94.5%). Though CI
therapy employed primarily fine-motor training tasks and the gaming intervention
emphasized gross-motor practice, larger improvements in gross motor function were
observed within both datasets. Poorer gross motor ability at pre-treatment
predicted better rehabilitation response in both the gaming and combined
datasets. The conclusion of this research is that for individuals with chronic
mild-to-moderate upper extremity hemiparesis, residual deficits in gross motor
function are highly responsive to motor restorative interventions, irrespective
of the modality of training.
PMID- 28688898
TI - Liver biopsy findings in patients with hematopoietic cell transplantation.
AB - Liver dysfunction is a frequent complication after hematopoietic cell
transplantation. Liver biopsy has an important role for confirming the diagnosis
of graft-versus-host disease (GVHD) or other liver diseases. The histological
features of GVHD are not specific, and GVHD and other coexisting diseases may be
present in the same biopsy, which makes the histologic interpretation of the
liver biopsy more complex and challenging. The aim of the study is to improve the
present diagnostic criteria. Fifty-two liver biopsies were studied. Most biopsies
(47, 92%) showed some features of GVHD. Five (9.6%) had no GVHD, 20 (38.5%) had
possible GVHD, and 27 (51.9%) had likely GVHD. Histologic features were analyzed
semi-quantitatively and scored. Bile duct damage and intraepithelial lymphocytes
were significantly more frequent in likely GVHD groups. Bile duct injury score
calculated as the sum of bile duct damage and intraepithelial lymphocytes score
was 2.3 in no GVHD and possible GVHD groups, and 4.2 in likely GVHD group
(P<.001). A bile duct injury score >=4 correlated well with a diagnosis of GVHD,
with sensitivity 74% and specificity 88%. Many cases (36; 70.6%) had a concurrent
disease process. Drug-induced liver injury (8, 16%) and sinusoidal obstruction
syndrome (6, 12%) are particularly important causes of liver dysfunction.
Moderate degree of bile duct injury and intraepithelial lymphocytes were the most
helpful histologic findings to confirm the diagnosis of GVHD. In addition, it is
important for the pathologist to be aware of the etiologies of liver dysfunction
other than GVHD.
PMID- 28688900
TI - MiR-34a/sirtuin-1/foxo3a is involved in genistein protecting against ox-LDL
induced oxidative damage in HUVECs.
AB - The antioxidant activity of genistein is associated with preventing
atherosclerosis; however, the underlying mechanisms are not fully understood. In
this study, human umbilical vein endothelial cells (HUVECs) were pretreated with
genistein at different concentrations (10nM, 100nM and 1000nM) for 6h and then
exposed to ox-LDL (50mg/L) for another 24h. Results showed that genistein
restrained reactive oxygen species (ROS) and malondialdehyde (MDA) production,
and ameliorated the inhibitory effect on superoxide dismutase (SOD), catalase
(CAT), glutathione (GSH) and glutathione peroxidase (GPx) activity elicited by ox
LDL stimulation. The effects of genistein were correlated with the upregulation
of sirtuin-1 via inhibiting miR-34a, and were abolished by sirtuin-1 siRNA or miR
34a mimic. Moreover, the antioxidation of genistein was associated with miR
34a/sirtuin-1-mediated nuclear translocation and deacetylation of foxo3a,
accompanying with the enhanced expressions of MnSOD and CAT. The present study
suggests that miR-34a/sirtuin-1/foxo3a might play an important role in genistein
reversing ox-LDL-induced oxidative damage in HUVECs.
PMID- 28688901
TI - MicroRNA-155 regulates arsenite-induced malignant transformation by targeting
Nrf2-mediated oxidative damage in human bronchial epithelial cells.
AB - Arsenite is a well-documented human lung carcinogen but the detailed mechanisms
of carcinogenesis remain unclear. In this study, human bronchial epithelial (16
HBE) cells were continuously exposed to 2.5MUM arsenite for about 13 weeks to
induce the phenotypes of malignant transformation. Our results showed that Nrf2
expression was gradually decreased whereas no significant change was observed on
NF-kappaB activation with increased time of arsenite exposure. To test the roles
of Nrf2-meidtaed oxidative damage in the arsenite-induced malignant
transformation, we compared the levels of cGMP, PKG and oxidative damage-related
indicators between arsenic-transformed cells and control cells. Our data
demonstrated there were no significantly differences on the contents of cGMP,
PKG, MDA and the production of ROS, but the levels of GSH and NO, the activities
of SOD, tNOS and iNOS were significantly enhanced in the arsenic-transformed
cells. Importantly, Nrf2 inactivation could be modulated by miR-155, and
inhibition of miR-155 remarkably attenuated the malignant phenotypes and promoted
apoptotic cell death in the arsenic-transformed cells. Together, our findings
provide the novel mechanism that miR-155 may regulate arsenite-induced cell
malignant transformation by targeting Nrf2-mediated oxidative damage, indicating
that inhibition of miR-155 may be a potential strategy against lung
carcinogenesis of arsenite.
PMID- 28688899
TI - Central insulin dysregulation and energy dyshomeostasis in two mouse models of
Alzheimer's disease.
AB - Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder
worldwide. While the causes of AD are not known, several risk factors have been
identified. Among these, type two diabetes (T2D), a chronic metabolic disease, is
one of the most prevalent risk factors for AD. Insulin resistance, which is
associated with T2D, is defined as diminished or absent insulin signaling and is
reflected by peripheral blood hyperglycemia and impaired glucose clearance. In
this study, we used complementary approaches to probe for peripheral insulin
resistance, central nervous system (CNS) insulin sensitivity and energy
homeostasis in Tg2576 and 3xTg-AD mice, two widely used animal models of AD. We
report that CNS insulin signaling abnormalities are evident months before
peripheral insulin resistance. In addition, we find that brain energy metabolism
is differentially altered in both mouse models, with 3xTg-AD mice showing more
extensive changes. Collectively, our data suggest that early AD may reflect
engagement of different signaling networks that influence CNS metabolism, which
in turn may alter peripheral insulin signaling.
PMID- 28688902
TI - Serum S100 calcium binding protein A4 improves the diagnostic accuracy of
transient elastography for assessing liver fibrosis in hepatitis B.
AB - AIM: The diagnostic performance of Fibroscan might be improved when combined with
other serum fibrosis related markers. Previous study has demonstrated that S100A4
expression is associated with liver fibrosis in humans with hepatitis. This study
aimed to clarify diagnostic accuracy of serum S100A4 levels for significant liver
fibrosis in patients with chronic hepatitis B (CHB), and develop a combined
algorithm of liver stiffness measurement (LSM) and S100A4 to predict significant
liver fibrosis in CHB. METHODS: One hundred and seventy-five CHB patients who had
performed liver biopsy were consecutively included. We evaluated serum S100A4
levels, LSM values and other clinically-approved fibrosis scores. RESULTS: Serum
S100A4 level was higher in CHB patients with significant fibrosis, compared to
those without [199.58 (33.31-1971.96) vs. 107.15 (2.10-1038.94), P<0.001]. Using
receiver-operating characteristic (ROC) analyses, the area under the curves
(AUC), sensitivity, specificity and accuracy of S100A4 were found to be 0.749,
62.7%, 75.9% and 0.70 for significant fibrosis (>=Stage 2), respectively.
Although not superior to LSM, these results were better than the fibrosis index
based on the 4 factor (FIB-4) and the aspartate aminotransferase-to-platelet
ratio index (APRI) for significant fibrosis detection. An algorithm consisting of
S100A4 and LSM was derived. The AUC, sensitivity, specificity and accuracy of
model based on serum S100A4 level and LSM were 0.866, 86.6%, 77.8% and 0.79 for
significant fibrosis detection, superior to those based on LSM alone (0.834,
76.1%, 80.7% and 0.76, P=0.041). CONCLUSION: Serum S100A4 level was identified as
a fibrosis marker of liver fibrosis in patients with CHB. Combining serum S100A4
with LSM improved the accuracy of transient elastography for hepatitis B
significant fibrosis detection.
PMID- 28688903
TI - Differential effects between developmental and postpubertal exposure to N-methyl
N-nitrosourea on progenitor cell proliferation of rat hippocampal neurogenesis in
relation to COX2 expression in granule cells.
AB - This study was performed to compare the exposure effects of N-methyl-N
nitrosourea (MNU), a cytocidal agent of proliferating cells, on rat hippocampal
neurogenesis between developmental and postpubertal periods. Developmental
exposure through maternal drinking water from gestational day 6 to day 21 after
delivery on weaning decreased GFAP-immunoreactive (+) stem cells and increased
immunoreactive cells indicative of subsequent progenitor and postmitotic immature
neuronal populations, TUNEL+ or p21Cip1/Waf1+ stem/progenitor cells and COX2+
granule cells, on postnatal day (PND) 21. On PND 77 after cessation of
developmental exposure, NeuN+ postmitotic granule cells decreased in number.
Postpubertal exposure by oral gavage for 28days decreased the numbers of all
granule cell lineage populations and ARC+ or COX2+ granule cells and increased
the number of TUNEL+ stem/progenitor cells. These results suggested that both
developmental and postpubertal exposure caused apoptosis of stem/progenitor
cells. However, developmental exposure increased COX2 expression to facilitate
intermediate progenitor cell proliferation and increased neuronal plasticity.
This effect was concurrent with the induction of p21Cip1/Waf1 that causes cell
cycle arrest of stem/progenitor cells in response to accumulating DNA damage on
weaning, resulting in a subsequent reduction of postmitotic granule cells. In
contrast, postpubertal exposure suppressed neuronal plasticity as evidenced by
downregulation of ARC and COX2. The COX2 downregulation was responsible for the
lack of facilitating stem/progenitor cell proliferation. Induction of apoptosis
and the lack of cell proliferation facilitation may be responsible for the
overall reduction of neurogenesis caused by postpubertal exposure. Thus, the
disrupted pattern of hippocampal neurogenesis induced by MNU is different between
developmental and postpubertal exposure.
PMID- 28688904
TI - Contributions of individual face features to face discrimination.
AB - Faces are highly complex stimuli that contain a host of information. Such
complexity poses the following questions: (a) do observers exhibit preferences
for specific information? (b) how does sensitivity to individual face parts
compare? These questions were addressed by quantifying sensitivity to different
face features. Discrimination thresholds were determined for synthetic faces
under the following conditions: (i) 'full face': all face features visible; (ii)
'isolated feature': single feature presented in isolation; (iii) 'embedded
feature': all features visible, but only one feature modified. Mean threshold
elevations for isolated features, relative to full-faces, were 0.84x, 1.08, 2.12,
3.34, 4.07 and 4.47 for head-shape, hairline, nose, mouth, eyes and eyebrows
respectively. Hence, when two full faces can be discriminated at threshold, the
difference between the eyes is about four times less than what is required when
discriminating between isolated eyes. In all cases, sensitivity was higher when
features were presented in isolation than when they were embedded within a face
context (threshold elevations of 0.94x, 1.74, 2.67, 2.90, 5.94 and 9.94). This
reveals a specific pattern of sensitivity to face information. Observers are
between two and four times more sensitive to external than internal features. The
pattern for internal features (higher sensitivity for the nose, compared to
mouth, eyes and eyebrows) is consistent with lower sensitivity for those parts
affected by facial dynamics (e.g. facial expressions). That isolated features are
easier to discriminate than embedded features supports a holistic face processing
mechanism which impedes extraction of information about individual features from
full faces.
PMID- 28688905
TI - Long-term motor learning: Effects of varied and specific practice.
AB - According to the schema theory, variability during practice allows for a larger
repertoire of movements to help form a generalized motor program for similar
motor skills. Varied training is thought to enhance long-term retention of the
motor program due to the heightened difficulty presented. In a highly cited study
on this topic, Kerr and Booth (Perceptual and Motor Skills 46 (1978), 395-401)
trained two groups of children for 10weeks to throw a beanbag towards either one
central target (specific group) or two targets that were +/-1 foot away from the
central target (varied group). They found that the varied group performed
significantly better than the specific group when both groups were tested at the
central target. We, following the same paradigm, trained 30 adults on a similar
beanbag throwing task and tested them at various target distances. Our results
suggested that after 5-7weeks of training, the specific groups tended to
undershoot at longer distances and overshoot at shorter distances while the
varied group tended to center their throws around the target at all distances.
However, the overall magnitude of error (regardless of over- or undershooting)
was similar across groups. We found some support for the hypothesis that the
varied group could better generalize to untrained distances, but this advantage
was found mainly for the longest distance and disappeared by a posttest held two
weeks after practice.
PMID- 28688906
TI - Effects of photopic and cirtopic illumination on steady state pupil sizes.
AB - The conventional view was that cones are responsible for pupil constriction in
photopic lighting conditions. With the discovery of intrinsically photosensitive
retinal ganglion cells (ipRGC), it was found that signals from ipRGCs along with
cones mediated the pupil light reflex in photopic lighting conditions. Although
both signals contributed, it was unclear how these signals were summed. In the
work reported here, steady-state pupil size was measured with an infrared camera
under LED lighting conditions with different color temperatures and luminance. A
formula was then derived for pupil size according to the linear summation of
cirtopic and photopic luminance. This formula allowed direct calculations to
predict pupil size well when LED photopic luminance ranged from about 50cd/m2 to
300cd/m2, which is the general luminance level range for computer and smartphone
screens.
PMID- 28688907
TI - Face identity recognition in simulated prosthetic vision is poorer than
previously reported and can be improved by caricaturing.
AB - The visual prosthesis (or "bionic eye") has become a reality but provides a low
resolution view of the world. Simulating prosthetic vision in normal-vision
observers, previous studies report good face recognition ability using tasks that
allow recognition to be achieved on the basis of information that survives low
resolution well, including basic category (sex, age) and extra-face information
(hairstyle, glasses). Here, we test within-category individuation for face-only
information (e.g., distinguishing between multiple Caucasian young men with hair
covered). Under these conditions, recognition was poor (although above chance)
even for a simulated 40*40 array with all phosphene elements assumed functional,
a resolution above the upper end of current-generation prosthetic implants. This
indicates that a significant challenge is to develop methods to improve face
identity recognition. Inspired by "bionic ear" improvements achieved by altering
signal input to match high-level perceptual (speech) requirements, we test a high
level perceptual enhancement of face images, namely face caricaturing
(exaggerating identity information away from an average face). Results show
caricaturing improved identity recognition in memory and/or perception (degree by
which two faces look dissimilar) down to a resolution of 32*32 with 30% phosphene
dropout. Findings imply caricaturing may offer benefits for patients at
resolutions realistic for some current-generation or in-development implants.
PMID- 28688908
TI - Ultra-wide-field imaging in diabetic retinopathy.
AB - Since 1991, 7-field images captured with 30-50 degree cameras in the Early
Treatment Diabetic Retinopathy Study were the gold standard for fundus imaging to
study diabetic retinopathy. Ultra-wide-field images cover significantly more area
(up to 82%) of the fundus and with ocular steering can in many cases image 100%
of the fundus ("panretinal"). Recent advances in image analysis of ultra-wide
field imaging allow for precise measurements of the peripheral retinal lesions.
There is a growing consensus in the literature that ultra-wide-field imaging
improves detection of peripheral lesions in diabetic retinopathy and leads to
more accurate classification of the disease. There is discordance among studies,
however, on the correlation between peripheral diabetic lesions and diabetic
macular edema and optimal management strategies to treat diabetic retinopathy.
PMID- 28688909
TI - Are we making an impact with incident learning systems? Analysis of quality
improvement interventions using total body irradiation as a model system.
AB - PURPOSE: Despite increasing interest in incident learning systems (ILS) to
improve safety and quality in radiation oncology, little is known about
interventions developed in response to safety data. We used total body
irradiation (TBI) as a model system to study the effectiveness of interventions
from our institutional ILS. METHODS AND MATERIALS: Near-miss event reports
specific to TBI were identified from a departmental ILS from March 2012 to
December 2015. The near-miss risk index was rated at multidisciplinary review
from 0 (no potential harm) to 4 (critical potential harm). Interventions were
analyzed for effectiveness with a schema adapted from The Joint Commission and
other agencies: "most reliable" (eg, forcing functions, automation), "somewhat
reliable" (eg, checklists, standardization), and "least reliable" (eg, training,
rules, procedures). Causal factors of each event were drawn from the casual
factor schema used in radiation oncology ILS. RESULTS: Of 4007 safety-related
reports, 266 reports pertained to TBI. TBI reports had a somewhat higher
proportion of high-risk events (near-miss risk index 3-4) compared with non-TBI
reports (25% vs 17%, P = .0045). A total of 117 interventions were implemented.
The reliability indicators for the interventions were: most reliable (11% of
interventions), somewhat reliable (17%), and least reliable (72%). Interventions
were more likely to be applied to high-risk events (54% vs 41%, P = .03). There
was a pattern of high-reliability interventions with increased risk score of
events. Events involving human error (eg, slips) and equipment/information
technology lent themselves more often to high-reliability interventions. Events
related to communication, standardization, and training were associated with low
reliability interventions. CONCLUSIONS: Over a 3.5-year period, 117 quality
improvement strategies were developed for TBI based on ILS. Interventions were
more likely to be applied to high-risk events and high-risk events were more
likely to be associated with high-quality interventions. These results may be
useful to institutions seeking to develop interventions based on ILS data.
PMID- 28688910
TI - Burden of palliative care issues encountered by radiation oncologists caring for
patients with advanced cancer.
AB - PURPOSE: Radiation oncologists frequently provide care for patients with advanced
cancer who are in their last months or weeks of life. This study examined the
previously not well-characterized types and frequencies of palliative care issues
encountered in consultations for palliative radiation therapy (PRT). METHODS AND
MATERIALS: This prospective, survey-based study assessed consecutive consults for
PRT from May 19, 2014, to September 26, 2014 at 3 Boston-area community and
academic, hospital-based centers. Participating physicians and nurse
practitioners completed a survey to identify and rank the relevance (5-point
Likert scale, not at all to extremely) of palliative care issues. Eight domains
adapted from national palliative care guidelines (physical symptoms, psychosocial
issues, cultural considerations, spiritual needs, care coordination, advance care
planning, goals of care, and ethical and legal issues) were evaluated. A total of
162 consecutive consultations were surveyed with 140 responses received (86%
response rate). RESULTS: Most (82%) consults had 2 or more palliative care
domains ranked as highly (very or extremely) relevant to care. The domains of
physical symptoms (91%), care coordination (70%), goals of care (59%), and
psychosocial issues (52%) were the most commonly reported domains as highly
relevant to care. Forty-six percent of consults involved a high palliative care
burden (4 or more palliative care domains identified as highly relevant to care).
Predictors of high palliative care burden in multivariable analysis were Eastern
Cooperative Oncology Group performance status >2 (odds ratio, 3.57; P = .047), a
plan for no further anticancer therapy after PRT (odds ratio, 3.46; P = .03), and
a recommendation against PRT (odds ratio, 4.80; P = .01). CONCLUSIONS: Radiation
oncology clinicians encounter multiple palliative care issues when consulting on
patients for PRT. Clinicians identified physical symptoms, care coordination, and
goals of care as the most relevant palliative care domains. These findings can
help guide palliative care development within radiation oncology, including
education and structures of care delivery.
PMID- 28688911
TI - Evaluation of dietary Hybanthus enneaspermus (Linn F. Muell.) as a growth and
haemato-immunological modulator in Labeo rohita.
AB - This study evaluated the effects of Hybanthus enneaspermus aqueous extract (HEE)
as a feed supplement on growth, immune responses, haematological, and biochemical
parameters of Labeo rohita and its susceptibility to Aeromonas hydrophila
infection. Diets containing five variable concentrations of HEE (g kg-1) (0
[basal diet], 1.0 [H1], 2.0 [H2], 3.0 [H3], and 4.0 [H4]) were fed to fish
(average weight: 17.2 +/- 0.21 g) for 6 weeks. Growth parameters, immune
parameters, and haemato-biochemical parameters were examined 6 weeks post
feeding. The results showed that growth parameters, such as final weight (39.47
+/- 3.1 g) and specific growth rate (1.92 +/- 0.2), were significantly higher in
the H3 group than in the control. Immunological parameters such as serum lysozyme
(24.73 +/- 2.16 U mg-1), phagocytic activity (19.14+/- 0.26%), and respiratory
burst activity (0.307 +/- 0.005) were significantly higher in the H3 group,
compared with the control. Among the haematological parameters examined, red
blood cells, white blood cells, neutrophils, total serum protein, and albumin
levels were significantly higher in the H3 group. However, HEE administration had
no significant effect on haematocrit, haemoglobin, monocytes, or eosinophils
levels. Blood biochemical parameters, including superoxide dismutase and alkaline
phosphatase activities, were higher (P < 0.05) in the H3 group than in the
control; however, the opposite result was found for aspartate transaminase,
alanine transaminase, glucose, and cholesterol. Supplementation with 3 g kg-1 HEE
increased the activities of intestinal digestive enzyme (amylase, protease, and
lipase) in fish. Moreover, fish fed diets supplemented with 3 g kg-1 HEE
exhibited the highest disease resistance against A. hydrophila infection. These
results suggest that dietary administration of HEE (at 3 g kg-1) has several
positive effects on growth, immune and haematological responses in L. rohita.
PMID- 28688912
TI - Inhibition of the kynurenine pathway protects against reactive microglial
associated reductions in the complexity of primary cortical neurons.
AB - Brain glia possess the rate limiting enzyme indoleamine 2, 3-dioxygenase (IDO)
which catalyses the conversion of tryptophan to kynurenine. Microglia also
express kynurenine monooxygenase (KMO) and kynureninase (KYNU) which lead to the
production of the free radical producing metabolites, 3-hydroxykynurenine and 3
hydroxyanthranillic acid respectively and subsequently production of the NMDA
receptor agonist quinolinic acid. The aim of this study was to examine the effect
of IFNgamma-stimulated kynurenine pathway (KP) induction in microglia on neurite
outgrowth and complexity, and to determine whether alterations could be abrogated
using pharmacological inhibitors of the KP. BV-2 microglia were treated with
IFNgamma (5ng/ml) for 24h and conditioned media (CM) was placed on primary
cortical neurons 3 days in vitro (DIV) for 48h. Neurons were fixed and neurite
outgrowth and complexity was assessed using fluorescent immunocytochemistry
followed by Sholl analysis. Results show increased mRNA expression of IDO, KMO
and KYNU, and increased concentrations of tryptophan, kynurenine, and 3
hydroxykynurenine in the CM of IFNgamma-stimulated BV-2 microglia. The IFNgamma
stimulated BV-2 microglial CM reduced neurite outgrowth and complexity with
reductions in various parameters of neurite outgrowth prevented when BV-2
microglia were pre-treated with either the IDO inhibitor, 1-methyltryptophan (1
MT) (L) (0.5mM; 30min), the KMO inhibitor, Ro 61-8048 (1MUM; 30min), the
synthetic glucocorticoid, dexamethasone (1MUM; 2h) -which suppresses IFNgamma
induced IDO - and the N-methyl-D-aspartate (NMDA) receptor antagonist, MK801
(0.1MUM; 30min). Overall this study indicates that inhibition of the KP in
microglia may be targeted to protect against reactive microglial-associated
neuronal atrophy.
PMID- 28688913
TI - Neuroprotective effect of Lovastatin on motor deficit induced by sciatic nerve
crush in the rat.
AB - Following severe peripheral nerve injury (PNI), regeneration is often
insufficient and functional recovery is incomplete. Any agents that limit the
spread of neural tissue damage may enhance the nerve regeneration. In this
regard, statins have been shown to have neuroprotective properties. We
investigated the effects of Lovastatin against sciatic nerve crush injury in male
Wistar Rats. Lovastatin or vehicle was given parenteraly to rats for 7 days
postoperative. In Lovastatin treatment groups, a single dose of agent (2 and
5mg/kg) was administered daily. The control group was given vehicle in the same
manner. The rats were subjected to crush injury in the left sciatic nerve with
non-serrated clamp for 30s. Behavioral, electrophysiological and morphological
alterations were evaluated during the experimental period. Results showed that
Lovastatin in a dose of 5mg/kg could significantly (P < 0.05) accelerate
regeneration process and functional recovery. Also results demonstrated that
morphometric parameters such as mean axonal number and myelin thickness were
significantly higher in Lovastatin (5mg/kg) treatment groups compared to controls
(P < 0.05). These findings suggest that a short-term course treatment with
Lovastatin can protect against sciatic nerve injury. Findings indicate that
postoperative administration of Lovastatin led to accelerate regeneration process
and motor function recovery in nerve crush model in rats. This effect might be
due to the anti-inflammatory, immunomodulatory or anti-oxidative properties of
Lovastatin. It is clear that more research is needed to confirm these findings.
PMID- 28688914
TI - Glucagon and glucagon-like peptide-1 as novel anti-inflammatory and
immunomodulatory compounds.
AB - Glucagon and glucagon-like peptide-1 (GLP-1) are polypeptide hormones that are
produced by pancreatic alpha-cells and the intestine, respectively, whose main
function is to control glucose homeostasis. The glucagon and GLP-1 levels are
imbalanced in diabetes. Furthermore, type 1 diabetic patients and animals present
with a diminished inflammatory response, which is related to some morbidities of
diabetes, such as a higher incidence of infectious diseases, including sepsis.
The focus of this review is to briefly summarize the state of the art concerning
the effects of glucagon and GLP-1 on the inflammatory response. Here, we propose
that glucagon and GLP-1 have anti-inflammatory properties, making them possible
prototypes for the design and synthesis of new compounds to treat inflammatory
diseases. In addition, glucagon, GLP-1 or their analogues or new derivatives may
not only be important for managing inflammatory diseases but may also have the
therapeutic potential to prevent, cure or ameliorate diabetes in patients by
counteracting the deleterious effects of pro-inflammatory cytokines on the
function and viability of pancreatic beta-cells. In addition, GLP-1, its
analogues or drugs that inhibit GLP-1 metabolism may have a doubly beneficial
effect in diabetic patients by inhibiting the inflammatory response and reducing
glycaemia.
PMID- 28688915
TI - Targeted proteome analysis with isotope-coded protein labels for monitoring the
influence of dietary phytochemicals on the expression of cytoprotective proteins
in primary human colon cells.
AB - : Cytoprotective effects by upregulating cellular expression levels of
antioxidant proteins are attributed to a significant number of food ingredients.
Evaluation of those cytoprotective effects and identification of the most active
components requires reliable and comprehensive proteomic strategies. Thus,
promising potential bioactive ingredients could be determined for the prevention
of various diseases, including colon cancer formation. We established a
multiplexed nanoLC-MS/MS targeted proteomic method, operated in scheduled
selected reaction monitoring mode (sSRM), to record modulation of the expression
levels of six major antioxidant proteins induced by dietary phytochemicals.
Relative quantification was achieved by isotope-coded protein labels (ICPLs) and
based on two to three proteotypic peptides per target protein. The assay provided
accurate (mean relative error 6.4%) and precise (mean RSD 7.4%) quantification.
Incubation experiments were carried out in primary human colon epithelial cells
(HCoEpiCs) and revealed significant upregulation of NAD(P)H dehydrogenase
[quinone] 1 (up to threefold) and thioredoxin reductase 1 (up to twofold) by
10MUM sulforaphane (from broccoli), 5MUM carnosol (rosemary), and 20MUM
cinnamaldehyde (cinnamon). The latter two substances additionally upregulated
heme oxygenase-1 and were identified as the most active components in the test
set. The results provide additional evidence for nutritive cytoprotection in
human colon cells. SIGNIFICANCE: Targeted proteome analysis using LC coupled to
scheduled selected reaction monitoring (sSRM)-MS is a highly flexible and
reliable method to monitor protein expression profiles. The present study
screened modulators occurring in food, which may be protective against colon
cancer by inducing cytoprotective enzymes. Primary human colonic epithelial cells
were used because they model the conditions in healthy gut tissue better than
immortalized cells. Thus, an LC-MS/MS-sSRM protocol was established and validated
including relative quantification of cytoprotective protein expression by isotope
coded protein labels, because metabolic labelling cannot be applied for primary
cells. The present study demonstrated that the major components of cinnamon and
rosemary, respectively, i.e. cinnamaldehyde and carnosol, are potent alimentary
candidates to increase the expression of cytoprotective enzymes in the human
colon. Among the investigated enzymes, NAD(P)H dehydrogenase [quinone] 1 (NQO1)
was most susceptible towards modulation by phytochemicals. NQO1 exerts its
cytoprotective activity by detoxifying electrophilic and oxidative xenobiotics
with quinone structure.
PMID- 28688916
TI - Venom proteome of the yellow-lipped sea krait, Laticauda colubrina from Bali:
Insights into subvenomic diversity, venom antigenicity and cross-neutralization
by antivenom.
AB - : The venom proteome of Laticauda colubrina (Bali, Indonesia) was elucidated by
nano-ESI-LCMS/MS of the venom reverse-phase HPLC fractions. Altogether 31
distinct forms of proteins were identified and clustered into three toxin
families: three-finger toxin (3FTX, 66.12% of total venom proteins),
phospholipase A2 (PLA2, 33.26%) and cysteine-rich secretory protein (CRiSP,
0.05%). The 3FTX were alpha-neurotoxins (five long neurotoxins, LNTX, 48.87%; two
short neurotoxins, SNTX, 16.94%) and a trace amount of two cytotoxins (CTX,
0.31%). PLA2 were present with a large diversity of homologues (>=20 forms),
however none was annotated to the lethal proteoform reported previously. The
venom is highly lethal in mice (LD50=0.10MUg/g) and this is driven primarily by
the SNTX and LNTX (LD50=0.05-0.13MUg/g), since the PLA2 proteins were non-lethal
up to 2MUg/g (20-time the venom LD50). The SNTX and LNTX were effectively cross
neutralized by the heterologous Sea Snake Antivenom (SSAV, Australian product)
(potency=0.27mg toxin per ml antivenom, and 0.40mg/ml, respectively),
corroborating the cross-neutralization of the whole venom (potency=1.09mg/ml) and
its antigenic immunoreactivity toward SSAV. Furthermore, compared with earlier
studies, the present work reveals geographical variation of venom composition for
L. colubrina which may have implication for the evolution and conservation of the
species. BIOLOGICAL SIGNIFICANCE: Laticauda colubrina (yellow-lipped sea krait)
is a widely distributed, semi-aquatic venomous snake species. The venom proteome
at the level of protein family is unsophisticated and consistent with its
restricted prey selection. Nonetheless, the subproteomic findings revealed
geographical variability of the venom for this widely distributed species. In
contrast to two previous reports, the results for the Balinese L. colubrina venom
showed that LNTX Neurotoxin a and Neurotoxin b were co-existent while the PLA2
lethal subtype (PLA-II) was undetected by means of LCMS/MS and by in vivo assay.
This is an observable trait of L. colubrina considered divergent from specimens
previously studied for the Philippines and the Solomon Islands. The stark
geographical variation might be reflective of trophic adaptation following
evolutionary arms race between the snake and the prey (eels) in different
localities. The preferred trait would likely propagate and remain significant
within the geographical population, since the strong behaviour of site fidelity
in the species would have minimized gene flow between distant populations.
Meanwhile, the in vivo neutralization study verified that the efficacy of the
heterologous Sea Snake Antivenom (Australian product) is attributable to the
cross-neutralization of SNTX and LNTX, two principal lethal toxins that made up
the bulk of L. colubrina venom proteins. The findings also implied that L.
colubrina, though could be evolutionarily more related to the terrestrial
elapids, has evolved a much streamlined, neurotoxin- and PLA2-predominated venom
arsenal, with major antigenicity shared among the true sea snakes and the
Australo-Papuan elapids. The findings enrich our current understanding of the
complexity of L. colubrina venom and the neutralizing spectrum of antivenom
against the principal toxins from this unique elapid lineage.
PMID- 28688917
TI - Real-World Economic Burden Associated with Transplantation-Related Complications.
AB - Approximately 20,000 hematopoietic cell transplantation (HCT) procedures are
performed annually in the United States. Real-world data on the costs associated
with post-transplantation complications are limited. Patients with hematologic
malignancies aged >=18 years undergoing autologous HCT (auto-HCT) or allogeneic
HCT (allo-HCT) between January 1, 2011, and June 30, 2014, were identified in the
Truven Health MarketScan Research Databases. Patients were required to have 12
months of continuous medical and pharmacy enrollment before and after HCT;
patients who experience inpatient death within 12 months post-HCT were also
included. Patients with previous HCT were excluded. Potential HCT-related
complications were identified if they had a medical claim with a diagnosis code
for relapse; infection; cardiovascular, renal, neurologic, pulmonary, hepatic, or
gastrointestinal disease; secondary malignancy; thrombotic microangiopathy; or
posterior reversible encephalopathy syndrome within 1 year post-HCT. Healthcare
costs attributable to these complications were evaluated by comparing total costs
in HCT recipients with complications and those without complications. The
MarketScan Research Databases were further linked to the Social Security
Administration's Master Death File to obtain patient death events in a subset of
patients. A total of 2672 HCT recipients were included in the analysis. The mean
+/- SD age of recipients was 54.5 +/- 11.6 years, and the majority of recipients
(63.6%) underwent auto-HCT. Complications were identified in 81% of auto-HCT
recipients and in 95.5% of allo-HCT recipients. Most complications occurred
within 180 days post-HCT. Compared with Auto-HCT recipients without
complications, those with complications incurred $51,475 higher adjusted total
costs (P < .01). Compared with allo-HCT recipients without complications, those
with complications incurred $181,473 higher adjusted total costs (P < .01). Among
the patients with mortality data, auto-HCT recipients with complications had a
higher mortality rate (13.4% vs 5.7%, P < .01) and a lower probability of
survival (P < .01) compared with those without complications. In allo-HCT
recipients, however, the mortality rate and probability of survival were not
significantly different between those with complications and those without
complications. HCT recipients with complications were associated with
considerable economic burden in terms of direct healthcare costs in a
commercially insured population, and in the case of auto-HCT, a higher mortality
rate was observed in those with complications.
PMID- 28688918
TI - Time-to-Event Ratio to Predict Outcome in Patients with Acute Myeloid Leukemia
Undergoing Allogeneic Hematopoietic Cell Transplantation?
PMID- 28688919
TI - Haploidentical Hematopoietic Cell Transplant with Post-Transplant
Cyclophosphamide and Peripheral Blood Stem Cell Grafts in Older Adults with Acute
Myeloid Leukemia or Myelodysplastic Syndrome.
AB - Many hematologic malignancies are diseases of aging, and the use of hematopoietic
cell transplant (HCT) is growing rapidly among older adults. Modern post
transplant cyclophosphamide (PTCy) protocols with haploidentical (haplo) donors
have dramatically expanded the donor pool for patients requiring HCT. Initial
studies were performed with bone marrow grafts, which require the donor to
undergo anesthesia during harvest. However, the use of mobilized peripheral blood
stem cells (PBSCs) may be desirable, especially with older donors. However, data
on PBSC haplo-HCT in older adults are lacking. To characterize the impact of age
on outcomes in haplo-HCT, we identified all adult patients undergoing haplo-HCT
with PTCy for acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) at
our institution from January 2009 to June 2016. Patients were grouped into 3
cohorts: Age 1 (<=55), Age 2 (55 to 65), and Age 3 (>=65). To characterize the
impact of donor type on outcomes in older patients, we identified age- and
disease risk index (DRI)-matched patient age >= 65 undergoing HLA-matched
unrelated donor (MUD) HCT for AML or MDS during the same time frame. Patients
were scored for disease risk and underlying comorbidities using the DRI and HCT
specific comorbidity index. Overall survival (OS) was analyzed using 3 different
Cox proportional hazards models. We identified 112 haplo-HCT patients, 95 with
AML and 17 with MDS. There were 61 patients in Age 1, 29 patients in Age 2, and
22 in Age 3. Median OS was 448, 397, and 147 days in Age 1, Age 2, and Age 3
patients (log-rank, P = .04). After adjusting for other risk factors, age >= 65
was associated with significantly worse OS after haplo-HCT (aHR, 2.16; 95% CI,
1.15 to 4.07). There was a trend toward increased relapse among older patients at
2 years (56%; 95% CI, 32% to 79%) versus Age 1 (41%; 95% CI, 28% to 54%) and Age
2 (31%; 95% CI, 12% to 50%) (P = .08). Among patients age >= 65, donor type (MUD
versus haplo) did not impact OS (aHR, 1.03; 95% CI, .56 to 1.88) after adjusting
for other risk factors. Prior allo-HCT (aHR, 4.95; 95% CI, 1.82 to 13.49) and
myeloablative conditioning (aHR, 1.97; 95% CI, 1.04 to 3.73) were associated with
inferior survival. Although age >= 65 was associated with inferior OS in our
haplo-HCT cohort, no difference was seen in survival between MUD and haplo-HCT.
Therefore, the use of haploidentical donors in older patients is a reasonable
treatment option, especially if there is concern for clinical deterioration. A
careful pretransplant evaluation and analysis of risks and benefits is warranted
when offering this transplant modality to older adults, especially in patients
with previous transplant or poor performance status. Strategies to reduce the
risk of relapse and decrease nonrelapse mortality in older adults are areas of
ongoing research, and prospective studies are needed.
PMID- 28688921
TI - Plasma Retinol Concentration Is Mainly Driven by Transthyretin in Hemodialysis
Patients.
AB - OBJECTIVE: Micronutrients deficiencies in hemodialysis patients are due to low
dietary intakes and intradialytic losses for hydrophilic micronutrients.
Conversely, lipophilic nondialyzable compounds might accumulate because of a lack
of elimination through renal metabolism or dialysis. Other compounds have complex
metabolism: their concentration is not explained by these phenomenons. The aim of
this study was to report plasma concentrations of lipophilic micronutrients in
hemodialysis patients and to analyze if these concentrations were predictive of
mortality. DESIGN: The design was monocentric observational longitudinal study.
SUBJECTS: A total of 123 hemodialysis patients included in this observational
study. MAIN OUTCOME MEASURE: Plasma concentration of lipophilic micronutrients
retinol and its two co-transporters transthyretin and retinol-binding protein 4,
tocopherol, and carotenoids (alpha-carotene and beta-carotene, beta
cryptoxanthin, lycopene, lutein, and zeaxanthin), and all factors associated with
1-year mortality. RESULTS: Within the 123 patients of the study, median age
(interquartile range) was 77.5 (69.5-84.5) years and 58.5% were male. Median
retinol plasma concentration was 4.07 (2.65-5.51) MUmol/L, and 91.9% of patient
had high plasma retinol concentrations. In monovariate analysis, retinol levels
were inversely correlated with mortality (hazard ratio = 0.57 [0.45-0.72]; P <
.001). This effect remained significant after adjustment with several parameters.
Nevertheless, the correlation between retinol and mortality disappeared as soon
as transthyretin was added in the statistical model, suggesting an effect of
transthyretin as confusing bias. Median tocopherol plasma concentration was 34.8
(28.3-42.9) MUmol/L and 72.4% of patients had high plasma tocopherol
concentration. Neither tocopherol plasma levels nor carotenoids concentrations
were correlated with death in multivariate analysis. CONCLUSIONS: In hemodialysis
patients, the correlation between retinol plasma concentration and mortality
represents the nutritional status but not a direct biological effect of retinol.
Retinol is only a surrogate predictor of mortality. It might not represent
vitamin A levels, but likely the transthyretin level. Plasma retinol levels
should be interpreted cautiously in hemodialysis patients.
PMID- 28688920
TI - Single-cell RNA sequencing reveals an altered gene expression pattern as a result
of CRISPR/cas9-mediated deletion of Gene 33/Mig6 and chronic exposure to
hexavalent chromium in human lung epithelial cells.
AB - Gene 33 (Mig6, ERRFI1) is an adaptor protein with multiple cellular functions. We
recently reported that depletion of this protein promotes lung epithelial cell
transformation induced by hexavalent chromium [Cr(VI)]. However, the early
molecular events that mediate this process are not clear. In the present study,
we used single-cell RNA sequencing to compare gene expression profiles between
BEAS-2B lung epithelial cells chronically exposed to a sublethal dose of Cr(VI)
with or without CRISPR/cas9-mediated deletion of Gene 33. Our data reveal 83
differentially expressed genes. The most notable changes are genes associated
with cell adhesion, oxidative stresses, protein ubiquitination, epithelial
mesenchymal transition/metastasis, and WNT signaling. Up-regulation of some neuro
specific genes is also evident, particularly ubiquitin carboxyl-terminal
hydrolase L1 (UCHL1), a deubiquitinase and potential biomarker for lung cancer.
Gene 33 deletion and/or Cr(VI) exposure did not cause discernable changes in cell
morphology. However, Gene 33 deletion led to a modest but significant reduction
of cells in the G2/M phase of the cell cycle regardless of Cr(VI) exposure. Gene
33 deletion also significantly reduced cell proliferation. Interestingly, Cr(VI)
exposure eliminated the difference in cell proliferation between the two
genotypes. Gene 33 deletion also significantly elevated cell migration. Our data
indicate that combined Gene 33 deletion and chronic Cr(VI) exposure produces a
gene expression pattern and a phenotype resemble those of the transformed lung
epithelial cells. Given the known association of UCHL1 with lung cancer, we
propose that UCHL1 is an important player in the early stage of lung epithelial
cell transformation and tumorigenesis.
PMID- 28688922
TI - Use of family relationships improved consistency of identification of Aboriginal
people in linked administrative data.
AB - BACKGROUND AND OBJECTIVES: Algorithms are often used to improve identification of
Aboriginal Australians in linked data sets with inconsistent and incomplete
recording of Aboriginal status. We compared how consistently some common
algorithms identified family members, developed a new algorithm incorporating
relatives' information, and assessed the effects of these algorithms on health
estimates. METHODS: The sample was people born 1980-2011 recorded as Aboriginal
at least once (or a relative) in four Western Australian data sets and their
relatives (N = 156,407). A very inclusive approach, ever-Aboriginal (EA/EA+,
where + denotes children's records incorporated), and two more specific
approaches, multistage median (MSM/MSM+) and last record (LR/LR+), were chosen,
along with the new algorithm (MSM+Family). RESULTS: Ever-Aboriginal (EA)
categorized relatives the least consistently; 25% of parent-child triads had
incongruent Aboriginal statuses with EA+, compared with only 9% with MSM+. With
EA+, 14% of full siblings had different statuses compared with 8% for MSM+. EA
produced the lowest estimates of the proportion of Aboriginal people with poor
health outcomes. Using relatives' records reduced the number of uncategorized
people and categorized as Aboriginal more people who had few records (e.g., no
hospital admissions). CONCLUSION: When many data sets are linked, more specific
algorithms select more representative Aboriginal samples and identify
Aboriginality of relatives more consistently.
PMID- 28688923
TI - Paraoxonase activities in human follicular fluid: role in follicular maturation.
AB - The paraoxonases (PONs) are antioxidant enzymes associated with beneficial
effects against several diseases and some exposures. Little is known, however,
about the role of PONs in human reproduction. This work was conducted to
investigate whether any association existed between the activities of the PON
enzymes (1, 2, and 3) with the follicular size and fertility parameters in
assisted reproduction. The study included 100 subfertile women (patients) and 55
proven fertile women (oocyte donors), all undergoing an ovarian stimulation
cycle. Follicular fluid from small (diameter <12 mm) and large (diameter >=18 mm)
follicles was collected from each woman. The PONs were quantified in follicular
fluid by immunoblotting. PON1 arylesterase and paraoxonase, PON2 methyl
paraoxonase and PON3 simvastatinase activities from both donors and patients were
significantly higher (P < 0.001) in follicular fluid from large follicles
compared with small ones. In large follicles, PON3 activity was significantly
higher (P < 0.01) in donors compared with patients. Follicular fluid PON1
arylesterase and paraoxonase activity was positively correlated with the number
of retrieved oocytes in donors. This study shows an increase in the activities of
PONs with follicle size, thus providing indirect evidence for the role of PONs in
follicle maturation.
PMID- 28688924
TI - Healthy preconception nutrition and lifestyle using personalized mobile health
coaching is associated with enhanced pregnancy chance.
AB - Periconceptional nutrition and lifestyle are essential in pathogenesis and
prevention of most reproductive failures, pregnancy outcome and future health. We
aimed to investigate whether personalized mobile health (mHealth) coaching
empowers couples contemplating pregnancy to increase healthy behaviour and
chances of pregnancy. A survey was conducted among 1053 women and 332 male
partners who received individual coaching using the mHealth programme 'Smarter
Pregnancy' to change poor nutrition and lifestyle for 26 weeks, depending on
pregnancy state and gender. Poor behaviours were translated into a total risk
score (TRS) and Poisson regression analysis was performed to estimate
associations with the chance of pregnancy adjusted for fertility status, age and
baseline body mass index expressed as adjusted hazard ratio (aHR) and 95%
confidence interval (95% CI). A lower (a)HR suggests a higher chance of achieving
pregnancy. A higher TRS was significantly associated with a lower chance of
pregnancy in all women (aHR 0.79, 95% CI 0.72-0.85) and (a)HR was lowest in women
whose male partner participated (aHR 0.75, 95% CI 0.61-0.91). This survey shows
that empowerment of couples in changing poor nutrition and lifestyle using
personalized mHealth coaching is associated with an enhanced pregnancy chance in
both infertile and fertile couples.
PMID- 28688925
TI - Stable isotope analyses of precipitation nitrogen sources in Guiyang,
southwestern China.
AB - To constrain sources of anthropogenic nitrogen (N) deposition is critical for
effective reduction of reactive N emissions and better evaluation of N deposition
effects. This study measured delta15N signatures of nitrate (NO3-), ammonium
(NH4+) and total dissolved N (TDN) in precipitation at Guiyang, southwestern
China and estimated contributions of dominant N sources using a Bayesian isotope
mixing model. For NO3-, the contribution of non-fossil N oxides (NOx, mainly from
biomass burning (24 +/- 12%) and microbial N cycle (26 +/- 5%)) equals that of
fossil NOx, to which vehicle exhausts (31 +/- 19%) contributed more than coal
combustion (19 +/- 9%). For NH4+, ammonia (NH3) from volatilization sources
(mainly animal wastes (22 +/- 12%) and fertilizers (22 +/- 10%)) contributed less
than NH3 from combustion sources (mainly biomass burning (17 +/- 8%), vehicle
exhausts (19 +/- 11%) and coal combustions (19 +/- 12%)). Dissolved organic N
(DON) accounted for 41% in precipitation TDN deposition during the study period.
Precipitation DON had higher delta15N values in cooler months (13.10/00) than in
warmer months (-7.00/00), indicating the dominance of primary and secondary ON
sources, respectively. These results newly underscored the importance of non
fossil NOx, fossil NH3 and organic N in precipitation N inputs of urban
environments.
PMID- 28688926
TI - Microbes from mined sites: Harnessing their potential for reclamation of derelict
mine sites.
AB - Derelict mines pose potential risks to environmental health. Several factors such
as soil structure, organic matter, and nutrient content are the greatly affected
qualities in mined soils. Soil microbial communities are an important element for
successful reclamation because of their major role in nutrient cycling, plant
establishment, geochemical transformations, and soil formation. Yet,
microorganisms generally remain an undervalued asset in mined sites. The
microbial diversity in derelict mine sites consists of diverse species belonging
to four key phyla: Proteobacteria, Acidobacteria, Firmicutes, and Bacteroidetes.
The activity of plant symbiotic microorganisms including root-colonizing
rhizobacteria and ectomycorrhizal fungi of existing vegetation in the mined sites
is very high since most of these microbes are extremophiles. This review outlines
the importance of microorganisms to soil health and the rehabilitation of
derelict mines and how microbial activity and diversity can be exploited to
better plan the soil rehabilitation. Besides highlighting the major breakthroughs
in the application of microorganisms for mined site reclamation, we provide a
critical view on plant-microbiome interactions to improve revegetation at the
mined sites. Also, the need has been emphasized for deciphering the molecular
mechanisms of adaptation and resistance of rhizosphere and non-rhizosphere
microbes in abandoned mine sites, understanding their role in remediation, and
subsequent harnessing of their potential to pave the way in future rehabilitation
strategies for mined sites.
PMID- 28688927
TI - An unexpected friend - ROS in apoptosis-induced compensatory proliferation:
Implications for regeneration and cancer.
AB - Apoptosis-induced compensatory proliferation (AiP) is a form of compensatory
proliferation that is triggered by apoptotic cell death to maintain tissue
homeostasis. As such, AiP is essential for many tissue repair processes including
regeneration. The apoptotic effectors, termed caspases, not only execute
apoptosis, but are also directly involved in the generation of the signals
required for AiP. Reactive oxygen species (ROS) play an important role for
regenerative processes. Recently, it was shown in Drosophila that apoptotic
caspases can mediate the generation of ROS for promoting AiP. This review
summarizes and discusses these findings in the context of regenerative processes
and cancer.
PMID- 28688929
TI - Plant glyco-biotechnology.
AB - Glycosylation is an important protein modification in all eukaryotes. Whereas the
early asparagine-linked glycosylation (N-glycosylation) and N-glycan processing
steps in the endoplasmic reticulum are conserved between mammals and plants, the
maturation of complex N-glycans in the Golgi apparatus differs considerably. Due
to a restricted number of Golgi-resident N-glycan processing enzymes and the
absence of nucleotide sugars such as CMP-N-acetylneuraminic acid, plants produce
only a limited repertoire of different N-glycan structures. Moreover, mammalian
mucin-type O-glycosylation of serine or threonine residues has not been described
in plants and the required machinery is not encoded in their genome which enables
de novo build-up of the pathway. As a consequence, plants are very well-suited
for the production of homogenous N- and O-glycans and are increasingly used for
the production of recombinant glycoproteins with custom-made glycans that may
result in the generation of biopharmaceuticals with improved therapeutic
potential.
PMID- 28688928
TI - Transport from the endoplasmic reticulum to the Golgi in plants: Where are we
now?
AB - The biogenesis of about one third of the cellular proteome is initiated in the
endoplasmic reticulum (ER), which exports proteins to the Golgi apparatus for
sorting to their final destination. Notwithstanding the close proximity of the ER
with other secretory membranes (e.g., endosomes, plasma membrane), the ER is also
important for the homeostasis of non-secretory organelles such as mitochondria,
peroxisomes, and chloroplasts. While how the plant ER interacts with most of the
non-secretory membranes is largely unknown, the knowledge on the mechanisms for
ER-to-Golgi transport is relatively more advanced. Indeed, over the last fifteen
years or so, a large number of exciting results have contributed to draw
parallels with non-plant species but also to highlight the complexity of the
plant ER-Golgi interface, which bears unique features. This review reports and
discusses results on plant ER-to-Golgi traffic, focusing mainly on research on
COPII-mediated transport in the model species Arabidopsis thaliana.
PMID- 28688930
TI - Probing the unseen structure and function of liver cells through atomic force
microscopy.
AB - With the arrival of atomic force microscopy (AFM) about thirty years ago, this
new imaging tool opened up a new area for the exploration of biological samples,
ranging from the tissue and cellular level down to the supramolecular scale.
Commercial instruments of this new imaging technique began to appear in the five
years following its discovery in 1986 by Binnig, Quate & Gerber. From that point
onwards the AFM has attracted many liver biologists, and the number of
publications describing structure-function relationships on the diverse set of
liver cells has grown steadily ever since. It is therefore timely to reflect on
the achievements of AFM in disclosing the cellular architecture of hepatocytes,
liver sinusoidal endothelial cells, Kupffer cells, stellate cells and liver
associated natural killer cells. In this thematic paper, we present new data and
provide an in-depth overview of the current AFM literature on liver cell biology.
We furthermore include a future outlook on how this scanning probe imaging tool
and its latest developments can contribute to clarify various structural and
functional aspects of cells in liver health and disease.
PMID- 28688931
TI - Membrane engineering - A novel strategy to enhance the production and
accumulation of beta-carotene in Escherichia coli.
AB - Carotenoids are a class of terpenes of commercial interest that exert important
biological functions. While various strategies have been applied to engineer beta
carotene production in microbial cell factories, no work has been done to study
and improve the storage of hydrophobic terpene products inside the heterologous
host cells. Although the membrane is thought to be the cell compartment that
accumulates hydrophobic terpenes such as beta-carotene, direct evidence is still
lacking. In this work, we engineered the membrane of Escherichia coli in both its
morphological and biosynthetic aspects, as a means to study and improve its
storage capacity for beta-carotene. Engineering the membrane morphology by
overexpressing membrane-bending proteins resulted in a 28% increase of beta
carotene specific producton value, while engineering the membrane synthesis
pathway led to a 43% increase. Moreover, the combination of these two strategies
had a synergistic effect, which caused a 2.9-fold increase of beta-carotene
specific production value (from 6.7 to 19.6mg/g DCW). Inward membrane stacks were
observed in electron microscopy images of the engineered E. coli cells, which
indicated that morphological changes were associated with the increased beta
carotene storage capacity. Finally, membrane separation and analysis confirmed
that the increased beta-carotene was mainly accumulated within the cell membrane.
This membrane engineering strategy was also applied to the beta-carotene
hyperproducing strain CAR025, which led to a 39% increase of the already high
beta-carotene specific production value (from 31.8 to 44.2mg/g DCW in shake
flasks), resulting in one of the highest reported specific production values
under comparable culture conditions. The membrane engineering strategy developed
in this work opens up a new direction for engineering and improving microbial
terpene producers. It is quite possible that a wide range of strains used to
produce hydrophobic compounds can be further improved using this novel
engineering strategy.
PMID- 28688932
TI - Neurologic complications of shoulder joint replacement.
AB - BACKGROUND: Little attention has been given to neurologic complications after
shoulder joint replacement (SJR). Previously thought to occur infrequently, it is
likely that many are not clinically recognized, and they can result in
postoperative morbidity and impair the patient's recovery. The purpose of this
study was to document the prevalence of nerve complications after SJR, to
identify the nerves involved, and to define patient outcomes. METHODS: This was a
retrospective review of 211 SJRs in 202 patients during a 5-year period were
included, with 89 male and 122 female patients at an average age of 70 years. All
patients underwent a comprehensive analysis of any postoperative nerve
complication, including onset, duration, investigation, treatment, and symptom
resolution. RESULTS: Of the 211 SJR procedures, 44 were identified as having
sustained a nerve complication (20.9%), with 36 female (81.8%) and 8 male
patients (18.2%). Reverse SJR was associated with the highest number of nerve
complications. The median nerve (25 patients) and musculocutaneous nerve (8
patients) were most commonly involved. Most nerve complications were transient
and resolved within 6 months. Permanent sequelae and injuries that required
secondary surgical intervention were rare. CONCLUSION: The occurrence of nerve
complications after SJR is common, but almost all will fully recover. Most are
transient neurapraxias involving the lateral cord of the brachial plexus. Women
are more likely to be affected, as are patients who have undergone prior surgery
to the affected shoulder. Most are likely to be the result of excessive traction
or direct injury to the nerves during glenoid exposure.
PMID- 28688933
TI - Defining optimal calcar screw positioning in proximal humerus fracture fixation.
AB - BACKGROUND: Anatomic reduction and placement of an inferior calcar screw are
strategies to prevent fixation failure in proximal humerus factures. Optimal
position of the calcar screw remains unknown. METHODS: There were 168 shoulders
(68.5% female; average age, 63.6 +/- 11.5 years) that underwent open reduction
and internal fixation of a displaced proximal humerus fracture involving the
surgical or anatomic neck. Univariate and multivariate analyses were performed on
preoperative clinical, preoperative radiographic, and postoperative radiographic
variables to determine association with fixation failure. A receiver operating
characteristic curve was performed to determine a maximum distance from the
inferior screw to the calcar ("calcar distance") as well as a maximum ratio of
this distance and the head diameter ("calcar ratio"). RESULTS: There were 26 of
168 (15.5%) patients with radiographic failures (19 related to fixation failure).
Univariate analysis and multivariate analyses found quality of reduction (P <
.001), calcar distance (P < .001), and calcar ratio (P < .001) to be
significantly associated with radiographic success. In all patients, receiver
operating characteristic analysis found quantifiable thresholds of 12 mm or
within the bottom 25% of the humeral head as measures to prevent fixation
failure. CONCLUSIONS: Quality of reduction, calcar distance, and calcar ratio
independently correlated with fixation failure. This study provides optimal
distances and ratios for calcar screw placement that can be used clinically.
PMID- 28688934
TI - Humeral bone resorption after anatomic shoulder arthroplasty using an uncemented
stem.
AB - BACKGROUND: Bone resorption around the femoral stem after total hip arthroplasty
is a well-known phenomenon. However, only a few studies have evaluated bone
resorption after shoulder arthroplasty. This study investigated the prevalence of
humeral bone resorption after different shoulder arthroplasty procedures.
METHODS: The study included 147 shoulders that underwent total shoulder
arthroplasty (TSA) or humeral head replacement (HHR) with an uncemented humeral
stem from November 2008 to May 2015 and were monitored for more than 1 year. The
prevalence of humeral bone resorption and risk factors were investigated.
RESULTS: The most advanced grade of bone resorption, grade 0, occurred in 21
shoulders (14.3%). Grade 1 bone resorption occurred in 10 (6.8%), grade 2 in 28
(19.0%), grade 3 in 61 (41.5%), and grade 4 in 27 (18.4%). High occurrence of
bone absorption was observed in zones 1, 2, and 7. Grade 4 bone resorption did
not occur in zones 3 and 5. HHR, on-growth type stem coating, and occupation
ratio were significant independent risk factors for grade >=3 bone resorption,
whereas female sex and HHR were significant independent risk factors for grade 4.
CONCLUSION: Bone resorption was observed in 126 shoulders (85.7%), and full
thickness cortical bone resorption occurred in 27 shoulders (18.4%). Bone
resorption was frequently observed at the greater tuberosity, lateral diaphysis,
and calcar region (zones 1, 2, and 7). Significant risk factors included female
sex, HHR with rotator cuff reconstruction, on-growth type stem coating, and high
occupation ratio of the implant.
PMID- 28688935
TI - Indirect transfer of the sternal head of the pectoralis major with autogenous
semitendinosus augmentation to treat scapular winging secondary to long thoracic
nerve palsy.
AB - BACKGROUND: Scapular winging resulting from long thoracic nerve palsy is uncommon
but debilitating, and the choice of surgical treatment is inconsistent. The
autogenous semitendinosus tendon plays a key role as an interposed tendon graft,
although its use in the indirect transfer of the sternal head of the pectoralis
major during the treatment of scapular winging has rarely been reported.
MATERIALS AND METHODS: A retrospective review was performed during a 9-year
period from the clinical data of 26 cases (28 shoulders) with indirect transfer
of the sternal head of the pectoralis major with the interposition of an
autogenous semitendinosus tendon graft for dynamic stabilization of the scapula.
The range of active movement (forward elevation, abduction, and external
rotation), American Shoulder and Elbow Surgeons score, visual analog scale score,
and complications were evaluated with a mean of 47 months of clinical follow-up.
RESULTS: Patients' active shoulder movements (forward elevation, abduction, and
external rotation), American Shoulder and Elbow Surgeons score, and visual analog
scale score showed significant improvements (P < .01). One seroma developed and
resolved with extraction. Four shoulders had adhesive capsulitis and recovered
after physiotherapy. There was no recurrence of scapular winging in any patient.
CONCLUSION: Timely treatment, often surgical, is vital to the recovery of
scapular winging secondary to long thoracic nerve palsy. Our results suggest that
indirect transfer of the sternal head of the pectoralis major with interposition
of the autogenous semitendinosus tendon can effectively treat scapular winging
due to long thoracic nerve palsy with limited sequelae. Widespread use of this
technique is recommended.
PMID- 28688936
TI - Open versus arthroscopic surgical treatment for anterior shoulder dislocation: a
comparative systematic review and meta-analysis over the past 20 years.
AB - BACKGROUND: The purpose of this study was to perform a meta-analysis comparing
open and arthroscopic surgery for the treatment of anterior shoulder instability
by analyzing comparative studies during 2 different time intervals during the
last 20 years. METHODS: We conducted a systematic review of MEDLINE, Embase,
Scopus, and Google Scholar. Two groups were created by dividing studies according
to the year of publication, those published from 1995 to 2004 or from 2005 to
2015. Publication bias and risk of bias were assessed using the Cochrane
Collaboration's tools. Heterogeneity was assessed using the I2 statistics.
RESULTS: A total of 22 studies (n = 1633) met the eligibility criteria.
Comparison of the pooled estimate for all of these studies demonstrated no
significant differences (P = .64) in clinical outcomes between open and
arthroscopic shoulder stabilization. However, studies published from 1995 through
2004 demonstrated significant differences (P = .015) in recurrence rates favoring
open surgery. In contrast, no significant differences (P = .09) in recurrence
rates were observed for studies published from 2005 through 2015. The pooled
estimate for all studies in both groups demonstrated significant differences (P =
.001) in external rotation deficits between open and arthroscopic shoulder
stabilization favoring arthroscopic surgery. CONCLUSION: Despite advances in
surgical techniques and devices during the last 20 years, either open or
arthroscopic surgical treatment of anterior shoulder dislocation results in
similar clinical outcomes. The recurrence rate for arthroscopic surgical
stabilization has only marginally decreased, from 16.8% to 14.2%. However, during
the earlier decade from 1995 through 2004, patients treated with arthroscopic
surgery had twice the risk of recurrence compared with an open procedure.
PMID- 28688937
TI - Acromioplasty in patients selected for operation by national guidelines.
AB - BACKGROUND: Shoulder impingement syndrome is the most common shoulder disorder.
Even though conservative treatment is the primary treatment of choice, surgery
has increased substantially in several countries during the last 20 years. This
has resulted in recommended clinical guidelines for treatment of shoulder
impingement syndrome in countries such as The Netherlands and Denmark during
recent years. The aim of this study was to investigate the effectiveness of an
arthroscopic subacromial decompression in 244 patients selected for surgery
according to national clinical guidelines. MATERIALS AND METHODS: Patients were
included from an Internet-based shoulder and elbow database. They were asked to
complete 2 questionnaires consisting of the Oxford Shoulder Score (OSS) and the
EuroQol 5-Dimension 3-Level and visual analog scale preoperatively and at 6-month
follow-up. All patients were carefully selected for surgery according to the
national guidelines, with symptoms persisting for at least 6 months. Furthermore,
subgroups related to the OSS were formed to assess the clinical outcome according
to preoperative status and age. RESULTS: For the complete study group, an OSS
change of 10 (8.8-11.2; P = .0001) was found at 6-month follow-up. No significant
difference was found between the genders (P = .17). The largest clinical effect
from the intervention was found in the low preoperative OSS (pre-OSS) group, in
which a mean change of 17 was found. The moderate and high pre-OSS groups had
mean changes of 13 and 5, respectively. Similarly, according to the EuroQol 5
Dimension 3-Level and visual analog scale, the largest improvements were seen in
the low and moderate pre-OSS groups. CONCLUSION: Arthroscopic subacromial
decompression is a valid treatment, reducing pain and improving quality of life
for patients selected for surgery according to the Danish national guidelines.
PMID- 28688938
TI - Comparative study of endoscopic surveillance in hereditary diffuse gastric cancer
according to CDH1 mutation status.
AB - BACKGROUND AND AIMS: Hereditary diffuse gastric cancer (HDGC) accounts for 1% of
gastric cancer cases. For patients with a germline CDH1 mutation, risk-reducing
gastrectomy is recommended. However, for those delaying surgery or for families
with no causative mutation identified, regular endoscopy is advised. This study
aimed to determine the yield of signet ring cell carcinoma (SRCC) foci in
individuals with a CDH1 pathogenic variant compared with those without and how
this varies with successive endoscopies. METHODS: Patients fulfilling HDGC
criteria were recruited to a prospective longitudinal cohort study. Endoscopy was
performed according to a strict protocol with visual inspection followed by focal
lesion and random biopsy sampling to detect foci of SRCC. Survival analysis
determined progression to finding of SRCC according to CDH1 mutation status. The
European Organization for Research and Treatment of Cancer Quality of Life
Questionnaire Core 30 and 36-item Short Form Health Survey questionnaires
assessed quality of life before surveillance and each endoscopy. RESULTS: Eighty
five individuals fulfilling HDGC criteria underwent 201 endoscopies; 54 (63.5%)
tested positive for CDH1 mutation. SRCC yield was 61.1% in CDH1 mutation carriers
compared with 9.7% in noncarriers, and mutation-positive patients had a 10-fold
risk of SRCC on endoscopy compared with those with no mutation detected (P <
.0005). Yield of SRCC decreased substantially with subsequent endoscopies.
Surveillance was associated with improved psychological health. CONCLUSIONS: SRCC
foci are prevalent in CDH1 mutation carriers and can be detected at endoscopy
using a standardized, multiple biopsy sampling protocol. Decreasing yield over
time suggests that the frequency of endoscopy might be reduced. For patients with
no CDH1 pathogenic variant detected, the cost-to-benefit ratio needs to be
assessed in view of the low yield.
PMID- 28688939
TI - Mapping Geospatial Gaps in Early Identification of Children With Autism Spectrum
Disorder.
AB - Despite the known developmental benefits of early intervention for autism
spectrum disorder (ASD), diagnosis before age 5 years is often not achieved.
Research suggests that lack of health insurance and living in rural areas and
areas of severe provider shortages contribute significantly to these delays. The
purpose of this project was to conduct a geospatial evaluation of potential gaps
in early ASD diagnosis of uninsured children in Virginia. A secondary purpose was
to show the use of geospatial analysis by pediatric nurse practitioners for
policy advocacy. We mapped data from a statewide provider of ASD evaluative
services associated with the Virginia Department of Health and found several
communities with high numbers of uninsured children where children may not be
receiving early diagnostic services. Pediatric nurse practitioners can help
address community-level gaps in early identification of ASD for uninsured young
children living in rural areas by conducting outreach programs to providers and
families within rural communities and concurrently partnering with nurse
scientists to develop visually impactful geospatial analyses to educate
legislators and further advocate for policy positions.
PMID- 28688940
TI - Thoracostomy Tube Removal: Implementation of a Multidisciplinary Procedural Pain
Management Guideline.
AB - OBJECTIVE: Thoracostomy tubes are placed following cardiothoracic surgery for the
repair or palliation of congenital heart defects. The aim of this project was to
develop and implement a clinical practice guideline for the provision of optimal
analgesia during removal of thoracostomy tubes in pediatric postoperative
cardiothoracic surgery patients. METHODS: Methods used include a nonexperimental
design utilizing chart audits to determine baseline documentation as well as
procedure note evaluation to determine both baseline documentation and compliance
with the new guideline. A convenience sample of unit-based nurses completed a
knowledge test and a post-implementation survey. RESULTS: There was a significant
increase in nursing knowledge related to the clinical practice guideline
education and implementation. Documentation compliance was observed. Nursing
satisfaction and feasibility of the new guideline was demonstrated. DISCUSSION:
This project was successful in increasing nursing knowledge of available
resources for optimal procedural pain management in pediatric patients requiring
thoracostomy tube removal on one in-patient acute care unit.
PMID- 28688941
TI - Sodium thiosulfate post-conditioning protects rat hearts against ischemia
reperfusion injury via reduction of apoptosis and oxidative stress.
AB - Pharmacological agents given at the time of reperfusion can protect the heart
from ischemia reperfusion injury (IR). Being a calcium chelator, antioxidant and
mitochondrial potassium channel modulator, sodium thiosulfate (STS) was chosen to
treat myocardial IR injury. Isolated rat heart model was used to induce IR injury
and the hemodynamic changes were monitored using PowerLab (AD Instruments,
Australia). STS at a dose of 1 mM given at the early stage of reperfusion
significantly reduced the infarct size and recovered the failing heart from
reperfusion injury. Its action was based on reduction of apoptosis as evidenced
from decreased activity of caspase-3 in the myocardium, lowered expression of
casp-3 and PARP, which was supported by absence of significant DNA fragmentation
and histological derangement of fibers compared to the injury control. An
evaluation of the inter-dependency of H2S and STS biosynthesis in the STS treated
groups showed no significant changes in the level of STS, H2S and rhodanese,
except the cystathionine gamma lyase activity that improved upon treatment. The
mechanism underlying the antiapoptotic, mitochondrial preservation and
antioxidant effects of STS were related to the biosynthesis of H2S. The fact that
inhibition of cystathionine gamma lyase limited the STS mediated cardio
protection supports this observation.
PMID- 28688942
TI - Wogonin, a natural flavonoid, intercalates with genomic DNA and exhibits
protective effects in IL-1beta stimulated osteoarthritis chondrocytes.
AB - Wogonin has recently been shown to possess anti-inflammatory and
chondroprotective properties and is of considerable interest due to its broad
pharmacological activities. The present study highlights that Wogonin binds DNA
and exerts chondroprotective effects in vitro. Wogonin showed strong binding with
chondrocytes genomic DNA in vitro. The mode of binding of Wogonin to genomic-DNA
was assessed by competing Wogonin with EtBr or DAPI, known DNA intercalator and a
minor groove binder, respectively. EtBr fluorescence reduced significantly with
increase in Wogonin concentration suggesting possible DNA intercalation of
Wogonin. Further, in silico molecular docking of Wogonin on mammalian DNA also
indicated possible intercalation of Wogonin with DNA. The denaturation and FRET
studies revealed that Wogonin prevents denaturation of DNA strands and provide
stability to genomic DNA against a variety of chemical denaturants. The cellular
uptake study showed that Wogonin enters osteoarthritis chondrocytes and was
mainly localized in the nucleus. Wogonin treatment to OA chondrocytes protects
the fragmentation of genomic DNA in response to IL-1beta as evaluated by DNA
ladder and TUNEL assay. Treatment of chondrocytes with Wogonin resulted in
significant suppression of IL-1beta-mediated induction of ROS. Further, Wogonin
exhibited protective potential through potent suppression of extrinsic and
intrinsic apoptotic pathways and induction of anti-apoptotic proteins in IL-1beta
stimulated osteoarthritis chondrocytes. Our data thus suggest that DNA
intercalation by Wogonin may result in the stabilization of genomic DNA leading
to protective activity.
PMID- 28688943
TI - Antioxidative, anti-inflammation and lung-protective effects of mycelia selenium
polysaccharides from Oudemansiella radicata.
AB - The present work was designed to investigated the antioxidant, anti-inflammation,
and pulmonary protective effects of SMPS and MPS from Oudemansiella radicata on
LPS-induced lung injured mice. The results demonstrated that SMPS showed
potential effects on relieving lung injury and preventing oxidative stress,
reflecting by decreasing the serum levels of C3, CRP and GGT, increasing the
pulmonary activities of SOD, GSH-Px, CAT and T-AOC, as well as down-regulating
the MDA and LPO contents, respectively. Furthermore, the levels of TNF-alpha
(224.211+/-3.12ng/mL), IL-1beta (254.557+/-2.18ng/L), and IL-6 (18.214+/
0.15ng/L) in BALF of mice treated with SMPS at the dosage of 400mg/kg/d
significantly lower than that in the lung injured mice. These conclusions
indicated that both SMPS and MPS possessed potent antioxidants and anti
inflammation activities, and could be used as functional foods and natural drugs
in preventing lung injury.
PMID- 28688944
TI - Enhancement of extracellular polymeric substances (EPS) production in Spirulina
(Arthrospira sp.) by two-step cultivation process and partial characterization of
their polysaccharidic moiety.
AB - The interactive effects of light intensity and NaCl concentration were
investigated for Spirulina two-step cultivation process using Full Factorial
Design. In the experiment interval, light intensity had no effect while the NaCl
concentration had significant effect on the enhancement of extracellular
polymeric substances (EPS) production. Interestingly, results revealed a
significant negative interaction between light and NaCl concentration indicating
that high NaCl concentration (40gL-1) and low light intensity (10MUmol photons m
2s-1) enhanced the EPS production. Under these conditions, EPS production reached
a maximum of 1.02gg-1 of biomass (dry weight), which is 1.67-folds greater than
EPS content under optimal growth conditions (10MUmol photons m-2s-1, 1gL-1, 30
degrees C). Desalting and deproteinezation steps of EPS were efficient to obtain
polysaccharides (PS) with high carbohydrate (67.3+/-1.1%), low soluble proteins
(5.14+/-0.32%), ash (5.85+/-0.71%) and sulfate (2.42+/-0.12%) contents.
Rheological studies of PS at different concentrations (1%, 2.5% and 5%) revealed
that the viscosity of the solution increased with the increase of PS
concentration. In addition, PS exhibited a non Newtonian shear-thinning nature, a
predominant gel-like behavior and a good resistance to consecutive heating
cooling cycles. The adopted process could be, then, a promising and economic
strategy to enhance EPS production and extract polysaccharides with interesting
rheological properties.
PMID- 28688945
TI - Purification and structural characterization of a novel anti-tumor protein from
Arca inflata.
AB - A novel in vitro anti-tumor protein (J2-C2) with a molecular weight of 27,153.0Da
was isolated from the edible portion of Arca inflata. Physical and structural
properties of J2-C2 were characterized using physicochemical and instrumental
analyses. Gel electrophoresis analysis showed that J2-C2 is a homogeneous,
monomeric protein with an isoelectric point of 6.3. The purity of the isolated
native J2-C2 was >99%, as determined by RP-HPLC. The carbohydrate content assay
showed that J2-C2 was not a glycoprotein. The FT-IR spectrum of J2-C2 gave
characteristic amide absorption bands at 1645.71 and 1541.46cm-1. Secondary
structure analysis by CD spectroscopy revealed that J2-C2 had 34.0% alpha-helix,
27.5% beta-sheet, 13.4% beta-turn and 25.1% random coil. In-gel and nano ESI
MS/MS sequencing analysis combined with transcriptome unigene analysis yielded
the complete amino acid sequence of J2-C2. Aligning with NCBI BLAST database, J2
C2 showed 77% homology with predicted triosephosphate isomerase (TIM) derived
from Crassostrea gigas. Therefore, J2-C2 was considered to be a new TIM-like
protein in A. inflata. The anti-tumor effect of J2-C2 against three human tumor
cells was measured by MTT assay, and the IC50 values of J2-C2 were 42.38, 45.64
and 48.73MUM against A549, HepG2 and SPC-A-1 cell lines, respectively.
PMID- 28688946
TI - WITHDRAWN: Anti-arthritic effect of pilose antler peptide on adjuvant-induced
rheumatoid arthritis in rats.
AB - This article has been withdrawn at the request of the author(s) and/or editor.
The Publisher apologizes for any inconvenience this may cause. The full Elsevier
Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our
business/policies/article-withdrawal.
PMID- 28688947
TI - Estimation of thermodynamic stability of human carbonic anhydrase IX from urea
induced denaturation and MD simulation studies.
AB - Carbonic anhydrase IX (CAIX) is a transmembrane glycoprotein, overexpressed in
cancer cells under hypoxia condition. In cancerous cells, CAIX plays an important
role to combat the deleterious effects of a high rate of glycolytic metabolism.
In order to favor tumor survival, CAIX maintains intracellular pH neutral or
slightly alkaline and extracellular acidic pH. The equilibrium unfolding and
conformational stability of CAIX were measured in the presence of increasing urea
concentrations to understand it's structural features under stressed conditions.
Two different spectroscopic techniques were used to follow urea-induced
denaturation and observed that urea induces a reversible denaturation of CAIX.
Coincidence of the normalized transition curves of both optical properties
suggesting that denaturation of CAIX is a two-state process, i.e., native state <
> denatured state. Each denaturation curve was analyzed to estimate thermodynamic
parameters, DeltaGD0,value of Gibbs free energy change (DeltaGD) associated with
the urea-induced denaturation, Cm (midpoint of denaturation) and m
(=deltaDeltaGD/delta[urea]). We further performed molecular dynamics simulation
of CAIX for 50ns to see the dynamics of protein structure in the presence of
different urea concentrations. An excellent agreement was observed between in
silico and in vitro studies.
PMID- 28688948
TI - Kondogogu gum-Zn+2-pectinate emulgel matrices reinforced with mesoporous silica
for intragastric furbiprofen delivery.
AB - Flurbiprofen (FLU), a non-steroidal anti-inflammatory drug, exhibits limited
clinical response due to its poor physicochemical properties. This study aimed at
developing reliable drug carriers for intrgastric FLU delivery with a view to
improve biopharmaceutical characteristics of drug and modulate its release in a
controlled manner. In this context, FLU-loaded kondogogu gum (KG)-Zn+2-low
methoxyl (LM) pectinate emulgel matrices reinforced with calcium silicate (CS)
were accomplished by ionotropic gelation technique employing zinc acetate as
cross-linker and characterized for their in vitro performances. All the
formulations demonstrated excellent drug encapsulation efficiency (DEE, 46-87%)
and sustained drug release behavior (Q7h, 70-91%). These quality attributes were
remarkably influenced by polymer-blend (LM pectin:KG) ratios, low-density oil
types and CS inclusion. The drug release profile of the FLU-loaded optimized
matrices (F-7) was best fitted in Korsmeyer-Peppas model with Fickian diffusion
driven mechanism. It also conferred excellent in vitro gastroretention
capabilities. Moreover, the drug-excipient compatibility, alteration of
crystallinity and thermal behavior of drug and surface morphology of matrices
were evidenced with the results of FTIR, XRD, DSC and SEM analyses, respectively.
Thus, the newly developed matrices are appropriate for sustained intragastric FLU
delivery and simultaneous zinc supplementation for effective inflammation and
arthritis management.
PMID- 28688949
TI - Enamel defects and aphthous stomatitis in celiac and healthy subjects: Systematic
review and meta-analysis of controlled studies.
AB - OBJECTIVES: The aim of this systematic review was to compare the presence of
enamel defects and aphthous stomatitis between celiac patients and healthy
controls. DATA SOURCES: A systematic review of articles selected from MEDLINE,
EMBASE and Google Scholar was performed by two independent operators. Additional
studies hand-searched and found in the principal dental and gastroenterology
journals were included. STUDY SELECTION: Only controlled studies on celiac
patients compared to healthy subjects were included. DATA EXTRACTION: Independent
extraction of articles by 2 authors using predefined data fields, including study
quality indicators. DATA SYNTHESIS: In total, the celiac patients had greater
frequency of enamel defects (odds ratio=5.69, 95%CI from 3.47 to 9.33, P<0.00001,
I2=90%, 30 studies). Considering only the children, the odds ratio was 5.63
(95%CI from 3.95 to 8.01, P<0.00001, I2=65%, 24 studies), while in the adults the
odds ratio was not significant (odds ratio=2.16, 95%CI from 0.95 to 4.88, P=0.06,
I2=40%, 3 studies). In total, the celiac patients had greater frequency of
aphthous stomatitis (odds ratio=3.79, 95%CI from 2.67 to 5.39, P<0.00001, I2=49%,
21 studies). Considering only the children, the odds ratio was 4.31 (95%CI from
3.03 to 6.13, P<0.00001, I2=29%, 13 studies), while in the adults the odds ratio
was 47.90 (95%CI from 6.29 to 364.57, P=0.0002, 1 study). CONCLUSIONS: In
children, celiac disease was associated with both enamel defects and aphthous
stomatitis. The odds ratio estimates, however, should be interpreted with caution
due to the high risk of bias showed by all the studies. In adults, the
association between celiac disease and enamel defects or aphthous stomatitis was
unclear because very few studies were performed on this population. CLINICAL
SIGNIFICANCE: The presence of enamel defects and/or aphthous stomatitis in a
child affected by other typical or atypical symptoms of celiac disease represents
an indication for further diagnostic exams for celiac disease.
PMID- 28688950
TI - Ten-year outcome of zirconia ceramic cantilever resin-bonded fixed dental
prostheses and the influence of the reasons for missing incisors.
AB - OBJECTIVES: This clinical study evaluated the long-term outcome and survival rate
of all-ceramic cantilever resin-bonded fixed dental prostheses (RBFDPs) made of
zirconia-ceramic with a single-retainer design to replace missing incisors. In
addition, whether the reason for missing incisors has an influence on the
longevity of RBFDPs was analyzed. MATERIALS AND METHODS: One hundred and eight
zirconia ceramic cantilever RBFDPs were provided for 87 patients. Seventy-five
RBFDPs replaced maxillary incisors and 33 mandibular incisors. The restorations
were subsequently categorized into 3 groups according to the reasons for missing
teeth (congenitally missing, trauma and other reasons). The patients were
followed up annually, and the restorations were assessed for function and
aesthetics. The mean observation time of the RBFDPs was 92.2+/-33months. RESULTS:
Six debondings and 1 loss of restoration were recorded. The lost restoration was
removed at the patient's request after a small chip occurred on the mesial edge
of the pontic. Three of the 6 observed debondings were caused by traumatic
incidents. All debonded RBFDPs were rebonded successfully with no further
complications. Zirconia ceramic RBFDPs yielded a 10-year survival rate of 98.2%
and a success rate of 92.0%. CONCLUSIONS: Anterior zirconia ceramic cantilever
RBFDPs provided excellent clinical longevity. The reasons for missing incisors
did not influence the longevity of the cantilever RBFDPs.
PMID- 28688951
TI - Non-contrast-enhanced 3D MR portography within a breath-hold using compressed
sensing acceleration: A prospective noninferiority study.
AB - PURPOSE: To evaluate images of non-contrast-enhanced 3D MR portography within a
breath-hold (BH) using compressed sensing (CS) compared to standard respiratory
triggered (RT) sequences. MATERIALS AND METHODS: Fifty-nine healthy volunteers
underwent MR portography using two sequences of balanced steady-state free
precession (bSSFP) with time-spatial labeling inversion pulses (Time-SLIP): BH
bSSFP-CS and RT bSSFP. Two radiologists independently scored the diagnostic
acceptability to delineate the portal branches (MPV: main portal vein; RPV: right
portal vein; LPV: left portal vein; RPPV: right posterior portal vein; and P4 and
P8: portal branch of segment 4 and segment 8, respectively) and the overall image
quality on a four-point scale. We assessed noninferiority of BH bSSFP-CS to RT
bSSFP. For quantitative analysis, vessel-to-liver contrast (Cv-l) was calculated
in MPV, RPV and LPV. RESULTS: BH bSSFP sequence was successfully performed with a
30-second acquisition time. The diagnostic acceptability scores of BH bSSFP-CS
compared with RT bSSFP were statistically noninferior: MPV (95% CI for score
difference of Reader 1 and Reader 2, respectively: [-0.16, 0.06], [-0.05, 0.02]),
RPV ([-0.00, 0.11], [-0.01, 0.08]), LPV ([-0.03, 0.10], [-0.10, 0.03]), RPPV ([
0.03, 0.10], [-0.05, 0.05]), P4 ([-0.13, 0.34], [-0.28, 0.21]) and P8 ([-0.21,
0.11], [-0.25, -0.02]). However, the overall image quality of BH bSSFP-CS did not
show noninferiority ([-0.61, -0.24], [-0.54, -0.17]). Cv-l values were
significantly lower in BH bSSFP-CS (P<0.001). CONCLUSION: CS enabled non-contrast
enhanced 3D bSSFP MR portography to be performed within a BH while maintaining
noninferior diagnostic acceptability compared to standard RT bSSFP MR
portography.
PMID- 28688952
TI - Left-ventricular mechanics in children with hypertrophic cardiomyopathy. CMR
study.
AB - OBJECTIVES: To assess the magnitude of myocardial displacement abnormalities and
their alterations with the fibrosis, left-ventricular (LV) outflow tract
obstruction (LVOTO) and hypertrophy in juveniles with hypertrophic cardiomyopathy
(HCM). STUDY DESIGN: Fifty-five children [age 12,5+/-4.6years, 38 (69,1%) males,
19 (34,5%) with LVOTO] with HCM and 20 controls underwent cardiovascular magnetic
resonance. The LV feature tracking (FT) derived strain and strain rates were
quantified. Results of FT analysis were compared between HCM subjects and
controls and between children with and without LVOTO. RESULTS: Children with HCM
exhibited decreased strain in both hypertrophied and nonhypertrophied segments
versus controls. LV global longitudinal strain (LVGLS) rate (-0.69+/-0.04 vs
0.91+/-0.05, p=0,04), LV circumferential strain (LVCR) rate (-0.98+/-0.09 vs
1.27+/-0.06, p=0,02), LV radial strain (LVR) (18,5+/-1.9 vs 27,4+/-1.4, p<0,01)
and LVR rate (0,98+/-0.1 vs 1,53+/-0.08, p<0,01) were substantially compromised
in subjects with LVOTO vs without. In multivariable regression all LV myocardial
dynamics markers, except for LVCR, exhibited a significant association with the
degree of LVOTO. LVCR rate (beta=0,31, p=0,02) and LVR (beta=-0.24, p=0,04) were
related to LV mass and only LVCR rate (beta=0,15, p=0,03) was associated with the
amount of LV fibrosis. CONCLUSIONS: The reduction of all indices of LV myocardial
mechanics in juvenile HCM patients was global but particularly pronounced in
hypertrophied segments of the LV. The majority of the LV strains and strain rates
were substantially compromised in subjects with LVOTO compared to patients
without the obstruction. Myocardial mechanics indices seemed to be related to the
degree of LVOTO rather than either to mass or the amount of fibrosis.
PMID- 28688953
TI - Antrodia camphorata inhibits metastasis and epithelial-to-mesenchymal transition
via the modulation of claudin-1 and Wnt/beta-catenin signaling pathways in human
colon cancer cells.
AB - ETHNOPHARMACOLOGICAL RELEVANCE: Antrodia camphorata (AC) is a well known
traditional Chinese medicinal mushroom in Taiwan, has been used to treat various
diseases including cancer. MATERIALS AND METHODS: In this study, we investigated
the anti-metastatic and anti-EMT properties of a fermented culture broth of AC in
human colon SW480claudin-1- and metastatic SW620claudin-1+ cancer cells in vitro.
RESULTS: AC down-regulates claudin-1 and inhibits the proliferation and colony
formation abilities of both SW620claudin-1+ and SW480claudin-1- cells. In highly
metastatic SW620claudin-1+ cells, non-cytotoxic concentrations of AC
significantly inhibited migration/invasion, accompanied by the down-regulation of
MMP-2 and MMP-9 proteins. AC decreased nuclear translocation of Wnt/beta-catenin
through a GSK3beta-dependent pathway. AC consistently inhibited EMT by up
regulating the epithelial and downregulating the mesenchymal marker proteins. In
SW480claudin-1- cells, AC suppressed migration/invasion potentially through the
inhibition of the PI3K/AKT/NFkappaB signaling pathways without altering the
expression levels of beta-catenin and GSK3beta proteins. CONCLUSION: Altogether,
this study demonstrates the anti-metastatic and anti-EMT activities of AC, which
may contribute to the development of a chemopreventive agent for colon cancer.
PMID- 28688955
TI - Mechanisms of fosfomycin resistance in carbapenem-resistant Enterobacter sp.
AB - We report on fosfomycin susceptibility and mechanisms of resistance in clinical
strains of blaKPC-positive Enterobacter sp. (n = 19). A total of 14 strains (74%)
were susceptible to fosfomycin; 8 strains (42%) were positive for fosA and no
strains were positive for FosA3 or FosC2. FosA presence does not appear to
correlate with susceptibility.
PMID- 28688954
TI - Rifampicin-induced injury in HepG2 cells is alleviated by TUDCA via increasing
bile acid transporters expression and enhancing the Nrf2-mediated adaptive
response.
AB - Bile acid transporters and the nuclear factor erythroid 2-related factor (Nrf-2)
mediated adaptive response play important roles in the development of drug
induced liver injury (DILI). However, little is known about the contribution of
the adaptive response to rifampicin (RFP)-induced cell injury. In this study, we
found RFP decreased the survival rate of HepG2 cells and increased the levels of
lactate dehydrogenase (LDH), alanine aminotransferase (ALT), aspartate
aminotransferase (AST), alkaline phosphatase (AKP), gamma-glutamyl-transferase
(gamma-GT), total bilirubin (TBIL), direct bilirubin (DBIL), indirect bilirubin
(IBIL), total bile acid (TBA) and adenosine triphosphate (ATP) in the cell
culture supernatants in both a concentration- and a time-dependent manner. RFP
increased the expression levels of bile acid transporter proteins and mRNAs, such
as bile salt export pump (BSEP), multidrug resistance protein 1 (MDR1), multidrug
resistance-associated protein 2 (MRP2), Na+/taurocholate cotransporter (NTCP),
organic anion transporting protein 2 (OATP2), organic solute transporter beta
(OSTbeta) and Nrf2. Following the transient knockdown of Nrf2 and treatment with
RFP, the expression levels of the BSEP, MDR1, MRP2, NTCP, OATP2 and OSTbeta
proteins and mRNAs were decreased to different degrees. Moreover, the cell
survival was decreased, whereas the LDH level in the cell culture supernatant was
increased. Overexpression of the Nrf2 gene produced the opposite effects.
Treatment with tauroursodeoxycholic acid (TUDCA) increased the expression levels
of the bile acid transporters and Nrf2, decreased the expression levels of
glucose-regulated protein 78 (GRP78), PKR-like ER kinase (PERK), activating
transcription factor 4 (ATF4), and C/EBP-homologous protein (CHOP), and inhibited
RFP-induced oxidative stress. Moreover, TUDCA reduced cell apoptosis, increased
cell survival and decreased the levels of LDH, ALT, AST, AKP, gamma-GT, TBIL,
DBIL, IBIL, TBA and ATP in the cell culture supernatant. Therefore, TUDCA
alleviates RFP-induced injury in HepG2 cells by enhancing bile acid transporters
expression and the Nrf2-mediated adaptive response.
PMID- 28688956
TI - Flavonoid glycosides from Barringtonia acutangula.
AB - Using various chromatographic separation techniques, ten flavonoid glycosides,
including six new compounds namely barringosides A-F (1-6), were isolated from a
methanol extract of the Barringtonia acutangula leaves. The structure elucidation
was confirmed by spectroscopic analyses, including 1D and 2D NMR, and HR ESI MS.
Their inhibitory effects on LPS-induced NO production in RAW264.7 cells were also
evaluated. Among the isolated compounds, quercetin 3-O-beta-d-(6-p
hydroxybenzoyl)galactopyranoside (9) showed significant effect with an IC50 of
20.00+/-1.68uM. This is the first report of these flavonoid glycosides from
Barringtonia genus and their inhibition on LPS-induced NO production in RAW264.7
cells was reported here for the first time.
PMID- 28688957
TI - Discovery of highly selective kappa-opioid receptor agonists: 10alpha-Hydroxy TRK
820 derivatives.
AB - kappa-Opioid receptor agonists with high selectivity over the MU-opioid receptor
are attractive targets in the development of drugs for pain and pruritus. We
previously reported the synthesis of 10alpha-hydroxy TRK-820 (1). In this study,
we elucidated the biological properties of 1 and optimized its 6-acyl unit by
modifying our synthetic route. Among the 10alpha-hydroxy TRK-820 derivatives
prepared, 26 showed the most potent kappa-opioid agonist activity
(EC50=0.00466nM) and excellent selectivity and 22 was the most kappa-selective
agonist.
PMID- 28688958
TI - Novel derivatives of deoxycholic acid bearing aliphatic or cyclic diamine
moieties at the C-3 position: Synthesis and evaluation of anti-proliferative
activity.
AB - A new library of deoxycholic acid derivatives bearing nitrogen-containing
moieties at the C-3 position was synthesised from epoxy derivative 1 via an
epoxide ring-opening reaction promoted by aliphatic or cyclic diamines and fully
characterised by NMR and mass-spectroscopy. The synthesised compounds were
screened for cytotoxicity against four human tumour cell lines. The results
showed that some of the novel diamine-bearing derivatives displayed improved anti
proliferative activities over the parent compound DCA. Among them, a 1
methylpiperazine containing compound (6) showed promising activity and the
highest selectivity against tumour cells of enterohepatic origin (HepG2:
IC50=3.6uM, SI=9.0; HuTu-80: IC50=4.6uM, SI=6.9) and was identified as a lead
molecule.
PMID- 28688959
TI - From gene to therapy in spinal and bulbar muscular atrophy: Are we there yet?
AB - Abnormal polyglutamine expansions in the androgen receptor (AR) cause a muscular
condition, known as Kennedy's disease or spinal and bulbar muscular atrophy
(SBMA). The disease is transmitted in an X-linked fashion and is clinically
characterized by weakness, atrophy and fasciculations of the limb and bulbar
muscles as a result of a toxic gain-of-function of the mutant protein. Notably,
affected males also show signs of androgen insensitivity, such as gynaecomastia
and reduced fertility. The characterization of the natural history of the
disease, the increasing understanding of the mechanism of pathogenesis and the
elucidation of the functions of normal and mutant AR have offered a momentum for
developing a rational therapeutic strategy for this disease. In this special
issue on androgens and AR functions, we will review the molecular, biochemical,
and cellular mechanisms underlying the pathogenesis of SBMA. We will discuss
recent advances on therapeutic approaches and opportunities for this yet
incurable disease, ranging from androgen deprivation, to gene silencing, to an
expanding repertoire of peripheral targets, including muscle. With the
advancement of these strategies into the clinic, it can be reasonably anticipated
that the landscape of treatment options for SBMA and other neuromuscular
conditions will change rapidly in the near future.
PMID- 28688960
TI - The lowering of bilirubin levels in patients with neonatal jaundice using massage
therapy: A randomized, double-blind clinical trial.
AB - OBJECTIVE: Due to the effects of massage on various laboratory parameters
(including those related to jaundice) in infants and the expansion of existing
studies to achieve effective and safe therapy in the treatment of neonatal
jaundice, this study aimed to investigate the effect of massage on bilirubin
levels in cases of neonatal jaundice. METHODS: In this study, 134 patients were
randomly assigned to either an intervention group (massage combined with
phototherapy, n=67) or a control group (phototherapy only, n=67). In both groups,
serum total bilirubin level and frequency of daily bowel movements were measured
and compared during each of the first four days of treatment. RESULTS: Baseline
levels of bilirubin were similar between the two groups (P>0.05). During the
measurements obtained post-intervention, significant differences surfaces between
the two groups in bilirubin levels and frequency of daily bowel movements (P<0.05
for both). No significant relationship was observed during days 1 and 2 of
massage therapy between daily frequency of bowel movements and serum bilirubin
level (P>0.05); this relationship became significant during the third and fourth
days (P<0.05). CONCLUSION: Massage therapy combined with phototherapy is an
effective method for reducing serum total bilirubin in infants with neonatal
jaundice.
PMID- 28688961
TI - Active sleep is associated with the face preference in the newborns who
familiarized with a responsive face.
AB - Aim of this study was to investigate the preferential looking behaviour,
subsequent to a familiarization task (8-min) with a previously responsive or
motionless face, before and after a sleep cycle. Moreover, the role of the active
sleep in memory consolidation of the responsive or motionless faces was explored.
Hypotheses were that the newborns undergoing a motionless familiarization will
exhibit a novelty effect (preference for the novel face) whereas the newborns
undergoing a responsive familiarization will show a familiarity effect
(preference for the known face) before and after the sleep cycle; moreover, the
amount of active sleep will be associated with the looking time at the known face
after a sleep cycle. Forty-five healthy full-term newborns were randomly assigned
to two groups (group 1: motionless-familiarization and group 2: responsive
familiarization); in both groups newborns were video-recorded during four post
familiarization face-preference tasks, two of them performed before and two after
a sleep cycle. During the pre-sleep-trials, there was not a significant
preference for one face in both groups. During the post-sleep trials, the
newborns showed a clear preference for the novel face. This effect was more
evident in group 1. Only in group 2 there was a significant positive correlation
between the active sleep duration and the looking duration at the known-face
during the post-sleep trials (r=0.41; p=0.040). Multiple regression confirmed
that only in the group 2 the total duration of the active sleep was associated
with the looking duration at the known-face during the post-sleep trials
(Adjusted R2=0.13; beta=0.41; t=2.2; p=0.040). Findings showed that in newborns
the face representation can be recalled after a sleep cycle. Moreover, the amount
of the active sleep predicted the post-sleep looking toward the known-face only
in the newborns who interactively familiarized with the face.
PMID- 28688962
TI - Stress, cell senescence and organismal ageing.
AB - Cellular senescence was first described by Hayflick and Moorhead in the 1960s as
the irreversible arrest of cells following prolonged cultivation. Telomere
shortening is the key mechanism driving replicative senescence in human
fibroblasts. Later, pioneering work by Olivier Toussaint and others showed that
stress plays a major role in the induction of senescence in vitro, a phenomenon
known as stress-induced premature senescence or SIPS. It is also now widely
accepted that senescence plays a role in vivo. An emerging body of evidence from
animal models, and particularly mice, has demonstrated an important role for
senescence in several processes such as embryonic development, wound healing,
tumour suppression and ageing. However, mostly due to a lack of availability of
tissues and specific markers, less is known about the importance of cell
senescence in humans. In this review, we summarize some of the key findings in
the field of senescence, stress-induced senescence and telomeres. We focus
particularly on the role of telomere dysfunction and senescence during the ageing
process as well as potential interventions, including pharmacological approaches
like telomerase activators and senolytics, to counteract their detrimental
effects in ageing and disease.
PMID- 28688963
TI - Continuous interscalene brachial plexus blockade is associated with reduced
length of stay after shoulder arthroplasty.
AB - BACKGROUND: Catheter-delivered continuous interscalene anesthesia has
demonstrated improved pain control in randomized clinical trials. The purpose of
this study is to determine whether the introduction of continuous catheter
anesthesia was associated with a change in length of stay (LOS), readmission,
rates of discharge home without home health or nursing services, or opioid
administration. We hypothesized that the introduction of continuous catheter
anesthesia would be associated with a decrease in LOS, readmission, non-home
discharge, and opioid administration. METHODS: During 2012, our center
transitioned from ultrasound-guided single-dose interscalene regional anesthesia
to combined single-dose anesthesia and additional continuous catheter anesthesia
over 48-72hours. This retrospective chart review compared primary shoulder
arthroplasties with single-dose anesthesia to those with continuous catheter
anesthesia, after excluding the learning curve, with univariate and multivariate
analyses. RESULTS: In total, 1697 patients met criteria, 41% with single-dose
anesthesia and 59% with continuous catheter anesthesia. On univariate analysis,
the continuous catheter group LOS was 2.2+/-0.7 day and single-dose group LOS was
2.5+/-0.8 days (P<=0.001). One day LOS's comprised 1% of the single-dose group
and 27% of the continuous catheter group (P<0.001). Anesthesia type remained a
significant predictor on multivariate analysis (P<0.001) Readmission at 30 and 90
days (P=0.091 and 0.576), and home discharge (P=0.456) were not different. Opioid
administration was higher in the continuous catheter group on univariate analysis
(P<0.001), but not on multivariate analysis (P=0.607). CONCLUSION: In this
retrospective review of 1697 primary shoulder arthroplasties performed at our
high-volume, referral center, continuous catheter anesthesia was associated with
reduced length of stay when compared to single-dose anesthesia. LEVEL OF
EVIDENCE: Therapeutic, level IV.
PMID- 28688964
TI - Ageing and thought suppression performance: Its relationship with working memory
capacity, habitual thought suppression and mindfulness.
AB - A study investigated how the ability to suppress thoughts in the laboratory was
affected by type of thought suppressed (positive, negative, neutral),
participants' age and working memory capacity (WMC). Linked variables (Use of
thought suppression, social desirability, and mindfulness) were measured to
assess whether they modified susceptibility to thought intrusion. Younger, middle
aged and older adults suppressed three different valenced thoughts in a
counterbalanced order for 5-min per thought. Participants then completed a WMC
task and questionnaire measures of the linked variables. Valence had no effect on
intrusions. WMC was positively related to intrusions; higher WMC corresponded to
greater intrusions. Age was negatively related to intrusions; with increasing age
intrusions decreased. Hierarchical regression showed only age and backward digit
span (WMC) significantly predicted intrusions. The relationship between WMC and
intrusions was not moderated by age. WMC and age both independently predict level
of intrusion, and no synergistic effect was found.
PMID- 28688965
TI - Kinetic and amperometric study of the MtPerII peroxidase isolated from the
ascomycete fungus Myceliophthora thermophila.
AB - The enzyme MtPerII is a new peroxidase which has been isolated only recently from
fungus Myceliophthora thermophila and has significant thermostability and
stability at high H2O2 concentrations. In the present work, an electrochemical
kinetic study, based on cyclic voltammetry, is performed for the first time for
the catalytic decomposition of H2O2 by MtPerII, at 18 degrees C. Leuco methylene
blue (LMB) is used as a mediator and the catalytic and Michaelis constants are
determined, assuming a Michaelis-Menten mechanism. Experimental evidence suggest
the absence of inhibition by H2O2, for concentrations up to 16mM, and increasing
catalytic activity for temperatures up to 50 degrees C. Moreover, a modified
electrode is constructed, by attempting the entrapment of MtPerII on a
dodecanothiol self-assembled monolayer on gold. The modified electrode is studied
chronoamperometrically in solutions containing methylene blue mediator and
different concentrations of H2O2. It is shown that adsorbed MtPerII retains its
activity and the modified electrode exhibits a considerably high linear region
for the detection of H2O2. The experimental findings indicate that MtPerII is a
new candidate for analytical and industrial applications.
PMID- 28688966
TI - Surgical outcomes of pancreaticoduodenectomy in young patients: A case series.
AB - BACKGROUND: Pancreaticoduodenectomy (PD) is a complex procedure for management
periampullary neoplasms The aim of our work is to report the surgical outcomes
after PD in young adult (YA) (<35 years) and to compare it to a adult patients
who underwent PD. METHODS: We retrospectively analyzed the data of all patients
who underwent PD in the period from January 1993 to December 2016. The primary
outcome was the rate of total postoperative complications. Secondary outcomes
included postoperative pathology, exocrine and endocrine function and survival
rate. RESULTS: 58/975 patients (5.9%) were YA and the majority of them were
females. The incidence of post-operative complications in the YA was comparable
to that in the adult group. Delayed gastric emptying developed significantly in
adult group than YA group (0.008). The overall survival was significantly higher
in the YA (P = 0.0001). The most common pathology in the YA was adenocarcinoma
(41.4%) and solid pseudopapillary tumor (SPT) (29.3%). No significant difference
as regards postoperative pancreatic exocrine and endocrine function in both
groups. CONCLUSION: PD in YA when performed in tertiary centers with good
surgical experience is safe. The most common pathological diagnosis in the YA was
adenocarcinoma followed by SPT.
PMID- 28688967
TI - Personality Factors Associated With Resident Performance: Results From 12
Accreditation Council for Graduate Medical Education Accredited Orthopaedic
Surgery Programs.
AB - OBJECTIVES: To understand the personality factors associated with orthopedic
surgery resident performance. DESIGN: A prospective, cross-sectional survey of
orthopedic surgery faculty that assessed their perceptions of the personality
traits most highly associated with resident performance. Residents also completed
a survey to determine their specific personality characteristics. A subset of
faculty members rated the performance of those residents within their respective
program on 5 dimensions. Multiple regression models tested the relationship
between the set of resident personality measures and each aspect of performance;
relative weights analyses were then performed to quantify the contribution of the
individual personality measures to the total variance explained in each
performance domain. Independent samples t-tests were conducted to examine
differences between the personality characteristics of residents and those
faculty identified as relevant to successful resident performance. SETTING: Data
were collected from 12 orthopedic surgery residency programs1 throughout the
United States. The level of clinical care provided by participating institutions
varied. PARTICIPANTS: Data from 175 faculty members and 266 residents across 12
programs were analyzed. RESULTS: The personality features of residents were
related to faculty evaluations of resident performance (for all, p < 0.01); the
full set of personality measures accounted for 4%-11% of the variance in ratings
of resident performance. Particularly, the characteristics of agreeableness,
neuroticism, and learning approach were found to be most important for explaining
resident performance. Additionally, there were significant differences between
the personality features that faculty members identified as important for
resident performance and the personality features that residents possessed.
CONCLUSION: Personality assessments can predict orthopedic surgery resident
performance. However, results suggest the traits that faculty members value or
reward among residents could be different from the traits associated with
improved resident performance.
PMID- 28688968
TI - Are Surgical Milestone Assessments Predictive of In-Training Examination Scores?
AB - OBJECTIVES: With the recent utilization of Accreditation Council for Graduate
Medical Education developmental milestones as part of resident evaluation, we
sought to explore whether milestone-based ratings were associated with American
Board of Surgery In-Training Examination (ABSITE) scores. METHODS: Mid-year
milestone ratings were obtained from the Accreditation Council for Graduate
Medical Education Accreditation Database System for years 2014, 2015, and 2016
for all postgraduate years 1-5 general surgery residents in our program and
paired with ABSITE scores (n = 69) from January of the following year. Linear
regression was used to assess predictor importance of milestones on both ABSITE
percentage correct scores and ABSITE percentile scores. RESULTS: Minimal to small
positive correlations were observed between milestones and ABSITE percentile
scores (r = 0.09-0.25), while moderately large correlations were observed between
milestones and percentage correct scores (r = 0.65-0.76). The Medical Knowledge 1
(MK1) milestone significantly predicted ABSITE percentage correct scores, and
explained 60% of the variance (adjusted R2 = 0.603). MK1 also significantly
predicted ABSITE percentile scores, although weaker in magnitude, with MK1
explaining 20% of the variance (adjusted R2 = 0.197). Postgraduate year level and
other milestones were not influential predictors of ABSITE scores. CONCLUSIONS:
The mid-year MK1 milestone rating was predictive of ABSITE scores and may serve
as a useful marker for Clinical Competency Committees to identify residents who
could benefit from additional support to prepare for the ABSITE, although given
the small exploratory nature of this study, additional research is still needed.
PMID- 28688969
TI - The Steinberg Centre for Simulation and Interactive Learning at McGill
University.
AB - Simulation allows for learner-centered health professions training by providing a
safe environment to practice and make mistakes without jeopardizing patient care.
It was with this goal in mind that the McGill Medical Simulation Center was
officially opened on September 14, 2006, as a partnership between McGill
University, the Faculty of Medicine and its affiliated hospitals. Its mandate is
to provide state-of-the-art facilities to support simulation-based medical and
allied health education initiatives. Since its inception, the center, recently
renamed the Steinberg Center for Simulation and Interactive Learning (SCSIL), has
undergone a major expansion and logged more than 130,000 learner visits.
Educational activities are offered at all levels of medical and allied health
care training, and include standardized patient encounters, partial task
trainers, multidisciplinary courses, and high-fidelity trainers, among many
others. In addition to its educational mandate, the center also supports an
active research program, programs to enhance collaboration with disciplines
outside of health care to spur innovation, and community outreach initiatives.
PMID- 28688970
TI - Secretory Stanniocalcin 1 promotes metastasis of hepatocellular carcinoma through
activation of JNK signaling pathway.
AB - The hypoxic microenvironment is well-characterized in hepatocellular carcinoma
(HCC). Delineation of hypoxia-responsive events is an integral part to understand
the pathogenesis of HCC. We studied the functional role and clinical relevance of
Stanniocalcin 1 (STC1), a hypoxia-induced molecular target, in HCC. In our
clinical cohort, STC1 transcript was up-regulated in HCC tumor tissues. Moreover,
STC1 protein was detected in the sera of HCC patients. A higher serum STC1 level
was correlated with larger tumor size and poorer 5-year disease-free survival.
Functionally, recombinant STC1 protein (rhSTC1) promoted cell migration and cell
invasion in vitro; and the effect was abolished by co-treatment of anti-STC1
neutralizing antibody. By in vivo mouse model, silencing of STC1 in HCC cells
downregulated secretory STC1 level and suppressed lung metastasis. Furthermore,
we found that rhSTC1 activated the JNK pathway, as evidenced by altered
expression of the key molecular targets pJNK and p-c-Jun. The functional effects
conferred by rhSTC1 were abrogated by co-treatment of JNK inhibitor. In summary,
secretory STC1 enhances metastatic potential of HCC via JNK signaling. It
potentially serves as a prognostic serum biomarker and a therapeutic target for
HCC.
PMID- 28688971
TI - Tumor vessel normalization by the PI3K inhibitor HS-173 enhances drug delivery.
AB - Tumor vessels are leaky and immature, which causes poor oxygen and nutrient
supply to tumor vessels and results in cancer cell metastasis to distant organs.
This instability of tumor blood vessels also makes it difficult for anticancer
drugs to penetrate and reach tumors. Numerous tumor vessel normalization
approaches have been investigated for improving drug delivery into tumors. In
this study, we investigated whether phosphoinositide 3-kinase (PI3K) inhibitors
are able to improve vascular structure and function over the prolonged period
necessary to achieve effective vessel normalization. The PI3K inhibitors, HS-173
and BEZ235 potently suppressed tumor growth and hypoxia, and increased tumor
apoptosis in animal models. PI3K inhibitors also induced a regular, flat
monolayer of endothelial cells (ECs) in vessels, improving stability of vessel
structure, and normalized tumor vessels by increasing vascular maturity, pericyte
coverage, basement membrane thickness, and tight-junctions. These effects
resulted in a decrease in tumor vessel tortuosity and vessel thinning, and
improved vessel function and blood flow. The tumor vessel stabilization effect of
the PI3K inhibitor HS-173 also decreased the number of metastatic lung nodules in
vivo metastasis model. Furthermore, HS-173 improved the delivery of doxorubicin
into the tumor region, enhancing its anticancer effects. Mechanistic studies
suggested that PI3K inhibitor HS-173-induced vessel normalization reflected
changes in endothelial Notch signaling. Taken together, our findings indicate
that vessel normalization by PI3K inhibitors restrained tumor growth and
metastasis while improving chemotherapy by enhancing drug delivery into the
tumor, suggesting that HS-173 may have a therapeutic value as an enhancer or an
anticancer drug.
PMID- 28688972
TI - Suppression of angiogenesis and tumour progression by combretastatin and
derivatives.
AB - The search for small molecule inhibitors has gained prominence with the
recognition of their inherent advantage for cancer therapy. Combretastatin is a
naturally occurring small stilbenoid. By virtue of the ability to bind to tubulin
combretastatin and its derivatives promote depolymerisation of microtubules as
well as inhibit tubulin polymerisation. This suppresses cell proliferation
signalling and induces apoptosis. Combretastatins activate mitotic checkpoints
that lead to mitotic catastrophe and apoptosis. They subvert the signalling
systems which stimulate invasion, activate EMT (epithelial mesenchyme transition)
and promote tumour progression. Allied with the ability to suppress angiogenesis
these compounds have been viewed as potential inhibitors of metastasis. The
notion of merging RTK (receptor tyrosine kinase) inhibition with suppression of
invasion and possible inhibition of EMT has contributed to the credibility of
combretastatins as anti-cancer agents. Invaluable are their attributes of
inhibiting tumour growth and induction of apoptosis and necrosis by reducing
blood supply to the tumour. Aside from these biological effects, this commentary
also discusses the issues of the targeting of combretastatins to the tumour
vasculature and effective delivery of the drugs encapsulated in nanospheres.
Notwithstanding the perceived benefits, one can see a compelling need to
understand the effects of combretastatin on the actin cytoskeletal dynamics and
the disruption of microtubule polymerisation, and whether it is more efficient a
tumour inhibitor than the conventional drugs that target microtubule dynamics.
Combinations of combretastatins with other vascular disrupting agents have been
attempted. It is essential to establish the perceived inhibition of EMT beyond
reasonable doubt. This might justify using the combretastatins with allosteric
EMT and Akt inhibitors as additional choices for pre-clinical/clinical studies.
PMID- 28688973
TI - PD-1/PD-L1 checkpoint blockades in non-small cell lung cancer: New development
and challenges.
AB - PD-1/PD-L1 checkpoint blockades have dramatically changed the landscape for
second-line treatment of non-small cell lung cancer (NSCLC). Based on the
promising results of Keynote-024 presented so far, pembrolizumab has been
approved as first-line treatment for advanced PD-L1 positive NSCLC patients.
However, overall response rate (ORR) is limited to PD-1/PD-L1 checkpoint
blockades when used as single agent. Combining with chemotherapy, anti-CTLA-4
antibodies, targeted therapy, radiotherapy or other treatment options is
perceived as an appealing method aimed at achieving higher efficacy. There are
many clinical trials on going or finished assessing the efficacy and safety of
the PD-1/PD-L1 blockades alone or combining with other approaches in first-line
or second-line treatments. A lot of challenges need to be overcome before PD-1/PD
L1 checkpoint blockades are widely used in the patients with NSCLC including the
identification of optimal combination, treatment-related adverse effects, the
high cost and lack of effective predictive markers. In this review, we focus on
outlining current clinical trials and challenges for future research of PD-1/PD
L1 pathway checkpoint blockades in NSCLC.
PMID- 28688974
TI - A step forward in the understanding of the presence and expansion of Echinococcus
multilocularis in Eastern Europe using microsatellite EmsB genotyping in Poland.
AB - Alveolar echinococcosis is a severe zoonotic disease caused by the parasite
Echinococcus multilocularis. In Europe, the lifecycle of this cestode is mainly
sylvatic based on a prey-predator interaction between the red fox and small
rodents as definitive and intermediate hosts, respectively. National surveillance
of E. multilocularis in red foxes in Poland has reported a clear distinction
between low endemic areas (from 2 to 5.7%) in the western half and high endemic
areas (11.8 to 50.0%) in the eastern half of the country. A drastic increase of
prevalence has been observed in the eastern half of Poland since the 2000's.
Microsatellite EmsB genotyping was performed on 301 E. multilocularis worms from
87 foxes sampled throughout Poland, leading to identification of 29 EmsB
profiles. The main profile, Pol19, was identified across the country and
accounted for 44.9% of the worms collected. The conformity of 18 Polish profiles
was established by comparison with previous profiles identified in Europe, but
none corresponded to the most common European profiles. Poland was confirmed as a
peripheral area of the main European focus, with more recent colonization by the
parasite. The sharing of common profiles mainly by neighboring provinces was
confirmed by a clustering analysis identifying four main groups. Expansion of the
parasite in Poland in these four groups appears to be influenced by the situation
in neighboring countries. Acquiring EmsB genotyping data from eastern European
countries, for which very few data are reported, is necessary to understand the
expansion of the parasite in the whole of Europe.
PMID- 28688975
TI - Sequence data management for scientific purposes.
PMID- 28688976
TI - Genomic analysis of the marine fish pathogen Photobacterium damselae subsp.
piscicida: Insertion sequences proliferation is associated with chromosomal
reorganisations and rampant gene decay.
AB - Photobacterium damselae subsp. piscicida (Pdp) is an intracellular fish pathogen
that causes photobacteriosis, a disease proven deadly in farmed fish worldwide.
This work focuses on the analysis of genome sequences, chromosomes structure and
gene contents of two strains from Sparus aurata (DI21) and Solea senegalensis
(L091106-03H), isolated on the Spanish Atlantic coast. The comparative genomic
analysis revealed that DI21 and L091106-03H share 98% of their genomes, including
two virulence plasmids: pPHDP70 encoding siderophore piscibactin synthesis and
pPHDP10 encoding the apoptotic toxin AIP56. Both genomes harbour a surprisingly
large number of IS elements accounting for 12-17% of the total genome,
representing an IS density of 0.15 elements per kb, one of the highest IS density
values in a bacterial pathogen. This massive proliferation of ISs is responsible
for the generation of a high number of pseudogenes that caused extensive loss of
biological functions. Pseudogene formation is one of the main features of Pdp
genome that explains most of the ecological and phenotypic differences with
respect to its sibling subspecies P. damselae subsp. damselae and to other
Vibrionaceae. Evidence was also found proving the existence of two chromosomal
configurations depending on the origin of the strains: an European and an
Asian/American types of genome organisation, reinforcing the idea of the
existence of two geographically-linked clonal lineages in Pdp. In short, our
study suggests that the host-dependent lifestyle of Pdp allowed massive IS
proliferation and gene decay processes, which are major evolutionary forces in
the shaping of the Pdp genome.
PMID- 28688977
TI - Prevalence of drug resistance among HIV-1 treatment-naive patients in Greece
during 2003-2015: Transmitted drug resistance is due to onward transmissions.
AB - BACKGROUND: The prevalence of HIV-1 drug resistance among treatment-naive
patients ranges between 8.3% and 15% in Europe and North America. Previous
studies showed that subtypes A and B were the most prevalent in the Greek HIV-1
epidemic. Our aim was to estimate the prevalence of resistance among drug naive
patients in Greece and to investigate the levels of transmission networking among
those carrying resistant strains. METHODS: HIV-1 sequences were determined from
3428 drug naive HIV-1 patients, in Greece sampled during 01/01/2003-30/6/2015.
Transmission clusters were estimated by means of phylogenetic analysis including
as references sequences from patients failing antiretroviral treatment in Greece
and sequences sampled globally. RESULTS: The proportion of sequences with SDRMs
was 5.98% (n=205). The most prevalent SDRMs were found for NNRTIs (3.76%),
followed by N(t)RTIs (2.28%) and PIs (1.02%). The resistance prevalence was 22.2%
based on all mutations associated with resistance estimated using the HIVdb
resistance interpretation algorithm. Resistance to NNRTIs was the most common
(16.9%) followed by PIs (4.9%) and N(t)RTIs (2.8%). The most frequently observed
NNRTI resistant mutations were E138A (7.7%), E138Q (4.0%), K103N (2.3%) and V179D
(1.3%). The majority of subtype A sequences (89.7%; 245 out of 273) with the
dominant NNRTI resistance mutations (E138A, K103N, E138Q, V179D) were found to
belong to monophyletic clusters suggesting regional dispersal. For subtype B,
68.1% (139 out of 204) of resistant strains (E138A, K103N, E138Q V179D) belonged
to clusters. For N(t)RTI-resistance, evidence for regional dispersal was found
for 27.3% and 21.6% of subtype A and B sequences, respectively. CONCLUSIONS: The
TDR rate based on the prevalence of SDRM is lower than the average rate in
Europe. However, the prevalence of NNRTI resistance estimated using the HIVdb
approach, is high in Greece and it is mostly due to onward transmissions among
drug-naive patients.
PMID- 28688978
TI - Molecular characterization of complete genomic segment-2 of picobirnavirus
strains detected in a cat and a dog.
AB - We report here molecular characterization of complete genomic segment-2 of
picobirnavirus (PBV) strains PBV/Cat/KNA/K40/2014 and PBV/Dog/KNA/RVC7/2015
detected in a cat (Felis catus) and a dog (Canis lupus familiaris), respectively,
on the Caribbean island of St. Kitts. To obtain the full-length nucleotide (nt)
sequence of gene segment-2 of the canine and feline PBV strains, the 5'- and 3'-
portions of gene segment-2 containing an overlapping region were amplified using
a non-specific primer-based amplification method with modifications. The complete
gene segment-2 of feline PBV strain K40 and canine PBV strain RVC7 was 1784nt and
1689nt long, respectively, and encoded a putative RNA-dependent RNA polymerase
(RdRp) of 534 amino acid (aa) and 531 aa, respectively. The complete gene segment
2 of strains K40 and RVC7 exhibited a high degree of genetic diversity between
themselves, and with those of PBVs from other host species. On the other hand,
both the canine and feline PBV strains retained the 5'- and 3'- end nucleotide
sequences and the three domains of putative RdRp that are conserved in PBVs. To
our knowledge, this is the first report on molecular characterization of complete
gene segment-2 of PBV strains detected in cats and dogs, allowing us to study the
features of putative RdRps of PBVs in these host species, and providing important
insights into the genetic makeup and evolution of feline and canine PBV strains.
PBVs were detected for the first time in cats and dogs from the Caribbean region.
PMID- 28688979
TI - Remarkable richness of trypanosomes in tsetse flies (Glossina morsitans morsitans
and Glossina pallidipes) from the Gorongosa National Park and Niassa National
Reserve of Mozambique revealed by fluorescent fragment length barcoding (FFLB).
AB - Trypanosomes of African wild ungulates transmitted by tsetse flies can cause
human and livestock diseases. However, trypanosome diversity in wild tsetse flies
remains greatly underestimated. We employed FFLB (fluorescent fragment length
barcoding) for surveys of trypanosomes in tsetse flies (3086) from the Gorongosa
National Park (GNP) and Niassa National Reserve (NNR) in Mozambique (MZ),
identified as Glossina morsitans morsitans (GNP/NNR=77.6%/90.5%) and Glossina
pallidipes (22.4%/9.5%). Trypanosomes were microscopically detected in 8.3% of
tsetse guts. FFLB of gut samples revealed (GNP/NNR): Trypanosoma congolense of
Savannah (27%/63%), Kilifi (16.7%/29.7%) and Forest (1.0%/0.3%) genetic groups;
T. simiae Tsavo (36.5%/6.1%); T. simiae (22.2%/17.7%); T. godfreyi (18.2%/7.0%);
subgenus Trypanozoon (20.2%/25.7%); T. vivax/T. vivax-like (1.5%/5.2%); T.
suis/T. suis-like (9.4%/11.9%). Tsetse proboscises exhibited similar species
composition, but most prevalent species were (GNP/NNR): T. simiae (21.9%/28%), T.
b. brucei (19.2%/31.7%), and T. vivax/T. vivax-like (19.2%/28.6%). Flies
harboring mixtures of trypanosomes were common (~ 64%), and combinations of more
than four trypanosomes were especially abundant in the pristine NNR. The non
pathogenic T. theileri was found in 2.5% while FFLB profiles of unknown species
were detected in 19% of flies examined. This is the first report on molecular
diversity of tsetse flies and their trypanosomes in MZ; all trypanosomes
pathogenic for ungulates were detected, but no human pathogens were detected.
Overall, two species of tsetse flies harbor 12 species/genotypes of trypanosomes.
This notable species richness was likely uncovered because flies were captured in
wildlife reserves and surveyed using the method of FFLB able to identify, with
high sensitivity and accuracy, known and novel trypanosomes. Our findings
importantly improve the knowledge on trypanosome diversity in tsetse flies,
revealed the greatest species richness so far reported in tsetse fly of any
African country, and indicate the existence of a hidden trypanosome diversity to
be discovered in African wildlife protected areas.
PMID- 28688980
TI - Hepatitis E virus seroprevalence rate among Eastern Mediterranean and middle
eastern countries; A systematic review and pooled analysis.
AB - CONTEXT: Hepatitis E virus (HEV) as a hepatotropic virus is one of the major
global health concerns. Autochthonous HEV transmitted by oral fecal-route in poor
sanitation conditions as well as vertical and rarely blood transfusion. HEV
occurrence is more common in developing countries and recently increased in
developed countries too. Middle East (ME) and Eastern Mediterranean region (EMR)
of WHO have been an endemic region for HEV infection. In this regard, we aimed to
design a systematic review and pooled analysis to determine seroprevalence of
anti-HEV antibody in ME and EMR countries. EVIDENCE ACQUISITION: By using PRISMA
guideline, data were collected from papers identified through PubMed, Web of
Science, Science Direct, Scopus and also from some national and regional
databases from January 1990 to June 2016. Serum anti-HEV antibody (IgG) used for
HEV prevalence estimation. HEV prevalence in the ME, WHO EMR countries, and in
total, calculated by each country population size based on 2015 UN report.
RESULTS: overall, 62 papers with a total sample size of 31,673 were fulfilled our
eligibility criteria and included in our project. Considering anti-HEV antibody
(IgG), prevalence of HEV infection in the countries of ME, WHO EMR and in total
were 12.17% (95% CI: 11.79-12.57), 11.81% (95% CI: 11.43-12.21), and 11.87% (95%
CI: 11.52-12.23) respectively. CONCLUSIONS: HEV seroprevalence in WHO EMR and ME
countries has high rate and more considerations are needed for the prevention and
control of this infection especially in high-risk groups such as pregnant women.
PMID- 28688981
TI - Molecular detection of Isoniazid, Rifampin and Ethambutol resistance to M.
tuberculosis and M. bovis in multidrug resistant tuberculosis (MDR-TB) patients
in Pakistan.
AB - The various aspects of MDR-TB, type of pathogen, different drug sensitive methods
and mutation (s) in specific genes were determined. The histone-like protein
(hupB) gene of M. tuberculosis was targeted by using primer sets: N & S and M & S
(produced 645 bp & 318 bp fragment respectively). The most significant risk
factors were the poverty and male gender of ages 11-25 years. All samples were
detected as M. tuberculosis. By Drug Proportion method, the highest percentage
(37%) was found resistant to only Rifampin. By MGIT method, the highest
percentage (82.2%) was found resistant with the triple combination (Rifampin-RIF
+ Isoniazid-INH + Ethambutol-EMB) of the drugs. The highest mutations (76.92%)
were found in gene rpoB (codon 531) in MDR TB patients. By, MAS-PCR, the highest
percentage (34%) were found resistant to combination (INH + RIF) of the drugs.
Minimum samples were resistant to RIF and RIF + INH drugs by MGIT, while
proportionate results were observed from MAS-PCR and DP. Moreover, by MAS-PCR
mutation in gene embB (306) caused EMB resistance (51.64%). We found that M.
tuberculosis was the main cause of MDR-TB. Our findings may further be used for
an early diagnosis of multi-drug resistant tuberculosis.
PMID- 28688982
TI - The effects of striatal silent lacunar infarction on the substantia nigra and
movement disorders in Parkinson's disease: A follow-up study.
AB - OBJECTIVE: Striatal silent lacunar infarction (SSLI) is associated with
structural changes to the substantia nigra (SN), detectable by diffusion kurtosis
imaging (DKI). In this follow-up study, we investigated the effects of SSLI on
the SN and movement disorders in patients with Parkinson's disease (PD). METHODS:
A total of 60 untreated patients with early-stage PD, divided into control and
SSLI groups, were enrolled in this study. All participants underwent conventional
MRI and DKI twice; at baseline and after a 1-year period. We analyzed the
differences of the following variables between the two groups: mean kurtosis (MK)
values of the SN, the severity of disease, daily dosage of levodopa, and the
variation of these indexes from baseline to 1-year visit. Logistic regression
analysis was used to identify the major risk factors for SSLI in PD patients.
RESULTS: 1. All variables showed significant differences between the two groups.
2. The variation in MK values of the SN had a positive correlation with the
variation in the severity of disease. 3. Hypertension and hyperhomocysteinemia
were independent factors for SSLI in patients with PD. CONCLUSION: As PD
progresses, movement disorders become more prominent, with increased structural
changes to the SN, especially in patients with SSLI. Furthermore, PD patients
with hypertension and hyperhomocysteinemia are more likely to have SSLI.
PMID- 28688983
TI - Subjective perception of sleep benefit in Parkinson's disease: Valid or
irrelevant?
AB - INTRODUCTION: The phenomenon of sleep benefit (SB) in Parkinson's disease (PD),
whereby waking motor function is improved despite no dopaminergic treatment
overnight, is controversial. Previous studies suggested a significant discrepancy
between subjective functional and objective motor improvement. The aim of this
study was to determine how well subjective reporting of SB correlates with
objective measures and if true motor improvement can be predicted by a
standardized questionnaire. METHODS: Ninety-two patients with PD participated. A
structured questionnaire was developed to assess subjective SB. Quantitative
motor assessment was performed using a validated smartphone application.
Objective motor SB was considered to be present when the waking motor function
was similar or superior to the daytime on-state. RESULTS: Twenty (22%) patients
showed objective motor improvement on waking compared to end-of-dose. Most
patients (77%) reported subjective SB without corresponding objective motor
benefit. Our structured questionnaire could not predict Motor SB. The ability to
delay morning medications and a perception of indifference or paradoxical
worsening following the morning levodopa dose may suggest Motor SB. CONCLUSIONS:
Most patients experience subjective SB with no measureable motor improvement.
This perceived benefit could be related to non-motor improvement that is
distinctly different to objective motor benefit.
PMID- 28688984
TI - Patient profiling can identify patients with adult spinal deformity (ASD) at risk
for conversion from nonoperative to surgical treatment: initial steps to reduce
ineffective ASD management.
AB - BACKGROUND CONTEXT: Non-operative management is a common initial treatment for
patients with adult spinal deformity (ASD) despite reported superiority of
surgery with regard to outcomes. Ineffective medical care is a large source of
resource drain on the health system. Characterization of patients with ASD likely
to elect for operative treatment from non-operative management may allow for more
efficient patient counseling and cost savings. PURPOSE: This study aimed to
identify deformity and disability characteristics of patients with ASD who
ultimately convert to operative treatment compared with those who remain non
operative and those who initially choose surgery. STUDY DESIGN/SETTING: A
retrospective review was carried out. PATIENT SAMPLE: A total of 510 patients
with ASD (189 non-operative, 321 operative) with minimum 2-year follow-up
comprised the patient sample. OUTCOME MEASURES: Oswestry Disability Index (ODI),
Short-Form 36 Health Assessment (SF-36), Scoliosis Research Society questionnaire
(SRS-22r), and spinopelvic radiographic alignment were the outcome measures.
METHODS: Demographic, radiographic, and patient-reported outcome measures (PROMs)
from a cohort of patients with ASD prospectively enrolled into a multicenter
database were evaluated. Patients were divided into three treatment cohorts: Non
operative (NON=initial non-operative treatment and remained non-operative),
Operative (OP=initial operative treatment), and Crossover (CROSS=initial non
operative treatment with subsequent conversion to operative treatment). NON and
OP groups were propensity score-matched (PSM) to CROSS for baseline demographics
(age, body mass index, Charlson Comorbidity Index). Time to crossover was divided
into early (<1 year) and late (>1 year). Outcome measures were compared across
and within treatment groups at four time points (baseline, 6 weeks, 1 year, and 2
years). RESULTS: Following PSM, 118 patients were included (NON=39, OP=38,
CROSS=41). Crossover rate was 21.7% (41/189). Mean time to crossover was 394
days. All groups had similar baseline sagittal alignment, but CROSS had larger
pelvic incidence and lumbar lordosis (PI-LL) mismatch than NON (11.9 degrees vs.
3.1 degrees , p=.032). CROSS and OP had similar baseline PROM scores; however,
CROSS had worse baseline ODI, PCS, SRS-22r (p<.05). At time of crossover, CROSS
had worse ODI (35.7 vs. 27.8) and SRS Satisfaction (2.6 vs. 3.3) compared with
NON (p<.05). Alignment remained similar for CROSS from baseline to conversion;
however, PROMs (ODI, PCS, SRS Activity/Pain/Total) worsened (p<.05). Early and
late crossover evaluation demonstrated CROSS-early (n=25) had worsening ODI, SRS
Activity/Pain at time of crossover (p<.05). From time of crossover to 2-year
follow-up, CROSS-early had less SRS Appearance/Mental improvement compared with
OP. Both CROSS-early/late had worse baseline, but greater improvements, in ODI,
PCS, SRS Pain/Total compared with NON (p<.05). Baseline alignment and disability
parameters increased crossover odds-Non with Schwab T/L/D curves and ODI>=40
(odds ratio [OR]: 3.05, p=.031), and Non with high PI-LL modifier grades
("+"/'++') and ODI>=40 (OR: 5.57, p=.007) were at increased crossover risk.
CONCLUSIONS: High baseline and increasing disability over time drives conversion
from non-operative to operative ASD care. CROSS patients had similar spinal
deformity but worse PROMs than NON. CROSS achieved similar 2-year outcome scores
as OP. Profiling at first visit for patients at risk of crossover may optimize
physician counseling and cost savings.
PMID- 28688986
TI - Manganese oxide particles as cytoprotective, oxygen generating agents.
AB - : Cell culture and cellular transplant therapies are adversely affected by
oxidative species and radicals. Herein, we present the production of bioactive
manganese oxide nanoparticles for the purpose of radical scavenging and
cytoprotection. Manganese comprises the core active structure of somatic enzymes
that perform the same function, in vivo. Formulated nanoparticles were
characterized structurally and surveyed for maximal activity (superoxide
scavenging, hydrogen peroxide scavenging with resultant oxygen generation) and
minimal cytotoxicity (48-h direct exposure to titrated manganese oxide
concentrations). Cytoprotective capacity was tested using cell exposure to
hydrogen peroxide in the presence or absence of the nanoparticles. Several ideal
compounds were manufactured and utilized that showed complete disproportionation
of superoxide produced by the xanthine/xanthine oxidase reaction. Further, the
nanoparticles showed catalase-like activity by completely converting hydrogen
peroxide into the corresponding concentration of oxygen. Finally, the particles
protected cells (murine beta-cell insulinoma) against insult from hydrogen
peroxide exposure. Based on these observed properties, these particles could be
utilized to combat oxidative stress and inflammatory response in a variety of
cell therapy applications. STATEMENT OF SIGNIFICANCE: Maintaining viability once
cells have been removed from their physiological niche, e.g. culture and
transplant, demands proper control of critical variables such as oxygenation and
removal of harmful substances e.g. reactive oxygen species. Limited catalysts can
transform reactive oxygen species into molecular oxygen and, thereby, have the
potential to maintain cell viability and function. Among these are manganese
oxide particles which are the subject of this study.
PMID- 28688985
TI - Mussel-inspired PLGA/polydopamine core-shell nanoparticle for light induced
cancer thermochemotherapy.
AB - : Most photothermal converting systems are not biodegradable, which bring the
uneasiness when they are administered into human body due to the uncertainty of
their fate. Hereby, we developed a mussel-inspired PLGA/polydopamine core-shell
nanoparticle for cancer photothermal and chemotherapy. With the help of an anti
EGFR antibody, the nanoparticle could effectively enter head and neck cancer
cells and convert near-infrared light to heat to trigger drug release from PLGA
core for chemotherapy as well as ablate tumors by the elevated temperature. Due
to the unique nanoparticle concentration dependent peak working-temperature
nature, an overheating or overburn situation can be easily prevented. Since the
nanoparticle was retained in the tumor tissue and subsequently released its
payload inside the cancer cells, no any doxorubicin-associated side effects were
detected. Thus, the developed mussel-inspired PLGA/polydopamine core-shell
nanoparticle could be a safe and effective tool for the treatment of head and
neck cancer. STATEMENT OF SIGNIFICANCE: The described EGFR targeted
PLGA/polydopamine core-shell nanoparticle (PLGA/PD NP) is novel in the following
aspects: Different from most photothermal converting nanomaterials, PLGA/PD NP is
biodegradable, which eliminates the long-term safety concerns thwarting the
clinical application of photothermal therapy. Different from most photothermal
nanomaterials, upon NIR irradiation, PLGA/PD NP quickly heats its surrounding
environment to a NP concentration dependent peak working temperature and uniquely
keeps that temperature constant through the duration of light irradiation. Due to
this unique property an overheating or overburn situation for the adjacent
healthy tissue can be easily avoided. The PLGA/PD NP releases its payload through
detaching PD shell under NIR laser irradiation. The EGFR-targeted doxorubicin
loaded PLGA/PD NP effectively eradicate head and neck tumor in vivo through the
synergism of photothermal therapy and chemotherapy while not introducing
doxorubicin associated cardiotoxicity.
PMID- 28688987
TI - Tumor targeting by lentiviral vectors combined with magnetic nanoparticles in
mice.
AB - : Nanomaterials conjugated or complexed with biological moieties such as
antibodies, polymers or peptides appear to be suitable not only for drug delivery
but also for specific cancer treatment. Here, biocompatible iron oxide magnetic
nanoparticles (MNPs) with or without a silica shell coupled with lentiviral
vectors (LVs) are proposed as a combined therapeutic approach to specifically
target gene expression in a cancer mouse model. Initially, four different MNPs
were synthesized and their physical properties were characterized to establish
and discriminate their behaviors. MNPs and LVs strictly interacted and transduced
cells in vitro as well as in vivo, with no toxicity or inflammatory responses. By
injecting LV-MNPs complexes intravenously, green fluorescent protein (GFP)
resulted in a sustained long-term expression. Furthermore, by applying a magnetic
field on the abdomen of intravenous injected mice, GFP positive cells increased
in livers and spleens. In liver, LV-MNPs were able to target both hepatocytes and
non-parenchymal cells, while in a mouse model with a grafted tumor, intra-tumor
LV-MNPs injection and magnetic plaque application next to the tumor demonstrated
the efficient uptake of LV-MNPs complexes with high number of transduced cells
and iron accumulation in the tumor site. More important, LV-MNPs with the
application of the magnetic plaque spread in all the tumor parenchyma and
dissemination through the body was prevented confirming the efficient uptake of
LV-MNPs complexes in the tumor. Thus, these LV-MNPs complexes could be used as
multifunctional and efficient tools to selectively induce transgene expression in
solid tumor for therapeutic purposes. STATEMENT OF SIGNIFICANCE: Our study
describes a novel approach of combining magnetic properties of nanomaterials with
gene therapy. Magnetic nanoparticles (MNPs) coated with or without a silica shell
coupled with lentiviral vectors (LVs) were used as vehicle to target biological
active molecules in a mouse cancer model. After in situ injection, the presence
of MNP under the magnetic field improve the vector distribution in the tumor mass
and after systemic administration, the application of the magnetic field favor
targeting of specific organs for LV transduction and specifically can direct LV
in specific cells (or avoiding them). Thus, our findings suggest that LV-MNPs
complexes could be used as multifunctional and efficient tools to selectively
induce transgene expression in solid tumor for therapeutic purposes.
PMID- 28688988
TI - Bactericidal activity of self-assembled palmitic and stearic fatty acid crystals
on highly ordered pyrolytic graphite.
AB - : The wings of insects such as cicadas and dragonflies have been found to possess
nanostructure arrays that are assembled from fatty acids. These arrays can
physically interact with the bacterial cell membranes, leading to the death of
the cell. Such mechanobactericidal surfaces are of significant interest, as they
can kill bacteria without the need for antibacterial chemicals. Here, we report
on the bactericidal effect of two of the main lipid components of the insect wing
epicuticle, palmitic (C16) and stearic (C18) fatty acids. Films of these fatty
acids were re-crystallised on the surface of highly ordered pyrolytic graphite.
It appeared that the presence of two additional CH2 groups in the alkyl chain
resulted in the formation of different surface structures. Scanning electron
microscopy and atomic force microscopy showed that the palmitic acid
microcrystallites were more asymmetric than those of the stearic acid, where the
palmitic acid microcrystallites were observed to be an angular abutment in the
scanning electron micrographs. The principal differences between the two types of
long-chain saturated fatty acid crystallites were the larger density of peaks in
the upper contact plane of the palmitic acid crystallites, as well as their
greater proportion of asymmetrical shapes, in comparison to that of the stearic
acid film. These two parameters might contribute to higher bactericidal activity
on surfaces derived from palmitic acid. Both the palmitic and stearic acid
crystallite surfaces displayed activity against Gram-negative, rod-shaped
Pseudomonas aeruginosa and Gram-positive, spherical Staphylococcus aureus cells.
These microcrystallite interfaces might be a useful tool in the fabrication of
effective bactericidal nanocoatings. STATEMENT OF SIGNIFICANCE: Nanostructured
cicada and dragonfly wing surfaces have been discovered to be able physically
kill bacterial cells. Here, we report on the successful fabrication of
bactericidal three-dimensional structures of two main lipid components of the
epicuticle of insect wings, palmitic (C16) and stearic (C18) acids. After
crystallisation onto highly ordered pyrolytic graphite, both the palmitic and
stearic acid films displayed bactericidal activity against both Gram-negative
Pseudomonas aeruginosa and Gram-positive Staphylococcus aureus cells. The
simplicity of the production of these microcrystallite interfaces suggests that a
fabrication technique, based on solution deposition, could be an effective
technique for the application of bactericidal nanocoatings.
PMID- 28688989
TI - Involvement of oxidative stress and calcium signaling in airborne particulate
matter - induced damages in human pulmonary artery endothelial cells.
AB - Recent studies have revealed that particulate matter (PM) exert deleterious
effects on vascular function. Pulmonary artery endothelial cells (HPAEC), which
are involved in the vasomotricity regulation, can be a direct target of inhaled
particles. Modifications in calcium homeostasis and oxidative stress are critical
events involved in the physiopathology of vascular diseases. The objectives of
this study were to assess the effects of PM2.5 on oxidative stress and calcium
signaling in HPAEC. Different endpoints were studied, (i) intrinsic and
intracellular production of reactive oxygen species (ROS) by the H2DCF-DA probe,
(ii) intrinsic, intracellular and mitochondrial production of superoxide anion
(O2-) by electronic paramagnetic resonance spectroscopy and MitoSOX probe, (iii)
reactive nitrosative species (RNS) production by Griess reaction, and (vi)
calcium signaling by the Fluo-4 probe. In acellular conditions, PM2.5 leads to an
intrinsic free radical production (ROS, O2-) and a 4h-exposure to PM2.5 (5
15MUg/cm2), induced, in HPAEC, an increase of RNS, of global ROS and of
cytoplasmic and mitochondrial O2- levels. The basal intracellular calcium ion
level [Ca2+]i was also increased after 4h-exposure to PM2.5 and a pre-treatment
with superoxide dismutase and catalase significantly reduced this response. This
study provides evidence that the alteration of intracellular calcium homeostasis
induced by PM2.5 is closely correlated to an increase of oxidative stress.
PMID- 28688990
TI - Value of cardiac magnetic resonance imaging and programmed ventricular
stimulation in patients with frequent premature ventricular complexes undergoing
radiofrequency ablation.
AB - BACKGROUND: Frequent premature ventricular complexes (PVCs) have been associated
with increased mortality. However, the optimal approach to the risk
stratification of these patients is unclear. OBJECTIVE: The purpose of this study
was to prospectively assess the use of cardiac magnetic resonance imaging (MRI)
and programmed ventricular stimulation to identify patients with PVCs undergoing
radiofrequency ablation at risk for adverse long-term outcomes. METHODS: A total
of 321 consecutive patients (52 +/- 15 years; 157 men [49%]; left ventricular
ejection fraction 51% +/- 12%) underwent PVC ablation between 2004 and 2015,
preceded by cardiac MRI to assess for structural heart disease (SHD). Programmed
stimulation was performed at the time of the ablation procedure. If ventricular
tachycardia (VT) was induced in the presence of SHD, an implantable cardioverter
defibrillator (ICD) was implanted. RESULTS: SHD was identified by MRI in 64
patients (20%), and sustained monomorphic VT was inducible in 15 patients (5%).
Fourteen patients had both SHD and inducible VT, and received an ICD after the
procedure. The primary endpoint of VT/ventricular fibrillation or death was met
in 15 patients after a median 20 months of follow-up. The combination of SHD by
MRI and VT inducibility conferred independently an increased risk of adverse
outcome (multivariate hazard ratio 25.73, 95% confidence interval 6.74-98.20; P
<.001). CONCLUSION: Preablation cardiac MRI and programmed stimulation can be
useful for risk stratification in patients with frequent PVCs. Patients with
inducible VT in the setting of SHD may benefit from ICD implantation after
ablation regardless of left ventricular ejection fraction.
PMID- 28688991
TI - Triterpenoids from Cyclocarya paliurus and their inhibitory effect on the
secretion of apoliprotein B48 in Caco-2 cells.
AB - Five previously undescribed compounds including two triterpenoid aglycones,
3beta,23-dihydroxy-1,12-dioxo-olean-28-oic acid and 3beta,23,27-trihydroxy-1-oxo
olean-12-ene-28-oic acid, and three triterpenoid glucosides cyclocarioside L-N,
along with 17 known compounds were isolated from a CH3Cl-soluble extract of the
leaves of Cyclocarya paliurus. Two 27-nor-triterpenoid glycosides were isolated
from the genus for the first time. Furthermore, the characterized compounds were
tested for the inhibitory effects on apoliprotein B48 secretion in Caco-2 cells.
Seven triterpenoid aglycones together with four triterpenoid saponins
significantly decreased the apoliprotein B48 oversecretion induced by oleic acid
in Caco-2 cells.
PMID- 28688992
TI - Intramedullary Cervical Spinal Cord Abscess.
AB - Intramedullary spinal cord abscesses are rarely encountered in modern
neurosurgical practice. Select patients are at high risk for developing an
intramedullary spinal cord abscess, which can result in acute neurologic
deficits. Patients with failed conservative management may benefit from early
surgical intervention; however, the evidence is limited by level 3 studies. In
this case presentation, the patient failed conservative management for a cervical
intramedullary spinal cord abscess and developed acute neurologic deficits. The
decision was made to perform an urgent cervical laminectomy and drainage to avoid
any further decline that may have occurred with continued conservative
management. Increased awareness of intramedullary spinal cord abscess is
warranted for its clinical suspicion and emergent treatment in select
circumstances.
PMID- 28688993
TI - Fat, demented and stupid: An unrecognized legacy of pediatric urology?
AB - : The human body is an unfathomably intricate structure consisting of many
connected and intertwined systems. This makes it impossible for therapeutic
interventions to selectively target only one physiologic system without some
impact or side effects on all the other systems. The resiliency of the human body
modifies and disguises side effects, some of which may be undetectable for years
and not apparent without scientific investigation. Pediatric urologists employ
relatively few medications for the common conditions they treat and in general
these consist of antibiotics, anticholinergics, and anesthetics. Although harm
from early side effects is well recognized, recent medical literature suggests
there may be other side effects of these common interventions that aren't as well
recognized. Antibiotics have been added to livestock feed as growth promoters for
three-quarters of a century. Antibiotics alter the microbiota of the intestinal
tract and these alterations have been demonstrated to impact growth, metabolism,
and the risk of obesity in animals and humans. To date, the long-term impact of
daily antibiotic prophylaxis in children with such pediatric urology conditions
as vesicoureteral reflux or prenatal hydronephrosis have not been published.
Similarly, there are no studies assessing long-term effects of anticholinergic
use on cognition in children despite research demonstrating an increased risk of
dementia in adults using anticholinergics. Research in animals and children
recently led the FDA to issue a warning regarding the risk of lengthy use of
general anesthesia on cognitive development in children. CONCLUSIONS: This review
raises the possibility that antibiotics in children may alter growth,
anticholinergics may increase their risk of dementia later in life, and
anesthetics may impair their cognitive development. The possibility of such an
unrecognized legacy from current therapeutic interventions should give all
physicians, including pediatric urologists, pause for consideration before
electing any intervention, no matter how routine or currently well accepted.
PMID- 28688994
TI - Comparison of 30-day emergency department bouncebacks after pediatric versus
adult urologic surgery.
AB - INTRODUCTION: More pediatric patients seem to present to the emergency department
(ED) for non-urgent matters after urologic procedures than adult patients. Under
new and expanding healthcare reform, pediatric urologists may be penalized for
these visits. We compare our 30-day postoperative bounceback rates to the ED and
the acuity of the concerns in these populations. MATERIALS AND METHODS: All
urology consults at our institution are maintained on a prospectively tracked
database. We identified all patients who presented to our adult or pediatric ED
between July 2013 and June 2015 within 30 days of a urologic procedure. We
investigated the patient demographics including age, race, insurance, distance
from the home zip code to the ED, procedures performed, chief complaint in the
ED, diagnosis, and treatment required. RESULTS: In our pediatric group, there
were 67 visits for 56 patients (19 female, 37 male, mean age 6.8 years), which
represents an overall bounceback incidence of 2.7%. Of those, 19% required
admission (0.60% overall readmission rate), 10% underwent a procedure (0.32%
reoperative rate, 18% required catheter manipulation/placement, 13% were given a
prescription (most commonly for constipation), 6% required local wound care, and
33% were reassured only). Most pediatric patients had private insurance (62.5%)
and those with private insurance or who were uninsured tended to require only
reassurance compared to those with Medicare/Medicaid (p = 0.053). In the adult
population, there were 369 visits in 310 patients (111 female, 199 male, mean age
55.4 years) for an incidence of 4.4%. Of those, 42% were admitted (2.2% overall
readmission rate), 14% underwent a procedure (0.74% reoperative rate), 11%
required catheter manipulation/placement, 14% were given medication (most
commonly antibiotics and narcotics), 4% were given local wound care, and 12% were
reassured. Most adult patients had Medicare/Medicaid (48.7%), but insurance type
was not related to treatment required (p = 0.382). On multivariable analysis,
pediatric patients, closer proximity to the hospital, and earlier postoperative
day at presentation to the ED were predictive of requiring only reassurance.
CONCLUSIONS: Compared to adults, pediatric patients are less likely to return to
the ED postoperatively (p < 0.001), but they are significantly more likely to
require only reassurance (p < 0.001) while adults are significantly more likely
to require hospital admission (p < 0.001). In both groups, nearly one-third of
patients required only catheter care or medication. This difference could have
significant implications for new healthcare policy.
PMID- 28688995
TI - Catchment scale assessment of risk posed by traffic generated heavy metals and
polycyclic aromatic hydrocarbons.
AB - Heavy metals (HMs) and polycyclic aromatic hydrocarbons (PAHs) are among the most
toxic chemical pollutants present in urban stormwater. Consequently, urban
stormwater reuse is constrained due to the human health risk posed by these
pollutants. This study developed a scientifically robust approach to assess the
risk to human health posed by HMs and PAHs in urban stormwater in order to
enhance its reuse. Accordingly, an innovative methodology was created consisting
of four stages: quantification of traffic and land use parameters; estimation of
pollutant concentrations for model development; risk assessment, and risk map
presentation. This methodology will contribute to catchment scale assessment of
the risk associated with urban stormwater and for risk mitigation. The risk map
developed provides a simple and efficient approach to identify the critical areas
within a large catchment. The study also found that heavy molecular weight PAHs
(PAHs with 5-6 benzene rings) in urban stormwater pose higher risk to human
health compared to light molecular PAHs (PAHs with 2-4 benzene rings). These
outcomes will facilitate the development of practical approaches for applying
appropriate mitigation measures for the safe management of urban stormwater
pollution and for the identification of enhanced reuse opportunities.
PMID- 28688996
TI - Zika virus dynamics: When does sexual transmission matter?
AB - The Zika virus (ZIKV) has captured worldwide attention with the ongoing epidemic
in South America and its link to severe birth defects, most notably microcephaly.
ZIKV is spread to humans through a combination of vector and sexual transmission,
but the relative contribution of these transmission routes to the overall
epidemic remains largely unknown. Furthermore, a disparity in the reported number
of infections between males and females has been observed. We develop a
mathematical model that describes the transmission dynamics of ZIKV to determine
the processes driving the observed epidemic patterns. Our model reveals a 4.8%
contribution of sexual transmission to the basic reproductive number, R0. This
contribution is too minor to independently sustain an outbreak but suggests that
vector transmission is the main driver of the ongoing epidemic. We also find a
minor, yet statistically significant, difference in the mean number of cases in
males and females, both at the peak of the epidemic and at equilibrium. While
this suggests an intrinsic disparity between males and females, the differences
do not account for the vastly greater number of reported cases for females,
indicative of a large reporting bias. In addition, we identify conditions under
which sexual transmission may play a key role in sparking an epidemic, including
temperate areas where ZIKV mosquito vectors are less prevalent.
PMID- 28688997
TI - Maternal body mass index impacts fetal-placental size at birth and umbilical cord
oxygen values with implications for regulatory mechanisms.
AB - BACKGROUND: Maternal under- and over-nutrition are known to effect fetal growth
with altered placental development and nutrient transport, but whether fetal
oxygenation is also altered remains unknown. AIMS: To examine linkages between
maternal BMI and birth weights, placental weights, and umbilical vein and artery
PO2, with implications for signaling mechanisms. STUDY DESIGN: Population-based
cohort study. SUBJECTS: Analysis of hospital database information on all patients
with pre-pregnant BMI values delivering viable, singleton infants between Jan 1,
1999 and Dec 31, 2010 (N=29,212). BMI was categorized into underweight, normal
weight, overweight, and obese, with birth weights categorized into small (SGA),
appropriate (AGA), and large for gestational age (LGA). OUTCOME MEASURES:
Maternal BMI, birth and placental weights, umbilical vein and artery PO2.
RESULTS: Underweight mothers with smaller infants and overweight/obese mothers
with larger infants had disproportionately large placentas, suggesting
compensatory and/or enhanced placental growth in these pregnancies. All SGA
infants had lower umbilical vein and artery PO2, consistent with aberrant
placental development leading to diffusional impairment of oxygen. Both maternal
overweight/obese BMI and LGA resulted in lower artery PO2, likely due to
increased growth rates with the larger size in these infants. CONCLUSIONS: These
findings support fetal hypoxemia as a common determinant of growth restriction,
whether in underweight mothers and due to under-nutrition or in overweight/obese
mothers and due to placental insufficiency. However, oxygen is unlikely to be the
primary promotor for fetal growth in overweight/obese mothers and LGA infants,
with other substrates of more importance as nutritional cues in these
pregnancies.
PMID- 28688998
TI - Targeted temperature management in the ICU: Guidelines from a French expert
panel.
AB - Over the recent period, the use of induced hypothermia has gained an increasing
interest for critically ill patients, in particular in brain-injured patients.
The term "targeted temperature management" (TTM) has now emerged as the most
appropriate when referring to interventions used to reach and maintain a specific
level temperature for each individual. TTM may be used to prevent fever, to
maintain normothermia, or to lower core temperature. This treatment is widely
used in intensive care units, mostly as a primary neuroprotective method.
Indications are, however, associated with variable levels of evidence based on
inhomogeneous or even contradictory literature. Our aim was to conduct a
systematic analysis of the published data in order to provide guidelines. We
present herein recommendations for the use of TTM in adult and paediatric
critically ill patients developed using the Grading of Recommendations
Assessment, Development, and Evaluation (GRADE) method. These guidelines were
conducted by a group of experts from the French Intensive Care Society (Societe
de reanimation de langue francaise [SRLF]) and the French Society of Anesthesia
and Intensive Care Medicine (Societe francaise d'anesthesie reanimation [SFAR])
with the participation of the French Emergency Medicine Association (Societe
francaise de medecine d'urgence [SFMU]), the French Group for Pediatric Intensive
Care and Emergencies (Groupe francophone de reanimation et urgences pediatriques
[GFRUP]), the French National Association of Neuro-Anesthesiology and Critical
Care (Association nationale de neuro-anesthesie reanimation francaise [ANARLF]),
and the French Neurovascular Society (Societe francaise neurovasculaire [SFNV]).
Fifteen experts and two coordinators agreed to consider questions concerning TTM
and its practical implementation in five clinical situations: cardiac arrest,
traumatic brain injury, stroke, other brain injuries, and shock. This resulted in
30 recommendations: 3 recommendations were strong (Grade 1), 13 were weak (Grade
2), and 14 were experts' opinions. After two rounds of rating and various
amendments, a strong agreement from voting participants was obtained for all 30
(100%) recommendations, which are exposed in the present article.
PMID- 28688999
TI - Assessing the implementation of a bedside service handoff on an academic
hospitalist service.
AB - BACKGROUND: Inpatient service handoffs are a vulnerable transition during a
patients' hospitalization. We hypothesized that performing the service handoff at
the patients' bedside may be one mechanism to more efficiently transfer patient
information between physicians, while further integrating the patient into their
hospital care. METHODS: We performed a 6-month prospective study of performing a
bedside handoff (BHO) at the service transition on a non-teaching hospitalist
service. On a weekly basis, transitioning hospitalists co-rounded at patient's
bedsides. Post-handoff surveys assessed for completeness of handoff,
communication, missed information, and adverse events. A control group who
performed the handoff via email, phone or face-to-face was also surveyed. Chi
square and item-response theory (IRT) analysis assessed for differences between
BHO and control groups. Narrative responses were elicited to qualitatively
describe the BHO. RESULTS: In total, 21/31 (67%) scheduled BHOs were performed.
On average, 4 out of 6 eligible patients experienced a BHO, with a total of 90
patients experiencing a BHO. Of those asked to perform the BHO, 52% stated the
service transition took 31-60 min compared to 24% in the control group.
Controlling for the nesting of observations within physicians, IRT analysis found
that BHO respondents had statistically significant greater odds of: reporting
increased patient awareness of the service handoff, more certainty in the plan
for each patient, less discovery of missed information, and less time needed to
learn about the patient on the first day compared to control methods. Narrative
responses described a more patient-centered handoff with improved communication
that was time-consuming and often logistically difficult to implement.
CONCLUSIONS: Despite its time-intensive nature, performing the service handoff at
the patient's bedside may lead to a more complete and efficient service
transition.
PMID- 28689000
TI - Morphological and physiological characteristics of a virulent and zoonotic
assemblage A Giardia duodenalis canine strain.
AB - Giardiasis is an intestinal parasitosis that affects millions of people worldwide
and is considered a zoonotic disease. Frequently in contact with humans, dogs are
the main host involved in this zoonotic transmission. Here, we compared some
aspects of Giardia duodenalis biology between two strains: a recently isolated
dog strain (BHFC1) and a human reference strain (Portland-1). Growth curve
analysis revealed that BHFC1 trophozoites multiply faster than the human isolate
Portland-1 in axenic culture, but has a lower rate of cysts formation. Scanning
electron microscopy revealed that BHFC1 trophozoites have the same conventional
shape and morphological structures expected for G. duodenalis trophozoites, but
presented a more prominent flange. For the best of our knowledge, this work is
the first description of morphological aspects and encystation process of a G.
duodenalis strain isolated from a dog. Since BHFC1 and Portland-1 have been
maintained in axenic cultures for different periods of time, differences observed
in growth, encystation rates and flange size may be attributed to adaptation of
Portland-1 to axenic culture and lack of the environmental pressures. BHFC1 can
be useful as tool for better understanding of Giardia duodenalis biology.
PMID- 28689001
TI - Immuno-oncologic Approaches: CAR-T Cells and Checkpoint Inhibitors.
AB - Advances in understanding myeloma biology have shown that disease progression is
not only the consequence of intrinsic tumor changes but also of interactions
between the tumor and the microenvironment in which the cancer grows. The immune
system is an important component of the tumor microenvironment in myeloma, and
acting on the immune system is an appealing new treatment strategy. There are 2
ways to act toward immune cells and boost antitumor immunity: (1) to increase
antitumor activity (acting on T and NK cytotoxic cells), and (2) to reduce
immunosuppression (acting on myeloid-derived stem cells and T regulatory cells).
Checkpoint inhibitors and adoptive cell therapy (ACT) are 2 of the main actors,
together with monoclonal antibodies and immunomodulatory agents, in the immune
oncologic approach. The aim of checkpoint inhibitors is to release the brakes
that block the action of the immune system against the tumor. Anti-programmed
death-1 (PD-1) and PD-1-Ligand, as well as anti-CTLA4 and KIR are currently under
evaluation, as single agents or in combination, with the best results achieved so
far with combination of anti-PD-1 and immunomodulatory agents. The aim of ACT is
to create an immune effector specific against the tumor. Preliminary results on
chimeric antigen receptor (CAR) T cells, first against CD19, and more recently
against B-cell maturation antigen, have shown to induce durable responses in
heavily pretreated patients. This review focuses on the most recent clinical
results available on the use of checkpoint inhibitors and CAR-T cells in myeloma,
in the context of the new immune-oncologic approach.
PMID- 28689002
TI - Age Acts as an Adverse Independent Variable for Survival in Acute Lymphoblastic
Leukemia: Data From a Cohort in Northeast Mexico.
AB - BACKGROUND: Survival for acute lymphoblastic leukemia (ALL) decreases with age.
Patients across all age groups from a homogeneous ethnic and socioeconomic
background were studied to document age effect. MATERIAL AND METHODS: Patients
diagnosed from 2005 to 2015 at a university hospital in Northeast Mexico were
divided into 4 age groups: infants (< 1), children (>= 1 to < 16), adolescents
(>= 16 to <= 20), and adults (> 20 years). Correlation between age at diagnosis
and relapse-free (RFS) and overall survival (OS) was investigated. RESULTS: A
total of 377 patients were included. Five-year RFS and OS for children were 55.6%
and 66.9%; for adolescents, 36.0% and 48.3%; for adults, 19.5% and 24.1%,
respectively. Differences in RFS and OS between age groups were significant (P <
.001, P < .001). In the Cox regression model, all age groups reached statistical
significance in univariate analysis of mortality. CONCLUSION: Age plays a
decisive role in clinical evolution of ALL and strongly influences outcome. Age
older than 20 represents a progressive high-risk factor for death.
PMID- 28689003
TI - Primary Amyloidosis With Renal Involvement: Outcomes in 77 Consecutive Patients
at a Single Center.
AB - BACKGROUND: Outcomes in primary amyloid renal patients are of interest as the era
of monoclonal antibody therapies begins. PATIENTS AND METHODS: We studied 77
consecutive primary amyloid renal patients (58% men) for renal progression (end
stage renal disease [ESRD]), renal response (RR), and overall survival (OS).
RESULTS: At diagnosis median age was 63 (range, 35-81) years, estimated
glomerular filtration rate 70 mL/min (range, 5-114), difference between involved
and uninvolved free light chains 127 mg/L (range, 1-9957), ESRD 4%, renal stage 2
and 3 78%, and cardiac stage 2 and 3 56%. Ninety-six percent received bortezomib
and 44% stem cell transplantation as well as bortezomib, 68% achieved complete or
very good partial hematologic response (CR/VGPR), 34% had ESRD, and 39% RR.
Median times to ESRD and RR were 18 (range, 3-81) and 12 (range, 2-30) months,
respectively. Median OS was not reached in this cohort and was not reached from
onset of ESRD. More than two-thirds of patients with ESRD also achieved CR/VGPR.
In those without ESRD at diagnosis, baseline creatinine and absent RR predicted
progression to ESRD in multivariate Cox regression analysis, whereas CR/VGPR
predicted RR. In multivariate Cox regression analysis, cardiac stage and
achievement of CR/VGPR predicted OS, enabling construction of a prognostic model.
CONCLUSION: Anti-plasma cell therapies provide a definite albeit limited benefit
and new approaches to amyloid-related organ dysfunction are needed.
PMID- 28689005
TI - Neuregulin-1beta as a potential therapeutic for targeting fibroblasts in heart
disease.
PMID- 28689006
TI - Interactions between pro-inflammatory cytokines and statins on depression in
patients with acute coronary syndrome.
AB - OBJECTIVE: Pro-inflammatory cytokines are associated with the development of
depression and statins exert anti-inflammatory and antidepressant effects. The
present study aimed to investigate associations between interleukin (IL)-6 and IL
18 and depression in patients with acute coronary syndrome (ACS) and potential
interactions between statin use and pro-inflammatory cytokines on depression in
this population. METHODS: We used pooled datasets from 1-year follow-up data from
a 24-week randomized double-blind placebo-controlled trial (RCT) of escitalopram
for treatment of depressive disorder and data from a naturalistic, prospective,
observational cohort study in patients with ACS. IL-6 and IL-18 levels were
measured at baseline. Logistic regression models were used to investigate
independent associations of IL-6/IL-18 levels with depressive disorder at
baseline and at 1year. We repeated all analyses by reference to statin use to
determine whether any significant association emerged. RESULTS: Of the 969
participants, 378 (39.0%) had major or minor depression at baseline. Of 711
patients followed-up at 1year, 183 (25.7%) had depression. Logistic regression
analysis showed that higher IL-6 and IL-18 levels at baseline were significantly
associated with baseline depression after adjusting for other variables (adjusted
p-values=0.005 and 0.001, respectively). IL-6 and IL-18 levels were also
significantly higher in patients with depression at the 1-year follow-up after
adjusting for other variables amongst those not taking statins (adjusted p
values=0.040 and 0.004, respectively); but this was not the case in patients
taking statins. CONCLUSION: Levels of pro-inflammatory cytokines appear to
predict development of depression after ACS and statins attenuate the effects of
cytokines on depression.
PMID- 28689007
TI - Creativity and psychiatric illness: A functional perspective beyond chaos.
PMID- 28689008
TI - Amygdala functional disconnection with the prefrontal-cingulate-temporal circuit
in chronic tinnitus patients with depressive mood.
AB - Chronic tinnitus is often accompanied with depressive symptom, which may arise
from aberrant functional coupling between the amygdala and cerebral cortex. To
explore this hypothesis, resting-state functional magnetic resonance imaging
(fMRI) was used to investigate the disrupted amygdala-cortical functional
connectivity (FC) in chronic tinnitus patients with depressive mood. Chronic
tinnitus patients with depressive mood (n=20), without depressive mood (n=20),
and well-matched healthy controls (n=23) underwent resting-state fMRI scanning.
Amygdala-cortical FC was characterized using a seed-based whole-brain correlation
method. The bilateral amygdala FC was compared among the three groups. Compared
to non-depressed patients, depressive tinnitus patients showed decreased amygdala
FC with the prefrontal cortex and anterior cingulate cortex as well as increased
amygdala FC with the postcentral gyrus and lingual gyrus. Relative to healthy
controls, depressive tinnitus patients revealed decreased amygdala FC with the
superior and middle temporal gyrus, anterior and posterior cingulate cortex, and
prefrontal cortex, as well as increased amygdala FC with the postcentral gyrus
and lingual gyrus. The current study identified for the first time abnormal
resting-state amygdala-cortical FC with the prefrontal-cingulate-temporal circuit
in chronic tinnitus patients with depressive mood, which will provide novel
insight into the underlying neuropathological mechanisms of tinnitus-induced
depressive disorder.
PMID- 28689004
TI - The role of succinate and ROS in reperfusion injury - A critical appraisal.
AB - We critically assess the proposal that succinate-fuelled reverse electron flow
(REF) drives mitochondrial matrix superoxide production from Complex I early in
reperfusion, thus acting as a key mediator of ischemia/reperfusion (IR) injury.
Real-time surface fluorescence measurements of NAD(P)H and flavoprotein redox
state suggest that conditions are unfavourable for REF during early reperfusion.
Furthermore, rapid loss of succinate accumulated during ischemia can be explained
by its efflux rather than oxidation. Moreover, succinate accumulation during
ischemia is not attenuated by ischemic preconditioning (IP) despite powerful
cardioprotection. In addition, measurement of intracellular reactive oxygen
species (ROS) during reperfusion using surface fluorescence and mitochondrial
aconitase activity detected major increases in ROS only after mitochondrial
permeability transition pore (mPTP) opening was first detected. We conclude that
mPTP opening is probably triggered initially by factors other than ROS, including
increased mitochondrial [Ca2+]. However, IP only attenuates [Ca2+] increases
later in reperfusion, again after initial mPTP opening, implying that IP
regulates mPTP opening through additional mechanisms. One such is mitochondria
bound hexokinase 2 (HK2) which dissociates from mitochondria during ischemia in
control hearts but not those subject to IP. Indeed, there is a strong correlation
between the extent of HK2 loss from mitochondria during ischemia and infarct size
on subsequent reperfusion. Mechanisms linking HK2 dissociation to mPTP
sensitisation remain to be fully established but several related processes have
been implicated including VDAC1 oligomerisation, the stability of contact sites
between the inner and outer membranes, cristae morphology, Bcl-2 family members
and mitochondrial fission proteins such as Drp1.
PMID- 28689010
TI - The walking bugs.
PMID- 28689009
TI - Survival of Mycobacterium tuberculosis and Mycobacterium bovis BCG in lysosomes
in vivo.
AB - Mycobacterium tuberculosis is one of the most successful pathogens known, having
infected more than a third of the global population. An important strategy for
intracellular survival of pathogenic mycobacteria relies on their capacity to
resist delivery to lysosomes, instead surviving within macrophage phagosomes.
Several factors of both mycobacterial and host origin have been implicated in
this process. However, whether or not this strategy is employed in vivo is not
clear. Here we show that in vivo, following intravenous infection, M.
tuberculosis and Mycobacterium bovis BCG initially survived by resisting
lysosomal transfer. However, after prolonged infection the bacteria were
transferred to lysosomes yet continued to proliferate. A M. bovis BCG mutant
lacking protein kinase G (PknG), that cannot avoid lysosomal transfer and is
readily cleared in vitro, was found to survive and proliferate in vivo. The
ability to survive and proliferate in lysosomal organelles in vivo was found to
be due to an altered host environment rather than changes in the inherent ability
of the bacteria to arrest phagosome maturation. Thus, within an infected host,
both M. tuberculosis and M. bovis BCG adapts to infection-specific host
responses. These results are important to understand the pathology of
tuberculosis and may have implications for the development of effective
strategies to combat tuberculosis.
PMID- 28689011
TI - Coexistence of Ductal Carcinoma Within Mammary Phyllodes Tumor: A Review of 557
Cases From a 20-year Region-wide Database in Hong Kong and Southern China.
AB - INTRODUCTION: Phyllodes tumor (PT) is an uncommon fibroepithelial tumor of the
breast showing predominately proliferation of the stromal component. The presence
of ductal carcinoma in situ (DCIS) or invasive ductal carcinoma is rare, with
only a few cases reported in the literature. METHODS: A retrospective review of a
prospectively maintained database was performed. Patients who were treated for PT
in 5 hospitals in Hong Kong and Shenzhen, China over a period of 20 years (1997
2016) were evaluated. All pathology slides were reported by specialist
pathologists. Patients with coexisting ductal carcinoma were identified. RESULTS:
A total of 557 patients were included in this cohort; 363 (65.2%) patients had
benign PT, 130 (23.3%) had borderline PT, and 64 (11.5%) had malignant PT. There
were 6 (1.1%) patients with coexisting ductal carcinoma in the PT; 5 were DCIS
and 1 was invasive ductal carcinoma. The median age was 46.5 years (range, 25-54
years). Ductal carcinoma occurred more frequently in malignant PT than in benign
or borderline PT (4.7% vs. 0.6%; P = .02). However, malignant PT was not
associated with higher DCIS grade (P = .1). All patients underwent surgery with
clear resection margins. After a median follow-up interval of 70 months (range, 2
101 months), all patients remained disease- and recurrence-free. CONCLUSION: We
report 6 additional uncommon cases of ductal carcinoma complicating PT. The
presence of ductal carcinoma was not adverse prognosticator as these are usually
incidental and situated within the harboring PT.
PMID- 28689012
TI - Locoregional Treatment of the Primary Tumor in Patients With De Novo Stage IV
Breast Cancer: A Radiation Oncologist's Perspective.
AB - BACKGROUND: The aim of this study was to assess the outcomes of patients with de
novo stage IV breast cancer after locoregional treatment (LRT) of primary site.
PATIENTS AND METHODS: We studied 245 patients diagnosed with de novo stage IV
breast cancer. LRT of the primary tumor (+ systemic therapy) was performed in 82
(34%) patients (surgery, 27; surgery + radiotherapy (RT), 46; and RT, 9). Among
those undergoing surgery, 64 (88%) patients underwent mastectomy, and 9 (12%)
patients underwent breast-conserving surgery (BCS). Local recurrence-free
survival (LRFS) and overall survival (OS) were investigated, and propensity score
matching was used to balance patient distributions. RESULTS: The 5-year LRFS and
OS rates were 27% and 50%, respectively. Advanced T stage (T4), liver or brain
metastasis, >= 5 metastatic sites, and absence of hormone therapy were
significant adverse factors for LRFS, whereas T4 stage and absence of hormone
therapy were significant for OS. The LRT group demonstrated significantly more
favorable outcomes (5-year LRFS, 61%; 5-year OS, 71%), especially after surgery.
After matching, survival rates remained significantly higher for patients who
received LRT (5-year LRFS, 62% vs. 20%; P < .001; 5-year OS, 73% vs. 45%; P =
.02). BCS + RT was superior to mastectomy +/- RT, which can be attributed to more
patients with a low tumor burden undergoing BCS + RT. Outcomes were better with
post-mastectomy RT in selected patients (>= N2, >= T3, or T2N1). CONCLUSIONS:
Upfront LRT including RT is an important option together with systemic therapies
for de novo stage IV breast cancer.
PMID- 28689013
TI - Complete genome sequence of Stenotrophomonas sp. KCTC 12332, a biotechnological
potential bacterium.
AB - Hydroxy fatty acids are used in various industries due to their availability, and
in particular, Stenotrophomonas sp. has been regarded as a potential candidate
for biotechnological applications, including biotransformation that hydrate
unsaturated fatty acids into their derivatives. Here we complete the genome
sequence of Stenotrophomonas sp. KCTC 12332 which has a size of 4,541,594bp (G+C
content of 63.83%) with 3790 coding DNA sequences (CDSs), 67 tRNA and 3 rRNA
operons. The genome contains gene encoding oleate hydratase that can convert
oleic acid into 10-hydroxyoctadecanoic acid.
PMID- 28689014
TI - Poly-pathway model, a novel approach to simulate multiple metabolic states by
reaction network-based model - Application to amino acid depletion in CHO cell
culture.
AB - Mammalian cell lines are characterized by a complex and flexible metabolism. A
single model that could describe the variations in metabolic behavior triggered
by variations in the culture conditions would be a precious tool in bioprocess
development. In this paper, we introduce an approach to generate a poly-pathway
model and use it to simulate diverse metabolic states triggered in response to
removal, reduction or doubling of amino acids in the culture medium of an
antibody-producing CHO cell line. Macro-reactions were obtained from a metabolic
network via elementary flux mode enumeration and the fluxes were modeled by
kinetic equations with saturation and inhibition effects from external medium
components. Importantly, one set of kinetic parameters was estimated using
experimental data of the multiple metabolic states. A good fit between the model
and the data was obtained for the majority of the metabolites and the
experimentally observed flux variations. We find that the poly-pathway modeling
approach is promising for the simulation of multiple metabolic states.
PMID- 28689015
TI - The laminin-derived peptide C16 regulates GPNMB expression and function in breast
cancer.
AB - Breast cancer is an important public health problem, and its progression may be
related to the extracellular matrix (ECM), which acts as a structural scaffold
and instruction source for neoplastic cells. Laminins are ECM proteins regulating
tumor biology. The laminin-derived peptide C16 regulates different properties of
tumor cells. Here we analyzed C16-induced differential gene expression in MDA-MB
231 breast cancer cells. MCF-10A normal-like breast cells served as control.
Among different cancer-related genes, C16 induced overexpression of GPNMB. This
gene encodes a transmembrane protein GPNMB (glycoprotein non-metastatic B),
involved with malignant phenotype of breast cancer cells. Immunoblot validated
microarray results. To correlate gene and protein expression with cellular
function, we investigated whether C16 would regulate invasion in breast cancer
cells. siRNA experiments strongly suggested that C16 and GPNMB cooperate to
regulate invasion of highly aggressive MDA-MB-231 cancer cells. We addressed
regulatory mechanisms involved in C16-mediated increase of GPNMB protein levels
in MDA-MB-231 cells, and observed that C16 stimulates beta1 integrin and Src
phosphorylation. Furthermore, Src inhibition decreases peptide-induced GPNMB
expression levels. To contextualize in vivo our results in vitro, we addressed
GPNMB immunostaining in breast cancer human tissue microarrays. Quantitative
immunohistochemistry showed that GPNMB is significantly more expressed in breast
cancer compared to normal tissue. We concluded that laminin-derived peptide C16
regulates gene and protein expression of GPNMB in breast cancer cells. C16 and
GPNMB may cooperate to regulate invasion of highly aggressive MDA-MB-231 cells,
probably through Src signaling. GPNMB presented increased expression in breast
cancer in vivo compared to normal breast tissue.
PMID- 28689016
TI - Long-term follow up of invasive aspergillosis in allogeneic stem cell
transplantation recipients and leukemia patients: Differences in risk factors and
outcomes.
AB - Antifungal prophylaxis (AP) has dramatically changed the epidemiology of invasive
aspergillosis (IA). To better understand the differences in terms of clinical
significance of IA between allogeneic stem cell transplantation (allo-SCT)
recipients and patients treated for leukemia, we report a single-center study of
735 unselected consecutive patients treated between 2000 and 2004, before the era
of systematic AP. Probable or confirmed IA were observed in 29 patients (2008
EORTC/MSG criteria), including 7/235 undergoing allo-SCT (5.2%), 19/380 treated
for acute leukemia (5.0%), 1/116 for chronic lymphocytic leukemia (0.9%) and
2/104 for myelodysplastic syndrome (1.9%). In allo-SCT recipients, IA occurred
later than in leukemia patients, after the neutropenic period. The median time
between the last treatment and the diagnosis of IA was 231 days (range, 68-341)
in allo-SCT recipients and 17 days (6-57) in leukemia patients (P<0.001).
Importantly, the 7 cases of IA after allo- SCT occurred only in patients treated
with corticosteroids for graft-versus-host disease (GVHD). Mortality directly
related to IA was 24%. The 100-day, 2-year and 10-year overall survival were
42.9%, 0%, 0% in allo-SCT recipients compared to 68.1%, 18.2%, 13.6% in leukemia
patients, respectively (P>=0.05). These poor outcomes were mainly attributable to
non-relapse mortality (NRM). In conclusion, our data allows distinguishing 2
types of IA occurring at different time in the treatment course. In both cases,
the NRM is very high and treatment remains challenging. Thus, systematic broad
spectrum AP against Aspergillus should be considered in acute leukemia patients
during the neutropenic phase and in all patients undergoing allo-SCT who develop
GVHD.
PMID- 28689017
TI - Parathyroid hormone-related peptide (1-34) reduces alveolar bone loss in type 1
diabetic rats.
AB - OBJECTIVE: To investigate the role of parathyroid hormone related protein (PTHrP)
in diabetic periodontitis. METHODS: After injected with 55mg/kg streptozotocin,
diabetic rats were treated subcutaneously with low-dose (40MUg/kg, once daily for
5days per week), middle-dose (80MUg/kg) or high-dose (160MUg/kg) PTHrP(1-34)
peptide. Treatment continued for 12 weeks. Changes in periodontal tissues were
confirmed by micro-computerized tomography assay and H&E analysis. We used
tartrate resistant acid phosphatase (TRAP) staining to identify osteoclast cells.
The expression of TNF-alpha, IL-1beta and IL-6 was assessed by
immunohistochemistry and Western blot. RESULTS: Tooth-supporting structure loss
was observed in periodontal tissues of diabetic rats. PTHrP (1-34) attenuated
alveolar bone loss, especially in the middle-dose and high-dose group. Whereas
TNF-alpha, IL-1beta and IL-6 protein levels were increased in the diabetic
gingival tissues, PTHrP (1-34) treatment inhibited the increase of IL-1beta and
IL-6, but had no effect on TNF-alpha. CONCLUSION: Type 1 diabetes increased the
susceptibility to periodontal disease. Intermittent administration of PTHrP (1
34) exhibited an inhibitory effect on alveolar bone resorption and the gingival
inflammation in periodontal tissues of diabetic rats.
PMID- 28689018
TI - Optimizing concentration of titanium tetrafluoride solution for human dentine
remineralization.
AB - OBJECTIVE: The aim of the present study was to select the optimal concentration
of TiF4 solution to facilitate the remineralization of early dentine caries
lesions. DESIGN: Sixty human dentine specimens were cut and randomly divided into
6 groups (1%, 2%, 3%, 4% TiF4 groups, 2.712% NaF group and distilled deionized
water (DDW) control group). Artificial dentine caries-like lesions were created.
After being subjected to fluoride treatment and immersed in remineralizing
solution for 2weeks, the specimens were observed by microCT, scanning electron
microscopy (SEM) and X-ray photoelectron spectroscopy (XPS). Data were analysed
using linear regression analysis (P<0.05). RESULTS: The lesion depths of the
specimens treated by 2% TiF4 solution were statistically less than those of the
other groups. Further, the greyscale values of these lesion areas were greater.
The 3% and 4% TiF4 solutions caused further lesion demineralization. The 2.712%
NaF solution seemed to be detrimental to remineralization during the experimental
time, as the subsurface area remained hypomineralized with a thick precipitation
layer on the surface. CONCLUSIONS: The 2% TiF4 solution demonstrated better
remineralizing potency than did the other treatments.
PMID- 28689019
TI - Common versus specific factors in psychotherapy: opening the black box.
AB - Do psychotherapies work primarily through the specific factors described in
treatment manuals, or do they work through common factors? In attempting to
unpack this ongoing debate between specific and common factors, we highlight
limitations in the existing evidence base and the power battles and competing
paradigms that influence the literature. The dichotomy is much less than it might
first appear. Most specific factor theorists now concede that common factors have
importance, whereas the common factor theorists produce increasingly tight
definitions of bona fide therapy. Although specific factors might have been
overplayed in psychotherapy research, some are effective for particular
conditions. We argue that continuing to espouse common factors with little
evidence or endless head-to-head comparative studies of different psychotherapies
will not move the field forward. Rather than continuing the debate, research
needs to encompass new psychotherapies such as e-therapies, transdiagnostic
treatments, psychotherapy component studies, and findings from neurobiology to
elucidate the effective process components of psychotherapy.
PMID- 28689020
TI - Ferulic acid supresses Th2 immune response and prevents remodeling in ovalbumin
induced pulmonary allergy associated with inhibition of epithelial-derived
cytokines.
AB - : Asthma is characterized by intermittent airway obstruction and chronic
inflammation, orchestrated primarily by Th2 cytokines. There is a strong
rationale for developing new asthma therapies, since current treatment protocols
present side effects and may not be effective in cases of difficult-to-control
asthma. The purpose of this study was to evaluate the effect of ferulic acid, a
phenolic acid commonly present in plants, in the ovalbumin-induced pulmonary
allergy murine model. METHODS: BALB/c mice were sensitized and challenged with
ovalbumin, and treatments were provided by gavage. Six groups of mice (n = 6)
were studied, labeled as: control, pulmonary allergy, dexamethasone, and 3
receiving ferulic acid (at 25, 50, and 100 mg/kg). Lung tissue, bronchoalveolar
lavage fluid and serum were collected for analysis. RESULTS: Ferulic acid
treatment inhibited an established allergic Th2-response by decreasing the key
features of pulmonary allergy, including lung and airway inflammation, eosinophil
infiltration, mucus production and serum levels of OVA-specific IgE. These
results were associated with lower levels of CCL20, CCL11 and CCL5 chemokines and
IL-4, IL-5, IL-13, TSLP, IL-25 and IL-33 cytokines in lung tissue homogenate.
CONCLUSIONS: In this study it was demonstrated for the first time that ferulic
acid treatment is able to suppress one of the main features of the airway
remodeling, indicated by reduction of mucus production, besides the Th2
pathogenic response on ovalbumin-induced pulmonary allergy. Taken together,
results shows that the immunopathological mechanism underlying these effects is
linked to a reduction of the epithelial-derived chemokines and cytokines,
suggesting that ferulic acid may be useful as a potential therapeutic agent for
asthma.
PMID- 28689021
TI - From theory to application: using performance measures for contraceptive care in
the Title X family planning program.
AB - OBJECTIVE: The objective was to describe a Performance Measure Learning
Collaborative (PMLC) designed to help Title X family planning grantees use new
clinical performance measures for contraceptive care. STUDY DESIGN: Twelve Title
X grantee-service site teams participated in an 8-month PMLC from November 2015
to June 2016; baseline was assessed in October 2015. Each team documented their
selected best practices and strategies to improve performance, and calculated the
contraceptive care performance measures at baseline and for each of the
subsequent 8 months. RESULTS: PMLC sites implemented a mix of best practices: (a)
ensuring access to a broad range of methods (n=7 sites), (b) supporting women
through client-centered counseling and reproductive life planning (n=8 sites),
(c) developing systems for same-day provision of all methods (n=10 sites) and (d)
utilizing diverse payment options to reduce cost as a barrier (n=4 sites). Ten
sites (83%) observed an increase in the clinical performance measures focused on
most and moderately effective methods (MME), with a median percent change of 6%
for MME (from a median of 73% at baseline to 77% post-PMLC). CONCLUSION: Evidence
suggests that the PMLC model is an approach that can be used to improve the
quality of contraceptive care offered to clients in some settings. Further
replication of the PMLC among other groups and beyond the Title X network will
help strengthen the current model through lessons learned. IMPLICATIONS: Using
the performance measures in the context of a learning collaborative may be a
useful strategy for other programs (e.g., Federally Qualified Health Centers,
Medicaid, private health plans) that provide contraceptive care. Expanded use of
the measures may help increase access to contraceptive care to achieve national
goals for family planning.
PMID- 28689022
TI - Ultrasonic study of elastic creep in piezoceramics.
AB - Ultrasonic method and experimental setup for study the elastic creep of
piezoelectric materials are described. The results of experimental studies of
time behavior of the Young's modulus and the internal friction are presented as
well as the longitudinal and transversal piezomoduli and the electromechanical
coupling factor. Four compositions of piezoelectric ceramics both soft and hard,
based on BaTiO3 and PZT, were compressed for a long time (0/107s) by significant
static loads (0/120MPa). The possible physical mechanisms that cause the creep
are briefly considered. The concept of a spectrum of activation energies of the
corresponding processes is introduced. The upper and the lower boundaries of the
relaxation times spectrum were measured and corresponding activation energies
were found.
PMID- 28689023
TI - Profiling of cytokines, chemokines and other soluble proteins as a potential
biomarker in colorectal cancer and polyps.
AB - Soluble proteins including cytokines, chemokines and growth factors are small
proteins that mediate and regulate immunity. They involved in the pathogenesis of
many diseases including cancers. The concentration of these proteins in
biological fluids (serum or plasma) and tissues in diseases may suggest pathway
activation that leads to inflammatory response or disease progression. Therefore,
these soluble proteins may be useful as a tool for screening, diagnosis
classification between stages of disease or surveillance for therapy. Enzyme
linked immunosorbent assays (ELISA) and bioassay have been used as a gold
standard in cytokine level measurements in clinical practice. However, these
methods allow only single cytokine detection at a time and ineffective for
screening purposes. Hence, the innovation of multiplexing technology allows
measurement of many these soluble proteins simultaneously, thus allowing rapid,
cost effective and better efficiency by using a minute amount of sample. In this
study, we explored the profiles of key inflammatory cytokines, chemokines and
other soluble proteins from the serum derived from colorectal carcinoma (CRC,
n=20), colorectal polyps (P, n=20) and healthy volunteers (N, n=20) using
multiplexed bead-based immunoassays. We aimed to evaluate if the levels of these
soluble proteins can classify these groups of populations and explore the
possible application of the soluble proteins as biomarkers in early stage
screening and/or surveillance. We observed significant high IL-4, MIP-1beta, FasL
and TGF-beta1 levels but lower levels for RANTES in P-derived serum as compared
to N-derived serum. Significant high IL-8, VEGF, MIP-1beta, Eotaxin and G-CSF
observed in CRC-derived serum when compared to N-derived serum. Between CRC- and
P-derived serum, significantly higher levels of IL-8, Eotaxin and G-CSF but lower
levels for TGF-beta1 were detected in CRC-derived serum. These preliminary
results were obtained from small sample size and could be further validated with
larger sample size cohort to produce a panel of biomarkers for CRC and P
patients. Our findings might be useful in developing a disease-specific panel for
biomarker screening assay. This could be used for early diagnosis and/or
treatment surveillance.
PMID- 28689024
TI - A high fat breakfast attenuates the suppression of appetite and acylated ghrelin
during exercise at simulated altitude.
AB - High-altitude exposure induces a negative energy balance by increasing resting
energy expenditure and decreasing energy intake. This diminished energy intake is
likely caused by altitude-induced anorexia and can have detrimental effects for
those travelling to high-altitude. We aimed to investigate whether altering the
macronutrient composition of breakfast could attenuate altitude-induced anorexia
and augment energy intake at high-altitude. Twelve healthy men (aged 26 (8)
years, body mass index 23.9 (2.7) kg.m-2) completed two, 305min experimental
trials at 4300m simulated altitude (~11.7% O2). After an overnight fast,
participants entered a normobaric hypoxic chamber and rested for one hour, before
receiving either a high fat (HF; 60% fat, 25% carbohydrate) or an isocaloric high
carbohydrate (HC; 60% carbohydrate, 25% fat) breakfast. One hour after breakfast,
participants performed 60min of treadmill walking at 50% of relative VO2max. An
ad-libitum buffet meal was consumed 1h 30min after exercise. Appetite
perceptions, blood samples and substrate oxidation rates were measured
throughout. A significantly higher area under the curve for composite appetite
score was observed during exercise in HF (40 (12) mm.h-1) compared with HC (30
(17) mm.h-1, P=0.036). During exercise, lower insulin concentrations (P=0.013)
and elevated acylated ghrelin concentrations (P=0.048) were observed in HF
compared with HC. After exercise there was no significant difference in composite
appetite score (P=0.356), acylated ghrelin (P=0.229) or insulin (P=0.513) between
conditions. Energy intake at the buffet did not significantly differ between
conditions (P=0.384). A HF breakfast attenuated appetite suppression during
exercise at 4300m simulated altitude, however ad-libitum energy intake did not
increase.
PMID- 28689025
TI - Venom-derived peptide inhibitors of voltage-gated potassium channels.
AB - Voltage-gated potassium channels play a key role in human physiology and
pathology. Reflecting their importance, numerous channelopathies have been
characterised that arise from mutations in these channels or from autoimmune
attack on the channels. Voltage-gated potassium channels are also the target of a
broad range of peptide toxins from venomous organisms, including sea anemones,
scorpions, spiders, snakes and cone snails; many of these peptides bind to the
channels with high potency and selectivity. In this review we describe the
various classes of peptide toxins that block these channels and illustrate the
broad range of three-dimensional structures that support channel blockade. The
therapeutic opportunities afforded by these peptides are also highlighted. This
article is part of the Special Issue entitled 'Venom-derived Peptides as
Pharmacological Tools.'
PMID- 28689026
TI - Venom peptides as pharmacological tools and therapeutics for diabetes.
AB - Diabetes mellitus is a chronic disease caused by a deficiency in production of
insulin by the beta cells of the pancreas (type 1 diabetes, T1D), or by partial
deficiency of insulin production and the ineffectiveness of the insulin produced
(type 2 diabetes, T2D). Animal venoms are a unique source of compounds targeting
ion channels and receptors in the nervous and cardiovascular systems. In recent
years, several venom peptides have also emerged as pharmacological tools and
therapeutics for T1D and T2D. Some of these peptides act directly as mimics of
endogenous metabolic hormones while others act on ion channels expressed in
pancreatic beta cells. Here, we provide an overview of the discovery of these
venom peptides, their mechanisms of action in the context of diabetes, and their
therapeutic potential for the treatment of this disease. This article is part of
the Special Issue entitled 'Venom-derived Peptides as Pharmacological Tools.'
PMID- 28689027
TI - Cross-sectoral assessment of public policies in health and the environment:
Scenario of the municipalities in the state of Sao Paulo.
AB - From the identification of the current and rising demand for integrated solutions
by government players, especially at the stage of evaluation of public policies,
this paper carried out an cross-sectoral outcome assessment of local government
cost-effectiveness in the fields of health and environment. The analysis is based
on the amount of resources allocated by each of the 645 municipalities in the
state of Sao Paulo, to each field, involving consolidated evaluation indicators
(IDSUS and IAA, respectively). This study required the prior distribution of
municipalities in clusters within homogeneous groups previously proposed in IDSUS
calculation methodology. The results suggest that the addressed areas are
intimately connected, indicating that larger (and better) environmental
investments can produce promising outcomes toward health performance. Therefore,
there is a demand for integrated public policies in the context of environmental
health. Also, there is the indication that the resource management and the proper
allocation thereof may be more relevant than the total amount spent; and that
lower cost-effectiveness values do not necessarily demonstrate high scores in the
assessed performance indicators.
PMID- 28689028
TI - Applying RE-AIM to evaluate two community-based programs designed to improve
access to eye care for those at high-risk for glaucoma.
AB - INTRODUCTION: Glaucoma is a leading cause of vision loss and blindness in the
U.S. Risk factors include African American race, older age, family history of
glaucoma, and diabetes. This paper describes the evaluation of a mobile eye
health and a telemedicine program designed to improve access to eye care among
people at high-risk for glaucoma. METHODS: The RE-AIM (reach, efficacy, adoption,
implementation, and maintenance) evaluation framework was used to harmonize
indicators. Both programs provided community-based eye health education and eye
services related to glaucoma detection and care. Each program reported data on
participants and community partners. An external evaluator conducted site visit
interviews with program staff and community partners. Quantitative and
qualitative data were integrated and analyzed using the RE-AIM dimensions.
DISCUSSION: By targeting high-risk populations and providing comprehensive eye
exams, both programs detected a large proportion of new glaucoma-related cases
(17-19%) - a much larger proportion than that found in the general population
(<2%). The educational intervention increased glaucoma knowledge; evidence that
it led people to seek eye care was inconclusive. CONCLUSIONS: Evaluation findings
from the mobile eye health program and the telemedicine program may provide
useful information for wider implementation in public health clinics and in
optometrist clinics located in retail outlets.
PMID- 28689029
TI - Course constructions: A case-base of forensic toxicology.
AB - Forensic toxicology education in China is limited by insufficient teaching
methods and resources, resulting in students with adequate theoretical principles
but lacking practice experience. Typical cases used as teaching materials vividly
represent intoxication and provide students with an opportunity to practice and
hone resolving skills. In 2013, the Department of Forensic Pathology at Zhongshan
School of Medicine began to construct top-quality courses in forensic toxicology,
with its first step, creating a base containing typical cases of intoxication.
This essay reviews the construction process of said cases-base, which is intended
to set an example of forensic toxicology education.
PMID- 28689030
TI - Risk of hospitalization for fire-related burns during extreme cold weather.
AB - BACKGROUND: Environmental factors are important predictors of fires, but no study
has examined the association between outdoor temperature and fire-related burn
injuries. We sought to investigate the relationship between extremely cold
outdoor temperatures and the risk of hospitalization for fire-related burns.
MATERIAL AND METHODS: We carried out a time-stratified case-crossover study of
2470 patients hospitalized for fire-related burn injuries during cold months
between 1989 and 2014 in Quebec, Canada. The main exposure was the minimum
outdoor temperature on the day of and the day before the burn. We computed odds
ratios (OR) and 95% confidence intervals (CI) to evaluate the relationship
between minimum temperature and fire-related burns, and assessed how associations
varied across sex and age. RESULTS: Exposure to extreme cold temperature was
associated with a significantly higher risk of hospitalization for fire-related
burns. Compared with 0 degrees C, exposure to a minimum temperature of -30
degrees C was associated with an OR of 1.51 (95% CI 1.22-1.87) for
hospitalization for fire-related burns. The associations were somewhat stronger
for women, youth, and the elderly. Compared with 0 degrees C, a minimum
temperature of -30 degrees C was associated with an OR for fire-related burn
hospitalization of 1.65 for women (95% CI 1.13-2.40), 1.60 for age < 25 years
(95% CI 1.02-2.52), and 1.73 for age >= 65 years (95% CI 1.08-2.77). DISCUSSION:
Extremely cold outdoor temperature is a risk factor for fire-related burns.
Measures to prevent fires should be implemented prior to the winter season, and
enhanced during extreme cold.
PMID- 28689031
TI - Re-defining the characteristics of environmental volunteering: Creating a
typology of community-scale green infrastructure.
AB - One way to engage people with green infrastructure (GI) is as environmental
volunteers. Previous studies explored the nature of such groups/projects in terms
of the benefits they deliver such as their impact on levels of social capital
within a pre-defined community. However, existing literature contributes little
to our understanding of the composition, characteristics and mechanisms used to
form and maintain these groups. As such, it is difficult to establish the
influencing factors determining the capacity of a group to sustain its provision
over time. This paper serves to offer a more nuanced understanding of local-scale
environmental stewardship by outlining the diversity of volunteer-led GI
activities observed at the community-scale. Evidence presented from a desk-based
examination of observable activity within The Mersey area Forest in North-West
England represents a re-conceptualisation of existing definitions of Community
Scale GI (CSGI). Using thematic criteria, the paper clusters characteristics into
key classification affecting group dynamics, composition and objectives. Initial
findings identified the following categories as being significant descriptors for
community-scale green infrastructure: status, location, timeframe, membership,
activity focus, governance, resources and recognition, and communications. Thus,
we classify four distinct types of group engaged in voluntary activity
contributing to local level GI creation and long-term management: 'Formal Group
(Active), Formal Group (Inactive), Formal Project and Informal Group. Creating a
nuanced typology of CSGI provides further opportunities to analysis the creation
and long-term management of GI at a site, neighbourhood and city-scale. In turn,
this contributes to our understanding of how multiple actors remain engaged in
the decision-making processes of GI management and maintenance.
PMID- 28689032
TI - A total diet study and probabilistic assessment risk assessment of dietary
mercury exposure among First Nations living on-reserve in Ontario, Canada.
AB - Methyl Mercury (MeHg) exposure is a global environmental health concern.
Indigenous peoples around the world are susceptible to MeHg exposure from often
higher fish consumption compared to general populations. The objective of this
study was to estimate dietary exposure to methylmercury (MeHg) among First
Nations living on-reserve in the province of Ontario, Canada. A total diet study
was constructed based on a 24-h recall from the First Nations Food, Nutrition,
and Environment Study (FNFNES), and measured contaminant concentrations from
Health Canada for market foods, and FNFNES for traditional foods. A probabilistic
assessment of annual and seasonal traditional food consumptions was conducted for
1429 adult participants. Results were compared to exposures in the general
Canadian population and reference values from Health Canada for adults and women
of childbearing age (ages 19-50). Results indicated traditional foods to be the
primary contributor to the dietary total MeHg intake (72%). The average dietary
total MeHg exposure in the First Nations population in Ontario (0.039MUg/kg/d)
was 1.6 times higher than the general Canadian population; however, the majority
(97.8%) of the population was below the reference values. Mercury concentrations
in participants' hair samples (n = 744) ranged from 0.03 to 13.54ug/g, with an
average of 0.64ug/g (geometric average of 0.27ug/g). Less than 1% of the
population had a hair mercury value above the 6ug/g level, and 1.3% of women of
child bearing age had values greater than 2ug/g. Fish species contributing to the
MeHg intake included pickerel-walleye, pike, perch and trout. Only 7.9% of the
population met the recommended fish consumption rate of two, 3.5oz servings per
week from the American Heart Association. Therefore, consumption of lower trophic
level fish can be promoted to provide the maximum nutritional benefit with
minimal risk of MeHg exposure.
PMID- 28689033
TI - Association between temperature and maternal stress during pregnancy.
AB - BACKGROUND: Maternal psychological stress during pregnancy has essentially been
conceptualized as a teratogen. However, little is known about the effect of
temperature on maternal stress during pregnancy. The aim of this study is to
investigate the relationship between temperature and maternal stress during
pregnancy. METHODS: In 2010, a total of 1931 eligible pregnant women were
enrolled across Shanghai from four prenatal-care clinics during their mid-to-late
pregnancy. Maternal life-event stress and emotional stress levels during
pregnancy were assessed by the "Life Event Scale for Pregnant Women" (LESPW) and
"Symptom Checklist-90-Revised Scale" (SCL-90-R), respectively. Exposure to
ambient temperature was evaluated based on daily regional average in different
moving average and lag days. The generalized estimating equations were used to
evaluate the relationship between daily average temperature/temperature
difference and maternal stress. RESULTS: After adjusting for relevant
confounders, an U-shaped relationship was observed between daily average
temperature and maternal Global-Severity-Index (GSI) of the SCL-90-R. Cumulative
exposures to extremely low temperatures (< P5, 1.4-10.5C, lag 0-1 days, 0-2 days
and 0-5 days) and extremely high temperatures (>= P95, 31.2-34.1C, lag 0-1 days
and 0-2 days), and acute exposures to extremely low (lag day 0, 1, 2 and 3) and
high (lag day 0, 1) temperatures, all induced higher risks of high GSI (the
highest tertile), compared to the risk induced by exposed to an optimal
temperature range (20-25C) (P< 0.05). Increased temperature difference was
associated with high maternal GSI (P< 0.05). However, non-significant
associations were observed between daily average temperatures/temperature
differences and maternal log-transferred LESPW scores. CONCLUSIONS: Cumulative
and acute exposures to extremely low/high temperatures may both induce emotional
stress during pregnancy.
PMID- 28689034
TI - Solid fuel use is associated with anemia in children.
AB - Over 3 billion people use solid fuels as a means of energy and heating source,
and ~ 50% of households burn them in inefficient, poorly ventilated stoves. In
2010, ~ 43% of the 640 million preschool children in 220 countries suffered from
a certain degree of anemia, with iron deficiency as the main cause in developed
countries whereas its causes remained multifactorial in the undeveloped group. In
this study, we explore the relations of country-wide variables that might affect
the people's health status (from socioeconomic status to more specific variables
such as water access). We found independent relationship between solid fuel use
and anemia in children under five years old (p < 0.0001), taking into account the
prevalence of anemia in pregnant woman and the access to improved water sources.
Countries in which the population uses solid fuel the most have over three times
higher anemia rates in children than countries with the lowest prevalence of
solid fuels use. There is still a complex relationship between solid fuels use
and anemia, as reflected in its worldwide significance (p < 0.05) controlled for
measles immunization, tobacco consumption, anemia in pregnant mothers, girl's
primary education, life expectancy and improved water access but not (p > 0.05)
when weighing for sanitation access or income per capita.
PMID- 28689035
TI - Causative impact of air pollution on evapotranspiration in the North China Plain.
AB - Atmospheric dispersion conditions strongly impact air pollution under identical
surface emissions. The degree of air pollution in the Jing-Jin-Ji region is so
severe that it may impose feedback on local climate. Reference evapotranspiration
(ET0) plays a significant role in the estimation of crop water requirements, as
well as in studies on climate variation and change. Since the traditional
correlation analysis cannot capture the causality, we apply the convergent cross
mapping method (CCM) in this study to observationally investigate whether the air
pollution impacts ET0. The results indicate that southwest regions of Jing-Jin-Ji
always suffer higher PM2.5 concentration than north regions through the whole
year, and correlation analysis suggests that PM2.5 concentration has a
significant negative effect on ET0 in most cities. The causality detection with
CCM quantitatively demonstrates the significantly causative influence of PM2.5
concentration on ET0, higher PM2.5 concentration decreasing ET0. However, CCM
analysis suggests that PM2.5 concentration has a relatively weak causal influence
on ET0 while the correlation analysis gives the near zero correlation coefficient
in Zhangjiakou city, indicating that the causative influence of PM2.5
concentration on ET0 is better revealed with CCM method than the correlation
analysis. Considering that ET0 is strongly associated with crop water
requirement, the amount of water for agricultural irrigation could be reduced at
high PM2.5 concentrations. These findings can be utilized to improve the
efficiency of water resources utilization, and reduce the exploiting amount of
groundwater in the Jing-Jin-Ji region, although PM2.5 is detrimental to human
health.
PMID- 28689036
TI - Enhanced vasculotoxic metal excretion in post-myocardial infarction patients
following a single edetate disodium-based infusion.
AB - : Toxic metals have been associated with cardiovascular mortality and morbidity.
We have hypothesized that enhanced excretion of vasculotoxic metals might explain
the positive results of the Trial to Assess Chelation Therapy (TACT). The purpose
of this study was to determine whether a single infusion of the edetate disodium-
based infusion used in TACT led to enhanced excretion of toxic metals known to be
associated with cardiovascular events. METHODS: Twenty six patients (post-MI, age
> 50 years, serum creatinine <= 2.0mg/dL) were enrolled in this open-label study.
Urinary levels of 20 toxic metals normalized to urinary creatinine concentrations
were measured at baseline in overnight urine collections, for 6h following a
placebo infusion of 500mL normal saline and 1.2% dextrose, and for 6h following a
3g edetate disodium-based infusion. Self-reported metal exposure, smoking status,
food frequency, occupational history, drinking water source, housing and hobbies
were collected at baseline by a metal exposure questionnaire. RESULTS: The mean
age was 65 years (range 51-81 years). All patients were male. 50% had diabetes
mellitus and 58% were former smokers. Mean (SD) serum creatinine was 0.95 (0.31)
mg/dL. Toxic metals were detected in the baseline urine of >80% of patients.
After placebo infusion there were no significant changes in total urinary metal
levels. After edetate infusion, total urinary metal level increased by 71%
compared to baseline (1500 vs. 2580ug/g creatinine; P<0.0001). The effect of
edetate was particularly large for lead (3835% increase) and cadmium (633%
increase). CONCLUSIONS: Edetate disodium-based infusions markedly enhanced the
urinary excretion of lead and cadmium, toxic metals with established
epidemiologic evidence and mechanisms linking them to coronary and vascular
events.
PMID- 28689037
TI - Association of donor and recipient SUMO4 rs237025 genetic variant with new-onset
diabetes mellitus after liver transplantation in a Chinese population.
AB - BACKGROUNDS & AIMS: New-onset diabetes mellitus (NODM) is a common complication
after liver transplantation (LT). The small ubiquitin-like modifier 4 (SUMO4)
rs237025 polymorphism has been reported to be associated with type 2 diabetes
mellitus (T2DM). In this study, we aimed to evaluate the association of donor and
recipient SUMO4 rs237025 polymorphisms with NODM and the long-term consequences
of NODM after LT. METHODS: A total of 126 liver transplant patients were enrolled
in the study. One single nucleotide polymorphism, SUMO4 rs237025, was genotyped
in both donors and recipients. RESULTS: Both donor and recipient SUMO4 rs237025
polymorphisms were found to be significantly associated with NODM after LT. In
multivariate analysis, recipient age>50 years, tacrolimus trough
concentrations>10ng/mL at 1month after LT, donor and recipient rs237025 genetic
variant, and the combined donor and recipient rs237025 genetic variant were
independent predictive factors of NODM. Area under the receiver operating
characteristic curve (AUROC) analysis indicated the higher predictive ability of
the model containing combined donor and recipient rs237025 polymorphisms than the
clinical model (p=0.046). Furthermore, Kaplan-Meier survival analysis
demonstrated that NODM was related to significantly poorer patient survival in
comparison with non-NODM patients (p=0.041). CONCLUSIONS: Both donor and
recipient SUMO4 rs237025 polymorphisms contribute to the development of NODM
after LT and NODM is a frequent complication that negatively affects patient
survival.
PMID- 28689038
TI - A phylogenetic view of the Out of Asia/Eurasia and Out of Africa hypotheses in
the light of recent molecular and palaeontological finds.
AB - The substantiality of the Out of Africa hypothesis was addressed in the light of
recent genomic analysis of extant humans (Homo sapiens sapiens, Hss) and progress
in Neanderthal palaeontology. The examination lent no support to the commonly
assumed Out of Africa scenario but favoured instead a Eurasian divergence between
Neanderthals and Hss (the Askur/Embla hypothesis) and an Out of Asia/Eurasia
hypothesis according to which all other parts of the world were colonized by Hss
migrations from Asia. The examination suggested furthermore that the ancestors of
extant KhoeSan and Mbuti composed the first Hss dispersal(s) into Africa and that
the ancestors of Yoruba made up a later wave into the same continent. The
conclusions constitute a change in paradigm for the study of human evolution.
PMID- 28689039
TI - Connexin43, but not connexin30, contributes to adult neurogenesis in the dentate
gyrus.
AB - The subgranular zone of the dentate gyrus represents a niche in which radial glia
(RG)-like cells generate new neurons throughout postnatal life in the mammalian
brain. Previous data showed that RG-like cells are coupled through gap junction
channels, primarily formed by connexin43 (Cx43) and Cx30, and that the expression
of these proteins is required for adult neurogenesis in the hippocampus. However,
their individual function and underlying mechanisms remain unclear. Here we
demonstrate that Cx43, but not Cx30, is crucial for adult neurogenesis. To assess
whether Cx43-dependent intercellular coupling between RG-like cells or rather
channel-independent interactions of the protein regulate neurogenesis, mice
bearing a Cx43 point mutation (Cx43G138R) in RG-like cells and protoplasmic
astrocytes cells were employed, which was expected to cause channel closure
without affecting the trafficking of the protein to the membrane. We confirmed
the disruption of coupling between RG-like cells and astrocytes in the
hippocampus of Cx43G138R mice. Proliferative activity and neurogenesis in the DG
were significantly decreased in the mutant mouse line, indicating that functional
Cx43 channels are essential for proper adult neurogenesis. The fate of
proliferating cells in the DG was not affected by Cx43 mutation as revealed by 5
bromo-2-deoxyuridine (BrdU) incorporation assays. Together, these findings
suggest that adult neurogenesis in the hippocampus does not require Cx30 but
channel-dependent functions of Cx43.
PMID- 28689040
TI - Unsupervised learning techniques reveal heterogeneity in memory CD8+ T cell
differentiation following acute, chronic and latent viral infections.
AB - CD8+ T lymphocytes are critical for the control of gammaherpesvirus latency. To
determine how memory CD8+ T cells generated during latency differ from those
primed during acute or chronic viral infection, we adoptively transferred naive
P14 CD8+ T cells into uninfected recipients, and examined surface proteins,
cytokines and transcription factors following infection with the Armstrong
(acute) or Clone 13 (chronic) strains of lymphocytic choriomeningitis virus
(LCMV), or murine gammaherpesvirus 68 (MHV68) expressing the LCMV epitope DbGP33
41. By performing k-means clustering and generating self organizing maps (SOM),
we observed increased short-lived effector-like, CD27lo CD62Llo and Bcl-6lo CD8+
T cells following latent infection. In addition, we found that memory CD8+ T
cells from latent primed mice underwent less expansion following adoptive
transfer and antigen rechallenge. Data from cluster models were combined and
visualized by principal component analysis (PCA) demonstrating memory CD8+ T
cells from latent infection occupy an intermediate differentiation space.
PMID- 28689041
TI - Exposure and non-fear emotions: A randomized controlled study of exposure-based
and rescripting-based imagery in PTSD treatment.
AB - Interventions involving rescripting-based imagery have been proposed as a better
approach than exposure-based imagery when posttraumatic stress disorder (PTSD) is
associated with emotions other than fear. Prior research led to the study's
hypotheses that (a) higher pretreatment non-fear emotions would predict
relatively better response to rescripting as compared to exposure, (b)
rescripting would be associated with greater reduction in non-fear emotions, and
(c) pretreatment non-fear emotions would predict poor response to exposure. A
clinically representative sample of 65 patients presenting a wide range of
traumas was recruited from patients seeking and being offered PTSD treatment in
an inpatient setting. Subjects were randomly assigned to 10 weeks of treatment
involving either rescripting-based imagery (Imagery Rescripting; IR) or exposure
based imagery (Prolonged Exposure; PE). Patients were assessed on outcome and
emotion measures at pretreatment, posttreatment and 12 months follow-up.
Comparison to control benchmarks indicated that both treatments were effective,
but no outcome differences between them appeared. None of the initial hypotheses
were supported. The results from this study challenge previous observations and
hypotheses about exposure mainly being effective for fear-based PTSD and
strengthen the notion that exposure-based treatment is a generally effective
treatment for all types of PTSD.
PMID- 28689042
TI - Historical demography and longevity genetics: Back to the future.
AB - Research into the genetic component of human longevity can provide important
insights in mechanisms that may protect against age-related diseases and multi
morbidity. Thus far only a limited number of robust longevity loci have been
detected in either candidate or genome wide association studies. One of the
issues in these genetic studies is the definition of the trait being either
lifespan, including any age at death or longevity, i.e. survival above a diverse
series of thresholds. Likewise heritability and segregation research have
conflated lifespan with longevity. The heritability of lifespan estimated across
most studies has been rather low. Environmental factors have not been
sufficiently investigated and the total amount of genetic variance contributing
to longevity has not been estimated in sufficiently well-defined and powered
studies. Up to now, genetic longevity studies lack the required insights into the
nature and size of the genetic component and the optimal strategies for meta
analysis and subject selection for Next Generation Sequencing efforts. Historical
demographic data containing deep genealogical information may help in estimating
the best definition and heritability for longevity, its transmission patterns in
multi-generational datasets and may allow relevant additive and modifying
environmental factors such as socio-economic status, geographical background,
exposure to environmental effects, birth order, and number of children to be
included. In this light historical demographic data may be very useful for
identifying lineages in human populations that are worth investigating further by
geneticists.
PMID- 28689044
TI - Voyaging into the third dimension: A perspective on virtual methods and their
application to studies of juvenile sex estimation and the ontogeny of sexual
dimorphism.
AB - In contrast to the well-established and highly accurate morphological methods
available for sexing adult skeletons, juvenile sex estimation is widely
recognised as a difficult task that faces a series of challenges. The acquisition
of 3D data, and construction of 3D models from volume or surface scans, has
become increasingly common in forensic sciences, and these data offer
considerable opportunity for the development and refinement of methods in sex
estimation. The suitability and potential of virtual methods for juvenile sex
estimation are evaluated with the aims of identifying (1) the benefits and
challenges associated with virtual data and quantitative analysis of 3D models,
and (2) pathways that may lead to practical improvements for sexing juveniles.
The issues associated with sex estimation in juveniles are discussed and
approached in the context of a framework that unifies classification results for
a given trait, which provide information on its capacity to discriminate between
the sexes, with the underlying patterns of dimorphism over ontogeny. Virtual
collections of 3D models are suggested as integral to this framework because they
enable the magnitude and mode of sexual dimorphism to be comprehensively
quantified for a chosen trait or set of traits. Those data can be used to inform
decisions about how to apply a method for sex estimation to maximize its success.
Virtual collections, through extending the scope of analyses and impacting the
way in which questions on sexual dimorphism in juveniles may be answered, are
undoubtedly set to play a central role in future research.
PMID- 28689043
TI - Pooled Systemic Efficacy and Safety Data from the Pivotal Phase II Studies
(NP28673 and NP28761) of Alectinib in ALK-positive Non-Small Cell Lung Cancer.
AB - INTRODUCTION: Alectinib demonstrated clinical efficacy and an acceptable safety
profile in two phase II studies (NP28761 and NP28673). Here we report the pooled
efficacy and safety data after 15 and 18 months more follow-up than in the
respective primary analyses. METHODS: Enrolled patients had ALK receptor tyrosine
kinase gene (ALK)-positive NSCLC and had progressed while taking, or could not
tolerate, crizotinib. Patients received oral alectinib, 600 mg twice daily. The
primary end point in both studies was objective response rate assessed by an
independent review committee (IRC) using the Response Evaluation Criteria in
Solid Tumors, version 1.1. Secondary end points included disease control rate,
duration of response, progression-free survival, overall survival, and safety.
RESULTS: The pooled data set included 225 patients (n = 138 in NP28673 and n = 87
in NP28761). The response-evaluable population included 189 patients (84% [n =
122 in NP28673 and n = 67 in NP28761]). In the response-evaluable population,
objective response rate as assessed by the IRC was 51.3% (95% confidence interval
[CI]: 44.0-58.6 [all PRs]), the disease control rate was 78.8% (95% CI: 72.3
84.4), and the median duration of response was 14.9 months (95% CI: 11.1-20.4)
after 58% of events. Median progression-free survival as assessed by the IRC was
8.3 months (95% CI: 7.0-11.3) and median overall survival was 26.0 months (95%
CI: 21.4-not estimable). Grade 3 or higher adverse events (AEs) occurred in 40%
of patients, 6% of patients had treatment withdrawn on account of AEs, and 33%
had AEs leading to dose interruptions/modification. CONCLUSIONS: This pooled data
analysis confirmed the robust systemic efficacy of alectinib in ALK-positive
NSCLC with a durable response rate. Alectinib also had an acceptable safety
profile with a longer duration of follow-up.
PMID- 28689045
TI - Estimation of changes in breech face and firing pin marks over consecutive
discharges and its impact on an IBIS(r) HeritageTM System.
AB - When a firearm is discharged, the individual marks of the breech face and firing
pin are imprinted onto the primer of the cartridge case. These individual marks
are reproducible between shots; however, over a large number of consecutive
shots, it has been observed that minute changes in these individual marks may
occur. Changes in individual marks may affect an examiner in their ability to
identify or eliminate and may change the magnitude of a likelihood ratio,
depending on the system used by the laboratory, but the effect that these changes
have on the Integrated Ballistic Identification System (IBIS(r)) is largely
unknown. If such changes negatively affect the performance of the IBIS(r) then
consequences may result with respect to the correct matching candidate not be
returned in the top results further compared by an examiner. Two hundred
consecutive test fires performed in a clean environment (indoor shooting range)
were collected in sequence from 24 new Ruger(r) SR9 9mm pistols and entered into
an IBIS(r) HeritageTM System. The full known match data were extracted for each
firearm, and delta sets were created that had a specific number of cartridge
cases between the two cartridge cases being compared. Receiver operating
characteristic (ROC) area under the curve (AUC) values for these delta sets were
compared to the full known match sets to determine if any significant changes in
performance resulted. Although there were instances of significant differences,
these only occurred in less than 25% of comparisons, and overall no decreasing
trends in performance were observed.
PMID- 28689046
TI - Post-admission outcomes of participants in the PARAMEDIC trial: A cluster
randomised trial of mechanical or manual chest compressions.
AB - BACKGROUND: The PARAMEDIC cluster randomised trial evaluated the LUCAS mechanical
chest compression device, and did not find evidence that use of mechanical chest
compression led to an improvement in survival at 30 days. This paper reports
patient outcomes from admission to hospital to 12 months after randomisation.
METHODS: Information about hospital length of stay and intensive care management
was obtained through linkage with Hospital Episode Statistics and the Intensive
Care National Audit and Research Centre. Patients surviving to hospital discharge
were approached to complete questionnaires (SF-12v2, EQ-5D, MMSE, HADS and PTSD
CL) at 90days and 12 months. The study is registered with Current Controlled
Trials, number ISRCTN08233942. RESULTS: 377 patients in the LUCAS arm and 658
patients in the manual chest compression were admitted to hospital. Hospital and
intensive care length of stay were similar. Long term follow-up assessments were
limited by poor response rates (53.7% at 3 months and 55.6% at 12 months). Follow
up rates were lower in those with worse neurological function. Among respondents,
long term health related quality of life outcomes and emotional well-being was
similar between groups. Cognitive function, measured by MMSE, was marginally
lower in the LUCAS arm mean 26.9 (SD 3.7) compared to control mean 28.0 (SD 2.3),
adjusted mean difference -1.5 (95% CI -2.6 to -0.4). CONCLUSION: There were no
clinically important differences identified in outcomes at long term follow-up
between those allocated to the mechanical chest compression compared to those
receiving manual chest compression.
PMID- 28689047
TI - Major regional differences in Automated External Defibrillator placement and
Basic Life Support training in France: Further needs for coordinated
implementation.
AB - BACKGROUND: Public Access Defibrillation (PAD) programs have emerged since mid
1990s with the aim of improving survival from Out-of-Hospital Cardiac Arrest
(OHCA). The extent to which their implementation in the community differs among
different areas has not been evaluated. METHODS: We carried out a 5-year
prospective national evaluation of PAD programs in 51 French districts (29.3
million inhabitants), through the cumulative density of Automated External
Defibrillator (AEDs) and the proportion of persons educated in Basic Life Support
(BLS). RESULTS: Major regional discrepancies were observed with AED density from
5 to 3399 per 100,000 inhabitants per 1000km2, and BLS-educated inhabitants
varying from 6955 to 36,636 per 100,000 inhabitants. Only 18 districts (35.3%)
achieved both AED density and educational rate above median (>13,988 and >22,
respectively). Extrapolating the data from the French national registry on sports
OHCA, mean survival rate was two-folds higher with AED density above the median
(7.9% vs. 17.8%, P<0.001) and four-fold higher with BLS-education above the
median (5.0% vs. 20.9%, P<0.001). In the group with both AED density and BLS
education level above the median, the survival rate reached up to 22.5%. Only the
rate of population BLS education remained independently associated with survival
(OR 1.64, 95% Confidence Interval 1.17-2.31; P=0.0045). CONCLUSIONS: Major
heterogeneities in PAD programs exist, with significant room for better
coordination in implementation. Population education in BLS provides an important
benefit, regardless of the density of AEDs deployed, which should be taken into
account in planning public health policies for improving OHCA survival.
PMID- 28689048
TI - The impact of hypothermia on serum potassium concentration: A systematic review.
AB - BACKGROUND: Blood potassium is the main prognostic biomarker used for triage in
hypothermic cardiac arrest. The aim of this review was to assess the impact of
hypothermia on blood potassium levels and compare the underlying
pathophysiological theories. METHODS: The Medline electronic database was
searched via PubMed for articles published from January 1970 to December 2016.
The search strategy included studies related to hypothermia and potassium levels.
The relevant literature on clinical studies and experimental studies was reviewed
by the authors. RESULTS: Among the 50 studies included in the review, 39 (78%)
reported a decrease in blood potassium levels upon hypothermia onset. Hypothermic
hypokalaemia is linked to an intracellular shift rather than an actual net loss.
The intracellular shift is caused by a variety of factors such as enhanced
functioning of Na+K+ATPase, beta-adrenergic stimulation, pH and membrane
stabilisation in deep hypothermia. In contrast, hypothermia can act as an
aggravating factor in severe trauma with hyperkalaemia being an indicator of an
irreversible state of cell death. An increase in the blood potassium level during
hypothermia may result from a lack of enzyme functioning at cold temperatures and
blocked active transport. CONCLUSION: Hypothermia causes an initial decrease of
potassium levels; however, the final stage of hypothermic cardiac arrest can
induce hyperkalaemia due to cell lysis and final depolarisation. Better
understanding the physiopathology of potassium levels during accidental
hypothermia could be critically important to better select patients who could
benefit from aggressive resuscitation therapy such as extracorporeal
cardiopulmonary resuscitation.
PMID- 28689049
TI - The spatiotemporal relationships between chondroitin sulfate proteoglycans and
terminations of calcitonin gene related peptide and parvalbumin immunoreactive
afferents in the spinal cord of mouse embryos.
AB - Chondroitin sulfate (CS) proteoglycans (PGs) are a family of complex molecules in
the extracellular matrix and cell surface that regulate axon growth and guidance
during development of the central nervous system. In this study, the expression
of CSPGs was investigated in the mouse spinal cord at late embryonic and neonatal
stages using CS-56 antibody. CS immunoreactivity was observed abundantly in
ventral regions of spinal cord of embryonic day (E) 15 embryos. At E16 to E18, CS
expression spread dorsally, but never reached the superficial layers of the
dorsal horn. This pattern was maintained until postnatal day 4, the latest stage
examined. Antibodies against calcitonin gene related peptide (CGRP) and
parvalbumin (PV) were employed to label primary afferents from nociceptors and
proprioceptors, respectively. CGRP-immunoreactive fibers terminated in the
superficial regions of the dorsal horn where CSPGs were weakly expressed, whereas
PV-immunoreactive fibers were found in CSPG-rich regions in the ventral horn.
Therefore, we conclude that CS expression is spatiotemporally regulated in the
spinal cord, which correlates to the termination of sensory afferents. This
pattern suggests a role of CSPGs on patterning afferents in the spinal cord,
probably through a differential response of axons to these growth inhibitory
molecules.
PMID- 28689050
TI - Self-reported traumatic brain injury and in vivo measure of AD-vulnerable
cortical thickness and AD-related biomarkers in the ADNI cohort.
AB - In this study, we aimed to investigate whether self-reported mild traumatic brain
injury (mTBI) was associated with decreased AD-vulnerable cortical thickness, and
to assess the relationship between AD-vulnerable cortical thickness and AD
related biomarker in the Alzheimer's Disease Neuroimaging Initiative subjects. We
identified 45 self-reported mTBI subjects, who had structural MRI, 18F-AV45 PET,
and cerebrospinal fluid (CSF) data. Of them, eight subjects were normal; ten were
preclinical AD; seventeen were MCI due to AD; ten were AD. Additional
demographics-controlled 45 subjects were included. Cortical thickness of eight AD
vulnerable regions, mean AD-vulnerable cortical thickness, 18F-AV45 PET mean
amyloid SUVR, CSF Abeta42, CSF total tau (T-tau), and CSF phosphorylated tau (P
tau) were compared between mTBI and non-TBI groups. Correlational analysis was
done to investigate the relationship between mean AD-vulnerable cortical
thickness and mean amyloid SUVR, CSF Abeta42, CSF T-Tau, CSF P-Tau. Our study
revealed that preclinical AD subjects with self-reported mTBI had smaller
cortical thickness in mean and three AD-vulnerable cortical regions than non-TBI
subjects (P<0.05). The mean AD-vulnerable cortical thickness was correlated with
CSF T-tau (r=-0.81, P=0.001). There was no statistical difference in the
comparison of normal, MCI due to AD, and AD groups. Our study indicated that
among individuals with preclinical AD, but not normal, MCI due to AD and AD
subjects, self-reported mTBI was associated with more decreased AD-vulnerable
cortical thickness which was related to CSF tau pathology, suggesting the
possible early involvement of tau pathology in the decreased AD-vulnerable
cortical thickness of self-reported TBI subjects.
PMID- 28689051
TI - Projection targets of medial frontal D1DR-expressing neurons.
AB - Prefrontal neurons expressing D1-type dopamine receptors (D1DRs) have been
implicated in a variety of cognitive processes including working memory and
timing. Although D1DRs are most strongly expressed on layer V/VI projection
neurons, it is unknown which brain areas are specifically targeted by these
projections. Here we selectively marked D1DR neurons using cre-loxP techniques
with AAV carrying mCherry fluorescent protein, and traced projection targets of
D1DR+ neurons in the mouse medial frontal cortex (MFC). We found relatively
strong MFC D1DR+ projections to cortical areas as well as projections to basal
ganglia and thalamic nuclei. We found relatively weaker MFC D1DR+ projections to
the brainstem, hypothalamus, and other subcortical nuclei. These data intimate
that MFC D1DR+ projections are well-positioned to powerfully influence cortical
processing and have subcortical specificity. Thus MFC D1DR+ projection neurons
may play a key role in tuning cortical networks during goal-directed behavior.
PMID- 28689052
TI - Directing iron transport in dicots: regulation of iron acquisition and
translocation.
AB - Iron is essential for plant growth and development, but excess iron is cytotoxic.
While iron is abundant in soil, it is often a limiting nutrient for plant growth.
Consequentially, plants have evolved mechanisms to tightly regulate iron uptake,
trafficking and storage. Recent work has contributed to a more comprehensive
picture of iron uptake, further elucidating molecular and physiological processes
that aid in solubilization of iron and modulation of the root system architecture
in response to iron availability. Recent progress in understanding the regulators
of the iron deficiency response and iron translocation from root to shoots, and
especially to seeds are noteworthy. The molecular bases of iron sensing and
signaling are gradually emerging, as well.
PMID- 28689053
TI - Schema benefit vs. proactive interference: Contradicting behavioral outcomes and
coexisting neural patterns.
AB - Prior knowledge can either assist or hinder the ability to learn new information.
These contradicting behavioral outcomes, referred to as schema benefit and
proactive interference respectively, have been studied separately. Here we
examined whether the known neural correlates of each process coexist, and how
they are influenced by attentional loading and aging. To this end we used an fMRI
task that affected both processes simultaneously by presenting pairs of related
short movies in succession. The first movie of each pair provided context for the
second movie, which could evoke schema benefit and/or proactive interference.
Inclusion of an easy or hard secondary task performed during encoding of the
movies, as well as testing both younger (22-35y) and older (65-79y) adults,
allowed examining the effect of attentional load and older age on the neural
patterns associated with context. Analyses focused on three predefined regions
and examined how their inter-subject correlation (inter-SC) and functional
connectivity (FC) with the hippocampi changed between the first and second movie.
The results in the medial prefrontal cortex (mPFC) and posterior cingulate cortex
(PCC) matched and expanded previous findings: higher inter-SC and lower FC were
observed during the second compared to the first movie; yet the differentiation
between the first and second movies in these regions was attenuated under high
attentional load, pointing to dependency on attentional resources. Instead, at
high load there was a significant context effect in the FC of the left
ventrolateral prefrontal cortex (vlPFC), and greater FC in the second movie was
related to greater proactive interference. Further, older adults showed context
effect in the PCC and vlPFC. Intriguingly, older adults with inter-SC mPFC
patterns similar to younger adults exhibited schema benefit in our task, while
those with inter-SC PCC patterns similar to younger adults showed proactive
interference in an independent task. The brain-behavior relationships corroborate
the functional significance of these regions and indicate that the mPFC mainly
contributes to schema benefit, while the left vlPFC and PCC contribute to
proactive interference. Importantly, our findings show that the functions of the
regions are retained throughout the lifespan and may predict the predominant
behavioral outcome.
PMID- 28689054
TI - Implementing QM in docking calculations: is it a waste of computational time?
AB - The greatest challenge in molecular docking (MD) is the deficiency of scoring
functions (SFs), which limits their reliability. SFs are too simplified to
represent the true features of the complex free energy of protein-ligand
interactions. Investigations of docking functions have traded accuracy for speed
through the use of approximations and simplifications. Consequently, there has
been an increase in the popularity of quantum-mechanical (QM)-based methods as
reference points for the development of fast, reliable, valuable, yet
inexpensive, tools. As we discuss here, one significant QM-based parameter used
to predict docking is the accuracy of atomic partial charges, which is strongly
related to the accuracy of the SF prediction.
PMID- 28689055
TI - Completeness of breast cancer operative reports in a community care setting.
AB - OBJECTIVES: The narrative operative report represents the traditional means by
which breast cancer surgery has been documented. Previous work has established
that omissions occur in narrative operative reports produced in an academic
setting. The goal of this study was to determine the completeness of breast
cancer narrative operative reports produced in a community care setting and to
explore the effect of a surgeon's case volume and years in practice on the
completeness of these reports. MATERIALS AND METHODS: A standardized
retrospective review of operative reports produced over a consecutive 2 year
period was performed using a set of procedure-specific elements identified
through a review of the relevant literature and work done locally. RESULTS: 772
operative reports were reviewed. 45% of all elements were completely documented.
A small positive trend was observed between case volume and completeness while a
small negative trend was observed between years in practice and completeness.
CONCLUSION: The dictated narrative report inadequately documents breast cancer
surgery irrespective of the recording surgeon's volume or experience. An
intervention, such as the implementation of synoptic reporting, should be
considered in an effort to maximize the utility of the breast cancer operative
report.
PMID- 28689056
TI - Patient navigation for lung cancer screening in an urban safety-net system:
Protocol for a pragmatic randomized clinical trial.
AB - The National Lung Screening Trial demonstrated improved lung cancer mortality
with annual low-dose computed tomography (CT) screening, leading to lung cancer
screening endorsement by the United States Preventive Services Task Force and
coverage by the Centers for Medicare and Medicaid. Adherence to annual CT screens
in that trial was 95%, which may not be representative of real-world,
particularly medically underserved populations. This pragmatic trial will
determine the effect of patient-focused, telephone-based patient navigation on
adherence to CT-based lung cancer screening in an urban safety-net population.
340 adults who meet standard eligibility for lung cancer screening (age 55
77years, smoking history>=30 pack-years, quit within 15years if former smoker)
are referred through an electronic medical record-based order by physicians in
community- and hospital-based primary care settings within the Parkland Health
and Hospital System in Dallas County, Texas. Eligible patients are randomized to
usual care or patient navigation, which addresses adherence, patient-reported
barriers, smoking cessation, and psycho-social concerns related to screening
completion. Patients complete surveys and semi-structured interviews at baseline,
6-month, and 18-month follow-ups to assess attitudes toward screening. The
primary endpoint of this pragmatic trial is adherence to three sequential,
prospectively defined steps in the screening protocol. Secondary endpoints
include self-reported tobacco use and other patient-reported outcomes. Results
will provide real-world insight into the impact of patient navigation on
adherence to CT-based lung cancer screening in a medically underserved
population. This study was registered with the NIH ClinicalTrials.gov database
(NCT02758054) on April 26, 2016.
PMID- 28689057
TI - Microbial activity and the dynamics of ecosystem processes in forest soils.
AB - Microbial activity in forest soils is driven by the dynamics of ecosystem
processes, largely dependent on trees as the major primary producers. Diurnal
variation of root activity, seasonality of photosynthate production or
recalcitrance of decomposing plant biomass all affect microbial abundance,
composition of their communities and activity. Due to low N content, fungi appear
to be the major decomposers of complex plant biomass: litter and deadwood and to
largely shape associated bacterial communities and their activity. On the other
hand, bacteria are important in decomposition of fungal mycelia and N-cycle
processes including N-fixation. Microbial activity is also affected in the short
term by climatic events and in the long-term by ecosystem development after
disturbances.
PMID- 28689058
TI - Protective effect of crocin on BPA-induced liver toxicity in rats through
inhibition of oxidative stress and downregulation of MAPK and MAPKAP signaling
pathway and miRNA-122 expression.
AB - Bisphenol A (BPA) is an artificial environmental endocrine disrupting chemical
and commonly used as a monomer of polycarbonate plastics and epoxy resins. The
aim of the present study is to investigate the hepatoprotective effects of
crocin, a constituent of saffron, against BPA-induced liver toxicity. We showed
that treatment of male Wistar rats with 0.5 mg/kg BPA for 30 days increased the
level of 8-isoprostane, decreased the level of reduced glutathione, elevated
serum levels of aspartate aminotransferase, lactate dehydrogenase, triglyceride,
and glucose, and induced periportal inflammation. Western blot results revealed
that BPA increased the phosphorylation of c-Jun N-terminal kinase (JNK),
extracellular signal-regulated kinase (ERK1/2), and mitogen-activated protein
kinase-activated protein kinase (MAPKAPK), but not p38. BPA also reduced the Akt
signaling activation and upregulated microRNA (miR-122) expression. Moreover, we
showed here that crocin 20 mg/kg administration ameliorated liver damage and
improved elevated levels of TG and liver enzymes of BPA-treated rats possibly
though antioxidant activity, downregulation of miR-122 transcript level and
lowering the phosphorylation of JNK, ERK1/2, and MAPKAPK and subsequently their
activities. Overall, the findings suggest that crocin possesses hepatoprotective
effects against BPA-induced liver toxicity by enhancing the antioxidative defense
system and regulation of important signaling pathway activities and miR-122
expression.
PMID- 28689059
TI - Epigenetic modulations in nanoparticle-mediated toxicity.
AB - The increasing application of nanoparticles in healthcare and consumer products
has made them ever present in our lives. However, constant exposure to these
nanoparticles has raised concerns regarding their adverse side effects on human
health, signifying the great importance of nanotoxicity studies. Indeed,
extensive in vitro and in vivo studies in this field have provided valuable
insights into the potential cytotoxicity and genotoxicity induced by
nanoparticles. Interestingly, there is a growing body of evidence that
nanoparticles can also induce epigenetic changes. In particular, several studies
have explored the alterations in DNA methylation patterns, histone modifications
and miRNA expressions upon exposure to the different types of nanoparticles. In
this review, we focused on the identified epigenetic modulations in nanoparticle
mediated toxicity, and proposed future challenges that remain to be addressed.
PMID- 28689060
TI - Proteomic evaluation of mouse adipose tissue and liver following hydroxytyrosol
supplementation.
AB - BACKGROUND AND AIMS: Hydroxytyrosol (HT) is the primary phenolic compound of
olives, virgin olive oil, and their byproducts. Proteomic analysis of
metabolically active tissues helps elucidating novel mechanisms of action and
potential targets in cardiometabolic disease. Thus, we aimed at determining the
impact of long-term HT supplementation on the proteome of adipose and liver
tissue, in mice. METHODS: C57BL/6J mice received either a control diet or a diet
supplemented with nutritionally relevant doses of HT for eight weeks. RESULTS: HT
supplementation differentially affects the adipose and liver tissues proteome, as
evaluated by super-SILAC. Some oxidative stress-related proteins were modulated
in both tissues, such as the multifunctional protein peroxiredoxin 1, which was
consistently repressed by HT supplementation. In some cases tissue-dependent
modulation was observed, as in the case of FASN. CONCLUSIONS: This study provides
interesting information on the connection between changes seen at tissue proteome
level and the metabolic effects of HT. The use of this pertinent proteomics
quantification approach may prove quite useful for uncovering novel potential
pharmaco-nutritional targets of HT supplementation.
PMID- 28689061
TI - beta-Cryptoxanthin ameliorates metabolic risk factors by regulating NF-kappaB and
Nrf2 pathways in insulin resistance induced by high-fat diet in rodents.
AB - The aim of this experiment was to determine the effects of beta-cryptoxanthin
(BCX) on the cardiometabolic health risk factors and NF-kappaB and Nrf2 pathway
in insulin resistance induced by high-fat diet (HFD) in rodents. Twenty-eight
Sprague-Dawley rats were allocated into four groups: (1) Control, rats fed a
standard diet for 12 weeks; (2) BCX, rats fed a standard diet and supplemented
with BCX (2.5 mg/kg BW) for 12 weeks; (3) HFD, rats fed a HFD for 12 weeks, (4)
HFD + BCX, rats fed a HFD and supplemented with BCX for 12 weeks. BCX reduced
cardio-metabolic health markers and decreased inflammatory markers (P < 0.001).
Rats fed a HFD had the lower total antioxidant capacity and antioxidant enzymes
activities and higher MDA concentration than control rats (P < 0.001 for all).
Comparing with the HFD group, BCX in combination with HFD inhibited liver NF
kappaB and TNF-alpha expression by 22% and 14% and enhanced liver Nrf2, HO-1,
PPAR-alpha, and p-IRS-1 by 1.43, 1.41, 3.53, and 1.33 fold, respectively (P <
0.001). Furthermore, in adipose tissue, BCX up-regulated Nrf2, HO-1, PPAR-alpha,
and p-IRS-1 expression, whereas, down-regulated NF-kappaB and TNF-alpha
expression. In conclusion, BCX decreased visceral fat and cardiometabolic health
risk factors through modulating expressions of nuclear transcription factors.
PMID- 28689062
TI - Sweeteners as food additives in the XXI century: A review of what is known, and
what is to come.
AB - Sweet has always been a very important basic taste for mankind, although
sweetness is always related to either weight gain or teeth decay. Sweeteners
entered the food industry back in the 1800's and are now staple in foodstuffs.
Despite their long relationship with food, sweeteners have been in the spotlights
for many reasons. Since being the perfect choice for diabetics, to the dangers
concerning toxicity, cancer and other health issues associated with their
consumption, sweeteners have come a long way. The conflicting results for the
same sweeteners and the divergent regulations are fuel for a wide debate on the
impact of sweeteners in the industry, health and lifestyle of mankind. In this
review, the history, main concerns, benefits, disadvantages, classification and
future trends are revisited for nutritive, intense and natural food additives,
while future perspectives are hypothesized.
PMID- 28689063
TI - Proanthocyanidins from Uncaria rhynchophylla induced apoptosis in MDA-MB-231
breast cancer cells while enhancing cytotoxic effects of 5-fluorouracil.
AB - Breast cancer is the most frequently diagnosed cancer and cause of cancer death
in women worldwide. Current treatments often result in systematic toxicity and
drug resistance. Combinational use of non-toxic phytochemicals with
chemotherapeutic agents to enhance the efficacy and reduce toxicity would be one
promising approach. In this study, bioactive proanthocyanidins from Uncaria
rhynchophylla (UPAs) were isolated and their anti-breast cancer effects alone and
in combination with 5- fluorouracil (5-FU) were investigated in MDA-MB-231 breast
cancer cells. The results showed that UPAs significantly inhibited cell viability
and migration ability in a dose-dependent manner. Moreover, UPAs induced
apoptosis in a dose-dependent manner which was associated with increased cellular
reactive oxygen species production, loss of mitochondrial membrane potential,
increases of Bax/Bcl-2 ratio and levels of cleaved caspase 3. Treatments of the
cells with UPAs resulted in an increase in G2/M cell cycle arrest. Cytotoxic
effects of 5-FU against MDA-MB-231 cells were enhanced by UPAs. The combination
treatment of UPAs and 5-FU for 48 h elicited a synergistic cytotoxic effect on
MDA-MB-231 cells. Altogether, these data suggest that UPAs are potential
therapeutic agents for breast cancer.
PMID- 28689064
TI - Transfer of zearalenone to the reproductive system of female rainbow trout
spawners: A potential risk for aquaculture and fish consumers?
AB - To investigate whether ZEN transfers from the alimentary tract of fish to the
somatic cells of ovaries or the oocytes, mature females of rainbow trout were
orally exposed to ZEN at a dose of 1 mg.kg-1 body mass. At sampling times of 2,
6, 12, 24, 48, and 96 h, tissues of the fish (intestine, liver, ovaries, oocytes,
muscles, and plasma) were extracted to determine the concentration of ZEN and its
metabolites using immunoaffinity columns and HPLC-FLD. Our results confirm that
ZEN is transferred from the alimentary tract to the reproductive system of the
fish, and indicate that the mycotoxin concentrates in the somatic cells of the
ovaries. Importantly, ZEN transferred to the fishes' oocytes and muscles only to
a limited extent. Our additional survey of fish hatcheries and local stores
indicated only trace amounts of ZEN residuals in the samples that were collected
in Poland and Norway between 2013 and 2015, which probably reflects good hygienic
conditions for the feed used in these hatcheries. Furthermore, our results
indicate that the health risk from dietary intake of ZEN from fish roe is
negligible. However, the potential of ZEN to transfer to the fish ovaries may be
of concern for aquaculture.
PMID- 28689065
TI - Improve the anticancer potency of the platinum(II) complexes through
functionalized leaving group.
AB - Two platinum(II) complexes with 3,3-dimethoxycyclobutane-1,1-dicarboxylate as a
leaving group were synthesized and spectrally characterized. In vitro
cytotoxicity study on these complexes indicated that complex 2 showed
considerable cytotoxicity against the tested cell lines. Notably, the higher
antiproliferative activity of complex 2 relative to the corresponding parent
compound [Pt(dach)(CBDCA)] demonstrated that the introduction of two methoxy
groups in the 1,1-cyclobutanedicarboxylate (CBDCA) can improve the anticancer
activity of the resulting platinum(II) complexes. Moreover, cellular
accumulations of complexes 1 and 2 were slightly higher than those of their
parent compounds carboplatin and Pt(dach)(CBDCA), respectively. Flow cytometry
study revealed that complexes 1 and 2 produced death of tumor cells through an
apoptotic pathway. Comparison of the chemical reactivity of Pt(dach)(CBDCA) and
complex 2 with biologically relevant nucleophiles (l-Met and thiourea) via a
kinetic method were studied by UV-Vis technique. The results showed that the
reaction rates of complex 2 with nucleophiles were faster than that of
Pt(dach)(CBDCA). DFT calculations showed that Pt(dach)(CBDCA) has slightly higher
activation energies than complex 2 for the studied reactions. Overall, the
introduction of two methoxy groups to the skeleton of 1,1
cyclobutanedicarboxylate can not only change the kinetic reactivity of the
resulting platinum(II) complexes, but also enhance their anticancer efficacy.
PMID- 28689066
TI - Roles of a mitochondrial AccSCO2 gene from Apis cerana cerana in oxidative stress
responses.
AB - In eukaryotes, cytochrome c oxidase (COX) is a multimeric protein complex that is
the last enzyme in the respiratory electron transport chain of mitochondria.
Syntheses of cytochrome c oxidase (SCO) proteins are copper-donor chaperones
involved in metalation of the CuA redox center of COX. However, its other precise
actions are not yet understood. Here, we report the characterization of AccSCO2
from Apis cerana cerana (Acc). Our data showed that AccSCO2 expression was
induced by cold (4 degrees C), CdCl2, HgCl2, ultraviolet (UV) light, and H2O2 and
was inhibited by different pesticide treatments. In addition, a disc diffusion
assay of recombinant AccSCO2, AccSCO2-R1, and AccSCO2-R2 proteins showed that
they played a functional role in protecting cells from oxidative stress involved
in copper-dependent manner. Further, following knockdown of AccSCO2 in A. cerana
cerana using RNA interference (RNAi), the expression levels of most antioxidant
genes (AccGSTD, AccGSTO1, AccGSTS4, AccSOD1, AccSOD2, etc.) were significantly
decreased in the AccSCO2-silenced bees compared with the control bees. Moreover,
the antioxidant enzymatic activities of superoxide dismutase (SOD), peroxidase
(POD) and catalase (CAT) were all lower in the silenced bees than in the control
bees. Finally, the in vivo activity of COX was measured after AccSCO2 knockdown,
which revealed a strong reduction in COX activity in the silenced bees. Thus, we
hypothesize that AccSCO2 plays important roles in cellular stress responses and
anti-oxidative processes, which help to regulate the production of mitochondrial
reactive oxygen species and/or the impairment of mitochondrial activity under
oxidative stress.
PMID- 28689067
TI - Individual variation in plasma oxytocin and vasopressin levels in relation to the
development of combat-related PTSD in a large military cohort.
AB - In an attempt to decrease the risk of developing mental health problems after
military deployment, it is important to find biological markers to identify those
at risk. Oxytocin (OT) and arginine vasopressin (AVP) are potential biomarkers
for the development of posttraumatic stress disorder (PTSD) because they are
involved in the regulation of stress and anxiety. Therefore, the aim was to
examine whether plasma OT (pOT) and AVP (pAVP) levels before and after deployment
are biomarkers for the development of posttraumatic stress symptoms over time in
addition to other known risk factors. This study is part of a large prospective
cohort study on candidate markers for stress-related mental health symptoms and
resiliency after deployment to a combat zone; Prospective Research in Stress
related Military Operations (PRISMO; N = 907). Data was collected prior to
deployment and follow-ups were performed at 1 and 6 months, and 1, 2, and 5 years
post-deployment. Blood samples were collected in the first three assessments. The
levels of pOT and pAVP were not significantly related to the development of PTSD
symptoms over time. The results confirm that age, the experience of early life
trauma, combat-related stressors and the presence of depressive symptoms are
predictive for the development of PTSD symptoms over time. These findings showed
that peripherally measured OT and AVP currently do not qualify as useful
susceptibility biomarkers for the development of PTSD symptoms over time in
military men after combat.
PMID- 28689068
TI - Efficient induction of inner ear hair cell-like cells from mouse ES cells using
combination of Math1 transfection and conditioned medium from ST2 stromal cells.
AB - We sought to establish a more efficient technique for induction of inner ear hair
cell-like cells (HC-like cells) from embryonic stem cells (ES cells) by using a
combination of two previously reported methods; ST2 stromal cell-conditioned
medium, known to be favorable for HC-like cell induction (HIST2 method), and ES
cells with transfer of the Math1 gene (Math1-ES cells). Math1-ES cells carrying
Tet-inducible Math1 were cultured for 14days with doxycycline in conditioned
medium from cultures of ST2 stromal cells following formation of 4-day embryoid
bodies (EBs). Although each of the previously introduced methods have been
reported to induce approximately 20% HC-like cells and 10% HC-like cells in their
respective populations in EB outgrowths at the end of the culture periods, the
present combined method was able to generate approximately 30% HC-like cells
expressing HC-related markers (myosin6, myosin7a, calretinin, alpha9AchR, Brn3c),
which showed remarkable formation of stereocilia-like structures. Analysis of
expressions of marker genes specific for cochlear (Lmod3, Emcn) and vestibular
(Dnah5, Ptgds) cells indicated that our HIST2 method may lead to induction of
cochlear- and vestibular-type cells. In addition, continuous Math1 induction by
doxycycline without use of the HIST2 method preferentially induced cochlear
markers with negligible effects on vestibular marker induction.
PMID- 28689069
TI - The protective role of vitamin E on Oreochromis niloticus exposed to ZnONP.
AB - The present study evaluated if ZnONPs induce oxidative stress, immunological
impairment and cellular damage in tilapia (Oreochromis niloticus), as well as the
possible protective effect of vitamin E. Fish were fed for ten days and five
study groups were investigated: controls, two ZnONPs concentrations (1.5 and
2.5mgL-1) and 1.5 and 2.5mgL-1 of ZnONPs + vitamin E (500mgkg-1 of food). O.
niloticus treated with ZnONPs, showed decreased health in comparison with the
control group and the groups that combined nanoparticles and vitamin E
supplemented diet. ZnONPs caused cell impairment by increasing ALT, AST and ALP
activity and generated oxidative stress by inhibiting SOD and CAT activity.
Biochemical changes of these biomarkers were prevented by vitamin E, although
this compound did not confer complete protection. In conclusion, ZnONPs are toxic
to O. niloticus, affecting antioxidant defenses, with vitamin E acting
protectively against this toxic effect.
PMID- 28689070
TI - Biosurfactant production from Pseudomonas taiwanensis L1011 and its application
in accelerating the chemical and biological decolorization of azo dyes.
AB - Dye dispersion and the interaction efficiency between azoreductases and dye
molecules are rate-limiting steps for the decolorization of azo dyes. In this
study, a biosurfactant-producing strain, Pseudomonas taiwanensis L1011, was
isolated from crude oil. To increase the yield of the biosurfactant BS-L1011 from
P. taiwanensis L1011, culture conditions were optimized including temperature,
initial pH, carbon source, nitrogen source and C/N ratio. A maximum yield of
1.12g/L of BS-L1011 was obtained using D-mannitol as carbon source and yeast
extract/urea as compound nitrogen source with C/N ratio of 10/4, pH 7.0 and 28
degrees C. BS-L1011 exhibited a low critical micelle concentration (CMC) of
10.5mg/L and was able to reduce the surface tension of water to 25.8+/-0.1 mN/m.
BS-L1011 was stable over a wide range of temperatures, pH values and salt
concentrations. The biosurfactant is reported for the first time to accelerate
chemical decolorization of Congo red by sodium hypochlorite, and biological
decolorization of Amaranth by Bacillus circulans BWL1061, thus showing a
potential in the treatment of dyeing wastewater.
PMID- 28689072
TI - Nucleolytic degradation of 3'-ending overhangs is essential for DNA-end resection
in RecA-loading deficient recB mutants of Escherichia coli.
AB - Degradation of a 5'-ending strand is the hallmark of the universal process of DNA
double strand break (DSB) resection, which results in creation of the central
recombination intermediate, a 3'-ending overhang. Here we show that in
Escherichia coli recB1080/recB1067 mutants, which are devoid of RecBCD's nuclease
and RecA loading activities, degradation of the unwound 3' tail is as essential
as is degradation of its 5'-ending complement. Namely, a synergistic action of
ExoI, ExoVII, SbcCD and ExoX single-strand specific exonucleases (ssExos) of 3'
5' polarity was essential for preserving cell viability, DNA repair and
homologous recombination in the recB1080/recB1067 mutants, to the same extent as
the redundant action of 5'-tail trimming ssExos RecJ and ExoVII. recB1080
derivatives lacking 3'-5' ssExos also showed a strong induction of the SOS
response and greatly increased SOS-dependent mutagenesis. Furthermore, we show
that ExoI and ExoVII ssExos act synergistically in suppressing illegitimate
recombination in the recB1080 mutant but not in a wt strain, while working in
concert with the RecQ helicase. Remarkably, 3'-5' ssExos show synergism with RecQ
helicase in the recB1080 mutant in all the assays tested. The effect of
inactivation of 3'-5' ssExos in the recB1080/recB1067 mutants was much stronger
than in wt, recD, and recB strains. These results demonstrate that the presence
of a long, reactive 3' overhang can be as toxic for a cell as its complete
absence, i.e. it may prevent DSB repair. Our results indicate that coupling of
helicase and RecA-loading activity during dsDNA-end resection is crucial in
avoiding the deleterious effects of a long and stabile 3' tail in E. coli.
PMID- 28689073
TI - Endocrine-related adverse events associated with immune checkpoint blockade and
expert insights on their management.
AB - Agents that modulate immune checkpoint proteins, such as cytotoxic T-lymphocyte
antigen-4 (CTLA-4) and programmed death receptor-1 (PD-1), have become a mainstay
in cancer treatment. The clinical benefit afforded by immune checkpoint
inhibitors can be accompanied by immune-related adverse events (irAE) that affect
the skin, gastrointestinal tract, liver, and endocrine system. The types of irAEs
associated with immune checkpoint inhibitors are generally consistent across
tumor types. Immune-related endocrine events can affect the pituitary, thyroid,
and adrenal glands, as well as other downstream target organs. These events are
unique when compared with other irAEs because the manifestations are often
irreversible. Immune-related endocrine events are typically grade 1/2 in severity
and often present with non-specific symptoms, making them difficult to diagnose.
The mechanisms underlying immune-related target organ damage in select
individuals remain mostly undefined. Management includes close patient
monitoring, appropriate laboratory testing for endocrine function, replacement of
hormones, and consultation with an endocrinologist when appropriate. An awareness
of the symptoms and management of immune-related endocrine events may aid in the
safe and appropriate use of immune checkpoint inhibitors in clinical practice.
PMID- 28689074
TI - A label-free fluorimetric detection of biothiols based on the oxidase-like
activity of Ag+ ions.
AB - In this work, a label-free and sensitive fluorimetric method has been developed
for the detections of biothiols including cysteine (Cys), homocysteine (Hcy), and
glutathione (GSH), based on the specific biothiol-induced inhibition of the
oxidase-like activity of silver ions (Ag+). It is well established that o
phenylenediamine (OPD) can be oxidized by Ag+ ions to generate fluorescent 2,3
diaminophenazine (OPDox). The introduction of biothiols would inhibit the
oxidation of OPD by Ag+ due to the strong coordination between biothiols and Ag+.
The changes of fluorescence intensities obtained in the Ag+-OPD system exhibited
good linear correlations in the ranges of 0.50-30.0MUM for Cys, 1.0-45.0MUM for
Hcy and 0.50-40.0MUM for GSH. The detection limits (S/N=3) of Cys, Hcy and GSH
were 110nM, 200nM and 150nM, respectively. Subsequently, the developed
fluorimetric method was successfully applied for the detection of biothiols in
human serum.
PMID- 28689071
TI - Sexual assault victimization and psychopathology: A review and meta-analysis.
AB - Sexual assault (SA) is a common and deleterious form of trauma. Over 40years of
research on its impact has suggested that SA has particularly severe effects on a
variety of forms of psychopathology, and has highlighted unique aspects of SA as
a form of trauma that contribute to these outcomes. The goal of this meta
analytic review was to synthesize the empirical literature from 1970 to 2014
(reflecting 497 effect sizes) to understand the degree to which (a) SA confers
general risk for psychological dysfunction rather than specific risk for
posttraumatic stress, and (b) differences in studies and samples account for
variation in observed effects. Results indicate that people who have been
sexually assaulted report significantly worse psychopathology than unassaulted
comparisons (average Hedges' g=0.61). SA was associated with increased risk for
all forms of psychopathology assessed, and relatively stronger associations were
observed for posttraumatic stress and suicidality. Effects endured across
differences in sample demographics. The use of broader SA operationalizations
(e.g., including incapacitated, coerced, or nonpenetrative SA) was not associated
with differences in effects, although including attempted SA in
operationalizations resulted in lower effects. Larger effects were observed in
samples with more assaults involving stranger perpetrators, weapons, or physical
injury. In the context of the broader literature, our findings provide evidence
that experiencing SA is major risk factor for multiple forms of psychological
dysfunction across populations and assault types.
PMID- 28689075
TI - Anharmonic vibrational spectra and mode-mode couplings analysis of 2
aminopyridine.
AB - Vibrational spectra of 2-aminopyridine (2AP) have been analyzed using the
vibrational self-consistence field theory (VSCF), correlated corrected
vibrational self-consistence field theory (CC-VSCF) and vibrational perturbation
theory (VPT2) at B3LYP/6-311G(d,p) framework. The mode-mode couplings affect the
vibrational frequencies and intensities. The coupling integrals between pairs of
normal modes have been obtained on the basis of quartic force field (2MR-QFF)
approximation. The overtone and combination bands are also assigned in the FTIR
spectrum with the help of anharmonic calculation at VPT2 method. A statistical
analysis of deviations shows that estimated anharmonic frequencies are closer to
the experiment over harmonic approximation. Furthermore, the anharmonic
correction has also been carried out for the dimeric structure of 2AP. The
fundamental vibration bands have been assigned on the basis of potential energy
distribution (PED) and visual look over the animated modes. Other important
molecular properties such as frontier molecular orbitals and molecular
electrostatics potential mapping have also been analyzed.
PMID- 28689076
TI - Near-near-infrared thermal lens spectroscopy to assess overtones and combination
bands of sulfentrazone pesticide.
AB - Thermal lens spectroscopy (TLS) in the near-near-infrared region was used to
explore the absorptions of overtones and combination bands of sulfentrazone (SFZ)
herbicide diluted in methanol. This spectroscopic region was chosen in order to
guarantee that only thermal lens effect is noted during the experimental
procedure. The results showed that it was possible to detect very low
concentrations (~2ng/MUL) of SFZ in methanol by determining its thermal
diffusivity or the absorption coefficient due to the 3nu(NH)+1delta(CH)
combination band. This minimum SFZ concentration is the limit observed by
chromatography method. The findings demonstrated that the TLS can be used for
precise and accurate assessment of pesticides in ecosystems. Besides, the
3nu(NH)+1delta(CH) combination band at 960nm can be used as a marker for SFZ in
methanol.
PMID- 28689077
TI - ATR-IR study of skin components: Lipids, proteins and water. Part I: Temperature
effect.
AB - In this work we report the studies of the effect of temperature on skin
components, such as lipids, proteins and water. Modifications of lipids structure
induced by increasing temperature (from 20 to 90 degrees C) have been studied
using ATR-IR (Attenuated Total Reflectance Infrared) spectroscopy, which is a
powerful tool for characterization of the molecular structure and properties of
tissues, such as skin. Due to the small depth of penetration (0.6-5.6MUm), ATR-IR
spectroscopy probes only the outermost layer of the skin, i.e. the stratum
corneum (SC). The assignment of main spectral features of skin components allows
for the determination of phase transitions from the temperature dependencies of
band intensities [e.g. nuas(CH2) and nus(CH2)]. The phase transitions were
determined by using two methods: the first one was based on the first derivative
of the Boltzmann function and the second one employed tangent lines of sigmoidal,
aforementioned dependencies. The phase transitions in lipids were correlated with
modifications of the structure of water and proteins.
PMID- 28689078
TI - Selective biosensing of Staphylococcus aureus using chitosan quantum dots.
AB - Selective biosensing of Staphylococcus aureus (S. aureus) using chitosan modified
quantum dots (CTS@CdS QDs) in the presence of hydrogen peroxide is reported. The
method is based on the intrinsic positive catalase activity of S. aureus. CTS@CdS
quantum dots provide high dispersion in aqueous media with high fluorescence
emission. Staphylococcus aureus causes a selective quenching of the fluorescence
emission of CTS@CdS QDs in the presence of H2O2 compared to other pathogens such
as Escherichia coli and Pseudomonas aeruginosa. The intrinsic enzymatic character
of S. aureus (catalase positive) offers selective and fast biosensing. The
present method is highly selective for positive catalase species and requires no
expensive reagents such as antibodies, aptamers or microbeads. It could be
extended for other species that are positive catalase.
PMID- 28689079
TI - Different molecular organization of two carotenoids, lutein and zeaxanthin, in
human colon epithelial cells and colon adenocarcinoma cells.
AB - Two cell lines, human normal colon epithelial cells (CCD 841 CoTr) and human
colon adenocarcinoma cells (HT-29) were cultured in the presence of exogenous
carotenoids, either zeaxanthin or lutein. Both carotenoids demonstrated
cytotoxicity with respect to cancer cells but not to normal cells. Cells from
both the cell lines were analyzed with application of fluorescence lifetime
imaging microscopy and Raman scattering microscopy. Both imaging techniques show
effective incorporation of carotenoid molecules into growing cells. Comparison of
the Raman scattering and fluorescence lifetime characteristics reveals different
molecular organization of carotenoids in the carcinoma and normal cells. The main
difference consists in a carotenoid aggregation level which is substantially
lower in the carcinoma cells as compared to the normal cells. Different molecular
organization of carotenoids was interpreted in terms of a different metabolism of
normal and carcinoma cells and has been concluded to provide a possibility of
cancer diagnosis based on spectroscopic analyses.
PMID- 28689080
TI - 3D reconstruction of the magnetic vector potential using model based iterative
reconstruction.
AB - Lorentz transmission electron microscopy (TEM) observations of magnetic
nanoparticles contain information on the magnetic and electrostatic potentials.
Vector field electron tomography (VFET) can be used to reconstruct
electromagnetic potentials of the nanoparticles from their corresponding LTEM
images. The VFET approach is based on the conventional filtered back projection
approach to tomographic reconstructions and the availability of an incomplete set
of measurements due to experimental limitations means that the reconstructed
vector fields exhibit significant artifacts. In this paper, we outline a model
based iterative reconstruction (MBIR) algorithm to reconstruct the magnetic
vector potential of magnetic nanoparticles. We combine a forward model for image
formation in TEM experiments with a prior model to formulate the tomographic
problem as a maximum a-posteriori probability estimation problem (MAP). The MAP
cost function is minimized iteratively to determine the vector potential. A
comparative reconstruction study of simulated as well as experimental data sets
show that the MBIR approach yields quantifiably better reconstructions than the
VFET approach.
PMID- 28689081
TI - High-throughput, semi-automated quantitative STEM mass measurement of supported
metal nanoparticles using a conventional TEM/STEM.
AB - The adaptation of quantitative STEM techniques to enable atom-counting in
supported metal nanoparticles with a modern, conventional (non-aberration
corrected) TEM/STEM (a JEOL JEM2100F) without the need for any modifications or
special hardware is presented. No image simulation is required, either. This
technique enables the practical analysis of the size, mass, and basic shape
information of statistically robust populations of hundreds to thousands of
nanoparticles. The methods for performing the necessary calibrations of the
microscope and images are detailed. A user-friendly semi-automated analysis
program was also written to facilitate high throughput. The program optimizes the
analysis parameters, applying the procedure consistently across the entire
dataset, enhancing the meaningfulness of the statistics as well as the
reproducibility and transferability of the results. A series of atomically
precise Au nanoparticles were used to validate the technique, which was
determined to be accurate within a (nearly uniform) scaling factor of around two
for the given instrument, and could be brought into better agreement with a
calibration standard. The magnitude of the disparity was found to significantly
and unexpectedly rely on the chosen magnification and spot size, the underlying
reasons for which are unclear and likely instrument-dependent. The possible
sources of error from the calibration and acquisition were examined and their
impact on the accuracy and precision of quantification were estimated. The
scattering cross-sections measured using this technique are relatively
insensitive to moderate errors in the various detector calibrations but
particularly sensitive to pixel size error.
PMID- 28689082
TI - Origin of atomic displacement in HAADF image of the tilted specimen.
AB - The effect of the tilt of the crystallographic orientation with respect to an
incident electron probe on high-angle annular dark field (HAADF) imaging in
aberration-corrected scanning transmission electron microscopy (STEM) is
investigated in experiment and simulation. A small specimen tilt can lead to
unequal deviations of different atom species in the HAADF image and result in
further relative displacement between anion and cation. Simulated HAADF images
also confirm that the crystal tilt causes an artifact in atom polarization. The
effect is derived from the scattering abilities of different atoms.
PMID- 28689083
TI - Management of hereditary antithrombin deficiency in pregnancy.
AB - Antithrombin (AT) deficiency is a high-risk thrombophilia and a rare condition.
Despite full anticoagulation during pregnancy and the postpartum period, women
with AT deficiency may still be vulnerable to developing venous thromboembolism
(VTE), including fatal events. There is limited guidance on the management of AT
deficiency in pregnancy, including the role of AT concentrates. Following a
comprehensive review of the state of the art with respect to recommendations and
guidelines, our expert panel in maternal-fetal medicine, hematology and basic
science reached consensus on key issues in the recognition and management of AT
deficiency in pregnancy. This paper summarizes the state of the art and
summarizes what we believe are best practices with special emphasis on a
multidisciplinary approach involving obstetrics and hematology in the care of
women with AT deficiency.
PMID- 28689084
TI - Regional variations in frequency of glycosylated hemoglobin (HbA1c) monitoring in
Korea: A multilevel analysis of nationwide data.
AB - PURPOSE: Suboptimal frequency of glycosylated hemoglobin (HbA1c) monitoring is
associated with poor diabetes control. We aimed to analyze compliance to HbA1c
testing guidelines and explore associated individual and area-level determinants,
focusing on regional variation. METHODS: This cross-sectional study between the
period of 2012-2013 was conducted by using the Korean National Health Insurance
Research Database, and included 45,634 patients diagnosed with diabetes mellitus,
who were prescribed any anti-diabetic medications, including insulin. We
calculated the proportion of each HbA1c testing frequency (>=1, >=2, or >=4 times
per year) stratified by 17 administrative regions. Multilevel and multivariate
logistic analyses were performed with regional (proportion of farmer population)
and individual characteristics (age, sex, income level, duration of diabetes, and
most visited medical institution). RESULTS: Overall, 67.3% of the patients
received>=1 HbA1c test per year; 37.8% and 6.1% received >=2 and >=4 tests per
year, respectively. Those managed in secondary-level hospitals or clinics and
those living in rural areas were less likely to receive HbA1c testing. Even after
adjusting for individual and regional level characteristics, significant area
level variation was observed (variance participant coefficients were 7.91%,
9.58%, and 14.43% for testing frequencies of >=1, >=2, and >=4 times a year,
respectively). CONCLUSIONS: The frequency of HbA1c monitoring is suboptimal in
Korea, especially in rural areas. Moreover, significant regional variation was
observed, implying a contextual effect. This suggests the need for developing
policy actions to improve HbA1c monitoring. In particular, access to HbA1c
testing in rural primary care clinics must be improved.
PMID- 28689085
TI - Identification and characterization of a naturally occurring, efficiently
cleaved, membrane-bound, clade A HIV-1 Env, suitable for immunogen design, with
properties comparable to membrane-bound BG505.
AB - Efficient cleavage of HIV-1 Env gp160 into its constituent subunits correlates
with selective binding to neutralizing antibodies and are the closest mimetic of
native, functional Envs. This was first demonstrated with the clade B Env, JRFL.
The correlation between efficient cleavage and selective binding to neutralizing
antibodies is the guiding principle for immunogen design for HIV vaccine. We have
recently reported that Envs 4-2.J41 (clade C) and JRCSF (clade B) are also
efficiently cleaved and show similar properties. However, an efficiently cleaved,
membrane-bound clade A Env suitable for genetic vaccination has not been directly
demonstrated. Here we report that BG505 and a new clade A Env, QB726.70M.ENV.C4
(or A5) are efficiently cleaved on cell membrane. A5 shows desirable antigenic
properties comparable with BG505 on cell surface. A5SOSIP in supernatant displays
majority of bNAb binding epitopes. Thus, both BG505 and A5 Envs can be used in
DNA prime-protein boost vaccination studies.
PMID- 28689086
TI - Validation of reference genes for quantifying changes in gene expression in virus
infected tobacco.
AB - To facilitate quantification of gene expression changes in virus-infected tobacco
plants, eight housekeeping genes were evaluated for their stability of expression
during infection by one of three systemically-infecting viruses (cucumber mosaic
virus, potato virus X, potato virus Y) or a hypersensitive-response-inducing
virus (tobacco mosaic virus; TMV) limited to the inoculated leaf. Five reference
gene validation programs were used to establish the order of the most stable
genes for the systemically-infecting viruses as ribosomal protein L25 > beta
Tubulin > Actin, and the least stable genes Ubiquitin-conjugating enzyme (UCE) <
PP2A < GAPDH. For local infection by TMV, the most stable genes were EF1alpha >
Cysteine protease > Actin, and the least stable genes were GAPDH < PP2A < UCE.
Using two of the most stable and the two least stable validated reference genes,
three defense responsive genes were examined to compare their relative changes in
gene expression caused by each virus.
PMID- 28689087
TI - The histone deacetylase inhibitor SAHA simultaneously reactivates HIV-1 from
latency and up-regulates NKG2D ligands sensitizing for natural killer cell
cytotoxicity.
AB - In pilot HIV-1 eradication studies, patients' immune responses were ineffective
at killing viral reservoirs reactivated through latency reversing agents (LRAs)
like suberoylanilide hydroxamic acid (SAHA). We hypothesized that T cells
harboring reactivated HIV-1 express MIC and ULBP ligands for the activating NKG2D
receptor of natural killer (NK) cells. Here, we demonstrated that MICA/B and
ULBP2 are induced by SAHA on primary T cells harboring reactivated virus. Using
latently HIV-1-infected J-Lat 6.3/8.4/9.2 and J1.1 cell lines, we showed that
SAHA reverts latency and, simultaneously, up-regulates MICA/B and ULBP2 acting at
the transcriptional level and through ATR activation, thus sensitizing T cells
with reactivated virus to NKG2D-mediated killing by NK cells. Moreover, IL-2 and
IL-15 potently boosted NKG2D expression and cytotoxicity of NK cells against SAHA
reactivated p24+ target cells. Therefore, immunotherapy with cytokines enhancing
NKG2D-mediated NK-cell cytotoxicity combined with administration of LRAs up
modulating NKG2D ligands, represents a promising approach towards HIV-1
eradication.
PMID- 28689088
TI - Looking for ideas: Eye behavior during goal-directed internally focused
cognition.
AB - Humans have a highly developed visual system, yet we spend a high proportion of
our time awake ignoring the visual world and attending to our own thoughts. The
present study examined eye movement characteristics of goal-directed internally
focused cognition. Deliberate internally focused cognition was induced by an idea
generation task. A letter-by-letter reading task served as external task. Idea
generation (vs. reading) was associated with more and longer blinks and fewer
microsaccades indicating an attenuation of visual input. Idea generation was
further associated with more and shorter fixations, more saccades and saccades
with higher amplitudes as well as heightened stimulus-independent variation of
eye vergence. The latter results suggest a coupling of eye behavior to internally
generated information and associated cognitive processes, i.e. searching for
ideas. Our results support eye behavior patterns as indicators of goal-directed
internally focused cognition through mechanisms of attenuation of visual input
and coupling of eye behavior to internally generated information.
PMID- 28689089
TI - A qualitative study of barriers and facilitators in treating drug use among
Israeli mothers: An intersectional perspective.
AB - RATIONALE: Despite the benefits and availability of drug treatment in Western
countries, research has shown low utilisation rates, especially by mothers.
Studies have indicated internal barriers (e.g., shame) and external/structural
barriers (e.g., poverty) to women's utilisation of drug treatment, but little is
known about the interrelated axes of marginalization that create such barriers
and, even less, facilitators of treatment. A promising avenue for examining this
path may be the theoretical perspective of intersectionality, which has often
been used to illustrate how women's experiences are shaped by gender in
conjunction with other factors, including class, age, and race. OBJECTIVE: The
purpose of the study was to obtain a deeper understanding of the barriers and
facilitators of drug-abuse treatment among substance-abusing mothers, including
practical implications. METHODS: In-depth interviews were conducted with 25
Israeli-born and immigrant mothers known to child protection and welfare
agencies. A critical feminist theoretical perspective informed by
intersectionality was adopted to examine the barriers to and facilitators of
their enrolment in drug treatment. RESULTS: Thematic analysis revealed three
themes in the interrelationships of different factors and treatment utilisation.
First, the threat of losing child custody was interrelated with lack of social
and family support, immigration status, being post-partum, and economic hardship
to shape barriers to treatment. Second, a set of coping resources originating in
their marginality was interrelated with opportunity for treatment. Last, the
participants suggested changes that would encourage treatment utilisation, with
focus on non-judgmental referral procedures. CONCLUSIONS: The findings indicated
that barriers and facilitators are interrelated and co-constructed, reflecting
the interlocking of power and oppression across the axes of class, gender, and
ethnicity. Focusing on social inequality and gender in policies and research on
women's drug treatment, the findings may inform the development of strategies to
overcome treatment barriers.
PMID- 28689090
TI - Social and emotional wellbeing assessment instruments for use with Indigenous
Australians: A critical review.
AB - RATIONALE: There is growing recognition that in addition to universally
recognised domains and indicators of wellbeing (such as population health and
life expectancy), additional frameworks are required to fully explain and measure
Indigenous wellbeing. In particular, Indigenous Australian wellbeing is largely
determined by colonisation, historical trauma, grief, loss, and ongoing social
marginalisation. Dominant mainstream indicators of wellbeing based on the
biomedical model may therefore be inadequate and not entirely relevant in the
Indigenous context. It is possible that "standard" wellbeing instruments fail to
adequately assess indicators of health and wellbeing within societies that have a
more holistic view of health. OBJECTIVE: The aim of this critical review was to
identify, document, and evaluate the use of social and emotional wellbeing
measures within the Australian Indigenous community. METHOD: The instruments were
systematically described regarding their intrinsic properties (e.g., generic v.
disease-specific, domains assessed, extent of cross-cultural adaptation and
psychometric characteristics) and their purpose of utilisation in studies (e.g.,
study setting, intervention, clinical purpose or survey). We included 33 studies,
in which 22 distinct instruments were used. RESULTS: Three major categories of
social and emotional wellbeing instruments were identified: unmodified standard
instruments (10), cross-culturally adapted standard instruments (6), and
Indigenous developed measures (6). Recommendations are made for researchers and
practitioners who assess social and emotional wellbeing in Indigenous
Australians, which may also be applicable to other minority groups where a more
holistic framework of wellbeing is applied. CONCLUSION: It is advised that
standard instruments only be used if they have been subject to a formal cross
cultural adaptation process, and Indigenous developed measures continue to be
developed, refined, and validated within a diverse range of research and clinical
settings.
PMID- 28689092
TI - Induction chemotherapy for nasopharyngeal cancer: An eternally unfinished issue?
PMID- 28689093
TI - Immune checkpoint inhibitors and elderly people: A review.
AB - Immune checkpoint inhibitors, including targeting programmed cell death 1,
programmed cell death ligand 1, and cytotoxic T lymphocyte antigen 4 pathways,
are a new type of cancer treatment. This approach of targeting the immune system
has demonstrated dramatic efficacy for several cancers, and various drugs have
been approved by health authorities and are used in clinical practice. Elderly
patients (>=65 years) represent most of the cancers diagnosed and deaths by age
group, with an increase expected over the next decade. However, this subgroup of
patients is under-represented in clinical trials. Ageing is also associated with
a decrease in the effectiveness of the immune system and in alterations to it.
Few specific trials have been carried out for immunotherapy in elderly people,
with most patients considered to be fit. In this review, we discuss the impact of
ageing and immunosenescence on immune system functions, and we assess the safety
and efficacy of immune checkpoint inhibitors in elderly patients, principally
from the data of pivotal clinical trials with subgroup analysis. Tolerance in
elderly patients seems similar to younger people, but efficacy seems different
between younger and elderly patients according to the type of cancer, some
showing no difference and others less efficacy in the elderly subgroup. However,
the numbers in elderly groups are small and more investigation is needed, with
specific clinical trials for elderly cancer patients.
PMID- 28689091
TI - Geographical variability in survival of European children with central nervous
system tumours.
AB - Survival for childhood central nervous system (CNS) tumours varies across Europe,
partly because of the difficulty of distinguishing malignant from non-malignant
disease. This study examines bias in CNS tumours survival analysis to obtain the
reliable and comparable survival figures. We analysed survival data for about
15,000 children (age <15) diagnosed with CNS between 2000 and 2007, from 71
population-based cancer registries in 27 countries. We selected high-quality data
based on registry-specific data quality indicators and recorded observed 1-year
and 5-year survival by countries and CNS entity. We provided age-adjusted
survival and used a Cox model to calculate the hazard ratios (HRs) of death,
adjusting by age, site and grading by country. Recording of non-malignant
lesions, use of appropriate morphology codes and completeness of life status
follow-up differed among registries. Five-year survival by countries varied less
when non-malignant tumours were included, with rates between 79.5% and 42.8%. The
HRs of dying, for registries with good data, adjusting by age and grading, were
between 0.7 and 1.2; differences were similar when site (supra- and infra
tentorial) was included. Several sources of bias affect the correct definition of
CNS tumours, the completeness of incidence series and the goodness of follow-up.
The European Network of Cancer Registries needs to improve childhood cancer
registration and stress the need to update the International Classification for
Cancer. Since survival differences persisted even when restricting the analysis
to registries with satisfactory data, and since diagnosis of CNS tumours is
difficult and treatment complex, national plans must aim for the revision of the
diagnosis and the coordination of care, with adequate national and international
networks.
PMID- 28689094
TI - Recurrent bowel obstruction: unusual presentation of pembrolizumab-induced
pancreatitis in annular pancreas.
PMID- 28689095
TI - First dual AK/GSK-3beta inhibitors endowed with antioxidant properties as
multifunctional, potential neuroprotective agents.
AB - The manuscript deals with the design, synthesis and biological evaluation of
novel benzoxazinone-based and indole-based compounds as multifunctional
neuroprotective agents. These compounds inhibit human adenosine kinase (hAK) and
human glycogen synthase kinase 3 beta (hGSK-3beta) enzymes. Computational
analysis based on a molecular docking approach underlined the potential
structural requirements for simultaneously targeting both proteins' allosteric
sites. In silico hints drove the synthesis of appropriately decorated
benzoxazinones and indoles (5a-s, and 6a-c) and biochemical analysis revealed
their behavior as allosteric inhibitors of hGSK-3beta. For both our hit 4 and the
best compounds of the series (5c,l and 6b) the potential antioxidant profile was
assessed in human neuroblastoma cell lines (IMR 32, undifferentiated and neuronal
differentiated), by evaluating the protective effect of selected compounds
against H2O2 cytotoxicity and reactive oxygen species (ROS) production. Results
showed a strong efficacy of the tested compounds, even at the lower doses, in
counteracting the induced oxidative stress (50 MUM of H2O2) and in preventing ROS
formation. In addition, the tested compounds did not show any cytotoxic effect
determined by the LDH release, at the concentration range analyzed (from 0.1 to
50 MUM). This study allowed the identification of compound 5l, as the first dual
hAK/hGSK-3beta inhibitor reported to date. Compound 5l, which behaves as an
effective antioxidant, holds promise for the development of new series of
potential therapeutic agents for the treatment of neurodegenerative diseases
characterized by an innovative pharmacological profile.
PMID- 28689096
TI - Discovery of phenylsulfonyl acetic acid derivatives with improved efficacy and
safety as potent free fatty acid receptor 1 agonists for the treatment of type 2
diabetes.
AB - The free fatty acid receptor 1 (FFA1) has emerged as an attractive anti-diabetic
target that mediates glucose-stimulated insulin secretion. Several FFA1 agonists
have been reported, but many of them possessed somewhat high lipophilicity and/or
molecular weight. Herein, we describe the identification of sulfone-carboxylic
acid moiety with the multiple advantages of reducing lipophilicity, cytotoxicity
and beta-oxidation associated with compound 2. Further structure-activity
relationship study based on the previleged scaffolds led to the discovery of 2
{(4-[(2'-chloro-[1,1'-biphenyl]-3-yl)methoxy]phenyl)sulfonyl}acetic acid
(compound 20), which showed a better balance than compound 2 in terms of
physicochemical properties, cytotoxicity profiles and pharmacokinetic properties.
Subsequent in vivo studies demonstrated that compound 20 robustly improves the
glucose tolerance both in normal and type 2 diabetic models without the risk of
hypoglycemia. Compared to the high risk of TAK-875 induced liver toxicity, there
was no significant adverse effects such as hepatic and renal toxicity were
observed in the chronic toxicity studies of compound 20 even at the higher dose.
PMID- 28689097
TI - Design, synthesis and antitubercular potency of 4-hydroxyquinolin-2(1H)-ones.
AB - In this study, a 50-membered library of substituted 4-hydroxyquinolin-2(1H)-ones
and two closely related analogues was designed, scored in-silico for drug
likeness and subsequently synthesized. Thirteen derivatives, all sharing a common
3-phenyl substituent showed minimal inhibitory concentrations against
Mycobacterium tuberculosis H37Ra below 10 MUM and against Mycobacterium bovis
AN5A below 15 MUM but were inactive against faster growing mycobacterial species.
None of these selected derivatives showed significant acute toxicity against MRC
5 cells or early signs of genotoxicity in the VitotoxTM assay at the active
concentration range. The structure activity study relation provided some insight
in the further favourable substitution pattern at the 4-hydroxyquinolin-2(1H)-one
scaffold and finally 6-fluoro-4-hydroxy-3-phenylquinolin-2(1H)-one (38) was
selected as the most promising member of the library with a MIC of 3.2 MUM and a
CC50 against MRC-5 of 67.4 MUM.
PMID- 28689098
TI - Evaluation of clinical and laboratory parameters used in the identification of
index cases for genetic screening of familial hypercholesterolemia in Brazil.
AB - BACKGROUND AND AIMS: There is controversy on the accuracy of different diagnostic
criteria for familial hypercholesterolemia (FH). The aim of this study is to
assess the performance of different clinical criteria used to identify
individuals for FH genetic cascade screening in Brazil. METHODS: All index cases
(IC) registered in the Hipercol Brasil program between 2011 and 2016 were
analyzed. Inclusion criteria were age >=18 years and elevated LDL-cholesterol
(LDL-C) levels, with a conclusive result in the genetic test, whether positive or
negative. Initially, we tested the multivariable association between clinical and
laboratory markers and the presence of an FH causing mutation. Then, we analyzed
sensitivity, specificity, positive and negative predictive values for the LDL-C
quartile distribution, LDL-C as a continuous variable, as well as the performance
measures for the Dutch Lipid Clinic Network (DLCN) score to identify a mutation.
RESULTS: Overall, 753 ICs were included and an FH causing mutation was found in
34% (n = 257) of the subjects. After multivariable analysis, LDL-C as a
continuous variable, tendon xanthomas and corneal arcus were independently
associated with the presence of FH mutations. LDL-C values >= 230 mg/dL (5.9
mmol/L) had the best tradeoff between sensitivity and specificity to diagnose a
mutation. The DLCN score presented a better performance than LDL-C to identify a
mutation, area under the ROC curve were 0.744 (95% CI: 0.704-0.784) and 0.730
(95% CI: 0.687-0.774), respectively, p=0.014. CONCLUSIONS: In our population, LDL
>=230 mg/dL is a feasible criterion to indicate ICs to genetic testing.
PMID- 28689099
TI - Polyethylene imine/graphene oxide layer-by-layer surface functionalization for
significantly improved limit of detection and binding kinetics of immunoassays on
acrylate surfaces.
AB - Antibody immobilization on polymeric substrates is a key manufacturing step for
microfluidic devices that implement sample-to-answer automation of immunoassays.
In this work, a simple and versatile method to bio-functionalize
poly(methylmethacrylate) (PMMA), a common material of such "Lab-on-a-Chip"
systems, is proposed; using the Layer-by-Layer (LbL) technique, we assemble
nanostructured thin films of poly(ethylene imine) (PEI) and graphene oxide (GO).
The wettability of PMMA surfaces was significantly augmented by the surface
treatment with (PEI/GO)5 film, with an 81% reduction of the contact angle, while
the surface roughness increased by 600%, thus clearly enhancing wettability and
antibody binding capacity. When applied to enzyme-linked immunosorbent assays
(ELISAs), the limit of detection of PMMA surface was notably improved from
340pgmL-1 on commercial grade polystyrene (PS) and 230pgmL-1 on plain PMMA
surfaces to 130pgmL-1 on (PEI/GO)5 treated PMMA. Furthermore, the accelerated
antibody adsorption kinetics on the LbL films of GO allowed to substantially
shorten incubation times, e.g. for anti-rat IgG adsorption from 2h down to 15min
on conventional and treated surfaces, respectively.
PMID- 28689100
TI - Synthesis and characterization of amino acid-functionalized calcium phosphate
nanoparticles for siRNA delivery.
AB - Small interfering RNAs (siRNA) are short nucleic acid fragments of about 20-27
nucleotides, which can inhibit the expression of specific genes. siRNA based RNAi
technology has emerged as a promising method for the treatment of a variety of
diseases. However, a major limitation in the therapeutic use of siRNA is its
rapid degradation in plasma and cellular cytoplasm, resulting in short half-life.
In addition, as siRNA molecules cannot penetrate into the cell efficiently, it is
required to use a carrier system for its delivery. In this work, chemically and
morphologically different calcium phosphate (CaP) nanoparticles, including
spherical-like hydroxyapatite (HA-s), needle-like hydroxyapatite (HA-n) and
calcium deficient hydroxyapatite (CDHA) nanoparticles were synthesized by the sol
gel technique and the effects of particle characteristics on the binding capacity
of siRNA were investigated. In order to enhance the gene loading efficiency, the
nanoparticles were functionalized with arginine and the morphological and their
structural characteristics were analyzed. The addition of arginine did not
significantly change the particle sizes; however, it provided a significantly
increased binding of siRNA for all types of CaP nanoparticles, as revealed by
spectrophotometric measurements analysis. Arginine functionalized HA-n
nanoparticles showed the best binding behavior with siRNA among the other
nanoparticles due to its high, positive zeta potential (+18.8mV) and high surface
area of Ca++ rich "c" plane. MTT cytotoxicity assays demonstrated that all the
nanoparticles tested herein were biocompatible. Our results suggest that high
siRNA entrapment in each of the three modified non-toxic CaP nanoparticles make
them promising candidates as a non-viral vector for delivering therapeutic siRNA
molecules to treat cancer.
PMID- 28689101
TI - Comparison of surrogate indices for insulin sensitivity with parameters of the
intravenous glucose tolerance test in early lactation dairy cattle.
AB - The aim of this study was to investigate the correlation between different
surrogate indices and parameters of the intravenous glucose tolerance test
(IVGTT) in dairy cows at the start of their lactation. Ten dairy cows underwent
IVGTT on Days 3 to 7 after calving. Areas under the curve during the 90 min after
infusion, peak and nadir concentrations, elimination rates, and times to reach
half-maximal and basal concentrations for glucose, insulin, nonesterified fatty
acids, and beta-hydroxybutyrate were calculated. Surrogate indices were computed
using the average of the IVGTT basal samples, and their correlation with the
IVGTT parameters studied through the Spearman's rank test. No statistically
significant or strong correlation coefficients (P > 0.05; |rho| < 0.50) were
observed between the insulin sensitivity measures derived from the IVGTT and any
of the surrogate indices. Therefore, these results support that the assessment of
insulin sensitivity in early lactation cattle cannot rely on the calculation of
surrogate indices in just a blood sample, and the more laborious tests (ie,
hyperinsulinemic euglycemic clamp test or IVGTT) should be employed to predict
the sensitivity of the peripheral tissues to insulin accurately.
PMID- 28689102
TI - Monthly methylprednisolone in combination with interferon beta or glatiramer
acetate for relapsing-remitting multiple sclerosis: A multicentre, single-blind,
prospective trial.
AB - OBJECTIVES: Multiple sclerosis is usually clinically characterized by repeated
subacute relapses followed by remissions. Corticosteroids are used for relapses,
and this treatment has been shown to increase the speed of recovery from these.
We aimed to evaluate the efficacy and safety of pulsed methylprednisolone given
every month as an add-on therapy to interferon beta or glatiramer acetate in
patients with relapsing-remitting multiple sclerosis. PATIENTS AND METHODS: This
was a multi-center, examiner-blinded, prospective study. Absolute annualized
relapse rates and Expanded Disability Status Scale scores were calculated.
RESULTS: 103 patients were given intravenous methylprednisolone (1 dose of 1g IV)
once a month for 12 months as add-on therapy and were assessed during this
period. The decrease in the absolute annualized relapse rate was 0.69, and 72
patients were relapse-free at the end of the year. Sixty-nine of the 103 patients
had the same Expanded Disability Status Scale scores at the end of one year,
while 21 were less disabled, and 13 sustained disability progression. Health
related quality of life measured using the MS Quality of Life scale improved
significantly during the study period. CONCLUSION: The addition of monthly pulsed
methylprednisolone to subcutaneous interferon beta or glatiramer acetate therapy
significantly reduced the relapse rate and may also be beneficial in terms of
disease progression. These combinations were also safe, and most patients
tolerated methylprednisolone as an add-on to interferon beta or glatiramer
acetate.
PMID- 28689103
TI - 123I-Meta-iodobenzylguanidine (MIBG) myocardial scintigraphy in patients showing
scans without evidence of dopaminergic deficits (SWEDDs).
AB - OBJECTIVE: Scans without evidence of dopaminergic deficits (SWEDDs) in dopamine
transporter single-photon emission computed tomography (DAT-SPECT) are found in
3.6-19.6% of patients with clinically suspected Parkinson's disease (PD). We
investigated whether combined use of 123I-meta-iodobenzylguanidine (MIBG)
myocardial scintigraphy would be helpful to differentiate PD among SWEDDs
patients. PATIENTS AND METHODS: 145 patients with clinically suspected PD
underwent both DAT-SPECT and MIBG myocardial scintigraphy. Striatal binding ratio
(SBR) of DAT-SPECT and heart-to-mediastinal (H/M) ratio and washout rate (WR) of
MIBG myocardial scintigraphy were calculated. RESULTS: Among 18 SWEDDs patients
(12.4%), 11 were finally diagnosed with PD based on follow-up for at least two
years after the DAT-SPECT and MIGB myocardial scintigraphy scans. Among the
latter group, 8 patients showed an H/M ratio of less than 2.2, and 9 showed WR
above 30%. CONCLUSION: Our results indicate that the combination of low H/M ratio
and high WR of MIBG myocardial scintigraphy of SWEDDs patients may be helpful for
detection of PD patients.
PMID- 28689104
TI - #fitspo or #loveyourself? The impact of fitspiration and self-compassion
Instagram images on women's body image, self-compassion, and mood.
AB - This study experimentally examined the impact of exposure to fitspiration images
and self-compassion quotes on social media on young women's body satisfaction,
body appreciation, self-compassion, and negative mood. Female undergraduate
students (N=160) were randomly assigned to view either Instagram images of
fitspiration, self-compassion quotes, a combination of both, or appearance
neutral images. Results showed no differences between viewing fitspiration images
compared to viewing neutral images, except for poorer self-compassion among those
who viewed fitspiration images. However, women who viewed self-compassion quotes
showed greater body satisfaction, body appreciation, self-compassion, and reduced
negative mood compared to women who viewed neutral images. Further, viewing a
combination of fitspiration images and self-compassion quotes led to positive
outcomes compared to viewing only fitspiration images. Trait levels of thin-ideal
internalisation moderated some effects. The findings suggest that self-compassion
might offer a novel avenue for attenuating the negative impact of social media on
women's body satisfaction.
PMID- 28689105
TI - Structuring educational decisions using the multiple sorting task: An example
focusing on international placements in nursing.
AB - Practical examples of the steps involved in the planning and execution of the
multiple sorting task are frequently lacking in published reports. This article
demonstrates how the multiple sorting task can be used to structure conversations
with a group of health professionals planning an international placement for
nursing students. Sixteen participants were drawn from diverse professional
backgrounds, including academia, clinical practice, government policy, and
placement administrators. Participants sorted 17 statements written on cards into
categories of their choice and noted why they sorted the cards into these
particular groups. Data were analysed using multidimensional scaling and
qualitative perspectives. The analysis identified four key themes that detailed
the participants' views about international placements. These findings
demonstrate how the multiple sorting task can be used to generate information
that facilitates the examination of important facets of health care practice that
universities could cover in preparing students for international placements.
PMID- 28689106
TI - Reinstating district nursing: A UK perspective.
AB - As policy directives gather pace for service provision to be delivered in primary
care, district nursing has not been recognised as a valuable asset to facilitate
this agenda. Investment in district nursing and specialist district nursing
education has fallen. This is concurrent with an ageing district nursing
workforce, a lack of recruitment and growing caseloads, as district nursing
adapts to meet the challenges of the complexities of contemporary healthcare in
the community. The district nurse role is complex and multifaceted and includes
working collaboratively and creatively to coordinate care. Redressing the
shortages of specialist district nurse practitioners with increased numbers of
health care support workers will not replace the skill, knowledge, experience
required to meet the complex care needs of today's society. District nursing
needs to be reinstated as the valuable asset it is, through renewed investment in
the service, research development and in specialist practice education. To
prevent extinction district nurses need to be able to demonstrate and articulate
the complexities and dynamisms of the role to reinstate themselves to their
commissioners as a valuable asset for contemporary practice that can meet current
health and social care needs effectively.
PMID- 28689107
TI - Feasibility of thermophilic anaerobic processes for treating waste activated
sludge under low HRT and intermittent mixing.
AB - Thermophilic anaerobic digestion (AD) arises as an optimized solution for the
waste activated sludge (WAS) management. However, there are few feasibility
studies using low solids content typically found in the WAS, and that consider
uncommon operational conditions such as intermittent mixing and low hydraulic
retention time (HRT). In this investigation, a single-stage pilot reactor was
used to treat WAS at low HRT (13, 9, 6 and 5 days) and intermittent mixing
(withholding mixing 2 h prior feeding). Thermophilic anaerobic digestion (55
degrees C) was initiated from a mesophilic digester (35 degrees C) by the one
step startup strategy. Although instabilities on partial alkalinity (1245-3000
mgCaCO3/L), volatile fatty acids (1774-6421 mg/L acetic acid) and biogas
production (0.21-0.09 m3/m3reactor.d) were observed, methanogenesis started to
recover in 18 days. The thermophilic treatment of WAS at 13 and 9 days HRT
efficiently converted VS into biogas (22 and 21%, respectively) and achieved high
biogas yield (0.24 and 0.22 m3/kgVSfed, respectively). Intermittent mixing
improved the retention of methanogens inside the reactor and reduced the washout
effect even at low HRT (<9 days). The negative thermal balance found was
influenced by the low solids content in the WAS (2.1% TS) and by the heat losses
from the digester walls. The energy balance and economic analyses demonstrated
the feasibility of thermophilic AD of WAS in a hypothetical full-scale system,
when the heat energy could be recovered from methane in a scenario of higher
solids concentration in the substrate (>5% TS).
PMID- 28689108
TI - Multi-objective feature selection for warfarin dose prediction.
AB - With increasing the application of decision support systems in various fields,
using such systems in different aspects of medical science has been growing.
Drug's dose prediction is one of the most important issues which can be improved
using decision support systems. In this paper, a new multi-objective feature
approach has been proposed to support warfarin dose prediction decision. Warfarin
is an anticoagulant normally used in the prevention of the formation of clots.
This research was conducted on 553 patients during 2013-2015 who were candidates
for using warfarin and their INR was in the target range. Features affecting dose
was implemented and evaluated, which were clinical and genetic characteristics
extracted, and new methods of feature selection based on multi-objective
optimization methods such as the Non-dominated Sorting Genetic Algorithm-II (NSGA
II) and Multi-Objective Particle Swarm Optimization (MOPSO) along with the
evaluation of artificial neural networks were used. Multi-objective optimization
methods have more accuracy and performance compared to the classic methods of
feature selection. Furthermore, multi-objective particle swarm optimization
algorithm has higher precision than Non-dominated Sorting Genetic Algorithm-II.
With a choice of seven features Mean Square Error (MSE), root mean square error
(RMSE) and mean absolute error (MAE) were 0.011, 0.1 and 0.109 for MOPSO,
respectively.
PMID- 28689109
TI - Organophosphate pesticides and PON1 L55M in Parkinson's disease progression.
AB - BACKGROUND: Parkinson's disease (PD) has motor and non-motor features that
contribute to its phenotype and functional decline. Organophosphate (OP)
pesticides and PON1 L55M, which influences OP metabolism, have been implicated in
multiple mechanisms related to neuronal cell death and may influence PD symptom
progression. OBJECTIVE: To investigate whether ambient agricultural OP exposure
and PON1 L55M influence the rate of motor, cognitive, and mood-related symptom
progression in PD. METHODS: We followed a longitudinal cohort of 246 incident PD
patients on average over 5years (7.5years after diagnosis), repeatedly measuring
symptom progression with the Mini-Mental State Exam (MMSE), Unified Parkinson's
Disease Rating Scale (UPDRS), and Geriatric Depressive Scale (GDS). OP exposures
were generated with a geographic information system (GIS) based exposure
assessment tool. We employed repeated-measures regression to assess associations
between OP exposure and/or PON1 L55M genotype and progression. RESULTS: High OP
exposures were associated with faster progression of motor (UPDRS beta=0.24, 95%
CI=-0.01, 0.49) and cognitive scores (MMSE beta=-0.06, 95% CI=-0.11, -0.01). PON1
55MM was associated with faster progression of motor (UPDRS beta=0.28, 95%
CI=0.08, 0.48) and depressive symptoms (GDS beta=0.07; 95% CI=0.01, 0.13). We
also found the PON1 L55M variant to interact with OP exposures in influencing
MMSE cognitive scores (beta=-1.26, 95% CI=-2.43, -0.09). CONCLUSION: Our study
provides preliminary support for the involvement of OP pesticides and PON1 in PD
related motor, cognitive, or depressive symptom progression. Future studies are
needed to replicate findings and examine whether elderly populations generally
are similarly impacted by pesticides or PON1 55M genotypes.
PMID- 28689110
TI - Persistent organic pollutants in infants and toddlers: Relationship between
concentrations in matched plasma and faecal samples.
AB - Early-childhood biomonitoring of persistent organic pollutants (POPs) is
challenging due to the logistic and ethical limitations associated with blood
sampling. We investigated using faeces as a non-invasive matrix to estimate
internal exposure to POPs. The concentrations of selected POPs were measured in
matched plasma and faecal samples collected from 20 infants/toddlers (aged 13+/
4.8months), including a repeat sample time point for 13 infants (~5months apart).
We observed higher rates of POP quantification in faeces (2g dry weight) than in
plasma (0.5mL). Among the five chemicals that had quantification frequencies over
50% in both matrices, except for HCB, log concentration in faeces (Cf) and blood
(Cb) were correlated (r>0.74, P<0.05) for p.p'-dichlorodiphenyldichloroethylene
(p,p'-DDE), 2,3',4,4',5-pentachlorobiphenyl (PCB118), 2,2',3,4,4',5'
pentachlorobiphenyl (PCB138) and 2,2',4,4',5,5'-pentachlorobiphenyl (PCB153). We
determined faeces:plasma concentration ratios (Kfb), which can be used to
estimate Cb from measurements of Cf for infants/toddlers. For a given chemical,
the variation in Kfb across individuals was considerable (CV from 0.46 to 0.70).
Between 5% and 50% of this variation was attributed to short-term intra
individual variability between successive faecal samples. This variability could
be reduced by pooling faeces samples over several days. Some of the remaining
variability was attributed to longer-term intra-individual variability, which was
consistent with previously reported observations of a decrease in Kfb over the
first year of life. The strong correlations between Cf and Cb demonstrate the
promise of using faeces for biomonitoring of these compounds. Future research on
the sources of variability in Kfb could improve the precision and utility of this
technique.
PMID- 28689111
TI - Two-dimensional ytterbium oxide nanodisks based biosensor for selective detection
of urea.
AB - Herein, we demonstrate synthesis and application of two-dimensional (2D)
rectangular ytterbium oxide (Yb2O3) nanodisks via a facile hydrothermal method.
The structural, morphological, compositional, crystallinity, and phase properties
of as-synthesized nanodisks were carried out using several analytical techniques
that showed well defined 2D rectangular nanodisks/sheet like morphologies. The
average thickness and edge length of the nanosheet structures were 20 +/- 5nm and
600 +/- 50nm, respectively. To develop urea biosensor, glassy carbon electrodes
(GCE) were modified with Yb2O3 nanodisks, followed by urease immobilization and
Nafion membrane covering (GCE/Yb2O3/Urease/Nafion). The fabricated biosensor
showed sensitivity of 124.84MUAmM-1cm-2, wide linear range of 0.05-19mM,
detection limit down to ~ 2MUM, and fast response time of ~ 3s. The developed
biosensor was also used for the urea detection in water samples through spike
recovery experiments, which illustrates satisfactory recoveries. In addition, the
obtained desirable selectivity towards specific interfering species, long-term
stability, reproducibility, and repeatability further confirm the potency of as
fabricated urea biosensor.
PMID- 28689112
TI - Selection of a new Mycobacterium tuberculosis H37Rv aptamer and its application
in the construction of a SWCNT/aptamer/Au-IDE MSPQC H37Rv sensor.
AB - A rapid and accurate detection method for Mycobacterium tuberculosis (M.
tuberculosis) is essential for effectively treating tuberculosis. However,
current detection methods cannot meet these clinical requirements because the
methods are slow or of low specificity. Consequently, a new highly specific ssDNA
aptamer against M. tuberculosis reference strain H37Rv was selected by using the
whole-cell systematic evolution of ligands by exponential enrichment technique.
The selected aptamer was used to construct a fast and highly specific H37Rv
sensor. The probe was produced by immobilizing thiol-modified aptamer on an Au
interdigital electrode (Au-IDE) of a multichannel series piezoelectric quartz
crystal (MSPQC) through Au-S bonding, and then single-walled carbon nanotubes
(SWCNTs) were bonded on the aptamer by pi-pi stacking. SWCNTs were used as a
signal indicator because of their considerable difference in conductivity
compared with H37Rv. When H37Rv is present, it replaces the SWCNTs because it
binds to the aptamer much more strongly than SWCNTs do. The replacement of SWCNTs
by H37Rv resulted in a large change in the electrical properties, and this change
was detected by the MSPQC. The proposed sensor is highly selective and can
distinguish H37Rv from Mycobacterium smegmatis (M. smegmatis) and Bacillus
Calmette-Guerin vaccine (BCG). The detection time was 70min and the detection
limit was 100cfu/mL. Compared with conventional methods, this new
SWCNT/aptamer/Au-IDE MSPQC H37Rv sensor was specific, rapid, and sensitive, and
it holds great potential for the early detection of H37Rv in clinical diagnosis.
PMID- 28689113
TI - Current advances and future visions on bioelectronic immunosensing for prostate
specific antigen.
AB - Early cancer diagnosis remains the holy-grail in the battle against cancers
progression. Tainted with debates and medical challenges, current therapeutic
approaches for prostate cancer (PCa) lack early preventive measures, rapid
diagnostic capabilities, risk factors identification, and portability, i.e. the
inherent attributes offered by the label-free biosensing devices. Electronic
assisted immunosensing systems inherit the high sensitivity and specificity
properties due to the predilection of the antigen-antibody affinity.
Bioelectronic immunosensor for PCa has attracted much attentions among the
researchers due to its high-performance, easy to prepare, rapid feedback, and
possibility for miniaturization. This review explores the current advances on
bioelectronic immunosensors for the detection of PCa biomarker revealed in the
past decade. The research milestones and current trends of the immunosensors are
reported to project the future visions in order to propel their "lab-to-market"
realization.
PMID- 28689114
TI - Shape anisotropy enhanced optomagnetic measurement for prostate-specific antigen
detection via magnetic chain formation.
AB - We demonstrate a homogeneous biosensor for the detection of multivalent targets
by combination of magnetic nanoparticle (MNP) chains and a low-cost 405nm laser
based optomagnetic system. The MNP chains are assembled in a rotating magnetic
field and stabilized by multivalent target molecules. The number of chains
remaining in zero field is proportional to the target concentration, and can be
quantified by optomagnetic measurements. The shape anisotropy of the MNP chains
enhances the biosensor system in terms of providing efficient mixing, reduction
of depletion effects (via magnetic shape anisotropy), and directly increasing the
optomagnetic signal (via optical shape anisotropy). We achieve a limit of
detection (LOD) of 5.5pM (0.82ng/mL) for the detection of a model multivalent
molecule, biotinylated anti-streptavidin, in PBS. For the measurements of
prostate-specific antigen (PSA) in 50% serum using the proposed method, we
achieve an LOD of 21.6pM (0.65ng/mL) and a dynamic detection range up to 66.7nM
(2ug/mL) with a sample-to-result time of approximately 20min. The performance for
PSA detection therefore well meets the clinical requirements in terms of LOD (the
threshold PSA level in blood is 4ng/mL) and detection range (PSA levels span from
< 0.1-104ng/mL in blood), thus showing great promise for routine PSA diagnostics
and for other in-situ applications.
PMID- 28689115
TI - Liposomal honokiol induced lysosomal degradation of Hsp90 client proteins and
protective autophagy in both gefitinib-sensitive and gefitinib-resistant NSCLC
cells.
AB - Honokiol (HK), a natural chemical isolated from Mangnolia officinalis, has shown
antitumorigenic activities when used to treat a variety of tumor cell lines. The
mechanism of honokiol activity when used to treat gefitinib-sensitive and
gefitinib-resistant non-small cell lung cancer (NSCLC) requires elucidation.
Here, the presence of liposomal honokiol (LHK) induced apoptotic and antitumor
activities in four xenograft models generated using NSCLC cell lines such as
HCC827 (gefitinib-sensitive) and H1975 (gefitinib-resistant). Mechanistic studies
revealed that LHK inhibited the Akt and Erk1/2, both EGFR signaling cascades
effectors, by promoting degradation of HSP90 client proteins (HCP), including
wild-type or mutant EGFR, Akt and C-Raf. Molecular biology assays showed that LHK
induced HCP degradation through a lysosomal pathway, rather than the canonical
proteasome protein degradation pathway. As a result of misfolded protein
accumulation, LHK induced endoplasmic reticulum (ER) stress and autophagy.
Inhibition of ER stress (with 4-phenylbutyrate) or autophagy (with small
interfering RNA) reduced LHK-induced HCP degradations. Additionally, LHK induced
autophagy showed a protective role for cancer cell as inhibition of autophagy in
vitro and in vivo by autophagosome degradation inhibitors could promote the
anticancer activity of LHK. LHK has been approved by the China Food and Drug
Administration for first-in-human clinical trials in NSCLC. The current study
will guide the design of future LHK clinical trials.
PMID- 28689116
TI - "In vivo self-assembled" nanoprobes for optimizing autophagy-mediated
chemotherapy.
AB - Autophagic therapy is regarded as a promising strategy for disease treatment.
Appropriate autophagy regulations in vivo play a crucial role in translating this
new concept from benchside to bedside. So far, emerging technologies are required
to spatially and quantitatively monitor autophagic process in vivo in order to
minimize the cytotoxity concerns associated with autophagy-mediated therapy. We
successfully demonstrate the "proof-of-concept" study on autophagy-mediated
chemotherapy in mice. Here, we describe a photoacoustic (PA) nanoprobe based on
"in vivo self-assembly" idea for real-time and quantitative detection of
autophagy in mice for the first time. The purpurin-18 (P18) monomer is connected
to hydrophilic poly(amidoamine) dendrimer (4th generation) through a peptide
(GKGSFGFTG) that can be cleaved by an autophagy-specific enzyme, i.e., ATG4B,
consequently resulting in aggregation of P18 and enhanced PA signals. Based on
this aggregation-induced "turn-on" PA signals, we noninvasively determine the
ATG4B activity for monitoring autophagy of tumor in vivo. According to the
results of PA imaging, we could optimize chemotherapy efficacy through precisely
modulating autophagy, which thereby decrease systemic toxicity from
chemotherapeutics and autophagy inhibitors. We envision it will pave the way for
developing autophagy-based treatment of diseases in the future.
PMID- 28689117
TI - Development of non-pyrogenic magnetosome minerals coated with poly-l-lysine
leading to full disappearance of intracranial U87-Luc glioblastoma in 100% of
treated mice using magnetic hyperthermia.
AB - Magnetic hyperthermia was reported to increase the survival of patients with
recurrent glioblastoma by 7 months. This promising result may potentially be
further improved by using iron oxide nanoparticles, called magnetosomes, which
are synthesized by magnetotactic bacteria, extracted from these bacteria,
purified to remove most endotoxins and organic material, and then coated with
poly-l-lysine to yield a stable and non-pyrogenic nanoparticle suspension. Due to
their ferrimagnetic behavior, high crystallinity and chain arrangement, these
magnetosomes coated with poly-l-lysine (M-PLL) are characterized by a higher
heating power than their chemically synthesized counterparts currently used in
clinical trials. M-PLL-enhanced antitumor efficacy was demonstrated by
administering 500-700 MUg in iron of M-PLL to intracranial U87-Luc tumors of 1.5
mm3 and by exposing mice to 27 magnetic sessions each lasting 30 min, during
which an alternating magnetic field of 202 kHz and 27 mT was applied. Treatment
conditions were adjusted to reach a typical hyperthermia temperature of 42
degrees C during the first magnetic session. In 100% of treated mice,
bioluminescence due to living glioblastoma cells fully disappeared 68 days
following tumor cell implantation (D68). These mice were all still alive at D350.
Histological analysis of their brain tissues revealed an absence of tumor cells,
suggesting that they were fully cured. In comparison, antitumor efficacy was less
pronounced in mice treated by the administration of IONP followed by 23 magnetic
sessions, leading to full tumor bioluminescence disappearance in only 20% of the
treated mice.
PMID- 28689118
TI - Prenatal and postnatal exposure to NO2 and child attentional function at 4-5years
of age.
AB - BACKGROUND: Prenatal and postnatal exposure to air pollution has been linked to
cognitive impairment in children, but very few studies have assessed its
association with attentional function. OBJECTIVES: To evaluate the association
between prenatal and postnatal exposure to nitrogen dioxide (NO2) and attentional
function in children at 4-5years of age. METHODS: We used data from four regions
of the Spanish INMA-Environment and Childhood-Project, a population-based birth
cohort. Using land-use regression models (LUR), we estimated prenatal and
postnatal NO2 levels in all of these regions at the participants' residential
addresses. We assessed attentional function using the Kiddie-Conners Continuous
Performance Test (K-CPT). We combined the region-specific adjusted effect
estimates using random-effects meta-analysis. RESULTS: We included 1298 children
with complete data. Prenatal exposure to NO2 was associated with an impaired
standard error of the hit reaction time (HRT(SE)) (increase of 1.12ms [95% CI;
0.22 a 2.02] per 10MUg/m3 increase in prenatal NO2) and increased omission errors
(6% [95% CI; 1.01 to 1.11] per 10MUg/m3 increase in prenatal NO2). Postnatal
exposure to NO2 resulted in a similar but borderline significant increase of
omission errors (5% [95% CI; =0.99 to 1.11] per 10MUg/m3 increase in postnatal
NO2). These associations did not vary markedly between regions, and were mainly
observed in girls. Commission errors and lower detectability were associated with
prenatal and postnatal exposure to NO2 only in some regions. CONCLUSIONS: This
study indicates that higher exposure to ambient NO2, mainly during pregnancy and
to a lesser extent postnatally, is associated with impaired attentional function
in children at 4-5years of age.
PMID- 28689119
TI - Long-term net transformation and quantitative molecular mechanisms of soil
nitrogen during natural vegetation recovery of abandoned farmland on the Loess
Plateau of China.
AB - The availability of nitrogen (N) can alter vegetation species composition and
diversity in degraded ecosystems. A comprehensive understanding of the dynamic
fate of ammonium (NH4+-N) and nitrate (NO3--N) processing and the underlying
mechanisms are still lacking, particularly in arid to semi-arid degraded
ecosystems. We compared and quantified the changes in the rates of net
ammonification (Ra), nitrification (Rn) and total mineralization (Rm) and the
abundance of bacteria, archaea, and microbial genes related to N transformation
on the northern Loess Plateau of China across a 40-year chronosequence of
farmland undergoing spontaneous restoration. We found that Ra, Rn, and Rm
decreased in grassland soils (0-30-y sites) of different ages and exhibited
significant increases at the 40-y sites. The capabilities of the soil to deliver
NH4+-N and NO3--N were not a limiting factor during the growing season after
40years of vegetation recovery. Soil mineral nitrogen may be not suitable for
predicting and assessing the long-term (approximately 40years) restoration
success and progress. The abundance of functional N genes showed differences in
sensitivity to natural vegetation recovery of abandoned farmland, which likely
reflects the fact that the multi-pathways driven by N functional microbial
communities had a large influence on the dynamic fate of NH4+-N and NO3--N.
Quantitative response relationships between net N transformation rates and
microbial genes related to N transformation were established, and these
relationships confirmed that different N transformation processes were strongly
linked with certain N functional genes, and collaboratively contributed to N
transformation as vegetation recovery progressed. Specifically, Ra was controlled
by AOA-amoA, AOB-amoA, and nxrA; Rn was governed by napA, narG, nirK, nirS, and
nosZ; and Rm was controlled by nifH, apr, AOA-amoA, AOB-amoA, nirS, and nirK.
PMID- 28689120
TI - Temperature sensitivity of total soil respiration and its heterotrophic and
autotrophic components in six vegetation types of subtropical China.
AB - The temperature sensitivity of soil respiration (Q10) is a key parameter for
estimating the feedback of soil respiration to global warming. The Q10 of total
soil respiration (Rt) has been reported to have high variability at both local
and global scales, and vegetation type is one of the most important drivers.
However, little is known about how vegetation types affect the Q10 of soil
heterotrophic (Rh) and autotrophic (Ra) respirations, despite their contrasting
roles in soil carbon sequestration and ecosystem carbon cycles. In the present
study, five typical plantation forests and a naturally developed shrub and herb
land in subtropical China were selected for investigation of soil respiration.
Trenching was conducted to separate Rh and Ra in each vegetation type. The
results showed that both Rt and Rh were significantly correlated with soil
temperature in all vegetation types, whereas Ra was significantly correlated with
soil temperature in only four vegetation types. Moreover, on average, soil
temperature explained only 15.0% of the variation in Ra in the six vegetation
types. These results indicate that soil temperature may be not a primary factor
affecting Ra. Therefore, modeling of Ra based on its temperature sensitivity may
not always be valid. The Q10 of Rh was significantly affected by vegetation
types, which indicates that the response of the soil carbon pool to climate
warming may vary with vegetation type. In contrast, differences in neither the
Q10 of Rt nor that of Ra among these vegetation types were significant.
Additionally, variation in the Q10 of Rt among vegetation types was negatively
related to fine root biomass, whereas the Q10 of Rh was mostly related to total
soil nitrogen. However, the Q10 of Ra was not correlated with any of the
environmental variables monitored in this study. These results emphasize the
importance of independently studying the temperature sensitivity of Rt and its
heterotrophic and autotrophic components.
PMID- 28689121
TI - Young calcareous soil chronosequences as a model for ecological restoration on
alkaline mine tailings.
AB - Tailings are artificial soil-forming substrates that have not been created by the
natural processes of soil formation and weathering. The extreme pH environment
and corresponding low availability of some macro- and micronutrients in alkaline
tailings, coupled with hostile physical and geochemical conditions, present a
challenging environment to native biota. Some significant nutritional constraints
to ecosystem reconstruction on alkaline tailings include i) predominant or
complete absence of combined nitrogen (N) and poor soil N retention; ii) the
limited bioavailability of some micronutrients at high soil pH (e.g., Mn, Fe, Zn
and Cu); and iii) potentially toxic levels of biologically available soil
phosphorus (P) for P-sensitive plants. The short regulatory time frames (years)
for mine closure on tailings landforms are at odds with the long time required
for natural pedogenic processes to ameliorate these factors (thousands of years).
However, there are similarities between the chemical composition and nutrient
status of alkaline tailings and the poorly-developed, very young calcareous soils
of biodiverse regions such as south-western Australia. We propose that basic
knowledge of chronosequences that start with calcareous soils may provide an
informative model for understanding the pedogenic processes required to
accelerate soil formation on tailings. Development of a functional, stable root
zone is crucial to successful ecological restoration on tailings, and three major
processes should be facilitated as early as possible during processing or in the
early stages of restoration to accelerate soil development on alkaline tailings:
i) acidification of the upper tailings profile; ii) establishment of appropriate
and resilient microbial communities; and iii) the early development of
appropriate pioneer vegetation. Achieving successful ecological restoration
outcomes on tailings landforms is likely one of the greatest challenges faced by
restoration ecologists and the mining industry, and successful restoration on
alkaline tailings likely depends upon careful management of substrate chemical
conditions by targeted amendments.
PMID- 28689122
TI - Different sizes of ZnO diversely affected the cytogenesis of the sea urchin
Paracentrotus lividus.
AB - Today nanoparticles (NPs) have many applications in commercial products due to
their small size and peculiar properties that, conversely, make them potentially
toxic for humans and the environment. ZnO NPs are largely used in many personal
care products, such as sunscreens and cosmetics. In this study the cytotoxic
effects of ZnO particles with different sizes (ZnO Bulk, >100nm; ZnO NPs, 100nm
and ZnO NPs, 14nm) upon the first developmental stages of the sea urchin
Paracentrotus lividus, are evaluated. Morphological alterations are also assessed
by embryotoxicity tests. The cytogenetic analysis highlighted that ZnO NPs
interfere with cell cycle inducing a dose-dependent decrease of mitotic activity
and chromosomal aberrations at higher concentrations (30MUM). Moreover, the
larval development was affected by ZnO NPs 100nm (EC50=0.46 [0.30-0.63] MUM [Zn])
in a dose-dependent way. Size-dependent toxicity was instead not obtained for ZnO
NPs. From our results could be highlighted that the presence of embryos, blocked
in pre-larval stage, could be due to the induction of chromosome aberrations by
ZnO particles, confirming that cytogenetic analyses allow evaluating possible NPs
action mechanisms.
PMID- 28689123
TI - Pyrolysis of attapulgite clay blended with yak dung enhances pasture growth and
soil health: Characterization and initial field trials.
AB - Recent studies have shown that the pyrolysis of biomass combined with clay can
result in both lower cost and increase in plant yields. One of the major sources
of nutrients for pasture growth, as well as fuel and building materials in Tibet
is yak dung. This paper reports on the initial field testing in a pasture setting
in Tibet using yak dung, biochar, and attapulgite clay/yak dung biochars produced
at ratios of 10/90 and 50/50 clay to dung. We found that the treatment with
attapulgite clay/yak dung (50/50) biochar resulted in the highest pasture yields
and grass nutrition quality. We also measured the properties and yields of
mixtures of clay/yak dung biochar used in the field trials produced at 400
degrees C and 500 degrees C to help determine a possible optimum final pyrolysis
temperature and dung/clay ratio. It was observed that increasing clay content
increased carbon stability, overall biochar yield, pore size, carboxyl and
ketone/aldehyde functional groups, hematite and ferrous/ferric
sulphate/thiosulphate concentration, surface area and magnetic moment. Decreasing
clay content resulted in higher pH, CEC, N content and an enhanced ability to
accept and donate electrons. The resulting properties were a complex function of
both processing temperature and the percentage of clay for the biochars processed
at both 400 degrees C and 500 degrees C. It is possible that the increase in
yield and nutrient uptake in the field trial is related to the higher
concentration of C/O functional groups, higher surface area and pore volume and
higher content of Fe/O/S nanoparticles of multiple oxidation state in the 50/50
clay/dung. These properties have been found to significantly increase the
abundance of beneficial microorganisms and hence improve the nutrient cycling and
availability in soil. Further field trials are required to determine the optimum
pyrolysis production conditions and application rate on the abundance of
beneficial microorganisms, yields and nutrient quality.
PMID- 28689124
TI - Coral trace metal of natural and anthropogenic influences in the northern South
China Sea.
AB - The composition and concentrations of trace metals in coastal seawater have
changed in parallel with variations in geochemical processes, climate and
anthropogenic activities. To evaluate the response of trace metals in coastal
seawater to climatic changes and human disturbances, we report annual-resolution
trace element data for a Porites coral core covering ~100years of continuous
growth from a fringing reef in Xiaodonghai Bay in the northern South China Sea.
The results suggested that the trace metal contents in the coral skeleton
demonstrated decadal to interdecadal fluctuations with several large or small
peaks in certain years with remarkable environmental significances. All of the
trace metals in coastal surface seawater, especially Cr and Pb (related to
industrial or traffic emissions), were impacted by terrestrial inputs, except for
Sr and U, which were impacted by the surface seawater temperature (SST).
Moreover, Mn, Ni, Fe and Co were also contributed by weapons and military
supplies during wars, and Cu, Cd and Zn were further impacted by upwelling
associated with their biogeochemical cycles. Ba and rare earth element (REE) in
coastal surface seawater were dominated by runoff and groundwater discharge
associated with precipitation. This study provided the potential for some trace
metals (e.g., REE, Ba, Cu, Cd, and Zn) in coral skeletons to be used as proxies
of natural (e.g., upwelling and precipitation) and anthropogenic (e.g., war and
coastal construction) variability of seawater chemistry to enable the
reconstruction of environmental and climatic changes through time.
PMID- 28689125
TI - Removal of pharmaceuticals in pre-denitrifying MBBR - Influence of organic
substrate availability in single- and three-stage configurations.
AB - Due to the limited efficiency of conventional biological treatment, innovative
solutions are being explored to improve the removal of trace organic chemicals in
wastewater. Controlling biomass exposure to growth substrate represents an
appealing option for process optimization, as substrate availability likely
impacts microbial activity, hence organic trace chemical removal. This study
investigated the elimination of pharmaceuticals in pre-denitrifying moving bed
biofilm reactors (MBBRs), where biofilm exposure to different organic substrate
loading and composition was controlled by reactor staging. A three-stage MBBR and
a single-stage reference MBBR (with the same operating volume and filling ratio)
were operated under continuous-flow conditions (18 months). Two sets of batch
experiments (day 100 and 471) were performed to quantify and compare
pharmaceutical removal and denitrification kinetics in the different MBBRs.
Experimental results revealed the possible influence of retransformation (e.g.,
from conjugated metabolites) and enantioselectivity on the removal of selected
pharmaceuticals. In the second set of experiments, specific trends in
denitrification and biotransformation kinetics were observed, with highest and
lowest rates/rate constants in the first (S1) and the last (S3) staged sub
reactors, respectively. These observations were confirmed by removal efficiency
data obtained during continuous-flow operation, with limited removal (<10%) of
recalcitrant pharmaceuticals and highest removal in S1 within the three-stage
MBBR. Notably, biotransformation rate constants obtained for non-recalcitrant
pharmaceuticals correlated with mean specific denitrification rates, maximum
specific growth rates and observed growth yield values. Overall, these findings
suggest that: (i) the long-term exposure to tiered substrate accessibility in the
three-stage configuration shaped the denitrification and biotransformation
capacity of biofilms, with significant reduction under substrate limitation; (ii)
biotransformation of pharmaceuticals may have occurred as a result of
cometabolism by heterotrophic denitrifying bacteria.
PMID- 28689126
TI - Dynamic modeling of nutrient removal by a MBR operated at elevated temperatures.
AB - The process performance of a MBR operated on municipal sewage at elevated
temperatures was evaluated by dynamic modeling. The enhanced biological
phosphorus removal (EBPR) performance varied from 40% to 95% with process
temperature ranging from 24 to 38 degrees C. The respective maximum substrate
uptake rate (qPHA) was estimated at 1.5 gCODS/gCODX.day-1 for Glycogen
Accumulating Organisms (GAO) and 4.7 gCODS/gCODX.day-1 for Phosphate Accumulating
Organisms (PAO) with Arrhenius coefficients (theta) for GAOs and PAOs of 1.06 and
1.04 respectively. With these parameters the effluent PO4 levels of the MBR
operated for 450 days could be well described. In addition, the impact of
mesophilic conditions and low influent P/VFA levels on GAO proliferation was
evaluated under dynamic process conditions. Nitrification process was temporarily
impaired at high temperatures around 38 degrees C. Simulations revealed that the
contribution of the anoxic reactor to the total overall denitrification was
limited to 40%The contribution of simultaneous nitrification and denitrification
(SNdN) process to the denitrification was around 40-50% depending upon dissolved
oxygen levels in aerobic and MBR tanks. The large contribution of SNdN was due to
gas/liquid mass transfer limitation conditions mediated by high mixed liquor
viscosities (20-35 mPa.S) in MBR system. The membrane flux was 43 L/m2/h
corresponding to the specific permeability (K) of 413 L/m2/h/bar at 38 degrees
C.
PMID- 28689127
TI - Low nitrous oxide production through nitrifier-denitrification in intermittent
feed high-rate nitritation reactors.
AB - Nitrous oxide (N2O) production from autotrophic nitrogen conversion processes,
especially nitritation systems, can be significant, requires understanding and
calls for mitigation. In this study, the rates and pathways of N2O production
were quantified in two lab-scale sequencing batch reactors operated with
intermittent feeding and demonstrating long-term and high-rate nitritation. The
resulting reactor biomass was highly enriched in ammonia-oxidizing bacteria, and
converted ~93 +/- 14% of the oxidized ammonium to nitrite. The low DO set-point
combined with intermittent feeding was sufficient to maintain high nitritation
efficiency and high nitritation rates at 20-26 degrees C over a period of ~300
days. Even at the high nitritation efficiencies, net N2O production was low (~2%
of the oxidized ammonium). Net N2O production rates transiently increased with a
rise in pH after each feeding, suggesting a potential effect of pH on N2O
production. In situ application of 15N labeled substrates revealed nitrifier
denitrification as the dominant pathway of N2O production. Our study highlights
operational conditions that minimize N2O emission from two-stage autotrophic
nitrogen removal systems.
PMID- 28689128
TI - Incubation of premise plumbing water samples on Buffered Charcoal Yeast Extract
agar at elevated temperature and pH selects for Legionella pneumophila.
AB - Worldwide, over 90% of the notified cases of Legionnaires' disease are caused by
Legionella pneumophila. However, the standard culture medium for the detection of
Legionella in environmental water samples, Buffered Charcoal Yeast Extract (BCYE)
agar of pH 6.9 +/- 0.4 with or without antimicrobial agents incubated at 36 +/- 1
degrees C, supports the growth of a large diversity of Legionella species. BCYE
agar of elevated pH or/and incubation at elevated temperature gave strongly
reduced recoveries of most of 26 L. non-pneumophila spp. tested, but not of L.
pneumophila. BCYE agar of pH 7.3 +/- 0.1, incubated at 40 +/- 0.5 degrees C
(BCYE pH 7.3/40 degrees C) was tested for selective enumeration of L.
pneumophila. Of the L. non-pneumophila spp. tested, only L. adelaidensis and L.
londiniensis multiplied under these conditions. The colony counts on BCYE pH
7.3/40 degrees C of a L. pneumophila serogroup 1 strain cultured in tap water
did not differ significantly from those on BCYE pH 6.9/36 degrees C when
directly plated and after membrane filtration and showed repeatability's of 13
14%. By using membrane filtration L. pneumophila was detected in 58 (54%) of 107
Legionella-positive water samples from premise plumbing systems under one or both
of these culture conditions. The L. pneumophila colony counts (log-transformed)
on BCYE pH 7.3/40 degrees C were strongly related (r2 = 0.87) to those on BCYE
pH 6.9/36 degrees C, but differed significantly (p < 0.05) by a mean of - 0.12
+/- 0.30 logs. L. non-pneumophila spp. were detected only on BCYE pH 6.9/36
degrees C in 49 (46%) of the samples. Hence, BCYE pH 7.3/40 degrees C can
facilitate the enumeration of L. pneumophila and their isolation from premise
plumbing systems with culturable L. non-pneumophila spp., some of which, e.g. L.
anisa, can be present in high numbers.
PMID- 28689129
TI - The potential implications of reclaimed wastewater reuse for irrigation on the
agricultural environment: The knowns and unknowns of the fate of antibiotics and
antibiotic resistant bacteria and resistance genes - A review.
AB - The use of reclaimed wastewater (RWW) for the irrigation of crops may result in
the continuous exposure of the agricultural environment to antibiotics,
antibiotic resistant bacteria (ARB) and antibiotic resistance genes (ARGs). In
recent years, certain evidence indicate that antibiotics and resistance genes may
become disseminated in agricultural soils as a result of the amendment with
manure and biosolids and irrigation with RWW. Antibiotic residues and other
contaminants may undergo sorption/desorption and transformation processes (both
biotic and abiotic), and have the potential to affect the soil microbiota.
Antibiotics found in the soil pore water (bioavailable fraction) as a result of
RWW irrigation may be taken up by crop plants, bioaccumulate within plant tissues
and subsequently enter the food webs; potentially resulting in detrimental public
health implications. It can be also hypothesized that ARGs can spread among soil
and plant-associated bacteria, a fact that may have serious human health
implications. The majority of studies dealing with these environmental and social
challenges related with the use of RWW for irrigation were conducted under
laboratory or using, somehow, controlled conditions. This critical review
discusses the state of the art on the fate of antibiotics, ARB and ARGs in
agricultural environment where RWW is applied for irrigation. The implications
associated with the uptake of antibiotics by plants (uptake mechanisms) and the
potential risks to public health are highlighted. Additionally, knowledge gaps as
well as challenges and opportunities are addressed, with the aim of boosting
future research towards an enhanced understanding of the fate and implications of
these contaminants of emerging concern in the agricultural environment. These are
key issues in a world where the increasing water scarcity and the continuous
appeal of circular economy demand answers for a long-term safe use of RWW for
irrigation.
PMID- 28689130
TI - Metagenomic analysis reveals wastewater treatment plants as hotspots of
antibiotic resistance genes and mobile genetic elements.
AB - The intensive use of antibiotics results in their continuous release into the
environment and the subsequent widespread occurrence of antibiotic resistant
bacteria (ARB), antibiotic resistance genes (ARGs) and mobile genetic elements
(MGEs). This study used Illumina high-throughput sequencing to investigate the
broad-spectrum profiles of both ARGs and MGEs in activated sludge and
anaerobically digested sludge from a full-scale wastewater treatment plant. A
pipeline for identifying antibiotic resistance determinants was developed that
consisted of four categories: gene transfer potential, ARG potential, ARGs
pathway and ARGs phylogenetic origin. The metagenomic analysis showed that the
activated sludge and the digested sludge exhibited different microbial
communities and changes in the types and occurrence of ARGs and MGEs. In total,
42 ARGs subtypes were identified in the activated sludge, while 51 ARG subtypes
were detected in the digested sludge. Additionally, MGEs including plasmids,
transposons, integrons (intI1) and insertion sequences (e.g. ISSsp4, ISMsa21 and
ISMba16) were abundant in the two sludge samples. The co-occurrence pattern
between ARGs and microbial taxa revealed by network analysis indicated that some
environmental bacteria (e.g. Clostridium and Nitrosomonas) might be potential
hosts of multiple ARGs. The findings increase our understanding of WWTPs as
hotspots of ARGs and MGEs, and contribute towards preventing their release into
the downstream environment.
PMID- 28689131
TI - A novel fuzzy-logic control strategy minimizing N2O emissions.
AB - A novel control strategy for achieving low N2O emissions and low effluent NH4+
concentration is here proposed. The control strategy uses the measurements of
ammonium and nitrate concentrations in inlet and outlet of the aerobic zone of a
wastewater treatment plant to calculate a ratio indicating the balance among the
microbial groups. More specifically, the ratio will indicate if there is a
complete nitrification. In case nitrification is not complete, the controller
will adjust the aeration level of the plant in order to inhibit the production of
N2O from AOB and HB denitrification. The controller was implemented using the
fuzzy logic approach. It was comprehensively tested for different model
structures and different sets of model parameters with regards to its ability of
mitigating N2O emissions for future applications in real wastewater treatment
plants. It is concluded that the control strategy is useful for those plants
having AOB denitrification as the main N2O producing process. However, in
treatment plants having incomplete NH2OH oxidation as the main N2O producing
pathway, a cascade controller configuration adapting the oxygen supply to respect
only the effluent ammonium concentration limits was found to be more effective to
ensure low N2O emissions.
PMID- 28689132
TI - New insights into the spatial variability of biofilm communities and potentially
negative bacterial groups in hydraulic concrete structures.
AB - The composition and distribution characteristics of bacterial communities in
biofilms attached to hydraulic concrete structure (HCS) surfaces were
investigated for the first time in four reservoirs in the middle and lower
reaches of the Yangtze River Basin using 16S rRNA Miseq sequencing. High
microbial diversity was found in HCS biofilms, and notable differences were
observed in different types of HCS. Proteobacteria, Cyanobacteria and Chloroflexi
were the predominant phyla, with respective relative abundances of 35.3%, 25.4%
and 13.0%. The three most abundant genera were Leptolyngbya, Anaerolineaceae and
Polynucleobacter. The phyla Beta-proteobacteria and Firmicutes and genus Lyngbya
were predominant in CGP, whereas the phyla Cyanobacteria and Chloroflexi and
genera Leptolyngbya, Anaerolinea and Polynucleobacter survived better in land
walls and bank slopes. Dissolved oxygen, ammonia nitrogen and temperature were
characterized as the main factors driving the bacterial community composition.
The most abundant groups of metabolic functions were also identified as ammonia
oxidizers, sulphate reducers, and dehalogenators. Additionally, functional groups
related to biocorrosion were found to account for the largest proportion (14.0%
of total sequences) in gate piers, followed by those in land walls (11.5%) and
bank slopes (10.2%). Concrete gate piers were at the greatest risk of
biocorrosion with the most abundant negative bacterial groups, especially for
sulphate reducers. Thus, it should be paid high attention to the biocorrosion
prevention of concrete gate piers. Overall, this study contributed to the
optimization of microbial control and the improvement of the safety management
for water conservation structures.
PMID- 28689133
TI - The European politics of animal experimentation: From Victorian Britain to 'Stop
Vivisection'.
AB - This paper identifies a common political struggle behind debates on the validity
and permissibility of animal experimentation, through an analysis of two recent
European case studies: the Italian implementation of the European Directive
2010/63/EC regulating the use of animals in science, and the recent European
Citizens' Initiative (ECI) 'Stop Vivisection'. Drawing from a historical parallel
with Victorian antivivisectionism, we highlight important threads in our case
studies that mark the often neglected specificities of debates on animal
experimentation. From the representation of the sadistic scientist in the XIX
century, to his/her claimed capture by vested interests and evasion of public
scrutiny in the contemporary cases, we show that animals are not simply the focus
of the debate, but also a privileged locus at which much broader issues are being
raised about science, its authority, accountability and potential misalignment
with public interest. By highlighting this common socio-political conflict
underlying public controversies around animal experimentation, our work prompts
the exploration of modes of authority and argumentation that, in establishing the
usefulness of animals in science, avoid reenacting the traditional divide between
epistemic and political fora.
PMID- 28689134
TI - Was Mackenbach right? Towards a practical political science of redistribution and
health inequalities.
AB - In 2010, Mackenbach reflected on England's lack of success in reducing health
inequalities between 1997 and 2010, asserting that "it is difficult to imagine a
longer window of opportunity for tackling health inequalities"; asking "[i]f this
did not work, what will?"; and concluding that reducing health inequalities was
not politically feasible at least in that jurisdiction. Exploring the empirics of
that observation offers a window into the politics of reducing health
inequalities. For purposes of future comparative research, I outline three (not
mutually exclusive) perspectives on political feasibility, identify their
implications for a political science of health inequalities, and explore what
they mean for advocacy in support of reducing those inequalities.
PMID- 28689135
TI - Deformation and fatigue of tough 3D printed elastomer scaffolds processed by
fused deposition modeling and continuous liquid interface production.
AB - Polyurethane (PU) based elastomers continue to gain popularity in a variety of
biomedical applications as compliant implant materials. In parallel, advancements
in additive manufacturing continue to provide new opportunities for biomedical
applications by enabling the creation of more complex architectures for tissue
scaffolding and patient specific implants. The purpose of this study was to
examine the effects of printed architecture on the monotonic and cyclic
mechanical behavior of elastomeric PUs and to compare the structure-property
relationship across two different printing approaches. We examined the tensile
fatigue of notched specimens, 3D crosshatch scaffolds, and two 3D spherical pore
architectures in a physically crosslinked polycarbonate urethane (PCU) printed
via fused deposition modeling (FDM) as well as a photo-cured, chemically
crosslinked, elastomeric PU printed via continuous liquid interface production
(CLIP). Both elastomers were relatively tolerant of 3D geometrical features as
compared to stiffer synthetic implant materials such as PEEK and titanium. PCU
and crosslinked PU samples with 3D porous structures demonstrated a reduced
tensile failure stress as expected without a significant effect on tensile
failure strain. PCU crosshatch samples demonstrated similar performance in strain
based tensile fatigue as solid controls; however, when plotted against stress
amplitude and adjusted by porosity, it was clear that the architecture had an
impact on performance. Square shaped notches or pores in crosslinked PU appeared
to have a modest effect on strain-based tensile fatigue while circular shaped
notches and pores had little impact relative to smooth samples. When plotted
against stress amplitude, any differences in fatigue performance were small or
not statistically significant for crosslinked PU samples. Despite the slight
difference in local architecture and tolerances, crosslinked PU solid samples
were found to perform on par with PCU solid samples in tensile fatigue, when
appropriately adjusted for material hardness. Finally, tests of samples with
printed architecture localized to the gage section revealed an effect in which
fatigue performance appeared to drastically improve despite the localization of
strain.
PMID- 28689136
TI - Strain-induced phase transformation behavior of stabilized zirconia ceramics
studied via nanoindentation.
AB - To study the tetragonal-to-monoclinic (T-M) phase transformation behavior under
different strain rates and indentation depths, nanoindentation tests were
performed on stabilized zirconia ceramics with Continuous Stiffness Measurements.
The results indicate decreased phase transformation velocities at both lower and
higher strain rates, but increased velocity under medium strain rate during
loading. The phase transformation process is sensitive to P/P but the final
volume fractions are almost identical (45%). Furthermore, most of the phase
transformation is completed during a short initial time followed by slight linear
increase of the M-phase volume fraction with holding time. The phase
transformation continuously slowed with increasing indentation depth when
indented with a constant strain rate.
PMID- 28689137
TI - A simplified model for equilibrium and transient swelling of thermo-responsive
gels.
AB - A simplified model is developed for the elastic response of thermo-responsive
gels subjected to swelling under an arbitrary deformation with finite strains.
The constitutive equations involve five adjustable parameters that are determined
by fitting observations in equilibrium water uptake tests and T-jump transient
tests on thin gel disks. Two scenarios for water release under heating are
revealed by means of numerical simulation. When the final temperature in a T-jump
test is below the volume-phase transition temperature, deswelling is
characterized by smooth distribution of water molecules and small tensile
stresses. When the final temperature exceeds the critical temperature, a gel disk
is split into three regions (central part with a high concentration of water
molecules and two domains near the boundaries with low water content) separated
by sharp interfaces, whose propagation is accompanied by development of large
(comparable with the elastic modulus) tensile stresses.
PMID- 28689138
TI - Enhanced DNA double-strand break repair of microbeam targeted A549 lung carcinoma
cells by adjacent WI38 normal lung fibroblast cells via bi-directional signaling.
AB - Understanding the mechanisms underlying the radiation-induced bystander effect
(RIBE) and bi-directional signaling between irradiated carcinoma cells and their
surrounding non-irradiated normal cells is relevant to cancer radiotherapy. The
present study investigated propagation of RIBE signals between human lung
carcinoma A549 cells and normal lung fibroblast WI38 cells in bystander cells,
either directly or indirectly contacting irradiated A549 cells. We prepared A549
GFP/WI38 co-cultures and A549-GFP/A549 co-cultures, in which A549-GFP cells
stably expressing H2BGFP were co-cultured with either A549 cells or WI38 cells,
respectively. Using the SPICE-NIRS microbeam, only the A549-GFP cells were
irradiated with 500 protons per cell. The level of gamma-H2AX, a marker for DNA
double-strand breaks (DSB), was subsequently measured for up to 24h post
irradiation in three categories of cells: (1) "targeted"/irradiated A549-GFP
cells; (2) "neighboring"/non-irradiated cells directly contacting the "targeted"
cells; and (3) "distant"/non-irradiated cells, which were not in direct contact
with the "targeted" cells. We found that DSB repair in targeted A549-GFP cells
was enhanced by co-cultured WI38 cells. The bystander response in A549-GFP/A549
cell co-cultures, as marked by gamma-H2AX levels at 8h post-irradiation, showed a
decrease to non-irradiated control level when approaching 24h, while the
neighboring/distant bystander WI38 cells in A549-GFP/WI38 co-cultures was
maintained at a similar level until 24h post-irradiation. Surprisingly, distant
A549-GFP cells in A549-GFP/WI38 co-cultures showed time dependency similar to
bystander WI38 cells, but not to distant cells in A549-GFP/A549 co-cultures.
These observations indicate that gamma-H2AX was induced in WI38 cells as a result
of RIBE. WI38 cells were not only involved in rescue of targeted A549, but also
in the modification of RIBE against distant A549-GFP cells. The present results
demonstrate that radiation-induced bi-directional signaling had extended a
profound influence on cellular sensitivity to radiation as well as the
sensitivity to RIBE.
PMID- 28689139
TI - The effect of hydrophilic amines on hydrothermal liquefaction of macroalgae
residue.
AB - Hydrothermal liquefaction (HTL) of macroalgae residue was accomplished with seven
kinds of amine catalysts for chemical and bio-oil production. The effect of HTL
conditions on product distribution was investigated, and results showed that both
temperature and amines concentration have significant effects on conversion of
macroalgae residue to liquid products and bio-oil. The effect of different amines
on composition of liquid products and bio-oil was also studied. The main
ingredient of liquid products were organic acids, and the yield of organic acids
declined with the increase of alkyl chain in amines. The yield of bio-oil
increased with the addition of alkyl chain for primary amines and tertiary
amines, while decreased for secondary amines. Methylamine had the highest yield
of liquid products of 79.09wt%, and the highest bio-oil yield of 24.37wt% was
obtained in the presence of triethylamine.
PMID- 28689140
TI - Effects of dilute-acid pretreatment conditions on filtration performance of corn
stover hydrolyzate.
AB - The reaction conditions used during dilute-acid pretreatment of lignocellulosic
biomass control the carbohydrate digestion yield and also hydrolyzate properties.
Depending on the conversion route of interest, solid-liquid separation (SLS) may
be required to split the hemicellulose-rich liquor from the cellulose-rich
insoluble solids, and slurry properties are important for SLS. Corn stover was
pretreated at different reaction conditions and the slurries were assessed for
conversion yield and filtration performance. Increasing pretreatment temperature
reduced the solids mean particle size and resulted in slower slurry filtration
rates when vacuum filtered or pressure filtered. Corn stover pretreated at 165
degrees C for 10min and with 1% H2SO4 exhibited the highest xylose yield and best
filtration performance with a no-wash filtration rate of 80kg/hm2 and cake
permeability of 15x10-15.
PMID- 28689141
TI - Characteristics and kinetics study of simultaneous pyrolysis of microalgae
Chlorella vulgaris, wood and polypropylene through TGA.
AB - Thermal decomposition behavior and kinetics of microalgae Chlorella vulgaris,
wood and polypropylene were investigated using thermogravimetric analysis (TGA).
Experiments were carried out at heating rates of 10, 20 and 40 degrees C/min from
ambient temperature to 600 degrees C. The results show that pyrolysis process of
C. vulgaris and wood can be divided into three stages while pyrolysis of
polypropylene occurs almost totally in one step. It is shown that wood can delay
the pyrolysis of microalgae while microalgae can accelerate the pyrolysis of
wood. The existence of polymer during the pyrolysis of microalgae or wood will
lead to two divided groups of peaks in DTG curve of mixtures. The results showed
that interaction is inhibitive rather than synergistic during the decomposition
process of materials. Kinetics of process is studied by the Kissinger-Akahira
Sunose (KAS) and Flynn-Wall-Ozawa (FWO). The average E values obtained from FWO
and KAS methods were 131.228 and 142.678kJ/mol, respectively.
PMID- 28689142
TI - Factors associated with post-traumatic stress symptoms among adolescents exposed
to the Sewol ferry disaster in Korea.
AB - This study evaluated the factors associated with post-traumatic stress symptoms
in Korean adolescents who lived in a disaster-affected community. A total of 1101
students attending secondary and high schools in Jindo, the location of the Sewol
ferry disaster, were enrolled in a cross-sectional survey. The Child Report of
Post-traumatic Symptoms (CROPS), the Center for Epidemiological Studies
Depression Scale (CES-D), and the State Anxiety Inventory for Children (SAIC)
were administered. Female gender, older children, poor academic achievement, and
directly witnessing the rescue scene were associated with post-traumatic stress
symptoms. The CES-D and SAIC scores of subjects with witness of the rescue were
significantly higher than those of respondents without such experiences. The
regression analysis revealed that directly witnessing the rescue scene was
significantly associated with post-traumatic stress symptoms after adjusting for
other variables. The results of this study suggest that witnessing the rescue
scene following a disaster might be a risk factor for post-traumatic stress
symptoms in adolescents in disaster-affected communities.
PMID- 28689143
TI - Glial Cell Line-Derived Neurotrophic Factor (GDNF) serum level in women with
schizophrenia and depression, correlation with clinical and metabolic parameters.
AB - AIM: Neurotrophic factors have been implicated in neuropsychiatric disorders,
including schizophrenia and depression. Glial Cell Line-Derived Neurotrophic
Factor (GDNF) promotes development, differentiation, and protection of
dopaminergic, serotonergic, GABAergic and noradrenergic neurons as well as glial
cells in different brain regions. This study examined serum levels of GDNF in
schizophrenia and depression and its correlation with metabolic parameters during
8 weeks of treatment. METHODS: Serum GDNF level, fasting serum glucose and lipid
profile were measured at baseline and week 8 in 133 women: 55 with schizophrenia,
30 with a first episode depression and 48 healthy controls. The severity of the
symptoms was evaluated using Positive and Negative Syndrome Scale (PANSS), 17
item Hamilton Depression Rating Scale (HDRS) and Beck Depression Inventory (BDI).
RESULTS: There was statistically significant higher GDNF level in schizophrenia
at baseline when compared with week 8. Correlations of GDNF with PANSS in
schizophrenia and cholesterol level in depression have also been detected.
CONCLUSIONS: To our knowledge, this is the first study which correlates GDNF
levels with metabolic parameters. Our results show no differences in GDNF serum
level between schizophrenia, a first depressive episode, and healthy controls.
GDNF serum level did not correlate with metabolic parameters except for total
cholesterol in depression.
PMID- 28689144
TI - Sequence variation in the B1 gene among Toxoplasma gondii isolates from swine and
cats in Italy.
AB - The evaluation of the genetic variations of Toxoplasma gondii among isolates of a
wide variety of animal hosts can provide significant information for better
understanding the epidemiology and population structure of the parasite in
different geographical areas. The aim of this study was to provide information on
T. gondii genetic diversity in host species living in central Italy, which could
act as a potential source of human infection. Seventy-seven feline faecal
samples, and 36 and 20 diaphragm pillar tissue samples from pigs and wild boars
were collected in Umbria (central Italy). The samples were tested by a nested-PCR
protocol amplifying an informative region within the B1 gene, a multi-copy
genetic target, showing a good rate of variability. Thirty-six specimens (27.07%)
belonging to 10 pigs, 13 wild boars and 13 cats, tested positive to the B1 nested
PCR screening. Of these, 23 good quality sequences (8 from wild boars, 5 from
pigs, and 10 from cats) were analyzed. A comparison of the B1 DNA sequences
showed that a single homogeneous nucleotide substitution (C/T) was present at
position 31 in the isolates from pigs and wild boars compared with the sampled
cats and other hosts (including humans) available in GenBankTM. The present
results suggest the existence of a T. gondii genetic diversity for swine host
species, based on a SNP (C/T) of the B1 gene. Further studies are needed to draw
more solid conclusions on the discriminatory power of the B1 target by collecting
more swine samples from much broader geographical areas.
PMID- 28689145
TI - Allosteric regulation of epigenetic modifying enzymes.
AB - Epigenetic enzymes including histone modifying enzymes are key regulators of gene
expression in normal and disease processes. Many drug development strategies to
target histone modifying enzymes have focused on ligands that bind to enzyme
active sites, but allosteric pockets offer potentially attractive opportunities
for therapeutic development. Recent biochemical studies have revealed roles for
small molecule and peptide ligands binding outside of the active sites in
modulating the catalytic activities of histone modifying enzymes. Here we
highlight several examples of allosteric regulation of epigenetic enzymes and
discuss the biological significance of these findings.
PMID- 28689146
TI - Chemical modulators for epigenome reader domains as emerging epigenetic therapies
for cancer and inflammation.
AB - Site-specific lysine acetylation and methylation on histones are critical post
translational modifications (PTMs) that govern ordered gene transcription in
chromatin. Mis-regulation of these histone PTM-mediated processes has been shown
to be associated with human diseases. Since the 2010 landmark reports of small
molecules (+)-JQ1 and I-BET762 that target the acetyl-lysine 'reader' Bromodomain
and Extra Terminal domain (BET) proteins, there have been relentless efforts to
develop epigenetic therapy with small molecules to modulate molecular
interactions of epigenome reader domain proteins with PTMs. In addition to BET,
the other emerging targets include non-BET acetyl-lysine and methyl-lysine reader
domains. This review covers the key chemical modulators of the aforementioned
epigenome reader proteins.
PMID- 28689147
TI - Quantitative identification of nitrate pollution sources and uncertainty analysis
based on dual isotope approach in an agricultural watershed.
AB - Quantitative identification of nitrate (NO3--N) sources is critical to the
control of nonpoint source nitrogen pollution in an agricultural watershed.
Combined with water quality monitoring, we adopted the environmental isotope
(deltaD-H2O, delta18O-H2O, delta15N-NO3-, and delta18O-NO3-) analysis and the
Markov Chain Monte Carlo (MCMC) mixing model to determine the proportions of
riverine NO3--N inputs from four potential NO3--N sources, namely, atmospheric
deposition (AD), chemical nitrogen fertilizer (NF), soil nitrogen (SN), and
manure and sewage (M&S), in the ChangLe River watershed of eastern China. Results
showed that NO3--N was the main form of nitrogen in this watershed, accounting
for approximately 74% of the total nitrogen concentration. A strong hydraulic
interaction existed between the surface and groundwater for NO3--N pollution. The
variations of the isotopic composition in NO3--N suggested that microbial
nitrification was the dominant nitrogen transformation process in surface water,
whereas significant denitrification was observed in groundwater. MCMC mixing
model outputs revealed that M&S was the predominant contributor to riverine NO3-
N pollution (contributing 41.8% on average), followed by SN (34.0%), NF (21.9%),
and AD (2.3%) sources. Finally, we constructed an uncertainty index, UI90, to
quantitatively characterize the uncertainties inherent in NO3--N source
apportionment and discussed the reasons behind the uncertainties.
PMID- 28689148
TI - Contribution of biogenic and photochemical sources to ambient VOCs during winter
to summer transition at a semi-arid urban site in India.
AB - This paper presents the sources and characteristics of ambient volatile organic
compounds (VOCs) measured using PTR-TOF-MS instrument in a metropolitan city of
India during winter to summer transition period. Mixing ratios of VOCs exhibited
strong diurnal, day-to-day and episodic variations. Methanol was the most
dominant species with monthly mean values of 18-22 pbbv. The emission ratios of
VOCs relative to benzene calculated from nighttime data were used to estimate the
relative contributions of vehicle exhaust and other sources. The increasing
daytime ratios of oxygenated-VOCs (OVOCs)/benzene and isoprene/benzene from
February to March indicates increasing contribution of photo-oxidation and
biogenic sources. Daytime fractions of acetone (18%), acetaldehyde (15%) and
isoprene (4.5%) to the sum of measured VOCs in March were higher than those in
February. Variations of VOCs at lower temperatures (<25 degrees C) were
predominantly controlled by anthropogenic sources. At high temperatures,
particularly in the range of 32-40 degrees C during March, levels of OVOCs and
isoprene were influenced by biogenic emissions. The emissions of OVOCs from
vehicle exhaust were estimated to be smaller (20-40%) than those from other
sources. The contributions of biogenic and secondary sources to OVOCs and
isoprene increased by 10-15% from winter to summer. This study provides evidence
that the winter-to-summer transition has an impact on sources and composition of
VOCs in tropical urban areas.
PMID- 28689149
TI - The response of soil and stream chemistry to decreases in acid deposition in the
Catskill Mountains, New York, USA.
AB - The Catskill Mountains have been adversely impacted by decades of acid
deposition, however, since the early 1990s, levels have decreased sharply as a
result of decreases in emissions of sulfur dioxide and nitrogen oxides. This
study examines trends in acid deposition, stream-water chemistry, and soil
chemistry in the southeastern Catskill Mountains. We measured significant
reductions in acid deposition and improvement in stream-water quality in 5
streams included in this study from 1992 to 2014. The largest, most significant
trends were for sulfate (SO42-) concentrations (mean trend of -2.5 MUeq L-1 yr
1); hydrogen ion (H+) and inorganic monomeric aluminum (Alim) also decreased
significantly (mean trends of -0.3 MUeq L-1 yr-1 for H+ and -0.1 MUeq L-1 yr-1
for Alim for the 3 most acidic sites). Acid neutralizing capacity (ANC) increased
by a mean of 0.65 MUeq L-1 yr-1 for all 5 sites, which was 4 fold less than the
decrease in SO42- concentrations. These upward trends in ANC were limited by
coincident decreases in base cations (-1.3 MUeq L-1 yr-1 for calcium +
magnesium). No significant trends were detected in stream-water nitrate (NO3-)
concentrations despite significant decreasing trends in NO3- wet deposition. We
measured no recovery in soil chemistry which we attributed to an initially low
soil buffering capacity that has been further depleted by decades of acid
deposition. Tightly coupled decreasing trends in stream-water silicon (Si) (-0.2
MUeq L-1 yr-1) and base cations suggest a decrease in the soil mineral weathering
rate. We hypothesize that a decrease in the ionic strength of soil water and
shallow groundwater may be the principal driver of this apparent decrease in the
weathering rate. A decreasing weathering rate would help to explain the slow
recovery of stream pH and ANC as well as that of soil base cations.
PMID- 28689150
TI - Association of urinary phenolic compounds, inflammatory bowel disease and chronic
diarrheal symptoms: Evidence from the National Health and Nutrition Examination
Survey.
AB - Endocrine disruptors such as phenolic compounds and parabens may be involved in
chronic non-infective disease. While products incorporating these compounds are
extensively utilized in consumer and personal products, little is known about
their effect on bowel health. Inflammatory bowel disease (IBD) - consisting of
the diseases ulcerative colitis and Crohn's disease - and irritable bowel
syndrome are common chronic non-infectious diarrheal diseases. Despite limited
knowledge on the etiology of IBD, these diseases have increased prevalence in
industrialized countries and cause significant impairment to quality of life. In
the present study we examine relationships between urinary environmental phenolic
compounds, chronic diarrhea and inflammatory bowel disease. Data was obtained
from the 2005-2010 US National Health and Nutrition Examination Survey (NHANES)
including demographics, lifestyle factors, self-reported health conditions,
inflammatory markers and urinary phenolic chemical concentrations. Only
participants with complete environmental phenols & parabens component were
included in our analysis. Chronic diarrheal symptoms were determined by using the
2009-2010 NHANES questionnaire which included questions pertaining to bowel
health. We utilized chronic bowel leakage symptoms as a surrogate marker for
chronic diarrhea. The presence of IBD was also analyzed from 2009 to 2010 NHANES
data, as a sub-analysis for arthropathy directly querying the presence or absence
of IBD. Among the subset of 5218 American adults aged 20-80 years in the NHANES
study period who completed environmental phenols & parabens component, 25.5%
reported chronic diarrheal symptoms. Abnormal markers of inflammation were
present in 2200 (42.2%) of respondents. For IBD, 19 individuals with arthropathy
confirmed a diagnosis of ulcerative colitis, and 1 person confirmed a Crohn's
diagnosis. After adjustment for demographics, inflammatory and subsample
weighing; lower paraben levels were associated with chronic bowel leakage
(diarrheal) symptoms. Higher 4-tert-octylphenol levels was significantly
associated with ulcerative colitis. Further study of underlying mechanisms should
be considered.
PMID- 28689151
TI - Remobilization of polycyclic aromatic hydrocarbons and organic matter in seawater
during sediment resuspension experiments from a polluted coastal environment:
Insights from Toulon Bay (France).
AB - Polycyclic aromatic hydrocarbons (PAHs) and organic matter contents were measured
in seawater during resuspension experiments using sediments collected from Toulon
Bay (Northwestern Mediterranean Sea, France). The studied sediments were very
highly contaminated in PAHs, especially in 4-ring compounds emitted from
combustion processes. The sediments used for resuspension experiments were
collected at 0-2 cm (diagenetically new organic matter, OM) and 30-32 cm depths
(diagenetically transformed OM). They were both mostly composed of fine particles
(<63 MUm), enriched in organic carbon (8.2 and 6.3%, respectively) and in PAHs
(concentration of Sigma34 PAHs: 38.2 and 35.7 * 103 ng g-1, respectively). The
resuspension of these sediments led to an increase in concentrations of dissolved
Sigma34 PAHs, dissolved organic carbon (DOC) and dissolved humic- and tryptophan
like fluorophores in seawater up to 10-, 1.3-, 4.4- and 5.7-fold, respectively.
The remobilization in seawater was higher for 4-6 ring PAHs, especially
benzo(g,h,i)perylene, whose concentration exceeded the threshold values of the
European Water Framework Directive. This noted the potential harmful effects of
sediment resuspension on marine biota. From these sediment resuspension
experiments, we determined OC-normalized partition coefficients of PAHs between
sediment and water (Koc) and found that during such events, the transfer of PAHs
from sediment particles to seawater was lower than that predicted from octanol
water partition coefficients (Kow) (i.e., measured Koc > Koc predicted from Kow).
The results confirmed the sequestration role of sedimentary OC quality and grain
size on PAHs; the OM diagenetic state seemed to impact the partition process but
in a relatively minor way. Furthermore, differences were observed between 2-4
ring and 5-6 ring PAHs, with the latter displaying a relatively higher mobility
towards seawater. These differences may be explained by the distribution of these
two PAH pools within different OM moieties, such as humic substances and black
carbon.
PMID- 28689152
TI - Influence of land use configurations on river sediment pollution.
AB - Land use is an influential factor in river sediment pollution. However, land use
type alone is found to be inadequate to explain pollutant contributions to the
aquatic environment since configurations within the same land use type such as
land cover and development layout could also exert an important influence.
Consequently, this paper discusses a research study, which consisted of an in
depth investigation into the relationship between land use type and river
sediment pollution by introducing robust parameters that represent configurations
within the primary land use types. Urban water pollutants, namely, nutrients,
total carbon, polycyclic aromatic hydrocarbons and metals were investigated in
the study. The outcomes show that higher patch density and more diverse land use
development forms contribute relatively greater pollutant loads to receiving
waters and consequently leading to higher sediment pollution. The study outcomes
are expected to contribute essential knowledge for creating robust management
strategies to minimise waterway pollution and thereby protect the health of
aquatic ecosystems.
PMID- 28689153
TI - Do Si/As ratios in growth medium affect arsenic uptake, arsenite efflux and
translocation of arsenite in rice (Oryza sativa)?
AB - Silicon (Si) may decrease the uptake and accumulation of arsenic (As) in rice.
However, the effects of Si/As ratios in growth medium on arsenic uptake, arsenite
efflux to the external medium and translocation of arsenite in rice are currently
unclear. Rice seedlings (Oryza sativa L.) were exposed to nutrient solutions with
10 MUM arsenite [As(III)] or 10 MUM arsenate [As(V)] to explore the influence of
different silicic acid concentrations (0, 10, 100, 1000 MUM) on arsenic uptake
and translocation of arsenite with or without 91 MUM phosphate for 24 h. Arsenic
speciation was determined in nutrient solutions, roots, and shoots. In the
arsenite treatments, different Si/As ratios (1:1, 10:1, 100:1) did not affect
As(III) uptake by rice roots, however they did inhibit translocation of As(III)
from roots to shoots significantly (P < 0.001) in the absence of P. In the
arsenate treatments, a Si/As ratio of 100:1 significantly decreased As(V) uptake
and As(III) efflux compared with the control (Si/As at 0:1), accounting for
decreases of 27.4% and 15.1% for -P treatment and 47.8% and 61.1% for + P
treatment, respectively. As(III) is the predominant species of arsenic in rice
roots and shoots. A Si/As ratio of 100:1 reduced As(III) translocation from roots
to shoots markedly without phosphate. When phosphate was supplied, As(III)
translocation from roots to shoots was significantly inhibited by Si/As ratios of
10:1 and 100:1. The results indicated that in the presence of P, different
silicic acid concentrations did not impact arsenite uptake and transport in rice
when arsenite was supplied. However, a Si/As ratio of 100:1 inhibited As(V)
uptake, as well as As(III) efflux and translocation from roots to shoots when
arsenate was supplied.
PMID- 28689154
TI - If a picture is worth a thousand words, take a good look at the picture: Survival
after liver metastasectomy for colorectal cancer.
AB - INTRODUCTION: An analysis of NHS data published in by Morris et al. in 2010 is
widely used as evidence in support of liver metastasectomy for colorectal cancer
and its wider application. Recent evidence concerning better overall survival for
patients with metastatic colorectal cancer challenges the notional assumptions
about what survival would be without metastasectomy. Earlier detection of
metastases for local treatments has not resulted in a survival benefit. MATERIALS
AND METHODS: The interpretation of its central graphical display is critically
reviewed and the common the limitations of the analysis of registry data and
resulting immortal time bias are explored. RESULTS AND DISCUSSION: Recent
evidence, including the 2017 CLOCC trial report make the original interpretation
of the analysis suspect. Randomised trials are essential to detect a treatment
effect of specific interventions among variable disease progression, selection
bias, and multiple and repeated treatments that are inherent in the management of
advanced cancer.
PMID- 28689155
TI - Combination of hemostatic therapies for treatment of patients with hemophilia A
and inhibitors.
AB - BACKGROUND: Therapy application and monitoring of patients with hemophilia A (HA)
and inhibitors are challenging. In the current study, combined FVIII - bypass
therapy was implemented for a cohort of severe HA patients with inhibitors.
METHODS: Plasma of 15 HA patients with inhibitors was spiked ex vivo with FVIII,
rFVIIa, FEIBA and their combinations and thrombin generation (TG) was studied.
Some patients who experienced hemarthroses or required minor surgeries were
treated by a combined concomitant administration of FVIII+FEIBA as IV bolus
doses. RESULTS: TG spiking studies showed individual responses not correlated to
inhibitor titer. Combinations of agents augmented TG as compared to any single
agent, while combined FVIII+FEIBA yielded the highest TG, supporting it as a
potential treatment. Following emergent successful surgery of child treated by
concomitant FVIII+FEIBA, a total of 396 episodes in 7/15 patients were treated
with concomitant FVIII+FEIBA. Five patients were treated for bleeding episodes
only, whereas 2 were children undergoing immune tolerance induction (ITI) with
FEIBA prophylaxis. Four minor surgeries were performed on FVIII+FEIBA repeated
infusions. Neither thrombosis nor any other adverse events were documented.
CONCLUSION: A combination of FVIII+FEIBA may be effective and safe as an
alternative treatment option for some high-responding inhibitor patients.
PMID- 28689156
TI - First-void urine: A potential biomarker source for triage of high-risk human
papillomavirus infected women.
AB - Great interest has been directed towards the use of first-void urine as a liquid
biopsy for high-risk human papillomavirus DNA testing. Despite the high
correlations established between urinary and cervical infections, human
papillomavirus testing is unable to distinguish between productive and
transforming high-risk infections that have the tendency to progress to cervical
cancer. Thus far, investigations have been primarily confined to the
identification of biomarkers for triage of high-risk human papillomavirus
positive women in cervicovaginal specimens and tissue biopsies. This paper
reviews urinary biomarkers for cervical cancer and triage of high-risk human
papillomavirus infections and elaborates on the opportunities and challenges that
have emerged regarding the use of first-void urine as a liquid biopsy for the
analysis of both morphological- (conventional cytology and novel
immunohistochemical techniques) and molecular-based (HPV16/18 genotyping,
host/viral gene methylation, RNA, and proteins) biomarkers. A literature search
was performed in PubMed and Web of Science for studies investigating the use of
urine as a biomarker source for cervical cancer screening. Five studies were
identified reporting on biomarkers that are still in preclinical exploratory or
clinical assay development phases and on assessments of non-invasive (urine)
samples. Although large-scale validation studies are still needed, we conclude
that methylation of both host and viral genes in urine has been proven feasible
for use as a molecular cervical cancer triage and screening biomarker in phase
two studies. This is especially promising and underscores our hypothesis that
human papillomavirus DNA and candidate human and viral biomarkers are washed away
with the initial, first-void urine, together with exfoliated cells, debris and
impurities that line the urethra opening. Similar to the limitations of self
collected cervicovaginal samples, first-void urine will likely not fulfil the
high-quality cellularity standards required for morphological biomarkers.
Molecular biomarkers will likely overcome this issue to yield high-throughput,
objective, and reproducible results. When using proper sampling, transport,
storage, preanalytical biomarker concentration techniques, and clinically
validated assays, first-void urine is expected to be a valuable source of
molecular biomarkers for cervical cancer screening. Furthermore, as first-void
urine can be easily and non-invasively collected, it is a highly preferred
technique among women and offers the ability to test both primary high-risk human
papillomavirus and biomarkers in the same sample. In addition, the use of first
void urine confers opportunities to reduce loss-to follow-up and non-adherence to
screening subjects.
PMID- 28689157
TI - Radiosynthesis of [18F]AV1451 in pharmaceutical conditions and its biological
characteristics.
AB - In this study, we describe the radiosynthesis of [18F]AV1451 in terms of its
pharmaceutical quality and characterise its physical and biological properties.
We performed an in vitro serum stability study in fresh human plasma and a plasma
protein binding study. The radiochemical yield was 24% (decay corrected), and the
product met all regulatory quality requirements. We found that this compound is
stable in fresh human plasma and binds tightly to plasma proteins, especially
lipoproteins.
PMID- 28689158
TI - Validation of zirconium isotopes (n,g) and (n,2n) cross sections in a
comprehensive LR-0 reactor operative parameters set.
AB - Zirconium is an important material used in most of reactor concepts for fuel
cladding. Thus the knowledge of its cross section is important for reliable
prediction of fuel operation. Also 90Zr(n,2n) reaction, is included in IRDFF
files as dosimetry cross section standard. Due to its very high threshold,
12.1MeV, it is suitable for measurement of high energy neutrons. One of possible
interesting applications is also evaluation of prompt fission neutron spectra in
235U and 238U what is under auspices of the International Atomic Energy Agency in
CIELO project. The experimental values - obtained with the LR-0 nuclear reactor -
of various zirconium cross sections were compared with calculations with the
MCNP6 code using IAEA CIELO, ENDF/B-VII.0, JEFF-3.1, JEFF-3.2, JENDL-3.3, JENDL
4, ROSFOND- 2010, and CENDL-3.1 transport libraries combined with the dosimetry
cross sections extracted from the IRDFF library. Generally, the best C/E
agreement for 90Zr(n,2n) cross section, was found with the IAEA CIELO 235U
evaluation that includes an updated prompt fission neutron spectra in the
evaluated data file. The cross section of this reaction averaged over LR-0
spectra was determined being 28.9 +/- 1.2 ub, corrected to spectral shift,
spectral averaged cross section in 235U was determined to be 0.107 +/- 0.005mb.
Notable discrepancies were reported in both 94Zr(n,g) and 96Zr(n,g).
PMID- 28689159
TI - Self-management support by final year nursing students: A correlational study of
performance and person-related associated factors.
AB - BACKGROUND: Chronic conditions put a heavy burden on healthcare in every country.
Supporting persons with a chronic illness to take an active role in the
management of their condition is a core component in the Chronic Care Model. It
implies confidence and good skills from professionals. To date, there is no
evidence on final year nursing students' performance in supporting patients' self
management, nor on factors associated with this performance. OBJECTIVES: To
explore self-reported performance of supporting patients' self-management by
final year nursing students, and person-related factors associated with this
performance. DESIGN: A correlational multi-centre study of final year nursing
students (N=256) from eight nursing schools. METHODS: Students were recruited
from a convenience sample of eight nursing schools. All final year students were
invited to participate. Data were collected between January 2015 and May 2016
using self-administered validated questionnaires. Theoretical behavioural
frameworks were used to select hypothesized associated factors for self
management support: self-efficacy to perform self-management support and socio
structural factors (Social Cognitive Theory); needs for autonomy, competence and
relatedness, and patient-invested contingent self-esteem (Self-Determination
Theory); and attitudes towards supporting patients' self-management (Theory of
Planned Behaviour). RESULTS: Final year nursing students (N=256) reported an
overall low level of performance in delivering self-management support during
internship. Students lacked mainly competencies in collaborative goal setting and
shared decision making. Students reported a significant gap between their
confidence and their actual performance in self-management support (p<0.001).
About 33% of the variance in students' performance is predicted by four person
related factors, i.e. self-efficacy to perform self-management support, general
feeling of competency on internship, belief on patients' knowledge about
condition management, and contingency of a student's professional self-esteem
upon patients' achievements. CONCLUSION: Final year nursing students are actually
not ready to support patients' self-management even though they will soon be in
practice as qualified nurses. Nursing curricula should be further attuned to the
complex competencies of self-management support. Special attention is needed to
broaden the perspective on self-management support. Learning opportunities can be
introduced in classroom activities and on internship.
PMID- 28689160
TI - Effects of self-management on chronic kidney disease: A meta-analysis.
AB - BACKGROUND: Self-management programs may facilitate the improvement of outcomes
in medical, role, and emotional management and health-related quality of life in
patients with chronic kidney disease. Studies on the effect of three self
management tasks have reported conflicting findings. In addition, systematic
reviews are unavailable. OBJECTIVE: This study evaluated the effects of self
management programs on medical, role, and emotional management and health-related
quality of life in chronic kidney disease. DESIGN: Meta-analysis of randomized
controlled studies. DATA SOURCES: The meta-analysis involved an online search of
the English literature from PubMed, Cochrane, Web of Science, and CINAHL and the
Chinese literature from the Airiti Library that were published from the inception
of the websites until January 1, 2017. REVIEW METHODS: The meta-analysis was
conducted to evaluate the effects of self-management on chronic kidney disease
outcomes. Electronic databases were searched by using keywords: chronic kidney
disease, end-stage renal disease, renal failure, dialysis, self-management, self
efficacy, empowerment, cognitive behavioral, and educational. The methodological
quality of randomized controlled trials was assessed using the Cochrane Handbook.
Data were analyzed using Comprehensive Meta-Analysis software 2.0. RESULTS:
Eighteen randomized controlled trials met our inclusion criteria. The results
revealed that the self-management program significantly enhanced the effects of
self-management on outcomes of medical, role, and emotional management and health
related quality of life in patients with chronic kidney disease. The following
Hedges' g (effect size) values were obtained: (1) interdialytic weight gain,
0.36 (95% confidence interval, -0.60 to -0.12, p<0.01); (2) self-efficacy, 0.57
(95% confidence interval, 0.18-0.96, p<0.01); (3) anxiety, -0.95 (95% confidence
interval, -1.65 to -0.25, p=0.01); (4) depression, -0.63 (95% confidence
interval, -0.85 to -0.41, p<0.01) (5) health-related quality of life for the
mental component of the SF-36, 0.71 (95% confidence interval, 0.45-0.97, p<0.01);
(6) the physical component of the SF-36, 0.61 (95% confidence interval, 0.35
0.86, p<0.01); and (7) the Kidney Disease Quality of Life, 0.41 (95% confidence
interval, 0.17-0.65, p<0.01). DISCUSSION: This study revealed a small effect of
self-management on interdialytic weight gain; medium effects on self-efficacy,
depression, and health-related quality of life; and a large effect on anxiety.
However, high-quality randomized controlled trial designs are required to confirm
these results, although the existing evidence can guide clinical practitioners
and health policy makers.
PMID- 28689161
TI - Atmospheric tritium concentrations under influence of AREVA NC La Hague
reprocessing plant (France) and background levels.
AB - In-air tritium measurements were conducted around the AREVA NC La Hague
reprocessing plant, as well as on other sites that are not impacted by the
nuclear industry in northwest of France. The results indicate that the dominant
tritium form around the AREVA site is HT (86%). HT and HTO levels are lower than
5 and 1 Bq. m-3 for hourly samples taken in the plume. No tritiated organic
molecules (TOM) were detected. 26 measurement campaigns were performed and links
were established between near-field 85Kr, HT and HTO activities. Environmental
measurements are in line with those taken at the discharge stack, and tend to
demonstrate that there are no rapid changes in the tritium forms released. Out of
the influence of any nuclear activities, the levels measured were below 13 mBq.m
3 for HT and 5 mBq.m-3 for HTO (<0.5 Bq. L-1). HTO level in air seems to be
influenced by HTO activities in surrounding seawater.
PMID- 28689162
TI - Imaging phospholipid conformational disorder and packing in giant multilamellar
liposome by confocal Raman microspectroscopy.
AB - Liposomes are closed phospholipid bilayer systems that have profound applications
in fundamental cell biology, pharmaceutics and medicine. Depending on the
composition (pure or mixture of phospholipids, presence of cholesterol) and
preparation protocol, intra- and inter-chain molecular interactions vary leading
to changes in the quality (order and packing) of liposomes. So far it is not
possible to image conformational disorders and packing densities within a
liposome in a straightforward manner. In this study, we utilized confocal Raman
microspectroscopy to visualize structural disorders and packing efficiency within
a giant multilamellar liposome model by focusing mainly on three regions in the
vibrational spectrum (CC stretching, CH deformation and CH stretching). We
estimated properties such as trans/gauche isomers and lateral packing
probability. Interestingly, our Raman imaging studies revealed gel phase rich
domains and heterogeneous lateral packing within the giant multilamellar
liposome.
PMID- 28689163
TI - Photophysical behavior of a potential drug candidate, trans-[2-(4
methoxystyryl)]quinoline-1-oxide tuned by environment effects.
AB - Styryl and/or quinoline structural fragments, present in a large number of
bioactive substances, inspired the design of various new drug candidates. In this
paper, we describe the photophysical behavior of trans-[2-(4
methoxystyryl)]quinoline-1-oxide (trans-MSQNO) on the basis of X-ray analysis
data, theoretical calculations as well as steady state and time-resolved
spectroscopy experiments in various media. The molecule crystallizes in
orthorhombic unit cell containing eight molecules of N-oxide, space group Pbca.
The NO bond is substantially shorter in comparison with the NO bond in the ZnTPP
unit [1.3052(11) A vs. 1.335(2) A]. Variation of emission colors from the violet
(~450nm) through blue (480nm), green (525nm) and yellow (575nm) is observed in
different environments. Comparable values of lifetimes estimated both at ambient
temperature and at 77K suggest that excited state dynamics in this case is
viscosity independent. DFT and TD DFT B3LYP/6-31G(d, p) calculations performed
for four different trans-MSQNO rotamers in the gas phase, as well as nonpolar and
polar media (PCM model) suggest that an equilibrium between them can be
significantly altered even by a relatively weak interactions with the
environment. It is suggested that varying intensity ratios of experimental
absorption bands in different media may be due to the dominant share of one or
more rotamers of the excited trans-MSQNO molecule. Gas phase calculations show
also that the vertical pipi*, S0->S1, transition resulting from the HOMO->LUMO
electronic configuration exhibits only a partial CT nature. On the other hand, in
polar media, a substantial increment of excited state dipole moment of all
rotamers compared to the ground state, its increase with increasing solvent
polarity and a significant red shift in the absorption and emission spectra,
point to the enhanced CT nature of the S1 excited state. Hence, the trans-MSQNO
molecule may be considered a subsequent styrylquinoline drug candidate where the
CT drug-receptor interactions are of a high importance.
PMID- 28689164
TI - Head impact velocities in FIS World Cup snowboarders and freestyle skiers: Do
real-life impacts exceed helmet testing standards?
AB - INTRODUCTION: Prior to the 2013-2014 season, the International Ski Federation
(FIS) increased the helmet testing speed from a minimum requirement of 5.4 to 6.8
m/s for alpine downhill, super-G and giant slalom and for freestyle ski cross,
but not for the other freestyle disciplines or snowboarding. Whether this
increased testing speed reflects impact velocities in real head injury situations
on snow is unclear. We therefore investigated the injury mechanisms and gross
head impact biomechanics in four real head injury situations among World Cup (WC)
snowboard and freestyle athletes and compared these with helmet homologation
laboratory test requirements. The helmets in the four cases complied with at
least European Standards (EN) 1077 (Class B) or American Society for Testing and
Materials (ASTM) F2040. METHODS: We analysed four head injury videos from the FIS
Injury Surveillance System throughout eight WC seasons (2006-2014) in detail. We
used motion analysis software to digitize the helmet's trajectory and estimated
the head's kinematics in two dimensions, including directly preimpact and
postimpact. RESULTS: All four impacts were to the occiput. In the four cases, the
normal-to-slope preimpact velocity ranged from 7.0(+/-SD 0.2) m/s to 10.5+/-0.5
m/s and the normal-to-slope velocity change ranged from 8.4+/-0.6 m/s to 11.7+/
0.7 m/s. The sagittal plane helmet angular velocity estimates indicated a large
change in angular velocity (25.0+/-2.9 rad/s to 49.1+/-0.3 rad/s). CONCLUSION:
The estimated normal-to-slope preimpact velocity was higher than the current
strictest helmet testing rule of 6.8 m/s in all four cases.
PMID- 28689165
TI - Tear film and ocular surface assessment in psoriasis.
AB - BACKGROUND: Psoriasis is a skin disease with also systemic involvement: its
impact on the eye is not well established and often clinically underestimated.
Aim of this study was to investigate the presence of ocular discomfort symptoms
and of ocular surface changes in a population of patients with psoriasis.
METHODS: For this cross-sectional, comparative study, 66 patients with psoriasis
were subdivided according to the presence of arthritis and to the use of
biological therapy. All patients underwent clinical evaluation with the following
tests: Ocular Surface Disease Index Questionnaire, Tearscope examination,
meibometry, tear film breakup time, corneal and conjunctival fluorescein
staining, Schirmer I test, corneal aesthesiometry, meibomian gland dysfunction
(MGD) assessment and conjunctival impression cytology. 28 healthy subjects were
also enrolled and treated with the same clinical tests. A statistical analysis of
the results was performed. RESULTS: Patients with psoriasis showed a significant
deterioration of the ocular surface tests, if compared with healthy subjects,
demonstrated by tear film lipid layer alteration, tear film instability, corneal
and conjunctival epithelial suffering and mild squamous metaplasia at impression
cytology. No differences were found in ocular surface test results of the
psoriatic group when patients were divided according to the presence of
arthritis, whereas the anti-inflammatory treatment with biological drugs
demonstrated a significant improvement of corneal stain and MGD. CONCLUSIONS: Our
findings suggest that the ocular surface involvement in patients with psoriasis
indicates the need of periodic ophthalmological examinations to diagnose the
condition and allow a proper treatment, so contributing to the amelioration of
patients' quality of life.
PMID- 28689166
TI - Ocular surface cytokine profile in chronic Stevens-Johnson syndrome and its
response to mucous membrane grafting for lid margin keratinisation.
AB - BACKGROUND: To study the tear cytokine and the conjunctival and oral mucosal
marker profile in chronic ocular Stevens-Johnson syndrome (SJS) and their
alteration following mucous membrane grafting (MMG) for lid margin keratinisation
(LMK). METHODS: In a 1-year prospective study, SJS cases (n=25) and age
matched/sex-matched healthy controls (n=25) were recruited. Tear specimen
(Schirmer's strip), conjunctival and oral mucosal imprints were collected from
controls and SJS cases pre-MMG and post-MMG (at first follow-up, n=17). Tear
cytokines were profiled using 27-bioplex array. Transforming growth factor-beta
(TGF-beta)-mediated extracellular matrix changes in conjunctival and oral mucosal
cells were analysed by gene expression studies. 30 RESULTS: Tear cytokine
profiling of chronic SJS cases at pre-MMG stage revealed significant upregulation
of cytokines granulocyte-macrophage colony-stimulating factor (GM-CSF),
interleukin (IL)-8, IL-1beta, monocyte chemoattractant protein-1, IL-15, IL-2, IL
17A and basic fibroblast growth factor (bFGF) with downregulation of IP-10
(interferon gamma-induced protein 10), tumour necrosis factor-alpha, interferon
gamma, IL-10, vascular endothelial growth factor, regulated upon activation
normal T-cell expressed and secreted (RANTES), IL-7, IL-12p70 and IL-13, with
maximal increase in GM-CSF and maximal downregulation of IP-10, respectively. Of
these, IL-2, IL-15, bFGF and IL-17A showed significant correlation with disease
severity, pre-MMG. Conjunctival cells pre-MMG showed increase in TGF-beta1, TGF
betaRII, connective tissue growth factor and collagen-III gene expression by 10,
67, 173 and 184 folds, respectively, which dropped to 1.3, 11, 13.5 and 19 folds
correspondingly, post-MMG. However, their expressions in oral mucosa were
negligible. CONCLUSION: A proinflammatory, profibrotic, antiapoptotic ocular
surface milieu characterises chronic ocular SJS. IP-10, an antifibrotic cytokine
was noted to be maximally downregulated, unlike in other forms of chronic dry eye
disease. The alterations in the ocular surface are seen to reverse largely with
MMG for LMK.
PMID- 28689167
TI - The interpretation of results of 10-2 visual fields should consider individual
variability in the position of the optic disc and temporal raphe.
AB - AIMS: To clarify the anatomical relation between the optic disc and temporal
raphe and to examine how these are related to test points in the 10-2 visual
field test pattern. SUBJECTS AND METHODS: For 22 eyes of volunteers with normal
vision (+0.75 D spherical equivalent 7.88 D), a volume scan was used to obtain en
face images from a plane fitted to the inner limiting membrane using optical
coherence tomography (OCT). The clearest en-face retinal nerve fibre (RNF) image
was chosen for each subject and superimposed on fundus photographs using blood
vessels for alignment. Individual landmarks (disc, fovea and visual field blind
spot) were then used to superimpose the Humphrey Field Analyzer 10-2 visual field
on the OCT image to compare with the RNF image. RESULTS: The average disc-fovea
raphe angle was 169.4 degrees +/-3.2 degrees . Both the disc and temporal raphe
were located above the horizontal midline (ie, were inferior in visual field
space). For the 10-2 test pattern superimposed on the OCT image, in 54.5% of
eyes, the temporal inferior test points adjacent to the horizontal midline mapped
to the anatomical inferior hemifield. In 22.7% of eyes, nasal inferior test
points adjacent to the horizontal midline mapped to the anatomical inferior
hemifield. This mapping is opposite to typically assumed. CONCLUSION: The
position of the disc and raphe affects the mapping between structure and function
with respect to superior and inferior hemifields. Individual differences in the
position of the temporal raphe should be considered when mapping between
structure and function for the 10-2 test pattern.
PMID- 28689168
TI - Systemic diseases in patients with HTLV-1-associated uveitis.
AB - BACKGROUND: Human T-lymphotropic virus type 1 (HTLV-1) carriers may develop
severe systemic diseases, such as adult T cell leukaemia (ATL) or HTLV-1
associated myelopathy/tropical spastic paraparesis (HAM/TSP). This study aims to
investigate systemic diseases of HTLV-1 carriers who had developed HTLV-1
associated uveitis (HAU). METHODS: We investigated the occurrence of systemic
diseases in 200 patients with HAU by performing a retrospective investigation of
their medical records and examining the results of a postal survey. RESULTS: The
mean age of HAU onset was 49 years, and the total person-years from HAU onset was
1627. There were two cases of ATL. Of these, one was diagnosed with smouldering
ATL at the time of HAU onset and the other developed acute-type ATL 4 years after
HAU onset. There were 26 cases of HAM/TSP; of these, HAM/TSP occurred first in 13
cases and HAU occurred first in 11 cases. The interval between the onset of
HAM/TSP and HAU ranged from 6 months to 6 years, with no significant difference
observed based on whether HAM/TSP or HAU occurred first. Hyperthyroidism was
noted in 45 cases and preceded onset in all cases. HAU onset occurred after
starting thiamazole treatment, and in two cases HAU recurred each time thiamazole
treatment was restarted. CONCLUSION: HTLV-1 carriers with HAU may develop HAM/TSP
more frequently than general carriers. HTLV-1 carriers undergoing treatment for
hyperthyroidism may be prone to developing HAU.
PMID- 28689170
TI - Late outcomes of gold weights and platinum chains for upper eyelid loading.
AB - AIM: To identify late outcomes of gold weights (GWs) and platinum chains (PCs)
for upper eyelid loading in the management of lagophthalmos. METHODS: A
retrospective case series of upper eyelid GWs and PCs at a single centre over a
10-year period (2004-2013). Two independent, blinded assessors graded standard
photographs for any weight-related morbidity (poor upper eyelid contour, weight
prominence and migration). RESULTS: Primary upper eyelid loading (high-tarsal
technique) was performed in 154 eyelids of 136 patients (facial nerve palsy,
n=99; non-paralytic, n=37). A total of 127 eyelids of 110 patients had primary GW
insertion. Of these, 40.9% (52/127) had revision surgery: exchange of GW for PC
(58%), GW repositioning (25%) and removal of GW (17%). Only 22.2% (6/27 eyelids)
with primary PCs required revision surgery. In those not requiring revision
surgery, photograph grading showed that both GWs and PCs had weight-related
morbidity at late follow-up (median=37.5 months, range 12-110 vs median=33.5
month, range 15-106). GWs had significantly higher rate of weight prominence
(p=0.001) and migration (p<0.001) compared with PCs. All PC revisions required
one procedure only compared with 10% of GWs revisions requiring two or more
procedures. Incidence of gold allergy was 7% (8/110 patients). There was no
association between the choice of weight material, physical weight or suture
material and eyelid morbidities. CONCLUSION: GWs were found to be associated with
higher complications and twice more likely to require long-term revision surgery
compared with PCs. Despite weight fixation at a high-tarsal location, prominence
of PCs can still occur.
PMID- 28689169
TI - Leber congenital amaurosis/early-onset severe retinal dystrophy: clinical
features, molecular genetics and therapeutic interventions.
AB - Leber congenital amaurosis (LCA) and early-onset severe retinal dystrophy (EOSRD)
are both genetically and phenotypically heterogeneous, and characterised
clinically by severe congenital/early infancy visual loss, nystagmus, amaurotic
pupils and markedly reduced/absent full-field electroretinograms. The vast
genetic heterogeneity of inherited retinal disease has been established over the
last 10 - 20 years, with disease-causing variants identified in 25 genes to date
associated with LCA/EOSRD, accounting for 70-80% of cases, with thereby more
genes yet to be identified. There is now far greater understanding of the
structural and functional associations seen in the various LCA/EOSRD genotypes.
Subsequent development/characterisation of LCA/EOSRD animal models has shed light
on the underlying pathogenesis and allowed the demonstration of successful rescue
with gene replacement therapy and pharmacological intervention in multiple
models. These advancements have culminated in more than 12 completed, ongoing and
anticipated phase I/II and phase III gene therapy and pharmacological human
clinical trials. This review describes the clinical and genetic characteristics
of LCA/EOSRD and the differential diagnoses to be considered. We discuss in
further detail the diagnostic clinical features, pathophysiology, animal models
and human treatment studies and trials, in the more common genetic subtypes
and/or those closest to intervention.
PMID- 28689171
TI - Acupuncture for the treatment of obesity in adults: a systematic review and meta
analysis.
AB - OBJECTIVE: Meta-analysis was used to assess the clinical efficacy of acupuncture
treatment for simple obesity and to provide evidence-based medical data for
treating obesity with acupuncture. METHODS: A comprehensive search of studies on
MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials and Chinese
databases (Wan Fang,CNKI and VIP) from 1 January 1915 through 30 November 2015
(MEDLINE search updated through 31 December 2015) was performed. We included only
randomised controlled trials (RCTs) that used acupuncture and sham acupuncture to
treat simple obesity. The effect of acupuncture on simple obesity was measured
using body mass index (BMI), body fat mass (BFM), waist circumference (WC), hip
circumference (HC), and body weight (BW). The Jadad scale was used to assess
methodological quality. The random effects model was used in the pooled analysis
to adjust for the heterogeneity of the included studies, and funnel plots were
used to examine publication bias. The differences between treatment groups were
reported as mean differences (MD). RESULTS: Eleven RCTs were selected after all
relevant literature from the electronic databases had been screened. There were
338 and 305 participants in the acupuncture and sham acupuncture groups,
respectively. Auricular and electro acupuncture were both able to reduce BMI in
obese patients (MD 0.47 kg/m2, 95% CI 0.35 to 0.58, p<0.001; MD 0.50 kg/m2, 95%
CI 0.38 to 0.62, p<0.001). BFM change after acupuncture treatment compared with
sham treatment was statistically significant (MD 0.66 kg, 95% CI 0.51 to 0.80,
p<0.001). There were also significant differences in WC and HC between the
acupuncture and sham acupuncture groups (MDwc2.02 cm, 95% CI 0.21 to 3.83,
p=0.03; MDHC2.74 cm, 95% CI 1.21 to 4.27, p=0.0004). BW was not statistically
significantly different between the acupuncture and sham acupuncture groups (MD
0.60 kg, 95% CI -0.20 to 1.39, p=0.14). Begg's test and funnel plots showed that
the potential publication bias of the included studies was very slight (p>0.05).
CONCLUSION: Acupuncture for simple obesity appeared to be an effective treatment,
but more studies on the safety of acupuncture used to treat simple obesity are
required.
PMID- 28689173
TI - Current understanding and management of pulmonary Langerhans cell histiocytosis.
AB - Pulmonary Langerhans cell histiocytosis (PLCH) is a diffuse lung disease that
usually affects young adult smokers. PLCH affects different lung compartments;
bronchiolar, interstitial and pulmonary vascular dysfunction may coexist to
varying extents, resulting in diverse phenotypes. Analyses of PLCH tissues have
identified activating mutations of specific mitogen-activated protein kinases
(BRAFV600E and others). The current consensus is that PLCH represents a myeloid
neoplasm with inflammatory properties: the myeloid tumour cells exhibit surface
CD1a expression and up to 50% of the cells harbour activating BRAF or other MAPK
mutations. PLCH may be associated with multisystem disease. The detection of
disease outside of the thorax is facilitated by whole body positron emission
tomography. The natural history of PLCH is unpredictable. In some patients,
disease may remit or stabilise following smoking cessation. Others develop
progressive lung disease, often associated with evidence of airflow limitation
and pulmonary vascular dysfunction. Due to the inability to accurately predict
the natural history, it is important that all patients undergo longitudinal
follow-up at least twice a year for the first few years following diagnosis. The
treatment of PLCH is challenging and should be individualised. While there is no
general consensus regarding the role of immunosuppression or chemotherapy in
management, selected patients may experience improvement in lung function with
therapy. Determination of BRAFV600E or other mutations may assist with the
development of an individualised approach to therapy. Patients with progressive
disease should be referred to specialised centres and considered for a trial of
pharmacotherapy or evaluated for transplantation.
PMID- 28689172
TI - Raw milk consumption and other early-life farm exposures and adult pulmonary
function in the Agricultural Lung Health Study.
AB - Literature suggests that early exposure to the farming environment protects
against atopy and asthma; few studies have examined pulmonary function. We
evaluated associations between early-life farming exposures and pulmonary
function in 3061 adults (mean age=63) from a US farming population using linear
regression. Childhood raw milk consumption was associated with higher FEV1
(beta=49.5 mL, 95% CI 2.8 to 96.1 mL, p=0.04) and FVC (beta=66.2 mL, 95% CI 13.2
to 119.1 mL, p=0.01). We did not find appreciable associations with other early
life farming exposures. We report a novel association between raw milk
consumption and higher pulmonary function that lasts into older adulthood.
PMID- 28689174
TI - Construct validity and test-retest reliability of the revised Upper Extremity
Work Demands (UEWD-R) Scale.
AB - BACKGROUND: The revised Upper Extremity Work Demand (UEWD-R) Scale is a six-item
self-report questionnaire to measure the workload of the upper limbs. UEWD-R
consists of a force/posture scale and a repetition scale. Psychometric properties
are unknown so far. PURPOSE: Assess the construct validity and the test-retest
reliability of UEWD-R. METHOD: Participants from different levels of physical
work demands (based on the Dictionary of Occupational Titles (DOT) categories)
were included. Construct validity was determined by testing 11 predefined
hypotheses regarding UEWD-R related to other constructs, including a workplace
observation using the Rapid Upper Limb Assessment (RULA). Correlations between
these measures were calculated using Spearman correlation coefficients. Test
retest reliability was determined using the intraclass correlation coefficient
(ICC) for agreement. The smallest detectable change (SDC) was calculated.
RESULTS: Fifty-four participants participated (63% men, mean age 39.4 years). The
four DOT categories were equally represented. Nine out of 11 predefined
correlations were confirmed (82%), indicating good construct validity. Strong
expected correlations of UEWD-R-total versus RULA-C (r=0.69) and UEWD-R
repetition versus RULA-muscle (r=0.12) were not confirmed. The test-retest
reliability was good (ICC agreement=0.79). The SDC was 4.85. CONCLUSION:
Construct validity and the test-retest reliability of UEWD-R were good. UEWD-R
can be used to evaluate the workload of the upper extremities. However, further
research is advised to assess the validity of the UEWD-R not only by testing
associations with RULA,but also with other observational measures.
PMID- 28689175
TI - Antiepileptic drug withdrawal risk calculator.
PMID- 28689176
TI - Providing experiential information on early medical abortion: a qualitative
evaluation of an animated personal account, Lara's Story.
AB - BACKGROUND: An animated film has been created to provide information to women
requesting early medical abortion (EMA). The 9 min film, Lara's Story, was
created using one woman's personal account of her experience. This study
evaluated the views of women who had recently undergone EMA on the film and its
potential usefulness in providing experiential information to women requesting
EMA. METHOD: Women who had undergone EMA within the past month were recruited.
They were shown the film and interviewed in a semi-structured style. Interviews
were recorded and transcribed verbatim. They were analysed using cross-sectional
indexing and thematic analysis with an inductive approach. RESULTS: 13 women were
interviewed. All reported that the film gave a realistic account of EMA and most
agreed that they would have wanted to watch it before EMA had it been available.
Some said that it might help women who were struggling with decision-making with
regard to EMA and all said that there should be unrestricted access to the film
from the website of the abortion service. The women commented that the animated
style of the film allowed all groups of women to relate to the story. Some
commented that Lara's experience of pain, bleeding and side effects such as
nausea differed from their own and therefore felt that it would be useful to make
more than one woman's account available. CONCLUSION: The availability of animated
audiovisual films recounting women's experiences of EMA might be a valuable
adjunct to clinical information for women seeking EMA.
PMID- 28689177
TI - Further thoughts on limitations, uncertainties and competing interpretations
regarding chemical exposures and diabetes.
PMID- 28689178
TI - Sacubitril/valsartan: beyond natriuretic peptides.
AB - Natriuretic peptides, especially B-type natriuretic peptide (BNP), have primarily
been regarded as biomarkers in heart failure (HF). However, they are also
possible therapeutic agents due to their potentially beneficial physiological
effects. The angiotensin receptor-neprilysin inhibitor, sacubitril/valsartan,
simultaneously augments the natriuretic peptide system (NPS) by inhibiting the
enzyme neprilysin (NEP) and inhibits the renin-angiotensin-aldosterone system
(RAAS) by blocking the angiotensin II receptor. It has been shown to improve
mortality and hospitalisation outcomes in patients with HF due to left
ventricular systolic dysfunction. The key advantage of sacubitril/valsartan has
been perceived to be its ability to augment BNP, while its other effects have
largely been overlooked. This review highlights the important effects of
sacubitril/valsartan, beyond just the augmentation of BNP. First we discuss how
NPS physiology differs between healthy individuals and those with HF by looking
at mechanisms like the overwhelming effects of RAAS on the NPS, natriuretic
peptide receptor desensitisation and absolute natriuretic deficiency. Second,
this review explores other hormones that are augmented by sacubitril/valsartan
such as bradykinin, substance P and adrenomedullin that may contribute to the
efficacy of sacubitril/valsartan in HF. We also discuss concerns that
sacubitril/valsartan may interfere with amyloid-beta homeostasis with potential
implications on Alzheimer's disease and macular degeneration. Finally, we explore
the concept of 'autoinhibition' which is a recently described observation that
humans have innate NEP inhibitory capability when natriuretic peptide levels rise
above a threshold. There is speculation that autoinhibition may provide a surge
of natriuretic and other vasoactive peptides to rapidly reverse decompensation.
We contend that by pre-emptively inhibiting NEP, sacubitril/valsartan is inducing
this surge earlier during decompensation, resulting in the better outcomes
observed.
PMID- 28689179
TI - Genetics and clinical response to warfarin and edoxaban in patients with venous
thromboembolism.
AB - OBJECTIVE: The aim of this study was to investigate whether genetic variants can
identify patients with venous thromboembolism (VTE) at an increased risk of
bleeding with warfarin. METHODS: Hokusai-venous thromboembolism (Hokusai VTE), a
randomised, multinational, double-blind, non-inferiority trial, evaluated the
safety and efficacy of edoxaban versus warfarin in patients with VTE initially
treated with heparin. In this subanalysis of Hokusai VTE, patients genotyped for
variants in CYP2C9 and VKORC1 genes were divided into three warfarin sensitivity
types (normal, sensitive and highly sensitive) based on their genotypes. An
exploratory analysis was also conducted comparing normal responders to pooled
sensitive responders (ie, sensitive and highly sensitive responders). RESULTS:
The analysis included 47.7% (3956/8292) of the patients in Hokusai VTE. Among
1978 patients randomised to warfarin, 63.0% (1247) were normal responders, 34.1%
(675) were sensitive responders and 2.8% (56) were highly sensitive responders.
Compared with normal responders, sensitive and highly sensitive responders had
heparin therapy discontinued earlier (p<0.001), had a decreased final weekly
warfarin dose (p<0.001), spent more time overanticoagulated (p<0.001) and had an
increased bleeding risk with warfarin (sensitive responders HR 1.38 [95% CI 1.11
to 1.71], p=0.0035; highly sensitive responders 1.79 [1.09 to 2.99]; p=0.0252).
CONCLUSION: In this study, CYP2C9 and VKORC1 genotypes identified patients with
VTE at increased bleeding risk with warfarin. TRIAL REGISTRATION NUMBER:
NCT00986154.
PMID- 28689180
TI - Structured group psychoeducation in patients with bipolar disorder delays time to
mania and time to any episode compared with a peer support group.
PMID- 28689181
TI - Subthreshold hypomania affects half of patients with bipolar disorder presenting
with depressive symptoms.
PMID- 28689182
TI - The importance of engaging users and measuring outcome for integrated care:
response to Ewing and Woodman.
PMID- 28689183
TI - Acute thrombus formation on phosphorilcholine surface modified flow diverters.
AB - PURPOSE: Thromboembolic complications remain a limitation of flow diverting
stents. We hypothesize that phosphorilcholine surface modified flow diverters
(Pipeline Flex with Shield Technology, sPED) would have less acute thrombus
formation on the device surface compared with the classic Pipeline Embolization
device (cPED). METHODS: Elastase-induced aneurysms were created in 40 rabbits and
randomly assigned to receive cPED or sPED devices with and without dual
antiplatelet therapy (DAPT) (four groups, n=10/group). Angioplasty was performed
to enhance apposition and create intimal injury for a pro-thrombotic environment.
Both before and after angioplasty, the flow diverter was imaged with
intravascular optical coherence tomography. The outcome measure was the number of
predefined segments along the implant relative to the location of the aneurysm
with a minimum of 0 (no clot formation) and maximum of 3 (all segments with
thrombus). Clot formation over the device at ostia of branch arteries was
assessed as either present or absent. RESULTS: Following angioplasty, the number
of flow diverter segments with clots was significantly associated with the flow
diverter (p<0.0001), but not with DAPT (p=0.3872) or aneurysm neck size
(p=0.8555). The incidence rate for clots with cPED was 1.72 times more than with
sPED. The clots on the flow diverter at the location corresponding to side branch
ostia was significantly lower with sPED than with cPED (OR 0.180; 95% CI 0.044 to
0.734; p=0.0168), but was not associated with DAPT (p=0.3198). CONCLUSION: In the
rabbit model, phosphorilcholine surface modified flow diverters are associated
with less thrombus formation on the surface of the device.
PMID- 28689184
TI - Evaluation of a novel liquid embolic agent (precipitating hydrophobic injectable
liquid (PHIL)) in an animal endovascular embolization model.
AB - BACKGROUND: The choice of the embolic agent and the embolization technique can
have a significant impact on the success of endovascular embolization. OBJECTIVE:
To evaluate a novel iodinated copolymer-based liquid embolic agent (precipitating
hydrophobic injectable liquid (PHIL)) in the porcine rete mirabile (RM), serving
as an endovascular embolization model. Onyx, as an established liquid embolic
agent, served as comparator. MATERIALS AND METHODS: Sixteen embolization
procedures were performed using PHIL (n=8) or Onyx (n=8) as liquid embolic agent.
Waiting time between injections was set to 30 or 60 s (n=4 per study group).
Survival time after intervention was 2 hours or 7 days. Embolization
characteristics (eg, procedure times, number of injections and volume of embolic
agent) and embolization extent (percentage of embolized RM in post-interventional
x-ray) were assessed. Post-interventional CT and histopathological analyses were
performed. RESULTS: Embolization characteristics and embolization extent were not
significantly different for PHIL and Onyx, including subgroups (eg, embolization
extent 44% vs 69% (medians); p=0.101). For PHIL, extension of the waiting time
from 30 to 60 s led to a significantly higher embolization extent (24% vs 72%
(medians); p=0.035). Moderate disintegration and mild inflammation of the
embolized blood vessels were present for both embolic agents. CONCLUSION: PHIL is
feasible for transarterial embolization in an acute and subacute endovascular
embolization model. In this preliminary experimental in vivo study, embolization
characteristics, embolization extent, and biocompatibility seem to be similar to
those of Onyx.
PMID- 28689185
TI - Patients' experiences of person-centred integrated heart failure care and
palliative care at home: an interview study.
AB - OBJECTIVES: Patients with severe heart failure (HF) suffer from a high symptom
burden and high mortality. European and Swedish guidelines for HF care recommend
palliative care for these patients. Different models for integrated palliative
care and HF care have been described in the literature. No studies were found
that qualitatively evaluated these models. The purpose of this study is to
describe patients' experiences of a new model of person-centred integrated HF and
palliative care at home. METHOD: Interviews were conducted with 12 patients with
severe HF (New York Heart Association class IIIa?"IV) and included in the
research project of Palliative advanced home caRE and heart FailurE caRe
(PREFER). Qualitative content analysis was used for data analysis. RESULTS: Two
themes and a total of five categories were identified. The first theme was
feeling secure and safe through receiving care at home with the categories:
having access to readily available care at home, being followed up continuously
and having trust in the team members' ability to help. The second theme was being
acknowledged as both a person and a patient, with the following two categories:
being met as a person, participating in decisions about one's care and receiving
help for symptoms of both HF and comorbidities. CONCLUSIONS: Person-centred
integrated HF and palliative care provides a secure environment and holistic care
for patients with severe HF. This approach is a way to improve the care
management in this population. TRIAL REGISTRATION NUMBER: NCT01304381; Results.
PMID- 28689186
TI - Acupuncture attenuates hyperglycaemia and improves ovarian function in female
rats subjected to continuous light exposure.
AB - OBJECTIVE: Exposure to unnatural light cycles is increasingly associated with
obesity and the metabolic syndrome. The purpose of this study was to examine the
effects of electroacupuncture (EA) on glucose metabolism and ovarian function in
female rats subjected to long-term continuous light exposure. METHODS: Female
Sprague-Dawley rats (n=24) were divided into three experimental groups: an LD
group that was maintained under a normal light-dark cycle (healthy control); an
LL group that was exposed to continuous light for 21 weeks but remained
untreated; and an LL+EA group that received EA at ST36 and SP6 during weeks 17 to
21 of continuous light exposure. RESULTS: Oestrous cycles of female rats kept in
a continuously lit environment for 21 weeks were disordered and polycystic
ovarian syndrome (PCOS)-like changes occurred, accompanied by increased fasting
blood glucose (6.23+/-0.33 vs 5.27+/-0.40 mmol/L in week 17, p=0.015) and reduced
fasting levels of serum testosterone (0.07+/-0.018 vs 0.12+/-0.058 ng/L, p=0.043)
and insulin (0.89+/-0.20 vs 1.43+/-0.46 ng/L, p=0.006). After 5 weeks of EA
treatment at ST36 and SP6, ovarian cycle disruption was mitigated and blood
glucose levels showed a gradual decline (5.18+/-0.37 vs 5.80+/-0.55 mmol/L,
p=0.017; and 5.73+/-0.31 vs 6.62+/-0.13 mmol/L, p=0.004; in the fourth and fifth
weeks of EA treatment, respectively). EA also attenuated the reductions otherwise
seen in serum insulin and testosterone levels. CONCLUSION: Prolonged exposure to
light can lead to a decline in ovarian and pancreatic function. EA at ST36 and
SP6 may reduce abnormally elevated blood glucose levels and improve ovarian and
pancreatic hormone levels.
PMID- 28689187
TI - Acupuncture for the treatment of gastro-oesophageal reflux disease: a systematic
review and meta-analysis.
AB - BACKGROUND: Gastro-oesophageal reflux disease (GORD) is one of the most common
diseases presenting to gastroenterology clinics. Acupuncture is widely used as a
complementary and alternative treatment for patients with GORD. OBJECTIVE: To
explore the effectiveness of acupuncture for the treatment of GORD. METHODS: Four
English and four Chinese databases were searched through June 2016. Randomised
controlled trials investigating the effectiveness of manual acupuncture or
electroacupuncture (MA/EA) for GORD versus or as an adjunct to Western medicine
(WM) were selected. Data extraction and quality evaluation were performed by two
authors independently and RevMan 5.2.0 was used to analyse data. RESULTS: A total
of 12 trials involving 1235 patients were included. Meta-analyses demonstrated
that patients receiving MA/EA combined with WM had a superior global symptom
improvement compared with those receiving WM alone (relative risk (RR) 1.17, 95%
CI 1.09 to 1.26; p=0.03; six studies) with no significant heterogeneity (I2=0%,
p=0.41). Recurrence rates of those receiving MA/EA alone were lower than those
receiving WM (RR 0.42,95% CI 0.29 to 0.61; p<0.001; three studies) with low
heterogeneity (I2=7%, p=0.34), while global symptom improvement (six studies) and
symptom scores (three studies) were similar (both p>0.05). Descriptive analyses
suggested that acupuncture also improves quality of life in patients with GORD.
CONCLUSION: This meta-analysis suggests that acupuncture is an effective and safe
treatment for GORD. However, due to the small sample size and poor methodological
quality of the included trials, further studies are required to validate our
conclusions. TRIAL REGISTRATION NUMBER: PROSPERO Systematic review registration
no. CRD42016041916.
PMID- 28689188
TI - Beverage Intake During Pregnancy and Childhood Adiposity.
AB - OBJECTIVES: To examine associations of sugar sweetened beverages (SSBs) and other
beverage intake during pregnancy with adiposity in midchildhood (median age of
7.7 years). METHODS: We studied 1078 mother-child pairs in Project Viva, a
prospective prebirth cohort study. Exposures were sugary and nonsugary beverage
intake assessed in the first and second trimesters of pregnancy by using a food
frequency questionnaire. Main outcome measures were offspring overall adiposity
(BMI z score, fat mass index [FMI, kg/m2] from dual-energy radiograph
absorptiometry, and sum of subscapular [SS] and triceps [TR] skinfold
thicknesses) and central adiposity (SS:TR ratio and waist circumference).
RESULTS: In the second trimester, mean (SD) SSB intake was 0.6 (0.9) servings per
day. Thirty-two percent of mothers were multiracial or people of color, 68% were
college graduates, and 10% smoked during pregnancy. In midchildhood, mean (SD)
BMI z score was 0.38 (1.00), and the FMI was 4.4 (1.9) kg/m2. In multivariable
models adjusted for multiple maternal and child covariates, each additional
serving per day of SSB was associated with higher BMI z scores (0.07 U; 95%
confidence interval [CI]: -0.01 to 0.15), FMI (0.15 kg/m2; 95% CI: -0.01 to
0.30), SS + TR (0.85 mm; 95% CI: 0.06 to 1.64), and waist circumference (0.65 cm;
95% CI: 0.01 to 1.28). Stratified models suggested that the associations were due
primarily to maternal, not child, SSB intake and to sugary soda rather than fruit
drinks or juice. We did not find differences between boys and girls, nor did we
observe the effects of sugar-free soda or of first-trimester beverage intake.
CONCLUSIONS: Higher SSB intake during the second trimester of pregnancy was
associated with greater adiposity in midchildhood.
PMID- 28689189
TI - Early Hearing Detection and Vocabulary of Children With Hearing Loss.
AB - BACKGROUND AND OBJECTIVES: To date, no studies have examined vocabulary outcomes
of children meeting all 3 components of the Early Hearing Detection and
Intervention (EHDI) guidelines (hearing screening by 1 month, diagnosis of
hearing loss by 3 months, and intervention by 6 months of age). The primary
purpose of the current study was to examine the impact of the current EHDI 1-3-6
policy on vocabulary outcomes across a wide geographic area. A secondary goal was
to confirm the impact of other demographic variables previously reported to be
related to language outcomes. METHODS: This was a cross-sectional study of 448
children with bilateral hearing loss between 8 and 39 months of age (mean = 25.3
months, SD = 7.5 months). The children lived in 12 different states and were
participating in the National Early Childhood Assessment Project. RESULTS: The
combination of 6 factors in a regression analysis accounted for 41% of the
variance in vocabulary outcomes. Vocabulary quotients were significantly higher
for children who met the EHDI guidelines, were younger, had no additional
disabilities, had mild to moderate hearing loss, had parents who were deaf or
hard of hearing, and had mothers with higher levels of education. CONCLUSIONS:
Vocabulary learning may be enhanced with system improvements that increase the
number of children meeting the current early identification and intervention
guidelines. In addition, intervention efforts need to focus on preventing
widening delays with chronological age, assisting mothers with lower levels of
education, and incorporating adults who are deaf/hard-of-hearing in the
intervention process.
PMID- 28689190
TI - Intermediate C9orf72 alleles in neurological disorders: does size really matter?
AB - C9orf72 repeat expansions is a major cause of familial frontotemporal dementia
(FTD) and amyotrophic lateral sclerosis (ALS) worldwide. Sizes of <20
hexanucleotide repeats are observed in controls, while up to thousands associate
with disease. Intermediate C9orf72 repeat lengths, however, remain uncertain. We
systematically reviewed the role of intermediate C9orf72 alleles in C9orf72
related neurological disorders. We identified 49 studies with adequate available
data on normal or intermediate C9orf72 repeat length, involving subjects with
FTD, ALS, Parkinson's disease (PD), atypical parkinsonism, Alzheimer's disease
(AD) and other aetiologies. We found that, overall, normal or intermediate
C9orf72 repeat lengths are not associated with higher disease risk across these
disorders, but intermediate allele sizes appear to associate more frequently with
neuropsychiatric phenotypes. Intermediate sizes were detected in subjects with
personal or family history of FTD and/or psychiatric illness, parkinsonism
complicated by psychosis and rarely in psychiatric cohorts. Length of the
hexanucleotide repeat may be influenced by ethnicity (with Asian controls
displaying shorter normal repeat lengths compared with Caucasians) and underlying
haplotype, with more patients and controls carrying the 'risk' haplotype
rs3849942 displaying intermediate alleles. There is some evidence that
intermediate alleles display increased methylation levels and affect normal
transcriptional activity of the C9orf72 promoter, but the 'critical' repeat size
required for initiation of neurodegeneration remains unknown and requires further
study. In common neurological diseases, intermediate C9orf72 repeats do not
influence disease risk but may associate with higher frequency of
neuropsychiatric symptoms. This has important clinical relevance as intermediate
carriers pose a challenge for genetic counselling.
PMID- 28689191
TI - How do hospital boards govern for quality improvement? A mixed methods study of
15 organisations in England.
AB - BACKGROUND: Health systems worldwide are increasingly holding boards of
healthcare organisations accountable for the quality of care that they provide.
Previous empirical research has found associations between certain board
practices and higher quality patient care; however, little is known about how
boards govern for quality improvement (QI). METHODS: We conducted fieldwork over
a 30-month period in 15 healthcare provider organisations in England as part of a
wider evaluation of a board-level organisational development intervention. Our
data comprised board member interviews (n=65), board meeting observations (60
hours) and documents (30 sets of board meeting papers, 15 board minutes and 15
Quality Accounts). We analysed the data using a framework developed from existing
evidence of links between board practices and quality of care. We mapped the
variation in how boards enacted governance of QI and constructed a measure of QI
governance maturity. We then compared organisations to identify the
characteristics of those with mature QI governance. RESULTS: We found that boards
with higher levels of maturity in relation to governing for QI had the following
characteristics: explicitly prioritising QI; balancing short-term (external)
priorities with long-term (internal) investment in QI; using data for QI, not
just quality assurance; engaging staff and patients in QI; and encouraging a
culture of continuous improvement. These characteristics appeared to be
particularly enabled and facilitated by board-level clinical leaders.
CONCLUSIONS: This study contributes to a deeper understanding of how boards
govern for QI. The identified characteristics of organisations with mature QI
governance seemed to be enabled by active clinical leadership. Future research
should explore the biographies, identities and work practices of board-level
clinical leaders and their role in organisation-wide QI.
PMID- 28689192
TI - Utilizing a transfer of care bundle to reduce unplanned readmissions to the
cardiac intensive care unit.
PMID- 28689193
TI - Anticipation, teamwork and cognitive load: chasing efficiency during robot
assisted surgery.
AB - INTRODUCTION: Robot-assisted surgery (RAS) has changed the traditional operating
room (OR), occupying more space with equipment and isolating console surgeons
away from the patients and their team. We aimed to evaluate how anticipation of
surgical steps and familiarity between team members impacted efficiency. METHODS:
We analysed recordings (video and audio) of 12 robot-assisted radical
prostatectomies. Any requests between surgeon and the team members were
documented and classified by personnel, equipment type, mode of communication,
level of inconvenience in fulfilling the request and anticipation. Surgical team
members completed questionnaires assessing team familiarity and cognitive load
(National Aeronautics and Space Administration - Task Load Index). Predictors of
team efficiency were assessed using Pearson correlation and stepwise linear
regression. RESULTS: 1330 requests were documented, of which 413 (31%) were
anticipated. Anticipation correlated negatively with operative time, resulting in
overall 8% reduction of OR time. Team familiarity negatively correlated with
inconveniences. Anticipation ratio, per cent of requests that were non-verbal and
total request duration were significantly correlated with the console surgeons'
cognitive load (r=0.77, p=0.006; r=0.63, p=0.04; and r=0.70, p=0.02,
respectively). CONCLUSIONS: Anticipation and active engagement by the surgical
team resulted in shorter operative time, and higher familiarity scores were
associated with fewer inconveniences. Less anticipation and non-verbal requests
were also associated with lower cognitive load for the console surgeon. Training
efforts to increase anticipation and team familiarity can improve team efficiency
during RAS.
PMID- 28689195
TI - Clouds.
PMID- 28689194
TI - Risk factors and outcomes associated with post-traumatic headache after mild
traumatic brain injury.
AB - OBJECTIVES: To determine the prevalence and potential risk factors of acute and
chronic post-traumatic headache (PTH) in patients with mild to moderate traumatic
brain injury (TBI) in a prospective longitudinal observational multicentre study.
Acute PTH (aPTH) is defined by new or worsening of pre-existing headache
occurring within 7 days after trauma, whereas chronic PTH (cPTH) is defined as
persisting aPTH >3 months after trauma. An additional goal was to study the
impact of aPTH and cPTH in terms of return to work (RTW), anxiety and depression.
METHODS: This was a prospective observational study conducted between January
2013 and February 2014 in three trauma centres in the Netherlands. Patients aged
16 years and older with a GCS score of 9-15 on admission to the ED, with loss of
consciousness and/or amnesia were prospectively enrolled. Follow-up
questionnaires were completed at 2 weeks and 3 months after injury with the Head
Injury Symptom Checklist, the Hospital Anxiety and Depression Scale and RTW
scale. RESULTS: In total, 628 patients were enrolled in the study, 469 completed
the 2-week questionnaire (75%) at 2 weeks and 409 (65%) at 3 months. At 2 weeks,
238 (51%) had developed aPTH and at 3 months 95 (23%) had developed cPTH. Female
gender, younger age, headache immediately at the ED and CT scan abnormalities
increased the risk for aPTH. Risk factors for cPTH were female gender and
headache at the ED. Patients with cPTH were less likely to have returned to work
than those without cPTH (35% vs 14%, P=0.001). Patients with aPTH and cPTH more
often report anxiety (20% and 28%, P=0.001) and depression (19% and 28%, P=0.001)
after trauma in comparison with the group without PTH (10% anxiety and 8%
depression). CONCLUSIONS: PTH is an important health problem with a significant
impact on long-term outcome of TBI patients. Several risk factors were
identified, which can aid in early identification of subjects at risk for PTH.
PMID- 28689196
TI - Love as delusion, delusions of love: erotomania, narcissism and shame.
AB - Erotomania has a long, colourful history in psychiatry. It is a rare condition in
which the patient ('subject') develops the belief that he or she is loved from
afar by another person ('object'). The subject is generally female, though men
predominate in forensic samples. The object is generally perceived to belong to a
higher social class, reflecting a sociopolitical element in the construction of
love. Erotomania requires active treatment and risk management as it can be
associated with stalking and other offending behaviour. In addition to featuring
in the psychiatry literature, erotomania features in the biography of the
economist John Maynard Keynes (the apparent 'object' of a woman's erotomanic
delusions in the early 1900s) and in fiction (eg, Ian McEwan's Enduring Love);
this reflects, in part, the general popularity of romantic themes in broader
literature and society. In psychological terms, certain cases of erotomania might
be underpinned by combinations of longing, disappointment, shame and narcissism
in specific social contexts. Lesser forms of delusional exaggeration of true love
might also exist in some stable relationships, and might even be essential for
their continued existence. Overall, the division between love and delusions of
love is not as distinct as one might imagine. The potential presence of an
element of delusional love in many relationships might well serve important
social functions, conferring specific advantages on the parties involved and
increasing social and community stability. After all, delusions persist; love
dies.
PMID- 28689198
TI - Influence of the Method of Definition on the Prevalence of Left-Ventricular
Hypertrophy in Children with Chronic Kidney Disease: Data from the Know-Ped CKD
Study.
AB - BACKGROUND/AIMS: Children with chronic kidney disease (CKD) have a high risk of
cardiovascular disease. Left-ventricular (LV) hypertrophy (LVH) is an early
marker of cardiovascular disease in pediatric CKD, and the prevalence of LVH in
pediatric CKD is approximately 20-30% in pre-dialysis CKD patients. However,
there is no consensus on the ideal method of defining LVH in pediatric CKD
patients. Previous studies have typically used the LV mass index (LVMI), which is
calculated as LV mass in grams divided by height in meters to the 2.7th power >=
38 g/m2.7, to diagnose LVH in children with CKD. Recently, age-specific reference
values for LVMI >= 95th percentile and LV wall-thickness z-score > 1.64 in
children were addressed. The aim of this study was to assess the prevalence and
contributing factors of LVH in pediatric CKD patients according to each
measurement and evaluate the concordance between each measurement. METHODS: We
used the baseline data of the KoreaN cohort study for Outcome in patients With
Pediatric Chronic Kidney Disease (KNOW-Ped CKD), which is a nationwide, 10-year,
prospective, observational cohort study of pediatric CKD. A total of 469 patients
were enrolled, and 458 patients were included in the final analysis. Univariate
and multiple logistic regression analysis were performed to evaluate the
association of the variables with LVH. Kappa statistics were used to analyze the
concordance. RESULTS: According to an LVH diagnosis of LVMI >= 38 g/m2.7, 188
patients (41.0%) were diagnosed with LVH, and the prevalence of LVH was high in
younger patients (< 2 years of age). Using the age-specific reference values, 116
patients (25.3%) were diagnosed with LVH, and there was no difference in the
prevalence of LVH according to age. Thirty-one patients (6.8%) were diagnosed
with LVH using an LV wall-thickness z-score > 1.64. There is poor concordance
between the diagnosis of LVH using the LV wall-thickness z-score and the LVMI
method. CONCLUSIONS: The results of this study show that there is poor
concordance between the diagnosis of LVH using the wall-thickness z-score and the
LVMI2.7 criteria. Further investigation is needed to estimate the correlation
between LVH and cardiac dysfunction and to find a better method for defining LVH
in the pediatric CKD cohort and thereby predicting cardiac dysfunction.
PMID- 28689199
TI - Photoacoustic Imaging: A Novel Tool for Detecting Carotid Artery Thrombosis in
Mice.
AB - Thrombosis is a main cause of acute cardiovascular events, and detecting thrombi
in small arteries via noninvasive imaging remains challenging. In this study, we
employed a novel imaging method, photoacoustic imaging (PAI), to study thrombosis
in a mouse model of ferric chloride (FeCl3)-induced arterial thrombosis and
compared the ability of this method to detect thrombosis with that of a
conventional imaging method, namely, ultrasound. The mice (n = 20) were divided
equally into the following 4 groups: (1) a normal group, and (2) 3 experimental
groups, in which the left common carotid artery was treated with 20% FeCl3 for 1,
3, or 5 min, respectively. After 24 h, PAI detected thrombi of different sizes
and generated images, enabling us to assess the changes in structure. The results
of this study suggest that PAI is a useful, noninvasive visualization tool for
investigating the mechanism underlying thrombosis development and is suitable for
imaging arterial thrombosis in mouse carotid arteries.
PMID- 28689200
TI - Optimal Medical Management Reduces Risk of Disease Progression and Ischemic
Events in Asymptomatic Carotid Stenosis Patients: A Long-Term Follow-Up Study.
AB - BACKGROUND AND PURPOSE: To assess the effect of optimal medical management
including atherosclerotic risk factor control on ischemic stroke (IS), transient
ischemic attack (TIA), carotid revascularization (CRV), and progression of
severity of carotid stenosis (PSCS) in patients with asymptomatic carotid artery
stenosis (ACAS). METHODS: We conducted a retrospective analysis of patients with
ACAS (who had at least 3 serial carotid duplex ultrasounds) for incidence of IS,
TIA, and PSCS. RESULTS: Eight hundred sixty-four patients with a mean follow-up
duration of 79 +/- 36 months were included. IS/TIA and CRV occurred in 12.2% of
the patients and PCSS was observed in 21.5% vessels. On univariate analysis it
was found that low-density lipoprotein (LDL) levels >100 mg/dL, no statin or low
potency statins, average systolic blood pressure (SBP) >=140 mm Hg and/or
diastolic blood pressure (DBP) >=90 mm Hg and history of smoking were predictors
of the combined endpoint of IS/TIA/CRV and PSCS. On multivariate analysis, it was
found that LDL >100 mg/dL, no statin or low-potency statin, SBP >=140 mm Hg
and/or DBP >=90 mm Hg, and Hx of smoking were independent predictors of PSCS.
Similarly no statin or low-potency statin, SBP >=140 mm Hg and/or DBP >=90 mm Hg,
Hx of atrial fibrillation/flutter, Hx of chronic kidney disease, and PSCS were
independent predictors of IS/TIA. No statin or low-potency statin, SBP >=140 mm
Hg and/or DBP >=90 mm Hg, diabetes mellitus, baseline carotid artery stenosis
>=70%, and PSCS were found to be independent predictors of combined endpoint
IS/TIA and CRV. CONCLUSION: Intensive medical therapy in the patients with ACAS
results in lower incidence of IS/TIA, CRV, and PSCS with a significant
incremental beneficial effect.
PMID- 28689201
TI - The Effects of Human Beta-Defensins on Skin Cells in vitro.
AB - BACKGROUND: Defensins are antimicrobial peptides that exert immunomodulatory and
chemotactic functions. Based on these properties and their high expression levels
in the skin, they are likely to affect skin inflammation, infection, and wound
healing. This may lead to therapeutic applications in (burn) wound healing.
OBJECTIVE: We aimed to investigate the effects of human beta-defensins (hBDs) on
keratinocytes and fibroblasts, 2 major skin cell types involved in skin
regeneration. METHODS: Monolayer keratinocyte and fibroblast cultures were
exposed to recombinant hBDs, and we overexpressed hBD2 and hBD3 in keratinocytes
of reconstructed epidermal equivalents by lentiviral transduction. The effects
were measured by immunohistochemistry, quantitative real-time PCR, and migration
assays. Kinome analyses were performed on cultured keratinocytes to investigate
the signal transduction events elicited by hBD stimulation. RESULTS: We found
that hBD3 induced the expression of cytokines and chemokines in keratinocytes,
which was not observed in fibroblasts. hBD2, however, stimulated cell migration
only in fibroblasts, which was not found for hBD3. Both defensins are likely to
exert receptor-mediated effects in keratinocytes, as witnessed by changes in
protein kinase activation following stimulation by hBD2 and hBD3. Kinome analysis
suggested that protein kinase C activation was a common event for both defensins.
We observed, however, considerable differences in keratinocyte responses between
stimulation by exogenous recombinant defensins and endogenous defensins expressed
following lentiviral transduction. CONCLUSION: Defensins exert modest biological
effects on skin cells that are potentially beneficial in wound healing, but many
questions regarding the biological mechanisms of action and relevance for the in
vivo situation are still remaining.
PMID- 28689204
TI - A Vexing CA 125 Raise in a Patient with Pleural Effusion and Ovarian Cancer.
PMID- 28689203
TI - Global Application of the Assessment of Communication Skills of Paediatric
Endocrinology Fellows in the Management of Differences in Sex Development Using
the ESPE E-Learning.Org Portal.
AB - BACKGROUND: Information sharing in chronic conditions such as disorders
of/differences in sex development (DSD) is essential for a comprehensive
understanding by parents and patients. We report on a qualitative analysis of
communication skills of fellows undergoing training in paediatric endocrinology.
Guidelines are created for the assessment of communication between health
professionals and individuals with DSD and their parents. METHODS: Paediatric
endocrinology fellows worldwide were invited to study two interactive online
cases (www.espe-elearning.org) and to describe a best practice communication with
(i) the parents of a newborn with congenital adrenal hyperplasia and (ii) a young
woman with 46,XY gonadal dysgenesis. The replies were analysed regarding
completeness, quality, and evidence of empathy. Guidelines for structured
assessment of responses were developed by 22 senior paediatric endocrinologists
worldwide who assessed 10 selected replies. Consensus of assessors was
established and the evaluation guidelines were created. RESULTS: The replies of
the fellows showed considerable variation in completeness, quality of wording,
and evidence of empathy. Many relevant aspects of competent clinical
communication were not mentioned; 15% (case 1) and 17% (case 2) of the replies
were considered poor/insufficient. There was also marked variation between 17
senior experts in the application of the guidelines to assess communication
skills. The guidelines were then adjusted to a 3-level assessment with empathy as
a separate key item to better reflect the qualitative differences in the replies
and for simplicity of use by evaluators. CONCLUSIONS: E-learning can play an
important role in assessing communication skills. A practical tool is provided to
assess how information is shared with patients with DSD and their families and
should be refined by all stakeholders, notably interdisciplinary health
professionals and patient representatives.
PMID- 28689205
TI - Genomics in Primary and Secondary Prevention of Pancreatic Cancer.
AB - BACKGROUND: Pancreatic cancer (PC) is one of the deadliest cancers worldwide for
which little clinical progress has been made in the last decades. Furthermore,
increased trends of PC mortality rates have been reported in Westernised
countries. PC is usually diagnosed in advanced stages, precluding patients of an
effective treatment. Identifying high-risk populations and early detection
markers is the first and crucial step to impact on these figures and change the
PC horizon. AIMS/OBJECTIVES: To discuss the published body of evidence on host
and tumor genomics promising markers for primary and/or secondary personalised PC
prevention, as well as the future perspectives in the field. METHODS: A review of
the literature was performed to identify germline and tumor DNA and RNA markers
that showed potential usefulness in defining the high-risk population, diagnosing
the disease early, and identifying new carcinogens associated with PC. RESULTS:
Only high-penetrance inherited mutations are used, at present, to define the high
risk PC population. Although there are some promising genomics markers to be used
as early detection tests, none has been validated adequately to be integrated
into the clinics routine. CONCLUSIONS: Despite of important efforts made in the
recent time, little progress has been made to better characterise high-risk PC
populations and to identify genomics-based markers for its early diagnosis. PC
rates continue to rise, and this disease is becoming a real public health problem
in the Westernised world. International and multidisciplinary strategies to
identify new markers and properly validate the promising ones are urgently needed
to implement cost-efficient primary and secondary prevention interventions in PC.
PMID- 28689206
TI - Guide for Current Nutrigenetic, Nutrigenomic, and Nutriepigenetic Approaches for
Precision Nutrition Involving the Prevention and Management of Chronic Diseases
Associated with Obesity.
AB - Chronic diseases, including obesity, are major causes of morbidity and mortality
in most countries. The adverse impacts of obesity and associated comorbidities on
health remain a major concern due to the lack of effective interventions for
prevention and management. Precision nutrition is an emerging therapeutic
approach that takes into account an individual's genetic and epigenetic
information, as well as age, gender, or particular physiopathological status.
Advances in genomic sciences are contributing to a better understanding of the
role of genetic variants and epigenetic signatures as well as gene expression
patterns in the development of diverse chronic conditions, and how they may
modify therapeutic responses. This knowledge has led to the search for genetic
and epigenetic biomarkers to predict the risk of developing chronic diseases and
personalizing their prevention and treatment. Additionally, original nutritional
interventions based on nutrients and bioactive dietary compounds that can modify
epigenetic marks and gene expression have been implemented. Although caution must
be exercised, these scientific insights are paving the way for the design of
innovative strategies for the control of chronic diseases accompanying obesity.
This document provides a number of examples of the huge potential of
understanding nutrigenetic, nutrigenomic, and nutriepigenetic roles in precision
nutrition.
PMID- 28689207
TI - Design of Finasteride-Loaded Nanoparticles for Potential Treatment of Alopecia.
AB - BACKGROUND/AIMS: Androgenetic alopecia is an extremely common dermatological
disorder affecting both men and women. Oral finasteride (FNS), a synthetic 4-aza
3-oxosteroid compound with poor aqueous solubility, blocks the peripheral
conversion of testosterone to dihydrotestosterone (DHT) in a significant
reduction in DHT concentration, achieving satisfactory results in alopecia
treatment. However, its oral intake generally causes severe side effects.
Considering that there is currently no scientifically proven treatment, new drug
delivery systems able to improve alopecia therapy are urgently required. METHODS:
In this study, polymeric nanoparticles have been proposed as a new carrier for
topical delivery of FNS in hair follicles. RESULTS AND CONCLUSIONS: Polymeric
nanoparticles, prepared by using a modified method of the emulsification/solvent
diffusion, showed a mean particle size around 300 nm, which may be sufficient for
reaching the dermis and hair follicles and negative zeta potential values.
Scanning electron microscope measurements showed that all the polymeric
nanoparticles exhibited a spherical shape and a smooth surface regardless of
their composition. A high encapsulation efficiency was achieved for FNS (79.49 +/
0.47%). In vitro release assays in physiological conditions demonstrated that
nanoparticles yielded a prolonged release of FNS for 3 h. Skin assays through an
in vitro permeation study demonstrated that nanoparticles had low levels of
penetration of FNS, improving its time residence onto the skin. All excipients
used in nanoparticle composition and in 3 different vehicles were safe. These
results suggest that the proposed novel formulation presents several good
characteristics indicating its suitability for dermal delivery of FNS for
alopecia treatment.
PMID- 28689208
TI - Staging with Unilateral Salpingo-Oophorectomy and Expert Pathological Review
Result in No Recurrences in a Series of 81 Intestinal-Type Mucinous Borderline
Ovarian Tumors.
AB - OBJECTIVE: Recent studies suggest that mucinous borderline ovarian tumors (MBOTs)
belong to a high-risk group that is more likely to develop an invasive
recurrence. The objective is to determine these risk factors. METHODS: A
monocentric retrospective review of all consecutive patients with intestinal-type
MBOT diagnosed between 1993 and 2013. All tumors were evaluated by one
pathologist without knowledge of clinical outcome. Extensive surgical staging and
pathological tumor sampling (1 block/cm diameter in tumors <10 cm and 2 blocks/cm
diameter in tumors >10 cm) were performed in all cases. RESULTS: A total of 81
patients were included. Patients with micro-invasion were also included. None of
the patients recurred. No bilateral tumors, nor tumors with International
Federation of Gynecology and Obstetrics stage II or higher, were diagnosed.
Median follow-up was 87 months. CONCLUSIONS: In our series of pure intestinal
type MBOT, including micro-invasion, no recurrences were observed. Given the
heterogeneity of these tumors staging with at least unilateral salpingo
oophorectomy, extensive pathological sampling, and expert pathological review are
of paramount importance to be able to diagnose a pure intestinal-type MBOT and
excluding gastrointestinal mucinous tumors and more important, excluding an
invasive focus, defining a mucinous ovarian carcinoma. When these conditions are
fulfilled, the prognosis of pure intestinal-type MBOT is excellent.
PMID- 28689209
TI - Association Between Hepatocellular Carcinoma and Type 2 Diabetes Mellitus in
Chinese Hepatitis B Virus Cirrhosis Patients: A Case-Control Study.
AB - BACKGROUND Whether the presence of type 2 diabetes mellitus (T2DM) increases the
risk of hepatocellular carcinoma (HCC) in hepatitis B virus (HBV) cirrhosis
patients is controversial. We conducted a retrospective case-control study to
evaluate this issue. MATERIAL AND METHODS We considered all patients diagnosed
with HBV-related liver cirrhosis at our hospital from July 2011 to June 2014. The
case (n=91) and control (n=91) groups were HBV cirrhosis patients with and
without T2DM, respectively. They were matched at a ratio of 1: 1 according to the
individual age (+/-2 years) and same sex and Child-Pugh score. RESULTS None of
the baseline data were significantly different between the 2 groups. The
percentage of HCC was similar between the 2 groups (case versus control group:
34.1% versus 46.2%, P=0.13). In the case group, sex (P=0.002), alkaline
phosphatase (P<0.001), g-glutamine transferase (P=0.001), and sodium (P=0.003)
were associated with the risk of HCC. In the control group, platelet (P=0.041),
alanine aminotransferase (P=0.034), aspartate aminotransferase (P=0.026),
alkaline phosphatase (P<0.001), and gamma-glutamine transferase (P<0.001) were
associated with the risk of HCC. CONCLUSIONS T2DM may not be a risk factor for
the presence of HCC in HBV cirrhosis.
PMID- 28689210
TI - Residential Air Pollution, Road Traffic, Greenness and Maternal Hypertension:
Results from GINIplus and LISAplus.
AB - BACKGROUND: The public health burden of hypertension is high, but its
relationship with long-term residential air pollution, road traffic, and
greenness remains unclear. OBJECTIVE: To investigate associations between
residential air pollution, traffic, greenness, and hypertension among mothers.
METHODS: Information on doctor-diagnosed maternal hypertension was collected at
the 15-year follow-up of two large population-based multicenter German birth
cohorts-GINIplus and LISAplus (n=3063). Residential air pollution was modelled by
land use regression models within the ESCAPE and universal kriging within the
APMoSPHERE projects. Road traffic was defined as traffic load on major roads
within a 100-m buffer around residences. Vegetation level (ie, greenness) was
defined as the mean Normalized Difference Vegetation Index in a 500-m buffer
around residences and was assessed from Landsat 5 TM satellite images. All the
exposure variables were averaged over three residential addresses during the last
10 years and categorized into tertiles or dichotomized. The individual
associations between each of the exposure variables and hypertension were
assessed using logistic regression analysis. RESULTS: No significant and
consistent associations across different levels of adjustment were observed
between the exposures of interest and hypertension. The only significant estimate
was found with coarse particulate matter concentrations (OR 1.66, 95% CI 1.01 to
2.74; 3rdvs 1st tertile) among mothers residing in the Wesel area. No significant
associations were observed with traffic load or greenness. CONCLUSION: This study
does not provide evidence on detrimental effects of air pollution and road
traffic or beneficial effects of greenness on hypertension among German adults.
PMID- 28689211
TI - Association between Air Temperature and Acute Myocardial Infarction
Hospitalizations in Tehran, Iran: A Time-Stratified Case-Crossover.
AB - BACKGROUND: Although the effect of temperature on the incidence of acute
myocardial infarction (AMI) has been extensively documented, no study has
previously investigated the association between temperature and AMI in the Middle
Eastern countries. OBJECTIVE: To examine the association between daily mean
temperature and AMI admission rates in Tehran, Iran. METHODS: Data on daily
number of admissions of patients with AMI to Tehran hospitals between March 21,
2013 and March 19, 2016, were retrieved from the Iranian Myocardial Infarction
Registry (IMIR). Over the same period, data on daily mean temperature and
relative humidity were measured at Mehrabad International Airport weather station
of the Islamic Republic of Iran Meteorological Organization. Time-stratified case
crossover design was employed to investigate the short-term association between
the daily mean temperature and the number of daily admissions of patients with
AMI, after adjusting for public holidays, relative humidity, and air pollution.
RESULTS: An interquartile range (IQR) increase in daily mean temperature was
associated with 15.1% (95% CI 1.3 to 30.8%) and 13% (95% CI 1.9% to 25.4%)
increase in the risk of AMI hospitalizations during the entire year, and in the
warm months of the year, respectively. There were no significant associations
between IQR increase in the two-day cumulative average up to the six-day
cumulative average of the daily mean temperature and AMI during the entire year,
and warm or cold months of the year. CONCLUSION: An increase in temperature would
increase the rate of AMI hospitalization.
PMID- 28689212
TI - Coal Mine Dust Desquamative Chronic Interstitial Pneumonia: A Precursor of Dust
Related Diffuse Fibrosis and of Emphysema.
AB - BACKGROUND: Diseases associated with coal mine dust continue to affect coal
miners. Elucidation of initial pathological changes as a precursor of coal dust
related diffuse fibrosis and emphysema, may have a role in treatment and
prevention. OBJECTIVE: To identify the precursor of dust-related diffuse fibrosis
and emphysema. METHODS: Birefringent silica/silicate particles were counted by
standard microscope under polarized light in the alveolar macrophages and fibrous
tissue in 25 consecutive autopsy cases of complicated coal worker's
pneumoconiosis and in 21 patients with tobacco-related respiratory bronchiolitis.
RESULTS: Coal miners had 331 birefringent particles/high power field while
smokers had 4 (p<0.001). Every coal miner had intra-alveolar macrophages with
silica/silicate particles and interstitial fibrosis ranging from minimal to
extreme. All coal miners, including those who never smoked, had emphysema.
Fibrotic septa of centrilobular emphysema contained numerous silica/silicate
particles while only a few were present in adjacent normal lung tissue. In coal
miners who smoked, tobacco-associated interstitial fibrosis was replaced by
fibrosis caused by silica/silicate particles. CONCLUSION: The presence of
silica/silicate particles and anthracotic pigment-laden macrophages inside the
alveoli with various degrees of interstitial fibrosis indicated a new disease:
coal mine dust desquamative chronic interstitial pneumonia, a precursor of both
dust-related diffuse fibrosis and emphysema. In studied coal miners, fibrosis
caused by smoking is insignificant in comparison with fibrosis caused by
silica/silicate particles. Counting birefringent particles in the macrophages
from bronchioalveolar lavage may help detect coal mine dust desquamative chronic
interstitial pneumonia, and may initiate early therapy and preventive measures.
PMID- 28689213
TI - Respiratory Abnormalities among Occupationally Exposed, Non-Smoking Brick Kiln
Workers from Punjab, India.
AB - BACKGROUND: Brick manufacturing industry is one of the oldest and fast-growing
industries in India that employs a large section of people. Brick kiln workers
are occupationally exposed to air pollutants. Nonetheless, only a few studies
have so far been conducted on their respiratory health. OBJECTIVE: To investigate
the extent of respiratory impairment in brick kiln workers and to correlate it
with the duration of exposure. METHODS: A cross-sectional study was conducted.
Spirometric parameters of 110 non-smoking male brick kiln workers aged 18-35
years in Patiala district, Punjab, India, were compared with an age-matched
comparison group of 90 unexposed individuals. RESULTS: Brick kiln workers showed
a significant (p<0.05) decline in forced expiratory volume in 1 second (FEV1),
forced vital capacity (FVC), forced mid-expiratory flow rate (FEF25-75%) and peak
expiratory flow rate (PEFR) compared with those of the comparison group. The
extent of deterioration in lung function of brick kiln workers was associated
with the duration of exposure. In workers with >8 years of exposure, the mean
values of FEV1 (1.92 L), FVC (2.01 L), FEF25-75% (2.19 L/s) and PEFR (4.81 L/s)
were significantly (p<0.05) lower than those recorded in workers with <8 years of
exposure in whom the values were 2.01 L, 2.68 L, 2.71 L/s, and 5.76 L/s,
respectively. CONCLUSION: There is a significant association between exposure to
workplace pollutants and lung function deterioration among brick kiln workers.
PMID- 28689214
TI - Confirmatory Factor Analysis of the Finnish Job Content Questionnaire (JCQ) in
590 Professional Musicians.
AB - BACKGROUND: Poorly functioning work environments may lead to dissatisfaction for
the employees and financial loss for the employers. The Job Content Questionnaire
(JCQ) was designed to measure social and psychological characteristics of work
environments. OBJECTIVE: To investigate the factor construct of the Finnish 14
item version of JCQ when applied to professional orchestra musicians. METHODS: In
a cross-sectional survey, the questionnaire was sent by mail to 1550 orchestra
musicians and students. 630 responses were received. Full data were available for
590 respondents (response rate 38%).The questionnaire also contained questions on
demographics, job satisfaction, health status, health behaviors, and intensity of
playing music. Confirmatory factor analysis of the 2-factor model of JCQ was
conducted. RESULTS: Of the 5 estimates, JCQ items in the "job demand" construct,
the "conflicting demands" (question 5) explained most of the total variance in
this construct (79%) demonstrating almost perfect correlation of 0.63. In the
construct of "job control," "opinions influential" (question 10) demonstrated a
perfect correlation index of 0.84 and the items "little decision freedom"
(question 14) and "allows own decisions" (question 6) showed substantial
correlations of 0.77 and 0.65. CONCLUSION: The 2-factor model of the Finnish 14
item version of JCQ proposed in this study fitted well into the observed data.
The "conflicting demands," "opinions influential," "little decision freedom," and
"allows own decisions" items demonstrated the strongest correlations with latent
factors suggesting that in a population similar to the studied one, especially
these items should be taken into account when observed in the response of a
population.
PMID- 28689215
TI - Evaluation of Occupational Exposure to Nitrosamine, Carbon Black and Dust in
Rubber Processing Industry.
PMID- 28689216
TI - Concentration of Alpha Fetoprotein and Betaeta-Human Chorionic Gonadotropin Tumor
Markers in Sulfur Mustard-Exposed Veterans.
PMID- 28689217
TI - "Predatory Journals" or "Predatory Scholars?" The Essential Role of the Peer
Review Process.
PMID- 28689218
TI - Allergic inflammation is exacerbated by allergen-induced type 2 innate lymphoid
cells in a murine model of allergic rhinitis.
AB - BACKGROUND: Group 2 innate lymphoid cells (ILC2s) represent a new innate effector
leukocyte population that mediates type-2 immune response. However, the
contribution of ILC2s to allergic rhinitis (AR) is currently not well defined.
OBJECTIVE: To evaluate the potential existence and function of allergen-induced
ILC2s in the experimental AR. METHODS: We established a murine model of AR using
ovalbumin (OVA) and aluminium hydroxide. The OVA-induced ILC2s were sorted and
purified from the mouse nasal-associated lymphoid tissue (NALT). Then, we
assessed ILC2s responses to mouse recombinant interleukin (rmIL)-25, anti-IL17RB
antibody and CC chemokine ligand (CCL) 25 in the culture. After that, we
adoptively transferred the NALT-derived ILC2s alone or plus rmIL-25 or anti
IL17RB antibody to the murine model of AR to investigate their role in the nasal
allergic inflammation. RESULTS: We showed that ILC2s could be induced by OVA in
the NALT of AR model. They were induced to secrete IL-5 and IL-13 by rmIL-25, and
blocking of IL17RB contributed to the decreased production of these cytokines in
the culture. We found that CCL25 induced the NALT-derived ILC2s migration through
CC chemokine receptor 9 on ILC2s in vitro. Numbers of sneezing and nasal rubbing
as well as counts of invasive eosinophils were all enhanced after the adoptive
transfer of cultured ILC2s in vitro. The expressions of IL-5, IL-13, IL-25 and
CCL25 in the NLF of allergic mice were also increased. CONCLUSION: These findings
show that ILC2s play a proinflammatory role in the murine AR model, and also
highlight ILC2s as a new target in the future AR therapy.
PMID- 28689219
TI - Accelerating smooth molecular surface calculation.
AB - This study proposes a novel approach, namely, skin flow complex algorithm (SFCA),
to decompose the molecular skin surface into topological disks. The main
contributions of SFCA include providing a simple decomposition and fast
calculation of the molecular skin surface. Unlike most existing works which
partition the molecular skin surface into sphere and hyperboloid patches, SFCA
partitions the molecular skin surface into triangular quadratic patches and
rectangular quadratic patches. Each quadratic patch is proven to be a topological
disk and rendered by a rational Bezier patch. The skin surface is constructed by
assembling all rational Bezier patches. Experimental results show that the SFCA
is more efficient than most existing algorithms, and produces a triangulation of
molecular skin surface which is decomposable, deformable, smooth, watertight and
feature-preserved.
PMID- 28689220
TI - Morphological evaluation of median nerve: why ultrasound?
PMID- 28689221
TI - Variable refocusing flip angle single-shot fast spin echo imaging of liver
lesions: increased speed and lesion contrast.
AB - PURPOSE: To evaluate acquisition time and clinical image quality of a variable
refocusing flip angle (vrf) single-shot fast spin echo (SSFSE) sequence in
comparison with a conventional SSFSE sequence for imaging of liver lesions in
patients undergoing whole-body PET/MRI for oncologic staging. METHODS: A vrfSSFSE
sequence was acquired in 43 patients with known pancreatic neuroendocrine tumors
undergoing 68Ga-DOTA-TOC PET on a simultaneous time-of-flight 3.0T PET/MRI. Liver
lesions >=1.5 cm with radionucleotide uptake were analyzed. Contrast-to-noise
ratios (CNRs) were measured, and four blinded radiologists assessed overall image
quality. Differences in repetition time and CNR were assessed using a paired
Student's t test with p < 0.05 considered statistically significant. Inter-reader
variability was assessed with Fleiss' kappa statistic. RESULTS: 53 eligible
lesions in 27 patients were included for analysis. vrfSSFSE demonstrated higher
mean lesion CNR compared to SSFSE (9.9 +/- 4.1 vs. 6.7 +/- 4.1, p < 0.001). Mean
repetition time (TR) was 679 +/- 97 ms for the vrfSSFSE sequence compared to 1139
+/- 106 ms for SSFSE (p < 0.0001), corresponding to a 1.7-fold decrease in
acquisition time. Overall quality of liver lesion and common bile duct images
with the vrfSSFSE sequence was graded as superior than or equivalent to the SSFSE
sequence for 59% and 67% of patients, respectively. CONCLUSIONS: Compared to
conventional SSFSE, vrfSSFSE resulted in improved lesion contrast on simultaneous
PET/MRI in patients with liver metastases. Due to decreased SAR demands, vrfSSFSE
significantly decreased TR, allowing coverage of the entire liver in a single
twenty-second breath hold. This may have important clinical implications in the
setting of PET/MRI, where scan time is limited by the necessity of whole-body
image acquisition in addition to bed specific imaging.
PMID- 28689222
TI - Insights into autofluorescence patterns in Stargardt macular dystrophy using
ultra-wide-field imaging.
AB - PURPOSE: To characterize autofluorescence (AF) patterns occurring in Stargardt
macular dystrophy (STGD1) using ultra-wide-field (UWF) imaging. METHODS: This
paper is a cross-sectional observational study of 22 eyes of 11 patients (mean
age 23.44 years) with Stargardt disease-fundus flavimaculatus who presented with
decrease of vision at a tertiary eye care center. UWF short-wave AF images were
obtained from all the patients using an Optos TX200 instrument. The main outcome
measures were to assess patterns of AF changes seen on UWF AF imaging. RESULTS:
All eyes showed a central area of hypoautofluorescence at the macula along with
retinal flecks extending centrifugally as well as to the nasal side of the optic
disc. Peripapillary sparing was seen in 100% of the eyes. Flecks were seen to be
hypoautofluorescent in the center and hyperautofluorescent in the periphery in
77.8% eyes and were only hyperfluorescent in 27.2%. A background-increased
fluorescence was visible in 100% of eyes, the outer boundary of which was marked
by distribution of flecks in 81.9% eyes. A characteristic inferonasal vertical
line was seen separating the nasal hypoautofluorescent area from the temporal
hyperautofluorescent area in all the eyes. CONCLUSIONS: UWF AF changes in STGD1
are not limited to the posterior pole and may extend more peripherally. UWF
imaging is a useful tool for the assessment of patients with Stargardt macular
dystrophy.
PMID- 28689223
TI - Author response: OCT angiography in idiopathic macular hole, some methodological
concerns.
PMID- 28689224
TI - Mixed papillary-sarcomatoid carcinoma of the penis: report of an aggressive
subtype.
AB - Several different histological subtypes of penile carcinoma had been described in
the last decades, many with different biological behavior and prognosis. The
association of two histological subtypes (mixed tumors) can be observed in one
third of the cases. The most common association is of warty and basaloid tumors,
two HPV-related carcinomas. Here, we described a mixed papillary-sarcomatoid
carcinoma, never reported before. Although it is a clinical aspect of a low-grade
verruciform tumor, its prognosis showed it to be very aggressive due to the
sarcomatoid component hidden above the papillary component. The two components
showed opposite cadherin/vimentin expression pointed to epithelial-mesenchymal
transition between them.
PMID- 28689225
TI - Use of cell phones and brain tumors: a true association?
PMID- 28689226
TI - Forewing structure of the solitary bee Osmia bicornis developing on heavy metal
pollution gradient.
AB - Wild bees in natural conditions can develop under various environmental
stressors. Heavy metal pollution of the environment is one of the most widely
studied stressors in insects, yet its effect is poorly described in bees. We have
measured how pollution of the environment along a zinc, cadmium and lead
contamination gradient in Poland affects bee development, using red mason bees
(Osmia bicornis) as a model and their forewing asymmetry measures to assess
possible developmental instabilities. We have also described wing asymmetry
measures in the red mason bee-an important managed pollinator species-for the
first time. The development of bee larvae in a contaminated environment did not
affect forewing asymmetry measures, but it did lead to a negative correlation of
wing size with contamination in females. Bees also showed a clear change in their
asymmetry measures between various seasons, suggesting other, unknown
environmental factors affecting wing asymmetry more than pollution. Sexes were
found to have different forewing shape and size, larger females having larger
forewings than the smaller males. The direction of size asymmetry was in favour
of the left side in both sexes and also shape differences between the left and
right wings showed similar tendencies in males and females. The levels of
forewing shape and size asymmetry were smaller in females, making them the more
symmetrical sex.
PMID- 28689227
TI - Opposite domination of cyclic and pseudocyclic electron flows in short
illuminated dark-adapted leaves of angiosperms and gymnosperms.
AB - The present work was aimed to explain the recently reported higher O2-dependent
electron flow capacity in gymnosperms than in angiosperms and to search for other
differences in the electron transport processes by simultaneous characterization
of the relative capacities of pseudocyclic (direct or Flavodiiron proteins (Flv)
mediated O2-reduction, Mehler(-like) reactions) and cyclic electron flows around
photosystem I (CEF-PSI). To this end, a comparative multicomponent analysis was
performed on the fluorescence decay curves of dark-adapted leaves after
illumination with a 1-s saturating light pulse. In both gymnosperms and
angiosperms, two or three exponential decay components were resolved: fast (t
1/21 ~ 170-260 ms), middle (~1.0-2.3 s), and slow (>4.2 s). The sensitivity of
the decay parameters (amplitudes A1-3, halftimes t 1/2 1-3) to the alternative
electron flows was assessed using Arabidopsis pgr5 and ndhM mutants, defective in
CEF-PSI, Synechocystis sp. PCC 6803 Deltaflv1 mutant, defective in Flv-mediated
O2-photoreduction, different O2 concentrations, and methyl viologen treatment. A1
reflected the part of electrons involved in linear and O2-photoreduction pathways
after PSI. The middle component appeared in pgr5 (but not in ndhM), in
gymnosperms under low O2, and in Deltaflv1, and reflected limitations at the PSI
acceptor side. The slow component was sensitive to CEF-PSI. The comparison of
decay parameters provided evidence that Flv mediate O2-photoreduction in
gymnosperms, which explains their higher O2-dependent electron flow capacity. The
concomitant quantification of relative electrons branching in O2-photoreduction
and CEF-PSI pathways under the applied non-steady-state photosynthetic conditions
reveals that CEF-PSI capacity significantly exceeds that of O2-photoreduction in
angiosperms while the opposite occurs in gymnosperms.
PMID- 28689228
TI - Impact of a rapid molecular test for positive blood cultures from neonatal
intensive care patients on clinical management: a retrospective audit.
AB - BACKGROUND: Both Staphylococcus aureus and coagulase negative Staphylococci are
common causes of late-onset neonatal sepsis in the neonatal intensive care unit
(NICU), usually relating to intravascular access device infections. AIMS: This
project aimed to review the impact on antimicrobial treatment and clinical
outcome in the NICU setting, of the introduction of the Xpert MRSA/SA BC test
(Cepheid, USA) for the identification of staphylococci in blood cultures.
METHODS: A retrospective audit was carried out of the pre- and post-intervention
periods; the intervention was the introduction of the Xpert MRSA/SA BC test.
RESULTS: In total, 88 neonates had positive blood cultures with Staphylococcus
spp., comprising 42 neonates in the pre-intervention and 46 in the post
intervention groups. The pre-intervention group had a higher birth weight (1.541
kg vs. 1.219 kg, p = 0.05) and higher platelet count (288 vs. 224 * 109/L, p =
0.05). There was a trend towards a shorter duration of antimicrobial therapy in
term infants and in the length of admission; however, this was not statistically
significant (p = 0.2). All of the nine infants post-intervention with significant
bacteraemia (S. aureus =3, CoNS =6) were changed to the optimal antimicrobial at
the time the result was available. CONCLUSIONS: This study shows that the
introduction of the Xpert MRSA/SA BC test can lead to a reduction in the length
of admission and duration of antimicrobials in term infants; however, the
difference was not statistically significant. All nine infants with clinically
significant bacteraemia were treated with the appropriate antimicrobial when the
Xpert MRSA/SA BC test result was available.
PMID- 28689229
TI - Detection of candidate nectin gene mutations in infertile men with severe
teratospermia.
AB - PURPOSE: Approximately 40% of infertile men have an abnormal semen analysis,
resulting from either abnormalities of sperm production (defective
spermatogenesis) or sperm shape (defective spermiogenesis). This latter process
is dependent upon the function of Sertoli cells, which maintain specialized
junctional complexes with germ cells. Nectins, members of the immunoglobulin
superfamily, participate in formation of these dynamic complexes. Male mice in
which the nectin-2 or nectin-3 gene is knocked out are sterile. Their spermatozoa
exhibit severe teratospermia, altered motility, and an impaired ability to
fertilize eggs. We asked whether mutations in the protein coding regions of the
nectin-2 (aka PVRL2) and nectin-3 (aka PVRL3) genes could be detected in men from
infertile couples whose semen analysis revealed unimpaired sperm production,
judged by normal sperm concentration, but severe abnormalities in sperm shape.
METHODS: Ejaculates were snap frozen in liquid nitrogen and later submitted for
Sanger analysis of these two genes, to detect mutations in their protein coding
regions. RESULTS: Eighty-nine of 455 ejaculates (19.5%) met the inclusion
criteria for study. Two of the 56 samples that were successfully analyzed for
nectin-2 (3.6%) and one of 73 (1.3%) analyzed for nectin-3 possessed possibly
damaging mutations. CONCLUSIONS: Despite the small-scale nature of the study, at
least two low-frequency deleterious variants were identified. These results
suggest the need for a larger-scale study of sequence variants in the nectins in
severe teratospermia.
PMID- 28689230
TI - The extended, transnasal, transsphenoidal approach for anterior skull base
meningioma: considerations in patient selection.
AB - PURPOSE: In this study, we set out to define our institutional criteria for
patient eligibility for transsphenoidal resection of parasellar meningiomas, and
to report our experience with extended transnasal approaches for these lesions.
We aimed to discuss the important considerations of patient selection and risk
stratification to optimize outcomes for patients with these difficult lesions,
and also include considerations that should be reviewed during surgical approach
selection. METHODS: Medical records from Brigham and Women's Hospital were
retrospectively reviewed for all patients who underwent transsphenoidal surgery
for pituitary disease with the senior author from April 2008 to March 2017 (938
procedures). Patients undergoing surgery for anterior skull base meningioma were
identified and patient data were collected. RESULTS: Seven patients (four women,
three men) underwent transsphenoidal resection (five endoscopic, one microscopic,
and one hybrid endoscopic/microscopic) of pathologically-confirmed anterior skull
base meningiomas during the study period. Five patients presented with visual
field deficits, three presented with headache, two presented with
hypopituitarism, and one woman presented with infertility. The median maximum
tumor diameter was 1.7 cm (range 1.4-4.2 cm). Six patients underwent subtotal
resection, and one underwent gross total resection. The median MIB-1 index was
2.3 (range 1.0-7.6). Complications included two readmissions (one on POD11 for
small bowel obstruction, one on POD48 for epistaxis), and the development of new
onset thyroid deficiency and transient diabetes insipidus in one patient. Two
patients had reoperations by craniotomy for tumor recurrence after 5 and 6 years,
respectively. CONCLUSIONS: Although more commonly treated transcranially,
anterior skull base meningiomas are sometimes amenable to resection
transphenoidally. Patient selection is critical, and multiple factors, including
tumor size, consistency, and location, patient and surgeon preference, and
presenting symptoms each affect the optimum surgical approach. We have developed
criteria for patient selection so that transsphenoidal surgery can be used to
resect or debulk anterior skull base meningiomas safely and with favorable
outcomes.
PMID- 28689232
TI - Co-circulation of three clusters of 793/B-like avian infectious bronchitis virus
genotypes in Iranian chicken flocks.
AB - Avian infectious bronchitis (IB) is an acute and highly contagious viral disease
causing severe economic losses in the poultry industry. The 793/B IB virus is an
important infectious bronchitis virus (IBV) genotype currently circulating in
several countries, including Iran. One hundred confirmed IBV samples (between
2014 and 2015; from 15 provinces in Iran) were selected for genotyping based on
S1 sequencing. After phylogenetic analysis, it was found that 30% of the IBV
isolates belonged to the 793/B genotype. Results showed that the Iranian 793/B
like IBV isolates could be divided in to three clusters: 4/91-like (50%), 1/96
like (40%), and IB88-like (10%). The sequence similarity between Iranian 793/B
like IBV isolates is 87.69%-100%. The highest identity is between the 4/91 and
IB88 clusters (96.38%), and the lowest similarity is between the 1/96 and IB88
clusters (87.62%). This study provides a comprehensive analysis of 793/B-type IBV
in Iran and characterization of IBV molecular epidemiology in the country.
PMID- 28689231
TI - Barriers to exercise for patients with renal disease: an integrative review.
AB - Renal disease is a common health condition that leads to loss of physical
function, frailty, and premature loss of independence in addition to other severe
comorbidities and increased mortality. Increased levels of physical activity and
initiation of exercise training is recommended in the current guidelines for all
patients with renal disease, but participation and adherence rates are low. The
barriers to exercise and physical activity in patients with renal disease are not
well defined and currently based on patient provider perception and opinion.
There have been no published reviews that have synthesized published findings on
patient reported barriers to exercise. This integrative literature review
therefore aimed to identify the current understanding of patient reported
barriers to regular exercise. This integrative review found that patient
perceived barriers to exercise are not consistent with the barriers that have
been identified by renal disease specialists and healthcare providers, which were
disinterest, lack of motivation, and being incapable of exercise. The patient
reported barriers identified through this review were complex and diverse, and
the most frequently reported patient perceived barrier to exercise was low energy
levels and fatigue. It is clear that additional research to identify patient
perceived barriers to exercise is needed and that patient directed interventions
to address these barriers should be developed. This integrative review provides
information to the interdisciplinary nephrology team that can be used to tailor
their assessment of barriers to exercise and provide exercise education for
patients with renal disease.
PMID- 28689233
TI - Detection and genotyping of bovine leukemia virus in Mexican cattle.
AB - Bovine leukemia virus (BLV) was detected and genotyped in a population of 201
dairy cattle from central Mexico. Using a commercial indirect enzyme-linked
immunosorbent assay (iELISA) kit, 118 polymerase chain reaction (PCR)-positive
and BLV antibody-positive samples were identified; the concordance between tests
was substantial. A phylogenetic study of 27 partial sequences of the env gene
gp30 was performed. Four mutations were detected involving the PXXP motif in the
cytoplasmic domain of the transmembrane protein. This study provided evidence of
the efficacy of PCR for the detection of BLV and demonstrated the presence of
genotype 1 BLV in Mexico.
PMID- 28689234
TI - Evolutionary insights into the fusion protein of Newcastle disease virus isolated
from vaccinated chickens in 2016 in Egypt.
AB - Newcastle disease virus (NDV) infections are one of the most devastating causes
of economic losses in the poultry industry and despite extensive vaccination,
outbreaks are being reported around the globe especially from developing and
tropical countries. Analysis of NDV field strains from vaccinated flocks would
highlight essential areas of consideration not only to design effective
immunization strategies but also to devise vaccines that provide sterile
immunity. For this purpose, 91 NDV suspected outbreaks were investigated and
screened for NDV genetic material. A total of 16 NDV-positive isolates were
examined using biological, genetics and bioinformatics analysis to assess the
epidemiological association and to identify motifs that are under vaccine-induced
immune pressures. In line with the clinical outcomes, all isolates showed the
112RRQKR|F117 cleavage motif and phylogenetic analysis revealed grouping of
isolates into the genotype VII, and specifically sub-genotype VIId. Further
analysis of the putative fusion protein sequence showed a number of substitutions
(n=10) in functionally important domains and based on these differences, the
studied isolates could be categorized into four distinct groups (A-D).
Importantly, two residues (N30 and K71) were conserved in the commercial live
vaccine and Egyptian field strains that are present in class II, genotype II.
Collectively, these data enhance our knowledge of the evolution of genotype VIId
NDV under the vaccine-induced immune pressures. In addition, our findings suggest
that the use of genotype II-type vaccines in Egypt may be implicated in the
emergence of new variants rather than providing benefits against NDV infections.
PMID- 28689236
TI - Etiological classification of ischemic stroke in young patients: a comparative
study of TOAST, CCS, and ASCO.
AB - Analysis of stroke subtypes is important for making treatment decisions and
prognostic evaluations. The TOAST classification system is most commonly used,
but the CCS and ASCO classification systems might be more useful to identify
stroke etiologies in young patients whose strokes have a wide range of different
causes. In this manuscript, we aim to compare the differences in subtype
classification between TOAST, CCS, and ASCO in young stroke patients. The TOAST,
CCS, and ASCO classification schemes were applied to 151 patients with ischemic
stroke aged 18-49 years old and the proportion of subtypes classified by each
scheme was compared. For comparison, determined etiologies were defined as cases
with evident and probable subtypes when using the CCS scheme and cases with grade
1 and 2 subtypes but no other grade 1 subtype when using the ASCO scheme. The
McNemar test with Bonferroni correction was used to assess significance. By
TOAST, 41.1% of patients' stroke etiology was classified as undetermined
etiology, 19.2% as cardioembolic, 13.2% as large artery atherosclerosis, 11.3% as
small vessel occlusion, and 15.2% as other causes. Compared with TOAST, both CCS
and ASCO assigned fewer patients to the undetermined etiology group (30.5% p <
0.001 and 26.5% p < 0.001, respectively) and assigned more patients to the small
vessel occlusion category (19.9%, p < 0.001, and 21.9%, p < 0.001, respectively).
Additionally, both schemes assigned more patients to the large artery
atherosclerosis group (15.9 and 16.6%, respectively). The proportion of patients
assigned to either the cardioembolic or the other causes etiology did not differ
significantly between the three schemes. Application of the CCS and ASCO
classification schemes in young stroke patients seems feasible, and using both
schemes may result in fewer patients being classified as undetermined etiology.
New studies with more patients and a prospective design are needed to explore
this topic further.
PMID- 28689235
TI - QSAR modeling and in silico design of small-molecule inhibitors targeting the
interaction between E3 ligase VHL and HIF-1alpha.
AB - Protein-protein interactions (PPIs) have attracted much attention recently
because of their preponderant role in most biological processes. The prevention
of the interaction between E3 ligase VHL and HIF-1[Formula: see text] may improve
tolerance to hypoxia and ameliorate the prognosis of many diseases. To obtain
novel potent inhibitors of VHL/HIF-1[Formula: see text] interaction, a series of
hydroxyproline-based inhibitors were investigated for structural optimization
using a combination of QSAR modeling and molecular docking. Here, 2D- and 3D-QSAR
models were developed by genetic function approximation (GFA) and comparative
molecular field analysis (CoMFA) and comparative molecular similarity index
analysis (CoMSIA) methods, respectively. The top-ranked models with strict
validation revealed satisfactory statistical parameters (CoMFA with [Formula: see
text], 0.637; [Formula: see text], 0.955; [Formula: see text], 0.944; CoMSIA with
[Formula: see text], 0.649; [Formula: see text], 0.954; [Formula: see text],
0.911; GFA with [Formula: see text], 0.721; [Formula: see text], 0.801; [Formula:
see text], 0.861). The selected five 2D-QSAR descriptors were in good accordance
with the 3D-QSAR results, and contour maps gave the visualization of feature
requirements for inhibitory activity. A new diverse molecular database was
created by molecular fragment replacement and BREED techniques for subsequent
virtual screening. Eventually, 31 novel hydroxyproline derivatives stood out as
potential VHL/HIF-1[Formula: see text] inhibitors with favorable predictions by
the CoMFA, CoMSIA and GFA models. The reliability of this protocol suggests that
it could also be applied to the exploration of lead optimization of other PPI
targets.
PMID- 28689237
TI - Effects of Different Sources and Levels of Zinc on Growth Performance, Nutrient
Digestibility, and Fur Quality of Growing-Furring Male Mink (Mustela vison).
AB - The objective of this study was to investigate the effects of different sources
and levels of zinc (Zn) on growth performance, nutrient digestibility, serum
biochemical parameters, and fur quality in growing-furring male mink. Animals in
the control group were fed a basal diet with no Zn supplementation. Mink in the
other nine treatments were fed the basal diet supplemented with Zn from either
grade Zn sulfate (ZnSO4.7H2O), Zn glycinate (ZnGly), or Zn pectin
oligosaccharides (ZnPOS) at concentrations of either 100, 300, or 900 mg Zn/kg
dry matter. One hundred and fifty healthy 15-week-old male mink were randomly
allocated to ten dietary treatments (n = 15/group) for a 60-day trial from mid
September to pelting in December. Mink in the Zn-POS groups had higher average
daily gain than those in the control group (P < 0.05). Zn source slightly
improved the feed/gain (P = 0.097). N retention was increased by Zn addition (P <
0.05). Mink supplemented with dietary Zn had higher (P < 0.05) pancreas Zn level
than the control group. Fur length was greater (P < 0.05) in ZnGly and ZnPOS
groups compared with the control. In addition, fur length and fur density
increased (linear, P < 0.05) with Zn supplementation in the diet. In conclusion,
our data show that dietary Zn addition improves growth performance by increasing
nitrogen retention and fat digestibility in growing-furring mink and Z-POS is
equally bioavailable to mink compared to ZnGly.
PMID- 28689238
TI - Transobturator midurethral sling: What should patients expect after surgery?
AB - INTRODUCTION AND HYPOTHESIS: Midurethral sling (MUS) surgeries are minimally
invasive procedures; however, they are not free of postoperative complications.
The aim of the study was to assess the occurrence of lower urinary tract symptoms
(LUTS) (urgency, nocturia, frequency, splitting/spraying, hesitancy, terminal
dribbling, and subjective feeling of postvoid residual) in patients suffering
from stress (SUI) or mixed (MUI) urinary incontinence with a predominant SUI
component before and after transobturator MUS placement. METHODS: The study group
consisted of 88 women with SUI and 18 with MUI who underwent transobturator MUS.
All participants were questioned with a self-developed questionnaire before and
after surgery regarding the presence of LUTS. RESULTS: Seven days after surgery,
62 patients (58.5%) noted voiding and postmicturition symptoms, whereas 67
(63.2%) reported problems in storage. The more commonly reported LUTS at week 1
after surgery were urgency (52.8%), splitting/spraying (41.5%), and feeling of
incomplete bladder emptying (34.0%). Patients perceived that splitting/spraying
was the most bothersome. After 6 months, the most common LUTS reported were
hesitancy (14.1%), terminal dribbling (10.4%), and splitting/spraying (9.4%). We
noticed a decrease in the number of urgency episodes >2.7 times (p < 0.001)
compared with baseline. After 6 months, 97 (91.5%) patients reported the lack of
incontinence episodes. CONCLUSIONS: A vast majority of patients after MUS suffer
from LUTS in the early postoperative period; however, the majority of undesired
symptoms resolve spontaneously within the first 6 months postsurgery.
PMID- 28689239
TI - Structure-function relationship of the human external anal sphincter.
AB - INTRODUCTION AND HYPOTHESIS: Obstetrical external anal sphincter (EAS) injury and
subsequent dysfunction are leading risk factors for female fecal incontinence
(FI). Limited knowledge of the EAS structure-function relationship hinders
treatment optimization. We directly measured functionally relevant intrinsic
parameters of human EAS and tested whether vaginal delivery alters the EAS
structure-function relationship. METHODS: Major predictors of in vivo EAS
function were compared between specimens procured from vaginally nulliparous (VN,
n = 5) and vaginally parous (VP, n = 7) cadaveric donors: operational sarcomere
length (Ls), which dictates force-length relationship; physiological cross
sectional area (PCSA), which determines isometric force-generating capacity;
fiber length (Lfn), responsible for muscle excursion and contractile velocity;
and muscle stiffness. Data were analyzed using unpaired and paired t tests, alpha
< 0.05. Results are presented as mean +/- SEM. RESULTS: The VN and VP (median
parity 3) groups were similar in age and BMI. No gross anatomical defects were
identified. EAS Ls (2.36 +/- 0.05 MUm) was shorter than the optimal Lso (2.7
MUm), at which contractile force is maximal, P = 0.0001. Stiffness was lower at
Ls than Lso (5.4 +/- 14 kPa/MUm vs 35.3 +/- 12 kPa/MUm, P < 0.0001). This
structural design allows active and passive tension to increase with EAS
stretching. EAS relatively long Lfn (106 +/- 24.8 mm) permits rapid contraction
without decreased force, whereas intermediate PCSA (1.3 +/- 0.3 cm2) is conducive
to maintaining resting tone. All parameters were similar between groups.
CONCLUSIONS: This first direct examination of human EAS underscores how EAS
intrinsic design matches its intended function. Knowledge of the EAS structure
function relationship is important for understanding the pathogenesis of FI and
the optimization of treatments for EAS dysfunction.
PMID- 28689240
TI - suPAR and chronic kidney disease-a podocyte story.
AB - The soluble urokinase-type plasminogen activator receptor (suPAR) is a
circulating signaling molecule derived from immature myeloid cells. Elevated
levels of suPAR have been linked to the pathogenesis of the kidney disease focal
and segmental glomerulosclerosis. Here, suPAR acts on podocytes by activating
alphavbeta3 integrins. Large observational studies showed that suPAR also
predicts chronic kidney disease incidence and progression by predating the
disease by several years prior to any other known marker of renal dysfunction.
suPAR is rapidly developing into a prime target for pharmacotherapy as its
neutralization is forecasted to be feasible and safe.
PMID- 28689241
TI - Putative role of an SLC45 H+/sugar cotransporter in mammalian spermatozoa.
AB - In the present study, we describe the detection and analysis of a novel type of
sugar transporter in mammalian spermatozoa. This transporter belongs to the SLC45
family for which two features are remarkable and distinguish it from other known
families of sugar transporters. Firstly, SLC45 transporters recognise not only
the monosaccharides glucose or fructose but also the disaccharide sucrose as a
substrate. Secondly, the uptake of sugars is coupled to a proton gradient. Uptake
experiments using radioactively labelled sucrose indicated a functional
transporter of the SLC45 family in bull spermatozoa. Real-time PCR as well as
Western blots demonstrated the occurrence of the SLC45 member A4 in mouse testis
and sperms. Furthermore, immunocytochemical analysis of mouse tissues revealed
that the signal of SLC45A4 was mainly located in the principle piece of
spermatozoa. We postulate that the SLC45A4 transporter plays an important role in
nutrition of spermatozoa during their maturation in the epididymis. Moreover, we
suggest that knowledge about the presence of the SLC45A4 may be useful also for
the methodical improvement of cryopreservation of mammalian spermatozoa.
PMID- 28689242
TI - Capsular bag irrigation using 0.025% povidone-iodine in balanced salt solution
PLUS for the treatment of postoperative endophthalmitis.
AB - We examined the effectiveness and adverse events of using balanced salt solution
(BSS) PLUS containing 0.025% povidone-iodine, a non-oculotoxic concentration, for
capsular bag irrigation in a case of endophthalmitis mainly involving the
anterior chamber. A 57-year-old female underwent cataract surgery and developed
hypopyon on day 3 after surgery, with mainly anterior chamber inflammation. The
capsular bag was irrigated with BSS PLUS containing 0.025% povidone-iodine. Gram
negative rods were detected from the anterior chamber fluid. Post-procedural
visual acuity was 24/20. In a case, endophthalmitis was resolved and there were
no adverse events. With the recent increase in multidrug-resistant bacteria, use
of 0.025% povidone-iodine in BSS PLUS for anterior chamber irrigation is expected
to be useful.
PMID- 28689243
TI - Giant intrastromal cleft in corneal hydrops.
AB - A 15-year-old male patient with corneal hydrops and a giant intrastromal cleft
(pseudocyst) successfully received medical treatment with topical prednisolone,
hypertonic saline solution and ocular hypotensive eyedrops. Anterior segment
optical coherence tomography (OCT) was used as an auxiliary tool for assessing
the response to treatment during follow-up time (33 months).
PMID- 28689244
TI - Changes in Management of Poorly Compliant Bladder in Botulinum Toxin A Era.
AB - Bladder compliance is a measure of distensibility. Maladies such as
myelodysplasia, myelomeningocele, spinal cord injury, multiple sclerosis and
obstructive uropathy are known to decrease bladder compliance. Decrease in
bladder compliance is a characteristic of neurogenic bladders. The
pathophysiology of bladder compliance is complex but ultimately leads to high
pressure during filling and storage phases. These high pressures lead to renal
impairment, incontinence, and recurrent urinary tract infections. This review
presents management of poorly compliant bladders with onabotulinumtoxinA.
PMID- 28689245
TI - Imaging of renal medullary carcinoma in children and young adults: a report from
the Children's Oncology Group.
AB - BACKGROUND: Renal medullary carcinoma is a rare renal malignancy of childhood.
There are no large series describing the imaging appearance of renal medullary
carcinoma in children. OBJECTIVE: To characterize the clinical and imaging
features of pediatric renal medullary carcinoma at initial presentation.
MATERIALS AND METHODS: We retrospectively analyzed images of 25 pediatric
patients with renal medullary carcinoma enrolled in the Children's Oncology Group
renal tumors classification, biology and banking study (AREN03B2) from March 2006
to August 2016. Imaging findings of the primary mass, and patterns of
locoregional and distant spread were evaluated in correlation with pathological
and surgical findings. RESULTS: Median age at presentation was 13 years (range: 6
21 years), with a male predominance (3.2:1). The overall stage of disease at
initial presentation was stage 1 in 1, stage 2 in 2 and stage 4 in 22. Maximum
diameter of the primary renal mass ranged from 1.6 to 10.3 cm (mean: 6.6 cm) with
a slight right side predilection (1.5:1). Enlarged (>1 cm short axis)
retroperitoneal lymph nodes were identified at initial staging in 20/25 (80%)
cases, 10 of which were histologically confirmed while the others did not undergo
surgical sampling. Enlarged lymph nodes were also identified in the mediastinum
(14/25; 56%) and supraclavicular regions (4/25; 16%). Metastatic disease was
present in the lungs in 19/25 (76%) and liver in 6/25 (24%). The pattern of lung
metastases was pulmonary lymphangitic carcinomatosis: 10 cases (9 bilateral, 1
unilateral), pulmonary nodules with indistinct margins: 6 cases, pulmonary
nodules with distinct margins: 2 cases, while 1 case had pulmonary nodules with
both indistinct and distinct margins. Pulmonary lymphangitic carcinomatosis was
pathologically confirmed in 4/10 cases. All cases with pulmonary lymphangitic
carcinomatosis had associated enlarged mediastinal lymph nodes. CONCLUSION: Renal
medullary carcinoma in children and young adults presents at an advanced local
and distant stage in the majority of patients. The diagnosis of renal medullary
carcinoma should be considered when a child or young adult presents with a poorly
defined/infiltrative, centrally located renal mass, especially in the setting of
known sickle cell hemoglobinopathy. Distant metastases are common at initial
presentation in the lungs, distant lymph nodes and liver and often involve
multiple sites simultaneously. Pulmonary lymphangitic carcinomatosis, a
distinctive and uncommon form of lung metastasis in children, is common in this
patient population.
PMID- 28689246
TI - Parasites and asthma.
AB - Nowadays, many studies have found low morbidity of asthma in epidemic areas of
parasitic diseases, as shown by the hygiene hypothesis. It is obvious that some
parasite infections can prevent asthma and studies have been carried out to
clarify the mechanism of the preventive effect and search for the future
asthmatic therapies. Previous findings have indicated that this mechanism may be
related to the immune response switching from Th1 to Th2 and important cells
induced by parasites, including the regulatory T cells, regulatory B cells,
dendrite cells, and alternatively activated macrophages. Cytokine IL-10 also
plays a nonredundant role in protection against allergic airway inflammation in
asthma. This review focuses on the relationship between parasites and asthma, and
the potential protection mechanism involved.
PMID- 28689247
TI - Loop-mediated isothermal amplification as a reliable assay for Toxocara canis
infection in pet dogs.
AB - Keeping of infected dogs as pet results in the potential transmission risk
factors for shedding helminthic infections such as toxocariasis. Lack of accurate
identification of Toxocara canis eggs in non-dewormed infected pet dogs remains a
diagnostic concern among researchers. In this study, dog owners were asked to
fill up a questionnaire regarding their pets and their attitude towards the
deworming regimen. One hundred faecal samples were collected from pet dogs
(Northwest Iran) and were subsequently identified by the ZnSo4 flotation
technique, PCR and loop-mediated isothermal amplification (LAMP) assays. The DNA
of the recovered T. canis eggs was then extracted and amplified by LAMP and PCR.
Furthermore, ITS2 amplicons were sequenced for appraisal of the phylogenetic
analysis. Nine, 5 and 11% of T. canis infections were identified by microscopy,
PCR and LAMP, respectively. It was detected that LAMP was 10 times (10-10to 10-13
g/MUl) more sensitive than PCR (10-10to 10-12 g/MUl). The kappa value between
LAMP and PCR indicated a faint concurrence (0.463). The kappa coefficient between
LAMP and flotation technique indicated a strong agreement (0.667). The highest
infection rate (n = 11) was detected in non-dewormed pet dogs, particularly those
less than 3 months old (P < 0.05). None of the infected dogs had a history of
walking and kennelled behaviours in public places. The LAMP assay can address as
a simple, rapid and highly sensitive technique for detecting low burden of T.
canis eggs in infected pet dogs. It was proposed that the dog holder's awareness
is insufficient to implement regular deworming schedules. Additionally, regional
policymakers should broadly revise anthelmintic treatment guidelines.
PMID- 28689248
TI - Daily self-weighing and weight gain prevention: a longitudinal study of college
aged women.
AB - Daily self-weighing has been suggested as an important factor for weight loss
maintenance among samples with obesity. This study is a secondary analysis that
examined daily self-weighing in association with weight and body composition
outcomes over 2 years among young women with vulnerability for weight gain. Women
(N = 294) of varying weight status completed self-weighing frequency
questionnaires and weight was measured in the clinic at baseline, 6 months, 1,
and 2 years; DXA scans were completed at baseline, 6 months and 2 years.
Multilevel models examined the relationship between daily self-weighing (at any
point in the study) and trajectories of BMI and body fat percentage. Daily self
weighing was associated with significant declines in BMI and body fat percent
over time. Future research is needed to examine causal relations between daily
self-weighing and weight gain prevention. Nonetheless, these data extend the
possibility that daily self-weighing may be important for prevention of unwanted
weight gain.
PMID- 28689249
TI - Caregiver perspectives on the social competence of pediatric brain tumor
survivors.
AB - : ?: Pediatric brain tumor survivors are at risk for significant difficulties
related to social competence. Little research has examined factors that
contribute to survivor social problems. PURPOSE: The current study is grounded in
a model of social competence for youth with brain disorder and used qualitative
and quantitative methods to obtain caregiver perspectives on survivor social
competence and identify pertinent risk and resistance factors. METHODS: The study
occurred in two phases, including focus groups with 36 caregivers of 24 survivors
and confirmatory interviews with 12 caregivers of 12 survivors. RESULTS:
Qualitative content analyses resulted in three themes that were illustrative of
the model of social competence. Themes included (1) the impact of survivor
sequelae on social function; (2) the role of family in evaluating and promoting
survivor social development; and (3) the match between the survivor's social
context and developmental needs. Quantitative data supported the associations
between survivor social skills, survivor executive function, and family
functioning. CONCLUSIONS: Overall, findings underscore the influence of risk and
resistance factors across different systems on survivor social competence and
suggest directions for future research and intervention efforts.
PMID- 28689252
TI - Erratum to: The Validity of a New Structured Assessment of Gastrointestinal
Symptoms Scale (SAGIS) for Evaluating Symptoms in the Clinical Setting.
PMID- 28689251
TI - Genome-Wide Analysis of DNA Methylation in Hyperoxia-Exposed Newborn Rat Lung.
AB - PURPOSE: Oxygen therapy is often required to treat newborn infants with
respiratory disorders. Prolonged exposure of neonatal rats to hyperoxia reduced
alveolar septation, increased terminal air space size, and increased lung
fibrosis; these conditions are very similar to those of human bronchopulmonary
dysplasia. Epigenetic regulation of gene expression plays a crucial role in
bronchopulmonary dysplasia development. METHOD: We reared Sprague-Dawley rat pups
in either room air (RA, n = 24) or an atmosphere containing 85% O2 (n = 26) from
Postnatal Days 1 to 14. Methylated DNA immunoprecipitation (MeDIP) was used to
analyze genome-wide DNA methylation in lung tissues of neonatal rats. Hyperoxia
exposed rats exhibited larger air spaces and thinner septa than RA-exposed rats
did on Postnatal Day 14. The rats exposed to hyperoxia exhibited significantly
higher mean linear intercepts than did the rats exposed to RA. We applied MeDIP
next-generation sequencing for profiling changes in DNA methylation in the rat
lungs exposed to hyperoxia and RA. We performed bioinformatics and pathway
analyses on the raw sequencing data to identify differentially methylated
candidate genes. RESULTS: Our in vivo model revealed that neonatal hyperoxia
exposure arrested alveolarization on Postnatal Day 14. We found that the ErbB,
actin cytoskeleton, and focal adhesion signaling pathways are epigenetically
modulated by exposure to hyperoxia. We demonstrated that hyperoxia exposure
contribute in delaying lung development through an epigenetic mechanism by
disrupting the expression of genes in lungs that might be involved in
alveolarization. CONCLUSIONS: These data indicate that aberrant DNA methylation
and deregulation of the actin cytoskeleton and focal adhesion pathways of lung
tissues may be involved in the pathophysiology of hyperoxia-induced arrested
alveolarization.
PMID- 28689250
TI - Multicenter, cross-sectional observational study of the impact of neuropathic
pain on quality of life in cancer patients.
AB - PURPOSE: Neuropathic cancer pain (NCP) is a common and potentially debilitating
symptom in cancer patients. We investigated the prevalence of NCP, as well as its
management and association with QOL. METHODS: Cancer patients with pain >=1 on
the visual analogue scale (VAS) were surveyed with the Douleur Neuropathique
(DN4) questionnaire, the Brief Pain Inventory-Short Form (BPI-SF), and the
EuroQOL five dimensions (EQ-5D) questionnaire. The associations between NCP and
pain severity or NCP and QOL, while controlling for variables relevant to QOL,
were then analyzed. RESULTS: A total of 2003 patients were enrolled in this
survey; the prevalence of NCP was 36.0% (n = 722, 95% CI, 32.5-39.5). We found
that NCP in cancer patients was closely correlated to a higher pain severity (BPI
SF; 4.96 +/- 1.94 versus 4.24 +/- 2.02, p < 0.001), and in patients with NCP,
pain more severely interfered with daily living, as compared to those without NCP
(BPI-SF; 4.86 +/- 2.71 versus 4.41 +/- 2.87, p < 0.001). Patients with NCP also
had worse QOL than those without NCP, as measured by EQ-5D index score (0.47 +/-
0.30 vs. 0.51 +/- 0.30, p = 0.005), and this was confirmed using multivariate
analysis (p < 0.001), even after controlling for other variables such as age,
sex, disease stage, cancer duration, radiotherapy, chemotherapy, and
comorbidities. Importantly, adjuvant analgesics were used in less than half of
patients with NCP (n = 358, 46.4%). CONCLUSIONS: We found that NCP in cancer
patients was significantly associated with a worsened QOL, and current management
is inadequate. Therefore, future research aimed at developing improved strategies
for management of NCP is required.
PMID- 28689253
TI - Effect of arteether and pyrimethamine coadministration on the pharmacokinetic and
pharmacodynamic profile of ormeloxifene.
AB - The study was intended to investigate the effect of concomitant administration of
antimalarial drug (pyrimethamine or arteether) on pharmacokinetic and post coitus
contraceptive efficacy of ormeloxifene in female Sprague-Dawley rats. A serial
sampling technique coupled with LC-MS/MS detection was utilized for
quantification of ormeloxifene in plasma samples collected from female rats
treated with ormeloxifene only and ormeloxifene with pyrimethamine or arteether.
Coitus-proven female rats were utilized to investigate the effect of
pyrimethamine or arteether coadministration on contraceptive efficacy of
ormeloxifene by investigating the presence or absence of implantations and status
of corpora lutea on day 10 post coitum. None of the sperm-positive rats treated
with ormeloxifene with or without coadministration of pyrimethamine or arteether
showed any sign of pregnancy, confirming that concomitant administration of
antimalarial drugs (pyrimethamine or arteether) did not affect the
pharmacodynamic profile of ormeloxifene. Although there was no sign of
pharmacodynamic interaction, the volume of distribution of ormeloxifene increased
significantly on cotreatment with pyrimethamine. However, coadministration of
arteether did not affect any of the pharmacokinetic parameters of ormeloxifene.
The compiled results of preliminary study in female rats support that
pyrimethamine or arteether can be prescribed with ormeloxifene.
PMID- 28689254
TI - Desensitization of the human 5-HT4 receptor in isolated atria of transgenic mice.
AB - In the human cardiovascular system, serotonin (5-HT) exerts positive inotropic
and chronotropic effects mediated by 5-HT4 receptors. Moreover, 5-HT4 receptor
stimulation can cause arrhythmias in the human heart. Response to 5-HT can fade
due to desensitization of the receptor system and/or activation of
phosphodiesterases. In this study, we investigated a potential desensitization of
the human 5-HT4(a) receptor expressed in the mouse heart. Therefore, we have used
atrial preparations of transgenic (TG) mice with cardiac myocyte-specific
overexpression of the human 5-HT4(a) receptor and their non-transgenic
littermates (WT). Homologous (by 5-HT) and potentially heterologous (by
isoprenaline) desensitization of the 5-HT4 receptor was investigated in atria of
TG mice. 5-HT increased force of contraction in isolated electrically paced left
atria and beating rate in spontaneously beating right atria only in preparations
from TG but not from WT. Pre-treatment of isolated atria with high concentrations
(10-600 MUM) of 5-HT for 60 min attenuated the positive inotropic effects and the
positive chronotropic effects of 5-HT in TG atria. Several inhibitors of
desensitization including Zn2+, sucrose, and paroxetine were tested. Whereas
sucrose was without any effect and Zn2+ only was partially effective, paroxetine
was able to inhibit desensitization favoring at least in part a G-protein
receptor-coupled kinase-mediated mechanism of 5-HT4 receptor desensitization in
the TG mouse heart. In addition, desensitization of ventricular 5-HT4 receptors
was noted in isolated perfused hearts (Langendorff preparations) from TG mice. In
summary, we show homologous desensitization of the 5-HT4 receptor in the heart of
a transgenic mouse model possibly dependent on active G-protein receptor-coupled
kinase. The exact mechanism and a potentially heterologous desensitization have
to be elucidated by further investigations.
PMID- 28689255
TI - Identification of morin as an agonist of imidazoline I-3 receptor for insulin
secretion in diabetic rats.
AB - Morin is a flavonoid contained in guava that is known to reduce hyperglycemia in
diabetics. Morin has been demonstrated to increase plasma insulin. However, the
mechanism(s) remains unknown. The present study is designed to investigate the
effect of morin on the imidazoline receptor (I-R) that regulates insulin
secretion. We used Chinese hamster ovary (CHO) cells transfected with an I-R
expression construct (NISCH-CHO-K1 cells) to identify the direct effect of morin
on the I-R. Moreover, the imidazoline I3 receptor (I-3R) is known to be present
in pancreatic beta cells and involved in insulin secretion. Therefore, we applied
a specific antagonist (KU14R) to block I-3R in diabetic rats. Additionally, the
effect of morin on insulin secretion was characterized in isolated pancreatic
islets. Morin decreased blood glucose levels by increasing plasma insulin levels
in diabetic rats. In CHO cells expressing an I-R, morin increased calcium influx
in a dose-dependent manner. Additionally, KU14R dose-dependently inhibited the
morin-induced effects, including hypoglycemia and the increase in insulin
secretion and plasma C-peptide levels, in diabetic rats. Furthermore, morin
enhanced insulin secretion from isolated pancreatic islets, and this effect was
also dose-dependently inhibited by KU14R. Phospholipase C (PLC) is known to
couple with the I-R, and a PLC inhibitor dose-dependently attenuated the insulin
secretion induced by morin in isolated pancreatic islets. Taken together, these
data suggest that morin can activate I-3R to enhance insulin secretion.
Therefore, it would be useful to develop morin into a treatment for diabetic
disorders.
PMID- 28689256
TI - Five steps for use and interpretation of troponin in the Emergency Department.
PMID- 28689257
TI - Fluid-attenuated inversion recovery vascular hyperintensities in predicting
cerebral hyperperfusion after intracranial arterial stenting.
AB - PURPOSE: No reliable imaging sign predicting cerebral hyperperfusion after
intracranial arterial stenting (IAS) had been described in the literature. This
study evaluated the effect of fluid-attenuated inversion recovery vascular
hyperintensities (FVHs), also called hyperintense vessel sign on T2-weighted
fluid-attenuated inversion recovery (T2-FLAIR) MR images, in predicting
significant increase in cerebral blood flow (CBF) defined by arterial spin
labeling (ASL) after IAS. METHODS: We reviewed ASL CBF images and T2-FLAIR MR
images before (D0), 1 day after (D1), and 3 days after (D3) IAS of 16 patients.
T1-weighted MR images were used as cerebral maps for calculating CBF. The changes
in CBF values after IAS were calculated in and compared among stenting and
nonstenting vascular territories. An increase more than 50% of CBF was considered
as hyperperfusion. The effect of FVHs in predicting hyperperfusion was
calculated. RESULTS: The D1 CBF value was significantly higher than the D0 CBF
value in stenting vascular, contralateral anterior cerebral artery, contralateral
middle cerebral artery, and contralateral posterior cerebral artery (PCA)
territories (all P < .05). The D1 and D3 CBF values were significantly higher
than the D0 CBF value in overall vascular (P < .001), overall nonstenting
vascular (P < .001), and ipsilateral PCA (P < .05) territories. The rate of more
than 50% increases in CBF was significantly higher in patients who exhibited
asymmetric FVHs than in those who did not exhibit these findings. CONCLUSION:
FVHs could be a critical predictor of a significant increase in CBF after IAS.
PMID- 28689258
TI - Differences in dynamic and static functional connectivity between young and
elderly healthy adults.
AB - PURPOSE: Brain connectivity is highly dynamic, but functional connectivity (FC)
studies using resting-state functional magnetic resonance imaging (rs-fMRI)
assume it to be static. This study assessed differences in dynamic FC between
young healthy adults (YH) and elderly healthy adults (EH) compared to static FC.
METHODS: Using rs-fMRI data from 12 YH and 31 EH, FC was assessed in six
functional regions (subcortical, auditory [AUD], sensorimotor [SM], visuospatial
[VS], cognitive control [CC], and default mode network [DMN]). Static FC was
calculated as Fisher's z-transformed correlation coefficient. The sliding time
window correlation (window size 30 s, step size 3 s) was applied for dynamic FC,
and the standard deviation across sliding windows was calculated. Differences in
static and dynamic FC between EH and YH were calculated and compared by region.
RESULTS: EH showed decreased static FC in the subcortical, CC, and DMN regions
(FDR corrected p = 0.0013; 74 regions), with no regions showing static FC higher
than that in YH. EH showed increased dynamic FC in the subcortical, CC, and DMN
regions, whereas decreased dynamic FC in CC and DMN regions (p < 0.01). However,
the regions showing differences between EH and YH did not overlap between static
and dynamic FC. CONCLUSION: Dynamic FC exhibited differences from static FC in EH
and YH, mainly in regions involved in cognitive control and the DMN. Altered
dynamic FC demonstrated both qualitatively and quantitatively distinct patterns
of transient brain activity and needs to be studied as an imaging biomarker in
the aging process.
PMID- 28689259
TI - Differential diagnosis of parkinsonism by a combined use of diffusion kurtosis
imaging and quantitative susceptibility mapping.
AB - PURPOSE: We investigated whether diffusion kurtosis imaging (DKI) and
quantitative susceptibility mapping (QSM) could detect pathological changes that
occur in Parkinson's disease (PD), multiple system atrophy with predominant
parkinsonism (MSA-P) or predominant cerebellar ataxia (MSA-C), and progressive
supranuclear palsy syndrome (PSPS) and thus be used for differential diagnosis
that is often difficult. METHODS: Seventy patients (41 with PD, 6 with MSA-P, 7
with MSA-C, 16 with PSPS) and 20 healthy controls were examined using a 3.0 T MRI
scanner. From DKI and QSM data, we automatically obtained mean kurtosis (MK),
fractional anisotropy (FA), and mean diffusivity (MD) values of the midbrain
tegmentum (MBT), pontine crossing tract (PCT), and superior/middle cerebellar
peduncles (CPs), which were used to calculate diffusion MBT/PCT ratios (dMPRs)
and diffusion superior/middle CP ratios (dCPRs), as well as MS (magnetic
susceptibility) values of the anterior/posterior putamen (PUa and PUp) and globus
pallidus (GP). RESULTS: dMPRs of MK were significantly decreased in PSPS and
increased in MSA-C compared with the other groups, while dCPRs of MK showed
significant differences only between MSA-C and PD, PSPS, or control. MS values
were significantly increased in the PUp of MSA-P and in the PUa and GP of PSPS
compared with those in PD. The combined use of MK-dMPR and MS-PUp showed
sensitivities of 83-100% and specificities of 81-100% for discriminating among
the disease groups, respectively. CONCLUSION: A quantitative assessment using DKI
and QSM analyses, particularly MK-dMPR and MS-PUp values, can readily identify
patients with parkinsonism.
PMID- 28689260
TI - Extended diffusion weighted magnetic resonance imaging with two-compartment and
anomalous diffusion models for differentiation of low-grade and high-grade brain
tumors in pediatric patients.
AB - PURPOSE: The purpose of this study was to examine advanced diffusion-weighted
magnetic resonance imaging (DW-MRI) models for differentiation of low- and high
grade tumors in the diagnosis of pediatric brain neoplasms. METHODS: Sixty-two
pediatric patients with various types and grades of brain tumors were evaluated
in a retrospective study. Tumor type and grade were classified using the World
Health Organization classification (WHO I-IV) and confirmed by pathological
analysis. Patients underwent DW-MRI before treatment. Diffusion-weighted images
with 16 b-values (0-3500 s/mm2) were acquired. Averaged signal intensity decay
within solid tumor regions was fitted using two-compartment and anomalous
diffusion models. Intracellular and extracellular diffusion coefficients (Dslow
and Dfast), fractional volumes (Vslow and Vfast), generalized diffusion
coefficient (D), spatial constant (MU), heterogeneity index (beta), and a
diffusion index (index_diff = MU * Vslow/beta) were calculated. Multivariate
logistic regression models with stepwise model selection algorithm and receiver
operating characteristic (ROC) analyses were performed to evaluate the ability of
each diffusion parameter to distinguish tumor grade. RESULTS: Among all parameter
combinations, D and index_diff jointly provided the best predictor for tumor
grades, where lower D (p = 0.03) and higher index_diff (p = 0.009) were
significantly associated with higher tumor grades. In ROC analyses of
differentiating low-grade (I-II) and high-grade (III-IV) tumors, index_diff
provided the highest specificity of 0.97 and D provided the highest sensitivity
of 0.96. CONCLUSIONS: Multi-parametric diffusion measurements using two
compartment and anomalous diffusion models were found to be significant
discriminants of tumor grading in pediatric brain neoplasms.
PMID- 28689261
TI - Investigation of cognitive circuits using steady-state cerebral blood volume and
diffusion tensor imaging in patients with mild cognitive impairment following
electrical injury.
AB - PURPOSE: We utilized cerebral blood volume (CBV) magnetic resonance imaging and
diffusion tensor imaging (DTI) to investigate changes in cognitive networks in
patients experiencing cognitive dysfunction following electrical injury. METHODS:
Cognitive function was assessed across various domains, including attention,
verbal memory, executive function, and language. Depressive symptoms were also
evaluated. CBV maps and DTI measures were obtained from 24 patients (age, 41.8 +/
5.8 years; education, 13.3 +/- 1.9 years) and 24 healthy controls (age, 42.3 +/-
2.7 years; education, 14.3 +/- 1.9 years). CBV maps and DTI measures were
compared between patients and controls, and correlations between these measures
and each cognitive assessment score were examined. RESULTS: Patients exhibited
lower attention, verbal memory, and executive function scores than controls (all
p < 0.01). Patients also exhibited higher depression scores than controls (p <
0.01), as well as a predominant increase in CBV in the cerebellar vermis relative
to that of controls (height p < uncorrected 0.001, extent p < corrected 0.05).
Correlation analyses revealed a strong association between executive function
scores and CBV in the bilateral posterior cingulate cortex and left mammillary
body in patients (height p < uncorrected 0.001, extent p < corrected 0.05). There
were no significant differences in DTI measures between patients and controls.
CONCLUSION: The CBV maps showed hypermetabolism in the cerebello-limbic system;
DTI did not find any microstructural changes. Our results suggest that patients
experiencing cognitive dysfunction following electrical injury may possess a
cognitive reserve that protects against deteriorating conditions such as
dementia.
PMID- 28689262
TI - Behavioral mechanisms leading to improved fitness in a subsidized predator.
AB - General mechanisms underlying the distribution and fitness of synanthropic
predators in human-influenced landscapes remain unclear. Under the consumer
resource-matching hypothesis, synanthropes are expected to distribute themselves
among habitats according to resource availability, such that densities are
greater in human-subsidized habitats, but mean individual fitness is equal among
habitats because of negative density dependence. However, "under-matching" to
human food resources can occur, because dominant individuals exclude subordinates
from subsidized habitats and realize relatively high fitness. We integrated
physiological, behavioral, and demographic information to test resource-matching
hypotheses in Steller's jays (Cyanocitta stelleri), a synanthropic nest predator,
to understand how behavior and social systems can influence how synanthropes
respond to food subsidies. Jays consumed more human foods at subsidized (park
campground) sites than jays at unsubsidized (interior forest) sites based on
stable isotope analyses. Jays that occurred at higher densities were in better
body condition (based on feather growth bars and lipid analyses), and had greater
reproductive output at subsidized than unsubsidized sites. Jays with breeding
territories in subsidized sites maintained relatively small home ranges that
overlapped with multiple conspecifics, and exhibited a social system where
dominant individuals typically won contests over food. Thus, jays appeared to be
under-matched to prevalent resource subsidies despite high densities and
behaviors expected to lead to resource matching. Our results also indicate that
local resource subsidies within protected areas can result in source habitats for
synanthropes, potentially impacting sensitive species over broader spatial
scales.
PMID- 28689263
TI - Variation among Consent Forms for Clinical Whole Exome Sequencing.
AB - The goal of this study was to explore variation among informed consent documents
for clinical whole exome sequencing (WES) in order to identify the level of
consistency with the recommendations from the American College of Medical
Genetics and Genomics (ACMG) and the Presidential Commission for the Study of
Bioethical Issues (Bioethics Commission) regarding informed consent for clinical
WES. Recommendations were organized into a framework of key points for analysis.
Content analysis was conducted on a sample of informed consent documents for
clinical WES downloaded from 18 laboratory websites. We observed considerable
variability in the content of informed consent documents among the sample of 18
laboratories. The mean Flesch-Kincaid Grade Level, a measure of readability, of
the consent forms was 10.8, above the recommended 8th grade level. For each of
the individual ACMG and Bioethics Commission recommendations, the frequency of
inclusion ranged from 11% to 100%. For the overall list of 18 consent items,
inclusion ranged from 11 to 17 items (Mean = 13.44, Mode = 14). This analysis
will be useful to laboratories that wish to create informed consent documents
that comply with these recommendations. The consistent use of standardized
informed consent process could improve communication between clinicians and
patients and increase understanding of genetic testing.
PMID- 28689264
TI - Treatment-free remission in patients with chronic myeloid leukemia.
AB - Clinical trials have formally demonstrated that in chronic myeloid leukemia
(CML), patients treated with tyrosine kinase inhibitors (TKI) who achieved and
maintained deep molecular responses could discontinue their treatment after
several years without facing overt signs of disease relapse in approximately 50%
of the cases. In patients with a molecular relapse, prompt re-introduction of TKI
therapy was able to rapidly restore deep molecular responses. The concept of a
lifelong therapy with TKI has thus been challenged and treatment-free remission
(TFR) strategies will soon integrate clinical practice, providing that safe
recommendations will be established. In this article, we give an update on TKI
discontinuation studies in CML and we also provide an overview of upcoming TFR
clinical and biological challenges.
PMID- 28689266
TI - Three-dimensional computer-guided implant placement in oligodontia.
AB - BACKGROUND: The aim of computer-designed surgical templates is to attain higher
precision and accuracy of implant placement, particularly for compromised cases.
PURPOSE: The purpose of this study is to show the benefit of a full three
dimensional virtual workflow to guide implant placement in oligodontia cases
where treatment is challenging due compromised bone quantity and limited
interdental spaces. PATIENT AND METHODS: A full, digitalized workflow was
performed for implant placement in two oligodontia patients. Accuracy was
assessed by calculating the coordinates of the entry point (shoulder) and apex
(tip) as well as the angular deviation of the planned and actual implants.
RESULTS: Implant placement could be well performed with the developed computer
designed templates in oligodontia. Mean shoulder deviation was 1.41 mm (SD 0.55),
mean apical deviation was 1.20 mm (SD 0.54) and mean angular deviation was 5.27
degrees (SD 2.51). CONCLUSION: Application of computer-designed surgical
templates, as described in this technical advanced article, aid in predictable
implant placement in oligodontia where bone quantity is scarce and interdental
spaces are limited.
PMID- 28689267
TI - The novel sRNA s015 improves nisin yield by increasing acid tolerance of
Lactococcus lactis F44.
AB - Nisin, a polycyclic antibacterial peptide produced by Lactococcus lactis, is
stable at low pH. Improving the acid tolerance of L. lactis could thus enhance
nisin yield. Small non-coding RNAs (sRNAs) play essential roles in acid tolerance
by regulating their target mRNAs at the post-transcriptional level. In this
study, a novel sRNA, s015, was identified in L. lactis F44 via the use of RNA
sequencing, qRT-PCR analysis, and Northern blotting. s015 improved the acid
tolerance of L. lactis and boosted nisin yield at low pH. In silico predictions
enabled us to construct a library of possible s015 target mRNAs. Statistical
analysis and validation suggested that s015 contains a highly conserved region
(5'-GAAAAAAAC-3') that likely encompasses the regulatory core of the sRNA. atpG,
busAB, cysD, ilvB, tcsR, ung, yudD, and ywdA were verified as direct targets of
s015, and the interactions between s015 and its target genes were elucidated.
This work provided new insight into the adaptation mechanism of L. lactis under
acid stress.
PMID- 28689265
TI - Aerobic Glycolysis Hypothesis Through WNT/Beta-Catenin Pathway in Exudative Age
Related Macular Degeneration.
AB - Exudative age-related macular degeneration (AMD) is characterized by molecular
mechanisms responsible for the initiation of choroidal neovascularization (CNV).
Inflammatory processes are associated with upregulation of the canonical WNT/beta
catenin pathway in exudative AMD. We focus this review on the link between
WNT/beta-catenin pathway activation and neovascular progression in exudative AMD
through activation of aerobic glycolysis for production of angiogenic factors.
Increased WNT/beta-catenin pathway involves hexokinase 2 (HK2) and pyruvate
kinase M2 (PKM2). WNT/beta-catenin pathway stimulates PI3K/Akt pathway and then
HIF-1alpha which activates glycolytic enzymes: glucose transporter (Glut),
pyruvate dehydrogenase kinase 1 (PDK1), lactate dehydrogenase A (LDH-A), and
monocarboxylate lactate transporter (MCT-1). This phenomenon is called aerobic
glycolysis or the Warburg effect. Consequently, phosphorylation of PDK-1 inhibits
the pyruvate dehydrogenase complex (PDH). Thus, a large part of pyruvate cannot
be converted into acetyl-CoA in mitochondria and only a part of acetyl-CoA can
enter the tricarboxylic acid cycle. Cytosolic pyruvate is converted into lactate
through the action of LDH-A. In exudative AMD, high level of cytosolic lactate is
correlated with increase of VEGF expression, the angiogenic factor of CNV.
Photoreceptors in retina cells can metabolize glucose through aerobic glycolysis
to protect them against oxidative damage, as cancer cells do.
PMID- 28689268
TI - Successful removal of an internal pancreatic stent that migrated into the bile
duct using double-balloon enteroscopy after pancreaticoduodenectomy.
AB - PURPOSE: Internal stents used during pancreaticoduodenectomy (PD) are generally
spontaneously passed through the rectum by defecation. However, we encountered
six patients with internal stents that migrated into the bile duct after PD. We
herein report the outcomes of these six patients and the usefulness of double
balloon enteroscopy (DBE) for removal of such stents from the bile duct. METHODS:
An internal stent was placed across pancreaticojejunostomy in 416 (68.8%) of 605
consecutive patients undergoing PD between 2005 and 2015. This study evaluated
the characteristics and outcomes of the six patients whose internal stent
migrated into the bile duct. RESULTS: Migration of an internal stent into the
bile duct was found during follow-up computed tomography (CT) in 6 (1.4%) of 416
patients who had an internal stent placed during PD. Three patients developed
stent-induced cholangitis, and two had bile duct stones. Excluding one patient
whose internal stent spontaneously slipped out and disappeared from the bile
duct, all patients underwent successful removal of a stent from the bile duct by
a single instance of biliary intervention involving DBE. CONCLUSIONS: Removal of
a stent from the bile duct using DBE is a feasible and useful procedure that
should be considered if an internal stent is detected during follow-up CT after
PD.
PMID- 28689269
TI - Pulmonary endothelial chimerism after hematopoietic stem cell transplantation.
AB - PURPOSE: Few studies have investigated pulmonary endothelial chimerism after
hematopoietic stem cell transplantation. In the present study, we investigated
pulmonary endothelial chimerism using the ABH histo-blood group antigen as an
identifying marker in cases of ABO-incompatible hematopoietic stem cell
transplantation. METHODS: Sixteen lung samples were analyzed. Of these, seven
were explanted lungs from lung transplant recipients with severe pulmonary
chronic graft-versus-host disease (GVHD). The remaining nine were autopsy samples
from patients who died from various causes, and six of these nine cases had a
diagnosis of pulmonary chronic GVHD. The ABH histo-blood group antigen was used
to differentiate donor cells from recipient cells immunohistochemically. We
estimated the percentage of vessels positive for donor blood group antigens in
comparison with the total number of vessels. RESULTS: Donor blood group antigens
were expressed in the endothelium of 13 samples, all of which were pathologically
diagnosed with pulmonary chronic GVHD. The proportion of vessels with donor group
antigens ranged from 0.1 to 17.5%. In contrast, no chimeric vessels were observed
in the three samples without pulmonary chronic GVHD. CONCLUSIONS: Our results
demonstrate that circulating stem cells engraft into the endothelium to a
considerable extent in pulmonary chronic GVHD.
PMID- 28689270
TI - Spiritual Openness, Revisiting a Potentially Important Aspect of Spirituality:
Scale Review and Revision.
AB - Religiousness and spirituality (R/S) exert important influences on individuals
across a range of domains. Spiritual Openness is theoretically linked with the
personality trait of Openness to Experience, suggesting promise for future
research. Using responses from 366 undergraduates on the Spiritual Experience
Index-Revised (SEI-R: subscales of Spiritual Openness and Spiritual Support),
analyses evaluated and revised the SEI-R, deleting poor items and generating a 10
item measure. The new SEI-S exhibits better psychometric properties and reduced
participant burden, and subscales displayed a curvilinear relationship in which
increases in Spiritual Openness showed a trade-off in levels of Spiritual
Support.
PMID- 28689271
TI - Building Capacity Among Laity: A Faith-Based Health Ministry Initiative.
AB - A systematic review of topic-specific faith-based health programs determined that
health outcomes can be improved though faith-based health interventions. A
university research team, in partnership with the Kansas United Methodist Church
and a United Methodist philanthropy, facilitated planning and development of a
statewide initiative to increase the capacity of laity-led health ministry teams.
The purpose of this paper is to describe the processes utilized to design and
implement an initiative to increase capacity for laity-led comprehensive health
ministry among Kansas United Methodist Church congregations and to share the key
elements of the initiative.
PMID- 28689272
TI - Insulin does not rescue cortical and trabecular bone loss in type 2 diabetic Goto
Kakizaki rats.
AB - In type 2 diabetes mellitus (T2DM), the decreased bone strength is often
associated with hyperglycemia and bone cell insulin resistance. Since T2DM is
increasingly reported in young adults, it is not known whether the effect of T2DM
on bone would be different in young adolescents and aging adults. Here, we found
shorter femoral and tibial lengths in 7-month, but not 13-month, Goto-Kakizaki
(GK) T2DM rats as compared to wild-type rats. Bone uCT analysis showed long
lasting impairment of both cortical and trabecular bones in GK rats. Although
insulin treatment effectively improved hyperglycemia, it was not able to rescue
trabecular BMD and cortical thickness in young adult GK rats. In conclusion,
insulin treatment and alleviation of hyperglycemia did not increase BMD of
osteopenic GK rats. It is likely that early prevention of insulin resistance
should prevail over treatment of full-blown T2DM-related osteopathy.
PMID- 28689273
TI - Locking attachment plate fixation around a well-fixed stem in periprosthetic
femoral shaft fractures.
AB - INTRODUCTION: Periprosthetic fractures are difficult to manage. Plating technique
has been considered a reliable form of management of periprosthetic fractures
with a well-fixed stem, but a dependable and stable method of plate fixation to
the bone is lacking. This study reports the clinical results using a locking
attachment plate (LAP) instead of cable fixation to fix locking plates to a
periprosthetic femoral shaft fracture. MATERIALS AND METHODS: Nineteen patients
with periprosthetic femoral shaft fractures around well-fixed stemmed implants
were studied between August 2012 and December 2014. Patients were followed up for
at least 1 year postoperatively. Median age was 74 years (range 56-96 years).
Fractures were classified according to the Unified Classification System,
Vancouver classification, and Su classification. PROCEDURE: Open reduction was
performed under minimal incision and the locking plate was fixed to the lateral
cortex of the femoral shaft. The part of the shaft without a stem was fixed to
the plate using 5.0-mm locking screws, and the part with an underlying stem was
fixed using 3.5-mm locking screws through the LAP instead of cables.
Postoperatively, patients were managed using general principles for femoral shaft
fractures. RESULTS: Average follow-up was 16 months (range 12-36 months). All
cases achieved fracture healing without loss of reduction. There were no cases of
implant breakage or stem loosening at final follow-up. The average number of LAPs
per fixation construct was 2.1 (range 1-4), and the average number of 3.5-mm
locking screws through each LAP was 3.3 (range 2-4). The average value of plate
screw density was 0.55 (range 0.37-0.8), and the average working length was four
holes (range 2-8). CONCLUSIONS: Using the LAP to manage periprosthetic fractures
with a well-fixed stem could obviate the need for cable around the stem area and
yield acceptable outcomes.
PMID- 28689274
TI - Impact of glutathione transferases genes polymorphisms in nevirapine adverse
reactions: a possible role for GSTM1 in SJS/TEN susceptibility.
AB - PURPOSE: Nevirapine (NVP) is used in developing countries as first-line treatment
of HIV infection. Unfortunately, its use is associated with common serious
adverse drug reactions, such as liver toxicity and the most severe and rare
Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). GSTT1 and
GSTM1 genes code for enzymes involved in the metabolism of a wide range of drugs.
We hypothesized that this gene variability could be implicated in NVP adverse
reactions. METHODS: We analyzed the GSTM1 and GSTT1 null genotypes by multiplex
PCR in a population of 181 patients from Mozambique, treated with NVP. A
case/control association study was performed. We also counted the number of risk
alleles in SJS/TEN patients and in controls, including the GSTM1 null genotype
and four previously identified risk alleles in CYP2B6, HCP5, and TRAF3IP2 genes.
RESULTS: Among patients, 27 had developed SJS/TEN and 76 had developed
hepatotoxicity during the treatment. The GSTM1 null genotype was more frequent in
the cases with SJS/TEN than in the controls (OR = 2.94, P = 0.027). This
association is also observed when other risk factors are taken into account, by a
multivariate analysis (P = 0.024 and OR = 3.58). The risk allele counting
analysis revealed a significantly higher risk for SJS/TEN in patients carrying
three or four risk alleles. Moreover, all subjects with five or six risk alleles
developed SJS/TEN, while subjects without any risk alleles were present only in
the control group. CONCLUSIONS: We observed an association between GSTM1 and
SJS/TEN susceptibility. Moreover, GSTM1 contributes to the definition of a
genetic risk profile for SJS/TEN susceptibility.
PMID- 28689275
TI - Neuroprotective Effects of n-3 Polyunsaturated Fatty Acid-Enriched
Phosphatidylserine Against Oxidative Damage in PC12 Cells.
AB - Neurodegenerative diseases are defined by progressive loss of specific neuronal
cell populations and are associated with protein aggregates. Oxidative stress has
been implicated in their pathological processes. Previous studies revealed that
docosahexaenoic acid (DHA) is beneficial in neurodegenerative diseases.
Phospholipids (PLs) derived from marine products are rich in DHA and
eicosapentaenoic acid (EPA). In the present study, we investigated the
neuroprotective effects of DHA-enriched and unenriched phosphatidylcholine (PC)
and phosphatidylserine (PS) on oxidative stress induced by hydrogen peroxide
(H2O2) and tert-butylhydroperoxide in PC12 cells. Cell viability and leakage of
lactate dehydrogenase results showed that the neuroprotective effect of PS was
superior to that of PC. DHA- and EPA-enriched PC and PS were superior to that
without DHA or EPA; in addition, the improvement with n-3 polyunsaturated fatty
acid-enriched PS (n-3 PS) was dose dependent. Acridine orange/ethidium bromide
staining showed that DHA- and EPA-enriched PS (DHA/EPA-PS) could significantly
inhibit apoptosis. Mechanistic studies revealed that EPA-PS and DHA-PS were
effective to increase superoxide dismutase (SOD) levels by 48.4 and 58.2 % and
total antioxidant capacity (T-AOC) level by 51 and 94 %, respectively, in the
H2O2 model. Similar results for SOD and T-AOC levels were shown in the t-BHP
model. EPA/DHA-PS could downregulate the messenger RNA level of Caspase-3,
Caspase-9, and Bax, upregulate Bcl-2, inhibit Bax, and increase Bcl-2 at protein
level. In conclusion, EPA/DHA-PS could protect PC12 cells from oxidative stress
and prevent mitochondrial-mediated apoptosis. Our findings indicate that the
neuroprotective effects of DHA/EPA-PLs depend on the molecular form. Further
studies are necessary to reveal detailed mechanisms and structure-effect
relationships.
PMID- 28689276
TI - Low genetic variation in the MHC class II DRB gene and MHC-linked microsatellites
in endangered island populations of the leopard cat (Prionailurus bengalensis) in
Japan.
AB - Isolated populations of the leopard cat (Prionailurus bengalensis) on Tsushima
and Iriomote islands in Japan are classified as subspecies P. b. euptilurus and
P. b. iriomotensis, respectively. Because both populations have decreased to
roughly 100, an understanding of their genetic diversity is essential for
conservation. We genotyped MHC class II DRB exon 2 and MHC-linked microsatellite
loci to evaluate the diversity of MHC genes in the Tsushima and Iriomote cat
populations. We detected ten and four DRB alleles in these populations,
respectively. A phylogenetic analysis showed DRB alleles from both populations to
be closely related to those in other felid DRB lineages, indicating trans-species
polymorphism. The MHC-linked microsatellites were more polymorphic in the
Tsushima than in the Iriomote population. The MHC diversity of both leopard cat
populations is much lower than in the domestic cat populations on these islands,
probably due to inbreeding associated with founder effects, geographical
isolation, or genetic drift. Our results predict low resistance of the two
endangered populations to new pathogens introduced to the islands.
PMID- 28689277
TI - Identification of the Aggregation-sex Pheromone Produced by Male Monochamus
saltuarius, a Major Insect Vector of the Pine Wood Nematode.
AB - In this study, we isolated and identified an aggregation-sex pheromone from
Monochamus saltuarius, the major insect vector of the pine wood nematode in
Korea. Adult males of M. saltuarius produce 2-undecyloxy-1-ethanol, which is
known as an aggregation-sex pheromone in other Monochamus species. We performed
field experiments to determine the attractiveness of the pheromone and other
synergists. More M. saltuarius adult beetles were attracted to traps baited with
the pheromone than to unbaited traps. Ethanol and (-)-alpha-pinene interacted
synergistically with the pheromone. Traps baited with the pheromone + (-)-alpha
pinene +ethanol were more attractive to M. saltuarius adults than traps baited
with the pheromone, (-)-alpha-pinene, or ethanol alone. Ipsenol, ipsdienol, and
limonene were also identified as synergists of the aggregation-sex pheromone for
M. saltuarius adults. In field experiments, the proportion of females was much
higher in the beetles caught in traps than among the beetles emerging from
naturally-infested logs in the laboratory. Our results suggest that a combination
of aggregation-sex pheromone and synergists could be very effective for
monitoring and managing M. saltuarius.
PMID- 28689278
TI - Maternal serum homocysteine and uterine artery Doppler as predictors of
preeclampsia and poor placentation.
AB - PURPOSE: The aim of this study was to evaluate the role of maternal serum total
Homocysteine (tHcy) and uterine artery (Ut-A) Doppler as predictors of
preeclampsia (PE), intrauterine growth restriction (IUGR), and other
complications related to poor placentation. PATIENTS AND METHODS: A prospective
cohort study was conducted on 500 women with spontaneous pregnancies. tHcy was
measured at 15-19 weeks, and then, Ut-A Doppler was performed at 18-22 weeks of
pregnancy. RESULTS: 453 pregnant women completed the follow-up of the study. The
tHcy and Ut-A resistance index were significantly higher in women who developed
PE, IUGR, and other complications when compared to controls (tHcy: 7.033 +/-
2.744, 6.321 +/- 3.645, and 6.602 +/- 2.469 vs 4.701 +/- 2.082 MUmol/L,
respectively, p value <0.001 and Ut-A resistance index: 0.587 +/- 0.072, 0.587 +/
0.053, and 0.597 +/- 0.069 vs 0.524 +/- 0.025, respectively, p value <0.001).
The use of both tHcy assessment and Ut-A Doppler improved the sensitivity of
prediction of PE relative to the use of each one alone (85.2 relative to 73.33
and 60%, respectively). CONCLUSION: The use of elevated homocysteine and uterine
artery Doppler screening are valuable in prediction of preeclampsia, IUGR, and
poor placentation disorders. CLINCALTRIAL. GOV ID: NCT02854501.
PMID- 28689279
TI - Three-dimensional culture of a genetically modified hepatoma cell line using
macroporous gelatin beads.
AB - Hepatoma cells are a candidate cell source for bio-artificial livers. However,
they exhibit reduced liver functions compared with primary hepatocytes. In our
previous study, genetically engineered mouse hepatoma cells were created by
transduction with vectors mediating inducible overexpression of eight liver
enriched transcription factors. Upon the induction of the liver-enriched
transcription factors transduced, the cells expressed both phenotypic and
genotypic liver functions at high levels. In the present study, we performed
three-dimensional culture of these cells using macroporous gelatin beads. When
immobilized on the macroporous gelatin beads, these cells exhibited further
enhancement in liver functionality, including increased albumin secretion,
ammonia removal and cytochrome P450 activity. The levels of these functions were
significantly enhanced compared to monolayer culture. The method is simple and
scalable, and provides highly functional cells that can be used in basic and
applied fields of hepatic research.
PMID- 28689280
TI - Analysis of toxicity effects of Di-(2-ethylhexyl) phthalate exposure on human
bronchial epithelial 16HBE cells.
AB - Recent studies have indicated that Di-(2-ethylhexyl) phthalate (DEHP), the most
commonly used plasticizer in daily-life products, could be dispersed in indoor
air and induce human exposure via inhalation. DEHP has been reported to have
effects on the respiratory system in both animal and human researches. The
toxicity effects of DEHP exposure on cell proliferation, cell cycle progression,
apoptosis, global DNA methylation and the expression levels of DNA
methyltransferases (DNMTs) were investigated in this study, using human
epithelial cell line 16HBE as an in vitro model. Cells were treated with DEHP at
doses of 0, 0.125, 0.5 and 2 mmol/L for 48 h. Cell proliferation, cell cycle and
apoptosis were tested by MTT assay and flow cytometer, respectively. The obtained
results showed decreased living cell number and cell viability following DEHP
exposure at the dose of 2 mmol/L. DEHP also inhibited the cell cycle progression
of G1 phase and induced a significant increase in cell apoptosis in 16HBE cells.
DEHP exposure could induce cell proliferation inhibition in 16HBE cells via the
blocking of cell cycle progression and accelerated cell apoptosis. In addition,
decreased global DNA methylation levels and expression levels of DNMTs were
observed in DEHP-treated groups which revealed possible epigenetic effects of
DEHP.
PMID- 28689281
TI - Optimal FDG PET/CT volumetric parameters for risk stratification in patients with
locally advanced non-small cell lung cancer: results from the ACRIN 6668/RTOG
0235 trial.
AB - PURPOSE: In recent years, multiple studies have demonstrated the value of
volumetric FDG-PET/CT parameters as independent prognostic factors in patients
with non-small cell lung cancer (NSCLC). We aimed to determine the optimal cut
off points of pretreatment volumetric FDG-PET/CT parameters in predicting overall
survival (OS) in patients with locally advanced NSCLC and to recommend imaging
biomarkers appropriate for routine clinical applications. METHODS: Patients with
inoperable stage IIB/III NSCLC enrolled in ACRIN 6668/RTOG 0235 were included.
Pretreatment FDG-PET scans were quantified using semiautomatic adaptive contrast
oriented thresholding and local-background partial-volume-effect-correction
algorithms. For each patient, the following indices were measured: metabolic
tumor volume (MTV), total lesion glycolysis (TLG), SUVmax, SUVmean, partial
volume-corrected TLG (pvcTLG), and pvcSUVmean for the whole-body, primary tumor,
and regional lymph nodes. The association between each index and patient outcome
was assessed using Cox proportional hazards regression. Optimal cut-off points
were estimated using recursive binary partitioning in a conditional inference
framework and used in Kaplan-Meier curves with log-rank testing. The
discriminatory ability of each index was examined using time-dependent receiver
operating characteristic (ROC) curves and corresponding area under the curve
(AUC(t)). RESULTS: The study included 196 patients. Pretreatment whole-body and
primary tumor MTV, TLG, and pvcTLG were independently prognostic of OS. Optimal
cut-off points were 175.0, 270.9, and 35.5 cm3 for whole-body TLG, pvcTLG, and
MTV, and were 168.2, 239.8, and 17.4 cm3 for primary tumor TLG, pvcTLG, and MTV,
respectively. In time-dependent ROC analysis, AUC(t) for MTV and TLG were
uniformly higher than that of SUV measures over all time points. Primary tumor
and whole-body parameters demonstrated similar patterns of separation for those
patients above versus below the optimal cut-off points in Kaplan-Meier curves and
in time-dependent ROC analysis. CONCLUSION: We demonstrated that pretreatment
whole-body and primary tumor volumetric FDG-PET/CT parameters, including MTV,
TLG, and pvcTLG, are strongly prognostic for OS in patients with locally advanced
NSCLC, and have similar discriminatory ability. Therefore, we believe that, after
validation in future trials, the derived optimal cut-off points for primary tumor
volumetric FDG-PET/CT parameters, or their more refined versions, could be
incorporated into routine clinical practice, and may provide more accurate
prognostication and staging based on tumor metabolic features.
PMID- 28689282
TI - High molecular weight fibroblast growth factor-2 as a promising prognostic
biomarker to predict the occurrence of heart failure in atrial fibrillation
patients.
AB - Heart failure (HF) has a significant effect on the prognosis of the patients with
atrial fibrillation (AF), and also it is an important risk factor for overall
mortality. High molecular weight fibroblast growth factor-2 (Hi-FGF-2) is
emerging as a prognostic marker with HF and AF. The aim of this study was to
prove that Hi-FGF-2 would predict occurrence of HF in the patients with AF.
Subjects diagnosed with paroxysmal AF (Group paAF), persistent AF (Group peAF)
and sinus rhythm (Group SR) were enrolled in the study. Serum Hi-FGF-2
concentration was measured by ELISA at baseline. Multivariable logistic models
and receiver operating characteristic (ROC) curve analysis were established to
predict the prognosis of AF subjects. 260 patients were enrolled in the study:
104 (40.0%) admitted for sinus rhythm (Group SR) and 156 (60.0%) with AF (Group
paAF and Group peAF). The Hi-FGF-2 levels were much lower in the Group SR (58.2
+/- 27.1 ng/L) than in the Group AF. Furthermore, the Group peAF (84.3 +/- 34.1
ng/L) had higher Hi-FGF-2 levels than the Group paAF (72.9 +/- 35.8 ng/L). Serum
Hi-FGF-2 levels were classified into trisection in the multivariable logistic
model (T1 < 57.3 ng/L, 57.3 < T2 < 86.5 ng/L, and T3 > 86.5 ng/L). Hi-FGF-2
showed good predictive ability for new-onset HF in the patients with AF. The
occurrence of HF was associated significantly with increased tertile of serum Hi
FGF-2 levels (T2: OR 5.922, 95% CI 1.109-31.626, P = 0.037 and T3: OR 8.262, 95%
CI 1.735-39.343, P = 0.008). ROC curve analysis showed that the area under curves
for Hi-FGF-2 were 0.720 (P < 0.0001). Hi-FGF-2 has a significant meaning in AF
subjects. Further to this, higher circulating Hi-FGF-2 was highly related to
persistent AF, and Hi-FGF-2 may be an independent risk factor of occurrence HF in
AF subjects.
PMID- 28689283
TI - Diffusion-weighted imaging for the cellularity assessment and matrix
characterization of soft tissue tumour.
AB - PURPOSE: To evaluate whether apparent diffusion coefficient (ADC) of diffusion
weighted imaging (DWI) is able to investigate the histological features of soft
tissue tumours. METHODS: We reviewed MRIs of soft tissue tumours performed from
2012 to 2015 to calculate the average ADCs. We included 46 patients (27 male;
mean age: 57 years, range 12-85 years) with histologically proven soft tissue
tumours (10 benign, 2 intermediate 34 malignant) grouped into eight tumour type
classes. An experienced pathologist assigned a semi-quantitative cellularity
score (very high, high, medium and low) and tumour grading. The t test, ANOVA and
linear regression were used to correlate ADC with clinicopathological data.
Approximate receiver operating characteristic curves were created to predict
possible uses of ADC to differentiate benign from malignant tumours. RESULTS:
There was a significant difference (p < 0.01) in ADCs between these three groups
excluding myxoid sarcomas. A significant difference was also evident between the
tumour type classes (p < 0.001), grade II and III myxoid lesions (p < 0.05),
tumour grading classes (p < 0.001) and cellularity scores classes (p < 0.001),
with the lowest ADCs in the very high cellularity. While the linear regression
analysis showed a significant relationship between ADC and tumour cellularity (r
= 0.590, p <= 0.05) and grading (r = 0.437, p <= 0.05), no significant
relationship was found with age, gender, tumour size and histological subtype. An
optimal cut-off ADC value of 1.45 * 10-3 mm2/s with 76.8% accuracy was found to
differentiate benign from malignant tumours. CONCLUSIONS: DWI may offer
adjunctive information about soft tissue tumours, but its clinical role is still
to be defined.
PMID- 28689284
TI - Erratum to: Bio-transfer factors and temporal variation of heavy metals in
different sexes of 3 species of edible brackish water fish.
PMID- 28689285
TI - Eragrostis plana Nees as a novel eco-friendly adsorbent for removal of crystal
violet from aqueous solutions.
AB - Eragrostis plana Nees (EPN) was used as new and eco-friendly adsorbent for the
removal of crystal violet dye (CV) from aqueous solution. Specific surface area
(BET), scanning electron microscopy (SEM), infrared spectroscopy (ATR-FTIR),
point of zero charge (pHPZC), and modified Boehm titration method were used to
characterize the EPN material. The effects of initial pH of solution, adsorbent
mass, contact time and initial dye concentration, and temperature were studied in
batch adsorption mode. Kinetic data were evaluated by pseudo-first-order and
pseudo-second-order models. The result exhibited that pseudo-second-order model
well described the adsorption kinetics of CV onto EPN. Langmuir, Freundlich, and
Sips isotherm models were used for analysis of the isothermal data. The
equilibrium data of adsorption of CV onto EPN was better fitted with the Sips
isotherm. Based on the Sips isotherm model, the maximum adsorption capacity was
76.20 +/- 1.20 mg g-1 at 333 K. A high desorption of CV from EPN was obtained
using 1.00 mol L-1 of CH3COOH as eluent. The thermodynamic data indicated that
the adsorption was spontaneous, endothermic, and physical process. EPN can be
used as alternative adsorbent to remove CV from aqueous solution.
PMID- 28689286
TI - Investigation on the removal of H2S from microwave pyrolysis of sewage sludge by
an integrated two-stage system.
AB - In this study, an integrated two-stage system, including the in-situ catalytic
microwave pyrolysis (ICMP) and subsequent catalytic wet oxidation (CWO)
processes, was proposed to remove H2S released from microwave-induced pyrolysis
of sewage sludge. The emission profile and H2S removal from the pyrolysis of raw
sewage sludge (SS) and sewage sludge spiked with conditioner CaO (SS-CaO) were
investigated. The results showed that CaO played a positive role on sulfur
fixation during the pyrolysis process. It was found that SS-CaO (10 wt.%)
contributed to about 35% of H2S removal at the first stage (ICMP process).
Additionally, the CWO process was demonstrated to have promising potential for
posttreatment of remaining H2S gas. At the Fe3+ concentration of 30 g/L, the
maximum H2S removal efficiency of 94.8% was obtained for a single Fe3+/Cu2+
solution. Finally, at the pyrolysis temperature of 800 degrees C, 99.7% of H2S
was eliminated by the integrated two-stage system meeting the discharge standard
of China. Therefore, the integrated two-stage system of ICMP + CWO may provide a
promising strategy to remove H2S dramatically for the biomass pyrolysis industry.
PMID- 28689287
TI - Kinetics, isotherm, and thermodynamic studies of methylene blue adsorption from
water by Mytella falcata waste.
AB - This work evaluates the application of Mytella falcata shells, discarded in large
quantities in the state of Alagoas, Brazil, as adsorbent for methylene blue dye
(MB). It was investigated how the amount of adsorbent (M), the average particle
diameter (G), and the agitation speed (A) affected the adsorption. Kinetic and
equilibrium studies were conducted, and the pseudo-second-order equation
adequately represented the kinetic data and isotherms following Liu's model (q
max = 8.81 mg g-1 at 60 degrees C). The adsorption was spontaneous, favorable,
and endothermic. Mytella falcata shell is a suitable adsorbent for MB and could
potentially contribute to its removal from the environment.
PMID- 28689288
TI - Vermi-modification of ruminant excreta using Eisenia fetida.
AB - Present investigation aims on the vermicomposting of the excreta of different
ruminants to convert it into manure employing earthworm species, Eisenia fetida.
A total of 11 feedstocks (FS1-FS11) with different ratios were prepared from the
excreta of different ruminants, viz., sheep, cow, buffalo, and goat. Semi
composted feedstocks were fed to E. fetida for 90 days under laboratory
conditions. Vermicomposting enhanced the nutrient contents of ruminant excreta
and converted it into odor-free and homogenous vermicompost. The growth of E.
fetida was significant in all the feedstocks, but largest biomass gain was
achieved in buffalo excreta followed by [sheep + buffalo] > [goat + buffalo] and
[cow + buffalo] feedstocks. Highest fecundity (782 +/- 23.3) was also recorded in
buffalo excreta followed by [goat + buffalo] excreta feedstock (484.6 +/- 15.7).
In vermicomposted feedstocks, total organic carbon and organic matter was lesser,
while NPK and heavy metals were higher as compared to raw feedstocks. C/N ratios
of vermicomposts ranged from 15.37 to 38.56, which indicate a good level of
maturity and stabilization of feedstocks.
PMID- 28689289
TI - Optimal scale of China's cities under the maximization of economic benefits and
environmental benefits.
AB - The cities are the consumption concentration of energy, resources, and the
concentration of CO2 emissions. The cities' area only accounted for 2% in the
world's surface; however, their population accounted for about 50% of the total
population, and CO2 emissions accounted for about 80% of the total emissions. The
cities lie in a key position in solving the global climate change. China's
urbanization level was just exceeding by 50%, which was in the intermediate stage
of urbanization. The rapid development of the urbanization process and the
expansion of city scale have brought economic growth and all kinds of
environmental issues. Therefore, is there an optimal city scale which can make
cities maintain economic growth and can also reduce or even avoid the
environmental problems in the meantime? The question deserves deep research.
Based on the background, the data from 1998 to 2014, and the goals of the cities'
economic and environmental benefits, this paper builds the optimal scale model
for the cities, and obtain two conclusions: (1) in a certain period and range,
the cities have the optimal scale; (2) for the cities in China, the optimal scale
is about 1.78 million people.
PMID- 28689290
TI - Ricinus communis L. (castor bean) as a potential candidate for revegetating
industrial waste contaminated sites in peri-urban Greater Hyderabad: remarks on
seed oil.
AB - Ricinus communis L. (castor bean or castor oil plant) was found growing on metal
contaminated sites (4) of peri-urban Greater Hyderabad comprises of erstwhile
industrial areas viz Bollaram, Patancheru, Bharatnagar, and Kattedan industrial
areas. During 2013-2017, about 60 research papers have appeared focusing the role
of castor bean in phytoremediation of co-contaminated soils, co-generation of
biomaterials, and environmental cleanup, as bioenergy crop and sustainable
development. The present study is focused on its use as a multipurpose
phytoremediation crop for phytostabilization and revegetation of waste disposed
peri-urban contaminated soils. To determine the plant tolerance level, metal
accumulation, chlorophyll, protein, proline, lipid peroxidation, oil content, and
soil properties were characterized. It was noticed that the castor plant and
soils have high concentration of metals such as cadmium (Cd), lead (Pb), iron
(Fe), manganese (Mn), and zinc (Zn). The soils have high phosphorous (P),
adequate nitrogen (N), and low concentration of potassium (K). Iron (Fe)
concentrations ranged from1672+/-50.91 to 2166+/-155.78 mg kg-1 in the soil. The
trend of metal accumulation Fe>Zn>Mn>Pb>Cd was found in different plant parts at
polluted sites. The translocation of Cd and Pb showed values more than one in
industrial areas viz Bollaram, Kattedan, and Bharatnagar indicating the plants
resistance to metal toxicity. Chlorophyll and protein content reduced while
proline and malondialdehyde increased due to its tolerance level under metal
exposure. The content of ricinoleic acid was higher, and the fatty acids
composition of polluted areas was almost similar to that of the control area.
Thus, R. communis L. can be employed for reclamation of heavy metal contaminated
soils.
PMID- 28689291
TI - TiO2-SnS2 nanocomposites: solar-active photocatalytic materials for water
treatment.
AB - The study is aimed at evaluating TiO2-SnS2 composites as effective solar-active
photocatalysts for water treatment. Two strategies for the preparation of TiO2
SnS2 composites were examined: (i) in-situ chemical synthesis followed by
immobilization on glass plates and (ii) binding of two components (TiO2 and SnS2)
within the immobilization step. The as-prepared TiO2-SnS2 composites and their
sole components (TiO2 or SnS2) were inspected for composition, crystallinity, and
morphology using Fourier transform infrared spectroscopy (FTIR),
thermogravimetric analysis (TGA), X-ray diffraction (XRD), and scanning electron
microscopy/energy-dispersive X-ray spectroscopy (SEM/EDX) analyses. Diffuse
reflectance spectroscopy (DRS) was used to determine band gaps of immobilized
TiO2-SnS2 and to establish the changes in comparison to respective sole
components. The activity of immobilized TiO2-SnS2 composites was tested for the
removal of diclofenac (DCF) in aqueous solution under simulated solar irradiation
and compared with that of single component photocatalysts. In situ chemical
synthesis yielded materials of high crystallinity, while their morphology and
composition strongly depended on synthesis conditions applied. TiO2-SnS2
composites exhibited higher activity toward DCF removal and conversion in
comparison to their sole components at acidic pH, while only in situ synthesized
TiO2-SnS2 composites showed higher activity at neutral pH.
PMID- 28689292
TI - Estimating the Economic Value of Information for Screening in Disseminating and
Targeting Effective School-based Preventive Interventions: An Illustrative
Example.
AB - When candidates for school-based preventive interventions are heterogeneous in
their risk of poor outcomes, an intervention's expected economic net benefits may
be maximized by targeting candidates for whom the intervention is most likely to
yield benefits, such as those at high risk of poor outcomes. Although increasing
amounts of information about candidates may facilitate more accurate targeting,
collecting information can be costly. We present an illustrative example to show
how cost-benefit analysis results from effective intervention demonstrations can
help us to assess whether improved targeting accuracy justifies the cost of
collecting additional information needed to make this improvement.
PMID- 28689293
TI - Predictors of shoulder level after spinal fusion in adolescent idiopathic
scoliosis.
AB - BACKGROUND: For patients with adolescent idiopathic scoliosis, shoulder balance
influences their treatment satisfaction and psychological well-being. Several
parameters are known to affect postoperative shoulder balance, but few prognostic
models are as yet available. PURPOSE: This study aimed to identify independent
predictive factors that can be used to assess preoperatively which patients are
at risk of postoperative shoulder elevation, and to build a linear prediction
model. METHODS: N = 102 patients with all Lenke types were reviewed
radiographically before surgery and 1 year afterward. The outcome measures were
coracoid height difference (CHD), clavicular angle (CA), and clavicle-first rib
intersection difference (CiRID). Predictive factors commonly used in the
literature were investigated using correlation analysis and statistical testing.
Significant contributing factors were included in three multiple linear
regression models (for CHD, CA, and CiRID). RESULTS: The mean shoulder level
(CHD) significantly changed from a lower left shoulder value of -8.5 mm before
surgery to 3.3 mm at the follow-up examination. A high preoperative left shoulder
level by CiRID, a large amount of Cobb angle correction of the distal thoracic
curve, a low preoperative Cobb angle in the lumbar curve, and a structural
proximal thoracic curve proved to be determinants and thus risk factors for left
sided shoulder elevation after surgery. The three models predicting CHD, CA, and
CiRID at the follow-up examination included these four risk factors and were
significant. CONCLUSIONS: Preoperative variables have the strongest influence on
shoulder level after spinal instrumentation. Additionally, extensive correction
of the distal thoracic curve can cause elevation of the left shoulder.
PMID- 28689294
TI - Cerebellar disease associated with anti-glutamic acid decarboxylase antibodies:
review.
AB - Several neurological syndromes have been recognized associated to GAD antibodies.
Among those disorders, cerebellar ataxia (CA) is one of the most common, along
with stiff-person syndrome. Patients with GAD associated CA present with a
progressive pancerebellar syndrome, with a subacute or chronic evolution, along
with other neurological manifestations such as stiffness, oculomotor dysfunction,
epilepsy, and cognitive dysfunction. These symptoms may be preceded by the so
called "brainstem attacks", where manifestations consistent with transient
dysfunction of the brainstem may be observed. These patients frequently have
extra-neurologic autoimmune manifestations such as diabetes mellitus type 1,
polyendocrine autoimmune syndrome, pernicious anemia, vitiligo, etc. A proportion
of patients may present with an underlying neoplasia, but the course is less
aggressive than in those patients with classical paraneoplastic CA with
onconeural antibodies. The diagnosis is based on the present of high serum and
CSF titers of GAD antibodies, with intrathecal production of such antibodies.
Treatment is aimed to decrease the immunological response with intravenous
immunoglobulin, steroids, rituximab and oral immunosuppressive drugs. A subacute
presentation and rapid initiation of immunotherapy seem to be the predictors of a
favorable clinical response.
PMID- 28689295
TI - Inhibitory rTMS applied on somatosensory cortex in Wilson's disease patients with
hand dystonia.
AB - Hand dystonia is a common complication of Wilson's disease (WD), responsible for
handwriting difficulties and disability. Alteration of sensorimotor integration
and overactivity of the somatosensory cortex have been demonstrated in dystonia.
This study investigated the immediate after effect of an inhibitory repetitive
transcranial magnetic stimulation (rTMS) applied over the somatosensory cortex on
the writing function in WD patients with hand dystonia. We performed a pilot
prospective randomized double-blind sham-controlled crossover rTMS study. A 20
min 1-Hz rTMS session, stereotaxically guided, was applied over the left
somatosensory cortex in 13 WD patients with right dystonic writer's cramp. After
3 days, each patient was crossed-over to the alternative treatment. Patients were
clinically evaluated before and immediately after each rTMS session with the
Unified Wilson's Disease rating scale (UWDRS), the Writers' Cramp Rating Scale
(WCRS), a specifically designed scale for handwriting difficulties in Wilson's
disease patients (FAR, flow, accuracy, and rhythmicity evaluation), and a visual
analog scale (VAS) for handwriting discomfort. No significant change in UWDRS,
WCRS, VAS, or FAR scores was observed in patients treated with somatosensory
inhibitory rTMS compared to the sham protocol. The FAR negatively correlated with
UWDRS (r = -0.6; P = 0.02), but not with the WCRS score, disease duration, MRI
diffusion lesions, or with atrophy scores. In our experimental conditions, a
single inhibitory rTMS session applied over somatosensory cortex did not improve
dystonic writer cramp in WD patients.
PMID- 28689296
TI - Development of auditory sensitivity in the barn owl.
AB - Adult barn owl hearing is acute, but development of this sense is not well
understood. We, therefore, measured auditory brainstem responses in barn owls
from before the onset of hearing (posthatch day 2, or P2) to adulthood (P69). The
first consistent responses were detected at P4 for 1 and 2 kHz, followed by
responses to 0.5 and 4 kHz at P9, and 5 kHz at P13. Sensitivity to higher
frequencies increased with age, with responses to 12 kHz appearing about 2 months
after hatching, once the facial ruff was mature. Therefore, these altricial birds
achieve their sensitivity to sound during a prolonged period of development,
which coincides with maturation of the skull and facial ruff (Haresign and
Moiseff in Auk 105:699-705, 1988).
PMID- 28689298
TI - Short infusion of paclitaxel imbalances plasmatic lipid metabolism and correlates
with cardiac markers of acute damage in patients with breast cancer.
AB - PURPOSE: Although paclitaxel-based chemotherapy is widely used for treating
breast cancer, paclitaxel therapy has been associated with several adverse
effects. Such adverse effects have primarily been associated with long-term
regimens, but some acute effects are being increasingly reported in the
literature. In this context, the present study analyzed the systemic proteomic
profiles of women diagnosed with breast cancer at the first cycle of short
paclitaxel infusion (n = 30). Proteomic profiles thus obtained were compared with
those of breast cancer patients without chemotherapy (n = 50), as well as with
those of healthy controls (n = 40). METHODS: Plasma samples were evaluated by
label-free LC-MS to obtain systemic proteomic profiles. Putative dysregulated
pathways were identified and validated by in silico analysis of proteomic
profiles. RESULTS: Our results identified 188 proteins that were differentially
expressed in patients who received a single short paclitaxel infusion when
compared to patients who did not receive the infusion. Gene ontology analysis
indicated that the cholesterol pathway may be dysregulated by paclitaxel in these
patients. Validation analysis showed that paclitaxel treatment significantly
reduced plasma high-density lipoprotein levels and increased plasma hydroperoxide
levels when compared to breast cancer patients without chemotherapy. Furthermore,
augmented C-reactive protein and creatine kinase fraction MB were found to be
significantly higher in paclitaxel-treated patients in comparison with healthy
controls. CONCLUSIONS: Taken together, these data suggest that a single dose of
short paclitaxel infusion is sufficient to trigger significant alterations in
lipid metabolism, which puts breast cancer patients at risk for increased
incidence of cardiovascular disease.
PMID- 28689297
TI - Estrogen protects both sexes against EAE by promoting common regulatory cell
subtypes independent of endogenous estrogen.
AB - Autoimmune diseases including multiple sclerosis predominantly affect females.
Although high levels of sex hormones, particularly estrogen (E2), can reduce
proinflammatory immune responses, it remains unclear if a lack of endogenous sex
hormones might affect treatment with exogenous sex hormones. Pretreatment with E2
almost completely prevents intact female and male mice from developing clinical
and histological signs of experimental autoimmune encephalomyelitis (EAE) by
promoting various regulatory immune cell phenotypes. To evaluate the effects of
exogenous estrogen in the absence of endogenous sex hormones, the current study
compared EAE severity and the emergence of different immunoregulatory cell
populations after E2 pretreatment of ovariectomized (OVX) female versus male
mice. We found that E2 equally protected both OVX females and males from EAE over
a 21 day observation period concomitant with reduced total cell numbers in spleen
and spinal cord (males only), but enhanced percentages of CD19+CD5+CD1dhi,
CD19+CD138+CD44hi and CD19+Tim-1+ Breg cells, CD8+CD122+ Treg cells and CD11b+CD
206+ARG-1+ anti-inflammatory M2-like monocytes/macrophages in both groups. In
contrast, E2 decreased the percentage of CD4+CD25+FoxP3+ Treg cells in OVX
females but increased these Treg cells in males and intact female mice. These
data suggest that with the exception of CD4+CD25+FoxP3+ Treg cells, E2 protection
against EAE promotes highly overlapping immunoregulatory subsets in OVX females
and males.
PMID- 28689299
TI - 4-O'-methylhonokiol protects from alcohol/carbon tetrachloride-induced liver
injury in mice.
AB - : Alcoholic liver disease (ALD) is a leading cause of liver cirrhosis, liver
cancer, and related mortality. The endocannabinoid system contributes to the
development of chronic liver diseases, where cannabinoid receptor 2 (CB2) has
been shown to have a protecting role. Thus, here, we investigated how CB2 agonism
by 4'-O-methylhonokiol (MHK), a biphenyl from Magnolia grandiflora, affects
chronic alcohol-induced liver fibrosis and damage in mice. A combination of
alcohol (10% vol/vol) and CCl4 (1 ml/kg) was applied to C57BL/6 mice for 5 weeks.
MHK (5 mg/kg) was administered daily, and liver damage assessed by serum AST and
ALT levels, histology, gene, and protein expression. Endocannabinoids (ECs) and
related lipid derivatives were measured by liquid chromatography and mass
spectrometry (LC-MS) in liver tissues. In vitro, MHK was studied in TGFbeta1
activated hepatic stellate cells (HSC). MHK treatment alleviated hepatic
fibrosis, paralleled by induced expression of matrix metalloproteinases (MMP)-2,
3, -9, and -13, and downregulation of CB1 mRNA. Necrotic lesions and hepatic
inflammation were moderately improved, while IL-10 mRNA increased and IFNgamma,
Mcl-1, JNK1, and RIPK1 normalized by MHK. Hepatic anandamide (AEA) and related N
acetylethanolamines (NAEs) were elevated in MHK group, whereas fatty acid
synthase and diacylglycerol O-acyltransferase 2 expression reduced. In vitro, MHK
prevented HSC activation and induced apoptosis via induction of bak1 and bcl-2.
To conclude, MHK revealed hepatoprotective effects during alcohol-induced liver
damage through the induction of MMPs, AEA, and NAEs and prevention of HSC
activation, indicating MHK as a potent therapeutic for liver fibrosis and ALD.
KEY MESSAGES: Methylhonokiol improves liver damage and survival. Methylhonokiol
reduces hepatic fibrosis and necroinflammation. Methylhonokiol prevents
myofibroblast activation and induces apoptosis. Methylhonokiol upregulates
endocannabinoids and related N-acylethanolamines. Methylhonokiol contributes to
lipid hydrolysis via PPARalpha/gamma.
PMID- 28689301
TI - Ethanol production from sweet sorghum bagasse through process optimization using
response surface methodology.
AB - In this study, comparative evaluation of acid- and alkali pretreatment of sweet
sorghum bagasse (SSB) was carried out for sugar production after enzymatic
hydrolysis. Results indicated that enzymatic hydrolysis of alkali-pretreated SSB
resulted in higher production of glucose, xylose and arabinose, compared to the
other alkali concentrations and also acid-pretreated biomass. Response Surface
Methodology (RSM) was, therefore, used to optimize parameters, such as alkali
concentration, temperature and time of pretreatment prior to enzymatic hydrolysis
to maximize the production of sugars. The independent variables used during RSM
included alkali concentration (1.5-4%), pretreatment temperature (125-140
degrees C) and pretreatment time (10-30 min) were investigated. Process
optimization resulted in glucose and xylose concentration of 57.24 and 10.14 g/L,
respectively. Subsequently, second stage optimization was conducted using RSM for
optimizing parameters for enzymatic hydrolysis, which included substrate
concentration (10-15%), incubation time (24-60 h), incubation temperature (40-60
degrees C) and Celluclast concentration (10-20 IU/g-dwt). Substrate concentration
15%, (w/v) temperature of 60 degrees C, Celluclast concentration of 20 IU/g-dwt
and incubation time of 58 h led to a glucose concentration of 68.58 g/l. Finally,
simultaneous saccharification fermentation (SSF) as well as separated hydrolysis
and fermentation (SHF) was evaluated using Pichia kudriavzevii HOP-1 for
production of ethanol. Significant difference in ethanol concentration was not
found using either SSF or SHF; however, ethanol productivity was higher in case
of SSF, compared to SHF. This study has established a platform for conducting
scale-up studies using the optimized process parameters.
PMID- 28689300
TI - Apoptotic and genotoxic effects of low-intensity ultrasound on healthy and
leukemic human peripheral mononuclear blood cells.
AB - PURPOSE: To scrutinize the apoptotic and genotoxic effects of low-intensity
ultrasound and an ultrasound contrast agent (SonoVue; Bracco Diagnostics Inc.,
EU) on human peripheral mononuclear blood cells (PMBCs). METHODS: PMBCs were
subjected to a low-intensity ultrasound field (1-MHz frequency; spatial peak
temporal average intensity 0.18 W/cm2) followed by analysis for apoptosis and DNA
damage (single-strand breaks + double-strand breaks). The comet assay was then
repeated after 2 h to examine the ability of cells to repair DNA breaks. RESULTS:
The results demonstrated that low-intensity ultrasound was capable of selectively
inducing apoptosis in leukemic PMBCs, but not in healthy cells. The introduction
of ultrasound contrast agent SonoVue resulted in an increase in apoptosis in both
groups. DNA analysis after ultrasound exposure indicated that ultrasound
triggered DNA damage in leukemic PMBCs (66.05 +/- 13.36%), while the damage was
minimal (7.01 +/- 0.89%) in control PMBCs. However, both cell lines demonstrated
an ability to repair DNA single- and double-strand breaks 2 h after sonication.
CONCLUSIONS: The study demonstrated that low-intensity ultrasound selectively
induced apoptosis in cancer PMBCs. Ultrasound-induced DNA damage was observed
primarily in leukemic PMBCs. Nevertheless, both cell lines were able to repair
ultrasound-mediated DNA strand breaks.
PMID- 28689302
TI - Ligand-Directed Signaling at the Delta Opioid Receptor.
AB - Delta opioid receptors (deltaORs) regulate a number of physiological functions,
and agonists for this receptor are being pursued for the treatment of mood
disorders, chronic pain, and migraine. A major challenge to the development of
these compounds is that, like many G-protein coupled receptors (GPCRs), agonists
at the deltaOR can induce very different signaling and receptor trafficking
events. This concept, known as ligand-directed signaling, functional selectivity,
or biased agonism, can result in different agonists producing highly distinct
behavioral consequences. In this chapter, we highlight the in vitro and in vivo
evidence for ligand-directed signaling and trafficking at the deltaOR. A number
of biological implications of agonist-directed signaling at the deltaOR have been
demonstrated. Importantly, ligand-specific effects can impact both acute
behavioral effects of delta agonists, as well as the long-term adaptations
induced by chronic drug treatment. A better understanding of the specific
signaling cascades that regulate these differential behavioral effects would help
to guide rational drug design, ultimately resulting in deltaOR agonists with
fewer adverse effects.
PMID- 28689304
TI - Effect of dietary inclusion of graded levels of toasted guar meal on performance,
nutrient digestibility, carcass traits, and serum parameters in commercial
broiler chickens.
AB - An experiment was conducted in a completely randomized design to explore the
replacement value of toasted guar meal (TGM) for soybean meal (SBM) in commercial
broiler diets. Hypothesis was tested by including graded levels (0, 6, 9, 12, 15,
and 18% of diet) of TGM to replace maize-SBM on growth performance, apparent
nutrient digestibility, carcass traits, and serum parameters. A total of six iso
nitrogenous and iso-caloric diets were prepared, and each diet was fed ad libitum
to 12 replicates of five chicks each from 1 to 42 days of age. Results showed
that inclusion of TGM up to 12% in broiler diets did not affect the body weight
gain, feed efficiency, and energy digestibility. Feed intake, dry matter,
nitrogen digestibility, and relative weights of ready-to-cook yields, breast
muscle, abdominal fat, liver, and pancreas were not affected (P > 0.05) by
incorporating TGM even up to 18% in broiler diets. Concentration of glucose,
total protein, and triglyceride in serum was also not affected (P > 0.05), while
serum total cholesterol concentration was found to be higher (P < 0.05) in
broilers fed diets containing TGM as compared to those fed on 0% TGM diet. From
the results, it was evident that TGM may be incorporated up to 12% in commercial
broiler diets for better growth performance, nutrient digestibility, and carcass
traits.
PMID- 28689303
TI - Direct calorimetry: a brief historical review of its use in the study of human
metabolism and thermoregulation.
AB - Direct calorimetry is the gold standard means of measuring human metabolic rate
and its use has been fundamental for understanding metabolism in health and
disease. While metabolic rate is now more commonly estimated indirectly from
measures of the oxygen consumed during respiration, direct calorimetry provides
the user with the unique capacity to quantify the heat produced from aerobic and
anaerobic metabolism by measuring heat exchange between the body and the
environment. This review provides a brief historical overview of the fundamental
concepts which underlie direct calorimetry, of pioneer scientists which developed
these concepts into functional pieces of equipment and the subsequent use of
direct calorimetry to advance our understanding of energy balance, nutrition, and
the pathogenesis of metabolic diseases. Attention is directed to seminal studies
that successfully employed direct calorimetry to verify that the law of energy
conservation also applies to human beings and to establish the validity of
indirect calorimetry. Finally, we discuss the more recent use of direct
calorimetry for the measurement of whole-body heat exchange and body heat storage
in the study of human thermoregulation.
PMID- 28689305
TI - Assessment of drug-related problems in pediatric ward of Zewditu Memorial
Referral Hospital, Addis Ababa, Ethiopia.
AB - Background Although medications play a vital role in the cure, palliation, and
inhibition of disease, they also expose patients to drug-related problems (DRPs).
DRPs are common in hospitalized patients. Specifically, pediatrics population are
easily affected by DRPs, as dynamic and kinetic behaviors of drugs in this
population are usually different than in adults. Objectives To assess the
prevalence of DRPs and associated factors in a pediatric setting in Ethiopia.
Setting Pediatric ward of Zewditu Memorial Referral Hospital, Addis Abbeba,
Ethiopia. Methods A cross-sectional study was conducted on 285 randomly selected
patients. Data were obtained through review of physician medication orders and
patient files. The prevalence and type of DRPs were studied and documented using
the Pharmaceutical Care Network Europe Foundation classification system. The
results were summarized using descriptive statistics including frequency, mean,
and standard deviation. To identify the independent predicators of DRPs, logistic
regression analysis was run and a P value <=0.05 was considered as statistically
significant. Main outcome measure DRPs, types of DRPs, drugs that are frequently
involved in DRPs, and factors associated with DRPs. Main outcome measure Number
of DRPs. Results Of the 1055 medication orders reviewed, a total of 106 DRPs were
identified in 90 patients. This gives an overall rate of drug-related problems of
31.57%. The most frequently identified DRPs were dosing problems, with dose too
low being 34.9% and dose too high being 7.5%. This was followed by drug-drug
interactions (38.67%) and adverse drug reactions (8.49%). The number of
prescribed drugs (AOR 2.3, 95% CI 1.3-4.3, P = 0.007) and total number of disease
conditions (AOR 4.8, 95% CI 1.9, 12.1, P = 0.001) were potential risk factors for
occurrence of DRPs. Conclusion The present study demonstrated that DRPs were
common at the pediatric ward of Zewditu Memorial Referral Hospital and that it
needs great attention. The most frequently identified DRPs were dosing problems,
followed by drug-drug interactions and adverse drug reaction. Poly-pharmacy and
number of disease conditions have been identified as important risk factors for
occurrence of DRPs. The investigators recommend establishing a system for
reporting DRPs in the pediatric ward of the hospital as it may facilitate
appropriate measures for prospective interventions, such as training the
healthcare team, as well as detail precautions to be followed by the
practitioners. In addition to this, improving communication between the
healthcare team members such as physicians, pharmacists, nurses, and other
healthcare workers in the hospital is recommended.
PMID- 28689306
TI - Targeted spine strengthening exercise and posture training program to reduce
hyperkyphosis in older adults: results from the study of hyperkyphosis, exercise,
and function (SHEAF) randomized controlled trial.
AB - : A 6-month randomized controlled trial of spine-strengthening exercise and
posture training reduced both radiographic and clinical measures of kyphosis.
Participants receiving the intervention improved self-image and satisfaction with
their appearance. Results suggest that spine-strengthening exercise and postural
training may be an effective treatment option for older adults with
hyperkyphosis. INTRODUCTION: The purpose of the present study is to determine in
a randomized controlled trial whether spine-strengthening exercises improve Cobb
angle of kyphosis in community-dwelling older adults. METHODS: We recruited
adults >=60 years with kyphosis >=40 degrees and enrolled 99 participants (71
women, 28 men), mean age 70.6 +/- 0.6 years, range 60-88, with baseline Cobb
angle 57.4 +/- 12.5 degrees . The intervention included group spine-strengthening
exercise and postural training, delivered by a physical therapist, 1-h, three
times weekly for 6 months. Controls received four group health education
meetings. The primary outcome was change in the gold standard Cobb angle of
kyphosis measured from standing lateral spine radiographs. Secondary outcomes
included change in kyphometer-measured kyphosis, physical function (modified
Physical Performance Test, gait speed, Timed Up and Go, Timed Loaded Standing, 6
Min Walk), and health-related quality of life (HRQoL) (PROMIS global health and
physical function indexes, SRS-30 self-image domain). ANCOVA was used to assess
treatment effects on change from baseline to 6 months in all outcomes. RESULTS:
There was a -3.0 degrees (95% CI -5.2, -0.8) between-group difference in change
in Cobb angle, p = 0.009, favoring the intervention and approximating the
magnitude of change from an incident vertebral fracture. Kyphometer-measured
kyphosis (p = 0.03) and SRS-30 self-esteem (p < 0.001) showed favorable between
group differences in change, with no group differences in physical function or
additional HRQoL outcomes, p > 0.05. CONCLUSIONS: Spine-strengthening exercise
and posture training over 6 months reduced kyphosis compared to control. Our
randomized controlled trial results suggest that a targeted kyphosis-specific
exercise program may be an effective treatment option for older adults with
hyperkyphosis. TRIAL REGISTRATION NUMBER AND NAME OF TRIAL REGISTER:
ClinicalTrials.gov; identifier NCT01751685.
PMID- 28689308
TI - Triheptanoin: A Rescue Therapy for Cardiogenic Shock in Carnitine-acylcarnitine
Translocase Deficiency.
AB - Carnitine-acylcarnitine translocase (CACT) deficiency is a rare long-chain fatty
acid oxidation disorder (LC-FAOD) with high mortality due to cardiomyopathy or
lethal arrhythmia. Triheptanoin (UX007), an investigational drug composed of
synthetic medium odd-chain triglycerides, is a novel therapy in development for
LC-FAOD patients. However, cases of its safe and efficacious use to reverse
severe heart failure in CACT deficiency are limited. Here, we present a detailed
report of an infant with CACT deficiency admitted in metabolic crisis that
progressed into severe cardiogenic shock who was successfully treated by
triheptanoin. The child was managed, thereafter, on triheptanoin until her death
at 3 years of age from a cardiopulmonary arrest in the setting of acute
respiratory illness superimposed on chronic hypercarbic respiratory failure.
PMID- 28689307
TI - Long-term follow-up in osteogenesis imperfecta type VI.
AB - : This retrospective study on long-term outcomes in osteogenesis imperfecta type
VI found that patients who received intravenous bisphosphonate treatment had an
increase in lumbar spine areal bone mineral density, a higher final height z
score, and some reshaping of vertebral bodies. INTRODUCTION: Osteogenesis
imperfecta (OI) type VI is an ultra-rare bone fragility disorder caused by
recessive mutations in SERPINF1. Here, we describe long-term outcomes in OI type
VI and compare the clinical phenotypes caused by different types of SERPINF1
mutations. METHODS: This study includes a retrospective chart review of 13
individuals with OI type VI. RESULTS: In the absence of therapy, lumbar spine
areal bone mineral density (BMD) did not increase during childhood and
longitudinal growth seemed to stall after the age of 6 to 8 years. The phenotype
was similar between individuals with different types of SERPINF1 mutations.
Intravenous bisphosphonate treatment was associated with an increase in lumbar
spine areal BMD and some reshaping of compressed vertebral bodies. Patients who
had started bisphosphonate treatment early (before the age of 6 years) were
taller than patients who had received bisphosphonate treatment later during their
growing years. Lower extremity fractures were frequent despite bisphosphonate
treatment and scoliosis was present in all patients who had reached the final
height. Most patients had restricted mobility. In four patients, intravenous
bisphosphonate treatment was eventually substituted by subcutaneous injections of
denosumab, without clear changes in the clinical picture. CONCLUSIONS: Patients
with OI type VI who received intravenous bisphosphonate treatment during growth
had an increase in lumbar spine areal BMD, a higher final height z-score, and
presented some reshaping of vertebral bodies. More effective treatment modalities
are clearly required in OI type VI.
PMID- 28689309
TI - The influence of gender on early adverse events, hospital charges and length of
stay after shoulder arthroplasty.
AB - PURPOSE: To identify differences in demographics, diagnosis, arthroplasty type,
early adverse events, length of stay, and hospital costs between men and women
undergoing shoulder arthroplasty. METHODS: We used a nationally representative
U.S. population database to determine annual rates of shoulder arthroplasty (SA)
in patients (2002-2011). Early adverse events, length-of-stay and hospitalization
costs were determined, and compared between patient genders. RESULTS: A cohort of
372,753 patients underwent total-SA (TSA) (59.7% females). Females were
significantly older, more often had Medicare insurance, had a higher proportion
of fracture diagnosis, more often underwent hemiarthroplasty (HA), and had
significantly lower odds of any adverse event, MI, and sepsis, but higher odds of
peripheral nerve injury. Females had significantly greater hospital lengths of
stay for all combined procedures, and isolated TSA, reverse-TSA, and HA. Hospital
costs were significantly lower in females for all combined procedures and HA.
CONCLUSIONS: Male patients had significantly higher odds of adverse events,
death, MI, and sepsis following SA. Female patients had significantly longer
lengths of stay but lower hospital charges following SA.
PMID- 28689310
TI - An Interactive Mobile Phone-Website Platform to Facilitate Real-Time Management
of Medication in Chronically ill Patients.
AB - Poor adherence to medication is a prevalent issue that affects 50-60% of
chronically ill patients. We present Medplan, a platform for patients/caregivers
and healthcare professionals (HCPs) that aims to enhance adherence, increase
patient medication knowledge, and facilitate communication between patients and
HCPs. The Medplan platform was designed and developed by a multidisciplinary team
composed of primary care and hospital physicians, pharmacists, patients, and
developers. We questioned 62 patients in order to know their opinion about the
different functions the app would incorporate and other possible features that
should be taken into consideration. Medplan comprises a website for HCPs and an
application (app) that is installed on the patient's phone. The app is available
in Spanish, Catalan, and English. The patient's medication plan was introduced by
the HCP and interfaced with the app. Each medicine is represented by an icon
showing the indication of the treatment, the trade name, active ingredients,
dose, and route of administration. Information about special requirements (e.g.,
need to take medication on an empty stomach), side effects, or lifestyle
recommendations can also be provided. Additional functions include a medication
reminder alarm system, by which patients can confirm whether or not they have
taken the drug. Patients can self-track their adherence, and all data collected
are sent automatically to the website for analysis by the HCP. Weekly motivation
messages are sent to encourage adherence. A tool enabling interactive
communication between patients and HCPs (primary care or hospital care) is also
included. The app contains a feature enabling the HCP to verify the suitability
of over-the-counter drugs. Medplan has the potential to significantly improve
management of medication in chronically ill patients. A pilot study is being
conducted to test whether Medplan is useful and effective.
PMID- 28689311
TI - Frequency of familial pituitary adenoma syndromes among patients with functioning
pituitary adenomas in a reference outpatient clinic.
AB - INTRODUCTION: Pituitary adenomas (PA) occur mainly as sporadic disease, but
familial syndromes are found in approximately 5% of cases. Identification of
these syndromes is important in order to diagnose individuals at risk at an
earlier stage. AIMS: To evaluate the frequency of familial PA in a reference
outpatient clinic devoted to PA treatment and to identify family members
suspected to have pituitary disease. METHODS: Patients with PA were interviewed
with respect to the presence of family members with diagnosis of PA or with signs
or symptoms suggestive of them. The family members who had a clinical picture
suggestive of pituitary disease were further evaluated in an attempt to identify
new PA cases. In families with familial disease, the AIP gene was sequenced.
RESULTS: 262 patients were evaluated and familial syndrome was found in 13 (5%).
Ten (3.8%) patients had familial isolated PA (FIPA) and three (1.2%) had multiple
endocrine neoplasia type 1. After evaluation of family members' symptomatology,
110 were considered suspected of having pituitary disease, but only 24
participated in the study. Of these 24, 1 was diagnosed with a corticotropinoma.
AIP mutations were found in 20% of FIPA families. CONCLUSION: We found a
frequency of familial PA similar to that previously described, as well as a
similar frequency of AIP mutations among FIPA families. An active search of the
affected family members was able to identify one case of Cushing's disease.
Patients should be aware of pituitary disease's clinical picture to identify
possibly affected family members.
PMID- 28689312
TI - Sleep, chronotype, and sleep hygiene in children with attention
deficit/hyperactivity disorder, autism spectrum disorder, and controls.
AB - Sleep problems are highly prevalent in ADHD and autism spectrum disorder (ASD).
Better insight in the etiology is of clinical importance since intervention and
prevention strategies of sleep problems are directed at underlying mechanisms. We
evaluated the association of sleep problems and sleep patterns with sleep hygiene
(behavioral/environmental practices that influence sleep quality, e.g. caffeine
use), access to electronic media, chronotype, and anxiety/depression in children
aged 6-12 years with ADHD, ASD, or typical development (TD) using parental
questionnaires. ANOVA and linear regression analyses were adjusted for age and
sex. Children with ADHD and ASD showed more sleep problems (63.6 and 64.7%, vs
25.1% in TD) and shorter sleep duration than controls, while differences between
ADHD and ASD were not significant. Sleep hygiene was worse in ADHD and ASD
compared to TD, however, the association of worse sleep hygiene with more sleep
problems was only significant in ASD and TD. There was a significant association
of access to electronic media with sleep problems only in typically developing
controls. Chronotype did not differ significantly between groups, but evening
types were associated with sleep problems in ADHD and TD. Associations of greater
anxiety/depression with more sleep problems were shown in ADHD and TD; however,
anxiety/depression did not moderate the effects of chronotype and sleep hygiene.
We conclude that sleep problems are highly prevalent in ADHD and ASD, but are
differentially related to chronotype and sleep hygiene. In ASD, sleep problems
are related to inadequate sleep hygiene and in ADHD to evening chronotype, while
in TD both factors are important. Clinical implications are discussed.
PMID- 28689313
TI - 137Cs transmission imaging and segmented attenuation corrections in a small
animal PET scanner.
AB - Attenuation correction (AC) is required for accurate quantitative evaluation of
small animal PET data. Our objective was to compare three AC methods in the small
animal Clairvivo-PET scanner. The three AC methods involve applying attenuation
coefficient maps generated by simulating a cylindrical map (SAC), segmenting the
emission data (ESAC), and segmenting the transmission data (TSAC), imaged using a
137Cs single-photon source. Investigation was carried out using a 65 mm uniform
cylinder and an NEMA NU4 2008 mouse phantom, filled with water or tungsten
liquid, to mimic bone. Evaluation was carried out using the difference of the
segmented map volume from the known cylindrical phantom volume, the recovery of
the radioactivity concentration, and the line profiles. The optimal transmission
scan time for achieving accurate AC using TSAC was determined using 5, 10, 15,
20, and 25 min transmission scan time. The effects of scatter correction and
reconstruction algorithms on ESAC were investigated. SAC showed the best
performance but was unable to correct for different tissues and the scanner bed,
and faced difficulty with correct positioning of the attenuation coefficient map.
ESAC was affected by scatter correction and reconstruction algorithm, and may
result in poor boundary delineation, and hence was unreliable. TSAC showed
reasonable performance but required further optimization of the default
segmentation setting. A minimum transmission scan time of 20 min is recommended
for Clairvivo-PET using 137Cs source to ensure that sufficient transmission
counts are obtained to generate accurate attenuation coefficient map.
PMID- 28689314
TI - Overview of deep learning in medical imaging.
AB - The use of machine learning (ML) has been increasing rapidly in the medical
imaging field, including computer-aided diagnosis (CAD), radiomics, and medical
image analysis. Recently, an ML area called deep learning emerged in the computer
vision field and became very popular in many fields. It started from an event in
late 2012, when a deep-learning approach based on a convolutional neural network
(CNN) won an overwhelming victory in the best-known worldwide computer vision
competition, ImageNet Classification. Since then, researchers in virtually all
fields, including medical imaging, have started actively participating in the
explosively growing field of deep learning. In this paper, the area of deep
learning in medical imaging is overviewed, including (1) what was changed in
machine learning before and after the introduction of deep learning, (2) what is
the source of the power of deep learning, (3) two major deep-learning models: a
massive-training artificial neural network (MTANN) and a convolutional neural
network (CNN), (4) similarities and differences between the two models, and (5)
their applications to medical imaging. This review shows that ML with feature
input (or feature-based ML) was dominant before the introduction of deep
learning, and that the major and essential difference between ML before and after
deep learning is the learning of image data directly without object segmentation
or feature extraction; thus, it is the source of the power of deep learning,
although the depth of the model is an important attribute. The class of ML with
image input (or image-based ML) including deep learning has a long history, but
recently gained popularity due to the use of the new terminology, deep learning.
There are two major models in this class of ML in medical imaging, MTANN and CNN,
which have similarities as well as several differences. In our experience, MTANNs
were substantially more efficient in their development, had a higher performance,
and required a lesser number of training cases than did CNNs. "Deep learning", or
ML with image input, in medical imaging is an explosively growing, promising
field. It is expected that ML with image input will be the mainstream area in the
field of medical imaging in the next few decades.
PMID- 28689315
TI - Enantiomer-Selective Photo-Induced Reaction of Protonated Tryptophan with
Disaccharides in the Gas Phase.
AB - In order to investigate chemical evolution in interstellar molecular clouds,
enantiomer-selective photo-induced chemical reactions between an amino acid and
disaccharides in the gas phase were examined using a tandem mass spectrometer
containing an electrospray ionization source and a cold ion trap. Ultraviolet
photodissociation mass spectra of cold gas-phase noncovalent complexes of
protonated tryptophan (Trp) enantiomers with disaccharides consisting of two D
glucose units, such as D-maltose or D-cellobiose, were obtained by
photoexcitation of the indole ring of Trp. NH2CHCOOH loss via cleavage of the
Calpha-Cbeta bond in Trp induced by hydrogen atom transfer from the NH3+ group of
a protonated Trp was observed in a noncovalent heterochiral H+(L-Trp)(D-maltose)
complex. In contrast, a photo-induced chemical reaction forming the product ion
with m/z 282 occurs in homochiral H+(D-Trp)(D-maltose). For D-cellobiose, both
NH2CHCOOH elimination and the m/z 282 product ion were observed, and no
enantiomer-selective phenomena occurred. The m/z 282 product ion indicates that
the photo-induced C-glycosylation, which links D-glucose residues to the indole
moiety of Trp via a C-C bond, can occur in cold gas-phase noncovalent complexes,
and its enantiomer-selectivity depends on the structure of the disaccharide.
PMID- 28689316
TI - Higher Lipophilic Index Indicates Higher Risk of Coronary Heart Disease in
Postmenopausal Women.
AB - Fatty acids (FAs) are essential components of cell membranes and play an integral
role in membrane fluidity. The lipophilic index [LI, defined as the sum of the
products between FA levels and melting points ( degrees C), divided by the total
amount of FA: [Formula: see text]] is thought to reflect membrane and lipoprotein
fluidity and may be associated with the risk of coronary heart disease (CHD).
Therefore, we examined the associations of dietary and plasma phospholipid (PL)
LI with CHD risk among postmenopausal women. We determined dietary LI for the
cohort with completed baseline food frequency questionnaires and free of
prevalent cardiovascular diseases in the Women's Health Initiative (WHI)
observational study (N = 85,563). We additionally determined plasma PL LI in a
matched case-control study (N = 2428) nested within the WHI observational cohort
study. Cox proportional hazard regression and multivariable conditional logistic
regression were used to calculate HRs/ORs for CHD risk between quartiles of LI
after adjusting for potential sources of confounding and selection bias. Higher
dietary LI in the cohort study and plasma PL LI in the case-control study were
significantly associated with increased risk of CHD: HR = 1.18 (95% CI 1.07-1.31,
P for trend <0.01) and OR = 1.76 (95% CI 1.33-2.33, P for trend <0.01) comparing
extreme quartiles and adjusting for potential confounders. These associations
still persisted after adjusting for the polyunsaturated to saturated fat ratio.
Our study indicated that higher LI based on either dietary or plasma
measurements, representing higher FA lipophilicity, was associated with elevated
risk of CHD among postmenopausal women.
PMID- 28689317
TI - Intentional binding of two effects.
AB - An action that produced an effect is perceived later in time compared to an
action that did not produce an effect. Likewise, the effect of an action is
perceived earlier in time compared to a stimulus that was not produced by an
action. Despite numerous studies on this phenomenon-referred to as Intentional
Binding effect (IB)-the underlying mechanisms are still not fully understood.
Typically, IB is investigated in settings where the action produces just one
single effect, whereas in everyday action contexts, it rather causes a sequence
of effects before leading to the desired outcome. Therefore, we investigated IB
of two consecutive effects. We observed substantially more IB of a first effect
tone compared to a second tone. This pattern was observed for second tones that
were temporally predictable (Exp. 1) or not (Exp. 2 and 3). Interestingly, the
second tone yielded stronger IB when it was less delayed (Exp. 4). Thus, also an
event occurring later in an unfolding action-effect sequence can be bound to its
causing action, but it might be less bound to the action than a first effect.
Instead of the fact that it is the second of two consecutive effects, this,
however, rather seems to be influenced by the longer delay of a second and,
therefore, later occurring effect.
PMID- 28689318
TI - Destination memory: the relationship between memory and social cognition.
AB - Destination memory refers to the ability to remember to whom one has sent
information (e.g., "did I tell my colleague X or Y about the conference?", "did I
send that email to my colleague X or Y?"). This review describes empirical
studies demonstrating how normal aging and neurological disorders compromise
destination memory. Centrally, we propose a comprehensive framework, destination
memory framework (DMF), in which destination memory contributes to the uniqueness
of a communications episode by creating an association between the content of a
communications event and the context of its transmission. The DMF also focuses on
how the association between communicated information and its destination, an
association mainly supported by binding, can be related to the subjective
experience of an episode. Additionally, the DMF emphasizes how destination recall
can be influenced by social processing, specifically by familiarity of
interlocutors, stereotypes that are associated with interlocutors, and the
perceived emotional and cognitive states of interlocutors. By so doing, we
highlight how destination memory can be intertwined with not only basic cognition
but social cognition as well.
PMID- 28689319
TI - Barriers to success: physical separation optimizes event-file retrieval in shared
workspaces.
AB - Sharing tasks with other persons can simplify our work and life, but seeing and
hearing other people's actions may also be very distracting. The joint Simon
effect (JSE) is a standard measure of referential response coding when two
persons share a Simon task. Sequential modulations of the joint Simon effect
(smJSE) are interpreted as a measure of event-file processing containing stimulus
information, response information and information about the just relevant control
state active in a given social situation. This study tested effects of physical
(Experiment 1) and virtual (Experiment 2) separation of shared workspaces on
referential coding and event-file processing using a joint Simon task. In
Experiment 1, participants performed this task in individual (go-nogo), joint and
standard Simon task conditions with and without a transparent curtain (physical
separation) placed along the imagined vertical midline of the monitor. In
Experiment 2, participants performed the same tasks with and without receiving
background music (virtual separation). For response times, physical separation
enhanced event-file retrieval indicated by an enlarged smJSE in the joint Simon
task with curtain than without curtain (Experiment1), but did not change
referential response coding. In line with this, we also found evidence for
enhanced event-file processing through physical separation in the joint Simon
task for error rates. Virtual separation did neither impact event-file
processing, nor referential coding, but generally slowed down response times in
the joint Simon task. For errors, virtual separation hampered event-file
processing in the joint Simon task. For the cognitively more demanding standard
two-choice Simon task, we found music to have a degrading effect on event-file
retrieval for response times. Our findings suggest that adding a physical
separation optimizes event-file processing in shared workspaces, while music
seems to lead to a more relaxed task processing mode under shared task
conditions. In addition, music had an interfering impact on joint error
processing and more generally when dealing with a more complex task in isolation.
PMID- 28689320
TI - Pollutant loading from low-density residential neighborhoods in California.
AB - This paper presents a comparison of pollutant load estimations for runoff from
two geographically distinct residential suburban neighborhoods in northern and
southern California. The two neighborhoods represent a single urban land use
type: low-density residential in small catchments (<0.3 km2) under differing
regional climates and irrigation practices. Pollutant loads of pesticides,
nutrients, and drinking water constituents of concern are estimated for both
storm and non-storm runoff. From continuous flow monitoring, it was found that a
daily cycle of persistent runoff that peaks mid-morning occurs at both sites.
These load estimations indicate that many residential neighborhoods in California
produce significant non-storm pollutant loads year-round. Results suggest that
non-storm flow accounted for 47-69% of total annual runoff and significantly
contributed to annual loading rates of most nutrients and pesticides at both
sites. At the Southern California site, annual non-storm loads are 1.2-10 times
higher than storm loads of all conventional constituents and nutrients with one
exception (total suspended solids). At the Northern California site, annual storm
loads range from 51 to 76% of total loads for all conventional constituents and
nutrients with one exception (total dissolved solids). Non-storm yields of
pesticides at the Southern California site range from 1.3-65 times higher than
those at the Northern California site. The disparity in estimated pollutant loads
between the two sites indicates large potential variation from site-to-site
within the state and suggests neighborhoods in drier and milder climates may
produce significantly larger non-storm loads due to persistent dry season runoff
and year-round pest control.
PMID- 28689321
TI - Underestimated risk of cancer in solitary thyroid nodules >=3 cm reported as
benign.
AB - BACKGROUND: The study aims to assess the risk of cancer in solitary thyroid
nodules >=30 mm in size reported as Bethesda II, and its implications. METHOD:
The clinical records of 202 patients, who underwent thyroid lobectomy for
solitary nodules measuring >=30 mm, reported as Bethesda II on preoperative FNAC
between Jan 2015 and Apr 2016 were reviewed. Data collected included nodule size
and consistency, and final histopathology results. The risk of cancer and the
recommended management according to ATA guidelines were the outcomes of interest.
Comparisons were then made between two size categories: (30-40 mm; n = 72; C1)
and (>40 mm; n = 130; C2), and two nodule consistencies. RESULTS: Mean nodule
size was 43.2 mm (range 30-92). Ninety-five percent were solid and 5% were
predominantly cystic. The risk of cancer was 22.8% (46/202) with no size
threshold, or graded increase in risk observed. Based on biologic behavior, 50%
of cancers were considered clinically significant. Accordingly, the risk of
cancer for which surgery is recommended was 11.4% (23/202). The risk of cancer
requiring total thyroidectomy was 9.4% and was influenced by nodule size (19 vs.
60% in C1 and C2, respectively; p = 0.01). Predominantly cystic nodules had a
greater risk of malignancy compared to predominantly solid nodules even after
adjusting for size (40 vs. 9.9%; p = 0.01 and 40 vs. 12.5%; p = 0.02,
respectively). CONCLUSION: The risk of malignancy in Bethesda II solitary nodules
>=30 mm is considerable implying a need for changing the way these are approached
and refining cytopathology reporting.
PMID- 28689322
TI - Linear stapled gastrojejunostomy results in fewer strictures compared to circular
stapled gastrojejunostomy in laparoscopic gastric bypass surgery.
AB - PURPOSE: Currently, there are two laparoscopic stapling techniques to perform the
gastrojejunostomy in gastric bypass surgery: the linear stapling and circular
stapling techniques. The aim of the study was to compare the two techniques
regarding postoperative morbidity and weight loss at an accredited bariatric
reference center in Switzerland. METHODS: We compared two consecutive cohorts at
a single institution between November 2012 and June 2014 undergoing laparoscopic
gastric bypass surgery. The frequency of complications and weight loss at 1 year
was assessed in 109 patients with the 21-mm circular stapling technique (CSA) and
134 patients with the linear stapling technique (LSA). RESULTS: Postoperative
complications were more frequent in the CSA group with 23.9 versus 4.5% in the
LSA group (p = <0.0001). The main difference was the frequency of strictures,
which occurred in 15.6% in the CSA group versus 0% in the LSA group. As a result,
endoscopic dilation was required at least once in 15 patients. There was no
statistically significant difference in percentage of excessive weight loss (EWL)
in both groups; EWL was 74% in the CSA group and 73% in the LSA group (p = 0.68).
CONCLUSION: Linear stapled laparoscopic gastric bypass had fewer stenotic
strictures with similar weight loss at 1 year compared to circular stapling
technique.
PMID- 28689323
TI - A sensitive colorimetric assay system for nucleic acid detection based on
isothermal signal amplification technology.
AB - Rapid and accurate detection of microRNAs in biological systems is of great
importance. Here, we report the development of a visual colorimetric assay which
possesses the high amplification capabilities and high selectivity of the rolling
circle amplification (RCA) method and the simplicity and convenience of gold
nanoparticles used as a signal indicator. The designed padlock probe recognizes
the target miRNA and is circularized, and then acts as the template to extend the
target miRNA into a long single-stranded nucleotide chain of many tandem repeats
of nucleotide sequences. Next, the RCA product is hybridized with
oligonucleotides tagged onto gold nanoparticles. This interaction leads to the
aggregation of gold nanoparticles, and the color of the system changes from wine
red to dark blue according to the abundance of miRNA. A linear correlation
between fluorescence and target oligonucleotide content was obtained in the range
0.3-300 pM, along with a detection limit of 0.13 pM (n = 7) and a RSD of 3.9% (30
pM, n = 9). The present approach provides a simple, rapid, and accurate visual
colorimetric assay that allows sensitive biodetection and bioanalysis of DNA and
RNA nucleotides of interest in biologically important samples. Graphical abstract
The colorimetric assay system for analyzing target oligonucleotides.
PMID- 28689324
TI - Fast detection of Listeria monocytogenes through a nanohybrid quantum dot
complex.
AB - Listeria monocytogenes is a recognized foodborne pathogen that causes listeriosis
in susceptible consumers. Currently, the detection systems for Listeria in food
detect live and dead bacteria, being the viable microorganisms most relevant for
their ability to cause sickness in the population at risk. For this reason, a new
nanohybrid compound was developed for the optical detection of Listeria that was
based on polyamidoamine dendrimers functionalized with an auxotrophic cofactor
(lipoic acid), together with the coupling of fluorescent semiconductor crystals
(quantum dots). The nanohybrid sensor has a detection limit for viable L.
monocytogenes of 5.19 * 103 colony-forming units per milliliter under
epifluorescence microscopy. It was specific when used among other pathogens
commonly found in food.
PMID- 28689325
TI - Factors affecting separation and detection of bile acids by liquid chromatography
coupled with mass spectrometry in negative mode.
AB - Bile acids (BAs) are cholesterol metabolites with important biological functions.
They undergo extensive host-gut microbial co-metabolisms during the enterohepatic
circulation, creating a vast structural diversity and resulting in great
challenges to separate and detect them. Based on the bioanalytical reports in the
past decade, this work developed three chromatographic gradient methods to
separate a total of 48 BA standards on an ethylene-bridged hybrid (BEH) C18
column and high-strength silica (HSS) T3 column and accordingly unraveled the
factors affecting the separation and detection of them by liquid chromatography
coupled with mass spectrometry (LC-MS). It was shown that both the acidity and
ammonium levels in mobile phases reduced the electrospray ionization (ESI) of BAs
as anions of [M-H]-, especially for those unconjugated ones without 12
hydroxylation. It was also found that the retention of taurine conjugates on the
BEH C18 column was sensitive to the strength of formic acid and ammonium in
mobile phases. By using the volatile buffers with an equivalent ammonium level as
mobile phases, we comprehensively demonstrated the effects of the elution pH
value on the retention behaviors of BAs on both the BEH C18 column and HSS T3
column. Based on the retention data acquired on a C18 column, we presented the
ionization constants (pK a) of various BAs with the widest coverage beyond those
of previous reports. When we made attempts to establish the structure-retention
relationships (SRRs) of BAs, the lack of discriminative structural descriptors
for BA stereoisomers emerged as the bottleneck problem. The methods and results
presented in this work are especially useful for the development of reliable,
sensitive, high-throughput, and robust LC-MS bioanalytical protocols for the
quantitative metabolomic studies. Graphical Abstract Nonlinear curve fitting of
capacity factors and elution pH value for the separation of common unconjugated
bile acids.
PMID- 28689326
TI - Occurrence and Distribution of Organophosphate Esters in Surface Soil and Street
Dust from Chongqing, China: Implications for Human Exposure.
AB - In the present study, the occurrence, concentrations, and distribution of
organophosphate esters (OPEs) were studied in surface soil and street dust
samples collected from different sites of Chongqing, a metropolitan city in
western China. Furthermore, nondietary daily intakes (DIs) of OPEs only through
dust ingestion absorption were assessed between toddlers and adults. The ?OPEs
contents ranged from 10.1 to 315 ng/g dw and from 348 to 1369 ng/g dw in surface
soil and street dust samples, respectively, with tris (2-butoxyethyl) phosphate
(TBOEP), the predominant OPEs in surface soil, whereas tris (chloroethyl)
phosphate (TCEP) occupied a relatively high proportion in street dust samples.
The mobility of TCEP and tris (2-chloroisopropyl) phosphate (TCIPP) to deeper
soil zones with seepage water may play a role in decreasing contents of both
compounds in surface soil. Considerably different patterns of pairwise
correlations of six OPEs congeners were observed between surface soil and street
dust, which could largely relate to the complicated environmental process for
tris (1,3-dichloroisopropyl) phosphate (TDCIPP) and TCIPP in surface soil.
Analogous sources between surface soil and street dust have been identified
through principal component analysis. Compared with adults, the toddlers were
more vulnerable to OPEs intake, according to the estimated DI values. For both
toddler and adult groups, the estimated exposure values for all OPEs were several
orders of magnitude lower than the reference dose (RfD), not suggesting the
potential risk to human health.
PMID- 28689327
TI - In Utero Evidence of Impaired Somatic Growth in Hypoplastic Left Heart Syndrome.
AB - We hypothesized that fetuses with hypoplastic left heart syndrome (HLHS) have
impaired growth compared to expected growth for gestational age. This is a
retrospective cohort study including singleton fetuses with isolated HLHS
identified from a single, referral center's ultrasound database. To account for
variable timing of ultrasounds, z-scores for gestational age were assigned for
each biometric parameter. We identified 169 fetuses, of which 96 had more than
one ultrasound. The median number of ultrasound evaluations per fetus was 2
(range 1-5). The mean gestational age at time of last ultrasound was 33.7 +/- 4.3
weeks with a range of 20.4-39.6 weeks. While fetal growth restriction (11%) and
microcephaly (3%) were relatively rare, mean z-scores at the time of last
ultrasound for estimated fetal weight (mean difference z-score -0.20, p = 0.04)
and head circumference (-0.28, p = 0.02) were lower than at the time of the
initial ultrasound. Impaired somatic growth, defined as a decrement in z-score of
0.5 or more over time, was common (32%). There is a deceleration in somatic and
head growth in fetuses with hypoplastic left heart syndrome that can be
identified by routine ultrasound evaluation.
PMID- 28689328
TI - Image Quality of Coronary Arteries on Non-electrocardiography-gated High-Pitch
Dual-Source Computed Tomography in Children with Congenital Heart Disease.
AB - This study aimed to evaluate image quality of coronary artery imaging on non
electrocardiography (ECG)-gated high-pitch dual-source computed tomography (DSCT)
in children with congenital heart disease (CHD) and to assess factors affecting
image quality. We retrospectively reviewed the records of 142 children with CHD
who underwent non-ECG-gated high-pitch DSCT. The subjective image quality of the
proximal coronary segments was graded using a five-point scale. A score <3
represented a non-diagnostic image. Age, body weight, and heart rate were
compared between the two groups: patients with good diagnostic image quality in
all four segments and patients with at least one segment with non-diagnostic
image quality. Predictors of image quality were assessed by multivariate logistic
regression, including age, body weight, and heart rate. Four-hundred-fifty-seven
of the 568 segments (80.5%) had diagnostic image quality. Patients with non
diagnostic segments were significantly younger (21.6 +/- 25.5 months), had lower
body weight (7.82 +/- 5.00 kg), and a faster heart rate (123 +/- 23.7 beats/min)
(each p < 0.05) than patients with diagnostic image quality in all four segments
(30.6 +/- 20.7 months, 10.3 +/- 4.00 kg, and 113 +/- 21.6 beats/min,
respectively; each p < 0.05). The multivariate logistic regression revealed that
body weight (odds ratio 1.228; p = 0.029) was a significant predictor of image
quality. Non-ECG-gated high-pitch DSCT provided adequate image quality of the
proximal coronary segments in children with CHD. Lower body weight was a factor
that led to poorer image quality of the coronary arteries.
PMID- 28689329
TI - Amygdala Volume Differences in Autism Spectrum Disorder Are Related to Anxiety.
AB - Recent studies suggest that longstanding findings of abnormal amygdala morphology
in ASD may be related to symptoms of anxiety. To test this hypothesis, fifty
three children with ASD (mean age = 11.9) underwent structural MRI and were
divided into subgroups to compare those with at least one anxiety disorder
diagnosis (n = 29) to those without (n = 24) and to a typically developing
control group (TDC; n = 37). Groups were matched on age and intellectual level.
The ASD and anxiety group showed decreased right amygdala volume (controlled for
total brain volume) relative to ASD without anxiety (p = .04) and TDCs (p =
.068). Results suggest that youth with ASD and co-occurring anxiety have a
distinct neurodevelopmental trajectory.
PMID- 28689330
TI - Phenotypic Characteristics of Autism Spectrum Disorder in a Diverse Sample of
Somali and Other Children.
AB - The potential for culture to impact diagnosis of autism spectrum disorder (ASD)
is high, yet remains largely unstudied. This study examined differences across
racial/ethnic groups in ASD symptoms, cognitive and adaptive skills, and related
behaviors in children with ASD that included a unique subgroup, children from the
Somali diaspora. Somali children were more likely to have ASD with intellectual
disability than children from all other racial/ethnic groups. Few differences
were found in the presence of specific symptoms and behaviors across groups once
IQ was controlled. Results lend support to previous studies that found higher
rates of ASD intellectual disability in children of immigrants from low human
resource index countries compared to other groups. Implications for future
research are discussed.
PMID- 28689331
TI - Pathophysiology and Current Clinical Management of Preeclampsia.
AB - Preeclampsia is characterized by blood pressure greater than 140/90 mmHg in the
second half of pregnancy. This disease is a major contributor to preterm and low
birth weight babies. The early delivery of the baby, which becomes necessary for
maintaining maternal well-being, makes preeclampsia the leading cause for preterm
labor and infant mortality and morbidity. Currently, there is no cure for this
pregnancy disorder. The current clinical management of PE is hydralazine with
labetalol and magnesium sulfate to slow disease progression and prevent maternal
seizure, and hopefully prolong the pregnancy. This review will highlight factors
implicated in the pathophysiology of preeclampsia and current treatments for the
management of this disease.
PMID- 28689332
TI - Sex-specific incidence of EGFR mutation and its association with age and obesity
in lung adenocarcinomas: a retrospective analysis.
AB - PURPOSE: Age and obesity are well-known risk factors for various cancers, but the
potential roles of age and obesity in lung cancer, especially in those with
activating EGFR mutations, have not been thoroughly evaluated. The aim of this
retrospective study is to evaluate the associations between the sex-specific
incidence of EGFR mutations and age and obesity. METHODS: We conducted a
retrospective study based on the data from 1378 lung adenocarcinoma cases. The
degree of obesity was categorized by body mass index (BMI). The associations
between EGFR mutational status and clinical factors, including stage, smoking
history, age group (<=45 years, 46-55, 56-65 and >65), and BMI group (<18.5
kg/m2, 18.5-22.9, 23.0-24.9 and >=25.0) were analyzed using logistic regression
models for each sex. RESULTS: In men, the incidence of EGFR mutation was
inversely associated with age (adjusted odds ratio [OR] for age group = 0.76, p
trend = 0.003) and positively associated with obesity (adjusted OR for BMI group
= 1.23, p-trend = 0.04). In contrast, in women, the incidence of EGFR mutation
was positively associated with age (adjusted OR for age group = 1.19, p-trend =
0.02). However, the incidence of EGFR mutation was not statistically associated
with obesity (adjusted OR for BMI group = 1.03, p-trend = 0.76). CONCLUSIONS: Our
data suggests that age and obesity may contribute to the sex-specific incidence
of EGFR mutation in lung adenocarcinoma in different manners.
PMID- 28689333
TI - The Ribavirin Pregnancy Registry: An Interim Analysis of Potential Teratogenicity
at the Mid-Point of Enrollment.
AB - INTRODUCTION: Significant teratogenic effects have been demonstrated in all
animal species exposed to ribavirin. Ribavirin is prescribed for chronic
hepatitis C and is contraindicated in women who are pregnant and in the male
sexual partners of women who are pregnant. Both sexes are advised to avoid
pregnancy for 6 months after exposure. The Ribavirin Pregnancy Registry was
established in 2003 to monitor pregnancy exposures to ribavirin for signals of
possible human teratogenicity. METHODS: This voluntary registry enrolls pregnant
women with prenatal exposure to ribavirin. Exposure is classified as direct-women
taking ribavirin during pregnancy or the 6 months prior to conception-or indirect
women exposed through sexual contact, 6 months prior to or during pregnancy, with
a man who is taking or has taken ribavirin in the past 6 months. Women are
followed until delivery and infants for 1 year. When enrollment is complete,
birth defect rates will be compared with the Metropolitan Atlanta Congenital
Defects Program's published rate of 2.67. Using data collected since inception in
2003 through February 2016, preliminary rates were calculated. RESULTS: The
registry has enrolled 272 pregnant women, with 180 live births: there were seven
birth defect cases among 85 directly exposed women [7/85 (8.2%) (95% confidence
interval (CI) 3.4-16.2)] and four birth defect cases among 95 indirectly exposed
women [4/95 (4.2%) (95% CI 1.2-10.4)]. Of the 11 infants, nine had structural
defects and two had chromosomal anomalies. Patterns suggesting a common etiology
or relationship with ribavirin exposure are not seen. CONCLUSION: Based on the
patterns of birth defects reported, preliminary findings do not suggest a clear
signal of human teratogenicity for ribavirin. However, the current sample size is
insufficient for definitive conclusions, and ribavirin exposure should be avoided
during pregnancy and during the 6 months prior to pregnancy, in accordance with
prescribing information. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov
identifier: NCT00114712.
PMID- 28689334
TI - Safety and Interactions of Direct Oral Anticoagulants with Antiarrhythmic Drugs.
AB - Direct oral anticoagulants (DOACs) are novel direct-acting medications that are
selective for either thrombin or activated factor X. Due to their obvious
benefits for patients (fewer interactions, broader therapeutic window, etc.),
they are increasingly used as an alternative to warfarin, phenprocoumon, or
acenocoumarol. One of the major indications for use of DOACs is stroke prevention
in patients with atrial fibrillation (AF). However, interactions still exist,
especially in combination with antiarrhythmic drugs (AADs), which are frequently
given to AF patients for rhythm or rate control. These interactions are due to
the cytochrome P450 system and the P-glycoprotein (permeability glycoprotein or
multidrug resistance protein) transport system. For some combinations, dose
reduction of the DOAC is recommended and in some cases contraindications exist.
In addition, impairment in renal and hepatic function plays an important role in
this context. However, compared with pure interactions where data are quite
convincing, the latter topic has been studied only rudimentarily. This review
summarizes the literature on the safety and interactions of AADs when used with
DOACs [dabigatran (a direct inhibitor of factor IIa) and rivaroxaban, apixaban
and edoxaban (direct inhibitors of factor Xa)] and the impact of renal and
hepatic impairment.
PMID- 28689335
TI - An update from the Chair of the students and new professionals Group of the
International Society of Biometeorology.
AB - The Students and New Professionals Group of the International Society of
Biometeorology is composed of approximately 68 members who are either within 5
years from completing graduate studies or under 35 years of age. The group is
represented by 21 countries from around the world and a variety of disciplinary
perspectives working within the area of biometeorology. Here, an update from the
Chair of the Students and New Professionals Group of the International Society of
Biometeorology is provided based on accomplishments and new progress from 2014 to
2017 in advance of the ISB's 60th Anniversary.
PMID- 28689336
TI - V79 Fibroblasts Are Protected Against Reactive Oxygen Species by Flax Fabric.
AB - Chinese hamster pulmonary fibroblasts (V79 cells) pre-treated with flax fabrics
derived from non-modified or genetically engineered flax fibres and treated with
H2O2 revealed a markedly lower level of intracellular reactive oxygen species
(ROS) than control, non-pre-treated cells. The fabrics were prepared from fibres
derived from two kinds of transgenic plants: W92 plants, which overproduce
flavonoids, and M type plants, which produce hydroxybutyrate polymer in their
vascular bundles and thus in fibres. Incubating the V79 cells with the flax
fabrics prior to H2O2 treatment also reduced the amount of DNA damage, as
established using the comet assay (also known as alkaline single-cell gel
electrophoresis) and pulsed-field electrophoresis of intact cellular DNA.
Selected gene expression analysis revealed the activator impact of fabrics on the
apoptotic (BCL2 family, caspases) gene expression. This promoting activity was
also detected for histone acetyltransferase (HAT; MYST2) gene expression. The
flax fabric derived from both GM flax plants exhibited a protective effect
against oxidative stress and ROS-mediated genotoxic damage, but the W92 fabric
was the strongest. It is thus suggested that these fabrics might be useful as a
basis for new biomedical products (e.g. wound dressings) that actively protect
cells against inflammation and degeneration.
PMID- 28689337
TI - Osteoid osteoma of the hand and foot in children successfully treated with
radiofrequency neurotomy probes.
AB - Osteoid osteoma is a common benign tumor that is typically found in young adults
and children, usually in the long bones of the lower extremity. Radiofrequency
ablation (RFA) under computed tomography guidance is the standard of care for
symptomatic osteoid osteomas. However, patients with osteoid osteoma of the hand
or foot are often treated with open surgery because of the risk of injury to
vascular and neural structures from RFA. This risk is more pronounced in
pediatric patients because of the small lesion size and proximity of lesions to
important neurovascular structures. Here, we present 2 pediatric patients, one
with an osteoid osteoma in the hand and the other with an osteoid osteoma in the
foot. In both patients, a 22-gauge, 2.5-mm active tip ablation probe was used.
The smaller ablation volume achieved with this probe protected neighboring
neurovascular structures while effectively ablating the osteoid osteoma nidus.
Based on our success in these cases, we recommend the application of this method
for cases in which neurovascular proximity to the osteoid osteoma lesion makes
ablation challenging.
PMID- 28689338
TI - Synovial sarcoma mimicking benign peripheral nerve sheath tumor.
AB - OBJECTIVE: To assess the radiographic and clinicopathologic features of synovial
sarcoma of the nerve that were clinically or radiologically interpreted as benign
peripheral nerve sheath tumor. MATERIALS AND METHODS: Five patients with synovial
sarcoma arising from the peripheral nerve and interpreted clinically and
radiologically as peripheral nerve sheath tumors were identified.
Clinicopathologic and imaging features were evaluated. RESULTS: There were three
females and two males, ranging in age from 28 to 50 (mean 35.8) years. Most
patients (4/5) complained of a mass, discomfort or pain. MR images demonstrated a
heterogeneous, enhancing, soft tissue mass contiguous with the neurovascular
bundle. On histologic examination, most tumors were monophasic synovial sarcoma
(4/5). At the time of surgery, all tumors were noted to arise along or within a
peripheral nerve. All patients were alive with no evidence of disease with median
follow-up of 44 (range 32-237) months. For comparison, approximately 775 benign
peripheral nerve sheath tumors of the extremities were identified during the same
time period. CONCLUSIONS: Primary synovial sarcoma of the nerve can mimic
peripheral nerve sheath tumors clinically and on imaging and should be included
in the differential diagnosis for tumors arising from peripheral nerves.
PMID- 28689339
TI - Longitudinal Impact of a Park-Based Afterschool Healthy Weight Program on
Modifiable Cardiovascular Disease Risk Factors in Youth.
AB - Community-based programs hold significant potential to prevent cardiovascular
disease (CVD) risk in youth. We describe here the longitudinal change in several
modifiable CVD risk factors after participation in up to 3 years of Fit2PlayTM, a
park-based afterschool program. Children ages 6-15 years old (N = 2261, mean age
9.0 years, 50% Hispanic, 47% non-Hispanic black, 54% male) who participated in
Fit2PlayTM for either 1-3 school years between 2010 and 2016 had height, weight,
4-site skinfold thicknesses, systolic and diastolic blood pressure, the
progressive aerobic cardiovascular endurance run test, and health/wellness
knowledge and behavior scores collected at the beginning and end of the school
year(s). Effects of length of Fit2PlayTM participation on CVD outcomes were
assessed via 2-level repeated measures analysis adjusted for child
sociodemographics, park, area poverty, and year. Adjusted models showed
overweight/obese children who participated in up to 3 years of Fit2PlayTM had a
mean reduction of 8 mm in skinfold thicknesses; almost 0.5 SD's in BMI z-score; 5
DBP %ile points; 17% reduction in probability of developing hypertension; and a
mean increase of 6.4 PACER laps and 17% increase in health/wellness assessment
compared to baseline. A dose-response trend was found for years of Fit2PlayTM
participation and improved CVD risk profile in participating youth. In
conclusion, park-based afterschool programs that promote preventive CVD risk
strategies can be an equitable, low-cost, high value tool for addressing our
national epidemics of obesity, heart disease and diabetes and a rapidly changing
healthcare system in need of evidence-based prevention programs.
PMID- 28689340
TI - The Grocery Store Food Environment in Northern Greenland and Its Implications for
the Health of Reproductive Age Women.
AB - The population of Greenland is diminishing and environmental and social shifts
implicate food availability and the health of reproductive age women. There is
little knowledge of the grocery store food environment in Greenland. To address
this gap and provide baseline information the present study measured food
availability in five grocery stores in northern Greenland. As well, 15 interviews
were conducted with reproductive age women, three grocery store managers were
interviewed and one interview was conducted with a food distribution manager.
Results show few fresh fruits and vegetables are available in grocery stores and
in some stores no fresh foods are available. In Kullorsuaq, the primary location
for this study, the Nutrition Environment Measures Survey in Stores score in
spring 2016 was (3/30) and the Freedman Grocery Store Survey Score was (11/49).
Interview results highlight a need to increase communication within the food
system and to tailor food distribution policies to the Arctic context with longer
term planning protocols for food distribution. These findings can be used to
inform future food store environment research in Greenland and for informing
policies that improve healthful food availability in grocery stores in northern
Greenland.
PMID- 28689341
TI - Painful spasms in facial, masticatory, and motor ocular muscles reversed after
microvascular decompression of a neurovascular conflict at brainstem.
AB - The authors present a case of a 42-year-old female admitted for disabling complex
and atypical bilateral facial spasms associated with painful masticatory and
motor ocular dystonic movements, difficult to fit in the definition of any known
cranio-facial dyskinesias. MRI showed a left PICA loop invaginated into the
brainstem, considered responsible of an hyperactive disorder of the brainstem
nuclei neighboring the conflict. After microvascular decompression, the patient
made a full recovery with complete disappearance of the paroxystic phenomena.
Such a type of image should be searched for, in an intra-axial brainstem
location, in the absence of conflict in the cistern at root entry/exit zone
(REZ).
PMID- 28689342
TI - Superselective transvenous embolization with Onyx and n-BCA for vein of Galen
aneurysmal malformations with restricted transarterial access: safety, efficacy,
and technical aspects.
AB - PURPOSE AND METHODS: Superselective transvenous embolization (TVE) with liquid
embolic agents is a new concept in treatment of vein of Galen aneurysmal
malformations (VGAM). We performed ten sessions of TVE in VGAM patients with
restricted transarterial access. In this paper, we assessed clinical and
angiographic outcomes of the proposed treatment and discussed three different TVE
techniques with regard to morphology of the shunt and outflow tract. Safety and
avoidance-of-complication tips were also discussed. RESULTS: Patient age ranged
from 4 to 51 months. There were eight patients with choroidal VGAMs, seven of
them were successfully treated with Onyx, and in one case, transvenous
catheterization failed. In three cases, adjunctive coiling of draining vein was
performed. In three cases, normal deep cerebral veins were connected to the
outflow part of malformation; they were preserved during embolization in all
cases. Six-month follow-up angiography demonstrated angiographic cure in six
cases, and partial occlusion in one. There were two patients with mural VGAMs:
both were treated with n-BCA. Partial occlusion was achieved in both cases. There
was no procedure-related permanent morbidity or mortality. Oculomotor deficit due
to quadrigeminal ischemia occurred in one case, and resolved completely after 3
weeks. CONCLUSION: TVE with liquid embolic agents is a safe and effective salvage
method for VGAMs with restricted transarterial access, previously considered as
poor candidates for endovascular treatment.
PMID- 28689343
TI - A rare case report and literatures review on primary germinoma in cerebellar
hemisphere.
AB - OBJECT: Primary intracranial germinoma is a rare intracranial lesion which
accounts for approximately 0.5-2% of all intracranial tumors. Generally, primary
intracranial germinoma occurs in the midline structures of the central nervous
system of a pediatric patient. Only four cases of primary cerebellar germinomas
with poor prognosis have been previously reported. The object of this paper is to
introduce a case of germinoma originating from cerebellar hemisphere and to
discuss its clinical features. METHODS: This paper reported an 8-year-old boy who
was diagnosed to have cerebella inflammatory granuloma during hospitalization and
then discharged without any operation. However, the follow-up MRs revealed that
the lesion became larger. Therefore, the boy was hospitalized again and underwent
a gross total resection of lesion. According to pathological examination, the
final diagnosis was confirmed as germinoma. RESULTS: Chemo- and radiotherapy were
followed and so far, the patient showed good recovery without any recurrence and
metastasis. CONCLUSION: Primary cerebellar germinoma has been rarely described in
previous literatures. In this paper, a primary cerebellar germinoma was reported
and its clinical features and treatments were discussed. The tumor's significant
shrinkage by CT- scan was firstly reported and maybe this would provide a
valuable hint for the diagnosis and treatment on the intracranial germinomas in
children.
PMID- 28689344
TI - Neurological results of the modified treatment of epilepsy by stimulation of the
vagus nerve.
AB - INTRODUCTION: The vagus nerve stimulation (VNS) is used for treatment of drug
resistant epilepsy but laryngeal side effects are common. We tried to improve VNS
by modifying the implantation procedure. The aim was to reduce the rate of side
effects that have prevented using VNS to its full capacity. METHODS: We operated
on 74 pediatric patients for VNS device implantation using a modified surgical
protocol incorporating lower neck incision for electrode placement and 36
patients who were operated by standard technique were used for control group. We
retrospectively analyzed reduction in frequency of seizures, reduction in
severity of seizures (assessed by the shortened Ictal/post-ictal subscale of the
Liverpool Seizure Severity Scale that included falling to the ground, postictal
headache and sleepiness, incontinence, tongue biting, and injury during attack).
RESULTS: Using the new implantation technique, side effects related directly to
VNS therapy occurred in six cases (8.1%) showing statistically sound improvement
over the standard implantation technique (p ? 0.05). To achieve good results, the
maximum stimulation (3.5 mA) was used in 24 patients (32.4%), with no laryngeal
side effects detected. Twelve patients (16.2%) were seizure-free after the first
year of VNS treatment. 74.3% of patients experienced a 50% reduction in seizure
frequency and improved ictal or postictal activity. CONCLUSION: To minimize
laryngeal complications in implantation surgery for VNS devices, the surgical
technique may be modified, and lower neck incision could be used. A low rate of
laryngeal side effects allows using the VNS device to its full electrical
capacity.
PMID- 28689345
TI - Extensive brain infarction involving deep structures during an acetazolamide
challenged single-photon emission computed tomography scan in a patient with
moyamoya disease.
AB - BACKGROUND: Acetazolamide-challenged brain single-photon emission computed
tomography (SPECT) is used for the evaluation of cerebral perfusion in
cerebrovascular diseases including moyamoya disease (MMD). Not a few patients
experience adverse side effects during the acetazolamide-challenged brain SPECT,
but most of the symptoms are mild and transient. To our knowledge, this is the
first case report of severe brain infarction leading to death during the
examination of an acetazolamide-challenged brain SPECT in a patient with MMD.
CASE PRESENTATION: An 11-year-old girl who had been diagnosed of MMD demonstrated
sudden tonic movement during an acetazolamide-challenged brain SPECT as the
preoperative examination for the second surgery. She had not experienced any
adverse effect during the previous SPECT study and her first indirect bypass
surgery on both left side and bifrontal area was uneventful. After she had
seizures twice, she became unconscious and her pupils were dilated and fixed.
Acute infarction involving bilateral occipital lobes, thalami, brainstem, and
cerebellum was observed on brain magnetic resonance images which led to brain
death. CONCLUSION: We report a mortality case of patient with MMD after the
administration of acetazolamide during the examination of brain SPECT that was
accompanied by an extensive acute infarction involving the bilateral occipital
lobes and thalami, brainstem, and cerebellum. Physicians should be aware of this
rare but serious complication.
PMID- 28689346
TI - Electromagnetic navigation-guided neuroendoscopic removal of radiation-induced
intraforniceal cavernoma as a late complication of medulloblastoma treatment.
AB - INTRODUCTION: Medulloblastoma is the most frequent malignant brain tumour in
children. Radiation-induced cavernous haemangiomas (RICHs) are a known late
complication of radiation exposure, especially in young children. CASE REPORT: We
present a patient who underwent subtotal resection of posterior fossa
medulloblastoma with subsequent chemotherapy and radiotherapy at the age of 10
years. A new lesion in the region of the left foramen of Monro appeared 16 years
later. Based on the imaging results, metastasis or radiation-induced cavernoma
was considered. The lesion had the same appearance on imaging as a rarely
published intraventricular cavernoma of the foramen of Monro. Unlike the
cavernoma of the foramen of Monro, this lesion was subependymal and
intraforniceal. Using electromagnetic navigation and neuroendoscopy, the lesion
was completely removed. Histopathological examination revealed a cavernous
haemangioma. CONCLUSION: This is a unique case of intraforniceal paraforaminal
cavernoma that was successfully removed endoscopically using electromagnetic
neuronavigation and without neurological sequelae.
PMID- 28689347
TI - Youth's Causal Beliefs About Success: Socioeconomic Differences and Prediction of
Early Career Development.
AB - Youth's career attainment is associated with socioeconomic background, but may
also be related to their beliefs about causes of success. Relationships between
17-year-olds' socioeconomic status (SES) and causal beliefs about success, and
whether these beliefs predict career attainment after completing a vocational or
university degree were examined using data from the German Socio-Economic Panel
Study (n = 997, 48.5% female). Youth with higher SES parents and those who
attended higher levels of high schools were less likely to believe that success
in society is due to external causes, but SES was unrelated to the belief that
success is due to personal merit or ability. Youth who believe that success is
due to external causes attained lower income, occupational prestige, and job
autonomy, and slower increases in income over time. There were also significant
indirect effects of youth's parents' SES and their own high school levels on
career attainment through such external causal beliefs; merit beliefs, by
contrast, were largely unrelated to career attainment. These results suggest that
beliefs about external causes of success may uniquely contribute to the
transmission and maintenance of SES across generations and over time.
PMID- 28689348
TI - Parent-Adolescent Discrepancies in Reports of Parenting and Adolescent Outcomes
in Mexican Immigrant Families.
AB - Parents and adolescents often have discrepant views of parenting which pose
challenges for researchers regarding how to deal with information from multiple
informants. Although recent studies indicate that parent-adolescent discrepancies
in reports of parenting can be useful in predicting adolescent outcomes, their
findings are mixed regarding whether discrepancies relate to more positive or
more negative adolescent outcomes. This study examined the longitudinal
implications of parent-adolescent discrepancies in reports of parenting (warmth,
monitoring, and reasoning) on adolescent behavioral, psychological, academic, and
physical health outcomes among Mexican immigrant families in the United States.
Participants were 604 adolescents (54% female, M age.wave1 = 12.41 years) and
their parents. Taking a person-centered approach, this study identified distinct
patterns of parent-adolescent discrepancies in parenting and their different
associations with later adolescent outcomes. Adolescents' more negative
perceptions of parenting relative to parents were associated with more negative
adolescent outcomes, whereas adolescents' more positive perceptions relative to
parents related to more positive adolescent outcomes. There were also variations
in discrepancy patterns and their associations with adolescent outcomes between
mother-adolescent vs. father-adolescent dyads. Findings of the current study
highlight individual variations of discrepancies among parent-adolescent dyads
and the importance of considering both the magnitude and direction of
discrepancies regarding their associations with adolescent well-being.
PMID- 28689349
TI - Extreme longevity in a deep-sea vestimentiferan tubeworm and its implications for
the evolution of life history strategies.
AB - The deep sea is home to many species that have longer life spans than their
shallow-water counterparts. This trend is primarily related to the decline in
metabolic rates with temperature as depth increases. However, at bathyal depths,
the cold-seep vestimentiferan tubeworm species Lamellibrachia luymesi and
Seepiophila jonesi reach extremely old ages beyond what is predicted by the
simple scaling of life span with body size and temperature. Here, we use
individual-based models based on in situ growth rates to show that another
species of cold-seep tubeworm found in the Gulf of Mexico, Escarpia laminata,
also has an extraordinarily long life span, regularly achieving ages of 100-200
years with some individuals older than 300 years. The distribution of results
from individual simulations as well as whole population simulations involving
mortality and recruitment rates support these age estimates. The low 0.67%
mortality rate measurements from collected populations of E. laminata are similar
to mortality rates in L. luymesi and S. jonesi and play a role in evolution of
the long life span of cold-seep tubeworms. These results support longevity
theory, which states that in the absence of extrinsic mortality threats, natural
selection will select for individuals that senesce slower and reproduce
continually into their old age.
PMID- 28689350
TI - Repeated exposure to cat urine induces complex behavioral, hormonal, and c-fos
mRNA responses in Norway rats (Rattus norvegicus).
AB - Prey species show specific adaptations that allow recognition, avoidance, and
defense against predators. This study was undertaken to investigate the
processing of a chronic, life-threatening stimulus to Norway rats (Rattus
norvegicus). One hundred forty-four Norway rats were tested by repeated
presentation of cat urine for 1 h at different days in a defensive withdrawal
apparatus. Rats exposed to urine for short periods showed significantly larger
defensive behavioral and medial hypothalamic c-fos messenger RNA (mRNA) responses
than other groups. These defensive responses habituated shortly after the
presentation of cat urine. Serum levels of adrenocorticotropic hormone and
corticosterone increased significantly when animals were repeatedly exposed to
cat urine. However, the hormonal responses took longer to habituate than the
behavioral and molecular responses did. We conclude that the behavioral and c-fos
mRNA responses are "primed" for habituation to repeated exposures to cat urine,
while the hormonal responses show "resistance." The results support our
hypothesis that the strongest anti-predator responses at three levels would occur
during short-term exposure to cat urine and that these responses would
subsequently disappear on prolonged exposure. This study assists understanding
the way in which the different levels of defensive responses are integrated and
react during chronic stress.
PMID- 28689351
TI - Leveraging community-based participatory research capacity to recruit Pacific
Islanders into a genetics study.
AB - Pacific Islanders face many health disparities, including higher rates of
cardiovascular disease, cancer, obesity, and diabetes compared to other racial
and ethnic groups. Specifically, the Marshallese population suffers
disproportionately from type 2 diabetes, with rates 400% higher than the general
US population. As part of an ongoing community-based participatory research
(CBPR) partnership, 148 participants were recruited for a study examining genetic
variants to better understand diabetes. Participants provided a saliva specimen
in an Oragene(r) DNA self-collection kit. Each participant provided approximately
2 mL volume of saliva and was asked qualitative questions about their experience.
The study yielded a recruitment rate of 95.5%. Among the 148 persons who
participated, 143 (96.6%) agreed to be contacted for future studies; 142 (95.9%)
agreed to have their samples used for future IRB-approved studies; and 144
(97.3%) gave permission for the researchers to link information from this study
to other studies in which they had participated. Qualitative responses showed
that the majority of participants were willing to participate because of their
desire to contribute to the health of their community and to understand the
genetic influence related to diabetes. This study demonstrates willingness to
participate in genetic research among Marshallese living in Arkansas. Willingness
was likely enhanced because the feasibility study was part of a larger CBPR
effort. This study is important to community stakeholders who have voiced a
desire to collaboratively conduct genetic research related to diabetes, perinatal
outcomes, and cancer.
PMID- 28689352
TI - Synapse fits neuron: joint reduction by model inversion.
AB - In this paper, we introduce a novel simplification method for dealing with
physical systems that can be thought to consist of two subsystems connected in
series, such as a neuron and a synapse. The aim of our method is to help find a
simple, yet convincing model of the full cascade-connected system, assuming that
a satisfactory model of one of the subsystems, e.g., the neuron, is already
given. Our method allows us to validate a candidate model of the full cascade
against data at a finer scale. In our main example, we apply our method to part
of the squid's giant fiber system. We first postulate a simple, hypothetical
model of cell-to-cell signaling based on the squid's escape response. Then, given
a FitzHugh-type neuron model, we derive the verifiable model of the squid giant
synapse that this hypothesis implies. We show that the derived synapse model
accurately reproduces synaptic recordings, hence lending support to the
postulated, simple model of cell-to-cell signaling, which thus, in turn, can be
used as a basic building block for network models.
PMID- 28689353
TI - "Fabrication of arbitrarily shaped carbonate apatite foam based on the
interlocking process of dicalcium hydrogen phosphate dihydrate".
AB - Carbonate apatite (CO3Ap) foam with an interconnected porous structure is highly
attractive as a scaffold for bone replacement. In this study, arbitrarily shaped
CO3Ap foam was formed from alpha-tricalcium phosphate (alpha-TCP) foam granules
via a two-step process involving treatment with acidic calcium phosphate solution
followed by hydrothermal treatment with NaHCO3. The treatment with acidic calcium
phosphate solution, which is key to fabricating arbitrarily shaped CO3Ap foam,
enables dicalcium hydrogen phosphate dihydrate (DCPD) crystals to form on the
alpha-TCP foam granules. The generated DCPD crystals cause the alpha-TCP granules
to interlock with each other, inducing an alpha-TCP/DCPD foam. The interlocking
structure containing DCPD crystals can survive hydrothermal treatment with
NaHCO3. The arbitrarily shaped CO3Ap foam was fabricated from the alpha-TCP/DCPD
foam via hydrothermal treatment at 200 degrees C for 24 h in the presence of a
large amount of NaHCO3.
PMID- 28689354
TI - Functional and Molecular Characterization of a Novel Traumatic Peripheral Nerve
Muscle Injury Model.
AB - Traumatic injuries to human peripheral nerves are frequently associated with
damage to nerve surrounding tissues including muscles and blood vessels.
Currently, most rodent models of peripheral nerve injuries (e.g., facial or
sciatic nerve) employ surgical nerve transection with scissors or scalpels.
However, such an isolated surgical nerve injury only mildly damages neighboring
tissues and weakly activates an immune response. In order to provide a rodent
nerve injury model accounting for such nerve-associated tissue damage and immune
cell activation, we developed a drop tower-based facial nerve trauma model in
mice. We compare nerve regeneration in this novel peripheral nerve trauma model
with the established surgical nerve injury along several parameters. These
include gene expression, histological and functional facial motoneuron (FMN)
regeneration, facial nerve degeneration, immune cell activation and muscle
damage. Regeneration-associated genes (RAGs; e.g., Atf3) were strongly induced in
FMNs subjected to traumatic and surgical injury. Regeneration of FMNs and
functional recovery of whisker movement were faster in traumatic versus complete
surgical injury, thus cutting down experimentation time. Wallerian degeneration
of distal nerve stumps was readily observed in this novel trauma injury model.
Importantly, drop tower-inflicted facial nerve injury resulted in muscle damage,
activation of muscle satellite cell markers (PAX7) and pronounced infiltration of
immune cells to the injury site only in this model but not upon surgical nerve
transection. Thus, we provide a novel rodent PNS trauma model that can be easily
adopted to other PNS nerves such as the sciatic nerve. Since this nerve trauma
model replicates multiple tissue damage frequently encountered in clinical
routine, it will be well suited to identify molecular and cellular mechanisms of
PNS nerve repair in wild-type and genetically modified rodents.
PMID- 28689356
TI - Fluorodeoxyglucose-positron emission tomography/computed tomography performs
better than contrast-enhanced computed tomography for metastasis evaluation in
the initial staging of pancreatic adenocarcinoma.
AB - OBJECTIVE: To evaluate the additional role of FDG-PET/CT to the conventional
multiphasic CECT in the initial staging of pancreatic adenocarcinoma. METHODS: 54
patients diagnosed with pathologically proven pancreatic malignancy underwent FDG
PET/CECT. The sensitivity, specificity, PPV, NPV, and accuracy of PET/CT and CECT
for nodal and metastatic staging were calculated. The statistical difference was
calculated by McNemar's test. RESULTS: Of 54 patients, 15 had distal metastasis.
The sensitivity, specificity, PPV, NPV, and accuracy of PET/CT and CECT for nodal
staging were 33 vs 89%, 84 vs 100%, 67 vs 100%, 60 vs 90%, and 59 vs 95%,
respectively, p < 0.001. The sensitivity, specificity, PPV, NPV, and accuracy of
CECT for metastatic staging were 73, 87, 69, 89, and 83%, whereas the accuracy of
PET/CT was 100%, p = 0.01. By correctly characterizing unsuspected distant
lesions, PET/CT could change management in 19% of patients. CONCLUSION: FDG
PET/CT can contribute to change in the management in almost one of every five
patients of PA evaluated with the standard investigations during the initial
staging.
PMID- 28689355
TI - Vitamin D3 Reverses the Hippocampal Cytoskeleton Imbalance But Not Memory
Deficits Caused by Ovariectomy in Adult Wistar Rats.
AB - The objective of study was to investigate changes caused by ovariectomy (OVX) on
aversive and non-aversive memories, as well as on cytoskeleton phosphorylating
system and on vitamin D receptor (VDR) immunocontent in hippocampus. The
neuroprotective role of vitamin D was also investigated. Ninety-day-old female
Wistar rats were divided into four groups: SHAM, OVX, VITAMIN D and OVX + VITAMIN
D; 30 days after the OVX, vitamin D supplementation (500 IU/kg), by gavage, for
30 days was started. Results showed that OVX impaired short-term and long-term
recognition, and long-term aversive memories. OVX altered hippocampal
cytoskeleton phosphorylating system, evidenced by the hyperphosphorylation of
glial fibrillary acidic protein (GFAP), low molecular weight neurofilament
subunit (NFL), medium molecular weight neurofilament subunit (NFM) and high
molecular weight neurofilament subunit (NFH), and increased the immunocontent of
c-Jun N-terminal protein kinases (JNK), Ca2+/calmodulin-dependent protein kinase
II (PKCaMII) and of the sites phosphorylated lysine-serine-proline (KSP) repeats,
Ser55 and Ser57. Vitamin D reversed the effects caused by OVX on cytoskeleton in
hippocampus, but it was not able to reverse the effects on memory.
PMID- 28689357
TI - Cross calibration of 123I-meta-iodobenzylguanidine heart-to-mediastinum ratio
with D-SPECT planogram and Anger camera.
AB - BACKGROUND: Cardiac 123I-meta-iodobenzylguanidine (MIBG) uptake is quantified
using the heart-to-mediastinum ratio (HMR) with an Anger camera. The relationship
between HMR determined using D-SPECT with a cadmium-zinc-telluride detector and
an Anger camera is not fully understood. Therefore, the present study aimed to
define this relationship using images derived from a phantom and from patients.
METHODS: Cross-calibration phantom studies using an Anger camera with a low
energy high-resolution (LEHR) collimator and D-SPECT, and clinical 123I-MIBG
studies proceeded in 40 consecutive patients (80 studies). In the phantom study,
a conversion coefficient (CC) was defined based on phantom experiments and
applied to the Anger camera and the D-SPECT detector. The HMR was calculated
using anterior images with the Anger camera and anterior planograms with D-SPECT.
First, the HMR from D-SPECT was cross-calibrated to the Anger camera, and then,
the HMR from both cameras were converted to the medium-energy general-purpose
collimator condition (CC 0.88; ME88 condition). The relationship between HMR and
corrected and uncorrected methods was examined. A 123I-MIBG washout rate was
calculated using both methods with and without background subtraction. RESULTS:
Based on the phantom experiments, the CC of the Anger camera with an LEHR
collimator and of D-SPECT using an anterior planogram was 0.55 and 0.63,
respectively. The original HMR from the Anger camera and D-SPECT was 1.76 +/-
0.42 and 1.86 +/- 0.55, respectively (p < 0.0001). After D-SPECT HMR was
converted to the Anger camera condition, the corrected D-SPECT HMR became
comparable to the values under the Anger camera condition (1.75 +/- 0.48, p = n.
s.). When the HMR measured using the two cameras were converted under the ME88
condition, the average standardized HMR from the Anger camera and D-SPECT became
comparable (2.21 +/- 0.65 vs. 2.20 +/- 0.75, p = n. s.). After standardization to
the ME88 condition, a systematic difference in the linear regression lines
disappeared, and the HMR from both the Anger (StdHMRAnger) and D-SPECT
(StdHMRDSPECT) became comparable. Additional correction using a regression line
further improved the relationship between both HMR [StdHMRDSPECT = 0.09 + 0.98 *
StdHMRAnger (R 2 = 0.91)]. The washout rate closely correlated with and without
background correction between both methods (R 2 = 0.83 and 0.65, respectively).
CONCLUSION: The phantom-based conversion method is applicable to D-SPECT and
enables the common application of HMR irrespective of D-SPECT and the Anger
camera.
PMID- 28689358
TI - Comparison of Bayesian penalized likelihood reconstruction versus OS-EM for
characterization of small pulmonary nodules in oncologic PET/CT.
AB - OBJECTIVE: To determine whether the recently introduced Bayesian penalized
likelihood PET reconstruction (Q.Clear) increases the visual conspicuity and
SUVmax of small pulmonary nodules near the PET resolution limit, relative to
ordered subset expectation maximization (OS-EM). METHODS: In this institutional
review board-approved and HIPAA-compliant study, 29 FDG PET/CT scans performed on
a five-ring GE Discovery IQ were retrospectively selected for pulmonary nodules
described in the radiologist's report as "too small to characterize", or small
lung nodules in patients at high risk for lung cancer. Thirty-two pulmonary
nodules were assessed, with mean CT diameter of 8 mm (range 2-18). PET images
were reconstructed with OS-EM and Q.Clear with noise penalty strength beta values
of 150, 250, and 350. Lesion visual conspicuity was scored by three readers on a
3-point scale, and lesion SUVmax and background liver and blood pool SUVmean and
SUVstdev were recorded. Comparison was made by linear mixed model with modified
Bonferroni post hoc testing; significance cutoff was p < 0.05. RESULTS: Q.Clear
improved lesion visual conspicuity compared to OS-EM at beta = 150 (p < 0.01),
but not 250 or 350. Lesion SUVmax was increased compared to OS-EM at beta = 150
and 250 (p < 0.01), but not 350. CONCLUSION: In a cohort of small pulmonary
nodules with size near an 8 mm PET full-width half maximum, Q.Clear significantly
increased lesion visual conspicuity and SUVmax compared to our standard non- time
of-flight OS-EM reconstruction, but only with low noise penalization. Q.Clear
with beta = 150 may be advantageous when evaluation of small pulmonary nodules is
of primary concern.
PMID- 28689359
TI - Immunotoxic responses of chronic exposure to cypermethrin in common carp.
AB - In the current study, laboratory evaluations were made to assess the
immunomodulatory effect of cypermethrin on fingerlings of common carp (Cyprinus
carpio L.). Results showed that 96-h LC50 of cypermethrin in common carp was
estimated at 0.85 MUg/L. Fish were exposed for 21 days to cypermethrin at three
sub-lethal concentrations of 0.042, 0.085, and 0.17 MUg/L that represented 5, 10,
and 20%, respectively, of the 96-h LC50 of the pesticide for this fish species.
Blood samples were taken after 7, 14, and 21 days of exposure. Immunological
indices and resistance against bacterial infection were determined. Compared to
the control group, the fish exposed to cypermethrin showed a significant increase
in neutrophil ratio but exhibited a significant decrease in leukocyte number and
lymphocyte ratio in treatments exposed to 0.17 and/or 0.085 MUg/L after 21 days
of exposure (p < 0.05). Serum protein level was significantly decreased in group
exposed to 0.17 MUg/L on day 14 and also in groups exposed to 0.085 and 0.17
MUg/L on day 21 (p < 0.05). Immunoglobulin value was significantly reduced in
groups exposed to 0.085 and 0.17 MUg/L after 21 days of exposure (p < 0.05).
Serum lysozyme activity and phagocytic activity were significantly decreased
following exposure to 0.17 MUg/L determined on days 14 and 21, post-exposure (p <
0.05). Mortality rate following the challenge with Aeromonas hydrophila
significantly increased in fish exposed to 0.17 MUg/L of cypermethrin. Overall,
the present results indicate severe immunotoxicological effects of cypermethrin
in common carp. Therefore, the use of cypermethrin in the proximities of common
carp farms should be carefully considered.
PMID- 28689360
TI - Regulatory myeloid cells: an underexplored continent in B-cell lymphomas.
AB - In lymphomas arising from the germinal center, prognostic factors are linked to
the myeloid compartment. In particular, high circulating monocyte or myeloid
derived suppressor cell counts are associated with poor prognosis for patients
with high-grade B-cell lymphomas. Macrophages with an M2 phenotype are enriched
within lymphoma tumors. However, the M1/M2 nomenclature is now deprecated and the
clinical impact of this phenotype remains controversial. Across cancer types,
myeloid cells are primarily thought to function as immune suppressors during
tumor initiation and maintenance, but the biological mechanisms behind the
myeloid signatures are still poorly understood in germinal center B-cell
lymphomas. Herein, we describe the role and clinical relevance of myeloid cells
in B-cell lymphoma and propose innovative approaches to decipher this complex
cellular compartment. Indeed, characterization of this heterogeneous cell
ecosystem has been largely accomplished with "low-resolution" approaches like
morphological evaluation and immunohistochemistry, where cells are characterized
using a few proteins and qualitative metrics. High-resolution, quantitative
approaches, such as mass cytometry, are valuable to better understand myeloid
cell diversity, functions, and to identify potential targets for novel therapies.
PMID- 28689362
TI - Predictive factors on outcomes in metaplastic breast cancer.
AB - PURPOSE: Metaplastic breast cancer (MBC) is a rare, aggressive variant of breast
cancer, with limited data available regarding treatment and outcomes. This study
aims to review patients with MBC treated at our tertiary care institution with an
emphasis on the role of treatment modality and histologic classification.
METHODS: With IRB-approval, we queried our pathology database for patients with
MBC diagnosis. All cases were re-evaluated by dedicated breast pathologists and
confirmed as MBC breast cancer. Patient demographics, clinical/pathologic
histology, and treatment were analyzed with respect to outcomes including local
regional recurrence (LRR), distant metastasis (DM), and overall survival (OS).
Univariate and multivariate Cox proportional hazards models were performed to
evaluate the impact on outcomes. Kaplan-Meier methods estimated survival.
RESULTS: We evaluated 113 patients with MBC diagnosed between 2002 and 2013.
Median age was 61 years and median pathologic tumor size 2.5 cm; 76 (67%) were
ER/PR/Her2 negative, 83 (74%) grade 3. Median follow-up was 38 months. 47 (42%)
underwent breast conservation therapy (BCT), 66 (58%) had mastectomy, 61 (54%)
underwent adjuvant radiation (RT), and 85 (75%) had chemotherapy. At 2 and 5
years, the LRR/DM/OS rates were 12%/15%/90% and 21%/35%/69%, respectively. On Cox
regression analysis, only adjuvant RT correlated with reduced LRR [RR 3.1 (1.13
9.88), p = 0.027], while chemotherapy, type of surgery, and T-N stage did not.
Only T-stage (p = 0.008) correlated with DM, however chemotherapy, RT, surgery
type, and N-stage were not. Univariate analysis demonstrated histologic subtype
did not significantly correlate with local (p = 0.54) or distant (p = 0.83)
disease control. CONCLUSIONS: This study represents among the largest
institutional experiences in the outcomes of MBC. At this time, there does not
appear to be a clear histologic subset of MBC which has significantly different
clinical outcomes from the other subtypes. Although limited in its sample size,
this study shows RT remains important in local-regional control.
PMID- 28689361
TI - Reviewing the quality, health benefit and value for money of chemotherapy and
targeted therapy for metastatic breast cancer.
AB - PURPOSE: To provide an overview of model characteristics and outcomes of model
based economic evaluations concerning chemotherapy and targeted therapy (TT) for
metastatic breast cancer (MBC); to assess the quality of the studies; to analyse
the association between model characteristics and study quality and outcomes.
METHODS: PubMED and NHS EED were systematically searched. Inclusion criteria were
as follows: English or Dutch language, model-based economic evaluation,
chemotherapy or TT as intervention, population diagnosed with MBC, published
between 2000 and 2014, reporting life years (LY) or quality-adjusted life-year
(QALY) and an incremental cost-effectiveness ratio. General characteristics,
model characteristics and outcomes of the studies were extracted. Quality of the
studies was assessed through a checklist. RESULTS: 24 studies were included,
considering 50 comparisons (20 concerning chemotherapy and 30 TT). Seven
comparisons were represented in multiple studies. A health state-transition model
including the following health states: stable/progression-free disease,
progression and death was used in 18 studies. Studies fulfilled on average 14 out
of the 26 items of the quality checklist, mostly due to a lack of transparency in
reporting. Thirty-one per cent of the incremental net monetary benefit was
positive. TT led to higher iQALY gained, and industry-sponsored studies reported
more favourable cost-effectiveness outcomes. CONCLUSIONS: The development of a
disease-specific reference model would improve the transparency and quality of
model-based cost-effectiveness assessments for MBC treatments. Incremental health
benefits increased over time, but were outweighed by the increased treatment
costs. Consequently, increased health benefits led to lower value for money.
PMID- 28689363
TI - Risk of mortality of node-negative, ER/PR/HER2 breast cancer subtypes in T1, T2,
and T3 tumors.
AB - PURPOSE: The purpose of this study was to assess differences in breast cancer
specific mortality within tumors of the same size when breast cancer was defined
using the three tumor markers estrogen receptor (ER), progesterone receptor (PR),
and human epidermal growth factor receptor 2 (HER2). METHODS: We identified
104,499 cases of node-negative primary female invasive breast cancer from the
California Cancer Registry. Tumor size was categorized as T1a, T1b, T1c, T2, and
T3. Breast cancer was defined using ER, PR, and HER2. Kaplan-Meier Survival
analysis was conducted and Cox Regression was used to compute the adjusted risk
of mortality for the ER+/PR+/HER2+, ER-/PR-/HER2- (TNBC), and ER-/PR-/HER2+ (HER2
overexpressing) subtypes when compared with the ER+/PR+/HER2-. Separate models
were computed for each tumor size. RESULTS: Unadjusted survival analysis showed
that for all tumor sizes, the ER+/PR+ subtypes regardless of HER status have
better breast cancer-specific survival than ER-/PR- subtypes. Subtype was not an
important factor for risk of mortality for T1a tumors. The ER+/PR+/HER2+ subtype
was only a risk for mortality in T1b tumors that were unadjusted for treatment.
For all other tumor sizes, the ER+/PR+/HER2+ had the same mortality as the
ER+/PR+/HER2- subtype regardless of adjustment for treatment. The HER2
overexpressing subtype had a higher risk of mortality than the ER+/PR+/HER2-
subtype except for T1b tumors that were adjusted for treatment. For all tumor
sizes, the TNBC had higher hazard ratios than all other subtypes. CONCLUSIONS:
T1a tumors have the same risk of mortality regardless of ER/PR/HER2 subtype, and
ER and PR negativity plays a stronger role in survival than HER2 positivity for
tumors of all size.
PMID- 28689364
TI - Oncologists' influence on receipt of adjuvant chemotherapy: does it matter whom
you see for treatment of curable breast cancer?
AB - PURPOSE: We know little about whether it matters which oncologist a breast cancer
patient sees with regard to receipt of chemotherapy. We examined oncologists'
influence on use of recurrence score (RS) testing and chemotherapy in the
community. METHODS: We identified 7810 women with stages 0-II breast cancer
treated in 2013-15 through the SEER registries of Georgia and Los Angeles County.
Surveys were sent 2 months post-surgery, (70% response rate, n = 5080). Patients
identified their oncologists (n = 504) of whom 304 responded to surveys (60%). We
conducted multi-level analyses on patients with ER-positive HER2-negative
invasive disease (N = 2973) to examine oncologists' influence on variation in RS
testing and chemotherapy receipt, using patient and oncologist survey responses
merged to SEER data. RESULTS: Half of patients (52.8%) received RS testing and
27.7% chemotherapy. One-third (35.9%) of oncologists treated >50 new breast
cancer patients annually; mean years in practice was 15.8. Oncologists explained
17% of the variation in RS testing but little of the variation in chemotherapy
receipt (3%) controlling for clinical factors. Patients seeing an oncologist who
was one standard deviation above the mean use of RS testing had over two-times
higher odds of receiving RS (2.47, 95% CI 1.47-4.15), but a parallel estimate of
the association of oncologist with the odds of receiving chemotherapy was much
smaller (1.39, CI 1.03-1.88). CONCLUSIONS: Clinical algorithms have markedly
reduced variation in chemotherapy use across oncologists. Oncologists' large
influence on variation in RS use suggests that they variably seek tumor profiling
to inform treatment decisions.
PMID- 28689365
TI - Compromised inflammatory cytokine response to P. gingivalis LPS by fibroblasts
from inflamed human gingiva.
AB - OBJECTIVES: The aims of this study were to compare the in vitro cytokine response
of gingival fibroblasts (GF's) from healthy and inflamed human gingival tissues
and to assess whether GF's from inflamed gingivae are capable of mounting a
secondary inflammatory response after exposure to P. gingivalis LPS. MATERIALS
AND METHODS: GF's were obtained from healthy donors and periodontitis patients
and cultured in vitro. Cells were exposed to P. gingivalis LPS for 24h before
measurement of MCP-1, GRO, IL-6, IL-8 and VEGF using a bead-based multiplex
assay. Statistical comparisons were made between LPS-exposed GF's and
unstimulated cells as well as the two patient groups by two-way ANOVA. RESULTS:
GF's exposed to P. gingivalis LPS significantly increased their production of MCP
1, GRO, IL-6, IL-8 and VEGF compared to unstimulated cells. GF's isolated from
inflamed tissue from periodontitis patients demonstrated consistently less
cytokine production after exposure to P. gingivalis LPS, most notably for GRO and
IL-6. CONCLUSIONS: The current study demonstrates that GF's play an active role
in the inflammatory response in periodontal disease by producing a number of
chemokines and cytokines. Furthermore, inflamed GF's may be compromised in their
ability to mount an adequate secondary immune response in relation to
chemokine/cytokine production. CLINICAL RELEVANCE: The compromised inflammatory
cytokine response of inflamed human gingival fibroblasts to P. gingivalis LPS may
impact on their ability to recruit and activate inflammatory cells while
maintaining persistent inflammation, a key feature of periodontal disease.
PMID- 28689366
TI - Micro-CT and FE-SEM enamel analyses of calcium-based agent application after
bleaching.
AB - OBJECTIVES: The objective of the present study is to evaluate the effects of
casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) on bleached enamel.
MATERIALS AND METHODS: A bleaching agent (35% hydrogen peroxide) was applied, 4 *
8 min on premolar teeth (n = 8). A CPP-ACP paste was applied for 7 days. Prior
and post-treatment, microtomography images were obtained and 3D regions of
interest (ROIs) were selected, from outer enamel, extending to 110.2-MUm depth.
CT parameters of structure: thickness (St.Th), separation (St.Sp), and
fragmentation index (Fr.I.) were calculated for each (ROI). Data was submitted to
paired t tests at a 95% confidence level. The samples were evaluated at 3000 to
100,000 magnification. Quantitative analysis of enamel mineral content was also
determined by SEM EDX. RESULTS: There was a significant increase in structure
thickness and calcium content. The phosphorus content increased after bleaching.
There was also a decreased separation and fragmentation index on the outer enamel
to a depth of 56.2 MUm (p < 0.05). There were no changes at 110.2-MUm depth for
the bleaching CPP-ACP association. A covering layer and decreased spaces between
the hydroxyapatite crystals appeared around the enamel prisms, 7 days after the
CPP-ACP application. CONCLUSIONS: The application of a CPP-ACP provides a compact
structure on the enamel's outer surface, for 7 days, due to calcium deposition.
CT parameters seem to be a useful tool for mineralizing and remineralizing future
studies. CLINICAL RELEVANCE: CPP-ACP neutralizes any adverse effects on enamel
surface when applied during a week after bleaching and minimizes any side effects
of the bleaching treatment due to a more compact structure.
PMID- 28689367
TI - Rapidly Progressive Osteoarthritis: a Review of the Clinical and Radiologic
Presentation.
AB - PURPOSE OF REVIEW: The purpose of this paper is to review the distinct clinical
and radiographic features that may lead to prompt diagnosis of rapidly
progressive osteoarthritis (RPOA) and thus obviate unnecessary and costly
diagnostic workup. RECENT FINDINGS: RPOA is uncommon but is more frequently seen
in practice because of the aging population. RPOA is a destructive arthropathy
that occurs most commonly in elderly women but can also be seen in patients that
have sustained trauma. The dramatic radiologic manifestations of RPOA can lead to
diagnostic confusion with other arthropathies, infection, and osteonecrosis. RPOA
was originally described in the hip but may also involve the shoulder. The
etiology of RPOA is not well understood, but subchondral fracture probably plays
a role in the development of dramatic destruction of the joint that is seen in
affected patients. Early diagnosis may reduce the complexity of surgical
management. RPOA is an uncommon condition that occurs most frequently in elderly
woman or in patients who have sustained trauma. Prompt recognition of the
clinical and radiologic features of this arthropathy can reduce unnecessary
diagnostic workup and complexity of surgical intervention.
PMID- 28689368
TI - Maximize surgical resection beyond contrast-enhancing boundaries in newly
diagnosed glioblastoma multiforme: is it useful and safe? A single institution
retrospective experience.
AB - The extent of surgical resection (EOR) has been recorded as conditioning outcome
in glioblastoma multiforme (GBM) patients but no significant improvements were
recorded in survival. The study aimed to evaluate the impact of EOR on survival,
investigating the role of fluid-attenuated inversion recovery (FLAIR)
abnormalities removal. 282 newly diagnosed GBM patients were treated with surgery
followed by concurrent and adjuvant chemo-radiotherapy. The EOR was defined as:
SUPr, in case of resection amounting to 100% of enhanced and FLAIR areas; gross
total (GTR) in case of resection between 90 and 100% of enhanced areas with
variable amount of FLAIR abnormalities; sub-total (STR), between 10 and 89%;
biopsy (B) <10%. FLAIR-RTV was dichotomized in percentage values to identify the
best separation threshold for progression free survival (PFS) and overall
survival (OS). SUPr was obtained in 21 patients (7.4%), GTR in 60 (21.3%), STR in
143 (50.7%) and biopsy only in 58 (20.6%). The median, 1, 2-year PFS were 10.4 +/
0.4 months, 39.0 +/- 3.0, and 17.0 +/- 2.0%; the median, 1, 2-year OS were 14.5
+/- 0.5 months, 63.3 +/- 3.0, and 23.1 +/- 3.1%. EOR was significantly
influencing survival (p < 0.001). The median, 1, 2-year OS were 28.6 +/- 5.2
months, 90.0 +/- 6.0, 71.0 +/- 10.0% for patients underwent SUPr vs. 16.2 +/- 1.2
months, 81.0 +/- 5.0, 24.0 +/- 6.0% for GTR. The FLAIR removal threshold
conditioning survival was 45%. Minor complications were recorded in 14 (5%)
patients and major in 8 (2.8%). surgical resection beyond contrast-enhancing
boundaries could represent a promising strategy to improve outcome in GBM
patients. The identification of a FLAIR-RTV threshold can be useful in clinical
practice and it was recorded as factor influencing survival.
PMID- 28689369
TI - STAT6 Reliably Distinguishes Solitary Fibrous Tumors from Myofibromas.
AB - Solitary fibrous tumors (SFT) and myofibromas (MF) historically have belonged to
the same morphologic spectrum and have been lumped together under the nonspecific
umbrella term, "hemangiopericytoma" along with other pericytic/myoid tumors.
While current evidence shows clear distinction between the two entities, they
frequently remain in the same histopathologic differential diagnosis. This
diagnostic dilemma especially is common for smaller incisional biopsies from the
oral cavity. STAT6 immunohistochemistry (IHC) recently was established as a
reliable method to detect solitary fibrous tumor; however, the literature is
sparse regarding STAT6 reactivity in MFs. The authors report ten new cases of
oral solitary fibrous tumor, discuss histopathologic similarities and differences
between the two tumors, and list respective STAT6 IHC expressivity. After IRB
approval, 10 cases diagnosed as SFT and 24 cases of MF were collected from the
University of Florida Oral and Maxillofacial Pathology Biopsy Service between the
years 1994 and 2016. The original hematoxylin and eosin slides and related IHC
were reviewed. IHC with STAT6 antibody was performed on all 34 samples, and the
findings were analyzed. All cases were from the oral cavity or perioral regions.
10/10 SFTs expressed STAT6 nuclear reactivity, while no cases of MF showed
nuclear expression of STAT6. STAT6 is a dependable marker to differentiate SFTs
from MFs.
PMID- 28689370
TI - Intra-Target Microdosing - A Novel Drug Development Approach: Proof of Concept,
Safety, and Feasibility Study in Humans.
AB - Intra-Target Microdosing (ITM) is a novel drug development approach aimed at
increasing the efficiency of first-in-human (FIH) testing of new molecular
entities (NMEs). ITM combines intra-target drug delivery and "microdosing," the
subpharmacological systemic exposure. We hypothesized that when the target tissue
is small (about 1/100th of total body mass), ITM can lead to target therapeutic
level exposure with minimal (microdose) systemic exposure. Each of five healthy
male volunteers received insulin microdose into the radial artery or full
therapeutic dose intravenously in separate visits. Insulin and glucose levels
were similar between systemic administration and ITM administration in the
ipsilateral hand, and glucose levels demonstrated a reduction in the ipsilateral
hand but not in the contralateral hand. Positron emission tomography (PET)
imaging of 18 F-fluorodeoxyglucose (FDG) uptake demonstrated differences between
the ipsilateral and contralateral arms. The procedures were safe and well
tolerated. Results are consistent with ITM proof-of-concept (POC) and demonstrate
the ethical, regulatory, and logistical feasibility of the approach.
PMID- 28689371
TI - Erratum: Breast Cancer-Major changes in the American Joint Committee on Cancer
eighth edition cancer staging manual.
PMID- 28689372
TI - Deficits of ankle muscle strength not found in children, adolescents and young
adults with haemophilic ankle arthropathy.
AB - OBJECTIVES: Adequate management of haemophilia patients requires early detection
of joint impairment in relatively asymptomatic patients. This study sought to
quantify the impact of the ankle's structural impairment on muscle strength in
children, adolescent and young adults with haemophilia (CAAwH). METHODS: Twenty
three CAAwH underwent bilateral magnetic resonance imaging (MRI) assessing the
anatomical status of tibiotalar joint (TTJ) and subtalar joint (STJ) using the
International Prophylaxis Study Group MRI scale. An isokinetic dynamometer
enabled a detailed evaluation of muscle strength at slow and fast speed. In
parallel, 10 typically developing healthy boys (TDB) participated in a 1-week
interval test-retest assessment to assess the test's reliability. RESULTS: Forty
six MRI ankle scores were obtained, with 11 patients unilaterally affected and
one bilaterally. Of the 13 affected feet, nine showed abnormalities at TTJ, three
at the posterior STJ and the remaining one at both joints. Muscle strength was
not reduced in CAAwH exhibiting TTJ and/or STJ arthropathy, as compared to
healthy TDB, nor was there any difference between the CAAwH's affected or
unaffected sides. CONCLUSION: Contrarily to adult patients, CAAwH with repeated
ankle bleeding may be less impaired than current structural evaluations imply,
with possibly a latency between the occurrence of structural and functional
damage.
PMID- 28689373
TI - Caseous calcification of the left aortic valve cusp.
PMID- 28689374
TI - Identification of OAT1/OAT3 as Contributors to Cisplatin Toxicity.
AB - Cisplatin is among the most widely used anticancer drugs and known to cause a
dose-limiting nephrotoxicity, which is partially dependent on the renal uptake
carrier OCT2. We here report a previously unrecognized, OCT2-independent pathway
of cisplatin-induced renal injury that is mediated by the organic anion
transporters OAT1 and OAT3. Using transporter-deficient mouse models, we found
that this mechanism regulates renal uptake of a mercapturic acid metabolite of
cisplatin that acts as a precursor of a potent nephrotoxin. The function of these
two transport systems can be simultaneously inhibited by the tyrosine kinase
inhibitor nilotinib through noncompetitive mechanisms, without compromising the
anticancer properties of cisplatin. Collectively, our findings reveal a novel
pathway that explains the fundamental basis of cisplatin-induced nephrotoxicity,
with potential implications for its therapeutic management.
PMID- 28689376
TI - Comparative study of the prevalence of clotting factor deficiency in carriers of
haemophilia A and haemophilia B.
PMID- 28689377
TI - [Exosomal microRNAs as a part of the cell-cell communication in cancer].
AB - Exosomes are small membrane vesicles released by several types of cells into the
extracellular matrix. They contain both, proteins and nucleic acids, including
DNA fragments, mRNAs, microRNAs, and other non-coding RNAs, that can be
transported to the recipient cells. They are one of the key elements of
intercellular communication that occurs in the tumor microenvironment. Recently
studies have shown that exosomal microRNAs are involved in the regulation of cell
migration and invasiveness, angiogenesis, metastasis, and the modulation of
immune response against cancer. Moreover, exosomal microRNAs could be also
potential cancer biomarkers. This review summarizes the current knowledge about
biogenesis of exosomal microRNAs and their role in the tumorigenesis.
PMID- 28689375
TI - Psychotropic polypharmacy in Australia, 2006 to 2015: a descriptive cohort study.
AB - AIMS: To describe psychotropic polypharmacy in Australia between 2006 and 2015.
METHODS: We used pharmaceutical claims from a national 10% sample of people with
complete dispensing histories to estimate the annual prevalence of the combined
use (overlap of >60 days exposure) of >=2 psychotropics overall and within the
same class or subclass (class and subclass polypharmacy). We also estimated the
proportion of polypharmacy episodes involving one, two, three and four or more
unique prescribers. RESULTS: The prevalence of class polypharmacy between 2006
and 2015 in people dispensed specific psychotropic classes was 5.9-7.3% for
antipsychotics, 2.1-3.7% for antidepressants and 4.3-2.9% for benzodiazepines.
The prevalence of antipsychotic polypharmacy was higher than expected given the
prevalence of antipsychotic exposure and combinations of sedating agents were
notably common. Overall, 26.7% of polypharmacy episodes involved multiple
prescribers but having multiple prescribers occurred more frequently for class
and subclass polypharmacy and people with four or more concomitant psychotropics.
DISCUSSION: Psychotropic polypharmacy is common, despite limited evidence of
risks and benefits. Increases in polypharmacy with multiple prescribers may be
due to poor communication with patients and between health care professionals.
PMID- 28689378
TI - The roles of annexins in vascular endothelium dysfunction accompanying diabetes
mellitus type 2.
AB - Impairment in cellular transport, distribution and storage of cholesterol
accompanies insulin resistance and diabetes mellitus type 2 as well as other
diseases such as obesity, atherosclerosis, and non-alcoholic fatty liver disease.
Diabetes mellitus type 2 is a metabolic disorder that is characterized by
hyperglycemia in the context of insulin resistance and relative lack of insulin.
Type 2 diabetes makes up about 90% of cases of diabetes. Several therapeutic
strategies are today being considered to target diabetes mellitus type 2, and the
accompanying endothelial dysfunction, but none as yet has proved satisfactory.
Accumulating data suggest that annexins, as cholesterol binding proteins that
participate in intracellular transport and storage of cholesterol and in the
organization of plasma membrane, may participate in development and sustenance of
diabetes mellitus type 2 and may serve as predictive markers of this disease.
PMID- 28689379
TI - [Influence of conjugated linoleic acids on metabolic processes in cells and
tissues].
AB - Conjugated linoleic acids (CLA) are constitutional and geometric isomers of this
acid. The most commonly consumed geometric isomers are cis-9,trans-11 (c9, t11)
CLA and trans-10, cis-12 (t10,c12) CLA. These isomers together with trans-9,trans
11 CLA and trans-10,trans-12 CLA constitute about 90% of all CLA in natural
products. Different structure of the isomers affects their functions in the body.
Differences in the effects on organs and tissues are sometimes small and
sometimes opposed, sometimes the isomers work synergistically. Diverse influence
has been shown mainly in neoplastic processes and lipid metabolism. For example,
differences in inhibition of proliferation of prostate cancer cells are explained
by different pathways: t10,c12 CLA acts on apoptosis and cell cycle control
genes, while c9,t11 CLA regulates genes involved in metabolism of arachidonic
acid with subsequent impairment of eicosanoids synthesis. Other studies have
shown that t10,c12 CLA, but not c9,t11 CLA, can induce fat reduction in adipose
tissue and apoptosis of adipocytes in mice.
PMID- 28689380
TI - [Conformations of multi-domain and partially disordered proteins - simulations
and experiments].
AB - Structural biology unravels three-dimensional structures of macromolecules such
as proteins, DNA, RNA, and their complexes in the attempt to explain the basic
mechanisms of their functions. Among the proteins that are most difficult to
characterize structurally are those which have several large domains connected by
long, unstructured polypeptide segments. Such proteins perform diverse functions
in living organisms and, at the same time, they are very difficult to
characterize using conventional methods of structural biology. This gap in the
market has recently led to the development of hybrid methods that use state-of
the-art computational tools to combine complementary data from various
experiments. This review article is focused on the implementation and usage of
such hybrid methods. It includes a detailed description of how representative
structures of multi-domain proteins are obtained using the so-called EROS
(Ensemble Refinement of SAXS) hybrid method.
PMID- 28689381
TI - [Methods of analysis of protein phosphorylation].
AB - Phosphorylation and dephosphorylation play a fundamental role in most signaling
pathways, as these processes can directly regulate various aspects of protein
function. It is estimated that there are about 100,000 potential phosphorylation
sites in proteins encoded by the human genome and about 30-50% of all proteins in
the cell can be phosphorylated, which is directly related to the functions they
perform. To determine whether a given protein is phosphorylated, any changes in
its mobility caused by this modification are examined during PAGE
electrophoresis. Concurrently, tandem mass spectrometry (MS/MS) allows to
identify specific phosphorylation sites. The next step involves the prediction
(using in silico analysis) which kinases can phosphorylate a specific site in the
given protein. Then, in order to verify the information obtained from databases,
in vitro and/or in vivo experiments are carried out.
PMID- 28689382
TI - [Potential application for stem cells in regenerative medicine and
transplantology].
AB - There are some cells in human body which have an ability to self-renewal and
differentiation into particular type of cell. They are classified according to
the source of gain and ability to differentiate. Several studies carry on
directed stem cells programming toward formation of particular type of cells and
also reprogramming somatic stem cells for induced pluripotent stem cells. In the
future it could bring hope in elaboration of new ways of disease curing that will
give a chance for getting healthy (especially cancers). Stem cells display
application in regenerative medicine. They facilitate in repair of damaged or
dysfunctional tissues using cells derived from patients. In many cancer types the
presence of cancer stem cells was observed. Their ability to self-renewal and
unlimited proliferation might be the reason of metastasis and relapse of cancer.
The knowledge on complexed signaling pathways and mechanisms of their regulation
may be crucial and should lead to elaboration of effective anticancer therapies.
PMID- 28689383
TI - [Apnea of prematurity - characteristic and treatment].
AB - Apnea of prematurity (AOP) can affect even 85-100% of premature newborns and is
related to lack of full maturity of organs. AOP is manifesting by 15-20 seconds
cessations of breathing accompanied by bradycardia and oxygen desaturation, what
can lead to hypoxia or death. Therefore it is very important to implement the
effective and safe treatment immediately after birth. Widely used caffeine
citrate, which stimulates the respiratory system, improving the working of the
respiratory muscles. However the metabolism of caffeine citrate is difficult in
preterm infants due to the immaturity of the hepatic enzyme system, what can lead
to the occurrence of side effects and toxicity. To avoid the toxic effects of
caffeine, and at the same time the lack of efficacy associated with
administration of too low doses, this therapy should be monitored by measuring
the concentration of caffeine in the plasma of treated infants. This would
provide the maintenance of therapeutic levels of caffeine and optimization of the
treatment.
PMID- 28689384
TI - Cross-talk between Src kinases and Rho small GTPases regulates biomineralization
and simplify imaging of the mineralization process.
AB - The process of physiological mineralization that occurs during bone ossification
is a tightly regulated cascade of molecular events leading to formation of bony
skeleton. Its deregulation associated with aging leads to pathological
mineralization not only in osseous but also in soft tissues. Recent discoveries
in the field of bone biology indicate the participation of the Src family of
tyrosine kinases as well as the Rho family of small GTPases in mineral formation.
Cross-talk between these two signaling pathways is activated during an early step
of the mineralization process, and leads to reorganization of the cytoskeleton of
mineralization-competent cells and to matrix vesicles release. The understanding
of mechanisms of the cross-talk between Src kinases and Rho small GTPases that
regulate the mineralization process is crucial for the development of novel
simply imaging techniques and therapeutic strategies in relation to pathological
mineralization.
PMID- 28689385
TI - Expression Optimization of Anti-CD22 scFv-Apoptin Fusion Protein Using
Experimental Design Methodology
AB - Background: Design of experiments is a rapid and cost-effective approach for
optimization of recombinant protein production process. In our previous study, we
generated a potent dual-acting fusion protein, anti-CD22 scFv-apoptin, to target
B-cell malignant cell lines. In the present investigation, we report the effect
of different variables on the expression levels of this fusion protein. Methods:
Four variables (cell optical density at induction, IPTG concentration, induction
temperature, and induction time) were tested using experimental design. Results:
Our findings demonstrated that among the examined variables, only the induction
time had a significant positive effect on the protein expression yield.
Conclusion: Experimental design was successfully applied in this study. The
optimized condition obtained in the current study can be applied in future
commercial production of this novel fusion protein.
PMID- 28689386
TI - Surgical Informed Consent Process in Neurosurgery.
AB - The doctrine of informed consent, as opposed to medical paternalism, is intended
to facilitate patient autonomy by allowing patient participation in the medical
decision-making process. However, regrettably, the surgical informed consent
(SIC) process is invariably underestimated and reduced to a documentary procedure
to protect physicians from legal liability. Moreover, residents are rarely
trained in the clinical and communicative skills required for the SIC process.
Accordingly, to increase professional awareness of the SIC process, a brief
history and introduction to the current elements of SIC, the obstacles to patient
autonomy and SIC, benefits and drawbacks of SIC, planning of an optimal SIC
process, and its application to cases of an unruptured intracranial aneurysm are
all presented. Optimal informed consent process can provide patients with a good
comprehension of their disease and treatment, augmented autonomy, a strong
therapeutic alliance with their doctors, and psychological defenses for coping
with stressful surgical circumstances.
PMID- 28689387
TI - Ginkgolide B Modulates BDNF Expression in Acute Ischemic Stroke.
AB - OBJECTIVE: To investigate the neuroprotective effects of Ginkgolide B (GB)
against ischemic stroke-induced injury in vivo and in vitro, and further explore
the possible mechanisms concerned. METHODS: Transient middle cerebral artery
occlusion (tMCAO) mice and oxygen-glucose deprivation/reoxygenation (OGD/R)
treated N2a cells were used to explore the neuroprotective effects of GB. The
expression of brain-derived neurotrophic factor (BDNF) was detected via Western
blot and qRT-PCR. RESULTS: GB treatment (4 mg/kg, i. p., bid) significantly
reduced neurological deficits, water content, and cerebral infarct volume in
tMCAO mice. GB also significantly increased Bcl-2/Bax ratio, reduced the
expression of caspase-3, and protected against OGD/R-induced neuronal apoptosis.
Meanwhile, GB caused the up-regulation of BDNF protein in vivo and in vitro.
CONCLUSION: Our data suggest that GB might protect the brain against ischemic
insult partly via modulating BDNF expression.
PMID- 28689388
TI - Osteoblast and Bacterial Culture from Cryopreserved Skull Flap after Craniectomy:
Laboratory Study.
AB - OBJECTIVE: Cranioplasty using a cryopreserved skull flap is a wide spread
practice. The most well-known complications of cranioplasty are postoperative
surgical infections and bone flap resorption. In order to find biological
evidence of cryopreserved cranioplasty, we investigated microorganism
contamination of cryopreserved skulls and cultured osteoblasts from cryopreserved
skulls. METHODS: Cryopreserved skull flaps of expired patients stored in a bone
bank were used. Cryopreserved skulls were packaged in a plastic bag and wrapped
with cotton cloth twice. After being crushed by a hammer, cancellous bone between
the inner and outer table was obtained. The cancellous bone chips were thawed in
a water bath of 30 degrees C rapidly. After this, osteoblast culture and general
microorganism culture were executed. Osteoblast cultures were done for 3 weeks.
Microorganism cultures were done for 72 hours. RESULTS: A total of 47
cryopreserved skull flaps obtained from craniectomy was enrolled. Of the sample,
11 people were women, and the average age of patients was 55.8 years. Twenty four
people had traumatic brain injuries, and 23 people had vascular diseases. Among
the patients with traumatic brain injuries, two had fracture compound comminuted
depressed. The duration of cryopreservation was, on average, 83.2 months (9 to
161 months). No cultured osteoblast was observed. No microorganisms were
cultured. CONCLUSION: In this study, neither microorganisms nor osteoblasts were
cultured. The biological validity of cryopreserved skulls cranioplasty was
considered low. However, the usage of cryopreserved skulls for cranioplasty is
worthy of further investigation in the aspect of cost-effectiveness and risk
benefit of post-cranioplasty infection.
PMID- 28689389
TI - Is There Additive Therapeutic Effect When GCSF Combined with Adipose-Derived Stem
Cell in a Rat Model of Acute Spinal Cord Injury?
AB - OBJECTIVE: Functional and neural tissue recovery has been reported in many animal
studies conducted with stem cells. However, the combined effect of cytokines and
stem cells has not yet been adequately researched. Here, we analyzed the additive
effects of granulocyte colony-stimulating factor (GCSF) on adipose-derived stem
cells (ADSCs) infusion in the treatment of acute spinal cord injury (SCI) in
rats. METHODS: Four days after intrathecal infusion tubes implantation in Sprague
Dawley rats, SCI was induced with an infinite horizon impactor. In the Sham group
(n=5), phosphate-buffered saline was injected 3, 7, and 14 days after SCI. GCSF,
ADSCs, and ADSCs with GCSF were injected at the same time in the GCSF (n=8), ADSC
(n=8), and ADSC+GCSF groups (n=7), respectively. RESULTS: The ADSC and ADSC+GCSF
groups, but not the GCSF group, showed significantly higher Basso-Beattie
Bresnahan scores than the Sham group during 8 weeks (p<0.01), but no significant
difference between the ADSC and ADSC+GCSF groups. In the ladder rung test, all
four groups were significantly different from each other, with the ADSC+GCSF
group showing the best improvement (p<0.01). On immunofluorescent staining
(GAP43, MAP2), western blotting (GAP43), and reverse transcription polymerase
chain reaction (GAP43, nerve growth factor), the ADSC and ADSC+GCSF groups showed
higher levels than the Sham and GCSF groups. CONCLUSION: Our analyses suggest
that the combination of GCSF and ADSCs infusions in acute SCI in the rat does not
have a significant additive effect. Hence, when combination agents for SCI stem
cell therapy are considered, molecules other than GCSF, or modifications to the
methodology, should be investigated.
PMID- 28689390
TI - Usefulness of End-to-Side Bridging Anastomosis of Sural Nerve to Tibial Nerve: An
Experimental Research.
AB - OBJECTIVE: Repair of sensorial nerve defect is an important issue on peripheric
nerve surgery. The aim of the present study was to determine the effects of
sensory-motor nerve bridging on the denervated dermatomal area, in rats with
sensory nerve defects, using a neural cell adhesion molecule (NCAM). METHODS: We
compared the efficacy of end-to-side (ETS) coaptation of the tibial nerve for
sural nerve defect repair, in 32 Sprague-Dawley rats. Rats were assigned to 1 of
4 groups: group A was the sham operated group, group B rats had sural nerves
sectioned and buried in neighboring muscles, group C experienced nerve sectioning
and end-to-end (ETE) anastomosis, and group D had sural nerves sectioned and ETS
anastomosis was performed using atibial nerve bridge. Neurological evaluation
included the skin pinch test and histological evaluation was performed by
assessing NCAM expression in nerve terminals. RESULTS: Rats in the denervated
group yielded negative results for the skin pinch tests, while animals in the
surgical intervention groups (group C and D) demonstrated positive results. As
predicted, there were no positively stained skin specimens in the denervated
group (group B); however, the surgery groups demonstrated significant staining.
NCAM expression was also significantly higher in the surgery groups. However, the
mean NCAM values were not significantly different between group C and group D.
CONCLUSION: Previous research indicates that ETE nerve repair is the gold
standard for peripheral nerve defect repair. However, ETS repair is an effective
alternative method in cases of sensorial nerve defect when ETE repair is not
possible.
PMID- 28689391
TI - The Incidence and Characteristics of Patients with Small Ruptured Aneurysms (<5
mm) in Subarachnoid Hemorrhage.
AB - OBJECTIVE: Small unruptured aneurysms (<5 mm) are known for their very low risk
of rupture, and are recommended to be treated conservatively. However, we
encounter many patients with small ruptured aneurysms in the clinical practice.
We aimed to investigate the incidence and characteristics of patients with small
ruptured aneurysms. METHODS: We reviewed all patients admitted to our hospital
with subarachnoid hemorrhage from January 2005 to December 2015. The patients
were divided into two groups: those with aneurysms <5 mm (group S) and those with
aneurysms >=5 mm (group L). The patient's age and sex, size and location of
aneurysms, and risk factors such as hypertension, diabetes, alcohol use, and
smoking were compared between the two groups. RESULTS: Eight-hundred eleven
patients were diagnosed with ruptured aneurysms, and 337 (41.6%) were included in
group S. The mean size of all aneurysms was 6.10+/-2.99 mm (range, 0.7-37.7);
aneurysms with a diameter of 4-5 mm accounted for the largest subgroup of all
aneurysms. Female sex was significantly associated with the incidence of small
ruptured aneurysms (odds ratio [OR] 1.50, 95% confidence intervals [CI] 1.02
2.19, p=0.037). Despite female predominance in the incidence of small ruptured
aneurysms, the proportion of small ruptured aneurysms in young (<50 years) men
was high. In men, there were no significant differences regarding the location of
the aneurysms between group S and group L (p=0.267), with the most frequent
location being the anterior communicating artery (ACoA) in both group S (50.9%)
and group L (51.4%). However, in women, there were significant differences
regarding the location of the aneurysms between group S and group L (p=0.023),
with the most frequent locations being the ACoA (33.0%) in group S, and the
posterior communicating artery (30.6%) in group L. In women, two locations were
significantly associated with small (<5 mm) ruptured aneurysms: the ACoA (OR
2.14, 95% CI 1.01-4.54, p=0.047) and anterior cerebral artery (OR 3.54, 95% CI
1.19-10.54, p=0.023). Multiplicity and smoking were significantly associated with
large (>=5 mm) ruptured aneurysms in women. The use of alcohol was related to
small ruptured aneurysms in men over 50 years of age (OR 2.23, 95% CI 1.03-4.84,
p=0.042). CONCLUSION: In this study, small (<5 mm) ruptured aneurysms exhibited
different incidences by age, sex, location, and risk factors such as
multiplicity, smoking, and alcohol use.
PMID- 28689392
TI - Preservation of Motion at the Surgical Level after Minimally Invasive Posterior
Cervical Foraminotomy.
AB - OBJECTIVE: Although minimally invasive posterior cervical foraminotomy (MI-PCF)
is an established approach for motion preservation, the outcomes are variable
among patients. The objective of this study was to identify significant factors
that influence motion preservation after MI-PCF. METHODS: Forty-eight patients
who had undergone MI-PCF between 2004 and 2012 on a total of 70 levels were
studied. Cervical parameters measured using plain radiography included C2-7 plumb
line, C2-7 Cobb angle, T1 slope, thoracic outlet angle, neck tilt, and disc
height before and 24 months after surgery. The ratios of the remaining facet
joints after MI-PCF were calculated postoperatively using computed tomography.
Changes in the distance between interspinous processes (DISP) and the segmental
angle (SA) before and after surgery were also measured. We determined successful
motion preservation with changes in DISP of <=3 mm and in SA of <=2 degrees .
RESULTS: The differences in preoperative and postoperative DISP and SA after MI
PCF were 0.03+/-3.95 mm and 0.34+/-4.46 degrees , respectively, fulfilling the
criteria for successful motion preservation. However, the appropriate level of
motion preservation is achieved in cases in which changes in preoperative and
postoperative DISP and SA motions are 55.7 and 57.1%, respectively. Based on
preoperative and postoperative DISP, patients were divided into three groups, and
the characteristics of each group were compared. Among these, the only
statistically significant factor in motion preservation was preoperative disc
height (Pearson's correlation coefficient=0.658, p<0.001). The optimal disc
height for motion preservation in regard to DISP ranges from 4.18 to 7.08 mm.
CONCLUSION: MI-PCF is a widely accepted approach for motion preservation,
although desirable radiographic outcomes were only achieved in approximately half
of the patients who had undergone the procedure. Since disc height appears to be
a significant factor in motion preservation, surgeons should consider disc height
before performing MI-PCF.
PMID- 28689393
TI - Inter- and Intra-Observer Variability of the Volume of Cervical Ossification of
the Posterior Longitudinal Ligament Using Medical Image Processing Software.
AB - OBJECTIVE: Computed tomography (CT)-based method of three dimensional (3D)
analysis (MIMICS(r), Materialise, Leuven, Belgium) is reported as very useful
software for evaluation of OPLL, but its reliability and reproducibility are
obscure. This study was conducted to evaluate the accuracy of MIMICS(r) system,
and inter- and intra-observer reliability in the measurement of OPLL. METHODS:
Three neurosurgeons independently analyzed the randomly selected 10 OPLL cases
with medical image processing software (MIMICS(r)) which create 3D model with
Digital Imaging and Communication in Medicine (DICOM) data from CT images after
brief explanation was given to examiners before the image construction steps. To
assess the reliability of inter- and intra-examiner intraclass correlation
coefficient (ICC), 3 examiners measured 4 parameters (volume, length, width, and
length) in 10 cases 2 times with 1-week interval. RESULTS: The inter-examiner
ICCs among 3 examiners were 0.996 (95% confidence interval [CI], 0.987-0.999) for
volume measurement, 0.973 (95% CI, 0.907-0.978) for thickness, 0.969 (95% CI,
0.895-0.993) for width, and 0.995 (95% CI, 0.983-0.999) for length. The intra
examiner ICCs were 0.994 (range, 0.991-0.996) for volume, 0.996 (range, 0.944
0.998) for length, 0.930 (range, 0.873-0.947) for width, and 0.987 (range, 0.985
0.995) for length. CONCLUSION: The medical image processing software (MIMICS(r))
provided detailed quantification OPLL volume with minimal error of inter- and
intra-observer reliability in the measurement of OPLL.
PMID- 28689394
TI - Magnetic Resonance Imaging Patterns of Post-Operative Spinal Infection:
Relationship between the Clinical Onset of Infection and the Infection Site.
AB - OBJECTIVE: To investigate the magnetic resonance imaging (MRI) findings and the
patterns of postoperative spinal infection according to the passage of time.
METHODS: Institutional review board approval was obtained, and informed consent
was not obtained for the retrospective review of patients' medical records. A
total of 43 patients (27 men and 16 women; mean age, 64) diagnosed with
postoperative spinal infection were included in this study. We retrospectively
reviewed the MRI findings and the medical records and categorized the infection
sites based on MRI, i.e., anterior, posterior, and both parts. The duration of
the clinical onset from surgery was divided, i.e., acute (<=2 weeks), subacute (2
4 weeks), and late (>4 weeks). RESULTS: Postoperative spinal infection was
involved in the posterior part in 31 (72%), anterior part in two (4.7%), and both
parts in 10 patients (23.3%). Abscess or phlegmon in the back muscles and
laminectomy site were the most common MRI findings. The number of patients with
acute, subacute, and late clinical onset were 35, two, and six, respectively
(mean, 33.4 days; range, 1-730 days). The mean duration of the clinical onset was
12 days in the posterior part, 15.2 days in both parts, and 456.5 days in the
anterior part. CONCLUSION: Postoperative spinal infection usually occurred within
four weeks in the posterior part and over time the infection was considered to
spread into the anterior part. For the evaluation of postoperative spinal
infection, the posterior surgical field was more important than the vertebral
body or the disc space on MRI.
PMID- 28689395
TI - Prognostic Factor Analysis for Management of Chronic Neck Pain: Can We Predict
the Severity of Neck Pain with Lateral Cervical Curvature?
AB - OBJECTIVE: Although little is known about its origins, neck pain may be related
to several associated anatomical pathologies. We aimed to characterize the
incidence and features of chronic neck pain and analyze the relationship between
neck pain severity and its affecting factors. METHODS: Between March 2012 and
July 2013, we studied 216 patients with chronic neck pain. Initially, combined
tramadol (37.5 mg) plus acetaminophen (325 mg) was administered orally twice
daily (b.i.d.) to all patients over a 2-week period. After two weeks, patients
were evaluated for neck pain during an outpatient clinic visit. If the numeric
rating scale of the patient had not decreased to 5 or lower, a cervical medial
branch block (MBB) was recommended after double-dosed previous medication trial.
We classified all patients into two groups (mild vs. severe neck pain group),
based on medication efficacy. Logistic regression tests were used to evaluate the
factors associated with neck pain severity. RESULTS: A total of 198 patients were
included in the analyses, due to follow-up loss in 18 patients. While medication
was successful in reducing pain in 68.2% patients with chronic neck pain, the
remaining patients required cervical MBB. Lateral cervical curvature, such as a
straight or sigmoid type curve, was found to be significantly associated with the
severity of neck pain. CONCLUSION: We managed chronic neck pain with a simple
pharmacological management protocol followed by MBB. We should keep in mind that
it may be difficult to manage the patient with straight or sigmoid lateral
curvature only with oral medication.
PMID- 28689396
TI - Correlation between MRI Grading System and Surgical Findings for Lumbar Foraminal
Stenosis.
AB - OBJECTIVE: Magnetic resonance imaging (MRI) grading systems using sagittal images
are useful for evaluation of lumbar foraminal stenosis. We evaluated whether such
a grading system is useful as a diagnostic tool for surgery. METHODS: Between
July 2014 and June 2015, 99 consecutive patients underwent unilateral lumbar
foraminotomy for lumbar foraminal stenosis. Surgically confirmed foraminal
stenosis and the contralateral, asymptomatic neuroforamen were assessed based on
a 4-point MRI grading system. Two experienced researchers independently evaluated
the MR sagittal images. Interobserver agreement and intraobserver agreement were
analyzed using kappa statistics. RESULTS: The mean age of patients (54 women, 45
men) was 62.5 years. A total of 101 levels (202 neuroforamens) were evaluated.
MRI grades for operated neuroforamens were as follows: Grade 0 in 0.99%, Grade 1
in 5.28%, Grade 2 in 14.85%, and Grade 3 in 78.88%. Interobserver agreement was
moderate for operated neuroforamens (kappa=0.511) and good for asymptomatic
neuroforamens (kappa=0.696). Intraobserver agreement by reader 1 for operated
neuroforamens was good (kappa=0.776) and that for asymptomatic neuroforamens was
very good (kappa=0.831). In terms of lumbar level, interobserver agreement for L5
S1 (kappa=0.313, fair) was relatively lower than the other level (kappa=0.804,
very good). CONCLUSION: MRI grading system for lumbar foraminal stenosis is
thought to be useful as a diagnostic tool for surgery in the lumbar spine;
however, it is less reliable for symptomatic L5-S1 foraminal stenosis than for
other levels. Thus, various clinical factors as well as the MRI grading system
are required for surgical decision-making.
PMID- 28689397
TI - Invention of the Guide Catheter Irrigation Monitoring Device for
Neuroendovascular Therapy.
AB - OBJECTIVE: The thromboembolic events during neuroendovascular therapy (NET) are
the major complications of concern that can be occasionally fatal. The thrombotic
occlusion of the guide catheter for NET is thought to be the risk of the
thromboembolic events. We have developed an idea for inventing the monitoring
system of the continuous irrigation through the guide catheter. We herein present
a unique invention of the guide catheter irrigation monitoring device. METHODS:
We have developed ideas for preventing the thrombotic occlusion of the guide
catheter. In order to design a convenient device working in the practical use, we
have consulted and shared the ideas with the electrical engineers about putting
the invention. RESULTS: The guide catheter irrigation monitoring device (GCIMD)
consisted of three parts of optical sensor, main body and electric adapter. In
brief, the basic principles of working of the GCIMD are as follows. The optical
sensor is attached to the dripping chamber of the line to irrigation solution.
The main body had the small light and speaker to make an alarm sounds. The sensor
monitors the dripping of flush solution. If the dripping stops more than three
seconds, a warning alarm has been activated. So, the operating physicians can
concentrate and check the guide catheter irrigation. After the use of the GCIMD,
there was no major thromboembolic complication in conjunction with the thrombotic
occlusion of the guide catheter in our institute. CONCLUSION: We have developed a
brilliant invention of the GCIMD for NET.
PMID- 28689398
TI - An Electrode Configuration for Recording Muscle Motor Evoked Potentials in the
Upper Extremities during Intraoperative Neurophysiological Monitoring.
AB - OBJECTIVE: The main aim of the present study is to examine the electrode
configurations used to record the muscle motor evoked potential (mMEP) in the
upper extremities during surgery with the goal of producing a high and stable
mMEP signal, in particular among the abductor pollicis brevis (APB), abductor
digiti minimi (ADM), and across the APB-ADM muscles, which have been widely used
for the mMEP in the upper extremities. METHODS: Thirty right-handed patients were
recruited in this prospective study. No patients showed any adverse events in
their mMEP signals of the upper extremities during surgery. The mMEPs were
recorded independently from the signals for the APB and ADM and for those across
the APB-ADM. RESULTS: The mMEP amplitude from across the APB-ADM was
statistically higher than those recorded from the APB and ADM muscles. Moreover,
the coefficient of variation of the mMEP amplitude from across the APB-ADM was
smaller than those of mMEP amplitude recorded from the APB and ADM muscles.
CONCLUSION: The mMEP from across the APB-ADM muscles showed a high yield with
high stability compared to those in each case from the APB and ADM muscles. The
configuration across the APB-ADM muscles would be best for mMEP recordings from
the upper extremities for intraoperative neurophysiological monitoring purposes.
PMID- 28689399
TI - Sphingomonas Paucimobilis: A Rare Infectious Agent Found in Cerebrospinal Fluid.
AB - Sphingomonas paucimobilis (S. paucimobilis) is a gram negative bacillus. It has
existed in soil, drinking water and plants. It has been isolated from distilled
water tanks, respirators, and hemodialysis devices at the hospital setting.
Patients with chronic disorders or immune suppression may be susceptible to
infections with it. This microorganism has also been reported to infect healthy
persons. Both nosocomial and community-acquired infections have been reported. So
far, a variety of infections have been reported, including sepsis, septic
pulmonary embolism, septic arthritis, peritonitis, and endophthalmitis. Only 2
cases of meningitis have been reported so far in the literature. So far, no
previous reports of culture proliferation have been reported in patients with
external ventricular drains, as was the case in our patient. Therefore, our case
is the first to have S. paucimobilis proliferation in cerebrospinal fluid culture
during intensive care unit stay for an external ventricular drain.
PMID- 28689400
TI - Comment on "Transient Conformational Changes of Sensory Rhodopsin II Investigated
by Vibrational Stark Effect Probes".
PMID- 28689402
TI - Purple Fibrils: A New Type of Protein Chromophore.
AB - A purple color is formed during the fibrillation of lysozyme, a well-studied
protein lacking a prosthetic group. The application of Raman spectroscopy,
electron paramagnetic resonance and UV-vis absorption spectroscopy indicates the
formation of a sulfur?pi-bonded radical cation due to the methionine
phenylalanine interaction, which is consistent with a small molecule model
reported in the literature. A purple chromophore with characteristic 550 nm
absorption is formed due to a specific orientation of the sulfur-centered radical
cation and a phenyl ring stabilized by the fibril framework. A specific fibril
conformation and the resulting formation of the chromophore are controlled
reversibly by varying the pH. This is the first known example of a side chain
self-assembled chromophore formed due to protein aggregation.
PMID- 28689401
TI - Hole Hopping through Tryptophan in Cytochrome P450.
AB - Electron-transfer kinetics have been measured in four conjugates of cytochrome
P450 with surface-bound Ru-photosensitizers. The conjugates are constructed with
enzymes from Bacillus megaterium (CYP102A1) and Sulfolobus acidocaldarius
(CYP119). A W96 residue lies in the path between Ru and the heme in CYP102A1,
whereas H76 is present at the analogous location in CYP119. Two additional
conjugates have been prepared with (CYP102A1)W96H and (CYP119)H76W mutant
enzymes. Heme oxidation by photochemically generated Ru3+ leads to P450 compound
II formation when a tryptophan residue is in the path between Ru and the heme; no
heme oxidation is observed when histidine occupies this position. The data
indicate that heme oxidation proceeds via two-step tunneling through a tryptophan
radical intermediate. In contrast, heme reduction by photochemically generated
Ru+ proceeds in a single electron tunneling step with closely similar rate
constants for all four conjugates.
PMID- 28689403
TI - Fast Hydrolysis Polyesters with a Rigid Cyclic Diol from Camphor.
AB - 2,2:3,3-Bis(4'-hydroxymethylethylenedioxy)-1,7,7-trimethylbicyclo[2.2.1]heptane,
abbreviated as CaG, is a compound obtained by transforming a ketone group to a
ketal group with camphorquinone and glycerol. The CaG diol has a complex and
rigid structure and two primary hydroxyl groups. A polyester series was
synthesized with the CaG diol, ethylene glycol, and dimethyl terephthalate. The
polyesters exhibited adequate thermal stability up to nearly 330 degrees C and
had a high Tg, which steadily increased from 78 to 129 degrees C as the content
of CaG increased. A high proportion of the CaG moiety led to an amorphous region
that is susceptible to hydrolysis and promoted degradation of the polyester in
acidic conditions. Depending on the proportion of CaG in the polymer, the
hydrolytic degradation of the polyesters was adjustable.
PMID- 28689405
TI - Quantitative Analysis of Human Red Blood Cell Proteome.
AB - Red blood cells (RBCs) are the most abundant cell type in the human body. RBCs
and, in particular, their plasma membrane composition have been extensively
studied for many years. During the past decade proteomics studies have extended
our knowledge on RBC composition; however, these studies did not provide
quantitative insights. Here we report a large-scale proteomics investigation of
RBCs and their "white ghost" membrane fraction. Samples were processed using the
multienzyme digestion filter-aided sample preparation (MED-FASP) and analyzed
using Q-Exactive mass spectrometer. Protein abundances were computed using the
total protein approach (TPA). The validation of the data with stable isotope
labeled peptide-based protein quantification followed. Our in-depth analysis
resulted in the identification of 2650 proteins, of which 1890 occurred at more
than 100 copies per cell. We quantified 41 membrane transporter proteins spanning
an abundance range of five orders of magnitude. Some of these, including the drug
transporter ABCA7 and choline transporters SLC44A1 and SLC44A2, have not
previously been identified in RBC membranes. Comparison of protein copy numbers
assessed by proteomics showed a good correlation with literature data; however,
abundances of several proteins were not consistent with the classical references.
Because we validated our findings by a targeted analysis using labeled standards,
our data suggest that some older reference data from a variety of biochemical
approaches are inaccurate. Our study provides the first "in-depth" quantitative
analysis of the RBC proteome and will promote future studies of erythrocyte
structure, functions, and disease.
PMID- 28689404
TI - Discovery of a Covalent Kinase Inhibitor from a DNA-Encoded Small-Molecule
Library * Protein Library Selection.
AB - We previously reported interaction determination using unpurified proteins
(IDUP), a method to selectively amplify DNA sequences encoding ligand:target
pairs from a mixture of DNA-linked small molecules and unpurified protein targets
in cell lysates. In this study, we applied IDUP to libraries of DNA-encoded
bioactive compounds and DNA-tagged human kinases to identify ligand:protein
binding partners out of 32 096 possible combinations in a single solution-phase
library * library experiment. The results recapitulated known small
molecule:protein interactions and also revealed that ethacrynic acid is a novel
ligand and inhibitor of MAP2K6 kinase. Ethacrynic acid inhibits MAP2K6 in part
through alkylation of a nonconserved cysteine residue. This work validates the
ability of IDUP to discover ligands for proteins of biomedical relevance.
PMID- 28689406
TI - Proteomic Analysis of Amyloid Corneal Aggregates from TGFBI-H626R Lattice Corneal
Dystrophy Patient Implicates Serine-Protease HTRA1 in Mutation-Specific
Pathogenesis of TGFBIp.
AB - TGFBI-associated corneal dystrophies are inherited disorders caused by TGFBI gene
variants that promote deposition of mutant protein (TGFBIp) as insoluble
aggregates in the cornea. Depending on the type and position of amino acid
substitution, the aggregates may be amyloid fibrillar, amorphous globular or
both, but the molecular mechanisms that drive these different patterns of
aggregation are not fully understood. In the current study, we report the protein
composition of amyloid corneal aggregates from lattice corneal dystrophy patients
of Asian origin with H626R and R124C mutation and compared it with healthy
corneal tissues via LC-MS/MS. We identified several amyloidogenic, nonfibrillar
amyloid associated proteins and TGFBIp as the major components of the deposits.
Our data indicates that apolipoprotein A-IV, apolipoprotein E, and serine
protease HTRA1 were significantly enriched in patient deposits compared to
healthy controls. HTRA1 was also found to be 7-fold enriched in the amyloid
deposits of patients compared to the controls. Peptides sequences
(G511DNRFSMLVAAIQSAGLTETLNR533 and Y571HIGDEILVSGGIGALVR588) derived from the
fourth FAS-1 domain of TGFBIp were enriched in the corneal aggregates in a
mutation-specific manner. Biophysical studies of these two enriched sequences
revealed high propensity to form amyloid fibrils under physiological conditions.
Our data suggests a possible proteolytic processing mechanism of mutant TGFBIp by
HTRA1 and peptides generated by mutant protein may form the beta-amyloid core of
corneal aggregates in dystrophic patients.
PMID- 28689407
TI - Direct Online Determination of Laser-Induced Particle Size Distribution by ICPMS.
AB - The characterization of the aerosol (size, composition, and concentration)
generated by Laser Ablation is of great interest due to its impact on the
analytical performances when coupled to Inductively Coupled Plasma Mass
Spectrometry (ICPMS). The capabilities of High Resolution ICPMS as a direct tool
to characterize nanoparticles produced by femtosecond Laser Ablation of pure
copper are presented. An analytical protocol, similar to the "single particle
ICPMS" technique used to characterize the size distribution of nanoparticles in
solution, was developed in order to observe the signals of individual particles
produced by a single ablation shot. A Visual Basic for Applications (VBA) data
processing was developed to count and sort the particles as a function of their
size and thus determine the particle size distribution. To check the reliability
of the method, the results were compared to a more conventional technique,
namely, Electrical Low Pressure Impaction (ELPI) for 4000 shots. Detection limit
for the particles produced by the laser ablation of a copper foil is of a few
attograms corresponding to a nanoparticle of 14 nm. The direct online
determination of particle size by ICPMS gave similar results than ELPI for copper
particles ejected during the ablation shot by shot at a fixed spot, from 1 to 100
shots. Particles larger than 159 nm represented less than 1% of the aerosol whose
distribution was centered on 25-51 nm.
PMID- 28689408
TI - Liquid-Liquid Phase Separation in Oligomeric Peptide Solutions.
AB - Oligomeric peptides exist widely in living organisms and play a role in a broad
range of biological functions. We report the first observation of liquid-liquid
phase separation (LLPS) in peptide solutions, in particular, solutions of
peptides consisting of noncovalent oligomers. We determined the binary phase
boundary of the oligomeric peptide solution and compared the result to the well
established phase diagram of globular proteins. We also provide simple
theoretical interpretations of the similarities and differences between the phase
diagrams of peptides and proteins. Finally, by tuning inter-oligomer interactions
using a crowding agent, we demonstrated that LLPS is a universal phenomenon that
can be observed under different solution conditions for a variety of peptides.
PMID- 28689410
TI - New Aromatic Compounds from the Fruiting Body of Sparassis crispa (Wulf.) and
Their Inhibitory Activities on Proprotein Convertase Subtilisin/Kexin Type 9 mRNA
Expression.
AB - Successive chromatography of EtOAc-soluble extracts of the fruiting body of
Sparassis crispa (Wulf.) resulted in isolation of four new aromatic compounds,
sparoside A (1) and sparalides A-C (3-5), two new naturally occurring compounds,
2 and 6, and eight known compounds, 7-14. The chemical structures were determined
by interpretation of nuclear magnetic resonance and mass spectrometry
spectroscopic data. Extract, solvent-soluble fractions of the extract, and all of
the pure compounds isolated from the fractions were subjected to the mRNA
expression assay for proprotein convertase subtilisin/kexin type 9 (PCSK9). Among
them, sparoside A (1), hanabiratakelide A (8), adenosine (11), and 5alpha,6alpha
epoxy-(22E,24R)-ergosta-8(14),22-diene-3beta,7beta-diol (14) exhibited potent
inhibitory activities on PCSK9 mRNA expression, with IC50 values of 20.07, 7.18,
18.46, and 8.23 MUM, respectively (berberine, positive control, IC50 = 8.04 MUM),
suggesting that compounds 1, 8, 11, and 14 are suitable for use in supplements to
the statins for hyperlipidemia treatments.
PMID- 28689409
TI - Global Phosphoproteomic Analysis of Insulin/Akt/mTORC1/S6K Signaling in Rat
Hepatocytes.
AB - Insulin resistance is a hallmark of type 2 diabetes. Although multiple genetic
and physiological factors interact to cause insulin resistance, deregulated
signaling by phosphorylation is a common underlying mechanism. In particular, the
specific phosphorylation-dependent regulatory mechanisms and signaling outputs of
insulin are poorly understood in hepatocytes, which represents one of the most
important insulin-responsive cell types. Using primary rat hepatocytes as a model
system, we performed reductive dimethylation (ReDi)-based quantitative mass
spectrometric analysis and characterized the phosphoproteome that is regulated by
insulin as well as its key downstream kinases including Akt, mTORC1, and S6K. We
identified a total of 12 294 unique, confidently localized phosphorylation sites
and 3805 phosphorylated proteins in this single cell type. Detailed bioinformatic
analysis on each individual data set identified both known and previously
unrecognized targets of this key insulin downstream effector pathway.
Furthermore, integrated analysis of the hepatic Akt/mTORC1/S6K signaling axis
allowed the delineation of the substrate specificity of several close-related
kinases within the insulin signaling pathway. We expect that the data sets will
serve as an invaluable resource, providing the foundation for future hypothesis
driven research that helps delineate the molecular mechanisms that underlie the
pathogenesis of type 2 diabetes and related metabolic syndrome.
PMID- 28689411
TI - Adsorption and Diffusion of C1 to C4 Alkanes in Dual-Porosity Zeolites by
Molecular Simulations.
AB - We employ grand canonical Monte Carlo and molecular dynamics simulations to
systematically study the adsorption and diffusion of C1 to C4 alkanes in
hierarchical ZSM-5 zeolite with micropores (~1 nm) and mesopores (>2 nm). The
zeolite is characterized by a large surface area of active sites on the
microporous scale with high permeability and access to the active sites, which
arises from the enhanced transport at the mesoporous scale. We model this zeolite
as a microporous Na+-exchanged alumino-sillicate zeolite ZSM-5/35 (Si/Al = 35) in
which cylindrical mesopores with a diameter of 4 nm have been built by deleting
atoms accordingly. We use the TraPPE and Vujic-Lyubartsev force fields along with
the Lorentz-Berthelot combining rules to describe adsorbate-adsorbate and
adsorbate-adsorbent interactions. The performance of the force fields is assessed
by comparing against experimental single-component adsorption isotherms of
methane and ethane in microporous ZSM-5/35, which we measured as part of this
work. We compare the adsorption isotherms and diffusivities of the adsorbed
alkanes in the dual-porosity zeolite with those in microporous ZSM-5/35 and
discern the specific behavior at each porosity scale on the overall adsorption,
self-diffusion, and transport behavior in zeolites with dual
micro/mesoporosities.
PMID- 28689413
TI - Mesoscopic Structures of Poly(carboxybetaine) Block Copolymer and Poly(ethylene
glycol) Block Copolymer in Solutions.
AB - The antifouling property of exogenous materials is vital for their in vivo
applications. In this work, dissipative particle dynamics simulations are
performed to study the self-assembled morphologies of two copolymer systems
containing poly(ethylene glycol) (PEG) and poly(carboxybetaine) (PCB) in aqueous
solutions. Effects of polymer composition and polymer concentration on the self
assembled structures of the two copolymers (PLA-PEG and PLA-PCB) are
investigated, respectively [PLA represents poly(lactic acid)]. Results show that
whatever the copolymer composition is, PLA-PEG systems will self-assemble into
core-shell structures, whereas onion-like and vesicle structures are also found
for the PLA-PCB systems. Different morphologies are obtained at different polymer
concentrations in both copolymer systems. Simulation results demonstrate that PCB
is more stable than PEG in maintaining self-assembled spherical structures of
copolymer systems because PLA-PEG forms dumbbell-like structures whereas PLA-PCB
is spherical under the same polymer concentration. Although both copolymer
systems can self-assemble into core-shell nanoparticles when the block ratio of
PLA:PEG or PLA:PCB is 80:20, the core-shell structures of the nanoparticles are
quite different. The shell layers formed by PEG in PLA-PEG nanoparticles are
inhomogeneous in size because of the amphiphilicity of PEG, whereas the shell
layers in PLA-PCB nanoparticles are homogenous because of the strong
hydrophilicity of the zwitterionic PCB polymer block.
PMID- 28689412
TI - Bexarotene Does Not Clear Amyloid Beta Plaques but Delays Fibril Growth:
Molecular Mechanisms.
AB - In 2012, it was reported that anticancer drug bexarotene reduced amyloid plaque
and improved mental functioning in a small sample of mice engineered to exhibit
Alzheimer's like symptoms. It has been suggested that bexarotene stimulates
expression of apolipoprotein E (ApoE) leading to intracellular clearance of
amyloid beta (Abeta). However, the effect of bexarotene on clearance of plaques
has not been seen in some mouse models. Two interesting questions include whether
bexarotene can destroy Abeta fibrils via direct interaction with them and how
this compound impacts the lag phase in the fibril growth process. By the
Thioflavin T fluorescence assay and atomic force microscopy, we have shown that
bexarotene prolongs the lag phase, but it does not degrade Abeta fibrils. The
impotence of bexarotene in destroying fibrils means that this compound is weakly
bound to Abeta. On the other hand, the weak binding would prevent bexarotene from
prolonging the lag phase. Thus, our two main in vitro observations seem to
contradict each other. In order to settle this problem at the atomic level, we
have performed all-atom molecular dynamics simulations in explicit water. We have
demonstrated that bexarotene is not capable to reduce amyloid deposits due to
weak binding to Abeta fibrils. However, it delays the self-assembly through
reduction of the beta-content of Abeta monomers at high enough ligand
concentrations. Bexarotene is the first compound which displays such an unusual
behavior. We have also shown that bexarotene has a low binding propensity to
Abeta monomer and dimer.
PMID- 28689415
TI - Thermophilic Enzyme or Mesophilic Enzyme with Enhanced Thermostability: Can We
Draw a Line?
AB - Aminoglycoside nucleotidyltransferase 4' (ANT) is a homodimeric enzyme that
modifies the C4'-OH site of aminoglycoside antibiotics by nucleotidylation. A few
single- and double-residue mutants of this enzyme (T130K, D80Y, and D80Y/T130K)
from Bacillus stearothermophilus show increased thermostability. This article
investigates how such residue replacements, which are distant from the active
site and monomer-monomer interface, result in various changes of the
thermostability of the enzyme. In this work, we show that the thermodynamic
properties of enzyme-ligand complexes and protein dynamics may be indicators of a
thermophilic behavior. Our data suggests that one of the single-site mutants of
ANT, D80Y, may be a thermophilic protein and the other thermostable mutant,
T130K, is actually a more heat-stable variant of the mesophilic wild type (WT)
with a higher Tm. Our data also suggest that T130K and D80Y adopt different
global dynamics strategies to achieve different levels of thermostability
enhancement and that the differences between the properties of the species can be
described in terms of global dynamics rather than in terms of specific structural
features. Thermophilicity of the D80Y comes at the cost of less favorable
thermodynamic parameters for ligand binding relative to WT. On the other hand,
the T130K species exhibits the same affinity to ligands and the same
thermodynamic parameters of complex formation as the WT enzyme. These
observations suggest that a quantitative characterization of ligand binding and
protein dynamics can be used to differentiate thermophilic proteins from their
simply more heat-stable mesophilic counterparts.
PMID- 28689414
TI - The Effects of Quinoline and Non-Quinoline Inhibitors on the Kinetics of Lipid
Mediated beta-Hematin Crystallization.
AB - The throughput of a biomimetic lipid-mediated assay used to investigate the
effects of inhibitors on the kinetics of beta-hematin formation has been
optimized through the use of 24-well microplates. The rate constant for beta
hematin formation mediated by monopalmitoyl-rac-glycerol was reduced from 0.17 +/
0.04 min-1 previously measured in Falcon tubes to 0.019 +/- 0.002 min-1 in the
optimized assay. While this necessitated longer incubation times, transferring
aliquots from multiple 24-well plates to a single 96-well plate for final
absorbance measurements actually improved the overall turnaround time per
inhibitor. This assay has been applied to investigate the effects of four
clinically relevant antimalarial drugs (chloroquine, amodiaquine, quinidine, and
quinine) as well as several short-chain 4-aminoquinoline derivatives and non
quinoline (benzamide) compounds on the kinetics of beta-hematin formation. The
adsorption strength of these inhibitors to crystalline beta-hematin (Kads) was
quantified using a theoretical kinetic model that is based on the Avrami equation
and the Langmuir isotherm. Statistically significant linear correlations between
lipid-mediated beta-hematin inhibitory activity and Kads values for quinoline (r2
= 0.76, P-value = 0.0046) and non-quinoline compounds (r2 = 0.99, P-stat =
0.0006), as well as between parasite inhibitory activity (D10) and Kads values
for quinoline antimalarial drugs and short-chain chloroquine derivatives (r2 =
0.64, P-value = 0.0098), provide a strong indication that drug action involves
adsorption to the surface of beta-hematin crystals. Independent support in this
regard is provided by experiments that spectrophotometrically monitor the direct
adsorption of antimalarial drugs to preformed beta-hematin.
PMID- 28689416
TI - Adaptive Splitting Integrators for Enhancing Sampling Efficiency of Modified
Hamiltonian Monte Carlo Methods in Molecular Simulation.
AB - The modified Hamiltonian Monte Carlo (MHMC) methods, i.e., importance sampling
methods that use modified Hamiltonians within a Hybrid Monte Carlo (HMC)
framework, often outperform in sampling efficiency standard techniques such as
molecular dynamics (MD) and HMC. The performance of MHMC may be enhanced further
through the rational choice of the simulation parameters and by replacing the
standard Verlet integrator with more sophisticated splitting algorithms.
Unfortunately, it is not easy to identify the appropriate values of the
parameters that appear in those algorithms. We propose a technique, that we call
MAIA (Modified Adaptive Integration Approach), which, for a given simulation
system and a given time step, automatically selects the optimal integrator within
a useful family of two-stage splitting formulas. Extended MAIA (or e-MAIA) is an
enhanced version of MAIA, which additionally supplies a value of the method
specific parameter that, for the problem under consideration, keeps the momentum
acceptance rate at a user-desired level. The MAIA and e-MAIA algorithms have been
implemented, with no computational overhead during simulations, in MultiHMC
GROMACS, a modified version of the popular software package GROMACS. Tests
performed on well-known molecular models demonstrate the superiority of the
suggested approaches over a range of integrators (both standard and recently
developed), as well as their capacity to improve the sampling efficiency of
GSHMC, a noticeable method for molecular simulation in the MHMC family. GSHMC
combined with e-MAIA shows a remarkably good performance when compared to MD and
HMC coupled with the appropriate adaptive integrators.
PMID- 28689417
TI - Synthesis and Study of Molecular Assemblies Formed by 4,6-O-(2-Phenylethylidene)
Functionalized d-Glucosamine Derivatives.
AB - Low-molecular-weight gelators are interesting small molecules with potential
applications as advanced materials. Carbohydrate-based small molecular gelators
are especially useful because they are derived from renewable resources and are
more likely to be biocompatible and biodegradable. Various 4,6-benzylidene acetal
protected alpha-methyl 2-d-glucosamine derivatives have been found to be
effective low-molecular-weight gelators. To understand the influence of the 4,6
benzylidene acetal functional group toward molecular self-assembly and to obtain
effective molecular gelators, we synthesized and analyzed a new series of d
glucosamine derivatives in which the phenyl group of the acetal is replaced by a
benzyl group. The homologation of the acetal protection from aromatic to
aliphatic functional groups allows us to probe the effect of increasing
structural flexibility on molecular self-assembly and gelation. In this study,
nine representative amides and nine urea analogs were synthesized, and their
gelation properties were analyzed in a series of organic solvents and aqueous
solutions. The resulting amide and urea derivatives are versatile organogelators
forming gels in toluene, ethanol, isopropanol, ethylene glycol, and aqueous
mixtures of organic solvents. More interestingly, the amide analogs are also
effective gelators for pump oil and engine oil. NMR spectroscopy at variable
temperatures was used to analyze the molecular assemblies and intermolecular
forces. The selected gelators with several drug and dye molecules in DMSO and
water were studied for their effectiveness of encapsulation and release of these
agents.
PMID- 28689418
TI - An Assay Based on SAMDI Mass Spectrometry for Profiling Protein Interaction
Domains.
AB - This paper describes an assay that can profile the binding of a protein to
ligands and can rank the affinities of a library of ligands. The method is based
on the enhanced rate of an enzyme-mediated reaction that follows from
colocalization of the enzyme and substrate by a protein-ligand interaction. This
assay uses a self-assembled monolayer that presents a candidate peptide ligand
for a receptor and a peptide substrate for an enzyme. The receptor is prepared as
a fusion to the relevant enzyme so that binding of the receptor to the
immobilized ligand brings the enzyme to the surface, where it can more rapidly
modify its substrate. The extent of conversion of the substrate to product is
therefore a measure of the average time the ligand-receptor complex is present
and is quantified using the SAMDI mass spectrometry technique. The approach is
used to profile the binding of chromodomain proteins to methylated lysine
peptides derived from the histone 3 protein. The relative affinities for the
peptide ligands found in this work agreed with results from prior studies.
Additionally, this work revealed cross-talk interactions whereby phosphorylation
of certain residues impaired binding of chromodomains to the peptide ligands. The
method presented here, which we term protein interaction by SAMDI (PI-SAMDI), has
the advantages that it is applicable to low-affinity interactions because the
complexes are not observed directly, but rather leave a "covalent record" of the
interaction that is measured with mass spectrometry and because it is compatible
with laboratory automation for high-throughput analysis.
PMID- 28689419
TI - Trifluoromethylation of Alkyl Radicals in Aqueous Solution.
AB - The copper-mediated trifluoromethylation of alkyl radicals is described. The
combination of Et3SiH and K2S2O8 initiates the radical reactions of alkyl
bromides or iodides with BPyCu(CF3)3 (BPy = 2,2'-bipyridine) in aqueous acetone
at room temperature to afford the corresponding trifluoromethylation products in
good yield. The protocol is applicable to various primary and secondary alkyl
halides and exhibits wide functional group compatibility. A mechanism involving
trifluoromethyl group transfer from Cu(II)-CF3 intermediates to alkyl radicals is
proposed.
PMID- 28689420
TI - Reply to "Comment on 'Transient Conformational Changes of Sensory Rhodopsin II
Investigated by Vibrational Stark Effect Probes'".
PMID- 28689421
TI - 2-Phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl 3-Oxide (PTIO*) Radical
Scavenging: A New and Simple Antioxidant Assay In Vitro.
AB - Current in vitro antioxidant assays have several limitations, which frequently
cause inconsistent results. The study develops a new antioxidant assay using the
2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide radical (PTIO*). After the
investigation of various factors, the experimental protocol was briefly
recommended as follows: PTIO* and the sample solution were added to phosphate
buffer (pH 7.4, 50 mM), incubated at 37 degrees C for 2 h, and then
spectrophotometrically measured at 557 nm. The validation test based on 20 pure
compounds and 30 lyophilized aqueous extracts suggested that PTIO* scavenging had
a good linear relationship, stability, and reproducibility. In the ultra
performance liquid chromatography coupled with electrospray ionization quadrupole
time-of-flight tandem mass spectrometry analysis, PTIO* was observed to give m/z
234 when encountering l-ascorbic acid. As an antioxidant assay, PTIO* scavenging
possesses four advantages, i.e., oxygen-centered radical, physiological aqueous
solution, simple and direct measurement, and less interference from the tested
sample. It can also satisfactorily analyze the antioxidant structure-activity
relationship. PTIO* scavenging has no stereospecificity and is at least involved
in H+ transfer.
PMID- 28689422
TI - Segmental intestinal necrosis in a young patient.
AB - Segmental ischemic colitis is an uncommon disease in young patients, being
usually associated to drug abuse, infectious or autoimmune diseases. We present a
case that, in spite of a complete diagnostic study, had repeatedly two attacks of
intestinal necrosis during his admission.
PMID- 28689423
TI - In response to the editorial: "Will societies of anesthesiologists partake in the
take-off of non-anesthesiologist administration of propofol?"
AB - The editorial of Dr. Dumonceau comments on the discrepancies with the
declarations done in regard to the article sent by titled Alvarez J. et al
"Safety of the patient in deep sedation for endoscopico digestive procedures". We
do not agree in the analysis of the mortality, with comparative studies between
anesthesiologists and not anesthesiologists and with the conclusion of the
editorial.
PMID- 28689424
TI - Epidemiology of inflammatory bowel disease in Malaga: incidence rate and follow
up of a cohort diagnosed between 2007-2008.
AB - BACKGROUND AND OBJECTIVES: The incidence of inflammatory bowel disease (IBD) in
Spain has been traditionally lower than in Northern European countries. Recent
epidemiological studies have found that these differences are diminishing. This
study estimates the incidence of IBD in Malaga (Spain), a city in Southern Spain
and relates its results to those found in our neighboring countries. MATERIAL AND
METHODS: This was a prospective study designed to collect new cases diagnosed
during the period from 2007-2008 and follow up these patients. Incidence is
expressed as number of patients per 100,000 population per year. The population
distribution found in the European Collaborative Study was used to standardize
incidence rates. RESULTS: The gross incidence rate of IBD in Malaga is 9/105, the
standardized incidence rate is 12.3/105 (9.7-15.6). CONCLUSIONS: These data are
similar to those found in our surroundings, although a higher incidence rate for
Crohn's disease (CD) as compared to ulcerative colitis (UC) was found. The
clinical characteristics and outcomes of our patients do not differ significantly
from those described for other populations.
PMID- 28689425
TI - Endoscopic retreatment of Zenker's diverticulum using novel endoscopic scissors -
The Clutch Cutter device.
AB - Treatment of Zenker's diverticulum by flexible endoscopy consists of the myotomy
of the cricopharyngeal muscle and is considered to be feasible, effective and
safe. This report describes the novel use of a Clutch Cutter(r) device to perform
flexible endoscopic retreatment of a symptomatic recurrence after previous
treatment using a Needle knife in a 68 year old woman with symptoms of dysphagia
for solids.
PMID- 28689426
TI - Enough discussions about who should use propofol in gastrointestinal endoscopy.
AB - Reflections in order to agree on who should be responsible for the deep sedation
with propofol in gastrointestinal endoscopies, after so many squabble between
anaesthesiologists and endoscopists.
PMID- 28689427
TI - Duodenal hematoma caused by endoscopic hemostatic procedures (sclerotherapy).
AB - Endoscopic hemostatic procedures such as local injection of epinephrine are
commonly used for the treatment of bleeding ulcers. Although the risks are
usually considered to be minimal, there are reports describing that duodenal
intramural hematomas may develop as a complication after endoscopy especially in
patients susceptible to hemorrhage such as those with anticoagulants therapy or
blood dyscrasia.
PMID- 28689428
TI - Long survival in a patient with metastatic colorrectal carcinoma: reality or
utopia?
AB - We report the case of a 42-year-old male patient with mucinous-type metastatic
colorectal carcinoma of eight years of evolution. He has received multiple lines
of cytostatic treatment with acceptable tolerance and without significant
impairment in his quality of life. At present, it is estimated that the overall
survival of metastatic colon cancer in cytostatic treatment is around 24 months.
However, a small subset of patients may present prolonged survivals of 5 to 10
years after diagnosis, revealing heterogeneity of tumor behavior and response to
treatment. Our clinical case represents a long survivor patient despite the
advanced stage of his oncological mucinous-colorrectal disease, endorsed in the
scientific literature as having worse rates of objective response and less
survival. There are different therapeutic approaches that can achieve a
significant overall survival. It is essential in clinical practice to use all
drugs available to achieve increase of progression-free survival and overall
survival, with maintenance of an adequate quality of life.
PMID- 28689429
TI - Erratum.
PMID- 28689430
TI - Current and future therapies for gout.
AB - INTRODUCTION: Gout is a common disease responsible for recurrent flares triggered
by the deposition of monosodium urate crystals secondary to longstanding
hyperuricaemia. The management of gout implies both the treatment of flares and
the treatment of hyperuricaemia itself. Recent improvement in the understanding
of the disease led to the development of new drugs. Areas covered: This review
covers data related to 'old' treatments of flares and hyperuricaemia, evidence on
the recently approved drugs and emerging therapies in development. Expert
opinion: Recent data provide a good grasp of the optimal use of colchicine,
corticosteroids and NSAIDs for the treatment of flares. Interleukin-1 blocking
therapies have an increasing role in the management of difficult-to-treat gout.
Sub-optimal use of allopurinol is common and its potency to reduce serum uric
acid (SUA) levels is underestimated. Febuxostat effectively reduces SUA levels.
New uricosurics, notably lesinurad and arhalofenate, in combination with xanthine
oxidase inhibitors, offer promising perspectives to help a greater number of
patients achieve sufficient SUA reduction.
PMID- 28689431
TI - What Is Known About the Psychodermatology Clinic Model of Care? A Systematic
Scoping Review.
AB - BACKGROUND: Psychodermatology focuses on the interaction between skin and mental
health. Existing research discusses the recognition and treatment of these
disorders. However, little is known about the operational structure of
subspecialised psychodermatology clinics. OBJECTIVE: To identify literature on
the structure and logistics of delivering a psychodermatology service. METHODS: A
systematic search of MEDLINE, PsycINFO, Embase, and Google Scholar was performed.
Articles were included if they discussed the concept and organisation of a
psychodermatology practice. RESULTS: We identified 693 studies; after screening
titles and abstracts, 35 full-text articles were assessed, and 17 were included
in the scoping review. Most articles discussed aspects of clinic organisation in
general; others discussed management of a clinic in the context of specific
diseases or made recommendations on incorporating psychotherapeutic techniques in
a solo practitioner setting. A weekly multidisciplinary clinic or resident
teaching clinic with joint dermatologist-psychiatrist consultation is the most
commonly reported model. Specifically, a stepped level of care approach is often
used, where patients in increasing level of distress are stratified to the
appropriate team of trained professionals. A corresponding curriculum to
supplement practitioners' knowledge is recommended. CONCLUSIONS: Various clinic
models have been described to provide specialised psychodermatology care in
specific settings. Research is needed to assess the impact of these
multidisciplinary models of care on patient outcomes and health care costs.
PMID- 28689432
TI - Metabolite profiling in early clinical drug development: current status and
future prospects.
PMID- 28689433
TI - Experimental and early investigational drugs for androgenetic alopecia.
AB - INTRODUCTION: Treatments for androgenetic alopecia constitute a multi-billion
dollar industry, however, currently available therapeutic options have variable
efficacy. Consequently, in recent years small biotechnology companies and
academic research laboratories have begun to investigate new or improved
treatment methods. Research and development approaches include improved
formulations and modes of application for current drugs, new drug development,
development of cell-based treatments, and medical devices for modulation of hair
growth. Areas covered: Here we review the essential pathways of androgenetic
alopecia pathogenesis and collate the current and emerging therapeutic strategies
using journal publications databases and clinical trials databases to gather
information about active research on new treatments. Expert opinion: We propose
that topically applied medications, or intra-dermal injected or implanted
materials, are preferable treatment modalities, minimizing side effect risks as
compared to systemically applied treatments. Evidence in support of new
treatments is limited. However, we suggest therapeutics which reverse the
androgen-driven inhibition of hair follicle signaling pathways, such as
prostaglandin analogs and antagonists, platelet-rich plasma (PRP), promotion of
skin angiogenesis and perfusion, introduction of progenitor cells for hair
regeneration, and more effective ways of transplanting hair, are the likely near
future direction of androgenetic alopecia treatment development.
PMID- 28689435
TI - Effect of molecular weight and ratio of poly ethylene glycols' derivatives in
combination with trehalose on stability of freeze-dried IgG.
AB - The influence of poly ethylene glycol (PEG) at different molecular weights (MWs)
and ratios was studied on the stability of freeze-dried immune globulin G (IgG).
PEGs (600-4000 Dalton) at concentrations of 0.5 and 5% W/V were applied in the
presence of 40 and 60% W/W of trehalose to prepare freeze-dried IgG formulations.
Size-exclusion chromatography, infra-red spectroscopy, differential scanning
calorimeter, and gel electrophoresis were performed to characterize lyophilized
samples. Pure IgG demonstrated the highest aggregation of 5.77 +/- 0.10% after
process and 12.66 +/- 0.50% as well as 44.69 +/- 0.50% upon 1 and 2 months of
storage at 45 degrees C, respectively. 5% W/V of PEGs 4000 in combination with
40% W/W trehalose, significantly suppressed aggregation, 0.05 +/- 0.01%, with
minimum aggregation rate constant of 0.32 (1/month). The integrity of IgG
molecules and secondary conformation were properly preserved in all formulations
comparing native IgG. It could be concluded that appropriate concentration and MW
of PEGs, prominently augmented stabilizing effect of trehalose on freeze-dried
antibody through inserting additional supportive mechanisms of actions.
PMID- 28689436
TI - What are the prospects of apolipoprotein profiling for cardiovascular disease?
PMID- 28689434
TI - Role of genetic testing in patients undergoing percutaneous coronary
intervention.
AB - INTRODUCTION: Variability in individual response profiles to antiplatelet
therapy, in particular clopidogrel, is a well-established phenomenon. Genetic
variations of the cytochrome P450 (CYP) 2C19 enzyme, a key determinant in
clopidogrel metabolism, have been associated with clopidogrel response profiles.
Moreover, the presence of a CYP2C19 loss-of-function allele is associated with an
increased risk of atherothrombotic events among clopidogrel-treated patients
undergoing percutaneous coronary interventions (PCI), prompting studies
evaluating the use of genetic tests to identify patients who may be potential
candidates for alternative platelet P2Y12 receptor inhibiting therapies
(prasugrel or ticagrelor). Areas covered: The present manuscript provides an
overview of genetic factors associated with response profiles to platelet P2Y12
receptor inhibitors and their clinical implications, as well as the most recent
developments and future considerations on the role of genetic testing in patients
undergoing PCI. Expert commentary: The availability of more user-friendly genetic
tests has contributed towards the development of many ongoing clinical trials and
personalized medicine programs for patients undergoing PCI. Results of pilot
investigations have shown promising results, which however need to be confirmed
in larger-scale studies to support the routine use of genetic testing as a
strategy to personalize antiplatelet therapy and improve clinical outcomes.
PMID- 28689437
TI - The effect of antiepileptic drugs on the kidney function and structure.
AB - INTRODUCTION: Long-term use of antiepileptic drugs (AEDs) is associated with
number of somatic conditions. Data from experimental, cross-sectional and
prospective studies have evidence for the deleterious effect of some AEDs on the
kidney. Areas covered: This review summarized the current knowledge of the effect
of AEDs on the kidney including evidence and mechanisms. Fanconi syndrome was
reported with valproate (VPA) therapy in severely disabled children with
epilepsy. Renal tubular acidosis and urolithiasis were reported with
acetazolamide, topirmate and zonisamide, drugs with carbonic anhydrase inhibition
properties. Increased levels of urinary N-acetyl-beta-D-glucosaminidase (NAG) to
urinary creatinine (U-NAG/UCr), urinary excretion of alpha1-micrglobulin, beta
galactosidase activity; and urinary malondialdehyde to creatinine (MDA/Cr),
markers of renal glomerular and tubular injury, were reported with chronic use of
some AEDs (VPA, carbamazepine and phenytoin). The mechanism(s) of kidney
dysfunction/injury induced by AEDs is unknown. Experimental and clinical studies
have shown that VPA induces oxidative stress, mitochondrial deficits, carnitine
deficiency and inflammation and fibrosis in renal tissue in mice and in vitro
studies. Expert commentary: It seems reasonable to monitor kidney function during
treating patients with epilepsy at high risk of kidney injury (e.g. on combined
therapy with more than one AED, severely disabled children, etc).
PMID- 28689438
TI - The cost and value of glioblastoma therapy.
PMID- 28689439
TI - Aerosolized liposomes with dipalmitoyl phosphatidylcholine enhance pulmonary
absorption of encapsulated insulin compared with co-administered insulin.
AB - OBJECTIVE: We have previously shown that aerosolized liposomes with dipalmitoyl
phosphatidylcholine (DPPC) enhance the pulmonary absorption of encapsulated
insulin. In this study, we aimed to compare insulin encapsulated into the
liposomes versus co-administration of empty liposomes and unencapsulated free
insulin, where the DPCC liposomes would serve as absorption enhancer.
SIGNIFICANCE: The present study provides the useful information for development
of noninvasive treatment of diabetes. METHODS: Co-administration of empty DPPC
liposomes and unencapsulated free insulin was investigated in vivo to assess the
potential enhancement in protein pulmonary absorption. Co-administration was
compared to DPPC liposomes encapsulating insulin, and free insulin. RESULTS: DPPC
liposomes enhanced the pulmonary absorption of unencapsulated free insulin;
however, the enhancing effect was lower than that of the DPPC liposomes
encapsulating insulin. The mechanism of the pulmonary absorption of
unencapsulated free insulin by DPPC liposomes involved the opening of epithelial
cell space in alveolar mucosa, and not mucosal cell damage, similar to that of
the DPPC liposomes encapsulating insulin. In an in vitro stability test, insulin
in the alveolar mucus layer that covers epithelial cells was stable. These
findings suggest that, although unencapsulated free insulin spreads throughout
the alveolar mucus layer, the concentration of insulin released near the
absorption surface is increased by the encapsulation of insulin into DPPC
liposomes and the absorption efficiency is also increased. CONCLUSION: We
revealed that the encapsulation of insulin into DPPC liposomes is more effective
for pulmonary insulin absorption than co-administration of DPPC liposomes and
unencapsulated free insulin.
PMID- 28689440
TI - Chemical Composition and Antimicrobial Activities of the Essential Oil From
Salvia mirzayanii Leaves.
AB - Resistance of many pathogens to available drugs is a global challenge and is
leading to growing interest in natural alternative products. In this study,
chemical composition and in vitro antibacterial and antifungal activities of the
essential oil from Salvia mirzayanii were investigated. The chemical constituents
of essential oil from S mirzayanii were analyzed by gas chromatography-mass
spectrometry. The antimicrobial activity was determined by broth microdilution.
The main identified compounds were 1,8-cineole (41.2 +/- 1.3%), linalool acetate
(11.0 +/- 0.5%), and alpha-terpinyl acetate (6.0 +/- 0.4%) (mL of essential oil/g
of plant material). The MIC95 were 0.03 to 0.5 uL/mL and 16 to 128 uL/mL for gram
positive and gram-negative bacteria, respectively. These results indicated that
Salvia mirzayanii essential oil significantly inhibited the growth of standard
and clinically isolated tested yeasts by MIC50 0.03 to 1 uL/mL. Potent
antibacterial and antifungal activities of Salvia mirzayanii essential oil may be
considered in future study, particularly against antibiotic-resistant cases.
PMID- 28689441
TI - Update of sarilumb to treat rheumatoid arthritis based on randomized clinical
trials: a systematic review.
AB - INTRODUCTION: Sarilumab is a human monoclonal antibody against Interleukin 6
alpha (IL-6alpha) receptor. Compared to tocilizumab, another IL-6 alpha receptor
antibody, sarilumab has a different structure and higher affinity. Areas covered:
In a systematic literature review, we examined all sarilumab randomized clinical
trials (RCTs) in rheumatoid arthritis. The 6 reviewed RCTs included patients who
were inadequate MTX, DMARD and/or TNFi responders. Sarilumab 150-200 mg every 2
weeks improved RA signs, symptoms, function and decreased radiological
progression up to 52 weeks. The most common adverse events were infections and
neutropenia, the latter of which will require careful observation in future
trials. Examination of the effect of sero-positivity, disease duration, presence
of erosions, use of previous biologic and comparisons to other biologics etc are
still needed to complete understanding of this drug's profile. Long term studies,
too, will be needed to assess long term tolerability Expert commentary: Results
support the use of sarilumab to treat RA patients with inadequate response to
MTX, other DMARDs and TNFis, although further studies are needed to fully assess
its toxicity and understand the specific place of sarilumab in the RA
armamentarium.
PMID- 28689442
TI - Drug interactions in HIV-infected patients treated for hepatitis C.
AB - INTRODUCTION: The introduction of direct-acting antivirals (DAA) has
revolutionized the hepatitis C field. Most hepatitis C patients can now be cured,
including those coinfected with HIV. However, drug-drug interactions (DDI)
between DAA and antiretrovirals (ARV) should be known to prevent either toxicity
due to drug overexposure or treatment failures due to low drug concentrations.
Areas covered: Clinically significant DDI may be classified as major (when co
administration should be contraindicated) or minor (when they require close
monitoring, changes in drug dosage or in timing). Strategies for preventing and
managing DDI influence response rates in HIV/HCV-coinfected patients.
Pharmacokinetic evidence of interactions from clinical trials and reports from
real-world experience are discussed. Expert opinion: The most frequent DDI
between DAA and ARV affect drug metabolism by CYP450 induction/inhibition,
leading to abnormal drug exposures. Throughout this mechanism interact HCV and
HIV boosted protease inhibitors, and most non-nucleoside HCV and HIV polymerase
inhibitors. In contrast, HIV and HCV nucleos(t)ide analogue polymerase
inhibitors, most HCV NS5A inhibitors and HIV integrase inhibitors (e.g.,
dolutegravir), do not or only marginally affect CYP450, and therefore are
relatively free of DDI. Exposure to some HIV and HCV nucleos(t)ide analogues
(e.g., tenofovir and sofosbuvir, respectively) is subject to induction/inhibition
of drug transporters (e.g., P-glycoprotein) and requires special attention in
patients with renal insufficiency.
PMID- 28689443
TI - Does having a gastrectomy delay time to feeding and prolong hospital stay in
patients undergoing cytoreductive surgery and hyperthermic intraperitoneal
chemotherapy?
AB - AIM: Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy
(HIPEC) is routinely used to treat selected patients with peritoneal
carcinomatosis, but can be associated with prolonged hospital stay, significant
morbidity and mortality. Our objective was to assess whether patients undergoing
gastrectomy as part of CRS/HIPEC were at increased risk of delayed feeding time
and prolonged hospital stay. METHODS: Two hundred and fourteen consecutive
patients with peritoneal carcinomatosis treated with CRS/HIPEC between 2001 and
2016 were stratified by whether CRS included gastrectomy (n = 19, 9%) and
compared. Primary outcomes were time to full feeds and rate of serious morbidity
(Clavien-Dindo grades III-V). Secondary outcomes were durations of ICU and
hospital stays. RESULTS: Of 214 patients undergoing CRS/HIPEC, those undergoing
gastrectomy (19, 8.9%) had increased time to full feeds (8 vs. 5 days, p < 0.01),
and duration of ICU (2 vs. 1 days, p < 0.01) and total hospital stays (16 vs. 14
days, p = 0.013). There was no significant increase in serious complications,
although increased risk of pneumonia was noted (21% vs. 4.1%, p = 0.011).
Undergoing gastrectomy was not independently prognostic in multivariable analysis
including high peritoneal tumour load (PCI >12), multiple CRS procedures (number
>2) and operation duration (>480 min) in which operative duration remained
independently prognostic (p < 0.01). CONCLUSIONS: After surgery, early oral
refeeding may be beneficial in the majority of patients undergoing CRS/HIPEC.
However, patients found to have high peritoneal tumour load with extended surgery
and those who underwent gastrectomy should be considered for early post-operative
TPN due to the significant risk of delayed time to full feeds.
PMID- 28689444
TI - Ethnic variations on gestational diabetes mellitus and evidence-based first-line
interventions.
AB - PURPOSE/OBJECTIVES: To analyze the cultural and ethnic impact of gestational
diabetes mellitus (GDM), report the associated complications, and investigate how
lifestyle interventions are effective in preventing these associated
complications. METHODS: A literature review was conducted using online databases
like CINAHL and Cochrane review. Findings were limited to journal articles
published between 2012 and 2017. Irrelevant and relevant articles were determined
by research topic, specific population, and type of interventions. RESULTS: Due
to the growing rate of Hispanics, this ethnic group will have the most impact of
GDM. There is a link between the prevalence of GDM and being classified as obese
or overweight among women of childbearing age. Differences in perinatal outcomes
were noted in different ethnicities especially between Hispanic and Caucasian
women. Higher prevalence of GDM did not equal higher impact. In fact, the
ethnicity with the highest rate tends to have the lowest impact. Lifestyle
interventions reduced the rate and impact of complications of GDM. CONCLUSIONS:
There is ethnic variation on the impact of GDM, with the Hispanic women having
the most prevalence. Lifestyle interventions such as diet and exercise should be
the first-line therapy for all women with GDM.
PMID- 28689446
TI - Why isn't war properly framed and funded as a public health problem?
PMID- 28689445
TI - Abundance matters: role of albumin in diabetes, a proteomics perspective.
AB - INTRODUCTION: Human serum albumin (HSA) is a multifaceted protein with vital
physiological functions. It is the most abundant plasma protein with inherent
capability to bind to diverse ligands, and thus susceptible to various post
translational modifications (PTMs) which alter its structure and functions. One
such PTM is glycation, a non-enzymatic reaction between reducing sugar and
protein leading to formation of heterogeneous advanced glycation end products
(AGEs). Glycated albumin (GA) concentration increases significantly in diabetes
and is implicated in development of secondary complications. Areas covered: In
this review, we discuss in depth, formation of GA and its consequences,
approaches used for characterization and quantification of GA, milestones in GA
proteomics, clinical relevance of GA as a biomarker, significance of maintaining
abundant levels of albumin and future perspectives. Expert commentary: Elevated
GA levels are associated with development of insulin resistance as well as
secondary complications, in healthy and diabetic individuals respectively. Mass
spectrometry (MS) based approaches aid in precise characterization and
quantification of GA including early and advanced glycated peptides, which can be
useful in prediction of the disease status. Thus GA has evolved to be one of the
best candidates in the pursuit of diagnostic markers for prediction of
prediabetes and diabetic complications.
PMID- 28689447
TI - Specificity of peer difficulties to social anxiety in early adolescence:
categorical and dimensional analyses with clinical and community samples.
AB - BACKGROUND AND OBJECTIVES: We investigated the specificity of social difficulties
to social anxiety by testing associations of social anxiety and other anxiety
presentations with peer acceptance and victimization in community and treatment
seeking samples of adolescents aged 12-14 years. DESIGN: Cross-sectional,
quantitative survey. METHODS: Adolescents from the community (n = 116) and a
clinical setting (n = 154) completed ratings of anxiety symptoms, perceived
social acceptance, and peer victimization. Their parents also completed ratings
of the adolescents' anxiety and social acceptance. RESULTS: Social acceptance was
lowest among adolescents with social anxiety disorder (SAD) and lower among
adolescents with other anxiety disorders than in the community sample. Anxiety
symptoms were negatively correlated with social acceptance, but these
associations were not unique to social anxiety symptoms. Girls in the community
sample reported more overt victimization than girls with SAD and with other
anxiety diagnoses. Relational victimization was associated with social and
nonsocial anxiety symptoms only in the community sample. CONCLUSIONS: Our
findings supplement recent laboratory-based observational studies on social
functioning among adolescents with SAD and other anxiety disorders. Although
social anxiety may be associated with unique social skill deficits and
impairment, concerns about peer relations should also be considered among
adolescents with other anxiety symptoms.
PMID- 28689448
TI - Metastatic Melanoma in Sentinel Node-Negative Patients: The Ottawa Experience.
AB - BACKGROUND: Lymph node involvement is a major independent prognostic factor for
survival in patients with malignant melanoma. Sentinel lymph node biopsy (SLNB)
detection of microscopic nodal melanoma has been shown to improve both 5-year
survival and 5-year disease-free survival. OBJECTIVE: To determine the rate of
metastatic melanoma in SLNB-negative patients at long-term follow-up. METHODS:
Study subjects include all 152 patients who had a negative SLNB and were followed
at the Ottawa Regional Cancer Centre (ORCC) between 1999 and 2004. Patients with
a follow-up period less than 6 months, more than 1 primary melanoma, and
metastatic melanoma at diagnosis were excluded. Age at diagnosis, sex, Breslow
thickness, ulceration, mitoses, regression, Clark level, anatomical location,
development of metastatic melanoma, time to detection of metastatic disease, and
time to death from melanoma were studied. RESULTS: In this retrospective study at
the ORCC, 40 of 140 (28.6%) patients with a single primary melanoma developed
metastatic melanoma following negative SLNB at a mean follow-up of 63 months.
CONCLUSION: The rate of metastatic melanoma following negative SLNB at long-term
follow-up at the ORCC is higher than the upper limit of rates reported in the
literature (6%-24%). The reason for this is multifactorial, and the long follow
up period of 5 years allowed for detection of metastatic disease at a mean of 3.9
years. Long-term prognosis may be guarded in node-negative patients with a
primary cutaneous melanoma, and surveillance by a multidisciplinary team is
crucial.
PMID- 28689449
TI - Evaluating an Adjunctive Mobile App to Enhance Psychological Flexibility in
Acceptance and Commitment Therapy.
AB - The primary aims of this study were to evaluate the feasibility and potential
efficacy of a novel adjunctive mobile app designed to enhance the acquisition,
strengthening, and generalization of acceptance and commitment therapy (ACT)
skills being taught in therapy. A sample of 14 depressed/anxious clients
receiving ACT used the ACT Daily app for 2 weeks in a pre-post, open trial
design. Participants reported a high degree of program satisfaction. Clients
significantly improved over the 2-week period on depression and anxiety symptoms
as well as a range of psychological inflexibility measures. Analyses of mobile
app data indicated effects of ACT Daily skill coaching on in-the-moment measures
of inflexibility and symptoms, with unique effects found for acceptance and
mindfulness. Adjunctive ACT mobile apps appear promising in enhancing therapy
effects on psychological inflexibility and outcomes. A tailored skill coaching
approach like ACT Daily based on randomly prompted assessments may be especially
promising.
PMID- 28689450
TI - Recent advances and clinical insights into the use of proteomics in the study of
atherosclerosis.
AB - INTRODUCTION: The application of new proteomics methods may help to identify new
diagnostic/predictive molecular markers in an attempt to improve the clinical
management of atherosclerosis. Areas covered: Technological advances in
proteomics have enhanced its sensitivity and multiplexing capacity, as well as
the possibility of studying protein interactions and tissue structure. These
advances will help us better understand the molecular mechanisms at play in
atherosclerosis as a biological system. Moreover, this should help identify new
predictive/diagnostic biomarkers and therapeutic targets that may facilitate
effective risk stratification and early diagnosis, with the ensuing rapid
implementation of treatment. This review provides a comprehensive overview of the
novel methods in proteomics, including state-of-the-art techniques, novel
biological samples and applications for the study of atherosclerosis. Expert
commentary: Collaboration between clinicians and researchers is crucial to
further validate and introduce new molecular markers to manage atherosclerosis
that are identified using the most up to date proteomic approaches.
PMID- 28689451
TI - Tailoring therapy for ischemic cardiomyopathy: is Laplace's law enough?
AB - The burden of heart failure has long plagued the productive years of the
population, with therapeutic advances in the timely treatment of ischemic heart
disease decreasing its associated mortality. Angiotensin-converting enzyme
inhibitors and beta-blockers have impacted heart failure therapeutics in a
revolutionary way. The importance of blockade of the renin-angiotensin system and
adrenergic stimulation are fully accepted concepts that apply in young and old,
symptomatic and asymptomatic, borderline low and very low Ejection Fraction (EF),
left ventricular failure and biventricular failure. Despite several
interventions, both pharmaceutical and device based for the treatment of ensuing
heart failure, the incidence is increasing in large proportions. Newer molecules
like sacubitril show more promise. Despite these novel therapies, several
patients relentlessly progress to a stage of advanced heart failure. The use of
left-ventricular-assist devices has variable clinical benefit, with some patients
progressing to heart transplantation.
PMID- 28689452
TI - Using Bayesian statistics in health psychology: a comment on Depaoli et al.
(2017).
PMID- 28689454
TI - Identification and characterization of human UDP-glucuronosyltransferases
responsible for xanthotoxol glucuronidation.
AB - 1. Xanthotoxol is a furanocoumarin that possesses many pharmacological activities
and in this study its in vitro glucuronidation was studied. 2. Xanthotoxol can be
rapidly metabolized to a mono-glucuronide in both human intestine microsomes
(HIM) and human liver microsomes (HLM); the structure of the metabolite was
confirmed by NMR spectroscopy. 3. Reaction phenotyping with 12 commercial
recombinant human UGTs, as well as with the Helsinki laboratory UGT1A10 that
carry a C-terminal His-tag (UGT1A10-H), revealed that UGT1A10-H catalyzes
xanthotoxol glucuronidation at the highest rate, followed by UGT1A8. The other
enzymes, namely UGT1A3, UGT1A1, UGT1A6, UGT1A10 (commercial), and UGT2B7
displayed moderate-to-low reaction rates. 4. In kinetic analyses, HIM exhibited
much higher affinity for xanthotoxol, along with high Vmax and mild substrate
inhibition, whereas the kinetics in HLM was biphasic. UGT1A1 (high Km value),
UGT1A10-H (low Km value), and UGT1A8 exhibited mild substrate inhibition. 5.
Considering the above findings and the current knowledge on UGTs expression in
HIM, it is likely that UGT1A10 is mainly responsible for xanthotoxol
glucuronidation in the human small intestine, with some contribution from UGT1A1.
In the liver, this reaction is mainly catalyzed by UGT1A1 and UGT2B7. 6.
Glucuronidation appears to be the major metabolic pathway of xanthotoxol in
human.
PMID- 28689453
TI - Switching to the single-tablet regimen of elvitegravir, cobicistat,
emtricitabine, and tenofovir DF from non-nucleoside reverse transcriptase
inhibitor plus coformulated emtricitabine and tenofovir DF regimens: Week 96
results of STRATEGY-NNRTI.
AB - BACKGROUND: HIV-1-infected, virologically suppressed adults wanting to simplify
or change their non-nucleoside reverse transcriptase inhibitor (NNRTI)-based
regimens may benefit from switching to the single-tablet regimen of elvitegravir,
cobicistat, emtricitabine, and tenofovir disoproxil fumarate (E/C/F/TDF).
OBJECTIVE: We examined differences in the proportion of participants with HIV-1
RNA < 50 copies/mL (Snapshot analysis), change in CD4 cell count, safety, and
patient-reported outcomes in participants switching to E/C/F/TDF from an NNRTI +
FTC/TDF (TVD) regimen. METHODS: STRATEGY-NNRTI was a 96-week, phase 3b,
randomized, open-label, study examining the efficacy, safety, and tolerability of
switching to E/C/F/TDF in virologically suppressed individuals (HIV-1 RNA < 50
copies/mL) on an NNRTI + TVD regimen. Participants were randomized to switch or
remain on their NNRTI-based regimen (no-switch). RESULTS: At Week 96, 87%
(251/290) of switch and 80% (115/143) of no-switch participants maintained HIV-1
RNA < 50 copies/mL (difference 6.1%; 95% CI -1.3 to 14.2%; p = 0.12) according to
the FDA-defined snapshot algorithm. Both groups had similar proportions of
subjects with virologic failure (2.8% switch, 1.4% no-switch). Discontinuations
resulting from adverse events were infrequent (3% [9/291] switch, 2% [3/143] no
switch). Three switch participants (1%) discontinued due to renal adverse events
(2 of the 3 before Week 48). Switch participants reported significant
improvements in neuropsychiatric symptoms by as early as Week 4, and which were
maintained through Week 96. CONCLUSIONS: E/C/F/TDF is safe and effective and
reduces NNRTI-associated neuropsychiatric symptoms for virologically suppressed
HIV-positive adults switching from an NNRTI plus FTC/TDF-based regimen.
PMID- 28689455
TI - Human Papillomavirus Vaccine and Postural Orthostatic Tachycardia Syndrome: A
Review of Current Literature.
AB - The human papillomavirus (HPV) vaccine is efficacious in preventing complications
of human papillomavirus infection including cervical cancer. However, there have
been case reports of adverse events occurring after vaccination, one being
postural orthostatic tachycardia syndrome (POTS). This article reviews published
data and other available information regarding the relationship between the human
papillomavirus vaccine and POTS. Background information is provided regarding the
human papillomavirus vaccine and the proposed post-vaccination adverse event
POTS. Peer-reviewed literature, statements by government and medical advisory
committees, and publicly available information published on this topic are
examined. At this time, there is no conclusive evidence supporting a causal
relationship between the human papillomavirus vaccine and POTS. Though a causal
relationship has been postulated, it is of utmost importance to recognize that
while temporal associations may be observed, conclusions of causality cannot be
drawn from case reports and case series due to the small sample size and lack of
control population.
PMID- 28689456
TI - Chest Deformity and Disability due to Tenofovir-Induced Hypophosphatemic
Osteomalacia: Case Report and Call for Improved Global Access to Laboratory
Testing.
AB - Millions of people worldwide take tenofovir disoproxil fumarate (TDF) for the
treatment of human immunodeficiency virus (HIV) and/or hepatitis B infection.
Although generally safe and well tolerated, clinicians need to be aware that TDF
can cause proximal renal tubular dysfunction and loss of bone mineral density,
especially in patients with concomitant renal disease or other risk factors. We
present the case of a patient with chronic HIV infection and urethral stricture
who developed TDF-related proximal renal tubular dysfunction with
hypophosphatemia and osteomalacia, presenting with bone pains, skeletal
deformity, and disability. We review risk factors for TDF-related renal tubular
toxicity and recommendations for monitoring creatinine, phosphate, alkaline
phosphatase, and urinalysis.
PMID- 28689457
TI - Survey on acrylamide in roasted coffee and barley and in potato crisps sold in
Italy by a LC-MS/MS method.
AB - A survey on the occurrence of acrylamide (AA) in roasted coffee, barley, and
potato crisps was carried out using an intra-lab validated liquid chromatography
(LC)-MS (mass spectrometry)/MS method. Over the years 2015-2016, 66 samples of
coffee, 22 of roasted barley, and 22 of potato crisps were collected from retail
outlets in Italy. AA was detected in almost all samples. In roasted coffee, the
level exceeded 450 ug kg-1, the limit recommended by the European Commission
(EC), in 36.4% of the samples. In roasted barley, mean contamination was slightly
lower than in coffee and no sample exceeded the EC limit of 2000 ug kg-1. The AA
contamination in potato crisps was remarkable. A percentage of 36.4 (n = 8)
showed a value higher than the EC limit of 1000 ug kg-1. Considering the average
consumption of coffee and potato crisps by Italian people, AA exposure is
significant and should be decreased.
PMID- 28689458
TI - Marmoset pulmonary cytochrome P450 2F1 oxidizes biphenyl and 7-ethoxycoumarin and
hepatic human P450 substrates.
AB - 1. A potentially useful animal model for preclinical studies is the common
marmoset (Callithrix jacchus). In this study, using reverse-transcription
polymerase chain reaction from marmoset livers, we identified a novel cytochrome
P450 (P450) 2F1 cDNA with an open reading frame of 1473 bp. 2. High sequence
identities of 92-94% with primate P450 2 F amino acid sequences were indicated by
deduced amino acid sequences of P450 2F1 cDNA. Phylogenetic analysis indicates
that marmoset P450 2F1 is more congruent with primate P450 2 F forms than those
of other species such as rodents. 3. Among five tissue types examined, abundant
expression of marmoset P450 2F1 mRNA and P450 2F1 protein in lungs was shown.
Cynomolgus monkey P450 2F1 mRNA was abundantly expressed in lungs as well as
testes and ovaries in 10 tissue types. 4. Similar to those of humans and
cynomolgus monkeys, marmoset P450 2F1 heterologously expressed in Escherichia
coli membranes efficiently catalyzed 7-ethoxycoumarin O-deethylation and biphenyl
hydroxylation, however unlike human P450 2F1, marmoset P450 2F1 exhibited
hydroxylation activity toward coumarin and chlorzoxazone. 5. These findings
indicated that P450 2F1 enzyme expressed in marmoset lungs and also catalyzed
metabolism of xenobiotics, suggesting the importance of P450 2 F-dependent drug
metabolism in marmoset lungs.
PMID- 28689459
TI - Biomechanical comparison of supraacetabular external fixation and anterior pelvic
bridge plating.
AB - Unstable pelvic ring injuries are complex and risky injuries due to high
morbidity and mortality. Although anterior pelvic external fixator is a suitable
method for rapid stabilization of an injured pelvic ring, due to some
disadvantages such as high complication rate, nerve damage, and difficulties of
patient's mobility and comfort, there has recently been increased searching for
alternative methods for stabilization of the pelvic ring. Pubic symphysis zone
freely moves in pelvic models. This study aims to evaluate the biomechanical
stability of anterior pelvic bridge plating and compare it with supraacetabular
external fixators in an untreated unstable pelvic fracture model. Samples were
loaded statically with 2-mm/min loading rate in single leg standing position.
Maximum load was 2.3 kN. When loading the samples, photographs were taken
continuously. Stiffness values were calculated from the load displacement curves.
Some reference parameters were described and were measured from unloaded and 2.3
kN-loaded photographs of the test. The mean stiffness values were 491.14 +/-
52.22, 478.55 +/- 41.44, and 470.25 +/- 44.51 N/mm for anterior pelvic bridge
plating group, supraacetabular external fixator group, and Control group,
respectively. According to the measured parameters from photographs, the mean
displacement at the pubic symphysis was 4.7 +/- 0.32, 15.8 +/- 2.01, and 18.2 +/-
0.47 mm for anterior pelvic bridge plating, supraacetabular external fixator, and
Control group, respectively. The highest displacement in the pubic symphysis was
found in Control group, and minimum displacement was observed in anterior pelvic
bridge plating group. When the perpendicular distance between the right and left
lower end of ischium was examined, it was observed that displacement was minimum
in anterior pelvic bridge plating group compared to other two groups, regarding
to the high stability of pubic symphysis. In conclusion, this study revealed
superiority of anterior subcutaneous plate fixation with biomechanical results.
PMID- 28689460
TI - Global Threats From Preventable Injuries.
AB - Preventable injuries kill thousands of the world's population every day and
injure millions each year. Road traffic crashes and opioid drug misuse are major
causes of these injuries. Increased efforts are needed to promote strong
policies, develop new prevention strategies, and protect workers from these
global public health threats.
PMID- 28689461
TI - Factors associated with child passenger motorcycle helmet use in Cambodia.
AB - This study examines factors associated with child passenger helmet use in five
Cambodian provinces. We performed an analysis of periodic roadside observations
of helmet use over a four-year period. A total of 62,039 child passengers 12
years of age and younger met inclusion criteria and were included in the
analysis. Overall, 1369 (2.1%) of child passengers were observed to be wearing a
helmet. Most significantly, children were six times more likely to wear a helmet
if the driver was wearing a helmet (OR 6.2; 95% CI 5.1-7.5). In addition, the
odds of helmet use were noted to be significantly different depending on
province, day of the week, time of day and number of passengers on the
motorcycle. This study highlights the extremely low rate of child passenger
helmet use in Cambodia, and provides priorities for interventions and enforcement
to ensure all children are protected from head injury.
PMID- 28689462
TI - Measuring working memory load effects on electrophysiological markers of
attention orienting during a simulated drive.
AB - Intersection accidents result in a significant proportion of road fatalities, and
attention allocation likely plays a role. Attention allocation may depend on
(limited) working memory (WM) capacity. Driving is often combined with tasks
increasing WM load, consequently impairing attention orienting. This study (n =
22) investigated WM load effects on event-related potentials (ERPs) related to
attention orienting. A simulated driving environment allowed continuous lane
keeping measurement. Participants were asked to orient attention covertly towards
the side indicated by an arrow, and to respond only to moving cars appearing on
the attended side by pressing a button. WM load was manipulated using a
concurrent memory task. ERPs showed typical attentional modulation (cue:
contralateral negativity, LDAP; car: N1, P1, SN and P3) under low and high load
conditions. With increased WM load, lane-keeping performance improved, while dual
task performance degraded (memory task: increased error rate; orienting task:
increased false alarms, smaller P3). Practitioner Summary: Intersection driver
support systems aim to improve traffic safety and flow. However, in-vehicle
systems induce WM load, increasing the tendency to yield. Traffic flow reduces if
drivers stop at inappropriate times, reducing the effectiveness of systems.
Consequently, driver-support systems could include WM load measurement during
driving in the development phase.
PMID- 28689463
TI - Electroencephalogram Theta/Beta Ratio and Spectral Power Correlates of Executive
Functions in Children and Adolescents With AD/HD.
AB - OBJECTIVE: The electroencephalogram (EEG) has been widely used in AD/HD research.
The current study firstly aimed to replicate a recent trend related to EEG
theta/beta ratio (TBR) in children and adolescents. Also, the study aimed to
examine the value of resting EEG activity as biomarkers for executive function
(EF) in participants with AD/HD. METHOD: Fifty-three participants with AD/HD and
37 healthy controls were recruited. Resting EEG was recorded with eyes closed.
Participants with AD/HD additionally completed EF tasks via the Cambridge
Neuropsychological Test Automated Battery. RESULTS: TBR did not differ between
groups; however, TBR was positively correlated with inattentive symptoms in
AD/HD. Other correlations were found between EEG activity and neuropsychological
functions including spatial planning and decision making in the AD/HD group.
CONCLUSION: The results do not support the diagnostic value of TBR. Instead,
given the heterogeneous features, the results support the prognostic value of EEG
in AD/HD.
PMID- 28689464
TI - Predictive value of scintigraphic (semi-)quantitative thyroid parameters on
radioiodine therapy outcome in hyperthyroid cats.
AB - Objectives The outcome of radioiodine therapy in hyperthyroid cats is suspected
to be influenced by multiple factors. The degree of activity of the thyroid
gland, represented by uptake of sodium pertechnetate or tracer activities of
radioiodine by the thyroid gland on thyroid scintigraphy, has been suggested in
the literature as one of those. Thyroid gland pertechnetate uptake can be
represented by (semi-)quantitative factors such as the thyroid to salivary gland
(T/S) ratio, the thyroid to background (T/B) ratio and the percentage technetium
uptake by the thyroid glands (%TcU). The aim of this study was to investigate a
possible relationship between these thyroid scan parameters and radioiodine
therapy outcome. Methods Sodium pertechnetate thyroid scans of 75 hyperthyroid
cats were retrospectively evaluated and statistical analysis was performed with
and without correction for injected radioiodine activity. Three different
background regions of interest (ROIs) were used to calculate the T/B ratio and
%TcU: 'neck', 'circle' and 'copy ROI'. Results Higher T/S ratios were found to be
significantly related to a persistent hyperthyroid outcome in both analyses. For
the T/S ratio, a threshold value of 5.4 was determined, with a sensitivity of 73%
and a specificity of 59%. An increased risk for persistent hyperthyroidism
compared with a final euthyroid outcome with an increased T/Bcircle ratio was
only found to be significant without correction for the activity of radioiodine
administered. For the %TcU no statistical significance was reached. Regarding a
low total thyroxine outcome, no significant relationships with any of the
investigated parameters were found. Conclusions and relevance The findings of
this study suggest that semi-quantification of thyroid gland uptake is best
performed using the T/S ratio. A T/S ratio ?5.4 is a possible indicator for an
increased risk of persistent hyperthyroidism.
PMID- 28689465
TI - Design, synthesis, and taste evaluation of a high-intensity umami-imparting
oxazole-based compound.
AB - Umami taste is imparted predominantly by monosodium glutamate (MSG) and 5'
ribonucleotides. Recently, several different classes of hydrophobic umami
imparting compounds, the structures of which are quite different from MSG, have
been reported. To obtain a novel umami-imparting compound, N-cinnamoyl
phenethylamine was chosen as the lead compound, and a rational structure
optimization study was conducted on the basis of the pharmacophore model of
previously reported compounds. The extremely potent umami-imparting compound 2
[[[2-[(1E)-2-(1,3-benzodioxol-5-yl)ethenyl]-4-oxazolyle]methoxy]methyl]pyridine,
which exhibits 27,000 times the umami taste of MSG, was found. Its terminal
pyridine residue and linear structure are suggested to be responsible for its
strong activity. The time taken to reach maximum taste intensity exhibited by it,
as determined by the time-intensity method, is 22.0 s, whereas the maximum taste
intensity of MSG occurs immediately. This distinct difference in the time-course
taste profile may be due to the hydrophobicity and strong receptor affinity of
the new compound.
PMID- 28689466
TI - Early Diagnosis and Treatment of Lennox-Gastaut Syndrome.
AB - Lennox-Gastaut syndrome (LGS) is a severe form of childhood-onset epilepsy
associated with high morbidity and mortality. The peak period for manifestations
of Lennox-Gastaut syndrome is between ages 3 and 5 years, a time of critical
brain development and corresponding vulnerability to the electroclinical
dysfunction arising from Lennox-Gastaut syndrome. Diagnosis is based on a triad
of symptoms: multiple seizure types, cognitive impairment, and slow spike-and
wave pattern on electroencephalography. In practice, Lennox-Gastaut syndrome
presentation is diverse, and there may be a delay between initial symptoms and
emergence of the full triad of clinical features. Additionally, differential
diagnosis is complicated by the resemblance of Lennox-Gastaut syndrome to other
forms of epilepsy and by the need for varied diagnostic techniques requiring
specific clinical skills. Because diagnosis is complex and early intervention may
lead to improved outcomes, clinicians should consider treatment when Lennox
Gastaut syndrome symptoms are present, even in the absence of a formal diagnosis.
PMID- 28689467
TI - An investigation into four different sit-stand workstation use schedules.
AB - Twelve office workers participated in a study investigating effects of four
sit/stand schedules (90-min sit/30-min stand, 80/40, 105/15, and 60/60) via
several objective and subjective measures (muscle fatigue, foot swelling, spinal
shrinkage, and self-reported discomfort). Results showed that there were no
significant differences in shoulder and low back static muscle activities between
sitting and standing. Muscle fatigue was developed during workday under all
schedules. The longest standing schedule seemed to have a tendency of reducing
muscle fatigue. None of the schedules helped or worsened foot swelling and spinal
shrinkage. More active break-time activities seemed reducing muscle fatigue and
foot swelling. While the self-reported bodily discomfort levels were generally
low, the preferred schedules among the participants were varied, although the
least standing schedule was the least preferred. We may conclude that effects of
using sit-stand workstation to improve musculoskeletal health may be limited but
promoting more active break-time activities can help. Practitioner Summary: Sit
stand workstations are used to reduce work-related musculoskeletal disorders.
This study shows that office workers prefer sit/stand durations in the range
between 1:1 and 3:1. Longer standing may have the potential to reduce muscle
fatigue. However, active break-time activities may be more effective in reducing
muscle fatigue and foot swelling.
PMID- 28689468
TI - A discussion of nursing students' experiences of culture shock during an
international clinical placement and the clinical facilitators' role.
AB - AIM: This paper examines the meaning and experience of culture shock for nursing
students undertaking an international clinical placement (ICP) and the role of
the clinical facilitator. RESULTS: Oberg's four stages of adapting to culture
shock were aligned to anecdotal conversations with nursing students on an ICP.
All four stages were identified in anecdotal conversations with the students.
Support by the accompanying clinical facilitator is pivotalin overcoming culture
shock and maximising the learning experience. CONCLUSION: It is essential that
students are prepared for the change in cultural norms and are supported by the
academic staff to work through the processes required to adapt to culture shock.
Planning and preparation prior to departure is essential to assist with managing
culture shock with an emphasis on the inclusion of cultural norms and beliefs.
The role of the facilitator is crucial to guide and support the students through
the culture shock process.
PMID- 28689469
TI - A Mindfulness Program Manual for People With Dementia.
AB - This article describes a 10-session group-based Mindfulness Program for people
with mild to moderate dementia. It aims to equip people with dementia with skills
to manage psychological distress, with support from carers. The Mindfulness
Program was developed through reviews of existing literature, consultation with
experts, and a focus group with people with dementia. In a randomized controlled
feasibility and pilot trial with people with mild to moderate dementia in care
homes, it was found to significantly increase quality of life. The manual
presented here is designed to be administered flexibly to promote participants'
personhood. The protocol is designed for use by therapists with experience in
practicing mindfulness meditation.
PMID- 28689470
TI - Analysis and comparison of wrist splint designs using the finite element method:
Multi-material three-dimensional printing compared to typical existing practice
with thermoplastics.
AB - Rheumatoid arthritis is a chronic disease affecting the joints. Treatment can
include immobilisation of the affected joint with a custom-fitting splint, which
is typically fabricated by hand from low temperature thermoplastic, but the
approach poses several limitations. This study focused on the evaluation, by
finite element analysis, of additive manufacturing techniques for wrist splints
in order to improve upon the typical splinting approach. An additive
manufactured/3D printed splint, specifically designed to be built using Objet
Connex multi-material technology and a virtual model of a typical splint,
digitised from a real patient-specific splint using three-dimensional scanning,
were modelled in computer-aided design software. Forty finite element analysis
simulations were performed in flexion-extension and radial-ulnar wrist movements
to compare the displacements and the stresses. Simulations have shown that for
low severity loads, the additive manufacturing splint has 25%, 76% and 27% less
displacement in the main loading direction than the typical splint in flexion,
extension and radial, respectively, while ulnar values were 75% lower in the
traditional splint. For higher severity loads, the flexion and extension
movements resulted in deflections that were 24% and 60%, respectively, lower in
the additive manufacturing splint. However, for higher severity loading, the
radial defection values were very similar in both splints and ulnar movement
deflection was higher in the additive manufacturing splint. A physical prototype
of the additive manufacturing splint was also manufactured and was tested under
normal conditions to validate the finite element analysis data. Results from
static tests showed maximum displacements of 3.46, 0.97, 3.53 and 2.51 mm
flexion, extension, radial and ulnar directions, respectively. According to these
results, the present research argues that from a technical point of view, the
additive manufacturing splint design stands at the same or even better level of
performance in displacements and stress values in comparison to the typical low
temperature thermoplastic approach and is therefore a feasible approach to splint
design and manufacture.
PMID- 28689471
TI - The SCOPE-PC instrument for assessing patient safety culture in primary care: a
psychometric evaluation.
AB - INTRODUCTION: Primary healthcare differs from hospitals in terms of - inter alia
organisational structure. Therefore, patient safety culture could differ between
these settings. Various instruments have been developed to measure collective
attitudes of personnel within a primary healthcare organisation. However, the
number of valid and reliable instruments is limited. OBJECTIVES: Psychometric
properties of the SCOPE-Primary Care instrument were tested to examine the
instrument's applicability in home care services in Belgium. METHODS: A cross
sectional study was conducted by administering the SCOPE-PC questionnaire in a
single home care organisation with more than 1000 employees, including nurses,
midwives, healthcare assistants, diabetes educators and nursing supervisors.
First, a confirmatory factor analysis was performed to test whether the observed
dataset fitted to the proposed seven-factor model of the SCOPE-PC instrument.
Second, Cronbach's alphas were calculated to examine internal consistency
reliability. Finally, the instrument's validity was also examined. RESULTS: In
total, 603 questionnaires were retained for further analysis, representing an
overall response rate of 43.9%. Most respondents were nursing staff, followed by
healthcare assistants and nursing supervisors. The results of the confirmatory
factor analyses satisfied the chosen cut-offs, indicating an acceptable to good
model fit. With the exception of the dimension 'organizational learning' (0.58),
Cronbach's alpha scores of the SCOPE-PC scales indicated a good level of internal
consistency: 'open communication and learning from error' (0.86), 'handover and
teamwork' (0.78), 'adequate procedures and working conditions' (0.73), 'patient
safety management' (0.81), 'support and fellowship' (0.75), and 'intention to
report events (0.85). Moreover, inter-correlations between the seven dimensions
as well as with the patient safety grade were moderate to good. CONCLUSIONS: The
present study indicated that the SCOPE-Primary Care instrument has good
psychometric properties for home care services in Belgium. No modifications are
required to the original questionnaire in order to allow benchmarking between
primary healthcare settings.
PMID- 28689472
TI - Politics and Professions: Interdisciplinary Team Models and Their Implications
for Health Equity in Ontario.
AB - Ontario's efforts to reform primary care through interdisciplinary primary care
teams are unprecedented in Canada. Since 2004, the provincial government has
focused its reform efforts on three models: Family Health Teams (FHTs), Community
Health Centres (CHCs), and Nurse Practitioner-led Clinics (NPLCs). These models
vary by team structure, funding, and governance. I examine the strong preference
for the FHT model by the government and medical profession, and the implications
of this preference on health equity. The opportunity for teams to increase health
equity in Ontario may be limited due to the preference for physician-centered
FHTs over more egalitarian team models.
PMID- 28689473
TI - Psychiatric Comorbidities Modify the Association Between Childhood ADHD and Risk
for Suicidality: A Population-Based Longitudinal Study.
AB - OBJECTIVE: The objective of this study was to evaluate the effect of psychiatric
comorbidities on the association between childhood ADHD and suicidality among
adults. METHOD: Subjects were recruited from a population-based birth cohort.
Participating adult subjects with childhood ADHD and non-ADHD controls were
administered a structured psychiatric interview to assess suicidality and
psychiatric comorbidities. Associations were assessed using logistic regression.
RESULTS: Compared with controls, ADHD cases were significantly more likely to
meet criteria for suicidality. Subjects with childhood ADHD who met criteria for
generalized anxiety disorder had a higher than expected risk of suicidality with
an observed odds ratio of 10.94 (95% confidence interval [4.97, 24.08]) compared
with an expected odds ratio of 4.86, consistent with a synergistic interaction
effect. Significant synergistic interactions were also observed for hypomanic
episode and substance-related disorders. CONCLUSION: Childhood ADHD is
significantly associated with adult suicidal risk. Comorbidity between ADHD and
some psychiatric disorders is associated with a higher suicidal risk than
expected.
PMID- 28689474
TI - A qualitative phenomenological analysis of the subjective experience and
understanding of the at risk mental state.
AB - Over recent years there has been a growing interest in identifying the early
stages of psychosis. The At Risk Mental State (ARMS) is characteristic of the
prodromal stages of psychosis and its identification gives rise to a number of
clinical and research opportunities including early intervention and prevention
of psychosis. This study employs interpretative phenomenological analysis to gain
insights into the subjective experience and individuals understanding of the
development of their ARMS. Five participants took part and provided information
on the experience of symptoms, life prior to onset of their ARMS and their
understanding of symptoms and their development through a semi structured
interview. From the analysis of transcripts eight themes emerged which were
common across participants accounts. Three themes of experience (disturbed
world/disturbed self, disconnection with the world, thunderstruck) and five
themes of understanding (absence of understanding, use of others, identity,
forming links, fragmented understanding) were identified. Themes are explored in
detail and discussed in relation to existing literature and theory. Clinical
implications, directions for future research, and limitations are discussed
within.
PMID- 28689475
TI - Comparisons between Shikoro-type helmet with no hood and typical fire protective
helmets with hood in a hot and humid environment.
AB - The purpose of this study was to evaluate physiological and subjective responses
while wearing the Shikoro-type helmet for firefighters when compared to typical
helmets. Eight firefighters conducted a 30-min exercise at a 5 km h-1 in three
helmet conditions at an air temperature of 32 degrees C with 70%RH. The results
showed that no significant differences in rectal, mean skin temperature and
physiological strain index among the three conditions were found during exercise
and recovery. Skin temperatures on the cheek, ear and neck during exercise were
significantly lower for the Shikoro-type condition (p < 0.05), but forehead
temperature was greater for the Shikoro-type helmet when compared to the other
conditions (p < 0.05). Statistical differences in thermal sensation and thermal
comfort for overall and local body regions were not found among the three
conditions. These results imply that the Shikoro-type helmet had local advantages
in reducing skin temperatures on the face and neck. Practitioner Summary:
Firefighters wear their helmet with its hood to protect the head and neck but a
Shikoro type helmet has no fire protective hood. This study aimed to evaluate the
comfort function of Shikoro helmet along with typical helmets. The results
demonstrated thermal benefits of the Shikoro helmet on the head.
PMID- 28689476
TI - The role of music therapy in rehabilitation: improving aphasia and beyond.
AB - Music is part of the human nature, and it is also philogenically relevant to
language evolution. Language and music are bound together in the enhancement of
important social functions, such as communication, cooperation and social
cohesion. In the last few years, there has been growing evidence that music and
music therapy may improve communication skills (but not only) in different
neurological disorders. One of the plausible reasons concerning the rational use
of sound and music in neurorehabilitation is the possibility to stimulate brain
areas involved in emotional processing and motor control, such as the fronto
parietal network. In this narrative review, we are going to describe the role of
music therapy in improving aphasia and other neurological disorders, underlying
the reasons why this tool could be effective in rehabilitative settings,
especially in individuals affected by stroke.
PMID- 28689477
TI - Impact of biological activated carbon pre-treatment on the hydrophilic fraction
of effluent organic matter for mitigating fouling in microfiltration.
AB - The hydrophilic (HPI) fraction of effluent organic matter, which has protein and
carbohydrate contents, has a high propensity to foul low-pressure membranes.
Biological activated carbon (BAC) filtration was examined as a pre-treatment for
reducing the fouling of a microfiltration (MF) membrane (0.1 um PVDF) by the HPI
organic fraction extracted from a biologically treated secondary effluent (BTSE).
Although the BAC removed less dissolved organic carbon, carbohydrate and protein
from the HPI fraction than the granular activated carbon treatment which was used
for comparison, it led to better improvement in permeate flux. This was shown to
be due to the removal/breakdown of the HPI fraction resulting in less deposition
of these organics on the membrane, many components of which are high molecular
weight biopolymers (such as protein and carbohydrate molecules) through
biodegradation and adsorption of those molecules on the biofilm and activated
carbon. This study established the potential of BAC pre-treatment for reducing
the HPI fouling of the membrane and thus improving the performance for the MF of
BTSE for water reclamation.
PMID- 28689478
TI - Beyond a Western Bioethics in Asia and Its Implication on Autonomy.
AB - Despite flourishing as a multidisciplinary subject, the predominant view in
bioethics today is based on Anglo-American thought. This has serious implications
for a global bioethics that needs to be contextualized to local cultures and
circumstances in order to be relevant. Being the largest continent on the earth,
Asia is home to a variety of cultures, religions and countries of different
economic statuses. While the practice of medicine in the East and West may be
similar, its ethical practices do differ. Thus, the Western understanding of
autonomy may not be wholly applicable in the Asian setting, especially in the
setting of breaking bad news, giving consent, determining best interests and
deciding on end-of-life care. This article explores these topics in depth,
attempting to find shared integrating factors, but at the same time arguing for a
modified ethical application of autonomy, based on Asian beliefs.
PMID- 28689479
TI - Introduction to the 25th anniversary AmBisome(r) Festschrift.
PMID- 28689481
TI - Histological Evaluation of a Self-Expanding Stent-Graft 23 Months After
Implantation in the Superficial Femoral Artery.
AB - PURPOSE: To report histological examination of a Viabahn stent-graft implanted in
the superficial femoral artery (SFA) for nearly 2 years. CASE REPORT: A 78-year
old man with peripheral artery disease was treated successfully with a 6.0*250-mm
Viabahn self-expanding stent-graft in the right SFA, relieving his lower limb
claudication. The patient died suddenly due to acute myocardial infarction 23
months later. Histological evaluation of the stent-graft implantation site
revealed moderate neointimal proliferation at both proximal and distal edges of
the device. In the middle part of the stent, significant macrophages and
multinucleated foreign body giant cells had accumulated, although the stent was
entirely patent. Furthermore, no endothelial cell coverage was found. CONCLUSION:
Judging from these features, it might be necessary to continue dual antiplatelet
therapy after stent-graft implantation over the long term to prevent thrombosis
and subsequent restenosis or reocclusion.
PMID- 28689480
TI - Prevalence and risk factors of brucellosis among veterinary health care
professionals.
AB - The study describes prevalence, clinical symptoms and risk factors for
brucellosis in personnel engaged in veterinary health care in Karnataka, India. A
total of 1050 sera samples were collected from animal handlers, veterinarians,
veterinary students, para-veterinarians and persons engaged in artificial
insemination of animals. The sera samples were tested for brucellosis by Rose
Bengal plate test (RBPT), serum agglutination test (SAT), IgG and IgM indirect
ELISA and PCR. Age, sex, clinical symptoms and risk factors were recorded in
structured questionnaire. Of the 1050 samples tested, 6.76, 6.38, 3.90, 2.67 and
2.0% were positive by IgG ELISA, RBPT, SAT, IgM ELISA and PCR, respectively and
overall prevalence recorded was 7.04%. The prominent clinical symptoms observed
were intermittent fever (71.62%) followed by joint pain and body aches. A high
degree of suspicion, awareness and multimodal diagnostic approach is suggested
for early diagnosis, treatment and disease follow up.
PMID- 28689482
TI - A Semiautomated Method for Measuring the 3-Dimensional Fabric to Renal Artery
Distances to Determine Endograft Position After Endovascular Aneurysm Repair.
AB - PURPOSE: To report a methodology for 3-dimensional (3D) assessment of the stent
graft deployment accuracy after endovascular aneurysm repair (EVAR). METHODS: A
methodology was developed and validated to calculate the 3D distances between the
endograft fabric and the renal arteries over the curve of the aorta. The shortest
distance between one of the renal arteries and the fabric (SFD) and the distance
from the contralateral renal artery to the fabric (CFD) were determined on the
first postoperative computed tomography (CT) scan of 81 elective EVAR patients.
The SFDs were subdivided into a target position (0-3 mm distal to the renal
artery), high position (partially covering the renal artery), and low position
(>3 mm distal to the renal artery). Data are reported as the median
(interquartile range, IQR). RESULTS: Intra- and interobserver agreements for
automatic and manual calculation of the SFD and CFD were excellent (ICC >0.892,
p<0.001). The median SFD was 1.4 mm (IQR -0.9, 3.0) and the median CFD was 8.0 mm
(IQR 3.9, 14.2). The target position was achieved in 44%, high position in 30%,
and low position in 26% of the patients. The median slope of the endograft toward
the higher renal artery was 2.5 degrees (IQR -5.5 degrees , 13.9 degrees ).
CONCLUSION: The novel methodology using 3D CT reconstructions enables accurate
evaluation of endograft position and slope within the proximal aortic neck. In
this series, only 44% of endografts were placed within the target position with
regard to the lowermost renal artery.
PMID- 28689483
TI - The Influence of Positioning of the Nellix Endovascular Aneurysm Sealing System
on Suprarenal and Renal Flow: An In Vitro Study.
AB - PURPOSE: To examine the influence of device positioning and infrarenal neck
diameter on flow patterns in the Nellix endovascular aneurysm sealing (EVAS)
system. METHODS: The transition of the aortic flow lumen into two 10-mm-diameter
stents after EVAS creates a mismatched area. Flow recirculation may affect local
wall shear stress (WSS) profiles and residence time associated with
atherosclerosis and thrombosis. To examine these issues, 7 abdominal aortic
aneurysm flow phantoms were created, including 3 unstented controls and 3 stented
models with infrarenal neck diameters of 24, 28, and 32 mm. Stents were
positioned within the instructions for use (IFU). Another 28-mm model was created
to evaluate lower positioning of the stents outside the IFU (28-mm LP). Flow was
visualized using optical particle imaging velocimetry (PIV) and quantified by
time-averaged WSS (TAWSS), oscillatory shear index (OSI), and relative residence
time (RRT) in the aorta at the anteroposterior (AP) midplane, lateral midplane,
and renal artery AP midplane levels. RESULTS: Flow in the aorta AP midplane was
similar in all models. Vortices were observed in the stented models in the
lateral midplane near the anterior and posterior walls. In the 32-mm IFU and 28
mm LP models, a steady state of vortices appeared, with varying location during a
cycle. In all models, a low TAWSS (<10-2 Pa) was observed at the anterior wall of
the aorta with peak OSI of 0.5 and peak RRT of 104 Pa-1. This region was more
proximally located in the stented models. The 24- and 28-mm IFU models showed
flow with a higher velocity at the renal artery inflow compared to controls.
TAWSS in the renal artery was lower near the orifice in all models, with the
largest area in the 24-mm IFU model. OSI and RRT in the renal artery were near
zero for all models. CONCLUSION: EVAS enhances vorticity proximal to the seal
zone, especially with lower positioning of the device and in larger neck
diameters. Endobags just below the renal artery affect the flow profile in a
minor area of this artery in 24- and 28-mm necks, while lower stent positioning
does not influence the renal artery flow profile.
PMID- 28689484
TI - Transcatheter Aortic Valve Implantation as a Bailout Procedure for Acute Aortic
Valve Regurgitation During Endovascular Arch Repair.
AB - PURPOSE: To report emergent transcatheter aortic valve implantation (TAVI) to
treat acute severe aortic regurgitation caused by valve cusp dysfunction
following proximal migration of an endograft implanted in the ascending aorta
during endovascular arch repair. CASE REPORT: A 65-year-old man had been
previously treated with thoracic and fenestrated endografts in a 2-stage
procedure for a chronic type B dissection. At 2-year follow-up, aneurysmal
evolution of the distal arch led to development of a proximal type Ia endoleak.
The patient was deemed unfit for open repair because of severe
nonrevascularizable coronary artery disease. A custom-made endograft was designed
consisting of a double inner branch arch endograft with a proximal component to
reline the ascending aorta to avoid iatrogenic type A dissection. The first
component was successfully deployed. However, this device migrated toward the
aortic valve when the delivery system of the branch device was advanced through
the aortic valve. Aortography and transesophageal echography showed acute aortic
regurgitation due to obstruction of the left coronary valve cusp. An emergency
bailout TAVI procedure was performed to successfully treat the aortic
regurgitation. CONCLUSION: TAVI can be used as a bailout procedure for acute
aortic valve dysfunction during endovascular arch or ascending aorta repair.
PMID- 28689485
TI - Therapeutic ultrasound after sciatic nerve compression of Wistar rats.
AB - OBJECTIVES: The present study analyzed the effect of therapy with therapeutic
ultrasound on the sciatic nerve after compression injury, comparing two similar
doses of SATA. METHODS: In total, 32 Wistar rats were used, divided into the
following groups: CG - control; IG - compression injury of the sciatic nerve;
IGCU - injury and continuous ultrasound; and IGPU - injury and 20% pulsed
ultrasound. The treatment with ultrasound started on the 3rd postoperative day,
with a frequency of 1 MHz, 0.4 W/cm2 (SATA) for IGCU. IGPU received 2.0 W/cm2
(SATP), with 20% of the active cycle, for 3 minutes. The treatment was performed
on a daily basis, totaling 15 days of therapy. Evaluations were performed for
functional, histological, and morphometric forms. RESULTS: Both the Sciatic
Functional Index and the withdrawal threshold and grip strength failed to show an
advantage of using therapeutic ultrasound. For the morphometric evaluations of
nerve fiber diameter and axons, myelin sheath thickness, and G quotient and nerve
fiber estimates, IGPU values were estimated to be significantly lower. The
morphological analysis revealed intense inflammatory response and
neovascularization, as well as degeneration of axons and the myelin sheath, for
the injury group and IGCU; however, IGPU showed greater tissue disorganization.
CONCLUSION: There were no significant differences, showing functional or
nocicepitive recovery of the treated groups, including with characteristics
pointing to the pulsed group with worse results.
PMID- 28689486
TI - Superiority of Roeder's Knot for Fascial Mesh Fixation in a Cadaveric Model.
AB - OBJECTIVE: This study compares the use of Roeder's knot (1:3:1, 1 hitch, 3 winds,
and 1 locking hitch) to the surgeon's knot regarding the security of the knot and
predictability of its position. METHOD: A polypropylene mesh was secured to the
undersurface of the abdominal wall of a fresh frozen cadaver using tacks. Eight
standardized transfascial sutures were performed. Four of them were secured with
surgeon's knot and the remaining 4 were tied with Roeder's knot. A Mosquito
hemostat was placed between the mesh and the stitch loop and the distance between
its jaws was measured. We then created subcutaneous flap and measured the
vertical distance between the knot and the anterior sheath. RESULTS: When
surgeon's knot was used, the distance between the mesh and the stitch loop ranged
between 4 and 6 mm. This distance could not be measured when Roeder's knot was
used due to inability to place hemostat between the mesh and the stitch loop. The
vertical length between the anterior sheath and the surgeon knot ranged between 3
and 13 mm while remaining consistent at 2 mm when Roeder's knot was applied.
CONCLUSIONS: This study shows that Roeder's knot is superior to the regular
sliding knot in securing the mesh to the abdominal wall. It can be tightened
appropriately and leads to less variation when used properly. It has many other
applications that stem from its ability to be advanced with different degrees of
tightness based on body habitus and the operative requirements.
PMID- 28689487
TI - The ALPPS in the Treatment of Hepatitis B-Related Hepatocellular Carcinoma With
Cirrhosis: A Single-Center Study and Literature Review.
AB - BACKGROUND: Associating liver partition and portal vein ligation for staged
hepatectomy (ALPPS) has been reported to be a new treatment strategy for patients
with predicted small volumes of future liver remnant (FLR). ALPPS is associated
with rapid hypertrophy of FLR but it has a high postoperative mortality and
morbidity. Up to now, it is controversial to apply ALPPS in hepatocellular
carcinoma, especially for patients with liver cirrhosis. METHODS: Between May
2014 and June 2015, consecutive patients who underwent ALPPS with hepatitis B
related hepatocellular carcinoma with cirrhosis carried out in our center were
included into the study. Demographic characteristics, surgical outcomes, and
pathological results were evaluated. Subsequently, follow-up was still in
progress. RESULTS: The median operating time of the first (n = 12) and the second
procedures (n = 10) were 285.0 and 212.5 minutes, respectively. The median blood
loss were 200 and 800 mL for 2 stages of operations. The severe complication
(>=IIIB) rates for the first and the second operations were 25.0% versus 40.0%,
respectively. Six patients with too small future live remnant died of
postoperative hepatic failure. On a median follow-up of 16 months of the 6
patients discharged, 4 patients were still alive and of 2 were disease-free.
CONCLUSION: In terms of the feasibility and safety, this study showed that ALPPS
in the treatment of hepatocellular carcinoma with insufficient future liver
remnant might be a double-edged sword, and careful patients selected was
proposed. Too small of FLR/SLV, less than 30%, is not recommended for ALPPS in
liver with cirrhosis.
PMID- 28689488
TI - Modified Laparoscopic Pyloroplasty During Laparoscopic Splenectomy and
Azygoportal Disconnection for the Prevention of Postoperative Gastroparesis.
AB - BACKGROUND: Gastroparesis is a common complication after splenectomy and
azygoportal disconnection, remaining a chronic debilitating disorder with
considerable treatment challenges. To minimize postoperative gastroparesis, we
have developed a new modified laparoscopic pyloroplasty (LP) technique for use
during laparoscopic splenectomy and azygoportal disconnection (LSD). METHODS: We
retrospectively evaluated the outcomes of 31 cirrhotic patients with portal
hypertensive bleeding and secondary hypersplenism who underwent synchronous LSD
with modified LP (n = 14) or LSD without modified LP (n = 17) between January
2015 and August 2015. Perioperative variables were compared. RESULTS: LSD with
and without modified LP were successful in all patients. Operation time was
significantly longer for LSD with modified LP than LSD without modified LP ( P =
.001). However, the LSD with modified LP group had significantly reduced
incidences of bloating 1 month postoperatively ( P < .05), nausea ( P < .05), and
bloating ( P < .05) 3 months postoperatively, gastric retention 3 months
postoperatively ( P < .0001), and prokinetic use at 1 month ( P = .009) and 3
months postoperatively ( P < .05) compared with the LSD without modified LP
group. Gastric emptying scintigraphy showed that the mean time required to empty
50% of the ingested meal was significantly shorter in the LSD with modified LP
group than in the LSD without modified LP group at 3 months postoperatively (74.3
+/- 19.1 vs 261.7 +/- 61.0 minutes, P < .0001). CONCLUSIONS: Modified LP during
LSD was feasible, effective, and safe, and significantly reduced short-term
symptoms of postoperative gastroparesis.
PMID- 28689489
TI - Correlation between serum ferritin and bone marrow iron stores.
AB - Bone marrow aspirate examination is a gold standard to assess bone marrow iron
stores. The correlation between serum ferritin and bone marrow iron has not been
established in detail, as the cutoff value for iron stores have not been
uniformly established. Ours was a cross-sectional study. Perl's Prussian blue
stain was used to stain bone marrow, assessed by Gale's grading. Receiver
operating characteristic curve analysis and Spearman's correlation coefficient
calculated. Gale's grading revealed iron store deficiency in 26 and sufficiency
in 13. Spearman's correlation coefficient of 0.90 showed a significant relation
between serum ferritin and bone marrow iron stores. A serum ferritin of 228
pmol/L had high sensitivity and specificity for iron deficiency; our study
suggests that this level be taken as the cutoff value to predict iron store
deficiency in bone marrow.
PMID- 28689491
TI - Deceptive nasal NK/T-cell lymphoma.
AB - Nasal NK/T cell lymphoma is rare and it easily masquerades as chronic
rhinosinusitis. It has a very poor prognosis and hence early diagnosis, although
difficult, is necessary for better outcome. We present a case of a 30-year-old
man who presented with nasal obstruction, facial oedema and crusts. High
resolution computed tomography found soft tissue in all sinuses and the nasal
cavity. Endoscopic biopsy revealed necrotic and inflammatory tissue with fungi on
culture. A diagnosis of fungal rhinosinusitis was made but the patient did not
respond to antifungal drugs. A histopathology review with immunohistochemistry
suggested nasal NK/T cell lymphoma. The patient was started on chemotherapy but
died within 1 week.
PMID- 28689492
TI - Autoimmune haemolytic anaemia and haemophagocytic lymphohistiocytosis in an
adolescent boy with tuberculosis: an unusual association.
PMID- 28689494
TI - Editorial: Circadian Rhythms are Everywhere: Except in Neurodegenerative
Disorders.
PMID- 28689493
TI - HIV-associated executive dysfunction in the era of modern antiretroviral therapy:
A systematic review and meta-analysis.
AB - OBJECTIVE: While some reports suggest that HIV+ individuals continue to display
executive function (EF) impairment in the era of cART, findings have been
contradictory and appear to differ based on the aspect of EF being measured. To
improve the understanding of how discrete executive abilities may be
differentially affected or spared in the context of HIV infection, we conducted a
systematic review and meta-analysis to (a) determine whether and to what extent
HIV+ adults experience deficits in EFs, and (b) understand how demographic and
clinical characteristics may modify the associations between HIV infection and
executive abilities. METHOD: Studies comparing HIV+ and HIV-uninfected groups on
measures of working memory, set-shifting, inhibition, decision-making, and apathy
between 2000 and 2017 were identified from three databases. Effect sizes (Cohen's
d) were calculated using inverse variance weighted random effects models. Meta
regression was used to examine the moderating effect of demographic and clinical
variables. RESULTS: Thirty-seven studies (n = 3935 HIV+; n = 2483 HIV-uninfected)
were included in the meta-analysis. Pooled effect sizes for deficits associated
with HIV infection were small for domains of set-shifting (d = -0.34, 95% CI [
0.47, -0.20]) and inhibition (d = -0.31, 95% CI [-0.40, -0.21]), somewhat larger
for measures of decision-making (d = -0.41, 95% CI [-0.53, -0.28]) and working
memory (d = -0.42, 95% CI [-0.59, -0.29]), and largest for apathy (d = -0.87, 95%
CI [-1.09, -0.66]). Meta-regression demonstrated that age, sex, education,
current CD4 count, and substance dependence differentially moderated the effects
of HIV infection on specific EFs. However, lower nadir CD4 count was the only
variable associated with greater deficits in nearly all EF domains. CONCLUSIONS:
Our results suggest that discrete domains of EF may be differentially affected by
HIV infection and moderating demographic and clinical variables. These findings
have implications for the development of targeted cognitive remediation
strategies.
PMID- 28689495
TI - Machine learning methods to predict child posttraumatic stress: a proof of
concept study.
AB - BACKGROUND: The care of traumatized children would benefit significantly from
accurate predictive models for Posttraumatic Stress Disorder (PTSD), using
information available around the time of trauma. Machine Learning (ML)
computational methods have yielded strong results in recent applications across
many diseases and data types, yet they have not been previously applied to
childhood PTSD. Since these methods have not been applied to this complex and
debilitating disorder, there is a great deal that remains to be learned about
their application. The first step is to prove the concept: Can ML methods - as
applied in other fields - produce predictive classification models for childhood
PTSD? Additionally, we seek to determine if specific variables can be identified
from the aforementioned predictive classification models - with putative causal
relations to PTSD. METHODS: ML predictive classification methods - with causal
discovery feature selection - were applied to a data set of 163 children
hospitalized with an injury and PTSD was determined three months after hospital
discharge. At the time of hospitalization, 105 risk factor variables were
collected spanning a range of biopsychosocial domains. RESULTS: Seven percent of
subjects had a high level of PTSD symptoms. A predictive classification model was
discovered with significant predictive accuracy. A predictive model constructed
based on subsets of potentially causally relevant features achieves similar
predictivity compared to the best predictive model constructed with all
variables. Causal Discovery feature selection methods identified 58 variables of
which 10 were identified as most stable. CONCLUSIONS: In this first proof-of
concept application of ML methods to predict childhood Posttraumatic Stress we
were able to determine both predictive classification models for childhood PTSD
and identify several causal variables. This set of techniques has great potential
for enhancing the methodological toolkit in the field and future studies should
seek to replicate, refine, and extend the results produced in this study.
PMID- 28689496
TI - Rapidly increasing end-of-life care needs: a timely warning.
AB - Current trends in population ageing show that, in the near future, while more
people will live longer, more will also die at any one time. Health systems, as
well as individual practitioners, are only just becoming aware of the extent of
this problem. Health systems will have to rapidly change practice to manage the
number of people dying in the coming years, many with complex multimorbid
conditions. The changes involved should include a personal recognition by all
health professionals of their role in caring for the dying, and healthcare
education must include end-of-life care management as part of the core
curriculum. Further, health systems must improve integration between primary care
and specialist clinicians to ensure the burden is shared efficiently across the
system. Finally, it should be recognised that end-of-life care is not terminal
care, but should be anticipated months or sometimes years ahead through advance
care planning for known future complications by the patient's clinical team, as
well as by patients and their main carers, to manage crises as they ariserather
than react to them once they arise.Please see related article:
https://bmcmedicine.biomedcentral.com/articles/ 10.1186/s12916-017-0860-2 .
PMID- 28689497
TI - Corporate political activity of the dairy industry in France: an analysis of
publicly available information.
AB - OBJECTIVE: In the present study, we used a structured approach based on publicly
available information to identify the corporate political activity (CPA)
strategies of three major actors in the dairy industry in France. DESIGN: We
collected publicly available information from the industry, government and other
sources over a 6-month period, from March to August 2015. Data collection and
analysis were informed by an existing framework for classifying the CPA of the
food industry. Setting/Subjects Our study included three major actors in the
dairy industry in France: Danone, Lactalis and the Centre National
Interprofessionnel de l'Economie Laitiere (CNIEL), a trade association. RESULTS:
During the period of data collection, the dairy industry employed CPA practices
on numerous occasions by using three strategies: the 'information and messaging',
the 'constituency building' and the 'policy substitution' strategies. The most
common practice was the shaping of evidence in ways that suited the industry. The
industry also sought involvement in the community, establishing relationships
with public health professionals, academics and the government. CONCLUSIONS: Our
study shows that the dairy industry used several CPA practices, even during
periods when there was no specific policy debate on the role of dairy products in
dietary guidelines. The information provided here could inform public health
advocates and policy makers and help them ensure that commercial interests of
industry do not impede public health policies and programmes.
PMID- 28689498
TI - The slow death of the concept of schizophrenia and the painful birth of the
psychosis spectrum.
AB - The concept of schizophrenia only covers the 30% poor outcome fraction of a much
broader multidimensional psychotic syndrome, yet paradoxically has become the
dominant prism through which everything 'psychotic' is observed, even affective
states with mild psychosis labelled 'ultra-high risk' (for schizophrenia). The
inability of psychiatry to frame psychosis as multidimensional syndromal
variation of largely unpredictable course and outcome - within and between
individuals - hampers research and recovery-oriented practice. 'Psychosis'
remains firmly associated with 'schizophrenia', as evidenced by a vigorous stream
of high-impact but non-replicable attempts to 'reverse-engineer' the hypothesized
biological disease entity, using case-control paradigms that cannot distinguish
between risk for illness onset and risk for poor outcome. In this paper, the main
issues surrounding the concept of schizophrenia are described. We tentatively
conclude that with the advent of broad spectrum phenotypes covering autism and
addiction in DSM5, the prospect for introducing a psychosis spectrum disorder -
and modernizing psychiatry - appears to be within reach.
PMID- 28689499
TI - Successful ageing, depression and resilience research; a call for a priori
approaches to investigations of resilience.
AB - Given the multitude of risk factors for depression in modern society and given
the negative consequences of depressive problems for successful ageing,
investigating resilience in relation to depression may help identifying entry
points for reducing the burden of morbidity. Research on resilience begins with
the realisation that individuals may demonstrate good physical or psychological
functioning despite being exposed to risk experiences that can have serious
negative impact on functioning. Interest in investigating resilience within
ageing research has been increasing. Among the approaches toward investigating
resilience are so-called a priori approaches, where criteria for inferring
resilience are established a priori. In this editorial, we highlight some of the
advantages of taking a priori approaches to the study of resilience and we touch
on the implications for a priori approaches for the topic of resilience and
depression. We argue that depression should take a prominent role in resilience
research, because depression is strongly associated with opportunities for
successful ageing.
PMID- 28689500
TI - Night-time activity forecast by season and weather in a longitudinal design -
natural light effects on three years' rest-activity cycles in nursing home
residents with dementia.
AB - : Backround: Night-time agitation is a frequent symptom of dementia. It often
causes nursing home admission and has been linked to circadian rhythm
disturbances. A positive influence of light interventions on night-time agitation
was shown in several studies. The aim of our study was to investigate whether
there is a long-term association between regional weather data (as indicator for
daylight availability) and 24-hour variations of motor activity. METHODS: Motor
activity of 20 elderly nursing home residents living with dementia was analyzed
using recordings of continuously worn wrist activity monitors over a three-year
period. The average recording duration was 479 +/- 206 days per participant (mean
+/- SD). Regional cloud amount and day length data from the local weather station
(latitude: 52 degrees 56'N) were included in the analysis to investigate their
effects on several activity variables. RESULTS: Nocturnal rest, here defined as
the five consecutive hours with the least motor activity during 24 hours (L5),
was the most predictable activity variable per participant. There was a
significant interaction of night-time activity with day length and cloud amount
(F 1,1174 = 4.39; p = 0.036). Night-time activity was higher on cloudy short days
than on clear short days (p = 0.007), and it was also higher on cloudy short days
than on cloudy long days (p = 0.032). CONCLUSIONS: The need for sufficient
zeitgeber (time cue) strength during winter time, especially when days are short
and skies are cloudy, is crucial for elderly people living with dementia.
Activity forecast by season and weather might be a valuable approach to
anticipate adequately complementary use of electrical light and thereby foster
lower night-time activity.
PMID- 28689501
TI - The association between educational parameters and a cognitive screening measure
in older blacks.
AB - : ABSTRACTBackground:To expand on prior literature by examining how various
education parameters (performance-based reading literacy, years of education, and
self-rated quality of education) relate to a cognitive screening measure's total
and subscale scores of specific cognitive abilities. METHODS: Black adults (age
range: 55-86) were administered self-rated items years of education and quality
of education, and a measure of performance-based reading literacy. The Mini
Mental State Examination (MMSE) was used to screen for overall cognitive
functioning as well as performance on specific cognitive abilities. RESULTS:
Sixty-nine percent of the sample had reading grade levels that were less than
their reported years of education. Lower years of education and worse reading
literacy are associated with poorer MMSE performance, particularly on the
attention and calculation subscales. CONCLUSIONS: Years of education, a commonly
used measure for education, may not be reflective of Black adults' educational
experiences/qualities. Thus, it is important to account for the unique
educational experiences of adults that could influence their MMSE performance.
Incorporating quality and quantity of education will provide a more comprehensive
understanding of the individual's performance on cognitive measures, specifically
as it relates to sociocultural differences.
PMID- 28689502
TI - Intrauterine growth restriction-induced deleterious adaptations in endothelial
progenitor cells: possible mechanism to impair endothelial function.
AB - Intrauterine growth restriction (IUGR) can induce deleterious changes in the
modulatory ability of the vascular endothelium, contributing to an increased risk
of developing cardiovascular diseases in the long term. However, the mechanisms
involved are not fully understood. Emerging evidence has suggested the potential
role of endothelial progenitor cells (EPCs) in vascular health and repair.
Therefore, we aimed to evaluate the effects of IUGR on vascular reactivity and
EPCs derived from the peripheral blood (PB) and bone marrow (BM) in vitro.
Pregnant Wistar rats were fed an ad libitum diet (control group) or 50% of the ad
libitum diet (restricted group) throughout gestation. We determined vascular
reactivity, nitric oxide (NO) concentration, and endothelial nitric oxide
synthase (eNOS) protein expression by evaluating the thoracic aorta of adult male
offspring from both groups (aged: 19-20 weeks). Moreover, the amount, functional
capacity, and senescence of EPCs were assessed in vitro. Our results indicated
that IUGR reduced vasodilation via acetylcholine in aorta rings, decreased NO
levels, and increased eNOS phosphorylation at Thr495. The amount of EPCs was
similar between both groups; however, IUGR decreased the functional capacity of
EPCs from the PB and BM. Furthermore, the senescence process was accelerated in
BM-derived EPCs from IUGR rats. In summary, our findings demonstrated the
deleterious changes in EPCs from IUGR rats, such as reduced EPC function and
accelerated senescence in vitro. These findings may contribute towards
elucidating the possible mechanisms involved in endothelial dysfunction induced
by fetal programming.
PMID- 28689503
TI - Long-term adaptation capacity of ponies: effect of season and feed restriction on
blood and physiological parameters.
AB - Domesticated horses are increasingly kept under semi-natural housing conditions,
whereas their adaptation capacity is not fully investigated. In all, 10 Shetland
pony mares were held under semi-extensive conditions for 1 year. In winter
animals were allocated into two feeding groups (60% and 100% of maintenance
energy requirement, respectively). Triiodothyronine, thyroxine, non-esterified
fatty acids (NEFA), total bilirubin, total protein, triglyceride, glucose,
insulin and hair length were measured at monthly intervals, whereas BW, body
condition score, cresty neck score and resting heart rate were recorded every 2
weeks. From summer to winter all Ponies showed a reduction in resting heart rate
(P0.05). Refeeding of restrictively fed ponies resulted in a rapid increase in
resting heart rate and BW and a return of blood parameters to reference values.
Adequately supplied animals adapted without difficulty to varying environmental
conditions, whereas feed restriction in ponies during winter resulted in reduced
resting heart rates suggesting a reduced basal metabolic rate. The energy
restriction was compensated by mobilizing body fat reserves which led to changes
in blood parameters. Refeeding in feed restricted animals revealed a remarkably
quick recovery of physiological and blood parameters to reference values. We
therefore suggest that year round-outdoor housing can be a suitable housing
system for robust horse breeds provided that an adequate food supply is
available.
PMID- 28689504
TI - A multinational and multidisciplinary approach to treat CHD in paediatric age in
Angola: initial experience of a medical-surgical centre for children with heart
disease in Angola.
AB - BACKGROUND: Epidemiological patterns of cardiac disease differ between developed
countries and African nations. Despite the collaborative efforts of developed
countries, several obstacles hinder the implementation of successful programmes
for the management of children with heart disease in Africa. Materials and
methods This study is a retrospective analysis of a bi-national two-institution
partnership programme for the treatment of children with congenital and acquired
heart disease. In April, 2011, a continuous medical-surgical programme was
inaugurated at Clinica Girassol in Luanda. The main goals were to initiate
permanent and local delivery of services while training local teams, allowing
autonomous medical and surgical management of children with heart disease.
RESULTS: Between April, 2011 and August, 2015, a total of 1766 procedures were
performed on 1682 children. Of them, 1539 had CHD and 143 had acquired heart
disease; 94 children underwent interventional treatment. A total of 1672
paediatric surgeries were performed on 1588 children: 1087 (65%) were performed
with extracorporeal circulation and 585 (35%) were off-pump. The age distribution
of the children was 4.5% (n=76) neonatal, 40.4% (n=675) between 30 days and 1
year, and 55.1% (n=921) over 1 year. There were 76 re-operations (4.5%) due to
complications. The 30-day mortality rate was 4.2% (71 patients). Education-wise,
several Angolan medical and surgical specialists were trained, allowing near
autonomous cardiac care delivery in children with heart disease. CONCLUSION: An
innovative cooperation model between a European and an African centre based on
permanent delivery of care and education allowed for effective training of local
teams and treatment of children with heart disease in their own environment.
PMID- 28689505
TI - Revision: review of non-elective hospitalisations of adults with CHD.
AB - : Introduction The adult CHD population is increasing and ageing and remains at
high risk for morbidity and mortality. In a retrospective single-centre study, we
conducted a comprehensive review of non-elective hospitalisations of adults with
CHD and explored factors associated with length of stay. METHODS: We identified
adults (?18 years) with CHD admitted during a 12-month period and managed by the
adult CHD service. Data regarding demographics, cardiac history, hospital
admission, resource utilisation, and length of stay were extracted. RESULTS:
There were 103 admissions of 91 patients (age 37+/-10 years; 52% female). Of 91
patients, 96% had moderate or complex defects. Of 103 admissions, 45% were
through the emergency department. The most common reasons for admission were
arrhythmia (37%) and heart failure (28%); 29% of admissions included a stay in
the ICU. The mean number of consultations by other services was 2.0.
Electrophysiology and anaesthesiology departments were most frequently consulted.
After removing outliers, the mean length of stay was 7.9+/-7.4 days (median=5
days). The length of stay was longer for patients admitted for heart failure
(12.2+/-10.3 days; p=0.001) and admitted directly to the ward (9.6+/-8.9 days;
p=0.009). CONCLUSIONS: Among non-electively hospitalised adults with CHD in a
tertiary-care centre, management often entails an interdisciplinary approach, and
the length of stay is longest for patients admitted with heart failure. The
healthcare system must ensure optimal resources to maintain high-quality care for
this expanding patient population.
PMID- 28689506
TI - Description and validation of a new automated surveillance system for Clostridium
difficile in Denmark.
AB - The surveillance of Clostridium difficile (CD) in Denmark consists of laboratory
based data from Departments of Clinical Microbiology (DCMs) sent to the National
Registry of Enteric Pathogens (NREP). We validated a new surveillance system for
CD based on the Danish Microbiology Database (MiBa). MiBa automatically collects
microbiological test results from all Danish DCMs. We built an algorithm to
identify positive test results for CD recorded in MiBa. A CD case was defined as
a person with a positive culture for CD or PCR detection of toxin A and/or B
and/or binary toxin. We compared CD cases identified through the MiBa-based
surveillance with those reported to NREP and locally in five DCMs representing
different Danish regions. During 2010-2014, NREP reported 13 896 CD cases, and
the MiBa-based surveillance 21 252 CD cases. There was a 99.9% concordance
between the local datasets and the MiBa-based surveillance. Surveillance based on
MiBa was superior to the current surveillance system, and the findings show that
the number of CD cases in Denmark hitherto has been under-reported. There were
only minor differences between local data and the MiBa-based surveillance,
showing the completeness and validity of CD data in MiBa. This nationwide
electronic system can greatly strengthen surveillance and research in various
applications.
PMID- 28689507
TI - A survey of zoonotic pathogens carried by house mouse and black rat populations
in Yucatan, Mexico.
AB - The house mouse (Mus musculus) and the black rat (Rattus rattus) are reservoir
hosts for zoonotic pathogens, several of which cause neglected tropical diseases
(NTDs). Studies of the prevalence of these NTD-causing zoonotic pathogens, in
house mice and black rats from tropical residential areas are scarce. Three
hundred and two house mice and 161 black rats were trapped in 2013 from two urban
neighbourhoods and a rural village in Yucatan, Mexico, and subsequently tested
for Trypanosoma cruzi, Hymenolepis diminuta and Leptospira interrogans. Using the
polymerase chain reaction we detected T. cruzi DNA in the hearts of 4.9% (8/165)
and 6.2% (7/113) of house mice and black rats, respectively. We applied the
sedimentation technique to detect eggs of H. diminuta in 0.5% (1/182) and 14.2%
(15/106) of house mice and black rats, respectively. Through the
immunofluorescent imprint method, L. interrogans was identified in 0.9% (1/106)
of rat kidney impressions. Our results suggest that the black rat could be an
important reservoir for T. cruzi and H. diminuta in the studied sites. Further
studies examining seasonal and geographical patterns could increase our knowledge
on the epidemiology of these pathogens in Mexico and the risk to public health
posed by rodents.
PMID- 28689508
TI - Social inappropriateness in neurodegenerative disorders.
AB - BACKGROUND: New onset of mood and behavioral changes in middle-aged patients are
frequently the first manifestations of an unrecognized neurocognitive disorder.
Impairment of social cognition, the cognitive ability to process social
information coming from others, such as emotions, to attribute mental states to
others, and to respond appropriately to them, is often at the origin of
behavioral manifestations in neurodegenerative disorders. METHODS: This paper
reviews the current literature on social cognition impairment in neurocognitive
disorders, particularly in prodromal stages of behavioral-variant frontotemporal
dementia (bvFTD), Alzheimer's disease (AD), idiopathic Parkinson's disease (IPD),
and Lewy body dementia (LBD). The concepts of social cognition will be reviewed,
including its impairment and neural basis, its clinical assessment, and the
different therapeutic interventions available clinically. RESULTS: Socially
inappropriate behaviors, such as loss of empathy, inappropriateness of affect,
and disinhibition are frequently reported in prodromal bvFTD and in prodromal AD.
Lack of self-control, reduced perception of social cues, such as recognition of
facial emotions and sarcastic speech, and impaired Theory of Mind all contribute
to the neuropsychiatric symptoms and are secondary to neurodegeneration in
specific brain regions. In contrasts to bvFTD and AD, deficits in social
cognition in IPD occur later in the course of the disease and are often
multifactorial in origin. CONCLUSIONS: Through various manifestations, social
inappropriateness is frequently the first clinical sign of a neurodegenerative
process, especially in AD and bvFTD, years before noticeable impairment on
classical neuropsychological assessment and brain atrophy on imaging.
PMID- 28689509
TI - Formononetin, a methoxy isoflavone, enhances bone regeneration in a mouse model
of cortical bone defect.
AB - The bone regeneration and healing effect of formononetin was evaluated in a
cortical bone defect model that predominantly heals by intramembranous
ossification. For this study, female Balb/c mice were ovariectomised (OVx) and a
drill-hole injury was generated in the midfemoral bones of all animals. Treatment
with formononetin commenced the day after and continued for 21 d. Parathyroid
hormone (PTH1-34) was used as a reference standard. Animals were killed at days
10 and 21. Femur bones were collected at the injury site for histomorphometry
studies using microcomputed tomography (MUCT) and confocal microscopy. RNA and
protein were harvested from the region surrounding the drill-hole injury. For
immunohistochemistry, 5 um sections of decalcified femur bone adjoining the drill
hole site were cut. MUCT analysis showed that formononetin promoted bone healing
at days 10 and 21 and the healing effect observed was significantly better than
in Ovx mice and equal to PTH treatment in many aspects. Formononetin also
significantly enhanced bone regeneration as assessed by calcein-labelling
studies. In addition, formononetin enhanced the expression of osteogenic markers
at the injury site in a manner similar to PTH. Formononetin treatment also led to
predominant runt-related transcription factor 2 and osteocalcin localisation at
the injury site. These results support the potential of formononetin to be a bone
healing agent and are suggestive of its promising role in the fracture-repair
process.
PMID- 28689510
TI - Outbreak characteristics associated with identification of contributing factors
to foodborne illness outbreaks.
AB - Information on the factors that cause or amplify foodborne illness outbreaks
(contributing factors), such as ill workers or cross-contamination of food by
workers, is critical to outbreak prevention. However, only about half of
foodborne illness outbreaks reported to the United States' Centers for Disease
Control and Prevention (CDC) have an identified contributing factor, and data on
outbreak characteristics that promote contributing factor identification are
limited. To address these gaps, we analyzed data from 297 single-setting
outbreaks reported to CDC's new outbreak surveillance system, which collects data
from the environmental health component of outbreak investigations (often called
environmental assessments), to identify outbreak characteristics associated with
contributing factor identification. These analyses showed that outbreak
contributing factors were more often identified when an outbreak etiologic agent
had been identified, when the outbreak establishment prepared all meals on
location and served more than 150 meals a day, when investigators contacted the
establishment to schedule the environmental assessment within a day of the
establishment being linked with an outbreak, and when multiple establishment
visits were made to complete the environmental assessment. These findings suggest
that contributing factor identification is influenced by multiple outbreak
characteristics, and that timely and comprehensive environmental assessments are
important to contributing factor identification. They also highlight the need for
strong environmental health and food safety programs that have the capacity to
complete such environmental assessments during outbreak investigations.
PMID- 28689511
TI - Evaluating feasibility and acceptability of a group WHO trans-diagnostic
intervention for women with common mental disorders in rural Pakistan: a cluster
randomised controlled feasibility trial.
AB - AIMS: The aim of this feasibility trial was to evaluate the feasibility and
acceptability of the locally adapted Group Problem Management Plus (PM+)
intervention for women in the conflict affected settings in Swat, Pakistan.
METHODS: This mixed-methods study incorporated a quantitative component
consisting of a two arm cluster randomised controlled feasibility trial, and
qualitative evaluation of the acceptability of the Group PM+ to a range of
stakeholder groups. For the quantitative component, on average from each of the
20 Lady Health Workers (LHWs) catchment area (20 clusters), six women were
screened and recruited for the trial with score of >2 on the General Health
Questionnaire and score of >16 on the WHO Disability Assessment Schedule. These
LHW clusters were randomised on a 1 : 1 allocation ratio using a computer-based
software through a simple randomisation method to the Group PM+ intervention or
Enhanced Usual Care. The Group PM+ intervention consisted of five weekly sessions
of 2 h duration delivered by local non-specialist females under supervision. The
primary outcome was individual psychological distress, measured by levels of
anxiety and depression on the Hospital Anxiety and Depression Scale at 7th week
after baseline. Secondary outcomes include symptoms of depression, post-traumatic
stress disorder (PTSD), general psychological profile, levels of functioning and
generalised psychological distress. Intervention acceptability was explored
through in-depth interviews. RESULTS: The results show that lay-helpers with no
prior mental health experience can be trained to achieve the desired competency
to successfully deliver the intervention in community settings under supervision.
There was a good intervention uptake, with Group PM+ considered useful by
participants, their families and lay-helpers. The outcome evaluation, which was
not based on a large enough study to identify statistically significant results,
indicated statistically significant improvements in depression, anxiety, general
psychological profile and functioning. The PTSD symptoms and depressive disorder
scores showed a trend in favour of the intervention. CONCLUSION: This trial
showed robust acceptance in the local settings with delivery by non-specialists
under supervision by local trained females. The trial paves the way for further
adaptation and exploration of the outcomes through larger-scale implementation
and definitive randomised controlled trials in the local settings.
PMID- 28689512
TI - Circulating miR-23b-3p, miR-145-5p and miR-200b-3p are potential biomarkers to
monitor acute pain associated with laminitis in horses.
AB - Circulating microRNAs (miRNAs) are emerging as promising biomarkers for several
disorders and related pain. In equine practice, acute laminitis is a common
disease characterised by intense pain that severely compromises horse welfare.
Recently, the Horse Grimace Scale (HGS), a facial expression-based pain coding
system, was shown to be a valid welfare indicator to identify pain linked to
acute laminitis. The present study aimed to: determine whether miRNAs can be used
as biomarkers for acute pain in horses (Equus caballus) affected by laminitis;
integrate miRNAs to their target genes and to categorise target genes for
biological processes; gather additional evidence on concurrent validity of HGS by
investigating how it correlates to miRNAs. Nine horses presenting acute laminitis
with no prior treatment were recruited. As control group, nine healthy horses
were further included in the experimental design. Samples were collected from
horses with laminitis at admission before any treatment ('pre-treatment') and 7
days after routine laminitis treatment ('post-treatment'). The expression levels
of nine circulating miRNAs, namely hsa-miR-532-3p, hsa-miR-219-5p, mmu-miR-134
5p, mmu-miR-124a-3p, hsa-miR-200b-3p, hsa-miR-146a-5p, hsa-miR-23b-3p, hsa-miR
145-5p and hsa-miR-181a-5p, were detected and assessed as potential biomarkers of
pain by quantitative PCR using TaqMan(r) probes. The area under the receiver
operating curve (AUC) was then used to evaluate the diagnostic performance of
miRNAs. Molecular data were integrated with HGS scores assessed by one trained
treatment and time point blind veterinarian. The comparative analysis
demonstrated that the levels of miR-23b-3p (P=0.029), miR-145-5p (P=0.015) and
miR-200b-3p (P=0.023) were significantly higher in pre-treatment and the AUCs
were 0.854, 0.859 and 0.841, respectively. MiR-200b-3p decreased after routine
laminitis treatment (P=0.043). Combining two miRNAs in a panel, namely miR-145-5p
and miR-200b-3p, increased efficiency in distinguishing animals with acute pain
from controls. In addition, deregulated miRNAs were positively correlated to HGS
scores. Computational target prediction and functional enrichment identified
common biological pathways between different miRNAs. In particular, the
glutamatergic pathway was affected by all three miRNAs, suggesting a crucial role
in the pathogenesis of pain. In conclusion, the dynamic expression of circulating
miR-23b-3p, miR-145-5p and miR-200b-3p was detected in horses with acute
laminitis and miRNAs can be considered potentially promising pain biomarkers.
Further studies are needed in order to assess their relevancy in other painful
conditions severely compromising horse welfare. An important implication would be
the possibility to use them for the concurrent validation of non-invasive
indicators of pain in horses.
PMID- 28689513
TI - Post-weaning feed efficiency decreased in progeny of higher milk yielding beef
cows.
AB - Current trends in the beef industry focus on selecting production traits with the
purpose of maximizing calf weaning weight; however, such traits may ultimately
decrease overall post-weaning productivity. Therefore, the objective of this
study was to evaluate the effects of actual milk yield in mature beef cows on
their offspring's dry matter intake (DMI), BW, average daily gain, feed
conversion ratio (FCR) and residual feed intake (RFI) during a ~75-day
backgrounding feeding trial. A period of 24-h milk production was measured with a
modified weigh-suckle-weigh technique using a milking machine. After milking,
cows were retrospectively classified as one of three milk yield groups: Lower
(6.57+/-1.21 kg), Moderate (9.02+/-0.60 kg) or Higher (11.97+/-1.46 kg). Calves
from Moderate and Higher milk yielding dams had greater (P<0.01) BW from day 0
until day 75 at the end of the backgrounding feeding phase; however, day 75 BW
were not different (P=0.36) between Lower and Moderate calves. Body weight gain
was greater (P=0.05) for Lower and Moderate calves from the day 0 BW to day 35 BW
compared with Higher calves. Overall DMI was lower (P=0.03) in offspring from
Lower and Moderate cows compared with their Higher milking counterparts. With the
decreased DMI, FCR was lower (P=0.03) from day 0 to day 35 in calves from Lower
and Moderate milk yielding dams. In addition, overall FCR was lower (P=0.02) in
calves from Lower and Moderate milk yielding dams compared with calves from
Higher milk yielding dams. However, calving of Lower milk yielding dams had an
increased (P=0.04) efficiency from a negative RFI value compared with calves from
Moderate and Higher milking dams. Results from this study suggest that increased
milk production in beef cows decreases feed efficiency during a 75-day post
weaning, backgrounding period of progeny.
PMID- 28689514
TI - Room Occupancy-Associated Transmission of MDRO, Clostridium difficile, or
Norovirus: Results From a Room Surveillance Project.
PMID- 28689515
TI - Rapidly progressive heart failure requiring transplantation in muscular
dystrophy: a need for frequent screening.
AB - Fukuyama congenital muscular dystrophy weakens both skeletal and cardiac muscles,
but the rate of cardiomyopathic progression can accelerate faster than that of
skeletal muscles. A 14-year-old boy with Fukuyama congenital muscular dystrophy
presented with mild skeletal myopathy but severe cardiomyopathy requiring heart
transplantation within 1 year of declining heart function. These patients need
frequent screening regardless of musculoskeletal symptoms.
PMID- 28689516
TI - An update on medium- and low-abundant blood plasma proteome of horse.
AB - The main objectives of the study were to: (1) deeply analyse the serum protein
composition of Equus caballus, (2) assess the effectiveness of the high-abundant
protein depletion and improve the concentration of medium- and low-abundant
proteins. The analysis were performed on the blood plasma of three healthy part
Arabian mares. The implementation of two-dimensional electrophoresis and matrix
assisted laser desorption/ionisation - time of flight mass spectrometry allowed
us to establish a horse plasma proteome map. Serum proteins were resolved at pH 4
to 7, followed by 12% SDS-PAGE. As a result 136 spots were successfully
identified, representing the products of 46 unique genes. Of these, 22 gene
products have not been previously identified in horse serum/plasma samples using
proteomic tools. Gene ontology analysis showed that almost 30% of all identified
gene products belong to the coagulation and complement cascades. These results
can undoubtedly serve as a useful and prospective prerequisite for the future
analysis of horse plasma proteome changes in different physiological and
pathophysiological conditions. The use of the medium- and low-abundant protein
enrichment tool increased their abundance and allowed us to identify a higher
number of protein gene products. The highest depletion efficiency was observed
for the most abundant plasma proteins, that is albumin, IgG heavy chains and
serotransferrin.
PMID- 28689517
TI - An assessment of Irish farmers' knowledge of the risk of spread of infection from
animals to humans and their transmission prevention practices.
AB - The aim of this study was to ascertain farmers' knowledge of the risk of spread
of infection from animals to humans, and their transmission prevention practices.
This was a survey of farmers who submitted material to Ireland's Regional
Veterinary Laboratories in 2015. There was an 84% response rate (1044 farmers).
Ninety per cent of farmers were not aware that infection can be acquired from
apparently healthy animals. Over half were not aware that disease could be
contracted from sick poultry or pets. Conversely, the knowledge of the risk to
pregnant women of infection from birthing animals was high (88%). Four-fifths of
farmers sourced drinking water from a private well, and of these, 62% tested
their water less frequently than once a year. Of dairy farmers, 39% drank
unpasteurised milk once a week or more frequently. Veterinarians were the most
commonly cited information source for diseases on farms. The survey findings
indicate that the level of farmers' knowledge and awareness of the spread of
infection from animals to humans is a concern. Further education of the farming
community is needed to increase awareness of both the potential biohazards
present on farms and the practical measures that can be taken to mitigate the
risk of zoonoses.
PMID- 28689518
TI - Colon Cancer Screening - Is It Time Yet?
AB - The month of March is dedicated to Colon Cancer Awareness. Worldwide, colorectal
cancer (CRC) incidence has been on the rise. It is currently the third most
common cancer in men (746,000 cases, 10.0% of the total) and the second in women
(614,000 cases, 9.2% of the total).1 Arecent meta-analysis reported a 61% risk
reduction in CRC incidence with colonoscopy.2 Unlike screening programs for
breast and prostate cancers, not only has CRC screening reduced mortality from
colon cancer and detected early CRC, it has also decreased the incidence of CRC
through detection and removal of pre-cancerous lesions. Studies have shown that
screening for colorectal cancer provided 152 to 313 life-years-gained (LYG) per
1000 forty-year-old individuals.3 Anumber of modalities exist for CRC screening,
which can broadly be categorized into stool-based tests and direct visualization
tests. Stool-based tests include fecal occult blood testing (FOBT), fecal
immunochemical testing (FIT) and stool DNAtesting. Direct visualization tests
include endoscopic procedures such as colonoscopy and flexible sigmoidoscopy; and
radiographic tests such as CT colonography, which has largely replaced air
contrast barium enemas.4 The only reported population-based data for CRC in
Pakistan comes from Bhurgri et al. in 2011.5It described Pakistan as a low risk
region with an age standardized incidence rate (ASR) world per 100,000 of 7.1 in
males and 5.2 in females, but with a much younger age and advanced stage at
diagnosis. The ratio for individuals diagnosed with CRC under the age of 40, as
oppose to over 40 years, was 3:1, which is much higher than the international
average. Noteworthy as well, is an increase in incidence especially among men,
noted between the study periods of 1995-1997 and 1997-2002. It ranks 7th in
incidence among males, and 8th among females, with tobacco related malignancies
topping the list.6 There has since been additional cross-sectional data from
Pakistan echoing these findings of a younger age and advanced disease at
presentation.7 Speaking from a public health perspective, Pakistan, while still
battling communicable diseases, is now seeing an increasing incidence of non
communicable diseases population-based screening programs for CRC were not
justified in most developing countries, citing low reported incidence and low
resource health authorities; but that in limited regions with an ageing
population and a shift to Western lifestyle, organized screening strategies
needed to be developed. This can well be extrapolated to large urban centers in
Pakistan. In a resource poor, conservative country like Pakistan, with poor
health literacy, there exist many barriers to CRC screening which were summed up
very articulately by Ahmed F in 2013. Quite appropriately, areas identified for
further pursuit included, among others, the training of gastroenterologists,
especially female ones, less expensive and more culturally acceptable screening
options, and cost-effectiveness analyses. The recipe for any cancer screening
program to be successful, begins with epidemiological data to document disease
burden. There has not been any population-based cancer registry to report
incidence data for the past few years. There is also no centralized cancer
registry to effectively unify and coordinate data from across the country.
Furthermore, even with a cancer registry there is no mandated reporting of
malignancies from a health policy standpoint, as exists in the more developed
world. The last population-based data we have for CRC was for cases reported
until 2002, and there was already an increase in incidence noted in less than a
decade, starting in 1995.5 Health awareness is another important factor. There is
no data from Pakistan regarding patient or physician awareness regarding colon
cancer. If one is to extrapolate, a cross-sectional study on breast cancer
awareness, for which Pakistan demonstrates one of the highest incidences
worldwide,6 reported that a mammogram had been performed in only 4.9 % of women
in the cohort, while 61.5 % of the remainder had never even heard about it.7 It
is also unclear if we have the infrastructure including endoscopy centers and
adequate numbers of gastroenterologists to service the population at large.
FOBTis available and cheap, but there is no data regarding the availability of
FITor stool DNAtesting. In the absence of health insurance, it will certainly be
a challenge to make CRC screening widely accessible. At what point does a disease
warrant attention? While we may not have the luxury or the immediate necessity to
introduce mass population-based CRC screening, we can certainly start with
individual screening in populations who are at high risk of colorectal cancer due
to family history and have adequate access to healthcare. There should be a
concerted drive to revitalize cancer registration in order to guide health policy
and to have an effective national cancer control program. Awareness programs are
also needed to be established for the public and, specifically, for physicians as
well.
PMID- 28689519
TI - Insulin Resistance and Glucose Levels in Subjects with Subclinical
Hypothyroidism.
AB - OBJECTIVE: To compare insulin resistance and glycemic indicators among subjects
with euthyroidism and subclinical hypothyroidism. STUDY DESIGN: Comparative cross
sectional study. PLACE AND DURATION OF STUDY: Department of Pathology and
Medicine, PNS Hafeez, Islamabad, in collaboration with the Department of Chemical
Pathology and Endocrinology at the Armed Forces Institute of Pathology (AFIP),
Rawalpindi, from December 2015 to September 2016. METHODOLOGY: Subjects referred
for executive screening of apparently healthy population (without any known
history of diabetes, hypertension, heart disease or other chronic ailments), were
included. Subjects were grouped as euthyroidism and subclinical hypothyroidism.
RESULTS: Median (IQR) insulin resistance indices including fasting insulin and
Homeostasis Model Assessment for Insulin Resistance in subjects with group-1
(n=176, 87%, Thyroid Stimulating Hormone: 0.5 - 3.5 mIU/L) and group-2 (n=26,
13%, Thyroid Stimulating Hormone: 3.51 - 15 mIU/L) were 7.6 (6.70) vs. 11.4
(13.72, p=0.040) and 1.77 (1.79) vs. 2.8 (3.07, p=0.071). The median differences
for fasting plasma glucose were 5.0 (1.0) in group-1 vs. 5.0 (1.47) for Group-2
[p=0.618], and glycated hemoglobin was 5.60 (1.1) vs. 5.60 (1.7, p=0.824).
Homeostasis Model Assessment for beta sensitivity index in paradox showed
slightly higher values for group-2 [median (IQR) 86.67 (92.94)] than group-1
[111.6 (189.64, p= 0.040)]. CONCLUSION: Measures of insulin resistance including
Homeostasis Model Assessment for Insulin Resistance and fasting insulin levels
were significantly different between subjects with euthyroidism and having
subclinical hypothyroidism.
PMID- 28689520
TI - Comparison of 12-Hour with 72-Hour Terlipressin Therapy for Bleeding Esophageal
Varices.
AB - OBJECTIVE: To determine the efficacy of 12-hour of Terlipressin therapy as
compared to 72-hour therapy in preventing rebleeding after endoscopic therapy.
STUDY DESIGN: Interventional study. PLACE AND DURATION OF STUDY: Department of
Gastroenterology and Hepatology, Shaikh Zayed Hospital, Lahore, from January to
March 2016. METHODOLOGY: Cirrhotic patients presenting to our hospital with GI
(gastrointestinal) bleeding received Terlipressin 2 mg intravenous bolus,
followed by 1mg 6-hourly until undergoing endoscopy. Those with esophageal
varices as the source of bleeding underwent band ligation and were recruited. Of
the 93 enrolled patients, 90 remained and were randomized into 25 (27.8%) in
control Group-Aand 65 (72.2%) in test Group-B. Group-Areceived 72-hour of
Terlipressin while Group-B received it for 12-hour. Both groups were monitored
for rebleeding for 5 days. RESULTS: Rebleeding occurred in 1 (4%) patient in
Group-Aand 3 (4.6%) in Group-B during the 5-day period. All 4 (4.4%) underwent
repeat endoscopy. The Group-Apatient and 2 (3%) of 3 Group-B patients showed
ulcers over band ligation sites as source of bleed. The third Group-B patient
showed varices requiring repeat banding. One (4%) patient (Group-A) died due to
persistent encephalopathy. No drug related adverse effects were seen. CONCLUSION:
A12-hour duration of Terlipressin as an adjunct to endoscopic band ligation shows
similar results to 72-hour therapy.
PMID- 28689521
TI - Predictive Validity of Family Medicine Resident's Performance at Induction with
Their Future Performance During Residency.
AB - OBJECTIVE: To determine the predictive validity of induction assessment scores of
family medicine residency program for performance in final year of residency.
STUDY DESIGN: Psychometric (predictive-validity) study. PLACE AND DURATION OF
STUDY: The Aga Khan University Hospital, Karachi, from 2008 to 2014. METHODOLOGY:
All family medicine residents were evaluated. Family Medicine Residency induction
assessment scores were used as independent predictor variables, whereas resident
assessment scores during the final year residency program were used as dependent
or outcome variables. Data was analyzed using SPSS version 19. Linear regression
was used to determine predictive validity of induction scores as independent
variables with outcome variables at 95% confidence level. RESULTS: There were 33
residents. MBBS scores accounted for 30.1% of variance in final year Objective
Structured Clinical Exam (OSCE) scores; whereas, induction written test accounted
for 37.1% of variance in final year written test. Induction communication skill
scores did not correlate with in-training communication skill scores or with the
final year OSCE scores. Induction professionalism scores accounted for 13.7% of
the variation in final year OSCE scores, but not with in-training continuous
professionalism scores. CONCLUSION: Induction knowledge scores have acceptable
predictive value for future knowledge and its application. Other valid and
reliable assessment methods, such as multiple mini-interviews, should be explored
for assessment of noncognitive domains at induction.
PMID- 28689522
TI - Efficacy and Toxicity of Concurrent Chemoradiation in Inoperable Oral Carcinoma
in Pakistani Population.
AB - OBJECTIVE: To evaluate the efficacy of concurrent chemoradiation in patients with
locally advanced inoperable squamous cell carcinoma of oral cavity in terms of
local control and toxicity. STUDY DESIGN: Case series. PLACE AND DURATION OF
STUDY: Institute of Nuclear Medicine and Oncology (INMOL), Lahore, from January
2008 to December 2013. METHODOLOGY: Sixty-nine patients with locally advanced
inoperable oral cavity cancer, registered in INMOL hospital from January 2008 to
December 2013 who fulfilled a pre-defined eligibility criteria, were enrolled in
the study. Concurrent chemoradiation protocol consisted of conventional
fractionation delivering 70 Gy with weekly Cisplatin (50 mg/m2) during the course
of radiation. Tumor response was calculated by RECISTcriteria version 1.1 along
with the median overall survival and disease-free survival. Acute treatment
related toxicities were graded as (G). RESULTS: Thirty-six (52.17%) patients
showed complete response; while 19 (27.54%), 8 (11.59%) and 6 (8.7%) were
observed with partial response, stable and progressive disease, respectively.
Treatment response was significant (p<0.001) in terms of responders vs. non
responders to treatment. Median overall survival was 18.00 months; whereas,
median disease-free survival remained 14.00 months. Main toxicities included
mucositis (G3 and G4, 71%), xerostomia (G2 and G3, 82.5%), vomiting (G3 and G4,
51%), myelosuppression (G3 and G4, 26.2%), dermatitis (G3 and G4, 49.2%), and
fatigue (G3 and G4, 57.9%). CONCLUSION: Platinum based CCR Tremained effective
for inoperable oral cancer patients.
PMID- 28689523
TI - Critical Analysis of Piezoelectric Surgery with Oscillating Saw in Bimaxillary
Orthognathic Surgery.
AB - OBJECTIVE: To compare the piezosurgery with conventional saw for osteotomy in
orthognathic bimaxillary surgery. STUDY DESIGN: Comparative study. PLACE AND
DURATION OF STUDY: The Armed Forces Institute of Dentistry, Rawalpindi, Pakistan,
from January 2012 to July 2015. METHODOLOGY: Twenty-four patients, regardless of
gender, were selected for bimaxillary surgery. Each underwent osteotomy with
conventional saw and piezosurgery equipment. Intraoperative and postoperative
parameters, like blood loss during operation, time required for surgery,
postoperative swelling, nerve function, incision and surgical precisons, were
evaluated. RESULTS: Out of total 96 osteotomies, 48 (50%) maxillary and 48 (50%)
mandibular osteotomies were performed. Time required for piezosurgery was more
(63 minutes) as compared to saw (p=0.003). Other parameters, like intraoperative
blood loss (p=0.091), postoperative swelling (p=0.041), and nerve damage
(p=0.009), were far less frequent with piezosurgery than frequent with saw
procedures. CONCLUSION: Piezosurgery is a favourable alternative technique as
compared to saw technique in bimaxillary orthognathic surgeries.
PMID- 28689524
TI - Effects of Supervised Structured Aerobic Exercise Training Program on Interleukin
6, Nitric Oxide Synthase-1, and Cyclooxygenase-2 in Type 2 Diabetes Mellitus.
AB - OBJECTIVE: To determine the effects of supervised structured aerobic exercise
training (SSAET) program on interleukin-6 (IL-6), nitric oxide synthase 1 (NOS
1), and cyclooxygenase-2 (COX-2) in type 2 diabetes mellitus (T2DM). STUDY
DESIGN: Randomized controlled trial. PLACE AND DURATION OF STUDY: Riphah
Rehabilitation and Research Centre, Railways General Hospital, Rawalpindi, from
January 2015 to June 2016. METHODOLOGY: Patients of either gender of minimum one
year history of T2DM ranging from 40-70 years of age were included. Those with
chronic systemic diseases, history of regular exercise, smoking, and those on
dietary plan were excluded. Atotal of 195 patients were screened; 120 were
selected and 102 agreed to participate in the study. They were randomly placed
into experimental and control groups. SSAETprogram, routine medication, and
dietary plan were applied in experimental group; whereas, control group was
managed with routine medication and dietary plan for 25 weeks. IL-6, NOS-1, and
COX-2 were assessed at baseline and 25 weeks. RESULTS: SSAET program, routine
medication and dietary plan showed significantly improved IL-6 (pre-mean=0.25 +/
0.11ng/ml, post-mean=0.19 +/-0.04 ng/ml), NOS-1 (pre-median=4.65 ng/ml, IQ
range=1.04 ng/ml), (post-median=2.72 ng/ml, IQ range=1.60 ng/ml), and COX-2 (pre
mean=18.72 +/-4.42 ng/ml, post-mean=15.18 +/-2.63 ng/ml) in experimental group,
as compared with control group managed by routine medication and dietary plan,
where deterioration was noted in IL-6 (pre-mean=0.23 +/-0.08 ng/ml, post
mean=0.27 +/-0.08 ng/ml) and COX-2 (pre-mean=18.49 +/-4.56 ng/ml, postmean=19.10
+/-4.76 ng/ml), while NOS-1 slight improvement (pre-mean=4.99 ng/ml, IQ
range=2.67 ng/ml), (postmean=4.56 ng/ml, IQ range=3.85 ng/ml). Statistically at
the baseline the p-values were not significant (p>0.05) in both experimental and
control groups for IL-6, COX-2 and NOS-1; while after 25 weeks of intervention,
the experimental group showed significant improvement (p<0.05) in comparison with
the control group. CONCLUSION: SSAET program, routine medication, and dietary
plan had positive effect on IL-6, NOS-1, and COX-2 in T2DM patients.
PMID- 28689525
TI - The Use of Recombinant nAG Protein in Spinal Cord Crush Injury in a Rat Model.
AB - OBJECTIVE: To evaluate the therapeutic properties of nAG protein during the
recovery following acute spinal cord injuries in the rat. STUDY DESIGN: An
experimental study. PLACE AND DURATION OF STUDY: King Saud University, Riyadh,
Saudi Arabia, from September 2014 to September 2015. METHODOLOGY: Eight rats were
studied (4 control rats and 4 experimental rats; and hence 50% were controls and
50% were experimental). All rats were subjected to an acute spinal cord injury
using the aneurysmal clip injury model. Immediately after the injury, a single
intra-dural injection of either normal saline (in the control group) or the nAG
protein (in the experimental group) was done. Assessment of both groups was done
over a 6-week period with regard to weight maintenance, motor recovery scores,
MRI and histopathology of the injury site. RESULTS: Weight maintenance was seen
in the experimental and not in the control rats. Starting at 3 weeks after
injury, the motor recovery was significantly (p<0.05) better in the experimental
group. MRI assessment at 6 weeks showed better maintenance of cord continuity and
less fluid accumulation at the injury site in the nAG-treated group. Just
proximal to the injury site, there was less gliosis in the experimental group
compared to the control group. At the crush injury site, there was less tissue
architecture distortion, less vacuole formation, and less granulation tissue
formation in the experimental group. CONCLUSION: The local injection nAG protein
enhances neuro-restoration, reduces gliosis, and reduces vacuole/ granulation
tissue formation following acute spinal cord crush injury in the rat aneurysmal
clip animal model.
PMID- 28689526
TI - Tension-Free Vaginal Taping in Pakistani Women with Stress Urinary Incontinence.
AB - OBJECTIVE: To evaluate the effectiveness and determine the peroperative and
postoperative complications of tension-free vaginal tape (TVT) sling for urinary
stress incontinence (USI) and contributing factors to complications. STUDY
DESIGN: Descriptive study. PLACE AND DURATION OF STUDY: Kidney Centre
Postgraduate Institute, Karachi, from January 2009 to December 2010. METHODOLOGY:
One hundred consecutive patients underwent TVT as per Ulmsten Technique for
urinary stress incontinence and patients were followed for 3 years. The
subjective cure rate and improvement rate was based on the international
consultation on incontinence questionnaire for evaluating female lower urinary
tract symptoms (ICIQ - FLUS). The subjective cure was defined as the statement of
the woman not experiencing any loss of urine upon physical stress and improvement
rate was defined as occasional leakage during stress. RESULTS: Patients at 1- and
3-year up follow-up showed subjective cure rate and improvement rate of 98% and
2%, and 95% and 5%, respectively. Mean operative time was 32 minutes. UTI was the
commonest complication observed in 7 (7%) patients. Women with voiding
dysfunction preoperatively had 9-fold odds of difficulty postoperatively
(0<0.001). There was a significant association of preoperative symptoms of
overactive bladder (OAB) with the same postoperative symptoms (p<0.0001).
Preoperative hysterectomy had a significant (p< 0.005) 15.63 fold odds of
intraoperative bladder perforation. CONCLUSION: Tension-free vaginal tape sling
is an efficacious and secure surgical procedure for the treatment of urinary
stress incontinence. Bladder perforation, voiding dysfunction, supra-pubic
discomfort and UTI are the commonest complications. Risk factors for perforation
include preoperative hysterectomy. Pre-existing voiding dysfunction and UTI lead
to persistent similar postoperative problems.
PMID- 28689527
TI - Dual Infection by Burkholderia Cepaciaand Pseudomonas Putida in an Infective
Endocarditis Case.
AB - Infective endocarditis is rarely caused by Burkholderia cepacia. Pseudomonas
putidahas not been reported to cause infective endocarditis so far. This is the
first case of infective endocarditis being reported, that is caused by
Pseudomonas putidaand Burkholderia cepaciain an immunocompetent host with no
predisposing factors. Aortic valve replacement surgery was carried out and
antibiotics were given, to which the patient responded well and recovered.
PMID- 28689528
TI - Five-Year Follow-up of a Coronally Advanced Flap Over Grafted Bone and
Restorative Composite in Maxillary Recession Defect.
AB - Periodontal plastic surgery has become a predictable method of managing gingival
recession defects. In the current case report, a five-year follow-up of a
coronally advanced flap surgery with bone graft along with endodontics and fixed
prosthodontic rehabilitation is reported in the maxillary anterior sextant of a
middle aged female. The present case demonstrates that deep and wide gingival
defects can be treated with coronally positioned surgical flap without a
connective tissue graft. Amultidisciplinary management approach was adopted in
this case that yielded predictable outcome.
PMID- 28689529
TI - Multiple Mott Cells in Periapical Lesion of the Oral Cavity.
AB - An entity of bizarre plasma cells has been observed, containing spherical
inclusions of immunoglobulins within the cytoplasm. These cells are termed as
Mott cells and are believed to occur commonly in cases of chronic inflammation.
Until now, they were reported to occur in systemic diseases, various
hematolymphoid malignancies and in some syndromes; but their occurrence in
chronic periapical infections of the oral cavity, given the paucity of available
literature, raises questions about their obscure nature. In the present case
report, a 24-year male presented with a draining sinus and periapical lesion
involving the maxillary right incisors. After clinical and radiographic
examination, an excisional biopsy sample of the periapical lesion was obtained.
Histopathological examination revealed multiple bizarre Mott cells in the
connective tissue stroma. The significance, nature or fate of these Mott cells is
still unknown. Frequently overlooked or a chance occurrence, the presence of
these multiple Mott cells in chronic inflammatory lesions of the oral cavity
could be of some significance and demand increased awareness and further
research.
PMID- 28689530
TI - Congenital Vallecular Cyst: ARare and Potentially Lethal Condition.
AB - Congenital vallecular cyst is a rare laryngeal lesion, accounting for 10-20% of
all laryngeal cysts, with a potential to cause severe upper airway obstruction,
which can be fatal. It can cause stridor, apnea, cyanosis, respiratory distress,
and feeding difficulties. Diagnosis requires a high level of clinical suspicion
and helps in timely intervention. Direct laryngoscopy is gold standard for
definitive diagnosis. Treatment options include aspiration, marsupialization, and
surgical excision. Here, we report a case of 7-week-old infant with complain of
recurrent episodes of cyanosis when agitated, since the age of 3 weeks, admitted
with impression of apparent life-threatening events (ALTEs). Extensive
investigations were non-conclusive, which were done in local hospital. Direct
laryngoscopy was performed in our hospital and showed presence of a vallecular
cyst. Thus complete excision of cyst was done in the same setting with dramatic
relief of symptoms.
PMID- 28689531
TI - Comparison of Lipoprotein Electrophoresis and Apolipoprotein E Genotyping in
Investigating Dysbetalipoproteinemia.
AB - Dysbetalipoproteinemia is often associated with apolipoprotein E2E2 homozygosity;
however, lipoprotein electrophoresis may also be used to assist in the diagnosis.
The aim of this study was to compare apolipoprotein E (apo E) genotyping and
lipoprotein electrophoresis in investigating dysbetalipoproteinemia. Data were
collected over a three-year period from a lipid clinic in a tertiary referral
centre and reviewed for apo E genotyping and lipoprotein electrophoresis. Sixty
two patients had both apo E genotyping and lipoprotein electrophoresis. Of these,
16 patients showed broad beta band on electrophoresis. However, only 3 of them
had apo E2E2 homozygosity on genotyping. Lipoprotein electrophoresis and apo E
genotyping results showed poor concordance. This was primarily due to visual
interpretation error of lipoprotein electrophoresis which may over diagnose
dysbetalipoproteinemia.
PMID- 28689532
TI - Hepatitis C Virus Infection with Multiple Genotypes.
PMID- 28689533
TI - Smooth Muscle Actin: A Confirmatory Immunohistochemical Marker for Myofibroma of
Tongue.
PMID- 28689534
TI - Critical Role of Hardy-Weinberg Equilibrium and Mixed Ethnicity to Avoid
Misinterpretation in Genetic Meta-Analysis Study.
PMID- 28689535
TI - Post-Appendectomy Cecal Prolapse.
PMID- 28689536
TI - Effect of Antibiotics Use During Pregnancy.
PMID- 28689537
TI - Implementation of Quality Measures in Site-Specific Multidisciplinary Tumour
Boards.
PMID- 28689538
TI - ?
PMID- 28689539
TI - ?
PMID- 28689540
TI - [Overfladisk hudnekrose efter perifer intravenos administration af vasoaktive
stoffer].
PMID- 28689541
TI - [Management of unexpected cancer in locally resected colorectal polyps].
AB - Excised colorectal polyps may contain unexpected malignancy. Once diagnosed
histologically, further management is controversial, and little evidence exists
to help in the choice between salvage bowel resection, local resection, systemic
oncological treatment or watchful waiting. Choice of treatment must take patient
related factors as age and co-morbidity into consideration. Clinicians often face
a dilemma concerning further treatment because of the scarce evidence. We want to
establish a suggestion of a tailor-made treatment of malignant colorectal polyps
based on the given evidence.
PMID- 28689542
TI - [Treatment of simple subcutaneous abscesses].
AB - Simple subcutaneous abscesses are common, and we have examined the literature
concerning the ideal treatment of subcutaneous abscesses. We recommend radical
debridement with removal of all pus, the abscess wall and any necrosis. If
primary suture is chosen, preoperative antibiotics should be administered, and
the cavity should be closed without dead space. Antibiotics should not routinely
be given, but always be considered in immunocompromised patients or patients with
septicaemia. Routine examination of the microbiology has no influence on the
treatment and is not recommended.
PMID- 28689543
TI - [Photoscreening of diabetic retinopathy].
AB - Diabetic retinopathy (DR) is the leading cause of blindness in the working-age
population. Screening for DR is indicated to identify patients with sight
threatening DR (proliferative diabetic retinopathy and diabetic macular oedema)
in order to prevent loss of vision. In Denmark, screening is performed by the
private-practicing ophthalmologists or in hospital settings. Annual screening
intervals are often the standard of care, but longer intervals are preferable for
well-controlled patients with no or minimal DR. Automatic screening has the
potential to reduce the human burden of grading.
PMID- 28689544
TI - [Virilisering pa baggrund af meget lille androgenproducerende ovarietumor].
PMID- 28689545
TI - [Partial finger amputation after weever sting and second-degree burn].
AB - The greater weever (Trachinus draco) is the only venomous fish in Denmark, and if
stung by the weever the venom may cause symptoms such as pain, headache, nausea,
dizziness and in severe cases systemic allergic reaction or tissue necrosis. The
venom is heat-labile and should therefore be treated with warm water to the
afflicted area. We report a case of a patient who was stung in the second finger
and because of the treatment, he got a second-degree burn, that may have enhanced
the effect of the venom, thus resulting in partial finger amputation.
PMID- 28689546
TI - [Two cases of the rare Cronkhite-Canada syndrome].
AB - Cronkhite-Canada syndrome (CCS) is a rare non-heritable condition characterized
by gastrointestinal polyposis, dysgeusia, malnutrition, total alopecia and
onychodystrophia. Two Danish cases of CCS (an 88-year-old female and a 69-year
old male) presented with signs of malnutrition, dyspepsia, vomiting, dysgeusia
and hair loss. An upper endoscopy revealed marked oedema and polyposis in the
stomach. Both patients developed colonic adenocarcinomas which were radically
operated. Treatment consisted of hyperalimentation, prednisolone and
azathioprine. Both patients went into remission - the first patient totally.
PMID- 28689547
TI - [The correlation between motivation, emotions land learning].
AB - This article explores the importance of emotions as conditional for motivation in
medical education. The main principles in self-determination theory and in
control-value theory are outlined, and practical consequences which may be drawn
from these theories are discussed. Based on the literature we hypothesize that
human need for autonomy and competence may be violated by strict regulations and
detailed plans for medical education, and that constructive feedback may modify
these potential negative effects and support feelings of competence and autonomy.
PMID- 28689548
TI - [Non-alcoholic fatty liver disease in children and adolescents].
AB - Non-alcoholic fatty liver disease (NAFLD) is characterized by liver fat
accumulation and non-alcoholic steatohepatitis (NASH) with inflammation and
fibrosis, which may lead to cirrhosis also in childhood. NAFLD/NASH in children
are related to obesity and the metabolic syndrome, and incidence and prevalence
are expected to increase. Children having liver steatosis and elevated liver
enzymes are most often asymptomatic, and a liver biopsy is necessary for correct
diagnosis and staging. The treatment should focus on lifestyle changes, as
pharmacological therapy needs further evaluation.
PMID- 28689549
TI - WIC and Breastfeeding.
PMID- 28689550
TI - Historical Perspective of the WIC Program and Its Breastfeeding Promotion and
Support Efforts.
PMID- 28689551
TI - Breastfeeding Is Associated With Reduced Obesity in Hispanic 2- to 5-Year-Olds
Served by WIC.
AB - OBJECTIVE: To examine the relationship between breastfeeding (BF) and odds of
childhood obesity in a large, primarily Hispanic Special Supplemental Nutrition
Program for Women, Infants, and Children (WIC) population. SETTING: A large urban
WIC program in California. PARTICIPANTS: Infants enrolled in WIC born between
2004 and 2007 and observed to age 5 years (N = 39,801; 88.6% Hispanic).
INTERVENTION: Level of BF: fully BF, fully formula feeding, or combination
feeding. MAIN OUTCOME MEASURE: Obesity at age 2-5 years, measured by body mass
index (BMI) >= 95th percentile. ANALYSIS: Logistic regression analyses to
evaluate the association between initiation, duration, and exclusivity of BF and
odds of obesity at age 2-5 years, controlling for ethnicity, preferred language,
family size, poverty level, and maternal BMI. RESULTS: Infants exclusively
formula fed at birth were significantly more likely than fully breastfed infants
to be obese at age 2-5 years (chi2 [2, N = 39,801] = 123.31; P < .001). For every
additional month of any BF, obesity risk at age 2-5 years decreased by 1%. Every
additional month of full BF conferred a 3% decrease in obesity risk. Ethnicity,
preferred language, family size, poverty level, and maternal BMI were also
significantly related to obesity risk. CONCLUSIONS AND IMPLICATIONS:
Breastfeeding may have a role in the attenuation of obesity in early childhood
among Hispanic children. The BF promotion and support offered at WIC may have a
significant role in reducing rates of early childhood obesity.
PMID- 28689552
TI - Breastfeeding is Natural but Not the Cultural Norm: A Mixed-Methods Study of
First-Time Breastfeeding, African American Mothers Participating in WIC.
AB - OBJECTIVE: Identify facilitators, barriers, and needs to increase breastfeeding
(BF) support. DESIGN: Semistructured interviews based on the Theory of Planned
Behavior, Iowa Infant Feeding Attitude Scale, and Breastfeeding Self-Efficacy
Scale-Short Form to measure attitudes and self-efficacy, respectively. SETTING:
One WIC clinic in central Illinois. PARTICIPANTS: First-time BF African American
mothers enrolled in WIC (n = 15). PHENOMENON OF INTEREST: BF facilitators and
barriers in the African American community. ANALYSIS: Descriptive coding and
inductive thematic analysis. RESULTS: Six themes emerged: normative infant
feeding behavior within the sociocultural context; cultural beliefs about
maternal nutrition and BF; time and costs associated with BF; managing and
integrating BF while maintaining a social life; necessity of social support from
significant others and female role models; and suboptimal support from
institutions (hospitals, schools, workplace, and community). A novel finding was
that participants believed that BF was expensive, because they believed that
mothers must eat healthy to breastfeed. In addition, BF was considered natural
but not the cultural norm. Mean Iowa Infant Feeding Attitude Scale score (n = 15)
was 70 (SD = 7), indicating a positive attitude toward BF. Breastfeeding Self
Efficacy Scale-Short Form mean score of 62 indicated a relatively high level of
self-efficacy. CONCLUSIONS AND IMPLICATIONS: Interventions should focus on
providing social support (emotional, tangible, informational, and encouragement)
to African American mothers and their social networks to promote a BF-friendly
environment.
PMID- 28689553
TI - Outcome Evaluation of the You Can Do It Initiative to Promote Exclusive
Breastfeeding Among Women Enrolled in the New York State WIC Program by
Race/Ethnicity.
AB - OBJECTIVE: To evaluate the effectiveness of You Can Do It at improving exclusive
breastfeeding (BF) among New York State women enrolled in Special Supplemental
Nutrition Program for Women, Infants, and Children (WIC). DESIGN: Quasi
experimental study, September, 2013 through February, 2016. SETTING:
Multicomponent intervention paired with a yearlong learning community in 12
clinics. PARTICIPANTS: Women who were enrolled in WIC during the first trimester,
intended to breastfeed or were undecided, and continued in WIC after delivery,
comprised 1 baseline cohort (n = 688) and 2 intervention cohorts: Breastfeeding
Attrition Prediction Tool (BAPT) (consented, n = 362) and non-BAPT (declined, n =
408). INTERVENTION: The BAPT was offered to all eligible women in the
intervention enrollment period. Consenting women received multiple counseling
sessions tailored to individual BAPT results throughout pregnancy and were
contacted promptly after delivery. MAIN OUTCOME MEASURE(S): Prevalence of
exclusive BF at 7, 30, and 60 days. ANALYSIS: Multivariate logistic regression,
stratified by race/ethnicity. Statistical significance set at P < .05. RESULTS:
Prevalence of exclusive BF at 7 and 30 days was significantly higher among BAPT
women compared with non-BAPT or baseline cohorts. Non-Hispanic black and Hispanic
women in the BAPT cohort achieved significantly higher exclusive BF rates at 30
and 60 days compared with those in non-BAPT and baseline cohorts. CONCLUSIONS AND
IMPLICATION: The initiative seems to be effective at increasing exclusive BF,
particularly among non-Hispanic black and Hispanic women in the New York State
WIC program.
PMID- 28689554
TI - Maternal Distraction During Breast- and Bottle Feeding Among WIC and non-WIC
Mothers.
AB - OBJECTIVE: To explore the prevalence and correlates of maternal distraction
during infant feeding within a sample of mothers enrolled or not in the Special
Supplemental Nutrition Program for Woman, Infants, and Children (WIC). DESIGN:
Mothers kept diaries of their infants' feeding patterns. PARTICIPANTS: Mothers (n
= 75) with infants aged <=6 months. MAIN OUTCOME MEASURES: Within the diaries,
mothers recorded what else, if anything, they did during the feeding. Mothers
also completed questionnaires on demographics, feeding styles, and infant
temperament and eating behaviors. ANALYSIS: Mothers' responses were coded into
thematic categories. Feedings were classified as distracted when the mothers
reported doing something other than feeding and/or interacting with the infant.
Logistic regression was used to explore whether mothers exhibited different
levels of distraction when breastfeeding (BF) vs bottle feeding. The researchers
used multiple stepwise regression to explore associations between distracted
feeding and characteristics of mothers and infants. RESULTS: Distractions were
reported during 43% of feedings; 26% involved technological distractors. Mothers
who were multiparous and perceived that their infants had greater appetites
reported greater levels of any distraction during feeding. Mothers who were of
racial/ethnic minorities, adhered to laissez faire feeding style, had younger
infants, and perceived their infants to have lower food responsiveness and
greater appetite reported greater levels of technological distraction. Being
enrolled in WIC was not associated with mothers' levels of distracted feeding.
CONCLUSIONS AND IMPLICATIONS: Mothers reported a wide variety of distractions
during both BF and bottle feeding; higher levels of distraction were associated
with characteristics of both mothers and infants. Further research is needed to
understand whether and how maternal distraction affects feeding outcomes.
Awareness of such distractions and their potential impact would be useful to
practitioners working with pregnant and postpartum women.
PMID- 28689555
TI - Implementing a WIC-Based Intervention to Promote Exclusive Breastfeeding:
Challenges, Facilitators, and Adaptive Strategies.
AB - OBJECTIVE: Understand factors that contributed to the implementation of a
successful multicomponent intervention to promote exclusive breastfeeding (EBF)
within Special Supplemental Nutrition Program for Woman, Infants, and Children
(WIC) clinics. DESIGN: Qualitative study of staff implementers' experiences using
implementation status reports, facilitated group discussion immediately after
implementation, and WIC administrative data. SETTING: WIC staff from 12 clinics
participated in an EBF Learning Community composed of 8 intervention trainings
and ongoing support from trainers and peers. PARTICIPANTS: A total of 47 WIC
staff including 11 directors, 20 other administrators, 8 nutritionists, and 6
peer counselors. INTERVENTION: A WIC-integrated EBF promotion initiative,
supported through a Learning Community, composed of prenatal screening, tailored
trimester-specific counseling, and timely postpartum follow-up. PHENOMENON OF
INTEREST: Challenges and facilitators to implementation within clinics. ANALYSIS:
Iterative qualitative analysis using directed, emergent, and thematic coding.
RESULTS: Implementation experiences were characterized by (1) perceived benefits
of implementation, including improved EBF knowledge and counseling confidence
among staff; and (2) managing implementation, including responding to challenges
posed by clinic settings (resources, routine practices, values, and perceptions
of mothers) through strategies such as adapting clinic practices and intervention
components. CONCLUSIONS AND IMPLICATIONS: Implementation was shaped by clinic
setting and adaptive strategies. Future WIC interventions may benefit from formal
consideration of intervention fit with local clinic setting and allowable
adaptations.
PMID- 28689556
TI - Exploring the Potential for Technology-Based Nutrition Education Among WIC
Recipients in Remote Alaska Native Communities.
AB - OBJECTIVE: Estimate media technology use in Alaska Native communities to inform
the feasibility of technology-based nutrition education. METHODS: A self
administered questionnaire was mailed to a random selection of about 50% of
Special Supplemental Nutrition Program for Women, Infants, and Children (WIC)
authorized representatives in remote Alaska Native communities (n = 975). Media
technology use, interest in media technology-based nutrition education, and
potential barriers were assessed. Chi-square tests were used to investigate
associations among technology use, age, and education. RESULTS: Technology use
was common among respondents (n = 368); use was significantly more common among
younger age groups and participants with a higher level of education. Smartphone
(78.8%) and Facebook (95.8%) use was comparable to national averages, but having
a computer at home (38.4%) was much less likely. Less than 50% of participants
have Internet access at home. CONCLUSIONS AND IMPLICATIONS: Findings shed light
on new opportunities for WIC and other programs to deliver nutrition education to
Alaska Native people in remote communities.
PMID- 28689557
TI - Statewide Breastfeeding Hotline Use Among Tennessee WIC Participants.
AB - OBJECTIVE: To examine the use of the Tennessee Breastfeeding Hotline (TBH), a 24
h/d, 7-d/wk telephonic lactation support program, based on Special Supplemental
Nutrition Program for Women, Infants, and Children (WIC) participation. METHODS:
Self-reported quantitative data were collected during the initial call. Data
collected included caller type, maternal and infant characteristics,
breastfeeding (BF) status, and primary reason for contacting the TBH. RESULTS: A
total of 366 participants in WIC and 1,354 participants not enrolled in WIC
received services through the TBH. Significant differences existed for maternal
age, race, ethnicity, infant age, preterm delivery, caller type, and exclusive BF
(P < .05). Among participants in WIC, lactation professionals primarily addressed
concerns related to lactation and milk expression. CONCLUSIONS AND IMPLICATIONS:
The TBH is a resource to address BF concerns, particularly among women who may
face barriers to seeking professional lactation advice. Special Supplemental
Nutrition Program for Women, Infants, and Children agencies might consider
implementing initiatives outside their standard scope of clinic practice to
address participants' needs for BF support.
PMID- 28689558
TI - New Opportunities for Breastfeeding Promotion and Support in WIC: Review of WIC
Food Packages, Improving Balance and Choice.
AB - Although breastfeeding (BF) is the recommended way to feed infants, this may be
difficult for the low-income women served by the Special Supplemental Nutrition
Program for Women, Infants, and Children (WIC). The 2017 recommended revisions to
the WIC food packages provide substantial support to both exclusively and
partially BF dyads, remove barriers to partial BF choices within the first 30
days postpartum, and increase flexibility in determining the amount of formula
offered to partially breastfed infants. When combined with adequate support and
tailored counseling, these changes are intended to make it easier for women
served by WIC to choose to breastfeed.
PMID- 28689559
TI - Lactation Skills Workshop: A Collaboration of the City of Dallas WIC and Local
Hospitals.
AB - The Baby-Friendly Hospital Initiative, a global endeavor of the World Health
Organization and the United Nations Children's Fund, is an evidence-based program
identifying 10 interventions that when hospitals implement them, breastfeeding
(BF) rates improve. It recognizes the powerful role that health care workers have
in successful BF and the need for competent hands-on skills to support lactation.
The City of Dallas, TX, Special Supplemental Nutrition Program for Women,
Infants, and Children (WIC) program collaborated with 3 urban hospitals and
developed a training of practical techniques and information for staff to use
while working with BF patients. Since implementation, 1,600 workers were trained,
1 hospital achieved Baby-Friendly designation, and all have increased BF rates by
10%.
PMID- 28689560
TI - The Impact of Federal Policy Changes and Initiatives on Breastfeeding Initiation
Rates and Attitudes Toward Breastfeeding Among WIC Participants.
AB - To explore the effects of the Special Supplemental Nutrition Program for Women,
Infants, and Children (WIC) on participants' breastfeeding (BF) practices,
studies that use large national samples are warranted. The US Department of
Agriculture's Food and Nutrition Service funded several studies that leveraged
national samples of WIC agencies, sites, and participants to evaluate how WIC
affects BF outcomes among its participants. This report integrates findings
across multiple Food and Nutrition Service-funded studies to describe important
program benefits and how the program and its benefits supported positive
attitudes and beliefs toward BF, as well as higher rates of BF initiation. The
report concludes with policy implications and suggestions for future research.
PMID- 28689561
TI - Development and Implementation of a Loving Support Makes Breastfeeding Work
Social Media Toolkit for WIC Staff.
PMID- 28689562
TI - Innovative Prenatal Breastfeeding Education Curriculum: Ready, Set, BABY.
PMID- 28689563
TI - Frailty in Older Persons.
AB - Frailty is a clinical state characterized by a decrease of an individual's
homeostatic reserves and is responsible for enhanced vulnerability to endogenous
and/or exogenous stressors. Such a condition of extreme vulnerability exposes
individuals to an increased risk of negative health-related outcomes. Multiple
operational definitions of frailty are available in the literature, but none can
be indicated as a gold standard. Frailty should be considered a condition of
major interest for public health and become the lever for reshaping the obsolete
health care systems currently unable to adequately address the clinical needs of
aging populations.
PMID- 28689564
TI - Sarcopenia.
AB - Sarcopenia refers to age-related muscle loss, defined using a combination of
appendicular muscle mass, muscle strength, and physical performance measures. The
pathogenesis depends on a balance between positive and negative regulators of
muscle growth. Sarcopenia increases the risk for falls, fractures, dependency,
use of hospital services, institutionalization, poor quality of life, and
mortality. In clinical practice, brief screening tools, such as the 5-item SARC-F
score, may be useful. Although pharmacologic treatments are actively being
studied, the current mainstay consists of optimizing nutrition status, in
particular protein and vitamin D status, and resistance exercises.
PMID- 28689565
TI - Anorexia of Aging: Assessment and Management.
AB - Older people often experience loss of appetite and/or decreased food intake that,
unavoidably, impact energy metabolism and overall health status. The association
of age-related nutritional deficits with several adverse outcomes has led to the
recognition of a geriatric condition referred to as "anorexia of aging." Anorexia
is an independent predictor of morbidity and mortality both in the community and
across clinical settings. Multidimensional interventions within personalized care
plans currently represent the most effective option to ensure the provision of
adequate amounts of food, limit weight loss, and prevent adverse health outcomes
in older adults.
PMID- 28689566
TI - Mild Cognitive Impairment.
AB - Mild cognitive impairment (MCI) occurs along a continuum from normal cognition to
dementia. A roadblock to earlier diagnosis and potential treatment is the lack of
consistency with screening for MCI. Universal screening would be ideal, but is
limited. Once a diagnosis of MCI is made, it is important for the clinician to
evaluate for reversible causes. At present time, there are no pharmacologic
treatments proven to slow or cure progression of MCI to dementia; nonetheless,
there is evidence that lifestyle modifications including diet, exercise, and
cognitive stimulation may be effective.
PMID- 28689567
TI - Cognitive Frailty: Mechanisms, Tools to Measure, Prevention and Controversy.
AB - Physical frailty is often associated with cognitive impairment, possibly because
of common underlying pathophysiologic mechanisms. To stimulate research in this
field, the concept cognitive frailty was proposed, emphasizing the important role
of brain aging. Cognitive frailty was defined as the presence of cognitive
deficits in physically frail older persons without dementia. This subtype of
frailty is deemed important, as it may represent a prodromal phase for
neurodegenerative diseases and is potentially a suitable target for early
intervention. The aim of this report is to refine the framework for the
definition and mechanisms of cognitive frailty and relevant screening tools.
PMID- 28689568
TI - Falls in the Aging Population.
AB - The number of people living beyond 65 years of age is increasing rapidly, and
they are at increased risk of falls. Falls-related injuries and hospitalizations
are steadily increasing. Falls can lead to fear of falling, loss of independence,
institutionalization, and death, inevitably posing a significant burden to the
health care system. Therefore, screening of people at risk of falls and
comprehensive assessment of older people at high risk of falls are critical steps
toward prevention. This review evaluates the current knowledge relating to falls,
with particular focus on rapid screening, assessment, and strategies to prevent
falls in the community.
PMID- 28689569
TI - Rapid Geriatric Assessment of Hip Fracture.
AB - A comprehensive geriatric assessment, combined with a battery of imaging and
blood tests, should be able to identify those hip fracture patients who are at
higher risk of short- and long-term complications. This comprehensive assessment
should be followed by the implementation of a comprehensive multidimensional care
plan aimed to prevent negative outcomes in the postoperative period (short and
long term), thus assuring a safe and prompt functional recovery while also
preventing future falls and fractures.
PMID- 28689570
TI - Rapid Depression Assessment in Geriatric Patients.
AB - Depression is common in geriatric patients, especially in those with multiple
comorbidities and polypharmacy. Depression in older adults is often
underdiagnosed and undertreated. Initial screening for depression can easily be
accomplished in the waiting room. Yet the clinical interview still remains the
gold standard for diagnosing geriatric depression. Key components of the clinical
interview are observant watching of the patient for the subtle signs of
depression. Clinical interview should be done with sensitivity to the importance
of privacy. Illicit substances and medical conditions may significantly
contribute. Suicide assessment should be done in a step wise manner.
PMID- 28689571
TI - Dissecting Delirium: Phenotypes, Consequences, Screening, Diagnosis, Prevention,
Treatment, and Program Implementation.
AB - Delirium is an acute change in attention and awareness that preferentially occurs
in older patients with acute illness. This review provides an overview for
clinicians with descriptions of the presentations (phenotypes), consequences,
diagnosis, and screening of delirium. In addition, this review provides guidance
for the challenges posed by delirium in a health care system, including
implementation of delirium programs, tools to address the diagnosis and
differential diagnosis of delirium, and a review of preventive and treatment
studies with a goal of improving clinical practice.
PMID- 28689572
TI - Integrating Quality Palliative and End-of-Life Care into the Geriatric
Assessment: Opportunities and Challenges.
AB - This article provides an overview of how integrating quality palliative and end
of-life care into geriatric assessment can be a tremendous benefit to older adult
patients and their families. Although the quality of palliative and end-of-life
care for older adults has improved greatly, there are still many opportunities to
improve the quality of life and function for older adult patients in the last few
years of their life. More clinical expertise in comprehensive palliative and end
of-life care must be developed and maintained. There also must be greater focus
and more direct reimbursement developed for physicians and health system
providers.
PMID- 28689573
TI - Rapid Geriatric Assessment: Secondary Prevention to Stop Age-Associated
Disability.
AB - The Rapid Geriatric Assessment (RGA) measures frailty, sarcopenia, anorexia,
cognition, and advanced directives. The RGA is a screen for primary care
physicians to be able to detect geriatric syndromes. Early intervention when
geriatric syndromes are recognized can decrease disability, hospitalization, and
mortality.
PMID- 28689574
TI - The New Geriatric Giants.
PMID- 28689575
TI - Retrospective analysis of magnetic resonance imaging for differentiating
intraligamentous leiomyomas from subserosal leiomyomas.
PMID- 28689576
TI - Disseminated intravascular coagulation syndrome two months after conservative
management of placenta accreta. About two patients.
PMID- 28689577
TI - External cephalic version of a breech Twin A is possible.
PMID- 28689578
TI - A systematic investigation of sample diluents in modern supercritical fluid
chromatography.
AB - This paper focuses on the possibility to inject large volumes (up to 10MUL) in
ultra-high performance supercritical fluid chromatography (UHPSFC) under generic
gradient conditions. Several injection and method parameters have been
individually evaluated (i.e. analyte concentration, injection volume, initial
percentage of co-solvent in the gradient, nature of the weak needle wash solvent,
nature of the sample diluent, nature of the column and of the analyte). The most
critical parameters were further investigated using in a multivariate approach.
The overall results suggested that several aprotic solvents including methyl tert
butyl ether (MTBE), dichloromethane, acetonitrile or cyclopentyl methyl ether
(CPME) were well adapted for the injection of large volume in UHPSFC, while MeOH
was generally the worst alternative. However, the nature of the stationary phase
also had a strong impact and some of these diluents did not perform equally on
each column. This was due to the existence of a competition in the adsorption of
the analyte and the diluent on the stationary phase. This observation introduced
the idea that the sample diluent should not only be chosen according to the
analyte but also to the column chemistry to limit the interactions between the
diluent and the ligands. Other important characteristics of the "ideal" SFC
sample diluent were finally highlighted. Aprotic solvents with low viscosity are
preferable to avoid strong solvent effects and viscous fingering, respectively.
In the end, the authors suggest that the choice of the sample diluent should be
part of the method development, as a function of the analyte and the selected
stationary phase.
PMID- 28689579
TI - Characterization of a dicationic imidazolium-based ionic liquid as a gas
chromatography stationary phase.
AB - Here we report the characteristics of a new synthesized ionic liquid, 1,9-di(N
naphthalen-2-ylimidazolium)nonane bis[(trifluoromethyl)sulfonyl]imide
([C9(2NPTim)2][(NTf2)2]), as a stationary phase by inverse gas chromatography.
The McReynolds constants demonstrated that the [C9(2NPTim)2][(NTf2)2] had an
average polarity of 667 and polarity number P.N.=75, suggesting its polar nature.
The solvation properties of the new stationary phase were determined by the
calculation of Abraham solvation system constants, whereby the results showed
that its major interactions with the analytes included H-bond basicity (a),
dipole-dipole (s) and dispersive (l) interactions. The activity coefficients
(gammainfinity) and selectivities (SIJinfinity) at infinite dilution were also
determined for various polar and nonpolar organic solutes at different
temperatures. The separation performance of the [C9(2NPTim)2][(NTf2)2] stationary
phase was evaluated by GC separations of different analytes, including normal
alkanes and aromatic compounds. The TGA results showed that the stationary phase
had high thermal stability up to 420 degrees C.
PMID- 28689580
TI - A molecular modeling based method to predict elution behavior and binding patches
of proteins in multimodal chromatography.
AB - Multimodal (MM) chromatography provides a powerful means to enhance the
selectivity of protein separations by taking advantage of multiple weak
interactions that include electrostatic, hydrophobic and van der Waals
interactions. In order to increase our understanding of such phenomena, a
computationally efficient approach was developed that combines short molecular
dynamics simulations and continuum solvent based coarse-grained free energy
calculations in order to study the binding of proteins to Self Assembled
Monolayers (SAM) presenting MM ligands. Using this method, the free energies of
protein-MM SAM binding over a range of incident orientations of the protein can
be determined. The resulting free energies were then examined to identify the
more "strongly bound" orientations of different proteins with two multimodal
surfaces. The overall free energy of protein-MM surface binding was then
determined and correlated to retention factors from isocratic chromatography.
This correlation, combined with analytical expressions from the literature, was
then employed to predict protein gradient elution salt concentrations as well as
selectivity reversals with different MM resin systems. Patches on protein
surfaces that interacted strongly with MM surfaces were also identified by
determining the frequency of heavy atom contacts with the atoms of the MM SAMs. A
comparison of these patches to Electrostatic Potential and hydrophobicity maps
indicated that while all of these patches contained significant positive charge,
only the highest frequency sites also possessed hydrophobicity. The ability to
identify key binding patches on proteins may have significant impact on process
development for the separation of bioproduct related impurities.
PMID- 28689581
TI - Assessment of intra-particle diffusion in hydrophilic interaction liquid
chromatography and reversed-phase liquid chromatography under conditions of
identical packing structure.
AB - A recently developed stripping protocol to completely remove the stationary phase
of reversed-phase liquid chromatography (RPLC) columns and turn them into
hydrophilic interaction liquid chromatography (HILIC) columns with identical
packing characteristics is used to study the underlying mechanisms of intra
particle diffusion in RPLC and HILIC. The protocol is applied to a column with a
large geometrical volume (250*4.6mm, 5MUm) to avoid extra-column effects and for
compounds with a broad range in retention factors (k" from ~0.6 to 8). Three
types of behavior for the intra-particle diffusion (Dpart/Dm) in RPLC versus
HILIC can be distinguished: for nearly unretained compounds (k"<0.6), intra
particle diffusion in HILIC is larger than in RPLC; for compounds with
intermediate retention behavior (k"~0.9-1.2), intra-particle diffusion in HILIC
and RPLC are similar; and for well retained compounds (k">1.8), intra-particle
diffusion in RPLC is larger than in HILIC. To explain these observations,
diffusion in the stationary phase (gammasDs) and in the stagnant mobile phase in
the mesopore zone (gammampDm) are deduced from experimentally determined values
of the intra-particle diffusion, using models derived from the Effective Medium
Theory. It is demonstrated that the larger intra-particle diffusion obtained for
slightly retained compounds under HILIC conditions is caused by the higher
mesopore diffusion in HILIC (gammamp=0.474 for HILIC versus 0.435 for RPLC),
while the larger intra-particle diffusion obtained for strongly retained
compounds under RPLC conditions can be related to the much higher stationary
phase diffusion in RPLC (gammasDs/Dm=0.200 for RPLC versus 0.113 for HILIC).
PMID- 28689582
TI - Evaluation of hydrophilic interaction liquid chromatography stationary phases for
analysis of opium alkaloids.
AB - The separation of a mixture containing five major opium alkaloids, namely
morphine, codeine, thebaine, noscapine and papaverine has been investigated in
hydrophilic interaction liquid chromatography (HILIC) mode using five different
stationary phases: bare silica, zwitterion, aminopropyl, diol and cyanopropyl. In
order to propose the appropriate column for separation and purification,
retention behaviors of the five natural opioids have been studied on mentioned
HILIC stationary phases. The mechanism of separation in diverse HILIC media,
based on the formation of water-rich layer on surface of the HILIC stationary
phases and the physicochemical properties of opium alkaloids, such as pKa (acidic
pK) and the octanol-water distribution coefficient (log Do/w) are discussed.
Chromatographic responses including modified limit of detection LODm, signal to
noise ratio (S/N)m, and defined modified RSm have considered for suggestion of
the suitable column for quantitative/qualitative and preparative purposes.
According to the obtained results, diol stationary phase is best suited for
analytical chromatography, whereas bare silica and zwitterionic stationary phases
are appropriate for preparative applications.
PMID- 28689583
TI - Best practice guidelines for modern statistical methods in applied clinical
research: Introduction to the Special Section.
PMID- 28689584
TI - Hepatitis C Infection: A Systemic Disease
AB - It is critical to recognize that hepatitis C virus (HCV) infection is, in fact, a
multifaceted systemic disease with both hepatic and extrahepatic complications.
It is also important to recognize that the comprehensive burden of HCV should
include not only its clinical burden but also its burden on the economic and
patient-reported outcomes. It is only through this comprehensive approach to HCV
infection that we can fully appreciate its true burden and understand the full
benefit of curing HCV for the patient and the society.
PMID- 28689585
TI - Rheumatologic Manifestations of Hepatitis C Virus Infection.
AB - Hepatitis C virus (HCV) infection is associated with a morbidity and mortality
due to liver complications. HCV infection is also frequently associated with
rheumatic disorders, such as arthralgia, myalgia, cryoglobulinemia vasculitis,
and sicca syndrome, as well as the production of autoantibodies. The treatment of
HCV infection with interferon alpha (IFN) has been contraindicated for a long
time in many rheumatologic autoimmune/inflammatory disorders. New oral IFN-free
combinations offer an opportunity for HCV-infected patients with extrahepatic
manifestations, including rheumatologic autoimmune/inflammatory disorders, to be
cured with a short treatment duration and a low risk of side effects.
PMID- 28689586
TI - Cardiovascular Manifestations of Hepatitis C Virus.
AB - Hepatitis C virus (HCV) infection is a prevalent condition associated with
numerous extrahepatic manifestations. Epidemiologic studies have found that HCV
is associated with increased cardiovascular morbidity and mortality, in
particular with carotid atherosclerosis, cerebrovascular events, and coronary
heart disease. The mechanisms involved encompass a chronic systemic inflammatory
state, insulin resistance, and a potential, direct infection of the vascular
endothelium. Sustained virologic response with interferon-based regimens is
associated with reduced cardiovascular events, although this must be validated
with newer direct-acting antivirals. This clear association between HCV and
cardiovascular events may have significant economical and public health
implications.
PMID- 28689587
TI - Metabolic Manifestations of Hepatitis C Virus: Diabetes Mellitus, Dyslipidemia.
AB - Metabolic disorders are common in patients with chronic hepatitis C virus (HCV)
infection. Epidemiologic and clinical data indicate an overprevalence of lipids
abnormalite, steatosis, insuline resistance (IR) and diabetes mellitus in HCV
patients, suggesting that HCV itself may interact with glucido-lipidic
metabolism. HCV interacts with the host lipid metabolism by several mechanisms
leading to hepatic steatosis and hypolipidemia which are reversible after viral
eradication. Liver and peripheral IR are HCV genotype/viral load dependent and
improved after viral eradication. This article examines examine the relationship
between HCV, lipid abnormalities, steatosis, IR, and diabetes and the pathogenic
mechanisms accounting for these events in HCV-infected patients.
PMID- 28689588
TI - Renal Manifestations of Hepatitis C Virus.
AB - Hepatitis C virus (HCV) is a hepatotropic and lymphotropic virus responsible for
hepatic and extrahepatic autoimmune and neoplastic disorders, including renal
involvement, which is the consequence of immune-mediated organ damage due to
glomerular deposition of immune-complex and/or anti-HCV IgG antibodies and
complement. It can appear at any time during the natural history of HCV
infection, more often as membranoproliferative glomerulonephritis, alone or in
association with other HCV-related disorders. The presence of renal involvement
should be investigated in HCV-infected individuals at the first referral and
during clinical follow-up.
PMID- 28689590
TI - Chronic Hepatitis C Virus Infection and Depression.
AB - Hepatitis C virus (HCV) infection is a systemic disease with hepatic and
extrahepatic manifestations, including neuropsychiatric conditions. Depression is
a frequent disorder, which has been reported in one-third of patients with HCV
infection and has an estimated prevalence of 1.5 to 4.0 times higher than that
observed in patients with chronic hepatitis B virus infection or the general
population. HCV seems to play a direct and indirect role in the development of
depression. Impaired quality of life and increasing health care costs have been
reported for patients with HCV infection with depression. Treatment-induced HCV
clearance has been associated with improvement of depression and quality of life.
PMID- 28689589
TI - Hepatitis C Virus-Associated Non-Hodgkin Lymphomas: Biology, Epidemiology, and
Treatment.
AB - Eradication of hepatitis C virus (HCV) in indolent non-Hodgkin lymphomas (NHLs),
especially in marginal zone lymphomas, determines the regression of the
hematologic disorder in a significant fraction of cases. Because direct antiviral
agents show an excellent profile in terms of efficacy, safety, and rapid onset of
action, these drugs can be used in any clinical situation and in the presence of
any comorbidities. To avoid the progression of the NHL, despite HCV eradication,
antiviral therapy should be provided as soon as the viral infection is
discovered; before that, the chronic antigenic stimulation determines the
irreversible proliferation of neoplastic B cells.
PMID- 28689591
TI - Neurologic Manifestations of Hepatitis C Virus Infection.
AB - The extrahepatic manifestations of hepatitis C include effects on the central
nervous system, which have been associated with the ability of hepatitis C virus
(HCV) to replicate in microglial and endothelial cells and the chronic
inflammation induced by HCV. HCV can induce impaired neurocognition, which is
clinically manifested by impaired quality of life, fatigue, and brain fog. These
cognitive defects can be present even in patients with mild histologic HCV and
have been confirmed by neurocognitive testing and brain imaging by magnetic
resonance spectroscopy. Neurocognitive defects include loss of functioning memory
and subtle changes in attention and processing speed.
PMID- 28689592
TI - Hepatitis C and Risk of Nonhepatic Malignancies.
AB - Epidemiologic studies show an increased risk of mortality among hepatitis C virus
(HCV)-infected individuals compared with uninfected individuals from hepatic and
nonhepatic causes. This article reviews the biologic plausibility of and
epidemiologic evidence for the association between HCV and five extrahepatic
malignancies: cholangiocarcinoma (CCA), pancreatic adenocarcinoma, papillary
thyroid cancer, oral squamous cell cancer, and renal/kidney cancer. There is
sufficient evidence to suggest that HCV is associated with intrahepatic CCA. The
evidence for the link between HCV and pancreatic adenocarcinoma, oral squamous
cell cancer, and renal/kidney cancer is compelling but requires further study.
Based on available studies, there is no significant association between HCV,
extrahepatic CCA, and papillary thyroid cancer.
PMID- 28689593
TI - Dermatologic Manifestations of Chronic Hepatitis C Infection.
AB - Chronic hepatitis C virus (HCV) infection is associated with various extrahepatic
manifestations, including dermatologic involvement mostly caused by immune
complexes. Mixed cryoglobulinemia has a strong relationship with HCV with 95% of
these patients being infected with HCV. Lichen planus is a disease of the
squamous epithelium and may affect any part of the skin, with 4% to 24% of
patients with lichen planus reported to have chronic HCV infection. Porphyria
cutanea tarda is the most common form of porphyria, and it is thought that HCV
interferes with iron stores, which can promote porphyria cutanea tarda. Finally,
necrolytic acral erythema is a rare, psoriasis-like disease closely associated
with HCV.
PMID- 28689594
TI - Patient-Reported Outcomes and Fatigue in Patients with Chronic Hepatitis C
Infection.
AB - Fatigue is a common symptom. Diagnosis is difficult. Fatigue is often a complex
symptom. In the recent years, fatigue has gained considerable amount of
attention. It has 2 major types, central and peripheral, which may occur together
or alone. Although fatigue has many strong relations with depression and sleep
disorders, it is a separate entity. For the diagnosis of fatigue, self-reports
and patient-reported outcomes are highly valuable tools because these methods can
reflect patients' perceptions. Treating the underlying disease with newly
developed direct-acting antivirals often improves the perceived fatigue. Healthy
lifestyle changes are the cornerstone of the treatment.
PMID- 28689595
TI - Economic Burden of Hepatitis C Infection.
AB - The economic burden of chronic hepatitis C might exceed $10 billion annually in
the United States alone. This disease has a worldwide prevalence of up to 3%,
making the global burden of the disease comparably tremendous. The cost of the
disease includes direct medical expenses for its hepatic and extrahepatic
manifestations, and also indirect costs incurred from impaired quality of life
and the loss of work productivity. Recent emergence of treatment options that are
not only highly effective and safe but also costly has emphasized the need to
study the disease from the economic point of view.
PMID- 28689596
TI - Extrahepatic Manifestations of Hepatitis C Virus After Liver Transplantation.
AB - Chronic hepatitis C virus (HCV) infection remains a leading cause of chronic
liver disease in the United States. Although the hepatic impact of chronic HCV
leading to cirrhosis and the need for liver transplantation is paramount, the
extrahepatic manifestations of chronic HCV infection are equally important. In
particular, a better understanding of the prevalence and impact of extrahepatic
manifestations of chronic HCV infection in the post-liver transplant setting
relies on understanding the interplay between the effects of chronic HCV
infection in a posttransplant environment characterized by strong
immunosuppression and the associated risks of this milieu.
PMID- 28689597
TI - Other Extrahepatic Manifestations of Hepatitis C Virus Infection (Pulmonary,
Idiopathic Thrombocytopenic Purpura, Nondiabetes Endocrine Disorders).
AB - Extrahepatic manifestations of hepatitis C virus (HCV) infection are a rare but
serious condition. This article summarizes the current literature on the
association between HCV and endocrine and pulmonary manifestations, as well as
idiopathic thrombocytopenic purpura (ITP). HCV may directly infect extrahepatic
tissues and interact with the immune system predisposing for obstructive and
interstitial lung disease, ITP, autoimmune thyroiditis, infertility, growth
hormone and adrenal deficiencies, osteoporosis, and potentially lung and thyroid
cancers. However, in many cases, the current evidence is divergent and cannot
sufficiently confirm a true association, which emphasizes the need for future
targeted projects in this field.
PMID- 28689598
TI - Treatment of Extrahepatic Manifestations of Hepatitis C Virus.
AB - Chronic infection with hepatitis C virus (HCV) is a multifaceted disease
characterized by many extrahepatic manifestations (EHMs) that affect outcome and
quality of life. HCV eradication by antiviral treatment has been proved
beneficial in preventing the development of EHMs and is also able to improve many
HCV-related severe disorders and neurocognitive outcomes and quality of life.
Until recently, antiviral therapy of EHMs was limited to the presence of
interferon-based treatment, and was contraindicated in many patients because of
hematologic toxicity or risk of exacerbating immune-mediated disorders. The
availability of interferon-free regimens solves this issue allowing for enhanced
safety and efficacy to provide universal treatment of HCV-related EHMs.
PMID- 28689599
TI - Preface.
PMID- 28689600
TI - Meditation and the brain - Neuronal correlates of mindfulness as assessed with
near-infrared spectroscopy.
AB - Mindfulness meditation as a therapeutic intervention has been shown to have
positive effects on psychological problems such as depression, pain or anxiety
disorders. In this study, we used functional near-infrared spectroscopy (fNIRS)
to detect differences in hemodynamic responses of meditation experts (14
participants) and a control group (16 participants) in a resting and a
mindfulness condition. In both conditions, the sound of a meditation bowl was
used to find group differences in the auditory system and adjacent cortical
areas. Different lateralization patterns of the brain were found in expert
meditators while being in a resting state (amplified left hemisphere) or being in
mindfulness state (amplified right hemisphere). Compared to the control group,
meditation experts had a more widespread pattern of activation in the auditory
cortex, while resting. In the mindfulness condition, the control group showed a
decrease of activation in higher auditory areas (BA 1, 6 and 40), whereas the
meditation experts had a significant increase in those areas. In addition,
meditation expert had highly activated brain areas (BA 39, 40, 44 and 45) beyond
the meditative task itself, indicating possible long-term changes in the brain
and their positive effects on empathy, meta cognitive skills and health.
PMID- 28689601
TI - Imaging features of intracranial psammomatous meningioma.
AB - PURPOSE: This study was conducted to describe the imaging features of
intracranial psammomatous meningioma (IPM). MATERIALS AND METHODS: Twenty-three
patients with a histopathological diagnosis of IPM between January 2007 and
August 2016 were retrospectively reviewed. Twenty-two patients underwent contrast
enhanced MRI scanning, and 16 underwent non-enhanced CT. RESULTS: A total of 23
adult patients (3 men, 20 women; mean age, 55.3+/-7.0 years) with 30 IPMs,
including 3 patients with multiple IPMs, were recruited. Twenty tumours (66.7%)
were located at the cerebral convexity. The mean size of the lesions was 2.42+/
0.92cm (range, 1.2-4.8cm). All tumours had a regular shape. On CT scans, 13
masses (13/22) were totally replaced with calcifications, and calcifications were
observed in 21 cases (21/22) with higher density. There were 22 cases (22/30) of
IPMs presenting adjacent hyperostosis, while 8 cases (8/30) presented no skull
changes that were not close to the skull. Nearly half of the cases (14/29) showed
mixed hypo- and hyperintensity on T2-weighted images and DWI. PTBE was present in
8 tumours and absent in the other 22, among which only 4 tumours were accompanied
by severe oedema. CONCLUSIONS: These radiological findings may facilitate correct
diagnosis for IPMs and thus presurgical planning, prognosis evaluation and
treatment of meningiomas.
PMID- 28689602
TI - Preparation and efficacy assessment of malva nut polysaccharide for skin
hydrating products.
AB - INTRODUCTION: Scaphium scaphigerum or malva nut has long been served in Chinese
medicine. However, the use of this herb in modern health care applications has,
to date, been rarely reported. MATERIALS AND METHODS: Maceration of the herb in
water afforded malva nut polysaccharide which was standardized. Safety and skin
hydrating efficacy of the polysaccharide and products were evaluated in human
volunteers. RESULTS: Malva nut polysaccharide (41.71+/-0.64%) having 36.58+/
0.51% total sugar content was isolated, with further analysis quantifying ash,
carbohydrate, reducing sugar and moisture contents to be 6.05+/-0.00, 40.06+/
1.00, 12.20+/-0.05 and 12.64+/-0.31%, respectively. The polysaccharide exhibited
swelling and hydrating capacities of 0.46+/-0.01% and 54.46+/-0.02g/g, with L*,
a* and b* of 52.56+/-0.04, 9.02+/-0.06 and 18.42+/-0.03, respectively, and a
viscosity of 1263.00+/-2.00 cps. Accelerated testing indicated the
biopolysaccharide to be stable, resulting in no skin irritation in 15 human
volunteers. The skin hydrating efficacy as assessed via a randomized single
blind, placebo-controlled study in 24 volunteers highlighted the superior
performance of malva nut over the vehicle (moisture retainment for 70min as
examined by Corneometer(r) CM 825). A stable skin moisturizing gel containing
malva nut was developed and was shown to exhibit improved performance over
benchmark tamarind and algae polysaccharide gels (after 180min observation).
CONCLUSION: Malva nut polysaccharide has potential as a key ingredient in skin
hydrating products, which should encourage its further development.
PMID- 28689603
TI - Small bowel dilation in children with short bowel syndrome is associated with
mucosal damage, bowel-derived bloodstream infections, and hepatic injury.
AB - BACKGROUND: Liver disease occurs frequently in short bowel syndrome. Whether
small bowel dilation in short bowel syndrome could influence the risk of liver
injury through increased bacterial translocation remains unknown. Our aim was to
analyze associations between small bowel dilation, mucosal damage, bloodstream
infections, and liver injury in short bowel syndrome patients. METHODS: Among
short bowel syndrome children (n = 50), maximal small bowel diameter was measured
in contrast series and expressed as the ratio to the height of the fifth lumbar
vertebra (small bowel diameter ratio), and correlated retrospectively to fecal
calprotectin and plasma citrulline-respective markers of mucosal inflammation and
mass-bloodstream infections, liver biochemistry, and liver histology. RESULTS:
Patients with pathologic small bowel diameter ratio >2.17 had increased fecal
calprotectin and decreased citrulline (P < .04 each). Of 33 bloodstream
infections observed during treatment with parenteral nutrition, 16 were caused by
intestinal bacteria, cultured 15 times more frequently when small bowel diameter
ratio was >2.17 (P < .001). Intestinal bloodstream infections were predicted by
small bowel diameter ratio (odds ratio 1.88, P = .017), and their frequency
decreased after operative tapering procedures (P = .041). Plasma bilirubin
concentration, gamma-glutamyl transferase activity, and histologic grade of
cholestasis correlated with small bowel diameter ratio (0.356-0.534, P < .014
each), and were greater in the presence of intestinal bloodstream infections (P <
.001 for all). Bloodstream infections associated with portal inflammation,
cholestasis, and fibrosis grades (P < .031 for each). In linear regression,
histologic cholestasis was predicted by intestinal bloodstream infections, small
bowel diameter ratio, and parenteral nutrition (beta = 0.36-1.29; P < .014 each),
while portal inflammation by intestinal bloodstream infections only (beta = 0.62;
P = .033). CONCLUSION: In children with short bowel syndrome, small bowel
dilation correlates with mucosal damage, bloodstream infections of intestinal
origin, and cholestatic liver injury. In addition to parenteral nutrition, small
bowel dilation and intestinal bloodstream infections contribute to development of
short bowel syndrome-associated liver disease.
PMID- 28689604
TI - Outcomes of hospitalized patients undergoing emergency general surgery remote
from admission.
AB - BACKGROUND: Emergency general surgery during hospitalization has not been well
characterized. We examined emergency operations remote from admission to identify
predictors of postoperative 30-day mortality, postoperative duration of stay >30
days, and complications. METHODS: Patients >18 years in The American College of
Surgeons National Surgical Quality Improvement Program (2011-2014) who had 1 of 7
emergency operations between hospital day 3-18 were included. Patients with
operations >95th percentile after admission (>18 days; n = 581) were excluded.
Exploratory laparotomy only (with no secondary procedure) represented either
nontherapeutic or decompressive laparotomy. Multivariable logistic regression was
used to identify predictors of study outcomes. RESULTS: Of 10,093 patients with
emergency operations, most were elderly (median 66 years old [interquartile
ratio: 53-77 years]), white, and female. Postoperative 30-day mortality was 12.6%
(n = 1,275). Almost half the cohort (40.1%) had a complication. A small subset
(6.8%) had postoperative duration of stay >30 days. Postoperative mortality after
exploratory laparotomy only was particularly high (>40%). In multivariable
analysis, an operation on hospital day 11-18 compared with day 3-6 was associated
with death (odds ratio 1.6 [1.3-2.0]), postoperative duration of stay >30 days
(odds ratio 2.0 [1.6-2.6]), and complications (odds ratio 1.5 [1.3-1.8]).
Exploratory laparotomy only also was associated with death (odds ratio 5.4 [2.8
10.4]). CONCLUSION: Emergency general surgery performed during a hospitalization
is associated with high morbidity and mortality. A longer hospital course before
an emergency operation is a predictor of poor outcomes, as is undergoing
exploratory laparotomy only.
PMID- 28689606
TI - Targeting Influencers of Behavior in Nutrition Education.
PMID- 28689607
TI - Best Papers for 2016.
PMID- 28689605
TI - Circadian Disruptions in the Myshkin Mouse Model of Mania Are Independent of
Deficits in Suprachiasmatic Molecular Clock Function.
AB - BACKGROUND: Alterations in environmental light and intrinsic circadian function
have strong associations with mood disorders. The neural origins underpinning
these changes remain unclear, although genetic deficits in the molecular clock
regularly render mice with altered mood-associated phenotypes. METHODS: A
detailed circadian and light-associated behavioral characterization of the Na+/K+
ATPase alpha3 Myshkin (Myk/+) mouse model of mania was performed. Na+/K+-ATPase
alpha3 does not reside within the core circadian molecular clockwork, but Myk/+
mice exhibit concomitant disruption in circadian rhythms and mood. The neural
basis of this phenotype was investigated through molecular and
electrophysiological dissection of the master circadian pacemaker, the
suprachiasmatic nuclei (SCN). Light input and glutamatergic signaling to the SCN
were concomitantly assessed through behavioral assays and calcium imaging.
RESULTS: In vivo assays revealed several circadian abnormalities including
lengthened period and instability of behavioral rhythms, and elevated metabolic
rate. Grossly aberrant responses to light included accentuated resetting,
accelerated re-entrainment, and an absence of locomotor suppression.
Bioluminescent recording of circadian clock protein (PERIOD2) output from ex vivo
SCN revealed no deficits in Myk/+ molecular clock function. Optic nerve crush
rescued the circadian period of Myk/+ behavior, highlighting that afferent inputs
are critical upstream mediators. Electrophysiological and calcium imaging SCN
recordings demonstrated changes in the response to glutamatergic stimulation as
well as the electrical output indicative of altered retinal input processing.
CONCLUSIONS: The Myshkin model demonstrates profound circadian and light
responsive behavioral alterations independent of molecular clock disruption.
Afferent light signaling drives behavioral changes and raises new mechanistic
implications for circadian disruption in affective disorders.
PMID- 28689608
TI - Cooking Matters for Adults Improves Food Resource Management Skills and Self
confidence Among Low-Income Participants.
AB - OBJECTIVE: Determine the impact of Cooking Matters for Adults (CM) on food
resource management (FRM) skills and self-confidence 6 months after course
completion. DESIGN: Quasi-experimental design with nonequivalent comparison group
and 6-month follow-up. SETTING: Cooking Matters for Adults programs in CA, CO,
ME, MA, MI, and OR. PARTICIPANTS: Participants in CM attending classes in April
to July, 2016 (n = 332); comparison group (n = 336). INTERVENTION: Cooking
Matters for Adults educated low-income adults to shop for and prepare healthy
meals economically using hands-on meal preparation, facilitated discussion, and
an interactive grocery store tour. Classes met for 2 hours, once a week for 6
weeks. MAIN OUTCOME MEASURE(S): Food resource management practices; FRM self
confidence (ie, in shopping for and preparing healthy foods on a budget);
worrying that food might run out. ANALYSIS: Pearson's chi-square test and t tests
identified measures associated with outcomes of interest and between-group
differences. Repeated-measures linear mixed models with fixed and random effects
were used to examine differences in outcomes between participants in CM and
nonequivalent comparison group and to estimate the treatment effect of the
program at 3 and 6 months after course completion. RESULTS: Six months after
course completion, CM participants demonstrated improvements in all outcome
measures of interest: Use of FRM practices improved (P = .002) as did FRM
confidence (P < .001). Participants also worried less that food would run out
before they had money to buy more (P = .03). CONCLUSIONS AND IMPLICATIONS: This
study demonstrated a positive impact of including FRM skills and confidence
building in a nutrition education program, the effects of which could be seen for
6 months after participation in the program. Equipping low-income families with
FRM skills allowed them to access healthier foods even during times of hardship.
PMID- 28689609
TI - Parental History of Disruptive Life Events and Household Food Insecurity.
AB - OBJECTIVE: To investigate whether a history of disruptive life events (ie, school
suspension or expulsion, job termination, hospitalization for mental health,
and/or criminal justice involvement) among parents is positively associated with
household food insecurity. DESIGN: Structured interviews and self-report surveys.
SETTING: Households across all 50 states in the US. PARTICIPANTS: Subsample of
6,270 households that participated in the Early Childhood Longitudinal Study
Birth Cohort with valid maternal and paternal data. MAIN OUTCOME MEASURES: Food
insecurity was measured when children were aged 9 months (wave 1), 2 years (wave
2), and 4 years (wave 3). Parental history of disruptive life events was measured
at wave 1. ANALYSIS: Logistic regression was used to carry out the analyses.
RESULTS: Each examined disruptive life event was associated with a significant
increase in the odds of persistent household food insecurity (P < .05). The
probability of persistent household food insecurity was >6 times as large in
households with 1 or both parents reporting the occurrence of each of the
disruptive life events, relative to households with none of these parental risk
factors. CONCLUSIONS AND IMPLICATIONS: Practitioners may want to consider
parental history of various disruptive life events in their assessment of
familial risk of household food insecurity. Future policy efforts might include a
cost-benefit estimate analysis of intervening earlier in the food insecurity
disruptive life events nexus to advocate for savings to the taxpayer for
prevention services. Moreover, future research could evaluate these practice and
policy-driven efforts using quasi-experimental designs.
PMID- 28689610
TI - Characteristics of Americans Choosing Vegetarian and Vegan Diets for Health
Reasons.
AB - OBJECTIVE: Examine the prevalence, patterns, and associated factors of using a
vegetarian or vegan diet for health reasons in the US general population. DESIGN:
Cross-sectional data from the 2012 National Health Interview Survey.
PARTICIPANTS: Nationally representative sample (N = 34,525). VARIABLES MEASURED:
Prevalence of ever use and 12-month use of vegetarian or vegan diet for health
reasons, patterns of use, and sociodemographic and health-related factor
associated with use. ANALYSIS: Multiple logistic regression analysis. RESULTS:
Prevalence of ever use and 12-month use was 4.0% (n = 1,367) and 1.9% (n = 648),
respectively. Health vegetarians and vegans were more likely aged 30-65 years,
female, not Hispanic, from the Western US region, at least high school educated,
chronically ill, and physically active. They were less likely to be in a
relationship, overweight or obese, or smoking, or to have public or private
health insurance. Among health vegetarians and vegans, 6.3% consulted with a
practitioner for special diets; 26.1% followed the diet because of a specific
health problem, mainly high cholesterol, overweight, hypertension, and diabetes;
and 59.4% disclosed the diet to their health care provider. CONCLUSIONS AND
IMPLICATIONS: Less than 2% of participants reported using a vegetarian or vegan
diet for health reasons within the past 12 months. Despite potential benefits of
plant-based nutrition, more research is warranted on the actual use and its
effects and safety.
PMID- 28689611
TI - A Qualitative Application of the Belsky Model to Explore Early Care and Education
Teachers' Mealtime History, Beliefs, and Interactions.
AB - OBJECTIVE: Studies on factors associated with nutrition practices in early care
and education settings often focus on sociodemographic and programmatic
characteristics. This qualitative study adapted and applied Belsky's determinants
of parenting model to inform a broader exploration of Early Care and Education
Teachers (ECETs) practices. DESIGN: Qualitative cross-sectional study with ECETs.
SETTING: The researchers interviewed ECETs in their communities across a Southern
state. PARTICIPANTS: Purposive sampling was employed to recruit ECETs (n = 28)
from Head Start or state-funded centers serving low-income families. PHENOMENON
OF INTEREST: Developmental histories of ECETs regarding food and nutrition,
beliefs about child nutrition, and teaching interactions related to food.
ANALYSIS: Qualitative interviews were coded using a deductive content analysis
approach. RESULTS: Three distinct interrelationships were observed across the
themes. First, rules and routines regarding food and mealtime in the educators'
childhood often aligned with educator beliefs and behaviors at meals in their
classroom. Second, some ECETs described motivations to leave a healthy food
legacy for children in their class. Finally, an experience of food insecurity
appeared in narratives that also emphasized making sure children got enough
through various strategies. CONCLUSIONS AND IMPLICATIONS: The influence of ECET
developmental histories and their related beliefs can be addressed through
professional development and ongoing support. Future study should quantify model
constructs in a larger sample and study their relationships over time.
PMID- 28689612
TI - Observations and Conversations: Home Preparation of Infant Formula Among a Sample
of Low-Income Mothers in the Southeastern US.
AB - OBJECTIVE: Explore infant formula preparation attitudes and beliefs among low
income, formula-feeding, Southeastern US mothers. DESIGN: Cross-sectional study
using in-home observations and in-depth interviews. SETTING: Participant homes.
PARTICIPANTS: Thirteen low-income mothers of normal birth weight, healthy, term
infants aged <=3 months, who were predominantly feeding powdered or from
concentrate formula. VARIABLES MEASURED: Reading formula preparation
instructions; order of added ingredients; leveling powdered formula scoop(s);
adding cereal or other ingredients to bottles. PHENOMENON OF INTEREST:
Perceptions of formula preparation or manipulation. ANALYSIS: Descriptive
statistics described sample characteristics and home observation variables.
Thematic analysis of in-depth interviews revealed the following major themes:
formula preparation can be intimidating; expressions of complex heuristic
perceptions about formula preparation; cost and convenience motivate maternal
behaviors; and infant cues override recommendations. Data from qualitative and
quantitative activities were triangulated. RESULTS: Behaviors, including improper
reconstitution and modifications/additions to prepared formula (eg, infant
cereal) were observed during home observations and/or described during in-depth
interviews. Inconsistencies were detected between observed behaviors (eg, adding
too much water to the bottle) and those reported during in-depth interviews (eg,
stating over-dilution could be detrimental to the infant's health). CONCLUSIONS
AND IMPLICATIONS: Targeting knowledge or skills gaps and behavioral motivators in
the formula-feeding population could positively affect infant-feeding practices
that occur outside of recommendations.
PMID- 28689613
TI - Evaluation of Factorial Validity and Reliability of a Food Behavior Checklist for
Low-Income Filipinos.
AB - OBJECTIVE: To examine factorial validity, test-retest reliability, and internal
consistency of a Tagalog-language food behavior checklist (FBC) for a low-income
Filipino population. METHODS: Participants (n = 160) completed the FBC on 2
occasions 3 weeks apart. Factor structure was examined using principal component
analysis. For internal consistency, Cronbach alpha was calculated. For test
retest reliability, Spearman correlation or intraclass correlation coefficient
(ICC) was calculated between scores at the 2 points. RESULTS: All but 1 item
loaded on 6 factors: fruit and vegetable quantity, fruit and vegetable variety,
fast food, sweetened beverage, healthy fat, and diet quality. Cronbach alpha was
.75 for the total scale (range, .39-.76 for subscales). Spearman correlation was
0.78 (ICC, 0.79) for the total scale (range, 0.66-0.80 [ICC, 0.68-0.80] for
subscales). CONCLUSIONS AND IMPLICATIONS: The FBC demonstrated adequate factorial
validity, test-retest reliability, and internal consistency. With additional
testing, the FBC may be used to evaluate the US Department of Agriculture's
nutrition education programs for Tagalog speakers.
PMID- 28689614
TI - Smart Snacks in School Legislation Does Not Change Self-Reported Snack Food and
Beverage Intake of Middle School Students in Rural Appalachian Region.
AB - OBJECTIVE: To assess the effects of the national Smart Snacks in School
standards, which include nutrient and ingredient limitations for school
competitive foods and beverages effective July, 2014, on student intake in low
income rural Appalachian middle schools. METHODS: Food-frequency questionnaires
were administered to students before and after implementation. Multiple ordinal
logistic regression models were conducted to examine effects from year of data
collection, grade, and free or reduced price lunch participation rates. RESULTS:
No significant changes were observed after implementation except a decrease in
consumption of 1% or nonfat flavored milk at school. CONCLUSIONS AND
IMPLICATIONS: Smart Snacks in School standards did not result in significant
dietary changes in this study. Longitudinal studies could evaluate long-term
impacts of nutrition standards.
PMID- 28689615
TI - Weight Bias Education for Medical School Faculty: Workshop and Assessment.
PMID- 28689616
TI - Body Quest: Food of the Warrior.
PMID- 28689617
TI - Response to Body Quest: Food of the Warrior.
PMID- 28689618
TI - Erratum.
PMID- 28689619
TI - Two cases of granulomatosis polyangiitis presenting with Strawberry gingivitis
and a review of the literature.
AB - Hyperplastic gingivitis is a rare manifestation of granulomatosis with
polyangiitis (GPA). This gingivitis has a very distinctive clinical appearance
(so-called Strawberry gingivitis) and when seen is virtually pathognomic for GPA.
Gingivitis often precedes other organ involvement therefore making awareness of
this manifestation particularly important to aid early diagnosis and treatment.
Furthermore, histopathological findings of gingival specimens rarely reveal
necrotizing granulomatous vasculitis, which is classically seen at other sites of
involvement. As a result a delay in diagnosis is not uncommon. GPA if left
untreated has a high mortality rate and early immunosuppressive treatment is
associated with an improved prognosis. We present two cases of patients with GPA
presenting with characteristic strawberry gingivitis and review the reported
cases.
PMID- 28689620
TI - Enhancing communication in obstetric anaesthesia - listen, listen, listen....
PMID- 28689621
TI - Intrathecal hematoma and arachnoiditis mimicking bacterial meningitis after an
epidural blood patch.
AB - We present a case of arachnoiditis and an intrathecal hematoma after an epidural
blood patch. A 24-year-old parturient underwent an epidural blood patch three
days after an accidental dural puncture during epidural labor analgesia. Four
days later, the patient developed severe lower back pain, bilateral leg pain,
persistent headache and fever. Bacterial meningitis was initially suspected and
antibiotics started. Lumbar magnetic resonance imaging was performed and showed
an intrathecal hematoma, with no blood in the epidural space. This report briefly
reviews the few cases in the literature of arachnoiditis caused by an intrathecal
hematoma and discusses the mechanism which resulted in blood in the subarachnoid
space.
PMID- 28689622
TI - The role of carbetocin in the prevention and management of postpartum
haemorrhage.
PMID- 28689623
TI - The role of carbetocin in the prevention and management of postpartum haemorrhage
- In reply.
PMID- 28689624
TI - Neonatal effects after vasopressor during spinal anesthesia for cesarean section:
a multicenter, randomized controlled trial.
AB - BACKGROUND: Placental transfer of ephedrine causes fetal effects when compared
with phenylephrine. This study compared their drug effects on neonatal parameters
after cesarean delivery under spinal anesthesia. METHODS: Three-hundred-and-fifty
four women undergoing elective cesarean delivery who needed intravenous
vasopressor following spinal anesthesia were randomized into two groups. Group E
received boluses of ephedrine 6mg, and Group P phenylephrine 100ug, titrated to
maintain systolic blood pressure near baseline values. Neonatal heart rates at 10
and 30-45min of age, oxygen saturation and capillary blood glucose at 30min, and
capillary blood lactate and urine metamphetamine were recorded. RESULTS: Neonatal
heart rate at 10min was significantly higher (mean difference 4.0, 95%CI 0.6 to
7.3, P=0.02) in Group E versus Group P, but this was not clinically relevant.
There was a linear correlation between neonatal heart rate at 10min and ephedrine
dose in Group E (r2=0.29, 95%CI 0.22, 0.74, p<0.01). The decremental changes in
neonatal heart rate at 10 and 30min were significantly greater in Group E. Urine
metamphetamine tests were positive in 19% of 44 neonatal urine samples. Neonatal
heart rates at 30min, oxygen saturation, capillary blood glucose and the
incidence of tachycardia, respiratory problems or abnormal glucose, were not
significantly different. CONCLUSIONS: Ephedrine, compared to phenylephrine as a
vasopressor during cesarean delivery, was associated with higher neonatal heart
rate in the early post-birth period, but without a significant difference in
clinical outcomes in uncomplicated pregnancies.
PMID- 28689625
TI - The preventive approach: OPCAT and the prevention of violence and abuse of
persons with mental disabilities by monitoring places of detention.
AB - Adopted in December 2002, the United Nations Optional Protocol to the Convention
against Torture and other Cruel, Inhuman or Degrading Treatment or Punishment
establishes a system of regular visits undertaken by independent international
and national bodies to places where people are deprived of their liberty, in
order to prevent torture and other cruel, inhuman or degrading treatment or
punishment. The article explores how this collaboration between national and
international bodies, with independent mandates to carry out such unannounced
visits, represents an important effort in the process of protecting persons with
mental disabilities who are detained and who are particularly exposed to
exploitation and other forms of serious human rights violations, contrary to
Article 16 of the Convention on the Rights of Persons with Disabilities.
PMID- 28689626
TI - Violence and abuse against people with disabilities: A comparison of the
approaches of the European Court of Human Rights and the United Nations Committee
on the Rights of Persons with Disabilities.
AB - This paper explores how, and how effectively, two systems of international law
have addressed exploitation, violence and abuse of people with mental
disabilities. The two international systems reviewed were the Council of Europe's
European Court of Human Rights and the United Nations Committee on the Rights of
Persons with Disabilities. The two issues dealt with are (a) forced
institutionalisation and denial of community-based services and (b) medically
sanctioned treatment as abuse or violence. The paper offers a comparative
analysis of the way in which the two bodies have dealt with exploitation,
violence and abuse of people with disabilities, and offers recommendations as to
how the two bodies could adjust their approaches to come into closer alignment.
PMID- 28689627
TI - Promises of protection? Article 16 of the Convention on the Rights of Persons
with Disabilities and gender-based violence in South Africa.
AB - Article 16 of the Convention on the Rights of Persons with Disabilities (CRPD)
guarantees persons with disabilities freedom from exploitation, violence and
abuse. This article explores the current status of implementation of article 16
in South Africa, with specific reference to the legislative framework
underpinning protection from exploitation, violence and abuse. This investigation
is done specifically in the context of gender-based violence, which remains a
cause of great concern in this country.
PMID- 28689628
TI - Preventing violence, exploitation and abuse of persons with mental disabilities:
Exploring the monitoring implications of Article 16 of the United Nations
Convention on the Rights of Persons with Disabilities.
AB - Article 16 of the United Nations Convention on the Rights of Persons with
Disabilities includes the right to be free from all forms of violence,
exploitation and abuse. In pursuance of this aim, Article 16 (3) imposes an
obligation on States Parties to 'ensure that all facilities and programmes
designed to serve persons with disabilities are effectively monitored by
independent authorities'. Effective independent monitoring is viewed as a key
mechanism to help safeguard people from violence, exploitation and abuse. This is
highly pertinent in the wake of the highly publicized abuse of patients in care
homes and hospitals in England in the last few years. This article examines the
monitoring requirements of Article 16 and, by drawing on the author's research
into the Care Quality Commission (the national health and social care regulator
and mental health monitor) in England, assesses the extent to which independent
inspection of hospitals and care homes can play a part in realizing Article 16(3)
to prevent violence, abuse and exploitation of persons with mental disabilities.
The potential scope and reach of Article 16 is extremely wide: this brings with
it great potential but, at the same time, significant challenges for achieving
effecting monitoring. Some of these challenges are explored and the paper
concludes with some consideration of how monitors/inspectors, such as the Care
Quality Commission in England, can strengthen their protection for people with
mental disabilities, in line with the ethos and aspirations of the CRPD.
PMID- 28689629
TI - The challenges of GxE: Commentary on "Genetic Endowments, parental resources and
adult health: Evidence from the Young Finns Study".
PMID- 28689630
TI - Using a structural competency framework to teach structural racism in pre-health
education.
AB - The inclusion of structural competency training in pre-health undergraduate
programs may offer significant benefits to future healthcare professionals. This
paper presents the results of a comparative study of an interdisciplinary pre
health curriculum based in structural competency with a traditional premedical
curriculum. The authors describe the interdisciplinary pre-health curriculum,
titled Medicine, Health, and Society (MHS) at Vanderbilt University. The authors
then use a new survey tool, the Structural Foundations of Health Survey, to
evaluate structural skills and sensibilities. The analysis compares MHS majors (n
= 185) with premed science majors (n = 63) and first-semester freshmen (n = 91),
with particular attention to understanding how structural factors shape health.
Research was conducted from August 2015 to December 2016. Results suggest that
MHS majors identified and analyzed relationships between structural factors and
health outcomes at higher rates and in deeper ways than did premed science majors
and freshmen, and also demonstrated higher understanding of structural and
implicit racism and health disparities. The skills that MHS students exhibited
represent proficiencies increasingly stressed by the MCAT, the AAMC, and other
educational bodies that emphasize how contextual factors shape expressions of
health and illness.
PMID- 28689631
TI - Vasculogenic mimicry in vitro in tumour cells derived from metastatic malignant
pleural effusions.
PMID- 28689632
TI - Foreign body ileitis: a histopathological mimic of Crohn's disease?
PMID- 28689633
TI - Follicular lymphoma with hyaline-vascular Castleman disease-like follicles and
CD20 positive follicular dendritic cells.
PMID- 28689635
TI - Extrauterine peritoneal placental site nodule.
PMID- 28689634
TI - Impact of the Australian gender specific thresholds using the Abbott high
sensitivity troponin I assay in clinical care.
AB - The aim of this study was to ascertain the impact of gender specific hs-TnI
thresholds in a clinical setting and determine the clinical characteristics and
discharge diagnosis for individuals presenting to the Emergency Department (ED)
with elevated troponin I with the Abbott high-sensitivity troponin I (hs-TnI)
assay, but non-elevated troponin I on the previous generation assay (STAT TnI
II). Medical records of individuals presenting to the Royal Perth Hospital ED
with elevated hs-TnI between 12 November 2013 and 24 December 2013 were
retrospectively reviewed. The 99th percentile hs-TnI thresholds were >=26 ng/L
for males and >=16 ng/L for females. TnI-II assays were performed concomitantly.
In total, 1449 individuals [855 (59%) males] had 3580 troponin measurements. hs
TnI was elevated in 1569 (43.8%) measurements. Elevated hs-TnI with normal TnI-II
was found in 120 (8.3%) individuals: 77 (64%) females and 43 (36%) males. Eight
(6.7%) individuals were diagnosed with acute coronary syndrome (ACS): four (9.3%)
males and four (5.2%) females. Other cardiac aetiologies were found in 33 (42%)
females and 17 (40%) males. Individuals with elevated hs-TnI had high rates of
hypertension (80%), diabetes mellitus (33%), cardiac failure (23%), aspirin use
(53%) and lipid lowering therapy (52%). Significantly fewer females than males
with discrepant troponin I results had previous ischaemic heart disease. The
hsTnI assay identifies 8% more individuals with elevated troponin in an acute
setting, with a female predominance (64%). However, only 6.7% of these
individuals with multiple cardiovascular risk factors were diagnosed with ACS, a
~0.5% increase overall. Outcome studies are required to determine if the
Australian hs-TnI thresholds are clinically appropriate.
PMID- 28689636
TI - Dynamic transcription and expression patterns of KIF3A and KIF3B genes during
spermiogenesis in the shrimp, Palaemon carincauda.
AB - Spermiogenesis is a highly ordered and complex process in the male germ cell
differentiation. The microtubule-based motor proteins KIF3A and KIF3B are
required for the progression of the stages of spermiogenesis. In this study, the
main goal was to determine whether KIF3A and KIF3B have a key role in
spermiogenesis in Palaemon carincauda. The complete cDNA of KIF3A/3B from the
testis of P. carincauda was cloned by using PCR and rapid amplification of cDNA
ends (RACE). The predicted secondary and tertiary structures of KIF3A/3B
contained three domains which were the: a) head region, b) stalk region, and c)
tail region. Real-time quantitative PCR (qPCR) results revealed that KIF3A and
KIF3B mRNAs were obtained for all the tissues examined, with the greatest gene
expression in the testis. In situ hybridization indicated the KIF3A and KIF3B
mRNAs were distributed in the periphery of the nuclear in the early spermatid of
spermiogenesis. In the middle and late spermatid stages, KIF3A and KIF3B mRNAs
were gradually upregulated and assembled to one side where acrosome biogenesis
begins. In the mature sperm, KIF3A and KIF3B mRNAs were distributed in the
acrosome cap and spike. Immunofluorescence studies indicated that KIF3A, tubulin,
mitochondria, and Golgi were co-localized in different stages during
spermiogenesis in P. carincauda. The temporal and spatial gene expression
dynamics of KIF3A/3B indicate that KIF3A and KIF3B proteins may be involved in
acrosome formation and nucleus shaping. Moreover, these proteins can transport
the mitochondria and Golgi that facilitate acrosome formation in P. carincauda.
PMID- 28689637
TI - Measurement of flow of thought in 68 patients monitored in post-emergency
outpatient consultations: Role of ideational turmoil in the anxiety depressive
symptomatology.
AB - INTRODUCTION: Rumination, cognitive control deficits, cognitive saturation, and
loss of inhibition are the major hypotheses used to explain depressive disorders.
A few studies have nevertheless looked at the form of thought. In this study, we
will test a double measurement of the number of thoughts and a double measurement
of the flow of thought together with their correlation with well-being, mental
pain, and depression. MATERIAL AND METHODS: Between May and September 2015, 68
subjects, initially admitted as emergencies for acute anxiety depressive
disorders and/or suicide attempts and subsequently monitored as post-emergency
outpatients in medico-psychological consultations agreed to complete a set of
Visual Analogue Scales measuring their well-being, their mental pain, their
estimated number of thoughts and the how agitated these thoughts are estimated to
be. A double evaluation of the cognitive activity consisted of representation
intrusive thoughts by filling a drawing of an aquarium to reflect the number of
thoughts (by drawing fish) and cognitive turmoil (by drawing wavy lines). The
depressive illness was evaluated using the Beck depression inventory and by rater
administered assessments using MADRS (Montgomery-Asberg Depression Scale).
RESULTS: These measurements are of good psychometric quality (sensitivity,
accuracy, validity). The mental pain is related to mental turmoil. These results
reveal positive correlations between the mental turmoil and the total score on
the depression. The use of the aquarium makes it possible to distinguish the
feeling of having "a lot of thoughts" from the feeling of having "agitated
thoughts". So, the total score of wavy lines shows positive correlation with the
total score on the depression inventory (BDI) and the total MADRS score.
DISCUSSION: The results suggest that the phenomena of cognitive saturation and
the sensation of mental restlessness play a major role in the etiopathogensis of
depression. The analyses show that the cognitive dysregulation is situated more
precisely at the level of the flow of thought rather than the level of the number
of thoughts. A deterioration in the flow of thought increases the mental pain and
the depressive symptoms, and reduces well-being. The sample is nevertheless
small, and some bias appears in the filling of the aquarium boxes.
PMID- 28689638
TI - [OISO, automatic treatment of patients management in oncogenetics].
AB - INTRODUCTION: Oncogenetics is a long-term process, which requires a close
relation between patients and medical teams, good familial links allowing
lifetime follow-up. Numerous documents are exchanged in between the medical team,
which has to frequently interact. We present here a new tool that has been
conceived specifically for this management. METHODS: The tool has been developed
according to a model-view-controler approach with the relational system
PostgreSQL 9.3. The web site used PHP 5.3, HTML5 and CSS3 languages, completed
with JavaScript and jQuery-AJAX functions and two additional modules, FPDF and
PHPMailer. RESULTS: The tool allows multiple interactions, clinical data
management, mailing and emailing, follow-up plannings. Requests are able to
follow all patients and planning automatically, to send information to a large
number of patients or physicians, and to report activity. DISCUSSION: The tool
has been designed for oncogenetics and adapted to its different aspects. The CNIL
delivered an authorization for use. Secured web access allows the management at a
regional level. Its simple concept makes it evolutive according to the constant
updates of genetic and clinical management of patients.
PMID- 28689640
TI - Distinct Ventral Pallidal Neural Populations Mediate Separate Symptoms of
Depression.
AB - Major depressive disorder (MDD) patients display a common but often variable set
of symptoms making successful, sustained treatment difficult to achieve. Separate
depressive symptoms may be encoded by differential changes in distinct circuits
in the brain, yet how discrete circuits underlie behavioral subsets of depression
and how they adapt in response to stress has not been addressed. We identify two
discrete circuits of parvalbumin-positive (PV) neurons in the ventral pallidum
(VP) projecting to either the lateral habenula or ventral tegmental area
contributing to depression. We find that these populations undergo different
electrophysiological adaptations in response to social defeat stress, which are
normalized by antidepressant treatment. Furthermore, manipulation of each
population mediates either social withdrawal or behavioral despair, but not both.
We propose that distinct components of the VP PV circuit can subserve related,
yet separate depressive-like phenotypes in mice, which could ultimately provide a
platform for symptom-specific treatments of depression.
PMID- 28689639
TI - Regulation of inflammation by members of the formyl-peptide receptor family.
AB - Inflammation is associated with a variety of diseases. The hallmark of
inflammation is leukocyte infiltration at disease sites in response to pathogen-
or damage-associated chemotactic molecular patterns (PAMPs and MAMPs), which are
recognized by a superfamily of seven transmembrane, Gi-protein-coupled receptors
(GPCRs) on cell surface. Chemotactic GPCRs are composed of two major subfamilies:
the classical GPCRs and chemokine GPCRs. Formyl-peptide receptors (FPRs) belong
to the classical chemotactic GPCR subfamily with unique properties that are
increasingly appreciated for their expression on diverse host cell types and the
capacity to interact with a plethora of chemotactic PAMPs and MAMPs. Three FPRs
have been identified in human: FPR1-FPR3, with putative corresponding mouse
counterparts. FPR expression was initially described in myeloid cells but
subsequently in many non-hematopoietic cells including cancer cells. Accumulating
evidence demonstrates that FPRs possess multiple functions in addition to
controlling inflammation, and participate in the processes of many
pathophysiologic conditions. They are not only critical mediators of myeloid cell
trafficking, but are also implicated in tissue repair, angiogenesis and
protection against inflammation-associated tumorigenesis. A series recent
discoveries have greatly expanded the scope of FPRs in host defense which
uncovered the essential participation of FPRs in step-wise trafficking of myeloid
cells including neutrophils and dendritic cells (DCs) in host responses to
bacterial infection, tissue injury and wound healing. Also of great interest is
the FPRs are exploited by malignant cancer cells for their growth, invasion and
metastasis. In this article, we review the current understanding of FPRs
concerning their expression in a vast array of cell types, their involvement in
guiding leukocyte trafficking in pathophysiological conditions, and their
capacity to promote the differentiation of immune cells, their participation in
tumor-associated inflammation and cancer progression. The close association of
FPRs with human diseases and cancer indicates their potential as targets for the
development of therapeutics.
PMID- 28689641
TI - Life-Long Genetic and Functional Access to Neural Circuits Using Self
Inactivating Rabies Virus.
AB - Neural networks are emerging as the fundamental computational unit of the brain
and it is becoming progressively clearer that network dysfunction is at the core
of a number of psychiatric and neurodegenerative disorders. Yet, our ability to
target specific networks for functional or genetic manipulations remains limited.
Monosynaptically restricted rabies virus facilitates the anatomical investigation
of neural circuits. However, the inherent cytotoxicity of the rabies largely
prevents its implementation in long-term functional studies and the genetic
manipulation of neural networks. To overcome this limitation, we developed a self
inactivating DeltaG-rabies virus (SiR) that transcriptionally disappears from the
infected neurons while leaving permanent genetic access to the traced network.
SiR provides a virtually unlimited temporal window for the study of network
dynamics and for the genetic and functional manipulation of neural circuits in
vivo without adverse effects on neuronal physiology and circuit function.
PMID- 28689642
TI - Cells in 3D-reconstitutued eccrine sweat gland cell spheroids differentiate into
gross cystic disease fluid protein 15-expressing dark secretory cells and
carbonic anhydrase II-expressing clear secretory cells.
AB - Secretory coils of eccrine sweat glands are composed of myoepithelial cells, dark
secretory cells and clear secretory cells. The two types of cells play important
roles in sweat secretion. In our previous study, we demonstrated that the 3D
reconstituted eccrine sweat gland cell spheroids differentiate into secretory
coil-like structures. However, whether the secretory coil-like structures further
differentiate into dark secretory cells and clear secretory cells were is still
unknown. In this study, we detected the differentiation of clear and dark
secretory cells in the 3D-reconstituted eccrine sweat gland cell spheroids using
the dark secretory cell-specific marker, GCDFP-15, and clear secretory cell
specific marker, CAII by immunofluorescence staining. Results showed that there
were both GCDFP-15- and CAII-expressing cells in 12-week-old 3D spheroids,
similar to native eccrine sweat glands, indicating that the spheroids possess a
cellular structure capable of sweat secretion. We conclude that the 12-week 3D
spheroids may have secretory capability.
PMID- 28689643
TI - Suicide Means among Decedents Aged 50+ Years, 2005-2014: Trends and Associations
with Sociodemographic and Precipitating Factors.
AB - OBJECTIVE: To examine 1) temporal trends between 2005 and 2014 in the three most
frequently used suicide means (firearms, hanging/suffocation,
alcohol/drug/medicine overdose) by decedents aged 50+ years and 2) associations
of suicide means with sociodemographic and precipitating factors. METHODS: The
National Violent Death Reporting System, 2005-2014, provided data (N = 46,857).
Suicide means were identified from ICD-10 codes for underlying cause of death and
coroner/medical examiner (CME) reports. Precipitating factors are based on either
CME or law enforcement report. Age-group (50-64 and 65+ years) and gender
separate logistic regression analyses were used to examine study questions.
RESULTS: In the 50-64 years age group, each advancing year (i.e., from 2005 to
2014) was associated with a 1% decrease in the odds of firearm use and a 6%
increase in the odds of hanging/suffocation among men; a 9% increase in the odds
of hanging/suffocation among women; and a 4% decrease in the odds of overdose
among each gender. In the 65+ years age group, each advancing year was associated
with a 4% increase in the odds of overdose among men. Physical health was a
significant factor for firearm use among men (adjusted odds ratio: 1.47; 95% CI:
1.39-1.55) only. Regardless of gender and age, mental health and substance abuse
problems and prior suicide attempts were associated with hanging/suffocation and
overdose. CONCLUSIONS: Firearm use decreased among men aged 50-64 years between
2005 and 2014, but its use did not change among the other gender by age groups.
With rapidly growing numbers of older adults, routine suicide risk assessments,
firearm safety monitoring, and interventions to improve quality of life are
needed.
PMID- 28689644
TI - Childhood Stress and Adversity is Associated with Late-Life Dementia in
Aboriginal Australians.
AB - OBJECTIVES: High rates of dementia have been observed in Aboriginal Australians.
This study aimed to describe childhood stress in older Aboriginal Australians and
to examine associations with late-life health and dementia. DESIGN: A cross
sectional study with a representative sample of community-dwelling older
Aboriginal Australians. SETTING: Urban and regional communities in New South
Wales, Australia. PARTICIPANTS: 336 Aboriginal and/or Torres Strait Islander
Australians aged 60-92 years, of whom 296 were included in the current analyses.
MEASUREMENTS: Participants completed a life course survey of health, well-being,
cognition, and social history including the Childhood Trauma Questionnaire (CTQ),
with consensus diagnosis of dementia and Alzheimer disease. RESULTS: CTQ scores
ranged from 25-117 (median: 29) and were associated with several adverse
childhood indicators including separation from family, poor childhood health,
frequent relocation, and growing up in a major city. Controlling for age, higher
CTQ scores were associated with depression, anxiety, suicide attempt, dementia
diagnosis, and, specifically, Alzheimer disease. The association between CTQ
scores and dementia remained significant after controlling for depression and
anxiety variables (OR: 1.61, 95% CI: 1.05-2.45). In contrast, there were no
significant associations between CTQ scores and smoking, alcohol abuse, diabetes,
or cardiovascular risk factors. CONCLUSIONS: Childhood stress appears to have a
significant impact on emotional health and dementia for older Aboriginal
Australians. The ongoing effects of childhood stress need to be recognized as
people grow older, particularly in terms of dementia prevention and care, as well
as in populations with greater exposure to childhood adversity, such as
Aboriginal Australians.
PMID- 28689646
TI - Higher M30 and high mobility group box 1 protein levels in ex vivo lung perfusate
are associated with primary graft dysfunction after human lung transplantation.
AB - BACKGROUND: Ex vivo lung perfusion (EVLP) enables assessment of marginal donor
lungs for transplantation, with similar clinical outcomes to conventional lung
transplantation. We investigated whether cell death-related proteins in the EVLP
perfusate could predict primary graft dysfunction (PGD) after transplantation.
METHODS: M30 (indicating epithelial apoptosis), M65 (indicating total epithelial
cell death), and high mobility group box 1 (HMGB-1, related to cell death and
inflammation) protein levels in EVLP perfusate were measured by enzyme-linked
immunosorbent assay and correlated with clinical outcomes. RESULTS: From 100
sequential EVLP patients, 79 lungs were transplanted. Patients who were bridged
with extracorporeal life support (ECLS, n = 6) or who received lobar/single lung
(n = 25) were excluded. PGD grade 3 (partial pressure of arterial oxygen/fraction
of inspired oxygen <200 or need for ECLS) developed in 11 at any time within 72
hours after transplantation (PGD Group). PGD grade 3 did not develop in 34
patients (Control Group). M30 was significantly higher in the PGD Group than in
the Control Group at 1 hour (PGD: 73.3 +/- 24.9, control: 53.9 +/- 15.9 U/liter;
p < 0.01) and at 4 hours (PGD: 137.0 +/- 146.6, Control: 72.4 +/- 40.0 U/liter; p
= 0.046) of EVLP. The increase of HMGB-1 from 1 to 4 hours of EVLP was
significantly greater in the PGD Group (PGD: 37.0 +/- 25.4, Control: 7.2 +/- 16.8
ng/ml; p < 0.001). Higher levels of or a greater increase in M30 and a greater
increase in HMGB-1 were associated with higher mortality in Cox regression.
CONCLUSIONS: Levels of M30 and HMGB-1 in the EVLP perfusate correlate with PGD
after lung transplantation and might therefore be useful biomarkers to improve
donor lung assessment during EVLP.
PMID- 28689647
TI - Effectiveness of a physical activity programme based on the Pilates method in
pregnancy and labour.
AB - OBJECTIVE: To assess the effectiveness and safety of a physical activity
programme based on use of the Pilates method, over eight weeks in pregnant women,
on functional parameters, such as weight, blood pressure, strength, flexibility
and spinal curvature, and on labour parameters, such as, type of delivery,
episiotomy, analgesia and newborn weight. METHOD: A randomized clinical trial was
carried out on pregnant women, applying a programme of physical activity using
the Pilates method, designed specifically for this population. A sample
consisting of a total of 105 pregnant women was divided into two groups:
intervention group (n=50) (32.87+/-4.46 years old) and control group (n=55)
(31.52+/-4.95 years old). The intervention group followed a physical activity
programme based on the Pilates method, for 2 weekly sessions, whereas the control
group did not follow the program. RESULTS: Significant improvements (p<0.05) in
blood pressure, hand grip strength, hamstring flexibility and spinal curvature,
in addition to improvements during labour, decreasing the number of Caesareans
and obstructed labour, episiotomies, analgesia and the weight of the newborns
were found at the end of the intervention. CONCLUSION: A physical activity
programme of 8 weeks based on the Pilates method improves functional parameters
in pregnant women and benefits delivery.
PMID- 28689645
TI - Additive Role of a Potentially Reversible Cognitive Frailty Model and
Inflammatory State on the Risk of Disability: The Italian Longitudinal Study on
Aging.
AB - OBJECTIVE: Cognitive frailty is a condition recently defined by operationalized
criteria describing the simultaneous presence of physical frailty and mild
cognitive impairment (MCI). Two subtypes for this clinical construct have been
proposed: "potentially reversible" cognitive frailty (physical frailty plus MCI)
and "reversible" cognitive frailty (physical frailty plus pre-MCI subjective
cognitive decline). Here the prevalence of a potentially reversible cognitive
frailty model was estimated. It was also evaluated if introducing a diagnosis of
MCI in older subjects with physical frailty could have an additive role on the
risk of dementia, disability, and all-cause mortality in comparison with frailty
state or MCI condition alone, with analyses separately performed for inflammatory
state. METHODS: In 2,373 individuals from the population-based Italian
Longitudinal Study on Aging with a 3.5-year-follow-up, we operationally
categorized older individuals without dementia into four groups: non-frail/non
MCI, non-frail/MCI, frail/non-MCI, and frail/MCI. RESULTS: The prevalence of
potentially reversible cognitive frailty was 1%, increasing with age and more
represented in women than in men, and all groups were associated with significant
increased incident rate ratios of dementia, disability, and mortality. A
significant difference in rates of disability has been found between the MCI and
non-MCI groups (contrasts of adjusted predictions: 0.461; 95% confidence
interval: 0.187-0.735) in frail individuals with high inflammatory states
(fibrinogen >339 mg/dL). CONCLUSION: In older individuals without dementia and
with elevated inflammation, a potentially reversible cognitive frailty model
could have a significant additional predictive effect on the risk of disability
than the single conditions of frailty or MCI.
PMID- 28689648
TI - Clinical and genetic characterization of Chinese pediatric cystine stone
patients.
AB - INTRODUCTION: Cystine stone is the only clinical manifestation in patients with
cystinuria, which is an autosomal recessive inheritable disease. However,
clinical and genetic data vary among patients in different countries. OBJECTIVE:
To investigate the characteristics of Chinese pediatric cystine stone patients.
PATIENTS AND METHODS: Thirteen pediatric patients with cystine stones were
evaluated in our clinic between 2012 and 2015. Gene mutations in SLC3A1 and
SLC7A9 were investigated. Metabolic evaluation was also performed. Thirteen
pediatric patients with calcium oxalate stones were selected as controls.
RESULTS: Of these patients, eight were males and five were females. Average age
at detection of the first stone was 6.8 +/- 5.2 years. Urinary stones in three of
the 13 cystine patients were composed of cystine and calcium oxalate. The 63.6%
of patients with upper urinary stones had bilateral stones. A total of 17
different missense mutations were identified, and 12 of these mutations were
first reported in this study. Metabolic abnormalities could be detected in 77% of
cystine stone patients. The most common metabolic abnormality was hyperoxaluria,
followed by hypercalciuria and hypocitraturia. Compared with calcium stone
patients, our cystine stone patients had a higher rate of bilateral stones,
larger stone size, higher levels of serum BUN and Cr, urine citrate excretion
(Table), and higher mean value of surgeries per patient. By contrast, the
opposite was true for urine oxalate excretion and AP (CaOx) index EQ. The urine
excretion of cystine was not correlated with other urinary constituents.
DISCUSSION: Patients with cystinuria frequently suffer recurrent renal stones and
may subsequently need a series of stone removal procedures during their lifetime.
This condition is likely to affect their overall renal function. SLC3A1 and
SLC7A9 have been extensively investigated, but a detection rate of 100% in
cystinuric patients has yet to be obtained. In our study, we found 14 missense
mutations in 18 of 26 alleles except four mutation polymorphisms. Most of the
gene mutations found in our study were their first reports. Metabolic
abnormalities were frequently found in cystine stone patients, but their risk of
calcium oxalate stone formation was relatively lower than that of patients with
calcium oxalate stones. CONCLUSIONS: Cystine stone patients are at risk of
impaired renal function and the formation of calcium oxalate stones. Most of the
gene mutations identified in our patients were first reported in this study.
Therefore, cystinuria possibly exhibits genetic and allelic heterogeneity in
Chinese pediatric cystine stone patients.
PMID- 28689649
TI - Epispadias repair with tunica vaginalis flap.
AB - INTRODUCTION: Primary epispadias is a rare congenital malformation that afflicts
about 1 in 80,000 children. The surgical repair, originally described by Cantwell
over 100 years ago, is fundamentally sound and incorporates several important
steps to achieve an optimal result. METHODS: A 9-month-old male with penopubic
epispadias presented for surgical repair. Pre-operative imaging included a normal
renal ultrasound and voiding cystourethrogram that demonstrated a moderate-sized
bladder, partially competent bladder neck, and no vesicoureteral reflux. A
modified Cantwell-Ransley approach to the repair was performed without complete
disassembly of the penis. Established surgical principles of identification of
laterally placed neurovascular bundles, preservation of the ventral mesentery to
the urethral plate, mobilization of the urethral plate off the corporal bodies
with ventral relocation, and dorsal medial rotation of the corporal bodies are
demonstrated in this video. RESULTS: This procedure was performed as an
outpatient. The patient had an unremarkable postoperative course. The #6-French
urethral stent was removed on postoperative day 10. CONCLUSIONS: This video
demonstrates a modified Cantwell-Ransley technique for epispadias repair, which
employs a tunica vaginalis flap to reinforce the urethral repair. The adherence
to surgical principles described by Cantwell in the late 1800s for children with
primary epispadias continues to lead optimal surgical outcomes.
PMID- 28689650
TI - Relative contribution of porcine reproductive and respiratory syndrome virus open
reading frames 2-4 to the induction of protective immunity.
AB - The minor glycoproteins (GPs) of PRRSV, GP2, GP3, and GP4, form a heterotrimer
that is required for viral infectivity, presumably due to its interaction with
the key cellular receptor CD163. These 3GPs are encoded by open reading frames
(ORFs) 2a, 3 and 4 (herein referred to as ORFs 2-4), respectively. The goal of
this study was to investigate the immunogenicity of the PRRSV-2 minor GPs.
Through the use of reverse genetics, a chimeric virus (designated SDFL24) was
constructed by replacing ORFs 2-4 of the PRRSV-1 strain SD01-08 with the
corresponding genes of the PRRSV-2 strain FL12. While the parental PRRSV strain
SD01-08 was not neutralized by convalescent antisera raised against FL12, the
chimeric virus SDFL24 gained susceptibility to neutralization by FL12-specific
antisera, indicating that viral proteins encoded by ORFs 2-4 are targets of
antibody neutralization. When inoculated into pigs, the chimeric virus SDFL24
elicited T-cell responses against peptides derived from FL12 minor GPs, whereas
the parental virus SD01-08 did not. After challenge infection with FL12, pigs
previously infected with SDFL24 developed robust kinetics of FL12-specific
neutralizing antibodies as compared to those previously infected with the
parental strain SD01-08. Finally, the pigs recovered from SDFL24 infection were
better protected from a subsequent challenge infection with FL12 than those
previously infected with SD01-08. Collectively, the results indicate that PRRSV-2
ORFs 2-4 are capable of inducing protective immunity.
PMID- 28689651
TI - Frequencies of peripheral immune cells in older adults following seasonal
influenza vaccination with an adjuvanted vaccine.
AB - As age increases, immune responses and consequently protection following
vaccination to seasonal influenza is commonly believed to decrease. Possible
drivers of this immune dysfunction include immunosenescence, repeated exposure to
the same seasonal influenza antigens, and prior infection with cytomegalovirus
(CMV). Here, to determine immune parameters distinguishing vaccine humoral
responders (R) from non-responders (NR) following vaccination, we surveyed broad
peripheral blood "cellular immune correlates" of older adults vaccinated with
Fluad(r) (an adjuvanted subunit influenza vaccine containing strains H1N1, H3N2
and B). Phenotyping included alphabeta-T-cells, gammadelta-T-cells, B-cells and
myeloid cells. The frequencies of most of these lymphocyte phenotypes were found
to be similar in R and NR, although perhaps counterintuitively, one of the few
differences seen between the two groups was higher frequencies of regulatory T
cells in R. These differences were more prominent for responses to the vaccine
strains H1N1 and H3N2 than to the B strain, and in CMV-seropositive than CMV
seronegative elderly. Further, frequencies of early-differentiated CD4+ T-cells
tended to be higher and frequencies of memory CD4+ T-cells tended to be lower in
R than NR. There were also differences in B-cells, with higher frequencies in R
compared to NR. To the best of our knowledge, these results are the first to
report such differences in elderly people responding or failing to respond to
adjuvanted seasonal influenza vaccination.
PMID- 28689652
TI - Field evaluation of candidate baits for oral delivery of BCG vaccine to European
badgers, Meles meles.
AB - The control of tuberculosis (TB) in cattle in the UK and Ireland is compromised
by transmission of Mycobacterium bovis to cattle from the European badger (Meles
meles), which acts as a wildlife reservoir. Vaccination of badgers could
potentially contribute to TB control but the only licensed vaccine is injectable
BadgerBCG which requires the live-capture of badgers. Current research is aimed
at developing an oral TB vaccine (where vaccine is contained within bait) that is
intended to be more cost-effective to deploy over large areas. In order to
identify a lead product, candidate baits identified from captive badger studies
were evaluated in three successive bait screening studies with wild badgers. A
fourth field study, using the lead candidate bait and biomarkers, investigated
the effectiveness of different carriers for their potential to deliver liquid
payloads (vaccine surrogate). In each field study, bait disappearance was
monitored daily for ten days and remote video surveillance was used to determine
preference (i.e. the order in which baits were taken). In the carrier study,
biomarkers were used to determine what proportion of subsequently trapped badgers
had ingested the bait and the vaccine-carrier biomarker payload. Across all four
studies, 79% (3397/4330) of baits were taken by badgers although the number
varied significantly by badger social group and bait type. In all studies, bait
disappearance increased over time, with 75-100% of baits being taken by day ten.
In the carrier study, 75% (9/12) of trapped badgers tested positive for at least
one of the biomarkers and the type of carrier did not influence bait
attractiveness. Together with data from complementary laboratory and captive
animal studies, this study identified a highly attractive and palatable bait
(peanut-based paste bait; PT) and vaccine-carrier (hydrogenated peanut oil; HPO)
combination with the potential to deliver a liquid vaccine to wild badgers.
PMID- 28689653
TI - WHO position on the use of fractional doses - June 2017, addendum to vaccines and
vaccination against yellow fever WHO: Position paper - June 2013.
AB - This article presents the World Health Organization's (WHO) recommendations on
the use of fractional doses of yellow fever vaccines excerpted from the "Yellow
fever vaccine: WHO position on the use of fractional doses - June 2017, Addendum
to Vaccines and vaccination against yellow fever WHO: Position Paper - June
2013", published in the Weekly Epidemiological Record [1,2]. This addendum to the
2013 position paper pertains specifically to use of fractional dose YF (fYF)
vaccination (fractional dose yellow fever vaccination refers to administration of
a reduced volume of vaccine dose, which has been reconstituted as usual per
manufacturer recommendations) in the context of YF vaccine supply shortages
beyond the capacity of the global stockpile. The current WHO position on the use
of yellow fever (YF) vaccine is set out in the 2013 WHO position paper on
vaccines and vaccination against YF and those recommendations are unchanged.
Footnotes to this paper provide a number of core references including references
to grading tables that assess the quality of the scientific evidence, and to the
evidence-to-recommendation table. In accordance with its mandate to provide
guidance to Member States on health policy matters, WHO issues a series of
regularly updated position papers on vaccines and combinations of vaccines
against diseases that have an international public health impact. These papers
are concerned primarily with the use of vaccines in large-scale immunization
programmes; they summarize essential background information on diseases and
vaccines, and conclude with WHO's current position on the use of vaccines in the
global context. Recommendations on the use of Yellow Fever vaccines were
discussed by SAGE in October 2016; evidence presented at these meetings can be
accessed at:
www.who.int/immunization/sage/meetings/2016/October/presentations_background_docs
en/.
PMID- 28689654
TI - Low accuracy and reproducibility of melanoma diagnoses.
PMID- 28689655
TI - Robotic Resection of a Symptomatic Parasitic Leiomyoma From the Obturator Fossa.
AB - STUDY OBJECTIVE: To demonstrate a technique for robotically resecting a parasitic
leiomyoma from the obturator fossa. DESIGN: Case report and a step-by-step video
demonstration of resection of a symptomatic parasitic leiomyoma (Canadian Task
Force classification III). SETTING: Tertiary referral center in New Haven,
Connecticut. INTERVENTIONS: This 48-year-old Caucasian female had undergone a
previous total abdominal hysterectomy for uterine leiomyomas. She presented to
her primary care provider with lower back pain radiating to the right groin and
with a burning sensation on the medial aspect of the inner thigh. She denied any
decrease in leg muscle strength. Pelvic magnetic resonance imaging revealed a 3.3
cm mass in the obturator fossa compressing the obturator nerve. She was
subsequently referred to gynecologic oncology for resection of the mass, and was
brought to the operating room for robotic resection. Once retroperitoneum on the
right pelvic sidewall was explored, ureterolysis was performed. The external
iliac artery and vein were then mobilized medially to access the obturator fossa.
The mass was visualized at the sidewall. Safe resection of the obturator fossa
mass requires identification of the obturator nerve. The specimen was resected
off the right pelvic sidewall with traction-countertraction, gentle wiping, and
grasping-tenting techniques. It was then placed in a laparoscopic bag and removed
from the peritoneal cavity in a contained manner. The procedure was performed
without any complications. The patient had an uneventful postoperative course and
was discharged to home on postoperative day 0. Pathology revealed a benign
leiomyoma. The patient was symptom-free at her 4-week postoperative visit.
CONCLUSION: Robotic resection of a symptomatic retroperitoneal mass in the
obturator fossa was successfully performed, with resulting resolution of
obturator neuropathy. Parasitic leiomyomas should be considered in the
differential diagnosis for a patient presenting with an intraperitoneal or
retroperitoneal mass with a history of previous surgery for leiomyomas.
PMID- 28689656
TI - Body Temperature Cycles Control Rhythmic Alternative Splicing in Mammals.
AB - The core body temperature of all mammals oscillates with the time of the day.
However, direct molecular consequences of small, physiological changes in body
temperature remain largely elusive. Here we show that body temperature cycles
drive rhythmic SR protein phosphorylation to control an alternative splicing (AS)
program. A temperature change of 1 degrees C is sufficient to induce a concerted
splicing switch in a large group of functionally related genes, rendering this
splicing-based thermometer much more sensitive than previously described
temperature-sensing mechanisms. AS of two exons in the 5' UTR of the TATA-box
binding protein (Tbp) highlights the general impact of this mechanism, as it
results in rhythmic TBP protein levels with implications for global gene
expression in vivo. Together our data establish body temperature-driven AS as a
core clock-independent oscillator in mammalian peripheral clocks.
PMID- 28689657
TI - Wnt-Dependent Inactivation of the Groucho/TLE Co-repressor by the HECT E3
Ubiquitin Ligase Hyd/UBR5.
AB - Extracellular signals are transduced to the cell nucleus by effectors that bind
to enhancer complexes to operate transcriptional switches. For example, the Wnt
enhanceosome is a multiprotein complex associated with Wnt-responsive enhancers
through T cell factors (TCF) and kept silent by Groucho/TLE co-repressors. Wnt
activated beta-catenin binds to TCF to overcome this repression, but how it
achieves this is unknown. Here, we discover that this process depends on the HECT
E3 ubiquitin ligase Hyd/UBR5, which is required for Wnt signal responses in
Drosophila and human cell lines downstream of activated Armadillo/beta-catenin.
We identify Groucho/TLE as a functionally relevant substrate, whose
ubiquitylation by UBR5 is induced by Wnt signaling and conferred by beta-catenin.
Inactivation of TLE by UBR5-dependent ubiquitylation also involves VCP/p97, an
AAA ATPase regulating the folding of various cellular substrates including
ubiquitylated chromatin proteins. Thus, Groucho/TLE ubiquitylation by Hyd/UBR5 is
a key prerequisite that enables Armadillo/beta-catenin to activate transcription.
PMID- 28689658
TI - Conformational Landscape of the p28-Bound Human Proteasome Regulatory Particle.
AB - The proteasome holoenzyme is activated by its regulatory particle (RP) consisting
of two subcomplexes, the lid and the base. A key event in base assembly is the
formation of a heterohexameric ring of AAA-ATPases, which is guided by at least
four RP assembly chaperones in mammals: PAAF1, p28/gankyrin, p27/PSMD9, and S5b.
Using cryogenic electron microscopy, we analyzed the non-AAA structure of the p28
bound human RP at 4.5 A resolution and determined seven distinct conformations of
the Rpn1-p28-AAA subcomplex within the p28-bound RP at subnanometer resolutions.
Remarkably, the p28-bound AAA ring does not form a channel in the free RP and
spontaneously samples multiple "open" and "closed" topologies at the Rpt2-Rpt6
and Rpt3-Rpt4 interfaces. Our analysis suggests that p28 assists the proteolytic
core particle to select a specific conformation of the ATPase ring for RP
engagement and is released in a shoehorn-like fashion in the last step of the
chaperone-mediated proteasome assembly.
PMID- 28689659
TI - Bcl3 Phosphorylation by Akt, Erk2, and IKK Is Required for Its Transcriptional
Activity.
AB - Unlike prototypical IkappaB proteins, which are inhibitors of NF-kappaB RelA,
cRel, and RelB dimers, the atypical IkappaB protein Bcl3 is primarily a
transcriptional coregulator of p52 and p50 homodimers. Bcl3 exists as phospho
protein in many cancer cells. Unphosphorylated Bcl3 acts as a classical IkappaB
like inhibitor and removes p50 and p52 from bound DNA. Neither the
phosphorylation site(s) nor the kinase(s) phosphorylating Bcl3 is known. Here we
show that Akt, Erk2, and IKK1/2 phosphorylate Bcl3. Phosphorylation of Ser33 by
Akt induces switching of K48 ubiquitination to K63 ubiquitination and thus
promotes nuclear localization and stabilization of Bcl3. Phosphorylation by Erk2
and IKK1/2 of Ser114 and Ser446 converts Bcl3 into a transcriptional coregulator
by facilitating its recruitment to DNA. Cells expressing the S114A/S446A mutant
have cellular proliferation and migration defects. This work links Akt and MAPK
pathways to NF-kappaB through Bcl3 and provides mechanistic insight into how Bcl3
functions as an oncoprotein through collaboration with IKK1/2, Akt, and Erk2.
PMID- 28689660
TI - Structure of Full-Length SMC and Rearrangements Required for Chromosome
Organization.
AB - Multi-subunit SMC complexes control chromosome superstructure and promote
chromosome disjunction, conceivably by actively translocating along DNA double
helices. SMC subunits comprise an ABC ATPase "head" and a "hinge" dimerization
domain connected by a 49 nm coiled-coil "arm." The heads undergo ATP-dependent
engagement and disengagement to drive SMC action on the chromosome. Here, we
elucidate the architecture of prokaryotic Smc dimers by high-throughput cysteine
cross-linking and crystallography. Co-alignment of the Smc arms tightly closes
the interarm space and misaligns the Smc head domains at the end of the rod by
close apposition of their ABC signature motifs. Sandwiching of ATP molecules
between Smc heads requires them to substantially tilt and translate relative to
each other, thereby opening up the Smc arms. We show that this mechanochemical
gating reaction regulates chromosome targeting and propose a mechanism for DNA
translocation based on the merging of DNA loops upon closure of Smc arms.
PMID- 28689662
TI - Activation of the Unfolded Protein Response by Lipid Bilayer Stress.
AB - The unfolded protein response (UPR) is a conserved homeostatic program that is
activated by misfolded proteins in the lumen of the endoplasmic reticulum (ER).
Recently, it became evident that aberrant lipid compositions of the ER membrane,
referred to as lipid bilayer stress, are equally potent in activating the UPR.
The underlying molecular mechanism, however, remained unclear. We show that the
most conserved transducer of ER stress, Ire1, uses an amphipathic helix (AH) to
sense membrane aberrancies and control UPR activity. In vivo and in vitro
experiments, together with molecular dynamics (MD) simulations, identify the
physicochemical properties of the membrane environment that control Ire1
oligomerization. This work establishes the molecular mechanism of UPR activation
by lipid bilayer stress.
PMID- 28689661
TI - Nuclear Acetyl-CoA Production by ACLY Promotes Homologous Recombination.
AB - While maintaining the integrity of the genome and sustaining bioenergetics are
both fundamental functions of the cell, potential crosstalk between metabolic and
DNA repair pathways is poorly understood. Since histone acetylation plays
important roles in DNA repair and is sensitive to the availability of acetyl
coenzyme A (acetyl-CoA), we investigated a role for metabolic regulation of
histone acetylation during the DNA damage response. In this study, we report that
nuclear ATP-citrate lyase (ACLY) is phosphorylated at S455 downstream of ataxia
telangiectasia mutated (ATM) and AKT following DNA damage. ACLY facilitates
histone acetylation at double-strand break (DSB) sites, impairing 53BP1
localization and enabling BRCA1 recruitment and DNA repair by homologous
recombination. ACLY phosphorylation and nuclear localization are necessary for
its role in promoting BRCA1 recruitment. Upon PARP inhibition, ACLY silencing
promotes genomic instability and cell death. Thus, the spatial and temporal
control of acetyl-CoA production by ACLY participates in the mechanism of DNA
repair pathway choice.
PMID- 28689663
TI - New hepatitis C antiviral treatments eliminate the virus.
PMID- 28689665
TI - Determining the burden of respiratory syncytial virus disease: the known and the
unknown.
PMID- 28689666
TI - Incidence rates and risks of diethylstilbestrol-related clear-cell adenocarcinoma
of the vagina and cervix: Update after 40-year follow-up.
AB - OBJECTIVE: Women exposed to diethylstilbestrol (DES) in utero are at increased
risk for the development of vaginal and cervical clear cell adenocarcinoma (CCA)
at younger age. It is unknown if a second peak will occur in later life, the ages
when CCA developed spontaneously in the pre-DES era. The complete epidemiologic
curve of CCA has not been reported, yet. METHODS: We reviewed 720 cases of CCA
from the CCA registry at the University of Chicago through 2014. Incidence rates
and cumulative risks for CCA were calculated based on white women born in the
U.S. from 1948 through 1971. RESULTS: In 420 CCA cases there was documented
evidence of prenatal DES exposure. 80% were among those between ages 15 and 31
but some occurred as late as age 55. A small second peak occurred around age 42.
The risk of DES-related CCA was highest in the 1951-1956 birth cohort and this
birth cohort effect closely correlated with DES prescriptions over time in the
U.S. (r=0.98, P=0.005). By age 50, the cumulative risk of CCA was 1 per 750
exposed women. CCA cases without evidence of DES exposure had similar ages, year
of diagnosis, and birth cohort patterns as the documented DES-exposed cases,
suggesting that some negative cases were exposed. Their inclusion raises the
cumulative risk of CCA to 1 per 520. CONCLUSION: With the largest data available,
our results confirmed the association between prenatal DES exposure and clear
cell adenocarcinoma. The study also refines the risks of DES-related CCA.
PMID- 28689667
TI - Is hormonal therapy effective in advanced endometrial cancer? A systematic review
and meta-analysis.
AB - BACKGROUND: Hormonal therapy (HT) is used commonly in the treatment of advanced
endometrial cancer (EC). However, a 2010 Cochrane Review did not show a survival
benefit for HT. Here, we quantify its effects and explore the influence of
clinico-pathologic factors and hormone receptor (HR) status on overall response
rates (ORR). METHODS: A systematic search of electronic databases identified
publications of HT in advanced EC. Data from individual studies reporting ORR,
median progression-free (PFS) or overall survival (OS) were weighted by
individual study sample size and pooled in a meta-analysis. Outcomes of estrogen
(ER) and progesterone receptor (PgR) subgroups were collected. Studies of first-
and second-line HT were analyzed independently. Mixed studies were included if
subgroup data based on previous HT exposure were provided. Meta-regression was
performed to evaluate the influence of clinico-pathologic factors on outcomes.
RESULTS: Thirty-nine studies were included, with seven providing subgroup data
based on HR status. First-line HT was associated with a mean ORR of 21.6% and
clinical benefit rate (CBR) of 36.7%. Median PFS and OS were 2.8 and 10.2months
respectively. ORR was 20.4% in clinical trials and 25.3% in observational
studies. Magnitude of ORR was lower in older age, adenosquamous histology and
high grade. ORR was higher in ER+ (26.5%) and PgR+ (35.5%) disease, and lower in
ER- (9.2%) or PgR- (12.1%) tumors. Second-line ORR was 18.5%. CBR was 35.8%, but
was significantly associated with timing of stable disease assessments in first-
and second-line. Meta-regression performed in mixed and second-line studies
showed an association between previous HT and greater ORR (beta 0.561; p=0.024),
suggesting potential confounding by indication (re-treatment of good responders
to first-line HT). CONCLUSION: HT is associated with modest ORR in advanced EC,
and is greatest in HR+ tumors. Response rates in second-line are likely dependent
on response to previous HT.
PMID- 28689668
TI - Factors influencing clinical trial enrollment among ovarian cancer patients.
AB - OBJECTIVE: To characterize patients who did not enroll on a clinical trial and
identify barriers that may limit enrollment among patients with advanced
epithelial ovarian cancer (EOC) presenting for first-line chemotherapy. METHODS:
We conducted a retrospective review of patients diagnosed with stage II-IV EOC
from 10/2009-4/2013, a time period during which multiple trials were available to
all EOC patients, including optimally debulked, suboptimally debulked, or
undergoing neoadjuvant chemotherapy. Enrollment status, demographics, tumor
characteristics, and treatment details were recorded. SAS version 9.3 was used
for all analyses. RESULTS: 144 patients met study criteria; 67% were enrolled on
a trial. Enrolled patients were significantly younger (median 61 vs 68years,
p=0.002). Stage (p=0.30), race (p=0.75), and performance status (p=0.38) were
similar between enrolled and non-enrolled patients. Distance did not impact
enrollment, as nearly half of patients in both groups lived >50miles from the
treatment center (39.0% vs 47.8%, p=0.36). Mode of chemotherapy administration
significantly differed based on participation (all p<0.05). Despite similar
residual disease status (p=1.00) and number of chemotherapy regimens received
(p=0.59), patients treated on trial had a higher 3-year survival rate (70.7% vs
51.7%, p=0.031). The difference in median progression-free survival approached
significance (20.2 vs 9.2months, p=0.091). CONCLUSION: In an institution where
the culture is to offer clinical trials to all eligible patients, 33% of front
line EOC patients did not participate. Increasing age was associated with non
participation. Modifiable barriers must be overcome so that trial enrollment can
better reflect true EOC demographics.
PMID- 28689669
TI - Low serum selenium is associated with the severity of organ failure in critically
ill children.
AB - BACKGROUND & AIMS: Low concentration of serum selenium is associated with the
inflammatory response and multiple organ failure in adult ICU-patients.
Critically ill children are less well characterized. In this study, serum
selenium concentration and its possible relation to multiple organ failure as
well as glutathione status was investigated in pediatric intensive care (PICU)
patients. METHODS: A prospective consecutive cohort of critically ill children (n
= 100) admitted to the PICU of a tertiary university hospital, and in addition an
age stratified reference group of healthy children (n = 60) were studied. The
concentrations of serum selenium and reduced and total glutathione were
determined at admission and at day 5 for patients still in the PICU. RESULTS: Low
concentration of serum selenium as well as a high-reduced fraction of glutathione
(GSH/tGSH) was associated with multiple organ failure (p < 0.001 and p < 0.01)
respectively. A correlation between low serum selenium concentration and high
reduced fraction of glutathione (GSH/tGSH) was also seen (r = -0.19 and p =
0.03). The serum selenium concentrations in the pediatric reference group in a
selenium poor area were age dependent with lower concentrations in infants as
compared to older children (p < 0.001). CONCLUSIONS: Both low serum selenium
concentration and high reduced fraction of glutathione (GSH/tGSH) were associated
with the development of multiple organ failure. The association between low serum
selenium concentration and high fraction of reduced glutathione in whole blood
favour the hypothesis that selenium is of critical importance for the scavenge
capacity of glutathione peroxidase (GPX).
PMID- 28689664
TI - Global, regional, and national disease burden estimates of acute lower
respiratory infections due to respiratory syncytial virus in young children in
2015: a systematic review and modelling study.
AB - BACKGROUND: We have previously estimated that respiratory syncytial virus (RSV)
was associated with 22% of all episodes of (severe) acute lower respiratory
infection (ALRI) resulting in 55 000 to 199 000 deaths in children younger than 5
years in 2005. In the past 5 years, major research activity on RSV has yielded
substantial new data from developing countries. With a considerably expanded
dataset from a large international collaboration, we aimed to estimate the global
incidence, hospital admission rate, and mortality from RSV-ALRI episodes in young
children in 2015. METHODS: We estimated the incidence and hospital admission rate
of RSV-associated ALRI (RSV-ALRI) in children younger than 5 years stratified by
age and World Bank income regions from a systematic review of studies published
between Jan 1, 1995, and Dec 31, 2016, and unpublished data from 76 high quality
population-based studies. We estimated the RSV-ALRI incidence for 132 developing
countries using a risk factor-based model and 2015 population estimates. We
estimated the in-hospital RSV-ALRI mortality by combining in-hospital case
fatality ratios with hospital admission estimates from hospital-based (published
and unpublished) studies. We also estimated overall RSV-ALRI mortality by
identifying studies reporting monthly data for ALRI mortality in the community
and RSV activity. FINDINGS: We estimated that globally in 2015, 33.1 million
(uncertainty range [UR] 21.6-50.3) episodes of RSV-ALRI, resulted in about 3.2
million (2.7-3.8) hospital admissions, and 59 600 (48 000-74 500) in-hospital
deaths in children younger than 5 years. In children younger than 6 months, 1.4
million (UR 1.2-1.7) hospital admissions, and 27 300 (UR 20 700-36 200) in
hospital deaths were due to RSV-ALRI. We also estimated that the overall RSV-ALRI
mortality could be as high as 118 200 (UR 94 600-149 400). Incidence and
mortality varied substantially from year to year in any given population.
INTERPRETATION: Globally, RSV is a common cause of childhood ALRI and a major
cause of hospital admissions in young children, resulting in a substantial burden
on health-care services. About 45% of hospital admissions and in-hospital deaths
due to RSV-ALRI occur in children younger than 6 months. An effective maternal
RSV vaccine or monoclonal antibody could have a substantial effect on disease
burden in this age group. FUNDING: The Bill & Melinda Gates Foundation.
PMID- 28689670
TI - ESPEN expert group recommendations for action against cancer-related
malnutrition.
AB - Patients with cancer are at particularly high risk for malnutrition because both
the disease and its treatments threaten their nutritional status. Yet cancer
related nutritional risk is sometimes overlooked or under-treated by clinicians,
patients, and their families. The European Society for Clinical Nutrition and
Metabolism (ESPEN) recently published evidence-based guidelines for nutritional
care in patients with cancer. In further support of these guidelines, an ESPEN
oncology expert group met for a Cancer and Nutrition Workshop in Berlin on
October 24 and 25, 2016. The group examined the causes and consequences of cancer
related malnutrition, reviewed treatment approaches currently available, and
built the rationale and impetus for clinicians involved with care of patients
with cancer to take actions that facilitate nutrition support in practice. The
content of this position paper is based on presentations and discussions at the
Berlin meeting. The expert group emphasized 3 key steps to update nutritional
care for people with cancer: (1) screen all patients with cancer for nutritional
risk early in the course of their care, regardless of body mass index and weight
history; (2) expand nutrition-related assessment practices to include measures of
anorexia, body composition, inflammatory biomarkers, resting energy expenditure,
and physical function; (3) use multimodal nutritional interventions with
individualized plans, including care focused on increasing nutritional intake,
lessening inflammation and hypermetabolic stress, and increasing physical
activity.
PMID- 28689671
TI - Detection of toxigenic Clostridium difficile in paediatric patients.
AB - INTRODUCTION: Our main objective was a revision of clinical, microbiological and
epidemiological results of Clostridium difficile-associated infection in
paediatric patients (2010-2015). We compared the diagnoses performed by detection
of toxins in feces and those performed by real-time PCR. METHODS: This
retrospective study included 82 paediatric patients. Detection of toxigenic C.
difficile was performed sequentially, in diarrheal feces and under clinical
request. RESULTS: A total of 39% of the patients were attended at Haematology
oncology Unit and >50% of them had previously received cephalosporins. Fever
associated with diarrhea was more frequent in the group of toxin detection,
whereas not receiving specific antibiotic treatment was more frequent in the
group of positive PCR, without statistically significant differences.
CONCLUSIONS: We highlight the presence of C. difficile infection in children
under 2years old. A diagnostic testing in selected paediatric patients would be
advisable when there is clinical suspicion of infection.
PMID- 28689672
TI - Extended screening of Trypanosoma cruzi among the offspring of infected women.
Barcelona North metropolitan area, Catalonia (Spain), 2005-2016.
AB - INTRODUCTION: To date, very little data is available on the extensive, familiar,
serological screening of Trypanosoma cruzi from infected-index cases. As it is a
parasite with possibility of mother-to-child fetal transmission, the study of the
offspring of chronically infected women has a special relevance. METHODS: An
observational study using a capture-recapture method that evaluates the offspring
serological status of women diagnosed with T. cruzi infection (positive serology)
in the northern metropolitan area of Barcelona during 2005-2016. RESULTS: A total
of 238 women with positive serology for T. cruzi were identified. Of these, 117
(49.2%) could be localized. Their offspring summarized 300 individuals, of which
192 (64%) had serology records, with 23 positive for T. cruzi (11.98%; CI95%: 8.1
17.3). Among the 53 children born within the study area, 5 (9.8%, CI95%: 4.2
20.9) cases of vertical transmission were recorded. All children born as of 2010
(the starting year of mother screening) had serological outputs. CONCLUSIONS:
Offspring of T. cruzi-seropositive women showed a high rate of seropositivity.
The prevalence of vertical transmission is also remarkably high but comparable to
that obtained in other European studies. The main source of loss was non
accessible women. It is reasonable to formaly include extensive, familiar,
serological assessment in Chagas screening guidelines. In order to avoid losses,
any eventual screening should be implemented at the time of the maternal
diagnosis.
PMID- 28689675
TI - Hypothesis of Improved Visualization of Microstructures in the Interventricular
Septum with Ultrasound and Adaptive Beamforming.
AB - In this work, in vivo ultrasound cardiac images created with Capon's minimum
variance adaptive beamformer are compared with images acquired with the
conventional delay-and-sum beamformer. Specifically, we provide three views of a
human heart imaged through the parasternal short-axis, the parasternal long-axis
and the apical four-chamber views. The minimum variance beamformer produced
images with improved lateral resolution, resulting in better resolved speckle
structure and improved edges, especially on close investigation of the
interventricular septum. These improvements in image quality might possibly
improve the visualization of microstructures in the human heart.
PMID- 28689674
TI - Determination of immune status in dogs against CPV-2 by recombinant protein based
latex agglutination test.
AB - Canine parvoviral enteritis is a highly contagious viral illness caused by canine
parvovirus-2 (CPV-2) which affects puppies of mainly 6-20 weeks of age.
Vaccination is pivotal in preventing and controlling CPV-2 infection.
Determination of antibody status is a critical determinant for successful
vaccination. The hemagglutination inhibition (HI) test is 'gold standard' test
for quantification of antibodies specific to CPV-2, although the execution of
this test is not feasible under field conditions. The present study was
undertaken to develop a point of care testing to determine immune status prior to
CPV-2 vaccination or to detect seroconversion in immunized dogs by latex
agglutination test (LAT) using recombinant antigen. Truncated portion of VP2
protein (tVP2) of CPV-2 was selected on the basis of antigenic indices,
overexpressed the recombinant protein in E. coli system and was subsequently used
in development of LAT. A total of 59 serum samples obtained from vaccinated (n =
54) and healthy unvaccinated (n = 5) dogs were tested. The positivity was
observed in 85% (46/54) of these dogs with varying agglutination pattern. The
overall sensitivity and specificity of latex agglutination test in comparison to
HI test was recorded as 90% and 88% respectively with an agreement value of 90%
(CI = 95%).
PMID- 28689673
TI - The anatomy of apathy: A neurocognitive framework for amotivated behaviour.
AB - Apathy is a debilitating syndrome associated with many neurological disorders,
including several common neurodegenerative diseases such as Parkinson's disease
and Alzheimer's disease, and focal lesion syndromes such as stroke. Here, we
review neuroimaging studies to identify anatomical correlates of apathy, across
brain disorders. Our analysis reveals that apathy is strongly associated with
disruption particularly of dorsal anterior cingulate cortex (dACC), ventral
striatum (VS) and connected brain regions. Remarkably, these changes are
consistent across clinical disorders and imaging modalities. Review of the
neuroimaging findings allows us to develop a neurocognitive framework to consider
potential mechanisms underlying apathy. According to this perspective, an
interconnected group of brain regions - with dACC and VS at its core - plays a
crucial role in normal motivated behaviour. Specifically we argue that motivated
behaviour requires a willingness to work, to keep working, and to learn what is
worth working for. We propose that deficits in any one or more of these processes
can lead to the clinical syndrome of apathy, and outline specific approaches to
test this hypothesis. A richer neurobiological understanding of the mechanisms
underlying apathy should ultimately facilitate development of effective therapies
for this disabling condition.
PMID- 28689676
TI - Health anxiety and medical utilization: The moderating effect of age among
patients in primary care.
AB - Health anxiety is commonly seen in medical clinics and is related to the
overutilization of primary care services, but existing studies have not yet
considered the possible moderating effect of age. We examined if age moderated
the association between health anxiety and medical utilization. A secondary aim
was to examine potential racial/ethnic differences in health anxiety. An
ethnoracially diverse group of patients (N=533) seeking treatment from a primary
care clinic completed a self-report measure of health anxiety. Three indices of
medical utilization were assessed using medical records, including the number of:
(a) clinic visits over the past two years, (b) current medications, and (c) lab
tests over the past two years. Age moderated the effect of health anxiety on
multiple indices of medical utilization. Supplemental analyses found that the
moderating effect of age was specific to a somatic/body preoccupation, rather
than health worry, dimension of health anxiety. Mean-level differences in health
anxiety were either not supported (health anxiety composite, somatic/body
preoccupation) or were small in magnitude (health worry) among self-identifying
Black, Latino, and White participants. Results indicate that assessing for health
anxiety could be particularly important for older adult patients who frequently
seek out medical services.
PMID- 28689677
TI - Walking with blood flow restriction: Could it help the elderly to get more out of
every step?
PMID- 28689678
TI - Exercise-intensity dependent alterations in plasma redox status do not reflect
skeletal muscle redox-sensitive protein signaling.
AB - OBJECTIVES: Redox homeostasis and redox-sensitive protein signaling play a role
in exercise-induced adaptation. The effects of sprint-interval exercise (SIE),
high-intensity interval exercise (HIIE) and continuous moderate-intensity
exercise (CMIE), on post-exercise plasma redox status are unclear. Furthermore,
whether post-exercise plasma redox status reflects skeletal muscle redox
sensitive protein signaling is unknown. DESIGN: In a randomized crossover design,
eight healthy adults performed a cycling session of HIIE (5*4min at 75% Wmax),
SIE (4*30s Wingate's), and CMIE work-matched to HIIE (30min at 50% of Wmax).
METHODS: Plasma hydrogen peroxide (H2O2), thiobarbituric acid reactive substances
(TBARS), superoxide dismutase (SOD) activity, and catalase activity were measured
immediately post, 1h, 2h and 3h post-exercise. Plasma redox status biomarkers
were correlated with phosphorylation of skeletal muscle p38-MAPK, JNK, NF-kappaB,
and IkappaBalpha protein content immediately and 3h post-exercise. RESULTS:
Plasma catalase activity was greater with SIE (56.6+/-3.8Uml-1) compared to CMIE
(42.7+/-3.2, p<0.01) and HIIE (49.0+/-5.5, p=0.07). Peak plasma H2O2 was
significantly (p<0.05) greater after SIE (4.6+/-0.6nmol/ml) and HIIE (4.1+/-0.4)
compared to CMIE (3.3+/-0.5). Post-exercise plasma TBARS and SOD activity
significantly (p<0.05) decreased irrespective of exercise protocol. A significant
positive correlation was detected between plasma catalase activity and skeletal
muscle p38-MAPK phosphorylation 3h post-exercise (r=0.40, p=0.04). No other
correlations were detected (all p>0.05). CONCLUSIONS: Low-volume SIE elicited
greater post-exercise plasma catalase activity compared to HIIE and CMIE, and
greater H2O2 compared to CMIE. Plasma redox status did not, however, adequately
reflect skeletal muscle redox-sensitive protein signaling.
PMID- 28689679
TI - Non-Invasive Mechanical Ventilation Versus Continuous Positive Airway Pressure
Relating to Cardiogenic Pulmonary Edema in an Intensive Care Unit.
AB - BACKGROUND: To compare the application of non-invasive ventilation (NIV) versus
continuous positive airway pressure (CPAP) in the treatment of patients with
cardiogenic pulmonary edema (CPE) admitted to an intensive care unit (ICU).
METHODS: In a prospective, randomized, controlled study performed in an ICU,
patients with CPE were assigned to NIV (n=56) or CPAP (n=54). Primary outcome was
intubation rate. Secondary outcomes included duration of ventilation, length of
ICU and hospital stay, improvement of gas exchange, complications, ICU and
hospital mortality, and 28-day mortality. The outcomes were analyzed in
hypercapnic patients (PaCO2>45mmHg) with no underlying chronic lung disease.
RESULTS: Both devices led to similar clinical and gas exchange improvement;
however, in the first 60min of treatment a higher PaO2/FiO2 ratio was observed in
the NIV group (205+/-112 in NIV vs. 150+/-84 in CPAP, P=.02). The rate of
intubation was similar in both groups (9% in NIV vs. 9% in CPAP, P=1.0). There
were no differences in duration of ventilation, ICU and length of hospital stay.
There were no significant differences in ICU, hospital and 28-d mortality between
groups. In the hypercapnic group, there were no differences between NIV and CPAP.
CONCLUSIONS: Either NIV or CPAP are recommended in patients with CPE in the ICU.
Outcomes in the hypercapnic group with no chronic lung disease were similar using
NIV or CPAP.
PMID- 28689680
TI - Is low iodine a risk factor for cardiovascular disease in Americans without
thyroid dysfunction? Findings from NHANES.
AB - BACKGROUND AND AIMS: Low body iodine levels are associated with cardiovascular
disease, in part through alterations in thyroid function. While this association
suggested from animal studies, it lacks supportive evidence in humans. This study
examined the association between urine iodine levels and presence of coronary
artery disease (CAD) and stroke in adults without thyroid dysfunction. METHODS
AND RESULTS: This cross-sectional study included 2440 adults (representing a
weighted n = 91,713,183) aged >=40 years without thyroid dysfunction in the
nationally-representative 2007-2012 National Health and Nutrition Examination
Survey. The age and sex-adjusted urine iodine/creatinine ratio (aICR) was
categorized into low (aICR<116 MUg/day), medium (116 MUg/day <= aICR <
370MUg/day), and high (aICR >= 370MUg/day) based on lowest/highest quintiles.
Stroke and CAD were from self-reported physician diagnoses. We examined the
association between low urine aICR and CAD or stroke using multivariable logistic
regression modeling. The mean age of this population was 56.0 years, 47% were
women, and three quarters were non-Hispanic whites. Compared with high urine
iodine levels, multivariable adjusted odds ratios aOR (95% confidence intervals)
for CAD were statistically significant for low, aOR = 1.97 (1.08-3.59), but not
medium, aOR = 1.26 (0.75-2.13) urine iodine levels. There was no association
between stroke and low, aOR = 1.12 (0.52-2.44) or medium, aOR = 1.48 (0.88-2.48)
urine iodine levels. CONCLUSION: The association between low urine iodine levels
and CAD should be confirmed in a prospective study with serial measures of urine
iodine. If low iodine levels precede CAD, then this potential and modifiable new
CAD risk factor might have therapeutic implications.
PMID- 28689681
TI - Locomotion pattern and foot pressure adjustments during gentle turns in healthy
subjects.
AB - People suffering from locomotor impairment find turning manoeuvres more
challenging than straight-ahead walking. Turning manoeuvres are estimated to
comprise a substantial proportion of steps taken daily, yet research has
predominantly focused on straight-line walking, meaning that the basic kinetic,
kinematic and foot pressure adaptations required for turning are not as well
understood. We investigated how healthy subjects adapt their locomotion patterns
to accommodate walking along a gently curved trajectory (radius 2.75m). Twenty
healthy adult participants performed walking tasks at self-selected speeds along
straight and curved pathways. For the first time for this mode of turning,
plantar pressures were recorded using insole foot pressure sensors while
participants' movements were simultaneously tracked using marker-based 3D motion
capture. During the steady-state strides at the apex of the turn, the mean
operating point of the inside ankle shifted by 1 degree towards dorsiflexion and
that for the outside ankle shifted towards plantarflexion. The largest change in
relative joint angle range was an increase in hip rotation in the inside leg
(>60%). In addition, the inside foot was subject to a prolonged stance phase and
a 10% increase in vertical force in the posteromedial section of the foot
compared to straight-line walking. Most of the mechanical change required was
therefore generated by the inside leg with hip rotation being a major driver of
the gentle turn. This study provides new insight into healthy gait during gentle
turns and may help us to understand the mechanics behind some forms of
impairment.
PMID- 28689683
TI - Reply to Burn and Sheth
PMID- 28689682
TI - Vaginal versus Robotic Hysterectomy for Commonly Cited Relative Contraindications
to Vaginal Hysterectomy.
AB - STUDY OBJECTIVE: To compare outcomes of vaginal hysterectomy (VH) and robotic
assisted hysterectomy (RH) among women with conditions perceived as
contraindications to VH (uterine size >= 12 weeks' gestation, no vaginal parity,
prior cesarean delivery, and obesity). DESIGN: Retrospective chart review
(Canadian Task Force classification II-2). SETTING: Tertiary US medical center.
PATIENTS: Women with VH or RH. Women with conditions perceived as
contraindications affecting surgical choice were excluded. INTERVENTIONS: VH or
RH for benign uterine disease at our institution during 2009 through 2013.
MEASUREMENTS AND MAIN RESULTS: Among women with the perceived contraindications,
a logistic regression model was fit to compare each binary outcome between VH and
RH. Models were weighted using inverse probability of treatment weights derived
from propensity scores to adjust for covariate imbalance between procedures. The
cohort had 692 VHs and 472 RHs. Among 160 women with uterine size >= 12 weeks'
gestation, RH patients were less likely to have uterine debulking (adjusted odds
ratio [aOR], .37; 95% confidence interval [CI], .15-.95]) than VH patients and
more likely to have accordion grade >= 2 postoperative complications (aOR, 7.20;
95% CI, 1.46-35.42) and readmission (aOR, 15.55; 95% CI. .85-285.20). Among 272
women with prior cesarean section, RH patients were more likely to have grade >=
2 postoperative complications (aOR, 2.85; 95% CI, 1.29-6.30). No outcomes were
significantly different between surgical routes among women with no vaginal
parity or obesity. Mean operative time was significantly longer for RH.
CONCLUSION: VH is a surgical option for patients with the conditions perceived as
contraindications for vaginal surgery evaluated herein.
PMID- 28689684
TI - [Ectopic thymus: A rare cause of neck mass in children].
AB - INTRODUCTION: Ectopic cervical thymus (ECT) is a rare embryological abnormality
in children. It can be revealed by a compressive neck mass mistaken for a
malignant tumor. Through a new case of ECT, we review the embryopathogenesis,
diagnostic difficulties and therapeutic features. CLINICAL OBSERVATION: A 19
month-old girl presented a right cervical mass that quickly increased in size,
causing intermittent dyspnea. The physical examination objectified a 6-cm, soft
and compressible, painless right cervical tumefaction, extending from the mastoid
area to the ipsilateral supraclavicular fossa. The diagnosis suggested based on
CT was a cervicomediastinal cystic lymphangioma. The diagnoses discussed based on
MRI were a collection of necrotic lymphadenopathy, rhabdomyosarcoma or
neurofibroma debris. The mass was surgically excised through a laterocervical
incision. A whitish multilobular tissular mass was found, adherent to the
neurovascular axis of the neck. Pathological examination concluded in normal
ectopic thymus tissue. The postoperative course was uneventful. CONCLUSION:
Although ECT is a rare benign anomaly, it should be considered as a possible
cause of a neck mass in children. Surgery is the curative treatment. Before
surgery, the presence of a mediastinal thymus must be confirmed to avoid the risk
of a total thymectomy in children. MRI is helpful in delineating thymic ectopia
compared to the mediastinal thymus.
PMID- 28689685
TI - [Home and recreational injuries in children under 1year: 10years of experience].
AB - BACKGROUND: There is little research on the prevalence and characteristics of
home and recreational injuries in infants under 12months of age. However,
domestic accidents result in an average of 50 infant deaths in France every year.
METHODS: A descriptive and retrospective study was conducted, based on data from
the permanent investigation on home and recreational injuries in infants under
12months of age (EPAC) published by the Institute for Public Health. Data were
collected from 2004 to 2013 in the pediatric emergency department of Le Havre
hospital. A global quantitative analysis was carried out, as well as age-group
based analyses (groups of infants of similar age within a specific range of
3months of age). RESULTS: A total of 3708 infants under 1year of age were victims
of home and recreational injuries. The incidence of domestic accidents was found
to be an average of one case per day (gender ratio, 1.12). Up to 85% of reported
injuries were found to occur in the home. Falls were the leading cause of home
accidents or injuries (73% of the total number of reported accidents), 7% of
which resulted from a fall from stairs. Children frequently suffered from
concussion or contusions (65%). The neck and head were affected in 73% of cases.
A higher proportion of foreign body injuries occurred after 6months of age
(RR=2.9, p<0.001). The number of hospitalizations decreased with age: 21% of
accidents occurred before 3 months of age; 7% occurred between 9 and 11 months of
age (RR=0.32, p<0.001). Falling from a changing table accounted for 9% of fall
related hospitalizations. CONCLUSIONS: This survey characterized for the first
time the occurrence of home and recreational injuries in infants under 12months
of age in France.
PMID- 28689686
TI - Clinical evaluations of complete autologous fibrin glue, produced by the
CryoSeal(r) FS system, and polyglycolic acid sheets as wound coverings after oral
surgery.
AB - The CryoSeal(r) FS System has been recently introduced as an automated device for
the production of complete fibrin glue from autologous plasma, rather than from
pool allogenic or cattle blood, to prevent viral infection and allergic reaction.
We evaluated the effectiveness of complete autologous fibrin glue and
polyglycolic acid (PGA) sheet wound coverings in mucosa defect oral surgery.
Postoperative pain, scar contracture, ingestion, tongue dyskinesia, and
postoperative bleeding were evaluated in 12 patients who underwent oral
(including the tongue) mucosa excision, and received a PGA sheet and an
autologous fibrin glue covering. They were compared with 12 patients who received
a PGA sheet and commercial allogenic fibrin glue. All cases in the complete
autologous fibrin glue group demonstrated good wound healing without
complications such as local infection or incomplete cure. All evaluated clinical
measures in this group were similar or superior to the commercial allogenic
fibrin glue group. Coagulation and adhesion quality achieved with this method was
comparable to that with a PGA sheet and commercial fibrin glue. Covering oral
surgery wounds with complete autologous fibrin glue produced by an automated
device was convenient, safe, and reduced the risk of viral infection and allergic
reaction associated with conventional techniques.
PMID- 28689687
TI - The effect of the muscarinic M1 receptor antagonist biperiden on cognition in
medication free subjects with psychosis.
AB - The acetylcholine muscarinic M1 receptor has been implicated in both psychosis
and cognition. Post-mortem research has shown reduced muscarinic M1 receptor
density in 25% of chronic patients with schizophrenia. It is unknown whether
reduced M1 receptor density is related to cognitive symptoms of psychosis. We
investigated the role of the M1 receptor in separate cognitive domains in
subjects with a psychotic disorder using a muscarinic M1 antagonist as an acute
pharmacological challenge. 33 young subjects with a psychotic disorder and 30
gender, age and IQ matched healthy controls were enrolled. All participants
completed a comprehensive cognitive test battery twice: once after placebo and
once after oral administration of 4mg. biperiden (M1 antagonist). The order of
drug administration was counterbalanced. Biperiden significantly negatively
influenced both verbal (p< 0.001 and p=0.032) and visual learning and memory
(p=0.028) in both groups. A medication x group interaction effect was found for
reasoning and problem solving (p=0.005). No main or interaction effects were
found for other cognitive domains. These results provide further in-vivo evidence
that the M1 receptor is involved in cognitive functioning, particularly verbal
and visual memory processes. Lack of differential effects of biperiden between
psychotic subjects and healthy controls may suggest that decreased M1 receptor
density is only present in chronic, older schizophrenia patients. However, it
remains possible that differential effects of biperiden would be present in more
severe cognitive impaired subjects with psychosis after several doses of
biperiden instead of a single administration.
PMID- 28689688
TI - Lurasidone in combination with lithium or valproate for the maintenance treatment
of bipolar I disorder.
AB - Lurasidone (DS-RAn) has demonstrated efficacy in the acute treatment of bipolar
depression, both as monotherapy, and as combination therapy with lithium or
valproate. To evaluate the recurrence prevention efficacy of lurasidone for the
maintenance treatment of bipolar I disorder, patients received up to 20 weeks of
open-label lurasidone (20-80mg/d) combined with lithium or valproate during an
initial stabilization phase. A total of 496 patients met stabilization criteria
and were randomized to 28 weeks of double-blind treatment with lurasidone (20
80mg/d) or placebo, in combination with lithium or valproate. Based on a Cox
proportional hazard model, treatment with lurasidone reduced the probability of
recurrence of any mood episode by 29% (primary endpoint), however, the reduction
did not achieve statistical significance. Probability of recurrence on lurasidone
was significantly lower in patients with an index episode of depression (HR,
0.57; P=0.039), in patients with any index episode who were not rapid-cycling
(HR, 0.69; P=0.046), and when recurrence was based on MADRS, YMRS, or CGI-BP-S
severity criteria (HR, 0.53; P=0.025; sensitivity analysis). Long-term treatment
with lurasidone combined with lithium or valproate was found to be safe and well
tolerated, with minimal effects on weight or metabolic parameters.
PMID- 28689689
TI - Serum sodium ion level influenced by daily salt intake after administration of
sodium-glucose cotransporter 2 inhibitors.
PMID- 28689690
TI - Genome analysis of three novel lytic Vibrio coralliilyticus phages isolated from
seawater, Okinawa, Japan.
AB - Three novel Vibrio phages were isolated from seawater in Okinawa. The Vibrio
phage RYC infected Vibrio coralliilyticus SWA 07, while Vibrio phages CKB-S1 and
CKB-S2 infected the coral pathogen V. coralliilyticus P1 (LMG 23696). The Vibrio
phages CKB-S1 and CKB-S2 displayed head-tail structures whereas the Vibrio phage
RYC showed a tailless non-enveloped capsid. All these Vibrio phages contained
linear and double-stranded DNA. The whole genome sequencing revealed that Vibrio
phage RYC has a larger genome size compared to Vibrio phages CKB-S1 and CKB-S2,
and six tRNAs genes were found only in Vibrio phage RYC. Genome-wide comparison
showed that Vibrio phage CKB-S1 was closely related, but was not identical, to
Vibrio parahaemolyticus phages VP16T and VP16C. Meanwhile, the Vibrio phages RYC
and CKB-S2 did not show high genome-wide similarity to any phages. These results
suggest that the Vibrio phages CKB-S1, CKB-S2 and RYC are novel phages, which
need further exploration, especially for their potential applications in phage
therapy.
PMID- 28689691
TI - Variability of homozygous sickle cell disease: The role of alpha and beta globin
chain variation and other factors.
AB - The single base molecular substitution characterizing sickle cell haemoglobin,
beta6glu->val, might be expected to result in predictable haematological and
clinical features. However, the disease manifests remarkable diversity believed
to reflect the interaction with other genetic and environmental factors. Some of
the genetic modifiers include the beta globin haplotypes, alpha thalassaemia,
factors influencing the persistence of fetal haemoglobin and the effects of the
environment are addressed in this review. It is concluded that much of the
genetic data present conflicting results. Environmental factors such as climate
and infections, and psychological, educational and social support mechanisms also
influence expression of the disease. These interactions illustrate how the
expression of a 'single gene' disorder may be influenced by a variety of other
genetic and environmental factors.
PMID- 28689692
TI - Patient and Provider Factors Affecting Clinical Inertia in Patients With Type 2
Diabetes on Metformin Monotherapy.
AB - PURPOSE: Our aim was to determine the extent of clinical inertia and the
associated patient and provider factors in patients with type 2 diabetes on
metformin monotherapy (MM) at a large integrated health care system in the United
States. METHODS: The study cohort included patients with type 2 diabetes aged 18
to 85 years, on MM between January 2009 and September 2013, who experienced MM
failure (had an uncontrolled glycosylated hemoglobin [HbA1c] reading (>=8.0% [64
mmol/mol]) after at least 90 days of MM). Clinical inertia was defined as absence
of treatment intensification with an add-on therapy within 180 days after the MM
failure (index date). The impact of patient and provider factors on clinical
inertia was determined using generalized estimating equations. FINDINGS: The
study cohort consisted of 996 patients; 58% were men and 59% were white, with a
mean age of 53 (11.8) years. Of these, 49.8% experienced clinical inertia. Lower
HbA1c at index date, absence of liver diseases, absence of renal diseases, and
greater provider age were associated with clinical inertia. The clinical inertia
rate in a secondary analysis considering HbA1c <7.0% (53 mmol/mol) as glycemic
control was 67.9%. Greater patient age, lower HbA1c at index date, greater
provider age, and being a primary care physician were associated with clinical
inertia. IMPLICATIONS: Considerable clinical inertia rates were observed in our
real-world patient population, suggesting the need of interventions to reduce
clinical inertia in clinical practice. Information about patient and provider
factors affecting clinical inertia provided by this study could help healthcare
policymakers plan and implement such interventions.
PMID- 28689693
TI - Deprescribing and shared decision making in Internal Medicine.
PMID- 28689694
TI - Is restaging transurethral resection necessary in patients with non-muscle
invasive bladder cancer and limited lamina propria invasion?
AB - OBJECTIVES: To evaluate the influence of lamina propria invasion type at initial
transurethral resection (TUR) on restaging pathology. MATERIALS AND METHODS: We
reviewed prospectively maintained records of all patients with a high-grade pT1
nonmuscle invasive bladder cancer who underwent both initial and restaging TUR
within 6 weeks at our center between 2001 and 2016. The pathology of second TUR
specimens was analyzed with regard to the characteristics of lamina propria
invasion found at initial resection. RESULTS: We included 198 patients, with a
median age of 70 years (interquartile range: 63-79). Muscle was present in the
initial TUR specimen in 107 patients (54%). Pathology restaging was pT0 in 73
patients (37%), pTis in 44 (22%), pTa in 27 (14%), pT1 in 50 (25%), and pT2 in 4
(2%). Eighty-seven patients (44%) had tumors with minimal lamina propria invasion
at initial TUR: 53 specimens (27%) had focal invasion (few malignant cells in the
lamina propria); 15 specimens (7.6%) had superficial invasion (invasion of the
lamina propria to the level of the muscularis mucosae [T1a]); and 19 specimens
(10%) had multifocal superficial invasion (multiple areas of T1a). Of the
patients with minimal lamina propria invasion, residual disease was found in 54
patients (62%). However, none of those patients had T2 disease. CONCLUSIONS: A
significant number of patients with T1 tumors have residual disease at restaging
TUR as do patients with minimal lamina propria invasion. The extent of T1
invasion does not eliminate the need for repeat TUR.
PMID- 28689695
TI - Enhanced sensitivity in detection of antiviral antibody responses using
biotinylation of foot-and-mouth disease virus (FMDV) capsids.
AB - Analysis of the immune response to infection of livestock by foot-and-mouth
disease virus (FMDV) is most often reported as the serum antibody response to the
virus. While measurement of neutralizing antibody has been sensitive and
specific, measurements of the quality of the antibody response are less robust.
Determining the immunoglobulin (Ig) isotype of the serum antibody response
provides a deeper understanding of the biology of the response and more sensitive
methods for these assays will facilitate analyses of B cell mediated immunity. We
tested the hypothesis that using the virus as the molecular probe could be
achieved by adding tags to the surface of the FMDV capsid, and that would enhance
sensitivity in assays for anti-FMDV antibody responses. The use of a FLAG-tagged
virus in these assays failed to yield improvement whereas chemically
biotinylating the virus capsid resulted in significant enhancement of the signal.
Here we describe methods using biotinylated virus for measuring anti-viral
antibody in serum and antibody secreting cells (ASCs) in blood that are sensitive
and specific. Finally, we describe using the biotinylated virus in flow cytometry
where such assays should greatly enhance the analysis of anti-virus antibody
producing B cells, allowing the investigator to focus on only the FMDV specific B
cells when analyzing the development of the B cell response to either infection
or vaccination.
PMID- 28689696
TI - Implementing a Systematic Approach to Improve Governance and Deployment of
Imaging Codes in Radiology.
AB - Unlike medical procedure (Current Procedural Terminology [CPT]) and diagnostic
(International Classification of Diseases [ICD]) codes, imaging (IMG) codes are
defined at the local, institutional level. IMG codes are used within an
organization to define IMG procedures and how they are routed between information
systems. Our purpose is to describe the implementation of a reorganization
(referred to as the IMG code cleanup) and governance structure deployed at a
large children's hospital and the initial effects of that implementation. The
number of IMG codes precleanup was 1388 and postcleanup was 826. This is a
reduction by 40%. The mean number of addendums to radiology reports for billing
reasons per month was 31.7 before and 18.6 after the IMG code cleanup. This
represents a 41% decrease. We believe that the reorganization, standardization of
the approach to naming and coding, reduction in the number of IMG codes, as well
as governance structure put in place to maintain that organization has had both
direct and indirect effects on the department's ability to both provide reliable
IMG services and position the department to improve.
PMID- 28689697
TI - An innovative parameter estimation for fractional order systems with impulse
noise.
AB - This paper investigates the problem of parameter estimation for fractional order
linear systems when the output signal is polluted by impulse noise. The
conventional least square error objective function is replaced by a new
approximate least absolute error (ALAE) function to restrain the influence of
impulse noise. Then a novel parameter estimation approach is designed based on
the stochastic gradient method, the fractional order parameter update law and the
ALAE criterion, which improves estimation accuracy and enhances robustness at the
same time. It is shown that the adoption of the fractional order parameter update
law ensures larger selection range of update order and smoother convergence of
the algorithm. The effectiveness and superiority of the proposed method are
verified by strict mathematical analysis and detailed numerical examples.
PMID- 28689698
TI - Improved fault ride through capability of DFIG based wind turbines using
synchronous reference frame control based dynamic voltage restorer.
AB - Fault ride through (FRT) capability in wind turbines to maintain the grid
stability during faults has become mandatory with the increasing grid penetration
of wind energy. Doubly fed induction generator based wind turbine (DFIG-WT) is
the most popularly utilized type of generator but highly susceptible to the
voltage disturbances in grid. Dynamic voltage restorer (DVR) based external FRT
capability improvement is considered. Since DVR is capable of providing fast
voltage sag mitigation during faults and can maintain the nominal operating
conditions for DFIG-WT. The effectiveness of the DVR using Synchronous reference
frame (SRF) control is investigated for FRT capability in DFIG-WT during both
balanced and unbalanced fault conditions. The operation of DVR is confirmed using
time-domain simulation in MATLAB/Simulink using 1.5MW DFIG-WT.
PMID- 28689699
TI - Robust control of post-stall pitching maneuver based on finite-time observer.
AB - This article presents a robust finite-time maneuver control scheme for the
longitudinal attitude dynamic of the aircraft with unsteady aerodynamic
disturbances and input saturation. To efficiently eliminate the influence of
unsteady aerodynamic disturbances, nonlinear finite-time observers are developed.
Despite the existence of the nonlinearity and the coupling between aircraft
states and unsteady aerodynamic disturbances, the proposed observers can still
precisely estimate the unmeasurable unsteady aerodynamic disturbances in finite
time. To attenuate the effect caused by input saturation, a finite-time auxiliary
system is constructed. With the error between the desired control input and
saturation input as the input of the auxiliary system, the additional signals are
generated to compensate for the effect of input saturation. Combined with the
finite-time observers and the finite-time auxiliary system, a robust finite-time
backstepping attitude control design is developed. The finite-time convergence of
all closed-loop system signals is rigorously proved via Lyapunov analysis method
under the developed robust attitude control schemes. Finally, simulation results
are presented to illustrate the effectiveness of the proposed attitude control
approaches.
PMID- 28689700
TI - Surrounding control of nonlinear multi-agent systems with non-identical agents.
AB - In this paper, the surrounding control problem of a group of non-identical agents
is considered, where a team of followers achieves an equidistant distributed
formation to surround a team of moving leaders. An adaptive design method is
presented for multi-agent systems where the dynamics of agents are supposed to be
nonlinear with unknown parameters. First, an estimator for the center of the
leaders is introduced. Then, two distributed adaptive controllers based on the
estimated center are proposed for each follower. The stability and parameter
convergence of the proposed protocols are shown by using algebraic graph theory
and Lyapunov theory. Finally, a numerical example is provided to validate the
theoretical results.
PMID- 28689701
TI - Surface Changes of PathFile after Glide Path Preparation: An Ex Vivo and In Vivo
Study.
AB - INTRODUCTION: The aim of this study was to evaluate the changes in the surface
profile of rotary nickel-titanium (NiTi) files designed to prepare a glide path
and conventional stainless steel (SS) hand files when used in extremely narrow
canals both in clinical and experimental conditions. METHODS: This ex vivo/in
vivo study used either SS #10 K hand files or the PathFile system (Dentsply
Maillefer, Ballaigues, Switzerland) to establish a glide path in maxillary molars
with narrow root canals (defined as canals that bound a #8 K-file at the working
length). After treatment, all files were cleaned and scanned using a noncontact
laser profilometer. Changes to the surface profile (Ra cutting edge waviness =
RaCEW) and roughness (Ra cutting edge roughness = RaCER) of the cutting edges and
the surface roughness of the flute area (Sa flute roughness = SaFR) were
analyzed. RESULTS: #10 K-files had significant increases in all types of
measurements (RaCEW, RaCEW, and SaFR) after the preparation of second mesiobuccal
canals compared with the control group (P < .05) in both studies. In the ex vivo
study, the PathFile (P1) had no significant changes in the surface profile from
baseline but had a significant increase in the surface roughness of the flute
(SaFR) (P < .05). PathFiles that were used 3 times in vivo had a significant
increase in roughness (flute and cutting edge) values across all PathFile sizes
compared with control values. CONCLUSIONS: This study showed that PathFiles had
significantly less surface defects compared with SS files after the preparation
of narrow canals, indicating their possible benefits when establishing a glide
path in extremely narrow canals.
PMID- 28689702
TI - Influence of Cone-beam Computed Tomography on Endodontic Retreatment Strategies
among General Dental Practitioners and Endodontists.
AB - INTRODUCTION: Treatment options for endodontic failure include nonsurgical or
surgical endodontic retreatment, intentional replantation, and extraction with or
without replacement of the tooth. The aim of the present study was to determine
the impact of cone-beam computed tomographic (CBCT) imaging on clinical decision
making among general dental practitioners and endodontists after failed root
canal treatment. A second objective was to assess the self-reported level of
difficulty in making a treatment choice before and after viewing a preoperative
CBCT scan. METHODS: Eight patients with endodontically treated teeth diagnosed as
symptomatic apical periodontitis, acute apical abscess, or chronic apical abscess
were selected. In the first session, the examiners were given the details of each
case, including any relevant radiographs, and were asked to choose 1 of the
proposed treatment alternatives and assess the difficulty of making a decision.
One month later, the examiners reviewed randomly the same 8 cases with the
additional information from the CBCT data. RESULTS: The examiners altered their
treatment plan after viewing the CBCT scan in 49.8% of the cases. A significant
difference in the treatment plan between the 2 imaging modalities was recorded
for endodontists and general practitioners (P < .05). After CBCT evaluation,
neither group altered their self-reported level of difficulty when choosing a
treatment plan (P = .0524). The extraction option rose significantly to 20% after
viewing the CBCT scan (P < .05). CONCLUSIONS: CBCT imaging directly influences
endodontic retreatment strategies among general dental practitioners and
endodontists.
PMID- 28689703
TI - To the G20: incentivising antibacterial research and development.
PMID- 28689704
TI - Glycated Hemoglobin, Albuminuria and Surrogate Markers of Macrovascular Disease
in Adults Without Diabetes: The Guangzhou Biobank Cohort Study, Cardiovascular
Disease Subcohort.
AB - OBJECTIVES: To explore the clinical utility of glycated hemoglobin (A1C) levels
as an early marker of albuminuria, macrovascular disease and subclinical
cardiovascular disease in comparison to fasting and postprandial glucose levels
in a well-characterized Chinese population with no history of diabetes. METHODS:
The study population consisted of 1223 individuals who were enrolled in the
Guangzhou Biobank Cohort Study, Cardiovascular Disease Subcohort, and who had
undergone oral glucose tolerance tests. The associations between each glycemic
measure and albuminuria, carotid intima-media thickness (CIMT) and CIMT-based
presence of carotid plaques and aortic arch calcification were assessed by chest
radiographs. RESULTS: The overall prevalence of albuminuria, carotid plaque and
any aortic arch calcification was 20.6%, 22.8% and 25.8%, respectively. All 3
glycemia indices were significantly associated with albuminuria, but only 1
(fasting glucose) was associated with carotid plaques. No significant difference
was detected among them in the area under the curve for albuminuria (chi-square
test; p=0.84), carotid plaques (p=0.28) or calcifications (p=0.29). In
sensitivity analysis, adjusted for age and sex, the above findings remained
unchanged. CONCLUSIONS: Although there was evidence suggesting differential
associations, the performance of the glycemic indices was similar, and their
association with macrovascular disease and albuminuria was modest.
PMID- 28689705
TI - Response to the Letter to the Editor From Dr. Kawada, "Depressive Symptoms,
Diabetes Distress and Serum Hemoglobin A1C in South Asians With Type 2 Diabetes
Mellitus Living in Canada".
PMID- 28689706
TI - The Innovative Canadian Pharmacogenomic Screening Initiative in Community
Pharmacy (ICANPIC) study.
AB - OBJECTIVES: The safety and efficacy of medications can vary significantly between
patients as a result of genetic variability. As genomic screening technologies
become more widely available, pharmacists are ideally suited to use such tools to
optimize medication therapy management. The objective of this study was to
evaluate the feasibility of implementing personalized medication services into
community pharmacy practice and to assess the number of drug therapy problems
identified as a result of pharmacogenomic screening. SETTING: The study was
conducted in 2 busy urban community pharmacies, operating under the brand
Shoppers Drug Mart, in Toronto, Ontario. PRACTICE INNOVATION: Pharmacists offered
pharmacogenomic screening as part of their professional services program.
Eligible patients received a buccal swab followed by DNA analysis with the use of
Pillcheck. Pillcheck is a genotyping assay that translates genomic data and
generates a personalized evidence-based report that provides insight into
patients' inherited drug metabolic profile. After receiving the report,
pharmacists invited patients back to the clinic for interpretation of the
results. Clinically significant drug therapy problems were identified and
recommendations for medication optimization forwarded to the primary care
physician. RESULTS: One hundred patients were enrolled in the study. Average age
was 56.7 years, and patients were taking a mean of 4.9 chronic medications.
Pharmacists cited the most common reasons for testing as ineffective therapy
(43.0%), to address an adverse reaction (32.6%), and to guide initiation of
therapy (10.4%). An average of 1.3 drug therapy problems directly related to
pharmacogenomic testing were identified per patient. Pharmacist recommendations
included change in therapy (60.3%), dose adjustment (13.2%), discontinuation of a
drug (4.4%), and increased monitoring (22.1%). CONCLUSION: These results
highlight the readiness of community pharmacists to adopt pharmacogenomic
screening into practice and their ability to leverage this novel technology to
positively affect medication therapy management. Community pharmacists are
ideally suited to both offer personalized medication services and interpret
genomic results.
PMID- 28689707
TI - Any questions? Yes, do pharmacists monitor medications at refill?
AB - OBJECTIVES: To describe pharmacists' self-reported refill monitoring activities
and test for demographic and work setting differences that contribute to
variation. METHODS: This study used a cross-sectional survey design. A 4-contact
survey was mailed to 599 community pharmacists randomly selected from a list
provided by the state board of pharmacy. Surveys were mailed in June and July
2013. Descriptive statistics and analysis of variance were used to characterize
these data. RESULTS: Of the 599 surveys mailed, 269 complete responses were
received for a 44.9% response rate. Pharmacists reported reviewing the patient's
medication profile for 40% of refills. Of the 29% of refills handed off,
pharmacists asked 70% of patients if they had any questions and 23% a specific
question about drug therapy. Pharmacists at mass merchandisers and those in
smaller towns were least likely to examine the profile, whereas pharmacists
working at independent stores, owners, and pharmacists with a BS Pharm degree
were most likely to hand off refills to patients. Demographic and work-setting
characteristics factors were not associated with the rate of asking specific
questions about the patient's drug therapy, although pharmacists with a BS Pharm,
at an independent store, or working in the smallest towns were least likely to
ask "Any questions?" when handing off the prescription. CONCLUSION: Pharmacists
reported reviewing patient profiles, handing off prescriptions, and asking
medication-specific questions to fewer than one-half of patients picking up
refills. Pharmacists were more likely to inquire if patients had any questions
than to ask specific questions, and other researchers have reported that the
former phrasing may inadvertently serve to reduce patient engagement.
PMID- 28689708
TI - The growing role of biologics and biosimilars in the United States: Perspectives
from the APhA Biologics and Biosimilars Stakeholder Conference.
AB - OBJECTIVES: The American Pharmacists Association (APhA) convened the Biologics
and Biosimilars Stakeholder Conference on November 30, 2016, in Washington DC.
The objectives of the Conference were to determine the key issues and challenges
within the marketplace for biologics, follow-on biologics (FOBs), and
biosimilars, identify potential roles and responsibilities of pharmacists
regarding biologic and biosimilar medications, and identify actions or activities
that pharmacists may take to optimize the safe and cost-effective use of
biologics and biosimilars. DATA SOURCES: National thought leaders and stakeholder
representatives, including individuals from the Food and Drug Administration,
Centers for Medicare and Medicaid Services, a private third-party payer,
manufacturers, and several national organizations of health care professionals,
participated in the conference. Information shared by this group was supplemented
with relevant legal and regulatory information and published literature. SUMMARY:
Biologics play a valuable role in the treatment of numerous health conditions,
but their associated costs, which tend to be greater than those of small-molecule
drugs, place a burden on the health care system. Biosimilars (both
noninterchangeable and interchangeable) are highly similar copies of the
originator biologic and offer the potential to reduce costs and improve patient
access to biological products by increasing treatment options and creating a more
competitive market. Despite the potential benefits of biosimilars, certain
factors may limit their uptake. The conference participants explored issues that
different stakeholders think influence the use of biologics, including
biosimilars, in the United States. Barriers included technology, prescriber
pharmacist communication, legislation and regulations, limited patient and health
care practitioner knowledge of biological products, patient and health care
practitioner perceptions of biosimilars, and evolving science or lack of long
term data. After participants identified issues, they discussed strategies to
address these concerns, including the need to enhance the education of
pharmacists, prescribers, and patients regarding biologic products, including
biosimilars and FOBs; the passage of state laws and regulations that do not
impede the use of biosimilars, including interchangeable biosimilars; the use of
product-specific tracking information in electronic health records and
surveillance systems; bidirectional communication among pharmacists, prescribers,
and other members of the care team to support pharmacovigilance and the
maintenance of accurate patient records; and the development of evidence-based
third-party payer policies. CONCLUSION: Patient access to safe and cost-effective
treatments is an important goal for the health care system. As the availability
and use of biosimilars, including those determined to be interchangeable,
increases, their potential to lower costs and improve patient access to treatment
grows. However, the extent of such growth is, in part, dependent on various
stakeholders' decisions to provide, pay for, or use these products in a safe and
thoughtful manner. Ongoing stakeholder collaboration, educational activities, and
review of current government or payer policies are required to optimize the
uptake of biological products, including biosimilars.
PMID- 28689709
TI - The reliability of short-term measurement of heart rate variability during
spontaneous breathing in people with chronic obstructive pulmonary disease.
AB - BACKGROUND: Reduced heart rate variability (HRV), a marker of autonomic system
dysfunction, has been reported in patients with chronic obstructive pulmonary
disease (COPD). Yet, limited data exists on the reliability of HRV measurement in
this population. Here we investigated the reliability of short-term HRV
measurement performed during spontaneous breathing in patients with COPD.
METHODS: Thirteen individuals (8 males) with moderate-to-severe COPD (FEV1 46+/
16% predicted; FEV1/FVC 49+/-13) underwent standard time and frequency domain HRV
measurements derived from 5-minute electrocardiograms collected on two separate
days using a SphygmoCor device. Absolute and relative reliability was assessed by
a number of coefficients including within-subject random variation, systematic
change in the mean, and retest correlations. RESULTS: Within-subject coefficients
of variation (CV) ranged from 4.3% to 193.4%. The intraclass correlation
coefficients (ICCs) ranged from 0.72 to 0.93 for parameters related to overall
HRV, and from 0.57 to 0.59 for those related to parasympathetic tone in both time
and frequency domains. Mean heart rate was the only parameter that showed
excellent absolute and relative reliability (CV=4.3%, ICC=0.93). CONCLUSION: The
HRV measurements showed overall moderate-to-substantial reliability during
spontaneous breathing in COPD population. Our findings support the use of HRV
parameters for diagnosis and cardiac risk assessment, but only mean heart rate
can be used reliably for monitoring changes in autonomic status following
rehabilitation intervention in this population.
PMID- 28689710
TI - Colder is better: The differential effects of thermal acclimation on life history
parameters in a parasitoid fly.
AB - In this article, we assessed the effect of the rearing temperature on life
history traits of the poorly known fly Phasmovora phasmophagae (Diptera:
Tachinidae), a parasitoid of Agathemera crassa (Phasmatodea: Agathemeridae) in
order to: i) test the effect of ambient temperature on life history traits and
ii) assess the potential trade-off between reproduction and survival. Parasitoids
were obtained from a population of hosts located in the Andes range of central
Chile. Upon emergence from the host parasitoids were randomly allocated to three
thermal treatments (15 degrees C, 22.5 degrees C and 30 degrees C) and several
life history traits were measured. We recorded higher survival at 15 degrees C
and 22.5 degrees C and a lower survival at 30 degrees C.We found differences for
both body mass and head width among thermal treatments. In females, body mass was
higher at 15 degrees C than at 30 degrees C. An effect of breeding temperature
and sex was observed only for developmental time. In addition, males reared at
different temperatures during the pupal stage and held as adults at 22.5 degrees
C, exhibited no differences in longevity between treatments. A significant effect
of temperature on the mass of ovaries and lipid was recorded in females. These
patterns suggest a trade-off between reproduction and survival. Overall, data
seem to support the "colder is better" hypothesis, because Andean parasitoid P.
phasmophagae inhabiting and experimentally reared in colder environments have a
higher performance in all environments.
PMID- 28689711
TI - Differential expression of stress candidate genes for thermal tolerance in the
sea urchin Loxechinus albus.
AB - Marine ectotherms inhabiting intertidal and shallow subtidal environments are
continuously exposed to diurnal tidal cycles and seasonal variability in
temperature. These organisms have adaptive mechanisms to maintain cellular
homeostasis, irrespective of thermal environmental variation. In this study, we
describe the molecular responses to thermal stress in the edible sea urchin
Loxechinus albus. In particular, we determined the differential expression of a
set of molecular markers that have been identified as targets of stress-related
responses. These include the heat shock proteins (hsp70 and hsp90), cell
detoxification proteins (cytochrome P450), and osmorregulatory proteins (alpha
and beta - Na+/K+ATPase). We exposed individuals to different temperatures; a
warm treatment (18+/-1.0 degrees C), a cold treatment (10+/-1.0 degrees C), and a
control treatment (average local temperature of 14+/-1.0 degrees C) and
differential expression was quantified after 2, 6, 12 and 48h of exposure. Levels
of mRNA were quantified by reverse transcription-quantitative polymerase chain
reaction, and the relative expression of each gene was calculated using the 18S
rRNA gene as a reference, and the control treatment as a calibrator. We found
that the expression levels of all studied genes increased during exposure to
warmth. The largest increase in expression was observed in cytochrome p450 genes
(ca. sixteen-fold); this was followed by increases in the expression of the
Na+/K+ATPase (ca. eight-fold) and by the hsp (ca. six fold) genes. These results
indicate that sea urchin thermal stress responses depend on differential gene
regulation, involving heat-shock, membrane potential, and detoxification genes
that generate an integrated adaptive response to acute environmental changes.
PMID- 28689712
TI - Effects of increasing temperature on antioxidant defense system and oxidative
stress parameters in the Antarctic fish Notothenia coriiceps and Notothenia
rossii.
AB - Antioxidant defense system (ADS) and oxidative stress parameters were evaluated
in the Antarctic fish Notothenia rossii and N. coriiceps exposed to increasing
temperature. Acclimated fish were kept at 0 degrees C or exposed to 4 degrees C
for 1day (N. rossii) or to 2 and 4 degrees C for 1 and 6 days (N. coriiceps).
Measurements were assessed in brain, gills, liver, white muscle and erythrocytes.
Parameters analyzed included antioxidant capacity against peroxyl radicals
(ACAP); reduced glutathione (GSH) and metallothionein-like proteins (MTLP)
concentration; superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase
(GPx), glutathione-S-transferase (GST) and glutamate-cysteine ligase (GCL)
activity; lipid peroxidation (LPO) level and protein carbonyl (PC) concentration.
Increased liver GST activity was observed in N. rossii exposed to 4 degrees C for
1day. Increased muscle GPx activity was observed in N. coriiceps after exposure
to 2 degrees C for 1day. Reduced gill GPx activity and increased liver SOD
activity were observed after exposure to 4 degrees C for 1day. In N. coriiceps,
increased gill GCL activity and reduced gill GPx activity, as well as reduced
liver MTLP were observed after exposure to 2 degrees C for 6 days. Reduced brain
SOD activity and increased brain LPO; reduced gill ACAP, GSH concentration and
GPx activity, as well as increased gill GCL activity; reduced liver ACAP, MTLP,
SOD activity, GST activity and increased liver and erythrocytes LPO were observed
after exposure to 4 degrees C for 6 days. These findings indicate that ADS is
more responsive to short-term increasing temperature in the sluggish N. coriiceps
than in the active N. rossii. However, responses of N. coriiceps to long-term
increasing temperature were transient and did not prevent tissue oxidative
damage. Considering the predicted increase in temperature in the Southern Ocean
over the next decades, our findings suggest that Antarctic fishes are sensitive
to ocean warming, displaying tissue oxidative damage associated with the thermal
stress.
PMID- 28689713
TI - Antioxidant defense system and oxidative status in Antarctic fishes: The sluggish
rockcod Notothenia coriiceps versus the active marbled notothen Notothenia
rossii.
AB - Adaptive responses of antioxidant defense systems (ADS) to changes in increased
levels of activity are critical, especially in Antarctic fishes. The
benthopelagic marbled notothen (Notothenia rossii) shows higher spontaneous
activity than the benthonic and sluggish rockcod (N. coriiceps). Therefore, we
hypothesize that species-related responses of ADS would occur to counteract
different rates of reactive oxygen species formation in these two Antarctic fish.
Here we evaluated ADS and oxidative damage in tissues (brain, gills, liver and
white muscle) of the two Antarctic fish. Despite no significant differences in
lipid and protein oxidative damage were observed, we actually found species- and
tissue-specific differences in ADS. Gill metallothionein-like proteins (MTLP) and
liver reduced glutathione (GSH) concentrations were higher in N. coriiceps than
in N. rossii. Brain and gill antioxidant capacity against peroxyl radicals
(ACAP); gill enzyme [glutamate-cysteine ligase (GSL), superoxide dismutase (SOD)
and catalase (CAT)] activity; liver GCL and SOD activity; and white muscle CAT
activity were higher in N. rossii than in N. coriiceps. Therefore, the more
active fish (N. rossii) maintains higher activities of enzymes involved in
superoxide ions (O2.-) detoxification and GSH production in peripheral tissues
(gills, liver and white muscle). This allows the more active fish (N. rossii) to
keep levels of lipid and protein oxidative damage similar to those observed in
the sluggish fish (N. coriiceps). It is worth noting that the more active fish
also shows a higher brain antioxidant capacity, which could involve other non
enzymatic antioxidants like vitamins C and E. In contrast, N. coriiceps shows
lower consumption of non-enzymatic antioxidants in peripheral tissues than N.
coriiceps. As hypothesized, our results indicate that differences in ADS profiles
between fish species are likely related to their habits and metabolic rates. This
would imply in different fish abilities to deal with oxidative stress associated
with increasing seawater temperature.
PMID- 28689714
TI - Thermal stress in Danio rerio: a link between temperature, light, thermo-TRP
channels, and clock genes.
AB - It is believed that the biological systems perceiving temperature and light daily
cycles were subjected to the simultaneous selective pressures, which resulted in
their co-evolutionary association. We investigated the influence of 1h 33 degrees
C heat shock on the expression of clock and heat shock protein genes, as well as
the role of the thermo-TRP channel, TRPV1, in ZEM-2S cells of the teleost Danio
rerio, in constant dark (DD) or light-dark cycles (LD). After heat shock, we
observed an acute increase of hsp90 aa1 levels in both DD and LD conditions.
Interestingly, the expression of hsp90 aa1 was two-fold lower in LD than in DD,
what suggests an antagonistic effect of white light on heat shock action.
Regarding clock genes, no effect was found in cells subjected to the heat shock
in DD. When cells were kept in LD, the expression of per1, per2, cry1a, and cry1b
increased in response to heat shock, indicating that heat shock only affects
clock core of LD-synchronized ZEM-2S cells. We then evaluated whether TRPV1
played a role in heat-mediated hsp90 aa1 and per2 responses: hsp90 aa1 increase
was unaffected whereas per2 increase was partially blocked by TRPV1 inhibitor,
demonstrating the channel participation in clock gene regulation by heat shock.
Taken together, our results open a novel investigative perspective regarding the
relationship between temperature and clock genes, placing a new player in the
regulation of this phenomenon: the TRPV1 channel.
PMID- 28689715
TI - Exploration of low temperature microRNA function in an anoxia tolerant vertebrate
ectotherm, the red eared slider turtle (Trachemys scripta elegans).
AB - As a model for vertebrate long-term survival in oxygen-restricted environments,
the red-eared slider turtle (Trachemys scripta elegans) can adapt at the
biochemical level to survive in oxygen-free (anoxic) cold water (<10 degrees C).
This impressive ability is enabled through a coordinated suppression of energy
expensive, non-essential, cell processes. This study explored the anoxia
responsive expression of several microRNA species (miR-1a, -133, -17, -107,
148a, -21, -103, -210, -20a, -365 and -29b) in adult turtles exposed to 5h and
20h anoxia (at 5+/-1 degrees C). Furthermore, since microRNA target binding is
regularly defined only by microRNA-mRNA interactions at 37 degrees C, the
possibility of unique low temperature-selective microRNA targeting interactions
with mRNA was explored in this ectotherm. Approximately twice as many microRNA
mRNA interactions were predicted at 5 degrees C versus 37 degrees C with
particular enrichment of mRNA targets involved in biological processes known to
be part of the stress response. Hence, the results suggest that the influence of
temperature should be considered for the prediction of microRNA targets (and
their follow-up) in poikilothermic animals and that interacting effects of low
body temperature and anoxia on microRNA expression could potentially be important
to achieve the profound metabolic rate depression that characterizes turtle
hibernation underwater during the winter.
PMID- 28689716
TI - Exploring physiological plasticity and local thermal adaptation in an intertidal
crab along a latitudinal cline.
AB - Intertidal organisms have evolved physiological mechanisms that enable them to
maintain performance and survive during periods of severe environmental stress
with temperatures close to their tolerance limits. The level of these adaptive
responses in thermal physiology can vary among populations of broadly distributed
species depending on their particular environmental context and genetic
backgrounds. Here we examined thermal performances and reaction norms for
metabolic rate (MR) and heart rate (HR) of seven populations of the porcelanid
crab Petrolisthes violaceus from markedly different thermal environments across
the latitudinal gradient of ~3000km. Physiological responses of this intertidal
crab under common-garden conditions suggest the absence of local thermal
adaptation along the geographic gradient (i.e., lack of latitudinal
compensation). Moreover, thermal physiological sensitivities and performances in
response to increased temperatures evidenced the existence of some level of: i)
metabolic rate control or depression during warm temperature exposures; and ii)
homeostasis/canalization (i.e., absence or low levels of plasticity) in
physiological traits that may reflect some sort of buffering mechanism in most of
the populations. Nevertheless, our results indicate that elevated temperatures
can reduce cardiac function but not metabolic rate in high latitude crabs. The
lack of congruence between HR and MR supports the idea that energy metabolism in
marine invertebrates cannot be inferred from HR and different conclusions
regarding geographic differentiation in energy metabolism can be obtained from
both physiological traits. Integrating thermal physiology and species range
extent can contribute to a better understanding of the likely effects of climate
change on natural populations of marine ectotherms.
PMID- 28689717
TI - Compensation of thermal constraints along a natural environmental gradient in a
Malagasy iguanid lizard (Oplurus quadrimaculatus).
AB - Physiological or behavioural adjustments are a prerequisite for ectotherms to
cope with different thermal environments. One of the world's steepest
environmental gradients in temperature and precipitation can be found in
southeastern Madagascar. This unique gradient allowed us to study the
compensation of thermal constraints in the heliothermic lizard Oplurus
quadrimaculatus on a very small geographic scale. The lizard occurs from hot
spiny forest to intermediate gallery and transitional forest to cooler rain
forest and we investigated whether these habitat differences are compensated
behaviourally or physiologically. To study activity skin temperature (as proxy
for body temperature) and the activity time of lizards, we attached temperature
loggers to individuals in three different habitats. In addition, we calculated
field resting costs from field resting metabolic rate to compare energy
expenditure along the environmental gradient. We found no variation in activity
skin temperature, despite significant differences in operative environmental
temperature among habitats. However, daily activity time and field resting costs
were reduced by 35% and 28% in the cool rain forest compared to the hot spiny
forest. Our study shows that O. quadrimaculatus relies on behavioural mechanisms
rather than physiological adjustments to compensate thermal differences between
habitats. Furthermore, its foraging activity in open, sun exposed habitats
facilitates such a highly effective thermoregulation that cold operative
temperature, not energetically expensive heat, presents a greater challenge for
these lizards despite living in a hot environment.
PMID- 28689718
TI - Long-term and acute effects of temperature and oxygen on metabolism, food intake,
growth and heat tolerance in a freshwater gastropod.
AB - Temperature affects the physiology and life-history of ectothermic animals, often
increasing metabolic rate and decreasing body size. Oxygen limitation has been
put forward as a mechanism to explain thermal responses of body size and the
ability to survive stress. However the time-scales involved in growth performance
and heat tolerance differ radically. In order to increase our understanding of
oxygen and temperature effects on body size and heat tolerance and the time scale
involved, we reared Lymnaea stagnalis under six combinations of temperature and
oxygen tension from hatching up to an age of 300 days and recorded shell length
during this whole period. At the end of this period, we determined scope for
growth by measuring food intake rate, assimilation efficiency, respiration rate
and ammonium excretion rate at two different temperatures. We also measured the
snails' ability to survive heat stress (CTmax), both at normoxia and hypoxia. We
found that scope for growth and long term growth performance were much more
affected by interactions of chronic oxygen and temperature conditions during
rearing than by acute conditions during testing. Furthermore, our study shows
that individual variation in growth performance can be traced back to individual
differences in rates of food and oxygen consumption. Developmental acclimation
also gave rise to differences in CTmax, but these were relatively small and were
only expressed when CTmax was tested under hypoxia. The large effects of rearing
oxygen conditions on growth and other physiological rates compared to modest
effects of test oxygen conditions on CTmax suggest that small effects of hypoxia
on the short term (e.g. heat tolerance) may nevertheless have large repercussions
on the long term (e.g. growth and reproduction), even in a pulmonate snail that
can compensate for hypoxia to some extent by aerial respiration.
PMID- 28689719
TI - The thermal environment of the nest affects body and cell size in the solitary
red mason bee (Osmia bicornis L.).
AB - Many ectotherms grow larger at lower temperatures than at higher temperatures.
This pattern, known as the temperature-size rule, is often accompanied by plastic
changes in cell size, which can mechanistically explain the thermal dependence of
body size. However, the theory predicts that thermal plasticity in cell size has
adaptive value for ectotherms because there are different optimal cell-membrane
to-cell-volume ratios at different temperatures. At high temperatures, the demand
for oxygen is high; therefore, a large membrane surface of small cells is
beneficial because it allows high rates of oxygen transport into the cell. The
metabolic costs of maintaining membranes become more important at low
temperatures than at high temperatures, which favours large cells. In a field
experiment, we manipulated the thermal conditions inside nests of the red mason
bee, a solitary bee that does not regulate the temperature in its nests and whose
larvae develop under ambient conditions. We assessed the effect of temperature on
body mass and ommatidia size (our proxy of cell size). The body and cell sizes
decreased in response to a higher mean temperature and greater temperature
fluctuations. This finding is in accordance with predictions of the temperature
size rule and optimal cell size theory and suggests that both the mean
temperature and the magnitude of temperature fluctuations are important for
determining body and cell sizes. Additionally, we observed that males of the red
mason bee tend to have larger ommatidia in relation to their body mass than
females, which might play an important role during mating flight.
PMID- 28689720
TI - Thermal acclimation in American alligators: Effects of temperature regime on
growth rate, mitochondrial function, and membrane composition.
AB - We investigated the ability of juvenile American alligators (Alligator
mississippiensis) to acclimate to temperature with respect to growth rate. We
hypothesized that alligators would acclimate to cold temperature by increasing
the metabolic capacity of skeletal muscles and the heart. Additionally, we
hypothesized that lipid membranes in the thigh muscle and liver would respond to
low temperature, either to maintain fluidity (via increased unsaturation) or to
maintain enzyme reaction rates (via increased docosahexaenoic acid). Alligators
were assigned to one of 3 temperature regimes beginning at 9 mo of age: constant
warm (30 degrees C), constant cold (20 degrees C), and daily cycling for 12h at
each temperature. Growth rate over the following 7 mo was highest in the cycling
group, which we suggest occurred via high digestive function or feeding activity
during warm periods and energy-saving during cold periods. The warm group also
grew faster than the cold group. Heart and liver masses were proportional to body
mass, while kidney was proportionately larger in the cold group compared to the
warm animals. Whole-animal metabolic rate was higher in the warm and cycling
groups compared to the cold group - even when controlling for body mass - when
assayed at 30 degrees C, but not at 20 degrees C. Mitochondrial oxidative
phosphorylation capacity in permeabilized fibers of thigh muscle and heart did
not differ among treatments. Membrane fatty acid composition of the brain was
largely unaffected by temperature treatment, but adjustments were made in the
phospholipid headgroup composition that are consistent with homeoviscous
adaptation. Thigh muscle cell membranes had elevated polyunsaturated fatty acids
in the cold group relative to the cycling group, but this was not the case for
thigh muscle mitochondrial membranes. Liver mitochondria from cold alligators had
elevated docosahexaenoic acid, which might be important for maintenance of
reaction rates of membrane-bound enzymes.
PMID- 28689721
TI - Studying the evolutionary significance of thermal adaptation in ectotherms: The
diversification of amphibians' energetics.
AB - A fundamental problem in evolutionary biology is the understanding of the factors
that promote or constrain adaptive evolution, and assessing the role of natural
selection in this process. Here, comparative phylogenetics, that is, using
phylogenetic information and traits to infer evolutionary processes has been a
major paradigm . In this study, we discuss Ornstein-Uhlenbeck models (OU) in the
context of thermal adaptation in ectotherms. We specifically applied this
approach to study amphibians's evolution and energy metabolism. It has been
hypothesized that amphibians exploit adaptive zones characterized by low energy
expenditure, which generate specific predictions in terms of the patterns of
diversification in standard metabolic rate (SMR). We complied whole-animal
metabolic rates for 122 species of amphibians, and adjusted several models of
diversification. According to the adaptive zone hypothesis, we expected: (1) to
find "accelerated evolution" in SMR (i.e., diversification above Brownian Motion
expectations, BM), (2) that a model assuming evolutionary optima (i.e., an OU
model) fits better than a white-noise model and (3) that a model assuming
multiple optima (according to the three amphibians's orders) fits better than a
model assuming a single optimum. As predicted, we found that the diversification
of SMR occurred most of the time, above BM expectations. Also, we found that a
model assuming an optimum explained the data in a better way than a white-noise
model. However, we did not find evidence that an OU model with multiple optima
fits the data better, suggesting a single optimum in SMR for Anura, Caudata and
Gymnophiona. These results show how comparative phylogenetics could be applied
for testing adaptive hypotheses regarding history and physiological performance
in ectotherms.
PMID- 28689722
TI - Genetic components in a thermal developmental plasticity of the beetle Tribolium
castaneum.
AB - Low developmental temperatures cause ectotherms to retard growth, postpone
maturation, and emerge at either larger or smaller adult size. In this study, we
explored how these thermal responses evolved, focusing on their genetic basis. We
applied a full diallel breeding design on inbred lines of the flour beetle,
Tribolium castaneum. To assess the proportional contributions of genetic and non
genetic effects, each genotype, a unique combination of parental haplotypes, was
reared from an egg to imago at five developmental temperatures. Faster
development of females vs. males was associated with comparatively larger body
masses of females (pupae and imago). In contrast, the rapid development caused by
warmer environments resulted in smaller beetles (pupae and imago), but there were
significant differences in this trait among genotypes. Independent effects of
parental haplotypes played the major role in explaining the variance of body
mass, but interactive effects of parental haplotypes explained most of the
variance in developmental length. Genotypes responded to the thermal environment
in a markedly uniform way. Nevertheless, we found the low statistically
significant variance in the slopes of thermal reaction norms for body mass and
developmental, which was mainly driven by the interactive effects of parental
haplotypes. Overall, the thermal plasticity of T. castaneum follows the most
common pattern among ectotherms, the so-called temperature-size rule. Detection
of the low genetic variance in the shape of this response supports the idea that
thermal developmental plasticity remains under a strong selective pressure in
ectotherms.
PMID- 28689723
TI - Methods and pitfalls of measuring thermal preference and tolerance in lizards.
AB - Understanding methodological and biological sources of bias during the
measurement of thermal parameters is essential for the advancement of thermal
biology. For more than a century, studies on lizards have deepened our
understanding of thermal ecophysiology, employing multiple methods to measure
thermal preferences and tolerances. We reviewed 129 articles concerned with
measuring preferred body temperature (PBT), voluntary thermal tolerance, and
critical temperatures of lizards to offer: a) an overview of the methods used to
measure and report these parameters, b) a summary of the methodological and
biological factors affecting thermal preference and tolerance, c) recommendations
to avoid identified pitfalls, and d) directions for continued progress in our
application and understanding of these thermal parameters. We emphasize the need
for more methodological and comparative studies. Lastly, we urge researchers to
provide more detailed methodological descriptions and suggest ways to make their
raw data more informative to increase the utility of thermal biology studies.
PMID- 28689724
TI - Thermal biology in two syntopic lizards, Phymaturus extrilidus and Liolaemus
parvus, in the Puna region of Argentina.
AB - Body temperature is the most important ecophysiological variable affecting
reptiles' life history. Moreover, thermoregulation in ectotherms implies a
struggle to reach preferred temperatures in natural conditions due to the
influence of biotic and abiotic factors. Our objective was to evaluate and
compare the thermal biology of two syntopic species, Phymaturus extrilidus and
Liolaemus parvus, in the Puna region of San Juan, Argentina. We determined body
temperature (Tb), micro-environmental temperatures (Ta and Ts) and operative
temperatures (Te) in the field. In the laboratory, we measured preferred
temperatures (Tpref) and calculated the index of thermoregulatory efficiency (E).
Neither body temperatures in the field nor preferred temperatures varied between
seasons and sexes. Body temperatures were lower than preferred temperatures for
both species. Nevertheless, regardless of the low thermal offer available in
habitat, both species did achieve body temperatures higher than operative
temperatures during activity. Thermoregulatory effectiveness was moderate in P.
extrilidus (E=0.65), while L. parvus presented greater thermoregulatory
efficiency (E=0.78). We conclude that under the rigorous climate conditions of
the Puna, Phymaturus extrilidus and Liolaemus parvus are able to actively and
efficiently thermoregulate, maintaining body temperatures close to the preferred
and higher than those of its habitat. Differences in thermal characteristics
between Phymaturus extrilidus and Liolaemus parvus are a consequence of
differential limitations imposed on each species by the environment and of forces
inherent to their life histories.
PMID- 28689725
TI - Phylogenetic analysis of the allometry of metabolic rate and mitochondrial basal
proton leak.
AB - The mitochondrial basal proton leak (MBPL) significantly contributes to high body
temperatures (Tb) and basal metabolic rates (BMR) in endotherms. In endotherms at
a given body mass (M), liver MBPL is higher than in ectotherms, supporting the
notion that MBPL may partly explain the evolutionary increase in metabolic rate
(MR), fostering endothermy. Here, we re-addressed this assumption by performing a
phylogenetic analysis comparing all available liver MBPL data for ecto- and
endotherms. While MBPL within endotherms negatively scales with M and BMR as
shown previously, MBPL of ectotherms does not scale allometrically with M.
Phylogenetic analysis reveals that this result is confounded by a positive
scaling coefficient for MBPL with M for reptiles. Strikingly, the reptilian MBPL
reaches endothermic levels above a body mass of 6.6kg. Thus, phylogenetic scaling
of MBPL supports previous claims of endotherm-like physiological characteristics
in large reptiles. It appears that diversification of ancestral ectothermic
tetrapods to a body mass of at least 6kg may have been required to reach a MBPL
that is beneficial for sustained high body temperatures. Novel MBPL data for the
lesser hedgehog tenrec, a protoendothermic eutherian that displays reptile-like
thermoregulatory patterns, fall within the endo- and ectothermic allometric
regressions. Finally, we add additional evidence that within endotherms,
phylogenetic differences in MR do not correlate with MBPL. Collectively, these
data suggest that MBPL does not universally scale with metabolic rate in ecto- or
endotherms and that an increasing MBPL with M may have played an important
physiological role in the evolutionary history of reptilian thermoregulation.
PMID- 28689726
TI - Physical mechanism or evolutionary trade-off? Factors dictating the relationship
between metabolic rate and ambient temperature in carabid beetles.
AB - The tight association between ambient temperature (T) and metabolic rate (MR) is
a common occurrence in ectotherms, but the determinants of this association are
not fully understood. This study examined whether the relationship between MR and
T is the same among individuals, as predicted by the Universal Temperature
Dependence hypothesis, or whether this relationship differs between them. We used
flow-through respirometry to measure standard MR and to determine gas exchange
patterns for 111 individuals of three Carabidae species which differ in size
(Abax ovalis, Carabus linnei and C. coriaceus), exposed to four different
temperatures (ten individuals of each species measured at 6, 11, 16 and 21
degrees C). We found a significant interaction between ln body mass and the
inverse of temperature, indicating that in a given species, the effect of
temperature on MR was weaker in larger individuals than in smaller individuals.
Overall, this finding shows that the thermal dependence of MR is not body mass
invariant. We observed three types of gas exchange patterns among beetles:
discontinuous, cyclic and continuous. Additionally, the appearance of these
patterns was associated with MR and T. Evolution in diverse terrestrial
environments could affect diverse ventilation patterns, which accommodate changes
in metabolism in response to temperature variation. In conclusion, explaining the
variance in metabolism only through fundamental physical laws of thermodynamics,
as predicted by the Universal Temperature Dependence hypothesis, appears to
oversimplify the complexity of nature, ignoring evolutionary trade-offs that
should be taken into account in the temperature - metabolism relationship.
PMID- 28689727
TI - Temperature stress and insect immunity.
AB - This mini-review summarizes the recent knowledge concerning the role of
temperature in the immune response of insects. The heat-shock is described as a
common phenomenon in both homotherms and poikilotherms, and the role of heat
shock proteins in innate immunity is recalled taking into account its
evolutionary aspects. Similar to homothermic animals, which show a febrile
reaction to infection, poikilothermic invertebrates such as insects develop
behavioural fever as part of their immune response. It can be elicited not only
by the presence of the pathogen itself but also by injection of immune
stimulators i.e. components of the microbial cell wall. In analogy to fever in
homotherms, this process seems to be regulated by the prostaglandin/eicosanoid
biosynthesis pathway. The positive effects of temperature change on insect
immunity are presented in the paper.
PMID- 28689728
TI - Enablers towards establishing and growing South Africa's waste to electricity
industry.
AB - In South Africa the electricity generation mix is relatively un-diverse whereas
globally the transformation of the sector is advancing rapidly. Coal remains the
predominant fuel source and limited success has to date been achieved in the
renewable energy sector. The electricity generation sector is therefore hindered
from moving towards an electricity generation landscape where alternative fuel
sources is utilised. This research is aimed at gaining insight into the enablers
that led towards an increasing trend (observed globally) in exploiting waste as a
fuel for electricity generation, and to outline the presence of obstacles that
hinder separation of waste for electricity use in the South African context.
Furthermore it is an attempt at informing what appropriate interventions
(operational and policy) may be considered suitable for South Africa to overcome
these barriers in order to enable a sustainable South African waste to
electricity (WTE) Industry. Findings show that numerous barriers to a WTE exists
in the South African context, however overcoming these barriers is not as simple
as adopting the European model with the aim to modify the electricity generation
mix and waste management landscape. Selected enablers deemed appropriate in the
South African context are adapted from the European model, and are greatly
influenced by the prevailing socio-economic status of South Africa. Primary
enablers identified were, (i) government support is needed especially in the form
of subsidisation for green energy, (ii) increase landfill costs through the
implementation of a landfill tax, (iii) streamline the process for Independent
Private Power Producers (IPPPs) to connect to the national grid with off-take
guaranteed and the inclusion of WTE into an electricity roadmap (effectively
government's strategy). The proposed enabling interventions would help in
overcoming the barriers for a South African WTE industry.
PMID- 28689729
TI - TRPML1: The Ca(2+)retaker of the lysosome.
AB - Efficient functioning of lysosome is necessary to ensure the correct performance
of a variety of intracellular processes such as degradation of cargoes coming
from the endocytic and autophagic pathways, recycling of organelles, and
signaling mechanisms involved in cellular adaptation to nutrient availability.
Mutations in lysosomal genes lead to more than 50 lysosomal storage disorders
(LSDs). Among them, mutations in the gene encoding TRPML1 (MCOLN1) cause
Mucolipidosis type IV (MLIV), a recessive LSD characterized by neurodegeneration,
psychomotor retardation, ophthalmologic defects and achlorhydria. At the cellular
level, MLIV patient fibroblasts show enlargement and engulfment of the late endo
lysosomal compartment, autophagy impairment, and accumulation of lipids and
glycosaminoglycans. TRPML1 is the most extensively studied member of a small
family of genes that also includes TRPML2 and TRPML3, and it has been found to
participate in vesicular trafficking, lipid and ion homeostasis, and autophagy.
In this review we will provide an update on the latest and more novel findings
related to the functions of TRPMLs, with particular focus on the emerging role of
TRPML1 and lysosomal calcium signaling in autophagy. Moreover, we will also
discuss new potential therapeutic approaches for MLIV and LSDs based on the
modulation of TRPML1-mediated signaling.
PMID- 28689730
TI - Feasibility of Endo GIATM Reinforced Reload with Tri-StapleTM Technology for
delta-shaped anastomosis.
AB - BACKGROUND: We report the short-term clinical outcomes of a delta-shaped (DS)
anastomosis in laparoscopic distal gastrectomy (LDG), comparing Endo GIATM
Reinforced Reload (Reinforced GIA) with Endo GIATM (GIA) staplers. METHODS: This
was a retrospective analysis of 40 patients who underwent totally LDG with DS
anastomosis with Reinforced GIA (group A) and 90 patients who underwent the same
procedure with GIA (group B) for clinical T1-T3 gastric cancer from May 2013 to
December 2016. Operation time, intraoperative blood loss, hospital length of
stay, reconstruction time, and complications were compared. RESULTS: No patients
required conversion to open surgery, and no patients died. There was no
significant difference between the groups regarding patient background,
postoperative hospital stay, and operation time. Bleeding from the V-shaped
anastomosis was significantly less frequent in group A compared with group B (0%
vs 11.2%, p = 0.021). Anastomosis-related complications were less frequent in
group A, but there was no statistically significant difference between the
groups. The fasting period in group A was significantly shorter than that of
group B (2.81 vs 3.39 days, p = 0.034). CONCLUSION: DS anastomosis using
Reinforced GIA can prevent minor postoperative anastomosis leakage. Based on our
findings and experience, we recommend DS anastomosis with Reinforced GIA after
LDG for gastric cancer as an effective procedure with good short-term outcomes.
PMID- 28689731
TI - Surgical management of primary hyperparathyroidism: A single-center experience.
AB - BACKGROUND: Primary hyperparathyroidism (PHPT) can occur at any age. This study
aimed to compare the necessity, feasibility, safety, and outcomes of
parathyroidectomy in the management of minor-symptomatic or asymptomatic PHPT
patients according to age (young vs. old). METHODS: We retrospectively reviewed
the medical records of 146 consecutive patients who underwent surgery for PHPT
from January 2005 to June 2016 in our institution. The patients ranged in age
from 12 to 85 years. For the analysis, the included patients (n = 137) were
separated into young (age <50 years; n = 31, 22.6%) and old (age >=50 years; n =
106, 77.4%) patients. The biochemical characteristics (parathyroid hormone,
calcium, and creatinine levels), T-score of bone densitometry, surgical reports,
pathology reports, perioperative intensive care unit care, and 30-day mortality
were reviewed. RESULTS: The average medical treatment course after diagnosis
tended to be longer in the old group (33.3 vs. 26.2 weeks, p = 0.62). During the
medical treatment course, the old group had a higher risk of developing new
symptoms or severe complications (5.6% vs. 3.2%, p = 0.05), and the older
patients seemed to have a longer postoperative hospitalization (p = 0.17).
However, there were no significant differences in the 30-day mortality, immediate
complications, and follow-up duration. CONCLUSION: In older patients, surgical
treatment of PHPT is safe and feasible, with comparable outcomes to in younger
patients, and helps prevent the development or progression of symptoms and
complication. Hence, parathyroidectomy should be the recommended treatment and
should be performed in PHPT patients as early as possible, regardless their age
and initial symptoms.
PMID- 28689732
TI - Applying preoperative dipyridamole thallium-201 scintigraphy for preventing
cardiac mortality and complications for patients with secondary
hyperparathyroidism undergoing parathyroidectomy.
AB - BACKGROUND: To evaluate the value of preoperative dipyridamole thallium-201
scintigraphy for reducing cardiovascular complication in secondary
hyperparathyroidism (SHPTH) patients. METHODS: Thallium scintigraphy was arranged
for all dialysis patients who underwent parathyroidectomy from Jan 2011 to July
2015. Management of defects on thallium scintigraphy included cardiac
catheterization and ultrasonography. Analysis includes 30-day mortality,
morbidity and the predicting factors for thallium scintigraphy defect. RESULTS:
Of 249 patients with SHPTH, 19 (7.6%) had defects on thallium scintigraphy, 15
(88%) of whom had coronary artery disease on angiography. History of acute
coronary syndrome (ACS, p < 0.001), diabetes mellitus (DM, p = 0.03), male sex (p
= 0.03), and higher body mass index (BMI, p = 0.001) were significant predictors
of positive thallium scintigraphy results. History of ACS was the most
significant predictor after adjustment in the multivariate logistic analysis
(odds ratio, 22.56; 95% confidence interval, 7.02-72.53). All the patients
survived the 30-day postoperative period, with minimal cardiovascular morbidity.
CONCLUSION: Preoperative dipyridamole thallium-201 scintigraphy is useful for
SHPTH patients to minimized surgical mortality and morbidity.
PMID- 28689733
TI - Long-term outcome of laparoscopic sleeve gastrectomy from a single center in
mainland China.
AB - BACKGROUND/OBJECTIVE: Laparoscopic sleeve gastrectomy (LSG) is at present the
most popular bariatric procedure due to its significant weight loss, remission of
co-morbidities, and acceptable morbidity. But, there are not many studies showing
its long term efficacy and safety in Chinese patients. The aim of this study is
to give five results of LSG in terms of weight loss, co-morbidity (Type 2
diabetes mellitus) resolution and possible complications from a single center in
mainland China. MATERIAL AND METHODS: This is a retrospective study of 218 obese
patients who underwent LSG by a single surgeon from June 2011 to June 2016.
Patients were subjected to standardized perioperative evaluation and education
program. Patients were followed up after 1, 3, 6, 12, 18, and 24 months and
yearly thereafter. Long term outcomes in terms of weight loss in kg, % of total
weight loss (%TWL), % excess weight loss (%EWL), % resolution of type 2 diabetes
mellitus (T2DM) and % complication rate are studied. RESULTS: The %TWL was 33.8
+/- 5.9, 28.8 +/- 8.9, 26.6 +/- 6.9, 18.0 +/- 7.6, 15.0 +/- 7.1 and %EWL was 62.8
+/- 16.9 (n-96), 49.5 +/- 18.5 (n-43), 39.8 +/- 13.1 (n-15), 32.2 +/- 2.1 (n-13),
19.5 +/- 8.7 (n-2) at 1, 2, 3, 4 and 5 years, respectively. T2DM remission rate
was 72.9% at one year. There were no major complications like leak, stricture,
staple line bleeding, port site herniation and gastro-esophageal reflux disease
(GERD). There was no mortality. Most common early complication was port site
dehiscence (10%), managed conservatively; none requiring readmission. No
reoperation was done for weight regain. CONCLUSION: LSG is a safe and effective
procedure with good five year results. Weight regain remains a concern two years
post surgery. Standardization of LSG is important to reduce major complications.
PMID- 28689734
TI - Global prevalence of hypertension among people living with HIV: a systematic
review and meta-analysis.
AB - The purpose of this study was to estimate, through meta-analysis, the global
prevalence of hypertension among people living with HIV (PLWH). A total of 49
studies published during 2011-2016 with 63,554 participants were included in
analysis. These studies were conducted in America (25), Europe (13), Africa (10),
and Asia (1) with data collected during 1996-2014. Prevalence of hypertension and
confidence interval was estimated and stratified by participants' age,
antiretroviral therapy (ART), and calendar-years using random effects modeling.
The quality assessed using the Joanna Briggs Institute Prevalence Critical
Appraisal Tool was high for all included studies. The estimated prevalence (95%
confidence interval) of hypertension was 25.2% (21.2%, 29.6%) for the overall
sample, 34.7% (27.4%, 42.8%) for ART-experienced, and 12.7% (7.4%, 20.8%) for ART
naive participants. The estimated prevalence was found increased with age and in
studies conducted after 2010. Hypertension among PLWH shows an increasing trend
and is associated with receiving ART and older age. Findings of this study
provide data for decision makers to incorporate blood pressure assessment in
primary prevention and for researchers to further investigate factors and
mechanisms related to hypertension among PLWH.
PMID- 28689735
TI - Green to gray: Silicon Valley of India.
AB - Rapid growth, population concentration and the expansion of urban areas towards
peri-urban regions have led to changes in urban structure and composition, and
consequently changes in urban ecology. The purpose of this study is to estimate
trees in the urban environment through quantification of vegetation cover using
multi resolution spatial data supplemented with tree data acquired from field
using pre-calibrated GPS. Optimal resolution for extracting trees was attained
through fusion of multi resolution (spectral and spatial) data. Results highlight
region with spatial extent of 741 sq. km with 9.5 million human population has
about 1.48 million trees. Further, urban growth increment is expected to cover
95% of the landscape with paved surfaces by 2020 decreasing vegetation cover
while severely affecting the local ecology and environment in addition to human
survival.
PMID- 28689737
TI - Asymmetrically deployed actomyosin-based contractility generates a boundary
between developing leg segments in Drosophila.
AB - The formation of complex tissues from simple epithelial sheets requires the
regional subdivision of the developing tissue. This is initially accomplished by
a sequence of gene regulatory hierarchies that set up distinct fates within
adjacent territories, and rely on cross-regulatory interactions to do so.
However, once adjacent territories are established, cells that confront one
another across territorial boundaries must actively participate in maintaining
separation from each other. Classically, it was assumed that adhesive differences
would be a primary means of sorting cells to their respective territories. Yet it
is becoming clear that no single, simple mechanism is at play. In the few
instances studied, an emergent theme along developmental boundaries is the
generation of asymmetry in cell mechanical properties. The repertoire of ways in
which cells might establish and then put mechanical asymmetry to work is not
fully appreciated since only a few boundaries have been molecularly studied.
Here, we characterize once such boundary in the develop leg epithelium of
Drosophila. The region of the pretarsus / tarsus is a known gene expression
boundary that also exhibits a lineage restriction (Sakurai et al., 2007). We now
show that the interface comprising this boundary is strikingly aligned compared
to other cell interfaces across the disk. The boundary also exhibits an asymmetry
for both Myosin II accumulation as well as one of its activators, Rho Kinase.
Furthermore, the enrichment correlates with increased mechanical tension across
that interface, and that tension is Rho Kinase-dependent. Lastly, interfering
with actomyosin contractility, either by depletion of myosin heavy chain or
expression of a phosphomimetic variant of regulatory light chain causes defects
in alignment of the interfaces. These data suggest strongly that mechanical
asymmetries are key in establishing and maintaining this developmental boundary.
PMID- 28689738
TI - Unconjugated bile acids in rat brain: Analytical method based on LC/ESI-MS/MS
with chemical derivatization and estimation of their origin by comparison to
serum levels.
AB - Although some studies have revealed the implication of bile acids (BAs) and
neurological diseases, the levels and origin of the BAs in the brain are not
fully understood. In this study, we first developed and validated a sensitive and
specific method for the determination of three unconjugated BAs [cholic acid
(CA), chenodeoxycholic acid (CDCA) and deoxycholic acid (DCA)] in the rat brain
by liquid chromatography/electrospray ionization-tandem mass spectrometry
combined with chemical derivatization. The measured brain concentrations (mean+/
standard deviation, n=10) of normal rats were 58.7+/-48.8, 14.2+/-11.7 and 13.2+/
8.7ng/g tissue for CA, CDCA and DCA, respectively. For their origin, we developed
the hypothesis that they might be mostly derived from the periphery. To test this
hypothesis, the brain BA levels were compared with the serum levels. The brain
levels had high correlations with the serum levels, and were always lower than
the serum levels for the three unconjugated BAs. Furthermore, the higher brain-to
serum concentration ratios were found for the BAs with higher logD values (higher
lipophilicity). Moreover, the brains of the rats intraperitoneally administered
with deuterium-labeled CA and CDCA were also analyzed; the deuterium-labeled BAs
were detected in the brain of the rats administered with these compounds. Based
on all the results, we concluded that the BAs found in the brain are mostly
derived from the periphery and the major mechanism for the transportation of the
unconjugated BAs to the brain is by passive diffusion.
PMID- 28689739
TI - The Accidental Orthodoxy of Drs. Mueller and Hinton.
PMID- 28689736
TI - Zebrafish zic2 controls formation of periocular neural crest and choroid fissure
morphogenesis.
AB - The vertebrate retina develops in close proximity to the forebrain and neural
crest-derived cartilages of the face and jaw. Coloboma, a congenital eye
malformation, is associated with aberrant forebrain development
(holoprosencephaly) and with craniofacial defects (frontonasal dysplasia) in
humans, suggesting a critical role for cross-lineage interactions during retinal
morphogenesis. ZIC2, a zinc-finger transcription factor, is linked to human
holoprosencephaly. We have previously used morpholino assays to show zebrafish
zic2 functions in the developing forebrain, retina and craniofacial cartilage. We
now report that zebrafish with genetic lesions in zebrafish zic2 orthologs, zic2a
and zic2b, develop with retinal coloboma and craniofacial anomalies. We
demonstrate a requirement for zic2 in restricting pax2a expression and show
evidence that zic2 function limits Hh signaling. RNA-seq transcriptome analysis
identified an early requirement for zic2 in periocular neural crest as an
activator of alx1, a transcription factor with essential roles in craniofacial
and ocular morphogenesis in human and zebrafish. Collectively, these data
establish zic2 mutant zebrafish as a powerful new genetic model for in-depth
dissection of cell interactions and genetic controls during craniofacial complex
development.
PMID- 28689741
TI - Coconut oil has less satiating properties than medium chain triglyceride oil.
AB - It is well established that the consumption of medium-chain triglycerides (MCT)
can increase satiety and reduce food intake. Many media articles promote the use
of coconut oil for weight loss advocating similar health benefits to that of MCT.
The aim of this study was to examine the effect of MCT oil compared to coconut
oil and control oil on food intake and satiety. Following an overnight fast,
participants consumed a test breakfast smoothie containing 205kcal of either (i)
MCT oil (ii) coconut oil or (iii) vegetable oil (control) on three separate test
days. Participants recorded appetite ratings on visual analogue scales and were
presented with an ad libitum lunch meal of preselected sandwiches 180min after
consumption of the breakfast. The results showed a significant difference in
energy and macronutrient intakes at the ad libitum meal between the three oils
with the MCT oil reducing food intake compared to the coconut and control oil.
Differences in food intake throughout the day were found for energy and fat, with
the control having increased food intake compared to the MCT and coconut. The MCT
also increased fullness over the three hours after breakfast compared to the
control and coconut oils. The coconut oil was also reported as being less
palatable than the MCT oil. The results of this study confirm the differences
that exist between MCT and coconut oil such that coconut oil cannot be promoted
as having similar effects to MCT oil on food intake and satiety.
PMID- 28689740
TI - Clinical presentation and outcome in a series of 32 patients with 2
methylacetoacetyl-coenzyme A thiolase (MAT) deficiency.
AB - 2-methylacetoacetyl-coenzyme A thiolase (MAT) deficiency, also known as beta
ketothiolase deficiency, is an inborn error of ketone body utilization and
isoleucine catabolism. It is caused by mutations in the ACAT1 gene and may
present with metabolic ketoacidosis. In order to obtain a more comprehensive view
on this disease, we have collected clinical and biochemical data as well as
information on ACAT1 mutations of 32 patients from 12 metabolic centers in five
countries. Patients were between 23months and 27years old, more than half of them
were offspring of a consanguineous union. 63% of the study participants presented
with a metabolic decompensation while most others were identified via newborn
screening or family studies. In symptomatic patients, age at manifestation ranged
between 5months and 6.8years. Only 7% developed a major mental disability while
the vast majority was cognitively normal. More than one third of the identified
mutations in ACAT1 are intronic mutations which are expected to disturb splicing.
We identified several novel mutations but, in agreement with previous reports, no
clear genotype-phenotype correlation could be found. Our study underlines that
the prognosis in MAT deficiency is good and MAT deficient individuals may remain
asymptomatic, if diagnosed early and preventive measures are applied.
PMID- 28689742
TI - Overcoming neonatal sickness: Sex-specific effects of sickness on physiology and
social behavior.
AB - Early-life environmental stressors, including sickness, have the potential to
disrupt development in ways that could severely impact fitness. Despite what is
known about the effects of sickness on reproduction, the precise physiological
mechanisms have not yet been determined. The goal of this study was to
investigate the effects of a neonatal immune challenge on adult reproductive
physiology and opposite-sex social behavior. Male and female Siberian hamster
(Phodopus sungorus) pups were administered lipopolysaccharide ([LPS]; a cell wall
component of gram-negative bacteria) or saline injections on postnatal days 3 and
5 and body mass, food intake, and measures of reproductive maturity were taken
throughout development. In adulthood, hamsters were placed in staged mating pairs
with reproductively mature individuals of the opposite sex, during which a series
of behaviors were scored. We found that although males and females showed no
change in food intake, body mass, or reproductive behaviors, LPS-treated females
had abnormal estrous cycles and smaller ovaries. Females also showed increased
investigation of and increased aggression towards males in a reproductive
context. In contrast, LPS-treated males showed no change in any physiological
measures, nor did they show any changes in behavior. The present findings
demonstrate that females may be more robustly affected by neonatal sickness than
males and that these effects could have potential impacts on reproductive
success. Collectively, the results of this study can be used to expand upon what
is already known about sickness and reproduction, specifically the importance of
social behaviors involved in pre-copulation and information necessary to choose
the appropriate mate.
PMID- 28689743
TI - Insights into transgenerational epigenetics from studies of ciliates.
AB - Epigenetics, a term with many meanings, can be broadly defined as the study of
dynamic states of the genome. Ciliates, a clade of unicellular eukaryotes, can
teach us about the intersection of epigenetics and evolution due to the
advantages of working with cultivable ciliate lineages, plus their tendency to
express extreme phenotypes such as heritable doublet morphology. Moreover,
ciliates provide a powerful model for studying epigenetics given the presence of
dimorphic nuclei - a somatic macronucleus and germline micronucleus - within each
cell. Here, we exemplify the power of studying ciliates to learn about epigenetic
phenomena. We highlight "classical" examples from morphology and physiology
including cortical inheritance, mating type determination, and serotype
expression. In addition, we detail molecular studies of epigenetic phenomena,
including: DNA elimination; alternative processing and unscrambling; and copy
number determination. Based on the implications of these studies, we discuss
epigenetics as a possible functional mechanism for rapid speciation in ciliates.
PMID- 28689744
TI - The diagnostic advantage of EOB-MR imaging over CT in the detection of liver
metastasis in patients with potentially resectable pancreatic cancer:
Methodological issues.
PMID- 28689745
TI - Itching for change: Embracing modern flea and tick product development.
AB - The development and regulatory approval of ectoparasiticides, including flea and
tick control products, involves decades-old methods and the use of large numbers
of animals to evaluate toxicity and efficacy. Animals also are used to rear
(breed and feed) fleas and ticks for later use in testing. Non-animal methods for
regulatory-required testing and rearing currently exist and, with further
development, others could soon become available. Here we provide an overview of
the state-of-the-science of non-animal methods for rearing and regulatory
required efficacy testing of flea and tick control products. Several remaining
challenges as well as recommendations on the steps needed to replace animals in
the evaluation of these products are discussed.
PMID- 28689746
TI - Steps towards the international regulatory acceptance of non-animal methodology
in safety assessment.
AB - The current animal-based paradigm for safety assessment must change. In September
2016, the UK National Centre for Replacement, Refinement and Reduction of Animals
in Research (NC3Rs) brought together scientists from regulatory authorities,
academia and industry to review progress in bringing new methodology into
regulatory use, and to identify ways to expedite progress. Progress has been
slow. Science is advancing to make this possible but changes are necessary. The
new paradigm should allow new methodology to be adopted once it is developed
rather than being based on a fixed set of studies. Regulatory authorities can
help by developing Performance-Based Standards. The most pressing need is in
repeat dose toxicology, although setting standards will be more complex than in
areas such as sensitization. Performance standards should be aimed directly at
human safety, not at reproducing the results of animal studies. Regulatory
authorities can also aid progress towards the acceptance of non-animal based
methodology by promoting "safe-haven" trials where traditional and new
methodology data can be submitted in parallel to build up experience in the new
methods. Industry can play its part in the acceptance of new methodology, by
contributing to the setting of performance standards and by actively contributing
to "safe-haven" trials.
PMID- 28689747
TI - Hypoxia inhibits growth, proliferation, and increases response to chemotherapy in
retinoblastoma cells.
AB - Retinoblastoma is a malignant tumor of the retina and the most frequent
intraocular cancer in children. Low oxygen tension (hypoxia) is a common
phenomenon in advanced retinoblastomas, but its biological effect on
retinoblastoma growth is not clearly understood. Here we studied how hypoxia
altered retinoblastoma gene expression and modulated growth and response to
chemotherapy. The hypoxic marker lysyl oxidase (LOX) was expressed in 8 of 12
human retinoblastomas analyzed by immunohistochemistry, suggesting that a hypoxic
microenvironment is present in up to two thirds of the cases. WERI Rb1 and Y79
retinoblastoma lines were exposed to 1% or 5% pO2, cobalt chloride (CoCl2), or to
normoxia (21% pO2) for up to 8 days. Both 1% and 5% pO2 inhibited growth of both
lines by more than 50%. Proliferation was reduced by 25-50% when retinoblastoma
cells were exposed to 1% vs 21% pO2, as determined by Ki67 assay. Surprisingly,
Melphalan, Carboplatin, and Etoposide produced greater reduction in growth and
survival of hypoxic cells than normoxic ones. Gene expression profile analysis of
both lines, exposed for 48 h to 1%, 5%, or 21% pO2, showed that glycolysis and
glucose transport were the most up-regulated pathways, whereas oxidative
phosphorylation was the most down-regulated pathway in hypoxia as compared to
normoxia. These data support a role for hypoxia in suppressing growth,
proliferation, and enhancing response of retinoblastoma cells to chemotherapy,
possibly by impairing energy production through activation of glycolysis and
inhibition of mitochondrial respiration. Targeting glucose metabolism or
enhancing delivery of chemotherapeutic agents to hypoxic regions may improve
treatment of advanced retinoblastomas.
PMID- 28689748
TI - In-vivo corneal pulsation in relation to in-vivo intraocular pressure and corneal
biomechanics assessed in-vitro. An animal pilot study.
AB - The aim was to ascertain whether the characteristics of the corneal pulse (CP)
measured in-vivo in a rabbit eye change after short-term artificial increase of
intraocular pressure (IOP) and whether they correlate with corneal biomechanics
assessed in-vitro. Eight New Zealand white rabbits were included in this study
and were anesthetized. In-vivo experiments included simultaneous measurements of
the CP signal, registered with a non-contact method, IOP, intra-arterial blood
pressure, and blood pulse (BPL), at the baseline and short-term elevated IOP.
Afterwards, thickness of post-mortem corneas was determined and then uniaxial
tensile tests were conducted leading to estimates of their Young's modulus (E).
At the baseline IOP, backward stepwise regression analyses were performed in
which successively the ocular biomechanical, biometric and cardiovascular
predictors were separately taken into account. Results of the analysis revealed
that the 3rd CP harmonic can be statistically significantly predicted by E and
central corneal thickness (Models: R2 = 0.662, p < 0.005 and R2 = 0.832, p <
0.001 for the signal amplitude and power, respectively). The 1st CP harmonic can
be statistically significantly predicted by the amplitude and power of the 1st
BPL harmonic (Models: R2 = 0.534, p = 0.015 and R2 = 0.509, p < 0.018,
respectively). For elevated IOP, non-parametric analysis indicated significant
differences for the power of the 1st CP harmonic (Kruskal-Wallis test; p = 0.031)
and for the mean, systolic and diastolic blood pressures (p = 0.025, p = 0.019, p
= 0.033, respectively). In conclusion, for the first time, the association
between parameters of the CP signal in-vivo and corneal biomechanics in-vitro was
confirmed. In particular, spectral analysis revealed that higher amplitude and
power of the 3rd CP harmonic indicates higher corneal stiffness, while the 1st CP
harmonic correlates positively with the corresponding harmonic of the BPL signal.
PMID- 28689749
TI - Iontophoresis-assisted accelerated riboflavin/ultraviolet A scleral cross
linking: A potential treatment for pathologic myopia.
AB - Scleral collagen cross-linking is one of the most promising treatments to control
the pathologic process of myopia. However, the exact procedure and its impact on
animal models of myopia are still to be explored. We modified the scleral
riboflavin/ultraviolet A (UVA) cross-linking procedure with an iontophoresis
assisted drug delivery system and an accelerated UVA irradiation (10 mW/cm2, 9
min) and applied this treatment to an animal model of myopia. Ninety-six New
Zealand White rabbits developed relatively stable myopia by visual deprivation
and then underwent the modified scleral cross-linking surgery. All the statistics
and sample collection were obtained from 4 postoperative time points (1-day, 10
day, 1-month and 3-month groups). We found that the ultimate stress, Young's
modulus and physiological Young's modulus of treated myopia sclera were
significantly increased and maintained in 4 groups. The abnormal elongation of
the myopic eye was effectively controlled 1 month after the treatment and even
almost halted 3 months after the treatment. The histochemical assay revealed no
notable post-surgery damage or apoptosis in the retina and choroid. Vigorous
collagen synthesis was observed in scleral fibroblasts of the treated samples but
were rarely observed in the untreated ones under electron microscopy.
Furthermore, the remarkable difference in collagen gene expression and protein
content between treated and untreated samples also indicated that an alteration
in collagen metabolism may be triggered by the treatment. The effectiveness and
safety exploration suggested that the modified scleral cross-linking procedure
may be a potential method to control the pathologic process of myopia.
PMID- 28689750
TI - Characteristics and Long-Term Prognosis of Patients <=35 Years of Age with ST
Segment Elevation Myocardial Infarction and "Normal or Near Normal" Coronary
Arteries.
AB - There are scarce data regarding risk factors and prognosis of patients with
premature ST segment elevation myocardial infarction (STEMI) and "normal or near
normal" coronary arteries (N/NNCAs). We compared the characteristics and long
term prognosis of patients with premature STEMI and N/NNCAs with their
counterparts with significant coronary artery disease (CAD). We recruited 330
patients who had STEMI <=35 years of age and 167 age- and gender-matched
controls. All patients underwent coronary angiography. Coronary arteries with no
lesions or lesions causing <30% reduction in lumen diameter were defined as
N/NNCAs, whereas narrowings causing >=50% diameter reduction formed the
significant CAD group. Lipid profile, homocysteine levels, and
methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism were determined.
Sixty patients (18%) had N/NNCAs. Patients with N/NNCAs had lower low-density
lipoprotein-cholesterol and higher high-density lipoprotein-cholesterol levels,
higher homocysteine levels, and higher prevalence of MTHFR TT genotype (34.6 vs
18%, p = 0.008) compared with patients with significant CAD. After a median
follow-up of 8 years, cardiovascular events occurred in 105 (36%) of 291 patients
with available follow-up data. Significant CAD was associated with higher risk
for recurrent cardiovascular events after adjustment for traditional risk factors
(hazard ratio 2.095, 95% confidence interval 1.088 to 3.664, p = 0.022) and
additional adjustment for the left ventricular ejection fraction, reperfusion
therapy, and persistent smoking (hazard ratio 1.869, 95% confidence interval
1.007 to 3.468, p = 0.041). In conclusion, patients with premature STEMI and
N/NNCAs have fewer lipid abnormalities, higher homocysteine levels and prevalence
of MTHFR TT genotype, and better long-term prognosis compared with their
counterparts with significant CAD.
PMID- 28689751
TI - Postprocedural Changes of Tricuspid Regurgitation After MitraClip Therapy for
Mitral Regurgitation.
AB - The effect of percutaneous mitral valve repair using the MitraClip system on
tricuspid regurgitation (TR) has not been well investigated. We retrospectively
analyzed 102 consecutive patients who underwent the successful MitraClip
procedure, and who also had a preprocedural and 1-year follow-up transthoracic
echocardiography. TR severity was graded by standard guideline-recommended
criteria. At 1 year after the MitraClip procedure, the degree of TR regressed (at
least 1 grade) in 23% of the patients, was unchanged in 62% of the patients, and
progressed in 16% of the patients. Compared with patients in the other groups,
the patients with TR regression had a greater severity of TR at baseline. The TR
regression group showed a significant reduction in the systolic pulmonary artery
pressure (sPAP) (49 +/- 13 to 37 +/- 11 mm Hg, p <0.05), a right-sided cardiac
reverse remodeling (right ventricular diameter: 41 +/- 7 to 39 +/- 7 mm,
tricuspid annular diameter: 48 +/- 8 to 46 +/- 9 mm, both p <0.05), and an
increase in the right ventricular fractional area change (38 +/- 7 to 40 +/- 7%,
p <0.05). In the multivariate analysis, the decrease in sPAP was the only
independent parameter change associated with TR regression. In conclusion, TR
regression was observed in 23% of the patients after the successful MitraClip
procedures, and favorable echocardiographic parameter changes were detected in
this group. Only a reduction in sPAP was independently associated with TR
regression.
PMID- 28689752
TI - Effect of Hospital Ownership on Outcomes of Heart Failure Hospitalization.
AB - This study aimed to evaluate the impact of hospital ownership on heart failure
(HF) hospitalization outcomes in the United States using data from the National
Inpatient Sample of the Agency for Healthcare Research and Quality. Hospital
ownership was classified into three, namely, nonfederal government, not-for
profit, and for-profit hospitals. Participants were adults hospitalized with a
primary diagnosis of HF (2013 to 2014). End points included inpatient mortality,
length-of-stay, cost and charge of hospitalization, and disposition at discharge.
Of the estimated 1.9 million HF hospitalizations in the United States between
2013 and 2014, 73% were in not-for-profit hospitals, 15% were in for-profit
hospitals, and 12% were in nonfederal government hospitals. Overall, mortality
rate was 3%, mean length of stay was 5.3 days, median cost of hospitalization was
USD 7,248, and median charge was USD 25,229, and among those who survived to
hospital discharge, 51% had routine home discharge. There was no significant
difference in inpatient mortality between hospital ownership among male patients,
but there was a significant difference for female patients. Compared with
government hospitals, mortality in female patients was lower in not-for-profit
(odds ratio: 0.85 [95% confidence interval: 0.77 to 0.94]) and for-profit
hospitals (odds ratio: 0.77 [0.68 to 0.87]). In addition, mean length of stay was
highest in not-for-profit hospitals (5.4 days) and lowest in for-profit hospitals
(5 days). Although cost of hospitalization was highest in not-for-profit
hospitals (USD 7462) and lowest in for-profit hospitals (USD 6,290), total charge
billed was highest in for-profit hospitals (USD 35,576) and lowest in government
hospitals (USD 19,652). The average charge-to-cost ratio was 3:1 for government
hospitals, 3.5:1 for not-for-profit hospitals, and 5.9:1 for for-profit
hospitals. In conclusion, there exist significant disparities in HF
hospitalization outcomes between hospital ownerships. Outcomes were generally
better in for-profit hospitals than other tiers of hospital and, notably, there
was a significant difference in inpatient mortality for female patients (but not
for male patients).
PMID- 28689753
TI - Comparison of Left Ventricular Function and Myocardial Infarct Size Determined by
2-Dimensional Speckle Tracking Echocardiography in Patients With and Without
Chronic Obstructive Pulmonary Disease After ST-Segment Elevation Myocardial
Infarction.
AB - Patients with chronic obstructive pulmonary disease (COPD) have a high risk of
mortality after acute ST-segment elevation myocardial infarction (STEMI). We
compared STEMI patients with versus without COPD in terms of infarct size and
left ventricular (LV) systolic function using advanced 2-dimensional speckle
tracking echocardiography. Of 1,750 patients with STEMI (mean age 61 +/- 12
years, 76% male), 133 (7.6%) had COPD. With transthoracic echocardiography, left
ventricular ejection fraction (LVEF) and wall motion score index were measured.
Infarct size was assessed using biomarkers (creatine kinase and troponin T). LV
global longitudinal strain (GLS), reflecting active LV myocardial deformation,
was measured with 2-dimensional speckle tracking echocardiography to estimate LV
systolic function and infarct size. STEMI patients with COPD were significantly
older, more likely to be former smokers, and had worse renal function compared
with patients without COPD. There were no differences in infarct size based on
peak levels of creatine kinase (1315 [613 to 2181] vs 1477 [682 to 3047] U/l, p =
0.106) and troponin T (3.3 [1.4 to 7.3] vs 3.9 [1.5 to 7.8] ug/l, p = 0.489).
Left ventricular ejection fraction (46% vs 47%, p = 0.591) and wall motion score
index (1.38 [1.25 to 1.66] vs 1.38 [1.19 to 1.69], p = 0.690) were comparable. In
contrast, LV GLS was significantly more impaired in patients with COPD compared
with patients without COPD (-13.9 +/- 3.0% vs -14.7 +/- 3.9%, p = 0.034). In
conclusion, despite comparable myocardial infarct size and LV systolic function
as assessed with biomarkers and conventional echocardiography, patients with COPD
exhibit more impaired LV GLS on advanced echocardiography than patients without
COPD, suggesting a greater functional impairment at an early stage after STEMI.
PMID- 28689754
TI - Sociodemographic and clinical correlates of psychotic symptoms in the general
population: Findings from the MHGP survey.
AB - BACKGROUND: We aimed to explore the sociodemographic and psychiatric correlates
of psychotic symptoms in a large general population sample. METHODS: The French
Mental Health in the General Population cross-sectional survey interviewed 38,694
individuals using the Mini International Neuropsychiatric Interview. We looked
for associations between the presence of lifetime psychotic symptoms,
sociodemographic characteristics (including migrant status over three
generations) and clinical characteristics. We then looked for associations
regarding only hallucinations, delusional symptoms, and the co-occurrence of both
hallucinations and delusional symptoms. To test the psychosis continuum
hypothesis, associations with sociodemographic characteristics were compared with
the characterized psychotic disorders' associations. RESULTS: We found that 22.3%
of the population declared psychotic symptoms without psychotic disorders,
including 5.7% who declared hallucinations, 20.5% delusional symptoms, 4.0% both
hallucinations and delusional symptoms, and 2.8% characterized psychotic
disorders. The presence of psychotic symptoms was associated with young age,
migrant status (over three generations), secondary education level, low-income
level and never-married and separated marital status. Hallucinations, delusional
symptoms and the co-occurrence of both hallucinations and delusional symptoms
showed the same correlates, and hallucinations were also associated with
elementary education level. Characterized psychotic disorders showed the same
correlates. Concerning clinical outcomes, the presence of psychotic symptoms,
hallucinations and delusional symptoms was associated with all non-psychotic
disorders, i.e., bipolar, depressive, alcohol use, generalized anxiety, social
phobia, panic and post-traumatic stress disorders and dysthymia (except
dysthymia, which was not associated with hallucinations). CONCLUSIONS: Our
results indicate that psychotic symptoms are associated with broad
psychopathologies and support the continuum model of psychosis.
PMID- 28689755
TI - Accelerated aging in schizophrenia and related disorders: Future research.
AB - Several lines of evidence suggest schizophrenia is a segmental progeria, that is,
some but not all aspects of accelerated aging may be present. However, the
evidence has not been consistent. Problems with matching and confounding may
account for some of these discrepancies. Given the etiopathophysiological
heterogeneity of schizophrenia, it is possible that only a specific
pathophysiological group within schizophrenia is associated with progeroid
features, while others are not, or that one group is associated with a particular
segment of aging features, while other progeroid features are found in another
pathophysiological subgroup. In the aging research field, significant progress
has been made in identifying the molecular pathways that confer aging: epigenetic
changes, inflammation, proteostasis, adult stem cell function, metabolic changes,
and adaptation to stress, and macromolecular damage. In addition to replication
and clarification of existing kinds of evidence, examining these aging pathways
would improve our understanding of progeria in schizophrenia.
PMID- 28689756
TI - Sensorimotor gating characteristics of violent men with comorbid psychosis and
dissocial personality disorder: Relationship with antisocial traits and
psychosocial deprivation.
AB - Evidence suggests violence amongst those with psychosis is not aetiologically
homogeneous, and that a large proportion of those who engage in violent behaviour
have a comorbid antisocial personality disorder. Initial investigations indicate
that this subgroup has distinct historical and neuropsychological
characteristics, which may indicate diverse treatment needs. This study
investigated sensorimotor gating characteristics of violent men with diagnoses of
both psychosis and dissocial personality disorder (DPD) (n=21) relative to
violent men with psychosis alone (n=12), DPD alone (n=14) and healthy, non
violent male controls (n=27), using the prepulse inhibition (PPI) paradigm. The
results indicated that, relative to the psychosis alone and healthy control
groups, the comorbid group had lower PPI, especially at 60-ms prepulse-to-pulse
interval. The DPD group took an intermediary position and did not differ from any
group. Antisocial personality traits (factor two scores of the Psychopathy
Checklist - Revised), and greater severity of childhood psychosocial deprivation
(including physical and sexual abuse), were significantly correlated with poor
PPI across the clinical sample. The findings suggest diverse sensorimotor gating
profiles amongst subgroups of violent offenders, with comorbid psychosis and DPD
showing most impairment. This is consistent with a 'double dose' of deficit
explanation amongst those with both diagnoses, explained at least in part by
presence of antisocial personality traits and childhood psychosocial deprivation.
PMID- 28689757
TI - Abnormal brain connectivity during error-monitoring in the psychosis high-risk
state.
PMID- 28689758
TI - White matter microstructure predicts cognitive training-induced improvements in
attention and executive functioning in schizophrenia.
AB - We examined the relationship between white matter microstructure in schizophrenia
using diffusion tensor imaging (DTI) and cognitive improvements induced by 70h
(~16weeks) of cognitive training. We measured anatomical connectivity in 48
patients with schizophrenia (SZ) and 28 healthy control participants (HC) at
baseline, and then examined the relationship between anatomical connectivity at
baseline and training-induced cognitive gains in 30 SZ who performed diffusion
imaging after completing 70h of training. Compared with healthy control
participants, individuals with schizophrenia showed reduced white matter
integrity at baseline, as indexed by fractional anisotropy metrics, in bilateral
posterior corona radiata, bilateral retrolenticular internal capsules, bilateral
posterior thalamic radiation, left anterior corona radiata, left superior
longitudinal fasciculus, left sagittal stratum, right cerebral peduncle and the
genu and splenium of the corpus callosum. After training, schizophrenia
participants showed significant gains in attention/vigilance, speed of
processing, verbal learning, visual learning and executive functioning. White
matter integrity within the right fronto-occipital fasciculus predicted training
induced improvements in attention/vigilance, while white matter integrity within
the right corticospinal tract and bilateral medial lemnisci predicted cognitive
training-induced improvements in executive functioning, areas that did not show
white matter tract deficits at baseline. These findings suggest that preserved
white matter integrity connecting long-range prefrontal-thalamic-sensorimotor
areas may be an important determinant for training-induced neurocognitive
plasticity.
PMID- 28689760
TI - A man with fever and rash.
PMID- 28689761
TI - A Combination of Thenar and Hypothenar Hammer Syndrome.
PMID- 28689759
TI - Amplification of F-Actin Disassembly and Cellular Repulsion by Growth Factor
Signaling.
AB - Extracellular cues that regulate cellular shape, motility, and navigation are
generally classified as growth promoting (i.e., growth factors/chemoattractants
and attractive guidance cues) or growth preventing (i.e., repellents and
inhibitors). Yet, these designations are often based on complex assays and
undefined signaling pathways and thus may misrepresent direct roles of specific
cues. Here, we find that a recognized growth-promoting signaling pathway
amplifies the F-actin disassembly and repulsive effects of a growth-preventing
pathway. Focusing on Semaphorin/Plexin repulsion, we identified an interaction
between the F-actin-disassembly enzyme Mical and the Abl tyrosine kinase.
Biochemical assays revealed Abl phosphorylates Mical to directly amplify Mical
Redox-mediated F-actin disassembly. Genetic assays revealed that Abl allows
growth factors and Semaphorin/Plexin repellents to combinatorially increase Mical
mediated F-actin disassembly, cellular remodeling, and repulsive axon guidance.
Similar roles for Mical in growth factor/Abl-related cancer cell behaviors
further revealed contexts in which characterized positive effectors of
growth/guidance stimulate such negative cellular effects as F-actin
disassembly/repulsion.
PMID- 28689762
TI - A toxicological review of the ethylene glycol series: Commonalities and
differences in toxicity and modes of action.
AB - This review summarizes the hazards, exposure and risk that are associated with
ethylene glycols (EGs) in their intended applications. Ethylene glycol (EG; CAS
RN 107-21-1) and its related oligomers include mono-, di-, tri-, tetra-, and
penta-EG. All of the EGs are quickly and extensively absorbed following ingestion
and inhalation, but not by the dermal route. Metabolism involves oxidation to the
mono- and dicarboxylic acids. Elimination is primarily through the urine as the
parent compound or the monoacid, and, in the case of EG, also as exhaled carbon
dioxide. All EGs exert acute toxicity in a similar manner, characterized by CNS
depression and metabolic acidosis in humans and rodents; the larger molecules
being proportionally less acutely toxic on a strict mg/kg basis. Species
differences exist in the metabolism and distribution of toxic metabolites,
particularly with the formation of glycolic acids and oxalates (OX) from EG and
diethylene glycol (DEG); OX are not formed to a significant degree in higher
ethylene glycols. Among rodents, rats are more sensitive than mice, and males
more sensitive than females to the acute and repeated-dose toxicity of EG. The
metabolic formation of glycolic acid (GA), diglycolic acid (DGA), and OX are
associated with nephrotoxicity in humans and rodents following single and
repeated exposures. However, physiological and metabolic differences in the rate
of formation of GA, DGA and OX and their distribution result in EG and DEG
causing embryotoxicity in rats, but not rabbits. This rodent-specific sensitivity
indicates that EG and its higher oligomers are not anticipated to be embryotoxic
in humans at environmentally relevant doses. None of the compounds present
developmental toxicity concerns at doses that do not also cause significant
maternal toxicity, nor do any of the EGs cause adverse effects on fertility. The
EGs are neither genotoxic nor carcinogenic. A read-across matrix is presented,
which considers the common and distinct toxicological properties of each
compound. It is concluded that EGs pose no risk to human health as a result of
their intended use patterns.
PMID- 28689763
TI - Remodeling of brain lipidome in methamphetamine-sensitized mice.
AB - Lipids are predominant components of the brain and key regulators for neural
structure and function. The effect of methamphetamine (METH) on behavior,
cognition as well as memory has been intensively investigated; however, the
impact of METH on brain lipid profiles is largely unknown. Here, we used a global
lipidomic approach to investigate brain lipidome of METH-sensitized mice. We
found that repeated METH significantly modified the lipidome in the hippocampus,
prefrontal cortex (PFC) and striatum. Interestingly, nucleus accumbens showed no
obvious alteration in lipidomic profiling. Phospholipid and sphingolipid
metabolisms were profoundly modified in the hippocampus of METH-sensitized mice,
exhibiting increased phosphatidic acid and ether phosphatidylcholine but
decreased lysophosphatidylethanolamine, lactosylceramide and triglycerides. The
fatty acyl length of phospholipids and diacylglycerol longer than 40 carbon were
clearly decreased in the hippocampus, and that 36 carbon was decreased in the
PFC. These results indicate METH can profoundly affect the metabolism of
phospholipids, sphingolipids and glycerolipids in the brain. Our findings reveal
a link between remodeled brain lipidome and neurobehavior induced by METH.
PMID- 28689764
TI - Wula (Voices) of Aboriginal women on barriers to accepting smoking cessation
support during pregnancy: Findings from a qualitative study.
AB - AIM: To gather Aboriginal women's stories of smoking and becoming pregnant to
identify the barriers in accepting smoking cessation support during pregnancy.
METHODS: Qualitative data were collected through use of yarning methodology
between August 2015 and January 2016 by an Aboriginal Researcher with experience
in social and community services. A short on-line survey was used to collect
quantitative data. Interviews only recorded the therapeutic yarning process,
which ranged from 9 to 45min duration, averaging 30min. Audio-recorded interviews
were transcribed and independently coded. A general inductive analysis was used
to determine emergent themes. RESULTS: Twenty Aboriginal women between 17-38
years of age, who were pregnant or recently given birth, living in the Hunter New
England (HNE) area took part. Eleven women were still smoking; nine had quit.
Most were highly aware of the implications of smoking for their babies. Major
themes identified for accepting support were: ambivalence towards a need for
support, health professional advice, reduction in smoking, and attitudes to
Nicotine Replacement Therapy (NRT). Women reported being advised to cut down,
rather than to quit; reducing consumption may be a barrier to accepting NRT.
Women recommended enhanced clinical support and Aboriginal community engagement
in cessation care. DISCUSSION/CONCLUSIONS: Aboriginal women in the HNE area
reported quitting or reducing their cigarette intake during pregnancy. Health
Professionals working with Aboriginal women during pregnancy should give
consistent messages to quit smoking completely, and offer increased, ongoing and
extensive smoking cessation support to Aboriginal mothers. Clinical practices
could partner with Aboriginal communities to support the delivery of smoking
cessation services.
PMID- 28689765
TI - Unanswered Questions in Contemporary Heart Failure.
AB - OBJECTIVE: The epidemiology of heart failure (HF) is changing. This study aimed
to describe questions that arise during the routine care of HF patients that are
unanswered by the current literature and describe how the type and focus of these
questions has changed over time. METHODS: Investigators from the National Heart,
Lung, and Blood Institute-sponsored Heart Failure Apprentice Network collected
and categorized questions from 5 academic hospitals over 12 months. A total of
174 unanswered questions were collected and analyzed. RESULTS: Compared with
2004, there were more unanswered questions about "whether" to use therapies and
fewer about "how" to use therapies. There were fewer questions about what
therapeutic targets, therapy adjustment, and combination therapies. There were
more questions about whether or how to stop therapies and how to add therapies
back. Newly prominent topics, not observed in 2004, including novel therapeutics,
refractory ventricular tachycardia, right heart failure, and nutrition/frailty,
accounted for 24% of questions. CONCLUSIONS: Compared with 2004, there are fewer
unanswered questions about how to use, adjust, and combine therapies. There were
more unanswered questions about whether and how to stop therapies. Almost 25% of
unanswered questions dealt with topics indicative of more advanced disease which
were not observed in 2004.
PMID- 28689766
TI - Acute administration of tramadol and tapentadol at effective analgesic and
maximum tolerated doses causes hepato- and nephrotoxic effects in Wistar rats.
AB - Tramadol and tapentadol are two atypical synthetic opioid analgesics, with
monoamine reuptake inhibition properties. Mainly aimed at the treatment of
moderate to severe pain, these drugs are extensively prescribed for multiple
clinical applications. Along with the increase in their use, there has been an
increment in their abuse, and consequently in the reported number of adverse
reactions and intoxications. However, little is known about their mechanisms of
toxicity. In this study, we have analyzed the in vivo toxicological effects in
liver and kidney resulting from an acute exposure of a rodent animal model to
both opioids. Male Wistar rats were intraperitoneally administered with 10, 25
and 50mg/kg tramadol and tapentadol, corresponding to a low, effective analgesic
dose, an intermediate dose and the maximum recommended daily dose, respectively,
for 24h. Toxicological effects were assessed in terms of oxidative stress,
biochemical and metabolic parameters and histopathology, using serum and urine
samples, liver and kidney homogenates and tissue specimens. The acute exposure to
tapentadol caused a dose-dependent increase in protein oxidation in liver and
kidney. Additionally, exposure to both opioids led to hepatic commitment, as
shown by increased serum lipid levels, decreased urea concentration, increased
alanine aminotransferase and decreased butyrylcholinesterase activities. It also
led to renal impairment, as reflected by proteinuria and decreased glomerular
filtration rate. Histopathological findings included sinusoidal dilatation,
microsteatosis, vacuolization, cell infiltrates and cell degeneration, indicating
metabolic changes, inflammation and cell damage. In conclusion, a single
effective analgesic dose or the maximum recommended daily dose of both opioids
leads to hepatotoxicity and nephrotoxicity, with tapentadol inducing
comparatively more toxicity. Whether these effects reflect risks during the
therapeutic use or human overdoses requires focused attention by the medical
community.
PMID- 28689767
TI - Commentary on: Brody et al., 2017 "Diversity dynamics: Issues and strategies to
create positive organizations: The experience of male Robert Wood Johnson
Foundation Nurse Faculty Scholars".
PMID- 28689768
TI - Use of bone turnover markers in postmenopausal osteoporosis.
AB - Bone turnover comprises two processes: the removal of old bone (resorption) and
the laying down of new bone (formation). N-terminal propeptide of type I
procollagen (PINP) and C-telopeptide of type I collagen (CTX-I) are markers of
bone formation and resorption, respectively, that are recommended for clinical
use. Bone turnover markers can be measured on several occasions in one individual
with good precision. However, these markers are subject to several sources of
variability, including feeding (resorption decreases) and recent fracture (all
markers increase for several months). Bone turnover markers are not used for
diagnosis of osteoporosis and do not improve prediction of bone loss or fracture
within an individual. In untreated women, very high bone turnover marker
concentrations suggest secondary causes of high bone turnover (eg, bone
metastases or multiple myeloma). In people with osteoporosis, bone turnover
markers might be useful to assess the response to anabolic and antiresorptive
therapies, to assess compliance to therapy, or to indicate possible secondary
osteoporosis. Much remains to be learnt about how bone turnover markers can be
used to monitor the effect of stopping bisphosphonate therapy (eg, to identify a
threshold above which restarting therapy should be considered). More studies are
needed to investigate the use of bone turnover markers for assessment of the bone
safety of new medications.
PMID- 28689770
TI - VIP induces the decidualization program and conditions the immunoregulation of
the implantation process.
AB - The decidualization process involves phenotype and functional changes on
endometrial cells and the modulation of mediators with immunoregulatory
properties as the vasoactive intestinal peptide (VIP). We investigate VIP
contribution to the decidualization program and to immunoregulation throughout
the human embryo implantation process. The decidualization of Human endometrial
stromal cell line (HESC) with Medroxyprogesterone-dibutyryl-cAMP increased
VIP/VPAC-receptors system. In fact, VIP could induce decidualization increasing
differentiation markers (IGFBP1, PRL, KLF13/KLF9 ratio, CXCL12, CXCL8 and CCL2)
and allowing Blastocyst-like spheroids (BLS) invasion in an in vitro model of
embryo implantation. Focus on the tolerogenic effects, decidualized cells induced
a semi-mature profile on maternal dendritic cells; restrained CD4+ cells
recruitment while increased regulatory T-cells recruitment. Interestingly, the
human blastocyst conditioned media from developmentally impaired embryos
diminished the invasion and T-regulatory cells recruitment in these settings.
These evidences suggest that VIP contributes to the implantation process inducing
decidualization, allowing BLS invasion and favoring a tolerogenic micro
environment.
PMID- 28689769
TI - Osteoporosis treatment: recent developments and ongoing challenges.
AB - Osteoporosis is an enormous and growing public health problem. Once considered an
inevitable consequence of ageing, it is now eminently preventable and treatable.
Ironically, despite tremendous therapeutic advances, there is an increasing
treatment gap for patients at high fracture risk. In this Series paper, we trace
the evolution of drug therapy for osteoporosis, which began in the 1940s with the
demonstration by Fuller Albright that treatment with oestrogen could reverse the
negative calcium balance that developed in women after menopause or oophorectomy.
We note a watershed in osteoporosis drug discovery around the year 2000, when the
approach to developing novel therapeutics shifted from one driven by discoveries
in animal studies and clinical observations (eg, oestrogen, calcitonin, and
teriparatide) or opportunistic repurposing of existing compounds (eg,
bisphosphonates) to one driven by advances in fundamental bone biology (eg,
denosumab) coupled with clues from patients with rare bone diseases (eg,
romosozumab, odanacatib). Despite these remarkable advances, concerns about rare
side-effects of anti-resorptive drugs, particularly bisphosphonates, and the
absence of clear evidence in support of their long-term efficacy is leading many
patients who could benefit from drug therapy to not take these drugs. As such,
there remains an important clinical need to develop ways to enhance patient
acceptance and compliance with these effective drugs, and to continue to develop
new drugs that do not cause these side-effects and have prolonged anabolic
effects on bone. Such changes could lead to a true reversal of this potentially
devastating disease of ageing.
PMID- 28689771
TI - Immunosuppression with tacrolimus improved implantation and rescued expression of
uterine progesterone receptor and its co-regulators FKBP52 and PIASy at nidation
in the obese and diabetic mice: Comparative studies with metformin.
AB - Diabesity is often associated with subfertility and recurrent miscarriages.
Evidence links systemic and local uterine cytotoxicity to the pathogenesis of
implantation failure (IF) in diabetes. Immunosuppression with tacrolimus improved
pregnancy outcomes in obese and diabetic mice and repeated IF in women with
elevated Th1/Th2 blood cell ratios. However the mode of action of tacrolimus in
protecting against IF and the molecular mechanisms associated with recurrent
miscarriages in the obese and diabetic subjects are yet to be elucidated. Here we
administered tacrolimus (FK506) (0.1 mg/kg) for four consecutive weeks to the
NONcNZO10/LtJ mice, a model of human PCOS, chronically fed with 60% kCal fat for
16 consecutive weeks to simulate human obesity-associated T2DM. Compared to those
immunosuppressed with tacrolimus and their normative controls, high-fat fed (HFD)
diabetic NONcNZO mice exhibited higher rates of peri- and post-implantation
resorption and had aberrant expression of uterine IFNgamma and progesterone
receptor (PGR) and its immunophilin co-chaperone FKBP52 at nidation. Immature
uterodomes and lack of activation of uterine STAT3 and NFkappaB at implantation
were characteristics of IF in the HFD-dNONcNZO dams also low in the deciduogenic
factors IL11 and GM-CSF. Therapeutic interventions with tacrolimus or metformin
normalized the expression of decidual IFNgamma, PGR and FKBP52, increased co
localization of protein inhibitor of activated STATy (PIASy) to PGR and resulted
in the upregulation of uterine IL11and LIF. Rescued phosphorylation of STAT3 and
NFkappaBp65 and uterodome maturation at nidation defined implantation success in
treated dams. To our knowledge this is the first report to show that the impact
of HFD on the hemochorial implantation is at least in part mediated through
disruption of PGR signaling at nidation and that immunosuppression with
tacrolimus or treatment with metformin restores PGR-mediated influences during
implantation in the obese and diabetic subjects.
PMID- 28689772
TI - Characterization and function of a beta-catenin homolog from Litopenaeus vannamei
in WSSV infection.
AB - As a conserved signaling pathway, Wnt/beta-catenin signaling pathway participates
in many physiological activities, including cell differentiation, apoptosis and
so on. beta-catenin is the key molecule of Wnt/beta-catenin signaling pathway and
plays a pivotal role. In this article, a beta-catenin homolog from Litopenaeus
vannamei (designed as Lv-beta-catenin) was cloned and its role in WSSV infection
was investigated. Sequence analysis suggested that Lv-beta-catenin had characters
of beta-catenin family. Semi-quantitative RT-PCR showed that Lv-beta-catenin
transcripted in all detected tissues. In the subsequent WSSV infection
experiments, it was found that the transcription levels of Lv-beta-catenin were
down-regulated, as well as the expression levels. Immunofluorescence assay
further confirmed that WSSV could reduce the amount of Lv-beta-catenin and
promoted Lv-beta-catenin to translocate into the nucleus. Moreover, we found that
WSSV could influence the amount of Lv-beta-catenin by ubiquitination. While Lv
beta-catenin was up-regulated by a beta-catenin activator GSK-3 Inhibitor IX, the
transcription of virus immediate early gene WSSV069 was significantly inhibited.
In addition, it was found that Lv-beta-catenin could interact with WSSV069.
Conclusively, our study provided evidences that beta-catenin may participate in
the WSSV infection, and Wnt/beta-catenin signal pathway may play an important
role in immune regulation.
PMID- 28689773
TI - The toll-like receptor ligands Hiltonol(r) (polyICLC) and imiquimod effectively
activate antigen-specific immune responses in Tasmanian devils (Sarcophilus
harrisii).
AB - Devil facial tumour disease (DFTD) describes two genetically distinct
transmissible tumours that pose a significant threat to the survival of the
Tasmanian devil. A prophylactic vaccine could protect devils from DFTD
transmission. For this vaccine to be effective, potent immune adjuvants will be
required. Toll-like receptors (TLRs) promote robust immune responses in human
cancer studies and are highly conserved across mammalian species. In this study,
we investigated the proficiency of TLR ligands for immune activation in the
Tasmanian devil using in vitro mononuclear cell stimulations and in vivo
immunisation trials with a model antigen. We identified two such TLR ligands,
polyICLC (Hiltonol(r)) (TLR3) and imiquimod (TLR7), that in combination induced
significant IFNgamma production from Tasmanian devil lymphocytes in vitro.
Immunisation with these ligands and the model antigen keyhole limpet haemocyanin
activated robust antigen-specific primary, secondary and long-term memory IgG
responses. Our results support the conserved nature of TLR signaling across
mammalian species. PolyICLC and imiquimod will be trialed as immune adjuvants in
future DFTD vaccine formulations.
PMID- 28689774
TI - Expression of IL-1Ra, IL-6, IL-8, IL-18, TNF-alpha and IFN-gamma genes in
peripheral blood leukocytes of rabbits infected with RHDV (Rabbit Haemorrhagic
Disease Virus).
AB - Rabbit haemorrhagic disease virus (RHDV) induces a highly contagious and
extremely lethal disease that fulfils many requirements of an animal model of
fulminant hepatic failure (FHF); however, the pathogenesis of RHD has still not
been fully elucidated. Cytokines play an important role in regulation of the
immune response and pathogenesis of many diseases, including those caused by
viral infections. Furthermore, recent studies indicate a role of the immune
response, especially peripheral blood leukocytes (PBL), in the pathogenesis of
RHD. Thus, in the present study we investigated the expression of IL-1Ra, IL-6,
IL-8, IL-18, TNF-alpha and IFN-gamma genes in PBL of RHDV-infected rabbits. We
also compared the expression of genes encoding these cytokines in rabbits with
different course of RHDV infection (in animals that died 36 h post infection or
survived even over 60 h after infection). The study revealed increased expression
of genes encoding pro-inflammatory cytokines: IL-6, IL-8, TNF-alpha, IFN-gamma in
PBL of RHDV-infected rabbits. Moreover, the level of cytokine gene expression
depended on the course of RHD. Hence, the results obtained indicate the potential
role of these cytokines in RHDV infection and their influence on the survival
time of infected rabbits.
PMID- 28689775
TI - Gene characteristics, immune and stress responses of PmPrx1 in black tiger shrimp
(Penaeus monodon): Insights from exposure to pathogenic bacteria and toxic
environmental stressors.
AB - Peroxiredoxins (Prxs) are ubiquitous, multifunctional and evolutionarily
conserved enzymes that can protect cells from oxidative damage caused by ROS and
play a vital role in immune responses. Here, a full-length Prx1 cDNA sequence
(PmPrx1) was isolated from Penaeus monodon. The PmPrx1 cDNA was 951 base pairs
(bp), encoding 198 amino acid polypeptides. The results of qRT-PCR showed that
the PmPrx1 mRNA was ubiquitously expressed in all tissues tested and had a
comparatively high expression level in immune-associated tissues (gill,
hepatopancreas). To explore the immune and anti-stress roles of PmPrx1, the gills
and hepatopancreas were chosen as target tissues in Penaeus monodon and were
challenged with bacteria (Vibrio harveyi and Streptococcus agalactiae) and toxic
environmental stresses. To further clarify the immune function of PmPrx1 after
bacterial challenge, the recombinant PmPrx1 protein was acquired using a
prokaryotic expression method. The antioxidant activity of the recombinant PmPrx1
was assessed by the catalyzing hydrogen peroxide assay method, and the results
showed obvious antioxidant activity in a dose-dependent and temperature-dependent
manner. The antimicrobial activity of purified PmPrx1 protein was evaluated and
further studied in vitro relying on a bacterial growth inhibition test which was
conducted in both liquid and solid cultures. Furthermore, E. coli transferred
with pRSET-PmPrx1 was dramatically protected in response to metal toxicity and
H2O2 oxidative stress. In summary, this study provides useful information about
the role of the Prx1 gene in defense against a variety of toxic factors in
shrimps that help to further clarify the functional mechanism of Prx.
PMID- 28689776
TI - Diagnostic Challenges in the Era of Canine Leishmania infantum Vaccines.
AB - The diagnosis of canine leishmaniosis (CanL) is complex due to its variable
clinical manifestations and laboratory findings. The availability of vaccines to
prevent CanL has increased the complexity of diagnosis, as serological tests may
not distinguish between naturally infected and vaccinated dogs. Current practices
of prevaccination screening are not sufficiently sensitive to detect
subclinically infected dogs, resulting in the vaccination of infected animals,
which may lead to disease in vaccinated dogs that are also infectious to sand
flies. This review evaluates the current techniques for diagnosing CanL, and
focuses on new challenges raised by the increasing use of vaccines against this
disease. Important gaps in knowledge regarding the diagnosis of CanL are
underscored to highlight the need for novel diagnostic test development.
PMID- 28689777
TI - Corrigendum to "Evolvosides C-E, flavonol-4'-O-triglycosides from Evolvulus
alsinoides and their anti-stress activity" [Bioorg. Med. Chem. 21 (2013) 1116
1122].
PMID- 28689778
TI - Urinary Diversion With vs Without Bowel Anastomosis in Patients With an Existing
Colostomy: A Multi-institutional Study.
AB - OBJECTIVE: To describe the short-term outcomes with the bowel anastomosis (BA)
approach vs the no-bowel anastomosis (NBA) approach in adult patients undergoing
urinary diversion. METHODS: A chart review was performed of adults undergoing
urinary diversion from 2006 to 2015. Patients with a pre-existing colostomy were
divided into NBA and BA groups. Postoperative complications were recorded per the
Clavien-Dindo system. Variables were compared using the BA group as a control. A
2-tailed t test was used to compare means. RESULTS: A total of 43 patients were
included: 33 in the BA group and 10 in the NBA. No significant differences were
found between the 2 groups for the comorbidity index (P = .16), the body mass
index (P = .54), or radiation history (P = .90). In the NBA and BA groups, the
median blood loss was 250 and 300 mL (P = .11); the operative time was 550 and
480 minutes (P = .15); and the length of stay was 10 and 25 days (P = .38),
respectively. The BA group had a higher rate of intraoperative (P = .04) and
early (P = .02) overall complications. No significant difference was found in
early bowel (P = .15) or ureteral obstruction (P = .08), in the overall stomal
complications (P = .11), or in the rate of <90-day reoperation (P = .32).
CONCLUSION: A lower rate of intraoperative and postoperative complications
occurred in patients undergoing conversion of colostomy to a urinary diversion
compared with patients with de novo urinary conduit creation. When possible, a BA
should be avoided.
PMID- 28689779
TI - Urinary-cutaneous Fistulae Following Conservative Management of Extraperitoneal
Bladder Ruptures.
AB - OBJECTIVE: To evaluate our experience with urinary-cutaneous fistulae (UCFs) in
patients following conservative management of extraperitoneal bladder ruptures
(EBRs) caused by blunt trauma. MATERIALS AND METHODS: Patients with blunt-trauma
related EBR who underwent primary management with urethral catheter drainage
alone from 2000 to 2015 were identified in our institutional trauma registry. The
demographics, the hospital courses, and the outcomes of patients who developed
UCF were analyzed. RESULTS: A total of 96 patients with EBR were identified, of
which 56 (58%) were managed with urethral catheter drainage. 10 patients (18%)
developed major urologic complications including urosepsis (2), infected pelvic
hardware (1), persistent extravasation without cutaneous fistulization (1), and
UCF formation (6). Of the patients with UCF, the median time to diagnosis of EBR
was 1.5 days (range 0-12), whereas the median time to diagnosis of UCF was 11
days (range 3-31). Two patients developed UCF to the perineum, whereas 4
developed UCF to the thigh. Four (66.7%) underwent nonurologic operations without
cystorrhaphy before the development of UCF. One patient died without a resolution
of her fistula. The remaining 5 patients all required operative repair, with a
median time to repair from diagnosis of 21 days (range 2-106). The median time to
resolution from diagnosis was 64 days (range 35-155). CONCLUSION: UCFs are an
under-reported but morbid complication of the nonoperative management of EBR.
Although rare, UCF in this setting should prompt surgical intervention given the
potential for prolonged convalescence and a low probability of spontaneous
resolution.
PMID- 28689780
TI - [Author's reply to letter 'Adjusted morbidity groups: A pending debate'].
PMID- 28689781
TI - Erratum.
PMID- 28689782
TI - The microbiota and autoimmunity: Their role in thyroid autoimmune diseases.
AB - Since the 1970s, the role of infectious diseases in the pathogenesis of Graves'
disease (GD) has been an object of intensive research. The last decade has
witnessed many studies on Yersinia enterocolitica, Helicobacter pylori and other
bacterial organisms and their potential impact on GD. Retrospective, prospective
and molecular binding studies have been performed with contrary outcomes. Until
now it is not clear whether bacterial infections can trigger autoimmune thyroid
disease. Common risk factors for GD (gender, smoking, stress, and pregnancy)
reveal profound changes in the bacterial communities of the gut compared to that
of healthy controls but a pathogenetic link between GD and dysbiosis has not yet
been fully elucidated. Conventional bacterial culture, in vitro models, next
generation and high-throughput DNA sequencing are applicable methods to assess
the impact of bacteria in disease onset and development. Further studies on the
involvement of bacteria in GD are needed and may contribute to the understanding
of pathogenetic processes. This review will examine available evidence on the
subject.
PMID- 28689783
TI - Immune complexes containing malondialdehyde (MDA) LDL induce apoptosis in human
macrophages.
AB - Immune complexes (IC) containing predominantly malondialdehyde-LDL and the
corresponding autoantibodies (MDA-LDL IC) predict acute cardiovascular events,
while IC rich in oxidized LDL (oxLDL IC) predict cardiovascular disease
progression. Our objective was to determine mechanisms that could explain these
prognostic differences. We compared the effects of the interaction of oxLDL, MDA
LDL and the corresponding IC with human macrophages focusing on apoptosis,
metalloproteinases, and proinflammatory cytokines. MDA-LDL IC induced higher
degrees of apoptosis, higher levels of caspase-3 expression, and increased
expression and release of MMP-1 and TNF compared to MDA-LDL, oxLDL, and oxLDL IC.
The pro-apoptotic effects of MDA-LDL IC were inhibited by blocking TNFR 1 or
FcgammaRI. Blocking FcgammaRI abrogated the induction and expression of MMPs and
proinflammatory cytokines by MDA-LDL IC. In conclusion, the interaction of MDA
LDL IC with FcgammaRI triggers macrophage apoptosis and increased expression and
release of TNF and MMP-1, which can lead to the rupture of unstable plaques.
PMID- 28689784
TI - GEDOS-SECOT consensus on the care process of patients with knee osteoarthritis
and arthoplasty.
AB - OBJECTIVE: To develop recommendations on the evaluation and management procedure
in patients undergoing total knee replacement based on best evidence and the
experience of a panel of experts. METHODS: A multidisciplinary group of 12
experts was selected that defined the scope, users and the document parts. Three
systematic reviews were performed in patients undergoing knee replacement:
(i)efficacy and safety of fast-tracks; (ii)efficacy and safety of cognitive
interventions in patients with catastrophic pain, and (iii) efficacy and safety
of acute post-surgical pain management on post-surgical outcomes. A narrative
review was conducted on the evaluation and management of pain sensitization, and
about the efficacy and safety of pre-surgical physiotherapy. The experts
generated the recommendations and explicative text. The level of agreement was
evaluated in a multidisciplinary group of 85 experts with the Delphi technique.
The level of evidence was established as well for each recommendation. RESULTS: A
total of 20 recommendations were produced. An agreement higher than 80% was
reached in all of them. We found the highest agreement on the need for a full
discharge report, on providing proper information about the process and on
following available guidelines. CONCLUSIONS: There is consensus among
professionals involved in the management of patients undergoing total knee
replacement, in that it is important to protocolize the replacement process,
performing a proper, integrated and coordinated patient evaluation and follow-up,
paying special attention to the surgical procedure and postoperative period.
PMID- 28689785
TI - Effect of tranexamic acid administration on bleeding in primary total hip
arthroplasty.
AB - OBJECTIVE: To study the efficacy of tranexamic acid to decrease perioperative
bleeding in patients who have undergone a total hip arthroplasty operation and to
evaluate drug safety. MATERIAL AND METHODS: Observational, prospective,
controlled and randomized study on the efficacy of tranexamic acid as a method to
reduce bleeding in primary hip replacement surgery. We included 134 patients
operated during 2014 in our centre, who were divided into 2 groups according to
whether or not they had received tranexamic acid. The main study variables were
haemoglobin and haematocrit levels, the amount of blood collected from the post
operative drain in the first 12, 24 and 48hours and transfusion requirements.
RESULTS: Post-operative haemoglobin and haematocrit levels were statistically
higher (P<.001) in the group with treatment. During the first 48hours bleeding
values from the group that did not receive TAX were higher compared to patients
treated with tranexamic acid. Statistically significant differences (P=.001) were
found as to the need for transfusion according to group, more transfusions were
performed in the cohort that had not received tranexamic acid: 25.37% compared to
4.48% for the group with tranexamic acid. No adverse events related to
administration of tranexamic acid were recorded. CONCLUSIONS: Administration of
tranexamic acid has proved to be an effective and safe method to reduce peri
operative bleeding in patients who underwent total hip arthroplasty and avoids
allogenic blood transfusion. Therefore, tranexamic acid treatment could entail a
financial saving for the healthcare system and expose the patient to less risk.
PMID- 28689786
TI - Oxidative stress in bicuspid aortic valve-related aortopathy: Hand-me-downs and
yoga pants.
PMID- 28689787
TI - Dominoes: When a novel surgical approach creates new challenges.
PMID- 28689788
TI - Early trifecta valve failure: Warning shot or unfair scrutiny?
PMID- 28689789
TI - Postoperative atrial fibrillation: Can an ounce of prevention eliminate a pound
of cure?
PMID- 28689790
TI - Cell therapy and vocal fold scarring.
AB - Vocal fold microstructure is complex and can be affected by laryngeal
microsurgery, inducing scarring that prevents mechanical uncoupling of epithelium
and muscle, leading to vibration disorder and disabling dysphonia. Treatment
options presently are few, and often without efficacy for vibration, having only
an impact on volume to reduce glottal closure defect. The present review of the
literature had two aims: (i) to report the current state of the literature on
cell therapy in vocal fold scarring; and (ii) to analyze the therapeutic interest
of the adipose-derived stromal vascular fraction in the existing therapeutic
armamentarium. A PubMed(r) search conducted in September 2016 retrieved English
or French-language original articles on the use of stem cells to treat vocal fold
scarring. Twenty-seven articles published between 2003 and 2016 met the study
selection criteria. Mesenchymal stem cells were most widely used, mainly derived
from bone marrow or adipose tissue. Four studies were performed in vitro on
fibroblasts, and 18 in vivo on animals. End-points comprised: (i) scar analysis
(macro- and micro-scopic morphology, viscoelastic properties, extracellular
matrix, fibroblasts); and (ii) assessment of stem cell survival and
differentiation. The studies testified to the benefit of mesenchymal stem cells,
and especially those of adipose derivation. The stromal vascular fraction
exhibits properties that might improve results by facilitating production
logistics.
PMID- 28689791
TI - Peanut-specific type 1 regulatory T cells induced in vitro from allergic subjects
are functionally impaired.
AB - BACKGROUND: Peanut allergy (PA) is a life-threatening condition that lacks
regulator-approved treatment. Regulatory T type 1 (TR1) cells are potent
suppressors of immune responses and can be induced in vivo upon repeated antigen
exposure or in vitro by using tolerogenic dendritic cells. Whether oral
immunotherapy (OIT) leads to antigen-specific TR1 cell induction has not been
established. OBJECTIVES: We sought to determine whether peanut-specific TR1 cells
can be generated in vitro from peripheral blood of patients with PA at baseline
or during OIT and whether they are functional compared with peanut-specific TR1
cells induced from healthy control (HC) subjects. METHODS: Tolerogenic dendritic
cells were differentiated in the presence of IL-10 from PBMCs of patients with PA
and HC subjects pulsed with the main peanut allergens of Arachis hypogaea, Ara h
1 and 2, and used as antigen-presenting cells for autologous CD4+ T cells (CD4+ T
cells coincubated with tolerogenic dendritic cells pulsed with the main peanut
allergens [pea-T10 cells]). Pea-T10 cells were characterized by the presence of
CD49b+ lymphocyte-activation gene 3 (LAG3)+ TR1 cells, antigen-specific
proliferative responses, and cytokine production. RESULTS: CD49b+LAG3+ TR1 cells
were induced in pea-T10 cells at comparable percentages from HC subjects and
patients with PA. Despite their antigen specificity, pea-T10 cells of patients
with PA with or without OIT, as compared with those of HC subjects, were not
anergic and had high TH2 cytokine production upon peanut-specific restimulation.
CONCLUSIONS: Peanut-specific TR1 cells can be induced from HC subjects and
patients with PA, but those from patients with PA are functionally defective
independent of OIT. The unfavorable TR1/TH2 ratio is discussed as a possible
cause of PA TR1 cell impairment.
PMID- 28689793
TI - A single amino acid in MRGPRX2 necessary for binding and activation by
pruritogens.
PMID- 28689792
TI - Functional role of kynurenine and aryl hydrocarbon receptor axis in chronic
rhinosinusitis with nasal polyps.
AB - BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is associated with
mast cell-mediated inflammation and heightened oxidant stress. Kynurenine (KYN),
an endogenous tryptophan metabolite, can promote allergen-induced mast cell
activation through the aryl hydrocarbon receptor (AhR). OBJECTIVES: We sought to
determine the role of the KYN/AhR axis and oxidant stress in mast cell activation
and the development of CRSwNP. METHODS: We measured the expression of indoleamine
2,3-dioxygenase 1, tryptophan 2,3-dioxygenase, KYN, and oxidized calmodulin
dependent protein kinase II (ox-CaMKII) in nasal polyps and controls. KYN
potentiated ovalbumin (OVA)-induced ROS generation, cell activation, and ox
CaMKII expression were investigated in wild-type and AhR-deficient (AhR-/-) mast
cells. The role of ox-CaMKII in mast cell activation was further investigated.
RESULTS: Nasal polyps in CRSwNP showed an increased expression of indoleamine 2,3
dioxygenase 1, tryptophan2,3-dioxygenase, and KYN compared with controls. AhR was
predominantly expressed in mast cells in nasal polyps. Activated mast cells and
local IgE levels were substantially increased in eosinophilic polyps compared
with noneosinophilic polyps and controls. Furthermore, KYN potentiated OVA
induced ROS generation, intracellular Ca2+ levels, cell activation, and
expression of ox-CaMKII in wild-type, but not in AhR-/- mast cells. Compared with
noneosinophilic polyps and controls, eosinophilic polyps showed increased
expression of ox-CaMKII in mast cells. Mast cells from ROS-resistant CaMKII
MMVVdelta mice or pretreated with CaMKII inhibitor showed protection against KYN
promoted OVA-induced mast cell activation. CONCLUSIONS: These studies support a
potentially critical but previously unidentified function of the KYN/AhR axis in
regulating IgE-mediated mast cell activation through ROS and ox-CaMKII in CRSwNP.
PMID- 28689795
TI - Are e-cigarettes and tobacco products losing their allure for US teenagers?
PMID- 28689796
TI - Editorial.
PMID- 28689794
TI - Results from the 5-year SQ grass sublingual immunotherapy tablet asthma
prevention (GAP) trial in children with grass pollen allergy.
AB - BACKGROUND: Allergy immunotherapy targets the immunological cause of allergic
rhinoconjunctivitis and allergic asthma and has the potential to alter the
natural course of allergic disease. OBJECTIVE: The primary objective was to
investigate the effect of the SQ grass sublingual immunotherapy tablet compared
with placebo on the risk of developing asthma. METHODS: A total of 812 children
(5-12 years), with a clinically relevant history of grass pollen allergic
rhinoconjunctivitis and no medical history or signs of asthma, were included in
the randomized, double-blind, placebo-controlled trial, comprising 3 years of
treatment and 2 years of follow-up. RESULTS: There was no difference in time to
onset of asthma, defined by prespecified asthma criteria relying on documented
reversible impairment of lung function (primary endpoint). Treatment with the SQ
grass sublingual immunotherapy tablet significantly reduced the risk of
experiencing asthma symptoms or using asthma medication at the end of trial (odds
ratio = 0.66, P < .036), during the 2-year posttreatment follow-up, and during
the entire 5-year trial period. Also, grass allergic rhinoconjunctivitis symptoms
were 22% to 30% reduced (P < .005 for all 5 years). At the end of the trial, the
use of allergic rhinoconjunctivitis pharmacotherapy was significantly less (27%
relative difference to placebo, P < .001). Total IgE, grass pollen-specific IgE,
and skin prick test reactivity to grass pollen were all reduced compared to
placebo. CONCLUSIONS: Treatment with the SQ grass sublingual immunotherapy tablet
reduced the risk of experiencing asthma symptoms and using asthma medication, and
had a positive, long-term clinical effect on rhinoconjunctivitis symptoms and
medication use but did not show an effect on the time to onset of asthma.
PMID- 28689797
TI - Pudilan xiaoyan oral liquid alleviates LPS-induced respiratory injury through
decreasing nitroxidative stress and blocking TLR4 activation along with NF-KappaB
phosphorylation in mice.
AB - ETHNOPHARMACOLOGICAL RELEVANCE: Pudilan xiaoyan oral liquid (PDL), collected in
Chinese Pharmacopoeia, has been used clinically for treating inflammatory
diseases such as upper respiratory tract infection diseases. However, its
potential anti-inflammation and the mechanism are still unclear. MATERIALS AND
METHODS: lipopolysaccharide (LPS) was used to induce respiratory inflammation of
mice by intratracheal administration. UPLC/MS was performed for components
analysis of PDL. Enzyme-linked immune sorbent assay (ELISA) was conducted for
determining interleukin-6(IL-6), interleukin-1beta(IL-1beta) and tumor necrosis
factor-alpha(TNF-alpha) in serum and supernatant of tracheal tissue while Nitric
oxide assay kit for nitric oxide (NO) content. Hematoxylin-Eosin (HE) staining
was applied to evaluate pathological lesions. Western blotting analysis (WB) and
Immunohistochemistry(IHC) were employed for the determination of Toll-like
receptors 4(TLR4), TNF-alpha, IL-6, inducible nitric oxide synthase(iNOS) and
nuclear factor-kappa B p65 (NF-kappaB p65) protein expressions. RESULTS: Seven
major compounds of PDL were analyzed simultaneously. The treatment of PDL could
attenuate LPS-induced histopathological damage of tracheal tissues, followed by
reducing pro-inflammation mediators including TNF-alpha and IL-6 in serum and
supernatant of tracheal tissue. LPS-induced nitroxidative stress including NO
content and iNOS expression was inhibited significantly by PDL. Furthermore, PDL
also down-regulated NF-kB p65 phosphorylation and TLR4 expressions. CONCLUSION:
The results indicated that the PDL had a protective effect on LPS-induced
respiratory inflammation injury in mice. Our findings for the first time provide
experimental evidence for the application of PDL on respiratory inflammation
injury in clinical practice.
PMID- 28689798
TI - Ethyl acetate extract from Panax ginseng C.A. Meyer and its main constituents
inhibit alpha-melanocyte-stimulating hormone-induced melanogenesis by suppressing
oxidative stress in B16 mouse melanoma cells.
AB - ETHNOPHARMACOLOGICAL RELEVANCE: Hyperpigmentation disease involves darkening of
the skin color due to melanin overproduction. Panax ginseng C.A. Meyer is a well
known traditional Chinese medicine and has a long history of use as a skin
lightener to inhibit melanin formation in China, Korea and some other Asian
countries. However, the constituents and the molecular mechanisms by which they
affect melanogenesis are not fully clear. AIM OF THE STUDY: The purpose of this
study was to identify the active ingredient in Panax ginseng C.A. Meyer extract
that inhibits mushroom tyrosinase activity and to investigate the antioxidative
capacity and molecular mechanisms of the effective extract on melanogenesis in
B16 mouse melanoma cells. MATERIALS AND METHODS: Aqueous extracts of Panax
ginseng C.A. Meyer were successively fractionated with an equal volume of
chloroform, ethyl acetate, and n-butyl alcohol to determine the effects by
examining the activity of mushroom tyrosinase. The effective fraction was
analyzed using HPLC and LC-MS. The antioxidative capacity and the inhibitory
effects on melanin content, cell intracellular tyrosinase activity, and
melanogenesis protein levels were determined in alpha-melanocyte-stimulating
hormone (alpha-MSH)-treated B16 mouse melanoma cells. RESULTS: The ethyl acetate
extract from Panax ginseng C.A. Meyer (PG-2) had the highest inhibiting effect on
mushroom tyrosinase, mainly contained phenolic acids, including protocatechuic
acid, vanillic acid, p-coumaric acid, salicylic acid, and caffeic acid, and
exhibited apparent antioxidant activity in vitro. PG-2 and its main constituents
significantly decreased melanin content, suppressed cellular tyrosinase activity,
and reduced expression of tyrosinase protein to inhibit B16 cells melanogenesis
induced by alpha-MSH, and no cytotoxic effects were observed. They also inhibited
cellular reactive oxygen species (ROS) generation, increased superoxide dismutase
(SOD) activity and glutathione (GSH) level in alpha-MSH-treated B16 cells
effectively. And those activities of its main constituents could reach more than
80% of PG-2. The ROS scavengers N-acetyl-L-cysteine (NAC) had a similar
inhibitory effect on melanogenesis. CONCLUSIONS: These results suggest that ethyl
acetate extract from Panax ginseng C.A. Meyer has the highest effect on
inhibiting melanogenesis, and that its main components are polyphenolic
compounds, which may inhibit melanogenesis by suppressing oxidative stress. This
work provides new insight into the active constituents and molecular mechanisms
underlying skin-lightening effect of Panax ginseng C.A. Meyer.
PMID- 28689799
TI - Cardioprotective effects of Viscum album L. subsp. album (European misletoe) leaf
extracts in myocardial ischemia and reperfusion.
AB - ETHNOPHARMACOLOGICAL RELEVANCE: Viscum album L. (European mistletoe) is a
hemiparasitic plant belonging to Loranthaceae family and has been used in Turkish
traditional medicine for the treatment of cardiovascular disorders and heart
diseases such as hypertension, tachycardia and angina pectoris. AIM OF THE STUDY:
The present study investigated the cardioprotective effects of V. album leaf
extracts in myocardial ischemia and reperfusion injury in rats. MATERIAL AND
METHODS: Lyophilized aqueous (AVa) and methanolic (MVa) extracts of V. album were
prepared from dried leaf. The isolated hearts were perfused with V. album
extracts prior to and during 35min of ischemia induced by coronary artery
occlusion. After 120min of coronary reperfusion, infarct size was determined by
triphenyltetrazolium staining. RESULTS: Both AVa and MVa extracts reduced the
extent of infarction compared with untreated control hearts, but protective
effect of MVa had more potential in low concentration; infarct size as proportion
of ischemic risk zone: AVa 17.5+/-1.5%; Mva 20.3+/-2.5%, both P<0.01 versus
control 38.1+/-1.4%. This protective effect was comparable to infarct limitation
induced by ischemic preconditioning (21.5+/-2.4%). Inhibition of nitric oxide
synthesis with L-NG-nitroarginine methyl ester completely abrogated the
protection afforded by both extracts. ATP-sensitive K+ channel blockade by
glibenclamide abrogated the protection afforded by MVa while attenuating, but not
abolishing, the protective action of Ava. CONCLUSIONS: This study provided the
first experimental evidence that V. album leaf extracts can mediate nitric oxide
dependent cardioprotection against myocardial injury produced by
ischemia/reperfusion insult. With this study, popular usage of V. album extracts
in Turkish folk medicine as a remedy for cardiac diseases was justified.
PMID- 28689800
TI - Investigation and analysis of the characteristics and drug sensitivity of
bacteria in skin ulcer infections.
AB - PURPOSE: Skin ulcer is a common type of disease affecting patients' health and
quality of life, and bacterial infection increases the difficulty of its
management. METHODS: The present study collected the results of bacterial culture
sampled from the surface of 110 cases of skin ulcers at our hospital from January
2011 to December 2012. We analyzed the constituent ratios of ulcer surface
bacteria, the change in the main infectious bacteria and the results of drug
sensitivity testing for common bacteria. In addition, the characteristics of
bacterial infection of skin ulcers were summarized. RESULT: Of the 110 samples,
90 isolated bacteria were cultured. Sixty-one were Gram-negative bacteria, mainly
comprising Pseudomonas aeruginosa, Klebsiella pneumoniae, Enterobacter cloacae
and Escherichia coli. In addition, 23 isolates were Gram-positive bacteria,
mainly comprising Staphylococcus aureus and Enterococcus faecalis. The
probability of a negative bacterial culture in 2012 was significantly lower than
that in 2011 (16.7% vs. 40.0%, p < 0.01). Moreover, the probability of P.
aeruginosa infection in 2012 was significantly higher than that in 2011 (31.7%
vs. 14.0%, p < 0.01). P. aeruginosa was resistant to seven commonly used
antibiotics. Both K. pneumoniae and E. coli had higher resistance to ampicillin.
E. cloacae were not sensitive to piperacillin/tazobactam. Acinetobacter baumannii
was resistant to all the tested drugs. S. aureus, E. faecalis and Staphylococcus
epidermidis had high resistance to clindamycin. There was other drug resistance
to reflect the higher rate of skin bacterial resistance. CONCLUSION: Skin
bacterial resistance rate is high. Gram-negative bacteria gradually account for
the majority, and P. aeruginosa becomes the most important skin infection
pathogen. These characteristics of bacterial infections of skin ulcers provide a
significant reference for guiding the selection of antibiotics, better
controlling infections of skin ulcers and accelerating the healing of skin
ulcers.
PMID- 28689801
TI - A systematic review of the effect of various interventions on reducing fatigue
and sleepiness while driving.
AB - PURPOSE: To identify and appraise the published studies assessing interventions
accounting for reducing fatigue and sleepiness while driving. METHODS: This
systematic review searched the following electronic databases: Medline, Science
direct, Scopus, EMBASE, PsycINFO, Transport Database, Cochrane, BIOSIS, ISI Web
of Knowledge, specialist road injuries journals and the Australian Transport and
Road Index database. Additional searches included websites of relevant
organizations, reference lists of included studies, and issues of major injury
journals published within the past 15 years. Studies were included if they
investigated interventions/exposures accounting for reducing fatigue and
sleepiness as the outcome, measured any potential interventions for mitigation of
sleepiness and were written in English. Meta-analysis was not attempted because
of the heterogeneity of the included studies. RESULTS: Of 63 studies identified,
18 met the inclusion criteria. Based on results of our review, many interventions
in the world have been used to reduce drowsiness while driving such as behavioral
(talking to passengers, face washing, listening to the radio, no alcohol use,
limiting the driving behavior at the time of 12 p.m. - 6 a.m. etc), educational
interventions and also changes in the environment (such as rumble strips,
chevrons, variable message signs, etc). Meta-analysis on the effect of all these
interventions was impossible due to the high heterogeneity in methodology, effect
size and interventions reported in the assessed studies. CONCLUSION: Results of
present review showed various interventions in different parts of the world have
been used to decrease drowsy driving. Although these interventions can be used in
countries with high incidence of road traffic accidents, precise effect of each
intervention is still unknown. Further studies are required for comparison of the
efficiency of each intervention and localization of each intervention according
to the traffic patterns of each country.
PMID- 28689802
TI - Comparison of phenotypic and global gene expression changes in Xenopus tropicalis
embryos induced by agonists of RAR and RXR.
AB - Retinoic acid functions through two classes of receptors, i.e., the retinoic acid
receptor (RAR) and the retinoid X receptor (RXR). The difference in the role
between RAR and RXR, however, are not well clarified. In the present study, we
comparatively investigated the phenotypic and global gene expression changes in
Xenopus tropicalis embryos induced by three different agonists, including a RAR
selective ligand (all-trans retinoic acid, at-RA), a RXR selective ligand
(fluorobexarotene, FBA) and their common ligand (9-cis retinoic acid, 9c-RA). All
three agonists induced striking and similar malformations in X. tropicalis
embryos at the concentrations of 5-50MUg/L. Especially, the development of
anterior structures and caudal region was dramatically altered. The hierarchical
clustering analysis of phenotypes and gene profiles suggested that effects
induced by 9c-RA separated from those by at-RA and FBA. The up-regulated genes
were involved in multiple pathways while down-regulated genes were mainly related
to phototransduction and tyrosine metabolism. at-RA primarily affected the
retinol, glycolysis, starch and sucrose metabolisms while FBA led to disturbances
in more wide-ranging pathways such as the PPAR, adipocytokine, insulin, FoxO
signaling pathways, alanine, aspartate and glutamate metabolism. RXR is a
heterodimeric partner for several other nuclear receptors, which opens the
possibility that additional retinoid effects could be mediated by FBA, such as
RXR-PPAR. Our data indicates that not only RXR-RAR but also RXR-PPAR plays
important roles in the control of metabolism with retinoid treatment in X.
tropicalis embryos.
PMID- 28689803
TI - Lipopolysaccharides induce Smad2 phosphorylation through PI3K/Akt and MAPK
cascades in HSC-T6 hepatic stellate cells.
AB - AIMS: Endotoxemia and its pro-fibrogenic signaling play a significant role in the
development of hepatic fibrosis. This study investigated whether
lipopolysaccharide (LPS) directly activate cultured HSC-T6 hepatic stellate cells
(HSCs) through triggering Smad-dependent pro-fibrogenic signaling pathway. MAIN
METHODS: Direct cell counting and assays for cell proliferation and migration
were used to measure the effects of LPS on HSC behaviors. Quantitative PCR,
Western blot, and gelatin zymography were used to quantify the molecular effects
of LPS on expression of HSC activation markers and signaling activity. KEY
FINDINGS: Long-term exposure to LPS exhibited moderately stimulatory effect on
HSC cell growth. A wound-healing cell migration assay showed that LPS suppressed
HSC-T6 cell migration. qPCR and Western blotting detection indicated that LPS
treatment induced upregulation of type I and IV collagens, alpha-smooth muscle
actin (alpha-SMA), and matrix metalloproteinase-9 (MMP-9). Gelatin zymography
confirmed that LPS elevated MMP-9, but not MMP-2 gelatinolytic activity.
Moreover, LPS immediately stimulated Akt, EKR1/2, JNK, p38 MAPK, and Smad2
hyperphosphorylation, supporting that LPS directly triggers pro-fibrogenic Smad
signaling cascade without TGF-beta1 stimulation. Kinase blockade experiments
demonstrated the involvement of PI3K/Akt, JNK, p38 MAPK, but not ERK1/2 signaling
activation in the LPS-elicited Smad2 phosphorylation as well as the
overexpression of type I collagen and alpha-SMA in HSC-T6 cells. SIGNIFICANCE:
These findings demonstrate that LPS exerts pro-fibrogenic effect through
activation and transformation of HSCs. The tissue-remodeling effect of LPS may be
attributable to its ability to activate non-canonical Smad pathway through
PI3K/Akt and MAPK signaling cascades.
PMID- 28689804
TI - Efficacy and safety of levosimendan in patients with acute right heart failure: A
meta-analysis.
AB - AIMS: Right heart failure (RHF), which is caused by a variety of heart and lung
diseases, has a high morbidity and mortality rate. Levosimendan is a cardiac
inotropic drug and vasodilator. The effect of levosimendan on RHF remains
unclear. We sought to evaluate the efficacy and safety of levosimendan in
patients with acute RHF. MATERIALS AND METHODS: We systematically searched
PubMed, Cochrane Library, EMBASE, and ClinicalTrials.gov to identify studies
reporting the efficacy and safety of levosimendan for the treatment of RHF. KEY
FINDINGS: Ten trials, including 359 participants from 6 RCTs and 4 self
controlled trials, were evaluated. In the 6 RCTs, we found that patients treated
with levosimendan for 24h showed a significant increase in tricuspid annular
plane systolic excursion [1.53; 95% CI (0.54, 2.53); P=0.002] and ejection
fraction [3.59; 95% CI (1.21, 5.98); P=0.003] as well as a significant reduction
in systolic pulmonary artery pressure [-6.15; 95% CI (-9.29, -3.02); P=0.0001]
and pulmonary vascular resistance [-39.48; 95% CI (-65.59, -13.38); P=0.003],
whereas changes in mean pulmonary pressure were nonsignificant. Adverse events
did not significantly differ between the two groups. SIGNIFICANCE: Our study
shows that levosimendan exhibits short-term efficacy for treating RHF in patients
with a variety of heart and lung diseases. Additional strict multicentre RCTs
with long follow-up times and large sample sizes are required to further validate
the efficacy and safety of this treatment.
PMID- 28689805
TI - The importance of folate, vitamins B6 and B12 for the lowering of homocysteine
concentrations for patients with recurrent pregnancy loss and MTHFR mutations.
AB - In patients with MTHFR (methylenetetrahydrofolate reductase) mutations and
hyperhomocysteinemia, recurrent pregnancy loss is a frequent feature. The aim of
the study was to evaluate the impact of folic acid, vitamins B6 and B12
supplementation for the lowering of total homocysteine concentrations and
pregnancy. 16 patients who had had 3 or more miscarriages and MTHFR mutations
were used in the study. They received methylfolate (5mg/day), vitamin B6
(50mg/day) and vitamin B12 (1mg/week). Supplementation induced a decrease in
homocysteine from 19.4+/-5.3MUmol/L to 6.9+/-2.2MUmol/L after folate
supplementation (p<0.05). During one year 7 women became pregnant and delivered.
Two women delivered from the homozygous C677T mutations group (7 patients) and
combined heterozygous C677T/A1298C mutations group (5 patients), while 3
deliveries were in A1298C homozygous mutations group (4 patients). In conclusion,
supraphysiologic methylfolate, vitamins B6 and B12 supplementation in woman with
MTHFR mutations has a beneficial effect on pregnancy outcome.
PMID- 28689806
TI - Cigarette smoke impaired maturation of ovarian follicles and normal growth of
uterus inner wall of female wild-type and hypertensive rats.
AB - Cigarette smoke (CS) is well known to be very harmful to human body functions
such as fertility, reproduction, and development. CS is considered to more affect
patients with hypertension (HT). To estimate the effect of CS associated with
female rat's fertility, we examined the histopathological characteristics of the
uterus and ovary which were obtained from the female rats exposed to smoke of the
standard cigarette (3R4F) for 4 weeks (10h a week) according to the OECD
guidelines. The female wild-type Wistar Kyoto (WK) rats (WTR) and spontaneously
hypertensive WK rats (SHR) were used to compare the effect of CS on healthy and
hypertensive rats. After CS exposure, we manufactured tissue slides from uterine
and ovarian samples and evaluated the maturation of follicles of ovary and cell
proliferation in the uterus by H&E staining and immunohistochemistry (IHC). In
IHC analysis on ovarian tissues, the expression of proliferating cell nuclear
antigen (PCNA) and the number of follicles were decreased by CS exposure. On the
contrary, PCNA expression and cell proliferation in the uterine inner layers were
increased by CS exposure. The protein expression of C/EBP homologous protein
(CHOP), an endoplasmic reticulum (ER)-stress marker, and BAX, a pro-apoptotic
protein, was decreased by CS exposure. This phenomenon was more exacerbated in
SHR rats than in WTR rats. Taken together, acute exposure to CS induced the
decreased maturation of ovarian follicles and abnormal over-growth of uterine
inner wall, leading to a harmful effect on female rat's normal function. In
addition, this harmful effect of CS may be displayed more seriously in rats with
HT.
PMID- 28689807
TI - Rewriting the tip apex distance for the proximal femoral nail anti-rotation.
AB - INTRODUCTION: The proximal femur nail anti-rotation (PFNA-II) (Synthes GmbH,
Oberdorf, Switzerland) is the most commonly used implant for intramedullary
nailing of unstable intertrochanteric fractures in our centre. However,
mechanical failure of the bone with respect to the implant is a cause of concern
due to its significant morbidity especially in the elderly. To date, factors for
fixation failures are not well defined in the literature. This study aims to
evaluate the factors that predispose to cut out of the PFNA implant and to
provide a guide for surgical fixation. PATIENTS AND METHODS: This study was a
retrospective analysis of 340 patients who underwent PFNA-II insertion from 2011
to 2013 in our centre. Intraoperative image intensifier images were used for
calculation of tip apex distance, neck shaft angles, determination of Cleveland
zones. Demographic data was collected on patients age and gender. The fractures
were classified based on AO-OTA classification (Marsh et al., 2007) [1]. Patients
were followed up for a minimum of 4 months and union of the fracture or until a
complication occurred. Risk ratio for cut out was also compared with each
statistically significant variable to determine the cut-off point. RESULTS: The
incidence of cut out was 6.7% Tip apex distance, neck shaft angles and female
gender were statistically significant for cut out. The study found that tip apex
distance beyond 27mm increased the risk of cut out. Neck shaft angles less than
128 degrees also increased the risk of cut out. Posterior and superior blade
position in the femoral head and AO 31A3 fractures trended towards significance
for cut out but were not statistically significant. CONCLUSION: To avoid cut out,
one should aim for a tip apex distance of not more than 27mm and preserve a neck
shaft angle of more than 128 degrees . Risk stratification of the patient allows
the surgeon to take greater caution in the post-operative period to detect early
cut out.
PMID- 28689808
TI - Effectiveness of sonography assisted minimal invasive plate osteosynthesis (MIPO)
compare with fluoroscope assisted in femoral shaft fracture: A cadaveric study.
AB - INTRODUCTION: A minimal invasive plate osteosynthesis (MIPO) has an advantage of
biological soft tissue preservation that consists of preserving bony blood
supply, fracture hematoma and less soft tissue damage which leads to decreasing
of infection rate and rapid bone healing. However, the radiation exposure is
still a disadvantage of this technique. A sonography that provides dynamic real
time imaging may be used as an alternative technique for assisting MIPO. The aim
of this study was to compare the effectiveness of MIPO in femoral shaft fracture
between the sonography assisted and the fluoroscopy assisted. METHODS: Twenty
eight cadaveric limbs were subjected to create femoral shaft fracture. Then,
sonography assisted reduction with temporary external fixation and MIPO were
performed. Images of the sonography and the fluoroscopy were recorded including
before reduction, after reduction and after MIPO in order to identify fracture
displacements in anteroposterior and mediolateral directions. Moreover, the
anterior and posterior distances from edge of the bone to the plate were measured
to confirm plate position. The effectiveness of this technique was defined as the
proper plate position and acceptable alignment after fixation. All distances from
the sonography and the fluoroscopy were also analyzed and compared using Pearson
correlation and Bland-Altman method to assess the agreements between two tests.
RESULT: All of the subjects were met the criteria for acceptable alignment. We
found only three femoral shaft fracture (11%) operated with MIPO by sonography
assisted that showed slipped plate off femoral bones. According to Pearson
correlation, there were good to excellent agreements in term of measuring
fracture displacement before (Pearson Correlation >0.7) and after reduction
(Pearson Correlation >0.7) between these two tests. There was moderate agreement
regarding to evaluation of plate position (Pearson Correlation 03.-0.7). When we
compared two methods of measurement using Bland-Altman plot, there were no
statistical significant difference (P<0.05). CONCLUSION: Images from the
sonography could provide visualization of the fracture during reduction and MIPO
as accurately as the radiography. Thus, the sonography assisted MIPO in femoral
shaft fracture can be done effectively comparing with radiographic assisted.
PMID- 28689809
TI - Editorial overview: Biotic interactions: Inferring global implications for the
molecular interface between plants and their biotic interactions across scales.
PMID- 28689810
TI - LincRNA-p21 knockdown enhances radiosensitivity of hypoxic tumor cells by
reducing autophagy through HIF-1/Akt/mTOR/P70S6K pathway.
AB - Hypoxic conditions are common in solid tumors and have a significant effect on
tumor progression, therapeutic and prognosis. Long noncoding RNAs (lncRNAs) are
longer than 200 nucleotides and cannot be translated into proteins, which play
important roles in some diseases including cancer. Although previous analysis
have showed that long intergenic non-coding RNA (lincRNA)-p21 is hypoxia
responsive and functions as a new regulator of cell cycle, apoptosis and warburg
effect in cervical cancer, its biological roles in hypoxic hepatoma and glioma
are unknown. In this work, we found that X-ray irradiation or hypoxia treatment
elevated lincRNA-p21 expression in SMMC7721 hepatoma and U251MG glioma cells.
Knockdown of lincRNA-p21 induced G2/M phase arrest, promoted apoptosis, decreased
cell proliferation and motility, and reduced autophagy through HIF
1/Akt/mTOR/P70S6K pathway in hypoxic tumor cells. Our results delineated a novel
mechanism of lincRNA-p21 in enhancing hypoxic tumor cell radiosensitivity, which
might provide valuable targets for radiation therapy for solid tumors, such as
hepatoma and glioma.
PMID- 28689811
TI - AMPK activation ameliorates D-GalN/LPS-induced acute liver failure by
upregulating Foxo3A to induce autophagy.
AB - BACKGROUND AND AIM: Acute liver failure (ALF) is an uncommon but serious disease
still carrying a high mortality. This study aimed to investigate the mechanism of
AMPK on D-GalN/LPS-induced ALF. METHODS: In this study, we utilized
intraperitoneal injection of D-GalN/LPS to induce ALF model, and analyzed the
expression of AMPK, inflammatory cytokines (TNF-alpha, IL-1beta and IL-6), Foxo3A
and autophagy-related genes (Atg-5, Beclin-1, Atg-7) by real-time quantitative
polymerase chain reaction (RT-PCR) in liver tissue. We also examined the level of
alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum of
ALF mice. AMPK activation and inhibition of autophagy were induced by AICAR and 3
MA, respectively. Silence and overexpression of Foxo3A were performed by si
Foxo3A and pcDNA-Foxo3A, respectively. Lastly, the BMDM-conditioned medium (BMDM
CM) derived from BMDMs treated with AICAR and LPS were used to explore the effect
of AMPK and Foxo3A on hepatocytes. RESULT: The expression of AMPK was decreased
in liver tissue and the level of ALT and AST were increased in serum of D
GalN/LPS-induced ALF mice. AMPK activation ameliorated ALF by inhibiting
inflammation (downregulated TNF-alpha, IL-1beta and IL-6 expression), activating
autophagy (increased Atg-5, Beclin-1 and Atg-7 expression) and upregulating
Foxo3A expression. Silence of Foxo3A decreased AMPK-activated autophagy, but
overexpressing Foxo3A attenuated liver failure by activating autophagy. In
addition, AMPK activation alleviated liver failure in vitro. CONCLUSION: Thus,
AMPK/Foxo3A/autophagy pathway may be an effective treatment approach to
ameliorate ALF.
PMID- 28689812
TI - IBMX protects human proximal tubular epithelial cells from hypoxic stress through
suppressing hypoxia-inducible factor-1alpha expression.
AB - Hypoxia predisposes renal fibrosis. This study was conducted to identify novel
approaches to ameliorate the pathogenic effect of hypoxia. Using human proximal
tubular epithelial cells we showed that a pan-phosphodiesterase (PDE) inhibitor,
3-isobutyl-1-methylxanthine (IBMX) dose and time dependently downregulated
hypoxia-inducible factor 1alpha (HIF-1alpha) mRNA expression, which was further
augmented by addition of a transcriptional inhibitor, actinomycin D. IBMX also
increased the cellular cyclic adenosine monophosphate (cAMP) level. Luciferase
assay showed that blocking of protein kinase A (PKA) using H89 reduced, while 8
Br-cAMP agonized the repression of HIF-1alpha promoter activity in hypoxic
condition. Deletion of cAMP response element binding sites from the HIF-1alpha
promoter abrogated the effect of IBMX. Western blot and immunofluorescent study
confirmed that the CoCl2 induced increased HIF-1alpha protein in whole cell
lysate and in nucleus was reduced by the IBMX. Through this process, IBMX
attenuated both CoCl2 and hypoxia induced mRNA expressions of two pro-fibrogenic
factors, platelet-derived growth factor B and lysyl oxidase. Moreover, IBMX
reduced production of a mesenchymal transformation factor, beta-catenin; as well
as protected against hypoxia induced cell-death. Taken together, our study showed
novel evidence that the PDE inhibitor IBMX can downregulate the transcription of
HIF-1alpha, and thus may attenuate hypoxia induced renal fibrosis.
PMID- 28689813
TI - Combination of commercially available molecular assays and culture based methods
in diagnosis of tuberculosis and drug resistant tuberculosis.
AB - Early diagnosis of tuberculosis is of major clinical importance. Among 4733
clinical specimens collected from 3363 patients and subjected to Ziehl-Neelsen
microscopy, 4109 were inoculated onto Lowenstein-Jensen slants and 3139 in
Bactec/9000MB. Polymerase Chain Reaction (PCR) was performed in 3139 specimens,
whereas, a genotypic assay was directly applied in 93 Mycobacterium tuberculosis
complex PCR-positive for isoniazid and rifampicin resistance detection specimens
(GenoType MTBDRplus). Recovered M. tuberculosis isolates (64) as well as, 21 more
sent from Regional Hospitals were tested for antimycobacterial resistance with a
phenotypic (manual MGIT-SIRE) and a genotypic assay (GenoType MTBDRplus). PCR in
the clinical specimens showed excellent specificity (97.4%) and accuracy (96.8%),
good sensitivity (70.4%), but low positive predictive value (40.3%). MGIT-SIRE
performed to M. tuberculosis did not confer a reliable result in 16 isolates. Of
the remaining 69 isolates, 15 were resistant to streptomycin, seven to isoniazid,
seven to ethambutol and five to rifampicin. GenoType MTBDRplus correctly detected
isoniazid (seven) and rifampicin-resistant M. tuberculosis strains (five),
showing an excellent performance overall (100%). Susceptibility results by the
molecular assay applied directly to clinical specimens were identical to those
obtained from recovered isolates of the corresponding patients. Combining
molecular and conventional methods greatly contribute to early diagnosis and
accurate susceptibility testing of tuberculosis.
PMID- 28689814
TI - Isolation and characterization of a novel endo-beta-1,4-glucanase from a
metagenomic library of the black-goat rumen.
AB - The various types of lignocellulosic biomass found in plants comprise the most
abundant renewable bioresources on Earth. In this study, the ruminal microbial
ecosystem of black goats was explored because of their strong ability to digest
lignocellulosic forage. A metagenomic fosmid library containing 115,200 clones
was prepared from the black-goat rumen and screened for a novel cellulolytic
enzyme. The KG35 gene, containing a novel glycosyl hydrolase family 5 cellulase
domain, was isolated and functionally characterized. The novel glycosyl hydrolase
family 5 cellulase gene is composed of a 963-bp open reading frame encoding a
protein of 320 amino acid residues (35.1kDa). The deduced amino acid sequence
showed the highest sequence identity (58%) for sequences from the glycosyl
hydrolase family 5 cellulases. The novel glycosyl hydrolase family 5 cellulase
gene was overexpressed in Escherichia coli. Substrate specificity analysis
revealed that this recombinant glycosyl hydrolase family 5 cellulase functions as
an endo-beta-1,4-glucanase. The recombinant KG35 endo-beta-1,4-glucanase showed
optimal activity within the range of 30-50 degrees C at a pH of 6-7. The
thermostability was retained and the pH was stable in the range of 30-50 degrees
C at a pH of 5-7.
PMID- 28689815
TI - Nicotine promotes blood retinal barrier damage in a model of human diabetic
macular edema.
AB - More than 1 billion world's population actively smokes tobacco containing the
bioactive component nicotine (NT). The biological role of this molecule is
mediated through the activation of nicotinic cholinergic receptors, widely
distributed in various human tissues including retinal pigmented epithelium. The
long-term assumption of NT contributes to several diseases development such as
diabetic retinopathy. The major complication of this pathology is the diabetic
macular edema (DME), characterized by macular area thinning and blood-retinal
barrier (BRB) breakdown. Retinal hyperglycemic/hypoxic microenvironment
represents one of the main factors favoring DME progression by eliciting the
hypoxia-inducible factors (HIFs) expression. The latter induce new vessels
formation by stimulating cellular secretion of vascular endothelial growth factor
(VEGF). The etiology of DME is multifactorial, but little is known about the risk
factors linked to cigarette smoking, in particular to nicotine's contribution. In
the present study, we have investigated the NT role in a model, in vitro, of DME,
by evaluating its effect on outer BRB permeability and HIFs/VEGF expression
following exposure to hyperglycemic/hypoxic insult. Our results have demonstrated
that this compound alters outer BRB integrity exposed to high glucose and low
oxygen pressure microenvironment by upregulating HIF-1alpha/HIF-2alpha, VEGF
expression and ERK1/2 phosphorylation. These data have suggested that NT may play
a negative role in active smokers affected by DME.
PMID- 28689817
TI - Length of time domestic dogs (Canis familiaris) spend smelling urine of
gonadectomised and intact conspecifics.
AB - Domestic dogs (Canis familiaris) use urine to communicate among themselves,
however, it is unknown whether the gonadectomy (neutering or spaying) of a dog
affects this communication in anyway. Urine samples from 10 intact and 10
gonadectomised, unfamiliar dogs were presented to 12 tester dogs to sniff under
controlled conditions in a pilot study. The amount of time the tester dogs spent
sniffing each sample was recorded. Overall, tester dogs were recorded smelling
the urine of gonadectomised individuals for a longer time. In addition to the
type of urine sample, the result is likely to have been influenced by the sex and
status (gonadectomised or intact) of the tester dogs. The observed increase in
the length of time spent sniffing urine from gonadectomised individuals could be
explained by the tester dogs experiencing more difficulty in gaining information
from the urine or facing more confusion while analysing the urine compared to the
intact urine they have evolved to smell.
PMID- 28689816
TI - A novel role for dopamine signaling in the pathogenesis of bone loss from the
atypical antipsychotic drug risperidone in female mice.
AB - Atypical antipsychotic (AA) drugs, including risperidone (RIS), are used to treat
schizophrenia, bipolar disorder, and autism, and are prescribed off-label for
other mental health issues. AA drugs are associated with severe metabolic side
effects of obesity and type 2 diabetes. Cross-sectional and longitudinal data
also show that risperidone causes bone loss and increases fracture risk in both
men and women. There are several potential mechanisms of bone loss from RIS. One
is hypogonadism due to hyperprolactinemia from dopamine receptor antagonism.
However, many patients have normal prolactin levels; moreover we demonstrated
that bone loss from RIS in mice can be blocked by inhibition of beta-adrenergic
receptor activation with propranolol, suggesting the sympathetic nervous system
(SNS) plays a pathological role. Further, when, we treated ovariectomized (OVX)
and sham operated mice daily for 8weeks with RIS or vehicle we demonstrated that
RIS causes significant trabecular bone loss in both sham operated and OVX mice.
RIS directly suppressed osteoblast number in both sham and OVX mice, but
increased osteoclast number and surface in OVX mice alone, potentially accounting
for the augmented bone loss. Thus, hypogonadism alone cannot explain RIS induced
bone loss. In the current study, we show that dopamine and RIS are present in the
bone marrow compartment and that RIS can exert its effects directly on bone cells
via dopamine receptors. Our findings of both direct and indirect effects of AA
drugs on bone are relevant for current and future clinical and translational
studies investigating the mechanism of skeletal changes from AA drugs.
PMID- 28689818
TI - The Year in Thoracic Anesthesia: Selected Highlights from 2016.
PMID- 28689819
TI - Prediction, Guidance, and the Utility of Information.
PMID- 28689820
TI - Reverse total shoulder glenoid baseplate stability with superior glenoid bone
loss.
AB - BACKGROUND: Superior wear of the glenoid bone is common in patients with rotator
cuff arthropathy. This can become a treatment challenge for patients who require
shoulder arthroplasty. In reverse shoulder arthroplasty (RSA), glenoid bone loss
may affect the stability of baseplate fixation. The primary purpose of this
biomechanical laboratory study was to assess the initial fixation stability of
RSA glenosphere baseplates in the presence of variable amounts of superior
glenoid bone loss. MATERIALS AND METHODS: High-density solid rigid polyurethane
foam (30 pounds/cubic foot) was machined to model the glenoid with variable
superior defects that provided different levels of support (100%, 90%, 75%, and
50%) for the glenosphere baseplate. The samples were cyclically loaded (0-750 N
at 1 Hz for 5000 cycles) at a 60 degrees glenohumeral angle. The micromotion and
migration of the baseplate were calculated from displacement data captured during
the loading tests with an array of 3 linear variable differential transformers
mounted around the baseplate. RESULTS: Micromotion was significantly greater in
samples with 50% defects compared with those with smaller defects. Migration was
significantly greater after testing for all defect sizes. CONCLUSIONS: Initial
fixation of RSA glenosphere baseplates was significantly reduced in models with
50% bone loss on the superior edge compared with models with less bone loss in
this high-density bone foam model.
PMID- 28689821
TI - Role of the lateral collateral ligament in posteromedial rotatory instability of
the elbow.
AB - BACKGROUND: Posteromedial rotatory instability (PMRI) of the elbow consists of an
anteromedial coronoid fracture with lateral collateral ligament (LCL) and
posterior bundle of the medial collateral ligament (PMCL) tears. We hypothesized
that the LCL tear is required for elbow subluxation/joint incongruity and that an
elbow affected by an anteromedial subtype 2 coronoid fracture and a PMCL tear
exhibits contact pressures different from both an intact elbow and an elbow
affected by PMRI. MATERIALS AND METHODS: Six cadaveric elbows were tested under
gravity varus stress using a custom-made machine designed to simulate muscle
loads and to passively flex the elbow from 0 degrees to 90 degrees and measure
joint contact pressures. After testing of the intact specimen (INTACT-elbow), an
anteromedial subtype 2 coronoid fracture with a PMCL tear (COR+PMCL-elbow) and a
PMRI injury (PMRI-elbow), after adding an LCL tear, were tested. The highest
values of mean contact pressure were used for the comparison among the 3 groups.
RESULTS: Neither subluxation nor joint incongruity was observed in the COR+PMCL
elbow. The addition of an LCL detachment consistently caused subluxation and
joint incongruity. Mean contact pressures were higher in the COR+PMCL-elbow
compared with the INTACT-elbow (P < .03) but lower than in the PMRI-elbow (P <
.001). CONCLUSIONS: The LCL lesion in PMRI is necessary for elbow subluxation and
causes marked elevations in contact pressures. Even without subluxation, the
COR+PMCL-elbow showed higher contact pressures compared with the INTACT-elbow.
Treatment of PMRI should be directed toward prevention of joint incongruity,
whether by surgical or nonsurgical means, to prevent high articular contact
pressures.
PMID- 28689822
TI - Fracture line morphology of complex proximal humeral fractures.
AB - BACKGROUND: The aim of this study was to assess proximal humeral fracture
patterns using 3-dimensional computed tomography images and relate them to the
normal osseous landmarks and soft-tissue attachments. METHODS: Forty-eight 3
dimensional computed tomography scans of proximal humeral fractures were
retrospectively collected, and the fractures were transcribed onto proximal
humeral templates. We analyzed the common location and orientation of the
fracture lines, with a focus on fractures of the articular surface, tuberosities,
metaphysis, and proximal diaphysis. These fractures were compared with the
attachments of the rotator cuff and glenohumeral capsule. RESULTS: Fifty-two
percent of the fractures involved the articular surface. No fractures passed
through the bicipital groove, and fractures were more commonly found on the
posterior lesser tuberosity and on the anterior greater tuberosity, coinciding
with the intervals between the rotator cuff tendon insertions. Intracapsular
fractures of the calcar were more common (68%) than extracapsular fractures
(32%). On the anterolateral aspect of the proximal humerus, fractures radiated
from the articular margin, vertically down through the tuberosity zone between
the rotator cuff footprints, meeting horizontally oriented fractures in the
metaphyseal zone. On the posterior aspect, vertical fractures from the tuberosity
zone continued downward to the metaphyseal zone adjacent to the infraspinatus and
teres minor footprints. CONCLUSIONS: Fractures of the proximal humerus follow
characteristic patterns. Fractures frequently split the greater tuberosity and
are closely related to the intervals of the rotator cuff attachments.
PMID- 28689823
TI - Performance and return to sport in elite baseball players and recreational
athletes following repair of the latissimus dorsi and teres major.
AB - BACKGROUND: Tears of the latissimus dorsi (LD) and teres major (TM) are rare but
disabling injuries in the overhead athlete. METHODS: All patients who underwent
an LD and/or TM repair between January 1, 2010, and June 6, 2016, with more than
12 months' follow-up were included. Demographic information and postoperative
range of motion were recorded. Patients were contacted via phone and answered
questions to provide the following: Kerlan-Jobe Orthopaedic Clinic (KJOC)
shoulder and elbow outcome score, American Shoulder and Elbow Surgeons (ASES)
shoulder score, and visual analog scale (VAS) score. Performance data for
professional athletes were recorded preoperatively and postoperatively and
compared by paired t tests. RESULTS: Eleven male patients aged 29.9 +/- 12.4
years were included; 86% were right hand dominant, 86% underwent surgery on the
dominant side, and 73% were pitchers (7 professional and 1 collegiate). The mean
time from injury to repair was 389 +/- 789 days; 36% of repairs were performed
within 6 weeks of injury. At final follow-up, the VAS score was 0.7 +/- 1.9, the
ASES score was 100 +/- 0, and the KJOC score was 93 +/- 5. Professional (major
and minor league) pitchers had a mean total time participating in professional
baseball of 6.6 +/- 3.9 years, with 3.9 +/- 2.3 years before surgery and 2.7 +/-
1.8 years after surgery. Among professional pitchers, the VAS pain score was 0.0
+/- 0.0, the ASES score was 100 +/- 0, and the KJOC score was 89 +/- 2. All
professional pitchers returned to the same level of play. No significant
differences existed between any preoperative and postoperative performance
metrics for pitchers (P > .05). CONCLUSION: Repair of LD and TM tears in both
professional and recreational athletes produces reliable functional recovery with
minimal pain and the ability to return to preoperative athletic activity, even
among elite throwing athletes.
PMID- 28689824
TI - Extra-articular shoulder resections: outcomes of 54 patients.
AB - BACKGROUND: The survival of patients with tumors around the shoulder treated with
extra-articular resection, the rates of reconstructions-related complications,
and the function of the shoulder cannot be estimated because of limited available
data from mainly small published related series and case reports. METHODS: We
studied 54 patients with tumors around the shoulder treated with extra-articular
shoulder resections and proximal humeral megaprosthetic reconstructions from 1985
to 2012. Mean tumor volume was 549 cm3, and the mean length of the proximal
humeral resection was 110 mm. Mean follow-up was 7.8 years (range, 3-21 years).
We evaluated the outcomes (survival, metastases, recurrences, and function) and
the survival and complications of the reconstruction. RESULTS: Survival of
patients with malignant tumors was 47%, 38%, and 35%, at 5, 10, and 20 years,
respectively. Rates for metastasis and local recurrence were 60% and 18.5%,
respectively. Survival was significantly higher for patients without metastases
at diagnosis, tumor volume <549 cm3, and type IV resections. Survival of
reconstructions was 56% at 10 years and 48% 20 years. Overall, 19 patients
(35.2%) experienced 30 complications (55.5%), the most common being soft tissue
failures that required subsequent surgery without, however, implant removal. The
mean Musculoskeletal Tumour Society score was 25 points, without any significant
difference between the types of extra-articular resections. CONCLUSION: Tumor
stage and volume as well as type of resection are important predictors of
survival of patients with malignant tumors around the shoulder. Survival of the
reconstructions is satisfactory; nevertheless, the complication rate is high. The
Musculoskeletal Tumour Society score is similar with respect to the type of
resection.
PMID- 28689825
TI - Biomechanical analysis of anterior bone graft augmentation with reversed shoulder
arthroplasty in large combined glenoid defects compared with total bony joint
line reconstruction (modified bony-increased-offset reversed shoulder
arthroplasty).
AB - BACKGROUND: The aim of this biomechanical study was to compare 2 surgical
techniques for the reconstruction of large, combined, uncontained glenoid defects
with reversed shoulder arthroplasty (RSA). METHODS: Three groups of scapulae with
RSA were tested by the application of a physiological combination of
compressive/shear loads in Sawbones (Pacific Research Laboratories, Inc., Vashon
Island, WA, USA) and cadavers. Two of the groups (both Sawbones and cadaveric
specimens) consisted of anterior combined defects (14 mm in depth), and the third
group served as a control group (only Sawbones specimens). The first group with
an anterior combined defect was reconstructed with anterior bone grafts to
contain the defect and cancellous bone to fill the central defect before RSA with
partial bony joint line reconstruction (p-BJR). In the second group with an
anterior combined defect, the dorsal rim was reamed and the joint line was
reconstructed with a bone disc fully covering the peg. This total BJR (t-BJR)
corresponds to the technique of bony-increased-offset-RSA (BIO-RSA). RESULTS: At
150 um of displacement, the loadings in the inferior-superior (IS) direction were
significantly more stable than those in the anterior-to-posterior (AP) direction
within both reconstructed defect groups (P <= .002). In contrast, no significant
differences were found between the partial BJR and t-BJR group in either
direction (Sawbones: AP: P = .29; IS: P = .44; cadavers: AP: P = .67; IS: P =
.99). The control group revealed significantly higher values in all loadings of
the IS direction and significantly higher loadings at 40 um and 150 um in the AP
direction. CONCLUSION: Both techniques could be applied for such complex defects
provided that there is sufficient medial bone stock for a t-BJR. Significantly
greater stability was found in the IS direction than in the AP direction within
each group, which could be explained by the longer screw anchoring within the
superior and inferior columns. Both defect groups were less stable than the group
of intact glenoids.
PMID- 28689826
TI - Patient self-assessed shoulder comfort and function and active motion are not
closely related to surgically documented rotator cuff tear integrity.
AB - BACKGROUND: The rationale for rotator cuff repair surgery is that better
integrity of the cuff should be associated with better comfort and function.
However, in patients with cuff disease, there is not good evidence that the
degree of rotator cuff integrity is closely associated with the shoulder's
comfort, function, or active motion. The goal of this study was to explore these
relationships in shoulders with surgically documented cuff disease. METHODS: In
55 shoulders having surgery for cuff-related symptoms, we correlated the
preoperative Simple Shoulder Test score with the objectively measured
preoperative active shoulder motion and with the integrity of the cuff observed
at surgery. RESULTS: The 16 shoulders with tendinosis or partial-thickness tears
had an average Simple Shoulder Test score of 3.7 +/- 3.3, active abduction of 111
degrees +/- 38 degrees , and active flexion of 115 degrees +/- 36 degrees . The
corresponding values were 3.6 +/- 2.8, 94 degrees +/- 47 degrees , and 94
degrees +/- 52 degrees for the 22 full-thickness supraspinatus tears and 3.9 +/
2.7, 89 degrees +/- 39 degrees , and 100 degrees +/- 39 degrees for the 17
supraspinatus and infraspinatus tears. CONCLUSION: In this study, surgically
observed cuff integrity was not strongly associated with the shoulder's comfort
or function. Whereas surgeons often seek to improve the integrity of the rotator
cuff, the management of patients with rotator cuff disorders needs to be informed
by a better understanding of the factors other than cuff integrity that influence
the comfort and functioning of shoulders with cuff disease.
PMID- 28689827
TI - Subacromial corticosteroid injections transiently decrease suture anchor pullout
strength: biomechanical studies in rats.
AB - BACKGROUND: Arthroscopic rotator cuff (RC) repair incorporates suture anchors to
secure torn RC tendons to the greater tuberosity (GT) bone. RC repair strength
depends on the anchor-bone interface and on the quality of the GT. We evaluated
the effect of single and multiple corticosteroid injections on the pullout
strength of suture anchors. METHODS: Fifty rats were divided into those receiving
saline solution injection (control group), a single methylprednisolone acetate
(MTA) injection (MTA1 group), or 3 once-weekly MTA injections (MTA3 group). Rats
were killed humanely at 1 or 4 weeks after the last injection. A mini-suture
anchor was inserted into the humeral head through the GT. Specimens were tested
biomechanically. RESULTS: At 1 week after the last injection, the mean maximal
pullout strength was significantly reduced in the MTA1 group (63.5%) and MTA3
group (56%) compared with the control group (P < .05 for both). Mean stiffness
decreased significantly in both treatment groups compared with controls (P <
.05). At 4 weeks after the last injection, there was a significant increase in
the mean maximal pullout strength after single and triple MTA injections compared
with values recorded at the 1-week time point (P < .05). At 4 weeks, the mean
maximal pullout strength after a single MTA injection was 92.8% of the pullout
strength measured in the control group. CONCLUSIONS: We showed a significant
detrimental effect of corticosteroid exposure on the pullout strength of a suture
anchor at 1 week. However, this effect was transient and resolved within a
relatively short period. These findings indicate that a waiting period is
required between subacromial corticosteroid injection and RC repair surgery that
involves the use of suture anchors.
PMID- 28689828
TI - Influence of humeral head material on wear performance in anatomic shoulder joint
arthroplasty.
AB - BACKGROUND: The number of total shoulder arthroplasties has increased in the past
years, with encouraging results. However, the survival of anatomic total shoulder
arthroplasty (aTSA) is lower compared with that of knee and hip replacements.
Wear-associated problems like loosening are well-known causes of long-term
failure of aTSA. The main purpose of this study was to investigate the wear
behavior of ceramic-polyethylene bearings compared with the standard metal
polyethylene bearings. Because there is a lack of valid experimental wear testing
methods, the secondary aim was to develop a validated wear simulation. METHODS:
The wear assessment was performed using a force-controlled joint simulator for 3
* 106 cycles, and polyethylene wear was assessed gravimetrically and by particle
analysis. Kinetic and kinematic data were adopted from in vivo loading
measurements and from several clinical studies on shoulder joint kinematics. The
reaction of the rotator cuff was simulated on the basis of a virtual soft tissue
model. As activity, an abduction-adduction motion of 0 degrees -90 degrees
lifting a load of 2 kg superimposed by an anteversion-retroversion has been
chosen. RESULTS: The studied aTSA resulted in a polyethylene wear rate of 62.75
+/- 1.60 mg/106 cycles in combination with metallic heads. The ceramic heads
significantly reduced the wear rate by 26.7% to 45.99 +/- 1.31 mg/106. There were
no relevant differences in terms of the particle characteristics. CONCLUSION:
This is the first study that experimentally studied the wear behavior of aTSA
based on patient-related and biomechanical data under load-controlled conditions.
Regarding polyethylene wear, the analyzed aTSA could benefit from ceramic humeral
heads.
PMID- 28689829
TI - Polyethylene dissociation from humeral stem status after reverse total shoulder
arthroplasty.
AB - BACKGROUND: Reverse shoulder arthroplasty (RSA) is an important treatment option
for 4-part proximal humerus fractures in the elderly and arthrosis of the
glenohumeral joint with incompetence of the rotator cuff. Unique complications do
occur with use of this type of prosthesis. METHODS: We present 4 cases of
polyethylene dissociation after RSA. RESULTS: In a series of 549 patients who
underwent RSA, the incidence of polyethylene dissociation was found to be 0.7%.
CONCLUSIONS: Polyethylene dissociation is a rare complication after RSA. Surgeons
should be aware of this possibility if a closed reduction of an RSA dislocation
is not possible.
PMID- 28689830
TI - Is bipolar latissimus dorsi transfer a reliable option to restore elbow flexion
in children with arthrogryposis? A review of 13 tendon transfers.
AB - BACKGROUND: Scant data are published about different available therapeutic
options for restoration of active elbow flexion in arthrogryposis with varying
degrees of improvement. In this retrospective study we evaluated medium-term
effects of bipolar latissimus dorsi transfer in patients with arthrogryposis.
METHODS: Pedicled latissimus dorsi bipolar muscle transfer was used to restore
elbow flexion in 11 patients (13 limbs) with arthrogryposis. Elbow and shoulder
range of motions and strength of elbow flexion were measured preoperatively and
at the last follow-up. The functional use of the upper limb was examined by
observation of activities of daily living and presence of adaptive mechanisms.
General satisfaction was assessed at the final follow-up. RESULTS: The patients
were a mean age of 5.69 +/- 2.49 years. The follow-up period was 27.31 +/- 17.8
months. At the last examination, according to transferred muscle function and
elbow range of motion, function of 12 limbs was graded as excellent and good, and
1 was graded poor. The active postoperative elbow range of motion was 97.7
degrees +/- 34.5 degrees . The general satisfaction of the patients with the
surgical results was 92.3%. Activities of daily living were improved in 10 of 13
limbs, but adaptive mechanisms were detected in all patients except 2 at the last
follow-up. CONCLUSIONS: We suggest pedicled bipolar latissimus dorsi transfer as
a reliable therapeutic option to restore active elbow flexion in arthrogryposis
with acceptable results regarding regaining range of motion and patient
satisfaction. Functional passive elbow range of motion and good quality of
latissimus dorsi muscle preoperatively is mandatory.
PMID- 28689831
TI - Successful desensitization of elosulfase alfa-induced anaphylaxis in a pediatric
patient with Morquio syndrome.
PMID- 28689832
TI - Group Allergen Immunotherapy Education Improves Patient Knowledge and Staff
Satisfaction.
PMID- 28689833
TI - Impact of Spacers on Therapeutic Ratio with Inhaled Corticosteroids.
PMID- 28689834
TI - Reply.
PMID- 28689835
TI - Reducing the burden of allergy and asthma in schoolchildren: Air cleaning
solutions and microbial diversity-the dark side of the moon?
PMID- 28689836
TI - Reply.
PMID- 28689837
TI - Correction.
PMID- 28689839
TI - Severe Asthma in Children.
AB - Severe asthma in children is associated with significant morbidity and is a
highly heterogeneous disorder with multiple clinical phenotypes. Cluster analyses
have been performed in several groups to explain some of the heterogeneity of
pediatric severe asthma, which is reviewed in this article. The evaluation of a
child with severe asthma includes a detailed diagnostic assessment and excluding
other possible diagnoses and addressing poor control due to comorbidities, lack
of adherence to asthma controller medications, poor technique, and other
psychological and environmental factors. Children with severe asthma require
significant resources including regular follow-up appointments with asthma
education, written asthma action plan, and care by a multidisciplinary team.
Management of pediatric severe asthma now includes emerging phenotypic-directed
therapies; however, continued research is still needed to further study the long
term outcomes of pediatric severe asthma and its treatment.
PMID- 28689838
TI - Management of Severe Asthma before Referral to the Severe Asthma Specialist.
AB - Severe asthma is associated with significant morbidity and can be challenging to
assess and control, due to heterogeneity of disease, complexity of diagnosis, and
impact of comorbidities. A structured approach to the assessment and management
of severe asthma may be helpful to the practicing clinician. First, it is
important to confirm a diagnosis of asthma. In patients who are either not
responding to treatment, or who require high doses of medication to control
symptoms, it is highly possible that disease mimickers or comorbidities are
present and can inhibit therapeutic responsiveness. The assessment and management
of common comorbidities of asthma may dramatically impact disease control and
thus medication requirement. Determining medication adherence and optimizing drug
dose and delivery may separate out truly severe asthmatics from those not using
medications regularly or properly. Next, although true personalized medicine for
severe asthma is not yet realized, for those individuals with severe asthma,
phenotypic characteristics of each patient may guide which therapeutic options
may be most effective for that patient. Finally, evaluation and management of
severe asthma at a referral center can add additional phenotyping, therapeutic,
and diagnostic strategies.
PMID- 28689840
TI - Severe Asthma Phenotypes - How Should They Guide Evaluation and Treatment?
AB - Although patients with "severe" asthma tend to be characterized by ongoing
symptoms and airway inflammation despite treatment with high doses of inhaled and
systemic corticosteroids, there is increasing recognition of marked phenotypic
heterogeneity within affected patients. Although "precision medicine" approaches
for patients with severe asthma are needed, there are many hurdles that must be
overcome in daily practice. The National Heart, Lung and Blood Institute's Severe
Asthma Research Program (SARP) has been at the forefront of phenotype discovery
in severe asthma for the past decade. SARP, along with other international
groups, has described clinical severe asthma phenotypes in both adults and
children that can be evaluated in the clinical setting. Although these clinical
phenotypes provide a good "starting point" for addressing disease heterogeneity
in severe asthma in everyday practice, more efforts are needed to understand how
these phenotypes relate to underlying disease mechanisms and pharmacological
treatment responses. This review highlights the clinical asthma phenotypes
identified to date, their associations with underlying endotypes and potential
biomarkers, and remaining knowledge gaps that must be addressed before precision
medicine can become a reality for patients with severe asthma.
PMID- 28689841
TI - Biologic Therapy and Novel Molecular Targets of Severe Asthma.
AB - Treatment options for severe or uncontrolled asthma are increasing, especially
pertaining to novel biologic therapies. The 2 primary asthma endotypes, T2 high
and T2 low, are defined by the level of type 2 T helper and innate lymphoid cell
activity and mediators. Most therapies for severe asthma target T2 high asthma,
including the 3 biologics approved for use in the United States and Europe:
omalizumb, mepolizumb, and reslizumab. Other biologics, with various molecular
targets, are under investigation. Unfortunately, treatment options for T2 low
asthma are limited. Although these therapies may improve asthma symptoms,
exacerbation rates, and lung function parameters, they have not been shown to
modify the disease process or provide lasting benefits after discontinuation.
Biomarkers identified thus far to help guide individualized therapy in severe
asthma are helpful, but imperfect discriminators for picking the best option for
individual patients. This review will discuss the mechanisms of action,
indications, and therapeutic effects of currently available and emerging
biologics for the treatment of severe or uncontrolled asthma.
PMID- 28689842
TI - Asthma Exacerbations: Pathogenesis, Prevention, and Treatment.
AB - Guideline-based management of asthma focuses on disease severity and choosing the
appropriate medical therapy to control symptoms and reduce the risk of
exacerbations. However, irrespective of asthma severity and often despite optimal
medical therapy, patients may experience acute exacerbations of symptoms and a
loss of disease control. Asthma exacerbations are most commonly triggered by
viral respiratory infections, particularly with human rhinovirus. Given the
importance of these events to asthma morbidity and health care costs, we will
review common inciting factors for asthma exacerbations and approaches to prevent
and treat these events.
PMID- 28689843
TI - Nonpharmacologic Therapy for Severe Persistent Asthma.
AB - The treatment of asthma largely depends on guideline-based pharmacologic
therapies. However, nonpharmacologic therapies for asthma such as pulmonary
rehabilitation, focused breathing techniques, and bronchial thermoplasty have an
important, yet underappreciated, role. Structured pulmonary rehabilitation
programs can reduce dyspnea and increase cardiopulmonary fitness. The educational
component of these programs can ensure that therapies are being used
appropriately, increase compliance, and decrease health care utilization. Studies
have demonstrated a reduction in inflammatory mediators in patients with asthma
who are engaged in an exercise program. Focused breathing techniques are commonly
used by patients with asthma, yet benefit has not been clearly shown in
randomized controlled trials. For the patients with severe asthma who are
unresponsive to maximum medical therapy and have evidence of airway remodeling,
bronchial thermoplasty has demonstrated long-term improvement in quality of life
and reduction in severe exacerbations and health care utilization. Recent airway
biopsy studies have demonstrated bronchial thermoplasty's disease-modifying
effect on smooth muscle, inflammatory mediators, and bronchial nerve endings.
These nonpharmacologic therapies are complementary to current guideline-based
treatment, including the use of biologic modifiers, for severe asthma.
PMID- 28689844
TI - The Many "Buckets" of Severe Asthma: Moving Toward Personalized Management.
PMID- 28689845
TI - A Systematic Approach to Evaluating Difficult to Control Asthma: A Little Goes a
Long Way.
PMID- 28689846
TI - Up in Smoke: Accelerated Loss of Lung Function in Two Clusters of Smokers
Identified in a Longitudinal Cohort Study of Adult-Onset Asthma.
PMID- 28689847
TI - More Reason to Watch Your Weight During Pregnancy.
PMID- 28689848
TI - From the Editor: Using PCSK9 inhibitors in practice.
PMID- 28689849
TI - Screening for microplastics in sediment, water, marine invertebrates and fish:
Method development and microplastic accumulation.
AB - Measurements of microplastics in biota and abiotic matrices are key elements of
exposure and risk assessments for this emerging environmental pollutant. We
investigated the abundance of microplastics in field-collected biota, sediment
and water. An improved sediment extraction method, based on density separation
was developed. For analysis of microplastics in biota we found that an adapted
enzymatic digestion protocol using proteinase K performed best, with a 97%
recovery of spiked plastic particles and no observed degradation effects on the
plastics in subsequent Raman analysis. Field analysis revealed that 8 of 9 tested
invertebrate species from the North Sea and 68% of analyzed individuals of brown
trout (Salmo trutta) from the Swedish West Coast had microplastics in them. Based
on the number of plastic particles per kg d.w. the microplastic concentrations
found in mussels were approximately a thousand-fold higher compared to those in
sediment and surface water samples from the same location.
PMID- 28689850
TI - miR-215 promotes cell migration and invasion of gastric cancer by targeting
Retinoblastoma tumor suppressor gene 1.
AB - BACKGROUND: Gastric cancer (GC) is one of the most common malignant tumor and has
high mortality worldwide. microRNAs (miRNAs) play critical roles in
carcinogenesis. Previous studied showed that miR-215 was involved in
tumorigenesis and progression. This study was designed to clarify the biological
function of miR-215 in GC. METHODS: qRT-PCR was used to detect the miR-215
expression in GC tissues and 6 human GC cell lines (AGS, SGC-7901, NCI-N87, GES
1, MKN-45 and BGC-823) as well. Transwell assay was used to investigate the
biological function of miR-215 in GC. Luciferase reporter assay was used to
confirm its effect on the regulation of the target gene Retinoblastoma tumor
suppressor gene 1 (RB1). RESULTS: miR-215 was frequently up-regulated in GC
tissues compared to adjacent non-tumor tissues and GC cell lines. miR-215
expression level was correlated with the progression of tumor invasion and tumor
node-metastasis (TNM) stage. Over-expression miR-215 in GC cell lines promoted
cell migration and invasion. Besides, miR-215 could down-regulate the expression
of RB1 in vitro via directly binding to its 3'-untranslated region (UTR), while
the expression of RB1 would suppress the miR-215-indueced GC cell migration and
invasion. CONCLUSIONS: miR-215 promoted cell migration and invasion of gastric
cancer by directly targeting RB1.
PMID- 28689851
TI - Corrigendum to 'Liver receptor Homolog-1 regulates mouse superoxide dismutase 2'
[Biochem. Biophys. Res. Comm. 489(3) (2017) 299-304].
PMID- 28689852
TI - Development of an integrated cognitive behavioral therapy for anxiety and opioid
use disorder: Study protocol and methods.
AB - Opioid use disorder is a highly disabling psychiatric disorder, and is associated
with both significant functional disruption and risk for negative health outcomes
such as infectious disease and fatal overdose. Even among those who receive
evidence-based pharmacotherapy for opioid use disorder, many drop out of
treatment or relapse, highlighting the importance of novel treatment strategies
for this population. Over 60% of those with opioid use disorder also meet
diagnostic criteria for an anxiety disorder; however, efficacious treatments for
this common co-occurrence have not be established. This manuscript describes the
rationale and methods for a behavioral treatment development study designed to
develop and test an integrated cognitive-behavioral therapy for those with co
occurring opioid use disorder and anxiety disorders. The aims of the study are
(1) to develop and pilot test a new manualized cognitive behavioral therapy for
co-occurring opioid use disorder and anxiety disorders, (2) to test the efficacy
of this treatment relative to an active comparison treatment that targets opioid
use disorder alone, and (3) to investigate the role of stress reactivity in both
prognosis and recovery from opioid use disorder and anxiety disorders. Our
overarching aim is to investigate whether this new treatment improves both
anxiety and opioid use disorder outcomes relative to standard treatment.
Identifying optimal treatment strategies for this population are needed to
improve outcomes among those with this highly disabling and life-threatening
disorder.
PMID- 28689853
TI - Identification of patients with primary ovarian insufficiency caused by
autoimmunity.
AB - Autoimmune pathogenesis is responsible for a subset of primary ovarian
insufficiency (POI) cases. The significance of autoantibodies for POI, however,
remains unclear. A total of 250 women with idiopathic POI and 256 age-matched
healthy women were enrolled. The presence in serum of adrenal cortex autoantibody
(AAA), detected by indirect immunofluorescence and non-organ-specific antibodies,
including antinuclear antibody, anti-cardiolipin antibody, and anti-double
stranded DNA antibody, detected by enzyme-linked immunosorbent assay, was
compared. Ovarian biopsy was carried out for histology assessment. Adrenal
function was followed-up in 15 women with POI who were positive for AAA. Higher
frequency of positive AAA was observed in women with POI (19.2%) compared with
controls (5.9%, P < 0.01). No difference in anti-cardiolipin antibody,
antinuclear antibody and anti-double stranded DNA antibody was found between the
two groups. Ovarian biopsies in 13 women with POI (six AAA positive and seven
negative) showed atrophic ovaries devoid of follicles. One out of fifteen women
positive for AAA had symptoms of adrenal insufficiency 3 years after POI
diagnosis. Significantly higher positive frequency of AAA in POI patients
suggests the role of autoimmune disturbance in pathogenesis. Therefore, AAA may
serve as a biomarker for ovarian autoimmunity.
PMID- 28689854
TI - Impact of cardiac rehabilitation and exercise training programs in coronary heart
disease.
AB - Cardiovascular rehabilitation (CR) is the process of developing and maintaining
an optimal level of physical, social, and psychological well-being in order to
promote recovery from cardiovascular (CV) illness. It is a multi-disciplinary
approach encompassing supervised exercise training, patient counseling, education
and nutritional guidance that may also enhance quality of life. Beneficial CV
effects may include improving coronary heart disease risk factors; particularly
exercise capacity, reversing cardiac remodeling, and favorably modifying
metabolism and systemic oxygen transport. We review the historical basis for
contemporary CR, the indications and critical components of CR, as well as the
potential salutary physiological and clinical effects of exercise-based CR.
PMID- 28689855
TI - PlanYourLifeSpan.org - an intervention to help seniors make choices for their
fourth quarter of life: Results from the randomized clinical trial.
AB - OBJECTIVE: Few older adults contemplate their home support and health needs that
may be required for aging-in-place. We sought to assess the efficacy of
PlanYourLifespan.org (PYL), in influencing seniors' planning behaviors,
perception of the importance of planning, and confidence accessing services.
METHOD: Randomized controlled trial, of adults, age >=65 years in urban,
suburban, rural areas of Texas, Illinois, Indiana. RESULTS: Among 385
participants, mean age was 71.9 years, 79.5% female. Between baseline and one
month follow-up, average planning behavior score increased 0.22 points in the PYL
arm when compared to the attention control (AC) arm. After controlling for
baseline, mean one-month planning behavior score was significantly higher in the
PYL arm than in the AC arm (1.25 points, CI 0.37-2.12, p=0.005). Secondary
analyses via longitudinal linear mixed modelling suggested a study arm-by-time
interaction effect for both planning behavior (p=0.047 and perception of
importance (p=0.05). Significant baseline covariates included self-efficacy,
education, perceived social support, power of attorney, and history of stroke.
CONCLUSIONS AND PRACTICE IMPLICATIONS: PlanYourLifespan.org demonstrated efficacy
in helping seniors plan for and communicate their health support needs. This
free, nationally available tool may help individuals understand, plan, and
communicate their options for their future support needs.
PMID- 28689856
TI - Restrictions on access to direct-acting antivirals for people who inject drugs:
The European Hep-CORE study and the role of patient groups in monitoring national
HCV responses.
PMID- 28689857
TI - Risk of misclassification with a non-fasting lipid profile in secondary
cardiovascular prevention.
AB - AIMS: Routinely fasting is not necessary for measuring the lipid profile
according to the latest European consensus. However, LDL-C tends to be lower in
the non-fasting state with risk of misclassification. The extent of
misclassification in secondary cardiovascular prevention with a non-fasting lipid
profile was investigated. METHODS AND RESULTS: 329 patients on lipid lowering
therapy for secondary cardiovascular prevention measured a fasting and non
fasting lipid profile. Cut-off values for LDL-C, non-HDL-C and apolipoprotein B
were set at <1.8mmol/l, <2.6mmol/l and <0.8g/l, respectively. Study outcomes were
net misclassification with non-fasting LDL-C (calculated using the Friedewald
formula), direct LDL-C, non-HDL-C and apolipoprotein B. Net misclassification
<10% was considered clinically irrelevant. Mean age was 68.3+/-8.5years and the
majority were men (79%). Non-fasting measurements resulted in lower LDL-C (-0.2+/
0.4mmol/l, P<0.001), direct LDL-C (-0.1+/-0.2mmol/l, P=0.001), non-HDL-C (-0.1+/
0.4mmol/l, P=0.004) and apolipoprotein B (-0.02+/-0.10g/l, P=0.004). 36.0% of the
patients reached a fasting LDL-C target of <1.8mmol/l with a significant net
misclassification of 10.7% (95% CI 6.4-15.0%) in the non-fasting state. In the
non-fasting state net misclassification with direct LDL-C was 5.7% (95% CI 2.1
9.2%), 4.0% (95% CI 1.0-7.4%) with non-HDL-C and 4.1% (95% CI 1.1-9.1%) with
apolipoprotein B. CONCLUSION: Use of non-fasting LDL-C as treatment target in
secondary cardiovascular prevention resulted in significant misclassification
with subsequent risk of undertreatment, whereas non-fasting direct LDL-C, non-HDL
C and apolipoprotein B are reliable parameters.
PMID- 28689858
TI - Singapore grouper iridovirus (SGIV) TNFR homolog VP51 functions as a virulence
factor via modulating host inflammation response.
AB - Virus encoded tumor necrosis factor receptor (TNFR) homologues are usually
involved in immune evasion by regulating host immune response or cell death.
Singapore grouper iridovirus (SGIV) is a novel ranavirus which causes great
economic losses in aquaculture industry. Previous studies demonstrated that SGIV
VP51, a TNFR-like protein regulated apoptotic process in VP51 overexpression
cells. Here, we developed a VP51-deleted recombinant virus Delta51-SGIV by
replacing VP51 with puroR-GFP. Deletion of VP51 resulted in the decrease of SGIV
virulence, evidenced by the reduced replication in vitro and the decreased
cumulative mortalities in Delta51-SGIV challenged grouper compared to WT-SGIV.
Moreover, VP51 deletion significantly increased virus induced apoptosis, and
reduced the expression of pro-inflammatory cytokines in vitro. In addition, the
expression of several pro-inflammatory genes were decreased in Delta51-SGIV
infected grouper compared to WT-SGIV. Thus, we speculate that SGIV VP51 functions
as a critical virulence factor via regulating host cell apoptosis and
inflammation response.
PMID- 28689859
TI - Pancreatitis with normal lipase and amylase in setting of end-stage renal
disease.
AB - Pancreatitis with normal lipase and amylase level is a rare phenomenon. This is
especially true in patient with end-stage renal disease as lipase and amylase are
renally excreted. Literature review reveals previous case report of pancreatitis
with normal lipase and amylase level, however, none of them occurred in the
setting of end-stage renal disease. Our case is the first such reported case of
pancreatitis in such setting. Here we report a 30year old male with past medical
history of end-stage renal disease who presented in emergency department with
acute abdominal pain. Laboratory work up revealed normal lipase and amylase
level. However, radiological work up was consistent with pancreatitis. This case
report highlight the importance of taking the overall clinical picture rather
than laboratory work up to rule in or rule out the diagnosis of pancreatitis.
Furthermore, this should also serve an important reminder for clinicians to
further investigate where clinical suspicion for pancreatitis is high.
PMID- 28689860
TI - The expression pattern of hsp70 plays a critical role in thermal tolerance of
marine demersal fish: Multilevel responses of Paralichthys olivaceus and its
hybrids (P. olivaceus ? * P. dentatus ?) to chronic and acute heat stress.
AB - Ocean warming has multifaceted impacts on marine organisms. This study
investigated the different responses of Paralichthys olivaceus and the hybrids
(P. olivaceus ? * P. dentatus ?) to chronic and acute heat stress. By comparing
their survival, behavioural and histological changes, we found that the hybrids
possess a better thermal tolerance with a higher cumulative survival rate (CSR),
relatively fewer behavioural changes and less gill damage. Moreover, we analysed
the relationship between thermal tolerance and the hsp70 expression pattern and
found that thermal tolerant species (the hybrids) exhibited higher threshold
induction temperature, shorter durations, stronger magnitudes and a delay in
hsp70 expression. We speculated that the expression mode of hsp70, rather than
itself, plays a critical role in thermal tolerance. These findings would improve
the understanding of hsp70 in future marine climate research and help clarify the
profound effects of rising temperature on marine demersal fishes.
PMID- 28689861
TI - The relationship between physical activity and post-operative length of hospital
stay: A systematic review.
AB - BACKGROUND: Recovery from surgery has traditionally been measured using specific
outcome measures, such as length of hospital stay. However, advances in
technology have enabled the measurement of continuous, objective physical
activity data in the perioperative period. The aim of this systematic review was
to determine the relationship between length of hospital stay and physical
activity data for patients undergoing surgery. METHODS: A systematic search of
EMBASE, Medline and the Cochrane Library, from inception until January 2017, was
performed to identify all study designs that evaluated physical activity after
surgery. Studies were included if a wearable sensor measured patient activity as
an in-patient and the length of hospital stay was reported. Only English articles
were included. RESULTS: Six studies with a total of 343 participants were
included in this review. All the studies were prospective observational studies.
Each study used a different sensor, with the commonest being a tri-axial
accelerometer, and multiple different physical activity outcome measures were
used, thereby prohibiting meta-analysis. Four of the studies demonstrated a
relationship between physical activity levels and length of hospital stay, while
two studies did not show any significant relationship. CONCLUSION: The amount of
physical activity performed post-operatively negatively correlates with the
length of hospital stay. This suggests that objective physical activity data
collected by body worn sensors may be capable of predicting functional recovery
post-operatively.
PMID- 28689862
TI - Histological fibrosis may predict the failure of core decompression in the
treatment of osteonecrosis of the femoral head.
AB - PURPOSE: Osteonecrosis of femoral head (ONFH) is histopathologically
characterized by necrotic areas associated with reactive fibrosis, trabecular
bone remodeling and thickening zones. Our double goal was to evaluate if: 1) main
ONFH risk factors were related to specific histological specimen patterns 2)
different histological patterns were related to the final outcome after a core
decompression (CD) procedure. METHODS: This observational longitudinal cohort
study respected the STROBE statement. We described a series of 41 ONFH (Ficat
stage I and II) treated by CD. Specimens from core biopsies were scored according
to the extension of necrosis, fibrosis, trabecular bone remodeling and
thickening, and were correlated (multivariate analysis) to clinical, biological
and radiological factors (age, delay between symptoms onset and surgery, alcohol,
steroids, smoking, related disease, cholesterol, triglycerides, x-ray and MRI
findings). Prospectively, differences in survivorship among different
histological patterns were assessed (log-rank test on Kaplan-Meier curves).
Minimum follow-up was 3 years. RESULTS: Risk factors did not correlate with the
histological pattern. The CD survival rate was progressively decreased at 36
months after surgery, thereafter, remained relatively constant (59% at 1 year,
46% at 2 years, 37% at 3 and 5 years). A survival sub-analysis showed a higher CD
survivorship in patients with lower extension of fibrosis on core biopsies than
patients with high fibrosis levels (log rank p = 0.019). CONCLUSIONS: The
extension of fibrosis on specimens from biopsies in ONFH is a predictor of the
outcome of the CD, therefore it may be considered a prognostic variable. However,
it did not correlate with any risk factor. Different ONFH risk factors background
did not correlate with specific histological patterns.
PMID- 28689863
TI - Long term results of open complex abdominal wall hernia repair with self-gripping
mesh: A retrospective cohort study.
AB - BACKGROUND: In case of complex ventral hernias, Rives-Stoppa and component
separation technique are considered as favourable treatment techniques. However,
mesh-related complications like recurrence, infection and chronic pain are still
a common problem after mesh repair. Previous studies have reported promising
results of the use of a self-gripping mesh (ProGripTM) in incisional hernia
repair. This study aimed to evaluate the long term results of this mesh for
complex ventral hernia treatment. MATERIALS AND METHODS: Patients with complex
ventral hernia undergoing repair between June 2012 and June 2015, using the
ProGripTM-mesh in retromuscular position, were included. All patients visited the
outpatient clinic to evaluate short term complications and recurrence. After at
least one year, telephone interviews were conducted to evaluate long term
results. RESULTS: A total of 46 patients (median age 59 years) were included. 40
patients (87%) were diagnosed with incisional hernia. Seven patients (18%) had
incisional hernia combined with another hernia. Four patients (8.7%) had an
umbilical hernia, one patient (2.2%) had an epigastric hernia and one patient
(2.2%) had rectus diastasis. 39 patients completed follow-up. Median follow-up
was 25 months (IQR: 19-35 months). 28 patients (72%) did not report any
complaints. Nine patients reported pain (average VAS of 1.7). Two patients
developed a recurrence requiring reoperation. One patient developed mesh
infection requiring reoperation. CONCLUSION: Long term results of the use of a
self-gripping mesh for complex abdominal wall hernias show a low recurrence rate,
even in complex hernia cases. This makes the mesh a good choice in this difficult
patient group.
PMID- 28689864
TI - Long-term complications arising from bowel interposition in the urinary tract.
AB - After radical cystectomy or pathologies affecting the ureter(s), bowel segments
can be employed to restore the natural urine flow or to create an external
urinary diversion. Nevertheless, the interposition of bowel segments in the
urinary tract is not devoid of complications. In fact, bowel's microstructure
differs from the urothelium; specifically its mucosa is aimed at reabsorption,
rather than storage. The aim of this paper is to revise the pathophysiology of
complications related to bowel's mucosal properties. Those are: metabolic
imbalance, malabsorption of vitamins, cholelitiasis, nephrolitiasis and
infections. Their entity varies according to the segment used and to its length,
which reflects the surface in contact with urine. Mostly, they occur on the long
term, but metabolic imbalances might occur soon after surgery as well.
PMID- 28689865
TI - Factors associated with recurrence after colpocleisis for pelvic organ prolapse
in elderly women.
AB - INTRODUCTION: The aim of this study was to evaluate the factors associated with
recurrence after colpocleisis for pelvic organ prolapse in elderly women.
METHODS: This was a retrospective cohort study of patients who underwent
colpocleisis for stage 3 or 4 pelvic organ prolapse at a single tertiary center
from January 2007 to December 2015. RESULTS: A total of 107 patients who
underwent colpocleisis were reviewed. Duration from prolapse occurrence to
surgery was significantly longer (24.6 +/- 22.8 years vs 8.0 +/- 12.9 years, p =
0.021) in patients who had recurrence after colpocleisis than in those without
recurrence. CONCLUSION: Duration of prolapse was longer in patients with
recurrence than in those who had a successful outcome.
PMID- 28689866
TI - Pancreatic resection in the era of laparoscopy: State of Art. A systematic
review.
AB - BACKGROUND: Innovation in surgical devices and improvement in laparoscopic skills
have gradually led to achieve more challenging surgical procedures. Among these
demanding interventions is the pancreatic surgery that is seen as
intraoperatively risky and with high postoperative morbi-mortality rate. In order
to understand the complexity of laparoscopic pancreatic surgery, we performed a
systematic review of literature. DATA SOURCE: A systematic review of literature
was performed regarding laparoscopic pancreatic resection. RESULTS: Laparoscopic
approach in pancreas resections has been extensively reported as safe and
feasible regarding pancreaticoduodenectomy, distal pancreatectomy and pancreatic
enucleation. Compared to open approach, no benefit in morbi-mortality has been
demonstrated (except for laparoscopic distal pancreatectomy) and no controlled
randomized trials have been reported. CONCLUSIONS: Laparoscopic approach is not
workable in all patients and patient selection is not standardized. Additionally,
most optimistic reports considering laparoscopic approach are produced by
tertiary centres. Currently, two tasks should be accomplished 1 degrees )
standardization of the laparoscopic pancreatic procedures 2 degrees ) comparative
trials to assess endpoint benefits of laparoscopic pancreatic resection compared
with open procedures.
PMID- 28689867
TI - Ex vivo activity of Proveblue, a methylene blue, against field isolates of
Plasmodium falciparum in Dakar, Senegal from 2013-2015.
AB - Resistance to most antimalarial drugs has spread from Southeast Asia to Africa.
Accordingly, new therapies to use with artemisinin-based combination therapy
(triple ACT) are urgently needed. Proveblue, a methylene blue preparation, was
found to exhibit antimalarial activity against Plasmodium falciparum strains in
vitro. Proveblue has synergistic effects when used in combination with
dihydroartemisinin, and has been shown to significantly reduce or prevent
cerebral malaria in mice. The objectives of the current study were to evaluate
the in vitro baseline susceptibility of clinical field isolates to Proveblue,
compare its activity with that of other standard antimalarial drugs and define
the patterns of cross-susceptibility between Proveblue and conventional
antimalarial drugs. The Proveblue IC50 of 76 P. falciparum isolates ranged from
0.5 nM to 135.1 nM, with a mean of 8.1 nM [95% confidence interval, 6.4-10.3].
Proveblue was found to be more active against P. falciparum parasites than
chloroquine, quinine, monodesethylamodiaquine, mefloquine, piperaquine,
doxycycline (P <0.001) and lumefantrine (P = 0.014). Proveblue was as active as
pyronaridine (P = 0.927), but was less active than dihydroartemisinin and
artesunate (P <0.001). The only significant cross-susceptibilities found were
between Proveblue and dihydroartemisinin (r2 = 0.195, P = 0.0001), artesunate (r2
= 0.187, P = 0.0002) and piperaquine (r2 = 0.063, P = 0.029). The present study
clearly demonstrates the potential of Proveblue as an effective therapeutic agent
against P. falciparum. In this context, the use of Proveblue as part of the
triple ACT treatment for multidrug-resistant malaria warrants further
investigation.
PMID- 28689868
TI - Evaluation of haemodialysis as a protective technique for preventing high daily
dose amikacin nephrotoxicity: an experimental study in an ovine model.
AB - Changes in pharmacokinetic parameters of critically ill patients make the
treatment of infections challenging, particularly when multidrug-resistant
bacteria are involved. The aim of this study was to evaluate the ability of
haemodialysis to reduce the exposure to high dose amikacin and prevent
nephrotoxicity. Amikacin 50 mg/kg was administered intravenously to six adult
sheep once-daily for four days. The sheep were divided into two groups according
to the implementation (group 1) or not (group 2) of haemodialysis. In group 1,
haemodialysis was performed for 4 h, initiated 2 h after starting amikacin
infusion. Amikacin area under the curve (AUC) and trough concentrations (Cmin)
were used as markers of amikacin-induced nephrotoxicity. The median haemodialysis
amikacin clearance was 2.14 L/h (35.6 mL/min), 14% of the mean total body
clearance for 24 h. Haemodialysis reduced Cmin (group 1: 0.3 ug/mL [0.3-1.1];
group 2: 1.4 ug/mL [1.1-3.9]; P = 0.0003). A trend towards reduced AUC with
haemodialysis was observed (group 1: 1450 ug/mL?h [1311-1716]; group 2: 3126
ug/mL?h [2581-3171]; P = 0.10). In conclusion, haemodialysis seems interesting in
reducing AUC and Cmin after the injection of high-dose of amikacin, parameters
known to be involved in its induced nephrotoxicity, in an experimental ovine
model.
PMID- 28689869
TI - Effects of oral antibiotics and isotretinoin on the murine gut microbiota.
AB - Inflammatory bowel disease (IBD) may develop due to an immunogenic response to
commensal gut microbiota triggered by environmental factors in the genetically
susceptible host. Isotretinoin, applied in the treatment of severe acne, has been
variably associated with IBD, but prior treatment with antibiotics, also
associated with IBD development, confounds confirmation of this association. This
study investigated the effects of doxycycline, metronidazole (frequently used in
the treatment of acne and IBD, respectively) and isotretinoin on murine gut
(faecal) microbiota after 2 weeks of treatment and after a 4-week recovery
period. Faecal microbiota composition was assessed by 16S rRNA gene sequencing on
the GS-FLX 454 platform with primers directed against the variable regions V1-V2.
Doxycycline had a modest effect on bacterial richness and evenness, but had
pronounced persistent and significant effects on the abundance of certain
operational taxonomic units compared with the control group. In contrast,
metronidazole induced a pronounced reduction in diversity after treatment, but
these effects did not persist after the recovery period. This study demonstrates
differential effects of antibiotics on the gut microbiota with doxycycline,
unlike metronidazole, mediating long-term changes in the murine gut microbiota.
Isotretinoin had no significant effect on the faecal microbiota.
PMID- 28689870
TI - In vitro and in vivo evaluation of fluoroquinolone resistance associated with DNA
gyrase mutations in Francisella tularensis, including in tularaemia patients with
treatment failure.
AB - Fluoroquinolones (FQs) are highly effective for treating tularaemia, a zoonosis
caused by Francisella tularensis, but failures and relapses remain common in
patients with treatment delay or immunocompromised status. FQ-resistant strains
of F. tularensis harboring mutations in the quinolone-resistance determining
region (QRDR) of gyrA and gyrB, the genes encoding subunits A and B of DNA
gyrase, have been selected in vitro. Such mutants have never been isolated from
humans as this microorganism is difficult to culture. In this study, the presence
of FQ-resistant mutants of F. tularensis was assessed in tularaemia patients
using combined culture- and PCR-based approaches. We analyzed 42 F. tularensis
strains and 82 tissue samples collected from 104 tularaemia cases, including 32
(30.7%) with FQ treatment failure or relapse. Forty F. tularensis strains and 55
clinical samples were obtained before any FQ treatment, while 2 strains and 15
tissue samples were collected after treatment. FQ resistance was evaluated by the
minimum inhibitory concentration (MIC) for the bacterial strains, and by newly
developed PCR-based methods targeting the gyrA and gyrB QRDRs for both the
bacterial strains and the clinical samples. None of the F. tularensis strains
displayed an increased MIC compared with FQ-susceptible controls. Neither gyrA
nor gyrB QRDR mutation was found in bacterial strains and tissue samples tested,
including those from patients with FQ treatment failure or relapse. Further
phenotypic and genetic resistance traits should be explored to explain the poor
clinical response to FQ treatment in such tularaemia patients.
PMID- 28689871
TI - CD101, a long-acting echinocandin, and comparator antifungal agents tested
against a global collection of invasive fungal isolates in the SENTRY 2015
Antifungal Surveillance Program.
AB - CD101 is a novel echinocandin with exceptional chemical stability and long-acting
pharmacokinetics. The activity of CD101 and comparators was evaluated using CLSI
broth microdilution methods against 713 invasive fungal isolates, including 589
Candida spp. (6 species), 14 C. neoformans, 97 A. fumigatus and 13 A. flavus
species complex collected worldwide during 2015. All C. tropicalis, C. krusei and
C. dubliniensis, 99.7% of C. albicans and 98.3% of C. glabrata were inhibited by
<=0.12 ug/mL of CD101, and these isolates were susceptible/wild type to other
echinocandins using CLSI clinical breakpoint and epidemiological cutoff value
(ECV) interpretive criteria. C. parapsilosis displayed higher MIC values (range
0.25-2 ug/mL), but similar results were observed for other echinocandins. One C.
glabrata and one C. albicans with CD101 MIC value at 1 and 0.25 ug/mL possessed
F625S and S645P alterations on FKS1, respectively. These isolates also displayed
elevated MIC values for at least one clinically available echinocandin.
Fluconazole resistance was noted for 6.6% of C. glabrata and 3.6% C.
parapsilosis. Echinocandins had limited activity against C. neoformans. CD101
activity against A. fumigatus and A. flavus (MEC <=0.03 ug/mL) was comparable to
other echinocandins (MEC <=0.03 ug/mL). These moulds had MIC values below ECVs
for the mould-active azoles. CD101 was as active as other echinocandins against
common fungal organisms recovered from invasive fungal infections. The extended
half-life profile is very desirable as less frequent dosing of this agent should
facilitate shorter and more cost-effective hospital stays, improve compliance for
outpatients, and provide more convenient outpatient prophylaxis.
PMID- 28689872
TI - Salvage therapy for complex bone and joint infections with ceftaroline: a
multicentre, observational study.
PMID- 28689873
TI - Chitosans inhibit the growth and the adhesion of Klebsiella pneumoniae and
Escherichia coli clinical isolates on urinary catheters.
AB - OBJECTIVE: The aim of this study was to determine the antimicrobial activity of
different chitosans (CS) against typical colonizing pathogens of the urinary
tract and to assess their efficacy against bacterial adhesion and the subsequent
biofilm formation on urinary catheters. METHODS: The antimicrobial activity of
high and low molecular weight CS (50 and 150 kDa) at pH 5.0 and 6.0 was tested
against Klebsiella pneumoniae and Escherichia coli clinical isolates by time-kill
studies. The anti-adhesion assays on Foley urinary catheters were performed in
Artificial Urine Medium (AUM) with the addition of each CS (AUM-CS) at the same
pH values. Finally, the efficacy over time of chitosan treatments on bacterial
adhesion on urinary catheters was determined. RESULTS: A viability reduction of
K. pneumoniae and E. coli isolates, regardless of pH value, was evidenced in time
kill studies, in particular in the presence of CS 50 kDa. As regards the anti
adhesion efficacy on urinary catheters, high and low molecular weight CS
evidenced a higher efficacy to reduce bacterial adhesion at pH 5.0. A low number
of viable K. pneumoniae and E. coli cells were recovered from catheters after CS
treatments, highlighting a promising efficacy over time. CONCLUSION: Our data
show the potential of chitosans to reduce or prevent not only the adhesion of
well-known human uropathogens on urinary catheters but also the re-growth ability
of the uropathogens.
PMID- 28689874
TI - Shortening the incubation time for the combination disk diffusion extended
spectrum beta-lactamase (ESBL) confirmation test: how far can we go?
AB - The combination disk diffusion extended-spectrum beta-lactamase (ESBL)
confirmation test (CDT) is used for the confirmation of ESBL production in
Enterobacteriaceae and usually takes 16-20 h to results. In this study, we
searched for the shortest possible incubation time without a reduction in
reliability. A total of 125 ESBL screening-positive isolates were subjected to
CDT and were molecularly characterised by microarray. Inhibition zones were read
every hour over 6-18 h of incubation. Concordance between earlier and 18-h
readings was calculated for each hour. Results were validated on 224 isolates
during routine clinical practice. For the initial 125 isolates, concordance
(Cohen's kappa) between the 6-h and 18-h readings was 0.88 [95% confidence
interval (CI) 0.78-0.96; P <0.001]. The earliest time point for full concordance
with the 18-h reading was 10 h. Validation of the 10-h reading for 224 clinical
isolates resulted in a concordance of 0.99 (95% CI 0.98-1.0) between the 10-h and
18-h readings. Overall concordance on all 349 isolates was 0.99 (95% CI 0.97
1.0). Reading after 10 h of incubation has an excellent correlation with results
after 18 h of incubation. This can significantly reduce the turnaround time for
ESBL detection in laboratories with long opening hours or providing a 24/7
service. Consequently, there is a potential for implementing infection control
measures up to 8 h earlier.
PMID- 28689875
TI - Contribution of AcrAB-TolC to multidrug resistance in an Escherichia coli
sequence type 131 isolate.
AB - Drug efflux by resistance-nodulation-cell division (RND)-type transporters, such
as AcrAB-TolC of Escherichia coli, is an important resistance mechanism in Gram
negative bacteria; however, its contribution to multidrug resistance (MDR) in
clinical isolates is poorly defined. We inactivated acrB of a sequence type 131
E. coli human isolate that showed high-level MDR, but had no mutations within the
known efflux-associated local or global regulators. The resistance profile of the
acrB deletion mutant revealed significantly increased susceptibility to drugs
from seven antibiotic classes, including agents usually inactive against Gram
negative bacteria, notably the new oxazolidinone, tedizolid (512-fold enhanced
susceptibility). AcrB deficiency reduced, but did not abolish, the efflux of
dyes, which indicates the activity of at least one more efflux transporter. The
findings demonstrate the efficacy of AcrAB-TolC-mediated broad-spectrum drug
efflux, including agents primarily developed for Gram-positive pathogens, in a
clinical isolate representative of a globally-emerging lineage. The results
illustrate the need to develop molecules modified to impede their transport by
AcrAB-TolC and its homologues and new efflux inhibitors.
PMID- 28689876
TI - Impact of renal replacement modalities on the clearance of piperacillin
tazobactam administered via continuous infusion in critically ill patients.
AB - This prospective pharmacokinetic study aimed to compare the clearance of
piperacillin-tazobactam administered as a 24-h continuous infusion between
continuous venovenous haemodiafiltration (CVVHDF) and continuous venovenous
haemofiltration (CVVH) applied at equal dose in critically ill patients. A
loading dose of 4.5 g of piperacillin-tazobactam followed by a continuous
infusion (500 mg/h) was administered to patients randomized to receive CVVHDF or
CVVH. Serial pre- and postfilter blood samples were drawn during an 8-h sampling
interval. Piperacillin plasma concentrations were measured using a validated
chromatography method. Piperacillin pharmacokinetics were calculated using a non
compartmental approach. In total, 212 piperacillin plasma concentrations were
determined. Median [interquartile range (IQR)] total piperacillin clearance was
7.5 (5.9-11.2) L/h in the CVVHDF group and 4.7 (4.5-9.6) L/h in the CVVH group (P
= 0.21). Median (IQR) piperacillin clearance related to continuous renal
replacement therapy (CRRT) was 3.0 (2.7-3.2) L/h in the CVVHDF group and 2.6 (1.9
3.0) L/h in the CVVH group (P = 0.29). Mean (standard deviation) steady state
concentrations were 68.4 (25.8) mg/L in the CVVHDF group and 89.1 (35.6) mg/L in
the CVVH group (P = 0.16). The estimated unbound concentrations resulting from
piperacillin continuous infusion were above the target susceptibility breakpoint
(16 mg/L) for the entire dosing interval (100% fT>MIC) in all study patients. In
the present study, higher (but not significantly) piperacillin clearance and
lower piperacillin exposure were observed in patients receiving CVVHDF compared
with CVVH. In patients receiving CRRT, the use of piperacillin continuous
infusion should be considered to ensure optimal exposure for less susceptible
pathogens.
PMID- 28689877
TI - A 10-year follow-up of bone mineral density in HIV-infected youths receiving
tenofovir disoproxil fumarate.
AB - BACKGROUND: The use of tenofovir disoproxil fumarate (TDF) has simplified the
antiretroviral regimen for HIV-infected patients and improved their compliance
with treatment, but it has been associated with decreased bone mineral density
(BMD) in adult patients, and data in pediatric patients are debated. The aim of
the current study was to assess the long-term effect of TDF on BMD in young
patients. METHODS: BMD was measured at the lumbar spine and in the whole skeleton
in 26 HIV-infected youths (13 female and 13 male, aged 5 to 17 years at
baseline). BMD was measured yearly for 10 years as part of standard care. BMD
changes were compared with those calculated from 202 healthy subjects aged 3 to
24 years. FINDINGS: All patients had good control of the infection during the 10
year study. BMD measurements changed significantly (P <0 ? 0001) in HIV-infected
youths. The mean annual BMD increment at the lumbar spine was 0 ? 046 (0 ? 006)
g/cm2 and 0 ? 042 (0 ? 006) g/cm2 in males and females, respectively. The
differences between the slopes of patients and healthy controls were not
significant. The annual BMD increment of the whole skeleton was 0 ? 030 (0 ? 005)
g/cm2 in males and 0 ? 019 (0 ? 004) g/cm2 in females. The slopes of BMD changes
of patients and healthy controls did not differ significantly. INTERPRETATION:
These data indicate that treatment with a TDF-containing antiretroviral regimen
does not impair BMD in young patients with HIV-infection. Larger studies are
needed to confirm these results.
PMID- 28689878
TI - Systematic review of antimicrobial lock therapy for prevention of central-line
associated bloodstream infections in adult and pediatric cancer patients.
AB - BACKGROUND: Central venous catheter (CVC) use is commonplace in cancer patients.
Antimicrobial lock therapy (ALT), the instillation of a concentrated
antimicrobial solution into the catheter lumen, is one method for preventing
infection among CVCs. This systematic review discusses the effectiveness and
safety of prophylactic ALT in cancer patients with CVCs. METHODS: A literature
search was performed using the Medline database and Google Scholar from inception
until April 2016. The following terms were used: 'antimicrobial lock solution',
'antibiotic lock solution', 'oncology', 'hematology', 'pediatrics', 'prevention',
'cancer', 'catheter related bloodstream infections', 'central-line associated
bloodstream infection' (CLABSI) and 'central venous catheter'. Studies evaluating
prophylactic ALT in cancer patients alone were eligible for inclusion. Case
reports, case series and in-vitro studies were excluded. RESULTS: In total, 78
articles were identified. Following all exclusions, 13 articles (three adult and
10 pediatric) were selected for evaluation. The most common agents utilized were
vancomycin with heparin; ethanol; taurolidine; and minocycline with EDTA. Quality
of evidence was moderate to high in adult studies and low to moderate in
pediatric studies. Use of ALT decreased the incidence of CLABSI in the majority
of studies; however, there were significant differences in definitions of CVC
related infection, dwell times and lock solutions. CONCLUSION: Lock therapy may
be an adjunct in high-risk cancer patients for the prevention of CLABSI; higher
quality evidence is needed for specific ALT recommendations.
PMID- 28689879
TI - Nonstandard Lumbar Region in Predicting Fracture Risk.
AB - Femoral neck (FN) bone mineral density (BMD) is the most commonly used skeletal
site to estimate fracture risk. The role of lumbar spine (LS) BMD in fracture
risk prediction is less clear due to osteophytes that spuriously increase LS BMD,
particularly at lower levels. The aim of this study was to compare fracture
predictive ability of upper L1-L2 BMD with standard L2-L4 BMD and assess whether
the addition of either LS site could improve fracture prediction over FN BMD.
This study comprised a prospective cohort of 3016 women and men over 60 yr from
the Dubbo Osteoporosis Epidemiology Study followed up for occurrence of minimal
trauma fractures from 1989 to 2014. Dual-energy X-ray absorptiometry was used to
measure BMD at L1-L2, L2-L4, and FN at baseline. Fracture risks were estimated
using Cox proportional hazards models separately for each site. Predictive
performances were compared using receiver operating characteristic curve
analyses. There were 565 women and 179 men with a minimal trauma fracture during
a mean of 11 +/- 7 yr. L1-L2 BMD T-score was significantly lower than L2-L4 T
score in both genders (p < 0.0001). L1-L2 and L2-L4 BMD models had a similar
fracture predictive ability. LS BMD was better than FN BMD in predicting
vertebral fracture risk in women [area under the curve 0.73 (95% confidence
interval, 0.68-0.79) vs 0.68 (95% confidence interval, 0.62-0.74), but FN was
superior for hip fractures prediction in both women and men. The addition of L1
L2 or L2-L4 to FN BMD in women increased overall and vertebral predictive power
compared with FN BMD alone by 1% and 4%, respectively (p < 0.05). In an elderly
population, L1-L2 is as good as but not better than L2-L4 site in predicting
fracture risk. The addition of LS BMD to FN BMD provided a modest additional
benefit in overall fracture risk. Further studies in individuals with spinal
degenerative disease are needed.
PMID- 28689880
TI - Characterization of CRF1 receptor antagonists with differential peripheral vs
central actions in CRF challenge in rats.
AB - The aim of this study was to investigate peripheral and central roles of
corticotropin-releasing factor (CRF) in endocrinological and behavioral changes.
Plasma adrenocorticotropin (ACTH) concentration was measured as an activity of
hypothalamic-pituitary-adrenal (HPA) axis. As behavioral changes, locomotion and
anxiety behavior were measured after CRF challenge intravenously (i.v.) for the
peripheral administration or intracerebroventricularly (i.c.v.) for the central
administration. Plasma ACTH concentration was significantly increased by both
administration routes of CRF; however, hyperlocomotion and anxiety behavior were
induced only by the i.c.v. administration. In the drug discovery of CRF1 receptor
antagonists, we identified two types of compounds, Compound A and Compound B,
which antagonized peripheral CRF-induced HPA axis activation to the same extent,
but showed different effects on the central CRF signal. These had similar in
vitro CRF1 receptor binding affinities (15 and 10nM) and functional activities in
reporter gene assay (15 and 9.5nM). In the ex vivo binding assays using tissues
of the pituitary, oral treatment with Compound A and Compound B at 10mg/kg
inhibited [125I]-CRF binding, whereas in the assay using tissues of the frontal
cortex, treatment of Compound A but not Compound B inhibited [125I]-CRF binding,
indicating that only Compound A inhibited central [125I]-CRF binding. In the
peripheral CRF challenge, increase in plasma ACTH concentration was significantly
suppressed by both Compound A and Compound B. In contrast, Compound A inhibited
the increase in locomotion induced by the central CRF challenge while Compound B
did not. Compound A also reduced central CRF challenge-induced anxiety behavior
and c-fos immunoreactivity in the cortex and the hypothalamic paraventricular
nucleus. These results indicate that the central CRF signal, rather than the
peripheral CRF signal would be related to anxiety and other behavioral changes,
and CRF1 receptor antagonism in the central nervous system may be critical for
identifying drug candidates for anxiety and mood disorders.
PMID- 28689881
TI - Comparison of radium-228 determination in water among Australian laboratories.
AB - The National Health and Medical Research Council and Natural Resource Management
Ministerial Council of Australia developed the current Australian Drinking Water
Guidelines which recommend an annual radiation dose value of 1 mSv year-1. One of
the potential major contributors to the radiation dose from drinking water is
radium-228, a naturally occurring radionuclide arising from the thorium decay
series. Various methods of analysing for radium-228 in water have been
established and adapted by analytical radiochemistry laboratories. Seven
laboratories in Australia participated in analysing radium-228 spiked water
samples with activity concentrations ranging from 6 mBq L-1 to 20 Bq L-1. The aim
of the exercise was to compare and evaluate radium-228 results reported by the
participating laboratories, the methods used and the detection limits. This paper
presents the outcome of the exercise.
PMID- 28689882
TI - Fatal haemorrhage following FNA
PMID- 28689883
TI - Currarino syndrome: does the presence of a genetic anomaly correlate with a more
severe phenotype? A multicentre study.
AB - BACKGROUND/PURPOSE: Currarino syndrome (CS) phenotype, initially described as the
triad of hemisacrum, anorectal malformation (ARM) and presacral mass, can be
extremely variable. The triad is often incomplete and 3 main CS phenotypical
subtypes have been described: Complete, Mild and Minimal. Various associated
malformations are often present. Mutations in the MNX1 gene are the main genetic
background of CS, although they are not present in almost half of the cases. Aim
of our study is to analyze the distribution of the 3 CS subtypes and the
incidence of associated malformations in a large sample of patients and to add
information about the role of the genetic testing in guiding the diagnostic and
prognostic evaluation of CS patients. METHODS: A multicentre retrospective data
collection was performed. CS patients' phenotype was accurately analyzed
according to a diagnostic-therapeutic standardized data collection sheet. The
distribution of the three CS types and the frequency of each associated
malformation were calculated. The phenotype of the patients with a known genetic
anomaly was compared to the phenotype of the population with no genetic
diagnosis, in order to determine whether the presence of a known genetic defect
could correlate with a more severe CS phenotype. RESULTS: Data from 45 patients
were analyzed. Twenty patients (44.5%) presented a Complete CS type, 19 (42.2%) a
Mild CS and 6 (13.3%) a Minimal CS. In addition to the classical triad elements,
38 (84.5%) patients showed associated anomalies. The group of patients who
resulted positive for a MNX1 mutation comprised a higher number (56.5%) of
Complete CS cases than the group of patients that did not carry any MNX1 mutation
(13%) (p = 0.0085). We could not find any relationship between CS subtype and the
number of associated anomalies (p = 0.5102). CONCLUSIONS: The presence of a MNX1
mutation seems to correlate with a more severe CS phenotype. MNX1 seems the main
responsible for the expression and the severity of the CS triad, while the
associated anomalies appear to be prevalently determined by genes sited on
different loci. A thorough multidisciplinary diagnostic overview of CS patients
should always include genetic counseling and analysis, both in postnatal and
prenatal settings. TYPE OF STUDY: Retrospective Study. LEVEL OF EVIDENCE: II.
PMID- 28689884
TI - Why wait: early enteral feeding after pediatric gastrostomy tube placement.
AB - PURPOSE: Early initiation of feedings after gastrostomy tube (GT) placement may
reduce associated hospital costs, but many surgeons fear complications could
result from earlier feeds. We hypothesized that, irrespective of placement
method, starting feedings within the first 6h following GT placement would not
result in a greater number of post-operative complications. METHODS: An IRB
approved retrospective review of all GTs placed between January 2012 and December
2014 at three academic institutions was undertaken. Data was stratified by
placement method and whether the patient was initiated on feeds at less than 6h
or after. Baseline demographics, operative variables, post-operative management
and complications were analyzed. Descriptive statistics were used and P-values
<0.05 were considered significant. RESULTS: One thousand and forty-eight patients
met inclusion criteria. GTs were inserted endoscopically (48.9%),
laparoscopically (44.9%), or via an open approach (6.2%). Demographics were
similar in early and late fed groups. When controlling for method of placement,
those patients who were fed within the first 6h after gastrostomy placement had
shorter lengths of stay compared to those fed greater than 6h after placement
(P<0.05). Total post-operative outcomes were equivalent between feeding groups
for all methods of placement (laparoscopic (P=0.87), PEG (P=0.94), open
(P=0.81)). CONCLUSIONS: Early initiation of feedings following GT placement was
not associated with an increase in complications. Feeds initiated earlier may
shorten hospital stays and decrease overall hospital costs. TYPE OF STUDY: Multi
institutional retrospective. LEVEL OF EVIDENCE: III.
PMID- 28689885
TI - Reduction of hydrogen sulfide synthesis enzymes cystathionine-beta-synthase and
cystathionine-gamma-lyase in the colon of patients with Hirschsprungs disease.
AB - PURPOSE: Hirschsprung associated enterocolitis (HAEC) is the most common cause of
morbidity and mortality in Hirschsprung Disease (HSCR). The pathogenesis of HAEC
is poorly understood. In recent years, there is increasing evidence that a
compromised intestinal barrier function plays a major role in the pathogenesis of
HAEC. Hydrogen sulfide, synthesized from L-cysteine by two key enzymes,
cystathionine-beta-synthase (CBS) and cystathionine-gamma-lysase (CSE) is
reported to play a key role in regulating gastrointestinal motility and promoting
resolution of inflammation. We designed this study to test the hypothesis that
CBS and CSE expression is altered in the colon of patients with HSCR. METHODS: We
investigated CBS and CSE protein expression in both the aganglionic and
ganglionic regions of HSCR patients (n=10) versus healthy control colon (n=10).
Protein distribution was assessed by using immunofluorescence and confocal
microscopy. Gene and protein expression was quantified using quantitative real
time polymerase chain reaction (qPCR), Western blot analysis, and densitometry.
MAIN RESULTS: qPCR and Western blot analysis revealed that CBS and CSE are
expressed in the normal human colon. CBS and CSE expression was significantly
decreased (p<0.003) in the ganglionic and aganglionic bowel in HSCR compared to
controls. Confocal microscopy revealed that CBS and CSE expression in smooth
muscles, interstitial cells of Cajal, platelet-derived growth factor-alpha
receptor-positive cells, enteric neurons and colonic epithelium was markedly
decreased in HSCR specimens compared to controls. CONCLUSION: We demonstrate for
the first time the expression and distribution of CBS/CSE in patients with HSCR.
The observed decreased expression of CBS and CSE may affect mucosal integrity and
colonic contractility and thus render HSCR patients more susceptible to develop
HAEC.
PMID- 28689886
TI - Use of radiotracer labeling of pulmonary nodules to facilitate excisional biopsy
and metastasectomy in children with solid tumors.
AB - PURPOSE: Excision of suspected pulmonary metastases in children is challenging in
the setting of multiple nodules or nodules that are small, deep, or soft. This
study describes preoperative technetium macro-aggregated albumin (Tc 99m MAA)
localization of pulmonary lesions to aid in intraoperative identification and
resection. METHODS: Patients with past or present pediatric solid tumors who
underwent resection of pulmonary nodules following CT-guided Tc 99m MAA labeling
were identified. The primary outcomes were successful preoperative localization
and subsequent resection. RESULTS: Metastasectomy following Tc 99m MAA
localization was performed 15 times in 11 patients from 2014 to 2016. Mean age
was 13years; the most common diagnosis was osteosarcoma (33%). Tc 99m MAA
labeling was attempted in 24 nodules with mean nodule diameter 6+/-5mm and mean
depth from the pleural surface of 12+/-17mm; localization was successful in 23
nodules (96%). Subsequent resection was performed by thoracotomy in 12 cases and
thoracoscopy in 3. All labeled nodules were identified intraoperatively; two were
not resected and 17 of the 21 nodules resected demonstrated metastatic disease on
pathology. CONCLUSION: Tc 99m MAA labeling of pulmonary nodules in children is
effective in facilitating resection of sub-centimeter intraparenchymal metastases
identified on preoperative imaging. Furthermore, this technique allows for
thoracoscopic metastasectomy in select patients. TYPE OF STUDY/LEVEL OF EVIDENCE:
Case Series/Level IV.
PMID- 28689887
TI - CO2 laser cauterization approach to congenital pyriform sinus fistula.
AB - OBJECTIVE: To evaluate the efficacy of CO2 laser cauterization with suspension
microlaryngoscopy as a definitive surgical treatment for pediatric Congenital
Pyriform Sinus Fistula (CPSF). MATERIAL AND METHODS: This is a cohort
retrospective study. Thyroid function and cervical ultrasonography examinations
were performed before operation. Enhanced magnetic resonance imaging (MRI) was
performed on patients with a repeated infection (>=2 times) and/or if they had a
prior open surgery. Patients were divided into two groups: the <8-year-old group
and the >=8-year-old group. The differences in the number of cauterization
procedures between the two age groups and between the initial treatment and the
retreatment groups were analyzed. RESULTS: CO2 laser cauterizations with
suspension microlaryngoscopy were performed for 104 CPSF patients. No
complications occurred. Three patients had a recurrence in the follow-up. The
number of surgical cauterization operations was fewer than 3 in 85.1% of the
patients. There was no significant difference in the number of cauterizations
among the different age groups or between the initial treatment and retreatment
groups (P>0.05). CONCLUSION: CO2 laser cauterization with suspension
microlaryngoscopy is a safe, effective, and minimally invasive approach to CPSF
with optimal patient outcomes. TYPE OF STUDY: Treatment Study. LEVEL OF EVIDENCE:
Level III.
PMID- 28689888
TI - Polyurethane versus silicone port a cath: What's going on at removal?
AB - BACKGROUND: Port-a-cath (PAC) is an essential device in the management of the
patients of chronic illness, but despite theirs benefits there are many
complications either at the time of insertion or at time of removal. Our aim of
this study is to evaluate the fracture rate of the catheter at removal time in
comparison with catheter type either polyurethane or silicone. METHODS: A
retrospective monocentric study of all PACs which were removed at our university
pediatric hospital between 1 January 2006 and 31 December 2016. Two groups were
compared: polyurethane group and silicone group. RESULTS: Total of 216 central
lines were removed, the mean age at the time of extraction was 9.7+/-4.9years and
the mean time for both catheter was 2.7+/-1.6years, fracture occurred in 11
catheter of the polyurethane group (n=119), with no fracture of silicone group
(n=86), in the polyurethane group, the risk of catheter fracture is significantly
related to the duration of the PAC in place. CONCLUSION: We found that the
polyurethane-based catheters are more vulnerable for rupture and retained
fragment in the blood vessels, especially if left in place for long time, for
this reason we have switched to silicone-based catheter and all catheters should
be remove within duration maximal of 2years. TYPE OF STUDY: Prognosis study.
LEVEL OF EVIDENCE: Level II.
PMID- 28689889
TI - Independent channels for miRNA biosynthesis ensure efficient static and dynamic
control in the regulation of the early stages of myogenesis.
AB - Motivated by recent experimental work, we define and study a deterministic model
of the complex miRNA-based regulatory circuit that putatively controls the early
stage of myogenesis in human. We aim in particular at a quantitative
understanding of (i) the roles played by the separate and independent miRNA
biosynthesis channels (one involving a miRNA-decoy system regulated by an
exogenous controller, the other given by transcription from a distinct genomic
locus) that appear to be crucial for the differentiation program, and of (ii) how
competition to bind miRNAs can efficiently control molecular levels in such an
interconnected architecture. We show that optimal static control via the miRNA
decoy system constrains kinetic parameters in narrow ranges where the channels
are tightly cross-linked. On the other hand, the alternative locus for miRNA
transcription can ensure that the fast concentration shifts required by the
differentiation program are achieved, specifically via non-linear response of the
target to even modest surges in the miRNA transcription rate. While static,
competition-mediated regulation can be achieved by the miRNA-decoy system alone,
both channels are essential for the circuit's overall functionality, suggesting
that that this type of joint control may represent a minimal optimal architecture
in different contexts.
PMID- 28689890
TI - The dose-dense principle in chemotherapy.
AB - Chemotherapy is a cancer treatment modality that uses drugs to kill tumor cells.
A typical chemotherapeutic protocol consists of several drugs delivered in cycles
of three weeks. We present mathematical analyses demonstrating the existence of a
maximum time between cycles of chemotherapy for a protocol to be effective. A
mathematical equation is derived, which relates such a maximum time with the
variables that govern the kinetics of the tumor and those characterizing the
chemotherapeutic treatment. Our results suggest that there are compelling
arguments supporting the use of dose-dense protocols. Finally, we discuss the
limitations of these protocols and suggest an alternative.
PMID- 28689891
TI - Collective strategies and cyclic dominance in asymmetric predator-prey spatial
games.
AB - Predators may attack isolated or grouped prey in a cooperative, collective way.
Whether a gregarious behavior is advantageous to each species depends on several
conditions and game theory is a useful tool to deal with such a problem. We here
extend the Lett et al. (2004) to spatially distributed populations and compare
the resulting behavior with their mean-field predictions for the coevolving
densities of predator and prey strategies. Besides its richer behavior in the
presence of spatial organization, we also show that the coexistence phase in
which collective and individual strategies for each group are present is stable
because of an effective, cyclic dominance mechanism similar to a well-studied
generalization of the Rock-Paper-Scissors game with four species, a further
example of how ubiquitous this coexistence mechanism is.
PMID- 28689892
TI - Corrigendum to Aetiology, pathogenesis, and specific management of Stahl's ear:
role of the transverse muscle insertion: [British journal of Oral and
Maxillofacial Surgery 51/8 (2013) e230-233].
PMID- 28689893
TI - Evaluation of serological and molecular tests used to identify Toxoplasma gondii
infection in pregnant women attended in a public health service in Sao Paulo
state, Brazil.
AB - Toxoplasmosis during pregnancy can have severe consequences. The use of sensitive
and specific serological and molecular methods is extremely important for the
correct diagnosis of the disease. We compared the ELISA and ELFA serological
methods, conventional PCR (cPCR), Nested PCR and quantitative PCR (qPCR) in the
diagnosis of Toxoplasma gondii infection in pregnant women without clinical
suspicion of toxoplasmosis (G1=94) and with clinical suspicion of toxoplasmosis
(G2=53). The results were compared using the Kappa index, and the sensitivity,
specificity, positive predictive value and negative predictive value were
calculated. The results of the serological methods showed concordance between the
ELISA and ELFA methods even though ELFA identified more positive cases than
ELISA. Molecular methods were discrepant with cPCR using B22/23 primers having
greater sensitivity and lower specificity compared to the other molecular
methods.
PMID- 28689894
TI - Urine concentrations of human beta-defensins and ribonuclease 7 in urinary tract
infection and asymptomatic bacteriuria.
AB - Antimicrobial peptides (AMPs) provide a first line of defense against bacterial
infections. Here we report that urine levels of AMPs, locally produced in the
urinary tract, are lower in individuals with asymptomatic bacteriuria (ABU)
compared to patients with urinary tract infection (UTI).
PMID- 28689895
TI - Plasmid-mediated transfer of CTX-M-55 extended-spectrum beta-lactamase among
different strains of Salmonella and Shigella spp. in the Republic of Korea.
AB - We screened 10 CTX-M-55-producing Shigella and Salmonella isolates from a
national surveillance in Korea. The blaCTX-M-55 was located on the IncI1 (n=5),
IncA/C (n=4) and IncZ (n=1) plasmids, downstream of ISEcp1, IS26-ISEcp1 and
ISEcp1-IS5 sequences, respectively. These results indicate that CTX-M-55 has
disseminated to other bacteria by lateral plasmid transfer.
PMID- 28689896
TI - Blood cultures after bone biopsy in diabetic foot osteomyelitis.
AB - The value of blood cultures after bone biopsy in diabetic foot osteomyelitis was
assessed through a prospective monocentric study. Blood cultures tested positive
in 15.8% of patients. Risk factors were male gender, higher CRP levels,
Streptococcus sp.-positive bone culture, and pre-existing valvulopathy.
PMID- 28689897
TI - The Prevalence and Causes of Vision Loss in Indigenous and Non-Indigenous
Australians: The National Eye Health Survey.
AB - PURPOSE: To conduct a nationwide survey on the prevalence and causes of vision
loss in Indigenous and non-Indigenous Australians. DESIGN: Nationwide, cross
sectional, population-based survey. PARTICIPANTS: Indigenous Australians aged 40
years or older and non-Indigenous Australians aged 50 years and older. METHODS:
Multistage random-cluster sampling was used to select 3098 non-Indigenous
Australians and 1738 Indigenous Australians from 30 sites across 5 remoteness
strata (response rate of 71.5%). Sociodemographic and health data were collected
using an interviewer-administered questionnaire. Trained examiners conducted
standardized eye examinations, including visual acuity, perimetry, slit-lamp
examination, intraocular pressure, and fundus photography. The prevalence and
main causes of bilateral presenting vision loss (visual acuity <6/12 in the
better eye) were determined, and risk factors were identified. MAIN OUTCOME
MEASURES: Prevalence and main causes of vision loss. RESULTS: The overall
prevalence of vision loss in Australia was 6.6% (95% confidence interval [CI],
5.4-7.8). The prevalence of vision loss was 11.2% (95% CI, 9.5-13.1) in
Indigenous Australians and 6.5% (95% CI, 5.3-7.9) in non-Indigenous Australians.
Vision loss was 2.8 times more prevalent in Indigenous Australians than in non
Indigenous Australians after age and gender adjustment (17.7%, 95% CI, 14.5-21.0
vs. 6.4%, 95% CI, 5.2-7.6, P < 0.001). In non-Indigenous Australians, the leading
causes of vision loss were uncorrected refractive error (61.3%), cataract
(13.2%), and age-related macular degeneration (10.3%). In Indigenous Australians,
the leading causes of vision loss were uncorrected refractive error (60.8%),
cataract (20.1%), and diabetic retinopathy (5.2%). In non-Indigenous Australians,
increasing age (odds ratio [OR], 1.72 per decade) and having not had an eye
examination within the past year (OR, 1.61) were risk factors for vision loss.
Risk factors in Indigenous Australians included older age (OR, 1.61 per decade),
remoteness (OR, 2.02), gender (OR, 0.60 for men), and diabetes in combination
with never having had an eye examination (OR, 14.47). CONCLUSIONS: Vision loss is
more prevalent in Indigenous Australians than in non-Indigenous Australians,
highlighting that improvements in eye healthcare in Indigenous communities are
required. The leading causes of vision loss were uncorrected refractive error and
cataract, which are readily treatable. Other countries with Indigenous
communities may benefit from conducting similar surveys of Indigenous and non
Indigenous populations.
PMID- 28689898
TI - Corticosteroid-Related Adverse Events Systematically Increase with Corticosteroid
Dose in Noninfectious Intermediate, Posterior, or Panuveitis: Post Hoc Analyses
from the VISUAL-1 and VISUAL-2 Trials.
AB - PURPOSE: Chronic use of corticosteroids for the treatment of uveitis has been
linked with drug-associated toxicity and adverse events (AEs). This study
examines the association between corticosteroid dosage and incidence rates of
corticosteroid-related AEs. DESIGN: A post hoc analysis of the VISUAL-1 and
VISUAL-2 placebo-controlled clinical trials. PARTICIPANTS: The clinical trials
consisted of adults with active (VISUAL-1) and inactive (VISUAL-2) noninfectious
intermediate, posterior, and panuveitis. Patients were randomized to receive
adalimumab or placebo and underwent a protocol-defined mandatory taper to
discontinue their oral corticosteroids. METHODS: Adverse event data were
collected at each visit and included an assessment of the corticosteroid
relationship by the investigator. A longitudinal Poisson regression model was
estimated controlling for time-dependent corticosteroid dose, age, sex, prior
oral corticosteroid dose, prior topical corticosteroid use, and concomitant
immunosuppressive drug use. Only patients randomized to placebo were considered.
MAIN OUTCOME MEASURES: The primary outcome measure was the frequency of AEs.
RESULTS: The incidence rates of corticosteroid-related AEs among placebo patients
during the prednisone treatment period in VISUAL-1 was statistically higher than
after discontinuation (454.2 per 100 patient-years [PY] vs. 36.1 per 100 PY,
incident rate ratio = 12.6, P < 0.001). Incidence rate ratios among VISUAL-2
patients were similarly high (317.5 per 100 PY vs. 41.1 per 100 PY, incident rate
ratio = 7.7, P < 0.001). Based on the Poisson multivariate longitudinal
Generalized Estimating Equation (GEE) model, each 10 mg increase in prednisone
dose is associated with a 1.5- and 2.6-fold increase (P < 0.001 and P < 0.001) in
the rate of corticosteroid-related AEs in VISUAL-1 and VISUAL-2, respectively.
This implies in turn that a patient with active uveitis taking 60 mg/day of
prednisone will experience, on average, an additional 10.1 (95% confidence
interval (CI), 6.3-14.5; P < 0.001) corticosteroid-related AEs per year compared
with a patient taking 10 mg/day, whereas a patient with inactive uveitis taking
35 mg/day of prednisone will experience, on average, an additional 23.5 (95% CI,
7.6-52.7; P = 0.05) corticosteroid-related AEs per year compared with a patient
taking 10 mg/day. CONCLUSIONS: Evidence from VISUAL-1 and VISUAL-2 suggests that
the incidence rates of corticosteroid-related AEs increase systematically with
corticosteroid dose.
PMID- 28689899
TI - Maximising Recruitment to Randomised Controlled Trials: The Role of Qualitative
Research to Inform Recruitment Challenges.
PMID- 28689900
TI - Re: Sungmin Woo, Chong Hyun Suh, Sang Youn Kim, Jeong Yeon Cho, Seung Hyup Kim.
Diagnostic Performance of Magnetic Resonance Imaging for the Detection of Bone
Metastasis in Prostate Cancer: A Systematic Review and Meta-analysis. Eur Urol.
In press. http://dx.doi.org/10.1016/j.eururo.2017.03.042.
PMID- 28689901
TI - Effect of nonthermal plasma on the properties of a resinous liner submitted to
aging.
AB - STATEMENT OF PROBLEM: The properties, such as softness and viscoelasticity, of a
resinous reliner can deteriorate and extrinsic elements can become incorporated,
making surface protection of the reliner material essential. PURPOSE: The purpose
of this in vitro study was to evaluate the effect of low temperature plasma on
Coe-Soft resinous reliner, submitted to aging in artificial saliva for up to 180
days. Sorption, solubility, Shore A hardness, surface energy, and topographic
characteristics were analyzed by scanning electronic microscopy (SEM) and energy
dispersive spectroscopy (EDS). MATERIAL AND METHODS: Forty-four specimens were
fabricated and distributed in 2 groups: nonplasma reliner (control group) and
reliner with plasma (plasma group). The plasma was applied with a mixture of 70%
hexamethyldisiloxane, 20% O, and 10% Ar. Total work pressure was maintained at a
constant 20 Pa for 30 minutes of deposition. The specimens were analyzed before
and after aging in an incubator with immersion in artificial saliva for 30, 90,
and 180 days. The quantitative data were submitted to 2-way ANOVA and the Tukey
test (alpha=.05), while qualitative data were compared visually. RESULTS: The
control group presented lower Shore A hardness values only in the initial period,
and surface energy increased with aging for both groups until 90 days. Greater
sorption percentage values were encountered at 180 days in the plasma group.
Greater solubility values were encountered in the control group in all periods.
CONCLUSIONS: Plasma is an option for the protection of the material studied
because the deposited film remained on the surface of the reliner material after
aging.
PMID- 28689902
TI - Effect of layered manufacturing techniques, alloy powders, and layer thickness on
metal-ceramic bond strength.
AB - STATEMENT OF PROBLEM: Direct metal laser sintering (DMLS) and direct metal laser
melting (DMLM) have become popular for fabricating the metal frameworks of metal
ceramic restorations. How the type of layered manufacturing device, layer
thickness, and alloy powder may affect the bond strength of ceramic to metal
substructure is unclear. PURPOSE: The purpose of this in vitro study was to
evaluate the bond strength of dental porcelain to metal frameworks fabricated
using different layered manufacturing techniques (DMLS and DMLM), Co-Cr alloy
powders, and layer thicknesses and to evaluate whether a correlation exists
between the bond strength and the number of ceramic remnants on the metal
surface. MATERIAL AND METHODS: A total of 75 bar-shaped metal specimens (n=15)
were fabricated using either DMLS or DMLM. The powder alloys used were Keramit NP
S and EOS-Cobalt-Chrome SP-2 with layer thicknesses of 20 MUm and 30 MUm. After
ceramic application, the metal-ceramic bond strength was evaluated with a 3-point
bend test. Three-way ANOVA followed by the Tukey honest significance difference
test were used for statistical analysis (alpha=.05). De-bonding surface
microstructure was observed with scanning electron microscopy. Energy dispersive
spectroscopy analysis was conducted to evaluate the correlation between ceramic
remnants on the metal surface and bond strength values. RESULTS: The mean bond
strength value of DMLS was significantly higher than that of DMLM. While no
statistically significant difference was found between layer thicknesses, alloy
powders closely affected bond strength. Statistical comparisons revealed that the
highest bond strength could be achieved with DMLS-Cobalt-Chrome SP2-20MUm, and
the lowest bond strength was observed in DMLS-Keramit NP-S-20MUm (P<=.05). No
correlation was found between porcelain remnants on the metal surface and bond
strength values. CONCLUSIONS: The layered manufacturing device and the alloy
powders evaluated in the current study closely affected the bond strength of
dental porcelain to a metal framework. However, layer thickness did not affect
the bond strength.
PMID- 28689903
TI - Survival of 2039 complete arch fixed implant-supported zirconia prostheses: A
retrospective study.
AB - STATEMENT OF PROBLEM: Presently, data for the survival of 1-piece complete arch
fixed implant-supported zirconia prostheses are limited. PURPOSE: The purpose of
this retrospective study was to evaluate the survival outcomes of 1-piece
complete arch fixed implant-supported zirconia prostheses fabricated by a single
dental laboratory supporting several clinicians. MATERIAL AND METHODS: Outcome
data were collected over a 5-year period from a large commercial dental
laboratory that fabricated 2039 1-piece complete arch fixed implant-supported
monolithic zirconia prostheses. All prostheses were fabricated using the same
zirconia system from 1 manufacturer, using standardized protocols. The zirconia
prostheses were predominantly monolithic, with veneered porcelain restricted to
the gingival region. Because a 5-year warranty against fracture was offered by
this dental laboratory, prostheses that were returned to the laboratory for
remake because of catastrophic failure (fracture) or technical complications were
identified, and data were analyzed using a life table. RESULTS: Of the 2039
zirconia prostheses evaluated, at least 319 prostheses had a minimum of 3 years
of clinical service, and 69 prostheses had a minimum of 4 years of clinical
service. A total of 6 fractures were reported, resulting in a first-year interval
survival rate of 99.8% and a 5-year cumulative survival rate of 99.3%. Six
zirconia prostheses were returned to the laboratory during the 5-year period
because of technical complications related to the debonding of titanium
cylinders, and 3 prostheses were returned because of fracture of the titanium
cylinders. No prostheses were returned because of chipping of the veneered
gingival porcelain. CONCLUSIONS: Practice-based evidence from this large sample,
short-term retrospective study showed that 1-piece complete arch fixed implant
supported zirconia prostheses with veneered porcelain restricted to the gingival
region showed a cumulative survival rate of 99.3% in a 5-year period. The
technical complication rate related to this type of prosthesis was minimal.
PMID- 28689904
TI - Correlation between iris diameter and the width of the maxillary central incisor
with digital image analysis.
AB - STATEMENT OF PROBLEM: Various methods have been suggested for determining the
width of maxillary anterior teeth for complete dentures. A straightforward and
reliable technique for anterior tooth selection in complete denture is still
needed. PURPOSE: The purpose of this clinical study was to determine the
correlation between the horizontal visible iris diameter (HVID) of the eye and
the mesiodistal width of the maxillary central incisor tooth in a dentate Indian
population. MATERIAL AND METHODS: One hundred Indian dental students participated
in this study. A standardized image of the face revealing the eyes and teeth on
smile was captured. The measurements of the HVID and the mesiodistal width of the
maxillary central incisor at the cervical third, middle third, and incisal edge
were evaluated with photoimaging software. The data were subjected to statistical
analysis by paired-sample t test to compare the right and left sides, independent
sample t tests to compare between sexes, and the Pearson correlation coefficient
(r) to investigate the association between variables (alpha=.05) RESULTS: A
positive correlation between the HVID and the mesiodistal width of the maxillary
central incisor was found in men, with r values of .62, .78, and .79 in the
cervical, middle, and incisal third regions, respectively. In women, respective r
values of .59, .73, and .75 were found. Minimal differences were observed between
right- and left-side measurements. CONCLUSIONS: The HVID of the eyes can be used
to estimate the mesiodistal width of the maxillary central incisor tooth.
PMID- 28689905
TI - Proinflammatory cytokine production from NOK-SI keratinocytes after exposure to
denture adhesives.
AB - STATEMENT OF PROBLEM: Although the cytotoxicity of denture adhesives has been
widely assessed, data on the release of proinflammatory cytokines from oral
epithelial cells are still scarce. PURPOSE: The purpose of this in vitro study
was to evaluate the proinflammatory cytokines interleukin (IL) 1beta, IL-6, and
tumor necrosis factor alpha (TNF-alpha) released from human oral keratinocytes
after exposure to denture adhesives. MATERIAL AND METHODS: Eluates of the Ultra
Corega cream, Corega powder Fixador Ultra, and Corega strip denture adhesives
were created at 1% wt/vol after 24 hours of exposure in a Dulbecco modified Eagle
medium culture. The release of IL-1beta, IL-6, and TNF-alpha was measured using a
sandwich enzyme-linked immunosorbent assay after the oral epithelial cells (NOK
SI) had been exposed to the eluates for 3, 6, and 24 hours (n=6). RESULTS: IL
1beta release from the strip was higher at 3 hours compared with the control
(Bonferroni post hoc test, P=.016). IL-6 releases from the cream and powder
denture adhesives at 6 and 24 hours were higher than for the controls (Bonferroni
post hoc test, P<.05). TNF-alpha release was not detectable in some groups and
periods. CONCLUSIONS: In long periods, denture adhesive strips do not induce any
change on cytokine release from human oral keratinocytes.
PMID- 28689906
TI - Comparison of digital intraoral scanner reproducibility and image trueness
considering repetitive experience.
AB - STATEMENT OF PROBLEM: Because the digital workflow can begin directly in the oral
cavity, intraoral scanners are being adopted in dental treatments. However,
studies of the relationship between the experience of the practitioner and the
accuracy of impression data are needed. PURPOSE: The purpose of this clinical
study was to investigate the effect of the experience curve on changes in
trueness when a patient's complete dental arch is scanned. MATERIAL AND METHODS:
Twenty dental hygienists with more than 3 years of experience in dental clinical
practice (group 1 had 3 to 5 years; group 2 had >6 years) were recruited to learn
to operate 2 intraoral scanner systems. All learners scanned the assigned
patient's oral cavity 10 times during the experience sessions. Precision was
calculated as the mean deviation among all superimposition combinations from the
10 scanned data sets of each learner [n=10C2=45]. Trueness was evaluated by
superimposing the 10 consecutive intraoral scan data onto the impression scan
data from each patient's rubber impression body (n=10). The acquired images were
processed and analyzed using a 3-dimensional analysis software. For statistical
analysis, the independent 2-sample t test and repeated measures ANOVA were
performed (alpha=.05). RESULTS: The mean precision of the Trios scanner was
greater than that of the iTero (Trios, 52.30 MUm; iTero, 60.46 MUm; P<.01). The
iTero group showed an improvement in trueness upon repeated experience (P<.05),
whereas the Trios group did not (P>.05). In the iTero group but not in the Trios
group, the length of clinical experience influenced the change of trueness as a
result of repeated experience (P<.05). In terms of the scanned region, the
results for trueness were better for the maxillary arch than the mandibular arch
with repeated scanning in the iTero group (P<.05). CONCLUSIONS: The single-image
based system required repeated learning sessions for effective clinical
application. The newer system offered better trueness and precision and was less
likely to be influenced by the length of clinical career or the region being
scanned.
PMID- 28689907
TI - A digitally guided dual technique for both gingival and bone resection during
crown lengthening surgery.
AB - This paper presents a digitally guided dual technique that provides references
for gingival and bone resection during crown lengthening surgery. The
architecture of the teeth, gingiva, and alveolar bone is scanned and registered
to design dual guides consisting of a gingivectomy guide and an alveolectomy
guide that are used in periodontal surgery for esthetic rehabilitation.
PMID- 28689908
TI - The insertion torque-depth curve integral as a measure of implant primary
stability: An in vitro study on polyurethane foam blocks.
AB - STATEMENT OF PROBLEM: Recent research has shown that dynamic parameters correlate
with insertion energy-that is, the total work needed to place an implant into its
site-might convey more reliable information concerning immediate implant primary
stability at insertion than the commonly used insertion torque (IT), the reverse
torque (RT), or the implant stability quotient (ISQ). Yet knowledge on these
dynamic parameters is still limited. PURPOSE: The purpose of this in vitro study
was to evaluate whether an energy-related parameter, the torque-depth curve
integral (I), could be a reliable measure of primary stability. This was done by
assessing if (I) measurement was operator-independent, by investigating its
correlation with other known primary stability parameters (IT, RT, or ISQ) by
quantifying the (I) average error and correlating (I), IT, RT, and ISQ variations
with bone density. MATERIAL AND METHODS: Five operators placed 200 implants in
polyurethane foam blocks of different densities using a micromotor that
calculated the (I) during implant placement. Primary implant stability was
assessed by measuring the ISQ, IT, and RT. ANOVA tests were used to evaluate
whether measurements were operator independent (P>.05 in all cases). A
correlation analysis was performed between (I) and IT, ISQ, and RT. The (I)
average error was calculated and compared with that of the other parameters by
ANOVA. (I)-density, IT-density, ISQ-density, and RT-density plots were drawn, and
their slopes were compared by ANCOVA. RESULTS: The (I) measurements were operator
independent and correlated with IT, ISQ, and RT. The average error of these
parameters was not significantly different (P>.05 in all cases). The (I)-density,
IT-density, ISQ-density, and RT-density curves were linear in the 0.16 to 0.49
g/cm3 range, with the (I)-density curves having a significantly greater slope
than those regarding the other parameters (P<=.001 in all cases). CONCLUSIONS:
The torque-depth curve integral (I) provides a reliable assessment of primary
stability and shows a greater sensitivity to density variations than other known
primary stability parameters.
PMID- 28689909
TI - Effects of core and veneer thicknesses on the color of CAD-CAM lithium disilicate
ceramics.
AB - STATEMENT OF PROBLEM: The color of dental ceramics is important for achieving
successful esthetic restorations. However, insufficient studies are available of
the color of recently introduced computer-aided design-computer-aided
manufacturing (CAD-CAM) lithium disilicate ceramics as functions of the core and
veneer thicknesses. PURPOSE: The purpose of this in vitro study was to evaluate
the effects of the thickness of different core and veneer thicknesses on the
color of CAD-CAM lithium disilicate ceramics. MATERIAL AND METHODS: A total of 42
specimens from 2 groups of 7 ceramic cores at 3 thicknesses (0.8, 1.0, and 1.2
mm) were fabricated. The veneer was fabricated at 3 thicknesses (0.3, 0.5, and
0.7 mm). The group name was based on the name of the ceramic core (IPS e.max CAD;
lithium disilicate [LD], IPS Empress CAD; leucite-reinforced glass-ceramic [LR]),
and the associated number was determined by the combined thicknesses of the core
and the veneer: 1=0.8+0.7; 2=1.0+0.5; and 3=1.2+0.3. The color coordinates and
the color differences were calculated using a spectrophotometer. The color
difference was analyzed using the CIEDE2000 chrominance and the acceptability
threshold. Two-way ANOVA was used to identify the color difference based on the
core/veneer thicknesses, and the Tukey honest significant differences and Games
Howell tests were conducted to verify the DeltaE00 differences of the group
(alpha=.05). In addition, regression analysis was carried out to estimate the
causal relationship between the independent variables and the chrominance.
RESULTS: At a certain thickness, the color differences of LD1, LR1, and LR2 were
not clinically acceptable based on the thicknesses of the core and the veneer.
Results of 2-way ANOVA demonstrated that the different thicknesses of core/veneer
combination significantly affected the color difference (P<.05). A significant
interaction was present between the thickness and the material (P<.05). The
results of multiple regression analyses showed that the average color difference
of LR increased by 0.019 as the thickness of the core decreased by 0.2 mm.
CONCLUSIONS: The color is influenced by the thicknesses of the core and the
veneer. With a certain thickness, the color differences increased as the
thickness of the core decreased, and lithium disilicate ceramics were less
vulnerable to standard deviation of color difference compared with the leucite
reinforced ceramics.
PMID- 28689910
TI - Management of postburn perioral contracture using a customized static commissural
splint and intralesional injections of triamcinolone.
AB - A perioral facial burn is usually accompanied by a reduction in size of the oral
orifice because of the contraction of the healing wound. Perioral contracture
leads to microstomia, restricting nutrition, speech, and jaw movements and
impairing the esthetic appearance of the face. It is imperative to introduce
splints as early as possible to prevent the postburn sequelae. A delay in
splinting allows postburn contractures. Overcoming these contractures to regain
the size of the stoma requires restructuring of the hypertrophic scar using
mechanical force and the biomodification of the tissues. This article describes
the treatment of microstomia and the hypertrophic scarring of the perioral tissue
using a novel static commissural splint with customizable components in
conjunction with intralesional injections of triamcinolone. Within 6 months, the
splint together with the steroid injections had helped increase the vertical
opening of the mouth by 15 mm and the intercommissural distance by 16 mm.
PMID- 28689911
TI - Effect of grinding and polishing on roughness and strength of zirconia.
AB - STATEMENT OF PROBLEM: The clinical applications of high-translucency monolithic
zirconia restorations have increased. Chairside and laboratory adjustments of
these restorations are inevitable, which may lead to increased roughness and
reduced strength. The influence of grinding and polishing on high-translucency
zirconia has not been investigated. PURPOSE: The purpose of this in vitro study
was to compare the roughness averages (Ra) of ground and polished zirconia and
investigate whether roughness influenced strength after aging. MATERIAL AND
METHODS: High-translucency zirconia disks were milled, sintered, and glazed
according to the manufacturer's recommendations. Specimens were randomized to 4
equal groups. Group G received only grinding; groups GPB and GPK received
grinding and polishing with different polishing systems; and group C was the
(unground) control group. All specimens were subjected to hydrothermal aging in
an autoclave at 134 degrees C at 200 kPa for 3 hours. Roughness average was
measured using a 3-dimensional (3D) optical interferometer at baseline (Ra1),
after grinding and polishing (Ra2), and after aging (Ra3). A biaxial flexural
strength test was performed at a rate of 0.5 mm/min. Statistical analyses were
performed using commercial software (alpha=.05). RESULTS: Group G showed a
significantly higher mean value of Ra3 (1.96 +/-0.32 MUm) than polished and
glazed groups (P<.001), which showed no statistically significant difference
among them (GPB, 1.12 +/-0.31 um; GPK, 0.88 +/-0.31 um; C: 0.87 +/-0.25 MUm)
(P>.05). Compared with baseline, the roughness of groups G and GPB increased
significantly after surface treatments and after aging, whereas aging did not
significantly influence the roughness of groups GPK or C. Group G showed the
lowest mean value of biaxial flexural strength (879.01 +/-157.99 MPa), and the
highest value was achieved by group C (962.40 +/-113.84 MPa); no statistically
significant differences were found among groups (P>.05). Additionally, no
significant correlation was detected between the Ra and flexural strength of
zirconia. CONCLUSIONS: Grinding increased the roughness of zirconia restorations,
whereas proper polishing resulted in smoothness comparable with glazed surfaces.
The results provide no evidence that grinding and polishing affect the flexural
strength of zirconia after aging.
PMID- 28689912
TI - Influence of scanner, powder application, and adjustments on CAD-CAM crown
misfit.
AB - STATEMENT OF PROBLEM: The manufacturers of computer-aided design and computer
aided manufacturing (CAD-CAM) systems emphasize that new technologies can improve
the marginal fit of dental crowns. However, data supporting this claim are
limited. PURPOSE: The purpose of this in vitro study was to investigate the
differences among the following fabrication methods on the marginal discrepancy
of dental crowns: intraoral optical scanners, powder application, and adjustments
of intaglio surface. MATERIAL AND METHODS: A single human premolar was fixed on a
typodont and prepared to receive crowns prepared by the CEREC CAD-CAM system.
Three fabrication techniques were used: digital scans using the CEREC Bluecam
scanner with titanium dioxide powder (TDP), digital scans using the CEREC Omnicam
scanner without TDP, and digital scans using the Omnicam scanner with TDP. Five
experimental groups (n=10) were designated: Bluecam (group B), Bluecam with
adjustments (group BA), Omnicam (group O), Omnicam with adjustments (group OA),
and Omnicam with TDP (group OP). The specimens were scanned using microcomputed
tomography to measure the vertical, horizontal, and internal fit and volumetric 3
dimensional (3D) internal fit values of each luting space. The paired t test was
used to evaluate mean marginal fit change after adjustments within the same
group. One-way analysis of variance and post hoc tests were used to compare
groups B, O, and OP (alpha=.05). RESULTS: Mean vertical fit values +/-standard
deviations of group B=29.5 +/-13.2 MUm; BA=26.9 +/-7.7 MUm; O=149.4 +/-64.4 MUm;
OA=49.4 +/-12.7 MUm; and OP=33.0 +/-8.3 MUm. Adjustments in the intaglio surface
and TDP application statistically influenced the vertical fit of group O
(P<.001). The percentage of vertical fit values <75 MUm in group B=89.3%,
BA=92.7%, O=31.0%, OA=73.5%, and OP=92.0%. Mean horizontal fit values for group
B=56.2 +/-21.5 MUm; 85.8 +/-44.4 MUm for group BA; 77.5 +/-11.8 MUm for group O;
102.5 +/-16.2 MUm for group OA; and 91.4 +/-19.4 MUm for group OP. Results from
group B were significantly different from those of the other test groups (P<.05).
The percentages of horizontal misfit were 61.2% in group B; 73.5% in group BA;
88.1% in group O; 92.4% in group OA; and 85.0% in group OP. Volumetric 3D
internal fit values in group B were 9.4 +/-1.3 mm3; 10.7 +/-1.0 mm3 in group BA;
11.8 +/-2.1 mm3 in group O; 11.0 +/-1.3 mm3 in group OA; and 9.6 +/-0.9 mm3 in
group OP. The overall results from groups B and OP were better than those of
group O, with regard to vertical misfit and volumetric 3D internal fit.
CONCLUSIONS: Different intraoral optical scanners, powder application, and
internal adjustments influenced the marginal discrepancy of crowns. Crowns
fabricated using the Omnicam system had significantly higher vertical discrepancy
and volumetric 3D internal fit than those fabricated using the Bluecam scanner
with TDP. Adjustments of the intaglio surface improved the vertical fit of crowns
made using the Omnicam scanner; however, TDP application before Omnicam scanning
improved the vertical fit as well as the volumetric 3D internal fit value of the
luting space of crowns.
PMID- 28689913
TI - A technique for immediately restoring single dental implants with a CAD-CAM
implant-supported crown milled from a poly(methyl methacrylate) block.
AB - This technique is used when a single dental implant is placed. A stent made of
autopolymerized acrylic resin was used to transfer the implant position to the
laboratory. Once the implant position was transferred, the stone cast was
scanned, and a computer-aided design and computer-aided manufacturing (CAD-CAM)
interim implant-supported crown was milled from a poly(methyl methacrylate)
(PMMA) block. A titanium insert, in contact with the implant platform and not the
PMMA material, was used to support the crown. The interim prosthesis was then
placed intraorally. The soft tissues were sutured, and the interim prosthesis was
left for a period of at least 3 months to confirm osseointegration and allow the
soft tissue to heal. A CAD-CAM titanium impression coping was made and used for
the definitive impression. The contours of the impression coping were identical
to the contours of the interim restoration. The data of the digital design of the
interim prosthesis were saved, and the definitive prosthesis was fabricated with
contours identical to those of the interim prosthesis.
PMID- 28689914
TI - Vertical repositioning accuracy of magnetic mounting systems on 4 articulator
models.
AB - STATEMENT OF PROBLEM: Research of the ability of a cast mounted on an articulator
on maintaining the identical position of a cast mounted on an articulator after
repeated repositioning is lacking, despite the possible effects this may have on
the occlusion of a mounted cast. PURPOSE: The purpose of this in vitro study was
to verify and compare the vertical repositioning accuracy of 4 different,
commercially available articulator magnetic mounting plate systems. MATERIAL AND
METHODS: Four articulators and their associated magnetic mounting plates were
selected for the study. These were the Artex AR articulator (Amann Girrbach AG),
the Denar Mark II articulator (Whip Mix Corp), the Kavo Protar Evo articulator
(Kavo Dental GmbH), and the SAM3 articulator (SAM Prazisionstechnik GmbH). Three
new magnetic mounting plates were prepared for each articulator system. The
repositioning accuracy of each mounting plate was evaluated by comparing the
standard deviation of the vertical distances measured between the mounting plate
and a laser displacement sensor. The lower arm of the articulator was secured,
and the vertical distance was measured by positioning the laser displacement
sensor positioned vertically above the mounting plate. Once the vertical distance
was measured, the mounting plate was detached from the articulator and reattached
manually to prepare for the next measurement. This procedure was repeated 30
times for each of the 3 magnetic mounting plates. Data were analyzed by ANOVA for
2-stage nested design and the Levene test (alpha=.05). RESULTS: Significant
differences were detected among articulator systems and between magnetic mounting
plates of the same type. The standard deviations of the measurements made with
the Artex AR articulator, Denar Mark II articulator, Kavo Protar Evo articulator,
and SAM3 articulator were 0.0027, 0.0308, 0.0214, and 0.0215 mm, respectively.
Thus, the repositioning accuracy could be ranked in the order as follows: Artex
AR, Kavo Protar Evo, SAM3, and Denar Mark II. CONCLUSIONS: The position of the
magnetic mounting plate after repositioning did not maintain an identical
position in the vertical dimension on any of the 4 articulator models tested. The
repositioning accuracy of the mounting plates showed significant differences
among the articulators tested in this study.
PMID- 28689915
TI - A 3-year clinical evaluation of endodontically treated posterior teeth restored
with two different materials using the CEREC AC chair-side system.
AB - STATEMENT OF PROBLEM: The introduction of polymer-infiltrated ceramic network
(PICN) materials may provide more options for dentists in restoring short
clinical crowns and extensively damaged posterior teeth, but clinical data for
their performance are lacking. PURPOSE: The purpose of this clinical study was to
compare the 3-year performance and survival rates of PICN material with those of
conservative ceramic onlay restorations for endodontically treated posterior
teeth using the CEREC AC chair-side system. MATERIAL AND METHODS: A total of 101
onlay restorations of endodontically treated posterior teeth using the CEREC AC
chair-side system were provided in 93 participants. The 101 teeth were divided
into 2 groups: Vita Enamic group and Vitablocs Mark II group. Using the modified
US Public Health Service quality evaluation system, 2 calibrated evaluators
examined the performance of the onlay restorations over 3 years. The Kaplan-Meier
method was adopted to analyze the survival rate of restorations (alpha=.05). The
log rank test was used to compare the survival rates of the 2 groups. The Fisher
exact test was performed to detect differences in the success rates for
extensively damaged teeth and short clinical crown restorations between the 2
groups. The Silness and Loe gingival index was also recorded. RESULTS: The
restoration survival rates in the 2 groups were 97.0% (Vita Enamic) and 90.7%
(Vitablocs Mark II) (P>.05). Five failures were recorded (4.95%). These failures
were caused by restoration debonding (60%), ceramic fractures (20%), and tooth
fractures (20%). There were no significant differences between the success rates
of restoring extensively damaged teeth and short clinical crowns between the 2
groups (P>.05). The periodontal condition of 25% of participants was improved 3
years after the onlay restorations. CONCLUSIONS: Onlay restorations of
endodontically treated posterior teeth with Vita Enamic using the CEREC AC chair
side system are clinically promising prosthodontic alternatives, with a survival
rate of 97.0% after 3 years. More research is needed to verify the results of
this study.
PMID- 28689916
TI - Molecular mechanism of anti-cancerous potential of Morin extracted from mulberry
in Hela cells.
AB - The flavonoids are of great interest due to their antioxidant and anti-cancerous
potential. The present study investigated the Morin extracted from mulberry
leaves and its anti-cancerous mechanism via cell inhibition, cell cycle analysis,
apoptosis, mRNA expression and antioxidant mechanism through reactive oxygen
species generation. Morin inhibited the proliferation of HeLa cells at IC50 of
214.28 MUM and led to morphological changes, followed by induction of cell cycle
arrest in G2/M-phase and ultimately resulted into apoptosis. Morin-induced G2/M
phase arrest was accompanied by the increase in mRNA expression of p53, p21 and
Wee 1 genes and decreased levels of CDK1, Cdc25c, Survivin, cyclin B1and CHK2.
Morin-induced apoptosis was regulated through multiple pathways, including
intrinsic and extrinsic pathway. The underlying mechanisms consisted of increased
mRNA expression of Bax, Bad, cytochrome c, Apaf-1, caspases-9, DR3, DR5, FasL,
FADD, caspases-10, PARP, PI3K, AKT, mTOR, P70S6K and Smac genes as well as
decreased expression of Bcl-2, Bcl-xL, AMPK, cIAP-1, cIAP-2, PKCepsilon and NF
kbeta. In addition, Morin treatment resulted in the generation of intracellular
ROS, which play an essential role in the induction of apoptosis. The present
study recommends the use of Morin in the development of functional foods with
anti-cancerous potential in the future.
PMID- 28689917
TI - Dioscin, a potent ITGA5 inhibitor, reduces the synthesis of collagen against
liver fibrosis: Insights from SILAC-based proteomics analysis.
AB - Inhibiting collagen generation is one effective method to treat liver fibrosis.
Dioscin showed protective effect against liver fibrosis in our previous studies,
and in the present work, SILAC-based proteomics was employed to test the
underlying mechanism. A total of 121 differentially expressed proteins caused by
dioscin in LX-2 cells were found, and dioscin significantly decreased the
expression levels of FN, FAK1, ITGA5, p-PI3K/PI3K, p-Akt/Akt, p-mTOR/mTOR,
Col1a1, Col1a2, Col2a1, Col5a1, Col6a1, and increased 2ABB level in vivo and in
vitro. Thus, we elucidated that dioscin specifically suppressed collagen
synthesis through modulating PI3K/Akt pathway. In addition, we found that dioscin
directly targeted with ITGA5 by molecular docking assay. SiRNA and overexpression
transfection tests showed that ITGA5 siRNA plus dioscin slightly altered the
effect of ITGA5 siRNA, and ITGA5 DNA transfection reversed the inhibitory effect
of dioscin on collagen expressions via PI3K/Akt pathway. Our data explicated that
dioscin should be considered as a novel and potent ITGA5 inhibitor to suppress
collagen synthesis, which can also be developed as an effective food and
healthcare product against hepatic fibrosis.
PMID- 28689918
TI - The effects of deoxyelephantopin on the cardiac delayed rectifier potassium
channel current (IKr) and human ether-a-go-go-related gene (hERG) expression.
AB - Elephantopus scaber Linn and its major bioactive component, deoxyelephantopin are
known for their medicinal properties and are often reported to have various
cytotoxic and antitumor activities. This plant is widely used as folk medicine
for a plethora of indications although its safety profile remains unknown. Human
ether-a-go-go-related gene (hERG) encodes the cardiac IKr current which is a
determinant of the duration of ventricular action potentials and QT interval. The
hERG potassium channel is an important antitarget in cardiotoxicity evaluation.
This study investigated the effects of deoxyelephantopin on the current, mRNA and
protein expression of hERG channel in hERG-transfected HEK293 cells. The hERG
tail currents following depolarization pulses were insignificantly affected by
deoxyelephantopin in the transfected cell line. Current reduction was less than
40% as compared with baseline at the highest concentration of 50 MUM. The results
were consistent with the molecular docking simulation and hERG surface protein
expression. Interestingly, it does not affect the hERG expression at both
transcriptional and translational level at most concentrations, although higher
concentration at 10 MUM caused protein accumulation. In conclusion,
deoxyelephantopin is unlikely a clinically significant hERG channel and Ikr
blocker.
PMID- 28689919
TI - Cytotoxic effects of gastrodin extracted from the rhizome of Gastrodia elata
Blume in glioblastoma cells, but not in normal astrocytes, via the induction of
oxidative stress-associated apoptosis that involved cell cycle arrest and p53
activation.
AB - Researches have been conducted to explore the biological effect of gastrodin, a
natural compound extracted from the rhizome of Gastrodia elata Blume, in
different models. However, the effects of gastrodin on cytotoxicity, cell cycle
distribution and oxidative stress in glia cells have not been explored. The aim
of this study was to investigate the cytotoxic effect of gastrodin and its
mechanisms in DBTRG-05MG human glioblastoma cells and CTX TNA2 rat astrocytes. In
DBTRG-05MG cells but not in CTX TNA2 cells, gastrodin (20-30 MUM) induced
cytotoxicity, G2/M phase cell cycle arrest and apoptosis. Regarding oxidative
stress, gastrodin (20-30 MUM) elevated intracellular ROS levels but reduced GSH
levels. Treatment with the antioxidant NAC (10 MUM) partially reversed gastrodin
altered antioxidant enzymes levels. Furthermore, gastrodin induced mitochondria
associated apoptosis. The apoptotic effects evoked by gastrodin were partially
inhibited by the antioxidant NAC and the pancaspase inhibitor Z-VAD-FMK.
Together, in DBTRG-05MG cells, but not in CTX TNA2 cells, gastrodin activated ROS
associated mitochondrial apoptotic pathways that involved cell cycle arrest.
These data provide insight into the molecular mechanisms governing the ability of
gastrodin to induce cytotoxicity in human glioblastoma cells and further suggest
that gastrodin is a new potential agent for the treatment of human gliblasoma.
PMID- 28689920
TI - Relationship between weight loss in obese knee osteoarthritis patients and serum
biomarkers of cartilage breakdown: secondary analyses of a randomised trial.
AB - OBJECTIVE: To explore effects of weight loss and maintenance on serum cartilage
biomarkers denaturation neoepitope for Collagen2 (Coll2-1) and Fibulin3 fragment
(Fib3-2), as well as correlations between Coll2-1 and Fib3-2 and symptomatic
improvement, in a knee osteoarthritis (KOA) population. DESIGN: 192 obese KOA
patients followed a 16 week weight loss intervention and 52 weeks weight
maintenance (ClinicalTrials.gov identifier: NCT00655941). Assessments were at 0,
8, 16 and 68 weeks. Serum Coll2-1 and Fib3-2 were determined with ELISA, and
symptoms by the Knee Osteoarthritis Outcome Score (KOOS) questionnaire. Changes
from week 0 and association between changes from baseline in body weight and
Coll2-1, Fib3-2, and the 5 KOOS domains were assessed at all time points.
RESULTS: Coll2-1 changes from baseline showed a decrease at week 8 (P = 0.0002),
no change at week 16 (P = 0.49), and an increase at week 68 (P = 0.036). Fib3-2
showed an increase from baseline at week 8 (P = 0.0015) and 16 (P < 0.0001), but
none at week 68 (P = 0.23). No statistically significant correlations were found
between changes in body weight and Coll2-1 and Fib3-2 at any time point (r <
0.05; P > 0.49). At all time-points there were significant positive correlations
between changes from baseline in Coll2-1 and in KOOSSports/Recreation (week 8,
16, 68: r = 0.17; P = 0.03; r = 0.16; P = 0.04; and r = 0.17; P = 0.04,
respectively). CONCLUSION: The clinical improvement after a substantial weight
loss and weight maintenance in KOA patients was not associated with decrease in
markers of cartilage breakdown Coll2-1 or Fib3-2, even with indications of a
slightly negative effect.
PMID- 28689921
TI - The novel mef(C)-mph(G) macrolide resistance genes are conveyed in the
environment on various vectors.
AB - BACKGROUND: The novel tandem genes mef(C) and mph(G) have been reported in marine
bacteria in Japan. This paper aimed to characterise the extent of environmental
distribution of mef(C) and mph(G) as well as their dissemination and persistence
in aquatic bacterial communities. METHODS: Erythromycin-resistant bacteria were
isolated from Japan, Taiwan and Thailand aquaculture sites. The mef(C)-mph(G)
genes were detected by PCR. The size of mobile genetic elements conveying mef(C)
and mph(G) was examined by Southern blotting. The conjugation rate was assessed
by filter mating. RESULTS: The mef(C)-mph(G) tandem genes were distributed in
erythromycin-resistant isolates from aquaculture seawater in Japan and northern
Taiwan and in animal farm wastewater in Thailand. A total of 29 bacterial
isolates were positive for mef(C)-mph(G). The genes were found on vectors of
various sizes. Partial sequencing of the traI relaxase gene revealed homology
with a pAQU1-like plasmid, an IncA/C-type plasmid and an SXT/R391 family
integrative conjugative element (SRI) as vectors. Thirteen isolates (45%) were
positive for traI(pAQU-IncA/C-SRI), whereas the others were negative. The
traI(pAQU-IncA/C-SRI)-positive isolates exhibited a higher transfer frequency (10
4-10-5 transconjugants/donor) than traI(pAQU-IncA/C-SRI)-negative isolates (<10
9). CONCLUSIONS: These results suggest that mef(C)-mph(G) are coded on various
vectors and are distributed among marine and wastewater bacteria in Asian
countries. Vectors with traI(pAQU-IncA/C-SRI) play a role in the spread of mef(C)
mph(G).
PMID- 28689922
TI - Detection of the colistin resistance gene mcr-1 in pathogenic Escherichia coli
from pigs affected by post-weaning diarrhoea in Italy.
AB - OBJECTIVES: The aim of this study was to investigate the presence of plasmid
mediated colistin resistance genes in Escherichia coli from pigs affected by post
weaning diarrhoea (PWD). METHODS: DNA samples collected from 51 E. coli isolates
from Italian pigs affected by PWD in 2015-2016 were studied. Isolates were
classified as presumptively resistant to colistin by routine susceptibility
testing and were investigated for the presence of the mcr-1 gene of plasmid
origin by PCR. E. coli isolates testing negative for mcr-1 were analysed for the
presence of a novel plasmid-mediated gene, mcr-2. Isolates were characterised for
fimbrial [F4 (k88), F5 (k99), F6 (987P), F18 and F41] and toxin (LT, STa, STb and
Stx2e) determinants by PCR as well as for the occurrence of haemolysis by
phenotypic observation. Susceptibility to apramycin, cefquinome, enrofloxacin,
florfenicol, gentamicin, tetracycline and trimethoprim/sulfamethoxazole (SXT) was
also determined by disk diffusion. RESULTS: Most of the isolates showed the
presence of at least one virulence factor, confirming their pathogenic potential.
The presence of mcr-1 was shown in 37 (72.5%) of the 51 isolates. All of the mcr
1-negative isolates tested negative for the mcr-2 gene. Moreover, 80.4% of the
isolates were resistant to apramycin, 9.8% to cefquinome, 54.9% to enrofloxacin,
52.9% to florfenicol, 76.5% to gentamicin, 96.1% to tetracycline and 78.4% to
SXT. CONCLUSIONS: This is the first report documenting the presence of the mcr-1
gene in pathogenic E. coli isolated from pigs affected by PWD in Italy.
PMID- 28689923
TI - In vitro activity of ceftolozane/tazobactam in combination with other classes of
antibacterial agents.
AB - OBJECTIVES: Combination antibiotic therapy has been used successfully to treat
some patients with bacterial infections. However, although certain combinations
may result in beneficial synergistic activity, others may produce antagonistic
effects resulting in poor treatment outcomes. Ceftolozane/tazobactam is an
antibacterial agent with potent activity against Pseudomonas aeruginosa and many
other Gram-negative pathogens, including extended-spectrum beta-lactamase (ESBL)
producing Enterobacteriaceae. This study aimed to evaluate potential synergistic
or antagonistic interactions between ceftolozane/tazobactam and a selection of
antibacterial agents. METHODS: Chequerboard analyses were conducted with
Escherichia coli, Klebsiella pneumoniae and P. aeruginosa isolates. RESULTS:
Combinations of ceftolozane/tazobactam with aztreonam, amikacin, tigecycline and
meropenem resulted in synergistic effects in some of the bacterial strains
tested. The potency of ceftolozane/tazobactam against common Gram-negative
pathogens was not compromised in the presence of other commonly prescribed
antibacterial agents, and ceftolozane/tazobactam did not antagonise the activity
of these other antibacterials. CONCLUSIONS: The synergy observed for some
antibacterial combinations in this study supplements the currently available
information for combination therapy and may suggest new directions for treating
challenging cases. Some synergistic effects may be attributed, at least in part,
to the ESBL-inhibitory activity of tazobactam, although this remains to be
proven. The mechanisms of the other synergistic interactions observed also
require further elucidation. Ceftolozane/tazobactam did not adversely affect the
activity of, and was not affected by, other antibacterial agents given
concurrently. In vivo studies will be needed to substantiate these results and to
determine their clinical relevance.
PMID- 28689924
TI - A national framework for an antimicrobial resistance surveillance system within
Iranian healthcare facilities: Towards a global surveillance system.
AB - OBJECTIVES: The threat of antimicrobial resistance (AMR) is growing rapidly,
perhaps more dramatically in developing countries. A demand to monitor, surveil
and predict AMR has prompted the design and implementation of AMR surveillance
systems (AMRSSs) at all geographic levels, especially in the national context.
This study reviewed AMRSSs in leading countries and organisations in order to
customise a comprehensive framework for a national system in Iran. METHODS: The
research was conducted in two phases: a review of the literature and comparative
analysis; and a knowledge, attitude and practice study. In the first phase, the
AMRSSs of pioneering organisations and countries were reviewed by examining
related documents. In the second phase, important components for the Iranian
national system were determined on the basis of the World Health Organization's
Global Antimicrobial Resistance Surveillance System (WHO GLASS). RESULTS: This
study determined the surveillance methods, priority specimens and pathogens,
testing methods, reporting protocols and scheduling, recommended data sets, and
tools and information flow necessary for the Iranian system. On this basis, a
national framework was developed using the class and activity diagrams in Unified
Modelling Language. A context diagram was also designed on the basis of a generic
biosurveillance architecture. CONCLUSIONS: The design and implementation of a
national AMRSS for Iranian healthcare facilities is critically required because
of irrational antimicrobial use in Iran and insufficient data regarding its
consequences.
PMID- 28689925
TI - A geographical workforce analysis of hand therapy services in relation to US
population characteristics.
AB - INTRODUCTION: A paucity of work force planning literature exists for hand therapy
services. PURPOSE: This descriptive study aimed to map the geographical
distribution of US Certified Hand Therapists (CHTs) and describe characteristics
of US populations living in respective CHT workplace Zip Code Tabulation Areas
(ZCTAs). METHODS: A de-identified Zip Code list of all active CHTs through April
2016 from the Hand Therapy Certification Commission, included 5572 CHTs with US
ZCTAs. The CHT ZCTAs were matched with population parameters "rurality",
"poverty" and "race and ethnicity" from the 2010 US Census and 2014 American
Community Survey. RESULTS: The 5,572 CHTs practice ZCTAs mostly overlapped with
high density US population areas, covering just 9% of the total number of 33,120
US ZCTAs. The population in CHT ZCTAs was 1) urban in nature, 2) with lower
poverty rates than ZCTAs without CHTs, and 3) mostly reflecting US race and
ethnicity population distribution. Only 3.7% of CHTs worked in large
concentrations of 11 to 26 CHTs per ZCTA near or in urban centers. Most CHTs,
67%, worked in one to three CHTs per ZCTA concentrations, contributing to a
larger geographic spread of CHT locations than expected. DISCUSSION AND
CONCLUSION: This study provides a foundational snap shot of the distribution, the
potential availability, of the 2016 CHT workforce in the context of US population
characteristics. It may serve as baseline for supply and demand studies and
interventions to grow the CHT profession and optimize the distribution of CHTs to
better meet population needs.
PMID- 28689927
TI - Tau mRNA 3'UTR-to-CDS ratio is increased in Alzheimer disease.
AB - Neurons frequently show an imbalance in expression of the 3' untranslated region
(3'UTR) relative to the coding DNA sequence (CDS) region of mature messenger RNAs
(mRNA). The ratio varies among different cells or parts of the brain. The Map2
protein levels per cell depend on the 3'UTR-to-CDS ratio rather than the total
mRNA amount, which suggests powerful regulation of protein expression by 3'UTR
sequences. Here we found that MAPT (the microtubule-associated protein tau gene)
3'UTR levels are particularly high with respect to other genes; indeed, the 3'UTR
to-CDS ratio of MAPT is balanced in healthy brain in mouse and human. The tau
protein accumulates in Alzheimer diseased brain. We nonetheless observed that the
levels of RNA encoding MAPT/tau were diminished in these patients' brains. To
explain this apparently contradictory result, we studied MAPT mRNA stoichiometry
in coding and non-coding regions, and found that the 3'UTR-to-CDS ratio was
higher in the hippocampus of Alzheimer disease patients, with higher tau protein
but lower total mRNA levels. Our data indicate that changes in the 3'UTR-to-CDS
ratio have a regulatory role in the disease. Future research should thus consider
not only mRNA levels, but also the ratios between coding and non-coding regions.
PMID- 28689928
TI - A survey of herbal weeds that are used to treat gastrointestinal disorders from
southern Thailand: Krabi and Songkhla provinces.
AB - ETHNOPHARMACOLOGICAL RELEVANCE: Weeds are plants grow naturally and are commonly
seen. They are mostly used for feedstuff. However, their use as herbs for
treating diseases, including gastrointestinal disorders, is rare. Therefore, the
present study aimed to: (1) quantify the number of herbal weeds used for treating
gastrointestinal disorders; (2) study local knowledge of weed utilization for
treating gastrointestinal disorders in Songkhla and Krabi provinces; and (3)
analyse quantitative data with the Informant Consensus Factor (ICF), Use Value
(UV) and Fidelity Level (FL). MATERIALS AND METHODS: The study was conducted from
November 2014 to January 2016 through semi-structured interviews with 35 folk
healers. The main questions were designed to obtain plant information, including
the local name, method of use, preparation method and medicinal properties. The
data were analysed by descriptive statistics, quantitative indexes (UV, ICF as
well as FL) and interpretation. RESULTS: A total of 49 species in 46 genera and
28 families were found. The most common use of weeds was as herbs (80%). The
preferred part used was the whole plant (76.27%). The preferred methods of drug
preparation and use were decoction and drink, respectively. The highest UV was
found for Acmella oleracea (0.83). The highest FLs (100%) were found for 12
species, including Amaranthus spinosus, Amaranthus viridis, Alternanthera
sessilis, Sauropus androgynus, Plantago major, and others. The highest ICF (0.93)
was found for treating toothache. CONCLUSION: Overall, there are reports on the
pharmacological activity of 31 species of weeds and reports on toxicity for 20
species of weeds. Therefore, awareness of the use of herbs is necessary to ensure
that they are used safely and that benefits arise from the therapy. This study
showed that medicinal weeds are still popularly used by folk healers. The
pharmacological properties were consistent with the local uses, which supported a
preliminary indication that the weed plants were effective for treating
gastrointestinal diseases.
PMID- 28689926
TI - Ablation of IB4 non-peptidergic afferents in the rat facet joint prevents injury
induced pain and thalamic hyperexcitability via supraspinal glutamate
transporters.
AB - The facet joint is a common source of neck pain, particularly after excessive
stretch of its capsular ligament. Peptidergic afferents have been shown to have
an important role in the development and maintenance of mechanical hyperalgesia,
dysregulated nociceptive signaling, and spinal hyperexcitability that develop
after mechanical injury to the facet joint. However, the role of non-peptidergic
isolectin-B4 (IB4) cells in mediating joint pain is unknown. Isolectin-B4 saporin
(IB4-SAP) was injected into the facet joint to ablate non-peptidergic cells, and
the facet joint later underwent a ligament stretch known to induce pain.
Behavioral sensitivity, thalamic glutamate transporter expression, and thalamic
hyperexcitability were evaluated up to and at day 7. Administering IB4-SAP prior
to a painful injury prevented the development of mechanical hyperalgesia that is
typically present. Intra-articular IB4-SAP also prevented the upregulation of the
glutamate transporters GLT-1 and EAAC1 in the ventral posterolateral nucleus of
the thalamus and reduced thalamic neuronal hyperexcitability at day 7. These
findings suggest that a painful facet injury induces changes extending to
supraspinal structures and that IB4-positive afferents in the facet joint may be
critical for the development and maintenance of sensitization in the thalamus
after a painful facet joint injury.
PMID- 28689929
TI - Serum C-reactive protein in patients undergoing elective shoulder arthroplasty.
Prospective study.
AB - BACKGROUND: The objective of the study was to determine the normalization curve
of the serum C-reactive protein (CRP) in elective shoulder arthroplasty. METHODS:
A prospective study including 58 consecutive patients who had undergone elective
shoulder arthroplasty. Forty-one patients had received a Reverse Shoulder
Arthroplasty, 13 a Total Shoulder Arthroplasty and 4 a Hemiarthroplasty. Based on
a pilot study, blood samples to determine CRP values were obtained at baseline (1
h before surgery), on the 1st, 2nd, 6th, 8th and 14th postoperative days. All the
patients included presented no postoperative complications during inpatient stay
or any re-admission during the three months after surgery. RESULTS: Mean CRP
values showed a rapid increase on the 1st postoperative day (7-fold higher than
the baseline in cuff tear arthropathy, 11-fold higher in primary osteoarthritis,
1-fold higher in acute fracture) and reached a peak on the 2nd postoperative day
(14-fold higher than the baseline in cuff tear arthropathy, 24-fold higher in
primary osteoarthritis and 2-fold higher in acute fracture). After the 2nd
postoperative day CRP values began to slowly decrease reaching the normal range
in the 14th postoperative day. CONCLUSIONS: Serum CRP levels after elective
shoulder arthroplasty rapidly increase to reach a maximum peak after the 2nd
surgery day and then slowly decrease to return to normality on the 14th day.
Knowing the normalization curve of CRP can be a helpful tool to help in the
diagnosis of acute infections in elective shoulder arthroplasty.
PMID- 28689930
TI - Long term verbal memory recall deficits in fragile X premutation females.
AB - Carriers of a FMR1 premutation allele (between 55 and 199 CGG repeats) are at
risk of developing a wide range of medical, psychiatric and cognitive disorders,
including executive dysfunction. These cognitive deficits are often less severe
for female premutation carriers compared to male premutation carriers, albeit
similar in nature. However, it remains unclear whether female premutation
carriers who exhibit executive dysfunction also report verbal learning and memory
deficits like those of their male counterparts. Here we employed the CVLT to
assess verbal learning and memory function in 19 female premutation carriers,
contrasting performance with 19 age- and IQ-matched controls. Group comparisons
revealed similar performance during the learning and short delay recall phases of
the CVLT. However, after a long delay period, female premutation carriers
remembered fewer words for both free and cued recall trials, but not during
recognition trials. These findings are consistent with reports for male
premutation carriers, and suggest that aspects of long term memory may be
adversely affect in a subgroup of premutation carriers with signs of executive
dysfunction.
PMID- 28689931
TI - Biphasic synovial sarcoma of the epiglottis: Case report and literature review.
AB - Synovial sarcomas are rare malignant tumors supposed to arise from pluripotent
mesenchymal stem cells predominantly affecting the deep soft tissue of the lower
and upper extremities in young adults. The occurrence of this tumor entity in the
head and neck is very uncommon and hence, timely diagnosis and treatment of
synovial sarcoma in this region remain a challenge. We describe the clinical and
molecular pathological features of a biphasic synovial sarcoma of the epiglottis,
a site where the primary manifestation of this tumor entity has not been
documented to date. With this background the existing literature is being
reviewed. Whilst wide excision of synovial sarcoma is considered as the primary
mainstay of therapy, (neo)adjuvant treatment strategies have been proposed to
increase local control and prolong disease-free survival.
PMID- 28689932
TI - Analysis of real-time crash risk for expressway ramps using traffic, geometric,
trip generation, and socio-demographic predictors.
AB - There have been numerous studies on real-time crash prediction seeking to link
real-time crash likelihood with traffic and environmental predictors.
Nevertheless, none has explored the impact of socio-demographic and trip
generation parameters on real-time crash risk. This study analyzed the real-time
crash risk for expressway ramps using traffic, geometric, socio-demographic, and
trip generation predictors. Two Bayesian logistic regression models were utilized
to identify crash precursors and their impact on ramp crash risk. Meanwhile, four
Support Vector Machines (SVM) were applied to predict crash occurrence. Bayesian
logistic regression models and SVMs commonly showed that the models with the
socio-demographic and trip generation variables outperform their counterparts
without those parameters. It indicates that the socio-demographic and trip
generation parameters have significant impact on the real-time crash risk. The
Bayesian logistic regression model results showed that the logarithm of vehicle
count, speed, and percentage of home-based-work production had positive impact on
crash risk. Meanwhile, off-ramps or non-diamond-ramps experienced higher crash
potential than on-ramps or diamond-ramps, respectively. Though the SVMs provided
good model performance, the SVM model with all variables (i.e., all traffic,
geometric, socio-demographic, and trip generation variables) had an overfitting
problem. Therefore, it is recommended to build SVM models based on significant
variables identified by other models, such as logistic regression.
PMID- 28689933
TI - Implications of advanced vehicle technologies for older drivers.
AB - Advances are being made in vehicle technologies that may help older adults
compensate for some of the declines in abilities associated with aging. These
advances hold promise for increasing vehicle safety, reducing injuries, and
making the driving task more comfortable. However, important research gaps remain
with regard to how various advanced technologies impact the safety of older
drivers, as well as older drivers' perceptions about these technologies. This
special issue contains seven original contributions that address these issues.
Specific topics include the: congruence of design guidelines with the needs and
abilities of older drivers, transfer of control between automated and manual
driving, use of in-vehicle monitoring technology, motivations for technology use
and assigned meanings, technology valuation, and effects on driving behavior.
PMID- 28689934
TI - Single-Center Comparison of Overall Survival and Toxicities in Patients with
Infiltrative Hepatocellular Carcinoma Treated with Yttrium-90 Radioembolization
or Drug-Eluting Embolic Transarterial Chemoembolization.
AB - PURPOSE: To compare overall survival and toxicities after yttrium-90 (90Y)
radioembolization and chemoembolization with drug-eluting embolics (DEE) in
patients with infiltrative hepatocellular carcinoma (HCC). MATERIALS AND METHODS:
Retrospective review of 50 patients with infiltrative HCC without main portal
vein invasion who were treated with 90Y radioembolization (n = 26) or DEE
chemoembolization (n = 24) between March 2007 and August 2012 was completed.
Infiltrative tumors were defined by cross-sectional imaging as masses that lacked
well-demarcated boundaries, and treatment allocations were made by a
multidisciplinary tumor board. Median age was 63 years; median tumor diameter was
9.0 cm; and there were no significant differences between groups in performance
status, severity of liver disease, or HCC stage. Toxicities were graded by Common
Terminology Criteria for Adverse Events v4.03. Overall survival from treatment
was assessed by Kaplan-Meier analysis, with analysis of potential predictors of
survival with log-rank test. RESULTS: There was no difference in the average
number of procedures performed in each treatment group (DEE, 1.5 +/- 1.1; 90Y,
1.6 +/- 0.5; P = .97), and technical success was achieved in all cases. Abdominal
pain (73% vs 33%; P = .004) and fever (38% vs 8%; P = .01) were more frequent
after DEE chemoembolization. There was no significant difference in median
overall survival between treatment groups after treatment (DEE, 9.9 months; 90Y,
8.1 months; P = .11). CONCLUSIONS: 90Y radioembolization and DEE
chemoembolization provided similar overall survival in the treatment of
infiltrative HCC without main portal vein invasion. Abdominal pain and fever were
more frequent after DEE chemoembolization.
PMID- 28689935
TI - Percutaneous Coil Embolization for the Treatment of a Giant Brachial Artery
Pseudoaneurym in a Child.
AB - Brachial artery pseudoaneurysm is a rare phenomenon. When a diagnosis of brachial
artery pseudoaneurysm is established, early and appropriate treatment should be
performed as soon as possible to prevent possible complications, such as
hemorrhage, rupture, and upper limb and finger losses. Open surgical repair is
usually the cornerstone of treatment; however, we here report a case of giant
brachial pseudoaneurysm in a 2-year-old girl, which was successfully treated with
percutaneous coil embolization.
PMID- 28689936
TI - Results of One-Stage or Staged Amputations of Lower Limbs Consequent to Critical
Limb Ischemia and Infection.
AB - BACKGROUND: Amputations of lower limbs can be conducted as one-stage amputation
(OSA) or staged amputation (SA) procedures. The objective of this study was to
analyze technical success and mortality rates of both techniques, as well as
factors that might influence outcomes in patients with critical limb ischemia
(CLI). METHODS: A retrospective study of 185 consecutive patients with CLI who
underwent amputations in the period 2004-2011. Primary end points were rates of
technical success (healing without dehiscence or reintervention) and mortality.
The influence on outcomes of demographic data, clinical status, and comorbidities
was also analyzed by logistic regression. RESULTS: A total of 101 SA (91
patients) and 106 OSA (94 patients) were analyzed. SA had proportionally higher
success rate (SA 77.2% vs. OSA 66.0%, P = 0.0253), lower perioperative mortality
rate (SA, 10.9% vs. OSA, 20.7%, P = 0.0247), and lower 30-day mortality rate (SA,
12.2% vs. OSA, 23.8%, P = 0.0220) in spite of more cases with Rutherford classes
5 and 6 (SA, 87.1% vs. OSA, 72.6%, P = 0.0047), diabetes (71.2% vs. 55.6%, P =
0.0076), and infection (44.5% vs. 28.3%, P = 0.0061). Logistic regression
demonstrated that in SA, success was more frequent in patients with diabetes who
did not use insulin (P = 0.0072), in those with transfemoral amputations (P =
0.0392), with no coronary artery disease (P = 0.0053), and in foot infection (P =
0.0446), while for OSA success was more frequent in nondiabetic patients (P =
0.0077), limbs without infection (P = 0.0298), amputations at foot level (P =
0.0155), or transfemoral amputations (P = 0.0030). CONCLUSIONS: SA had a higher
rate of technical success and lower mortality rates than OSA, even with greater
number of patients with diabetes and more severe cases of ischemia and infection.
However, prospective studies comparing both techniques are needed for further
evidence.
PMID- 28689937
TI - Multiple Spontaneous Iliac and Femoral Arteriovenous Fistulas.
AB - An arteriovenous fistula (AVF) in a limb involves an abnormal connection between
a limb artery and vein. It can be due to trauma or iatrogenic injury. Traumatic
AVFs can be caused by penetrating or gunshot injuries to the limb, whereas
iatrogenic causes include catheter intervention to the groins or open surgery of
the inguinal space. By contrast, the occurrence of multiple spontaneous AVFs is
rare. We report a case of endovascular therapy for multiple spontaneous AVFs
between the iliac artery and the vein, common femoral artery and the vein,
superficial artery and the saphenous vein, and deep femoral artery and the vein.
PMID- 28689938
TI - Gonadal Vein Transposition in Nutcracker Syndrome.
AB - BACKGROUND: Nutcracker syndrome, caused by mesoaortic compression of the left
renal vein leading to symptoms related to venous hypertension, is an uncommon
entity that may require operative intervention. Traditional open transposition of
the left renal vein to the vena cava has been shown to have a reintervention rate
of up to 30%, while also having additional morbidity associated with laparotomy.
More recently, endovascular stenting has been described in several small series
but have reported stent fracture, thrombosis, and migration. METHODS: We report
the case of a 26-year-old woman with 4 months of intermittent flank pain and
hematuria, diagnosed with nutcracker syndrome by both duplex ultrasound and axial
based imaging. RESULTS: The patient underwent catheter venography confirming left
renal vein compression, which also demonstrated a dilated gonadal vein measuring
11 mm leading to significant pelvic varices. Through a left lower quadrant
retroperitoneal exposure, the gonadal vein was transposed to the left common
iliac vein with completion venography demonstrating relief of renal venous
congestion. The patient was discharged uneventfully with immediate resolution of
symptoms and remains symptom-free at 6-month follow-up. CONCLUSIONS: Gonadal vein
transposition is an effective alternative surgical treatment for nutcracker
syndrome.
PMID- 28689939
TI - Variation in Transfusion Practices and the Association with Perioperative Adverse
Events in Patients Undergoing Open Abdominal Aortic Aneurysm Repair and Lower
Extremity Arterial Bypass in the Vascular Quality Initiative.
AB - BACKGROUND: Blood transfusions are associated with adverse events. We examined
perioperative transfusion practices and associated complications following open
vascular procedures nationwide in the Vascular Quality Initiative (VQI). METHODS:
Adults undergoing open abdominal aortic aneurysm repair (OAR) and lower extremity
arterial bypass (Bypass) within VQI (2003-2016) were identified. All emergent
cases, patients with preoperative hemoglobin <7 g/dL, preoperative
hospitalization >1 day, or a return to operating room during the index
hospitalization were excluded. Units of red blood cells transfused were the
primary outcome. Secondary outcomes were postoperative myocardial infarction (MI)
and death. Patient, center, and procedural factors were evaluated. Multivariable
mixed effects negative binomial regression and multivariable logistic regression
were performed. RESULTS: We identified 24,131 procedures (OAR 3885, 16.1%; Bypass
20,246, 83.9%) among 22,532 patients (10.1% had >1 procedure). Overall, 37.5% of
OAR and 19.5% of Bypass were transfused. Transfusion rates varied across
estimated blood loss quartiles and across various preoperative hemoglobin levels.
The overall rate of postoperative MI and death was 4.0% and 1.8% for OAR, and
2.2% and 0.7% for Bypass, respectively. In univariate and multivariable analysis,
transfusions were associated with an increased risk of postoperative MI and
death. A mixed effects negative binomial model demonstrated variation in
transfusions across centers (P < 0.001). Female gender and preoperative anemia
were significantly associated with transfusions. CONCLUSIONS: Blood transfusions
are variable across centers in VQI. Transfusions are associated with a higher
postoperative MI and death after OAR and Bypass. Efforts to reduce transfusion
may focus on center variability, gender, and preoperative anemia.
PMID- 28689940
TI - Carotid Body Tumor Resection: Just as Safe without Preoperative Embolization.
AB - BACKGROUND: Carotid body tumors (CBTs) are rare entities for which surgical
resection remains the gold standard. Given their hypervascularity, preoperative
embolization is often used; however, controversy exists over whether a benefit is
associated. Proponents of embolization argue that it minimizes blood loss and
complications. Critics argue that cost and stroke outweigh benefits. This study
aimed to investigate the impact of embolization on outcomes following CBT
resection. METHODS: Patients undergoing CBT resection were identified using the
Healthcare Cost and Utilization Project State Inpatient Database for 5 states
between 2006 and 2013. Patients were divided into 2 groups: carotid body tumor
resection alone (CBTR) and carotid body tumor resection with preoperative
arterial embolization (CBETR). Descriptive statistics were calculated using
arithmetic means with standard deviations for continuous variables and
proportions for categorical variables. Patients were propensity score matched on
the basis of sex, age, race, insurance, and comorbidity prior to analysis. Risk
adjusted odds of mortality, stroke, nerve injury, blood loss, and length of stay
(LOS) were calculated using mixed-effects regression models with fixed effects
for age, race, sex, and comorbidities. RESULTS: A total of 547 patients were
identified. Of these, 472 patients underwent CBTR and 75 underwent CBETR. Mean
age was 54.7 +/- 16 years. Mean number of days between embolization and resection
was 0.65 +/- 0.72 days (range 0-3). When compared with CBTR, there were no
significant differences in mortality for CBETR (1.35% vs. 0%, P = 0.316), cranial
nerve injury (2.7% vs. 0%, P = 0.48), and blood loss (2.7% vs. 6.8%, P = 0.245).
Following risk adjustment, CBETR increased the odds of prolonged LOS (odds ratio
5.3, 95% confidence interval 2.1-13.3). CONCLUSIONS: CBT resection is a
relatively rare procedure. The utility of preoperative tumor embolization has
been questioned. This study demonstrates no benefit of preoperative tumor
embolization.
PMID- 28689941
TI - Endotension after Abdominal Aortic Aneurysm Endovascular Repair in Cirrhotic
Patients.
AB - BACKGROUND: Endotension can present a real challenge for the long-term success of
endovascular aortic repair (EVAR). Sometimes, it can be associated with liver
dysfunction and consequent plasmatic alterations as in the 2 cases reported here.
METHODS: Significant and progressive abdominal aortic aneurysms (AAA) sac
enlargement, without radiologic signs of endoleak, was observed in 2 patients
during a 3-year follow-up after EVAR. The first was a 70-year-old man affected by
viral liver cirrhosis and the second was a 71-year-old man with cirrhosis due to
alcoholic liver disease. RESULTS: Both patients underwent successful conversion
to open AAA repair; intraoperative findings confirmed the diagnosis of
endotension. CONCLUSIONS: Cirrhosis-induced plasmatic alterations may affect long
term efficacy of EVAR and should be considered when weighing endovascular
treatment against open AAA repair in these high-risk patients. Surgical
conversion is feasible despite the high procedural risk associated with liver
disease.
PMID- 28689942
TI - Life Expectancy and Outcome of Different Treatment Strategies for Critical Limb
Ischemia in the Elderly Patients.
AB - BACKGROUND: The treatment of critical limb ischemia (CLI) in the elderly patients
is challenging because of the comorbidity and fragility of these patients. We
analyzed survival in relation to different treatment options and estimated life
expectancy of our study group by age and gender. METHODS: All patients aged >=70
years, presenting with chronic CLI, between 2006 and 2013 were included. The
treatment was conservative, endovascular, surgical, or by primary major
amputation. The interest was in the effect of conservative versus nonconservative
treatment on survival. Furthermore, we compared mortality and life expectancy
between the study population to the overall Dutch population by age and gender.
RESULTS: In total, 686 legs in 651 patients were treated. Initial treatment of
patients was conservative (n = 181), endovascular (n = 259), surgical (n = 169),
or amputation (n = 42). The overall 1-year mortality was 29%. Patients were
stratified by age: 70-79 (n = 350) years and >=80 (n = 301) years. Higher
mortality rate ratios (RR) were found in octogenarians compared with patients
aged 70-79 years, in the endovascular (P < 0.001) and surgical (P < 0.001) group.
The mortality RRs of conservative relatively to nonconservative treatment was
0.84 (95% confidence interval: 0.65-1.09; P = 0.19), not significantly differing
between both age groups (P = 0.74). The mortality RR of 3.72 of our study
population to the Dutch general population was high, with an excess mortality of
272%. Life expectancy at the age of 70 years was substantially decreased by 9 and
8 years for, respectively, the male and female population. CONCLUSIONS: Mortality
rates in elderly patients with CLI are high, corresponding with a decreased life
expectancy, regardless of the type of intervention. Revascularization is
associated with high periprocedural mortality, especially in octogenarians.
Conservative treatment is noninferior to nonconservative treatment in terms of
mortality and should be considered as the treatment in octogenarians with
substantial comorbidity.
PMID- 28689943
TI - Real-Life Experience with Ovation Stent Graft: Lesson Learned from the First One
Hundred Fifty Treated Patients.
AB - BACKGROUND: The objective of the study was to report immediate and midterm
results of an unselected population of patients treated for abdominal aortic
aneurysms (AAAs) by endovascular aneurysm repair (EVAR) using the Ovation stent
graft. METHODS: A double-center retrospective study was conducted on a
prospectively collected database between 2012 and 2015. One hundred fifty-six
elective patients were included. The outcome measures considered for analysis
were primary technical success, 30-day and midterm reinterventions, and all-cause
and AAA-related mortality rates. The presence of an aortic neck <=10 mm, and of a
noncylindrical aortic neck, as well as a narrowed aortic bifurcation was defined
as an aortic bifurcation average diameter (ABaverage) <= 18 mm or an ABarea <= 20
mm2, and an external iliac artery diameter <=5 mm was considered as independent
factors potentially influencing the outcome. RESULTS: Male patients totaled 128
(82.1%), and mean age was 74.83 +/- 6.76 years (range: 56-91). Mean aortic
diameter was 57.15 +/- 8.77 mm, mean diameter at inferior renal artery level + 13
was 24.44 +/- 3.31 mm, and mean aortic neck length was 18.77 +/- 8.45 mm. Fifty
four patients (34.6%) had an aortic neck <=10 mm, and cylindrical aortic neck
shape was present in 34 patients (21.8%). Regarding the aortic bifurcation (AB),
31 patients (19.9%) presented ABaverage <= 18 mm, and 35 (22.4%) an ABarea <= 20
mm2. Technical success was achieved in all cases. At 30-day follow-up, 2 type I
endoleaks (1.3%) were detected. One patient was successfully treated
endovascularly by proximal aortic cuff implantation, while the other patient
refused further treatment. Three-month unscheduled computed tomographic
angiography shows endoleak resolution and complete aneurysm seal. One patient
suffered from a limb graft occlusion, managed by medical treatment. At a mean
follow-up time of 20.4 +/- 8.8 (1-60) months, 6 reinterventions were reported,
including 2 embolizations for type II endoleak and 4 for iliac and femoral vessel
occlusive disease. Log-rank test on preoperative anatomical features showed no
significant differences in terms of freedom from reinterventions, and P values
were 0.653 for aortic neck length <=10 mm, 0.309 for noncylindrical aortic neck
length shape, 0.520 for ABaverage <= 18 mm, 0.604 for ABarea <= 20 mm2, and 0.421
for external iliac artery diameter <=5 mm. CONCLUSIONS: Our initial experience
suggests that in an unselected patient population undergoing AAA repair, EVAR by
Ovation stent graft can be performed safely with satisfactory immediate and
midterm outcomes.
PMID- 28689944
TI - Popliteal Venous Aneurysm and Multiple Lower Extremity Varicose Veins Presenting
with a Left-Sided Inferior Vena Cava.
AB - A venous aneurysm is a relatively rare disease defined by cystic vasodilated
lesions in a general vein. Popliteal venous aneurysm (PVA) is a rare clinical
entity, and the first signs may be a thromboembolic event. They can cause
potentially life-threatening diseases, such as pulmonary embolism and deep venous
thrombosis. A left-sided inferior vena cava (IVC) is a common anomaly associated
with venous thrombus, resulting in anatomical variations in the venous return
from the lower limbs. The general vascular malformation of PVA and left-sided IVC
should also be preoperatively understood because of the unpredictable risk of
thromboembolic complications.
PMID- 28689945
TI - Chimney Stent-Graft Repair for Concurrent Inferior Mesenteric Artery Aneurysm and
Infrarenal Abdominal Aortic Aneurysm: Case Report.
AB - PURPOSE: To report a rare case of concurrent inferior mesenteric artery (IMA)
aneurysm and infrarenal abdominal aortic aneurysm (AAA) with a novel indication
for the use of chimney stent-graft technique in this patient. CASE REPORT: An 82
year-old man with an asymptomatic 4.4-cm fusiform AAA and 3.6-cm IMA aneurysm,
coupled with chronic occlusion of celiac artery and superior mesenteric artery at
the ostia, underwent endovascular repair of both aneurysms. Preservation of the
IMA and treatment of both aneurysms were achieved with IMA aneurysm stenting,
aortic aneurysm stenting and IMA chimney stenting. At 1, 6, and 12 months
surveillance, the grafts remained patent without endoleak. CONCLUSIONS: The IMA
chimney with aortic stenting technique may be safely used in patients who require
preservation of the IMA during AAA and IMA aneurysm repairs.
PMID- 28689946
TI - Evaluating the Effectiveness of Internal Iliac Artery Branched Endovascular Stent
Grafts.
AB - BACKGROUND: The aim of this study is to describe our institutional experience
using iliac branch grafts (IBGs) in aortoiliac aneurysm repair. METHODS: From
October 2009 to April 2016, 41 consecutive patients (all men), mean age 71.7
years (range 55-87), underwent IBG implantation. Abdominal aortic aneurysm with
common iliac artery involvement (n = 21) or bilateral common iliac artery
aneurysms (n = 20) were indications. Computed tomography was used to evaluate
patency and postoperative endoleaks within 1 month of implantation and after 1
year. RESULTS: A total of 42 IBGs were deployed in 41 patients successfully. One
hundred percent of grafts implanted were patent at 1 month and at annual follow
up. There was 1 mortality at 30 days, due to acute renal failure. Sixteen type II
and 1 type Ib endoleaks were found, for which 3 reinterventions were performed
and the remainder treated conservatively. Five patients had complications which
required reintervention. CONCLUSIONS: IBG placement has excellent short-term
outcomes and potential to limit buttock claudication in the treatment of
abdominal aortic aneurysms involving the iliac arteries.
PMID- 28689947
TI - A Novel Iliac Morphology Score Predicts Procedural Mortality and Major Vascular
Complications in Transfemoral Aortic Valve Replacement.
AB - BACKGROUND: Vascular complications remain a significant technical challenge for
transfemoral TAVR (transcatheter aortic valve replacement). The goal of this
study is to develop a preoperative tool for prediction of major vascular
complications of TAVR. METHODS: A retrospective review was performed of all
patients who underwent transfemoral TAVR at a tertiary medical center from 2011
to 2015. Iliofemoral arterial measurements were obtained with computed tomography
angiography three-dimensional reconstruction images and an Iliac Morphology Score
(IMS) was created from these measurements. Vascular complications were defined by
Valve Academic Research Consortium (VARC-2) criteria. Statistical analyses were
performed utilizing chi-squared test, Student's t-test, and binomial regression.
RESULTS: We analyzed the data of 198 transfemoral TAVR patients. VARC-2 vascular
complications were seen in 25 patients (13%). Major and minor vascular
complication rates in the entire cohort were 4% (n = 7) and 9% (n = 18),
respectively. Thirty-one patients (15.6%) required vascular surgery consultation.
A total of 24 patients (12%) required surgical or percutaneous vascular
interventions. Univariate analysis identified gender, iliac diameter, iliac
calcification, and access type (open versus percutaneous) as predictors of major
complications. The IMS was composed of ipsilateral minimum iliac diameter and
iliac calcifications based on area under the receiver operator curve (AUROC)
analysis (P < 0.05, AUROC = 0.82). Arterial size and calcification were
classified with a value of 0-3 based on severity. Multivariate analysis
identified gender and IMS as independent predictors of major complications. The
mean IMS for the cohort was 3.4 (range 0-6). Patients were divided into high (IMS
>= 5, n = 55) and low risk (IMS<5, n = 143) groups based on the inflection point
for specificity (73%) and sensitivity (83%). The high-risk group had smaller
iliac diameters, areas, luminal volumes, and a higher rate of major vascular
complications (9% vs. 1%, P = 0.001). The 30-day mortality rate in the high score
group was 9% and 1.4% in low score group (P = 0.02, AUROC = 0.72). CONCLUSIONS:
An IMS composed of ipsilateral minimum iliac diameter plus iliac calcification is
an excellent predictor of major vascular complications and mortality. Alternative
access in patients with high IMS may reduce major vascular complications and 30
day mortality.
PMID- 28689948
TI - Endovascular Treatment of Penetrating Injury to the Vertebral Artery by a Stab
Wound: Case Report and Literature Review.
AB - BACKGROUND: We describe a unique case of a patient with penetration of the
cervical region by a stab wound, who required emergency care for the controlled
removal of the knife and for vertebral artery trauma (VAT) treatment. Although
rare, VAT causes high morbidity and mortality. METHODS: A patient admitted for
emergency care was diagnosed with traumatic complete section of the vertebral
artery by a knife and underwent removal of the knife under radioscopic
supervision and vertebral artery embolization with coils. RESULTS: The knife was
removed successfully, the bleeding was controlled, and the patient did not
present any sequelae. CONCLUSIONS: In the authors' experience, a patient in an
emergent state due to VAT can be treated effectively and quickly with proximal
embolization.
PMID- 28689949
TI - Three Extremely Rare Findings in the Same Patient: Harlequin Syndrome,
Thyrocervical Trunk Aneurysm, and Systemic-Pulmonary Arterio-Arterial Fistula.
AB - Harlequin syndrome is a rare autonomic disorder characterized by unilateral
diminished sweating and flushing of the face in response to heat or exercise.
Extrinsic ganglion compressions, most of the times by neoplasms, can induce the
syndrome. During investigation of a 27-year-old woman presenting Harlequin
syndrome with diminished sweating on the left side and flushing of the right half
of her face, a left thyrocervical trunk aneurysm was detected by angio-magnetic
resonance imaging. Thyrocervical trunk aneurysms are rare, and only a few cases
have been reported. Treatment is advised due to possible rupture and airway
compression by the resulting hematoma. Endovascular treatment was scheduled.
Angiographies revealed bronchial arteries arising from a common trunk at the
right thyrocervical trunk and the left bronchial artery was feeding an arterio
arterial fistula to the left pulmonary artery; the left thyrocervical trunk
aneurysm was confirmed and an anomalous artery arising from the aneurysm
converged to the left pulmonary artery arterio-arterial fistula; the fistula was
also supplied by a branch of the left internal mammary artery. The young age and
lack of clinical antecedents suggest a congenital etiology for this fistula. The
treatment was postponed until cardiopulmonary repercussions of the arterio
arterial fistula could be assessed. Coil embolization of the aneurysm was
performed in a second procedure. The fistula was not treated. The patient has
been followed up for 12 months without complications.
PMID- 28689951
TI - Spot Stenting of Supra-aortic Branch Vessels for Residual Type A Dissection.
AB - The purpose of this report was to describe the exclusion of the false lumen in a
residual type A aortic dissection (TAAD) by the deployment of 2 covered stents:
one in the right common carotid artery (RCCA) and one in the left subclavian
artery (LSA). A 77-year-old female, already treated with ascending aorta
replacement for acute TAAD, was referred to our center for a 97-mm post
dissection arch aneurysm. A computed tomography angiography (CTA) showed false
lumen patency by reperfusion from secondary tears located at the level of RCCA
and LSA. No primary aortic tear was noted. Under local anesthesia and by
transfemoral percutaneous approach, the tears at the level of RCCA and LSA were
covered by a 9-mm Viabahn stent graft (Gore, Flagstaff, AZ), and a 10-mm V-12
stent graft (Maquet, Rastatt, Germany), respectively. The false lumen was finally
occluded by the deployment of a 6-mm vascular plug at the level of LSA re-entry
tear, by left transbrachial puncture. The procedure was completed uneventfully.
Twelve-month CTA showed exclusion of the false lumen, patency of all supra aortic
trunks, and initial shrinkage of the aneurysm. Spot stenting of secondary re
entry tears, already described for visceral branches, seems to be safe and
effective also for supra-aortic trunks in selected patients.
PMID- 28689950
TI - An Accumulated Deficits Model Predicts Perioperative and Long-term Adverse Events
after Carotid Endarterectomy.
AB - BACKGROUND: There is increasing recognition that decreased reserve in multiple
organ systems, known as accumulated deficits (AD), may better stratify
perioperative risk than traditional risk indices. We hypothesized that an AD
model would predict both perioperative adverse events and long-term survival
after carotid endarterectomy (CEA), particularly important in asymptomatic
patients. METHODS: Consecutive patients undergoing CEA between 1st January 2000
and 31st December 2010 were retrospectively identified. Seven of the deficit
items from the Canadian Study of Health and Aging-frailty index (coronary
disease, renal insufficiency, pulmonary disease, peripheral vascular disease,
heart failure, hypertension, and diabetes) were tabulated for each patient.
Predictors of perioperative and long-term outcomes were evaluated using
regression analysis. RESULTS: About 1,782 CEAs in 1,496 patients (mean age: 71.3
+/- 9.3 years, 56.3% male, 35.4% symptomatic) were included. The risk of major
adverse events (stroke, death, or myocardial infarction) at 30 days for patients
with <=3 deficits was 2.53% vs. 8.81% for patients with >=4 deficits (P < 0.001).
For patients with >=5 deficits, the risk was 15.18%. Each additional deficit
increased the odds of a 30-day major adverse event and hospital stay >2 days by
1.64 (P < 0.001) and 1.15 (P < 0.001), respectively. In multivariate analysis,
the presence of >=4 deficits was more predictive of perioperative major adverse
events (odds ratio [OR] = 3.62, P < 0.001) than symptomatology within 6 months
(OR = 1.57, P = 0.08) or octogenarian status (OR = 2.00, P = 0.02). Kaplan-Meier
analysis showed significantly decreased survival over time with accumulating
deficits (P < 0.001). Patients with >=4 deficits have a hazards ratio for death
of 2.6 compared to patients with <=3 deficits (P < 0.001). Overall survival is
estimated at 79.5% (95% confidence interval [CI]: 0.77-0.82) at 5 years in
patients with <=3 deficits versus 52.4% (95% CI: 0.46-0.58) in patients with >=4
deficits, respectively. In subgroup analysis of asymptomatic patients, 5-year
survival for octogenarian male patients with >=4 deficits was only 26.8%. For
asymptomatic males aged 70-79 years with >=4 deficits, 5-year survival was 59.9%.
CONCLUSIONS: An AD model is more predictive of perioperative adverse events after
CEA than age or symptomatic status. This model remains predictive of long-term
survival. In asymptomatic male octogenarians with 4 or more AD, 5-year survival
is severely limited.
PMID- 28689952
TI - A Novel Off-the-Shelf Technique for Endovascular Repair of Type III and IV
Thoracoabdominal Aortic Aneurysms Using the Gore Excluder and Viabahn Branches.
AB - BACKGROUND: The aim of this study is to describe the use of a novel off-the-shelf
technique to repair type III and type IV thoracoabdominal aortic aneurysms
(TAAAs) in the absence of available prefabricated branched devices. METHODS: All
patients undergoing endovascular repair of type III and IV TAAAs using this
technique were included from a prospectively maintained registry at a regional
aortic referral center. The proximal bifurcated Gore C3 Excluder device is
positioned in the descending thoracic aorta with the contralateral gate 2-3 cm
above the celiac artery. From an axillary approach, the contralateral gate
renovisceral branches are sequentially cannulated and simultaneously stented
using Viabahn covered stents. In cases were the celiac artery could not be
excluded, a parallel stent (snorkel) was added adjacent to the proximal
endograft. All branches are simultaneously balloon dilated to ensure proximal
gutter seal in the contralateral gate. Via the ipsilateral limb, the device can
then be extended with a flared iliac extension and/or additional bifurcated
device to obtain seal in the distal aorta (previous open repair) or common iliac
arteries. RESULTS: Eight patients (male = 6, mean 78 years of age) were treated
in this manner since January 2015. All patients underwent repair using Gore C3
device with 3 (n = 5) or 4 (n = 3) renovisceral branches. The celiac artery was
sacrificed in 4 patients and 1 renal artery in 1 patient. Mean fluoroscopy time
was 88.7 min with a mean of 92.3 cc contrast utilized. Median length of stay was
7 days with 3 days spent in the intensive care unit. No major cardiac,
respiratory, renal, neurologic, or wound complications occurred. Three patients
had early endoleaks treated with additional endovascular techniques (n = 2) or
open surgical ligation (n = 1) during the index hospitalization. Two late
endoleaks were identified; 1 type II with stable sac size and 1 type III
requiring iliac limb relining. All limbs and branches remain patent at the time
of the last imaging study (mean 6.8 months). CONCLUSIONS: We present an
endovascular technique for repair of type III and IV TAAAs which appears to be
both feasible and safe with good short-term outcomes.
PMID- 28689953
TI - The Significance of the Angle between Superior Mesenteric Artery and Aorta in
Spontaneous Isolated Superior Mesenteric Artery Dissection.
AB - BACKGROUND: The aim of this study is to assess the significance of the angle
between superior mesenteric artery (SMA) and distal aorta in spontaneous isolated
superior mesenteric artery dissection (SISMAD) by clinical and biomechanical
analyses. METHODS: Thirty-seven patients with SISMAD (1 asymptomatic) and 148
controls (1:4 matched for age [mean 50.2 years], gender [92% male], and body mass
index, and being ruled out for arterial disease) underwent aortic computed
tomography angiography. SMA-distal aorta angle, measured on sagittal plane, was
compared along with baseline characteristics (body mass index, smoking history,
and comorbidities) between groups, and assessed as tool to evaluate SISMAD risk
after stratification into 4 angle-interval categories. Flow analysis and fluid
structure interaction study were conducted based on patient-specific models with
ultrasound-measured boundary conditions to further reveal the flow pattern and
loading distribution in the 4 angle-interval categories. RESULTS: SISMAD patients
versus controls had larger mean SMA-distal aorta angle (73 +/- 19.8 degrees vs.
50 +/- 18.81 degrees , P < 0.001), and more frequently smoking history (62% vs.
40%, P = 0.02) and hypertension (59% vs. 34%, P < 0.001), all multivariate
predictors of no SISMAD (odds ratio 0.946 [95% confidence interval 0.927-0.966];
0.415 [0.198-0.87]; and 0.252 [0.117-0.544], respectively). Odds ratio for SISMAD
increased with increasing SMA-distal aorta angle (1, 10, 57, and 73 for <50
degrees , 50-69 degrees , 70-90 degrees , and >90 degrees , respectively; P <
0.05 for >70 degrees ). In silico study confirmed that larger angle is associated
with higher stress in the arterial wall and higher oscillatory shear index in the
vessel lumen at the SMA superior convex, where dissection commonly occurs.
CONCLUSIONS: Besides smoking history and hypertension, SISMAD was positively
associated with a morphological parameter, the SMA-distal aorta angle. This might
be due to the greater wall stress and oscillatory stress index in the arterial
convex with a larger angle.
PMID- 28689954
TI - Surgical Intervention for Peripheral Artery Disease Does Not Improve Patient
Compliance with Recommended Medical Therapy.
AB - BACKGROUND: Nonadherence to smoking abstinence, antiplatelet therapy, and statin
therapy in patients with peripheral artery disease (PAD) is associated with worse
long-term outcomes. We hypothesized that patients who underwent invasive
revascularization procedures would be more likely to adhere to these therapies
than patients who were managed medically. METHODS: Prospective survey-based
interviews pertaining to medication and behavioral compliance of patients with
symptomatic PAD were performed. Specifically, adherence to smoking cessation,
antiplatelet therapy, and antilipid therapy was evaluated. A retrospective review
of the electronic medical record was then performed to obtain procedural data and
divide patients into medically managed or surgically managed (open
revascularization, percutaneous revascularization, amputation) cohorts. RESULTS:
One hundred patients met criteria for inclusion and took part in the study.
Overall, 62% were nonsmokers, and 59.1% of those with a history of smoking had
quit; 66.7% were adherent to statin therapy; and 72.7% were adherent to
antiplatelet therapy. Among patients treated with or without surgery,
respectively, there was no difference in regards to rates of smoking abstinence
(64.8% vs. 55.2%, P = 0.37), successful smoking cessation (61.5% vs. 53.6%, P =
0.51), antiplatelet adherence (73.9% vs. 74.1%, P = 0.99), or statin adherence
(65.2% vs. 70.4%, P = 0.24). Major amputation was also not associated with
adherence to these therapies. CONCLUSIONS: Surgical revascularization does not
influence the likelihood of adherence to smoking abstinence, smoking cessation,
antiplatelet therapy, or statin therapy in patients with symptomatic PAD.
Patients should be counseled regarding revascularization options with the
understanding that their likelihood of medical treatment compliance will be
unaffected by any proposed intervention.
PMID- 28689955
TI - Flow-diverting Stent in the Treatment of Cervical Carotid Dissection and
Pseudoaneurysm: Review of Literature and Case Report.
AB - BACKGROUND: The endovascular technique has been recommended over the past few
years to extracranial carotid dissection and pseudoaneurysm with promising
results, especially after medical therapy failure. Flow-diverting stents are an
alternative for complex cases. These stents have proven to be effective treatment
devices for intracranial aneurysms. METHODS: The reference list of Pham's
systematic review, published in 2011, and Seward's literature review, published
in 2015, was considered, as well as all new articles with eligible features.
Search was conducted on specific databases: MEDLINE and Literatura Latino
Americana e do Caribe em Ciencias da Saude. RESULTS: For carotid dissection and
pseudoaneurysm, our review yielded 3 published articles including 12 patients.
The technical success rate of flow-diverting stent was 100% with no procedural
complication described. Mean clinical follow-up was 27.2 months (range 5-48), and
in 5 months' angiographic follow-up, all lesions had healed. No new neurological
events were reported during the clinical follow-up. CONCLUSIONS: Flow diverter
stent use on intracranial and peripheral vascular surgery demonstrates
satisfactory initial results, but it is still under investigation. There are very
few cases treated till now and the initial results with flow-diverting stents to
cervical carotid dissection are promising. In well-selected cases, where simple
embolization or conventional stent is not appropriate, this technic may be
considered.
PMID- 28689956
TI - Crossing the Rubicon: A Closer Look at the Pedal Loop Technique.
AB - The outcome of peripheral bypass surgery in patients at risk of limb loss is
largely influenced by the anatomical integrity of the plantar arch. For this
reason, in the last few decades, this area has been considered to be a sensitive
territory, rarely approached surgically, and virtually untouchable by any
endovascular activities. This hesitance was related to the possible damage to the
thin dorsalis pedis, deep plantar, and lateral plantar arteries, together with
the crucial metatarsal and digital branches arising from the arch. Twelve years
ago, I argued that this area was anatomically very similar to the left anterior
descending coronary artery and, thus, suitable for recanalization using standard
endovascular coronary technique. Since its initial case, the pedal loop (PL)
technique has become a very popular and glamorous procedure, likely performed in
thousands of cases worldwide, additionally proving its efficacy in 2 large
patient-registry retrospective analyses. Although the procedure is considered
quite complex, from a technical point of view, it has almost no reliable
alternatives in vascular and endovascular daily practice. However, by focusing
attention on 12 well-established key points of the PL technique, it is likely
that such may favor its diffusion among vascular surgeons and endovascular
specialists.
PMID- 28689957
TI - Video-Assisted Thoracoscopic Sympathectomy for Facial Hyperhidrosis: The
Influence of the Main Site of Complaint.
AB - INTRODUCTION: Facial hyperhidrosis (FH) may lead patients to a significantly
impaired quality of life (QOL). Video-assisted thoracoscopic sympathectomy (VATS)
is reserved for more severe cases refractory to common first-line agents. The aim
of this study was to evaluate the efficacy of VATS for FH and to compare the
results between patients with facial hyperhidrosis as main complaint (FHMC) and
patients with facial hyperhidrosis as nonmain complaint (FHNMC). METHODS: This
was a retrospective study based on medical chart analysis from March 2000 to
January 2014: 40 patients with FHMC and 136 patients with FHNMC. Patients
underwent VATS at the T2, T3, or T4 level, according to the main site of
complaint. We assessed improvement in QOL, improvement in hyperhidrosis, and
presence of complications and side effects, notably compensatory hyperhidrosis
(CH). RESULTS: Patients with FHMC reported greater improvement in FH (97.1%
versus 93.6%; P = 0.006) but had lower improvement in QOL (78.2% versus 92.7%; P
= 0.024) compared to patients with FHNMC. For patients with FHNMC, any degree of
improvement in FH was reported by 100%, almost 95%, and nearly 80% of the
patients who underwent VATS at the T2, T3, and T4 level, respectively (P =
0.039). Pain and CH were reported by more than 61% and 92% of the patients,
respectively, with no statistical difference between both groups. CONCLUSIONS:
Patients with FHMC, despite the greater improvement in FH, experienced lower
improvement in QOL compared to patients with FHNMC. CH was the most frequent side
effect in both groups, affecting more than 92% of the patients.
PMID- 28689958
TI - One-Stage Endovascular Treatment of a Symptomatic Penetrating Ulcer in the
Lusorian Artery and an AAA: A Challenging Case in a Rare Entity.
AB - INTRODUCTION: We report a case of a 57-year-old man with a successful total
endovascular treatment of a symptomatic penetrating arterial ulcer (PAU) of a
lusorian artery (LA) together with a standard endovascular abdominal aortic
aneurysm (AAA) repair. The LA is an aberrant subclavian artery and a congenital
aortic arch anomaly with a reported prevalence of 0.4-2.6%. Typical for the base
of the LA is a Kommerell diverticulum making an endovascular approach even more
difficult. METHODS: The patient was admitted to our hospital due to an unspecific
retrosternal and hypopharyngeal pulsation feeling. The contrast computed
tomography scan revealed a PAU in the middle of the aberrant right subclavian
artery, apart from the size progression of an asymptomatic and followed-up AAA.
Beside a standard abdominal endovascular aortic repair (EVAR), a total
endovascular PAU exclusion was achieved using an Endurant tapered leg extension.
The system was released in a back-table procedure and then remounted reversed on
the system which now could be introduced via a transverse arteriotomy of the
right axillary artery. RESULTS: The technical result was excellent, no endoleak
was observed, and the symptoms disappeared immediately. The patient was
discharged symptom free after 5 days. SUMMARY: This is so far the first reported
total endovascular therapy of a symptomatic PAU of an LA. There are no tapered
leg extensions or main bodies with a necessary working length for a femoral
approach and correct sizing at the same time available on the market. The
technical success was, therefore, based on the possibility of releasing and
remounting parts of the Endurant Stent Graft System in emergency cases in a back
table setting. Although this is off-label use in experienced hands, it is easy to
handle and can surely help the endovascular surgeon in some challenging situation
where no standard stent-graft system is available.
PMID- 28689959
TI - Removal of nutrients and pharmaceuticals and personal care products from
wastewater using periphyton photobioreactors.
AB - In this work, periphyton photobioreactors were built and were used for the
treatment of synthetic wastewater spiked with PPCPs under different operational
conditions. The removal rates of total nitrogen were relatively stable and varied
from 39% to 77% overtime in different treatments. However, the removal rates of
soluble reactive phosphorus decreased overtime from 42% to 68% on day 2 to 15.8%
to 44% on day 22. For the selected PPCPs, only bisphenol A was effectively
removed (72%-86.4%), hydrochlorothiazide and ibuprofen were moderately removed
(26.2%-48.7%), and carbamazepine and gemfibrozil were poorly removed (6.45%
20.6%). Longer hydraulic retention time enhanced the treatment efficiency but
illumination period showed contrasting effects on the removal of the nutrients
and the PPCPs.
PMID- 28689960
TI - Scorpion Stings in Jordan: An Update.
AB - OBJECTIVE: Scorpionism is an endemic public health problem in Jordan encountered
by health providers in all parts of the country. This study updates
epidemiological data on scorpion sting encounters in Jordan. METHODS: Data on
scorpion sting encounters were obtained from government and military hospitals
around the country, and the National Drug and Poison Information Center (NDPIC).
P values and 95% confidence intervals (CIs) were calculated using SPSS
Professional Statistics Package version 22 (IBM Corp., Armonk, NY) program.
RESULTS: Epidemiological data on 1205 scorpion sting cases reported between 2006
and 2012 are reported. Male to female ratio was 1.18:1, aged 23.3+/-16 (mean+/
SD) and 26.4+/-16.9 years for males and females, respectively. Age groups between
1 to 20 years old constituted 44.6% of the total sting encounters, while adults
aged >30 years constituted 30%. Scorpion sting encounters peaked in July (22.5%)
and August (23%), with the lowest numbers of recorded cases in February and
January (1.6 and 1.9%, respectively). Scorpion stings occurred mostly outdoors
(66%). Medical complications associated with scorpion sting cases included fever,
difficulty in breathing, drowsiness and dizziness, and numbness, while severe
complications include respiratory failure and tachycardia. Hospitalization
required 1 to 3 days among admitted patients with no fatalities. CONCLUSIONS:
Scorpion stings remain a medical problem in Jordan that requires more attention
by health providers. Reporting of scorpion sting cases should be enforced from
all healthcare centers throughout the country to better understand the
epidemiology and health implications of human encounters.
PMID- 28689961
TI - Pregabalin reduces cisplatin-induced mechanical allodynia in rats.
AB - Although cisplatin (CDDP) is a key drug in cancer chemotherapy, CDDP-induced
peripheral neuropathy is a dose-limiting factor. We previously reported that CDDP
induced peripheral neuropathy, which progressed from allodynia to hypoalgesia,
was ameliorated by the administration of CDDP to rats at a specific time.
However, mechanical allodynia cannot be prevented therapeutically. Pregabalin
(PGN) is used to suppress neuropathic pain from herpes zoster and diabetes.
Therefore, we investigated the effects of PGN on CDDP-induced mechanical
allodynia in rats. CDDP (4 mg/kg) was administered intravenously to male Sprague
Dawley rats at 5:00 once a week for 2 weeks, while saline was given to the
control group. PGN (10 mg/kg/day) was administered orally twice a day at 8:00 and
20:00, and distilled water was given to the control group. The von Frey and hot
plate tests were performed to assess CDDP-induced peripheral neuropathy.
Withdrawal thresholds were significantly greater than those in with the CDDP
alone group when PGN was administered before and after the onset of CDDP-induced
mechanical allodynia. Furthermore, CDDP-induced mechanical allodynia was
suppressed by the administration of PGN only. These results demonstrate that PGN
effectively ameliorates CDDP-induced mechanical allodynia during the
administration of PGN.
PMID- 28689962
TI - Astaxanthin analogs, adonixanthin and lycopene, activate Nrf2 to prevent light
induced photoreceptor degeneration.
AB - Carotenoids, in particular astaxanthin, possess potent antioxidant capabilities.
Astaxanthin also induces NF-E2-related factor 2 (Nrf2), which plays a major
regulatory role in the antioxidative response. However, little is known whether
the carotenoid, by-products of astaxanthin, activate Nrf2. Toward this end, we
screened eight astaxanthin analogs for Nrf2 activation in murine photoreceptor
cell line, 661 W, by quantitative reverse transcription-polymerase chain reaction
(qRT-PCR). In addition, we monitored cell death in 661 W cells pretreated with
astaxanthin analogs or only pretreated for 6 h with astaxanthin analogs and then
exposed to light. Furthermore, we quantified the reactive oxygen species (ROS)
production. Cell death was quantified after light exposure by nuclear staining.
Nrf2-controlled genes Ho-1, Nqo-1, and Gclm by qRT-PCR and Nrf2 in the nucleus
were upregulated in 661 W cells exposed astaxanthin, adonixanthin, echinenone,
and lycopene. Moreover, astaxanthin, adonixanthin, echinenone, beta-carotene,
adonirubin, and lycopene, but not canthaxanthin, suppressed ROS production and
protected cells against light-induced damage. Moreover, pretreatment with
adonixanthin or lycopene only before light exposure protected against light
induced cell damage and Nrf2 silencing canceled these effects. These findings
indicate that the more potent astaxanthin analogs, adonixanthin and lycopene,
protect against light-induced cell damage through not only an anti-oxidative
response but also through Nrf2 activation.
PMID- 28689963
TI - Development of expanded polytetrafluoroethylene cardiovascular graft platform
based on immobilization of poly lactic-co-glycolic acid nanoparticles using a wet
chemical modification technique.
AB - Expanded polytetrafluoroethylene ePTFE grafts are mostly employed to replace
damaged blood vessels and to restore normal blood flow. However, the dilemma of
early thrombosis, inflammation, and development of biofilms after implantation
limit ePTFE long-term patency and restrict the patient's life quality. In this
study, poly lactic-co-glycolic acid (PLGA) nanoparticles were covalently
immobilized on ePTFE surface for local therapeutic purposes. First, the ePTFE
surface was primarily oxidized by H2O2/H2SO4 solution to create hydroxyl groups.
Consequently, free amino groups were introduced onto ePTFE surface by an
aminolyzation reaction of the activated hydroxyl groups using 3-aminopropyl
triethoxysilane. The produced amino groups were further used as anchor sites for
covalent immobilization of previously prepared PLGA nanoparticles. The functional
groups originated on ePTFE surface were confirmed by FTIR analysis. Furthermore,
the scanning electron microscopy visualization evidenced a homogeneous
distribution pattern of the immobilized PLGA nanoparticles on the surface. The
immobilized PLGA nanoparticles showed stability on ePTFE surface under blood flow
mimetic conditions. Additionally, light microscopy observation confirmed the
biocompatibility of mouse L929 fibroblasts on the nano-coated ePTFE graft. The
cellular adhesion and growth did not reveal remarkable cytotoxicity in the tested
modified ePTFE grafts.
PMID- 28689964
TI - Improving the solubility of nilotinib through novel spray-dried solid
dispersions.
AB - The tyrosine kinase inhibitor nilotinib has a very low aqueous solubility and a
low and variable oral bioavailability. A pharmaceutical formulation with an
improved solubility may enhance the bioavailability and reduce the variability
thereof and of the pharmacokinetics. The aim of this study was to enhance the
solubility of nilotinib by developing a spray dried solid dispersion. A broad
selection of polymer excipients were tested for solubilizing properties. The
spray drying technique was used to produce solid dispersions of nilotinib
hydrochloride (NH) in matrices of the best performing polymers. Both the
dissolution and physicochemical characteristics of the formulations were studied
using a pH-switch dissolution model and conventional microscopic, thermal and
spectrometric techniques. Of the tested spray dried solid dispersions, the ones
containing the co-block polymer Soluplus(r) performed best in terms of in vitro
dissolution properties. Further testing led to an optimized weight ratio of 1:7
(NH:Soluplus(r)) that improved the solubility up to 630-fold compared to
crystalline NH (1.5MUg/mL) in simulated intestinal fluid. This effect can be
attributed to the amorphization of NH and the solubilization of the drug due to
micelle formation. A spray dried solid dispersion formulation of NH with
Soluplus(r) in a ratio of 1:7 was developed that showed a significant increase in
solubility.
PMID- 28689965
TI - pH and NIR-light-responsive magnetic iron oxide nanoparticles for mitochondria
mediated apoptotic cell death induced by chemo-photothermal therapy.
AB - Recently, various therapeutic strategies in anticancer drug development are
focused to reduce adverse side effects and to enhance the therapeutic efficacy.
Mostly, the iron oxide (Fe3O4) nanoparticles have widely been utilized as an
efficient drug delivery system towing to their unique properties such as
excellent magnetic behavior, considerably low toxicity, easy surface modification
and high drug-loading efficacy. In the present study, we synthesized a
multifunctional, DMSA coated, water soluble Fe3O4 nanoparticles (Fe3O4@DMSA/DOX)
for an effective pH and NIR-light triggered delivery of anticancer drug (DOX) in
cancer therapy. The combination of photothermal therapy combined with
chemotherapy results demonstrated that the synthesized Fe3O4@DMSA/DOX is an
excellent candidate for pH- and NIR-light induced phothothermal agent for an
effective delivery of anticancer drug (DOX) into the target sub-cellular level
into the human breast cancer (MDA-MB-231) cells. Furthermore, the Fe3O4@DMSA/DOX
nanoparticles induced an excellent temperature elevation upon NIR light
irradiation and controlled DOX release in vitro. The Fe3O4@DMSA/DOX nanoparticles
exhibited synergistic effect when combining chemotherapy with photothermal
therapy and showed an excellent cell toxicity to MDA-MB-231 cells. In addition,
the combined chemo-photothermal therapy of Fe3O4@DMSA/DOX nanoparticles promoted
an effective cell death by mitochondrial disruption mediated by ROS generation.
Thus, the synthesized Fe3O4@DMSA/DOX nanoparticles could be utilized as potential
anticancer agents for breast cancer treatment.
PMID- 28689966
TI - Comparative in vitro and in vivo taste assessment of liquid praziquantel
formulations.
AB - The taste of pharmaceuticals strongly affects the compliance of patients. This
study investigated the applicability of the electronic tongue and rodent brief
access taste aversion (BATA) model for the bitter compound praziquantel (PZQ) and
taste masked liquid formulations for PZQ. In a comparative study maltodextrin
(MD) Kleptose(r) linecaps 17 was selected as an alternative taste masking agent
to two cyclodextrins; hydroxypropyl-beta-cyclodextrin (HP-beta-CD) and sulfobutyl
ether-beta-cyclodextrin (SBE-beta-CD). A phase solubility study showed the
highest affinity and solubilization capabilities for SBE-beta-CD over HP-beta-CD
and MD, suggesting the highest taste masking ability for SBE-beta-CD. No reliable
results were achieved for PZQ with the Insent electronic tongue. Thus this system
was not used for further evaluation of solutions with MD and CDs to confirm the
results of the solubility study. In contrast the BATA model demonstrated
conclusive responses for the aversiveness of PZQ. The concentration of PZQ
inhibiting 50% of water lick numbers (called IC50 value) was 0.06mg/ml. In
contrast to the phase solubility study, the MD enabled an equal taste masking
effect in vivo in comparison to both CDs. Moreover HP-beta-CD showed superior
taste masking capabilities for PZQ compared to SBE-beta-CD as the SBE-beta-CD
itself was less acceptable for the rodents than HP-beta-CD. In conclusion, the
BATA model was identified as a more efficient taste assessment tool for the pure
PZQ and liquid formulations in contrast to the electronic tongue and the phase
solubility study.
PMID- 28689967
TI - Cyclodextrin-Modified inorganic materials for the construction of nanocarriers.
AB - Inorganic nanoparticles, such as gold, silver, quantum dots and magnetic
nanoparticles, offer a promising way to develop multifunctional nanoparticles for
biomedical applications. Such nanoparticles have the potential to combine in a
single, stable construct various functionalities, simultaneously providing
imaging abilities, thermal therapies and the ability to deliver drugs in a
targeted fashion. An approach for providing drug loading abilities to these
inorganic nanoparticles consists in the modification of their surface with a
coating of cyclodextrins, and thereby endowing the nanoparticles with the
potential of functioning as drug nanocarriers. This review presents the advances
carried out in the preparation of cyclodextrin-contained gold, silver, quantum
dot and magnetic nanoparticles as well as their applications as drug
nanocarriers. The nanoparticle surface can be modified incorporating cyclodextrin
moieties, (i) in situ during the synthesis of the nanoparticles, either using the
cyclodextrin as reducing agent or as stabilizer; or (ii) in a post-synthetic
stage. The cyclodextrin coating contributes to provide biocompatibility to the
nanoparticles and to reduce their cytotoxicity. Cyclodextrin-modified
nanoparticles display a multivalent presentation of quasi-hydrophobic cavities
that enables, not only drug loading in a non-covalent manner, but also the non
covalent assembly of targeting motifs and optical probes. This paper also
provides an overview of some of the reported applications including the in vitro
studies and, to a lesser extent, in vivo studies on the drug-loaded nanoparticles
behavior.
PMID- 28689968
TI - The Ribosomal Protein uL22 Modulates the Shape of the Protein Exit Tunnel.
AB - Erythromycin is a clinically useful antibiotic that binds to an rRNA pocket in
the ribosomal exit tunnel. Commonly, resistance to erythromycin is acquired by
alterations of rRNA nucleotides that interact with the drug. Mutations in the
beta hairpin of ribosomal protein uL22, which is rather distal to the
erythromycin binding site, also generate resistance to the antibiotic. We have
determined the crystal structure of the large ribosomal subunit from Deinococcus
radiodurans with a three amino acid insertion within the beta hairpin of uL22
that renders resistance to erythromycin. The structure reveals a shift of the
beta hairpin of the mutated uL22 toward the interior of the exit tunnel,
triggering a cascade of structural alterations of rRNA nucleotides that propagate
to the erythromycin binding pocket. Our findings support recent studies showing
that the interactions between uL22 and specific sequences within nascent chains
trigger conformational rearrangements in the exit tunnel.
PMID- 28689969
TI - Ancestral Reconstruction Approach to Acetylcholine Receptor Structure and
Function.
AB - Acetylcholine receptors (AChRs) are members of a superfamily of proteins called
pentameric ligand-gated ion channels, which are found in almost all forms of life
and thus have a rich evolutionary history. Muscle-type AChRs are heteropentameric
complexes assembled from four related subunits (alpha, beta, delta, and E). Here
we reconstruct the amino acid sequence of a beta subunit ancestor shared by
humans and cartilaginous fishes (i.e., Torpedo). Then, by resurrecting this
ancestral beta subunit and co-expressing it with human alpha, delta, and E
subunits, we show that despite 132 substitutions, the ancestral subunit is
capable of forming human/ancestral hybrid AChRs. Whole-cell currents demonstrate
that the agonist acetylcholine has reduced potency for hybrid receptors, while
single-channel recordings reveal that hybrid receptors display reduced
conductance and open probability. Our results outline a promising strategy for
studies of AChR evolution aimed at identifying the amino acid origins of AChR
structure and function.
PMID- 28689970
TI - Structural Dynamics of Zika Virus NS2B-NS3 Protease Binding to Dipeptide
Inhibitors.
AB - The NS2B-NS3 viral protease is an attractive drug target against Zika virus
(ZIKV) due to its importance in viral replication and maturation. Here we report
the crystal structure of protease in complex with a dipeptide inhibitor, Acyl-KR
aldehyde (compound 1). The aldehyde moiety forms a covalent bond with the
catalytic Ser135 of NS3. The Arg and Lys residues in the inhibitor occupy the S1
and S2 sites of the protease, respectively. Nuclear magnetic resonance studies
demonstrate that the complex is in the closed conformation in solution. The
chemical environment of residues surrounding the active site is sensitive to the
bound inhibitor as demonstrated by the comparison with two other non-covalent
dipeptides, Acyl-K-Agmatine (compound 2) and Acyl-KR-COOH (compound 3). Removing
the aldehyde moiety in 1 converts the binding mode from a slow to a fast exchange
regime. The structural dynamics information obtained in this study will guide
future drug discovery against ZIKV and other flaviviruses.
PMID- 28689971
TI - Effect of substitution of photo-cross-linker in photochemical cytosine to uracil
transition in DNA.
AB - Genome editing is an important technique for protein engineering, treatment of
genetic disorders, and production of non-native proteins. A shortcoming of
current enzymatic and chemical methods for genome editing is their limited
applicability for in vivo studies. In addition, non-enzymatic methods, such as
photochemical DNA editing using 3-cyanovinylcarbazole (CNVK), require high
temperatures to affect cytosine to uracil transformations. To overcome this
limitation, we developed new photo-cross-linkers based on CNVK, 3
methoxycarbonlycarbazole, 3-carboxyvinylcarbazole, and 3
carbonylamidevinylcarbazole. The use of 3-carboxyvinylcarbazole resulted in
greater acceleration of the deamination reaction than that achieved with CNVK.
The most likely factors affecting the ability of ultrafast photo-responsive
nucleosides to accelerate the deamination reaction are polarity and
hydrophilicity of the oligodeoxyribonucleotides that contain photo-cross-linker.
PMID- 28689972
TI - Selective inhibitors of human mPGES-1 from structure-based computational
screening.
AB - Human mPGES-1 is recognized as a promising target for next generation of anti
inflammatory drugs. Although various mPGES-1 inhibitors have been reported in
literature, few have entered clinical trials and none has been proven clinically
useful so far. It is highly desired for developing the next generation of
therapeutics for inflammation-related diseases to design and discover novel
inhibitors of mPGES-1 with new scaffolds. Here, we report the identification of a
series of new, potent and selective inhibitors of human mPGES-1 with diverse
scaffolds through combined computational and experimental studies. The
computationally modeled binding structures of these new inhibitors of mPGES-1
provide some interesting clues for rational design of modified structures of the
inhibitors to more favorably bind with mPGES-1.
PMID- 28689974
TI - Endoscopic surgery for sinonasal tumors: The transcribriform approach.
AB - Over the past 10 to 20 years, endoscopic endonasal surgery has become for many
teams the preferred treatment for sinonasal tumors. Technical advances in the
field of surgical instrumentation (good visualization, hemostasis...) and the
progress of imaging guidance (to avoid neurovascular complication) has made those
procedures simpler and safer. Nevertheless, endonasal endoscopic procedures
require a trained surgical team of ENT specialist and neurosurgeon. Endoscopic
endonasal surgery has been reported to be feasible for all types of sinonasal
tumors whether benign tumors such as inverted papillomas, or malignant tumors. In
this paper, we mostly focus on the principles underlying the transcribriform
approach, which is dedicated to the surgery of CSF leaks,
encephaloceles/meningoceles, access to benign intracranial tumors such as
olfactory groove meningiomas, and the resection of sinonasal malignancies with
skull base invasion such as olfactory neuroblastomas.
PMID- 28689973
TI - Structure-based optimization and synthesis of antiviral drug Arbidol analogues
with significantly improved affinity to influenza hemagglutinin.
AB - Influenza is a highly contagious respiratory viral infection responsible for up
to 50,000 deaths per annum in the US alone. The need for new therapeutics with
novel modes of action is of paramount importance. We determined the X-ray
structure of Arbidol with influenza hemagglutinin and found it was located in a
distinct binding pocket. Herein, we report a structure-activity relationship
study based on the co-complex combined with bio-layer interferometry to assess
the binding of our compounds. Addition of a meta-hydroxy group to the thiophenol
moiety of Arbidol to replace a structured water molecule in the binding pocket
resulted in a dramatic increase in affinity against both H3 (1150-fold) and H1
(98-fold) hemagglutinin subtypes. Our analogues represent novel leads to yield
more potent compounds against hemagglutinin that block viral entry.
PMID- 28689975
TI - The medicinal chemistry of Chikungunya virus.
AB - Arthropod-borne viruses (arboviruses) are an important threat to human and animal
health globally. Among these, zoonotic diseases account for billions of cases of
human illness and millions of deaths every year, representing an increasing
public health problem. Chikungunya virus belongs to the genus Alphavirus of the
family Togariridae, and is transmitted mainly by the bite of female mosquitoes of
the Aedes aegypti and/or A. albopictus species. The focus of this review will be
on the medicinal chemistry of Chikungunya virus, including synthetic and natural
products, as well as rationally designed compounds.
PMID- 28689976
TI - CRM1 inhibitory and antiproliferative activities of novel 4'-alkyl substituted
klavuzon derivatives.
AB - Klavuzons are 6-(naphthalen-1-yl) substituted 5,6-dihydro-2H-pyran-2-one
derivatives showing promising antiproliferative activities in variety of cancer
cell lines. In this work, racemic syntheses of nine novel 4'-alkyl substituted
klavuzon derivatives were completed in eight steps and anticancer properties of
these compounds were evaluated. It is found that size of the substituent has
dramatic effect over the potency and selectivity of the cytotoxic activity in
cancerous and healthy pancreatic cell lines. The size of the substituent can also
effect the CRM1 inhibitory properties of klavuzon derivatives. Strong cytotoxic
activity and CRM1 inhibition can be observed only when a small substituent
present at 4'-position of naphthalen-1-yl group. However, these substituents
makes the molecule more cytotoxic in healthy pancreatic cells rather than
cancerous pancreatic cells. Among the tested compounds 1,2,3,4
tetrahydrophenanthren-9-yl substituted lactone was the most cytotoxic compound
and its antiproliferative activity was also tested in 3D spheroids generated from
HuH-7 cell lines.
PMID- 28689977
TI - Design and synthesis of potent and orally active GPR4 antagonists with modulatory
effects on nociception, inflammation, and angiogenesis.
AB - GPR4, a G-protein coupled receptor, functions as a proton sensor being activated
by extracellular acidic pH and has been implicated in playing a key role in
acidosis associated with a variety of inflammatory conditions. An orally active
GPR4 antagonist 39c was developed, starting from a high throughput screening hit
1. The compound shows potent cellular activity and is efficacious in animal
models of angiogenesis, inflammation and pain.
PMID- 28689978
TI - Risk factors for development of surgical site infections among liver
transplantation recipients: An integrative literature review.
AB - BACKGROUND: Surgical site infection (SSI) is an important complication in the
postoperative period of recipients of liver transplantation. The purpose of this
integrative literature review is to summarize the knowledge available about the
risk factors contributing to the development SSI among adults undergoing liver
transplantation. METHODS: We reviewed the Medical Literature Analysis and
Retrieval System Online/PubMed, the Cumulative Index to Nursing and Allied Health
Literature, the Latin American and Caribbean Health Sciences Literature, Scopus,
and Web of Science databases. RESULTS: Two hundred sixteen articles were
identified and the final sample of 9 articles was analyzed in full length. The
SSI rate found in the investigations ranged between 9.6% and 35.5%. Risk factors
for SSI were grouped into categories related to the preoperative period, such as
Model for End-Stage Renal Disease score > 35 and ventilated support on day of
transplant; to the intraoperative period activity, such as transfusion of packed
red blood cells, extended surgical time, hyperglycemia >200 mg/dL, use of
vasopressor drugs, and ascites flow >1 L; and to the donor/recipient
relationship, such as age differences >10 years, ratio of donor liver mass to
recipient body mass < 0.01. Additionally, centers that annually perform <50
transplants appear to have higher rates of SSI. CONCLUSIONS: Few studies have
addressed the subject of SSI in relation to liver transplantation in the
scientific literature. Risk factors for SSI in patients who underwent liver
transplantation vary between institutions.
PMID- 28689979
TI - Assessing the functionality of temporary isolation rooms.
AB - BACKGROUND: Challenges with limited single rooms and isolation facilities in
hospitals have created an opportunity for temporary, portable isolation
technology. This article describes the process used to evaluate the prototype of
a new isolation room (RediRoom; CareStrategic Ltd, Brisbane, Queensland,
Australia) that can be installed in existing hospital ward areas. Our aim is to
assess the functionality of this new room, and in so doing, to evaluate the
methods used. METHODS: We employed a mixed-methods approach involving video
recording, interviews, and objective temperature and humidity measurements within
a crossover interventional study. Participants completed a range of clinical
activities in the RediRoom and a control. The setting for the study was a
clinical ward environment at an Australian higher education institution. RESULTS:
There were similarities between the RediRoom and the control using a range of
measures. The time taken to complete a range of clinical activities in both rooms
was broadly consistent. Network analysis also suggested broad similarities in the
movement of nurses undertaking activities in both rooms. CONCLUSION: Our study
attempted to simulate a clinical environment and clinical activities and provide
the best possible comparison by completing activities sequentially, with
immediate feedback to researchers. Video recording added significant value to the
process because it provided some objectivity. A form of reflexive ethnography
with participants could be of value in similar studies in the future.
PMID- 28689980
TI - The Contribution of Area MT to Visual Motion Perception Depends on Training.
AB - Perceptual decisions require the transformation of raw sensory inputs into
cortical representations suitable for stimulus discrimination. One of the best
known examples of this transformation involves the middle temporal area (MT) of
the primate visual cortex. Area MT provides a robust representation of stimulus
motion, and previous work has shown that it contributes causally to performance
on motion discrimination tasks. Here we report that the strength of this
contribution can be highly plastic: depending on the recent training history,
pharmacological inactivation of MT can severely impair motion discrimination, or
it can have little detectable influence. Further analysis of neural and
behavioral data suggests that training moves the readout of motion information
between MT and lower-level cortical areas. These results show that the
contribution of individual brain regions to conscious perception can shift
flexibly depending on sensory experience.
PMID- 28689981
TI - Thalamic Spindles Promote Memory Formation during Sleep through Triple Phase
Locking of Cortical, Thalamic, and Hippocampal Rhythms.
AB - While the interaction of the cardinal rhythms of non-rapid-eye-movement (NREM)
sleep-the thalamo-cortical spindles, hippocampal ripples, and the cortical slow
oscillations-is thought to be critical for memory consolidation during sleep, the
role spindles play in this interaction is elusive. Combining optogenetics with a
closed-loop stimulation approach in mice, we show here that only thalamic
spindles induced in-phase with cortical slow oscillation up-states, but not out
of-phase-induced spindles, improve consolidation of hippocampus-dependent memory
during sleep. Whereas optogenetically stimulated spindles were as efficient as
spontaneous spindles in nesting hippocampal ripples within their excitable
troughs, stimulation in-phase with the slow oscillation up-state increased
spindle co-occurrence and frontal spindle-ripple co-occurrence, eventually
resulting in increased triple coupling of slow oscillation-spindle-ripple events.
In-phase optogenetic suppression of thalamic spindles impaired hippocampus
dependent memory. Our results suggest a causal role for thalamic sleep spindles
in hippocampus-dependent memory consolidation, conveyed through triple coupling
of slow oscillations, spindles, and ripples.
PMID- 28689982
TI - Network-Level Control of Frequency Tuning in Auditory Cortex.
AB - Lateral inhibition is a fundamental circuit operation that sharpens the tuning
properties of cortical neurons. This operation is classically attributed to an
increase in GABAergic synaptic input triggered by non-preferred stimuli. Here we
use in vivo whole-cell recording and two-photon Ca2+ imaging in awake mice to
show that lateral inhibition shapes frequency tuning in primary auditory cortex
via an unconventional mechanism: non-preferred tones suppress both excitatory and
inhibitory synaptic inputs onto layer 2/3 cells ("network suppression").
Moreover, optogenetic inactivation of inhibitory interneurons elicits a
paradoxical increase in inhibitory synaptic input. These results indicate that
GABAergic interneurons regulate cortical activity indirectly via the suppression
of recurrent excitation. Furthermore, the network suppression underlying lateral
inhibition was blocked by inactivation of somatostatin-expressing interneurons
(SOM cells), but not parvalbumin-expressing interneurons (PV cells). Together,
these findings reveal that SOM cells govern lateral inhibition and control
cortical frequency tuning through the regulation of reverberating recurrent
circuits.
PMID- 28689983
TI - A Novel Neural Prediction Error Found in Anterior Cingulate Cortex Ensembles.
AB - The function of the anterior cingulate cortex (ACC) remains controversial, yet
many theories suggest a role in behavioral adaptation, partly because a robust
event-related potential, the feedback-related negativity (FN), is evoked over the
ACC whenever expectations are violated. We recorded from the ACC as rats
performed a task identical to one that reliably evokes an FN in humans. A subset
of neurons was found that encoded expected outcomes as abstract outcome
representations. The degree to which a reward/non-reward outcome representation
emerged during a trial depended on the history of outcomes that preceded it. A
prediction error was generated on incongruent trials as the ensembles shifted
from representing the expected to the actual outcome, at the same time point we
have previously reported an FN in the local field potential. The results describe
a novel mode of prediction error signaling by ACC neurons that is associated with
the generation of an FN.
PMID- 28689984
TI - Local Cues Establish and Maintain Region-Specific Phenotypes of Basal Ganglia
Microglia.
AB - Microglia play critical roles in tissue homeostasis and can also modulate
neuronal function and synaptic connectivity. In contrast to astrocytes and
oligodendrocytes, which arise from multiple progenitor pools, microglia arise
from yolk sac progenitors and are widely considered to be equivalent throughout
the CNS. However, little is known about basic properties of deep brain microglia,
such as those within the basal ganglia (BG). Here, we show that microglial
anatomical features, lysosome content, membrane properties, and transcriptomes
differ significantly across BG nuclei. Region-specific phenotypes of BG microglia
emerged during the second postnatal week and were re-established following
genetic or pharmacological microglial ablation and repopulation in the adult,
indicating that local cues play an ongoing role in shaping microglial diversity.
These findings demonstrate that microglia in the healthy brain exhibit a spectrum
of distinct functional states and provide a critical foundation for defining
microglial contributions to BG circuit function.
PMID- 28689985
TI - Oxygen consumption and carbon-dioxide recovery kinetics in the prediction of
coronary artery disease severity and outcome.
AB - BACKGROUND: Revascularization appears to be beneficial only in patients with high
levels of ischemia. This study examined the utility of gas analysis during the
recovery phase of cardiopulmonary exercise testing (CPET) in predicting coronary
artery disease (CAD) severity and prognosis. METHODS: 40 Caucasian patients
(21.2% females), mean age 63.5+/-7.6 with significant coronary artery lesions
(>=50%) were studied. Within two months of coronary angiography, CPET on a
treadmill (TM) and recumbent ergometer (RE) were performed on two visits 2-4days
apart; subjects were subsequently followed 32+/-10months. Myocardial wall motion
was recorded by echocardiography at rest and peak exercise. Ischemia was
quantified by the wall motion score index (WMSI). RESULTS: Mean ejection fraction
was 56.7+/-9.6%. Patients with 1-2 stenotic coronary arteries (SCA) showed a
poorer CPET response during the recovery phase than patients with 3-SCA. ROC
analysis revealed the change of carbon-dioxide output (?VCO2) recovery/peak (area
under ROC curve 0.77, p=0.02, Sn=87.5%, Sp=70.4%) and oxygen uptake (?VO2)
recovery/peak during TM CPET (area under ROC curve 0.76, p=0.03, Sn 75.0%, Sp
77.8%) were significant in distinguishing between 1-2-SCA and 3-SCA. The same
variables predicted DeltaWMSI peak/rest on univariate analysis (p<0.05).
Multivariate Cox analysis revealed a high predictive value of ?VO2 recovery/peak
obtained during TM CPET for composite endpoint of cumulative cardiac events
(HR=1.27, CI=1.07-1.51, p=0.008). CONCLUSIONS: The current study suggests CPET
parameters in recovery hold predictive value for CAD severity and prognosis. TM
testing seems to be a better approach in the assessment of CAD severity and
prognosis.
PMID- 28689986
TI - Quaternion-based study of angular velocity of the cardiac vector during
myocardial ischaemia.
AB - BACKGROUND: Early detection of acute ischaemia through non-invasive methods
remains a challenge in health research. Ischaemic condition caused by a decrease
in the blood supply in a cardiac region induces hypoxia and metabolic
abnormalities that contribute to the electrical instability of the heart and to
the development of slow conduction in damaged tissue. METHODS: Herein, a
percutaneous transluminal coronary angiography (PTCA) is considered as a model of
supply ischaemia. We use the concept of quaternion to develop a robust method for
assessing the angular velocity of cardiac vector in the orthogonal XYZ leads
obtained from 92 patients undergoing the PTCA procedure. The maxima of angular
velocity in both ventricular depolarization and repolarization are combined with
traditional linear velocity indexes in order to obtain a detector of ischaemic
episodes (Ischaemia Detector, ID). RESULTS: ID achieves 98%/100% of
sensitivity/specificity when differentiating healthy subjects from patients with
early ischaemia. Furthermore, it also shows high accuracy when the comparison is
made between ischaemic subjects and patients with different non-ischaemic
pathologic ST-deviations which are known to cause false positives, reaching
95%/98% of sensitivity/specificity. Moreover, the study of significant reductions
(p<0.001) of angular velocity components allows extraction of distinct ischaemic
common features which are useful for analyzing the dependence of vectorcardiogram
signal on each site of occlusion. The sensitivity of injury location reaches
values of 88% (RCA), 87% (LAD) and 80% (LCx). CONCLUSIONS: The high performance
of the proposed method establishes a promising outcome for application in
computerized assistance in clinical practice.
PMID- 28689987
TI - Risk factors associated with atherogenic dyslipidemia in the presence of optimal
statin therapy.
AB - BACKGROUND: This study investigated the prevalence of atherogenic dyslipidemia
(AD) in Chinese outpatients whose low-density lipoprotein cholesterol (LDL-C)
levels reached the goals with statin monotherapy and evaluated the
characteristics of these patients. METHODS: An analysis of the Dyslipidemia
International Survey-China study that was carried out at 122 hospitals in China.
Among patients reaching their LDL-C goals, the presence of AD was defined as
triglyceride levels >=1.7mmol/L and/or low levels of high-density lipoprotein
cholesterol (men: <1.0mmol/L; women: <1.3mmol/L). RESULTS: 22,039 patients
receiving statin monotherapy were analyzed. According to the American National
Cholesterol Education Program Adult Treatment Panel III, 13,088 patients reached
LDL-C goals, and 7134 patients of them had AD. Age, male gender, BMI, sedentary
lifestyle, diabetes mellitus, ischemic cerebrovascular disease, serum uric acid
levels, and fasting plasma glucose (all P<0.05) were independently associated
with AD. Based on the Chinese guideline for the management of dyslipidemia,
13,551 patients reached LDL-C goals, and 7719 patients of them had AD. Age, male
gender, BMI, sedentary lifestyle, coronary heart disease, serum uric acid levels,
and fasting plasma glucose (all P<0.05) were independently associated with AD.
The intensity of statin therapy did not affect the prevalence of AD. CONCLUSION:
There was a high prevalence of AD in Chinese patients with optimal statin
treatment. Some risk factors associated with AD were identified, but these
factors were slightly different according to two criteria/guidelines. The
intensity of statin therapy did not reduce the prevalence of AD. A combination
lipid therapy may be more suitable for Chinese patients.
PMID- 28689988
TI - Tip-enhanced Raman scattering for tracking of invasomes in the stratum corneum.
AB - Stratum corneum is the primary skin barrier to percutaneous absorption. Since
1980, topical liposomal formulations have been proposed and successfully employed
for increasing the drug penetration through the skin. There is no clear consensus
on the drug penetration mechanism from topically applied liposomes, despite a
vast amount of research. One of the reasons for the ambiguity is that the
interactions between the stratum corneum and liposomes are in nanoscale, which
makes them difficult to probe. In this study, we employed tip-enhanced Raman
scattering (TERS) to gain a better understanding of the interactions between the
human stratum corneum and topically applied liposomal system called invasomes.
TERS is capable of imaging at nanometer spatial resolution and can provide
structural information at the nanometer scale. A sample preparation technique was
developed and calibrated to enable TERS on complex stratum corneum samples.
Invasomes prepared from a head deuterated phospholipid were employed to aid
identification of topically applied liposomal phospholipid in the stratum
corneum. Results presented in this study give for the first time a strong
spectroscopic evidence along with high-resolution images to show intact invasome
vesicles deep in the stratum corneum upon topical application.
PMID- 28689989
TI - The long variant of human ileal bile acid-binding protein associated with
colorectal cancer exhibits sub-cellular localization and lipid binding behaviour
distinct from those of the common isoform.
AB - BACKGROUND: Ileal bile acid-binding protein, IBABP, participates in the
intracellular trafficking of bile salts and influences their signaling
activities. The recently discovered variant, IBABP-L, bearing an N-terminal 49
amino acid extension, was found to be associated with colorectal cancer and to
protect cancer cells from the cytotoxic effects of deoxycholate. However, the
precise function and the molecular properties of this variant are currently
unknown. METHODS: Bioinformatics tools and confocal microscopy were used to
investigate the sub-cellular localization of IBABP-L; protein dynamics, ligand
binding and interaction with membrane models were studied by 2D NMR and
fluorescence spectroscopy. RESULTS: Based on sub-cellular localization
experiments we conclude that IBABP-L is targeted to the secretory pathway by a 24
residue signal peptide and, upon its cleavage, the mature protein is
constitutively released into the extracellular space. Site-resolved NMR
experiments indicated the distinct preference of primary and secondary bile salts
to form either heterotypic or homotypic complexes with IBABP-L. The presence of
the relatively dynamic N-terminal extension, originating only subtle
conformational perturbations in the globular domain, was found to influence
binding site occupation in IBABP-L as compared to IBABP. Even more pronounced
differences were found in the tendency of the two variants to associate with
phospholipid bilayers. CONCLUSIONS: IBABP-L exhibits different sub-cellular
localization, ligand-binding properties and membrane interaction propensity
compared to the canonical short isoform. GENERAL SIGNIFICANCE: Our results
constitute an essential first step towards an understanding of the role of IBABP
L in bile salt trafficking and signaling under healthy and pathological
conditions.
PMID- 28689990
TI - Graphene oxide nanosheets in complex with cell penetrating peptides for
oligonucleotides delivery.
AB - A new strategy for gene transfection using the nanocarrier of cell penetrating
peptides (CPPs; PepFect14 (PF14) or PepFect14 (PF14) (PF221)) in complex with
graphene oxide (GO) is reported. GO complexed with CPPs and plasmid (pGL3),
splice correction oligonucleotides (SCO) or small interfering RNA (siRNA) are
performed. Data show adsorption of CPPs and oligonucleotides on the top of the
graphenic lamellar without any observed change of the particle size of GO. GO
mitigates the cytotoxicity of CPPs and improves the material biocompatibility.
Complexes of GO-pGL3-CPPs (CPPs; PF14 or PF221) offer 2.1-2.5 fold increase of
the cell transfection compared to pGL3-CPPs (CPPs; PF14 or PF221). GO-SCO-PF14
assemblies effectively transfect the cells with an increase of >10-25 fold
compared to the transfection using PF14. The concentration of GO plays a
significant role in the material nanotoxicity and the transfection efficiency.
The results open a new horizon in the gene treatment using CPPs and offer a
simple strategy for further investigations.
PMID- 28689991
TI - Ubiquitin phosphorylated at Ser57 hyper-activates parkin.
AB - Malfunction of the ubiquitin (Ub) E3 ligase, parkin, leads to defects in
mitophagy and protein quality control linked to Parkinson's disease. Parkin
activity is stimulated by phosphorylation of Ub at Ser65 (pUbS65). Since the
upstream kinase is only known for Ser65 (PINK1), the biochemical function of
other phosphorylation sites on Ub remain largely unknown. We used fluorescently
labelled and site-specifically phosphorylated Ub substrates to quantitatively
relate the position and stoichiometry of Ub phosphorylation to parkin activation.
Fluorescence measurements show that pUbS65-stimulated parkin is 5-fold more
active than auto-inhibited and un-stimulated parkin, which catalyzes a basal
level of auto-ubiquitination. We consistently observed a low but detectable level
of parkin activity with pUbS12. Strikingly, pUbS57 hyper-activates parkin, and
our data demonstrate that parkin is able to selectively synthesize poly-pUbS57
chains, even when 90% of the Ub in the reaction is un-phosphorylated. We further
found that parkin ubiquitinates its physiological substrate Miro-1 with chains
solely composed of pUbS65 and more efficiently with pUbS57 chains. Parkin hyper
activation by pUbS57 demonstrates the first PINK1-independent route to active
parkin, revealing the roles of multiple ubiquitin phosphorylation sites in
governing parkin stimulation and catalytic activity. This article is part of a
Special Issue entitled "Biochemistry of Synthetic Biology - Recent Developments"
Guest Editor: Dr. Ilka Heinemann and Dr. Patrick O'Donoghue.
PMID- 28689992
TI - Characteristics of palliative care consultation at an academic level one trauma
center.
AB - BACKGROUND: The current status of palliative care consultation for trauma
patients has not been well characterized. We hypothesized that palliative care
consultation currently is requested for patients too late to have any clinical
significance. METHODS: A retrospective chart review was performed for
traumatically injured patients' >=18 years of age who received palliative care
consultation at an academic medical center during a one-year period. RESULTS: The
palliative care team evaluated 82 patients with a median age of 60 years. Pain
and end of life were the most common reasons for consultation; interventions
performed included delirium management and discussions about nutritional support.
For decedents, median interval from palliative care consultation to death was 1
day. Twenty seven patients died (11 in the palliative care unit, 16 in an ICU).
Nine patients were discharged to hospice. CONCLUSIONS: Most consultations were
performed for pain and end of life management in the last 24 h of life,
demonstrating the opportunity to engage the palliative care service earlier in
the course of hospitalization.
PMID- 28689993
TI - MAPT Genetic Variation and Neuronal Maturity Alter Isoform Expression Affecting
Axonal Transport in iPSC-Derived Dopamine Neurons.
AB - The H1 haplotype of the microtubule-associated protein tau (MAPT) locus is
genetically associated with neurodegenerative diseases, including Parkinson's
disease (PD), and affects gene expression and splicing. However, the functional
impact on neurons of such expression differences has yet to be fully elucidated.
Here, we employ extended maturation phases during differentiation of induced
pluripotent stem cells (iPSCs) into mature dopaminergic neuronal cultures to
obtain cultures expressing all six adult tau protein isoforms. After 6 months of
maturation, levels of exon 3+ and exon 10+ transcripts approach those of adult
brain. Mature dopaminergic neuronal cultures display haplotype differences in
expression, with H1 expressing 22% higher levels of MAPT transcripts than H2 and
H2 expressing 2-fold greater exon 3+ transcripts than H1. Furthermore, knocking
down adult tau protein variants alters axonal transport velocities in mature iPSC
derived dopaminergic neuronal cultures. This work links haplotype-specific MAPT
expression with a biologically functional outcome relevant for PD.
PMID- 28689995
TI - SIRT1 Enhances the Survival of Human Embryonic Stem Cells by Promoting DNA
Repair.
AB - Human embryonic stem cells (hESCs) hold great promise for the treatment of many
incurable diseases. Sirtuin1 (SIRT1), a class III histone deacetylase, is
abundantly expressed in hESCs and is known to regulate early differentiation and
telomere elongation. Here, we show that downregulation of SIRT1 promotes cell
death in hESCs, but not in differentiated cells, and the SIRT1-inhibition
mediated cell death is preceded by increased DNA damage. This increased DNA
damage is at least partially due to decreased levels of DNA repair enzymes such
as MSH2, MSH6, and APEX1. Furthermore, SIRT1 inhibition causes p53 activation,
which eventually leads to DNA damage-induced apoptosis of hESCs. This study
provides valuable insights into the mechanism of SIRT1-mediated hESC survival and
should contribute to the development of safe and effective cell therapies.
PMID- 28689994
TI - RBP4-STRA6 Pathway Drives Cancer Stem Cell Maintenance and Mediates High-Fat Diet
Induced Colon Carcinogenesis.
AB - The transmembrane protein, STRA6, functions as a vitamin A transporter and a
cytokine receptor when activated by vitamin A-bound serum retinol binding protein
4 (RBP4). STRA6 activation transduces a JAK2-STAT3 signaling cascade and promotes
tumorigenesis in a xenograft mouse model of colon cancer. We show here that RBP4
and STRA6 expression is associated with poor oncologic prognosis. Downregulating
STRA6 or RBP4 in colon cancer cells decreased the fraction of cancer stem cells
and their sphere and tumor initiation frequency. Furthermore, we show that high
fat diet (HFD) increases LGR5 expression and promotes tumor growth in a xenograft
model independent of obesity. HFD increased STRA6 levels, and downregulation of
STRA6 delays and impairs tumor initiation, tumor growth, and expression of
stemness markers. Together, these data demonstrate a key role of STRA6 and RBP4
in the maintenance of colon cancer self-renewal and that this pathway is an
important link through which consumption of HFD contributes to colon
carcinogenesis.
PMID- 28689996
TI - Adult Mouse Liver Contains Two Distinct Populations of Cholangiocytes.
AB - The biliary system plays an important role in several acquired and genetic
disorders of the liver. We have previously shown that biliary duct epithelium
contains cells giving rise to proliferative Lgr5+ organoids in vitro. However, it
remained unknown whether all biliary cells or only a specific subset had this
clonogenic activity. The cell surface protease ST14 was identified as a positive
marker for the clonogenic subset of cholangiocytes and was used to separate
clonogenic and non-clonogenic duct cells by fluorescence-activated cell sorting.
Only ST14hi duct cells had the ability to generate organoids that could be
serially passaged. The gene expression profiles of clonogenic and non-clonogenic
duct cells were similar, but several hundred genes were differentially expressed.
RNA fluorescence in situ hybridization showed that clonogenic duct cells are
interspersed among regular biliary epithelium at a ~1:3 ratio. We conclude that
adult murine cholangiocytes can be subdivided into two populations differing in
their proliferative capacity.
PMID- 28689997
TI - Dynamic Reorganization of Nucleosome Positioning in Somatic Cells after Transfer
into Porcine Enucleated Oocytes.
AB - The nucleosome, the fundamental structural unit of chromatin, is a critical
regulator of gene expression. The mechanisms governing changes to nucleosome
occupancy and positioning during somatic cell reprogramming remain poorly
understood. We established a method for generating genome-wide nucleosome maps of
porcine embryonic fibroblasts (PEF), reconstructed 1-cell embryos generated by
somatic cell nuclear transfer (SCNT), and fertilized zygotes (FZ) using MNase
sequencing with only 1,000 cells. We found that donor PEF chromatin, especially X
chromosome, became more open after transfer into porcine oocytes and nucleosome
occupancy decreased in promoters but increased in the genic regions. Nucleosome
arrangements around transcriptional start sites of genes with different
expression levels in somatic cells tended to become transcriptionally silent in
SCNT; however, some pluripotency genes adopted transcriptionally active
nucleosome arrangements. FZ and SCNT had similar characteristics, unlike PEF.
This study reveals the dynamics and importance of nucleosome positioning and
chromatin organization early after reprogramming.
PMID- 28689998
TI - Association between Serum Uric Acid Level and Activity of Daily Living in
Japanese Patients with Ischemic Stroke.
AB - BACKGROUND: An association between serum uric acid and outcomes of ischemic
stroke has been reported, but the results are controversial. The aim of this
study is to clarify how uric acid may affect activities of daily living after
acute ischemic stroke. METHODS: Consecutive Japanese patients with acute ischemic
stroke were analyzed. Serum uric acid quartiles and activities of daily living at
hospitalization and discharge in men and women were examined. Activities of daily
living were evaluated using the modified Rankin scale score, and a score of 3 or
higher was defined as poor activities of daily living. P values less than .05
were considered significant. RESULTS: A total of 987 patients with acute ischemic
stroke (591 men; mean age, 72.3 years) were analyzed in this study. We observed a
U-shaped relationship between serum uric acid and poor activities of daily living
in both men and women at hospitalization and discharge. Multivariate analysis
demonstrated that the first quartile group of serum uric acid was significantly
associated with poor activities of daily living in both men and women, using the
third quartile group as the reference. CONCLUSIONS: Lower serum uric acid can be
a marker for predicting poor activities of daily living in patients with acute
ischemic stroke, irrespective of sex.
PMID- 28689999
TI - Real-World Outcomes of Acute Ischemic Stroke Treatment with Intravenous
Recombinant Tissue Plasminogen Activator.
AB - BACKGROUND AND PURPOSE: In clinical trials, intravenous (IV) recombinant tissue
type plasminogen activator (rt-PA) reduces the likelihood of disability if given
within 3 hours of acute ischemic stroke. This study compared real-world outcomes
between patients treated and patients not treated with IV rt-PA. METHODS: In this
retrospective study, United States-based neurologists randomly selected eligible
acute ischemic stroke patients from their charts who were and were not treated
with IV rt-PA. Mortality, hospital readmission, and independence were compared
between patients treated and patients not treated with IV rt-PA using Kaplan
Meier curves, log-rank tests, and Cox proportional hazards models. RESULTS: A
total of 1026 charts were reviewed with a median follow-up time of 15.5 months.
Pretreatment stroke severity, as measured by the National Institutes of Health
Stroke Scale, was comparable between cohorts (IV rt-PA =11.7; non-rt-PA = 11.3; P
= .165). IV rt-PA patients experienced significantly longer survival (P = .013),
delayed hospital readmission (P = .012), and shorter time to independence (P <
.001) compared with patients not treated with rt-PA. After adjusting for baseline
characteristics, IV rt-PA patients had significantly lower mortality (hazard
ratio [95% confidence interval] = .52 [.30, .90]) and greater rates of
independence (hazard ratio [95% confidence interval] = 1.42 [1.17, 1.71]) than
patients not treated with rt-PA. CONCLUSIONS: This real-world study indicated
that acute ischemic stroke patients treated with IV rt-PA experience long-term
clinical benefits in survival and functional status.
PMID- 28690000
TI - "I'm Not Gonna Pull the Rug out From Under You": Patient-Provider Communication
About Opioid Tapering.
AB - : In response to increases in harms associated with prescription opioids, opioid
prescribing has come under greater scrutiny, leading many health care
organizations and providers to consider or mandate opioid dose reductions
(tapering) for patients with chronic pain. Communicating about tapering can be
difficult, particularly for patients receiving long-term opioids who perceive
benefits and are using their medications as prescribed. Because of the importance
of effective patient-provider communication for pain management and recent health
system-level initiatives and provider practices to taper opioids, this study used
qualitative methods to understand communication processes related to opioid
tapering, to identify best practices and opportunities for improvement. Up to 3
clinic visits per patient were audio-recorded, and individual interviews were
conducted with patients and their providers. Four major themes emerged: 1)
explaining-patients needed to understand individualized reasons for tapering,
beyond general, population-level concerns such as addiction potential, 2)
negotiating-patients needed to have input, even if it was simply the rate of
tapering, 3) managing difficult conversations-when patients and providers did not
reach a shared understanding, difficulties and misunderstandings arose, and 4)
nonabandonment-patients needed to know that their providers would not abandon
them throughout the tapering process. PERSPECTIVE: Although opioid tapering can
be challenging, helping patients to understand individualized reasons for
tapering, encouraging patients to have input into the process, and assuring
patients they would not be abandoned all appear to facilitate optimal
communication about tapering.
PMID- 28690002
TI - Reply to Howlett and Mortimer
PMID- 28690001
TI - Synergistic Interaction Between Dexmedetomidine and Ulinastatin Against
Vincristine-Induced Neuropathic Pain in Rats.
AB - : Antimicrotubulin chemotherapeutic agents such as vincristine (VCR), often
induce peripheral neuropathic pain. It is usually permanent and seriously harmful
to cancer patients' quality of life and can result in the hampering of clinical
treatments. Currently, there is no definitive therapy, and many of the drugs
approved for the treatment of other neuropathic pain have shown little or no
analgesic effect. It is therefore vital to find new and novel therapeutic
strategies for patients suffering from chemotherapeutic agent-induced neuropathic
pain to improve patients' quality of life. This study shows that intrathecal
injections of dexmedetomidine (DEX), or intraperitoneally administered
ulinastatin (UTI) significantly reduces Sprague Dawley rats' mechanical allodynia
induced by VCR via upregulation of interleukin-10 expression and activating the
alpha2-adrenergic receptor in dorsal root ganglion (DRG). Moreover, when combined
there is a synergistic interaction between DEX and UTI, which acts against VCR
induced neuropathic pain. This synergistic interaction between DEX and UTI may be
partly attributed to a common analgesic pathway in which the upregulation of
interleukin -10 plays an important role via activating alpha2-adrenergic receptor
in rat dorsal root ganglion. The combined use of DEX and UTI does not affect the
rat's blood pressure, heart rate, sedation, motor score, spatial learning, or
memory function. All of these show that the combined use of DEX and UTI is an
effective method in relieving VCR-induced neuropathic pain in rats. PERSPECTIVE:
This article documents the synergistic interaction between 2 widely used drugs,
DEX and UTI, against VCR-induced neuropathic pain. The results provide a
potential target and novel drug administrated method for the clinical treatment
of chemotherapy-induced peripheral neuropathic pain.
PMID- 28690003
TI - Artistic Clues to Psychogenic Tremor Using Pen and Paper.
PMID- 28690004
TI - Health Insurance Coverage among Young Adult Survivors of Pediatric Heart
Transplantation.
AB - OBJECTIVE: To describe the change in health insurance after heart transplantation
among adolescents, and characterize the implications of this change for long-term
transplant outcomes. STUDY DESIGN: Patients age 15-18 years receiving first-time
heart transplantation between 1999 and 2011 were identified in the United Network
for Organ Sharing registry and included in the analysis if they survived at least
5 years. The primary exposure was change or continuity of health insurance
coverage between the time of transplant and the 5-year follow-up. Cox
proportional hazards models were used to determine the association between
insurance status change and long-term (>5 years) patient and graft survival.
RESULTS: The analysis included 366 patients (age 16 +/- 1 years at transplant),
of whom 205 (56%) had continuous private insurance; 96 (26%) had continuous
public insurance; and 65 (18%) had a change in insurance status. In stepwise
multivariable Cox regression, change in insurance status was associated with
greater mortality hazard, compared with continuous private insurance (hazard
ratio = 1.9; 95% CI: 1.1, 3.2; P = .016), whereas long-term patient and graft
survival did not differ between patients with continuous public and continuous
private insurance. CONCLUSIONS: Continuity of insurance coverage is associated
with improved long-term clinical outcomes among adolescent heart transplant
recipients who survive into adulthood.
PMID- 28690005
TI - Pediatric Emergency Department Resource Utilization among Children with Primary
Care Clinic Contact in the Preceding 2 Days: A Cross-Sectional Study.
AB - OBJECTIVES: To characterize pediatric patient contacts with their primary care
clinic in the 2 days preceding a visit to the emergency department (ED) and
explore how the type of clinic contact relates to ED resource use. STUDY DESIGN:
We conducted a retrospective chart review of 368 pediatric ED visits in the first
7 days of each month, from September 2012 to August 2013. Visits were included if
the family contacted their child's general pediatric clinic in the study health
system in the 2 days preceding the ED visit. Descriptive statistics were
calculated. Primary outcomes were ED resource use (tests, treatments) and
disposition (admission or discharge). Outcomes by type of clinic contact were
compared with chi2 statistics. RESULTS: Of 1116 records with ED visits in the 12
study weeks extracted from the electronic medical record, 368 ED visits met
inclusion criteria. Most ED visits followed a single clinic contact (78.8%). Of
the 474 clinic contacts, 149 were in-person visits, 216 phone calls when clinic
was open, and 109 phone calls when clinic was closed. ED visits that followed an
in-person clinic contact with advice to go to the ED had significantly greater
rates of testing and admission than those advised to go to the ED after phone
contact and those never advised to go to the ED. CONCLUSIONS: In-person clinic
visits with advice to go to the ED were associated with the greatest ED resource
use. Limitations include a study of a single health system without a uniform
process for triaging patients to the ED across clinics.
PMID- 28690006
TI - Respose to the letter to the editor: "Is there a real consensus among
anaesthetists and surgeons about the neuromuscular block? Methodological
considerations about the ACHILLES study".
PMID- 28690007
TI - Bioreactor-induced mesenchymal progenitor cell differentiation and elastic fiber
assembly in engineered vascular tissues.
AB - : In vitro maturation of engineered vascular tissues (EVT) requires the
appropriate incorporation of smooth muscle cells (SMC) and extracellular matrix
(ECM) components similar to native arteries. To this end, the aim of the current
study was to fabricate 4mm inner diameter vascular tissues using mesenchymal
progenitor cells seeded into tubular scaffolds. A dual-pump bioreactor operating
either in perfusion or pulsatile perfusion mode was used to generate
physiological-like stimuli to promote progenitor cell differentiation,
extracellular elastin production, and tissue maturation. Our data demonstrated
that pulsatile forces and perfusion of 3D tubular constructs from both the
lumenal and ablumenal sides with culture media significantly improved tissue
assembly, effectively inducing mesenchymal progenitor cell differentiation to
SMCs with contemporaneous elastin production. With bioreactor cultivation,
progenitor cells differentiated toward smooth muscle lineage characterized by the
expression of smooth muscle (SM)-specific markers smooth muscle alpha actin (SM
alpha-actin) and smooth muscle myosin heavy chain (SM-MHC). More importantly,
pulsatile perfusion bioreactor cultivation enhanced the synthesis of tropoelastin
and its extracellular cross-linking into elastic fiber compared with static
culture controls. Taken together, the current study demonstrated progenitor cell
differentiation and vascular tissue assembly, and provides insights into elastin
synthesis and assembly to fibers. STATEMENT OF SIGNIFICANCE: Incorporation of
elastin into engineered vascular tissues represents a critical design goal for
both mechanical and biological functions. In the present study, we seeded porous
tubular scaffolds with multipotent mesenchymal progenitor cells and cultured in
dual-pump pulsatile perfusion bioreactor. Physiological-like stimuli generated by
bioreactor not only induced mesenchymal progenitor cell differentiation to
vascular smooth muscle lineage but also actively promoted elastin synthesis and
fiber assembly. Gene expression and protein synthesis analyses coupled with
histological and immunofluorescence staining revealed that elastin-containing
vascular tissues were fabricated. More importantly, co-localization and co
immunoprecipitation experiments demonstrated that elastin and fibrillin-1 were
abundant throughout the cross-section of the tissue constructs suggesting a
process of elastin protein crosslinking. This study paves a way forward to
engineer elastin-containing functional vascular substitutes from multipotent
progenitor cells in a bioreactor.
PMID- 28690008
TI - Laminin mimetic peptide nanofibers regenerate acute muscle defect.
AB - : Skeletal muscle cells are terminally differentiated and require the activation
of muscle progenitor (satellite) cells for their regeneration. There is a
clinical need for faster and more efficient treatment methods for acute muscle
injuries, and the stimulation of satellite cell proliferation is promising in
this context. In this study, we designed and synthesized a laminin-mimetic
bioactive peptide (LM/E-PA) system that is capable of accelerating satellite cell
activation by emulating the structure and function of laminin, a major protein of
the basal membrane of the skeletal muscle. The LM/E-PA nanofibers enhance
myogenic differentiation in vitro and the clinical relevance of the laminin
mimetic bioactive scaffold system was demonstrated further by assessing its
effect on the regeneration of acute muscle injury in a rat model. Laminin mimetic
peptide nanofibers significantly promoted satellite cell activation in skeletal
muscle and accelerated myofibrillar regeneration following acute muscle injury.
In addition, the LM/E-PA scaffold treatment significantly reduced the time
required for the structural and functional repair of skeletal muscle. This study
represents one of the first examples of molecular- and tissue-level regeneration
of skeletal muscle facilitated by bioactive peptide nanofibers following acute
muscle injury. SIGNIFICANCE STATEMENT: Sports, heavy lifting and other strength
intensive tasks are ubiquitous in modern life and likely to cause acute skeletal
muscle injury. Speeding up regeneration of skeletal muscle injuries would not
only shorten the duration of recovery for the patient, but also support the
general health and functionality of the repaired muscle tissue. In this work, we
designed and synthesized a laminin-mimetic nanosystem to enhance muscle
regeneration. We tested its activity in a rat tibialis anterior muscle by
injecting the bioactive nanosystem. The evaluation of the regeneration and
differentiation capacity of skeletal muscle suggested that the laminin-mimetic
nanosystem enhances skeletal muscle regeneration and provides a suitable platform
that is highly promising for the regeneration of acute muscle injuries. This work
demonstrates for the first time that laminin-mimetic self-assembled peptide
nanosystems facilitate myogenic differentiation in vivo without the need for
additional treatment.
PMID- 28690009
TI - Amorphous surface layer versus transient amorphous precursor phase in bone - A
case study investigated by solid-state NMR spectroscopy.
AB - : The presence of an amorphous surface layer that coats a crystalline core has
been proposed for many biominerals, including bone mineral. In parallel,
transient amorphous precursor phases have been proposed in various
biomineralization processes, including bone biomineralization. Here we propose a
methodology to investigate the origin of these amorphous environments taking the
bone tissue as a key example. This study relies on the investigation of a bone
tissue sample and its comparison with synthetic calcium phosphate samples,
including a stoichiometric apatite, an amorphous calcium phosphate sample, and
two different biomimetic apatites. To reveal if the amorphous environments in
bone originate from an amorphous surface layer or a transient amorphous precursor
phase, a combined solid-state nuclear magnetic resonance (NMR) experiment has
been used. The latter consists of a double cross polarization 1H->31P->1H pulse
sequence followed by a 1H magnetization exchange pulse sequence. The presence of
an amorphous surface layer has been investigated through the study of the
biomimetic apatites; while the presence of a transient amorphous precursor phase
in the form of amorphous calcium phosphate particles has been mimicked with the
help of a physical mixture of stoichiometric apatite and amorphous calcium
phosphate. The NMR results show that the amorphous and the crystalline
environments detected in our bone tissue sample belong to the same particle. The
presence of an amorphous surface layer that coats the apatitic core of bone
apatite particles has been unambiguously confirmed, and it is certain that this
amorphous surface layer has strong implication on bone tissue biogenesis and
regeneration. STATEMENT OF SIGNIFICANCE: Questions still persist on the
structural organization of bone and biomimetic apatites. The existing model
proposes a core/shell structure, with an amorphous surface layer coating a
crystalline bulk. The accuracy of this model is still debated because amorphous
calcium phosphate (ACP) environments could also arise from a transient amorphous
precursor phase of apatite. Here, we provide an NMR spectroscopy methodology to
reveal the origin of these ACP environments in bone mineral or in biomimetic
apatite. The 1H magnetization exchange between protons arising from amorphous and
crystalline domains shows unambiguously that an ACP layer coats the apatitic
crystalline core of bone et biomimetic apatite platelets.
PMID- 28690010
TI - Tailoring surface nanoroughness of electrospun scaffolds for skeletal tissue
engineering.
AB - : Electrospun scaffolds provide a promising approach for tissue engineering as
they mimic the physical properties of extracellular matrix. Previous studies have
demonstrated that electrospun scaffolds with porous features on the surface of
single fibers, enhanced cellular attachment and proliferation. Yet, little is
known about the effect of such topographical cues on cellular differentiation.
Here, we aimed at investigating the influence of surface roughness of electrospun
scaffolds on skeletal differentiation of human mesenchymal stromal cells (hMSCs).
Scanning electron microscopy (SEM) and atomic force microscopy (AFM) analysis
showed that the surface nanoroughness of fibers was successfully regulated via
humidity control of the electrospinning environment. Gene expression analysis
revealed that a higher surface roughness (roughness average (Ra)=71.0+/-11.0nm)
supported more induction of osteogenic genes such as osteopontin (OPN), bone
morphogenetic protein 2 (BMP2), and runt-related transcription factor 2 (RUNX2),
while a lower surface roughness (Ra=14.3+/-2.5nm) demonstrated higher expression
of other osteogenic genes including bone sialoprotein (BSP), collagen type I
(COL1A1) and osteocalcin (OCN). Interestingly, a lower surface roughness
(Ra=14.3+/-2.5nm) better supported chondrogenic gene expression of hMSCs at day 7
compared to higher surface roughness (Ra=71.0+/-11.0nm). Taken together,
modulating surface roughness of 3D scaffolds appears to be a significant factor
in scaffold design for the control of skeletal differentiation of hMSCs.
STATEMENT OF SIGNIFICANCE: Tissue engineering scaffolds having specific
topographical cues offer exciting possibilities for stimulating cells
differentiation and growth of new tissue. Although electrospun scaffolds have
been extensively investigated in tissue engineering and regenerative medicine,
little is known about the influence of introducing nanoroughness on their surface
for cellular differentiation. The present study provides a method to engineer
electrospun scaffolds with tailoring surface nanoroughness and investigates the
effect of such topographical cues on the process of human mesenchymal stromal
cells differentiation into osteoblasts and chondrocytes linages. This strategy
may help the design of nanostructured scaffolds for skeletal tissue engineering.
PMID- 28690011
TI - LUME-Meso: Design and Rationale of the Phase III Part of a Placebo-Controlled
Study of Nintedanib and Pemetrexed/Cisplatin Followed by Maintenance Nintedanib
in Patients With Unresectable Malignant Pleural Mesothelioma.
AB - Malignant pleural mesothelioma (MPM) is a rare but aggressive disease: median
survival is 6 to 9 months if untreated. Standard first-line treatment for
patients with unresectable MPM is cisplatin/pemetrexed, with a median overall
survival (OS) of approximately 1 year. Improvements in first-line treatment
options are needed. With the benefit of combining bevacizumab with standard
therapy shown in the Mesothelioma Avastin Cisplatin Pemetrexed Study (MAPS),
vascular endothelial growth factor (VEGF) pathway inhibition has gained renewed
interest as a treatment approach. Nintedanib is an oral angiokinase inhibitor
targeting multiple signaling pathways implicated in the pathogenesis of MPM,
including the VEGF receptor. The phase III part of the international, phase
II/III LUME-Meso study is evaluating the efficacy and safety of nintedanib plus
pemetrexed/cisplatin in patients with unresectable epithelioid MPM. Originally,
this was a double-blind, randomized, phase II exploratory study and was amended
to include a confirmatory phase III part following the recommendation of an
internal Data Monitoring Committee and review of phase II data. The phase III
part plans to enroll 450 chemotherapy-naive patients, who will be randomized to
receive pemetrexed/cisplatin on day 1 and nintedanib or placebo on days 2 to 21,
for a maximum of 6 cycles. Patients without disease progression who are eligible
to continue study treatment will receive maintenance treatment with nintedanib or
placebo until disease progression or undue toxicity. The primary end point is
progression-free survival; OS is the key secondary end point. The study will use
an adaptive design, including an interim analysis to reassess the number of OS
events required to ensure sufficient power for OS analysis. The study is
currently enrolling patients.
PMID- 28690012
TI - Prognostic Value of Metabolic Parameters of Metastatic Lymph Nodes on 18F-FDG
PET/CT in Patients With Limited-stage Small-cell Lung Cancer With Lymph Node
Involvement.
AB - INTRODUCTION: We assessed the prognostic value of the metabolic parameters of
different lesions, including primary tumors and metastatic lymph nodes (LNs),
measured by fluorine-18 fluorodeoxyglucose positron emission tomography
(PET)/computed tomography in patients with limited-stage small-cell lung cancer
(LS-SCLC) with LN metastasis. MATERIALS AND METHODS: The present retrospective
study included 46 patients with clinical stage II-III N1-N2 LS-SCLC who had
undergone pretreatment fluorine-18 fluorodeoxyglucose PET/computed tomography
scanning from January 2011 to December 2014. All patients underwent complete
first-line therapy (concurrent chemoradiotherapy and prophylactic cranial
irradiation). The metabolic parameters, including maximal standardized uptake
value, mean standardized uptake value, metabolic tumor volume (MTV), and total
lesion glycolysis (TLG) values of the PTs and metastatic LNs were measured on
PET. Kaplan-Meier survival curves were used for evaluation of progression-free
survival (PFS) and overall survival (OS). Univariate and multivariate Cox
proportional hazards models were used to analyze the prognostic factors. RESULTS:
The median OS and PFS were 25.9 months (range, 8.2-63.5 months) and 21 months
(range, 6.4-55.3 months), respectively. Univariate analysis demonstrated that the
Eastern Cooperative Oncology Group performance status, N1 station involvement,
subcarinal LN metastasis, LN MTV, LN TLG, sum of the MTV, and summary of the TLG
were significant predictive factors (P < .05). The Eastern Cooperative Oncology
Group performance status, subcarinal nodal metastasis, LN MTV, and LN TLG were
independent predictive factors of PFS and OS on multivariate analysis.
CONCLUSION: The metabolic parameters of metastatic LNs, other than lung lesions,
are independent prognostic factors in patients with LS-SCLC with LN metastasis.
These parameters could further stratify the prognosis of these patients, and
these findings might provide functional imaging evidence for the future study of
the mechanisms of metastasis.
PMID- 28690013
TI - Peptides derived from plasma proteins released by bothropasin, a metalloprotease
present in the Bothrops jararaca venom.
AB - Viperid snake venoms contain proteases that affect hemostasis by degrading
important proteins such as those that participate in the coagulation cascade. The
Bothrops jararaca venom presents as its main components metallo and serine
proteases, which comprise around 65% of the venom composition. Bothropasin is a
hemorrhagic metalloprotease from the B. jararaca venom which causes disruption of
the basement membrane of the vascular endothelium, resulting in bleeding.
Although the bothropasin ability to degrade plasmatic and extracellular matrix
proteins in vitro has been described, the primary sequence of the released
peptides is unknown. This research study presents the peptide identification from
both fibrinogen and fibronectin, generated by bothropasin proteolytic activity.
Among the fibrinogen derived peptides identified by mass spectrometry, analogous
of endogenous products like the fibrinopeptides A and B were found, as well as
other sequences described in the literature with vasoactive or antiangiogenic
properties. A series of peptides derived from fibronectin by the action of
bothropasin were described, and for most of them no biological activity has been
described. However, exceptionally a peptide that is known as a bond site for B
cells was found. This study indicates that, beyond to the degradation of human
proteins, bothropasin can generate bioactive peptides, which may participate in
the envenoming process by Bothrops snakes. Also important, the knowledge of the
formed peptides, based on the cleavage sites of the hydrolyzed proteins, provided
the opportunity to study the primary specificity of bothropasin.
PMID- 28690014
TI - Psychiatric symptoms in myoclonus-dystonia syndrome are just concomitant features
regardless of the SGCE gene mutation.
AB - INTRODUCTION: Among myoclonus-dystonia syndrome (MD) patients, psychiatric
disorders including depression, anxiety, alcohol dependence, obsessive-compulsive
disorder (OCD) and panic disorder have been frequently reported to be related
with the epsilon-sarcoglycan gene (SGCE) mutation. However, the rate of
psychiatric disorders has not been compared between MD patients with the SGCE
mutation (SGCE (+)) and without the SGCE mutation (SGCE (-)). We analyzed the
psychiatric data in both SGCE (+) and SGCE (-) MD patients to determine the
association of the SGCE mutation with psychiatric disorders in MD. METHODS:
Twenty-six MD patients who fulfilled the Grunewald's criteria and underwent a
SGCE gene study were enrolled. Patients were divided into two groups according to
their SGCE status (SGCE (+) and SGCE (-) group). They were systematically
assessed using a standardized protocol including motor severity scales and
psychiatric questionnaires for depression, anxiety, alcohol dependence, OCD and
panic disorder. RESULTS: Fifteen SGCE (+) and eleven SGCE (-) patients were
enrolled. Mean age at onset, disease duration, family history, alcohol
responsiveness and motor severity were not different between the SGCE (+) and
SGCE (-) group. Although more than half (53.8%) of all the MD patients had
psychiatric symptoms, there were no significant differences between the SGCE (+)
and SGCE (-) group in terms of their psychiatric questionnaire scores and rate of
psychiatric disorders. CONCLUSIONS: Psychiatric features are not likely to be
related with the SGCE mutation itself but just bespeak disability in clinical MD
syndrome regardless of the SGCE mutation.
PMID- 28690015
TI - Causes of failure of pallidal deep brain stimulation in cases with pre-operative
diagnosis of isolated dystonia.
AB - INTRODUCTION: Pallidal deep brain stimulation (GPi-DBS) is an effective therapy
for isolated dystonia, but 10-20% of patients show improvement below 25-30%. We
here investigated causes of insufficient response to GPi-DBS in isolated dystonia
in a cross-sectional study. METHODS: Patients with isolated dystonia at time of
surgery, and <30% improvement on the Burke-Fahn-Marsden dystonia-rating-scale
(BFMDRS) after >=6 months of continuous GPi-DBS were videotaped ON and OFF
stimulation, and history, preoperative videos, brain MRI, medical records,
stimulation settings, stimulation system integrity, lead location, and genetic
information were obtained and reviewed by an expert panel. RESULTS: 22 patients
from 11 centres were included (8 men, 14 women; 9 generalized, 9 segmental, 3
focal, 1 bibrachial dystonia; mean (range): age 48.7 (25-72) years, disease
duration 22.0 (2-40) years, DBS duration 45.5 (6-131) months). Mean BFMDRS-score
was 31.7 (4-93) preoperatively and 32.3 (5-101) postoperatively. Half of the
patients (n = 11) had poor lead positioning alone or in combination with other
problems (combined with: other disease n = 6, functional dystonia n = 1, other
problems n = 2). Other problems were disease other than isolated inherited or
idiopathic dystonia (n = 5), fixed deformities (n = 2), functional dystonia (n =
3), and other causes (n = 1). Excluding patients with poor lead location from
further analysis, non-isolated dystonia accounted for 45.5%, functional dystonia
for 27.3%, and fixed deformities for 18.2%. In patients with true isolated
dystonia, lead location was the most frequent problem. CONCLUSION: After
exclusion of lead placement and stimulation programming issues, non-isolated
dystonia, functional dystonia and fixed deformities account for the majority of
GPi-DBS failures in dystonia.
PMID- 28690016
TI - Partial titanium mesh explantation cured post-cranioplasty implant-associated
scalp infection.
AB - Titanium mesh cranioplasty is routinely used worldwide for skull defect patients
given its advantages, such as stability and biocompatibility. However, there are
very few reports concerning the treatment of implant-associated scalp infection,
which is one of the most common complications. The aim of the study is to
retrospectively evaluate a novel operation technique for the treatment of
titanium mesh-associated scalp infection post-cranioplasty, namely partial
titanium mesh explantation (PTME). A retrospective study was conducted in all
patients who underwent surgical treatment for implant-associated scalp infection
from January 2012 to September 2016 in our hospital. In total, 17 patients were
selected for study analysis among 231 patients who underwent cranioplasty. The
treatment success rate of PTME was 85.7%. There was no statistically significant
difference in demographics and characteristics except for follow-up length of
time between the PTME group and TTME (total titanium mesh explantation) group
(Non-paired Student's t-test, P=0.037). While, The PTME group exhibited a
significantly reduced skull defect area post-operation compared with the TTME
group (Non-paired Student's t-test, P=0.002). Moreover, post-PTME skull area also
exhibited a significantly reduced skull defect area compared with the pre
cranioplasty area in the same patient (Non-paired Student's t-test, P=0.006).
Compared with traditional surgical treatment of implant-associated scalp
infection, PTME combined with strict debridement and antibiotic therapy can cure
implant-associated scalp infection. Moreover, PTME could preserve sufficient
titanium mesh for brain protection and cosmesis.
PMID- 28690017
TI - Diagnosis and treatment for pure aqueductal tumor.
AB - Pure aqueductal tumor (PAT) typically originates from pure aqueductal region and
is extremely rare. It is radiographically similar to tectal glioma. We examined
two patients with PATs who were diagnosed with pilocytic astrocytoma and rosette
forming glioneuronal tumor. Both cases showed a progressive clinical course. It
is important to distinguish between PAT and tectal glioma by radiographic imaging
because the treatment strategy is different. While observation is common for
tectal gliomas, a biopsy is recommended at the same time of endoscopic third
ventriculostomy for PAT with hydrocephalus. Low-grade PATs show an aggressive
clinical course in some cases. Our two cases also showed aggressive course in
spite of no genetic aggressive mutations. Sagittal view by constructive
interference in steady state (CISS) imaging was helpful to make an accurate
diagnosis of PAT. Close observation is needed if PAT is diagnosed as low-grade
tumor.
PMID- 28690018
TI - Adaptations of lumbar biomechanics after four weeks of running training with
minimalist footwear and technique guidance: Implications for running-related
lower back pain.
AB - OBJECTIVES: To investigate the changes in lumbar kinematic and paraspinal muscle
activation before, during, and after a 4-week minimalist running training.
DESIGN: Prospective cohort study. SETTING: University research laboratory.
PARTICIPANTS: Seventeen habitually shod recreational runners who run 10-50 km per
week. MAIN OUTCOME MEASURES: During stance phases of running, sagittal lumbar
kinematics was recorded using an electrogoniometer, and activities of the lumbar
paraspinal muscles were assessed by electromyography. Runners were asked to run
at a prescribed speed (3.1 m/s) and a self-selected speed. RESULTS: For the 3.1
m/s running speed, significant differences were found in the calculated mean
lumbar posture (p = 0.001) during the stance phase, including a more extended
lumbar posture after minimalist running training. A significant reduction in the
contralateral lumbar paraspinal muscle activation was also observed (p = 0.039).
For the preferred running speed, similar findings of a more extended lumbar
posture (p = 0.002) and a reduction in contralateral lumbar paraspinal muscle
activation (p = 0.047) were observed. CONCLUSION: A 4-week minimalist running
training program produced significant changes in lumbar biomechanics during
running. Specifically, runners adopted a more extended lumbar posture and reduced
lumbar paraspinal muscle activation. These findings may have clinical
implications for treating individuals with running-related lower back pain.
PMID- 28690019
TI - Evaluation of the benefits of exercise on cognition in major depressive disorder.
AB - BACKGROUND: Cognitive impairment is increasingly recognized as a significant
symptom in patients with major depressive disorder (MDD). While exercise is
already recommended in many treatment guidelines for patients with MDD and has
been shown to improve cognition in other disorders (e.g., Alzheimer's,
Parkinson's, schizophrenia), limited research is available evaluating the effect
of exercise on cognition in MDD. METHODS: We provide a narrative review of
existing literature regarding the effect(s) of exercise on cognition across
several neurodegenerative and psychiatric diseases, and particularly in MDD, with
specific emphasis on study design and methodology that may impair adequate
synthesis of the results. We also describe mechanisms by which exercise may
improve cognition in depression and other brain disorders. RESULTS: Of existing
studies with MDD, data are equivocal, as some are supportive of improved
cognition, whereas others demonstrate no benefit. Several limitations were noted,
including insufficiently-powered designs, variability in interventions examined
(e.g., aerobic, anaerobic, mind-body) or control groups, lack of attention to the
status of baseline cognitive impairment, and/or heterogeneity across outcome
measures and clinical characteristics. CONCLUSIONS: While preliminary results
suggest the potential for exercise as a beneficial treatment or augmentation
strategy for impaired cognition in MDD, the aforementioned limitations
necessitate further investigation.
PMID- 28690020
TI - Cardiac Society of Australia and New Zealand Position Statement: Coronary Artery
Calcium Scoring.
AB - Coronary Artery Calcium Scoring (CAC) is a non-invasive quantitation of coronary
artery calcification using computed tomography (CT). It is a marker of
atherosclerotic plaque burden and an independent predictor of future myocardial
infarction and mortality. Coronary Artery Calcium Scoring provides incremental
risk information beyond traditional risk calculators (eg. Framingham Risk Score).
Its use for risk stratification is confined to primary prevention of
cardiovascular events, and can be considered as "individualised coronary risk
scoring" for those not considered to be of high or low risk. Medical
practitioners should carefully counsel patients prior to CAC. Coronary Artery
Calcium Scoring should only be undertaken if an alteration in therapy including
embarking on pharmacotherapy is being considered based on the test result.
Patient Groups to Consider Coronary Calcium Scoring: Patient Groups in Whom
Coronary Calcium Scoring Should Not be Considered: Coronary Artery Calcium
Scoring is not recommended for patients who are: Interpretation of CAC CAC=0 A
zero score confers a very low risk of death, <1% at 10 years. CAC=1-100 Low risk,
<10% CAC=101-400 Intermediate risk, 10-20% CAC=101-400 & >75th centile.
Moderately high risk, 15-20% CAC >400 High risk, >20% Management Recommendations
Based on CAC Optimal diet and lifestyle measures are encouraged in all risk
groups and form the basis of primary prevention strategies. Patients with
moderately-high or high risk based on CAC score are recommended to receive
preventative medical therapy such as aspirin and statins. The evidence for
pharmacotherapy is less robust in patients at intermediate levels of CAC 100-400,
with modest benefit for aspirin use; though statins may be reasonable if they are
above 75th centile. Aspirin and statins are generally not recommended in patients
with CAC <100. Repeat CAC Testing In patients with a CAC of 0, a repeat CAC may
be considered in 5 years but not sooner. In patients with positive calcium score,
routine re-scanning is not currently recommended. However, an annual increase in
CAC of >15% or annual increase of CAC >100 units are predictive of future
myocardial infarction and mortality. Cost Effectiveness of CAC Based Primary
Prevention Recommendations: There is currently no data in Australia and New
Zealand that CAC is cost-effective in informing primary prevention decisions.
Given the cost of testing is currently borne entirely by the patient, discussion
regarding the implications of CAC results should occur before CAC is recommended
and undertaken.
PMID- 28690021
TI - Transcatheter Aortic Valve Implantation in Nonagenarians: Procedural Outcome and
Mid-Term Results.
AB - BACKGROUND: For nonagenarians with symptomatic severe aortic stenosis
transcatheter aortic valve implantation (TAVI) has become a feasible therapeutic
option. Therefore, the aim of this study was to evaluate the procedural outcomes
and mid-term follow-up in this patient group and compare this to octogenarians.
METHODS: From 1359 patients who underwent TAVI at our institution between March
2009 and February 2016, 82 patients were nonagenarians and 912 were
octogenarians. In nonagenarians, mean age was 91.9+/-1.4years and compared to
octogenarians showed a significantly higher logistic EuroScore (27.7+/-14.8% vs.
23.1+/-14.4, p=0.005) and STS Score (8.5+/-4.8% vs. 6.3+/-6.7, p=0.001). RESULTS:
There were no significant differences with regard to stroke rate, pacemaker
implantation rate and major vascular complications between the two groups. Thirty
day mortality was 9.8% in nonagenarians and 4.1% in octogenarians (p=0.04). At 1
year, all-cause mortality increased to 30.9% vs. 18.6% (n.s.). CONCLUSION:
Nonagenarians showed an increased periprocedural mortality during TAVI and higher
mortality in follow-up compared to octogenarians. Age alone is not a predictive
factor but indication for treatment should be carefully evaluated by the heart
team on an individual basis.
PMID- 28690022
TI - Absence of Myostatin Improves Cardiac Function Following Myocardial Infarction.
AB - BACKGROUND: Myostatin inhibits the development of skeletal muscle and regulates
the proliferation of skeletal muscle fibroblasts. However, the role of myostatin
in regulating cardiac muscle or myofibroblasts, specifically in acute myocardial
infarction (MI), is less clear. This study sought to determine whether absence of
myostatin altered left ventricular function post-MI. METHODS: Myostatin-null mice
(Mstn-/-) and wild-type (WT) mice underwent ligation of the left anterior
descending artery to induce MI. Left ventricular function was measured at
baseline, days 1 and 28 post-MI. Immunohistochemistry and immunofluorescence were
obtained at day 28 for cellular proliferation, collagen deposition, and
myofibroblastic activity. RESULTS: Whilst left ventricular function at baseline
and size of infarct were similar, significant differences in favour of Mstn-/-
compared to WT mice post-MI include a greater recovery of ejection fraction
(61.8+/-1.1% vs 57.1+/-2.3%, p<0.01), less collagen deposition (41.9+/-2.8% vs
54.7+/-3.4%, p<0.05), and lower mortality (0 vs. 20%, p<0.05). There was no
difference in the number of BrdU positive cells, percentage of apoptotic
cardiomyocytes, or size of cardiomyocytes post-MI between WT and Mstn-/- mice.
CONCLUSIONS: Absence of myostatin potentially protects the function of the heart
post-MI with improved survival, possibly by limiting extent of fibrosis.
PMID- 28690023
TI - The TyG Index as a Marker of Subclinical Atherosclerosis and Arterial Stiffness
in Lean and Overweight Postmenopausal Women.
AB - BACKGROUND: The present study aims to examine the association of the metabolic
syndrome (MS) as well as of the triglyceride-glucose index (TyG-Index), a novel
marker of insulin resistance, with subclinical atherosclerosis in a cohort of
postmenopausal women, stratified according to their body mass index. METHODS: A
total of 473 informed-consenting, non-diabetic postmenopausal women, without
overt cardiovascular disease, were included in this study. We aimed to compare
the association between structural and functional indices of subclinical
atherosclerosis (i.e. carotid artery intima-media thickness (IMT), flow-mediated
dilation of the brachial artery, pulse wave velocity (PWV)) with the TyG-index or
MS, separately for lean and overweight/obese women. RESULTS: The TyG-Index
correlated significantly with carotid IMT (r=0.155, p=0.012) and PWV (r=0.157,
p=0.013) only in the group of lean women. Multivariate analysis showed that
subclinical atherosclerosis was predicted by MS, in the overweight/obese group
(OR=2.517, 95% CI: 1.078-5.878, p=0.033), and by the TyG-Index the lean group
(OR=3.119, 95% CI: 1.187-8.194, p<0.001). Using a TyG-Index cut-off value of 8.0
in the lean subpopulation, women above the cut-off had 44.1% prevalence of
subclinical atherosclerosis compared to 29.4% in women below the cut-off
(p=0.043). CONCLUSIONS: The TyG-Index is associated with carotid atherosclerosis
and arterial stiffness mainly in lean postmenopausal women, while the MS serves
as a better predictor of subclinical atherosclerosis in overweight/obese women.
The TyG-Index may prove a useful marker for identifying high-risk women in the
normal-weight postmenopausal population.
PMID- 28690024
TI - The p53 gene with emphasis on its paralogues in mosquitoes.
AB - The p53 gene is highly important in human cancers, as it serves as a tumor
suppressor gene. Subsequently, two p53 homologues, i.e., p73 and p63, with high
identity of amino acids were identified, leading to construction of the p53
family. The p53 gene is highly important in human cancer because it usually
transcribes genes that function by causing apoptosis in mammalian cells. In
contrast, p63 and p73 tend to be more important in modulating development than
inducing cell death, even though they share similar protein structures.
Relatively recently, p53 was also identified in mosquitoes and many other insect
species. Uniquely, its structure lacks the sterile alpha motif domain which is a
putative protein-protein interaction domain and exclusively exists at the C
terminal region in p73 and p63 in mammals. A phylogenetic analysis revealed that
the p53 gene derived from mosquitoes is composed of two paralogues, p53-1 and p53
2. Of these, only p53-2 is responsively upregulated by dengue 2 virus (DENV2) in
C6/36 cells which usually survive the infection. This indicates that the p53 gene
is closely related to DENV infection in mosquito cells. The specific significance
of p53-2's involvement in cell survival from virus-induced stress is described
and briefly discussed in this report.
PMID- 28690025
TI - Invasive pneumococcal disease caused by ceftriaxone-resistant Streptococcus
pneumoniae in Taiwan.
AB - BACKGROUND: Invasive pneumococcal disease (IPD) was associated with mortality,
but the risk factors associated with mortality remains controversial. METHODS: A
retrospective cohort study was designed. All patients with IPD from 2011 to 2013
admitted in a medical center were screened and collected for their clinical
presentations and laboratory characteristics. RESULTS: Approximately half of the
134 IPD isolates derived from these patients belonged to three major serotypes
(19A, 6A and 3), which are included in 13-valent pneumococcal conjugate vaccine
(PCV13), but not in 7-valent pneumococcal conjugate vaccine (PCV7). Ceftriaxone
resistance according to non-meningitis criteria was identified in 38% of the IPD
isolates, and was the major independent risk factor associated with inappropriate
initial therapy that subsequently contributed to mortality of the patients.
Infection by serotype 6A, 15B, 19A, 19F, or 23F was the major independent risk
factor associated with ceftriaxone resistance (non-meningitis criteria). 77.6% of
these isolates belonged to additional PCV13 serotypes, with more than 40%
expressing resistance to ceftriaxone. In terms of serotype coverage, PCV13
covered 94.1% of the IPD isolates with ceftriaxone resistance, in comparison to
21.6% only by PCV7. CONCLUSIONS: The increase of ceftriaxone resistance in
pneumococci in part driven by PCV7 vaccination in Taiwan is worrisome. The use of
PCV13 in children as well as in the elderly population is likely to offer
protection from the infection caused by ceftriaxone-resistant pneumococci. It is
important to give an effective drug such as penicillin, fluoroquinolones or
vancomycin in 2 days for improving outcome of IPD patients.
PMID- 28690026
TI - Antimicrobial peptides as potential anti-biofilm agents against multidrug
resistant bacteria.
AB - Bacterial resistance to commonly used drugs has become a global health problem,
causing increased infection cases and mortality rate. One of the main virulence
determinants in many bacterial infections is biofilm formation, which
significantly increases bacterial resistance to antibiotics and innate host
defence. In the search to address the chronic infections caused by biofilms,
antimicrobial peptides (AMP) have been considered as potential alternative agents
to conventional antibiotics. Although AMPs are commonly considered as the
primitive mechanism of immunity and has been extensively studied in insects and
non-vertebrate organisms, there is now increasing evidence that AMPs also play a
crucial role in human immunity. AMPs have exhibited broad-spectrum activity
against many strains of Gram-positive and Gram-negative bacteria, including drug
resistant strains, and fungi. In addition, AMPs also showed synergy with
classical antibiotics, neutralize toxins and are active in animal models. In this
review, the important mechanisms of action and potential of AMPs in the
eradication of biofilm formation in multidrug-resistant pathogen, with the goal
of designing novel antimicrobial therapeutics, are discussed.
PMID- 28690027
TI - Enterobius vermicularis infection and its risk factors among pre-school children
in Taipei, Taiwan.
AB - BACKGROUND: The prevalence of pinworm infection is extremely low in Taipei,
Taiwan. This population study was designed to determine the current status and
the associated risk factors of this infection among pre-school children. METHODS:
Perianal swab specimens were obtained from the parents or guardians using a two
consecutive-day adhesive cellophane perianal swab kit. Information of family
background, personal hygiene, and household sanitary conditions were collected by
asking the parents or guardians to complete a questionnaire. RESULTS: Of 44,163
children, 0.21% was found to infect with pinworm. The positive rate was highest
in Datong (0.59%) and Nangang (0.58%) Districts and lowest in Neihu District
(0.02%). There was no significant difference in the rates by gender (boys 0.24%
and girls 0.19%) or school (kindergartens 0.25% and nurseries 0.17%).
Significantly higher positive rates were found in children having parent with
lower educational level and elder brother(s)/sister(s). Children taking bath by
themselves and those sleeping in bed with matting had significantly higher
positive rates. Five significant independent predictors of pinworm infection were
determined by multivariate analysis: having elder brother(s), having elder
sister(s), infrequent washing hands after using toilet facilities, bathing
without the help of family members, and sleeping on bed with matting. CONCLUSION:
The prevalence of pinworm infection in the pre-school children of Taipei is
extremely low and decreasing. Good hand washing habit should be an important
preventive measure. Transmission of this infection in pre-school children may
occur in the family through their school-age siblings.
PMID- 28690028
TI - Meropenem versus piperacillin/tazobactam with or without immunoglobulin as second
line therapy for febrile neutropenia in pediatric patients.
AB - BACKGROUND: Although survival of children with hematological diseases and cancer
has increased dramatically, life-threatening complications due to bacterial
infections occur in 5-10% of febrile episodes in pediatric cancer patients. A
prospective randomized study was performed to clarify the usefulness of meropenem
(MEPM) and piperacillin/tazobactam (PIPC/TAZ) with or without intravenous
immunoglobulin (IVIG) as second-line therapy for pediatric patients with febrile
neutropenia (FN). PROCEDURE: As first-line therapy for FN, 105 patients with 434
episodes were randomly assigned to receive MEPM or PIPC/TAZ. A total of 71
pediatric patients and 144 episodes were judged as failures and enrolled for
second-line treatment. In second-line treatment, patients were randomized to a
group of MEPM and PIPC/TAZ with or without IVIG. MEPM was given to patients who
received PIPC/TAZ as first-line treatment, and PIPC/TAZ was given to patients who
received MEPM as first-line treatment. RESULTS: The total success rate of second
line therapy was 49.3%. MEPM with or without IVIG was effective in 44.3% of
cases, and PIPC/TAZ with or without IVIG was effective in 55.3%; this difference
was not significant. The success rate in patients with serum IgG under 1000 mg/dl
was 41.3% in the MEPM or PIPC/TAZ group and 64.3% in the MEPM + IVIG or PIPC/TAZ
+ IVIG group (p = 0.028). CONCLUSIONS: The present results suggest that PIPC/TAZ
is as effective as MEPM and safe for second-line treatment of FN in pediatric
patients. Furthermore, IVIG appears very effective for patients with low serum
IgG levels.
PMID- 28690029
TI - High levels of soluble GPR56/ADGRG1 are associated with positive rheumatoid
factor and elevated tumor necrosis factor in patients with rheumatoid arthritis.
AB - BACKGROUND: GPR56/ADGRG1 is a member of the adhesion-class G protein-coupled
receptor (aGPCR) family important in brain development, oncogenesis and tumor
metastasis. Like other aGPCRs, GPR56 is cleaved at the GPCR proteolysis site
(GPS) motif into an N-terminal fragment (NTF) and a C-terminal fragment (CTF).
Existence of soluble GPR56 (sGPR56) has been shown in vitro, however the
underlying mechanism and its pathophysiologic role remains undetermined.
OBJECTIVE: To assess the presence of sGPR56 in human serum using ELISA assay and
compare the serum sGPR56 levels among patients of various chronic inflammatory
diseases and healthy subjects. PATIENTS AND METHODS: In this study, serum samples
from patients with systemic lupus erythematosus (SLE) (n = 57), rheumatoid
arthritis (RA) (n = 95), Sjogren's syndrome (SS) (n = 29), ankylosing spondylitis
(AS) (n = 51), and normal controls (n = 81) were analyzed using sGPR56-specific
ELISA. RESULT: We show that serum sGPR56 levels are increased in patients of RA,
but not in those with SLE, SS and AS. Intriguingly, serum sGPR56 levels in RA
patients correlated with positive rheumatoid factor, a marker of bone erosion and
poor outcome. In addition, an elevated sGPR56 level is also noted in RA patients
with higher tumor necrosis factor level. CONCLUSION: we conclude that sGPR56 is
present in vivo and sGPR56 level is elevated in certain chronic inflammatory
diseases such as RA. Hence, sGPR56 might be considered a potential biomarker for
RA disease progression.
PMID- 28690030
TI - Procalcitonin as a diagnostic biomarker for septic shock and bloodstream
infection in burn patients from the Formosa Fun Coast dust explosion.
AB - BACKGROUND/PURPOSE: Infection is the most common cause of death following burn
injury. The study was conducted to compare the diagnostic value of serum
procalcitonin (PCT) with the other current benchmarks as early predictors of
septic shock and bloodstream infection in burn patients. METHODS: We included 24
patients admitted to the Burn Unit of a medical center from June 2015 to December
2015 from the Formosa Fun Coast dust explosion. We categorized all patients at
initial admission into either sepsis or septic shock groups. Laboratory tests
including the worst PCT and C-reactive protein (CRP) levels, platelet (PLT), and
white blood cell (WBC) count were performed at <48 h after admission. Patients
were also classified in two groups with subsequent bacteremia and non-bacteremia
groups during hospitalization. RESULTS: Significantly higher PCT levels were
observed among participants with septic shock compared to those with sepsis
(47.19 vs. 1.18 ng/mL, respectively; p < 0.001). Patients with bacteremia had
significantly elevated PCT levels compared to patients without bacteremia (29.54
versus 1.81 ng/mL, respectively, p < 0.05). No significant differences were found
in CRP levels, PLT, and WBC count between the two groups. PCT levels showed
reasonable discriminative power (cut-off: 5.12 ng/mL; p = 0.01) in predicting of
bloodstream infection in burn patients and the area under receiver operating
curves was 0.92. CONCLUSIONS: PCT levels can be helpful in determining the septic
shock and bloodstream infection in burn patients but CRP levels, PLT, and WBC
count were of little diagnostic value.
PMID- 28690031
TI - Prevalence of pain in 240 non-ambulatory children with severe cerebral palsy.
AB - BACKGROUND: Several studies have given frequencies of pain in children with
cerebral palsy, but comparing the findings is difficult. We aimed to estimate the
prevalence of pain in non-ambulatory children with cerebral palsy and describe
their characteristics by presence or absence of pain. METHODS: Data were
extracted from an ongoing longitudinal national cohort following non-ambulatory
children with severe cerebral palsy aged 3 to 10years over 10years. We described
and compared data for the first 240 children at inclusion by presence or absence
of pain. Pain was assessed by a visual analog scale and the Douleur Enfant San
Salvadour scales and by investigator interview. RESULTS: Overall, 65 children
experienced pain, for a prevalence of 27.1% (95% confidence interval 22-33%). All
children experiencing pain had orthopaedic pain and 45.6% had pain from another
origin. The main pain sites were hips (43.4%) and feet (26.9%). Joint
mobilisation was the source of pain for 58.3% of children experiencing pain, and
sitting was identified as painful for 10.3%. Pain was greater with scoliosis
(43.1% vs 24.1% with and without pain; P=0.006) and spasticity treatment (32.3%
vs 17.2%; P=0.020). CONCLUSION: Children with cerebral palsy frequently
experience pain and also early pain, mostly articular and orthopedic. The
assessment of pain should be systematic because of its high prevalence.
Interventions to prevent scoliosis, hip luxation, and foot deformities and to
reduce spasticity, such as the use of analgesics before joint mobilization
exercises, may reduce the prevalence of this pain.
PMID- 28690032
TI - Survey on the proper use of an adrenaline auto-injector in 551 Japanese outdoor
workers after Hymenoptera stings.
PMID- 28690033
TI - Schisantherin A attenuates ischemia/reperfusion-induced neuronal injury in rats
via regulation of TLR4 and C5aR1 signaling pathways.
AB - Toll-like receptor 4 (TLR4) and C5aR1 (CD88) have been recognized as potential
therapeutic targets for the reduction of inflammation and secondary damage and
improvement of outcome after ischemia and reperfusion (I/R). The inflammatory
responses which induce cell apoptosis and necrosis after I/R brain injury lead to
a limited process of neural repair. To further comprehend how these targets
function in I/R state, we investigated the pathological changes and TLR4 and
C5aR1 signaling pathways in vitro and in vivo models of I/R brain injury in this
study. Meanwhile, we explored the roles of schisantherin A on I/R brain injury,
and whether it exerted neuroprotective effects by regulating the TLR4 and C5aR1
signaling pathways or not. The results showed that schisantherin A significantly
reduced the neuronal apoptosis induced by oxygen and glucose deprivation and
reperfusion (OGD/R) injury in primary culture of rat cortical neurons. Also,
schisantherin A alleviated neurological deficits, reduced infarct volume,
attenuated oxidation stress, inflammation and apoptosis in ischemic parietal
cortex of rats after middle cerebral artery occlusion and reperfusion (MCAO/R)
injury. Moreover, the activated TLR4 and C5aR1 signaling pathways were inhibited
by schisantherin A treatment. In conclusion, TLR4 and C5aR1 played a vital role
during I/R brain injury in rats, and schisantherin A exhibited neuroprotective
effects by TLR4 and C5aR1 signaling pathways. These findings also provided new
insights that would aid in elucidating the effect of schisantherin A against
cerebral I/R and support the development of schisantherin A as a potential
treatment for ischemic stroke.
PMID- 28690034
TI - Interplay of inflammatory gene expression in pericytes following Japanese
encephalitis virus infection.
AB - Neuroinflammation is a pathological hallmark and has been implicated in the
pathogenesis of Japanese encephalitis. Although brain pericytes show regulatory
effects on neuroinflammation, their involvement in Japanese encephalitis
associated neuroinflammation is not understood. Here, we demonstrated that brain
microvascular pericytes could be an alternative cellular source for the induction
and/or amplification of neuroinflammation caused by Japanese encephalitis virus
(JEV) infection. Infection of cultured pericytes with JEV caused profound
production of IL-6, RANTES, and prostaglandin E2 (PGE2). Mechanistic studies
revealed that JEV infection elicited an elevation of the toll-like receptor 7
(TLR7)/MyD88 signaling axis, leading to the activation of NF-kappaB through IKK
signaling and p65 phosphorylation as well as cAMP response element-binding
protein (CREB) via phosphorylation. We further demonstrated that extracellular
signal-regulated kinase (ERK) could be an alternative regulator in transducing
signals to NF-kappaB, CREB, and cytosolic phospholipase A2 (cPLA2) through the
phosphorylation mechanism. Released IL-6 and RANTES played an active role in the
disruption of endothelial barrier integrity and leukocyte chemotaxis,
respectively. cPLA2/PGE2 had a role in activating NF-kappaB and CREB DNA-binding
activities and inflammatory cytokine transcription via the EP2/cAMP/PKA mechanism
in an autocrine loop. These inflammatory responses and biochemical events were
also detected in the brain of JEV-infected mice. The current findings suggest
that pericytes might have pathological relevance in Japanese encephalitis
associated neuroinflammation through a TLR7-related mechanism. The consequences
of pericyte activation are their ability to initiate and/or amplify inflammatory
cytokine expression by which cellular function of endothelial cells and
leukocytes are regulated in favor of CNS infiltration by leukocytes.
PMID- 28690035
TI - Influenza B meningoencephalitis.
PMID- 28690036
TI - HEV and transfusion-recipient risk.
AB - HEV infections are mainly food- and water-borne but transfusion-transmission has
occurred in both developing and developed countries. The infection is usually
asymptomatic but it can lead to fulminant hepatitis in patients with underlying
liver disease and pregnant women living in developing countries. It also causes
chronic hepatitis E, with progressive fibrosis and cirrhosis, in approximately
60% of immunocompromised patients infected with HEV genotype 3. The risk of a
transfusion-transmitted HEV infection is linked to the frequency of viremia in
blood donors, the donor virus load and the volume of plasma in the final
transfused blood component. Several developed countries have adopted measures to
improve blood safety based on the epidemiology of HEV.
PMID- 28690037
TI - Unacknowledged adverse transfusion reactions: Are they a mine to dig?
AB - OBJECTIVES: Haemovigilance has long tried to characterize and understand
transfusion reactions in order to prevent them. Unacknowledged ones are now a
minority but they question us. Are they the result of incomplete clinical setting
and/or insufficient medical reasoning, or can they contain real new entities we
have not yet understood? MATERIAL AND METHODS: Ten volunteer experts reviewed 30
recent unacknowledged cases. Their diagnostic propositions were compared with
data issued from a five-year repository we have analysed in terms of statistical
links between clinical signs and diagnoses. RESULTS: Experts' opinions are only
quite unanimous in 60% of the cases, and the proposed diagnosis remains
unacknowledged in 53%. Repository comparison shows that signs like pain or
digestive symptoms are far more frequent in unknown reactions. However, it is
more the absence of some other signs which drives to that conclusion, in a
default diagnosis mechanism. CONCLUSION: Errors in transfusion reactions medical
analysis are rare. Unacknowledged cases are more often linked to poor or
unspecific clinical setting. But a particular attention must be paid with
infrequent diagnoses which are far less characterised, like metabolic
complications. Pain high occurrence in unknown cases also commands us to go
further in the characterisation of acute pain transfusion reaction diagnosis,
which is suggested by some authors.
PMID- 28690038
TI - [Transfusion in elderly: Take account frailty].
AB - The conjunction of the demographic aging and the increase in the frequency of
anemia with the advancing age, mean that the number of globular concentrates
delivered each year increases with a consequent heavy pressure on blood
collection. The etiologies of anemia in the elderly are often multifactorial and
their investigation is an indispensable step and prior to any treatment.
Transfusion thresholds, particularly in the elderly, are gradually evolving and a
so-called restrictive strategy is now favored. Immediate and delayed
complications of transfusion are more frequent in the elderly due to
vulnerability factors associated with frailty and the risk of multiple
transfusions. The screening of complications related to transfusion of RBCs is
essential and makes it possible to avoid their recurrence. The impact of
transfusion on the quality of life of elderly patients is not obvious and is a
controversial issue. In addition, transfusion of red blood cells (RBCs) is
accompanied by an increase in health expenditure and an increase in morbidity and
mortality, whose risks can be reduced through alternatives to transfusion.
Longitudinal studies, including elderly subjects, would allow a better
understanding of the issues involved in the transfusion of RBCs in this
population.
PMID- 28690039
TI - Retained Antibiotic Spacers After Total Hip and Knee Arthroplasty Resections:
High Complication Rates.
AB - BACKGROUND: Prolonged retention of an antibiotic spacer is occasionally chosen
during treatment of periprosthetic joint infections after total hip arthroplasty
(THA) and total knee arthroplasty (TKA). The purpose of our study was to evaluate
the outcome of extended spacer retention. METHODS: We reviewed 1106 cases of
periprosthetic joint infection after THA (n = 308) and TKA (n = 798) and
identified 17 (5.5%) retained hip and 34 (4.3%) retained knee spacers. Most
patients (35 of 51, 69%) underwent spacer retention because they were medically
unfit for further surgery. The remaining patients (16 of 51, 31%) had acceptable
function and forewent further surgery. Competing risk analyses, with death as the
competing risk, determined the cumulative incidence of reinfection and spacer
revision. Radiographic analysis and clinical outcomes were analyzed. RESULTS: The
2-year cumulative incidence for reinfection was 7% for retained hip and 13% for
retained knee spacers. The cumulative incidence for all-cause spacer revision was
28% at 4 years for hips and 21% at 2 years for knees. The most common
complications were implant migration and femoral spacer subsidence in the hip
cohort, and supracondylar femur fractures and spacer dislocations in the knee
cohort. The cumulative incidence for radiographic signs of mechanical failure was
72% and 87% at late follow-up for the hip and knee groups, respectively. The
latest Harris Hip Score and Knee Society Score were 62 and 63, respectively.
CONCLUSION: Antibiotic spacer retention is a rare event in the course of planned
2-stage treatment of infected THA or TKA. Failure secondary to recurrent
infection is uncommon; however, failure for mechanical reasons is frequent and
clinical outcomes are relatively poor.
PMID- 28690040
TI - Bioactivity of Ceftazidime and Fluconazole Included in Polymethyl Methacrylate
Bone Cement for Use in Arthroplasty.
AB - BACKGROUND: The microorganisms that most frequently cause prosthetic joint
infection are methicillin-resistant Staphylococcus aureus and gram-negative
aerobic bacillus. Studies have documented the efficacy of mixing antibiotics with
polymethyl methacrylate, but that of antifungal drugs has not received much
attention. The objective of this in vitro study was to characterize the elution
profile and bioactivity of ceftazidime and fluconazole when incorporated into
bone cement in proportions intended for prophylaxis and treatment of bone
infections. METHODS: Antibiotic-loaded bone cement cylinders in a proportion of
1:40 and 4:40 (ratio of grams of antibiotic to grams of cement) were assayed.
Drug delivery was investigated in a flow-through dissolution apparatus
(SotaxCE7). To assess bioactivity, antibiotic concentrations were simulated in
the joint space of 1000 patients. Antibacterial properties were evaluated by
counting colony forming units and the inhibition-halo test. RESULTS: The ratio of
released ceftazidime and fluconazole was 453% and 648%, respectively, higher when
used for treatment proportions than prophylaxis proportions. A bioactivity
simulation exercise showed that the efficacy of ceftazidime/fluconazole
determined as the amount of drug is released at the active site in the first 3
days after surgery would depend on the sensitivity of the microorganism and would
increase substantially after drain removal. The microbiology study showed that
biofilm formation by Pseudomonas aeruginosa could be a problem when ceftazidime
was used in treatment or prophylaxis proportions. CONCLUSION: Our in vitro
findings suggest that ceftazidime and fluconazole can be added into polymethyl
methacrylate for the prevention/treatment of infections associated to joint
surgery. Their efficacy depends on the sensitivity of the microorganism causing
the infection.
PMID- 28690042
TI - The impact of subchondral bone cysts on local bone stresses in the medial femoral
condyle of the equine stifle joint.
AB - Subchondral lucency (SCL), also referred to as subchondral bone cysts, can cause
clinical problems in horses and humans. In humans, SCLs occur in youths and
adolescents [1] due to mechanical factors (often related to athletics) and in
skeletally mature individuals secondary to osteoarthritis (OA). In horses, SCL
most commonly occurs in the medial femoral condyle (MFC) of growing horses
(without OA), and causes lameness. The cause of equine SCL is debated, but bone
trauma due to overload is the likely mechanism. Investigating the biomechanics of
the healthy and cystic MFC is important to understand cyst growth and to provide
a foundation for new treatment strategies. We hypothesize that SCL alters the
mechanical environment of surrounding bone, which in the presence of continued
loading, may lead to enlargement of the SCL. In this study, we developed and
validated a finite element model of an equine stifle joint and investigated the
stresses associated with varying sizes of SCL. We found substantial differences
in tensile and shear stress at various stages of SCL development that suggest
further bone damage leading to SCL enlargement. These data provide a first step
in understanding of the altered mechanics of subchondral bone surrounding a SCL.
Additional studies may provide the basis for improved treatment strategies for
SCL in young horses, and may improve the understanding of SCL in humans.
PMID- 28690041
TI - Intravenous vs Oral Acetaminophen as an Adjunct to Multimodal Analgesia After
Total Knee Arthroplasty: A Prospective, Randomized, Double-Blind Clinical Trial.
AB - BACKGROUND: The efficacy of intravenous (IV) acetaminophen compared with its oral
formulation for postoperative analgesia is unknown. We hypothesized that the
addition of acetaminophen to a multimodal analgesia regimen would provide
improved pain management in patients after total knee arthroplasty (TKA) and that
the effect of acetaminophen would be variable based on the route of delivery.
METHODS: The study was a single-center, randomized, double-blinded, placebo
controlled clinical trial on the efficacy of IV vs oral acetaminophen in patients
undergoing unilateral TKA. One hundred seventy-four subjects were randomized to
one of the 3 groups: IV acetaminophen group (IV group, n = 57) received 1 g IV
acetaminophen and oral placebo before postanesthesia care unit (PACU) admission;
oral acetaminophen group (PO group, n = 58) received 1 g oral acetaminophen and
volume-matched IV normal saline; placebo group (Placebo group, n = 59) received
oral placebo and volume-matched IV normal saline. Pain scores were obtained every
15 minutes during PACU stay. Average pain scores, maximum pain score, and pain
scores before physical therapy were compared among the 3 groups. Secondary
outcomes included total opiate consumption, time to PACU discharge, time to
rescue analgesia, and time to breakthrough pain. RESULTS: The average PACU pain
score was similar in the IV group (0.56 +/- 0.99 [mean +/- standard deviation])
compared with the PO group (0.67 +/- 1.20; P = .84) and Placebo group (0.58 +/-
0.99; P = .71). Total opiate consumption at 6 hours (0.47 mg hydromorphone
equivalents +/- 0.56 vs 0.54 +/- 0.53 vs 0.54 +/- 0.61; P = .69) and at 24 hours
(1.25 +/- 1.30 vs 1.49 +/- 1.34 vs 1.36 +/- 1.31; P = .46) were also similar
between the IV, PO, and Placebo groups. No significant differences were found
between all groups for any other outcome. CONCLUSION: Neither IV nor oral
acetaminophen provides additional analgesia in the immediate postoperative period
when administered as an adjunct to multimodal analgesia in patients undergoing
TKA in the setting of a spinal anesthetic.
PMID- 28690043
TI - Evaluating and improving the performance of thin film force sensors within body
and device interfaces.
AB - Thin film force sensors are commonly used within biomechanical systems, and at
the interface of the human body and medical and non-medical devices. However,
limited information is available about their performance in such applications.
The aims of this study were to evaluate and determine ways to improve the
performance of thin film (FlexiForce) sensors at the body/device interface. Using
a custom apparatus designed to load the sensors under simulated body/device
conditions, two aspects were explored relating to sensor calibration and
application. The findings revealed accuracy errors of 23.3+/-17.6% for force
measurements at the body/device interface with conventional techniques of sensor
calibration and application. Applying a thin rigid disc between the sensor and
human body and calibrating the sensor using compliant surfaces was found to
substantially reduce measurement errors to 2.9+/-2.0%. The use of alternative
calibration and application procedures is recommended to gain acceptable
measurement performance from thin film force sensors in body/device applications.
PMID- 28690044
TI - A new mathematical model of wrist pulse waveforms characterizes patients with
cardiovascular disease - A pilot study.
AB - The purpose of this study was to analyze and compare a series of measured radial
pulse waves as a function of contact pressure for young and old healthy
volunteers, and old patients with cardiovascular disease. The radial pulse waves
were detected with a pressure sensor and the contact pressure of the sensor was
incremented by 20gf during the signal acquisition. A mathematical model of radial
pulse waveform was developed by using two Gaussian functions modulated by radical
functions and used to fit the pulse waveforms. Then, a ratio of area (rA) and a
ratio of peak height (rPH) between percussion wave and dicrotic wave as a
function of contact pressure were calculated based on fitted parameters. The
results demonstrated that there was a maximum for waveform peak height, a minimum
for rA (rAmin) and a minimum for rPH (rPHmin) appeared as contact pressure
varied. On average, older patients had higher peak amplitude and a significantly
smaller rAmin (p<0.001) and rPHmin (p<0.02) than the young and old volunteers.
The rAmin and rPHmin calculated with the mathematical model had moderate to
strong positive linear correlations (r=0.66 to 0.84, p<0.006) with those directly
calculated without the model. The receiver operating characteristic (ROC)
analysis showed that the rAmin calculated with the model and the contact pressure
measured at the rAmin had good diagnostic accuracy to distinguish healthy
volunteers vs. diseased patients. Therefore, using the mathematical model to
quantitatively analyze the radial pulse waveforms as a function of contact
pressure could be useful in the diagnosis of cardiovascular diseases.
PMID- 28690045
TI - A FSI computational framework for vascular physiopathology: A novel flow-tissue
multiscale strategy.
AB - A novel fluid-structure computational framework for vascular applications is
herein presented. It is developed by combining the double multi-scale nature of
vascular physiopathology in terms of both tissue properties and blood flow.
Addressing arterial tissues, they are modelled via a nonlinear multiscale
constitutive rationale, based only on parameters having a clear histological and
biochemical meaning. Moreover, blood flow is described by coupling a three
dimensional fluid domain (undergoing physiological inflow conditions) with a zero
dimensional model, which allows to reproduce the influence of the downstream
vasculature, furnishing a realistic description of the outflow proximal pressure.
The fluid-structure interaction is managed through an explicit time-marching
approach, able to accurately describe tissue nonlinearities within each
computational step for the fluid problem. A case study associated to a patient
specific aortic abdominal aneurysmatic geometry is numerically investigated,
highlighting advantages gained from the proposed multiscale strategy, as well as
showing soundness and effectiveness of the established framework for assessing
useful clinical quantities and risk indexes.
PMID- 28690046
TI - Kinematic behavior of a customized surface-guided knee implant during simulated
knee-bending.
AB - Different designs of total knee replacements (TKRs) aim to enhance the
satisfaction of the patients by providing close to normal kinematics. In the
surface-guided TKRs, the guidance of the motion in a normal pattern should be
achieved through specially shaped articulating geometries. This study used
virtual simulation along with a load-controlled knee wear simulator to evaluate
the kinematic performance of a customized surface-guided TKR under weight-bearing
conditions of lunging and squatting activities. The outcome pattern of TKR motion
almost agreed with the predefined design target. The tibial insert rotated
internally through a maximum angle of 10.6 degrees and 19.94 degrees for the
experimentally simulated lunging and squatting cycles, respectively. This
rotation occurred around a medial center, as indicated by a small amount of
posterior translation of the medial condyle (maximum of 2.5mm and 6.4mm for
lunging and squatting) versus the posterior translation of the lateral condyle
(maximum of 12mm and 24.2mm for lunging and squatting). The contact forces mainly
provided the guidance of the motion at the tibiofemoral articulating surfaces.The
normalized root mean square error between outcomes of the virtual simulations and
tests for the angle of internal-external rotation of the tibial insert was less
than 8% for one cycle of lunging and squatting. These measures confirm the
validity of the virtual simulation for future evaluations of the customized
surface-guided TKRs.
PMID- 28690047
TI - Geometry of an inflated membrane in elliptic bulge tests: Evaluation of an
ellipsoidal shape approximation by stereoscopic digital image correlation
measurements.
AB - Elliptic bulge tests are conducted on liver capsule, a fibrous connective
membrane, associated with a field measurement method to assess the global
geometry of the samples during the tests. The experimental set up is derived from
a previous experimental campaign of bulge tests under microscope. Here, a
stereoscopic Digital Image Correlation (DIC) system is used to measure global
parameters on the test and investigate some assumptions made on the testing
conditions which could not been assessed with microscopic measurements. In
particular, the assumption of an ellipsoidal shape of the inflated membrane is
tested by comparing the actual sample shape measured by stereoscopic DIC with an
idealized ellipsoidal shape. Results indicate that a rather constant gap exists
between the idealized and actual position. The approximation in the calculation
of a macroscopic strain through analytical modeling of the test is estimated
here. The study of the liver capsule case shows that important differences can be
observed in strain calculation depending on the method and assumptions taken.
Therefore, analytical modeling of mechanical tests through ellipsoidal
approximation needs to be carefully evaluated in every application. Here the
field measurement allows assessing the validity of these modeling assumptions.
Moreover, it gives precious details about the boundary conditions of the bulge
test and revealed the heterogeneous clamping, highlighted by strain
concentrations.
PMID- 28690048
TI - Defining the factors that affect solute permeation of gap junction channels.
AB - This review focuses on the biophysical properties and structure of the pore and
vestibule of homotypic gap junction channels as they relate to channel
permeability and selectivity. Gap junction channels are unique in their sole role
to connect the cytoplasm of two adjacent cells. In general, these channels are
considered to be poorly selective, possess open probabilities approximating
unity, and exhibit mean open times ranging from milliseconds to seconds. These
properties suggest that such channels can function as delivery pathways from cell
to cell for solutes that are significantly larger than monovalent ions. We have
taken quantitative data from published works concerning unitary conductance, ion
flux, and permeability for homotypic connexin 43 (Cx43), Cx40, Cx26, Cx50, and
Cx37, and performed a comparative analysis of conductance and/or ion/solute flux
versus diffusion coefficient. The analysis of monovalent cation flux portrays the
pore as equivalent to an aqueous space where hydrogen bonding and weak
interactions with binding sites dominate. For larger solutes, size, shape and
charge are also significant components in determining the permeation rate. This
article is part of a Special Issue entitled: Gap Junction Proteins edited by Jean
Claude Herve.
PMID- 28690049
TI - Initial validation of blubber cortisol and progesterone as indicators of stress
response and maturity in an otariid; the California sea lion (Zalophus
californianus).
AB - Chronic stress can have detrimental effects on an individual's health and
reproductive success. The use of cortisol quantification as an indicator of
stress in free-ranging cetaceans and phocids is increasing but no studies have
applied this technique on blubber in otariids. We measured cortisol
concentrations in blubber samples obtained from California sea lions, Zalophus
californianus, stranded in San Diego County and those incidentally killed in the
California drift gillnet fishery. We also measured progesterone concentrations to
assess female reproductive status and, in males, as a potential secondary measure
of adrenal steroid production. Blubber cortisol and progesterone values were
compared across demographic groups (sex and maturity), season, and proportion
blubber lipid extracted. Stranded animals (247.3+/-70.767SEng/gblubber) had
significantly higher cortisol concentrations compared to fishery bycaught (8.1+/
2.108SEng/gblubber) animals. These findings are likely driven by inherent
differences in the cause of death and associated nutritional state coupled with
the mean duration of expiration for these two groups of animals (i.e., the
duration from an animal's initial perception of the threat-to-self until death).
The duration of transition from healthy state to death in stranded animals is on
the order of many hours to weeks while in fishery bycaught animals, this
transition occurs much more rapidly (i.e., seconds to tens of minutes). The
presumed longer duration of the mortality event in stranded animals gives
sufficient time for elevated cortisol to diffuse into the blubber. No significant
differences between demographic groups, or season were found. However, blubber
cortisol declined inversely with proportion blubber lipid extracted, suggesting
utility in assessing long-term nutritional status. Blubber progesterone was
significantly higher in mature females than immature females (153.8+/
54.546SEng/gblubber and 9.7+/-3.60SEng/gblubber respectively), containing on
average 15 times more progesterone, irrespective of pregnancy state.
Additionally, a significant relationship between mean cortisol and progesterone
was found in males with >35% blubber lipid (p<0.0001). This study is an initial
step in validating blubber cortisol and progesterone concentrations as a
potential marker of stress response and reproductive state, respectively, in
otariids. Especially when paired with dart biopsying, this approach could
represent a relatively rapid way to assess baseline stress, nutritional status
and reproductive states in otariids while minimizing the effects of sampling.
PMID- 28690050
TI - Editorial of the International Symposium on Comparative Endocrinology and
Integrative Physiology - CEIP 2015.
PMID- 28690051
TI - Nipple sparing mastectomy for breast cancer is associated with high patient
satisfaction and safe oncological outcomes.
AB - BACKGROUND: The preservation of the nipple areolar complex (NAC) for cancer
treatment is still a matter of debate because of suspected increase of local
recurrence and surgery-specific complications. The aim of the study was to
investigate both the relapse risk associated with nipple sparing mastectomy (NSM)
for breast cancer and women's satisfaction with preservation of the NAC. METHODS:
We included retrospectively all patients who had skin-sparing mastectomy (SSM) or
NSM from 2007 to 2012 for breast cancer or ductal carcinoma in situ (DCIS). We
compared NSM and SSM group for oncological and surgical outcomes. Patients'
satisfaction and quality of life has been evaluated by a specifically designed
questionnaire. RESULTS: We included 63NSM (41.5%) and 89SM (58.5%). Eighty-nine
(58.6%) patients had DCIS, and the other had small invasive disease. Median
follow-up was 42 (IQR: 18-58) months. Local recurrence rate was 1.7% (n=1) in the
NSM group and 0% in the SSM group without recurrence in the preserved nipple.
After NSM, one patient had complete NAC necrosis, and three patients suffered
partial necrosis. Satisfaction with the NAC was higher in the NSM group compared
to the SSM group with delayed reconstruction of the nipple (75% vs. 59%, P=0.14).
Patients with NSM required less psychological support before (P=0.028) and
immediately after surgery (P=0.14) than patients in the SSM group. CONCLUSION:
NSM can successfully and safely be performed for pre-invasive and small invasive
breast cancer. Besides esthetic aspects, preserving the nipple may ease the
acceptance of these radical form of surgery.
PMID- 28690052
TI - Lebetimonas natsushimae sp. nov., a novel strictly anaerobic, moderately
thermophilic chemoautotroph isolated from a deep-sea hydrothermal vent polychaete
nest in the Mid-Okinawa Trough.
AB - A moderately thermophilic, strictly anaerobic, chemoautotrophic bacterium,
designated strain HS1857T, was isolated from a deep-sea hydrothermal vent at the
Noho site in the Mid-Okinawa Trough. Strain HS1857T grew between 35 and 63
degrees C (optimum 55 degrees C), in the presence of 10-55gl-1 NaCl (optimum 25gl
1), and pH 5.5-7.1 (optimum 6.4). Growth occurred with molecular hydrogen as the
electron donor and elemental sulfur, nitrate, or selenate as the electron
acceptors. Formate could serve as an alternative electron donor with nitrate as
an electron acceptor. During growth with nitrate as the electron acceptor, strain
HS1857T produced ammonium and formed a biofilm. CO2 was utilized as the sole
carbon source. The G+C content of the genomic DNA was 33.2mol%. Phylogenetic
analysis of the 16S rRNA gene sequence indicated that strain HS1857T is a member
of the order Nautiliales, showing a sequence similarity of 95.0% with Lebetimonas
acidiphila Pd55T. The fatty acid composition was similar to that of L.
acidiphila, which was dominated by C18:0 (47.0%) and C18:1 (23.7%). Based on the
genomic, chemotaxonomic, phenotypic characteristics, the name Lebetimonas
natsushimae sp. nov., is proposed. The type strain is HS1857T (=NBRC 112478T=DSM
104102T).
PMID- 28690054
TI - Fuzzy Evidential Network and Its Application as Medical Prognosis and Diagnosis
Models.
AB - Uncertainty is one of the important facts of the medical knowledge. Medical
prognosis and diagnosis, as the essential parts of medical knowledge, is affected
by different aspects of uncertainty, which must be managed. In the previous
studies, different theories such as Bayesian probability theory, evidence theory,
and fuzzy set theory have been developed to represent and manage different
aspects of uncertainty. Recently, hybrid frameworks are suggested to deal with
various types of uncertainty in a single framework. Evidential networks are
general frameworks for dealing explicitly with total and partial ignorance and
offer powerful combination rule of contradictory evidence. In this framework, the
fuzziness of linguistic variables is neglected while these variables commonly
appear in the medical domain knowledge and different sources of medical
information. In addition, the evidential network parameters are determined based
on the experts' knowledge and no data-driven algorithm is provided to learn these
parameters. In this study, a novel hybrid framework called fuzzy evidential
network was suggested to manage the imprecision and epistemic uncertainty of
medical prognosis and diagnosis. Also, a data-driven algorithm based on the fuzzy
set theory and the fuzzy maximum likelihood is provided to learn the network
parameters from clinical databases. The performance of the proposed framework as
various prognosis and diagnosis models, compared with well-known machine learning
algorithms and the results showed its superiority. Also, an evidential method is
suggested to handle the missing values and its results were compared with KNN
imputation method.
PMID- 28690055
TI - Antitumor effect of Ferula assa foetida oleo gum resin against breast cancer
induced by 4T1 cells in BALB/c mice.
AB - BACKGROUND: Ferula assa foetida commonly consumed as a healthy beverage has been
demonstrated to have various biological activities, including antioxidation, anti
obesity and anti-cancer. OBJECTIVE: Our study aims to investigate the antitumor
effect of asafoetida in vivo using mouse mammary carcinoma 4T1 cells. MATERIALS
AND METHODS: In the study, female BALB/c mice were divided into two groups (n =
6), which were control (untreated) and other group of mice with breast cancer
treated with 100 mg/kg of asafoetida, respectively, by oral gavage. All mice were
injected into the mammary fat pad with 4T1 cells (1 * 105 4T1 cells/0.1 ml of
phosphate buffer solution). Asafoetida was administered on day 15 after the tumor
had developed for 3 weeks. At end of experiment, tumor weight, tumor volume and
tumor burden were measured and lung, liver, kidney and tumor were harvested and
sections were prepared for histopathological analysis. Lipoxygenase inhibitory
and antioxidant activity of asafoetida was also determined. RESULTS: Our results
showed that treatment with asafoetida was effective in decreasing the tumor
weight and tumor volume in treated mice. Body weight significantly increased in
female BALB/c mice against control. Apart from the antitumor effect, asafoetida
decreased lung, liver and kidney metastasis and also increased areas of necrosis
in the tumor tissue respectively. CONCLUSIONS: The present study demonstrated
that asafoetida has potent antitumor and antimetastasis effects on breast cancer
and is a potential source of natural antitumor products.
PMID- 28690056
TI - Associations between subclinical hypocalcemia and postparturient diseases in
dairy cows.
AB - Dairy cows suffer blood Ca losses as lactation begins and might be affected by
hypocalcemia in its clinical (total serum Ca concentration <1.50 mM) or
subclinical form (total serum Ca concentration <=2.14 mM). Several studies have
suggested that hypocalcemia is associated with different health problems of the
cow but results from different studies are not consistent. The objective of this
study was to assess potential associations between subclinical hypocalcemia
(SCHC) and displaced abomasum, intramammary infections, metritis, retained
placenta, and ketosis. Also, the associations between SCHC and milk yield and
reproductive function were evaluated. After discarding cows (32) with clinical
hypocalcemia, a total of 764 cows from 6 different commercial farms were enrolled
in this study. Blood samples were collected at 24 to 48 h postcalving and
analyzed for total Ca concentration. Odds ratios of the different afflictions
potentially associated with SCHC were calculated. Seventy-eight percent of the
analyzed cows incurred SCHC. The occurrence of displaced abomasum, ketosis,
retained placenta, and metritis was 3.7, 5.5, 3.4, and 4.3 times more likely,
respectively, in cows that had SCHC than in cows with normocalcemia. Furthermore,
the risk of incurring retained placenta or metritis increased in multiparous cows
as serum Ca concentrations decreased compared with that in primiparous cows.
Normocalcemic cows, independent of parity, were more likely to show their first
estrus sooner after calving than SCHC cows, but no correlation was found between
SCHC and other reproductive parameters. Different serum Ca concentration cutoffs
were identified for several postpartum afflictions (<=1.93, <=2.05, <=2.05, and
<=2.10 mM for ketosis, retained placenta, metritis, and displaced abomasum,
respectively). In conclusion, SCHC, defined as serum Ca <=2.14 mM, is a frequent
illness affecting the majority of the dairy cows with important repercussions on
health. However, if SCHC were to be used to predict postpartum disease, different
serum Ca cutoff points are likely to be needed because best predictive cutoff
values varied among postpartum ketosis, displaced abomasum, retained placenta,
and metritis.
PMID- 28690053
TI - Close encounters: Moving along bumps, breaks, and bubbles on expanded
trinucleotide tracts.
AB - Expansion of simple triplet repeats (TNR) underlies more than 30 severe
degenerative diseases. There is a good understanding of the major pathways
generating an expansion, and the associated polymerases that operate during gap
filling synthesis at these "difficult to copy" sequences. However, the mechanism
by which a TNR is repaired depends on the type of lesion, the structural features
imposed by the lesion, the assembled replication/repair complex, and the
polymerase that encounters it. The relationships among these parameters are
exceptionally complex and how they direct pathway choice is poorly understood. In
this review, we consider the properties of polymerases, and how encounters with
GC-rich or abnormal structures might influence polymerase choice and the success
of replication and repair. Insights over the last three years have highlighted
new mechanisms that provide interesting choices to consider in protecting genome
stability.
PMID- 28690057
TI - Effects of depleting ionic strength on 31P nuclear magnetic resonance spectra of
micellar casein during membrane separation and diafiltration of skim milk.
AB - Membrane separation processes used in the concentration and isolation of micellar
casein-based milk proteins from skim milk rely on extensive permeation of its
soluble serum constituents, especially lactose and minerals. Whereas extensive
literature exists on how these processes influence the gross composition of milk
proteins, we have little understanding of the effects of such ionic depletion on
the core structural unit of micellar casein [i.e., the casein phosphate
nanocluster (CPN)]. The 31P nuclear magnetic resonance (NMR) is an analytical
technique that is capable of identifying soluble and organic forms of phosphate
in milk. Thus, our objective was to investigate changes to the 31P NMR spectra of
skim milk during microfiltration (MF) and diafiltration (DF) by tracking
movements in different species of phosphate. In particular, we examined the peak
at 1.11 ppm corresponding to inorganic phosphate in the serum, as well as the low
intensity broad signal between 1.5 and 3.0 ppm attributed to casein-associated
phosphate in the retentate. The MF concentration and DF using water caused a
shift in the relevant 31P NMR peak that could be minimized if orthophosphate was
added to the DF water. However, this did not resolve the simultaneous change in
retentate pH and increased solubilization of micellar casein protein. The
addition of calcium in combination with orthophosphate prevented micellar casein
solubilization and simultaneously contributed to preservation of the CPN
structure, except for overcorrection of retentate pH in the acidic direction. A
more complex DF solution, involving a combination of phosphate, calcium, and
citrate, succeeded in both CPN and micellar casein structure preservation while
maintaining retentate pH in the region of the original milk pH. The combination
of 31P NMR as an analytical technique and experimental probe during MF/DF
processes provided useful insights into changes occurring to CPN while retaining
the micellar state of casein.
PMID- 28690058
TI - Flow cytometric assessment of myeloperoxidase in bovine blood neutrophils and
monocytes.
AB - Myeloperoxidase (MPO) is a lysosomal peroxidase enzyme mainly stored in the
azurophilic granules of neutrophils playing an important role in innate immunity
for first-line protection against microorganisms in many species including
cattle. As such, determination of MPO has become of great interest for the
diagnosis of infectious and inflammatory diseases in multiple species such as
humans. In cattle, MPO determination is rarely done because methods to assess MPO
in this species are limited: functional assays have been described earlier, but
so far, the quantification of MPO at the single cell level has not been done yet.
In the present paper, an innovative flow cytometric method to assess MPO in blood
leukocytes of dairy cattle is described. A commercial anti-bovine MPO was used
following density gradient separation to isolate polymorphonuclear (PMN) and
mononuclear (MN) leukocytes from blood. Identification of PMN and MN, subdivided
in monocytes and lymphocytes, was based on the expression of the surface markers
CH138A and CD172A. The optimized protocol was subsequently evaluated on blood
samples of 17 Holstein Friesian heifers. Myeloperoxidase expression was measured
flow cytometrically and visualized by fluorescence microscopic imaging of sorted
PMN and MN populations. We suggest this innovative method to be useful in the
field for early detection of cows at higher risk for inflammatory diseases such
as mastitis and metritis during the transition period.
PMID- 28690059
TI - The relationship between Norwegian Red heifer growth and their first-lactation
test-day milk yield: A field study.
AB - Today's Norwegian Red (NR) is markedly different from the one that existed 25 yr
ago due to the continuous genetic improvement of economically important traits.
Still, current national recommendations on replacement heifer rearing largely are
based on results from Danish studies from the late 1980s to the mid 1990s. The
objectives of the present study were to gain information on (1) growth and growth
profiles of modern NR replacement heifers in commercial dairy herds and (2) how
growth during the rearing period affects the heifers' milk yield during their
first lactation. To this end, we conducted a field study on 5 high-producing and
5 low-producing commercial dairy farms from each of 3 geographical regions in
Norway. On these 30 farms, we combined repeated onsite registrations of growth on
all available females from newborn to calving with registrations deriving from
the Norwegian Dairy Herd Recording System. Each herd was visited 6 to 8 times
over a period of 2 yr. At each visit, heart girth circumference on all available
young females was measured. Registrations were made on a total of 3,110 heifers.
After imposing restrictions on the data, growth parameters were estimated based
on information from 536 animals, whereas 350 of these animals had the required
information needed to estimate the relationship between growth and test-day milk
yield. Our findings pointed toward an optimal ADG of 830 g/d from 10 to 15 mo of
age that would optimize first-lactation yield of heifers in an average Norwegian
dairy herd. The optimum will likely increase from selection over time. Utilizing
simple proportionality, the ADG between 5 and 10 mo of age ideally should be 879
g/d, taking into account the fact that animal growth rate is higher at low ages
and that a high prepubertal growth rate had no negative effect on first-lactation
yield. When such a rearing practice is used to meet the requirements of today's
genetically improved NR heifer, heifers can both optimize production in their
first lactation and enter the milking herd earlier than the current average age
of 24.8 mo.
PMID- 28690060
TI - Genetically modified Lactococcus lactis producing a green fluorescent protein
bovine lactoferrin fusion protein suppresses proinflammatory cytokine expression
in lipopolysaccharide-stimulated RAW 264.7 cells.
AB - Lactoferrin (LF), an iron-binding glycoprotein distributed widely in the
biological fluids of mammals, is believed to play an important role in host
defenses against infection. Previous studies in animal models and humans
demonstrated that combined administration of LF and probiotic lactic acid
bacteria (LAB) can prevent sepsis. In this study, we genetically engineered a
probiotic LAB strain, Lactococcus lactis, to produce recombinant bovine LF based
on the green fluorescent protein (GFP)-fused expression system. Western blotting
confirmed that the genetically modified L. lactis strain (designated NZ-GFP-bLF)
produced a protein corresponding to a fusion of GFP and bLF in the presence of
nisin, an inducer of target gene expression. The protein synthesized by NZ-GFP
bLF was fluorescent and thus we monitored the time-dependent change in the
production level of the recombinant protein using fluorometric analysis. The
utility of NZ-GFP-bLF in preventing sepsis was determined by investigating its
anti-inflammatory property in lipopolysaccharide (LPS)-stimulated mouse
macrophage RAW 264.7 cells. Pretreatment of RAW 264.7 cells with NZ-GFP-bLF
significantly attenuated the LPS-induced mRNA expression and protein production
of 3 proinflammatory cytokines (IL-1alpha, IL-6, and tumor necrosis factor-alpha)
compared with pretreatment with a vector control strain of L. lactis. Our results
suggest that NZ-GFP-bLF holds promise for the development of a new prophylaxis
for sepsis.
PMID- 28690061
TI - Bovine miR-146a regulates inflammatory cytokines of bovine mammary epithelial
cells via targeting the TRAF6 gene.
AB - It has been reported previously that bovine miR-146a (bta-miR-146a) is
significantly differentially expressed in mammary glands infected with mastitis,
compared with healthy udders. This suggests that bta-miR-146a plays an important
role in the regulation of mammary inflammation. However, the specifics of this
function have yet to be elucidated. Bovine mammary epithelial cells (bMEC)
represent the first line of defense against pathogens and have important roles in
initiating and regulating inflammatory responses and innate immunity during
infection. In this study, a double luciferase reporter assay was used to confirm
that bta-miR-146a directly targets the 3' UTR of the tumor-necrosis factor
receptor-associated factor 6 (TRAF6) gene. To elucidate the role of bta-miR-146a
in innate immune responses, either a mimic or inhibitor of bta-miR-146a was
transfected into bMEC stimulated with lipopolysaccharide, which activates the
innate immune response through the toll-like receptor (TLR) 4/nuclear factor (NF)
kappaB signaling pathway. Forty-eight hours posttransfection, quantitative real
time PCR and Western blots were used to detect the expressions of the related
genes and proteins, respectively. An ELISA was used to measure the quantity of
inflammatory factors in culture supernatants. The results showed that bta-miR
146a significantly inhibits both mRNA and protein expression levels of bovine
TRAF6, and ultimately suppresses downstream expression of NF-kappaB mRNA and
protein. As a result, production of NF-kappaB-dependent inflammatory mediators
such as tumor necrosis factor alpha, IL-6, and IL-8 are suppressed following
lipopolysaccharide stimulation of bMEC. Thus, we concluded that bta-miR-146a acts
as a negative feedback regulator of bovine inflammation and innate immunity
through downregulation of the TLR4/TRAF6/NF-kappaB pathway. This study presents a
potential regulatory mechanism of bta-miR-146a on immune responses in bovine
mammary infection and may provide a potential therapeutic target for mastitis.
PMID- 28690062
TI - Technical note: Nontargeted detection of adulterated plant proteins in raw milk
by UPLC-quadrupole time-of-flight mass spectrometric proteomics combined with
chemometrics.
AB - We built and validated a chemometric model to detect possible milk adulteration
with plant proteins. Specifically, we extracted proteins in raw milk, treated
with tryptic digestion, and obtained peptide fingerprints by UPLC-quadrupole time
of-flight-mass spectrometry with proteomics to differentiate authentic milks from
their counterparts adulterated with nonmilk proteins. This approach is able to
detect soybean and pea powder-adulterated milks at as low as 1% (wt/wt).
Additionally, we obtained the characteristic peptide sequences for milk
authentication by principal component analysis. The prediction accuracies for
milk authentication by partial least-squares-discriminant analysis were greater
than 95%. These results indicated that peptide fingerprints with the chemometric
analysis could be successfully applied for milk quality control.
PMID- 28690063
TI - Influence of food deprivation on intravenous glucose tolerance test traits in
Holstein Friesian heifers.
AB - Glucose is essential for numerous cellular functions due to its involvement in
energy supply from early development to adulthood. In the lactating cow, glucose
demands by the mammary gland significantly increase to support milk production
when compared with other tissues. Thus, insufficient blood glucose levels might
predispose dairy cows to metabolic disturbances. The intravenous glucose
tolerance test (ivGTT) is a suitable tool to characterize glucose metabolism and
insulin responses, but results must be reliable and repeatable. One factor
influencing ivGTT is food deprivation period, which has been considered as an
obligatory requirement before conduction of glucose tolerance studies in
monogastric species, whereas it has been permissive in ruminants. The objective
of this study was to determine the influence of 5 fasting periods (0, 12, 24, 36,
and 48 h) on ivGTT traits and insulin responses in German Holstein heifers. A
total of 140 tests were conducted in 28 females aged 12 to 19 mo. Blood samples
were collected every 7 min within 1 h. Assessed glucose and insulin parameters
included basal serum glucose and insulin concentration, maximum glucose and
insulin concentration obtained between min 7 to 21, and concentrations at min 63
(last sampling) relative to glucose administration, glucose area equivalent (GA),
glucose area under the curve (GAUC), insulin area equivalent (InsA), insulin area
under the curve (InsAUC), and blood glucose half-life time (GHLT). Serum glucose
and insulin concentration were measured according to the hexokinase colorimetric
method and solid phase radio immunoassay, respectively. The generalized linear
mixed model was used to test for significant differences in all glucose traits
and insulin responses at different fasting periods. The model used season and
weight as confounding variables. Glucose and insulin concentrations at 0, 7 to 21
(maximum concentration), and 63 min were affected by the duration of food
deprivation. The GA, InsA, GAUC, InsAUC, and especially GHLT were also affected
by fasting period. A positive linear relationship between GHLT and length of food
deprivation was found. Significantly higher GA, GAUC, GHLT values, and glucose
and insulin concentration at min 63 were obtained at increasing fasting periods.
High intraclass correlation coefficient (0.48) was found for GHLT. The results
demonstrate that GHLT might be used to reliably characterize an individual's
glucose metabolism and the importance of standardizing food deprivation schedules
when performing an ivGTT in nongestating Holstein heifers.
PMID- 28690064
TI - Genetic line comparisons and genetic parameters for endoparasite infections and
test-day milk production traits.
AB - Keeping dairy cows in grassland systems relies on detailed analyses of genetic
resistance against endoparasite infections, including between- and within-breed
genetic evaluations. The objectives of this study were (1) to compare different
Black and White dairy cattle selection lines for endoparasite infections and (2)
the estimation of genetic (co)variance components for endoparasite and test-day
milk production traits within the Black and White cattle population. A total of
2,006 fecal samples were taken during 2 farm visits in summer and autumn 2015
from 1,166 cows kept in 17 small- and medium-scale organic and conventional
German grassland farms. Fecal egg counts were determined for gastrointestinal
nematodes (FEC-GIN) and flukes (FEC-FLU), and fecal larvae counts for the bovine
lungworm Dictyocaulus viviparus (FLC-DV). The lowest values for gastrointestinal
nematode infections were identified for genetic lines adopted to pasture-based
production systems, especially selection lines from New Zealand. Heritabilities
were low for FEC-GIN (0.05-0.06 +/- 0.04) and FLC-DV (0.05 +/- 0.04), but
moderate for FEC-FLU (0.33 +/- 0.06). Almost identical heritabilities were
estimated for different endoparasite trait transformations (log-transformation,
square root). The genetic correlation between FEC-GIN and FLC-DV was 1.00 +/-
0.60, slightly negative between FEC-GIN and FEC-FLU (-0.10 +/- 0.27), and close
to zero between FLC-DV and FEC-FLU (0.03 +/- 0.30). Random regression test-day
models on a continuous time scale [days in milk (DIM)] were applied to estimate
genetic relationships between endoparasite and longitudinal test-day production
traits. Genetic correlations were negative between FEC-GIN and milk yield (MY)
until DIM 85, and between FEC-FLU and MY until DIM 215. Genetic correlations
between FLC-DV and MY were negative throughout lactation, indicating improved
disease resistance for high-productivity cows. Genetic relationships between FEC
GIN and FEC-FLU with milk protein content were negative for all DIM. Apart from
the very early and very late lactation stage, genetic correlations between FEC
GIN and milk fat content were negative, whereas they were positive for FEC-FLU.
Genetic correlations between FEC-GIN and somatic cell score were positive,
indicating similar genetic mechanisms for susceptibility to udder and
endoparasite infections. The moderate heritabilities for FEC-FLU suggest
inclusion of FEC-FLU into overall organic dairy cattle breeding goals to achieve
long-term selection response for disease resistance.
PMID- 28690065
TI - Effects of replacing maize silage with lucerne silage and lucerne silage chop
length on rumen function and milk fatty acid composition.
AB - The objective of this study was to investigate whether higher lucerne (Medicago
sativa; alfalfa) silage inclusion rate and longer lucerne chop length improves
rumen function through increased provision of physically effective fiber, when
included in a maize and lucerne silage-based total mixed ration. Diets were
formulated to contain a 50:50 forage:concentrate ratio [dry matter (DM) basis]
and be isonitrogenous and contain equal levels of neutral detergent fiber (320
g/kg). The forage portion of the offered diets was composed of maize and lucerne
silage DM in proportions (wt/wt) of either 25:75 (high lucerne; HL) or 75:25 (low
lucerne; LL). Second-cut lucerne was harvested and conserved as silage at either
a long (L) or a short (S) chop length (geometric mean particle lengths of 9.0 and
14.3 mm, respectively). These variables were combined in a 2 * 2 factorial
arrangement to give 4 treatments (HLL, HLS, LLL, LLS), which were fed in a 4 * 4
Latin square design study to 4 rumen-cannulated, multiparous, Holstein dairy cows
in mid lactation. Effects on DM intake, chewing behavior, rumen volatile fatty
acid concentration, rumen pH, rumen and fecal particle size, milk production, and
milk fatty acid profile were measured. Longer chop length increased rumination
times per kilogram of DM intake (+2.8 min/kg) relative to the S chop length, with
HLL diets resulting in the most rumination chews. Rumen concentrations of total
volatile fatty acids, acetate, and n-valerate were higher for the HLS diet than
the other 3 diets, whereas rumen propionate concentration was lowest for the HLL
diet. Physically effective fiber (particles >4 mm) percentage in the rumen mat
was increased when L chop length was fed regardless of lucerne inclusion rate. No
effect of treatment was observed for milk yield, although milk protein
concentration was increased by L for the LL diet (+1.6 g/kg) and decreased by L
for the HLL diet (-1.4 g/kg). Milk fat concentrations of total cis-18:1 (+3.7
g/100 g of fatty acids) and 18:3 n-3 (+0.2 g/100 g of fatty acids) were greater
with HL. In conclusion, longer lucerne silage chop length increased time spent
ruminating per kilogram of DM intake, but had no effect on rumen pH in the
present study. Increasing dietary lucerne inclusion rate had no effects on
rumination activity or rumen pH, but decreased the ratio of n-6:n-3
polyunsaturated fatty acid concentrations in milk fat.
PMID- 28690066
TI - Experimental evidence for previously unclassified calcium phosphate structures in
the casein micelle.
AB - 1H-31P Cross-polarization magic angle spinning (CP-MAS) measurements of 40-d-old
Mozzarella cheese and 20 mM EDTA-treated casein micelles revealed that each
sample had immobile phosphorus with the same spectral pattern, which did not
match that of native casein micelles. To identify the immobile phosphorus bodies,
1H-31P CP-MAS spectra and cross-polarization kinetics measurements were
undertaken on native casein micelles, EDTA-chelated casein micelles, and
reference samples of beta-casein and hydroxyapatite. The results showed that the
immobile phosphorus bodies in the mature Mozzarella cheese had the following
characteristics: they are immobile phosphoserine residues (not colloidal calcium
phosphate); they are not the product of phosphoserine to colloidal calcium
phosphate bridging; the phosphate is complexed to calcium; their rigidity is
localized to a phosphorus site; their rigidity and bond coupling is unaffected by
protein hydration; and the immobile bodies share a narrow range of bond
orientations. Combining these observations, the best explanation of the immobile
phosphorus bodies is that bonding structures of phosphorus-containing groups and
calcium exist within the casein micelle that are not yet clearly classified in
the literature. The best candidate is a calcium-bridged phosphoserine-to
phosphoserine linkage, either intra- or inter-protein.
PMID- 28690067
TI - Transient changes in milk production efficiency and bacterial community
composition resulting from near-total exchange of ruminal contents between high-
and low-efficiency Holstein cows.
AB - The objectives of this study were to determine if milk production efficiency
(MPE) is altered by near-total exchange of ruminal contents between high- (HE)
and low-MPE (LE) cows and to characterize ruminal bacterial community composition
(BCC) before exchange and over time postexchange. Three pairs of ruminally
cannulated, third-lactation cows were selected whose MPE (energy-corrected milk
per unit of dry matter intake) differed over their first 2 lactations.
Approximately 95% of ruminal contents were exchanged between cows within each
pair. Ruminal pH and volatile fatty acid (VFA) profiles, along with BCC
(characterized by sequencing of the variable 4 region of 16S rRNA genes), were
assessed just before feeding on d -8, -7, -5, -4, -1, 1, 2, 3, 7, 10, 14, 21, 28,
35, 42, and 56, relative to the exchange date. High-MPE cows had higher total
ruminal VFA concentrations, higher molar percentages of propionate and valerate,
and lower molar percentages of acetate and butyrate than did LE cows, and re
established these differences 1 d after contents exchange. Across all LE cows,
MPE increased during 7 d postexchange but declined thereafter. Two of the 3 HE
cows displayed decreases in MPE following introduction of the ruminal contents
from the corresponding LE cow, but MPE increased in the third HE cow, which was
determined to be an outlier. For all 6 cows, both liquid- and solids-associated
BCC differed between individuals within a pair before contents exchange. Upon
exchange, BCC of both phases in all 3 pairs was more similar to that of the donor
inoculum than to preexchange host BCC. For 5 of 6 cows, the solids-associated
community returned within 10 d to more resemble the preexchange community of that
host than that of the donor community. Individual variability before the exchange
was greater in liquids than in solids, as was the variability in response of
bacterial communities to the exchange. Individual cows varied in their response,
but generally moved toward re-establishment of their preexchange communities by
10 d after contents exchange. By contrast, ruminal pH and VFA profiles returned
to preexchange levels within 1 d. Despite the small number of cows studied, the
data suggest an apparent role for the ruminal bacterial community as a
determinant of MPE.
PMID- 28690068
TI - Effects of feeding alfalfa stemlage or wheat straw for dietary energy dilution on
nutrient intake and digestibility, growth performance, and feeding behavior of
Holstein dairy heifers.
AB - Feeding high-quality forage diets may lead to excessive weight gains and over
conditioning for dairy heifers. Restriction of energy density and dry matter
intake by using low-energy forages, such as straw, is a good approach for
controlling this problem. Alfalfa stems contain high fiber and moderate protein
content and have the potential to be used to replace straw to reduce dietary
energy. The objective of this study was to compare nutrient intakes,
digestibilities, growth performance, and feeding behaviors of dairy heifers
offered an alfalfa silage/corn silage high-energy diet (HE; 13.1% crude protein,
65.4% total digestible nutrients, 39.7% neutral detergent fiber) with 2 energy
diluted diets that replaced various proportions of the corn or alfalfa silages
with either alfalfa stemlage (STM; 12.6% crude protein, 59.1% total digestible
nutrients, 46.4% neutral detergent fiber) or chopped wheat straw (WS; 12.6% crude
protein, 61.9% total digestible nutrients, 43.7% neutral detergent fiber).
Seventy-two pregnant Holstein heifers (16.8 +/- 1.3 mo) were stratified into 3
blocks (24 heifers/block) by initial body weight (light, 440 +/- 18.0 kg; medium,
486 +/- 18.6 kg; heavy, 534 +/- 25.1 kg), with each block composed of 3 pens (8
heifers/pen), with diets assigned randomly to 1 pen within the block. Diets were
offered in a 56-d feeding trial. Both dry matter intake and energy intake were
decreased with the addition of low-energy forages to the diets, but no
differences in dry matter intake were observed across diluted diets.
Digestibility of dry matter, organic matter, neutral detergent fiber, and
apparent N were greater for HE compared with diluted diets, and for WS compared
with STM. Total body weight gain (74 vs. 56 kg) and average daily gain (1.32 vs.
1.00 kg/d) were greater for heifers offered HE compared with diluted diets. Feed
efficiency tended to be less for heifers offered the diluted diets compared with
HE (10.7 vs. 8.6 kg of feed/kg of gain). Heifers did not sort for or against
particles when offered HE. However, increased sorting behavior was observed for
diluted diets. Compared with ad libitum feeding dairy heifers a diet with high
nutrient content forages (corn silage and alfalfa silage), use of diet diluted
with alfalfa stemlage or wheat straw is an effective feeding management strategy
to control total daily dry matter and energy intake by increasing gut fill, and
maintain desirable body condition and growth rates, even though the diluted diets
had greater sortability.
PMID- 28690069
TI - Bovine leukemia virus G4 enhances virus production.
AB - The nonstructural G4 gene of bovine leukemia virus (BLV) has been thought to
function in virus replication. However, the discovery of the AS1 gene on the
antisense strand of the G4 gene has affected this interpretation. In this study,
we investigated the function of G4 in virus production independent of the AS1
gene using a reverse genetic approach, and briefly examined the association of
the G4 protein with Tax, which is also a nonstructural protein that promotes
virus replication. First, we constructed a mutant molecular clone of BLV with a
nonsense mutation in G4 that had a minimal effect on the AS1 gene. Comparison of
the wild-type and mutant molecular clones indicated that the nonsense mutation
resulted in a reduction of virus in the culture supernatant and accumulation of
viral RNA (vRNA) in cells. Moreover, G4 and Tax expression in cells was shown to
synergistically enhance virus production. Therefore, we suggest that G4 enhances
virus production through abrogation of vRNA accumulation.
PMID- 28690070
TI - Plant viruses and viroids in the United Kingdom: An analysis of first detections
and novel discoveries from 1980 to 2014.
AB - This review covers 35 years (1980-2014) representing a period of changing land
use and agricultural practices in the United Kingdom (UK), which have also
witnessed a marked change in the availability and application of new diagnostic
technologies. During this period there have been 53 first records of viruses and
viroids, of which 36 were first UK findings and a further 17 previously
undescribed viruses. Given the challenges in detection and diagnosis of plant
viruses, the field of plant virology has been an early adopter of new diagnostic
technologies and these data highlight the transition from a reliance on
biological, morphological, and serological based identification to the increased
application of nucleic acid based detection methods and latterly the emergence of
Next-Generation Sequencing. This review presents a comprehensive record of these
findings and an analysis of how the potential drivers of change such as commodity
based research, trade, as well as the application of diagnostic technology, could
have influenced the frequency and type of findings.
PMID- 28690071
TI - Plasmodium vivax rhomboid-like protease 1 gene diversity in Thailand.
AB - BACKGROUND: Plasmodium vivax infection remains a major public health problem,
especially along the Thailand border regions. We examined the genetic diversity
of this parasite by analyzing single-nucleotide polymorphisms (SNPs) of the P.
vivax rhomboid-like protease 1 gene (Pvrom1) in parasites collected from western
(Tak province, Thai-Myanmar border) and eastern (Chanthaburi province, Thai
Cambodia border) regions. METHODS: Data were collected by a cross-sectional
survey, consisting of 47 and 45 P. vivax-infected filter paper-spotted blood
samples from the western and eastern regions of Thailand, respectively during
September 2013 to May 2014. Extracted DNA was examined for presence of P. vivax
using Plasmodium species-specific nested PCR. Pvrom1 gene was PCR amplified,
sequenced and the SNP diversity was analyzed using F-STAT, DnaSP, MEGA and LIAN
programs. RESULTS: Comparison of sequences of the 92 Pvrom1 831-base open reading
frames with that of a reference sequence (GenBank acc. no. XM001615211) revealed
17 samples with a total of 8 polymorphic sites, consisting of singleton (exon 3,
nt 645) and parsimony informative (exon 1, nt 22 and 39; exon 3, nt 336, 537 and
656; and exon 4, nt 719 and 748) sites, which resulted in six different deduced
Pvrom1 variants. Non-synonymous to synonymous substitutions ratio estimated by
the DnaSP program was 1.65 indicating positive selection, but the Z-tests of
selection showed no significant deviations from neutrality for Pvrom1 samples
from western region of Thailand. In addition McDonald Kreitman test (MK) showed
not significant, and Fst values are not different between the two regions and the
regions combined. Interestingly, only Pvrom1 exon 2 was the most conserved
sequences among the four exons. CONCLUSIONS: The relatively high degree of Pvrom1
polymorphism suggests that the protein is important for parasite survival in face
of changes in both insect vector and human populations. These polymorphisms could
serve as a sensitive marker for studying plasmodial genetic diversity. The
significance of Pvrom1 conserved exon 2 sequence remains to be investigated.
PMID- 28690073
TI - Demonstrating Hickam's Dictum: Metachronous Pulmonary Adenocarcinoma, Carcinoid
Tumor, and Histoplasmosis.
PMID- 28690074
TI - Three Thrombi at Onset: Behcet's Disease.
PMID- 28690072
TI - Identity of Gli1+ cells in the bone marrow.
AB - Bone marrow fibrosis is a critical component of primary myelofibrosis in which
normal bone marrow tissue and blood-forming cells are gradually replaced with
scar tissue. The specific cellular and molecular mechanisms that cause bone
marrow fibrosis are not understood. A recent study using state-of-the-art
techniques, including in vivo lineage tracing, provides evidence that Gli1+ cells
are the cells responsible for fibrotic disease in the bone marrow. Strikingly,
genetic depletion of Gli1+ cells rescues bone marrow failure and abolishes
myelofibrosis. This work introduces a new central cellular target for bone marrow
fibrosis. The knowledge that emerges from this research will be important for the
treatment of several malignant and nonmalignant disorders.
PMID- 28690075
TI - Tumor microenvironment changes leading to resistance of immune checkpoint
inhibitors in metastatic melanoma and strategies to overcome resistance.
AB - Immunotherapy with checkpoint inhibitors targeting CTLA-4 and/or PD-1 receptors
independent of the BRAF mutational status and targeted therapy with BRAF and MEK
inhibitors in BRAF V600 mutated patients have taken the forefront of advanced
melanoma treatment. The main advantage of immunotherapy is its ability to provide
durable responses in a subset of patients. However, significant proportions of
patients either do not respond or have progression after initial response to
immunotherapies. Multiple changes in the tumor microenvironment, such as down
regulation of immune checkpoint ligands by tumor, alteration in interferon
signaling, and activation of alternate immune suppressive pathways, have been
identified as possible reasons for failure of immune checkpoint therapy. Here, we
review the resistance mechanisms adopted by cancer cells to checkpoint inhibitor
therapy and targeted therapy. In addition, we focus on the available and emerging
evidence on tumor microenvironment modulation by BRAF/MEK inhibitor therapy and
its role in improving responses to checkpoint inhibitor therapy.
PMID- 28690076
TI - Patient Nonadherence to Guideline-Recommended Care in Acute Low Back Pain.
AB - OBJECTIVE: To describe the magnitude of patient-reported nonadherence with
guideline-recommended care for acute low back pain. DESIGN: Secondary analysis of
data from participants enrolled in the Paracetamol for Acute Low Back Pain study
trial, a randomized controlled trial evaluating the effectiveness of paracetamol
for acute low back pain. SETTING: Primary care, general practitioner.
PARTICIPANTS: Data from participants with acute low back pain (N=1643).
INTERVENTIONS: Guideline-recommended care, including reassurance, simple
analgesia, and the advice to stay active and avoid bed rest. Also, advice against
additional treatments and referral for imaging. MAIN OUTCOME MEASURES: Proportion
of nonadherence with guideline-recommended care. Nonadherence was defined as (1)
failure to consume the advised paracetamol dose, or (2) receipt of additional
health care, tests, or medication during the trial treatment period (4wk).
Multivariable logistic regression analysis was performed to determine the factors
associated with nonadherence. RESULTS: In the first week of treatment, 39.7% of
participants were classified as nonadherent. Over the 4-week treatment period,
70.0% were nonadherent, and 57.5% did not complete the advised paracetamol
regimen. Higher perceived risk of persistent pain, lower level of disability, and
not claiming workers' compensation were associated with nonadherence, with odds
ratios ranging from .46 to 1.05. CONCLUSIONS: Adherence to guideline-recommended
care for acute low back pain was poor. Most participants do not complete the
advised paracetamol regimen. Higher perceived risk of persistence of complaints,
lower baseline disability, and participants not claiming workers' compensation
were independently associated with nonadherence.
PMID- 28690077
TI - Evidence for Dry Needling in the Management of Myofascial Trigger Points
Associated With Low Back Pain: A Systematic Review and Meta-Analysis.
AB - OBJECTIVE: To evaluate the current evidence of the effectiveness of dry needling
of myofascial trigger points (MTrPs) associated with low back pain (LBP). DATA
SOURCES: PubMed, Ovid, EBSCO, ScienceDirect, Web of Science, Cochrane Library,
CINAHL, and China National Knowledge Infrastructure databases were searched until
January 2017. STUDY SELECTION: Randomized controlled trials (RCTs) that used dry
needling as the main treatment and included participants diagnosed with LBP with
the presence of MTrPs were included. DATA EXTRACTION: Two reviewers independently
screened articles, scored methodologic quality, and extracted data. The primary
outcomes were pain intensity and functional disability at postintervention and
follow-up. DATA SYNTHESIS: A total of 11 RCTs involving 802 patients were
included in the meta-analysis. Results suggested that compared with other
treatments, dry needling of MTrPs was more effective in alleviating the intensity
of LBP (standardized mean difference [SMD], -1.06; 95% confidence interval [CI],
1.77 to -0.36; P=.003) and functional disability (SMD, -0.76; 95% CI, -1.46 to
0.06; P=.03); however, the significant effects of dry needling plus other
treatments on pain intensity could be superior to dry needling alone for LBP at
postintervention (SMD, 0.83; 95% CI, 0.55-1.11; P<.00001). CONCLUSIONS: Moderate
evidence showed that dry needling of MTrPs, especially if associated with other
therapies, could be recommended to relieve the intensity of LBP at
postintervention; however, the clinical superiority of dry needling in improving
functional disability and its follow-up effects still remains unclear.
PMID- 28690078
TI - Continuous Flash Suppression: Stimulus Fractionation rather than Integration.
AB - Recent studies using continuous flash suppression suggest that invisible stimuli
are processed as integrated, semantic entities. We challenge the viability of
this account, given recent findings on the neural basis of interocular
suppression and replication failures of high-profile CFS studies. We conclude
that CFS reveals stimulus fractionation in visual cortex.
PMID- 28690079
TI - [Differentiated penile intra-epithelial neoplasia].
PMID- 28690080
TI - Prolonged TTM - enhanced hypocoagulation and bleeding?
PMID- 28690081
TI - Towards a more continuous evidence evaluation: A collaborative approach to review
the resuscitation science.
PMID- 28690082
TI - Regulation and functions of inflammasome-mediated cytokines in Helicobacter
pylori infection.
AB - Persistent stomach infection with Helicobacter pylori causes chronic mucosal
inflammation (gastritis), which is widely recognized as an essential precursor to
gastric cancer. The IL-1 interleukin family cytokines IL-1beta and IL-18 have
emerged as central mediators of mucosal inflammation. Here, we review the
regulation and functions of these cytokines in H. pylori-induced inflammation and
carcinogenesis.
PMID- 28690083
TI - Analgesic effects of preinjection low-level laser/light therapy (LLLT) before
third molar surgery: a double-blind randomized controlled trial.
AB - OBJECTIVE: The aim of this study was to evaluate the analgesic effects of low
level laser therapy (LLLT) on preinjection sites in patients scheduled for third
molar removal. STUDY DESIGN: This double-blind randomized controlled trial
included 163 healthy patients undergoing third molar extractions. The study
participants were randomly divided into an LLLT and a placebo group. Objective
and subjective data sets were obtained from physiologic feedback (heart rate and
sweat response) and a questionnaire, respectively. In the LLLT group, each
targeted injection site was irradiated twice with 198 mW continuous wave for 30
seconds with a 0.088 cm2 focal spot at an applied energy of 5.94 J and fluence of
67.50 J/cm2. Measurements were recorded from 4 time-points during data
acquisition. RESULTS: There was no significant difference between the LLLT and
placebo groups in pain experience scores associated with the injected sites for
maxillary or mandibular third molar extractions. Mean heart rates before and
during injection were lower in the LLLT group than in the placebo group for both
maxillary and mandibular regions. No statistically significant differences were
observed for any remaining parameters. CONCLUSIONS: The present data indicated
that preinjection LLLT did not effectively decrease the pain felt during local
anesthetic injections before third molar surgery.
PMID- 28690084
TI - Regeneration of gingival tissue using in situ tissue engineering with collagen
scaffold.
AB - OBJECTIVE: The aim of the study was to evaluate 2 types of collagen scaffold for
gingival regeneration. STUDY DESIGN: Two types of collagen scaffolds, CS-pH7.4
and CS-pH3.0, were prepared by processing atelocollagen at pH 7.4 or 3.0,
respectively, followed by dehydrothermal treatment. Gingival wounds with sizes of
4 * 6 mm (rectangle) or 6 mm diameter (circle) were made with buccal incisions in
beagle dogs. The defective area was surgically covered with the CS-pH7.4, CS
pH3.0, or no scaffold (control). Gingival regeneration was assessed by monitoring
the differences in the lengths of the epithelial and submucosal tissues at the
wound site and the normal site. Histopathologic assessments were performed by 4
evaluators independently; statistical significance was evaluated by using the
Wald test. RESULTS: Significantly higher recovery of epithelial and submucosal
tissues, which, in turn, resulted in recovery of gum thickness, was observed in
gingival wounds treated with the CS-pH7.4 compared with that in the control. CS
pH3.0 treatment also resulted in higher gingival regeneration compared with the
control; however, the effects were more pronounced in wounds treated with the CS
pH7.4. CS-pH7.4-treated wounds showed better gingival regeneration compared with
the control and CS-pH3.0-treated wounds, even after adjusting for interevaluator
differences using a linear mixed model. CONCLUSIONS: CS-pH7.4 is a promising
scaffold for gingival tissue regeneration.
PMID- 28690085
TI - Comparison of cone beam computed tomography and digital intraoral radiography
performance in the detection of artificially induced recurrent caries-like
lesions.
AB - OBJECTIVES: The aim of this study was to compare the performance of cone beam
computed tomography (CBCT) and digital radiography in the detection of artificial
recurrent caries-like lesions under amalgam and composite fillings. STUDY DESIGN:
The study included class II cavities in 30 molars that had been filled with
amalgam. Fifteen of those molars had the restoration-enamel interface
artificially demineralized. Phantoms were prepared, and CBCT images were acquired
with 2 units in 3 voxel sizes (K9000, 0.076 mm; i-CAT, 0.2 mm and 0.4 mm).
Intraoral radiographs were obtained with 3 systems (Digora, VistaScan, and RVG
6100). Amalgam fillings were then replaced by composite, and new images were
obtained. Three examiners assessed all of the images. Sensitivity, specificity,
accuracy, and receiver operating characteristic curve were calculated and
verified through analysis of variance and the Tukey test. RESULTS: There were no
significant differences in sensitivity and specificity when the same restorative
material was present or when the restorative materials were compared with the
imaging technique as a constant. As for accuracy and receiver operating
characteristic curve, there were statistically significant differences when the 2
materials were compared, and there were differences in the amalgam group when the
imaging modalities were compared. CONCLUSIONS: CBCT performed similarly to
intraoral radiography in detecting demineralization under restorations. However,
the voxel size and the type of restorative material influenced its performance.
PMID- 28690086
TI - Combined MitraClip implantation and left atrial appendage occlusion - "because
it's there" revisited?
PMID- 28690087
TI - An exo probe-based recombinase polymerase amplification assay for the rapid
detection of porcine parvovirus.
AB - Recombinase polymerase amplification (RPA), an isothermal amplification
technology, has been developed as an alternative to PCR in pathogen detection. A
real-time RPA assay (rt-RPA) was developed to detect the porcine parvovirus (PPV)
using primers and exo probe specific for the VP2 gene. The amplification was
performed at 39 degrees C for 20min. There was no cross-reaction with other
pathogens tested. Using the recombinant plasmid pPPV-VP2 as template, the
analytical sensitivity was 103 copies. The assay performance was evaluated by
testing 115 field samples by rt-RPA and a real-time PCR assay. The diagnostic
agreement between assays was 100%, and PPV DNA was detected in 94 samples. The R2
value of rt-RPA and real-time PCR was 0.909 by linear regression analysis. The
developed rt-RPA assay provides a useful alternative tool for rapid, simple and
reliable detection of PPV in diagnostic laboratories and at point-of-care,
especially in remote and rural areas.
PMID- 28690089
TI - [Diffuse cutaneous abnormality].
PMID- 28690088
TI - A cluster-randomized trial to estimate the effect of mobile screening and
treatment feedback on HbA1c and diabetes-related complications in Tshwane primary
health care clinics, South Africa.
AB - AIM AND OBJECTIVES: Our study had two primary objectives. The first was to
evaluate the effect of an expert review with an individualised patient management
plan on change in HbA1c. The second was to determine whether a mobile screening
unit would increase the proportion of patients screened for glycaemic and lipid
control, as well as diabetic complications as compared to the standard guideline
driven clinic care. METHODS: We conducted a cluster-randomised trial and enrolled
599 diabetic patients from twelve primary health care clinics in the Tshwane
district of South Africa. The study was carried out in three phases: Phase 1 was
a historical twelve-month record review to determine baseline characteristics;
Phase 2 was the provision of the intervention (active screening for metabolic
control and diabetes-related complications and health education targeting health
care workers and diabetic patients) compared to the control group (routine care
with similar education given to health care workers and diabetic patients) with a
follow-up which included a clinical assessment. Phase 3 was a repeat of the
record review to assess post-intervention changes following the proposed
individualised patient management plan in the intervention clinics, and self
initiated by the health care professionals in the control clinics, based on
training and results-sharing. RESULTS: No significant changes in the HbA1c
between the intervention and control clinics after one year were observed. The
mean Hba1c changed from 8.68 to 8.53% (intervention) and from 8.95 to 8.76%
(control) (p=0.92). Significant differences were observed in screening for
diabetic complications when active screening was done by a dedicated team. The
increase observed was more than 60% in all indicators monitored. Significant
changes were also seen in the control clinics for two measured outcome variables
(HbA1c test ordered from 15% to 25% (p=0.02) and serum-creatinine test ordered
increased from 11% to 19% (p<0.001)). There was no significant difference in the
proportion of actions taken, or not taken, between the control and interventions
arms (p=0.83). The proposed changed patient management plans by the expert review
team were implemented in only 29% of patients in the intervention arm.
CONCLUSIONS: A comprehensive programme that integrates clinical evaluations,
active screening and an individualised patient management plan did not lead to
significant improvement in the HbA1c levels. However, screening for glycaemic and
lipid control, as well as diabetic complications, improved dramatically with a
dedicated team. The lower than expected rate of uptake of the specialists
proposed patient management, with the resulting non-significant change in
glycaemic control, needs further investigation.
PMID- 28690090
TI - [Pituitary hyperplasia due to primary hypothyroidism].
AB - INTRODUCTION: Pituitary hyperplasia due to primary hypothyroidism is rare and
underdiagnosed. CASE REPORT: We report an 18-year-old patient referred for a
pituitary mass revealing primary hypothyroidism. Biological parameters confirmed
severe primary hypothyroidism and hyperprolactinemia. Outcome was favorable with
l-thyroxin supplementation resulting in TSH and prolactin levels normalization
and pituitary mass resolution. CONCLUSION: Pituitary hyperplasia due to primary
hypothyroidism, although rare, should be recognized to avoid unnecessary surgery
leading to irreversible complications.
PMID- 28690091
TI - [Paget's disease of bone: Diagnostic and therapeutic updates].
AB - Paget's disease of bone is the second most common metabolic bone disease after
osteoporosis. Its pathogenesis is not yet clearly understood. Geographic
distribution and epidemiological variations suggest a role of genetic and
environmental factors in its pathophysiology. The frequency of the Paget's
disease of bone increases with age. Its discovery can be fortuitous. Prognosis
mainly depends on the occurrence of complications involving bones and joints,
neurological, cardiovascular or metabolic systems. Treatment of symptomatic forms
currently relies on bisphosphonates that have transformed its prognosis.
PMID- 28690093
TI - [23rd session of the "spring of internal medicine": How to train to solve unique
cases?]
PMID- 28690092
TI - [Long-lasting thrombocytopenia induced by glycoprotein IIb/IIIa inhibitor].
AB - INTRODUCTION: Glycoprotein IIb/IIIa inhibitors (anti-GPIIbIIIa) prevent platelet
binding to fibrinogen. Transient sometimes-severe thrombocytopenia is a well
known side effect. OBSERVATION: A 71-year-old patient presented severe
thrombocytopenia after the administration of tirofiban (anti-GPIIbIIIa).
Corticosteroid treatment was initiated at day 10 because of persistence of severe
thrombocytopenia with poor platelet transfusion efficacy. Corticosteroid
treatment led to platelet recovery evoking an immune mediated mechanism for
thrombocytopenia. CONCLUSION: Anti-GPIIbIIIa are associated with a risk of
dramatic thrombocytopenia. The underlying mechanism is poorly understood. The
management of these usually transient thrombocytopenias is based on platelet
transfusion. As report here, in some cases persistent thrombocytopenia can
respond to corticosteroids.
PMID- 28690094
TI - [Relevance assessment of requests for antineutrophil cytoplasmic antibodies
detection: Retrospective study led in Bordeaux Hospital, France].
AB - INTRODUCTION: During year 2013, 5943 tests for antineutrophil cytoplasmic
antibodies (ANCA) detection were performed in Bordeaux hospital, France. This
seemed disproportionate, with regard to the low prevalence of ANCA-associated
vasculitis (AAV). Our purpose was to evaluate the relevance of these requests.
METHODS: Requests for detection of ANCA during 2013 were recorded, with their
results. A sample of 501 requests was secondarily established. Relevance of
requests was assessed independently by two reviewers. During year 2014, we
developed strategies of information, in order to reduce the number of requests
and increase their relevance. RESULTS: Only 17.8 % of the 5943 requests for
detection of ANCA resulted in a positive test using indirect immunofluorescence
(including 10.6 % of the requests with titles above 1/50). Using Luminex(c), 9.7
% of the test of detection against antimyeloperoxidase or antiproteinase 3
antibodies were positive. Within the sample of 501 patients, only 28.7 % of the
requests were relevant. A percentage of 40.2 of them weren't justified by a
clinical affection typically associated with AAV. Exactly 15.9 of the requests
were performed during systematic autoimmune screening. None of these requests
could lead to the diagnosis of AAV. Combination of information procedures and use
of a request form enabled a 19 % decrease of the number of requests. The
percentage of requests without clinical justification also reduced from 40.2 % to
17.1 %. The reduction of the number of requests led to a 46,865 ? saving.
CONCLUSION: The majority of the requests for detection of ANCA was not relevant
and could not lead to the diagnosis of AAV. Simple solutions enabled a partial
but significant improvement of their relevance.
PMID- 28690095
TI - Evolution of polyketide synthesis in a Dothideomycete forest pathogen.
AB - Fungal secondary metabolites have many important biological roles and some, like
the toxic polyketide aflatoxin, have been intensively studied at the genetic
level. Complete sets of polyketide synthase (PKS) genes can now be identified in
fungal pathogens by whole genome sequencing and studied in order to predict the
biosynthetic potential of those fungi. The pine needle pathogen Dothistroma
septosporum is predicted to have only three functional PKS genes, a small number
for a hemibiotrophic fungus. One of these genes is required for production of
dothistromin, a polyketide virulence factor related to aflatoxin, whose
biosynthetic genes are dispersed across one chromosome rather than being
clustered. Here we evaluated the evolution of the other two genes, and their
predicted gene clusters, using phylogenetic and population analyses. DsPks1 and
its gene cluster are quite conserved amongst related fungi, whilst DsPks2 appears
to be novel. The DsPks1 protein was predicted to be required for
dihydroxynaphthalene (DHN) melanin biosynthesis but functional analysis of DsPks1
mutants showed that D. septosporum produced mainly dihydroxyphenylalanine (DOPA)
melanin, which is produced by a PKS-independent pathway. Although the secondary
metabolites made by these two PKS genes are not known, comparisons between
strains of D. septosporum from different regions of the world revealed that both
PKS core genes are under negative selection and we suggest they may have
important cryptic roles in planta.
PMID- 28690096
TI - Modeling the effects of variable feeding patterns of larval ticks on the
transmission of Borrelia lusitaniae and Borrelia afzelii.
AB - Spirochetes belonging to the Borrelia burgdoferi sensu lato (sl) group cause Lyme
Borreliosis (LB), which is the most commonly reported vector-borne zoonosis in
Europe. B. burgdorferi sl is maintained in nature in a complex cycle involving
Ixodes ricinus ticks and several species of vertebrate hosts. The transmission
dynamics of B. burgdorferi sl is complicated by the varying competence of animals
for different genospecies of spirochetes that, in turn, vary in their capability
of causing disease. In this study, a set of difference equations simplifying the
complex interaction between vectors and their hosts (competent and not for
Borrelia) is built to gain insights into conditions underlying the dominance of
B. lusitaniae (transmitted by lizards to susceptible ticks) and the maintenance
of B. afzelii (transmitted by wild rodents) observed in a study area in Tuscany,
Italy. Findings, in agreement with field observations, highlight the existence of
a threshold for the fraction of larvae feeding on rodents below which the
persistence of B. afzelii is not possible. Furthermore, thresholds change as
nonlinear functions of the expected number of nymph bites on mice, and the
transmission and recovery probabilities. In conclusion, our model provided an
insight into mechanisms underlying the relative frequency of different Borrelia
genospecies, as observed in field studies.
PMID- 28690097
TI - A gamma-ray spectrometry analysis software environment.
AB - At the JRC-Geel's RadioNuclide Metrology sector, a Monte Carlo code based on
EGSnrc, and a general purpose calculation sheet implemented in Microsoft
Excel(r), have been developed to make the quantitative gamma-ray spectrometry
analysis of samples simpler and more robust. The further aim is that the software
can be used by non-experts in gamma-ray spectrometry e.g. external researchers
using JRC-Geel's facilities through the EUFRAT transnational access scheme. This
paper presents the developed Monte Carlo software and the functionality included
in the calculation sheet.
PMID- 28690098
TI - Mullerian Adenosarcoma of the Urinary Bladder: Clinicopathologic and
Immunohistochemical Features With Novel Genetic Aberrations.
AB - BACKGROUND: Mullerian adenosarcoma is a biphasic neoplasm most commonly occurring
in the uterus and less frequently of the ovary. It has been rarely described to
occur in other sites such as peritoneum and liver. PATIENTS AND METHODS: In this
study, we report the clinicopathologic, immunohistochemical and molecular
features of a primary Mullerian adenosarcoma of the urinary bladder in a 62-year
old woman. To our knowledge, this is the first report of detailed pathologic
characterization of Mullerian adenosarcoma primary to the urinary bladder in the
literature. RESULTS: Light microscopy showed a biphasic epithelial and stromal
tumor with benign-appearing glands surrounded by densely cellular endometrial
type stroma that is densely cellular with increased mitotic figures. The stroma
surrounding the glands was more cellular than the intervening areas, which were
more loose and edematous. Immunohistochemistry staining revealed positive
staining for Pax-2/8 within the glands, for positive CD10 and WT-1 within the
spindle cell stroma, and for estrogen and progesterone receptors in both.
Staining for desmin, GATA3, p63, and human papillomavirus was negative. Molecular
analyses identified mutations in protein kinase B E17K, fms related tyrosine
kinase 3 D835N, KRAS proto-oncogene, GTPase G12D, and HRAS proto-oncogene, GTPase
G12S. These novel molecular aberrations have yet to be reported in the medical
literature. X chromosome inactivation analysis revealed a clonal pattern in the
stromal component and a nonclonal pattern in the epithelial component. Currently,
the patient is disease/recurrence-free after regular follow-up of approximately
84 months. CONCLUSION: This case represents, to our knowledge, the first reported
diagnosis of Mullerian adenosarcoma arising in the urinary bladder with extensive
clinicopathologic, immunohistochemical, and molecular analyses.
PMID- 28690099
TI - Electrospun polymeric nanofibers: New horizons in drug delivery.
AB - Nanofibers obtained using electrospinning technique are being used since ages
especially in fields of textile industry, sensors, filters, protective clothing
and tissue engineering. Their use as drug delivery system is an emerging platform
in the field of pharmaceuticals and now-a-days formulation scientists are paying
great attention to the technology due to several advantages prime being easy
modulation of drug release profile depending upon the properties of
polymer/polymeric blends/other materials used. Although there are several reports
citing the use of antibiotics-loaded nanofibers as wound dressing materials and
as antimicrobial therapy in periodontics; still there is a good scope of
expanding the horizon for its application in newer ailments. This article reviews
various aspects related to loading and release of drug as such or in nano
particulate form to polymeric nanofibers by taking critical process parameters
(CPPs) for electrospinning and critical material attributes (CMAs) into account.
Commercially available products and electrospinning technologies are described in
brief along with some of the patents related to their use as drug delivery
systems. The main focus of this review is applicability of drug/drug nanoparticle
loaded nanofibers in the management of diseases/disorders related to the brain,
eye, ear, cardiovascular system, lungs and oral cavity. Use in diseases with
higher mortality rates like diabetes, Acquired immunodeficiency syndrome (AIDS)
and cancer is also described in brief.
PMID- 28690100
TI - Arginase purified from endophytic Pseudomonas aeruginosa IH2: Induce apoptosis
through both cell cycle arrest and MMP loss in human leukemic HL-60 cells.
AB - Arginase is a therapeutic enzyme for arginine-auxotrophic cancers but their low
anticancer activity, less proteolytic tolerance and shorter serum half-life are
the major shortcomings. In this study, arginase from Pseudomonas aeruginosa IH2
was purified to homogeneity and estimated as 75 kDa on native-PAGE and 37 kDa on
SDS-PAGE. Arginase showed optimum activity at pH 8 and temperature 35 degrees C.
Mn2+ and Mg2+ ions enhanced arginase activity while, Li+, Cu2+, and Al3+ ions
reduced arginase activity. In-vitro serum half-life of arginase was 36 h and
proteolytic half-life against trypsin and proteinase-K was 25 and 29 min,
respectively. Anticancer activity of arginase was evaluated against colon,
breast, leukemia, and prostate cancer cell lines and lowest IC50 (0.8 IU ml-1)
was found against leukemia cell line HL-60. Microscopic studies and flow
cytometric analysis of Annexin V/PI staining of HL-60 cells revealed that
arginase induced apoptosis in dose-dependent manner. Cell cycle analysis
suggested that arginase induced cell cycle arrest in G0/G1 phase. The increasing
level of MMP loss, ROS generation and decreasing level of SOD, CAT, GPx and GSH
suggested that arginase treatment triggered dysfunctioning of mitochondria. The
cleavage of caspase-3, PARP-1, activations of caspase-8, 9 and high expression of
proapoptotic protein Bax, low expression of anti-apoptotic protein Bcl-2
indicated that arginase treatment activates mitochondrial pathway of apoptosis.
Purified arginase did not exert cytotoxic effects on human noncancer cells. Our
study strongly supports that arginase could be used as potent anticancer agent
but further studies are required which are underway in our lab.
PMID- 28690102
TI - High frequency oscillations after median nerve stimulations in healthy children
and adolescents.
AB - The aim of the present research was to address somatosensory high frequency
oscillations (400-800Hz) in healthy children and adolescents in comparison with
healthy adults. We recorded somatosensory evoked potentials following median
nerve stimulation in nineteen resting healthy children/adolescents and in
nineteen resting healthy adults with eyes closed. We administered six consecutive
stimulation blocks (500 sweeps each). The presynaptic component of high frequency
oscillations amplitudes was smaller in healthy children/adolescents than in
healthy adults (no difference between groups was found as far as the postsynaptic
component was concerned). Healthy children/adolescents had smaller presynaptic
component than the postsynaptic one (the postsynaptic component amplitude was
145% of the presynaptic one), while healthy adults showed the opposite (reduction
of the postsynaptic component to 80% of the presynaptic one). No habituation
phenomena concerning high frequency oscillation amplitudes were registered in
neither healthy children/adolescents nor healthy adults. These findings suggest
that healthy children/adolescents present with significantly different pattern of
somatosensory high frequency oscillations compared with healthy adults' ones.
This different pattern is reasonably expression of higher cortical excitability
of the developing brain cortex.
PMID- 28690101
TI - Precise modulation of neuronal activity with synthetic photoswitchable ligands.
PMID- 28690103
TI - Risk communication and decision-making in the prevention of invasive breast
cancer.
AB - Risk communication surrounding the prevention of invasive breast cancer entails
not only understanding of the disease, risks and opportunities for intervention.
But it also requires understanding and implementation of optimal strategies for
communication with patients who are making these decisions. In this article,
available evidence for the issues surrounding risk communication and decision
making in the prevention of invasive breast cancer are reviewed and strategies
for improvement are discussed.
PMID- 28690104
TI - A clinical perspective on regional nodal irradiation for breast cancer.
AB - The goal of regional treatments in breast cancer should be to eradicate any
disease within lymph nodes, avoid regional recurrences, minimize the risk of
distant metastases, and improve survival. In addition, regional treatments should
focus on reducing potential morbidities and optimizing the long-term quality of
life of breast cancer survivors. While data from recent surgical and radiation
trials have helped clarify many issues regarding regional treatment, there still
remains controversy as to the optimal approach for patients with "intermediate
risk" disease. Two large radiation oncology studies (MA.20 and EORTC2292-10925)
evaluated whether more extensive lymphatic treatment benefited patients with
higher-risk lymph node-negative, or lower risk lymph node-positive disease. A
meta-analysis of these two studies suggested that the addition of regional nodal
irradiation (RNI) to the level III axillary, supraclavicular and upper internal
mammary lymph nodes conferred an improvement in disease free survival and distant
metastasis free survival as well as a 1-2% overall survival advantage. However,
other studies have suggested that many patients with positive sentinel lymph
nodes who are treated with breast conservation including breast irradiation may
safely avoid the morbidity and costs of further axillary treatment (whether
surgical or radiotherapy-based). In general, patients with 1-3 positive lymph
nodes or high-risk, node negative stage II breast cancer represent a diverse
population who require individualized, rather than group-based, risk assessment
when considering RNI. This article will propose a strategic methodology to assess
the modern day breast cancer patient's need for RNI in the setting of changing
surgical, radiation, and systemic therapies.
PMID- 28690105
TI - De-escalating and escalating systemic therapy in triple negative breast cancer.
AB - Triple negative breast cancer has the highest relapse risk of all the clinical
subsets, although the escalation of chemotherapy has benefited this subset
substantially over recent years. Systemic options are limited to chemotherapy,
which makes meaningful de-escalation or escalation of therapy more challenging
but possible. Observational cohorts suggest a less than 10% risk of relapse and
minimal if any benefit of chemotherapy in very small (<1 cm), node-negative
triple negative disease. In higher risk, particularly node-positive disease,
anthracycline/taxane-based regimens remain standard. Neoadjuvant chemotherapy
clearly de-escalates surgery, although there are insufficient data to give less
than standard chemotherapy on the basis of response to neoadjuvant therapy.
Efforts to meaningfully escalate therapy in high-risk disease have included
incorporating platinums into Neoadjuvant therapy, with clear benefit in pCR but
uncertain impact on relapse and survival at this time. Residual disease after
neoadjuvant chemotherapy carries a particularly poor prognosis; a recent
randomized trial of 6 months' capecitabine in this setting suggested a survival
advantage to this approach in higher risk residual disease. While not validated
at this time, future directions are likely to include biologic prognostication
with tumor and immune variables, as well as targeted non-cytotoxic approaches
leveraging the molecular heterogeneity of triple negative disease.
PMID- 28690106
TI - Current standards in oncoplastic breast conserving surgery.
AB - Oncoplastic breast conserving surgery is increasingly used to treat patients with
breast cancer. In the absence of randomized data, a large body of observational
evidence consistently indicates low rates of recurrence and high rates of
survival, but points to a higher rate of complications compared to conventional
breast conserving surgery. Established goals of oncoplastic breast conserving
surgery are to broaden the indication for breast conservation towards larger
tumors, and to improve esthetic outcomes. The benefit from the patient's
perspective, however, remains largely to be confirmed. There is a growing demand
to standardize various aspects of oncoplastic breast conserving surgery for
implementation in clinical research and practice. Several classification systems
and outcomes measurement tools have been proposed, but to the present day, none
of them has achieved international acceptance.
PMID- 28690107
TI - Preventing invasive breast cancer using endocrine therapy.
AB - Developments in breast cancer treatment have resulted in reduction in breast
cancer mortality in the developed world. However incidence continues to rise and
greater use of preventive interventions including the use of therapeutic agents
is needed to control this burden. High quality evidence from 9 major trials
involving more than 83000 participants shows that selective oestrogen receptor
modulators (SERMs) reduce breast cancer incidence by 38%. Combined results from 2
large trials with 8424 participants show that aromatase inhibitors (AIs) reduce
breast cancer incidence by 53%. These benefits are restricted to prevention of ER
positive breast cancers. Restricting preventive therapy to high-risk women
improves the benefit-harm balance and many guidelines now encourage healthcare
professionals to discuss preventive therapy in these women. Further research is
needed to improve our risk-prediction models for the identification of high risk
women for preventive therapy with greater accuracy and to develop surrogate
biomarkers of response. Long-term follow-up of the IBIS-I trial has provided
valuable insights into the durability of benefits from preventive therapy, and
underscores the need for such follow up to fully evaluate other agents. Full
utilisation of preventive therapy also requires greater knowledge and awareness
among both doctors and patients about benefits, harms and risk factors.
Healthcare professionals should routinely discuss preventive therapy with women
at high-risk of breast cancer.
PMID- 28690108
TI - Improving homing in T cell therapy.
AB - Cytotoxic T lymphocytes (cytotoxic T cells, CTLs) are an immune effector cell
population that can mediate specific immune responses against cancer. Based on
this concept, tumor immunotherapy protocols have been developed using adoptive
transfer of in vitro-expanded autologous T cells that can kill cancer cells.
However, fully functional adoptive T cell therapies (ACT) are hampered by the
inability to guarantee that all transferred T cells manage to reach the tumor
sites and make contact with cancer cells. The lack of tumor homing of T cells may
be caused by a variety of reasons. Stromal architecture and biological features
of the tumor microenvironment may act as barriers to T cell migration. A mismatch
between the chemokines released by the tumor or tumor stroma and the chemokine
receptors expressed on the transferred T cells may also impede T cell homing. The
identification of mechanisms responsible for cancer stroma remodeling is helping
to overcome the barriers of access to tumors, via novel therapeutic strategies
targeting tumor-stroma interactions. Simultaneously, recent studies have
demonstrated ways through which virally-transduced CTLs can be made to express
suitable chemokine receptors so as to enhance ACT, by improving CTL homing into
the tumor. Here we review the most important findings related to T cell
trafficking to the tumor, highlighting contributions that have led to promising
improvements in the available T cell therapy strategies. We discuss new possible
combinatorial strategies aimed to overcome chemokine mismatch, physical and
biological barriers and immunosuppression, so as to achieve more effective ACT
therapies.
PMID- 28690109
TI - Species Interactions Drive Fish Biodiversity Loss in a High-CO2 World.
AB - Accelerating climate change is eroding the functioning and stability of
ecosystems by weakening the interactions among species that stabilize biological
communities against change [1]. A key challenge to forecasting the future of
ecosystems centers on how to extrapolate results from short-term, single-species
studies to community-level responses that are mediated by key mechanisms such as
competition, resource availability (bottom-up control), and predation (top-down
control) [2]. We used CO2 vents as potential analogs of ocean acidification
combined with in situ experiments to test current predictions of fish
biodiversity loss and community change due to elevated CO2 [3] and to elucidate
the potential mechanisms that drive such change. We show that high risk-taking
behavior and competitive strength, combined with resource enrichment and collapse
of predator populations, fostered already common species, enabling them to double
their populations under acidified conditions. However, the release of these
competitive dominants from predator control led to suppression of less common and
subordinate competitors that did not benefit from resource enrichment and reduced
predation. As a result, local biodiversity was lost and novel fish community
compositions were created under elevated CO2. Our study identifies the species
interactions most affected by ocean acidification, revealing potential sources of
natural selection. We also reveal how diminished predator abundances can have
cascading effects on local species diversity, mediated by complex species
interactions. Reduced overfishing of predators could therefore act as a key
action to stall diversity loss and ecosystem change in a high-CO2 world. VIDEO
ABSTRACT.
PMID- 28690110
TI - Mapping Load-Bearing in the Mammalian Spindle Reveals Local Kinetochore Fiber
Anchorage that Provides Mechanical Isolation and Redundancy.
AB - Active forces generated at kinetochores move chromosomes, and the dynamic spindle
must robustly anchor kinetochore fibers (k-fibers) to bear this load. The
mammalian spindle bears the load of chromosome movement far from poles, but we do
not know where and how-physically and molecularly-this load distributes across
the spindle. In part, this is because probing spindle mechanics in live cells is
difficult. Yet answering this question is key to understanding how the spindle
generates and responds to force and performs its diverse mechanical functions.
Here, we map load-bearing across the mammalian spindle in space-time and dissect
local anchorage mechanics and mechanism. To do so, we laser-ablate single k
fibers at different spindle locations and in different molecular backgrounds and
quantify the immediate relaxation of chromosomes, k-fibers, and microtubule
speckles. We find that load redistribution is locally confined in all directions:
along the first 3-4 MUm from kinetochores, scaling with k-fiber length, and
laterally within ~2 MUm of k-fiber sides, without detectable load sharing between
neighboring k-fibers. A phenomenological model suggests that dense, transient
crosslinks to the spindle along k-fibers bear the load of chromosome movement but
that these connections do not limit the timescale of spindle reorganization. The
microtubule crosslinker NuMA is needed for the local load-bearing observed,
whereas Eg5 and PRC1 are not detectably required, suggesting specialization in
mechanical function. Together, the data and model suggest that NuMA-mediated
crosslinks locally bear load, providing mechanical isolation and redundancy while
allowing spindle fluidity. These features are well suited to support robust
chromosome segregation.
PMID- 28690112
TI - The Discovery of XY Sex Chromosomes in a Boa and Python.
AB - For over 50 years, biologists have accepted that all extant snakes share the same
ZW sex chromosomes derived from a common ancestor [1-3], with different species
exhibiting sex chromosomes at varying stages of differentiation. Accordingly,
snakes have been a well-studied model for sex chromosome evolution in animals [1,
4]. A review of the literature, however, reveals no compelling support that boas
and pythons possess ZW sex chromosomes [2, 5]. Furthermore, phylogenetic patterns
of facultative parthenogenesis in snakes and a sex-linked color mutation in the
ball python (Python regius) are best explained by boas and pythons possessing an
XY sex chromosome system [6, 7]. Here we demonstrate that a boa (Boa imperator)
and python (Python bivittatus) indeed possess XY sex chromosomes, based on the
discovery of male-specific genetic markers in both species. We use these markers,
along with transcriptomic and genomic data, to identify distinct sex chromosomes
in boas and pythons, demonstrating that XY systems evolved independently in each
lineage. This discovery highlights the dynamic evolution of vertebrate sex
chromosomes and further enhances the value of snakes as a model for studying sex
chromosome evolution.
PMID- 28690111
TI - Lateral Hypothalamic GABAergic Neurons Encode Reward Predictions that Are Relayed
to the Ventral Tegmental Area to Regulate Learning.
AB - Eating is a learned process. Our desires for specific foods arise through
experience. Both electrical stimulation and optogenetic studies have shown that
increased activity in the lateral hypothalamus (LH) promotes feeding. Current
dogma is that these effects reflect a role for LH neurons in the control of the
core motivation to feed, and their activity comes under control of forebrain
regions to elicit learned food-motivated behaviors. However, these effects could
also reflect the storage of associative information about the cues leading to
food in LH itself. Here, we present data from several studies that are consistent
with a role for LH in learning. In the first experiment, we use a novel GAD-Cre
rat to show that optogenetic inhibition of LH gamma-aminobutyric acid (GABA)
neurons restricted to cue presentation disrupts the rats' ability to learn that a
cue predicts food without affecting subsequent food consumption. In the second
experiment, we show that this manipulation also disrupts the ability of a cue to
promote food seeking after learning. Finally, we show that inhibition of the
terminals of the LH GABA neurons in ventral-tegmental area (VTA) facilitates
learning about reward-paired cues. These results suggest that the LH GABA neurons
are critical for storing and later disseminating information about reward
predictive cues.
PMID- 28690113
TI - Male Violence and Sexual Intimidation in a Wild Primate Society.
AB - Sexual violence occurring in the context of long-term heterosexual relationships,
such as sexual intimidation, is widespread across human populations [1-3].
However, its evolutionary origins remain speculative because few studies have
investigated the existence of comparable forms of sexual coercion in animals [4,
5], in which repeated male aggression toward a female provides the aggressor with
delayed mating benefits [6]. Here, we test whether male aggression toward females
functions as sexual coercion in wild chacma baboons (Papio ursinus). We found
support for all three main predictions of the sexual coercion hypothesis [7]:
male aggression (1) is greatest against cycling females, (2) is costly and
represents the main source of injuries for cycling females, and (3) increases
male mating success with their victims in the future. Detailed analysis of
chronological sequences between aggression and matings ruled out other coercive
mechanisms, such as short-term harassment and punishment, by showing that
aggression and matings are temporally decoupled. This decoupling may explain why
some forms of sexual violence have been largely overlooked in well-studied animal
populations despite their likely impact on the fitness of both sexes. Finally, we
found no support for alternative hypotheses such as a female preference for
aggressive males [8, 9]. This new, detailed study of the forms and intensity of
sexual intimidation in a wild primate suggests that it may be widespread across
mammalian societies, with important implications for understanding the evolution
of mate choice and sexual conflict in mammals, as well as the origins of human
sexual violence.
PMID- 28690115
TI - A Statistical Description of Plant Shoot Architecture.
AB - Plant architectures can be characterized statistically by their spatial density
function, which specifies the probability of finding a branch at each location in
the territory occupied by a plant. Using high-precision 3D scanning, we analyzed
557 plant shoot architectures, representing three species, grown across three to
five environmental conditions, and through 20-30 developmental time points. We
found two elegant properties in the spatial density functions of these
architectures: all functions could be nearly modified in one direction without
affecting the density in orthogonal directions (called "separability"), and all
functions shared the same underlying shape, aside from stretching and compression
(called "self-similarity"). Surprisingly, despite their striking visual
diversity, we discovered that all architectures could be described as variations
on a single underlying function: a Gaussian density function truncated at roughly
two SDs. We also observed systematic variation in the spatial density functions
across species, growth conditions, and time, which suggests functional
specialization despite following the same general design form.
PMID- 28690116
TI - Evaluating pathologic response of breast cancer to neoadjuvant chemotherapy with
computer-extracted features from contrast-enhanced ultrasound videos.
AB - PURPOSE: To extract quantitative perfusion and texture features with computer
assistance from contrast-enhanced ultrasound (CEUS) videos of breast cancer
before and after neoadjuvant chemotherapy (NAC), and to evaluate pathologic
response to NAC with these features. METHODS: Forty-two CEUS videos with 140,484
images were acquired from 21 breast cancer patients pre- and post-NAC. Time
intensity curve (TIC) features were calculated including the difference between
area under TIC within a tumor and that within a computer-detected reference
region (AUT_T-R). Four texture features were extracted including Homogeneity and
Contrast. All patients were identified as pathologic responders by Miller and
Payne criteria. The features between pre- and post-treatment in these responders
were statistically compared, and the discrimination between pre- and post
treatment cancers was assessed with a receiver operating characteristic (ROC)
curve. RESULTS: Compared with the pre-treatment cancers, the post-treatment
cancers had significantly lower Homogeneity (p<0.001) and AUT_T-R (p=0.014), as
well as higher Contrast (p<0.001), indicating the intratumoral contrast
enhancement decreased and became more heterogeneous after NAC in responders. The
combination of Homogeneity and AUT_T-R achieved an accuracy of 90.5% and area
under ROC curve of 0.946 for discrimination between pre- and post-chemotherapy
cancers without cross validation. The accuracy still reached as high as 85.7%
under leave-one-out cross validation. CONCLUSIONS: The computer-extracted CEUS
features show reduced and more heterogeneous neovascularization of cancer after
NAC. The features achieve high accuracy for discriminating between pre- and post
chemotherapy cancers in responders and thus are potentially valuable for tumor
response evaluation in clinical practice.
PMID- 28690114
TI - Maintenance of Miranda Localization in Drosophila Neuroblasts Involves
Interaction with the Cognate mRNA.
AB - How cells position their proteins is a key problem in cell biology. Targeting
mRNAs to distinct regions of the cytoplasm contributes to protein localization by
providing local control over translation. Here, we reveal that an interdependence
of a protein and cognate mRNA maintains asymmetric protein distribution in
mitotic Drosophila neural stem cells. We tagged endogenous mRNA or protein
products of the gene miranda that is required for fate determination with GFP. We
find that the mRNA localizes like the protein it encodes in a basal crescent in
mitosis. We then used GFP-specific nanobodies fused to localization domains to
alter the subcellular distribution of the GFP-tagged mRNA or protein. Altering
the localization of the mRNA resulted in mislocalization of the protein and vice
versa. Protein localization defects caused by mislocalization of the cognate mRNA
were rescued by introducing untagged mRNA coding for mutant non-localizable
protein. Therefore, by combining the MS2 system and subcellular nanobody
expression, we uncovered that maintenance of Mira asymmetric localization
requires interaction with the cognate mRNA.
PMID- 28690117
TI - Preparedness and the importance of meeting the needs of healthcare workers: a
qualitative study on Ebola.
AB - BACKGROUND: Healthcare workers (HCWs) face specific challenges in infectious
disease outbreaks, which provide unusual, new events with exposure risk. The fear
of infection or new, unknown tasks in an unfamiliar setting, for example, may
complicate outbreak management. AIM: To gain insight into how healthcare
organizations can prepare to meet the needs of their HCWs by capturing the
experiences of HCWs with patients with suspected Ebola virus disease. METHODS: We
conducted 23 in-depth interviews with HCWs, of whom 20 worked in a Dutch
university hospital and three worked in a regional ambulance service. We invited
HCWs who cared for patients with suspected Ebola or who were on the team
preparing for admission of such patients in the period 2014-2015. FINDINGS: The
HCWs were stressed and anxious, but most rated their overall experience as
positive. We categorized the reported experiences in three main themes, namely,
experiences related to: (i) the novelty of the threat, (ii) the risk of infection
and fear of transmission, and (iii) the excessive attention. Our results
underline the importance of a supportive working environment suitable for crises.
CONCLUSION: The experiences of HCWs dealing with patients with suspected Ebola
can direct improvements in generic preparedness for highly transmissible
diseases.
PMID- 28690118
TI - Clinical outcomes of percutaneous coronary intervention with rotablation in
patients with acute or recent myocardial infarction.
AB - BACKGROUND: Although rotational atherectomy (RA) has been an accepted and widely
used medical procedure for more than 15 years, the clinical outcomes of RA in
high-risk populations remain elusive. Therefore, the purpose of this study was to
investigate the safety and efficacy of RA for patients with acute or recent
myocardial infarction (MI), and report the short- and long-term clinical outcomes
in this population. METHODS: We enrolled patients undergoing percutaneous
coronary intervention (PCI) and RA at two medical centers in Taiwan between
January 2004 and December 2013. Individuals who suffered an acute MI within 30
days before RA were assigned to the MI group; the remaining subjects were
assigned to the non-MI group. RESULTS: A total of 154 subjects were enrolled in
our study, among them: 47 (30.5%) had an acute MI within 30 days of RA (MI
group), and the remaining 107 (69.5%) patients without MI comprised the non-MI
group. PCI and RA procedures were performed successfully in 150 patients. The 30
day and 1-year total death, MI, and major adverse cardiac event (MACE included
all-cause death, MI, and clinical-driven target lesion revascularization) rates
were 6.5%, 12.3%, and 15.6%, and 9.7%, 15.2%, and 30.5%, at the 30-day and 1-year
follow-ups, respectively. MI was identified as an independent predictor for both
30-day MACE and total death (MACE, OR: 3.95, P = 0.006; total death, OR: 4.67, P
= 0.043), and remained an independent predictor for 1-year total death and MI
(total death, HR: 4.47, P = 0.007; MI, HR: 2.62, P = 0.016). CONCLUSION: Our
study demonstrated the safety and efficacy of RA in patients with acute or recent
MI, and identified MI as an independent predictor of both short- and long-term
outcomes.
PMID- 28690119
TI - Cholesterol-lowering effect of Aralia elata (Miq.) Seem via the activation of
SREBP-2 and the LDL receptor.
AB - BACKGROUND: Hyperlipidemia causes arteriosclerosis, a risk factor for coronary
heart disease. Prevention of hyperlipidemia by improving dietary habits has
recently attracted attention. In this regard, we investigated whether Aralia
elata (Miq.) Seem (AE) extract inhibits hepatic cholesterol accumulation and
modulate the cellular signaling pathway. METHODS: To determine AE's cholesterol
regulating mechanism, we measured cholesterol level, 3-hydroxy-3-methylglutaryl
coenzyme A (HMG-CoA) reductase activity and cholesterol regulating-related gene
expression in HepG2 cells and in high-fat diet (HFD)-induced mice using ELISA and
RT-PCR assay. RESULTS: The AE extract reduced cholesterol levels and HMG-CoA
reductase activity in hepatocellular carcinoma HepG2 cells. In addition, it also
reduced the plasma cholesterol concentrations in HFD-induced mice. Furthermore,
the AE extract increased the gene expression of the LDL-receptor (LDL-R); sterol
regulatory-element binding protein-2 (SREBP-2); ATP-binding cassette, sub-family
A, member 1 (ABCA1); and scavenger receptor class B member 1 (SR-B1) in a dose
dependent manner. However, the AE extract did not affect the gene expression of
acetyl-coenzyme A acetyltransferase (ACAT) in either the HepG2 cells or mice.
CONCLUSION: We demonstrated that the AE extract activated genes related to
cholesterol metabolism, such as SREBP-2 and LDL-R, which resulted in
hypocholesterolemic activities.
PMID- 28690120
TI - The prognosis outcome of oral squamous cell carcinoma using HIF-2alpha.
AB - BACKGROUND: Hypoxia-induced factors (HIF) has a role in angiogenesis and regulate
tumorigenesis of cancer cell. The HIF is the best-identified mechanism that shows
imbalance between consumption and oxygen supply in progressing tumor. This study
of HIF-2alpha expression in oral squamous cell carcinoma (OSCC) aimed to
investigate the relationship of HIF-2alpha and pathology characteristics related
to its clinical correlation. METHODS: Fifty-eight samples of OSCC and adjacent
tissues were fixed in paraffin for microarray preparation. The tissue array then
was stained using primary antibody HIF-2alpha (NB100-122) and autoprobe II ABC
universal staining kit. Each tissue sample was captured using camera microscope,
and images were analyzed with Photoshop 6.0 using the CMYK method. A statistical
analysis was performed with the two-tailed t-test, Kaplan-Meier and log-rank test
using Prism for Windows version 5.0. RESULTS: The samples of the non-cancerous
matched tissues (NCMTs) paired with their OSCC samples showed HIF-2alpha
overexpression with significance difference p < 0.0001. Although no significant
difference was found between HIF-2alpha expression and overall survival rate,
cancer-specific survival rate, and disease-free survival rate, the HIF-2alpha
expression showed statistical significance for overall cancer stages with p =
0.013. In addition, patients with high HIF-2alpha expression tended to develop
recurrence within 2 years compared to the low expression group. CONCLUSION: HIF-2
expression has complicated roles in different cancer types, including OSCC. Our
study indicated that HIF-2alpha overexpression can serve as a good biomarker for
cancer status for all tumor stages and may predict an early recurrence within two
years.
PMID- 28690121
TI - Assessment of factors that could affect the success of US-guided contrast
injection for hip MR arthrography.
AB - BACKGROUND: To retrospectively evaluate the association between possible
influencing factors and failed first attempts to inject a contrast agent intra
articularly under ultrasound (US)-guidance for direct magnetic resonance (MR)
arthrography of the hip joint. METHODS: Ninety consecutive patients (38 women and
52 men; mean age, 42 years) undergoing US-guided hip MR arthrography (3
bilaterally) were retrospectively included in this study. The potential
influencing factors were sex, age, body mass index (BMI), side of injection,
target site, trajectory of the needle, additional use of needle tip rotation,
failed first-attempt, and capsule elongation at the site of needle insertion.
RESULTS: First-attempt failure was significantly associated with reduced capsule
elongation at the target site and no additional use of needle tip rotation (OR
10.708; 95% CI 1.847-62.059; OR 3.518; 95% CI 1.120-11.047). Capsule elongation
(sufficient for needle bevel insertion) was significantly larger at the femoral
head-neck junction (5.2 +/- 1.5 mm) than at the femoral head (2.9 +/- 1.3 mm) (p
< 0.001). CONCLUSION: Less capsular elongation of the femoral head and no
additional use of needle tip rotation to reduce the difficulty in contrast
material delivery can increase the first-attempt failure rate in patients
undergoing US-guided hip arthrography.
PMID- 28690122
TI - Hepatoprotective effects of ethanol extracts from Folium Syringae against
acetaminophen-induced hepatotoxicity in vitro and in vivo.
AB - BACKGROUND: The leaves of Folium Syringae (FS) have been long used as a
traditional Chinese folk medicine for their anti-inflammatory effect, utilized as
an antibacterial and antiviral treatment. The purpose of this study was to
investigate the potential hepatoprotective effects of FS on acetaminophen-induced
hepatic injury in primary hepatocytes and mice. METHODS: Hepatocytes obtained by
the inverse perfusion method were divided randomly into five groups. Prior to
acetaminophen exposure, 3 different doses of FS ethanol extracts were given to
hepatocytes and mice, respectively. Thereafter, transaminases, glutathione S
transferase A1 (GSTA1) and some hepatic indices were determined. RESULTS: FS
ethanol extracts (200 MUg/mL) pretreatment prevented all of the alterations,
returning their levels to nearly those levels observed in the control group in
vitro. Treatment with FS ethanol extracts (200 mg/kg) significantly reduced the
toxicity induced by acetaminophen in vivo, which manifested as a decrease in
transaminases, and the hepatoprotective effects of FS were similar to Silymarin
(positive group). GSTA1 represented the same change trend as transaminases and
hepatic indices, and at a dose of 100 MUg/mL FS ethanol extracts in vitro and 100
mg/kg in vivo, GSTA1 content changed significantly (p < 0.01), but transaminases
were insignificant (p > 0.05). CONCLUSION: The results of our investigation
suggested that FS ethanol extracts possess significant protective effects against
hepatotoxicity induced by acetaminophen both in vitro and in vivo. In addition,
GSTA1 could be used as an indicator assessing the extents of hepatic injury,
which is more sensitive than transaminases.
PMID- 28690123
TI - Pedicled omental flaps in the treatment of complex spinal wounds after en bloc
resection of spine tumors.
AB - STUDY DESIGN: The present paper presents a retrospective study of 5 patients who
underwent pedicled omental flap procedure following spine tumor removal. SUMMARY
OF BACKGROUND DATA: Postoperative wound dehiscence represents a major
complication in spinal surgery, particularly after en bloc tumor resection,
because of the extended sacrifice of soft tissues and adjuvant radiation therapy
and chemotherapy. METHODS: Five patients, with a mean age of 52 years (range, 24
71 years), who underwent omental flaps for the treatment of postoperative
complication in spine tumor resections were retrospectively evaluated. RESULTS:
Four of 5 patients underwent omental transposition after a mean of 15 months
(range, 4-27) from the previous surgery because of dehiscence of the wound (all
of them had cerebrospinal fluid leak: 1 transpleural and in 3 cases, associated
with deep infection), whereas one patient underwent the omental flap procedure at
the time of elective spinal surgery because of several contemporary risk factors
for wound healing. At the time of discharge after a mean of 36 days (range, 23
53), all patients had well-healed surgical wounds with an acceptable structural
and aesthetic result. One of the patients had ileus, requiring surgical lysis of
abdominal adhesions 3 months after omentum flap procedure. No other complications
were observed. CONCLUSION: Our data suggest that pedicled omental flap is a
viable option for the treatment of complicated spinal wounds, helping in the
resolution of the infection and CSF leak.
PMID- 28690124
TI - Microneedling: Where do we stand now? A systematic review of the literature.
AB - BACKGROUND: Patients who suffer from scars or wrinkles have several therapeutic
options to improve the appearance of their skin. The available treatment
modalities that provide desirable results are often overtly invasive and entail a
risk of undesirable adverse effects. Microneedling has recently emerged as a non
ablative alternative for treating patients who are concerned with the aesthetic
changes that result from injury, disease or ageing. OBJECTIVE: This review aims
to evaluate the current evidence in the literature on microneedling. METHODS: A
systematic literature review was performed by searching the electronic databases
PubMed and Google Scholar. The reviewed articles were analysed and compared on
study design, treatment protocol, outcome parameters, efficacy measurement and
results to evaluate the strength of the current evidence. RESULTS: Microneedling
was investigated in experimental settings for its effects on atrophic acne scars,
skin rejuvenation, hypertrophic scars, keloids, striae distensae, androgenetic
alopecia, melasma and acne vulgaris. Several clinical trials used randomisation
and single-blindation to strengthen the validity of the study outcome.
Microneedling showed noteworthy results when used on its own and when combined
with topical products or radiofrequency. When compared with other treatments, it
showed similar results but was preferred due to minimal side effects and shorter
downtime. CONCLUSION: This systematic review positions microneedling as a safe
and effective therapeutic option for the treatment of scars and wrinkles. The
current literature does show some methodological shortcomings, and further
research is required to truly establish microneedling as an evidence-based
therapeutic option for treating scars, wrinkles and other skin conditions.
PMID- 28690125
TI - Carbamylation is a competitor of glycation for protein modification in vivo.
AB - AIM: Chronic kidney disease (CKD) and diabetes mellitus are two diseases that
accelerate protein molecular ageing through carbamylation and glycation
reactions, characterized by the binding of urea-derived isocyanic acid and of
sugars on proteins, respectively. These two reactions target the same protein
amino groups and, thus, compete with each other. Such competition may arise
especially in diabetic patients with nephropathy. This study aimed to evaluate
their potential competitive effects in vitro and under conditions reproducing CKD
and/or diabetes in vivo. METHODS: Albumin was incubated in vitro with glucose,
urea or cyanate. Carbamylation in vivo was enhanced in normal and diabetic
(db/db) mice by either subtotal nephrectomy or cyanate consumption.
Homocitrulline, carbamylated haemoglobin and furosine were measured by LC-MS/MS,
fructosamine by colorimetric assay and HbA1c by immunological assay. RESULTS:
Reciprocal inhibition between carbamylation and glycation was observed during
albumin incubations in vitro. Besides, 5 weeks after induction of CKD in vivo,
plasma homocitrulline concentrations were similar in both diabetic and non
diabetic mice, whereas fructosamine and HbA1c were decreased (-23% and -42%,
respectively) in diabetic mice with CKD compared with only diabetic ones.
Fructosamine and HbA1c were also decreased in cyanate-spiked water-drinking mice
compared with plain water-drinking diabetic mice. CONCLUSION: Carbamylation
competes with glycation in vivo, especially under conditions of high glycation.
Thus, the classic markers of glycaemic control should be interpreted with caution
in diabetic patients with CKD because of this competitive effect.
PMID- 28690126
TI - [MRI-based radiotherapy planning].
AB - MRI-based radiotherapy planning is a topical subject due to the introduction of a
new generation of treatment machines combining a linear accelerator and a MRI.
One of the issues for introducing MRI in this task is the lack of information to
provide tissue density information required for dose calculation. To cope with
this issue, two strategies may be distinguished from the literature. Either a
synthetic CT scan is generated from the MRI to plan the dose, or a dose is
generated from the MRI based on physical underpinnings. Within the first group,
three approaches appear: bulk density mapping assign a homogeneous density to
different volumes of interest manually defined on a patient MRI; machine learning
based approaches model local relationship between CT and MRI image intensities
from multiple data, then applying the model to a new MRI; atlas-based approaches
use a co-registered training data set (CT-MRI) which are registered to a new MRI
to create a pseudo CT from spatial correspondences in a final fusion step. Within
the second group, physics-based approaches aim at computing the dose directly
from the hydrogen contained within the tissues, quantified by MRI. Excepting the
physics approach, all these methods generate a synthetic CT called "pseudo CT",
on which radiotherapy planning will be finally realized. This literature review
shows that atlas- and machine learning-based approaches appear more accurate
dosimetrically. Bulk density approaches are not appropriate for bone
localization. The fastest methods are machine learning and the slowest are atlas
based approaches. The less automatized are bulk density assignation methods. The
physical approaches appear very promising methods. Finally, the validation of
these methods is crucial for a clinical practice, in particular in the
perspective of adaptive radiotherapy delivered by a linear accelerator combined
with an MRI scanner.
PMID- 28690127
TI - Striking pseudogenization in avian phylogenetics: Numts are large and common in
falcons.
AB - Nuclear copies of mitochondrial genes (numts) are a well-known feature of
eukaryotic genomes and a concern in systematics, as they can mislead phylogenetic
inferences when inadvertently used. Studies on avian numts initially based on the
chicken genome suggest that numts may be uncommon and relatively short among
birds. Here we ask how common numts are in falcons, based on recently sequenced
genomes of the Saker falcon (Falco cherrug) and Peregrine falcon (F. peregrinus).
We identified numts by BLASTN searches and then extracted CYTB, ND2 and COI
sequences from them, which were then used for phylogeny inference along with
several sequences from other species in Falconiformes. Our results indicate that
avian numts may be much more frequent and longer than previously thought.
Phylogenetic inferences revealed multiple independent nuclear insertions
throughout the history of the Falconiformes, including cases of sequences
available in public databases and wrongly identified as authentic mtDNA. New
sequencing technologies and ongoing efforts for whole genome sequencing will
provide exciting opportunities for avian numt research in the near future.
PMID- 28690128
TI - A qualitative case study of ehealth and digital literacy experiences of pharmacy
staff.
AB - BACKGROUND: eHealth's many forms are benchmarked by the World Health
Organization. Scotland is considered an advanced adopter of ehealth. The third
global survey on ehealth includes pharmacy-related ehealth indicators. Advances
in ehealth place an obligation on pharmacy staff to demonstrate proficiency, or
digital literacy, in using ehealth technologies. OBJECTIVE: The aim of this study
was to provide an indepth exploration of the ehealth and digital literacy
experiences of pharmacy staff in the North East of Scotland. METHOD: A
qualitative local case study approach was adopted for observational and interview
activities in community and hospital pharmacies. Interview and observational data
were collated and analysed using a framework approach. This study gained
management approval from the local health board following ethical review by the
sponsor university. RESULTS: Nineteen pharmacies and staff (n = 94) participated
including two hospitals. Most participants were female (n = 82), aged 29 years
and younger (n = 34) with less than 5 years pharmacy experience (n = 49).
Participants identified their own digital literacy as basic. Most of the
pharmacies had minimum levels of technology implemented (n = 15). Four themes
(technology, training, usability, processes) were inducted from the data, coded
and modelled with illustrative quotes. CONCLUSION: Scotland is aspirational in
seeking to support the developing role of pharmacy practice with ehealth,
however, evidence to date shows most pharmacy staff work with minimum levels of
technology. The self-reported lack of digital literacy and often mentioned lack
of confidence in using IT suggest pharmacy staff need support and training.
Informal work based digital literacy development of the pharmacy team is self
limiting. Usability of ehealth technology could be a key element of its'
acceptability. There is potential to better engage with ehealth process
efficiencies in both hospital and community pharmacy. As Scotland increasingly
invests in ehealth pharmacy technology, it is important that it also invests in
pharmacy staff training.
PMID- 28690129
TI - Graph theoretical analysis of functional network for comprehension of sign
language.
AB - Signed languages are natural human languages using the visual-motor modality.
Previous neuroimaging studies based on univariate activation analysis show that a
widely overlapped cortical network is recruited regardless whether the sign
language is comprehended (for signers) or not (for non-signers). Here we move
beyond previous studies by examining whether the functional connectivity profiles
and the underlying organizational structure of the overlapped neural network may
differ between signers and non-signers when watching sign language. Using graph
theoretical analysis (GTA) and fMRI, we compared the large-scale functional
network organization in hearing signers with non-signers during the observation
of sentences in Chinese Sign Language. We found that signed sentences elicited
highly similar cortical activations in the two groups of participants, with
slightly larger responses within the left frontal and left temporal gyrus in
signers than in non-signers. Crucially, further GTA revealed substantial group
differences in the topologies of this activation network. Globally, the network
engaged by signers showed higher local efficiency (t(24)=2.379, p=0.026), small
worldness (t(24)=2.604, p=0.016) and modularity (t(24)=3.513, p=0.002), and
exhibited different modular structures, compared to the network engaged by non
signers. Locally, the left ventral pars opercularis served as a network hub in
the signer group but not in the non-signer group. These findings suggest that,
despite overlap in cortical activation, the neural substrates underlying sign
language comprehension are distinguishable at the network level from those for
the processing of gestural action.
PMID- 28690130
TI - Investigating the variation in the incidence of new Pseudomonas aeruginosa
infection between paediatric cystic fibrosis centres.
PMID- 28690131
TI - Country, regional, and global estimates for lactose malabsorption in adults: a
systematic review and meta-analysis.
AB - BACKGROUND: Studies have shown wide variation in the prevalence of lactose
malabsorption across the world, but no systematic reviews or meta-analyses have
recently assessed the prevalence of lactose malabsorption in different
geographical areas. We aimed to present an updated systematic review and meta
analysis on the prevalence of lactose malabsorption in adults, by countries and
regions, and to assess the variation between different testing methods. METHODS:
Studies reporting on prevalence of lactose malabsorption and lactase persistence
were identified by searching MEDLINE and Embase from database inception to Nov 2,
2016. We evaluated studies presenting lactose malabsorption or lactase
persistence prevalence data in adults and children aged 10 years or older,
including cross-sectional and prospective studies, using genotyping, hydrogen
breath tests, lactose tolerance tests, and other testing methods. We excluded
studies in children younger than 10 years, studies using self-reported data, and
studies including inpatients and outpatients at gastroenterological wards.
Studies were screened by two authors (CLS and SKF) and data values were extracted
by two authors (CLS and SKF) independently. The primary outcome was the
prevalence of lactose malabsorption. This study is registered with PROSPERO,
number CRD42017064802. FINDINGS: We screened 2665 records, and 306 study
populations from 116 full-text articles were included (primary sources); data for
144 additional study populations from 59 articles were obtained from review
articles, because full-text primary articles could not be obtained (secondary
sources). Of the 450 study populations included, 231 were assessed by genotyping,
83 by hydrogen breath tests, 101 by lactose tolerance tests, and 35 by other
methods or methods that were not described sufficiently. The studies included 62
910 participants from 89 countries (covering 84% of the world's population). When
standardising for country size, the global prevalence estimate of lactose
malabsorption was 68% (95% CI 64-72), ranging from 28% (19-37) in western,
southern, and northern Europe to 70% (57-83) in the Middle East. When assessing
the global prevalence using genotyping data only, the estimate was 74% (69-80),
whereas prevalence was 55% (46-65) using lactose tolerance test data, and 57% (46
67) using hydrogen breath test data. Risk of bias was assessed based on ten
indicators; 12 of the articles had a score of ten, indicating low risk of bias,
76 had a score of nine, 26 a score of eight, and two articles a score of seven
(indicating higher risk of bias). There was substantial heterogeneity between
studies within most of the assessed countries. INTERPRETATION: Lactose
malabsorption is widespread in most of the world, with wide variation between
different regions and an overall frequency of around two-thirds of the world's
population. Acknowledging regional patterns of lactose malabsorption is important
to guide management of gastrointestinal symptoms. FUNDING: None.
PMID- 28690132
TI - What is normal and abnormal in lactose digestion?
PMID- 28690133
TI - The complete genome sequence of Bacillus velezensis strain GH1-13 reveals
agriculturally beneficial properties and a unique plasmid.
AB - The bacterial strain Bacillus velezensis GH1-13, isolated from rice paddy soil in
Korea, has been shown to promote plant growth and have strong antagonistic
activities against pathogens. Here, we report the complete genome sequence of GH1
13, revealing that it possesses a single 4,071,980-bp circular chromosome with
46.2% GC-content. The chromosome encodes 3,930 genes, and we have also identified
a unique plasmid in the strain that encodes a further 104 genes (71,628bp and
31.7% GC-content). The genome was found to contain various enzyme-encoding
operons, including indole-3-acetic acid (IAA) biosynthesis proteins, 2,3
butanediol dehydrogenase, various non-ribosomal peptide synthetases, and several
polyketide synthases. These properties are responsible for the promotion of plant
growth and the biosynthesis of secondary metabolites. They therefore have
multiple beneficial effects that could be applied to agriculture. Through curing,
we found that the unique plasmid of GH1-13 has important roles in the production
of phytohormones, such as IAA, and in shaping phenotypic and physiological
characteristics. The plasmid therefore likely influences the biological
activities of GH1-13. The complete genome sequence of B. velezensis GH1-13
contributes to our understanding of this beneficial strain and will encourage
research into its development for agricultural or biotechnological applications,
enhancing productivity and crop quality.
PMID- 28690134
TI - Recent advances in RNA folding.
AB - In the realm of nucleic acid structures, secondary structure forms a conceptually
important intermediate level of description and explains the dominating part of
the free energy of structure formation. Secondary structures are well conserved
over evolutionary time-scales and for many classes of RNAs evolve slower than the
underlying primary sequences. Given the close link between structure and
function, secondary structure is routinely used as a basis to explain
experimental findings. Recent technological advances, finally, have made it
possible to assay secondary structure directly using high throughput methods.
From a computational biology point of view, secondary structures have a special
role because they can be computed efficiently using exact dynamic programming
algorithms. In this contribution we provide a short overview of RNA folding
algorithms, recent additions and variations and address methods to align,
compare, and cluster RNA structures, followed by a tabular summary of the most
important software suites in the fields.
PMID- 28690135
TI - Genome editing in Shiraia bambusicola using CRISPR-Cas9 system.
AB - Shiraia bambusicola can produce a type of hypocrellin, which is applied in
antibacterial, antitumoral, and antiviral areas. Studies on the hypocrellin
pathway have not been confirmed due to the deficiency of suitable genetic
methods. We constructed a clustered regularly interspaced short palindromic
repeat sequences (CRISPR)/Cas9 system in Shiraia sp. SUPER-H168 and targeted a
polyketide synthase (SbaPKS). No hypocrellin production was detected in the
DeltaSbaPKS mutant. Relative expression levels of SbaPKS and its adjacent genes
were extremely down-regulated in the DeltaSbaPKS mutant compared to those in the
wild strain. Subsequent pathogenicity assays showed that deletion of SbaPKS
attenuated virulence on bamboo leaves. In contrast, restored hypocrellin in a
SbaPKS overexpression strain generated necrotic lesions on bamboo leaves. These
results suggest that SbaPKS is involved in hypocrellin biosynthesis and
hypocrellin has an essential role in the virulence of S. bambusicola on bamboo
leaves. The CRISPR/Cas9 system in Shiraia sp. will open an avenue for decoding
the hypocrellin pathway and genome editing of other filamentous fungi. Strategies
that disrupt hypocrellin biosynthesis may reduce the detriment of S. bambusicola.
PMID- 28690136
TI - Drug delivery devices for retinal diseases.
AB - Retinal degenerative diseases are a leading cause of irreversible blindness and
visual impairment, affecting millions of people worldwide. Although intravitreal
injection can directly deliver drugs to the posterior segment of the eye, it is
invasive and associated with serious side effects. The design of drug delivery
systems targeting the posterior segment of the eye in a less invasive manner has
still been challenging because of various anatomical and physiological barriers.
In this review, we provide an overview of the current implant device-based
approaches used for treating retinal degenerative diseases. We then offer our
perspectives on future directions and challenges that remain for developing more
effective device-based therapies for retinal diseases.
PMID- 28690137
TI - Cost-effectiveness of population based BRCA testing with varying Ashkenazi Jewish
ancestry.
AB - BACKGROUND: Population-based BRCA1/BRCA2 testing has been found to be cost
effective compared with family history-based testing in Ashkenazi-Jewish women
were >30 years old with 4 Ashkenazi-Jewish grandparents. However, individuals may
have 1, 2, or 3 Ashkenazi-Jewish grandparents, and cost-effectiveness data are
lacking at these lower BRCA prevalence estimates. We present an updated cost
effectiveness analysis of population BRCA1/BRCA2 testing for women with 1, 2, and
3 Ashkenazi-Jewish grandparents. STUDY DESIGN: Decision analysis model. METHODS:
Lifetime costs and effects of population and family history-based testing were
compared with the use of a decision analysis model. 56% BRCA carriers are missed
by family history criteria alone. Analyses were conducted for United Kingdom and
United States populations. Model parameters were obtained from the Genetic Cancer
Prediction through Population Screening trial and published literature. Model
parameters and BRCA population prevalence for individuals with 3, 2, or 1
Ashkenazi-Jewish grandparent were adjusted for the relative frequency of BRCA
mutations in the Ashkenazi-Jewish and general populations. Incremental cost
effectiveness ratios were calculated for all Ashkenazi-Jewish grandparent
scenarios. Costs, along with outcomes, were discounted at 3.5%. The time horizon
of the analysis is "life-time," and perspective is "payer." Probabilistic
sensitivity analysis evaluated model uncertainty. RESULTS: Population testing for
BRCA mutations is cost-saving in Ashkenazi-Jewish women with 2, 3, or 4
grandparents (22-33 days life-gained) in the United Kingdom and 1, 2, 3, or 4
grandparents (12-26 days life-gained) in the United States populations,
respectively. It is also extremely cost-effective in women in the United Kingdom
with just 1 Ashkenazi-Jewish grandparent with an incremental cost-effectiveness
ratio of L863 per quality-adjusted life-years and 15 days life gained. Results
show that population-testing remains cost-effective at the L20,000-30000 per
quality-adjusted life-years and $100,000 per quality-adjusted life-years
willingness-to-pay thresholds for all 4 Ashkenazi-Jewish grandparent scenarios,
with >=95% simulations found to be cost-effective on probabilistic sensitivity
analysis. Population-testing remains cost-effective in the absence of reduction
in breast cancer risk from oophorectomy and at lower risk-reducing mastectomy
(13%) or risk-reducing salpingo-oophorectomy (20%) rates. CONCLUSION: Population
testing for BRCA mutations with varying levels of Ashkenazi-Jewish ancestry is
cost-effective in the United Kingdom and the United States. These results support
population testing in Ashkenazi-Jewish women with 1-4 Ashkenazi-Jewish
grandparent ancestry.
PMID- 28690138
TI - Chinese herbal medicine for Alzheimer's disease: Clinical evidence and possible
mechanism of neurogenesis.
AB - Currently, there is lack of cure or disease-modifying treatment for Alzheimer's
disease (AD). Chinese herbal medicine (CHM) is purported to ameliorate AD
progression, perhaps by promoting hippocampal neurogenesis. Here, we conducted an
updated systematic review to investigate the efficacy and safety of CHM for AD
based on high-quality randomized controlled trials (RCTs) and reviewed its
possible mechanisms of neurogenesis according to animal-based researches. Twenty
eligible studies with 1767 subjects were identified in eight database searches
from inception to February 2017. The studies investigated the CHM versus placebo
(n=3), CHM versus donepezil (n=9 with 10 comparisons), CHM plus donepezil versus
donepezil (n=3), CHM versus a basic treatment (n=3), and CHM plus basic treatment
versus basic treatment (n=2). Adverse events were reported in 11 studies,
analyzed but not observed in 3 studies, and not analyzed in 6 studies. The main
findings of present study are that CHM as adjuvant therapy exerted an additive
anti-AD benefit, whereas the efficacy of CHM as a monotherapy was inconclusive.
Additionally, CHMs were generally safe and well tolerated in AD patients. Active
molecules in frequent constituents of CHMs can alter multiple critical signaling
pathways regulating neurogenesis. Thus, the present evidence supports, to a
limited extent, the conclusion that CHM can be recommended for routine use in AD
patients and its possible mechanism enhances adult hippocampal neurogenesis
through activating the multi-signal pathways.
PMID- 28690140
TI - New neurons in adult brain: distribution, molecular mechanisms and therapies.
AB - "Are new neurons added in the adult mammalian brain?" "Do neural stem cells
activate following CNS diseases?" "How can we modulate their activation to
promote recovery?" Recent findings in the field provide novel insights for
addressing these questions from a new perspective. In this review, we will
summarize the current knowledge about adult neurogenesis and neural stem cell
niches in healthy and pathological conditions. We will first overview the
milestones that have led to the discovery of the classical ventricular and
hippocampal neural stem cell niches. In adult brain, new neurons originate from
proliferating neural precursors located in the subventricular zone of the lateral
ventricles and in the subgranular zone of the hippocampus. However, recent
findings suggest that new neuronal cells can be added to the adult brain by
direct differentiation (e.g., without cell proliferation) from either quiescent
neural precursors or non-neuronal cells undergoing conversion or reprogramming to
neuronal fate. Accordingly, in this review we will also address critical aspects
of the newly described mechanisms of quiescence and direct conversion as well as
the more canonical activation of the neurogenic niches and neuroblast reservoirs
in pathological conditions. Finally, we will outline the critical elements
involved in neural progenitor proliferation, neuroblast migration and
differentiation and discuss their potential as targets for the development of
novel therapeutic drugs for neurodegenerative diseases.
PMID- 28690139
TI - 4-Aroyl-3-hydroxy-5-phenyl-1H-pyrrol-2(5H)-ones as N-formyl peptide receptor 1
(FPR1) antagonists.
AB - Formyl peptide receptors (FPRs) are expressed on a variety of leukocytes and play
important roles in inflammation. Thus, FPR antagonists may represent novel
therapeutics for modulating innate immunity and treating inflammatory diseases.
Previously, 1H-pyrrol-2(5H)-ones were reported to be potent and competitive FPR1
antagonists. In the present studies, 42 additional 1H-pyrrol-2(5H)-one analogs
were evaluated for FPR1 antagonist activity. We identified a number of novel
competitive FPR1 antagonists that inhibited N-formylmethionyl-leucyl
phenylalanine (fMLF)-induced intracellular Ca2+ mobilization in FPR1-transfected
HL60 cells and effectively competed with WKYMVm-FITC for binding to FPR1 in FPR1
transfected RBL cells. The most active pyrroles inhibited human neutrophil Ca2+
flux, chemotaxis, and adhesion to human epithelial cells, with the most potent
being compounds 14 (4-benzoyl-1-hexyl-3-hydroxy-5-(4-hydroxy-3-methoxyphenyl)-2,5
dihydro-1H-pyrrol-2-one) and 17 (4-benzoyl-5-(2,5-dimethoxyphenyl)-3-hydroxy-1-(2
methoxyethyl)-2,5-dihydro-1H-pyrrol-2-one). In addition, these FPR1 antagonists
inhibited fMLF-induced phosphorylation of extracellular signal-regulated kinases
(ERK1/2) in FPR1-RBL cells, differentiated HL-60 cells, and human neutrophils.
Most of the antagonists were specific for FPR1 and did not inhibit WKYMVM/WKYMVm
induced intracellular Ca2+ mobilization in FPR2-HL60 cells, FPR3-HL60 cells, or
interleukin 8-induced Ca2+ flux in human neutrophils. Moreover, molecular
modeling showed that the active pyrroles had a significantly higher degree of
similarity with the FPR1 antagonist pharmacophore template as compared to
inactive analogs. Thus, the 4-aroyl-3-hydroxy-5-phenyl-1H-pyrrol-2(5H)-one
scaffold represents an important backbone for the development of novel FPR1
antagonists and could provide important clues for understanding the molecular
structural requirements of FPR1 antagonists.
PMID- 28690141
TI - Molecular characterization and protein localization of the antimicrobial peptide
big defensin from the scallop Argopecten purpuratus after Vibrio splendidus
challenge.
AB - Big defensins are antimicrobial peptides (AMPs) that are proposed as important
effectors of the immune response in mollusks, chelicerates and chordates. At
present, only two members of the big defensin family have been identified in
scallop. In the present work, a cDNA sequence encoding a new big defensin
homologue was characterized from the scallop Argopecten purpuratus, namely ApBD1.
ApBD1 cDNA sequence comprised 585 nucleotides, with an open reading frame of 375
bp and 5'- and 3'-UTRs of 41 and 167 bp, respectively. The deduced protein
sequence contains 124 amino acids with a molecular weight of 13.5 kDa, showing
characteristic motifs of the big defensin family and presenting 76% identity with
the big defensin from the scallop A. irradians. Phylogenetic analysis revealed
that ApBD1 is included into the cluster of big defensins from mollusks. Tissue
specific transcript expression analysis by RT-qPCR showed that ApBD1 was present
in all tissues tested from non-immune challenged scallops but it was most
strongly expressed in the mantle. The transcript levels of ApBD1 were
significantly up-regulated in gills at 24 and 48 h post-injection with the heat
attenuated bacteria Vibrio splendidus. Additionally, immunofluorescence analysis
using a polyclonal anti-ApBD1 antibody showed that this protein was abundantly
located in epithelial linings of gills and mantle; and also in digestive gland
showing ApBD1-infiltrating hemocytes from immune challenged scallops. This is the
first time that a big defensin is detected and located at the protein level in a
mollusk. These results suggest an important role of ApBD1 in the mucosal immune
response of A. purpuratus.
PMID- 28690142
TI - Identification of an essential virulence gene of cyprinid herpesvirus 3.
AB - The genus Cyprinivirus consists of a growing list of phylogenetically related
viruses, some of which cause severe economic losses to the aquaculture industry.
The archetypal member, cyprinid herpesvirus 3 (CyHV-3) causes mass mortalities
worldwide in koi and common carp. A CyHV-3 mutant was described previously that
is attenuated in vivo by a deletion affecting two genes (ORF56 and ORF57). The
relative contributions of ORF56 and ORF57 to the safety and efficacy profile of
this vaccine candidate have now been assessed by analysing viruses individually
deleted for ORF56 or ORF57. Inoculation of these viruses into carp demonstrated
that the absence of ORF56 did not affect virulence, whereas the absence of ORF57
led to an attenuation comparable to, though slightly less than, that of the
doubly deleted virus. To demonstrate further the role of ORF57 as a key virulence
factor, a mutant retaining the ORF57 region but unable to express the ORF57
protein was produced by inserting multiple in-frame stop codons into the coding
region. Analysis of this virus in vivo revealed a safety and efficacy profile
comparable to that of the doubly deleted virus. These findings show that ORF57
encodes an essential CyHV-3 virulence factor. They also indicate that ORF57
orthologues in other cypriniviruses may offer promising targets for the rational
design of attenuated recombinant vaccines.
PMID- 28690144
TI - Preoperative long-course chemoradiotherapy plus adjuvant chemotherapy versus
short-course radiotherapy without adjuvant chemotherapy both with delayed surgery
for stage II-III resectable rectal cancer: 5-Year survival data of a randomized
controlled trial.
AB - BACKGROUND AND OBJECTIVE: At present, there are common recommendations for
treatment for stage II-III resectable rectal cancer patients: preoperative
conventional chemoradiotherapy (CRT) with delayed surgery in 6-8 weeks or
preoperative short-course radiotherapy (SCRT) followed by immediate surgery. The
aim of this study was to compare overall survival (OS) and disease-free survival
(DFS) in two treatment groups: preoperative SCRT and CRT both with delayed
surgery plus adjuvant chemotherapy in CRT arm. MATERIALS AND METHODS: A total of
150 patients were randomly assigned to two groups: 75 to CRT (preoperative
conventional CRT, 50Gy/25 fr with fluorouracil and leucovorin on the 1st and the
5th week of RT followed by TME surgery in 6-8 weeks and 4 cycles of adjuvant
fluorouracil/leucovorin every 4 weeks; then follow-up) and 75 to SCRT
(preoperative short-course RT, 25Gy/5 fr followed by TME surgery in 6-8 weeks;
then follow-up). The data of 140 patients (72 in CRT and 68 in SCRT group) were
included in statistical analysis. Primary end points were OS and DFS. RESULTS:
Median follow-up was 60.5 (range, 5-108) months. The 5-year DFS was 67% in the
CRT group (n=72) and 45% in the SCRT group (n=68) (P=0.013; HR=1.88; 95% CI, 1.13
3.12; P=0.015). The 5-year OS was 79% and 62% in the CRT and SCRT groups,
respectively (P=0.015; HR=2.05; 95% CI, 1.13-3.70; P=0.017). The 5-year OS for
intent-to-treat (ITT) population (n=150) was 78% in the CRT and 58% in the SCRT
group (P=0.003; HR=2.28; 95% CI, 1.30-4.00; P=0.004). CONCLUSIONS: The 5-year DFS
and OS were significantly better in the CRT than the SCRT group. For ITT
population, OS was also significantly better after CRT versus SCRT.
PMID- 28690143
TI - The brain-penetrant 5-HT7 receptor agonist LP-211 reduces the sensory and
affective components of neuropathic pain.
AB - Neuropathic pain is a debilitating pathological condition of high clinical
relevance. Changes in neuronal excitability in the anterior cingulate cortex
(ACC) play a central role in the negative emotional and affective aspects of
chronic pain. We evaluated the effects of LP-211, a new serotonin-receptor-type-7
(5-HT7R) agonist that crosses the blood-brain barrier, on ACC neurons in a mouse
model of neuropathic pain. LP-211 reduced synaptic integration in layer 5
pyramidal neurons, which was enhanced in neuropathic pain due to a dysfunction of
dendritic hyperpolarization-activated-and-cyclic-nucleotide-regulated (HCN)
channels. Acute injection of LP-211 had an analgesic effect, increasing the
mechanical withdrawal threshold in neuropathic animals, which was partially
mediated by an action in the ACC. Additionally, the acute application of LP-211
blocked the switch in the place escape/avoidance behavior induced by noxious
stimuli. Thus systemic treatment with a 5-HT7R agonist leads to modulation of the
ACC, which dampens sensory and affective aspects of chronic pain.
PMID- 28690145
TI - Salivary gland transcripts of the kissing bug, Panstrongylus chinai, a vector of
Chagas disease.
AB - The saliva of hematophagous arthropods injected during blood feeding contains
potent pharmacologically active components to counteract the host hemostatic and
inflammatory systems. In the present study, dominant salivary gland transcripts
of Panstrongylus chinai, a vector of Chagas disease, were analyzed by sequencing
randomly selected clones of the salivary gland cDNA library. This analysis showed
that 56.5% of the isolated transcripts coded for putative secreted proteins, of
which 73.7% coded for proteins belonging to the lipocalin family. The most
abundant transcript of lipocalin family proteins was a homologue of pallidipin 2,
an inhibitor of collagen-induced platelet aggregation of Triatoma pallidipennis.
In addition, homologues of triafestin, an inhibitor of the kallikrein-kinin
system of T. infestans, were identified as the dominant transcript. Other
salivary transcripts encoding lipocalin family proteins had homology to triplatin
(an inhibitor of platelet aggregation) and others with unknown function. Other
than lipocalin family proteins, homologues of a Kazal-type serine protease
inhibitor (putative anticoagulant), a hemolysin-like protein (unknown function),
inositol polyphosphate 5-related protein (a regulator of membrane
phosphoinositide), antigen 5-related protein (unknown function) and apyrase
(platelet aggregation inhibitor) were identified.
PMID- 28690146
TI - Asian genotype of Chikungunya virus circulating in Venezuela during 2014.
AB - Chikungunya virus emerged on Saint-Martin Island in the Caribbean in late 2013.
Since then in July of 2104 Venezuela reported autochthonous cases. This study
reports the first phylogenetic characterization of CHIKV autochthonous cases in
Venezuela, 2014. The phylogenetic analysis showed that the CHIKV circulating in
Venezuela (Aragua state) belong to the Asian genotype (Caribbean clade) and it is
related to viruses that circulated in the same year in the Caribbean.
PMID- 28690147
TI - Novel Anaplasma and Ehrlichia organisms infecting the wildlife of two regions of
the Brazilian Amazon.
AB - During 2009-2012, wild animals were sampled in the Amazon biome of Brazil. Animal
tissues and blood were tested by polymerase chain reaction (PCR) assays targeting
DNA of the bacterial family Anaplasmataceae (genera Anaplasma, Ehrlichia,
Wolbachia) and the genus Borrelia. Overall, 181 wild animals comprising 36
different species (2 reptiles, 5 birds, and 29 mammals) were sampled. All birds
and reptiles were negative by all PCR assays, as well as all mammals for the
Borrelia PCR assay. Anaplasmataceae agents were searched by PCR assays targeting
two different genes, the ribosomal 16S rRNA gene and the protein-coding dsb gene.
Three dsb closely related haplotypes were generated from 3 white-lipped peccaries
(Tayassu pecari). In a phylogenetic analysis inferred from dsb partial sequences,
these haplotypes grouped with previously reported Ehrlichia haplotypes from
jaguar (Panthera onca) and horse from Brazil, suggesting that they could all
represent a single species, yet to be properly characterized. A unique dsb
haplotype was generated from a sloth (Bradypus tridactylus), and could also
represent a different Ehrlichia species. All these dsb haplotypes formed a clade
sister to the Ehrlichia ruminantium clade. Three distinct 16S rRNA gene
haplotypes were generated from a wild guinea pig (Cavia sp.), a woolly mouse
opossum (Micoureus demerarae), and two from robust capuchin monkeys (Sapajus
sp.). In a phylogenetic analysis inferred from 16S rRNA gene partial sequence,
these haplotypes grouped within the Wolbachia clade, and are likely to represent
Wolbachia organisms that were infecting invertebrate metazoarians (e.g.,
filarids) associated with the sampled mammals. Two deer (Mazama americana)
samples yielded two distinct 16S rRNA gene sequences, one identical to several
sequences of Anaplasma bovis, and an unique sequence that grouped in a clade with
different Anaplasma species. Our results indicate that a variety of genetically
distinct Anaplasmataceae organisms, including potentially new Ehrlichia species,
circulate under natural conditions in the Amazonian wildlife.
PMID- 28690148
TI - Betulinic acid induces cell death by necrosis in Trypanosoma cruzi.
AB - Chagas' disease is a neglected disease caused by the protozoan parasite
Trypanosoma cruzi and constitutes a serious health problem worldwide. The
treatment is limited, with variable efficacy of benznidazole and nifurtimox.
Betulinic Acid (BA), a triterpene, can be found in medicinal herbs and has a wide
variety of biological and pharmacological activities. The objective was to
evaluate betulinic acid effects on the cell death mechanism in Trypanosoma cruzi
strain Y. BA inhibited the growth of epimastigotes in periods of 24h
(IC50=73.43MUM), 48h (IC50=119.8MUM) and 72h (IC50=212.2MUM) of incubation; of
trypomastigotes (IC50=51.88MUM) in periods of 24h and intracellular amastigotes
(IC50=25.94MUM) in periods of 24 and 48h of incubation, no toxicity on LLC-MK2
cells at the concentrations used. Analysis of the possible mechanism of parasite
cell death showed alterations in mitochondrial membrane potential, alterations in
cell membrane integrity, an increase in the formation of reactive oxygen species
and increase swelling of the reservosomes. In conclusion, betulinic acid was be
able to inhibition all developmental forms of Trypanosoma cruzi Y strain with
necrotic mechanism and involvement of mitochondrial membrane potential alteration
and increase in reactive oxygen species.
PMID- 28690149
TI - Creating a 'social zeitgeber' to synchronize family emotional rhythms: A new
therapeutic approach in child and adolescent psychiatry.
AB - A family can be viewed as a system respecting the principle of homeostasis and
therefore considered as a system in equilibrium or out of equilibrium, or even
both simultaneously or consecutively. Within a family system, there are
oscillatory phenomena and synchronization of the emotional, behavioral and
relational rhythms of each member of the family system as well as synchronization
of this system with others. A disruption of family synchronies, consisting of
successive desynchronizations and resynchronizations, can take place in order for
a change to occur. We created a mobile team for preadolescents and adolescents
with psychological difficulties and their families; this mobile team enables to
trigger a change by acting on the family synchronies like a 'social zeitgeber',
i.e. an external factor synchronizing social and biological rhythms. The mobile
team acts by disrupting the synchronies of the family system and this disruption
is facilitated by a state of crisis experienced by the family. More specifically,
the mobile team intervention provokes changes in the family representations
associated with changes in the family emotional climate, measured by expressed
emotion, due to disruptions in the synchronization of certain rhythms
(desynchronization and then resynchronization of these rhythms), and could
therefore be considered as a 'social zeitgeber'. It creates an experience that
becomes part of the individual's and family's history and could be reactivated in
the future if necessary. Finally, it allows the family and the adolescent with
difficulties to reach new perspectives and representations which participates to
the process of change, but also to benefit at the same time from a secure basis
and frame created by the (re)synchronization of family emotions through the
intervention of the mobile team following a ritualized procedure.
PMID- 28690150
TI - Serotonin induces ecdysteroidogenesis and methyl farnesoate synthesis in the mud
crab, Scylla serrata.
AB - In the current study, we have examined the role of serotonin in regulating the
levels of methyl farnesoate and ecdysteroids in the giant mud crab Scylla serrata
and validated that serotonin indeed is a reproductive hormone. Administration of
serotonin elevated circulatory levels of methyl farnesoate and ecdysteroids in
crabs. Since methyl farnesoate and ecdysteroid act through retinoid X receptor
(RXR) and ecdysteroid receptor (EcR) respectively and these receptors are
involved in the regulation of reproduction in crustaceans, we have determined the
mRNA levels of RXR and EcR in hepatopancreas and ovary after serotonin
administration. The expression levels of both RXR and EcR increased significantly
in the hepatopancreas and ovary of serotonin injected crabs when compared to the
controls. In vitro organ culture studies revealed that incubation of Y-orgas and
mandibular organ explants in the presence of serotonin resulted in a significant
increase in the secretion of ecdysteroids by Y-organs, but without alterations in
MF synthesis in mandibular organs. From the above studies it is evident that
serotonin stimulates Y organs resulting in increased ecdysteroidogenesis. Though
the circulatory levels methyl farnesoate elevated after serotonin administration,
organ culture studies revealed serotonin mediated methyl farnesaote synthesis is
indirect probably by inhibiting release of mandibular organ inhibiting hormone
from eyestalks.
PMID- 28690151
TI - Identification of STS-1 as a novel ShcA-binding protein.
AB - ShcA is a cytoplasmic signaling protein that supports signal transduction by
receptor protein-tyrosine kinases by providing auxiliary tyrosine phosphorylation
sites that engage additional signaling proteins. The principal binding partner
for tyrosine phosphorylation sites on ShcA is Grb2. In the current study, we have
used phosphotyrosine-containing peptides to isolate and identify STS-1 as a novel
ShcA-binding protein. Our results further show that the interaction between STS-1
and ShcA is regulated in response to EGF receptor activation.
PMID- 28690152
TI - Decreased expression of orexin 1 receptor in adult mice testes during alloxan
induced diabetes mellitus perturbs testicular steroidogenesis and glucose
homeostasis.
AB - Diabetes mellitus (DM) affects male reproductive system and causes infertility.
The male reproductive health is largely dependent upon uptake and proper
utilization of glucose by testicular cells. Results show involvement of orexin A
(OXA) and its receptor (OX1R) in regulation of steroidogenesis and glucose
homeostasis in adult mice testis. However, the role of OX1R in regulation of
testicular functions during hyperglycemia has not been investigated so far. The
present study, therefore, examined the role of OX1R in regulation of
steroidogenesis and glucose homeostasis in testis of adult mice during alloxan
induced type 1 DM. A significant decrease was noted in body weight and testis
weight in alloxan-treated mice compared to controls. The blood glucose level,
however, was markedly increased in treated animals than in controls. Further,
serum and intratesticular level of testosterone, activities of testicular
steroidogenic enzymes, and expressions of various steroidogenic markers, OX1R,
glucose transporter 3 (GLUT3) and Wilms' tumor gene (WT1) were downregulated in
treated mice. The level of glucose, activity of lactate dehydrogenase (LDH) and
lactate concentration in the testes of diabetic mice were also decreased; a
significant increase in the number of testicular apoptotic cells with concomitant
increase in the expression of caspase-3 was noted in these mice. Furthermore, DM
affected germ cell proliferation with decreased expression of proliferating cell
nuclear antigen (PCNA). Results thus suggest that type 1 DM impairs testicular
steroidogenesis and glucose homeostasis through inhibition of OXA/OX1R signaling
cascade due to decreased OX1R expression in adult mice, thereby affecting germ
cell survival and their proliferation in the testis.
PMID- 28690153
TI - Membrane-localized ubiquitin ligase ATL15 functions in sugar-responsive growth
regulation in Arabidopsis.
AB - Ubiquitin ligases play important roles in regulating various cellular processes
by modulating the protein function of specific ubiquitination targets. The
Arabidopsis Toxicos en Levadura (ATL) family is a group of plant-specific RING
type ubiquitin ligases that localize to membranes via their N-terminal
transmembrane-like domains. To date, 91 ATL isoforms have been identified in the
Arabidopsis genome, with several ATLs reported to be involved in regulating plant
responses to environmental stresses. However, the functions of most ATLs remain
unknown. This study, involving transcriptome database analysis, identifies ATL15
as a sugar responsive ATL gene in Arabidopsis. ATL15 expression was rapidly down
regulated in the presence of sugar. The ATL15 protein showed ubiquitin ligase
activity in vitro and localized to plasma membrane and endomembrane compartments.
Further genetic analyses demonstrated that the atl15 knockout mutants are
insensitive to high glucose concentrations, whereas ATL15 overexpression
depresses plant growth. In addition, endogenous glucose and starch amounts were
reciprocally affected in the atl15 knockout mutants and the ATL15 overexpressors.
These results suggest that ATL15 protein plays a significant role as a membrane
localized ubiquitin ligase that regulates sugar-responsive plant growth in
Arabidopsis.
PMID- 28690154
TI - Overexpression of a novel MYB-related transcription factor, OsMYBR1, confers
improved drought tolerance and decreased ABA sensitivity in rice.
AB - The MYB proteins play important roles in regulating plant responses to
environmental stresses. We cloned and functionally characterized a novel MYB
related gene, OsMYBR1, from rice. Our microarray and qRT-PCR analyses showed that
its expression was induced by drought and cold in different tissues at various
developmental stages. This gene encodes a putative MYB-related protein of 463
amino acid residues. Compared with wild-type (WT) plants, transgenic plants over
expressing OsMYBR1 exhibited much greater tolerance to drought stress and
decreased sensitivity to abscisic acid (ABA). Under drought treatment, levels of
free proline and soluble sugar were higher in transgenic plants than in the WT.
Furthermore, transcriptional expression of four stress-related genes -- OsP5CS1,
OsProt, OsLEA3, and OsRab16 -- was significantly increased in transgenic plants
under drought stressed conditions and ABA. Our results provide evidence that
OsMYBR1 is involved in mediating plant responses to ABA and drought.
PMID- 28690155
TI - Plant breeding as the cornerstone of a sustainable bioeconomy.
AB - A prime driver for a bioeconomy is the need to ensure the availability of
sufficient biomass feedstock for food, feed, energy and industrial uses. This
demand must be properly managed in the face of several challenges, including
environmental changes and abrupt climate shifts. Plant breeding and breeding
innovation is the cornerstone for sustainable supply of biomass. Not only does
research and development in this sector aim at providing high yielding crops in
order to maximize production, but R&D in this field will also allow to obtain
highly specialized plant varieties with new or improved traits that fit to
specific applications. At the same time, there is little awareness among the
general public of the fact that state-of-the-art R&D is a prerequisite for the
production of sufficient biomass of the right quality in a sustainable manner.
Plant breeders in the EU have to grapple with a rather challenging policy and
regulatory framework. An important way forward to overcome the existing impasse
would be to ensure transparent and trustworthy communication with the general
public.
PMID- 28690156
TI - The microbiome as engineering tool: Manufacturing and trading between
microorganisms.
AB - The integration of microbial technologies within the framework of the water
energy nexus has been taking place for over a century, but these mixed microbial
communities are considered hard to deal with 'black boxes'. Process steering is
mainly based on avoiding process failure by monitoring conventional parameters,
e.g., pH and temperature, which often leads to operation far below the intrinsic
potential. Mixed microbial communities do not reflect a randomised individual
mix, but an interacting microbiological entity. Advance monitoring to obtain
effective engineering of the microbiome is achievable, and even crucial to obtain
the desired performance and products. This can be achieved via a top-down or
bottom-up approach. The top-down strategy is reflected in the microbial resource
management concept that considers the microbial community as a well-structured
network. This network can be monitored by means of molecular techniques that will
allow the development of accurate and quick decision tools. In contrast, the
bottom-up approach makes use of synthetic cultures that can be composed starting
from defined axenic cultures, based on the requirements of the process under
consideration. The success of both approaches depends on real-time monitoring and
control. Of particular importance is the necessity to identify and characterise
the key players in the process. These key players not only relate with the
establishment of functional conversions, but also with the interaction between
partner bacteria. This emphasises the importance of molecular (screening)
techniques to obtain structural and functional insights, minimise energy input,
and maximise product output by means of integrated microbiome processes.
PMID- 28690157
TI - Cell-free protein synthesis in micro compartments: building a minimal cell from
biobricks.
AB - The construction of a minimal cell that exhibits the essential characteristics of
life is a great challenge in the field of synthetic biology. Assembling a minimal
cell requires multidisciplinary expertise from physics, chemistry and biology.
Scientists from different backgrounds tend to define the essence of 'life'
differently and have thus proposed different artificial cell models possessing
one or several essential features of living cells. Using the tools and methods of
molecular biology, the bottom-up engineering of a minimal cell appears in reach.
However, several challenges still remain. In particular, the integration of
individual sub-systems that is required to achieve a self-reproducing cell model
presents a complex optimization challenge. For example, multiple self
organisation and self-assembly processes have to be carefully tuned. We review
advances and developments of new methods and techniques, for cell-free protein
synthesis as well as micro-fabrication, for their potential to resolve challenges
and to accelerate the development of minimal cells.
PMID- 28690158
TI - Continuous volatile fatty acid production from lignocellulosic biomass by a novel
rumen-mimetic bioprocess.
AB - Lignocellulosic biomass is an attractive source of biofuels and biochemicals,
being abundant in various plant sources. However, processing this type of biomass
requires hydrolysis of cellulose. The proposed rumen-mimetic bioprocess consists
of dry-pulverization of lignocellulosic biomass and pH-controlled continuous
cultivation of ruminal bacteria using ammonium as a nitrogen source. In this
study, ruminal bacteria were continuously cultivated for over 60 days and used to
digest microcrystalline cellulose, rice straw, and Japanese cedar to produce
volatile fatty acids (VFAs). The ruminal bacteria grew well in the chemically
defined medium. The amounts of VFAs produced from 20 g of cellulose, rice straw,
and Japanese cedar were 183 +/- 29.7, 69.6 +/- 12.2, and 21.8 +/- 12.9 mmol,
respectively. Each digestion completed within 24 h. The carbon yield was 60.6%
when 180 mmol of VFAs was produced from 20 g of cellulose. During the
cultivation, the bacteria were observed to form flocs that enfolded the feed
particles. These flocs likely contain all of the bacterial species necessary to
convert lignocellulosic biomass to VFAs and microbial protein symbiotically.
Denaturing gradient gel electrophoresis (DGGE) analysis of PCR-amplified 16S rDNA
fragments revealed that the bacterial community was relatively stable after 1
week in cultivation, though it was different from the original community
structure. Furthermore, sequence analysis of the DGGE bands indicates that the
microbial community includes a cellulolytic bacterium, a bacterium acting
synergistically with cellulolytic bacteria, and a propionate-producing bacterium,
as well as other anaerobic bacteria.
PMID- 28690159
TI - Probiotic-mediated blueberry (Vaccinium corymbosum L.) fruit fermentation to
yield functionalized products for augmented antibacterial and antioxidant
activity.
AB - The aim of this study was to investigate the fermentation of blueberry fruit with
selected probiotic bacteria (Bacillus amyloliquefaciens and Lactobacillus brevis)
and yeast (Starmerella bombicola) isolated from fermented starfish for the
extraction of functionalized products for biomedical applications. All probiotic
based fermented extracts showed augmented antibacterial and antioxidant activity
compared to the control. Biochemical parameters of viable cell count, titratable
acidity, total phenol, total anthocyanin, total flavonoids, total sugar, and
reducing sugar were analyzed during a 0-96 h fermentation period. In addition,
Fourier transform infrared (FTIR) spectroscopy was performed to determine the
functional groups in the control and fermented extracts and it signifies the
presence of alcohol groups, phenol groups, carboxylic acids, and aliphatic
amines, respectively. The well diffusion, minimum inhibitory concentration (MIC),
and minimum bactericidal concentration (MBC) assays determined that the S.
bombicola-mediated fermented extract has excellent activity, followed by B.
amyloliquefaciens and L. brevis, at a high concentration of 1.0 g/mL fermented
extract. The ABTS and DPPH showed significant scavenging activity with IC50
values of (30.52 +/- 0.08)/(155.10 +/- 0.06) MUg/mL, (24.82 +/- 0.16)/(74.21 +/-
1.26) MUg/mL, and (21.81 +/- 0.08)/(125.11 +/- 0.04) MUg/mL for B.
amyloliquefaciens, L. brevis, and S. bombicola, respectively. Developing a value
added fermented blueberry product will help circumvent losses because of the
highly perishable nature of the fruit.
PMID- 28690161
TI - Ultrasound targeted CNS gene delivery for Parkinson's disease treatment.
AB - Parkinson's disease (PD) is a potent neurodegenerative disease in which a
progressive loss of dopaminergic neurons eventually produces a loss of movement
control and other symptoms. To date, in addition to pharmacological, non
pharmacological, and neurosurgical therapies, gene delivery has emerged as a
potential therapeutic modality for PD. Effective targeted gene delivery is
complicated in that gene vectors cannot penetrate the blood-brain barrier (BBB),
thus clinical tests must rely on invasive intracerebral gene vector injection.
Burst low-pressure focused ultrasound exposure with microbubbles has been
demonstrated to noninvasively target and temporally open the BBB, opening new
opportunities to transport large molecule substances into the brain for central
nervous system (CNS) disease treatment, and raising the potential for noninvasive
gene delivery for PD treatment. This paper reviews the underlying mechanism and
current progress for focused ultrasound induced CNS gene delivery, and summarizes
potential directions for further ultrasound-medicated PD gene therapy.
PMID- 28690160
TI - Polymer conjugated retinoids for controlled transdermal delivery.
AB - All-trans retinoic acid (ATRA), a derivative of vitamin A, is a common component
in cosmetics and commercial acne creams as well as being a first-line
chemotherapeutic agent. Today, formulations for the topical application of ATRA
rely on creams and emulsions to incorporate the highly hydrophobic ATRA drug.
These strategies, when applied to the skin, deliver ATRA as a single bolus, which
is immediately taken up into the skin and contributes to many of the known
adverse side effects of ATRA treatment, including skin irritation and hair loss.
Herein we present a new concept in topical delivery of retinoids by covalently
bonding the drug through a hydrolytically degradable ester linkage to a common
hydrophilic polymer, polyvinyl alcohol (PVA), creating an amphiphilic
nanomaterial that is water-soluble. This PVA bound ATRA can then act as a pro
drug and accumulate within the skin to allow for the sustained controlled
delivery of active ATRA. This approach was demonstrated to release active ATRA
out to 10days in vitro while significantly enhancing dermal accumulation of the
ATRA in explant pig skin. In vivo we demonstrate that the pro-drug formulation
reduces application site inflammation compared to free ATRA and retains the drug
at the application site at measurable quantities for up to six days.
PMID- 28690162
TI - National guidelines on screening for diabetes among patients with tuberculosis in
India: Need for clarity and change in screening cut off?
PMID- 28690163
TI - Relationship between metabolic syndrome and osteoarthritis: The Fasa
Osteoarthritis Study.
AB - BACKGROUND: An association between metabolic syndrome (MeS) and osteoarthritis
(OA) has been reported in recent years; however, conflicting findings have been
reported regarding this matter. Inhere we evaluated the relationship between
different components of MeS and OA in a Fasa osteoarthritis registry (FOAS).
METHODS: The registry includes all OA cases who referred to Fasa hospital (Iran)
since 2013. Overall, 131 patients with OA with a Kellgren & Lawrence (K&L) score
>1 and 261 controls were compared. RESULTS: Overall, 82.4% of individuals in the
OA group and 40.8% of participants in the control group had MeS (P<0.001).
Patients with OA had a 6.8 (95% CI: 4.1-11.4) higher chance of acquiring MeS.
After adjusting for sex, age, and BMI, odds' ratio (OR) for acquiring MeS in OA
group increased to 10.9 (95% CI: 5.5-21.8). Among MeS criteria's, high waist
circumference (WC) has strongest correlation for acquiring OA (OR=27.535, 95% CI:
6.003-126.306). CONCLUSION: Our findings revealed that metabolic markers are
strongly associated with OA and the addition of each component of the MeS,
significantly increases the risk of developing OA, therefore control of metabolic
factors and appropriate screening must be considered in health policy making and
prevention programs.
PMID- 28690164
TI - Effect of degree of deacetylation of chitosan on adsorption capacity and
reusability of chitosan/polyvinyl alcohol/TiO2 nano composite.
AB - The chitosan/polyvinyl alcohol/TiO2 composite was synthesized. Two different
degrees of deacetylation of chitosan were prepared by hydrolysis to compare the
effectiveness of them. The composite was analyzed via field emission scanning
electron microscopy, Fourier transform infrared, X-ray diffraction, thermal
gravimetric analysis, weight loss test and adsorption study. The FTIR and XRD
results proved the interaction among chitosan, PVA and TiO2 without any chemical
reaction. It was found that, chitosan with higher degree of deacetylation has
better stability. Furthermore, it also showed that higher DD of chitosan required
less time to reach equilibrium for methyl orange. The adsorption followed the
pseudo-second-order kinetic model. The Langmuir and Freundlich isotherm models
were fitted well for isotherm study. Adsorption capacity was higher for the
composite containing chitosan with higher DD. The dye removal rate was
independent of the dye's initial concentration. The adsorption capacity was
increased with temperature and it was found from reusability test that the
composite containing chitosan with higher DD is more reusable. It was notable
that adsorption capacity was even after 15 runs. Therefore, chitosan/PVA/TiO2
composite can be a very useful material for dye removal.
PMID- 28690165
TI - p53, MAPKAPK-2 and caspases regulate nickel oxide nanoparticles induce cell death
and cytogenetic anomalies in rats.
AB - The unique properties of nickel oxide nanoparticles (NiO-NPs) distinguish it from
traditional nickel containing materials, and enable its industrial application as
an advanced nanomaterial. Despite the benefits, the in vivo toxicological studies
on NiO-NPs have been mainly focused on its pulmonary pathology. However, NiO-NPs
exposure via oral route and its subsequent toxic effects in exposed animals are
still lacking. Hence, we evaluated the NiO-NPs oral toxicity in male Wistar rats.
NiO-NPs induced significant increase in chromosomal aberrations (CAs),
micronuclei (MN) formation and, DNA damage in rats. Flow cytometric analysis
showed apoptosis, ROS generation and dysfunction of mitochondrial membrane
potential (DeltaPsim). Imbalance of antioxidant enzymes, along with histological
alterations was found in liver. Taking together, these results unequivocally
suggested that NiO-NPs induced toxicity was through cyto-genetic alterations,
oxidative stress, apoptosis and liver toxicity. The western blotting data
validated the interplay of p53 and MAPKAPK-2 signalling via activation of
caspases 8, 3, cyto c, pro-apoptotic bax and anti-apoptotic bcl-2 proteins.
PMID- 28690166
TI - Immune response of anti-lectin Pjlec antibody in freshwater crab Paratelphusa
jacquemontii.
AB - Sialic acid specific lectin Pjlec isolated from serum of the freshwater crab
Paratelphusa jacquemontii served as an antigen for the production of
immunoglobulin (Ig) in Balb/c mice sera. Enzyme-linked immunosorbent assay
(ELISA) of mice anti-sera with Pjlec lectin affirmed the induction and production
of antibody. Anti-Pjlec antibody was isolated from the antisera of mice by
Protein A Sepharose affinity chromatography and checked for purity by immunoblot
with lectin. Mass spectrometry (MS/MS) of papain digethe peptide sequence of
antigen binding fragment (Fab) and fragment crystallizable (Fc). Coatingsted anti
Pjlec revealed of anti-Pjlec to the target cell, rabbit erythrocyte failed to
enhance in vitro phagocytosis in the crab. However, inoculation of anti-Pjlec in
the hemolymph of the crab elicited in vitro phagocytosis. Proteins in hemocyte
lysate supernatant (HLS) were separated by electrophoresis failed to immunoblot
with Pjlec or anti-Pjlec. Peptide sequences of trypsin digested lectin protein
appeared homologous to deuterostome chordate. The protostome crab that lack the
ability to synthesize sialic acid however bind to sialic acid a deuterostome
sugar to suggest the complexity in innate immune system of invertebrates. The
application of lectin and its antibody require further study on application of
pathological conditions associated with alterations in sialylated cell surface.
PMID- 28690167
TI - Evaluation of lignins from side-streams generated in an olive tree pruning-based
biorefinery: Bioethanol production and alkaline pulping.
AB - In modern lignocellulosic-based biorefineries, carbohydrates can be transformed
into biofuels and pulp and paper, whereas lignin is burned to obtain energy.
However, a part of lignin could be converted into value-added products including
bio-based aromatic chemicals, as well as building blocks for materials. Then, a
good knowledge of lignin is necessary to define its valorisation procedure. This
study characterized different lignins from side-streams produced from olive tree
pruning bioethanol production (lignins collected from steam explosion
pretreatment with water or phosphoric acid as catalysts, followed by simultaneous
saccharification and fermentation process) and alkaline pulping (lignins
recovered from kraft and soda-AQ black liquors). Together with the chemical
composition, the structure of lignins was investigated by FTIR, 13C NMR, and 2D
NMR. Bioethanol lignins had clearly distinct characteristics compared to pulping
lignins; a certain number of side-chain linkages (mostly alkyl-aryl ether and
resinol) accompanied with lower phenolic hydroxyls content. Bioethanol lignins
also showed a significant amount of carbohydrates, mainly glucose and protein
impurities. By contrast, pulping lignins revealed xylose together with a
dramatical reduction of side-chains (some resinol linkages survive) and thereby
higher phenol content, indicating rather severe lignin degradation during
alkaline pulping processes. All lignins showed a predominance of syringyl units.
PMID- 28690168
TI - PEGylation of cytochrome P450 enhances its biocatalytic performance for pesticide
transformation.
AB - Pesticide intoxication is a major public health concern, and unfortunately there
is not an effective treatment for severe organophosphorus pesticide intoxication.
In this work, a non-immunogenic enzymatic bioconjugate based on cytochrome P450
was assayed for organophosphorus pesticide transformation. Enzyme therapy is an
alternative approach to inactivate pesticides in the bloodstream, transforming
them into less toxic metabolites. A variant of cytochrome P450 (CYPBM3 F87A) from
Bacillus megaterium was chemically modified with polyethylene glycol. The
PEGylated enzyme showed enhanced pesticide transformation activity when compared
with the unmodified protein. The transformation rates were higher than those
obtained with the unmodified enzyme for all six pesticides transformed. The
specific activity of PEGylated preparation for parathion and dichlorophen was up
to 9-times higher than these obtained with the unmodified enzyme. In addition,
the modified CYP (CYP-PEG) remained active at extremely high pHs, maintaining 90%
of its maximal activity at pH 11, as opposed to the unmodified CYP that retained
less than 20% of its maximal activity at that pH. In addition, the bioconjugate
showed good catalytic activity in blood serum and innocuousness on immune cells.
The potential use of PEGylated CYP as a detoxification strategy for pesticide
poisoning is demonstrated and discussed.
PMID- 28690169
TI - Unraveling the thermodynamics, binding mechanism and conformational changes of
HSA with chromolyn sodium: Multispecroscopy, isothermal titration calorimetry and
molecular docking studies.
AB - Cromolyn sodium is an anti-allergic drug effective for treatment in asthma and
allergic rhinitis. In this project, interaction of chromolyn sodium (CS) with
human serum albumin (HSA) has been investigated by various techniques such as UV
vis, fluorescence, circular dichorism (CD), fourier transform infrared (FT-IR)
spectroscopy, isothermal titration calorimetric (ITC) and molecular docking. The
fluorescence quenching results revealed that there was static quenching mechanism
in the interactions of CS with HSA. The binding constant (Kb), enthalpy change
(DeltaH degrees ), entropy change (DeltaS degrees ) and Gibbs free energy change
(DeltaG degrees ) were calculated. The negative values of TDeltaS degrees and
DeltaH degrees obtained from fluorescence spectroscopy and isothermal titration
calorimetry, indicate that hydrogen bonding and van der Waal's forces played
major role in the binding process and the reaction is exothermic in nature. The
binding constant (Kb) was found to be in the order of 104M-1 which depicts a good
binding affinity of CS towards HSA. The conformational changes in the HSA due to
interaction of CS were investigated from CD and FT-IR spectroscopy. The binding
site of CS in HSA was sub-domain IIA as evident from site probing experiment and
molecular docking studies.
PMID- 28690170
TI - Polyhydroxybutyrate by Streptomyces sp.: Production and characterization.
AB - A total number of 20 actinomycetes isolates were isolated from soil sediments
obtained from Semmancheri coastal areas of Bay of Bengal, India and they were
qualitatively screened for the production of polyhydroxybutyrate (PHB) on a
medium containing Sudan black stain. Nine of the 20 isolates produced PHB and the
quantity of PHB produced varied from 1.79 to 4.26g-L. Among the positive isolates
an actinomycete isolate which was identified as Streptomyces sp. through 16S rRNA
sequencing analysis (Accession No: KF667247) produced relatively higher PHB than
other positive isolates. Subsequently, the growth conditions were optimized for
the maximum PHB production by the chosen organism. Attempt was also made to
utilize natural carbon sources such as paddy straw, wheat bran, rice bran,
sugarcane molasses and oil cake for the production of PHB in an attempt to reduce
the cost production of PHB. The purified PHB was analyzed by Solid-State 13C NMR,
Fourier Transformed Infrared spectroscopy, Powder X-ray diffraction,
Thermogravimetric Analysis, Scanning and Transmission Electron Microscopic
analyses to determine the structure, crystallinity, purity and thermal stability.
The present investigation has revealed that Streptomyces sp. could be a potential
source for the production of PHB with desirable characteristics and could also be
exploited for the industrial production.
PMID- 28690171
TI - A fucoidan fraction purified from Chnoospora minima; a potential inhibitor of LPS
induced inflammatory responses.
AB - Fucoidans are an interesting group of bioactive sulfated polysaccharides abundant
in brown seaweeds. The current study highlights the enrichment and extraction of
fucoidan from Chnoospora minima by means of enzyme-assistant extraction using
Celluclast and evaluation of its anti-inflammatory potential through in vitro and
in vivo studies. The purified C. minima fucoidan (F2,4) inhibited the nitrous
oxide (NO) production (IC50=27.82+/-0.88MUg/ml) and expression of PGE2 through
the subsequent downregulation of iNOS and COX-2 expression in lipopolysaccharide
(LPS) stimulated RAW 264.7 macrophages. F2,4 downregulated TNF-alpha, IL1-beta,
and IL-6 in RAW 264.7 macrophages in a dose-dependent manner and suppressed NO
and ROS production in LPS stimulated zebrafish embryos while exerting a
protective effect against the cell damage caused by LPS. Polysaccharide
structural characterization was performed using FTIR, HPAE-PAD analysis of the
monosaccharide content and NMR spectroscopy. Current findings confirm the
potential anti-inflammatory activity of fucoidan purified from C. minima and
elaborate its potential application as a functional ingredient in consumer
products.
PMID- 28690172
TI - Managing colonic inflammation associated gut derangements by systematically
optimised and targeted ginger extract-Lactobacillus acidophilus loaded
pharmacobiotic alginate beads.
AB - Presently, we explore a cobiotic-ginger extract (GE; antioxidant
antiinflammatory) and Lactobacillus acidophilus (LAB, probiotic), for control of
oxidative-stress, inflammation and dysbiosis mediated gut ailments. Since orally
administered LAB looses viability while GE is a gastric irritant with poor ADME,
we encapsulated them into calcium-alginate beads. Water-loving, viscolysing, and
osmotic-building effects of polyethylene glycol were used to address poor
probiotic encapsulation (<=10%) by effective sealing of numerous fine voids
formed in the alginate gel. Beads were systematically optimized for maximum
entrapment (92+/-2.3% for GE, and 30+/-1.2% for LAB) and sustained release, and
were coated with eudragit-S100 for colonic-targetability, as established by in
vitro release. In-vivo evaluation in DMH-DSS induced colitis and precancerous
lesions, in rats, indicated attenuation of oxidative stress (catalase, SOD, LPO)
and inflammatory burden (IL-6 and TNF-alpha), and downregulation of COX-2, iNOS,
and c-Myc by both GE and LAB; restoration of colonic permeability by GE; and
modulation of gut bacteria and SCFAs by LAB as the mechanisms of action.
Complementing activities of GE and LAB in cobiotic beads lead to better
reversals. Histology (H&E and toluidine blue) confirmed healing of precancerous
lesions.
PMID- 28690173
TI - Immediate and delayed hyperbaric oxygen therapy as a neuroprotective treatment
for traumatic brain injury in mice.
AB - BACKGROUND: Traumatic brain injury is the most common cause of death or chronic
disability among people under-35-years-old. There is no effective pharmacological
treatment currently existing for TBI. Hyperbaric oxygen therapy (HBOT) is defined
as the inhalation of pure oxygen in a hyperbaric chamber that is pressurized
higher than 1atm. HBOT offers physiological and mechanical effects by inducing a
state of increased pressure and hyperoxia. HBOT has been proposed as an effective
treatment for moderate traumatic brain injury (mTBI), yet the exact therapeutic
window and mechanism that underlies this effect is not completely understood.
METHODS: HBOT was administrated for 4 consecutive days, post a mouse closed head
weight drop moderate TBI (mTBI) in 2 different time lines: immediate treatment -
initiated 3h post-injury and delayed treatment - initiated 7days post-injury.
Behavioral cognitive tests and biochemical changes were assessed. RESULTS: The
results were similar for both the immediate and the delayed treatments. mTBI mice
exhibited impairment in learning abilities, whereas mTBI mice treated with HBO
displayed significant improvement compared with the mTBI group, performing
similar to the sham groups. mTBI mice had a decline in myelin basic protein, an
increase in neuronal loss (NeuN staining), and an increase in the number of
reactive astrocytes (GFAP). The HBO treated mice in both groups did not exhibit
these changes and remained similar to the sham group. CONCLUSIONS: The delayed
HBOT has a potential to serve as a neuroprotective treatment for mTBI with a long
therapeutic window. Further research is needed for fully understanding the
cellular changes.
PMID- 28690174
TI - Clinical outcomes of donation after circulatory death liver transplantation in
primary sclerosing cholangitis.
AB - BACKGROUND & AIM: Primary sclerosing cholangitis (PSC) is a progressive fibro
inflammatory cholangiopathy for which liver transplantation is the only life
extending intervention. These patients may benefit from accepting liver donation
after circulatory death (DCD), however their subsequent outcome is unknown. The
aim of this study was to determine the clinical impact of using DCD liver grafts
in patients specifically undergoing transplantation for PSC. METHODS: Clinical
outcomes were prospectively evaluated in PSC patients undergoing transplantation
from 2006 to 2016 stratified by donor type (DCD, n=35 vs. donation after
brainstem death [DBD], n=108). RESULTS: In liver transplantation for PSC;
operating time, days requiring critical care support, total ventilator days,
incidence of acute kidney injury, need for renal replacement therapy (RRT) or
total days requiring RRT were not significantly different between DCD vs. DBD
recipients. Although the incidence of ischaemic-type biliary lesions was greater
in the DCD group (incidence rate [IR]: 4.4 vs. 0 cases/100-patient-years;
p<0.001) there was no increased risk of post-transplant biliary strictures
overall (hazard ratio [HR]: 1.20, 0.58-2.46; p=0.624), or in sub-analysis
specific to anastomotic strictures or recurrent PSC, between donor types. Graft
loss and mortality rates were not significantly different following
transplantation with DCD vs. DBD livers (IR: 3.6 vs. 3.1 cases/100-patient-years,
p=0.34; and 3.9 vs. 4.7, p=0.6; respectively). DCD liver transplantation in PSC
did not impart a heightened risk of graft loss (HR: 1.69, 0.58-4.95, p=0.341) or
patient mortality (0.75, 0.25-2.21, p=0.598). CONCLUSION: Transplantation with
DCD (vs. DBD) livers in PSC patients does not impact graft loss or patient
survival. In an era of organ shortage, DCD grafts represent a viable therapeutic
option for liver transplantation in PSC patients. Lay summary: This study
examines the impact of liver transplantation in primary sclerosing cholangitis
(PSC) with organs donated after circulatory death (DCD), compared to donation
after brainstem death (DBD). We show that in appropriately selected patients, the
outcomes for DCD transplantation mirror those using DBD livers, with no
significant differences in complication rate, patient survival or transplanted
liver survival. In an era of organ shortage and increasing wait-list times, DCD
livers represent a potential treatment option for transplantation in PSC.
PMID- 28690175
TI - Serum metabolic signatures in patients with overt hepatic encephalopathy.
PMID- 28690176
TI - Evaluation of the current guidelines for resection of hepatocellular carcinoma
using the Appraisal of Guidelines for Research and Evaluation II instrument.
AB - BACKGROUND & AIMS: Numerous guidelines for the management of hepatocellular
carcinoma (HCC) have been developed. The Appraisal of Guidelines for Research &
Evaluation (AGREE II) is the only validated instrument to assess the
methodological quality of guidelines. We aim to appraise the methodological
quality of existing guidelines for the resection of HCC using the AGREE II
instrument. METHODS: Cochrane, Medline, Google Scholar and Embase were searched
using both PRISMA (Preferred Reporting Items for Systematic Reviews and Meta
Analyses) criteria and free text. The assessment of the included clinical
practice guidelines and consensuses were performed using the AGREE II instrument,
version 2013. Guidelines with a score ?80% for the overall appraisal item were
considered as applicable without modifications. RESULTS: Literature searches
identified 22 clinical practice guidelines. Five out of 22 guidelines passed the
70% mark on overall assessment, 11 out of 22 had shortcomings on indications,
contraindications, side effects, key recommendations, technical aspects,
transparency and health economics. Ten of 22 scored below the 50% mark showing
that the guideline had low methodological and overall quality. Only 3/22 clinical
practice guidelines were considered applicable without modifications.
CONCLUSIONS: The methodological quality of guidelines for the surgical management
of HCC is generally poor. Future guideline development should be informed by the
use of the AGREE II instrument. Guidelines based upon high quality evidence could
improve stratification of patients and individualized treatment strategies. Lay
summary: The methodology of clinical practice guidelines for resection for
hepatocellular carcinoma (HCC) evaluated with the Appraisal of Guidelines for
Research & Evaluation (AGREE II) instrument is generally poor. However, there are
some clinical practice guidelines that are based upon higher quality evidence and
can form the framework within which patients with HCC can be selected for
surgical resection. Future guideline development should be informed by the use of
the AGREE II instrument.
PMID- 28690177
TI - Reply to: "Fructose, uric acid and zonal differences in NASH".
PMID- 28690178
TI - Fructose, uric acid, and zonal differences in NASH.
PMID- 28690179
TI - Polydopamine-immobilized polypropylene microfuge tube as a pH-responsive platform
for capture/release of DNA from foodborne pathogens.
AB - A rapid, convenient and efficient DNA extraction method with no need for toxic
agents and centrifugation was reported. A polypropylene microfuge (MF) tube was
used as the substrate to immobilize polydopamine (PDA). The prepared PDA-coated
MF (PDA@MF) tube was used as a pH-responsive platform for rapid extraction of DNA
based on pH-induced charge switch of amino and phenolic hydroxyl groups in PDA
coating. The extraction procedure is simple and can be finished in 25 min. The
PDA@MF tube was applied for extraction of genomic DNA from foodborne pathogens in
milk. The extracted DNA was directly used as template for PCR amplification.
PMID- 28690180
TI - Development of an immunosensor for quantifying zebrafish vitellogenin based on
the Octet system.
AB - Vitellogenin (Vtg) is a sensitive biomarker for environmental estrogens. In this
study, an immunosensor for quantifying zebrafish Vtg was developed using the
Octet system. First, Protein A sensors were immobilized with purified anti
lipovitellin (Lv) antibody that demonstrated specificity to Vtg. Then, antibody
coated biosensors were immersed into zebrafish Lv standards and diluted samples.
The Octet system measured and recorded kinetic parameters between antigens and
captured antibody within 5 min. Sample Vtg concentrations were automatically
calculated by interpolating relative binding rates observed with each sample and
the immobilized anti-Lv antibody into the developed standard curve. The sensor
arrays exhibited a wide linear range from 78 to 5000 ng/mL, and the inter-assay
coefficient of variation was 0.66-1.97%. Furthermore, the performance of the
immunosensor in detecting Vtg was evaluated by quantifying Vtg induction in
juvenile zebrafish exposed to 17beta-estradiol (E2). Compared with conventional
immunoassay techniques, the Vtg immunosensor developed based on the Octet system
was much simpler and less time-consuming, allowing rapid Vtg quantification
within 15 min. Moreover, Protein A sensors could be reused many times to ensure
that the assays have high reproducibility. Therefore, we suggest that
immunosensors based on the Octet system are an easily operated detection method
for ecotoxicological research.
PMID- 28690181
TI - Hydrogen peroxide agarose gels for electrophoretic analysis of RNA.
AB - Efficient electrophoretic separation of isolated total RNA utilizes chemicals and
agents to aid in nuclease free environment. However cost, extensive pre-run
processing protocols as well as toxic byproducts limit the usage of such
protocols. Moreover, these treatments affect the overall electrophoretic results
by altering the conductivity of the running buffer and weaken the gel strength.
We here provide a protocol for RNA visualization that obviates these shortcomings
by preparation of agarose gel with hydrogen peroxide using the regular TAE
buffer. The simple, inexpensive protocol exhibits superior results in a
horizontal agarose gel electrophoresis.
PMID- 28690182
TI - Functional characterization of a soluble NADPH-cytochrome P450 reductase from
Fusarium graminearum.
AB - Fusarium head blight is a devastating disease in wheat caused by some fungal
pathogens of the Fusarium genus mainly F. graminearum, due to accumulation of
toxic trichothecenes. Most of the trichothecene biosynthetic pathway has been
mapped, although some proteins of the pathway remain uncharacterized, including
an NADPH-cytochrome P450 reductase. We subcloned a F. graminearum cytochrome P450
reductase that might be involved in the trichothecene biosynthesis. It was
expressed heterologously in E. coli as N-terminal truncated form with an
octahistidine tag for purification. The construct yielded a soluble apoprotein
and its incubation with flavins yielded the corresponding monomeric holoprotein.
It was characterized for activity in the pH range 5.5-9.5, using thiazolyl blue
tetrazolium bromide (MTT) or cytochrome c as substrates. Binding of the small
molecule MTT was weaker than for cytochrome c, however, the rate of MTT reduction
was faster. Contrary to other studies of cytochrome reductase proteins, MTT
reduction proceeded in a cooperative manner in our studies. Optimum kinetic
activity was found at pH 7.5-8.5 for bothMTT and cytochrome c. This is the first
paper presenting characterization of a cytochrome P450 reductase from F.
graminearum which most likely is involved in mycotoxin biosynthesis or some
primary metabolic pathway such as sterol biosynthesis in F. graminearum.
PMID- 28690183
TI - Perinatal protein deprivation facilitates morphine cross-sensitization to cocaine
and enhances DeltaFosB expression in adult rats.
AB - Previous studies have indicated that neural changes induced by early nutritional
insult cause an altered response to pharmacological treatments, including
addictive drugs. This study evaluates the influence of perinatal protein
malnutrition in developing cross-sensitization to cocaine-induced rewarding
effects in animals pre-exposed to morphine. Different groups of well-nourished (C
rats) and protein-deprived animals (D-rats) were treated twice a day for three
days with increasing doses of morphine or with saline. After 3days, the incentive
motivational effects of cocaine were assessed in a Conditioned Place Preference
paradigm in both groups. In saline pre-treated animals, dose-response curves to
cocaine revealed a conditioning effect in D-rats at doses of 5, 7.5 and 10mg/kg,
while this effect was observed in C-rats only with 10 and 15mg/kg. Furthermore,
when animals of both groups were pre-treated with escalating doses of morphine,
cross-sensitization to the conditioning effect of cocaine was elicited only in D
rats with low doses of cocaine (5 and 7.5mg/kg). In contrast, under the same
experimental conditions, C-rats show no cross-sensitization. To correlate this
differential rewarding response with a molecular substrate linked to the
behavioral changes observed after repeated drug exposure, DeltaFosB expression
was assessed in different brain regions. D-rats showed a significant increase in
this transcription factor in the nucleus accumbens, amygdala and medial
prefrontal cortex. These results demonstrated that perinatal protein deprivation
facilitates rewarding effects and the development of cross-sensitization to
cocaine, which correlates with an upregulation of DeltaFosB in brain areas
related to the reward circuitry.
PMID- 28690184
TI - Evaluating aged mice in three touchscreen tests that differ in visual demands:
Impaired cognitive function and impaired visual abilities.
AB - Normal aging is often accompanied by reductions in cognitive abilities as well as
impairments in visual acuity in men and mice. In preclinical models of human
cognition this concomitance can make it difficult to assess the relative
contributions of declined vision and cognitive ability on behavioral measures of
cognition. To assess the influence of age on cognition and the impact of visual
decline on the performance of touchscreen-based behavioral paradigms in mice,
aged (11, 12, 16, 17, 19 and 21 months old) male C57BL/6J mice were compared to
young (3 or 4 months old) male C57BL/6J mice using three tests of cognition as
well as an assessment of visual acuity. Performance of a Visual Discrimination,
Spatial Reversal, and an Automated Search Task were all affected by age. However,
there was no relationship between reduced visual acuity and the observed
performance impairments. Moreover, the visual acuity of animals with profound
cognitive impairments overlapped with those showing normal cognitive ability.
Despite the potential confound of impaired visual ability, it appears that the
touchscreen approach might be particularly effective in studying age-related
cognitive decline. This approach will increase the utility of aged mice as a
model of decreased cognitive flexibility and may be particularly important for
the study of age-related disorders such as Alzheimer's disease.
PMID- 28690185
TI - Selection of similar single domain antibodies from two immune VHH libraries
obtained from two alpacas by using different selection methods.
AB - The two most used methods to select camelid single-domain antibody-fragments
(VHHs) are: displaying their repertoires on the surface of filamentous
bacteriophages (phage display) or linking them to ribosomes (ribosome display).
In this study, we compared specific VHHs isolated from two different immune
libraries coming from two different alpacas by using these two selection methods.
Three anti-GFAP (glial fibrillary acidic protein) VHHs were derived from an
immune library obtained by ribosome display after immunization of one alpaca with
purified GFAP, a protein expressed by astroglial cells. In parallel, three other
anti-GFAP VHHs were derived from an immune library by phage display after
immunization of another alpaca with a human brain tissue extract containing GFAP.
All the VHHs were closely related and one VHH was found to be strictly identical
in both studies. This highlights the selection pressure exerted by the camelid
immune system to shape the paratope of an antibody against a defined antigen.
PMID- 28690186
TI - CCL2 promoter hypomethylation is associated with gout risk in Chinese Han male
population.
AB - OBJECTIVES: C-C motif chemokine ligand 2 (CCL2) encodes a chemokine which
amplifies and maintains inflammation through chemokine-cytokine networks. Gout is
a type of painful inflammation arthritis in response to the deposition of
monosodium urate (MSU) crystals in joints. The purpose of this study was to
figure out the role of CCL2 promoter methylation in gout. METHODS: A quantitative
methylation-specific polymerase chain reaction (qMSP) was used to measure CCL2
promoter methylation in 93 gout patients and 101 healthy controls, respectively.
All participants were Chinese Han males. The percent of methylated reference
(PMR) was used to evaluate methylation level of each sample. RESULTS: In the
current study, we have found that CCL2 promoter methylation was significantly
lower in gout than in healthy controls (24.95% versus 42.68%, P<0.001). CCL2
promoter hypermethylation was considered as a risk factor of gout [OR (95%
CI)=3.59E-04 (5.67E-06, 0.023), P=1.79E-04]. Receiver operating characteristic
(ROC) curve analysis showed there was a significant diagnostic value of CCL2
hypomethylation for gout (AUC=0.763, 95% CI=0.695-0.830, sensitivity=0.644,
specificity=0.849). CONCLUSIONS: CCL2 promoter hypomethylation in peripheral
blood could be a potential biomarker for the diagnosis of gout in Chinese Han
males.
PMID- 28690188
TI - Aging across the tree of life: The importance of a comparative perspective for
the use of animal models in aging.
AB - Use of model organisms in aging research is problematic because our ability to
extrapolate across the tree of life is not clear. On one hand, there are
conserved pathways that regulate lifespan in organisms including yeast,
nematodes, fruit flies, and mice. On the other, many intermediate taxa across the
tree of life appear not to age at all, and there is substantial variation in
aging mechanisms and patterns, sometimes even between closely related species.
There are good evolutionary and mechanistic reasons to expect this complexity,
but it means that model organisms must be used with caution and that results must
always be interpreted through a broader comparative framework. Additionally, it
is essential to include research on non-traditional and unusual species, and to
integrate mechanistic and demographic research. There will be no simple answers
regarding the biology of aging, and research approaches should reflect this. This
article is part of a Special Issue entitled: Animal models of aging - edited by
Houtkooper Riekelt.
PMID- 28690187
TI - Evaluating of OCT-4 and NANOG was differentially regulated by a new derivative
indole in leukemia cell line.
AB - BACKGROUND: The potential exists to improve treatment through characterization of
tumor stem cells and identification of therapeutic targets Using OCT-4 and NANOG
genes. Here we have synthesized and investigated the potential of; New Indole-3
carbaldehyde derivative (NI-3-CD) in inhibiting the expression of self-renewal
regulatory factors and cancer stem cell gene in a leukemia cell line NB4.
METHODOLOGY: The NB4 cells were cultured in RPMI1640 medium contained NI-3-CD and
I3F (15.12-1000MUg/mL) for 24, 48 and 72h. Inhibition of cell proliferation was
assessed by trypan blue staining technique and MTT assay. The percentage of
apoptotic cells was determined by flow cytometry analysis using Annexin V/PI
apoptosis detection kit. The fold changes of NANOG/OCT4 expression against beta
actin were determined by real-time-PCR technique. Western blotting analysis was
also applied for evaluating the expression of NANOG/OCT4 at protein level. Data
were analyzed by student t and repeated measure tests. Differences were
considered significant if (P<0.01). RESULTS: There was a significant difference
in cell viability, when various concentrations of NI-3- were used for 24, 48 and
72h in comparison to I3C regarding the cellular viability. Furthermore, the NI-3
CD, had markedly elevated anticancer activity than I3C (IC50 values for novel I3C
in 24, 48 and 72h were 225.77, 123.13 and 63.72M respectively while for I3C were
728.05, 407.82 and 277.92M respectively). Flow cytometry results exhibited an
obviously significant augmentation in apoptotic NB4 cells. Real Time- PCR
analysis indicated that the expression of NANOG/OCT4 was down regulated in
compare to untreated control cells and I3C treated cells (P<0.05). In concert
with RT-PCR, western blot analysis showed that the OCT4 expression in NI-3-CD
treated cells was also significantly decreased in compare to both untreated
control cells and I3C treated cellular populations. CONCLUSION: Our results imply
that NI-3-CD treatment decreases the sphere-forming ability of NB4 cells. In
summary, this study provides valuable information on the presence of stem-cell
genes expression in NB4 cells.
PMID- 28690189
TI - Efavirenz: What is known about the cellular mechanisms responsible for its
adverse effects.
AB - The HIV infection remains an important health problem worldwide. However, due to
the efficacy of combined antiretroviral therapy (cART), it has ceased to be a
mortal condition, becoming a chronic disease instead. Efavirenz, the most
prescribed non-nucleoside analogue reverse transcriptase inhibitor (NNRTI), has
been a key component of cART since its commercialization in 1998. Though still a
drug of choice in many countries, its primacy has been challenged by the arrival
of newer antiretroviral agents with better toxicity profiles and treatment
adherence. The major side effects related to EFV have been widely described in
clinical studies, however the mechanisms that participate in their pathogenesis
remain largely ununderstood. This review provides an insight into the cellular
and molecular mechanisms responsible for the development of the most significant
undesired effects induced by efavirenz, both short- and long-term, revealed by in
vitro and in vivo experimental pharmacological research. Growing evidence
implicates the drug in energy metabolism, mitochondrial function, and other
cellular processes involved in stress responses including oxidative stress,
inflammation and autophagy.
PMID- 28690190
TI - Immunomodulatory potential of hesperetin and chrysin through the cellular and
humoral response.
AB - Flavonoids are polyphenols frequently consumed in the diet they have been
suggested to exert a number of beneficial actions on human health, including anti
inflammatory activity. This study investigated the immunomodulatory effects of
two flavonoids, Chrysin and Hesperetin. The effects of flavonoids on B and T cell
proliferation were assessed on splenocytes stimulated or not with mitogens.
However, their effects on cytotoxic T lymphocyte (CTL) and natural killer (NK)
activities were assessed in splenocytes co-incubated with target cells. We report
for the first time that both tested flavonoids enhance lymphocyte proliferation
at 3.12MUM. Chrysin significantly inhibited lipopolysaccharide (LPS) and lectin
stimulated splenocyte proliferation. Whereas, hesperetin enhanced LPS and lectin
stimulated splenocyte proliferation. In addition, both flavonoids significantly
enhance NK cell and CTL activities. Furthermore, our study demonstrated that
depending on the concentrations, flavonoid molecules affect macrophage functions
by modulating their lysosomal activity and nitric oxide (NO) release, suggesting
a potential anti-inflammatory effect. We conclude that flavonoids such as chrysin
and hesperetin may be potentially useful for modulating immune cell functions in
physiological and pathological conditions and thus a good candidate as food
addition component.
PMID- 28690191
TI - Methyl (E)-(3-(3,4-dihydroxyphenyl)acryloyl)tryptophanate can suppress MCP-1
expression by inhibiting p38 MAP kinase and NF-kappaB in LPS-stimulated
differentiated THP-1 cells.
AB - Methyl (E)-(3-(3,4-dihydroxyphenyl)acryloyl)tryptophanate (MHAT) is an O-methyl
ester of javamide-II showing strong anti-inflammatory activity. Therefore, in
this study, MHAT was chemically synthesized, and its effects on p38 MAP kinase,
NF-kappaB, and monocyte chemotactic factor-1 (MCP-1) expression were investigated
in LPS-stimulated differentiated THP-1 cells. MHAT inhibited p38 MAP kinase with
an IC50 of 12MUM, and the inhibition was supported by an in silico model showing
that its binding to p38 MAP kinase was stronger than that of SB203580. At the
concentration of 20MUM, the p38 inhibition reduced ATF-2 phosphorylation by 55%
(P < 0.05). Additionally, MHAT inhibited NF-kappaB (p65) phosphorylation by 30%
(P < 0.05) at the same concentration, suggesting that MHAT was able to reduce NF
kappaB transcriptional activity. This supposition was confirmed by the NF-kappaB
reporter assay, demonstrating that MHAT (20MUM) could suppress NF-kappaB
transcriptional activity by 29% (P < 0.05) in the NF-kappaB reporter (Luc)-HEK293
cell line. As expected, the treatment with MHAT (5-40MUM) significantly inhibited
MCP-1 mRNA expression by 9-73% (P < 0.05) and the production of MCP-1 protein by
10-70% (P < 0.05) in the THP-1 cells. Furthermore, MHAT was found to inhibit
RANTES expression as well in the same THP-1 cells, supporting its purported
inhibition of p38 MAP kinase and NF-kappaB. All these data suggest that MHAT is a
potent compound that can inhibit MCP-1 production by suppressing p38 kinase/ATF-2
phosphorylation and NF-kappaB in the differentiated THP-1 cells.
PMID- 28690192
TI - Suppression of osteogenic differentiation in mesenchymal stem cells from patients
with ossification of the posterior longitudinal ligament by a histamine-2
receptor antagonist.
AB - Mesenchymal stem cells (MSCs) in ossification of the posterior longitudinal
ligament (OPLL) patients have a high propensity toward osteogenesis. Histamine
receptor H2 (H2R) antagonists (H2 blockers) like famotidine decrease ossification
in patients, by an unclear mechanism. To confirm that MSCs express H2R and to
clarify how H2 blockers suppress osteogenic differentiation, we used spinal
ligament MSCs from patients with OPLL or with cervical spondylotic myelopathy
(CSM) (control). The MSCs were treated with 10, 30, or 100nM famotidine for 7 or
21 days. Flow cytometry revealed that cells from both groups expressed MSC
surface markers CD44, CD90, and CD105 (> 97.5%) but not CD34 or CD45 (< 2.5%).
Immunoblotting showed that the MSCs from both groups expressed H2R, but those
from OPLL patients expressed it at higher levels. Real-time qPCR indicated the
H2R expression was significantly suppressed by 30nM famotidine for 7 days or by
30 or 100nM for 21 days. However, histidine decarboxylase, a key enzyme in
histamine production, did not change significantly after famotidine addition.
Famotidine treatment at 100nM for 21 days significantly suppressed mRNA
expression of the osteogenic markers osteocalcin (OCN), bone morphogenetic
protein 2 (BMP2), and runt-related transcription factor 2 (RUNX2) only in OPLL
derived MSCs. Immunoblots showed that famotidine suppressed BMP2 and OCN in the
OPLL group and H2R and RUNX2 in both groups. These results suggest famotidine
inhibits osteogenic differentiation in OPLL-derived MSCs by acting as an H2R
antagonist, but also by decreasing H2R expression, and support the clinical use
of famotidine to treat OPLL.
PMID- 28690193
TI - Synergistic inhibition of Abeta production by combinations of gamma-secretase
modulators.
AB - Alzheimer's disease is associated with the accumulation of amyloid-beta (Abeta)
in the brain. In particular, the 42-amino acid form, Abeta1-42, is thought to
play a key role in the disease. It is therefore of interest that diverse
compounds, known as gamma-secretase modulators (GSM), can selectively decrease
Abeta1-42 production without inhibiting the production of other forms of Abeta.
Here we describe the novel discovery of synergistic inhibition of Abeta by
certain combinations of GSMs. Cell cultures were treated with pairwise
combinations of GSMs to determine how Abeta peptide production was affected.
Analysis of isobolograms and calculation of the combination index showed that BMS
869780 and GSM-2 were highly synergistic. Additional combinations of GSMs
revealed that inhibition of Abeta occurred only when one GSM was of the "acid
GSM" structural class and the other was of the "non-acid GSM" class. A total of
15 representative acid/non-acid GSM combinations were shown to inhibit Abeta
production, whereas 10 pairwise combinations containing two acid GSMs or
containing two non-acid GSMs did not inhibit Abeta. We also discovered that
lasalocid, a natural product, is a potent GSM. Lasalocid is unique in that it did
not synergize with other GSMs. Synergism did not translate in vivo perhaps
because of biochemical differences between the cell culture model and brain.
These findings reinforce the pharmacological differences between different
structural classes of GSMs, and may help to exploit the potential of gamma
secretase as a drug target.
PMID- 28690195
TI - Low molar excess of 4-oxo-2-nonenal and 4-hydroxy-2-nonenal promote
oligomerization of alpha-synuclein through different pathways.
AB - Aggregated alpha-synuclein is the main component of Lewy bodies, intraneuronal
inclusions found in brains with Parkinson's disease and dementia with Lewy
bodies. A body of evidence implicates oxidative stress in the pathogenesis of
these diseases. For example, a large excess (30:1, aldehyde:protein) of the lipid
peroxidation end products 4-oxo-2-nonenal (ONE) or 4-hydroxy-2-nonenal (HNE) can
induce alpha-synuclein oligomer formation. The objective of the study was to
investigate the effect of these reactive aldehydes on alpha-synuclein at a lower
molar excess (3:1) at both physiological (7.4) and acidic (5.4) pH. As observed
by size-exclusion chromatography, ONE rapidly induced the formation of alpha
synuclein oligomers at both pH values, but the effect was less pronounced under
the acidic condition. In contrast, only a small proportion of alpha-synuclein
oligomers were formed with low excess HNE-treatment at physiological pH and no
oligomers at all under the acidic condition. With prolonged incubation times (up
to 96h), more alpha-synuclein was oligomerized at physiological pH for both ONE
and HNE. As determined by Western blot, ONE-oligomers were more SDS-stable and to
a higher-degree cross-linked as compared to the HNE-induced oligomers. However,
as shown by their greater sensitivity to proteinase K treatment, ONE-oligomers,
exhibited a less compact structure than HNE-oligomers. As indicated by mass
spectrometry, ONE modified most Lys residues, whereas HNE primarily modified the
His50 residue and fewer Lys residues, albeit to a higher degree than ONE. Taken
together, our data show that the aldehydes ONE and HNE can modify alpha-synuclein
and induce oligomerization, even at low molar excess, but to a higher degree at
physiological pH and seemingly through different pathways.
PMID- 28690194
TI - Examining a role for PKG Ialpha oxidation in the pathogenesis of cardiovascular
dysfunction during diet-induced obesity.
AB - BACKGROUND: Protein kinase G (PKG) Ialpha is the end-effector kinase that
mediates nitric oxide (NO)-dependent and oxidant-dependent vasorelaxation to
maintain blood pressure during health. A hallmark of cardiovascular disease is
attenuated NO production, which in part is caused by NO Synthase (NOS)
uncoupling, which in turn increases oxidative stress because of superoxide
generation. NOS uncoupling promotes PKG Ialpha oxidation to the interprotein
disulfide state, likely mediated by superoxide-derived hydrogen peroxide, and
because the NO-cyclic guanosine monophosphate (cGMP) pathway otherwise negatively
regulates oxidation of the kinase to its active disulfide dimeric state. Diet
induced obesity is associated with NOS uncoupling, which may in part contribute
to the associated cardiovascular dysfunction due to exacerbated PKG Ialpha
disulfide oxidation to the disulfide state. This is a rational hypothesis because
PKG Ialpha oxidation is known to significantly contribute to heart failure that
arises from chronic myocardial oxidative stress. METHODS AND RESULTS: Bovine
arterial endothelial cells (BAECs) or smooth muscle cells (SMCs) were exposed to
drugs that uncouple NOS. These included 1,3-bis(2-chloroethyl)-1-nitrosourea
(BCNU) which promotes its S-glutathiolation, 4-diamino-6-hydroxy-pyrimidine
(DAHP) which inhibits guanosine-5'-triphosphate-cyclohydrolase 2 to prevent BH4
synthesis or methotrexate (MTX) which inhibits the regeneration of BH4 from BH2
by dihydrofolate reductase. While all the drugs mentioned above induced robust
PKG Ialpha disulfide dimerization in cells, exposure of BAECs to NOS inhibitor L
NMMA did not. Increased PKG Ialpha disulfide formation occurred in hearts and
aortae from mice treated in vivo with DAHP (10mM in a drinking water for 3
weeks). Redox-dead C42S PKG Ialpha knock-in (KI) mice developed less pronounced
cardiac posterior wall hypertrophy and did not develop cardiac dysfunction,
assessed by echocardiography, compared to the wild-type (WT) mice after chronic
DAHP treatment. WT or KI mice were then subjected to a diet-induced obesity
protocol by feeding them with a high fat Western-type diet (RM 60% AFE) for 27
weeks, which increased body mass, adiposity, plasma leptin, resistin and glucagon
levels comparably in each genotype. Obesity-induced hypertension, assessed by
radiotelemetry, was mild and transient in the WT, while the basally hypertensive
KI mice were resistant to further increases in blood pressure following high fat
feeding. Although the obesogenic diet caused mild cardiac dysfunction in the WT
but not the KI mice, gross changes in myocardial structure monitored by
echocardiography were not apparent in either genotype. The level of cyclic
guanosine monophosphate (cGMP) was decreased in the aortae of WT and KI mice
following high fat feeding. PKG Ialpha oxidation was not evident in the hearts of
WT mice fed a high fat diet. CONCLUSIONS: Despite robust evidence for PKG Ialpha
oxidation during NOS uncoupling in cell models, it is unlikely that PKG Ialpha
oxidation occurs to a significant extent in vivo during diet-induced obesity and
so is unlikely to mediate the associated cardiovascular dysfunction.
PMID- 28690196
TI - Linking arsenite- and cadmium-generated oxidative stress to microsatellite
instability in vitro and in vivo.
AB - Mismatch repair (MMR) corrects replicative errors and minimizes DNA damage that
occurs frequently in microsatellites. MMR deficiency is manifested as
microsatellite instability (MSI), which contributes to hypermutability and cancer
pathogenesis. Genomic instability, including MSI and chromosomal instability,
appears to be responsible for the carcinogenesis of arsenic and cadmium, common
contaminants in our environment. However, few studies have addressed arsenic- or
cadmium-induced MSI, especially its potential link with arsenic- or cadmium
generated oxidative stress, due to the lack of quantifiable MSI assays and cost
effective animal models. Here, using a dual-fluorescent reporter, we demonstrate
that sub-lethal doses of cadmium or arsenite, but not arsenate, increased the MSI
frequency in human colorectal cancer cells. Arsenite- and cadmium-induced MSI
occurred concomitantly with increased levels of reactive species and oxidative
DNA damage, and with decreased levels of MMR proteins. However, N-acetyl-l
cysteine (NAC) suppressed arsenite- and cadmium-induced MSI and oxidative stress
while restoring the levels of MMR proteins in the cells. Similarly, MSI was
induced separately by arsenite and cadmium, and suppressed by NAC, in zebrafish
in a fluorescinated PCR-based assay with newly-developed microsatellite markers
and inter-segmental comparisons. Of five selected antioxidants examined,
differential effects were exerted on the MSI induction and cytotoxicity of both
arsenite and cadmium. Compared to MMR-proficient cells, MMR-deficient cells were
more resistant to arsenic-mediated and cadmium-mediated cytotoxicity. Our
findings demonstrate a novel linkage between arsenite-generated and cadmium
generated oxidative stress and MSI induction. Our findings also caution that
antioxidants must be individually validated before being used for preventing
arsenite- and cadmium-induced MSI that is associated with cancer development.
PMID- 28690197
TI - High-fat diet induces skeletal muscle oxidative stress in a fiber type-dependent
manner in rats.
AB - This study investigated the effects of high-fat (HF) diet on parameters of
oxidative stress among muscles with distinct fiber type composition and oxidative
capacities. To accomplish that, male Wistar rats were fed either a low-fat
standard chow (SC) or a HF diet for 8 weeks. Soleus, extensor digitorum longus
(EDL), and epitrochlearis muscles were collected and mitochondrial H2O2 (mtH2O2)
emission, palmitate oxidation, and gene expression and antioxidant system were
measured. Chronic HF feeding enhanced fat oxidation in oxidative and glycolytic
muscles. It also caused a significant reduction in mtH2O2 emission in the EDL
muscle, although a tendency towards a reduction was also found in the soleus and
epitrochlearis muscles. In the epitrochlearis, HF diet increased mRNA expression
of the NADPH oxidase complex; however, this muscle also showed an increase in the
expression of antioxidant proteins, suggesting a higher capacity to generate and
buffer ROS. The soleus muscle, despite being highly oxidative, elicited H2O2
emission rates equivalent to only 20% and 35% of the values obtained for EDL and
epitrochlearis muscles, respectively. Furthermore, the Epi muscle with the lowest
oxidative capacity was the second highest in H2O2 emission. In conclusion, it
appears that intrinsic differences related to the distribution of type I and type
II fibers, rather than oxidative capacity, drove the activity of the anti- and
pro-oxidant systems and determine ROS production in different skeletal muscles.
This also suggests that the impact of potentially deleterious effects of ROS
production on skeletal muscle metabolism/function under lipotoxic conditions is
fiber type-specific.
PMID- 28690198
TI - Punicalagin, a PTP1B inhibitor, induces M2c phenotype polarization via up
regulation of HO-1 in murine macrophages.
AB - Current data have shown that punicalagin (PUN), an ellagitannin isolated from
pomegranate, possesses anti-inflammatory and anti-oxidant properties; however,
its direct targets have not yet been reported. This is the first report that
PTP1B serves as a direct target of PUN, with IC50 value of 1.04MUM. Results from
NPOI further showed that the Kon and Koff of PUN-PTP1B complex were 3.38e2M-1s-1
and 4.13e-3s-1, respectively. The active site Arg24 of PTP1B was identified as a
key binding site of PUN by computation simulation and point mutation. Moreover,
inhibition of PTP1B by PUN promoted an M2c-like macrophage polarization and
enhanced anti-inflammatory cytokines expression, including IL-10 and M-CSF. Based
on gene expression profile, we elucidated that PUN treatment significantly up
regulated 275 genes and down-regulated 1059 genes. M1-like macrophage marker
genes, such as Tlr4, Irf1/2, Hmgb1, and Stat1 were down-regulated, while M2
marker genes, including Tmem171, Gpr35, Csf1, Il1rn, Cebpb, Fos, Vegfalpha,
Slc11a1, and Bhlhe40 were up-regulated in PUN-treated macrophages. Hmox-1, a gene
encoding HO-1 protein, was preferentially expressed with 16-fold change.
Inhibition of HO-1 obviously restored PUN-induced M2 polarization and IL-10
secretion. In addition, phosphorylation of both Akt and STAT3 contributed to PUN
induced HO-1 expression. This study provided new insights into the mechanisms of
PUN-mediated anti-inflammatory and anti-oxidant activities and provided new
therapeutic strategies for inflammatory diseases.
PMID- 28690199
TI - High-concentration protein formulations: How high is high?
AB - High-concentration protein formulation (HCPF) is a term that is used to describe
protein formulations, mostly monoclonal antibody (mAb) drugs, at high protein
concentration. The concentration is rarely defined, with typical ranges varying
between 50 and 150mg/ml for mAbs. The term HCPF is meant to include and express
specific solution properties of formulations that are prone to appear at high
protein concentrations such as high viscosity, high opalescence, phase
separation, gel formation or the increased propensity for protein particle
formation. Thus the term HCPF can be understood as a descriptor of protein
formulations, usually at high protein (monoclonal antibody) concentrations, which
have specific solution, stability and colloidal properties that differ from
formulations at low protein concentration (e.g. at 10mg/ml). The current paper
highlights in brief the development challenges that might occur for high
concentration protein/monoclonal antibody formulations. In particular, the
maximum concentration regimes achievable in HCPF remained unclear. Based on
geometrical considerations involving packing of monoclonal antibodies in a
lattice we map out a maximum concentration range that might be theoretically
achievable. Different geometrical assumptions and packing models are compared and
their relevance is critically discussed, in particular concerning the influence
of the physicochemical properties of the monoclonal antibodies on their
solubility, which is neglected in the simple geometrical model. According to our
estimates, monoclonal antibody concentration above 500mg/ml will be very
challenging to achieve. Our results have implications for setting up realistic
drug product development strategies and for preparing convincing drug target
product profiles for development.
PMID- 28690200
TI - Functional electrospun fibers for the treatment of human skin wounds.
AB - Wounds are trauma induced defects of the human skin involving a multitude of
endogenous biochemical events and cellular reactions of the immune system. The
healing process is extremely complex and affected by the patient's physiological
conditions, potential implications like infectious pathogens and inflammation as
well as external factors. Due to increasing incidence of chronic wounds and
proceeding resistance of infection pathogens, there is a strong need for
effective therapeutic wound care. In this context, electrospun fibers with
diameters in the nano- to micrometer range gain increasing interest. While
resembling the structure of the native human extracellular matrix, such fiber
mats provide physical and mechanical protection (including protection against
bacterial invasion). At the same time, the fibers allow for gas exchange and
prevent occlusion of the wound bed, thus facilitating wound healing. In addition,
drugs can be incorporated within such fiber mats and their release can be
adjusted by the material and dimensions of the individual fibers. The review
gives a comprehensive overview about the current state of electrospun fibers for
therapeutic application on skin wounds. Different materials as well as
fabrication techniques are introduced including approaches for incorporation of
drugs into or drug attachment onto the fiber surface. Against the background of
wound pathophysiology and established therapy approaches, the therapeutic
potential of electrospun fiber systems is discussed. A specific focus is set on
interactions of fibers with skin cells/tissues as well as wound pathogens and
strategies to modify and control them as key aspects for developing effective
wound therapeutics. Further, advantages and limitations of controlled drug
delivery from fiber mats to skin wounds are discussed and a future perspective is
provided.
PMID- 28690201
TI - Neurotensin receptor 1 facilitates intracellular and transepithelial delivery of
macromolecules.
AB - G protein-coupled receptors are expressed on the surface of eukaryotic cells and
internalise in response to ligand binding. The actions of the hormone and
neurotransmitter neurotensin (NT) are predominantly mediated by specific
interactions with one such receptor, neurotensin receptor 1 (NTS1), which is
upregulated in a variety of cancers, including pancreatic and breast tumours.
NTS1 could therefore serve as a target for selective delivery of therapeutics.
This study characterised the expression of NTS1 in HEK293 cells, as well as both
polarised and non-polarised intestinal epithelial Caco-2 cells. NT-conjugated
fluorophores were internalised in NTS1-expressing HEK293 and Caco-2 cells in a
receptor-mediated fashion. Confocal microscopy revealed fluorophore localisation
in the perinuclear region. Cell uptake and transport across the Caco-2 intestinal
model of two NT-conjugated fluorophores (GFP and fluorescein) were compared to
evaluate the effect of cargo size on cellular uptake. This work demonstrates that
NT ligand conjugation is able to deliver relatively large macromolecular cargoes
selectively into cells overexpressing NTS1 and the system is able to effectively
translocate macromolecules across an intestinal epithelial model. NTS1 therefore
shows potential as a drug delivery target not only for targeted but also non
invasive (oral) delivery of biotherapeutics for cancer.
PMID- 28690202
TI - The impact of methylphenidate and its enantiomers on dopamine synthesis and
metabolism in vitro.
AB - Methylphenidate (MPH), a psychostimulant, is an effective first-line treatment
for the symptoms associated with Attention-Deficit/Hyperactivity Disorder (ADHD).
Although most MPH formulations are composed of the racemic 1:1 mixture of the two
enantiomers (d- and l-threo), converging lines of evidence indicate that d-threo
MPH seems to be superior to the l-isomer. We aimed to investigate whether MPH
racemic mixture or pure enantiomers influence the enzyme activity of tyrosine
hydroxylase (TH), monoamine oxidase B (MAO-B), catechol-O-methyltransferase
(COMT), and aldehyde dehydrogenase (ALDH) in vitro in homogenates of rat PC12
cells incubated with racemic, d- and l-threo MPH (1nM up to 100MUM), or a vehicle
for control. We could observe dose dependent enhancement of TH activity with d
threo MPH, probably due to its higher affinity to the enzyme, which we could
confirm for d-threo versus l-threo MPH via docking and molecular dynamic
simulations analysis. MAO-B enzyme activity was found to be enhanced when
incubated with both d- and l-isomers but not with the racemic mixture. This
conflicting result was hypothesized to be due to possible aggregation of the two
enantiomers or other molecular conformations. Such a possible interaction was
observed indirectly, when TH was incubated with constant d-threo MPH while
increasing l-isomer (increasing total MPH concentrations). Hence, TH activity was
slightly decreased with increased l-isomer. In conclusion, the current in vitro
investigation points to the stereoselectivity of the investigated enzymes and
pharmacological effects of MPH enantiomers.
PMID- 28690204
TI - Depressive, anxiety and hypomanic symptoms in schizophrenia may be driven by
tryptophan catabolite (TRYCAT) patterning of IgA and IgM responses directed to
TRYCATs.
AB - The aim of this study was to delineate the associations between the tryptophan
catabolite (TRYCAT) pathway and affective symptoms in schizophrenia. Towards this
end we measured immunoglobulin (Ig)A and IgM responses to relatively noxious
TRYCATs, namely quinolinic (QA), xanthurenic (XA), picolinic (PA) acid and 3-OH
kynurenine (3HK), and generally protective TRYCATs, namely anthranilic (AA) and
kynurenic (KA) acid in 80 patients with schizophrenia and 40 healthy controls.
The Hamilton Rating Scale for Depression (HDRS) and anxiety (HAMA), Young Mania
Rating Scale (YMRS) as well as the Positive and Negative Symptoms Scale of
Schizophrenia (PANSS) were measured. Depression, anxiety and hypomanic as well as
negative and positive symptoms were associated with increased IgA responses to
PA. Increased IgA responses to XA were associated with anxiety, hypomanic and
negative symptoms. Moreover, depressive, anxiety, hypomanic and negative symptoms
were characterized by increased IgA responses to the noxious
(XA+3HK+QA+PA)/protective (AA+KA) TRYCAT ratio. All symptom dimensions were
associated with increased IgM responses to QA, while depressive, anxiety,
positive and negative symptoms were accompanied by lowered IgM responses to 3HK.
Hypomanic symptoms were additionally accompanied by lowered IgM responses to AA,
and negative symptoms by increased IgM responses to KA. In conclusion, both
shared and distinct alterations in the activity of the TRYCAT pathway, as well as
its regulatory factors and consequences, may underpin affective and classical
psychotic symptoms of schizophrenia. Increased mucosa-generated production of
noxious TRYCATs, especially PA, and specific changes in IgM-mediated regulatory
activities may be associated with the different symptom dimensions of
schizophrenia.
PMID- 28690205
TI - Bronchoalveolar Lavage Microvesicles Protect Burn-Injured Mice from Pulmonary
Infection.
AB - BACKGROUND: Pseudomonas aeruginosa is a major cause of morbidity and mortality
among burn patients, despite antibiotic therapy. There is a need to identify
innate immune defenses that prevent P aeruginosa infection in injured adults in
an effort to find therapeutic alternatives to antibiotics. Here, we tested our
hypothesis that microvesicles (MVs) in bronchoalveolar (BAL) fluid have a role in
the immunity of the lung in response to pathogens. STUDY DESIGN: Microvesicles
were isolated from murine BAL fluid, quantified using Nanoparticle Tracking
Analysis, and injected into burn-injured mice before P aeruginosa infection.
Survival was assessed and BAL bacterial loads enumerated. Neutrophil number and
interleukin 6 activity were determined. Lungs were harvested and sphingosine
(SPH) content analyzed via immunohistochemistry. Antimicrobial effects of MVs and
SPH-enriched MVs were assessed in an in vitro assay. RESULTS: Burn-injured mice
have reduced BAL MV number and SPH content compared with sham. When BAL MVs from
healthy mice are administered to injured mice, survival and bacterial clearance
are improved robustly. We also observed that intranasal administration of MVs
restores SPH levels after burn injury, MVs kill bacteria directly, and this
bacterial killing is increased when the MVs are supplemented with SPH.
CONCLUSIONS: Using a preclinical model, BAL MVs are reduced after scald injury
and BAL MV restoration to injured mice improves survival and bacterial clearance.
The antimicrobial mechanisms leading to improved survival include the quantity
and SPH content of BAL MVs.
PMID- 28690206
TI - Combination of Oral Antibiotics and Mechanical Bowel Preparation Reduces Surgical
Site Infection in Colorectal Surgery.
AB - BACKGROUND: Surgical site infections (SSI) are a common complication after
colorectal surgery. An infection prevention bundle (IPB) was implemented to
improve outcomes. STUDY DESIGN: A standardized IPB that included the
administration of oral antibiotics with a mechanical bowel preparation,
preoperative shower with chlorhexidine, hair removal and skin preparation in
holding, antibiotic wound irrigation, and a "clean-closure" protocol was
implemented in January 2013. Data from the American College of Surgeons NSQIP
were analyzed at a single academic institution to compare pre-IPB and post-IPB
SSI rates. In January 2014, a prospective database was implemented to determine
compliance with individual IPB elements and their effect on outcomes. RESULTS:
For the 24 months pre-IPB, the overall SSI rate was 19.7%. During the 30 months
after IPB implementation, the SSI rate decreased to 8.2% (p < 0.0001). A subset
of 307 patients was identified in both NSQIP and our prospective compliance
databases. Elements of IPB associated with decreased SSI rates included
preoperative shower with chlorhexidine (4.6% vs 16.2%; p = 0.005), oral
antibiotics (3.4% vs 15.4%; p < 0.001), and mechanical bowel preparation (4.4% vs
14.3%; p = 0.008). Patients who received a full bowel preparation of both oral
antibiotics and a mechanical bowel preparation had a 2.7% SSI rate compared with
15.8% for all others (p < 0.001). On multivariate analysis, full bowel
preparation was independently associated with significantly fewer SSI (adjusted
odds ratio 0.2; 95% CI 0.1 to 0.9; p = 0.006). CONCLUSIONS: Implementation of an
IPB was successful in decreasing SSI rates in colorectal surgery patients. The
combination of oral antibiotics with a mechanical bowel preparation was the
strongest predictor of decreased SSI.
PMID- 28690207
TI - Hypophosphatemia after Hepatectomy or Pancreatectomy: Role of the Nicotinamide
Phosphoribosyltransferase.
AB - BACKGROUND: Postoperative hypophosphatemia is common and is associated with a
lower risk of liver failure after hepatectomy, but higher morbidity after
pancreatectomy. Whether different physiologic mechanisms underlie the
hypophosphatemia associated with these very different clinical outcomes is
unclear. This study aims to evaluate the underlying mechanism in postoperative
hypophosphatemia. STUDY DESIGN: We prospectively enrolled 120 patients who
underwent major hepatectomy (n = 30), minor hepatectomy (n = 30), pancreatectomy
(n = 30), and laparotomy without resection (control group, n = 30). Preoperative
and postoperative serum and urinary phosphorus, calcium, and creatinine, as well
as phosphaturic factors, including serum nicotinamide phosphoribosyltransferase
(NAMPT), fibroblast growth factor-23, and parathyroid hormone were measured. In
addition, we evaluated urinary levels of nicotinamide catabolites, N-methyl-2
pyridone-5-carboxamide and N-methyl-4-pyridone-3-carboxamide. RESULTS: We found
that significant hypophosphatemia occurred from postoperative day (POD) 1 to POD
2 in all 4 groups and was preceded by hyperphosphaturia from preoperative day to
POD 1. Phosphate level alterations were associated with a significant increase in
NAMPT levels from preoperative day to POD 2 in all 3 resected groups, but not in
the control group. The fibroblast growth factor-23 levels were significantly
decreased postoperatively in all 4 groups, and parathyroid hormone levels did not
change in any of the 4 groups. Urine levels of N-methyl-2-pyridone-5-carboxamide
and N-methyl-4-pyridone-3-carboxamide decreased significantly in all 4 groups
postoperatively. CONCLUSIONS: This study demonstrates that the mechanism of
hypophosphatemia is the same for both liver and pancreas resections.
Postoperative hypophosphatemia is associated with increased NAMPT. The mechanism
that upregulates NAMPT and its role on disparate clinical outcomes in
postoperative patients warrant additional investigation.
PMID- 28690209
TI - MicroRNAs in skin wound healing.
AB - Wound healing is a fundamental physiological progress to keep the integrity of
the skin. The transition from inflammation to proliferation is a critical step
during skin wound repair process. Impairment of this transition has been known as
a common dominator in the pathophysiology of chronic non-healing wounds.
MicroRNAs (miRNAs) are short non-coding RNAs regulating gene expression. Emerging
evidence has revealed that miRNAs play important roles in both normal skin wound
healing and in the pathogenesis of chronic wounds. We focus on the miRNAs
regulating the inflammation-proliferation transition during wound healing and
propose that these miRNAs may be promising targets for development of more
effective wound therapy.
PMID- 28690211
TI - New perspectives on dandruff and seborrheic dermatitis: lessons we learned from
bacterial and fungal skin microbiota.
AB - The human body is inhabited by complex microbial communities, which positively
impact different aspects of our health, and might also be related to the
development of diseases. Progress in technologies, particularly sequencing
methods and bioinformatics tools, has been crucial for the advances in this
field. Microbial communities from skin can modulate immune response and protect
the host against pathogens, and there are also data supporting their association
with several skin conditions; including dandruff and seborrheic dermatitis. For
decades, they have been thought to be related to Malassezia yeasts; however, the
microbial role has not been elucidated, and their etiology remains poorly
understood. This review discusses the recent findings in dandruff and seborrheic
dermatitis and their relation to the skin microbiota. Data provided new
perceptions to aid in the understanding of these skin disorders, broadening our
view of their etiology and the possible roles of microbial communities in symptom
development.
PMID- 28690212
TI - Focal adhesions in the skin: lessons learned from skin fragility disorders.
AB - Focal adhesions are large multiprotein cell-matrix adhesion complexes, which
regulate multiple cellular functions, such as adhesion and migration. Their
biological significance in skin is underscored by two genetic disorders, the
Kindler syndrome and the interstitial lung disease, nephrotic syndrome and
epidermolysis bullosa, in which mutations affect focal adhesion proteins, kindlin
1 and the integrin alpha3 subunit, respectively. Here we provide an overview of
what we learned from the study of the molecular mechanisms of these diseases.
Emphasis is put on the point of view of the clinician dermatologist.
PMID- 28690213
TI - Scurvy: an "almost" forgotten disease.
PMID- 28690203
TI - Prefrontal cortex executive processes affected by stress in health and disease.
AB - Prefrontal cortical executive functions comprise a number of cognitive
capabilities necessary for goal directed behavior and adaptation to a changing
environment. Executive dysfunction that leads to maladaptive behavior and is a
symptom of psychiatric pathology can be instigated or exacerbated by stress. In
this review we survey research addressing the impact of stress on executive
function, with specific focus on working memory, attention, response inhibition,
and cognitive flexibility. We then consider the neurochemical pathways underlying
these cognitive capabilities and, where known, how stress alters them. Finally,
we review work exploring potential pharmacological and non-pharmacological
approaches that can ameliorate deficits in executive function. Both preclinical
and clinical literature indicates that chronic stress negatively affects
executive function. Although some of the circuitry and neurochemical processes
underlying executive function have been characterized, a great deal is still
unknown regarding how stress affects these processes. Additional work focusing on
this question is needed in order to make progress on developing interventions
that ameliorate executive dysfunction.
PMID- 28690214
TI - [MiR-503 sensitizes human hepatocellular carcinoma cells to cisplatin by
targeting bcl-2].
AB - OBJECTIVE: To investigate effects of miR-503 on cisplatin sensitivity in BEL-7402
cells by targeting of bcl-2.? Methods: MiR-503 and bcl-2 mRNA expression levels
in hepatocellular carcinoma cells were measured by real-time quantitative (qRT)
PCR; Bcl-protein level was detected by Western blot; miR-503 mimics were
transiently transfected to the BEL-7402 cells by liposome transfection; potential
target genes of miR-503 were predicted by Bioinformatics software; miR-503
potential targets were validated by dual luciferase activity; and the cell
viability was measured by MTT assay. ? Results: MiR-503 level was down-regulated
and Bcl-2 protein expression level was up-regulated in BEL-7402 cells compared
with HL-7702 cells. MiR-503 could interact with bcl-2 and inhibit its expression.
Cell vitality with miR-503 transfection was significantly reduced compared to
that in the negative control.? Conclusion: MiR-503 may enhance the sensitivity of
BEL-7402 cells to cisplatin and inhibit the cell proliferation by targeting bcl
2.
PMID- 28690215
TI - [Role of melatonin in calcium overload-induced heart injury].
AB - OBJECTIVE: To investigate the role of melatonin in calcium overload-induced heart
injury.? Methods: Thirty-two rats were divided into 4 groups: a control group
(Control), a melatonin control group (Mel), a calcium overload group (CaP), and a
calcium overload plus melatonin group (Mel+CaP). Isolated Sprague Dawley male rat
hearts underwent Langendorff perfusion. Left ventricular developed pressure
(LVDP) was calculated to evaluate the myocardial performance.
Triphenyltetrazolium chloride staining was used to measure the infarct size of
myocardium. Lactate dehydrogenase (LDH) activity in the coronary flow was
determined. The expressions of caspase-3 and cytochrome c were determined by
Western blot. The pathological morphological changes in myocardial fiber were
analyzed by HE staining.? Results: Compared with the control group, calcium
overload significantly induced an enlarged infarct size (P<0.01), accompanied by
the disordered arrangement of myocardial fiber, up-regulation of cytochrome c and
caspase-3 (P<0.01), and the increased activity of LDH (P<0.01). These effects
were significantly attenuated by 10 MUmol/L melatonin (P<0.01).? Conclusion:
Melatonin can alleviate calcium overload-induced heart injury.
PMID- 28690216
TI - [Plasma level of apelin and carotid atherosclerosis in maintenance hemodialysis
patients].
AB - OBJECTIVE: To determine the plasma level of apelin in patients of maintenance
hemodialysis (MHD) and to explore the relationship between apelin level and
carotid atherosclerosis (AS) in MHD patients.? Methods: A total of 92 MHD
patients and 36 sex- and age-matched healthy subjects were enrolled in this
study. The plasma level of apelin was evaluated by radiation immunoassay; serum
endothelial injury markers including thrombomodulin, von Willebrand factor (vWF),
and CD146, and inflammatory factors including high sensitive C-reactive protein
(hsCRP), IL-6 and TNF-alpha were determined by ELISA. Common Carotid arteries
intima media thickness (CCA-IMT), cross-sectional calculated intima-media area
(cIM area) area and atherosclerotic plaque were measured by non-invasive high
resolution B-mode ultrasonography.? Results: The plasma levels of apelin was
significantly decreased in MHD patients compared with healthy subjects (P<0.01),
accompanied with elevated plasma levels of thrombomodulin, vWF, CD146, hsCRP, IL
6 and TNF-alpha (all P<0.01). The plasma levels of apelinin in MHD patients with
carotid artery plaques were obviously lower than those without plaques [(43.16+/
10.12) pg/mL vs (61.43+/-16.25) pg/mL, P<0.01]. Plasma level of apelin was
inversely related with CCA-IMT and cIM area (r=-0.355 and r=-0.297 respectively,
all P<0.01). Multiple stepwise regression analysis showed that plasma level of
apelin was an independent risk factor for CCA-IMT and cIM area. ? Conclusion: The
plasma apelin in MHD patients might take part in vascular endothelial injury and
the progress of atherosclerosis. It plays an important role in the initiation and
development of uremia associated atherosclerosis through elevating inflammatory
factors including hsCRP, IL-6 and TNF-alpha levels.
PMID- 28690217
TI - [Clinical characteristics and the factors relevant to peritoneal transport
function in patients with continuous ambulatory peritoneal dialysis].
AB - OBJECTIVE: To observe the clinical characteristics with different peritoneal
transport type in patients with continuous ambulatory peritoneal dialysis (CAPD),
and to investigate the factors associated with peritoneal transport function.?
Methods: The clinical data of 158 CAPD patients were analyzed retrospectively.
According to peritoneal equilibration test, a method for evaluation of the
peritoneal transport function, the patients were divided into 2 groups: a high
average and high peritoneal transport group (Group A, n=84) and a low average and
low peritoneal transport group (Group B, n=74). The demographics, clinical
biochemical indexes and the incidence of cardiovascular complications were
compared between the 2 groups. Logistic regression analysis was used to find the
factors relevant to peritoneal transport function.? Results: The level of serum
albumin (ALB) in the Group B was significantly higher than that in the Group A
(P<0.05). The 4 h dialysate/plasma creatinine (D/Pcr), high-sensitivity C
reactive protein (hs-CRP), body mass index (BMI), and the rates of cardiovascular
complications in the Group A were significantly higher than those in the Group B
(P<0.05). Correlation analysis showed that the D/Pcr was positively correlated
with the BMI, serum hs-CRP and cardiovascular complications (r=0.179, 0.373 and
0.426, respectively, P<0.05), while it was negatively correlated with ALB (r=
0.393, P<0.01). Logistic regression analysis showed that the high BMI (OR=1.178,
P<0.05), cardiovascular complications (OR=5.035, P<0.01), and the low serum ALB
(OR=0.852, P<0.01) were the risk factors for high peritoneal transport.?
Conclusion: The serum ALB level, BMI and the cardiovascular complications are
associated with high peritoneal transport, which are useful markers for
predicting the peritoneal transport function before peritoneal dialysis.
PMID- 28690218
TI - [Comparative study between cardiac catheterization intervention therapy and
transthoracic small incision surgery for closure of congenital atrial septal
defect by domestic occluder with echocardiographic monitoring].
AB - OBJECTIVE: To evaluate the safety of cardiac catheterization intervention therapy
and transthoracic small incision surgery in the occlusion bydomestic occluder
under echocardiography guiding in patients with atrial septal defect (ASD).?
Methods: A total of 1 080 patients with ASD in the occlusion by domestic occluder
were analyzed retrospectively, and the interventional treatment were performed in
734 cases through cardiac catheterization intervention therapy and 346 cases
through transthoracic small incision surgery. The patients undergone cardiac
catheterization intervention therapy were guided under the digital substraction
angiography (DSA) and were monitored by transthoracic echocardiography (TTE) in
the whole interventional process, and the efficacy was evaluated with TTE. The
occlusion of transthoracic small incision surgery was guided under the
transesophageal echocardiography (TEE), which was used to monitor the position of
occluder and evaluate the efficacy immediately.? Results: Two kinds of
intervention in the occlusion by domestic occluder had achieved satisfactory
results in patients with ASD. There was no statistically difference in the
longest size of ASD between the 2 intervention methods, while there were
statistically differences in the ratio between ASD longest diameter and atrial
septal length, and the size of the occlusion, and the disparity between the size
of the occluder and ASD longest diameter (D value), respectively (all P<0.05).
When the size of arithmetic mean of the ASD was <30 mm, the success rate of the 2
methods was both 100%. When the size of arithmetic mean of the ASD was >=30 mm,
the success rate was 100% in the transthoracic small incision surgery and 50% in
the cardiac catheterization intervention therapy.? Conclusion: Domestic occluder
is safe. Compared with the imported one, its cost is lower. When the size of the
defects is same, the occlusion is smaller in the transthoracic small incision
surgery compared with that in the cardiac catheterization intervention therapy.
When the size of arithmetic mean of the ASD is >=30 mm, the success rate of the
transthoracic small incision surgery is higher compared with the cardiac
catheterization intervention therapy. When the cardiac catheterization
intervention therapy fails, the transthoracic small incision surgery may be a
better choice.
PMID- 28690219
TI - [Value of postoperative indocyanine green retention rate at 15 minutes combined
with standard remnant liver volume in predicting liver dysfunction after
hepatectomy].
AB - OBJECTIVE: To investigate the value of indocyanine green retention rate at 15
minutes (ICG R15) on postoperative day 3 combined with standard remnant liver
volume (SRLV) in predicting the occurrence of liver dysfunction after
hepatectomyin hepatocellular carcinoma (HCC).? Methods: The clinical data of 61
HCC patients undergone hepatectomy in Xiangya Hospital of Central South
University from January 2015 to February 2016 were collected and analyzed. The
patients were divided into 2 groups: a normal liver function group (n=40) and a
liver dysfunction group (n=21). Univariate analysis was used to evaluate the risk
factors for postoperative liver dysfunction. Logistic regression was used to
assess the independent risk factors for postoperative liver dysfunction, and the
regression equation between independent risk factors and postoperative liver
dysfunction was established. The receiver operating characteristic (ROC) curve
was used to examine the regression equation and compare the value difference in
predicting postoperative liver dysfunction between single and combined
independent risk factors.? Results: Postoperative liver dysfunction occurred in
21 of the 61 patients, with an incidence rate at 34.4%. There was no significant
difference in the time of operation, time of hepatic portal occlusion, volume of
tumor and volume of resected liver between the 2 groups (all P>0.05), but there
were significant differences in the ICG R15 on postoperative day 3,
intraoperative blood loss and SRLV between the 2 groups (all P<0.05). The ICG R15
on postoperative day 3, intraoperative blood loss, SRLV were the risk factors for
postoperative liver dysfunction. Logistic regression analysis showed ICG R15 on
postoperative day 3 and SRLV were the independent risk factors for postoperative
liver dysfunction, and the regression equation between independent risk factors
and postoperative liver dysfunction was as follows: logit(P)=1.277+0.140*ICG R15
on postoperative day 3-5.125*SRLV. The area under the ROC curve of ICG R15 on
postoperative day 3 combined with SRLV was more than that of single ICG R15 and
single SRLV.? Conclusion: ICG R15 on postoperative day 3 and SRLV are the
independent risk factors for postoperative liver dysfunction. The regression
equation, which is established by combination of ICG R15 with SRLV, can predict
the occurrence of postoperative liver dysfunction. The accuracy of ICG R15 on
postoperative day 3 combined with SRLV is better than that of single ICG R15 or
single SRLV.
PMID- 28690220
TI - [Investigation and analysis for current situation and pathogenesis relevant to
pulmonary hypertension].
AB - OBJECTIVE: To investigate the demographic characteristics and the causes for
pulmonary hypertension (PH) in adult patients.? Methods: A total of 2 508 adult
patients diagnosed as PH, who came from the Second Xiangya Hospital of Central
South University from January 2010 to December 2014, were retrospectively
investigated. All subjects underwent the clinical diagnosis, or the
echocardiographic diagnosis, or thetraditional hemodynamic criteria by right
heart catheterization (RHC). The patient's data including hospital numbers,
gender, ages, primary diseases, etc, are collected and analyzed.? Results: In
this study, the number of patients diagnosed as PH was increased year by year.
The median age of 2 508 patients was 47 (18-93) years old, and there were 933
males (37.2%), the ratio of male to female was 1:1.69 (P<0.05). Female was more
common in Class I PH (pulmonary arterial hypertension) and Class II PH (pulmonary
hypertension due to left heart disease)(>70%), but there were more male patients
(74.5%) in Class III PH (pulmonary hypertension due to lung diseases and/or
hypoxia). In our study, 896 cases (35.73%) were the Class I PH, 1 163 cases was
the Class II PH (46.37%), 411 cases was the Class III PH (16.39%), and the Class
IV PH (chronic thromboembolic pulmonary hypertension) and the Class V PH (PH with
unclear and/or multifactorial mechanisms) were diagnosed in 32(1.27%) and 6
patients (0.24%), respectively.The diseases with largest number of patients for
the top 7 primary PH were rheumatic heart disease (1 090, 43.48%), congenital
heart disease (692, 27.60%), chronic obstructive pulmonary disease (358, 14.28%),
connective tissue related disease(156, 6.22%), valvular heart disease (66,
2.63%), idiopathic PH (46, 1.83%) and pulmonary embolism (27, 1.08%).?
Conclusion: Adult PH patients' peak incidence age is 41-50 years old. This
disease is more common among women, and the Class I/II PH are common in women
while the Class III is more common in men. Rheumatic heart disease and congenital
heart disease may be the most common cause for pulmonary hypertension in China,
and chronic obstructive pulmonary disease is the most common cause for the Class
III PH, in which the patients are old.
PMID- 28690221
TI - [Diagnostic value of different detection methods for Mycobacterium tuberculosis
in bronchoalveolar lavage fluid from pulmonary tuberculosis patients].
AB - OBJECTIVE: To investigate the diagnostic value of different detection methods for
Mycobacterium tuberculosis in bronchoalveolar lavage fluid (BALF) from patients
with pulmonary tuberculosis.? Methods: BALF from100 patients in Changsha Central
Hospital from January 2013 to December 2015 was collected. Among 100 patients, 65
cases were clinically diagnosed as tuberculosis, and 35 cases served as control.
BALF smear method, polymerase chain reaction (PCR) and membrane reverse dot blot
(RDB) were used for synchronous detection of Mycobacterium tuberculosis.?
Results: The positive rates by BALF smear method, PCR and RDB were 43.08%, 73.84%
and 92.31%, respectively (P<0.05). Sensitivity, specificity, accuracy, and
negative predictive value for BALF smear were 43.08%, 88.57%, 59.00%, and 45.59%,
respectively; for PCR were 73.85%, 100%, 83.00%, and 67.31%, respectively; for
RDB were 92.31%, 100.00%, 95.00%, and 87.50%, respectively.? Conclusion: The
technique of membrane RDB can not only accurately diagnose Mycobacterium
tuberculosis, but also can rapidly and easily identify the resistance of
Mycobacterium tuberculosis to streptomycin (SM), rifampicin (RFP) and isoniazid
(INH) genotypes. It possesses high clinical value.
PMID- 28690222
TI - [Curative effect of surgery on moyamoya disease: an analysis of 47 patients].
AB - OBJECTIVE: To evaluate the effect of surgery on 47 patients with moyamoya disease
by retrospective analysis.? Methods: A total of 47 patients with moyamoya disease
were enrolled from August, 2010 to According to the improved treatment in August,
2013, all cases were divided into two groups: a pre-improved group and a post
improved group. According to different surgical methods, they were divided into
two subgroups: an indirect revascularization subgroup and a combined
revascularization subgroup.? Results: The cerebral ischemia in 77.4% of patients
was relieved after the surgery. There was significant difference in outcomes of
patients between the pre-improved group and the post-improved group (P<0.05),
while there was no significant difference between the pre-improved indirect
revascularization subgroup and the pre-improved combined revascularization
subgroup. There was also no significant difference between the post-improved
indirect revascularization subgroup and the post-improved combined
revascularization subgroups (P>0.05).? Conclusion: Surgical treatment can improve
the outcomes of patients with moyamoya disease, but there is no significant
difference in surgical effects between indirect and combined revascularization.
PMID- 28690223
TI - [Usage and efficacy of timolol maleate eye drops in treatment of superficial
infantile hemangioma].
AB - OBJECTIVE: To determine drug dose and usage of timolol maleate eye drops in the
treatment of superficial infantile hemangioma.? Methods: A total of 250
superficial hemangioma infants were recruited and assigned into 5 groups (n=50
for each group): an external application group and 4 exterior coating groups (2,
4, 6, 8 times per day). We evaluated the therapeutic effect of different methods
for drug application (external application or exterior coating) and the frequency
for drug administration on superficial infantile hemangioma.? Results: The
external application group (twice a day and 0.5 hour per time) showed better
effect than that in the exterior coating group with twice a day (P<0.001). The
difference in therapeutic effect between the exterior coating group with 6 times
a day and exterior coating group with twice a day or with 3 times a day was
significant (P<0.001). The differences in drug efficacy were not found among the
exterior coating group with 6 times a day, the exterior coating group with 8
times a day, or the external application group with twice a day (All P>0.05).?
Conclusion: Drug dose may affect the therapeutic effect of timolol maleate eye
drops in superficial hemangioma infants, and exterior coating with 6 times a day
may achieve the best curative effect.
PMID- 28690224
TI - [Autologous tissue reconstruction of tarsal plate combined with temporal flap in
repairing full-thickness lower eyelid defect].
AB - OBJECTIVE: To evaluate the clinical effect of combination of autologous tissue
reconstruction of tarsal plate with temporal flap on repair of full-thickness
lower eyelid defect. ? Methods: Eleven patients (11 eyes) underwent hard palate
mucosa or ear cartilage combined the emporal flap with the orbicularis oculi
muscle to repair full-thickness defect of palpebra inferior. Of the 11 patients,
6 had more than 75% eyelid defect area, and 5 had more than 50% eyelid defect
area. ? Results: All 11 eyes closed completely, with no entropion or ectropion,
and returned to normal basically. Postoperative follow-up was performed for 6
months to 5 years, 3 years and 4 months on average. The function and form of
eyelid remained stable. Infection, leakage or contracture was not found on
reconstruction tarsus. ? Conclusion: Reconstruction of eyelid with autogenous
hard palate mucosa or ear cartilage combined the emporal flap with the
orbicularis oculi muscle is a simple, convenient and effective method.
PMID- 28690225
TI - [Grey matter concentration revealed by voxel-based morphometry in individuals
with cognitive vulnerability to depression].
AB - OBJECTIVE: To explore the grey matter concentration in individuals with cognitive
vulnerability to depression.? Methods: Thirty individuals with cognitive
vulnerability to depression and thirty age- and gender-matched healthy controls
were enrolled in this study, and they were subjected to magnetic resonance
imaging (MRI) examination. The grey matter concentration differences were
compared between the two groups by using voxel-based morphometry (VBM) following
MRI.? Results: Individuals with cognitive vulnerability to depression showed
significantly lower grey matter density in bilateral insular, left cerebellum,
right supplementary motor area, and left precentral gyrus than those in the
healthy controls, while the healthy controls showed significantly lower grey
density in the right inferior frontal gyrus, right middle frontal gyrus, and left
cuneus than those in the individuals with cognitive vulnerability to depression.?
Conclusion: Structural brain abnormalities in individuals with cognitive
vulnerability to depression might be the neural basis for cognitive vulnerability
to depression.
PMID- 28690226
TI - [Prevalence of dyslipidemia and its influential factors in 2 028 students from
primary and middle schools in Changsha].
AB - OBJECTIVE: To determine the prevalence of dyslipidemia in students from the
primary and middle schools and the influential factors, and to provide evidence
for the prevention and control of dyslipidemia and relevant chronic diseases in
primary and middle schools. ? Methods: A total of 2 028 students aged 7 to 17
from the primary and middle schools in Changsha were selected by stratified
random cluster sampling. The contents of the study included questionnaire survey,
physical measurement and blood tests for fasting blood triglyceride (TG), total
cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density
lipoprotein cholesterol (HDL-C) levels. Non-high-density lipoprotein cholesterol
(non-HDL-C) level was calculated by TC level minus HDL-C level. Chi-square test
and non-conditional logistic regression model were used to analyze the factors
that contributed to dyslipidemia.? Results: The dyslipidemia rate was 18.6%, and
the abnormal rates of TG, TC, LDL-C, non-HDL-C and HDL-C were 6.8%, 5.6%, 2.3%,
4.2% and 8.6%, respectively. By chi-square test, the dyslipidemia rate in
students with different ages, home locations, BMI groups, central obesity, time
on watching TV or playing computer per day, and daily sleep time was
statistically significant. Non-conditional logistic regression analysis showed
that home location for the city (OR=1.332), overweight (OR=1.548), obesity
(OR=2.201), central obesity (OR=1.695), watching TV or playing computer for more
than 2 hours per day (OR=1.357), daily sleep time longer than 11 hours (OR=2.518)
were the risk factors for dyslipidemia in students from the primary and middle
schools. ? Conclusion: Nearly 1/5 primary and middle school students show
dyslipidemia, which is associated with obesity and other bad behaviors.
PMID- 28690227
TI - [Association between the changes in ideal cardiovascular health status and the
decline of glomerular filtration rates in medical examination people].
AB - OBJECTIVE: To explore the association between the changes in ideal cardiovascular
health (CVH) indices and the renal function.? Methods: The retrospective cohort
study consisted of 837 Chinese individuals from Department of Health Management
in the Third Xiangya Hospital. The general information, anthropometry and blood
biochemistry were obtained for all subjects from 2008 to 2014, respectively. The
6-year changes of 7 ideal CVH metrics defined by American Heart Association and
the estimated glomerular filtration rate (eGFR) were calculated. Linear
regression analysis was used to study the association between the changes in the
ideal CVH metrics and eGFR. Covariance analysis was used to compare the levels of
changes in eGFR stratified by variations of the ideal CVH metrics.? Results:
After 6 years' follow-up, we did not find significant difference in ideal
cardiovascular health indexes between 2014 and 2008 [(3.3+/-1.4) items vs. (3.2+/
1.3) items, respectively] (P<0.05). However, the eGFR in 2014 was significantly
lower than that in 2008 [(99.8+/-22.7) mL/(min.1.73 m2) vs (104.3+/-24.9)
mL/(min.1.73 m2), respectively] (P<0.01). After adjusting for age, sex, history
of hypertension and diabetes, and history of drug usage (antihypertensive,
cholesterol-lowering and blood glucose-lowering medication), the changes in ideal
CVH metrics were positively associated with the changes in eGFR (beta=0.701,
P<0.01). With the improved change in ideal CVH metrics from <=-2 points, -1
point, 0 point, 1 point to >=2 points, the magnitude of decline in eGFR was
gradually decreased , with significant difference (F= 21.71, P<0.01).?
Conclusion: The changes in ideal CVH metrics are an independent risk factor for
changes of eGFR. Positive changes in ideal CVH metrics exert a favorable effect
on renal function evolution.
PMID- 28690228
TI - [Socio-psychological factors relevant to suicidal ideation among patients with
AIDS in Changsha].
AB - OBJECTIVE: To explore the rates of suicide ideation and the relevant factors
among patients with HIV/AIDS (PLWHA) in Changsha for obtaining scientific
evidence to reduce suicidal ideation rates among PLWHA.? Methods: A total of 504
PLWHA were surveyed in an AIDS hospital in Changsha, by using Self-Made Socio
Demographic Scale, Self-rating Depression Scale, Self-rating Anxiety Scale, and
Beck Scale for Suicide Ideation-Chinese Version.? Results: There were 13.9%,
26.6% and 27.2% of PLWHA suffered suicidal ideation in the last week, at the most
depressive moments and all their lives, respectively. Being a gay (OR=4.79, 2.66,
2.37) or with suicide history (OR=8.56, 5.63, 5.56) were the risk factors for
suffering suicidal ideation in the last week, at the most depressive moments and
all their lives. Moreover, anxiety was the risk factor for suffering suicidal
ideation at the most depressive moments and all their lives (OR=3.28, 3.05), and
depression was the risk factor for suffering suicidal ideation in the last week
(OR=4.97).? Conclusion: Among PLWHA, gay is a high risk factor for suffering
suicidal ideation, and suicide history is a risk factor.
PMID- 28690229
TI - [HIV resistance in men who have sex with men: a Meta-analysis].
AB - OBJECTIVE: To assess the prevalence of HIV primary drug resistance and drug
resistance gene mutations among men who have sex with men (MSM).? Methods: We
searched eight electronic databases (CNKI, VIP, CBM, Wanfang Database, PubMed,
Web of Knowledge, Springer, Medline) for the studies of HIV drug resistance
relevant to MSM. Drug resistance and drug resistance mutations data were pooled
and analyzed according to statistical test of homogeneity. Subgroups were further
divided according to sample size, location, race, quality rating score, sampling
time.? Results: Forty-three studies were included in this Meta-analysis. The
pooled rate of total to protease inhibitor (PI), nucleoside reverse transcriptase
inhibitor(NRTI) or non-nucleoside reverse transcriptase inhibitor (NNRTI) were
10.21% (95% CI 8.65% to12.03%), 2.98% (95% CI 2.25% to 3.93%), 4.05% (95% CI
3.14% to 5.21%), 4.42% (95% CI 3.31% to 5.88%), respectively. The pooled rates of
PI major mutation, PI secondary mutations, NRTI mutations and NNRTI mutations
were 0.55% (95% CI 0.38% to 0.80%), 1.31% (95% CI 0.98% to 1.75%), 0.85% (95% CI
0.51% to 1.40%), 1.19% (95% CI 0.70% to 2.01%), 0.79% (95% CI 0.55% to 1.13%),
1.73% (95% CI 1.21% to 2.46%), 0.86% (95% CI 0.61% to 1.21%), 2.24% (95% CI 1.77%
to 2.83%), respectively. Sample size, region, and race were heterogeneous
sources; the rate of resistance mutations and gene mutation rate were different
in different subgroups.? Conclusion: The prevalence of primary drug resistance
among MSM was high in Americas and Europe, and it was gradually increased in
Asia. We should pay attention to the high incidence of PI secondary mutations.
PMID- 28690230
TI - [Comparison between the effect of endoscopic-assisted low temperature plasma and
electric planer on the treatment of adenoid hypertrophy: a Meta-analysis].
AB - OBJECTIVE: To compare the effect of endoscopic-assisted low temperature plasma
(ELTP) and electric planer (EP) on the treatment of adenoid hypertrophy.?
Methods: We searched China National Knowledge Infrastructure (CNKI), Wanfang
Database, Weipu Database, Chinese Biomedical Literature (CMB), PubMed, Embase,
Cochrane Database, and collected the randomized controlled studies regarding the
effect of ELTP and EP on the treatment of adenoid hypertrophy from January 2007
to June 2016. Methodologies were used to evaluate the included studies, and Meta
analysis was performed by Revman 5.2.? Results: Thirteen studies including 1 448
patients fulfilled the study requirement. Seven hundred and twenty-two patients
were treated with ELTP, and 726 patients were treated with EP. The Meta-analysis
showed: compared with EP, ELTP could improve the cure rare (OR=3.19, 95% CI 1.42
to 7.15, P=0.005), reduce the blood loss during surgery (MD=-20.35, 95% CI -20.84
to -19.87, P<0.001), shorten the operation time (MD=-15.71, 95% CI -18.06 to
12.17, P<0.001), and reduce the incidence of complications (OR=0.13, 95% CI 0.06
to 0.30, P<0.001), while there was no difference between the 2 groups in the
postoperative residual rate of adenoid, postoperative hemorrhage rate and the
rate of torus tubarius injury.? Conclusion: Comparing with EP, ELTP shows more
advantages in the adenoidectomy.
PMID- 28690231
TI - [Research progress in epidemiology, diagnosis and treatment for pancreatic
cancer].
AB - Pancreatic cancer is a highly lethal disease in gastrointestinal malignant
tumors. The mortality of pancreatic cancer closely parallels its incidence. Most
patients with pancreatic cancer remain asymptomatic until the disease reaches an
advanced stage. There is no program for screening patients at high risk of
pancreatic cancer. Although CT, MRI, positron emission tomography, endoscopic
ultrasonography, and endoscopic ultrasonography-guided fine-needle aspiration
offer high diagnostic ability for pancreatic cancer, it cannot be found at the
early stage easily. Surgical resection is regarded as the only potentially
curative treatment and adjuvant chemotherapy is given after surgery. This article
reviews epidemiology, risk factors, diagnosis and treatment for pancreatic cancer
by summarizing relevant literature.
PMID- 28690232
TI - [Progress in sleep-disordered breathing in idiopathic pulmonary fibrosis].
AB - Idiopathic pulmonary fibrosis (IPF) is one of the most common idiopathic
interstitial pneumonia. The main symptoms for IPF are dry cough and exertional
shortness of breath, which is worsen gradually with the development of pulmonary
fibrosis. Patients with IPF often suffer from sleep disordered breathing (SDB).
Sleep architecture for these patients including the sleep efficiency, deep sleep,
rapid eye movement sleep and arousal index, are changed, which seriously affects
the quality of life. In the absence of effective therapies, optimizing the
quality of life may become a major therapeutic target for IPF. The diagnosis and
treatment of SDB can significantly improve the quality of life for patients with
IPF.
PMID- 28690233
TI - [Progress in studies on TLR4 signaling pathway and major depressive disorder].
AB - TLR4 signaling pathway plays an important role in regulation of the innate immune
response and the adaptive immune response. Studies have shown that TLR4 signaling
pathway is closely associated with the immune inflammatory process in major
depressive disorder, but the underlying mechanisms are not clear. The
pathophysiological process of depression involves multiple molecule mechanisms
and signal pathways. The change of TLR4 signaling pathways exists in the
peripheral circulation system or the central nervous system of depressive
patients and depression animal models. The activation of TLR4 signaling pathways
is associated with "stress-inflammation-depression" approach and "leaky gut"
hypothesis, however, the relationship of peripheral and central TLR4 signaling
pathways is not clear yet. TLR4 signaling pathway may be potential targets for
the anti-inflammatory treatment of depression.
PMID- 28690234
TI - [PCDH19 gene mutations lead to epilepsy with mental retardation limited to
females in 2 cases and literature review].
AB - Epilepsy with mental retardation limited to females (EFMR) is a syndrome
characterized by early onset heat-sensitive epilepsy of infancy or early
childhood and generally limited to females, which previously reported that the
cadherin gene superfamily subtype protocadherin 19 (PCDH19) gene is its
pathogenic gene. We retrospectively analyzed the clinical data for 2 cases of
EFMR patients with PCDH19 mutation diagnosed by Department of Pediatric Neurology
of Xiangya Hospital, Central South University in 2015. Literature on PubMed, OMIM
and HGMD relevant to this syndrome was reviewed, and the clinical characteristics
were summarized accordingly. The 2 cases are consistent with the typical clinical
manifestations of EFMR caused by PCDH19 mutations. Their seizures are heat
sensitive, with or without screaming, and expressed in various forms. Cognitive
impairment or autism-like performance were often identified in these patients,
hematuria metabolic diseases screening was normal, no abnormal MRI imaging of the
head, and de novo PCDH19 gene mutations were found in their epilepsy gene chip
sequencing. It is noteworthy that this disease is very similar to the clinical
manifestations of the Dravet syndrome due to the mutations of the neurotype
sodium channel alpha1 subunit SCN1A. Therefore, in female patients whose clinical
manifestations resemble to Dravet syndrome but SCN1A gene test were negative,
EFMR with PCDH19 mutation should be taken into consideration. Early PCDH19 gene
testingis of great significance because it not only helps clinicians to
understand and analyze the prognosis of this disease, but also offers genetic
counseling to the parents.
PMID- 28690236
TI - Editor's Introduction.
PMID- 28690237
TI - Taxing Soda: Strategies for Dealing with the Obesity and Diabetes Epidemic.
AB - Over the past several decades, the United States has been experiencing a twin
epidemic of obesity and type 2 diabetes. Recently, advocacy efforts to tax sugary
drinks, place warning labels on soda, improve nutritional labeling, and reduce
sugar overconsumption have swept across the nation to address public health
concerns from sugary drinks that strain our nation's health-care resources. In
this article, the historical and scientific framework of this public health
policy and valuable lessons learned from implementation efforts thus far will be
examined to shape the next steps forward for the movement. Additional goals of
this article are to share a surgeon's perspective about trends in bariatric
surgery and the link between obesity and type 2 diabetes as a result of
peripheral insulin resistance.
PMID- 28690235
TI - [Diagnosis and treatment for one case of elderly diabetes complicated with
Still's disease].
AB - Adult onset Still's disease (AOSD) is a clinical syndrome with multiple organ
failure. The patients normally show intermittent high fever for a long time, a
transient rash, arthritis or joint pain as the main performance, accompanied by
an increase in granulocytes and enlargement in liver, spleen and lymph node. A 71
years-old female patient with type 2 diabetes admitted hospital because of high
fever, skin rash, joint pain and increased granulocyte. After review of the iron
protein, she was diagnosed as AOSD. We found that clinicians need to improve the
understanding for this disease in order to make the early diagnosis, especially
in elderly patients with diabetes mellitus. In such patients, ferritin may not be
high at early time. However, when the symptoms and signs are consistent with
clinical manifestations, and anti-infection treatment effect is poor, we should
pay attention to the disease, and repeated review of ferritin is necessary to
assist the early diagnosis.
PMID- 28690238
TI - Physicians Can Impact Patient Health.
AB - Sugar-sweetened beverages account for nearly half the sugar Americans consume, at
a time when over one-third of the population is obese and over two-thirds are
considered overweight. To help reduce the health risks associated with obesity,
physicians should consider targeting the one culprit most responsible for adding
non-nutritional calories to the diet: sugar-sweetened soda. By helping patients
to reduce or eliminate soda consumption, physicians can make a tremendous
contribution to addressing the obesity crisis in the United States. The author
offers suggestions for helping physicians to provide concrete steps their
patients can use to decrease soda in their diets.
PMID- 28690239
TI - Reassessing Diagrams of Cardiac Mechanics: From Otto Frank and Ernest Starling to
Hiroyuki Suga.
AB - This article explores the importance of diagrams in the history of the
understanding of cardiac function, by comparing Ernest Starling's famous "Law of
the Heart" (1918) with the mathematically based view of cardiac mechanics put
forward by Otto Frank (1897). Whereas Frank's diagrams gained influence in German
cardio-physiological publications, they were widely unknown abroad until 1969,
when Hiroyuki Suga began to present similar approaches for warm-blooded animals
as Frank had done for the frog. Suga succeeded in correlating the pressure volume
area (PVA)-a composite of Frank's work loop plus the area of remaining potential
energy-with the oxygen consumption of the beating heart. With the concept of time
varying elastance as an index of cardiac contractility, Suga's approach became
attractive for clinical applications, and Daniel Burkhoff and colleagues were
able to use these insights for real-time, interactive simulations of the
cardiovascular system. Such tools can be used for exploring basic hemodynamic
principles and, thanks to technical developments of miniature pumps within the
same time frame (Kappaalphaiotarhoomicronsigma, the "right moment," or "the
opportune"), to test the effects of device-based treatment for heart failure.
These outcomes confirm that old analyses of the heart's activity may still be
useful today.
PMID- 28690240
TI - The Research Optimist's Defense.
AB - Several studies suggest that clinical researchers are prone to overestimating the
chance that scientific protocols will succeed, say, by confirming a treatment
hypothesis or reaching recruitment targets. In this essay, we address the
normative question of whether such "unrealistic optimism" is harmful in clinical
research. We entertain five plausible defenses of unrealistic optimism:
agnosticism (optimism cannot be objectively assessed), skepticism (expressions of
unrealistic optimism are difficult to interpret, since researchers are not
accustomed to thinking in terms of probability), contrarianism (unrealistic
optimism is salutary), denialism (any effects of unrealistic optimism are
neutralized by oversight mechanisms), and fatalism (nothing can be done to alter
unrealistic optimism or its effects). Though each argument has force, we find
each insufficient to dispel moral concerns about community-wide unrealistic
optimism in research. We close by describing how each argument might inform the
study and moral evaluation of unrealistic optimism in research.
PMID- 28690241
TI - Libera me, Domine: Christian Roots of Palliative Care.
AB - This article reviews key aspects of the history of the emergence of palliative
care to point out that the language and expressions that are routinely used in
communicating with palliative care patients are often infused with an
unrecognized religious coloration.
PMID- 28690242
TI - Beware Dichotomies.
AB - This essay combines our thoughts concerning the generally destructive practice of
dichotomization with a selective review of the literature supporting our
critique. The apparent simplicity of dichotomous thinking encourages its use even
when a dyadic representation is totally inadequate to understanding complex
situations, and this "simpler is better" mantra continues to stymie our
understanding of many of the world's complexities. The identification and naming
of two distinct, opposing categories often results in their being seen as in
opposition to one another, and that it is somehow incumbent upon us to choose one
or the other. This either/or orientation reinforces the original split, confusing
explanans and explanandum. We begin by considering dichotomization in general
terms, and then turn to brief descriptions of several particular dichotomies.
Some of these persist despite what might well be considered sufficient evidence
to deny their usefulness, and this often deflects attention away from the more
fertile, interesting, and important questions that may be directed to the points
at which they intermingle.
PMID- 28690243
TI - Public Health Approaches and the Human Enhancement Debate.
AB - Some contributors to the cognitive enhancement (CE) debate claim to take a
"public health" approach. However, authors who use this stance end up offering
very different recommendations for CE. Some argue for bioconservatism, others for
transhumanism-all in the name of "public health." This article argues that these
inconsistencies occur because a "public health approach" is far too vague.
Furthermore, public health approaches are silent on an issue that drives a great
deal of the disagreement over CE: differences in anthropology. How one feels
about CE will be influenced by whether one believes there are aspects of human
nature that we ought never tamper with, or whether human nature is just another
rung on the ladder to ever greater forms of life. Whether one sees humanity as
something to be preserved or overcome will drive one's view of CE, and this is an
issue about which public health as far too little to say.
PMID- 28690244
TI - Situating Social Differences in Health and Illness Practices.
AB - This article suggests that in order to understand the social differences evident
in disease prevalence and outcomes, it is necessary to understand what it means
to live with multiple social, physical, and psychological challenges. Drawing on
research in cancer diagnosis, we discuss practices of health, illness, and care
seeking. We suggest that the focus on lifestyle and behavioral change that
dominates contemporary public health interventions should be complemented with a
Weberian circumstantial approach. Acknowledging the situatedness of health and
illness practices may enable us to help our patients gain access to, and benefit
from, the health-care system.
PMID- 28690245
TI - Dear Dr. Peabody.
AB - Reading the following brief piece depends on having some knowledge of the famous
essay to which it refers, Francis W. Peabody's "The Care of the Patient,"
published 90 years ago in the Journal of the American Medical Association (JAMA
88: 877-82). Peabody's essay was based on a talk he gave to Harvard medical
students in 1925, and it was published shortly before his premature death in
1927. At the time, he was highly regarded as a consummate clinician and teacher,
and in his essay, he laments problems he already saw affecting medical practice,
such as the overvaluation of science relative to clinical medicine and a
diminishing spirit of attentiveness to the most deeply human needs of patients.
He deals in an especially astute and compassionate way with the care of patients
suffering from what is now known as somatization disorder. Peabody's essay has
been widely anthologized, is often an assigned reading for medical students, and
has been revered by practitioners and students for almost 100 years. But times
are changing . . .
PMID- 28690246
TI - The Need for Uncertainty: A Case for Prognostic Silence.
AB - Disclosure of prognosis in end-of-life care is a practice that is widely and
increasingly recommended. However, prognostic disclosure is known to be resisted
by many dying persons and by physicians, who instead engage in a "collusion of
silence"-discussing prognosis either not at all or in vague, indirect terms.
Debates about the ethics of prognostic disclosure and non-disclosure have tended
to focus on their relative benefits and harms, or on the psychological
acceptability of prognostic information to dying persons. Unaddressed, however,
is a more fundamental assumption upon which the practice of prognostic disclosure
depends: that prognostic certainty is what dying persons ultimately need. In this
essay I question this assumption. Reflecting on the experience of my father's
recent death, I argue that prognostic certainty is not only unattainable but
existentially irrelevant to many dying persons, and that prognostic uncertainty
can be a greater need. Respect for individuals' existential need for uncertainty
justifies prognostic silence and enables dying persons-as well as the loved ones
and clinicians who care for them-to be open to new possibilities of finding
meaning at the end of life.
PMID- 28690247
TI - Virtue Ethics in Monetized Medicine.
AB - This review essay situates Abraham Nussbaum's The Finest Traditions of Our
Calling (2016) within the contemporary genre of physician memoirs that shade into
critiques of institutional medicine. Nussbaum's primary concern is the
demoralization of medicine as it becomes increasingly monetized; patients are
reduced to body parts and reimbursement schedules. He argues that physicians
continue to have considerable choice in how they practice, despite institutional
constraints. For bioethics, Nussbaum's advocacy of virtue ethics is notable. His
book is a moving testimonial to contemporary problems, but also a manifesto for
possibilities of change at the individual level.
PMID- 28690248
TI - Facing Death.
AB - This review essay reflects on the remarkable best-selling book, When Breath
Becomes Air (2016), by Paul Kalanithi, a young neurosurgeon. The author's moving
narrative displays clinical and existential wisdom and offers rich food for
thought regarding both what it means to be a doctor and the experience of facing
death from metastatic lung cancer.
PMID- 28690249
TI - Paper-based Analytical Devices.
PMID- 28690250
TI - Simultaneous Determination of Felodipine and Metoprolol in Beagle Dog Plasma by
Online SPE-LC-MS/MS and Its Application in a Pharmacokinetic Study.
AB - In order to overcome deficiencies for simultaneously determining felodipine (FDP)
and metoprolol (MPL) with low recovery and low sensitivity, a new online SPE
coupled with the liquid chromatography-tandem mass spectrometry (SPE-LC-MS/MS)
method for the simultaneous quantitative determination of FDP and MPL in beagle
dog plasma was established. The SPE extraction of FDP and MPL was performed on a
Retain PEP Javelin column (10 * 2.1 mm, 5 MUm), while the chromatographic
separation was achieved on a ZORBAX SB-C18 (50 * 2.1 mm, 3.5 MUm) analytical
column. Multiple reaction monitoring operated in the positive ion mode was
adopted in MS detection, and the precursors to the product ion transition values
of m/z 384/338.1, 268/74.2 and 436.2/207.1 were used to measure FDP, MPL and the
internal standard (valsartan). The high throughput, accurate and sensitive method
for FDP and MPL was validated and applied to the bioavailability research of FDP
and MPL in beagle dogs.
PMID- 28690251
TI - Reversible Fluorescence Probe Based on N-Doped Carbon Dots for the Determination
of Mercury Ion and Glutathione in Waters and Living Cells.
AB - An "on-off-on" mode was developed for the detection of mercury ion (Hg2+) and
glutathione (GSH) with high sensitivity and selectivity based on the nitrogen
doped carbon dots (N-CDs) fluorescent probe. The N-CDs were synthesized through
microwave treatment of citric acid and diethylenetriamine for 2 min, and
exhibited excellent fluorescence properties and high quantum yield (27.7%). The
fluorescence intensity of the N-CDs could be significantly quenched by Hg2+ (turn
off). Upon addition of GSH, the fluorescence intensity of the N-CDs-Hg2+ system
could be recovered clearly (turn-on). The limit of detection of Hg2+ and GSH was
23 and 59 nM, respectively. Moreover, the "on-off-on" probe was successfully
applied to the determination of Hg2+ in tap water and water from the Yellow
River. Meanwhile, due to bright luminescence, good biocompatibility and low
cytotoxicity, the N-CDs-based probe was successfully employed as visualizing the
intracellular Hg2+ and GSH sensors in live HeLa cell.
PMID- 28690252
TI - Multivariate Optimization of a Functionalized SBA-15 Mesoporous Based Solid-Phase
Extraction for U(VI) Determination in Water Samples.
AB - A solid-phase extraction based on a functionalized SBA-15, with the Schiff base
ligand, ethylenediaminepropylesalicylaldimine (SBA/EnSA), was developed for the
recovery and preconcentration of trace amounts of uranium(VI) in water samples,
prior to its determination spectrophotometrically using ArsenazoIII. For
optimizing the parameters affecting the adsorption step (pH, adsorbent dose and
adsorption time) and those influencing the desorption process (concentration and
volume of eluent and desorption time), a statistical technique response surface
methodology (RSM) was employed. The limit of detection and the linear dynamic
range for the proposed method were 10 MUg L-1, and 33.5 - 500 MUg L-1,
respectively. The adsorbent showed a high capacity (110.2 mg g-1) and the method
allowed obtaining a preconcentration factor of 67. The inter- and intra-day
relative standard deviations for a solution of 100 MUg L-1 (n = 5) were found to
be 4.8 - 6.2%. The developed method was successfully applied for the
determination of U(VI) in water samples.
PMID- 28690253
TI - Infant Exposure to Bisphenol A Can Be Quantitatively Assessed by a Simply
Improved High-Performance Liquid Chromatography-Tandem Mass-Spectrometry Method.
AB - To quantitatively measure trace levels of bisphenol A (BPA) in infant urine, a
simply improved high-performance liquid chromatography (HPLC)-tandem mass
spectrometry method was developed and validated. In the present work, a ZORBAX SB
C18 column (2.1 * 30 mm, 3.5 MUm) was used for trapping and isolating BPA from
the HPLC mobile phase. The result showed that the trapping column can provide
effective separation from the background BPA to the sample BPA. This method has a
limit of detection (LOD) of 0.048 MUg/L, spiked recoveries 85.4% (0.50 - 10.0
MUg/L), and relative standard deviations of 1.8 - 15.9%. By using its low-LOD
advantage, we firstly reported that Chinese infants (n = 48 with age <6 months)
have been ubiquitously exposed to BPA (detection frequency of 93%) with an median
level of 0.13 MUg/L (ranging from below LOD to 5.04 MUg/L).
PMID- 28690254
TI - MnO2 Nanosheet-based Fluorescence Sensing Platform for Sensitive Detection of
Endonuclease.
AB - A novel fluorescence sensing platform for ultrasensitive detection of S1 nuclease
activity has been constructed based on MnO2 nanosheets and FAM labeled single
stranded DNA (FAM-ssDNA). In this system, MnO2 nanosheets were found to have
different adsorbent ability toward ssDNA and mono- or oligonucleotide fragments.
FAM-ssDNA could adsorb on MnO2 nanosheets and resulted in significant
fluorescence quenching through fluorescence resonance energy transfer (FRET),
while mono- or oligonucleotide fragments could not adsorb on MnO2 nanosheets and
still retained strong fluorescence emission. With the addition of S1 nuclease,
FAM-ssDNA was cleaved into mono- or oligonucleotide fragments, which were not
able to adsorb on MnO2 nanosheets and the fluorescence signal was never quenched.
The different fluorescence intensity allowed for examination of S1 nuclease
activity. The developed method can detect S1 nuclease activity in the range of 0
20 U mL-1 with a detection limit of 0.05 U mL-1. Benefits of the system include
less time-consuming processes and more simple design compared to other
endonuclease assays. Satisfactory performance for S1 nuclease in complex samples
has been successfully demonstrated with the system. The developed assay could
potentially provide a new platform in bioimaging and clinical diagnosis.
PMID- 28690255
TI - Rapid Detection of Diazepam Injection Based on Surface Enhanced Raman
Spectroscopy.
AB - Diazepam injection was detected based on a droplet surface enhanced Raman
spectroscopy (SERS) platform, which overcomes the disadvantages of the poor
uniformity and time-consuming sample treatment process of the conventional "drop
and dry" detection strategy. The Raman peak positions of diazepam injection were
determined and identified, they are mainly located in the 689, 1002, 1170 and
1598 cm-1, etc. Different concentrations of diazepam injection were detected. It
was found that the intensity of 1002 cm-1 increases linearly with concentration
in the range from 0.05 to 10 MUg/mL and the linear correlation coefficient is
0.988. The limit of detection can reach 0.05 MUg/mL. The SERS method is easy,
fast and efficient. The results are accurate and reliable. It has favorable
application potential in the detection of diazepam injection.
PMID- 28690256
TI - Sensitive Electrochemical Capsaicin Sensor Based on a Screen Printed Electrode
Modified with Poly(sodium 4-styrenesulfonate) Functionalized Graphite.
AB - A sensitive capsaicin sensor was constructed based on a poly(sodium 4
styrenesulfonate) functionalized graphite modified screen printed electrode (PSS
Grp/SPE) in this study. The PSS-Grp and poly(diallyldimethylammonium chloride)
functionalized graphite (PDDA-Grp) were easily synthesized by interacting Grp
with PSS and PDDA through sonication, and resulted in negative and with positive
charges on the surface, respectively. The prepared PSS-Grp and PDDA-Grp were
characterized by scanning electron microscopy (SEM), transmission electron
microscopy (TEM) and ultraviolet and visible spectroscopy (UV-vis). The
electrochemical performance of PSS-Grp in a 50 MUM capsaicin solution presented a
current density of 33 MUA cm-2, which was much higher than the PDDA-Grp of 1.5
MUA cm-2. Our study showed that capsaicin could interact better with strong
negative charges on the PSS-Grp/SPE surface to give a higher electrochemical
response. The direct electrochemical sensing of capsaicin was achieved at PSS
Grp/SPE using differential pulse stripping voltammetry (DPSV) under the optimized
conditions.
PMID- 28690257
TI - Anodic Stripping Voltammetry for the Determination of Trace Cr(VI) with
Graphite/Styrene-Acrylonitrile Copolymer Composite Electrodes.
AB - A square-wave anodic stripping voltammetry (SWASV) for the determination of trace
amounts of hexavalent chromium Cr(VI) at a graphite/styrene-acrylonitrile
(Graphite-SAN) copolymer composite electrode is described. This method involves a
preconcentration step whereby the trace Cr(VI) was cathodically reduced to
Cr(III) on an electrode surface in an acetate buffer (pH 5), followed by an
anodic stripping technique with a square-wave voltammetric mode. It has been
shown that the analytical sensitivity is significantly improved at the Graphite
SAN copolymer composite electrode in comparison with the conventional glassy
carbon electrode, due to the strong interaction between Cr(III) and the nitrile
end group of the SAN copolymer. The SWASV response was characterized with respect
to the pH, deposition potential, possible interferences, etc. Under the optimal
conditions, the stripping peak height linearly increased with the concentration
of Cr(VI) in a range from 0 to 150 ng mL-1 with a correlation coefficient of
0.997, and a detection limit of 4.2 ng mL-1 was achieved based on signal-to-noise
ratio of about 3. The Graphite-SAN composite electrode exhibited some interesting
advantages, such as high mechanical rigid, easy surface renewable, higher
sensitivity and better peak resolution in comparison with the results at
conventional glassy carbon electrodes. They have been applied to the
determination of Cr(VI) in real water samples with satisfactory recoveries.
PMID- 28690258
TI - A Practical Application of Solid-phase Extraction Using a Syringe Filled with
Sorbent for the Determination of Lead and Cadmium in Water.
AB - In this study, at first the synthesis of 3-chloro-2-hydroxypropyl methacrylate
ethylene glycole dimethacrylate co-polymer beads and its modification with tris(2
aminoethyl) amine is described. Characterization of the polymer was done by FTIR
and SEM. The functional co-polymer was filled in a disposable pipet tip and
tightly connected to a 50-mL syringe for the separation and the enrichment of
lead and cadmium prior to their determination by flame atomic absorption
spectrometry. The sample and then the eluate were subsequently drawn and
discharged to retain and desorb lead and cadmium by means of the syringe,
respectively. Both analytes were quantitatively retained at pH 4 and eluted using
3.0 mol L-1 of HNO3 at flow rates of approximately 10 mL min-1. Under the optimum
conditions, the enrichment factors of up to 50-fold both elements could be
obtained by drawing and discharging 250 mL (5 * 50 mL) of the sample, and then 5
mL of the eluent. The recoveries were >90%. The limits of detection (3sigma; N =
10 of blank) for Pb and Cd were 0.0034 and 0.0016 mg L-1 for a 50-fold
enrichment, respectively. The analyte concentrations in a certified waste water
reference agreed within the certified values in the 95% confidence range.
PMID- 28690259
TI - Determination of the Electrostatic Potential of Oil-in-Water Emulsion Droplets by
Combined Use of Two Membrane Potential-Sensitive Dyes.
AB - The fluorescence behaviors of potential-sensitive dyes including anionic
DiBAC4(3) (denoted by dye A), DiSBAC2(3) (dye B), and zwitterionic di-4-ANEPPS
(dye C) were studied in oil-in-water (O/W) emulsions. In this study, the
equilibrium Galvani potential difference (DeltaOWphieq) of the O/W-emulsion
droplets was controlled by changing the ratio of the concentrations of
electrolytes added to the O (=1,2-dichloroethane) and W phases. When using an
adequate combination of the dyes, i.e., B and C, we could observe that the ratio
of their fluorescence peak intensities was changed from 1.08 to 1.38, depending
on the change of (DeltaOWphieq from 26 to 73 mV. It is desirable to apply this
method to study the potential-dependent ion or electron-transfer reactions
occurring at vesicles or liposomes, and also to biomembranes.
PMID- 28690260
TI - Rapid Quantification of N-Methyl-2-pyrrolidone in Polymer Matrices by Thermal
Desorption-GC/MS.
AB - Analysis of a residual solvent in polymeric materials has become an important
issue due to the increased regulations and standards for its use. N-Methyl-2
pyrrolidone (NMP) is a solvent widely used in many industries and restricted as
one of the chemicals under EU REACH regulations due to its potential harmful
effects. In this study, thermal desorption-gas chromatography/mass spectrometry
(TD-GC/MS) is applied for the quantitative analysis of NMP with the use of a
polymer-coated sample cup. By using the polymer-coated sample cup, the
vaporization of NMP was prevented during waiting time before TD-GC/MS analysis.
The calibration curve for the TD method showed good linearity (correlation
coefficient, r2 = 0.9998) and precision values (below 5.3% RSD). NMP recovery
rates in different polymer matrices (PS, PMMA and PVC) were in the range of 98.8
to 106.6% with RSD values below 5.0%. The quantification result (600 mg NMP/kg
PVC) for the blind NMP carrying sample in a PVC matrix by TD-GC/MS was higher
than that (532 mg NMP/kg PVC) by solvent extraction-GC/MS method.
PMID- 28690261
TI - Improvement of a Phosphate Ion-selective Microsensor Using
Bis(dibromophenylstannyl)methane as a Carrier.
AB - An ionophore-doped sensing membrane phosphate (PO4) microsensor based on
bis(dibromophenylstannyl)methane (Bis microsensor) is described. The Bis
microsensor showed a Nernstian response. The response of the Bis microsensor was
log-linear down to a monohydrogen phosphate ion (HPO42-) concentration of 0.5 MUM
(corresponding to 1.0 MUM of orthophosphate at pH 7.2), whereas the detection
limit of PO4-microsensors based on trialkyl/aryltin chloride was 50 MUM of HPO42
. The Bis microsensor showed excellent selectivity for HPO42- against nitrite,
nitrate, chloride, bicarbonate and sulfate, as compared with PO4 microsensors
based on trialkyl/aryltin chloride. Dissolved oxygen, which is known to interfere
with the response of a previously developed cobalt-based potentiometric solid
state PO4 microsensor, had no effect on the response of the ionophore-doped
sensing membrane-type microsensors described herein. Only OH- (i.e., pH)
interfered with the ionophore-doped sensing membrane-type microsensors.
PMID- 28690262
TI - Colorimetric Detection of Mercury(II) Ion in Aqueous Solution Using Silver
Nanoparticles.
AB - Novel green-chemistry synthesis of silver nanoparticles (AgNPs) is introduced as
a low-cost, rapid and easy-to-use analytical method for mercury ion detection.
Aqueous fruit extract of water apple (Syzygium aqueum) was used for the first
time as bioreductant to synthesize stable AgNPs. The prepared AgNPs have a
yellowish-brown color with a surface plasmon resonance peak at 420 nm. The
addition of Hg(II) ions then changes the AgNPs color to colorless. The color
change was in proportion to the concentration of Hg(II) ions. The presence of
other metal ions in the system was also evaluated. The proposed method shows good
selectivity and sensitivity towards Hg(II) ions. Using UV-visible
spectrophotometry, the detection limit of the developed method was 8.5 * 10-7 M.
The proposed method has been successfully applied for determination of Hg(II)
ions in tap and lake water samples with precision better than 5%.
PMID- 28690263
TI - Direct Electron Transfer-type Bioelectrocatalysis of Peroxidase at Mesoporous
Carbon Electrodes and Its Application for Glucose Determination Based on Bienzyme
System.
AB - Non-catalytic direct electron transfer (DET) signal of Compound I of horseradish
peroxidase (POD) was first detected at 0.7 V on POD/carbon nanotube mixture
modified electrodes. Excellent performance of DET-type bioelectrocatalysis was
achieved with POD immobilized with glutaraldehyde on Ketjen Black (KB)-modified
electrodes for H2O2 reduction with an onset potential of 0.65 V (vs. Ag | AgCl |
sat. KCl) without any electrode surface modification. The POD-immobilized KB
electrode was found to be suitable for detecting H2O2 with a low detection limit
(0.1 MUM at S/N = 3) at -0.1 V. By co-immobilizing glucose oxidase (GOD) and POD
on the KB-modified electrode, a bienzyme electrode was constructed to couple the
oxidase reaction of GOD with the DET-type bioelectrocatalytic reduction of H2O2
by POD. The amperometric detection of glucose was performed with a high
sensitivity (0.33 +/- 0.01 MUA cm-2 MUM-1) and a low detection limit (2 MUM at
S/N = 3).
PMID- 28690264
TI - Diffusion-controlled Mediated Electron Transfer-type Bioelectrocatalysis Using
Microband Electrodes as Ultimate Amperometric Glucose Sensors.
AB - We performed numerical simulations on an extremely fast, mediated, electron
transfer-type bioelectrocatalytic reaction using a microband electrode. The
simulations under fast-enzyme-kinetics conditions predicted that the decrement of
the current density by increaseing the microband thickness would effectively
improve the upper limit of detection. These predictions were accurate for an
ultrathin-ring with thickness of 100 nm and gold leaf with thickness of 10 MUm
electrodes, acting as novel amperometric glucose sensors with FAD-dependent
glucose dehydrogenase. The gold leaf electrode provided pseudo-steady-state
currents which were proportional to the glucose concentration up to a
concentration of 20 times higher than the mediator concentration.
PMID- 28690265
TI - Raman Imaging Analysis of Local Crystal Structures in LiCoO2 Thin Films Calcined
at Different Temperatures.
AB - Local crystalline structures of LiCoO2 nanothin film cathodes in a lithium ion
battery have been spectroscopically elucidated through confocal Raman imaging
analysis at high spatial resolution of several hundred nanometers. A significant
difference in the crystalline structure is found between the nanometric thin
films and bulk powders. Thermally induced local decomposition of LiCoO2 into an
impurity phase on the films has also been revealed along with the mechanism of
the temperature-triggered decomposition process. Moreover, frequency-based Raman
imaging enables us to locally probe spatial separation between stoichiometric
(LiCoO2) and non-stoichiometric (Li1-xCoO2, 0 < x < 1) crystal phases on the thin
films. Such local crystalline analysis is a promising approach to provide new
insights into the degradation mechanism of lithium-ion batteries, which would
result in improving the performance of thin film-based lithium ion batteries.
PMID- 28690266
TI - On-site Determination of Trace Arsenic by Reflection-Absorption Colorimetry of
Molybdenum Blue Collected on a Membrane Filter.
AB - An on-site determination method for trace arsenic has been developed by
collecting it as molybdenum blue (MB) in the presence of
tetradecyldimethylbenzylammonium chloride on a mixed cellulose ester membrane
filter and by measuring reflection absorbance (RA) of MB on the filter using a
laboratory-made palm-top size reflection-absorbance colorimeter with a red light
emitting diode. The value of RA was proportional to the amount of arsenic up to
0.5 MUg with a detection limit of 0.01 MUg. The proposed method was successfully
applied to soil extract and hot-spring water samples.
PMID- 28690267
TI - Determination of Menadione by Liquid Chromatography-Tandem Mass Spectrometry
Using Pseudo Multiple Reaction Monitoring.
AB - This study aimed to develop a menadione (MD) determination method employing
liquid chromatography-tandem mass spectrometry (LC-MS/MS) using a pseudo multiple
reaction monitoring (MRM) technique, wherein two quadrupoles are used to monitor
the same ion. Detection limits of 40 and 2 pg were obtained for MD and its
deuterium-labeled form, respectively, whereas MD intra- and inter-assay
coefficient of variation values were determined as 5.4 - 8.2%, with the
corresponding recoveries equaling 90.5 - 109.6%. The developed method enables
determination of MD in urine, plasma, cell extract, and culture media,
demonstrating that pseudo multiple reaction monitoring can achieve quantification
of compounds forming no suitable product ions, such as MD.
PMID- 28690269
TI - Selection criteria for statistical significance test in confirmatory
pharmacological studies.
PMID- 28690270
TI - Estimation of relative potency using parallel line analysis.
PMID- 28690271
TI - In-house statistical training for research scientists in drug discovery.
PMID- 28690272
TI - Review of relevance between metal homeostasis and neurodegenerative disease.
PMID- 28690273
TI - Current status and promising future of pharmaceutical cocrystals in development
of oral dosage forms.
PMID- 28690274
TI - Application and comparison of analytical methods for data of nonclinical
exploratory pharmacological studies.
PMID- 28690275
TI - Preclinical and clinical properties of elbasvir (ERELSA(r) Tablets 50 mg) and
Grazoprevir (GRAZYNA(r) Tablets 50 mg), novel therapeutic agents for hepatitis C.
PMID- 28690276
TI - Pharmacological characteristics and clinical outcomes of ponatinib (Iclusig(r)),
a third-generation tyrosine kinase inhibitor.
PMID- 28690277
TI - Preoperative diagnostic algorithm of primary thyroid lymphoma using ultrasound,
aspiration cytology, and flow cytometry.
AB - The aims of this report were to clarify the diagnostic significance of ultrasound
(US), fine needle aspiration cytology (FNAC), and flow cytometry for primary
thyroid lymphoma, and to establish a preoperative diagnostic algorithm of primary
thyroid lymphoma. We retrospectively examined US, FNAC, and flow cytometry in 43
patients with benign lymphoproliferative lesions and 32 patients with primary
thyroid lymphoma, who underwent US, FNAC, and flow cytometry at Kuma Hospital
between May 2012 and December 2015. Primary thyroid lymphomas included 27 mucosa
associated lymphoid tissue lymphomas, 4 diffuse large B-cell lymphomas, and 1
follicular lymphoma. Flow cytometry had the highest specificity (88.4%) and
sensitivity (75.0%). The specificity of US was the lowest (32.6%). Both the
positive predictive value (90.5%) and negative predictive value (94.7%) were the
highest for FNAC. A scoring system was defined as follows: US, low suspicion 0,
intermediate suspicion 1, and high suspicion 2; FNAC, benign 0, undetermined 1,
malignant 2; and flow cytometry, 0.33< kappa/lambda ratio <3 0, kappa/lambda
ratio <=0.33 2, and kappa/lambda ratio >=3 2. We propose that a score >=4
indicates the need for thyroid resection for diagnosing primary thyroid lymphoma.
In such a situation, the case of diffuse large B-cell lymphoma, which was
aggressive, was not excluded. Approximately one-fifth of mucosa-associated
lymphoid tissue lymphomas may be overlooked, but the patients could be followed
up with because of an indolent course.
PMID- 28690278
TI - Cellular and soluble components decrease the viable pathogen counts in milk from
dairy cows with subclinical mastitis.
AB - The present study was undertaken to clarify the factors that reduce the viable
pathogen count in milk collected from the udders of subclinical mastitic cows
during preservation. Milk was centrifuged to divide somatic cells (cellular
components, precipitates) and antimicrobial peptides (soluble components,
supernatants without fat layer); each fraction was cultured with bacteria, and
the number of viable bacteria was assessed prior to and after culture. In 28.8%
of milk samples, we noted no viable bacteria immediately after collection; this
value increased significantly after a 5-hr incubation of milk with cellular
components but not with soluble components (48.1 and 28.8%, respectively). After
culture with cellular components, the numbers of bacteria (excluding
Staphylococcus aureus and Streptococcus uberis) and yeast decreased dramatically,
although the differences were not statistically significant. After cultivation
with soluble components, only yeasts showed a tendency toward decreased mean
viability, whereas the mean bacterial counts of S. uberis and T. pyogenes tended
to increase after 5-hr preservation with soluble components. These results
suggest that most pathogens in high somatic cell count (SCC) milk decreased
during preservation at 15 to 25 degrees C, due to both the cellular components
and antimicrobial components in the milk. Particularly, the cellular components
more potently reduced bacterial counts during preservation.
PMID- 28690280
TI - Subclinical Hypothyroidism, Pregnancy and the Fukushima Nuclear Power Plant
Accident.
PMID- 28690279
TI - Towards a preventive strategy for neosporosis: challenges and future perspectives
for vaccine development against infection with Neospora caninum.
AB - Neosporosis is caused by the intracellular protozoan parasite Neospora caninum.
This major disease-causing pathogen is responsible for inducing abortion in
cattle, and these adverse events occur sporadically all over the world, including
Japan. Currently, there are no vaccines on the market against infection with N.
caninum. Because live and attenuated vaccines against N. caninum have had safety
and effectiveness issues, development of a next-generation vaccine is urgently
required. To develop a vaccine against neosporosis, my laboratory has been
focused on the following: 1) understanding the host immune responses against
Neospora infection, 2) identifying vaccine antigens and 3) developing an
effective antigen-delivery system. The research strategy taken in my laboratory
will have strong potential to progress current understanding of the pathogenesis
of N. caninum infection and promote development of a novel subunit vaccine based
on the specific vaccine antigen with an antigen-delivery system for controlling
neosporosis.
PMID- 28690281
TI - Women with Subclinical Hypothyroidism Are at Low Risk of Poor Pregnancy Outcome
in Japan.
AB - Maternal subclinical hypothyroidism may be associated with adverse pregnancy
outcomes, although not consistently across regions. Here, we sought to determine
the effect of elevated thyroid-stimulating hormone (TSH) on pregnancy outcomes in
Japanese women without known medical complications. TSH was determined by dried
blood spots at 8-20 weeks of gestation, and 3.0-10.0 MUU/mL of TSH was considered
as elevated TSH (eTSH). A retrospective study involving 167 cases of eTSH was
conducted. Five hundred and seventy eight of controls with normal TSH and without
thyroid antibodies were selected. We compared a composite adverse maternal
outcome comprised of spontaneous abortion, premature delivery, gestational
diabetes mellitus (GDM), placental abruption, and pregnancy-induced hypertension,
as well as composite adverse neonatal outcome including stillbirths, heavy for
date, light for date, and a low Apgar score (< 7) at 5 minutes between two
groups. The incidence of GDM was significantly higher in eTSH (p < 0.01);
however, composite adverse maternal and neonatal outcome did not differ between
groups (p = 0.19 and p = 0.50, respectively). Although 27 out of 167 cases in
eTSH have antibodies, composite adverse outcome did not differ between eTSH with
antibodies and controls (p = 0.64 and p = 0.50, respectively). Additionally,
composite adverse maternal and neonatal outcome did not differ between the group
larger than the median of TSH in eTSH (n = 81) and controls (p = 0.43 and p =
0.98, respectively). Thus, elevated TSH is not associated with overall adverse
pregnancy outcomes in women without known medical complications.
PMID- 28690282
TI - Targeted Next-Generation Sequencing Newly Identifies Mutations in Exostosin-1 and
Exostosin-2 Genes of Patients with Multiple Osteochondromas.
AB - Multiple osteochondromas (MO) is one of the most common benign bone tumors in
humans with an autosomal dominant hereditary mode. MO is a genetic heterogeneity
disease with variable number and size of osteochondromas, as well as changeable
number and location of diseased bones. Mutations in Exostosin-1/Exostosin-2
(EXT1/EXT2) genes are the main molecular basis of MO. EXT1 and EXT2 genes encode
exostosin 1 and exostosin 2, respectively, both of which are transmembrane
glycosyltransferases that elongate the chains of heparin sulfate (HS) at HS
proteoglycans (HSPGs). HSPGs are considered to be involved in regulating the
proliferation and differentiation of chondrocytes. Owing to large size of
EXT1/EXT2 genes and lack of mutation hotspots, molecular diagnosis of MO is
challenging. Here, we applied targeted next-generation sequencing (t-NGS) in
mutation screening of EXT1/EXT2 genes for 10 MO patients. The results were
compared and validated with Sanger sequencing. Overall, nine mutations identified
by t-NGS were confirmed with Sanger sequencing, excluding two variants of false
positive, suggesting the reliability of mutation screening by t-NGS. The nine
mutations identified by t-NGS include two missense mutations (EXT1: c.1088G>A and
c.2120C>T), one splicing mutation (EXT2: c.744-1G>T), and six nonsense mutations
(EXT1: c.351C>G, c.1121G>A, and c.1843_1846dup; EXT2: c.67C>T, c.561delG, and
c.575T>A). In summary, our paper provides the primary data of the application of
t-NGS in MO molecular diagnosis, including six newly identified mutations (EXT1:
c.1843_1846dup, c.1088G>A, c.351C>G, and c.2120C>T and EXT2: c.744-1G>T and
c.575T>A), which further enrich the mutation database of MO from the Chinese
population.
PMID- 28690283
TI - Postmortem Computed Tomographic Analysis of Death Caused by Oral Drug
Intoxication.
AB - Traditional autopsy has changed little in the past century. In Japan, the rate of
forensic autopsy in cases of unusual death is very low. Therefore, multi-slice
computed tomography (CT) has been used to obtain imaging data instead of or in
addition to autopsy in suspicious forensic cases. In our institute, postmortem
multi-slice CT has been performed since 2009, and by 2014 there were over 1,000
cases. Our extensive experience with postmortem CT shows that in many cases of
death by drug overdose, stomach contents exhibit high X-ray absorption. This
article reviews the relationship between CT findings of stomach contents and
toxicological analysis results in 23 cases of death by drug overdose. All cases
(12 females and 11 males, aged 44 +/- 11 years) known to have orally ingested
drugs were included in this study. We assessed the slices of all stomach areas on
consecutive axial CT images. Twenty cases (87%) showed high X-ray absorption in
the stomach, while the other three did not demonstrate radio-dense stomach
contents even though drug analysis detected lethal concentrations of drugs in the
blood. In conclusion, drugs were frequently, but not always, visualized as
contents with high X-ray absorption in the stomach. Postmortem gastric CT images
can provide useful information in cases of oral drug intoxication if there are
empty drug packages or a suicide note at the death scene. However, precise
determination of the cause of death requires full autopsy in cases where there is
no indication of suicide at the death scene.
PMID- 28690284
TI - Association Between Waist-to-Height Ratio and Endothelial Dysfunction in Patients
With Morbidity - A Report From the FMD-J Study.
AB - BACKGROUND: Waist circumference (WC), waist-to-height ratio (WHtR) and body mass
index (BMI) are known as easy anthropometric markers of abnormal obesity and
screening tools for predicting cardiovascular outcomes, but which indices are
best is unclear. We therefore investigated the superiority and association
between each index and low flow-mediated dilatation (FMD) as a surrogate marker
for cardiovascular outcomes in patients with morbidity in a large Japanese
prospective cohort.Methods and Results:A total of 1,645 Japanese patients who had
coronary artery disease and hypertension or diabetes mellitus were enrolled, and
1,087 of them were analyzed. The high-WHtR group (>=0.5) showed greater morbidity
and increased inflammation in association with atherosclerosis compared with the
low-WHtR group. High WHtR and advanced age were identified as predictors of low
FMD (odds ratio (OR) 1.39, 95% confidence interval (CI) 1.02-1.88, P=0.037 and OR
1.55, 95% CI 1.19-2.01, P=0.001, respectively). However, WC was not associated
with that risk in either sex (male: OR 1.37, 95% CI 0.97-1.93, P=0.076; female:
OR 1.08, 95% CI 0.68-1.73, P=0.74), and no association was evident between high
BMI and low FMD (OR 0.92, 95% CI 0.71-1.19, P=0.54). CONCLUSIONS: WHtR offers a
superior predictor of decreased FMD than other anthropometric indices, and
progression of arteriosclerosis might be detected more sensitively. Further study
is needed to investigate the relationship between cardiovascular mortality and
WHtR.
PMID- 28690285
TI - Myocardial Bridges on Coronary Computed Tomography Angiography - Correlation With
Intravascular Ultrasound and Fractional Flow Reserve.
AB - BACKGROUND: Myocardial bridges (MB) are commonly seen on coronary CT angiography
(CCTA) in asymptomatic individuals, but in patients with recurrent typical angina
symptoms, yet no obstructive coronary artery disease (CAD), evaluation of their
potential hemodynamic significance is clinically relevant. The aim of this study
was to compare CCTA to invasive coronary angiography (ICA), including
intravascular ultrasound (IVUS), to confirm MB morphology and estimate their
functional significance in symptomatic patients.Methods and Results:We
retrospectively identified 59 patients from our clinical databases between 2009
and 2014 in whom the suspicion for MB was raised by symptoms of recurrent typical
angina in the absence of significant obstructive CAD on ICA. All patients
underwent CCTA, ICA and IVUS. MB length and depth by CCTA agreed well with length
(0.6+/-23.7 mm) and depth (CT coverage) as seen on IVUS. The product of CT length
and depth (CT coverage), (MB muscle index (MMI)), >=31 predicted an abnormal
diastolic fractional flow reserve (dFFR) <=0.76 with a sensitivity and
specificity of 74% and 62% respectively (area under the curve=0.722).
CONCLUSIONS: In patients with recurrent symptoms of typical angina yet no
obstructive CAD, clinicians should consider dynamic ischemia from an MB in the
differential diagnosis. The product of length and depth (i.e., MMI) by CCTA may
provide some non-invasive insight into the hemodynamic significance of a
myocardial bridge, as compared with invasive assessment with dFFR.
PMID- 28690286
TI - A Case of Recurrent Pneumothorax Associated with Birt-Hogg-Dube Syndrome Treated
with Bilateral Simultaneous Surgery and Total Pleural Covering.
AB - Birt-Hogg-Dube syndrome is an autosomal dominant genetic disorder characterized
by a triad of skin tumors, renal tumors, and multiple pulmonary cysts. Our
patient was a 40-year-old man with a history of recurrent bilateral pneumothorax
and a family history of pneumothorax. The patient visited our department with
chest pain and was diagnosed with left pneumothorax based on a chest X-ray.
Thoracic computed tomography (CT) showed multiple cysts in both lungs. We
performed thoracoscopic bilateral bullectomy with curative intent. Intraoperative
observation showed numerous cysts in the lung apex, interlobular region, and
mediastinum. We resected the cysts that we suspected to be responsible for the
symptoms and ligated the lesions, and then performed total pleural covering.
After surgery, genetic testing was performed. The result enabled us to diagnose
Birt-Hogg-Dube syndrome in this patient. Although the patient has developed
neither recurrent pneumothorax nor any renal tumors, to date, long-term
monitoring is necessary.
PMID- 28690288
TI - Genetic characterization of an H2N2 influenza virus isolated from a muskrat in
Western Siberia.
AB - Thirty-two muskrats (Ondatra zibethicus) were captured for surveillance of avian
influenza virus in wild waterfowl and mammals near Lake Chany, Western Siberia,
Russia. A/muskrat/Russia/63/2014 (H2N2) was isolated from an apparently healthy
muskrat using chicken embryos. Based on phylogenetic analysis, the hemagglutinin
and neuraminidase genes of this isolate were classified into the Eurasian avian
like influenza virus clade and closely related to low pathogenic avian influenza
viruses (LPAIVs) isolated from wild water birds in Italy and Sweden,
respectively. Other internal genes were also closely related to LPAIVs isolated
from Eurasian wild water birds. Results suggest that interspecies transmission of
LPAIVs from wild water birds to semiaquatic mammals occurs, facilitating the
spread and evolution of LPAIVs in wetland areas of Western Siberia.
PMID- 28690287
TI - Stroke volume variation (SVV) and pulse pressure variation (PPV) as indicators of
fluid responsiveness in sevoflurane anesthetized mechanically ventilated
euvolemic dogs.
AB - Changes in stroke volume variation (SVV) and pulse pressure variation (PPV) in
response to fluid infusion were experimentally evaluated during vecuronium
infusion and sevoflurane anesthesia in 5 adult, mechanically ventilated,
euvolemic, beagle dogs. Sequential increases in central venous pressure (CVP; 3
7[baseline], 8-12, 13-17, 18-22 and 23-27 mmHg) were produced by infusing
lactated Ringer's solution and 6% hydroxyethyl starch solution. Heart rate
(beats/min), right atrial pressure (RAP, mmHg), pulmonary arterial pressure (PAP,
mmHg), pulmonary capillary wedge pressure (PCWP, mmHg), transpulmonary
thermodilution cardiac output (TPTDCO, l/min), stroke volume (SV, ml/beat),
arterial blood pressure (ABP, mmHg), extravascular lung water (EVLW, ml),
pulmonary vascular permeability index (PVPI, calculated), SVV (%), PPV (%) and
systemic vascular resistance (SVR, dynes/sec/cm5) were determined at each
predetermined CVP range. Heart rate (P=0.019), RAP (P<0.001), PAP (P<0.001), PCWP
(P<0.001), TPTDCO (P=0.009) and SV (P=0.04) increased and SVR (P<0.001), SVV
(P<0.001) and PPV (P<0.001) decreased associated with each stepwise increase in
CVP. Arterial blood pressure, EVLW, PVPI and the arterial partial pressures of
oxygen and carbon dioxide did not change. The changes in SVV and PPV directly
reflected the fluid load and the minimum threshold values for detecting fluid
responsiveness were SVV >=11% and PPV >=7% in dogs.
PMID- 28690289
TI - Systemic mycobacteriosis caused by 'Mycobacterium avium subspecies hominissuis'
in a 14-month-old Japanese black beef steer.
AB - A 14-month-old Japanese black beef steer presented with severe chronic diarrhea
and emaciation and was euthanized. Postmortem examination showed thickened and
corrugated intestinal mucosa and enlarged granulomatous mesenteric lymph nodes
with caseating necrosis. Numerous epithelioid cells and multinucleated giant
cells infiltrated in the lamina propria and the submucosal tissue of the
intestines. These cells were also observed in the systemic organs. Many acid-fast
bacilli were detected in the cytoplasm of these cells and were identified as
'Mycobacterium avium subsp. hominissuis' (Mah) on the basis of the results of
molecular examinations and immunohistochemistry. These findings indicate that Mah
can cause systemic mycobacteriosis, and this unique infection needs to be
distinguished from Johne's disease and tuberculosis in cattle.
PMID- 28690290
TI - Rescue of an intracellular avirulent Rhodococcus equi replication defect by the
extracellular addition of virulence-associated protein A.
AB - Rhodococcus equi is a facultative intracellular bacterium that can escape from
bactericidal mechanisms associated with phagocytosis. Virulence-associated
protein A (VapA), encoded on a virulence-associated plasmid, is essential for
intracellular survival in macrophages, but its function is not known. Here, we
show that the extracellular addition of recombinant glutathione S-transferase
(GST)-VapA fusion protein rescued the intracellular replication defect of a
mutant lacking the vapA gene. Furthermore, the virulence-plasmid-cured strain
could also multiply to nearly wild-type levels by the addition of GST-VapA. The
present data suggest that VapA can alter the intraphagocytic environment, thereby
affecting its suitability for the growth of R. equi.
PMID- 28690291
TI - Geminin deletion in pre-meiotic DNA replication stage causes spermatogenesis
defect and infertility.
AB - Geminin plays a critical role in cell cycle regulation by regulating DNA
replication and serves as a transcriptional molecular switch that directs cell
fate decisions. Spermatogonia lacking Geminin disappear during the initial wave
of mitotic proliferation, while geminin is not required for meiotic progression
of spermatocytes. It is unclear whether geminin plays a role in pre-meiotic DNA
replication in later-stage spermatogonia and their subsequent differentiation.
Here, we selectively disrupted Geminin in the male germline using the Stra8
Cre/loxP conditional knockout system. Geminin-deficient mice showed atrophic
testes and infertility, concomitant with impaired spermatogenesis and reduced
sperm motility. The number of undifferentiated spermatogonia and spermatocytes
was significantly reduced; the pachytene stage was impaired most severely.
Expression of cell proliferation-associated genes was reduced in Gmnnfl/Delta;
Stra8-Cre testes compared to in controls. Increased DNA damage, decreased Cdt1,
and increased phosphorylation of Chk1/Chk2 were observed in Geminin-deficient
germ cells. These results suggest that geminin plays important roles in pre
meiotic DNA replication and subsequent spermatogenesis.
PMID- 28690292
TI - Atrial Fibrillation on Admission Is Related With Higher Mortality in ST-Segment
Elevation Myocardial Infarction Patients.
AB - The prognostic significance of atrial fibrillation (AF) on mortality in ST
segment elevation myocardial infarction (STEMI) patients is not clearly
understood. To elucidate the clinical significance of AF on mortality for 1 year
in STEMI patients, we retrospectively analyzed the Korea Acute Myocardial
Infarction Registry (KAMIR) database, which spans January 2008 to September 2010
and includes 14,329 patients with acute myocardial infarction. We selected 5,556
patients with marked ECG rhythm (NSR, normal sinus rhythm or AF) on emergency
room arrival, < 12 hours of symptom onset, and who underwent primary percutaneous
coronary intervention (PCI) within 90 minutes of arriving at the hospital.
Patients who had been followed-up for at least for 1 year were analyzed (2,636 of
NSR, 119 of AF). At enrollment, AF patients were older (70.7 versus 65.5 years, P
< 0.001) and had lower systolic blood pressure (120.6 versus 125.9 mmHg, P =
0.050), a higher heart rate (80.4 versus 75.6/minute, P = 0.009), and a higher
rate of Killip III, IV (25.0 versus 14.2%, P = 0.002). Patients with AF showed
clearly higher all-cause mortality (22.7 versus 9.5%, HR 2.51, 95%CI 1.68~3.76, P
< 0.001) and cardiac death rate (17.7 versus 7.5%, HR 2.49, 95%CI 1.59~3.90, P <
0.001) at 1 year after admission compared patients with NSR. AF induced
significantly higher all-cause mortality and cardiac mortality rate in STEMI
patients who were appropriately revascularized with primary PCI compared to NSR
at 1 year.
PMID- 28690293
TI - Tracheal Compression Caused by a Mediastinal Hematoma After Interrupted Aortic
Arch Surgery.
AB - Congenital abnormalities of the aortic arch include interrupted aortic arch
(IAA), coarctation of the aorta (CoA), and double aortic arch (DAA). Aortic arch
repair is difficult and postoperative complications are common. However,
postoperative tracheobronchial stenosis with respiratory insufficiency is an
uncommon complication and is usually caused by increased aortic anastomotic
tension. We report here a case of tracheal compression by a mediastinal hematoma
following IAA surgery. The patient underwent a repeat operation to remove the
hematoma and was successfully weaned off the ventilator.In cases of
tracheobronchial stenosis after aortic arch surgery, airway compression by
increased aortic anastomotic tension is usually the first diagnosis considered by
clinicians. Other causes, such as mediastinal hematomas, are often ignored.
However, the severity of symptoms with mediastinal hematomas makes this an
important entity.
PMID- 28690294
TI - Unusual Coronary Sinus Tumor in a Pregnant Woman.
AB - Primary coronary sinus tumors are extremely rare. Herein, we present a case of a
pregnant woman with a primary myxoma in the coronary sinus (CS), which was
diagnosed by echocardiography and computed tomography. We reviewed the literature
and found two other primary CS tumors. We summarized the gender, ages, symptoms,
diagnostic methods, associated anomalies, treatments, histologic findings, and
outcomes of the 3 cases. Dyspnea was a common symptom of all 3 patients.
Diagnostic methods included echocardiography, computed tomography, magnetic
resonance imaging, and coronary angiography. Associated anomalies included
coronary artery fistulas, coronary sinus orifice atresia with persistent left
superior vena cava, intra-cardiac invasion, and pericardial effusion. The 3
histologic types of primary CS tumor were haemangioma, lymphoma, and myxoma. The
3 patients received proper treatment and had good therapeutic outcomes.
PMID- 28690295
TI - High Frequency of Acute Adverse Cardiovascular Events After Lung Transplantation
in Patients With Pulmonary Arterial Hypertension Receiving Preoperative Long-Term
Intravenous Prostacyclin.
AB - Adverse cardiovascular events after lung transplantation (LT) increase the
mortality in patients with pulmonary arterial hypertension (PAH). Long-term
intravenous prostacyclin is the usual treatment in severe patients with PAH, but
it may increase the risk of hemorrhage due to its antiplatelet aggregation effect
or thrombocytopenia. We investigated the impact of length of intravenous
prostacyclin therapy on acute adverse cardiovascular events including hemorrhagic
complication after LT. We retrospectively compared the incidence of adverse
events (death, intrathoracic hematoma and bleeding, cardiac congestion or shock,
cerebral infarction and pulmonary embolism) within 30 days after LT between
no/short-term (median 0.6 years, n = 13) and long-term (median 3.7 years, n = 15)
intravenous prostacyclin groups. There were no differences in the dose of
intravenous prostacyclin and pulmonary artery pressure between the two groups.
Among 22 adverse events (0.8 +/- 1.1 events/patient), 4 events occurred in the
no/short-term intravenous prostacyclin group and 18 occurred in the long-term
intravenous prostacyclin group. The event rate per patient in the long-term
intravenous prostacyclin group (1.2 +/- 1.3 events/patient) was significantly
higher than that in the no/short-term intravenous prostacyclin group (0.3 +/- 0.5
events/patient) (P < 0.05). Intrathoracic hematoma and bleeding was the most
frequent adverse event (9 events, 41%). Preoperative long-term intravenous
prostacyclin therapy increases acute adverse cardiovascular events after LT in
patients with PAH.
PMID- 28690296
TI - Prevalence and Spectrum of NKX2-5 Mutations Associated With Sporadic Adult-Onset
Dilated Cardiomyopathy.
AB - Dilated cardiomyopathy (DCM), the most common form of primary myocardial disease,
is a leading cause of congestive heart failure and the most common indication for
heart transplantation. Recently, NKX2-5 mutations have been involved in the
pathogenesis of familial DCM. However, the prevalence and spectrum of NKX2-5
mutations associated with sporadic DCM remain to be evaluated. In this study, the
coding regions and flanking introns of the NKX2-5 gene, which encodes a cardiac
transcription factor pivotal for cardiac development and structural remodeling,
were sequenced in 210 unrelated patients with sporadic adult-onset DCM. A total
of 300 unrelated healthy individuals used as controls were also genotyped for
NKX2-5. The functional effect of the mutant NKX2-5 was investigated using a dual
luciferase reporter assay system. As a result, two novel heterozygous NKX2-5
mutations, p.R139W and p.E167X, were identified in 2 unrelated patients with
sporadic adult-onset DCM, with a mutational prevalence of approximately 0.95%.
The mutations were absent in 600 referential chromosomes and the altered amino
acids were completely conserved evolutionarily across species. Functional assays
revealed that the NKX2-5 mutants were associated with significantly reduced
transcriptional activity. Furthermore, the mutations abrogated the synergistic
activation between NKX2-5 and GATA4 as well as TBX20, two other cardiac key
transcription factors that have been causally linked to adult-onset DCM. This
study is the first to associate NKX2-5 loss-of-function mutations with enhanced
susceptibility to sporadic DCM, which provides novel insight into the molecular
etiology underpinning DCM, and suggests the potential implications for the
genetic counseling and personalized treatment of the DCM patients.
PMID- 28690297
TI - Successful Complete Revascularization With PCI Using Super-Low Volume of Contrast
Medium in a Patient With Three-Vessel Disease Including 2 Chronic Total
Occlusions With Severe Renal Dysfunction.
AB - The most important factor for preventing contrast-induced nephropathy (CIN)
during percutaneous coronary intervention (PCI) in patients with severe renal
dysfunction is to minimize the contrast volume. Herein, we report a successful
case of complete revascularization after 3 separate PCI procedures using a super
low volume of contrast medium in a patient with 3-vessel disease, including two
chronic total occlusions (CTOs). A 70-year-old man having exertional angina
despite maximal medical therapy was referred to our hospital. He had severe renal
dysfunction (estimated glomerular filtration rate 19 mL/minute/1.73 m2). Coronary
angiography, in which a total volume of 15 mL (over 3 injections) of contrast
medium was used after hydration with normal saline, demonstrated 2 CTOs in the
proximal left circumflex artery (LCX) and the proximal right coronary artery
(RCA) as well as focal stenosis in the mid left descending artery (LAD). Because
the patient refused coronary artery bypass grafting, we opted for
revascularization with PCI, divided into 3 procedures. We made full use of
microcatheter tip injection and evaluation with intravascular ultrasound and
achieved complete revascularization with a total of 31 mL of contrast medium: 9
mL for RCA, 6 mL for LAD, and 16 mL for LCX, without the occurrence of CIN.
Additionally, we present tips for performing PCI using super-low contrast medium.
PMID- 28690298
TI - Comparison of Empiric Isolation and Conventional Isolation of Superior Vena Cava
in Addition to Pulmonary Vein Isolation on the Outcome of Paroxysmal Atrial
Fibrillation Ablation.
AB - Radiofrequency catheter ablation (RFCA) in the treatment of AF is currently based
on pulmonary vein isolation (PVI). Some studies have investigated the efficacy of
empiric SVC isolation (SVCI) in addition to conventional PVI in order to improve
success rates and reduce recurrence rates. However, the results of the studies
have given conflicting data.We performed a meta-analysis to evaluate the efficacy
and safety of the empiric SVCI compared with conventional SVCI for paroxysmal
atrial fibrillation (PAF) ablation.We searched MEDLINE, EMBASE, the Web of
Science, and the Cochrane Database from the period January 1986 to August 2016
and identified qualified studies. The primary clinical outcome was the recurrence
rate of atrial tachyarrhythmias, and the secondary clinical outcomes were
procedure time, fluoroscopy time, and complications.We identified 3 randomized
controlled trials (RCTs) and one nonrandomized, observational study (nROS)
involving 245 patients with empiric SVCI and 269 patients with conventional SVCI.
The empiric SVCI group had a lower recurrence rate of atrial tachyarrhythmia
after a single procedure compared with the conventional SVCI group (16.7% versus
29.4%, OR: 0.48, 95%CI: 0.31 to 0.74, P = 0.0009). There was no significant
difference in fluoroscopic time (P = 0.22), procedure time (P = 0.32), or
clinical complications (P = 0.33) between the two groups.Empiric SVCI is more
effective than conventional SVCI in terms of the long-term outcomes of PAF
patients after a single PVI procedure, with the same fluoroscopic time, procedure
time, and clinical complications.
PMID- 28690299
TI - Optical Coherence Tomography Assessment of Glucose Fluctuation Impact on the
Neointimal Proliferation After Stent Implantation in a
Diabetic/Hypercholesterolemic Swine Model.
AB - The aim of the present study was to investigate the effects of glucose
fluctuation on neointimal proliferation after stent implantation by optical
coherence tomography (OCT) in a diabetic/hypercholesterolemic (DM/HC) swine
model.A total of 24 everolimus-eluting stents (EES) were implanted in the right
coronary artery (RCA) of the animals using a 20% overstretch ratio. The 24 swines
were divided into a DM-high glucose fluctuation (HGF) group (n = 8), DMlow
glucose fluctuation (LGF) group (n = 8), and a control group (n = 8). Percent
diameter stenosis (%DS), late loss (LL), percent area stenosis (%AS), and
neointimal thickness (NIT) were analyzed. The differences in neointimal
characteristics and circulating oxidative stress and inflammation biomarkers were
assessed and measured.At 28 days, the highest values of %DS, LL, %AS, and NIT
were achieved in the HGF group followed by the LGF group (P < 0.05) and the
control group (P < 0.05). The highest frequency of the heterogeneous pattern was
in the HGF group followed by the LGF group (P < 0.05) and the control group (P <
0.05). This was also the case for the oxidative stress and inflammation
biomarkers.DM might have a deleterious impact on neointimal proliferation after
EES implantation in this DM/HC swine model. The extent of glucose fluctuation may
be related to the degree of neointimal proliferation and this needs to be further
confirmed by long-term follow-up and histology.
PMID- 28690300
TI - Contemporary In-Hospital and Long-Term Outcomes of Surgical Management for Fungal
Endocarditis.
AB - Fungal endocarditis (FE) is a rare and fatal disease. The contemporary in
hospital and long-term surgical outcomes of FE have not been adequately
evaluated. This study describes our experience with the surgical management of
FE.Eight FE patients who underwent surgery in our center from January 2004 to
November 2016 were included in this study. Seven had fungal prosthetic valve
endocarditis (PVE) and one fungal native valve endocarditis (NVE). The Bentall
operation, Cabrol operation, and mitral valve replacement were performed in 4, 3,
and 1 patient, respectively. The overall in-hospital mortality rate was 25%
(2/8). The follow-up was completed in all surviving patients and the mean follow
up time was 55.5 +/- 63.3 (range, 1-154) months. Two late deaths occurred at 2
months and 4 months after discharge. The other patients recovered well during the
follow-up.FE is a devastating disease and surgical treatment has acceptable in
hospital and long-term mortality rates.
PMID- 28690301
TI - Rapid Identification Method of Omphalotus japonicus by Polymerase Chain Reaction
Restriction Fragment Length Polymorphism (PCR-RFLP).
AB - Omphalotus japonicus is a poisonous mushroom that grows in Japan. It can be
mistaken for edible mushrooms (Shiitake, Hiratake and Mukitake), and if ingested,
it causes food poisoning within 30 min to 1 hr. We established a rapid detection
method using PCR-RFLP to identify O. japonicus by restriction digestion of the
amplified ITS region. By using Sau96I, Bpu10I, SfcI or DrdI/HincII as a
restriction enzyme, it was possible to rapidly identify and discriminate O.
japonicus based on the fragment length. This study also provided a short PCR-RFLP
system comprising amplification and digestion of a short 200-bp DNA fragment
within the ITS region. The system could identify and discriminate O. japonicus
after in vitro gastric digestion of native and heated mushroom samples as a model
of food poisoning. In addition, a confirmatory assay using real-time PCR was
developed to achieve more sensitive detection of O. japonicus.
PMID- 28690302
TI - A Rapid Dialysis Method for Analysis of Artificial Sweeteners in Foods (2nd
Report).
AB - Following the previous report, a rapid dialysis method was developed for the
extraction and purification of four artificial sweeteners, namely, sodium
saccharide (Sa), acesulfame potassium (AK), aspartame (APM), and dulcin (Du),
which are present in various foods. The method was evaluated by the addition of
0.02 g/kg of these sweeteners to a cookie sample, in the same manner as in the
previous report. Revisions from the previous method were: reduction of the total
dialysis volume from 200 to 100 mL, change of tube length from 55 to 50 cm,
change of dialysate from 0.01 mol/L hydrochloric aqueous solution containing 10%
sodium chloride to 30% methanol solution, and change of dialysis conditions from
ambient temperature with occasional shaking to 50C with shaking at 160 rpm. As a
result of these revisions, the recovery reached 99.3-103.8% with one hour
dialysis. The obtained recovery yields were comparable to the recovery yields in
the previous method with four hour dialysis.
PMID- 28690303
TI - PCR-Based Method for the Detection of Toxic Mushrooms Causing Food-Poisoning
Incidents.
AB - In this study, species-specific identification of five toxic mushrooms,
Chlorophyllum molybdites, Gymnopilus junonius, Hypholoma fasciculare,
Pleurocybella porrigens, and Tricholoma ustale, which have been involved in food
poisoning incidents in Japan, was investigated. Specific primer pairs targeting
internal transcribed spacer (ITS) regions were designed for PCR detection. The
specific amplicons were obtained from fresh, cooked, and simulated gastric fluid
(SGF)-treated samples. No amplicons were detected from other mushrooms with
similar morphology. Our method using one-step extraction of mushrooms allows
rapid detection within 2.5 hr. It could be utilized for rapid identification or
screening of toxic mushrooms.
PMID- 28690304
TI - Determination of Residues of Phenicol Drugs in Ayu (Plecoglossus altivelis) by LC
MS/MS.
AB - An analytical method for the determination of residues of 3 phenicol drugs
(chloramphenicol, thiamphenicol and florfenicol) in Ayu (Plecoglossus altivelis)
by LC-MS/MS was developed. We used the whole body of Ayu, including the bones and
internal organs, in addition to muscle. Phenicols were extracted with 90%
acetonitrile and an aliquot of the crude extract was cleaned up on a Florisil
column (2 g), followed by defatting with n-hexane. The acetonitrile extract was
evaporated and the solvent was replaced with phosphate buffer, then the extract
was purified on a hydroxylated styrene-divinylbenzene copolymer column (200 mg).
Finally, sample solution was passed through a deproteination cartridge filter
with a lipid removal function. Chloramphenicol was quantitated by means of a
calibration curve corrected with salogate standard (chloramphenicol-d5) and
thiamphenicol and florfenicol were quantitated based on absolute calibration
curves. This method was validated in accordance with the notification of the
Ministry of Health, Labour and Welfare of Japan. As a result of the validation
study, the trueness, repeatability and within-laboratory reproducibility were 85
103, 5-13 and 8-13%, respectively. This method is useful for inspecting residues
of 3 phenicol drugs in whole body of Ayu efficiently. Moreover, when
chloramphenicol and thiamphenicol are detected by this method, the quantitated
value is applicable to decide the compliance of the sample with the
specifications and standards of the Food Sanitation Law.
PMID- 28690305
TI - Determination of Nonvolatile Amines in Foods by Improved Dansyl Derivatization
Reaction.
AB - An analytical method for the determination of nonvolatile amines (putrescine,
cadaverine, histamine, tyramine, and spermidine) in foods was developed, using an
improved dansyl derivatization technique. The five amines were extracted from
food with 1% trichloroacetic acid. Three milliliter of extract was applied to a
polymer-based strong cation exchange resin mini-column, which was washed with 5
mL of water, and eluted with 5 mL of 1 mol/L potassium carbonate solution. The
eluate was dansylated, then 5 mL of toluene was added with shaking. The toluene
layer was evaporated. The residue was taken up in 1 mL of acetonitrile and shaken
with 1 mL of 5% proline in 1 mol/L potassium carbonate solution. The upper
acetonitrile layer was collected, filtered, and subjected to HPLC. The limits of
quantitation for putrescine and cadaverine in the samples were both 0.2 MUg/g;
those of spermidine, tyramine, and histamine were 0.8, 2.0, and 5.0 MUg/g,
respectively. The average recoveries of the five amines from nine foods exceeded
80%.
PMID- 28690306
TI - Evaluation of New Cleanup Agents for Analysis of Pesticide Residues in Tea.
AB - We evaluated the effectiveness of new cleanup agents (S-NH2 and S-Si) compared
with other previously reported cleanup agents (octadecylsilane, graphitized
carbon, aminopropyl and silica gel) for removal of interfering substances such as
catechin and caffeine prior to analysis of pesticide residues in tea. S-NH2 and S
Si were highly efficient in removal of catechin and caffeine, respectively.
Recoveries of 80 pesticides using S-NH2 and S-Si were tested, and more than 70%
of pesticides showed recovery greater than 70%. These results indicate that S-NH2
and S-Si agents will be useful for analysis of pesticide residues in tea.
PMID- 28690307
TI - Analyses of Acidic Tar Dyes in High-Protein Foods and Examination of Extraction
and Clean-Up Methods for Various Foods.
AB - Extraction and clean-up methods were examined for the analysis of acidic tar dyes
in various high-protein foods. 1% Aqueous ammonia followed by ethanol, 1% aqueous
ammonia-ethanol (1 : 1) mixture, and 1% aqueous ammonia-tetrahydrofuran (1 : 1)
mixture were used in sequence for boiled fish paste (kamaboko), pounded fish cake
(hanpen), and sausage. The sausage extract was centrifuged at low temperature to
solidify and remove the contained fat. Salted cod roe with red pepper was
extracted twice with 1% aqueous ammonia-ethanol (1 : 1) mixture, followed by
extraction with 1% aqueous ammonia-tetrahydrofuran (1 : 1) mixture. A
divinylbenzene-N-vinylpyrrolidone copolymer column was used for the clean-up of
xanthen dyes. In the case of clogging-prone samples, the same type of large
particle-size column was used. A polyamide column was used for clean-up of the
other dyes. When each dye was added at 5 MUg/g in the foods, recoveries from
kamaboko, hanpen, and sausage ranged from 76 to 102%, and the average recovery
from the two types of salted cold roe with red pepper ranged from 45 to 98%.
PMID- 28690308
TI - Survey on Metals Contained in Stainless Steel Kitchenware and Tableware.
AB - Stainless steel kitchenware and tableware on sale in Japan were investigated.
Surface elemental composition ratios of 172 samples were analyzed by the
fluorescence X-ray method. High levels of manganese (9.59-20.03%)were detected in
17 samples. This finding was confirmed by ICP analysis. Next, we conducted
migration tests. Samples conformed to the Italian Specific Migration Limits.
Moreover, lead and antimony were not detected in these samples, in accordance
with the Japanese Food Sanitation Law.
PMID- 28690309
TI - Survival in Young Patients With Noncompaction May Not Only Depend on Cardiac But
Also on Neuromuscular Comorbidity.
PMID- 28690310
TI - Survival in Young Patients With Noncompaction May Not Only Depend on Cardiac But
Also on Neuromuscular Comorbidity - Reply.
PMID- 28690311
TI - Predictors of Long-Term Mortality and Frequent Re-Hospitalization in Patients
with Acute Decompensated Heart Failure and Kidney Dysfunction Treated with Renin
Angiotensin System Blockers.
AB - BACKGROUND Assessment of risk for all-cause mortality and re-hospitalization is
an important task during discharge of acute heart failure (AHF) patients, as they
warrant different management strategies. Treatment with optimal medical therapy
may change predictors for these 2 end-points in AHF patients with renal
dysfunction. The aim of this study was to evaluate the predictors for long-term
outcome in AHF patients with kidney dysfunction who were discharged on optimal
medical therapy. MATERIAL AND METHODS The study was conducted retrospectively.
The study group consisted of 225 AHF patients with moderate-to-severe kidney
dysfunction, who were hospitalized at Kocaeli University Hospital Cardiology
Clinic and who were prescribed beta-blockers and ACE-inhibitors or angiotensin II
receptor blockers at discharge. Clinical, echocardiographic, and biochemical
predictors of the composite of total mortality and frequent re-hospitalization
(>=3 hospitalizations during the follow-up) were assessed using Cox regression
and the predictors for each end-point were assessed by competing risk regression
analysis. RESULTS Incidence of all-cause mortality was 45.3% and frequent
readmissions were 49.8% in a median follow-up of 54 months. The associates of the
composite end-point were age, NYHA class, respiration rate on admission, eGFR,
hypoalbuminemia, mitral valve E/E' ratio, and ejection fraction. In competing
risk regression analysis, right-sided HF, hypoalbuminemia, age, and uric acid
appeared as independent associates of all-cause mortality, whereas NYHA class, NT
proBNP, mitral valve E/E' ratio, and uric acid were predictors for re
hospitalization. CONCLUSIONS Predictors for all-cause mortality in AHF with
kidney dysfunction treated with optimal therapy are mainly related to advanced HF
with right-sided dysfunction, whereas frequent re-hospitalization is associated
with volume overload manifested by increased mitral E/E' ratio and NT-proBNP
levels.
PMID- 28690312
TI - Wolff-Parkinson-White Syndrome with Ventricular Hypertrophy in a Brazilian
Family.
AB - BACKGROUND PRKAG2 syndrome diagnosis is already well-defined as Wolff-Parkinson
White syndrome (WPW), ventricular hypertrophy (VH) due to glycogen accumulation,
and conduction system disease (CSD). Because of its rarity, there is a lack of
literature focused on the treatment. The present study aimed to describe
appropriate strategies for the treatment of affected family members with PRKAG2
syndrome with a long follow-up period. CASE REPORT We studied 60 selected
individuals from 84 family members (32 males, 53.3%) (mean age 27+/-16 years).
Patients with WPW and/or VH were placed in a group of 18 individuals, in which 11
(61.1%) had VH and WPW, 6 (33.3%) had isolated WPW, and 1 (5.6%) had isolated VH.
Palpitations occurred in 16 patients (88.9%), chest pain in 11 (61.1%), dizziness
in 13 (72.2%), syncope in 15 (83.3%), and dyspnea in 13 (72%). Sudden cardiac
death (SCD) occurred in 2 (11.1%), and 2 patients with cardiac arrest (CA) had
asystole and pre-excited atrial flutter-fibrillation (AFL and AF) as the
documented mechanism. Transient ischemic attack (TIA) and learning/language
disabilities with delayed development were observed. Genetic analysis identified
a new missense pathogenic variant (p.K290I) in the PRKAG2 gene. Cardiac
histopathology demonstrated the predominance of vacuoles containing glycogen
derivative and fibrosis. The treatment was based on hypertension and diabetes
mellitus (DM) control, antiarrhythmic drugs (AD), anticoagulation, and
radiofrequency catheter ablation (RCA). Six patients (33.3%) underwent pacemaker
implantation (PM). CONCLUSIONS The present study describes the clinical treatment
for a rare cardiac syndrome caused by a PRKAG2 mutation.
PMID- 28690313
TI - The HDAC inhibitor panobinostat (LBH589) exerts in vivo anti-leukaemic activity
against MLL-rearranged acute lymphoblastic leukaemia and involves the
RNF20/RNF40/WAC-H2B ubiquitination axis.
AB - MLL-rearranged acute lymphoblastic leukaemia (ALL) represents an aggressive
malignancy in infants (<1 year of age), associated with poor outcome. Current
treatment intensification is not further possible, and novel therapy strategies
are needed. Notably, MLL-rearranged ALL is characterised by a strongly
deregulated epigenome and shows sensitivity to epigenetic perturbators. Here we
demonstrate the in vivo efficacy of the histone deacetylase inhibitor
panobinostat (LBH589) using xenograft mouse models of MLL-rearranged ALL.
Panobinostat monotherapy showed strong anti-leukaemic effects, extending survival
and reducing overall disease burden. Comprehensive molecular analyses in vitro
showed that this anti-leukaemic activity involves depletion of H2B ubiquitination
via suppression of the RNF20/RNF40/WAC E3 ligase complex; a pivotal pathway for
MLL-rearranged leukaemic maintenance. Knockdown of WAC phenocopied loss of H2B
ubiquitination and concomitant cell death induction. These combined data
demonstrate that panobinostat cross-inhibits multiple epigenetic pathways,
ultimately contributing to its highly efficacious targeting of MLL-rearranged
ALL.
PMID- 28690314
TI - Evolution of NPM1-negative therapy-related myelodysplastic syndromes following
curative treatment of NPM1-mutant AML.
PMID- 28690316
TI - Early life immunology: Fetal DCs - born to be mild.
PMID- 28690315
TI - Targeting nucleolin for better survival in diffuse large B-cell lymphoma.
AB - Anthracyclines have been a cornerstone in the cure of diffuse large B-cell
lymphoma (DLBCL) and other hematological cancers. The ability of anthracyclines
to eliminate DLBCL depends on the presence of topoisomerase-II-alpha (TopIIA), a
DNA repair enzyme complex. We identified nucleolin as a novel binding partner of
TopIIA. Abrogation of nucleolin sensitized DLBCL cells to TopIIA targeting agents
(doxorubicin/etoposide). Silencing nucleolin and challenging DLBCL cells with
doxorubicin enhanced the phosphorylation of H2AX (gammaH2AX-marker of DNA damage)
and allowed DNA fragmentation. Reconstitution of nucleolin expression in
nucleolin-knockdown DLBCL cells prevented TopIIA targeting agent-induced
apoptosis. Nucleolin binding to TopIIA was mapped to RNA-binding domain 3 of
nucleolin, and this interaction was essential for blocking DNA damage and
apoptosis. Nucleolin silencing decreased TopIIA decatenation activity, but
enhanced formation of TopIIA-DNA cleavable complexes in the presence of
etoposide. Moreover, combining nucleolin inhibitors: aptamer AS1411 or nucant N6L
with doxorubicin reduced DLBCL cell survival. These findings are of clinical
importance because low nucleolin levels versus high nucleolin levels in DLBCL
predicted 90-month estimated survival of 70% versus 12% (P<0.0001) of patients
treated with R-CHOP-based therapy.
PMID- 28690318
TI - Haematopoiesis: Osteopontin skews lymphoid-myeloid balance.
PMID- 28690320
TI - Structural biology: Cascade keeps its targets in the loop.
PMID- 28690317
TI - Cytoskeletal control of B cell responses to antigens.
AB - The actin cytoskeleton is essential for cell mechanics and has increasingly been
implicated in the regulation of cell signalling. In B cells, the actin
cytoskeleton is extensively coupled to B cell receptor (BCR) signalling pathways,
and defects of the actin cytoskeleton can either promote or suppress B cell
activation. Recent insights from studies using single-cell imaging and
biophysical techniques suggest that actin orchestrates BCR signalling at the
plasma membrane through effects on protein diffusion and that it regulates
antigen discrimination through the biomechanics of immune synapses. These
mechanical functions also have a role in the adaptation of B cell subsets to
specialized tasks during antibody responses.
PMID- 28690321
TI - Adaptation... that's what you need?
PMID- 28690319
TI - Interbacterial predation as a strategy for DNA acquisition in naturally competent
bacteria.
AB - Natural competence enables bacteria to take up exogenous DNA. The evolutionary
function of natural competence remains controversial, as imported DNA can act as
a source of substrates or can be integrated into the genome. Exogenous homologous
DNA can also be used for genome repair. In this Opinion article, we propose that
predation of non-related neighbouring bacteria coupled with competence regulation
might function as an active strategy for DNA acquisition. Competence-dependent
kin-discriminated killing has been observed in the unrelated bacteria Vibrio
cholerae and Streptococcus pneumoniae. Importantly, both the regulatory networks
and the mode of action of neighbour predation differ between these organisms,
with V. cholerae using a type VI secretion system and S. pneumoniae secreting
bacteriocins. We argue that the forced release of DNA from killed bacteria and
the transfer of non-clonal genetic material have important roles in bacterial
evolution.
PMID- 28690322
TI - Viral infection: Packing to leave.
PMID- 28690323
TI - Mechanisms of sterile inflammation in acetaminophen hepatotoxicity.
PMID- 28690324
TI - Proteasome inhibition suppresses Th17 cell generation and ameliorates autoimmune
development in experimental Sjogren's syndrome.
AB - Immunoproteasome activation in immune cells is involved in the modulation of
immune responses. Increasing evidence indicates that proteasome inhibitors show
beneficial effects in treating autoimmune diseases, but it remains unclear
whether proteasome inhibition is an effective approach for suppressing autoimmune
development in Sjogren's syndrome (SS). Our previous work has demonstrated a
critical role for Th17 cells in the development of experimental SS (ESS) in mice.
In this study, we detected high levels of low-molecular-weight protein 7 (LMP7),
a key subunit of the immunoproteasome, in Th17 cells from ESS mice. Moreover,
treatment with bortezomib (BTZ), a proteasome inhibitor, markedly suppressed Th17
differentiation in both murine and human naive T cells in culture. Furthermore,
ESS mice treated with BTZ displayed significantly higher saliva flow rates and a
reduction in tissue destruction in the salivary glands compared with vehicle
treated ESS mice. Notably, BTZ-treated ESS mice showed markedly decreased Th17
cells, germinal center B cells and plasma cells in the peripheral lymphoid
organs. In addition, adoptively transferred wild type naive CD4+ T cells rapidly
differentiated into Th17 cells and induced salivary dysfunction in IL-17
deficient mice immunized for ESS induction. However, BTZ treatment profoundly
suppressed the donor T-cell-derived Th17 response and ameliorated the reduction
in salivary secretion in IL-17-deficient recipient mice. Taken together, our
findings demonstrate that proteasome inhibition can effectively ameliorate ESS by
suppressing the Th17 response, which may contribute to the development of a novel
therapeutic strategy for the treatment of SS.Cellular &Molecular Immunology
advance online publication, 10 July 2017; doi:10.1038/cmi.2017.8.
PMID- 28690325
TI - Dietary therapy may be sufficient for type 1 diabetes treatment.
PMID- 28690326
TI - SHP-1 (PTPN6) keeps the inflammation at bay: limiting IL-1alpha-mediated
neutrophilic dermatoses by preventing Syk kinase activation.
PMID- 28690327
TI - Long noncoding RNA lncKdm2b: A critical player in the maintenance of group 3
innate lymphoid cells.
PMID- 28690328
TI - IL-33: a jack of all trades in the orchestration of respiratory antibacterial
immunity.
PMID- 28690329
TI - Macrophage's little helper: vitamin A directs alternatively activated monocyte
derived macrophages to tissue-resident macrophages.
PMID- 28690330
TI - IRF1 and BATF-transcription factors that set the epigenetic landscape for Tr1
cell differentiation?
PMID- 28690331
TI - Diet as a strategy for type 1 diabetes prevention.
PMID- 28690334
TI - Particle localization and hyperuniformity of polymer-grafted nanoparticle
materials.
AB - The properties of materials largely reflect the degree and character of the
localization of the molecules comprising them so that the study and
characterization of particle localization has central significance in both
fundamental science and material design. Soft materials are often comprised of
deformable molecules and many of their unique properties derive from the distinct
nature of particle localization. We study localization in a model material
composed of soft particles, hard nanoparticles with grafted layers of polymers,
where the molecular characteristics of the grafted layers allow us to "tune" the
softness of their interactions. Soft particles are particular interesting because
spatial localization can occur such that density fluctuations on large length
scales are suppressed, while the material is disordered at intermediate length
scales; such materials are called "disordered hyperuniform". We use molecular
dynamics simulation to study a liquid composed of polymer-grafted nanoparticles
(GNP), which exhibit a reversible self-assembly into dynamic polymeric GNP
structures below a temperature threshold, suggesting a liquid-gel transition. We
calculate a number of spatial and temporal correlations and we find a significant
suppression of density fluctuations upon cooling at large length scales, making
these materials promising for the practical fabrication of "hyperuniform"
materials.
PMID- 28690333
TI - Characterization and biological significance of IL-23-induced neutrophil
polarization.
AB - Neutrophils are heterogeneous with distinct subsets, and can switch phenotypes to
exert regulatory functions on immunity. We herein demonstrate that IL-23-treated
neutrophils selectively produce IL-17A, IL-17F and IL-22, and display a distinct
gene expression profile in contrast to resting and lipopolysaccharide-treated
neutrophils. IL-17+ neutrophils are present in the colons of mice with dextran
sulfate sodium-induced colitis. Adoptive transfer of IL-23-treated neutrophils
significantly promotes pathogenesis in this model. IL-23 induces neutrophil
polarization through STAT3-dependent RORgammat and BATF pathways. Thus, IL-23
induced neutrophil polarization expresses a unique cytokine-producing profile,
which may contribute to IL-23-mediated inflammatory diseases.
PMID- 28690332
TI - Caspases control antiviral innate immunity.
AB - Caspases are a family of cysteine proteases whose functions have been scrutinized
intensively in recent years. Beyond their established roles in programmed cell
death and inflammatory response, some caspases are also fundamental players in
antiviral immunity by fine-tuning the levels of antiviral signaling adapters and
cytokines, such as type I interferons, which serves as a major, sophisticated
weapon against viruses. Viral infections can result in inflammasome activation
and the initiation of cell death, including apoptosis and pyroptosis, and
multiple caspases are significantly involved in these processes. This review will
focus on the cutting-edge discoveries regarding the multifaceted roles of
caspases in antiviral innate immunity.
PMID- 28690335
TI - Spatially resolved images of reactive ions in the Orion Bar,??.
AB - We report high angular resolution (4.9"*3.0") images of reactive ions SH+, HOC+,
and SO+ toward the Orion Bar photodissociation region (PDR). We used ALMA-ACA to
map several rotational lines at 0.8 mm, complemented with multi-line observations
obtained with the IRAM 30 m telescope. The SH+ and HOC+ emission is restricted to
a narrow layer of 2"- to 10"-width (~800 to 4000 AU depending on the assumed PDR
geometry) that follows the vibrationally excited [Formula: see text] emission.
Both ions efficiently form very close to the H/H2 transition zone, at a depth of
Av?1 mag into the neutral cloud, where abundant C+, S+, and [Formula: see text]
coexist. SO+ peaks slightly deeper into the cloud. The observed ions have low
rotational temperatures (Trot~10-30 K?Tk) and narrow line-widths (~2-3 km s-1), a
factor of ?2 narrower that those of the lighter reactive ion CH+. This is
consistent with the higher reactivity and faster radiative pumping rates of CH+
compared to the heavier ions, which are driven relatively faster toward smaller
velocity dispersion by elastic collisions and toward lower Trot by inelastic
collisions. We estimate column densities and average physical conditions from an
excitation model (n(H2)~105-106 cm-3, n(e-)~10 cm-3, and Tk~200 K). Regardless of
the excitation details, SH+ and HOC+ clearly trace the most exposed layers of the
UV-irradiated molecular cloud surface, whereas SO+ arises from slightly more
shielded layers.
PMID- 28690336
TI - Correlation between X-ray diffraction and Raman spectra of 16 commercial graphene
based materials and their resulting classification.
AB - Structural properties of sixteen (16) commercial samples of graphene-based
materials (GBM) labelled as graphene, graphene oxide or reduced graphene oxide
are investigated at room temperature using X-ray diffraction (XRD) and Raman
spectroscopy. Based on the observed correlation between the results obtained with
these two techniques, these samples are classified into three groups: Group A of
seven samples consisting of graphitic nanosheets with evaluated thickness ?20 nm
and exhibiting both the 2H and 3R phases in XRD; Group B of six samples
exhibiting XRD spectra characteristic of either graphene oxides (GO) or carbons
with some order; and Group C of three samples with XRD spectra characteristic of
disordered carbons. The relative intensities and widths of D, G, D', 2D and (D +
D') bands in the Raman spectra are equally distinguishable between the samples in
groups A, B and C. The width of the D-band is the smallest for Group A samples,
intermediate for group B and the largest for group C samples. The intensity ratio
I(D)/I(G) of the D and G bands in the Raman spectra of the samples is used to
quantify the Raman-active defects whose concentration increases in going from
samples in Group A to those in Group C.
PMID- 28690337
TI - Comparison of Nanoscale Focused Ion Beam and Electrochemical Lithiation in beta
Sn Microspheres.
AB - The development of Li focused ion beams (Li-FIB) enables controlled Li ion
insertion into materials with nanoscale resolution. We take the first step toward
establishing the relevance of the Li-FIB for studies of ion dynamics in
electrochemically active materials by comparing FIB lithiation with conventional
electrochemical lithiation of isolated beta-Sn microspheres. Samples are
characterized by cross-sectioning with Ga FIB and imaging via electron
microscopy. The Li-FIB and electrochemical lithiated Sn exhibit similarities that
suggest that the Li-FIB can be a powerful tool for exploring dynamical Li ion
material interactions at the nanoscale in a range of battery materials.
PMID- 28690338
TI - Continent of pessimism or continent of realism? A multilevel study into the
impact of macro-economic outcomes and political institutions on societal
pessimism, European Union 2006-2012.
AB - The often-posed claim that Europe is a pessimistic continent is not unjustified.
In 2012, 53 percent of European Union (EU) citizens were pessimistic about their
country. Surprisingly, however, societal pessimism has received very little
scientific attention. In this article, we examine to what extent political and
economic factors drive societal pessimism. In terms of political factors, we
expect that supranationalization, political instability, and corruption increase
societal pessimism, as they diminish national political power and can inspire
collective powerlessness. Economically, we expect that the retrenchment of
welfare state provisions and economic decline drive societal pessimism, as these
developments contribute to socioeconomic vulnerability. We assess the impact of
these political and economic factors on the level of societal pessimism in the
EU, both cross-nationally and over time, through multilevel analyses of
Eurobarometer data (13 waves between 2006 and 2012 in 23 EU countries). Our
findings show that the political factors (changes in government, corruption)
primarily explain cross-national differences in societal pessimism, while the
macro-economic context (economic growth, unemployment) primarily explains
longitudinal trends within countries. These findings demonstrate that, to a large
extent, societal pessimism cannot be viewed separately from its political and
economic context.
PMID- 28690339
TI - The tenure gap in electoral participation: instrumental motivation or selection
bias? Comparing homeowners and tenants across four housing regimes.
AB - Integrating housing tenure in Instrumental Motivation Theory predicts a tenure
gap in electoral participation, as homeowners would be more motivated to vote
compared with tenants. The empirical question is whether this effect is causal or
rather due to selection into different housing tenures. This question is tackled
using coarsened exact matching (CEM) on data for 19 countries, allowing us to
better control for endogeneity. Even then, homeowners are found to vote more
often than tenants. This association is stronger in countries characterized by a
strong pro-homeownership ideology and/or where the financialization of housing
markets turned houses into assets.
PMID- 28690340
TI - Run-to-Run Optimization Control Within Exact Inverse Framework for Scan Tracking.
AB - A run-to-run optimization controller uses a reduced set of measurement
parameters, in comparison to more general feedback controllers, to converge to
the best control point for a repetitive process. A new run-to-run optimization
controller is presented for the scanning fiber device used for image acquisition
and display. This controller utilizes very sparse measurements to estimate a
system energy measure and updates the input parameterizations iteratively within
a feedforward with exact-inversion framework. Analysis, simulation, and
experimental investigations on the scanning fiber device demonstrate improved
scan accuracy over previous methods and automatic controller adaptation to
changing operating temperature. A specific application example and quantitative
error analyses are provided of a scanning fiber endoscope that maintains high
image quality continuously across a 20 degrees C temperature rise without
interruption of the 56 Hz video.
PMID- 28690341
TI - Referential Dependencies Between Conflicting Attitudes.
AB - A number of puzzles about propositional attitudes in semantics and philosophy
revolve around apparent referential dependencies between different attitudes
within a single agent's mental state. In a series of papers, Hans Kamp (2003...
2015) offers a general framework for describing such interconnected attitude
complexes, building on DRT and dynamic semantics. I demonstrate that Kamp's
proposal cannot deal with referential dependencies between semantically
conflicting attitudes, such as those in Ninan's (21) puzzle about de re
imagination. To solve the problem I propose to replace Kamp's treatment of
attitudes as context change potentials with a two-dimensional analysis.
PMID- 28690342
TI - ADAPTATION TO POVERTY IN LONG-RUN PANEL DATA.
AB - We consider the link between poverty and subjective well-being and focus in
particular on potential adaptation to poverty. We use panel data on almost 54,000
individuals living in Germany from 1985 to 2012 to show, first, that life
satisfaction falls with both the incidence and intensity of contemporaneous
poverty. We then reveal that there is little evidence of adaptation within a
poverty spell: poverty starts bad and stays bad in terms of subjective well
being. We cannot identify any cause of poverty entry that explains the overall
lack of poverty adaptation.
PMID- 28690343
TI - State-to-state chemistry and rotational excitation of CH+ in photon-dominated
regions.
AB - We present a detailed theoretical study of the rotational excitation of CH+ due
to reactive and nonreactive collisions involving C+(2P), H2, CH+, H and free
electrons. Specifically, the formation of CH+ proceeds through the reaction
between C+(2P) and H2(nuH2 = 1, 2), while the collisional (de)excitation and
destruction of CH+ is due to collisions with hydrogen atoms and free electrons.
State-to-state and initial-state-specific rate coefficients are computed in the
kinetic temperature range 10-3000 K for the inelastic, exchange, abstraction and
dissociative recombination processes using accurate potential energy surfaces and
the best scattering methods. Good agreement, within a factor of 2, is found
between the experimental and theoretical thermal rate coefficients, except for
the reaction of CH+ with H atoms at kinetic temperatures below 50 K. The full set
of collisional and chemical data are then implemented in a radiative transfer
model. Our Non-LTE calculations confirm that the formation pumping due to
vibrationally excited H2 has a substantial effect on the excitation of CH+ in
photon-dominated regions. In addition, we are able to reproduce, within error
bars, the far-infrared observations of CH+ toward the Orion Bar and the planetary
nebula NGC 7027. Our results further suggest that the population of nuH2 = 2
might be significant in the photon-dominated region of NGC 7027.
PMID- 28690344
TI - Searching for blood in Chinese lacquerware: zhu xie hui.
AB - The study gives an overview of the tests and analyses undertaken in the past 20
years to establish the presence of blood in the foundation layers of Chinese
lacquer artefacts and also shows the development of analytical methods over that
period. When undertaking the conservation of lacquer objects it is crucial to
know the type of binding medium as this influences the selection of any
consolidants that may be required in the treatment. Microchemical tests to
identify blood using benzidine and luminol, various chromatographic and mass
spectrometric techniques and DNA analyses were assessed on selected Chinese
lacquer objects, and the results gained are summarized.
PMID- 28690345
TI - N-Heterocyclic Carbene and Chiral Bronsted Acid Cooperative Catalysis for a
Highly Enantioselective [4+2] Annulation.
AB - A chiral NHC/Bronsted acid cooperative catalysis system has been developed for
asymmetric annulation of functionalized benzaldehydes and activated ketones
through dearomative generation of dienolate.
PMID- 28690346
TI - CONTRASTING HABITAT ASSOCIATIONS OF SAGEBRUSH-STEPPE SONGBIRDS IN THE
INTERMOUNTAIN WEST.
AB - Sagebrush (Artemisia spp.) steppe is one of North America's most imperiled
ecosystems, as the result of many factors including grazing, development, fire,
and invasion of exotic plants. Threats to sagebrush steppe are expected to
increase because of climate change and further human development. Many songbirds
use sagebrush steppe opportunistically, but a few obligate species are dependent
on it. To quantify the habitat associations of three sagebrush obligates, the
Sage Thrasher (Oreoscoptes montanus), Sagebrush Sparrow (Artemisiospiza
nevadensis), and Brewer's Sparrow (Spizella breweri), and nine other songbird
species that use this habitat, we surveyed across a broad region of Idaho. At
each of 104 sites, we selected three plots, one each in relatively poor,
moderate, and good condition, defined qualitatively by the cover of native
shrubs. We quantified bird abundance by point counts, described the habitat at
these points by a line-intercept method, and at each plot calculated the fraction
of a circle (radius 1 km) covered in shrubs or grassland. We compared two-scale
occupancy models based on these data by the information-theoretic approach.
According to the models, our qualitative assessment of habitat condition within a
site distinguished birds' use of relatively good habitat from their use of poor
habitats only, not from those in moderate condition. Thus the sagebrush-obligate
species may tolerate some local habitat degradation, at least up to some
unidentified threshold. Occurrence of all three sagebrush obligates correlated
well with one or more characteristics of sagebrush such as its cover, height, or
heterogeneity in height. They differed in the Sage Thrasher being most sensitive
to sagebrush cover, the Sagebrush Sparrow being found more often at lower
elevations, and the Brewer's Sparrow being less sensitive to ground cover. The
nine other species evaluated were less or negatively associated with attributes
of sagebrush. On the basis of these results, we suggest that the three sagebrush
obligates are best conserved by promoting shrublands over a broad range of
elevations, containing both sagebrush and other shrubs in patches of mixed
height, and minimizing invasive annual grasses.
PMID- 28690348
TI - Populations Can Be Essential in Tracking Dynamic Optima.
AB - Real-world optimisation problems are often dynamic. Previously good solutions
must be updated or replaced due to changes in objectives and constraints. It is
often claimed that evolutionary algorithms are particularly suitable for dynamic
optimisation because a large population can contain different solutions that may
be useful in the future. However, rigorous theoretical demonstrations for how
populations in dynamic optimisation can be essential are sparse and restricted to
special cases. This paper provides theoretical explanations of how populations
can be essential in evolutionary dynamic optimisation in a general and natural
setting. We describe a natural class of dynamic optimisation problems where a
sufficiently large population is necessary to keep track of moving optima
reliably. We establish a relationship between the population-size and the
probability that the algorithm loses track of the optimum.
PMID- 28690347
TI - Union Army Veterans, All Grown Up.
AB - This paper overviews the research opportunities made possible by a NIA-funded
program project, Early Indicators, Intergenerational Processes, and Aging. Data
collection began almost three decades ago on 40,000 soldiers from the Union Army
in the US Civil War. The sample contains extensive demographic, economic, and
medical data from childhood to death. In recent years, a large sample of African
American soldiers and an oversampling of soldiers from major US cities have been
added. Hundreds of historical maps containing public health data have been
geocoded to place soldiers and their family members in a geospatial context. With
newly granted funding, thousands of veterans will be linked to the demographic
information available from the census and vital records of their children.
PMID- 28690349
TI - Drinking to Fit in: Examining the Need to Belong as a Moderator of Perceptions of
Best Friends' Alcohol Use and Related Risk Cognitions Among College Students.
AB - The primary objective of the present study was to examine whether the need to
belong moderates the relation between perceived descriptive norms for best friend
alcohol use and alcohol-related cognitions outlined in the Prototype Willingness
model (i.e., willingness, attitudes, and prototype favorability) among college
students. Three hundred forty-six college students (197 female) completed the
survey. Regression results indicated that the effect of perceptions of best
friend alcohol use on risk cognitions was stronger among students reporting a
greater need to belong. The findings suggest that interventions utilizing
descriptive norms may be more efficacious among those higher in a need to belong.
PMID- 28690350
TI - Impartiality, statistical tit-for-tats and the construction of balance: UK
television news reporting of the 2016 EU referendum campaign.
AB - There has been greater news industry recognition in recent years that
impartiality should not be translated into simply balancing the competing sides
of a debate or issue. The binary nature of a referendum campaign represents a
unique moment to consider whether broadcasters have put this into practice beyond
routine political reporting. This study examines how impartiality was editorially
interpreted in television news coverage during the United Kingdom's 2016 European
Union referendum. We carried out a systematic content analysis of the United
Kingdom's main evening bulletins over the 10-week campaign, examining the issues
and sources shaping coverage, as well as all the statistical claims made by
campaign actors. Our aim was to critically examine how notions of impartiality
were constructed and interpreted, exploring any operational limits and political
consequences. Overall, we found that news bulletins maintained a fairly strict
adherence to a central binary balance between issues and actors during the
campaign. But this binary was politically inflected, with a significant imbalance
in party political perspectives, presenting us with a right-wing rather than a
left-wing case for European Union membership. We also found that independent
expert analysis and testimony was sucked into the partisan binary between leave
and remain campaigners, while journalists were reluctant to challenge or
contextualise claims and counter-claims. Journalists were, in this sense,
constrained by the operational definition of impartiality adopted by
broadcasters. We argue for a more evidence-driven approach to impartiality, where
journalists independently explore the veracity of campaign claims and have the
editorial freedom to challenge them. We also suggest that the reliance on claims
and counter-claims by leading Conservative politicians did little to advance
public understanding of the European Union, and helped perpetuate a series of
long-standing negative associations the British media have been reporting for
many decades.
PMID- 28690351
TI - Echo chamber and trench warfare dynamics in online debates.
AB - In this article, we take issue with the claim by Sunstein and others that online
discussion takes place in echo chambers, and suggest that the dynamics of online
debates could be more aptly described by the logic of 'trench warfare', in which
opinions are reinforced through contradiction as well as confirmation. We use a
unique online survey and an experimental approach to investigate and test echo
chamber and trench warfare dynamics in online debates. The results show that
people do indeed claim to discuss with those who hold opposite views from
themselves. Furthermore, our survey experiments suggest that both confirming and
contradicting arguments have similar effects on attitude reinforcement. Together,
this indicates that both echo chamber and trench warfare dynamics - a situation
where attitudes are reinforced through both confirmation and disconfirmation
biases - characterize online debates. However, we also find that two-sided
neutral arguments have weaker effects on reinforcement than one-sided confirming
and contradicting arguments, suggesting that online debates could contribute to
collective learning and qualification of arguments.
PMID- 28690352
TI - Generation of TiII Alkyne Trimerization Catalysts in the Absence of Strong Metal
Reductants.
AB - Low-valent TiII species have typically been synthesized by the reaction of TiIV
halides with strong metal reductants. Herein we report that TiII species can be
generated simply by reacting TiIV imido complexes with 2 equiv of alkyne,
yielding a metallacycle that can reductively eliminate pyrrole while liberating
TiII. In order to probe the generality of this process, TiII-catalyzed alkyne
trimerization reactions were carried out with a diverse range of TiIV
precatalysts.
PMID- 28690353
TI - The Social and Productive Impacts of Zambia's Child Grant.
AB - Accumulated evidence from dozens of cash transfer programs across the world
suggest that there are few interventions that can match the range of impacts and
cost-effectiveness of a small, predictable monetary transfer to poor families in
developing countries. However, individual published impact assessments typically
focus on only one program and one outcome. This article presents two-year impacts
of the Zambian Government's Child Grant, an unconditional cash transfer to
families with children under age five, across a wide range of domains including
consumption, productive activity and women and children's outcomes, making this
one of the first studies to assess both protective and productive impacts of a
national unconditional cash transfer program. We show strong impacts on
consumption, food security, savings and productive activity. However, impacts in
areas such as child nutritional status and schooling depend on initial conditions
of the household, suggesting that cash alone is not enough to solve all
constraints faced by these poor, rural households. Nevertheless, the apparent
transformative effects of this program suggest that unconditional transfers in
very poor settings can contribute to both protection and development outcomes.
PMID- 28690354
TI - A summary of light dose distribution using an IR navigation system for Photofrin
mediated Pleural PDT.
AB - Uniform delivery of light fluence is an important goal for photodynamic therapy.
We present summary results for an infrared (IR) navigation system to deliver
light dose uniformly during intracavitory PDT by tracking the movement of the
light source and providing real-time feedback on the light fluence rate on the
entire cavity surface area. In the current intrapleural PDT protocol, 8 detectors
placed in selected locations in the pleural cavity monitor the light doses. To
improve the delivery of light dose uniformity, an IR camera system is used to
track the motion of the light source as well as the surface contour of the
pleural cavity. A MATLAB-based GUI program is developed to display the light dose
in real-time during PDT to guide the PDT treatment delivery to improve the
uniformity of the light dose. A dualcorrection algorithm is used to improve the
agreement between calculations and in-situ measurements. A comprehensive analysis
of the distribution of light fluence during PDT is presented in both phantom
conditions and in clinical cases.
PMID- 28690355
TI - Evaluation of lung tumor motion management in radiation therapy with dynamic MRI.
AB - Surrogate-based tumor motion estimation and tracing methods are commonly used in
radiotherapy despite the lack of continuous real time 3D tumor and surrogate
data. In this study, we propose a method to simultaneously track the tumor and
external surrogates with dynamic MRI, which allows us to evaluate their
reproducible correlation. Four MRI-compatible fiducials are placed on the
patient's chest and upper abdomen, and multi-slice 2D cine MRIs are acquired to
capture the lung and whole tumor, followed by two-slice 2D cine MRIs to
simultaneously track the tumor and fiducials, all in sagittal orientation. A
phase-binned 4D-MRI is first reconstructed from multi-slice MR images using body
area as a respiratory surrogate and group-wise registration. The 4D-MRI provides
3D template volumes for different breathing phases. 3D tumor position is
calculated by 3D-2D template matching in which 3D tumor templates in 4D-MRI
reconstruction and the 2D cine MRIs from the two-slice tracking dataset are
registered. 3D trajectories of the external surrogates are derived via matching a
3D geometrical model to the fiducial segmentations on the 2D cine MRIs. We tested
our method on five lung cancer patients. Internal target volume from 4D-CT showed
average sensitivity of 86.5% compared to the actual tumor motion for 5 min. 3D
tumor motion correlated with the external surrogate signal, but showed a
noticeable phase mismatch. The 3D tumor trajectory showed significant cycle-to
cycle variation, while the external surrogate was not sensitive enough to capture
such variations. Additionally, there was significant phase mismatch between
surrogate signals obtained from fiducials at different locations.
PMID- 28690356
TI - Diagnostic Index: An open-source tool to classify TMJ OA condyles.
AB - Osteoarthritis (OA) of temporomandibular joints (TMJ) occurs in about 40% of the
patients who present TMJ disorders. Despite its prevalence, OA diagnosis and
treatment remain controversial since there are no clear symptoms of the disease,
especially in early stages. Quantitative tools based on 3D imaging of the TMJ
condyle have the potential to help characterize TMJ OA changes. The goals of the
tools proposed in this study are to ultimately develop robust imaging markers for
diagnosis and assessment of treatment efficacy. This work proposes to identify
differences among asymptomatic controls and different clinical phenotypes of TMJ
OA by means of Statistical Shape Modeling (SSM), obtained via clinical expert
consensus. From three different grouping schemes (with 3, 5 and 7 groups), our
best results reveal that that the majority (74.5%) of the classifications occur
in agreement with the groups assigned by consensus between our clinical experts.
Our findings suggest the existence of different disease-based phenotypic
morphologies in TMJ OA. Our preliminary findings with statistical shape modeling
based biomarkers may provide a quantitative staging of the disease. The
methodology used in this study is included in an open source image analysis
toolbox, to ensure reproducibility and appropriate distribution and dissemination
of the solution proposed.
PMID- 28690357
TI - Federating Heterogeneous Datasets to Enhance Data Sharing and Experiment
Reproducibility.
AB - Recent studies have demonstrated the difficulties to replicate scientific
findings and/or experiments published in past.1 The effects seen in the
replicated experiments were smaller than previously reported. Some of the
explanations for these findings include the complexity of the experimental design
and the pressure on researches to report positive findings. The International
Committee of Medical Journal Editors (ICMJE) suggests that every study considered
for publication must submit a plan to share the de-identified patient data no
later than 6 months after publication. There is a growing demand to enhance the
management of clinical data, facilitate data sharing across institutions and also
to keep track of the data from previous experiments. The ultimate goal is to
assure the reproducibility of experiments in the future. This paper describes
Shiny-tooth, a web based application created to improve clinical data acquisition
during the clinical trial; data federation of such data as well as morphological
data derived from medical images; Currently, this application is being used to
store clinical data from an osteoarthritis (OA) study. This work is submitted to
the SPIE Biomedical Applications in Molecular, Structural, and Functional Imaging
conference.
PMID- 28690358
TI - Characterization of type-II spontaneous parametric down-conversion in domain
engineered PPLN.
AB - We characterize spontaneous parametric downconversion in a domain-engineered,
type-II periodically poled lithium niobate (PPLN) crystal using seeded emission
and single-photon techniques. Using continuous-wave (CW) pumping at 775 nm
wavelength, the signal and idler are at 1532.5 nm and 1567.5 nm, respectively.
The domain-engineered crystal simultaneously phasematches signal and idler pairs:
[H(1532.5 nm), V(1567.5 nm)] and [V(1532.5 nm), H(1567.5 nm)]. We observe the
tuning curves of these processes through difference-frequency generation and
through CW fiber-assisted, single-photon spectroscopy. These measurements
indicate good matching in amplitude and bandwidth of the two processes and that
the crystal can in principle be used effectively to generate polarization
entangled photon pairs.
PMID- 28690359
TI - Mobile Robot and Mobile Manipulator Research Towards ASTM Standards Development.
AB - Performance standards for industrial mobile robots and mobile manipulators (robot
arms onboard mobile robots) have only recently begun development. Low cost and
standardized measurement techniques are needed to characterize system
performance, compare different systems, and to determine if recalibration is
required. This paper discusses work at the National Institute of Standards and
Technology (NIST) and within the ASTM Committee F45 on Driverless Automatic
Guided Industrial Vehicles. This includes standards for both terminology, F45.91,
and for navigation performance test methods, F45.02. The paper defines terms that
are being considered. Additionally, the paper describes navigation test methods
that are near ballot and docking test methods being designed for consideration
within F45.02. This includes the use of low cost artifacts that can provide
alternatives to using relatively expensive measurement systems.
PMID- 28690360
TI - Absorption/Transmission Measurements of PSAP Particle-Laden Filters from the
Biomass Burning Observation Project (BBOP) Field Campaign.
AB - Absorptivity measurements with a laser-heating approach, referred to as the laser
driven thermal reactor (LDTR), were carried out in the infrared and applied at
ambient (laboratory) non-reacting conditions to particle-laden filters from a
three-wavelength (visible) particle/soot absorption photometer (PSAP). The
particles were obtained during the Biomass Burning Observation Project (BBOP)
field campaign. The focus of this study was to determine the particle absorption
coefficient from field-campaign filter samples using the LDTR approach, and
compare results with other commercially available instrumentation (in this case
with the PSAP, which has been compared with numerous other optical techniques).
Advantages of the LDTR approach include 1) direct estimation of material
absorption from temperature measurements (as opposed to resolving the difference
between the measured reflection/scattering and transmission), 2) information on
the filter optical properties, and 3) identification of the filter material
effects on particle absorption (e.g., leading to particle absorption enhancement
or shadowing). For measurements carried out under ambient conditions, the
particle absorptivity is obtained with a thermocouple placed flush with the
filter back surface and the laser probe beam impinging normal to the filter
particle-laden surface. Thus, in principle one can employ a simple experimental
arrangement to measure simultaneously both the transmissivity and absorptivity
(at different discrete wavelengths) and ascertain the particle absorption
coefficient. For this investigation, LDTR measurements were carried out with PSAP
filters (pairs with both blank and exposed filters) from eight different days
during the campaign, having relatively light but different particle loadings. The
observed particles coating the filters were found to be carbonaceous (having
broadband absorption characteristics). The LDTR absorption coefficient compared
well with results from the PSAP. The analysis was also expanded to account for
the filter fiber scattering on particle absorption in assessing particle
absorption enhancement and shadowing effects. The results indicated that
absorption enhancement effects were significant, and diminished with increased
filter particle loading.
PMID- 28690361
TI - Kondo Effect in Magnetic Tunnel Junctions with an AlOx Tunnel Barrier.
AB - The influence of the magnetization configuration on Kondo effect in magnetic
tunnel junction is investigated. In the parallel configuration, an additional
resistance contribution (R*) below 40 K exhibits a logarithmic temperature
dependence, indicating the presence of Kondo effect. However, in the anti
parallel configuration, the Kondo-effect-associated spin-flip scattering has a
nontrivial contribution to the tunneling current, which compensates the reduction
of the current directly caused by Kondo scattering, making R* disappear. These
results indicate that suppression and restoration of Kondo effect can be
experimentally achieved by altering the magnetization configuration, enhancing
our understanding of the role of Kondo effect in spin-dependent transport.
PMID- 28690362
TI - Complementing, competing, or co-operating? Exploring newspapers' portrayals of
the European Parliament and national parliaments in EU affairs.
AB - The paper explores newspapers' portrayals of the European Parliament and national
parliaments (NPs) in European Union (EU) affairs. To understand underlying
perceptions of journalists, it takes public parliamentary activities and looks at
their influence on parliaments' news visibility in Finland, Germany and the UK in
routine periods in 2011 and 2012. This is done against the background that
parliaments, regarded as ultimate legitimisers of state power, depend on the mass
media to reach their citizenry. However, journalists follow their own agenda in
publishing parliamentary news. In this regard, they may highlight the
complementarity, competition or cooperation of parliaments in the EU's unique
multi-tier environment. Overall, our results suggest that NPs correspond stronger
with newsmakers' anticipation of readership interest. In addition, findings seem
to support the assumption that parliaments in the EU are mostly perceived as
complementary, separate legislative branches in EU decision-making.
PMID- 28690363
TI - INTEGRATING DATA ANALYTICS AND SIMULATION METHODS TO SUPPORT MANUFACTURING
DECISION MAKING.
AB - Modern manufacturing systems are installed with smart devices such as sensors
that monitor system performance and collect data to manage uncertainties in their
operations. However, multiple parameters and variables affect system performance,
making it impossible for a human to make informed decisions without systematic
methodologies and tools. Further, the large volume and variety of streaming data
collected is beyond simulation analysis alone. Simulation models are run with
well-prepared data. Novel approaches, combining different methods, are needed to
use this data for making guided decisions. This paper proposes a methodology
whereby parameters that most affect system performance are extracted from the
data using data analytics methods. These parameters are used to develop scenarios
for simulation inputs; system optimizations are performed on simulation data
outputs. A case study of a machine shop demonstrates the proposed methodology.
This paper also reviews candidate standards for data collection, simulation, and
systems interfaces.
PMID- 28690364
TI - Schooling and Labor Market Effects of Temporary Authorization: Evidence from
DACA.
AB - This paper explores the labor market and schooling effects of the Deferred Action
for Childhood Arrivals (DACA) initiative, which provides work authorization to
eligible immigrants along with a temporary reprieve from deportation. The
analysis relies on a difference-in-differences approach that exploits the
discontinuity in program rules to compare eligible individuals to ineligible,
likely undocumented immigrants before and after the program went into effect. To
address potential endogeneity concerns, we focus on youths that likely met DACA's
schooling requirement when the program was announced. We find that DACA reduced
the probability of school enrollment of eligible higher-educated individuals, as
well as some evidence that it increased the employment likelihood of men, in
particular. Together, these findings suggest that a lack of authorization may
lead individuals to enroll in school when working is not a viable option. Thus,
once employment restrictions are relaxed and the opportunity costs of higher
education rise, eligible individuals may reduce investments in schooling.
PMID- 28690365
TI - Relative Equilibria in the Spherical, Finite Density Three-Body Problem.
AB - The relative equilibria for the spherical, finite density three-body problem are
identified. Specifically, there are 28 distinct relative equilibria in this
problem which include the classical five relative equilibria for the point-mass
three-body problem. None of the identified relative equilibria exist or are
stable over all values of angular momentum. The stability and bifurcation
pathways of these relative equilibria are mapped out as the angular momentum of
the system is increased. This is done under the assumption that they have equal
and constant densities and that the entire system rotates about its maximum
moment of inertia. The transition to finite density greatly increases the number
of relative equilibria in the three-body problem and ensures that minimum energy
configurations exist for all values of angular momentum.
PMID- 28690366
TI - Multipole Vortex Blobs (MVB): Symplectic Geometry and Dynamics.
AB - Vortex blob methods are typically characterized by a regularization length scale,
below which the dynamics are trivial for isolated blobs. In this article, we
observe that the dynamics need not be trivial if one is willing to consider
distributional derivatives of Dirac delta functionals as valid vorticity
distributions. More specifically, a new singular vortex theory is presented for
regularized Euler fluid equations of ideal incompressible flow in the plane. We
determine the conditions under which such regularized Euler fluid equations may
admit vorticity singularities which are stronger than delta functions, e.g.,
derivatives of delta functions. We also describe the symplectic geometry
associated with these augmented vortex structures, and we characterize the
dynamics as Hamiltonian. Applications to the design of numerical methods similar
to vortex blob methods are also discussed. Such findings illuminate the rich
dynamics which occur below the regularization length scale and enlighten our
perspective on the potential for regularized fluid models to capture multiscale
phenomena.
PMID- 28690367
TI - Solution of the Kirchhoff-Plateau Problem.
AB - The Kirchhoff-Plateau problem concerns the equilibrium shapes of a system in
which a flexible filament in the form of a closed loop is spanned by a liquid
film, with the filament being modeled as a Kirchhoff rod and the action of the
spanning surface being solely due to surface tension. We establish the existence
of an equilibrium shape that minimizes the total energy of the system under the
physical constraint of noninterpenetration of matter, but allowing for points on
the surface of the bounding loop to come into contact. In our treatment, the
bounding loop retains a finite cross-sectional thickness and a nonvanishing
volume, while the liquid film is represented by a set with finite two-dimensional
Hausdorff measure. Moreover, the region where the liquid film touches the surface
of the bounding loop is not prescribed a priori. Our mathematical results
substantiate the physical relevance of the chosen model. Indeed, no matter how
strong is the competition between surface tension and the elastic response of the
filament, the system is always able to adjust to achieve a configuration that
complies with the physical constraints encountered in experiments.
PMID- 28690368
TI - On the impact of model selection on predictor identification and parameter
inference.
AB - We assessed the ability of several penalized regression methods for linear and
logistic models to identify outcome-associated predictors and the impact of
predictor selection on parameter inference for practical sample sizes. We studied
effect estimates obtained directly from penalized methods (Algorithm 1), or by
refitting selected predictors with standard regression (Algorithm 2). For linear
models, penalized linear regression, elastic net, smoothly clipped absolute
deviation (SCAD), least angle regression and LASSO had a low false negative (FN)
predictor selection rates but false positive (FP) rates above 20 % for all sample
and effect sizes. Partial least squares regression had few FPs but many FNs. Only
relaxo had low FP and FN rates. For logistic models, LASSO and penalized logistic
regression had many FPs and few FNs for all sample and effect sizes. SCAD and
adaptive logistic regression had low or moderate FP rates but many FNs. 95 %
confidence interval coverage of predictors with null effects was approximately
100 % for Algorithm 1 for all methods, and 95 % for Algorithm 2 for large sample
and effect sizes. Coverage was low only for penalized partial least squares
(linear regression). For outcome-associated predictors, coverage was close to 95
% for Algorithm 2 for large sample and effect sizes for all methods except
penalized partial least squares and penalized logistic regression. Coverage was
sub-nominal for Algorithm 1. In conclusion, many methods performed comparably,
and while Algorithm 2 is preferred to Algorithm 1 for estimation, it yields valid
inference only for large effect and sample sizes.
PMID- 28690369
TI - Psychotherapy in historical perspective.
AB - This article will briefly explore some of the ways in which the past has been
used as a means to talk about psychotherapy as a practice and as a profession,
its impact on individuals and society, and the ethical debates at stake. It will
show how, despite the multiple and competing claims about psychotherapy's history
and its meanings, historians themselves have, to a large degree, not attended to
the intellectual and cultural development of many therapeutic approaches. This
absence has the potential consequence of implying that therapies have emerged as
value-free techniques, outside of a social, economic and political context. The
relative neglect of psychotherapy, by contrast with the attention historians have
paid to other professions, particularly psychiatry, has also underplayed its
societal impact. This article will foreground some of the instances where
psychotherapy has become an object of emerging historical interest, including the
new research that forms the substance of this special issue of History of the
Human Sciences.
PMID- 28690370
TI - Unbiased Bayesian inference for population Markov jump processes via random
truncations.
AB - We consider continuous time Markovian processes where populations of individual
agents interact stochastically according to kinetic rules. Despite the increasing
prominence of such models in fields ranging from biology to smart cities,
Bayesian inference for such systems remains challenging, as these are continuous
time, discrete state systems with potentially infinite state-space. Here we
propose a novel efficient algorithm for joint state/parameter posterior sampling
in population Markov Jump processes. We introduce a class of pseudo-marginal
sampling algorithms based on a random truncation method which enables a
principled treatment of infinite state spaces. Extensive evaluation on a number
of benchmark models shows that this approach achieves considerable savings
compared to state of the art methods, retaining accuracy and fast convergence. We
also present results on a synthetic biology data set showing the potential for
practical usefulness of our work.
PMID- 28690371
TI - How to Overcome the World: Henry, Heidegger, and the Post-Secular.
AB - If there is such a 'post-secular' milieu, mindset, or thesis, it will need to
furnish its own interpretation of the 'world' in ways distinct from those
championed by the secular. Indeed an essential aspect of the 'secular' is how it
has interpreted the 'world' (kosmos) as the 'space, time, and age' (Latin
saecularis) in which things come into presence clearly, neutrally, and obviously.
This paper interprets and compares some of Heidegger's (especially the Heraclitus
Seminars) and Henry's (especially 'Phenomenology of Life') specific engagements
with the theme of 'world', and how each thinker claims the world itself is
presentable as a phenomenon, namely, via disclosive moods and the self-revelation
of life. Since the world can appear, and its phenomenality can be presented, an
inquiry into the specific, inconspicuous means by which the experiences of the
world's neutrality, clarity, and obviousness might yield phenomenological
description. What presents itself as neutral is precisely what demands attention
by merit of its hiddenness.
PMID- 28690372
TI - On Seizing the Source: Toward a Phenomenology of Religious Violence.
AB - In this paper I argue that we need to analyze 'religious violence' in the 'post
secular context' in a twofold way: rather than simply viewing it in terms of mere
irrationality, senselessness, atavism, or monstrosity - terms which, as we
witness today on an immense scale, are strongly endorsed by the contemporary
theater of cruelty committed in the name of religion - we also need to understand
it in terms of an 'originary supplement' of 'disengaged reason'. In order to
confront its specificity beyond traditional explanations of violence, I propose
an integrated phenomenological account of religion that traces the phenomenality
of religion in terms of a correlation between the originary givenness of
transcendence and capable man's creative capacities to respond to it. Following
Ricoeur, I discuss 'religious violence' in terms of a monopolizing appropriation
of the originary source of givenness that conflates man's freedom to poetically
respond to the appeal of the foundational with the surreptitiously claimed
sovereignty to make it happen in a practical transfiguration of the everyday.
PMID- 28690373
TI - FEMINIST TO POSTFEMINIST: contemporary biofictions by and about women artists.
AB - Biographical novels about historical women artists have been experiencing a
veritable boom in recent years. Written mostly by women, they can be understood
as women authors' attempts to reach out across time (and often, space) to other
"artistic" women whose lives "speak to us" today. It has long been a key insight
of historical fiction research that a historical novel reveals more about the
time in which it was written than the time in which it is set. As such, it can be
assumed that contemporary novels about historical women speak as much to twenty
first-century conceptions of femininity as to particular historical moments of
female subjectivity. This paper will compare two novels about historical women
artists: Janice Galloway's Clara (2002) about nineteenth-century German pianist
Clara Wieck-Schumann and Priya Parmar's Exit the Actress (2011) about Restoration
actress Nell Gwyn. While based on historical facts, both these novels use the
greater freedom of fiction to depart from biographical conventions. It will be
demonstrated that although they resemble each other on the discourse level,
employing shifts in the narrative perspective, conspicuous typography, and
graphic elements, they differ markedly in the biographical and fictional
subgenres in which they participate and, hence, in their gender politics.
PMID- 28690374
TI - The energy divide: Integrating energy transitions, regional inequalities and
poverty trends in the European Union.
AB - Energy poverty can be understood as the inability of a household to secure a
socially and materially necessitated level of energy services in the home. While
the condition is widespread across Europe, its spatial and social distribution is
highly uneven. In this paper, the existence of a geographical energy poverty
divide in the European Union (EU) provides a starting point for conceptualizing
and exploring the relationship between energy transitions - commonly described as
wide-ranging processes of socio-technical change - and existing patterns of
regional economic inequality. We have undertaken a comprehensive analysis of
spatial and temporal trends in the national-scale patterns of energy poverty, as
well as gas and electricity prices. The results of our work indicate that the
classic economic development distinction between the core and periphery also
holds true in the case of energy poverty, as the incidence of this phenomenon is
significantly higher in Southern and Eastern European EU Member States. The paper
thus aims to provide the building blocks for a novel theoretical integration of
questions of path-dependency, uneven development and material deprivation in
existing interpretations of energy transitions.
PMID- 28690376
TI - Linear epitope prediction in HPV type 16 E7 antigen and their docked interaction
with human TMEM 50A structural model.
AB - Human Papilloma Virus (HPV) HPV type 16 E7 antigen is a known target in cervical
cancer. We report the predicted potential epitopes in the E7 antigen. We further
describe the subsequent interaction of these linear epitope peptides with the
human TMEM 50 A structural model using molecular docking. This data finds
application in the development of components towards HPV associated disease
prevention.
PMID- 28690377
TI - Dengue Symptoms Significance in Anti-Dengue Drug Development: Road Less
Travelled.
AB - : Dengue outbreak has affected rural areas of Delhi-NCR, Haryana widely but it
lacks in surveillance. High cases of dengue symptoms were reported in these
regions whereas dengue symptoms have been a neglected issue in the anti-dengue
drug development. Therefore, this study aims to analyze the status of the dengue
infection, a rural issue of Delhi-NCR, Haryana and to identify the significance
of dengue symptoms in anti-dengue drug development. The study was conducted when
there is high chance of dengue infection i.e. from August 2015 to October 2015 at
OPD Unit of PR Institute of Medical Science & Research, Delhi-NCR, Sonepat. It
includes 158 patients from 24 rural areas of Haryana comprising both males and
females from different age groups. Out of 20% cases, 6% were IgG-Positive, 9%
were IgMPositive and 88% were NS1-Positive and rest 80% was normal. It includes
44% cases of thrombocytopenia. Badkhalsa village (28%), age group 18-24 (34%) and
males (63%) reported cases of high infection. It was found that people with fewer
platelet counts (Rai village) were not suffering from dengue whereas people with
more platelet count reported dengue infection (Badkhalsa village). INTERPRETATION
& CONCLUSION: This study focuses on new research directions by highlighting the
dengue symptoms importance in anti-dengue drug development also it is a first
attempt to investigate the status of dengue, a rural issue of Delhi-NCR, Haryana
and suggests that health authorities and people living in these regions should
take initiatives for better health.
PMID- 28690378
TI - Molecular docking analysis of nitisinone with homogentisate 1,2 dioxygenase.
AB - Alkaptonuria is an inherited disease that is caused by homogenticate
accumulation. Deficiency or mutation in Homogentisate 1,2 dioxygenase gene
(chromosome 3q21-q23) leads to production of incorrectly folded or truncated
enzyme. Several studies indicated that competitive inhibitors of Homogentisate
1,2 dioxygenase like Nitisinone could be used for Alkaptonuria treatment.
Therefore, it is of interest to design better inhibitors of the enzyme. We used
subset 3_p.0.5 from Zinc database as the virtual screening library by PyRx
software relaying on Lamarckian genetics algorithm. Top 10 hits with more
efficient binding affinity were analyzed and hit No#5 and No# 7 was selected for
further design. In Lig No#5, we decreased the hydrophobicity by adding oxygen in
the hydrophobic tail of the molecule at positions C5 and C10. The new compound of
(2Z, 5Z, 8Z)-6,9-Dihydroxy-2-(2-hydroxy-5-oxo-1,3-cyclohexadien-1-yl)-2,5,8
decatrienoic acid satisfied Lipinski rules as well as PhysChem and FafDrugs
filters. Moreover, the modified version of Lig No# 7 with the IUPAC name of [2
(Carboxymethyl)-3,5-dihydroxyphenyl] acetic acid satisfies the Lipisnki, FafDrugs
and Physchem.
PMID- 28690379
TI - Competitive rational inhibitor design to 4-maleylaceto-acetate isomerase.
AB - Tyrosinemia type I is the result of genetic disorder in fomaryl acetoacetase gene
that leads to 4-fumaryl acetoacetate accumulation. The current treatment for
tyrosinemia type I is nitisinone that inhibits 4-hydroxyphenyl pyruvic
dioxygenase in competitive manner. In the present study, we have designed two
theoretical chemicals, which could inhibit the direct enzyme responsible for
fumarylacetoacetate formation. Subset 2_p.0.5 from Zinc database was screened by
PyRx software using a Lamarckian genetic algorithm as the scoring function for
docking. Top nine successive hits were selected for further pharmacological
analysis and finally the new designed ligands RD6-2 (3Z)- 1,3-Butadiene-1,1,2,4
tetrol and RD-7-1 ((Z)-3-[4-Hydroxy-1-(hydroxymethyl)cyclohexyl]-2-propene-1,2
diol could pass PhysChem, FAFDrugs and AdmetSAR filter. The designed ligands were
non-substrate and non-inhibitor of CYP450 and nontoxic in AMES test. LD50 of RD-6
2 was 793mg/kg with the toxicity class of four and The LD50 of RD-7-1 was
calculated as 5000mg/kg within the toxicity class of five. The designed molecules
are introduced as the new theoretical small molecules, which can theoretically
inhibit 4- maleylacetoacetate isomerase in a competitive manner.
PMID- 28690375
TI - Arousal and the control of perception and movement.
AB - Recent discoveries on the nature of the activity generated by the reticular
activating system (RAS) suggest that arousal is much more involved in perception
and movement than previously thought. The RAS is not simply an amorphous,
unspecific region but rather a distinct group of nuclei with specific cell and
transmitter types that control waking and modulate such processes as perception
and movement. Thus, disturbances in the RAS will affect a number of neurological
disorders. The discovery of gamma band activity in the RAS determined that high
threshold calcium channels are responsible for generating gamma band activity in
the RAS. Results showing that waking is mediated by CaMKII modulation of P/Q-type
channels and REM sleep is modulated by cAMP/PK modulation of N-type channels
points to different intracellular pathways influencing each state. Few studies
address these important breakthroughs. Novel findings also show that the same
primate RAS neurons exhibiting activity in relation to arousal are also involved
in locomotion. Moreover, deep brain stimulation of this region, specifically the
pedunculopontine nucleus (PPN DBS), in Parkinson's disease has salutary effects
on movement, sleep, and cognition. Gamma oscillations appear to participate in
sensory perception, problem solving, and memory, and coherence at these
frequencies may occur at cortical or thalamocortical levels. However, rather than
participating in the temporal binding of sensory events, gamma band activity
generated in the RAS may help stabilize coherence related to arousal, providing a
stable activation state during waking, and relay such activation to the cortex.
Continuous sensory input will thus induce gamma band activity in the RAS to
participate in the processes of preconscious awareness, and provide the essential
stream of information for the formulation of many of our perceptions and actions.
Such a role has received little attention but promises to help understand and
treat a number of neurological disorders.
PMID- 28690380
TI - Identification of inhibitors against alpha-Isopropylmalate Synthase of
Mycobacterium tuberculosis using docking-MM/PBSA hybrid approach.
AB - alpha-Isopropylmalate Synthase (alpha-IPMS) encoded by leuA in Mycobacterium
tuberculosis (M.tb) is involved in the leucine biosynthesis pathway and is
extremely critical for the synthesis of branched-chain amino acids (leucine,
isoleucine and valine). alpha-IPMS activity is required not only for the
proliferation of M.tb but is also indispensable for its survival during the
latent phase of infection. It is absent in humans and is widely regarded as one
of the validated drug targets against Tuberculosis (TB). Despite its
essentiality, any study on designing of potential chemical inhibitors against
alpha-IPMS has not been reported so far. In the present study, in silico
identification of putative inhibitors against alpha-IPMS exploring three chemical
databases i.e. NCI, DrugBank and ChEMBL is reported through structurebased drug
design and filtering of ligands based on the pharmacophore feature of the
actives. In the absence of experimental results of any inhibitor against alpha
IPMS, a stringent validation of docking results is done by comparing with
molecular mechanics/Poisson- Boltzmann surface area (MM/PBSA) calculations by
investigating two more proteins for which experimental results are known.
PMID- 28690381
TI - Polymorphism of the PAI-1gene (4G/5G) may be linked with Polycystic Ovary
Syndrome and associated pregnancy disorders in South Indian Women.
AB - Polycystic Ovary syndrome (PCOS) is the most common endocrine disorder affecting
5 - 10% of all women of reproductive age group. The present research was carried
out to study the impact of Plasminogen Activator Inhibitor (PAI-1) 4G/5G
polymorphism (rs1799889) in PCOS, and the risk of developing PCOS in South Indian
Population. The study was carried out in 60 subjects of South Indian population
(30 PCOS and 30 Non PCOS) recruited from ARC Research and Fertility Centre,
Chennai, India. Genotype and Allelic frequencies were compared by Fisher exact
test, Hardy Weinberg equilibrium. p<0.05 was considered statistically
significant. The Genotype frequency difference between PCOS and non-PCOS was
observed as statistically non-significant (p=0.4647, OR=1.3077, 95% CI 0.63
2.68). The allelic frequency distribution in Spontaneous Abortion (SAB) cases in
total subjects is not found to be statistically significant (p=0. 29), however
the PCOS women carrying mutant homozygous and heterozygous genotype are more
prone to recurrent pregnancy loss. Out of 17 Implantation failure cases, 23.52%
were found to carry mutant homozygous (4G/4G), and 66.66% carried mutant
heterozygous (4G/5G), and 5.88% carried wild type homozygous (5G/5G), the allelic
difference was highly significant with 4G (62.5%), and 5G (37.5%). P value is
highly significant and recorded at p=0.0164. The positive correlation between PAI
1 4G/5G polymorphism and PCOS risk was not observed in this study, however, the
correlation between Recurrent Pregnancy Loss (RPL) and Implantation failures were
observed in PCOS cases.
PMID- 28690382
TI - QSAR based predictive modeling for anti-malarial molecules.
AB - Malaria is a predominant infectious disease, with a global footprint, but
especially severe in developing countries in the African subcontinent. In recent
years, drug-resistant malaria has become an alarming factor, and hence the
requirement of new and improved drugs is more crucial than ever before. One of
the promising locations for antimalarial drug target is the apicoplast, as this
organelle does not occur in humans. The apicoplast is associated with many unique
and essential pathways in many Apicomplexan pathogens, including Plasmodium. The
use of machine learning methods is now commonly available through open source
programs. In the present work, we describe a standard protocol to develop
molecular descriptor based predictive models (QSAR models), which can be further
utilized for the screening of large chemical libraries. This protocol is used to
build models using training data sourced from apicoplast specific bioassays.
Multiple model building methods are used including Generalized Linear Models
(GLM), Random Forest (RF), C5.0 implementation of a decision tree, Support Vector
Machines (SVM), K-Nearest Neighbour and Naive Bayes. Methods to evaluate the
accuracy of the model building method are included in the protocol. For the given
dataset, the C5.0, SVM and RF perform better than other methods, with comparable
accuracy over the test data.
PMID- 28690383
TI - Molecular docking based screening of Listeriolysin-O for improved inhibitors.
AB - Listeriolysine-O (LLO) is a 50KDa protein responsible for Listeria monocytogenes
pathogenicity. The structure of LLO (PDB ID: 4CDB) with domains D1 to D4 is
known. Therefore, it is of interest to identify conserved regions among LLO
variants for destabilizing oligomerization (50 mer complex) of its monomers using
appropriate inhibitors. Therefore, it is of interest to identify suitable
inhibitors for inhibiting LLO. Previous reports suggest the use of flavanoids
like compounds for inhibiting LLO. Our interest is to identify improved compounds
to destabilize LLO oligomerization. We used a library (Zinc database) containing
200,000 drug-like compounds against LLO using molecular docking based screening.
This resulted in five hits that were further analyzed for pharmacological
properties. The hit #1 (2-methyloctadecane- 1, 3, 4-triol) was further refined
using appropriate modifications for creating a suitable pharmacophore model LLO
inhibition. The modified compound (1-(4-Cyclopent-3-enyl-6, 7-dihydroxy-8
hydroxymethyl-nona-2, 8-dienylideneamino)-penta-1,4-dien-3-one) shows fitting
binding properties with LLO with no undesirable pharmacological properties such
as toxicity.
PMID- 28690384
TI - Continuity conditions for Q-Bezier curves of degree n.
AB - As a new method of representing curves, Q-Bezier curves not only exhibit the
beneficial properties of Bezier curves but also allow effective shape adjustment
by changing multiple shape parameters. In order to resolve the problem of not
being able to construct complex curves using a single curve, we study the
geometric continuity conditions for Q-Bezier curves of degree n. Following the
analysis of basis functions and terminal properties of Q-Bezier curves of degree
n, the continuity conditions of [Formula: see text] and [Formula: see text]
between two adjacent Q-Bezier curves are proposed. In addition, we discuss the
specific steps of smooth continuity for Q-Bezier curves and analyze the influence
rules of shape parameters for Q-Bezier curves. The modeling examples show that
the proposed method is effective and easy to achieve, making it useful for
constructing complex curves for engineering design.
PMID- 28690385
TI - The Use of Religious Coping Methods in a Secular Society: A Survey Study Among
Cancer Patients in Sweden.
AB - In the present article, based on results from a survey study in Sweden among
2,355 cancer patients, the role of religion in coping is discussed. The survey
study, in turn, was based on earlier findings from a qualitative study of cancer
patients in Sweden. The purpose of the present survey study was to determine to
what extent results obtained in the qualitative study can be applied to a wider
population of cancer patients in Sweden. The present study shows that use of
religious coping methods is infrequent among cancer patients in Sweden. Besides
the two methods that are ranked in 12th and 13th place, that is, in the middle
(Listening to religious music and Praying to God to make things better), the
other religious coping methods receive the lowest rankings, showing how
nonsignificant such methods are in coping with cancer in Sweden. However, the
question of who turns to God and who is self-reliant in a critical situation is
too complicated to be resolved solely in terms of the strength of individuals'
religious commitments. In addition to background and situational factors, the
culture in which the individual was socialized is an important factor. Regarding
the influence of background variables, the present results show that gender, age,
and area of upbringing played an important role in almost all of the religious
coping methods our respondents used. In general, people in the oldest age-group,
women, and people raised in places with 20,000 or fewer residents had a higher
average use of religious coping methods than did younger people, men, and those
raised in larger towns.
PMID- 28690387
TI - EDITORIAL.
PMID- 28690386
TI - Sexuality Education Intervention for Parents of Children with Disabilities: A
Pilot Training Program.
AB - The purpose of the study is to evaluate pilot sexuality education intervention
for parents of children with disabilities between ages of 6 and 25 years old. A
within subjects design was utilized and 15 parents of children with disabilities
were recruited to receive a two-week sexuality education without a control group.
A paired-samples t-test results showed that there was a significant difference
between the participants' pre-test and post intervention scores in their:
attitude and beliefs, sexual communication, knowledge, and self-efficacy of
sexuality education among children with disabilities (all p<.001). The
intervention change the participants sexual communication behavior and increased
knowledge about sexuality education with children with disabilities.
PMID- 28690388
TI - 23Na MRI and myometry to compare eplerenone vs. glucocorticoid treatment in
Duchenne dystrophy.
AB - In this pilot study we tested whether a low dose application of a mild diuretic
substance such as eplerenone is beneficial in early stages of Duchenne muscular
dystrophy using 23Na und 1H imaging, myometry, and clinical testing versus the
glucocorticoid gold standard. Two 7-years old patients with DMD were examined on
a 3T MRI system. 1H MRI and 23Na density-adapted 3-dimensional radial MRI
sequences were performed both before and 1, 3 and 6 months after therapy with
eplerenone respectively cortisone. We quantified fatty infiltration on T1
weighted images using subcutaneous fat as reference and fat fraction with a two
point DIXON sequence. Muscle oedema was quantified on STIR images and DIXON water
maps with background noise as reference. We quantified Na+ by a muscular tissue
concentration sequence with a 51.3mM Na+ with 5% agarose reference tube. A Na+ IR
sequence was used for determination of mainly myoplasmic Na+. Correspondingly
myometry of muscles and tendons were assessed. Clinical tests (i.e. 4-steps-test)
and blood counts (i.e. K+) were done by a pediatrician. Under eplerenone therapy
we detected a reduction of muscular oedema, intracellular-weighted sodium IR
signal and muscular sodium concentration. The oedema reduction in the DMD patient
receiving eplerenone was more pronounced to the patient with cortisone. Myometric
measured tissue parameters such as muscle stiffness had a more pronounced effect
in the child treated with eplerenone after a first increase in muscle stiffness
both after eplerenone and cortisone treatment. Clinical abilities during both
therapies were mostly constant. Eplerenone might be a possible new therapy option
in DMD patients.
PMID- 28690389
TI - Personality traits in patients with myotonic dystrophy type 2.
AB - Myotonic dystrophy type 2 (DM2) is a multisystem disorder that affects many
organs and systems, including the brain. The objective is to analyze personality
patterns in myotonic dystrophy type 2 (DM2) compared to DM1 control group. The
study comprised 27 consecutive genetically confirmed DM2 patients and control
group of 44 DM1 patients. Personality traits were assessed with the Millon
Multiaxial Clinical Inventory III (MMCI III). In DM2 group there were no scale
with pathological scores, although compulsive and paranoid traits were the most
prominent. DM2 patients had lower scores compared to DM1 patients in almost all
scales. Pathological scores on clinical symptom scales were not observed,
although anxiety scale almost approached this value. Patients with higher
compulsive score had higher level of education (rho = +0.53, p < 0.01). On the
other hand, higher paranoid score correlated with younger age at onset (rho =
0.34, p < 0.01) and lower educational level (rho = -0.26, p < 0.05). Our results
did not show significant personality impairments in patients with DM2. However,
following personality traits were predominant: compulsive (in patients with
higher education) and paranoid (in patients with lower education and earlier age
at onset). The most common clinical symptoms were anxiety and somatization.
PMID- 28690391
TI - Mitochondrial ANT-1 related adPEO leading to cognitive impairment: is there a
link?
AB - ANT1 is one of the nuclear genes responsible of autosomal dominant progressive
external ophthalmoplegia (adPEO) with mitochondrial DNA multiple deletions. The
course of ANT1- related adPEO is relatively benign, symptoms being generally
restricted to skeletal muscle. Here we report the case of an Italian 74 years old
woman with ANT1-related adPEO and dementia. Further studies are needed to assess
the prevalence of central neurological manifestations in ANT1 mitochondrial
disease.
PMID- 28690390
TI - Integrated care of muscular dystrophies in Italy. Part 1. Pharmacological
treatment and rehabilitative interventions.
AB - This paper describes the pharmacological therapies and rehabilitative
interventions received by 502 patients with Muscular Dystrophies, evaluated in
relation to patient's socio-demographic and clinical variables, and geographical
areas. Data were collected by the MD-Socio-Demographic and Clinical Schedule (MD
SC-CS) and by the Family Problems Questionnaire (FPQ). The most part of the
enrolled patients were in drug treatment. The number of the medications increased
in relation to patient's age, disability degree and duration of illness and was
higher among patients with Duchenne Muscular Dystrophy (DMD) compared with Becker
(BMD) or Limb-Girdle Muscular Dystrophies (LGMD). Steroids (deflazacort or
prednisone) were the drug most frequently used, followed by cardiologic and bone
metabolism drugs. In general, patients using steroids were younger and had a
shorter duration of illness; patients using cardiac drugs and dietary supplements
were older and had a longer duration of illness. Rehabilitative interventions
were provided to about 70% (351/502) of patients, mainly DMD. Of these,
physiotherapy was the more frequent treatment (96.6%) and was prevalently
performed in rehabilitative centres (about 70% of patients) and at home in only
30%. Hydrokinetic-therapy was practiced by 6.8% of patients. Respiratory
rehabilitation was provided to 47.0% of patients (165/351) and assisted
mechanical ventilaventilation to 13.1% (46). The amount of rehabilitative
interventions increased in relation to the patient's age, level of disability and
duration of illness. Compared to Central and Northern Italy, in Southern Italy
there was a higher attention to cardiological impairment as shown by a higher
number of patients receiving heart drugs. No statistically significant
differences concerning the possibility to have access to rehabilitative
interventions were noted among the three geographical areas. However, patient
living in Southern Italy tend to receive rehabilitation more often at home.
PMID- 28690392
TI - Congenital myasthenic syndrome: phenotypic variability in patients harbouring
p.T159P mutation in CHRNE gene.
AB - Congenital myasthenic syndromes (CMS) are rare and heterogeneous genetic diseases
characterized by compromised neuromuscular transmission and clinical features of
fatigable weakness; age at onset, presenting symptoms, distribution of weakness,
and response to treatment differ depending on the underlying molecular defect.
Mutations in one of the multiple genes, encoding proteins expressed at the
neuromuscular junction, are currently known to be associated with subtypes of
CMS. The most common CMS syndrome identified is associated with mutation in the
CHRNE gene, causing principally muscle nicotinic acetylcholine receptor
deficiency, that results in reduced receptor density on the postsynaptic
membrane. We describe the clinical, neurophysiological and molecular features of
two unrelated CMS Italian families with marked phenotypic variability, carrying
the already reported p.T159P mutation in the CHRNE gene. Our report highlights
clinical heterogeneity, intrafamily variability in spite of the same genotype and
a possible gender effect; it confirms the efficacy and safety of salbutamol in
patients who harbor mutations in the epsilon subunit of acetylcholine receptor.
PMID- 28690393
TI - Effect on lung function of mounthpiece ventilation in Steinert disease. A case
report.
AB - In patients with muscular dystrophies both muscle length tension relationship
changes and muscle elasticity and plasticity are decreased, resulting in impaired
inspiratory muscle function and decreased vital capacity. Furthermore, the loss
of deep breathing further increases the risk of alveolar collapse,
hypoventilation and atelectasias. In this case report, a stable improvement of
vital capacity after treatment with mounthpiece ventilation (MPV), was observed,
suggesting that not invasive ventilation (NIV) might help to maintai lung and
chest wall compliance, prevent hypoventilation and atelectasias which in turn may
slow down the development of the restrictive respiratory pattern. The improvement
of vital capacity may have a positive impact on alveolar ventilation by reducing
the time with SaO2 values below 90%. This case illustrates that MPV is an
effective method to improve respiratory function in patients non-tolerant of
nasal mask and a valid alternative option for those who need NIV support for the
most part of the day. Furthermore, the use of MPV, alone or combined with other
interfaces, improves the quality of life of the neuromuscular patients and
promotes a greater adherence to mechanical ventilation.
PMID- 28690394
TI - A Software Application for Mining and Presenting Relevant Cancer Clinical Trials
per Cancer Mutation.
AB - ClinicalTrials.org is a popular portal which physicians use to find clinical
trials for their patients. However, the current setup of ClinicalTrials.org makes
it difficult for oncologists to locate clinical trials for patients based on
mutational status. We present CTMine, a system that mines ClinicalTrials.org for
clinical trials per cancer mutation and displays the trials in a user-friendly
Web application. The system currently lists clinical trials for 6 common genes
(ALK, BRAF, ERBB2, EGFR, KIT, and KRAS). The current machine learning model used
to identify relevant clinical trials focusing on the above gene mutations had an
average 88% precision/recall. As part of this analysis, we compared human versus
machine and found that oncologists were unable to reach a consensus on whether a
clinical trial mined by CTMine was "relevant" per gene mutation, a finding that
highlights an important topic which deems future exploration.
PMID- 28690395
TI - An Assessment of Database-Validated microRNA Target Genes in Normal Colonic
Mucosa: Implications for Pathway Analysis.
AB - BACKGROUND: Determination of functional pathways regulated by microRNAs (miRNAs),
while an essential step in developing therapeutics, is challenging. Some miRNAs
have been studied extensively; others have limited information. In this study, we
focus on 254 miRNAs previously identified as being associated with colorectal
cancer and their database-identified validated target genes. METHODS: We use RNA
Seq data to evaluate messenger RNA (mRNA) expression for 157 subjects who also
had miRNA expression data. In the replication phase of the study, we replicated
associations between 254 miRNAs associated with colorectal cancer and mRNA
expression of database-identified target genes in normal colonic mucosa. In the
discovery phase of the study, we evaluated expression of 18 miR-NAs (those with
20 or fewer database-identified target genes along with miR-21-5p, miR-215-5p,
and miR-124-3p which have more than 500 database-identified target genes) with
expression of 17 434 mRNAs to identify new targets in colon tissue. Seed region
matches between miRNA and newly identified targeted mRNA were used to help
determine direct miRNA-mRNA associations. RESULTS: From the replication of the
121 miRNAs that had at least 1 database-identified target gene using mRNA
expression methods, 97.9% were expressed in normal colonic mucosa. Of the 8622
target miRNA-mRNA associations identified in the database, 2658 (30.2%) were
associated with gene expression in normal colonic mucosa after adjusting for
multiple comparisons. Of the 133 miRNAs with database-identified target genes by
non-mRNA expression methods, 97.2% were expressed in normal colonic mucosa. After
adjustment for multiple comparisons, 2416 miRNA-mRNA associations remained
significant (19.8%). Results from the discovery phase based on detailed
examination of 18 miRNAs identified more than 80 000 miRNA-mRNA associations that
had not previously linked to the miRNA. Of these miRNA-mRNA associations, 15.6%
and 14.8% had seed matches for CRCh38 and CRCh37, respectively. CONCLUSIONS: Our
data suggest that miRNA target gene databases are incomplete; pathways derived
from these databases have similar deficiencies. Although we know a lot about
several miRNAs, little is known about other miRNAs in terms of their targeted
genes. We encourage others to use their data to continue to further identify and
validate miRNA-targeted genes.
PMID- 28690396
TI - Prognostic Impact of Urokinase Plasminogen Activator Receptor Expression in
Pancreatic Cancer: Malignant Versus Stromal Cells.
AB - The urokinase plasminogen activator receptor (uPAR) has been proposed as a
potential prognostic factor for various malignancies. The aim of this study is to
assess the prognostic value of uPAR expression in neoplastic and stromal cells of
patients with pancreatic adenocarcinoma. Urokinase plasminogen activator receptor
expression was determined by immunohistochemistry in 122 pancreatic ductal
adenocarcinomas. Kaplan-Meier and Cox regression analyses were used to determine
the association with survival. Respectively 66%, 82% and 62% of patients with
pancreatic cancer expressed uPAR in neoplastic cells, stromal, and in both
combined. Multivariate analysis showed a significant inverse association between
uPAR expression in both neoplastic and stromal cells and overall survival. The
prognostic impact of uPAR in stromal cells is substantial, but not as pronounced
as that of uPAR expression in neoplastic cells. This study suggests a role for
uPAR as a biomarker to single out higher risk subgroups of patients with
pancreatic cancer.
PMID- 28690397
TI - Pesticide Exposure and Health Problems Among Female Horticulture Workers in
Tanzania.
AB - Commercialization of horticulture farming, expansion of farms, and the practice
of monoculture favor the proliferation of pests, which in turn increases the need
for pesticides. Increased exposure to pesticides is associated with inadequate
knowledge on the hazardous nature of pesticides, poor hygiene practices, lack of
availability of washing facilities, and insufficient adherence to precautionary
instructions on pesticide labels. Mitigating the risks posed by pesticides is
considered a less compelling interest than alleviating poverty. Women working in
horticulture in Tanzania usually have low levels of education and income and lack
decision-making power even on matters relating to their own health. This
contributes to pesticide exposure and other health challenges. Because of
multiple factors, some of which act as study confounders, few studies on exposure
to pesticides and health effects have been conducted among women. This review
identified factors that contribute to the increased health effects among women
working in the horticultural industry and how these effects relate to pesticide
exposure.
PMID- 28690399
TI - Facilitating Transfer of Skills and Strategies in Occupational Therapy Practice:
Practical Application of Transfer Principles.
AB - In Occupational Therapy (OT) practice, practitioners assume that the skills and
strategies taught to clients during rehabilitation will transfer to performance
and participation in everyday life. Despite transfer serving as a practice
foundation, outcome studies conclude that this assumption of transfer is not
occurring and it often results in decreased efficacy of rehabilitation. This
paper investigated key aspects of transfer and found concepts in the psychology
literature that can support transfer of skills and strategies in OT. Six key
principles proposed from educational psychology can serve as a guide for
practitioners to better train for transfer. In this paper, we discuss the six
principles and apply concepts from psychology. Each principle is supported with
examples of how they may be incorporated OT practice. If occupational therapists
understand these principles and implement them in treatment, the efficacy of
treatment may improve for many populations.
PMID- 28690398
TI - Intrinsic association between diet and the gut microbiome: current evidence.
AB - The gut microbiome performs many crucial functions for the human host, but the
molecular mechanisms by which host, microbe and diet interact to mediate health
and disease are only starting to be revealed. Here we review the literature on
how changes in the diet affect the microbiome. A number of studies have shown
that within a geographic region, different diets (such as vegan vs. omnivore) are
associated with differences in a modest number of taxa but do not reliably
produce radical differences within the gut microbial community. In contrast,
studies that look across continents consistently find profoundly different
microbial communities between Westernized and traditional populations, although
it remains unclear to what extent diet or other differences in lifestyle drive
these distinct microbial community structures. Furthermore, studies that place
subjects on controlled short term experimental diets have found the resulting
alterations to the gut microbial community to generally be small in scope, with
changes that do not overcome initial individual differences in microbial
community structure. These results emphasize that the human gut microbial
community is relatively stable over time. In contrast, short term changes in diet
can cause large changes in metabolite profiles, including metabolites processed
by the gut microbial community. These results suggest that commensal gut microbes
have a great deal of genetic plasticity and can activate different metabolic
pathways independent of changes to microbial community composition. Thus, future
studies of the how diet impacts host health via the microbiome may wish to focus
on functional assays such as transcriptomics and metabolomics, in addition to 16S
rRNA and whole-genome metagenome shotgun analyses of DNA. Taken together, the
literature is most consistent with a model in which the composition of the adult
gut microbial community undergoes modest compositional changes in response to
altered diet but can nonetheless respond very rapidly to dietary changes via up-
or down-regulation of metabolic pathways that can have profound and immediate
consequences for host health.
PMID- 28690400
TI - Multiaxial constitutive behavior of an interstitial-free steel: Measurements
through X-ray and digital image correlation.
AB - Constitutive behaviors of an interstitial-free steel sample were measured using
an augmented Marciniak experiment. In these tests, multiaxial strain field data
of the flat specimens were measured by the digital image correlation technique.
In addition, the flow stress was measured using an X-ray diffractometer. The flat
specimens in three different geometries were tested in order to achieve 1)
balanced biaxial strain, and plane strain tests with zero strain in either 2)
rolling direction or 3) transverse direction. The multiaxial stress and strain
data were processed to obtain plastic work contours with reference to a uniaxial
tension test along the rolling direction. The experimental results show that the
mechanical behavior of the subjected specimen deviates significantly from
isotropic behavior predicted by the von Mises yield criterion. The initial yield
loci measured by a Marciniak tester is in good agreement with what is predicted
by Hill's yield criterion. However, as deformation increases beyond the vonMises
strain of 0.05, the shape of the work contour significantly deviates from that of
Hill's yield locus. A prediction made by a viscoplastic self-consistent model is
in better agreement with the experimental observation than the Hill yield locus
with the isotropic work-hardening rule. However, none of the studied models
matched the initial or evolving anisotropic behaviors of the interstitial-free
steel measured by the augmented Marciniak experiment.
PMID- 28690401
TI - Is a time symmetric interpretation of quantum theory possible without
retrocausality?
AB - Huw Price has proposed an argument that suggests a time symmetric ontology for
quantum theory must necessarily be retrocausal, i.e. it must involve influences
that travel backwards in time. One of Price's assumptions is that the quantum
state is a state of reality. However, one of the reasons for exploring
retrocausality is that it offers the potential for evading the consequences of no
go theorems, including recent proofs of the reality of the quantum state. Here,
we show that this assumption can be replaced by a different assumption, called
lambda-mediation, that plausibly holds independently of the status of the quantum
state. We also reformulate the other assumptions behind the argument to place
them in a more general framework and pin down the notion of time symmetry
involved more precisely. We show that our assumptions imply a timelike analogue
of Bell's local causality criterion and, in doing so, give a new interpretation
of timelike violations of Bell inequalities. Namely, they show the impossibility
of a (non-retrocausal) time symmetric ontology.
PMID- 28690402
TI - Nonlinear model identification and spectral submanifolds for multi-degree-of
freedom mechanical vibrations.
AB - In a nonlinear oscillatory system, spectral submanifolds (SSMs) are the smoothest
invariant manifolds tangent to linear modal subspaces of an equilibrium.
Amplitude-frequency plots of the dynamics on SSMs provide the classic backbone
curves sought in experimental nonlinear model identification. We develop here, a
methodology to compute analytically both the shape of SSMs and their
corresponding backbone curves from a data-assimilating model fitted to
experimental vibration signals. This model identification utilizes Taken's delay
embedding theorem, as well as a least square fit to the Taylor expansion of the
sampling map associated with that embedding. The SSMs are then constructed for
the sampling map using the parametrization method for invariant manifolds, which
assumes that the manifold is an embedding of, rather than a graph over, a
spectral subspace. Using examples of both synthetic and real experimental data,
we demonstrate that this approach reproduces backbone curves with high accuracy.
PMID- 28690403
TI - On the regularization of impact without collision: the Painleve paradox and
compliance.
AB - We consider the problem of a rigid body, subject to a unilateral constraint, in
the presence of Coulomb friction. We regularize the problem by assuming
compliance (with both stiffness and damping) at the point of contact, for a
general class of normal reaction forces. Using a rigorous mathematical approach,
we recover impact without collision (IWC) in both the inconsistent and the
indeterminate Painleve paradoxes, in the latter case giving an exact formula for
conditions that separate IWC and lift-off. We solve the problem for arbitrary
values of the compliance damping and give explicit asymptotic expressions in the
limiting cases of small and large damping, all for a large class of rigid bodies.
PMID- 28690404
TI - Energy-based analysis of biomolecular pathways.
AB - Decomposition of biomolecular reaction networks into pathways is a powerful
approach to the analysis of metabolic and signalling networks. Current approaches
based on analysis of the stoichiometric matrix reveal information about steady
state mass flows (reaction rates) through the network. In this work, we show how
pathway analysis of biomolecular networks can be extended using an energy-based
approach to provide information about energy flows through the network. This
energy-based approach is developed using the engineering-inspired bond graph
methodology to represent biomolecular reaction networks. The approach is
introduced using glycolysis as an exemplar; and is then applied to analyse the
efficiency of free energy transduction in a biomolecular cycle model of a
transporter protein [sodium-glucose transport protein 1 (SGLT1)]. The overall aim
of our work is to present a framework for modelling and analysis of biomolecular
reactions and processes which considers energy flows and losses as well as mass
transport.
PMID- 28690405
TI - Knotted fields and explicit fibrations for lemniscate knots.
AB - We give an explicit construction of complex maps whose nodal lines have the form
of lemniscate knots. We review the properties of lemniscate knots, defined as
closures of braids where all strands follow the same transverse (1, l) Lissajous
figure, and are therefore a subfamily of spiral knots generalizing the torus
knots. We then prove that such maps exist and are in fact fibrations with
appropriate choices of parameters. We describe how this may be useful in physics
for creating knotted fields, in quantum mechanics, optics and generalizing to
rational maps with application to the Skyrme-Faddeev model. We also prove how
this construction extends to maps with weakly isolated singularities.
PMID- 28690406
TI - The cutting of metals via plastic buckling.
AB - The cutting of metals has long been described as occurring by laminar plastic
flow. Here we show that for metals with large strain-hardening capacity, laminar
flow mode is unstable and cutting instead occurs by plastic buckling of a thin
surface layer. High speed in situ imaging confirms that the buckling results in a
small bump on the surface which then evolves into a fold of large amplitude by
rotation and stretching. The repeated occurrence of buckling and folding
manifests itself at the mesoscopic scale as a new flow mode with significant
vortex-like components-sinuous flow. The buckling model is validated by
phenomenological observations of flow at the continuum level and microstructural
characteristics of grain deformation and measurements of the folding. In addition
to predicting the conditions for surface buckling, the model suggests various
geometric flow control strategies that can be effectively implemented to promote
laminar flow, and suppress sinuous flow in cutting, with implications for
industrial manufacturing processes. The observations impinge on the foundations
of metal cutting by pointing to the key role of stability of laminar flow in
determining the mechanism of material removal, and the need to re-examine long
held notions of large strain deformation at surfaces.
PMID- 28690407
TI - Regularly configured structures with polygonal prisms for three-dimensional
auxetic behaviour.
AB - We report here structures, constructed with regular polygonal prisms, that
exhibit negative Poisson's ratios. In particular, we show how we can construct
such a structure with regular n-gonal prism-shaped unit cells that are again
built with regular n-gonal component prisms. First, we show that the only three
possible values for n are 3, 4 and 6 and then discuss how we construct the unit
cell again with regular n-gonal component prisms. Then, we derive Poisson's ratio
formula for each of the three structures and show, by analysis and numerical
verification, that the structures possess negative Poisson's ratio under certain
geometric conditions.
PMID- 28690408
TI - Wave reflection and transmission in multiply stented blood vessels.
AB - Closed circulatory systems display an exquisite balance between vascular
elasticity and viscous fluid effects, to induce pulse-smoothing and avoid
resonance during the cardiac cycle. Stents in the arterial tree alter this
balance through stiffening and because a periodic structure is introduced,
capable of interacting with the fluid in a complex way. While the former feature
has been investigated, the latter received no attention so far. But periodic
structures are the building blocks of metamaterials, known for their 'non
natural' behaviour. Thus, the investigation of a stent's periodic microstructure
dynamical interactions is crucial to assess possible pathological responses. A
one-dimensional fluid-structure interaction model, simple enough to allow an
analytical solution for situations of interest involving one or two interacting
stents, is introduced. It is determined: (i) whether or not frequency bands exist
in which reflected blood pulses are highly increased and (ii) if these bands are
close to the characteristic frequencies of arteries and finally, (iii) if the
internal structure of the stent can sensibly affect arterial blood dynamics. It
is shown that, while the periodic structure of an isolated stent can induce
anomalous reflection only in pathological conditions, the presence of two
interacting stents is more critical, and high reflection can occur at frequencies
not far from the physiological values.
PMID- 28690409
TI - Turbulent boundary layer under the control of different schemes.
AB - This work explores experimentally the control of a turbulent boundary layer over
a flat plate based on wall perturbation generated by piezo-ceramic actuators.
Different schemes are investigated, including the feed-forward, the feedback, and
the combined feed-forward and feedback strategies, with a view to suppressing the
near-wall high-speed events and hence reducing skin friction drag. While the
strategies may achieve a local maximum drag reduction slightly less than their
counterpart of the open-loop control, the corresponding duty cycles are
substantially reduced when compared with that of the open-loop control. The
results suggest a good potential to cut down the input energy under these control
strategies. The fluctuating velocity, spectra, Taylor microscale and mean energy
dissipation are measured across the boundary layer with and without control and,
based on the measurements, the flow mechanism behind the control is proposed.
PMID- 28690410
TI - Ultrasonic defect characterization using parametric-manifold mapping.
AB - The aim of ultrasonic non-destructive evaluation includes the detection and
characterization of defects, and an understanding of the nature of defects is
essential for the assessment of structural integrity in safety critical systems.
In general, the defect characterization challenge involves an estimation of
defect parameters from measured data. In this paper, we explore the extent to
which defects can be characterized by their ultrasonic scattering behaviour.
Given a number of ultrasonic measurements, we show that characterization
information can be extracted by projecting the measurement onto a parametric
manifold in principal component space. We show that this manifold represents the
entirety of the characterization information available from far-field harmonic
ultrasound. We seek to understand the nature of this information and hence
provide definitive statements on the defect characterization performance that is,
in principle, extractable from typical measurement scenarios. In experiments, the
characterization problem of surface-breaking cracks and the more general problem
of elliptical voids are studied, and a good agreement is achieved between the
actual parameter values and the characterization results. The nature of the
parametric manifold enables us to explain and quantify why some defects are
relatively easy to characterize, whereas others are inherently challenging.
PMID- 28690411
TI - Addressing the discrepancy of finding the equilibrium melting point of silicon
using molecular dynamics simulations.
AB - We performed molecular dynamics simulations to study the equilibrium melting
point of silicon using (i) the solid-liquid coexistence method and (ii) the Gibbs
free energy technique, and compared our novel results with the previously
published results obtained from the Monte Carlo (MC) void-nucleated melting
method based on the Tersoff-ARK interatomic potential (Agrawal et al. Phys. Rev.
B72, 125206. (doi:10.1103/PhysRevB.72.125206)). Considerable discrepancy was
observed (approx. 20%) between the former two methods and the MC void-nucleated
melting result, leading us to question the applicability of the empirical MC void
nucleated melting method to study a wide range of atomic and molecular systems. A
wider impact of the study is that it highlights the bottleneck of the Tersoff-ARK
potential in correctly estimating the melting point of silicon.
PMID- 28690412
TI - Analytical solutions for two-dimensional Stokes flow singularities in a no-slip
wedge of arbitrary angle.
AB - An analytical method to find the flow generated by the basic singularities of
Stokes flow in a wedge of arbitrary angle is presented. Specifically, we solve a
biharmonic equation for the stream function of the flow generated by a point
stresslet singularity and satisfying no-slip boundary conditions on the two walls
of the wedge. The method, which is readily adapted to any other singularity type,
takes full account of any transcendental singularities arising at the corner of
the wedge. The approach is also applicable to problems of plane strain/stress of
an elastic solid where the biharmonic equation also governs the Airy stress
function.
PMID- 28690413
TI - Extensional channel flow revisited: a dynamical systems perspective.
AB - Extensional self-similar flows in a channel are explored numerically for
arbitrary stretching-shrinking rates of the confining parallel walls. The present
analysis embraces time integrations, and continuations of steady and periodic
solutions unfolded in the parameter space. Previous studies focused on the
analysis of branches of steady solutions for particular stretching-shrinking
rates, although recent studies focused also on the dynamical aspects of the
problems. We have adopted a dynamical systems perspective, analysing the
instabilities and bifurcations the base state undergoes when increasing the
Reynolds number. It has been found that the base state becomes unstable for small
Reynolds numbers, and a transitional region including complex dynamics takes
place at intermediate Reynolds numbers, depending on the wall acceleration
values. The base flow instabilities are constitutive parts of different
codimension-two bifurcations that control the dynamics in parameter space. For
large Reynolds numbers, the restriction to self-similarity results in simple
flows with no realistic behaviour, but the flows obtained in the transition
region can be a valuable tool for the understanding of the dynamics of realistic
Navier-Stokes solutions.
PMID- 28690414
TI - A free-boundary model of diffusive valley growth: theory and observation.
AB - Valleys that form around a stream head often develop characteristic finger-like
elevation contours. We study the processes involved in the formation of these
valleys and introduce a theoretical model that indicates how shape may inform the
underlying processes. We consider valley growth as the advance of a moving
boundary travelling forward purely through linearly diffusive erosion, and we
obtain a solution for the valley shape in three dimensions. Our solution compares
well to the shape of slowly growing groundwater-fed valleys found in Bristol,
Florida. Our results identify a new feature in the formation of groundwater-fed
valleys: a spatially variable diffusivity that can be modelled by a fixed-height
moving boundary.
PMID- 28690415
TI - Windowed Green function method for the Helmholtz equation in the presence of
multiply layered media.
AB - This paper presents a new methodology for the solution of problems of two- and
three-dimensional acoustic scattering (and, in particular, two-dimensional
electromagnetic scattering) by obstacles and defects in the presence of an
arbitrary number of penetrable layers. Relying on the use of certain slow-rise
windowing functions, the proposed windowed Green function approach efficiently
evaluates oscillatory integrals over unbounded domains, with high accuracy,
without recourse to the highly expensive Sommerfeld integrals that have typically
been used to account for the effect of underlying planar multilayer structures.
The proposed methodology, whose theoretical basis was presented in the recent
contribution (Bruno et al. 2016 SIAM J. Appl. Math.76, 1871-1898.
(doi:10.1137/15M1033782)), is fast, accurate, flexible and easy to implement. Our
numerical experiments demonstrate that the numerical errors resulting from the
proposed approach decrease faster than any negative power of the window size. In
a number of examples considered in this paper, the proposed method is up to
thousands of times faster, for a given accuracy, than corresponding methods based
on the use of Sommerfeld integrals.
PMID- 28690416
TI - Non-reciprocal wave propagation in modulated elastic metamaterials.
AB - Time-reversal symmetry for elastic wave propagation breaks down in a resonant
mass-in-mass lattice whose inner-stiffness is weakly modulated in space and in
time in a wave-like fashion. Specifically, one-way wave transmission, conversion
and amplification as well as unidirectional wave blocking are demonstrated
analytically through an asymptotic analysis based on coupled mode theory and
numerically thanks to a series of simulations in harmonic and transient regimes.
High-amplitude modulations are then explored in the homogenization limit where a
non-standard effective mass operator is recovered and shown to take negative
values over unusually large frequency bands. These modulated metamaterials, which
exhibit either non-reciprocal behaviours or non-standard effective mass
operators, offer promise for applications in the field of elastic wave control in
general and in one-way conversion/amplification in particular.
PMID- 28690417
TI - The effect of coherent stirring on the advection-condensation of water vapour.
AB - Atmospheric water vapour is an essential ingredient of weather and climate. The
key features of its distribution can be represented by kinematic models which
treat it as a passive scalar advected by a prescribed flow and reacting through
condensation. Condensation acts as a sink that maintains specific humidity below
a prescribed, space-dependent saturation value. To investigate how the interplay
between large-scale advection, small-scale turbulence and condensation controls
moisture distribution, we develop simple kinematic models which combine a single
circulating flow with a Brownian-motion representation of turbulence. We first
study the drying mechanism of a water-vapour anomaly released inside a vortex at
an initial time. Next, we consider a cellular flow with a moisture source at a
boundary. The statistically steady state attained shows features reminiscent of
the Hadley cell such as boundary layers, a region of intense precipitation and a
relative humidity minimum. Explicit results provide a detailed characterization
of these features in the limit of strong flow.
PMID- 28690418
TI - New conformal mapping for adaptive resolving of the complex singularities of
Stokes wave.
AB - A new highly efficient method is developed for computation of travelling periodic
waves (Stokes waves) on the free surface of deep water. A convergence of
numerical approximation is determined by the complex singularities above the free
surface for the analytical continuation of the travelling wave into the complex
plane. An auxiliary conformal mapping is introduced which moves singularities
away from the free surface thus dramatically speeding up numerical convergence by
adapting the numerical grid for resolving singularities while being consistent
with the fluid dynamics. The efficiency of that conformal mapping is demonstrated
for the Stokes wave approaching the limiting Stokes wave (the wave of the
greatest height) which significantly expands the family of numerically accessible
solutions. It allows us to provide a detailed study of the oscillatory approach
of these solutions to the limiting wave. Generalizations of the conformal mapping
to resolve multiple singularities are also introduced.
PMID- 28690419
TI - Correction to 'Homogenized boundary conditions and resonance effects in Faraday
cages'.
AB - [This corrects the article DOI: 10.1098/rspa.2016.0062.].
PMID- 28690420
TI - Brane-World Gravity.
AB - The observable universe could be a 1+3-surface (the "brane") embedded in a 1+3+d
dimensional spacetime (the "bulk"), with Standard Model particles and fields
trapped on the brane while gravity is free to access the bulk. At least one of
the d extra spatial dimensions could be very large relative to the Planck scale,
which lowers the fundamental gravity scale, possibly even down to the electroweak
(~ TeV) level. This revolutionary picture arises in the framework of recent
developments in M theory. The 1+10-dimensional M theory encompasses the known 1+9
dimensional superstring theories, and is widely considered to be a promising
potential route to quantum gravity. At low energies, gravity is localized at the
brane and general relativity is recovered, but at high energies gravity "leaks"
into the bulk, behaving in a truly higher-dimensional way. This introduces
significant changes to gravitational dynamics and perturbations, with interesting
and potentially testable implications for high-energy astrophysics, black holes,
and cosmology. Brane-world models offer a phenomenological way to test some of
the novel predictions and corrections to general relativity that are implied by M
theory. This review analyzes the geometry, dynamics and perturbations of simple
brane-world models for cosmology and astrophysics, mainly focusing on warped 5
dimensional brane-worlds based on the Randall-Sundrum models. We also cover the
simplest brane-world models in which 4-dimensional gravity on the brane is
modified at low energies - the 5-dimensional Dvali-Gabadadze-Porrati models. Then
we discuss co-dimension two branes in 6-dimensional models.
PMID- 28690421
TI - The Kerr/CFT correspondence and its extensions.
AB - We present a first-principles derivation of the main results of the Kerr/CFT
correspondence and its extensions using only tools from gravity and quantum field
theory. Firstly, we review properties of extremal black holes with in particular
the construction of an asymptotic Virasoro symmetry in the near-horizon limit.
The entropy of extremal spinning or charged black holes is shown to match with a
chiral half of Cardy's formula. Secondly, we show how a thermal 2-dimensional
conformal field theory (CFT) is relevant to reproduce the dynamics of near
superradiant probes around near-extremal black holes in the semi-classical limit.
Thirdly, we review the hidden conformal symmetries of asymptotically-flat black
holes away from extremality and present how the non-extremal entropy can be
matched with Cardy's formula. We follow an effective field theory approach and
consider the Kerr-Newman black hole and its generalizations in various
supergravity theories. The interpretation of these results by deformed dual
conformal field theories is discussed and contrasted with properties of standard
2-dimensional CFTs. We conclude with a list of open problems.
PMID- 28690422
TI - Detection methods for stochastic gravitational-wave backgrounds: a unified
treatment.
AB - We review detection methods that are currently in use or have been proposed to
search for a stochastic background of gravitational radiation. We consider both
Bayesian and frequentist searches using ground-based and space-based laser
interferometers, spacecraft Doppler tracking, and pulsar timing arrays; and we
allow for anisotropy, non-Gaussianity, and non-standard polarization states. Our
focus is on relevant data analysis issues, and not on the particular
astrophysical or early Universe sources that might give rise to such backgrounds.
We provide a unified treatment of these searches at the level of detector
response functions, detection sensitivity curves, and, more generally, at the
level of the likelihood function, since the choice of signal and noise models and
prior probability distributions are actually what define the search. Pedagogical
examples are given whenever possible to compare and contrast different
approaches. We have tried to make the article as self-contained and comprehensive
as possible, targeting graduate students and new researchers looking to enter
this field.
PMID- 28690424
TI - Generating subtour elimination constraints for the TSP from pure integer
solutions.
AB - The traveling salesman problem (TSP) is one of the most prominent combinatorial
optimization problems. Given a complete graph [Formula: see text] and non
negative distances d for every edge, the TSP asks for a shortest tour through all
vertices with respect to the distances d. The method of choice for solving the
TSP to optimality is a branch and cut approach. Usually the integrality
constraints are relaxed first and all separation processes to identify violated
inequalities are done on fractional solutions. In our approach we try to exploit
the impressive performance of current ILP-solvers and work only with integer
solutions without ever interfering with fractional solutions. We stick to a very
simple ILP-model and relax the subtour elimination constraints only. The
resulting problem is solved to integer optimality, violated constraints (which
are trivial to find) are added and the process is repeated until a feasible
solution is found. In order to speed up the algorithm we pursue several attempts
to find as many relevant subtours as possible. These attempts are based on the
clustering of vertices with additional insights gained from empirical
observations and random graph theory. Computational results are performed on test
instances taken from the TSPLIB95 and on random Euclidean graphs.
PMID- 28690427
TI - Retraction Note to: Mutation pattern is an influential factor on functional
mutation rates in cancer.
AB - [This retracts the article DOI: 10.1186/s12935-016-0278-5.].
PMID- 28690425
TI - An unsettled bargain? Mothers' perceptions of justice and fairness in paid work.
AB - Mothers' return to work following childbirth is widely recognized as a key stage
in establishing employment arrangements that disadvantage them in the long run.
This article investigates why mothers accept these unequal arrangements using
data from a qualitative study of 109 Australian mothers. It focuses on mothers'
perceptions of the fairness and justice of the flexibility of arrangements they
commonly enter into upon return to work. The article draws attention to the
importance of different justice frameworks, distributive, procedural and
interactional, in understanding women's acceptance of gender inequality in paid
work. The results indicate that most mothers view their workplace arrangements as
fair, consistent with a distributive justice framework. Many women also place
great importance on interactional justice, particularly in their experiences in
negotiating flexibility. The article also identifies differences across
employment type with women in jobs with career prospects more likely to invoke
interactional justice frameworks than women in jobs with few career prospects.
PMID- 28690428
TI - Firms, crowds, and innovation.
AB - The purpose of this article is to suggest a (preliminary) taxonomy and research
agenda for the topic of "firms, crowds, and innovation" and to provide an
introduction to the associated special issue. We specifically discuss how various
crowd-related phenomena and practices-for example, crowdsourcing, crowdfunding,
user innovation, and peer production-relate to theories of the firm, with
particular attention on "sociality" in firms and markets. We first briefly review
extant theories of the firm and then discuss three theoretical aspects of
sociality related to crowds in the context of strategy, organizations, and
innovation: (1) the functions of sociality (sociality as extension of
rationality, sociality as sensing and signaling, sociality as matching and
identity), (2) the forms of sociality (independent/aggregate and
interacting/emergent forms of sociality), and (3) the failures of sociality
(misattribution and misapplication). We conclude with an outline of future
research directions and introduce the special issue papers and essays.
PMID- 28690426
TI - Graphing trillions of triangles.
AB - The increasing size of Big Data is often heralded but how data are transformed
and represented is also profoundly important to knowledge discovery, and this is
exemplified in Big Graph analytics. Much attention has been placed on the scale
of the input graph but the product of a graph algorithm can be many times larger
than the input. This is true for many graph problems, such as listing all
triangles in a graph. Enabling scalable graph exploration for Big Graphs requires
new approaches to algorithms, architectures, and visual analytics. A brief
tutorial is given to aid the argument for thoughtful representation of data in
the context of graph analysis. Then a new algebraic method to reduce the
arithmetic operations in counting and listing triangles in graphs is introduced.
Additionally, a scalable triangle listing algorithm in the MapReduce model will
be presented followed by a description of the experiments with that algorithm
that led to the current largest and fastest triangle listing benchmarks to date.
Finally, a method for identifying triangles in new visual graph exploration
technologies is proposed.
PMID- 28690429
TI - 3D Printer Generated Tissue iMolds for Cleared Tissue Using Single- and Multi
Photon Microscopy for Deep Tissue Evaluation.
AB - BACKGROUND: Pathological analyses and methodology has recently undergone a
dramatic revolution. With the creation of tissue clearing methods such as CLARITY
and CUBIC, groups can now achieve complete transparency in tissue samples in nano
porous hydrogels. Cleared tissue is then imagined in a semi-aqueous medium that
matches the refractive index of the objective being used. However, one major
challenge is the ability to control tissue movement during imaging and to
relocate precise locations post sequential clearing and re-staining. METHODS:
Using 3D printers, we designed tissue molds that fit precisely around the
specimen being imaged. First, images are taken of the specimen, followed by
importing and design of a structural mold, then printed with affordable plastics
by a 3D printer. RESULTS: With our novel design, we have innovated tissue molds
called innovative molds (iMolds) that can be generated in any laboratory and are
customized for any organ, tissue, or bone matter being imaged. Furthermore, the
inexpensive and reusable tissue molds are made compatible for any microscope such
as single and multi-photon confocal with varying stage dimensions. Excitingly,
iMolds can also be generated to hold multiple organs in one mold, making
reconstruction and imaging much easier. CONCLUSIONS: Taken together, with iMolds
it is now possible to image cleared tissue in clearing medium while limiting
movement and being able to relocate precise anatomical and cellular locations on
sequential imaging events in any basic laboratory. This system provides great
potential for screening widespread effects of therapeutics and disease across
entire organ systems.
PMID- 28690430
TI - Neurogaming Technology Meets Neuroscience Education: A Cost-Effective, Scalable,
and Highly Portable Undergraduate Teaching Laboratory for Neuroscience.
AB - Active research-driven approaches that successfully incorporate new technology
are known to catalyze student learning. Yet achieving these objectives in
neuroscience education is especially challenging due to the prohibitive costs and
technical demands of research-grade equipment. Here we describe a method that
circumvents these factors by leveraging consumer EEG-based neurogaming technology
to create an affordable, scalable, and highly portable teaching laboratory for
undergraduate courses in neuroscience. This laboratory is designed to give
students hands-on research experience, consolidate their understanding of key
neuroscience concepts, and provide a unique real-time window into the working
brain. Survey results demonstrate that students found the lab sessions engaging.
Students also reported the labs enhanced their knowledge about EEG, their course
material, and neuroscience research in general.
PMID- 28690431
TI - A Protocol Demonstrating 60 Different Drosophila Behaviors in One Assay.
AB - The fruit fly Drosophila melanogaster performs many behaviors, from simple motor
actions to complex social interactions, that are of interest to neurobiologists
studying how the brain controls behavior. Here, an undergraduate laboratory
exercise uses cutting-edge methods to activate sets of neurons thermogenetically,
triggering 60 different behaviors. Students learn how to recognize this large
repertoire of behaviors from 16 fly strains that are publicly available, and from
a large set of training videos provided here. A full protocol, timeline and
handouts are included. Instructors need not have any experience working with
flies. Student feedback is reported; in our experience, students are fascinated
and highly engaged by watching animals perform such a broad array of behaviors.
This exercise teaches fly husbandry and crossing, careful scientific observation,
and principles of behavioral screening.
PMID- 28690432
TI - An Algebra-Based Introductory Computational Neuroscience Course with Lab.
AB - A course in computational neuroscience has been developed at Ohio Wesleyan
University which requires no previous experience with calculus or computer
programming, and which exposes students to theoretical models of neural
information processing and techniques for analyzing neural data. The exploration
of theoretical models of neural processes is conducted in the classroom portion
of the course, while data analysis techniques are covered in lab. Students learn
to program in MATLAB and are offered the opportunity to conclude the course with
a final project in which they explore a topic of their choice within
computational neuroscience. Results from a questionnaire administered at the
beginning and end of the course indicate significant gains in student facility
with core concepts in computational neuroscience, as well as with analysis
techniques applied to neural data.
PMID- 28690433
TI - Recognition Without Words: Using Taste to Explore Survival Processing.
AB - Many educational demonstrations of memory and recall employ word lists and number
strings; items that lend themselves to semantic organization and "chunking." By
applying taste recall to the adaptive memory paradigm, which evaluates memory
from a survival-based evolutionary perspective, we have developed a simple,
inexpensive exercise that defies mnemonic strategies. Most adaptive memory
studies have evaluated recall of words encountered while imagining survival and
non-survival scenarios. Here, we've left the lexical domain and hypothesized that
taste memory, as measured by recognition, would be best when acquisition occurs
under imagined threat of personal harm, namely poisoning. We tested participants
individually while they evaluated eight teas in one of three conditions: in one,
they evaluated the toxicity of the tea (survival condition), in a second, they
considered the marketability of the tea and, in the third, they evaluated the
bitterness of the tea. After a filler task, a surprise recognition task required
the participants to taste and identify the eight original teas from a group of 16
that included eight novel teas. The survival condition led to better recognition
than the bitterness condition but, surprisingly, it did not yield better
recognition than the marketing condition. A second experiment employed a
streamlined design more appropriate for classroom settings and failed to support
the hypothesis that planning enhanced recognition in survival scenarios. This
simple technique has, at least, revealed a robust levels-of-processing effect for
taste recognition and invites students to consider the adaptive advantages of all
forms of memory.
PMID- 28690434
TI - Don't Believe the Gripe! Increasing Course Structure in a Large Non-majors
Neuroscience Course.
AB - Active teaching is increasingly accepted as a better option for higher education
STEM courses than traditional lecture-based instruction. However, concerns remain
regarding student preferences and the impact of increased course structure on
teaching evaluations. Undergraduates in a non-majors neuropharmacology course
were enrolled in an enriched blended course format, providing online case-based
learning opportunities in a large lecture hall setting. Students working in small
assigned groups solved weekly case studies developed to teach basic
neuropharmacology concepts. All case study assignments were peer reviewed and
content was further reinforced with a weekly online quiz. A comparison of scores
on equivalent midterm and final exam questions revealed that students enrolled in
the High-Structure course scored better than students from the previous year that
took a more traditional Low-Structure lecture-based course. Student performance
increased significantly for exam questions that required Bloom's level
understanding. When surveyed, students in the High-Structure course reported some
regret for the lack of traditional lecture and revealed some disapproval towards
the extra work required for active teaching and peer review. Yet, we saw no
change in quantitative instructor evaluation between sections, challenging the
idea that student resistance towards increased work lowers course evaluation
scores. Future instructors using active learning strategies may benefit from
revealing to students the value of increased course structure on performance
outcomes compared with traditional lecture courses.
PMID- 28690435
TI - Redesigning a Neuroscience Laboratory Course for Multiple Sections: An Action
Research Project to Engage Students.
AB - The purpose of our action research project was to improve students' motivation in
a multi-section introductory neuroscience laboratory course. In this paper, we
present: (a) how we collected data related to students' motivation and
engagement, (b) how we analyzed and used the data to make modifications to the
courses, (c) the results of the course modifications, and (d) some possible
explanations for our results. Our aim is not only to provide the results of our
study, but also to explain the process that we used, with the hopes that other
instructors can use similar approaches to improve students' motivation in their
courses. Our attempts to improve students' motivation-related perceptions were
successful in some instances, but not in others. Of particular note was our
finding that some of the students' perceptions varied even though the course
syllabus was the same across sections. We attributed this variation to the
learning environment developed by the teaching assistants (TAs) who taught the
different sections. We provide some strategies that faculty instructors can use
to redesign courses with high enrollments and help TAs motivate their students.
PMID- 28690436
TI - A Rat Model of Fetal Alcohol Syndrome: A Series of Undergraduate Laboratory
Exercises for Biopsychology Courses.
AB - Many undergraduate students are aware that consuming alcohol during pregnancy can
result in many serious physical and behavioral deficits. Student interest in this
clinical syndrome allows instructors to provide engaging laboratory exercises
that relate topics covered in most biopsychology courses to Fetal Alcohol
Syndrome (FAS). Through this series of experiments, students will use rodents to
study the behavioral deficits that can be caused by developmental alcohol
exposure, including impaired ultrasonic vocalizations, hyperactivity, balance,
and spatial learning. Other possible exercises include analyzing blood alcohol
concentrations (BACs), completing histological studies of anatomical effects,
and/or discussing the societal implications of developmental alcohol exposure.
The instructor has the flexibility to determine which of the exercises fit into
the class schedule and budget since he or she may choose to complete all of the
behavioral tests or only one of them. Students will also learn about the benefits
and drawbacks of animal models for human disorders, important considerations in
research design such as reliability and validity, while also gaining experience
in statistical analyses and writing empirical research papers. The application of
these important concepts to a human syndrome and the use of small, easy-to-handle
rodent pups make these exercises an accessible, stimulating introduction to
animal research for most undergraduate students.
PMID- 28690437
TI - The Use of Modular, Electronic Neuron Simulators for Neural Circuit Construction
Produces Learning Gains in an Undergraduate Anatomy and Physiology Course.
AB - During the spring of 2016 at the University of Wisconsin-Milwaukee, we
implemented a novel educational technology designed to teach undergraduates about
the nervous system while allowing them to physically construct their own neural
circuits. Modular, electronic neuron simulators called NeuroBytes were used by
the students in BIOSCI202 Anatomy and Physiology I, a four-credit course
consisting of three hours per week each of lecture and laboratory time. 162
students participated in the laboratory sessions that covered reflexes; 83 in the
experimental sections used the NeuroBytes to build a model of the patellar tendon
reflex, while 79 in the control sections participated in alternate reflex
curricula. To address the question of whether or not the NeuroBytes-based
patellar tendon reflex simulation brought about learning gains, the control and
experimental group students underwent pre/post testing before and after their
laboratory sections. We found that for several of the neuroscience and physiology
concepts assessed on the test, the experimental group students had significantly
greater declarative learning gains between the pre- and post-test as compared to
the control group students. While there are numerous virtual neuroscience
education tools available to undergraduate educators, there are relatively few
designed to engage students in the basics of electrophysiology and neural
circuitry using physical manipulatives, and none to our knowledge that allow them
to build circuits from functioning hand-held "neurons."
PMID- 28690438
TI - A Critical Thinking Activity on Drug Tolerance for Undergraduate Neuroscience
Courses.
AB - Active teaching techniques that involve critical thinking and analysis lead to
better learning and retention, and there is growing need for learner-centered
classroom activities in the neurosciences. This article presents a critical
thinking activity that offers context and meaning to basic principles of synaptic
pharmacology. Students analyze fictional datasets to identify major
characteristics of drug tolerance. Students' self-reported perceptions and
ungraded quiz scores suggest that this activity was an enjoyable and impactful
way to deepen students' understanding and engage them with the course material.
This activity was developed for a 300-level psychopharmacology course that
included majors from various science departments, but could be used and/or
modified for specialized seminars or other undergraduate courses in psychology or
biology.
PMID- 28690439
TI - Grasshopper DCMD: An Undergraduate Electrophysiology Lab for Investigating Single
Unit Responses to Behaviorally-Relevant Stimuli.
AB - Avoiding capture from a fast-approaching predator is an important survival skill
shared by many animals. Investigating the neural circuits that give rise to this
escape behavior can provide a tractable demonstration of systems-level
neuroscience research for undergraduate laboratories. In this paper, we describe
three related hands-on exercises using the grasshopper and affordable technology
to bring neurophysiology, neuroethology, and neural computation to life and
enhance student understanding and interest. We simplified a looming stimuli
procedure using the Backyard Brains SpikerBox bioamplifier, an open-source and
low-cost electrophysiology rig, to extracellularly record activity of the
descending contralateral movement detector (DCMD) neuron from the grasshopper's
neck. The DCMD activity underlies the grasshopper's motor responses to looming
monocular visual cues and can easily be recorded and analyzed on an open-source
iOS oscilloscope app, Spike Recorder. Visual stimuli are presented to the
grasshopper by this same mobile application allowing for synchronized recording
of stimuli and neural activity. An in-app spike-sorting algorithm is described
that allows a quick way for students to record, sort, and analyze their data at
the bench. We also describe a way for students to export these data to other
analysis tools. With the protocol described, students will be able to prepare the
grasshopper, find and record from the DCMD neuron, and visualize the DCMD
responses to quantitatively investigate the escape system by adjusting the speed
and size of simulated approaching objects. We describe the results from 22
grasshoppers, where 50 of the 57 recording sessions (87.7%) had a reliable DCMD
response. Finally, we field-tested our experiment in an undergraduate
neuroscience laboratory and found that a majority of students (67%) could perform
this exercise in one two-hour lab setting, and had an increase in interest for
studying the neural systems that drive behavior.
PMID- 28690440
TI - Locate the Lesion: A Project-Based Learning Case that Stimulates Comprehension
and Application of Neuroanatomy.
AB - A fictitious patient, Mr. Challenge, is admitted to the emergency room and
displays symptoms consistent with damage to the central nervous system. In this
problem-based learning case, students are challenged to determine the location of
a lesion that is consistent with Mr. Challenge's symptoms. Students discover
details about Mr. Challenge's symptoms while exploring three anatomical pathways:
corticospinal tract, spinothalamic tract and medial lemniscal pathway. Students
make predictions as to which of these pathways may be damaged in Mr. Challenge
and defend their predictions based on their research of the function and
anatomical location of these tracts. This ultimately leads the student to
identifying a single lesion site that can account for Mr. Challenge's symptoms.
This case is executed in an undergraduate neuroscience course and would be useful
in anatomy and physiology course, as well as other courses that serve students
interested in health science related careers.
PMID- 28690441
TI - Drugs & the Brain: Case-based Instruction for an Undergraduate Neuropharmacology
Course.
AB - In order to transform a traditional large non-majors general education (GE)
neurobiology lecture (Drugs & the Brain) into an active learning course, we
developed a series of directed mini-cases targeting major drug classes. Humorous
and captivating case-based situations were used to better engage and motivate
students to solve problems related to neuropharmacology and physiology. Here we
provide directed cases, questions and learning outcomes for our opiates mini
cases. In addition, we describe how case studies were incorporated into our
course and assessed using peer review and online quizzing. An in-depth analysis
of the overall course transformation on student exam performance, opinions and
instructor evaluations can be found in the JUNE article Don't Believe the Gripe!
Increasing Course Structure in a Large Non-majors Neuroscience Course.
PMID- 28690442
TI - 25 Years of FUN!
AB - Dr. Julio J. Ramirez, the founding president of the Faculty for Undergraduate
Neuroscience (FUN), shared the comments below on November 13, 2016 at the 25th
Anniversary of FUN's founding, when Drs. Sally Frutiger, Stephen George, Julio
Ramirez, and Dennison Smith were recognized with the Founders Award for their
efforts in launching FUN in 1991.
PMID- 28690443
TI - A Guide for Undergraduates to the Society for Neuroscience Annual Meeting.
AB - The annual meeting of the Society for Neuroscience (SfN) attracts over 30,000
attendees, including many of the world's most accomplished researchers. Although
it can be intimidating to attend a conference of this scale, there are many
rewards for undergraduates. Based on surveys of young neuroscientists, we provide
planning strategies to ensure attendees maximize their exposure and retention of
the breadth and depth offered by this large conference format without becoming
overwhelmed.
PMID- 28690445
TI - Teach Local, Think global: Best Practices in Neuroscience Education Without Big
Budgets.
PMID- 28690444
TI - The Benefits of a Real-Time Web-Based Response System for Enhancing Engaged
Learning in Classrooms and Public Science Events.
AB - Large introduction to neuroscience classes and small science cafes have the same
goal: bridging the gap between the presenter and the audience to convey the
information while being engaging. Early classroom response systems became the
cornerstone of flipped and engaged learning. These "clickers" helped turn
lectures into dialogues, allowing the presenter to become a facilitator rather
than a "sage on the stage." Rapid technological developments, especially the
increase of computing power opened up new opportunities, moving these systems
from a clicker device onto cellphones and laptops. This allowed students to use
their own devices, and instructors to use new question types, such as clicking on
a picture or ranking concepts. A variety of question types makes the learning
environment more engaging, allows better examples for creative and critical
thinking, and facilitates assessment. Online access makes these response systems
scalable, bringing the strength of formative assessments and surveys to public
science communication events, neuroscience journal clubs and distance learning.
In addition to the new opportunities, online polling systems also create new
challenges for the presenters. For example, allowing mobile devices in the
classroom can be distracting. Here, a web-based, real-time response system called
Poll Everywhere was compared to iClickers, highlighting the benefits and the
pitfalls of both systems. In conclusion, the authors observe that the benefits of
web-based response systems outweigh the challenges, and this form of digital
pedagogy can help create a rich dialogue with the audience in large classrooms as
well as in public science events.
PMID- 28690446
TI - Making Primary Literature Come Alive in the Classroom.
AB - By the time young scholars graduate college, they are expected to be prepared for
their career. The knowledge that they have gained during their undergraduate
education is assumed to prepare them for their future occupation. Understanding
primary academic literature is absolutely imperative for scientists who are
expected to be able to read, understand, explain, and incorporate literature into
their work. Unfortunately, many new graduates are only exposed to traditional
learning methods such as textbook readings, lectures, or slide shows about
primary literature. It is important that while in college, students learn about
the rich content of the literature that serves as the foundation for their
respective fields. We review methods for integrating primary literature into the
classroom and separate them into three components including (1) introduction to
the literature, (2) enhancement of literacy and comprehension, (3) and humanizing
the literature. These methods of teaching and learning are far more captivating
than simply memorizing facts for a test. The brilliance of these methods is that
they can be completed within one class time or throughout a semester. The goal is
to help students become comfortable with literature, which does not have to be
restricted by any time frame. It is our hope that this review of existing tools
and ideas provided will help set students up for success in their field. They
allow students to practice knowing and using primary literature while requiring
students to be active participants in scientific discovery related to their
future occupation.
PMID- 28690447
TI - The Missing Manuscript of Dr. Jose Delgado's Radio Controlled Bulls.
AB - Neuroscience systems level courses teach: 1) the role of neuroanatomical
structures of the brain for perception, movement, and cognition; 2) methods to
manipulate and study the brain including lesions, electrophysiological
recordings, microstimulation, optogenetics, and pharmacology; 3) proper
interpretation of behavioral data to deduce brain circuit operation; and 4) the
similarities, differences, and ethics of animal models and their relation to
human physiology. These four topics come together quite dramatically in Dr. Jose
Delgado's 1960s famous experiments on the neural correlates of aggression in
which he stopped bulls in mid-charge by electrically stimulating basal ganglia
and thalamic structures. Technical documentation on these experiments is famously
difficult to find. Here I translate and discuss a Spanish language article
written by Dr. Delgado in 1981 for an encyclopedia on bull fighting published in
Madrid. Here Dr. Delgado appears to give the most complete explanation of his
experiments on microstimulation of bovine brains. Dr. Delgado's motivations,
methods, and his interpretation of the bull experiments are summarized, as well
as some accompanying information from his 1970 English language book: "Physical
Control of the Mind." This review of Dr. Delgado's written work on the bull
experiments can provide a resource to educators and students who desire to learn
more about and interpret the attention-calling experiments that Dr. Delgado did
on a ranch in Andalucia over 50 years ago.
PMID- 28690449
TI - GASTRO-HEP News.
PMID- 28690448
TI - Hepatitis B.
PMID- 28690451
TI - New Direct-Acting Antiviral Agents and Immunomodulators for Hepatitis B Virus
Infection.
AB - Chronic hepatitis B (CHB) affects over 350 million individuals worldwide and is
the most common cause of liver cancer. In the United States, CHB affects at least
2 to 3 million individuals, and current therapies can control the disease but not
cure it. There are over 30 new molecules being studied in CHB in preclinical to
phase 2 studies, targeting specific parts of the hepatitis B virus (HBV) life
cycle and the host immune response. When discussing new therapies for CHB, it is
critical to understand both the various phases of CHB and the life cycle of HBV.
This article will discuss both of these issues, as well as mechanisms of action
of potential therapies and possible ways to combine such therapies in the various
phases of CHB.
PMID- 28690453
TI - Use of the Liver Imaging Reporting and Data System in Hepatocellular Carcinoma.
PMID- 28690452
TI - Advances in the Diagnosis and Management of Colonic Dysplasia in Patients With
Inflammatory Bowel Disease.
AB - The prevalence of colorectal cancer (CRC) in inflammatory bowel disease (IBD) is
estimated at 3.7%. Risk factors for CRC include more severe disease (as reflected
by the extent of disease and the duration of poorly controlled disease), family
history of CRC, pseudopolyps, primary sclerosing cholangitis, and male sex. In
addition, both early and late onset of IBD have been shown to be risk factors in
different studies. Most societal guidelines recommend initiation of surveillance
colonoscopy at 8 to 10 years after IBD symptom onset, followed by subsequent
surveillance in 1- to 2-year intervals. A recent paradigm shift has led to a
focus on targeted biopsies using high-definition colonoscopy or chromoendoscopy
rather than traditional white-light endoscopy, as most dysplasia has proven to be
visible with these advances in technology. With this shift, endoscopic resection
of focal dysplasia, rather than early recommendation for colectomy, has become
commonplace. Future studies should focus on newer methods of dysplasia detection,
along with comparative effectiveness trials, to determine the optimal approach.
Individual risk stratification may also prove beneficial in determining optimal
surveillance strategies and intervals.
PMID- 28690454
TI - Endoscopic Removal of Polyps in the Gastrointestinal Tract.
PMID- 28690450
TI - The Role of Chromoendoscopy in Evaluating Colorectal Dysplasia.
AB - Chromoendoscopy pertains to image-enhanced endoscopic techniques such as dye
based chromoendoscopy and electronic chromoendoscopy using narrow-band imaging,
flexible spectral imaging color enhancement, and i-scan. Dye-based
chromoendoscopy has been demonstrated to improve colorectal dysplasia detection
in high-risk patients with long-term inflammatory bowel disease, and electronic
chromoendoscopy techniques have been shown to improve characterization of
diminutive colorectal lesions, allowing for optical diagnosis during a
colonoscopy examination. This article reviews endoscopic imaging using
chromoendoscopy techniques for colorectal dysplasia evaluation.
PMID- 28690455
TI - Medical Homes for Patients With Inflammatory Bowel Disease.
PMID- 28690456
TI - Diagnosis of Nonalcoholic Steatohepatitis Without Liver Biopsy.
PMID- 28690457
TI - An Overview of Dietary Therapies for the Treatment of Eosinophilic Esophagitis.
PMID- 28690458
TI - The Value of a Closer Look.
PMID- 28690460
TI - Analysis of Player Statistics in Major League Baseball Players Before and After
Achilles Tendon Repair.
AB - BACKGROUND: No currently available literature evaluates the effect of Achilles
tendon repair on professional baseball players in the Major League Baseball
(MLB). QUESTIONS/PURPOSES: The purpose of this study was to determine the impact
of Achilles tendon rupture and repair on MLB players in terms of return to play
and batting/fielding performance metrics. METHODS: Achilles tendon rupture data
were retrospectively collected using information from the MLB disabled list,
injury reports, MLB game summaries, player profiles, and publicly available news
articles. Four pair-matched control MLB position players were selected for each
of the players who underwent advanced analysis. Baseline characteristics were
compared between injured players and controls using Fisher's exact or Student's t
test. RESULTS: Overall, the incidence of Achilles tendon rupture reported in MLB
has increased substantially since 1996. Rate of return to play in MLB after
Achilles tendon rupture and repair is 62% for position players (non-pitchers) who
suffer the injury. There was no association of injury with any player metric.
Compared with injury to the non-power side, injury to the power side was
associated with fewer plate appearances, fewer triples, an increase in percentage
of at-bats with strikeouts, and decreased speed score. CONCLUSION: The incidence
of Achilles tendon rupture in MLB has increased substantially since 1996. While
comparison suggests that overall Achilles tendon injury does not have an effect
on MLB player statistics in the years following surgical repair, subset analysis
of injury to the rear (power-generating) leg may lead to a decline in those
statistics which denote a player's speed and running ability.
PMID- 28690459
TI - Functional Outcomes of Modular Conversion of Hemiarthroplasty or Total to Reverse
Total Shoulder Arthroplasty.
AB - BACKGROUND: The advent of modular shoulder arthroplasty systems has allowed the
conversion of hemiarthroplasty or total shoulder arthroplasty to reverse total
shoulder arthroplasty (RTSA) without removing a well-fixed stem.
QUESTIONS/PURPOSES: To determine the feasibility, functional outcome, and
complication profile of RTSA modular conversion. METHODS: A prospective shoulder
arthroplasty registry was queried for consecutive patients scheduled for a
modular conversion from January 1, 2007, to April 1, 2015. Eligible patients had
medical charts and operative records reviewed for preoperative diagnosis, age,
medical comorbidities, preoperative American Shoulder and Elbow Society (ASES)
score, preoperative Visual Analogue Scale (VAS) pain and instability scores, and
intraoperative findings. Each patient was then contacted by telephone or mail to
complete up-to-date ASES and VAS questionnaires. RESULTS: Seventeen patients
underwent a modular conversion. Nine patients were scheduled for modular
conversion but underwent humeral revision due to excessive soft tissue tension
(65.3% modular conversion rate). Average follow-up was 37.4 months (range 10.0
67.6 months). Pain scores improved from 5.3 (range 0.4 to 8.0) to 2.4 (range 0 to
9.3) (p < 0.01), instability VAS from 5.2 (range 0 to 10) to 1.1 (range 0 to 6.8)
(p < 0.01), and ASES scores improved from 35.2 (range 20.7 to 61.3) to 65.6
(range 11.8 to 92) (p < 0.01). CONCLUSIONS: Modular conversion of an anatomic to
a RTSA is feasible in a majority of patients. Despite the complexity of the
procedure, modular conversion of hemiarthroplasty or TSA to RTSA can
significantly improve functional outcomes with a low rate of complications.
PMID- 28690461
TI - Hospital for Special Surgery ACL Registry: 2-Year Outcomes Suggest Low Revision
and Return to OR Rates.
AB - BACKGROUND: Anterior cruciate ligament (ACL) injuries are among the most common
knee injuries. Patient outcomes, rate of subsequent operations, and rate of
subsequent ACL reconstruction following primary ACL reconstruction need to be
evaluated. QUESTIONS/PURPOSES: This study was designed to answer the following
questions: (1) What is the return to surgery (OR) rate following primary ACL
reconstruction and (2) what is the revision ACL reconstruction rate? METHODS:
Data was drawn from the Hospital for Special Surgery (HSS) ACL Registry.
International Knee Documentation Committee (IKDC) Subjective Knee Evaluation,
Lysholm-Tegner Scales, Marx Activity Scale, and SF12 were completed by patients
at baseline, 1-, and 2-year follow-up. Clinical data and intraoperative data were
registered by surgeons on an intraoperative form. Subsequent surgery rates were
determined by evaluating the medical records for subsequent surgery, laterality,
surgeon, procedure description, and type of anesthesia. RESULTS: The majority of
the ACL reconstructions performed were autograft (76.6%) with the most common
graft being bone-patellar tendon-bone (BTB) autograft (47.2%), hamstring
autograft (21.9%), and Achilles allograft (18.2%). Average IKDC score improved
from 51.9 (SD 16.1) at baseline to 83.5 (SD 14.2) at 2-year follow-up. Females
had a 2.5-point lower IKDC and 1.4-point Marx scores compared to males. Of the
enrolled patients, 7.3% had revision ACL surgery with 70.4% being ipsilateral ACL
surgery. Of the enrolled patients, 10.3% had subsequent knee surgery with 72.3%
being ipsilateral knee surgery. Multivariable logistic regression analysis showed
that patients less than 18 years of age at the time of their index surgery were
over three times more likely to undergo a revision ACL reconstruction compared to
older patients and were at four times higher risk than older patients for any
subsequent knee surgery. CONCLUSION: Understanding ACL surgery, patient outcomes,
and risk factors for revision ACL surgery and subsequent knee surgery after
primary ACL reconstruction is essential. Patients less than 18 years of age have
a higher risk of subsequent knee surgery and subsequent ACL surgery than older
patients.
PMID- 28690462
TI - Open Wedge Distal Femoral Osteotomy: Accuracy of Correction and Patient Outcomes.
AB - BACKGROUND: There is a renewed interest in joint preservation surgery, and
lateral opening wedge distal femoral osteotomy (DFO), a joint-preserving
procedure, has been used to treat symptomatic genu valgum when the deformity
originates in the distal femur. QUESTIONS/PURPOSES: This study aimed to measure
the accuracy of lateral opening wedge DFO in achieving deformity correction using
radiographic parameters. In addition, the ability of lateral opening wedge DFO to
improve patient outcomes as measured by Short Form Health Survey (SF-36) scores
and American Academy of Orthopedic Surgeons (AAOS) lower limb module (LLM) scores
leading to successful joint preservation was assessed. METHODS: The clinical
charts and radiographs of 28 consecutive patients that underwent 41 DFOs (15
unilateral and 13 staged bilateral) using a locking plate construct were
retrospectively reviewed. The mean age of patients undergoing DFO was 44 years
(range 22-72), and 22 of the patients were female. The mean follow-up was 26
months (range 12-57 months). Preoperative and postoperative radiographs were
evaluated for mechanical axis deviation (MAD), lateral distal femoral angle
(LDFA), and the patella congruence angle (PCA). These measurements were compared
to determine the accuracy of deformity correction. Clinical outcomes were
assessed with preoperative and postoperative SF-36 and AAOS LLM, as well as
Oxford knee scores at follow-up. RESULTS: The accuracy of deformity correction
was 95%. The MAD significantly improved from 25.3 mm lateral to the midline to 8
mm medial to the midline (p < 0.01). The LDFA significantly improved from 83.4
degrees to 91.7 degrees (p < 0.01). The PCA significantly improved from 30.4
degrees lateral to 5.7 degrees lateral (p = 0.02). Mean SF-36 scores
significantly improved from 37.5 to 50.2 (p = 0.01); mean LLM scores improved
from 71.6 to 85.9 (p = 0.021), and the mean postoperative Oxford knee score was
35 +/- 6.2 (range 23-46). No patients required total knee arthroplasty at the
time of final follow-up. CONCLUSION: Opening wedge lateral DFO is a reliable
procedure for the treatment of valgus knee malalignment with or without arthritic
changes in the lateral compartment. Deformity correction is accurate, and patient
outcomes reveal significant improvement after surgery. Longer follow-up is
required to access the survivorship of this procedure.
PMID- 28690463
TI - In Vivo Plantar Pressures in Adult-Acquired Flatfoot Compared to Control Using an
Intraoperative Pedobarographic Device.
AB - BACKGROUND: Intraoperative pedobarography has the potential to aid surgical
decisions, but no parameters exist to guide its use. QUESTIONS/PURPOSES: This
study compared supine plantar pressures between flatfoot patients and controls
using a previously validated intraoperative pedobarographic device and examined
associations between supine, walking, and standing plantar pressures. METHODS:
Ten preoperative patients with stage II adult-acquired flatfoot deformity (AAFD)
were compared to ten healthy controls. Supine plantar pressures were assessed
using the pedobarographic device. Standing and walking plantar pressures were
assessed with an EMED-XT sensor array (Novel). Maximum force (MF) and peak
pressure (PP) were calculated for nine anatomical foot regions adjusting for age
and BMI. RESULTS: No differences in plantar pressures were found between flatfoot
patients and controls in the supine or standing positions. During walking,
flatfoot patients had greater MF of the first, second, and third metatarsals (p
<= 0.018) and greater PP of the first and second metatarsals than controls (p <=
0.010). Supine MF and PP were both strongly positively correlated with their
respective pressure measurements for both standing and walking in multiple foot
regions (p <= 0.05, all analyses). Correlations in the first metatarsal region
were generally weak and not statistically significant. CONCLUSION: This device
did not show differences in supine plantar pressures of flatfoot patients and
healthy subjects, highlighting the limitations of intraoperative devices in
guiding flatfoot correction. The differences between flatfoot and controls during
walking and the correlations between supine and walking conditions suggest that
dynamic plantar pressures are a more useful parameter in guiding flatfoot
reconstruction.
PMID- 28690464
TI - Post-Dural Puncture Headache is Uncommon in Young Ambulatory Surgery Patients.
AB - BACKGROUND: The incidence of post-dural puncture headache (PDPH) arising from
spinal anesthesia in the general population is low. However, patients under 45
years have been shown to exhibit a higher incidence of PDPH, even with small
needles. QUESTIONS/PURPOSES: This study aimed to estimate the incidence of PDPH
from a 27G pencil-point needle in ambulatory surgery patients between the ages of
15-45 years and compare incidence of PDPH by age group, sex, and history of
headache. METHODS: In this prospective cohort study, 300 patients (15-45 years
old) who underwent simple knee arthroscopy under spinal anesthesia with a 27G
pencil-point needle were enrolled. Verbal consent was obtained during the initial
phone conversation between post-operative days (PODs) 2-5. A PDPH questionnaire
was administered during this conversation and between PODs 7-10. Patients who
reported a positional headache were contacted by a physician co-investigator, who
determined PDPH diagnosis. RESULTS: Five patients were excluded from analysis due
to complicated operative procedures or spinal needle size. The overall PDPH
incidence was 2.0% (95% CI 0.9-4.4; 6/295). PDPH incidence in 15-19-year-old
patients was 16.7% (95% CI 4.7-44.8; 2/12). The crude relative risk of PDPH was
15.4 (95% CI 2.8-114.4) for patients with and without history of headache and 2.5
(95% CI 0.5-14.8) for females vs. males. Overall, 16.3% (95% CI 12.5-20.9) of
patients reported post-operative, non-positional headaches. CONCLUSIONS: There
was a low overall incidence of PDPH among patients aged 15-45. Pre-planned
subgroup analyses of PDPH incidence by age group revealed a high risk of PDPH
among a small sample of 15-19-year-olds.
PMID- 28690465
TI - Thrombotic and Infectious Morbidity Are Associated with Transfusion in Posterior
Spine Fusion.
AB - BACKGROUND: Although previous investigators have established an association
between blood transfusion and adverse outcomes, the relative frequency of
different morbid events and the association with transfusion dose are not well
understood. QUESTIONS/PURPOSES: The purpose of the study is to characterize the
relationship between blood transfusion and different types of morbidity after
posterior spine fusion. METHODS: We retrospectively analyzed electronic medical
records for 963 patients who underwent posterior spinal fusion surgery at a
single institution, of which 603 (62.6%) received an allogeneic blood
transfusion. Then, we assessed patient and surgical characteristics in a risk
adjusted fashion to identify various morbid event rates and independent
predictors in these adverse outcomes. RESULTS: Compared to the non-transfused
patients, transfused patients had a higher incidence of any morbid event (9.1 vs.
2.5%. P < 0.0001), thrombotic events (4.6 vs. 1.1%, P = 0.0025), and hospital
acquired infections (2.3 vs. 0.6%, P = 0.039). Renal, respiratory, and ischemic
morbidity occurred less frequently and were not more common in transfused
patients. Risk-adjusted analysis revealed a dose-response effect, whereby for
each unit of allogeneic blood transfused, the risks of any morbid event (OR
1.183; 95% CI 1.103-1.274; P < 0.0001), thrombotic complication (OR 1.104; 95% CI
1.032-1.194; P = 0.0035), and infectious complication (OR 1.182; 95% CI 1.077
1.332; P = 0.0002) were increased. CONCLUSION: Our data demonstrate risk-adjusted
and transfusion dose-related increases in perioperative morbidity, with
thrombotic and infectious events being the most common.
PMID- 28690466
TI - Propionibacterium acnes Host Inflammatory Response During Periprosthetic
Infection Is Joint Specific.
AB - BACKGROUND: Propionibacterium acnes (P. acnes) has become increasingly recognized
as a cause of periprosthetic joint infection (PJI). QUESTIONS/PURPOSES: It is not
currently known if the clinical presentation of P. acnes varies depending on the
joint being infected. METHODS: We retrospectively reviewed patients infected with
P. acnes after total hip, knee, and shoulder arthroplasty from two institutions.
Patients were classified as having a PJI based on the Musculoskeletal Infection
Society criteria and were excluded if they had a polymicrobial culture. Patient
demographics, preoperative laboratory values, and microbiology data were
analyzed. RESULTS: Eighteen knees, 12 hips, and 35 shoulders with a P. acnes PJI
were identified. Median ESR was significantly higher in the knee (38.0 mm/h, IQR
18.0-58.0) and hip (33.5 mm/h, IQR 15.3-60.0) groups compared to the shoulder
group (11.0 mm/h, IQR 4.5-30.5). C-reactive protein levels were higher in the
knee (2.0 mg/dl, IQR 1.3-8.9) and hip (2.4 mg/dl, IQR 0.8-4.9) groups compared to
the shoulder group (0.7 mg/dl, IQR 0.6-1.5). Median synovial fluid WBC was
significantly higher in the knee group than shoulder group (19,950 cells/mm3, IQR
482-60,063 vs 750 cells/mm3, IQR 0-2825, respectively). Peripheral blood WBC
levels were similar between groups, as was mean time of P. acnes growth in
culture. Clindamycin resistance was present in all groups. CONCLUSION: The manner
in which a patient with P. acnes PJI presents is joint specific. Inflammatory
markers were significantly higher in the knee and hip groups compared to the hip
and shoulder groups, and long hold anaerobic cultures up to 14 days are necessary
to accurately identify this organism.
PMID- 28690467
TI - Prophylactic Postoperative Antibiotics May Not Reduce Pin Site Infections After
External Fixation.
AB - BACKGROUND: Pin infection continues to be a nuisance when using definitive
external fixation. Prophylactic antibiotic treatment has been proposed in an
effort to decrease pin complications. QUESTIONS/PURPOSES: We performed a
prospective, randomized, single-blinded study to answer the following questions:
(1) what was the effect of a 10-day course of oral prophylactic antibiotics
administered immediately after external fixation surgery on the incidence of a
subsequent pin infection, (2) what was the effect on the severity of a subsequent
pin infection, and (3) what was the effect on the timing of a subsequent pin
infection? METHODS: Patients were randomized into antibiotic treatment and
control groups, and incidence, severity, and time of onset of pin infection were
recorded. RESULTS: The incidence of pin infection for the entire cohort during
the 90-day observation period was 46/58 (79%) without a statistically significant
difference (p = 0.106). There was no statistical difference found (p = 0.512) in
pin infection severity. There was no significant difference in the time of onset
of infection between the two groups from the date of surgery (p = 0.553).
CONCLUSIONS: Our randomized data do not suggest that oral antibiotics alter the
incidence, timing, or severity of pin infection. This study does not support the
use of prophylactic oral antibiotics in healthy patients.
PMID- 28690468
TI - Bone Mineral Density Response from Teriparatide in Patients with Osteoporosis.
AB - BACKGROUND: A review of data from large clinical trials reported more than 90% of
subjects significantly improved their bone mineral density (BMD) at the lumbar
spine (LS) with teriparatide (TPTD) (bone 39:1268-1275, 1). However, our clinical
experience suggests that many patients may be non-responders, raising questions
as to the true efficacy of TPTD in improving BMD in osteoporotic patients.
QUESTIONS/PURPOSES: The purpose of the study is to determine the rate of
improvement in BMD following 18-24 months of teriparatide (TPTD) in patients with
osteoporosis within an orthopedic hospital setting. METHODS: This is a
retrospective chart review of patients with osteoporosis who completed 18-24
months of TPTD therapy. The primary endpoint was the change in BMD at lumbar
spine (LS) and hip-femoral neck (FN) and total hip (TH) following treatment.
Secondary endpoints included the effect of prior bisphosphonate therapy, age,
body mass index (BMI) and family history of fracture on BMD response, and the
changes in bone-specific markers during active treatment. RESULTS: Seventy-eight
women and men with mean T-scores at the LS = -2.63 met the inclusion criteria.
The overall group showed a 10.7% increase in LS-BMD after 24 months of TPTD.
Eighty-three percent were considered responders defined as >=3.0% increase in LS
BMD. Non-responders (16.7%) had mean LS-BMD change = -1.41%. No difference in
baseline vitamin D, calcium, creatinine, BMI, age, gender, prior fracture
history, or bisphosphonate use was observed between responders and non
responders. No consistent pattern of change in measures of bone markers was noted
between responders and non-responders. CONCLUSION: Eighty-three percent of
patients with osteoporosis showed a >3% increase in BMD after TPTD treatment.
Baseline parameters, prior bisphosphonate therapy, and the changes in bone
markers showed no correlation with final BMD outcome.
PMID- 28690469
TI - Ankle Reconstruction in Fibular Hemimelia: New Approach.
AB - BACKGROUND: Fibular hemimelia is a congenital disorder that is characterized by
the absence of the fibula that could be either partial or complete. Successful
management aims to restore normal weight bearing and normal limb length. The
introduction of the Ilizarov method of limb lengthening has provided an
attractive alternative to amputation. During lengthening, the tight
posterolateral soft-tissue structures, the thick fibrous fibular band, and the
shortened Achilles tendon become tighter and transfer a valgus force to the talus
and calcaneus, further aggravating the deformity. QUESTIONS/PURPOSES: We have
developed a strategy to address this in patients with Paley type III fibular
hemimelia via ankle reconstruction that provides posterolateral stability and
buttressing of the ankle and hind foot by reconstructing the lateral buttress.
This is achieved through excision of the fibrous fibular anlage, centralization
of the ankle, restoring talocalcaneal coronal alignment, and reconstruction of
the lateral malleolus by transplanting the cartilaginous remnant of the lateral
malleolus or by crafting a bone block autograft taken from the iliac crest or
tibia. METHODS: A prospective non-randomized clinical trial included ten ankles
in eight patients with fibular hemimelia Paley type III (two patients had
bilateral deformity). The patients' ages ranged from 7 to 36 months. RESULTS:
After a follow-up ranging from 48 to 96 months, a stable plantigrade foot was
achieved in nine ankles; one ankle had residual equinus, five ankles had residual
valgus heel, and eight ankles had complete range of motion of the ankle, whereas
one patient lost 5 degrees of dorsiflexion. One ankle had equinus deformity.
CONCLUSIONS: To achieve satisfactory results, a stable plantigrade foot and ankle
is necessary in patients with fibular hemimelia before attempting to equalize
limb length discrepancy. It is important to reconstruct the ankle through an
extra-articular soft tissue release, anlage resection, osteotomies, and restoring
the abnormal talocalcaneal relationship before any attempt to equalize LLD.
PMID- 28690471
TI - Using Mobile Tracking Technology to Visualize the Trajectory of Recovery After
Hip Arthroscopy: a Case Report.
PMID- 28690470
TI - Equivalent Clinical Outcomes Following Favored Treatments of Chronic Scapholunate
Ligament Tear.
AB - BACKGROUND: Optimal treatment of chronic scapholunate (SL) instability remains
controversial. Many surgical techniques have been proposed with varied results in
subsequent case series; however, there is limited evidence demonstrating the
relative effectiveness of the different treatment options. QUESTIONS/PURPOSES: We
conducted a systematic review of the English literature to compare outcomes from
capsulodesis and ligament reconstruction for treatment of chronic scapholunate
instability. METHODS: An electronic database search using keywords associated
with scapholunate ligament instability was performed. A total of 511 studies were
identified. All studies with scapholunate ligament tears >4 weeks after the
initial injury were included in the review. Data extracted included patient
demographics, wrist range of motion, and radiographic outcome measures. RESULTS:
A total of 308 patients from 11 studies met the inclusion criteria and were
included in the study. The average time to surgery from initial injury was 11
months. There was no significant difference in wrist flexion or extension after
capsulodesis or reconstruction. The weighted mean for postoperative wrist
extension/flexion was 56 degrees /45.6 degrees in the capsulodesis group and
40.9 degrees /47.3 degrees in the reconstruction group. Pooled means of SL angle
and SL gap were 60.3 degrees and 3.44 mm after capsulodesis and 56.5 and 2.72 mm
after reconstruction, respectively. CONCLUSIONS: This systematic review failed to
demonstrate any significant difference in outcomes from capsulodesis or
reconstruction for treatment of chronic scapholunate instability. However, the
retrospective studies examined were notably heterogeneous in design with high
estimates of variance. Further prospective trials are necessary to determine an
ideal treatment strategy.
PMID- 28690472
TI - Lung Adenocarcinoma with Miliary Metastases and Left Femur Pathologic Fracture:
an Unusual Case Mimicking Disseminated Tuberculosis.
PMID- 28690474
TI - Design of nucleic acid strands with long low-barrier folding pathways.
AB - A major goal of natural computing is to design biomolecules, such as nucleic acid
sequences, that can be used to perform computations. We design sequences of
nucleic acids that are "guaranteed" to have long folding pathways relative to
their length. This particular sequences with high probability follow low-barrier
folding pathways that visit a large number of distinct structures. Long folding
pathways are interesting, because they demonstrate that natural computing can
potentially support long and complex computations. Formally, we provide the first
scalable designs of molecules whose low-barrier folding pathways, with respect to
a simple, stacked pair energy model, grow superlinearly with the molecule length,
but for which all significantly shorter alternative folding pathways have an
energy barrier that is [Formula: see text] times that of the low-barrier pathway
for any [Formula: see text] and a sufficiently long sequence.
PMID- 28690473
TI - Total Knee Arthroplasty for Knee Osteoarthritis: Support for a Foregone
Conclusion?
AB - Total knee arthroplasty (TKA) is generally accepted as the definitive treatment
for advanced knee arthritis after patients fail nonoperative treatments; however,
the safety and efficacy of TKA compared to continued nonoperative treatment has
never been proven in high-quality, randomized controlled trials. Recently, a 2015
Danish study published a 12-month follow-up on a cohort of patients randomized to
either a TKA or continued nonsurgical management for advanced knee osteoarthritis
(OA). The authors reported significantly greater improvement in the TKA group in
functional outcome scores such as the overall Knee Injury and Osteoarthritis
Outcome Score (KOOS4 score), the KOOS subscales, EQ-5D descriptive index, and
timed get up-and-go and 20-m walk tests; however, patients in the TKA did suffer
significantly more serious adverse events (SAE). The authors concluded that TKA
combined with additional nonoperative care postoperatively is more efficacious
than nonsurgical treatment alone in terms of improving pain, function, and
quality of life at 12 months but is associated with more SAE. The purpose of this
review is to identify the strengths and weaknesses of this trial, interpret its
outcomes within the context of prior literature, and evaluate the validity of its
conclusions.
PMID- 28690475
TI - Modified local sands for the mitigation of harmful algal blooms.
AB - A new method was developed for marine harmful algal bloom (HAB) mitigation using
local beach sand or silica sand modified with chitosan and polyaluminum chloride
(PAC). Untreated sand was ineffective in flocculating algal cells, but 80%
removal efficiency was achieved for Amphidinium carterae Hulburt and a Chlorella
sp. in 3 min (t80 = 3 min) using 120 mg L-1 sand modified with 10 mg L-1 PAC and
10 mg L-1 chitosan. After several hours 92% - 96% removal was achieved. The t80
for removing A. carterae using the modifiers only (PAC and chitosan combined) was
60 min and for Chlorella sp. 120 min, times which are much slower than with the
corresponding modified sand. Sands were critical for speeding up the kinetic
processes of flocculation and sedimentation of algal flocs. PAC was helpful in
forming small flocs and chitosan is essential to bridge the small flocs into
large dense flocs. Chitosan was also important in inhibiting the escape of cells
from the flocs. Chitosan and PAC used together as modifiers make it possible to
use local beach sands for HAB mitigation in seawater. Economical and
environmental concerns could be reduced through the use of sands and
biodegradable chitosan, but the potential impacts of PAC need further study.
PMID- 28690476
TI - Dynamics of Alexandrium fundyense blooms and shellfish toxicity in the Nauset
Marsh System of Cape Cod (Massachusetts, USA).
AB - Paralytic Shellfish Poisoning (PSP) toxins are annually recurrent along the
Massachusetts coastline (USA), which includes many small embayments and salt
ponds. Among these is the Nauset Marsh System (NMS), which has a long history of
PSP toxicity. Little is known, however, about the bloom dynamics of the causative
organism Alexandrium fundyense within that economically and socially important
system. The overall goal of this work was to characterize the distribution and
dynamics of A. fundyense blooms within the NMS and adjacent coastal waters by
documenting the distribution and abundance of resting cysts and vegetative cells.
Cysts were found predominantly in three drowned kettle holes or salt ponds at the
distal ends of the NMS - Salt Pond, Mill Pond, and Town Cove. The central region
of the NMS had a much lower concentration of cysts. Two types of A. fundyense
blooms were observed. One originated entirely within the estuary, seeded by cysts
in the three seedbeds. These blooms developed independently of each other and of
the A. fundyense population observed in adjacent coastal waters outside the NMS.
The temporal development of the blooms was different in the three salt ponds,
with initiation differing by as much as 30 days. These differences do not appear
to reflect the initial cyst abundances in these locations, and may simply result
from higher cell retention and higher nutrient concentrations in Mill Pond, the
first site to bloom. Germination of cysts accounted for a small percentage of the
peak cell densities in the ponds, so population size was influenced more by the
factors affecting growth than by cyst abundance. Subsurface cell aggregation
(surface avoidance) limited advection of the vegetative A. fundyense cells out of
the salt ponds through the shallow inlet channels. Thus, the upper reaches of the
NMS are at the greatest risk for PSP since the highest cyst abundances and cell
concentrations were found there. After these localized blooms in the salt ponds
peaked and declined, a second, late season bloom occurred within the central
portions of the NMS. The timing of this second bloom relative to those within the
salt ponds and the coastal circulation patterns at that time strongly suggest
that those cells originated from a regional A. fundyense bloom in the Gulf of
Maine, delivered to the central marsh from coastal waters outside the NMS through
Nauset Inlet. These results will guide policy decisions about water quality as
well as shellfish monitoring and utilization within the NMS and highlight the
potential for "surgical" closures of shellfish during PSP events, leaving some
areas open for harvesting while others are closed.
PMID- 28690477
TI - Identity-by-descent refines mapping of candidate regions for preaxial polydactyly
II /III in a large Chinese pedigree.
AB - Preaxial polydactyly (PPD) is congenital hand malformation characterized by the
duplication of digit. Herein, we scan the genome-wide SNPs for a large Chinese
family with PPD-II/III. We employ the refined IBD algorithm to identify the
identity-by-decent (IBD) segments and compare the frequency among the patients
and normal relatives. A total of 72 markers of 0.01 percentile of the permutation
are identified as the peak signals. Among of them, 57markers locate on chromosome
7q36 which is associated with PPD. Further analyses refine the mapping of
candidate region in chromosome 7q36 into two 380 Kb fragments within LMBR1 and
SHH respectively. IBD approach is a suitable method for mapping causal gene of
human disease. Target-enrichment sequencing as well as functional experiments are
required to illustrate the pathogenic mechanisms for PPD in the future.
PMID- 28690478
TI - Genetic diversity and structure of core collection of winter mushroom (Flammulina
velutipes) developed by genomic SSR markers.
AB - BACKGROUND: A core collection is a subset of an entire collection that represents
as much of the genetic diversity of the entire collection as possible. The
establishment of a core collection for crops is practical for efficient
management and use of germplasm. However, the establishment of a core collection
of mushrooms is still in its infancy, and no established core collection of the
economically important species Flammulina velutipes has been reported. RESULTS:
We established the first core collection of F. velutipes, containing 32 strains
based on 81 genetically different F. veltuipes strains. The allele retention
proportion of the core collection for the entire collection was 100%. Moreover,
the genetic diversity parameters (the effective number of alleles, Nei's expected
heterozygosity, the number of observed heterozygosity, and Shannon's information
index) of the core collection showed no significant differences from the entire
collection (p > 0.01). Thus, the core collection is representative of the genetic
diversity of the entire collection. Genetic structure analyses of the core
collection revealed that the 32 strains could be clustered into 6 groups, among
which groups 1 to 3 were cultivars and groups 4 to 6 were wild strains. The wild
strains from different locations harbor their own specific alleles, and were
clustered stringently in accordance with their geographic origins. Genetic
diversity analyses of the core collection revealed that the wild strains
possessed greater genetic diversity than the cultivars. CONCLUSION: We
established the first core collection of F. velutipes in China, which is an
important platform for efficient breeding of this mushroom in the future. In
addition, the wild strains in the core collection possess favorable agronomic
characters and produce unique bioactive compounds, adding value to the platform.
More attention should be paid to wild strains in further strain breeding.
PMID- 28690479
TI - Microarray study of gene expression profile to identify new candidate genes
involved in the molecular mechanism of leptin-induced knee joint osteoarthritis
in rat.
AB - BACKGROUND: Osteoarthritis (OA) is one of the most prevalent chronic joint
diseases while the precise genetic mechanism remains elusive. In this study, we
investigated the gene expression profile in OA by microarray analysis. RESULTS:
Histopathological characteristics of OA cartilage were examined using a rat model
of leptin-induced OA. Gene expression profile of leptin-induced articular
cartilage and healthy rat cartilage were compared using genome-wide microarray
hybridization. A total of 1857 genes differentially expressed genes (1197
upregulated and 660 downregulated) were identified, some of which are known to be
associated with leptin-induced OA phenotype. These included genes related to
MMPs, inflammatory factors, growth factors, apoptotic genes and osteogenic genes.
In addition, upregulated expressions of some new candidate genes, which have
hitherto fore not been linked to OA (such as BCL2L11) were detected in leptin
induced OA cartilage, which suggests that these genes might be important for OA
molecular mechanism. CONCLUSION: Our findings suggest that pathogenesis of leptin
induced OA involves modulation of expression of multiple genes, although the
underlying molecular mechanisms need to be studied further. Further investigation
of leptin-induced gene expression changes is needed to gain new insights into the
molecular mechanism of OA pathogenesis.
PMID- 28690480
TI - The use of planned behavior theory in predicting cigarette smoking among
Waterpipe smokers.
AB - BACKGROUND: Waterpipe and cigarette smoking have been found to be associated with
each other as cigarette smokers were more likely to be waterpipe users than non
cigarette smokers. Also, waterpipe smokers were likely to be former daily
cigarette users. The aim of this study is to examine the likelihood of waterpipe
use leading to cigarette use among current waterpipe users using theory of
planned behavior. METHODS: Four hundred six current waterpipe smokers who
initially had started tobacco use with the waterpipe were recruited from 15
waterpipe lounges in 2015. From a total of 70 waterpipe lounges in Riyadh, the 15
waterpipe lounges were selected randomly and participants were also selected
randomly inside each waterpipe lounge based on the table or section number. The
survey was developed using the Qualtrics Online Survey Software and participants
completed a survey using iPad tablets. RESULTS: Cigarette smoking and intention
to smoke cigarettes were predicted by attitude and perceived behavioral control.
There was no direct effect of subjective norm on the cigarette use behavior, yet
subjective norm had a statistically significant indirect effect on intentions
through attitude and perceived behavioral control. CONCLUSIONS: The findings of
this study could be useful in prevention/intervention programs aimed at reducing
tobacco smoking behaviors among waterpipe users. Intervention programs might be
directed at the attitude and perceived behavioral control by targeting underlying
behavioral and control beliefs. The theory of planned behavior provided solid
explanations of intention to use cigarettes among waterpipe smokers.
PMID- 28690481
TI - The Age of the Father.
PMID- 28690482
TI - Barber-Say Syndrome and Ablepharon-Macrostomia Syndrome: A Patient's View.
AB - Barber-Say syndrome (BSS) and ablepharon-macrostomia syndrome (AMS) are
infrequently reported congenital malformation disorders caused by mutations in
the TWIST2 gene. Both are characterized by abnormalities in ectoderm-derived
structures and cause a very unusual morphology of mainly the face in individuals
with otherwise normal cognition and normal physical functioning. We studied the
impact that the presence of BSS and AMS has on psychosocial functioning of
affected individuals and their families, using their point of view to start with.
We tabulated frequently asked questions from affected individuals and families,
and a parent of an affected child and an affected adult woman offered personal
testimonies. We focused on perception of illness, body satisfaction, and the
consequences for an otherwise normal individual who has a disorder that
interferes with body image. The importance of paying particular attention to the
management of both the physical appearance and the consequences of these entities
on the quality of life is stressed by the affected individuals themselves.
PMID- 28690483
TI - Novel Mutations in the Crystallin Gene in Age-Related Cataract Patients from a
North Indian Population.
AB - Cataract is the most prevalent leading cause of visual impairment and blindness
worldwide. In comparison to congenital cataract, which affects relatively few
individuals, age-related cataract is responsible for slightly half of all cases
of blindness worldwide. Although significant work has been done, the genetic
aspect of age-related cataract is still in its infancy. The current study was
performed to analyze the mutations and polymorphisms in the CRYAA, CRYAB, CRYBB1,
and GJA8 genes in 40 unrelated age-related cataract patients. Mutational analysis
of the above-mentioned genes in 40 cataract cases revealed 14 different
substitutions of which 8 variants were novel and 6 were reported SNPs. Two
disease-causing mutations, g.44590631G>A (p.R65Q) and g.44592224G>A (p.R119H),
were also observed in the CRYAA gene. The disease-causing variants mildly affect
the stability, functionality, and localization of crystallin, and, with
progressing age, a small change in the microenvironment of the crystallin lens
occurs. This change in combination with a mutation may significantly alter the
functionality of the crystallin protein, leading to age-related cataract.
PMID- 28690484
TI - Genomic Investigation of Balanced Chromosomal Rearrangements in Patients with
Abnormal Phenotypes.
AB - Balanced chromosomal rearrangements (BCR) are associated with abnormal phenotypes
in approximately 6% of balanced translocations and 9.4% of balanced inversions.
Abnormal phenotypes can be caused by disruption of genes at the breakpoints,
deletions, or positional effects. Conventional cytogenetic techniques have a
limited resolution and do not enable a thorough genetic investigation. Molecular
techniques applied to BCR carriers can contribute to the characterization of this
type of chromosomal rearrangement and to the phenotype-genotype correlation.
Fifteen individuals among 35 with abnormal phenotypes and BCR were selected for
further investigation by molecular techniques. Chromosomal rearrangements
involved 11 reciprocal translocations, 3 inversions, and 1 balanced insertion.
Array genomic hybridization (AGH) was performed and genomic imbalances were
detected in 20% of the cases, 1 at a rearrangement breakpoint and 2 further
breakpoints in other chromosomes. Alterations were further confirmed by FISH and
associated with the phenotype of the carriers. In the analyzed cases not showing
genomic imbalances by AGH, next-generation sequencing (NGS), using whole genome
libraries, prepared following the Illumina TruSeq DNA PCR-Free protocol
(Illumina(r)) and then sequenced on an Illumina HiSEQ 2000 as 150-bp paired-end
reads, was done. The NGS results suggested breakpoints in 7 cases that were
similar or near those estimated by karyotyping. The genes overlapping 6
breakpoint regions were analyzed. Follow-up of BCR carriers would improve the
knowledge about these chromosomal rearrangements and their consequences.
PMID- 28690486
TI - ADULT Phenotype and rs16864880 in the TP63 Gene: Two New Cases and Review of the
Literature.
AB - The TP63 gene has been described in 5 overlapping limb malformation disorders,
including a rare autosomal dominant ectodermal disorder named acro-dermato-ungual
lacrimal-tooth (ADULT) syndrome. This article describes 2 patients with
ectrodactyly and variable features related to ectodermal dysplasia/ADULT
syndrome, and the polymorphism rs16864880 in the TP63 gene, which was not present
in their parents. The role of this variant in the genesis of this condition is
discussed, based upon a review of 40 cases. The results suggested that rs16864880
may not be directly related to ADULT syndrome. However, it is not possible to
exclude its participation in gene interactions in the limb development pathway.
PMID- 28690485
TI - A Novel Pathogenic Variant in the MITF Gene Segregating with a Unique Spectrum of
Ocular Findings in an Extended Iranian Waardenburg Syndrome Kindred.
AB - Waardenburg syndrome (WS) is a rare genetic disorder characterized by abnormal
pigmentation of the hair, skin, and iris as well as sensorineural hearing loss.
WS is subdivided into 4 major types (WS1-4), where WS2 is characterized by the
absence of dystopia canthorum. This study was launched to investigate clinical
and molecular characteristics of WS in an extended Iranian WS2 family. A
comprehensive clinical investigation was performed. Peripheral blood samples were
collected and genomic DNA was extracted. Affected members of the family were
studied for possible mutations within the SOX10, MITF, and SNAI2 genes. Six WS2
individuals affected from a large Iranian WS2 kindred were enrolled. All affected
members carried the novel substitution c.877C>T at exon 9 in the MITF gene, which
resulted in p.Arg293* at the protein level. None of the healthy members and also
of 50 ethnically matched controls had this variant. In addition, a spectrum of
unique ocular findings, including nystagmus, chorioretinal degeneration, optic
disc hypoplasia, astigmatism, and myopia, was segregated with the mutant allele
in the pedigree. Our data provide insight into the genotypic and phenotypic
spectrum of WS2 in an Iranian family and could further expand the spectrum of
MITF mutations and have implications for genetic counseling on WS in Iran.
PMID- 28690487
TI - Cantu Syndrome Associated with Ovarian Agenesis.
AB - Cantu syndrome is a very rare autosomal dominant disorder characterized by
generalized congenital hypertrichosis, neonatal macrosomia, coarse face,
cardiomegaly, and occasionally, skeletal abnormalities. The syndrome has been
attributed to mutated ABCC9 or KCNJ8 genes. We present a 4-year-old girl with
developmental delay, distinctive coarse facial features, and generalized
hypertrichosis apparent since birth. The investigation revealed absent ovaries
and a hypoplastic uterus which have not been previously described. Conventional
karyotyping was normal. DNA sequencing analysis of the ABCC9 gene was performed,
and a heterozygous point mutation c.3460C>T (p.Arg1154Trp) was revealed. This
missense gain-of-function mutation was located in exon 27 of the ABCC9 gene and
has been reported in patients with the full phenotype of Cantu syndrome. However,
the absence of the ovaries could be an expansion of the phenotype and not
attributed to mutations in other genes important for ovarian development.
Unfortunately, it has not been proven so far if the ABCC9 gene is expressed in
the ovarian tissue.
PMID- 28690489
TI - Severe Neurological Phenotype in a Girl with Xp22.31 Triplication.
AB - The Xp22.31 duplication is a copy number variant which is challenging to
categorize as pathogenic or benign. There is an increasing number of patients
with the duplication and a neurobehavioral phenotype, but the duplication is
almost always inherited from a parent, who in some cases is phenotypically
normal. Also, the duplication is detected in the general population, though in a
smaller percentage than in clinically ascertained populations. The Xp22.31
triplication has only been identified in 3 individuals of a large cohort of
developmental delay cases but never in the control cohorts or general population.
We report a severely affected female with an Xp22.31 tetrasomy, inherited from
duplications identified in both phenotypically normal parents. Although our study
has limitations, it suggests that the Xp22.31 triplication seems to be more
penetrant than the duplication and is associated with a neurological phenotype.
PMID- 28690488
TI - A Novel Partial Duplication of ZEB2 and Review of ZEB2 Involvement in Mowat
Wilson Syndrome.
AB - Mowat-Wilson syndrome is a rare genetic condition characterized by intellectual
disability, structural anomalies, and dysmorphic features. It is caused by
haploinsufficiency of the ZEB2 gene in chromosome 2q22.3. Over 180 distinct
mutations in ZEB2 have been reported, including nonsense and missense point
mutations, deletions, and large chromosomal rearrangements. We report on a 14
year-old female with a clinical diagnosis of Mowat-Wilson syndrome. Chromosomal
microarray identified a novel de novo 69-kb duplication containing exons 1 and 2
of the ZEB2 gene. Sequence analysis identified no other variants in this gene.
This is the first report of a partial duplication of the ZEB2 gene resulting in
Mowat-Wilson syndrome.
PMID- 28690490
TI - A Hepatitis C Virus-Associated Cirrhotic Patient Developing Interstitial
Pneumonia during the Course of Antiviral Therapy with
Ombitasvir/Paritaprevir/Ritonavir.
AB - Oral direct-acting antivirals (DAAs) are the main therapy for hepatitis C virus
(HCV)-associated liver disease in Japan. Daclatasvir/asunaprevir is the first
agent and sofosbuvir/ledipasvir is the secondary agent for HCV genotype 1b. More
recently, ombitasvir/paritaprevir/ritonavir is also recommended as a potent
therapy for HCV genotype 1b. Among the adverse events associated with these oral
DAAs, interstitial pneumonia is one of the most severe ones. Regarding treatment
with daclatasvir plus asunaprevir or sofosbuvir plus ledipasvir, a few cases have
already been reported in a postmarketing surveillance. Recently, we have
encountered a HCV-associated genotype 1b cirrhosis patient who developed
interstitial pneumonia during treatment with ombitasvir/paritaprevir/ritonavir
and who recovered after drug discontinuation without corticosteroid therapy.
Interstitial pneumonia was confirmed by chest x-ray and chest computed
tomography. The serum KL-6 level was elevated to 1,180 U/mL. The total duration
of the drug administration was 7 weeks, and she achieved SVR24. This is the first
detailed report in the literature on the development of interstitial pneumonia
during treatment with ombitasvir/paritaprevir/ritonavir. When dry cough appeared
in the treatment with DAAs, chest computed tomography and the evaluation of serum
KL-6 level were recommended.
PMID- 28690491
TI - A Complicated Thread: Abdominal Actinomycosis in a Young Woman with Crohn
Disease.
AB - Crohn disease is a chronic inflammatory condition that primarily affects the
gastrointestinal tract. Typical manifestations include fever, weight loss,
fatigue, and abdominal pain, and abdominal abscesses and fistulae are frequent
complications. Abdominal actinomycosis is a subacute or indolent disease
associated with Actinomyces spp. Symptoms can be very similar to those of Crohn
disease, and fistulae are also common. Since ulcerations in the intestinal tract
are thought to be caused by Actinomyces escaping from the gut lumen and
establishing intra-abdominal infection, it seems likely that abdominal
actinomycosis may occur in patients with inflammatory bowel disease. We report a
case of abdominal actinomycosis in a woman with active Crohn disease.
PMID- 28690492
TI - Interval Squamous Cell Carcinoma of the Rectum.
AB - Squamous cell carcinoma (SCC) of the rectum is a rare clinical entity with an
incidence rate of 0.1-0.25% per 1,000 cases. Though its etiology and pathogenesis
remains unclear, it has been associated with chronic inflammation and infections.
Herein, we report a case of an 82-year-old female who presented with a 2-month
history of worsening abdominal pain, hematochezia, and bilateral inguinal
lymphadenopathy with right-sided purulent discharge. Two years prior, she had had
an unremarkable screening colonoscopy which met all quality indicators. Abdominal
CT scan showed an irregular rectal mass with bulky pelvic and retroperitoneal
adenopathy. Colonoscopy revealed one large circumferential nonobstructing lesion
in the rectum. Endoscopic ultrasound confirmed its origin from the rectal wall
with an enlarged perirectal lymph node. Cold biopsy followed by histopathology
revealed SCC of the rectum.
PMID- 28690493
TI - Emerging Signaling Pathway in Arcuate Feeding-Related Neurons: Role of the Acbd7.
AB - The understanding of the mechanisms whereby energy balance is regulated is
essential to the unraveling of the pathophysiology of obesity. In the last three
decades, focus was put on the metabolic role played by the hypothalamic neurons
expressing proopiomelanocortin (POMC) and cocaine and amphetamine regulated
transcript (CART) and the neurons co-localizing agouti-related peptide (AgRP),
neuropeptide Y (NPY), and gamma-aminobutyric acid (GABA). These neurons are part
of the leptin-melanocortin pathway, whose role is key in energy balance
regulation. More recently, the metabolic involvement of further hypothalamic
uncharacterized neuron populations has been suggested. In this review, we discuss
the potential homeostatic implication of hypothalamic GABAergic neurons that
produce Acyl-Coa-binding domain containing protein 7 (ACBD7), precursor of the
nonadecaneuropeptide (NDN), which has recently been characterized as a potent
anorexigenic neuropeptide capable of relaying the leptin anorectic/thermogenic
effect via the melanocortin system.
PMID- 28690495
TI - Cognitive Challenge to Choose Healthier Food Is Reflected in Heart Rate
Variability.
PMID- 28690494
TI - The Electrically Evoked Compound Action Potential: From Laboratory to Clinic.
AB - The electrically evoked compound action potential (eCAP) represents the
synchronous firing of a population of electrically stimulated auditory nerve
fibers. It can be directly recorded on a surgically exposed nerve trunk in
animals or from an intra-cochlear electrode of a cochlear implant. In the past
two decades, the eCAP has been widely recorded in both animals and clinical
patient populations using different testing paradigms. This paper provides an
overview of recording methodologies and response characteristics of the eCAP, as
well as its potential applications in research and clinical situations. Relevant
studies are reviewed and implications for clinicians are discussed.
PMID- 28690496
TI - Dynamic Changes in the Renin-Angiotensin-Aldosterone System and the Beneficial
Effects of Renin-Angiotensin-Aldosterone Inhibitors on Spatial Learning and
Memory in a Rat Model of Chronic Cerebral Ischemia.
AB - Renin-angiotensin-aldosterone system (RAAS) plays an important role in the
regulation of blood pressure and brain function. Therefore, we studied the
dynamic changes in the RAAS in the blood, cerebral cortex, and hippocampus and
the effects of RAAS inhibitors on spatial learning and memory and hippocampal
apoptosis in a rat model of chronic cerebral ischemia (CCI) established by
bilateral ligation of the common carotid arteries of rats. The levels of renin,
angiotensin II (Ang II), and aldosterone (ALD) in the plasma, and the homogenates
of the left side of cerebral cortex and whole hippocampus of rats were detected
on day 1, 3, 7, 14, 21, and 30 by radioimmunoassay. Spatial learning and memory
and hippocampal apoptosis were evaluated on day 30 by Morris water maze test
(navigation and space exploration tests) and terminal dexynucleotidyl transferase
(TdT)-mediated dUTP nick end labeling (TUNEL) assay, respectively, after rats
were orally administered with distilled water (DW), renin inhibitor aliskiren (30
mg/kg), Ang converting enzyme inhibitor enalapril (4 mg/kg), or Ang II receptor
antagonist candesartan (2 mg/kg) daily for 30 days. The results showed that the
levels of renin and Ang II were significantly higher but ALD fluctuated in the
blood, cerebral cortex, and hippocampus in CCI rats compared to normal rats.
However, aliskiren and enalapril could significantly decrease (p < 0.05) the
levels of renin, Ang II and ALD in the blood, cerebral cortex, and hippocampus
compared to DW treatment; while candesartan had similar effect on renin and ALD
but no effect on Ang II in CCI rats. Furthermore, spatial learning and memory
were significantly decreased but apoptosis in the hippocampus was obviously
increased in CCI rats compared to normal rats (p < 0.05). However, aliskiren,
enalapril, and candesartan were equally effective to improve spatial learning and
memory and decrease apoptosis in the hippocampus. Therefore, RAAS plays an
important role in the development of cerebral ischemia and RAAS inhibitors
aliskiren, enalapril, and candesartan improve spatial learning and memory and
protect brain injury by inhibiting hippocampal apoptosis in CCI rats.
PMID- 28690497
TI - High Amplitude EEG Motor Potential during Repetitive Foot Movement: Possible Use
and Challenges for Futuristic BCIs That Restore Mobility after Spinal Cord
Injury.
AB - Recent advances in neuroprostheses provide us with promising ideas of how to
improve the quality of life in people suffering from impaired motor functioning
of upper and lower limbs. Especially for patients after spinal cord injury (SCI),
futuristic devices that are controlled by thought via brain-computer interfaces
(BCIs) might be of tremendous help in managing daily tasks and restoring at least
some mobility. However, there are certain problems arising when trying to
implement BCI technology especially in such a heterogenous patient group. A
plethora of processes occurring after the injuries change the brain's structure
as well as its functionality collectively referred to as neuroplasticity. These
changes are very different between individuals, leading to an increasing interest
to reveal the exact changes occurring after SCI. In this study we investigated
event-related potentials (ERPs) derived from electroencephalography (EEG) signals
recorded during the (attempted) execution and imagination of hand and foot
movements in healthy subjects and patients with SCI. As ERPs and especially early
components are of interest for BCI research we aimed to investigate differences
between 22 healthy volunteers and 7 patients (mean age = 51.86, SD = 15.49)
suffering from traumatic or non-traumatic SCI since 2-314 months (mean = 116,57,
SD = 125,55). We aimed to explore differences in ERP responses as well as the
general presence of component that might be of interest to further consider for
incorporation into BCI research. In order to match the real-life situation of
BCIs for controlling neuroprostheses, we worked on small trial numbers (<25),
only. We obtained a focal potential over Pz in ten healthy participants but in
none of the patients after lenient artifact rejection. The potential was
characterized by a high amplitude, it correlated with the repeated movements (6
times in 6 s) and in nine subjects it significantly differed from a resting
condition. Furthermore, there are strong arguments against possible confounding
factors leading to the potential's appearance. This phenomenon, occurring when
movements are repeatedly conducted, might represent a possible potential to be
used in futuristic BCIs and further studies should try to investigate the
replicability of its appearance.
PMID- 28690498
TI - Amyloid-precursor Like Proteins APLP1 and APLP2 Are Dispensable for Normal
Development of the Neonatal Respiratory Network.
AB - Recent studies using animal models indicated that the members of the amyloid
precursor protein (APP) gene family are important for the formation, maintenance,
and plasticity of synapses. Despite this, the specific role of the APP homologs
APLP1 and APLP2 within the CNS and PNS is still poorly understood. In contrast to
the subtle phenotypes of single mutants, double knockout mice (DKO) lacking
APP/APLP2 or APLP1/APLP2 die within the first day after birth. Whereas APP/APLP2
DKO mice show severe deficits of neuromuscular morphology and transmission, the
underlying cause of lethality of APLP1/APLP2-DKO mice remains unclear. Since
expression of both proteins was confirmed by in situ hybridization, we aimed to
test the role of APLP1/APLP2 in the formation and maintenance of synapses in the
brainstem, and assessed a potential dysfunction of the most vital central
neuronal network in APLP1/APLP2-DKO mice by analyzing the respiratory network of
the medulla. We performed in vivo unrestrained whole body plethysmography in
newborn APLP1/APLP2-DKO mice at postnatal day zero. Additionally, we directly
tested the activity of the respiratory network in an acute slice preparation that
includes the pre-Botzinger complex. In both sets of experiments, no significant
differences were detected regarding respiratory rate and cycle variability,
strongly arguing against central respiratory problems as the primary cause of
death of APLP1/APLP2-DKO mice. Thus, we conclude that APLP1 and APLP2 are
dispensable for the development of the network and the generation of a normal
breathing rhythm.
PMID- 28690499
TI - Reduced Circulating Levels of miR-433 and miR-133b Are Potential Biomarkers for
Parkinson's Disease.
AB - Aberrant expression of microRNA (miRNA) in tissues may lead to altered level in
circulation. Considerable evidence has suggested that miRNA deregulation is
involved in the pathogenesis of Parkinson's disease (PD). In this study, we
screened a set of PD-associated miRNAs and aimed to identify differentially
expressed miRNAs in plasma of PD patients and to evaluate their potentiality to
serve as PD biomarkers. A total of 95 subjects consisting of 46 sporadic PD cases
and 49 controls were recruited. Plasma levels of six miRNAs including miR-433,
miR-133b, miR-34b, miR-34c, miR-153, and miR-7 were evaluated using reverse
transcribed quantitative PCR, among which we found that miR-34c and miR-7 were
below detection limit under our condition. The results showed that levels of
circulating miR-433 (P = 0.003) and miR-133b (P = 0.006), but not miR-34b and miR
153, were reduced in PD patients. miR-433 and miR-133b were strongly correlated
in both control and PD groups (rs = 0.87 and 0.85, respectively). The correlation
between miR-34b and miR-153 expressions was significantly reduced (P < 0.05) in
the PD group. Although miR-433 and miR-133b were likely to be functionally
complimentary as suggested by Pathway and Gene Ontology analyses, these two
miRNAs per se might not be sufficient to predict PD. No correlation was observed
between the four miRNAs and age or severity of disease. Collectively, our results
demonstrate that circulating miR-433 and miR-133b are significantly altered in PD
and may serve as PD biomarkers.
PMID- 28690500
TI - Dysregulation of Microtubule Stability Impairs Morphofunctional Connectivity in
Primary Neuronal Networks.
AB - Functionally related neurons assemble into connected networks that process and
transmit electrochemical information. To do this in a coordinated manner, the
number and strength of synaptic connections is tightly regulated. Synapse
function relies on the microtubule (MT) cytoskeleton, the dynamics of which are
in turn controlled by a plethora of MT-associated proteins, including the MT
stabilizing protein Tau. Although mutations in the Tau-encoding MAPT gene
underlie a set of neurodegenerative disorders, termed tauopathies, the exact
contribution of MT dynamics and the perturbation thereof to neuronal network
connectivity has not yet been scrutinized. Therefore, we investigated the impact
of targeted perturbations of MT stability on morphological (e.g., neurite- and
synapse density) and functional (e.g., synchronous calcium bursting) correlates
of connectivity in networks of primary hippocampal neurons. We found that
treatment with MT-stabilizing or -destabilizing compounds impaired
morphofunctional connectivity in a reversible manner. We also discovered that
overexpression of MAPT induced significant connectivity defects, which were
accompanied by alterations in MT dynamics and increased resistance to
pharmacological MT depolymerization. Overexpression of a MAPT variant harboring
the P301L point mutation in the MT-binding domain did far less, directly linking
neuronal connectivity with Tau's MT binding affinity. Our results show that MT
stability is a vulnerable node in tauopathies and that its precise
pharmacological tuning may positively affect neuronal network connectivity.
However, a critical balance in MT turnover causes it to be a difficult
therapeutic target with a narrow operating window.
PMID- 28690502
TI - Serotonin 5-HTTLPR Genotype Modulates Reactive Visual Scanning of Social and Non
social Affective Stimuli in Young Children.
AB - Previous studies have documented the 5-HTTLPR polymorphisms as genetic variants
that are involved in serotonin availability and also associated with emotion
regulation and facial emotion processing. In particular, neuroimaging and
behavioral studies of healthy populations have produced evidence to suggest that
carriers of the Short allele exhibit heightened neurophysiological and behavioral
reactivity when processing aversive stimuli, particularly in brain regions
involved in fear. However, an additional distinction has emerged in the field,
which highlights particular types of fearful information, i.e., aversive
information which involves a social component versus non-social aversive stimuli.
Although processing of each of these stimulus types (social and non-social) is
believed to involve a subcortical neural system which includes the amygdala,
evidence also suggests that the amygdala itself may be particularly responsive to
socially significant environmental information, potentially due to the critical
relevance of social information for humans. Examining individual differences in
neurotransmitter systems which operate within this subcortical network, and in
particular the serotonin system, may be critically informative for furthering our
understanding of the neurobiological mechanisms underlying responses to emotional
and affective stimuli. In the present study we examine visual scanning patterns
in response to both aversive and positive images of a social or non-social nature
in relation to 5-HTTLPR genotypes, in 49 children aged 4-7 years. Results
indicate that children with at least one Short 5-HTTLPR allele spent less time
fixating the threat-related non-social stimuli, compared with participants with
two copies of the Long allele. Interestingly, a separate set of analyses suggests
that carriers of two copies of the short 5-HTTLPR allele also spent less time
fixating both the negative and positive non-social stimuli. Together, these
findings support the hypothesis that genetically mediated differences in
serotonin availability mediate behavioral responses to different types of
emotional stimuli in young children.
PMID- 28690501
TI - Cortical Activation during Landmark-Centered vs. Gaze-Centered Memory of Saccade
Targets in the Human: An FMRI Study.
AB - A remembered saccade target could be encoded in egocentric coordinates such as
gaze-centered, or relative to some external allocentric landmark that is
independent of the target or gaze (landmark-centered). In comparison to
egocentric mechanisms, very little is known about such a landmark-centered
representation. Here, we used an event-related fMRI design to identify brain
areas supporting these two types of spatial coding (i.e., landmark-centered vs.
gaze-centered) for target memory during the Delay phase where only target
location, not saccade direction, was specified. The paradigm included three tasks
with identical display of visual stimuli but different auditory instructions:
Landmark Saccade (remember target location relative to a visual landmark,
independent of gaze), Control Saccade (remember original target location relative
to gaze fixation, independent of the landmark), and a non-spatial control, Color
Report (report target color). During the Delay phase, the Control and Landmark
Saccade tasks activated overlapping areas in posterior parietal cortex (PPC) and
frontal cortex as compared to the color control, but with higher activation in
PPC for target coding in the Control Saccade task and higher activation in
temporal and occipital cortex for target coding in Landmark Saccade task. Gaze
centered directional selectivity was observed in superior occipital gyrus and
inferior occipital gyrus, whereas landmark-centered directional selectivity was
observed in precuneus and midposterior intraparietal sulcus. During the Response
phase after saccade direction was specified, the parietofrontal network in the
left hemisphere showed higher activation for rightward than leftward saccades.
Our results suggest that cortical activation for coding saccade target direction
relative to a visual landmark differs from gaze-centered directional selectivity
for target memory, from the mechanisms for other types of allocentric tasks, and
from the directionally selective mechanisms for saccade planning and execution.
PMID- 28690503
TI - Genetics of Schizophrenia: Overview of Methods, Findings and Limitations.
AB - Genetics constitute a crucial risk factor to schizophrenia. In the last decade,
molecular genetic research has produced novel findings, infusing optimism about
discovering the biological roots of schizophrenia. However, the complexity of the
object of inquiry makes it almost impossible for non-specialists in genetics
(e.g., many clinicians and researchers) to get a proper understanding and
appreciation of the genetic findings and their limitations. This study aims at
facilitating such an understanding by providing a brief overview of some of the
central methods and findings in schizophrenia genetics, from its historical
origins to its current status, and also by addressing some limitations and
challenges that confront this field of research. In short, the genetic
architecture of schizophrenia has proven to be highly complex, heterogeneous and
polygenic. The disease risk is constituted by numerous common genetic variants of
only very small individual effect and by rare, highly penetrant genetic variants
of larger effects. In spite of recent advances in molecular genetics, our
knowledge of the etiopathogenesis of schizophrenia and the genotype-environment
interactions remain limited.
PMID- 28690504
TI - Multiple Coordinate Systems and Motor Strategies for Reaching Movements When Eye
and Hand Are Dissociated in Depth and Direction.
AB - Reaching behavior represents one of the basic aspects of human cognitive
abilities important for the interaction with the environment. Reaching movements
towards visual objects are controlled by mechanisms based on coordinate systems
that transform the spatial information of target location into appropriate motor
response. Although recent works have extensively studied the encoding of target
position for reaching in three-dimensional space at behavioral level, the
combined analysis of reach errors and movement variability has so far been
investigated by few studies. Here we did so by testing 12 healthy participants in
an experiment where reaching targets were presented at different depths and
directions in foveal and peripheral viewing conditions. Each participant executed
a memory-guided task in which he/she had to reach the memorized position of the
target. A combination of vector and gradient analysis, novel for behavioral data,
was applied to analyze patterns of reach errors for different combinations of
eye/target positions. The results showed reach error patterns based on both eye-
and space-centered coordinate systems: in depth more biased towards a space
centered representation and in direction mixed between space- and eye-centered
representation. We calculated movement variability to describe different
trajectory strategies adopted by participants while reaching to the different
eye/target configurations tested. In direction, the distribution of variability
between configurations that shared the same eye/target relative configuration was
different, whereas in configurations that shared the same spatial position of
targets, it was similar. In depth, the variability showed more similar
distributions in both pairs of eye/target configurations tested. These results
suggest that reaching movements executed in geometries that require hand and eye
dissociations in direction and depth showed multiple coordinate systems and
different trajectory strategies according to eye/target configurations and the
two dimensions of space.
PMID- 28690505
TI - Evidence for Separate Contributions of High and Low Spatial Frequencies during
Visual Word Recognition.
AB - Previous studies have shown that different spatial frequency information
processing streams interact during the recognition of visual stimuli. However, it
is a matter of debate as to the contributions of high and low spatial frequency
(HSF and LSF) information for visual word recognition. This study examined the
role of different spatial frequencies in visual word recognition using event
related potential (ERP) masked priming. EEG was recorded from 32 scalp sites in
30 English-speaking adults in a go/no-go semantic categorization task. Stimuli
were white characters on a neutral gray background. Targets were uppercase five
letter words preceded by a forward-mask (#######) and a 50 ms lowercase prime.
Primes were either the same word (repeated) or a different word (un-repeated)
than the subsequent target and either contained only high, only low, or full
spatial frequency information. Additionally within each condition, half of the
prime-target pairs were high lexical frequency, and half were low. In the full
spatial frequency condition, typical ERP masked priming effects were found with
an attenuated N250 (sub-lexical) and N400 (lexical-semantic) for repeated
compared to un-repeated primes. For HSF primes there was a weaker N250 effect
which interacted with lexical frequency, a significant reversal of the effect
around 300 ms, and an N400-like effect for only high lexical frequency word
pairs. LSF primes did not produce any of the classic ERP repetition priming
effects, however they did elicit a distinct early effect around 200 ms in the
opposite direction of typical repetition effects. HSF information accounted for
many of the masked repetition priming ERP effects and therefore suggests that
HSFs are more crucial for word recognition. However, LSFs did produce their own
pattern of priming effects indicating that larger scale information may still
play a role in word recognition.
PMID- 28690506
TI - Effective Connectivity between Ventral Occipito-Temporal and Ventral Inferior
Frontal Cortex during Lexico-Semantic Processing. A Dynamic Causal Modeling
Study.
AB - It has been suggested that dorsal and ventral pathways support distinct aspects
of language processing. Yet, the full extent of their involvement and their inter
regional connectivity in visual word recognition is still unknown. Studies
suggest that they might reflect the dual-route model of reading, with the dorsal
pathway more involved in grapho-phonological conversion during phonological
tasks, and the ventral pathway performing lexico-semantic access during semantic
tasks. Furthermore, this subdivision is also suggested at the level of the
inferior frontal cortex, involving ventral and dorsal parts for lexico-semantic
and phonological processing, respectively. In the present study, we assessed
inter-regional brain connectivity and task-induced modulations of brain activity
during a phoneme detection and semantic categorization tasks, using fMRI in
healthy subject. We used a dynamic causal modeling approach to assess inter
regional connectivity and task demand modulation within the dorsal and ventral
pathways, including the following network components: the ventral occipito
temporal cortex (vOTC; dorsal and ventral), the superior temporal gyrus (STG;
dorsal), the dorsal inferior frontal gyrus (dIFG; dorsal), and the ventral IFG
(vIFG; ventral). We report three distinct inter-regional interactions supporting
orthographic information transfer from vOTC to other language regions (vOTC ->
STG, vOTC -> vIFG and vOTC -> dIFG) regardless of task demands. Moreover, we
found that (a) during semantic processing (direct ventral pathway) the vOTC ->
vIFG connection strength specifically increased and (b) a lack of modulation of
the vOTC -> dIFG connection strength by the task that could suggest a more
general involvement of the dorsal pathway during visual word recognition. Results
are discussed in terms of anatomo-functional connectivity of visual word
recognition network.
PMID- 28690508
TI - Cortical Dynamics in Presence of Assemblies of Densely Connected Weight-Hub
Neurons.
AB - Experimental measurements of pairwise connection probability of pyramidal neurons
together with the distribution of synaptic weights have been used to construct
randomly connected model networks. However, several experimental studies suggest
that both wiring and synaptic weight structure between neurons show statistics
that differ from random networks. Here we study a network containing a subset of
neurons which we call weight-hub neurons, that are characterized by strong inward
synapses. We propose a connectivity structure for excitatory neurons that contain
assemblies of densely connected weight-hub neurons, while the pairwise connection
probability and synaptic weight distribution remain consistent with experimental
data. Simulations of such a network with generalized integrate-and-fire neurons
display regular and irregular slow oscillations akin to experimentally observed
up/down state transitions in the activity of cortical neurons with a broad
distribution of pairwise spike correlations. Moreover, stimulation of a model
network in the presence or absence of assembly structure exhibits responses
similar to light-evoked responses of cortical layers in optogenetically modified
animals. We conclude that a high connection probability into and within
assemblies of excitatory weight-hub neurons, as it likely is present in some but
not all cortical layers, changes the dynamics of a layer of cortical
microcircuitry significantly.
PMID- 28690507
TI - The Relationship between Intrinsic Couplings of the Visual Word Form Area with
Spoken Language Network and Reading Ability in Children and Adults.
AB - Reading plays a key role in education and communication in modern society.
Learning to read establishes the connections between the visual word form area
(VWFA) and language areas responsible for speech processing. Using resting-state
functional connectivity (RSFC) and Granger Causality Analysis (GCA) methods, the
current developmental study aimed to identify the difference in the relationship
between the connections of VWFA-language areas and reading performance in both
adults and children. The results showed that: (1) the spontaneous connectivity
between VWFA and the spoken language areas, i.e., the left inferior frontal
gyrus/supramarginal gyrus (LIFG/LSMG), was stronger in adults compared with
children; (2) the spontaneous functional patterns of connectivity between VWFA
and language network were negatively correlated with reading ability in adults
but not in children; (3) the causal influence from LIFG to VWFA was negatively
correlated with reading ability only in adults but not in children; (4) the RSFCs
between left posterior middle frontal gyrus (LpMFG) and VWFA/LIFG were positively
correlated with reading ability in both adults and children; and (5) the causal
influence from LIFG to LSMG was positively correlated with reading ability in
both groups. These findings provide insights into the relationship between VWFA
and the language network for reading, and the role of the unique features of
Chinese in the neural circuits of reading.
PMID- 28690510
TI - EEG Based Monitoring of General Anesthesia: Taking the Next Steps.
PMID- 28690511
TI - NeuroTessMesh: A Tool for the Generation and Visualization of Neuron Meshes and
Adaptive On-the-Fly Refinement.
AB - Gaining a better understanding of the human brain continues to be one of the
greatest challenges for science, largely because of the overwhelming complexity
of the brain and the difficulty of analyzing the features and behavior of dense
neural networks. Regarding analysis, 3D visualization has proven to be a useful
tool for the evaluation of complex systems. However, the large number of neurons
in non-trivial circuits, together with their intricate geometry, makes the
visualization of a neuronal scenario an extremely challenging computational
problem. Previous work in this area dealt with the generation of 3D polygonal
meshes that approximated the cells' overall anatomy but did not attempt to deal
with the extremely high storage and computational cost required to manage a
complex scene. This paper presents NeuroTessMesh, a tool specifically designed to
cope with many of the problems associated with the visualization of neural
circuits that are comprised of large numbers of cells. In addition, this method
facilitates the recovery and visualization of the 3D geometry of cells included
in databases, such as NeuroMorpho, and provides the tools needed to approximate
missing information such as the soma's morphology. This method takes as its only
input the available compact, yet incomplete, morphological tracings of the cells
as acquired by neuroscientists. It uses a multiresolution approach that combines
an initial, coarse mesh generation with subsequent on-the-fly adaptive mesh
refinement stages using tessellation shaders. For the coarse mesh generation, a
novel approach, based on the Finite Element Method, allows approximation of the
3D shape of the soma from its incomplete description. Subsequently, the adaptive
refinement process performed in the graphic card generates meshes that provide
good visual quality geometries at a reasonable computational cost, both in terms
of memory and rendering time. All the described techniques have been integrated
into NeuroTessMesh, available to the scientific community, to generate,
visualize, and save the adaptive resolution meshes.
PMID- 28690509
TI - Models of Acetylcholine and Dopamine Signals Differentially Improve Neural
Representations.
AB - Biological and artificial neural networks (ANNs) represent input signals as
patterns of neural activity. In biology, neuromodulators can trigger important
reorganizations of these neural representations. For instance, pairing a stimulus
with the release of either acetylcholine (ACh) or dopamine (DA) evokes long
lasting increases in the responses of neurons to the paired stimulus. The
functional roles of ACh and DA in rearranging representations remain largely
unknown. Here, we address this question using a Hebbian-learning neural network
model. Our aim is both to gain a functional understanding of ACh and DA
transmission in shaping biological representations and to explore neuromodulator
inspired learning rules for ANNs. We model the effects of ACh and DA on synaptic
plasticity and confirm that stimuli coinciding with greater neuromodulator
activation are over represented in the network. We then simulate the
physiological release schedules of ACh and DA. We measure the impact of
neuromodulator release on the network's representation and on its performance on
a classification task. We find that ACh and DA trigger distinct changes in neural
representations that both improve performance. The putative ACh signal
redistributes neural preferences so that more neurons encode stimulus classes
that are challenging for the network. The putative DA signal adapts synaptic
weights so that they better match the classes of the task at hand. Our model thus
offers a functional explanation for the effects of ACh and DA on cortical
representations. Additionally, our learning algorithm yields performances
comparable to those of state-of-the-art optimisation methods in multi-layer
perceptrons while requiring weaker supervision signals and interacting with
synaptically-local weight updates.
PMID- 28690512
TI - Bioinspired Architecture Selection for Multitask Learning.
AB - Faced with a new concept to learn, our brain does not work in isolation. It uses
all previously learned knowledge. In addition, the brain is able to isolate the
knowledge that does not benefit us, and to use what is actually useful. In
machine learning, we do not usually benefit from the knowledge of other learned
tasks. However, there is a methodology called Multitask Learning (MTL), which is
based on the idea that learning a task along with other related tasks produces a
transfer of information between them, what can be advantageous for learning the
first one. This paper presents a new method to completely design MTL
architectures, by including the selection of the most helpful subtasks for the
learning of the main task, and the optimal network connections. In this sense,
the proposed method realizes a complete design of the MTL schemes. The method is
simple and uses the advantages of the Extreme Learning Machine to automatically
design a MTL machine, eliminating those factors that hinder, or do not benefit,
the learning process of the main task. This architecture is unique and it is
obtained without testing/error methodologies that increase the computational
complexity. The results obtained over several real problems show the good
performances of the designed networks with this method.
PMID- 28690513
TI - Feature Selection Methods for Zero-Shot Learning of Neural Activity.
AB - Dimensionality poses a serious challenge when making predictions from human
neuroimaging data. Across imaging modalities, large pools of potential neural
features (e.g., responses from particular voxels, electrodes, and temporal
windows) have to be related to typically limited sets of stimuli and samples. In
recent years, zero-shot prediction models have been introduced for mapping
between neural signals and semantic attributes, which allows for classification
of stimulus classes not explicitly included in the training set. While choices
about feature selection can have a substantial impact when closed-set accuracy,
open-set robustness, and runtime are competing design objectives, no systematic
study of feature selection for these models has been reported. Instead, a
relatively straightforward feature stability approach has been adopted and
successfully applied across models and imaging modalities. To characterize the
tradeoffs in feature selection for zero-shot learning, we compared correlation
based stability to several other feature selection techniques on comparable data
sets from two distinct imaging modalities: functional Magnetic Resonance Imaging
and Electrocorticography. While most of the feature selection methods resulted in
similar zero-shot prediction accuracies and spatial/spectral patterns of selected
features, there was one exception; A novel feature/attribute correlation approach
was able to achieve those accuracies with far fewer features, suggesting the
potential for simpler prediction models that yield high zero-shot classification
accuracy.
PMID- 28690514
TI - Synergistic Effects on the Elderly People's Motor Control by Wearable Skin
Stretch Device Combined with Haptic Joystick.
AB - Cutaneous sensory feedback can be used to provide additional sensory cues to a
person performing a motor task where vision is a dominant feedback signal. A
haptic joystick has been widely used to guide a user by providing force feedback.
However, the benefit of providing force feedback is still debatable due to
performance dependency on factors such as the user's skill-level, task
difficulty. Meanwhile, recent studies have shown the feasibility of improving a
motor task performance by providing skin-stretch feedback. Therefore, a
combination of two aforementioned feedback types is deemed to be promising to
promote synergistic effects to consistently improve the person's motor
performance. In this study, we aimed at identifying the effect of the combined
haptic and skin-stretch feedbacks on the aged person's driving motor performance.
For the experiment, 15 healthy elderly subjects (age 72.8 +/- 6.6 years) were
recruited and were instructed to drive a virtual power-wheelchair through four
different courses with obstacles. Four augmented sensory feedback conditions were
tested: no feedback, force feedback, skin-stretch feedback, and a combination of
both force and skin-stretch feedbacks. While the haptic force was provided to the
hand by the joystick, the skin-stretch was provided to the steering forearm by a
custom-designed wearable skin-stretch device. We tested two hypotheses: (i) an
elderly individual's motor control would benefit from receiving information about
a desired trajectory from multiple sensory feedback sources, and (ii) the benefit
does not depend on task difficulty. Various metrics related to skills and safety
were used to evaluate the control performance. Repeated measure ANOVA was
performed for those metrics with two factors: task scenario and the type of the
augmented sensory feedback. The results revealed that elderly subjects' control
performance significantly improved when the combined feedback of both haptic
force and skin-stretch feedback was applied. The proposed approach suggest the
feasibility to improve people's task performance by the synergistic effects of
multiple augmented sensory feedback modalities.
PMID- 28690515
TI - A Case of Facial Partial Unilateral Lentiginosis Treated with Low-Fluence 1,064
nm Q-Switched Neodymium-Doped Yttrium Aluminum Garnet Laser.
AB - Partial unilateral lentiginosis (PUL) is an unusual pigmentary disorder
characterized by numerous lentigines grouped within an area of normal skin.
Although treatment is not necessary, many patients with facial PUL seek medical
help for cosmetic reasons. There is no established standard treatment for PUL.
Conventional lasers may cause postinflammatory hyperpigmentation because
keratinocytes are injured during the process. Also, scarring, long downtime, and
pain are important issues. A 19-year-old patient with facial PUL was successfully
treated with low-fluence 1,064-nm Q-switched neodymium-doped yttrium aluminum
garnet (QS Nd:YAG) laser. Although the exact mechanism by which low-fluence 1,064
nm QS Nd:YAG laser improves pigmentary lesions is unclear, the terms "subcellular
selective photothermolysis" and "melanocyte apoptosis and replacement" have been
proposed. If appropriate measures are taken to monitor patient response during
and after the procedure, low-fluence 1,064-nm QS Nd:YAG laser may achieve good
cosmetic results in the treatment of PUL with a very safe and effective profile.
PMID- 28690516
TI - Eruptive Seborrheic Keratoses Restricted to Plaque/Patch-Stage Mycosis Fungoides.
AB - Eruptive seborrheic keratoses (ESK) are rare in dermatology. They are usually
inflammatory in nature and may be encountered as Leser-Trelat sign. ESK may also
be simultaneously observed with hepatic angiomas, chemotherapy, segmental
neurofibromatosis, HIV or erythrodermic pityriasis rubra pilaris, psoriasis, and
drug eruption. ESK may be transient and self-healing. Others recede after
successful treatment of the underlying disease. In some instances, seborrheic
keratoses may follow an isotopic response and remain strictly restricted to sites
of previous eczema, photo-exposition or tattoos. A patient with patch/plaque
lesions of classic-type mycosis fungoides (MF) presented sudden ESK that were
exclusively limited to the MF lesions. In conclusion, this patient combined an
isotopic response and ESK.
PMID- 28690517
TI - Erythema Gyratum Repens-Like Purpura in a Patient with Sjogren Syndrome.
AB - The etiology of purpura in Sjogren syndrome (SS) includes cryoglobulinemia,
hypergammaglobulinemia, and leukocytoclastic vasculitis (LCV). The clinical
symptoms of LCV associated with SS comprise palpable or nonpalpable purpura and
urticarial vasculitis. Here, we report a case of LCV presenting as erythema
gyratum repens (EGR)-like purpura in a 62-year-old woman with rheumatoid
arthritis and SS. EGR-like skin lesions, characterized by annular lesions with
expanding concentric pattern and coalescing to form a zebra-like pattern or grain
of wood pattern, can appear in various autoimmune conditions; however, EGR-like
eruption in SS is extremely rare. On the basis of the expansion pattern, we
considered that the EGR-like purpura in this case was elicited by urticarial
vasculitis accompanied by SS.
PMID- 28690518
TI - Trichoscopic Findings of Erosive Pustular Dermatosis of the Scalp Associated with
Gefitinib.
AB - Alopecia associated with epidermal growth factor receptor (EGFR) inhibitor
therapy is a rare cutaneous side effect with the potential to progress to
scarring alopecia. Thus, dermatologists should make an early diagnosis. We
present the case of a 57-year-old Japanese female with scarring alopecia
associated with gefitinib, which is an EGFR inhibitor, including trichoscopic
findings. The patient treated with gefitinib for non-small cell lung cancer
experienced skin rash and hair loss of the scalp. The scalp lesions appeared
similar to erosive pustular dermatosis of the scalp. Trichoscopic examination
showed follicular keratotic plugging, milky red areas, white patches, hair shaft
disorder, tapering hair, and absence of follicular opening. Histological
examination showed ruptured hair follicles with a perifollicular infiltration of
plasma cells, lymphocytes, and histiocytes. Oral minocycline and topical steroid
treatment produced no improvement. With a reduction in the gefitinib dosage,
alopecia gradually improved, although scarring remained. We consider these
trichoscopic findings and suspect that follicular keratotic plugging might be a
finding associated with scarring alopecia due to EGFR inhibitor therapy.
PMID- 28690519
TI - Delayed Diagnosis of Basal Cell Carcinoma of the Upper Lip: The Possible Role of
Incidental Multinucleated Foreign Body Giant Cells.
AB - Herpes simplex and basal cell carcinoma (BCC) can have similar clinical
presentations due to overlapping lesional morphology. We describe the unusual
case of a BCC masquerading as herpes labialis due to a possible false-positive
Tzanck smear. The confounding diagnosis led to a failed trial of valacyclovir and
subsequent loss of the patient for 1 year before the lesion was biopsied and
diagnosed as a BCC. This case report highlights the importance of careful
inspection of herpetic lesions and that further investigation should be pursued
if the etiology is uncertain or if the treatment is not yielding the expected
results.
PMID- 28690520
TI - Extraskeletal Chondroma of the Index Finger: A Case Report.
AB - Extraskeletal chondroma is defined as a rare, benign, cartilaginous tumor arising
from soft tissues such as tendons, tendon sheath synovia, and joint capsules with
no continuity to the periosteum or bone cortex. In histopathologic findings, the
tumor exhibits many lobular structures and some parts similar to hyaline
cartilage. Therefore, it is sometimes difficult to differentiate this tumor from
low-grade chondrosarcoma because of their similar histopathologic findings. In
order to prevent recurrence, it is necessary to remove the tumor as a whole,
including the capsule, so as not to leave any remnants of the tumor. In this
article, we report our treatment experience with a case of extraskeletal
chondroma in the index finger of a 63-year-old patient.
PMID- 28690521
TI - Breast Cancer Metastasis Masquerading as the Great Masquerader: Sebaceous Cell
Carcinoma.
AB - OBJECTIVE: We describe the case of a patient with metastatic breast cancer who
presented with eyelid margin thickening and madarosis more suggestive of
sebaceous cell carcinoma than metastatic disease. Histopathology confirmed
metastatic breast adenocarcinoma. CASE REPORT: A 59-year-old woman with a known
history of metastatic breast carcinoma actively enrolled in a clinical trial
presented with a thickened right upper eyelid margin with madarosis and without
ulceration. Although the possibility of metastasis was considered, a biopsy was
performed to ensure the patient did not have a primary eyelid malignancy such as
sebaceous cell carcinoma given her immunocompromised state. Histopathology
revealed metastatic breast adenocarcinoma. CONCLUSIONS: To the authors' best
knowledge, metastatic breast carcinoma presenting as eyelid margin thickening
without ulceration has not previously been reported. Eyelid metastasis is rare,
and this patient's clinical presentation was found to be unusual as well. It is
important to establish metastatic disease even in a small focus such as the
eyelid, as it may alter disease management.
PMID- 28690522
TI - Small Cell Cancer of the Genitourinary Tract: A Case Report and Review of the
Literature.
AB - Small cell carcinoma of the urinary tract is an extremely rare disease with very
few cases reported in the literature. Its clinical course is aggressive, and the
prognosis is poor. Here, we present a case of metastatic extrapulmonary small
cell carcinoma of the upper urinary tract in a 74-year-old African-American male.
He initially presented with gross hematuria, 20-pound weight loss, and abdominal
pain for 2 months. CT imaging showed a 14.0 * 7.0 * 16.0 cm retroperitoneal mass
within the left renal fossa; biopsy revealed a carcinoma which was positive for
synaptophysin and chromogranin. The patient also had detectable neuroendocrine
cells in his urine cytology, confirming the diagnosis of small cell carcinoma. He
was treated with carboplatin and etoposide as extrapolated from the treatment of
its pulmonary counterpart. Due to the rarity of urinary tract small cell
carcinoma, no randomized studies exist to guide therapy or management.
PMID- 28690523
TI - A Case Report Demonstrating the Potential Clinical Benefit of Exhaustive
Molecular Profiling in an Aggressive Muscle-Invasive High-Grade Metastatic
Urothelial Carcinoma.
AB - We present a muscle-invasive high-grade metastatic urothelial carcinoma patient,
aged 71 years, with rapid progression from the diagnosis and a poor prognosis
after 3 lines of treatment. A clinical exhaustive genomic profile was performed
with the goal of finding potential actionable molecular alterations. The patient
showed significant symptomatic and laboratory improvement with a nonstandard
chemotherapy combination treatment identified by the molecular profiling, which
would otherwise not have been considered. This approach illustrates the clinical
benefit of a comprehensive genomic analysis in an aggressive and refractory
urothelial carcinoma.
PMID- 28690524
TI - Erdheim-Chester Disease: Case Report with Aggressive Multisystem Manifestations
and Review of the Literature.
AB - Erdheim-Chester disease (ECD) is an extremely rare and aggressive form of non
Langerhans cell histiocytosis. ECD usually presents with bone pain in adults aged
40-60. Its etiology is unknown but it is thought to be either a reactive or
neoplastic disorder. Recently, mutation of the proto-oncogene BRAF (BRAFV600E)
has been found in more than 50% of cases. The multisystemic form of ECD is
associated with significant morbidity, which may arise due to histiocytic
infiltration of critical organ systems. The common sites of involvement are the
skeleton, central nervous system, cardiovascular system, lungs, retroperitoneum,
and skin. Current available treatment is interferon alpha as the first line of
treatment. Treatment with other agents is based on anecdotal case reports.
Cladribine, anakinra, and vemurafenib (BRAF inhibitor) are currently advocated as
promising second-line treatments for patients whose response to interferon alpha
is unsatisfactory. Herein, we are reporting a middle-aged Saudi male patient with
an aggressive type of ECD and highlighting the clinical, radiological, and
pathological manifestations associated with ECD and the various treatment options
and patient follow-up.
PMID- 28690525
TI - Primary Type3 (Non-ABC, Non-GCB) Subtype of Extranodal Diffuse Large B-Cell
Lymphoma of the Thyroid Bearing No MYD88 Mutation by Padlock Probe Hybridization.
AB - Primary extranodal malignant lymphoma of the thyroid is a rare entity composed of
mostly neoplastic transformation of germinal center-like B cells (GCB) or memory
B cells. Other B-cell-type malignancies arising primarily in the thyroid have
rarely been described. Immunohistochemical examination of autopsied primary
malignant lymphoma of the thyroid in an 83-year-old Japanese female revealed the
presence of a non-GCB subtype of diffuse large B-cell lymphoma (DLBCL) without
the typical codon 206 or 265 missense mutation of MYD88. The lack of the highly
oncogenic MYD88 gene mutation, frequently observed in DLBCL of the activated B
cell (ABC) subtype, and the detection of an extremely aggressive yet local
clinical phenotype demonstrated that the present case was an exceptional entity
of the type3 (non-GCB and non-ABC) subtype.
PMID- 28690526
TI - A Case of T Cell Lymphoma Treated by Korean Medicine Therapy Alone.
AB - This case report is aimed to investigate the effects of Korean medicine therapy
(KMT) alone including oral herbal medicine on treating a patient with atypical
peripheral CD4 T cell lymphoma. The oral medicine used is Hyunamdan made of heat
processed ginseng and Hangamdan S. An 87-year-old man who was diagnosed as having
atypical peripheral CD4 T cell lymphoma on November 30, 2015 was treated with KMT
from December 23, 2015 until October 22, 2016. The effectiveness of therapies was
evaluated with PET-CT scan as well as the change of the main sign of lymphoma.
The sizes of the right axillar and right external iliac lymph nodes decreased.
These results suggest that KMT can be an effective method to treat atypical
peripheral CD4 T cell lymphoma.
PMID- 28690527
TI - Interstitial Pneumonitis Secondary to Trastuzumab: A Case Report and Literature
Review.
AB - Interstitial lung disease is a rare complication of trastuzumab-based breast
cancer treatment with few case reports published. Herein, we report the case of a
67-year-old female with early-stage HER2-postitive breast cancer who developed
interstitial pneumonitis during cycle 5 of treatment with trastuzumab combined
with carboplatin and docetaxel. After supportive care and treatment with
prednisone, the patient showed rapid improvement of respiratory symptoms.
Retreatment with trastuzumab as a single agent led to worsening of symptoms and
required a second course of treatment with prednisone combined with
cyclophosphamide, which was followed by improvement of symptoms. In conclusion,
interstitial pneumonitis is a rare but life-threatening adverse event from
trastuzumab breast cancer treatment.
PMID- 28690528
TI - PEComa with Transcription Factor E3 Overexpression: A Diagnostic and Therapeutic
Challenge.
AB - PEComa with transcription factor E3 overexpression, most commonly through gene
rearrangement, represents a biologically distinct subset of disease. We present
here an illustrative case to highlight its diagnostic and therapeutic challenge
in the context of potential pathogenic signaling pathways.
PMID- 28690529
TI - Successful Treatment of Richter Transformation with Ibrutinib in a Patient with
Chronic Lymphocytic Leukemia following Allogeneic Hematopoietic Stem Cell
Transplant.
AB - Patients with chronic lymphocytic leukemia (CLL) who progress to Richter
transformation (RT) have a poor prognosis. Multi-agent chemotherapy regimens do
not have good response rates. There are few case reports on the use of ibrutinib
in RT. Here, we present a patient who was heavily pretreated for CLL, including
allogeneic stem cell transplant, and progressed to RT. She had a mixed response
to multi-agent chemotherapy and was started on ibrutinib. She had a complete
response for 16 months on single-agent ibrutinib with minimal toxicity.
PMID- 28690530
TI - Hodgkin Lymphoma Mimicking Osteomyelitis.
AB - Hodgkin lymphoma with symptomatic osseous involvement can have a similar
presentation to osteomyelitis. Common findings in symptoms, laboratory workup,
and imaging can make it very difficult to distinguish between the two diseases.
Excisional biopsy should be pursued if fine-needle biopsy is equivocal and
suspicion of lymphoma is high. We report a case of a 40-year-old man who
presented with a history of marine animal sting on his neck and later developed
erythema in the area, chest pain, constitutional symptoms, adenopathy, and
imaging classic for sternal osteomyelitis. Fortunately, initial biopsy prompted
the possibility of lymphoma, and further workup was initiated, which confirmed
Hodgkin lymphoma. This case is a good reminder that malignancies and infections
can share many common features, and keeping a broad differential diagnosis can be
lifesaving. Proper staging and risk stratification of Hodgkin lymphoma help
determine the optimal treatment.
PMID- 28690531
TI - Stem Cells in the Treatment of Refractory Chronic Migraines.
AB - BACKGROUND: Autologous adipose-derived stromal vascular fraction (SVF), which is
rich in mesenchymal stromal cells, has been reported to be effective for the
treatment of trigeminal neuropathic pain and chronic migraine and tension-type
headaches. It is possible that stem cell activity targets neurogenic
inflammation, which is a well-documented aspect of migraine pathogenesis.
METHODS: Adult patients with severe migraine-related disability as measured by
the Migraine Disability Assessment (MIDAS) score who failed botulinum toxin
injections and at least 3 prophylactic drugs were included in this study. The
primary outcome measure was the change in MIDAS score 3 months after treatment.
Standard liposuction was performed to obtain adipose tissue, from which SVF was
isolated by centrifugation. A sample of each patient's SVF was tested for the
number of nucleated cells and their viability. Between 8 and 10 mL of SVF with
2.5-8.6 million viable cells were injected into the pericranial, neck, and
trapezius muscles. RESULTS: One man and 8 women were enrolled in the study. The
mean age was 48 years, the mean duration of headaches was 16 years, the mean
number of prophylactic drugs tried was 10, and the mean MIDAS score at baseline
was 122. Three months after the procedure the mean MIDAS score was 88. Seven out
of 9 patients had a decrease in their MIDAS score, but only 2 had meaningful
improvement. CONCLUSION: The use of autologous adipose-derived SVF may be
effective in the treatment of chronic refractory migraines. It is possible that
the use of allogenic stem cells could offer a more practical and more effective
approach.
PMID- 28690532
TI - Safe Intravenous Thrombolysis after Traumatic Cardiopulmonary Resuscitation with
Rib Fractures: A Case Report.
AB - We report a case of successful intravenous thrombolysis for a distal middle
cerebral artery occlusion shortly after traumatic cardiopulmonary resuscitation
due to an episode of ventricular tachycardia. A high prevalence of fatal cardiac
arrhythmias in acute stroke patients raises the question of safety when
administrating thrombolytic therapy after traumatic cardiopulmonary
resuscitation; guidelines do not provide a satisfactory statement about this. Our
case suggests that intravenous tissue-type plasminogen activator for acute
ischemic stroke can be administered after a thorough risk-to-benefit evaluation
without major adverse effects in patients after traumatic cardiopulmonary
resuscitation, as bleeding complications seem rare and can be monitored and
treated.
PMID- 28690533
TI - Dysphagia in Perry Syndrome: Pharyngeal Pressure in Two Cases.
AB - BACKGROUND: To investigate the impact of dysphagia in Perry syndrome (PS), an
autosomal dominant parkinsonism caused by mutation of DCTN1, which is associated
with hypoventilation, depression, and weight loss. CASE PRESENTATION: We used
tongue pressure measurements and manofluorography to investigate swallowing
function in 2 patients with PS. Case 1, a 60-year-old male showing parkinsonism,
and case 2, a 49-year-old male admitted with pneumonia, were diagnosed as having
PS based on the DCTN1 gene analysis. Case 1 showed a pharyngeal retention of the
bolus on videofluorography (VF) and a few swallows were required for its passage
into the esophagus. However, tongue pressure and manometry were within the normal
range. This patient could eat a normal diet under supervision. Case 2 required
artificial ventilation and tube feeding on admission. The VF image showed a slow
transfer of the bolus, delayed swallow reflex, and pharyngeal retention of the
bolus that required several swallows for its passage into the esophagus. The
tongue pressure was within the normal range, but manometry showed a significant
decrease in pressure at the hypopharynx and upper esophageal sphincter. The oral
intake of the patients was limited to 2 cups of jelly per day. CONCLUSIONS: The
investigation of swallowing dysfunction of 2 cases of PS showed that maintaining
pharyngeal pressure within the normal range was very important for oral feeding
success and prognosis.
PMID- 28690534
TI - A Case of Rhegmatogenous Retinal Detachment at Late Stage following Endogenous
Bacterial Endophthalmitis.
AB - PURPOSE: To report a case of rhegmatogenous retinal detachment in the late stage,
despite the fact that it had previously been halted after intravitreal injection
of an antimicrobial agent against endogenous bacterial endophthalmitis (EBE).
CASE: This study involved a 62-year-old male who had previously been diagnosed
with septicemia due to liver abscess and the detection of Klebsiella pneumoniae
in a culture of his liver abscess, and who underwent ophthalmic examination after
his conjunctival hyperemia had failed to improve. Visual acuity could not be
measured due to his general condition being poor and his declining level of
consciousness. Slit lamp examination revealed bilateral iritis and cataracts, and
the fundus was invisible due to vitreous opacity. Ultrasonic B-mode examination
showed subretinal abscess and exudative retinal detachment, leading to the
diagnosis of EBE. Vitreous injections of antibiotics were administered to both of
his eyes. His right eye became affected by phthisis bulbi, but the condition in
his left eye subsided, leaving a scarred lesion near the macula. However,
complete retinal detachment occurred in his left eye approximately 10 months
after the vitreous injection. During vitreous surgery, proliferative membrane
formation was observed in the posterior pole area, and an irregular retinal break
was detected in the scar margin caused by the traction of the proliferative
membrane. After vitreous surgery, the retina was reattached under silicone oil.
CONCLUSION: In cases of EBE, even if the inflammation has previously subsided,
strict follow-up examinations are necessary, since complications such as
rhegmatogenous retinal detachment may occur at a late stage.
PMID- 28690535
TI - Femtosecond Laser in situ Keratomileusis Flap Creation in Narrow Palpebral
Fissure Eyes without Suction.
AB - PURPOSE: To evaluate a surgical technique used in eyes with narrow palpebral
fissure undergoing femtosecond laser flap creation without suction during laser
in situ keratomileusis (LASIK). METHODS: All data of 2 patient groups were
collected through chart review. Group 1 consisted of 6 eyes with narrow palpebral
fissure in which the suction ring was manually fixated and femtosecond laser was
applied accordingly. Thirty comparison cases were randomly drawn from among eyes
that underwent a standard LASIK procedure matched for age and preoperative
refraction (group 2). Only 1 eye of each patient was selected to compare the
refractive and visual outcomes between groups. RESULTS: In all group 1 eyes, the
flaps were created successfully with manual fixation of the suction ring without
suction. No eyes lost 2 or more lines of vision. No significant difference was
found in the safety and refractive outcomes between groups. CONCLUSION: Manual
fixation of the suction ring in eyes with narrow palpebral fissure without
suction was feasible for flap creation during LASIK.
PMID- 28690536
TI - Catastrophic Thermal Corneoscleral Injury Treated with Transplantation of Donor
Scleral Graft.
AB - BACKGROUND: The aim of this study is to report a patient with senile cataract
developing severe thermal corneoscleral injury during phacoemulsification, which
was treated with a donor scleral graft. CASE: Severe thermal corneoscleral injury
occurred during phacoemulsification in the right eye of a 74-year-old male. His
medical history was prostate hypertrophy. Visual acuity was hand motion and the
intraocular pressure was 3 mm Hg OD. There was heavy corneal stromal opacity with
intraocular fluid leakage. The patient underwent transplantation of a donor
scleral graft to the burn site. Histologically, the injured sclera showed
coagulation necrosis without inflammatory cell infiltration. An intraocular lens
was eventually fixed in the ciliary sulcus 7 months later. His visual acuity
remains at 2/20 OD. CONCLUSIONS: Transplantation of the donor scleral grafts is
useful to close the wound in catastrophic thermal injury.
PMID- 28690537
TI - Peripheral Retinal Neovascularization with Vitreous Hemorrhage in HIV
Retinopathy.
AB - We report a case of peripheral retinal neovascularization and vitreous hemorrhage
in the setting of HIV retinopathy that can serve to extend the clinical spectrum
of this condition. A 53-year-old African-American woman with AIDS was referred
for decreased vision in the left eye and was found to have peripheral retinal
neovascularization and vitreous hemorrhage. She had a workup that was negative
for etiologies of retinal ischemia. Peripheral laser photocoagulation was used to
treat areas of nonperfusion. To our knowledge, this is the first reported case of
peripheral retinal neovascularization and vitreous hemorrhage in the setting of
HIV retinopathy, and it can serve to extend the clinical spectrum of this
condition.
PMID- 28690538
TI - Cutaneous Neurofibroma of the Lacrimal Caruncule: A Case Report.
AB - We describe the case of a neurofibroma on the lacrimal caruncle of a female
patient with neurofibromatosis type 1 (NF1). NF1 is an autosomal dominant genetic
disease with a wide variety of clinical manifestations, one of the most common of
which is neurofibroma. The lesion was removed surgically under general anesthesia
and sent to histopathological analysis, which confirmed the clinical diagnosis of
a neurofibroma.
PMID- 28690539
TI - NeurimmiRs and Postoperative Delirium in Elderly Patients Undergoing Total
Hip/Knee Replacement: A Pilot Study.
AB - Objective: Postoperative delirium (POD) is a frequent complication after surgery
and its occurrence is associated with poor outcomes. The pathophysiology of this
complication is not clear, but identification of risk factors is important for
positive postoperative outcomes. The purpose of this study was to investigate the
associations between the preoperative expression levels of microRNA (miR)-146a,
miR-125b, and miR-181c in cerebrospinal fluid (CSF) and serum and the development
and severity of POD. Methods: Forty elderly patients aged 65 years old and older
admitted for elective total hip/knee replacement under spinal anesthesia.
Preoperatively, baseline cognitive function was assessed using the Mini-Mental
State Examination. Each patient was interviewed daily on the first and second
postoperative days. Delirium was diagnosed using the Confusion Assessment Method,
and delirium severity was measured using the Memorial Delirium Assessment Scale
(MDAS). Preoperative serum and CSF miR levels were determined by quantitative
real-time PCR (qRT-PCR). Results: POD was detected in 27.5% (11/40) of patients.
Up-regulation of miR-146a and miR-181c in CSF and down-regulation of miR-146a in
serum were observed preoperatively in patients who developed POD, while patients
with and without POD did not differ in serum or CSF levels of miR-125b. Delirious
patients had higher CSF/serum ratios of miR-146a and miR-181c levels than non
delirious patients. The lower CSF miR-146a and CSF/serum miR-146a ratios were
significantly associated with milder POD severity, represented by a lower MDAS
score. Conclusion: The dysregulation of preoperative miR-146a and miR-181c in CSF
and serum was associated with the development and severity of POD. These
NeurimmiRs might participate in the neuropathogenesis of POD, pending further
investigations. Clinical trial registration: this study was registered at
ClinicalTrials.gov (NCT02817386).
PMID- 28690541
TI - The Significance of the Sulfatase Pathway for Local Estrogen Formation in
Endometrial Cancer.
AB - Endometrial cancer (EC) is the most common estrogen-dependent gynecological
malignancy in the developed World. To investigate the local formation of
estradiol (E2), we first measured the concentrations of the steroid precursor
androstenedione (A-dione) and the most potent estrogen, E2, and we evaluated the
metabolism of A-dione, estrone-sulfate (E1-S), and estrone (E1) in cancerous and
adjacent control endometrium. Furthermore, we studied expression of the key genes
for estradiol formation via the aromatase and sulfatase pathways. A-dione and E2
were detected in cancerous and adjacent control endometrium. In cancerous
endometrium, A-dione was metabolized to testosterone, and no E2 was formed. Both,
E1-S and E1 were metabolized to E2, with increased levels of E2 seen in cancerous
tissue. There was no significant difference in expression of the key genes of the
aromatase (CYP19A1) and the sulfatase (STS, HSD17B1, HSD17B2) pathways in
cancerous endometrium compared to adjacent control tissue. The mRNA levels of
CYP19A1 and HSD17B1 were low, and HSD17B14, which promotes inactivation of E2,
was significantly down-regulated in cancerous endometrium, especially in patients
with lymphovascular invasion. At the protein level, there were no differences in
the levels of STS and HSD17B2 between cancerous and adjacent control tissue by
Western blotting, and immunohistochemistry revealed intense staining for STS and
HSD17B2, and weak staining for SULT1E1 and HSD17B1 in cancerous tissue. Our data
demonstrate that in cancerous endometrium, E2 is formed from E1-S via the
sulfatase pathway, and not from A-dione via the aromatase pathway.
PMID- 28690542
TI - Systematic Review and Meta-Analysis of the Efficacy and Safety of Combined
Epinephrine and Corticosteroid Therapy for Acute Bronchiolitis in Infants.
AB - Objective: To evaluate the effectiveness of combined epinephrine and
corticosteroid therapy for acute bronchiolitis in infants. Methods: Four
electronic databases (MEDLINE, EMBASE, CINAHL, and CENTRAL) were searched from
their inception to February 28, 2017 for studies involving infants aged less than
24 months with bronchiolitis which assessed the use of epinephrine and
corticosteroid combination therapy. The methodological quality of the included
studies was assessed using the Cochrane Collaboration's Risk of Bias Tool. A
random-effects meta-analysis was used to pool the effect estimates. The primary
outcomes were hospital admission rate and length of hospital stay. Results: Of
1,489 citations identified, 5 randomized controlled trials involving 1,157
patients were included. All studies were of high quality and low risk of bias.
Results of the meta-analysis showed no significant differences in the primary
outcomes. Hospitalization rate was reduced by combinatorial therapy of
epinephrine and corticosteroid in only one out of five studies, whereas pooled
data indicated no benefit over epinephrine plus placebo. Clinical severity scores
were significantly improved in all five RCTs when assessed individually, but no
benefit was observed compared to epinephrine monotherapy when the data were
pooled together. Pooled data showed that combination therapy was more effective
at improving oxygen saturation level (mean difference: -0.70; 95% confidence
interval: -1.17 to -0.22, p = 0.004). There was no difference in the risk of
serious adverse events in infants treated with the combined epinephrine and
corticosteroid therapy. Conclusions: Combination treatment of epinephrine and
dexamethasone was ineffective in reducing hospital admission and length of stay
among infants with bronchiolitis.
PMID- 28690540
TI - The Role of Microglia in Prion Diseases: A Paradigm of Functional Diversity.
AB - Inflammation is a major component of neurodegenerative diseases. Microglia are
the innate immune cells in the central nervous system (CNS). In the healthy
brain, microglia contribute to tissue homeostasis and regulation of synaptic
plasticity. Under disease conditions, they play a key role in the development and
maintenance of the neuroinflammatory response, by showing enhanced proliferation
and activation. Prion diseases are progressive chronic neurodegenerative
disorders associated with the accumulation of the scrapie prion protein PrPSc, a
misfolded conformer of the cellular prion protein PrPC. This review article
provides the current knowledge on the role of microglia in the pathogenesis of
prion disease. A large body of evidence shows that microglia can trigger
neurotoxic pathways contributing to progressive degeneration. Yet, microglia are
also crucial for controlling inflammatory, repair and regenerative processes.
This dual role of microglia is regulated by multiple pathways and evidences the
ability of these cells to polarize into distinct phenotypes with characteristic
functions. The awareness that the neuroinflammatory response is inextricably
involved in producing tissue damage as well as repair in neurodegenerative
disorders, opens new perspectives for the modulation of the immune system. A
better understanding of this complex process will be essential for developing
effective therapies for neurodegenerative diseases, in order to improve the
quality of life of patients and mitigating the personal, economic and social
consequences derived from these diseases.
PMID- 28690543
TI - Frontiers in Drug Research and Development for Inflammatory Bowel Disease.
AB - Inflammatory bowel disease (IBD) is idiopathic, lifelong, immune-mediated
diseases, for which curative therapies are not yet available. In the last 15
years, the introduction of monoclonal antibodies targeting tumor necrosis factor
alpha, a cytokine playing a key role in bowel inflammation, has revolutionized
treatment paradigms for IBD. Despite their proven long-term efficacy, however,
many patients do not respond or progressively lose response to these drugs. Major
advances of knowledge in immunology and pathophysiology of intestinal
inflammatory processes have made possible the identification of new molecular
targets for drugs, thus opening several new potential therapeutic opportunities
for IBD. The abnormal response of intestinal immunity to unknown antigens leads
to the activation of T helper lymphocytes and triggers the inflammatory cascade.
Sphingosine 1-phosphate receptor agonists negatively modulate the egress of
lymphocytes, inducted by antigen-presenting cells, from secondary lymphoid
tissues to intestinal wall. Leukocyte adhesion inhibitors (both anti-integrin and
anti-Mucosal Vascular Addressin Cell Adhesion Molecule 1) interfere with the
tissue homing processes. Activated T helper lymphocytes increase the levels of
pro-inflammatory cytokines, such as interleukin 12, 23, and 6, offering several
potential pharmacological interventions. The Janus kinases, intracellular enzymes
mediating the transduction of several cytokine signals, are other explored
targets for treating immune-mediated diseases. Finally, the impact of modulating
Smad7 pathway, which is responsible for the down-regulation of the
immunosuppressive cytokine transforming growth factor-beta signaling, is
currently under investigation. The purpose of this review is to discuss the most
promising molecules in late-stage clinical development, with a special emphasis
on pharmacological properties.
PMID- 28690544
TI - Lotus Leaf Aqueous Extract Reduces Visceral Fat Mass and Ameliorates Insulin
Resistance in HFD-Induced Obese Rats by Regulating PPARgamma2 Expression.
AB - Objectives: Lotus leaf is a kind of traditional Chinese medicine. We aimed to
explore the effects of lotus leaf aqueous extract (LLAE) on peroxisome
proliferative activated receptor gamma2 (PPARgamma2) expression in preadipocytes
and adipocytes and further investigate its effects on high fat diet (HFD)-induced
obese rats. Methods: pGL3-Enhancer-PPARgamma2 (625 bp)-Luc plasmid, a luciferase
reporter gene expression plasmid containing PPARgamma2 promoter, was stably
transfected into 3T3-L1 preadipocytes. PPARgamma2 promoter activities were
determined by assaying the luciferase activities. Then PPARgamma2 promoter
activities in preadipocytes and PPARgamma2 mRNA levels in human subcutaneous
adipocytes were measured after the administration with LLAE. Additionally, the
effects of LLAE on body weight, fat mass, glucose and lipid metabolism and the
expression of PPARgamma2, insulin receptor substrate 1 and glucose transporter 4
(GLUT4) in visceral adipose tissue (VAT) were measured in HFD-induced obese rats
treated with low or high dose [0.5 or 3.0 g crude drug/(kg.d)] LLAE for 6 weeks.
Results: Ten MUg/ml LLAE significantly increased the luciferase activities in 3T3
L1 cells and the stimulatory action reached 2.51 folds of controls when LLAE was
1000 MUg/ml (P < 0.01). After treating 3T3-L1 cells with 100 MUg/ml LLAE, the
stimulatory role peaked at 32 h where it was 2.58 folds of controls (P < 0.01).
Besides, 100 MUg/ml LLAE significantly increased PPARgamma2 mRNA levels in human
adipocytes to 1.91 folds of controls (P < 0.01). In HFD-induced obese rats,
administration with both low and high dose LLAE notably reduced visceral fat mass
by 45.5 and 58.4%, respectively, and significantly decreased fasting serum
insulin levels (P < 0.05). The high dose LLAE also significantly decreased
homeostasis model assessment of insulin resistance in obese rats (P < 0.05).
Furthermore, the mRNA levels of PPARgamma2 and GLUT4 in VAT of obese rats were
significantly increased when compared with control rats, and were notably
suppressed by LLAE intervention for 6 weeks (P < 0.05). Conclusion: LLAE
significantly reduces visceral fat mass and ameliorates insulin resistance in HFD
induced obese rats. These beneficial effects of LLAE may associate with its role
in stimulating PPARgamma2 expression in preadipocytes and subcutaneous adipocytes
and suppressing PPARgamma2 and GLUT4 expression in VAT.
PMID- 28690545
TI - Spatial Patterns of Excitation at Tissue and Whole Organ Level Due to Early
Afterdepolarizations.
AB - Early after depolarizations (EAD) occur in many pathological conditions, such as
congenital or acquired channelopathies, drug induced arrhythmias, and several
other situations that are associated with increased arrhythmogenicity. In this
paper we present an overview of the relevant computational studies on spatial EAD
dynamics in 1D, 2D, and in 3D anatomical models and discuss the relation of EADs
to cardiac arrhythmias. We also discuss unsolved problems and highlight new lines
of research in this area.
PMID- 28690546
TI - Repeated Excessive Exercise Attenuates the Anti-Inflammatory Effects of Exercise
in Older Men.
AB - Introduction/Purpose: A number of studies have investigated the effect of
training with a moderate exercise dose (3-6 h/weekly) on the inflammatory profile
in blood, and the data are inconsistent. Cross-sectional studies indicate a
positive effect of physical activity level on inflammation levels and risk of
metabolic disease. However, it is not clear whether this may be dose dependent
and if very prolonged repeated exercise therefore may be beneficial for low-grade
inflammation. Based on this we studied how excessive repeated prolonged exercise
influenced low-grade inflammation and adipose tissue anti-inflammatory macrophage
content in six older male recreationally trained cyclists. Low-grade inflammation
and adipose tissue macrophage content were investigated in six older trained men
(age: 61 +/- 4 years; VO2peak: 48 +/- 2 mL kg-1 min-1) following repeated
prolonged exercise. Methods: Cycling was performed daily for 14 days covering in
total 2,706 km (1,681 miles). Maximal oxygen uptake (VO2peak) was measured before
and after the cycling. Duration and intensity of the exercise were determined
from heart rates sampled during cycling. An adipose tissue biopsy from
subcutaneous abdominal fat and a blood sample were obtained at rest in the
overnight fasted state before and after the cycling. Anti-inflammatory adipose
tissue macrophages (ATM) were immunohistochemically stained in cross sectional
sections using a CD163 binding antibody. The ATM and adipocyte sizes were
analyzed blindly. Results: The cyclists exercised daily for 10 h and 31 +/- 37
min and average intensity was 53 +/- 1% of VO2peak. Body weight remained
unchanged and VO2peak decreased by 6 +/- 2% (P = 0.04). Plasma inflammatory
cytokines, TNFalpha and IL-18 remained unchanged, as did hsCRP, but plasma IL-6
increased significantly. CD163 macrophage content remained unchanged, as did
adipocyte cell size. The HbA1c was not significantly decreased, but there was a
trend (P < 0.07) toward an increased insulin resistance as estimated by the
Quicki Index. Conclusion: The regular prolonged exercise did not influence
abdominal adipose tissue inflammation, but the higher plasma IL-6 concentration
concurrent with a trend toward higher insulin resistance and decreased VO2peak
implies that the excessive amount of exercise probably attenuated the possible
potential anti-inflammatory effects of exercise.
PMID- 28690547
TI - Posture Allocation Revisited: Breaking the Sedentary Threshold of Energy
Expenditure for Obesity Management.
AB - There is increasing recognition that low-intensity physical activities of daily
life play an important role in achieving energy balance and that their societal
erosion through substitution with sedentary (mostly sitting) behaviors, whether
occupational or for leisure, impact importantly on the obesity epidemic. This has
generated considerable interest for better monitoring, characterizing, and
promoting countermeasures to sedentariness through a plethora of low-level
physical activities (e.g., active workstations, standing desks, sitting breaks),
amid the contention that altering posture allocation (lying, sitting, standing)
can modify energy expenditure to impact upon body weight regulation and health.
In addressing this contention, this paper first revisits the past and more recent
literature on postural energetics, with particular emphasis on potential
determinants of the large inter-individual variability in the energy cost of
standing and the impact of posture on fat oxidation. It subsequently analyses the
available data pertaining to various strategies by which posture allocations,
coupled with light physical activity, may increase energy expenditure beyond the
sedentary threshold, and their relevance as potential targets for obesity
management.
PMID- 28690548
TI - Optimization of Variable Ventilation for Physiology, Immune Response and
Surfactant Enhancement in Preterm Lambs.
AB - Preterm infants often require mechanical ventilation due to lung immaturity
including reduced or abnormal surfactant. Since cyclic stretch with cycle-by
cycle variability is known to augment surfactant release by epithelial cells, we
hypothesized that such in vivo mechanotransduction improves surfactant maturation
and hence lung physiology in preterm subjects. We thus tested whether breath-by
breath variability in tidal volume (VT) in variable ventilation (VV) can be tuned
for optimal performance in a preterm lamb model. Preterm lambs were ventilated
for 3 h with conventional ventilation (CV) or two variants of VV that used a
maximum VT of 1.5 (VV1) or 2.25 (VV2) times the mean VT. VT was adjusted during
ventilation to a permissive pCO2 target range. Respiratory mechanics were
monitored continuously using the forced oscillation technique, followed by
postmortem bronchoalveolar lavage and tissue collection. Both VVs outperformed CV
in blood gas parameters (pH, SaO2, cerebral O2 saturation). However, only VV2
lowered PaCO2 and had a higher specific respiratory compliance than CV. VV2 also
increased surfactant protein (SP)-B release compared to VV1 and stimulated its
production compared to CV. The production and release of proSP-C however, was
increased with CV compared to both VVs. There was more SP-A in both VVs than CV
in the lung, but VV2 downregulated SP-A in the lavage, whereas SP-D significantly
increased in CV in both the lavage and lung. Compared to CV, the cytokines IL
1beta, and TNFalpha decreased with both VVs with less inflammation during VV2.
Additionally, VV2 lungs showed the most homogeneous alveolar structure and least
inflammatory cell infiltration assessed by histology. CV lungs exhibited over
distension mixed with collapsed and interstitial edematous regions with
occasional hemorrhage. Following VV1, some lambs had normal alveolar structure
while others were similar to CV. The IgG serum proteins in the lavage, a marker
of leakage, were the highest in CV. An overall combined index of performance that
included physiological, biochemical and histological markers was the best in VV2
followed by VV1. Thus, VV2 outperformed VV1 by enhancing SP-B metabolism
resulting in open alveolar airspaces, less leakage and inflammation and hence
better respiratory mechanics.
PMID- 28690549
TI - Running Economy from a Muscle Energetics Perspective.
AB - The economy of running has traditionally been quantified from the mass-specific
oxygen uptake; however, because fuel substrate usage varies with exercise
intensity, it is more accurate to express running economy in units of metabolic
energy. Fundamentally, the understanding of the major factors that influence the
energy cost of running (Erun) can be obtained with this approach. Erun is
determined by the energy needed for skeletal muscle contraction. Here, we
approach the study of Erun from that perspective. The amount of energy needed for
skeletal muscle contraction is dependent on the force, duration, shortening,
shortening velocity, and length of the muscle. These factors therefore dictate
the energy cost of running. It is understood that some determinants of the energy
cost of running are not trainable: environmental factors, surface
characteristics, and certain anthropometric features. Other factors affecting
Erun are altered by training: other anthropometric features, muscle and tendon
properties, and running mechanics. Here, the key features that dictate the energy
cost during distance running are reviewed in the context of skeletal muscle
energetics.
PMID- 28690550
TI - Targeting Inflammation and Downstream Protein Metabolism in Sarcopenia: A Brief
Up-Dated Description of Concurrent Exercise and Leucine-Based Multimodal
Intervention.
AB - Sarcopenia is defined as the progressive loss of muscle mass with age, and poses
a serious threat to the physiological and psychological health of the elderly
population with consequential economic and social burdens. Chronic low-grade
inflammation plays a central role in the development of sarcopenia such that it
alters cellular protein metabolism to favor proteolysis over synthesis, and
thereby accelerates muscular atrophy. The purpose of this review is to highlight
how exercise and nutrition intervention strategies can attenuate or treat
sarcopenia. Resistance exercise increases not only muscle mass but also muscle
strength, while aerobic exercise is able to ameliorate the age-related metabolic
disorders. Concurrent exercise training integrates the advantages of both aerobic
and resistance exercise, and may exert a significant synergistic effect in the
aging organism. Higher protein intakes rich in the amino acid leucine appear to
restore skeletal muscle protein metabolism balance by rescuing protein synthesis
in older adults. There is good reason to believe that a multimodal treatment, a
combination of exercise and increased leucine consumption in the diet, can combat
some of the muscle loss associated with aging. Future research is needed to
consolidate these findings to humans, and to further clarify to what extent and
by which mechanisms protein metabolism might be directly involved in sarcopenia
pathogenesis and the multimodal treatment responses.
PMID- 28690551
TI - Impact of Chemical Analogs of 4-Hydroxybenzoic Acid on Coenzyme Q Biosynthesis:
From Inhibition to Bypass of Coenzyme Q Deficiency.
AB - Coenzyme Q is a lipid that participates to important physiological functions.
Coenzyme Q is synthesized in multiple steps from the precursor 4-hydroxybenzoic
acid. Mutations in enzymes that participate to coenzyme Q biosynthesis result in
primary coenzyme Q deficiency, a type of mitochondrial disease. Coenzyme Q10
supplementation of patients is the classical treatment but it shows limited
efficacy in some cases. The molecular understanding of the coenzyme Q
biosynthetic pathway allowed the design of experiments to bypass deficient
biosynthetic steps with analogs of 4-hydroxybenzoic acid. These molecules provide
the defective chemical group and can reactivate endogenous coenzyme Q
biosynthesis as demonstrated recently in yeast, mammalian cell cultures, and
mouse models of primary coenzyme Q deficiency. This mini review presents how the
chemical properties of various analogs of 4-hydroxybenzoic acid dictate the
effect of the molecules on CoQ biosynthesis and how the reactivation of
endogenous coenzyme Q biosynthesis may achieve better results than exogenous
CoQ10 supplementation.
PMID- 28690553
TI - A Historical Review of Diachrony and Semantic Dimensions of Trace in
Neurosciences and Lacanian Psychoanalysis.
AB - Experience leaves a trace in the nervous system through plasticity. However, the
exact meaning of the mnesic trace is poorly defined in current literature. This
article provides a historical review of the term trace in neuroscience and
psychoanalysis literature, to highlight two relevant aspects: the diachronic and
the semantic dimensions. There has been a general interest in diachrony, or a
form of evolution of the trace, but its indissociable semantic dimension remains
partially disregarded. Although frequently implied, the diachronic and semantic
dimensions of the trace are rarely clearly articulated. We situate this
discussion into the classical opposition of syntax, or rules of inscription of
the trace in the nervous system, and semantics, or the content of the trace,
which takes into consideration the attempt of the human being to build coherence.
A general observation is that the study of the term trace follows trends of the
thought of the given epoch. This historical analysis also reveals the decay of
the idea that the trace is reliable to the experience. From the articulation
between neurosciences and psychoanalysis in a historical perspective, this review
shows that the trend is to consider trace as a production of the subject,
resulting in a permanent rewriting in an attempt to give meaning to the
experience. This trend is becoming increasingly evident in light of recent
research in neurosciences and psychoanalysis.
PMID- 28690552
TI - The Role of Reactive Oxygen Species and Autophagy in Periodontitis and Their
Potential Linkage.
AB - Periodontitis is a chronic inflammatory disease that causes damage to periodontal
tissues, which include the gingiva, periodontal ligament, and alveolar bone. The
major cause of periodontal tissue destruction is an inappropriate host response
to microorganisms and their products. Specifically, a homeostatic imbalance
between reactive oxygen species (ROS) and antioxidant defense systems has been
implicated in the pathogenesis of periodontitis. Elevated levels of ROS acting as
intracellular signal transducers result in autophagy, which plays a dual role in
periodontitis by promoting cell death or blocking apoptosis in infected cells.
Autophagy can also regulate ROS generation and scavenging. Investigations are
ongoing to elucidate the crosstalk mechanisms between ROS and autophagy. Here, we
review the physiological and pathological roles of ROS and autophagy in
periodontal tissues. The redox-sensitive pathways related to autophagy, such as
mTORC1, Beclin 1, and the Atg12-Atg5 complex, are explored in depth to provide a
comprehensive overview of the crosstalk between ROS and autophagy. Based on the
current evidence, we suggest that a potential linkage between ROS and autophagy
is involved in the pathogenesis of periodontitis.
PMID- 28690554
TI - White Lies in Hand: Are Other-Oriented Lies Modified by Hand Gestures? Possibly
Not.
AB - Previous studies have shown that the hand-over-heart gesture is related to being
more honest as opposed to using self-centered dishonesty. We assumed that the
hand-over-heart gesture would also relate to other-oriented dishonesty, though
the latter differs highly from self-centered lying. In Study 1 (N = 79), we
showed that performing a hand-over-heart gesture diminished the tendency to use
other-oriented white lies and that the fingers crossed behind one's back gesture
was not related to higher dishonesty. We then pre-registered and conducted Study
2 (N = 88), which was designed following higher methodological standards than
Study 1. Contrary, to the findings of Study 1, we found that using the hand-over
heart gesture did not result in refraining from using other-oriented white lies.
We discuss the findings of this failed replication indicating the importance of
strict methodological guidelines in conducting research and also reflect on
relatively small effect sizes related to some findings in embodied cognition.
PMID- 28690555
TI - The Better-Than-Average Effect Is Observed Because "Average" Is Often Construed
as Below-Median Ability.
AB - Most people rate their abilities as better than "average" even though it is
statistically impossible for most people to have better-than-median abilities.
Some investigators explained this phenomenon in terms of a self-enhancement bias.
The present study complements this motivational explanation with the parsimonious
cognitive explanation that the phrase "average ability" may be interpreted as
below-median ability rather than median ability. We believe people tend to
construe an "average" target that is based on the most representative exemplar,
and this result in different levels of "average" in different domains.
Participants compared their abilities to those of an average person, typical
person, and a person whose abilities are at the 40th, 50th, or 60th percentile.
We found that participants' interpretation of "average" ability depended on the
perceived difficulty of the ability. For abilities perceived as easy (e.g.,
spoken and written expression), participants construed an "average" target at the
40th percentile (i.e., below-median ability) and showed a marked better-than
average effect. On the contrary, for abilities perceived to be difficult,
participants construed an "average" target at the median or even above the
median.
PMID- 28690556
TI - Sound Spectrum Influences Auditory Distance Perception of Sound Sources Located
in a Room Environment.
AB - Previous studies on the effect of spectral content on auditory distance
perception (ADP) focused on the physically measurable cues occurring either in
the near field (low-pass filtering due to head diffraction) or when the sound
travels distances >15 m (high-frequency energy losses due to air absorption).
Here, we study how the spectrum of a sound arriving from a source located in a
reverberant room at intermediate distances (1-6 m) influences the perception of
the distance to the source. First, we conducted an ADP experiment using pure
tones (the simplest possible spectrum) of frequencies 0.5, 1, 2, and 4 kHz. Then,
we performed a second ADP experiment with stimuli consisting of continuous
broadband and bandpass-filtered (with center frequencies of 0.5, 1.5, and 4 kHz
and bandwidths of 1/12, 1/3, and 1.5 octave) pink-noise clips. Our results showed
an effect of the stimulus frequency on the perceived distance both for pure tones
and filtered noise bands: ADP was less accurate for stimuli containing energy
only in the low-frequency range. Analysis of the frequency response of the room
showed that the low accuracy observed for low-frequency stimuli can be explained
by the presence of sparse modal resonances in the low-frequency region of the
spectrum, which induced a non-monotonic relationship between binaural intensity
and source distance. The results obtained in the second experiment suggest that
ADP can also be affected by stimulus bandwidth but in a less straightforward way
(i.e., depending on the center frequency, increasing stimulus bandwidth could
have different effects). Finally, the analysis of the acoustical cues suggests
that listeners judged source distance using mainly changes in the overall
intensity of the auditory stimulus with distance rather than the direct-to
reverberant energy ratio, even for low-frequency noise bands (which typically
induce high amount of reverberation). The results obtained in this study show
that, depending on the spectrum of the auditory stimulus, reverberation can
degrade ADP rather than improve it.
PMID- 28690557
TI - Security under Uncertainty: Adaptive Attackers Are More Challenging to Human
Defenders than Random Attackers.
AB - Game Theory is a common approach used to understand attacker and defender
motives, strategies, and allocation of limited security resources. For example,
many defense algorithms are based on game-theoretic solutions that conclude that
randomization of defense actions assures unpredictability, creating difficulties
for a human attacker. However, many game-theoretic solutions often rely on
idealized assumptions of decision making that underplay the role of human
cognition and information uncertainty. The consequence is that we know little
about how effective these algorithms are against human players. Using a
simplified security game, we study the type of attack strategy and the
uncertainty about an attacker's strategy in a laboratory experiment where
participants play the role of defenders against a simulated attacker. Our goal is
to compare a human defender's behavior in three levels of uncertainty
(Information Level: Certain, Risky, Uncertain) and three types of attacker's
strategy (Attacker's strategy: Minimax, Random, Adaptive) in a between-subjects
experimental design. Best defense performance is achieved when defenders play
against a minimax and a random attack strategy compared to an adaptive strategy.
Furthermore, when payoffs are certain, defenders are as efficient against random
attack strategy as they are against an adaptive strategy, but when payoffs are
uncertain, defenders have most difficulties defending against an adaptive
attacker compared to a random attacker. We conclude that given conditions of
uncertainty in many security problems, defense algorithms would be more efficient
if they are adaptive to the attacker actions, taking advantage of the attacker's
human inefficiencies.
PMID- 28690559
TI - Commentary: Reproducibility in Psychological Science: When Do Psychological
Phenomena Exist?
PMID- 28690558
TI - Blue-Enriched White Light Enhances Physiological Arousal But Not Behavioral
Performance during Simulated Driving at Early Night.
AB - Vigilance usually deteriorates over prolonged driving at non-optimal times of
day. Exposure to blue-enriched light has shown to enhance arousal, leading to
behavioral benefits in some cognitive tasks. However, the cognitive effects of
long-wavelength light have been less studied and its effects on driving
performance remained to be addressed. We tested the effects of a blue-enriched
white light (BWL) and a long-wavelength orange light (OL) vs. a control condition
of dim light on subjective, physiological and behavioral measures at 21:45 h.
Neurobehavioral tests included the Karolinska Sleepiness Scale and subjective
mood scale, recording of distal-proximal temperature gradient (DPG, as index of
physiological arousal), accuracy in simulated driving and reaction time in the
auditory psychomotor vigilance task. The results showed that BWL decreased the
DPG (reflecting enhanced arousal), while it did not improve reaction time or
driving performance. Instead, blue light produced larger driving errors than OL,
while performance in OL was stable along time on task. These data suggest that
physiological arousal induced by light does not necessarily imply cognitive
improvement. Indeed, excessive arousal might deteriorate accuracy in complex
tasks requiring precision, such as driving.
PMID- 28690560
TI - Teacher's Autonomy Support and Engagement in Math: Multiple Mediating Roles of
Self-efficacy, Intrinsic Value, and Boredom.
AB - Previous studies have highlighted the impacts of environmental factors (teacher's
autonomy support) and individual factors (self-efficacy, intrinsic value, and
boredom) on academic engagement. This study aimed to investigate these variables
and examine the relations among them. Three structural equation models tested the
multiple mediational roles of self-efficacy, intrinsic value, and boredom in the
relation between teacher's autonomy support and behavioral, emotional, and
cognitive engagement, respectively, in math. A total of 637 Chinese middle school
students (313 males, 324 females; mean age = 14.82) voluntarily participated in
this study. Results revealed that self-efficacy, intrinsic value, and boredom
played important and mediating roles between perceived teacher's autonomy support
and student engagement. Specifically, these three individual variables partly
mediated the relations between perceived teacher's autonomy support and
behavioral and cognitive engagement, while fully mediating the relation between
perceived teacher's autonomy support and emotional engagement. These findings
complement and extend the understanding of factors affecting students' engagement
in math.
PMID- 28690561
TI - Interparental Conflict Relative to Suicidal Ideation in Chinese Adolescents: The
Roles of Coping Strategies and Meaning in Life.
AB - The aim of this study was to explore the paths between interparental conflict and
Chinese adolescents' suicidal ideation. Altogether 931 adolescents (Mage = 17.84,
SD = 0.77, females = 531) completed the Dyadic Consensus Scale, Self-Report
Coping Scale, Meaning in Life Questionnaire, and Positive and Negative Suicide
Ideation questionnaires. Mediation analyses were conducted, focusing on the
relations between interparental conflict and suicidal ideation along with coping
styles and a sense of meaning in life. The results showed that interparental
conflict indirectly predicted adolescents' suicidal ideation via three mediators:
coping-approach strategies, presence of meaning, and the joint serial effects of
coping-approach strategies and presence of meaning in Chinese adolescents. In
addition, boys were more likely to be at risk for suicidal ideation than girls,
so were 10th graders compared to 11th graders. These findings supported a
combined distress-to-meaninglessness line of thinking along with the use of
coping-approach strategies to depress self-harm ideation. Generally,
interparental conflict should be kept out of youngsters' immediate vicinity as a
preventive measure of suicidal ideation.
PMID- 28690562
TI - Trait Cheerfulness Does Not Influence Switching Costs But Modulates Preparation
and Repetition Effects in a Task-Switching Paradigm.
AB - Many studies have shown the beneficial effect of positive emotions on various
cognitive processes, such as creativity and cognitive flexibility. Cheerfulness,
understood as an affective predisposition to sense of humor, has been associated
with positive emotions. So far, however, no studies have shown the relevance of
this dimension in cognitive flexibility processes. The aim of this research was
to analyze the relationship between cheerfulness and these processes. To this
end, we carried out two studies using a task-switching paradigm. Study 1 aimed at
analyzing whether high trait cheerfulness was related to better cognitive
flexibility (as measured by reduced task-switching costs), whereas Study 2 aimed
at replicating the pattern of data observed in Study 1. The total sample was
composed of 139 participants (of which 86 were women) selected according to their
high versus low scores in trait cheerfulness. In a random way, participants had
to judge whether the face presented to them in each trial was that of a man or a
woman (gender recognition task) or whether it expressed anger or happiness
(expressed emotion recognition task). We expected participants with high versus
low trait cheerfulness to show a lower task-switching cost (i.e., higher
cognitive flexibility). Results did not confirm this hypothesis. However, in both
studies, participants with high versus low trait cheerfulness showed a higher
facilitation effect when the stimuli attributes were repeated and also when a cue
was presented anticipating the demand to perform. We discuss the relevance of
these results for a better understanding of cheerfulness.
PMID- 28690563
TI - Modeling Infant i's Look on Trial t: Race-Face Preference Depends on i's Looking
Style.
AB - When employing between-infant designs young infants' looking style is related to
their development: Short looking (SL) infants are cognitively accelerated over
their long looking (LL) peers. In fact, looking style is a within-infant
variable, and depends on infant i's look distribution over trials. For the paired
array setting, a model is provided which specifies the probability, pi i ? [0,
1], that i is SL. The model is employed in a face preference study; 74 Caucasian
infants were longitudinally assessed at 3, 6, and 9 months. Each i viewed same
race (Caucasian) vs. other race (African) faces. Infants become SL with
development, but there are huge individual differences in rate of change over
age. Three month LL infants, [Formula: see text], preferred other race faces. SL
infants, [Formula: see text], preferring same race faces at 3, and other race
faces at 6 and 9 months. Looking style changes precede and may control changes in
face preference. Ignoring looking style can be misleading: Without considering
looking style, 3 month infants show no face preference.
PMID- 28690564
TI - Effects of Mobile Text Advertising on Consumer Purchase Intention: A Moderated
Mediation Analysis.
AB - Mobile shopping is increasing in prevalence and has become a necessary part of
many people's daily lives. However, one main channel for mobile shopping, mobile
shopping applications (apps), has not been thoroughly investigated. This study
focused on mobile text advertising delivered from mobile shopping apps using the
intention to purchase as the dependent variable for testing its marketing effect.
In the context of a promotion focus vs. a prevention focus, we used Higgins'
regulatory focus theory combined with Ajzen's TPB and Herzog's U&G to analyze the
mechanism by which consumers formulate an intention to purchase in a mobile
advertising context. This empirical study surveyed 320 consumers who had made a
purchase using a mobile shopping app in the previous month. The results showed
that infotainment, irritation, and subjective norms were significantly associated
with attitudes; in turn, attitudes mediated the impact of these three factors on
the intention to purchase. Moreover, a high promotion focus not only strengthened
the positive effect of infotainment on attitudes but also intensified the
mediation effect of attitudes between infotainment and the intention to purchase.
A high prevention focus also consolidated the negative effect of irritation on
attitudes as well as reinforced the mediation effect of attitudes between
irritation and the intention to purchase. Furthermore, attitudes, subjective
norms, and perceived behavioral control collectively impacted the intention to
purchase. These findings shed light on ways to customize goods information in
mobile advertising and have strong theoretical and practical implications.
PMID- 28690565
TI - Evidence for Anger Saliency during the Recognition of Chimeric Facial Expressions
of Emotions in Underage Ebola Survivors.
AB - One of the crucial features defining basic emotions and their prototypical facial
expressions is their value for survival. Childhood traumatic experiences affect
the effective recognition of facial expressions of negative emotions, normally
allowing the recruitment of adequate behavioral responses to environmental
threats. Specifically, anger becomes an extraordinarily salient stimulus
unbalancing victims' recognition of negative emotions. Despite the plethora of
studies on this topic, to date, it is not clear whether this phenomenon reflects
an overall response tendency toward anger recognition or a selective proneness to
the salience of specific facial expressive cues of anger after trauma exposure.
To address this issue, a group of underage Sierra Leonean Ebola virus disease
survivors (mean age 15.40 years, SE 0.35; years of schooling 8.8 years, SE 0.46;
14 males) and a control group (mean age 14.55, SE 0.30; years of schooling 8.07
years, SE 0.30, 15 males) performed a forced-choice chimeric facial expressions
recognition task. The chimeric facial expressions were obtained pairing upper and
lower half faces of two different negative emotions (selected from anger, fear
and sadness for a total of six different combinations). Overall, results showed
that upper facial expressive cues were more salient than lower facial expressive
cues. This priority was lost among Ebola virus disease survivors for the chimeric
facial expressions of anger. In this case, differently from controls, Ebola virus
disease survivors recognized anger regardless of the upper or lower position of
the facial expressive cues of this emotion. The present results demonstrate that
victims' performance in the recognition of the facial expression of anger does
not reflect an overall response tendency toward anger recognition, but rather the
specific greater salience of facial expressive cues of anger. Furthermore, the
present results show that traumatic experiences deeply modify the perceptual
analysis of philogenetically old behavioral patterns like the facial expressions
of emotions.
PMID- 28690566
TI - Help Others and Yourself Eventually: Exploring the Relationship between Help
Giving and Employee Creativity under the Model of Perspective Taking.
AB - Although a plethora of studies have examined the antecedents of creativity,
empirical studies exploring the role of individual behaviors in relation to
creativity are relatively scarce. Drawing on the model of perspective taking,
this study examines the relationship between help-giving during creative problem
solving process and employee creativity. Specifically, we test perspective taking
as an explanatory mechanism and propose organization-based self-esteem as the
moderator. In a sample collected from a field survey of 247 supervisor
subordinate dyads from 2 large organizations in China at 3 time points, we find
that help-giving during creative problem solving process positively related with
perspective taking; perspective taking positively related with employees'
creativity; employees' organization-based self-esteem strengthened the link
between perspective taking and creativity; besides, there existed a moderated
mediation effect. We conclude this paper with discussions on the implications for
theory, research, and practice.
PMID- 28690567
TI - The Construct Validity of the German Academic Self-regulation Questionnaire (SRQ
A) within Primary and Secondary School Children.
AB - The assessment of students' motivation can be a powerful tool in enhancing and
understanding students' learning. One valid and often applied self-report measure
is the Academic Self-Regulation Questionnaire (SRQ-A) which is grounded in the
self-determination theory. However, to date, there is still no German equivalent
to the English version of this questionnaire. Therefore, the aim of the present
study was to adapt and validate the SRQ-A on a representative German student
sample, consisting of 672 children (327 girls), ages 8-14 from one primary and
two secondary German schools. First, the translation-back-translation method was
used to ensure the linguistic equivalence of the German questionnaire. Second,
item analysis of the generated scores of the German SRQ-A were conducted. Third,
the multidimensional factorial structure of the original measure was tested with
confirmatory factor analysis (CFA) using maximum likelihood estimation. Last,
additional construct validity of the German SRQ-A was tested using correlational
analyses with convergent and divergent measures. After conducting CFA, four items
were excluded from the original questionnaire, due to loadings lower than 0.40,
resulting in 28 items. The German SRQ-A showed good internal consistency for all
subscales, with Chronbach's alpha ranging between 0.75 and 0.88. The simplex
structure of the original measurement could also be confirmed, however, the four
factorial model could not be replicated. The measurement showed good convergent
and discriminant validity with other related questionnaires. In summary, the
German SRQ-A is a reliable and valid self-report instrument for the assessment of
self-determined motivational styles within the school context.
PMID- 28690568
TI - Fat Content Modulates Rapid Detection of Food: A Visual Search Study Using Fast
Food and Japanese Diet.
AB - Rapid detection of food is crucial for the survival of organisms. However,
previous visual search studies have reported discrepant results regarding the
detection speeds for food vs. non-food items; some experiments showed faster
detection of food than non-food, whereas others reported null findings concerning
any speed advantage for the detection of food vs. non-food. Moreover, although
some previous studies showed that fat content can affect visual attention for
food, the effect of fat content on the detection of food remains unclear. To
investigate these issues, we measured reaction times (RTs) during a visual search
task in which participants with normal weight detected high-fat food (i.e., fast
food), low-fat food (i.e., Japanese diet), and non-food (i.e., kitchen utensils)
targets within crowds of non-food distractors (i.e., cars). Results showed that
RTs for food targets were shorter than those for non-food targets. Moreover, the
RTs for high-fat food were shorter than those for low-fat food. These results
suggest that food is more rapidly detected than non-food within the environment
and that a higher fat content in food facilitates rapid detection.
PMID- 28690569
TI - The Effect of Different Phases of Synchrony on Pain Threshold in a Drumming Task.
AB - Behavioral synchrony has been linked to endorphin activity (Cohen et al., 2010;
Sullivan and Rickers, 2013; Sullivan et al., 2014; Tarr et al., 2015, 2016;
Weinstein et al., 2016). This has been called the synchrony effect. Synchrony has
two dominant phases of movement; in-phase and anti-phase. The majority of
research investigating synchrony's effect on endorphin activity has focused on in
phase synchrony following vigorous activities. The only research to investigate
the effects of anti-phase synchrony on endorphin activity found that anti-phase
synchronized rowing did not produce the synchrony effect (Sullivan et al., 2014).
Anti-phase synchrony, however, is counter-intuitive to the sport of rowing and
may have interfered with the synchrony effect. This study investigated the effect
of anti-phase synchrony on endorphin activity in a different task (i.e.,
drumming). University students (n = 30) were asked to drum solo and in in-phase
and anti-phase pairs for 3 min. Pain threshold was assessed as an indirect
indicator of endorphin activity prior to and following the task. Although the in
phase synchrony effect was not found, a repeated measures ANOVA found that there
was a significant difference in pain threshold change among the three conditions
[F(2,24) = 4.10, = 0.255, p < 0.05). Post hoc t-tests showed that the anti-phase
condition had a significantly greater pain threshold change than both the solo
and in-phase conditions at p < 0.05. This is the first time that anti-phase
synchrony has been shown to produce the synchrony effect. Because anti-phase
drumming may have required more attention between partners than in-phase
synchrony, it may have affected self-other merging (Tarr et al., 2014). These
results support Tarr et al.'s (2014) model that multiple mechanisms account for
the effect of synchrony on pain threshold, and suggest that different
characteristics of the activity may influence the synchrony effect.
PMID- 28690570
TI - Social Cognition in Children with High-Functioning Autism Spectrum Disorder and
Attention-Deficit/Hyperactivity Disorder. Associations with Executive Functions.
AB - Autism spectrum disorder (ASD) and attention deficit hyperactivity disorder
(ADHD) are neurodevelopmental disorders characterized by social impairments. The
first objective of this study was to analyze social cognition deficits of
children with ADHD, high-functioning ASD (HFASD), and typical development (TD) in
their performance on explicit and applied measures of theory of mind (ToM). The
second objective was to investigate the relationships between executive functions
and social cognition in HFASD and ADHD. One hundred and twenty-six 7- to 11-year
old children, 52 with HFASD, 35 with ADHD, and 39 with TD, performed the NEPSY-II
social perception subtests. Parents estimated their children's ToM skills using
the Theory of Mind Inventory (ToMI). Teacher-reported data from the Behavior
Rating Inventory of Executive Function (BRIEF) were also obtained. The HFASD and
ADHD groups showed worse performance on the verbal ToM task than the TD group,
and only the performance of the HFASD group was significantly lower than the TD
group on the contextual ToM task. Parents also estimated that the HFASD group had
more difficulties on the applied ToM than the ADHD and TD groups. Furthermore,
there is a different executive function-theory of mind link in the HFASD and ADHD
groups: behavioral regulation processes such as inhibition and emotional control
are more associated with social cognition in children with ADHD, whereas
metacognitive processes such as initiation and planning have a strong association
with social cognition in children with HFASD. These findings have implications
for understanding social perception deficits in neurodevelopmental disorders,
highlighting the need for early intervention.
PMID- 28690571
TI - The Correlation among Neural Dynamic Processing of Conflict Control, Testosterone
and Cortisol Levels in 10-Year-Old Children.
AB - Cognitive control is related to goal-directed self-regulation abilities, which is
fundamental for human development. Conflict control includes the neural processes
of conflict monitoring and conflict resolution. Testosterone and cortisol are
essential hormones for the development of cognitive functions. However, there are
no studies that have investigated the correlation of these two hormones with
conflict control in preadolescents. In this study, we aimed to explore whether
testosterone, cortisol, and testosterone/cortisol ratio worked differently for
preadolescent's conflict control processes in varied conflict control tasks.
Thirty-two 10-year-old children (16 boys and 16 girls) were enrolled. They were
instructed to accomplish three conflict control tasks with different conflict
dimensions, including the Flanker, Simon, and Stroop tasks, and
electrophysiological signals were recorded. Salivary samples were collected from
each child. The testosterone and cortisol levels were determined by enzyme-linked
immunosorbent assay. The electrophysiological results showed that the incongruent
trials induced greater N2/N450 and P3/SP responses than the congruent trials
during neural processes of conflict monitoring and conflict resolution in the
Flanker and Stroop tasks. The hormonal findings showed that (1) the
testosterone/cortisol ratio was correlated with conflict control accuracy and
conflict resolution in the Flanker task; (2) the testosterone level was
associated with conflict control performance and neural processing of conflict
resolution in the Stroop task; (3) the cortisol level was correlated with
conflict control performance and neural processing of conflict monitoring in the
Simon task. In conclusion, in 10-year-old children, the fewer processes a task
needs, the more likely there is an association between the T/C ratios and the
behavioral and brain response, and the dual-hormone effects on conflict
resolution may be testosterone-driven in the Stroop and Flanker tasks.
PMID- 28690572
TI - Utilitarian Moral Judgment Exclusively Coheres with Inference from Is to Ought.
AB - Faced with moral choice, people either judge according to pre-existing
obligations (deontological judgment), or by taking into account the consequences
of their actions (utilitarian judgment). We propose that the latter coheres with
a more general cognitive mechanism - deontic introduction, the tendency to infer
normative ('deontic') conclusions from descriptive premises (is-ought inference).
Participants were presented with vignettes that allowed either deontological or
utilitarian choice, and asked to draw a range of deontic conclusions, as well as
judge the overall moral rightness of each choice separately. We predicted and
found a selective defeasibility pattern, in which manipulations that suppressed
deontic introduction also suppressed utilitarian moral judgment, but had little
effect on deontological moral judgment. Thus, deontic introduction coheres with
utilitarian moral judgment almost exclusively. We suggest a family of norm
generating informal inferences, in which normative conclusions are drawn from
descriptive (although value-laden) premises. This family includes deontic
introduction and utilitarian moral judgment as well as other informal inferences.
We conclude with a call for greater integration of research in moral judgment and
research into deontic reasoning and informal inference.
PMID- 28690573
TI - Changes of Swimmers' Emotional States during the Preparation of National
Championship: Do Recovery-Stress States Matter?
AB - This study examined the trajectories of emotional states and their within-person
synergies with perceived stress and recovery during a 4-month training period
preceding the French swimming championships. A Multilevel Growth Curve Analysis
approach was used with 16 high level swimmers. Five waves of assessments of
emotional states, perceived stress and recovery were completed. Results indicated
that emotional states were characterized by distinct trajectories during the
training period preceding a major competition. Specifically, significant positive
linear effects of time (i.e., linear increase over time) and negative quadratic
effects of squared time (i.e., inverted U shape over time) on anxiety, dejection
and anger were observed, whereas the opposite pattern of results was found for
happiness and excitement. Moreover, level 2 perceived stress and recovery (i.e.,
inter-individual predictors) were significantly associated with athletes'
unpleasant and pleasant emotional states respectively. At level 1, perceived
recovery (i.e., intra-individual predictor) was positively associated with
happiness and excitement and negatively related to anxiety, dejection and anger.
Finally, within-person interactions of general stress and recovery with time and
squared time reached significance for excitement, whereas within-person
interactions of specific and total stress with time and squared time reached
significance for anxiety. Overall, this study provided insights into the central
role played by perceived stress and recovery on the emotional states experienced
by high level swimmers. Operational strategies were suggested in order to
optimize the stress-recovery balance and in turn the athletes' emotional states
during a complete training program.
PMID- 28690574
TI - An Experimental Study on the Attribution of Personality Traits to Bullies and
Targets in a Workplace Setting.
AB - Previous studies on the personality of bullies and targets have exclusively been
based on self-report. Against this backdrop we conducted a between group
experimental vignette study with three conditions, describing a bully, a target
and a control, respectively. Students (n = 242) were recruited as participants
and rated the target on the observer rating version of the NEO Five Factor
Inventory-Revised reflecting the personality dimensions Neuroticism,
Extroversion, Openness to experience, Agreeableness and Conscientiousness. A
MANOVA showed an overall significant effect of the experimental conditions. On
Neuroticism significant differences between all conditions were found with
targets rated highest and the control lowest. In terms of Extroversion the target
was rated as lower than the control and the bully. No main effect was found for
Openness. On Agreeableness the bully was rated as lower than both the target and
the control. The bully was rated lower on Conscientiousness than the control. The
significant differences reflected medium to large effect sizes. By and large the
results are in agreement with comparable self-report data. The results are
discussed in terms of practical implications and directions for future research
are outlined.
PMID- 28690575
TI - Reciprocal Relationship between Internet Addiction and Network-Related
Maladaptive Cognition among Chinese College Freshmen: A Longitudinal Cross-Lagged
Analysis.
AB - This study explored the reciprocal relationship between Internet addiction (IA)
and network-related maladaptive cognition (NMC) in Chinese college freshmen. A
short-term longitudinal survey with a sample of 213 college freshmen was
conducted in Shandong province, China. The results revealed that IA can
significantly predict the generation and development of NMCs, and that when such
maladaptive cognitions have been established, they can further adversely affect
the extent of the students' IA. A vicious cycle was observed between these two
variables, with IA having predictive priority in its relationship with NMC. This
study also determined that the relationship between these two variables was the
same for both males and females; therefore, the final model we established can be
extensively applied to Chinese college freshmen, regardless of gender.
Understanding the reciprocal relationship between these two variables can assist
in interventions in IA at the outset of students' college life.
PMID- 28690576
TI - Confronting Subtle Workplace Mistreatment: The Importance of Leaders as Allies.
PMID- 28690577
TI - Self-Objectification and Personal Values. An Exploratory Study.
AB - Self-objectification occurs when individuals treat themselves as objects to be
viewed and evaluated based upon appearance. Literature has largely elucidated
links between self-objectification and damaging outcomes in both men and women.
The purpose of the present study was to extend past research on the antecedents
of self-objectification. We were interested in the role played by specific
ideological components, i.e., higher order personal values (self-enhancement,
conservation, self-transcendence, and openness to change), in influencing the
degree to which individuals internalize the objectifying perspective of the
Western cultural milieu, i.e., self-objectify. Undergraduate participants (N =
371, 76.8% women) completed measures of self-objectification (i.e., body
surveillance and body shame), and endorsement of higher order values. Regression
analyses demonstrated that self-enhancement is linked to higher self
objectification in both men and women, whereas conservation is related only to
women's body surveillance. Self-transcendence seemed to act as a buffer against
men's body surveillance, whereas openness to change resulted as a buffer against
women's body surveillance. Implications are discusses.
PMID- 28690578
TI - Unconscious Processing of Facial Expressions in Individuals with Internet Gaming
Disorder.
AB - : Internet Gaming Disorder (IGD) is characterized by impairments in social
communication and the avoidance of social contact. Facial expression processing
is the basis of social communication. However, few studies have investigated how
individuals with IGD process facial expressions, and whether they have deficits
in emotional facial processing remains unclear. The aim of the present study was
to explore these two issues by investigating the time course of emotional facial
processing in individuals with IGD. A backward masking task was used to
investigate the differences between individuals with IGD and normal controls (NC)
in the processing of subliminally presented facial expressions (sad, happy, and
neutral) with event-related potentials (ERPs). The behavioral results showed that
individuals with IGD are slower than NC in response to both sad and neutral
expressions in the sad-neutral context. The ERP results showed that individuals
with IGD exhibit decreased amplitudes in ERP component N170 (an index of early
face processing) in response to neutral expressions compared to happy expressions
in the happy-neutral expressions context, which might be due to their
expectancies for positive emotional content. The NC, on the other hand, exhibited
comparable N170 amplitudes in response to both happy and neutral expressions in
the happy-neutral expressions context, as well as sad and neutral expressions in
the sad-neutral expressions context. Both individuals with IGD and NC showed
comparable ERP amplitudes during the processing of sad expressions and neutral
expressions. The present study revealed that individuals with IGD have different
unconscious neutral facial processing patterns compared with normal individuals
and suggested that individuals with IGD may expect more positive emotion in the
happy-neutral expressions context. HIGHLIGHTS: * The present study investigated
whether the unconscious processing of facial expressions is influenced by
excessive online gaming. A validated backward masking paradigm was used to
investigate whether individuals with Internet Gaming Disorder (IGD) and normal
controls (NC) exhibit different patterns in facial expression processing.* The
results demonstrated that individuals with IGD respond differently to facial
expressions compared with NC on a preattentive level. Behaviorally, individuals
with IGD are slower than NC in response to both sad and neutral expressions in
the sad-neutral context. The ERP results further showed (1) decreased amplitudes
in the N170 component (an index of early face processing) in individuals with IGD
when they process neutral expressions compared with happy expressions in the
happy-neutral expressions context, whereas the NC exhibited comparable N170
amplitudes in response to these two expressions; (2) both the IGD and NC group
demonstrated similar N170 amplitudes in response to sad and neutral faces in the
sad-neutral expressions context.* The decreased amplitudes of N170 to neutral
faces than happy faces in individuals with IGD might due to their less
expectancies for neutral content in the happy-neutral expressions context, while
individuals with IGD may have no different expectancies for neutral and sad faces
in the sad-neutral expressions context.
PMID- 28690579
TI - Editorial: Cognitive Hearing Mechanisms of Language Understanding: Short- and
Long-Term Perspectives.
PMID- 28690580
TI - Locke's View of the Hard Problem of Consciousness and Its Implications for
Neuroscience and Computer Science.
PMID- 28690581
TI - Corrigendum: PSYCHOACOUSTICS: a comprehensive MATLAB toolbox for auditory
testing.
AB - [This corrects the article on p. 712 in vol. 5, PMID: 25101013.].
PMID- 28690583
TI - Correlating Interictal Spikes with Sigma and Delta Dynamics during Non-Rapid-Eye
Movement-Sleep.
AB - Interictal spikes (IS) are one of the major hallmarks of epilepsy. Understanding
the factors promoting or suppressing IS would increase our comprehension of
epilepsy and possibly open new avenues for therapy. Sleep strongly influences
epileptic activity, and the modulatory effects of the different sleep stages on
IS have been studied for decades. However, several aspects are still disputed, in
particular the role of sleep spindles and slow waves in the activation of IS
during Non-REM sleep. Here, we correlate the rate of IS with quantitative
measures derived from stereo-EEG during one Non-REM cycle in 10 patients
suffering from drug-resistant epilepsy due to type 2 focal cortical dysplasia. We
show that the IS rate (ISR) is positively correlated with sigma power (a
surrogate for sleep-spindle density) but negatively correlated with delta power
(surrogate for slow wave activity). In addition, we present two new indices for
quantifying the spatial and temporal instability of sleep. We found that both
instability indices are correlated with a high ISR. The main contribution of this
study is to confirm the suppressive effect of stable deep sleep on IS. This
result might influence future guidelines for therapy of patients suffering from
epilepsy and sleep disorders.
PMID- 28690582
TI - Decreased Openness to Experience Is Associated with Migraine-Type Headaches in
Subjects with Lifetime Depression.
AB - INTRODUCTION: Migraine and depression frequently occur as comorbid conditions,
and it has been hypothesized that migraine with and without depression may have a
different genetic background. A distinct personality trait constellation has been
described in migraineurs. Less attention, however, was paid to personality
differences in migraineurs with and without depression which may also shed light
on differences in the neurobiological, background. The aim of our study was to
investigate big five personality traits, headaches, and lifetime depression (DEP)
in a large European general population sample. METHODS: Relationship between DEP,
Big Five Inventory personality traits, and headaches identified by the ID
Migraine Questionnaire were investigated in 3,026 individuals from Budapest and
Manchester with multivariate and logistic regression analyses. RESULTS: Both DEP
and migraine(ID) showed differences in personality traits. Neuroticism was an
independent risk factor for both conditions while a significant interaction
effect appeared between the two in the case of openness. Namely, subjects with
migraine(ID) and without DEP scored higher on openness compared to those who had
depression. CONCLUSION: While we confirmed previous results that high neuroticism
is a risk factor for both depression and migraine, openness to experience was
significantly lower in the co-occurrence of migraine and depression. Our results
suggest that increased openness, possibly manifested in optimal or advantageous
cognitive processing of pain experience in migraine may decrease the risk of co
occurrence of depression and migraine and thus may provide valuable insight for
newer prevention and intervention approaches in the treatment of these
conditions.
PMID- 28690584
TI - Decompression in Chiari Malformation: Clinical, Ocular Motor, Cerebellar, and
Vestibular Outcome.
AB - BACKGROUND: Treatment of Chiari malformation can include suboccipital
decompression with resection of one cerebellar tonsil. Its effects on ocular
motor and cerebellar function have not yet been systematically examined.
OBJECTIVE: To investigate whether decompression, including resection of one
cerebellar tonsil, leads to ocular motor, vestibular, or cerebellar deficits.
PATIENTS AND METHODS: Ten patients with Chiari malformation type 1 were
systematically examined before and after (1 week and 3 months) suboccipital
decompression with unilateral tonsillectomy. The work-up included a neurological
and neuro-ophthalmological examination, vestibular function, posturography, and
subjective scales. Cerebellar function was evaluated by ataxia rating scales.
RESULTS: Decompression led to a major subjective improvement 3 months after
surgery, especially regarding headache (5/5 patients), hyp-/dysesthesia (5/5
patients), ataxia of the upper limbs (4/5 patients), and paresis of the triceps
and interosseal muscles (2/2 patients). Ocular motor disturbances before
decompression were detected in 50% of the patients. These symptoms improved after
surgery, but five patients had new persisting mild ocular motor deficits 3 months
after decompression with unilateral tonsillectomy (i.e., smooth pursuit deficits,
horizontally gaze-evoked nystagmus, rebound, and downbeat nystagmus) without any
subjective complaints. Impaired vestibular (horizontal canal, saccular, and
utricular) function improved in five of seven patients with impaired function
before surgery. Posturographic measurements after surgery did not change
significantly. CONCLUSION: Decompression, including resection of one cerebellar
tonsil, leads to an effective relief of patients' preoperative complaints. It is
a safe procedure when performed with the help of intraoperative
electrophysiological monitoring, although mild ocular motor dysfunctions were
seen in half of the patients, which were fortunately asymptomatic.
PMID- 28690585
TI - Saccadic Impairments in Patients with the Norrbottnian Form of Gaucher's Disease
Type 3.
AB - BACKGROUND: Chronic neuronopathic Gaucher's disease type 3 (GD3) is relatively
frequent in northern Sweden. Besides multiple other neurological symptoms,
horizontal gaze palsy or oculomotor apraxia is common in GD3. OBJECTIVE: To
characterize the saccades in patients with Norrbottnian GD3 with respect to their
neurological and cognitive status using a computer-based eye-tracking technique.
METHODS: Horizontal and vertical reflexive saccades as well as antisaccades of
nine GD3 patients [4M/5F; 41.1 +/- 11.0 years; modified severity scoring tool
(mSST): 9.3 +/- 5.4; Montreal Cognitive Assessment (MoCA): 24.0 +/- 4.2] and age
matched controls were analyzed using EyeBrain T2, a head-mounted binocular eye
tracker. Systematic clinical assessment included the mSST, a valid tool for
monitoring the neurological progression in GD3 and MoCA. RESULTS: In Norrbottnian
GD3 patients, gain, peak, and average velocity (107.5 degrees /s +/- 41.8 vs.
283.9 degrees /s +/- 17.0; p = 0.0009) of horizontal saccades were reduced
compared to healthy controls (HCs). Regarding vertical saccades, only the average
velocity of downward saccades was decreased (128.6 degrees /s +/- 63.4 vs. 244.1
degrees /s +/- 50.8; p = 0.004). Vertical and horizontal saccadic latencies were
increased (294.3 ms +/- 37.0 vs. 236.5 ms +/- 22.4; p = 0.005) and the latency of
horizontal reflexive saccades was correlated with the mSST score (R2 = 0.80; p =
0.003). The latency of antisaccades showed association to MoCA score (R2 = 0.70;
p = 0.009). GD3 patients made more errors in the antisaccade task (41.5 +/- 27.6%
vs. 5.2 +/- 5.8%; p = 0.005), and the error rate tended to correlate with the
cognitive function measured in MoCA score (p = 0.06). CONCLUSION: The mean age of
41 years of our GD3 cohort reflects the increased life expectancy of patients in
the Norrbottnian area compared to other GD3 cohorts. Marked impairment of
horizontal saccades was evident in all patients, whereas vertical saccades showed
distinct impairment of downward velocity. Latency of reflexive saccades was
associated with the severity of neurological symptoms. Increased latency and
error rate in the antisaccade task were linked to cognitive impairment. The
assessment of saccades provides markers for neurological and neuropsychological
involvement in Norrbottnian GD3.
PMID- 28690586
TI - Modulations in the Peripheral Immune System of Glioblastoma Patient Is Connected
to Therapy and Tumor Progression-A Case Report from the IMMO-GLIO-01 Trial.
AB - Immune responses are important for efficient tumor elimination, also in immune
privileged organs such as the brain. Fostering antitumor immunity has therefore
become an important challenge in cancer therapy. This cannot only be achieved by
immunotherapies as already standard treatments such as radiotherapy and
chemotherapy modify the immune system. Consequently, the understanding of how the
tumor, the tumor microenvironment, and immune system are modulated by cancer
therapy is required for prognosis, prediction, and therapy adaption. The
prospective, explorative, and observational IMMO-GLIO-01 trial was initiated to
examine the detailed immune status and its modulation of about 50 patients
suffering from primary glioblastoma multiforme (GBM) or anaplastic astrocytoma
during standard therapy. Prior to the study, a flow cytometry-based assay was
established allowing the analysis of 34 immune cell subsets and their activation
state. Here, we present the case of the first and longest accompanied patient, a
53-year-old woman suffering from GBM in the front left lobe. In context of tumor
progression and therapy, we describe the modulation of the peripheral immune
status over 17 months. Distinct immune modulations that were connected to therapy
response or tumor progression were identified. Inter alia, a shift of CD4:CD8
ratio was observed that correlated with tumor progression. Twice we observed a
unique composition of peripheral immune cells that correlated with tumor
progression. Thus, following up these immune modulations in a closely-meshed
manner is of high prognostic and predictive relevance for supporting personalized
therapy and increasing therapy success. Clinical Trial registration:
ClinicalTrials.gov, identifier NCT02022384 (registered retrospectively on 13th of
December, 2013).
PMID- 28690587
TI - Brain Connectivity Patterns Dissociate Action of Specific Acupressure Treatments
in Fatigued Breast Cancer Survivors.
AB - Persistent fatigue is a pernicious symptom in many cancer survivors. Existing
treatments are limited or ineffective and often lack any underlying biologic
rationale. Acupressure is emerging as a promising new intervention for persistent
cancer-related fatigue; however, the underlying mechanisms of action are unknown.
Our previous investigations suggested that fatigued breast cancer survivors have
alterations in brain neurochemistry within the posterior insula and disturbed
functional connectivity to the default mode network (DMN), as compared to non
fatigued breast cancer survivors. Here, we investigated if insula and DMN
connectivity were modulated by self-administered acupressure by randomizing
breast cancer survivors (n = 19) to two distinct treatments: relaxing acupressure
or stimulating acupressure. All participants underwent proton magnetic resonance
spectroscopy of the posterior insula and functional connectivity magnetic
resonance imaging at baseline and immediately following 6 weeks of acupressure
self-treatment. As compared to baseline measures, relaxing acupressure decreased
posterior insula to dorsolateral prefrontal cortex connectivity, whereas
stimulating acupressure enhanced this connectivity (p < 0.05 corrected). For
relaxing but not stimulating acupressure, reduced connectivity was associated
with sleep improvement. In addition, connectivity of the DMN to the superior
colliculus was increased with relaxing acupressure and decreased with stimulating
acupressure, whereas DMN connectivity to the bilateral pulvinar was increased
with stimulating and decreased with relaxing acupressure (p < 0.05 corrected).
These data suggest that self-administered acupressure at different acupoints has
specificity in relation to their mechanisms of action in fatigued breast cancer
survivors.
PMID- 28690588
TI - Cannabis and Multiple Sclerosis-The Way Forward.
PMID- 28690589
TI - Corrigendum: New Treatments for Spinal Nerve Root Avulsion Injury.
AB - [This corrects the article on p. 135 in vol. 7, PMID: 27602018.].
PMID- 28690591
TI - Characterization of the Microbiome along the Gastrointestinal Tract of Growing
Turkeys.
AB - The turkey microbiome is largely understudied, despite its relationship with bird
health and growth, and the prevalence of human pathogens such as Campylobacter
spp. In this study we investigated the microbiome within the small intestine
(SI), caeca (C), large intestine (LI), and cloaca (CL) of turkeys at 6, 10, and
16 weeks of age. Eight turkeys were dissected within each age category and the
contents of the SI, C, LI, and CL were harvested. 16S rDNA based QPCR was
performed on all samples and samples for the four locations within three
birds/age group were sequenced using ion torrent-based sequencing of the 16S
rDNA. Sequencing data showed on a genus level, an abundance of Lactobacillus,
Streptococcus, and Clostridium XI (38.2, 28.1, and 13.0% respectively)
irrespective of location and age. The caeca exhibited the greatest microbiome
diversity throughout the development of the turkey. PICRUSt data predicted an
array of bacterial function, with most differences being apparent in the caeca of
the turkeys as they matured. QPCR revealed that the caeca within 10 week old
birds, contained the most Campylobacter spp. Understanding the microbial ecology
of the turkey gastrointestinal tract is essential in terms of understanding
production efficiency and in order to develop novel strategies for targeting
Campylobacter spp.
PMID- 28690592
TI - Assessment of MultiLocus Sequence Analysis As a Valuable Tool for the
Classification of the Genus Salinivibrio.
AB - The genus Salinivibrio includes obligatory halophilic bacteria and is commonly
isolated from hypersaline habitats and salted food products. They grow optimally
between 7.5 and 10% salts and are facultative anaerobes. Currently, this genus
comprises four species, one of them, S. costicola, with three subspecies. In this
study we isolated and characterized an additional 70 strains from solar salterns
located in different locations. Comparative 16S rRNA gene sequence analysis
identified these strains as belonging to the genus Salinivibrio but could not
differentiate strains into species-like groups. To achieve finer phylogenetic
resolution, we carried out a MultiLocus Sequence Analysis (MLSA) of the new
isolates and the type strains of the species of Salinivibrio based on the
individual as well as concatenated sequences of four housekeeping genes: gyrB,
recA, rpoA, and rpoD. The strains formed four clearly differentiated species-like
clusters called phylogroups. All of the known type and subspecies strains were
associated with one of these clusters except S. sharmensis. One phylogroup had no
previously described species coupled to it. Further DNA-DNA hybridization (DDH)
experiments with selected representative strains from these phylogroups permitted
us to validate the MLSA study, correlating the species level defined by the DDH
(70%) with a 97% cut-off for the concatenated MLSA gene sequences. Based on these
criteria, the novel strains forming phylogroup 1 could constitute a new species
while strains constructing the other three phylogroups are members of previously
recognized Salinivibrio species. S. costicola subsp. vallismortis co-occurs with
S. proteolyticus in phylogroup 4, and separately from other S. costicola strains,
indicating its need for reclassification. On the other hand, genome
fingerprinting analysis showed that the environmental strains do not form clonal
populations and did not cluster according to their site of cultivation. In future
studies regarding the classification and identification of new Salinivibrio
strains we recommend the following strategy: (i) initial partial sequencing of
the 16S rRNA gene for genus-level identification; (ii) sequencing and
concatenation of the four before mentioned housekeeping genes for species-level
discrimination; (iii) DDH experiments, only required when the concatenated MLSA
similarity values among a new isolate and other Salinivibrio strains are above
the 97% cut-off.
PMID- 28690590
TI - Secondary Bacterial Infections Associated with Influenza Pandemics.
AB - Lower and upper respiratory infections are the fourth highest cause of global
mortality (Lozano et al., 2012). Epidemic and pandemic outbreaks of respiratory
infection are a major medical concern, often causing considerable disease and a
high death toll, typically over a relatively short period of time. Influenza is a
major cause of epidemic and pandemic infection. Bacterial co/secondary infection
further increases morbidity and mortality of influenza infection, with
Streptococcus pneumoniae, Haemophilus influenzae, and Staphylococcus aureus
reported as the most common causes. With increased antibiotic resistance and
vaccine evasion it is important to monitor the epidemiology of pathogens in
circulation to inform clinical treatment and development, particularly in the
setting of an influenza epidemic/pandemic.
PMID- 28690593
TI - Fungal and Bacterial Pigments: Secondary Metabolites with Wide Applications.
AB - The demand for natural colors is increasing day by day due to harmful effects of
some synthetic dyes. Bacterial and fungal pigments provide a readily available
alternative source of naturally derived pigments. In contrast to other natural
pigments, they have enormous advantages including rapid growth, easy processing,
and independence of weather conditions. Apart from colorant, bacterial and fungal
pigments possess many biological properties such as antioxidant, antimicrobial
and anticancer activity. This review outlines different types of pigments. It
lists some bacterial and fungal pigments and current bacterial and fungal pigment
status and challenges. It also focuses on possible fungal and bacterial pigment
applications.
PMID- 28690594
TI - Toxin zeta Triggers a Survival Response to Cope with Stress and Persistence.
AB - Bacteria have evolved complex regulatory controls in response to various
environmental stresses. Protein toxins of the zeta superfamily, found in
prominent human pathogens, are broadly distributed in nature. We show that zeta
is a uridine diphosphate-N-acetylglucosamine (UNAG)-dependent ATPase whose
activity is inhibited in vitro by stoichiometric concentrations of epsilon2
antitoxin. In vivo, transient zeta expression promotes a reversible multi-level
response by altering the pool of signaling purine nucleotides, which leads to
growth arrest (dormancy), although a small cell subpopulation persists rather
than tolerating toxin action. High c-di-AMP levels (absence of phosphodiesterase
GdpP) decrease, and low c-di-AMP levels (absence of diadenylate cyclase DisA)
increase the rate of zeta persistence. The absence of CodY, a transition
regulator from exponential to stationary phase, sensitizes cells to toxin action,
and suppresses persisters formed in the DeltadisA context. These changes, which
do not affect the levels of stochastic ampicillin (Amp) persistence, sensitize
cells to toxin and Amp action. Our findings provide an explanation for the
connection between zeta-mediated growth arrest (with alterations in the GTP and c
di-AMP pools) and persistence formation.
PMID- 28690595
TI - Culture-Independent Analyses Reveal Novel Anaerolineaceae as Abundant Primary
Fermenters in Anaerobic Digesters Treating Waste Activated Sludge.
AB - Anaerobic digestion for biogas production is reliant on the tightly coupled
synergistic activities of complex microbial consortia. Members of the uncultured
A6 phylotype, within the phylum Chloroflexi, are among the most abundant genus
level-taxa of mesophilic anaerobic digester systems treating primary and surplus
sludge from wastewater treatment plants, yet are known only by their 16S rRNA
gene sequence. This study applied metagenomics to obtain a complete circular
genome (2.57 Mbp) from a representative of the A6 taxon. Preliminary annotation
of the genome indicates these organisms to be anaerobic chemoorganoheterotrophs
with a fermentative metabolism. Given their observed abundance, they are likely
important primary fermenters in digester systems. Application of fluorescence in
situ hybridisation probes designed in this study revealed their morphology to be
short filaments present within the flocs. The A6 were sometimes co-located with
the filamentous Archaea Methanosaeta spp. suggesting potential undetermined
synergistic relationships. Based on its genome sequence and morphology we propose
the species name Brevefilum fermentans gen. nov. sp. nov.
PMID- 28690596
TI - A Novel Approach to Predict the Growth of Staphylococcus aureus on Rice Cake.
AB - This study aimed to investigate the growth kinetics of Staphylococcus aureus on
rice cake and to determine the shelf life based on the probability model of the
increase in S. aureus contamination on rice cake. Secondary models were developed
based on the growth parameters derived from the Baranyi model at constant
temperatures (15, 25, 35, and 45 degrees C). External validation was then
conducted using additional data under experimental conditions not used in
development of the models to verify the performance and reliability of the
developed model through different goodness-of-fit indices. Furthermore, the
growth of S. aureus on rice cake under dynamic temperature was obtained with the
root mean square error (RMSE) of 0.218 and the 90.9% acceptable prediction rate.
In addition, probability models of the 1-, 2-, 3-, and 4-log increases of S.
aureus on rice cake were also developed from the data, which could provide the
probability and the time to a certain log increase. The results of validation
demonstrated that the developed predictive model and the obtained growth
parameters could be used for evaluating the growth behavior of S. aureus on rice
cake under different conditions, and qualified to supply sufficient information
for microbiological risk assessment studies of S. aureus on rice cake in Korea.
PMID- 28690597
TI - Close to the Edge: Growth Restrained by the NAD(P)H/ATP Formation Flux Ratio.
AB - Most fermentative microorganisms grow well-under anaerobic conditions managing a
balanced redox and appropriate energy metabolism, but a few species do exist in
which cells have to cope with inadequate energy recovery or capture and/or redox
balancing. Two cases of these species, i.e., the metabolically engineered
Saccharomyces cerevisiae enabling it to ferment xylose and Lactobacillus reuteri
fermenting glucose via the phosphoketolase pathway, are here used to introduce a
quantification parameter to capture what limits the growth rate of these
microorganisms under anaerobic conditions. This dimensionless parameter, the
cofactor formation flux ratio (RJ ), is the ratio between the redox formation
flux (JNADH+NADPH), and the energy carrier formation flux (JATP), which are
mainly connected to the central carbon pathways. Data from metabolic flux
analyses performed in previous and present studies were used to estimate the RJ
values. Even though both microorganisms possess different central pathways, a
similar relationship between RJ and the specific growth rate (MU) was found.
Furthermore, for both microorganisms external electron acceptors moderately
reduced the RJ -value, thereby raising the MU accordingly. Based on the emerging
profile of this relationship an interpretation is presented suggesting that this
quantitative analysis can be applied beyond the two microbial species
experimentally investigated in the current study to provide data for future
targeted strain development strategies.
PMID- 28690598
TI - Large Diversity and Original Structures of Acyl-Homoserine Lactones in Strain
MOLA 401, a Marine Rhodobacteraceae Bacterium.
AB - Quorum sensing (QS) is a density-dependent mechanism allowing bacteria to
synchronize their physiological activities, mediated by a wide range of signaling
molecules including N-acyl-homoserine lactones (AHLs). Production of AHL has been
identified in various marine strains of Proteobacteria. However, the chemical
diversity of these molecules still needs to be further explored. In this study,
we examined the diversity of AHLs produced by strain MOLA 401, a marine
Alphaproteobacterium that belongs to the ubiquitous Rhodobacteraceae family. We
combined an original biosensors-based guided screening of extract microfractions
with liquid chromatography coupled to mass spectrometry (MS), High Resolution
MS/MS and Nuclear Magnetic Resonance. This approach revealed the unsuspected
capacity of a single Rhodobacteraceae strain to synthesize 20 different
compounds, which are most likely AHLs. Also, some of these AHLs possessed
original features that have never been previously observed, including long (up to
19 carbons) and poly-hydroxylated acyl side chains, revealing new molecular
adaptations of QS to planktonic life and a larger molecular diversity than
expected of molecules involved in cell-cell signaling within a single strain.
PMID- 28690599
TI - Gut Dysbiosis and Adaptive Immune Response in Diet-induced Obesity vs. Systemic
Inflammation.
AB - A mutual interplay exists between adaptive immune system and gut microbiota.
Altered gut microbial ecosystems are associated with the metabolic syndrome,
occurring in most obese individuals. However, it is unknown why 10-25% of obese
individuals are metabolically healthy, while normal weight individuals can
develop inflammation and atherosclerosis. We modeled these specific metabolic
conditions in mice fed with a chow diet, an obesogenic but not inflammatory diet
mimicking healthy obesity, or Paigen diet-mimicking inflammation in the lean
subjects. We analyzed a range of markers and cytokines in the aorta, heart,
abdominal fat, liver and spleen, and metagenomics analyses were performed on
stool samples. T lymphocytes infiltration was found in the aorta and in the liver
upon both diets, however a significant increase in CD4+ and CD8+ cells was found
only in the heart of Paigen-fed animals, paralleled by increased expression of IL
1, IL-4, IL-6, IL-17, and IFN-gamma. Bacteroidia, Deltaproteobacteria, and
Verrucomicrobia dominated in mice fed Paigen diet, while Gammaproteobacteria,
Delataproteobacteria, and Erysipelotrichia were more abundant in obese mice. Mice
reproducing human metabolic exceptions displayed gut microbiota phylogenetically
distinct from normal diet-fed mice, and correlated with specific adaptive immune
responses. Diet composition thus has a pervasive role in co-regulating adaptive
immunity and the diversity of microbiota.
PMID- 28690600
TI - Differential Growth of Francisella tularensis, Which Alters Expression of
Virulence Factors, Dominant Antigens, and Surface-Carbohydrate Synthases, Governs
the Apparent Virulence of Ft SchuS4 to Immunized Animals.
AB - The gram-negative bacterium Francisella tularensis (Ft) is both a potential
biological weapon and a naturally occurring microbe that survives in arthropods,
fresh water amoeba, and mammals with distinct phenotypes in various environments.
Previously, we used a number of measurements to characterize Ft grown in Brain
Heart Infusion (BHI) broth as (1) more similar to infection-derived bacteria, and
(2) slightly more virulent in naive animals, compared to Ft grown in Mueller
Hinton Broth (MHB). In these studies we observed that the free amino acids in MHB
repress expression of select Ft virulence factors by an unknown mechanism. Here,
we tested the hypotheses that Ft grown in BHI (BHI-Ft) accurately displays a full
protein composition more similar to that reported for infection-derived Ft and
that this similarity would make BHI-Ft more susceptible to pre-existing, vaccine
induced immunity than MHB-Ft. We performed comprehensive proteomic analysis of Ft
grown in MHB, BHI, and BHI supplemented with casamino acids (BCA) and compared
our findings to published "omics" data derived from Ft grown in vivo. Based on
the abundance of ~1,000 proteins, the fingerprint of BHI-Ft is one of nutrient
deprived bacteria that-through induction of a stringent-starvation-like response
have induced the FevR regulon for expression of the bacterium's virulence
factors, immuno-dominant antigens, and surface-carbohydrate synthases. To test
the notion that increased abundance of dominant antigens expressed by BHI-Ft
would render these bacteria more susceptible to pre-existing, vaccine-induced
immunity, we employed a battery of LVS-vaccination and S4-challenge protocols
using MHB- and BHI-grown Ft S4. Contrary to our hypothesis, these experiments
reveal that LVS-immunization provides a barrier to infection that is
significantly more effective against an MHB-S4 challenge than a BHI-S4 challenge.
The differences in apparent virulence to immunized mice are profoundly greater
than those observed with primary infection of naive mice. Our findings suggest
that tularemia vaccination studies should be critically evaluated in regard to
the growth conditions of the challenge agent.
PMID- 28690602
TI - Geography, Ethnicity or Subsistence-Specific Variations in Human Microbiome
Composition and Diversity.
AB - One of the fundamental issues in the microbiome research is characterization of
the healthy human microbiota. Recent studies have elucidated substantial
divergences in the microbiome structure between healthy individuals from
different race and ethnicity. This review provides a comprehensive account of
such geography, ethnicity or life-style-specific variations in healthy microbiome
at five major body habitats-Gut, Oral-cavity, Respiratory Tract, Skin, and
Urogenital Tract (UGT). The review focuses on the general trend in the human
microbiome evolution-a gradual transition in the gross compositional structure
along with a continual decrease in diversity of the microbiome, especially of the
gut microbiome, as the human populations passed through three stages of
subsistence like foraging, rural farming and industrialized urban western life.
In general, gut microbiome of the hunter-gatherer populations is highly abundant
with Prevotella, Proteobacteria, Spirochaetes, Clostridiales, Ruminobacter etc.,
while those of the urban communities are often enriched in Bacteroides,
Bifidobacterium, and Firmicutes. The oral and skin microbiome are the next most
diverse among different populations, while respiratory tract and UGT microbiome
show lesser variations. Higher microbiome diversity is observed for oral-cavity
in hunter-gatherer group with higher prevalence of Haemophilus than agricultural
group. In case of skin microbiome, rural and urban Chinese populations show
variation in abundance of Trabulsiella and Propionibacterium. On the basis of
published data, we have characterized the core microbiota-the set of genera
commonly found in all populations, irrespective of their geographic locations,
ethnicity or mode of subsistence. We have also identified the major factors
responsible for geography-based alterations in microbiota; though it is not yet
clear which factor plays a dominant role in shaping the microbiome-nature or
nurture, host genetics or his environment. Some of the geographical/racial
variations in microbiome structure have been attributed to differences in host
genetics and innate/adaptive immunity, while in many other cases,
cultural/behavioral features like diet, hygiene, parasitic load, environmental
exposure etc. overshadow genetics. The ethnicity or population-specific
variations in human microbiome composition, as reviewed in this report, question
the universality of the microbiome-based therapeutic strategies and recommend for
geographically tailored community-scale approaches to microbiome engineering.
PMID- 28690603
TI - Oropharyngeal and Sputum Microbiomes Are Similar Following Exacerbation of
Chronic Obstructive Pulmonary Disease.
AB - Growing evidence suggests that the airway microbiota might be involved in acute
exacerbation of chronic obstructive pulmonary disease (AECOPD). Understanding
this relationship requires examination of a large-scale population for a long
duration to accurately monitor changes in the microbiome. This type of
longitudinal study requires an appropriate sampling strategy; two options are the
collection of sputum or oropharyngeal swabs. Comparative analysis of the changes
that occur in these two specimen types has not been previously performed. This
observational study was conducted to explore oropharyngeal microbial community
dynamics over time and to examine the relationship between oropharyngeal swabs
and sputum. A total of 114 samples were collected from four patients suffering
from severe AECOPD. Bacterial and fungal communities were evaluated using 16S
rRNA and ITS sequencing. Inter-individual differences were found in bacterial
community structure, but the core genera were shared by both sample types and
included 32 lineages. Most of the core genera were members of the phyla
Proteobacteria, Firmicutes and Ascomycota. Although the oropharyngeal samples
showed higher bacterial alpha diversity, the two sample types generated rather
similar taxonomic profiles. These results suggest that the sputum microbiome is
remarkably similar to the oropharyngeal microbiome. Thus, oropharyngeal swabs can
potentially be used instead of sputum samples for patients with exacerbation of
COPD.
PMID- 28690601
TI - Illuminating Messengers: An Update and Outlook on RNA Visualization in Bacteria.
AB - To be able to visualize the abundance and spatiotemporal features of RNAs in
bacterial cells would permit obtaining a pivotal understanding of many mechanisms
underlying bacterial cell biology. The first methods that allowed observing
single mRNA molecules in individual cells were introduced by Bertrand et al.
(1998) and Femino et al. (1998). Since then, a plethora of techniques to image
RNA molecules with the aid of fluorescence microscopy has emerged. Many of these
approaches are useful for the large eukaryotic cells but their adaptation to
study RNA, specifically mRNA molecules, in bacterial cells progressed relatively
slow. Here, an overview will be given of fluorescent techniques that can be used
to reveal specific RNA molecules inside fixed and living single bacterial cells.
It includes a critical evaluation of their caveats as well as potential
solutions.
PMID- 28690604
TI - Phenol Is the Initial Product Formed during Growth and Degradation of
Bromobenzene by Tropical Marine Yeast, Yarrowia lipolytica NCIM 3589 via an Early
Dehalogenation Step.
AB - Bromobenzene (BrB), a hydrophobic, recalcitrant organic compound, is listed by
the environmental protection agencies as an environmental and marine pollutant
having hepatotoxic, mutagenic, teratogenic, and carcinogenic effects. The
tropical marine yeast Yarrowia lipolytica 3589 was seen to grow aerobically on
BrB and displayed a maximum growth rate (MUmax) of 0.04 h-1. Furthermore, we also
observed an increase in cell size and sedimentation velocity for the cells grown
on BrB as compared to the glucose grown cells. The cells attached to the
hydrophobic bromobenzene droplets through its hydrophobic and acid-base
interactions. The BrB (0.5%, 47.6 mM) was utilized by the cells with the release
of a corresponding amount of bromide (12.87 mM) and yielded a cell mass of 1.86
g/L after showing 34% degradation in 96 h. Maximum dehalogenase activity of 16.16
U/mL was seen in the cell free supernatant after 24 h of growth. Identification
of metabolites formed as a result of BrB degradation, namely, phenol, catechol,
cis, cis muconic acid, and carbon dioxide were determined by LC-MS and GC-MS. The
initial attack on bromobenzene by Y. lipolytica cells lead to the transient
accumulation of phenol as an early intermediate which is being reported for the
first time. Degradation of phenol led to catechol which was degraded by the ortho
cleavage pathway forming cis, cis muconic acid and then to Krebs cycle
intermediates eventually leading to CO2 production. The study shows that
dehalogenation via an extracellular dehalogenase occurs prior to ring cleavage
with phenol as the preliminary degradative compound being produced. The yeast was
also able to grow on the degradative products, i.e., phenol and catechol, to
varying degrees which would be of potential relevance in the degradation and
remediation of xenobiotic environmental bromoaromatic pollutants such as
bromobenzene.
PMID- 28690423
TI - Search for new phenomena in events containing a same-flavour opposite-sign
dilepton pair, jets, and large missing transverse momentum in [Formula: see text]
[Formula: see text][Formula: see text] collisions with the ATLAS detector.
AB - Two searches for new phenomena in final states containing a same-flavour opposite
sign lepton (electron or muon) pair, jets, and large missing transverse momentum
are presented. These searches make use of proton-proton collision data, collected
during 2015 and 2016 at a centre-of-mass energy [Formula: see text] [Formula: see
text] by the ATLAS detector at the large hadron collider, which correspond to an
integrated luminosity of [Formula: see text]. Both searches target the pair
production of supersymmetric particles, squarks or gluinos, which decay to final
states containing a same-flavour opposite-sign lepton pair via one of two
mechanisms: a leptonically decaying Z boson in the final state, leading to a peak
in the dilepton invariant-mass distribution around the Z boson mass; and decays
of neutralinos (e.g. [Formula: see text]), yielding a kinematic endpoint in the
dilepton invariant-mass spectrum. The data are found to be consistent with the
Standard Model expectation. Results are interpreted in simplified models of
gluino-pair (squark-pair) production, and provide sensitivity to gluinos
(squarks) with masses as large as 1.70 [Formula: see text] (980 [Formula: see
text]).
PMID- 28690605
TI - Dicer-Like Genes Are Required for H2O2 and KCl Stress Responses, Pathogenicity
and Small RNA Generation in Valsa mali.
AB - Valsa mali (V. mali) is the causative agent of apple tree Valsa canker, which
heavily damages the production of apples in China. However, the biological roles
of the RNA interfering (RNAi) pathway in the pathogenicity of V. mali remain
unknown. Dicer-like proteins (DCLs) are important components that control the
initiation of the RNAi pathway. In this study, VmDCL1 and VmDCL2 were isolated
and functionally characterized in V. mali. VmDCL1 and VmDCL2 are orthologous in
evolution to the DCLs in Cryphonectria parasitica. The deletion of VmDCL1 and
VmDCL2 did not affect vegetative growth when the mutants (DeltaVmDCL1,
DeltaVmDCL2 and DeltaVmDCL1DCL2) and wild type strain 03-8 were grown on a PDA
medium at 25 degrees C in the dark. However, the colony of DeltaVmDCL1 increased
by 37.1% compared to the 03-8 colony in a medium containing 0.05% H2O2 3 days
after inoculation, and the growth of DeltaVmDCL1 was significantly inhibited in a
medium containing 0.5 M KCl at a ratio of 25.7%. Meanwhile, in the presence of
0.05% H2O2, the growth of DeltaVmDCL2 decreased by 34.5% compared with the growth
of 03-8, but DeltaVmDCL2 grew normally in the presence of 0.5 M KCl. More
importantly, the expression of VmDCL2 was up-regulated 125-fold during the
pathogen infection. In the infection assays using apple twigs, the pathogenicity
of DeltaVmDCL2 and DeltaVmDCL1DCL2 was significantly reduced compared with that
of 03-8 at a ratio of 24.7 and 41.3%, respectively. All defective phenotypes
could be nearly rescued by re-introducing the wild type VmDCL1 and VmDCL2
alleles. Furthermore, the number and length distribution of unique small RNAs
(unisRNAs) in the mutants and 03-8 were analyzed using deep sequencing. The
number of unisRNAs was obviously lower in DeltaVmDCL1, DeltaVmDCL2 and
DeltaVmDCL1DCL2 than that in 03-8, and the length distribution of the sRNAs also
markedly changed after the VmDCLs were deleted. These results indicated that
VmDCLs function in the H2O2 and KCl stress response, pathogenicity and generation
of sRNAs.
PMID- 28690607
TI - Modulation of Inter-kingdom Communication by PhcBSR Quorum Sensing System in
Ralstonia solanacearum Phylotype I Strain GMI1000.
AB - Ralstonia solanacearum is a ubiquitous soil-borne plant pathogenic bacterium,
which frequently encounters and interacts with other soil cohabitants in
competition for environmental niches. Ralsolamycin, which is encoded by the rmy
genes, has been characterized as a novel inter-kingdom interaction signal that
induces chlamydospore development in fungi. In this study, we provide the first
genetic evidence that the rmy gene expression is controlled by the PhcBSR quorum
sensing (QS) system in strain GMI1000. Mutation of phcB could lead to significant
reduction of the expression levels of the genes involved in ralsolamycin
biosynthesis. In addition, both the phcB and rmy mutants were attenuated in
induction of chlamydospore formation in Fusarium oxysporum f. cubense and
diminished in the ability to compete with the sugarcane pathogen Sporisorium
scitamineum. Agreeable with the pattern of QS regulation, transcriptional
expression analysis showed that the transcripts of the rmy genes were increased
along with the increment of the bacterial population density. Taken together, the
above findings provide new insights into the regulatory mechanisms that the QS
system involves in governing the ralsolamycin inter-kingdom signaling system.
PMID- 28690610
TI - Toll-Like Receptor 4 Inhibition Improves Oxidative Stress and Mitochondrial
Health in Isoproterenol-Induced Cardiac Hypertrophy in Rats.
AB - BACKGROUND: Inflammation remains a crucial factor for progression of cardiac
diseases and cardiac hypertrophy remains an important cause of cardiac failure
over all age groups. As a key regulator of inflammation, toll-like receptor 4
(TLR4) plays an important role in pathogenesis of cardiac diseases. Being an
important regulator of innate immunity, the precise pathway of TLR4-mediated
cardiac complications is yet to be established. Therefore, the primary objective
of the present study was to find the role of TLR4 in cardiac hypertrophy and the
molecular mechanism thereof. METHODS: Cardiac hypertrophy was induced with
administration of isoproterenol (5 mg/kg/day, sc). TLR4 receptor inhibitor RS-LPS
(lipopolysaccharide from the photosynthetic bacterium Rhodobacter sphaeroides; 5
MUg/day) and agonist lipopolysaccharide (LPS) (from Escherichia coli; 3.12
MUg/day) were administered through osmotic pump along with isoproterenol. Cardiac
hypertrophy as well as oxidative stress and mitochondrial parameters were
evaluated. RESULTS: Cardiac hypertrophy was confirmed with increased heart
weight/body weight ratio as well as assessment of hypertrophic markers in heart.
There was a marked increase in the TLR4 expression and oxidative stress along
with mitochondrial dysfunction in ISO group. TLR4 inhibition significantly
decreased heart weight/body weight ratio and ANP, collagen, and beta-MHC
expression and restored the disturbed cellular antioxidant flux. The
mitochondrial perturbations that were observed in hypertrophy heart was
normalized after administration of TLR4 inhibitor but not with the agonist. TLR4
agonism further exaggerated the oxidative stress in heart and hence accelerated
the disease development and progression. CONCLUSION: Our data show that increased
TLR4 ligand pool in cardiac hypertrophy may exaggerate the disease progression.
However, inhibition of TLR4 attenuated cardiac hypertrophy through reduced
cardiac redox imbalance and mitochondrial dysfunction.
PMID- 28690608
TI - Phylogenetic Tracings of Proteome Size Support the Gradual Accretion of Protein
Structural Domains and the Early Origin of Viruses from Primordial Cells.
AB - Untangling the origin and evolution of viruses remains a challenging proposition.
We recently studied the global distribution of protein domain structures in
thousands of completely sequenced viral and cellular proteomes with comparative
genomics, phylogenomics, and multidimensional scaling methods. A tree of life
describing the evolution of proteomes revealed viruses emerging from the base of
the tree as a fourth supergroup of life. A tree of domains indicated an early
origin of modern viral lineages from ancient cells that co-existed with the
cellular ancestors. However, it was recently argued that the rooting of our trees
and the basal placement of viruses was artifactually induced by small genome
(proteome) size. Here we show that these claims arise from misunderstanding and
misinterpretations of cladistic methodology. Trees are reconstructed unrooted,
and thus, their topologies cannot be distorted a posteriori by the rooting
methodology. Tracing proteome size in trees and multidimensional views of
evolutionary relationships as well as tests of leaf stability and
exclusion/inclusion of taxa demonstrated that the smallest proteomes were neither
attracted toward the root nor caused any topological distortions of the trees.
Simulations confirmed that taxa clustering patterns were independent of proteome
size and were determined by the presence of known evolutionary relatives in data
matrices, highlighting the need for broader taxon sampling in phylogeny
reconstruction. Instead, phylogenetic tracings of proteome size revealed a
slowdown in innovation of the structural domain vocabulary and four regimes of
allometric scaling that reflected a Heaps law. These regimes explained increasing
economies of scale in the evolutionary growth and accretion of kernel proteome
repertoires of viruses and cellular organisms that resemble growth of human
languages with limited vocabulary sizes. Results reconcile dynamic and static
views of domain frequency distributions that are consistent with the axiom of
spatiotemporal continuity that is tenet of evolutionary thinking.
PMID- 28690609
TI - Diversity, Prevalence, and Longitudinal Occurrence of Type II Toxin-Antitoxin
Systems of Pseudomonas aeruginosa Infecting Cystic Fibrosis Lungs.
AB - Type II toxin-antitoxin (TA) systems are most commonly composed of two genes
encoding a stable toxin, which harms the cell, and an unstable antitoxin that can
inactivate it. TA systems were initially characterized as selfish elements, but
have recently gained attention for regulating general stress responses
responsible for pathogen virulence, formation of drug-tolerant persister cells
and biofilms-all implicated in causing recalcitrant chronic infections. We use a
bioinformatics approach to explore the distribution and evolution of type II TA
loci of the opportunistic pathogen, Pseudomonas aeruginosa, across longitudinally
sampled isolates from cystic fibrosis lungs. We identify their location in the
genome, mutations, and gain/loss during infection to elucidate their function(s)
in stabilizing selfish elements and pathogenesis. We found (1) 26 distinct TA
systems, where all isolates harbor four in their core genome and a variable
number of the remaining 22 on genomic islands; (2) limited mutations in core
genome TA loci, suggesting they are not under negative selection; (3) no evidence
for horizontal transmission of elements with TA systems between clone types
within patients, despite their ability to mobilize; (4) no gain and limited loss
of TA-bearing genomic islands, and of those elements partially lost, the remnant
regions carry the TA systems supporting their role in genomic stabilization; (5)
no significant correlation between frequency of TA systems and strain ability to
establish as chronic infection, but those with a particular TA, are more
successful in establishing a chronic infection.
PMID- 28690611
TI - Insight into the Endocrine System and the Immune System: A Review of the
Inflammatory Role of Prolactin in Rheumatoid Arthritis and Psoriatic Arthritis.
AB - Rheumatoid arthritis (RA) is a chronic autoimmune disease that affects females
three times more frequently than males. A potential role for hormones, such as
prolactin (PRL), may in part explain this phenomenon. The risk of developing RA
is increased in women who are lactating after the first pregnancy, which might be
related to breastfeeding and the release of PRL. Other studies found a protective
effect of PRL on RA development. Some studies have reported that
hyperprolactinemia is more common in RA and serum PRL levels are correlated with
several disease parameters, although others could not confirm these findings.
Overall the plasma PRL levels are on average not elevated in RA. Previously, a
small number of open-label clinical trials using bromocriptine, which indirectly
decreases PRL levels, were performed in RA patients and showed clinical benefit,
although others found the opposite effect. Locally produced PRL at the site of
inflammation may have a crucial role in RA as well, as it has been shown that PRL
can be produced by synovial macrophages. Locally produced PRL has both pro
inflammatory and anti-inflammatory effects in arthritis. Psoriatic arthritis
(PsA) is also an autoinflammatory disease, in which the prolactin receptor is
also expressed in macrophages. The aim of this review is to provide an overview
of the potential role of PRL signaling in inflammatory joint diseases (RA and
PsA) and its potential as a therapeutic target.
PMID- 28690606
TI - A Highly Efficient CRISPR-Cas9-Mediated Large Genomic Deletion in Bacillus
subtilis.
AB - In Bacillus subtilis, large genomic deletions have been carried out for genome
reduction, antibiotic overproduction, and heterologous protein overexpression. In
view of the eco-friendliness of B. subtilis, it is critical that engineering
preserves its food-grade status and avoids leaving foreign DNA in the genome.
Existing methods of generating large genomic deletions leave antibiotic
resistance markers or display low mutation efficiency. In this study, we
introduced a clustered regularly interspaced short palindromic repeat-derived
genome engineering technique to develop a highly efficient method of generating
large genomic deletions in B. subtilis without any trace of foreign DNA. Using
our system, we produced 38 kb plipastatin-synthesizing pps operon deletion with
80% efficiency. The significant increase in mutation efficiency was due to
plasmids-delivered Streptococcus pyogenes-originated SpCas9, target-specific
sgRNA and a donor DNA template, which produces SpCas9/sgRNA endonuclease complex
continuously for attacking target chromosome until the mutagenic repair occurs.
Our system produced single-gene deletion in spo0A (~100%), point mutation (~68%)
and GFP gene insertion (~97%) in sigE and demonstrated its broad applicability
for various types of site-directed mutagenesis in B. subtilis.
PMID- 28690612
TI - Protection of Mice from Acute Graft-versus-Host Disease Requires CD28 Co
stimulation on Donor CD4+ Foxp3+ Regulatory T Cells.
AB - Acute graft-versus-host disease (aGvHD) is a major cause of morbidity and
mortality after allogeneic hematopoietic stem cell plus T cell transplantation
(allo-HSCT). In this study, we investigated the requirement for CD28 co
stimulation of donor CD4+ conventional (CD4+CD25-Foxp3-, Tconv) and regulatory
(CD4+CD25+Foxp3+, Treg) T cells in aGvHD using tamoxifen-inducible CD28 knockout
(iCD28KO) or wild-type (wt) littermates as donors of CD4+ Tconv and Treg. In the
highly inflammatory C57BL/6 into BALB/c allo-HSCT transplantation model, CD28
depletion on donor CD4+ Tconv reduced clinical signs of aGvHD, but did not
significantly prolong survival of the recipient mice. Selective depletion of CD28
on donor Treg did not abrogate protection of recipient mice from aGvHD until
about day 20 after allo-HSCT. Later, however, the pool of CD28-depleted Treg
drastically declined as compared to wt Treg. Consequently, only wt, but not CD28
deficient, Treg were able to continuously suppress aGvHD and induce long-term
survival of the recipient mice. To our knowledge, this is the first study that
specifically evaluates the impact of CD28 expression on donor Treg in aGvHD.
Moreover, the delayed kinetics of aGvHD lethality after transplantation of
iCD28KO Treg provides a novel animal model for similar disease courses found in
patients after allo-HSCT.
PMID- 28690613
TI - RelB+ Steady-State Migratory Dendritic Cells Control the Peripheral Pool of the
Natural Foxp3+ Regulatory T Cells.
AB - Thymus-derived natural Foxp3+ CD4+ regulatory T cells (nTregs) play a key role in
maintaining immune tolerance and preventing autoimmune disease. Several studies
indicate that dendritic cells (DCs) are critically involved in the maintenance
and proliferation of nTregs. However, the mechanisms how DCs manage to keep the
peripheral pool at constant levels remain poorly understood. Here, we describe
that the NF-kappaB/Rel family transcription factor RelB controls the frequencies
of steady-state migratory DCs (ssmDCs) in peripheral lymph nodes and their
numbers control peripheral nTreg homeostasis. DC-specific RelB depletion was
investigated in CD11c-Cre * RelBfl/fl mice (RelBDCko), which showed normal
frequencies of resident DCs in lymph nodes and spleen while the subsets of CD103-
Langerin- dermal DCs (dDCs) and Langerhans cells but not CD103+ Langerin+ dDC of
the ssmDCs in skin-draining lymph nodes were increased. Enhanced frequencies and
proliferation rates were also observed for nTregs and a small population of CD4+
CD44high CD25low memory-like T cells (Tml). Interestingly, only the Tml but not
DCs showed an increase in IL-2-producing capacity in lymph nodes of RelBDCko
mice. Blocking of IL-2 in vivo reduced the frequency of nTregs but increased the
Tml frequencies, followed by a recovery of nTregs. Taken together, by employing
RelBDCko mice with increased frequencies of ssmDCs our data indicate a critical
role for specific ssmDC subsets for the peripheral nTreg and IL-2+ Tml
frequencies during homeostasis.
PMID- 28690614
TI - What Else Can CD39 Tell Us?
AB - As the rate-limiting enzyme in ATP/ADP-AMP-adenosine pathway, CD39 would be a
novel checkpoint inhibitor target in preventing adenosine-triggered immune
suppressive effect. In addition, CD39hi Tregs, but not CD25hi Tregs, exhibit
sustained Foxp3 levels and functional abilities, indicating it could represent a
new specific marker of Tregs. Similarly, inhibition of CD39 enzymatic function at
the surface of tumor cells alleviates their immunosuppressive activity. Far from
conclusive, present research revealed that CD39 also dephosphorylated and thus
inactivated self- and pathogen-associated phosphoantigens of Vgamma9Vdelta2 T
cells, which may be the most promising subpopulation for cellular vaccine. CD39
is also tightly related to Th17 cells and can be regarded as a Th17 cells marker.
In this review, we focus on present research of CD39 ectoenzyme and provide
insights into its clinical application.
PMID- 28690615
TI - Impact of Early-Life Exposures to Infections, Antibiotics, and Vaccines on
Perinatal and Long-term Health and Disease.
AB - Essentially, all neonates are exposed to infections, antibiotics, or vaccines
early in their lives. This is especially true for those neonates born underweight
or premature. In contrast to septic adults and children who are at an increased
risk for subsequent infections, exposure to infection during the neonatal period
is not associated with an increased risk of subsequent infection and may be
paradoxically associated with reductions in late-onset sepsis (LOS) in the most
premature infants. Perinatal inflammation is also associated with a decreased
incidence of asthma and atopy later in life. Conversely, septic neonates are at
increased risk of impaired long-term neurodevelopment. While the positive effects
of antibiotics in the setting of infection are irrefutable, prolonged
administration of broad-spectrum, empiric antibiotics in neonates without
documented infection is associated with increased risk of LOS, necrotizing
enterocolitis, or death. Vaccines provide a unique opportunity to prevent
infection-associated disease; unfortunately, vaccinations have been largely
unsuccessful when administered in the first month of life with the exception of
vaccines against hepatitis B and tuberculosis. Future vaccines will require the
use of novel adjuvants to overcome this challenge. This review describes the
influence of infections, antibiotics, and vaccines during the first days of life,
as well as the influence on future health and disease. We will also discuss
potential immunomodulating therapies, which may serve to train the preterm immune
system and reduce subsequent infectious burden without subjecting neonates to the
risks accompanied by virulent pathogens.
PMID- 28690616
TI - Comparative Transcriptome Analysis Reveals Critical Function of Sucrose
Metabolism Related-Enzymes in Starch Accumulation in the Storage Root of Sweet
Potato.
AB - The starch properties of the storage root (SR) affect the quality of sweet potato
(Ipomoea batatas (L.) Lam.). Although numerous studies have analyzed the
accumulation and properties of starch in sweet potato SRs, the transcriptomic
variation associated with starch properties in SR has not been quantified. In
this study, we measured the starch and sugar contents and analyzed the
transcriptome profiles of SRs harvested from sweet potatoes with high, medium,
and extremely low starch contents, at five developmental stages [65, 80, 95, 110,
and 125 days after transplanting (DAP)]. We found that differences in both water
content and starch accumulation in the dry matter affect the starch content of
SRs in different sweet potato genotypes. Based on transcriptome sequencing data,
we assembled 112336 unigenes, and identified several differentially expressed
genes (DEGs) involved in starch and sucrose metabolism, and revealed the
transcriptional regulatory network controlling starch and sucrose metabolism in
sweet potato SRs. Correlation analysis between expression patterns and starch and
sugar contents suggested that the sugar-starch conversion steps catalyzed by
sucrose synthase (SuSy) and UDP-glucose pyrophosphorylase (UGPase) may be
essential for starch accumulation in the dry matter of SRs, and IbbetaFRUCT2, a
vacuolar acid invertase, might also be a key regulator of starch content in the
SRs. Our results provide valuable resources for future investigations aimed at
deciphering the molecular mechanisms determining the starch properties of sweet
potato SRs.
PMID- 28690617
TI - Transcriptomic Analysis of Soil Grown T. aestivum cv. Root to Reveal the Changes
in Expression of Genes in Response to Multiple Nutrients Deficiency.
AB - Deficiency of necessary macronutrients, i.e., Potassium (K), Magnesium (Mg),
Nitrogen (N), Phosphorus (P), and Sulfate (S) in the soil leads to a reduction in
plant growth and yield, which is a result of changes in expression level of
various genes. This study was performed to identify the differentially expressed
genes and its associated metabolic pathways occurred in soil grown wheat root
samples excavated from the control and treated fields. To identify the difference
in gene expression levels due to deficiency of the said nutrients, a
transcriptomic, meta-analysis was performed on array expression profile data. A
set of 435 statistically significant probes encoding 398 Nutrient Deficiency
Response Genes (NRGs) responding at-least one nutrients deficiency (ND) were
identified. Out of them 55 NRGs were found to response to minimum two ND.
Singular Enrichment Analysis (SEA) predicts ontological based classifications and
functional analysis of NRGs in different cellular/molecular pathways involved in
root development and growth. Functional annotation and reaction mechanism of
differentially expressed genes, proteins/enzymes in the different metabolic
pathway through MapMan analysis were explored. Further the meta-analysis was
performed to revels the active involvement each NRGs in distinct tissues and
their comparative potential expression analysis in different stress conditions.
The study results in exploring the role of major acting candidate genes such as
Non-specific serine/threonine protein kinase, Xyloglucan
endotransglucosylase/hydrolase, Peroxides, Glycerophosphoryl diester
phosphodiesterase, S-adenosylmethionine decarboxylase proenzyme, Dehydrin family
proteins, Transcription factors, Membrane Proteins, Metal binding proteins,
Photosystem proteins, Transporter and Transferase associated in different
metabolic pathways. Finally, the differences of transcriptional responses in the
soil-grown root of T. aestivum cv. and in-vitro grown model plants under
nutrients deficiency were summarized.
PMID- 28690618
TI - Identification of Major Effect QTLs for Agronomic Traits and CSSLs in Rice from
Swarna/Oryza nivara Derived Backcross Inbred Lines.
AB - Backcross inbred lines (BILs) derived from elite x wild crosses are very useful
for basic studies and breeding. The aim of this study was to map quantitative
trait loci (QTLs) associated with yield and related traits and to identify
chromosomal segment substitution lines (CSSLs) from unselected BC2F8 BILs of
Swarna/Oryza nivara IRGC81848. In all, 94 BILs were field evaluated in 2 years
(wet seasons, 2014 and 2015) for nine traits; days to 50% flowering, days to
maturity (DM), plant height (PH), number of tillers, number of productive
tillers, panicle weight, yield per plant, bulk yield, and biomass. BILs were
genotyped using 111 polymorphic simple sequence repeats distributed across the
genome. Fifteen QTLs including 10 novel QTLs were identified using composite
interval mapping, Inclusive composite interval mapping and multiple interval
mapping (MIM). O. nivara alleles were trait-enhancing in 26% of QTLs. Only 3 of
15 QTLs were also reported previously in BC2F2 of the same cross. These three
included the two major effect QTLs for DM and PH detected in both years with 13
and 20% phenotypic variance. Further, a set of 74 CSSLs was identified using CSSL
Finder and 22 of these showed significantly higher values than Swarna for five
yield traits. CSSLs, 220S for panicle weight and 10-2S with consistent high yield
in both years are worthy of large scale field evaluation. The major QTLs and 22
significantly different CSSLs are a useful resource for rice improvement and
dissecting yield related traits.
PMID- 28690619
TI - Characterization of Three L-Asparaginases from Maritime Pine (Pinus pinaster
Ait.).
AB - Asparaginases (ASPG, EC 3.5.1.1) catalyze the hydrolysis of the amide group of L
asparagine producing L-aspartate and ammonium. Three ASPG, PpASPG1, PpASPG2, and
PpASPG3, have been identified in the transcriptome of maritime pine (Pinus
pinaster Ait.) that were transiently expressed in Nicotiana benthamiana by
agroinfection. The three recombinant proteins were processed in planta to active
enzymes and it was found that all mature forms exhibited double activity
asparaginase/isoaspartyl dipeptidase but only PpASPG1 was able to catalyze
efficiently L-asparagine hydrolysis. PpASPG1 contains a variable region of 77
amino acids that is critical for proteolytic processing of the precursor and is
retained in the mature enzyme. Furthermore, the functional analysis of deletion
mutants demonstrated that this protein fragment is required for specific
recognition of the substrate and favors enzyme stability. Potassium has a limited
effect on the activation of maritime pine ASPG what is consistent with the lack
of a critical residue essential for interaction of cation. Taken together, the
results presented here highlight the specific features of ASPG from conifers when
compared to the enzymes from angiosperms.
PMID- 28690621
TI - Different Mutations Endowing Resistance to Acetyl-CoA Carboxylase Inhibitors
Results in Changes in Ecological Fitness of Lolium rigidum Populations.
AB - Various mutations altering the herbicide target site (TS), can lead to structural
modifications that decrease binding efficiency and results in herbicide resistant
weed. In most cases, such a mutation will be associated with ecological fitness
penalty under herbicide free environmental conditions. Here we describe the
effect of various mutations, endowing resistance to acetyl-CoA carboxylase
(ACCase) inhibitors, on the ecological fitness penalty of Lolium rigidum
populations. The TS resistant populations, MH (substitution of isoleucine 1781 to
leucine) and NO (cysteine 2088 to arginine), were examined and compared to a
sensitive population (AL). Grain weight (GW) characterization of individual
plants from both MH and NO populations, showed that resistant individuals had
significantly lower GW compared with sensitive ones. Under high temperatures,
both TS resistant populations exhibited lower germination rate as compared with
the sensitive (AL) population. Likewise, early vigor of plants from both TS
resistant populations was significantly lower than the one measured in plants of
the sensitive population. Under crop-weed intra-species competition, we found an
opposite trend in the response of plants from different populations. Relatively
to inter-population competition conditions, plants of MH population were less
affected and presented higher reproduction abilities compared to plants from both
AL and NO populations. On the basis of our results, a non-chemical approach can
be taken to favor the sensitive individuals, eventually leading to a decline in
resistant individuals in the population.
PMID- 28690620
TI - Sugarcane Water Stress Tolerance Mechanisms and Its Implications on Developing
Biotechnology Solutions.
AB - Sugarcane is a unique crop with the ability to accumulate high levels of sugar
and is a commercially viable source of biomass for bioelectricity and second
generation bioethanol. Water deficit is the single largest abiotic stress
affecting sugarcane productivity and the development of water use efficient and
drought tolerant cultivars is an imperative for all major sugarcane producing
countries. This review summarizes the physiological and molecular studies on
water deficit stress in sugarcane, with the aim to help formulate more effective
research strategies for advancing our knowledge on genes and mechanisms
underpinning plant response to water stress. We also overview transgenic studies
in sugarcane, with an emphasis on the potential strategies to develop superior
sugarcane varieties that improve crop productivity in drought-prone environments.
PMID- 28690622
TI - Nitrogen Metabolism in Adaptation of Photosynthesis to Water Stress in Rice Grown
under Different Nitrogen Levels.
AB - To investigate the role of nitrogen (N) metabolism in the adaptation of
photosynthesis to water stress in rice, a hydroponic experiment supplying with
low N (0.72 mM), moderate N (2.86 mM), and high N (7.15 mM) followed by 150 g?L-1
PEG-6000 induced water stress was conducted in a rainout shelter. Water stress
induced stomatal limitation to photosynthesis at low N, but no significant effect
was observed at moderate and high N. Non-photochemical quenching was higher at
moderate and high N. In contrast, relative excessive energy at PSII level (EXC)
was declined with increasing N level. Malondialdehyde and hydrogen peroxide
(H2O2) contents were in parallel with EXC. Water stress decreased catalase and
ascorbate peroxidase activities at low N, resulting in increased H2O2 content and
severer membrane lipid peroxidation; whereas the activities of antioxidative
enzymes were increased at high N. In accordance with photosynthetic rate and
antioxidative enzymes, water stress decreased the activities of key enzymes
involving in N metabolism such as glutamate synthase and glutamate dehydrogenase,
and photorespiratory key enzyme glycolate oxidase at low N. Concurrently, water
stress increased nitrate content significantly at low N, but decreased nitrate
content at moderate and high N. Contrary to nitrate, water stress increased
proline content at moderate and high N. Our results suggest that N metabolism
appears to be associated with the tolerance of photosynthesis to water stress in
rice via affecting CO2 diffusion, antioxidant capacity, and osmotic adjustment.
PMID- 28690623
TI - Achieving Lower Nitrogen Balance and Higher Nitrogen Recovery Efficiency Reduces
Nitrous Oxide Emissions in North America's Maize Cropping Systems.
AB - Few studies have assessed the common, yet unproven, hypothesis that an increase
of plant nitrogen (N) uptake and/or recovery efficiency (NRE) will reduce nitrous
oxide (N2O) emission during crop production. Understanding the relationships
between N2O emissions and crop N uptake and use efficiency parameters can help
inform crop N management recommendations for both efficiency and environmental
goals. Analyses were conducted to determine which of several commonly used crop N
uptake-derived parameters related most strongly to growing season N2O emissions
under varying N management practices in North American maize systems. Nitrogen
uptake-derived variables included total aboveground N uptake (TNU), grain N
uptake (GNU), N recovery efficiency (NRE), net N balance (NNB) in relation to GNU
[NNB(GNU)] and TNU [NNB(TNU)], and surplus N (SN). The relationship between N2O
and N application rate was sigmoidal with relatively small emissions for N rates
<130 kg ha-1, and a sharp increase for N rates from 130 to 220 kg ha-1; on
average, N2O increased linearly by about 5 g N per kg of N applied for rates up
to 220 kg ha-1. Fairly strong and significant negative relationships existed
between N2O and NRE when management focused on N application rate (r2 = 0.52) or
rate and timing combinations (r2 = 0.65). For every percentage point increase,
N2O decreased by 13 g N ha-1 in response to N rates, and by 20 g N ha-1 for NRE
changes in response to rate-by-timing treatments. However, more consistent
positive relationships (R2 = 0.73-0.77) existed between N2O and NNB(TNU),
NNB(GNU), and SN, regardless of rate and timing of N application; on average N2O
emission increased by about 5, 7, and 8 g N, respectively, per kg increase of
NNB(GNU), NNB(TNU), and SN. Neither N source nor placement influenced the
relationship between N2O and NRE. Overall, our analysis indicated that a careful
selection of appropriate N rate applied at the right time can both increase NRE
and reduce N2O. However, N2O reduction benefits of optimum N rate-by-timing
practices were achieved most consistently with management systems that reduced
NNB through an increase of grain N removal or total plant N uptake relative to
the total fertilizer N applied to maize. Future research assessing crop or N
management effects on N2O should include N uptake parameter measurements to
better understand N2O emission relationships to plant NRE and N uptake.
PMID- 28690624
TI - Transcriptome-Wide Identification of Novel UV-B- and Light Modulated Flavonol
Pathway Genes Controlled by VviMYBF1.
AB - Flavonols constitute a group of flavonoids with important photoprotective roles
in plants. In addition, flavonol content and composition greatly influences fruit
quality. We previously demonstrated that the grapevine R2R3-MYB transcription
factor (TF) VviMYBF1 promotes flavonol accumulation by inducing the expression of
flavonol synthase (VviFLS1/VviFLS4), a key step of the initial flavonol pathway.
Despite this, gene networks underlying flavonol modification in grapevine
including both structural and regulatory genes remain poorly understood. In order
to identify flavonol modifying genes and TFs acting downstream of VviMYBF1 a
microarray-based transcriptome analysis was performed on grapevine hairy roots
ectopically expressing VviMYBF1 or a Green Fluorescent Protein as control.
VviFLS1 was induced in VviMYBF1 transgenic roots and glycosylated flavonols
accumulated significantly compared with control lines. Among the differentially
expressed genes, potential flavonol-modifying enzymes with predicted
rhamnosyltransferase (e.g., RhaT1) or glycosyltransferase (e.g., GT3) activities
were identified. In addition, important TFs of the MYB and bZIP families such as
the proanthocyanidin regulator VviMYBPA1 and the UV-B light responsive HY5
homolog VviHYH were significantly altered in their expression pattern by
overexpression of VviMYBF1. Co-temporal expression analysis demonstrated positive
correlation of VviMYBF1 with VviFLS1, VviGT3, and VviRhaT1 during berry
development and in fruits ripened with different light and UV-B radiation
conditions at field. These results show that VviMYBF1 overexpression led to the
identification of novel genes of the flavonol pathway and that the flavonol
modifying machinery can be influenced by agricultural practices to optimize
flavonol composition in grapes.
PMID- 28690625
TI - Nitric Oxide Mediates Molybdenum-Induced Antioxidant Defense in Wheat under
Drought Stress.
AB - Molybdenum (Mo) has been reported to alleviate drought stress by enhancing
antioxidant defense in plants, but the underlying mechanism remains unclear.
Here, we hypothesized that Mo mediates nitric oxide (NO)-induced antioxidant
defense through Mo-enzymes, particularly by nitrate reductase (NR) in wheat under
drought stress. The 30-day-old wheat seedlings cultivated in -Mo (0 MUM Mo) and
+Mo (1 MUM Mo) Hoagland solutions were detached and then pretreated with Mo
enzyme inhibitors, NO scavengers, NO donors or their combinations according to
demands of complementary experiment under 10% polyethylene glycol 6000 (PEG)
stimulated drought stress (PSD). Mo supplementation increased the activities and
transcripts of antioxidant enzymes, decreased H2O2 and MDA contents, and elevated
NO production, implying that Mo-induced antioxidant defense may be related to NO
signal. Complementary experiment showed that NO production was induced by Mo,
while suppressed by Mo-enzyme inhibitors and NO scavengers, but restored by NO
donors, suggesting that Mo-induced increase of NO production may be due to the
regulation by Mo-enzymes. Further experiment indicated that the increased
activities and transcripts of antioxidant enzymes induced by Mo were suppressed
by Mo-enzyme inhibitors and NO scavengers, and NO donors could eliminate their
suppressing effects. Moreover, Mo application increased NR activity and
inhibitors of Mo-enzymes inhibited NR activity in wheat leaves under PSD,
suggesting that NR might involve in the regulation of Mo-induced NO production.
These results clearly indicate that NO mediates Mo-induced antioxidant defense at
least partially through the regulation of NR.
PMID- 28690626
TI - Agronomic Evaluation of Sorghum Hybrids for Silage Production Cultivated in
Semiarid Conditions.
AB - The aim of this study was to study the agronomic traits of different Sorghum
bicolor (L.) Moench hybrids for silage productionin semiarid conditions. It was a
1-year evaluation conducted in a randomized block design with 24 treatments and
three replicates. The treatments were sorghum hybrids developed by the breeding
program of "Embrapa Milho e Sorgo" (Brazilian Agricultural Research Corporation).
The fresh matter yield (FMY) in the first cut varied from 22,643.56 to 44,033.15
kg/ha, with an average of 32,607.37 kg/ha, leading to the formation of two
groups. Similar results were observed for the dry matter yield (DMY), in which
the highest group yielded from 9,471.32 to 14,540.23 kg/ha dry matter (DM). For
plant regrowth, there was an increase in the number of stems and a decrease in
the amount of panicles. Two groups were formed for the accumulated dry matter
yield (ADMY), averaging 14,217.91 kg/ha; the highest group showed mean values of
18,003.00 to 14,221.94 kg/ha. The evaluated sorghum hybrids exhibited
satisfactory accumulated forage yields due to their high yield in regrowth, which
indicates that they are suitable for use in animal production systems in semi
arid regions.
PMID- 28690627
TI - Isothiocyanates, Nitriles, and Epithionitriles from Glucosinolates Are Affected
by Genotype and Developmental Stage in Brassica oleracea Varieties.
AB - Vegetables of the Brassica oleracea group, such as broccoli, cauliflower, and
cabbage, play an important role for glucosinolate consumption in the human diet.
Upon maceration of the vegetable tissue, glucosinolates are degraded
enzymatically to form volatile isothiocyanates, nitriles, and epithionitriles.
However, only the uptake of isothiocyanates is linked to the cancer-preventive
effects. Thus, it is of great interest to evaluate especially the isothiocyanate
formation. Here, we studied the formation of glucosinolates and their respective
hydrolysis products in sprouts and fully developed vegetable heads of different
genotypes of the five B. oleracea varieties: broccoli, cauliflower as well as
white, red, and savoy cabbages. Further, the effect of ontogeny (developmental
stages) during the head development on the formation of glucosinolates and their
respective hydrolysis products was evaluated at three different developmental
stages (mini, fully developed, and over-mature head). Broccoli and red cabbage
were mainly rich in 4-(methylsulfinyl)butyl glucosinolate (glucoraphanin),
whereas cauliflower, savoy cabbage and white cabbage contained mainly 2-propenyl
(sinigrin) and 3-(methylsulfinyl)propyl glucosinolate (glucoiberin). Upon
hydrolysis, epithionitriles or nitriles were often observed to be the main
hydrolysis products, with 1-cyano-2,3-epithiopropane being most abundant with up
to 5.7 MUmol/g fresh weight in white cabbage sprouts. Notably, sprouts often
contained more than 10 times more glucosinolates or their hydrolysis products
compared to fully developed vegetables. Moreover, during head development, both
glucosinolate concentrations as well as hydrolysis product concentrations changed
and mini heads contained the highest isothiocyanate concentrations. Thus, from a
cancer-preventive point of view, consumption of mini heads of the B. oleracea
varieties is recommended.
PMID- 28690628
TI - Comparison of Salt Tolerance in Soja Based on Metabolomics of Seedling Roots.
AB - Soybean is an important economic crop that is continually threatened by abiotic
stresses, especially salt stress. Wild soybean is an important germplasm resource
for the breeding of cultivated soybean. The root system plays a very important
role in plant salt tolerance. To explore the salt tolerance-related mechanisms
among Soja, we have demonstrated the seedling roots' growth and metabolomics in
wild soybean, semi-wild soybean, and cultivated soybean under two types of salt
stress by using gas chromatography-mass spectrometry. We characterized 47 kinds
of differential metabolites under neutral salt stress, and isoleucine, serine, l
allothreonine, glutamic acid, phenylalanine, asparagines, aspartic acid,
pentadecanoic acid, lignoceric acid, oleic acid, galactose, tagatose, d-arabitol,
dihydroxyacetone, 3-hydroxybutyric acid, and glucuronic acid increased
significantly in the roots of wild soybean seedlings. However, these metabolites
were suppressed in semi-wild and cultivated soybeans. Amino acid, fatty acid,
sugars, and organic acid synthesis and the secondary metabolism of antioxidants
increased significantly in the roots of wild soybean seedling. Under alkaline
salt stress, wild soybean contained significantly higher amounts of proline,
glutamic acid, aspartic acid, l-allothreonine, isoleucine, serine, alanine,
arachidic acid, oleic acid, cis-gondoic acid, fumaric acid, l-malic acid, citric
acid, malonic acid, gluconic acid, 5-methoxytryptamine, salicylic acid, and
fluorene than semi-wild and cultivated soybeans. Our study demonstrated that
carbon and nitrogen metabolism, and the tricarboxylic acid (TCA) cycle and
receiver operating characteristics (especially the metabolism of phenolic
substances) of the seedling roots were important to resisting salt stress and
showed a regular decreasing trend from wild soybean to cultivated soybean. The
metabolomics's changes were critical factors in the evolution of salt tolerance
among Soja. This study provides new insights into salt tolerance in soybean, and
presents quantitative parameters for a salt tolerant soybean breeding system,
which is conducive to the rational use and protection of wild soybean resources.
PMID- 28690629
TI - Genome-Wide Analysis of Simple Sequence Repeats in Bitter Gourd (Momordica
charantia).
AB - Bitter gourd (Momordica charantia) is widely cultivated as a vegetable and
medicinal herb in many Asian and African countries. After the sequencing of the
cucumber (Cucumis sativus), watermelon (Citrullus lanatus), and melon (Cucumis
melo) genomes, bitter gourd became the fourth cucurbit species whose whole genome
was sequenced. However, a comprehensive analysis of simple sequence repeats
(SSRs) in bitter gourd, including a comparison with the three aforementioned
cucurbit species has not yet been published. Here, we identified a total of
188,091 and 167,160 SSR motifs in the genomes of the bitter gourd lines 'Dali-11'
and 'OHB3-1,' respectively. Subsequently, the SSR content, motif lengths, and
classified motif types were characterized for the bitter gourd genomes and
compared among all the cucurbit genomes. Lastly, a large set of 138,727 unique in
silico SSR primer pairs were designed for bitter gourd. Among these, 71 primers
were selected, all of which successfully amplified SSRs from the two bitter gourd
lines 'Dali-11' and 'K44'. To further examine the utilization of unique SSR
primers, 21 SSR markers were used to genotype a collection of 211 bitter gourd
lines from all over the world. A model-based clustering method and phylogenetic
analysis indicated a clear separation among the geographic groups. The genomic
SSR markers developed in this study have considerable potential value in
advancing bitter gourd research.
PMID- 28690630
TI - Lack of S-RNase-Based Gametophytic Self-Incompatibility in Orchids Suggests That
This System Evolved after the Monocot-Eudicot Split.
AB - Self-incompatibility (SI) is found in approximately 40% of flowering plant
species and at least 100 families. Although orchids belong to the largest
angiosperm family, only 10% of orchid species present SI and have gametophytic SI
(GSI). Furthermore, a majority (72%) of Dendrobium species, which constitute one
of the largest Orchidaceae genera, show SI and have GSI. However, nothing is
known about the molecular mechanism of GSI. The S-determinants of GSI have been
well characterized at the molecular level in Solanaceae, Rosaceae, and
Plantaginaceae, which use an S-ribonuclease (S-RNase)-based system. Here, we
investigate the hypothesis that Orchidaceae uses a similar S-RNase to those
described in Rosaceae, Solanaceae, and Plantaginaceae SI species. In this study,
two SI species (Dendrobium longicornu and D. chrysanthum) were identified using
fluorescence microscopy. Then, the S-RNase- and SLF-interacting SKP1-like1 (SSK1)
like genes present in their transcriptomes and the genomes of Phalaenopsis
equestris, D. catenatum, Vanilla shenzhenica, and Apostasia shenzhenica were
investigated. Sequence, phylogenetic, and tissue-specific expression analyses
revealed that none of the genes identified was an S-determinant, suggesting that
Orchidaceae might have a novel SI mechanism. The results also suggested that
RNase-based GSI might have evolved after the split of monocotyledons (monocots)
and dicotyledons (dicots) but before the split of Asteridae and Rosidae. This is
also the first study to investigate S-RNase-based GSI in monocots. However,
studies on gene identification, differential expression, and segregation analyses
in controlled crosses are needed to further evaluate the genes with high
expression levels in GSI tissues.
PMID- 28690631
TI - BdVRN1 Expression Confers Flowering Competency and Is Negatively Correlated with
Freezing Tolerance in Brachypodium distachyon.
AB - Vernalization is an essential process by which many temperate plant species
acquire competence for flowering. Brachypodium distachyon is a model plant for
temperate grasses including many cool-season forage and turfgrasses and cereals.
Grasses with spring growth habit do not require vernalization for flowering and
are typically less winter hardy. Yet the connection between vernalization and
freezing tolerance remain unclear. The diverse requirement of vernalization for
flowering makes it an ideal choice for studying the relationship between
vernalization and freezing tolerance. Here, we isolated and analyzed the spatial
and temporal expression patterns of two vernalization related homologous genes,
BdVRN1 and BdVRN3 in Bd21, a non-vernalization-requiring accession, and Bd29-1,
an accession shown to be vernalization-requiring. We showed that expression of
BdVRN1 and BdVRN3 is independent of vernalization in Bd21, but is vernalization
dependent in Bd29-1. Moreover, vernalization-induced expression of BdVRN1 appears
to precede that of BdVRN3 in Bd29-1. Bd21 RNAi knockdown mutants for BdVRN1
conferred vernalization requirement for flowering, and reduced the expression of
BdVRN3. Both Bd29-1 and the BdVRN1 RNAi mutants of Bd21 exhibited reduced
freezing tolerance upon vernalization treatment. Cold-responsive genes BdCBF2,
BdCBF3, BdCBF5, BdCBF6, and BdDREB2A were all constitutively expressed at a high
level in the BdVRN1 RNAi mutants of Bd21. Taken together, our results suggest
that expression of BdVRN1 promotes flowering by upregulating BdVRN3, and gaining
the competency for flowering reduces freezing tolerance in Brachypodium.
PMID- 28690632
TI - Neuropsychological Differences Related to Age in Dementia with Lewy Bodies.
AB - BACKGROUND/AIMS: To examine the influence of age on neuropsychological
performances in dementia with Lewy bodies (DLB) and Alzheimer disease (AD)
patients. METHODS: We examined memory, executive, and visuo-constructional
performances in 202 DLB patients and 236 AD patients. We divided the subjects
into three age groups (65-74, 75-84, and 85-95 years old), and evaluated the
differences in neuropsychological performances. RESULTS: Recent memory in the DLB
group was significantly better than that in the age-matched AD group when
comparing the age groups 65-74 years and 75-84 years; however, memory impairment
in the DLB patients in the age group 85-95 years was comparable with that in the
age-matched AD patients. In contrast to recent memory, the other assessed
neuropsychological performances, such as visuospatial and executive functions,
showed no significant change in differences between the DLB and AD groups with
advancing age. CONCLUSION: Our study revealed that the nature of memory
impairment in DLB patients changes according to age. DLB patients in the young
old and old-old age groups showed significantly better memory performance than
the age-matched AD patients, whereas memory performance of the DLB patients in
the oldest-old age group was similar to that of the age-matched AD patients. This
may be associated with the increased rate of coexisting AD pathology in DLB
patients with older age.
PMID- 28690633
TI - How Do Community-Dwelling Persons with Alzheimer Disease Fall? Falls in the
FINALEX Study.
AB - BACKGROUND: People with dementia are at high risk for falls. However, little is
known of the features causing falls in Alzheimer disease (AD). Our aim was to
investigate how participants with AD fall. METHODS: In the FINALEX (Finnish
Alzheimer Disease Exercise Trial) study, participants' (n = 194) falls were
followed up for 1 year by diaries kept by their spouses. RESULTS: The most common
reason for falls (n = 355) was stumbling (n = 61). Of the falls, 123 led to
injuries, 50 to emergency department visits, and 13 to fractures. The
participants without falls (n = 103) were younger and had milder dementia than
those with 1 (n = 34) or >=2 falls (n = 57). Participants with a Mini Mental
State Examination score of around 10 points were most prone to fall. In adjusted
regression models, good nutritional status, good physical functioning, and use of
antihypertensive medication (incident rate ratio [IRR] 0.68, 95% confidence
interval [CI] 0.54-0.85) protected against falls, whereas fall history (IRR 2.71,
95% CI 2.13-3.44), osteoarthritis, diabetes mellitus, chronic obstructive
pulmonary disease, higher number of drugs, drugs with anticholinergic properties,
psychotropics, and opioids (IRR 4.27, 95% CI 2.92-6.24) were risk factors for
falls. CONCLUSIONS: Our study provides a detailed account on how and why people
with AD fall, suggesting several risk and protective factors.
PMID- 28690634
TI - Preventive Effect of Rifampicin on Alzheimer Disease Needs at Least 450 mg Daily
for 1 Year: An FDG-PET Follow-Up Study.
AB - BACKGROUND: Rifampicin was reported to inhibit amyloid-beta oligomerization and
tau hyperphosphorylation in mouse models and could serve as a promising available
medicine for the prevention of Alzheimer disease (AD). To examine whether
rifampicin has such preventive effects in humans, we retrospectively reviewed 18F
FDG-PET findings of elderly patients with mycobacterium infection treated with
rifampicin. METHODS: Forty nondemented elderly patients treated with rifampicin
for mycobacterium infections who showed AD-type hypometabolism were enrolled. The
hypometabolic patterns were evaluated with stereotaxic statistical analysis and
region of interest analysis. RESULTS: Before treatment, AD-type hypometa bolism
was observed in 12 patients. The FDG uptake in the posterior cingulate cortex
(PCC) was improved or stabilized in 6 patients after 12-month therapy (450
mg/day), whereas another 6 patients with 6-month therapy showed a decreased FDG
uptake in the PCC. In patients who underwent FDG-PET only after treatment, the
metabolic decline in the PCC was significantly milder in patients with >=12
months of rifampicin treatment than in those with 6 months of treatment. Multiple
regression analysis revealed that the dose of rifampicin and treatment duration
significantly influenced FDG uptake in the PCC. CONCLUSION: The preventive effect
of rifampicin depended on the dose and the treatment duration, and the effect
needs at least 450 mg daily for 1 year.
PMID- 28690635
TI - The Development of the Dementia Screening Battery-100: Instrument Presentation,
Reliability, and Construct Validity.
AB - BACKGROUND/AIM: The screening of dementia in non-Westerners has so far relied on
translations and adaptations of reputed instruments. Other efforts focused on
developing culturally appropriate tests or tests in touch with new developments
in the field. This study presents the rationale behind the construction of a new
dementia screening test: the Dementia Screening Battery-100 (DSB-100). METHODS:
The DSB-100 was administered to 46 demented individuals and 159 healthy matched
controls. All demented participants met the DSM-IV criteria for dementia. The
healthy controls showed no cognitive impairment and were independent in
activities of daily living. The DSB-100 was administered as part of a larger
neuropsychological assessment to collect additional indices on the severity of
patients' dementia, depression, and frontal dysfunctions. The same information
was used for comparisons with DSB-100 scores. RESULTS: Multiple regression
analysis suggested that age and education, but not the variable sex, are
essential in predicting cognitive performance. Construct validation yielded 4
factors, namely attention-visuospatial factors, memory, language, and executive
functions. The results showed that the DSB-100 has a high interrater reliability
and an acceptable overall internal homogeneity. CONCLUSION: These results
validate the DSB-100 and suggest its appropriateness for dementia screening in
Tunisian elderly and possibly elderly people from other cultures with
modifications to some subscales.
PMID- 28690636
TI - Forks on the Run: Can the Stalling of DNA Replication Promote Epigenetic Changes?
AB - Built of DNA polymerases and multiple associated factors, the replication fork
steadily progresses along the DNA template and faithfully replicates DNA. This
model can be found in practically every textbook of genetics, with the more
complex situation of chromatinized DNA in eukaryotes often viewed as a variation.
However, the replication-coupled disassembly/reassembly of chromatin adds
significant complexity to the whole replication process. During the course of
eukaryotic DNA replication the forks encounter various conditions and numerous
impediments. These include nucleosomes with a variety of post-translational
modifications, euchromatin and heterochromatin, differentially methylated DNA,
tightly bound proteins, active gene promoters and DNA loops. At such positions
the forks slow down or even stall. Dedicated factors stabilize the fork and
prevent its rotation or collapse, while other factors resolve the replication
block and facilitate the resumption of elongation. The fate of histones during
replication stalling and resumption is not well understood. In this review we
briefly describe recent advances in our understanding of histone turnover during
DNA replication and focus on the possible mechanisms of nucleosome
disassembly/reassembly at paused replication forks. We propose that replication
pausing provides opportunities for an epigenetic change of the associated locus.
PMID- 28690637
TI - Association between Gastric Cancer Risk and Serum Helicobacter pylori Antibody
Titers.
AB - BACKGROUND/AIMS: It is difficult to confirm the accurate cutoff value to diagnose
Helicobacter pylori (Hp) infection using commercial serology kits. It is reported
that there were many cases with present/past infection that even the serum Hp-IgG
antibody (HpAb) titers were below the cutoff value (e.g., 10 U/mL for E
Plate(r)), suggesting that we might overlook many gastric cancer (GC). We
investigated an association between gastric cancer risk and serum Helicobacter
pylori antibody titers. METHODS: We conducted a primary screening between 2014
and 2015. We performed gastroendoscopy if HpAb titers were >=3.0 U/mL (i.e., more
than measurable limit, E-Plate). These patients were divided into two groups:
HpAb = 3.0-9.9 U/mL ("negative-high" group) and HpAb >= 10 U/mL; cutoff value
("over-10 U/mL" group). Hp infection status was investigated, and the number of
GC patients was counted. RESULTS: Among the 3321 subjects in the primary
screening, 56.9% (1891/3321) showed HpAb titers >=3.0 U/mL; 1314 patients
underwent gastroendoscopy. Ten were GC. 421 patients were "negative-high" group;
two were GC. After evaluating 381 patients for Hp infection, 22.6%/60.6% was with
present/past infection among the "negative-high" group. CONCLUSION: We also found
a correlation between HpAb titers and Hp infection status. "Negative-high" group
has a risk of GC.
PMID- 28690638
TI - Fat-Soluble Vitamin Deficiency in Pediatric Patients with Biliary Atresia.
AB - OBJECTIVE: To analyze the levels of fat-soluble vitamins (FSVs) in pediatric
patients with biliary atresia (BA) before and after the Kasai procedure. METHODS:
Pediatric patients with obstructive jaundice were enrolled in this study. The FSV
levels and liver function before, 2 weeks after, and 1, 3, and 6 months after the
Kasai procedure were measured. RESULTS: FSV deficiency was more obvious in
patients with BA than in patients with other cholestatic liver diseases,
especially vitamin D deficiency. 25-Hydroxy vitamin D (25-(OH)D) deficiency was
more pronounced in younger patients before surgery. The 25-(OH)D level was
significantly higher in patients with than without resolution of jaundice 3
months after surgery. At 6 months after surgery, the 25-(OH)D level was
abnormally high at 8.76 ng/ml in patients with unresolved jaundice. CONCLUSIONS:
Preoperative FSV deficiency, particularly vitamin D deficiency, is common in
patients with BA. 25-(OH)D deficiency is more pronounced in younger children
before surgery. Postoperative FSV deficiency was still prevalent as shown by the
lower 25-(OH)D levels in patients with BA and unresolved jaundice. This required
long-term vitamin AD supplementation for pediatric patients with BA and
unresolved jaundice after surgery.
PMID- 28690639
TI - Laparoscopic Radical Cholecystectomy for Primary or Incidental Early Gallbladder
Cancer: The New Rules Governing the Treatment of Gallbladder Cancer.
AB - AIM: To evaluate the technical feasibility and oncologic safety of laparoscopic
radical cholecystectomy (LRC) for primary or incidental early gallbladder cancer
(GBC) treatment. METHODS: Articles reporting LRC for GBC were reviewed from the
first case reported in 2010 to 2015 (129 patients). 116 patients had a
preoperative diagnosis of gallbladder cancer (primary GBC). 13 patients were
incidental cases (IGBC) discovered during or after a laparoscopic
cholecystectomy. RESULTS: The majority of patients who underwent LRC were pT2
(62.7% GBC and 63.6% IGBC). Parenchyma-sparing operation with wedge resection of
the gallbladder bed or resection of segments IVb-V were performed principally.
Laparoscopic lymphadenectomy was carried out according to the reported depth of
neoplasm invasion. Lymph node retrieved ranged from 3 to 21. Some authors
performed routine sampling biopsy of the inter-aorto-caval lymph nodes (16b1
station) before the radical treatment. No postoperative mortality was documented.
Discharge mean day was POD 5th. 16 patients had post operative morbidities. Bile
leakage was the most frequent post-operative complication. 5 y-survival rate
ranged from 68.75 to 90.7 months. CONCLUSION: Laparoscopy can not be considered
as a dogmatic contraindication to GBC but a primary approach for early case (pT1b
and pT2) treatment.
PMID- 28690640
TI - WDR62 Regulates Early Neural and Glial Progenitor Specification of Human
Pluripotent Stem Cells.
AB - Mutations in WD40-repeat protein 62 (WDR62) are commonly associated with primary
microcephaly and other developmental cortical malformations. We used human
pluripotent stem cells (hPSC) to examine WDR62 function during human neural
differentiation and model early stages of human corticogenesis. Neurospheres
lacking WDR62 expression showed decreased expression of intermediate progenitor
marker, TBR2, and also glial marker, S100beta. In contrast, inhibition of c-Jun N
terminal kinase (JNK) signalling during hPSC neural differentiation induced
upregulation of WDR62 with a corresponding increase in neural and glial
progenitor markers, PAX6 and EAAT1, respectively. These findings may signify a
role of WDR62 in specifying intermediate neural and glial progenitors during
human pluripotent stem cell differentiation.
PMID- 28690641
TI - Prostate Cancer Stem Cell Markers Drive Progression, Therapeutic Resistance, and
Bone Metastasis.
AB - Metastatic or recurrent tumors are the primary cause of cancer-related death. For
prostate cancer, patients diagnosed with local disease have a 99% 5-year survival
rate; however, this 5-year survival rate drops to 28% in patients with metastatic
disease. This dramatic decline in survival has driven interest in discovering new
markers able to identify tumors likely to recur and in developing new methods to
prevent metastases from occurring. Biomarker discovery for aggressive tumor cells
includes attempts to identify cancer stem cells (CSCs). CSCs are defined as tumor
cells capable of self-renewal and regenerating the entire tumor heterogeneity.
Thus, it is hypothesized that CSCs may drive primary tumor aggressiveness,
metastatic colonization, and therapeutic relapse. The ability to identify these
cells in the primary tumor or circulation would provide prognostic information
capable of driving prostate cancer treatment decisions. Further, the ability to
target these CSCs could prevent tumor metastasis and relapse after therapy
allowing for prostate cancer to finally be cured. Here, we will review potential
CSC markers and highlight evidence that describes how cells expressing each
marker may drive prostate cancer progression, metastatic colonization and growth,
tumor recurrence, and resistance to treatment.
PMID- 28690642
TI - Breakthrough attacks in patients with hereditary angioedema receiving long-term
prophylaxis are responsive to icatibant: findings from the Icatibant Outcome
Survey.
AB - BACKGROUND: Patients with hereditary angioedema (HAE) due to C1-inhibitor
deficiency (C1-INH-HAE) experience recurrent attacks of cutaneous or submucosal
edema that may be frequent and severe; prophylactic treatments can be prescribed
to prevent attacks. However, despite the use of long-term prophylaxis (LTP),
breakthrough attacks are known to occur. We used data from the Icatibant Outcome
Survey (IOS) to evaluate the characteristics of breakthrough attacks and the
effectiveness of icatibant as a treatment option. METHODS: Data on LTP use,
attacks, and treatments were recorded. Attack characteristics, treatment
characteristics, and outcomes (time to treatment, time to resolution, and
duration of attack) were compared for attacks that occurred with versus without
LTP. RESULTS: Data on 3228 icatibant-treated attacks from 448 patients with C1
INH-HAE were analyzed; 30.1% of attacks occurred while patients were using LTP.
Attack rate, attack severity, and the distribution of attack sites were similar
across all types of LTP used, and were comparable to the results found in
patients who did not receive LTP. Attacks were successfully treated with
icatibant; 82.5% of all breakthrough attacks were treated with a single icatibant
injection without C1-INH rescue medication. Treatment outcomes were comparable
for breakthrough attacks across all LTP types, and for attacks without LTP.
CONCLUSIONS: Patients who use LTP should be aware that breakthrough attacks can
occur, and such attacks can be severe. Thus, patients with C1-INH-HAE using LTP
should have emergency treatment readily available. Data from IOS show that
icatibant is effective for the treatment of breakthrough attacks. Trial
Registration NCT01034969.
PMID- 28690643
TI - Mechanism of resistance acquisition and treatment of macrolide-resistant
Mycoplasma pneumoniae pneumonia in children.
AB - Mycoplasma pneumoniae pneumonia (MPP) is one of the most common forms of
community-acquired pneumonia in children and adolescents. Outbreaks of MPP occur
in 3- to 7-year cycles worldwide; recent epidemics in Korea occurred in 2006
2007, 2011, and 2015-2016. Although MPP is known to be a mild, self-limiting
disease with a good response to macrolides, it can also progress into a severe
and fulminant disease. Notably, since 2000, the prevalence of macrolide-resistant
MPP has rapidly increased, especially in Asian countries, recently reaching up to
80%-90%. Macrolide-resistant Mycoplasma pneumoniae (MRMP) harbors a point
mutation in domain V of 23S rRNA with substitutions mainly detected at positions
2063 and 2064 of the sequence. The excessive use of macrolides may contribute to
these mutations. MRMP can lead to clinically refractory pneumonia, showing no
clinical or radiological response to macrolides, and can progress to severe and
complicated pneumonia. Refractory MPP is characterized by an excessive immune
response against the pathogen as well as direct injury caused by an increasing
bacterial load. A change of antibiotics is recommended to reduce the bacterial
load. Tetracyclines or quinolones can be alternatives for treating MRMP.
Otherwise, corticosteroid or intravenous immunoglobulin can be added to the
treatment regimen as immunomodulators to down-regulate an excessive host immune
reaction and alleviate immune-mediated pulmonary injury. However, the exact
starting time point, dose, or duration of immunomodulators has not been
established. This review focuses on the mechanism of resistance acquisition and
treatment options for MRMP pneumonia.
PMID- 28690644
TI - Individualized ibuprofen treatment using serial B-type natriuretic peptide
measurement for symptomatic patent ductus arteriosus in very preterm infants.
AB - PURPOSE: Plasma level of B-type natriuretic peptide (BNP), an emerging,
sensitive, and specific biomarker of hemodynamically significant patent ductus
arteriosus (PDA), rapidly decreases in infants receiving cyclooxygenase
inhibitors for ductal closure. We investigated the usefulness of serial BNP
measurement as a guide for individual identification of early constrictive
responses to ibuprofen in preterm infants with symptomatic PDA (sPDA). METHODS:
Before March 2010, the standard course of pharmacological treatment was initiated
with indomethacin (or ibuprofen) and routinely followed by 2 additional doses at
intervals of 24 hours. After April 2010, individualized pharmacological treatment
was used, starting with the first dose of ibuprofen and withholding additional
ibuprofen doses if the BNP concentration was <600 pg/mL and clinical symptoms of
PDA improved. RESULTS: The BNP-guided group received significantly fewer doses of
ibuprofen than the standard group did during the first course of treatment and
the entire study period. The need for further doses of cyclooxygenase inhibitors
and for surgical ligation was not significantly different between the 2 groups.
No significant differences were seen in clinical outcomes and/or complications
related to sPDA and/or pharmacological treatment. CONCLUSION: Individualized BNP
guided pharmacological treatment may be used clinically to avoid unnecessary
doses of cyclooxygenase inhibitors without increasing the ductal closure failure
and the short-term morbidity related to sPDA.
PMID- 28690645
TI - Neuroprotective effects of erythropoietin against hypoxic injury via modulation
of the mitogen-activated protein kinase pathway and apoptosis.
AB - PURPOSE: Hypoxic-ischemic encephalopathy is a significant cause of neonatal
morbidity and mortality. Erythropoietin (EPO) is emerging as a therapeutic
candidate for neuroprotection. Therefore, this study was designed to determine
the neuroprotective role of recombinant human EPO (rHuEPO) and the possible
mechanisms by which mitogen-activated protein kinase (MAPK) signaling pathway
including extracellular signal-regulated kinase (ERK1/2), JNK, and p38 MAPK is
modulated in cultured cortical neuronal cells and astrocytes. METHODS: Primary
neuronal cells and astrocytes were prepared from cortices of ICR mouse embryos
and divided into the normoxic, hypoxia (H), and hypoxia-pretreated with EPO
(H+EPO) groups. The phosphorylation of MAPK pathway was quantified using western
blot, and the apoptosis was assessed by caspase-3 measurement and terminal
deoxynucleotidyl transferase dUTP nick end labeling assay. RESULTS: All MAPK
pathway signals were activated by hypoxia in the neuronal cells and astrocytes
(P<0.05). In the neuronal cells, phosphorylation of ERK-1/-2 and apoptosis were
significantly decreased in the H+EPO group at 15 hours after hypoxia (P<0.05). In
the astrocytes, phosphorylation of ERK-1/-2, p38 MAPK, and apoptosis was reduced
in the H+EPO group at 15 hours after hypoxia (P<0.05). CONCLUSION: Pretreatment
with rHuEPO exerts neuroprotective effects against hypoxic injury reducing
apoptosis by caspase-dependent mechanisms. Pathologic, persistent ERK activation
after hypoxic injury may be attenuateed by pretreatment with EPO supporting that
EPO may regulate apoptosis by affecting ERK pathways.
PMID- 28690646
TI - Effects of lamotrigine on attention-deficit hyperactivity disorder in pediatric
epilepsy patients.
AB - PURPOSE: The purpose of this study was to investigate the effects of lamotrigine
for the treatment of attention-deficit hyperactivity disorder (ADHD) symptoms in
children with epilepsy. METHODS: Pediatric patients newly diagnosed with epilepsy
(n=90 [61 boys and 29 girls]; mean age, 9.1+/-3.4 years) were enrolled. All
patients were evaluated with the Korean ADHD rating scale (K-ARS)-IV before
treatment with lamotrigine and after doses had been administered. The mean
interval of ADHD testing was approximately 12.3 months. The initial dosage of
lamotrigine was 1 mg/kg/day (maximum 25 mg/day for the first 2 weeks), and
increased by 1 mg/kg every 2 weeks until titrated up to 7 mg/kg/day (or maximum
200 mg/day). RESULTS: The mean ADHD test score of the 90 subjects was 17.0+/-1.8
at baseline. It was slightly reduced to 15.6+/-1.7 after lamotrigine monotherapy
(P >0.01). Prior to treatment, a total of 31 patients (34.4%) met the diagnostic
criteria for ADHD according to Diagnostic and Statistical Manual of Mental
Disorders, 4th Edition, Text Revision, Of these 31 patients, 27 (87.1%) had
significantly improved ADHD scores with lamotrigine monotherapy (28.0+/-1.6
reduced to 18.1+/-2.6, P<0.001). Among these 27 patients, 25 (92.6%) showed
normalized electroencephalogram (EEG) and 26 (96.3%) achieved total freedom from
seizures within 12 months of the initiation of lamotrigine monotherapy.
CONCLUSION: The results from our study show that lamotrigine had a positive
effect in pediatric epilepsy patients by reducing ADHD symptoms, preventing
seizures, and normalizing EEG. However, further research is required to determine
whether lamotrigine is efficacious against ADHD symptoms independent of its
effects on epileptic seizures.
PMID- 28690647
TI - The evolution of electrocardiographic changes in patients with Duchenne muscular
dystrophies.
AB - PURPOSE: Myocardial dysfunction and dysrhythmias are inevitable consequences of
Duchenne muscular dystrophy. We aimed to evaluate specific trends of
electrocardiographic changes that reflect the progress of cardiomyopathy in
patients with Duchenne muscular dystrophy. METHODS: Fifty electrocardiograms
(ECGs) of 30 patients (ages 1 to 27 years) who had not been prescribed
medications for heart failure treatment at the time of examination were
retrospectively analyzed and compared with 116 ECGs of age-matched healthy 116
controls. Heart rate, leads with fragmented QRS (fQRS), corrected QT, Tpeak-to
Tend, and Tpeak-to-Tend/QT were analyzed. RESULTS: The patients with Duchenne
muscular dystrophy failed to show a normal age-related decline in heart rate but
showed an increasing trend in the prevalence of fQRS, corrected QT, corrected
Tpeak-to-Tend, and Tpeak-to-Tend/QT over time. In the <=10-year-old patient
group, a significant difference was found only in the prevalence of fQRS between
the patients and the controls. The prevalence of fQRS, heart rate, Tpeak-to
Tend/QT, and corrected Tpeak-to-Tend demonstrated significant differences between
the patients and the controls in the middle age group (11 to 15 years old). All
the indexes were statistically significantly different in the >=16-year-old
patient group. CONCLUSION: The prevalence of lead with fQRS representing regional
wall motion abnormalities was higher in the young patients than in the young
healthy controls, and this might be one of the first signs of myocardial change
in the patients. Markers of depolarization and repolarization abnormalities were
gradually prominent in the patients aged >10 years. Further studies are needed to
confirm these findings.
PMID- 28690648
TI - Recent Advances in the Neoadjuvant Treatment of Breast Cancer.
AB - In the last few decades, neoadjuvant therapy for breast cancer has gained
considerable therapeutic importance. Despite extensive clinical investigations,
it has not yet been clarified whether neoadjuvant therapy would result in
improved survival in comparison with the standard adjuvant setting in any
subgroups of patients with breast cancer. Chemotherapy is especially effective in
the treatment of endocrine insensitive tumors, and such ther-apeutic benefit can
be assumed for patients with triple-negative, or hormone receptor-negative and
human epidermal growth factor receptor 2 (HER2)-positive breast cancer. However,
dose escalation, modification of the therapeutic regimens according to early
tumor response, as well as the optimal sequence of administration are still
matters of debate. There is a current debate between clinical experts regarding
the concomitant and sequential administration of carboplatin and capecitabine,
respectively, as part of the standard neoadjuvant treatment, as well as the use
of bevacizumab, as part of the preoperative treatment. In case of HER2 positive
tumors, an anti-HER2 agent can be administered as part of the preoperative
treatment, and according to preliminary clinical data, dual HER2 blockade can
also be reasonable. Further, chemotherapy-free regimens can be justified in
highly endocrine sensitive tumors, while immune modulating agents may also gain
particular importance in the case of certain subtypes of breast cancer. Several
small-molecule targeted therapies are under clinical investigation and are
expected to provide new neoadjuvant treatment options. However, novel, more
predictive biomarkers are required for further evaluation of the neoadjuvant
therapies, as well as the effect of novel targeted agents intended to be
incorporated into neoadjuvant therapy.
PMID- 28690649
TI - Overexpression of Uridine-Cytidine Kinase 2 Correlates with Breast Cancer
Progression and Poor Prognosis.
AB - PURPOSE: Uridine-cytidine kinase (UCK) 2 is a rate-limiting enzyme involved in
the salvage pathway of pyrimidine-nucleotide biosynthesis. Recent studies have
shown that UCK2 is overexpressed in many types of cancer and may play a crucial
role in activating antitumor prodrugs in human cancer cells. In the current
study, we evaluated the potential prognostic value of UCK2 in breast cancer.
METHODS: We searched public databases to explore associations between UCK2 gene
expression and clinical parameters in patients with breast cancer. Gene set
enrichment analysis (GSEA) was performed to identify biological pathways
associated with UCK2 gene expression levels. Survival analyses were performed
using 10 independent large-scale breast cancer microarray datasets. RESULTS: We
found that UCK2 mRNA expression was elevated in breast cancer tissue compared
with adjacent nontumorous tissue or breast tissue from healthy controls. High
UCK2 levels were correlated with estrogen receptor negativity (p<0.001), advanced
tumor grade (p<0.001), and poor tumor differentiation (p<0.001). GSEA revealed
that UCK2-high breast cancers were enriched for gene sets associated with
metastasis, progenitor-like phenotypes, and poor prognosis. Multivariable Cox
proportional hazards regression analyses of microarray datasets verified that
high UCK2 gene expression was associated with poor overall survival in a dose
response manner. The prognostic power of UCK2 was superior to that of TNM staging
and comparable to that of multiple gene signatures. CONCLUSION: These findings
suggest that UCK2 may be a promising prognostic biomarker for patients with
breast cancer.
PMID- 28690650
TI - CD49f Can Act as a Biomarker for Local or Distant Recurrence in Breast Cancer.
AB - PURPOSE: Metastasis and local recurrence are the primary causes of treatment
failure and patient death in breast cancer. The aim of this study was to validate
a metastasis- and local recurrenceassociated biomarker for prognostic evaluation
and planning treatment strategies. METHODS: Formalin-fixed, paraffin-embedded
tissues from a cohort of 312 patients (all stage II and III) were used. The
prevalence of CD49f+ cells in the patients' tumors was analyzed and correlated
with clinical characteristics to determine its prognostic and clinical
implications. RESULTS: CD49f+ tumor cells were found in a minority of tumors,
with 62.8% of the samples showing not a single cell of this subtype. In the
clinical characteristics analysis, which were performed with t-tests, CD49f+
tumors were not associated with age, tumor size, World Health Organization grade,
nodal status, human epidermal growth factor receptor 2 status, progesterone
receptor status, or estrogen receptor status, although they were significantly
associated with disease recurrence (distant metastasis or/and local recurrence).
Univariate survival analysis using the Kaplan-Meier method showed that CD49f+
tumors were associated with markedly decreased disease-free survival (DFS); the
same result was found using multivariate Cox analysis, even when only
chemotherapy-treated patients were analyzed. CONCLUSION: Our results indicated
that breast tumors with CD49f+ cancer cells are associated with an increased risk
for disease recurrence after initial surgery with poor clinical outcomes
(decreased DFS). Therefore, as it requires testing for only one additional
protein, adding CD49f testing to conventional surgical pathology is a strategy
that has great potential for prognostic and treatment-guidance purposes.
PMID- 28690651
TI - Mutations of the Epidermal Growth Factor Receptor Gene in Triple-Negative Breast
Cancer.
AB - PURPOSE: Epidermal growth factor receptor (EGFR) is considered a potential
therapeutic target for anti-EGFR therapy in triple-negative breast cancer (TNBC).
However, the frequency of EGFR gene mutation in TNBC is low and varies with
ethnicity. This study aimed to investigate the incidence of EGFR gene mutation in
TNBC. METHODS: EGFR protein expression was evaluated by immunohistochemistry in
tissue microarrays of 493 TNBC cases using four different primary antibodies,
which included mutation-specific antibodies. For cases with an immunoreactivity
level >=1+, we performed pyrosequencing analysis for EGFR gene mutation. A case
was considered mutation-positive when its mutation frequency minus its limit of
detection (LOD) was >10%. Cases with mutation frequency higher than LOD were
assessed for EGFR gene mutation status using the Cobas assay and by peptide
nucleic acid-mediated polymerase chain reaction (PNA-clamping). RESULTS: Among
493 TNBCs, 148 (30.0%) exhibited staining >=1+ for EGFR, including 78 with 1+, 49
with 2+, and 21 with 3+. Positive EGFR expression (>=2+) was significantly
associated with lymphovascular invasion (p=0.010), but not with overall survival
(p=0.444) or disease-free survival (p=0.388). None of the 493 TNBCs harbored an
EGFR gene mutation. Among 148 cases with an EGFR staining result >=1+, five
(3.4%) showed mutation frequencies (4.4%-10.9%) higher than LOD (2.6%-4.3%) in
exons 19 (L747_P753>Q) or 21 (L858R and L861Q) as determined by pyrosequencing.
However, Cobas and PNA-clamping failed to detect the presence of EGFR gene
mutation in these five cases. CONCLUSION: No activating mutation of EGFR gene of
clinical significance was observed in 148 TNBC cases using three commercially
available methods. Thus, EGFR gene mutation appears to be an extremely rare event
in patients with TNBC.
PMID- 28690652
TI - Prognostic Impact of Progesterone Receptor Status in Chinese Estrogen Receptor
Positive Invasive Breast Cancer Patients.
AB - PURPOSE: Estrogen receptor (ER) and progesterone receptor (PR) have been used as
indicators of endocrine system status since the mid-1970s in the clinical
management of breast cancer. The predictive role of ER in endocrine therapy is
undisputed, but the prognostic value of PR is still debated. The aim of this
study was to investigate the clinical characteristics and prognosis of ER
positive breast cancer with different PR expression levels. METHODS: A population
cohort of 3,030 primary invasive ER positive breast cancer patients from a single
cancer center underwent surgery and received adjuvant endocrine therapy from 2004
to 2010. The clinical and biological features of these patients with high PR
expressing tumors were compared with those of patients with low PR-expressing
tumors. The follow-up data for disease-free survival (DFS), overall survival
(OS), and breast cancer specific survival (BCSS) was obtained from 2,778
patients. Cox regression analysis was used to correlate biomarkers and tumor
characteristics with DFS, OS, and BCSS. RESULTS: Tumors with low PR expression
had more invasive pathological features and biological indexes than those with
high PR expression. Low PR expression was an independent poor prognostic factor
for DFS (p=0.014; hazard ratio [HR], 0.781; 95% confidence interval [CI], 0.641
0.950), OS (p=0.002; HR, 0.699; 95% CI, 0.560-0.873), and BCSS (p=0.005; HR,
0.714; 95% CI, 0.566-0.902). Furthermore, in low PR expressing tumors, patients
who received chemotherapy had better DFS (p=0.002; HR, 0.449; 95% CI, 0.268
0.751), OS (p<0.001; HR, 0.341; 95% CI, 0.192-0.606), and BCSS (p<0.001; HR,
0.292; 95% CI, 0.156-0.549) than patients who did not received chemotherapy.
CONCLUSION: Patients with ER positive invasive breast cancer with low PR
expressing tumors have a worse prognosis than those with high PR expressing
tumors, and these patients can benefit from chemotherapy.
PMID- 28690653
TI - High Histologic Grade and High Ki-67 Expression Predict Phenotypic Alterations in
Node Metastasis in Primary Breast Cancers.
AB - PURPOSE: Several studies have shown that estrogen receptor (ER) and progesterone
receptor (PR) expression and human epidermal growth factor receptor 2 (HER2)
expression may vary during tumoral progression. We aimed to describe and compare
ER, PR, and HER2 expressions in primary breast tumors and synchronic axillary
nodal metastases, and evaluate phenotypic correlations between them. METHODS:
Patients were identified prospectively through surgical procedures between
September 2013 and July 2016. The status of ER, PR, HER2, and Ki-67 were
pathologically analyzed in breast cancers and axillary nodal metastases; these
patients were classified based on the breast cancer phenotypes into five
subgroups. RESULTS: Synchronic axillary nodal metastases were observed in 127
patients. In breast cancers and nodal metastases, correlation analyses of ER, PR,
and Ki-67 expression showed a statistical dependence and concordance between
these samples was unambiguously demonstrated through Bland-Altman plots for each
determination. Primary breast tumors were classified as follows: luminal A,
41.6%; luminal B, 40.0%; luminal B/HER2, 9.6%; HER2, 2.4%; triple negative, 6.4%.
Alterations in phenotype were observed in 28% of patients. The most frequent
phenotypic alteration was from luminal B to A (36.4%). Ten cases (30.3%) showed
alterations with therapeutic implications; six gained HER2 overexpression, and
four, hormonal receptor (HR) expression. A moderate strength of agreement
(Cohen's kappa coefficient, 0.59; 95% confidence interval, 0.48-0.71) was
observed. In multivariate analyses, high histologic grade (odds ratio [OR], 2.79;
p<0.047) and high Ki-67 expression (OR, 1.05; p<0.037) were independent factors
predictive of phenotypic alterations. CONCLUSION: Strong correlations were
observed in HR and Ki-67 expressions between primary breast tumors and axillary
nodal metastases, and a moderate concordance was observed in their phenotypical
characteristics. Nevertheless, alterations did exist, and one-third of these
changes may have therapeutic implications. The nodal metastases of tumors with
high grade and high Ki-67 expression may need to be analyzed, to obtain complete
therapeutic information.
PMID- 28690654
TI - The Usefulness of Intraoperative Circumferential Frozen-Section Analysis of
Lumpectomy Margins in Breast-Conserving Surgery.
AB - PURPOSE: Intraoperative frozen-section analysis of the lumpect-omy margin during
breast-conserving surgery (BCS) is an excellent method in obtaining a clear
resection margin. This study aimed to investigate the usefulness of
intraoperative circumferential frozen-section analysis (IOCFS) of lumpectomy
margin during BCS for breast cancer, and to find factors that increase the
conversion into mastectomy. METHODS: From 2007 to 2011, 509 patients with breast
cancer underwent IOCFS during BCS. The outer surfaces of the shaved lumpectomy
margins were evaluated. A negative margin was defined as no ink on the tumor. All
margins were evaluated using the permanent section analysis. RESULTS: Among the
509 patients, 437 (85.9%) underwent BCS and 72 (14.1%) finally underwent
mastectomy. Of the 483 pathologically confirmed patients, 338 (70.0%) were true
negative, 24 (5.0%) false-negative, 120 (24.8%) true-positive, and 1 (0.2%) false
positive. Twenty-four patients (4.7%) among total 509 patients had undetermined
margins as either atypical ductal hyperplasia or ductal carcinoma in situ in the
first IOCFS. The IOCFS has an accuracy of 94.8% with 83% sensitivity, 99.7%
specificity, 93.4% negative predictive value, and 99.2% positive predictive
value. Sixty-three cases (12.4%) were converted to mastectomy, the first
intraoperatively. Of the 446 (87.6%) patients who successfully underwent BCS, 64
patients received additional excisions and 32 were reoperated to achieve clear
margin (reoperation rate, 6.3%). Twenty-three of the reoperated patients
underwent re-excisions using the second intraoperative frozen section analysis,
and achieved BCS. Nine cases were additionally converted to mastectomy. No
significant differences in age, stage, and biological factors were found between
the BCS and mastectomy cases. Factors such as invasive lobular carcinoma,
multiple tumors, large tumor, and multiple excisions increased the conversion to
mastectomy. CONCLUSION: The IOCFS analysis during BCS is useful in evaluating
lumpectomy margins and preventing reoperation.
PMID- 28690655
TI - Screening Uptake Differences Are Not Implicated in Poorer Breast Cancer Outcomes
among Singaporean Malay Women.
AB - PURPOSE: This study was undertaken to examine the impact of screening and race on
breast cancer outcomes in Singapore. METHODS: An institutional database was
reviewed, and invasive ductal carcinoma (IDC) and ductal carcinoma in situ (DCIS)
data were analyzed separately. Overall survival (OS), disease-free survival
(DFS), and cancer-specific survival (CSS) were assessed. RESULTS: The study
included 6,180 IDC and 1,031 DCIS patients. The median follow-up time was 4.1
years. Among IDC patients, Malay women were the youngest when first diagnosed,
and were more likely to present with advanced stage disease. Malay women also had
the highest proportion of T3 and T4 tumors at 14.2%, compared with Chinese women
at 8.7% and Indian women at 9.6% (p<0.001). Malay women had a higher incidence of
node-positive disease at 58.3% compared with Chinese women at 46.4% and Indian
women at 54.9% (p<0.001). Malay subjects also had higher-grade tumors; 61.8% had
grade 3 tumors compared with 45.8% of Chinese women and 52% of Indian women
(p<0.001). Furthermore, tumors in Malay subjects were less endocrine-sensitive
and more human epidermal growth factor receptor 2 enriched. Malay women had the
lowest 5- and 10-year OS, DFS, and CSS rates (p<0.001). After separating
clinically and screen-detected tumors, multivariate analysis showed that race was
still significant for outcomes. For screen-detected tumors, the OS hazard ratio
(HR) for Malay women compared to Chinese women was 5.78 (95% confidence interval
[CI], 2.64-12.64), the DFS HR was 2.18 (95% CI, 1.19-3.99), and the CSS HR was
5.93 (95% CI, 2.15-16.39). For DCIS, there were no statistically significant
differences in the tumor size, grade, histology subtypes, or hormone sensitivity.
CONCLUSION: Malay race is a poor prognostic factor in both clinically and screen
detected IDC. Special attention should be given to the detection and follow-up of
breast cancer in this group.
PMID- 28690656
TI - Imaging Surveillance for Survivors of Breast Cancer: Correlation between Cancer
Characteristics and Method of Detection.
AB - PURPOSE: The aim of our study was to investigate the characteristics of primary
and recurrent breast cancers and the correlation between cancer subtypes and
detection modes. METHODS: Between 2003 and 2013, 147 cases of recurrent breast
cancer in 137 women (mean age, 45.30+/-10.78 years) were identified via an annual
clinical examination using radiological studies among 6,169 patients with a
breast cancer history (mean follow-up period, 13.26+/-1.78 years). Clinical,
radiological, and pathological findings including immunohistochemistry findings
of primary and recurrent cancers were reviewed. The size of the tumor in primary
and recurrent cancers, disease-free survival, methods of surgery, and the
recurrence detection modalities were analyzed with respect to the breast cancer
subtype. RESULTS: Ipsilateral and contralateral in-breast recurrence occurred in
105, 21 had axillary lymph node recurrence, and 21 had chest wall recurrences.
The subtypes of the primary cancers were hormone receptor (HR) positive and human
epidermal growth factor receptor 2 (HER2) negative (HR+HER2-) in 57, HER2
positive (HER2+) in 39, and triple-negative type in 51, and the recurrent cancers
in each subtype showed the same type as the primary cancer in 84.3% of cases. In
the in-breast recurrent cancers, the HR+HER2- cancers were most frequently
detected using ultrasonography (15/43) followed by mammography (MG) (11/43). The
HER2+ recurrent cancers were most commonly detected using MG (14/31, 45.2%),
whereas triple-negative type recurrent cancers most commonly presented as
symptomatic masses (15/31) (p=0.028). CONCLUSION: Most recurrent breast cancers
showed the same cancer subtype as the primary tumor, and recurrent breast cancer
subtypes correlated with the detection modality. Imaging surveillance of
survivors of breast cancer might be more beneficial in cases of HR+HER2- type
breast cancer or HER2+ type breast cancer than in cases of triple-negative type
breast cancer.
PMID- 28690657
TI - Epigenetic Silencing of MORT Is an Early Event in Cancer and Is Associated with
Luminal, Receptor Positive Breast Tumor Subtypes.
AB - Immortality is an essential characteristic of cancer cells; a recent
transcriptomic study of epithelial cell immortalization has linked epigenetic
silencing of the long noncoding RNA Mortal Obligate RNA Transcript (MORT; alias
ZNF667-AS1) to this process. This study evaluated the epigenetic and
transcriptional state of MORT in two premalignant conditions-ductal carcinomas in
situ and colon adenomas. Results show that MORT silencing is an early epigenetic
event in human carcinogenesis, likely occurring near the point where premalignant
cells gain immortality; this epigenetic silencing is maintained throughout
malignant transformation and metastatic growth. Additional associations between
MORT loss and clinical and molecular features of breast tumors showed that
silencing of MORT occurs predominantly in luminal, receptor-positive breast
cancer; is associated with overexpression of CCND1 and mutations of GATA3; and is
negatively correlated with TP53 mutations. Taken in toto, MORT silencing occurs
early in breast carcinogenesis, probably during cellular immortalization, and
precedes the development of invasive luminal breast cancer.
PMID- 28690658
TI - Influence of the Angelina Jolie Announcement and Insurance Reimbursement on
Practice Patterns for Hereditary Breast Cancer.
AB - Lack of awareness, the stigma of carrying a genetic mutation, and economic
factors are barriers to acceptance of BRCA genetic testing or appropriate risk
management. We aimed to investigate the influence of Angelina Jolie's
announcement of her medical experience and also health insurance reimbursement
for BRCA gene testing on practice patterns for hereditary breast and ovarian
cancer (HBOC). A survey regarding changes in practice patterns for HBOC before
and after the announcement was conducted online. The rate of BRCA gene testing
was obtained from the National Health Insurance Review and Assessment Service
database. From May to August 2016, 70 physicians responded to the survey. Genetic
testing recommendations and prophylactic management were increased after the
announcement. Risk-reducing salpingo-oophorectomy and contralateral prophylactic
mastectomy was significantly increased in BRCA carriers with breast cancer. The
BRCA testing rate increased annually. Health insurance and a celebrity
announcement were associated with increased genetic testing.
PMID- 28690659
TI - Chronic Myeloid Leukemia with a Complex Variant 'Ph' Translocation That Develops
in Breast Carcinoma, Postchemotherapy: A Rare but Treatable Entity.
AB - We report a case of chronic myeloid leukemia (CML) that developed after
postoperative chemotherapy with cyclophosphamide, doxorubicin and 5-fluorouracil
(CAF) for breast cancer. A 55-year-old woman was diagnosed with invasive ductal
carcinoma which was treated with a modified radical mastectomy followed by six
cycles of CAF chemotherapy. Nine years later, she developed CML and locoregional
recurrence. Her breast recurrence showed strong estrogen receptor, weak
progesterone receptor and strong human epidermal growth factor 2 (score 3+)
expression. Her secondary CML in the chronic phase showed a complex variant
translocation (CVT) involving chromosomes 9, 22, and 17. Considering that the
HER2/neu gene is also located on chromosome 17, this secondary CML in chronic
phase with CVT is indeed a rare occurrence. We discuss the associated genetic
factors and the possible role of breast cancer chemo/radiotherapy in the
development of such CML as well as its treatment and prognosis compared with de
novo CML.
PMID- 28690660
TI - A Case of Breast Cancer Brain Metastasis with a 16-Year Time Interval without
Evidence of Cancer Recurrence.
AB - The median time of brain metastasis from the diagnosis of breast cancer is
approximately 3 years. In this case report, a 69-year-old woman demonstrated
cerebellar ataxia. Brain magnetic resonance imaging revealed enhanced lesions in
bilateral cerebellar hemispheres. She had undergone surgery, radiation, and
chemotherapy for uterine and breast cancer 24 years prior and 16 years prior,
respectively. Although she had not received any anticancer treatment for 10
years, no recurrences were identified using whole body scans. A partial tumor
resection was performed and the histological diagnosis was an adenocarcinoma from
breast cancer. As no extracranial lesions were found, gamma-knife irradiation was
performed, without additional systemic chemotherapy. One month posttreatment, the
tumors dramatically reduced in size and the patient completely recovered from
cerebellar ataxia. Systemic chemotherapy is not always required for brain
metastasis from breast cancer with a long interval period, as long as no evidence
of extracranial recurrence is detected.
PMID- 28690661
TI - Reliability of the NICMAN Scale: An Instrument to Assess the Quality of
Acupuncture Administered in Clinical Trials.
AB - BACKGROUND: The aim of this study was to examine the reliability of a scale to
assess the methodological quality of acupuncture administered in clinical
research. METHODS: We invited 36 acupuncture researchers and postgraduate
students to participate in the study. Firstly, participants rated two articles
using the scale. Following this initial stage, modifications were made to scale
items and the exercise was repeated. Interrater reliability was assessed for
individual items using the Fleiss kappa statistic, whilst the overall scale used
the intraclass correlation coefficient statistic. A threshold agreement of >=0.61
was acceptable. RESULTS: We received 26 responses and a 72% response rate. The
first phase of testing found moderate reliability with intraclass correlation
coefficients of 0.46 and 0.55 for the articles. The interrater reliability of the
scales varied between and within the researchers (0.35, 0.60) and was more
consistent with the postgraduate students (0.54, 0.54). Five items on the scale
scored below the threshold and were revised for further testing. In this phase
the intraclass correlation coefficient demonstrated variability between articles
but improved to achieve reliability above the agreed threshold. CONCLUSION: This
study provides evidence of the reliability of the NICMAN scale although
improvements to a small number of items remain.
PMID- 28690662
TI - Parasite Killing of Leishmania (V) braziliensis by Standardized Propolis
Extracts.
AB - Treatments based on antimonials to cutaneous leishmaniasis (CL) entail a range of
toxic side effects. Propolis, a natural compound widely used in traditional
medical applications, exhibits a range of biological effects, including activity
against infectious agents. The aim of this study was to test the potential
leishmanicidal effects of different propolis extracts against Leishmania
(Viannia) braziliensis promastigotes and intracellular amastigotes in vitro.
Stationary-phase L. (V) braziliensis promastigotes were incubated with medium
alone or treated with dry, alcoholic, or glycolic propolis extract (10, 50, or
100 MUg/mL) for 96 h. Our data showed that all extracts exhibited a dose
dependent effect on the viability of L. (V) braziliensis promastigotes, while
controlling the parasite burden inside infected macrophages. Dry propolis extract
significantly modified the inflammatory profile of murine macrophages by
downmodulating TGF-beta and IL-10 production, while upmodulating TNF-alpha. All
three types of propolis extract were found to reduce nitric oxide and superoxide
levels in activated L. braziliensis-infected macrophages. Altogether, our results
showed that propolis extracts exhibited a leishmanicidal effect against both
stages of L. (V) braziliensis. The low cell toxicity and efficient microbicidal
effect of alcoholic or glycolic propolis extracts make them candidates to an
additive treatment for cutaneous leishmaniasis.
PMID- 28690663
TI - Huangqin-Tang and Ingredients in Modulating the Pathogenesis of Ulcerative
Colitis.
AB - Ulcerative colitis (UC) is the most common inflammatory bowel disease worldwide.
Current therapies in UC cause limitations, and herb medicine provides an
important choice for UC treatment. Huangqin-Tang (HQT) is a well-known classical
traditional Chinese herbal formula and has been used in China for thousands of
years. A large number of pharmacological studies demonstrated HQT and its
ingredients to be effective in treating UC. Though the therapeutic effect has
been evaluated, comprehensive up-to-date reviews in this field are not yet
available. Here we aim to review our current understanding of HQT and its
ingredients in treating UC and how the agents modulate the main pathogenesis of
the disease, including the intestinal environment, immune imbalance, inflammatory
pathways, and oxidative stress. The summary on this issue may provide better
understanding of HQT and its ingredients in treating UC and possibly help in
promoting its clinical application.
PMID- 28690664
TI - Chinese Herbal Medicine Meets Biological Networks of Complex Diseases: A
Computational Perspective.
AB - With the rapid development of cheminformatics, computational biology, and systems
biology, great progress has been made recently in the computational research of
Chinese herbal medicine with in-depth understanding towards pharmacognosy. This
paper summarized these studies in the aspects of computational methods,
traditional Chinese medicine (TCM) compound databases, and TCM network
pharmacology. Furthermore, we chose arachidonic acid metabolic network as a case
study to demonstrate the regulatory function of herbal medicine in the treatment
of inflammation at network level. Finally, a computational workflow for the
network-based TCM study, derived from our previous successful applications, was
proposed.
PMID- 28690666
TI - The duty to bring children living in conflict zones to a safe haven.
AB - In this paper, I will discuss a children's rights-based argument for the duty of
states, as a joint effort, to establish an effective program to help bring
children out of conflict zones, such as parts of Syria, and to a safe haven.
Children are among the most vulnerable subjects in violent conflicts who suffer
greatly and have their human rights brutally violated as a consequence.
Furthermore, children are also a group whose capacities to protect themselves are
very limited, while their chance to flee is most often only slim. I will then
discuss three counterarguments: the first counterargument would be that, instead
of getting the children out of a particular country, it would be better to
improve their situation in their home countries. A second counterargument could
be that those states, which have such a duty to bring children to a safe haven,
would be overburdened by it. Finally, the third counterargument I want to discuss
states that such a duty would also demand a military intervention, which could
worsen the situation even further.
PMID- 28690665
TI - Use of Integrative Medicine in the United States Military Health System.
AB - Integrative medicine (IM) is a model of care which uses both conventional and
nonconventional therapies in a "whole person" approach to achieve optimum mental,
physical, emotional, spiritual, and environmental health, and is increasingly
popular among patients and providers seeking to relieve chronic or multifactorial
conditions. The US Department of Defense (DoD) shows particular interest in and
usage of IM for managing chronic conditions including the signature "polytrauma
triad" of chronic pain, traumatic brain injury (TBI), and posttraumatic stress
disorder (PTSD) among its beneficiaries in the Military Health System (MHS).
These modalities range from conventional nondrug, nonsurgical options such as
cognitive-behavioral therapy to nonconventional options such as acupuncture,
chiropractic, and mind-body techniques. These are of particular interest for
their potential to relieve symptoms without relying on opiates, which impair
performance and show high potential for abuse while often failing to provide full
relief. This review describes the use of IM in the MHS, including definitions of
the model, common therapies and potential for use, and controversy surrounding
the practice. More research is needed to build a comprehensive usage analysis,
which in turn will inform sound clinical and financial practice for the MHS and
its beneficiaries.
PMID- 28690667
TI - Reclaiming reconciliation through community education for the Muslims and Tamils
of post-war Jaffna, Sri Lanka.
AB - This paper explores the possibilities and challenges for ethno-religious
reconciliation through secondary school education in post-war Sri Lanka, with a
specific focus on the Muslim and Tamil communities in the Northern city of
Jaffna. In doing so, we position our paper within the growing field of
'education, conflict and emergencies' of which there has been a growing body of
literature discussing this contentious relationship. The paper draws from an
interdisciplinary and critical theoretical framework that aims to analyse the
role of education for peacebuilding, through a multi-scalar application of four
interconnected dimensions of social justice: redistribution, recognition,
representation and reconciliation (or 4 R's, Novelli, Lopes Cardozo and Smith,
2015). We apply this framework to interpret primary data collected through an
ethnographic study of two under-studied communities that have been
disproportionately affected by the 1983 to 2009 civil war and displacement: the
Northern Sri Lankan Muslims and Northern Sri Lankan Tamils. We find that
structural inequalities in society are replicated in formal secondary school
education and are perceived to be perpetuating ethno-religious conflict between
Muslim and Tamil; second, through a multi-scalar analysis, formal peace education
is perceived by respondents not to be meeting the needs of communities; and
third, we observe how in response to failings of state peace education, an
'unofficial' Tamil-Muslim community education incorporating a social justice
based approach has emerged. This has facilitated a process of cross-community
reconciliation between Muslim and Tamil through individual (teachers, students)
and community (Muslim-Tamil community based organisations) agency. The paper
concludes by offering suggestions for peace education policy and future research.
PMID- 28690668
TI - White opioids: Pharmaceutical race and the war on drugs that wasn't.
AB - The US 'War on Drugs' has had a profound role in reinforcing racial hierarchies.
Although Black Americans are no more likely than Whites to use illicit drugs,
they are 6-10 times more likely to be incarcerated for drug offenses. Meanwhile,
a very different system for responding to the drug use of Whites has emerged.
This article uses the recent history of White opioids - the synthetic opiates
such as OxyContin(r) that gained notoriety starting in the 1990s in connection
with epidemic prescription medication abuse among White, suburban and rural
Americans and Suboxone(r) that came on the market as an addiction treatment in
the 2000s - to show how American drug policy is racialized, using the lesser
known lens of decriminalized White drugs. Examining four 'technologies of
whiteness' (neuroscience, pharmaceutical technology, legislative innovation and
marketing), we trace a separate system for categorizing and disciplining drug use
among Whites. This less examined 'White drug war' has carved out a less punitive,
clinical realm for Whites where their drug use is decriminalized, treated
primarily as a biomedical disease, and where their whiteness is preserved,
leaving intact more punitive systems that govern the drug use of people of color.
PMID- 28690669
TI - Establishment of integrated protocols for automated high throughput kinetic
chlorophyll fluorescence analyses.
AB - BACKGROUND: Automated plant phenotyping has been established as a powerful new
tool in studying plant growth, development and response to various types of
biotic or abiotic stressors. Respective facilities mainly apply non-invasive
imaging based methods, which enable the continuous quantification of the dynamics
of plant growth and physiology during developmental progression. However,
especially for plants of larger size, integrative, automated and high throughput
measurements of complex physiological parameters such as photosystem II
efficiency determined through kinetic chlorophyll fluorescence analysis remain a
challenge. RESULTS: We present the technical installations and the establishment
of experimental procedures that allow the integrated high throughput imaging of
all commonly determined PSII parameters for small and large plants using kinetic
chlorophyll fluorescence imaging systems (FluorCam, PSI) integrated into
automated phenotyping facilities (Scanalyzer, LemnaTec). Besides determination of
the maximum PSII efficiency, we focused on implementation of high throughput
amenable protocols recording PSII operating efficiency (PhiPSII). Using the
presented setup, this parameter is shown to be reproducibly measured in
differently sized plants despite the corresponding variation in distance between
plants and light source that caused small differences in incident light
intensity. Values of PhiPSII obtained with the automated chlorophyll fluorescence
imaging setup correlated very well with conventionally determined data using a
spot-measuring chlorophyll fluorometer. The established high throughput operating
protocols enable the screening of up to 1080 small and 184 large plants per hour,
respectively. The application of the implemented high throughput protocols is
demonstrated in screening experiments performed with large Arabidopsis and maize
populations assessing natural variation in PSII efficiency. CONCLUSIONS: The
incorporation of imaging systems suitable for kinetic chlorophyll fluorescence
analysis leads to a substantial extension of the feature spectrum to be assessed
in the presented high throughput automated plant phenotyping platforms, thus
enabling the simultaneous assessment of plant architectural and biomass-related
traits and their relations to physiological features such as PSII operating
efficiency. The implemented high throughput protocols are applicable to a broad
spectrum of model and crop plants of different sizes (up to 1.80 m height) and
architectures. The deeper understanding of the relation of plant architecture,
biomass formation and photosynthetic efficiency has a great potential with
respect to crop and yield improvement strategies.
PMID- 28690670
TI - Sparse Representation Based Multi-Instance Learning for Breast Ultrasound Image
Classification.
AB - We propose a novel method based on sparse representation for breast ultrasound
image classification under the framework of multi-instance learning (MIL). After
image enhancement and segmentation, concentric circle is used to extract the
global and local features for improving the accuracy in diagnosis and prediction.
The classification problem of ultrasound image is converted to sparse
representation based MIL problem. Each instance of a bag is represented as a
sparse linear combination of all basis vectors in the dictionary, and then the
bag is represented by one feature vector which is obtained via sparse
representations of all instances within the bag. The sparse and MIL problem is
further converted to a conventional learning problem that is solved by relevance
vector machine (RVM). Results of single classifiers are combined to be used for
classification. Experimental results on the breast cancer datasets demonstrate
the superiority of the proposed method in terms of classification accuracy as
compared with state-of-the-art MIL methods.
PMID- 28690671
TI - Association between the blood concentrations of ammonia and carnitine/amino acid
of schizophrenic patients treated with valproic acid.
AB - BACKGROUND: Administration of valproic acid (VPA) is complicated with
approximately 0.9% of patients developing hyperammonemia, but the pathogenesis of
this adverse effect remains to be clarified. The aim of the present study was to
search for mechanisms associated with VPA-induced hyperammonemia in the light of
changes in serum amino acids concentrations associated with the urea cycle of
schizophrenic patients. METHOD: Blood samples (10 mL) were obtained from 37
schizophrenic patients receiving VPA for the prevention of violent behaviors in
the morning after overnight fast. Blood concentrations of ammonia, VPA, free
carnitine, acyl-carnitine, and 40 amino acids including glutamate and citrulline
were measured for each patient. Univariate and multivariate regression analyses
were performed to identify amino acids or concomitantly administered drugs that
were associated with variability in the blood concentrations of ammonia. RESULT:
The blood ammonia level was positively correlated with the serum glutamate
concentration (r = 0.44, p < 0.01) but negatively correlated with glutamine (r =
0.41, p = 0.01), citrulline (r = -0.42, p = 0.01), and glycine concentrations (r
= -0.54, p < 0.01). It was also revealed that the concomitant administration of
the mood stabilizers (p = 0.04) risperidone (p = 0.03) and blonanserin (p < 0.01)
was positively associated with the elevation of the blood ammonia level.
CONCLUSION: We hypothisized that VPA would elevate the blood ammonia level of
schizophrenic patients. The observed changes in serum amino acids are compatible
with urea cycle dysfunction, possibly due to reduced carbamoyl-phosphate synthase
1 (CPS1) activity. We conclude that VPA should be prudently prescribed to
schizophrenic patients, particularly those receiving mood stabilizers or certain
antipsychotics.
PMID- 28690672
TI - Emulsified omega-3 fatty-acids modulate the symptoms of depressive disorder in
children and adolescents: a pilot study.
AB - BACKGROUND: The prevalence of mood disorders in children is a growing global
concern. Omega-3 fatty acids (FA) are emerging as a promising adjuvant therapy
for depressive disorder (DD) in paediatric patients. The primary objective of
this pilot, single-centre, randomized, double-blind controlled study was to
compare the efficacy of an Omega-3 FA fish oil emulsion with a control oil
emulsion alongside standard treatment for depressive symptoms in children and
adolescents suffering from depressive disorder (DD) and mixed anxiety depressive
disorder (MADD). METHODS: 38 children (12 patients were treated and diagnosed for
at least 1 month before enrolment, 26 patients were first-time diagnosed as DD)
aged 11-17 years were randomised 1:1 to the intervention (Omega-3 FA, 19
patients) or active comparator (Omega-6 FA, 19 patients) groups. Children's
depression inventory (CDI) ratings were performed at baseline, every 2 weeks for
a 12-week intervention period and at 4-week post-intervention. 35 patients (17 in
Omega-3 and 18 in Omega-6 groups) who completed the whole intervention period
were evaluated. Patients from Omega-3 group were stratified according to
diagnosis into two subgroups (DD-10/17 and mixed anxiety depressive disorder
(MADD)-7/17 patients) and in the Omega-6 group into DD-10/18 and MADD-8/18
patients. Groups were evaluated separately. Differences between-groups were
tested with the Student's t test or non-parametric Mann-Whitney U test. Two-way
ANOVA with repeated measures and Friedman test were used to analyse the Treatment
effect for response in CDI score. p < 0.05 was considered significant in all
statistical analyses. RESULTS: Significant reductions in CDI scores in 35
analysed patients who completed 12 weeks intervention were observed after 12
weeks of intervention only in the Omega-3 group (p = 0.034). After stratification
to depressive disorder and mixed anxiety depressive disorder subgroups, the DD
subgroup receiving the Omega-3 FA fish oil showed statistically greater
improvement (score reduction after 8 week treatment of -9.1 CDI, p = 0.0001) when
compared to the MADD subgroup (score reduction after 8 week treatment -4.24 CDI,
p = 0.271). CONCLUSIONS: CDI scores were reduced in the Omega-3 group and the
depression subgroup had greater improvement than the mixed depressive/anxiety
group. An Omega-3 fatty acid rich fish oil emulsion may be an effective adjuvant
supplement during the treatment of depressive disorders in children. Trial
registration ISRCTN81655012.
PMID- 28690673
TI - Professor Umberto Veronesi: a physician, a researcher, a brilliant man.
AB - Many of those who work in oncology or deal with cancer patients know of Prof.
Umberto Veronesi and none of them could deny the importance of his battle against
cancer. He devoted his life to improving cancer treatment and quality of life for
patients. He was a physician, and a politician, but above all he was a
researcher. He embodied the true spirit of research, i.e., to believe in
something and investigate every aspect of it until all the questions about it
have been satisfactorily answered. He never gave up when faced with challenges,
and he never stopped being curious. He believed in science, because he wanted to
believe in the future. He mixed scientific knowledge with human warmth and was
the pioneer of many breast cancer innovations. From the beginning of Prof.
Veronesi's career, his mission was clear: 'My first decision was to focus on the
fight against cancer. When I started at the National Cancer Institute in Milan, I
felt a profound sense of rebellion against the surrender of doctors and patients
to a disease that caused intense suffering. In particular, I could not stand the
havoc of a woman's body after a mastectomy: in order to remove just a small
breast cancer, not only the breast was taken away from the body, but also the
axillary lymph nodes and the chest muscles. Consequently, I decided to fight
mainly against breast cancer. It was a tough war: the dogma of mastectomy was so
deeply-rooted that everybody thought I was crazy when I suggested conservative
breast surgery.'.
PMID- 28690674
TI - The Veronesi quadrantectomy: an historical overview.
AB - Following a clinical trial in which the Halsted mastectomy was compared to the
less invasive quadrantectomy, no differences were reported in terms of local
recurrence, disease-free or overall survival between the two. As a result,
Umberto Veronesi was the first in the world to state that the radical mastectomy
appeared to involve unnecessary mutilation in patients with breast cancer of less
than 2 cm and no palpable axillary nodes. To date, the Veronesi quadrantectomy is
routinely considered for breast cancer treatment. This brief review, which
highlights the main advances over the last 50 years, is dedicated to Professor
Umberto Veronesi.
PMID- 28690675
TI - Development of sentinel node biopsy, ROLL and IART in early breast cancer at the
European Institute of Oncology, Milan (IEO).
AB - The problem of unnecessary axillary clearance in many patients with early breast
cancer was certainly a major issue at IEO when we started working with Prof.
Umberto Veronesi in 1994. At that time, axillary dissection in EBC was offered to
all patients and this procedure was often hotly debated during our
multidisciplinary breast cancer meetings. The question as to whether we could
avoid axillary dissection by using PET scans or other nuclear medicine methods
was frequently asked by Veronesi. This eventually prompted us to investigate
whether, as for melanoma patients, the sentinel node biopsy (SNB) approach could
reliably be applied to breast cancer. In December 1995, we proposed a new
lymphoscintigraphy protocol to detect the SN in early breast cancer patients to
our Ethic Committee, and it was approved. The pilot study was published in 1997
and after only 6 years, the first randomised trial comparing SNB and axillary
clearance in breast cancer patients was published. During the pilot study, we
optimised the lymphoscintigraphy technique by comparing different radiotracers
and different injection modalities. Following the observation that the majority
of the radiocolloids injected into the tumour did not migrate to lymph nodes, a
new method called ROLL or Radio-guided Occult Lesion Localisation was developed
for the localisation of non-palpable breast lesions. This technique was
introduced into clinical practice at the European Institute of Oncology in 1996.
Several studies showed that the ROLL procedure enabled the surgeon to remove non
palpable breast lesions easily and accurately, overcoming some disadvantages of
other methods such as wire-guided localisation (WGL). In addition to SNB and
ROLL, other protocols such as the IART (intraoperative avidination for
radionuclide therapy)-ARTHE (avidinated radiotherapy) procedure were developed at
the IEO Nuclear Medicine Division during the period 1994-2013. I remember that
time as the most professionally productive of my career and it would not have
been possible without the help, suggestions and encouragement given to me by
Umberto Veronesi.
PMID- 28690676
TI - Radioguided localisation of non-palpable lesions of the breast in Costa Rica:
review of results of our first 800 patients in private practice.
AB - BACKGROUND: Surgical treatment of non-palpable breast lesions is controversial.
At the European Institute of Oncology in Milan, Italy, Prof Umberto Veronesi
introduced a new technique called the radioguided occult lesion localisation
(ROLL) in 1996 to replace conventional methods and their disadvantages (Zurrida
S, Galimberti V, and Monti S et al (1998) Radioguided localization of occult
breast lesionsBreast7 11-13 https://doi.org/10.1016/S0960-9776(98)90044-3). Given
the success experienced in that institution, the method became the technique of
choice for the early diagnosis of breast cancer. In this paper, we will examine
the technical aspects of ROLL and the results from a large series of patients
treated in our private practice in Costa Rica. METHODS: We analysed the first 816
patients with different non-palpable breast lesions detected by ultrasound or
mammography within our private practice in Costa Rica. In 774 patients,
technetium 99m labelled with human serum albumin (7-10 MBq) in 0.2 ml of saline
solution was injected into the lesion under mammographic or ultrasound guidance.
The excisional biopsy was done by means of a gamma-probe and complete excision of
the lesion was verified by X-ray on the specimen in lesions that were visible by
mammography and ultrasound 4 months after surgery. In the remaining 42 patients,
the localisation of the lesion was carried out by wire. RESULTS: The tracer was
correctly positioned in the first attempt in 772/816 (94.6%) of cases and in the
second attempt in two other cases. In 42/816 (5.1%) cases, the localisation of
the lesion had to be performed with the traditional method. X-rays showed that
the lesion was entirely removed in 770/772 (99.74%) of cases. CONCLUSION: The
ROLL is a simple and excellent option for the removal of hidden breast lesions in
clinical practice. It offers the advantage of making resections safer and with
tumour-free margins, in addition to reducing the number of reinterventions. Since
it makes it possible to specify to the pathologist the exact site where the
lesion is located, we can guarantee a better diagnosis. The rate of success with
the use of this technique corresponds to the available scientific data, so we
conclude that it is a procedure that we can routinely perform in private practice
in Costa Rica.
PMID- 28690677
TI - The past and future of breast cancer treatment-from the papyrus to individualised
treatment approaches.
AB - Cancer is one of the oldest diseases ever described, since ancient Egypt there
have always been attempts to treat and cure this illness. The growing body of
knowledge about breast cancer biology and improvements in surgical and medical
treatments has been built over time with contributions from many talented and
enthusiastic physicians and researchers. Medical advances have changed the
approach from a previously incurable condition, into a surgical disease. Further
improvements in cancer biology have allowed the development of systemic
treatments, hormonal therapies, and targeted drugs. The description of the
molecular intrinsic subtypes of breast cancer clarified the understanding of
breast cancer as a group of heterogeneous diseases, associated with different
clinical outcomes, and therapeutic opportunities. This paper reviews how breast
cancer treatment has improved since the earliest descriptions, in ancient times,
and how future approaches, such as gene signatures, molecular profiling, and
liquid biopsies, aim to further develop individualised treatments and improve
treatment outcomes.
PMID- 28690678
TI - The molecular understanding of cancer: from the unspeakable illness to a curable
disease.
AB - The beginning of our understanding of the molecular basis of cancer and the
discovery in the 1980s of cancer associated genes, oncogenes, and tumour
suppressor genes has led to cancer becoming a treatable condition rather than an
unspeakable disease. In 1971, the then USA President, Richard Nixon, declared
'war against cancer' with a far too optimistic perspective of winning in just a
few years. This tactic failed because our knowledge of the disease was still very
limited and even its origin-viral or due to exposure to external agents-was still
highly debated. A better understanding of the cause(s) of the origin of cancer
led to its definition as a genetic disease at the somatic level and heralded a
new era for molecular diagnosis and the development of more mechanistic evidence
based, targeted cancer therapies. However, the initial positive results were soon
overshadowed by a major limitation of targeted agents, namely resistance
mechanisms, which still represent an obstacle for the full eradication of the
disease. More recently, effective therapeutic approaches have been developed in
the field of 'immunotherapy'. The combination of novel therapies will hopefully
result in effective cancer growth control and make the disease 'chronic'. The
launch of the 'Moonshot Cancer Program' by President Barack Obama aims to
significantly reduce cancer deaths in the next decade-let us see.
PMID- 28690679
TI - Trichoderma reesei complete genome sequence, repeat-induced point mutation, and
partitioning of CAZyme gene clusters.
AB - BACKGROUND: Trichoderma reesei (Ascomycota, Pezizomycotina) QM6a is a model
fungus for a broad spectrum of physiological phenomena, including plant cell wall
degradation, industrial production of enzymes, light responses, conidiation,
sexual development, polyketide biosynthesis, and plant-fungal interactions. The
genomes of QM6a and its high enzyme-producing mutants have been sequenced by
second-generation-sequencing methods and are publicly available from the Joint
Genome Institute. While these genome sequences have offered useful information
for genomic and transcriptomic studies, their limitations and especially their
short read lengths make them poorly suited for some particular biological
problems, including assembly, genome-wide determination of chromosome
architecture, and genetic modification or engineering. RESULTS: We integrated
Pacific Biosciences and Illumina sequencing platforms for the highest-quality
genome assembly yet achieved, revealing seven telomere-to-telomere chromosomes
(34,922,528 bp; 10877 genes) with 1630 newly predicted genes and >1.5 Mb of new
sequences. Most new sequences are located on AT-rich blocks, including 7
centromeres, 14 subtelomeres, and 2329 interspersed AT-rich blocks. The seven
QM6a centromeres separately consist of 24 conserved repeats and 37 putative
centromere-encoded genes. These findings open up a new perspective for future
centromere and chromosome architecture studies. Next, we demonstrate that sexual
crossing readily induced cytosine-to-thymine point mutations on both tandem and
unlinked duplicated sequences. We also show by bioinformatic analysis that T.
reesei has evolved a robust repeat-induced point mutation (RIP) system to
accumulate AT-rich sequences, with longer AT-rich blocks having more RIP
mutations. The widespread distribution of AT-rich blocks correlates genome-wide
partitions with gene clusters, explaining why clustering of genes has been
reported to not influence gene expression in T. reesei. CONCLUSION:
Compartmentation of ancestral gene clusters by AT-rich blocks might promote
flexibilities that are evolutionarily advantageous in this fungus' soil habitats
and other natural environments. Our analyses, together with the complete genome
sequence, provide a better blueprint for biotechnological and industrial
applications.
PMID- 28690680
TI - From grass to gas: microbiome dynamics of grass biomass acidification under
mesophilic and thermophilic temperatures.
AB - BACKGROUND: Separating acidification and methanogenic steps in anaerobic
digestion processes can help to optimize the process and contribute to producing
valuable sub-products such as methane, hydrogen and organic acids. However, the
full potential of this technology has not been fully explored yet. To assess the
underlying fermentation process in more detail, a combination of high-throughput
sequencing and proteomics on the acidification step of plant material (grass) at
both mesophilic and thermophilic temperatures (37 and 55 degrees C,
respectively) was applied for the first time. RESULTS: High-strength liquor from
acidified grass biomass exhibited a low biodiversity, which differed greatly
depending on temperature. It was dominated by Bacteroidetes and Firmicutes at 37
degrees C, and by Firmicutes and Proteobacteria at 55 degrees C. At the methane
stage, Methanosaeta, Methanomicrobium and Methanosarcina proved to be highly
sensitive to environmental changes as their abundance in the seed sludges dropped
dramatically after transferring the seed sludges from the respective reactors
into the experimental setup. Further, an increase in Actinobacteria coincided
with reduced biogas production at the end of the experiment. Over 1700 proteins
were quantified from the first cycle of acidification samples using label-free
quantitative proteome analysis and searching protein databases. The most abundant
proteins included an almost complete set of glycolytic enzymes indicating that
the microbial population is basically engaged in the degradation and catabolism
of sugars. Differences in protein abundances clearly separated samples into two
clusters corresponding to culture temperature. More differentially expressed
proteins were found under mesophilic (120) than thermophilic (5) conditions.
CONCLUSION: Our results are the first multi-omics characterisation of a two-stage
biogas production system with separated acidification and suggest that screening
approaches targeting specific taxa such as Methanosaeta, Methanomicrobium and
Methanosarcina could be useful diagnostic tools as indicators of environmental
changes such as temperature or oxidative stress or, as in the case of
Actinobacteria, they could be used as a proxy of the gas production potential of
anaerobic digesters. Metaproteome analyses only detected significant expression
differences in mesophilic samples, whereas thermophilic samples showed more
stable protein composition with an abundance of chaperones suggesting a role in
protein stability under thermal stress.
PMID- 28690681
TI - Modified technique of transforaminal lumbar interbody fusion for segmental
correction of lumbar kyphosis: a safe alternative to osteotomies?
AB - BACKGROUND: Sagittal rebalancing of a fixated lumbar hypolordosis (kyphosis) is
very important to gain satisfactory results. To correct a misalignment vertebral
column resection or pedicle subtraction osteotomies are favored, disregarding the
relatively high complication rates. The aim of this study was to evaluate the
efficiency and safety of a new modified transforaminal lumbar fusion technique as
an alternative. METHODS: We conducted a retrospective review (06/2011-06/2015 )
of a prospective database at an University hospital. Inclusion criteria were
adult patients with a fixated lumbar hypolordosis and the need of monosegmental
correction of more than 10 degrees with an mTLIF. Exclusion criteria consisted
of minor aged patients and polysegmental corrections. Study parameters were the
perioperative complications and the achieved postsurgical lordosis. The follow up
period was 6 months. RESULTS: A total of 11 patients could be included. The mean
segmental lordosis was -2.3 degrees +/- 12.4 degrees (range -22 degrees to 14
degrees ) preoperative and 15.5 degrees +/- 10.5 degrees (range 0 degrees to
29 degrees ) postoperative. The degree of correction was 17 degrees +/- 5.7
degrees in mean per treated segment (range 12 degrees to 29 degrees ). No
neurologic or vascular complications occurred. No substantial loss of correction
or implant failure was noted during the 6-month follow-up. CONCLUSION: The
modified transforaminal lumbar fusion technique is a safe method to correct a
fixated lumbar kyphosis. The potential of segmental correction is comparable to
pedicle subtraction osteotomies but sparing potentially healthy segments.
PMID- 28690682
TI - Autologous bone marrow-derived mononuclear cells transplantation in type 2
diabetes mellitus: effect on beta-cell function and insulin sensitivity.
AB - BACKGROUND: Insulin resistance and insulin deficiency are the cardinal defects in
the pathogenesis of type 2 diabetes mellitus (T2DM). Despite the plethora of anti
diabetic medications, drugs specifically targeting the beta-cells are still
desired. Stem cell therapy has emerged as a novel therapeutics strategy to target
beta-cells; however, their mechanism of action has not been well defined. This
study aims to examine the efficacy and safety of autologous bone marrow-derived
mononuclear cells (ABM-MNCs) transplantation in T2DM, and explores the
mechanistic insights into stem cells action through metabolic studies. METHODS:
Seven T2DM patients with the duration of disease >=5 years, receiving triple oral
anti-diabetic drugs along with insulin (>=0.4 IU per kg per day) and HbA1c <=
7.5% (<=58.0 mmol/mol) were enrolled for ABM-MNCs administration through a
targeted approach. The primary end-point was a reduction in insulin requirement
by >=50% from baseline, while maintaining HbA1c < 7.0% (<53.0 mmol/mol) with
improvement in insulin secretion, and/or insulin sensitivity after ABM-MNCs
transplantation. RESULTS: Six out of 7 (90%) patients achieved the primary end
point. At 6 months, there was a significant reduction in insulin requirement by
51% as compared to baseline (p < 0.003). This was accompanied by a significant
increase in the 2nd phase C-peptide response during hyperglycemic clamp (p =
0.018), whereas there were no significant alterations in insulin sensitivity and
glucose disposal rate during hyperinsulinemic-euglycemic clamp relative to the
baseline. Other measures of beta-cell indices like HOMA-beta, and stimulated C
peptide response to glucagon and mixed meal tolerance test were non-contributory.
CONCLUSION: ABM-MNCs transplantation results in significant reduction in insulin
doses and improvement in C-peptide response in patients with T2DM. Metabolic
studies may be more useful than conventional indices to predict beta-cell
function in patients with advanced duration of T2DM. Trial registration
Clinicaltrials.gov NCT01759823.
PMID- 28690683
TI - Microchip-based 3D-Cell Culture Using Polymer Nanofibers Generated by Solution
Blow Spinning.
AB - Polymer nano/micro fibers have found many applications including 3D cell culture
and the creation of wound dressings. The fibers can be produced by a variety of
techniques that include electrospinning, the primary disadvantage of which
include the requirement for a high voltage supply (which may cause issues such as
polymer denaturation) and lack of portability. More recently, solution blow
spinning, where a high velocity sheath gas is used instead of high voltage, has
been used to generate polymer fibers. In this work, we used blow spinning to
create nano/microfibers for microchip-based 3D cell culture. First, we thoroughly
investigated fiber generation from a 3D printed gas sheath device using two
polymers that are amenable to cell culture (polycaprolactone, PCL and
polystyrene, PS) as well as the parameters that can affect PCL and PS fiber
quality. Using the 3D printed sheath device, it was found that the pressure of
the sheath N2 and the concentration of polymer solutions determine if fibers can
be produced as well as the resulting fiber morphology. In addition, we showed how
these fibers can be used for 3D cell culture by directly depositing PCL fibers in
petri dishes and well plates. It is shown the fibers have good compatibility with
RAW 264.7 macrophages and the PCL fiber scaffold can be as thick as 178 +/- 14
MUm. PCL fibers created from solution blow spinning (with the 3D printed sheath
device) were then integrated with a microfluidic device for the first time to
fabricate a 3D cell culture scaffold with a flow component. After culturing and
stimulating macrophages on the fluidic device, it was found that the integrated
3D fibrous scaffold is a better mimic of the extracellular matrix (as opposed to
a flat, 2D substrate), with enhanced nitrite accumulation (product of nitric
oxide release) from macrophages stimulated with lipopolysaccharide. PS fibers
were also made and integrated in a microfluidic device for 3D culture of
endothelial cells, which stayed viable for at least 72 hours (48 hours under the
flowing conditions). This approach will be useful for future studies involving
more realistic microchip-based culture models for studying cell-to-cell
communication.
PMID- 28690684
TI - 4-Fluoroprolines: Conformational Analysis and Effects on the Stability and
Folding of Peptides and Proteins.
AB - Proline is unique among proteinogenic amino acids because a pyrrolidine ring
links its amino group to its side chain. This heterocycle constrains the
conformations of the main chain and thus templates particular secondary
structures. Proline residues undergo post-translational modification at the 4
position to yield 4-hydroxyproline, which is especially prevalent in collagen.
Interest in characterizing the effects of this modification led to the use of 4
fluoroprolines to enhance inductive properties relative to the hydroxyl group of
4-hydroxyproline and to eliminate contributions from hydrogen bonding. The strong
inductive effect of the fluoro group has three main consequences: enforcing a
particular pucker upon the pyrrolidine ring, biasing the conformation of the
preceding peptide bond, and accelerating cis/trans prolyl peptide bond
isomerization. These subtle, yet reliable modulations make 4-fluoroproline
incorporation a complement to traditional genetic approaches for exploring
structure-function relationships in peptides and proteins, as well as for
endowing peptides and proteins with conformational stability.
PMID- 28690685
TI - Examining for an association between candidate gene polymorphisms in the
metabolic syndrome components on excess weight and adiposity measures in youth: a
cross-sectional study.
AB - BACKGROUND: A polymorphism in a gene may exert its effects on multiple
phenotypes. The aim of this study is to explore the association of 10 metabolic
syndrome candidate genes with excess weight and adiposity and evaluate the effect
of perinatal and socioeconomic factors on these associations. METHODS: The
anthropometry, socioeconomic and perinatal conditions and 10 polymorphisms were
evaluated in 1081 young people between 10 and 18 years old. Genotypic
associations were calculated using logistic and linear models adjusted by age,
gender, and pubertal maturation, and a genetic risk score (GRS) was calculated by
summing the number of effect alleles. RESULTS: We found that AGT-rs699 and the
IRS2-rs1805097 variants were significantly associated with excess weight, OR =
1.25 (CI 95% 1.01-1.54; p = 0.034); OR = 0.77 (CI 95% 0.62-0.96; p = 0.022),
respectively. AGT-rs699 and FTO-rs17817449 variants were significantly and
directly associated with body mass index (BMI) (p = 0.036 and p = 0.031), while
IRS2-rs1805097 and UCP3-rs1800849 were significantly and negatively associated
with BMI and waist circumference, correspondingly. Each additional effect allele
in GRS was associated with an increase of 0.020 log(BMI) (p = 0.004). No effects
from the socioeconomic and perinatal factors evaluated on the association of the
candidate genes with the phenotypes were detected. CONCLUSIONS: Our observation
suggests that AGT-rs699 and FTO-rs17817449 variants may contribute to the risk
development of excess weight and an increase in the BMI, while IRS2-rs1805097
showed a protector effect; in addition, UCP3- rs1800849 showed a decreasing waist
circumference. Socioeconomic and perinatal factors had no effect on the
associations of the candidate gene.
PMID- 28690686
TI - Vagus nerve stimulation as a potential adjuvant to behavioral therapy for autism
and other neurodevelopmental disorders.
AB - BACKGROUND: Many children with autism and other neurodevelopmental disorders
undergo expensive, time-consuming behavioral interventions that often yield only
modest improvements. The development of adjunctive interventions that can
increase the benefit of rehabilitation therapies is essential in order to improve
the lives of individuals with neurodevelopmental disorders. MAIN TEXT: Vagus
nerve stimulation (VNS) is an FDA approved therapy that is safe and effective in
reducing seizure frequency and duration in individuals with epilepsy. Individuals
with neurodevelopmental disorders often exhibit decreased vagal tone, and studies
indicate that VNS can be used to overcome an insufficient vagal response.
Multiple studies have also documented significant improvements in quality of life
after VNS therapy in individuals with neurodevelopmental disorders. Moreover,
recent findings indicate that VNS significantly enhances the benefits of
rehabilitative training in animal models and patients, leading to greater
recovery in a variety of neurological diseases. Here, we review these findings
and provide a discussion of how VNS paired with rehabilitation may yield benefits
in the context of neurodevelopmental disorders. CONCLUSIONS: VNS paired with
behavioral therapy may represent a potential new approach to enhance
rehabilitation that could significantly improve the outcomes of individuals with
neurodevelopmental disorders.
PMID- 28690687
TI - The role of nonverbal working memory in morphosyntactic processing by children
with specific language impairment and autism spectrum disorders.
AB - BACKGROUND: Both children with autism spectrum disorders (ASD) and children with
specific language impairment (SLI) have been shown to have difficulties with
grammatical processing. A comparison of these two populations with
neurodevelopmental disorders was undertaken to examine similarities and
differences in the mechanisms that may underlie grammatical processing. Research
has shown that working memory (WM) is recruited during grammatical processing.
The goal of this study was to examine morphosyntactic processing on a grammatical
judgment task in children who varied in clinical diagnosis and language abilities
and to assess the extent to which performance is predicted by nonverbal working
memory (WM). Two theoretical perspectives were evaluated relative to performance
on the grammatical judgment task-the "working memory" account and the "wrap-up"
account. These accounts make contrasting predictions about the detection of
grammatical errors occurring early versus late in the sentence. METHODS:
Participants were 84 school-age children with SLI (n = 21), ASD (n = 27), and
typical development (TD, n = 36). Performance was analyzed based on diagnostic
group as well as language status (normal language, NL, n = 54, and language
impairment, LI, n = 30). A grammatical judgment task was used in which the
position of the error in the sentence (early versus late) was manipulated. A
visual WM task (N-back) was administered and the ability of WM to predict
morphosyntactic processing was assessed. RESULTS: Groups differed significantly
in their sensitivity to grammatical errors (TD > SLI and NL > LI) but did not
differ in nonverbal WM. Overall, children in all groups were more sensitive and
quicker at detecting errors occurring late in the sentence than early in the
sentence. Nonverbal WM predicted morphosyntactic processing across groups, but
the specific profile of association between WM and early versus late error
detection was reversed for children with and without language impairment.
CONCLUSIONS: Findings primarily support a "wrap up" account whereby the
accumulating sentence context for errors positioned late in the sentence (rather
than early) appeared to facilitate morphosyntactic processing. Although none of
the groups displayed deficits in visual WM, individual differences in these
nonverbal WM resources predicted proficiency in morphosyntactic processing.
PMID- 28690688
TI - Cross-cultural adaptation and validation to Brazil of the scale of attitudes
toward physician-pharmacists collaboration.
AB - BACKGROUND: Despite the increasing complexity of medication therapies and the
expansion of pharmaceutical clinical services to optimize patient care working in
collaboration with physicians. In this sense, interdisciplinary education has
been encouraged. However, no instrument is available to measure attitudes toward
collaborative relationships. OBJECTIVE: To translate, cross-cultural adaptation
and validation an instrument to measure collaboration attitudes toward students
of medicine/pharmacy and physicians/pharmacists. METHODS: The process of cross
cultural adaptation was carried out using international recommendations and was
performed from January 2014 to April 2015. The instrument under consideration was
translated and re-translated. A panel of experts compared the generated documents
and the translation was evaluated for 20 undergraduate students of Pharmacy, 20
undergraduate students of Medicine and professionals (20 pharmacists and 20
physicians). RESULTS: The process of cross-cultural translation and validation
result in the Portuguese version. Modifications to the grammatical structures
were made in order to establish a cross-cultural similarity between the English
and Portuguese versions. Regarding the evaluation of the expert panel, six
questions required modifications. CONCLUSIONS: Psychometric evaluation
demonstrated and confirmed the validity of the Brazilian-Portuguese version to
assess collaborative attitudes among pharmacists and physicians. Moreover, the
scale can be used to evaluate undergraduates and postgraduates and foster the
development of teaching methods that promote comprehensive attitudes in patient
care.
PMID- 28690689
TI - Vancomycin use, dosing and serum trough concentrations in the pediatric
population: a retrospective institutional review.
AB - BACKGROUND: Vancomycin is used primarily for Gram-positive infections.
Recommended dosage regimens and targeted therapeutic levels vary between
institutions. OBJECTIVES: This study aims to describe therapeutic levels
according to initial vancomycin doses and patient's age. A secondary objective
was to evaluate appropriateness of vancomycin use in our hospital. METHODS: A
retrospective chart review was conducted at the Children's Hospital of Eastern
Ontario. Patients included in this study were classified by age (neonates,
infants, children and adolescents) and categorized into those who received
vancomycin <=5 and >5 days. Initial vancomycin dosing regimens and corresponding
initial trough levels obtained were evaluated. Initial trough levels drawn in
relation to the third, fourth, or fifth doses corresponding to the first course
of therapy were analyzed. Acceptable trough levels ranged from 5-20 mg/L.
RESULTS: One-hundred-and-sixty-four patients who received intravenous vancomycin
in 2013 were included. Of the 229 courses of vancomycin, 190 (83%) were used 5
days or less (mean 4.9 days). Sixteen infants (88.9%) and 21 adolescents (100%),
who received vancomycin empiric dosing of 60 mg/kg/day, had initial trough levels
>5mg/L. However, in the children's group 20 (37.7%) did not reach levels >5 mg/L.
None of vancomycin minimum inhibitory concentration (MIC) values were >1mg/L for
the four patients who had infections due to methicillin-resistant Staphylococcus
aureus strains. CONCLUSIONS: In our institution, initial empiric vancomycin
dosing of 60 mg/kg/day resulted in levels >=5mg/L in most infants and
adolescents. It remains unclear why some children aged 1-12 years did not achieve
these levels.
PMID- 28690690
TI - Community pharmacy in Lebanon: A societal perspective.
AB - OBJECTIVE: To assess patients' attitudes towards the community pharmacist's role
and determine their negative and positive reactions towards community pharmacists
in Lebanon. METHODS: A cross-sectional study, conducted between January and April
2016, was designed to assess the general public satisfaction with the services
provided by the community pharmacies. It was carried out, using a proportionate
random sampling of Lebanese community pharmacies from each district. Two sided
statistical tests were used to compare between group percentages, Wilcoxon test
for quantitative variables with non-homogeneous variances or non-normal
distribution, and Student's t-test for quantitative variables of normal
distribution and homogeneous variances. The ANOVA test was used to compare
between three groups or more, and Pearson correlation coefficient were used to
correlate between quantitative variables. RESULTS: a total of 565 participants
completely answered the survey questions with a response rate of 94%. The
bivariate analysis showed that the patient perception index was positively and
significantly correlated with the patient level of expectation index, the overall
pharmacy experience and the patient's reason for visiting the pharmacy (p<0.001
for all 3 variables) but was negatively correlated with the barriers for asking
questions significantly (p=0.032). On the other hand, this perception index was
significantly and positively associated with the number of pharmacy visits, the
age categories, the level of education and the family monthly income (p<0.05 for
all variables). CONCLUSION: Public perception and attitude toward community
pharmacist in Lebanon is poor despite highly qualified pharmacists. Aspects of
pharmacy services most relevant to patients were respect, empathy, a friendly
staff, listening carefully, giving quality time, responding quickly to their
needs and respecting their privacy. The ministry of Health in Lebanon, along with
the Lebanese Order of Pharmacists should educate the pharmacist about working on
the different issues patients are complaining about in order to play a more
important role in the society and become the number one trusted health care
professional.
PMID- 28690691
TI - Impact of a pharmacy technician-centered medication reconciliation program on
medication discrepancies and implementation of recommendations.
AB - OBJECTIVES: To evaluate the impact of a pharmacy-technician centered medication
reconciliation (PTMR) program by identifying and quantifying medication
discrepancies and outcomes of pharmacist medication reconciliation
recommendations. METHODS: A retrospective chart review was performed on two
hundred patients admitted to the internal medicine teaching services at Cooper
University Hospital in Camden, NJ. Patients were selected using a stratified
systematic sample approach and were included if they received a pharmacy
technician medication history and a pharmacist medication reconciliation at any
point during their hospital admission. Pharmacist identified medication
discrepancies were analyzed using descriptive statistics, bivariate analyses.
Potential risk factors were identified using multivariate analyses, such as
logistic regression and CART. The priority level of significance was set at 0.05.
RESULTS: Three-hundred and sixty-five medication discrepancies were identified
out of the 200 included patients. The four most common discrepancies were
omission (64.7%), non-formulary omission (16.2%), dose discrepancy (10.1%), and
frequency discrepancy (4.1%). Twenty-two percent of pharmacist recommendations
were implemented by the prescriber within 72 hours. CONCLUSION: A PTMR program
with dedicated pharmacy technicians and pharmacists identifies many medication
discrepancies at admission and provides opportunities for pharmacist
reconciliation recommendations.
PMID- 28690692
TI - Provider and patient perception of psychiatry patient health literacy.
AB - BACKGROUND: Inadequate health literacy in adults is a nationwide issue that is
associated with worse health outcomes. There is a paucity of literacy regarding
rates of inadequate health literacy in psychiatric populations. OBJECTIVE: The
aim of the study was to identify an existing tool that would easily identify
patients who had inadequate health literacy, so that a targeted intervention
could be performed. Secondarily we attempted to compare rates of inadequate
health literacy with providers' perception of patients' health literacy. METHODS:
We assessed health literacy in a psychiatric population by administering the
Brief Health Literacy Survey (BHLS). Additionally, all psychiatry residents,
psychiatrists, nurse practitioners, pharmacists, and social workers were surveyed
to assess their perception of patient health literacy. Differences between
patient health literacy and provider expectations of patient health literacy were
compared. RESULTS: Inadequate health literacy was identified in 31 out of 61
patients (50.8%) using 2 questions from the BHLS. Only 9 (29%) of patients who
were identified as having inadequate health literacy were identified by both BHLS
questions. In contrast, almost 100% of providers identified their patients, in
general, as having inadequate health literacy. CONCLUSIONS: These results
identify a higher rate of health literacy in a psychiatric inpatient population
than in the general population. However, providers at this institution likely
over-identify health literacy. This highlights the need for a health literacy
tool that can easily target patients with inadequate health literacy for an
intervention.
PMID- 28690693
TI - A community pharmacy-based cardiovascular risk screening service implemented in
Iran.
AB - BACKGROUND: Cardiovascular disease is a major health concern around the world.
OBJECTIVE: To assess the outcomes and feasibility of a pharmacy-based
cardiovascular screening in an urban referral community pharmacy in Iran.
METHODS: A cross sectional study was conducted in a referral community pharmacy.
Subjects aged between 30-75 years without previous diagnose of cardiovascular
disease or diabetes were screened. Measurement of all major cardiovascular risk
factors, exercise habits, medical conditions, medications, and family history
were investigated. Framingham risk score was calculated and high risk individuals
were given a clinical summary sheet signed by a clinical pharmacist and were
encouraged to follow up with their physician. Subjects were contacted one month
after the recruitment period and their adherence to the follow up recommendation
was recorded. RESULTS: Data from 287 participants were analyzed and 146 were
referred due to at least one abnormal laboratory test. The results showed 26
patients with cardiovascular disease risk greater than 20%, 32 high systolic
blood pressure, 22 high diastolic blood pressures, 50 high total cholesterol
levels, 108 low HDL-C levels, and 22 abnormal blood glucose levels. Approximately
half of the individuals who received a follow up recommendation had made an
appointment with their physician. Overall, 15.9% of the individuals received
medications and 15.9% received appropriate advice for risk factor modification.
Moreover, 7.5% were under evaluation by a physician. CONCLUSION: A screening
program in a community pharmacy has the potential to identify patients with
elevated cardiovascular risk factor. A plan for increased patient adherence to
follow up recommendations is required.
PMID- 28690694
TI - Impact of co-investigators on pharmacy resident research publication.
AB - OBJECTIVE: To explore influences of co-investigators on the successful
publication of a pharmacy residency project. METHODS: We analyzed published and
non-published research presented at a regional pharmacy conference. Abstracts
were matched 1:1 based on state and abstract year. We assessed university
affiliation, number, degree, and H-Index of co-investigators on the abstract.
Descriptive and inferential analyses were used to identify variables associated
with resident publication. RESULTS: University-affiliated programs (p=0.015),
highest H-Index of a non-physician co-investigator (p=0.002), and positive H
Index (>=1) of a non-physician co-investigator (p=0.017) were significant
predictors of resident publication on univariate analyses. There were no
differences in the number of co-investigators (p=0.051), projects with physician
co-investigators (p=1.000), or projects with Doctor of Philosophy (PhD) or Master
of Science (MS) co-investigators (p=0.536) between published and non-published
projects. Multivariate analysis found that the highest H-index of non-physician
co-investigator remained significant as a predictor to resident publication (odds
ratio (OR) 1.09, 95% Confidence Interval (CI) 1.01-1.17). CONCLUSIONS: The
quality of co-investigators, as measured by an increasing H-Index, is associated
with the successful publication of residency projects. More emphasis may need to
be placed on resident research co-investigator selection and training to prepare
pharmacy residents for research and scholarly activity.
PMID- 28690695
TI - Assessment of attitudes and practices of young Malaysian adults about antibiotics
use: a cross-sectional study.
AB - OBJECTIVE: The present study was aimed to evaluate the practices and attitudes of
young Malaysian adults towards the use of antibiotics, and to determine the
socioeconomic factors associated with the antibiotic use. METHODS: A survey was
carried in Cheras community by approaching a conveniently selected sample of 480
participants. A pre-tested questionnaire was used for data collection. RESULT: Of
480 participants approached, 400 agreed to participate in this study, giving a
response rate of 83.3%. The study results showed that 42.75% of the participants
exhibited poor attitudes towards antibiotic usage. Chinese race and high income
were significantly associated with the positive attitudes towards antibiotic
usage. It is shown that the practice of the participants towards antibiotics was
relatively poor. The majority of participants agreed that they do not consult a
doctor for minor illnesses (64%). The main reason for not consulting a doctor was
the high fees of consultation (34.25%) and the inconvenience of visit (29.25%).
However, a large proportion of respondents (77.5%) agreed that there is a need to
enhance antibiotic education among public. CONCLUSION: The study results
identified some crucial gaps in the attitudes and practices of Cheras community
about the use of antibiotics. Thus, improving the public knowledge and changing
their attitude towards antibiotic use along with proper interventions to regulate
the ease of their availability would play a significant role for the effective
use of antibiotics in the community.
PMID- 28690696
TI - Nurses' attitudes and behaviors on patient medication education.
AB - BACKGROUND: Medication education is vital for positive patient outcomes. However,
there is limited information about optimal medication education by nurses during
hospitalization and care transitions. OBJECTIVE: Examine nurses' attitudes and
behaviors regarding the provision of patient medication education. The secondary
objectives were to determine if nurses' medication education attitudes explain
their behaviors, describe nurses' confidence in patient medication knowledge and
abilities, and identify challenges to and improvements for medication education.
METHODS: A cross sectional survey was administered to nurses servicing internal
medicine, cardiology, or medical-surgical patients. RESULTS: Twenty-four nurses
completed the survey. Greater than 90% of nurses believed it is important to
provide information on new medications and medical conditions, utilize resources,
assess patient understanding and adherence, and use open ended question. Only 58%
believed it is important to provide information on refill medications. Greater
than 80% of nurses consistently provided information on new medications, assessed
patient understanding, and utilized resources, but one-third or less used open
ended questions or provided information on refill medications. Most nurses spend
5-9 minutes per patient on medication education and their attitudes matched the
following medication education behaviors: assessing adherence (0.57; p<0.01),
providing information on new medications (0.52; p<0.05), using open-ended
questions (0.51; p<0.01), and providing information on refill medications (0.39;
p<0.05). Nurses had higher confidence that patients can understand and follow
medication instructions, and identify names and purpose of their medications.
Nurses had lower confidence that patients know what to expect from their
medication or how to manage potential side effects. Communication, including
language barriers and difficulty determining the patient's understanding of the
information, was the most common challenge for nurses and they suggested
utilization of translator services and patient-friendly drug information
resources as a way to improve. CONCLUSION: Nurses have positive attitudes toward
patient medication education. However, their attitudes do not fully explain their
behaviors and many nurses are spending limited time with patients on medication
education. Enhancements to medication education could include resources on
communication and collaboration with pharmacists.
PMID- 28690697
TI - Challenges in the management of community pharmacies in Malaysia.
AB - BACKGROUND: The provision of professional pharmacy services by community
pharmacists continues to be limited, particularly in low and middle income
countries. It was postulated that multiple management challenges faced by
community pharmacists contribute to this situation. OBJECTIVE: The primary aim of
the research was to determine the challenges faced in the management of community
pharmacies in Sarawak (the largest state in Malaysia), and practical strategies
to cope and overcome the challenges. METHODS: Semi-structured interviews were
carried out with community pharmacists practising in Sarawak. Purposive and
snowball sampling were employed to ensure a diverse group of informants. The
interviews were audio-recorded and transcribed verbatim, with the resultant data
analysed using thematic analysis. Data collection, coding, interpretation were
carried out iteratively until theoretical saturation. RESULTS: Twenty respondents
from different demographic characteristics were recruited. Six major themes were
identified. Management challenges faced by community pharmacists traverse five
major domains: market competition, legislative issues, customers' knowledge and
expectations, macroeconomic impacts and operational challenges. Most of these
challenges require government intervention to be resolved. In the meantime,
improving customer service and expanding the range of professional services were
seen as the most viable strategies to cope with existing challenges. The main
concern is that current legislative and economic landscape may hinder these
strategies. Enactment of dispensing separation and more protective measures
against market competition were suggested to alleviate the challenges faced.
CONCLUSION: Numerous management challenges faced by community pharmacists that
distract them from delivering professional pharmacy services have been
highlighted. Urgent affirmative actions by the government are warranted in
supporting community pharmacists to realise and maximise their potentials.
PMID- 28690698
TI - Assessment of the rates and characteristics of the short-term supply of
medication (Tider) from an integrated healthcare delivery system in the United
States.
AB - OBJECTIVES: The purpose of this study was to describe the rate of medication
short-term supply dispensings (tider), patient and medication characteristics
associated with a tider, and costs for tider dispensings in an integrated
healthcare delivery system in Colorado, United States. METHODS: This was a
retrospective study conducted in an integrated healthcare delivery system's
outpatient clinics. All patients who had a prescription dispensed for a study
medication at any of the system's 28 outpatient pharmacies during the first
quarter of 2016 were included. A tider was identified as a 3-day supply of a
prescription medication that was dispensed at no charge to a patient. The
quarterly tider rate and the per member per month (PMPM) cost of tiders were
estimated. Patient and medication characteristics associated with a tider were
assessed. RESULTS: A total of 444,225 study medications were dispensed for
135,907 patients during the study period. There were 3,430 (0.77%, 95%CI
0.75%:0.80%) medications dispensed as a tider. The PMPM cost of tider medications
and their dispensing fees was USD 0.03. There were 1,092 (0.8%) and 134,815
(99.2%) patients who did and did not, respectively, have at least one tider
dispensed during the study period. Patient characteristics strongly associated
with having had a tider dispensed included being older, male, and a Medicare
beneficiary. Cardiovascular and neuromuscular medications had the highest rates
of tider dispensing. CONCLUSIONS: The rate of tider dispensing was relatively
low; however, approximately one out of 125 patients had at least one tider.
Patients who had a tider were more likely to be older, female, a Medicare
beneficiary, and having had a previous tider dispensing and a higher burden of
chronic disease. The tider medication was more likely to be a cardiovascular or
neuromuscular medication class and more likely to be dispensed on a weekend. The
total cost of dispensing a tider appears reasonable since the benefits of
providing patients with needed medications likely outweigh the cost. Future
studies should be performed to assess the impact of tider dispensing on health
outcomes.
PMID- 28690699
TI - Feasibility of clinical pharmacist-led CYP2C19 genotyping for patients receiving
non-emergent cardiac catheterization in an integrated health system.
AB - OBJECTIVE: To assess the feasibility of clinical pharmacist-led CYP2C19 genotype
guided P2Y12 inhibitor antiplatelet drug therapy recommendations to cardiologists
in an outpatient cardiology practice. METHODS: This was a prospective, open
labeled, single-arm study conducted in an integrated healthcare delivery system
between March 1, 2013 and January 23, 2014. Patients requiring non-emergent
cardiac catheterization were included. A clinical pharmacist provided
interpretation and recommendations from genotyping results. The feasibility of
implementing CYP2C19 genotype-guided antiplatelet therapy was assessed by the: 1)
percentage of patients approached who consented to CYP2C19 genotyping, 2)
percentage of patients with CYP2C19 genotyping results available prior to cardiac
catheterization, and 3) percentage of clinical pharmacist CYP2C19 genotype-based
antiplatelet recommendations accepted by cardiologists. RESULTS: Of the 43
patients identified for potential recruitment, 22 of these were eligible for
study enrollment and 6 (27%) patients consented and received CYP2C19 genotyping.
All patients had genotyping results available prior to catheterization and all
clinical pharmacists' antiplatelet therapy recommendations were accepted by the
patients' cardiologists. Three patients had the CYP2C19 wild-type (*1/*1)
genotype and the clinical pharmacist recommended clopidogrel therapy. CYP2C19
variant genotypes (i.e., *1/*2, *1/*17, and *2/*17) were found in the other three
patients; alternative antiplatelet therapy was recommended for the patient with
the *1/*2 genotype, while clopidogrel was recommended for those with *1/*17 and
*2/*17 genotypes. CONCLUSION: A relatively small proportion of patients
undergoing non-emergent cardiac catheterization consented to pharmacogenetic
testing; however, their cardiologists were receptive to clinical pharmacists
conducting such testing and providing corresponding pharmacotherapy
recommendations. Future studies should identify patient barriers to
pharmacogenetic testing.
PMID- 28690700
TI - Effects of staff education and standardizing dosing and collection times on
vancomycin trough appropriateness in ward patients.
AB - BACKGROUND: Many institutions have guidelines for initiation and monitoring, but
not timing, of vancomycin. OBJECTIVE: Our objective was to evaluate vancomycin
trough collection appropriateness before and after an initiative to change the
dosing and trough collection times in ward patients. METHODS: A retrospective
cohort study of ward patients from May 2014-16 who received scheduled intravenous
vancomycin was performed. Nurse managers and pharmacists provided staff
education. Differences between pre- and post-intervention groups were compared
using student's t-test for continuous data and chi-square test for categorical
data. RESULTS: Baseline characteristics were similar between the pre-intervention
(n=124) and post-intervention (n=122) groups except for weight-based maintenance
dose (15.3 mg/kg vs. 16.5 mg/kg, p=0.03) and percentage of troughs collected with
morning labs (14% vs. 87%, p<0.001). Patients in the pre- and post-intervention
groups received a similar frequency of loading doses (14.5% vs. 16%, p=0.68).
There was no significant difference in percentage of vancomycin troughs collected
appropriately at 30 (40% vs. 42%, p=0.72), 60 (57% vs. 63%, p=0.35), or 75 (60%
vs. 68%, p=0.22) minutes from the scheduled time of the next dose. CONCLUSION:
Staff education and standardizing collection of vancomycin troughs with morning
blood collections did not affect the percentage of appropriately collected
vancomycin troughs.
PMID- 28690701
TI - Models and theories of prescribing decisions: A review and suggested a new model.
AB - To date, research on the prescribing decisions of physician lacks sound
theoretical foundations. In fact, drug prescribing by doctors is a complex
phenomenon influenced by various factors. Most of the existing studies in the
area of drug prescription explain the process of decision-making by physicians
via the exploratory approach rather than theoretical. Therefore, this review is
an attempt to suggest a value conceptual model that explains the theoretical
linkages existing between marketing efforts, patient and pharmacist and physician
decision to prescribe the drugs. The paper follows an inclusive review approach
and applies the previous theoretical models of prescribing behaviour to identify
the relational factors. More specifically, the report identifies and uses several
valuable perspectives such as the 'persuasion theory - elaboration likelihood
model', the stimuli-response marketing model', the 'agency theory', the theory of
planned behaviour,' and 'social power theory,' in developing an innovative
conceptual paradigm. Based on the combination of existing methods and previous
models, this paper suggests a new conceptual model of the physician decision
making process. This unique model has the potential for use in further research.
PMID- 28690702
TI - Journal Aspirations: Improving Scientific Writing and Publication Through a
Writing Mentorship Program.
AB - Looking to help novice scientific writers improve their skills and enhance the
likelihood of scientific publication, the IJTMB launched a writing mentorship
program. Research indicates that when novice writers have a mentor and work on
writing as a team, the authors can gain self-efficacy, manuscripts are improved,
thoughts and writing are clarified, and differing perspectives are added. This
editorial identifies the process for being recommended to use a writing mentor,
discusses recommendations in the forming of a mentor/mentee relationship,
describes the qualities of good mentors and mentees, and offers suggestions for
improving writing for scientific publication. As our database of writing mentors
grows, we encourage those who join this program both as mentors and as mentees to
consider what it means to be in these roles. It is my hope that the suggestions
herein help in developing these relationships.
PMID- 28690703
TI - The Effectiveness of Thai Massage and Joint Mobilization.
AB - BACKGROUND: Non-specific low back pain (LBP) is a common health problem resulting
from many risk factors and human behaviors. Some of these may interact
synergistically and have been implicated in the cause of low back pain. Massage
both traditional Thai massage and joint mobilization as a common practice has
been shown to be effective for some subgroup of nonspecific LBP patients. PURPOSE
AND SETTING: The trial compared the effectiveness between traditional Thai
massage and joint mobilization for treating nonspecific LBP. Some associated
factors were included. The study was conducted at the orthopedic outpatient
department, Lerdsin General Hospital, Bangkok, Thailand. METHODS: Prospective,
randomized study was developed without control group. The required sample size
was estimated based on previous comparative studies for effectiveness between
techniques. Two primary outcome measures were a 0 to 10 visual analog scale (VAS)
of pain and Oswestry Disability Index (ODI). Secondary outcome measures were
satisfaction of patients and adverse effects of the treatment. The "intention to
treat" (ITT) and per protocol approach were used to compare the significance of
the difference between treatment groups. PARTICIPANTS: One hundred and twenty
hospital outpatients, 20 (16.7%) male and 100 (83.3%) female, were randomized
into traditional Thai massage and joint mobilization therapy. The average age of
traditional Thai massage and joint mobilization was 50.7 years and 48.3 years,
respectively. Both groups received each treatment for approximately 30 minutes
twice per week over a four-week period. Total course did not exceed eight
sessions. RESULT: With ITT, the mean VAS of traditional Thai massage group before
treatment was 5.3 (SD = 1.7) and ODI was 24.9 (SD = 14.7), while in joint
mobilization groups, the mean VAS was 5.0 (SD = 1.6) and ODI was 24.6 (SD = 15).
After treatment, the mean VAS and ODI were significantly reduced (VAS = 0.51 (SD
= 0.89) and ODI = 8.1 (SD = 10.7) for traditional Thai massage, VAS = 0.86 (SD =
1.49) and ODI = 8.26 (SD = 12.97) for joint mobilization). Constipation was found
in 34 patients (28.3%). CONCLUSION: The traditional Thai massage and joint
mobilization used in this study were equally effective for short-term reduction
of pain and disability in patients with chronic nonspecific LBP. Both techniques
were safe with short term effect in a chosen group of patients.
PMID- 28690704
TI - Experienced Practitioners' Beliefs Utilized to Create a Successful Massage
Therapist Conceptual Model: a Qualitative Investigation.
AB - BACKGROUND: The massage therapy profession in the United States has grown
exponentially, with 35% of the profession's practitioners in practice for three
years or less. Investigating personal and social factors with regard to the
massage therapy profession could help to identify constructs needed to be
successful in the field. PURPOSE: This data-gathering exercise explores massage
therapists' perceptions on what makes a successful massage therapist that will
provide guidance for future research. Success is defined as supporting oneself
and practice solely through massage therapy and related, revenue-generating field
activity. PARTICIPANTS AND SETTING: Ten successful massage therapy practitioners
from around the United States who have a minimum of five years of experience.
RESEARCH DESIGN: Semistructured qualitative interviews were used in an analytic
induction framework; index cards with preidentified concepts printed on them were
utilized to enhance conversation. An iterative process of interview coding and
analysis was used to determine themes and subthemes. RESULTS: Based on the
participants input, the categories in which therapists needed to be successful
were organized into four main themes: effectively establish therapeutic
relationships, develop massage therapy business acumen, seek valuable learning
environments and opportunities, and cultivate strong social ties and networks.
The four themes operate within specific contexts (e.g., regulation and licensing
requirements in the therapists' state), which may also influence the success of
the massage therapist. CONCLUSIONS: The model needs to be tested to explore which
constructs explain variability in success and attrition rate. Limitations and
future research implications are discussed.
PMID- 28690705
TI - Community Care for Older Adults-the Patient/Caregiver Perspective.
PMID- 28690706
TI - Planning Health Services for Seniors: Can We Use Patient's Own Perception?
AB - OBJECTIVES: The objectives of this study were to identify needs and to estimate
whether self-reported health can be used as an indicator of service needs among
seniors. METHODS: This was a cross-sectional survey. Age- and sex-adjusted
logistic regression was used to estimate the link between functional status
indicators and fair or poor self-reported health. Forward stepwise logistic
regression was performed to identify the strongest contributors of poor health.
Positive predictive value (PPV), sensitivity, and specificity were calculated to
identify whether health perception could be used to identify people in need of
physical rehabilitation services. RESULTS: 142 seniors agreed to answer the
survey, yielding a response rate of 73%. Among the respondents (mean age 79+/-7;
60% women), 40% rated their health as fair or poor. Seniors perceiving their
health as fair or poor had higher odds of reporting impairments, activity
limitations, and participation restrictions (OR ranging from 2.37 95%CI: 1.03-5
45 to 12.22 95%CI: 2.68-55.78) in comparison to those perceiving their health as
good or better. The strongest contributors for poor/fair health were depression,
difficulty performing household tasks, pain, and dizziness (c-statistic = 0.91
and a maximum adjusted r-squared of 0.60). Self-rated health used as single-item
showed a positive predictive value (PPV) of 1, sensitivity of 52%, and
specificity of 100%. CONCLUSION: Our results indicate that all seniors
participating in this study and reporting fair or poor health have indicators of
need for further rehabilitation services. Asking patients to rate their own
health may be an alternate way of querying about need, as many older persons are
afraid to report disability because of fear of further institutionalization.
PMID- 28690707
TI - Understanding How to Support Family Caregivers of Seniors with Complex Needs.
AB - PURPOSE OF THE STUDY: The purpose of this study was to describe the experiences
and challenges of supporting family caregivers of seniors with complex needs and
to outline support strategies and research priorities aimed at supporting them.
DESIGN AND METHODS: A CIHR-funded, two-day conference entitled "Supporting Family
Caregivers of Seniors: Improving Care and Caregiver Outcomes" was held. An
integrated knowledge translation approach guided this planning conference. Day 1
included presentations of research evidence, followed by participant engagement
Qualitative data was collected regarding facilitators, barriers/gaps, and
recommendations for the provision of caregiver supports. Day 2 focused on
determination of research priorities. RESULTS: Identified facilitators to the
provision of caregiver support included accessibility of health-care and
community-based resources, availability of well-intended health-care providers,
and recognition of caregivers by the system. Barriers/gaps related to challenges
with communication, access to information, knowledge of what is needed, system
navigation, access to financial resources, and current policies. Recommendations
regarding caregiver services and research revolved around assisting caregivers to
self-identify and seek support, formalizing caregiver supports, centralizing
resources, making system navigation available, and preparing the next generation
for caregiving. IMPLICATION: A better understanding of the needs of family
caregivers and ways to support them is critical to seniors' health services
redesign.
PMID- 28690708
TI - Caring in the Information Age: Personal Online Networks to Improve Caregiver
Support.
AB - BACKGROUND: It is becoming increasingly important to find ways for caregivers and
service providers to collaborate. This study explored the potential for improving
care and social support through shared online network use by family caregivers
and service providers in home care. METHODS: This qualitative study was guided by
Rogers' Theory of Diffusion of Innovations [NY: Free Press; 1995], and involved
focus group and individual interviews of service providers (n = 31) and family
caregivers (n = 4). Interview transcriptions were analyzed using descriptive,
topic, and analytic coding, followed by thematic analysis. RESULTS: The network
was identified as presenting an opportunity to fill communication gaps presented
by other modes of communication and further enhance engagement with families.
Barriers included time limitations and policy-related restrictions, privacy,
security, and information ownership. CONCLUSION: Online networks may help address
longstanding home-care issues around communication and information-sharing. The
success of online networks in home care requires support from care partners.
Future research should pilot the use of online networks in home care using
barrier and facilitator considerations from this study.
PMID- 28690709
TI - Polymyalgia Rheumatica in Association with Remitting Seronegative Sinovitis with
Pitting Edema: a Neoplastic Warning.
PMID- 28690710
TI - The Role of Simulation in the Design of a Semi-Enclosed Tubular Embolus
Retrieval.
AB - A numerical analysis of a semi-enclosed tubular mechanical embolus retrieval
device (MERD) for the treatment of acute ischemic stroke (AIS) is presented. In
this research, the finite element analysis (FEA) methodology is used to evaluate
mechanical performance and provide suggestions for optimizing the geometric
design. A MERD fabricated from nickel-titanium alloy (Nitinol) tubing is
simulated and analyzed under complex in vivo loading conditions involving shape
setting, crimping, deployment, and embolus retrieval. As a result, the peak
strain of the shape-setting procedure is proved to be safe for the device
pattern. However, the MERD shows poor mechanical behavior after crimping into a
catheter, because the peak crimping strain obtains a value of 12.1%. The delivery
and deployment step demonstrates that the artery wall has little risk of serious
injuries or rupture. In addition, the process of simulation of embolus retrieval
and device system migration inside the cerebral artery lumen provides useful
information during the design process.
PMID- 28690711
TI - Design of a Magnetic Resonance Imaging Guided Magnetically Actuated Steerable
Catheter.
AB - This paper presents design optimization of a magnetic resonance imaging (MRI)
actuated steerable catheter for atrial fibrillation ablation in the left atrium.
The catheter prototype, built over polymer tubing, is embedded with current
carrying electromagnetic coils. The prototype can be deflected to a desired
location by controlling the currents passing through the coils. The design
objective is to develop a prototype that can successfully accomplish the ablation
task. To complete the tasks, the catheter needs to be capable of reaching a set
of desired targets selected by a physician on the chamber and keeping a stable
contact with the chamber surface. The design process is based on the maximization
of the steering performance of the catheter by evaluating its workspace in free
space. The selected design is validated by performing a simulation of an ablation
intervention on a virtual model of the left atrium with a real atrium geometry.
This validation shows that the prototype can reach every target required by the
ablation intervention and provide an appropriate contact force against the
chamber.
PMID- 28690712
TI - Finite Element Analysis of the Implantation Process of Overlapping Stents.
AB - Overlapping stents are widely used in vascular stent surgeries. However, the rate
of stent fractures (SF) and in-stent restenosis (ISR) after using overlapping
stents is higher than that of single stent implantations. Published studies
investigating the nature of overlapping stents rely primarily on medical images,
which can only reveal the effect of the surgery without providing insights into
how stent overlap influences the implantation process. In this paper, a finite
element analysis of the overlapping stent implantation process was performed to
study the interaction between overlapping stents. Four different cases, based on
three typical stent overlap modes and two classical balloons, were investigated.
The results showed that overlapping contact patterns among struts were edge-to
edge, edge-to-surface, and noncontact. These were mainly induced by the
nonuniform deformation of the stent in the radial direction and stent tubular
structures. Meanwhile, the results also revealed that the contact pressure was
concentrated in the edge of overlapping struts. During the stent overlap process,
the contact pattern was primarily edge-to-edge contact at the beginning and edge
to-surface contact as the contact pressure increased. The interactions between
overlapping stents suggest that the failure of overlapping stents frequently
occurs along stent edges, which agrees with the previous experimental research
regarding the safety of overlapping stents. This paper also provides a
fundamental understanding of the mechanical properties of overlapping stents.
PMID- 28690713
TI - Thermodynamics of the Flexible Metal-Organic Framework Material MIL-53(Cr) From
First Principles.
AB - We use first-principles density functional theory total energy and linear
response phonon calculations to compute the Helmholtz and Gibbs free energy as a
function of temperature, pressure, and cell volume in the flexible metal-organic
framework material MIL-53(Cr) within the quasiharmonic approximation. GGA and
metaGGA calculations were performed, each including empirical van der Waals (vdW)
forces under the D2, D3, or D3(BJ) parameterizations. At all temperatures up to
500 K and pressures from -30 MPa to 30 MPa, two minima in the free energy versus
volume are found, corresponding to the narrow pore (np) and large pore (lp)
structures. Critical positive and negative pressures are identified, beyond which
there is only one free energy minimum. While all results overestimated the
stability of the np phase relative to the lp phase, the best overall agreement
with experiment is found for the metaGGA PBEsol+RTPSS+U+J approach with D3 or
D3(BJ) vdW forces. For these parameterizations, the calculated free energy
barrier for the np-lp transition is only 3 to 6 kJ per mole of Cr4(OH)4(C8H4O4)4.
PMID- 28690714
TI - Trauma-Focused Cognitive Behavioral Therapy for Commercially Sexually Exploited
Youth.
AB - Commercially sexually exploited children and adolescents ("commercially exploited
youth")present numerous clinical challenges that have led some mental health
providers to question whether current evidence-based treatments are adequate to
address the needs of this population. This paper 1) addresses commonalities
between the trauma experiences, responses and treatment challenges of
commercially exploited youth and those of youth with complex trauma; 2)
highlights the importance of careful assessment to guide case conceptualization
and treatment planning for commercially exploited youth; and 3) describes
strategies for implementing Trauma-Focused Cognitive Behavioral Therapy for
complex trauma specific to these youth.
PMID- 28690715
TI - A novel aerodynamic sizing method for pharmaceutical aerosols using image-based
analysis of settling velocities.
AB - This article discusses a novel method to estimate aerodynamic particle size
distributions (APSDs) of pharmaceutical aerosols through direct measurement of
particle settling velocities using image-based analysis and particle tracking
techniques. This simple, optical method provides accurate and fast measurements
(approximately 1 minute) with few sources of bias due to specific device design
choices or operation conditions. A proof-of-concept for the method is
demonstrated by measuring APSDs for widely available commercial dry powder
inhalers (DPIs), then comparing the results with previously published data from
cascade impactors (CIs) and the Aerodynamic Particle Sizer (APS).
PMID- 28690716
TI - Wilson's disease and diagnostic conundrum in a low income country.
AB - Wilson's disease is a well-known leading cause of chronic liver disease in
children. However it may remain undiagnosed in a resource limited setting for a
long period. We describe a six year male child diagnosed Wilson's disease with
extreme elevation of liver enzymes which is not reported earlier. The diagnosis
was also baffling because of inconsistency of other laboratory parameters.
PMID- 28690717
TI - [Swelling involving the nasolabial region: nasolabial cyst should be suspected].
PMID- 28690718
TI - [Conjunctival carcinoma in situ: a rare lesion that should not be ignored].
PMID- 28690719
TI - [Inverted papilloma of the bladder: a rare benign tumor: a case report].
PMID- 28690720
TI - [Cerebral hydatid cysts in children: about 15 cases].
PMID- 28690721
TI - [Fenton's naviculo-capitate fracture syndrome (about a case)].
PMID- 28690722
TI - [Confluent and reticulated papillomatosis of Gougerot-Carteaud: about a case].
PMID- 28690723
TI - [Risk factors for maternal and perinatal mortality among women undergoing
cesarean section in Lubumbashi, Democratic Republic of Congo II].
PMID- 28690724
TI - Imaging of complicated frontal sinusitis.
AB - Complications occur in 3% of the cases of frontal sinusitis. These are mainly
oculo-orbital, intracranial and osteomyelitis. Our aim is to describe the
contribution of different imaging modalities in the diagnosis of these
complications and their post-treatment monitoring. within a 15 years period (2000
2014), 10 patients with complicated frontal sinusitis were included into this
retrospective study. 10 patients (9 males) aged 9 to 70 year old (mean 28). Two
of these patients (20%) had a history of craniofacial trauma. Frontal headache
was present in all cases (100%), frontal swelling in 8 cases (80%) and unilateral
palpebral edema in 3 cases (30%). A CT scan of the face and brain was performed
in all cases and revealed frontal osteomyelitis in 6 cases (60%), extradural
empyema in 3 cases (33%), intracranial frontal abscess in 2 cases (20%) and
occulo-orbital complications in 3 cases (30%). Magnetic resonance imaging was
performed in one patient and demonstrated thrombosis of the upper longitudinal
sinus. 40% of our patients associated 2 complications. Cross-sectional imaging is
important in early and accurate diagnosis of complicated frontal sinusitis.
PMID- 28690725
TI - [Lytic lesion involving the first phalanx: sarcoidosis should be suspected].
PMID- 28690726
TI - [Giant parathyroid carcinoma: diagnostic difficulties and therapeutic
strategies].
AB - Parathyroid carcinoma is a very rare malignancy responsible for 0.4 to 5.2% of
hyperparathyroidism. Clinical diagnosis is difficult and treatment should be
codified. Surgery is the only curative treatment. We report the case of a female
patient treated for malignancy-associated hypercalcemia revealing parathyroid
carcinoma. The patient underwent surgery; after three months she developed
lymphatic recurrence. Given the absence of other secondary involvement, bilateral
lymph node dissection followed by chemotherapy was performed. Parathyroid
carcinoma is often suspected on the basis of biological, radiological and
especially intraoperative macroscopic criteria, but definitive diagnosis is made
histopathologically. Surgery is currently the only curative treatment and the
role of adjuvant therapy is to establish.
PMID- 28690727
TI - [Clinical and immunological profile of 15 Moroccan patients with Hyper IgM
syndrome].
AB - Hyper IgM syndrome is a well known genetic (primary) immunodeficiency disorder
which was first described in 1961. It is caused by B lymphocyte deficiency
characterized by normal or elevated serum IgM levels and low or zero levels of
IgG, IgA, IgE resulting from isotype-switching deficiency. Clinical
manifestations are dominated by recurrent infections, especially involving the
digestive tube of the ENT sphere and the lungs. This syndrome is caused by B-cell
immunoglobulin class switch deficiency and decreased capacity to induce
proliferation of T lymphocytes. The net result of these deficiencies is reflected
in increased susceptibility to Pneumocystis jiroveci, Cryptosporidium spp and
other intracellular organisms as well as high rate of bacterial and viral
infections. This study aimed to illustrate the importance of understanding the
pathophysiological mechanisms associated with this increased susceptibility to
infections in order to allow a better diagnosis and therapy in patients with
Hyper IgM syndrome (HIM).
PMID- 28690728
TI - [Drug induced angioedema: a rare side effect of simvastatin].
PMID- 28690729
TI - [Unusual location of multiple hydatidosis, pancreatic and pelvic: about a case].
AB - Hydatid cyst is an infectious disease which is quite frequent in Morocco. Pelvic
and pancreatic locations of this parasitic infection are rare, namely
exceptional. We report the case of a 66-year old patient who was operated for
liver hydatic cyst 6 years before, presenting for chest pain associated with
hydatidoptysis. Chest X-ray objectified left hydropneumothorax. Thoraco
abdominopelvic CT showed mediastinal liquid mass as well as multiple hepatic,
pancreatic (isthmus), pelvic and left under diaphragmatic cystic lesions. Hydatid
serology was positive. Treatment involved thoracotomy associated with medical
treatment.
PMID- 28690730
TI - Septic arthritis of the pubis symphysis: clinical and therapeutic features.
AB - Septic arthritis of the pubis symphysis is rare and difficult to diagnose. The
objective of our study was to describe the biological, clinical, radiological and
therapeutic aspects of this disease. This is a retrospective study of 4 cases of
septic arthritis of the pubic symphysis collected in the Department of
Rheumatology and Orthopaedics in Sousse in Tunisia over a period of 16 years
(2000-2016). Our population consists of 3 women and one men. The mean age was 47
years (18-83). Clinical signs of appeal were inflammatory groin pain, pubic pain
and fever. Symptoms appeared after forceps delivery in 2 cases, after surgery on
the pelvis in one case and in a context of sepsis in one case. Radiographs showed
pubic disjunction with irregular shoreline in all cases. CT performed in all
patients and MRI in 2 patients showed erosions of the banks of the pubic
symphysis with infiltration of the soft parts in all cases. The causative
organisms were isolated in 3 cases by biopsy of soft tissue abscess under CT in 2
cases and vaginal swab in one case. Identified germs were staphylococcus aureus
Meti-S (n=1), proteus mirabilis (n=1) and varied flora (n=1). The treatment
consisted of appropriate antibiotics in all cases and surgical drainage of soft
tissue abscess resistant to medical treatment in 2 cases. The outcome was
favorable in all cases. Diagnosis of septic arthritis of the pubic symphysis is
based on clinic supported by microbiologic culture results, image methods, and
proteins augment during acute phase.
PMID- 28690731
TI - Maternal education and child immunization: the mediating roles of maternal
literacy and socioeconomic status.
AB - INTRODUCTION: Previous studies in Nigeria have documented significant association
between maternal education and child immunization. However, little is known about
the pathway through which maternal education improves immunization uptake. This
study aims to examine whether maternal literacy and socioeconomic status mediates
the relationship between maternal education and complete immunization coverage in
children. METHODS: Nationally representative data from the first wave of the
Nigeria General Household Survey-Panel were used, which includes 661 children
aged one year and below. Regression analyses were used to model the association
between maternal education and child's immunization uptake; we then examined
whether maternal literacy and household economic status mediates this
association. RESULTS: Of the 661 children, 40% had complete immunization. The
prevalence ratio (PR) of complete immunization in children whose mothers were
educated versus those whose mothers were not educated was 1.44 (95% CI: 1.16
1.77). Maternal literacy substantially reduced the estimated association between
maternal education and complete immunization by 90%, whereas household economic
status reduced the estimates by 27%. CONCLUSION: These findings suggest that
complete immunization was higher in children whose mothers were educated, partly
because maternal education leads to acquisition of literacy skills and better
health-seeking behavior which then improves immunization uptake for their
children. Socioeconomic status is an alternative pathway but with less
substantial indirect effect.
PMID- 28690732
TI - Maxillofacial fractures in a budding teaching hospital: a study of pattern of
presentation and care.
AB - INTRODUCTION: Previous reports indicated that there is geographic and
sociodemographic variation in the epidemiology of maxillofacial fractures. Audit
of maxillofacial injuries managed at any institution is therefore necessary to
understand the trends and proffer strategies for prevention. We therefore
embarked on this study to determine the pattern of maxillofacial fractures and
concomitant injuries in our institution. METHODS: We carried out a retrospective
review of information on demography, aetiology and type of maxillofacial
fracture, patients' status, type of crash, level of consciousness and concomitant
injuries. The data collected was analysed with SPSS Version 20. RESULTS: A total
of 233 patients aged 2 to 66 years were reviewed. A higher male preponderance
(M:F 3.4:1) was observed. Road traffic crashes (RTC) accounted for 78.5% of
injuries. Motorcycle related crashes were responsible for 69.4% of RTC and 54.5%
of all fractures. Fracture of the mandible (63.2% n=172) was the most predominant
skeletal injury and the body (25% n=43) was the most common site of fracture
while the zygoma (29%) was predominantly affected in the midface. Ninety three
patients (40%) suffered loss of consciousness. The relationship between aetiology
of injuries and consciousness level of the patients was statistically significant
(p=0.001). Of the 43 patients who had concomitant injuries, craniocerebral
affectation (60.5%) was the commonest. CONCLUSION: RTC remains the major
aetiology of maxillofacial fractures. The mandible was mostly affected and nearly
half of the patients have associated loss of consciousness. There is need for
continual advocacy and enforcement of laws on preventive measures among road
users.
PMID- 28690733
TI - [Rare location of chondromyxoid fibroma: about a case].
PMID- 28690734
TI - Individual and socioeconomic factors associated with childhood immunization
coverage in Nigeria.
AB - INTRODUCTION: Immunization is the world's most successful and cost-effective
public health intervention as it prevents over 2 million deaths annually.
However, over 2 million deaths still occur yearly from Vaccine preventable
diseases, the majority of which occur in sub-Saharan Africa. Nigeria is a major
contributor of global childhood deaths from VPDs. Till date, Nigeria still has
wild polio virus in circulation. The objective of this study was to identify the
individual and socioeconomic factors associated with immunization coverage in
Nigeria through a secondary dataset analysis of Nigeria Demographic and Health
Survey (NDHS), 2013. METHODS: A quantitative analysis of the 2013 NDHS dataset
was performed. Ethical approvals were obtained from Walden University IRB and the
National Health Research Ethics Committee of Nigeria. The dataset was downloaded,
validated for completeness and analyzed using univariate, bivariate and
multivariate statistics. RESULTS: Of 27,571 children aged 0 to 59 months, 22.1%
had full vaccination, and 29% never received any vaccination. Immunization
coverage was significantly associated with childbirth order, delivery place,
child number, and presence or absence of a child health card. Maternal age,
geographical location, education, religion, literacy, wealth index, marital
status, and occupation were significantly associated with immunization coverage.
Paternal education, occupation, and age were also significantly associated with
coverage. Respondent's age, educational attainment and wealth index remained
significantly related to immunization coverage at 95% confidence interval in
multivariate analysis. CONCLUSION: The study highlights child, parental and
socioeconomic barriers to successful immunization programs in Nigeria. These
findings need urgent attention, given the re-emergence of wild poliovirus in
Nigeria. An effective, efficient, sustainable, accessible, and acceptable
immunization program for children should be designed, developed and undertaken in
Nigeria with adequate strategies put in place to implement them.
PMID- 28690735
TI - [Malaria serology test: what contribution does it make in an endemic country such
as Ivory Coast?]
AB - INTRODUCTION: Malaria serology test seems to have attracted very little interest
in endemic countries such as Ivory Coast. However, this examination has been
regularly performed in the parasitology laboratory at the Training and Research
Unit of Medical Sciences in Abidjan. Our study aimed to highlight the
contribution of malaria serology test in our endemic country context. METHODS: We
conducted a retrospective study of malaria serology test using Falciparum-Spot IF
(bioMerieux) kit for the detection of IgG antiplasmodial antibodies. It included
all malaria serology tests performed from January 2007 to February 2011 and whose
results were available in the registry. RESULTS: In total, 136 patients were
selected. The average age of patients was 36,3 years, ranging from 1 to 81 years,
and sex ratio was 0,97. Indications for malaria serology test were varied and
dominated by splenomegaly (49.3%), cytopenias (14.7%), indeterminate fever
(13.2%). Almost all of the patients (98.5%) had antiplasmodial antibodies with
high medium titer of 1057,35IU/ml. There was no link between age and Ab titer,
which was higher in cytopenias, prolonged fevers and the splenomegaly.
CONCLUSION: Malaria serology test seems to have attracted very little interest in
routine clinical practice provided in our endemic area because, whatever the
reason of the prescription, titers were high.
PMID- 28690736
TI - A technique for non-deflating balloon catheter removal in female patients.
AB - Removing a foley catheter can sometimes be a challenge, especially when it is
related to non-deflating balloons which represent most of the cases. In female
patients, due to their urethral anatomy, several techniques have been proposed
for balloon puncture when other maneuvers have failed. We present a simple
technique for non-deflating balloon catheter removal in an old female patient
with a permanent indwelling foley catheter which required no anesthesia. The
balloon was effectively punctured with minimal patient's discomfort. In addition,
this technique was tested in several ex-vivo model catheters and found to be safe
and effective. Our technique can be used for non-deflating balloon puncture in
female patients in an outpatient setting without anesthesia.
PMID- 28690737
TI - [Struma ovarii: a rare case of giant ovarian cyst].
AB - Struma ovarii is a rare tumor, which accounts for 2.7% of ovarian teratomas and
0.01% of ovarian tumors. It usually affects women in the fifth decades of life
and is most often detected incidentally during ultrasound and then confirmed
histologically. The gold standard treatment is surgery and prognosis is
excellent. We here report the particular case of a young female patient with
giant struma ovarii whose radiological features were classified as unusual
presentation. We match patient's data with those from the literature.
PMID- 28690738
TI - [E-Training program for sterilization in isolated military operations areas:
solution adopted by the French army].
AB - French Army Health Service provides medical support for armed forces deployed on
external missions.In order to ensure the same health care quality in the theatre
and in the metropolis, the Military Health Service provides sterilization of
reusable medical devices by its own means. Army pharmacists carrying out an on
site mission comes from different domains: medical biology laboratory, research,
medical supplies, hospital pharmacy or yet pharmaceutical laboratory for some
reservists. Training program for sterilization in isolated military operations
areas is therefore necessary in order to ensure knowledge uniformity. Our study
is organized in two parts: determination of the needs and of the adapted training
modalities, then implementation of training itself. This training should be
accessible to a geographically dispersed public whose levels of expertise in
sterilization are disparate. The module "Preparation operationnelle a la
sterilisation en Operation Exterieure" carried out allows to update and
standardize the knowledge of the deployed pharmacists. It is composed of 11 sub
modules covering the different aspects of sterilization during external missions.
Assessment using multiple-choice questions (MCQ) is necessary to check the level
of knowledge and to understanding at the end of the training. A 75% good response
rate is requested to validate the training. Training content has been approved by
the National referents for sterilization and it is already available on the e
learning platform of the Ecole du Val de Grace.
PMID- 28690739
TI - Percutaneous vertebroplasty in Moroccan patients with vertebral compression
fractures.
AB - Incidence of vertebral compression fractures (VCFs) is increasing due to the
increase in human life expectancy and prevalence of osteoporosis. Percutaneous
vertebroplasty (PVP) has become a widely used alternative treatment for
symptomatic VCFs refractory to medical therapy. It is a minimally invasive
technique involving injection most frequently of polymethylmethacrylate (PMMA)
directly into the vertebral body through the pedicles. Percutaneous
vertebroplasty yields good results in terms of early vertebral stabilization and
prompt pain relief. This study describes the experience of the Department of
Neurosurgery at Ibn Sina University Hospital (Rabat, Morocco) and assesses short
and long term clinical and radiological outcomes and complications of
vertebroplasty in a retrospective assessment of 36 vertebral compression
fractures in 35 patients (16 men and 19 women subjects) who had been treated with
vertebroplasty from November 2006 to December 2014.
PMID- 28690740
TI - [Para testicular cyst associated with a benign retro bladder cyst].
PMID- 28690741
TI - [Osteopecilia associated with psoriatic arthritis].
AB - Osteopecilia is a benign and rare condensing osteopathy. Its association with
inflammatory rheumatism is very rare. We here report the case of a 25-year old
patient with skin psoriasis, presenting with groin pain of inflammatory origin.
Physical examination showed limitation of hip motions, lower limb-length
inequality and pain on right sacroiliac mobilization. Laboratory tests showed
inflammatory syndrome and negative immunological assessment. The radiograph of
the pelvis revealed osteopecilia associated with destructive coxitis. CT scan of
the pelvis showed coxitis and osteopecilia associated with bilateral
sacroiliitis. The diagnosis of psoriatic arthritis associated with osteopecilia
was retained. The patient was treated with methotrexate and NSAIDS. Osteopecilia
usually is unexpectedly detected. Diagnostic radiology is essential to avoid
unnecessary explorations and treatments.
PMID- 28690742
TI - What factors influence the average length of stay among stroke patients in a
Nigerian tertiary hospital?
AB - INTRODUCTION: Increased emphasis is being laid on ensuring that health resources
are efficiently utilized, especially in resource-constrained settings such as in
Nigeria. One of the main indices of how efficiently a health institution is being
run is Length of Stay (LOS), which is likely to be higher in chronic diseases
such as stroke and diabetes. Stroke is a chronic disease that is currently on the
rise in Low and Middle income countries (LMICs) who are also characterized by
constraint of health resources. This study seeks to determine the LOS of stroke
patients as well as factors that affect it. METHODS: A retrospective analysis of
health records of stroke victims admitted into the medical wards of the
University College Hospital, Ibadan between January 2012 and December 2014 was
conducted. Data on sociodemographic information, comorbidities and risk factors
were extracted while LOS was calculated by counting the number of days the
patient was admitted. Analysis was carried to using SPSS. RESULTS: A total of 143
records were used in the final analysis with 53.1% of them being males and having
a mean age of 61.5 +/- 14.2 years. More than half (53.8%) of the cases were
ischemic strokes. The average length of stay was 13.7 +/- 8.9 days while
bivariate analysis showed that a greater proportion of cases who consumed
alcohol, had diabetes and hypertension had LOS of over 7 days than those who did
not. However, these differences in proportions were not statistically significant
(0.310 6 cm
from the anal verge and 61 (46%) were lower rectal cancers (LRC) - lower extent
of the tumour was palpable <= 6 cm. Circumferential resection margin (CRM)
appeared threatened on pre-operative MRI in 19/61 (31%) patients with LRC
requiring neo-adjuvant therapy (NAT). Of the 133 resections, 118 (89%) were
attempted laparoscopically (5% conversion rate). CRM was positive in 9 (6.7%)
patients; Median lymph node harvest was 12 (2-37). Major complications occurred
in 8 (6%) patients. Median follow-up was 53 mo (0-82). The 90-d mortality was 2
(1.5%). Over the follow-up period, disease related mortality was 11 (8.2%) and
overall mortality was 39 (29.3%). Four (3%) patients had local recurrence and 22
(16.5%) patients had distant metastases. CONCLUSION: Management of rectal cancers
can be optimized with multi-disciplinary input to attain acceptable long-term
oncological outcomes even when incorporating a laparoscopic approach to rectal
cancer resection.
PMID- 28690776
TI - Pilomatrixoma located on the cruris: an uncommon localization.
AB - Pilomatrixoma is a benign tumor of hair follicle matrix cells. The majority of
all pilomatrixomas were reported to affect the head-neck region and rarely the
upper extremity. We present a case of left-leg pilomatrixoma, which is a
extremely rare localization, in a 10-year-old boy.
PMID- 28690777
TI - Hemangiopericytoma of the thoracic spine: a case report.
AB - Hemangiopericytoma (HPC) has been described to be aggressive and potentially a
malignant tumour. We report a rare case of a 63-year-old Chinese male who
presented with primary intradural extramedullary HPC of the thoracic spine. The
main presenting complaint was gradual progression of back pain, associated with
paraparesis and sensory deficit of lower limbs. He had MRI thoracolumbar with
contrast which showed T9 lesion compressing on spinal cord and oedema, he was
then operated upon and histopathology report confirmed a thoracic spine HPC. A
T8/9 laminectomy and excision of intradural extramedullary lesion was performed,
tumour section was sent for frozen section study, and more tissue was sent for
paraffin studies and additional immunohistochemical staining. Surgical resection
is most commonly performed, radiotherapy remains debatable. In this report, we
discussed another rare case of primary spinal HPC to be added into the
literature.
PMID- 28690778
TI - Vacuum-assisted closure therapy after resection of giant basal cell carcinoma of
the scalp.
AB - Management of complicated wounds is a challenge in head and neck reconstruction.
Although the negative pressure wound therapy or wound vacuum-assisted closure has
been widely used in complicated wounds and shows promising results, its
application in the head and neck region after reconstruction for the head and
neck cancer is rarely presented. A 77-year-old woman underwent a radical
resection of an extensive basal cell carcinoma of the scalp and forehead
involving the periosteum, where classic reconstruction was difficult, but
successfully treated with negative pressure wound therapy. Negative pressure
wound therapy is an efficacious tool in cases of complex and extensive defects,
when we expect immediate reconstruction with poor results, as would be probable
with this scalp lesion.
PMID- 28690780
TI - Alpine glacier-fed turbid lakes are discontinuous cold polymictic rather than
dimictic.
AB - Glacier retreat as a consequence of climate change influences freshwater
ecosystems in manifold ways, yet the physical and chemical bases of these effects
are poorly studied. Here, we characterize how water temperature differs between
alpine lakes with and without direct glacier influence on seasonal and diurnal
timescales. Using high temporal resolution monitoring of temperature in 4 lakes
located in a catchment influenced by glacier retreat, we reported unexpectedly
high surface temperatures, even in proglacial lakes located 2600 m a.s.l. Cold
glacier meltwater and low nighttime air temperatures caused a distinct diurnal
pattern of water temperature in the water column of glacier-influenced lakes.
Precipitation onto glacier surfaces apparently leads to rapid cooling of the
glacier-fed lakes and disrupts the thermal stratification with several mixing
events during the summer. Taken together, these mechanisms contribute to the
unique seasonal and diurnal dynamics of glacier-influenced lakes that contrast
with the typical dimictic pattern of clear alpine lakes and represent an example
of discontinuous cold polymictic lake type. This work contributes to the basic
description of how climate and meteorology affect the physical properties of an
increasingly common lake type.
PMID- 28690781
TI - Bioaccumulation of ultraviolet sunscreen compounds (mycosporine-like amino acids)
by the heterotrophic freshwater ciliate Bursaridium living in alpine lakes.
AB - Ciliates in shallow alpine lakes are exposed to high levels of incident solar
ultraviolet radiation (UVR). We observed the presence of specific sunscreen
compounds, the mycosporine-like amino acids (MAAs), in several populations of
Bursaridium, a relatively large ciliate species found in such lakes. The
populations from 3 highly UV transparent lakes revealed the presence of 7 MAAs
(MG, SH, PR, PI, AS, US, and PE) in total concentrations of 3.6-52.4 10-5 MUg MUg
1 dry weight (DW) per individual, whereas in one glacially turbid and less UV
transparent lake, no MAAs were detected in the Bursaridium population. The MAAs
in the ciliates generally reflected the composition and relative amounts of the
lakes' seston MAAs, assuming that the ciliates fed on MAA-rich plankton. We
experimentally found that naturally acquired MAAs prevented ciliate mortality
under simulated UVR and photosynthetically active radiation (PAR) conditions. We
further tested the dietary regulation of the MAAs-content in the ciliates under
artificial UVR and PAR exposure and found an increase in MAAs concentrations in
all treatments. Our assumption was that several stress factors other than
irradiation were involved in the synthesis or up-regulation of MAAs.
PMID- 28690782
TI - Sequential learning in individuals with agrammatic aphasia: evidence from
artificial grammar learning.
AB - We examined sequential learning in individuals with agrammatic aphasia (n = 12)
and healthy age-matched participants (n = 12) using an artificial grammar.
Artificial grammar acquisition, 24-hour retention, and the potential benefits of
additional training were examined by administering an artificial grammar judgment
test (1) immediately following auditory exposure-based training, (2) one day
after training, and (3) after a second training session on the second day. An
untrained control group (n = 12 healthy age-matched participants) completed the
tests on the same time schedule. The trained healthy and aphasic groups showed
greater sensitivity to the detection of grammatical items than the control group.
No significant correlations between sequential learning and language abilities
were observed among the aphasic participants. The results suggest that
individuals with agrammatic aphasia show sequential learning, but the underlying
processes involved in this learning may be different than for healthy adults.
PMID- 28690783
TI - Invasive plant species in the West Indies: geographical, ecological, and
floristic insights.
AB - The level of invasion (number or proportion of invasive species) in a given area
depends on features of the invaded community, propagule pressure, and climate. In
this study, we assess the invasive flora of nine islands in the West Indies to
identify invasion patterns and evaluate whether invasive species diversity is
related to geographical, ecological, and socioeconomic factors. We compiled a
database of invasive plant species including information on their taxonomy,
origin, pathways of introduction, habitats, and life history. This database was
used to evaluate the similarity of invasive floras between islands and to
identify invasion patterns at regional (West Indies) and local (island) scales.
We found a total of 516 alien plant species that are invasive on at least one of
the nine islands studied, with between 24 to 306 invasive species per island. The
invasive flora on these islands includes a wide range of taxonomic groups, life
forms, and habitats. We detected low similarity in invasive species diversity
between islands, with most invasive species (>60%) occurring on a single island
and 6% occurring on at least five islands. To assess the importance of different
models in predicting patterns of invasive species diversity among islands, we
used generalized linear models. Our analyses revealed that invasive species
diversity was well predicted by a combination of island area and economic
development (gross domestic product per capita and kilometers of paved roadways).
Our results provide strong evidence for the roles of geographical, ecological,
and socioeconomic factors in determining the distribution and spread of invasive
species on these islands. Anthropogenic disturbance and economic development seem
to be the major drivers facilitating the spread and predominance of invasive
species over native species.
PMID- 28690784
TI - Winter is coming: Food web structure and seasonality in a subtropical freshwater
coastal lake.
AB - Food web studies provide a useful tool to assess the organization and complexity
of natural communities. Nevertheless, the seasonal dynamics of food web
properties, their environmental correlates, and potential association with
community diversity and stability remain poorly studied. Here, we condensed an
incomplete 6-year community dataset of a subtropical coastal lake to examine how
monthly variation in diversity impacts food web structure over an idealized time
series for an averaged year. Phytoplankton, zooplankton, macroinvertebrates, and
fish were mostly resolved to species level (n = 120 trophospecies). Our results
showed that the seasonal organization of the food web could be aggregated into
two clusters of months grouped here as 'summer' and 'winter'. During 'winter',
the food web decreases in size and complexity, with the number of trophospecies
dropping from 106 to 82 (a 22.6% decrease in the number of nodes) and the trophic
interactions from 1,049 to 637 between month extremes (a 39.3% drop in the number
of links). The observed simplification in food web structure during 'winter'
suggests that community stability is more vulnerable to the impact of any change
during this period.
PMID- 28690785
TI - Rates and relations of mitochondrial genome evolution across the Echinoidea, with
special focus on the superfamily Odontophora.
AB - In order to better characterize the placement of genus Tripneustes, as a
representative of the Toxopneustidae family within the broader sea urchin
mitochondrial (MT) phylogeny, the complete MT genome of Tripneustes gratilla was
generated and compared with all published echinoid MT genomes currently available
on NCBI GenBank. The MT genome phylogeny supports the existence of the
superfamily Odontophora (consisting of the families Strongylocentrotidae,
Echinometridae, and Toxopneustidae). A relaxed molecular-clock time calibration
suggests a split between the three key Odontophore MT lineages occurred during
the late Eocene/Oligocene. Major global oceanographic changes have been inferred
during this time frame, potentially driving species diversification through
environmental selection pressures. To test for signatures of selection acting on
the mitochondria, the historical rate of gene evolution of individual MT genes
was assessed through a branch-site comparison of nonsynonymous to synonymous
substitution ratios (omega). Models of positive selection and neutral evolution,
as compared via a likelihood ratio test, show no evidence of strong historical
positive selection on mitochondrial genes at the genesis of the Odontophora.
However, while pairwise omega comparison revealed signatures of strong negative
selection, relatively elevated omega values were observed within the
Strongylocentrotus genus.
PMID- 28690786
TI - Remote sensing-based landscape indicators for the evaluation of threatened-bird
habitats in a tropical forest.
AB - Avian species persistence in a forest patch is strongly related to the degree of
isolation and size of a forest patch and the vegetation structure within a patch
and its matrix are important predictors of bird habitat suitability. A
combination of space-borne optical (Landsat), ALOS-PALSAR (radar), and airborne
Light Detection and Ranging (LiDAR) data was used for assessing variation in
forest structure across forest patches that had undergone different levels of
forest degradation in a logged forest-agricultural landscape in Southern Laos.
The efficacy of different remote sensing (RS) data sources in distinguishing
forest patches that had different seizes, configurations, and vegetation
structure was examined. These data were found to be sensitive to the varying
levels of degradation of the different patch categories. Additionally, the role
of local scale forest structure variables (characterized using the different RS
data and patch area) and landscape variables (characterized by distance from
different forest patches) in influencing habitat preferences of International
Union for Conservation of Nature (IUCN) Red listed birds found in the study area
was examined. A machine learning algorithm, MaxEnt, was used in conjunction with
these data and field collected geographical locations of the avian species to
identify the factors influencing habitat preference of the different bird species
and their suitable habitats. Results show that distance from different forest
patches played a more important role in influencing habitat suitability for the
different avian species than local scale factors related to vegetation structure
and health. In addition to distance from forest patches, LiDAR-derived forest
structure and Landsat-derived spectral variables were important determinants of
avian habitat preference. The models derived using MaxEnt were used to create an
overall habitat suitability map (HSM) which mapped the most suitable habitat
patches for sustaining all the avian species. This work also provides insight
that retention of forest patches, including degraded and isolated forest patches
in addition to large contiguous forest patches, can facilitate bird species
retention within tropical agricultural landscapes. It also demonstrates the
effective use of RS data in distinguishing between forests that have undergone
varying levels of degradation and identifying the habitat preferences of
different bird species. Practical conservation management planning endeavors can
use such data for both landscape scale monitoring and habitat mapping.
PMID- 28690787
TI - The effects of historical fragmentation on major histocompatibility complex class
II beta and microsatellite variation in the Aegean island reptile, Podarcis
erhardii.
AB - The major histocompatibility complex (MHC) plays a key role in disease resistance
and is the most polymorphic gene region in vertebrates. Although habitat
fragmentation is predicted to lead to a loss in MHC variation through drift, the
impact of other evolutionary forces may counter this effect. Here we assess the
impact of selection, drift, migration, and recombination on MHC class II and
microsatellite variability in 14 island populations of the Aegean wall lizard
Podarcis erhardii. Lizards were sampled from islands within the Cyclades (Greece)
formed by rising sea levels as the last glacial maximum approximately 20,000
before present. Bathymetric data were used to determine the area and age of each
island, allowing us to infer the corresponding magnitude and timing of genetic
bottlenecks associated with island formation. Both MHC and microsatellite
variation were positively associated with island area, supporting the hypothesis
that drift governs neutral and adaptive variation in this system. However, MHC
but not microsatellite variability declined significantly with island age. This
discrepancy is likely due to the fact that microsatellites attain mutation-drift
equilibrium more rapidly than MHC. Although we detected signals of balancing
selection, recombination and migration, the effects of these evolutionary
processes appeared negligible relative to drift. This study demonstrates how land
bridge islands can provide novel insights into the impact of historical
fragmentation on genetic diversity as well as help disentangle the effects of
different evolutionary forces on neutral and adaptive diversity.
PMID- 28690788
TI - Effects of local biotic neighbors and habitat heterogeneity on seedling survival
in a spruce-fir valley forest, northeastern China.
AB - Seedlings are vulnerable to many biotic and abiotic agents, and studying seedling
dynamics helps understand mechanisms of species coexistence. In this study, the
relative importance of biotic neighbors and habitat heterogeneity to seedling
survival was examined by generalized linear mixed models for 33 species in a
spruce-fir valley forest in northeastern China. The results showed that the
relative importance of these factors varied with species and functional groups.
Conspecific negative density dependence (CNDD) was important to the survival of
Abies nephrolepis and Picea koraiensis seedling, whereas phylogenetic negative
density dependence (PNDD) was critical to Pinus koraiensis and Betula
platyphylla, as well as functional groups of tree, deciduous, and shade
intolerant seedlings. For shrubs and Acer ukurunduense, habitat heterogeneity was
significant. Despite of the significance of CNDD, PNDD, and habitat heterogeneity
on seedling survival, large proportions of the total variance were not accounted
for by the studied variables, suggesting the needs to examine the influences of
other factors such as pests, diseases, herbivores, forest structure, species
functional traits, and microclimatic conditions on seedling survival in the
future.
PMID- 28690789
TI - Bring your own camera to the trap: An inexpensive, versatile, and portable
triggering system tested on wild hummingbirds.
AB - The study of animals in the wild offers opportunities to collect relevant
information on their natural behavior and abilities to perform ecologically
relevant tasks. However, it also poses challenges such as accounting for observer
effects, human sensory limitations, and the time intensiveness of this type of
research. To meet these challenges, field biologists have deployed camera traps
to remotely record animal behavior in the wild. Despite their ubiquity in
research, many commercial camera traps have limitations, and the species and
behavior of interest may present unique challenges. For example, no camera traps
support high-speed video recording. We present a new and inexpensive camera trap
system that increases versatility by separating the camera from the triggering
mechanism. Our system design can pair with virtually any camera and allows for
independent positioning of a variety of sensors, all while being low-cost,
lightweight, weatherproof, and energy efficient. By using our specialized trigger
and customized sensor configurations, many limitations of commercial camera traps
can be overcome. We use this system to study hummingbird feeding behavior using
high-speed video cameras to capture fast movements and multiple sensors placed
away from the camera to detect small body sizes. While designed for hummingbirds,
our application can be extended to any system where specialized camera or sensor
features are required, or commercial camera traps are cost-prohibitive, allowing
camera trap use in more research avenues and by more researchers.
PMID- 28690790
TI - Recent upgrades of the harmonic radar for the tracking of the Asian yellow-legged
hornet.
AB - The yellow-legged Asian hornet is an invasive species of wasps, indigenous of the
South-East Asia but quickly spreading in Southern Europe. Because of its
exponential diffusion and its serious threat to the local honey bee colonies and
to humans as well, restraint measures are under investigation. Among them, the
harmonic radar described in (Ecology and Evolution, 6, 2016 and 2170) already
proved to be a quite effective way to follow the hornets to their nests; it is in
fact capable of tracking the flying trajectory of these insects, once equipped
with a small transponder, in their natural environment. The aforementioned
harmonic radar was upgraded after a period of intense experimentation; the
capture of the hornets was enhanced as well, and other improvements were adopted
in the mounting procedure of the transponder. Thanks to these upgrades, the
flying capabilities of the hornets were not reduced and a huge collection of data
was recorded. The main upgrade to the radar was the adoption of the vertical
polarization of the radiated field, with the consequent redesign and
manufacturing of the antennas and the different mounting of the transceiver on
the insect. The installation of the radar on a telescopic tower drastically
improved the maneuverability of the system and the capability to follow the
insects' preferential flying directions. Eventually, the system was able to
produce much more continuous traces with a clear indication of the most probable
position of the nest. The maximum range of detection was also increased to 150 m.
PMID- 28690791
TI - Bioclimatic transect networks: Powerful observatories of ecological change.
AB - Transects that traverse substantial climate gradients are important tools for
climate change research and allow questions on the extent to which phenotypic
variation associates with climate, the link between climate and species
distributions, and variation in sensitivity to climate change among biomes to be
addressed. However, the potential limitations of individual transect studies have
recently been highlighted. Here, we argue that replicating and networking
transects, along with the introduction of experimental treatments, addresses
these concerns. Transect networks provide cost-effective and robust insights into
ecological and evolutionary adaptation and improve forecasting of ecosystem
change. We draw on the experience and research facilitated by the Australian
Transect Network to demonstrate our case, with examples, to clarify how
population- and community-level studies can be integrated with observations from
multiple transects, manipulative experiments, genomics, and ecological modeling
to gain novel insights into how species and systems respond to climate change.
This integration can provide a spatiotemporal understanding of past and future
climate-induced changes, which will inform effective management actions for
promoting biodiversity resilience.
PMID- 28690792
TI - The most common diet results in low reproduction in a generalist seabird.
AB - Dietary specialization has been described across a wide range of taxa in the
animal kingdom. Fitness consequences are, however, not well documented. We
examined the reproductive consequences of different dietary specializations in
the herring gull Larus argentatus, an omnivorous seabird, using an extensive
dataset which includes breeding and dietary data of 10 successive years. We
hypothesized that pairs that focused on prey of higher energetic value would
yield higher fledging rates. An alternative hypothesis is that pairs that relied
on more resources simultaneously would reproduce better. The novelty of this
study is that we used continuous measurements representing dietary composition
and degree of specialization rather than restricting our analysis to predefined
categories. By relating these two continuous measurements for diet to several
proxies for reproductive success, we show clear consequences of dietary choice.
Most pairs concentrated on bivalves, a prey type not particularly rich in energy.
Pairs feeding on energy-rich prey (e.g., "domestic refuse and fishery discards")
during chick rearing were found to have a higher reproductive success, supporting
the first hypothesis. Pairs that used more resources did not clearly have a
higher reproductive success. The majority of the pairs did not switch to energy
rich prey during chick rearing, despite low breeding outcome. We discuss how
trade-offs between factors such as resource availability, predictability, and the
time and energy needed to obtain certain prey species may influence resource
selection.
PMID- 28690793
TI - Postfire soil water repellency in pinon-juniper woodlands: Extent, severity, and
thickness relative to ecological site characteristics and climate.
AB - Wildfires can create or intensify water repellency in soil, limiting the soil's
capacity to wet and retain water. The objective of this research was to quantify
soil water repellency characteristics within burned pinon-juniper woodlands and
relate this information to ecological site characteristics. We sampled soil water
repellency across forty-one 1,000 m2 study plots within three major wildfires
that burned in pinon-juniper woodlands. Water repellency was found to be
extensive-present at 37% of the total points sampled-and strongly related to
pinon-juniper canopy cover. Models developed for predicting SWR extent and
severity had R2adj values of 0.67 and 0.61, respectively; both models included
pinon-juniper canopy cover and relative humidity the month before the fire as
coefficient terms. These results are important as they suggest that postfire
water repellency will increase in the coming years as infilling processes enhance
pinon-juniper canopy cover. Furthermore, reductions in relative humidity brought
about by a changing climate have the potential to link additively with infilling
processes to increase the frequency and intensity of wildfires and produce
stronger water repellency over a greater spatial extent. In working through these
challenges, land managers can apply the predictive models developed in this study
to prioritize fuel control and postfire restoration treatments.
PMID- 28690794
TI - An evaluation of semi-automated methods for collecting ecosystem-level data in
temperate marine systems.
AB - Historically, marine ecologists have lacked efficient tools that are capable of
capturing detailed species distribution data over large areas. Emerging
technologies such as high-resolution imaging and associated machine-learning
image-scoring software are providing new tools to map species over large areas in
the ocean. Here, we combine a novel diver propulsion vehicle (DPV) imaging system
with free-to-use machine-learning software to semi-automatically generate dense
and widespread abundance records of a habitat-forming algae over ~5,000 m2 of
temperate reef. We employ replicable spatial techniques to test the effectiveness
of traditional diver-based sampling, and better understand the distribution and
spatial arrangement of one key algal species. We found that the effectiveness of
a traditional survey depended on the level of spatial structuring, and generally
10-20 transects (50 * 1 m) were required to obtain reliable results. This
represents 2-20 times greater replication than have been collected in previous
studies. Furthermore, we demonstrate the usefulness of fine-resolution
distribution modeling for understanding patterns in canopy algae cover at
multiple spatial scales, and discuss applications to other marine habitats. Our
analyses demonstrate that semi-automated methods of data gathering and processing
provide more accurate results than traditional methods for describing habitat
structure at seascape scales, and therefore represent vastly improved techniques
for understanding and managing marine seascapes.
PMID- 28690795
TI - Short-term effect of elevated CO2 concentration (0.5%) on mitochondria in diploid
and tetraploid black locust (Robinia pseudoacacia L.).
AB - Recent increases in atmospheric CO 2 concentration have affected the growth and
physiology of plants. In this study, plants were grown with 0.5% CO 2 for 0, 3,
and 6 days. The anatomy, fluorescence intensity of H2O2, respiration rate, and
antioxidant activities of the mitochondria were analyzed in diploid (2*) and
tetraploid (4*) black locust (Robinia pseudoacacia L.). Exposure to 0.5% CO 2
resulted in clear structural alterations and stomatal closure in the
mitochondria. Reduced membrane integrity and increased structural damage were
observed in 2* plants at 6 days. However, after 0.5% CO 2 treatment, little
structural damage was observed in 4* plants. Under severe stress, H2O2 and
malondialdehyde were dramatically induced in both 2* and 4* plants. Proline
remains unchanged at an elevated CO 2 concentration in 4* plants. Moreover, the
total respiration and alternative respiration rates decreased in both 2* and 4*
plants. In contrast, the cytochrome pathway showed no decrease in 2* plants and
even increased slightly in 4* plants. The antioxidant enzymes and nonenzymatic
antioxidants, which are related to the ascorbate-glutathione pathway, were
inhibited following CO 2 exposure. These analyses indicated that 4* and 2* plants
were damaged by 0.5% CO 2 but the former were more resistant than the latter, and
this may be due to increases in antioxidant enzymes and nonenzymatic antioxidants
and stabilized membrane structure.
PMID- 28690796
TI - A novel method of caenophidian snake sex identification using molecular markers
based on two gametologous genes.
AB - Sex identification provides important information for ecological and evolutionary
studies, as well as benefiting snake conservation management. Traditional methods
such as cloacal probing or cloacal popping are counterproductive for sex
identification concerning very small species, resulting in difficulties in the
management of their breeding programs. In this study, the nucleotide sequences of
gametologous genes (CTNNB1 and WAC genes) were used for the development of
molecular sexing markers in caenophidian snakes. Two candidate markers were
developed with the two primer sets, and successfully amplified by a single band
on the agarose gel in male (ZZ) and two bands, differing in fragment sizes, in
female (ZW) of 16 caenophidian snakes for CTNNB1 and 12 caenophidian snakes for
WAC. Another candidate marker was developed with the primer set to amplify the
specific sequence for CTNNB1W homolog, and the PCR products were successfully
obtained in a female-specific 250-bp DNA bands. The three candidate PCR sexing
markers provide a simple sex identification method based on the amplification of
gametologous genes, and they can be used to facilitate effective caenophidian
snake conservation and management programs.
PMID- 28690797
TI - The influence of breeding phenology on the genetic structure of four pond
breeding salamanders.
AB - Understanding metapopulation dynamics requires knowledge about local population
dynamics and movement in both space and time. Most genetic metapopulation studies
use one or two study species across the same landscape to infer population
dynamics; however, using multiple co-occurring species allows for testing of
hypotheses related to different life history strategies. We used genetic data to
study dispersal, as measured by gene flow, in three ambystomatid salamanders
(Ambystoma annulatum, A. maculatum, and A. opacum) and the Central Newt
(Notophthalmus viridescens louisianensis) on the same landscape in Missouri, USA.
While all four salamander species are forest dependent organisms that require
fishless ponds to reproduce, they differ in breeding phenology and spatial
distribution on the landscape. We use these differences in life history and
distribution to address the following questions: (1) Are there species-level
differences in the observed patterns of genetic diversity and genetic structure?
and (2) Is dispersal influenced by landscape resistance? We detected two genetic
clusters in A. annulatum and A. opacum on our landscape; both species breed in
the fall and larvae overwinter in ponds. In contrast, no structure was evident in
A. maculatum and N. v. louisianensis, species that breed during the spring. Tests
for isolation by distance were significant for the three ambystomatids but not
for N. v. louisianensis. Landscape resistance also contributed to genetic
differentiation for all four species. Our results suggest species-level
differences in dispersal ability and breeding phenology are driving observed
patterns of genetic differentiation. From an evolutionary standpoint, the
observed differences in dispersal distances and genetic structure between fall
breeding and spring breeding species may be a result of the trade-off between
larval period length and size at metamorphosis which in turn may influence the
long-term viability of the metapopulation. Thus, it is important to consider life
history differences among closely related and ecologically similar species when
making management decisions.
PMID- 28690798
TI - Differential impacts of shared parasites on fitness components among competing
hosts.
AB - Effects of parasites on individual hosts can eventually translate to impacts on
host communities. In particular, parasitism can differentially affect host
fitness among sympatric and interacting host species. We examined whether the
impact of shared parasites varied among host species within the same community.
Specifically, we looked at the impacts of the acanthocephalan Acanthocephalus
galaxii, the trematodes Coitocaecum parvum and Maritrema poulini, and the
nematode Hedruris spinigera, on three host species: the amphipods, Paracalliope
fluviatilis and Paracorophium excavatum, and the isopod, Austridotea annectens.
We assessed parasite infection levels in the three host species and tested for
effects on host survival, behavior, probability of pairing, and fecundity.
Maritrema poulini and C. parvum were most abundant in P. excavatum but had no
effect on its survival, whereas they negatively affected the survival of P.
fluviatilis, the other amphipod. Female amphipods carrying young had higher M.
poulini and C. parvum abundance than those without, yet the number of young
carried was not linked to parasite abundance. Behavior of the isopod A. annectens
was affected by M. poulini infection; more heavily infected individuals were more
active. Paracorophium excavatum moved longer distances when abundance of C.
parvum was lower, yet no relationship existed with respect to infection by both
M. poulini and C. parvum. The differential effects of parasites on amphipods and
isopods may lead to community-wide effects. Understanding the consequences of
parasitic infection and differences among host species is key to gaining greater
insight into the role of parasite mediation in ecosystem dynamics.
PMID- 28690799
TI - Sex-biased oviposition by a nursery pollinator on a gynodioecious host plant:
Implications for breeding system evolution and evolution of mutualism.
AB - Dioecy, a breeding system where individual plants are exclusively male or female,
has evolved repeatedly. Extensive theory describes when dioecy should arise from
hermaphroditism, frequently through gynodioecy, where females and hermaphrodites
coexist, and when gynodioecy should be stable. Both pollinators and herbivores
often prefer the pollen-bearing sex, with sex-specific fitness effects that can
affect breeding system evolution. Nursery pollination, where adult insects
pollinate flowers but their larvae feed on plant reproductive tissues, is a model
for understanding mutualism evolution but could also yield insights into plant
breeding system evolution. We studied a recently established nursery pollination
interaction between native Hadena ectypa moths and introduced gynodioecious
Silene vulgaris plants in North America to assess whether oviposition was biased
toward females or hermaphrodites, which traits were associated with oviposition,
and the effect of oviposition on host plant fitness. Oviposition was
hermaphrodite-biased and associated with deeper flowers and more stems. Sexual
dimorphism in flower depth, a trait also associated with oviposition on the
native host plant (Silene stellata), explained the hermaphrodite bias. Egg
receiving plants experienced more fruit predation than plants that received no
eggs, but relatively few fruits were lost, and egg receipt did not significantly
alter total fruit production at the plant level. Oviposition did not enhance
pollination; egg-receiving flowers usually failed to expand and produce seeds.
Together, our results suggest that H. ectypa oviposition does not exert a large
fitness cost on host plants, sex-biased interactions can emerge from preferences
developed on a hermaphroditic host species, and new nursery pollination
interactions can arise as negative or neutral rather than as mutualistic for the
plant.
PMID- 28690800
TI - Do plant populations on distinct inselbergs talk to each other? A case study of
genetic connectivity of a bromeliad species in an Ocbil landscape.
AB - Here, we explore the historical and contemporaneous patterns of connectivity
among Encholirium horridum populations located on granitic inselbergs in an Ocbil
landscape within the Brazilian Atlantic Forest, using both nuclear and
chloroplast microsatellite markers. Beyond to assess the E. horridum population
genetic structure, we built species distribution models across four periods
(current conditions, mid-Holocene, Last Glacial Maximum [LGM], and Last
Interglacial) and inferred putative dispersal corridors using a least-cost path
analysis to elucidate biogeographic patterns. Overall, high and significant
genetic divergence was estimated among populations for both nuclear and plastid
DNA (PhiST(n) = 0.463 and PhiST(plastid) = 0.961, respectively, p < .001). For
nuclear genome, almost total absence of genetic admixture among populations and
very low migration rates were evident, corroborating with the very low estimates
of immigration and emigration rates observed among E. horridum populations. Based
on the cpDNA results, putative dispersal routes in Sugar Loaf Land across cycles
of climatic fluctuations in the Quaternary period revealed that the populations'
connectivity changed little during those events. Genetic analyses highlighted the
low genetic connectivity and long-term persistence of populations, and the
founder effect and genetic drift seemed to have been very important processes
that shaped the current diversity and genetic structure observed in both genomes.
The genetic singularity of each population clearly shows the need for in situ
conservation of all of them.
PMID- 28690801
TI - Single nucleotide polymorphism barcoding of cytochrome c oxidase I sequences for
discriminating 17 species of Columbidae by decision tree algorithm.
AB - DNA barcodes are widely used in taxonomy, systematics, species identification,
food safety, and forensic science. Most of the conventional DNA barcode sequences
contain the whole information of a given barcoding gene. Most of the sequence
information does not vary and is uninformative for a given group of taxa within a
monophylum. We suggest here a method that reduces the amount of noninformative
nucleotides in a given barcoding sequence of a major taxon, like the prokaryotes,
or eukaryotic animals, plants, or fungi. The actual differences in genetic
sequences, called single nucleotide polymorphism (SNP) genotyping, provide a tool
for developing a rapid, reliable, and high-throughput assay for the
discrimination between known species. Here, we investigated SNPs as robust
markers of genetic variation for identifying different pigeon species based on
available cytochrome c oxidase I (COI) data. We propose here a decision tree
based SNP barcoding (DTSB) algorithm where SNP patterns are selected from the DNA
barcoding sequence of several evolutionarily related species in order to identify
a single species with pigeons as an example. This approach can make use of any
established barcoding system. We here firstly used as an example the
mitochondrial gene COI information of 17 pigeon species (Columbidae, Aves) using
DTSB after sequence trimming and alignment. SNPs were chosen which followed the
rule of decision tree and species-specific SNP barcodes. The shortest barcode of
about 11 bp was then generated for discriminating 17 pigeon species using the
DTSB method. This method provides a sequence alignment and tree decision approach
to parsimoniously assign a unique and shortest SNP barcode for any known species
of a chosen monophyletic taxon where a barcoding sequence is available.
PMID- 28690802
TI - Unraveling the relative contribution of inter- and intrapopulation functional
variability in wild populations of a tadpole species.
AB - Functional traits are increasingly recognized as an integrative approach by
ecologists to quantify a key facet of biodiversity. And these traits are
primarily expressed as species means in previous studies, based on the assumption
that the effects of intraspecific variability can be overridden by interspecific
variability when studying functional ecology at the community level. However,
given that intraspecific variability could also have important effects on
community dynamics and ecosystem functioning, empirical studies are needed to
investigate the importance of intraspecific variability in functional traits. In
this study, 256 Scutiger boulengeri tadpole individuals from four different
populations are used to quantify the functional difference between populations
within a species, and the relative contribution of inter- and intrapopulation
variability in functional traits. Our results demonstrate that these four
populations differ significantly in functional attributes (i.e., functional
position, functional richness, and low functional overlap), indicating that
individuals from different populations within a species should be explicitly
accounted for in functional studies. We also find similar relative contribution
of inter- (~56%) and intrapopulation (~44%) variation to the total variability
between individuals, providing evidence that individuals within populations
should also be incorporated in functional studies. Overall, our results support
the recent claims that intraspecific variability cannot be ignored, as well as
the general idea of "individual level" research in functional ecology.
PMID- 28690803
TI - Deriving a light use efficiency estimation algorithm using in situ hyperspectral
and eddy covariance measurements for a maize canopy in Northeast China.
AB - We estimated the light use efficiency (LUE) via vegetation canopy chlorophyll
content (CCCcanopy) based on in situ measurements of spectral reflectance,
biophysical characteristics, ecosystem CO 2 fluxes and micrometeorological
factors over a maize canopy in Northeast China. The results showed that among the
common chlorophyll-related vegetation indices (VIs), CCCcanopy had the most
obviously exponential relationships with the red edge position (REP) (R2 = .97, p
< .001) and normalized difference vegetation index (NDVI) (R2 = .91, p < .001).
In a comparison of the indicating performances of NDVI, ratio vegetation index
(RVI), wide dynamic range vegetation index (WDRVI), and 2-band enhanced
vegetation index (EVI2) when estimating CCCcanopy using all of the possible
combinations of two separate wavelengths in the range 400-1300 nm, EVI2 [1214,
1259] and EVI2 [726, 1248] were better indicators, with R2 values of .92 and .90
(p < .001). Remotely monitoring LUE through estimating CCCcanopy derived from
field spectrometry data provided accurate prediction of midday gross primary
productivity (GPP) in a rainfed maize agro-ecosystem (R2 = .95, p < .001). This
study provides a new paradigm for monitoring vegetation GPP based on the
combination of LUE models with plant physiological properties.
PMID- 28690804
TI - Factors shaping community assemblages and species co-occurrence of different
trophic levels.
AB - Species assemblages are the results of various processes, including dispersion
and habitat filtering. Disentangling the effects of these different processes is
challenging for statistical analysis, especially when biotic interactions should
be considered. In this study, we used plants (producers) and leafhoppers
(phytophagous) as model organisms, and we investigated the relative importance of
abiotic versus biotic factors that shape community assemblages, and we infer on
their biotic interactions by applying three-step statistical analysis. We applied
a novel statistical analysis, that is, multiblock Redundancy Analysis (mbRA, step
1) and showed that 51.8% and 54.1% of the overall variation in plant and
leafhopper assemblages are, respectively, explained by the two multiblock models.
The most important blocks of variables to explain the variations in plant and
leafhopper assemblages were local topography and biotic factors. Variation
partitioning analysis (step 2) showed that pure abiotic filtering and pure biotic
processes were relatively less important than their combinations, suggesting that
biotic relationships are strongly structured by abiotic conditions. Pairwise co
occurrence analysis (step 3) on generalist leafhoppers and the most common plants
identified 40 segregated species pairs (mainly between plant species) and 16
aggregated pairs (mainly between leafhopper species). Pairwise analysis on
specialist leafhoppers and potential host plants clearly revealed aggregated
patterns. Plant segregation suggests heterogeneous resource availability and
competitive interactions, while leafhopper aggregation suggests host feeding
differentiation at the local level, different feeding microhabitats on host
plants, and similar environmental requirements of the species. Using the novel
mbRA, we disentangle for the first time the relative importance of more than five
distinct groups of variables shaping local species communities. We highlighted
the important role of abiotic processes mediated by bottom-up effects of plants
on leafhopper communities. Our results revealed that in-field structure
diversification and trophic interactions are the main factors causing the co
occurrence patterns observed.
PMID- 28690805
TI - Evaluating hybridization capture with RAD probes as a tool for museum genomics
with historical bird specimens.
AB - Laboratory techniques for high-throughput sequencing have enhanced our ability to
generate DNA sequence data from millions of natural history specimens collected
prior to the molecular era, but remain poorly tested at shallower evolutionary
time scales. Hybridization capture using restriction site-associated DNA probes
(hyRAD) is a recently developed method for population genomics with museum
specimens. The hyRAD method employs fragments produced in a restriction site
associated double digestion as the basis for probes that capture orthologous loci
in samples of interest. While promising in that it does not require a reference
genome, hyRAD has yet to be applied across study systems in independent
laboratories. Here, we provide an independent assessment of the effectiveness of
hyRAD on both fresh avian tissue and dried tissue from museum specimens up to 140
years old and investigate how variable quantities of input DNA affect sequencing,
assembly, and population genetic inference. We present a modified bench protocol
and bioinformatics pipeline, including three steps for detection and removal of
microbial and mitochondrial DNA contaminants. We confirm that hyRAD is an
effective tool for sampling thousands of orthologous SNPs from historic museum
specimens to describe phylogeographic patterns. We find that modern DNA performs
significantly better than historical DNA better during sequencing but that
assembly performance is largely equivalent. We also find that the quantity of
input DNA predicts %GC content of assembled contiguous sequences, suggesting PCR
bias. We caution against sampling schemes that include taxonomic or geographic
autocorrelation across modern and historic samples.
PMID- 28690806
TI - World without borders-genetic population structure of a highly migratory marine
predator, the blue shark (Prionace glauca).
AB - Highly migratory, cosmopolitan oceanic sharks often exhibit complex movement
patterns influenced by ontogeny, reproduction, and feeding. These elusive species
are particularly challenging to population genetic studies, as representative
samples suitable for inferring genetic structure are difficult to obtain. Our
study provides insights into the genetic population structure one of the most
abundant and wide-ranging oceanic shark species, the blue shark Prionace glauca,
by sampling the least mobile component of the populations, i.e., young-of-year
and small juveniles (<2 year; N = 348 individuals), at three reported nursery
areas, namely, western Iberia, Azores, and South Africa. Samples were collected
in two different time periods (2002-2008 and 2012-2015) and were screened at 12
nuclear microsatellites and at a 899-bp fragment of the mitochondrial control
region. Our results show temporally stable genetic homogeneity among the three
Atlantic nurseries at both nuclear and mitochondrial markers, suggesting basin
wide panmixia. In addition, comparison of mtDNA CR sequences from Atlantic and
Indo-Pacific locations also indicated genetic homogeneity and unrestricted female
mediated gene flow between ocean basins. These results are discussed in light of
the species' life history and ecology, but suggest that blue shark populations
may be connected by gene flow at the global scale. The implications of the
present findings to the management of this important fisheries resource are also
discussed.
PMID- 28690807
TI - The landscape of fear as an emergent property of heterogeneity: Contrasting
patterns of predation risk in grassland ecosystems.
AB - The likelihood of encountering a predator influences prey behavior and spatial
distribution such that non-consumptive effects can outweigh the influence of
direct predation. Prey species are thought to filter information on perceived
predator encounter rates in physical landscapes into a landscape of fear defined
by spatially explicit heterogeneity in predation risk. The presence of multiple
predators using different hunting strategies further complicates navigation
through a landscape of fear and potentially exposes prey to greater risk of
predation. The juxtaposition of land cover types likely influences overlap in
occurrence of different predators, suggesting that attributes of a landscape of
fear result from complexity in the physical landscape. Woody encroachment in
grasslands furnishes an example of increasing complexity with the potential to
influence predator distributions. We examined the role of vegetation structure on
the distribution of two avian predators, Red-tailed Hawk (Buteo jamaicensis) and
Northern Harrier (Circus cyaneus), and the vulnerability of a frequent prey
species of those predators, Northern Bobwhite (Colinus virginianus). We mapped
occurrences of the raptors and kill locations of Northern Bobwhite to examine
spatial vulnerability patterns in relation to landscape complexity. We use an
offset model to examine spatially explicit habitat use patterns of these
predators in the Southern Great Plains of the United States, and monitored
vulnerability patterns of their prey species based on kill locations collected
during radio telemetry monitoring. Both predator density and predation-specific
mortality of Northern Bobwhite increased with vegetation complexity generated by
fine-scale interspersion of grassland and woodland. Predation pressure was lower
in more homogeneous landscapes where overlap of the two predators was less
frequent. Predator overlap created areas of high risk for Northern Bobwhite
amounting to 32% of the land area where landscape complexity was high and 7%
where complexity was lower. Our study emphasizes the need to evaluate the role of
landscape structure on predation dynamics and reveals another threat from woody
encroachment in grasslands.
PMID- 28690808
TI - Transcriptome predictors of coral survival and growth in a highly variable
environment.
AB - Concern over rapid environmental shifts associated with climate change has led to
a search for molecular markers of environmental tolerance. Climate-associated
gene expression profiles exist for a number of systems, but have rarely been tied
to fitness outcomes, especially in nonmodel organisms. We reciprocally
transplanted corals between two backreef locations with more and less variable
temperature regimes to disentangle effects of recent and native environment on
survival and growth. Coral growth over 12 months was largely determined by local
environment. Survival, however, was impacted by native environment; corals from
the more variable environment had 22% higher survivorship. By contrast, corals
native to the less variable environment had more variable survival. This might
represent a "selective sieve" where poor survivors are filtered from the more
stressful environment. We also find a potential fitness trade-off-corals with
high survival under stressful conditions grew less in the more benign
environment. Transcriptome samples taken a year before transplantation were used
to examine gene expression patterns that predicted transplant survival and
growth. Two separate clusters of coexpressed genes were predictive of survival in
the two locations. Genes from these clusters are candidate biomarkers for
predicting persistence of corals under future climate change scenarios.
PMID- 28690809
TI - Infochemical use and dietary specialization in parasitoids: a meta-analysis.
AB - Many parasitoid species use olfactory cues to locate their hosts. In tritrophic
systems, parasitoids of herbivores can exploit the chemical blends emitted by
plants in reaction to herbivore-induced damage, known as herbivore-induced plant
volatiles (HIPVs). In this study, we explored the specificity and innateness of
parasitoid responses to HIPVs using a meta-analysis of data from the literature.
Based on the concept of dietary specialization and infochemical use, we
hypothesized that (i) specialist parasitoids (i.e., with narrow host ranges)
should be attracted to specific HIPV signals, whereas generalist parasitoids
(i.e., with broad host ranges) should be attracted to more generic HIPV signals
and (ii) specialist parasitoids should innately respond to HIPVs, whereas
generalist parasitoids should have to learn to associate HIPVs with host
presence. We characterized the responses of 66 parasitoid species based on
published studies of parasitoid behavior. Our meta-analysis showed that (i) as
predicted, specialist parasitoids were attracted to more specific signals than
were generalist parasitoids but, (ii) contrary to expectations, response
innateness depended on a parasitoid's target host life stage rather than on its
degree of host specialization: parasitoids of larvae were more likely to show an
innate response to HIPVs than were parasitoids of adults. This result changes our
understanding of dietary specialization and highlights the need for further
theoretical research that will help clarify infochemical use by parasitoids.
PMID- 28690810
TI - Improving inference for aerial surveys of bears: The importance of assumptions
and the cost of unnecessary complexity.
AB - Obtaining useful estimates of wildlife abundance or density requires thoughtful
attention to potential sources of bias and precision, and it is widely understood
that addressing incomplete detection is critical to appropriate inference. When
the underlying assumptions of sampling approaches are violated, both increased
bias and reduced precision of the population estimator may result. Bear (Ursus
spp.) populations can be difficult to sample and are often monitored using mark
recapture distance sampling (MRDS) methods, although obtaining adequate sample
sizes can be cost prohibitive. With the goal of improving inference, we examined
the underlying methodological assumptions and estimator efficiency of three
datasets collected under an MRDS protocol designed specifically for bears. We
analyzed these data using MRDS, conventional distance sampling (CDS), and open
distance sampling approaches to evaluate the apparent bias-precision tradeoff
relative to the assumptions inherent under each approach. We also evaluated the
incorporation of informative priors on detection parameters within a Bayesian
context. We found that the CDS estimator had low apparent bias and was more
efficient than the more complex MRDS estimator. When combined with informative
priors on the detection process, precision was increased by >50% compared to the
MRDS approach with little apparent bias. In addition, open-distance sampling
models revealed a serious violation of the assumption that all bears were
available to be sampled. Inference is directly related to the underlying
assumptions of the survey design and the analytical tools employed. We show that
for aerial surveys of bears, avoidance of unnecessary model complexity, use of
prior information, and the application of open population models can be used to
greatly improve estimator performance and simplify field protocols. Although we
focused on distance sampling-based aerial surveys for bears, the general concepts
we addressed apply to a variety of wildlife survey contexts.
PMID- 28690811
TI - Local scale processes drive long-term change in biodiversity of sandy beach
ecosystems.
AB - Evaluating impacts to biodiversity requires ecologically informed comparisons
over sufficient time spans. The vulnerability of coastal ecosystems to
anthropogenic and climate change-related impacts makes them potentially valuable
indicators of biodiversity change. To evaluate multidecadal change in
biodiversity, we compared results from intertidal surveys of 13 sandy beaches
conducted in the 1970s and 2009-11 along 500 km of coast (California, USA). Using
a novel extrapolation approach to adjust species richness for sampling effort
allowed us to address data gaps and has promise for application to other data
limited biodiversity comparisons. Long-term changes in species richness varied in
direction and magnitude among beaches and with human impacts but showed no
regional patterns. Observed long-term changes in richness differed markedly among
functional groups of intertidal invertebrates. At the majority (77%) of beaches,
changes in richness were most evident for wrack-associated invertebrates
suggesting they have disproportionate vulnerability to impacts. Reduced diversity
of this group was consistent with long-term habitat loss from erosion and sea
level rise at one beach. Wrack-associated species richness declined over time at
impacted beaches (beach fill and grooming), despite observed increases in overall
intertidal richness. In contrast richness of these taxa increased at more than
half (53%) of the beaches including two beaches recovering from decades of off
road vehicle impacts. Over more than three decades, our results suggest that
local scale processes exerted a stronger influence on intertidal biodiversity on
beaches than regional processes and highlight the role of human impacts for local
spatial scales. Our results illustrate how comparisons of overall biodiversity
may mask ecologically important changes and stress the value of evaluating
biodiversity change in the context of functional groups. The long-term loss of
wrack-associated species, a key component of sandy beach ecosystems, documented
here represents a significant threat to the biodiversity and function of coastal
ecosystems.
PMID- 28690812
TI - Of beta diversity, variance, evenness, and dissimilarity.
AB - The amount of variation in species composition among sampling units or beta
diversity has become a primary tool for connecting the spatial structure of
species assemblages to ecological processes. Many different measures of beta
diversity have been developed. Among them, the total variance in the community
composition matrix has been proposed as a single-number estimate of beta
diversity. In this study, I first show that this measure summarizes the
compositional variation among sampling units after nonlinear transformation of
species abundances. Therefore, it is not always adequate for estimating beta
diversity. Next, I propose an alternative approach for calculating beta diversity
in which variance is substituted by a weighted measure of concentration (i.e., an
inverse measure of evenness). The relationship between this new measure of beta
diversity and so-called multiple-site dissimilarity measures is also discussed.
PMID- 28690813
TI - Bacterial phytopathogen infection disrupts belowground plant indirect defense
mediated by tritrophic cascade.
AB - Plants can defend themselves against herbivores through activation of defensive
pathways and attraction of third-trophic-level predators and parasites. Trophic
cascades that mediate interactions in the phytobiome are part of a larger dynamic
including the pathogens of the plant itself, which are known to greatly influence
plant defenses. As such, we investigated the impact of a phloem-limited bacterial
pathogen, Candidatus Liberibacter asiaticus (CLas), in cultivated citrus
rootstock on a well-studied belowground tritrophic interaction involving the
attraction of an entomopathogenic nematode (EPN), Steinernema diaprepesi, to
their root-feeding insect hosts, Diaprepes abbreviatus larvae. Using belowground
olfactometers, we show how CLas infection interferes with this belowground
interaction by similarly inducing the release of a C12 terpene, pregeijerene, and
disconnecting the association of the terpene with insect presence. D. abbreviatus
larvae that were not feeding but in the presence of a CLas-infected plant were
more likely to be infected by EPN than those near uninfected plants. Furthermore,
nonfeeding larvae associated with CLas-infected plants were just as likely to be
infected by EPN as those near noninfected plants with D. abbreviatus larval
damage. Larvae of two weevil species, D. abbreviatus and Pachnaeus litus, were
also more attracted to plants with infection than to uninfected plants. D.
abbreviatus larvae were most active when exposed to pregeijerene at a
concentration of 0.1 MUg/MUl. We attribute this attraction to CLas-infected
plants to the same signal previously thought to be a herbivore-induced plant
volatile specifically induced by root-feeding insects, pregeijerene, by assessing
volatiles collected from the roots of infected plants and uninfected plants with
and without feeding D. abbreviatus. Synthesis. Phytopathogens can influence the
structuring of soil communities extending to the third trophic level. Field
populations of EPN may be less effective at host-finding using pregeijerene as a
cue in citrus grove agroecosystems with high presence of CLas infection.
PMID- 28690814
TI - Barcoding rotifer biodiversity in Mediterranean ponds using diapausing egg banks.
AB - The biodiversity of Mediterranean freshwater bodies is among the most threatened
worldwide; therefore, its accurate estimation is an urgent issue. However,
traditional methods are likely to underestimate freshwater zooplankton
biodiversity due to its high species seasonality and cryptic diversity. We test
the value of applying DNA barcoding to diapausing egg banks, in combination with
the creation of a reference collection of DNA barcodes using adult individual
samples, to characterize rotifer communities. We use monogonont rotifers from two
lakes in Donana National Park and one from Ruidera Natural Park in Spain as
models to create a reference collection of DNA barcodes for taxonomically
diagnosed adult individuals sampled from the water column, to compare with the
sequences obtained from individual eggs from the diapausing egg banks. We apply
two different approaches to carry out DNA taxonomy analyses, the generalized
mixed Yule coalescent method (GMYC) and the Automatic Barcode Gap Discovery
(ABGD), to the obtained sequences and to publicly available rotifer sequences. We
obtained a total of 210 new rotifer COI sequences from all three locations (151
diapausing eggs and 59 adults). Both GMYC and ABGD generated the same 35
operational taxonomic units (OTUs), revealing four potential cryptic species.
Most sequences obtained from diapausing eggs (85%) clustered with sequences
obtained from morphologically diagnosed adults. Our approach, based on a single
sediment sample, retrieved estimates of rotifer biodiversity higher than or
similar to those of previous studies based on a number of seasonal samples. This
study shows that DNA barcoding of diapausing egg banks is an effective aid to
characterize rotifer diversity in Mediterranean freshwater bodies.
PMID- 28690815
TI - How weather instead of urbanity measures affects song trait variability in three
European passerine bird species.
AB - Previous studies detected an influence of urban characteristics on song traits in
passerine birds, that is, song adjustments to ambient noise in urban areas.
Several studies already described the effect of weather conditions on the
behavior of birds, but not the effect on song traits. We investigate, if song
trait variability changes along a continuous urbanity gradient in Frankfurt am
Main, Germany. We examined, for the first time on a larger scale, the influence
of weather on song parameters. We made song recordings of three common passerine
species: the blue and great tit (Cyanistes caeruleus (Linnaeus, 1758) and Parus
major Linnaeus, 1758) and the European blackbird (Turdus merula Linnaeus, 1758).
We measured different song traits and performed statistical analyses and modeling
on a variety of variables-among them urbanity and weather parameters. Remarkably,
we found only few cases of a significant influence of urbanity parameters on song
traits. The influence of weather parameters (air pressure, atmospheric humidity,
air and soil temperatures) on song traits was highly significant. Birds in
Frankfurt face high noise pollution and might show different adaptations to high
noise levels. The song trait variability of the investigated species is affected
more by weather conditions than by urban characteristics in Frankfurt. However,
the three species react differently to specific weather parameters. Smaller
species seem to be more affected by weather than larger species.
PMID- 28690816
TI - Past, current, and future trends of red spiny lobster based on PCA with MaxEnt
model in Galapagos Islands, Ecuador.
AB - In order to enhance in terms of accuracy and predict the modeling of the
potential distribution of species, the integration of using principal components
of environmental variables as input of maximum entropy (MaxEnt) has been proposed
in this study. Principal components selected previously from the principal
component analysis results performed in ArcGIS in the environmental variables was
used as an input data of MaxEnt instead of raw data to model the potential
distribution of red spiny lobster from the year 1997 to 2015 and for three
different future scenarios 2020, 2050, and 2070. One set of six original
environmental variables pertaining to the years 1997-2015 and one set of four
variables for future scenarios were transformed independently into a single
multiband raster in ArcGIS in order to select the variables whose eigenvalues
explains more than 5% of the total variance with the purpose to use in the
modeling prediction in MaxEnt. The years 1997 and 1998 were chosen to compare the
accuracy of the model, showing better results using principal components instead
of raw data in terms of area under the curve and partial receiver operating
characteristic as well as better predictions of suitable areas. Using principal
components as input of MaxEnt enhances the prediction of good habitat suitability
for red spiny lobster; however, future scenarios suggest an adequate management
by researches to elaborate appropriate guidelines for the conservation of the
habitat for this valuable specie with face to the climate change.
PMID- 28690817
TI - "How" and "what" matters: Sampling method affects biodiversity estimates of reef
fishes.
AB - Understanding changes in biodiversity requires the implementation of monitoring
programs encompassing different dimensions of biodiversity through varying
sampling techniques. In this work, fish assemblages associated with the "outer"
and "inner" sides of four marinas, two at the Canary Islands and two at southern
Portugal, were investigated using three complementary sampling techniques:
underwater visual censuses (UVCs), baited cameras (BCs), and fish traps (FTs). We
firstly investigated the complementarity of these sampling methods to describe
species composition. Then, we investigated differences in taxonomic (TD),
phylogenetic (PD) and functional diversity (FD) between sides of the marinas
according to each sampling method. Finally, we explored the
applicability/reproducibility of each sampling technique to characterize fish
assemblages according to these metrics of diversity. UVCs and BCs provided
complementary information, in terms of the number and abundances of species,
while FTs sampled a particular assemblage. Patterns of TD, PD, and FD between
sides of the marinas varied depending on the sampling method. UVC was the most
cost-efficient technique, in terms of personnel hours, and it is recommended for
local studies. However, for large-scale studies, BCs are recommended, as it
covers greater spatio-temporal scales by a lower cost. Our study highlights the
need to implement complementary sampling techniques to monitor ecological change,
at various dimensions of biodiversity. The results presented here will be useful
for optimizing future monitoring programs.
PMID- 28690818
TI - Combining field experiments and predictive models to assess potential for
increased plant diversity to climate-proof intensive agriculture.
AB - Agricultural production systems face increasing threats from more frequent and
extreme weather fluctuations associated with global climate change. While there
is mounting evidence that increased plant community diversity can reduce the
variability of ecosystem functions (such as primary productivity) in the face of
environmental fluctuation, there has been little work testing whether this is
true for intensively managed agricultural systems. Using statistical modeling
techniques to fit environment-productivity relationships offers an efficient
means of leveraging hard-won experimental data to compare the potential
variability of different mixtures across a wide range of environmental contexts.
We used data from two multiyear field experiments to fit climate-soil
productivity models for two pasture mixtures under intensive grazing-one composed
of two drought-sensitive species (standard), and an eight-species mixture
including several drought-resistant species (complex). We then used these models
to undertake a scoping study estimating the mean and coefficient of variation
(CV) of annual productivity for long-term climate data covering all New Zealand
on soils with low, medium, or high water-holding capacity. Our results suggest
that the complex mixture is likely to have consistently lower CV in productivity,
irrespective of soil type or climate regime. Predicted differences in mean annual
productivity between mixtures were strongly influenced by soil type and were
closely linked to mean annual soil water availability across all soil types.
Differences in the CV of productivity were only strongly related to interannual
variance in water availability for the lowest water-holding capacity soil. Our
results show that there is considerable scope for mixtures including drought
tolerant species to enhance certainty in intensive pastoral systems. This
provides justification for investing resources in a large-scale distributed
experiment involving many sites under different environmental contexts to confirm
these findings.
PMID- 28690819
TI - Molecular genetic analysis of two native desert palm genera, Washingtonia and
Brahea, from the Baja California Peninsula and Guadalupe Island.
AB - The complex geological and ecological processes that have generated high levels
of biodiversity and endemism in the Baja California Peninsula have been the
subject of intensive study. However, relatively little is known about
phylogeography of the iconic endemic palm species of this region. We therefore
analyzed a total of 2,294 bp of chloroplast and 738 bp of nuclear sequence data
in 169 samples of five native palm species from Baja California, Sonora and
Guadalupe Island. We found that Washingtonia and Brahea palms had low levels of
genetic diversity and were highly structured, with the majority of species and
major geographic regions being characterized by distinct haplotypes. We also
found strong support for currently recognized species in Washingtonia, but our
results were less clear cut for Brahea due to haplotype sharing. Furthermore,
patterns of population structure were broadly consistent with historical
vicariant events such as the inundation of the Isthmus of La Paz, the formation
of the Sea of Cortez, and the more recent colonization and isolation of Guadalupe
Island's palms. Our findings contribute toward a growing appreciation of the
complexity of plant responses to past geological changes and also provide
valuable baseline genetic data on relict American palm species.
PMID- 28690820
TI - Giant invasive Heracleum persicum: Friend or foe of plant diversity?
AB - The impact of invasion on diversity varies widely and remains elusive. Despite
the considerable attempts to understand mechanisms of biological invasion, it is
largely unknown whether some communities' characteristics promote biological
invasion, or whether some inherent characteristics of invaders enable them to
invade other communities. Our aims were to assess the impact of one of the
massive plant invaders of Scandinavia on vascular plant species diversity,
disentangle attributes of invasible and noninvasible communities, and evaluate
the relationship between invasibility and genetic diversity of a dominant
invader. We studied 56 pairs of Heracleum persicum Desf. ex Fisch.-invaded and
noninvaded plots from 12 locations in northern Norway. There was lower native
cover, evenness, taxonomic diversity, native biomass, and species richness in the
invaded plots than in the noninvaded plots. The invaded plots had nearly two
native species fewer than the noninvaded plots on average. Within the invaded
plots, cover of H. persicum had a strong negative effect on the native cover,
evenness, and native biomass, and a positive association with the height of the
native plants. Plant communities containing only native species appeared more
invasible than those that included exotic species, particularly H. persicum.
Genetic diversity of H. persicum was positively correlated with invasibility but
not with community diversity. The invasion of a plant community by H. persicum
exerts consistent negative pressure on vascular plant diversity. The lack of
positive correlation between impacts and genetic diversity of H. persicum
indicates that even a small founder population may cause high impact. We
highlight community stability or saturation as an important determinant of
invasibility. While the invasion by H. persicum may decrease susceptibility of a
plant community to further invasion, it severely reduces the abundance of native
species and makes them more vulnerable to competitive exclusion.
PMID- 28690821
TI - The mitochondrial genome of a sea anemone Bolocera sp. exhibits novel genetic
structures potentially involved in adaptation to the deep-sea environment.
AB - The deep sea is one of the most extensive ecosystems on earth. Organisms living
there survive in an extremely harsh environment, and their mitochondrial energy
metabolism might be a result of evolution. As one of the most important
organelles, mitochondria generate energy through energy metabolism and play an
important role in almost all biological activities. In this study, the mitogenome
of a deep-sea sea anemone (Bolocera sp.) was sequenced and characterized. Like
other metazoans, it contained 13 energy pathway protein-coding genes and two
ribosomal RNAs. However, it also exhibited some unique features: just two
transfer RNA genes, two group I introns, two transposon-like noncanonical open
reading frames (ORFs), and a control region-like (CR-like) element. All of the
mitochondrial genes were coded by the same strand (the H-strand). The genetic
order and orientation were identical to those of most sequenced actiniarians.
Phylogenetic analyses showed that this species was closely related to Bolocera
tuediae. Positive selection analysis showed that three residues (31 L and 42 N in
ATP6, 570 S in ND5) of Bolocera sp. were positively selected sites. By comparing
these features with those of shallow sea anemone species, we deduced that these
novel gene features may influence the activity of mitochondrial genes. This study
may provide some clues regarding the adaptation of Bolocera sp. to the deep-sea
environment.
PMID- 28690822
TI - Genetic differences between wild and hatchery-bred brown trout (Salmo trutta L.)
in single nucleotide polymorphisms linked to selective traits.
AB - To study effects from natural selection acting on brown trout in a natural stream
habitat compared with a hatchery environment, 3,781 single nucleotide
polymorphism (SNP) markers were analyzed in three closely related groups of brown
trout (Salmo trutta L.). Autumn (W/0+, n = 48) and consecutive spring (W/1+, n =
47) samples of brown trout individuals belonging to the same cohort and stream
were retrieved using electrofishing. A third group (H/1+, n = 48) comprised
hatchery-reared individuals, bred from a mixture of wild parents of the strain of
the two former groups and from a neighboring stream. Pairwise analysis of FST
outliers and analysis under a hierarchical model by means of ARLEQUIN software
detected 421 (10.8%) candidates of selection, before multitest correction.
BAYESCAN software detected 10 candidate loci, all of which were included among
the ARLEQUIN candidate loci. Body length was significantly different across
genotypes at 10 candidate loci in the W/0+, at 34 candidate loci in the W/1+ and
at 21 candidate loci in the H/1+ group. The W/1+ sample was tested for genotype
specific body length at all loci, and significant differences were found in 10.6%
of all loci, and of these, 14.2% had higher frequency of the largest genotype in
the W/1+ sample than in W/0+. The corresponding proportion among the candidate
loci of W/1+ was 22.7% with genotype-specific body length, and 88.2% of these had
increased frequency of the largest genotype from W/0+ to W/1+, indicating a
linkage between these loci and traits affecting growth and survival under this
stream's environmental conditions. Bayesian structuring of all loci, and of the
noncandidate loci suggested two (K = 2), alternatively four clusters (K = 4).
This differed from the candidate SNPs, which suggested only two clusters. In both
cases, the hatchery fish dominated one cluster, and body length of W/1+ fish was
positively correlated with membership of one cluster both from the K = 2 and the
K = 4 structure. Our analysis demonstrates profound genetic differentiation that
can be linked to differential selection on a fitness-related trait (individual
growth) in brown trout living under natural vs. hatchery conditions. Candidate
SNP loci linked to genes affecting individual growth were identified and provide
important inputs into future mapping of the genetic basis of brown trout body
size selection.
PMID- 28690823
TI - Opposing effects of mortality factors on progeny operational sex ratio may thwart
adaptive manipulation of primary sex ratio.
AB - Despite extensive research on mechanisms generating biases in sex ratios, the
capacity of natural enemies to shift or further skew operational sex ratios
following sex allocation and parental care remains largely unstudied in natural
populations. Male cocoons of the sawfly Neodiprion abietis (Hymenoptera:
Diprionidae) are consistently smaller than those of females, with very little
overlap, and thus, we were able to use cocoon size to sex cocoons. We studied
three consecutive cohorts of N. abietis in six forest stands to detect cocoon
volume-associated biases in the attack of predators, pathogens, and parasitoids
and examine how the combined effect of natural enemies shapes the realized
operational sex ratio. Neodiprion abietis mortality during the cocoon stage was
sex-biased, being 1.6 times greater for males than females. Greater net mortality
in males occurred because male-biased mortality caused by a pteromalid parasitic
wasp and a baculovirus was greater and more skewed than female-biased mortality
caused by ichneumonid parasitic wasps. Variation in the susceptibility of each
sex to each family of parasitoids was associated with differences in size and
life histories of male and female hosts. A simulation based on the data indicated
that shifts in the nature of differential mortality have different effects on the
sex ratio and fitness of survivors. Because previous work has indicated that
reduced host plant foliage quality induces female-biased mortality in this
species, bottom-up and top-down factors acting on populations can affect
operational sex ratios in similar or opposite ways. Shifts in ecological
conditions therefore have the potential to alter progeny fitness and produce
extreme sex ratio skews, even in the absence of unbalanced sex allocation. This
would limit the capacity of females to anticipate the operational sex ratio and
reliably predict the reproductive success of each gender at sex allocation.
PMID- 28690824
TI - High invasion potential of Hydrilla verticillata in the Americas predicted using
ecological niche modeling combined with genetic data.
AB - Ecological niche modeling is an effective tool to characterize the spatial
distribution of suitable areas for species, and it is especially useful for
predicting the potential distribution of invasive species. The widespread
submerged plant Hydrilla verticillata (hydrilla) has an obvious phylogeographical
pattern: Four genetic lineages occupy distinct regions in native range, and only
one lineage invades the Americas. Here, we aimed to evaluate climatic niche
conservatism of hydrilla in North America at the intraspecific level and explore
its invasion potential in the Americas by comparing climatic niches in a
phylogenetic context. Niche shift was found in the invasion process of hydrilla
in North America, which is probably mainly attributed to high levels of somatic
mutation. Dramatic changes in range expansion in the Americas were predicted in
the situation of all four genetic lineages invading the Americas or future
climatic changes, especially in South America; this suggests that there is a high
invasion potential of hydrilla in the Americas. Our findings provide useful
information for the management of hydrilla in the Americas and give an example of
exploring intraspecific climatic niche to better understand species invasion.
PMID- 28690825
TI - White-crowned sparrow males show immediate flexibility in song amplitude but not
in song minimum frequency in response to changes in noise levels in the field.
AB - The soundscape acts as a selective agent on organisms that use acoustic signals
to communicate. A number of studies document variation in structure, amplitude,
or timing of signal production in correspondence with environmental noise levels
thus supporting the hypothesis that organisms are changing their signaling
behaviors to avoid masking. The time scale at which organisms respond is of
particular interest. Signal structure may evolve across generations through
processes such as cultural or genetic transmission. Individuals may also change
their behavior during development (ontogenetic change) or in real time (i.e.,
immediate flexibility). These are not mutually exclusive mechanisms, and all must
be investigated to understand how organisms respond to selection pressures from
the soundscape. Previous work on white-crowned sparrows (Zonotrichia leucophrys)
found that males holding territories in louder areas tend to sing higher
frequency songs and that both noise levels and song frequency have increased over
time (30 years) in urban areas. These previous findings suggest that songs are
changing across generations; however, it is not known if this species also
exhibits immediate flexibility. Here, we conducted an exploratory, observational
study to ask whether males change the minimum frequency of their song in response
to immediate changes in noise levels. We also ask whether males sing louder, as
increased minimum frequency may be physiologically linked to producing sound at
higher amplitudes, in response to immediate changes in environmental noise. We
found that territorial males adjust song amplitude but not minimum frequency in
response to changes in environmental noise levels. Our results suggest that males
do not show immediate flexibility in song minimum frequency, although
experimental manipulations are needed to test this hypothesis further. Our work
highlights the need to investigate multiple mechanisms of adaptive response to
soundscapes.
PMID- 28690826
TI - Demographics, reproduction, growth, and abundance of Jollyville Plateau
salamanders (Eurycea tonkawae).
AB - Insights into the ecology and natural history of the neotenic salamander, Eurycea
tonkawae, are provided from eight years of capture-recapture data from 10,041
captures of 7,315 individuals at 16 sites. Eurycea tonkawae exhibits seasonal
reproduction, with peak gravidity occurring in the fall and winter. Size
frequency data indicated recruitment occurred in the spring and summer. Open
population capture-recapture models revealed a similar seasonal pattern at two of
three sites, while recruitment was dependent on flow at the third site. Females
can reach sexual maturity within one year, and oviposition likely takes place
below ground. The asymptotic body length of 1,290 individuals was estimated as
31.73 mm (at ca. two years of age), although there was substantial heterogeneity
among growth trajectories. Longevity was approximately eight years, and the
median age for a recaptured adult was 2.3 years. Abundance estimated from closed
population and robust-design capture-recapture models varied widely within and
among sites (range 41-834), although, surprisingly, dramatic changes in abundance
were not observed following prolonged dry periods. Seasonal migration patterns of
second-year and older adults may help explain lower ratios of large individuals
and higher temporary emigration during the latter half of the year, but further
study is required. Low numbers of captures and recaptures precluded the use of
open-population models to estimate demographic parameters at several sites;
therefore, closed-population (or robust-design) methods are generally
recommended. Based on observations of their life history and population
demographics, E. tonkawae seems well adapted to conditions where spring flow is
variable and surface habitat periodically goes dry.
PMID- 28690827
TI - Stabilizing mechanisms in a food web with an introduced omnivore.
AB - Intraguild predation (IGP) is an omnivorous food web configuration in which the
top predator consumes both a competitor (consumer) and a second prey that it
shares with the competitor. This omnivorous configuration occurs frequently in
food webs, but theory suggests that it is unstable unless stabilizing mechanisms
exist that can decrease the strength of the omnivore and consumer interaction.
Although these mechanisms have been documented in native food webs, little is
known about whether they operate in the context of an introduced species. Here,
we study a marine mussel aquaculture system where the introduction of omnivorous
mussels should generate an unstable food web that favors the extinction of the
consumer, yet it persists. Using field and laboratory approaches, we searched for
stabilizing mechanisms that could reduce interaction strengths in the food web.
While field zooplankton counts suggested that mussels influence the composition
and abundance of copepods, stable isotope results indicated that life-history
omnivory and cannibalism facilitated the availability of prey refugia, and
reduced competition and the interaction strength between the mussel omnivore and
zooplankton consumers. In laboratory experiments, however, we found no evidence
of adaptive feeding which could weaken predator-consumer interactions. Our food
web study suggests that the impact of an introduced omnivore may not only depend
on its interaction with native species but also on the availability of
stabilizing mechanisms that alter the strength of those interactions.
PMID- 28690828
TI - Culture and identification of Borrelia spirochetes in human vaginal and seminal
secretions.
AB - Background: Recent reports indicate that more than 300,000 cases of Lyme disease
are diagnosed yearly in the USA. Preliminary clinical, epidemiological and
immunological studies suggest that infection with the Lyme disease spirochete
Borrelia burgdorferi (Bb) could be transferred from person to person via intimate
human contact without a tick vector. Detecting viable Borrelia spirochetes in
vaginal and seminal secretions would provide evidence to support this hypothesis.
Methods: Patients with and without a history of Lyme disease were selected for
the study after informed consent was obtained. Serological testing for Bb was
performed on all subjects. Semen or vaginal secretions were inoculated into BSK-H
medium and cultured for four weeks. Examination of genital cultures and culture
concentrates for the presence of spirochetes was performed using light and
darkfield microscopy, and spirochete concentrates were subjected to Dieterle
silver staining, anti-Bb immunohistochemical staining, molecular hybridization
and PCR analysis for further characterization. Immunohistochemical and molecular
testing was performed in three independent laboratories. Positive and negative
controls were included in all experiments. Results: Control subjects who were
asymptomatic and seronegative for Bb had no detectable spirochetes in genital
secretions by PCR analysis. In contrast, spirochetes were observed in cultures of
genital secretions from 11 of 13 subjects diagnosed with Lyme disease, and motile
spirochetes were detected in genital culture concentrates from 12 of 13 Lyme
disease patients using light and darkfield microscopy. Morphological features of
spirochetes were confirmed by Dieterle silver staining and immunohistochemical
staining of culture concentrates. Molecular hybridization and PCR testing
confirmed that the spirochetes isolated from semen and vaginal secretions were
strains of Borrelia, and all cultures were negative for treponemal spirochetes.
PCR sequencing of cultured spirochetes from three couples having unprotected sex
indicated that two couples had identical strains of Bb sensu stricto in their
semen and vaginal secretions, while the third couple had identical strains of B.
hermsii detected in their genital secretions. Conclusions: The culture of viable
Borrelia spirochetes in genital secretions suggests that Lyme disease could be
transmitted by intimate contact from person to person.
PMID- 28690829
TI - A simple mathematical approach to the analysis of polypharmacology and
polyspecificity data.
AB - There many possible types of drug-target interactions, because there are a
surprising number of ways in which drugs and their targets can associate with one
another. These relationships are expressed as polypharmacology and
polyspecificity. Polypharmacology is the capability of a given drug to exhibit
activity with respect to multiple drug targets, which are not necessarily in the
same activity class. Adverse drug reactions ('side effects') are its principal
manifestation, but polypharmacology is also playing a role in the repositioning
of existing drugs for new therapeutic indications. Polyspecificity, on the other
hand, is the capability of a given target to exhibit activity with respect to
multiple, structurally dissimilar drugs. That these concepts are closely related
to one another is, surprisingly, not well known. It will be shown in this work
that they are, in fact, mathematically related to one another and are in essence
'two sides of the same coin'. Hence, information on polypharmacology provides
equivalent information on polyspecificity, and vice versa. Networks are playing
an increasingly important role in biological research. Drug-target networks, in
particular, are made up of drug nodes that are linked to specific target nodes if
a given drug is active with respect to that target. Such networks provide a
graphic depiction of polypharmacology and polyspecificity. However, by their
very nature they can obscure information that may be useful in their
interpretation and analysis. This work will show how such latent information can
be used to determine bounds for the degrees of polypharmacology and
polyspecificity, and how to estimate other useful features associated with the
lack of completeness of most drug-target datasets.
PMID- 28690830
TI - In silico discovery of terpenoid metabolism in Cannabis sativa.
AB - Due to their efficacy, cannabis based therapies are currently being prescribed
for the treatment of many different medical conditions. Interestingly, treatments
based on the use of cannabis flowers or their derivatives have been shown to be
very effective, while therapies based on drugs containing THC alone lack
therapeutic value and lead to increased side effects, likely resulting from the
absence of other pivotal entourage compounds found in the Phyto-complex. Among
these compounds are terpenoids, which are not produced exclusively by cannabis
plants, so other plant species must share many of the enzymes involved in their
metabolism. In the present work, 23,630 transcripts from the canSat3 reference
transcriptome were scanned for evolutionarily conserved protein domains and
annotated in accordance with their predicted molecular functions. A total of 215
evolutionarily conserved genes encoding enzymes presumably involved in terpenoid
metabolism are described, together with their expression profiles in different
cannabis plant tissues at different developmental stages. The resource presented
here will aid future investigations on terpenoid metabolism in Cannabis sativa.
PMID- 28690831
TI - Patient waiting time in the outpatient clinic at a central surgical hospital of
Vietnam: Implications for resource allocation.
AB - Background: Patient waiting time is considered as a crucial parameter in the
assessment of healthcare quality and patients' satisfaction towards healthcare
services. Data concerning this has remained limited in Vietnam. Thus, this study
aims to assess patient waiting time in the outpatient clinic in Viet Duc Hospital
(Hanoi, Vietnam) in order to enable stakeholders to inform evidence-based
interventions to improve the quality of healthcare services. Methods: A cross
sectional study was conducted from June 2014 to June 2015 in the outpatient
clinic at Viet Duc Hospital. Waiting time stratified by years (2014 and 2015),
months of the year, weekdays, and hours of the day were extracted from Hospital
Management software and carefully calculated. Stata 12.0 was employed to analyze
data, including the average time (M+/- SD), frequencies and percentage (%).
Results: There was a total of 137,881 patients involved in the study. The average
waiting time from registration to preliminary diagnosis in 2014 was 50.41
minutes, and in 2015 was 42.05 minutes. A longer waiting time was recorded in the
morning and in those having health insurance. Conclusions: Our study highlights
the essential need for human resource promotion to reduce patient waiting time.
Also, attention should be paid to the simplification of administrative procedures
in order to reduce waiting time among insured patients.
PMID- 28690832
TI - Validation of commercial ERK antibodies against the ERK orthologue of the
scleractinian coral Stylophora pistillata.
AB - The extracellular signal-regulated protein kinase (ERK) signalling pathway
controls key cellular processes, such as cell cycle regulation, cell fate
determination and the response to external stressors. Although ERK functions are
well studied in a variety of living organisms ranging from yeast to mammals, its
functions in corals are still poorly known. The present work aims to give
practical tools to study the expression level of ERK protein and the activity of
the ERK signalling pathway in corals. The antibody characterisation experiment
was performed five times and identical results were obtained. The present study
validated the immune-reactivity of commercially available antibodies directed
against ERK and its phosphorylated/activated forms on protein extracts of the
reef-building coral Stylophora pistillata.
PMID- 28690833
TI - Effect of PVP on the characteristic of modified membranes made from waste PET
bottles for humic acid removal.
AB - Background: The aim of the present study was to evaluate the possibility of using
recycled polymer (waste polyethylene terephthalate [PET] bottles) as a membrane
material. Furthermore, the effect of the addition of a pore-forming agent and
preparation conditions was also observed. Methods: Porous polymeric membranes
were prepared via thermally induced phase separation by dissolving recycled PET
in phenol. PET polymer was obtained from waste plastic bottles as a new source of
polymeric material. For original PET membrane, the casting solution was prepared
by dissolving of 20wt% PET in phenol solution. For PET modified membrane, a 5 wt%
of polyvinylpyrrolidone (PVP) was added into polymer solution. The solution was
cast onto a glass plate at room temperature followed by evaporation before the
solidification process. The membranes formed were characterized in terms of
morphology, chemical group, and filtration performance. A humic acid solution was
used to identify the permeability and the solute rejection of the membranes.
Results: The results showed that the recycled PET from waste plastic bottles was
applicable to use as a membrane material for a water treatment process. The
highest rejection of humic acid in a water sample, which reached up to 75.92%,
was obtained using the PET/PVP membrane. Conclusions: The recycled PET from waste
bottles was successfully used to prepare porous membrane. The membrane was
modified by the addition of PVP as a membrane modifying agent. SEM analysis
confirmed that the original PET membrane has a rough and large pore structure.
The addition of PVP improved the pore density with a narrow pore structure. The
PET/PVP membrane conditioned with evaporation was the best in humic acid
rejection.
PMID- 28690834
TI - From disease modelling to personalised therapy in patients with CEP290 mutations.
AB - Mutations that give rise to premature termination codons are a common cause of
inherited genetic diseases. When transcripts containing these changes are
generated, they are usually rapidly removed by the cell through the process of
nonsense-mediated decay. Here we discuss observed changes in transcripts of the
centrosomal protein CEP290 resulting not from degradation, but from changes in
exon usage. We also comment on a landmark paper (Drivas et al. Sci Transl Med.
2015) where modelling this process of exon usage may be used to predict disease
severity in CEP290 ciliopathies, and how understanding this process may
potentially be used for therapeutic benefit in the future.
PMID- 28690835
TI - Dietary assessment methods in epidemiological research: current state of the art
and future prospects.
AB - Self-reported dietary intake is assessed by methods of real-time recording (food
diaries and the duplicate portion method) and methods of recall (dietary
histories, food frequency questionnaires, and 24-hour dietary recalls). Being
less labor intensive, recall methods are more frequently employed in nutritional
epidemiological investigations. However, sources of error, which include the
participants' inability to fully and accurately recall their intakes as well as
limitations inherent in the food composition databases applied to convert the
reported food consumption to energy and nutrient intakes, may limit the validity
of the generated information. The use of dietary biomarkers is often recommended
to overcome such errors and better capture intra-individual variability in
intake; nevertheless, it has its own challenges. To address measurement error
associated with dietary questionnaires, large epidemiological investigations
often integrate sub-studies for the validation and calibration of the
questionnaires and/or administer a combination of different assessment methods
(e.g. administration of different questionnaires and assessment of biomarker
levels). Recent advances in the omics field could enrich the list of reliable
nutrition biomarkers, whereas new approaches employing web-based and smart phone
applications could reduce respondent burden and, possibly, reporting bias. Novel
technologies are increasingly integrated with traditional methods, but some
sources of error still remain. In the analyses, food and nutrient intakes always
need to be adjusted for total daily energy intake to account for errors related
to reporting.
PMID- 28690836
TI - Noise-induced and age-related hearing loss: new perspectives and potential
therapies.
AB - The classic view of sensorineural hearing loss has been that the primary damage
targets are hair cells and that auditory nerve loss is typically secondary to
hair cell degeneration. Recent work has challenged that view. In noise-induced
hearing loss, exposures causing only reversible threshold shifts (and no hair
cell loss) nevertheless cause permanent loss of >50% of the synaptic connections
between hair cells and the auditory nerve. Similarly, in age-related hearing
loss, degeneration of cochlear synapses precedes both hair cell loss and
threshold elevation. This primary neural degeneration has remained a "hidden
hearing loss" for two reasons: 1) the neuronal cell bodies survive for years
despite loss of synaptic connection with hair cells, and 2) the degeneration is
selective for auditory nerve fibers with high thresholds. Although not required
for threshold detection when quiet, these high-threshold fibers are critical for
hearing in noisy environments. Research suggests that primary neural degeneration
is an important contributor to the perceptual handicap in sensorineural hearing
loss, and it may be key to the generation of tinnitus and other associated
perceptual anomalies. In cases where the hair cells survive, neurotrophin
therapies can elicit neurite outgrowth from surviving auditory neurons and re
establishment of their peripheral synapses; thus, treatments may be on the
horizon.
PMID- 28690837
TI - The application of remote ischemic conditioning in cardiac surgery.
AB - Perioperative myocardial ischemia and infarction are the leading causes of
morbidity and mortality following anesthesia and surgery. The discovery of
endogenous cardioprotective mechanisms has led to testing of new methods to
protect the human heart. These approaches have included ischemic pre
conditioning, per-conditioning, post-conditioning, and remote conditioning of the
myocardium. Pre-conditioning and per-conditioning include brief and repetitive
periods of sub-lethal ischemia before and during prolonged ischemia,
respectively; and post-conditioning is applied at the onset of reperfusion.
Remote ischemic conditioning involves transient, repetitive, non-lethal ischemia
and reperfusion in one organ or tissue (remote from the heart) that renders
myocardium more resistant to lethal ischemia/reperfusion injury. In healthy,
young hearts, many conditioning maneuvers can significantly increase the
resistance of the heart against ischemia/reperfusion injury. The large
multicenter clinical trials with ischemic remote conditioning have not been
proven successful in cardiac surgery thus far. The lack of clinical success is
due to underlying risk factors that interfere with remote ischemic conditioning
and the use of cardioprotective agents that have activated the endogenous
cardioprotective mechanisms prior to remote ischemic conditioning. Future
preclinical research using remote ischemic conditioning will need to be conducted
using comorbid models.
PMID- 28690838
TI - Recent advances in high-throughput approaches to dissect enhancer function.
AB - The regulation of gene transcription in higher eukaryotes is accomplished through
the involvement of transcription start site (TSS)-proximal (promoters) and
distal (enhancers) regulatory elements. It is now well acknowledged that enhancer
elements play an essential role during development and cell differentiation,
while genetic alterations in these elements are a major cause of human disease.
Many strategies have been developed to identify and characterize enhancers. Here,
we discuss recent advances in high-throughput approaches to assess enhancer
activity, from the well-established massively parallel reporter assays to the
recent clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9
based technologies. We highlight how these approaches contribute toward a better
understanding of enhancer function, eventually leading to the discovery of new
types of regulatory sequences, and how the alteration of enhancers can affect
transcriptional regulation.
PMID- 28690839
TI - Recent advances in understanding and managing cancer pain.
AB - Cancer pain remains a significant clinical problem worldwide. Causes of cancer
pain are multifactorial and complex and are likely to vary with an array of tumor
related and host-related factors and processes. Pathophysiology is poorly
understood; however, new laboratory research points to cross-talk between cancer
cells and host's immune and neural systems as an important potential mechanism
that may be broadly relevant to many cancer pain syndromes. Opioids remain the
most effective pharmaceuticals used in the treatment of cancer pain. However,
their role has been evolving due to emerging awareness of risks of chronic opioid
therapy. Despite extensive research efforts, no new class of analgesics has been
developed. However, many potential therapeutic targets that may lead to the
establishment of new pharmaceuticals have been identified in recent years. It is
also expected that the role of non-pharmacological modalities of treatment will
grow in prominence. Specifically, neuromodulation, a rapidly expanding field, may
play a major role in the treatment of neuropathic cancer pain provided that
further technological progress permits the development of non-invasive and
inexpensive neuromodulation techniques.
PMID- 28690840
TI - Making the clock tick: the transcriptional landscape of the plant circadian
clock.
AB - Circadian clocks are molecular timekeepers that synchronise internal
physiological processes with the external environment by integrating light and
temperature stimuli. As in other eukaryotic organisms, circadian rhythms in
plants are largely generated by an array of nuclear transcriptional regulators
and associated co-regulators that are arranged into a series of interconnected
molecular loops. These transcriptional regulators recruit chromatin-modifying
enzymes that adjust the structure of the nucleosome to promote or inhibit DNA
accessibility and thus guide transcription rates. In this review, we discuss the
recent advances made in understanding the architecture of the Arabidopsis
oscillator and the chromatin dynamics that regulate the generation of rhythmic
patterns of gene expression within the circadian clock.
PMID- 28690841
TI - New frontiers in the treatment of systemic juvenile idiopathic arthritis.
AB - Systemic juvenile idiopathic arthritis (sJIA) and its most significant
complication, macrophage activation syndrome (MAS), have traditionally been
treated with steroids and non-steroidal anti-inflammatory medications. However,
the introduction of biologic medications that inhibit specific cytokines, such
interleukins 1 and 6, has changed the treatment paradigm for sJIA patients. In
this review, we discuss the therapies currently used in the treatment of sJIA as
well as novel targets and approaches under consideration, including mesenchymal
stromal cell therapy and JAK inhibitors. We also discuss targeting cytokines that
have been implicated in MAS, such as interferon gamma and interleukin 18.
PMID- 28690842
TI - Chemical genetics and strigolactone perception.
AB - Strigolactones (SLs) are a collection of related small molecules that act as
hormones in plant growth and development. Intriguingly, SLs also act as
ecological communicators between plants and mycorrhizal fungi and between host
plants and a collection of parasitic plant species. In the case of mycorrhizal
fungi, SLs exude into the soil from host roots to attract fungal hyphae for a
beneficial interaction. In the case of parasitic plants, however, root-exuded SLs
cause dormant parasitic plant seeds to germinate, thereby allowing the resulting
seedling to infect the host and withdraw nutrients. Because a laboratory-friendly
model does not exist for parasitic plants, researchers are currently using
information gleaned from model plants like Arabidopsis in combination with the
chemical probes developed through chemical genetics to understand SL perception
of parasitic plants. This work first shows that understanding SL signaling is
useful in developing chemical probes that perturb SL perception. Second, it
indicates that the chemical space available to probe SL signaling in both model
and parasitic plants is sizeable. Because these parasitic pests represent a major
concern for food insecurity in the developing world, there is great need for
chemical approaches to uncover novel lead compounds that perturb parasitic plant
infections.
PMID- 28690843
TI - The role of PD-1 in regulation of macrophage apoptosis and its subversion by
Leishmania donovani.
AB - Programmed death-1 receptor (PD-1) expressed in many immune cells is known to
trigger T-cell exhaustion but the significance of macrophage-associated PD-1 in
relevance to macrophage apoptosis is not known. This study is aimed to delineate
whether PD-1 pathway has any role in eliciting macrophage apoptosis and, if so,
then how the intra-macrophage parasite, Leishmania donovani modulates PD-1
pathway for protecting its niche. Resting macrophages when treated with H2O2
showed increased PD-1 expression and apoptosis, which was further enhanced on PD
1 agonist treatment. The administration of either PD-1 receptor or PD-1 ligand
blocking antibodies reversed the process thus documenting the involvement of PD-1
in macrophage apoptosis. On the contrary, L. donovani-infected macrophages showed
decreased PD-1 expression concurrent with inhibition of apoptosis. The activation
of PD-1 pathway was found to negatively regulate the phosphorylation of pro
survival AKT, which was reversed during infection. Infection-induced PD-1
downregulation led to the activation of AKT resulting in phosphorylation and
subsequent inhibition of proapoptotic protein BAD. Strong association of SHP2 (a
SH2-containing ubiquitously expressed tyrosine-specific protein phosphatase) with
PD-1 along with AKT deactivation observed in H2O2-treated macrophages was
reversed by L. donovani infection. Kinetic analysis coupled with inhibitor-based
approach and knockdown experiments demonstrated that L. donovani infection
actively downregulated the PD-1 by deactivating NFATc1 as revealed by its reduced
nuclear translocation. The study thus elucidates the detailed mechanism of the
role of PD-1 in macrophage apoptosis and its negative modulation by Leishmania
for their intracellular survival.
PMID- 28690844
TI - PD1 functions by inhibiting CD28-mediated co-stimulation.
PMID- 28690845
TI - Diagnostic autoantibodies for autoimmune liver diseases.
AB - Autoimmune liver diseases are conditions of low prevalence that comprise the
triad of autoimmune hepatitis, primary biliary cholangitis (cirrhosis) and
primary sclerosing cholangitis and their poorly characterised overlapping
syndromes. Diagnostic autoantibodies are associated with autoimmune hepatitis and
primary biliary cholangitis but not with primary sclerosing cholangitis.
Autoantibodies are useful disease markers that facilitate early diagnosis of
autoimmune hepatitis and primary biliary cholangitis and allow for therapeutic
intervention to prevent progression to liver cirrhosis and associated
complications. Adult onset type 1 autoimmune hepatitis is associated with F-actin
reactive smooth muscle autoantibody, antinuclear autoantibody in 60% of patients,
and autoantibody to SLA/LP in 15-20%. Juvenile onset type 2 autoimmune hepatitis
is associated with LKM-1 and LC-1 autoantibodies. Primary biliary cholangitis is
associated with a mitochondria-associated autoantibody designated M2 in >90% of
patients and with disease-specific antinuclear autoantibodies in 50% that bind to
antigens in the nuclear core complex and in multiple nuclear dots. Autoantibodies
to the nuclear core complex target gp210, nucleoporin p62 and nuclear lamin B
receptor. Autoantibodies to multiple nuclear dots target Sp100 and PML antigens.
Liver autoantibodies in asymptomatic patients with normal liver function may
precede the subsequent development of overt autoimmune liver disease. For routine
diagnostic immunology laboratories, initial screening for liver autoantibodies by
immunofluorescence remains the method of choice with confirmation for reactivity
with their target antigen by enzyme-linked immunosorbent assay (ELISA) or line
blot when required.
PMID- 28690846
TI - Tracking the T-cell repertoire after adoptive therapy.
PMID- 28690847
TI - The circulating life of a memory T-follicular helper cell.
PMID- 28690848
TI - Corrigendum: A generalized quantitative antibody homeostasis model: antigen
saturation, natural antibodies and a quantitative antibody network.
AB - [This corrects the article DOI: 10.1038/cti.2016.90.].
PMID- 28690849
TI - Altered regulatory T-cell fractions and Helios expression in clinically isolated
syndrome: clues to the development of multiple sclerosis.
AB - Development of multiple sclerosis (MS) is frequently preceded by an acute or
subacute neurological disturbance referred to as clinically isolated syndrome
(CIS). The specific immunological disturbances present in CIS remain
underexamined. This study analysed peripheral blood mononuclear cells from n=18
treatment-naive individuals with recently diagnosed CIS (<120 days) for
disturbances in the phenotype of T regulatory (Treg), follicular T regulatory
(Tfr), T helper (Th), follicular T helper (Tfh) and B cells. Relative to healthy
controls (n=19), CIS was associated with lower proportions of suppressive
CD45RA+FoxP3lo Treg and Tfr cells and greater proportions of non-suppressive
CD45RA-FoxP3lo and Th17-like Treg and Tfr. Lower Helios expression (maen
fluorescent intensity) was measured across all Treg and Tfr fractions in the CIS
group, suggesting less potent regulatory function. Greater frequencies of
activated, efficient B-cell helper Tfh subsets and a trend for a higher
proportion of IgD-CD27- B cells was also detected in the CIS group,
characteristics that were positively correlated with Treg and Tfr Helios
expression. These results indicate that Treg and Tfr impairment is an early
feature in MS.
PMID- 28690850
TI - Agammaglobulinaemia despite terminal B-cell differentiation in a patient with a
novel LRBA mutation.
AB - Mutations in lipopolysaccharide-responsive vesicle trafficking, beach and anchor
containing protein (LRBA) cause immune deficiency and inflammation. Here, we are
reporting a novel homozygous mutation in LRBA allele in 7-year-old Omani boy,
born to consanguineous parents. He presented with type 1 diabetes, autoimmune
haematological cytopenia, recurrent chest infections and lymphocytic interstitial
lung disease. The patient was treated with CTLA4-Ig (abatacept) with good outcome
every 2 weeks for a period of 3 months. He developed complete IgG deficiency, but
remarkably, histological examination revealed germinal centres and plasma cells
in lymphoid and inflamed lung tissue. Further charatecterisation showed these
cells to express IgM but not IgG. This ex vivo analysis suggests that LRBA
mutation confers a defect in class switching despite plasma cell formation.
PMID- 28690851
TI - Combining emotion regulation and mindfulness skills for preventing depression
relapse: a randomized-controlled study.
AB - BACKGROUND: Dialectical behavioral therapy (DBT) skills have become increasingly
used to treat several psychiatric conditions, including major depressive disorder
(MDD). The aim of the study was to investigate the efficacy of an intervention
that combines emotion regulation and mindfulness skills of DBT to prevent
depression relapse/recurrence. METHODS: A total of 75 individuals (79% females;
mean age, 52 years) with a diagnosis of MDD in complete or partial remission were
recruited. Participants were randomly allocated either to an intervention
combining emotion regulation and mindfulness skills (ER + M group, n = 37) or to
a psychoeducative program (n = 38). After the 10-week treatment period,
participants were followed for 1 year. Analyses were run in per-protocol (PP) and
intention-to-treat (ITT) samples. The primary outcome measure was time to
depression relapse/recurrence. RESULTS: ER + M training was not more effective
than the control intervention in preventing depression relapse. However, PP and
ITT analyses showed that participants trained in ER + M presented a significant
reduction in depressive symptoms and overall psychopathology. Based on the PP and
ITT analyses, neither of the interventions were related with an increase in
dispositional mindfulness. CONCLUSIONS: More studies are needed to confirm the
efficacy of ER + M to decrease depressive symptoms and overall psychopathology.
TRIAL REGISTRATION: NCT02747134. Registered on 20 April 2016.
PMID- 28690852
TI - Is polymyxin B-immobilized fiber column ineffective for septic shock? A
discussion on the press release for EUPHRATES trial.
AB - The efficacy of polymyxin B-immobilized (PMX) fiber column on septic shock is
still under debate. Recently, the result from "Evaluating the Use of Polymyxin B
Hemoperfusion in a Randomized controlled trial of Adults Treated for Endotoxemia
and Septic shock (EUPHRATES)" trial has been announced as a press release.
According to that report, less than a 5% mortality difference was recognized in
the "per protocol population" (n = 244, 31.9 vs. 36.9%) and the decrease was not
statistically significant. However, among the patients in refractory shock with a
multiple organ dysfunction score of more than 9 and an EAA between 0.6 and 0.9, a
10.7% reduction in 28-day mortality was recognized (p = 0.0474) when they
received two sessions of hemoperfusion using the PMX fiber column. Since this
favorable effect was obtained from "post hoc" analysis, further study is
expected.
PMID- 28690853
TI - Significantly enhanced lung metastasis and reduced organ NK cell functions in
diet-induced obese rats.
AB - BACKGROUND: Obesity was identified as a major risk factor for malignant diseases,
but underlying mechanisms remain unclear. Natural killer (NK) cells, a pivotal
aspect of innate immunity, are capable of identifying and killing virally
infected and tumor cells. Previous studies have shown altered NK cell functions
in obesity, and the current study aimed to investigate the relationship between
altered NK cell functions and increased cancer risk in obesity. METHODS: To
induce obesity male F344-rats received a high-fat diet (34% fat) or a control
diet (4% fat). Thereafter, syngeneic mammary adenocarcinoma cells (MADB106) or a
vehicle were intravenously (i.v.) injected. 15 min after injection, half of each
group of rats were killed, lungs removed and immunohistochemically stained.
Numbers of NK cells, MADB106 cells and NK cell-tumor cell interactions were
quantified. Twenty-one days after tumor-cell injection the other half group of
rats was killed and lung metastases were counted and relative mRNA concentrations
of different NK cell receptors were determined. RESULTS: After short-term MADB106
challenge, DIO fed animals showed significantly decreased NK cell numbers in the
blood and NK cell-tumor cell interactions in the lung as compared to their
control littermates. Twenty-one days after MADB106 injection, the lungs of the
DIO fed rats showed significantly more lung metastases compared to control
animals, accompanied by reduced relative mRNA concentrations of the activating NK
cell receptor NKG2D. CONCLUSIONS: We conclude that induction of obesity in F344
rats leads to reduced lung NK cell function against tumor cells and results in
significantly enhanced lung metastasis as compared to lean animals. It can be
hypothesized that obesity-induced altered NK cell functions play an important
role in cancer growth and metastasis.
PMID- 28690854
TI - Association between serum uric acid and metabolic syndrome components in
prepubertal obese children (Tanner Stage I) from Nuevo Leon, Mexico - a
preliminary study.
AB - BACKGROUND: Metabolic syndrome (MetS) is a major risk factor for cardiovascular
disease and diabetes. Previous studies in obese children demonstrating a positive
association between serum uric acid (sUA) and components of MetS are confounded
by lack of uniformity in age and pubertal status of children. Therefore, we have
examined the role of sUA in MetS and its components in pre-pubertal children
(Tanner Stage I, age <= 9 years). METHODS: Pre-pubertal obese children (32 boys,
27 girls, age 6-9 years) were recruited from Nuevo Leon, Mexico. For comparison,
an equal number of children with normal body mass index (BMI) in the same age
range (22 Boys, 39 girls, age 6-9 years) were also recruited from the same
community. Presence of MetS and its components was defined according to the
criteria of International Diabetes Federation. Fasting blood was analyzed for
lipids, glucose, insulin, and uric acid. RESULTS: Among the obese children, sUA
was positively associated with insulin resistance and hypertriglyceridemia and
negatively associated with high density lipoprotein-cholesterol (HDLc). Subjects
were three times more likely to have a MetS diagnosis per one unit (md/dL)
difference in sUA. Of the 59 obese pre-pubertal children, 20 were classified as
having MetS defined by the presence of abdominal obesity and two or more of other
components described under methods. Of these, 57.1% (20/61) had sUA between 5.1
and 7.1 mg/dl. CONCLUSIONS: The findings of this study clearly indicate a
positive relationship between uric acid and MetS and its components in pre
pubertal obese children with Tanner stage I and <=9 years of age.
PMID- 28690855
TI - Prevalence of obesity and overweight and its associated factors among registered
pensioners in Ghana; a cross sectional studies.
AB - BACKGROUND: The elderly are faced with health problems such as cardiovascular
diseases, type II diabetes mellitus, kidney disease, arthritis and other
musculoskeletal problems, which can be linked to obesity and overweight. The aim
of this study was to determine the prevalence of obesity and overweight and its
associated factors amongst registered pensioners in Ghana. METHODS: A cross
sectional study was conducted among members of the national pensioners
association of Ghana. 4813 pensioners took part in the study. Thirteen study
centers were used in the study with at least one center per regional capital.
Questionnaires, physical examinations, blood and urine sample examinations were
carried out. RESULTS: Overall, 16.3% of the pensioners were obese while 30.0%
were overweight. Prevalence of obesity among males and females were 8.0% and
34.5% respectively. Pensioners who were hypertensive had 1.8 times the odds (95%
CI = 1.5-2.0) of being obese/overweight. Serum triglycerides levels of 2.26
mmol/L (200 mg/dL) or more, were associated with 80% chance of obesity and
overweight (OR = 1.8, 95% CI = 1.3 - 2.5). There was 30% increase in arthritis
among obese/overweight pensioners compared to normal/underweight pensioners.
Obesity and overweight pensioners were more likely to be using eyeglass (OR =
1.7, 95% CI = 1.3-2.2) and less likely to report hearing loss (OR = 0.7, 95% CI
=0.5-1.0). CONCLUSION: The prevalence of obesity among the elderly in Ghana is
high. Age had an inverse linear relationship with BMI among pensioners.
Hypertension, arthritis and dyslipidemia were associated with obesity among
registered pensioners.
PMID- 28690856
TI - IT-supported integrated care pathways for diabetes: A compilation and review of
good practices.
AB - INTRODUCTION: Integrated Care Pathways (ICPs) are a method for the mutual
decision-making and organization of care for a well-defined group of patients
during a well-defined period. The aim of a care pathway is to enhance the quality
of care by improving patient outcomes, promoting patient safety, increasing
patient satisfaction, and optimizing the use of resources. To describe this
concept, different names are used, e.g. care pathways and integrated care
pathways. Modern information technologies (IT) can support ICPs by enabling
patient empowerment, better management, and the monitoring of care provided by
multidisciplinary teams. This study analyses ICPs across Europe, identifying
commonalities and success factors to establish good practices for IT-supported
ICPs in diabetes care. METHODS: A mixed-method approach was applied, combining
desk research on 24 projects from the European Innovation Partnership on Active
and Healthy Ageing (EIP on AHA) with follow-up interviews of project
participants, and a non-systematic literature review. We applied a Delphi
technique to select process and outcome indicators, derived from different
literature sources which were compiled and applied for the identification of
successful good practices. RESULTS: Desk research identified sixteen projects
featuring IT-supported ICPs, mostly derived from the EIP on AHA, as good
practices based on our criteria. Follow-up interviews were then conducted with
representatives from 9 of the 16 projects to gather information not publicly
available and understand how these projects were meeting the identified criteria.
In parallel, the non-systematic literature review of 434 PubMed search results
revealed a total of eight relevant projects. On the basis of the selected EIP on
AHA project data and non-systematic literature review, no commonalities with
regard to defined process or outcome indicators could be identified through our
approach. Conversely, the research produced a heterogeneous picture in all
aspects of the projects' indicators. Data from desk research and follow-up
interviews partly lacked information on outcome and performance, which limited
the comparison between practices. CONCLUSION: Applying a comprehensive set of
indicators in a multi-method approach to assess the projects included in this
research study did not reveal any obvious commonalities which might serve as a
blueprint for future IT-supported ICP projects. Instead, an unexpected high
degree of heterogeneity was observed, that may reflect diverse local
implementation requirements e.g. specificities of the local healthcare system,
local regulations, or preexisting structures used for the project setup.
Improving the definition of and reporting on project outcomes could help advance
research on and implementation of effective integrated care solutions for chronic
disease management across Europe.
PMID- 28690857
TI - Advancing integrated care and its evaluation by means of a universal typology.
AB - Health systems around the globe implement integrated care interventions to
address the Triple Aim of simultaneously improving population health, patient
experiences and cost-efficiency. However, the underlying definitions and
conceptualisations of integrated care often differ considerably, which makes
uniform measurement and comparison difficult. Rather than agreeing on one
definition of integrated care, we argue that a universal typology of integrated
care interventions should be developed to enable the comparison of interventions
that are based on different understandings of integrated care. This universal
typology should combine rankable and intangible components with unrankable and
tangible sub-components, and be conceptually sound and flexible. The content of
the typology should be developed by an international consortium of relevant
stakeholders.
PMID- 28690858
TI - Topical rapamycin for facial angiofibromas in tuberous sclerosis complex.
AB - Facial angiofibromas are a common cutaneous manifestation of tuberous sclerosis
complex. Although angiofibromas are usually asymptomatic, they can be highly
disfiguring and can have a significant impact on patient quality of life.
Treatment for facial angiofibromas is challenging. Recently, topical rapamycin
has been proposed as an effective option to treat angiofibromas. Herein is
reported a case of a 27-year-old woman whose facial angiofibromas were
successfully treated with topical rapamycin without relevant side effects.
PMID- 28690859
TI - Case report of a lupus patient with a severe flare and miliary tuberculosis: need
for proper guidelines for management.
AB - Systemic lupus erythematosus (SLE) is an autoimmune disease that is frequently
treated with high doses of corticosteroids and other immunosuppressive drugs.
Thus patients with SLE are at increased risk for infections with several
pathogens including Mycobacterium tuberculosis. There are no established
guidelines available for treatment of tuberculosis in SLE patients with high
disease activity due to lack of relevant studies and management based more on
physician expertise. We report a case of a young SLE patient with high disease
activity index (SLEDAI19) as evidenced by the presence of a vasculitic rash, non
healing ulcer on forearm and proteinuria of >1 g/d along with miliary
tuberculosis. She was treated with intravenous methylprednisolone pulse up to 3 g
and antituberculous therapy, but the result was a fatal outcome. This case report
emphasizes the need for formal guidelines for co-management of active
tuberculosis and SLE with high disease activity.
PMID- 28690860
TI - The detection of a novel insertion mutation in exon 2 of the MEFV gene associated
with familial mediterranean fever in a moroccan family.
AB - Familial Mediterranean fever (FMF) is a hereditary autoinflammatory disease that
is inherited in an autosomal recessive manner and is caused by mutations in the
MEFV gene. As the name indicates, FMF occurs within families and is more common
in individuals of Mediterranean descent than in persons of any other ethnicity.
To date, 314 mutations have been reported. We studied a Moroccan family with a
total of five members, including a mother who was presenting with symptoms of
FMF, while her four children remained asymptomatic. The five patients were
screened by DNA sequencing of exon 2 and exon 10 of the MEFV gene. Then, complete
exome sequencing analysis of the MEFV gene was done for the patients in whom a
novel mutation was detected. This analysis identified a novel single base
Cytosine (C) insertion mutation in the coding region of the MEFV gene, named
c.441dupC (p. Glu148Argfs*5 or E148RfsX5), which resulted in a mutated
Pyrin/Marenostrin protein. This is the first report of a new mutation in exon 2
of the MEFV gene in a Moroccan family. This novel insertion mutation may provide
important information for further studies of FMF pathogenesis.
PMID- 28690861
TI - Whole-exome sequencing analysis of Waardenburg syndrome in a Chinese family.
AB - Waardenburg syndrome (WS) is a dominantly inherited, genetically heterogeneous
auditory-pigmentary syndrome characterized by non-progressive sensorineural
hearing loss and iris discoloration. By whole-exome sequencing (WES), we
identified a nonsense mutation (c.598C>T) in PAX3 gene, predicted to be disease
causing by in silico analysis. This is the first report of genetically diagnosed
case of WS PAX3 c.598C>T nonsense mutation in Chinese ethnic origin by WES and in
silico functional prediction methods.
PMID- 28690862
TI - A novel three-base duplication, E243dup, of GFAP identified in a patient with
Alexander disease.
AB - Alexander disease (AxD) is a rare hereditary neurodegenerative disorder caused by
glial fibrillary acidic protein (GFAP) gene mutations, most of which are missense
mutations. We present an AxD case with a novel de novo three-base duplication
mutation in GFAP resulting in E243dup.
PMID- 28690863
TI - Fertility preservation training for obstetrics and gynecology fellows: a highly
desired but non-standardized experience.
AB - BACKGROUND: Despite a large body of data suggesting that delivery of fertility
care to cancer patients is inconsistent and frequently insufficient, there is a
paucity of literature examining training in fertility preservation for those
physicians expected to discuss options or execute therapy. The study objective
was to compare fertility preservation training between Reproductive Endocrinology
& Infertility (REI) and Gynecologic Oncology (GYN ONC) fellows and assess the
need for additional education in this field. METHODS: A 38-item survey was
administered to REI and GYN ONC fellows in the United states in April 2014.
Survey items included: 1) Clinical exposure, perceived quality of training, and
self-reported knowledge in fertility preservation; 2) an educational needs
assessment of desire for additional training in fertility preservation. RESULTS:
Seventy-nine responses were received from 137 REI and 160 GYN ONC fellows
(response rate 27%). REI fellows reported seeing significantly more fertility
preservation patients and rated their training more favorably than GYN ONC
fellows (48% of REI fellows versus 7% of GYN ONC fellows rated training as
'excellent', p < 0.001). A majority of all fellows felt discussing fertility
preservation was 'very important' but fellows differed in self-reported ability
to counsel patients, with 43% of REI fellows and only 4% of GYN ONC fellows able
to counsel patients 'all the time' (p = 0.002). Seventy-six percent of all
fellows felt more education in fertility preservation was required, and 91% felt
it should be a required component of fellowship training. CONCLUSION: Significant
variability exists in fertility preservation training for REI and GYN ONC
fellows, with the greatest gap seen for GYN ONC fellows, both in perceived
quality of fertility preservation training and number of fertility preservation
patients seen. A majority of fellows in both disciplines support the idea of a
standardized multi-disciplinary curriculum in fertility preservation.
PMID- 28690864
TI - Surgical site infections after cesarean delivery: epidemiology, prevention and
treatment.
AB - Cesarean delivery (CD) is one of the most common procedures performed in the
United States, accounting for 32% of all deliveries. Postpartum surgical site
infection (SSI), wound infection and endometritis is a major cause of prolonged
hospital stay and poses a burden to the health care system. SSIs complicate a
significant number of patients who undergo CD - 2-7% will experience sound
infections and 2-16% will develop endometritis. Many risk factors for SSI have
been described. These include maternal factors (such as tobacco use; limited
prenatal care; obesity; corticosteroid use; nulliparity; twin gestations; and
previous CD), intrapartum and operative factors (such as chorioamnionitis;
premature rupture of membranes; prolonged rupture of membranes; prolonged labor,
particularly prolonged second stage; large incision length; subcutaneous tissue
thickness > 3 cm; subcutaneous hematoma; lack of antibiotic prophylaxis;
emergency delivery; and excessive blood loss), and obstetrical care on the
teaching service of an academic institution. Effective interventions to decrease
surgical site infection include prophylactic antibiotic use (preoperative first
generation cephalosporin and intravenous azithromycin), chlorhexidine skin
preparation instead of iodine, hair removal using clippers instead of razors,
vaginal cleansing by povidone-iodine, placental removal by traction of the
umbilical cord instead of by manual removal, suture closure of subcutaneous
tissue if the wound thickness is >2 cm, and skin closure with sutures instead of
with staples. Implementation of surgical bundles in non-obstetric patients has
been promising., Creating a similar patient care bundle comprised evidence-based
elements in patients who undergo CD may decrease the incidence of this major
complication. Each hospital has the opportunity to create its own CD surgical
bundle to decrease surgical site infection.
PMID- 28690865
TI - Delaying pigs from the normal production flow is associated with health problems
and poorer performance.
AB - BACKGROUND: Delaying pigs from advancing through the production stages could have
a negative impact on their health and performance. The objective of this study
was to investigate the possible implications of delaying pigs from the normal
production flow on pig health and performance in a farrow-to-finish commercial
farm with a self-declared All-In/All-Out (AIAO) management. RESULTS: Three flows
of pigs were defined, flow 1 (i.e. pigs that followed the normal production flow;
8 weeks in the nursery stage, 4 weeks in the growing stage and 8 weeks in the
finisher stage), flow 2 (i.e. pigs delayed 1 week from advancing to the next
production stage) and flow 3 (i.e. pigs delayed >1 week from advancing to the
next production stage). Flow 3 included higher proportions of pigs from first
parity sows and of lighter birth weights. When the 3 flows were matched by parity
and birth weight, pigs in flow 2 were 3.8 times more likely to be lame prior to
slaughter compared with pigs in flow 1. Similarly, pigs in flow 3 were more
likely to be lame prior to slaughter, 4.5 times more likely to present pleurisy,
3.3 times more like to present pericarditis and 4.3 times more likely to have
their heart condemned at slaughter compared with pigs in flow 1. Additionally,
carcasses from pigs in flow 3 were 10 kg lighter compared with carcasses from
pigs in flow 1. CONCLUSION: Delayed pigs were more affected by disease and were
lighter at slaughter. Besides animal welfare issues, these findings could
represent considerable economic loses for pig producers. In practice, delaying
pigs from the normal production flow translates into higher feeding costs,
increase number of days to slaughter and increased labour requirements reducing
production efficiency for the pig operation. In farrow-to-finish farms an 'all
forward' policy (i.e. no pig is left behind from stage to stage and a split
marketing approach is applied when sending pigs to slaughter) might be more
easily adhered to.
PMID- 28690866
TI - Serotonergic neurons in the ventral nerve cord of Chilopoda - a mandibulate
pattern of individually identifiable neurons.
AB - BACKGROUND: Given the numerous hypotheses concerning arthropod phylogeny,
independent data are needed to supplement knowledge based on traditional external
morphology and modern molecular sequence information. One promising approach
involves comparisons of the structure and development of the nervous system.
Along these lines, the morphology of serotonin-immunoreactive neurons in the
ventral nerve cord has been investigated in numerous tetraconate taxa (Crustacea
and Hexapoda). It has been shown that these neurons can be identified
individually due to their comparably low number, characteristic soma position,
and neurite morphology, thus making it possible to establish homologies at the
single cell level. Within Chilopoda (centipedes), detailed analyses of major
branching patterns of serotonin-immunoreactive neurons are missing, but are
crucial for developing meaningful conclusions on the homology of single cells.
RESULTS: In the present study, we re-investigated the distribution and projection
patterns of serotonin-immunoreactive neurons in the ventral nerve cord of three
centipede species: Scutigera coleoptrata, Lithobius forficatus, and Scolopendra
oraniensis. The centipede serotonergic system in the ventral nerve cord contains
defined groups of individually identifiable neurons. An anterior and two
posterior immunoreactive neurons per hemiganglion with contralateral projections,
a pair of ipsilateral projecting lateral neurons (an autapomorphic character for
Chilopoda), as well as a postero-lateral group of an unclear number of cells are
present in the ground pattern of Chilopoda. CONCLUSIONS: Comparisons to the
patterns of serotonin-immunoreactive neurons of tetraconate taxa support the
homology of anterior and posterior neurons. Our results thus support a sister
group relationship of Myriapoda and Tetraconata and, further, a mandibulate
ground pattern of individually identifiable serotonin-immunoreactive neurons in
the ventral nerve cord. Medial neurons are not considered to be part of the
tetraconate ground pattern, but could favor the 'Miracrustacea hypothesis',
uniting Remipedia, Cephalocarida, and Hexapoda.
PMID- 28690867
TI - Determinants of uncontrolled hypertension among clients on anti-retroviral
therapy in Kadoma City, Zimbabwe, 2016.
AB - BACKGROUND: Clients on anti-retroviral therapy (ART) are living longer and have
risk of hypertension. Side effects of medicines and aging increase this risk.
Hypertension prevalence among clients on ART in Kadoma City was estimated to be
30% in 2015. Of these, 61% had uncontrolled hypertension. This was high compared
to 46% of hypertensives in the general population who had uncontrolled
hypertension. We determined factors associated with uncontrolled hypertension
among clients on ART. METHODS: A 1.1 unmatched case control study was conducted.
Interviews, anthropometric measurements and record reviews were to collect data
on demography and medical history. Epi Info 7 was used for univariate, bivariate
analysis and logistic regression. RESULTS: One hundred and fifty-two cases and
152 controls were recruited into the study. Adding salt to dishes regularly aOR =
5.69 (3.19-10.16), body mass index (BMI) above 25 kg/m2 aOR = 2.81 (1.60-4.91)
and history of elevated blood pressure in previous year aOR = 2.34 (1.33-4.13)
were independent risk factors. Independent protective factors were duration more
than 2 years since HIV diagnosis aOR = 0.58 (0.35-0.95), duration less than 5
years since hypertension diagnosis aOR = 0.50 (0.30-0.83) and walking or cycling
as a means of transport aOR = 0.27 (0.16-0.48). CONCLUSION: Adding salt to dishes
regularly, BMI above 25 kg/m2, history of elevated blood pressure in the previous
year, duration more than 2 years since HIV diagnosis, duration less than 5 years
since hypertension diagnosis and walking or cycling as a means of transport were
independently associated with uncontrolled hypertension. Health education on
lifestyle changes like walking and cycling as transport and dietary modification
such as salt intake reduction were recommended.
PMID- 28690868
TI - miRNA-200c-3p is crucial in acute respiratory distress syndrome.
AB - Influenza infection and pneumonia are known to cause much of their mortality by
inducing acute respiratory distress syndrome (ARDS), which is the most severe
form of acute lung injury (ALI). Angiotensin-converting enzyme 2 (ACE2), which is
a negative regulator of angiotensin II in the renin-angiotensin system, has been
reported to have a crucial role in ALI. Downregulation of ACE2 is always
associated with the ALI or ARDS induced by avian influenza virus, severe acute
respiratory syndrome-coronavirus, respiratory syncytial virus and sepsis.
However, the molecular mechanism of the decreased expression of ACE2 in ALI is
unclear. Here we show that avian influenza virus H5N1 induced the upregulation of
miR-200c-3p, which was then demonstrated to target the 3'-untranslated region of
ACE2. Then, we found that nonstructural protein 1 and viral RNA of H5N1
contributed to the induction of miR-200c-3p during viral infection. Additionally,
the synthetic analog of viral double-stranded RNA (poly (I:C)), bacterial
lipopolysaccharide and lipoteichoic acid can all markedly increase the expression
of miR-200c-3p in a nuclear factor-kappaB-dependent manner. Furthermore, markedly
elevated plasma levels of miR-200c-3p were observed in severe pneumonia patients.
The inhibition of miR-200c-3p ameliorated the ALI induced by H5N1 virus infection
in vivo, indicating a potential therapeutic target. Therefore, we identify a
shared mechanism of viral and bacterial lung infection-induced ALI/ARDS via
nuclear factor-kappaB-dependent upregulation of miR-200c-3p to reduce ACE2
levels, which leads increased angiotensin II levels and subsequently causes lung
injury.
PMID- 28690869
TI - The clinical impact of copy number variants in inherited bone marrow failure
syndromes.
AB - Inherited bone marrow failure syndromes (IBMFSs) comprise a genetically
heterogeneous group of diseases with hematopoietic failure and a wide array of
physical malformations. Copy number variants (CNVs) were reported in some IBMFSs.
It is unclear what impact CNVs play in patients evaluated for a suspected
diagnosis of IBMFS. Clinical and genetic data of 323 patients from the Canadian
Inherited Marrow Failure Registry from 2001 to 2014, who had a documented genetic
work-up, were analyzed. Cases with pathogenic CNVs (at least 1 kilobasepairs)
were compared to cases with other mutations. Genotype-phenotype correlations were
performed to assess the impact of CNVs. Pathogenic nucleotide-level mutations
were found in 157 of 303 tested patients (51.8%). Genome-wide CNV analysis by
single nucleotide polymorphism arrays or comparative genomic hybridization arrays
revealed pathogenic CNVs in 11 of 67 patients tested (16.4%). In four of these
patients, identification of CNV was crucial for establishing the correct
diagnosis as their clinical presentation was ambiguous. Eight additional patients
were identified to harbor pathogenic CNVs by other methods. Of the 19 patients
with pathogenic CNVs, four had compound-heterozygosity of a CNV with a nucleotide
level mutation. Pathogenic CNVs were associated with more extensive non
hematological organ system involvement (p=0.0006), developmental delay (p=0.006)
and short stature (p=0.04) compared to nucleotide-level mutations. In conclusion,
a significant proportion of patients with IBMFSs harbor pathogenic CNVs which
were associated with a more extensive non-hematological phenotype in this cohort.
Patients with a phenotype suggestive of IBMFSs but without identification of
pathogenic nucleotide-level mutations should undergo specific testing for CNVs.
PMID- 28690870
TI - Spinal dural arteriovenous fistula: a case series and review of imaging findings.
AB - INTRODUCTION: Spinal dural arteriovenous fistulae (sdAVF) are rare lesions.
Patients typically present with slowly progressive myelopathy that is often
mistaken for degenerative cervical or lumbar stenosis. On spinal magnetic
resonance imaging (MRI), multisegmental T2 hyperintensities along with associated
flow voids are pathognomonic of sdAVF. However, diagnosis can be difficult.
Definitive diagnosis and localization is achieved with complete spinal
angiography. Treatment options include open surgical ligation, endovascular
embolization or multimodality treatment. The purpose of this study is to present
a series of cases to aid in the assessment, diagnosis and treatment of this
unusual pathology. CASE PRESENTATION: We present 10 cases of sdAVF treated at our
center over an 8-year period. Seventy percent of patients were male. The mean age
of presentation was 62.6 years. The most common lesion was a dorsal dural AVF
with single feeder. All patients underwent open surgical ligation, six having
preoperative coil embolization of the radicular artery to allow for
intraoperative localization of the fistula. Eight patients showed improvement
following treatment as graded by the Nurick system. Two patients failed to
improve. None of the patients worsened. One patient had a radiation burn from the
spinal angiogram requiring secondary closure and one patient had a
pseudomeningocele at the site of surgery that resolved. DISCUSSION: The
successful treatment of sdAVF requires a detailed understanding of clinical
presentation and imaging findings to allow for precise treatment. Owing to the
rarity of the condition, clinicians must continue to share their experiences to
advance our knowledge.
PMID- 28690871
TI - Cervical spine epidural abscess: a single center analytical comparison to the
literature.
AB - STUDY DESIGN: Retrospective review of patient charts. OBJECTIVES: Cervical spine
epidural abscess (CSEA) is uncommon. In this study, characteristics of CSEA
patients are described through an institutional analysis and literature review.
SETTING: University-affiliated city hospital. METHODS: The electronic medical
record was searched from 01/2001 to 01/2012. Data on presentation, comorbidities,
diagnostic modalities, pathogens, treatments, and neurological recovery were
collected. RESULTS: Sixteen patients were identified with a mean age of 57.9
years (33-83). Nine were females. Common symptoms were neck/back pain (62.5%),
neurological deficits (62.5%), and fever (31.3%). Comorbidities included
cardiovascular disease (56.3%), renal disease (37.5%), and diabetes mellitus
(37.5%). Lower levels were more likely afflicted (C5-C7). Microorganisms were
commonly Staphylococcus and Streptococcus (68.8%). Eight (50.0%) received surgery
(anterior [87.5%] and posterior [12.5%] cervical fusion and corpectomy [37.5%])
plus antibiotics and 8 (50.0%) were treated with antibiotics only. Patients with
less comorbidities were more likely to receive surgery; more comorbidities were
was associated with a poor prognosis. Eight patients (50%) made had full
neurological recovery, 2 (12.5%) with had minimal recovery, 2 deaths died, and
the remaining (25%) 1 was were sent to a skilled facility and 1or lost to follow
up. CONCLUSIONS: Cervical SEA can be problematic. The vast majority do not
present classically and treatment does vary. It occurs more frequently in the
lower cervical levels. Though antibiotics alone may suffice, surgery is
frequently employed and a multitude of techniques are at the utility of the spine
surgeon. Cardiovascular comorbidities are associated with a poorer outcome. In
order to improve prognosis, management considerations should include both patient
factors and multidisciplinary efforts.
PMID- 28690872
TI - Physiological and lipid profile response to acute exercise at different
intensities in individuals with spinal cord injury.
AB - STUDY DESIGN: Experimental and cross-sectional study. OBJECTIVE: To assess the
immediate effect of exercise on heart rate (HR), oxygen uptake (VO2), pulmonary
ventilation (PV), oxygen pulse (OP), glucose and lipids of wheelchair basketball
players with spinal cord injury (SCI). SETTING: Center of Studies in
Psychobiology and Exercise-Sao Paulo, Brazil. METHODS: In all, nine wheelchair
basketball players with SCI and nine able-bodied controls (C) performed three
exercise sessions at different intensities: ventilatory threshold 1 (VT1), 15%
below VT1 and 15% above VT1 with a duration of ~24-34 min. HR, VO2, PV, OP,
glucose and lipids were analyzed. RESULTS: VO2, PV and OP were significantly
lower in the players with SCI compared to C during the same intensity exercise
sessions. However, the individuals with SCIs demonstrated increases in HR, PV and
OP at similar rates to C. Triglycerides of the SCI group were elevated 30 min
after the exercise session at VT1 compared to values before the exercise session
(P=0.017); this elevation was not observed in group C. For the exercise sessions
15% above VT1, only glucose (P=0.040) and low-density lipoprotein (P=0.012) 30
min after the exercise were elevated in the SCI group compared to group C.
CONCLUSION: We conclude that the SCI group demonstrated increases in HR, PV and
OP but not VO2 with increased intensity of exercise at similar rates as in group
C.
PMID- 28690873
TI - Spinal cord infarction in a sick neonate from predominant haemorrhagic aetiology:
a case report.
AB - INTRODUCTION: Spinal cord injuries in new born infants following a traumatic
delivery or umbilical cord catheterisation due to thromboembolism are well known.
Cases with atraumatic acute onset of neonatal paraplegia have also been described
in preterm babies or babies born small for gestational age with a stormy
postnatal course related to ischaemic aetiology. We describe a rare case of
infarction of the spinal cord from a predominant haemorrhagic aetiology. CASE
PRESENTATION: A term female baby, first child of unrelated parents, was born by
normal vaginal delivery. She had meconium aspiration at birth, leading to severe
respiratory distress, requiring neonatal intensive care admission. At 2 weeks,
she developed new flaccid paraplegia. MRI scan of the spine showed haemorrhagic
infarction of the spinal cord from the level of thoracic inlet, vertebral level
C7-T1. A follow-up MRI scan at 11 months revealed severe atrophy of the cord
distal to C6. At 3 years of age, she had good upper-limb function, diaphragmatic
breathing and flaccid paralysis of lower limbs. DISCUSSION: In an acutely unwell
term infant with symptoms of paralysis or spinal cord damage, haemorrhagic
infarction needs to be considered in the differential diagnosis. To our
knowledge, this is the first reported case of spinal cord injury in a term infant
with a haemorrhagic lesion, and it helps to understand the pathogenesis of
nontraumatic insult.
PMID- 28690874
TI - Sulforaphane-cysteine-induced apoptosis via phosphorylated ERK1/2-mediated maspin
pathway in human non-small cell lung cancer cells.
AB - Sulforaphane (SFN) was demonstrated to induce apoptosis in a variety of cancers
via multiple mechanisms. However, owing to a short half-life in circulation, SFN
was not used for clinical treatment yet. Interestingly, SFN analog, sulforaphane
cysteine (SFN-Cys) has a longer half-life in metabolism, and we previously
demonstrated that SFN-Cys inhibited invasion in human prostate cancer cells.
Here, we would investigate whether SFN-Cys induces apoptosis and find the
underlying mechanisms in human non-small cell lung cancer (NSCLC) cells. Western
blots were used to test the molecular linkages among extracellular signal
regulated kinases 1/2 (ERK1/2) and downstream signal molecules. Flow cytometry
and fluorescence microscopy were used to detect cell death. Cell proliferation
assay showed that SFN-Cys inhibited cell viability following a dose-dependent
manner. Abnormal cell morphology was viewed after the cells were exposed to SFN
Cys. Flow cytometry showed that SFN-Cys induced cell apoptosis via a dose
dependent manner. Further, SFN-Cys triggered the activation of ERK1/2, which
resulted in the upregulation of maspin, Bax, cleaved caspase-3 and downregulation
of pro-caspase-3, Bcl-2, alpha-tubulin. Meanwhile, we demonstrated that
recombinant caspase-3 cleaved alpha-tubulin in the lysate of cells, which were
treated by SFN-Cys. These data indicated that SFN-Cys activated the ERK1/2
mediated mitochondria signaling pathway with maspin upregulation and alpha
tubulin downregulation leading to apoptosis. These findings will help to develop
a novel therapeutic to target NSCLC cells.
PMID- 28690875
TI - Combination of palbociclib and radiotherapy for glioblastoma.
AB - The cyclin-dependent kinase inhibitor, palbociclib has shown compelling efficacy
in breast cancer patients. Several pre-clinical studies of glioblastoma (GBM)
have also shown palbociclib to be efficacious. In this study, we investigated
palbociclib in combination with radiation therapy (RT) for treating GBM. We
tested palbociclib (with and without RT) on four patient-derived cell lines
(PDCLs; RB1 retained; CDKN2A loss). We investigated the impact of therapy on the
cell cycle and apoptosis using flow cytometry, in vitro. Balb/c nude mice were
intracranially injected with the PDCL, GBM-L1 and treated orally with palbociclib
(with and without RT). Overall survival was measured. Palbociclib treatment
resulted in a significant increase in the percentage of cells in the G1 cell
cycle phase. Apoptotic cell death, measured by Annexin V was induced. Palbociclib
combined with RT acted synergistically with the significant impediment of colony
formation. The oral treatment of mice with palbociclib did not show any
significant survival advantage when compared to control mice, however when
combined with RT, a survival advantage of 8 days was observed. Our results
support the use of palbociclib as an adjuvant treatment to RT and warrant
translation to the clinic.
PMID- 28690876
TI - Impact of Monovalent Counter-ions on the Conformation of Flexible
Polyelectrolytes Having Different Molecular Architectures.
AB - We explore the impact of monovalent counter-ions on the molecular conformation of
highly charged flexible polyelectrolytes for a range of molecular topologies
(linear chains, stars, and unknotted and trefoil rings) by molecular dynamics
simulations that include an explicit solvent having short range interaction with
the polyelectrolyte. In particular, we investigate how the counter-ions near the
polyelectrolytes with variable mass influence the average molecular shape. We
also characterize the interfatially "bound" counter-ions by calculating the time
averaged number of interfacial counter-ions, as well as the degree to which the
polyelectrolytes wrap around the counter-ions by calculating the number of
contacts between the counter-ions and the polyelectrolyte.
PMID- 28690877
TI - Colonization with Multidrug-Resistant Bacteria - On the Efficiency of Local
Decolonization Procedures.
AB - The effectiveness of a disinfectant-based decolonization strategy for multidrug
resistant bacteria like extended spectrum beta-lactamase (ESBL)-positive Gram
negative bacteria with or without additional fluoroquinolon and carbapenem
resistance as well as vancomycin-resistant enterococci and methicillin-resistant
Staphylococcus aureus was assessed. Between 2011 and 2015, 25 patients from
Libya, Syria, and the Ukraine with war traumata were treated at the Bundeswehr
hospital Hamburg. The patients were heavily colonized and infected with multidrug
resistant bacteria, altogether comprising 371 distinct combinations of pathogens
and isolation sites. Local disinfection was assessed for effectiveness regarding
successful decolonization of multidrug-resistant bacteria. Altogether, 170 cases
of successful decolonization were observed, comprising 95 (55.8%) such events at
sampling sites that were accessible to disinfecting procedures. The remaining 75
(44.2%) decolonization events had to be considered as spontaneous. In contrast,
95 out of 172 (55.2%) colonized isolation sites that were accessible to
disinfection procedures were successfully decolonized. Patient compliance with
the enforced hygiene procedures was associated with decolonization success.
Systemic antibiotic therapy did not relevantly affect isolation time.
Disinfecting washing moderately supports local decolonization of multidrug
resistant pathogens in comparison with spontaneous decolonization rates if the
patients' compliance with the applied hygiene procedures is ensured.
PMID- 28690878
TI - The Guanine-Nucleotide Exchange Factor Caldag Gefi Fine-Tunes Functional
Properties of Regulatory T Cells.
AB - Using quantitative phosphopeptide sequencing of unstimulated versus stimulated
primary murine Foxp3+ regulatory and Foxp3- conventional T cells (Tregs and
Tconv, respectively), we detected a novel and differentially regulated tyrosine
phosphorylation site within the C1 domain of the guanine-nucleotide exchange
factor CalDAG GEFI. We hypothesized that the Treg-specific and activation
dependent reduced phosphorylation at Y523 allows binding of CalDAG GEFI to
diacylglycerol, thereby impacting the formation of a Treg-specific immunological
synapse. However, diacylglycerol binding assays of phosphomutant C1 domains of
CalDAG GEFI could not confirm this hypothesis. Moreover, CalDAG GEFI-/- mice
displayed normal Treg numbers in thymus and secondary lymphoid organs, and CalDAG
GEFI-/- Tregs showed unaltered in vitro suppressive capacity when compared to
CalDAG GEFI+/+ Tregs. Interestingly, when tested in vivo, CalDAG GEFI-/- Tregs
displayed a slightly reduced suppressive ability in the transfer colitis model
when compared to CalDAG GEFI+/+ Tregs. Additionally, CRISPR-Cas9-generated CalDAG
GEFI-/- Jurkat T cell clones showed reduced adhesion to ICAM-1 and fibronectin
when compared to CalDAG GEFI-competent Jurkat T cells. Therefore, we speculate
that deficiency in CalDAG GEFI impairs adherence of Tregs to antigen-presenting
cells, thereby impeding formation of a fully functional immunological synapse,
which finally results in a reduced suppressive potential.
PMID- 28690879
TI - Epidemiological Characteristics and Clinical Outcome of HIV-Related Tuberculosis
in a Population of TB Patients in South-western Nigeria.
AB - Tuberculosis (TB) is the second leading cause of death from infectious disease
globally with its impact more dramatic in resource limited settings. Individuals
with human immunodeficiency virus (HIV) infection who also develop tuberculosis
represent a significant challenge to TB control. This study was carried out to
determine the prevalence of TB-HIV coinfection and pattern of infection among TB
patients. We also compared treatment outcome among coinfected patients with those
not coinfected. A six-year retrospective review of records of patients managed at
the Tuberculosis Treatment Center of the LAUTECH Teaching Hospital, South-Western
Nigeria from January 2009 to December 2014 was carried out. One hundred and five
(26.3%) of the 399 TB patients seen in the study period were coinfected with HIV.
About 10% of the subjects had extrapulmonary tuberculosis. Treatment failure was
significantly worse among patients who had both HIV and TB compared with those
who had TB only (49.5% vs. 32%, p = 0.001). Death rate was also higher in the
coinfected individuals implying a poorer clinical outcome. High prevalence of TB
HIV coinfection and poor treatment outcome in this group of individuals, though
predictable, calls for a more concerted effort in the management of TB-HIV
coinfection.
PMID- 28690880
TI - The Prevalence of CTX-M-15 Extended-spectrum beta-Lactamases Among Salmonella
spp. and Shigella spp. Isolated from three Iranian Hospitals.
AB - Bacterial antimicrobial resistance mediated by the production of extended
spectrum beta-lactamases (ESBLs) is considered a major threat for treatment of
Salmonella and Shigella infections. This study aimed to investigate antibiotic
resistance patterns of Salmonella and Shigella spp. and presence of CTX-M from
three teaching hospitals in Iran. In the present study, 58 clinical Shigella and
91 Salmonella isolates were recovered between 2009 and 2013 from 3 teaching
hospitals in Iran. After culture and antimicrobial susceptibility testing, ESBL
positive isolates were subjected to further investigations. These included
polymerase chain reaction (PCR) amplification and DNA sequencing of blaCTX-M-15
encoding plasmid. In both genera, high sensitivity to gentamicin and amikacin,
but high resistance to ampicillin, tetracycline, and trimethoprim
sulfamethoxazole, was found. Molecular investigation showed that 31.8% isolates
of Salmonella spp. and 34.48% isolates of Shigella spp. were CTX-M positive and
all of them were also positive for ISEcpI. Protein translation, comparing with
reference sequences, showed that all CTX-M isolates belong to CTX-M-15. The
present study suggests that the resistance of ESBLs-producing Salmonella and
Shigella spp. in Iran hospitals is very serious. Therefore, strategies to
minimize the spread of ESBL-producing isolates should be implemented.
PMID- 28690881
TI - Small Intestinal Pro-Inflammatory Immune Responses Following Campylobacter Jejuni
Infection of Secondary Abiotic IL-10-/- Mice Lacking Nucleotide-Oligomerization
Domain-2.
AB - Host immune responses are crucial for combating enteropathogenic infections
including Campylobacter jejuni. Within 1 week following peroral C. jejuni
infection, secondary abiotic IL-10-/- mice develop severe immunopathological
sequelae affecting the colon (ulcerative enterocolitis). In the present study, we
addressed whether pathogen-induced pro-inflammatory immune responses could also
be observed in the small intestines dependent on the innate receptor nucleotide
oligomerization-domain-protein 2 (Nod2). Within 7 days following peroral
infection, C. jejuni stably colonized the gastrointestinal tract of both IL-10-/-
mice lacking Nod2 (Nod2-/- IL-10-/-) and IL-10-/- controls displaying bloody
diarrhea with similar frequencies. Numbers of apoptotic and regenerating
epithelial cells increased in the small intestines of C. jejuni-infected mice of
either genotype that were accompanied by elevated ileal T and B lymphocyte
counts. Notably, ileal T cell numbers were higher in C. jejuni-infected Nod2-/-
IL-10-/- as compared to IL-10-/- counterparts. Furthermore, multifold increased
concentrations of pro-inflammatory cytokines including IFN-gamma, TNF, and MCP-1
could be measured in small intestinal ex vivo biopsies derived from C. jejuni
infected mice of either genotype. In conclusion, C. jejuni-induced pro
inflammatory immune responses affected the small intestines of both Nod2-/- IL-10
/- and IL-10-/- mice, whereas ileal T lymphocyte numbers were even higher in the
former.
PMID- 28690882
TI - Photoinactivation of Legionella Rubrilucens by Visible Light.
AB - In this study, the photoinactivation of Legionella by visible light is
investigated. The success of this approach would offer new prospects for
technical water disinfection and maybe even for therapeutic measures in cases of
Legionella infections. Therefore, Legionella rubrilucens was dispensed on
buffered charcoal yeast extract medium agar plates and illuminated with different
doses of violet light generated by 405 nm light-emitting diodes (LEDs). A strong
photoinactivation effect was observed. A dose of 125 J/ cm2 reduced the bacterial
concentration by more than 5 orders of magnitude compared to Legionella on
unirradiated agar plates. The necessary dose for a one log-level reduction was
about 24 J/cm2. These results were obtained for extracellular L. rubrilucens, but
other Legionella species may exhibit a similar behavior.
PMID- 28690883
TI - World Malaria Day: Our story with malaria in Oman.
PMID- 28690884
TI - Hepatic or Cystic Artery Pseudoaneurysms Following a Laparoscopic
Cholecystectomy: Literature review of aetiopathogenesis, presentation, diagnosis
and management.
AB - Pseudoaneurysms (PSAs) of the hepatic and/or cystic artery are a rare
complication following a laparoscopic cholecystectomy (LC). Generally, PSA cases
present with haemobilia several weeks following the procedure. Transarterial
embolisation (TAE) is considered the optimal management approach. We report a 70
year-old woman who presented to the Sultan Qaboos University Hospital, Muscat,
Oman, in 2016 with massive hemoperitoneum two weeks after undergoing a LC
procedure in another hospital. She was successfully managed using coil TAE. An
extensive literature review revealed 101 cases of hepatic or cystic artery PSAs
following a LC procedure. Haemobilia was the main presentation (85.1%) and the
mean time of postoperative presentation was 36 days. The hepatic artery was
involved in most cases (88.1%), followed by the cystic artery (7.9%) and a
combination of both (4.0%). Most cases were managed with TAE (72.3%), with a
94.5% success rate. The overall mortality rate was 2.0%.
PMID- 28690885
TI - Cancer Research in the Arab World: A review of publications from seven countries
between 2000-2013.
AB - This review aimed to examine trends in cancer research in the Arab world and
identify existing research gaps. A search of the MEDLINE(r) database (National
Library of Medicine, Bethesda, Maryland, USA) was undertaken for all cancer
related publications published between January 2000 and December 2013 from seven
countries, including Bahrain, Kuwait, Iraq, Lebanon, Morocco, Palestine and
Sudan. A total of 1,773 articles were identified, with a significant increase in
yearly publications over time (P <0.005). Only 30.6% of the publications included
subjects over the age of 50 years old. There was a dearth of cross
sectional/correlational studies (8.8%), randomised controlled trials (2.4%) and
systematic reviews/meta-analyses (1.3%). Research exploring cancer associations
mainly considered social and structural determinants of health (27.1%), followed
by behavioural risk factors (14.1%), particularly tobacco use. Overall, more
cancer research is needed in the Arab world, particularly analytical studies with
high-quality evidence and those focusing on older age groups and associations
with physical activity and diet.
PMID- 28690886
TI - Breastfeeding Trends and Determinants: Implications and recommendations for Gulf
Cooperation Council countries.
AB - Optimal breastfeeding practices entail the early initiation of breastfeeding soon
after delivery of the baby, exclusive breastfeeding for the first six months of
life and the continuation of breastfeeding complemented by solid food up until
two years of age. Breastfeeding has wide-ranging health benefits for both the
mother and her child; however, many factors contribute to low rates of exclusive
breastfeeding. This article highlights the benefits of optimal breastfeeding as
well as trends and determinants associated with breastfeeding both worldwide and
in Gulf Cooperation Council (GCC) countries. Strategies to optimise breastfeeding
and overcome breastfeeding barriers in the GCC region are recommended, including
community health and education programmes and 'baby-friendly' hospital
initiatives. Advocates of breastfeeding are needed at the national, community and
family levels. In addition, more systematic research should be conducted to
examine breastfeeding practices and the best strategies to promote breastfeeding
in this region.
PMID- 28690887
TI - Prevention of gamma-Radiation-Induced DNA Damage in Human Lymphocytes Using a
Serine-Magnesium Sulfate Mixture.
AB - OBJECTIVES: Ionising radiation has deleterious effects on human cells. N
acetylcysteine (NAC) and cysteine, the active metabolite of NAC, are well-known
radioprotective agents. Recently, a serine-magnesium sulfate combination was
proposed as an antidote for organophosphate toxicity. This study aimed to
investigate the use of a serine-magnesium sulfate mixture in the prevention of
gamma-radiation-induced DNA damage in human lymphocytes as compared to NAC and
cysteine. METHODS: This study was carried out at the Iran University of Medical
Sciences, Tehran, Iran, between April and September 2016. Citrated blood samples
of 7 mL each were taken from 22 healthy subjects. Each sample was divided into 1
mL aliquots, with the first aliquot acting as the control while the second was
exposed to 2 Gy of gamma-radiation at a dose rate of 102.7 cGy/minute. The
remaining aliquots were separately incubated with 600 MUM concentrations each of
serine, magnesium sulfate, serine-magnesium sulfate, NAC and cysteine before
being exposed to 2 Gy of gamma-radiation. Lymphocytes were isolated using a
separation medium and methyl-thiazole-tetrazolium and comet assays were used to
evaluate cell viability and DNA damage, respectively. RESULTS: The serine
magnesium sulfate mixture significantly increased lymphocyte viability and
reduced DNA damage in comparison to serine, magnesium sulfate, NAC or cysteine
alone (P <0.01 each). CONCLUSION: The findings of the present study support the
use of a serine-magnesium sulfate mixture as a new, non-toxic, potent and
efficient radioprotective agent.
PMID- 28690888
TI - Underwater Acoustic Source Localisation Among Blind and Sighted Scuba Divers:
Comparative study.
AB - OBJECTIVES: Many blind individuals demonstrate enhanced auditory spatial
discrimination or localisation of sound sources in comparison to sighted
subjects. However, this hypothesis has not yet been confirmed with regards to
underwater spatial localisation. This study therefore aimed to investigate
underwater acoustic source localisation among blind and sighted scuba divers.
METHODS: This study took place between February and June 2015 in Elba, Italy, and
involved two experimental groups of divers with either acquired (n = 20) or
congenital (n = 10) blindness and a control group of 30 sighted divers. Each
subject took part in five attempts at an under-water acoustic source localisation
task, in which the divers were requested to swim to the source of a sound
originating from one of 24 potential locations. The control group had their sight
obscured during the task. RESULTS: The congenitally blind divers demonstrated
significantly better underwater sound localisation compared to the control group
or those with acquired blindness (P = 0.0007). In addition, there was a
significant correlation between years of blindness and underwater sound
localisation (P <0.0001). CONCLUSION: Congenital blindness was found to
positively affect the ability of a diver to recognise the source of a sound in an
underwater environment. As the correct localisation of sounds underwater may help
individuals to avoid imminent danger, divers should perform sound localisation
tests during training sessions.
PMID- 28690889
TI - Imbalances in T Cell-Related Transcription Factors Among Patients with
Hashimoto's Thyroiditis.
AB - OBJECTIVES: Imbalances in effector T cell functioning have been associated with a
number of autoimmune diseases, including Hashimoto's thyroiditis (HT).
Differentiation of effector T helper (Th) 1, Th2, Th17 and regulatory T cell
(Treg) lymphocytes is regulated by transcription factors, including Th1-specific
T box (T-bet), GATA binding protein-3 (GATA3), retinoid-related orphan receptor
(ROR)-alpha and forkhead box P3 (FOXP3). This study aimed to investigate Th1/Th2,
Th1/Treg, Th2/Treg and Th17/Treg balances at the level of these transcription
factors. METHODS: This study took place between October 2015 and August 2016.
Peripheral blood mononuclear cells were collected from a control group of 40
healthy women recruited from the Zahedan University of Medical Sciences, Zahedan,
Iran, and a patient group of 40 women with HT referred to the Hazrat Ali Asghar
Hospital, Zahedan. Total ribonucleic acid extraction was performed and the gene
expression of transcription factors was quantitated using a real-time polymerase
chain reaction technique. RESULTS: Expression of T-bet and GATA3 was
significantly elevated, while FOXP3 expression was significantly diminished among
HT patients in comparison with the controls (P = 0.03, 0.01 and 0.05,
respectively). Expression of RORalpha was higher among HT patients, although this
difference was not significant (P = 0.15). Expression of T-bet/FOXP3, GATA3/FOXP3
and RORalpha/FOXP3 ratios were increased among HT patients in comparison with the
controls (P <0.02, <0.01 and <0.01, respectively). CONCLUSION: These results
indicate that HT patients have imbalances in Th1/Treg, Th2/Treg and Th17/Treg
lymphocytes at the level of the transcription factors, deviating towards Th1, Th2
and Th17 cells. Correction of these imbalances may therefore be therapeutic.
PMID- 28690890
TI - Development and Validation of a Culturally-Tailored Breast Cancer Health
Education Programme for Arab Women.
AB - OBJECTIVES: This study aimed to develop and validate a health education programme
to encourage breast cancer awareness and early detection behaviours among Arab
women. METHODS: This study took place between December 2015 and March 2016. The
Enabling Systems Raising Awareness model was used to develop a breast cancer
health education programme which was subsequently implemented by trained health
educators at three female-only fitness clubs in Muscat, Oman. Breast cancer
knowledge among 53 women was assessed using the breast module of the Cancer
Awareness Measure before and after each health education session. Overall pre-
and post-session knowledge scores were then compared. Additionally, three focus
group discussions were conducted with 10 participants from each location.
Thematic analysis was used to analyse the transcribed discussions and collect
feedback on the programme. RESULTS: The health education sessions resulted in a
statistically significant increase in overall mean knowledge scores (P <0.001).
Participants also reported significantly improved intentions to undertake early
detection practices (P <0.001). The focus group discussions yielded distinct
themes and valuable feedback which can be utilised in the future to create an
improved version of the programme. CONCLUSION: While the health education
programme significantly improved breast cancer and early detection knowledge
among a cohort of Arab women, it still required critical improvements in terms of
structure and administration. Additional studies are required in order to
evaluate long-term behavioural outcomes resulting from the improved programme.
PMID- 28690891
TI - The Accuracy of the BroselowTM Pediatric Emergency Tape for Weight Estimation in
an Omani Paediatric Population.
AB - OBJECTIVES: This study aimed to evaluate the accuracy of the BroselowTM Pediatric
Emergency Tape (BT) for estimating weight in an Omani paediatric population at a
tertiary care hospital. METHODS: This retrospective cross-sectional study was
conducted during July 2015. The electronic medical records of Omani outpatients
<14 years old attending the Sultan Qaboos University Hospital, Muscat, Oman,
between July 2009 and June 2013 were reviewed for recorded height and weight
data. The BT Version 2002A was used to predict weight based on actual height
measurements. Predicted weight measurements were then compared with actual weight
to determine the accuracy of the estimation. RESULTS: A total of 3,339 children
were included in the study, of which 43.5% were female and 56.5% were male. The
mean age was 6.4 +/- 3.1 years and the mean height was 93.2 +/- 23.5 cm. The mean
actual weight was 13.9 +/- 6.7 kg while the mean BT-predicted weight was 14.4 +/-
6.9 kg. The BT-predicted weight estimations correlated significantly with actual
weight measurements (intraclass correlation coefficient: 0.97; P <0.001). A Bland
Altman analysis indicated that the BT performed well when estimating weight among
Omani children, with an overestimation of only 0.5 kg for the entire cohort.
CONCLUSION: The BT was found to be an effective tool for estimating weight
according to body length in an Omani paediatric population. It should therefore
be considered for use in emergency situations when actual weight cannot be
determined.
PMID- 28690892
TI - Outcomes of Multi-Trauma Road Traffic Crashes at a Tertiary Hospital in Oman:
Does attendance by trauma surgeons versus non-trauma surgeons make a difference?
AB - OBJECTIVES: Trauma surgeons are essential in hospital-based trauma care systems.
However, there are limited data regarding the impact of their presence on the
outcome of multi-trauma patients. This study aimed to assess the outcomes of
multi-trauma road traffic crash (RTC) cases attended by trauma surgeons versus
those attended by non-trauma surgeons at a tertiary hospital in Oman. METHODS:
This retrospective study was conducted in December 2015. A previously published
cohort of 821 multi-trauma RTC patients admitted between January and December
2011 to the Sultan Qaboos University Hospital, Muscat, Oman, were reviewed for
demographic, injury and hospitalisation data. In-hospital mortality constituted
the main outcome, with admission to the intensive care unit, operative
management, intubation and length of stay constituting secondary outcomes.
RESULTS: A total of 821 multi-trauma RTC cases were identified; of these, 60
(7.3%) were attended by trauma surgeons. There was no significant difference in
mortality between the two groups (P = 0.35). However, patients attended by trauma
surgeons were significantly more likely to be intubated, admitted to the ICU and
undergo operative interventions (P <0.01 each). The average length of hospital
stay in both groups was similar (2.6 versus 2.8 days; P = 0.81). CONCLUSION: No
difference in mortality was observed between multi-trauma RTC patients attended
by trauma surgeons in comparison to those cared for by non-trauma surgeons at a
tertiary centre in Oman.
PMID- 28690893
TI - Blood Culture Contaminants in a Paediatric Population Retrospective study from a
tertiary hospital in Oman.
AB - OBJECTIVES: Most children presenting with febrile illness require a blood culture
to determine the causative organism as well as its sensitivity to antibiotics.
However, false-positive results lead to unnecessary hospitalisations,
prescriptions and tests. This study aimed to evaluate the impact of false
positive blood cultures among a paediatric population at a tertiary hospital in
Oman. METHODS: This retrospective study included all 225 children <13 years old
with positive blood cultures who presented to the Sultan Qaboos University
Hospital, Muscat, Oman, between July 2011 and December 2013. Blood cultures were
reviewed to determine whether they were true-positive or contaminated. RESULTS: A
total of 344 positive blood cultures were recorded during the study period, of
which 185 (53.8%) were true-positive and 159 (46.2%) were contaminated. Most true
positive isolates (26.5%) were coagulase-negative Staphylococcus spp. (CONS)
followed by Escherichia coli (9.7%), while the majority of contaminated isolates
were CONS (67.9%) followed by Streptococcus spp. (6.9%). Children with
contaminated cultures were significantly younger (P <0.001) while those with true
positive cultures required significantly more frequent hospital admissions,
longer hospital stays and more frequent antibiotic prescriptions (P <0.001 each).
Chronic illness and mortality was significantly more frequent among those with
true-positive cultures (P <0.001 and 0.04, respectively). While white blood cell
and absolute neutrophil counts were significantly higher in true-positive
cultures (P <0.001 each), there was no significant difference in C-reactive
protein (CRP) level (P = 0.791). CONCLUSION: In this population, CRP level was
not an adequate marker to differentiate between true- and false-positive
cultures. A dedicated well-trained phlebotomy team for paediatric patients is
essential.
PMID- 28690894
TI - Gender Differences in Heart Rate Variability Among Individuals Undergoing Regular
Resistance Training Preliminary observations.
AB - OBJECTIVES: Frequency-domain analysis of heart rate variability (HRV) is an
effective tool to evaluate autonomic balance. This study aimed to investigate
gender differences in HRV among individuals undergoing regular resistance
training. METHODS: This preliminary cross-sectional study was conducted from
April to September 2016 in Joao Pessoa, Paraiba, Brazil. The low-frequency (LF),
high-frequency (HF) and LF/HF ratio components of HRV spectral analysis were
analysed among 22 men and 27 women undergoing regular resistance training.
RESULTS: Among the male participants, the LF component was significantly
increased compared to females in both the supine (1,171 +/- 192 versus 545 +/- 74
ms2; P = 0.0067) and upright (1,824 +/- 260 versus 738 +/- 133; P = 0.0011)
positions. The LF/HF ratio was also significantly increased in both positions
among male participants (P <0.0500 each). CONCLUSION: These preliminary data
suggest a possible gender difference in the HRV of individuals undergoing
resistance training.
PMID- 28690895
TI - Discrimination Between Drug Abuse and Medical Therapy: Case report of a
tranylcypromine overdose-related fatality.
AB - Tranylcypromine is an effective antidepressant from the class of monoamine
oxidase inhibitors and is structurally related to amphetamine. However, reports
differ regarding the potential metabolism of tranylcypromine to amphetamine and
methamphetamine within the human body. We report a 25-year-old woman with severe
depression who died due to a fatal tranylcypromine overdose in 2016. She had been
prescribed tranylcypromine one day previously and had no history of previous
suicide attempts or substance abuse. The body was transferred to a forensic
medicine department in Tehran, Iran for the autopsy. A urine sample was positive
for tranylcypromine, amphetamine and methamphetamine using gas
chromatography/mass spectrometry after derivatisation with heptafluorobutyric
acid. As amphetamines were present in the urine sample, it was assumed that the
tranylcypromine had been converted to amphetamines metabolically. As such, it is
possible that the legitimate use of certain prescription drugs may complicate the
interpretation of test results for illegal drugs.
PMID- 28690896
TI - Late Diagnosis of 5-alpha-Reductase Type 2 Deficiency in an Adolescent Girl with
Primary Amenorrhoea.
AB - Deficiency of the 5-alpha-reductase enzyme has been found to affect male sexual
development. We report an 18-year-old patient who was referred to an
endocrinology clinic in Jizan, Saudi Arabia, in April 2014 with primary
amenorrhoea, virilisation and a lack of secondary sex characteristics. As female
external genitalia were present at birth, she had been raised as a female.
Magnetic resonance imaging revealed no uterine or ovarian tissue in the pelvis
and the presence of a scrotal sac. She was diagnosed with 5-alpha-reductase type
2 deficiency, a 46,XY disorder of sexual development. Typically, affected males
have pseudovaginal perineoscrotal hypospadias and ambiguous genitalia at birth.
Individuals who have been raised as female manifest characteristics of
virilisation at puberty, including deepening of the vocal tone, phallus
enlargement, scrotal hyperpigmentation and increased muscle mass.
PMID- 28690897
TI - A Case of Multiple Myeloma Presenting with Diabetes Insipidus.
AB - Multiple myeloma (MM) can present with involvement of the central nervous system
in the form of nerve palsy, plasma cell masses or, rarely, with endocrinological
effects due to involvement of the pituitary gland. Usually, in such cases, the
disease has a rapid progression and poor prognosis. We report a 52-year-old man
who was admitted to the Kolkata Medical College, Kolkata, India, in 2016 with a
prolonged low-grade fever and hypernatremia. Shortly afterwards, the patient
began to complain of increased urinary frequency and drowsiness. The
hypernatremia was treated with intranasal desmopressin and free water
replacement. Serum protein electrophoresis and an immunofixation study revealed
an immunoglobulin G-kappa monoclonal band. Magnetic resonance imaging of the
pituitary gland revealed the absence of a posterior bright spot and spotty
infiltration of the pituitary fossa. A bone marrow biopsy confirmed a diagnosis
of cranial diabetes insipidus due to posterior pituitary MM infiltration.
PMID- 28690898
TI - Delayed Treatment Response in a Neonate with Multisystem Langerhans Cell
Histiocytosis Case report and review of literature.
AB - Langerhans cell histiocytosis (LCH) is a rare proliferative disorder of the
Langerhans cells, which are part of the mononuclear phagocytic system. The
disorder varies in terms of the extent of the disease, its natural course and
patient outcomes. While skin rashes are a common presentation of neonatal LCH,
other systems or organs may also be involved. Delays in the diagnosis of neonatal
LCH may occur due to its non-specific presentation and a lack of awareness of the
condition among doctors. We report a two-month-old male neonate who presented to
the Chacha Nehru Bal Chikitsalya hospital, New Delhi, India, in 2016 after the
onset of pulmonary symptoms. He had been noted to have a generalised rash which
had progressively worsened from 15 days of age. Following a skin biopsy and chest
imaging, he was diagnosed with multisystem LCH with risk organ involvement. There
was a delayed response to combined chemotherapy with no major side-effects.
PMID- 28690899
TI - Struma Ovarii with Pseudo-Meigs' Syndrome and Raised Cancer Antigen-125 Levels
Masquerading as an Ovarian Carcinoma Case report and literature review.
AB - The monodermal teratoma struma ovarii is a rare ovarian tumour; however, struma
ovarii presenting with pseudo-Meigs' syndrome and raised cancer antigen (CA)-125
levels is even rarer. In elderly patients, this presentation can potentially lead
to a misdiagnosis of a malignant ovarian carcinoma, resulting in unnecessary
extensive surgery. We report a 55-year-old female who presented to the Lok Nayak
Jai Prakash Narayan Hospital, New Delhi, India, in 2016 with progressive
abdominal discomfort, fatigue and abdominal distention. Clinical and radiological
features were indicative of a malignant ovarian tumour and ascites. Serum CA-125
levels were elevated at 258 U/mL. A left-sided salpingo-oophorectomy was
performed, after which the serum CA-125 levels normalised. There was no evidence
of recurrence at a six-month follow-up. A frozen section procedure confirmed the
diagnosis of a struma ovarii. This rare condition should be considered as a
differential diagnosis in patients presenting with ovarian masses, ascites and
raised CA-125 levels.
PMID- 28690901
TI - Use of Cone-Beam Computed Tomography in the Diagnosis and Treatment of an Unusual
Canine Abnormality.
AB - Diagnosis and treatment planning are important for successful endodontic
treatment. We report a 24-year old male who presented to the Government Dental
College in Kozhikode, Kerala, India, in 2015 with pain in his right upper canine.
A digital periapical radiograph indicated the presence of a supernumerary tooth
superimposing the root of the canine. However, cone-beam computed tomography
(CBCT) confirmed that the supernumerary tooth was an illusion and that the canine
root had a sharp invagination involving the labial and pulpal dentin surfaces,
with evidence of periapical bone destruction. A blunt resection was performed at
the level of the invagination and the resected end was filled with a dentin
substitute. At a one-year follow-up, the patient was asymptomatic and the
periapical region appeared to be healing well. This report highlights the
importance of CBCT in visualising abnormal canine morphology, thus allowing
appropriate endodontic treatment.
PMID- 28690900
TI - Solitary Peripheral Osteoma of the Hard Palate Case report and literature review.
AB - Osteomas are benign slow-growing osteogenic lesions of unknown aetiology which
can be central, peripheral or extraskeletal. Peripheral osteomas of the maxilla
are very uncommon. We report a 72-year-old female patient who presented to the
Department of Oral & Maxillofacial Surgery, Dental School of Athens, Athens,
Greece, in 2015 with swelling of the palate following a tooth extraction.
Clinical and radiographical features were indicative of a solitary peripheral
osteoma of the hard palate. An excisional biopsy and histological examination of
the lesion confirmed the diagnosis. No complications occurred during the
postoperative period and there was no evidence of recurrence at a one-year follow
up.
PMID- 28690902
TI - Group A Streptococcal Pericarditis in a Four-Month-Old Infant: Case report.
AB - Purulent pericarditis is uncommon among paediatric patients and cases caused by
group A Streptococcus (GAS) are even rarer. We report a four-month-old female
infant who was referred to the Royal Hospital, Muscat, Oman, in 2015 with
pericardial effusion and cardiac tamponade. She had initially presented to a
secondary hospital with a two-week history of fever, a runny nose and shortness
of breath. Blood and pericardial fluid cultures confirmed GAS isolates. The
infant was treated with a two-week course of antibiotics and made a complete
recovery with no echocardiographical evidence of pericardial effusion at a two
month follow-up. To the best of the authors' knowledge, this case constitutes the
youngest infant to present with GAS pericarditis. As invasive GAS infections can
present in infancy, early recognition and treatment is required.
PMID- 28690903
TI - Mondor's Disease: Rare case of a painful breast lump in a middle-aged woman.
PMID- 28690904
TI - Auricular Pseudocyst Due to Unusual Repetitive Manipulation of the Ears: Clinical
approach.
PMID- 28690905
TI - Pseudoangiomatous Stromal Hyperplasia: A rare mimic of breast malignancy.
PMID- 28690906
TI - Long-Standing Asymptomatic Inguinoscrotal Hernia.
PMID- 28690907
TI - Corrigendum to "Docetaxel-Induced Systemic Sclerosis with Internal Organ
Involvement Masquerading as Congestive Heart Failure".
AB - [This corrects the article DOI: 10.1155/2017/4249157.].
PMID- 28690908
TI - Primary Occipital Ewing's Sarcoma with Subsequent Spinal Seeding.
AB - Ewing's sarcoma is a primary bone cancer that mainly affects the long bones. This
malignancy is particularly common in pediatric patients. Primary cranial
involvement accounts for 1% of cases, with occipital involvement considered
extremely rare. In this case study, primary occipital Ewing's sarcoma with a
posterior fossa mass and subsequent relapse resulting in spinal seeding is
reported. A 3-year-old patient presented with a 1-year history of left-sided
headaches, localized over the occipital bone with progressive torticollis.
Computed tomography (CT) imaging showed a mass in the left posterior fossa
compressing the brainstem. The patient then underwent surgical excision followed
by adjuvant chemoradiation therapy. Two years later, the patient presented with
severe lower back pain and urinary incontinence. Whole-spine magnetic resonance
imaging (MRI) showed cerebrospinal fluid (CSF) seeding from the L5 to the S4
vertebrae. Primary cranial Ewing's sarcoma is considered in the differential
diagnosis of children with extra-axial posterior fossa mass associated with
destructive permeative bone lesions. Although primary cranial Ewing's sarcoma
typically has good prognosis, our patient developed metastasis in the lower
spine. Therefore, with CNS Ewing's sarcoma, screening of the entire neural axis
should be taken into consideration for early detection of CSF seeding metastasis
in order to decrease the associated morbidity and mortality.
PMID- 28690909
TI - Congenital Infantile Fibrosarcoma Causing Intestinal Perforation in a Newborn.
AB - Congenital infantile fibrosarcoma (CIF) is a rare malignant mesenchymal tumor and
only 14 cases have been reported with gastrointestinal manifestation. We report
about a female newborn delivered per emergency cesarean section at 34 weeks of
gestation. Postnatally, she rapidly developed an acute abdomen and sonographic
evidence of intestinal perforation requiring laparotomy on the first day of life.
A perforated 2 * 3 cm sized spherical tumorous structure of the jejunum was
identified. Due to unknown histopathology at this point and unclear resectional
margins, she received a temporary ileostomy, which was closed two months later.
Histopathology revealed a congenital intestinal fibrosarcoma without the
characteristic ETV6-NTRK3 fusion transcript. In conclusion, this rare tumor must
be considered as differential diagnosis of intestinal perforations in newborns.
PMID- 28690910
TI - Modeling the causal regulatory network by integrating chromatin accessibility and
transcriptome data.
AB - Cell packs a lot of genetic and regulatory information through a structure known
as chromatin, i.e. DNA is wrapped around histone proteins and is tightly packed
in a remarkable way. To express a gene in a specific coding region, the chromatin
would open up and DNA loop may be formed by interacting enhancers and promoters.
Furthermore, the mediator and cohesion complexes, sequence-specific transcription
factors, and RNA polymerase II are recruited and work together to elaborately
regulate the expression level. It is in pressing need to understand how the
information, about when, where, and to what degree genes should be expressed, is
embedded into chromatin structure and gene regulatory elements. Thanks to large
consortia such as Encyclopedia of DNA Elements (ENCODE) and Roadmap Epigenomic
projects, extensive data on chromatin accessibility and transcript abundance are
available across many tissues and cell types. This rich data offer an exciting
opportunity to model the causal regulatory relationship. Here, we will review the
current experimental approaches, foundational data, computational problems,
interpretive frameworks, and integrative models that will enable the accurate
interpretation of regulatory landscape. Particularly, we will discuss the efforts
to organize, analyze, model, and integrate the DNA accessibility data,
transcriptional data, and functional genomic regions together. We believe that
these efforts will eventually help us understand the information flow within the
cell and will influence research directions across many fields.
PMID- 28690911
TI - Two-year clinical outcome of denosumab treatment alone and in combination with
teriparatide in Japanese treatment-naive postmenopausal osteoporotic women.
AB - This randomized prospective study aimed to evaluate the clinical outcome of
denosumab treatment alone and in combination with teriparatide in treatment-naive
postmenopausal Japanese female patients with osteoporosis. Thirty patients were
randomly assigned to two groups: (1) denosumab group (denosumab alone, n=13); and
(2) combination group (denosumab+teriparatide, n=17). Serum bone-specific
alkaline phosphatase (BAP), serum tartrate-resistant acid phosphatase (TRACP)-5b,
urinary cross-linked N-terminal telopeptides of type I collagen (NTX), and bone
mineral density (BMD) of L1-4 lumbar vertebrae (L-BMD) and bilateral total hips
(H-BMD) were determined at the first visit and at various time points up to 24
months post-treatment to determine percentage changes. Serum TRACP-5b and urinary
NTX were equally suppressed in both groups and maintained at low levels, with
slight increases at 12, 18 and 24 months. BAP was significantly decreased in both
groups from 4 to 24 months, with significant differences between the groups at 4,
8 and 15 months (P<0.05). L-BMD was significantly increased at most time points
in both groups, with a significant difference between the combination group and
denosumab group at 24 months (17.2% increase versus 9.6% increase; P<0.05). There
was no significant difference in H-BMD between the two groups, although the
levels tended to be higher in the combination group than in the denosumab group
(9.5% increase versus 5.6% increase). These findings suggest that
denosumab+teriparatide combination therapy may represent an important treatment
for primary osteoporotic patients at high risk of vertebral fracture.
PMID- 28690912
TI - Atypical skeletal manifestations of rickets in a familial hypocalciuric
hypercalcemia patient.
AB - Familial hypocalciuric hypercalcemia (FHH) is caused by inactivating mutations in
the calcium-sensing receptor (CaSR) gene. The loss of function of CaSR presents
with rickets as the predominant skeletal abnormality in mice, but is rarely
reported in humans. Here we report a case of a 16-year-old boy with FHH who
presented with skeletal manifestations of rickets. To identify the possible
pathogenic mutation, the patient was evaluated clinically, biochemically, and
radiographically. The patient and his family members were screened for genetic
mutations. Physical examination revealed a pigeon breast deformity and X-ray
examinations showed epiphyseal broadening, both of which indicate rickets.
Biochemical tests also showed increased parathyroid hormone (PTH), 1,25
dihydroxyvitamin D, and elevated ionized calcium. Based on these results, a
diagnosis of FHH was suspected. Sequence analysis of the patient's CaSR gene
revealed a new missense mutation (c.2279T>A) in exon 7, leading to the damaging
amino change (p.I760N) in the mature CaSR protein, confirming the diagnosis of
FHH. Moreover, the skeletal abnormities may be related to but not limited to
vitamin D abnormity. Elevated PTH levels and a rapid skeletal growth period in
adolescence may have also contributed. Our study revealed that rickets-like
features have a tendency to present atypically in FHH patients who have a mild
vitamin D deficiency, and that CaSR mutations may have a partial role in the
pathogenesis of skeletal deformities.
PMID- 28690914
TI - Investigation Of Obesity-Related Mortality Rates In Delaware.
AB - As Delaware's adult obesity crisis continues to be a leading public health
concern, we evaluated Delaware's 1999-2014 vital records to examine the
association between obesity and mortality. We used the Delaware population death
records from the Centers for Disease Control and Prevention (CDC) WONDER database
and the Delaware Health Statistics Center (DHSC). Together with the vital
records, we incorporated Microsoft Excel, SAS (Statistical Analysis System) and
GIS (geographic information system) tools to analyze obesity influences from
county residence, economic status, education, gender, and race. Using the 15-year
(1999-2014) time span with the CDC WONDER database, we observed a statistically
significant 28.7% increase in the age-adjusted Delaware obesity-related mortality
rates (where obesity was a contributory factor). Furthermore, obesity influenced
death counts in all three Delaware counties (New Castle, Kent, and Sussex). Kent
County experienced the largest increase (66.0%), followed by New Castle County
(47.4%), and Sussex County (25.2%). The DHSC mortality rates for all leading
causes of death from 2000 to 2011 indicated relatively stable mortality rates for
Delaware. However, using CDC WONDER data, the Delaware mortality rate for obesity
as a single underlying cause in 2011 was 56.9% higher than mortality rate in
2000.
PMID- 28690913
TI - Ghrelin, Amylin, Gastric Inhibitory Peptide and Cognition in Middle-Aged HIV
Infected and Uninfected Women: The Women's Interagency HIV Study.
AB - OBJECTIVE: To explore the gut-brain axis by examining gut hormone levels and
cognitive test scores in women with (HIV+) and without (HIV-) HIV infection.
DESIGN/METHODS: Participants included 356 women (248 HIV+, 108 at risk HIV-) in
the Brooklyn Women's Interagency HIV Study (WIHS) with measured levels of
ghrelin, amylin and gastric inhibitory peptide (GIP), also known as glucose
dependent insulinotropic polypeptide. Cross-sectional analyses using linear
regression models estimated the relationship between gut hormones and Trails A,
Trails B, Stroop interference time, Stroop word recall, Stroop color naming and
reading, and Symbol Digit Modalities Test (SDMT) with consideration for age, HIV
infection status, Wide Range Achievement Test score (WRAT), CD4 count, insulin
resistance, drug use, and race/ethnicity. RESULTS: Among women at mid-life with
chronic (at least 10 years) HIV infection or among those at risk, ghrelin, amylin
and GIP were differentially related to cognitive test performance by cognitive
domain. Better performance on cognitive tests was generally associated with
higher ghrelin, amylin and GIP levels. However, the strength of association
varied, as did significance level by HIV status. CONCLUSION: Previous analyses in
WIHS participants have suggested that higher BMI, waist, and WHR are associated
with better cognitive function among women at mid-life with HIV infection. This
study indicates that higher gut hormone levels are also associated with better
cognition. Gut hormones may provide additional mechanistic insights regarding the
association between obesity and Type 2 diabetes and cognition in middle-aged HIV+
and at risk HIV- women. In addition, measuring these hormones longitudinally
would add to the understanding of mechanisms of actions of these hormones and
their use as potential clinical tools for early identification and intervention
on cognitive decline in this vulnerable population.
PMID- 28690915
TI - Maintenance and Intensification of Bivalent Oral Poliovirus Vaccine Use Prior to
its Coordinated Global Cessation.
AB - OBJECTIVE: To examine the impact of different bivalent oral poliovirus vaccine
(bOPV) supplemental immunization activity (SIA) strategies on population immunity
to serotype 1 and 3 poliovirus transmission and circulating vaccine-derived
poliovirus (cVDPV) risks before and after globally-coordinated cessation of
serotype 1 and 3 oral poliovirus vaccine (OPV13 cessation). METHODS: We adapt
mathematical models that previously informed vaccine choices ahead of the
trivalent oral poliovirus vaccine to bOPV switch to estimate the population
immunity to serotype 1 and 3 poliovirus transmission needed at the time of OPV13
cessation to prevent subsequent cVDPV outbreaks. We then examine the impact of
different frequencies of SIAs using bOPV in high risk populations on population
immunity to serotype 1 and 3 transmission, on the risk of serotype 1 and 3 cVDPV
outbreaks, and on the vulnerability to any imported bOPV-related polioviruses.
RESULTS: Maintaining high population immunity to serotype 1 and 3 transmission
using bOPV SIAs significantly reduces 1) the risk of outbreaks due to imported
serotype 1 and 3 viruses, 2) the emergence of indigenous cVDPVs before or after
OPV13 cessation, and 3) the vulnerability to bOPV-related polioviruses in the
event of non-synchronous OPV13 cessation or inadvertent bOPV use after OPV13
cessation. CONCLUSION: Although some reduction in global SIA frequency can safely
occur, countries with suboptimal routine immunization coverage should each
continue to conduct at least one annual SIA with bOPV, preferably more, until
global OPV13 cessation. Preventing cVDPV risks after OPV13 cessation requires
investments in bOPV SIAs now through the time of OPV13 cessation.
PMID- 28690916
TI - Enhanced ferromagnetic resonance linewidth of the free layer in perpendicular
magnetic tunnel junctions.
AB - We report the frequency dependence of the ferromagnetic resonance linewidth of
the free layer in magnetic tunnel junctions with all perpendicular-to-the-plane
magnetized layers. While the magnetic-field-swept linewidth nominally shows a
linear growth with frequency in agreement with Gilbert damping, an additional
frequency-dependent linewidth broadening occurs that shows a strong asymmetry
between the absorption spectra for increasing- and decreasing external magnetic
field. Inhomogeneous magnetic fields produced during reversal of the reference
and pinned layer complex is demonstrated to be at the origin of the symmetry
breaking and the linewidth enhancement. Consequentially, this linewidth
enhancement provides indirect information on the magnetic coercivity of the
reference and pinned layers. These results have important implications for the
characterization of perpendicular magnetized magnetic random access memory bit
cells.
PMID- 28690917
TI - Factors affecting the body mass index, haemoglobin and serum ferritin level in
students.
AB - Ferritin is a protein found in reticuloendothelial system and does not work only
as a mid-size protein during Hemoglobin synthesis but also as storage protein for
iron delivery. This cross sectional study was conducted in District Shaheed
Benazirabad during the period of August 2015 to March 2016, for obtaining
credible and consolidated data. In present study we investigated BMI, Hb and S.f
level with relation to socioeconomic status in children and adults from total
2040 volunteers (girls n=991, boys n=1049). The questionnaire included education,
social class, age, sex, and information about dietary habits. Blood samples were
collected & assessed by ELISA method and sysmex hemoglobin auto analyzer
instrument for serum ferritin and hemoglobin level. The mean value of Body Mass
index, the average value of hemoglobin and serum ferritin level was observed
accordingly 18.6, 12.1 g/dl, 82.8 MUg/l in all samples. It was concluded that
monthly income of the volunteers have significant association with Hb, BMI and
Serum ferritin at the P<0.01 level. However, environmental conditions, blood loss
in females during menstruation, low maternal attention, socioeconomic and dietary
habits are main factors which affect the BMI, Hb and S.f level in students.
PMID- 28690918
TI - Erratum: Efficacy and safety of ClairYg(r), a ready-to-use intravenous
immunoglobulin, in adult patients with primary immune thrombocytopenia.
AB - [This corrects the article on p. 1 in vol. 7, PMID: 28203488.].
PMID- 28690919
TI - Plasma Membrane is Compartmentalized by a Self-Similar Cortical Actin Meshwork.
AB - A broad range of membrane proteins display anomalous diffusion on the cell
surface. Different methods provide evidence for obstructed subdiffusion and
diffusion on a fractal space, but the underlying structure inducing anomalous
diffusion has never been visualized because of experimental challenges. We
addressed this problem by imaging the cortical actin at high resolution while
simultaneously tracking individual membrane proteins in live mammalian cells. Our
data confirm that actin introduces barriers leading to compartmentalization of
the plasma membrane and that membrane proteins are transiently confined within
actin fences. Furthermore, superresolution imaging shows that the cortical actin
is organized into a self-similar meshwork. These results present a hierarchical
nanoscale picture of the plasma membrane.
PMID- 28690920
TI - Do Bradykinesia and Tremor Interfere in Voluntary Movement of Essential Tremor
Patients? Preliminary Findings.
AB - BACKGROUND: The aim of this study was to determine whether tremor and
bradykinesia impacted a dexterous activity performed by patients with essential
tremor (ET). METHODS: Core bradykinesia was assessed in 27 controls and 15
patients with ET using a rapid alternating movement (RAM) task. Then,
participants performed a "counting money" counting tasks while equipped with
inertial measurement units to detect and quantify tremor during movement. The
time required to perform subsections of the tasks and the rate of failure
(errors) were compared between groups using Mann-Whitney U tests and a chi-square
test, respectively. RESULTS: Patients with ET presented with significant
bradykinesia during the RAM task and had more tremor during the counting money
task. However, the time required to perform the task and rate of failure were
similar between groups. DISCUSSION: Results show that even though bradykinesia
was detected during fast movements, and that tremor was present during a task
requiring dexterity, both symptoms did not interfere with the performance of
patients with ET. This pilot study suggests that there may be a threshold at
which tremor will become problematic. Determining this threshold for a wide range
of daily activities may help determine when it is appropriate to initiate
treatment for patients with ET.
PMID- 28690921
TI - Risk Factors for Tremor in a Population of Patients with Severe Mental Illness:
An 18-year Prospective Study in a Geographically Representative Sample (The
Curacao Extrapyramidal Syndromes Study XI).
AB - BACKGROUND: The aim was to assess incidence, prevalence and risk factors of
medication-induced tremor in African-Caribbean patients with severe mental
illness (SMI). METHOD: A prospective study of SMI patients receiving care from
the only mental health service of the previous Dutch Antilles. Eight clinical
assessments, over 18 years, focused on movement disorders, medication use, and
resting tremor (RT) and (postural) action tremor (AT). Risk factors were modeled
with logistic regression for both current (having) tremor and for tremor at the
next time point (developing). The latter used a time-lagged design to assess
medication changes prior to a change in tremor state. RESULTS: Yearly tremor
incidence rate was 2.9% and mean tremor point prevalence was 18.4%. Over a third
of patients displayed tremor during the study. Of the patients, 5.2% had AT with
25% of cases persisting to the next time point, while 17.1% of patients had RT of
which 65.3% persisted. When tremor data were examined in individual patients,
they often had periods of tremor interspersed with periods of no tremor. Having
RT was associated with age (OR=1.07 per year; 95% confidence interval 1.03-1.11),
sex (OR=0.17 for males; 0.05-0.78), cocaine use (OR=10.53; 2.22-49.94),
dyskinesia (OR=0.90; 0.83-0.97), and bradykinesia (OR=1.16; 1.09-1.22).
Developing RT was strongly associated with previous measurement RT (OR=9.86; 3.80
25.63), with previous RT severity (OR=1.22; 1.05-1.41), and higher
anticholinergic load (OR= 1.24; 1.08-1.43). Having AT was associated with tremor
inducing medication (OR= 4.54; 1.90-10.86), cocaine use (OR=14.04; 2.38-82.96),
and bradykinesia (OR=1.07; 1.01-1.15). Developing AT was associated with,
previous AT severity (OR=2.62 per unit; 1.64-4.18) and tremor reducing medication
(OR=0.08; 0.01-0.55). CONCLUSIONS: Long-stay SMI patients are prone to developing
tremors, which show a relapsing-remitting course. Differentiation between RT and
AT is important as risk factors differ and they require different prevention and
treatment strategies.
PMID- 28690922
TI - Axial Sensory Tricks in Chorea-Acanthocytosis: Insights into Phenomenology.
AB - BACKGROUND: Trunk flexion and axial extension are characteristic symptoms of
chorea-acanthocytosis (ChAc). PHENOMENOLOGY SHOWN: A 41-year-old male with ChAc
(confirmed by VPS13A mutations) reported that his involuntary axial movements
were significantly ameliorated by either folding his arms over his chest or
putting his hands behind his head. EDUCATIONAL VALUE: These apparent "sensory
tricks" suggest a dystonic pathophysiology, and also merit further study to
analyze their potential for symptom control in ChAc.
PMID- 28690923
TI - Voxel Placement Precision for GABA-Edited Magnetic Resonance Spectroscopy.
AB - The purpose of the present study was to assess the reproducibility of voxel
placement for GABA-edited MRS. GABA-edited MRS data were acquired in 13 healthy
volunteers from (3 cm)3 voxel; and within the same session a second acquisition
was independently prescribed. A three-dimensional voxel mask image was
reconstructed in T1-image-space using the SVMask tool (in house software).
Reproducibility of voxel placement was assessed using the Dice overlap
coefficient, both within-subject and between-subject following co-registration of
T1 images and transformation of voxel mask images to standard space. Within
subject overlap coefficients were 86% +/- 5%. Between-subject overlap
coefficients were 75% +/- 10%. For the two voxel locations considered (occipital
and sensorimotor), voxel overlap was very similar. Between-subject values are
higher due to between-session effects, anatomical variability and volume mismatch
in standard space. While surprisingly low in terms of volume overlap, the overlap
coefficients correspond to acceptable linear displacements.
PMID- 28690924
TI - Zebrafish Models of Kidney Damage and Repair.
AB - The vertebrate kidney possesses the capacity to repair damaged nephrons, and this
potential is conserved regardless of the complexity of species-specific kidneys.
However, many aquatic vertebrates possess the ability to not only repair existing
nephrons, but also generate new nephrons after injury. Adult zebrafish have the
ability to recover from acute renal injury not only by replacing lost injured
epithelial cells of endogenous nephrons, but by also generating de novo nephrons.
This strong regeneration potential, along with other unique characteristics such
as the high degree of genetic conservation with humans, the ease of harvesting
externally fertilized, transparent embryos, the accessibility to larval and adult
kidneys, and the ability to perform whole organism phenotypic small molecule
screens, has positioned zebrafish as a unique vertebrate model to study kidney
injury. In this review, we provide an overview of the contribution of zebrafish
larvae/adult studies to the understanding of renal regeneration, diseases, and
therapeutic discovery.
PMID- 28690925
TI - The Role of PTSD, Depression, and Alcohol Misuse Symptom Severity in Linking
Deployment Stressor Exposure and Post-Military Work and Family Outcomes in Male
and Female Veterans.
AB - Exposure to stressors during military deployment puts veterans at risk for
reduced post-military quality of life. Stress-related mental health problems may
lead to decreased well-being within work and family domains, yet few studies have
explored associations in the context of gender. We examined relationships between
deployment stressors and post-military functioning and satisfaction in the
domains of work and family, with a focus on PTSD, depression, and alcohol misuse
symptomatology as potential mediators. Participants included 522 male and female
Iraq and Afghanistan War veterans assessed longitudinally. Structural equation
models supported several direct and indirect pathways linking deployment
stressors to work and family outcomes for both men and women. PTSD had an
important role in these associations. Depression also played a significant role,
particularly for women. These findings build on prior research by elucidating
potential gender-specific risk, which may be applied to better tailor services to
veterans' unique needs.
PMID- 28690926
TI - Razanandrongobe sakalavae, a gigantic mesoeucrocodylian from the Middle Jurassic
of Madagascar, is the oldest known notosuchian.
AB - Razanandrongobe sakalavae Maganuco, Dal Sasso & Pasini, 2006 is a large predatory
archosaur from the Middle Jurassic (Bathonian) of the Mahajanga Basin, NW
Madagascar. It was diagnosed on the basis of teeth and a fragmentary maxilla, but
its affinities were uncertain. Here we describe new cranial remains (above all,
an almost complete right premaxilla and a caudally incomplete left dentary) that
greatly improve our knowledge on this enigmatic species and reveal its anatomy to
be crocodylomorph. The right premaxilla indicates that the rostrum was deep,
wide, and not pointed; it bears five teeth that are sub-vertical and just
slightly curved lingually; the mesial teeth are U-shaped in cross-section and
have serrated carinae on the lingual side; the aperturae nasi osseae (external
bony nares) are confluent and face rostrally; and there is no lateral groove at
the premaxillomaxillary suture for reception of a hypertrophied lower caniniform
tooth. The preserved portion of the left dentary has an edentulous tip and bears
eight large mandibular teeth of which the mesial (1-3) are the largest, but none
is a hypertrophied caniniform tooth; the mandibular (dentary) symphysis extends
caudally to the level of the third tooth; the splenial is not preserved, but its
sutural marks on the dentary indicate that it contributed to the mandibular
symphysis for at least 20% of the symphyseal length in dorsal aspect. On the
basis of this new data, some previously uncertain features of the holotype
maxilla-such as the margin of the suborbital fenestra, the contact surfaces for
the palatine, the ectopterygoid, and the jugal-are now apparent. Testing of the
phylogenetic position of the species within Crocodylomorpha indicates that R.
sakalavae is a mesoeucrocodylian. It also represents one of the earliest events
of exacerbated increase in body size along the evolutionary history of the group.
In addition, it is by far the oldest notosuchian. A cranial reconstruction of
this gigantic predator is also attempted here. The very robust jaw bones of R.
sakalavae, coupled with its peculiar dentition, strongly suggest a diet that
included hard tissue such as bone and tendon.
PMID- 28690927
TI - Quantitative proteome-level analysis of paulownia witches' broom disease with
methyl methane sulfonate assistance reveals diverse metabolic changes during the
infection and recovery processes.
AB - Paulownia witches' broom (PaWB) disease caused by phytoplasma is a fatal disease
that leads to considerable economic losses. Although there are a few reports
describing studies of PaWB pathogenesis, the molecular mechanisms underlying
phytoplasma pathogenicity in Paulownia trees remain uncharacterized. In this
study, after building a transcriptome database containing 67,177 sequences, we
used isobaric tags for relative and absolute quantification (iTRAQ) to quantify
and analyze the proteome-level changes among healthy P. fortunei (PF), PaWB
infected P. fortunei (PFI), and PaWB-infected P. fortunei treated with 20 mg L-1
or 60 mg L-1 methyl methane sulfonate (MMS) (PFI-20 and PFI-60, respectively). A
total of 2,358 proteins were identified. We investigated the proteins profiles in
PF vs. PFI (infected process) and PFI-20 vs. PFI-60 (recovered process), and
further found that many of the MMS-response proteins mapped to "photosynthesis"
and "ribosome" pathways. Based on our comparison scheme, 36 PaWB-related proteins
were revealed. Among them, 32 proteins were classified into three functional
groups: (1) carbohydrate and energy metabolism, (2) protein synthesis and
degradation, and (3) stress resistance. We then investigated the PaWB-related
proteins involved in the infected and recovered processes, and discovered that
carbohydrate and energy metabolism was inhibited, and protein synthesis and
degradation decreased, as the plant responded to PaWB. Our observations may be
useful for characterizing the proteome-level changes that occur at different
stages of PaWB disease. The data generated in this study may serve as a valuable
resource for elucidating the pathogenesis of PaWB disease during phytoplasma
infection and recovery stages.
PMID- 28690928
TI - The smell of environmental change: Using floral scent to explain shifts in
pollinator attraction.
AB - As diverse environmental changes continue to influence the structure and function
of plant-pollinator interactions across spatial and temporal scales, we will need
to enlist numerous approaches to understand these changes. Quantitative
examination of floral volatile organic compounds (VOCs) is one approach that is
gaining popularity, and recent work suggests that floral VOCs hold substantial
promise for better understanding and predicting the effects of environmental
change on plant-pollinator interactions. Until recently, few ecologists were
employing chemical approaches to investigate mechanisms by which components of
environmental change may disrupt these essential mutualisms. In an attempt to
make these approaches more accessible, we summarize the main field, laboratory,
and statistical methods involved in capturing, quantifying, and analyzing floral
VOCs in the context of changing environments. We also highlight some outstanding
questions that we consider to be highly relevant to making progress in this
field.
PMID- 28690929
TI - Applying pollen DNA metabarcoding to the study of plant-pollinator interactions.
AB - PREMISE OF THE STUDY: To study pollination networks in a changing environment, we
need accurate, high-throughput methods. Previous studies have shown that more
highly resolved networks can be constructed by studying pollen loads taken from
bees, relative to field observations. DNA metabarcoding potentially allows for
faster and finer-scale taxonomic resolution of pollen compared to traditional
approaches (e.g., light microscopy), but has not been applied to pollination
networks. METHODS: We sampled pollen from 38 bee species collected in Florida
from sites differing in forest management. We isolated DNA from pollen mixtures
and sequenced rbcL and ITS2 gene regions from all mixtures in a single run on the
Illumina MiSeq platform. We identified species from sequence data using
comprehensive rbcL and ITS2 databases. RESULTS: We successfully built a proof-of
concept quantitative pollination network using pollen metabarcoding. DISCUSSION:
Our work underscores that pollen metabarcoding is not quantitative but that
quantitative networks can be constructed based on the number of interacting
individuals. Due to the frequency of contamination and false positive reads,
isolation and PCR negative controls should be used in every reaction. DNA
metabarcoding has advantages in efficiency and resolution over microscopic
identification of pollen, and we expect that it will have broad utility for
future studies of plant-pollinator interactions.
PMID- 28690930
TI - Plant-pollinator interactions under climate change: The use of spatial and
temporal transplants.
AB - Climate change is affecting both the timing of life history events and the
spatial distributions of many species, including plants and pollinators. Shifts
in phenology and range affect not only individual plant and pollinator species
but also interactions among them, with possible negative consequences for both
parties due to unfavorable abiotic conditions or mismatches caused by differences
in shift magnitude or direction. Ultimately, population extinctions and
reductions in pollination services could occur as a result of these climate
change-induced shifts, or plants and pollinators could be buffered by plastic or
genetic responses or novel interactions. Either scenario will likely involve
altered selection pressures, making an understanding of plasticity and local
adaptation in space and time especially important. In this review, we discuss two
methods for studying plant-pollinator interactions under climate change: spatial
and temporal transplants, both of which offer insight into whether plants and
pollinators will be able to adapt to novel conditions. We discuss the advantages
and limitations of each method and the future possibilities for this area of
study. We advocate for consideration of how joint shifts in both dimensions might
affect plant-pollinator interactions and point to key insights that can be gained
with experimental transplants.
PMID- 28690931
TI - Nectar sampling for prairie and oak savanna butterfly restoration.
AB - PREMISE OF THE STUDY: Understanding floral resources is vital for restoring
pollinators in habitats affected by anthropogenic development and climate change.
As the primary adult food, nectar can limit butterfly longevity and reproduction.
For pollinator restoration, it would therefore be useful to examine nectar
resources. However, because many flowers preferred by butterflies are too small
for microcapillary sampling and the potential for nectar contamination can make
accurate measurement difficult, we developed a modified centrifugation method to
extract and separate nectar and pollen. METHODS: We sampled nectar from 19 forbs
using a glass wool filter to exclude potentially contaminating pollen during
centrifugation. To minimize costs, we measured sugar concentration by
refractometry and simple ninhydrin tests for amino acids and improved test
accuracy by subsequent image analysis. Artificial nectars were used to verify the
new techniques. RESULTS: This method eliminated pollen from samples, while only
slightly increasing sugar concentrations. Some amino acids were lost during
centrifugation, but only samples with high concentrations exhibited substantial
loss. We found significant differences in nectar quality among species, as well
as an unexpected inverse relationship between amino acid and sugar
concentrations. DISCUSSION: This modified centrifugation technique is an
efficient, less damaging, inexpensive approach for collecting nectar from small
flowers while eliminating pollen contamination, and will facilitate restoration
of declining pollinators and thereby the plants they service.
PMID- 28690932
TI - An assessment of the efficacy and peak catch rates of emergence tents for
measuring bee nesting.
AB - PREMISE OF THE STUDY: Emergence tents are a new tool used to understand nesting
ecology of ground nesting bee species. However, many questions remain about how
to use tents effectively. We assessed (a) variance in tent capture rates over
time, (b) the effects of site characteristics on proportion of tents capturing
bees, and (c) the effect of soil characteristics on nest site choice. METHODS:
Emergence tents were placed out for one week in May, June, and August and checked
daily. Soil, bee, and floral characteristics were recorded. RESULTS: Across all
sites and months the average number of tents capturing bees was less than 20%
during one week of sampling, but this varied between sites. Tent captures
decreased after 48 h deployment, but accumulation differed seasonally, with
slower accumulation of total bees caught in May than in June or August. Although
capture rates were not affected by bee or floral abundance, soil moisture beneath
a tent influenced where bees were captured. DISCUSSION: Effective use of
emergence tents may require adjusting the length of deployment depending on
season and will require a minimum of 48 h installation to help maximize efficacy.
The overall low capture rates demonstrate the need to optimize emergence tent
use.
PMID- 28690933
TI - Studying plant-pollinator interactions in a changing climate: A review of
approaches.
AB - Plant-pollinator interactions are potentially at risk due to climate change.
Because of the spatial and temporal variation associated with the effects of
climate change and the responses of both actors, research to assess this
interaction requires creative approaches. This review focuses on assessments of
plants' and pollinators' altered phenology in response to environmental changes,
as phenology is one of the key responses. I reviewed research methods with the
goal of presenting the wide diversity of available techniques for addressing
changes in these interactions. Approaches ranged from use of historical specimens
to multisite experimental community studies; while differing in depth of
historical information and community interactions, all contribute to assessment
of phenology changes. Particularly insightful were those studies that directly
assessed the environmental changes across spatial and temporal scales and the
responses of plants and pollinators at these scales. Longer-term studies across
environmental gradients, potentially with reciprocal transplants, enable an
assessment of climate impacts at both scales. While changes in phenology are well
studied, the impacts of phenology changes are not. Future research should include
approaches to address this gap.
PMID- 28690934
TI - Studying plant-pollinator interactions facing climate change and changing
environments.
AB - Plant-pollinator interactions are essential for successful plant reproduction in
both natural and agricultural systems. These interactions are negatively impacted
by recent large-scale alterations of the environments, particularly climate
change. The responses of plants and pollinators to changing abiotic conditions
that vary seasonally and geographically are often uncoordinated, potentially
leading to the breakdown of this interaction. The complexity of the responses of
plants and pollinators to our changing climate necessitates creative approaches.
The six articles in this special issue directly address this need by providing a
variety of key methods and reviews of current methodology. The articles include:
DNA barcoding methods for use on pollen collected from visiting bees; methods for
assessment of plant attraction traits (nectar and review of floral volatiles
methods); a field sampling method for ground nesting bees; a review of using
spatial and temporal transplants for addressing changing dynamics of plant
pollinator interactions; and a review of approaches used to assess potential
shifts in phenology of plants and pollinators. Collectively, these articles
illustrate some of the breadth of approaches needed to address the changing
dynamics of plant-pollinator interactions.
PMID- 28690935
TI - Acoustic Radiation Force Impulse Imaging in Benign and Malignant Breast Lesions.
AB - BACKGROUND: Elastography is a promising way to assess tissue differences
regarding stiffness or elasticity, which has been historically assessed manually
by palpation. Combined with conventional imaging modalities, shear wave
elastography can potentially evaluate the stiffness of a breast lesion and
consequently help detect malignant breast tumor from benign ones. The aim of this
study was to evaluate the diagnostic role of shear wave elastography in breast
lesions in the Indian population. MATERIAL AND METHODS: Fifty patients presenting
with breast lesions were included in the study. All the patients were subjected
to B-mode ultrasound and elastography using shear wave with Virtual Touch Imaging
(VTITM) (Siemens Medical Solutions USA, Inc., PA, USA) and Virtual Touch
Quantification (VTQTM) (Siemens Medical Solutions USA, Inc., PA, USA) and the
obtained data was analyzed using an appropriate statistical test (independent
samples t-test). RESULTS: In our study group of 50 patients, 34 were benign and
16 were malignant. VTITM showed a sensitivity of 97% and a specificity of 93%
with a positive predictive value (PPV) of 97% for benign lesions. VTITM showed a
sensitivity of 87.5 % and a specificity of 100% with a PPV of 100% for malignant
lesions. VTQTM showed a sensitivity of 71.4% and a specificity of 100% with a PPV
of 100% for benign lesions. VTQTM showed a sensitivity of 100% and a specificity
of 100% with a PPV of 76.6% for malignant lesions. CONCLUSIONS: VTITM was more
reliable as a diagnostic tool compared to VTQTM in benign lesions and both are
equally reliable in identifying malignant lesions. Acoustic radiation force
impulse (ARFI) plays a significant role as an adjuvant diagnostic tool to B-mode
imaging for assessing breast lesions.
PMID- 28690936
TI - A Case of Imatinib-Induced Hepatitis.
AB - A 71-year-old female with a past medical history of Philadelphia chromosome
positive chronic myelogenous leukemia on imatinib therapy, Sjogren's syndrome,
and hypothyroidism presents with acute hepatitis. After a comprehensive workup
ruling out viral, infectious and metabolic etiologies imatinib is stopped which
results in immediate improvement. The biopsy is consistent with drug-induced
liver damage; the patient is started on oral prednisone and discharged.
Unfortunately, our patient's liver function does not improve over the course of
the next week and she is readmitted for hepatic and renal failure. During this
second admission patient's condition continues to deteriorate with concomitant
gastric bleeding, renal injury, and cellulitis. She ultimately chooses a
palliative approach.
PMID- 28690937
TI - An Unusual Case of Aortic Stenosis in Systemic Sclerosis.
AB - Systemic sclerosis is a connective tissue disorder that frequently involves the
heart. All cardiac structures can be involved but aortic valve involvement is
rare. We report a case of an 83-year-old man with a history of systemic sclerosis
presenting with shortness of breath. A transthoracic echocardiogram revealed
severe aortic stenosis that could not be explained by other causes. These
patients often pose challenges in management as they are not surgical candidates.
Transaortic valvular implantation is a viable option for these patients.
PMID- 28690938
TI - Alexia Without Agraphia: A Rare Entity.
AB - Pure alexia refers to an acquired disorder associated with the damage to medial
occipitotemporal gyrus in the dominant hemisphere, which is also known as visual
word form area (VWFA). VWFA is involved in rapid word recognition and fluent
reading. Alexia without agraphia is a disconnection syndrome that occurs when the
splenium is also damaged with the occipital lobe on a dominant side. We report a
case of a 72-year-old right-handed male who presented with alexia without
agraphia accompanied by right homonymous hemianopia resulting from acute infarct
of the left occipital lobe, the splenium of the corpus callosum and posterior
thalamus that probably occurred on the previous day. During the evaluation, he
exhibited marked impairment in the ability to read with the vision being grossly
normal. Magnetic resonant imaging (MRI) revealed an acute infarct of the left
occipital lobe, the splenium of the corpus callosum and posterior thalamus. A
computerized tomography angiogram (CTA) revealed left posterior cerebral artery
(PCA) territory infarct without any evidence of hemorrhagic conversion.
Infarction of the occipital lobe on the dominant side (left) in a right-handed
individual may cause a disruption in the visual word form area and is manifested
by an inability to read with no abnormalities in visual acuity.
PMID- 28690939
TI - Central Diabetes Insipidus and Hyperglycemic Hyperosmolar State Following
Accidental Carbon Monoxide Poisoning.
AB - Carbon monoxide poisoning is common and carries significant morbidity and
mortality. The nervous system, particularly the brain, is frequently affected by
it, owing to its high metabolic activity and oxygen requirements. Carbon monoxide
damages the nervous system by both hypoxic and inflammatory mechanisms. Central
diabetes insipidus is an extremely rare complication of carbon monoxide
poisoning. Herein, we report the case of a young lady, who developed this
complication and severe hypernatremia after accidental carbon monoxide poisoning.
She also developed a hyperglycemic hyperosmolar state during the treatment for
hypernatremia. To the best of our knowledge, both these entities have not been
reported together in association with carbon monoxide poisoning. The purpose of
this article is to emphasize the anticipation and early recognition of central
diabetes insipidus in carbon monoxide poisoning. This can prevent severe
hypernatremia and complications associated with its presence and treatment.
PMID- 28690940
TI - Simultaneous Robot-assisted Laparoscopic Excision of Pre-pyloric Gastrointestinal
Stromal Tumor and Cholecystectomy.
AB - Operating on more than a single procedure in a same surgical intervention saves
time, anesthesia duration and can increase the overall quality of life by
lowering the duration of hospital stay and minimizing patient anxiety. But such
interventions require expertise, high surgical performance, and precision in
anatomical manipulation. We present a case of an outstanding performance of a
unique minimally invasive simultaneous approach of removing a pre-pyloric
gastrointestinal stromal tumor (GIST) along with a cholecystectomy by a robot
assisted laparascopic surgical system. So far, only 33 cases of GIST have been
reported in literature that were managed by robot-assistance, and this case is
the first of its kind. This is the case of a 60-year-old overweight female who
presented for a follow-up for chest discomfort, shortness of breath, chronic
gastric reflux and classical features of cholecystitis along with diarrheal and
constipation episodes. A gastroduodenoscopy showed a mass in the pre-pyloric area
that extended in the luminal cavity. A robot-assisted laparascopic approach was
planned, and with precision and surgical expertise the mass was removed along
with a cholecystectomy. The surgical specimen were confirmed on histopathology.
PMID- 28690941
TI - A Simulation-based Quality Improvement Approach to Improve Pediatric Resident
Competency with Required Procedures.
AB - INTRODUCTION: Pediatric residents report a lack of confidence and competence with
procedural skills at graduation. Training programs could benefit from improved
approaches to target these needs. Using the Institute for Healthcare Improvement
(IHI) Model for Improvement and three Plan-Do-Study-Act (PDSA) cycles, we
examined the impact of a procedure simulation boot camp on self-reported
procedural confidence and competence as well as the longitudinal impacts of these
sequential interventions on Accreditation Council for Graduate Medical Education
(ACGME) Graduating Resident Survey (GRS) results. METHODS: Three rapid cycle
interventions were performed in successive academic years. The interventions
included 1) increased awareness of available procedural experiences, 2)
institution of procedural educational conferences, and 3) implementation of a
senior resident procedure boot camp. Senior resident self-reported procedural
confidence was measured before and after the boot camp. Procedural competence was
measured using the ACGME GRS. Results: Thirty-two of 34 senior residents (94%)
completed the 2016 ACGME GRS, similar to the response rates of 2014 (92%) and
2015 (94%), and 30 of 34 third-year residents participated in the procedure boot
camp (88%). Resident confidence and competence with procedural skills improved
after the institution of the quality improvement intervention. ACGME GRS-reported
competency increased in bag and mask ventilation (77% to 94%), neonatal
endotracheal intubation (39% to 69%), peripheral IV placement (10% to 50%), and
umbilical catheter placement (35% to 53%). CONCLUSION: A quality improvement
intervention with three rapid PDSA cycles was successful in improving senior
pediatric resident confidence and competence with ACGME required procedural
skills.
PMID- 28690942
TI - Cardiac Arrhythmias Resulting from a Peripherally Inserted Central Catheter: Two
Cases and a Review of the Literature.
AB - We present two cases of patients being treated for diabetic ketoacidosis in the
intensive care unit who experienced cardiac arrhythmia secondary to peripherally
inserted central catheters (PICCs). In one instance, the patient became
bradycardic and experienced related loss of consciousness, ultimately requiring
cardiopulmonary resuscitation. In the second case, the patient experienced an
episode of nonsustained ventricular tachycardia. We explore the various types of
arrhythmias that have been reported secondary to central venous catheters, as
well as factors that place patients at an increased risk for arrhythmia while
undergoing PICC insertion. Furthermore, we look at the literature for methods to
improve the insertion of PICC lines by decreasing the risk of catheter over
insertion as well as the effects of training for PICC placement.
PMID- 28690943
TI - Transradial vs. Transfemoral Approach in Cardiac Catheterization: A Literature
Review.
AB - The main objective of this review paper is to study the comparison between
transradial and transfemoral approach in catheterization. Transradial and
transfemoral are two main approaches which are used as a diagnostic and
therapeutic purpose in catheterization. The transradial approach in
interventional cardiology is safe, effective, and feasible as compared to the
transfemoral approach. The aim of this study is to compare pros and cons of
transradial vs. transfemoral approach in catheterization. We conducted this
systematic review on the role of transradial vs. transfemoral catheterization.
The articles included real human data on interventional approaches. Reviews on
these strategies were conducted in PubMed, medical literature analysis and
retrieval system online (MEDLINE), Cochrane, Medscape and National Institute of
Health. To maintain a high standard of review, studies published in all non
famous journals were excluded. Data collected from the studies have suggested
that transradial approach has less bleeding complications, cost effective,
decreased hospital mortality rate, and less access site complications as compared
to transfemoral approach. However, longer procedural duration and radiation
exposure are still concerns regarding transradial approach. The findings of the
present study show that transradial approach in catheterization is safe,
effective, and feasible as compared to the transfemoral approach. However,
duration and radiation exposure are higher in the transradial access. Several
studies suggest that the modern approach overweight in benefits with the
comparison to the classical approach.
PMID- 28690944
TI - Acute Inflammatory Demyelinating Polyneuroradiculopathy with Ipilimumab in
Metastatic Melanoma: A Case Report and Review of Literature.
AB - Ipilimumab (Bristol-Myers Squibb Co., New York, NY) is a novel anticancer
medication used for the treatment of metastatic melanoma. The exact mechanism of
its action remains unclear; however, data from previous clinical trials
postulates the immunomodulatory activity of ipilimumab to enhance therapeutic
effectiveness. Ipilimumab was approved by the Food and Drug Administration (FDA)
in March 2011 for use in stage III and IV of unresectable metastatic melanoma. We
report a single case of acute inflammatory demyelinating polyneuroradiculopthy
(AIDP) in the patient treated with ipilimumab for recurrent metastatic melanoma.
The patient presented with multiple falls that started after the third infusion
of ipilimumab. Other symptoms were hoarseness of voice, motor deficits in his
right arms, and tingling in both hands. The deficits progressed into near
complete loss of movement and sensation in all four extremities over the course
of two weeks. However, his bladder and bowel functions were intact. There was no
history of fever, recent travel, exposure to sick contacts, insect bites, or
gastrointestinal symptoms. Along with strong immune-mediated pharmacological
response towards cancer cells, ipilimumab also induces immune-related adverse
events (irAEs) within normal tissues by the mechanism of molecular mimicry.
PMID- 28690945
TI - Pacemaker Placement in Persistent Left Superior Vena Cava.
AB - Persistent left superior vena cava (PLSVC) is a rare disorder which is
asymptomatic and hence is usually discovered while performing interventions
through the left subclavian vein. We present a case of a 78-year-old male who was
undergoing elective placement of a permanent pacemaker for tachycardia -
bradycardia syndrome with post-conversion pauses of up to nine seconds. After
achieving access through the left subclavian vein the wire kept on going on the
left side of the chest instead of crossing the midline to the right side. The
wire was removed and contrast venography was done, PLSVC with dilated coronary
sinus emptying into the right atrium was confirmed. There was some difficulty in
passing the lead to the right ventricle even with the acute curve in the stylet.
The sheath size was increased and a longer deflectable sheath was used and with
the tip of the lead anteriorly the right ventricle was cannulated and the lead
was affixed. There were good sensing and pacing parameters. Post procedure chest
x-ray was done and the patient was discharged without any complications.
PMID- 28690946
TI - A Rare Case of Double-Headed Psoas Minor Muscle with Review of its Known
Variants.
AB - Variations of the muscles of humans are important to remember for those who
interpret imaging and for those who operate near these anomalies. Herein, we
describe a rare two-headed psoas minor muscle found incidentally during
dissection of the posterior abdominal wall. This case is presented with a
detailed review of all known variations of the minor psoas and is analyzed
through a literature review.
PMID- 28690947
TI - Autoamputation and Polyneuropathy in Mixed Connective Tissue Disorder: A Case
Report.
AB - Mixed connective tissue disorder (MCTD) is a multisystem disease with overlapping
features of other autoimmune diseases, such as systemic lupus erythematosus
(SLE), myositis, rheumatoid arthritis, and scleroderma. MCTD presents with a
distinctive antibody in serum known as U1-ribonucleoprotein (RNP). MCTD is quite
rare as compared to other connective tissue disorders like SLE, systemic
sclerosis, dermatomyositis, and polymyositis. We describe a case of MCTD in a
young Asian female of 30 year old. This case highlights rare co-existence of
polyneuropathy and autoamputation in MCTD disorder. Trigeminal neuralgia and
cranial nerve involvements have been previously reported in MCTD but the findings
of polyneuropathy and autoamputation are extremely rare.
PMID- 28690948
TI - Pineal Gland Agenesis: Review and Case Illustration.
AB - Agenesis of the pineal gland has rarely been reported in the medical literature.
Herein, we report a cadaveric specimen found to have agenesis of the pineal
gland. The remaining gross examination of the brain was normal. A review of the
literature was performed on this unusual finding.
PMID- 28690950
TI - The Role of Parents' Literacy in Malnutrition of Children Under the Age of Five
Years in a Semi-Urban Community of Pakistan: A Case-Control Study.
AB - OBJECTIVES: According to a recent survey, Pakistan was ranked as the third
highest country with malnutrition and the under-five child mortality. No
realistic solution for this growing problem has been found despite the fact that
the struggle to tackle the issue of malnutrition among young Pakistani children
has been going on for the last several decades. The objective of our study was to
look into the relationship between parental education and malnutrition in
Pakistan and to make a recommendation to improve the nutritional condition of the
children. METHOD: We carried a case-control study among 400 mothers from February
2016 to July 2016 in a primary health care center located in a peri-urban
community in Pakistan. A self-constructed questionnaire comprising of 75
questions was used to collect the data. RESULTS: The mean age of mother was found
to be 27.61 +/- 5.130. The majority of the mothers were uneducated 168 (42.0%)
while only 116 (29.0%) fathers were uneducated. About 226 (56.5%) of the children
had a normal nutritional status while 102 (25.5%) had first-degree malnutrition,
52 (13.0%) had second-degree malnutrition, and 20 (5.0%) had a third-degree
malnutrition. Higher paternal educational status (p = 0.008) and maternal
educational status (p = 0.011) were found to be significantly associated with
normal child nutritional status. CONCLUSION: It is recommended that the education
of parents, especially females, in the rural and semi-urban areas should be
promoted and given due importance. The focus of all these programs should be the
mother in terms of security, employment, literacy, justice, healthcare, food,
shelter, and social equality.
PMID- 28690949
TI - Role of Sex Hormone Levels and Psychological Stress in the Pathogenesis of
Autoimmune Diseases.
AB - The aim of this review article is to assess the connection between psychological
stress and sex hormones and their effect on the development of autoimmune
diseases. Psychological stress describes what people feel when they are under
mental, physical, or emotional pressure. We searched for online articles using
MEDLINE(r), Embase, Cochrane Library and Google Scholar. Our research yielded a
total of 165 articles out of which 30 articles were considered for further
perusal. The articles were reviewed from February 2016 to February 2017. Case
reports and patients suffering from hematolymphoid malignancies and active
infections were excluded from the review. Estrogen and testosterone are potential
physiological regulatory factors for the peripheral development of CD4+CD25+ T
regulatory cells. Stress at any age leads to the depletion of estrogen and
testosterone stores in the body, leading to the loss of expansion of T regulatory
cells, making the immature B cells evade the negative selection at the germinal
center, or in other words, leading to the loss of central tolerance, a triggering
event in autoimmune diseases like systemic lupus erythematosus. Autoimmune
diseases in women are most likely due to changes in estrogen levels during
mental, physical, pre-menopausal, post-menopausal, and pregnancy-induced stress.
We conclude that modulating estrogen in females (pre-menopausal and post
menopausal) and testosterone in males can be used to treat stress-related immune
imbalance resulting in autoimmune diseases in both sexes.
PMID- 28690951
TI - Coronary Artery Bypass Graft in a Young Man.
AB - Currently, there are no explicit guidelines on the management of acute myocardial
infarction (MI) in young adults under the age of 30. The lack of published
literature to guide clinicians in the care of young adults with MI has prompted
us to report a case exemplary for the successful treatment with coronary artery
bypass graft (CABG). A 25-year-old man developed acute MI and underwent on-pump
five quintuple CABG using bilateral internal mammary arteries and left greater
saphenous vein. This appropriate and timely intervention may have helped to
prevent cardiac death and maintain the quality of life.
PMID- 28690952
TI - Targeted Radiofrequency Ablation as an Adjunct in Treatment of Lumbar Facet
Cysts.
AB - Lumbar facet cysts are frequently found in patients with facet degeneration and
segmental instability. When the facet cyst is localized in the neural foramina
and lateral recess or becomes large, it can cause radiculopathy or neurogenic
claudication. These symptomatic cysts are typically treated interventionally with
drainage and a corticosteroid injection or attempts via overinflation to rupture
the cyst; however, these procedures have a significant recurrence rate (up to
50%) and often need to be repeated or lead to lumbar surgery if unsuccessful.
This is the first report of using targeted radiofrequency (RF) current as an
adjunct to cyst drainage. Although RF has been used for years to treat facet pain
indirectly by targeting the medial facet nerve branches, with this technique,
under image guidance, the actual cyst is percutaneously drained and then
cauterized along with the associated facet capsule, where the original cyst
developed. This has improved overall results with less cyst recurrence than
previous percutaneous methods and was documented with both intermediate and long
term followup clinically and with magnetic resonance imaging (MRI) scans. This
report reviews the underlying anatomy and pathology of the facet joint relating
to the development of facet cysts and how current percutaneous treatments for
lumbar facet cysts can be supplemented and improved by adding targeted RF
ablation to the percutaneous options available to treat a lumbar facet cyst.
PMID- 28690953
TI - Venous Diversion Surgery Revisited: A Baffling Situation.
AB - With the increasing number of survivors with congenital heart disease (CHD)
reaching adulthood, it is important for the clinician to be familiar with the
various surgical options performed in this growing patient population. We
describe the case of a 65-year-old female who presented with hypoxia and right-to
left shunting following a surgical repair of an atrial septal defect (ASD)
secundum and anomalous pulmonary veins with a partial atrial diversion procedure
in childhood. The use of multimodality cardiovascular imaging using
echocardiography, computed tomography, magnetic resonance imaging, and invasive
cardiac catheterization was complementary in the preoperative diagnosis and
management of this unique baffling situation.
PMID- 28690954
TI - Delay in the Diagnosis of Adult-Onset Still's Disease.
AB - Adult-onset Still's disease (AOSD) is a systemic autoinflammatory disease
characterized by symptoms including spiking fever, arthralgia, myalgia,
maculopapular rash, and pharyngitis. The lack of diagnostic biomarker, non
specific clinical presentation, and the rarity of AOSD often result in a
significant delay in diagnosis and treatment. While the average time of initial
presentation to diagnosis is four months, we present a case of AOSD diagnosis
three years after initial onset of classical symptoms. By reporting the case of
delayed diagnosis for AOSD, we hope to raise awareness in our medical community
about the diagnostic difficulty in AOSD. The present case describes an otherwise
healthy male who presented with typical symptoms of AOSD, but the diagnosis of
AOSD was missed during his first presentation. In the second flaring episode, the
diagnosis of AOSD was established. He had an excellent therapeutic response to
anakinra and prednisone during the acute flaring episode. He is currently in
complete remission on methotrexate as maintenance therapy.
PMID- 28690955
TI - Energy Drinks and the Risk of Cardiovascular Disease: A Review of Current
Literature.
AB - Energy drinks (EDs) are commonly used as a dietary supplement by young
adolescents and adults. They are often used as a source of energy in order to
enhance physical and mental performance. EDs contain a variety of substances, but
caffeine is the main component. Safety has been the biggest concern associated
with consuming EDs. Case reports, observational studies, and meta-analyses have
been done in order to determine the effects of EDs on cardiovascular changes. The
detrimental effects of EDs are cardiac arrhythmias, myocardial infarction,
prolonged QT interval, aortic dissection, and death. In this article, we review
case reports, observational studies, and meta-analyses of EDs and the risk of
cardiovascular events and mortality. We also review active ingredients,
pharmacokinetics, and the mechanism of action of EDs.
PMID- 28690956
TI - Thyrotoxicosis Mimicking ST Elevation Myocardial Infarction.
AB - Hyperthyroidism is well known to be associated with cardiac disease. Delay in
making the diagnosis and occurrence of complications are common and are
associated with a worse outcome. A 54-year-old male, non-smoker, with no past
medical history and no significant family history presented to our hospital with
severe left sided chest pain, "crushing" in nature. Electrocardiogram showed ST
segment elevations in the inferior leads. Troponin I level was 0.32 ng/mL (normal
range 0-0.05 ng/mL) on presentation. The patient underwent an emergent coronary
angiography which showed no evidence of occlusive coronary artery disease. The
patient's symptoms and signs prompted a high suspicion of thyrotoxicosis which
was subsequently confirmed by a low thyroid stimulating hormone and high free
thyroxine levels. The patient was given Methimazole and atenolol and his symptoms
resolved. Awareness of coronary vasospasm due to thyrotoxicosis should be raised
in patients presenting with typical angina pectoris with subsequent normal
coronary angiographic results. History and physical examination may suggest
underlying hyperthyroidism, but the absence of typical findings does not rule out
the diagnosis.
PMID- 28690957
TI - Point-of-Care Ultrasound for Jugular Venous Pressure Assessment: Live and Online
Learning Compared.
AB - INTRODUCTION: Point-of-care ultrasound (POCUS) is a novel technique for the
assessment of jugular venous pressure. Distance education may allow for efficient
dissemination of this technique. We compared online learning to a live course for
teaching ultrasonography jugular venous pressure (u-JVP) to determine if these
teaching methods yielded different levels of comfort with and use of u-JVP.
METHODS: This was an interventional trial of Canadian emergency physicians who
had taken a basic POCUS course. The participants were in one of three Groups:
online learning (Group OL), live teaching (Group LT), control (Group C). Group LT
participants also took an advanced course prior to the study that included
instruction in u-JVP. The participants who took the basic course were randomized
to Group OL or Group C. Group OL was subject to the intervention, online
learning. Group C only received an article citation regarding u-JVP.
Questionnaires were completed before and after the intervention. The primary
outcome was physician self-reported use and comfort with the technique of u-JVP
after online learning compared to live teaching. RESULTS: Of the 287 advanced
course participants, 42 completed the questionnaires (Group LT). Of the 3303
basic course participants, 47 who were assigned to Group OL completed the
questionnaires and 47 from Group C completed the questionnaires. Use of u-JVP
increased significantly in Group OL (from 15% to 55%) and Group C (from 21% to
47%) with the intervention. The comfort with use did not differ between Group LT
and Group OL (p=0.14). The frequency of use remained higher in Group LT than
Group OL (p=0.07). CONCLUSION: Online learning increases the use and comfort with
performing u-JVP for emergency physicians with prior POCUS experience. Although
the comfort with use of u-JVP was similar in Groups LT and OL, online learning
appears to yield levels of use that are less than those of a live course.
PMID- 28690958
TI - Application of Fluorescence In Situ Hybridization (FISH) Technique for the
Detection of Genetic Aberration in Medical Science.
AB - Fluorescence in situ hybridization (FISH) is a macromolecule recognition
technique, which is considered as a new advent in the field of cytology.
Initially, it was developed as a physical mapping tool to delineate genes within
chromosomes. The accuracy and versatility of FISH were subsequently capitalized
upon in biological and medical research. This visually appealing technique
provides an intermediate degree of resolution between DNA analysis and
chromosomal investigations. FISH consists of a hybridizing DNA probe, which can
be labeled directly or indirectly. In the case of direct labeling, fluorescent
nucleotides are used, while indirect labeling is incorporated with reporter
molecules that are subsequently detected by fluorescent antibodies or other
affinity molecules. FISH is applied to detect genetic abnormalities that include
different characteristic gene fusions or the presence of an abnormal number of
chromosomes in a cell or loss of a chromosomal region or a whole chromosome. It
is also applied in different research applications, such as gene mapping or the
identification of novel oncogenes. This article reviews the concept of FISH, its
application, and its advantages in medical science.
PMID- 28690959
TI - From the Gut to the Heart: Campylobacter jejuni Enteritis Leading to
Myopericarditis.
AB - Campylobacter jejuni enteritis is the most common enteric infection in the
developed world. Although rare, pericarditis and myopericarditis have been
increasingly documented as complications following campylobacteriosis. The
present paper implicates that myopericarditis and non-ischemic cardiomyopathy
following Campylobacter jejuni infection might be more prevalent than initially
thought and perhaps underreported so far. Therefore, it is imperative to perform
the appropriate initial diagnostic testing, including stool cultures, in order to
make an accurate diagnosis early in the course of the disease. Identifying the
etiology of myopericarditis as bacterial will ensure appropriate treatment with
antibiotics in addition to the cardiac medications needed for supportive care.
PMID- 28690960
TI - Complete Atlantooccipital Assimilation with Basilar Invagination and Atlantoaxial
Subluxation Treated Non-Surgically: A Case Report.
AB - Atlantooccipital assimilation is a partial or complete congenital fusion between
the atlas and the base of the occiput. Most patients with atlas assimilation are
asymptomatic, but some may present with neurological problems such as myelopathy.
We present the case of a 37-year-old woman who presented with neck and occipital
pain, episodic neck stiffness, and dizziness. Medical imaging revealed complete
atlantooccipital assimilation associated with basilar invagination, atlantoaxial
subluxation, and predisposing anterior spinal cord compression. The patient was
treated non-operatively with medications, cervical interferential therapy, and a
rigid cervical orthosis.
PMID- 28690961
TI - A Unique Presentation of an Intracranial Abscess Secondary to Retained Projectile
after Debridement with Dural Closure.
AB - Patients with penetrating head trauma with retained projectiles develop
intracranial abscesses as a common complication. The most common presentation is
a suddenly worsening headache. The most common pathogen identified is
staphylococcus. Outcomes are related to adherence of Matson's tenets. This case
study details the presentation of a 19-year-old patient that presented to the
neurological surgery clinic without neurologic deficits. Further questioning
revealed complaints of intermittent diffuse headaches with bilateral upper
extremity shock-like sensation for two weeks. Eight weeks prior he had undergone
right craniotomy, after a gunshot wound, for debridement and watertight dural
closure. The patient denied symptoms of fever, chills, nausea, vomiting,
diarrhea, or seizure. The patient presented with a noncontrast head computed
tomography (CT) which revealed retained projectile fragments without clear
evidence of abscess. On physical exam, the patient was without any neurological
deficit. Laboratory investigation revealed normal white blood cell count,
erythrocyte sedimentation rate, C-reactive protein, and negative blood cultures.
Head CT with contrast revealed a large intracerebral abscess adjacent to the
thalamus. The patient was taken to the operating room for repeat craniotomy with
resection of the abscess and removal of the intracranial projectile fragments.
Post-operatively, the patient remained neurology intact. Intraoperative cultures
were not significant for the growth of any bacteria. In eight weeks time, the
patient returned to his employment and his baseline level of activity. This case
underscores the importance of thorough assessment in patients with retained
intracranial projectiles as well as the need to routine follow-up. The unique
presentation of this patient prompted further investigation which elucidated a
lesion which correlated to his symptoms although laboratory assessment was
without abnormality.
PMID- 28690962
TI - Supracerebellar Infratentorial Endoscopic and Endoscopic-Assisted Approaches to
Pineal Lesions: Technical Report and Review of the Literature.
AB - The pineal gland has a deep central location, making it a surgeon's no man's
land. Surgical pathology within this territory presents a unique challenge and an
opportunity for employment of various surgical techniques. In modern times, the
microsurgical technique has been competing with the endoscope for achieving
superior surgical results. We describe two cases utilizing a purely endoscopic
and an endoscopic-assisted supracerebellar infratentorial approach in accessing
lesions of the pineal gland. We also discuss our early learning experience with
these approaches.
PMID- 28690963
TI - Charge transport in organic nanocrystal diodes based on rolled-up robust
nanomembrane contacts.
AB - The investigation of charge transport in organic nanocrystals is essential to
understand nanoscale physical properties of organic systems and the development
of novel organic nanodevices. In this work, we fabricate organic nanocrystal
diodes contacted by rolled-up robust nanomembranes. The organic nanocrystals
consist of vanadyl phthalocyanine and copper hexadecafluorophthalocyanine
heterojunctions. The temperature dependent charge transport through organic
nanocrystals was investigated to reveal the transport properties of ohmic and
space-charge-limited current under different conditions, for instance,
temperature and bias.
PMID- 28690964
TI - Bright fluorescent silica-nanoparticle probes for high-resolution STED and
confocal microscopy.
AB - In recent years, fluorescent nanomaterials have gained high relevance in
biological applications as probes for various fluorescence-based spectroscopy and
imaging techniques. Among these materials, dye-doped silica nanoparticles have
demonstrated a high potential to overcome the limitations presented by
conventional organic dyes such as high photobleaching, low stability and limited
fluorescence intensity. In the present work we describe an effective approach for
the preparation of fluorescent silica nanoparticles in the size range between 15
and 80 nm based on L-arginine-controlled hydrolysis of tetraethoxysilane in a
biphasic cyclohexane-water system. Commercially available far-red fluorescent
dyes (Atto647N, Abberior STAR 635, Dy-647, Dy-648 and Dy-649) were embedded
covalently into the particle matrix, which was achieved by aminosilane coupling.
The physical particle attributes (particle size, dispersion, degree of
agglomeration and stability) and the fluorescence properties of the obtained
particles were compared to particles from commonly known synthesis methods. As a
result, the spectroscopic characteristics of the presented monodisperse dye-doped
silica nanoparticles were similar to those of the free uncoupled dyes, but
indicate a much higher photostability and brightness. As revealed by dynamic
light scattering and zeta-potential measurements, all particle suspensions were
stable in water and cell culture medium. In addition, uptake studies on A549
cells were performed, using confocal and stimulated emission depletion (STED)
microscopy. Our approach allows for a step-by-step formation of dye-doped silica
nanoparticles in the form of dye-incorporated spheres, which can be used as
versatile fluorescent probes in confocal and STED imaging.
PMID- 28690965
TI - Fabrication of hierarchically porous TiO2 nanofibers by microemulsion
electrospinning and their application as anode material for lithium-ion
batteries.
AB - Titanium dioxide (TiO2) nanofibers have been widely applied in various fields
including photocatalysis, energy storage and solar cells due to the advantages of
low cost, high abundance and nontoxicity. However, the low conductivity of ions
and bulk electrons hinder its rapid development in lithium-ion batteries (LIB).
In order to improve the electrochemical performances of TiO2 nanomaterials as
anode for LIB, hierarchically porous TiO2 nanofibers with different tetrabutyl
titanate (TBT)/paraffin oil ratios were prepared as anode for LIB via a versatile
single-nozzle microemulsion electrospinning (ME-ES) method followed by calcining.
The experimental results indicated that TiO2 nanofibers with the higher
TBT/paraffin oil ratio demonstrated more axially aligned channels and a larger
specific surface area. Furthermore, they presented superior lithium-ion storage
properties in terms of specific capacity, rate capability and cycling performance
compared with solid TiO2 nanofibers for LIB. The initial discharge and charge
capacity of porous TiO2 nanofibers with a TBT/paraffin oil ratio of 2.25 reached
up to 634.72 and 390.42 mAh.g-1, thus resulting in a coulombic efficiency of
61.51%; and the discharge capacity maintained 264.56 mAh.g-1 after 100 cycles,
which was much higher than that of solid TiO2 nanofibers. TiO2 nanofibers with
TBT/paraffin oil ratio of 2.25 still obtained a high reversible capacity of
204.53 mAh.g-1 when current density returned back to 40 mA.g-1 after 60 cycles at
increasing stepwise current density from 40 mA.g-1 to 800 mA.g-1. Herein,
hierarchically porous TiO2 nanofibers have the potential to be applied as anode
for lithium-ion batteries in practical applications.
PMID- 28690966
TI - Carbon nanomaterials sensitize prostate cancer cells to docetaxel and mitomycin C
via induction of apoptosis and inhibition of proliferation.
AB - We have previously shown that carbon nanofibers (CNFs) and carbon nanotubes
(CNTs) can sensitize prostate cancer (PCa) cells to platinum-based
chemotherapeutics. In order to further verify this concept and to avoid a bias,
the present study investigates the chemosensitizing potential of CNFs and CNTs to
the conventional chemotherapeutics docetaxel (DTX) and mitomycin C (MMC), which
have different molecular structures and mechanisms of action than platinum-based
chemotherapeutics. DU-145 PCa cells were treated with DTX and MMC alone or in
combination with the carbon nanomaterials. The impact of the monotreatments and
the combinatory treatments on cellular function was then systematically analyzed
by using different experimental approaches (viability, short-term and long-term
proliferation, cell death rate). DTX and MMC alone reduced the viability of PCa
cells to 94% and 68%, respectively, whereas a combined treatment with CNFs led to
less than 30% remaining viable cells. Up to 17- and 7-fold higher DTX and MMC
concentrations were needed in order to evoke a similar inhibition of viability as
mediated by the combinatory treatments. In contrast, the dose of platinum-based
chemotherapeutics could only be reduced by up to 3-fold by combination with
carbon nanomaterials. Furthermore, combinatory treatments with CNFs led mostly to
an additive inhibition of short- and long-term proliferation compared to the
individual treatments. Also, higher cell death rates were observed in combinatory
treatments than in monotreatments, e.g., a combination of MMC and CNFs more than
doubled the cell death rate mediated by apoptosis. Combinations with CNTs showed
a similar, but less pronounced impact on cellular functions. In summary, carbon
nanomaterials in combination with DTX and MMC evoked additive to partly
synergistic anti-tumor effects. CNFs and CNTs possess the ability to sensitize
cancer cells to a wide range of structurally diverse chemotherapeutics and thus
represent an interesting option for the development of multimodal cancer
therapies. Co-administration of chemotherapeutics with carbon nanomaterials could
result in a reduction of the chemotherapeutic dosage and thus limit systemic side
effects.
PMID- 28690967
TI - Synthesis of [Fe(Leq)(Lax)] n coordination polymer nanoparticles using
blockcopolymer micelles.
AB - Spin-crossover compounds are a class of materials that can change their spin
state from high spin (HS) to low spin (LS) by external stimuli such as light,
pressure or temperature. Applications demand compounds with defined properties
concerning the size and switchability that are maintained when the compound is
integrated into composite materials. Here, we report the synthesis of
[Fe(Leq)(Lax)]n coordination polymer (CP) nanoparticles using self-assembled
polystyrene-block-poly(4-vinylpyridine) (PS-b-P4VP) block copolymer (BCP)
micelles as template. Variation of the solvent (THF and toluene) and the rigidity
of the axial ligand Lax (Lax = 1,2-di(pyridin-4-yl)ethane) (bpea), trans-1,2
di(pyridin-4-yl)ethene (bpee), and 1,2-di(pyridin-4-yl)ethyne) (bpey); Leq = 1,2
phenylenebis(iminomethylidyne)-bis(2,4-pentanedionato)(2-)) allowed the
determination of the preconditions for the selective formation of nanoparticles.
A low solubility of the CP in the used solvent and a high stability of the Fe-L
bond with regard to ligand exchange are necessary for the formation of composite
nanoparticles where the BCP micelle is filled with the CP, as in the case of the
[FeLeq(bpey)] n @BCP. Otherwise, in the case of more flexible ligands or ligands
that lead to high spin complexes, the formation of microcrystals next to the CP
BCP nanoparticles is observed above a certain concentration of [Fe(Leq)(Lax)] n .
The core of the nanoparticles is about 45 nm in diameter due to the templating
effect of the BCP micelle, independent of the used iron complex and
[Fe(Leq)(Lax)] n concentration. The spin-crossover properties of the composite
material are similar to those of the bulk for FeLeq(bpea)] n @BCP while
pronounced differences are observed in the case of [FeLeq(bpey)] n @BCP
nanoparticles.
PMID- 28690968
TI - Miniemulsion copolymerization of (meth)acrylates in the presence of
functionalized multiwalled carbon nanotubes for reinforced coating applications.
AB - Film forming, stable hybrid latexes made of methyl metacrylate (MMA), butyl
acrylate (BA) and 2-hydroxyethyl methacrylate (HEMA) copolymer reinforced with
modified multiwalled carbon nanotubes (MWCNTs) were synthesized by in situ
miniemulsion polymerization. The MWCNTs were pretreated by an air sonication
process and stabilized by polyvinylpyrrolidone. The presence of the MWCNTs had no
significant effect on the polymerization kinetics, but strongly affected the
polymer characteristics (Tg and insoluble polymer fraction). The performance of
the in situ composites was compared with that of the neat polymer dispersion as
well as with those of the polymer/MWCNT physical blends. The in situ composites
showed the presence of an additional phase likely due to the strong interaction
between the polymer and MWNCTs (including grafting) that reduced the mobility of
the polymer chains. As a result, a substantial increase of both the storage and
the loss moduli was achieved. At 60 degrees C, which is above the main
transition region of the polymer, the in situ composites maintained the
reinforcement, whereas the blends behaved as a liquid-like material. This
suggests the formation of a 3D network, in good agreement with the high content
of insoluble polymer in the in situ composites.
PMID- 28690969
TI - Two-dimensional silicon and carbon monochalcogenides with the structure of
phosphorene.
AB - Phosphorene has recently attracted significant interest for applications in
electronics and optoelectronics. Inspired by this material an ab initio study was
carried out on new two-dimensional binary materials with a structure analogous to
phosphorene. Specifically, carbon and silicon monochalcogenides have been
considered. After structural optimization, a series of binary compounds were
found to be dynamically stable in a phosphorene-like geometry: CS, CSe, CTe, SiO,
SiS, SiSe, and SiTe. The electronic properties of these monolayers were
determined using density functional theory. By using accurate hybrid functionals
it was found that these materials are semiconductors and span a broad range of
bandgap values and types. Similarly to phosphorene, the computed effective masses
point to a strong in-plane anisotropy of carrier mobilities. The variety of
electronic properties carried by these compounds have the potential to broaden
the technological applicability of two-dimensional materials.
PMID- 28690970
TI - 3D continuum phonon model for group-IV 2D materials.
AB - A general three-dimensional continuum model of phonons in two-dimensional
materials is developed. Our first-principles derivation includes full
consideration of the lattice anisotropy and flexural modes perpendicular to the
layers and can thus be applied to any two-dimensional material. In this paper, we
use the model to not only compare the phonon spectra among the group-IV materials
but also to study whether these phonons differ from those of a compound material
such as molybdenum disulfide. The origin of quadratic modes is clarified. Mode
coupling for both graphene and silicene is obtained, contrary to previous works.
Our model allows us to predict the existence of confined optical phonon modes for
the group-IV materials but not for molybdenum disulfide. A comparison of the long
wavelength modes to density-functional results is included.
PMID- 28690971
TI - Materials Knowledge Systems in Python - A Data Science Framework for Accelerated
Development of Hierarchical Materials.
AB - There is a critical need for customized analytics that take into account the
stochastic nature of the internal structure of materials at multiple length
scales in order to extract relevant and transferable knowledge. Data driven
Process-Structure-Property (PSP) linkages provide systemic, modular and
hierarchical framework for community driven curation of materials knowledge, and
its transference to design and manufacturing experts. The Materials Knowledge
Systems in Python project (PyMKS) is the first open source materials data science
framework that can be used to create high value PSP linkages for hierarchical
materials that can be leveraged by experts in materials science and engineering,
manufacturing, machine learning and data science communities. This paper
describes the main functions available from this repository, along with
illustrations of how these can be accessed, utilized, and potentially further
refined by the broader community of researchers.
PMID- 28690972
TI - Computational Psychiatry in Borderline Personality Disorder.
AB - PURPOSE OF REVIEW: We review the literature on the use and potential use of
computational psychiatry methods in Borderline Personality Disorder. RECENT
FINDINGS: Computational approaches have been used in psychiatry to increase our
understanding of the molecular, circuit, and behavioral basis of mental illness.
This is of particular interest in BPD, where the collection of ecologically valid
data, especially in interpersonal settings, is becoming more common and more
often subject to quantification. Methods that test learning and memory in social
contexts, collect data from real-world settings, and relate behavior to molecular
and circuit networks are yielding data of particular interest. SUMMARY: Research
in BPD should focus on collaborative efforts to design and interpret experiments
with direct relevance to core BPD symptoms and potential for translation to the
clinic.
PMID- 28690973
TI - Dynamic X-ray diffraction imaging of the ferroelectric response in bismuth
ferrite.
AB - X-ray diffraction imaging is rapidly emerging as a powerful technique by which
one can capture the local structure of crystalline materials at the nano- and
meso-scale. Here, we present investigations of the dynamic structure of epitaxial
monodomain BiFeO3 thin-films using a novel full-field Bragg diffraction imaging
modality. By taking advantage of the depth penetration of hard X-rays and their
exquisite sensitivity to the atomic structure, we imaged in situ and in operando,
the electric field-driven structural responses of buried BiFeO3 epitaxial thin
films in micro-capacitor devices, with sub-100 nm lateral resolution. These
imaging investigations were carried out at acquisition frame rates that reached
up to 20 Hz and data transfer rates of 40 MB/s, while accessing diffraction
contrast that is sensitive to the entire three-dimensional unit cell
configuration. We mined these large datasets for material responses by employing
matrix decomposition techniques, such as independent component analysis. We found
that this statistical approach allows the extraction of the salient physical
properties of the ferroelectric response of the material, such as coercive fields
and transient spatiotemporal modulations in their piezoelectric response, and
also facilitates their decoupling from extrinsic sources that are instrument
specific.
PMID- 28690974
TI - Laparoscopy in Blunt Abdominal Trauma: for Whom? When?and Why?
AB - The management of blunt abdominal trauma has evolved over time. While laparotomy
is the standard of care in hemodynamically unstable patients, stable patients are
usually treated by non-operative management (NOM), incorporating adjuncts such as
interventional radiology. However, although NOM has shown good results in solid
organ injuries, other lesions, namely those involving the hollow viscus,
diaphragm, and mesentery, do not qualify for this approach and need surgical
exploration. Laparoscopy can substantially reduce additional surgical aggression.
It has both diagnostic and therapeutic potential and, when negative, may reduce
the number of unnecessary laparotomies. Although some studies have shown
promising results on the use of laparoscopy in blunt abdominal trauma, randomized
controlled studies are lacking. Laparoscopy requires adequate training and
experience as well as sufficient staffing and equipment.
PMID- 28690975
TI - Reversible Plastic Deformation of Polymer Blends as a Means to Achieve
Stretchable Organic Transistors.
AB - Intrinsically stretchable semiconductors will facilitate the realization of
seamlessly integrated stretchable electronics. However, to date demonstrations of
intrinsically stretchable semiconductors have been limited. In this study, a new
approach to achieve intrinsically stretchable semiconductors is introduced by
blending a rigid high-performance donor-acceptor polymer semiconductor
poly[4(4,4dihexadecyl4Hcyclopenta [1,2b:5,4b' ] dithiopen2yl) alt [1,2,5]
thiadiazolo [3,4c] pyridine] (PCDTPT) with a ductile polymer semiconductor
poly(3hexylthiophene) (P3HT). Under large tensile strains of up to 75%, the
polymers are shown to orient in the direction of strain, and when the strain is
reduced, the polymers reversibly deform. During cyclic strain, the local packing
order of the polymers is shown to be remarkably stable. The saturated field
effect charge mobility is shown to be consistently above 0.04 cm2 V-1s-1 for up
to 100 strain cycles with strain ranging from 10% to 75% when the film is printed
onto a rigid test bed. At the 75% strain state, the charge mobility is
consistently above 0.15 cm2 V-1s-1. Ultimately, the polymer blend process
introduced here results in an excellent combination of device performance and
stretchability providing an effective approach to achieve intrinsically
stretchable semiconductors.
PMID- 28690976
TI - Interoperability: linking design and tolerancing with metrology.
AB - On October 30, 2014 the American National Standards Institute (ANSI) approved QIF
v 2.0 (Quality Information Framework, version 2.0) as an American National
Standard. Subsequently in early 2016 QIF version 2.1 was approved. This paper
describes how the QIF standard models the information necessary for quality
workflow across the full metrology enterprise. After a brief description of the
XML 'language' used in the standard, the paper reports on how the standard
enables information exchange among four major activities in the metrology
enterprise (product definition; measurement planning; measurement execution; and
the analysis and reporting of the quality data).
PMID- 28690978
TI - Exploring gold nanoparticle interactions with proteins and the tumor
microenvironment in biological systems.
PMID- 28690979
TI - Presentation, Treatment, and Prognosis of Secondary Melanoma within the Orbit.
AB - BACKGROUND: Ocular melanoma is a rare but often deadly malignancy that arises in
the uvea, conjunctiva, or orbit. Uveal melanoma is the most common type, with
conjunctival melanoma being the second most frequently observed. Melanoma
accounts for 5-10% of metastatic or secondary orbital malignancies, but only a
minute proportion of primary orbital neoplasia. The aim of this study was to
characterize the clinical presentation, treatment, and prognosis in patients
presenting with melanoma metastatic to, or secondary within, the orbit. METHODS:
A retrospective cohort study of patients presenting to a tertiary referral
orbital unit from 1982 to 2016 was performed. Eighty-nine patients with biopsy
proven diagnosis of melanoma within the orbit were included in the study. The
clinical notes, radiological imaging, histology, surgical notes, and outcome data
for the patients were reviewed. The main outcome measures of interest were the
interval between primary malignant melanoma and orbital presentation, survival
after orbital presentation, and clinical parameters (such as gender, age at
presentation, and treatment approach). RESULTS: The commonest primary source of
tumor was choroidal melanoma, with conjunctival and cutaneous melanomas being
relatively common; eyelid and naso-sinus tumors occurred in a few cases. The mean
age at presentation with orbital disease was 65 years (31-97 years). The interval
between primary malignancy and orbital disease (either local spread/recurrence or
true metastatic disease) showed wide variability, with almost one-third of
patients having orbital disease at the time of primary diagnosis, but others
presenting many years later; indeed, the longest orbital disease-free interval
was over 34 years. Twenty-three patients were considered to have had late orbital
metastases-that is, at more than 36 months after primary tumor. The median
survival following presentation with orbital involvement was 24 months. Patients
with tumors of cutaneous origin had worst survival, whereas those with
conjunctival tumors had the best prognosis. CONCLUSION: A high index of suspicion
for orbital recurrence should be maintained in any patient with prior history of
melanoma, however distant the primary tumor is in site or time. Furthermore,
giving a prognosis for orbital melanoma remains problematic due to highly
variable survival, and further investigation will be necessary to understand the
likely genetic basis of this phenomenon.
PMID- 28690977
TI - Regulation of the Mdm2-p53 signaling axis in the DNA damage response and
tumorigenesis.
AB - The p53 tumor suppressor acts as a guardian of the genome in mammalian cells
undergoing DNA double strand breaks induced by a various forms of cell stress,
including inappropriate growth signals or ionizing radiation. Following damage,
p53 protein levels become greatly elevated in cells and p53 functions primarily
as a transcription factor to regulate the expression a wide variety of genes that
coordinate this DNA damage response. In cells undergoing high amounts of DNA
damage, p53 can promote apoptosis, whereas in cells undergoing less damage, p53
promotes senescence or transient cell growth arrest and the expression of genes
involved in DNA repair, depending upon the cell type and level of damage. Failure
of the damaged cell to undergo growth arrest or apoptosis, or to respond to the
DNA damage by other p53-coordinated mechanisms, can lead to inappropriate cell
growth and tumorigenesis. In cells that have successfully responded to genetic
damage, the amount of p53 present in the cell must return to basal levels in
order for the cell to resume normal growth and function. Although regulation of
p53 levels and function is coordinated by many proteins, it is now widely
accepted that the master regulator of p53 is Mdm2. In this review, we discuss the
role(s) of p53 in the DNA damage response and in tumor suppression, and how post
translational modification of Mdm2 regulates the Mdm2-p53 signaling axis to
govern p53 activities in the cell.
PMID- 28690980
TI - CRH Affects the Phenotypic Expression of Sepsis-Associated Virulence Factors by
Streptococcus pneumoniae Serotype 1 In vitro.
AB - Sepsis is a life-threatening health condition caused by infectious pathogens of
the respiratory tract, and accounts for 28-50% of annual deaths in the US alone.
Current treatment regimen advocates the use of corticosteroids as adjunct
treatment with antibiotics, for their broad inhibitory effect on the activity and
production of pro-inflammatory mediators. However, despite their use,
corticosteroids have not proven to be able to reverse the death incidence among
septic patients. We have previously demonstrated the potential for neuroendocrine
factors to directly influence Streptococcus pneumoniae virulence, which may in
turn mediate disease outcome leading to sepsis and septic shock. The current
study investigated the role of Corticotropin-releasing hormone (CRH) in mediating
key markers of pneumococcal virulence as important phenotypic determinants of
sepsis and septic shock risks. In vitro cultures of serotype 1 pneumococcal
strain with CRH promoted growth rate, increased capsule thickness and penicillin
resistance, as well as induced pneumolysin gene expression. These results thus
provide significant insights of CRH-pathogen interactions useful in understanding
the underlying mechanisms of neuroendocrine factor's role in the onset of
community acquired pneumonias (CAP), sepsis and septic shock.
PMID- 28690981
TI - FNR Regulates the Expression of Important Virulence Factors Contributing to the
Pathogenicity of Avian Pathogenic Escherichia coli.
AB - Avian pathogenic Escherichia coli (APEC) is the etiologic agent of
colibacillosis, an important cause of morbidity and mortality in poultry. Though,
many virulence factors associated with APEC pathogenicity are known, their
regulation remains unclear. FNR (fumarate and nitrate reduction) is a well-known
global regulator that works as an oxygen sensor and has previously been described
as a virulence regulator in bacterial pathogens. The goal of this study was to
examine the role of FNR in the regulation of APEC virulence factors, such as Type
I fimbriae, and processes such as adherence and invasion, type VI secretion,
survival during oxidative stress, and growth in iron-restricted environments. To
accomplish this goal, APEC O1, a well-characterized, highly virulent, and fully
sequenced strain of APEC harboring multiple virulence mechanisms, some of which
are plasmid-linked, was compared to its FNR mutant for expression of various
virulence traits. Deletion of FNR was found to affect APEC O1's adherence,
invasion and expression of ompT, a plasmid-encoded outer membrane protein, type I
fimbriae, and aatA, encoding an autotransporter. Indeed, the fnr- mutant showed
an 8-fold reduction in expression of type I fimbriae and a highly significant (P
< 0.0001) reduction in expression of fimA, ompT (plasmid-borne), and aatA. FNR
was also found to regulate expression of the type VI secretion system, affecting
the expression of vgrG. Further, FNR was found to be important to APEC O1's
growth in iron-deficient media and survival during oxidative stress with the
mutant showing a 4-fold decrease in tolerance to oxidative stress, as compared to
the wild type. Thus, our results suggest that FNR functions as an important
regulator of APEC virulence.
PMID- 28690982
TI - Deferiprone and Gallium-Protoporphyrin Have the Capacity to Potentiate the
Activity of Antibiotics in Staphylococcus aureus Small Colony Variants.
AB - Small colony variants (SCVs) of bacteria like Staphylococcus aureus are
characterized by a reduced colony size and are linked to increased antibiotic
tolerance and resistance. Their altered expression of virulence factors, slow
growing properties and their ability to form biofilms make the eradication of
SCVs challenging. In the context of biofilm-related infectious diseases involving
S. aureus SCVs, a therapy targeting bacterial iron metabolism was evaluated. The
combination of the iron-chelator deferiprone (Def) and the heme-analog gallium
protoporphyrin (GaPP), in solution and incorporated in a surgical wound gel, was
tested for activity against planktonic and sessile SCVs. To this end, the
activity of Def-GaPP was assessed against planktonic S. aureus SCVs, as well as
against in vitro and in vivo biofilms in the colony biofilm model, an artificial
wound model and a Caenorhabditis elegans infection model. While Def alone failed
to show substantial antibacterial activity, GaPP and the combination of Def-GaPP
demonstrated concentration- and strain-dependent antibacterial properties.
Specifically, the Def-GaPP combination significantly reduced the bacterial load
in an artificial wound model and increased the survival of S. aureus SCV infected
C. elegans. When Def-GaPP were combined with gentamicin or ciprofloxacin, the
triple combinations exceeded the antibiofilm activity of the individual compounds
in the colony biofilm model. In targeting bacterial iron metabolism, Def-GaPP
showed significant activity against planktonic and sessile SCVs. Moreover, Def
GaPP could potentiate the activity of gentamicin and ciprofloxacin. Delivered in
a wound healing gel, Def-GaPP showed promise as a new topical strategy against
infections with S. aureus SCVs.
PMID- 28690984
TI - The rapid internationalization of Annals of Pediatric Endocrinology & Metabolism
as evidenced by journal metrics.
AB - PURPOSE: Using journal metrics, this paper explores whether Annals of Pediatric
Endocrinology & Metabolism has internationalized 4 years after changing its
language to English only. METHODS: From the journal's website and the Web of
Science Core Collection, the following metrics were counted or calculated: Number
of citable articles, countries of authors and editorial board members, total
citations, impact factor, countries of citing authors, citing journal titles, and
Hirsch index. RESULTS: From 2012 to 2017, 208 articles were citable. The authors
had affiliations in 7 countries and the editorial board members in 14 countries.
From 2014 to 2017, the total citations each year were 8, 81, 141, and 61; and the
impact factors from 2014 to 2016 were calculated as 0.05, 0.987, and 1.165. The
citing authors were from 60 countries, among which the United States, China,
South Korea, Italy, and Germany were most common. The journal was cited by 215
journal titles. The Hirsch index was 7. CONCLUSION: These journal metrics showed
that the journal achieved international status 4 years after changing the
journals' language into English only. The journal's language policy successfully
enabled the journal to rebrand as an international journal.
PMID- 28690985
TI - Metabolic syndrome induced by anticancer treatment in childhood cancer survivors.
AB - The number of childhood cancer survivors is increasing as survival rates improve.
However, complications after treatment have not received much attention,
particularly metabolic syndrome. Metabolic syndrome comprises central obesity,
dyslipidemia, hypertension, and insulin resistance, and cancer survivors have
higher risks of cardiovascular events compared with the general population. The
mechanism by which cancer treatment induces metabolic syndrome is unclear.
However, its pathophysiology can be categorized based on the cancer treatment
type administered. Brain surgery or radiotherapy may induce metabolic syndrome by
damaging the hypothalamic-pituitary axis, which may induce pituitary hormone
deficiencies. Local therapy administered to particular endocrine organs directly
damages the organs and causes hormone deficiencies, which induce obesity and
dyslipidemia leading to metabolic syndrome. Chemotherapeutic agents interfere
with cell generation and growth, damage the vascular endothelial cells, and
increase the cardiovascular risk. Moreover, chemotherapeutic agents induce
oxidative stress, which also induces metabolic syndrome. Physical inactivity
caused by cancer treatment or the cancer itself, dietary restrictions, and the
frequent use of antibiotics may also be risk factors for metabolic syndrome.
Since childhood cancer survivors with metabolic syndrome have higher risks of
cardiovascular events at an earlier age, early interventions should be
considered. The optimal timing of interventions and drug use has not been
established, but lifestyle modifications and exercise interventions that begin
during cancer treatment might be beneficial and tailored education and
interventions that account for individual patients' circumstances are needed.
This review evaluates the recent literature that describes metabolic syndrome in
cancer survivors, with a focus on its pathophysiology.
PMID- 28690986
TI - Next generation sequencing and array-based comparative genomic hybridization for
molecular diagnosis of pediatric endocrine disorders.
AB - Next-generation sequencing (NGS) and array-based comparative genomic
hybridization (array CGH) have enabled us to perform high-throughput mutation
screening and genome-wide copy number analysis, respectively. These methods can
be used for molecular diagnosis of pediatric endocrine disorders. NGS has
determined the frequency and phenotypic variation of mutations in several disease
associated genes. Furthermore, whole exome analysis using NGS has successfully
identified several novel causative genes for endocrine disorders. Array CGH is
currently used as the standard procedure for molecular cytogenetic analysis.
Array CGH can detect various submicroscopic genomic rearrangements involving
exons or enhancers of disease-associated genes. This review introduces some
examples of the use of NGS and array CGH for the molecular diagnosis of pediatric
endocrine disorders.
PMID- 28690987
TI - The influence of gonadotropin releasing hormone agonist treatment on the body
weight and body mass index in girls with idiopathic precocious puberty and early
puberty.
AB - PURPOSE: This study aimed to investigate the influence of gonadotropin releasing
hormone agonist (GnRHa) treatment on the weight and body mass index (BMI) of
girls who were diagnosed with idiopathic central precocious puberty (CPP) or
early puberty (EP). METHODS: Patients who were younger than 8 years of age at
diagnosis were classified as CPP and patients aged between 8 and 9 years at
diagnosis were classified as EP. Of 129 patients, 34 were diagnosed with CPP and
95 were diagnosed with EP. The patients were divided according to pretreatment
weight status into normal weight group, an overweight group, or an obese group.
RESULTS: No significant changes were observed with respect to the weight standard
deviation score (SDS) before and after 1 year, 2 years of treatment, respectively
(P>0.05, P>0.05) in all patient groups. No significant changes were observed in
relation to the BMI SDS before and after 1 year, 2 years of treatment,
respectively (P>0.05, P>0.05) in all patient group. Depending on the degree of
obesity, differences with respect to the weight SDS and BMI SDS were observed.
CONCLUSION: BMI SDS increased in the GnRHa-treated patients as a whole group, but
was not statistically significant. But BMI SDS increased significantly in the
normal weight group after 2 years of GnRHa treatment. So, GnRHa treatment may
affect the change of BMI SDS depending on degree of obesity.
PMID- 28690988
TI - Intellectual development in preschool children with early treated congenital
hypothyroidism.
AB - PURPOSE: Delayed treatment of congenital hypothyroidism (CH) is a common cause of
mental retardation. The aim of the present study was to evaluate intellectual
outcomes in preschool children with treated CH. METHODS: We retrospectively
reviewed the clinical records of 43 children (age range: 13 to 60 days of life;
22 girls and 21 boys) diagnosed with CH. Children aged 5 to 7 years were examined
using the Korean Wechsler Intelligence Scale for Children or the Korean Wechsler
Preschool and Primary Scale of Intelligence. RESULTS: The patients started
treatment between 13 and 60 days of age. The mean intelligence quotient (IQ) of
patients tested at age 5 to 7 years was 103.14+/-11.68 (IQ range: 76-126). None
had intellectual disability (defined as an IQ <70). Twenty-one subjects were
treated with a low dose (6.0-9.9 ug/kg/day) and 22 with a high dose of
levothyroxine (10.0-16.0 ug/kg/day). There was no significant difference in the
mean full-scale IQ (FSIQ), verbal IQ (VIQ), and performance IQ (PIQ) scores
between the 2 groups. FSIQ, PIQ, and VIQ scores were not significantly correlated
with initial dose of L-T4, initial fT4, age at treatment in multivariate
analysis. CONCLUSION: IQ scores of subjects with early treated CH diagnosed
through a neonatal screening test were within normal range, regardless of
etiology, thyroid function, initial dose of levothyroxine, and age at start of
treatment.
PMID- 28690983
TI - The Essential Role of Tick Salivary Glands and Saliva in Tick Feeding and
Pathogen Transmission.
AB - As long-term pool feeders, ticks have developed myriad strategies to remain
discreetly but solidly attached to their hosts for the duration of their blood
meal. The critical biological material that dampens host defenses and facilitates
the flow of blood-thus assuring adequate feeding-is tick saliva. Saliva exhibits
cytolytic, vasodilator, anticoagulant, anti-inflammatory, and immunosuppressive
activity. This essential fluid is secreted by the salivary glands, which also
mediate several other biological functions, including secretion of cement and
hygroscopic components, as well as the watery component of blood as regards hard
ticks. When salivary glands are invaded by tick-borne pathogens, pathogens may be
transmitted via saliva, which is injected alternately with blood uptake during
the tick bite. Both salivary glands and saliva thus play a key role in
transmission of pathogenic microorganisms to vertebrate hosts. During their long
co-evolution with ticks and vertebrate hosts, microorganisms have indeed
developed various strategies to exploit tick salivary molecules to ensure both
acquisition by ticks and transmission, local infection and systemic dissemination
within the vertebrate host.
PMID- 28690989
TI - The association between skeletal maturation and adrenal androgen levels in obese
children and adolescents.
AB - PURPOSE: This study aimed to investigate the association between skeletal
maturation and adrenal androgen levels in obese children and adolescents.
METHODS: Fifty-three children and adolescents (aged 7-15 years) diagnosed as
obese or overweight were investigated. Anthropometric measurements, bone age (BA)
determination, serum biochemical analyses, and hormonal measurements were
performed. The difference between BA and chronological age (BA-CA, dBACA) was
calculated and used to represent the degree of advanced skeletal maturation.
RESULTS: Thirty-one subjects were classified into the obese group and 22 subjects
into the overweight group. Insulin resistance as calculated by the homeostasis
model assessment of insulin resistance (HOMA-IR) was significantly higher in the
obese group than in the overweight group (4.03+/-2.20 vs. 2.86+/-1.11, P=0.026).
The skeletal maturation of the obese group was advanced, but the dBACA did not
differ between the obese and overweight groups statistically (1.43+/-1.35 vs.
0.91+/-1.15, P=0.141). Serum dehydroepiandrosterone sulfate (DHEA-S) levels were
significantly higher in subjects with dBACA>1 compared to those with dBACA<=1
(104.3+/-62.2 vs. 59.6+/-61.0, P=0.014). Correlation analyses demonstrated that
dBACA was positively correlated with body mass index standard deviation scores
(r=0.35, P=0.010), fasting insulin (r=0.36, P=0.009), HOMA-IR (r=0.30, P=0.031),
and insulin-like growth factor-binding protein-3 (r=0.331, P=0.028). In
multivariate linear regression analysis, HOMA-IR (P=0.026) and serum DHEA-S
(P=0.032) were positively correlated with the degree of advanced skeletal
maturation. CONCLUSION: Advanced skeletal maturation is associated with increased
insulin resistance and elevated DHEA-S levels in obese children and adolescents.
PMID- 28690990
TI - Predictors of transient congenital hypothyroidism in children with eutopic
thyroid gland.
AB - PURPOSE: Congenital hypothyroidism (CH) is the most common cause of preventable
mental retardation. Recently, the detection of CH cases with eutopic thyroid
gland has increased due to neonatal screening programs. In this study, we aimed
to identify and evaluate predictive factors that could distinguish between
permanent and transient CH in patients with eutopic thyroid gland. METHODS: We
retrospectively reviewed 100 children diagnosed with CH and with eutopic thyroid
gland. All subjects were treated with levothyroxine and underwent re-evaluation
after 3 years of age. RESULTS: Of the 100 CH patients, 35 (35.0%) were diagnosed
with permanent CH (PCH) and 65 (65.0%) were diagnosed with transient CH (TCH).
The initial thyroid stimulating hormone levels were significantly lower in the
TCH subjects than in PCH subjects. In addition, the mean doses of levothyroxine
(ug/kg/day) at the 1st, 2nd, and 3rd year of treatment were significantly lower
in subjects with TCH than in PCH subjects with eutopic thyroid gland. Based on
the receiver operating characteristic (ROC) curve, the optimal cutoff dose of
levothyroxine at 3 years of 2.76 ug/kg/day could predict TCH, and was associated
with 87.3% sensitivity and 67.6% specificity, with an area under the ROC curve of
0.769. CONCLUSION: The levothyroxine dose requirement during treatment period has
a predictive role in differentiating TCH from PCH in CH patients with eutopic
thyroid gland.
PMID- 28690991
TI - Effect of growth hormone treatment on children with idiopathic short stature and
idiopathic growth hormone deficiency.
AB - PURPOSE: There are inconsistencies in the results reported in a small number of
previous studies into growth hormone (GH) treatment in Korean children with
idiopathic short stature (ISS) and idiopathic growth hormone deficiency (IGHD).
Thus, the authors retrospectively compared the effects of GH in ISS and IGHD.
METHODS: From the medical records of 26 ISS and 30 IGHD children, auxological and
biochemical changes including chronologic age (CA), bone age (BA), height
standard deviation score (HT-SDS), predicted adult height (PAH), midparental
height (MPH), insulin-like growth factor-1 (IGF-1), and insulin-like growth
factor binding protein-3 (IGFBP-3) were compared. RESULTS: Before treatment, IGHD
group had younger BA, lower BA/CA ratio, and lower IGF-1 level than those in the
ISS group. During GH treatment, the levels of IGF-1 and IGFBP-3 were not
different. Although annual BA increment was higher in IGHD group, and annual PAH
SDS increment was higher in ISS group, annual HT-SDS increments were not
different. Both HT-SDS and PAH-SDS in the ISS group increased significantly until
the end of the second year, and then those were not significantly different from
MPH-SDS. In the IGHD group, the HT-SDS showed a significant increase till the end
of the second year, and the PAH-SDS was not significantly changed at each year,
but both HT-SDS and PAH-SDS were not significantly different from MPH-SDS at the
end of the third year. CONCLUSION: During GH treatment, both HT-SDS and PAH-SDS
approached the genetic target range of MPH-SDS after 2 years in ISS children and
3 years in IGHD children.
PMID- 28690992
TI - Diabetes mellitus due to agenesis of the dorsal pancreas in a patient with
heterotaxy syndrome.
AB - Heterotaxy syndrome (HS) is a congenital disorder resulting from an abnormal
arrangement of visceral organs across the normal left-right axis in the embryonic
period. HS is usually associated with multiple anomalies, including defects of
the major cardiovascular system and the extracardiovascular system such as
intestinal malrotation, abnormal lung lobulation, bronchus anomalies, and
pancreatic dysplasia. Although pancreatic dysplasia is occasionally accompanied
with HS, the occurrence of diabetes mellitus (DM) due to pancreatic dysplasia in
HS is rarely reported. We here report a case involving 13-year-old girl with DM
caused by agenesis of the dorsal pancreas and HS diagnosed on the basis of the
presence of a double-outlet right ventricle with bilateral pulmonary stenosis and
intestinal malrotation with duodenal cyst. Timely diagnosis and treatment with
insulin improved glycemic control.
PMID- 28690993
TI - 2q37 Deletion syndrome confirmed by high-resolution cytogenetic analysis.
AB - Chromosome 2q37 deletion syndrome is a rare chromosomal disorder characterized by
mild to moderate developmental delay, brachydactyly of the third to fifth digits
or toes, short stature, obesity, hypotonia, a characteristic facial appearance,
and autism spectrum disorder. Here, we report on a patient with 2q37 deletion
presenting with dilated cardiomyopathy (DCMP). Congenital heart malformations
have been noted in up to 20% of patients with 2q37 deletions. However, DCMP has
not been reported in 2q37 deletion patients previously. The patient exhibited the
characteristic facial appearance (a flat nasal bridge, deep-set eyes, arched
eyebrows, and a thin upper lip), developmental delay, mild mental retardation,
peripheral nerve palsy, and Albright hereditary osteodystrophy (AHO)-like
phenotypes (short stature and brachydactyly). Conventional chromosomal analysis
results were normal; however, microarray-based comparative genomic hybridization
revealed terminal deletion at 2q37.1q37.3. In addition, the patient was confirmed
to have partial growth hormone (GH) deficiency and had shown a significant
increase in growth rate after substitutive GH therapy. Chromosome 2q37 deletion
syndrome should be considered in the differential diagnosis of patients
presenting with AHO features, especially in the presence of facial dysmorphism.
When patients are suspected of having a 2q37 deletion, high-resolution
cytogenetic analysis is recommended.
PMID- 28690994
TI - Delayed diagnosis of 22q11 deletion syndrome due to late onset hypocalcemia in a
11-year-old girl with imperforated anus.
AB - Neonatal hypocalcemia and congenital heart defects has been known as the first
clinical manifestation of the chromosome 22q11.2 deletion syndrome (22q11DS).
However, because of its wide clinical spectrum, diagnosis of 22q11DS can be
delayed in children without classic symptoms. We report the case of a girl with
the history of imperforate anus but without neonatal hypocalcemia or major
cardiac anomaly, who was diagnosed for 22q11DS at the age of 11 after the onset
of overt hypocalcemia. She was born uneventfully from phenotypically normal
Korean parents. Imperforate anus and partial cleft palate were found at birth,
which were surgically repaired thereafter. There was no history of neonatal
hypocalcemia, and karyotyping by GTG banding was normal. At the age of 11,
hypocalcemia (serum calcium, 5.0 mg/dL) and decreased parathyroid hormone level
(10.8 pg/mL) was noted when she visited our Emergency Department for fever and
vomiting. The 22q11DS was suspected because of her mild mental retardation and
velopharyngeal insufficiency, and a microdeletion on chromosome 22q11.2 was
confirmed by fluorescence in situ hybridization. The 22q11DS should be considered
in the differential diagnosis of hypocalcemia at any age because of its wide
clinical spectrum.
PMID- 28690995
TI - Pediatric Vascular Surgery Review with a 30-Year-Experience in a Tertiary
Referral Center.
AB - Pediatric vascular disease is rare, and remains a big challenge to vascular
surgeons. In contrast to adults, surgery for pediatric vascular disease is
complicated by issues related to small size, future growth, and availability of
suitable vascular conduit. During the last 30 years, 131 major vascular
operations were performed in a tertiary referral center, Seoul National
University Hospital, including aortoiliac aneurysm, acute or chronic arterial
occlusion, renovascular hypertension, portal venous hypertension, trauma, tumor
invasion to major abdominal vessels, and others. Herein we review on the
important pediatric vascular diseases and share our clinical experiences on these
rare diseases.
PMID- 28690996
TI - Long Term Outcomes of Femorofemoral Crossover Bypass Grafts.
AB - PURPOSE: Femorofemoral crossover bypass (FCB) is a good procedure for patients
with unilateral iliac artery disease. There are many articles about the results
of FCB, but most of them were limited to 5 years follow-up. The purpose of our
study was to analysis the results of FCB with a 10-year follow-up period.
MATERIALS AND METHODS: Between January 1995 and December 2010, 133 patients were
operated in Samsung Medical Center (median follow-up: 58.8 months). We
retrospectively analysed patient characteristics, the preoperative treatment, the
operative procedure, and material used. RESULTS: The indications for FCB were
claudication in 110 and critical limb ischemia in 23 patients. Three patients
were died due to myocardiac infarction, intracranial hemorrhage, and acute
respiratory failure within 30 days after surgery. The one-year primary and
secondary patency rates were 89% and 97%, the 5-year primary and secondary
patency rates were 70% and 85%, and the 10-year primary and secondary patency
rates were 31% and 67%. The 5-year and 10-year limb salvage rates were 97% and
95%, respectively. CONCLUSION: Our long term analysis suggests that FCB might be
a valuable alternative treatment modality in patients with unilateral iliac
artery disease.
PMID- 28690997
TI - Endovascular Aneurysm Repair in Patients with Conical Neck Anatomy.
AB - PURPOSE: Cone shape neck is regarded as non-instruction for use (IFU) in most
commercial stent graft. However, in real practice, liberal application of
endovascular aneurysm repair (EVAR) for outside of IFU happens. We investigate
non-adherence to conical neck anatomy in terms of early aneurysmal exclusion
results. MATERIALS AND METHODS: From January 2010 to December 2013, 105 patients
with abdominal aortic aneurysm (AAA) underwent EVAR in Daegu Catholic University
Medical Center. Among them, 38 patients (36.2%) had AAA with conical neck. We
investigated the clinical characteristics of patients and the details of conical
neck. We also analyzed the clinical results, such as endoleak, migration,
procedure failure, perioperative mortality, and admission duration between
conical neck and non-conical neck. RESULTS: The maximum diameter of AAA was
larger (60.95 mm vs. 52.68 mm, P=0.016) and the infrarenal neck length was
shorter (25.07 mm vs. 38.13 mm, P=0.000) in conical neck group. During the
procedure, type Ia endoleak occurred more in conical neck group (23.7% vs. 6.0%,
P=0.013) and it could be successfully solved with additional adjunctive
treatments, such as balloon or Palmaz stent. Although there was no statistical
significance, mortality was higher and admission duration was longer in the
conical neck (15.8% vs. 6.0%, 16.62+/-13.12 days vs. 13.03+/-13.13 days). Mean
follow-up duration was 319.2+/-366.45 days. Successful aneurysmal exclusion was
achieved. CONCLUSION: The presence of conical neck may not be a contraindication
for EVAR. However, conical neck requires careful observation for additional
adjunctive treatments because it increases the risk of type Ia endoleak.
PMID- 28690998
TI - Results of Infrainguinal Bypass with a Composite Graft Combining
Polytetrafluoroethylene and Vein Graft in Absence of Appropriate Saphenous Vein
Graft.
AB - PURPOSE: Use of a composite graft combining a polytetrafluoroethylene graft with
an autogenous vein is an option for limb salvage in the absence of an adequate
single segment vein graft. We aimed to investigate the results of infrainguinal
bypass with a composite graft. MATERIALS AND METHODS: We retrospectively reviewed
11 infrainguinal arterial bypasses on 11 limbs which underwent surgery from March
2012 to November 2016. RESULTS: Critical limb ischemia was common (63.6%)
indication of bypass surgery and most (90.9%) of the patients had history of
failed previous treatment including endovascular treatment (36.4%) and bypass
surgery (72.7%). At the 2 years after graft implantations, primary patency and
amputation-free survival of below-knee bypasses using composite graft were 73%
and 76%, respectively. CONCLUSION: Infrainguinal arterial bypasses with composite
graft had an acceptable patency. In patients without other alternative conduits
for revascularization, bypass with a composite graft can be an option.
PMID- 28690999
TI - Early Experiences of Sandwich Technique to Preserve Pelvic Circulation during
Endovascular Aneurysm Repair.
AB - PURPOSE: To report experiences of the sandwich technique (ST) for preservation of
pelvic flow during endovascular repair of complex aortic or aortoiliac aneurysms.
MATERIALS AND METHODS: Eight patients underwent elective endovascular aneurysm
repair (EVAR) using the ST between March 2013 and February 2017. The anatomic
indications for the ST were complex aortoiliac aneurysms (5 cases), abdominal
aortic aneurysms (AAA) with non-diseased short common iliac arteries (2 cases)
and AAA with unilateral occluded iliac artery (1 case). The ST was performed
through both femoral and brachial approach. Patient clinical and radiologic data
were collected and analyzed. RESULTS: Eight patients (7 male; mean age, 73.4
years) were followed over a mean period of 277 days (range, 9-1,106 days). The
technical success rate was 100%. The primary patency rate of the iliac stent
grafts was 88% (14/16 cases). One internal iliac and 1 external iliac stent-graft
occlusion was observed during the early postoperative period. There was 1 gutter
endoleak which disappeared spontaneously within 4 days, and there were 2 type II
endoleaks: one treated by coil embolization after 13 months, and the other
observed without treatment. There were no cases of sac growth or aneurysm-related
deaths, and no cases of buttock claudication or impotence. CONCLUSION: The ST is
a safe and feasible technique to preserve pelvic circulation during endovascular
treatment of complex aortoiliac aneurysms. The need to expand the indications for
complex EVARs with adjunctive procedures, such as the ST is highlighted in
situations where branched/fenestrated device availability is limited.
PMID- 28691000
TI - Late Type 3b Endoleak Mimicking Type 2 Endoleak after Endovascular Aortic
Aneurysm Repair.
AB - Endovascular abdominal aortic aneurysm (AAA) repair has been widely used for the
treatment of AAA as a safe and efficient method, but endoleaks causing persistent
expansion of aneurysm sac may cause aneurysmal rupture and death. Type 3 endoleak
is rare but a predominant cause of late rupture. Type 3b endoleak can be
misdiagnosed as type 2 endoleak, which is more frequent. Here we report two cases
of type 3b endoleak mimicking type 2 endoleak, which were successfully treated by
open surgery of partial explantation of the stent-graft and endoaneurysmal
interposition graft replacement.
PMID- 28691001
TI - Hand-Assisted Laparoscopic Nephrectomy and Auto-Transplantation for a Hilar Renal
Artery Aneurysm: A Case Report.
AB - A 52-year-old man was admitted with an incidentally detected right renal artery
aneurysm (RAA). Computed tomographic angiography with three-dimensional
reconstruction revealed that the aneurysm was 2.2 cm in diameter and located at
the renal hilum. We performed hand-assisted laparoscopic nephrectomy with ex vivo
repair of the RAA and auto-transplantation with minimal elongation of Gibson
incision. The operation and postoperative course were uneventful. At last follow
up, the patient was alive with a well-functioning auto-transplant. Hand-assisted
laparoscopic nephrectomy and auto-transplantation is a useful treatment option
for hilar RAA.
PMID- 28691002
TI - How Do Masters of Public Health Programs Teach Monitoring and Evaluation?
AB - INTRODUCTION: The health systems in developing countries face challenges because
of deficient monitoring and evaluation (M&E) capacity with respect to their
knowledge, skills, and practices. Strengthening M&E training in public health
education can help overcome the gaps in M&E capacity. There is a need to advance
the teaching of M&E as a core element of public health education. OBJECTIVES: To
review M&E teaching across Masters of Public Health programs and to identify core
competencies for M&E teaching in South Asian context. MATERIALS AND METHODS: We
undertook two activities to understand the M&E teaching across masters level
programs: (1) desk review of M&E curriculum and teaching in masters programs
globally and (2) review of M&E teaching across 10 institutions representing 4
South Asian countries. Subsequently, we used the findings of these two activities
as inputs to identify core competencies for an M&E module through a consultative
meeting with the 10 South Asian universities. RESULTS: Masters programs are being
offered globally in 321 universities of which 88 offered a Masters in Public
Health, and M&E was taught in 95 universities. M&E was taught as a part of
another module in 49 institutions. The most common duration of M&E teaching was 4
5 weeks. From the 70 institutes where information on electives was available, M&E
was a core module/part of a core module at 42 universities and an elective at 28
universities. The consultative meeting identified 10 core competencies and draft
learning objectives for M&E teaching in masters programs in South Asia.
CONCLUSION: The desk review showed similarities in M&E course content but
variations in course structure and delivery. The core competencies identified
during the consultation included basic M&E concepts. The results of the review
and the core competencies identified at the consultation are useful resources for
institutions interested in refining/updating M&E curricula in their postgraduate
degree programs. Our approach for curriculum development as well as the consensus
building experience could also be adapted for use in other situations.
PMID- 28691003
TI - Leadership Development of Rehabilitation Professionals in a Low-Resource Country:
A Transformational Leadership, Project-Based Model.
AB - BACKGROUND AND RATIONALE: This paper presents an overview of the activities and
outcomes of the Leadership Institute (LI), a short-term leadership development
professional development course offered to physiotherapists in a low-resource
country. Previous studies have provided examples of the benefits of such programs
in medicine and nursing, but this has yet to be documented in the rehabilitation
literature. The prototype of leadership development presented may provide
guidance for similar trainings in other low-resource countries and offer the
rehabilitation community an opportunity to build on the model to construct a
research agenda around rehabilitation leadership development. PEDAGOGY: The
course used a constructivist approach to integrate participants' experiences,
background, beliefs, and prior knowledge into the content. Transformational
leadership development theory was emphasized with the generation of active
learning projects, a key component of the training. OUTCOMES: Positive changes
after the course included an increase in the number of community outreach
activities completed by participants and increased involvement with their
professional organization. Thirteen leadership projects were proposed and
presented. DISCUSSION: The LI provided present and future leaders throughout
Rwanda with exposure to transformative leadership concepts and offered them the
opportunity to work together on projects that enhanced their profession and met
the needs of underserved communities. CONSTRAINTS AND CHALLENGES: Challenges
included limited funding for physiotherapy positions allocated to hospitals in
Rwanda, particularly in the rural areas. Participants experienced difficulties in
carrying out leadership projects without additional funding to support them.
LESSONS LEARNED: While the emphasis on group projects to foster local advocacy
and community education is highly recommended, the projects would benefit from a
strong long-term mentorship program and further budgeting considerations.
CONCLUSION: The LI can serve as a model to develop leadership skills and spur
professional growth in low-resource settings. Leadership development is necessary
to address worldwide inequities in health care. The LI model presents a method to
cultivate transformational leadership and work toward improvements in health care
and delivery of service.
PMID- 28691004
TI - Population Knowledge, Attitude, and Practice Regarding Helicobacter pylori
Transmission and Outcomes: A Literature Review.
AB - BACKGROUND: Helicobacter pylori infection is associated with the development of
chronic gastritis, peptic ulcer disease, and gastric cancer. Current clinical
recommendations are that H. pylori test-and-treat should be individualized based
on comorbidities and patient preferences among populations at increased risk for
certain morbidities. However, knowledge, attitudes and practices regarding H.
pylori among potential patient populations are largely unknown. MATERIALS: We
conducted a literature review to assess knowledge, attitudes, and practices of
patients or community populations around H. pylori transmission, prevention, and
associated morbidity. RESULTS: Nine studies met the inclusion criteria, all
published between 1997 and 2014. Eight studies evaluated perception of H. pylori
among at-risk populations, while one study evaluated perception among a general
population. The studies suggest inconsistencies between the perceptions of these
populations and the established understanding of knowledge, attitude, and
preventive practices for H. pylori among even at-risk populations. CONCLUSION: To
adequately respond to current test-and-treat recommendations for treatment of H.
pylori, general population education must be implemented, especially among at
risk populations. Further work is needed within at-risk populations in the United
States to determine prevalence of H. pylori and their current knowledge if
adequate prevention strategies are to be designed.
PMID- 28691005
TI - Corrigendum: A CRISPR New World: Attitudes in the Public toward Innovations in
Human Genetic Modification.
AB - [This corrects the article on p. 117 in vol. 5, PMID: 28589120.].
PMID- 28691006
TI - Serum Vitamin A Levels May Affect the Severity of Ocular Graft-versus-Host
Disease.
AB - Allogeneic hematopoietic stem cell transplantation (HSCT) is a well-established
therapeutic option for a range of inherited and acquired hematological disorders.
However, graft-versus-host disease (GVHD) remains the leading cause of non
relapse mortality in allogeneic HSCT recipients. Ocular involvement occurs in up
to 80% of chronic GVHD patients. In our cases, the diagnosis of vitamin A
deficiency was suspected for GVHD patients. Serum vitamin A measurements were
conducted to confirm clinical suspicions. Our study revealed significant decrease
in serum levels of vitamin A in chronic liver GVHD patients. Although there have
been many studies evaluating ocular manifestations in patients with GVHD, the
present study is, to our knowledge, the first to study the relationship between
vitamin A and ocular manifestations of GVHD in humans. Our data suggest that
vitamin A deficiency affects the severity of ocular GVHD in adults.
PMID- 28691007
TI - A Comprehensive Analysis of the Current Status and Unmet Needs in Kidney
Transplantation in Southeast Asia.
AB - To address the unmet needs in the face of a growing demand for end-stage renal
failure management and kidney transplantation in Asia, we have conducted a
critical analysis of published literature and national registries to evaluate
clinical outcomes and the rates of organ donation in Southeast Asia and the
challenges facing these regions with regards to regulation, choice of donor
source, and funding. Based on the available data, suggestions are proposed for an
advancement of rates of organ donation and access, with emphasis on improved
regulation and public education.
PMID- 28691008
TI - Fluorescence In Situ Hybridization for Diagnosis of Whipple's Disease in Formalin
Fixed Paraffin-Embedded Tissue.
AB - Whipple's disease (WD) is a rare chronic systemic infection with a wide range of
clinical symptoms, routinely diagnosed in biopsies from the small intestine and
other tissues by periodic acid-Schiff (PAS) diastase staining and
immunohistological analysis with specific antibodies. The aim of our study was to
improve the pathological diagnosis of WD. Therefore, we analyzed the potential of
fluorescence in situ hybridization (FISH) for diagnosing WD, using a Tropheryma
(T.) whipplei-specific probe. 19 formalin-fixed paraffin-embedded (FFPE) duodenal
biopsy specimens of 12 patients with treated (6/12) and untreated (6/12) WD were
retrospectively examined using PAS diastase staining, immunohistochemistry, and
FISH. 20 biopsy specimens with normal intestinal mucosa, Helicobacter pylori, or
mycobacterial infection, respectively, served as controls. We successfully
detected T. whipplei in tissue biopsies with a sensitivity of 83% in untreated
(5/6) and 40% in treated (4/10) cases of WD. In our study, we show that FISH
based diagnosis of individual vital T. whipplei in FFPE specimens is feasible and
can be considered as ancillary diagnostic tool for the diagnosis of WD in FFPE
material. We show that FISH not only detect active WD but also be helpful as an
indicator for the efficiency of antibiotic treatment and for detection of
recurrence of disease when the signal of PAS diastase and immunohistochemistry
lags behind the recurrence of disease, especially if the clinical course of the
patient and antimicrobial treatment is considered.
PMID- 28691009
TI - Endoscopic vs. Microscopic Resection of Sellar Lesions-A Matched Analysis of
Clinical and Socioeconomic Outcomes.
AB - BACKGROUND: Direct comparisons of microscopic and endoscopic resection of sellar
lesions are scarce, with conflicting reports of cost and clinical outcome
advantages. OBJECTIVE: To determine if the proposed benefits of endoscopic
resection are realized on a population level. METHODS: We performed a matched
cohort study of 9,670 adult patients in the MarketScan database who underwent
either endoscopic or microscopic surgery for sellar lesions. Coarsened matching
was applied to estimate the effects of surgical approach on complication rates,
length of stay (LOS), costs, and likelihood of postoperative radiation. RESULTS:
We found that LOS, readmission, and revision rates did not differ significantly
between approaches. The overall complication rate was higher for endoscopy (47%
compared to 39%, OR 1.37, 95% CI 1.22-1.53). Endoscopic approach was associated
with greater risk of neurological complications (OR 1.32, 95% CI 1.11-1.55),
diabetes insipidus (OR 1.65, 95% CI 1.37-2.00), and cerebrospinal fluid
rhinorrhea (OR 1.83, 95% CI 1.07-3.13) compared to the microscopic approach.
Although the total index payment was higher for patients receiving endoscopic
resection ($32,959 compared to $29,977 for microscopic resection), there was no
difference in long-term payments. Endoscopic surgery was associated with
decreased likelihood of receiving post-resection stereotactic radiosurgery (OR
0.67, 95% CI 0.49-0.90) and intensity-modulated radiation therapy (OR 0.78, 95%
CI 0.65-0.93). CONCLUSION: Our results suggest that the transition from a
microscopic to endoscopic approach to sellar lesions must be subject to careful
evaluation. Although there are evident advantages to transsphenoidal endoscopy,
our analysis suggests that the benefits of the endoscopic approach are yet to be
materialized.
PMID- 28691010
TI - Management of Chordoma and Chondrosarcoma with Fractionated Stereotactic
Radiotherapy.
AB - OBJECTIVE: To evaluate the efficacy and toxicity of fractionated stereotactic
radiotherapy (FSRT) for chordoma and chondrosarcoma. METHODS: Twenty consecutive
patients with a histopathologic diagnosis of chordoma (n = 16) or chondrosarcoma
(n = 4) treated between 2010 and 2016 were retrospectively identified. All
patients underwent FSRT in five fractions to a median dose of 37.5 Gy (range: 25
40 Gy) and followed with serial magnetic resonance imaging. Overall survival
(OS), local recurrence-free survival (LRFS), and event-free survival (EFS) were
estimated using the Kaplan-Meier method. RESULTS: With a median follow-up of 28
months after FSRT and 40 months after initial surgery, crude OS and LRFS were
90%. Nine patients (45%) reported grade 1-3 acute toxicity, and two patients
(10%) experienced grade 4, 5 late toxicity. One patient previously treated with
proton therapy died from radiation vasculopathy 9 months after FSRT. The use of
FSRT for recurrent disease or in patients with prior radiation therapy was
associated with significantly decreased EFS. CONCLUSION: FSRT for chordoma and
chondrosarcoma is associated with high rates of OS and local control. Although
many patients experience acute toxicity, there is a low incidence of late
toxicity or irreversible treatment related morbidity despite the frequency of
prior radiotherapy in this population. FSRT is an effective adjuvant or salvage
treatment for chordoma and chondrosarcoma.
PMID- 28691011
TI - Diversity of Antimicrobial Resistance Phenotypes in Salmonella Isolated from
Commercial Poultry Farms.
AB - Salmonella remains the leading cause of foodborne illness in the United States,
and the dissemination of drug-resistant Salmonellae through the food chain has
important implications for treatment failure of salmonellosis. We investigated
the ecology of Salmonella in integrated broiler production in order to understand
the flow of antibiotic susceptible and resistant strains within this system. Data
were analyzed from a retrospective study focused on antimicrobial resistant
Salmonella recovered from commercial broiler chicken farms conducted during the
initial years of the US FDA's foray into retail meat surveillance by the National
Antimicrobial Resistance Monitoring System (NARMS). Sixty-three percentage of
Salmonella were pan-susceptible to a panel of 19 antimicrobials used by the NARMS
program. Twenty-five antimicrobial resistance phenotypes were observed in
Salmonella isolated from two broiler chicken farms. However, Salmonella
displaying resistance to streptomycin, alone, and in combination with other
antibiotics was the most prevalent (36.3%) antimicrobial resistance phenotype
observed. Resistance to streptomycin and sulfadimethoxine appeared to be linked
to the transposon, Tn21. Combinations of resistance against streptomycin,
gentamicin, sulfadimethoxine, trimethoprim, and tetracycline were observed for a
variety of Salmonella enterica serovars and genetic types as defined by pulsed
field gel electrophoresis. There were within and between farm differences in the
antibiotic susceptibilities of Salmonella and some of these differences were
linked to specific serovars. However, farm differences were not linked to
antibiotic usage. Analysis of the temporal and spatial distribution of the
endemic Salmonella serovars on these farms suggests that preventing vertical
transmission of antibiotic-resistant Salmonella would reduce carcass
contamination with antibiotic-resistant Salmonella and subsequently human risk
exposure.
PMID- 28691012
TI - Staphylococcus aureus Nasal Colonization Differs among Pig Lineages and Is
Associated with the Presence of Other Staphylococcal Species.
AB - : Staphylococcus aureus is a common colonizer in pigs, with methicillin-resistant
S. aureus (MRSA) in particular being a potential health risk to humans. To reduce
the exposure to humans, the colonization in pigs should be reduced. The aim of
this study was to quantitatively compare the susceptibility of pig lineages for
S. aureus colonization, and if the absence of S. aureus could be associated with
the presence or absence of other staphylococcal species. Nasal samples (n = 129)
were obtained from seven different pig lineages in the Netherlands, France, and
Germany. S. aureus and other staphylococci were enumerated from these samples by
real-time (RT)-PCR and culture. Associations were explored between the presence
of S. aureus and other staphylococci. S. aureus was detected by RT-PCR on all
farms and in samples from pigs of all lineages. Twenty-five percent of the pigs
from lineage F (from two farms) were colonized with S. aureus, while in all other
lineages it was more than 50% (p < 0.01). Moreover, in S. aureus-positive samples
from pigs of lineage F smaller amounts of S. aureus were found than in other
lineages. Staphylococcus sciuri, Staphylococcus cohnii, and Staphylococcus
saprophyticus were usually not found in combination with S. aureus in these
samples. IN CONCLUSION: (i) pigs from different genetic lineages have different
susceptibilities for colonization with S. aureus. These pigs might contain a
genetic factor influencing nasal colonization. (ii) Colonization of S. aureus is
also associated with the absence of S. sciuri, S. cohnii, or S. saprophyticus.
(iii) The farm environment seems to influence the presence of S. aureus in pigs.
PMID- 28691013
TI - Identification of Pharmacologically Tractable Protein Complexes in Cancer Using
the R-Based Network Clustering and Visualization Program MCODER.
AB - Current multiomics assay platforms facilitate systematic identification of
functional entities that are mappable in a biological network, and computational
methods that are better able to detect densely connected clusters of signals
within a biological network are considered increasingly important. One of the
most famous algorithms for detecting network subclusters is Molecular Complex
Detection (MCODE). MCODE, however, is limited in simultaneous analyses of
multiple, large-scale data sets, since it runs on the Cytoscape platform, which
requires extensive computational resources and has limited coding flexibility. In
the present study, we implemented the MCODE algorithm in R programming language
and developed a related package, which we called MCODER. We found the MCODER
package to be particularly useful in analyzing multiple omics data sets
simultaneously within the R framework. Thus, we applied MCODER to detect
pharmacologically tractable protein-protein interactions selectively elevated in
molecular subtypes of ovarian and colorectal tumors. In doing so, we found that a
single molecular subtype representing epithelial-mesenchymal transition in both
cancer types exhibited enhanced production of the collagen-integrin protein
complex. These results suggest that tumors of this molecular subtype could be
susceptible to pharmacological inhibition of integrin signaling.
PMID- 28691014
TI - Drug Target Protein-Protein Interaction Networks: A Systematic Perspective.
AB - The identification and validation of drug targets are crucial in biomedical
research and many studies have been conducted on analyzing drug target features
for getting a better understanding on principles of their mechanisms. But most of
them are based on either strong biological hypotheses or the chemical and
physical properties of those targets separately. In this paper, we investigated
three main ways to understand the functional biomolecules based on the
topological features of drug targets. There are no significant differences
between targets and common proteins in the protein-protein interactions network,
indicating the drug targets are neither hub proteins which are dominant nor the
bridge proteins. According to some special topological structures of the drug
targets, there are significant differences between known targets and other
proteins. Furthermore, the drug targets mainly belong to three typical
communities based on their modularity. These topological features are helpful to
understand how the drug targets work in the PPI network. Particularly, it is an
alternative way to predict potential targets or extract nontargets to test a new
drug target efficiently and economically. By this way, a drug target's homologue
set containing 102 potential target proteins is predicted in the paper.
PMID- 28691015
TI - "mTOR Signaling Pathway": A Potential Target of Curcumin in the Treatment of
Spinal Cord Injury.
AB - The purpose of this review is to discuss the possibility of the treatment of
spinal cord injury (SCI) with curcumin via regulating the mTOR signaling pathway,
which may provide another strong support for curcumin to be a promising medicine
applied to the treatment of SCI. Curcumin is termed as a multifunctional
targeting therapy drug that regulates the mTOR signaling pathway in the treatment
of numerous diseases. Previous research has already revealed that mTOR signaling
pathway plays a vital role in prognosis, which involves the axon regeneration and
autophagy. This review discusses a potential mechanism that curcumin suppresses
the activation of this pathway and ameliorates the microenvironment of axons
regeneration which would provide a new way that induces autophagy appropriately.
PMID- 28691016
TI - Analysis and Modeling for Big Data in Cancer Research.
PMID- 28691017
TI - Reduction of the Oxidative Stress Status Using Steviol Glycosides in a Fish Model
(Cyprinus carpio).
AB - Steviol glycosides are sweetening compounds from the Stevia rebaudiana Bertoni
plant. This product is considered safe for human consumption and was approved as
a food additive by the Food and Drugs Administration (FDA) and European Food
Safety Authority (EFSA). Its effects on the ecosystem have not been studied in
depth; therefore, it is necessary to carry out ecotoxicological studies in
organisms such as Cyprinus carpio. The present study aimed to evaluate the
antioxidant activity by SGs on diverse tissues in C. carpio using oxidative
stress (OS) biomarkers. To test the antioxidant activity, carps were exposed to
four systems: (1) SGs free control, (2) CCl4 0.5 mL/kg, (3) SGs 1 g/L, and (4)
CCl4 0.5 mL/kg + SGs 1 g/L at 96 h. The following biomarkers were analyzed:
lipoperoxidation (LPX), hydroperoxide content (HPC), and protein carbonyl content
(PCC), as well as antioxidant activity of superoxide dismutase (SOD) and catalase
(CAT). It was found that both (3 and 4) systems' exposure decreases LPX, CHP,
PCC, SOD, and CAT with respect to the CCl4 system. The results of this study
demonstrate that the concentrations of SGs used are not capable of generating
oxidative stress and, on the contrary, would appear to induce an antioxidant
effect.
PMID- 28691018
TI - Genetic Variants in the Promoter Region of miR-10b and the Risk of Breast Cancer.
AB - Variants in microRNA genes may affect their expression by interfering with the
microRNA maturation process and may substantially contribute to the risk of
breast cancer. Recent studies have identified miR-10b as an interesting candidate
because of its close association with the metastatic behavior of breast cancer.
However, the roles of miR-10b-related single nucleotide polymorphisms in breast
cancer susceptibility remain unclear. This case-control study evaluated the
associations between variants in the upstream transcription regulation region of
miR-10b and the risk of breast cancer among Chinese women. Seven potentially
functional SNPs were investigated using genotyping assays. The potential
biological functions of the identified positive SNPs were further evaluated using
in silico databases. We found that rs4078756, which was located at the promoter
region of miR-10b, was significantly associated with breast cancer risk
(rs4078756 AG/GG versus AA, adjusted odds ratio: 1.17, 95% confidence interval:
1.02-1.35). The other six single nucleotide polymorphisms exhibited negative
associations. Based on the in silico prediction, rs4078756 potentially regulated
miR-10b expression through promoter activation or repression. These findings
indicate that a potentially functional SNP (rs4078756) in the promoter region of
miR-10b may contribute to breast cancer susceptibility among Chinese women.
PMID- 28691019
TI - Fish Oil Feeding Modulates the Expression of Hepatic MicroRNAs in a Western-Style
Diet-Induced Nonalcoholic Fatty Liver Disease Rat Model.
AB - Nonalcoholic fatty liver disease (NAFLD) is one of the most prevalent chronic
liver diseases worldwide. Recent studies have indicated that fish oil
supplementation has benefits against NAFLD. Our previous transcriptomic study has
validated the effect of fish oil supplementation on altering hepatic gene
expression in a NAFLD rat model. In the current study, we examined the effects of
fish oil on the expression of hepatic microRNAs. Male Sprague-Dawley rats were
fed with a lab chow (CON), high-fat high-cholesterol diet (WD), or WD
supplemented with fish oil (FOH), respectively. Small RNAs were extracted from
livers for RNA-sequencing. A total of 79 miRNAs were identified as differentially
expressed miRNAs (DEMs) between FOH and WD groups, exemplified by rno-miR-29c-3p,
rno-miR-30d-5p, rno-miR-33-5p, rno-miR-34a, and rno-miR-328a-3p. Functional
annotation of DEMs predicted target genes suggested that the altered hepatic
miRNAs contributed to fish oil modification of hepatic lipid metabolism and
signaling transduction. Integrative analysis of DEMs and differentially expressed
genes suggested that the expression difference of Pcsk9, Insig2, Per3, and
Socs1/3 between FOH and WD groups may be due to miRNA modification. Our study
reveals that fish oil supplementation alters hepatic expression of miRNAs, which
may contribute to fish oil amelioration of NAFLD in rats.
PMID- 28691020
TI - miR-200c Accelerates Hepatic Stellate Cell-Induced Liver Fibrosis via Targeting
the FOG2/PI3K Pathway.
AB - BACKGROUND: Although expression of miR-200s is aberrant in liver fibrosis, its
role in liver fibrogenesis still remains unknown. Here, we investigated the role
of miR-200c in the activation of human hepatic stellate cells (HSCs) and
induction of liver fibrosis. METHODS: We engineered human HSCs (LX2 cell line) to
stably express miR-200c (LX2-200c) or empty vector control (LX2-nc). RESULTS: miR
200c expression upregulated alpha-smooth muscle actin (SMA) and vimentin,
enhanced HSCs growth and migration, increased expression of collagen type I (a
main component of ECM) gene and secretion of epidermal growth factor (EGF), and
upregulated the phosphorylation of Akt, a downstream effector of the PI3K
pathway. As a target of miR-200s and inhibitor of PI3K pathway, FOG2 protein
expression was significantly suppressed in LX2-200c cells. Moreover, LY294002, a
highly selective inhibitor of PI3K, blocked phosphorylation of Akt and the
effects of miR-200c. CONCLUSIONS: These data suggest that miR-200c activates HSCs
in liver fibrosis possibly by downregulating FOG2 protein expression and
upregulating PI3K/Akt signaling. Autocrine activation of EGF signaling may also
be a mechanism of miR-200c-mediated HSCs activation. So miR-200c can be a
potential marker for HSCs activation and liver fibrosis progression, as well as a
potential target to attenuate liver fibrosis.
PMID- 28691021
TI - Evaluation of Stability and In Vitro Security of Nanoemulsions Containing
Eucalyptus globulus Oil.
AB - Essential oil of Eucalyptus globulus presents several pharmacological properties.
However, their therapeutic efficacy may be affected by limitations due to several
conditions, rendering it difficult to obtain stable and effective pharmaceutical
formulations. The use of nanotechnology is an alternative to improve their
characteristics aiming to ensure their stability and effectiveness. Furthermore,
studies about the possible toxic effects of nanostructures are necessary to
evaluate safety when the formulation comes into contact with human cells. Hence,
in this paper, we evaluate for the first time the stability and in vitro
cytogenotoxicity of nanoemulsions containing Eucalyptus globulus in peripheral
blood mononuclear cells. As a result, the stability study found that the best
condition for storage up to 90 days was refrigeration (4 degrees C); it was the
condition that best preserved the nanometric features. The content of the major
compounds of oil was maintained after nanoencapsulation and preserved over time.
In tests to evaluate the safety of this formulation, we can conclude that, at a
low concentration (approximately 0.1%), Eucalyptus globulus nanoemulsion did not
cause toxicity in peripheral blood mononuclear cells and also showed a protective
effect in cells against possible damage when compared to oil in free form.
PMID- 28691022
TI - Purification and Characterization of an ATPase GsiA from Salmonella enterica.
AB - The coding sequence of Salmonella enterica gsiA was cloned and expressed in E.
coli. The protein was purified and ATPase activity was characterized by NADH
oxidation method. GsiA exhibited optimum activity at 30 degrees C and at pH 8 in
Tris/HCl buffer. GsiA protein was stable at 20 degrees C. 66% and 44% activity
remained after incubation at 30 degrees C and 40 degrees C for 30 min. pH 7 and
pH 9 incubation would obviously reduce the ATPase activity. In vivo functionality
of gsiA was determined by constructing gene deletion strains. gsiA was shown to
be essential for GSI mediated glutathione uptake and gsiA deletion could decrease
the virulence of Salmonella enterica. Interactions of glutathione import proteins
GsiA, GsiB, GsiC, and GsiD were investigated by using bacterial two-hybrid
system. GsiA could interact with itself and inner membrane proteins GsiC and
GsiD. This report provides the first description of gsiA functions in Salmonella
enterica. The results could help elucidating the glutathione uptake mechanism and
glutathione functions in bacteria.
PMID- 28691023
TI - Iron Homeostasis in Tissues Is Affected during Persistent Chlamydia pneumoniae
Infection in Mice.
AB - Chlamydia pneumoniae (C. pneumoniae) may be a mediator in the pathogenesis of
atherosclerosis. For its growth C. pneumoniae depends on iron (Fe), but how Fe
changes in tissues during persistent infection or affects bacterial replication
in tissues is unknown. C. pneumoniae-infected C57BL/6J mice were sacrificed on
days 4, 8, 20, and 40. Mice had bacteria in the lungs and liver on all days.
Inflammatory markers, chemokine Cxcl2 and interferon-gamma, were not affected in
the liver on day 40. The copper (Cu)/zinc (Zn) ratio in serum, another marker of
infection/inflammation, increased on day 4 and tended to increase again on day
40. The Fe markers, transferrin receptor (TfR), Hepcidin (Hamp1), and ferroportin
1 (Fpn1), increased in the liver on day 4 and then normalized except for TfR that
tended to decrease. TfR responses were similar to Fe in serum that increased on
day 4 but tended to decrease thereafter. In the liver, Fe was increased on day 4
and also on day 40. The reappearing increases in Cu/Zn on day 40 concomitant with
the increase in liver Fe on day 40, even though TfR tended to decrease, and the
fact that viable C. pneumoniae was present in the lungs and liver may indicate
the early phase of activation of recurrent infection.
PMID- 28691024
TI - Self-Assembling RADA16-I Peptide Hydrogel Scaffold Loaded with Tamoxifen for
Breast Reconstruction.
AB - More and more breast cancer patients prefer autologous fat tissue transfer
following lumpectomy to maintain perfect female characteristics. However, the
outcome was not satisfactory due to the transplanted fat absorption. In this
study, we prepared two RADA16-I peptide scaffolds with and without tamoxifen.
Both scaffolds were transparent, porous, and hemisphere-shaped. The hADSCs
isolated from liposuction were attached to the scaffold. The growth inhibition of
the hADSCs induced by TAM in 2-demensional (2D) culture was higher than that in
TAM-loaded hydrogel scaffold 3D culture (P < 0.05); however, the same outcomes
were not observed in MCF-7 cells. Correspondingly, the apoptosis of the hADSCs
induced by TAM was significantly increased in 2D culture compared to that in
scaffold 3D culture (P < 0.05). Yet the outcomes of the aoptosis in MCF-7 were
contrary. Apoptosis-related protein Bcl-2 was involved in the process. In vivo
experiments showed that both scaffolds formed a round mass after subcutaneous
implantation and it retained its shape after being pressed slightly. The
implantation had no effect on the weight and activity of the animals. The results
suggested that TAM-loaded RADA16-I hydrogel scaffolds both provide support for
hADSCs cells attachment/proliferation and retain cytotoxic effect on MCF-7 cells,
which might be a promising therapeutic breast tissue following lumpectomy.
PMID- 28691025
TI - Protective and Predisposing Morphological Factors in Suprascapular Nerve
Entrapment Syndrome: A Fundamental Review Based on Recent Observations.
AB - Suprascapular nerve entrapment syndrome (SNES) is a neuropathy caused by
compression of the nerve along its course. The most common compression sites
include the suprascapular notch and the spinoglenoid notch. The aim of this
article was to review the anatomical factors influencing the occurrence of SNES
in the light of the newest reports. Potential predisposing morphological factors
include a V-shaped, narrow, or "deep" suprascapular notch; a band-shaped,
bifurcated, or completely ossified superior transverse scapular ligament (STSL);
particular arrangements of the suprascapular nerve and vessels at the
suprascapular notch. A very recent report indicates structures at the
suprascapular notch region that may protect from SNES, such as the suprascapular
notch veins (SNV). The role of the anterior coracoscapular ligament (ACSL) is
still not clear. While some studies indicate that it may predispose for SNES, the
newest study proposes a protective function. Knowledge of these variations is
essential for arthroscopic and other surgical procedures of this area in order to
avoid iatrogenic injury of the suprascapular nerve or unexpected bleeding from
the suprascapular vessels running alongside the STSL.
PMID- 28691026
TI - Quercetin Attenuates Vascular Calcification through Suppressed Oxidative Stress
in Adenine-Induced Chronic Renal Failure Rats.
AB - BACKGROUND: This study investigated whether quercetin could alleviate vascular
calcification in experimental chronic renal failure rats induced by adenine.
METHODS: 32 adult male Wistar rats were randomly divided into 4 groups fed normal
diet, normal diet with quercetin supplementation (25 mg/kg.BW/d), 0.75% adenine
diet, or adenine diet with quercetin supplementation. All rats were sacrificed
after 6 weeks of intervention. Serum renal functions biomarkers and oxidative
stress biomarkers were measured and status of vascular calcification in aorta was
assessed. Furthermore, the induced nitric oxide synthase (iNOS)/p38 mitogen
activated protein kinase (p38MAPK) pathway was determined to explore the
potential mechanism. RESULTS: Adenine successfully induced renal failure and
vascular calcification in rat model. Quercetin supplementation reversed
unfavorable changes of phosphorous, uric acid (UA) and creatinine levels,
malonaldehyde (MDA) content, and superoxide dismutase (SOD) activity in serum and
the increases of calcium and alkaline phosphatase (ALP) activity in the aorta (P
< 0.05) and attenuated calcification and calcium accumulation in the medial layer
of vasculature in histopathology. Western blot analysis showed that iNOS/p38MAPK
pathway was normalized by the quercetin supplementation. CONCLUSIONS: Quercetin
exerted a protective effect on vascular calcification in adenine-induced chronic
renal failure rats, possibly through the modulation of oxidative stress and
iNOs/p38MAPK pathway.
PMID- 28691027
TI - Hand Hygiene Practices and Microbial Investigation of Hand Contact Swab among
Physiotherapists in an Ebola Endemic Region: Implications for Public Health.
AB - BACKGROUND: Hand hygiene practices (HHP), as a critical component of infection
prevention/control, were investigated among physiotherapists in an Ebola endemic
region. METHOD: A standardized instrument was administered to 44 randomly
selected physiotherapists (23 males and 21 females), from three tertiary
hospitals in Enugu, Nigeria. Fifteen participants (aged 22-59 years) participated
in focus group discussions (FGDs) and comprised 19 participants in a subsequent
laboratory study. After treatment, the palms/fingers of physiotherapists were
swabbed and cultured, then incubated aerobically overnight at 37 degrees C, and
examined for microbial growths. An antibiogram of the bacterial isolates was
obtained. RESULTS: The majority (34/77.3%) of physiotherapists were aware of the
HHP protocol, yet only 15/44.1% rated self-compliance at 71-100%. FGDs identified
forgetfulness/inadequate HHP materials/infrastructure as the major barriers to
HHP. Staphylococcus aureus were the most prevalent organisms, prior to (8/53.33%)
and after (4/26.67%) HPP, while Pseudomonas spp. were acquired thereafter. E.
coli were the most antibiotic resistant microbes but were completely removed
after HHP. Ciprofloxacin and streptomycin were the most effective antibiotics.
CONCLUSION: Poor implementation of HPP was observed due to inadequate
materials/infrastructure/poor behavioral orientation. Possibly, some HPP
materials were contaminated; hence, new microbes were acquired. Since HPP removed
the most antibiotic resistant microbes, it might be more effective in infection
control than antibiotic medication.
PMID- 28691028
TI - Production of a Functional Frozen Yogurt Fortified with Bifidobacterium spp.
AB - Frozen dairy products have characteristics of both yogurt and ice cream and could
be the persuasive carriers of probiotics. Functions of the frozen yogurt
containing viable bifidobacterial cells are recognized and favored by the people
of all ages. We developed a kind of yogurt supplemented by Bifidobacterium
species. Firstly, five strains of Bifidobacterium spp. (Bifidobacterium bifidum
ATCC 11547, Bifidobacterium longum ATCC 11549, Bifidobacterium infantis ATCC
11551, Bifidobacterium adolescentis ATCC 11550, and Bifidobacterium breve ATCC
11548) were evaluated based on the feasibility criteria of probiotics, comprising
acid production, bile tolerance, and adhesion to epithelial cells. Formerly, we
combined the optimum strains with yogurt culture (Lactobacillus delbrueckii
subsp. bulgaricus EMCC 11102 and Streptococcus salivarius subsp. thermophilus
EMCC 11044) for producing frozen yogurt. Finally, physiochemical properties and
sensory evaluation of the frozen yogurt were investigated during storage of 60
days at -18 degrees C. Results directed that Bifidobacterium adolescentis ATCC
11550 and Bifidobacterium infantis ATCC 11551 could be utilized with yogurt
culture for producing frozen yogurt. Moreover, the frozen yogurt fermented by two
bifidobacterial strains and yogurt culture gained the high evaluation in the
physiochemical properties and sensory evaluation. In summary, our results
revealed that there was no significant difference between frozen yogurt fermented
by Bifidobacterium spp. and yogurt culture and that fermented by yogurt culture
only.
PMID- 28691029
TI - Laparoscopic Pyeloplasty for Ureteropelvic Junctions Obstruction in Adults: 6
Years' Experience in One Center.
AB - OBJECTIVE: Ureteropelvic junction obstruction (UPJO) is a common cause of
symptomatic ureteral obstruction. The aim of this study is to assess the outcome
of laparoscopic pyeloplasty in patients with UPJO. PATIENTS AND METHODS: Medical
reports of 47 UPJO patients treated with laparoscopic pyeloplasty were
retrospectively analysed. All patients were recruited from our center in the
period 2004-2011. RESULTS: We evaluated 47 patients. Mean age was 36 years and
mean hospital stay 3.6 days. 42 (79%) of the patients had pain and 46 (98%) were
diagnosed with hydronephrosis. 19 patients (40%) had a renal function below 40%
of the affected kidney and 49% had impaired renal scan drainage. Postoperative
significant improvement in pain score and renal scan drainage was found in 92%
and 47% of the patients, respectively. Improvement of renal function > 10% was
found in 11 patients (23%); the function remained stable in 31 patients (66%) and
deteriorated > 10% in 5 patients (11%). We found no correlation between sex or
age and the outcome. CONCLUSION: Laparoscopic pyeloplasty for UPJO leads to
relief of pain and preserved or improved renal function in the majority of the
patients. Overall laparoscopic pyeloplasty is an efficient treatment for UPJO.
PMID- 28691030
TI - A Novel Capillary Electrophoresis-Based High-Throughput Multiplex Polymerase
Chain Reaction System for the Simultaneous Detection of Nine Pathogens in Swine.
AB - Here we aimed to develop a capillary electrophoresis-based high-throughput
multiplex polymerase chain reaction (PCR) system for the simultaneous detection
of nine pathogens in swine. Nine pairs of specific primers and a set of universal
primers were designed; the multiplex PCR was established. The specificity and
cross-reactivity of this assay were examined, and the detection limit was
determined using serial 10-fold dilutions of plasmids containing the target
sequences. The assay was further tested using 144 clinical samples. We found that
the nine specific amplification peaks were observed, and the assay had a high
degree of specificity, without nonspecific amplification. The simultaneous
detection limit for the nine viruses reached 10000 copies MUL-1 when all of the
premixed viral targets were present. Seventy-seven of the clinical samples tested
positive for at least one of the viruses; the principal viral infections in the
clinical samples were porcine circovirus type 2 and porcine reproductive and
respiratory syndrome virus. This approach has much potential for further
development of high-throughput detection tools for the diagnosis of diseases in
animals.
PMID- 28691031
TI - In Vitro Plant Regeneration from Commercial Cultivars of Soybean.
AB - Soybean, a major legume crop, is the source of vegetable oil and protein. There
is a need for transgenic approaches to breeding superior soybean varieties to
meet future climate challenges. Efficient plant regeneration is a prerequisite
for successful application of genetic transformation technology. Soybean
cultivars are classified into different maturity groups based on photoperiod
requirements. In this study, nine soybean varieties belonging to different
maturity group were regenerated successfully from three different explants: half
split hypocotyl, complete hypocotyl, and cotyledonary node. All the genotypes and
explant types responded by producing adventitious shoots. Shoot induction
potential ranged within 60-87%, 50-100%, and 75-100%, and regeneration rate
ranged within 4.2-10, 2.7-4.2, and 2.6-10.5 shoots per explant using half split
hypocotyl, complete hypocotyl, and cotyledonary explants, respectively, among all
the tested genotypes. Bunya variety showed the best regeneration response using
half split and complete hypocotyl explants and the PNR791 with cotyledonary node.
The regenerated shoots were successfully rooted and acclimatized to glasshouse
conditions. This study shows that commercial varieties of soybean are amenable to
shoot regeneration with high regeneration frequencies and could be exploited for
genetic transformation. Further, our results show no correlation between shoots
regeneration capacity with the maturity grouping of the soybean cultivars tested.
PMID- 28691032
TI - Jugular Venous Reflux Is Associated with Perihematomal Edema after Intracerebral
Hemorrhage.
AB - The purpose of this study was to determine whether jugular venous reflux (JVR) is
associated with perihematomal edema (PHE) in individuals with intracerebral
hemorrhage (ICH). Patients with spontaneous supratentorial ICH within 72 h of
symptom onset were enrolled. Baseline brain computed tomography (CT) scan was
performed, with a follow-up CT examination at 12 +/- 3 days after onset. Jugular
venous color Doppler ultrasound was performed at 12 +/- 3 days after onset to
examine the JVR status. A total of 65 patients with ICH were enrolled. In
logistic regression analysis, absolute PHE volume was significantly associated
with JVR (OR, 5.46; 95% CI, 1.04-28.63; p = 0.044) and baseline hematoma volume
(OR, 1.14; 95% CI, 1.03-1.26; p = 0.009) within 72 h of onset. It was also
correlated with JVR (OR, 15.32; 95% CI, 2.52-92.99; p = 0.003) and baseline
hematoma volume (OR, 1.14; 95% CI, 1.04-1.24; p = 0.006) at 12 +/- 3 days after
onset. In a similar manner, relative PHE volume was significantly associated with
JVR (OR, 14.85; 95% CI, 3.28-67.17; p < 0.001) within 72 h of onset and at 12 +/-
3 days after onset (OR, 5.87; 95% CI, 1.94-17.77; p = 0.002). JVR is associated
with both absolute and relative PHE volumes after ICH.
PMID- 28691033
TI - Prevalence of Toxoplasma gondii and Other Gastrointestinal Parasites in Domestic
Cats from Households in Thika Region, Kenya.
AB - Gastrointestinal (GIT) parasites of domestic cats (Felis catus) not only cause
morbidity but are also potential zoonotic agents. The current study aimed at
establishing the prevalence of GIT parasites in cats kept by households in Thika
region, Kenya. Fecal samples were collected randomly from 103 cats and analyzed
for presence of parasites using standard parasitological methods. In descending
order, the prevalence of the detected protozoa parasites was Isospora spp. 43.7%
(95% CI: 40.4-47%), Cryptosporidium spp. 40.8% (95% CI: 37.5-44.1%), Toxoplasma
gondii 7.8% (95% CI: 4.5-11.1%), and Entamoeba spp. 2.9% (95% CI: 1.6-6.2%). The
prevalence of the observed helminths was Strongyloides stercoralis 43.7% (95% CI:
40.4-47%), Toxocara cati 23.3% (95% CI: 20-26.6%), Ancylostoma spp. 9.7% (95% CI:
6.4-13%), Dipylidium caninum 8.7% (95% CI: 5.4-12.0%), and Acanthocephala spp.
1.9% (95% CI: 1-4.2%). The percentage of cats excreting at least one species of
parasite was 73.2% (95% CI = 69.9-76.5%). The study shows that the cats have high
spectrum (9) of parasites which are known to affect the cat's health and some are
of zoonotic significance.
PMID- 28691034
TI - The Effects of Time Lag and Cure Rate on the Global Dynamics of HIV-1 Model.
AB - In this research article, a new mathematical model of delayed differential
equations is developed which discusses the interaction among CD4 T cells, human
immunodeficiency virus (HIV), and recombinant virus with cure rate. The model has
two distributed intracellular delays. These delays denote the time needed for the
infection of a cell. The dynamics of the model are completely described by the
basic reproduction numbers represented by R0, R1, and R2. It is shown that if R0
< 1, then the infection-free equilibrium is locally as well as globally stable.
Similarly, it is proved that the recombinant absent equilibrium is locally as
well as globally asymptotically stable if 1 < R0 < R1. Finally, numerical
simulations are presented to illustrate our theoretical results. Our obtained
results show that intracellular delay and cure rate have a positive role in the
reduction of infected cells and the increasing of uninfected cells due to which
the infection is reduced.
PMID- 28691035
TI - Corneal Collagen Cross-Linking for Keratoconus: Systematic Review.
AB - PURPOSE: To evaluate the efficacy of collagen cross-linking (CXL) one year after
treatment for keratoconus compared to no treatment by summarizing randomized
controlled trials (RCTs) using a systematic review. METHODS: Trials meeting the
selection criteria were quality appraised, and the data were extracted by two
independent authors. The outcome parameters included maximum keratometry (Kmax),
corneal thickness at the thinnest point, best spectacle-corrected visual acuity
(BSCVA), uncorrected visual acuity (UCVA), spherical equivalent (SE) refraction,
and cylindrical refraction one year after CXL. We compared the changes in the
above parameters with the control group. RESULTS: We identified five RCTs
involving 289 eyes that met the eligibility criteria for this systematic review.
The changes in BSCVA from baseline to one year exhibited a significant difference
between the two groups. There was no statistically significant difference between
the two groups for changes in corneal thickness and cylindrical refraction. We
did not conduct a meta-analysis in Kmax, UCVA, and SE refraction because their I2
values were greater than 50%. CONCLUSIONS: According to the systematic review,
CXL may be effective in halting the progression of keratoconus for one year under
certain conditions, although evidence is limited due to the significant
heterogeneity and paucity of RCTs.
PMID- 28691036
TI - Detection of Secondary Causes and Coexisting Diseases in Hypertensive Patients:
OSA and PA Are the Common Causes Associated with Hypertension.
AB - BACKGROUND: Since the control rate of blood pressure is lower in mainland China,
the aim of this study is to investigate the proportion of secondary causes and
coexisting diseases of hypertension in hypertensive patients. METHODS: Data on
consecutive patients with hypertension who visited the Hypertension Center.
Diseases were detected using an established strict screening protocol. RESULTS:
Detection rate of secondary causes and coexisting diseases of hypertension was
39.5% among 3003 hypertensive patients. Obstructive sleep apnea (OSA) was the
most common, accounting for 24.7% of patients, followed by primary aldosteronism
(PA) (5.8%) and PA + OSA (4.9%). Endocrine hypertension accounted for 12.1% of
patients, including 10.7% of patients with PA, 1.1% with hypothyroidism, 0.1%
with pheochromocytoma, 0.1% with Cushing's syndrome, and 0.1% with
hyperthyroidism, respectively. Those who smoke, those who are obese, and those
who have diabetes accounted for 31.3%, 27.5%, and 16.6% of total patients,
respectively. There were overlapping conditions in secondary causes and
coexisting diseases of hypertension. OSA was the most common in each age- and BMI
stratified group. CONCLUSION: Findings from the current study suggest an
increasing frequency of secondary forms of hypertension, highlighting the burden
of OSA and PA in hypertensive patients.
PMID- 28691038
TI - Establishing a treatment protocol for concomitant major burn and trauma patients:
a tropical Asian hospital's experience.
PMID- 28691039
TI - A Sensor-Based Method for Diagnostics of Machine Tool Linear Axes.
AB - A linear axis is a vital subsystem of machine tools, which are vital systems
within many manufacturing operations. When installed and operating within a
manufacturing facility, a machine tool needs to stay in good condition for parts
production. All machine tools degrade during operations, yet knowledge of that
degradation is illusive; specifically, accurately detecting degradation of linear
axes is a manual and time-consuming process. Thus, manufacturers need automated
and efficient methods to diagnose the condition of their machine tool linear axes
without disruptions to production. The Prognostics and Health Management for
Smart Manufacturing Systems (PHM4SMS) project at the National Institute of
Standards and Technology (NIST) developed a sensor-based method to quickly
estimate the performance degradation of linear axes. The multi-sensor-based
method uses data collected from a 'sensor box' to identify changes in linear and
angular errors due to axis degradation; the sensor box contains inclinometers,
accelerometers, and rate gyroscopes to capture this data. The sensors are
expected to be cost effective with respect to savings in production losses and
scrapped parts for a machine tool. Numerical simulations, based on sensor
bandwidth and noise specifications, show that changes in straightness and angular
errors could be known with acceptable test uncertainty ratios. If a sensor box
resides on a machine tool and data is collected periodically, then the
degradation of the linear axes can be determined and used for diagnostics and
prognostics to help optimize maintenance, production schedules, and ultimately
part quality.
PMID- 28691037
TI - Phagocytosis: A Fundamental Process in Immunity.
AB - One hundred years have passed since the death of Elie Metchnikoff (1845-1916). He
was the first to observe the uptake of particles by cells and realized the
importance of this process for the host response to injury and infection. He also
was a strong advocate of the role of phagocytosis in cellular immunity, and with
this he gave us the basis for our modern understanding of inflammation and the
innate and acquired immune responses. Phagocytosis is an elegant but complex
process for the ingestion and elimination of pathogens, but it is also important
for the elimination of apoptotic cells and hence fundamental for tissue
homeostasis. Phagocytosis can be divided into four main steps: (i) recognition of
the target particle, (ii) signaling to activate the internalization machinery,
(iii) phagosome formation, and (iv) phagolysosome maturation. In recent years,
the use of new tools of molecular biology and microscopy has provided new
insights into the cellular mechanisms of phagocytosis. In this review, we present
a general view of our current knowledge on phagocytosis. We emphasize novel
molecular findings, particularly on phagosome formation and maturation, and
discuss aspects that remain incompletely understood.
PMID- 28691040
TI - Flow Cytometry of Lung and Bronchoalveolar Lavage Fluid Cells from Mice
Challenged with Fluorescent Aspergillus Reporter (FLARE) Conidia.
AB - Aspergillus fumigatus is a ubiquitous fungal pathogen that forms airborne
conidia. The process of restricting conidial germination into hyphae by lung
leukocytes is critical in determining infectious outcomes. Tracking the outcome
of conidia-host cell encounters in vivo is technically challenging and an
obstacle to understanding the molecular and cellular basis of antifungal immunity
in the lung. Here, we describe a method that utilizes a genetically engineered
Aspergillus strain [called FLARE (Jhingran et al., 2012; Espinosa et al., 2014;
Heung et al., 2015)] to monitor conidial phagocytosis and killing by leukocytes
within the lung environment at single encounter resolution.
PMID- 28691041
TI - Affinity Purification of the RNA Degradation Complex, the Exosome, from HEK-293
Cells.
AB - The RNA exosome complex plays a central role in RNA processing and regulated
turnover. Present both in cytoplasm and nucleus, the exosome functions through
associations with ribonucleases and various adapter proteins (reviewed in
[Kilchert et al., 2016]). The following protocol describes an approach to purify
RNA exosome complexes from HEK-293 cells, making use of inducible ectopic
expression, affinity capture, and rate-zonal centrifugation. The obtained RNA
exosomes have been used successfully for proteomic, structural, and enzymatic
studies (Domanski et al., 2016).
PMID- 28691042
TI - High-definition-iSCAN virtual chromoendoscopy has high sensitivity and
specificity for the diagnosis of eosinophilic esophagitis.
PMID- 28691043
TI - Incidence of small bowel neoplasia in Lynch syndrome assessed by video capsule
endoscopy.
AB - BACKGROUND AND STUDY AIMS : Lynch syndrome (LS) patients have an increased risk
of small bowel cancer. The question is whether surveillance will lead to early
detection of (pre)malignant lesions. We recently reported on prevalence of small
bowel neoplasia (SBN) in LS patients as assessed by video capsule endoscopy
(VCE). The aim of this prospective study was to determine the incidence of SBN.
PATIENTS AND METHODS : Asymptomatic LS patients who underwent a VCE were invited
to undergo a second VCE procedure 2 years later. If abnormalities or polypoid
lesions larger than 1 cm were detected, subsequent endoscopic procedures were
performed. RESULTS : A total of 155 (78 %) of the initial 200 patients underwent
a second VCE procedure after a mean of 2.2 (range 1 - 6) years. In 17 of the 155
(11 %) patients possibly significant lesions were detected, which required
further investigation by means of gastroduodenoscopy (n = 8) or balloon-assisted
endoscopy (n = 9). These procedures revealed no SBN. CONCLUSION : No SBN was
found after 2 years. Surveillance of the small bowel by VCE does not seem to be
warranted in asymptomatic LS patients.
PMID- 28691044
TI - Rituals in gastrointestinal endoscopy at the crossroads of shaman and science.
AB - BACKGROUND AND AIM: Over the last decades, the length of time required for
endoscopic procedures has greatly expanded. The aim of the present decision
analysis is to study the interactions amongst various factors that have caused
such delays and to compare the relative magnitude of their influences. METHODS:
Performance of gastrointestinal endoscopy is influenced by the interaction of
five domains, that is, (1) patient discomfort and fear; (2) injury, disorder, and
disruption; (3) rituals to reduce fear, prevent disruption, and maintain order;
(4) administrators or various health providers carrying out a ritual; (5)
information, knowledge, and science, which influence fear, prevent disruption,
and curtail unnecessary ritualistic behavior. A Markov chain model is used to
describe the interaction among the five domains. RESULTS: Overall, science
exerts the strongest influence, followed by fear and ritual as distant second and
third most relevant influences, respectively. Disruption and administrator exert
only a minor influence on the system of mutual interactions. CONCLUSIONS:
Studying patterns of ritualistic behavior during endoscopy and subjecting them to
means of scientific research could help eliminate redundancy, cutting unnecessary
rituals, and thus making gastrointestinal endoscopy overall more efficient.
PMID- 28691045
TI - Pharyngocutaneous fistula as an alternative access route for inserting a
percutaneous endoscopic gastrostomy tube in head and neck cancer patients.
AB - BACKGROUND AND STUDY AIMS: Performing a percutaneous endoscopic gastrostomy
(PEG) in head and neck cancer (HNC) patients can be challenging because of the
presence of trismus, pharyngeal obstruction by tumor, and pharyngoesophageal
strictures or fistula. Pharyngocutaneous fistula (PCF) is a major postoperative
concern in patients submitted to total laryngectomy (TL). In the medical
literature to date, the cervical fistula has been used as an access to PEG in
only four reports. The aim of this study was to evaluate the safety of cervical
fistula for insertion of a PEG tube. PATIENTS AND METHODS: Retrospective study
at a single tertiary referral center, regarding the technical feasibility, safety
and outcomes of a PEG tube introduced by a cervical fistula in HNC patients with
obstructive lesions of the oropharynx. RESULTS: The procedure was technically
successful in all 21 patients. A PEG tube was used for a minimum of 1 month and a
maximum of 120 months. Twelve patients died while using the PEG tube, 8 had it
taken out because it was no longer needed, and only 1 had the tube still in use.
Adverse events occurred in 8 patients: granuloma (19 %), dermatitis (9.5 %),
accidental late removal of the tube (9.5 %), periprocedural gastric wall hematoma
(9.5 %), peristomal wound infection (4.7 %), buried bumper syndrome (4.7 %), and
traumatic gastric ulcer (4.7 %). CONCLUSION: A postoperative cervical fistula
can successfully work as a reliable and safe access for a PEG tube procedure in
HNC patients, avoiding unnecessary surgery and reducing costs.
PMID- 28691046
TI - A randomized trial comparing winged versus conventional plastic stents for
malignant bile duct strictures.
AB - BACKGROUND AND STUDY AIMS : Stent insertion at endoscopic retrograde
cholangiopancreatography (ERCP) is an established therapy for managing malignant
biliary obstruction. Conventional plastic stents with a tubular design are most
commonly used despite limited patency. Plastic stents with a winged design may
theoretically increase the duration of stent patency. The aim of this study was
to compare stent patency of the winged versus conventional plastic stents in
patients with malignant biliary obstruction. PATIENTS AND METHODS : A
prospective, randomized subject-blinded trial was conducted. Patients with
malignant biliary obstruction were randomized (1:1) to either a 10 French winged
stent or 7 or 10 French conventional plastic stent. Strictures greater than 1 cm
distal to the hilum were included. Patients were followed clinically to determine
the frequency of stent failure until surgery, death or study closure. RESULTS :
Fifty-eight patients were enrolled. Following 9 exclusions, 49 patients were
randomized to a winged (n = 23) or conventional stent (n = 26). Median time to
stent failure was 89 (95 % CI 26-NA) vs 143 (95 % CI 33 - 266) days ( P = 0.963)
for the winged and conventional group, respectively. Stent failure for the winged
group occurred in 11 (48 %) compared to 14 (54 %) in the conventional group.
Median survival was 123 (95 % CI 81 - 189) vs 342 days (95 % CI 123 - 704) (p =
0.084) in the winged and conventional group respectively. There were no procedure
related adverse events. CONCLUSIONS : Improvement in stent patency was not seen
with the winged stent when compared to the conventional plastic stent.
PMID- 28691047
TI - Location of colorectal cancer: colonoscopy versus surgery. Yield of colonoscopy
in predicting actual location.
AB - BACKGROUND AND STUDY AIMS: Recent studies suggest that differences in biological
characteristics and risk factors across cancer site within the colon and rectum
may translate to differences in survival. It can be challenging at times to
determine the precise anatomical location of a lesion with a luminal view during
colonoscopy. The aim of this study is to determine if there is a significant
difference between the location of colorectal cancers described by
gastroenterologists in colonoscopies and the actual anatomical location noted on
operative and pathology reports after colon surgery. PATIENTS AND METHODS: A
single-center retrospective analysis of colonoscopies of patient with reported
colonic masses from January 2005 to April 2014 (n = 380) was carried. Assessed
data included demography, operative and pathology reports. Findings were
compared: between the location of colorectal cancers described by
gastroenterologists in colonoscopies and the actual anatomical location noted on
operative reports or pathology samples. RESULTS: We identified 380 colonic
masses, 158 were confirmed adenocarcinomas. Of these 123 underwent surgical
resection, 27 had to be excluded since no specific location was reported on their
operative or pathology report. An absolute difference between endoscopic and
surgical location was found in 32 cases (33 %). Of these, 22 (23 %) differed by 1
colonic segment, 8 (8 %) differed by 2 colonic segments and 2 (2 %) differed by 3
colonic segments. CONCLUSION: There is a significant difference between the
location of colorectal cancers reported by gastroenterologists during endoscopy
and the actual anatomical location noted on operative or pathology reports after
colon surgery. Endoscopic tattooing should be used when faced with any luminal
lesions of interest.
PMID- 28691048
TI - Feasibility of transnasal endoscopy in screening for esophageal and gastric
varices in patients with chronic liver disease.
AB - BACKGROUND AND STUDY AIMS: Screening for esophageal and gastric varices is
indicated for patients with portal hypertension or cirrhosis. Typically,
conventional endoscopy is used; however, the need for sedation increases the
costs and risks, especially in cirrhotic patients. Use of transnasal endoscopy
with an ultrathin endoscope enables study of the upper gastrointestinal tract
without the need for sedation. The objective of this study is to evaluate the
feasibility of transnasal endoscopy in screening for esophageal and gastric
varices in patients with chronic liver disease. PATIENTS AND METHODS : This was a
prospective study in which transnasal endoscopy was carried out in patients with
cirrhosis or portal hypertension who had indications for screening of esophageal
and gastric varices. The following variables were evaluated: demographical data,
duration of procedure, patient tolerance and acceptance, adverse events (AEs),
endoscopic findings and interobserver agreement related to portal hypertension
alterations ( kappa index). RESULTS : A total of 50 patients entered the study.
The most common cause of liver disease was chronic viral hepatitis (66 %). Among
the cirrhotic patients, most of the patients were Child-Pugh A (74 %). In 5
patients (10 %), nasal intubation was not possible. Two patients (4 %)
experienced minor epistaxis. Tolerance was excellent or good in 92 % according
with a visual analogic scale. In 16 patients (32 %), esophageal varices were
detected and in 2 patients (4 %) gastric varices were detected. The mean duration
of the procedure was 7 minutes. CONCLUSIONS : Transnasal endoscopy is feasible,
effective and well tolerated for screening of esophageal and gastric varices in
patients with chronic liver disease. It can be performed in outpatient clinics
safely and without the use of sedation.
PMID- 28691049
TI - Letter to the editor on "Stents and surgical interventions in the palliation of
gastric outlet obstruction: a systematic review".
PMID- 28691050
TI - Evaluation of the bleeding risk with various antithrombotic therapies after
gastric endoscopic submucosal dissection.
AB - BACKGROUND AND STUDY AIMS : Patients receiving antithrombotic drugs have a higher
risk of postoperative bleeding and thromboembolic events related to endoscopic
procedures. The aim of this study was to evaluate the relationship between
various antithrombotic therapies and bleeding after gastric endoscopic submucosal
dissection (ESD) (post-ESD bleeding). PATIENTS AND METHODS: Among 529
consecutive gastric ESD procedures (483 patients with 579 legions), 100 patients
with 121 lesions who underwent 108 procedures were on antithrombotic therapy
(group A) and 382 patients with 458 lesions who underwent 421 procedures were not
on antithrombotic therapy (group B). The ratio of post-ESD bleeding between the
two groups and the bleeding risk related to various antithrombotic therapies were
investigated. RESULTS : Postoperative bleeding was more frequent in group A (11.1
%) than in group B (3.3 %). No thromboembolic events were reported in either
group. Further investigation of antithrombotic therapies in group A demonstrated
that various combinations of antithrombotic agents and heparin replacement were
associated with a higher ratio of post-ESD bleeding. Multivariate analyses
revealed that dual antiplatelet therapy (odds ratio [OR] 10.9, 95 % confidence
interval [CI] 2.1 - 49.5; P = 0.005) and heparin replacement (OR 34.4, 95 %CI
9.4 - 133.2; P < 0.001) were associated with the increased risk of post-ESD
bleeding. In patients on antiplatelet therapy, post-ESD bleeding tended to occur
in the early postoperative period compared with patients on anticoagulant
therapy. CONCLUSIONS: It is necessary to be cautious regarding post-ESD bleeding
in patients requiring antithrombotic therapy, especially patients receiving dual
antiplatelet therapy and heparin replacement. A further prospective study with a
large sample will be needed to confirm these findings.
PMID- 28691051
TI - Peroral endoscopic myotomy using FlushKnife BT: a single-center series.
AB - BACKGROUND AND STUDY AIMS : Peroral endoscopic myotomy (POEM) is an evolving new
treatment strategy for achalasia. Although several kinds of electrosurgical
knives have been used in performing POEM, the best device has yet to be
determined. The FlushKnife BT is a waterjet-emitting short needle-knife with a
small ball tip (BT) that offers the potential to perform all aspects of POEM with
a single device. In this study, we evaluated the safety and efficiency of the
FlushKnife BT for POEM. PATIENTS AND METHODS: A total of 54 consecutive patients
with achalasia and other spastic esophageal motility disorders, such as
jackhammer esophagus or distal esophageal spasm, who underwent POEM between
January 2016 and August 2016, were included in this retrospective study. RESULTS:
The median operation time was 73.0 minutes (range 39 - 184 minutes). All
procedures were completed using only the FlushKnife BT without changing to any
other electrosurgical instrument. The median number of additional submucosal
injections with an injection needle was 0 (range 0 - 1). Endoscopic vessel
sealing was performed a mean of 3 times (range 0 - 7). The median number of
bleeding episodes requiring treatment with hemostatic forceps was 0 (range 0 -
5). There were no significant adverse events. Seven of 52 patients (13.5 %)
reported symptoms of gastroesophageal reflux disease such as heartburn or acid
reflux at 3 month follow-up. CONCLUSIONS: The FlushKnife BT enabled POEM to be
performed with very few device exchanges, either for re-injection or to control
intraoperative bleeding. In this uncontrolled case series, the ability of the
FlushKnife BT to perform nearly all aspects of the POEM procedure seems to make
it particularly well suited to this procedure.
PMID- 28691052
TI - Evaluation of endoscopic submucosal dissection using a new endosurgical knife DN
D2718B: a first clinical feasibility study.
AB - BACKGROUND AND STUDY AIMS : Endosurgical devices with injection function have
been reported to decrease endoscopic submucosal dissection (ESD) operation times
for experts, but the efficacy of these devices for inexperienced endoscopists is
unclear. The aim of this study was to evaluate the feasibility of ESD using a
novel ESD knife (DN-D2718B). PATIENTS AND METHODS : This is a single-center
prospective pilot clinical feasibility study. Patients diagnosed with superficial
gastrointestinal neoplasms were enrolled. A pre-specified group of ESD trainees
with ESD experience on a porcine gastric model and fewer than 30 cases of ESD in
their selected fields performed ESD under expert supervision, using the DN
D2718B. En bloc resection rates, R0 resection rates, procedure times, and
incidence of intra-operational/post-operational adverse events were assessed.
RESULTS : Between June 2015 and January 2016, 13 esophageal, 27 gastric, and 14
colorectal ESD cases were performed per-protocol with mean resection speeds of
10.2, 12.0, and 15.5 mm 2 /min, respectively. There were no intra-operational
complications. CONCLUSION : ESD with this novel knife is feasible even when
performed by non-experts.
PMID- 28691053
TI - Performance report cards increase adenoma detection rate.
AB - BACKGROUND AND STUDY AIMS : Adenoma detection rate (ADR) is an important measure
of colonoscopy quality, as are polyp, advanced ADR, and adenocarcinoma detection
rates. We investigated whether performance report cards improved these outcome
measures. PATIENTS AND METHODS : Endoscopists were given report cards comparing
their detection rates to the institutional mean on an annual basis. Detection
rates were evaluated at baseline, 1 year after report cards (Year 1), and 2 years
after report cards (Year 2). Endoscopists were unaware of the study and received
no other interventions. The primary outcome was ADR and secondary outcomes were
polyp detection rate (PDR), advanced ADR, and adenocarcinoma detection rate.
Multivariate regression was performed to adjust for temporal trends in patient,
endoscopists, and procedural factors. RESULTS: Seventeen physicians performed
3,118 screening colonoscopies in patients with positive FOBT or family history of
colon cancer. The ADR increased from 34.5 % (baseline) to 39.4 % (Year 1) and
41.2 % (Year 2) ( P = 0.0037). The PDR increased from 45 % (baseline) to 48.8 %
(Year 1) and 51.8 % (Year 2) ( P = 0.011). There was no significant improvement
in advanced ADR or adenocarcinoma detection rates. On multivariate analysis, the
ADR increased by 22 % in Year 1 ( P = 0.03) and 30 % in Year 2 ( P = 0.008).
Among physicians with a baseline ADR < 25 %, improvement in ADR was even greater,
increasing 2.2 times by the end of the study ( P = 0.004). Improvements in ADR
were not correlated with specialty although gastroenterologists were 52 % more
likely to find an adenoma than general surgeons. CONCLUSIONS: Annual performance
report cards increased adenoma detection rates, especially among physicians with
low ADR < 25 %.
PMID- 28691054
TI - Use of warm carbon dioxide insufflators does not affect intra-colonic gas
temperature and has no effect on polyp detection rate during colonoscopy - a
randomized controlled trial.
AB - BACKGROUND AND STUDY AIMS : Methods to improve polyp detection during colonoscopy
have been investigated, with conflicting results for warm water irrigation.
Carbon Dioxide (CO 2) warmed to 37 degrees C may have similar or more pronounced
effects on bowel motility. This study aimed to assess whether warmed CO 2 would
improve polyp detection compared to room temperature air insufflation. PATIENTS
AND METHODS: This was a double-blind, randomized controlled trial that enrolled
204 patients undergoing screening or surveillance outpatient colonoscopy. The
primary outcome was polyp per patient detection rate. Secondary outcomes included
adenoma per patient detection rates, bowel spasm, and patient comfort. RESULTS:
The trial was terminated after an interim analysis determined futility. Between
the warmed CO 2 and room air groups, no significant differences were found in the
per-colonoscopy polyp detection rate ( P = 0.57); overall polyp detection rate (
P = 0.69); or adenoma detection rates ( P = 0.74). More patients in the room
temperature group had lower spasm scores (p = 0.02); however, there was a trend
towards greater patient comfort in the warmed CO 2 group ( P = 0.054). An ex
vivo study showed a significant difference between exiting CO 2 temperature at
the insufflator end vs. delivered CO 2 temperature at the colonoscope tip end.
The temperature of insufflation at the tip of the colonoscope was not different
when using warmed vs. unwarmed insufflation ( P = 0.62). CONCLUSION: When
compared with room air insufflation, warmed CO 2 insufflation did not affect
polyp detection rates.
PMID- 28691055
TI - Handling hybrid and missing data in constraint-based causal discovery to study
the etiology of ADHD.
AB - Causal discovery is an increasingly important method for data analysis in the
field of medical research. In this paper, we consider two challenges in causal
discovery that occur very often when working with medical data: a mixture of
discrete and continuous variables and a substantial amount of missing values. To
the best of our knowledge, there are no methods that can handle both challenges
at the same time. In this paper, we develop a new method that can handle these
challenges based on the assumption that data are missing at random and that
continuous variables obey a non-paranormal distribution. We demonstrate the
validity of our approach for causal discovery on simulated data as well as on two
real-world data sets from a monetary incentive delay task and a reversal learning
task. Our results help in the understanding of the etiology of attention
deficit/hyperactivity disorder (ADHD).
PMID- 28691056
TI - Associations between Maternal Hormonal Biomarkers and Maternal Mental and
Physical Health of Very Low Birthweight Infants.
PMID- 28691057
TI - PAM50 gene signatures and breast cancer prognosis with adjuvant anthracycline-
and taxane-based chemotherapy: correlative analysis of C9741 (Alliance).
AB - PAM50 intrinsic breast cancer subtypes are prognostic independent of standard
clinicopathologic factors. CALGB 9741 demonstrated improved recurrence-free (RFS)
and overall survival (OS) with 2-weekly dose-dense (DD) versus 3-weekly therapy.
A significant interaction between intrinsic subtypes and DD-therapy benefit was
hypothesized. Suitable tumor samples were available from 1,471 (73%) of 2,005
subjects. Multiplexed gene-expression profiling generated the PAM50 subtype call,
proliferation score, and risk of recurrence score (ROR-PT) for the evaluable
subset of 1,311 treated patients. The interaction between DD-therapy benefit and
intrinsic subtype was tested in a Cox proportional hazards model using two-sided
alpha = 0.05. Additional multivariable Cox models evaluated the proliferation and
ROR-PT scores as continuous measures with selected clinical covariates. Improved
outcomes for DD therapy in the evaluable subset mirrored results from the
complete data set (RFS; hazard ratio = 1.20; 95% confidence interval = 0.99-1.44)
with 12.3-year median follow-up. Intrinsic subtypes were prognostic of RFS (P <
0.0001) irrespective of treatment assignment. No subtype-specific treatment
effect on RFS was identified (interaction P = 0.44). Proliferation and ROR-PT
scores were prognostic for RFS (both P < 0.0001), but no association with
treatment benefit was seen (P = 0.14 and 0.59, respectively). Results were
similar for OS. The prognostic value of PAM50 intrinsic subtype was greater than
estrogen receptor/HER2 immunohistochemistry classification. PAM50 gene signatures
were highly prognostic but did not predict for improved outcomes with DD
anthracycline- and taxane-based therapy. Clinical validation studies will assess
the ability of PAM50 and other gene signatures to stratify patients and
individualize treatment based on expected risks of distant recurrence.
PMID- 28691058
TI - A Conversation with Stosh Kozimor.
PMID- 28691059
TI - New Ways To Nab Nitrogen.
PMID- 28691060
TI - Tension Promoted Sulfur Exchange for Cellular Delivery.
PMID- 28691061
TI - An Enlightening Reactor.
PMID- 28691062
TI - Framework Chemistry Transforming our Perception of the Solid State.
PMID- 28691063
TI - And for MOFs' Next Trick: Pulling Water out of Thin Air.
PMID- 28691064
TI - Covalent Organic Frameworks as a Platform for Multidimensional Polymerization.
AB - The simultaneous polymerization and crystallization of monomers featuring
directional bonding designs provides covalent organic frameworks (COFs), which
are periodic polymer networks with robust covalent bonds arranged in two- or
three-dimensional topologies. The range of properties characterized in COFs has
rapidly expanded to include those of interest for heterogeneous catalysis, energy
storage and photovoltaic devices, and proton-conducting membranes. Yet many of
these applications will require materials quality, morphological control, and
synthetic efficiency exceeding the capabilities of contemporary synthetic
methods. This level of control will emerge from an improved fundamental
understanding of COF nucleation and growth processes. More powerful
characterization of structure and defects, improved syntheses guided by
mechanistic understanding, and accessing diverse isolated forms, ranging from
single crystals to thin films to colloidal suspensions, remain important frontier
problems.
PMID- 28691065
TI - Porous Molecular Solids and Liquids.
AB - Until recently, porous molecular solids were isolated curiosities with properties
that were eclipsed by porous frameworks, such as metal-organic frameworks. Now
molecules have emerged as a functional materials platform that can have high
levels of porosity, good chemical stability, and, uniquely, solution
processability. The lack of intermolecular bonding in these materials has also
led to new, counterintuitive states of matter, such as porous liquids. Our
ability to design these materials has improved significantly due to advances in
computational prediction methods.
PMID- 28691066
TI - Grand Challenges and Future Opportunities for Metal-Organic Frameworks.
AB - Metal-organic frameworks (MOFs) allow compositional and structural diversity
beyond conventional solid-state materials. Continued interest in the field is
justified by potential applications of exceptional breadth, ranging from gas
storage and separation, which takes advantage of the inherent pores and their
volume, to electronic applications, which requires precise control of electronic
structure. In this Outlook we present some of the pertinent challenges that MOFs
face in their conventional implementations, as well as opportunities in less
traditional areas. Here the aim is to discuss select design concepts and future
research goals that emphasize nuances relevant to this class of materials as a
whole. Particular emphasis is placed on synthetic aspects, as they influence the
potential for MOFs in gas separation, electrical conductivity, and catalytic
applications.
PMID- 28691067
TI - Mimicking Melanosomes: Polydopamine Nanoparticles as Artificial Microparasols.
AB - A primary role of melanin in skin is the prevention of UV-induced nuclear DNA
damage to human skin cells, where it serves to screen out harmful UV radiation.
Melanin is delivered to keratinocytes in the skin after being excreted as
melanosomes from melanocytes. Defects in melanin production in humans can cause
diseases, many of which currently lack effective treatments due to their genetic
origins (e.g., skin cancer, vitiligo, and albinism). The widespread prevalence of
melanin-related diseases and an increasing interest in the performance of various
polymeric materials related to melanin necessitates novel synthetic routes for
preparing melanin-like materials. In this work, we prepared melanin-like
nanoparticles (MelNPs) via spontaneous oxidation of dopamine, as biocompatible,
synthetic analogues of naturally occurring melanosomes, and investigated their
uptake, transport, distribution, and UV-protective capabilities in human
keratinocytes. Critically, we demonstrate that MelNPs are endocytosed, undergo
perinuclear aggregation, and form a supranuclear cap, or so-called microparasol
in human epidermal keratinocytes (HEKa), mimicking the behavior of natural
melananosomes in terms of cellular distribution and the fact that they serve to
protect the cells from UV damage.
PMID- 28691068
TI - Hydrogen-Deuterium Exchange of Lipoxygenase Uncovers a Relationship between
Distal, Solvent Exposed Protein Motions and the Thermal Activation Barrier for
Catalytic Proton-Coupled Electron Tunneling.
AB - Defining specific pathways for efficient heat transfer from protein-solvent
interfaces to their active sites represents one of the compelling and timely
challenges in our quest for a physical description of the origins of enzyme
catalysis. Enzymatic hydrogen tunneling reactions constitute excellent systems in
which to validate experimental approaches to this important question, given the
inherent temperature independence of quantum mechanical wave function overlap.
Herein, we present the application of hydrogen-deuterium exchange coupled to mass
spectrometry toward the spatial resolution of protein motions that can be related
to an enzyme's catalytic parameters. Employing the proton-coupled electron
transfer reaction of soybean lipoxygenase as proof of principle, we first
corroborate the impact of active site mutations on increased local flexibility
and, second, uncover a solvent-exposed loop, 15-34 A from the reactive ferric
center whose temperature-dependent motions are demonstrated to mirror the
enthalpic barrier for catalytic C-H bond cleavage. A network that connects this
surface loop to the active site is structurally identified and supported by
changes in kinetic parameters that result from site-specific mutations.
PMID- 28691069
TI - Synthesis of Single Atom Based Heterogeneous Platinum Catalysts: High Selectivity
and Activity for Hydrosilylation Reactions.
AB - Catalytic hydrosilylation represents a straightforward and atom-efficient
methodology for the creation of C-Si bonds. In general, the application of
homogeneous platinum complexes prevails in industry and academia. Herein, we
describe the first heterogeneous single atom catalysts (SACs), which are
conveniently prepared by decorating alumina nanorods with platinum atoms. The
resulting stable material efficiently catalyzes hydrosilylation of industrially
relevant olefins with high TON (~105). A variety of substrates is selectively
hydrosilylated including compounds with sensitive reducible and other functional
groups (N, B, F, Cl). The single atom based catalyst shows significantly higher
activity compared to related Pt nanoparticles.
PMID- 28691070
TI - Molecular, Local, and Network-Level Basis for the Enhanced Stiffness of Hydrogel
Networks Formed from Coassembled Racemic Peptides: Predictions from Pauling and
Corey.
AB - Hydrogels prepared from self-assembling peptides are promising materials for
medical applications, and using both l- and d-peptide isomers in a gel's
formulation provides an intuitive way to control the proteolytic degradation of
an implanted material. In the course of developing gels for delivery
applications, we discovered that a racemic mixture of the mirror-image beta
hairpin peptides, named MAX1 and DMAX1, provides a fibrillar hydrogel that is
four times more rigid than gels formed by either peptide alone-a puzzling
observation. Herein, we use transmission electron microscopy, small angle neutron
scattering, solid state NMR, diffusing wave, infrared, and fluorescence
spectroscopies, and modeling to determine the molecular basis for the increased
mechanical rigidity of the racemic gel. We find that enantiomeric peptides
coassemble in an alternating fashion along the fibril long axis, forming an
extended heterochiral pleat-like beta-sheet, a structure predicted by Pauling and
Corey in 1953. Hydrogen bonding between enantiomers within the sheet dictates the
placement of hydrophobic valine side chains in the fibrils' dry interior in a
manner that allows the formation of nested hydrophobic interactions between
enantiomers, interactions not accessible within enantiomerically pure fibrils.
Importantly, this unique molecular arrangement of valine side chains maximizes
inter-residue contacts within the core of the fibrils resulting in their local
stiffening, which in turn, gives rise to the significant increase in bulk
mechanical rigidity observed for the racemic hydrogel.
PMID- 28691071
TI - Nanoengineered Ultralight and Robust All-Metal Cathode for High-Capacity, Stable
Lithium-Oxygen Batteries.
AB - The successful development of Li-O2 battery technology depends on resolving the
issue of cathode corrosion by the discharge product (Li2O2) and/or by the
intermediates (LiO2) generated during cell cycling. As an important step toward
this goal, we report for the first time the nanoporous Ni with a nanoengineered
AuNi alloy surface directly attached to Ni foam as a new all-metal cathode
system. Compared with other noncarbonaceous cathodes, the Li-O2 cell with an all
metal cathode is capable of operation with ultrahigh specific capacity (22,551
mAh g-1 at a current density of 1.0 A g-1) and long-term life (286 cycles).
Furthermore, compared with the popularly used carbon cathode, the new all-metal
cathode is advantageous because it does not show measurable reactivity toward
Li2O2 and/or LiO2. As a result, extensive cyclability (40 cycles) with 87.7%
Li2O2 formation and decomposition was obtained. These superior properties are
explained by the enhanced solvation-mediated formation of the discharge products
as well as the tailored properties of the all-metal cathode, including intrinsic
chemical stability, high specific surface area, highly porous structure, high
conductivity, and superior mechanical stability.
PMID- 28691072
TI - Directing the Lithium-Sulfur Reaction Pathway via Sparingly Solvating
Electrolytes for High Energy Density Batteries.
AB - The lithium-sulfur battery has long been seen as a potential next generation
battery chemistry for electric vehicles owing to the high theoretical specific
energy and low cost of sulfur. However, even state-of-the-art lithium-sulfur
batteries suffer from short lifetimes due to the migration of highly soluble
polysulfide intermediates and exhibit less than desired energy density due to the
required excess electrolyte. The use of sparingly solvating electrolytes in
lithium-sulfur batteries is a promising approach to decouple electrolyte quantity
from reaction mechanism, thus creating a pathway toward high energy density that
deviates from the current catholyte approach. Herein, we demonstrate that
sparingly solvating electrolytes based on compact, polar molecules with a 2:1
ratio of a functional group to lithium salt can fundamentally redirect the
lithium-sulfur reaction pathway by inhibiting the traditional mechanism that is
based on fully solvated intermediates. In contrast to the standard catholyte
sulfur electrochemistry, sparingly solvating electrolytes promote intermediate-
and short-chain polysulfide formation during the first third of discharge, before
disproportionation results in crystalline lithium sulfide and a restricted
fraction of soluble polysulfides which are further reduced during the remaining
discharge. Moreover, operation at intermediate temperatures ca. 50 degrees C
allows for minimal overpotentials and high utilization of sulfur at practical
rates. This discovery opens the door to a new wave of scientific inquiry based on
modifying the electrolyte local structure to tune and control the reaction
pathway of many precipitation-dissolution chemistries, lithium-sulfur and beyond.
PMID- 28691073
TI - Group Problem Solving in Class Improves Undergraduate Learning.
AB - Developing methods for improving student learning is a long-standing goal in
undergraduate science education. However, the extent to which students working on
problems in small groups versus individually results in improved learning among
undergraduate science students has not been evaluated in a randomized controlled
trial. We have performed such a trial with 80 students in an undergraduate
biochemistry class, in which students were randomized to either learning in
groups or learning individually. All students participated in the same class,
which consisted of a lecture with periodic breaks for students to solve problems
using an audience response system. Students in the individual learning condition
answered these questions on their own, but students in the group-based learning
condition answered these questions in an assigned group of four students. At the
end of the class, all students then took the same exam as individuals. The exam
had two types of questions-recall questions, in which students had to simply
recall information provided to them, and predict questions, in which students had
to apply their new knowledge to a new context. Students in the individual and
group-based learning conditions performed similarly well on recall questions.
However, students who had been in the group-based learning condition performed
significantly better as individuals on the predict questions. This suggests that
learning in groups may be more effective than individual learning for
undergraduate science students, particularly for applying their knowledge to new
contexts; this highlights the potential need for pedagogical approaches in
undergraduate science courses that incorporate learning in groups.
PMID- 28691074
TI - Redox Catalysis Facilitates Lignin Depolymerization.
AB - Lignin is a recalcitrant and underexploited natural feedstock for aromatic
commodity chemicals, and its degradation generally requires the use of high
temperatures and harsh reaction conditions. Herein we present an ambient
temperature one-pot process for the controlled oxidation and depolymerization of
this potent resource. Harnessing the potential of electrocatalytic oxidation in
conjugation with our photocatalytic cleavage methodology, we have developed an
operationally simple procedure for selective fragmentation of beta-O-4 bonds with
excellent mass recovery, which provides a unique opportunity to expand the
existing lignin usage from energy source to commodity chemicals and synthetic
building block source.
PMID- 28691075
TI - Chimeric Leader Peptides for the Generation of Non-Natural Hybrid RiPP Products.
AB - Combining biosynthetic enzymes from multiple pathways is an attractive approach
for producing molecules with desired structural features; however, progress has
been hampered by the incompatibility of enzymes from unrelated pathways and
intolerance toward alternative substrates. Ribosomally synthesized and
posttranslationally modified peptides (RiPPs) are a diverse natural product class
that employs a biosynthetic logic that is highly amenable to engineering new
compounds. RiPP biosynthetic proteins modify their substrates by binding to a
motif typically located in the N-terminal leader region of the precursor peptide.
Here, we exploit this feature by designing leader peptides that enable
recognition and processing by multiple enzymes from unrelated RiPP pathways.
Using this broadly applicable strategy, a thiazoline-forming cyclodehydratase was
combined with enzymes from the sactipeptide and lanthipeptide families to create
new-to-nature hybrid RiPPs. We also provide insight into design features that
enable control over the hybrid biosynthesis to optimize enzyme compatibility and
establish a general platform for engineering additional hybrid RiPPs.
PMID- 28691076
TI - Self-Assembling Cyclic d,l-alpha-Peptides as Modulators of Plasma HDL Function. A
Supramolecular Approach toward Antiatherosclerotic Agents.
AB - There is great interest in developing new modes of therapy for atherosclerosis to
treat coronary heart disease and stroke, particularly ones that involve
modulation of high-density lipoproteins (HDLs). Here, we describe a new
supramolecular chemotype for altering HDL morphology and function. Guided by
rational design and SAR-driven peptide sequence enumerations, we have synthesized
and determined the HDL remodeling activities of over 80 cyclic d,l-alpha
peptides. We have identified a few distinct sequence motifs that are effective in
vitro in remodeling human and mouse plasma HDLs to increase the concentration of
lipid-poor pre-beta HDLs, which are key initial acceptors of cholesterol in the
reverse cholesterol transport (RCT) process, and concomitantly promote
cholesterol efflux from macrophage cells. Functional assays with various control
peptides, such as scrambled sequences, linear and enantiomeric cyclic peptide
variants, and backbone-modified structures that limit peptide self-assembly,
provide strong support for the supramolecular mode of action. Importantly, when
the lead cyclic peptide c[wLwReQeR] was administered to mice (ip), it also
promoted the formation of small, lipid-poor HDLs in vivo, displayed good plasma
half-life (~6 h), did not appear to have adverse side effects, and exerted potent
anti-inflammatory effects in an acute in vivo inflammation assay. Given that
previously reported HDL remodeling peptides have been based on alpha-helical apoA
I mimetic architectures, the present study, involving a new structural class,
represents a promising step toward new potential therapeutics to combat
atherosclerosis.
PMID- 28691077
TI - A General Small-Scale Reactor To Enable Standardization and Acceleration of
Photocatalytic Reactions.
AB - Photocatalysis for organic synthesis has experienced an exponential growth in the
past 10 years. However, the variety of experimental procedures that have been
reported to perform photon-based catalyst excitation has hampered the
establishment of general protocols to convert visible light into chemical energy.
To address this issue, we have designed an integrated photoreactor for enhanced
photon capture and catalyst excitation. Moreover, the evaluation of this new
reactor in eight photocatalytic transformations that are widely employed in
medicinal chemistry settings has confirmed significant performance advantages of
this optimized design while enabling a standardized protocol.
PMID- 28691078
TI - Novel Strategy for Photopatterning Emissive Polymer Brushes for Organic Light
Emitting Diode Applications.
AB - A light-mediated methodology to grow patterned, emissive polymer brushes with
micron feature resolution is reported and applied to organic light emitting diode
(OLED) displays. Light is used for both initiator functionalization of indium tin
oxide and subsequent atom transfer radical polymerization of methacrylate-based
fluorescent and phosphorescent iridium monomers. The iridium centers play key
roles in photocatalyzing and mediating polymer growth while also emitting light
in the final OLED structure. The scope of the presented procedure enables the
synthesis of a library of polymers with emissive colors spanning the visible
spectrum where the dopant incorporation, position of brush growth, and brush
thickness are readily controlled. The chain-ends of the polymer brushes remain
intact, affording subsequent chain extension and formation of well-defined
diblock architectures. This high level of structure and function control allows
for the facile preparation of random ternary copolymers and red-green-blue arrays
to yield white emission.
PMID- 28691079
TI - Molecular Retrofitting Adapts a Metal-Organic Framework to Extreme Pressure.
AB - Despite numerous studies on chemical and thermal stability of metal-organic
frameworks (MOFs), mechanical stability remains largely undeveloped. To date, no
strategy exists to control the mechanical deformation of MOFs under ultrahigh
pressure. Here, we show that the mechanically unstable MOF-520 can be retrofitted
by precise placement of a rigid 4,4'-biphenyldicarboxylate (BPDC) linker as a
"girder" to afford a mechanically robust framework: MOF-520-BPDC. This
retrofitting alters how the structure deforms under ultrahigh pressure and thus
leads to a drastic enhancement of its mechanical robustness. While in the parent
MOF-520 the pressure transmitting medium molecules diffuse into the pore and
expand the structure from the inside upon compression, the girder in the new
retrofitted MOF-520-BPDC prevents the framework from expansion by linking two
adjacent secondary building units together. As a result, the modified MOF is
stable under hydrostatic compression in a diamond-anvil cell up to 5.5
gigapascal. The increased mechanical stability of MOF-520-BPDC prohibits the
typical amorphization observed for MOFs in this pressure range. Direct
correlation between the orientation of these girders within the framework and its
linear strain was estimated, providing new insights for the design of MOFs with
optimized mechanical properties.
PMID- 28691080
TI - Record Atmospheric Fresh Water Capture and Heat Transfer with a Material
Operating at the Water Uptake Reversibility Limit.
AB - The capture of water vapor at low relative humidity is desirable for producing
potable water in desert regions and for heat transfer and storage. Here, we
report a mesoporous metal-organic framework that captures 82% water by weight
below 30% relative humidity. Under simulated desert conditions, the sorbent would
deliver 0.82 gH2O gMOF-1, nearly double the quantity of fresh water compared to
the previous best material. The material further demonstrates a cooling capacity
of 400 kWh m-3 per cycle, also a record value for a sorbent capable of creating a
20 degrees C difference between ambient and output temperature. The water uptake
in this sorbent is optimized: the pore diameter of our material is above the
critical diameter for water capillary action, enabling water uptake at the limit
of reversibility.
PMID- 28691081
TI - Correction to "Detection of Active Mammalian GH31 alpha-Glucosidases in Health
and Disease Using In-Class, Broad-Spectrum Activity-Based Probes".
AB - [This corrects the article DOI: 10.1021/acscentsci.6b00057.].
PMID- 28691082
TI - Fully gapped superconductivity with no sign change in the prototypical heavy
fermion CeCu2Si2.
AB - In exotic superconductors, including high-Tc copper oxides, the interactions
mediating electron Cooper pairing are widely considered to have a magnetic rather
than a conventional electron-phonon origin. Interest in this exotic pairing was
initiated by the 1979 discovery of heavy-fermion superconductivity in CeCu2Si2,
which exhibits strong antiferromagnetic fluctuations. A hallmark of
unconventional pairing by anisotropic repulsive interactions is that the
superconducting energy gap changes sign as a function of the electron momentum,
often leading to nodes where the gap goes to zero. We report low-temperature
specific heat, thermal conductivity, and magnetic penetration depth measurements
in CeCu2Si2, demonstrating the absence of gap nodes at any point on the Fermi
surface. Moreover, electron irradiation experiments reveal that the
superconductivity survives even when the electron mean free path becomes
substantially shorter than the superconducting coherence length. This indicates
that superconductivity is robust against impurities, implying that there is no
sign change in the gap function. These results show that, contrary to long
standing belief, heavy electrons with extremely strong Coulomb repulsions can
condense into a fully gapped s-wave superconducting state, which has an on-site
attractive pairing interaction.
PMID- 28691083
TI - Sub-100-nm metafluorophores with digitally tunable optical properties self
assembled from DNA.
AB - Fluorescence microscopy allows specific target detection down to the level of
single molecules and has become an enabling tool in biological research. To
transduce the biological information to an imageable signal, we have developed a
variety of fluorescent probes, such as organic dyes or fluorescent proteins with
different colors. Despite their success, a limitation on constructing small
fluorescent probes is the lack of a general framework to achieve precise and
programmable control of critical optical properties, such as color and
brightness. To address this challenge, we introduce metafluorophores, which are
constructed as DNA nanostructure-based fluorescent probes with digitally tunable
optical properties. Each metafluorophore is composed of multiple organic
fluorophores, organized in a spatially controlled fashion in a compact sub-100-nm
architecture using a DNA nanostructure scaffold. Using DNA origami with a size of
90 * 60 nm2, substantially smaller than the optical diffraction limit, we
constructed small fluorescent probes with digitally tunable brightness, color,
and photostability and demonstrated a palette of 124 virtual colors. Using these
probes as fluorescent barcodes, we implemented an assay for multiplexed
quantification of nucleic acids. Additionally, we demonstrated the triggered in
situ self-assembly of fluorescent DNA nanostructures with prescribed brightness
upon initial hybridization to a nucleic acid target.
PMID- 28691084
TI - Cost-effective conservation of amphibian ecology and evolution.
AB - Habitat loss is the most important threat to species survival, and the efficient
selection of priority areas is fundamental for good systematic conservation
planning. Using amphibians as a conservation target, we designed an innovative
assessment strategy, showing that prioritization models focused on functional,
phylogenetic, and taxonomic diversity can include cost-effectiveness-based
assessments of land values. We report new key conservation sites within the
Brazilian Atlantic Forest hot spot, revealing a congruence of ecological and
evolutionary patterns. We suggest payment for ecosystem services through
environmental set-asides on private land, establishing potential trade-offs for
ecological and evolutionary processes. Our findings introduce additional
effective area-based conservation parameters that set new priorities for
biodiversity assessment in the Atlantic Forest, validating the usefulness of a
novel approach to cost-effectiveness-based assessments of conservation value for
other species-rich regions.
PMID- 28691085
TI - Microsecond photocapacitance transients observed using a charged microcantilever
as a gated mechanical integrator.
AB - How light is converted to electricity in blends of organic donor and acceptor
molecules is an unsettled question, partly because the spatial heterogeneity
present in these blends makes them challenging to characterize. Although scanned
probe measurements have provided crucially important microscopic insights into
charge generation and transport in these blends, achieving the subnanosecond time
resolution needed to directly observe the fate of photogenerated charges has
proven difficult. We use a charged microcantilever as a gated mechanical
integrator to record photocapacitance indirectly by measuring the accumulated
change in cantilever phase as a function of the time delay between precisely
synchronized voltage and light pulses. In contrast with previous time-resolved
scanned-probe photocapacitance measurements, the time resolution of this method
is set by the rise and fall time of the voltage and light pulses and not by the
inverse detection bandwidth. We demonstrate in an organic donor-acceptor blend
the ability of this indirect, "phase-kick" technique to record multiexponential
photocapacitance transients on time scales ranging from 40 MUs to 10 ms. The
technique's ability to measure subcycle, nanosecond charge dynamics is
demonstrated by measuring the tens of nanosecond sample electrical charging time.
PMID- 28691086
TI - Serotonin rebalances cortical tuning and behavior linked to autism symptoms in
15q11-13 CNV mice.
AB - Serotonin is a critical modulator of cortical function, and its metabolism is
defective in autism spectrum disorder (ASD) brain. How serotonin metabolism
regulates cortical physiology and contributes to the pathological and behavioral
symptoms of ASD remains unknown. We show that normal serotonin levels are
essential for the maintenance of neocortical excitation/inhibition balance,
correct sensory stimulus tuning, and social behavior. Conversely, low serotonin
levels in 15q dup mice (a model for ASD with the human 15q11-13 duplication)
result in impairment of the same phenotypes. Restoration of normal serotonin
levels in 15q dup mice revealed the reversibility of a subset of ASD-related
symptoms in the adult. These findings suggest that serotonin may have therapeutic
potential for discrete ASD symptoms.
PMID- 28691087
TI - Cytoskeletal actin dynamics shape a ramifying actin network underpinning
immunological synapse formation.
AB - T cell activation and especially trafficking of T cell receptor microclusters
during immunological synapse formation are widely thought to rely on cytoskeletal
remodeling. However, important details on the involvement of actin in the latter
transport processes are missing. Using a suite of advanced optical microscopes to
analyze resting and activated T cells, we show that, following contact formation
with activating surfaces, these cells sequentially rearrange their cortical actin
across the entire cell, creating a previously unreported ramifying actin network
above the immunological synapse. This network shows all the characteristics of an
inward-growing transportation network and its dynamics correlating with T cell
receptor rearrangements. This actin reorganization is accompanied by an increase
in the nanoscale actin meshwork size and the dynamic adjustment of the turnover
times and filament lengths of two differently sized filamentous actin
populations, wherein formin-mediated long actin filaments support a very flat and
stiff contact at the immunological synapse interface. The initiation of
immunological synapse formation, as highlighted by calcium release, requires
markedly little contact with activating surfaces and no cytoskeletal
rearrangements. Our work suggests that incipient signaling in T cells initiates
global cytoskeletal rearrangements across the whole cell, including a stiffening
process for possibly mechanically supporting contact formation at the
immunological synapse interface as well as a central ramified transportation
network apparently directed at the consolidation of the contact and the delivery
of effector functions.
PMID- 28691088
TI - The effects of external cues on individual and collective behavior of shoaling
fish.
AB - Collective animal behavior is an emergent phenomenon arising from the local
interactions of the members of animal groups. Considerable progress has been made
in characterizing these interactions, particularly inferring rules that shape and
guide the responses of animals to their near neighbors. To date, experimental
work has focused on collective behavior within a single, stable context. We
examine the individual and collective behavior of a schooling fish species, the x
ray tetra (Pristella maxillaris), identifying their response to changes in
context produced by food cues or conspecific alarm cues. Fish exposed to alarm
cues show pronounced, broad-ranging changes of behavior, including reducing speed
and predictability in their movements. Alarmed fish also alter their responses to
other group members, including enacting a smaller zone of repulsion and
increasing their frequency of observation of, and responsiveness to, near
neighbors. Fish subject to food cues increased speed as a function of neighbor
positions and reduced encounter frequency with near neighbors. Overall, changes
in individual behavior and the interactions among individuals in response to
external cues coincide with changes in group-level patterns, providing insight
into the adaptability of behavior to changes in context and interrelationship
between local interactions and global patterns in collective behavior.
PMID- 28691089
TI - A general strategy to synthesize chemically and topologically anisotropic Janus
particles.
AB - Emulsion polymerization is the most widely used synthetic technique for
fabricating polymeric particles. The interfacial tension generated with this
technique limits the ability to tune the topology and chemistry of the resultant
particles. We demonstrate a general emulsion interfacial polymerization approach
that involves introduction of additional anchoring molecules surrounding the
microdroplets to synthesize a large variety of Janus particles with controllable
topological and chemical anisotropy. This strategy is based on interfacial
polymerization mediated by an anchoring effect at the interface of microdroplets.
Along the interface of the microdroplets, the diverse topology and surface
chemistry features of the Janus particles can be precisely tuned by regulating
the monomer type and concentration as well as polymerization time. This method is
applicable to a wide variety of monomers, including positively charged, neutrally
charged, and negatively charged monomers, thereby enriching the community of
Janus particles.
PMID- 28691090
TI - Two orders of magnitude enhancement in oxygen evolution reactivity on amorphous
Ba0.5Sr0.5Co0.8Fe0.2O3-delta nanofilms with tunable oxidation state.
AB - Perovskite oxides exhibit potential for use as electrocatalysts in the oxygen
evolution reaction (OER). However, their low specific surface area is the main
obstacle to realizing a high mass-specific activity that is required to be
competitive against the state-of-the-art precious metal-based catalysts. We
report the enhanced performance of Ba0.5Sr0.5Co0.8Fe0.2O3-delta (BSCF) for the
OER with intrinsic activity that is significantly higher than that of the
benchmark IrO2, and this result was achieved via fabrication of an amorphous BSCF
nanofilm on a surface-oxidized nickel substrate by magnetron sputtering. The
surface nickel oxide layer of the Ni substrate and the thickness of the BSCF film
were further used to tune the intrinsic OER activity and stability of the BSCF
catalyst by optimizing the electronic configuration of the transition metal
cations in BSCF via the interaction between the nanofilm and the surface nickel
oxide, which enables up to 315-fold enhanced mass-specific activity compared to
the crystalline BSCF bulk phase. Moreover, the amorphous BSCF-Ni foam anode
coupled with the Pt-Ni foam cathode demonstrated an attractive small
overpotential of 0.34 V at 10 mA cm-2 for water electrolysis, with a BSCF loading
as low as 154.8 MUg cm-2.
PMID- 28691091
TI - Electronic structure of aqueous solutions: Bridging the gap between theory and
experiments.
AB - Predicting the electronic properties of aqueous liquids has been a long-standing
challenge for quantum mechanical methods. However, it is a crucial step in
understanding and predicting the key role played by aqueous solutions and
electrolytes in a wide variety of emerging energy and environmental technologies,
including battery and photoelectrochemical cell design. We propose an efficient
and accurate approach to predict the electronic properties of aqueous solutions,
on the basis of the combination of first-principles methods and experimental
validation using state-of-the-art spectroscopic measurements. We present results
of the photoelectron spectra of a broad range of solvated ions, showing that
first-principles molecular dynamics simulations and electronic structure
calculations using dielectric hybrid functionals provide a quantitative
description of the electronic properties of the solvent and solutes, including
excitation energies. The proposed computational framework is general and
applicable to other liquids, thereby offering great promise in understanding and
engineering solutions and liquid electrolytes for a variety of important energy
technologies.
PMID- 28691092
TI - Instant tough bonding of hydrogels for soft machines and electronics.
AB - Introducing methods for instant tough bonding between hydrogels and antagonistic
materials-from soft to hard-allows us to demonstrate elastic yet tough biomimetic
devices and machines with a high level of complexity. Tough hydrogels strongly
attach, within seconds, to plastics, elastomers, leather, bone, and metals,
reaching unprecedented interfacial toughness exceeding 2000 J/m2. Healing of
severed ionic hydrogel conductors becomes feasible and restores function
instantly. Soft, transparent multilayered hybrids of elastomers and ionic
hydrogels endure biaxial strain with more than 2000% increase in area,
facilitating soft transducers, generators, and adaptive lenses. We demonstrate
soft electronic devices, from stretchable batteries, self-powered compliant
circuits, and autonomous electronic skin for triggered drug delivery. Our
approach is applicable in rapid prototyping and in delicate environments
inaccessible for extended curing and cross-linking.
PMID- 28691093
TI - WNT antagonists exhibit unique combinatorial antitumor activity with taxanes by
potentiating mitotic cell death.
AB - The WNT pathway mediates intercellular signaling that regulates cell fate in both
normal development and cancer. It is widely appreciated that the WNT pathway is
frequently dysregulated in human cancers through a variety of genetic and
epigenetic mechanisms. Targets in the WNT pathway are being extensively pursued
for the development of new anticancer therapies, and we have advanced two WNT
antagonists for clinical development: vantictumab (anti-FZD) and ipafricept (FZD8
Fc). We examined the antitumor efficacy of these WNT antagonists in combination
with various chemotherapies in a large set of patient-derived xenograft models.
In responsive models, WNT blockade led to profound synergy with taxanes such as
paclitaxel, and the combination activity with taxanes was consistently more
effective than with other classes of chemotherapy. Taxane monotherapy increased
the frequency of cells with active WNT signaling. This selection of WNT-active
chemotherapy-resistant tumorigenic cells was prevented by WNT-antagonizing
biologics and required sequential dosing of the WNT antagonist followed by the
taxane. The WNT antagonists potentiated paclitaxel-mediated mitotic blockade and
promoted widespread mitotic cell death. By blocking WNT/beta-catenin signaling
before mitotic blockade by paclitaxel, we found that this treatment effectively
sensitizes cancer stem cells to taxanes. This combination strategy and treatment
regimen has been incorporated into ongoing clinical testing for vantictumab and
ipafricept.
PMID- 28691094
TI - Probing nanocrystalline grain dynamics in nanodevices.
AB - Dynamical structural defects exist naturally in a wide variety of solids. They
fluctuate temporally and hence can deteriorate the performance of many electronic
devices. Thus far, the entities of these dynamic objects have been identified to
be individual atoms. On the other hand, it is a long-standing question whether a
nanocrystalline grain constituted of a large number of atoms can switch, as a
whole, reversibly like a dynamical atomic defect (that is, a two-level system).
This is an emergent issue considering the current development of nanodevices with
ultralow electrical noise, qubits with long quantum coherence time, and
nanoelectromechanical system sensors with ultrahigh resolution. We demonstrate
experimental observations of dynamic nanocrystalline grains that repeatedly
switch between two or more metastable coordinate states. We study temporal
resistance fluctuations in thin ruthenium dioxide (RuO2) metal nanowires and
extract microscopic parameters, including relaxation time scales, mobile grain
sizes, and the bonding strengths of nanograin boundaries. These material
parameters are not obtainable by other experimental approaches. When combined
with previous in situ high-resolution transmission electron microscopy, our
electrical method can be used to infer rich information about the structural
dynamics of a wide variety of nanodevices and new two-dimensional materials.
PMID- 28691095
TI - Condensin II is anchored by TFIIIC and H3K4me3 in the mammalian genome and
supports the expression of active dense gene clusters.
AB - Structural maintenance of chromosome complexes, such as cohesin, have been
implicated in a wide variety of chromatin-dependent functions such as genome
organization, replication, and gene expression. How these complexes find their
sites of association and affect local chromosomal processes is not well
understood. We report that condensin II, a complex distinct from cohesin,
physically interacts with TFIIIC, and they both colocalize at active gene
promoters in the mouse and human genomes, facilitated by interaction between
NCAPD3 and the epigenetic mark H3K4me3. Condensin II is important for maintaining
high levels of expression of the histone gene clusters as well as the interaction
between these clusters in the mouse genome. Our findings suggest that condensin
II is anchored to the mammalian genome by a combination of H3K4me3 and the
sequence-specific binding of TFIIIC, and that condensin supports the expression
of active gene-dense regions found at the boundaries of topological domains.
Together, our results support a working model in which condensin II contributes
to topological domain boundary-associated gene activity in the mammalian genome.
PMID- 28691096
TI - Nanoscale simultaneous chemical and mechanical imaging via peak force infrared
microscopy.
AB - Nondestructive chemical and mechanical measurements of materials with ~10-nm
spatial resolution together with topography provide rich information on the
compositions and organizations of heterogeneous materials and nanoscale objects.
However, multimodal nanoscale correlations are difficult to achieve because of
the limitation on spatial resolution of optical microscopy and constraints from
instrumental complexities. We report a novel noninvasive spectroscopic scanning
probe microscopy method-peak force infrared (PFIR) microscopy-that allows
chemical imaging, collection of broadband infrared spectra, and mechanical
mapping at a spatial resolution of 10 nm. In our technique, chemical absorption
information is directly encoded in the withdraw curve of the peak force tapping
cycle after illumination with synchronized infrared laser pulses in a simple
apparatus. Nanoscale phase separation in block copolymers and inhomogeneity in
CH3NH3PbBr3 perovskite crystals are studied with correlative infrared/mechanical
nanoimaging. Furthermore, we show that the PFIR method is sensitive to the
presence of surface phonon polaritons in boron nitride nanotubes. PFIR microscopy
will provide a powerful analytical tool for explorations at the nanoscale across
wide disciplines.
PMID- 28691097
TI - Above 400-K robust perpendicular ferromagnetic phase in a topological insulator.
AB - The quantum anomalous Hall effect (QAHE) that emerges under broken time-reversal
symmetry in topological insulators (TIs) exhibits many fascinating physical
properties for potential applications in nanoelectronics and spintronics.
However, in transition metal-doped TIs, the only experimentally demonstrated QAHE
system to date, the QAHE is lost at practically relevant temperatures. This
constraint is imposed by the relatively low Curie temperature (Tc) and inherent
spin disorder associated with the random magnetic dopants. We demonstrate
drastically enhanced Tc by exchange coupling TIs to Tm3Fe5O12, a high-Tc magnetic
insulator with perpendicular magnetic anisotropy. Signatures showing that the TI
surface states acquire robust ferromagnetism are revealed by distinct squared
anomalous Hall hysteresis loops at 400 K. Point-contact Andreev reflection
spectroscopy confirms that the TI surface is spin-polarized. The greatly enhanced
Tc, absence of spin disorder, and perpendicular anisotropy are all essential to
the occurrence of the QAHE at high temperatures.
PMID- 28691098
TI - High particulate iron(II) content in glacially sourced dusts enhances
productivity of a model diatom.
AB - Little is known about the bioavailability of iron (Fe) in natural dusts and the
impact of dust mineralogy on Fe utilization by photosynthetic organisms.
Variation in the supply of bioavailable Fe to the ocean has the potential to
influence the global carbon cycle by modulating primary production in the
Southern Ocean. Much of the dust deposited across the Southern Ocean is sourced
from South America, particularly Patagonia, where the waxing and waning of past
and present glaciers generate fresh glaciogenic material that contrasts with aged
and chemically weathered nonglaciogenic sediments. We show that these two
potential sources of modern-day dust are mineralogically distinct, where
glaciogenic dust sources contain mostly Fe(II)-rich primary silicate minerals,
and nearby nonglaciogenic dust sources contain mostly Fe(III)-rich oxyhydroxide
and Fe(III) silicate weathering products. In laboratory culture experiments,
Phaeodactylum tricornutum, a well-studied coastal model diatom, grows more
rapidly, and with higher photosynthetic efficiency, with input of glaciogenic
particulates compared to that of nonglaciogenic particulates due to these
differences in Fe mineralogy. Monod nutrient accessibility models fit to our data
suggest that particulate Fe(II) content, rather than abiotic solubility, controls
the Fe bioavailability in our Fe fertilization experiments. Thus, it is possible
for this diatom to access particulate Fe in dusts by another mechanism besides
uptake of unchelated Fe (Fe') dissolved from particles into the bulk solution. If
this capability is widespread in the Southern Ocean, then dusts deposited to the
Southern Ocean in cold glacial periods are likely more bioavailable than those
deposited in warm interglacial periods.
PMID- 28691099
TI - Selective targeting of primary and secondary nucleation pathways in Abeta42
aggregation using a rational antibody scanning method.
AB - Antibodies targeting Abeta42 are under intense scrutiny because of their
therapeutic potential for Alzheimer's disease. To enable systematic searches, we
present an "antibody scanning" strategy for the generation of a panel of
antibodies against Abeta42. Each antibody in the panel is rationally designed to
target a specific linear epitope, with the selected epitopes scanning the Abeta42
sequence. By screening in vitro the panel to identify the specific microscopic
steps in the Abeta42 aggregation process influenced by each antibody, we identify
two antibodies that target specifically the primary and the secondary nucleation
steps, which are key for the production of Abeta42 oligomers. These two
antibodies act, respectively, to delay the onset of aggregation and to block the
proliferation of aggregates, and correspondingly reduce the toxicity in a
Caenorhabditis elegans model overexpressing Abeta42. These results illustrate how
the antibody scanning method described here can be used to readily obtain very
small antibody libraries with extensive coverage of the sequences of target
proteins.
PMID- 28691100
TI - Nonvolatile ferroelectric domain wall memory.
AB - Ferroelectric domain walls are atomically sharp topological defects that separate
regions of uniform polarization. The discovery of electrical conductivity in
specific types of walls gave rise to "domain wall nanoelectronics," a technology
in which the wall (rather than the domain) stores information. This paradigm
shift critically hinges on precise nanoengineering of reconfigurable domain
walls. Using specially designed nanofabricated electrodes and scanning probe
techniques, we demonstrate a prototype nonvolatile ferroelectric domain wall
memory, scalable to below 100 nm, whose binary state is defined by the existence
or absence of conductive walls. The device can be read out nondestructively at
moderate voltages (<3 V), exhibits relatively high OFF-ON ratios (~103) with
excellent endurance and retention characteristics, and has multilevel data
storage capacity. Our work thus constitutes an important step toward integrated
nanoscale ferroelectric domain wall memory devices.
PMID- 28691101
TI - Advancing Discontinuous Fiber-Reinforced Composites above Critical Length for
Replacing Current Dental Composites and Amalgam.
AB - Clinicians have been aware that posterior dental particulate-filled composites
(PFCs) have many placement disadvantages and indeed fail clinically at an average
rate faster than amalgam alloys. Secondary caries is most commonly identified as
the chief failure mechanism for both dental PFCs and amalgam. In terms of a
solution, fiber-reinforced composites (FRCs) above critical length (Lc) can
provide mechanical property safety factors with compound molding packing
qualities to reduce many problems associated with dental PFCs. Discontinuous
chopped fibers above the necessary Lc have been incorporated into dental PFCs to
make consolidated molding compounds that can be tested for comparisons with PFC
controls on mechanical properties, wear resistance, void-defect occurrence and
packing ability to reestablish the interproximal contact. Further, imaging
characterizations can aid in providing comparisons for FRCs with other materials
using scanning electron microscopy, atomic force microscopy and photographs.
Also, the amalgam filling material has finally been tested by appropriate ASTM
flexural bending methods that eliminate shear failure associated with short span
lengths in dental standards for comparison with dental PFCs to best explain
increased longevity for the amalgam when compared to dental PFCs. Accurate
mechanical tests also provide significant proof for superior advantages with
FRCs. Mechanical properties tested included flexural strength, yield strength,
modulus, resilience, work of fracture, critical strain energy release and
critical stress intensity factor. FRC molding compounds with fibers above Lc
extensively improve all mechanical properties over PFC dental paste and over the
amalgam for all mechanical properties except modulus. The dental PFC also
demonstrated superior mechanical properties over the amalgam except modulus to
provide a better explanation for increased PFC failure due to secondary caries.
With lower PFC modulus, increased adhesive bond breakage is expected from greater
interlaminar shearing as the PFC accentuates straining deflections compared to
amalgam at the higher modulus tooth enamel margins during loading. Preliminary
testing for experimental FRCs with fibers above Lc demonstrated three-body wear
even less than enamel to reduce the possibility of marginal ditching as a factor
in secondary caries seen with both PFCs and amalgam. Further, FRC molding
compounds with chopped fibers above Lc properly impregnated with photocure resin
can pack with condensing forces higher than the amalgam to eliminate voids in the
proximal box commonly seen with dental PFCs and reestablish interproximal
contacts better than amalgam. Subsequent higher FRC packing forces can aid in
squeezing monomer, resin, particulate and nanofibers deeper into adhesive
mechanical bond retention sites and then leave a higher concentration of
insoluble fibers and particulate as moisture barriers at the cavity margins.
Also, FRC molding compounds can incorporate triclosan antimicrobial and maintain
a strong packing condensing force that cannot be accomplished with PFCs which
form a sticky gluey consistency with triclosan. In addition, large FRC packing
forces allow higher concentrations of the hydrophobic ethoxylated bis phenol A
dimethacrylate (BisEMA) low-viscosity oligomer resin that reduces water sorption
and solubility to then still maintain excellent consistency. Therefore, photocure
molding compounds with fibers above Lc appear to have many exceptional properties
and design capabilities as improved alternatives for replacing both PFCs and
amalgam alloys in restorative dental care.
PMID- 28691102
TI - DCE-MRI Texture Features for Early Prediction of Breast Cancer Therapy Response.
AB - This study investigates the effectiveness of hundreds of texture features
extracted from voxel-based dynamic contrast-enhanced magnetic resonance imaging
(DCE-MRI) parametric maps for early prediction of breast cancer response to
neoadjuvant chemotherapy (NAC). In total, 38 patients with breast cancer
underwent DCE-MRI before (baseline) and after the first of the 6-8 NAC cycles.
Quantitative pharmacokinetic (PK) parameters and semiquantitative metrics were
estimated from DCE-MRI time-course data. The residual cancer burden (RCB) index
value was computed based on pathological analysis of surgical specimens after NAC
completion. In total, 1043 texture features were extracted from each of the 13
parametric maps of quantitative PK or semiquantitative metric, and their
capabilities for early prediction of RCB were examined by correlating feature
changes between the 2 MRI studies with RCB. There were 1069 pairs of feature-map
combinations that showed effectiveness for response prediction with 4 correlation
coefficients >0.7. The 3-dimensional gray-level cooccurrence matrix was the most
effective feature extraction method for therapy response prediction, and, in
general, the statistical features describing texture heterogeneity were the most
effective features. Quantitative PK parameters, particularly those estimated with
the shutter-speed model, were more likely to generate effective features for
prediction response compared with the semiquantitative metrics. The best feature
map pair could predict pathologic complete response with 100% sensitivity and
100% specificity using our cohort. In conclusion, breast tumor heterogeneity in
microvasculature as measured by texture features of voxel-based DCE-MRI
parametric maps could be a useful biomarker for early prediction of NAC response.
PMID- 28691103
TI - Role of nonalcoholic fatty liver disease as risk factor for drug-induced
hepatotoxicity.
AB - BACKGROUND: Obesity is often associated with nonalcoholic fatty liver disease
(NAFLD), which refers to a large spectrum of hepatic lesions including fatty
liver, nonalcoholic steatohepatitis (NASH) and cirrhosis. Different
investigations showed or suggested that obesity and NAFLD are able to increase
the risk of hepatotoxicity of different drugs. Some of these drugs could induce
more frequently an acute hepatitis in obese individuals whereas others could
worsen pre-existing NAFLD. AIM: The main objective of the present review was to
collect the available information regarding the role of NAFLD as risk factor for
drug-induced hepatotoxicity. For this purpose, we performed a data-mining
analysis using different queries including drug-induced liver injury (or DILI),
drug-induced hepatotoxicity, fatty liver, nonalcoholic fatty liver disease (or
NAFLD), steatosis and obesity. The main data from the collected articles are
reported in this review and when available, some pathophysiological hypotheses
are put forward. RELEVANCE FOR PATIENTS: Drugs that could pose a potential risk
in obese patients include compounds belonging to different pharmacological
classes such as acetaminophen, halothane, methotrexate, rosiglitazone, stavudine
and tamoxifen. For some of these drugs, experimental investigations in obese
rodents confirmed the clinical observations and unveiled different
pathophysiological mechanisms which could explain why these pharmaceuticals are
particularly hepatotoxic in obesity and NAFLD. Other drugs such as
pentoxifylline, phenobarbital and omeprazole might also pose a risk but more
investigations are required to determine whether this risk is significant or not.
Because obese people often take several drugs for the treatment of different
obesity-related diseases such as type 2 diabetes, hyperlipidemia and coronary
heart disease, it is urgent to identify the main pharmaceuticals that can cause
acute hepatitis on a fatty liver background or induce NAFLD worsening.
PMID- 28691105
TI - Bottom-up Gamma: the Pedunculopontine Nucleus and Reticular Activating System.
AB - Gamma rhythms have been proposed to promote the feed forward or "bottom-up" flow
of information from lower to higher regions in the brain during perception. On
the other hand, beta rhythms have been proposed to represent feed back or "top
down" influence from higher regions to lower. The pedunculopontine nucleus (PPN)
has been implicated in sleep-wake control and arousal, and is part of the
reticular activating system (RAS). This review describes the properties of the
cells in this nucleus. These properties are unique, and perhaps it is the
particular characteristics of these cells that allow the PPN to be involved in a
host of functions and disorders. The fact that all PPN neurons fire maximally at
gamma band frequency regardless of electrophysiological or transmitter type, make
this an unusual cell group. In other regions, for example in the cortex, cells
with such a property represent only a sub-population. More importantly, the fact
that this cell group's functions are related to the capacity to generate coherent
activity at a preferred natural frequency, gamma band, speaks volumes about how
the PPN functions. We propose that "bottom-up" gamma band influence arises in the
RAS and contributes to the build-up of the background of activity necessary for
preconscious awareness and gamma activity at cortical levels.
PMID- 28691104
TI - Genetic and epigenetic modifications in the pathogenesis of diabetic retinopathy:
a molecular link to regulate gene expression.
AB - Intensification in the frequency of diabetes and the associated vascular
complications has been a root cause of blindness and visual impairment worldwide.
One such vascular complication which has been the prominent cause of blindness;
retinal vasculature, neuronal and glial abnormalities is diabetic retinopathy
(DR), a chronic complicated outcome of Type 1 and Type 2 diabetes. It has also
become clear that "genetic" variations in population alone can't explain the
development and progression of diabetes and its complications including DR. DR
experiences engagement of foremost mediators of diabetes such as hyperglycemia,
oxidant stress, and inflammatory factors that lead to the dysregulation of
"epigenetic" mechanisms involving histone acetylation and histone and DNA
methylation, chromatin remodeling and expression of a complex set of stress
regulated and disease-associated genes. In addition, both elevated glucose
concentration and insulin resistance leave a robust effect on epigenetic
reprogramming of the endothelial cells too, since endothelium associated with the
eye aids in maintaining the vascular homeostasis. Furthermore, several studies
conducted on the disease suggest that the modifications of the epigenome might be
the fundamental mechanism(s) for the proposed metabolic memory' resulting into
prolonged gene expression for inflammation and cellular dysfunction even after
attaining the glycemic control in diabetics. Henceforth, the present review
focuses on the aspects of genetic and epigenetic alterations in genes such as
vascular endothelial growth factor and aldose reductase considered being
associated with DR. In addition, we discuss briefly the role of the thioredoxin
interacting protein TXNIP, which is strongly induced by high glucose and
diabetes, in cellular oxidative stress and mitochondrial dysfunction potentially
leading to chromatin remodeling and ocular complications of diabetes. The
identification of disease-associated genes and their epigenetic regulations will
lead to potential new drugs and gene therapies as well as personalized medicine
to prevent or slow down the progression of DR.
PMID- 28691106
TI - Recombinant myostatin reduces highly expressed microRNAs in differentiating C2C12
cells.
AB - Myostatin is small glycopeptide that is produced and secreted by skeletal muscle.
It is a potent negative regulator of muscle growth that has been associated with
conditions of frailty. In C2C12 cells, myostatin limits cell differentiation.
Myostatin acts through activin receptor IIB, activin receptor-like kinase (ALK)
and Smad transcription factors. microRNAs (miRNA) are short, 22 base pair
nucleotides that bind to the 3' UTR of target mRNA to repress translation or
reduce mRNA stability. In the present study, expression in differentiating C2C12
cells of the myomiRs miR-1 and 133a were down-regulated following treatment with
1 MUg of recombinant myostatin at 1 d post-induction of differentiation while all
myomiRs (miR-1, 133a/b and 206) were upregulated by SB431542, a potent ALK4/5/7
inhibitor which reduces Smad2 signaling, at 1 d and all, with the exception of
miR-206, were upregulated by SB431542 at 3 d. The expression of the muscle
enriched miR-486 was greater following treatment with SB431542 but not altered by
myostatin. Other highly expressed miRNAs in skeletal muscle, miR-23a/b and 145,
were altered only at 1 d post-induction of differentiation. miR-27b responded
differently to treatments at 1 d, where it was upregulated, as compared to 3 d,
where it was downregulated. Neither myostatin nor SB431542 altered cell size or
cell morphology. The data indicate that myostatin represses myomiR expression in
differentiating C2C12 cells and that inhibition of Smad signaling with SB431542
can result in large changes in highly expressed miRNAs in differentiating
myoblasts.
PMID- 28691107
TI - Network-based approaches that exploit inferred transcription factor activity to
analyze the impact of genetic variation on gene expression.
AB - Over the past decade, a number of methods have emerged for inferring protein
level transcription factor activities in individual samples based on prior
information about the structure of the gene regulatory network. We discuss how
this has enabled new methods for dissecting trans-acting mechanisms that underpin
genetic variation in gene expression.
PMID- 28691108
TI - Jetting of a shear banding fluid in rectangular ducts.
AB - Non-Newtonian fluids are susceptible to flow instabilities such as shear banding,
in which the fluid may exhibit a markedly discontinuous viscosity at a critical
stress. Here we report the characteristics and causes of a jetting flow
instability of shear banding wormlike micelle solutions in microfluidic channels
with rectangular cross sections over an intermediate volumetric flow regime.
Particle-tracking methods are used to measure the three-dimensional flow field in
channels of differing aspect ratios, sizes, and wall materials. When jetting
occurs, it is self-contained within a portion of the channel where the flow
velocity is greater than the surroundings. We observe that the instability forms
in channels with aspect ratio greater than 5, and that the location of the high
velocity jet appears to be sensitive to stress localizations. Jetting is not
observed in a lower concentration solution without shear banding. Simulations
using the Johnson-Segalman viscoelastic model show a qualitatively similar
behavior to the experimental observations and indicate that compressive normal
stresses in the cross-stream directions support the development of the jetting
flow. Our results show that nonuniform flow of shear thinning fluids can develop
across the wide dimension in rectangular microfluidic channels, with implications
for microfluidic rheometry.
PMID- 28691109
TI - Direct imaging of coexisting ordered and frustrated sublattices in artificial
ferromagnetic quasicrystals.
AB - We have used scanning electron microscopy with polarization analysis and
photoemission electron microscopy to image the two-dimensional magnetization of
permalloy films patterned into Penrose P2 tilings (P2T). The interplay of
exchange interactions in asymmetrically coordinated vertices and short-range
dipole interactions among connected film segments stabilize magnetically ordered,
spatially distinct sublattices that coexist with frustrated sublattices at room
temperature. Numerical simulations that include long-range dipole interactions
between sublattices agree with images of as-grown P2T samples and predict a
magnetically ordered ground state for a two-dimensional quasicrystal lattice of
classical Ising spins.
PMID- 28691110
TI - Optimization of Glutaraldehyde Vapor Treatment for Electrospun Collagen/Silk
Tissue Engineering Scaffolds.
AB - Freestanding fibrous matrices with proper protein composition and desirable
mechanical properties, stability, and biocompatibility are in high demand for
tissue engineering. Electrospun (E-spun) collagen-silk composite fibers are
promising tissue engineering scaffolds. However, as-spun fibers are mechanically
weak and unstable. In this work, we applied glutaraldehyde (GA) vapor treatment
to improve the fiber performance, and the effect on the properties of E-spun
collagen-silk fibers was studied systematically. GA treatment was found to affect
collagen and silk distinctively. Whereas GA chemically links collagen peptides,
it induces conformational transitions to enrich beta-sheets in silk. The combined
effects impose a control of the mechanical properties, stability, and
degradability of the composite fibers, which are dependent on the extent of GA
treatment. In addition, a mild treatment of the fibers did not diminish cell
proliferation and viability. However, overly treated fibers demonstrated reduced
cell-matrix adhesion. The understanding of GA treatment effects on collagen,
silk, and the composite fibers enables effective control and fine tuning of the
fiber properties to warrant their diverse in vitro and in vivo applications.
PMID- 28691111
TI - Density Functional Calculations for Prediction of 57Fe Mossbauer Isomer Shifts
and Quadrupole Splittings in beta-Diketiminate Complexes.
AB - The relative ease of Mossbauer spectroscopy and of density functional theory
(DFT) calculations encourages the use of Mossbauer parameters as a validation
method for calculations, and the use of calculations as a double check on
crystallographic structures. A number of studies have proposed correlations
between the computationally determined electron density at the iron nucleus and
the observed isomer shift, but deviations from these correlations in low-valent
iron beta-diketiminate complexes encouraged us to determine a new correlation for
these compounds. The use of B3LYP/def2-TZVP in the ORCA platform provides an
excellent balance of accuracy and speed. We provide here not only this new
correlation and a clear guide to its use but also a systematic analysis of the
limitations of this approach. We also highlight the impact of crystallographic
inaccuracies, DFT model truncation, and spin states, with intent to assist
experimentalists to use Mossbauer spectroscopy and calculations together.
PMID- 28691112
TI - ALD Al2O3-Coated TiO2 Nanotube Layers as Anodes for Lithium-Ion Batteries.
AB - The utilization of the anodic TiO2 nanotube layers, with uniform Al2O3 coatings
of different thicknesses (prepared by atomic layer deposition, ALD), as the new
electrode material for lithium-ion batteries (LIBs), is reported herein.
Electrodes with very thin Al2O3 coatings (~1 nm) show a superior electrochemical
performance for use in LIBs compared to that of the uncoated TiO2 nanotube
layers. A more than 2 times higher areal capacity is received on these coated
TiO2 nanotube layers (~75 vs 200 MUAh/cm2) as well as higher rate capability and
coulombic efficiency of the charging and discharging reactions. Reasons for this
can be attributed to an increased mechanical stability of the TiO2 nanotube
layers upon Al2O3 coating, as well as to an enhanced diffusion of the Li+ ions
within the coated nanotube layers. In contrast, thicker ALD Al2O3 coatings result
in a blocking of the electrode surface and therefore an areal capacity decrease.
PMID- 28691113
TI - Experimental Errors in QSAR Modeling Sets: What We Can Do and What We Cannot Do.
AB - Numerous chemical data sets have become available for quantitative structure
activity relationship (QSAR) modeling studies. However, the quality of different
data sources may be different based on the nature of experimental protocols.
Therefore, potential experimental errors in the modeling sets may lead to the
development of poor QSAR models and further affect the predictions of new
compounds. In this study, we explored the relationship between the ratio of
questionable data in the modeling sets, which was obtained by simulating
experimental errors, and the QSAR modeling performance. To this end, we used
eight data sets (four continuous endpoints and four categorical endpoints) that
have been extensively curated both in-house and by our collaborators to create
over 1800 various QSAR models. Each data set was duplicated to create several new
modeling sets with different ratios of simulated experimental errors (i.e.,
randomizing the activities of part of the compounds) in the modeling process. A
fivefold cross-validation process was used to evaluate the modeling performance,
which deteriorates when the ratio of experimental errors increases. All of the
resulting models were also used to predict external sets of new compounds, which
were excluded at the beginning of the modeling process. The modeling results
showed that the compounds with relatively large prediction errors in cross
validation processes are likely to be those with simulated experimental errors.
However, after removing a certain number of compounds with large prediction
errors in the cross-validation process, the external predictions of new compounds
did not show improvement. Our conclusion is that the QSAR predictions, especially
consensus predictions, can identify compounds with potential experimental errors.
But removing those compounds by the cross-validation procedure is not a
reasonable means to improve model predictivity due to overfitting.
PMID- 28691114
TI - Structure and Dynamics of Type III Secretion Effector Protein ExoU As determined
by SDSL-EPR Spectroscopy in Conjunction with De Novo Protein Folding.
AB - ExoU is a 74 kDa cytotoxin that undergoes substantial conformational changes as
part of its function, that is, it has multiple thermodynamically stable
conformations that interchange depending on its environment. Such flexible
proteins pose unique challenges to structural biology: (1) not only is it often
difficult to determine structures by X-ray crystallography for all biologically
relevant conformations because of the flat energy landscape (2) but also
experimental conditions can easily perturb the biologically relevant
conformation. The first challenge can be overcome by applying orthogonal
structural biology techniques that are capable of observing alternative,
biologically relevant conformations. The second challenge can be addressed by
determining the structure in the same biological state with two independent
techniques under different experimental conditions. If both techniques converge
to the same structural model, the confidence that an unperturbed biologically
relevant conformation is observed increases. To this end, we determine the
structure of the C-terminal domain of the effector protein, ExoU, from data
obtained by electron paramagnetic resonance spectroscopy in conjunction with site
directed spin labeling and in silico de novo structure determination. Our
protocol encompasses a multimodule approach, consisting of low-resolution
topology sampling, clustering, and high-resolution refinement. The resulting
model was compared with an ExoU model in complex with its chaperone SpcU obtained
previously by X-ray crystallography. The two models converged to a minimal
RMSD100 of 3.2 A, providing evidence that the unbound structure of ExoU matches
the fold observed in complex with SpcU.
PMID- 28691115
TI - Toward a Digital Thread and Data Package for Metals-Additive Manufacturing.
AB - Additive manufacturing (AM) has been envisioned by many as a driving factor of
the next industrial revolution. Potential benefits of AM adoption include the
production of low-volume, customized, complicated parts/products, supply chain
efficiencies, shortened time-to-market, and environmental sustainability. Work
remains, however, for AM to reach the status of a full production-ready
technology. Whereas the ability to create unique 3D geometries has been generally
proven, production challenges remain, including lack of (1) data manageability
through information management systems, (2) traceability to promote product
producibility, process repeatability, and part-to-part reproducibility, and (3)
accountability through mature certification and qualification methodologies. To
address these challenges in part, this paper discusses the building of data
models to support the development of validation and conformance methodologies in
AM. We present an AM information map that leverages informatics to facilitate
part producibility, process repeatability, and part-to-part reproducibility in an
AM process. We present three separate case studies to demonstrate the importance
of establishing baseline data structures and part provenance through an AM
digital thread.
PMID- 28691116
TI - QOL and Survival Comparisons by Race in Oncology Clinical Trials.
AB - BACKGROUND: Significant efforts have been made to increase access and accrual to
clinical trials for minority cancer patients (MP). This meta-analysis looked for
differences in survival and baseline quality of life (QOL) between MP and non
minority cancer patients (NMP). MATERIALS AND METHODS: Baseline QOL and overall
survival times from 47 clinical trials (6513 patients) conducted at Mayo Clinic
Cancer Center/North Central Cancer Treatment Group were utilized. Assessments
included Uniscale, Linear Analogue Self Assessment, Symptom Distress Scale (SDS),
Profile of Mood States and Functional Assessment of Cancer Therapy - General,
each transformed into a 0-100 scale with higher scores indicating better
outcomes. This transformation involves subtracting the lowest possible value from
the assessment, dividing by the range of the scale (the maximum minus the
minimum), and multiplying by 100. Analyses included Fisher's Exact tests, linear
regression, Kaplan-Meier curves, and Cox proportional hazards models. RESULTS:
Eight percent of patients self-reported as MP (0.45% American Indian/Alaskan
Native, 0.7% Asian, 5% Black/African American, 1.5% Hispanic, 0.1% Native
Hawaiian and 0.3% Other). MP had no meaningful deficits relative to non-MP in
overall QOL but were slightly worse on FACT-G total score, physical,
social/family, functional, and SDS nausea severity. MP with lung, neurological or
GI cancers had significantly worse mean scores in nausea (58 vs. 69), sleep
problems (34 vs. 54); emotional (53 vs. 74); and social/family (60 vs. 67),
respectively. Regression models confirmed these results. After adjusting for
disease site, there were no significant differences in survival. CONCLUSION: MP
on these clinical trials indicated small deficits in physical, social, and
emotional subscales at baseline compared to NMP. Within cancer sites, MP
experienced large deficits for selected QOL domains that bear further attention.
PMID- 28691117
TI - Angiotensin-(1-7) and the Regulation of Anti-Fibrotic Signaling Pathways.
PMID- 28691118
TI - Contrast-Enhanced Ultrasound Reveals Exercise-Induced Perfusion Deficits in
Claudicants.
AB - BACKGROUND: Contrast-Enhanced Ultrasonography (CEUS) is an imaging modality
allowing perfusion quantification in targeted regions of interest of the lower
extremity that has not been possible with color-flow imaging or with measurement
of ankle brachial indices. We developed a protocol to quantify lower extremity
muscle perfusion impairment in PAD patients in response to exercise. METHODS AND
FINDINGS: Thirteen patients with Rutherford Class I-III Peripheral Arterial
Disease (PAD) and no prior revascularization procedures were recruited from the
Baltimore Veterans Affairs Medical Center and compared with eight control
patients without PAD. CEUS interrogation of the index limb gastrocnemius muscle
was performed using an intravenous bolus of lipid-stabilized microsphere contrast
before and after a standardized treadmill protocol. Peak perfusion (PEAK) and
time to peak perfusion (TTP) were measured before and after exercise. Between and
within group differences were assessed. Control subjects demonstrated a more
rapid TTP (p<0.01) and an increase in peak perfusion (PEAK, p=0.02) after
exercise, when compared to their baseline measures. Patients with PAD
demonstrated TTP and PEAK measures equivalent to controls at baseline (p=0.39,
p=0.71, respectively). However, they exhibited no significant exercise-induced
changes in perfusion (TTP p=0.49 and PEAK 0.67, respectively compared to
baseline). After exercise, normal subjects had significantly shorter TTP (p=0.04)
and greater PEAK (p=0.02) than PAD patients. CONCLUSION: Consistent with their
lack of ischemic symptoms at rest, class I to III claudicant PAD patients showed
similar perfusion measures (TTP and PEAK) at rest. PAD patients, however, were
unable to increase perfusion in response to exercise, whereas controls increased
perfusion significantly. This corresponds with claudication and limited walking
capacity observed in PAD. CEUS with bolus injection offers a convenient,
objective, quantitative and visual physiologic assessment of perfusion limitation
in specific muscle groups of PAD patients. This has the potential for substantial
clinical and research utility.
PMID- 28691119
TI - A Mobile Food Record For Integrated Dietary Assessment.
AB - This paper presents an integrated dietary assessment system based on food image
analysis that uses mobile devices or smartphones. We describe two components of
our integrated system: a mobile application and an image-based food nutrient
database that is connected to the mobile application. An easy-to-use mobile
application user interface is described that was designed based on user
preferences as well as the requirements of the image analysis methods. The user
interface is validated by user feedback collected from several studies. Food
nutrient and image databases are also described which facilitates image-based
dietary assessment and enable dietitians and other healthcare professionals to
monitor patients dietary intake in real-time. The system has been tested and
validated in several user studies involving more than 500 users who took more
than 60,000 food images under controlled and community-dwelling conditions.
PMID- 28691120
TI - Gaps Analysis of Integrating Product Design, Manufacturing, and Quality Data in
The Supply Chain Using Model-Based Definition.
AB - Advances in information technology triggered a digital revolution that holds
promise of reduced costs, improved productivity, and higher quality. To ride this
wave of innovation, manufacturing enterprises are changing how product
definitions are communicated - from paper to models. To achieve industry's vision
of the Model-Based Enterprise (MBE), the MBE strategy must include model-based
data interoperability from design to manufacturing and quality in the supply
chain. The Model-Based Definition (MBD) is created by the original equipment
manufacturer (OEM) using Computer-Aided Design (CAD) tools. This information is
then shared with the supplier so that they can manufacture and inspect the
physical parts. Today, suppliers predominantly use Computer-Aided Manufacturing
(CAM) and Coordinate Measuring Machine (CMM) models for these tasks.
Traditionally, the OEM has provided design data to the supplier in the form of
two-dimensional (2D) drawings, but may also include a three-dimensional (3D)
shape-geometry model, often in a standards-based format such as ISO 10303
203:2011 (STEP AP203). The supplier then creates the respective CAM and CMM
models and machine programs to produce and inspect the parts. In the MBE vision
for model-based data exchange, the CAD model must include product-and
manufacturing information (PMI) in addition to the shape geometry. Today's CAD
tools can generate models with embedded PMI. And, with the emergence of STEP
AP242, a standards-based model with embedded PMI can now be shared downstream.
The on-going research detailed in this paper seeks to investigate three concepts.
First, that the ability to utilize a STEP AP242 model with embedded PMI for CAD
to-CAM and CAD-to-CMM data exchange is possible and valuable to the overall goal
of a more efficient process. Second, the research identifies gaps in tools,
standards, and processes that inhibit industry's ability to cost-effectively
achieve model-based-data interoperability in the pursuit of the MBE vision.
Finally, it also seeks to explore the interaction between CAD and CMM processes
and determine if the concept of feedback from CAM and CMM back to CAD is
feasible. The main goal of our study is to test the hypothesis that model-based
data interoperability from CAD-to-CAM and CAD-to-CMM is feasible through
standards-based integration. This paper presents several barriers to model-based
data interoperability. Overall, the project team demonstrated the exchange of
product definition data between CAD, CAM, and CMM systems using standards-based
methods. While gaps in standards coverage were identified, the gaps should not
stop industry's progress toward MBE. The results of our study provide evidence in
support of an open-standards method to model-based-data interoperability, which
would provide maximum value and impact to industry.
PMID- 28691121
TI - AUTOMATING ASSET KNOWLEDGE WITH MTCONNECT.
AB - In order to maximize assets, manufacturers should use real-time knowledge
garnered from ongoing and continuous collection and evaluation of factory-floor
machine status data. In discrete parts manufacturing, factory machine monitoring
has been difficult, due primarily to closed, proprietary automation equipment
that make integration difficult. Recently, there has been a push in applying the
data acquisition concepts of MTConnect to the real-time acquisition of machine
status data. MTConnect is an open, free specification aimed at overcoming the
"Islands of Automation" dilemma on the shop floor. With automated asset analysis,
manufacturers can improve production to become lean, efficient, and effective.
The focus of this paper will be on the deployment of MTConnect to collect real
time machine status to automate asset management. In addition, we will leverage
the ISO 22400 standard, which defines an asset and quantifies asset performance
metrics. In conjunction with these goals, the deployment of MTConnect in a large
aerospace manufacturing facility will be studied with emphasis on asset
management and understanding the impact of machine Overall Equipment
Effectiveness (OEE) on manufacturing.
PMID- 28691122
TI - Automated morphological analysis of clinical language samples.
AB - Quantitative analysis of clinical language samples is a powerful tool for
assessing and screening developmental language impairments, but requires
extensive manual transcription, annotation, and calculation, resulting in error
prone results and clinical underutilization. We describe a system that performs
automated morphological analysis needed to calculate statistics such as the mean
length of utterance in morphemes (MLUM), so that these statistics can be computed
directly from orthographic transcripts. Estimates of MLUM computed by this system
are closely comparable to those produced by manual annotation. Our system can be
used in conjunction with other automated annotation techniques, such as maze
detection. This work represents an important first step towards increased
automation of language sample analysis, and towards attendant benefits of
automation, including clinical greater utilization and reduced variability in
care delivery.
PMID- 28691123
TI - Similarity Measures for Quantifying Restrictive and Repetitive Behavior in
Conversations of Autistic Children.
AB - Restrictive and repetitive behavior (RRB) is a core symptom of autism spectrum
disorder (ASD) and are manifest in language. Based on this, we expect children
with autism to talk about fewer topics, and more repeatedly, during their
conversations. We thus hypothesize a higher semantic overlap ratio between
dialogue turns in children with ASD compared to those with typical development
(TD). Participants of this study include children ages 4-8, 44 with TD and 25
with ASD without language impairment. We apply several semantic similarity
metrics to the children's dialogue turns in semi-structured conversations with
examiners. We find that children with ASD have significantly more semantically
overlapping turns than children with TD, across different turn intervals. These
results support our hypothesis, and could provide a convenient and robust ASD
specific behavioral marker.
PMID- 28691124
TI - Measuring Changes in Gait and Vehicle Transfer Ability During Inpatient
Rehabilitation with Wearable Inertial Sensors.
AB - Restoration of functional independence in gait and vehicle transfer ability is a
common goal of inpatient rehabilitation. Currently, ambulation changes tend to be
subjectively assessed. To investigate more precise objective assessment of
progress in inpatient rehabilitation, we quantitatively assessed gait and
transfer performances over the course of rehabilitation with wearable inertial
sensors for 20 patients receiving inpatient rehabilitation services. Secondarily,
we asked physical therapists to provide feedback about the clinical utility of
metrics derived from the sensors. Participant performance was recorded on a
sequence of ambulatory tasks that closely resemble everyday activities. We
developed a custom software system to process sensor signals and compute metrics
that characterize ambulation performance. We quantify changes in gait and
transfer ability by performing a repeated measures comparison of the metrics one
week apart. Metrics showing the greatest improvement are walking speed, stride
regularity, acceleration root mean square, walking smoothness, shank peak angular
velocity, and shank range of motion. Furthermore, feedback from physical
therapists suggests that wearable sensor-derived metrics can potentially provide
rehabilitation therapists with additional valuable information to aid in
treatment decisions.
PMID- 28691125
TI - Quantifying the Impact of Non-coding Variants on Transcription Factor-DNA
Binding.
AB - Many recent studies have emphasized the importance of genetic variants and
mutations in cancer and other complex human diseases. The overwhelming majority
of these variants occur in non-coding portions of the genome, where they can have
a functional impact by disrupting regulatory interactions between transcription
factors (TFs) and DNA. Here, we present a method for assessing the impact of non
coding mutations on TF-DNA interactions, based on regression models of DNA
binding specificity trained on high-throughput in vitro data. We use ordinary
least squares (OLS) to estimate the parameters of the binding model for each TF,
and we show that our predictions of TF-binding changes due to DNA mutations
correlate well with measured changes in gene expression. In addition, by
leveraging distributional results associated with OLS estimation, for each
predicted change in TF binding we also compute a normalized score (z-score) and a
significance value (p-value) reflecting our confidence that the mutation affects
TF binding. We use this approach to analyze a large set of pathogenic non-coding
variants, and we show that these variants lead to significant differences in TF
binding between alleles, compared to a control set of common variants. Thus, our
results indicate that there is a strong regulatory component to the pathogenic
non-coding variants identified thus far.
PMID- 28691126
TI - Automatic detection of pragmatic deficits in children with autism.
AB - Autism spectrum disorder (ASD) is characterized by atypical and idiosyncratic
language, which often has its roots in pragmatic deficits. Identifying and
measuring pragmatic language ability is challenging and requires substantial
clinical expertise. In this paper, we present a method for automatically
identifying pragmatically inappropriate language in narratives using two features
related to relevance and topicality. These features, which are derived using
techniques from machine translation and information retrieval, are able to
distinguish the narratives from children with ASD from those of their language
matched peers and may prove useful in the development of automated screening
tools for autism and neurodevelopmental disorders.
PMID- 28691127
TI - Selenium nanoparticles with low-level ionizing radiation exposure ameliorate
nicotine-induced inflammatory impairment in rat kidney.
AB - Occupational exposure to low-level ionizing radiation (<1 Gy) was shown to
enhance cell protection via attenuating an established inflammatory process.
Nicotine, a major toxic component of cigarette smoke, is responsible for smoking
mediated renal dysfunction. The present study was therefore aimed to investigate
the protective impact of ginger Zingiber officinale selenium nanoparticles
(SeNPs) with whole-body low-dose gamma radiation (gamma-R) against nicotine
induced nephrotoxicity in male albino rats. Nicotine intoxication was induced
with 0.5 mg/kg BW. Rats received 0.1 mg SeNPs/kg BW by gastric gavage concomitant
with 0.5 Gy gamma-R over 4 weeks. Characterization studies showed the formation
of spherical SeNPs with a size ranged from 10 to 30 nm in diameter with a thin
film encapsulating the nanoballs. Our data revealed that nicotine induced renal
dysfunction manifested by significant abnormal levels of kidney function markers
(creatinine, urea, sodium and potassium) accompanied by increased levels of
malondialdehyde along with a reduction in glutathione level, glutathione
peroxidase, and glutathione S-transferase activities. It is worthy to note that
nicotine toxicity induced significant increments in serum inflammatory markers:
tumor necrosis factor-alpha and vascular cell adhesion protein 1. Western
blotting showed marked significant elevation in caspase-3 activities against
nicotine. The mRNA gene expression of inducible cyclooxygenase-2 gene was highly
increased with nicotine intoxication while that of cyclooxygenase-1 did not show
any changes. Interestingly, our data demonstrated that SeNPs in synergistic
interaction with gamma-R are efficacious control against nicotine-induced
nephrotoxicity via anti-oxidant-mediated anti-inflammatory activities. Thus, it
is tempting to recommend dietary approaches with ginger SeNPs for smokers at
workplaces exposed occupationally and regularly to low-level ionizing radiation.
PMID- 28691128
TI - Virulent strain of African swine fever virus eclipses its attenuated derivative
after challenge.
AB - African swine fever (ASF) is one of the most devastating diseases affecting the
swine industry worldwide. No effective vaccine is currently available for disease
prevention and control. Although live attenuated vaccines (LAV) have demonstrated
great potential for immunizing against homologous strains of African swine fever
virus (ASFV), adverse reactions from LAV remain a concern. Here, by using a
homologous ASFV Congo strain system, we show passage-attenuated Congo LAV to
induce an efficient protective immune response against challenge with the
virulent parental Congo strain. Notably, only the parental challenge Congo strain
was identified in blood and organs of recovered pigs through B602L gene PCR, long
range PCR, nucleotide sequencing and virus isolation. Thus, despite the great
protective potential of homologous attenuated ASFV strain, the challenge Congo
strain can persist for weeks in recovered pigs and a recrudescence of virulent
virus at late time post-challenge may occur.
PMID- 28691129
TI - Preponderance of enterovirus C in RD-L20B-cell-culture-negative stool samples
from children diagnosed with acute flaccid paralysis in Nigeria.
AB - Recently, a reverse transcriptase semi-nested polymerase chain reaction (RT
snPCR) assay was recommended by the WHO for direct detection of enteroviruses in
clinical specimens. In this study, we use this assay and a modification thereof
to screen acute flaccid paralysis (AFP) samples that had previously tested
negative for enteroviruses by the RD-L20B algorithm. Thirty paired stool
suspensions collected in 2015 as part of the national AFP surveillance program in
different states of Nigeria were analyzed in this study. The samples had
previously tested negative for enteroviruses in the polio laboratory in
accordance with the WHO-recommended RD-L20B-cell-culture-based algorithm. Two
samples that had previously been found to contain enteroviruses were included as
positive controls. All samples were subjected to RNA extraction, the RT-snPCR
assay and a modified version of the RT-snPCR. All amplicons were sequenced, and
enteroviruses were identified using the enterovirus genotyping tool and
phylogenetic analysis. Amplicons were recovered from the two controls and 50%
(15/30) of the samples screened. Fourteen were successfully typed, of which, 7.1%
(1/14), 21.4% (3/14), 64.3% (9/14) and 7.1% (1/14) were enterovirus (EV) -A, EV
B, EV-C and a mixture of EV-B and C (EV-C99 and E25), respectively. The two
controls were identified as EV-C99 and coxsackievirus (CV) -A1, both of which
belong to the species Enterovirus C. In one sample, poliovirus serotype 2 was
detected and found to have the VP1 ILE143 variation and was therefore identified
as a vaccine strain. The results of this study showed that significant proportion
of enterovirus infections (including some with Sabin PV2) are being missed by the
RD-L20B-cell-culture-based algorithm, thus highlighting the value of the RT-snPCR
assay and its modifications. The circulation and preponderance of EV-C in Nigeria
was also confirmed.
PMID- 28691130
TI - Young and advanced tumor-some 2D electrodynamic distinctions: melanoma and
satellite during a vascular occlusion test: feasibility study.
AB - Conventional methods of electrobioimpedance imaging are not suited for adequate
visualization of the skin electrical impedance landscape (SEL) because they do
not provide high spatial resolution at large enough area of view. The skin
electrodynamics introscopy (SEI) enabled dynamic spectral imaging of the SEL at
32 * 64 mm2 area with 1 mm spatial resolution. The focus of the study was to
investigate the SEL distinguishing features between early and advanced-stage
cancer at the model object of melanoma and its satellite. The analysis of the
test-induced SEL metamorphoses was carried out at the periods of blood-stop and
blood-restoration. It was found that the young tumor could be reliably visualized
and distinguished by its antiphase hypoxia-induced response as compared to that
of the advanced one. In response to the blood-restoration, an appearance of newly
formed SEL clusters pointed out apparently at vascular abnormalities associated
with the tumor. Similar SEL clusterization can be supposedly expected in response
to any other test factors which affect cell permeability or/and blood viscosity.
The proposed approach might be useful for more thorough mapping and staging
malignancies.
PMID- 28691131
TI - A survey of context recognition in surgery.
AB - With the introduction of operating rooms of the future context awareness has
gained importance in the surgical environment. This paper organizes and reviews
different approaches for recognition of context in surgery. Major electronic
research databases were queried to obtain relevant publications submitted between
the years 2010 and 2015. Three different types of context were identified: (i)
the surgical workflow context, (ii) surgeon's cognitive and (iii) technical state
context. A total of 52 relevant studies were identified and grouped based on the
type of context detected and sensors used. Different approaches were summarized
to provide recommendations for future research. There is still room for
improvement in terms of methods used and evaluations performed. Machine learning
should be used more extensively to uncover hidden relationships between different
properties of the surgeon's state, particularly when performing cognitive context
recognition. Furthermore, validation protocols should be improved by performing
more evaluations in situ and with a higher number of unique participants. The
paper also provides a structured outline of recent context recognition methods to
facilitate development of new generation context-aware surgical support systems.
PMID- 28691132
TI - Randomized phase II placebo-controlled study to evaluate the efficacy of topical
pure emu oil for joint pain related to adjuvant aromatase inhibitor use in
postmenopausal women with early breast cancer: JUST (Joints Under Study).
AB - PURPOSE: Aromatase inhibitors are standard of care in women with hormone receptor
positive early breast cancer. Published evidence demonstrates that adverse
effects may have an impact on drug compliance, with arthralgias being one of the
most commonly reported adverse effects. METHODS: Eligible patients were
postmenopausal women who had experienced arthralgia following initiation of an
aromatase inhibitor. Patients who experienced arthralgias following a minimum of
a 3-month treatment on the aromatase inhibitor were randomized to emu oil or
placebo oil. The primary endpoint was to assess for a reduction in pain as
measured by a visual analogue score after 8 weeks of treatment. RESULTS: Seventy
three patients comprised the intent-to-treat population, and there was no
statistically significant benefit with use of EO. However, there was a
statistically significant improvement in pain (visual analogue score was -1.28; p
< 0.001) and Brief Pain Inventory severity score -0.88 (p < 0.001), as well as
functional interference (Brief Pain Inventory interference -1.10 (p < 0.001) for
the entire population following an 8-week administration of EO or placebo oil.
CONCLUSIONS: Arthralgias, as a result of aromatase inhibitor use, may be
ameliorated by the use of topical oil massaged onto the joint. Further research
into interventions for this common side effect is needed.
PMID- 28691133
TI - Sleep quality in long-term survivors of head and neck cancer: preliminary
findings.
AB - PURPOSE: This preliminary study evaluated sleep quality in long-term head and
neck cancer survivors, using demographic data and clinical features of the
cancers as assessment criteria. In addition, a possible correlation was examined
between scores on self-rated questionnaires of sleep quality and assessments of
quality of life and oral health status. METHODS: Subjects were 77 head and neck
cancer survivors. Sleep quality was evaluated using the Pittsburgh Sleep Quality
Index and the Epworth Sleepiness Scale. Oral and general health status was
assessed using The Oral Health Impact Profile (OHIP-14) and the Short-Form Health
Survey (SF-36), respectively, and correlated with clinical parameters. Spearman's
correlation coefficients were calculated to examine relationships between
variables. Logistic regression analysis was performed to identify independent
variables associated with poor sleep quality. RESULTS: Eighty-three percent of
patients had poor sleep quality (global scores >=5) and 40% had a global
Pittsburgh Sleep Quality Index score >=8, indicating significantly poor sleep
quality. Nocturnal enuresis, daytime sleepiness, and early morning awakening were
the most common complaints. Extensive neck dissection, a lower SF-36 mental
component score, and a higher OHIP-14 psychological disability score were
independently associated with poor sleep quality. OHIP-14 global score was linked
independently with daytime sleepiness. CONCLUSION: This is the first study to
demonstrate a high prevalence of poor sleep quality in long-term head and neck
cancer survivors. Extensive neck dissection, poor mental health, and
psychological disability may contribute to poor sleep quality. Maintaining good
oral health-related quality of life could promote better sleep in these patients.
PMID- 28691134
TI - Seizure disorders and developmental disorders: impact on life of affected
families-a structured interview.
AB - : Seizure disorder and developmental disorder are two of the most common chronic
disorders in childhood. Data on perceived parental burden and specific effects on
daily life is scarce. We performed a structured interview, consecutively talking
to all parents of pediatric outpatients of our university hospital diagnosed with
seizure or developmental disorder. Three hundred seven parents (of 317 affected
children: 53 with seizure disorder, 44 with specific developmental disorder, 35
with learning disorder, 71 with intellectual disability, 15 with seizure +
specific developmental disorder, 23 with seizure + learning disorder, 76 with
seizure disorder + intellectual disability) were interviewed. Parents of children
with both seizure disorder and intellectual disability stated the highest
constraints in daily life, regarding friends, hobbies, emotional pressure,
occupation, partnership, habitation, and financial burden. Due to diagnosis of
seizure or developmental disorder, 155/307 (51%) parents reduced their working
hours/stopped working, 62/307 (20%) changed their habitation, and 46/307 (15%)
broke up. As judged by parents, 148/317 (47%) children are being discriminated
against, even own family/friends and educators are held responsible. CONCLUSION:
Parents perceive changes in their daily life and discrimination of their children
due to their children's seizure and developmental disorders. An intellectual
disability combined with seizure disorder caused the highest constraint. What is
Known: * Seizure and/or developmental disorders of children may adversely
influence quality of life for affected parents. * Caring for a child with special
health care needs can take complete attention and own parental needs may
therefore be difficult to meet. What is New: * Two out of three parents stated
changes of their daily life such as quitting work, change of habitation, or
breakup of partnership due to their child's diagnosis. * As judged by the
parents, one in two children with developmental disorder of any kind is being
discriminated against, even teachers and own family are held responsible.
PMID- 28691135
TI - Palm kernel cake obtained from biodiesel production in diets for goats: feeding
behavior and physiological parameters.
AB - The objective of this study was to evaluate the effects of the inclusion of palm
kernel (Elaeis guineensis) cake in diets for goats on feeding behaviors, rectal
temperature, and cardiac and respiratory frequencies. Forty crossbred Boer male,
non-castrated goats (ten animals per treatment), with an average age of 90 days
and an initial body weight of 15.01 +/- 1.76 kg, were used. The goats were fed
Tifton 85 (Cynodon spp.) hay and palm kernel supplemented at the rates of 0, 7,
14, and 21% of dry matter (DM). The feeding behaviors (rumination, feeding, and
idling times) were observed for three 24-h periods. DM and neutral detergent
fiber (NDF) intake values were estimated as the difference between the total DM
and NDF contents of the feed offered and the total DM and NDF contents of the
orts. There was no effect of palm kernel cake inclusion in goat diets on DM
intake (P > 0.05). However, palm kernel cake promoted a linear increase (P <
0.05) in NDF intake and time spent feeding and ruminating (min/day; %; period)
and a linear decrease in time spent idling. Palm kernel cakes had no effects (P >
0.05) on the chewing, feeding, and rumination efficiency (DM and NDF) or on
physiological variables. The use up to 21% palm kernel cake in the diet of
crossbred Boer goats maintained the feeding behaviors and did not change the
physiological parameters of goats; therefore, its use is recommended in the diet
of these animals.
PMID- 28691136
TI - Estimates of direct and maternal (co)variance components as well as genetic
parameters of growth traits in Nellore sheep.
AB - In the present study, (co)variance components and genetic parameters in Nellore
sheep were obtained by restricted maximum likelihood (REML) method using six
different animal models with various combinations of direct and maternal genetic
effects for birth weight (BW), weaning weight (WW), 6-month weight (6MW), 9-month
weight (9MW) and 12-month weight (YW). Evaluated records of 2075 lambs descended
from 69 sires and 478 dams over a period of 8 years (2007-2014) were collected
from the Livestock Research Station, Palamaner, India. Lambing year, sex of lamb,
season of lambing and parity of dam were the fixed effects in the model, and ewe
weight was used as a covariate. Best model for each trait was determined by log
likelihood ratio test. Direct heritability for BW, WW, 6MW, 9MW and YW were 0.08,
0.03, 0.12, 0.16 and 0.10, respectively, and their corresponding maternal
heritabilities were 0.07, 0.10, 0.09, 0.08 and 0.11. The proportions of maternal
permanent environment variance to phenotypic variance (Pe2) were 0.07, 0.10,
0.07, 0.06 and 0.10 for BW, WW, 6MW, 9MW and YW, respectively. The estimates of
direct genetic correlations among the growth traits were positive and ranged from
0.44(BW-WW) to 0.96(YW-9MW), and the estimates of phenotypic and environmental
correlations were found to be lower than those of genetic correlations. Exclusion
of maternal effects in the model resulted in biased estimates of genetic
parameters in Nellore sheep. Hence, to implement optimum breeding strategies for
improvement of traits in Nellore sheep, maternal effects should be considered.
PMID- 28691137
TI - Effective use of balloon guide catheters in reducing incidence of mechanical
thrombectomy related distal embolization.
AB - BACKGROUND AND PURPOSE: The clinical benefit of endovascular stroke therapy has
been demonstrated in several prospective randomized trials. However, in a
relevant percentage of patients, mechanical thrombectomy bears the risk of
causing new infarction in initially unaffected vascular territories through
thrombus fragmentation and migration of clot debris. The goal of this study was
to evaluate the use of the balloon guide catheter (BGC) to effectively achieve
flow arrest and thrombus aspiration during the intervention to avoid distal
embolization. METHODS: A retrospective study was performed in 139 patients
between October 2010 and May 2016 to analyze occlusions in the middle cerebral
artery (MCA) or internal carotid artery (ICA) by using a stent retriever with a
BGC (n = 73) or a non-BGC (n = 66). The following data were collected: patient
age and gender, along with history of diabetes mellitus, hypertension, atrial
fibrillation, smoking, obesity, dyslipidemia, and previous ischemic stroke. Data
on procedure time, number of passes, and angiographic findings were also
collected. The final reperfusion score was rated based on the Thrombolysis in
Cerebral Infarction (TICI) grading scale. Successful recanalization was defined
as TICI 3 or 2b. RESULTS: A total of 139 patients underwent mechanical
thrombectomy with the stent retriever. Of the 139 patients, 73 (52.5%) underwent
placement of a BGC. The mean age was 65.8 +/- 13.5 years, and the median National
Institutes of Health Stroke Scale (NIHSS) score was 11. The average initial NIHSS
score was lower in the BGC group compared with the non-BGC group (mean, 11.2 +/-
5.6 vs. 13.2 +/- 5.6; P = 0.03). Patients with BGC had fewer incidences of
previous ischemic stroke (12.3% vs. 28.8%; P = 0.01). The numbers of passes were
similar between the two groups. The procedure time (99 +/- 49.4 min vs. 124 +/-
72.2 min; P = 0.02) and the time from onset of symptoms to procedure end (302 +/-
102 min vs. 357.2 +/- 136.1 min; P = 0.009) were shorter in the BGC group. TICI 3
or 2b recanalization scores were higher in the BGC group compared to the non-BGC
group [63/73, 86.3% vs. 48/66, 72.7%; odds ratio (OR), 0.6; 95% confidence
interval (CI), 0.2-1.4; P = 0.04]. Importantly, distal embolization was less
frequent in the BGC group (5/73, 6.8% vs. 21/66, 31.8%; OR, 6.3; 95% CI, 2.2
18.0; P < 0.001). CONCLUSIONS: The risk of distal embolization was significantly
decreased with the use of a BGC.
PMID- 28691138
TI - The Importance of Parameters: MPV, MPV/Thrombocyte Ratio and
Neutrophil/Lymphocyte Ratio in Sorafenib Treatment Response of Patients with
Hepatocellular Cancer.
PMID- 28691139
TI - Systematic Review and Meta-analysis: Use of Statins Is Associated with a Reduced
Incidence of Oesophageal Adenocarcinoma.
AB - PURPOSE: Laboratory studies have suggested that statins may have useful anti
cancer effects against Barrett's epithelial cancer lines. A variety of effects
have been reported in clinical studies. METHODS: We performed a systematic review
and meta-analysis of the association between statin use and the development of
oesophageal cancer. Multiple databases were searched for studies reporting the
association of statin use and oesophageal cancer. Meta-analysis on the
relationship between statin use and cancer incidence was performed. RESULTS:
Twenty publications met eligibility criteria, yielding 22 datasets for meta
analysis. All were observational studies. Population-level studies included
372,206 cancer cases and 6,086,906 controls. Studies examining adenocarcinoma
development in Barrett's oesophagus included 1057 cancers and 17,741 controls. In
patients with Barrett's oesophagus, statin use was associated with a reduced
incidence of adenocarcinoma (pooled adjusted odds ratio (OR) 0.59 (95% confidence
intervals 0.50-0.68)), with no heterogeneity between 11 studies. Population-based
studies demonstrated more heterogeneity but showed that statin use was associated
with a lower incidence of both oesophageal adenocarcinoma (OR 0.57 (0.43-0.76))
and all oesophageal cancers (OR 0.82 (0.7-0.88)). Information on statin type,
dose, and duration was reported too infrequently for statistical analysis but
individual studies showed a tendency to a dose- and duration-dependant decrease
in cancer incidence. CONCLUSIONS: Statin use is associated with a significantly
lower incidence of oesophageal adenocarcinoma. This is seen in both Barrett's
cohorts and general populations. Further studies should focus on drug, dose, and
duration and the interaction with other risk and preventative factors.
PMID- 28691140
TI - Preclinical and Clinical Evidence on Ipsilateral Corticospinal Projections:
Implication for Motor Recovery.
AB - Motor impairment is the most common complication after stroke, and recovery of
motor function has been shown to be dependent on the extent of lesion in the
ipsilesional corticospinal tract (iCST) and activity within ipsilesional primary
and secondary motor cortices. However, work from neuroimaging research has
suggested a role of the contralesional hemisphere in promoting recovery after
stroke potentially through the ipsilateral uncrossed CST fibers descending to
ipsilateral spinal segments. These ipsilateral fibers, sometimes referred to as
"latent" projections, are thought to contribute to motor recovery independent of
the crossed CST. The aim of this paper is to evaluate using cumulative evidence
from animal models and human patients on whether an uncrossed CST component is
present in mammals and conserved through primates and humans, and whether iCST
fibers have a functional role in hemiparetic/hemiplegic human conditions. This
review highlights that an ipsilateral uncrossed CST exists in human during
development, but the evidence on a functionally relevant iCST component in adult
humans is still elusive. In addition, this review argues that whereas activity
within the ipsilesional cortex is essential for enhancing motor recovery after
stroke, the role of iCST projections specifically is still controversial.
Finally, conclusions from current literature emphasize the importance of activity
in the ipsilesional cortex and the integrity of crossed CST fibers as major
determinants of motor recovery after brain injury.
PMID- 28691141
TI - Vinpocetine Inhibits NF-kappaB-Dependent Inflammation in Acute Ischemic Stroke
Patients.
AB - : Immunity and inflammation play critical roles in the pathogenesis of acute
ischemic stroke. Therefore, immune intervention, as a new therapeutic strategy,
is worthy of exploration. Here, we tested the inflammation modulator,
vinpocetine, for its effect on the outcomes of stroke. For this multi-center
study, we recruited 60 patients with anterior cerebral circulation occlusion and
onset of stroke that had exceeded 4.5 h but lasted less than 48 h. These
patients, after random division into two groups, received either standard
management alone (controls) or standard management plus vinpocetine (30 mg per
day intravenously for 14 consecutive days, Gedeon Richter Plc., Hungary).
Vinpocetine treatment did not change the lymphocyte count; however, nuclear
factor kappa-light-chain-enhancer of activated B cell activation was inhibited as
seen not only by the increased transcription of IkappaBalpha mRNA but also by the
impeded phosphorylation and degradation of IkappaBalpha and subsequent induction
of pro-inflammatory mediators. These effects led to significantly reduced
secondary lesion enlargement and an attenuated inflammation reaction. Compared to
controls, patients treated with vinpocetine had a better recovery of neurological
function and improved clinical outcomes during the acute phase and at 3-month
follow-up. These findings identify vinpocetine as an inflammation modulator that
could improve clinical outcomes after acute ischemic stroke. This study also
indicated the important role of immunity and inflammation in the pathogenesis of
acute ischemic stroke and the significance of immunomodulatory treatment.
CLINICAL TRIAL REGISTRATION INFORMATION: www.clinicaltrials.gov . Identifier:
NCT02878772.
PMID- 28691142
TI - Force level of small diameter nickel-titanium orthodontic wires ligated with
different methods.
AB - BACKGROUND: The aim of this study was to compare the deflection force in
conventional and thermally activated nickel-titanium (NiTi) wires in passive
(Damon Q) and active (Bioquick) self-ligating brackets (SLB) and in conventional
brackets (CB) tied by two different methods: elastomeric ligature (EL) and metal
ligature (ML). METHODS: Two wire diameters (0.014 and 0.016 in.) and 10 specimens
per group were used. The specimens were assembled in a clinical simulation device
and tested in an Instron Universal Testing Machine, with a load cell of 10 N. For
the testing procedures, the acrylic block representative of the right maxillary
central incisor was palatally moved, with readings of the force at 0.5, 1, 2, and
3 mm, at a constant speed of 2 mm/min and temperature of 36.5 degrees C.
RESULTS: The conventional NiTi released higher forces than the thermally
activated NiTi archwires in large deflections. In general, the SLB showed lower
forces, while the ML had higher forces, with both showing a similar force release
behavior, constantly decreasing as the deflection decreased. The EL showed an
irregular behavior. The active SLB showed smaller forces than passive, in large
deflections. CONCLUSIONS: The SLB and the ML exhibit standard force patterns
during unloading, while the elastomeric ligatures exhibit a randomly distributed
force release behavior.
PMID- 28691143
TI - Meningeal haemangiopericytoma and solitary fibrous tumour: a retrospective bi
centre study for outcome and prognostic factor assessment.
AB - To describe the outcome of patients diagnosed with central nervous system
haemangiopericytoma (HPC) or solitary fibrous tumour (SFT) and identify factors
that may influence recurrence and survival. Between January 2000 and September
2016, a retrospective search identified 55 HPCs/SFTs. The patients underwent a
total of 101 surgical resections and 56.9% received radiation therapy. Median
follow-up was 7.8 years. 28 patients (50.9%) were re-operated for tumour
recurrence. At the end of the study, 21 patients (42%) had no residual tumour on
the last scan. Surgical recurrence-free survival at 5 years was 75.2%, 95% CI
[63.3-89.3] and, the median surgical recurrence-free survival was 7.4 years. In
the adjusted analysis, venous sinus invasion (present vs. absent) (HR 3.39, 95%
CI [1.16, 9.93], p = 0.026), completeness of resection (HR 0.38, 95% CI [0.15
0.97], p = 0.042) and tumour subtype (SFT vs. HPC) (HR 3.02, 95% CI[1.02, 8.91],
p = 0.045) were established as independent prognostic factors. At the end of the
study, 25 patients were deceased (45.5%). and only 15 patients (27.3%) had no
residual tumour on the last scan and were alive. Overall survival at 5 years was
80.2, 95% CI [69.3-92.8] and the median overall survival was 13.1 years. None of
the investigated variables was associated with overall survival. Patients who
received radiation therapy demonstrated neither a reduced risk of surgical
recurrence (p = 0.370) nor a longer overall survival (p = 1.000). SFTs/HPCs are
associated with a significant risk of recurrence that may reduce the survival of
the patients. Total tumour resection upon initial surgery is associated with a
lower risk of relapse but not with a prolonged survival. We did not observe a
significant improvement in any of the clinical outcomes after radiation therapy.
PMID- 28691144
TI - Risk of vascular injury when screw drilling for tibial tuberosity transfer.
AB - PURPOSE: During tibial tubercle transfer, popliteal vessels are at risk from
drills and screws. The risk is around 0.11%, as described in the literature. We
reviewed knee injected CT scan for analysis of the location of arteries,
identified landmarks allowing minimizing risks, and defined a safe zone. MATERIAL
AND METHOD: Distances between the posterior cortex and arteries were measured on
CT scans from 30 adults (60 knees) at three levels (proximal part of the tibial
tuberosity, 20 mm and 40 mm distally). Data were used to create a "risk map" with
different angular sectors where the frequency of the presence of arteries was
analyzed in each area. We also analyzed the position of 68 screws of 47 patients
who underwent a medial tibial tuberosity transfer. RESULTS: The nearest distance
between artery and the posterior tibial cortex was found at the level
corresponding to the top of the tuberosity with less than 1 mm, while the largest
distance was found at the distal level. We were able to define a safe zone for
drilling through the posterior tibial cortex which allows a safe fixation for the
screws. This zone corresponds to the medial third of the posterior cortex. When
the safe zone is not respected, screws that overtake the posterior cortex may be
close to arteries as observed for 37 of the 68 screws analyzed. CONCLUSION: We
described new landmarks and recommendations to avoid this complication during
tibial tuberosity transfer.
PMID- 28691146
TI - Expanding the Cultural Adaptation Framework for Population-Level Impact.
AB - Attention to cultural diversity and cultural adaptation of evidence-based
interventions (EBIs) has been a longstanding priority in prevention science.
However, EBIs for diverse populations present several challenges for broad
dissemination and population impact. The five papers in this special issue
underscore some of these challenges and offer new ways of thinking and
recommendations for the next generation of type 2 translation research. This
commentary underscores three broad recommendations, including the need for a more
expanded conceptualization and empirical understanding of the core tension
between fidelity and adaptation; greater focus on the systems of care that
deliver EBIs to culturally diverse populations, including increased attention to
such issues as access and engagement; and greater flexibility in strategies to
adapt and evaluate interventions within and across communities and settings that
serve diverse populations. By offering exemplars and suggestions to address these
challenges, these papers collectively help to realign research on cultural
adaptation with its ultimate goal of reducing health disparities by ensuring
greater access, impact, and equity of prevention services in a dynamic,
multicultural society. However, other fundamental challenges remain unaddressed,
including the need to reduce inequalities that exist in the health, education,
social service, and justice systems that will ultimately support broad diffusion
of EBIs for diverse populations.
PMID- 28691145
TI - The effect of saliva on the fate of nanoparticles.
AB - OBJECTIVES: The design of nanocarriers for local drug administration to the
lining mucosa requires a sound knowledge of how nanoparticles (NPs) interact with
saliva. This contact determines whether NPs agglomerate and become immobile due
to size- and interaction-filtering effects or adsorb on the cell surface and are
internalized by epithelial cells. The aim of this study was to examine the
behavior of NPs in saliva considering physicochemical NP properties. MATERIALS
AND METHODS: The salivary pore-size distribution was determined, and the
viscosity of the fluid inside of the pores was studied with optical tweezers.
Distinct functionalized NPs (20 and 200 nm) were dispersed in saliva and salivary
buffers and characterized, and surface-bound MUC5B and MUC7 were analyzed by 1D
electrophoresis and immunoblotting. NP mobility was recorded, and cellular uptake
studies were performed with TR146 cells. RESULTS: The mode diameter of the
salivary mesh pores is 0.7 MUm with a peak width of 1.9 MUm, and pores are filled
with a low-viscosity fluid. The physicochemical properties of the NPs affected
the colloidal stability and mobility: compared with non-functionalized particles,
which did not agglomerate and showed a cellular uptake rate of 2.8%,
functionalized particles were immobilized, which was correlated with
agglomeration and increased binding to mucins. CONCLUSION: The present study
showed that the salivary microstructure facilitates NP adsorption. However, NP
size and surface functionalization determine the colloidal stability and cellular
interactions. CLINICAL RELEVANCE: The sound knowledge of NP interactions with
saliva enables the improvement of current treatment strategies for inflammatory
oral diseases.
PMID- 28691147
TI - Gastric bypass simultaneously improves adipose tissue function and insulin
dependent type 2 diabetes mellitus.
AB - OBJECTIVE: The underlying causes of type 2 diabetes (T2DM) remain poorly
understood. Adipose tissue dysfunction with high leptin, inflammation, and
increased oxidative stress may play a pivotal role in T2DM development in obese
patients. Little is known about the changes in the adipose tissue after Roux-Y
gastric bypass (RYGB) in non-severely obese patients (BMI < 35 kg/m2) and since
these patients have more T2DM-associated complications than obese patients
("obesity paradox"), we investigated changes in adipose tissue function in a
cohort of BMI <35 kg/m2 with insulin-dependent T2DM after RYGB surgery which
resolves T2DM. METHODS: Twenty patients with insulin-dependent T2DM and BMI <35
kg/m2 underwent RYGB. Insulin-resistance, leptin, oxidative stress, and cytokines
were determined over 24 months. Expression of cytokines and NF-kappaB pathway
genes were measured in leukocytes (PBMC). Adipose tissue inflammation was
examined histologically preoperatively and 24 months after RGYB in subcutaneous
adipose tissue. RESULTS: Insulin-resistance, leptin, oxidative stress as well as
adipose tissue inflammation decreased significantly after RYGB. Similarly,
systemic inflammation was reduced and peripheral blood mononuclear cells (PBMCs)
were reprogrammed towards an M2-type inflammation. Loss of BMI correlated with
leptin levels (r = 0.891, p < 0.0001), insulin resistance (r = 0.527, p = 0.003),
and oxidative stress (r = 0.592, p = 0.016). Leptin correlated with improved
insulin resistance (r = 0.449, p = 0.032) while reduced leptin showed a strong
association with improved oxidative stress (r = 0.809, p = 0.001). Lastly,
reduced oxidative stress correlated strongly with improved insulin-resistance (r
= 0.776, p = 0.001). CONCLUSIONS: RYGB improves adipose tissue function and
inflammation. Leptin as marker for adipose tissue dysfunction may be the
mediating factor between insulin resistance and oxidative stress and thereby
likely improving T2DM.
PMID- 28691149
TI - 12th annual LC/MS/MS workshop on environmental applications and food safety, 5-6
July 2016, Barcelona, Spain.
PMID- 28691148
TI - Entomotoxicology in burnt bodies: a case of maternal filicide-suicide by fire.
AB - One of the most common methods of maternal filicide is by fire. In this case
study, a 40-year-old female and her children were found completely burned in a
burnt out car. All bodies showed a degree of destruction by fire consisting to a
level 3 of the Crow-Glassman Scale (CGS) and early stage of insect activity.
Toxicological analyses were performed on soft tissues and body fluids still
available. The results were positive for diazepam and its metabolites only for
children with blood concentrations consistent with therapeutic doses of
benzodiazepines. Home video surveillance cameras confirmed sedation prior to
death recording the mother while administering some drops of sedative drugs in a
soft drink to the children just a couple of hours before setting fire to the car.
Based on autopsy findings, all victims were still alive at the time of fire. The
cause of death was determined as carbon monoxide poisoning and fatal thermal
injuries by fire. This case study has a special focus on the entomotoxicology and
the potential role of insects in death investigations of burnt bodies, supposed
to be an inadequate substratum for insect colonization. It demonstrates that in
burnt bodies, arthropod colonization can be quite immediate after fire is
extinguished. Toxicological analyses performed on larvae actively feeding on the
children's bodies were positive for diazepam and its metabolites in small amount
compared with blood concentrations, whereas the larvae collected from the
mother's body were totally negative. These data, according to the autopsy
findings and the toxicological results from the victim's blood and tissues,
supported the suspect of a non-lethal sedation prior to death, which is a common
behaviour in maternal filicide.
PMID- 28691150
TI - Quantitative analysis of total starch content in wheat flour by reaction
headspace gas chromatography.
AB - This paper proposed a new reaction headspace gas chromatographic (HS-GC) method
for efficiently quantifying the total starch content in wheat flours. A certain
weight of wheat flour was oxidized by potassium dichromate in an acidic condition
in a sealed headspace vial. The results show that the starch in wheat flour can
be completely transferred to carbon dioxide at the given conditions (at 100
degrees C for 40 min) and the total starch content in wheat flour sample can be
indirectly quantified by detecting the CO2 formed from the oxidation reaction.
The data showed that the relative standard deviation of the reaction HS-GC method
in the precision test was less than 3.06%, and the relative differences between
the new method and the reference method (titration method) were no more than
8.90%. The new reaction HS-GC method is automated, accurate, and can be a
reliable tool for determining the total starch content in wheat flours in both
laboratory and industrial applications. Graphical abstract The total starch
content in wheat flour can be indirectly quantified by the GC detection of the
CO2 formed from the oxidation reaction between wheat flour and potassium
dichromate in an acidic condition.
PMID- 28691151
TI - Integrated and global pseudotargeted metabolomics strategy applied to screening
for quality control markers of Citrus TCMs.
AB - Traditional Chinese medicine (TCM) exerts its therapeutic effect in a holistic
fashion with the synergistic function of multiple characteristic constituents.
The holism philosophy of TCM is coincident with global and systematic theories of
metabolomics. The proposed pseudotargeted metabolomics methodologies were
employed for the establishment of reliable quality control markers for use in the
screening strategy of TCMs. Pseudotargeted metabolomics integrates the advantages
of both targeted and untargeted methods. In the present study, targeted
metabolomics equipped with the gold standard RRLC-QqQ-MS method was employed for
in vivo quantitative plasma pharmacochemistry study of characteristic prototypic
constituents. Meanwhile, untargeted metabolomics using UHPLC-QE Orbitrap HRMS
with better specificity and selectivity was employed for identification of
untargeted metabolites in the complex plasma matrix. In all, 32 prototypic
metabolites were quantitatively determined, and 66 biotransformed metabolites
were convincingly identified after being orally administered with standard
extracts of four labeled Citrus TCMs. The global absorption and metabolism
process of complex TCMs was depicted in a systematic manner.
PMID- 28691152
TI - Reduced BUCY 2 and G-CSF-primed bone marrow associates with low graft-versus-host
disease and transplant-related mortality in allogeneic HSCT.
AB - Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the ideal
treatment for several diseases. However, the morbidity and mortality associated
with the procedure might limit its widespread use; therefore, we implemented
reduced BUCY2 as conditioning method along with the use of G-CSF-primed bone
marrow (G-BM) in order to reduce complications, including graft-versus-host
disease (GVHD), and to improve survival in these patients. An analysis of
transplant characteristics, complications, and survival of patients undergoing an
allo-HSCT using this conditioning regimen (busulfan 12 mg/kg and cyclophosphamide
80 mg/kg) plus G-BM was performed. Forty patients were included from 1999 to
2015. All of them had a HLA-matched donor, with a median age of 32 years (range
16-59), and 55% were male. The most frequent diagnosis was myelodysplastic
syndrome (MDS) in 14 patients (35%), followed by acute lymphoid leukemia (ALL) in
12 (30%). The mean of CD34+ was 2.09 * 106/kg. The mean time to neutrophil and
platelet recovery was 20 and 18 days, respectively. The most common toxicity was
mucositis (75%) with grade III-IV in 53% of cases. Acute GVHD appeared in 12.5
and 35% of patients developed chronic GVHD. Transplant-related mortality (TRM)
was 10%. Five-year relapse-free survival was 69%, and the 5-year overall survival
was 69.5%. Our conditioning method along with G-BM preserves an immunosuppressive
and myeloablative effect allowing eradication of the malignant clone and
achieving adequate bone marrow engraftment with acceptable toxicity, low
incidence of GVHD, and low TRM, representing a favorable alternative for allo
HSCT.
PMID- 28691153
TI - Telomere shortening, TP53 mutations and deletions in chronic lymphocytic leukemia
result in increased chromosomal instability and breakpoint clustering in
heterochromatic regions.
AB - Complex karyotypes are associated with a poor prognosis in chronic lymphocytic
leukemia (CLL). Using mFISH, iFISH, and T/C-FISH, we thoroughly characterized 59
CLL patients regarding parameters known to be involved in chromosomal
instability: status of the genes ATM and TP53 and telomere length. Interestingly,
a deletion of the ATM locus in 11q, independent of the cytogenetic context, was
associated with significantly diminished risk (p<0.05) of carrying a mutation in
TP53. In patients with loss or mutation of TP53, chromosomal breakage occurred
more frequently (p<0.01) in (near-) heterochromatic regions. Median telomere
length in patients with complex karyotypes was significantly shorter than that of
healthy controls and shorter than in all other cytogenetic cohorts. Furthermore,
the median telomere length of patients carrying a TP53 mutation was significantly
shorter than without mutation. We conclude that telomere shortening in
combination with loss of TP53 induces increased chromosomal instability with
preferential involvement of (near-) heterochromatic regions.
PMID- 28691154
TI - Digestive enzyme ratios are good indicators of hatchling yolk reserve and
digestive gland maturation in early life stages of cuttlefish Sepia officinalis
L.: application of these new tools in ecology and aquaculture.
AB - In Sepia officinalis (Linnaeus, 1758), the digestive gland matures during the
first month post-hatching, while a shift from intracellular acid to extracellular
alkaline digestion occurs. The purpose of this study was to investigate the
possibility of using enzymatic ratios for the description of digestive system
maturation in early life stages of S. officinalis. Second, it is intended to
apply these new tools as eco-physiological indicators for understanding the
impact of cuttlefish eggs' life history from different spawning sites of the
English Channel on digestive performance of juveniles. An experimental rearing
was performed over 35 days after hatching (DAH) on juveniles from wild collected
eggs in 2010 and 2011. Four digestive enzyme activities and their ratios [i.e.,
trypsin, cathepsin, acid (ACP), and alkaline (ALP) phosphatase, ALP/ACP, and
trypsin/cathepsin] were studied along with histological features (e.g., internal
yolk surface and digestive gland development). The two enzyme ratios were good
indicators of digestive system maturation allowing the study of the digestive
gland's development. They were highly correlated to juveniles' weight increase
and histological features of the gland in early DAH. These ratios described more
accurately the shift occurring between the intracellular acid and the
extracellular alkaline modes of digestion in S. officinalis and were more
specific than separated enzyme activities. Their application as eco-physiological
tools revealed that enzyme ratios reflected yolk content and digestive gland
development in new hatching juveniles. Finally, ALP/ACP ratio was shown to be a
powerful tool to describe growth performance of S. officinalis which is useful
for aquaculture optimization.
PMID- 28691155
TI - Construction of a novel synthetic root-specific promoter and its characterization
in transgenic tobacco plants.
AB - Synthetic promoter technology offers a framework for designing expression
cassettes that could provide precise control of transgene expression. Such
artificially designed promoters enable defined transgene regulation, reduce
unwanted background expression, and can overcome homology-dependent gene
silencing in transgenic plants. In the present study, a synthetic root-specific
module was designed using characterized cis-acting elements, fused with minimal
promoter (86 bp) from PortUbi882 promoter, and cloned in pCAMBIA1305.1 by
replacing CaMV 35S promoter so as to drive GUS expression. Two constructs were
made; one had the synthetic module at the 5' end of the minimal promoter (SynR1),
whereas in the other construct, the module was present in both 5' and 3' ends
(SynR2). Furthermore, the synthetic promoter constructs were transformed in
tobacco wherein SynR1 promoter drove constitutive expression, whereas SynR2
conferred root-specific expression though slight leaky expression was present in
stem. GUS assay in the roots of transgenic tobacco plants (T1) indicated that
SynR2 promoter expressed significantly higher GUS activity than the CaMV 35S
promoter. The real-time quantitative PCR (RT-qPCR) analysis of GUS gene further
confirmed that SynR2 promoter conferred 2.1-fold higher root-specific expression
when compared to CaMV 35S promoter.
PMID- 28691156
TI - Aquatic exercise for adults with type 2 diabetes: a meta-analysis.
AB - AIMS: The purpose of this systematic review and meta-analysis was to examine the
effects of aquatic exercise (AquaEx) on indicators of glycemic control (i.e.,
glycated hemoglobin [A1c] and fasting plasma glucose) in adults with type 2
diabetes mellitus (T2DM). It was hypothesized that AquaEx would improve glycemic
control to a similar extent as land-based exercise (LandEx), but to a greater
extent than non-exercise control (Ctrl). METHODS: A literature search was
completed in February 2017 for studies examining AquaEx training in adults with
T2DM. Assessment of glycemic control was necessary for inclusion, while secondary
outcomes such as quality of life and cardiometabolic risk factors (i.e., blood
pressure, triglycerides and total cholesterol) were considered, but not required
for inclusion. Outcomes were measured before and after at least 8 weeks of
AquaEx, and data were analyzed using weighted mean differences (WMDs) and fixed
effect models, when appropriate. RESULTS: Nine trials including 222 participants
were identified. Three trials compared AquaEx to LandEx, two compared AquaEx to
Crtl, and four had a pre-/post-design without a comparison group. Results
indicate no difference in A1c between LandEx and AquaEx (WMD = -0.02%, 95%
confidence interval = [-0.71, 0.66]). Post-intervention A1c was lower in AquaEx
when compared to Crtl (WMD = -0.96%, [-1.87, -0.05]). Post-AquaEx A1c was lower
compared to baseline (WMD = -0.48%, [-0.66, -0.30]). CONCLUSIONS: A1c can be
reduced after eight-twelve weeks of AquaEx. However, at this time few studies
have examined whether changes in A1c are different from LandEx or Crtl.
PMID- 28691157
TI - Effect of vigabatrin on seizure control and safety profile in different subgroups
of children with epilepsy.
AB - OBJECTIVE: To evaluate the efficacy and safety of vigabatrin in pediatric
epilepsy. METHODS: We retrospectively reviewed patients with epilepsy treated
with vigabatrin over a 2-year period at a pediatric tertiary center. We assessed
the relationship between seizure frequency, etiology, vigabatrin dose, adverse
events, medication discontinuation reasons, and electroencephalography (EEG)
characteristics. RESULTS: One hundred three patients followed at Boston
Children's Hospital were treated with vigabatrin and had complete medical
records. Within the follow-up interval, 69 (67%) of 103 patients had discontinued
vigabatrin therapy. Two patients (1.9%) died during therapy for unknown reasons.
Median age at vigabatrin initiation was 8 months (interquartile range [IQR] 5
15). Median starting dose was 48.1 mg/kg per day (IQR 29.8-52.3) with a median
target of 100 mg/kg (IQR 81.9-107.9). Median treatment duration was 12.1 months
(n = 89, IQR 5.0-22.9) overall, and 13.3 months (IQR 5.2-23.2) for patients who
discontinued vigabatrin. The most common reasons for discontinuation were
controlled seizures in 31 (43.7%) of 71 and unsatisfactory therapeutic effect in
23 (32.4%) of 71. Median percent seizure reduction from baseline to first follow
up was 83.3% (IQR 27.4-99.8) and 96.7% (IQR 43.3-100) to last follow-up. Twenty
four (38.7%) of 62 patients with a follow-up posttreatment remained seizure-free.
Four patients who had initially achieved seizure freedom relapsed. Patients with
structural/metabolic etiology had greater median percent seizure reduction at
first follow-up than patients with genetic etiology (98.7% vs. 61.4%,
respectively, p = 0.001). Hypsarrhythmia resolved after therapy in 18 of 20 (90%,
95% confidence interval [CI] 70-97) patients with pretreatment hypsarrhythmia,
and 2 patients presented with hypsarrhythmia posttreatment. Risk of having
hypsarrhythmia was reduced by 32% (95% CI 14.9-49.1) posttreatment. SIGNIFICANCE:
Vigabatrin is efficacious in all seizure types and resolved hypsarrhythmia in
most patients. In this series with a median treatment duration of 12.1 months,
vigabatrin had a good safety profile with a low rate of discontinuation due to
nonophthalmologic and ophthalmologic adverse effects.
PMID- 28691158
TI - Anticonvulsant effect of cannabinoid receptor agonists in models of seizures in
developing rats.
AB - OBJECTIVE: Although drugs targeting the cannabinoid system (e.g., CB1 receptor
agonists) display anticonvulsant efficacy in adult animal models of
seizures/epilepsy, they remain unexplored in developing animal models. However,
cannabinoid system functions emerge early in development, providing a rationale
for targeting this system in neonates. We examined the therapeutic potential of
drugs targeting the cannabinoid system in three seizure models in developing
rats. METHODS: Postnatal day (P) 10, Sprague-Dawley rat pups were challenged with
the chemoconvulsant methyl-6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate
(DMCM) or pentylenetetrazole (PTZ), after treatment with either CB1/2 mixed
agonist (WIN 55,212-2), CB1 agonist (arachidonyl-2'-chloroethylamide [ACEA]), CB2
agonist (HU-308), CB1 antagonist (AM-251), CB2 antagonist (AM-630), fatty acid
amide hydrolase inhibitor (URB-597), or G protein-coupled receptor 55 agonist (O
1602). P20 Sprague-Dawley pups were challenged with DMCM after treatment with
WIN, ACEA, or URB. Finally, after pretreatment with WIN, P10 Sprague-Dawley rats
were challenged against acute hypoxia-induced seizures. RESULTS: The mixed CB1/2
agonist and the CB1-specific agonist, but no other drugs, displayed
anticonvulsant effects against clonic seizures in the DMCM model. By contrast,
both CB1 and CB2 antagonism increased seizure severity. Similarly, we found that
the CB1/2 agonist displayed antiseizure efficacy against acute hypoxia-induced
seizures (automatisms, clonic and tonic-clonic seizures) and tonic-clonic
seizures evoked by PTZ. Anticonvulsant effects were seen in P10 animals but not
P20 animals. SIGNIFICANCE: Early life seizures represent a significant cause of
morbidity, with 30-40% of infants and children with epilepsy failing to achieve
seizure remission with current pharmacotherapy. Identification of new therapies
for neonatal/infantile epilepsy syndromes is thus of high priority. These data
indicate that the anticonvulsant action of the CB system is specific to CB1
receptor activation during early development and provide justification for
further examination of CB1 receptor agonists as novel antiepileptic drugs
targeting epilepsy in infants and children.
PMID- 28691159
TI - Establishment of a hepatocyte line for studying biosynthesis of long-chain
polyunsaturated fatty acids from a marine teleost, the white-spotted spinefoot
Siganus canaliculatus.
AB - A hepatocyte line was established from the liver of white-spotted spinefoot
Siganus canaliculatus to study the biosynthesis of long-chain polyunsaturated
fatty acids (LC-PUFA). The cells from the line, designated S. canaliculatus
hepatocyte line (SCHL), grew and multiplied well in Dulbecco's modified Eagle's
medium (DMEM)-F12 medium supplemented with 20 mM 4-(2-hydroxyethyl) piperazine-1
ethanesulphonic acid (HEPES), 10% foetal bovine serum (FBS) and 0.5% rainbow
trout Oncorhychus mykiss serum at 28 degrees C, showing an epithelial-like
morphology and the normal chromosome number of 48 (2n) and have been subcultured
for over 60 passages. The identity of the hepatocytes was confirmed by periodic
acid Schiff (PAS) staining. The mRNA expression of all genes encoding the key
enzymes for LC-PUFA biosynthesis including two desaturases (Delta4 Fad and Delta6
Delta5 Fad) and two elongases (Elovl4 and Elovl5), were detected in all cells
from passages 5 to 60 and their expression levels became stable after passage 35
and showed responses to various PUFA incubation. This is similar to the situation
determined in the liver of S. canaliculatus that were fed diets containing
different fatty acids. These results indicated that SCHL was successfully
established and can provide an in vitro tool to investigate lipid metabolism and
regulatory mechanisms of LC-PUFA biosynthesis in teleosts, especially marine
species.
PMID- 28691160
TI - The CYCLOIDEA-RADIALIS module regulates petal shape and pigmentation, leading to
bilateral corolla symmetry in Torenia fournieri (Linderniaceae).
AB - The diverse pigmentation patterns of flower corollas probably result from
pollinator-mediated selection. Previous studies demonstrated that R2R3-MYB
factors may have been recruited in the regulation of corolla pigmentation.
However, how R2R3-MYBs became so diverse in their regulation of different
pigmentation patterns remains unclear. Here, we studied a Lamiales species,
Torenia fournieri, which has elaborate zygomorphic flowers with dorsal-ventral
asymmetries in corolla pigmentation. We found recent gene duplication events in
CYCLOIDEA-like (CYC-like) and RADIALIS-like (RAD-like) genes, and functionally
analyzed three dorsal-specific expression factors: TfCYC1, TfCYC2, and TfRAD1. We
found that the CYC-RAD module coordinates petal shape and corolla pigmentation,
as ectopic expression of TfCYC2 or TfRAD1 disrupted the asymmetric corolla
pigmentation pattern and produced strongly dorsalized flowers. Dorsal petal
identity was lost when TfCYC2 was down-regulated or when TfRAD1 was knocked out.
In T. fournieri, the diversified CYC and RAD genes have evolved regulatory loops,
and TfCYC2 binds directly to the regulatory regions of an R2R3-MYB factor gene,
TfMYB1, which might lead to its asymmetric expression and ultimately establish
the asymmetric pigmentation pattern. These findings support the existence of a
regulatory module that integrates dorsal-ventral patterning and asymmetric
corolla pigmentation in T. fournieri.
PMID- 28691161
TI - Eruptive vellus hair cysts of the vulva.
PMID- 28691162
TI - Systemic lupus erythematosus, following prodromal idiopathic thrombocytopenic
purpura, presenting with skin lesions resembling malignant atrophic papulosis.
AB - Systemic lupus erythematosus (SLE) is an autoimmune disease. Its incidence in the
UK is approximately 1 per 10 000. Cutaneous involvement, encompassing acute,
subacute and chronic disease, occurs in over two-thirds of cases, and can often
be the first clue to diagnosis. We describe a highly unusual case of SLE
occurring after prodromal idiopathic thrombocytopenic purpura (ITP) and
presenting with skin lesions more typical of malignant atrophic papulosis, a rare
and often fatal vasculopathy. Such a combination of rare features emphasizes the
potential for complexity in this multisystem disease.
PMID- 28691163
TI - Clarithromycin, rifampicin and fusidic acid triple combination therapy for
chronic folliculocentric pustulosis of the scalp.
PMID- 28691164
TI - Pick's disease with neuronal four-repeat tau accumulation in the basal ganglia,
brain stem nuclei and cerebellum.
AB - It is very rare that cases of Pick's disease, a representative three-repeat (3R)
tauopathy, also have significant four-repeat (4R) tau accumulation. Here, we
report a Pick's disease case that clinically showed behavioral variant
frontotemporal dementia without motor disturbance during the course, and
pathologically had 3R tau-positive Pick bodies as well as numerous 4R tau
positive neuronal cytoplasmic inclusions (NCIs). Abundant 3R tau-positive 4R tau
negative spherical or horseshoe-shaped Pick bodies were found in the
frontotemporal cortex, limbic region, striatum and pontine nucleus. On the other
hand, many 4R tau-positive, 3R tau-negative, Gallyas-negative dot-, rod- or
intertwined skein-like NCIs were found mainly in the subthalamic nucleus, pontine
nucleus, inferior olivary nucleus and cerebellar dentate nucleus. Tufted
astrocytes, astrocytic plaques, argyrophilic grains or globular glial inclusions
were absent. Double-labeling immunofluorescence demonstrated that 3R tau was
hardly accumulated in 4R tau-positive inclusions. On tau immunoblotting, while 60
and 64 kDa bands were demonstrated in the frontal cortex, 60, 64 and 68 kDa
bands, as well as the 33 kDa tau fragments that are reported to be characteristic
of progressive supranuclear palsy brains, were found in the basal ganglia and
cerebellum. No mutation was identified in the tau gene. The present case suggests
that, although probably rare, some Pick's disease cases have non-negligible 4R
tau pathology in the subcortical nuclei, and that such 4R tau pathology can
affect the evaluation of the distribution of AT8-positive tau pathology in Pick's
disease cases.
PMID- 28691166
TI - Unilateral linear basaloid follicular hamartoma: Its diagnosis and successful
treatment with surgical excision and adjuvant dermabrasion.
PMID- 28691165
TI - Stabilization of protein structure through pi-pi interaction in the second
coordination sphere of pseudoazurin.
AB - Noncovalent, weak interactions in the second coordination sphere of the copper
active site of Pseudoazurin (PAz) from Achromobacter cycloclastes were examined
using a series of Met16X variants. In this study, the differences in protein
stability due to the changes in the nature of the 16th amino acid (Met, Phe, Val,
Ile) were investigated by electrospray ionization mass spectrometry (ESI-MS) and
far-UV circular dichroism (CD) as a result of acid denaturation. The percentage
of native states (folded holo forms) of Met16Phe variants was estimated to be 75%
at pH 2.9 although the wild-type (WT), Met16Val and Met16Ile PAz, became
completely unfolded. The high stability under acidic conditions is correlated
with the result of the active site being stabilized by the aromatic substitution
of the Met16 residue. The pi-pi interaction in the second coordination sphere
makes a significant contribution to the stability of active site and the protein
matrix.
PMID- 28691167
TI - Exploring the Link between Visual Perception, Visual-Motor Integration, and
Reading in Normal Developing and Impaired Children using DTVP-2.
AB - Reading is known to be primarily a linguistic task. However, to successfully
decode written words, children also need to develop good visual-perception
skills. Furthermore, motor skills are implicated in letter recognition and
reading acquisition. Three studies have been designed to determine the link
between reading, visual perception, and visual-motor integration using the
Developmental Test of Visual Perception version 2 (DTVP-2). Study 1 tests how
visual perception and visual-motor integration in kindergarten predict reading
outcomes in Grade 1, in typical developing children. Study 2 is aimed at finding
out if these skills can be seen as clinical markers in dyslexic children (DD).
Study 3 determines if visual-motor integration and motor-reduced visual
perception can distinguish DD children according to whether they exhibit or not
developmental coordination disorder (DCD). Results showed that phonological
awareness and visual-motor integration predicted reading outcomes one year later.
DTVP-2 demonstrated similarities and differences in visual-motor integration and
motor-reduced visual perception between children with DD, DCD, and both of these
deficits. DTVP-2 is a suitable tool to investigate links between visual
perception, visual-motor integration and reading, and to differentiate cognitive
profiles of children with developmental disabilities (i.e. DD, DCD, and comorbid
children). Copyright (c) 2017 John Wiley & Sons, Ltd.
PMID- 28691168
TI - Phenotyping of lumbosacral stenosis in Labrador retrievers using computed
tomography.
AB - Deep phenotyping tools for characterizing preclinical morphological conditions
are important for supporting genetic research studies. Objectives of this
retrospective, cross-sectional, methods comparison study were to describe and
compare qualitative and quantitative deep phenotypic characteristics of
lumbosacral stenosis in Labrador retrievers using computed tomography (CT).
Lumbosacral CT scans and medical records were retrieved from data archives at
three veterinary hospitals. Using previously published qualitative CT diagnostic
criteria, a board-certified veterinary radiologist assigned dogs as either
lumbosacral stenosis positive or lumbosacral stenosis negative at six vertebral
locations. A second observer independently measured vertebral canal area,
vertebral fat area, and vertebral body area; and calculated ratios of vertebral
canal area/vertebral body area and vertebral fat area/vertebral body area (fat
area ratio) at all six locations. Twenty-five dogs were sampled (lumbosacral
stenosis negative, 11 dogs; lumbosacral stenosis positive, 14 dogs). Of the six
locations, cranial L6 was the most affected by lumbosacral stenosis (33%). Five
of six dogs (83%) with clinical signs of lumbosacral pain were lumbosacral
stenosis positive at two or more levels. All four quantitative variables were
significantly smaller at the cranial aspects of the L6 and L7 vertebral foramina
than at the caudal aspects (P < 0.0001). Fat area ratio was a significant
predictor of lumbosacral stenosis positive status at all six locations with
cranial L6 having the greatest predictive value (R2 = 0.43) and range of
predictive probability (25-90%). Findings from the current study supported the
use of CT as a deep phenotyping tool for future research studies of lumbosacral
stenosis in Labrador retrievers.
PMID- 28691170
TI - The Body Mass Index of Adolescents Attending Seventh-Day Adventist Schools in
Australia: 2001-2012.
AB - BACKGROUND: We examined the body mass index (BMI) of students attending Seventh
day Adventist (Adventist) schools in Australia in 2001 and 2012. METHODS: A total
of 3069 students attending Adventist schools in Australia responded to a health
and lifestyle survey in 2001 (N = 1335) and 2012 (N = 1734). The survey captured
self-reported height and weight, demographics (age, sex, year level, religion),
and select health behaviors. RESULTS: Compared with national norms, lower rates
of overweight and obesity were observed in the study cohort, but higher rates of
underweight. There was no change in the mean BMI of the students attending
Adventist schools in Australia from 2001 to 2012. Regression analyses indicated
that a lower BMI was associated with age, sex, more regularly eating breakfast,
consuming less soft drink, and having a regular exercise program. The students
reported a high consumption of fruits, vegetables, and whole grains compared with
Australian national norms, and 29% claimed to be vegetarian. CONCLUSIONS:
Students attending Adventist schools appear to have a lower prevalence of
overweight and obesity than the secular population, but a higher prevalence of
underweight. The mechanisms through which Adventist schools may influence
student's BMI warrants further investigation.
PMID- 28691169
TI - Academic Performance in Primary School Children With Common Emotional and
Behavioral Problems.
AB - BACKGROUND: Many emotional and behavioral problems first emerge in primary school
and are the forerunners of mental health problems occurring in adolescence.
However, the extent that these problems may be associated with academic failure
has been explored less. We aimed to quantify the association between emotional
and behavioral problems with academic performance. METHODS: A stratified random
sample of 8- to 9-year-olds (N = 1239) were recruited from schools in Australia.
Data linkage was performed with a national assessment of academic performance to
assess reading and numeracy. Parent report assessed emotional and behavioral
problems with students dichotomized into "borderline/abnormal" and "normal"
categories. RESULTS: One in 5 grade 3 students fell in the "borderline/abnormal"
category. Boys with total difficulties (beta = -47.8, 95% CI: -62.8 to -32.8),
conduct problems, and peer problems scored lower on reading. Numeracy scores were
lower in boys with total difficulties (beta = -37.7, 95% CI: -53.9 to -21.5) and
emotional symptoms. Children with hyperactivity/inattention scored lower in
numeracy. Girls with peer problems scored lower in numeracy. CONCLUSIONS: Boys
with emotional and behavioral problems in mid-primary school were 12 months
behind their peers. Children with emotional and behavioral problems are at high
risk for academic failure, and this risk is evident in mid-primary school.
PMID- 28691171
TI - Utilization of Mental Health Services in School-Based Health Centers.
AB - BACKGROUND: We summarize utilization patterns for mental health services in
school-based health centers. METHODS: Administrative data on school-based health
center visits in New Haven, Connecticut were examined for the 2007-2009 school
years. Relative frequencies of mental health visits by age were calculated as a
percentage of all visits and were stratified by sex, ethnicity/race, and
insurance status. RESULTS: Mental health visits accounted for the highest
proportion of visits (31.8%). The proportion of mental health visits was highest
at 8 years (42.8%) and at 13 years (39.0%). The proportion of mental health
visits among boys (38.4%) was higher than among girls (26.7%). Hispanic students
had a lower proportion of mental health visits than black students (23.5% vs
35.8%) in all but 2 age groups. Students in the white/other ethnicity category
had higher proportions of mental health visits than Hispanic and black students
between ages 12 and 15. Students with no health insurance (22.5%) had lower
proportions of mental health visits than students covered by Medicaid (34.3%) or
private insurance (33.9%). The percentage of mental health visits by students
with private insurance was highest (37.2%-49%) in the 13-15 age range.
CONCLUSIONS: Usage patterns for mental health issues show pronounced, nonrandom
variation relative to age and other demographic characteristics especially with 8
year-old boys.
PMID- 28691172
TI - Physical Education Increases Daily Moderate to Vigorous Physical Activity and
Reduces Sedentary Time.
AB - BACKGROUND: Physical activity (PA) is important to mental and physical health.
Physical education (PE) lessons have the potential to increase daily moderate to
vigorous PA (MVPA) and reduce sedentary time (SED). We measured MVPA and SED in
primary school PE, determined the contribution of PE to daily MVPA and SED, and
compared PA on days with and without PE. METHODS: PA was measured in 504 first
(ages 7-9) and second (ages 10-12) school level children for 1 school week, with
inclusion criteria of at least 10 hours of valid data. Linear mixed methods were
used for data analysis. RESULTS: In PE, students spent 28.6 +/- 16.5% in MVPA and
29.3 +/- 19.8% in SED. Each additional MVPA minute in PE was associated with 1.4
more daily MVPA minutes. On days with PE, students had 12.8 (95% CI 10.5; 15.0)
minutes more MVPA and 9.7 (95% CI 16.3; 3.1) minutes less SED compared with days
without PE. CONCLUSIONS: Although MVPA in PE was relatively low and SED high, PE
significantly increased daily MVPA and reduced SED, confirming the important role
of PE in supporting the healthy development of children.
PMID- 28691173
TI - Successes and Challenges in School Meal Reform: Qualitative Insights From Food
Service Directors.
AB - BACKGROUND: The Healthy, Hunger-Free Kids Act of 2010 (HHFKA) directed the US
Department of Agriculture (USDA) to revise school meal standards to increase
healthy food offerings. A critical stakeholder in the implementation of standards
is Food Service Directors (FSDs). We sought to examine FSDs' perspectives on
revised school meal standards to gain insight into successful implementation
strategies. METHODS: Semistructured interviews were conducted with FSDs (N = 9)
from high schools that had achieved HealthierUS Schools Challenge: Smarter
Lunchrooms (HUSSC: SL) status. Qualitative interview data were team coded in
Atlas.ti v7 and analyzed with principles of constant comparative analysis.
RESULTS: FSDs reported overall positive perceptions of the revised school meal
standards and its potential impacts, as well as improved fruit and vegetable
consumption, despite initial challenges with plate waste, procurement of whole
grain-rich products, and fast paced sodium targets. Implementation was described
as complex, ongoing processes; with time and in-service trainings, student
acceptance to these changes improved. CONCLUSIONS: These findings are directly
relevant to future reauthorization of the Child Nutrition Act and to revisions to
the implementation time line for the federal school meal standards related to
sodium, whole grains, and flavored milk. Insights into FSDs' strategies suggest
that more time and targeted technical assistance at federal, state, and local
levels is warranted.
PMID- 28691174
TI - The Association of School Climate, Depression Literacy, and Mental Health Stigma
Among High School Students.
AB - BACKGROUND: Although school climate is linked with youth educational,
socioemotional, behavioral, and health outcomes, there has been limited research
on the association between school climate and mental health education efforts. We
explored whether school climate was associated with students' depression literacy
and mental health stigma beliefs. METHODS: Data were combined from 2 studies: the
Maryland Safe Supportive Schools Project and a randomized controlled trial of the
Adolescent Depression Awareness Program. Five high schools participated in both
studies, allowing examination of depression literacy and stigma measures from 500
9th and 10th graders. Multilevel models examined the relationship between school
level school climate characteristics and student-level depression literacy and
mental health stigma scores. RESULTS: Overall school climate was positively
associated with depression literacy (odds ratio [OR] = 2.78, p < .001) and
negatively associated with stigma (Est. = -3.822, p = .001). Subscales of
engagement (OR = 5.30, p < .001) and environment were positively associated with
depression literacy (OR = 2.01, p < .001) and negatively associated with stigma
(Est. = -6.610, p < .001), (Est. = -2.742, p < .001). CONCLUSIONS: Positive
school climate was associated with greater odds of depression literacy and
endorsement of fewer stigmatizing beliefs among students. Our findings raise
awareness regarding aspects of the school environment that may facilitate or
inhibit students' recognition of depression and subsequent treatment-seeking.
PMID- 28691175
TI - The Impact of Multiple Strategies to Encourage Fruit and Vegetable Consumption
During School Lunch.
AB - BACKGROUND: Hennepin County partnered with schools to implement lunchroom
strategies to encourage fruit and vegetable consumption. An in-depth evaluation
measured changes in consumption following implementation of encouragement
strategies including slicing apples and attractive labels. METHODS: A pre-post
prospective evaluation measured changes in average fruit and vegetable
consumption at 2 elementary schools. The plate waste method was used to weigh
individual waste. To measure consumption, 373 students were matched pre/post.
Additional measures included change in fruit and vegetable selection, change in
whole servings consumed and apple consumption. RESULTS: Average fruit consumption
increased by 3.0 g (p = .09), average vegetable consumption increased by 1.1 g (p
= .27), neither significantly. The number of students selecting fruit
significantly increased (p = .02), while the number taking vegetables increased,
but not significantly (p = .28). The number of students consuming an entire
serving of fruit (p = .15) or vegetables (p = .45) both increased but not
significantly. Apple consumption more than doubled at one school. CONCLUSIONS:
Implementing lunchroom changes can increase the number of students selecting
fruit, and changes including slicing can increase consumption of apples.
Additional strategies are needed to increase vegetable selection and fruit and
vegetable consumption.
PMID- 28691176
TI - Attitudes, Norms, and the Effect of Social Connectedness on Adolescent Sexual
Risk Intention.
AB - BACKGROUND: Risky sexual behaviors put adolescents at increased risk of adverse
outcomes. Parents, school-based adults, and peers play important roles in
influencing these sex intentions. METHODS: This work explored the influence of
parent-child sex communication on adolescent attitudes, perceived norms, and
intentions to have sex, including the moderating role of social support from
school-based adults, in a sample of 21,731 adolescents in California. RESULTS:
Although increased parent-child sex communication was associated with intentions
to have sex, it also exhibited protective effects, increasing abstinence
attitudes among youth that led to decreased intention directly and via support
from school-based adults. CONCLUSIONS: Although many factors influencing sexual
behaviors are largely intrapersonal, these findings indicate the importance of an
ecological approach to reducing adolescent sexual risk behaviors through
engagement of parents and increased school connectedness.
PMID- 28691177
TI - Children With Type 1 Diabetes Mellitus: Self-Management Experiences in School.
AB - BACKGROUND: Children with type 1 diabetes mellitus (T1DM) need to perform self
management activities at school and in other environments. Learning about their
experiences at school is crucial to assist them in this challenging task.
METHODS: Qualitative interviews were conducted with children with T1DM, aged
between 7 and 12. A scenario was created and puppets were used during the
interviews to help the participating children to communicate about school, daily
routines, and experiences in diabetes management. Data were collected over a
period of 1 year and analyzed according to content analysis procedures. RESULTS:
Nineteen children, 13 boys and 6 girls, at the mean age of 9.8 +/- 1.8 years and
mean time since diagnosis of 3.3 years, participated in the study. Three themes
were identified: lack of information on T1DM, diabetes self-care at school, and
support received by the children. CONCLUSIONS: The study provides useful
information to understand the children's experiences in managing the disease at
school. The partnership between school staff, health teams, children with T1DM,
and their families need to be enhanced to promote appropriate strategies that
improve the management of diabetes in this setting.
PMID- 28691178
TI - Cancer risk among Holocaust survivors in Israel-A nationwide study.
AB - BACKGROUND: Holocaust survivors during World War II were exposed to various
factors that are associated with cancer risk. The objective of this study was to
determine whether Holocaust survivors had an increased risk for developing
cancer. METHODS: The study population included 152,622 survivors. The main
analysis was based on a comparison between individuals who were entitled to
compensation for suffering persecution during the war and individuals who were
denied such compensation. A complementary analysis compared survivors who were
born in countries governed by Nazi Germany with survivors born in nonoccupied
countries. A Cox proportional hazards model was used, with the time at risk of
cancer development starting on either January 1, 1960, or the date of immigration
to the date of cancer diagnosis or death or the date of last follow-up (December
31, 2006). RESULTS: Cancer was diagnosed in 22.2% of those who were granted
compensation versus 16% of those who were denied compensation (P < .0001).
Adjusting for birth cohort, sex, country of origin, and period of immigration,
both analyses revealed significant increased risks of developing cancer in those
who were exposed. For those who were granted versus denied compensation, the
hazard ratios were 1.06 (P < .001) for all sites, 1.12 (P = .07) for colorectal
cancer, and 1.37 (P = .008) for lung cancer. For those born in occupied countries
versus nonoccupied countries, the hazard ratios were 1.08 (P < .001), 1.08 (P =
.003), and 1.12 (P = .02), respectively. CONCLUSIONS: The current results, based
on a large cohort of Holocaust survivors who were exposed to a variety of severe
deprivations, add to the conflicting and sparse knowledge on this issue and
support the notion that this group has a small but consistent increase in cancer
development. Cancer 2017;123:3335-45. (c) 2017 American Cancer Society.
PMID- 28691179
TI - Microtubular Fuel Cell with Ultrahigh Power Output per Footprint.
AB - A novel realization of microtubular direct methanol fuel cells (uDMFC) with
ultrahigh power output is reported by using "rolled-up" nanotechnology. The
microtube (Pt-RuO2 -RUMT) is prepared by rolling up Ru2 O layers coated with
magnetron-sputtered Pt nanoparticles (cat-NPs). The uDMFC is fabricated by
embedding the tube in a fluidic cell. The footprint of per tube is as small as
1.5 * 10-4 cm2 . A power density of ~257 mW cm-2 is obtained, which is three
orders of magnitude higher than the present microsized DFMCs. Atomic layer
deposition technique is applied to alleviate the methanol crossover as well as
improve stability of the tube, sustaining electrolyte flow for days. A laminar
flow driven mechanism is proposed, and the kinetics of the fuel oxidation depends
on a linear-diffusion-controlled process. The electrocatalytic performance on
anode and cathode is studied by scanning both sides of the tube wall as an ex
situ working electrode, respectively. This prototype uDFMC is extremely
interesting for integration with micro- and nanoelectronics systems.
PMID- 28691180
TI - Examining the association between language, expository discourse and offending
behaviour: an investigation of direction, strength and independence.
AB - BACKGROUND: A high prevalence of Developmental Language Disorder (DLD) is
reported in the population of Young Offenders (YO). However, little is known
about the extent of the association between language and offending behaviour
relative to social disadvantage, education attendance and non-verbal intelligence
(IQ), and neither has this association been investigated with particular
reference to the expository discourse abilities of YOs on community orders in the
UK. AIMS: This study aimed to examine the direction and strength of the
association between language and offending behaviour by comparing the receptive
and expressive language and expository discourse abilities of male and female YOs
and non-offenders in the UK, relative to the confounds of social disadvantage,
years of education attended and non-verbal IQ. Examining expository discourse
provided a measure of the YOs. ability to verbally communicate complex
information; a communication ability that is fundamental to engaging effectively
in youth offending services and secondary education. METHODS: An opportunity
sample of 52 YOs was recruited from a youth offending service. The YO group was
matched on years of education, social disadvantage and non-verbal IQ to a purpose
selected comparison group of 25 non-offenders. All participants had English as
their first language and were not currently receiving any speech and language
intervention. Participants completed standardised measures of receptive and
expressive language and an expository discourse measure. The incidence of DLD was
identified and compared across offender group using scores from the language and
expository discourse measures and gender differences were also explored. Finally,
logistical regression analysis was used to test the association between language
performance and offending status relative to the confounds of social
disadvantage, education attendance and non-verbal IQ. OUTCOMES & RESULTS: A large
proportion of YOs scored below test norms for the language and expository
discourse measures, which indicated a high incidence of DLD that was much larger
than that displayed by the non-offenders. No differences were found on language
performance between male and female YOs. Logistic regression analyses found that
as language performance increased, the probability of being a non-offender
significantly increased. CONCLUSIONS & IMPLICATIONS: Participants were over 1 to
5 times more likely to be classified as a non-offender for every unit increase in
the language and expository discourse scores. The statistically significant
positive association found between language and offending behaviour relative to
other confounds, highlights the important role of language in understanding
offending behaviour. YOs displayed high incidences of DLD in their language and
expository discourse abilities despite having not received any speech and
language intervention prior to their involvement in this study. This has
implications for their effective engagement in education and in youth offending
and criminal justice services (CJS). Professionals in education, health and
social care and youth justice should be made aware of the language needs of both
YOs and children with emotional behavioural difficulties, and these language
needs should be identified and targeted as early as possible to enable them to be
effective communicators who can engage effectively in their provision.
PMID- 28691181
TI - Treatment of paediatric facial pyogenic granuloma with topical ingenol mebutate.
PMID- 28691182
TI - Heat shock protein 70 inhibitors suppress androgen receptor expression in LNCaP95
prostate cancer cells.
AB - Androgen deprivation therapy is initially effective for treating patients with
advanced prostate cancer; however, the prostate cancer gradually becomes
resistant to androgen deprivation therapy, which is termed castration-resistant
prostate cancer (CRPC). Androgen receptor splice variant 7 (AR-V7), one of the
causes of CRPC, is correlated with resistance to a new-generation AR antagonist
(enzalutamide) and poor prognosis. Heat shock protein 70 (Hsp70) inhibitor is
known to decrease the levels of full-length AR (AR-FL), but little is known about
its effects against CRPC cells expressing AR-V7. In this study, we investigated
the effect of the Hsp70 inhibitors quercetin and VER155008 in the prostate cancer
cell line LNCaP95 that expresses AR-V7, and explored the mechanism by which Hsp70
regulates AR-FL and AR-V7 expression. Quercetin and VER155008 decreased cell
proliferation, increased the proportion of apoptotic cells, and decreased the
protein levels of AR-FL and AR-V7. Furthermore, VER155008 decreased AR-FL and AR
V7 mRNA levels. Immunoprecipitation with Hsp70 antibody and mass spectrometry
identified Y-box binding protein 1 (YB-1) as one of the molecules regulating AR
FL and AR-V7 at the transcription level through interaction with Hsp70. VER155008
decreased the phosphorylation of YB-1 and its localization in the nucleus,
indicating that the involvement of Hsp70 in AR regulation might be mediated
through the activation and nuclear translocation of YB-1. Collectively, these
results suggest that Hsp70 inhibitors have potential anti-tumor activity against
CRPC by decreasing AR-FL and AR-V7 expression through YB-1 suppression.
PMID- 28691183
TI - Association between early life adversity and inflammation during infancy.
AB - Early life adversity is associated with adult elevations of inflammatory markers
such as circulating levels of C-reactive protein (CRP). Few studies have measured
inflammation or its association with psychosocial stress during infancy. Existing
evidence suggests that early adversity can embed itself into young children's
biology with implications for lifelong development. This study examined the
association between psychosocial stress and salivary CRP in infants. Early
adversity in the form of socioeconomic disadvantage and maternal psychosocial
stress were measured when infants were 17 months old. Resting state saliva
samples were collected to assess CRP (pg/ml) levels via enzyme immunoassay.
Results revealed that both socioeconomic disadvantage and maternal psychosocial
stress were independently associated with higher infant CRP levels. These results
raise questions about timing of exposure to adversity, and about the potentially
lasting effects on inflammatory processes when such exposure occurs early in
development.
PMID- 28691184
TI - Risk Factors for Post-treatment Complex Regional Pain Syndrome (CRPS): An
Analysis of 647 Cases of CRPS from the Danish Patient Compensation Association.
AB - OBJECTIVES: Complex regional pain syndrome is a challenging condition that
includes a broad spectrum of sensory, autonomic, and motor features predominantly
in extremities recovering from a trauma. Few large-scale studies have addressed
occurrence of and factors associated with complex regional pain syndrome (CRPS)
following orthopedic treatment. The present study aimed to identify factors
associated with post-treatment development of CRPS. METHODS: Using the Danish
Patient Compensation Association's database, we identified 647 patients claiming
post-treatment CRPS between 1992 and 2015. Age, gender, initial diagnosis,
treatment, and amount of compensation were extracted. Multivariate logistic
regressions were performed to identify variables associated with approval of the
claim. For carpal tunnel syndrome (CTS) patients, we registered whether symptoms
were bilateral or unilateral and if neurophysiology prior to treatment was
pathologic. RESULTS: The following ratios were found: women:men was 4:1, primary
diagnosis to the upper limb:lower limb was 2.5:1, and surgical:nonsurgical
treatment was 3:1. Mean age was 47.5 +/- 13.7 years, and no intergender
difference was detected. Antebrachial fracture (23%) and CTS (9%) were the most
common primary conditions. Surgical treatment was associated with approval of the
claim (odds ratio 3.5, 95% confidence interval 2.3 to 5.3; P < 0.001). Half of
CTS patients had normal neurophysiology prior to surgery; among patients with
unilateral symptoms, 71.4% had normal neurophysiology. CONCLUSIONS: Female
gender, surgical treatment, and treatment to the upper limb were risk factors.
Elective surgery accounted for a large number of post-treatment CRPS patients. In
CTS patients developing CRPS, normal neurophysiological examination findings were
common, and it could be suspected that these patients were suffering from an pre
clinical stage of CRPS, not CTS.
PMID- 28691185
TI - Regulating clinical trials in India: the economics of ethics.
AB - The relationship between the ethical standards for the governance of clinical
trials and market forces can be complex and problematic. This article uses India
as a case study to explore this nexus. From the mid-2000s, India became a popular
destination for foreign-sponsored clinical trials. The Indian government had
sought to both attract clinical trials and ensure these would be run in line with
internationally accepted ethical norms. Reports of controversial medical
research, however, triggered debate about the robustness and suitability of
India's regulatory system. In response to civil society pressure and
interventions by the Supreme Court, the Indian government proposed additional
measures aimed at strengthening protections for clinical trial participants.
Whilst the reforms can be seen as a victory for human rights activists, they have
also been criticised as being overly burdensome for sponsors. Indeed, their
announcement prompted an exodus of clinical trials from India. Fearful of losing
business to 'rival' countries, the Indian government is revisiting some of its
proposals. The Indian example suggests that research ethics frameworks and
national policies for economic development are increasingly intertwined. Host
countries are in theory free to improve the lot of research participants, but
doing so may make them appear less attractive to foreign sponsors, who can simply
shift their activities to more industry-friendly jurisdictions. Although these
economic pressures are unlikely to lead to a regulatory 'race to the bottom',
they may limit host countries' ability to enact socially desirable reforms.
PMID- 28691186
TI - Peroral endoscopic myotomy as salvation technique post-Heller: International
experience.
AB - BACKGROUND: Treatment for achalasia has traditionally been Heller myotomy (HM).
Despite its excellent efficacy rate, a number of patients remain symptomatic post
procedure. Limited data exist as to the best management for recurrence of
symptoms post-HM. We present an international, multicenter experience evaluating
the efficacy and safety of post-HM peroral endoscopic myotomy (POEM). METHODS:
Patients who underwent POEM post-HM from 13 centers from January 2012 to January
2017 were included as part of a prospective registry. Technical success was
defined as successful completion of the myotomy. Clinical success was defined as
an Eckardt score of <=3 on 12-month follow up. Adverse events (AE) including
anesthesia-related, operative, and postoperative complications were recorded.
RESULTS: Fifty-one patients were included in the study (mean age 54.2, 47% male).
Technical success was achieved in 100% of patients. Clinical success on long-term
follow up was achieved in 48 patients (94%), with a mean change in Eckardt score
of 6.25. Seven patients (13%) had AE: six experienced periprocedural mucosal
defect treated endoscopically and two patients developed mediastinitis treated
conservatively. CONCLUSION: For patients with persistent symptoms after HM, POEM
is a safe salvation technique with good short-term efficacy. As a result of the
challenge associated with repeat HM, POEM might become the preferred technique in
this patient population. Further studies with longer follow up are needed.
PMID- 28691187
TI - Therapeutic experience with oral finasteride for androgenetic alopecia in female
to-male transgender patients.
AB - BACKGROUND: Androgenic treatment of female-to-male transgender patients may
result in androgenetic alopecia (AGA). Use of 5-alpha-reductase inhibitors are
useful as oral treatment of AA in men. There are no previous studies of the use
of finasteride in transgender men as treatment of AGA. AIM: To evaluate the
effectiveness and safety of an oral 5alpha-reductase inhibitor (finasteride) for
AA developed in transgender men. METHODS: This single-centre retrospective study
enrolled female-to-male transgender patients with a clinical diagnosis of AGA to
receive 1 mg of an oral type II 5alpha-reductase inhibitor for at least 12
months. RESULTS: In all, 10 patients were included in the study. All the patients
received a clinical diagnosis of male-pattern AGA, with 90% classified as stage
IV on the Norwood-Hamilton scale. Mean onset of AGA was 3.25 years after the
introduction of androgenic treatment, and 70% of the patients had a family
history of AGA. All the patients improved one grade on the Norwood-Hamilton scale
after a mean of 5.5 months (range 4-6 months) since the start of finasteride
treatment. Two patients stopped treatment for economic reasons and one stopped
due to dyspepsia. No sexual or other adverse effects were observed. Patients were
given periodic physical and analytical examinations by endocrinologists without
any significant finding. Mean follow-up of patients was 16.2 months. CONCLUSION:
AA in transgender men has a delayed onset, and is clinically and therapeutically
similar to the common male-pattern-AGA in cis-gender men.
PMID- 28691188
TI - Tranexamic Acid in Total Knee Arthroplasty: Mixed Treatment Comparisons and
Recursive Cumulative Meta-Analysis of Randomized, Controlled Trials and Cohort
Studies.
AB - Tranexamic acid (TXA) has been shown to be effective in patients with total knee
arthroplasty (TKA) in clinical studies with no consensus with regard to the most
appropriate route of administration. We conducted a network meta-analysis to
compare the evidence available on efficacy and safety of TXA in TKA. Electronic
databases were searched for randomized, clinical trials and cohort studies that
evaluated TXA in TKA. Publication bias, risk of bias and inconsistencies were
assessed. Direct and indirect comparisons were carried out for blood transfusion
rate and incidence of thrombotic complications. Sensitivity analyses and grading
of evidence were performed for key comparisons. A cumulative meta-analysis was
conducted for comparisons that had a minimum of 10 included studies. A total of
19 studies with 8916 participants were pooled for this network meta-analysis. No
inconsistencies and publication bias were observed. Low risk of bias was observed
for the majority of the included studies. When compared to placebo, the pooled
estimates for mixed treatment analyses favoured (in the order of higher ranking)
the combined pre-operative oral and topical TXA, intra-operative intravenous TXA
with topical TXA, pre-operative intravenous TXA, intra-operative and post
operative intravenous TXA, intra-operative intravenous bolus and topical TXA.
Additionally, combined intravenous and topical TXA performed better than topical
TXA alone. No significant changes were observed in the sensitivity analyses. No
significant differences were observed in the risk of thrombotic complications
between the interventions. TXA is efficacious and safe in patients with TKA. The
combined topical and intra-operative intravenous TXA may perform better.
PMID- 28691189
TI - Hydroxamic Acids as Chemoselective (ortho-Amino)arylation Reagents via
Sigmatropic Rearrangement.
AB - The use of readily available hydroxamic acids as reagents for the chemoselective
(ortho-amino)arylation of amides is described. This reaction proceeds under metal
free, mild conditions, displays a very broad scope, and constitutes a direct
approach for the metal-free attachment of aniline residues to carbonyl
derivatives.
PMID- 28691190
TI - Seabather's eruption caused by the thimble jellyfish (Linuche aquila) in the
Philippines.
PMID- 28691191
TI - Divergence of a Tandem Duplication of Manganese Superoxide Dismutase in Nosema
bombycis.
AB - Manganese superoxide dismutase (MnSOD) is a key enzyme in the protection of cells
from oxidative stress. A tandem duplication of the MnSOD gene (NbMnSOD1 and
NbMnSOD2) in the genome of Nosema bombycis, a parasite of the silkworm Bombyx
mori, was previously identified. Here, we compare the protein structures of
NbMnSOD1 and NbMnSOD2 and characterize these two proteins in terms of cellular
localization, timing of transcription, protein structure, and enzyme activity.
Despite a similarity in the primary sequence of NbMnSOD1 and NbMnSOD2, the latter
shows a remarkable degree of amino acid sequence difference on the protein's
surface and in the active site, where there is a substitution of a phenylalanine
for a histidine in NbMnSOD2. Immuno-electron microscopy demonstrates that
NbMnSOD1 is present in the cytosol of mature spores, whereas NbMnSOD2 is
localized on the polar tube and the spore wall. Immunofluorescence confirms the
localization of NbMnSOD2 on the polar tube of the germinated spore. Quantitative
measurement of gene expression (qRT-PCR) demonstrates production of both alleles
during the first day of infection followed by a dramatic decrease during the
second to fourth day of infection. From the fifth day onward, the two alleles
show a complementary pattern of expression. The qRT-PCR of the host manganese
superoxide dismutase (BmMnSOD) shows a notable increase in transcription upon
infection, leading to a three-fold spike by the first day of infection, followed
by a decrease in transcription. Measurement of overall MnSOD activity shows a
similar peak at day 1 followed by a decrease to a constant rate of enzyme
activity. The differences in cellular localization and pattern of gene expression
of NbMnSOD2 compared to NbMnSOD1, as well as the differences in protein structure
seen for NbMnSOD2 compared to other microsporidial MnSODs, strongly suggest a
unique, recently evolved role for NbMnSOD2.
PMID- 28691192
TI - Bilirubin coating attenuates the inflammatory response to everolimus-coated
stents.
AB - The aim of this study was to evaluate the effects of bilirubin- and/or everolimus
(EVL)-coated stents to prevent arterial neointimal hyperplasia and inflammation
in vitro and in vivo. The stents were prepared by spray coating bare metal stents
(BMS) with bilirubin and/or EVL. Study groups were divided into (1) BMS, (2)
bilirubin-coated stents (BES), (3) commercialized stents (SynergyTM; EES), and
(4) bilirubin/EVL-coated stents (B-EES). The coating thickness and drug release
rates were comparable to previous reports (i.e., <4 um thickness and 50% drug
release in 7 days). Smooth muscle cell migration was inhibited in both EVL
containing groups (20.5 +/- 3.80% in EES and 18.4 +/- 2.55% in B-EES) compared to
the non-EVL-containing groups (78.0 +/- 6.41% in BMS and 76.1 +/- 4.88% in BES)
(n = 10, p < 0.05). Stents were randomly implanted to 40 coronary arteries in 20
pigs and subjected to various analyses after 4 weeks of implantation. As results,
the inflammation score was dramatically increased in the EES group (2.1 +/- 0.42)
compared to that of the other groups (1.5 +/- 0.55, 1.3 +/- 0.23, and 1.5 +/-
0.27 for BMS, BES, and B-EES, respectively, n = 10, p < 0.05). Immunofluorescence
analysis revealed that inflammation was prevented in the bilirubin-containing
groups (BES and B-EES). However, the percent area of restenosis was decreased in
the EVL-containing groups (20.5 +/- 4.11% for EES and 18.4 +/- 3.61% for B-EES)
compared to the non-EVL-containing groups (32.3 +/- 6.41% for BMS and 29.6 +/-
5.95% for BES, n = 10, p < 0.05). The percent areas of restenosis determined by
histopathology, optical coherence tomography, and micro-computed tomography were
consistent. In addition, the stent was barely covered in the EES and B-EES groups
at 4 weeks postimplantation. These dual drug-coated stents may be especially
beneficial to patients who have an increased risk of inflammation. These stents
have great potential for use in cardiovascular applications. (c) 2017 Wiley
Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1486-1495,
2018.
PMID- 28691193
TI - Fluralaner as a single dose oral treatment for Caparinia tripilis in a pygmy
African hedgehog.
AB - BACKGROUND: African pygmy hedgehogs (Atelerix albiventris) are popular pets
belonging to the Erinaceidae family of spined mammals. Amongst the most common
skin diseases occurring in this species is infestation caused by the mite
Caparinia spp. Due to their skin anatomy and spiny coat, detection of skin
lesions in these hedgehogs can be difficult. This may result in delays in seeking
medical care, which may lead to secondary bacterial infection and self-inflicted
trauma. Multiple therapies have been used in the treatment of this skin condition
including ivermectin, amitraz, fipronil and selamectin. A drug which could be
administered as a single oral dose would be advantageous to these pets and their
owners. OBJECTIVE: To evaluate the effect of a single oral dose (15 mg/kg) of
fluralaner on Caparinia tripilis infestation in the African pygmy hedgehog.
ANIMALS: A 10-month-old African pygmy hedgehog weighing 184 g. METHODS: Response
to treatment was monitored by dermatological examination and superficial skin
scrapings repeated at 7, 14, 21, 30, 60, 90 and 120 days following fluralaner
administration. RESULTS: On Day 7 after treatment, adult mites were observed
exhibiting normal movement. On Day 14, only dead mites were observed. No life
stages of the mites were found after Day 21. CONCLUSION AND CLINICAL IMPORTANCE:
A single oral dose at 15 mg/kg of fluralaner was effective within 21 days after
treatment for capariniasis in this case. Further studies are required to evaluate
the drug's safety and toxicology in hedgehogs, and to confirm efficacy.
PMID- 28691194
TI - Acute localised exanthematous pustulosis secondary to pembrolizumab.
PMID- 28691195
TI - Definitions of intradialytic hypotension.
AB - Intradialytic hypotension (IDH) is a common and often distressful complication of
hemodialysis. However, despite its clinical significance, there is no consensus,
evidence-based medical definition for the condition. Over the years, numerous
definitions have been implemented in both the clinical and research settings.
Definition inconsistencies have hindered data synthesis and the development of
evidence-based guidelines for the prevention and treatment of IDH, as well as
prevented accurate estimation of the population burden of IDH and patient risk
assessment. Most existing IDH definitions are comprised of one or more of the
following components: (1) intradialytic BP criteria (requisite BP declines or
minimum BP thresholds), (2) the provision of interventions aimed at restoring
effective arterial volume, and/or (3) patient-reported symptoms. Remarkably,
there are insufficient data to inform IDH definition construction, and it remains
unknown if a single, universal definition can adequately capture the condition
across patient subgroups, and in clinical and research settings.
PMID- 28691196
TI - The comprehensibility of pantomimes produced by people with aphasia.
AB - BACKGROUND: People with aphasia (PWA) use pantomime, gesture in absence of
speech, differently from non-brain-damaged people (NBDP). AIMS: To evaluate
through an exploratory study the comprehensibility of PWA's pantomimes and to
find out whether they can compensate for information PWA are unable to convey in
speech. METHODS & PROCEDURES: A total of 273 naive observers participated in one
of two judgement tasks: forced-choice and open-ended questions. These were used
to determine the comprehensibility of pantomimes produced to depict objects by
PWA as compared with NBDP. Furthermore, we compared the information conveyed in
pantomime with the information in speech. We looked into factors influencing
pantomime's comprehensibility: individual factors, manner of depiction and
information needed to be depicted. OUTCOME & RESULTS: Although comprehensibility
scores for PWA's pantomimes were lower than for those produced by NBDP, all PWA
were able to convey information in pantomime that they could not convey in
speech. Comprehensibility of pantomimes was predicted by apraxia. The inability
to use the right hand related to slightly lower comprehensibility scores. Objects
for which individuals depicted its use were best understood. CONCLUSION &
IMPLICATIONS: Our findings highlight the potential benefit of pantomime for
clinical practice. Pantomimes, even though sometimes impaired, can convey
information that PWA cannot convey in speech. Clinical implications are
discussed.
PMID- 28691197
TI - Loss of Dcc in the spinal cord is sufficient to cause a deficit in lateralized
motor control and the switch to a hopping gait.
AB - BACKGROUND: Humans with heterozygous mutations in the axon guidance receptor DCC
display congenital mirror movements (MMs), which are involuntary movements of
body parts, such as fingers, on one side of the body that mirror voluntary
movement of the opposite side. In mice, the homozygous Dcckanga mutant allele
causes synchronous MM-like hindlimb movements during locomotion, resulting in
hopping. In both human and mice, the neuroanatomical defect responsible for the
deficit in lateralized motor control remains to be elucidated. RESULTS: Using the
HoxB8-Cre line to specifically remove Dcc from the spinal cord, we found
misrouting of commissural axons during their migration toward the floor plate,
resulting in fewer axons crossing the midline. These mice also have a hopping
gait, indicating that spinal cord guidance defects alone are sufficient to cause
hopping. CONCLUSIONS: Dcc plays a role in the development of local spinal
networks to ensure proper lateralization of motor control during locomotion.
Local spinal cord defects following loss of Dcc cause a hopping gait in mice and
may contribute to MM in humans. Developmental Dynamics 247:620-629, 2018. (c)
2017 Wiley Periodicals, Inc.
PMID- 28691199
TI - Erratum.
PMID- 28691198
TI - Dyadic Coping in Couple Therapy Process: An Exploratory Study.
AB - This study aimed at moving beyond previous research on couple therapy efficacy by
examining moment-by-moment proximal couple and therapist interactions as well as
final treatment outcomes and their reciprocal association. Seven hundred four
episodes of dyadic coping within 56 early therapy sessions, taken from 28 married
couples in treatment, were intensively analyzed and processed using a mixed
methods software (T-LAB). Results showed that negative dyadic coping was self
perpetuating, and therapists tended to passively observe the negative couple
interaction; on the contrary, positive dyadic coping appeared to require a
therapist's intervention to be maintained, and successful interventions mainly
included information gathering as well as interpreting. Couples who dropped out
of treatment were not actively engaged from the outset of therapy, and they used
more negative dyadic coping, whereas couples who successfully completed treatment
showed more positive dyadic coping very early in therapy. Results highlight the
role of therapist action and control as critical to establishing rapport and
credibility in couple therapy and suggest that dyadic coping patterns early in
therapy may contribute to variable treatment response.
PMID- 28691200
TI - The Chemistry of 1-Acylphosphirane Complexes: A Phosphorus Analogue of the Cloke
Wilson Rearrangement.
AB - The stabilization of a phosphirane ring by complexation to tungsten pentacarbonyl
allows the emergence of the Cloke-Wilson rearrangement in 1-acylphosphirane
complexes around 130 degrees C. Contrary to the cyclopropane case, this
transformation of the 1-acylphosphirane to the 1,3-oxaphosphol-3-ene complexes is
reversible. It is favored by a 2-phenyl, and even a 2-vinyl substitution. The 1,3
oxaphosphol-3-ene complexes are trapped by conjugated dienes.
PMID- 28691201
TI - Combined myocardial deformation to predict cardiac resynchronization therapy
response in nonischemic cardiomyopathy.
AB - BACKGROUND: 20-30% of patients do not benefit from cardiac resynchronization
therapy (CRT) when the established selection criteria were applied. We
hypothesized that a combined assessment of mechanical dyssynchrony, myocardial
deformation, and diastolic function would identify patients who would benefit
most from CRT. METHOD: In 36 CRT patients, clinical evaluation and
echocardiography were performed before and after CRT. Patients were classified
into three subgroups according to their amount of response: echocardiographic
responders, clinical responders, and nonresponders. Radial dyssynchrony and left
ventricular (LV) global longitudinal, radial, and circumferential peak strain was
assessed by speckle-tracking image. Diastolic function was quantified by
conventional echocardiography. RESULT: In addition to left bundle branch block,
nonspecific intraventricular conduction disturbance with intraventricular
dyssynchrony could also improve LV remodeling. Echocardiographic responders had
better global longitudinal strain, global circumferential peak strain, and global
radial strain at baseline which significantly increased at 12-month follow-up. An
improvement in estimates of LV filling pressure and a decrease in mitral
regurgitation and left atrial dimensions were observed only in echocardiographic
responders to CRT. Patients with clinical but without echocardiographic response
showed a significant improvement in atrioventricular (AV) synchrony and a
nonsignificant improvement in other parameters. The nonresponder group did not
improve the AV and intraventricular dyssynchrony. CRT could not improve
restrictive filling pattern with normal filling time. Overall, those patients
with AV and intraventricular dyssynchrony and those with best contractile
function and short diastolic filling time of restrictive filling pattern at
baseline demonstrated the greatest benefit from CRT. CONCLUSIONS: Mechanical
dyssynchrony, contractile function, and filling pattern are important
determinants of the benefits in CRT.
PMID- 28691202
TI - Methadone versus Fentanyl in Patients with Radiation-Induced Nociceptive Pain
with Head and Neck Cancer: A Randomized Controlled Noninferiority Trial.
AB - BACKGROUND: Pain is still a burden for many patients with cancer. A recent trial
showed the superiority of methadone over fentanyl in neuropathic pain, and we
expect that this finding could influence the number of patients treated with
methadone. METHODS: We performed a randomized controlled noninferiority trial in
patients with nociceptive pain. Eighty-two strong-opioid-naive patients with head
and neck cancer with substantial pain (pain numeric rating scale [NRS] score >=
4) due to radiation therapy were included. Forty-two patients were treated with
methadone, and 40 with fentanyl. Patients were evaluated at 1, 3, and 5 weeks.
The primary outcomes were reduction in average pain and clinical success (50%
pain decrease). We set the predefined noninferiority margin at 1 on the NRS and
10% clinical success. Secondary outcomes were pain interference, global perceived
effect (GPE), side effects, and opioid escalation index. RESULTS: Noninferiority
was shown for decrease in NRS for maximum and mean pain scores at 1 and 3 weeks.
Noninferiority was shown for clinical success at 1 week only. The opioid
escalation index was lower in the methadone group at 3 and 5 weeks as compared to
fentanyl (1.44 vs. 1.99, P = 0.004; and 1.50 vs. 2.32, P = 0.013). The pain
interference in the methadone group was significantly decreased at 3 weeks only.
GPE and side effects were not different. CONCLUSION: This is the first study to
show noninferiority of methadone compared to fentanyl at 1 and 3 weeks in the
treatment of radiation-induced nociceptive pain in patients with head and neck
cancer.
PMID- 28691203
TI - Previously undiagnosed risk factors and medication nonadherence are prevalent in
young adults with first-ever stroke.
AB - PURPOSE: The incidence of stroke and prevalence of traditional vascular risk
factors (VRFs) in young adults (age < 55 y) are both increasing. Young patients
tend to be unaware of their VRFs and to have lower medication adherence. We
examined how age affects the prevalence of previously undiagnosed VRFs and the
extent of medication nonadherence among stroke patients. METHODS: Using Taiwan's
National Health Insurance Research Database, we identified consecutive adult
patients with first-ever stroke between 2000 and 2013. Diagnosis of hypertension,
diabetes, and hyperlipidemia was ascertained using validated methods. We
investigated (1) the proportion of patients who had undiagnosed VRFs within 3
years before stroke and (2) the proportion of nonadherence to medications among
patients who had a previously diagnosed VRF. RESULTS: Among stroke patients with
hypertension (n = 9722), diabetes (n = 4751), and hyperlipidemia (n = 4486),
24.9%, 20.8%, and 55.0%, respectively, had not been diagnosed before stroke,
whereas 56.0%, 66.7%, and 32.5%, respectively, had been diagnosed at least 1 year
before stroke. The proportions of medication nonadherence were 71.5%, 64.3%, and
88.4% in patients with previously diagnosed hypertension, diabetes, and
hyperlipidemia, respectively. In multivariate analysis, younger age was
independently associated with undiagnosed hypertension before stroke as well as
medication nonadherence in patients with previously diagnosed hypertension or
diabetes. CONCLUSIONS: Previously undiagnosed hypertension and nonadherence to
treatment of hypertension and diabetes were more prevalent in young adult
patients with first-ever stroke in Taiwan. Interventions targeting young people
to promote early detection and adequate control of VRFs should be encouraged.
PMID- 28691204
TI - Mortality with brainstem seizures from focal 4-aminopyridine-induced recurrent
hippocampal seizures.
AB - OBJECTIVE: Sudden unexplained death in epilepsy is the leading cause of death in
young adult epilepsy patients, typically occurring during the early postictal
period, presumably resulting from brainstem and cardiorespiratory dysfunction. We
hypothesized that ictal discharges in the brainstem disrupt the cardiorespiratory
network, causing mortality. To study this hypothesis, we chose an animal model
comprising focal unilateral hippocampal injection of 4-aminopyridine (4-AP),
which produced focal recurrent hippocampal seizures with secondary generalization
in awake, behaving rats. METHODS: We studied ictal and interictal intracranial
electrographic activity (iEEG) in 23 rats implanted with a custom electrode array
into the hippocampus, the contralateral cortex, and brainstem. The hippocampal
electrodes contained a cannula to administer the potassium channel blocker and
convulsant (4-AP). iEEG was recorded continuously before, during, and after
seizures induced by 4-AP infusion into the hippocampus. RESULTS: The control
group (n = 5) was monitored for 2-3 months, and the weekly baseline iEEG
recordings showed long-term stability. The low-dose group (1 MUL 4-AP, 40 mm, n =
5) exhibited local electrographic seizures without spread to the contralateral
cerebral cortex or brainstem. The high-dose group (5 MUL 4-AP, 40 mm, n = 3) had
several hippocampal electrographic seizures, which spread contralaterally and
triggered brainstem discharges within 40 min, and were associated with violent
motor seizures followed by dyspnea and respiratory arrest, with cortical and
hippocampal iEEG flattening. The group that received high-dose 4-AP without
brainstem implantation (n = 5) had similar seizure-related respiratory
difficulties. Finally, five rats that received high-dose 4-AP without EEG
recording also developed violent motor seizures with postictal respiratory
arrest. Following visualized respiratory arrest in groups III, IV, and V, manual
respiratory resuscitation was successful in five of 13 animals. SIGNIFICANCE:
These studies show that hippocampal seizure activity can spread or trigger
brainstem epileptiform discharges that may cause mortality, possibly mediated by
respiratory network dysfunction.
PMID- 28691205
TI - Risks associated with introduction of poeciliids for control of mosquito larvae:
first record of the non-native Gambusia holbrooki in Argentina.
AB - This study confirms the presence of two species of the non-native mosquitofish
Gambusia in Argentina. The risks that they represent to native biota, their
potential dispersal in the region, and their effectiveness in mosquito larvae
control are discussed.
PMID- 28691206
TI - Duffy null genotype or Fy(a-b-) phenotype are more accurate than self-declared
race for diagnosing benign ethnic neutropenia in Brazilian population.
PMID- 28691207
TI - Hyperuricemia is an independent risk factor for psoriatic arthritis in psoriatic
patients.
AB - Psoriatic arthritis (PsA) is a spondyloarthritic condition mainly seen in
patients with psoriasis. Psoriatic patients with plaques on the scalp, gluteal
fold or nail lesions are known to develop PsA more frequently, but other markers
for PsA have not yet been identified. To determine which psoriatic patients are
at greatest risk of developing PsA, psoriasis vulgaris (PsV) patients who visited
the Department of Dermatology, Fukuoka University Hospital in 2015 were enrolled.
Patients with and without PsA were statistically compared with respect to age,
sex, age at onset, body mass index (BMI), smoking and drinking habits, familial
history of psoriasis and comorbidities. Of 331 patients (237 men, 94 women), 55
had PsA (17%; 39 men, 16 women). PsA patients had significantly higher
frequencies of nail lesions (PsA vs PsV-only, 62% vs 29%; P < 0.0001) and
hyperuricemia (PsA vs PsV-only, 22% vs 9%; P = 0.01). These were confirmed as
independent risk factors for PsA by logistic regression analysis, with odds
ratios of 5.05 for nail lesions (P < 0.0001) and 4.18 for hyperuricemia (P <
0.01). There was no difference in age at onset, sex, BMI and incidence of
diabetes mellitus, hypertension or dyslipidemia. Hyperuricemia is also known to
be more frequent in psoriatic subjects than the normal population. Uric acid
crystals are a strong stimulator of innate immunity. Considering that none of our
cohort had gouty arthritis, hyperuricemia may increase uric acid crystallization
in and around joints, thereby inducing PsA in psoriatic subjects. Hyperuricemia
appears to be an independent risk factor for PsA.
PMID- 28691208
TI - Transcriptomic profile analysis of mouse neural tube development by RNA-Seq.
AB - The neural tube is the primordium of the central nervous system (CNS) in which
its development is not entirely clear. Understanding the cellular and molecular
basis of neural tube development could, therefore, provide vital clues to the
mechanism of neural tube defects (NTDs). Here, we investigated the gene
expression profiles of three different time points (embryonic day (E) 8.5, 9.5
and 10.5) of mouse neural tube by using RNA-seq approach. About 391
differentially expressed genes (DEGs) were screened during mouse neural tube
development, including 45 DEGs involved in CNS development, among which Bmp2,
Ascl1, Olig2, Lhx1, Wnt7b and Eomes might play the important roles. Of 45 DEGs,
Foxp2, Eomes, Hoxb3, Gpr56, Hap1, Nkx2-1, Sez6l2, Wnt7b, Tbx20, Nfib, Cntn1 and
Dcx had different isoforms, and the opposite expression pattern of different
isoforms was observed for Gpr56, Nkx2-1 and Sez6l2. In addition, alternative
splicing, such as mutually exclusive exon, retained intron, skipped exon and
alternative 3' splice site was identified in 10 neural related differentially
splicing genes, including Ngrn, Ddr1, Dctn1, Dnmt3b, Ect2, Map2, Mbnl1, Meis2,
Vcan and App. Moreover, seven neural splicing factors, such as Nova1/2,
nSR100/Srrm4, Elavl3/4, Celf3 and Rbfox1 were differentially expressed during
mouse neural tube development. Interestingly, nine DEGs identified above were
dysregulated in retinoic acid-induced NTDs model, indicating the possible
important role of these genes in NTDs. Taken together, our study provides more
comprehensive information on mouse neural tube development, which might provide
new insights on NTDs occurrence. (c) 2017 IUBMB Life, 69(9):706-719, 2017.
PMID- 28691209
TI - Efficacy of the oral neurokinin-1 receptor antagonist aprepitant for nausea and
vomiting induced by cisplatin and carboplatin in Japanese patients with
gynecological cancer.
AB - AIM: This study was conducted to evaluate the efficacy and the difference in
effects of the oral neurokinin-1(NK-1) receptor antagonist aprepitant for
chemotherapy-induced nausea/vomiting (CINV) in Japanese patients with
gynecological cancer receiving highly emetogenic (cisplatin) and moderately
emetogenic (carboplatin) chemotherapy. METHODS: Aprepitant was added during the
second course of chemotherapy in Japanese patients with grade >= 2 (Common
Terminology Criteria for Adverse Events, version 3.0) nausea and vomiting during
the first course despite receiving antiemetic therapy (a first-generation 5
hydroxytryptamine 3 receptor antagonist + dexamethasone), and in patients who
requested stronger antiemetic therapy despite only having grade 1 nausea and
vomiting. The incidence of nausea and vomiting was compared between the first and
second courses in each group. RESULTS: Ninety-six (55.5%) out of 173 patients
received add-on therapy with aprepitant. There was a significant increase in the
complete response (CR: no vomiting or salvage therapy) rate in the patients
receiving aprepitant, with marked improvement being confirmed for delayed CINV.
Stratified analysis showed that patients with delayed CINV treated with
carboplatin had a significantly higher CR rate, while patients with both acute
and delayed CINV treated with cisplatin had significantly higher CR rates. There
was a positive correlation between the incidence of nausea and the incidence of
vomiting in the patients treated with aprepitant. CONCLUSION: The oral NK-1
receptor antagonist aprepitant could be effective for both acute and delayed CINV
with cisplatin and for delayed CINV with carboplatin in Japanese gynecological
cancer patients.
PMID- 28691210
TI - E3 ligase SAUL1 serves as a positive regulator of PAMP-triggered immunity and its
homeostasis is monitored by immune receptor SOC3.
AB - In both plants and animals, intracellular nucleotide-binding leucine-rich repeat
proteins (NLRs; or Nod-like receptors) serve as immune receptors to recognize
pathogen-derived molecules and mount effective immune responses against microbial
infections. Plant NLRs often guard the presence or activity of other host
proteins, which are the direct virulence targets of pathogen effectors. These
guardees are sometimes immune-promoting components such as those in a mitogen
activated protein kinase cascade. Plant E3 ligases serve many roles in immune
regulation, but it is unclear whether they can also be guarded by NLRs. Here, we
report on an immune-regulating E3 ligase SAUL1, whose homeostasis is monitored by
a Toll interleukin 1 receptor (TIR)-type NLR (TNL), SOC3. SOC3 can associate with
SAUL1, and either loss or overexpression of SAUL1 triggers autoimmunity mediated
by SOC3. By contrast, SAUL1 functions redundantly with its close homolog PUB43 to
promote PAMP-triggered immunity (PTI). Taken together, the E3 ligase SAUL1 serves
as a positive regulator of PTI and its homeostasis is monitored by the TNL SOC3.
PMID- 28691211
TI - Comprehensive profiling of H-Ras signalling in angiosarcoma endothelium.
AB - The MS1/SVR system, in which MS1 represents immortalized endothelial cells and
SVR represents MS1 cells transformed with oncogenic human-rat sarcoma protein (H
Ras), has been used for around 20 years as a valuable tool to study angiogenesis
and carcinogenesis. Despite the use of these cells in numerous studies, a
comprehensive profile of the signalling differences due to oncogenic H-Ras
transformation has not been performed previously. In this study, we profiled the
well-known MS1 and SVR cell lines using a combination of both Western blot and
gene chip assays.
PMID- 28691212
TI - Selenium-Doped Cathodes for Lithium-Organosulfur Batteries with Greatly Improved
Volumetric Capacity and Coulombic Efficiency.
AB - For the first time a new strategy is reported to improve the volumetric capacity
and Coulombic efficiency by selenium doping for lithium-organosulfur batteries.
Selenium-doped cathodes with four sulfur atoms and one selenium atom (as the
doped heteroatom) in the confined structure are designed and synthesized; this
structure exhibits greatly improved volumetric/areal capacities, and a Coulombic
efficiency of almost 100% for highly stable lithium-organosulfur batteries. The
doping of Se significantly enhances the electronic conductivity of battery
electrodes by a factor of 6.2 compared to pure sulfur electrodes, and completely
restricts the production of long-chain lithium polysulfides. This allows
achievement of a high gravimetric capacity of 700 mAh g-1 close to its
theoretical mass capacity, an exceptional volumetric capacity of 2457 mAh cm-3 ,
and excellent capacity retention of 92% after 400 cycles. Shuttle effect is
efficiently weakened since no long-chain polysulfides are detected from in situ
UV/vis results throughout the entire cycling process arising from selenium
doping, which is theoretically confirmed by density functional theory
calculations.
PMID- 28691213
TI - Central cannulation strategy for extent I thoracoabdominal aneurysm repair of
chronic type B aortic dissection.
AB - INTRODUCTION: We evaluated the safety profile of a central cardiopulmonary bypass
(CPB) cannulation strategy for repair of extent I thoracoabdominal aortic
aneurysms (TAAA) with chronic type B dissection in comparison to traditional
peripheral CPB cannulation strategies. METHODS: Patients undergoing extent I TAAA
repair for chronic type B dissection from 2002 to 2011 were retrospectively
reviewed. Patients were grouped by their CPB cannulation strategy. Patients in
Group I underwent central aortic cannulation (n = 28) through a left thoracotomy
incision. The true lumen of the descending thoracic aorta was cannulated using an
echocardiogram-guided Seldinger wire technique. The right atrium was directly
accessed for venous drainage. In Group II (n = 31), arterial and venous
cannulation of the femoral vessels was achieved using a left-sided groin
incision. All patients underwent deep hypothermic circulatory arrest for proximal
aortic reconstruction. RESULTS: Preoperative aortic dimensions (6.5 +/- 0.79 cm
in Group I vs 7.0 +/- 1.15 cm in Group II p = 0.8) were similar between groups.
CPB time (240 +/- 37 min in Group I vs 174 +/- 68 min in Group II p < 0.01) was
significantly higher in the central cannulation group whereas circulatory arrest
times (43 +/- 5 min Group I vs 37 +/- 7 min in Group II p = 0.1) were similar
between the two groups. In-hospital 30-day mortality (N = 0, 0% in Group I; N =
2, 6.5% in Group II), stroke (N = 1, 3.5% in Group I; N = 0, 0% in Group II),
paraplegia (N = 1, 3.5% in Group I; N = 1, 3.2% in Group II), reoperation for
bleeding (N = 1, 3.5% in Group I; N = 1, 3.2% Group II), tracheostomy rate (N =
2, 7% in Group I; N = 3, 9.7% Group II), and mean length of stay (19 days in
Group I vs 17 days in Group II) were similar (p > 0.05). Median follow-up was 3.6
+/- 2.0 in Group I and 5.6 +/- 2.6 years in Group II. Actuarial survival at 5
years was 84.6 % for Group I and 77.6% for Group II (p = 0.52). CONCLUSIONS:
Central true lumen cannulation through a left thoracotomy incision for repair of
extent I TAAA with chronic type B dissection is an acceptable approach with
equivalent early and midterm outcomes compared to more standard femoral
cannulation techniques. It may provide a safe alternative cannulation site for
patients with diseased femoral vessels.
PMID- 28691214
TI - Earthquake Preparedness Among Japanese Hemodialysis Patients in Prefectures
Heavily Damaged by the 2011 Great East Japan Earthquake.
AB - The purpose of this study was to explore the factors related to earthquake
preparedness in Japanese hemodialysis patients. We focused on three aspects of
the related factors: health condition factors, social factors, and the experience
of disasters. A mail survey of all the members of the Japan Association of Kidney
Disease Patients in three Japanese prefectures (N = 4085) was conducted in March,
2013. We obtained 1841 valid responses for analysis. The health factors covered
were: activities of daily living (ADL), mental distress, primary renal diseases,
and the duration of dialysis. The social factors were: socioeconomic status,
family structure, informational social support, and the provision of information
regarding earthquake preparedness from dialysis facilities. The results show that
the average percentage of participants that had met each criterion of earthquake
preparedness in 2013 was 53%. Hemodialysis patients without disabled ADL, without
mental distress, and requiring longer periods of dialysis, were likely to meet
more of the earthquake preparedness criteria. Hemodialysis patients who had
received informational social support from family or friends, had lived with
spouse and children in comparison to living alone, and had obtained information
regarding earthquake preparedness from dialysis facilities, were also likely to
meet more of the earthquake preparedness criteria.
PMID- 28691215
TI - Photochromic Inorganic/Organic Thermoplastic Elastomers.
AB - Photochromic materials are an important class of "smart materials" and are
broadly utilized in technological devices. However, most photochromic materials
reported so far are composed of inorganic compounds that are challenging to
process and suffer from poor mechanical performance, severely limiting their
applications in various markets. In this paper, inorganic photochromic tungsten
trioxide (WO3 ) nanocrystals are conveniently grafted with polymers to hurdle the
deficiency in processability and mechanical properties. This new type of
photochromic material can be thermally processed into desired geometries like
disks and dog-bone specimens. Fully reversible photochromic response under UV
light is also achieved for WO3 -graft polymers, exhibiting tunable response rate,
outperforming the pristine WO3 nanocrystals. Notably, the resulted graft polymers
show extraordinary mechanical performance with excellent ductility (~800%
breaking strain) and relatively high breaking strength (~2 MPa). These
discoveries elucidate an effective pathway to design smart inorganic/organic
hybrid thermoplastic elastomers endowed with outstanding photochromic and
mechanical properties as well as exceptional processability.
PMID- 28691216
TI - Statins and Angiotensin-Converting Enzyme Inhibitors are Associated with Reduced
Mortality and Morbidity in Chronic Liver Disease.
AB - Liver fibrosis is a common response to many chronic liver diseases. The aim of
our study was to explore whether pharmacotherapy for concurrent diseases affects
overall mortality, liver-related mortality and liver-related morbidity in
patients with chronic liver disease. We performed a register-based cohort study
of all patients with a first-time diagnosis of chronic liver disease between 2005
and 2012 in Sweden (n = 70 546). Data from the Patient Register, the Prescribed
Drug Register and the Death Certificate Register were linked. We studied whether
the use of statins, angiotensin-converting enzyme inhibitors, angiotensin
receptor blockers and antibiotics affected the risk of total mortality, liver
specific mortality and morbidity. We found a reduction in mortality risk for
statin users (n = 11,245) with hazard ratios from 0.57 (95% CI: 0.32-0.99) for
patients with autoimmune hepatitis to 0.84 (95% CI: 0.75-0.95) for patients with
alcoholic liver disease. There was a significantly reduced liver-related
mortality for patients with alcoholic liver disease who used angiotensin
converting enzyme inhibitors, 0.85 (95% CI: 0.65-0.96). There were increased
overall mortality risks for antibiotic users (n = 44,572), with hazard ratios up
to 1.67 (95% CI, 1.55-1.80) for viral hepatitis. Statin use was associated with
decreased risks of liver-specific mortality and morbidity, and reduced total
mortality foremost among patients with alcoholic liver disease. Angiotensin
converting enzyme inhibitors was associated with reduced liver-related mortality
among patients with alcoholic liver disease.
PMID- 28691217
TI - Double-Arm Lanthanide Tags Deliver Narrow Gd3+ -Gd3+ Distance Distributions in
Double Electron-Electron Resonance (DEER) Measurements.
AB - Double-arm cyclen-based Gd3+ tags are shown to produce accurate nanometer scale
Gd3+ -Gd3+ distance measurements in double electron-electron resonance (DEER)
experiments by confining the space accessible to the metal ion. The results show
excellent agreement with predictions both for the maximum and width of the
measured distance distributions. For distance measurements in proteins, the tags
can be attached to two cysteine residues located in positions i and i+4, or i and
i+8, of an alpha-helix. In the latter case, an additional mutation introducing an
aspartic acid at position i+4 achieves particularly narrow distribution widths.
The concept is demonstrated with cysteine mutants of T4 lysozyme and maltose
binding protein. We report the narrowest Gd3+ -Gd3+ distance distributions
observed to date for a protein. By limiting the contribution of tag mobility to
the distances measured, double-arm Gd3+ tags open new opportunities to study the
conformational landscape of proteins in solution with high sensitivity.
PMID- 28691218
TI - Safety of a pasteurized plasma-derived Factor VIII and von Willebrand factor
concentrate: analysis of 33 years of pharmacovigilance data.
AB - BACKGROUND: Haemate-P/Humate-P (Humate-P) is a pasteurized human plasma-derived
concentrate containing both Factor VIII and von Willebrand factor for treatment
of hemophilia A and von Willebrand disease (VWD). STUDY DESIGN AND METHODS: We
analyzed the safety of Humate-P based on more than 33 years of postmarketing
pharmacovigilance data, representing an estimated exposure of approximately
25,000 patient-years. The analysis comprises reports of potential adverse drug
reactions (ADRs) from all sources, reported as part of routine pharmacovigilance
at CSL Behring. ADRs considered clinically relevant or potential risks of Humate
P were identified based on defined and standardized Medical Dictionary for
Regulatory Activities queries. Recognizing the limitations of spontaneous
reporting, we also reviewed the literature, including clinical trials with
mandatory reporting. RESULTS: From 1982 to 2015, a total of 670 postmarketing
cases had been reported via pharmacovigilance, for an overall reporting rate of
approximately one ADR per 3900 administered standard doses. Of these cases, 343
involved ADRs considered clinically relevant risks (33 thromboembolic
complications, 97 inhibitor formation, 110 hypersensitivity or allergic
reactions) or potential risks (103 suspected virus transmissions) for Humate-P.
Most thromboembolic complications occurred in patients undergoing surgery or with
other known risk factors. Inhibitor formation occurred mostly in patients with
hemophilia A (24 cases were high titer). Most patients with hypersensitivity or
allergic reactions had VWD. None of the reported suspected virus transmission
cases were confirmed to be associated with Humate-P. Reported results of company
sponsored studies showed a low incidence of adverse events possibly or probably
related to Humate-P. CONCLUSIONS: More than 33 years of pharmacovigilance data
continue to support the safety of Humate-P.
PMID- 28691219
TI - Comparison of reduced field-of-view diffusion-weighted imaging (DWI) and
conventional DWI techniques in the assessment of rectal carcinoma at 3.0T: Image
quality and histological T staging.
AB - PURPOSE: To compare image quality (IQ) of reduced field-of-view (rFOV) and full
FOV (fFOV) diffusion-weighted imaging (DWI) sequences at 3T, with histological T
staging of rectal cancer as a reference standard. MATERIALS AND METHODS: In all,
81 patients with rectal cancer received magnetic resonance (MR) scans (3.0T),
including both rFOV and fFOV DWI sequences. The signal-to-noise ratio (SNR) and
contrast-to-noise ratio (CNR) were quantitatively evaluated using the paired t
test. Two radiologists independently assessed subjective IQ parameters, including
image sharpness, distortion, artifacts, lesion conspicuity, and overall
subjective IQ of both sequences. The Wilcoxon signed rank test was used to
compare subjective IQ scores and tumor apparent diffusion coefficients (ADCs)
between DWI sequences. Spearman correlation analysis was used to correlate ADC
values and corresponding T staging of rectal cancer. RESULTS: CNR was
significantly higher in rFOV DWI than in fFOV DWI (7.15 +/- 2.77 vs. 5.39 +/-
2.08, P < 0.001). SNR was significantly higher in rFOV DWI than in fFOV DWI
(44.17 +/- 11.01 vs. 34.76 +/- 13.30, P < 0.001). The subjective IQ parameters of
rFOV DWI sequence were rated superior to those of fFOV DWI sequence by both
readers (P < 0.001). No significant differences between mean tumor ADC values of
both sequences (0.991 +/- 0.121 vs. 0.100 +/- 0.126 * 10-3 mm2 /s, P = 0.617)
were noted. Apart from T1 stage, T staging of rectal cancer was inversely
correlated with ADC values of rFOV DWI (r = -0.688, P < 0.001) and fFOV DWI
sequences (r = -0.641, P < 0.001). CONCLUSION: The rFOV DWI sequence provided
significantly better IQ and lesion conspicuity than the fFOV DWI sequence. In
addition, rFOV and fFOV DWI sequences can be used in evaluation of histological T
staging of rectal cancer. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 2 J.
Magn. Reson. Imaging 2018;47:967-975.
PMID- 28691220
TI - Mechanistic insights into the liquefaction stage of enzyme-mediated biomass
deconstruction.
AB - Effective enzyme-mediated viscosity reduction, disaggregation, or "liquefaction,"
is required to overcome the rheological challenges resulting from the fibrous,
hygroscopic nature of lignocellulosic biomass, particularly at the high solids
loadings that will be required for an economically viable process. However, the
actual mechanisms involved in enzyme-mediated liquefaction, as determined by
viscosity or yield stress reduction, have yet to be fully resolved. Particle
fragmentation, interparticle interaction, material dilution, and water-retention
capacity were compared for their ability to quantify enzyme-mediated liquefaction
of model and more realistic pretreated biomass substrates. It was apparent that
material dilution and particle fragmentation occurred simultaneously and that
both mechanisms contributed to viscosity/yield stress reduction. However, their
relative importance was dependent on the nature of the biomass substrate.
Interparticle interaction and enzyme-mediated changes to these interactions was
shown to have a significant effect on slurry rheology. Liquefaction was shown to
result from the combined action of material dilution, particle fragmentation, and
alteration of interactions at particle surfaces. However, the observed changes in
water retention capacity did not correlate with yield stress reduction. The
relative importance of each mechanism was significantly influenced by the nature
of the biomass substrate and its physicochemical properties. An ongoing challenge
is that mechanisms, such as refining, which enhance enzyme accessibility to the
cellulosic component of the substrate, are detrimental to slurry rheology and
will likely impede enzyme-mediated liquefaction when high substrate
concentrations are used.
PMID- 28691221
TI - Peanut allergy and isotretinoin: reply to McCarthy et al.
PMID- 28691222
TI - The morphology of the male reproductive system, spermatogenesis and the
spermatozoon of Daphnia magna (Crustacea: Branchiopoda).
AB - This study analyses the histological and cellular morphology of the testis and
sperm development in the male Daphnia magna Straus 1820. Due to the rarity of
males and predominately parthenogenetic lifecycle of Daphnia, there has been
limited detailed information on males in contrast to the well-studied female.
Using light and electron microscopy approaches, we describe the morphology of the
testis during the progression from an immature to mature testis. The testis has
an encasing muscular mesh sheath outside the basal lamina, beneath which is a
thin somatic epithelial cell layer. Internal to the epithelium are the
spermatogonial stem cells and subsequent syncytial clusters of the germ cells as
they progress through spermatogenesis; spermatozoa occupy the entire testis in
sexually mature D. magna. We describe the structure of developing and mature
spermatozoa; mature spermatozoa are non-flagellated, ovoid in shape with
plasmalemma filapodia and are encased in an extracellular capsule.
PMID- 28691223
TI - Letter of response to Greenhawt et al. 'LEAPing Through the Looking Glass:
Secondary Analysis of the Effect of Skin Test Size and Age of Introduction on
Peanut Tolerance after Early Peanut Introduction'.
PMID- 28691226
TI - Of self-lipids, CD1-restricted T cells, and contact sensitization.
AB - Contact hypersensitivity (CHS) in rodents and contact dermatitis in humans are
long-known pathological conditions caused by MHC-restricted T-cell responses.
These responses are triggered upon T-cell recognition of neo-antigenic
determinants, which are generated by a variety of environmental contact
sensitizer (CS) chemicals associating with self-proteins to comprise these neo
antigens. In this issue of the European Journal of Immunology, Betts et al. [Eur.
J. Immunol. 2017. 47: 1171-1180] provide intriguing data implying that common
small molecule CSs such as dinitrochlorobenzene can also recruit and activate
autoreactive CD1-restricted T cells specific for cell-endogenous lipids, which
are enriched in human skin. The effects of dinitrochlorobenzene on CD1 T-cell
recruitment and function were dependent on newly synthesized CD1 molecules and
the presence of endogenous lipids. These findings shed new light on unanticipated
mechanisms that have potential clinical relevance on a common and highly
distressing disease state.
PMID- 28691228
TI - Intra- and post-partum acute aortic dissection (Stanford type B): Report of two
cases.
AB - Pregnancy with Marfan syndrome (MFS) presents challenges to the clinician because
of the increased incidence of maternal cardiovascular complications, including
acute aortic dissection (ADD) and the involvement of the fetus owing to the
urgency of the need for surgery and the low likelihood of survival with premature
delivery. Patient 1 was a 36-year-old pregnant Japanese woman with MFS who was
referred at 16 gestational weeks with aortic root diameter 35.1 mm. Stanford type
B AAD occurred on delivery without evident blood pressure changes. Patient 2 was
a 31-year-old pregnant Japanese woman with MFS with aortic root diameter 28.3 mm
at 20 gestational weeks after David procedure. Ultimately fatal Stanford type B
AAD occurred on post-partum day 15. Both patients were treated with beta-blockers
when AAD occurred. Although these two patients were initially considered to have
relatively low risk according to previous reports and guidelines, AAD occurred.
It is very important to provide information about these high pregnancy risks to
women with MFS before conception, and to follow MFS pregnancies with great
caution.
PMID- 28691227
TI - Changes in the plasma membrane in metabolic disease: impact of the membrane
environment on G protein-coupled receptor structure and function.
AB - : Drug development targeting GPCRs often utilizes model heterologous cell
expression systems, reflecting an implicit assumption that the membrane
environment has little functional impact on these receptors or on their
responsiveness to drugs. However, much recent data have illustrated that membrane
components can have an important functional impact on intrinsic membrane
proteins. This review is directed toward gaining a better understanding of the
structure of the plasma membrane in health and disease, and how this organelle
can influence GPCR structure, function and regulation. It is important to
recognize that the membrane provides a potential mode of lateral allosteric
regulation of GPCRs and can affect the effectiveness of drugs and their
biological responses in various disease states, which can even vary among
individuals across the population. The type 1 cholecystokinin receptor is
reviewed as an exemplar of a class A GPCR that is affected in this way by changes
in the plasma membrane. LINKED ARTICLES: This article is part of a themed section
on Molecular Pharmacology of GPCRs. To view the other articles in this section
visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.21/issuetoc.
PMID- 28691230
TI - Contemporary group estimates adjusted for climatic effects provide a finer
definition of the unknown environmental challenges experienced by growing pigs.
AB - Environmental descriptors derived from mean performances of contemporary groups
(CGs) are assumed to capture any known and unknown environmental challenges. The
objective of this paper was to obtain a finer definition of the unknown
challenges, by adjusting CG estimates for the known climatic effects of monthly
maximum air temperature (MaxT), minimum air temperature (MinT) and monthly
rainfall (Rain). As the unknown component could include infection challenges,
these refined descriptors may help to better model varying responses of sire
progeny to environmental infection challenges for the definition of disease
resilience. Data were recorded from 1999 to 2013 at a piggery in south-east
Queensland, Australia (n = 31,230). Firstly, CG estimates of average daily gain
(ADG) and backfat (BF) were adjusted for MaxT, MinT and Rain, which were fitted
as splines. In the models used to derive CG estimates for ADG, MaxT and MinT were
significant variables. The models that contained these significant climatic
variables had CG estimates with a lower variance compared to models without
significant climatic variables. Variance component estimates were similar across
all models, suggesting that these significant climatic variables accounted for
some known environmental variation captured in CG estimates. No climatic
variables were significant in the models used to derive the CG estimates for BF.
These CG estimates were used to categorize environments. There was no observable
sire by environment interaction (Sire*E) for ADG when using the environmental
descriptors based on CG estimates on BF. For the environmental descriptors based
on CG estimates of ADG, there was significant Sire*E only when MinT was included
in the model (p = .01). Therefore, this new definition of the environment,
preadjusted by MinT, increased the ability to detect Sire*E. While the unknown
challenges captured in refined CG estimates need verification for infection
challenges, this may provide a practical approach for the genetic improvement of
disease resilience.
PMID- 28691229
TI - Desmopressin use for minimising perioperative blood transfusion.
AB - BACKGROUND: Blood transfusion is administered during many types of surgery, but
its efficacy and safety are increasingly questioned. Evaluation of the efficacy
of agents, such as desmopressin (DDAVP; 1-deamino-8-D-arginine-vasopressin), that
may reduce perioperative blood loss is needed. OBJECTIVES: To examine the
evidence for the efficacy of DDAVP in reducing perioperative blood loss and the
need for red cell transfusion in people who do not have inherited bleeding
disorders. SEARCH METHODS: We searched for randomised controlled trials (RCTs) in
the Cochrane Central Register of Controlled Trials (2017, issue 3) in the
Cochrane Library, MEDLINE (from 1946), Embase (from 1974), the Cumulative Index
to Nursing and Allied Health Literature (CINAHL) (from 1937), the Transfusion
Evidence Library (from 1980), and ongoing trial databases (all searches to 3
April 2017). SELECTION CRITERIA: We included randomised controlled trials
comparing DDAVP to placebo or an active comparator (e.g. tranexamic acid,
aprotinin) before, during, or immediately after surgery or after invasive
procedures in adults or children. DATA COLLECTION AND ANALYSIS: We used the
standard methodological procedures expected by Cochrane. MAIN RESULTS: We
identified 65 completed trials (3874 participants) and four ongoing trials. Of
the 65 completed trials, 39 focused on adult cardiac surgery, three on paediatric
cardiac surgery, 12 on orthopaedic surgery, two on plastic surgery, and two on
vascular surgery; seven studies were conducted in surgery for other conditions.
These trials were conducted between 1986 and 2016, and 11 were funded by
pharmaceutical companies or by a party with a commercial interest in the outcome
of the trial.The GRADE quality of evidence was very low to moderate across all
outcomes. No trial reported quality of life. DDAVP versus placebo or no
treatmentTrial results showed considerable heterogeneity between surgical
settings for total volume of red cells transfused (low-quality evidence) and for
total blood loss (very low-quality evidence) due to large differences in baseline
blood loss. Consequently, these outcomes were not pooled and were reported in
subgroups.Compared with placebo, DDAVP may slightly decrease the total volume of
red cells transfused in adult cardiac surgery (mean difference (MD) -0.52 units,
95% confidence interval (CI) -0.96 to -0.08 units; 14 trials, 957 participants),
but may lead to little or no difference in orthopaedic surgery (MD -0.02, 95% CI
0.67 to 0.64 units; 6 trials, 303 participants), vascular surgery (MD 0.06, 95%
CI -0.60 to 0.73 units; 2 trials, 135 participants), or hepatic surgery (MD
0.47, 95% CI -1.27 to 0.33 units; 1 trial, 59 participants).DDAVP probably leads
to little or no difference in the total number of participants transfused with
blood (risk ratio (RR) 0.96, 95% CI 0.86 to 1.06; 25 trials; 1806 participants)
(moderate-quality evidence).Whether DDAVP decreases total blood loss in adult
cardiac surgery (MD -135.24 mL, 95% CI -210.80 mL to -59.68 mL; 22 trials, 1358
participants), orthopaedic surgery (MD -285.76 mL, 95% CI -514.99 mL to -56.53
mL; 5 trials, 241 participants), or vascular surgery (MD -582.00 mL, 95% CI
1264.07 mL to 100.07 mL; 1 trial, 44 participants) is uncertain because the
quality of evidence is very low.DDAVP probably leads to little or no difference
in all-cause mortality (Peto odds ratio (pOR) 1.09, 95% CI 0.51 to 2.34; 22
trials, 1631 participants) or in thrombotic events (pOR 1.36, 95% CI, 0.85 to
2.16; 29 trials, 1984 participants) (both low-quality evidence). DDAVP versus
placebo or no treatment for people with platelet dysfunctionCompared with
placebo, DDAVP may lead to a reduction in the total volume of red cells
transfused (MD -0.65 units, 95% CI -1.16 to -0.13 units; 6 trials, 388
participants) (low-quality evidence) and in total blood loss (MD -253.93 mL, 95%
CI -408.01 mL to -99.85 mL; 7 trials, 422 participants) (low-quality
evidence).DDAVP probably leads to little or no difference in the total number of
participants receiving a red cell transfusion (RR 0.83, 95% CI 0.66 to 1.04; 5
trials, 258 participants) (moderate-quality evidence).Whether DDAVP leads to a
difference in all-cause mortality (pOR 0.72, 95% CI 0.12 to 4.22; 7 trials; 422
participants) or in thrombotic events (pOR 1.58, 95% CI 0.60 to 4.17; 7 trials,
422 participants) is uncertain because the quality of evidence is very low. DDAVP
versus tranexamic acidCompared with tranexamic acid, DDAVP may increase the
volume of blood transfused (MD 0.6 units, 95% CI 0.09 to 1.11 units; 1 trial, 40
participants) and total blood loss (MD 142.81 mL, 95% CI 79.78 mL to 205.84 mL; 2
trials, 115 participants) (both low-quality evidence).Whether DDAVP increases or
decreases the total number of participants transfused with blood is uncertain
because the quality of evidence is very low (RR 2.42, 95% CI 1.04 to 5.64; 3
trials, 135 participants).No trial reported all-cause mortality.Whether DDAVP
leads to a difference in thrombotic events is uncertain because the quality of
evidence is very low (pOR 2.92, 95% CI 0.32 to 26.83; 2 trials, 115
participants). DDAVP versus aprotininCompared with aprotinin, DDAVP probably
increases the total number of participants transfused with blood (RR 2.41, 95% CI
1.45 to 4.02; 1 trial, 99 participants) (moderate-quality evidence).No trials
reported volume of blood transfused or total blood loss and the single trial that
included mortality as an outcome reported no deaths.Whether DDAVP leads to a
difference in thrombotic events is uncertain because the quality of evidence is
very low (pOR 0.98, 95% CI 0.06 to 15.89; 2 trials, 152 participants). AUTHORS'
CONCLUSIONS: Most of the evidence derived by comparing DDAVP versus placebo was
obtained in cardiac surgery, where DDAVP was administered after cardiopulmonary
bypass. In adults undergoing cardiac surgery, the reduction in volume of red
cells transfused and total blood loss was small and was unlikely to be clinically
important. It is less clear whether DDAVP may be of benefit for children and for
those undergoing non-cardiac surgery. A key area for researchers is examining the
effects of DDAVP for people with platelet dysfunction. Few trials have compared
DDAVP versus tranexamic acid or aprotinin; consequently, we are uncertain of the
relative efficacy of these interventions.
PMID- 28691231
TI - Active immunization for prevention of De novo hepatitis B virus infection after
adult living donor liver transplantation with a hepatitis B core antigen-positive
graft.
AB - De novo hepatitis B virus (DNHB) infections may occur in recipients who do not
receive prophylaxis after liver transplantation (LT) with antibody to hepatitis B
core antigen (anti-HBc)-positive donor grafts. Active immunization has been shown
to prevent DNHB in pediatric recipients. Our aim is to investigate the efficacy
of HBV vaccination for preventing DNHB in adult living donor liver
transplantation (LDLT). In total, 71 adult antibody to hepatitis B surface
antigen (anti-HBs)-negative LDLT patients who received anti-HBc+ grafts from 2000
to 2010 were enrolled into this study. Patients were given hepatitis B virus
vaccinations with the aim of achieving anti-HBs > 1000 IU/L before transplant and
>100 IU/L after transplant. The cohort was stratified into 3 groups: patients
with pretransplant anti-HBs titer of > 1000 IU/L without the need for
posttransplant prophylaxis (group 1, n = 24), patients with pretransplant low
titer of <1000 IU/L who were given posttransplant lamivudine prophylaxis and
responded appropriately to posttransplant vaccination by maintaining anti-HBs
titers of > 100 IU/L (group 2, n = 30), and low titer nonresponders (anti-HBs
titer of < 100 IU/L despite vaccination), for whom lamivudine was continued
indefinitely (group 3, n = 17). All DNHB occurred in group 3 patients with
posttransplant anti-HBs levels of < 100 IU/L, with an incidence rate of 17.6%
compared with 0% in patients with posttransplant anti-HBs levels of > 100 IU/L (P
= 0.001). A pretransplant anti-HBs level of >1000 IU/L was significantly
associated with early attainment and a sustained level of posttransplant anti-HBs
of >100 IU/L (P < 0.001). Active immunization is effective in preventing DNHB in
adult LDLT if the posttransplant anti-HBs level is maintained above 100 IU/L with
vaccination. Antiviral prophylaxis can be safely discontinued in patients who
obtain this immunity. Liver Transplantation 23 1266-1272 2017 AASLD.
PMID- 28691232
TI - Successful treatment of continuous intra-arterial administration of prostaglandin
E1, urokinase and heparin for intractable digital ulcers by upper extremity
arterial occlusion in diffuse cutaneous systemic sclerosis patient.
PMID- 28691233
TI - The bias of a two-dimensional view: comparing two-dimensional and three
dimensional mesophyll surface area estimates using noninvasive imaging.
AB - The mesophyll surface area exposed to intercellular air space per leaf area (Sm )
is closely associated with CO2 diffusion and photosynthetic rates. Sm is
typically estimated from two-dimensional (2D) leaf sections and corrected for the
three-dimensional (3D) geometry of mesophyll cells, leading to potential
differences between the estimated and actual cell surface area. Here, we examined
how 2D methods used for estimating Sm compare with 3D values obtained from high
resolution X-ray microcomputed tomography (microCT) for 23 plant species, with
broad phylogenetic and anatomical coverage. Relative to 3D, uncorrected 2D Sm
estimates were, on average, 15-30% lower. Two of the four 2D Sm methods typically
fell within 10% of 3D values. For most species, only a few 2D slices were needed
to accurately estimate Sm within 10% of the whole leaf sample median. However,
leaves with reticulate vein networks required more sections because of a more
heterogeneous vein coverage across slices. These results provide the first
comparison of the accuracy of 2D methods in estimating the complex 3D geometry of
internal leaf surfaces. Because microCT is not readily available, we provide
guidance for using standard light microscopy techniques, as well as recommending
standardization of reporting Sm values.
PMID- 28691234
TI - Stress and welfare in ornamental fishes: what can be learned from aquaculture?
AB - The ornamental fish trade is estimated to handle up to 1.5 billion fishes.
Transportation and handling of fishes imposes a range of stressors that can
result in mortality at rates of up to 73%. These rates vary hugely, however, and
can be as low as 2%, because they are generally estimated rather than based on
experimental work. Given the numbers of ornamental fishes traded, any of the
estimated mortality rates potentially incur significant financial losses and
serious welfare issues. Industry bodies, such as the Ornamental Aquatic Trade
Association (OATA), have established standards and codes of best practice for
handling fishes, but little scientific research has been conducted to understand
the links between stress, health and welfare in ornamental species. In
aquaculture, many of the same stressors occur as those in the ornamental trade,
including poor water quality, handling, transportation, confinement, poor social
and physical environment and disease and in this sector directed research and
some resulting interventions have resulted in improved welfare standards. This
review considers the concept of welfare in fishes and evaluates reported rates of
mortality in the ornamental trade. It assesses how the stress response can be
quantified and used as a welfare indicator in fishes. It then analyses whether
lessons from aquaculture can be usefully applied to the ornamental fish industry
to improve welfare. Finally, this analysis is used to suggest how future research
might be directed to help improve welfare in the ornamental trade.
PMID- 28691235
TI - Outcomes of the conventional and biological treatment approaches for the
management of caries in the primary dentition.
AB - BACKGROUND: In the last few years, conventional restorations including complete
removal of carious tissue (CT) with or without pulp therapy for the treatment of
carious lesions (CL) in primary teeth have been challenged and a more biological
approach has been suggested. This approach involves the use of less invasive
techniques which alter the environment of the CL isolating it from the cariogenic
biofilm and substrate. Two of these treatment approaches that are becoming
increasingly widely accepted and used in paediatric dentistry are the Hall
Technique and indirect pulp capping (IPC). AIM: To investigate the outcome of the
conventional versus the biological approaches for the treatment of deep CL in the
primary teeth in children, delivered in a specialist paediatric dentistry
training environment. DESIGN: This was a retrospective cohort study of 246
children aged 4-9 years, treated with either approach, conventional and
biological, in two UK specialist hospital settings. Data were extracted from
clinical dental records and post-operative radiographs of patients treated during
the period 2006-2012. The outcome of the treatment in this study was categorised
into three main categories: clinical, radiographic, and final outcome. Clinical
and final outcomes were further described as success, minor, and major failure.
RESULTS: In total, 836 primary teeth were included. In the conventional approach,
324 teeth had complete CT removal and 104 teeth had a pulpotomy. In the
biological approach, 388 teeth had Hall Technique preformed metal crowns (PMC)
placed and 20 teeth received indirect pulp capping. PMC were the restoration of
choice for most of the cases where a pulpotomy had been carried out, and resin
composite was most frequently used restorative material for the complete CT
removal group. The majority of the primary teeth treated with either approach
remained asymptomatic after a follow-up period of up to 77 months, 95.3% in the
conventional and 95.8% in the biological. No significant association was found
between the final outcome and the approach used for treatment, age of the
patient, gender and number of carious surfaces or tooth type. CONCLUSION: Both
the conventional and biological treatment approaches had similar final outcomes
and were equally successful for management of CL in the primary dentition.
PMID- 28691236
TI - Response to Vogelstein: How the 2012 AAP Task Force on circumcision went wrong.
AB - Vogelstein cautions medical organizations against jumping into the fray of
controversial issues, yet proffers the 2012 American Academy of Pediatrics' Task
Force policy position on infant male circumcision as 'an appropriate use of
position-statements.' Only a scratch below the surface of this policy statement
uncovers the Task Force's failure to consider Vogelstein's many caveats. The Task
Force supported the cultural practice by putting undeserved emphasis on
questionable scientific data, while ignoring or underplaying the importance of
valid contrary scientific data. Without any effort to quantitatively assess the
risk/benefit balance, the Task Force concluded the benefits of circumcision
outweighed the risks, while acknowledging that the incidence of risks was
unknown. This Task Force differed from other Academy policy-forming panels by
ignoring the Academy's standard quality measures and by not appointing members
with extensive research experience, extensive publications, or recognized
expertise directly related to this topic. Despite nearly 100 publications
available at the time addressing the substantial ethical issues associated with
infant male circumcision, the Task Force chose to ignore the ethical controversy.
They merely stated, with minimal justification, the opinion of one of the Task
Force members that the practice of infant male circumcision is morally
permissible. The release of the report has fostered an explosion of academic
discussion on the ethics of infant male circumcision with a number of national
medical organizations now decrying the practice as a human rights violation.
PMID- 28691238
TI - Structure and ultrastructure of eyes and brains of Thalia democratica (Thaliacea,
Tunicata, Chordata).
AB - Salps are marine planktonic chordates that possess an obligatory alternation of
reproductive modes in subsequent generations. Within tunicates, salps represent a
derived life cycle and are of interest in considerations of the evolutionary
origin of complex anatomical structures and life history strategies. In the
present study, the eyes and brains of both the sexual, aggregate blastozooid and
the asexual, solitary oozooid stage of Thalia democratica (Forskal, ) were
digitally reconstructed in detail based on serial sectioning for light and
transmission electron microscopy. The blastozooid stage of T. democratica
possesses three pigment cup eyes, situated in the anterior ventral part of the
brain. The eyes are arranged in a way that the optical axes of each eye point
toward different directions. Each eye is an inverse eye that consists of two
different cell types: pigment cells (pigc) and rhabdomeric photoreceptor cells
(prcs). The oozooid stage of T. democratica is equipped with a single horseshoe
shaped eye, positioned in the anterior dorsal part of the brain. The opening of
the horseshoe-shaped eye points anteriorly. Similar to the eyes of the
blastozooid, the eye of the oozooid consists of pigment cells and rhabdomeric
photoreceptor cells. The rhabdomeric photoreceptor cells possess apical
microvilli that form a densely packed presumably photosensitive receptor part
adjacent to the concave side of the pigc. We suggest correspondences of the
individual eyes in the blastozooid stage to respective parts of the single
horseshoe-shaped eye in the oozooid stage and hypothesize that the differences in
visual structures and brain anatomies evolved as a result of the aggregate life
style of the blastozooid as opposed to the solitary life style of the oozooid.
PMID- 28691237
TI - Influenza in long-term care facilities.
AB - Long-term care facility environments and the vulnerability of their residents
provide a setting conducive to the rapid spread of influenza virus and other
respiratory pathogens. Infections may be introduced by staff, visitors or new or
transferred residents, and outbreaks of influenza in such settings can have
devastating consequences for individuals, as well as placing extra strain on
health services. As the population ages over the coming decades, increased
provision of such facilities seems likely. The need for robust infection
prevention and control practices will therefore remain of paramount importance if
the impact of outbreaks is to be minimised. In this review, we discuss the nature
of the problem of influenza in long-term care facilities, and approaches to
preventive and control measures, including vaccination of residents and staff,
and the use of antiviral drugs for treatment and prophylaxis, based on currently
available evidence.
PMID- 28691239
TI - Long-term efficacy and safety of aromatase inhibitor use for leiomyomatosis
peritonealis disseminata.
AB - Leiomyomatosis peritonealis disseminata is a rare disease characterized by pelvic
smooth-muscle nodules of various sizes. It is sometimes misdiagnosed as ovarian
or peritoneal carcinoma metastasis; therefore, surgical excision for pathological
diagnosis is required. Treatment options include bilateral salpingo-oophorectomy
(BSO), gonadotrophin-releasing hormone agonist therapy, and aromatase inhibitor
therapy. All of these suppress estrogen levels, but a standard treatment has not
been established. A 40-year-old woman had multiple pelvic tumors, suspicious for
ovarian cancer. She underwent laparotomy, where frozen sections of the nodules
revealed leiomyomatosis peritonealis disseminata. After she completed
gonadotrophin-releasing hormone agonist therapy, we performed a total abdominal
hysterectomy and BSO with residual-nodule resection, but the nodules recurred 6
months after surgery. We then started letrozole, and 3 years have now elapsed
without nodule enlargement or development of new lesions. The long-term use of
aromatase inhibitor therapy is thought to be effective and safe for patients with
recurrence after BSO.
PMID- 28691240
TI - Superdurable Coating Fabricated from a Double-Sided Tape with Long Term "Zero"
Bacterial Adhesion.
AB - There is no coating technology currently available to prevent the notorious
biofilm formation issue. Here, a potential solution to fully address this tough
issue is reported by developing a super-antifouling coating. The use of
zwitterionic hydrogel (a double-sided tape) and commercial superglue is combined
and a durable and ultrarobust antifouling zwitterionic (DURA-Z) coating is
created that can be easily and universally applied on common substrates.
Commercial superglue mostly for binding hydrophobic materials is used to strongly
immobilize the superhydrophilic DURA-Z coating through interpenetration. DURA-Z
coating effectively solves several key challenges preventing the current
antifouling coatings from practical use, including difficult fabrication, low
efficacy, poor toughness, and durability. The fabricated DURA-Z coating retains
antifouling property after 90 d of immersion in water, 50 d of buffer shearing,
and 30 d of water flushing, and after repeated knife scratch and sandpaper
abrasion under 570 kPa. The DURA-Z coating achieves a rarely reported long-term
biofilm resistance to both Gram-positive and Gram-negative bacteria and fungi: it
remains almost "zero" microbe adhesion after continuously challenged by more than
109 cells mL-1 culture medium for 30 d.
PMID- 28691241
TI - Complex autonomic pathways in patients with idiopathic hyperhidrosis.
PMID- 28691242
TI - Bovine colostrum enriched with lyophilized bovine colostrum stimulates intestinal
epithelium renewal of Holstein calves in the first days of life.
AB - Consumption of a second meal of colostrum with high quality could contribute to
the intestinal epithelium development, especially if there is poor supply of
colostrum just after birth. The effect of a second colostrum meal was evaluated
on histomorphometry of the intestinal mucosa of newborn Holstein calves fed with
high- and low-quality first colostrum. Seventy-two calves were fed with a first
colostrum meal with high (HFM, close to 100 mg/ml) or low (LFM, close to 30
mg/ml) IgG concentration. At 12 hr of life, three treatments of second colostrum
feeding were applied to the calves either fed high or low first colostrum: calves
fed with low (LOW-close to 30 mg/ml) or high (HIGH-close to 100 mg/ml) IgG
concentration; and colostrum enriched with lyophilized bovine colostrum with high
IgG concentration (ENRICHED-higher than 120 mg/ml), resulting in six groups.
Intestinal samples were collected after 24 and 72 hr of life. In the distal
jejunum and ileum, LOW showed higher villus height than ENRICHED (p < .05). In
the distal jejunum, greater villus perimeter was observed in the LOW compared to
ENRICHED at 24 hr (p < .05). In ileum, LFM showed higher villus perimeter
compared to HFM (p < .05). LOW showed the highest villus height-to-crypt depth
ratio in the medium and distal jejunum and ileum, p < .05. ENRICHED and HFM
showed decreased muscle layer thickness in the proximal and distal jejunum
respectively (p < .05). The results reveal that the high concentration of total
solids, crude protein, IgG and IGF-I of colostrum with high quality worsened the
absorptive area, but may have stimulated the activity of cell division in
intestinal crypts. Considering the present results, bovine colostrum enriched
with lyophilized bovine colostrum stimulates intestinal epithelium renewal of
Holstein calves in the first days of life.
PMID- 28691243
TI - The health-related quality of life of patients with prostate cancer and their
spouses before treatment compared with the general population.
AB - AIMS: To describe the health-related quality of life (HRQOL) of patients with
prostate cancer and their spouses in comparison with the Finnish general
population, using the RAND 36-Item Health Survey. An additional purpose was to
describe the associations between the background variables of the participants
and their HRQOL. BACKGROUND: The HRQOL of patients with prostate cancer and
especially their spouses at the time of diagnosis is not well known. DESIGN: A
cross-sectional study. METHODS: Responses were received from 232 patients and 229
spouses at 5 central hospitals in Finland between October 2013 and January 2016.
RESULTS: Compared to the Finnish general population mean, the HRQOL of the
patients and their spouses was, on average, better for all dimensions. Patients'
age, the presence of disease, and the treatment method were associated with the
dimensions of HRQOL. The dimensions of HRQOL were also associated with spouses'
age, basic and vocational education, and the presence of disease. CONCLUSION: The
patients and their spouses experienced their HRQOL as very similar; however, on
average, it is better than the general population mean. However, the evidence
suggests that support from the nurses should focus on emotional well-being, the
dimension that received the lowest scores in both groups.
PMID- 28691244
TI - Probiotics intake from proximal or distal gastrointestinal tract: The
investigation on intestinal morphology and performance of Japanese quail.
AB - The aim of the present study was to investigate the efficacy of early single-dose
probiotics administered from proximal or distal gastrointestinal tract on quails'
performance and small intestinal morphology. A total of 120 Japanese quail
(Coturnix coturnix japonica) 1-d-old chicks were divided into the following
experimental groups before being transferred to the raising room: (i) control (no
probiotic administered); (ii) oral group (received probiotics via oesophageal
gavage); and (iii) vent lip group (received probiotics directly into vent). Four
replicates of 10 chicks per cage were considered for each treatment and birds
were raised up to 35 days in the same conditions with ad libitum access to feed
and water. A commercial probiotics (Protexin, Somerset, UK) used in this study
contained 2 * 109 cfu/g of nine different micro-organisms. On day 35, all birds
were weighed and then three birds in every pen were killed via cervical
dislocation. Two cm of mid-point of duodenum and ileum were cut for
histomorphology assays. Both probiotics-treated groups had higher body weight and
body weight gain than control (p < .01). Ileum was longer in probiotics-treated
groups than in the control (p < .01). Orally treated birds had the highest
duodenum villus height and crypt depth (p < .01). In the cloacally treated
quails, ileum villus length was higher than the both other groups, and crypts'
depth was deeper than the control (p < .01). The numbers of both types of goblet
cells (acidic mucin producer and neutral mucin producer) were higher in the birds
receiving probiotics than control birds (p < .01). Although there were no
statistical differences in performance values between the different ways of
probiotics entrance into gut, some intestinal histomorphometric parameters were
improved in ileum of the birds receiving probiotics through distal gut that is
cloaca (p < .01).
PMID- 28691245
TI - Synthesis of Chlorine-Substituted Graphdiyne and Applications for Lithium-Ion
Storage.
AB - Chlorine-substituted graphdiyne (Cl-GDY) is prepared through a Glaser-Hay
coupling reaction on the copper foil. Cl-GDY is endowed with a unique pi
conjugated carbon skeleton with expanded pore size in two dimensions, having
graphdiyne-like sp- and sp2 - hybridized carbon atoms. As a result, the transfer
tunnels for lithium (Li) ions in the perpendicular direction of the molecular
plane are enlarged. Moreover, benefiting from the bottom-to-up fabrication
procedure of graphdiyne and the strong chemical tailorability of the alkinyl
contained monomer, the amount of substitutional chlorine atoms with appropriate
electronegativity and atom size is high and evenly distributed on the as-prepared
carbon framework, which will synergistically stabilize the Li intercalated in the
Cl-GDY framework, and thus generate more Li storage sites. Profiting from the
above unique structure, Cl-GDY shows remarkable electrochemical properties in
lithium ion half-cells.
PMID- 28691246
TI - Formation and function of the "Xestoleberis-spot" in Xestoleberis hanaii
(Crustacea: Ostracoda).
AB - The crescent sculpture of the so-called "Xestoleberis-spot" develops inside the
calcified valve of the family Xestoleberididae. Electron microscopic observations
on both, intermoult and postmoult stages of Xestoleberis species reveal that the
"Xestoleberis-spot" system consists of three elements; two calcified chambers, a
vesicle of electron-dense material and an uncalcified procuticle. The formation
and function of the "Xestoleberis-spot" system are discussed. In conclusion, the
"Xestoleberis-spot" system functions as the muscle attachment site for several
antennal muscles, and provides the material for chitinous fibers in the
exocuticle of outer lamella. The unique cuticular structures of the family
Xestoleberididae are due to the "Xestoleberis-spot" system.
PMID- 28691247
TI - Crystal structure of the UBR-box from UBR6/FBXO11 reveals domain swapping
mediated by zinc binding.
AB - The UBR-box is a 70-residue zinc finger domain present in the UBR family of E3
ubiquitin ligases that directly binds N-terminal degradation signals in substrate
proteins. UBR6, also called FBXO11, is an UBR-box containing E3 ubiquitin ligase
that does not bind N-terminal signals. Here, we present the crystal structure of
the UBR-box domain from human UBR6. The dimeric crystal structure reveals a
unique form of domain swapping mediated by zinc coordination, where three
independent protein chains come together to regenerate the topology of the
monomeric UBR-box fold. Analysis of the structure suggests that the absence of N
terminal residue binding arises from the lack of an amino acid binding pocket.
PMID- 28691249
TI - Seasonal or pathological findings? Morphofunctional characteristics of the equine
endometrium during the autumn and spring transition.
AB - The deep anoestrous phase in winter is part of the anovulatory season in mares
and is bordered by the autumn and spring transitional periods (ATP/STP). To
define an annual time span for effective prognostic biopsy sampling, the aim of
this study was to provide a morphofunctional characterization of the endometrium
during ATP and STP. To outline both transitional periods, endometrial specimens
were taken in September, October and November (n = 76) as well as February, March
and April (n = 184) with the requirement of a detailed clinical documentation.
Tissue samples were examined histologically with special emphasis on the
functional endometrial morphology. Additionally, an immunohistochemical
evaluation was performed on selected specimens regarding the expression of
oestrogen receptor alpha, progesterone receptor and Ki67-antigen. An absent to
low endometrial activity was ascertained in more than 60% of all specimens from
late October onwards, whereas a comparably lacking or low activity in STP was
observed until early April. Approximately 30% (ATP) to 22% (STP) of all samples
exhibited a predominantly "irregular" endometrial differentiation. During the
transitional periods, the clinically evaluated ovarian status (transrectal
palpation, transrectal ultrasonography and/or serum progesterone and oestrogen
analyses) and the endometrial functional morphology were in accordance with
approximately 70% of all cases. The expression of steroid hormone receptors and
Ki67-antigen was generally low. Given that endometrial maldifferentiations were
frequently found during ATP and STP, its occurence might display a characteristic
and physiological feature of the transitional periods. Regarding the functional
endometrial morphology, a diagnostic biopsy sampling should therefore be
performed between late April and before September.
PMID- 28691248
TI - Adolescent alcohol exposure decreases frontostriatal resting-state functional
connectivity in adulthood.
AB - Connectivity of the prefrontal cortex (PFC) matures through adolescence,
coinciding with emergence of adult executive function and top-down inhibitory
control over behavior. Alcohol exposure during this critical period of brain
maturation may affect development of PFC and frontolimbic connectivity. Adult
rats exposed to adolescent intermittent ethanol (AIE; 5 g/kg ethanol, 25 percent
v/v in water, intragastrically, 2-day-on, 2-day-off, postnatal day 25-54) or
water control underwent resting-state functional MRI to test the hypothesis that
AIE induces persistent changes in frontolimbic functional connectivity under
baseline and acute alcohol conditions (2 g/kg ethanol or saline,
intraperitoneally administered during scanning). Data were acquired on a Bruker
9.4-T MR scanner with rats under dexmedetomidine sedation in combination with
isoflurane. Frontolimbic network regions-of-interest for data analysis included
PFC [prelimbic (PrL), infralimbic (IL), and orbitofrontal cortex (OFC) portions],
nucleus accumbens (NAc), caudate putamen (CPu), dorsal hippocampus, ventral
tegmental area, amygdala, and somatosensory forelimb used as a control region.
AIE decreased baseline resting-state connectivity between PFC subregions (PrL-IL
and IL-OFC) and between PFC-striatal regions (PrL-NAc, IL-CPu, IL-NAc, OFC-CPu,
and OFC-NAc). Acute ethanol induced negative blood-oxygen-level-dependent changes
within all regions of interest examined, along with significant increases in
functional connectivity in control, but not AIE animals. Together, these data
support the hypothesis that binge-like adolescent alcohol exposure causes
persistent decreases in baseline frontolimbic (particularly frontostriatal)
connectivity and alters sensitivity to acute ethanol-induced increases in
functional connectivity in adulthood.
PMID- 28691250
TI - Obesity in patients with major depression is related to bipolarity and mixed
features: evidence from the BRIDGE-II-Mix study.
AB - OBJECTIVES: The Bipolar Disorders: Improving Diagnosis, Guidance and Education
(BRIDGE)-II-Mix study aimed to estimate the frequency of mixed states in patients
with a major depressive episode (MDE) according to different definitions. The
present post-hoc analysis evaluated the association between obesity and the
presence of mixed features and bipolarity. METHODS: A total of 2811 MDE subjects
were enrolled in a multicenter cross-sectional study. In 2744 patients, the body
mass index (BMI) was evaluated. Psychiatric symptoms, and sociodemographic and
clinical variables were collected, comparing the characteristics of MDE patients
with (MDE-OB) and without (MDE-NOB) obesity. RESULTS: Obesity (BMI >=30) was
registered in 493 patients (18%). In the MDE-OB group, 90 patients (20%)
fulfilled the DSM-IV-TR criteria for bipolar disease (BD), 225 patients (50%)
fulfilled the bipolarity specifier criteria, 59 patients (13%) fulfilled DSM-5
criteria for MDEs with mixed features, and 226 patients (50%) fulfilled Research
Based Diagnostic Criteria for an MDE. Older age, history of (hypo)manic switches
during antidepressant treatment, the occurrence of three or more MDEs, atypical
depressive features, antipsychotic treatment, female gender, depressive mixed
state according to DSM-5 criteria, comorbid eating disorders, and anxiety
disorders were significantly associated with the MDE-OB group. Among (hypo)manic
symptoms during the current MDE, psychomotor agitation, distractibility,
increased energy, and risky behaviors were the variables most frequently
associated with MDE-OB group. CONCLUSIONS: In our sample, the presence of obesity
in patients with an MDE seemed to be associated with higher rates of bipolar
spectrum disorders. These findings suggest that obesity in patients with an MDE
could be considered as a possible marker of bipolarity.
PMID- 28691251
TI - Postmarketing withdrawal of human medicinal products because of adverse reactions
in animals: a systematic review and analysis.
AB - PURPOSE: We have identified human medicinal products for which animal data were
used as evidence for withdrawal, determined whether the adverse reactions were
reported in humans, established whether confirmatory human studies were
conducted, and explored the withdrawal patterns over time. METHODS: We searched
the World Health Organization's Consolidated List of [Medicinal] Products, drug
regulatory authorities' websites, PubMed, Google Scholar, and selected textbooks
to identify medicinal products withdrawn from 1950 to June 2016. We included
medicinal products for which animal data were specifically reported as a reason
for withdrawal. We used a checklist adapted from the International Agency for
Research on Cancer criteria to rate the evidence. RESULTS: In 37 cases, evidence
from animals was the reason given for withdrawal between 1963 and 2000. Evidence
of carcinogenicity was cited in 23 cases (62%). Limited evidence for harms
occasioned withdrawal in over 80% of cases. In 11 cases (30%), the adverse drug
reactions were subsequently reported in humans. In 5 instances (14%), formal
studies were conducted in humans. The median interval to withdrawal following
reports of adverse reactions was 2 years (IQR = 1-9 y). CONCLUSIONS: Regulatory
authorities and drug manufacturers are likely to withdraw medicinal products
quickly from the market when animal experiments suggest increased risks of
cancers or congenital malformations. Human studies are seldom conducted when
harms are suspected in animals. Future research should explore better methods of
extrapolating harms data from animal research to humans.
PMID- 28691252
TI - Peptide backbone circularization enhances antifreeze protein thermostability.
AB - Antifreeze proteins (AFPs) are a class of ice-binding proteins that promote
survival of a variety of cold-adapted organisms by decreasing the freezing
temperature of bodily fluids. A growing number of biomedical, agricultural, and
commercial products, such as organs, foods, and industrial fluids, have benefited
from the ability of AFPs to control ice crystal growth and prevent ice
recrystallization at subzero temperatures. One limitation of AFP use in these
latter contexts is their tendency to denature and irreversibly lose activity at
the elevated temperatures of certain industrial processing or large-scale AFP
production. Using the small, thermolabile type III AFP as a model system, we
demonstrate that AFP thermostability is dramatically enhanced via split intein
mediated N- and C-terminal end ligation. To engineer this circular protein,
computational modeling and molecular dynamics simulations were applied to
identify an extein sequence that would fill the 20-A gap separating the free ends
of the AFP, yet impose little impact on the structure and entropic properties of
its ice-binding surface. The top candidate was then expressed in bacteria, and
the circularized protein was isolated from the intein domains by ice-affinity
purification. This circularized AFP induced bipyramidal ice crystals during ice
growth in the hysteresis gap and retained 40% of this activity even after
incubation at 100 degrees C for 30 min. NMR analysis implicated enhanced
thermostability or refolding capacity of this protein compared to the noncyclized
wild-type AFP. These studies support protein backbone circularization as a means
to expand the thermostability and practical applications of AFPs.
PMID- 28691253
TI - Cardiovascular disease risk in patients receiving organ transplantation: a
national cohort study.
AB - Although organ transplantation is the definitive treatment for end-stage organ
failure, the post-transplant outcomes can be substantially influenced by
cardiovascular complications. A national cohort study was performed to estimate
risks of cardiovascular diseases in those with heart, lung, kidney, and liver
transplantation. This cohort study consisted of 5978 solid organ transplantations
identified using the Taiwan National Health Insurance Database. Cardiovascular
and mortality risks in transplant recipients were evaluated using standardized
incidence ratios, excess absolute risks, and standardized mortality ratios as
compared to those in the general population. In heart, kidney, and liver
recipients, the standardized incidence ratios of overall cardiovascular diseases
were 9.41 (7.75-11.44), 3.32 (2.29-3.77), and 1.4 (1.15-1.7) and the overall
standardized mortality ratios were 5.23 (4.54-6.03), 1.48 (1.34-1.63), and 3.95
(3.64-4.28), respectively. Except for heart organ recipients who were at highest
risk for coronary artery disease with a standardized incidence ratio of 13.12
(10.57-16.29), kidney and liver organ recipients had a ninefold increased risk in
developing deep vein thrombosis post-transplant. In conclusion, solid organ
transplant patients are at risk of cardiovascular disease, in particular, deep
vein thrombosis, which may warrant early identification of high-risk patients in
addition to prompt and adequate thromboprophylaxis perioperatively.
PMID- 28691254
TI - Response to Intervention as a Predictor of Long-Term Reading Outcomes in Children
with Dyslexia.
AB - The goal of this study was to investigate how growth during a phonics-based
intervention, as well as reading levels at baseline testing, predicted long-term
reading outcomes of children with dyslexia. Eighty Dutch children with dyslexia
who had completed a 50-week phonics-based intervention in grade 4 were tested in
grade 5 on both word and pseudoword (following regular Dutch orthographic
patterns) reading efficiency and compared to 93 typical readers. In grade 5 the
children with dyslexia were still significantly slower in word and pseudoword
reading than their typically developing peers. Results showed that long-term
pseudoword reading in the group with dyslexia was predicted by pseudoword reading
at pretest and growth in pseudoword reading during the intervention, which was
itself predicted by pseudoword reading at pretest. This was not the case for word
reading. We found that long-term word reading was directly predicted from pretest
word reading, and indirectly via pretest pseudoword reading, via growth in
pseudoword and word reading. It can be concluded that pseudoword reading is not
only a good indicator of severity of reading difficulties in children with
dyslexia, it is also an indicator of who will profit from intervention in the
long-term. Copyright (c) 2017 John Wiley & Sons, Ltd.
PMID- 28691255
TI - Impact of human papillomavirus on outcome in patients with oropharyngeal cancer
treated with primary surgery.
AB - BACKGROUND: Knowledge about prognostic factors in surgically treated patients
with oropharyngeal squamous cell carcinoma (SCC) is limited. The purpose of this
study was to identify influential factors on survival in a large cohort of
patients with surgically treated oropharyngeal SCC. METHODS: Retrospective
analysis of survival estimates in patients with surgically treated oropharyngeal
SCC using tumoral positivity for human papillomavirus (HPV) and risk-of-death
categories according to a study from 2010 as stratification factors. RESULTS: The
5-year overall survival (OS) and disease-specific survival (DSS) rates after
surgery alone were higher in HPV-associated oropharyngeal SCC (OS 80% vs 62%; P =
.01; DSS 92% vs 76%; P = .03). Patients in the low-risk category had higher
survival rates (OS 91%; DSS 99%) than patients in the intermediate-risk group (OS
63%; DSS 83%), and high-risk group (OS 61%; DSS 75%). CONCLUSION: Nonsmokers with
HPV-positive oropharyngeal SCC have a better prognosis than smokers with HPV
positive oropharyngeal SCC and also than patients with HPV-negative tumors when
treated by surgery alone.
PMID- 28691256
TI - Clinical usefulness of MLCs in robotic radiosurgery systems for prostate SBRT.
AB - Stereotactic body radiation therapy (SBRT) using recently introduced multileaf
collimators (MLC) is preferred over circular collimators in the treatment of
localized prostate cancer. The objective of this study was to assess the clinical
usefulness of MLCs in prostate SBRT by comparing the effectiveness of treatment
plans using fixed collimators, variable collimators, and MLCs and by ensuring
delivery quality assurance (DQA) for each. For each patient who underwent
conventional radiation therapy for localized prostate cancer, mock SBRT plans
were created using a fixed collimator, a variable collimator, and an MLC. The
total MUs, treatment times, and dose-volume histograms of the planning target
volumes and organs at risk for each treatment plan were compared. For DQA, a
phantom with a radiochromic film or an ionization chamber was irradiated in each
plan. We performed gamma-index analysis to evaluate the consistency between the
measured and calculated doses. The MLC-based plans had an ~27% lower average
total MU than the plans involving other collimators. Moreover, the average
estimated treatment time for the MLC plan was 31% and 20% shorter than that for
the fixed and variable collimator plans respectively. The gamma-index passing
rate in the DQA using film measurements was slightly lower for the MLC than for
the other collimators. The DQA results acquired using the ionization chamber
showed that the discrepancies between the measured and calculated doses were
within 3% in all cases. The results reinforce the usefulness of MLCs in robotic
radiosurgery for prostrate SBRT treatment planning; most notably, the total MU
and treatment time were both reduced compared to the cases using other types of
collimators. Moreover, although the DQA results based on film dosimetry yielded a
slightly lower gamma-index passing rate for the MLC than for the other
collimators, the MLC accuracy was determined to be sufficient for clinical use.
PMID- 28691257
TI - tbx6l and tbx16 are redundantly required for posterior paraxial mesoderm
formation during zebrafish embryogenesis.
AB - BACKGROUND: T-box genes encode a large transcription factor family implicated in
many aspects of development. We are focusing on two related zebrafish T-box
genes, tbx6l and tbx16, that are expressed in highly overlapping patterns in
embryonic paraxial mesoderm. tbx16 mutants are deficient in trunk, but not tail,
somites; we explored whether presence of tail somites in tbx16 mutants was due to
compensatory function provided by the tbx6l gene. RESULTS: We generated two
zebrafish tbx6l mutant alleles. Loss of tbx6l has no apparent effect on embryonic
development, nor does tbx6l loss enhance the phenotype of two other T-box gene
mutants, ta and tbx6, or of the mesp family gene mutant msgn1. In contrast, loss
of tbx6l function dramatically enhances the paraxial mesoderm deficiency of tbx16
mutants. CONCLUSIONS: These data demonstrate that tbx6l and tbx16 genes function
redundantly to direct tail somite development. tbx6l single mutants develop
normally because tbx16 fully compensates for loss of tbx6l function. However,
tbx6l only partially compensates for loss of tbx16 function. These results
resolve the question of why loss of function of tbx16 gene, which is expressed
throughout the ventral and paraxial mesoderm, profoundly affects somite
development in the trunk but not the tail. Developmental Dynamics 246:759-769,
2017. (c) 2017 Wiley Periodicals, Inc.
PMID- 28691258
TI - Differences between gastric signet-ring cell carcinoma and poorly differentiated
adenocarcinoma: A comparison of histopathologic features determined by mucin core
protein and trefoil factor family peptide immunohistochemistry.
AB - We investigated differences between the pathological features of gastric signet
ring cell carcinoma (sig) and poorly differentiated adenocarcinoma (por) by
examining the expressions of the trefoil factor family peptides (TFFs) and mucin
core proteins (MUCs). Ninety-seven tissues of 97 gastric cancer patients were
selected for this study. After gastrectomy, the major histopathologic types were
determined to be sig, solid-type poorly differentiated adenocarcinoma (por1), non
solid type poorly differentiated adenocarcinoma (por2), and well-differentiated
tubular adenocarcinoma (tub1). We evaluated the prevalence of positive staining
for MUCs (MUC5AC and MUC2) and TFFs (TFF1 and TFF3) and assessed the correlation
between MUCs and TFFs in each histopathological type. The rate of MUC2 expression
significantly differed between sig and por2 (50.0% vs 11.7%, P = 0.011). TFF3
expression in sig significantly differed from TFF3 expression in both por2 (100%
vs 17.6%, P < 0.0001) and por1 (100% vs 33.3%, P = 0.0004). MUC5AC and TFF1
expressions were significantly correlated in por1 (r = 0.705, P = 0.002), por2 (r
= 0.535, P = 0.0009), and tub1 (r = 0.470, P = 0.0034), while MUC2 and TFF3
expressions were significantly correlated only in sig (r = 0.593, P = 0.040). The
expression and correlation patterns of the TFFs and MUCs suggest that the
histopathologic features of gastric sig differ from those of por.
PMID- 28691259
TI - Trigeminal trophic syndrome: Analysis of the number of peripheral nerve fibres
and blood vessels in the lesional skin.
PMID- 28691260
TI - Semantic fluency in deaf children who use spoken and signed language in
comparison with hearing peers.
AB - BACKGROUND: Deafness has an adverse impact on children's ability to acquire
spoken languages. Signed languages offer a more accessible input for deaf
children, but because the vast majority are born to hearing parents who do not
sign, their early exposure to sign language is limited. Deaf children as a whole
are therefore at high risk of language delays. AIMS: We compared deaf and hearing
children's performance on a semantic fluency task. Optimal performance on this
task requires a systematic search of the mental lexicon, the retrieval of words
within a subcategory and, when that subcategory is exhausted, switching to a new
subcategory. We compared retrieval patterns between groups, and also compared the
responses of deaf children who used British Sign Language (BSL) with those who
used spoken English. We investigated how semantic fluency performance related to
children's expressive vocabulary and executive function skills, and also retested
semantic fluency in the majority of the children nearly 2 years later, in order
to investigate how much progress they had made in that time. METHODS &
PROCEDURES: Participants were deaf children aged 6-11 years (N = 106, comprising
69 users of spoken English, 29 users of BSL and eight users of Sign Supported
English-SSE) compared with hearing children (N = 120) of the same age who used
spoken English. Semantic fluency was tested for the category 'animals'. We coded
for errors, clusters (e.g., 'pets', 'farm animals') and switches. Participants
also completed the Expressive One-Word Picture Vocabulary Test and a battery of
six non-verbal executive function tasks. In addition, we collected follow-up
semantic fluency data for 70 deaf and 74 hearing children, nearly 2 years after
they were first tested. OUTCOMES & RESULTS: Deaf children, whether using spoken
or signed language, produced fewer items in the semantic fluency task than
hearing children, but they showed similar patterns of responses for items most
commonly produced, clustering of items into subcategories and switching between
subcategories. Both vocabulary and executive function scores predicted the number
of correct items produced. Follow-up data from deaf participants showed
continuing delays relative to hearing children 2 years later. CONCLUSIONS &
IMPLICATIONS: We conclude that semantic fluency can be used experimentally to
investigate lexical organization in deaf children, and that it potentially has
clinical utility across the heterogeneous deaf population. We present normative
data to aid clinicians who wish to use this task with deaf children.
PMID- 28691261
TI - Hyperphosphatasemia in leiomyosarcoma of the uterus: Two case reports and a
literature review.
AB - Some tumors are known to produce alkaline phosphatase (ALP). Seven cases of
uterine leiomyosarcoma were identified from the clinical records of Sakai City
Medical Center from January 2006 to December 2014. Patients' ages ranged from 47
to 75 years (median: 58). Clinical stages were IB, IIB, IIIA, and IVB in four,
one, one, and one cases, respectively. Of these, two were found to have
hyperphosphatasemia before surgery, and the elevated ALP level decreased after
surgery, and increased with disease recurrence. In the cases of
hyperphosphatasemia, leiomyosarcoma cells showed positive staining for ALP. There
was no correlation between serum ALP and lactate dehydrogenase, or ALP and cancer
antigen 125. The combination of ALP, lactate dehydrogenase, and cancer antigen
125 may be more useful for diagnosis and follow-up of leiomyosarcoma.
PMID- 28691262
TI - Metabolic modeling to identify engineering targets for Komagataella phaffii: The
effect of biomass composition on gene target identification.
AB - Genome-scale metabolic models are valuable tools for the design of novel strains
of industrial microorganisms, such as Komagataella phaffii (syn. Pichia
pastoris). However, as is the case for many industrial microbes, there is no
executable metabolic model for K. phaffiii that confirms to current standards by
providing the metabolite and reactions IDs, to facilitate model extension and
reuse, and gene-reaction associations to enable identification of targets for
genetic manipulation. In order to remedy this deficiency, we decided to
reconstruct the genome-scale metabolic model of K. phaffii by reconciling the
extant models and performing extensive manual curation in order to construct an
executable model (Kp.1.0) that conforms to current standards. We then used this
model to study the effect of biomass composition on the predictive success of the
model. Twelve different biomass compositions obtained from published empirical
data obtained under a range of growth conditions were employed in this
investigation. We found that the success of Kp1.0 in predicting both gene
essentiality and growth characteristics was relatively unaffected by biomass
composition. However, we found that biomass composition had a profound effect on
the distribution of the fluxes involved in lipid, DNA, and steroid biosynthetic
processes, cellular alcohol metabolic process, and oxidation-reduction process.
Furthermore, we investigated the effect of biomass composition on the
identification of suitable target genes for strain development. The analyses
revealed that around 40% of the predictions of the effect of gene overexpression
or deletion changed depending on the representation of biomass composition in the
model. Considering the robustness of the in silico flux distributions to the
changing biomass representations enables better interpretation of experimental
results, reduces the risk of wrong target identification, and so both speeds and
improves the process of directed strain development.
PMID- 28691263
TI - Stenting the vertical ductus arteriosus via axillary artery access using "wire
target" technique.
AB - OBJECTIVES: To retrospectively review the outcome of stent placement in neonates
with a vertical ductus, present a technique of ductal stenting via the axillary
artery and compare it to ductal stening via the femoral venous access. DESIGN:
Nineteen patients with duct-dependent pulmonary circulations through a vertical
ductus arteriosus were treated with stent implantation. Those patients were
retrospectively included in the study. In the first nine of these cases, stent
delivery was done transvenously. In the latter ten cases, we favored the axillary
artery access to the transvenous approach for stenting the vertical ductus
arteriosus. Wire-target technique was used to attain access to axillary artery.
RESULTS: PDA stenting was successful in six out of nine cases in whom the
procedure was done anterogradely via the femoral vein and in all cases in whom
the procedure was done via axillary artery (P = .047). Wire-target technique was
used successfully in all ten cases in whom the procedure was done via axillary
artery. Fluoroscopy time and total procedure time were significantly shorter in
patients in whom the procedure was done via axillary artery (P < .001)
CONCLUSIONS: Stenting of a vertical ductus arteriosus via the axillary artery
using wire-target technique is feasible and safe in selected patients.
PMID- 28691264
TI - Redundant publication and salami slicing: the significance of splitting data.
PMID- 28691265
TI - Long-term ventilation in spinal muscular atrophy: the price of progress.
PMID- 28691266
TI - Empowerment of family caregivers of adults and elderly persons: A concept
analysis.
AB - AIM: This concept analysis defined and described the components of empowerment of
family caregivers who care for adults and the elderly. METHODS: Rodgers
evolutionary method of concept analysis was used. Data sources included Pub Med,
CINAHL, Scopus, and Igaku Chuo Zasshi. Thirty articles published between 1995 and
2015 focusing on the empowerment of family caregivers providing care to adults
and the elderly were selected. RESULT: The analysis reveals 6 attributes, 5
antecedents, and 5 consequences. In addition, the results reveal structured
aspects of family caregivers, care receivers, and other people surrounding them,
and their relationships. Empowerment of adults' and elders' family caregivers may
be defined as "positive control of one's mind and body, cultivating a positive
attitude, proactively attempting to understand one's role as a caregiver to
improve caregiving capabilities, focusing on others as well as oneself,
supporting the independence of the care receiver, and creating constructive
relationships with other people surrounding them." CONCLUSION: The components of
empowerment clarified in this research can be used for the measurement of and
interventions aimed at improving empowerment among family caregivers.
Furthermore, clarifying the definition of empowerment among family caregivers
enables researchers to better distinguish empowerment from similar concepts in
the future.
PMID- 28691267
TI - The use of virtual patient scenarios as a vehicle for teaching professionalism.
AB - OBJECTIVES: This study aimed to measure students' perceptions of virtual patient
scenarios (VPs) for developing ethical reasoning skills and to explore features
in VP design that are necessary to promote professionalism. METHODS: Sixty-five
dental students participated in learning sessions that involved collaborative
practice with five VPs (four high fidelity and one low fidelity), followed by
reflection sessions. Students' perceptions towards the use of VPs in developing
ethical reasoning skills were assessed using a questionnaire that involved 10
closed and three open-ended questions. RESULTS: High-fidelity VPs were perceived
as significantly better for developing ethical reasoning skills than low-fidelity
VPs. Analyses of answers to open-ended questions revealed two new features that
are specific for VPs intended for teaching professionalism, which are VP dramatic
structure and how it should end. CONCLUSION: VPs intended for teaching
professionalism need to have high fidelity, follow a specific dramatic structure
and should include multiple plausible endings. The use of VPs as part of a
collaborative activity that is followed by a reflection session is perceived as
an effective tool for the development of ethical reasoning skills in dental
education.
PMID- 28691268
TI - Water availability affects seasonal CO2 -induced photosynthetic enhancement in
herbaceous species in a periodically dry woodland.
AB - Elevated atmospheric CO2 (eCO2 ) is expected to reduce the impacts of drought and
increase photosynthetic rates via two key mechanisms: first, through decreased
stomatal conductance (gs ) and increased soil water content (VSWC ) and second,
through increased leaf internal CO2 (Ci ) and decreased stomatal limitations
(Slim ). It is unclear if such findings from temperate grassland studies
similarly pertain to warmer ecosystems with periodic water deficits. We tested
these mechanisms in three important C3 herbaceous species in a periodically dry
Eucalyptus woodland and investigated how eCO2 -induced photosynthetic enhancement
varied with seasonal water availability, over a 3 year period. Leaf
photosynthesis increased by 10%-50% with a 150 MUmol mol-1 increase in
atmospheric CO2 across seasons. This eCO2 -induced increase in photosynthesis was
a function of seasonal water availability, given by recent precipitation and mean
daily VSWC . The highest photosynthetic enhancement by eCO2 (>30%) was observed
during the most water-limited period, for example, with VSWC <0.07 in this sandy
surface soil. Under eCO2 there was neither a significant decrease in gs in the
three herbaceous species, nor increases in VSWC , indicating no "water-savings
effect" of eCO2 . Periods of low VSWC showed lower gs (less than ~ 0.12 mol m-2
s-1 ), higher relative Slim (>30%) and decreased Ci under the ambient CO2
concentration (aCO2 ), with leaf photosynthesis strongly carboxylation-limited.
The alleviation of Slim by eCO2 was facilitated by increasing Ci , thus yielding
a larger photosynthetic enhancement during dry periods. We demonstrated that
water availability, but not eCO2 , controls gs and hence the magnitude of
photosynthetic enhancement in the understory herbaceous plants. Thus, eCO2 has
the potential to alter vegetation functioning in a periodically dry woodland
understory through changes in stomatal limitation to photosynthesis, not by the
"water-savings effect" usually invoked in grasslands.
PMID- 28691269
TI - The Effect of Intraoperative Systemic Lidocaine on Postoperative Persistent Pain
Using Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials
Criteria Assessment Following Breast Cancer Surgery: A Randomized, Double-Blind,
Placebo-Controlled Trial.
AB - OBJECTIVE: To compare the incidence in postsurgical persistent pain following
breast cancer surgery in women receiving intravenous lidocaine compared to saline
using validated pain instruments in accordance with the Initiative on Methods,
Measurement, and Pain Assessment in Clinical Trials (IMMPACT) recommendations.
METHODS: The study was a randomized, double-blinded, placebo-controlled, clinical
trial. Subjects were randomized into Group 1 (1.5 mg/kg bolus of intravenous
lidocaine followed by a 2 mg/kg/hour infusion) or Group 2 (normal saline at the
same bolus and infusion rate). Patients were evaluated at 3 and 6 months for the
presence of chronic persistent postsurgical pain. RESULTS: One hundred forty
eight patients were included in the study analysis. There were no differences in
quality of recovery, pain burden, or opioid consumption between groups at 24
hours. Pain (yes/no) at 6 months attributed to surgery was reported in 29% of
Group 2 vs. 13% of Group 1 patients (P = 0.04); however, only 3 subjects (5%) in
Group 1 and 2 subjects (3%) in Group 2 met IMMPACT criteria for persistent
postoperative pain (P = 0.99). DISCUSSION: Perioperative infusion of lidocaine
has been reported to decrease the incidence of postsurgical pain at 3 and 6
months following mastectomy using dichotomous (yes/no) scoring. Although
intravenous lidocaine reduced the reported incidence of pain at rest at 6 months,
pain with activity, pain qualities, and the physical or emotional impact of the
pain were unaffected. Future studies evaluating postsurgical persistent pain
should adhere to the IMMPACT recommendations in order to more accurately describe
the effect of an intervention on persistent pain.
PMID- 28691271
TI - Commentary on Laude et al. (2017): Extended treatment for cigarette smoking
cessation.
PMID- 28691272
TI - Commentary on Blow et al. (2017): Leveraging technology may boost the
effectiveness and adoption of interventions for drug use in emergency
departments.
PMID- 28691273
TI - Commentary on Marsden et al. (2017): While epidemiological studies can help to
identify areas of overdose risk, we need more focused hypothesis-driven trials to
inform clinical intervention strategies.
PMID- 28691274
TI - Commentary on Holst et al. (2017): The relationship between alcohol dependence
and risk of somatic diseases and mortality-the black box strikes back.
PMID- 28691275
TI - Commentary on McFall et al. (2017): The need for harm reduction interventions
that are effective for women who use drugs.
PMID- 28691276
TI - Diffusion of Carbon Dioxide and Nitrogen in the Small-Pore Titanium
Bis(phosphonate) Metal-Organic Framework MIL-91 (Ti): A Combination of
Quasielastic Neutron Scattering Measurements and Molecular Dynamics Simulations.
AB - The diffusivity of CO2 and N2 in the small-pore titanium-based bis(phosphonate)
metal-organic framework MIL-91(Ti) was explored by using a combination of
quasielastic neutron scattering measurements and molecular dynamics simulations.
These two techniques were used to determine the loading dependence of the self
diffusivity, corrected and transport diffusivities of these two gases to
complement our previously reported thermodynamics study, which revealed that this
material was a promising candidate for CO2 /N2 separation. The calculated and
measured diffusivities of both gases were shown to be of an order of magnitude
sufficiently high, from 10-9 to 10-10 m2 s-1 , and N2 diffused faster than CO2
through the small channel of MIL-91(Ti). Consequently, the separation process
does not involve any kinetic-driven limitations. This study further revealed that
the global diffusion mechanism involves motions of gases along the channels by a
jump sequence, and the residence times for CO2 in the region close to the
specific PO???H???N zwitterionic sites are much higher than those for N2 , which
explains the faster diffusivity observed for N2 .
PMID- 28691277
TI - Crotalus atrox Venom Exposed to Carbon Monoxide Has Decreased Fibrinogenolytic
Activity In Vivo in Rabbits.
AB - Envenomation by haemotoxic enzymes remains a significant source of human
morbidity and mortality worldwide, with administration of long-acting or multiple
doses of antivenom first-line therapy. However, coagulopathy can still occur and
recur. Of interest, it has been recently demonstrated that direct, isolated
exposure of snake venom enzymes with fibrinogenolytic activity to carbon monoxide
(CO) abrogates venom-mediated loss of coagulation in human plasma. These
observations of CO inhibition of venom fibrinogenolytic activity were
subsequently repeated in rabbit whole blood. This study sought to translate these
findings in an in vivo rabbit model of envenomation with fibrinogenolytic
Crotalus atrox venom. Sedated rabbits were intravenously administered C. atrox
venom (400 MUg/kg) pre-exposed to 0 or 1000 MUM carbon monoxide-releasing
molecule-2 (CORM-2) in vitro. Arterial whole-blood samples demonstrated that
compared to pre-envenomation values, the CORM-2-naive venom significantly
prolonged the onset of coagulation, decreased the velocity of clot growth and
decreased clot strength as determined by thromboelastography an hour after venom
injection. In contrast, CORM-2 pre-exposure prevented or attenuated C. atrox
venom effects on coagulation kinetics. Future studies to determine whether
rabbits injected with such venom subcutaneously/intramuscularly can have
consequent coagulopathy abrogated by injection of carbon monoxide-releasing
molecules into the 'bite site' are justified.
PMID- 28691278
TI - Cognitive function, treatment response to lithium, and social functioning in
Japanese patients with bipolar disorder.
AB - OBJECTIVES: Patients with bipolar disorder often suffer from cognitive impairment
that significantly influences their functional outcome. However, it remains
unknown whether lithium has a central role in cognition and functional outcome.
We examined whether cognition and functional outcome were predicted by
demographic and clinical variables, including the response to lithium, in lithium
treated patients with bipolar disorder. METHODS: We evaluated 96 lithium-treated
euthymic patients with bipolar disorder and 196 age- and-gender-matched healthy
controls, using the Brief Assessment of Cognition in Schizophrenia (BACS). The
patients were also assessed using the Social Functioning Scale (SFS) and "The
Retrospective Criteria of Long-Term Treatment Response in Research Subjects with
Bipolar Disorder" (Alda) scale, which was evaluated as either a continuous
measure of the total scale or a dichotomous criterion. RESULTS: Multiple
regression analysis revealed two key findings: first, that the premorbid
intelligence quotient, age, and number of mood episodes were predictors of the
BACS composite score; and, second, that the BACS composite score, negative
symptoms, and continuous measure on the total Alda scale (but not its dichotomy)
predicted the total SFS score. Structural equation modeling (SEM) was used to
confirm these findings, and additionally revealed that the Alda scale was
significantly associated with negative symptoms and also the number of mood
episodes, regardless of how it was evaluated. CONCLUSIONS: SEM delineated how
demographic and clinical variables, cognitive performance, and response to
lithium treatment were causally associated with, and converged on, social
function. The putative role of the Alda scale for social function warrants
further study.
PMID- 28691279
TI - Paleoecology of Neoproterozoic hypersaline environments: Biomarker evidence for
haloarchaea, methanogens, and cyanobacteria.
AB - While numerous studies have examined modern hypersaline ecosystems, their
equivalents in the geologic past, particularly in the Precambrian, are poorly
understood. In this study, biomarkers from ~820 million year (Ma)-old evaporites
from the Gillen Formation of the mid-Neoproterozoic Bitter Springs Group, central
Australia, are investigated to elucidate the antiquity and paleoecology of
halophiles. The sediments were composed of alternating laminae of dolomitized
microbial mats and up to 90% anhydrite. Solvent extraction of these samples
yielded thermally well-preserved hydrocarbon biomarkers. The regularly branched
C25 isoprenoid 2,6,10,14,18-pentamethylicosane, the tail-to-tail linked C30
isoprenoid squalane, and breakdown products of the head-to-head linked C40
isoprenoid biphytane, were particularly abundant in the most anhydrite-rich
sediments and mark the oldest current evidence for halophilic archaea. Linear
correlations between isoprenoid concentrations (normalized to n-alkanes) and the
anhydrite/dolomite ratio reveal microbial consortia that fluctuated with changing
salinity levels. Halophilic archaea were the dominant organisms during periods of
high salinity and gypsum precipitation, while bacteria were prevalent during
stages of carbonate formation. The irregularly branched C25 isoprenoid
2,6,10,15,19-pentamethylicosane (PMI), with a central tail-to-tail link, was also
abundant during periods of elevated salinity, highlighting the activity of
methanogens. By contrast, the irregularly branched C20 isoprenoid 2,6,11,15
tetramethylhexadecane (crocetane) was more common in dolomite-rich facies,
revealing that an alternate group of archaea was active during less saline
periods. Elevated concentrations of isotopically depleted heptadecane (n-C17 )
revealed the presence of cyanobacteria under all salinity regimes. The
combination of biomarkers in the mid-Neoproterozoic Gillen Formation resembles
lipid compositions from modern hypersaline cyanobacterial mats, pointing to a
community composition that remained broadly constant since at least the
Neoproterozoic. However, as a major contrast to most modern hypersaline
environments, the Gillen evaporites did not yield any evidence for algae or other
eukaryotes.
PMID- 28691280
TI - XXV Biennial Meeting of the International Perinatal Collegium, Edinburgh,
Scotland, 2-6 July 2017.
PMID- 28691281
TI - Extreme population-level events: Do they have an impact on cancer?
PMID- 28691282
TI - Phytochemical Composition and Antioxidant Activities of the Essential Oil and
Extracts of Satureja subspicata Vis. Growing in Bosnia and Herzegovina.
AB - The phytochemical composition and the antioxidant activities of the essential
oil, as well as methanol and hot water extracts of endemic Satureja subspicata
Vis. growing in Bosnia and Herzegovina (BiH), were described. beta-Caryophyllene,
cis-beta-ocimene, and alpha-pinene, identified by GC/MS and GC-FID, were the
dominant oil components. The major compound of both of extracts, identified by
HPLC-DAD, was rosmarinic acid. The analyzed essential oil showed moderate
antioxidant activity. In this first report on the extracts of S. subspicata
growing in BiH, the obtained results showed a high content of rosmarinic acid, as
well as considerable amount of total phenols and flavonoids. Compared to the hot
water extract, the methanol extract exhibits higher antioxidant potential,
measured by DPPH and FRAP assay (IC50 = 0.45 g/l and 1879.43 equiv. Fe2+ MUm),
while the hot water extract showed higher potential in inhibition of linoleic
acid oxidation (51.7% and 61.5% for 1 and 10 g/l). A good antioxidant potential
of the tested extracts indicates their potential use as antioxidants,
particularly for lipid protection, and partly explains the justification of the
use of this plant in traditional medicine of BiH.
PMID- 28691283
TI - A Soft Total Artificial Heart-First Concept Evaluation on a Hybrid Mock
Circulation.
AB - The technology of 3D-printing has allowed the production of entirely soft pumps
with complex chamber geometries. We used this technique to develop a completely
soft pneumatically driven total artificial heart from silicone elastomers and
evaluated its performance on a hybrid mock circulation. The goal of this study is
to present an innovative concept of a soft total artificial heart (sTAH). Using
the form of a human heart, we designed a sTAH, which consists of only two
ventricles and produced it using a 3D-printing, lost-wax casting technique. The
diastolic properties of the sTAH were defined and the performance of the sTAH was
evaluated on a hybrid mock circulation under various physiological conditions.
The sTAH achieved a blood flow of 2.2 L/min against a systemic vascular
resistance of 1.11 mm Hg s/mL (afterload), when operated at 80 bpm. At the same
time, the mean pulmonary venous pressure (preload) was fixed at 10 mm Hg.
Furthermore, an aortic pulse pressure of 35 mm Hg was measured, with a mean
aortic pressure of 48 mm Hg. The sTAH generated physiologically shaped signals of
blood flow and pressures by mimicking the movement of a real heart. The
preliminary results of this study show a promising potential of the soft pumps in
heart replacements. Further work, focused on increasing blood flow and in turn
aortic pressure is required.
PMID- 28691285
TI - Phenotyping asthma: More complex than just age.
PMID- 28691284
TI - Performance characteristics of serum C4 and FGF19 measurements to exclude the
diagnosis of bile acid diarrhoea in IBS-diarrhoea and functional diarrhoea.
AB - BACKGROUND: The serum biomarkers, elevated 7alphaC4 (C4) and decreased FGF19,
have been proposed as screening tests for bile acid diarrhoea. AIM: To analyse
prevalence, specificity and reproducibility of fasting C4 and FGF19 in
identifying bile acid diarrhoea in patients with irritable bowel syndrome with
predominant diarrhoea or functional diarrhoea (summarised as IBS-D). METHODS: We
prospectively studied fasting serum C4 and FGF19 in 101 IBS-D patients; we
reviewed data from 37 of the 101 patients with prior fasting serum C4 and FGF19
and from 30 of the 101 patients with prior faecal bile acids per 48 hours. We
compared results with normal values (C4 >=52.5 ng/mL [n=184], FGF-19 <=61.7 pg/mL
[n=50]). We used Spearman correlation and Bland-Altman plots to appraise
reproducibility. RESULTS: Among the 101 patients, there was a negative
correlation between serum C4 and FGF19 (Rs=-.342, P=.0005). Bile acid diarrhoea
was diagnosed in 10 patients based on elevated serum C4 levels (mean 23.5+/-23.1
[SD] ng/mL) and 21 patients based on decreased FGF19 levels (121.6+/-84.2 pg/mL).
With replicate tests in patients with stable IBS-D, 78% of C4 and 70% of FGF19
measurements remained concordant, with 3% and 11% respectively consistently
positive for bile acid diarrhoea in the 101 patients. Compared to 48 hours faecal
bile acids, specificity for C4 and FGF19 was 83% and 78%, respectively. Bland
Altman plots demonstrated greater reliability of C4 than FGF19. CONCLUSIONS:
Among 101 patents with IBS-D, fasting FGF19 and C4 levels had good specificity
and negative predictive value, suggesting utility as screening tests to exclude
bile acid diarrhoea.
PMID- 28691286
TI - Prominent Electron Penetration through Ultrathin Graphene Layer from FeNi Alloy
for Efficient Reduction of CO2 to CO.
AB - The chemical transformation of CO2 is an efficient approach in low-carbon energy
system. The development of nonprecious metal catalysts with sufficient activity,
selectivity, and stability for the generation of CO by CO2 reduction under mild
conditions remains a major challenge. A hierarchical architecture catalyst
composed of ultrathin graphene shells (2-4 layers) encapsulating homogeneous FeNi
alloy nanoparticles shows enhance catalytic performance. Electron transfer from
the encapsulated alloy can extend from the inner to the outer shell, resulting in
an increased charge density on graphene. Nitrogen atom dopants can
synergistically increase the electron density on the catalyst surface and
modulate the adsorption capability for acidic CO2 molecules. The optimized FeNi3
@NG (NG=N-doped graphene) catalyst, with significant electron penetration through
the graphene layer, effects exceptional CO2 conversion of 20.2 % with a CO
selectivity of nearly 100 %, as well as excellent thermal stability at 523 K.
PMID- 28691295
TI - National Speakers.
PMID- 28691287
TI - Effects of iodine methionine on boar sperm quality during liquid storage at 17
degrees C.
AB - Microbial environment is one of the important factors that affect the quality of
preserved semen. Iodine methionine (IM), participating in the production and
activation of metabolic enzymes, is a new type of amino acid chelate. To date,
there has been no report to evaluate the effects of IM on boar semen preservation
at 17 degrees C. This study was designed to investigate the effects of IM on boar
sperm quality and reproductive performance during liquid storage at 17 degrees C
and its antibacterial effect. Semen samples collected from six Yorkshire boars
were diluted with basic liquid containing different concentrations of IM (0, 20,
40, 80, 160 and 320 MUM). Subsequently, sperm motility, plasma membrane integrity
and acrosome integrity were determined. After 6 days of preservation, the
difference in microbial composition between control group and 80 MUM IM group was
compared using 16S rDNA sequencing, and the effects of IM on reproductive
performance were also compared and analysed between the two groups. The results
demonstrated that 20, 40 and 80 MUM IM improved boar sperm motility, plasma
membrane integrity and acrosome integrity. 80 MUM IM was the optimum
concentration. Conversely, 160 and 320 MUM IM resulted in deleterious
consequences to boar sperm quality compared to the control group and other
treatment groups (p < .05). After 6 days of preservation, sperm motility, plasma
membrane integrity and acrosome integrity were 56.0%, 51.8% and 59.4%,
respectively. There was no significant difference in non-return rate between the
two groups (p > .05). But the litter size of 80 MUM IM group was significantly
higher than that of control group (p < .05). 80 MUM IM inhibited proliferation of
the phylum Proteobacteria and the genus Staphylococcus as well as Pseudomonas (p
< .05). Further studies are required to understand the antibacterial mechanism of
IM in liquid-preserved boar semen.
PMID- 28691302
TI - Identification of a novel HLA-A allele, HLA-A*02:315.
AB - HLA-A*02:315 differs from A*02:03:01 by one nucleotide change at position 241
from C to T.
PMID- 28691303
TI - Acquired reactive perforating collagenosis associated with Hodgkin disease.
PMID- 28691304
TI - Pharmacophore feature prediction and molecular docking approach to identify novel
anti-HCV protease inhibitors.
AB - Discovering a potential drug for HCV treatment is a challenging task in the field
of drug research. This study initiates with computational screening and modeling
of promising ligand molecules. The foremost modeling method involves the
identification of novel compound and its molecular interaction based on
pharmacophore features. A total of 197 HCV compounds for NS3/4A protein target
were screened for our study. The pharmacophore models were generated using PHASE
module implemented in Schrodinger suite. The pharmacophore features include one
hydrogen bond acceptor, one hydrogen bond donor, and three hydrophobic sites. As
a result, based on mentioned hypothesis the model ADHHH.159 corresponds to the
CID 59533233. Furthermore, docking was performed using maestro for all the 197
compounds. Among these, the CID 59533313 and 59533233 possess the best binding
energy of -11.75 and -10.40 kcal/mol, respectively. The interactions studies
indicated that the CID complexed with the NS3/4A protein possess better binding
affinity with the other compounds. Further the compounds were subjected to
calculate the ADME properties. Therefore, it can be concluded that these two
compounds could be a potential alternative drug for the development of HCV.
PMID- 28691305
TI - A comparison of methods for inferring causal relationships between genotype and
phenotype using additional biological measurements.
AB - Genome wide association studies (GWAS) have been very successful over the last
decade at identifying genetic variants associated with disease phenotypes.
However, interpretation of the results obtained can be challenging. Incorporation
of further relevant biological measurements (e.g. 'omics' data) measured in the
same individuals for whom we have genotype and phenotype data may help us to
learn more about the mechanism and pathways through which causal genetic variants
affect disease. We review various methods for causal inference that can be used
for assessing the relationships between genetic variables, other biological
measures, and phenotypic outcome, and present a simulation study assessing the
performance of the methods under different conditions. In general, the methods we
considered did well at inferring the causal structure for data simulated under
simple scenarios. However, the presence of an unknown and unmeasured common
environmental effect could lead to spurious inferences, with the methods we
considered displaying varying degrees of robustness to this confounder. The use
of causal inference techniques to integrate omics and GWAS data has the potential
to improve biological understanding of the pathways leading to disease. Our study
demonstrates the suitability of various methods for performing causal inference
under several biologically plausible scenarios.
PMID- 28691306
TI - To define melancholia, follow the path of catatonia.
PMID- 28691307
TI - Socio-sexual functioning in autism spectrum disorder: A systematic review and
meta-analyses of existing literature.
AB - : Socio-sexual functioning encompasses an individual's interests, behaviors, and
knowledge with respect to sexual, romantic, and social aspects of life. An
individual's understanding of these domains is developed through a range of
informal and formal avenues of sexual health education. The current model
demonstrated this and proposed that, compared to typically developing
individuals, those with ASD develop socio-sexual functioning differently due to
having less peer engagement, less relationship experience, more parental
guidance, greater use of online materials, receive less school-based sexual
health education, and more support from wellbeing services. Systematic review and
meta-analysis of existing literature revealed that individuals with ASD have
greater difficultly adhering to privacy norms, engage in less social behavior,
are described as engaging in less appropriate sexual behavior, have greater
concerns about themselves, and receive less sexual health education. Having fewer
opportunities for appropriate informal and formal sexual health education leaves
them at a double disadvantage from others who are receiving this information from
both of these avenues. Some of the current meta-analytic results are cautioned by
large l-square statistics which suggest that a degree of variance is being caused
by extraneous factors. Further empirical research in this area is needed to
overcome current design and sample limitations. Finally, the Sexual Behavior
Scale was the most commonly utilized tool in the meta-analyzed studies, thus
comprehensive evaluation of its functioning is warranted. The importance of work
in this area is highlighted by the central role of social and sexual wellbeing on
one's quality of life. Autism Res 2017, 10: 1823-1833. (c) 2017 International
Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Review of
existing literature revealed that individuals with ASD have greater difficultly
adhering to privacy norms, engage in less social behavior, are described as
engaging in less appropriate sexual behavior, have greater concerns about
themselves, and receive less sexual health education. Having fewer opportunities
for appropriate informal and formal sexual health education leaves them at a
double disadvantage from others who are receiving this information from both of
these avenues.
PMID- 28691308
TI - Assessment of hypertensive cerebrovascular alterations with multiband Look-Locker
arterial spin labeling.
AB - PURPOSE: To quantitatively assess the hypertension-induced cerebrovascular
alterations by measuring the dynamics of arterial spin labeling (ASL) signals.
MATERIALS AND METHODS: The multiband Look-Locker ASL (MB LL-ASL) technique was
evaluated in comparison to a single-band LL-ASL for three healthy subjects. Also,
seven healthy subjects were scanned to determine the strength of the vascular
crushing gradients applied to separate arterial from tissue ASL signal. With the
optimized MB LL-ASL technique, multiple parameters, cerebral blood flow (CBF),
transit times to artery (tA ), and capillary (tC ), delivery duration of labeled
blood (tau), and arterial blood volume (CBVa ), were simultaneously quantified
for age-matched eight control and eight hypertensive subjects with 259 msec of
temporal resolution and 20 slices covering the whole-brain region at 3T. RESULTS:
While CBF of hypertensives were comparable with those of normotensives (CBF of
normotensives vs. hypertensives = 62.2 +/- 6.87 vs. 61.9 +/- 8.94 ml/100g/min, P
= 0.960 for the whole gray matter), tC and tau were prolonged in hypertensives in
most brain regions (tC = 1.30 +/- 0.09 vs. 1.76 +/- 0.16 sec, P = 0.034; tau =
1.46 +/- 0.10 vs. 2.30 +/- 0.22 sec, P = 0.006 for the whole gray matter). Two
regions showed the increased CBVa in hypertensives compared to normotensives
(hippocampus and thalamus with P = 0.009 and 0.035, respectively). CONCLUSION:
Hypertension slows the perfusion dynamics, while the remaining CBF is unchanged.
A detailed characterization of regional cerebrovascular impairments by MB-LL-ASL
technique provides better understanding of hypertension-induced cerebrovascular
modifications. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. Magn. Reson.
Imaging 2018;47:663-672.
PMID- 28691309
TI - Serial D-dimer plasma levels in a patient with chronic spontaneous urticaria
developing resistance to omalizumab.
AB - Chronic spontaneous urticaria (CSU) is a condition presenting as the spontaneous
occurrence of itchy weals with or without angio-oedema for > 6 weeks. A patient
with severe chronic spontaneous urticaria who developed resistance to omalizumab
is described. The patient's D-dimer plasma levels strictly paralleled the disease
activity despite the administration of anti-IgE therapy.
PMID- 28691310
TI - Solution Combustion Synthesis: Low-Temperature Processing for p-Type Cu:NiO Thin
Films for Transparent Electronics.
AB - Low-temperature solution processing opens a new window for the fabrication of
oxide semiconductors due to its simple, low cost, and large-area uniformity.
Herein, by using solution combustion synthesis (SCS), p-type Cu-doped NiO
(Cu:NiO) thin films are fabricated at a temperature lower than 150 degrees C.
The light doping of Cu substitutes the Ni site and disperses the valence band of
the NiO matrix, leading to an enhanced p-type conductivity. Their integration
into thin-film transistors (TFTs) demonstrates typical p-type semiconducting
behavior. The optimized Cu5% NiO TFT exhibits outstanding electrical performance
with a hole mobility of 1.5 cm2 V-1 s-1 , a large on/off current ratio of ~104 ,
and clear switching characteristics under dynamic measurements. The employment of
a high-k ZrO2 gate dielectric enables a low operating voltage (<=2 V) of the
TFTs, which is critical for portable and battery-driven devices. The construction
of a light-emitting-diode driving circuit demonstrates the high current control
capability of the resultant TFTs. The achievement of the low-temperature
processed Cu:NiO thin films via SCS not only provides a feasible approach for low
cost flexible p-type oxide electronics but also represents a significant step
toward the development of complementary metal-oxide semiconductor circuits.
PMID- 28691311
TI - Bayesian adaptive dose-escalation designs for simultaneously estimating the
optimal and maximum safe dose based on safety and efficacy.
AB - The main purpose of dose-escalation trials is to identify the dose(s) that is/are
safe and efficacious for further investigations in later studies. In this paper,
we introduce dose-escalation designs that incorporate both the dose-limiting
events and dose-limiting toxicities (DLTs) and indicative responses of efficacy
into the procedure. A flexible nonparametric model is used for modelling the
continuous efficacy responses while a logistic model is used for the binary DLTs.
Escalation decisions are based on the combination of the probabilities of DLTs
and expected efficacy through a gain function. On the basis of this setup, we
then introduce 2 types of Bayesian adaptive dose-escalation strategies. The first
type of procedures, called "single objective," aims to identify and recommend a
single dose, either the maximum tolerated dose, the highest dose that is
considered as safe, or the optimal dose, a safe dose that gives optimum benefit
risk. The second type, called "dual objective," aims to jointly estimate both the
maximum tolerated dose and the optimal dose accurately. The recommended doses
obtained under these dose-escalation procedures provide information about the
safety and efficacy profile of the novel drug to facilitate later studies. We
evaluate different strategies via simulations based on an example constructed
from a real trial on patients with type 2 diabetes, and the use of stopping rules
is assessed. We find that the nonparametric model estimates the efficacy
responses well for different underlying true shapes. The dual-objective designs
give better results in terms of identifying the 2 real target doses compared to
the single-objective designs.
PMID- 28691312
TI - Paraoxonase 1 (PON1) activity in serum, follicular fluid and seminal plasma of
sheep.
AB - This work aimed to describe the activity of paraoxonase 1 (PON1) in serum,
follicular fluid and seminal plasma of sheep. Average serum PON1 activity was
286.8 +/- 96.2 U/ml in females and 237.6 +/- 18.9 U/ml in males. There was a
positive correlation between PON1 activity in serum and follicular fluid in
females, being twice higher in serum than in follicular fluid (148.8 +/- 15.7
U/ml). PON1 activity in males' serum was 10-fold higher than in seminal plasma
(21.18 +/- 14.2 U/ml), and there was no correlation between PON1 activity in both
compartments. Finally, this work suggests that PON1 activity of in sheep is
higher compared to other mammalian species, and there is an association between
PON1 in serum and follicular fluid only.
PMID- 28691313
TI - Moderate mammalian target of rapamycin inhibition induces autophagy in HTR8/SVneo
cells via O-linked beta-N-acetylglucosamine signaling.
AB - AIM: Autophagy, a highly regulated process with a dual role (pro-survival or pro
death), has been implicated in adverse pregnancy outcomes. The aim of this study
was to explore the mechanism whereby mammalian target of rapamycin (mTOR)
signaling regulates autophagy by modulating protein O-GlcNAcylation in human
trophoblasts. METHODS: HTR8/SVneo cells were incubated in serum-free medium for
different time intervals or treated with varying doses of Torin1. Protein
expression and cell apoptosis were detected by immunoblotting and flow cytometry,
respectively. RESULTS: Short-term serum starvation or slight suppression of mTOR
signaling promoted autophagy and decreased apoptosis in HTR8/SVneo cells.
Conversely, prolonged serum starvation or excessive inhibition of mTOR reduced
autophagy and enhanced cell apoptosis. Both serum starvation and mTOR signaling
suppression reduced protein O-GlcNAcylation. Upregulation and downregulation of O
linked beta-N-acetylglucosamine (O-GlcNAc) levels attenuated and augmented
autophagy, respectively. Moderate mTOR inhibition-induced autophagy was blocked
by upregulation of protein O-GlcNAcylation. Furthermore, immunoprecipitation
studies revealed that Beclin1 and synaptosome associated protein 29 (SNAP29)
could be O-GlcNAcylated, and that slight mTOR inhibition resulted in decreased O
GlcNAc modification of Beclin1 and SNAP29. Notably, we observed an inverse
correlation between phosphorylation (Ser15) and O-GlcNAcylation of Beclin1.
CONCLUSION: mTOR signaling inhibition played dual roles in regulating autophagy
and apoptosis in HTR8/SVneo cells. Moderate mTOR suppression might induce
autophagy via modulating O-GlcNAcylation of Beclin1 and SNAP29. Moreover, the
negative interplay between Beclin1 O-GlcNAcylation and phosphorylation (Ser15)
may be involved in autophagy regulation by mTOR signaling.
PMID- 28691314
TI - Sonographic Findings of Endometrial Osseous Metaplasia, a Cause of Dysfunctional
Vaginal Bleeding and Secondary Infertility.
PMID- 28691315
TI - Metal-Folded Single-Chain Nanoparticle: Nanoclusters and Self-Assembled Reduction
Responsive Sub-5-nm Discrete Subdomains.
AB - Easy access to discrete nanoclusters in metal-folded single-chain nanoparticles
(metal-SCNPs) and independent ultrafine sudomains in the assemblies via
coordination-driven self-assembly of hydrophilic copolymer containing 9%
imidazole groups is reported herein. 1 H NMR, dynamic light scattering, and NMR
diffusion-ordered spectroscopy results demonstrate self-assembly into metal-SCNPs
(>70% imidazole-units folded) by neutralization in the presence of Cu(II) in
water to pH 4.6. Further neutralization induces self-assembly of metal-SCNPs (pH
4.6-5.0) and shrinkage (pH 5.0-5.6), with concurrent restraining residual
imidazole motifs and hydrophilic segment, which organized into constant
nanoparticles over pH 5.6-7.5. Atomic force microscopy results evidence discrete
1.2 nm nanoclusters and sub-5-nm subdomains in metal-SCNP and assembled
nanoparticle. Reduction of metal center using sodium ascorbate induces structural
rearrangement to one order lower than the precursor. Enzyme mimic catalysis
required media-tunable discrete ultrafine interiors in metal-SCNPs and assemblies
have hence been achieved.
PMID- 28691316
TI - Efficacy of an unwaxed dental floss impregnated with 2% chlorhexidine on control
of supragingival biofilm: A randomized, clinical trial.
AB - AIM: In the present study, we evaluated the antiplaque and antigingivitis
efficacy of a dental floss impregnated with 2% chlorhexidine digluconate.
METHODS: Thirty dental students were randomly divided into three groups (n=10):
(a) negative control (NC) group, in which no interproximal cleaning was
performed; (b) the positive control (PC) group, which used a standard unwaxed
dental floss twice daily; and (c) and the test group, which used a unwaxed dental
floss impregnated with 2% chlorhexidine twice daily. Six surfaces per tooth were
evaluated by the Quigley-Hein plaque index (Turesky modification) at the last
appointment (day 15), and testing for the presence of marginal bleeding was
performed using the marginal bleeding index (MBI) at both the baseline and last
appointments. RESULTS: At day 15, the test group had the lowest mean plaque index
(1.04+/-0.67), showing a statistically-significant difference compared to the NC
group (1.40+/-0.65, P<.001) and PC group (2.30+/-0.73, P<.001). The PC and test
groups showed a mean reduction of 70.2% and 87.26%, respectively, with
significant reduction compared to baseline (P<.05) for the MBI. No statistically
significant difference was found between the PC and test groups (P=.126).
CONCLUSION: Unwaxed dental floss impregnated with 2% chlorhexidine showed
additional reductions in supragingival interproximal biofilm compared with a
conventional unwaxed dental floss, without additional improvement in marginal
bleeding.
PMID- 28691317
TI - Synthesis and Characterization of a Novel Microporous Dihydroxyl-Functionalized
Triptycene-Diamine-Based Polyimide for Natural Gas Membrane Separation.
AB - An intrinsically microporous polyimide is synthesized in m-cresol by a one-pot
high-temperature condensation reaction of 4,4'
(hexafluoroisopropylidene)diphthalic anhydride (6FDA) and newly designed 2,6 (7)
dihydroxy-3,7(6)-diaminotriptycene (DAT1-OH). The 6FDA-DAT1-OH polyimide is
thermally stable up to 440 degrees C, shows excellent solubility in polar
solvents, and has moderately high Brunauer-Teller-Emmett (BET) surface area of
160 m2 g-1 , as determined by nitrogen adsorption at -196 degrees C. Hydroxyl
functionalization applied to the rigid 3D triptycene-based diamine building block
results in a polyimide that exhibits moderate pure-gas CO2 permeability of 70
Barrer combined with high CO2 /CH4 selectivity of 50. Mixed-gas permeation
studies demonstrate excellent plasticization resistance of 6FDA-DAT1-OH with
impressive performance as potential membrane material for natural gas sweetening
with a CO2 permeability of 50 Barrer and CO2 /CH4 selectivity of 40 at a typical
natural gas well partial pressure of 10 atm.
PMID- 28691318
TI - A rare cause of alopecia: Lipedematous alopecia.
PMID- 28691319
TI - Fitness plus American Society of Anesthesiologists grade improve outcome
prediction after endovascular aneurysm repair.
AB - BACKGROUND: Although the American Society of Anesthesiologists (ASA) grade was
established for statistical purposes, it is often used prognostically. However,
older patients undergoing elective surgery are typically ASA III, which limits
patient stratification. We look at the prognostic effect on early complications
and survival of using ASA and self-reported physical fitness to stratify patients
undergoing endovascular repair of abdominal aortic aneurysms. METHODS: Data were
extracted from a trial database. All patients were assigned a fitness level (A
(fit) or B (unfit)) based on their self-reported ability to walk briskly for 1 km
or climb two flights of stairs. Fitness was used to stratify ASA III patients,
with fitter patients assigned ASA IIIA and less fit patients ASA IIIB. Outcomes
assessed included survival, reinterventions, endoleak, all early and late
complications and early operative complications. RESULTS: A combined ASA/fitness
scale (II, IIIA, IIIB and IV) correlated with 1- and 3-year survival (1-year P =
0.001, 3-year P = 0.001) and early and late complications (P = 0.001 and P =
0.05). On its own, ASA predicted early complications (P = 0.0004) and survival (1
year P = 0.01, 3-year P = 0.01). Fitness alone was predictive for survival (1
year P = 0.001, 3-year P = 0.001) and late complications (P = 0.009). CONCLUSION:
This study shows that even a superficial assessment of fitness is reflected in
surgical outcomes, with fitter ASA III patients showing survival patterns similar
to ASA II patients. Physicians should be alert to differences in fitness between
patients in the ASA III group, despite similarities based on preexisting severe
systemic disease.
PMID- 28691320
TI - Use of ultrasound shear-wave elastography to evaluate change in cervical
stiffness during pregnancy.
AB - AIM: The aim of this study was to evaluate the usefulness of shear-wave
elastography (SWE) for measuring change in cervical stiffness during pregnancy,
with regions of interest (ROI) designed for easy identification. METHODS: A total
of 280 women were enrolled in this study. SWE was performed at a routine prenatal
visit. A measurement area was chosen at the anterior part of the cervix, and a
circular ROI 5 mm in diameter was set at two points, 5-10 mm (lower point) and 15
20 mm (upper point) from the external cervical os. The generalized estimating
equation was used to estimate the correlation between stiffness and gestational
age, using generalized linear models. RESULTS: There were significant negative
correlations between stiffness and gestational age. The estimated regression
equations of the lower and upper points were Y = -0.049X + 3.675 (P < 0.05) and Y
= -0.060X + 4.170 (P < 0.05), respectively. The stiffness at the upper point
behaved statistically significantly differently to that at the lower point.
Softening of the cervix at the upper point was significantly different between
single pregnancies and twin pregnancies (P < 0.05), but no marked difference was
noted between primiparous and multiparous women. CONCLUSION: Cervical
elastography using SWE was useful for measuring change in cervical stiffness
during pregnancy, and the upper area of the cervix may be a more relevant
assessment point for cervical softening than the lower area.
PMID- 28691321
TI - Possible TRALI is a real entity.
AB - After the consensus definition of transfusion-related acute lung injury (TRALI),
studies have shown that the incidence of TRALI is high in critically ill and
injured patients. When another risk factor for lung injury is present in these
patients, the term "possible TRALI" is used. In the past years, both animal and
clinical studies have taught us that a predisposing inflammatory risk factor is
frequently present in TRALI, if not mandatory. The decline in the incidence of
TRALI after implementation of the use of male-only plasma as observed in general
hospital patients is also seen in the critically ill and injured, suggesting that
antibodies play a role in possible TRALI. Thereby, introduction of the term
"possible TRALI" has helped us in estimating incidence rates as well as to
understand risk factors for TRALI in patient populations with a high exposure to
transfusion.
PMID- 28691322
TI - Bile acid levels and risk of adverse perinatal outcomes in intrahepatic
cholestasis of pregnancy: A meta-analysis.
AB - AIM: We aimed to determine the association between maternal total bile acid (TBA)
levels and the risks of adverse perinatal outcomes in pregnant women with
intrahepatic cholestasis of pregnancy (ICP) based on a meta-analysis study.
METHODS: We searched PubMed for articles published from 2000 to 2015 with a focus
on ICP and restriction to the English language. The main perinatal outcomes were
preterm birth (PTB), meconium-stained amniotic fluid (MSAF), asphyxia, or
respiratory distress syndrome (RDS). Relative risk (RR) with 95% confidence
intervals (CI) was the summary statistic. We used a random- or fixed-effects
model to calculate the pooled RR according to the heterogeneity test. Subgroup
analyses were performed by region and study design. RESULTS: Nine eligible
related citations fulfilled the inclusion criteria and were included in this
study. Compared with pregnant women with a serum TBA < 40 MUmol/L, severe ICP
(TBA >= 40 MUmol/L) was associated with a significantly increased risk of adverse
fetal outcomes (pooled RR, 1.96; 95%CI, 1.63-2.35), PTB (pooled RR, 2.23; 95%CI,
1.51-3.29), MSAF (pooled RR, 2.27; 95%CI, 1.81-2.85), and asphyxia or RDS (pooled
RR, 1.67; 95%CI, 1.18-2.36). Sensitivity analysis suggested that the study design
difference may be a major source of heterogeneity. No publication bias was
demonstrated by Begg's test (P > 0.05). CONCLUSION: This meta-analysis indicates
that maternal elevated bile acid levels are significantly associated with
increased risks of overall adverse perinatal outcomes, PTB, MSAF, and asphyxia or
RDS. Serum TBA levels seem to be a useful predictor for the risk of adverse
perinatal outcomes.
PMID- 28691323
TI - Knowledge translation interventions to sustain direct care provider behaviour
change in long-term care: A process evaluation.
AB - RATIONALE, AIMS, AND OBJECTIVES: Process evaluation can be used to understand the
factors influencing the impact of knowledge translation (KT) interventions. The
aim of this mixed methods process evaluation was to evaluate the processes and
perceived outcomes of eight KT interventions that were used with healthcare aides
(HCAs) to introduce a mobility innovation into their daily care practices. The
study examined the perceived effectiveness of various KT interventions in
sustaining daily performance of the sit-to-stand mobility innovation by HCAs with
residents in long-term care. METHOD: In-person interviews were conducted with
four leaders across three long-term care facilities. Seven focus groups with 27
HCAs were conducted across the three facilities. All participants were asked to
rank the eight interventions involved in the trial according to their perceived
effectiveness and, for the leaders, their perceived ease of implementation. Focus
group and interview questions asked participants to discuss the relative merits
of each KT intervention. Two research assistants coded all of the transcripts
independently using content analysis. RESULTS: Both HCAs and their leaders
perceived reminders, followed by discussion groups, to be the most effective KT
interventions to sustain practice change. Healthcare aide champions were deemed
least effective by both leaders and HCAs. Leaders identified both the focus group
discussion and audit and feedback posters in the study as the most difficult to
implement. Participants valued interventions that were strategically visible,
helped to clarify misconceptions about the new care innovation, supported
teamwork, and made visible the resident benefits of the care innovation.
Logistical issues, such as staff scheduling and workload, influenced the
perceived feasibility of the various KT interventions. CONCLUSIONS: Understanding
how care staff in long-term care settings perceive KT interventions can inform
the choice of future use of these interventions to move research evidence into
practice.
PMID- 28691324
TI - Diagnostic Value of Contrast-Enhanced Ultrasonography and Time-Intensity Curve in
Differential Diagnosis of Cervical Metastatic and Tuberculous Lymph Nodes.
AB - OBJECTIVES: To evaluate the diagnostic value of contrast-enhanced ultrasonography
(CEUS) in the differential diagnosis of tuberculous and metastatic lymph nodes.
METHODS: Nineteen cervical tuberculous lymph nodes and 43 cervical metastatic
lymph nodes were investigated. The CEUS perfusion patterns and parameters of time
intensity curve (TIC) were analyzed. Diagnostic accuracy and consistency of two
physicians were compared before and after CEUS and TIC analysis. RESULTS:
Conventional ultrasonography showed no significant differences between
tuberculous and metastatic lymph nodes. Concentric enhancement at the arterial
phase of CEUS occurred in 15 of 19 (78.9%) tuberculous lymph nodes and 42 of 43
(97.7%) metastatic lymph nodes (P < .05). For the TIC curve, a steep descending
curve with an apparent notch was commonly found in tuberculous lymph nodes (13 of
16). Although a shallow descending curve was common (40 of 43) in metastatic
lymph nodes, most did not have a notch on the curve (39 of 43) (P < .01). The k
value and the peak intensity (PI) value of tuberculous lymph nodes were
significantly higher and the ?PI value was significantly lower than that of
metastatic lymph nodes (P < .05, respectively). Kappa values for the diagnosis
consistency of the two physicians before and after CEUS and TIC analysis were
0.582 and 0.761, respectively. Diagnostic accuracy before and after CEUS and TIC
analysis was 47.4% (28 of 59) and 96.6% (57 of 59), respectively (P < .001).
CONCLUSIONS: Contrast-enhanced ultrasonography with TIC analysis is helpful in
differentiating tuberculous from metastatic lymph nodes.
PMID- 28691325
TI - Cellular and extracellular vesicular origins of miRNAs within the bovine ovarian
follicle.
AB - The ovarian follicle components must provide an ideal environment to ensure the
success of reproductive processes, and communication between follicular cells is
crucial to support proper oocyte growth. Recently, it has been demonstrated that
the presence of extracellular vesicles (EVs) carrying microRNAs (miRNAs) in
follicular fluid represents an important autocrine and paracrine communication
mechanism inside the ovarian follicle. In this study, we tested the hypothesis
that the miRNA content of EVs isolated from ovarian follicular (granulosa and
cumulus-oocyte complexes) cell-conditioned culture media is dependent upon cell
type. We initially screened bovine granulosa cells (GCs) and cumulus-oocyte
complexes (COCs), as well as their derived EVs for 348 miRNAs using real-time
PCR, and detected 326 miRNAs in GCs and COCs cells and 62 miRNAs in GCs and COCs
EVs. A bioinformatics analysis of the identified cell-specific and differentially
expressed miRNAs predicted that they likely modulate important cellular
processes, including signalling pathways such as the PI3K-Akt, MAPK and Wnt
pathways. By investigating the origins of miRNAs within the follicular fluid, the
results of this study provide novel insights into follicular miRNA content and
intercellular communication that may be of invaluable use in the context of
reproductive technologies, diagnostic of ovarian-related diseases and/or the
identification of biomarkers for oocyte and embryo quality.
PMID- 28691326
TI - Total Synthesis of (+)-Dendrowardol C.
AB - The first total synthesis of the tetracyclic sesquiterpenoid (+)-dendrowardol C
is described. It relies on an intramolecular aldol reaction to forge the central
bicyclic scaffold and subsequent cyclobutane formation by cyclization of a gamma
triflyloxy ketone. Key is the treatment of the latter with lithium naphthalenide.
Finally, the diastereoselective hydroboration of a 1,1-disubstituted double bond
is enabled by a chiral CoI catalyst.
PMID- 28691327
TI - Ending cervical cancer: A call to action.
AB - The outlook for elimination of the scourge of cervical cancer is bright, because
we now have the tools to achieve this goal. In recent years human papillomavirus
(HPV) vaccination in high-income countries has resulted in dramatic decreases in
HPV infection and associated cervical disease. If all countries with a
substantial burden of disease introduce the vaccine nationally, we can protect
the vast majority of women and girls most at risk. For women who are beyond the
vaccination target age, progress has been made in screening and treatment for
cervical precancer, but we must accelerate this momentum to reduce incidence and
mortality worldwide to the very low rates found in wealthier countries. Human and
financial resources must be increased and directed to programs that follow best
practices and reach all women, including the marginalized or disadvantaged. Seven
key actions are recommended. Now is the time for action at national, regional,
and global levels.
PMID- 28691328
TI - The investment case for cervical cancer elimination.
AB - We already know what causes cervical cancer, how to prevent it, and how to treat
it, even in resource-constrained settings. Inequitable access to human
papillomavirus vaccine for girls and screening and precancer treatment for women
in low- and middle-income countries is unacceptable on ethical, social, and
financial grounds. The burden of cervical cancer falls on the poor and extends
beyond the narrow bounds of the family, affecting national economic development
and community life, as family resources are drained and poverty tightens its
grip. Proven solutions are available and the priorities for the next few years
are clear, as shown by the papers in this Supplement. Sustained political
commitment and strategic investments in cervical cancer prevention can not only
save millions of lives over the next 10 years, but can also pave the way for the
broader fight against all cancers.
PMID- 28691329
TI - Progress in HPV vaccination in low- and lower-middle-income countries.
AB - The past 10 years have seen remarkable progress in the global scale-up of human
papillomavirus (HPV) vaccinations. Forty-three low- and lower-middle-income
countries (LLMICs) have gained experience in delivering this vaccine to young
adolescent girls through pilot programs, demonstration programs, and national
introductions and most of these have occurred in the last 4 years. The experience
of Senegal is summarized as an illustrative country case study. Publication of
numerous delivery experiences and lessons learned has demonstrated the
acceptability and feasibility of HPV vaccinations in LLMICs. Four areas require
dedicated action to overcome remaining challenges to national scaling-up:
maintaining momentum politically, planning successfully, securing financing, and
fostering sustainability. Advances in policy, programming, and science may help
accelerate reaching 30 million girls in LLMICs with HPV vaccine by 2020.
PMID- 28691330
TI - Cervical cancer data and data systems in limited-resource settings: Challenges
and opportunities.
AB - Appropriate collection and use of health information is critical to the planning,
scaling up, and improvement of cervical cancer programs. The health information
systems implementation landscape is unique to each country; however, systems
serving cervical cancer programs in low-resource settings share characteristics
that present common challenges. In response, many programs have taken innovative
approaches to generating the quality information needed for decision making.
Recent advances in health information technology also provide feasible solutions
to challenges. This article draws from the experiences of the authors and from
current literature to describe outstanding challenges and promising practices in
the implementation of cervical cancer data systems, and to make recommendations
for next steps. Recommendations include engaging all stakeholders-including
providers, program managers, implementing partners, and donors-in promoting
national, district, and community information systems; building on existing
systems and processes, as well as introducing new technologies; and evolving data
collection and data systems as programs advance.
PMID- 28691331
TI - Scaling up proven innovative cervical cancer screening strategies: Challenges and
opportunities in implementation at the population level in low- and lower-middle
income countries.
AB - The problem of cervical cancer in low- and lower-middle-income countries (LLMICs)
is both urgent and important, and calls for governments to move beyond pilot
testing to population-based screening approaches as quickly as possible.
Experiences from Zambia, Bangladesh, Guatemala, Honduras, and Nicaragua, where
scale-up of evidence-based screening strategies is taking place, may help other
countries plan for large-scale implementation. These countries selected screening
modalities recommended by the WHO that are within budgetary constraints, improve
access for women, and reduce health system bottlenecks. In addition, some common
elements such as political will and government investment have facilitated action
in these diverse settings. There are several challenges for continued scale-up in
these countries, including maintaining trained personnel, overcoming limited
follow-up and treatment capacity, and implementing quality assurance measures.
Countries considering scale-up should assess their readiness and conduct careful
planning, taking into consideration potential obstacles. International
organizations can catalyze action by helping governments overcome initial
barriers to scale-up.
PMID- 28691332
TI - Advocacy, communication, and partnerships: Mobilizing for effective, widespread
cervical cancer prevention.
AB - Both human papillomavirus (HPV) vaccination and screening/treatment are
relatively simple and inexpensive to implement at all resource levels, and
cervical cancer screening has been acknowledged as a "best buy" by the WHO.
However, coverage with these interventions is low where they are needed most.
Failure to launch or expand cervical cancer prevention programs is by and large
due to the absence of dedicated funding, along with a lack of recognition of the
urgent need to update policies that can hinder access to services. Clear and
sustained communication, robust advocacy, and strategic partnerships are needed
to inspire national governments and international bodies to action, including
identifying and allocating sustainable program resources. There is significant
momentum for expanding coverage of HPV vaccination and screening/preventive
treatment in low-resource settings as evidenced by new global partnerships
espousing this goal, and the participation of groups that previously had not
focused on this critical health issue.
PMID- 28691333
TI - Treatment of cervical intraepithelial lesions.
AB - Precancerous cervical lesions precede the development of invasive cervical cancer
by 10-20 years, making cervical cancer preventable if these lesions are detected
and effectively treated. Treatment has evolved in the last few decades and now
includes ablative options that can be performed in lower-resource settings where
surgical excision is not feasible or routinely available. Gas-based cryotherapy,
which freezes cervical tissue to induce localized necrosis, is the most commonly
used ablative treatment. However, its implementation in low-resource settings is
difficult because the refrigerant gas can be difficult to procure and transport,
and is expensive. New cryotherapy devices that do not require an external supply
of gas appear promising. Thermal coagulation, which burns cervical tissue to
induce necrosis, has become more widely available in the last few years owing to
its portability and the feasibility of using battery-powered devices. These two
ablative treatments successfully eradicate 75%-85% of high-grade cervical lesions
and have minor adverse effects.
PMID- 28691334
TI - The health and economic impact of scaling cervical cancer prevention in 50 low-
and lower-middle-income countries.
AB - OBJECTIVE: To estimate the health impact, financial costs, and cost-effectiveness
of scaling-up coverage of human papillomavirus (HPV) vaccination (young girls)
and cervical cancer screening (women of screening age) for women in countries
that will likely need donor assistance. METHODS: We used a model-based approach
to synthesize population, demographic, and epidemiological data from 50 low- and
lower-middle-income countries. Models were used to project the costs (US $),
lifetime health impact (cervical cancer cases, deaths averted), and cost
effectiveness (US $ per disability adjusted life year [DALY] averted) of: (1) two
dose HPV-16/18 vaccination of girls aged 10 years; (2) once-in-a-lifetime
screening, with treatment when needed, of women aged 35 years with either HPV DNA
testing or visual inspection with acetic acid (VIA); and (3) cervical cancer
treatment over a 10-year roll-out. RESULTS: We estimated that both HPV
vaccination and screening would be very cost-effective, and a comprehensive
program could avert 5.2 million cases, 3.7 million deaths, and 22.0 million DALYs
over the lifetimes of the intervention cohorts for a total 10-year program cost
of US $3.2 billion. CONCLUSION: Investment in HPV vaccination of young girls and
cervical cancer screen-and-treat programs in low- and lower-middle-income
countries could avert a substantial burden of disease while providing good value
for public health dollars.
PMID- 28691335
TI - Cervical cancer prevention for all women: Why now?
PMID- 28691336
TI - Management algorithms for cervical cancer screening and precancer treatment for
resource-limited settings.
AB - Management algorithms for screen-positive women in cervical cancer prevention
programs have undergone substantial changes in recent years. The WHO strongly
recommends human papillomavirus (HPV) testing for primary screening, if
affordable, or if not, then visual inspection with acetic acid (VIA), and
promotes treatment directly following screening through the screen-and-treat
approach (one or two clinic visits). While VIA-positive women can be offered
immediate ablative treatment based on certain eligibility criteria, HPV-positive
women need to undergo subsequent VIA to determine their eligibility. Simpler
ablative methods of treatment such as cryotherapy and thermal coagulation have
been demonstrated to be effective and to have excellent safety profiles, and
these have become integral parts of new management algorithms. The challenges
faced by low-resource countries are many and include, from the management
perspective, identifying an affordable point-of-care HPV detection test,
minimizing over-treatment, and installing an effective information system to
ensure high compliance to treatment and follow-up.
PMID- 28691337
TI - Integrating cervical cancer screening and preventive treatment with family
planning and HIV-related services.
AB - Cervical cancer is a leading cause of mortality in Sub-Saharan Africa-in large
part because of inadequate coverage of screening and preventive treatment
services. A number of programs have begun integrating cervical cancer prevention
services into existing family planning or HIV/AIDS service delivery platforms, to
rapidly expand "screen and treat" programs and mitigate cervical cancer burden.
Drawing upon a review of literature and our experiences, we consider benefits and
challenges associated with such programs in Sub-Saharan Africa. We then outline
steps that can optimize uptake and sustainability of integrated sexual and
reproductive health services. These include increasing coordination among
implementing organizations for efficient use of resources; task shifting for
services that can be provided by nonphysicians; mobilizing communities via
trusted frontline health workers; strengthening management information systems to
allow for monitoring of multiple services; and prioritizing an operational
research agenda to provide further evidence on the cost-effectiveness and
benefits of integrated service delivery.
PMID- 28691338
TI - Optimizing secondary prevention of cervical cancer: Recent advances and future
challenges.
AB - Although human papillomavirus (HPV) vaccines offer enormous promise for the
ultimate control and possible elimination of cervical cancer, barriers to uptake
and coverage of the vaccine both in high- and low/middle-income settings mean
that advances in secondary prevention continue to be essential to prevent
unnecessary deaths and suffering from cervical cancer for decades to come. While
cytology (the Pap smear) has reduced cervical cancer incidence and prevalence in
jurisdictions where it has been systematically implemented in population-based
programs-mainly in high-income settings-limitations inherent to this method, and
to program delivery, leave many women still vulnerable to cervical cancer. Recent
evidence has confirmed that screening based on HPV testing prevents more invasive
cervical cancer and precancerous lesions, and offers innovative options such as
self-collection of specimens to improve screening uptake broadly. In this paper,
we review key advances, future opportunities, and ongoing challenges for
secondary prevention of cervical cancer using HPV-based testing.
PMID- 28691339
TI - Cancer adaptations: Atavism, de novo selection, or something in between?
AB - From an evolutionary perspective, both atavism and somatic evolution/convergent
evolution theories can account for the consistent occurrence, and astounding
attributes of cancers: being able to evolve from a single cell to a complex
organized system, and malignant transformations showing significant similarities
across organs, individuals, and species. Here, we first provide an overview of
these two hypotheses, including the possibility of them not being mutually
exclusive, but rather potentially representing the two extremes of a continuum in
which the diversity of cancers can emerge. In reviewing the current literature,
we also discuss the criteria that should be applied to discriminate between the
two competing theories and to determine their relevant contributions to
oncogenesis and cancer progression. Finally, we deliberate on the potential
applications of this conceptual framework in developing novel treatment
strategies.
PMID- 28691340
TI - Intra- and Intersexual swim bladder dimorphisms in the plainfin midshipman fish
(Porichthys notatus): Implications of swim bladder proximity to the inner ear for
sound pressure detection.
AB - The plainfin midshipman fish, Porichthys notatus, is a nocturnal marine teleost
that uses social acoustic signals for communication during the breeding season.
Nesting type I males produce multiharmonic advertisement calls by contracting
their swim bladder sonic muscles to attract females for courtship and spawning
while subsequently attracting cuckholding type II males. Here, we report intra-
and intersexual dimorphisms of the swim bladder in a vocal teleost fish and
detail the swim bladder dimorphisms in the three sexual phenotypes (females, type
I and II males) of plainfin midshipman fish. Micro-computerized tomography
revealed that females and type II males have prominent, horn-like rostral swim
bladder extensions that project toward the inner ear end organs (saccule, lagena,
and utricle). The rostral swim bladder extensions were longer, and the distance
between these swim bladder extensions and each inner-ear end organ type was
significantly shorter in both females and type II males compared to that in type
I males. Our results revealed that the normalized swim bladder length of females
and type II males was longer than that in type I males while there was no
difference in normalized swim bladder width among the three sexual phenotypes. We
predict that these intrasexual and intersexual differences in swim bladder
morphology among midshipman sexual phenotypes will afford greater sound pressure
sensitivity and higher frequency detection in females and type II males and
facilitate the detection and localization of conspecifics in shallow water
environments, like those in which midshipman breed and nest.
PMID- 28691341
TI - Divergence is not enough: the use of ecological niche models for the validation
of taxon boundaries.
AB - Delimiting taxon boundaries is crucial for any evolutionary research and
conservation regulation. In order to avoid mistaken description of species, the
approach of integrative taxonomy recommends considering multidisciplinary lines
of evidence, including ecology. Unfortunately, ecological data are often
difficult to quantify objectively. Here we test and discuss the potential use of
ecological niche models for validating taxon boundaries, using three pairs of
closely related plant taxa endemic to the south-western Alps as a case study. We
also discuss the application of ecological niche models for species delimitation
and the implementation of different approaches. Niche overlap, niche equivalency
and niche similarity were assessed both in multidimensional environmental space
and in geographic space to look for differences in the niche of three pairs of
closely related plant taxa. We detected a high degree of niche differentiation
between taxa although this result seems not due to differences in habitat
selection. The different statistical tests gave contrasting outcomes between
environmental and geographic spaces. According to our results, niche divergence
does not seem to support taxon boundaries at species level, but may have had
important consequences for local adaptation and in generating phenotypic
diversity at intraspecific level. Environmental space analysis should be
preferred to geographic space as it provides more clear results. Even if the
different analyses widely disagree in their conclusions about taxon boundaries,
our study suggests that ecological niche models may help taxonomists to reach a
decision.
PMID- 28691342
TI - Dual function of Lactobacillus kefiri DH5 in preventing high-fat-diet-induced
obesity: direct reduction of cholesterol and upregulation of PPAR-alpha in
adipose tissue.
AB - SCOPE: Kefir consumption inhibits the development of obesity and non-alcoholic
fatty liver disease (NALFD) in mice fed 60% high-fat diet (HFD). To identify the
key contributor of this effect, we isolated lactic acid bacteria (LAB) from kefir
and examined their anti-obesity properties from in vitro screening and in vivo
validation. METHODS AND RESULTS: Thirteen kefir LAB isolates were subjected to
survivability test using artificial gastrointestinal environment and cholesterol
reducing assay. Lactobacillus kefiri DH5 showed 100% survivability in
gastrointestinal environments and reduced 51.6% of cholesterol; thus, this strain
was selected for in vivo experiment. Compared to the HFD-saline group, the HFD
DH5 group showed significantly lower body weight (34.68 versus 31.10 g; p <
0.001), epididymal adipose tissue weight (1.39 versus 1.05 g; p < 0.001), blood
triglyceride (38.2 versus 31.0 mg/dL; p < 0.01) and LDL-cholesterol levels (19.4
versus 15.7 mg/dL; p < 0.01). In addition, L. kefiri DH5 administration
significantly modulated gut microbiota of HFD-fed mice. The hepatic steatosis was
significantly milder (Lesion score, 2.1 versus 1.2; p < 0.001) and adipocyte
diameter was significantly smaller (65.1 versus 42.2 MUm; p < 0.001) in the HFD
DH5 group. L. kefiri DH5 upregulated PPAR-alpha, FABP4, and CPT1 expression in
the epididymal adipose tissues (2.29-, 1.77-, and 2.05-fold change,
respectively), suggesting a reduction in adiposity by stimulating fatty acid
oxidation. CONCLUSION: L. kefiri DH5 exerts anti-obesity effects by direct
reduction of cholesterol in the lumen and upregulation of PPAR-alpha gene in
adipose tissues.
PMID- 28691343
TI - Efficacy of robust optimization plan with partial-arc VMAT for photon volumetric
modulated arc therapy: A phantom study.
AB - This study investigated position dependence in planning target volume (PTV)-based
and robust optimization plans using full-arc and partial-arc volumetric modulated
arc therapy (VMAT). The gantry angles at the periphery, intermediate, and center
CTV positions were 181 degrees -180 degrees (full-arc VMAT) and 181 degrees -360
degrees (partial-arc VMAT). A PTV-based optimization plan was defined by 5 mm
margin expansion of the CTV to a PTV volume, on which the dose constraints were
applied. The robust optimization plan consisted of a directly optimized dose to
the CTV under a maximum-uncertainties setup of 5 mm. The prescription dose was
normalized to the CTV D99% (the minimum relative dose that covers 99% of the
volume of the CTV) as an original plan. The isocenter was rigidly shifted at 1 mm
intervals in the anterior-posterior (A-P), superior-inferior (S-I), and right
left (R-L) directions from the original position to the maximum-uncertainties
setup of 5 mm in the original plan, yielding recalculated dose distributions. It
was found that for the intermediate and center positions, the uncertainties in
the D99% doses to the CTV for all directions did not significantly differ when
comparing the PTV-based and robust optimization plans (P > 0.05). For the
periphery position, uncertainties in the D99% doses to the CTV in the R-L
direction for the robust optimization plan were found to be lower than those in
the PTV-based optimization plan (P < 0.05). Our study demonstrated that a robust
optimization plan's efficacy using partial-arc VMAT depends on the periphery CTV
position.
PMID- 28691344
TI - Combined tumor genomic profiling and exome sequencing in a breast cancer family
implicates ATM in tumorigenesis: A proof of principle study.
AB - Familial breast cancers (BCs) account for 10%-20% of all diagnosed BCs, yet only
20% of such tumors arise in the context of a germline mutation in known tumor
suppressor genes such as BRCA1 or BRCA2. The vast genetic heterogeneity which
characterizes non BRCA1 and non BRCA2 (or BRCAx) families makes grouped studies
impossible to perform. Next generation sequencing techniques, however, allow
individual families to be studied to identify rare and or private mutations but
the high number of genetic variants identified need to be sorted using
pathogenicity or recurrence criteria. An additional sorting criterion may be
represented by the identification of candidate regions defined by tumor genomic
rearrangements. Indeed, comparative genomic hybridization (CGH) using single
nucleotide polymorphism (SNP) arrays allows the detection of conserved ancestral
haplotypes within recurrent regions of loss of heterozygosity, common to several
familial tumors, which can highlight genomic loci harboring a germline mutation
in cancer predisposition genes. The combination of both exome sequencing and SNP
array-CGH for a series of familial BC revealed a germline ATM mutation associated
with a loss of the wild-type allele in two BC from a BRCAx family. The analysis
of additional breast tumors from ten BC families in which a germline ATM mutation
had been identified revealed a high frequency of wild-type allele loss. This
result argues strongly in favor of the involvement of ATM in these tumors as a
tumor suppressor gene and confirms that germline ATM mutations are involved in a
subset of familial BC.
PMID- 28691345
TI - The Skyline ecosystem: Informatics for quantitative mass spectrometry proteomics.
AB - Skyline is a freely available, open-source Windows client application for
accelerating targeted proteomics experimentation, with an emphasis on the
proteomics and mass spectrometry community as users and as contributors. This
review covers the informatics encompassed by the Skyline ecosystem, from
computationally assisted targeted mass spectrometry method development, to raw
acquisition file data processing, and quantitative analysis and results sharing.
PMID- 28691346
TI - Effect of steam explosion on solid-state fermentation of maize stalk by
Penicillium decumbens and Phanerochaete chrysosporium for animal feed production.
AB - Pre-treated maize stalk could be used for animal feed due to the improved
digestibility. Steam explosion (SE) and solid-state fermentation (SSF) are two
methods in maize stalk pre-treatment. To evaluate the effect of combination of SE
and SSF on the maize stalk pre-treatment, the maize stalk was treated with steam
explosion and microbial fermentation with Penicillium decumbens and Phanerochate
chrysporium in this study. The steam explosion severity (logR0 ) affected
component of the corn stover and then affected the SSF. The highest weight loss
of substrate (23.20%), protein (12.71%) and cellulase filter paper activity (FPA)
(7.42IU/g) could be obtained at logR0 = 3.64 and the IVDMD of SE-SSF-treated
straw could reach 75.8%. The SE-SSF pre-treatment method could improve the
utilization of straw as animal feed and overcome the shortage of feed source in
animal husbandry.
PMID- 28691347
TI - Design and operation of a continuous integrated monoclonal antibody production
process.
AB - The realization of an end-to-end integrated continuous lab-scale process for
monoclonal antibody manufacturing is described. For this, a continuous
cultivation with filter-based cell-retention, a continuous two column capture
process, a virus inactivation step, a semi-continuous polishing step (twin-column
MCSGP), and a batch-wise flow-through polishing step were integrated and operated
together. In each unit, the implementation of internal recycle loops allows to
improve the performance: (a) in the bioreactor, to simultaneously increase the
cell density and volumetric productivity, (b) in the capture process, to achieve
improved capacity utilization at high productivity and yield, and (c) in the
MCSGP process, to overcome the purity-yield trade-off of classical batch-wise
bind-elute polishing steps. Furthermore, the design principles, which allow the
direct connection of these steps, some at steady state and some at cyclic steady
state, as well as straight-through processing, are discussed. The setup was
operated for the continuous production of a commercial monoclonal antibody,
resulting in stable operation and uniform product quality over the 17 cycles of
the end-to-end integration. The steady-state operation was fully characterized by
analyzing at the outlet of each unit at steady state the product titer as well as
the process (HCP, DNA, leached Protein A) and product (aggregates, fragments)
related impurities. (c) 2017 American Institute of Chemical Engineers Biotechnol.
Prog., 33:1303-1313, 2017.
PMID- 28691348
TI - Rare complication of fibroids in pregnancy: Spontaneous fibroid rupture.
AB - Uterine fibroids in pregnancy present with numerous complications. However,
spontaneous rupture is a rare and potentially life-threatening event. We report a
case of a 43-year-old multiparous woman who presented with hypovolemic shock
secondary to a ruptured uterine fibroid 2 days after a spontaneous vaginal
delivery. Emergency laparotomy confirmed massive intra-abdominal hemorrhage from
the ruptured capsule of a 10-cm subserosal fibroid. A myomectomy was performed.
Her postoperative recovery period was uneventful. This case is very rare, with
fewer than 30 cases of hemoperitoneum secondary to rupture of fibroids having
been reported in published works. It demonstrates how a benign and common
condition, such as fibroids, can lead to an obstetric emergency that mimics a
surgical abdomen requiring swift diagnosis and surgical intervention.
PMID- 28691349
TI - Ovsynch Plus protocol improves ovarian response in anovular Murrah buffaloes in
low-breeding season.
AB - The objective of the study was to evaluate the efficacy of ovarian response and
pregnancy rate in anovular buffaloes following Ovsynch and Ovsynch Plus
protocols. Buffaloes (n = 55) were divided into two groups: Ovsynch group (n =
26): GnRH (10 MUg, GnRH1) on Day 0, PGF2 alpha (25 mg) on Day 7, GnRH (10 MUg,
GnRH2) on Day 9; Ovsynch Plus group (n = 29): 500 IU equine chorionic
gonadotropin (eCG) 72 hr (day -3) prior to Ovsynch protocol, followed by fixed
timed artificial insemination (FTAI) 6 and 24 hr after GnRH2 injection in bot
groups. Transrectal ultrasonography was performed daily, that is, from day 0 and
3 in Ovsynch and Ovsynch Plus group, respectively for ovarian response and
pregnancy diagnosis at day 30 post-insemination. In Ovsynch Plus group,
administration of eCG prior to GnRH1 increased (p < .001) the diameter (mm) of
dominant follicle (DF) from 10.15 +/- 0.26 to 12.23 +/- 0.34 within 72 hr of
treatment resulting higher ovulatory response to GnRH1. Ovulation after GnRH1 was
higher (p < .01) in Ovsynch Plus group (96.6%) than Ovsynch group (61.5%).
However, ovulation rate to GnRH2 was similar (p > .05) between groups (Ovsynch
group: 76.9% vs. Ovsynch Plus group: 70.0%). Mean DF diameter (mm) that ovulated
to both GnRHs was higher (p < .01) than non-ovulated counterparts in both groups
(Ovsynch group: 10.80 +/- 0.27 vs. 8.47 +/- 0.53; Ovsynch Plus group: 11.99 +/-
0.24 vs. 9.5 +/- 0.63). Pregnancy was established in buffaloes which responded to
both GnRHs, irrespective of groups, being higher (p = .52) in Ovsynch Plus group
(34.5%) than Ovsynch group (23.1%), though non-significant. In summary, this
study showed that eCG inclusion prior to Ovsynch regimen improves ovulatory
response in anovular buffaloes during low-breeding season.
PMID- 28691350
TI - Serum testosterone, sperm quality, cytological, physicochemical and biochemical
characteristics of the prostatic fraction of dogs with prostatomegaly.
AB - Prostatomegaly is a common finding in older non-neutered dogs. This study
compared the serum testosterone, sperm quality and characteristics of the
prostatic fraction between healthy dogs and dogs with prostatomegaly. Blood
samples of ten dogs (five dogs from each group) were taken for serum testosterone
measurement. Sperm motility, vigour, concentration, viability, membrane
functionality and morphology were analysed in sperm-rich fraction. Osmolality,
pH, cell types, and albumin, haemoglobin, acid phosphatase, alkaline phosphatase,
glucose, triglycerides, cholesterol, calcium, phosphorus, magnesium and chloride
were analysed in prostatic fraction. Dogs with prostatomegaly have the lowest
sperm motility, vigour, concentration and functional membrane. Dogs with
prostatomegaly have the highest glucose, triglycerides and cholesterol. Glucose
was the only constituent positively correlated with serum testosterone and
prostate volume. It can be concluded that dogs with prostatomegaly have poorer
sperm quality, and glucose, triglycerides and cholesterol in prostatic fraction
can be used as prostatomegaly biomarkers.
PMID- 28691351
TI - Structures of designed armadillo repeat proteins binding to peptides fused to
globular domains.
AB - Designed armadillo repeat proteins (dArmRP) are alpha-helical solenoid repeat
proteins with an extended peptide binding groove that were engineered to develop
a generic modular technology for peptide recognition. In this context, the term
"peptide" not only denotes a short unstructured chain of amino acids, but also an
unstructured region of a protein, as they occur in termini, loops, or linkers
between folded domains. Here we report two crystal structures of dArmRPs, in
complex with peptides fused either to the N-terminus of Green Fluorescent Protein
or to the C-terminus of a phage lambda protein D. These structures demonstrate
that dArmRPs bind unfolded peptides in the intended conformation also when they
constitute unstructured parts of folded proteins, which greatly expands possible
applications of the dArmRP technology. Nonetheless, the structures do not fully
reflect the binding behavior in solution, that is, some binding sites remain
unoccupied in the crystal and even unexpected peptide residues appear to be
bound. We show how these differences can be explained by restrictions of the
crystal lattice or the composition of the crystallization solution. This
illustrates that crystal structures have to be interpreted with caution when
protein-peptide interactions are characterized, and should always be correlated
with measurements in solution.
PMID- 28691352
TI - Low cost-effectiveness of routine use of optical coherence tomography in pre
cataract surgery.
PMID- 28691353
TI - Reproductive performance of immobilized cryopreserved bovine semen used for timed
artificial insemination.
AB - The SpermVital(r) technology comprises embedding of spermatozoa within an
alginate gel to facilitate release of sperm cells over a prolonged period in
utero after AI. The aim of this study was to examine whether the survival time of
spermatozoa is extended when applying this immobilization technology in
combination with cryopreservation. Sperm cell survival (acrosome and plasma
membrane integrity) was studied in vitro for 48 hr at physiological temperature.
One dose of SpermVital(r) (SV) semen was compared with single doses of Biladyl(r)
(B) processed semen as well as double doses of B (B double). B double was
obtained by adding a second B dose the following day, thereby mimicking double
AI. Furthermore, reproductive performance applying single early timed AI (TAI)
with SV following oestrus synchronization was studied in a field trial. Double
insemination (TAI on two consecutive days) with B semen served as control. Number
of acrosome-intact live sperm cells decreased over time in vitro for all
treatments (p < .05). There was no difference between SV sperm cell survival and
B double after 24 hr (p > .05). However, after 48 hr, SV sperm cell survival was
higher than B double (p < .05). Moreover, multivariate analysis showed that the
outcome of single early TAI with SV was not significantly different from B double
(p > .05). Likelihood of pregnancy and calving in the heifer group was higher
than in the cow group (p < .05). These results imply that spermatozoa immobilized
in alginate gel have prolonged survival.
PMID- 28691354
TI - Feasibility of a wait-and-scan period as initial management strategy for head and
neck paraganglioma.
AB - BACKGROUND: The main goal of head and neck paraganglioma (PGL) management is
reduction of treatment-induced and tumor-induced complications. In the current
study, tumor growth rates and tumor-induced complications during a wait-and-scan
period are evaluated. METHODS: This was a retrospective cohort study. Tumor
growth was measured in axial plane diameter and tumor volume. RESULTS: Of 59
jugulotympanic tumors, 71 carotid body tumors, and 29 vagal body tumors, 44% were
growing (median follow-up of 63.6 months). Median growth rates were 0.41 mm/year
(range 0-439 mm), 1.6 mm/year (range 0-23.68 mm), and 1.6 mm/year (range 0-23.68
mm) respectively. Growth was significantly correlated to age at presentation
(odds ratio [OR] = 0.974; P < .05). Seventeen tumors induced 20 complications.
Six of these tumors were growing, and growth rates were higher than in tumors not
inducing complications (P = .016; F = 6.496). CONCLUSION: These results
illustrate the feasibility of a wait-and-scan strategy for head and neck PGL. The
management strategy could not prevent tumor-induced complications in 16% of
nongrowing tumors.
PMID- 28691355
TI - Ultrastrong and Tough Supramolecular Hydrogels from Multiurea Linkage Segmented
Copolymers with Tractable Processablity and Recyclability.
AB - Strong and tough synthetic hydrogels have received ever-increasing interests due
to their potential applications as load-bearing structural materials. However,
strong, tough, and recyclable hydrogels in different forms that can be generated
by different methods according to various practical applications still remain an
intrinsic bottleneck. A simple one-pot synthesis of multiurea linkage segmented
linear copolymers with easy recyclability, hybridization, and processability,
including compression molding, solution casting, and spinning methods, to yield
ultrastrong and tough hydrogel films or stretchable hydrogel fibers with
diameters ranged from macro-, micro-, to nanoscale, is reported here.
PMID- 28691356
TI - Tumor microenvironment and noncoding RNAs as co-drivers of epithelial-mesenchymal
transition and cancer metastasis.
AB - Reciprocal interactions between cancer cells and tumor microenvironment (TME) are
crucial events in tumor progression and metastasis. Pervasive stromal
reprogramming of TME modifies numerous cellular functions, including
extracellular matrix (ECM) stiffness, inflammation, and immunity. These
environmental factors allow selection of more aggressive cells that develop
adaptive strategies associating plasticity and epithelial-mesenchymal transition
(EMT), stem-like phenotype, invasion, immunosuppression, and resistance to
therapies. EMT is a morphomolecular process that endows epithelial tumor cells
with mesenchymal properties, including reduced adhesion and increased motility.
Numerous studies have demonstrated involvement of noncoding RNAs (ncRNAs), such
as miRNAs and lncRNAs, in tumor initiation, progression, and metastasis. NcRNAs
regulate every hallmark of cancer and have now emerged as new players in
induction and regulation of EMT. The reciprocal regulatory interactions between
ncRNAs, TME components, and cancer cells increase the complexity of gene
expression and protein translation in cancer. Thus, deeper understanding of
molecular mechanisms controlling EMT will not only shed light on metastatic
processes of cancer cells, but enhance development of new therapies targeting
metastasis. In this review, we will provide recent findings on the role of known
ncRNAs relevant to EMT and cancer metastasis and discuss the role of the
interaction between ncRNAs and TME as co-drivers of EMT. Developmental Dynamics
247:405-431, 2018. (c) 2017 Wiley Periodicals, Inc.
PMID- 28691357
TI - Seniors centre-based health intervention programmes in the United States and
South Korea: A systematic review.
AB - BACKGROUND: Despite the great need for health interventions among seniors centre
participants, this matter has received little attention. AIM AND DESIGN: This
systematic review aimed to identify what types of health interventions are
effective and feasible for seniors centre participants. DATA SOURCES: MEDLINE,
Ovid, CINAHL, Google Scholar, EMBASE, and RISS were searched. REVIEW METHODS: We
searched for health intervention studies conducted in seniors centres published
in English and Korean between 1990 and 2014. Of 907 screened articles, 22 studies
of all types of experimental designs were selected. RESULTS: Selected studies
were grouped by intervention domain: health promotion (n = 8), safety (n = 5),
chronic disease management (n = 6), and comprehensive wellness (n = 3). Overall,
59.1% of the interventions were provided by nurses. The health interventions
resulted in positive effects on seniors centre participants' knowledge, health
behaviours, clinical indices, and hospitalization rates. Few studies reported on
feasibility outcomes such as satisfaction and cost-effectiveness. CONCLUSIONS:
Considering the impact and ease of access to older people at seniors centres,
health interventions and services within seniors centres should be strengthened.
There is potential for nursing to spearhead seniors centre health intervention
programmes to enhance active ageing for participants.
PMID- 28691358
TI - Survival benefit of surgical approach for advanced oropharyngeal and
hypopharyngeal cancer: A retrospective analysis.
AB - BACKGROUND: Head and neck cancer is increasingly being managed through
nonsurgical approaches. Evidence comes from studies that have mainly examined
patients with laryngeal cancer. Few studies, with limited sample size, have
focused on the comparative outcomes of surgical and nonsurgical approaches in
patients with advanced oropharyngeal or hypopharyngeal cancer. METHODS: Using a
national cancer database, we identified 1603 and 1512 patients with clinical
stage III/IVA oropharyngeal and hypopharyngeal cancer, respectively, treated
between 2004 and 2009. The study cohort was followed until 2012, and analyzed
through Kaplan-Meier survival analysis and Cox regression. RESULTS: Overall,
31.4% of patients with advanced oropharyngeal cancer and 42.2% of patients with
hypopharyngeal cancer received surgery as their primary treatment. Receiving
primary surgery for advanced oropharyngeal and hypopharyngeal cancer was
associated with higher survival rates after controlling for potential
confounders. CONCLUSION: We recommend that surgery be considered a first-line
treatment for advanced oropharyngeal and hypopharyngeal cancers.
PMID- 28691359
TI - Chronic histiocytic intervillositis in three consecutive pregnancies in a single
patient: Differing clinical results and pathology according to treatment used.
AB - Chronic histiocytic intervillositis (CHI) is an extremely rare pathological
condition but is strongly associated with severe obstetric complications and has
a high recurrence rate. The management of this condition has not yet been
established. We describe herein the occurrence of CHI in the late second-third
trimester in each of three consecutive pregnancies in a single patient with four
previous consecutive early miscarriages. In this patient, each of the three
complicated pregnancies was managed with one of the following, respectively: low
dose aspirin; heparin plus low-dose aspirin; and prednisolone plus low-dose
aspirin. CHI was histologically confirmed in all three pregnancies, but the
clinical results and pathology (e.g. extent of histiocytic infiltration) in each
pregnancy clearly differed with treatment. Both combination treatments eventuated
in a live birth. Immunosuppressive therapy seemed to produce better clinical
results by restricting the extent of the affected areas. The elevated alkaline
phosphatase associated with the CHI was assumed to have no clinical prognostic
value.
PMID- 28691360
TI - Effect of lidocaine spray during colposcopy-directed cervical biopsy: A
randomized controlled trial.
AB - AIM: We aimed to examine the effect of lidocaine spray in reducing pain during
colposcopy-directed cervical biopsy (CDB). METHODS: Two hundred women with
abnormal cervical screening test results and abnormal colposcopic findings that
required a CDB during April to December 2015 were enrolled. The participants were
randomly assigned into one of two groups. For group 1 (lidocaine group), 10%
lidocaine spray was applied thoroughly to the ectocervix. For group 2, no
anesthesia was given. The primary outcome of this study was the biopsy pain
score. RESULTS: Of the 200 women enrolled, 100 were randomly assigned to group 1
and 100 were in group 2. The baseline, biopsy, and postprocedure pain scores were
comparable between the study groups. The mean difference between the biopsy and
the baseline pain scores and the mean difference of the postprocedure pain scores
from baseline were statistically significantly higher in the no-anesthesia group
(group 2), P = 0.01 and P = 0.02, respectively. However, the degree of pain was
minimal in both groups. There were no complications observed in any participants.
CONCLUSION: Lidocaine spray reduces pain during colposcopy-directed cervical
biopsy; however, the clinically meaningful effect of such a procedure cannot be
demonstrated in this study.
PMID- 28691361
TI - Impact of childhood trauma on cognitive profile in bipolar disorder.
AB - OBJECTIVES: Bipolar Disorder (BD) is associated with cognitive impairment even
during remission periods. Nonetheless, this impairment seems to adjust to
different profiles of severity. Our aim was to examine the potential impact of
childhood trauma (CT) on cognitive performance and, more specifically, on
neurocognitive profile membership. METHODS: Using a data-driven strategy, 113
euthymic bipolar patients were grouped according to their cognitive performance
using a hierarchical clustering technique. Patients from the three resulting
clusters, the so-called "low", "average", and "high performance" groups, were
then compared in terms of main sociodemographic, clinical and functioning
variables, including CT measures. One-way ANOVA, a chi-square test and partial
correlations were used for this purpose, as appropriate. A multinomial logistic
regression model was used to determine which variables contributed to
neurocognitive clustering membership. RESULTS: Patients from the three
neurocognitive clusters differed in terms of sociodemographic, clinical,
functioning and CT variables. Scores on the Childhood Trauma Questionnaire (CTQ),
especially on the physical negligence subscale, were also associated with a poor
cognitive performance. The multinomial regression model indicated that CTQ total
scores and the estimated intelligence quotient (IQ) significantly contributed to
differentiation among the three neurocognitive groups. CONCLUSIONS: Our results
confirmed that CT significantly impacts on cognitive performance during adulthood
in BD. The data obtained suggest that a history of CT could act as a liability
marker for cognitive impairment. A higher estimated IQ may act as a protective
factor against cognitive decline in this group of patients.
PMID- 28691362
TI - Basal-bolus insulin therapy reduces maternal triglycerides in gestational
diabetes without modifying cholesteryl ester transfer protein activity.
AB - AIM: Macrosomia in the offspring of overweight/obese mothers with glucose
controlled gestational diabetes mellitus (GDM) is due to excessive rise of
maternal triglycerides (TG). We aimed to ascertain whether basal-bolus insulin
therapy (BBIT), or other components of the treatment, could reduce TG in GDM.
METHODS: We studied the records of 131 singleton pregnancies with GDM, using
stepwise multiple linear regression, Mann-Whitney, chi2 , and Jonckheere-Terpstra
tests. As maternal TG increased steadily during normal pregnancy, these were
transformed as z-scores. The atherogenic index of plasma (AIP) was calculated as
a measure of cholesteryl ester transfer protein activity. RESULTS: Multiple
regression showed that only BBIT (but neither limitation of weight gain nor
metformin) reduced maternal TG z-scores (P = 0.011). When the 131 pregnancies
were split into two groups - without BBIT (n = 58; HbA1c = 5.3 +/- 0.3%) and with
BBIT (n = 73; HbA1c = 5.4 +/- 0.6; P = 0.2005) - we observed that BBIT (n = 73)
reduced maternal TG z-scores in a dose-related fashion (Jonckheere-Terpstra P =
0.03817). The atherogenic index of plasma remained within normal range in both
groups. CONCLUSION: BBIT (but not weight gain control nor metformin) reduced
maternal TG in mothers with glucose-controlled GDM. This beneficial effect of
BBIT was not related to changes in the cholesteryl ester transfer protein
activity.
PMID- 28691363
TI - Glaucoma Australia educational impact study: a randomized short-term clinical
trial evaluating the association between glaucoma education and patient
knowledge, anxiety and treatment satisfaction.
AB - IMPORTANCE: Targeted education may impact glaucoma patients' clinical experience.
BACKGROUND: The aim of this study was to measure the impact of patient-centred
glaucoma-related education on knowledge, anxiety and treatment satisfaction.
DESIGN: This was a multicentre Australia-wide randomized clinical trial.
PARTICIPANTS: One hundred one newly diagnosed glaucoma patients were randomized
1:1 to intervention or control groups. METHODS: Those randomized to the Glaucoma
Australia educational intervention received telephone-based counselling about
glaucoma followed by mail-out information, in addition to usual care and
information from their treating ophthalmologist. The control group received only
usual care and information from their treating ophthalmologist. Surveys were
administered at baseline and 4 weeks following intervention. MAIN OUTCOME
MEASURES: The Auckland Glaucoma Knowledge Questionnaire measured glaucoma-related
knowledge. The Hospital Anxiety and Depression Scale and Eye-Drop Satisfaction
Questionnaire measured anxiety and patient treatment satisfaction, respectively.
RESULTS: Mean age was 64.7 +/- 11.1 years, and 52 (51.5%) were male. There was no
noticeable increase in knowledge levels in the control group (mean difference:
0.04 logits, P = 0.7), compared with a 0.49-logit (P = 0.02) increase in
knowledge levels in the intervention group. Between-group comparison showed a non
significant increase in knowledge (0.45 logits, P = 0.07) comparing intervention
participants with controls. Intervention participants experienced a statistically
significant decrease in anxiety compared to controls (-0.60 logits, P = 0.02). No
between-group difference was found in Eye-Drop Satisfaction Questionnaire scores.
CONCLUSIONS AND RELEVANCE: Patient-centred glaucoma-related education and support
services may improve knowledge and can reduce anxiety for newly diagnosed
glaucoma patients. All glaucoma patients should be adequately counselled about
the nature of the disease and its management.
PMID- 28691364
TI - Synthesis of the Epimeric Secosteroids Strophasterols A and B.
AB - Two epimeric rearranged ergostanes, strophasterols A and B, with an unprecedented
carbon skeleton were synthesized from ergosterol, both in 17 steps via a common
secosteroidal intermediate. The conversion of ergosterol into the pivotal
intermediate involved an efficient acid-catalyzed double-bond migration from ring
B to ring D, oxidative cleavage of the double bond, and a completely
diastereoselective acyl radical cyclization to form an isolated cyclopentanone
ring unique to this recently discovered family of steroidal compounds produced by
mushrooms. The intermediate was transformed stereodivergently into two epimeric
cyclopentane derivatives through hydrogenation using two types of catalysts. One
epimer was elaborated into strophasterol B by utilizing peracid oxidation of an
iodide to provide an epoxide directly, and the other epimer was elaborated into
strophasterol A, which is known to be a suppressor of endoplasmic reticulum
stress.
PMID- 28691366
TI - A case of post-partum non-sexually acquired genital ulceration.
PMID- 28691365
TI - Cooperation between p21 and Akt is required for p53-dependent cellular
senescence.
AB - Cellular senescence has been implicated in normal aging, tissue homeostasis, and
tumor suppression. Although p53 has been shown to be a central mediator of
cellular senescence, the signaling pathway by which it induces senescence remains
incompletely understood. In this study, we have shown that both Akt and p21 are
required to induce cellular senescence in response to p53 expression. In a p53
induced senescence model, we found that Akt activation was essential for inducing
a cellular senescence phenotype. Surprisingly, Akt inhibition did not abolish p53
induced cell cycle arrest, but it suppressed the increase in intracellular
reactive oxygen species (ROS) levels. The results of the cell cycle and
morphological analysis suggest that p53 induced quiescence, not senescence,
following Akt inhibition. Conversely, the inhibition of p21 induction abolished
cell cycle arrest but did not affect the p53-induced increase in ROS levels.
Additionally, p21 and Akt separately controlled cell cycle arrest and ROS levels,
respectively, during H-Ras-induced senescence in human normal fibroblasts. The
mechanistic analysis revealed that Akt increased ROS levels through NOX4
induction, and increased Akt-dependent NF-kappaB binding to the NOX4 promoter is
responsible for NOX4 induction upon p53 expression. We further showed that Akt
activation upon p53 expression is mediated by mammalian target of rapamycin
complex 2. In addition, p53-mediated IL6 and IL8 induction was abrogated by Akt
inhibition, suggesting that Akt activation is also required for the senescence
associated secretory phenotype. Collectively, these results suggest that p53
simultaneously controls multiple pathways to induce cellular senescence through
p21 and Akt.
PMID- 28691367
TI - Photoinduced Trans-to-cis Phase Transition of Polycrystalline Azobenzene at Low
Irradiance Occurs in the Solid State.
AB - The ability to produce large-scale, reversible structural changes in a variety of
materials by photoexcitation of a wide variety of azobenzene derivatives has been
recognized for almost two decades. Because photoexcitation of trans-azobenzene
produces the cis-isomer in solution, it has generally been inferred that the
macroscopic structural changes occurring in materials are also initiated by a
similar large-amplitude trans-to-cis isomerization. This work provides the first
demonstration that a trans-to-cis photoisomerization occurs in polycrystalline
azobenzene, and is consistent with the previously hypothesized nature of the
trigger in the photoactuated mechanisms of the materials in question. It is also
demonstrated that under low irradiance, trans-to-cis isomerization occurs in the
solid (not via a pre-melted phase); and the presence of the cis-isomer thus
lowers the melting point of the sample, providing a liquid phase. A variety of
experimental techniques were employed, including X-ray diffraction measurements
of polycrystalline azobenzene during exposure to laser irradiation and
fluorescence measurements of the solid sample. A practical consequence of this
work is that it establishes trans-azobenzene as an easily obtainable and well
defined control for monitoring photoinduced structural changes in X-ray
diffraction experiments, using easily accessible laser wavelengths.
PMID- 28691368
TI - Epitopes and motifs of the HLA-B*14 allele family products and related HLA-B14
cross-reactive specificities.
AB - The split specificities of HLA-B14 (B64, B65) are assigned to the B*14:01 (B64)
and B*14:02 (B65) products only. Of the further 50 B*14 expressed products, only
B*14:03 and B*14:06 are officially designated as HLA-B14. The B*14:08 product
differs from B64 by a single amino acid substitution of W97R, while the B*14:53
specificity (which is a "short" B14 and neither B64 nor B65) differs from B64 by
three residues (W97S, Y113H and F116Y). Comprehensive testing of B*14:08:01 cells
(using 49 alloantisera with B64 or B64, B65 specificities, and five monoclonal
antibodies with B65 or B64, B65 activity) showed that the B*14:08 specificity is,
like the B*14:53 product, neither B64 nor B65 and appears as a "short" B14
specificity. To help understand the serological reactivity of the B*14:08 and
B*14:53 products, and B64 and B65, we identified seven published epitopes (11AV,
97W, 61ICT, 116F, 131S+163T, 170RH and 420) and, by inspection, 29 motifs, that
encompass one or more of B64, B65 and various HLA-B14 cross-reactive group
specificities. We then considered the possession of these epitopes and motifs by
the products of B*14:01 to B*14:06, B*14:08 and B*14:53. Seventeen of the 29
motifs fully complied with the one-/two-patch functional epitope concept for
amino acid proximity, as determined by Cn3D software, the remainder partially
complied. The nature and patterns of epitopes and motifs possessed by both
B*14:08 and B*14:53 specificities supported their designation as HLA-B14 but non
B64/B65. Also that epitope 97W, with 11S or 11A, is critical for serological B64
and B65 reactivity. And conversely, that epitope 116F, and several identified
motifs, are probably unimportant for HLA-B14 antibody reactivity. The previous
submission that the B*14:03 specificity is HLA-B65 was compatible with its
epitope/motif pattern. B*14:04 cells would also be expected to react as B65,
based on its epitope/motif pattern, and not as B64 as previously implied. Also,
from their epitope/motif patterns, and external serological information, it is
probable that the B*14:05 and B*14:06 specificities will both appear as "short"
HLA-B14, non-B64/B65. Several epitopes and motifs encompassed a range of HLA-B
specificities included in the serological HLA-B14 cross-reactive group, thus
supporting these original serological findings.
PMID- 28691369
TI - Comprehensive Examination of Mechanical and Diffusional Effects on Cell Behavior
Using a Decoupled 3D Hydrogel System.
AB - Hydrogels possess several physical and chemical properties suitable for
engineering cellular environments for biomedical applications. Despite recent
advances in hydrogel systems for cell culture, it is still a significant
challenge to independently control the mechanical and diffusional properties of
hydrogels, both of which are well known to influence various cell behaviors when
using hydrogels as 3D cell culture systems. Controlling the crosslinking density
of a hydrogel system to tune the mechanical properties inevitably affects their
diffusional properties, as the crosslinking density and diffusion are often
inversely correlated. In this study, a polymeric crosslinker is demonstrated that
allows for the adjustment of the degree of substitution of reactive functional
groups. By using this polymeric crosslinker, the rigidity of the resulting
hydrogel is controlled in a wide range without changing the polymer
concentration. Furthermore, their diffusional properties, as characterized by
their swelling ratios, pore diameters, and drug release rates, are not
significantly affected by the changes in the degree of substitution. 3D cell
studies using this hydrogel system successfully demonstrate the varying effects
of mechanical properties on different cell types, whereas those in a conventional
hydrogel system are more significantly influenced by changes in diffusional
properties.
PMID- 28691370
TI - Bioaccessibility, bioavailability, and anti-inflammatory effects of anthocyanins
from purple root vegetables using mono- and co-culture cell models.
AB - SCOPE: Immune-inflammatory signaling and metabolic effects are the main pillars
for bioactivity of anthocyanins derived from highly pigmented root vegetables.
This study aims to assess the bioaccessibility and bioavailability of purple
carrot and potato derived anthocyanins and the molecular mechanisms of their
ability to ameliorate cellular inflammation in a mono- and co-culture cell
models. METHODS AND RESULTS: An in vitro gastrointestinal model was used and
demonstrated bioaccessibility of 44.62 and 71.8% for anthocyanins of purple
carrot and potato, respectively. These accessible anthocyanins significantly
inhibited cellular inflammation in Caco-2 cells. Intact cyanidinglycoside or
petunidinglycoside (respectively from carrots and potatoes) were transported
across a transmembrane cell model and detected by LC-MS/MS. Computational docking
and glucose uptake analyses suggested uptake of anthocyanins was mediated by
hexose transporters. Subsequent experiment using an inflamed Caco-2 BBe1/THP-1 co
culture cell model showed these transported anthocyanins inhibited IL-8 and TNF
alpha secretion,and expression of pro-inflammatory cytokines by blocking NF
kappaB, and MAPK mediated inflammatory cellular signaling cascades, but with
varying degrees due to structural features. CONCLUSION: Anthocyanins from purple
carrots and potatoes possess a promising anti-inflammatory effect in model gut
system. They can be absorbed and act differently but are in general beneficial
for inflammation-mediated diseases.
PMID- 28691371
TI - Approaches to identify kinase dependencies in cancer signalling networks.
AB - Cells integrate extracellular signals into appropriate responses through a
complex network of biochemical reactions driven by the activity of protein and
lipid kinases, among other proteins. In order to understand this complexity, new
approaches, both experimental and computational, have recently been developed
with the aim to identify regulatory kinases and infer their activation status in
the context of their signalling network. Here, we review such approaches with
particular focus on those based on phosphoproteomics. Integration of kinase
activity measurements inferred from phosphoproteomics data with other 'omics'
datasets is starting to be used to identify regulatory nodes in biochemical
networks. These methodologies may in the future be used to identify patient
specific targets and thus advance personalised cancer medicine.
PMID- 28691372
TI - Cutaneous infiltration of anaplastic variant of CD30-positive diffuse large B
cell lymphoma.
PMID- 28691373
TI - Stromal Vascular Fraction Loaded Silk Fibroin Mats Effectively Support the
Survival of Diabetic Mice after Pancreatic Islet Transplantation.
AB - The aim of this study is to assess whether stromal vascular fraction (SVF)-soaked
silk fibroin nonwoven mats (silk-SVF) can preserve the functionality of
encapsulated pancreatic endocrine cells (alginate-PECs) after transplantation in
the subcutaneous tissue of diabetic mice. Silk scaffolds are selected to create
an effective 3D microenvironment for SVF delivery in the subcutaneous tissue
before diabetes induction: silk-SVF is subcutaneously implanted in the dorsal
area of five healthy animals; after 15 d, mice are treated with streptozotocin to
induce diabetes and then alginate-PECs are implanted on the silk-SVF. All animals
appear in good health, increasing weight during time, and among them, one
presents euglycemia until the end of experiments. On the contrary, when PECs are
simultaneously implanted with SVF after diabetes induction, mice are euthanized
due to suffering. This work clearly demonstrates that silk-SVF creates a
functional niche in subcutaneous tissue and preserves endocrine cell survival and
engraftment.
PMID- 28691374
TI - Multi-target Fragments Display Versatile Binding Modes.
AB - Promiscuity is an interesting concept in fragment-based drug design as fragments
with low specificity can be advantageous for finding many screening hits. We
present a PDB-wide analysis of multi-target fragments and their binding mode
conservation. Focussing on multi-target fragments, we found that the majority
shows non-conserved binding modes, even if they bind in a similar conformation or
similar protein targets. Surprisingly, fragment properties alone are not able to
predict whether a fragment will exhibit a versatile or conserved binding mode,
emphasizing the interplay between protein and fragment features during a binding
event and the importance of structure-based modelling.
PMID- 28691375
TI - Gender differences in preferences for psychological treatment, coping strategies,
and triggers to help-seeking.
AB - OBJECTIVE: There is some evidence that men and women deal with stress in
different ways; for example, a meta-analysis found that women prefer to focus on
emotions as a coping strategy more than men do. However, sex differences in
preferences for therapy is a subject little explored. DESIGN: A cross-sectional
online survey. METHOD: Participants (115 men and 232 women) were recruited via
relevant websites and social media. The survey described therapies and asked
participants how much they liked each. Their coping strategies and help-seeking
behaviour were assessed too. RESULTS: Survey data were analysed using multiple
linear regression. After familywise adjustment of the alpha for multiple testing
to p < .0125, and controlling for other relevant variables, men liked support
groups more than women did (beta = -.163, p < .010), used sex or pornography to
cope with stress more than women did (Exp[B] = .280, p < .0002), and thought that
there is a lack of male-friendly options more than women did (Exp[B] = .264, p <
.002). The majority of participants expressed no preference for the sex of their
therapist, but of those who did, men were only slightly more likely to prefer a
female therapist whereas women were much more likely to prefer females (p <
.0004). Even after familywise adjustment, there were still more significant
findings than would be expected by chance (p < .001, two-tailed). CONCLUSIONS:
Although there are many similarities in the preferences of men and women
regarding therapy, our findings support the hypothesis that men and women show
statistically significant differences of relevance to clinical psychologists.
PRACTITIONER POINTS: Men are less inclined than women to seek help for
psychological issues This study demonstrates that men and women show significant
differences in some aspects of therapy, coping behaviour, and help-seeking It is
possible that men would be more inclined to seek help if therapies catered more
for men's preferences Practitioners can learn to improve the success of their
practice by taking the gender of clients into account.
PMID- 28691376
TI - Adult-onset Still's disease-like condition due to alcoholic hepatitis and vitamin
B deficiency.
PMID- 28691377
TI - Effectiveness of 8- or 12-weeks of ledipasvir and sofosbuvir in real-world
treatment-naive, genotype 1 hepatitis C infected patients.
AB - BACKGROUND: Treatment of genotype 1 hepatitis C virus (HCV) infection with
combination direct acting anti-virals is associated with very high rates of
sustained virological response (SVR). Daily combination of ledipasvir and
sofosbuvir for 12 weeks is approved for the treatment of genotype 1 HCV patients,
though noncirrhotic patients who are naive to treatment with a baseline HCV RNA
<6 million IU/mL can be treated for 8 weeks. This guidance stemmed from a post
hoc analysis of the ION 3 clinical trial, which demonstrated similar SVR for
patients treated with ledipasvir and sofosbuvir with or without ribavirin for 8
or 12 weeks. AIM: To compare the SVR for 8 weeks vs 12 weeks of ledipasvir and
sofosbuvir in HCV infected patients in a real-world setting. METHODS: We
performed an observational real-world cohort study of treatment success following
8 or 12 weeks of ledipasvir and sofosbuvir for treatment-naive genotype 1 HCV
patients. RESULTS: A total of 826 patients were treated for either 8 (n=252) or
12 weeks (n=574) with ledipasvir and sofosbuvir and achieved SVR rate of 95.3%
and there was no statistical difference in SVR rates in the two groups
irrespective of any clinical or virological variables. CONCLUSIONS: In treatment
naive HCV genotype 1 patients, SVR was 95% in those treated for either 8 weeks or
12 weeks with ledipasvir and sofosbuvir. 8 week ledipasvir and sofosbuvir can
reduce costs without compromising outcomes for those patients who qualify for
such regimen.
PMID- 28691378
TI - Coexistence of Low Damping and Strong Magnetoelastic Coupling in Epitaxial Spinel
Ferrite Thin Films.
AB - Low-loss magnetization dynamics and strong magnetoelastic coupling are generally
mutually exclusive properties due to opposing dependencies on spin-orbit
interactions. So far, the lack of low-damping, magnetostrictive ferrite films has
hindered the development of power-efficient magnetoelectric and acoustic
spintronic devices. Here, magnetically soft epitaxial spinel NiZnAl-ferrite thin
films with an unusually low Gilbert damping parameter (<3 * 10-3 ), as well as
strong magnetoelastic coupling evidenced by a giant strain-induced anisotropy
field (~1 T) and a sizable magnetostriction coefficient (~10 ppm), are reported.
This exceptional combination of low intrinsic damping and substantial
magnetostriction arises from the cation chemistry of NiZnAl-ferrite. At the same
time, the coherently strained film structure suppresses extrinsic damping,
enables soft magnetic behavior, and generates large easy-plane magnetoelastic
anisotropy. These findings provide a foundation for a new class of low-loss,
magnetoelastic thin film materials that are promising for spin-mechanical
devices.
PMID- 28691379
TI - Spot diagnosis: Progressive cribriform and zosteriform hyperpigmentation.
PMID- 28691380
TI - Transverse relaxation time constants of the five major metabolites in human brain
measured in vivo using LASER and PRESS at 3 T.
AB - PURPOSE: The goal of this study was to measure and compare the apparent
transverse relaxation time constants (T2 ) of five intracellular metabolites
using localization by adiabatic selective refocusing (LASER) and point-resolved
spectroscopy (PRESS) sequences in the human brain at 3 T. METHODS: Five healthy
subjects were studied at 3 T. 1 H spectra from the prefrontal cortex were
acquired at six different echo times using LASER and PRESS sequences.
Postprocessed data were analyzed with LCModel, and the resulting amplitudes were
fitted using a mono-exponential decay function to determine the T2 of
metabolites. RESULTS: Twenty-one percent higher apparent T2 values for the
singlet resonances of N-acetyl aspartate, total creatine, and total choline were
measured with LASER as compared with PRESS, whereas comparable apparent T2 values
were measured for strongly coupled metabolites, glutamate, and myo-inositol, with
both sequences. CONCLUSIONS: Reliable T2 measurements were obtained with both
sequences for the five major intracellular metabolites. The LASER sequence
appears to be more efficient in suppressing the diffusion component for singlets
(having nonexchangeable protons) compared to J-coupled metabolites. Magn Reson
Med 79:1260-1265, 2018. (c) 2017 International Society for Magnetic Resonance in
Medicine.
PMID- 28691381
TI - Self-Forming Interlocking Interfaces on the Immiscible Polymer Bilayers via
Gelation-Mediated Phase Separation.
AB - Gelation-mediated phase separation is applied to prepare immiscible polymer
bilayer films with an interlocking interface structure. Polymer systems
consisting of copolymer of urea and polydimethylsiloxane and epoxy are selected
to demonstrate the feasibility. When the epoxy fraction exceeds 25 wt%, well
defined bilayer structures self-form by a one-pot casting method in which the
phase separation state is fixed by an evaporation-induced gelation. Microscopy
studies of the resulting bilayers clearly reveal that interlocking structures
form during the bilayer films construct. The interlocking structures lead to an
enhanced interfacial adhesion and higher fracture energy. The current strategy
might offer a facile way to in situ create an interlocking interface between
immiscible polymer systems.
PMID- 28691382
TI - Variation in Prescription Drug Coverage for Triptans: Analysis of Insurance
Formularies.
AB - OBJECTIVES: To analyze triptan coverage by insurers to examine (1) possible
disparities in coverage for different formulations (oral, intranasal, etc) and
(2) quantity limits and stepped care requirements to obtain triptans. BACKGROUND:
Triptans are FDA approved migraine abortive medications. Patients frequently
state that they have difficulty accessing triptans prescribed to them. METHODS:
We searched the 2015 drug formularies of commercial and government health
insurers providing coverage in NY State. We created a spreadsheet with all of the
commercially available triptans and included information about covered
formulations, tier numbers and quantity limits for each drug. We then calculated
the number of listed plans that cover or do not cover each triptan or triptan
formulation, the total number of medications not covered by an insurance provided
across all of its plans, as well as the percentage of plans offered by individual
companies and across all companies that covered each drug. We also calculated the
number and proportion of plans that imposed quantity limits or step therapy for
each drug. RESULTS: Of the 100 formularies searched, generic sumatriptan (all
formulations), naratriptan, and zolmitriptan tablets were covered by all plans,
and rizatriptan tablets and ODTs were covered by 98% of plans. Brand triptans
were less likely to be covered: 4/36 Medicaid plans covered brand triptans.
Commercial insurers were more likely to cover brand triptans. All plans imposed
quantity limits on 1+ triptan formulations, with >80% imposing quantity limits on
14/19 formulations studied. Almost all plans used tiers for cost allocation for
different medications. Generic triptans were almost always in Tier 1. Brand
triptans were most commonly in Tier 3. Approximately 40% of brand triptans
required step therapy, compared with 11% of generic triptans. CONCLUSIONS: There
are substantial variations in coverage and quantity limits and a high degree of
complexity in triptan coverage for both government and commercial plans.
PMID- 28691383
TI - Different origins of two corpora lutea recovered from a pregnant African elephant
(Loxodonta africana).
AB - Elephant ovaries contain multiple corpora lutea (CLs) throughout pregnancy. Two
CLs (P-1 and P-2) collected from a pregnant African elephant were used to
investigate their origin and physiological state in this study. The mRNA
expressions of prolactin receptor, CYP11A and inhibin betaB subunit were higher
in P-2 than in P-1, while LHCGR and inhibin betaA subunit mRNA were higher in P-1
than in P-2. Protein expression of cleaved caspase-3 was detected in P-1 but not
in P-2. These results suggest different origins for the two CLs in this one
pregnant elephant, and we also demonstrated the production of bioactive prolactin
by the elephant placenta.
PMID- 28691384
TI - Vaginectomy and vaginoplasty for isolated vaginal recurrence 8 years after
cervical cancer radical hysterectomy: A case report and literature review.
AB - A subgroup of early-stage cervical cancer patients suffer from vaginal cuff
recurrence following a primary surgery; however, recurrence after a disease-free
interval of 5 years is rare. Treatments for isolated vaginal relapse remain
controversial. Here we report a case of a 50-year-old woman with isolated vaginal
cuff recurrence 8 years after primary radical surgery for cervical cancer. We
conducted a vaginectomy and vaginoplasty using a type of tissue-engineered
biomaterial graft. Three chemotherapy cycles of paclitaxel and cisplatin were
administered after surgery. The patient has no evidence of disease to date (18
months after surgery) and had regained a satisfactory sexual life by 8 months
postoperatively. To our knowledge, this case represents the first report
regarding the use of vaginoplasty with biomaterial graft following vaginectomy
for late isolated vaginal recurrence of cervical cancer in a patient who had
undergone a primary radical hysterectomy.
PMID- 28691385
TI - Injectable loop recorder implantation in an ambulatory setting by advanced
practice providers: Analysis of outcomes.
AB - INTRODUCTION: Implantable loop recorder (ILR) insertion has historically been
performed in a surgical environment such as the electrophysiology (EP) lab. The
newest generation loop recorder (Medtronic Reveal LINQTM, Minneapolis, MN, USA)
is injectable with potential for implantation in a non-EP lab setting by advanced
practice providers (APPs) facilitating improved workflow and resource
utilization. We report the safety and efficacy of injectable ILR placement in the
ambulatory care setting by APPs. METHODS: A retrospective review was performed
including all patients referred for injectable ILR placement from March 2014 to
November 2015. All device placement procedures were performed in an ambulatory
care setting using the standard manufacturer deployment kit with sterile
technique and local anesthetic following a single dose of intravenous
antibiotics. Acute procedural success and complication rates following injectable
ILR placement in the ambulatory setting were reviewed. RESULTS: During the study
period, 125 injectable ILRs were implanted. Acute procedural success with
adequate sensing (R-waves >= 0.2 mV) occurred in 100% of patients. There were no
acute procedural complications. Subacute complications occurred in two patients
(1.6% of implantations), including one possible infection treated with oral
antibiotics and one device removal due to pain at the implant site. CONCLUSION:
In this retrospective single-center study, implantation of injectable ILR in an
ambulatory care setting by APPs following a single dose of intravenous
antibiotics and standard manufacturer technique yielded a low complication rate
with high acute procedural success. Use of this implantation strategy may improve
EP lab workflow while providing a safe and effective technique for device
placement.
PMID- 28691386
TI - Reduced and Surface-Modified Graphene Oxide with Nonlinear Resistivity.
AB - Field-grading materials (FGMs) are used to reduce the probability for electrical
breakdowns in critical regions of electrical components and are therefore of
great importance. Usually, FGMs are heavily filled (40 vol.%) with semi
conducting or conducting particles. Here, polymer-grafted reduced graphene oxide
(rGO) is used as a filler to accomplish percolated networks at very low filling
ratios (<2 vol.%) in a semi-crystalline polymer matrix: poly(ethylene-co-butyl
acrylate) (EBA). Various simulation models are used to predict the percolation
threshold and the flake-to-flake distances, to complement the experimental
results. A substantial increase in thermal stability of rGO is observed after
surface modification, either by silanization or subsequent polymerizations. The
non-linear DC resistivity of neat and silanized rGO and its trapping of charge
carriers in semi-crystalline EBA are demonstrated for the first time. It is shown
that the polymer-grafted rGO improve the dispersibility in the EBA-matrix and
that the graft length controls the inter-flake distances (i.e. charge-carrier
hopping distances). By the appropriate selection of graft lengths, both highly
resistive materials at 10 kV mm-1 and FGMs with a large and distinct drop in
resistivity (six decades) are obtained, followed by saturation. The nonlinear
drop in resistivity is attributed to narrow inter-flake distance distributions of
grafted rGO.
PMID- 28691387
TI - Cascades in Compartments: En Route to Machine-Assisted Biotechnology.
AB - Biological compartmentalization is a fundamental principle of life that allows
cells to metabolize, propagate, or communicate with their environment. Much
research is devoted to understanding this basic principle and to harness
biomimetic compartments and catalytic cascades as tools for technological
processes. This Review summarizes the current state-of-the-art of these
developments, with a special emphasis on length scales, mass transport phenomena,
and molecular scaffolding approaches, ranging from small cross-linkers over
proteins and nucleic acids to colloids and patterned surfaces. We conclude that
the future exploration and exploitation of these complex systems will largely
benefit from technical solutions for the integrated, machine-assisted development
and maintenance of a next generation of biotechnological processes. These goals
should be achievable by implementing microfluidics, robotics, and added
manufacturing techniques supplemented by theoretical simulations as well as
computer-aided process modeling based on big data obtained from multiscale
experimental analyses.
PMID- 28691388
TI - Topical treatment with sacran, a sulfated polysaccharide from Aphanothece sacrum,
improves corneocyte-derived parameters.
AB - Sacran, a polysaccharide isolated from Aphanothece sacrum (Suizenji-nori) alga,
has unique characteristics in terms of its physiological properties and effects
on the skin, and has recently become a focus of attention as a novel biomaterial.
In a previous study, we reported the unique physical characteristics of sacran,
which forms a gel-like film containing water in the presence of polyols. This
film resists penetration by water and chemicals. We expected this unique physical
characteristic to act as an artificial barrier upon the application of sacran to
the skin. In the present study, we tested the efficacy of sacran application in
healthy individuals who reported previous symptoms of dry or inflamed skin, to
evaluate the potential benefits of sacran for skin care in patients with mild
atopic dermatitis. Compared with placebo, sacran-containing serum did not
significantly alter either the water content of the skin surface or
transepidermal water loss. However, subjects using the serum showed improvements
in corneocyte parameters including size, percentage of thick abrasion, ratio of
SH to SS groups, ratio of interleukin (IL)-1 receptor antagonist to IL-1alpha,
and carbonylated protein level. These results indicate that the sulfated
polysaccharide sacran is an effective agent for improving or maintaining the skin
conditions.
PMID- 28691389
TI - Fetal left ventricular non-compaction cardiomyopathy with ascites: A case report.
AB - Here we report a case of fetal left ventricular non-compaction cardiomyopathy
with ascites and cardiac dysfunction at a gestational age of 34+5 weeks.
Laboratory tests did not reveal any sign of viral infection in utero. A female
neonate weighing 2436 g was delivered by emergency cesarean section due to non
reassuring fetal status. Postnatal echocardiography confirmed left ventricular
non-compaction cardiomyopathy with severe cardiac failure. Although she was
treated effectively during the acute period by continuous flow peritoneal
dialysis, surgical ligation of a patent ductus arteriosus, and inhaled nitric
oxide, she died on day 41 of life. Symptoms of severe cardiac dysfunction
appeared antenatally in this patient and the outcome was poor.
PMID- 28691390
TI - An improved digital polymerase chain reaction protocol to capture low-copy KRAS
mutations in plasma cell-free DNA by resolving 'subsampling' issues.
AB - Genetic alterations responsible for the initiation of cancer may serve as
immediate biomarkers for early diagnosis. Plasma levels of cell-free DNA (cfDNA)
in patients with cancer are higher than those in healthy individuals; however,
the major technical challenge for the widespread implementation of cfDNA
genotyping as a diagnostic tool is the insufficient sensitivity and specificity
of detecting early-stage tumors that shed low amounts of cfDNA. To establish a
protocol for ultrasensitive droplet digital polymerase chain reaction (ddPCR) for
quantification of low-frequency alleles within a limited cfDNA pool, two-step
multiplex ddPCR targeting eight clinically relevant mutant KRAS variants was
examined. Plasma samples from patients with colorectal (n = 10) and pancreatic
cancer (n = 9) were evaluated, and cfDNA from healthy volunteers (n = 50) was
utilized to calculate reference intervals. Limited cfDNA yields in patients with
resectable colorectal and pancreatic cancers did not meet the requirement for
efficient capture and quantification of rate mutant alleles by ddPCR. Eight
preamplification cycles followed by a second-run ddPCR were sufficient to obtain
approximately 5000-10 000 amplified copies per ng of cfDNA, resolving the
subsampling issue. Furthermore, the signal-to-noise ratio for rare mutant alleles
against the extensive background presented by the wild-type allele was
significantly enhanced. The cutoff limit of reference intervals for mutant KRAS
was determined to be ~ 0.09% based on samples from healthy individuals. The
modification introduced in the ddPCR protocol facilitated the quantification of
low-copy alleles carrying driver mutations, such as oncogenic KRAS, in localized
and early-stage cancers using small blood volumes, thus offering a minimally
invasive modality for timely diagnosis.
PMID- 28691391
TI - Abnormal Pressure-Induced Photoluminescence Enhancement and Phase Decomposition
in Pyrochlore La2 Sn2 O7.
AB - La2 Sn2 O7 is a transparent conducting oxide (TCO) material and shows a strong
near-infrared fluorescent at ambient pressure and room temperature. By in situ
high-pressure research, pressure-induced visible photoluminescence (PL) above 2
GPa near 2 eV is observed. The emergence of unusual visible PL behavior is
associated with the seriously trigonal lattice distortion of the SnO6 octehedra,
under which the Sn-O1-Sn exchange angle theta is decreased below 22.1 GPa, thus
enhancing the PL quantum yield leading to Sn 3 P1 -> 1 S0 photons transition.
Besides, bandgap closing followed by bandgap opening and the visible PL appearing
at the point of the gap reversal, which is consistent with high-pressure phase
decomposition, are discovered. The high-pressure PL results demonstrate a well
defined pressure window (7-17 GPa) with flat maximum PL yielding and sharp edges
at both ends, which may provide a great calibration tool for pressure sensors for
operation in the deep sea or at extreme conditions.
PMID- 28691392
TI - Metal-Free Nitrogen-Doped Mesoporous Carbon for Electroreduction of CO2 to
Ethanol.
AB - CO2 electroreduction is a promising technique for satisfying both renewable
energy storage and a negative carbon cycle. However, it remains a challenge to
convert CO2 into C2 products with high efficiency and selectivity. Herein, we
report a nitrogen-doped ordered cylindrical mesoporous carbon as a robust metal
free catalyst for CO2 electroreduction, enabling the efficient production of
ethanol with nearly 100 % selectivity and high faradaic efficiency of 77 % at
0.56 V versus the reversible hydrogen electrode. Experiments and density
functional theory calculations demonstrate that the synergetic effect of the
nitrogen heteroatoms and the cylindrical channel configurations facilitate the
dimerization of key CO* intermediates and the subsequent proton-electron
transfers, resulting in superior electrocatalytic performance for synthesizing
ethanol from CO2 .
PMID- 28691393
TI - Sequence and Architectural Control in Glycopolymer Synthesis.
AB - Glycopolymers are synthetic-carbohydrate-containing materials capable of
interacting and binding to specific targeting lectins, which are crucially
important in many biologically active processes. Over the last decade, advances
in synthetic chemistry and polymerization techniques have enabled the development
of sequence and architecturally controlled glycopolymers for different types of
bioapplications, such as drug delivery and release purposes, gene therapy, lectin
based biosensors, and much more in the future. These precision glycopolymers are
able to mimic structural and functional features of the naturally existing
glycocalyx. Furthermore, self-assembled glycopolymers could enhance specific and
selective recognition properties on multivalent scaffolds in glycoscience. This
mini-review will focus on production methods and recent advances in precision
synthesis and self-assembly of glycopolymers. Additionally, possible
contributions of single-chain folding in glycopolymers will be discussed as a
future prospect.
PMID- 28691394
TI - A new HLA-A allele, HLA-A*30:62, sequenced in a Chinese individual.
AB - HLA-A*30:62 has one nucleotide change from HLA-A*30:01:01 where 311 Threonine
(ACC) is changed to Asparagine (AAC).
PMID- 28691395
TI - Low expression of soluble human leukocyte antigen G in early gestation and
subsequent placenta-mediated complications of pregnancy.
AB - AIM: Abnormal placentation is a common pathogenic mechanism of many placenta
mediated complications of late pregnancy, including pre-eclampsia, fetal growth
restriction, stillbirth, and placental abruption. During successful placentation,
the trophoblast (which is a semi-allograft) is not rejected by decidual immune
cells because of maternal immune tolerance, mainly induced by human leukocyte
antigen G (HLA-G). Deficient HLA-G expression seems to be associated with the
development of complications of pregnancy. The aim of this study was to determine
whether low soluble HLA-G (sHLA-G) levels in maternal blood at the beginning of
pregnancy may be associated with subsequent placenta-mediated complications.
METHODS: For this retrospective case-control study, 117 cases of placenta
mediated complications of pregnancy and 234 controls with uneventful pregnancy
were selected. Plasma sHLA-G levels were measured at 11-13 weeks' gestation by
the enzyme-linked immunosorbent assay method in blood samples previously obtained
at first-trimester prenatal screening for chromosomal fetal abnormalities.
RESULTS: Women who subsequently developed placenta-mediated complications had
significantly lower sHLA-G levels at the beginning of pregnancy (median, 43.08
IU/mL) than controls (median, 49.10 IU/mL; P = 0.008). An sHLA-G level lower than
43.50 IU/mL at the end of the first trimester was associated with a twofold
increased risk of developing a pregnancy complication (odds ratio, 1.82; 95%
confidence interval, 1.22-2.73). The strongest association, although only
moderately strong, was observed with severe pre-eclampsia (odds ratio, 2.66; 95%
confidence interval, 1.08-6.56). CONCLUSION: Placenta-mediated complications of
pregnancy may be associated with low sHLA-G levels in the first trimester,
suggesting a potential role of sHLA-G in the early stages of placentation.
PMID- 28691396
TI - Tuning the Selectivity of Catalytic Carbon Dioxide Hydrogenation over
Iridium/Cerium Oxide Catalysts with a Strong Metal-Support Interaction.
AB - A one-step ligand-free method based on an adsorption-precipitation process was
developed to fabricate iridium/cerium oxide (Ir/CeO2 ) nanocatalysts. Ir species
demonstrated a strong metal-support interaction (SMSI) with the CeO2 substrate.
The chemical state of Ir could be finely tuned by altering the loading of the
metal. In the carbon dioxide (CO2 ) hydrogenation reaction it was shown that the
chemical state of Ir species-induced by a SMSI-has a major impact on the reaction
selectivity. Direct evidence is provided indicating that a single-site catalyst
is not a prerequisite for inhibition of methanation and sole production of carbon
monoxide (CO) in CO2 hydrogenation. Instead, modulation of the chemical state of
metal species by a strong metal-support interaction is more important for
regulation of the observed selectivity (metallic Ir particles select for methane
while partially oxidized Ir species select for CO production). The study provides
insight into heterogeneous catalysts at nano, sub-nano, and atomic scales.
PMID- 28691397
TI - Cyanidin-3-glucoside increases whole body energy metabolism by upregulating brown
adipose tissue mitochondrial function.
AB - SCOPE: Obesity develops when energy intake exceeds energy expenditure. Promoting
brown adipose tissue (BAT) formation and function increases energy expenditure
and may protect against obesity. Cyanidin-3-glucoside (C3G) is an anthocyanin
compound that occurs naturally in many fruits and vegetables. In this study, we
investigated the effect and mechanism of C3G on the prevention of obesity.
METHODS AND RESULTS: Db/db mice received C3G dissolved in drinking water for 16
wk; drinking water served as the vehicle treatment. The total body weight, energy
intake, metabolic rate, and physical activity were measured. The lipid droplets,
gene expression and protein expression were evaluated by histochemical staining,
real-time PCR, and western blots. We found that C3G increased energy expenditure,
limited weight gain, maintained glucose homeostasis, reversed hepatic steatosis,
improved cold tolerance, and enhanced BAT activity in obese db/db mice. C3G also
induces brown-like adipocytes (beige) formation in subcutaneous white adipose
tissue (sWAT) of db/db mice model. We also found that C3G potently regulates the
transcription of uncoupling protein 1 (UCP1) both in BAT and sWAT through
increasing mitochondrial number and function. CONCLUSION: Our results suggest
that C3G plays a role in regulating systemic energy balance, which may have
potential therapeutic implications for the prevention and control of obesity.
PMID- 28691398
TI - Discovery of a novel HLA-B*07 variant, HLA-B*07:294, in a Chinese individual.
AB - The novel HLA-B*07:294 allele differs from the closest matching allele, HLA
B*07:02:01 by 1 nucleotide substitution.
PMID- 28691399
TI - Global patterns and clines in the growth of common carp Cyprinus carpio.
AB - This review provides a meta-analytical assessment of the global patterns and
clines in the growth of Cyprinus carpio as measured by length-at-age (Lt ) or von
Bertalanffy growth function (VBGF) parameters, mass-length relationship (W-Lt )
and condition factor, based on literature data. In total, 284 studies were
retrieved spanning 91 years of research and carried out on 381 waterbodies
locations in 50 countries in all five continents. Although native C. carpio
achieved larger (asymptotic) size relative to its non-native counterpart, the
latter grew faster during the first 7 years of life. Lentic populations
(especially in natural lakes) also achieved larger sizes relative to lotic ones
and the same was true for populations in cold and temperate v. arid climates.
Unlike previous studies (on much more restricted datasets), only weak latitudinal
clines in instantaneous growth rate, Lt at age 3 and mortality were observed
globally and this was probably due to the presence of counter-gradient growth
variation at all representative age classes (i.e. 1-10 years). Slightly negative
allometry was revealed by the W-Lt and the related form factor tended to
distinguish the more elongated and torpedo-shaped body typical of the wild form
from the deeper body of feral-domesticated C. carpio. Existing population
dynamics models for C. carpio will benefit from the comprehensive range of
waterbody type * climate class-specific VBGF parameters provided in the present
study; whereas, more studies are needed on the species' growth in tropical
regions and to unravel the possibility of confounding effects on age estimation
due to both historical and methodological reasons.
PMID- 28691400
TI - Effect of size on spawning time in the lesser sandeel Ammodytes marinus.
AB - Ovarian development was examined in relation to size and temperature in late pre
spawning Ammodytes marinus over 5 years. Oocyte diameter was positively related
to length indicating that larger females spawned earlier. Age and temperature,
whilst accounting for the effect of length, were not found to affect oocyte
development, although the thermal range examined was only 1.3 degrees C.
PMID- 28691401
TI - Interannual variability in reproductive traits of the Patagonian toothfish
Dissostichus eleginoides around the sub-Antarctic island of South Georgia.
AB - Commercial fisheries data, collected as part of an observer programme and
covering the period 1997-2014, were utilized in order to define key reproductive
traits and spawning dynamics of the Patagonian toothfish Dissostichus eleginoides
at South Georgia. Multi-year spawning site fidelity of D. eleginoides was
revealed through the identification of previously unknown spawning hotspots.
Timing of female spawning was shown to have shifted later, leading to a shorter
spawning duration. A decrease in length and mass of female and male spawning fish
and a reduced number of large spawning fish was found, evidence of a change in
size structure of spawning D. eleginoides. During the study period fewer later
maturity stage females (including spawning stage) were observed in conjunction
with increased proportions of early stage female D. eleginoides. The findings are
discussed in the context of reproductive success, with consideration of the
possible effects such spawning characteristics and behaviours may have on egg and
larval survival. This work presents the first long-term assessment of D.
eleginoides spawning dynamics at South Georgia and provides valuable knowledge
for both the ecology of the species and for future fisheries management of this
commercially important species.
PMID- 28691402
TI - Osmolality and blood pressure stability during hemodialysis.
AB - Homeostatic regulation of plasma osmolality (POsm) is critical for normal
cellular function in humans. Arginine vasopressin (AVP) is the major hormone
responsible for the maintenance of POsm and acts to promote renal water retention
in conditions of increased POsm. However, AVP also exerts pressor effects, and
its release can be stimulated by the development of effective arterial blood
volume depletion. Patients with end-stage renal disease on hemodialysis,
particularly those with minimal or no residual renal function, have impaired
ability to regulate water retention in response to AVP. While hemodialysis can
assist with this task, patients are subject to relatively rapid shifts in volume
and electrolytes during the procedure. This can result in the development of
transient osmotic gradients that lead to the movement of water from the
extracellular to the intracellular space. Hypotension may result-both as a
consequence of water movement out of the intravascular compartment, but also from
impaired AVP release and inadequate vascular tone. In this review, we explore the
evidence for POsm changes during hemodialysis, associations with adverse
outcomes, and methods to minimize the rapidity of changes in POsm in an effort to
reduce patient symptoms and minimize intra-dialytic hypotension.
PMID- 28691403
TI - Effects of Davallia formosana Hayata Water and Alcohol Extracts on Osteoblastic
MC3T3-E1 Cells.
AB - The Taiwanese native fern Davallia formosana Hayata (DFH) is used to treat bone
diseases in classical Chinese medicine. We analyzed MC3T3E1 osteoblasts treated
with different concentrations of water and ethanol extracts (10, 25, and 50
[both], and 100 MUg/mL [DFE only]) using cell viability, expression of osteoblast
differentiation markers [bone morphogenetic protein 2 (BMP-2), collagen 1 (CoL
1), alkaline phosphatase (ALP), and Runt-related transcription factor 2 (Runx
2)], and mineralization. These were significantly increased by DFW or DFE after
24-h incubation compared with the untreated controls. Compared with other
treatments, DFW 50 and DFE 100 MUg/mL significantly increased MC3T3E1 cell
survival. DFW 25 and 50 MUg/mL increased bone BMP-2, CoL-1, ALP, and Runx2
protein expression, ALP activity, and mineralization more than DFE did. Repeated
chromatographic separation of DFW yielded compound (-)-epicatechin-3-O-d
allipyranoside (ECAP), which was characterized using 1 H and 13 C nuclear
magnetic resonance spectroscopy. (-)-Epicatechin-3-O-d-allipyranoside (0.01
MUg/mL) significantly increased cell survival (118.9%) and mineralization
(218.7%) compared with that of the control treatment. We inferred that ECAP could
mediate the main activity of DFW in bone formation, likely through BMP-2-induced
Runx2 transcription, which increased bone cell differentiation factors ALP and
CoL-1 and promoted mineralization. (-)-Epicatechin-3-O-d-allipyranoside could be
an anti-osteoporotic agent. Copyright (c) 2017 John Wiley & Sons, Ltd.
PMID- 28691404
TI - 'Delisting' OxyContin(r) to reduce prescription opioid-related harms in Ontario
(Canada)-gauging effects 5 years later.
PMID- 28691405
TI - Significance of pathological examination of the placenta, with a focus on
intrauterine infection and fetal growth restriction.
AB - Chorioamnionitis (CAM) is associated with abortion, premature labor and neonatal
disorders. In this condition, precise pathological diagnosis of the placenta is
very important. Besides histological examination, macroscopic examination of the
placenta is indispensable. Diagnostic points and complications of CAM are
emphasized in this paper. Blanc's classification (revised by Nakayama) is
introduced for the accurate determination of CAM stage. Principles of
classification based on the causes of fetal growth restriction (FGR) (mainly
resulting from placental pathology) are also described. Children born with FGR
have high disease-related morbidity. In these cases, placental examination can be
a useful prognostic tool. Placental pathology is associated not only with the
underlying cause of FGR, but also with infant prognosis.
PMID- 28691406
TI - A Flow Cytometry-based Method for the Screening of Nanomaterial-induced Reactive
Oxygen Species Production in Leukocytes Subpopulations in Whole Blood.
AB - To date, the use and translation of nanomedicine from the laboratory to the
clinic has been relatively slow. Among other issues, one of the reasons for this
tardiness is the lack of the availability of quick and reliable toxicity tools
for the screening of nanomaterials (NMs). In this investigation, we apply a flow
cytometry-based method for the detection of nanomaterial-induced oxidative stress
by measurement of reactive oxygen species production in specific leukocyte
subpopulations in human whole blood. The screening of a panel of relevant
nanomedical-associated materials (liposomes, silica, iron oxide and
functionalized single-walled carbon nanotubes) demonstrated that only the carbon
nanotubes induced oxidative stress in human circulating leukocytes. In summary,
we apply and corroborate a flow cytometry-based method for the simple and
effective measurement of NM-induced oxidative stress in human blood
subpopulations after realistic and relevant exposure scenarios which is extremely
useful in future toxicological applications.
PMID- 28691407
TI - Oxidative stress, hepcidin and nesfatin-I status in childhood iron and vitamin
B12 deficiency anemias.
AB - BACKGROUND: Anemia is a disease that is long and often repetitive and can result
in a great burden to the national economy. The most frequent nutritional
deficiency anemias in children are related with iron and vitamin B12
deficiencies. OBJECTIVES: The aim of this study was to determine the oxidative
stress, hepcidin, and nesfatin-I levels in childhood iron and vitamin B12
deficiency anemias. MATERIAL AND METHODS: The study had 3 groups of 15 children,
iron anemia deficiency group, vitamin B12 deficiency group and a control group.
RESULTS: The TBARS and nesfatin-I levels were significantly higher in the iron
and vitamin B12 deficiency groups and the total antioxidant levels were
significantly lower when compared to the control group. In contrast, the plasma
hepcidin levels were significantly lower in the iron deficiency group (p < 0.01)
when compared to the control group; however, no significant differences were
observed in the vitamin B12 deficiency group. Plasma homocysteine levels were
significantly higher in the vitamin B12 deficiency group when compared to the
control group (p < 0.001), but no differences were determined between the iron
deficiency and control groups. CONCLUSIONS: Our results showed that there are
high levels of oxidative stress in childhood iron and vitamin B12 deficiency
anemias, and we propose that plasma hepcidin and homocycteine levels may be
useful in the differential diagnosis of childhood nutritional deficiency anemias.
Nesfatin-1 hormone levels were identified for the first time in childhood iron
deficiency and vitamin B12 deficiency anemias within this study and this hormone
may also be useful in the differential diagnosis of anemias.
PMID- 28691408
TI - The role of CD36 receptor in the pathogenesis of atherosclerosis.
AB - Atherosclerosis is a progressive, chronic inflammation in artery walls. Oxidized
low density lipoproteins (ox-LDL) play an important role in atherosclerotic
plaque formation. ox-LDL are taken up by macrophages mainly through scavenger
receptors, among which CD36 is considered to be the most important. Animal
studies have shown that crossing atherogenic mice with a strain lacking the
expression of CD36 prevented the development of atherosclerosis despite a diet
rich in saturated LCFA. In humans, autopsy studies performed in obese patients
have demonstrated increased expression of CD36 receptor on macrophages, comprised
within atherosclerotic plaques. Until recently it had been believed that CD36 is
a major player in atherosclerosis progression in humans. However, recent studies
challenge this conviction, showing increased incidence of coronary heart disease
in the subgroup of patients with decreased expression of CD36. This article
reviews the role of CD36 receptor in the development of atherosclerosis. The
authors also discuss current possibilities to interfere with CD36, their
potential benefits and hazards.
PMID- 28691409
TI - Comparison of titanium cable tension band and nickel-titanium patella
concentrator for patella fractures.
AB - BACKGROUND: Patellar fractures account for approximately 1% of all fractures. Due
to the patella's importance as regards the extensor mechanism, effort should be
made to preserve the patella. Several operative treatment methods have been
introduced for patella fractures. OBJECTIVES: This study aims to compare the
clinical effect of a titanium cable tension band and nickeltitanium (NiTi)
patella concentrator (NT-PC) in treating patella fractures. MATERIAL AND METHODS:
Thirty-nine patients with patella fractures were enrolled in this retrospective
study. All the patients were treated via the open reduction internal fixation
procedure using a titanium cable tension band or NT-PC. All the patients were
followed up over an average period of 13 months. The main outcome measures were
operation time, time of fracture union, postoperative complications, and Bostman
knee scores. Statistical analyses were conducted between the 2 groups. RESULTS:
All the patients were operated on successfully. The operation time of the NT-PC
treatment group was less than that of the titanium cable tension band treatment
group (p < 0.05). The mean scores at the final follow-up were 28.2 and 27.6
points in the titanium cable tension band and NT-PC groups, respectively. No
significant difference was observed between the excellent and good results (p >
0.05). CONCLUSIONS: Both titanium cable tension band and NT-PC showed good
efficacy for the treatment of patellar fractures. NT-PC fixation, a new option
for the treatment of patella fractures, is a simple and effective fixation
method.
PMID- 28691410
TI - The risk of plasma vitamin A, C, E and D deficiency in patients with metabolic
syndrome: A case-control study.
AB - BACKGROUND: The increasing incidence of metabolic diseases such as obesity or
diabetes have made them a major public health problem. Increasing oxidative
stress induced by reactive oxygen species, which initiate the oxidative adverse
changes in the cell, is mentioned, among other risk factors, to underlie these
diseases. Vitamin A, C and E are listed among the non-enzymatic mechanisms
counteracting this phenomenon. Vitamin D deficiency is also associated with
cardiovascular diseases. OBJECTIVES: The aim of the study was to assess the risk
of vitamin A, C, E and D deficit in the plasma of metabolic syndrome (MS)
patients. MATERIAL AND METHODS: The study included 191 patients with MS and 98
subjects without MS. Loglinear analysis was used in the assessment of mutual
interactions between the vitamin concentration and the analysis of classification
by ROC curves to predict the frequency of vitamin deficiency in MS patients.
RESULTS: A correlation was found between the plasma level of vitamins in the
group of MS patients. Vitamin A concentration correlated with that of vitamin C
(r = 0.51, p = 0.0000), vitamin D (r = 0.49, p = 0.0000) and E (r = 0.32, p =
0.0001). The plasma level of vitamin D correlated with the level of vitamin E (r
= 0.46, p = 0.00000) and vitamin C (r = 0.37, p = 0.0000). Regression analysis
showed a correlation between the concentration of the tested vitamins in patients
with MS. Interactions were observed between vitamins C and A and between C and D.
HDL cholesterol level was lower in patients with vitamin A deficiency compared to
patients with its normal level. CONCLUSIONS: The plasma levels of vitamin A, C, E
and D were significantly lower in patients with MS than in healthy subjects and
they mutually correlated with each other. The normalization of glucose and HDL
level may contribute to the regulation of the concentration of vitamin A in
patients with MS.
PMID- 28691411
TI - Kupffer cells in immune activation and tolerance toward HBV/HCV infection.
AB - Kupffer cells (KCs) are macrophages that are found in the sinusoids of the liver.
KCs are a crucial part of the innate immune system, acting as scavengers and
phagocytes. KCs and sinusoidal endothelial cells together form the first immune
barrier of the portal system. Studies show that KCs can not only maintain
homeostasis in the immune response, but also facilitate the pathogenesis of type
B and type C hepatitis (HBV/HCV) through their antigen-presenting function and
secretion of soluble mediators. KCs can express toll-like receptors (TLRs), Fas
ligand (FasL) and programmed cell death ligand 1 (PD-L1), and secrete large
amounts of inflammatory factors leading to immune tolerance toward HBV/HCV. On
the one hand, KCs contribute to the clearance of HBV/HCV due to their nature as
innate immune cells. At the same time, KCs induce immune tolerance toward
HBV/HCV, which leads to chronicity of the infection. The dual role of KCs in the
immune response toward HBV/HCV means it is a gigantic challenge for scientists to
illuminate the detailed mechanisms involved, but it also offers important
potential therapeutic targets.
PMID- 28691412
TI - Rehabilitation in multiple sclerosis.
AB - The aim of the study is to present a strategy of rehabilitation in multiple
sclerosis on the basis of the latest developments in the field of physiotherapy.
The publications on the problem discuss a wide range of methods of physiotherapy
that can be used in order to reduce the degree of disability and alleviate the
symptoms associated with the disease. The complexity of the disease, the
difficulty in determining the appropriate treatment and a wide range of symptoms
require a comprehensive approach to the patient, which would include both
pharmacology and neurorehabilitation. Rehabilitation, which includes
psychotherapy and symptomatic therapy, is regarded nowadays as the best form of
treatment for multiple sclerosis. An indepth diagnostic assessment of functional
status and prognosis should be carried out before the start of the rehabilitation
process. The prognosis should take into account the mental state, the
neurological status and the awareness of the patient. The kinesiotherapy program
in multiple sclerosis is based on a gradation of physiotherapy which assumes a
gradual transition from basic movements to more complex ones till global
functions are obtained. The most appropriate form of treatment is functional
rehabilitation combined with physical procedures. Recent reports indicate the
need for aerobic training to be included in the rehabilitation program. The
introduction of physical activities, regardless of the severity of the disease,
will reduce the negative effects of akinesia, and thus increase the functional
capabilities of all body systems.
PMID- 28691413
TI - Diagnostic challenges in celiac disease.
AB - Diagnosis of celiac disease in adults is currently based on serologic tests in
combination with histopathological assessment of small intestinal biopsy
specimens. High titers of celiac-specific antibodies in immunocompetent patients
with villous atrophy in a good quality biopsy sample allow us to state a
confident diagnosis. The relief of symptoms and histological improvement after
embarking on a gluten free diet further support the initial diagnosis. However,
in some cases, these conditions are not fulfilled, which requires a critical
evaluation of laboratory and histopathology results and a consideration of other
potential causes for the observed pathologies. To avoid diagnostic uncertainty,
both biopsy and laboratory testing should be performed on a diet containing
gluten. Immune deficiency, cross reaction of antibodies and possibilities of
seronegative or latent celiac disease should be considered while evaluating
serology results. Uneven distribution and variable intensity of histopathological
changes in the small intestine along with multiple disorders presenting a similar
specimen image may lead to invalid biopsy results. Additional laboratory testing
and careful examination of a patient's history may deliver important data for a
differential diagnosis and a more specific biopsy evaluation. Persistence or
recurrence of symptoms, despite the ongoing treatment, requires a revision of the
initial diagnosis, an evaluation of the gluten free diet and a search for
concurrent disorders or complications.
PMID- 28691414
TI - Serum levels of vascular endothelial growth factor and basic fibroblast growth
factor in children with brain tumors.
AB - BACKGROUND: Angiogenesis is the process of new vessel formation originating from
the existing vascular network. It plays an important role in the growth and
spread of malignancies, including brain tumors. The process of angiogenesis is
characterized by increased expression of vascular endothelial growth factor
(VEGF) and basic fibroblast growth factor (bFGF), and by the release of their
soluble forms into circulation. OBJECTIVES: The aim of the study was to evaluate
serum levels of VEGF and bFGF in children with malignant and benign brain tumors.
MATERIAL AND METHODS: The study group (group N) included 106 children diagnosed
with brain tumors. The children in group N were classified according to tumor
pathology into 3 subgroups: N1 (n = 63): patients with malignant tumors,
excluding anaplastic astrocytoma (AA) and glioblastoma multiforme (GBM); N2 (n =
25): patients with benign tumors; and N3 (n = 18): patients with high grade
gliomas (AA and GBM). VEGF and bFGF were determined by ELISA in blood samples
before the initiation of chemotherapy. VEGF and bFGF levels were compared within
the subgroups in relation to tumor grading and the extent of surgery. RESULTS:
The median VEGF in patients with brain tumors was significantly higher than in
the control group. The median levels of VEGF and bFGF in subgroup N1 were
significantly higher than in the control group. The differences in VEGF and bFGF
concentrations between the subgroups in relation to the extent of tumor resection
were not significant. CONCLUSIONS: Significantly higher plasma VEGF levels in
children with brain neoplasms may reflect enhanced angiogenesis in the tumors.
PMID- 28691415
TI - Association of ACE, VEGF and CCL2 gene polymorphisms with Henoch-Schonlein
purpura and an evaluation of the possible interaction effects of these loci in
HSP patients.
AB - BACKGROUND: Henoch-Schonlein purpura (HSP) is a multisystem, small vessel,
leucocytoclastic vasculitis. It is predominantly a childhood vasculitis, rarely
reported in adults. Studies have shown that several different genetic factors
such as genes involved in inflammatory system and renin-angiotensin system (RAS)
are important in the pathogenesis of Henoch-Schonlein purpura. OBJECTIVES: The
purpose of this study was to evaluate the independent effect of 3 gene
polymorphisms including CCL2-2518 C/T, VEGF-634G/C and ACE(I/D) with HSP disease
and their possible joint interactions in developing the disease. MATERIAL AND
METHODS: In this case-control study 47 HSP cases and 74 unrelated healthy
controls were enrolled for evaluation. All individuals were genotyped for CCL2
2518C/T, VEGF-634G/C and ACE(I/D) gene polymorphisms. The possible association of
these polymorphisms with susceptibility to develop HSP disease independently and
in different joint combinations was evaluated. RESULTS: The frequencies of TT
genotype and T allele of CCL2-2518C/T gene polymorphism and CC genotype and C
allele of VEGF-634G/C gene polymorphism were significantly high in HSP children
(p-values = 0.005 and = 0.007 respectively). Interestingly, studying the joint
interaction of these 2 genotypes (CC genotype of VEGF G-634C and TT genotype of
CCL2 C-2518T) in this cohort showed a more significant effect in the development
of the disease (p < 0.000, OR = 6.009). The frequency of TT genotype of CCL2 gene
when combined with II genotype of ACE gene in HSP children was significantly
higher (p < 0.000, OR = 4.213). CONCLUSIONS: The results of this pilot study
provide evidence of the possible gene-gene interaction effects of CCL2, VEGF and
ACE genes in developing HSP disease.
PMID- 28691416
TI - The relationship between major depressive disorder and glucose parameters: A
cross-sectional study in a Chinese population.
AB - BACKGROUND: Depressive symptoms have been linked with insulin resistance in
middle-aged and elderly populations. A strong relationship between peripheral
insulin resistance and glucose homeostasis imbalance has been well established in
previous studies. The role of serum fructosamine and fasting blood glucose (FBG)
in elevating glucose homeostasis has been documented in the literature.
OBJECTIVES: The aim of the study was to examine the association of serum
fructosamine and FBG with major depressive disorder (MDD). MATERIAL AND METHODS:
The study analyzed the clinical characteristics and biochemical parameters of 305
patients with MDD and 312 healthy individuals. RESULTS: Serum concentrations of
lipoprotein-cholesterol (HDL-C), total protein (TP) and creatinine (Cr) were
found to be significantly different between the two groups. Serum fructosamine
and fasting blood glucose (FBG) concentrations were high in patients with MDD
compared with healthy individuals (2.3 +/- 0.26 vs. 2.1 +/- 0.27, p = 0.018; 4.7
+/- 0.45 vs. 4.5 +/- 0.45, p < 0.001). The levels of serum fructosamine and FBG
were also significantly higher in patients with MDD when all participants were
stratified by gender. Age was found to be positively correlated with FBG, serum
fructosamine and Cr (r = 0.203, p < 0.001; r = 0.129, p = 0.025; r = 0.129, p =
0.024), and negatively correlated with TP (r = -0.114, p = 0.047) in patients
with MDD. However, there were no correlations between age and FBG, serum
fructosamine or Cr in the healthy controls. In a multivariate logistic regression
analysis, increased serum fructosamine and FBG concentrations were positively
associated with MDD independently of age and gender, after adjustment for age and
potential confounding factors (OR = 6.313, CI95 %:2.953-13.393, p < 0.001; OR =
2.251, CI95 %: 1.464-3.462, p < 0.001). CONCLUSIONS: The study results suggest
that increased serum fructosamine and FBG concentrations are associated with
depressive conditions, which may influence glucose metabolism and impair glucose
homeostasis in patients with MDD.
PMID- 28691417
TI - Effect of endovascular coronary low-level laser therapy during angioplasty on the
release of endothelin-1 and nitric oxide.
AB - BACKGROUND: Nitric oxide (NO) and endothelin-1 are potentially significant
factors contributing to the pathogenesis of post-angioplasty restenosis. It may
be postulated that low-level laser therapy (LLLT) can favorably influence the
process of restenosis by affecting those factors. OBJECTIVES: The aim of the
study was to evaluate the effect of LLLT applied during percutaneous coronary
intervention (PCI) on the factors participating in the homeostasis of vascular
tone - NO and endothelin-1. MATERIAL AND METHODS: In a randomized, prospective
study of 52 subjects undergoing PCI, an additional 808 nm intravascular LLLT was
applied at a dose of 9 J/cm2 in the lesion part. The control group was 49
subjects with PCI only. We assessed the concentration of nitrites/nitrates
reflecting NO metabolism as well as endothelin-1 in both groups before PCI, and
at 6 h, 12 h and 1 month after the procedure. In addition, half a year after PCI,
a follow-up angiography was performed. RESULTS: Statistically higher
nitrite/nitrate concentrations were observed in the laser group as compared to
the control group in all tests except the pre-PCI assays. Endothelin-1 levels
were significantly higher in the laser group 6 h after PCI with a significant
decrease in subsequent tests, which was not observed in the control group. The
restenosis rate was 15.0% in the laser group and 32.4% in the control group
(however the difference was not statistically significant). CONCLUSIONS: LLLT
applied during the PCI procedure can influence the process of restenosis by
modifying NO and endothelin-1 concentrations.
PMID- 28691418
TI - Associations between the number of natural teeth and the maternal age at
childbirth or history of parity in postmenopausal women: The 2010-2012 Korea
national health and nutrition examination survey.
AB - BACKGROUND: The relationship between reproductive factors, including pregnancy
and delivery, and the number of teeth in postmenopausal women remains to be
revealed. OBJECTIVES: The aim of this study was to evaluate the relationship
between age at first and last delivery, parity and the number of natural teeth in
postmenopausal women, using nationally representative data. MATERIAL AND METHODS:
Data from the Korea National Health and Nutrition Examination Survey between 2010
and 2012 were used, and the analysis in this study was confined to a total of
4,060 respondents who had gone through menopause and had no missing values for
the reproductive factors and outcome variables. The total number of natural teeth
was then calculated after excluding third molars, and frequency of tooth brushing
was recorded as oral health behavior. Univariate and multivariate logistic
regression analyses were used to assess the associations between the number of
natural teeth and reproductive factors. RESULTS: Both a woman's age at her last
childbirth and the number of pregnancies had statistically significant effects on
the number of natural teeth remaining after menopause. With each one-year
increase of age at a woman's last delivery, the number of natural teeth decreased
by a value of 0.12 (p < 0.05). Similar trends were seen with increases in parity,
which resulted in decreases in the number of natural teeth by 0.65 (p < 0.05).
The odds ratios of the percentage of individuals with a 20 or fewer teeth tended
to increase with increases in the woman's age at her last childbirth.
CONCLUSIONS: This study identified an association between the number of natural
teeth and a woman's age at her last childbirth as well as between the number of
natural teeth and parity. Higher ages at last childbirth and higher parity were
found to be potential risk indicators for tooth loss in postmenopausal women.
PMID- 28691419
TI - Circulating PCSK9 affects serum LDL and cholesterol levels more than SREBP-2
expression.
AB - BACKGROUND: Cholesterol homeostasis is dependent upon the sterol regulatory
element binding protein 2 (SREBP-2) regulatory system and the functioning of
plasma proprotein convertase subtilisin/kexin type 9 (PCSK9). Many studies have
also reported that low density lipoprotein receptor (LDLR) levels in cellular
membranes are related to the functioning of these proteins. OBJECTIVES: The aim
of this study was to investigate the association of lipid profiles with
circulating PCSK9 protein values and SREBP-2 expression levels in normal
subjects. MATERIAL AND METHODS: The study involved 120 randomly chosen healthy
subjects. Their lipid profiles were measured using routine laboratory techniques,
and the plasma PCSK9 protein and SREBP-2 expression levels were determined by
ELISA and real time quantitative PCR methods, respectively. A statistical
analysis was carried out using a statistical software package. RESULTS: Linear
regression analyses showed a significant correlation between total cholesterol
and PCSK9 (3.54 +/- 1.31 ng/mL), as well as between total cholesterol and SREBP-2
(0.1-35.38) (p = 0.002 and p = 0.02, respectively). Furthermore, multiple
regression analyses showed strict correlations between PCSK9 and cholesterol
related parameters especially the total cholesterol/HDL-C ratio (beta = 3.53, p =
0.001). There was no significant correlation between circulating PCSK9 and SREBP
2 expression levels (r = 1.2, p = 0.3). CONCLUSIONS: The study results revealed
that serum cholesterol-related parameters are strictly associated with plasma
PCSK9 values, suggesting that PCSK9 function has a greater effect on serum total
cholesterol levels than SREBP-2 expression does. Furthermore, the total
cholesterol/HDL-C ratio was a better indicator for evaluating PCSK9 level than
total cholesterol.
PMID- 28691420
TI - Recent advances in tissue conditioners for prosthetic treatment: A review.
AB - Tissue conditioners (TCs) are short-term soft liners, formed in situ from a
mixture of a polymer powder and a liquid plasticizer. This article reviews the
recent advances in the composition, functions, clinical use, gelation process,
and physical properties of TCs and their effects on denture bases and oral
mucosa. TCs are used to improve the fit and function of an ill-fitting denture.
They can also be used to treat abused mucosal tissues underlying ill-fitting
acrylic dentures as temporary expedients. TCs are recommended as provisional
liners to maintain the fit of removable dentures and to prevent mechanical
irritation from the denture. TCs may also be used to rehabilitate cancer
patients. The polymer powder, used in the formulation of TCs generally consists
of polyethyl methacrylate (PEMA) and the liquid plasticizer is ester-based in
ethyl alcohol solution without an acrylic monomer. The plasticizers are low
molecular weight aromatic esters. Mixing of the powder and liquid results in
polymer chain entanglement and the formation of a coherent gel characterized by
viscoelastic behavior appropriate to its intended clinical use. The loss of
surface integrity and surface roughness of TCs are regarded as the main problems
in the denture bearing oral mucosa conditions resulting in inflammation of oral
mucosa of the denture-bearing area - denture stomatitis. TCs provide an even
distribution of masticatory force, accurately modeling itself to the changes
which occur during the healing of lesion of substrate and can act therapeutically
by incorporating antifungal or antibacterial agents.
PMID- 28691421
TI - Effects of long- and short-term darbepoetin-alpha treatment on oxidative stress,
inflammation and endothelial injury in ApoE knockout mice.
AB - BACKGROUND: Atherosclerosis and atherosclerosis-related complications are the
main cause of death in the world. Vascular injury in response to inflammation and
enhanced oxidant stress promotes endothelial dysfunction and leads to
atherosclerotic lesions. OBJECTIVES: Low-dose treatment with darbepoetin-alpha
may be a potential therapeutic tool for endothelial injury and atherosclerosis.
MATERIAL AND METHODS: In order to study the effect of darbepoetin-alpha on
endothelial injury and atherosclerosis, we used ApoE-/- mice as the
atherosclerotic mice model. We monitored atherosclerosis and plaque formation
histochemically in ApoE knockout mice at early and late stages of
atherosclerosis. Darbepoetin-alpha was injected intraperitoneally at a dose of
0.1 MUg/kg to ApoE-/- mice. The results of 2 ApoE-/- mice groups injected with
darbepoetin-alpha (early and late stages of atherosclerosis) were compared to the
results of the corresponding saline injected ApoE-/- mice groups and the control
(C57BL/6) mice. RESULTS: Lipid profile (total cholesterol, triglyceride),
inflammation (CRP, IL-6, histamine), endothelial injury (ICAM-1, selectin) and
oxidative stress markers (lipid peroxidation, protein oxidation) were
significantly increased in 4 atherosclerotic groups compared to the control
group. Short-term darbepoetin-alpha had no marked effects on indicators of
inflammation and endothelial injury in the ApoE knockout mice groups compared to
the ApoE knockout mice not treated with darbepoetin-alpha, however, darbepoetin
alpha significantly decreased 8-isoprostane and protein carbonyl content. Long
term darbepoetin-alpha treatment reduced oxidative stress in ApoE-/- mice.
CONCLUSIONS: This study contributes to understanding and elucidating the
biochemical changes occurring during early and late stages of atherosclerosis
development regarding lipid profile, inflammation, endothelial injury and
oxidative stress markers.
PMID- 28691422
TI - Hepatitis E virus antibodies in HIV-infected patients and blood donors from
western Poland: A preliminary report.
AB - BACKGROUND: Hepatitis E virus (HEV) infection is an emerging problem in
industrialized countries, including Europe. Little data exists on HEV
seroprevalence in Poland. OBJECTIVES: The aim of this study was to assess the
prevalence of anti-HEV IgG antibodies in Polish patients infected with the human
immunodeficiency virus (HIV) and blood donors. MATERIAL AND METHODS: Two hundred
and ten individuals (n = 105 of HIV-infected patients and n = 105 of ageand sex
matched blood donors from the same area; 178 men and 32 women), aged 18-50
(median age: 38 years), were tested for the presence of anti-HEV IgG antibodies
with the EUROIMMUN Anti-Hepatitis E Virus (HEV) ELISA (IgG) tests (Lubeck,
Germany). Additionally, some simple clinical and laboratory data was collected.
RESULTS: The overall anti-HEV IgG prevalence was 2.4% (5/210). One HIV-positive
patient (0.95%) and 4 blood donors (3.8%) were seropositive (p = 0.1745). All the
HEV-exposed individuals were men with a history of travel abroad and no icteric
disease in the past. CONCLUSIONS: Exposure to HEV infection among Polish HIV
patients and blood donors seems to be uncommon. Data on this issue is scarce and
conflicting for HIV-infected individuals. Further investigations applying
different serological tests and concomitant HEV RNA testing are needed to
reliably assess the risk and practical impact of HEV infection in Poland.
PMID- 28691423
TI - The magnitude of weight loss induced by metformin is independently associated
with BMI at baseline in newly diagnosed type 2 diabetes: Post-hoc analysis from
data of a phase IV open-labeled trial.
AB - BACKGROUND: The impact of metformin on body weight is variable in T2DM patients
among studies. The reasons for the discrepancies are still unknown. OBJECTIVES:
We aimed to find out the possible predictive factors of weight change induced by
metformin based on an analysis of a phase IV open-labeled trial. MATERIAL AND
METHODS: We performed a sub-analysis from a prospective, multi-center phase IV
open-labeled study in which 371 Chinese newly-diagnosed type 2 diabetes patients
received 16 weeks' extended-release metformin monotherapy. The clinical
characteristics including weight and laboratory assessments of subjects were
collected every 4 weeks. The weight changes from baseline to week 4, 8, 12 and 16
were calculated respectively. The patients were divided into 4 groups by quartile
statistics method according to magnitudes of weight change. RESULTS: Of 371
enrolled patients, 324 patients had the weight records from baseline to week 16.
The weight decreased gradually with each visit (p < 0.001) and the average weight
loss was 2 kg after 16 weeks' treatment of metformin. The patients with higher
BMI and bigger waist circumference at baseline showed a more pronounced weight
loss. However, the magnitudes of weight loss were independently associated with
BMI at baseline only. CONCLUSIONS: Metformin can lead to weight loss gradually in
newly-diagnosed type 2 diabetes patients. The magnitude of weight loss was
independently and only associated with baseline BMI.
PMID- 28691424
TI - An animal model of the procognitive properties of cysteine protease inhibitor and
immunomodulatory peptides based on colostrum.
AB - BACKGROUND: The positive effect of human cystatin C on the development of
Alzheimer's disease has been reported, as it inhibits the formation of beta
amyloid oligomers and amyloidogenesis. Cystatin C has been found to have a
neuroprotective effect by inhibiting cysteine proteases, inducing autophagy and
neurogenesis. There is a growing interest in the procognitive properties of
colostrum-based specimens, which could delay dementia and ameliorate memory
deterioration. OBJECTIVES: The aim of the study was to evaluate the influence of
ovocystatin and a Coloco peptide complex on the cognitive functions in reference
to Colostrinin, using a model of young (4 month-old) and old (10-month-old)
Wistar rats. MATERIAL AND METHODS: In the present study, the effects of
ovocystatin [100 MUg/rat] and the Coloco peptide [4 MUg/rat]derived from
colostrum were assessed with respect to the reference specimen, Colostrinin [4
MUg/rat]. The specimens were administered intraperitoneally and orally for 12
days. Cognitive functions were assessed using the Morris water maze (MWM).
RESULTS: The group of young rats that received ovocystatin orally obtained
significantly better results in the MWM compared to the placebo group (p < 0.05).
Similarly, the group of young rats receiving Coloco orally obtained better
results in the MWM compared to the placebo group and to the group of rats
receiving Colostrinin (p < 0.05). There were no statistically significant
differences in the oral and intraperitoneal administration of ovocystatin, Coloco
and Colostrinin in the group of old rats. CONCLUSIONS: The obtained results
suggest that oral administration of ovocystatin and Coloco has beneficial effects
on the cognitive functions of young rats.
PMID- 28691425
TI - Tolerance of combined radiochemotherapy in cervical cancer patients.
AB - BACKGROUND: Radiochemotherapy in cervical cancer was implemented to clinical
practice based on 5 randomized clinical trials, published at the end of the 20th
century, which showed improvement in the total and symptomless survivals by about
10-18%. The increase of therapeutic index of such treatment can take place only
when the efficiency of the treatment outweighs the increase of its toxicity.
Thus, it is necessary to monitor treatment reaction during radiochemotherapy.
OBJECTIVES: The aim of this study was to assess the acute post-radiation reaction
during radiochemotherapy for cervical cancer and the to analyze the reasons of
the unplanned course of combined treatment. MATERIAL AND METHODS: A group of
consecutive 176 cervical cancer patients in the clinical stage from IB to IIIB
acc. to FIGO classification who underwent radiochemotherapy were taken under
prospective observation in Clinical Gynecologic Radiotherapy Ward of the Lower
Silesian Cancer Center in Wroclaw between April 2010 and September 2012. Early
post-radiation reaction was assessed in RTOG/EORTC scale once a week. RESULTS:
During the treatment early post-radiation reaction of upper part of alimentary
duct was observed in 74.4% of the patients, the reaction of lower part of
gastrointestinal tract in 51.2%, and in bladder 44.8%. The most frequent symptoms
of post-radiation reaction are: nausea (73.3% of the patients), diarrhea (51.2%)
and vomiting (20.9%). Leucopenia was observed in 97.1% of the patients,
granulocytopenia in 70.4%, anemia in 69.2%, and thrombocytopenia in 25.5%. The
planned dose of radiotherapy was administered completely in 90.1% of the
patients. A break in radiotherapy was necessary in 15.7% of the patients. In
total, 44.8% of the patients did not receive radiochemotherapy according to the
plan, because of the side effects of the treatment (most often leucopenia,
thrombocytopenia and gastrointestinal reaction). CONCLUSIONS: The presented data
shows that radiochemotherapy causes the intensification of acute side effects of
treatment and may cause unplanned course of treatment and prolongation of the
total treatment time.
PMID- 28691426
TI - Physical activity - related changes in ADMA and vWF levels in patients with type
2 diabetes: A preliminary study.
AB - BACKGROUND: The activity and the role of methylarginine in diabetic patients are
subject to continuous research. The mechanism through which diabetes or insulin
resistance increases asymmetric dimethylarginine (ADMA) serum levels is not fully
understood. Studies indicate increased ADMA serum levels in patients with
hypertension, hypercholesterolemia and hyperhomocysteinemia. OBJECTIVES: The aim
of the study was to assess the changes in ADMA levels and its derivatives related
to the current disease process, as well as the levels of selected prothrombotic
factors and their changes induced by physical activity. MATERIAL AND METHODS: The
study included 44 patients: group A (22 patients) - patients with diabetes with
no vascular complications with mean age of 55.83 +/- 7.37 years; and group B (22
patients) - healthy volunteers with the mean age of 51.16 +/- 6.39 years. The
authors' questionnaire was used to collect sociodemographic data in the study
group. Physical exercise (Nordic walking) was practiced once per day for 30 min,
5 times a week. The assessment of peripheral blood parameters was performed using
the ABX MICROS OT 16-parameter hematology analyzer. Additionally, chromatographic
assay of serum levels of L-arginine, ADMA and symmetric dimethylarginine (SDMA)
was performed. RESULTS: There were statistically significant differences in ADMA
levels in the respondents with type 2 diabetes vs healthy volunteers after
training (0.763 +/- 0.043 vs 0.532 +/- 0.046; p = 0.001). CONCLUSIONS: ADMA and
SDMA levels in diabetic patients significantly exceeded standard values.
PMID- 28691427
TI - Pancreatic duct stones: A report on 16 cases.
AB - BACKGROUND: Pancreatolithiasis occurs in less than 1% of the general population
and is mainly recognized in patients with chronic pancreatitis. Selection of the
appropriate treatment method depends on the location, size and number of stones.
OBJECTIVES: The aim of the study was to analyze data concerning patients with
pancreatic duct stones who were hospitalized at Wroclaw Medical University's
Department of Gastroenterology and Hepatology from 2010 to 2014. MATERIAL AND
METHODS: The study presents data on 16 patients with pancreatic duct stones, who
constituted 7% of all 228 patients with chronic pancreatitis hospitalized at the
Department in the study period. The clinical data were compared with findings
reported in the literature. RESULTS: Epigastric pain was the most common symptom
reported by patients with pancreatolithiasis. The sensitivity of imaging tests in
the diagnosis of pancreatic duct stones was as follows: abdominal ultrasonography
- 31%, endoscopic retrograde cholangiopancreatography (ERCP) - 67%, computed
tomography - 71%, endoscopic ultrasonography - 73%. In 6 patients ERCP and
sphincterotomy were performed along with stenting of the main pancreatic duct.
Three other subjects were qualified for surgical treatment. In 7 selected
patients conservative treatment and further observation were applied.
CONCLUSIONS: Endoscopic ultrasonography is characterized by high sensitivity in
the diagnosis of pancreatic duct stones. ERCP is the first-line treatment in the
case of a small number of stones with sizes below 5 mm located in the head or
body of the pancreas. In the case of stones with sizes >= 5 mm, extracorporeal
shock wave lithotripsy should be performed before endoscopic drainage during
ERCP. Stenosis of the main pancreatic duct is the key risk factor for the
recurrence of pancreatolithiasis.
PMID- 28691428
TI - Stat proteins as intracellular regulators of resistance to myocardial injury in
the context of cardiac remodeling and targeting for therapy.
AB - The roles of STAT (signal transducers and activators of transcription) proteins
are widely discussed in relation to other agents like IFN-gamma that are involved
in cardiovascular diseases. STAT3 protects cardiomyocytes during endotoxic shock
and ischemia and prolongs survival of these cells by activation of antiapoptotic
genes like Bcl-2 and c-Fos. Moreover, IL-6 dependent expression of STAT3 is
probably responsible for hypertrophy of cardiomyocytes. On the contrary, STAT1
mediates cell death by induction of caspase-1. STAT6 probably enhances cellular
damage in myocardial infraction, which is significantly reduced in mice with the
knockout STAT6 gene. Considering these facts, we attempted to review in this
paper the role of STAT proteins in myocardial remodeling, highlighting STAT3 as a
potent mediator of cardioprotection. Our review also aims to acquaint a broad
audience of internal medicine practitioners with the STAT3-related molecular
mechanisms that underlie the therapeutic properties of such widely administered
drugs as angiotensin II type 1 (AT1) receptor antagonists and HMG-CoA reductase
inhibitors, such as losartan and lovastatin.
PMID- 28691429
TI - The effect of bariatric procedures on selected laboratory parameters of patients
from rural areas in Poland.
AB - BACKGROUND: Rural areas in Poland are inhabited by over 15 million people, i.e.
39.5% of Polish population, including about 5 million rural residents in the
Podlaskie province. The incidence of obesity is associated with increased
prevalence of obesity-related conditions. Studies that have been conducted do not
confirm the efficacy of conservative treatment of obesity, but show that
bariatric procedures produce the best longterm results. OBJECTIVES: The aim of
the study was to present the effects of bariatric obesity treatments
(laparoscopic adjustable gastric banding [LAGB], sleeve gastrectomy [SG], Roux-en
Y gastric bypass [RYGB]) on body mass index (BMI), selected diabetes control
parameters, dyslipidemia, hepatic and renal enzymes, blood count and hypertension
control. MATERIAL AND METHODS: The study group comprised a total of 100
consecutive patients from rural areas qualified for bariatric procedures. Most of
the patients (69.07%) underwent SG; 11.34% underwent LAGB; and 19.59% underwent
RYGB. Comorbidities included hypertension (35%), type 2 diabetes (52%) and
hyperlipidemia (15%). Glucose, insulin, HbA1C, alanine and aspartate
aminotransferase, bilirubin, total and fraction cholesterol, creatinine, urea,
uric acid and CRP levels, as well as blood count and blood pressure values, were
assessed prior to surgery and during follow-up visits 3 and 6 months after the
procedures. BMI, percentage of excess weight loss (%EWL) and percentage of excess
body mass index loss (%EBMIL) were assessed. RESULTS: Consistent, significant
decreases in BMI were observed 3 months (39.31 +/- 4.70) and 6 months (35.74 +/-
4.52) after surgery. The largest BMI reduction at the 6-month follow up was
observed for SG (12.29%), and the smallest was observed for LAGB (9.02%).
CONCLUSIONS: Improvements in the general health status of the patients were
observed, as well as normalization of metabolic parameters (glucose, cholesterol,
triglycerides, hepatic enzymes).
PMID- 28691430
TI - The mechanical properties of human dentin for 3-D finite element modeling:
Numerical and analytical evaluation.
AB - BACKGROUND: The FEM is often used in investigations of dentin loading conditions;
however, its anisotropy is mostly neglected. OBJECTIVES: The purpose of the study
was to evaluate the anisotropy and the elastic properties of an equivalent
homogenous material model of human dentin as well as to compare isotropic and
anisotropic dentin FE-models. MATERIAL AND METHODS: Analytical and numerical
dentin homogenization according to Luciano and Barbero was performed and E
modulus (E), Poisson's ratios (v) G-modulus (G) were calculated. The E-modulus of
the dentin matrix was 28.0 GPa, Poisson's ratio (v) was 0.3; finite element
models of orthotropic and isotropic dentin were created, loaded and compared
using Ansys(r) 14.5 and CodeAster(r) 11.2 software. RESULTS: Anisotropy of the
dentin ranged from 6.9 to 35.2%. E-modulus and G-modulus were as follows: E1 =
22.0-26.0 GPa, E2/E3 = 15.7-23.0 GPa; G12/G13 = 6.96-9.35 GPa and G23 = 6.08-8.09
GPa (highest values in the superficial layer). In FEM analysis of the
displacement values were higher in the isotropic than in the orthotropic model,
reaching up to 16% by shear load, 37% by compression and 23% in the case of shear
with bending. Strain values were higher in the isotropic model, up to 35% for the
shear load, 31% for compression and 35% in the case of shear with bending. The
decrease in the volumetric fraction and diameter of tubules increased the G and E
values. CONCLUSIONS: Anisotropy of the dentin applied during FEM analysis
decreased the displacements and strain values. The numerical and analytical
homogenization of dentin showed similar results.
PMID- 28691431
TI - Low-dose computed tomography in assessment of pulmonary abnormalities in children
with febrile neutropenia suffering from malignant diseases.
AB - BACKGROUND: Management of febrile neutropenia in pediatric patients is
challenging. Chest X-ray and CT scan help to identify infective foci; however,
exposure to radiation is a risk factor for development of secondary cancer. For
this reason, attention is paid to reducing radiation exposure. OBJECTIVES: The
aim of the study was to define the role of LDCT examination in the early
detection of pulmonary lesions in children during oncology or autoimmune
treatment complicated by neutropenia-related fever. Additionally, we focused on
the possibility to optimize image quality in low-dose protocols. MATERIAL AND
METHODS: The study included 138 pediatric patients (mean age 8.08 years) with
fever of 38.2 degrees C or higher with an absolute neutrophil count of 10 mm with
or without surrounding GGO or cavitations was sensitive at 77% and specific at
65% for fungal infection insert after neutrophil count: < 500/pL who underwent
chest X-ray and LDCT in the maximal interval of 24 h. CT findings were compared
with initial and final diagnosis as well as with clinical information. RESULTS:
LDCT detected pulmonary abnormalities in 116 patients (84.06%) showing ground
glass opacities (GGO) (n = 79), nodules (n = 60) and air-space consolidations (n
= 58). Radiologists correctly diagnosed infective lesions in 94 out of 116
patients (81.03%). The presence of random or pleural-based nodules. Diagnosis of
pyogenic infection based on the presence of air-space consolidation, pleural
effusion, GGO or centrilobular nodules showed a sensitivity of 78% and
specificity of 67%, whereas patchy or diffuse GGO, interstitial thickening and/or
air-space consolidation showed a high sensitivity of 81% and specificity of 68%
for Pneumocystis jirovecii pneumonia. CONCLUSIONS: LDCT is an excellent modality
in the diagnostic algorithm in patients with febrile neutropenia. It allows early
detection and detailed characterization of pulmonary abnormalities. Using
contrast, unenhanced CT examinations can further reduce radiation dose and
diminish the number of complications without a negative influence on the
diagnostic process.
PMID- 28691432
TI - Effect of diode lasers with wavelength of 445 and 980 nm on a temperature rise
when uncovering implants for second stage surgery: An ex-vivo study in pigs.
AB - BACKGROUND: Many surgical procedures in soft tissue are performed using diode
lasers. Recently, a novel diode laser operating at 445 nm wavelength was
introduced in dentistry. OBJECTIVES: The aim of our study was to evaluate the
time of surgery and an increase in temperature of titanium implants during its
uncovering using 445 and 980 nm wavelengths. MATERIAL AND METHODS: The research
included 45 pig mandibles (n = 45). The specimens were randomly divided into 3
groups (n = 15) according to the laser irradiation mode and wavelength; G1 - 445
nm laser, power: 3 W, continuous wave (CW), distance: 2 mm, power density: 7460
W/cm2, fiber: 320 MUm, noncontact mode; G2 - 445 nm laser (power: 2 W, CW, power
density: 4970 W/cm2, fiber: 320 MUm, contact mode; G3 (control) - 980 nm laser,
power: 2.5 W, CW, power density: 15920 W/cm2, fiber: 200 MUm, contact mode. The
temperature was measured with a 2 K-type thermocouples (a P1 at collar and a P2
at mid height of the implant). RESULTS: The mean temperature rises measured by
the P1 thermocouple were 16.9 degrees C, 36.1 degrees C and 21.6 degrees C in the
G1, G2 and G3 group, respectively. Significant differences in temperature rise
were found between the G1 and G2 group (p = 0.0007) and the G2 and G3 group (p =
0.01). The mean temperature rises measured by the P2 thermocouple were 1.8
degrees C, 1.4 degrees C and 5.6 degrees C in the G1, G2 and G3 group,
respectively. Significant differences in temperature rise were found between the
G1 and the G2 or G3 group (p = 0.0001). The significant differences among the
study groups in average time necessary for uncovering the implants amounted to
69.7, 54.4 and 83.6 s, respectively (p < 0.05). CONCLUSIONS: The application of
the 445 nm diode laser in non-contact mode reduced the temperature rise of the
implants. The additional pulse intervals during laser irradiation with wavelength
of 445 nm when operating in contact mode are needed.
PMID- 28691433
TI - Taking a critical look at the UNAIDS global estimates on paediatric and
adolescent HIV survival and death.
PMID- 28691434
TI - Universal antiretroviral therapy for HIV-infected children: a review of the
benefits and risks to consider during implementation.
AB - BACKGROUND: The 2016 World Health Organization (WHO) consolidated guidelines on
the use of antiretroviral drugs for treating and preventing HIV infection,
recommended to start all HIV-infected children on antiretroviral therapy (ART).
Here, we explore the possible benefits and risks of implementing universal ART
for all HIV-infected children and adolescents and outline some of the key
considerations that led to the 2016 revision of WHO guidelines. METHODS: We
conducted a review of the published data from 2000 to 2016, to ascertain the
clinical and programmatic benefits, as well as the risks of implementing
universal ART for all children. RESULTS AND DISCUSSION: Universal ART for all
children has the potential to increase treatment coverage, which in 2015 was only
51% globally, as well as providing several biological benefits, by preventing:
premature death/loss to follow-up, progressive destruction of the immune system,
poor growth and pubertal delay, poor neuro-cognitive outcomes and future burden
to the health care system with complications of untreated HIV-infection. However,
the strategy could be associated with risks, notably development of HIV drug
resistance, antiretroviral drug toxicities and increased costs to an already
stretched health system. CONCLUSION: Overall, our findings suggest that the
benefits could outweigh the risks and support universal ART for all HIV-infected
children, but recognize that national programmes will need to put measures in
place to minimize the risks if they choose to implement the strategy.
PMID- 28691436
TI - Viral kinetics in untreated versus treated acute HIV infection in prospective
cohort studies in Thailand.
AB - INTRODUCTION: The extent of viral replication during acute HIV infection (AHI)
influences HIV disease progression. However, information comparing viral load
(VL) kinetics with and without antiretroviral therapy (ART) in AHI is limited.
The knowledge gained could inform preventive strategies aimed at reducing VL
during AHI and therapeutic strategies to alter the viral kinetics that may
enhance the likelihood of achieving HIV remission. METHODS: The analysis utilized
VL data captured during the first year of HIV infection from two studies in
Thailand: the RV217 study (untreated AHI, 30 participants and 412 visits) and the
RV254 study (treated AHI, 235 participants and 2803 visits). Fiebig stages were
I/II (HIV RNA+, HIV IgM-) and Fiebig III/IV (HIV IgM+, Western blot
/indeterminate). Data were modelled utilizing spline effects within a linear
mixed model, with a random intercept and slope to allow for between-subject
variability and adjustment for the differences in variability between studies.
The number of knots in the quadratic spline basis functions was determined by
comparing models with differing numbers of knots via the Akaike Information
Criterion. Models were fit using PROC GLIMMIX in SAS v9.3. RESULTS: At enrolment,
there were 24 Fiebig I/II and 6 Fiebig III/IV individuals in the untreated group
and 137 Fiebig I/II and 98 Fiebig III/IV individuals in the treated group.
Overall, the median age was 27.5 years old, most were male (89%), and CRF01_AE
was the most common HIV clade (76%). By day 12 (4 days after ART in RV254), the
untreated group had a 2.7-fold higher predicted mean VL level compared to those
treated (predicted log VL 6.19 for RV217 and 5.76 for RV254, p = 0.05). These
differences increased to 135-fold by day 30 (predicted log VL 4.89 for RV217 and
2.76 for RV254) and 1148-fold by day 120 (predicted log VL 4.68 for RV217 and
1.63 for RV254) (p < 0.0001 for both) until both curves were similarly flat at
about day 150 (p = 0.17 between days 150 and 160). The VL trajectories were
significantly different between Fiebig I/II and Fiebig III/IV participants when
comparing the two groups and within the treated group (p < 0.001 for both).
CONCLUSIONS: Initiating ART in AHI dramatically changed the trajectory of VL very
early in the course of infection that could have implications for reducing
transmission potential and enhancing responses to future HIV remission
strategies. There is an urgency of initiating ART when acute infection is
identified. New and inexpensive strategies to engage and test individuals at high
risk for HIV as well as immediate treatment access will be needed to improve the
treatment of acute infection globally. CLINICAL TRIAL NUMBER: NCT00796146 and
NCT00796263.
PMID- 28691435
TI - Clinical and public health implications of acute and early HIV detection and
treatment: a scoping review.
AB - INTRODUCTION: The unchanged global HIV incidence may be related to ignoring acute
HIV infection (AHI). This scoping review examines diagnostic, clinical, and
public health implications of identifying and treating persons with AHI. METHODS:
We searched PubMed, in addition to hand-review of key journals identifying
research pertaining to AHI detection and treatment. We focused on the relative
contribution of AHI to transmission and the diagnostic, clinical, and public
health implications. We prioritized research from low- and middle-income
countries (LMICs) published in the last fifteen years. RESULTS AND DISCUSSION:
Extensive AHI research and limited routine AHI detection and treatment have begun
in LMIC. Diagnostic challenges include ease-of-use, suitability for application
and distribution in LMIC, and throughput for high-volume testing. Risk score
algorithms have been used in LMIC to screen for AHI among individuals with
behavioural and clinical characteristics more often associated with AHI. However,
algorithms have not been implemented outside research settings. From a clinical
perspective, there are substantial immunological and virological benefits to
identifying and treating persons with AHI - evading the irreversible damage to
host immune systems and seeding of viral reservoirs that occurs during untreated
acute infection. The therapeutic benefits require rapid initiation of
antiretrovirals, a logistical challenge in the absence of point-of-care testing.
From a public health perspective, AHI diagnosis and treatment is critical to:
decrease transmission via viral load reduction and behavioural interventions;
improve pre-exposure prophylaxis outcomes by avoiding treatment initiation for
HIV-seronegative persons with AHI; and, enhance partner services via notification
for persons recently exposed or likely transmitting. CONCLUSIONS: There are
undeniable clinical and public health benefits to AHI detection and treatment,
but also substantial diagnostic and logistical barriers to implementation and
scale-up. Effective early ART initiation may be critical for HIV eradication
efforts, but widespread use in LMIC requires simple and accurate diagnostic
tools. Implementation research is critical to facilitate sustainable integration
of AHI detection and treatment into existing health systems and will be essential
for prospective evaluation of testing algorithms, point-of-care diagnostics, and
efficacious and effective first-line regimens.
PMID- 28691437
TI - HIV misdiagnosis in sub-Saharan Africa: performance of diagnostic algorithms at
six testing sites.
AB - INTRODUCTION: We evaluated the diagnostic accuracy of HIV testing algorithms at
six programmes in five sub-Saharan African countries. METHODS: In this
prospective multisite diagnostic evaluation study (Conakry, Guinea; Kitgum,
Uganda; Arua, Uganda; Homa Bay, Kenya; Doula, Cameroun and Baraka, Democratic
Republic of Congo), samples from clients (greater than equal to five years of
age) testing for HIV were collected and compared to a state-of-the-art algorithm
from the AIDS reference laboratory at the Institute of Tropical Medicine,
Belgium. The reference algorithm consisted of an enzyme-linked immuno-sorbent
assay, a line-immunoassay, a single antigen-enzyme immunoassay and a DNA
polymerase chain reaction test. RESULTS: Between August 2011 and January 2015,
over 14,000 clients were tested for HIV at 6 HIV counselling and testing sites.
Of those, 2786 (median age: 30; 38.1% males) were included in the study.
Sensitivity of the testing algorithms ranged from 89.5% in Arua to 100% in Douala
and Conakry, while specificity ranged from 98.3% in Doula to 100% in Conakry.
Overall, 24 (0.9%) clients, and as many as 8 per site (1.7%), were misdiagnosed,
with 16 false-positive and 8 false-negative results. Six false-negative specimens
were retested with the on-site algorithm on the same sample and were found to be
positive. Conversely, 13 false-positive specimens were retested: 8 remained false
positive with the on-site algorithm. CONCLUSIONS: The performance of algorithms
at several sites failed to meet expectations and thresholds set by the World
Health Organization, with unacceptably high rates of false results. Alongside the
careful selection of rapid diagnostic tests and the validation of algorithms,
strictly observing correct procedures can reduce the risk of false results. In
the meantime, to identify false-positive diagnoses at initial testing, patients
should be retested upon initiating antiretroviral therapy.
PMID- 28691438
TI - HIV viral load as an independent risk factor for tuberculosis in South Africa:
collaborative analysis of cohort studies.
AB - INTRODUCTION: Chronic immune activation due to ongoing HIV replication may lead
to impaired immune responses against opportunistic infections such as
tuberculosis (TB). We studied the role of HIV replication as a risk factor for
incident TB after starting antiretroviral therapy (ART). METHODS: We included all
HIV-positive adult patients (>=16 years) in care between 2000 and 2014 at three
ART programmes in South Africa. Patients with previous TB were excluded. Missing
CD4 cell counts and HIV-RNA viral loads at ART start (baseline) and during follow
up were imputed. We used parametric survival models to assess TB incidence
(pulmonary and extrapulmonary) by CD4 cell and HIV-RNA levels, and estimated the
rate ratios for TB by including age, sex, baseline viral loads, CD4 cell counts,
and WHO clinical stage in the model. We also used Poisson general additive
regression models with time-updated CD4 and HIV-RNA values, adjusting for age and
sex. RESULTS: We included 44,260 patients with a median follow-up time of 2.7
years (interquartile range [IQR] 1.0-5.0); 3,819 incident TB cases were recorded
(8.6%). At baseline, the median age was 34 years (IQR 28-41); 30,675 patients
(69.3%) were female. The median CD4 cell count was 156 cells/uL (IQR 79-229) and
the median HIV-RNA viral load 58,000 copies/mL (IQR 6,000-240,000). Overall TB
incidence was 26.2/1,000 person-years (95% confidence interval [CI] 25.3-27.0).
Compared to the lowest viral load category (0-999 copies/mL), the adjusted rate
ratio for TB was 1.41 (95% CI 1.15-1.75, p < 0.001) in the highest group (>10,000
copies/mL). Time-updated analyses for CD4/HIV-RNA confirmed the association of
viral load with the risk for TB. CONCLUSIONS: Our results indicate that ongoing
HIV replication is an important risk factor for TB, regardless of CD4 cell
counts, and underline the importance of early ART start and retention on ART.
PMID- 28691439
TI - Awareness and willingness to use HIV pre-exposure prophylaxis among men who have
sex with men in low- and middle-income countries: a systematic review and meta
analysis.
AB - INTRODUCTION: To facilitate provision of pre-exposure prophylaxis (PrEP) in low-
and middle-income countries (LMIC), a better understanding of potential demand
and user preferences is required. This review assessed awareness and willingness
to use oral PrEP among men who have sex with men (MSM) in LMIC. METHODS:
Electronic literature search of Cochrane library, Embase, PubMed, PsychINFO,
CINHAL, Web of Science, and Google Scholar was conducted between July and
September 2016. Reference lists of relevant studies were searched, and three
authors contacted for additional data. Non-peer reviewed publications were
excluded. Studies were screened for inclusion, and relevant data abstracted,
assessed for bias, and synthesized. RESULTS: In total, 2186 records were
identified, of which 23 studies involving 14,040 MSM from LMIC were included. The
proportion of MSM who were aware of PrEP was low at 29.7% (95% CI: 16.9-44.3).
However, the proportion willing to use PrEP was higher, at 64.4% (95% CI: 53.3
74.8). Proportions of MSM aware of PrEP was <50% in 11 studies and 50-70% in 3
studies, while willingness to use PrEP was <50% in 6 studies, 50-70% in 9
studies, and over 80% in 5 studies. Several factors affected willingness to use
PrEP. At the individual domain, poor knowledge of PrEP, doubts about its
effectiveness, fear of side effects, low perception of HIV risk, and the need to
adhere or take medicines frequently reduced willingness to use PrEP, while PrEP
education and motivation to maintain good health were facilitators of potential
use. Demographic factors (education, age, and migration) influenced both
awareness and willingness to use PrEP, but their effects were not consistent
across studies. At the social domain, anticipated stigma from peers, partners,
and family members related to sexual orientation, PrEP, or HIV status were
barriers to potential use of PrEP, while partner, peer, and family support were
facilitators of potential use. At the structural domain, concerns regarding
attitudes of healthcare providers, quality assurance, data protection, and cost
were determinants of potential use. CONCLUSIONS: This review found that despite
low levels of awareness of PrEP, MSM in LMIC are willing to use it if they are
supported appropriately to deal with a range of individual, social, and
structural barriers.
PMID- 28691440
TI - High risk of loss to follow-up among South African children on ART during
transfer, a retrospective cohort analysis with community tracing.
AB - INTRODUCTION: Decentralization of HIV care for children has been recommended to
improve paediatric outcomes by making antiretroviral treatment (ART) more
accessible. We documented outcomes of children transferred after initiating ART
at a large tertiary hospital in the Eastern Cape of South Africa. METHODS:
Electronic medical records for all children 0-15 years initiating ART at Dora
Nginza Hospital (DNH) in Port Elizabeth, South Africa January 2004 to September
2015 were examined. Records for children transferred to primary and community
clinics were searched at 16 health facilities to identify children with
successful (at least one recorded visit) and unsuccessful transfer (no visits).
We identified all children lost to follow-up (LTF) after ART initiation: those
LTF at DNH (no visit >6 months), children with unsuccessful transfer, and
children LTF after successful transfer (no visit >6 months). Community tracing
was conducted to locate caregivers of children LTF and electronic laboratory data
were searched to measure reengagement in care, including silent transfers.
RESULTS: 1,582 children initiated ART at median age of 4 years [interquartile
range (IQR): 1-8] and median CD4+ of 278 cells/mm3 [IQR: 119-526]. A total of 901
(57.0%) children were transferred, 644 (71.5%) to study facilities; 433 (67.2%)
children had successful transfer and 211 (32.8%) had unsuccessful transfer. In
total, 399 children were LTF: 105 (26.3%) from DNH, 211 (52.9%) through
unsuccessful transfer and 83 (20.8%) following successful transfer. Community
tracing was conducted for 120 (30.1%) of 399 children LTF and 66 (55.0%)
caregivers were located and interviewed. Four children had died. Among 62
children still alive, 8 (12.9%) were reported to not be in care or taking ART and
18 (29.0%) were also not taking ART. Overall, 65 (16.3%) of 399 children LTF had
a laboratory result within 18 months of their last visit indicating silent
transfer and 112 (28.1%) had lab results from 2015 to 2016 indicating current
care. CONCLUSION: We found that only two-thirds of children on ART transferred to
primary and community health clinics had successful transfer. These findings
suggest that transfer is a particularly vulnerable step in the paediatric HIV
care cascade.
PMID- 28691443
TI - [Dilemmas in Physician - Patient Relationships].
PMID- 28691441
TI - Acute HIV infection detection and immediate treatment estimated to reduce
transmission by 89% among men who have sex with men in Bangkok.
AB - INTRODUCTION: Antiretroviral treatment (ART) reduces HIV transmission. Despite
increased ART coverage, incidence remains high among men who have sex with men
(MSM) in many places. Acute HIV infection (AHI) is characterized by high viral
replication and increased infectiousness. We estimated the feasible reduction in
transmission by targeting MSM with AHI for early ART. METHODS: We recruited a
cohort of 88 MSM with AHI in Bangkok, Thailand, who initiated ART immediately. A
risk calculator based on viral load and reported behaviour, calibrated to Thai
epidemiological data, was applied to estimate the number of onwards
transmissions. This was compared with the expected number without early
interventions. RESULTS: Forty of the MSM were in 4th-generation AHI stages 1 and
2 (4thG stage 1, HIV nucleic acid testing (NAT)+/4thG immunoassay (IA)-/3rdG IA-;
4thG stage 2, NAT+/4thG IA+/3rdG IA-) while 48 tested positive on third
generation IA but had negative or indeterminate western blot (4thG stage 3). Mean
plasma HIV RNA was 5.62 log10 copies/ml. Any condomless sex in the four months
preceding the study was reported by 83.7%, but decreased to 21.2% by 24 weeks on
ART. After ART, 48/88 (54.6%) attained HIV RNA <50 copies/ml by week 8,
increasing to 78/87 (89.7%), and 64/66 (97%) at weeks 24 and 48, respectively.
The estimated number of onwards transmissions in the first year of infection
would have been 27.3 (95% credible interval: 21.7-35.3) with no intervention, 8.3
(6.4-11.2) with post-diagnosis behaviour change only, 5.9 (4.4-7.9) with viral
load reduction only and 3.1 (2.4-4.3) with both. The latter was associated with
an 88.7% (83.8-91.1%) reduction in transmission. CONCLUSIONS: Disproportionate
HIV transmission occurs during AHI. Diagnosis of AHI with early ART initiation
can substantially reduce onwards transmission.
PMID- 28691444
TI - Reply to Lowenthal
PMID- 28691442
TI - Acceptability of woman-delivered HIV self-testing to the male partner, and
additional interventions: a qualitative study of antenatal care participants in
Malawi.
AB - INTRODUCTION: In the era of ambitious HIV targets, novel HIV testing models are
required for hard-to-reach groups such as men, who remain underserved by existing
services. Pregnancy presents a unique opportunity for partners to test for HIV,
as many pregnant women will attend antenatal care (ANC). We describe the views of
pregnant women and their male partners on HIV self-test kits that are woman
delivered, alone or with an additional intervention. METHODS: A formative
qualitative study to inform the design of a multi-arm multi-stage cluster
randomized trial, comprised of six focus group discussions and 20 in-depth
interviews, was conducted. ANC attendees were purposively sampled on the day of
initial clinic visit, while men were recruited after obtaining their contact
information from their female partners. Data were analysed using content
analysis, and our interpretation is hypothetical as participants were not offered
self-test kits. RESULTS: Providing HIV self-test kits to pregnant women to
deliver to their male partners was highly acceptable to both women and men. Men
preferred this approach compared with standard facility-based testing, as self
testing fits into their lifestyles which were characterized by extreme day-to-day
economic pressures, including the need to raise money for food for their
household daily. Men and women emphasized the need for careful communication
before and after collection of the self-test kits in order to minimize the
potential for intimate partner violence although physical violence was perceived
as less likely to occur. Most men stated a preference to first self-test alone,
followed by testing as a couple. Regarding interventions for optimizing linkage
following self-testing, both men and women felt that a fixed financial incentive
of approximately USD$2 would increase linkage. However, there were concerns that
financial incentives of greater value may lead to multiple pregnancies and lack
of child spacing. In this low-income setting, a lottery incentive was considered
overly disappointing for those who receive nothing. Phone call reminders were
preferred to short messaging service. CONCLUSIONS: Woman-delivered HIV self
testing through ANC was acceptable to pregnant women and their male partners.
Feedback on additional linkage enablers will be used to alter pre-planned trial
arms.
PMID- 28691445
TI - A wake-up call?
PMID- 28691446
TI - Giant cell or temporal arteritis?
PMID- 28691447
TI - Reply to Jawad
PMID- 28691449
TI - Evaluation of the intraepithelial papillary capillary loops in benign and
malignant oral lesions by in vivo Virtual Chromoendoscopic Magnification: a
preliminary study.
AB - This preliminary study aims to establish the Virtual Chromoendoscopic
Magnification (VCM) feasibility to visualize and distinguish the Intraepithelial
Papillary Capillary Loops (IPCL) patterns of benign oral pathologies from
malignant ones. Thirty-one consecutive subjects affected by oral
lesions/pathologies underwent white light examination and VCM imaging by the
Narrow Band Imaging System (Olympus Medical Systems Corp., Tokyo, Japan). A class
system of four IPCL types corresponding to progressive vessel disarray was
adopted. IPCL type IV were considered criterion of ?malignancy?. A
histopathological exam completed the diagnosis: sensitivity, specificity,
positive predictive value (PPV), negative predictive value (NPV), and accuracy
were calculated. IPCL patterns of benign oral entities ranged from types I to
III. IPCL type IV was associated with malignancy in 4 out of 6 cases.
Sensitivity, specificity, PPV, and NPV were 100%, 93%, 67% and 100%,
respectively. This study preliminarily describes IPCL patterns of different oral
mucosal diseases and confirms the association between IPCL IV and oral cancer.
PMID- 28691448
TI - Evaluation of chemical-physical properties and cytocompatibility of TheraCal LC.
AB - TheraCal LC (TLC, Bisco Inc., Schaumburg, IL, USA) is a light-cured, resin
modified, calcium silicate-filled base/liner material designed for direct and
indirect pulp-capping. In this study the result of the evaluation in vitro of the
biocompatibility and chemical-physical properties of TLC are reported. TLC
specimens were prepared under aseptic conditions in strict compliance with the
manufacturer?s instructions and sterilized. Osteoblast-like cells (MG63) were
used. For different time points, solubility, water uptake, alkalinizing activity
and cytotoxicity were evaluated. In ddH20 and in DMEM+FBS, TLC showed a loss of
material increasing simultaneously with the absorption capacity. The increase of
water uptake of the material promoting the solubilization of mineral ions in
medium is a requisite for a bioactive material. The alkalinizing activity is
correlated to antimicrobial/bacteriostatic activity and to the ability to favor
the formation of apatite deposits. The pH values for water absorption after
immersion of the disks ranged between 8 and 9 at each times of evaluation.
Cytotoxicity was not observed in MG63 cells treated with TLC and after 5 days,
the cells were organized to form a confluent monolayer as demonstrated by
fluorescence microscopy observation. TLC showed biocompatibility on MG63 cells
allowing a physiologic cell growth and differentiation. The chemical-physical
properties and biocompatibility of TLC observed in vitro in the present study,
allows considering this cement as an innovative pulp-capping material for the
vital pulp therapy.
PMID- 28691450
TI - Ultrasound imaging of oral fibroma: a case report.
AB - Oral mucosa is constantly under the influence of various internal and external
stimuli, therefore it is interested by a range of developmental disorders,
irritation, inflammation, and neoplastic conditions. Traumatic fibroma is one of
these lesions. The aim of this work is to obtain an ultrasound characterization
of a lip fibroma with a high frequency probe (8-18 MHz) as feasibility and
experimental model of this non-invasive technique in the oral mucosa compared
with its histo-pathological section. Ultrasound characterization of a fibroma in
a 50-year-old patient in the right retro commissural area of mucosa was
performed. The ultrasound images were compared with its histological image.
Fibroma is a traumatic lesion clinically recognizable and with a complex and well
defined histopathology structure. Although further investigations are necessary
to determine the potential of ultrasonographic images as an aid in the diagnosis
of oral lesions, this case report might be a model for ultrasound imaging
compared with its histological section.
PMID- 28691451
TI - Survey results of currently used techniques and materials by dentists for
fabrication of complete removable dental prostheses.
AB - The present study was based on the screening of procedures and materials used by
dentists in constructing complete removable dental prostheses, considering their
professional background and years of experience. Questions arose regarding
differences and similarities within the local dental society, of which
approximately 75% were trained in Europeans countries with differences in
academic background, and compared to international dentistry. A questionnaire web
site was used in order to anonymously collect answers to the survey by general
practicing and specialist dentists. The survey contained 28 multiple choice
questions that were based on 5 parameters: years of experience, location of
dental studies, specialization, location and field of specialization. One hundred
one survey sheets were collected. The results show statistical significance (p
less than 0.05) for the following comparisons: practicing time had an impact on
practitioner-technician interaction, while the level of qualification had an
effect on articulator and face-bow usage. Location of dental studies,
specialization and residency had impact on final impression materials, teeth set
up as well as tooth shape and color selection. The differences found between
dentists? working techniques set the ground for future research that should focus
on rating the success of the different methods towards a goal of creating
recommendations for an ideal set of working techniques.
PMID- 28691452
TI - Bilateral symmetry of anterior maxillary incisors: evaluation of a community
based population.
AB - The final outcome of dental treatment needs to be not only clinically sufficient,
but also esthetically pleasing. Bilateral symmetry in the maxillary incisor teeth
is of significant importance in esthetic dentistry. In restorative dentistry,
symmetry refers to the appearance of balance around the dental midline. The
purpose of this study was to measure and compare the maxillary incisor teeth
dimensions from both sides of the dental midline, in order to asses if this
symmetry occurs naturally. From the student community population at Tel Aviv
University, 66 students between the ages of 20-35 (35 males, 31 females) were
enrolled and gave consent. The inclusion criteria for this study were: upper
maxillary incisors that have never undergone restorative or rehabilitative
treatment, and no history of orthodontic treatment. Standardized digital
photographs were taken, and the length and width of the maxillary central and
lateral incisors were measured and proportions were calculated. SPSS was used to
compare the measured differences between teeth on the left versus right of the
midline. Tooth proportions were not significantly different between the left and
right sides. Asymmetry was found only between the lengths of the maxillary
lateral incisors (p=0.009); the width for these teeth was symmetrical. A
significant statistical difference was not found on most parameters when
evaluating symmetry of the upper incisors. Therefore, when treating the
esthetically important anterior of the mouth, care must be taken to ensure
bilateral symmetry to mirror the natural symmetry found in most patients.
PMID- 28691453
TI - The effect of enriching denture adhesives with chlorhexidine diacetate on the
proliferation of Candida albicans: an in vitro analysis.
AB - Denture adhesives are widely used in dentistry. The growth of Candida albicans on
the denture base is common on both jaws, particularly in elderly patients. A
strong correlation has been found between the growth of Candida albicans and
dentures, potentially leading to denture stomatitis. Recent studies show that the
addition of chlorhexidine diacetate (CHDA) to denture adhesives can have a
protective effect against denture stomatitis. The aim of this research is to
examine the antifungal properties of three denture adhesives when CHDA is added.
We hypothesize that the addition of CHDA to denture adhesives will result in
antifungal activity against Candida albicans. Three denture adhesive materials
(Corega, Protefix and Kukident) were prepared with and without the addition of
CHDA in order to measure whether CHDA increased the resistance of the adhesives
to the growth of Candida albicans. Dynamic and static intercellular changes were
assessed through direct contact test (DCT) and confocal microscopy. The tested
materials were evaluated immediately after setting and at 14 days post-setting.
When combined with CHDA, all three denture adhesive materials decreased Candida
albicans growth compared to the control (p less than 0.0001). This inhibition of
growth was more prominent in the first 24 h. The confocal microscopy results
supported the DCT findings. The addition of CHDA to denture adhesive pastes
inhibits growth of Candida albicans, and may potentially reduce the incidence of
denture stomatitis. Further studies are warranted.
PMID- 28691454
TI - Temperature changes of one-piece implants during the setting of acrylic resin
temporary crown. The effect of implant diameter. An in vitro study.
AB - The purpose of this work is to evaluate changes in temperature of one-piece
titanium implant surface during the setting of acrylic resin temporary crowns and
to correlate thermal changes to implant diameter. Thirty-three one-piece implants
(ARRP, Alpha-Biotec) were divided into 3 groups according to diameter size (G1=3
mm, G2=3.3 mm, G3=3.6 mm). Implants were mounted on an acrylic glass apparatus.
Thermocouples were positioned at the most coronal thread. Lower incisor temporary
polycarbonate crowns were filled with 80 MUL of self-curing acrylic resin and
positioned immediately on the implant abutment. Thermal changes of the implant
surface were recorded continuously for 10 min. Data were statistically analyzed
using one-way analysis of variance. The mean initial temperature (C0) of groups
G1, G2 and G3 was similar (24.79+/-0.78oC, 25.26+/-0.63oC, 24.97+/-1.06oC,
respectively). The setting of the acrylic resin temporary crown resulted in a
significant increase in the implant surface temperature of all groups. The mean
thermal amplitude (DeltaC) for groups G1, G2 and G3 were 6.79+/-1.02oC, 6.61+/
0.94oC, 6.65+/-1.26oC, respectively. The mean time to maximum temperature (Tmax)
for groups G1, G2 and G3 were 337.38+/-42.91 sec, 324.69+/-41.46 sec and 317.98+/
37.91 sec respectively (P>0.05). Direct application of auto-polymerizing resin to
the titanium abutment of one-piece implants significantly increased the cervical
implant surface temperature. Implant diameter did not influence the temperature
changes.
PMID- 28691455
TI - ADULT syndrome: dental features of a very rare condition.
AB - The Acro-Dermato-Ungual-Lacrimal-Tooth syndrome (ADULT syndrome) is one of the
rarest ectodermal dysplasias and it is associated with several malformations
involving especially the limbs. The most clinical features are the presence of
ectrodactyly, syndactyly, hypermelanosis or multiple lentigines, onhycodysplasia,
abnormalities in the lacrimal duct, recurrent conjuntivitis, photophobia,
mammarian hypoplasia, hypotrichosis and frontal alopecia, hypohydrosis, cutaneous
photosensitivity, nasal bridge prominence, exfoliative dermatitis and xerosis.
The ectodermal dysfunction expresses itself with conoid teeth, enamel hypoplasia,
dentinal dysplasia and especially hypodontia, with following functional and
aesthetic defects. We report the case of an 11-year-old Caucasian girl affected
by ADULT syndrome.
PMID- 28691456
TI - Genetic correlation between rheumatoid arthritis and periodontal disease: the
role of sex and IL-10.
AB - The chronic stimulation of the immune system due to the presence of bacterial
antigens within periodontal tissues has been associated with several autoimmune
diseases, like diabetes mellitus, infective endocarditis or cardiovascular
atherosclerosis. The current study aims at evaluating the correlation between
Rheumatoid Arthritis (RA) and Periodontal Disease (PD) with special attention to
genetic polymorphisms in cytokine expression. A total number of 34 patients
affected by RA were recruited. Each of them underwent haematochemical analysis
and data were collected for Rheumatoid Factor (RF), Anti-Citrullinated Protein?s
Antibody (CCP) and HLA-BDR1. DAS-28 questionnaire for disease activity was
fulfilled by the rheumatologist, while a periodontal examination was carried out
by the dental clinician and crevicular fluid samples were collected to evaluate
the IL-6, IL-10 and VDR polymorphysms. A connection between CCP and IL-10
polymorphisms was found, with IL-10 expressing protecting tendency against
periodontal disease when CCP are found in the bloodstream (p=0.0017). Finally,
males mainly expressed IL-10 predisposing genes (p=0.046), while females showed a
greater tendency to express RF (p=0.014) and CCP (p=0.050). This paper
corroborates the idea of a correlation between sex, IL-10 polymorphisms and RA,
which should be studied in depth, since recent papers have shown that IL-10
injected into joints seems to decrease inflammation.
PMID- 28691457
TI - Human beta2-defensin in oral lichen planus expresses the degree of inflammation.
AB - Syndrome (BMS). Seventeen OLP patients, with a positive histopathologic diagnosis
of the disease, were recruited into this study in order to measure the relative
quantity of HBD-2 in their saliva and crevicular fluid. The values were compared
with those collected from a group of 9 patients affected by the Burning Mouth
Syndrome (BMS) and with a control group (CTRL) of 9 patients. There was no
statistically significant difference between the groups (p=0.523; p=0.897).
However, patients affected by OLP showed a dycotomic distribution of values:
while 10 of them showed similar values to those found out in the other two
groups, 7 patients expressed high levels of HBD-2 and 3500 pg/ml was the
threshold to distinguish the subgroups. During the dental visit the clinician
classified OLP patients into two groups according to the clinical presentation of
the disease: reticular and hyperplastic (white OLP), atrophic and erosive forms
(red OLP). There was a statistical significant correlation between the clinical
and numeric classification of the patients (p=0.004; p=0.001), and the expression
of HBD-2 was higher in the red OLP group than in the white OLP group (p=0.000;
p=0.000). In conclusion, this study shows that HBD-2 represents an index to
assess active inflammation and it is probably linked to the presence of the
typical band-like CD8+ infiltrate in Oral Lichen Planus.
PMID- 28691458
TI - A ?burning? therapy for burning mouth syndrome: preliminary results with the
administration of topical capsaicin.
AB - Burning mouth syndrome is defined as an intraoral burning sensation for which no
medical or dental cause can be found. Recently, researchers have demonstrated an
altered trophism of the small nerve fibres and alterations in the numbers of TRPV
1 vanilloid receptors. Capsaicin is a molecule that is contained in hot peppers
and is specifically detected by TRPV-1 vanilloid receptors that are distributed
in the oral mucosae. We aimed at verifying if topical capsaicin could prove to be
an effective treatment of Burning Mouth Syndrome. A group of 99 BMS patients were
recruited. We subdivided the BMS patients into two groups: the collaborative
patients, who expressed a predominantly neuropathic pattern of symptoms, and the
non-collaborative patients, who were characterised by stronger psychogenic
patterns of the syndrome. Both groups underwent topical therapy with capsaicin in
the form of a mouth rinse 3 times a day for a long period. After 1 year of
treatment, the final overall success rate was approximately 78%, but with a
significant difference in the success rates of the two groups of patients (87%
and 20% among the collaborative and non-collaborative patients, respectively;
p=0.000). The use of topical capsaicin can improve the oral discomfort of BMS
patients, especially during the first month of therapy, but it is more effective
for those patients in which the neuropathic component of the syndrome is
predominant. Our hypothesis is that chronic stimulation with capsaicin leads to
decreases in burning symptoms. This phenomenon is called desensitisation and is
accompanied by substantial improvements in oral symptoms.
PMID- 28691459
TI - Periodontal microbioma and rheumatoid arthritis: The role of Porhyromonas
gingivalis.
AB - Rheumatoid Arthritis is a disease, which can be described as an autoimmune
response after molecular mimicry caused by infective agents. The current study
aims at evaluating the correlation between Rhematoid Arthritis (RA) and
Periodontal Disease (PD), with special attention to the microbioma detected in
the gums. Thirty-four patients with RD were recruited into the current study.
Among rheumatic parameters, Rheumatoid Factor (RF), anti-citrullinated protein
antibody (CCP), HLA-BDR1 and DAS28 were collected. A dental clinician evaluated
the periodontal screening record (PSR). Afterwards, 1 paper cone was inserted for
30 seconds into the gingival sulcus then sent to the laboratory for evaluation.
Quantitative PCR of 16S rRNA genes was performed with the hydrolysis probes
method to identify and evaluate the amount Porphyromonas gingivalis, Tannerella
forsythensis, Treponema denticola, Fusobacterium nucleatum and Campylobacter
rectus. There were no statistical differences in the composition of oral
microbioma between PSR groups. There were no statistical significant differences
between bacterial loads and serum values. On the contrary, a positive correlation
was found between the presence of Porphyromonas gingivalis in periodontal pockets
on one side and RF and CCP on the other. Therefore, the presence of Porhyromonas
gingivalis in periodontal pockets is associated to RA inflammatory indices.
PMID- 28691460
TI - The ?elfin face?: craniofacial and dental aspects of the Williams-Beuren
syndrome.
AB - Williams Syndrome is a rare congenital disorder characterized by supravalvular
aortic stenosis, peripheral pulmonary artery stenosis, mental retard and
dysmorfic facial features. As regards the dental aspects of the syndrome, the
deletion of the elastin gene induced clinicians to suspect periodontal
alterations with a greater frequency of gingivo-periodontitis, but on the
contrary no association between the syndrome and periodontal diseases have been
found. Furthermore, patients show a higher frequency of teeth hypoplasia, an
abnormal tooth morphology during primary dentition (12.5%) and during permanent
dentition. We present a case report of a 12-year-old Caucasian boy affected by
Williams-Beuren Syndrome who visited our hospital for a dental and orthodontic
evaluation.
PMID- 28691461
TI - Oral manifestations of selective IgA-deficiency: review and case-report.
AB - Immunoglobulin A deficiency is the most common primary immunodeficiency defined
as decreased serum level of IgA (less than 7 mg/dl) in the presence of normal
levels of other immunoglobulin isotypes. Most individuals with IgA deficiency are
asymptomatic and identified coincidentally. However, some patients may present
with recurrent infections, allergic disorders and autoimmune manifestations, such
as diabetes mellitus, Graves disease and celiac disease. The international
literature has not produced any kind of review yet about intra-oral
manifestations of selective IgA-deficiency. L.S., a 7-year-old Caucasian girl,
was examined at our hospital. After she had undergone a professional dental
cleaning, a symmetric, bilateral ulcerative gingivitis developed nearby the upper
second primary molars. The gingival ulcers were persistent and did not disappear
in the following 3 weeks. In the meantime, the young patient reported the
presence of gastrointestinal symptoms. IgA serum level was 4.5 mg/dl, while the
other isotypes levels were in the common range. The diagnosis of selective IgA
deficiency was formulated and the girl underwent further examination for the
specific IgG autoantibodies in celiac disease, which were not present.
Consequently, a full prevention program was planned. This case report emphasizes
the role of the paediatric dentist in the early detection of systemic disorder,
such as the immunological diseases. The oral cavity often reveals to be the first
site of manifestation of important systemic diseases. Immunoglobulin A (IgA)
deficiency is the most common primary immunodeficiency and is defined as a
decrease in serum IgA levels in the presence of normal levels of other
immunoglobulin isotypes (1). Serum IgA deficiency was first described in children
with ataxia-telangiectasia (2) and has since been identified in other patients,
including normal patients. The prevalence of IgA deficiency ranges from 1:223 to
1:1000 in community studies and from 1:400 to 1:3000 in healthy blood donors (3).
PMID- 28691462
TI - Odontomas: review of the literature and case reports.
AB - Odontomas are one of the most common Odontogenic Tumors of the jaw. The exact
etiology of odontomas is unknown. Histologically they are composed of various
formations of dental tissue (enamel, dentin, cementum and sometimes pulp). In the
WHO classification, they are divided into complex odontoma and compound odontoma.
Clinically, odontomas are generally asymptomatic and only in rare cases cause
swelling, pain, suppuration or bony expansion. Radiologically, the tumor is
initially lucent, but with time, it develops small calcifications, which
eventually coalesce to form a radiodense lesion with a lucent rim. Surgical
resection is the treatment of choice and there is no recurrence. The aim of this
paper is to define the principal characteristics and the treatment of these
lesions, based on literature and personal experience.
PMID- 28691463
TI - Use of the orbital fat pad in eyelid reconstruction.
AB - Eyelid reconstruction, though challenging, can produce a functional, esthetically
pleasing lid. This should preferably be accomplished with a one-stage procedure,
using robust, well-vascularized tissues similar to those being replaced, with
minimal associated donor morbidity. According to the experience with Bichat
pedicled flap in oral reconstruction, the authors propose the use of pedicle
infraorbital fat pad for repair of conjunctival defect. Seven patients underwent
eyelid reconstruction of full-thickness oncological or post-traumatic defects. In
all cases, the reconstruction involved an orbital fat pad flap for the posterior
lamella in addition to local flaps for the anterior lamella. All of the flaps
survived. The transferred fat flap had a complete epithelization, histologically
documented. No tumor relapse occurred in oncological cases. The results have been
satisfactory both for clinical evaluation and for the patients. Reconstruction of
the palpebral inner lamella with the orbital fat pad is a simple and low
morbidity procedure that has good morphological and functional results.
PMID- 28691464
TI - Parry Romberg Syndrome and linear facial scleroderma: management in pediatric
population.
AB - Among all different types of cutaneous scleroderma, Parry Romberg syndrome and
linear scleroderma "en coup de sabre" typically involve the visage. Gradual
degeneration of the tissues, from the skin up to the bone, is the stigmata of the
diseases and the range of clinical manifestations is wide. They typically start
during childhood and slowly progress before stabilizing. Considering the gravity
of the associated deformity and its impact on facial function and appearance, we
strongly advocate a prompt intervention that however must be tailored on
paediatric patients. There is not a general consensus on hemifacial atrophy
treatment, but autologous fat grafting has been proved to be a suitable
technique, due to its low morbidity, repeatability and efficacy in correcting
volume defects and in improving skin texture. Following the same concept of
safeness and non-invasiveness we propose 3D stereophotogrammetric acquisitions as
a possible tool for the pre- and post-surgical follow up, indispensable to
evaluate the surgical results. We present our case series composed of 8
paediatric patients, aged between 11 and 17 years, who underwent several
lipofilling procedures, from 2012 to 2016. Starting from 2015, 3D
stereophotgrammetric data has been obtained.
PMID- 28691465
TI - Bilateral coronoid hyperplasia: a report of six cases.
AB - Bilateral coronoid process hyperplasia is a rare condition defined as an abnormal
elongation of the mandibular coronoid process, formed of histologically normal
bone. Coronoid process hyperplasia usually develops progressively, and the
clinical symptoms are often similar to those of temporomandibular joint disorders
(TMD). Therefore, it is often misdiagnosed as TMD initially. From 2013 to 2016,
six patients were referred to our maxillofacial surgery unit by their dentist, to
evaluate mouth opening with suspected TMJ disorder. Average age was 30 years No
hypertrophy of the masseter muscles was found and the patient had no history of
pain and/or dysfunction of the temporomandibular joint. Average maximal incisal
opening was 16.3 mm. (Rance 13-20 mm). At the end of surgery the average mouth
opening achieved was of 40.3 mm. After 6 months from surgery an average mouth
opening of 41 mm was obtained, with no recidivism in the coronoid process growth
or decrease in the mouth opening. The only successful treatment to restore the
mouth opening caused by coronoid process hyperplasia is surgical correction of
coronoid-malar interference by coronoidectomy or coronoidotomy. Commencement of
physiotherapy is recommended to begin between three days and one week after
surgery. We also recommend the use of the TeraBite(r), a simple manual
physiotherapy device.
PMID- 28691466
TI - Oral melanoma with osteocartilagineous differentiation: a case report and
literature review.
AB - Osteocartilagineous differentiation within malignant melanoma is a rare
occurrence with several implications for diagnosis. Most of the reported cases
have occurred in acral lentiginous malignant melanomas. In this paper, the
authors describe the clinical, morphological, immunohistochemical features and
surgical treatment of a case of primary oral mucosal melanoma with
osteocartilaginous differentiation and they review the existing literature. The
clinical history of a 67-year-old man affected of oral malignant melanoma was
described from the first presentation to the second recurrence. FISH analysis on
primary lesion and on relapses showed positive results both in epithelioid and in
osteocondroblastic areas. Because of the scarcity of literature in osteogenic
melanoma, histological identification may be problematic and prognostic factors
and therapeutic protocols are nor well established. Immunohistochemical and
molecular techniques can help to diagnosis this rare lesion.
PMID- 28691467
TI - Bidirectional flux of fluids and microbiota at implant-abutment connection of FMD
Storm implant system: an in vitro stud y using RT-PCR.
AB - The purpose of the present microbiological study was to evaluate bacterial
leakage at implant-abutment connection level of a new type of implant (Storm
implant (FMD, Falappa Medical Devices(r), Rome, Italy) using Real-Time Polymerase
Chain Reaction (RT-PCR). This implant presents a polygonal external
implantabutment connection with a geometry that provides a hex on which engage
complementary abutments. To identify the capability of the implant to protect the
internal space from the external environment, the passage of genetically modified
Escherichia coli across implant-abutment interface was evaluated. Four Storm
implants (FMD, Falappa Medical Devices(r), Rome, Italy) were immerged in a
bacterial culture for 24 h and bacteria amount was measured inside implant
abutment interface with Real-time PCR. Bacteria were detected inside all studied
implants, with a median percentage of 15% for P. gingivalis and 14% for T.
forsythia. Our results are similar to those reported in the English literature.
Additional studies are needed to explore the relationship in terms of microbiota
between the internal implant and implant-prosthetic connection. In addition, the
dynamics of internal colonization needs to be thoroughly documented in
longitudinal in vivo studies. As a result, microbial leakage along the implant
abutment interface was acceptable and considered the most probable explanation
for peri-implantitis.
PMID- 28691468
TI - Bacterial colonization of the implant-abutment interface of conical connection
with an internal octagon: an in vitro study using real-time PCR.
AB - Bacterial leakage at the implant-abutment connection of a two-piece implant
system is considered the main cause of peri-implantitis. Prevention of bacterial
leakage at the implant-abutment connection is mandatory for reducing inflammation
process around implant neck and achieving bone stability. Micro-cavities at
implant-abutment connection level can favour bacterial leakage, even in modern
two-piece implant systems. The conical connection with an internal octagon (CCIO)
is considered to be more stable mechanically and allows a more tight link between
implant and abutment. As P. gingivalis and T. forsythia penetration might have
clinical relevance, it was the purpose of this investigation to evaluate
molecular leakage of these two bacteria in a new two-implant system with an
internal conical implant-abutment connection with internal octagon (Shiner XT,
FMD Falappa Medical Devices S.p.A. Rome, Italy). To verify the ability of the
implant in protecting the internal space from the external environment, the
passage of genetically modified Escherichia c oli across implant-abutment
interface was evaluated. Four Shiner XT implants (FMD, Falappa Medical
Devices(r), Rome, Italy) were immerged in a bacterial culture for 24 h and
bacteria amount was measured inside implant-abutment interface with Real-time
PCR. Bacteria were detected inside all studied implants, with a median percentage
of 6% for P. gingivalis and 5% for T. forsythia. Other comparable studies about
the tightness of the tested implant system reported similar results. The gap size
at the implant-abutment connection of CCIOs was measured by other authors
discovering a gap size of 1-2MUm of the AstraTech system and of 4MUm for the
Ankylos system. Bacterial leakage along implant-abutment connection of
cylindrical and tapered implants, Shiner XT, (FMD Falappa Medical Devices S.p.A.
Rome, Italy) showed better results compared to other implants. Additional studies
are needed to explore the relationship in terms of microbiota of the CCIO. In
addition, the dynamics of internal colonization needs to be thoroughly documented
in longitudinal in vivo studies.
PMID- 28691469
TI - Nasal reconstruction: our experience.
AB - The nose is a critically important aesthetic and functional portion of the face.
We can explore nasal defects following trauma or tumor resections. Reconstructive
techniques based on primary closure, skin graft, local flap, regional flap and
microvascular free tissue transfer provides an algorithmic framework applicable
to any reconstructive problem. From 2010 to 2016, 33 patients were treated with
nasal reconstruction. Malignant tumor resection was the main cause of nasal
defect. The most common tumor resected was BCC (basal cell carcinoma) followed by
SCC (squamous cell carcinoma). Recurrence of malignant tumor were also treated.
As described in the literature, we used the most common reconstructive techniques
to handle post-resection defects. Most of the defects involved the dorsum and the
ala of the nose, only rarely had the skeleton been affected by the resection.
When the cartilage had been sacrificed, a graft from the septum or from the ear
flap was harvested. All patients resulted in optimal reconstruction. In any case,
a second surgery was needed. All the surgical procedures were performed in one
single stage except for the paramedian forehead flap that required a second stage
for division and inset of the flap. All donor sites did not show functional and
aesthetic damage. All patients resulted in a morpho-functional restoration of the
area affected by the resection with a high success rate. Following the algorithm
when restoring the anatomical subunit is the base purpose has determined
satisfactory results.
PMID- 28691470
TI - Replica-guided trauma surgery.
AB - The aim of this study is to present a new approach to the surgical treatment of
fractures of the middle third of the face, based on the use of resorbable
materials and stereolithographic models. From 2009 to 2014, we treated 10 cases
of orbitozygomatic trauma mostly as secondary surgery. For each case, an
anatomical replica had been produced simulating the expected result and was then
used to contour the resorbable plates on its surface, even before the beginning
of the surgical procedure itself. The plates and meshes already bended act as a
guide to bony reduction procedure. No complications occurred: all patients healed
well, without inflammatory reactions. The results obtained corresponded to the
expected results. This technique has been employed for primary or secondary
treatment of fracturesof the middle third facial, where it is not always easy to
understand the displacement of bony segments and where the use of resorbables
plates could be particularly beneficial, as they do not interfere with the
maxillofacial skeleton physiology and avoid the necessity to remove plates and
screws. Combined use of stereolithographic model and resorbable materials allow a
new surgical approach based on the realization of the surgical procedure on the
model, then transferred from the patient to the model, thanks to plates and
meshes. This technique helps to overcome many of the limits of the conventional
technique: the need of minimal surgical access, in order to minimize facial
scarring and the vasculo-nervous structures that cross the head and neck district
and the obligation to restore not only the morphology but also the biological
functions.
PMID- 28691471
TI - Salivary glucose as a metabolic control marker in patients with type 2 diabetes.
AB - A study was made of the correlation between the serum and salivary glucose levels
in healthy subjects and in patients with type 2 diabetes, in order to establish
the validity of salivary glucose determination in monitoring glycemia. Ninety
seven subjects were included in the study: 47 diabetic patients and 46 controls,
aged between 40- and 80-years-of-age. Venous blood and saliva samples were
collected in both groups under fasting conditions and after administering a test
meal (15% proteins, 55% carbohydrates and 30% lipids). The glucose levels were
measured using the glucose oxidase technique. The salivary glucose levels were
seen to be greater in the diabetic group vs the controls both under fasting
conditions (baseline) and after the meal (postprandial) (p=0.023 and p=0.008,
respectively). A significant positive correlation was found between the serum and
salivary glucose levels at baseline and under resting conditions, particularly in
the diabetic group (r=0.389, p=0.002). The coefficient of determination of the
simple linear regression model was R2=0.042, showing salivary glucose to be
related to the blood glucose levels. In conclusion, salivary glucose
concentration is correlated to serum glucose, particularly in type 2 diabetics.
PMID- 28691472
TI - Neuroinflammation, Alzheimer?s disease and periodontal disease: is there an
association between the two processes?
AB - Alzheimer?s disease (AD) is a very common cause of dementia in developed
countries and increases its prevalence progressively with age. AD
etiopathogenesis is not yet understood. However, it is recognized that
neuroinflammation plays a key role in its pathogenesis with the activation of
microglia and the secretion of proinflammatory cytokines triggering irreversible
neurodegenerative deterioration. This paper is a short review of the relationship
between AD and periodontal disease (PD). Both processes may have common causes:
both are inflammatory diseases and the prevalence and progression increases with
ageing. However, we must consider that AD begins to develop many years before its
clinical diagnosis. It is thought that in this prodromal period a connection
could be established between both processes, both sustained by low intensity
inflammation. There are several studies that relate both processes such as the
possible systemic exposure to certain periodontopathogenic bacteria or the
proinflammatory cytokines and other elements. It is argued that there are no
modifiable factors such as age, or genetic factors, but that there are other
factors that could be avoided, modified or controlled such as periodontal
peripheral inflammation.
PMID- 28691473
TI - Oral probiotics in the management of gingivitis in diabetic patients: a double
blinded randomized controlled study.
AB - Diabetic patients are more prone to develop infections such as periodontal
diseases. Bacteriotherapy with the concept of using good bacterial strains to
replace the pathogenic ones emerged as a fascinating field due to the increasing
incidence of antibiotic resistance. The aim of this study was to evaluate if a
particular combination of probiotics (Lactobacillus Reuteri DSM 17938 and
Lactobaciullus Reuteri ATCC PTA 5289) is useful in treating gingivitis in
diabetic patients. Eighty adult patients with diagnosis of controlled diabetes
type II and gingivitis were enrolled for this study and randomized in two groups.
Only oral hygiene instructions were given. Bacteriotherapy (Lactobacillus
Reuteri) was administered to test group. Outcome measures were presence of Plaque
(P.I.) and Bleeding on Probing (B.O.P.). Data were collected at baseline and
after 30 days. At 30 days, both groups showed a statistically significant
clinical indexes reduction from baseline. More reduction was present in the test
group for P.I. (14%+/-6) and for B.O.P. (18%+/-4) and was statistically
significant (p less than 0.05). Within the limitations of this study,
bacteriotherapy can be considered effective in reducing plaque and BOP in
patients with controlled diabetes type II and gingivitis.
PMID- 28691474
TI - Cone-morse implant connection system significantly reduces bacterial leakage
between implant and abutment: an in vitro study.
AB - Osseointegrated implants are very popular dental treatments today in the world.
In osseointegrated implants, the occlusal forces are transmitted from prosthesis
through an abutment to a dental implant. The abutment is connected to the implant
by mean of a screw. A screw is the most used mean for connecting an implant to an
abutment. Frequently the screws break and are lost. There is an alternative to
screw retained abutment systems: the cone-morse connection (CMC). The CMC, thanks
to the absence of the abutment screw, guarantees no micro-gaps, no micro
movements, and a reduction of bacterial leakage between implant and abutment. As
P. gingivalis and T. forsythia penetration might have clinical relevance, it was
the purpose of this investigation to evaluate molecular leakage of these two
bacteria in a new CMC implants systems (Leone Spa(r), Florence, Italy). To
identify the capability of the implant to protect the internal space from the
external environment, the passage of genetically modified Escherichia coli across
implant-abutment interface was evaluated. Four cone-morse Leone implants
(Leone(r) Spa, Florence, Italy) were immerged in a bacterial culture for 24 h and
bacteria amount was then measured inside implant-abutment interface with Real
time PCR. Bacteria were detected inside all studied implants, with a median
percentage of 3% for P. gingivalis and 4% for T. forsythia. Cone-morse connection
implant system has very low bacterial leakage percentage and is similar to one
piece implants.
PMID- 28691475
TI - Genetic effects of BIOPAD(r) on fibroblast primary culture.
AB - BIOPAD(r) is an ivory-white soft sponge, made exclusively of lyophilized type I
native heterologous collagen extracted from horse flexor tendon, gelatine free,
that keeps its native structure specific to the body's skin tissue. BIOPAD(r) is
an active dressing, playing an active role in all stages of wound healing
process, stimulating granulation tissue growth and enhancing regeneration
tissues. It ensures balance between absorption and humidity at wound surface,
gaseous exchange of soft tissues during healing process, barrier to prevent
bacterial infections and it is completely non-adherent. The use of BIOPAD(r) is
painless for the patient and does not require removal or change of dressing. In
this work, we evaluated the effect of BIOPAD(r) on fibroblasts behavior in term
of cell viability, survival and growth and collagen production. The expression
levels of some adhesion and traction-resistance related genes (ELN, DSP, FN1,
FBN1, ITGB1, ITGA1, ITGA5, ITGA2, COL1A1, COL3A1) were analyzed using real time
Reverse Transcription-Polymerase Chain Reaction (real time RT-PCR). All genes,
except for ELN, DSP, ITGB1 and ITGA1 are up-regulated after 48 h of treatment.
Altogether, our results point out the good potential of BIOPAD(r) as a
biocompatible and regenerative tool in medicine.
PMID- 28691476
TI - Genetic effects of Vicryl(r) on fibroblast primary culture.
AB - Vicryl(r) (polyglactin 910) is an absorbable, synthetic, usually braided suture,
indicated for soft tissue approximation and ligation. Vicryl(r) has a special
coating for minimizing friction, easing passage through tissue and easy knot tie
down. It is synthetic for minimal tissue reaction. Fibroblasts are the main cells
of connective tissue that synthesize extracellular matrix. In this work, we tried
to judge the action of Vicryl(r) on fibroblasts behaviour. We evaluated the
expression levels of some adhesion and traction-resistance related genes (ELN,
DSP, FN1, FBN1, ITGB1, ITGA1, ITGA5, ITGA2, COL1A1, COL3A1) by using real time
Reverse Transcription-Polymerase Chain Reaction (real time RT-PCR). All but 2
genes resulted up-regulated after 48 h of treatment. Our preliminary results
point out the potential of Vicryl(r) as a biocompatible and regenerative tool in
medicine.
PMID- 28691477
TI - Surface modification of titanium alloys for biomedical application: from macro to
nano scale.
AB - Bone is a complexly structured tissue and hierarchically organized from macro to
nano levels of dimensions. Biomaterial devices developed to replace and interact
with bone tissues have been designed from the macro to nano perspective to
provide suitable performance in acquiring primary and biological stability. Macro
level designed features provide mechanical interlock and primary stability to
implants inside the bone. Surface micro and nano structures influence cells
behavior to promote the secondary or biological stability, reaching successful
osseointegration.
PMID- 28691478
TI - Mondani intraoral welding: historical process and main practical applications.
AB - The intraoral welder was invented by Dr. Pierluigi Mondani during the early 70?s
to weld titanium needle implants to a titanium bar in patient?s mouth and to load
them immediately by means of resin prosthesis. The clinical use documented dates
back to 1972. Over the years, many practical applications have been added to the
initial one, which have expanded the use of this device. In this scientific work,
main applications are described. The aim of the work was to trace the historical
process of intra-oral welding according to Mondani and describe the main
practical applications. Intra-oral welding is a process introduced by dr. Pier
Luigi Mondani of Genova (Italy) which allows to firmly conjoin titanium implants
of any shape by means of a titanium bar or also directly between them in the
mouth during surgery. The immediate stabilization achieved by intraoral welding
increases implants success rate, allows immediate loading even in situations of
bone atrophy, saves implants that are running into failure, re-evaluates
fractured implants, allows to stabilize submerged implants postponing prosthesis
management, allows to achieve efficient rehabilitation protocols to deal with
difficult cases. The 40-years? experience with intra-oral welding described in
this article, confirms the ease of use and efficiency in providing immediate
stabilization of titanium implants of all types.
PMID- 28691479
TI - Effect of platelet reach plasma on fibroblast primary culture: gene expression
evaluation.
AB - To correct skin imperfections, aesthetic medicine today makes use of injectable
dermal fillers that allow filling skin by increasing the volume of soft tissue.
Currently, there are many fillers usable for their excellent biocompatibility and
low allergic reactions that ensure good results and good compliance. Among these,
the most widely used filler is Human Plasma, obtained by centrifugation from
patient blood and processed through cycles of centrifugation and heating, until
it becomes a gel. In this work, we evaluated the effect of the Plasma on
fibroblasts behavior in terms of cell viability, survival, growth and collagen
production. To this aim, the expression levels of some adhesion and traction
resistance related genes (COL11A1, ELN, GDF6, IGF1, DSP, ELANE, HAS1, HYAL1,
COL1A1 and COL3A1) were analyzed using real time Reverse Transcription-Polymerase
Chain Reaction (real time RT-PCR). All genes, except for COL1A1, COL3A1 and
COL11A1, were up-regulated after 24 h of treatment. Altogether, our results point
out the good potential of Plasma. In particular, we appreciated an up-regulation
in some of the most important genes involved in bio-revitalization, such as
elastin and hyaluronic acid.
PMID- 28691481
TI - Collegial thoughts from Australia
PMID- 28691480
TI - Computer-guided implant insertion in a patient with impacted maxillary canines:
case report.
AB - The use of minimally invasive surgical techniques undoubtedly represents a huge
advantage for both the clinician and the patient. This case report shows the
possibility of making an implant-prosthetic rehabilitation in an upper jaw in a
patient who presented dental elements 1.3 and 2.3 in bone inclusion. The use of
computer-guided surgery offers us the possibility to carry out this type of
implant rehabilitation without performing the extraction of the above-mentioned
dental elements combined with the bone regeneration of the extraction sockets.
Consequently, surgery invasiveness and post-surgery complications are reduced to
a minimum. Additionally, the predictability of the methodology is evaluated with
specific software that enables a comparison between what is virtually planned and
what occurs in clinical practice.
PMID- 28691482
TI - Sensitive Electrochemical Detection of Nitric Oxide Release from Cardiac and
Cancer Cells via a Hierarchical Nanoporous Gold Microelectrode.
AB - The importance of nitric oxide (NO) in many biological processes has garnered
increasing research interest in the design and development of efficient
technologies for the sensitive detection of NO. Here we report on a novel gold
microelectrode with a unique three-dimensional (3D) hierarchical nanoporous
structure for the electrochemical sensing of NO, which was fabricated via a
facile electrochemical alloying/dealloying method. Following the treatment, the
electrochemically active surface area (ECSA) of the gold microelectrode was
significantly increased by 22.9 times. The hierarchical nanoporous gold (HNG)
microelectrode exhibited excellent performance for the detection of NO with high
stability. On the basis of differential pulse voltammetry (DPV) and amperometric
techniques, the obtained sensitivities were 21.8 and 14.4 MUA MUM-1 cm-2, with
detection limits of 18.1 +/- 1.22 and 1.38 +/- 0.139 nM, respectively. The
optimized HNG microelectrode was further utilized to monitor the release of NO
from different cells, realizing a significant differential amount of NO generated
from the normal and stressed rat cardiac cells as well as from the untreated and
treated breast cancer cells. The HNG microelectrode developed in the present
study may provide an effective platform in monitoring NO in biological processes
and would have a great potential in the medical diagnostics.
PMID- 28691483
TI - Using Femtosecond Laser Irradiation to Enhance the Vertical Electrical Properties
and Tailor the Morphology of a Conducting Polymer Blend Film.
AB - We report femtosecond infrared laser-induced selective tailoring of carrier
transport as well as surface morphology on a conducting polymer blend thin film.
Maximal 2.4 times enhancement on vertical current transport in poly(3
hexylthiophene):phenyl-C61-butyric acid methyl ester, was achieved by this
irradiation. The laser irradiation induced a photo expansion without
deteriorating its molecular structure and the film morphology could be customized
in the micron scale by adjusting the laser writing parameters. In the
photoexpanded region, the face-on populations were about 2.2 times larger in
comparison with the pristine region, which was a major contributor to the
enhanced carrier transport.
PMID- 28691484
TI - Nitric Oxide Nanosensors for Predicting the Development of Osteoarthritis in Rat
Model.
AB - Osteoarthritis (OA) is a chronic arthritic disease that causes the overproduction
of inflammatory factors such as nitric oxide (NO). This study develops a NO
nanosensor to predict the OA development. The nanosensor is synthesized by
encapsulating the NO sensing molecules (i.e., 4-amino-5-methylamino-2',7'
difluorofluorescein Diaminofluorescein-FM (DAF-FM)) within the biodegradable
poly(lactic-co-glycolic acid) nanoparticles. In vitro, the nanosensor allows the
monitoring of the NO release in interleukin-1beta-stimulated chondrocytes and the
alleviated effect of NG-monomethyl-l-arginine (a NO inhibitor) and
andrographolide (an anti-inflammatory agent). In the rat OA model, it permits the
quantification of NO level in joint fluid. The proposed NO nanosensor may
facilitate a noninvasive and real-time evaluation of the OA development.
PMID- 28691485
TI - Single-Drop Raman Imaging Exposes the Trace Contaminants in Milk.
AB - Better milk safety control can offer important means to promote public health.
However, few technologies can detect different types of contaminants in milk
simultaneously. In this regard, the present work proposes a single-drop Raman
imaging (SDRI) strategy for semiquantitation of multiple hazardous factors in
milk solutions. By developing SDRI strategy that incorporates the coffee-ring
effect (a natural phenomenon often presents in a condensed circle pattern after a
drop evaporated) for sample pretreatment and discrete wavelet transform for
spectra processing, the method serves well to expose typical hazardous molecular
species in milk products, such as melamine, sodium thiocyanate and lincomycin
hydrochloride, with little sample preparation. The detection sensitivity for
melamine, sodium thiocyanate, and lincomycin hydrochloride are 0.1 mg kg-1, 1 mg
kg-1, and 0.1 mg kg-1, respectively. Theoretically, we establish that the SDRI
represents a novel and environment-friendly method that screens the milk safety
efficiently, which could be well extended to inspection of other food safety.
PMID- 28691486
TI - Effects of Nonhydrostatic Stress on Structural and Optoelectronic Properties of
Methylammonium Lead Bromide Perovskite.
AB - We report synchrotron X-ray diffraction, photoconductivity, and photoluminescence
investigations of methylammonium-lead-bromide (MAPbBr3) under various stress
conditions, supported by density-functional-theory (DFT) calculations. The
properties of MAPbBr3 show substantial dependence on the hydrostatic conditions.
While nonhydrostatic compression of MAPbBr3 leads to amorphization above 2.4 GPa,
under quasi-hydrostatic (Ar) and hydrostatic (He) pressure, the sample remains in
crystalline phases. A sequence of phase transitions between two cubic phases and
orthorhombic Pnma phase is observed when using Ar, or no pressure-transmitting
medium (PTM). In helium-PTM only transitions between the two cubic structures and
a new isostructural phase transition with a large volume collapse to a third
cubic-phase at 2.7 GPa was observed. The photoluminescence measurements indicate
a pressure-induced band gap-narrowing in the cubic phase I, and a blue-shift in
the orthorhombic structure. DFT calculations illustrate that the dynamics of the
organic molecules and the inorganic lattice, coupled via the N-H...Br hydrogen
bonding interactions, affect the Pb-Br distance and the bandgap evolution under
pressure.
PMID- 28691487
TI - Low-Temperature Ohmic Contact to Monolayer MoS2 by van der Waals Bonded Co/h-BN
Electrodes.
AB - Monolayer MoS2, among many other transition metal dichalcogenides, holds great
promise for future applications in nanoelectronics and optoelectronics due to its
ultrathin nature, flexibility, sizable band gap, and unique spin-valley coupled
physics. However, careful study of these properties at low temperature has been
hindered by an inability to achieve low-temperature Ohmic contacts to monolayer
MoS2, particularly at low carrier densities. In this work, we report a new
contact scheme that utilizes cobalt (Co) with a monolayer of hexagonal boron
nitride (h-BN) that has the following two functions: modifies the work function
of Co and acts as a tunneling barrier. We measure a flat-band Schottky barrier of
16 meV, which makes thin tunnel barriers upon doping the channels, and thus
achieve low-T contact resistance of 3 kOmega.MUm at a carrier density of 5.3 *
1012/cm2. This further allows us to observe Shubnikov-de Haas oscillations in
monolayer MoS2 at much lower carrier densities compared to previous work.
PMID- 28691488
TI - Controllable Electrical Contact Resistance between Cu and Oriented-Bi2Te3 Film
via Interface Tuning.
AB - The contact resistance between metals and semiconductors has become critical for
the design of thin-film thermoelectric devices with their continuous
miniaturization. Herein, we report a novel interface tuning method to regulate
the contact resistance at the Bi2Te3-Cu interface, and three Bi2Te3 films with
different oriented microstructures are obtained. The lowest contact resistivity
(~10-7 Omega cm2) is observed between highly (00l) oriented Bi2Te3 and Cu film,
nearly an order of magnitude lower than other orientations. This significant
decrease of contact resistivity is attributed to the denser film connections,
lower lattice misfit, larger effective conducting contact area, and smaller width
of the surface depletion region. Meanwhile, our results show that the reduction
of contact resistance has little dependence on the interfacial diffusion based on
the little change in contact resistivity after the introduction of an effective
Ti barrier layer. Our work provides a new idea for the mitigation of contact
resistivity in thin-film thermoelectric devices and also gives certain guidance
for the size design of the next-level miniaturized devices.
PMID- 28691489
TI - Matsutakone and Matsutoic Acid, Two (Nor)steroids with Unusual Skeletons from the
Edible Mushroom Tricholoma matsutake.
AB - Matsutakone (1), a novel sterol with an unprecedented polycyclic ring system,
together with a new norsteroid matsutoic acid (2) were isolated from the fruiting
bodies of Tricholoma matsutake. Their structures and absolute configurations were
assigned by extensive spectroscopic analyses and computational methods. Bioassay
results showed that compounds 1 and 2 exhibited inhibitory activities against
acetylcholinesterase (IC50 20.9 MUM for 1).
PMID- 28691490
TI - Synthesis of (+/-)-Aphanorphine Using Rh-Catalyzed Cyclohydrocarbonylation.
AB - A facile formal synthesis to aphanorphine and its analogue is described,
featuring Rh-catalyzed cyclohydrocarbonylation of 2-aminodihydronaphthalene to
the bridged benzazepine core. Subsequent introduction of the methyl group and
functional group transformation complete the synthesis of aphanorphine and its
analogue over eight steps.
PMID- 28691491
TI - Peptidoglycan Cross-Linking Preferences of Staphylococcus aureus Penicillin
Binding Proteins Have Implications for Treating MRSA Infections.
AB - Methicillin-resistant Staphylococcus aureus (MRSA) infections are a global public
health problem. MRSA strains have acquired a non-native penicillin-binding
protein called PBP2a that cross-links peptidoglycan when the native S. aureus
PBPs are inhibited by beta-lactams. It has been proposed that the native S.
aureus PBPs can use cell wall precursors having different glycine branch lengths
(penta-, tri-, or monoglycine), while PBP2a can only cross-link peptidoglycan
strands bearing a complete pentaglycine branch. This hypothesis has never been
tested because the necessary substrates have not been available. Here, we
compared the ability of PBP2a and two native S. aureus transpeptidases to cross
link peptidoglycan strands bearing different glycine branches. We show that
purified PBP2a can cross-link glycan strands bearing penta- and triglycine, but
not monoglycine, and experiments in cells provide support for these findings.
Because PBP2a cannot cross-link peptidoglycan containing monoglycine, this study
implicates the enzyme (FemA) that extends the monoglycine branch to triglycine on
Lipid II as an ideal target for small molecules that restore sensitivity of MRSA
to beta-lactams.
PMID- 28691492
TI - Hypervalent Iodine-Mediated Oxidative Rearrangement of N-H Ketimines: An Umpolung
Approach to Amides.
AB - An umpolung approach to amides via hypervalent iodine-mediated oxidative
rearrangement of N-H ketimines under mild reaction conditions is described. This
strategy provides target amides with excellent selectivity in good yields. In
addition, preliminary mechanistic studies demonstrated that the migration
preference depends on both steric and electronic effects of the migrating groups.
PMID- 28691494
TI - Two New Tools for Glycopeptide Analysis Researchers: A Glycopeptide Decoy
Generator and a Large Data Set of Assigned CID Spectra of Glycopeptides.
AB - The glycopeptide analysis field is tightly constrained by a lack of effective
tools that translate mass spectrometry data into meaningful chemical information,
and perhaps the most challenging aspect of building effective glycopeptide
analysis software is designing an accurate scoring algorithm for MS/MS data. We
provide the glycoproteomics community with two tools to address this challenge.
The first tool, a curated set of 100 expert-assigned CID spectra of
glycopeptides, contains a diverse set of spectra from a variety of glycan types;
the second tool, Glycopeptide Decoy Generator, is a new software application that
generates glycopeptide decoys de novo. We developed these tools so that emerging
methods of assigning glycopeptides' CID spectra could be rigorously tested.
Software developers or those interested in developing skills in expert (manual)
analysis can use these tools to facilitate their work. We demonstrate the tools'
utility in assessing the quality of one particular glycopeptide software package,
GlycoPep Grader, which assigns glycopeptides to CID spectra. We first acquired
the set of 100 expert assigned CID spectra; then, we used the Decoy Generator
(described herein) to generate 20 decoys per target glycopeptide. The assigned
spectra and decoys were used to test the accuracy of GlycoPep Grader's scoring
algorithm; new strengths and weaknesses were identified in the algorithm using
this approach. Both newly developed tools are freely available. The software can
be downloaded at http://glycopro.chem.ku.edu/GPJ.jar.
PMID- 28691493
TI - Integrating Next-Generation Genomic Sequencing and Mass Spectrometry To Estimate
Allele-Specific Protein Abundance in Human Brain.
AB - Gene expression contributes to phenotypic traits and human disease. To date,
comparatively less is known about regulators of protein abundance, which is also
under genetic control and likely influences clinical phenotypes. However,
identifying and quantifying allele-specific protein abundance by bottom-up
proteomics is challenging since single nucleotide variants (SNVs) that alter
protein sequence are not considered in standard human protein databases. To
address this, we developed the GenPro software and used it to create personalized
protein databases (PPDs) to identify single amino acid variants (SAAVs) at the
protein level from whole exome sequencing. In silico assessment of PPDs generated
by GenPro revealed only a 1% increase in tryptic search space compared to a
direct translation of all human transcripts and an equivalent search space
compared to the UniProtKB reference database. To identify a large unbiased number
of SAAV peptides, we performed high-resolution mass spectrometry-based proteomics
for two human post-mortem brain samples and searched the collected MS/MS spectra
against their respective PPD. We found an average of ~117 000 unique peptides
mapping to ~9300 protein groups for each sample, and of these, 977 were unique
variant peptides. We found that over 400 reference and SAAV peptide pairs were,
on average, equally abundant in human brain by label-free ion intensity
measurements and confirmed the absolute levels of three reference and SAAV
peptide pairs using heavy labeled peptides standards coupled with parallel
reaction monitoring (PRM). Our results highlight the utility of integrating
genomic and proteomic sequencing data to identify sample-specific SAAV peptides
and support the hypothesis that most alleles are equally expressed in human
brain.
PMID- 28691495
TI - Synthesis of Hedgehoglike F-TiO2(B)/CNT Nanocomposites for Sonophotocatalytic and
Photocatalytic Degradation of Malachite Green (MG) under Visible Light: Kinetic
Study.
AB - The present study describes the preparation of hedgehoglike F-doped titanium
dioxide bronze (F-TiO2(B)) and its nanocomposites containing single-walled and
multiwalled carbon nanotubes (SWCNTs, MWCNTs) by using combined ball milling
hydrothermal processes. Then, sonophotocatalytic and photocatalytic degradation
of malachite green (MG) dye from aqueous solution using prepared materials was
performed. The results show that F-TiO2(B)/SWCNT displays a good
sonophotocatalytic and photocatalytic performance among other products under
visible light. In addition, they indicated that the efficiency of malachite green
degradation is more than 95% and 91% for sonophotocatalytic and photocatalytic
methods, respectively. Also, they demonstrate that the photocatalytic efficiency
of catalysts increases in the presence of ultrasound and the sonophotocatalysis
process followed a second-order kinetics. The catalysts have been characterized
by transmission electron microscopy (TEM), field emission scanning electron
microscopy (FESEM), X-ray diffraction analysis (XRD), Fourier transform infrared
spectroscopy (FTIR), UV-vis diffuse reflectance spectroscopy, and energy
dispersive X-ray spectroscopy (EDX). The analyzed data confirmed the presence of
CNTs and fluorine (F) as dopant in all nanocomposites. The presented hybrid
method reduced the band gap from 3.02 eV for F-TiO2(B) to 2.7 eV for F
TiO2(B)/SWCNT nanocomposite.
PMID- 28691496
TI - Single Cell Level Quantification of Nanoparticle-Cell Interactions Using Mass
Cytometry.
AB - Quantification of cell-associated nanoparticles (NPs) is a paramount question in
both nanomedicine and nanotoxicology. Inductively coupled plasma mass
spectrometry is a well-established method to resolve cell-associated (metal) NPs
in bulk cell populations, however, such analysis at single cell level remains a
challenge. Here we used mass cytometry, a technique that combines single cell
analysis and time-of-flight mass spectrometry, to quantitatively analyze extra-
and intracellular silver (Ag) in individual Ag NP exposed human T-lymphocytes.
The results revealed significant population heterogeneity: for example, in
lymphocytes exposed to 3 MUg of 30 nm branched polyethylene imine coated Ag
NPs/mL the extracellularly bound Ag varied from 79 to 560 fg and cellular uptake
from 17 to 121 fg. Similar amplitude of heterogeneity was observed in cells
exposed to various doses of Ag NPs with other sizes and surface coatings,
demonstrating the importance of single cell analysis when studying NP-cell
interactions. Although mass cytometry has some shortcomings such as inability to
analyze potential transformation or dissolution of NPs in cells, we consider this
method as the most promising for quantitative assessment of cell-NP interaction
at single cell level.
PMID- 28691497
TI - Increased mortality risk in diabetic patients discharged from hospital with
insulin therapy after an acute myocardial infarction: Data from the FAST-MI 2005
registry.
AB - BACKGROUND: Merits of insulin use for diabetes treatment in patients with
advanced atherosclerosis are debated. This observational study conducted in
diabetic patients after an acute myocardial infarction aimed to assess whether
insulin prescription at discharge (IPD) was related to all-cause mortality during
follow-up. METHODS: Subjects were diabetic patients admitted in intensive- or
coronary-care units for acute myocardial infarction (consecutively recruited in
223 centres in France) and discharged alive from the hospital, with or without an
IPD. Vital status after five years was obtained and the relationship between
insulin prescription at discharge and survival was studied. RESULTS: Overall,
1221 diabetic patients were discharged alive and 38% had an IPD. Factors
independently related to IPD were female gender, hospitalization in a public
hospital, duration of diabetes, HbA1c level, smoking, peripheral artery disease,
history of coronary heart disease and Killip class. After adjustment, IPD was
independently related to all-cause mortality after five years of follow-up
(adjusted hazard ratio = 1.72 (1.42-2.09), p<0.001). This increased mortality in
subjects with IPD was also observed in propensity matched analyses, when subjects
actually treated or actually not treated with insulin at discharge were compared
in two groups matched on their computed probability of having had insulin
prescribed. CONCLUSIONS: Insulin was preferably prescribed in seriously affected
patients, regarding diabetes and cardiovascular risk. However, insulin
prescription at discharge was associated with increased all-cause mortality after
extensive adjustments for confounders. These results suggest possible intrinsic
harmful effects of insulin in high-risk diabetic patients after myocardial
infarction.
PMID- 28691498
TI - Delivering End-of-Life Cancer Care: Perspectives of Providers.
AB - OBJECTIVES: Persistent gaps in end-of-life cancer care delivery and growing
associated expenditures remain imminent US public health issues. The objective of
this study was to understand clinical providers' experiences delivering cancer
care for patients at the end of life and their perspectives on potential
solutions to improve quality of care. METHODS: Semistructured interviews were
conducted with 75 cancer care providers across the United States. The interviews
were recorded, transcribed, and analyzed using constant comparative method of
qualitative analysis. RESULTS: Providers identified 3 major cancer care delivery
challenges including lack of time to educate patients and caregivers due to
clinical volume and administrative burdens, ambiguity in determining both
prognosis and timing of palliative care at the end-of-life, and lack of adequate
systems to support non-face-to-face communication with patients. To address these
challenges, providers endorsed several options for clinical practice redesign in
their settings. These include use of a lay health worker to assist in addressing
early advance care planning, proactive non-face-to-face communication with
patients specifically regarding symptom management, and community and in-home
delivery of cancer care services. DISCUSSION: Specific strategies for cancer care
redesign endorsed by health-care providers may be used to create interventions
that can more efficiently and effectively address gaps in end-of-life cancer
care.
PMID- 28691499
TI - Eradication of HIV from Tissue Reservoirs: Challenges for the Cure.
AB - The persistence of HIV infection, even after lengthy and successful combined
antiretroviral therapy (cART), has precluded an effective cure. The anatomical
locations and biological mechanisms through which the viral population is
maintained remain unknown. Much research has focused nearly exclusively on
circulating resting T cells as the predominant source of persistent HIV, a
strategy with limited success in developing an effective cure strategy. In this
study, we review research supporting the importance of anatomical tissues and
other immune cells for HIV maintenance and expansion, including the central
nervous system, lymph nodes, and macrophages. We present accumulated research
that clearly demonstrates the limitations of using blood-derived cells as a proxy
for tissue reservoirs and sanctuaries throughout the body. We cite recent studies
that have successfully used deep-sequencing strategies to uncover the complexity
of HIV infection and the ability of the virus to evolve despite undetectable
plasma viral loads. Finally, we suggest new strategies and highlight the
importance of tissue banks for future research.
PMID- 28691500
TI - Factors associated with sustained community employment among adults with autism
and co-occurring intellectual disability.
AB - Sustaining community employment is a challenge for adults with autism spectrum
disorders, especially for those who have co-occurring intellectual disability,
but factors contributing to this employment outcome have not been fully
evaluated. This study utilized longitudinal data to explore the impact of
contextual influences, family factors, and individual characteristics on
sustained employment over approximately 18 months ( N = 105). Very few adults
with autism spectrum disorder and intellectual disability achieved sustained
employment (14.3%). The results indicated that more independent daily living
skills, a higher family income, a larger maternal social network, an inclusive
school environment in early childhood, and currently living in an area with a
larger population size were associated with significantly greater odds of
sustaining employment. Follow-up analyses suggested that managing personal care
is particularly important for employment.
PMID- 28691501
TI - Factors Contributing to Hospital Stay and Total Inpatient Charges in Total Ankle
Arthroplasty: Review of the National Inpatient Sample.
AB - : Total ankle arthroplasty (TAA) is commonly performed for end-stage ankle
osteoarthritis. Given rising costs and declining reimbursements, identifying
variables increasing length of stay (LOS) and total inpatient charges (TICs) of
TAA is necessary for providing cost-effective care. The National Inpatient Sample
(NIS) database was reviewed between 1993 and 2010, identifying LOS and TIC for
TAA. Using a multivariate analysis, patient comorbidities, demographics, payment,
and hospital details were evaluated. Median LOS decreased from 5 to 2 days,
whereas median TICs increased from $21 382.53 to $62 028.00. Regionally, the
South and Midwest had decreased TICs, whereas the West had an increased TIC.
There was no significant difference in LOS geographically. Rural hospitals
demonstrated decreased TICs, whereas urban private hospitals showed decreased LOS
and decreased TICs. Large hospitals were associated with increased LOS and TICs.
Compared with Medicare, private insurers demonstrated decreased LOS with
equivalent TICs. Diabetics significantly increased mean LOS by 1 day, without a
significantly increased TIC. Despite a decreased LOS, hospital charges have
increased between 1993 and 2010 in TAA. We found that regional differences and
hospital characteristics were associated with differences in LOS and TICs.
Identification of these factors provides important information to facilities and
surgeons. LEVELS OF EVIDENCE: Level IV: Economic/decision analysis.
PMID- 28691502
TI - Associations of quality of life with health-related characteristics among
children with autism.
AB - We examine whether behavioral, mental health, and physical health characteristics
of children with autism are associated with baseline and change in health-related
quality of life. We measured health-related quality of life with the Pediatric
Quality of Life Inventory 4.0 total scores from children enrolled in the Autism
Treatment Network. We used linear mixed model regressions with random slopes.
Predictors of lower health-related quality of life at baseline included
demographic and insurance characteristics, diagnosis, higher Child Behavior
Checklist internalizing and externalizing scores, sleep problems by Children's
Sleep Habits Questionnaire, seizures, gastrointestinal problems, and mental
health problems. Several characteristics had different associations over time.
This study demonstrates that in addition to behavioral and autism-related
characteristics, physical and mental health conditions are associated with health
related quality of life in children with autism.
PMID- 28691503
TI - Improving Transitions of Care for Veterans Transferred to Tertiary VA Medical
Centers.
AB - Veterans are often transferred from "spoke" Veterans Administration (VA) clinics
or hospitals to "hub" tertiary VA hospitals for advanced inpatient care, but they
face significant barriers to safe transitions home. The Transitions Nurse Program
was developed as an intervention to address the unique needs of this population.
A difference-in-differences (DiD) analysis was used to compare outcomes between
303 veterans enrolled in this program and veterans transferred from the same
spoke sites to a second, similar tertiary VA hub. Veterans enrolled in the
program had significantly increased rates of follow-up with their primary care
clinic within 14 days of discharge (DiD estimate: 10.43%, 95% confidence interval
= 1.20 to 19.66), and a trend toward fewer unplanned 30-day readmissions (DiD
estimate: -6.9%, 95% confidence interval = -14.2 to 0.31%, P = .06). There were
no significant differences in 30-day emergency department visits or costs.
Lessons learned from this preliminary intervention can inform implementation at
other VA and non-VA sites.
PMID- 28691504
TI - Takotsubo Cardiomyopathy: Another Form of Cardiorenal Syndrome.
AB - Takotsubo cardiomyopathy (TC) is a life-threatening syndrome with ambiguous
pathophysiology. The interdependency between heart failure and kidney failure
(KF) is well established, but the influence of KF on TC outcome is not known.
This single-center cohort from January 2003 to September 2015 consisted of 114
consecutive patients with TC. They were divided into 2 groups according to the
presence (n = 32, 29.6%) or absence (n = 76, 70.3%) of KF. The end point of this
retrospective study was a composite of in-hospital events, all-cause mortality,
rehospitalization due to heart failure, stroke, and recurrence of TC (mean follow
up: 5 years). Although there were no differences in baseline characteristics
between patients with/without KF, we found a significantly higher mortality rate
in those with KF, 1 (7.9% vs 21.8%, P < .05), 2 (11.8% vs 31.5%, P < .05), and 5
years (22.3% vs 43.7%, P < .05) after the index event. There were no differences
in life-threatening arrhythmias, cardiogenic shock, cardiopulmonary
resuscitation, and thromboembolic events in both groups at the index event.
Patients with TC and KF have a much worse long-term prognosis. This is clinically
relevant, but the mechanisms responsible remain to be determined.
PMID- 28691505
TI - Impact of Chronic Kidney Disease on the Presentation and Outcome of Patients
Hospitalized With Atrial Fibrillation: Insights From Qatar.
AB - Atrial fibrillation (AF) with coexistent chronic kidney disease (CKD) is poorly
described in the literature. We compared the presenting symptoms, clinical
characteristics, treatment, and outcome of patients hospitalized with AF with and
without CKD in a large clinical registry. Data of patients hospitalized with AF
between 1991 and 2012 in Qatar were analyzed. Of 5201 patients hospitalized for
AF, 264 (5.1%) had CKD. Patients with AF and CKD were older with higher
prevalence of other comorbidities and left ventricular dysfunction and were more
likely to present with shortness of breath and chest pain compared with patients
with AF alone who were more likely to present with palpitation. The crude in
hospital mortality was 3 times higher in patients with dual disease. On
multivariable adjustments, CKD was an independent predictor of mortality (odds
ratio: 2.84; 95% confidence interval: 1.33-6.08, P = .001). Further studies are
warranted to try to reduce the increased mortality observed in this high-risk
population.
PMID- 28691506
TI - The effect of music therapy on cognitive functions in patients with dementia: a
systematic review and meta-analysis.
AB - OBJECTIVES: The aim of the present study was to meta-analyze the effect of music
therapy (MT) on cognitive functions in patients with dementia. METHOD: A
systematic literature search was performed in Medline, PsycINFO, Embase, CINAHL
and RILM up to 8 September 2016. We included all randomized controlled trials
that compared MT with standard care, or other non-musical types of intervention,
evaluating cognitive outcomes in patients with dementia. Outcomes included global
cognition, complex attention, executive function, learning and memory, language,
and perceptual-motor skills. RESULTS: From 1089 potentially relevant records, 110
studies were assessed for eligibility, and 7 met the inclusion criteria, of which
6 contained appropriate data for meta-analysis (330 participants, mean age range
78.8-86.3). Overall, random-effects meta-analyses suggested no significant
effects of MT on all outcomes. Subgroup analysis found evidence of a beneficial
effect of active MT on global cognition (SMD = 0.29, 95% CI 0.02 to 0.57, p =
0.04). CONCLUSION: Despite the limited evidence of the present review, it is
important to continue supporting MT as a complementary treatment for older adults
with dementia. RCTs with larger sample sizes are needed to better elucidate the
impact of MT on cognitive functions.
PMID- 28691507
TI - Genetic Basis of Positive and Negative Symptom Domains in Schizophrenia.
AB - Schizophrenia is a highly heritable disorder, the genetic etiology of which has
been well established. Yet despite significant advances in genetics research, the
pathophysiological mechanisms of this disorder largely remain unknown. This gap
has been attributed to the complexity of the polygenic disorder, which has a
heterogeneous clinical profile. Examining the genetic basis of schizophrenia
subphenotypes, such as those based on particular symptoms, is thus a useful
strategy for decoding the underlying mechanisms. This review of literature
examines the recent advances (from 2011) in genetic exploration of positive and
negative symptoms in schizophrenia. We searched electronic databases PubMed, Web
of Science, and Cumulative Index to Nursing and Allied Health Literature using
key words schizophrenia, symptoms, positive symptoms, negative symptoms,
cognition, genetics, genes, genetic predisposition, and genotype in various
combinations. We identified 115 articles, which are included in the review.
Evidence from these studies, most of which are genetic association studies,
identifies shared and unique gene associations for the symptom domains. Genes
associated with neurotransmitter systems and neuronal development/maintenance
primarily constitute the shared associations. Needed are studies that examine the
genetic basis of specific symptoms within the broader domains in addition to
functional mechanisms. Such investigations are critical to developing precision
treatment and care for individuals afflicted with schizophrenia.
PMID- 28691508
TI - Substantial improvement of primary cardiovascular prevention by a systematic
score-based multimodal approach: A randomized trial: The PreFord-Study.
AB - : Trial design Prospective randomized multicentre interventional study. Methods
Individual cardiovascular risk assessment in Ford Company, Germany employees ( n
= 4.196), using the European Society of Cardiology-Systematic Coronary Risk
Evaluation (ESC-SCORE) for classification into three risk groups. Subjects
assigned to ESC high-risk group (ESC-SCORE >= 5%), without a history of
cardiovascular disease were eligible for randomization to a multimodal 15-week
intervention programme (INT) or to usual care and followed up for 36 months.
Objectives Evaluation of the long-term effects of a risk-adjusted multimodal
intervention in high-risk subjects. Primary endpoint: reduction of ESC-SCORE in
INT versus usual care. Secondary endpoints: composite of fatal and non-fatal
cardiovascular events and time to first cardiovascular event. STATISTICAL
ANALYSIS: intention-to-treat and per-protocol analysis. Results Four hundred and
forty-seven subjects were randomized to INT ( n = 224) or to usual care ( n =
223). After 36 months ESC-SCORE development favouring INT was observed (INT:
8.70% to 10.03% vs. usual care: 8.49% to 12.09%; p = 0.005; net difference:
18.50%). Moreover, a significant reduction in the composite cardiovascular events
was observed: (INT: n = 11 vs. usual care: n = 27). Hazard ratio of intervention
versus control was 0.51 (95% confidence interval 0.25-1.03; p = 0.062) in the
intention-to-treat analysis and 0.41 (95% confidence interval 0.18-0.90; p =
0.026) in the per-protocol analysis, respectively. No intervention-related
adverse events or side-effects were observed. Conclusions Our results demonstrate
the efficiency of identifying cardiovascular high-risk subjects by the ESC-SCORE
in order to enrol them to a risk adjusted primary prevention programme. This
strategy resulted in a significant improvement of ESC-SCORE, as well as a
reduction in predefined cardiovascular endpoints in the INT within 36 months.
(ISRCTN 23536103.).
PMID- 28691510
TI - Treatment of Pseudobulbar Affect With Fluoxetine and Dextromethorphan in a Woman
With Multiple Sclerosis.
PMID- 28691509
TI - Content of Orthopedic Patient Education Provided by Nurses in Seven European
Countries.
AB - Patients' and their significant others' education during the perioperative phase
is an important and challenging aspect of care. This study explored the content
of education provided by nurses to arthroplasty patients and their significant
others. Data were collected with the Education of Patients-NURSE content (EPNURSE
Content), Received Knowledge of Hospital Patient (RKhp), and Received Knowledge
of Significant Other (RKso) scales. The results showed that the content of
education emphasized biophysiological and functional needs, differed between
countries, and was related to how physically demanding nurses found their job to
be and the amount of education provided. There is congruence between the received
knowledge of patients and their significant others in relation to the content of
education provided by nurses. The findings can support nurses in developing aid
material for patients and significant others explaining the nature of education
and advising them what to expect and how to optimize their participation in the
process.
PMID- 28691511
TI - Defining a stable water isotope framework for isotope hydrology application in a
large trans-boundary watershed (Russian Federation/Ukraine).
AB - Stable isotopes of hydrogen (2H) and oxygen (18O) of the water molecule were used
to assess the relationship between precipitation, surface water and groundwater
in a large Russia/Ukraine trans-boundary river basin. Precipitation was sampled
from November 2013 to February 2015, and surface water and groundwater were
sampled during high and low flow in 2014. A local meteoric water line was defined
for the Ukrainian part of the basin. The isotopic seasonality in precipitation
was evident with depletion in heavy isotopes in November-March and an enrichment
in April-October, indicating continental and temperature effects. Surface water
was enriched in stable water isotopes from upstream to downstream sites due to
progressive evaporation. Stable water isotopes in groundwater indicated that
recharge occurs mainly during winter and spring. A one-year data set is probably
not sufficient to report the seasonality of groundwater recharge, but this survey
can be used to identify the stable water isotopes framework in a weakly gauged
basin for further hydrological and geochemical studies.
PMID- 28691512
TI - The Incidence of Complex Regional Pain Syndrome in Simultaneous Surgical
Treatment of Carpal Tunnel Syndrome and Dupuytren Contracture.
AB - BACKGROUND: To determine the incidence of complex regional pain syndrome (CRPS)
in the concurrent surgical treatment of Dupuytren contracture (DC) and carpal
tunnel syndrome (CTS) through a thorough review of evidence available in the
literature. METHODS: The indices of 260 hand surgery books and PubMed were
searched for concomitant references to DC and CTS. Studies were eligible for
inclusion if they evaluated the outcome of patients treated with simultaneous
fasciectomy or fasciotomy for DC and carpal tunnel release using CRPS as a
complication of treatment. Of the literature reviewed, only 4 studies met the
defined criteria for use in the study. Data from the 4 studies were pooled, and
the incidence of recurrence and complications, specifically CRPS, was noted.
RESULTS: The rate of CRPS was found to be 10.4% in the simultaneous treatment
group versus 4.1% in the fasciectomy-only group. This rate is nearly half the
8.3% rate of CRPS found in a randomized trial of patients undergoing carpal
tunnel release. CONCLUSIONS: Our analysis demonstrates a marginal increase in the
occurrence of CRPS by adding the carpal tunnel release to patients in need of
fasciectomy, contradicting the original reports demonstrating a much higher rate
of CRPS. This indicates that no clear clinical risk is associated with
simultaneous surgical treatment of DC and CTS. In some patients, simultaneous
surgical management of DC and CTS can be accomplished safely with minimal
increased risk of CRPS type 1.
PMID- 28691513
TI - Use of social networking sites and associations with skin tone dissatisfaction,
sun exposure, and sun protection in a sample of Australian adolescents.
AB - OBJECTIVE: Previous research has indicated that greater exposure to traditional
media (i.e. television, film, and print) predicted skin cancer risk factors in
adolescents; however, the relationship between social media usage and these
outcomes remains unexplored. We examined whether social networking site (SNS)
usage, and the particular manner of this use, was associated with skin tone
dissatisfaction, sun exposure and sun protection among Australian adolescents. We
also explored sex differences in SNS usage related to tanning. METHOD: A total of
1856 South Australian secondary school students completed the Australian School
Students Alcohol and Drug 2014 survey. SNS usage related to tanning comprised
posting pictures, posting text, viewing pictures, viewing text and liking or
sharing posts. RESULTS: Adolescents spent 214.56 minutes, on average, per day
using SNSs. Behaviours related to tanning that involved pictures (i.e. viewing
pictures, posting pictures, and liking or sharing content) were significantly
associated with more skin tone dissatisfaction, more sun exposure and less sun
protection. Females performed all SNS-linked behaviours more frequently than did
males, with the exception of posting text. CONCLUSION: Australian adolescents
spend a considerable amount of time using SNSs, and their behaviours related to
tanning on these SNSs are significantly associated with skin cancer risk factors.
PMID- 28691514
TI - Effect of heat treatment to sweet potato flour on dough properties and
characteristics of sweet potato-wheat bread.
AB - The effect of heat treatment at 90, 100, 110 and 120 C for 20 min to sweet potato
flour on dough properties and characteristics of sweet potato-wheat bread was
investigated. The lightness (L*) and a* of sweet potato flour samples after heat
treatment were increased, while the b* were decreased significantly, as well as
the particle size, volume and area mean diameter ( p < 0.05). A slight change of
the microstructures of sweet potato flour was observed, where the number of
irregular granules increased as the temperature increased from 90 to 120 C.
Compared with sweet potato flour samples without heat treatment and with heat
treatment at 90, 100 and 120 C, the gelatinization temperature and enthalpy
change of sweet potato flour at 110 C were the lowest, which were 77.94 C and
3.67 J/g, respectively ( p < 0.05). After heat treatment, gas retention of the
dough with sweet potato flour increased significantly from 1199 ml without heat
treatment to 1214 ml at 90 C ( p < 0.05). In addition, specific loaf volume of
sweet potato-wheat bread with sweet potato flour after heat treatment increased
significantly, which was the largest at 90 C (2.53 cm3/g) ( p < 0.05). Thus, heat
treatment at 90 C to sweet potato flour could be potentially used in wheat bread
production.
PMID- 28691515
TI - Anxiety, age, education and activities of daily living as predictive factors of
the occurrence of frailty syndrome in patients with heart rhythm disorders.
AB - OBJECTIVES: Frailty is one of the geriatric syndromes that are caused by
subclinical impairment of many organs, leading to the loss of reserves and the
ability to maintain homeostasis. Aim of the study was to assess which factors
including anxiety and depression can be predictive factors for the occurrence of
frailty syndrome in patients with heart rhythm disorders. METHODS: The study
included 171 consecutive patients >64 years (73.91 +/- 6.72; 48.5% W) with
diagnosed cardiac arrhythmias who had been qualified for pacemaker implantation.
The Tilburg Frailty Indicator scale as well as the Hospital Anxiety and Depresion
Scale (HADS) were used. RESULTS: The average HADS results in the frailty group
was significantly higher 7.42 +/- 2.63 compared to the robust patients 6.33 +/-
2.83; p =0.0019. Similar results were observed in patients with atrio-ventricular
blocks (AVB): HADS-A: frail 8.23 +/- 2.13 vs. robust 6.62 +/- 2.27; p = 0.0036
and HADS-D: frail 8.84 +/- 2.85 vs. robust 7.17 +/- 2.48; p =0.0086. The multiple
regression model showed that age (p =0.0023), education (p =0.0001), ADL (p
=0.0001) and the severity of the anxiety (p = 0.0414) were important predictors
of the dependent variable and predicted higher levels of frailty syndrome.
CONCLUSION: Anxiety, age, education and the activities of daily living can be
predictive factors of the occurrence of frailty syndrome in patients with heart
rhythm disorders who have been qualified for pacemaker implantation.
PMID- 28691516
TI - Excessive daytime sleepiness in chronic migraine and chronic tension-type
headache from the general population.
AB - Introduction A relationship between headache and excessive daytime sleepiness
(EDS) has been suggested. This study investigated this association in relation to
people with chronic migraine or chronic tension-type headaches. Methods A total
of 30,000 persons aged 30-44 from the general population were screened for
chronic headache. Those eligible were interviewed by a headache specialist. EDS
was defined as Epworth sleepiness scale score >10. Logistic regression models
were used. Results Among the 323 eligible participants, 21.1% had EDS. In
multivariable logistic regression analysis, the odds ratios (OR) of EDS were not
significantly different in people with CM and CTTH. However, high headache
frequency was associated with EDS (OR 2.03 (95% CI 1.11-3.73, p = 0.022)) for
those with >= 80 compared to < 80 headache days/3 months, after adjustment for
type of headache, age, and gender. Conclusions Increased EDS was associated with
higher headache frequency, but not with specific headache diagnoses.
PMID- 28691517
TI - Migraine triggers and habituation of visual evoked potentials.
AB - Background Identifying specific subsets of patients within the clinical spectrum
of migraine could help in personalizing migraine treatment. Profiling patients by
combining clinical characteristics and neurophysiological biomarkers is largely
unexplored. We studied the association between migraine attack triggers and
habituation of visual evoked potentials. Methods We personally interviewed 25
patients about their migraine triggers following a structured list, and measured
the N1-P1 habituation slope over six blocks of 100 averaged pattern-reversal VEP
afterwards. Results The mean number of triggers per patient was 4.52 +/- 1.42.
Habituation slopes differed significantly between subjects who reported stress as
a migraine trigger (deficient VEP habituation) and subjects who did not
(preserved VEP habituation). For the remaining categories, the mean amplitude
slope was always positive, indicating deficient habituation, and was not
significantly different between subgroups. Conclusions Migraine patients not
reporting perceived stress as a trigger for their attacks might constitute a
distinct clinic-physiological subset within the migraine spectrum.
PMID- 28691518
TI - Typical pain experience but underestimation of others' pain: Emotion perception
in self and others in autism spectrum disorder.
AB - Difficulties in emotion perception are commonly observed in autism spectrum
disorder. However, it is unclear whether these difficulties can be attributed to
a general problem of relating to emotional states, or whether they specifically
concern the perception of others' expressions. This study addressed this question
in the context of pain, a sensory and emotional state with strong social
relevance. We investigated pain evaluation in self and others in 16 male
individuals with autism spectrum disorder and 16 age- and gender-matched
individuals without autism spectrum disorder. Both groups had at least average
intelligence and comparable levels of alexithymia and pain catastrophizing. We
assessed pain reactivity by administering suprathreshold electrical pain
stimulation at four intensity levels. Pain evaluation in others was investigated
using dynamic facial expressions of shoulder patients experiencing pain at the
same four intensity levels. Participants with autism spectrum disorder evaluated
their own pain as being more intense than the pain of others, showing an
underestimation bias for others' pain at all intensity levels. Conversely, in the
control group, self- and other evaluations of pain intensity were comparable and
positively associated. Results indicate that emotion perception difficulties in
autism spectrum disorder concern the evaluation of others' emotional expressions,
with no evidence for atypical experience of own emotional states.
PMID- 28691519
TI - The role of stressful life events on the cortisol reactivity patterns of breast
cancer survivors.
AB - OBJECTIVE: Atypical patterns of cortisol secretion following an acute stressor
have been commonly reported in breast cancer survivors. Stressful life events
have been associated with blunted acute cortisol levels in other populations. The
purpose of this study was to explore the role of stressful life events on
cortisol secretion patterns of breast cancer survivors following an acute
stressor. DESIGN: The Trier Social Stress (TSST) was used to elicit a moderate
stress response in breast cancer survivors (n = 19) and a control group (n = 17).
Saliva samples were collected before, during and after the TSST to provide
cortisol concentrations. During recovery, we recorded the frequency and
subjective impact of stressful life events in the past year using the Life
Experience Survey. RESULTS: Simple regressions analyses were performed; results
suggest no group differences between the total number of stressful life events
and their subjective impact. However, the total number of stressful life events
as well as their subjective impact correlated negatively with the peak cortisol
concentration in breast cancer survivors. CONCLUSIONS: The cumulative effect of
stressful life events, positive and negative, may impact the endocrine stress
system of breast cancer survivors more so than that of women with no history of
cancer.
PMID- 28691520
TI - Caring For Me and You: the co-production of a computerised cognitive behavioural
therapy (cCBT) package for carers of people with dementia.
AB - OBJECTIVES: Carers of people with dementia face barriers in accessing therapy for
mental health difficulties. Computerised cognitive behavioural therapy (cCBT)
packages can be effective in treating a range of presentations; however, tailored
packages for carers' unique needs are lacking. Our aim was to design a cCBT
package for carers to address the limitations of previous online interventions,
by including users and experts as consultants and collaborators throughout the
project. METHOD: We adopted a three-phase approach to the development process.
Firstly, a data-gathering phase in which current literature and best practice was
reviewed, and semi-structured interviews conducted with service users, academic
and clinical experts. Secondly, a co-production and refinement phase with carers
testing materials and providing feedback. Thirdly, a pilot field testing phase of
service users and the research team testing the package. RESULTS: The 'Caring For
Me and You' package adopted a transdiagnostic approach to take account of the
range of difficulties that carers face. The package consisted of 20 short
sessions with features built in to engage users and personalise content to meet
individuals' needs. CONCLUSION: User involvement was central to the design of the
'Caring For Me and You' package which is currently being evaluated in a three-arm
randomised controlled trial.
PMID- 28691521
TI - 15-deoxy-isoxeniolide-A, new diterpenoid from a bornean soft coral, Xenia sp.
AB - A new xenicane diterpenoid, 15-deoxy-isoxeniolide-A (1) along with four known
compounds 9-deoxy-isoxeniolide-A (2), isoxeniolide-A (3), xeniolide-A (4) and
coraxeniolide-B (5) were isolated from the Bornean soft coral Xenia sp. The
structures of these metabolites were elucidated on the basis of spectral
analysis, NMR and HRESIMS. Compound 5 showed cytotoxic activity against ATL cell
line, S1T.
PMID- 28691522
TI - The rate of mental health service use in New Zealand as analysed by ethnicity.
AB - OBJECTIVES: To compare by ethnicity the rates of apparent new referrals and
admissions to mental health services for selected major diagnostic groupings.
METHOD: Using a Ministry of Health database covering all referrals and admissions
to New Zealand's Mental Health services in 2014 and who had not been patients in
the preceding six years, population adjusted rates of presentation were
calculated and compared across the two major New Zealand ethnic groupings.
RESULTS: Population corrected rates of apparently new cases of schizophrenia are
more than twice as common in Maori as in non-Maori. Major depression is also
significantly more common in Maori. That same trend was not evident for bipolar
patients. CONCLUSIONS: These ethnically associated apparent differences in the
rates of schizophrenia and depression need both confirmation and explanation.
PMID- 28691523
TI - Reflections of a psychiatric mercenary: on being a locum.
AB - OBJECTIVE: In this article I reflect on life as a locum psychiatrist in Australia
and New Zealand, considering the context, qualities required in a locum and the
benefits and challenges of the role. CONCLUSIONS: Australasian psychiatric locums
work mostly in rural areas or small towns where it is difficult to recruit and
retain consultants or to cover for leave. The qualities appreciated in locums are
their presence, the ability to start work quickly, flexibility, therapeutic
caution and advocacy. The personal benefits are income, adventure and learning.
While there are difficulties and frustrations, being a locum is interesting and
exciting for those inclined to step out of their comfort zone.
PMID- 28691524
TI - Dr Digby Moynagh (1911-1963) and the Graylands Day Hospital, 1959-1965.
AB - OBJECTIVE: To describe the establishment of Australia's first psychiatric day
hospital in Western Australia in April 1959 by Dr Digby Moynagh (1911-1963).
METHODS: A range of primary and secondary sources were consulted. RESULTS:
Moynagh was able to establish the Graylands Day Hospital because he had an
outsider's perspective, and was familiar with the day hospital model from UK
psychiatric literature. However, he was opposed by local medical and political
interests, which eventually led to his departure from the State. CONCLUSIONS: The
Graylands Day Hospital and Digby Moynagh both contributed towards the process of
psychiatric deinstitutionalisation in Australia.
PMID- 28691525
TI - Diagnostic performance of CT-guided percutaneous transthoracic core needle biopsy
using low tube voltage (100 kVp): comparison with conventional tube voltage (120
kVp).
AB - Background Computed tomography (CT)-guided percutaneous transthoracic core needle
biopsy (PTNB) is typically performed at 120 kVp tube voltage. However, there is
no study that has demonstrated diagnostic performance including ground-glass
nodules and radiation dose reduction at lower tube voltage in large population.
Purpose To retrospectively compare the diagnostic performance and radiation dose
between 100 kVp and 120 kVp during CT-guided PTNB. Material and Methods This
study included 393 PTNBs performed in 385 patients (Group I; 120 kVp) from March
2011 to September 2011 and 1368 PTNBs performed in 1318 patients (Group II; 100
kVp) from October 2011 to December 2013. The patients underwent CT-guided PTNB
with the coaxial technique. Diagnostic performance, complication rate, and
radiation dose were compared between two groups. Results Technical success was
achieved in 391 of 393 PTNBs (99.5%) in Group I and in 1344 of 1368 PTNBs (98.2%)
in Group II ( P = 0.09). The diagnostic accuracies for pulmonary lesions were not
significantly different between two groups (97.1% [362/373] versus 96.2%
[1202/1249], P = 0.458). Complication rate showed no significant differences
between two groups in terms of pneumothorax (19.7% [77/391] versus 19.4%
[261/1344], P = 0.904) and hemoptysis (2.3% [9/391] versus 3.2% [43/1344], P =
0.360). Among patients who developed pneumothorax, three patients (3.9%, 3/77) in
Group I and eight patients (3.1%, 8/261) in Group II required treatment with
drainage catheter. Nobody needed further treatment for hemoptysis in the two
groups. The mean radiation dose was 1.5 +/- 1.9 mSv in Group I and 0.7 +/- 0.3
mSv in Group II ( P < 0.001). Conclusion The 100-kVp protocol for CT-guided PTNB
showed significant benefit of radiation dose reduction while maintaining high
diagnostic accuracy and safety.
PMID- 28691526
TI - Non-enhanced versus low-dose contrast-enhanced renal magnetic resonance
angiography at 7 T: a feasibility study.
AB - Background Considering the currently reported association between a repetitive
application and cumulative dosage of Gadolinium (Gd)-based contrast agents and Gd
deposition in brain tissue as well as the risk for the advent of nephrogenic
systemic fibrosis (NSF), techniques allowing for a dose reduction become an
important key aspect aside from non-enhanced magnetic resonance angiography (MRA)
techniques. Thus, this study was focused on the reduction and/or complete
omission of contrast agent for renal MRA at 7T. Purpose To evaluate the
performance of time-of-flight MRA versus low-dose contrast-enhanced (CE) renal
MRA at 7T. Material and Methods Ten healthy volunteers were examined on a 7T MR
system comprising a TOF MRA and three-dimensional (3D) fast low angle shot
spoiled gradient-echo sequence (FLASH) MRA after administration of one-quarter of
clinical dose of gadobutrol. Qualitative image analysis was performed including
overall image quality, artery delineation and presence of artifacts. Contrast
ratio (CR), signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) of the
renal arteries were calculated. Results TOF MRA and low-CE MRA achieved
comparable overall ratings, with slightly superior delineation of the main renal
arteries in TOF MRA (TOF = 3.10 +/- 0.75, low-CE = 2.95 +/- 0.75). Segmental
branches outside and inside the parenchyma were delineated significantly better
on TOF MRA. Quantitative analysis demonstrated the superiority of TOF MRA,
yielding higher scores for CR, SNR, and CNR. Conclusion The initial results of
our study demonstrate the feasibility and comparable diagnostic performance of
TOF and low-dose CE renal MRA at 7T.
PMID- 28691527
TI - Generic gadolinium-based contrast agents: the future?
PMID- 28691528
TI - Ribbing disease: a systematic review.
AB - Background Ribbing disease, or multiple diaphyseal sclerosis, is a rare benign
bone dysplasia. Purpose To systematically review the literature to determine the
clinical and radiological presentation of patients with Ribbing disease as well
as the effects of attempted treatments. Material and Methods We considered
individual patient data of patients diagnosed with Ribbing disease derived from
patient reports and patient series. All stages of the review were performed by
two reviewers independently. Standard descriptive statistics were used for
quantitative analyses and mixed model analyses were used when appropriate Results
The literature search yielded 420 unique hits of which 23 studies were included,
covering a total of 40 patients of whom 29 had bilateral involvement. The mean
age at diagnosis was 35 years and the mean time between diagnosis and onset of
symptoms, mostly pain, was five years (range = 1-16 years). The tibial diaphysis
was the most commonly involved bone in 35 of 36 patients. Non-surgical treatment
consisted of non-steroidal anti-inflammatory drugs (NSAIDs), prednisone, and
bisphophonates with mixed results. Surgical treatment consisted of intramedullary
reaming and fenestration and was very effective to reduce pain. Conclusion The
clinical presentation and imaging findings of patients with Ribbing disease are
becoming more apparent. However, there is paucity of evidence on the natural
disease progression and effectiveness of treatment modalities.
PMID- 28691529
TI - Percutaneous treatment of hepatic hydatid cysts is safe and effective with low
profile single step trocar catheter.
PMID- 28691530
TI - Depressive symptoms in Parkinson's disease are related to decreased left
hippocampal volume: correlation with the 15-item shortened version of the
Geriatric Depression Scale.
AB - Background The relationship between hippocampal and amygdaloid volumes and
depression in patients with Parkinson's disease (PD) is a controversial issue.
Purpose To investigate the correlation between the 15-item shortened version of
the Geriatric Depression Scale (GDS-15) and gray matter volume in PD. Material
and Methods In the present study, 46 participants with PD were scanned with 3 T
magnetic resonance imaging (MRI) to obtain three-dimensional (3D) T1-weighted
(T1W) images. Neurologists specializing in movement disorders performed clinical
evaluations of the participants (e.g. GDS-15, Mini-Mental State Examination, PD
duration, age, sex). Statistical Parametric Mapping 8 software was used for image
gray matter segmentation and for a correlation analysis between gray matter
volume and GDS-15 score. Results The results showed a significant negative
correlation between GDS-15 score and left hippocampal volume, and between GDS-15
score and right parahippocampal gyrus volume. No significant positive
correlations were found in the whole brain. Conclusion The current results
provide new evidence regarding the relationship between depression in PD and
hippocampal volume.
PMID- 28691531
TI - Survival analysis of the Wallis interspinous spacer used as an augment to lumbar
decompression.
AB - OBJECT: The Wallis fixed interspinous spacer may augment traditional
decompression in the treatment of lumbar spinal stenosis. The aim of this study
was to determine factors influencing survival of the Wallis interspinous spacer
and to identify specific modes and predictors of failure. METHODS: We performed a
retrospective cohort study of 244 Wallis interspinous spacers implanted in 195
consecutive patients with a mean age of 56 years (range 21-87) to augment single
or multi-level decompression. We examined patient demographics, indications for
surgery, surgical techniques and pathology on magnetic resonance imaging (MRI). A
Kaplan-Meier survival analysis was performed. RESULTS: Median follow-up was 4.5
years (range 2-8). Sixteen patients were lost to follow-up. Repeat MRI was
performed in 98 patients (50%). A recurrent stenosis was found in 21% of patients
(41/195) and occurred at a similar incidence at the level of the spacer and at
adjacent spinal levels. Revision decompression was performed in 19 patients (10%)
at 2.8 +/- 1.8 years (range 6 months-6 years) with implant removal in 15 and
conversion to fusion in 4 patients. No specific patient factors or pre-operative
MRI findings predicted failure. Five-year survival was 91% (95% CI: 79-96%).
CONCLUSIONS: The Wallis implant is generally implanted without complication when
used as an adjunct to decompression with a good medium term survival. Though disc
heights were maintained, the Wallis spacer did not however appear to reduce the
incidence of recurrent spinal or foraminal stenosis from that expected from
decompression alone.
PMID- 28691532
TI - Is the effect of coping styles disease specific? Relationships with emotional
distress and quality of life in acquired brain injury and multiple sclerosis.
AB - OBJECTIVE: To investigate the use of coping styles and the relationships linking
coping to emotional distress and quality of life in patients with acquired brain
injury and multiple sclerosis. METHOD: Cross-sectional cohort study of 143
patients with acquired brain injury and 310 patients with multiple sclerosis in
the chronic stage. Quality of life was measured with the Life Satisfaction
Questionnaire (LiSat-9), coping styles with the Coping Inventory for Stressful
Situations (CISS-T, task-oriented; CISS-E, emotion-oriented; CISS-A, avoidance),
emotional distress with the Hospital Anxiety and Depression Scale (HADS).
RESULTS: Coping styles did not differ between types of multiple sclerosis and
varied only little with regard to severity of disease. In both patient groups,
task-oriented coping was most used followed by avoidance and emotion-oriented
coping. Patients with multiple sclerosis used all styles to a greater extent. In
acquired brain injury, lower CISS-E and lower HADS scores were associated with
higher LiSat-9 scores. CISS-E had a direct effect on LiSat-9 and an indirect
effect via HADS. In multiple sclerosis, next to lower CISS-E and lower HADS
scores, higher CISS-A scores were also associated with higher LiSat-9 scores.
CISS-E had an indirect effect and CISS-A had a direct and indirect effect on
LiSat-9. CONCLUSION: In both patient groups, coping patterns are similar, and
emotion-oriented coping negatively influences quality of life. Additionally, in
multiple sclerosis, seeking emotional support and distraction (CISS-A) was
positively associated with quality of life. Interventions to improve adaptive
coping could be organized within a neurorehabilitation setting for both patient
groups together.
PMID- 28691533
TI - Correction to: Zhang etal., Comparison of pharmacokinetics and drug release in
tissues after transarterial chemoembolization with doxorubicin using diverse
lipiodol emulsions and CalliSpheres Beads in rabbit livers.
PMID- 28691534
TI - Relative survival and excess mortality following primary percutaneous coronary
intervention for ST-elevation myocardial infarction.
AB - BACKGROUND: High survival rates are commonly reported following primary
percutaneous coronary intervention for ST-elevation myocardial infarction, with
most contemporary studies reporting overall survival. AIMS: The aim of this study
was to describe survival following primary percutaneous coronary intervention for
ST-elevation myocardial infarction corrected for non-cardiovascular deaths by
reporting relative survival and investigate clinically significant factors
associated with poor long-term outcomes. METHODS AND RESULTS: Using the
prospective UK Percutaneous Coronary Intervention registry, primary percutaneous
coronary intervention cases ( n=88,188; 2005-2013) were matched to mortality data
for the UK populace. Crude five-year relative survival was 87.1% for the patients
undergoing primary percutaneous coronary intervention and 94.7% for patients <55
years. Increasing age was associated with excess mortality up to four years
following primary percutaneous coronary intervention (56-65 years: excess
mortality rate ratio 1.61, 95% confidence interval 1.46-1.79; 66-75 years: 2.49,
2.26-2.75; >75 years: 4.69, 4.27-5.16). After four years, there was no excess
mortality for ages 56-65 years (excess mortality rate ratio 1.27, 0.95-1.70), but
persisting excess mortality for older groups (66-75 years: excess mortality rate
ratio 1.72, 1.30-2.27; >75 years: 1.66, 1.15-2.41). Excess mortality was
associated with cardiogenic shock (excess mortality rate ratio 6.10, 5.72-6.50),
renal failure (2.52, 2.27-2.81), left main stem stenosis (1.67, 1.54-1.81),
diabetes (1.58, 1.47-1.69), previous myocardial infarction (1.52, 1.40-1.65) and
female sex (1.33, 1.26-1.41); whereas stent deployment (0.46, 0.42-0.50)
especially drug eluting stents (0.27, 0.45-0.55), radial access (0.70, 0.63-0.71)
and previous percutaneous coronary intervention (0.67, 0.60-0.75) were
protective. CONCLUSIONS: Following primary percutaneous coronary intervention for
ST-elevation myocardial infarction, long-term cardiovascular survival is
excellent. Failure to account for non-cardiovascular death may result in an
underestimation of the efficacy of primary percutaneous coronary intervention.
PMID- 28691535
TI - Promoting free flow in the networks: Reimagining the body in early modern Suzhou.
AB - The history of Chinese medicine is still widely imagined in terms dictated by the
discourse of modernity, that is as 'traditional' and 'Chinese.' And yet, so as to
be intelligible to us moderns, it must simultaneously be framed through
categories that make it comparable somehow to the 'West' and the 'modern' from
which it is said to be essentially different. This is accomplished, for instance,
by viewing Chinese medicine as fundamentally shaped by cosmological thinking, as
focusing on process rather than matter, and as forever hampered by attachments to
the past even when it tries to innovate. At the same time, it is described as
pursuing its objectives in ways that make sense in 'our' terms, too, such as the
goal of creating physiological homeostasis through methods of supplementation and
drainage. In this paper, I seek to move beyond this kind of analysis through a
two-pronged approach. First, by focusing on the concept of tong - a character
that calls forth images of free flow, connectivity, relatedness and understanding
- I foreground an important aspect of Chinese medical thinking and practice that
has virtually been ignored by Western historians of medicine and science. Second,
by exploring how the influential physician Ye Tianshi (1664-1746) employed tong
to advance medical thinking and practice at a crucial moment of change in the
history of Chinese medicine, I demonstrate that physicians in early modern China
moved towards new understandings of the body readily intelligible by modern
biomedical anatomy. I argue that this mode of analysis allows us to transcend the
limitations inherent in the current historiography of Chinese medicine: because
it allows for comparison to emerge from our subject matter rather than imposing
our imaginaries onto it in advance.
PMID- 28691536
TI - MABp1 for the treatment of colorectal cancer.
AB - INTRODUCTION: Inflammation is an established process in colorectal cancer
development and a hallmark of progression, and pro-inflammatory cytokines have
been implicated in the morbidity and functional compromise associated with
malignancy. MABp1, described as a first-in-class true human antibody against
interleukin-1alpha, has undergone clinical trial evaluation in a number of
indications, recently completing late phase clinical trial testing under Fast
Track designation for cancer anorexia-cachexia syndrome in colorectal cancer
patients. To date, MABp1 has been evaluated as a novel therapeutic strategy to
ameliorate phenotypic factors associated with poor prognosis in colorectal cancer
patients. Areas covered: In this review, the authors discuss the clinical trial
data available to date for this antibody in colorectal cancer, including novel
clinical trial endpoints utilized to evaluate sarcopenia and inflammation, as
well as the proposed role of interleukin-1alpha antagonism in leading to improved
patient outcomes. Expert opinion: There is a multitude of antibodies in
therapeutic development in oncology, and MABp1 is a novel class of antibody which
has been safely tolerated to date. Clinical studies of this agent suggest a
significant improvement in lean body mass, though additional results evaluating
the impact of targeting inflammation as a strategy to delay disease progression
in this population are awaited.
PMID- 28691537
TI - Pharmacological management of dermatomyositis.
AB - INTRODUCTION: Dermatomyositis is a rare heterogeneous systemic autoimmune disease
with multiple organ involvement which can result in significant disability and
mortality. Despite the lack of placebo-controlled trials, glucocorticoids are
considered to be the mainstay of initial management. Treatment strategies are
mainly based on uncontrolled studies, evidence based guidelines for treatments do
not exist. Areas covered: This review provides an overview of the currently
available pharmacological treatments in the field of dermatomyositis including
conventional immunosuppressants, biologics and topical agents. The role of
antibodies in different treatment responses of dermatomyositis related
clinicoserological syndromes is also discussed. A PubMed search was performed in
order to find relevant literature for this review. Expert commentary: Early
recognition and intervention is essential to ameliorate disease outcome.
Determination of antibodies provide a useful key in diagnosis, clinical
manifestations, malignancy, prognosis, and treatment response and may lead to
wider acceptance of personalized medicine. Corticosteroids with adjunctive
steroid-sparing immunosuppressive therapies are recommended to treat disease
activity, prevent mortality, and reduce long-term disability. Combinations of
second-line therapies or newer third-line therapies are used in severe,
refractory, or corticosteroid-dependent diseases. Further research is required to
assess the role of new therapies.
PMID- 28691538
TI - Olaratumab for soft tissue sarcoma.
AB - INTRODUCTION: Soft tissue sarcomas (STS) are rare malignant tumors.
Unfortunately, the first-line doxorubicin-based treatment has not been improved
since the 1970s. Platelet-derived growth factor (PDGF) receptor alpha (PDGFR
alpha) and its ligands are co-expressed in many types of cancer, including
sarcomas. They are involved in stimulating growth and regulating stromal-derived
fibroblasts and angiogenesis. PDGFR-alpha and its ligand may play an important
role in tumorigenesis and be a potential target in the treatment of sarcomas.
Olaratumab is a fully human IgG1-type anti-PDGFR-alpha monoclonal antibody with a
high affinity and a low 50% inhibitory concentration (IC50). Areas covered: The
authors review the role of olaratumab in the treatment of STS by focusing on the
recent, randomized Phase II JDGD trial that challenged patients with unresectable
or metastatic STS with doxorubicin in the presence or absence of olaratumab. This
trial showed a great improvement in overall survival (OS), with an increase in
survival from 14.7 months to 26.5 months for patients in the experimental arm and
showed acceptable toxicity. Expert opinion: Results seem promising. However, it
must be qualified, as the study includes several uncertainties. These
uncertainties should be addressed by the ongoing Phase 3 JGDJ confirmatory trial,
for which the final efficacy analysis is expected by 2019.
PMID- 28691539
TI - Investigational antiarrhythmic agents: promising drugs in early clinical
development.
AB - INTRODUCTION: Although there have been important technological advances for the
treatment of cardiac arrhythmias (e.g., catheter ablation technology),
antiarrhythmic drugs (AADs) remain the cornerstone therapy for the majority of
patients with arrhythmias. Most of the currently available AADs were coincidental
findings and did not result from a systematic development process based on known
arrhythmogenic mechanisms and specific targets. During the last 20 years, our
understanding of cardiac electrophysiology and fundamental arrhythmia mechanisms
has increased significantly, resulting in the identification of new potential
targets for mechanism-based antiarrhythmic therapy. Areas covered: Here, we
review the state-of-the-art in arrhythmogenic mechanisms and AAD therapy.
Thereafter, we focus on a number of antiarrhythmic targets that have received
significant attention recently: atrial-specific K+-channels, the late Na+
current, the cardiac ryanodine-receptor channel type-2, and the small-conductance
Ca2+-activated K+-channel. We highlight for each of these targets available
antiarrhythmic agents and the evidence for their antiarrhythmic effect in animal
models and early clinical development. Expert opinion: Targeting AADs to specific
subgroups of well-phenotyped patients is likely necessary to detect improved
outcomes that may be obscured in the population at large. In addition, specific
combinations of selective AADs may have synergistic effects and may enable a
mechanism-based tailored antiarrhythmic therapy.
PMID- 28691540
TI - Endoscopic management of foreign bodies in the upper gastrointestinal tract: a
retrospective study of 1294 cases.
AB - OBJECTIVE: To report our endoscopic outcomes and explore the effects of duration
of impaction and anesthetic methods on the endoscopic removal of foreign bodies
in the upper gastrointestinal tract. METHODS: All consecutive patients with
suspected foreign body (FB) ingestion between January 2013 and June 2016 were
enrolled. Demographic, clinical and endoscopic data were collected and analyzed.
RESULTS: A total of 1294 patients aged seven months to 94 years were enrolled.
Odynophagia (415 cases, 32.1%), FB sensation (340 cases, 26.3%) and sore throat
(267 cases, 20.1%) were the most frequent complaints. The duration of FB
impaction ranged from 4 h to over two years. Anatomically, foreign bodies were
most commonly located in the esophagus (n = 1025, 86.9%). Bony foreign bodies
comprised the majority of identified foreign bodies. The most common underlying
pathology was esophageal stricture (38 cases, 53.5%). Nearly half of the patients
(49.9%) developed complications. As the duration of impaction increased, the
success rate by endoscopy decreased (p < .001), and the complication rate
increased (p < .001). Endoscopic management under general anesthesia didn't
improve the success rate or lower the complication rate compared with topical
pharyngeal anesthesia (p = .793 and p = .085). Age >=60, duration of impaction
longer than one day, impaction in the esophagus, and sharp foreign bodies were
identified as risk factors for complications. CONCLUSIONS: Delayed flexible
endoscopy in patients, especially elderly patients, with sharp FB impactions in
the esophagus results in worse endoscopic outcomes. Endoscopic management under
general anesthesia did not improve the therapeutic results compared with topical
pharyngeal anesthesia.
PMID- 28691541
TI - Effects of hazelnuts and cocoa on vascular reactivity in healthy subjects: a
randomised study.
AB - Cocoa helps maintain endothelium-dependent vasodilation; consumption of hazelnuts
has been associated with reduced cardiovascular disease risk. This study assesses
the effects of hazelnuts and cocoa on vascular reactivity and metabolic profile.
Sixty-one healthy volunteers, examined in a randomised, controlled, two-week
intervention, received one of six breakfast integrations containing either
hazelnuts, cocoa, both or none. Consumption of unpeeled hazelnuts improved HDL
cholesterol (+7.3%, p = .01 vs. baseline, p = .02 vs. control). Brachial artery
peak systolic velocities (PSV) at rest increased with hazelnut integrations by
43.4% (p = .04 vs. control) and hazelnut-cocoa integrations by 26.4% (p = .01 vs.
control). PSV after 3-min cuff occlusion increased by 60.7% (p = .002 vs.
control) with a peeled hazelnut snack and by 64.7% with a hazelnut-cocoa
integration (p = .04 vs. control). The combination hazelnut-cocoa may act in a
synergic and protective way on cardiovascular system.
PMID- 28691542
TI - Cross-Cultural Validation of the York Measure of Quality of Intensive Behavioral
Intervention.
AB - Early intensive behavioral intervention (EIBI) is widely applied in young
children with autism spectrum disorder. Little research has addressed the
significance of adherence to EIBI practices for treatment outcomes. The York
Measure of Quality of Intensive Behavioral Intervention (YMQI) was designed to
assess EIBI quality delivery in Ontario, Canada. The objective of this study was
to examine the cross-cultural validity of the YMQI in a clinical Swedish
community sample of 30 boys and four girls with autism aged 2.5 to 6 years.
Internal consistency was alpha = .87 for the full scale YMQI. Interrater
reliability among three raters on 97 video-recorded therapy sequences was .71
(intraclass correlation coefficient [ICC]), and intrarater reliability of two
raters re-scoring 15 sequences after 6 months was ICC = .87. The convergent
validity of the YMQI with EIBI expert ratings was r = .49. Findings endorse the
psychometric properties of the YMQI and its usability outside of Anglo-Saxon
countries.
PMID- 28691543
TI - Volar Locking Plate Fixations for Displaced Distal Radius Fractures: An
Evaluation of Complications and Radiographic Outcomes.
AB - BACKGROUND: A volar locking plate (VLP) is the most frequently used form of
implant used for open reduction and internal fixation of distal radius fractures.
They are known to have a complication rate of up to 27%. We hypothesized that
plate design could influence complication rates. METHODS: We performed a review
of patients undergoing VLP fixation for distal radius fracture. A total of 228
patients underwent fixation with the Distal Volar Radial Anatomical (DVR) plate;
388 patients underwent fixation with the VariAx plate. Independent observers
performed blinded case note and radiographic review, to assess for the quality of
reduction, and complications for the inserted VLP. RESULTS: Mean time to surgery
was 6.0 days; mean follow-up was 17.5 weeks. Mean age was 56.5 years. The quality
of reduction was classified as anatomical (46%), good (36.3%), moderate (13.0%),
or poor (3.9%). Complications were identified in 109 patients (17%). Plate
prominence was seen in 133 patients (21%). The DVR plate was less prominent ( P <
.001) and had better overall radiographic appearances ( P = .025). Flexor tendon
complications were related to plate prominence ( P = .005). Inferior reduction
was associated with increased time to surgery ( P = .020). CONCLUSIONS: This
study highlights the importance of prompt surgery, effective fracture reduction,
and careful plate positioning to avoid volar prominence.
PMID- 28691544
TI - The effect of plant sterol-enriched turkey meat on cholesterol bio-accessibility
during in vitro digestion and Caco-2 cell uptake.
AB - This study evaluated the effect of a plant sterol-enriched turkey product on
cholesterol bio-accessibility during in vitro digestion and cholesterol uptake by
Caco-2 monolayers. Turkey products, one plant sterol-enriched (PS) and one plant
sterol-free (C), were produced in an industrial pilot plant. Before simulated
digestion, matrices were spiked with cholesterol (1:5 weight ratio of cholesterol
to plant sterol). Plant sterols were included at a concentration equivalent to
the minimum daily intake recommended by the European Food Safety Authority (EFSA)
for cholesterol lowering. After simulated digestion, the percentage of
cholesterol micellarization and uptake by Caco-2 cells in the presence of PS meat
were measured. Compared to C meat, PS meat significantly inhibited cholesterol
micellarization on average by 24% and Caco-2 cell accumulation by 10%. This study
suggests that plant sterols in meat can reduce cholesterol uptake by intestinal
epithelia and it encourages efforts to make new PS-based functional foods.
PMID- 28691545
TI - Association of the functional serotonin transporter haplotype with familial form
of obsessive compulsive disorder in Iranian patients.
AB - OBJECTIVE: Several polymorphisms have been reported in the 5-HTTLPR of the
serotonin transporter gene (SLC6A4). Family-based evidences for the association
of 5-HTTLPR polymorphisms with OCD were previously reported but results were
controversial. The present study investigated the possible correlation of SLC6A4
polymorphisms (5-HTTLPR, rs25532, rs25531) in Iranian OCD patients considering
gender, age of onset, family history of psychiatric disorders, obsessive and
compulsive subtypes and severities. METHODS: The included OCD patients fulfilled
the criteria for DSM-IV-TR whom Y-BOCS score was more than 9. Blood samples (184
cases and 192 controls) were genotyped by means of PCR-RFLP. RESULTS: Mean of Y
BOCS scores of included patients was 20.1 +/- 0.69. Rs25532 CC genotype showed
significant association with OCD in men and were detected more in the patients
reported positive family history of psychiatric disorders but the other single
loci (5-HTTLPR and rs25531) did not associate with OCD. Haplotype analysis showed
significant association of 14-A variant with OCD and revealed the association of
14-A/14-A genotype with familial form of OCD. CONCLUSIONS: The findings of this
study showed the association of SLC6A4 variants with familial form of OCD and
proposed stratified analyses in the genetic studies facilitate identification of
genetic risk factors for this heterogeneous disorder.
PMID- 28691546
TI - Procalcitonin in amniotic fluid at the time of genetic amniocentesis and preterm
delivery.
AB - PURPOSE: Procalcitonin (PCT) is an acute-phase protein that has been infrequently
studied in amniotic fluid. We sought to determine if PCT levels measured in
amniotic fluid samples at the time of genetic amniocentesis are predictive of
preterm delivery. MATERIALS AND METHODS: A retrospective cohort study was
performed on all women presenting for genetic amniocentesis between 15-23 weeks
of pregnancy at our institution from 2011 to 2013 with stored amniotic fluid
samples. PCT protein levels were measured in the samples by enzyme-linked
immunosorbent assay (ELISA). PCT levels in women who delivered less than 37 weeks
versus those who delivered at or after 37 week were compared. Mann-Whitney test
was used. RESULTS: Eighty-seven samples were available for analysis and of these
eight (9.2%) were from patients who delivered preterm. Sixty-two (70%) had PCT
levels below the lower limit of quantification, which was 25 pg/mL. Median PCT
levels did not differ between the preterm and term group [20.4 pg/mL (range 0
82.8) and 20.2 pg/mL (range 0-198.4), respectively, p = .95]. CONCLUSION: In
asymptomatic women undergoing genetic amniocentesis in this cohort, procalcitonin
levels were low to undetectable and did not correlate with risk of subsequent
preterm birth.
PMID- 28691547
TI - Reduced risk of reoperation after treatment of femoral neck fractures with total
hip arthroplasty.
AB - Background and purpose - Femoral neck fractures (FNFs) are commonly treated with
some kind of arthroplasty, but evidence on whether to use hemiarthroplasty (HA)
or total hip arthroplasty (THA) is lacking. HA reduces the risk of dislocation,
but may lead to acetabular erosion. THA implies longer surgery and increased
bleeding. THA may result in better function and health-related quality of life,
but evidence is contradictory. We compared HA and THA and in terms of revision,
reoperation and death. Patients and methods - Data were extracted from the
Swedish Hip Arthroplasty Register for 11,253 patients with acute FNF receiving
cemented HA or THA during 2008-2012. 2,902 patients with THA were matched by
propensity score matching with as many patients with HA based on age, sex, BMI,
and ASA classification. We used competing risks survival regression with
reoperation or death and revision or death as endpoints. Results - THA patients
had significantly reduced risk of revision (absolute risk reduction 0.51; 95% CI
0.39-0.67) and reoperation (0.58; 0.46-0.74). THA was associated with an almost
50% reduced mortality (risk ratio as competing risk for reoperation 0.51; 0.46
0.57). Interpretation - In our national register study of femoral neck fractures,
THA had a lower risk than HA for further surgical procedures related to the hip.
The reasons for lower mortality after THA are not known. Despite matching, there
might be a selection of more healthy patients for this procedure, and other
factors unknown to us, with or without relation to the choice of implant.
PMID- 28691548
TI - Characterizing chronic and acute health risks of residues of veterinary drugs in
food: latest methodological developments by the joint FAO/WHO expert committee on
food additives.
AB - The risk assessment of residues of veterinary drugs in food is a field that
continues to evolve. The toxicological end-points to be considered are becoming
more nuanced and in light of growing concern about the development of
antimicrobial resistance, detailed analysis of the antimicrobial activity of the
residues of veterinary drugs in food is increasingly incorporated in the
assessment. In recent years, the Joint FAO/WHO Expert Committee on Food Additives
(JECFA) has refined its approaches to provide a more comprehensive and fit-for
purpose risk assessment. This publication describes in detail the consideration
of acute and chronic effects, the estimation of acute and chronic dietary
exposure, current approaches for including microbiological endpoints in the risk
assessment, and JECFA's considerations for the potential effects of food
processing on residues from veterinary drugs. JECFA now applies these approaches
in the development of health-based guidance values (i.e. safe exposure levels)
for residues of veterinary drugs. JECFA, thus, comprehensively addresses acute
and chronic risks by using corresponding estimates for acute and chronic exposure
and suitable correction for the limited bioavailability of bound residues by the
Gallo-Torres model. On a case-by-case basis, JECFA also considers degradation
products that occur from normal food processing of food containing veterinary
drug residues. These approaches will continue to be refined to ensure the most
scientifically sound basis for the establishment of health-based guidance values
for veterinary drug residues.
PMID- 28691549
TI - Factors associated with complementary and alternative medicine use among women at
midlife.
AB - Hormone replacement therapy (HRT) has been established as the first-line
treatment for women experiencing menopausal symptoms. The use of complementary
and alternative medicine (CAM), however, is becoming increasingly popular among
women at midlife for management of such symptoms. Despite the equivocal evidence
of CAM's efficacy in the reduction and alleviation of menopausal symptoms in
placebo-controlled, randomized trials, 50% of women at midlife use CAM. To date,
several large, population-based studies have focused upon CAM use amongst
menopausal women and the factors associated with the adoption of such therapies.
By identifying women in the menopausal transition who tend to use CAM, this
narrative review highlights evidence that aids women at this stage of life make
better and individualized treatment choices to relieve these symptoms. The
available evidence suggests that the prevalence of CAM use among menopausal women
is high world-wide, but there is a paucity of high-quality studies that
adequately assess the factors associated with its use. Further studies are needed
to confirm the characteristics of women who employ CAM to manage their night
sweats and hot flushes. Results of this study might enable the development of
policies catering to the needs of those women and provide a resource to support
their decision-making regarding treatment options.
PMID- 28691550
TI - Relationships between obsessive-compulsive disorder, depression and functioning
before and after exposure and response prevention therapy.
AB - OBJECTIVE: Obsessive-compulsive disorder (OCD) is associated with impaired
functioning and depression. Our aim was to examine relationships between OCD
symptoms, depression and functioning before and after exposure and response
prevention (ERP), a type of cognitive-behavioural therapy for OCD, specifically
examining whether functioning, depression and other cognitive factors like
rumination and worry acted as mediators. METHODS: Forty-four individuals with OCD
were randomised to 4 weeks of intensive ERP treatment first (n = 23) or waitlist
then treatment (n = 21). We used a bootstrapping method to examine mediation
models. RESULTS: OCD symptoms, depression and functioning significantly improved
from pre- to post-intervention. Functioning mediated the relationship between OCD
symptoms and depression and the relationship between functioning and depression
was stronger at post-treatment. Depression mediated the relationship between OCD
symptoms and functioning, but only at post-intervention. Similarly, rumination
mediated the relationship between OCD symptoms and depression at post
intervention. CONCLUSIONS: Our findings suggest that after ERP, relationships
between depression and functioning become stronger. Following ERP, treatment that
focuses on depression and functioning, including medication management for
depression, cognitive approaches targeting rumination, and behavioural activation
to boost functionality may be important clinical interventions for OCD patients.
PMID- 28691551
TI - Who Decides: Me or We? Family Involvement in Medical Decision Making in Eastern
and Western Countries.
AB - BACKGROUND: Research suggests that desired family involvement (FI) in medical
decision making may depend on cultural values. Unfortunately, the field lacks
cross-cultural studies that test this assumption. As a result, providers may be
guided by incomplete information or cultural biases rather than patient
preferences. METHODS: Researchers developed 6 culturally relevant disease
scenarios varying from low to high medical seriousness. Quota samples of
approximately 290 middle-aged urban residents in Australia, China, Malaysia,
India, South Korea, Thailand, and the USA completed an online survey that
examined desired levels of FI and identified individual difference predictors in
each country. All reliability coefficients were acceptable. Regression models met
standard assumptions. RESULTS: The strongest finding across all 7 countries was
that those who desired higher self-involvement (SI) in medical decision making
also wanted lower FI. On the other hand, respondents who valued relational
interdependence tended to want their families involved - a key finding in 5 of 7
countries. In addition, in 4 of 7 countries, respondents who valued social
hierarchy desired higher FI. Other antecedents were less consistent. CONCLUSION:
These results suggest that it is important for health providers to avoid East
West cultural stereotypes. There are meaningful numbers of patients in all 7
countries who want to be individually involved and those individuals tend to
prefer lower FI. On the other hand, more interdependent patients are likely to
want families involved in many of the countries studied. Thus, individual
differences within culture appear to be important in predicting whether a patient
desires FI. For this reason, avoiding culture-based assumptions about desired FI
during medical decision making is central to providing more effective patient
centered care.
PMID- 28691552
TI - Variations in Recruitment Yield and Characteristics of Participants Recruited
Across Diverse Internet Platforms in an HIV Testing Study of Young Adult Men-Who
Have-Sex-With-Men (YMSM).
AB - The Internet is a commonly used medium for recruiting geographically dispersed,
smaller populations quickly, such as young adult men-who-have-sex-with-men
(YMSM). One approach to improve reach and representativeness is to employ
multiple Internet platforms to recruit this hard-to-reach population. The utility
of this approach has not been studied adequately, and its impact on the study
sample recruited is not yet known. Using data from a study of 18- to 24-year-old
HIV-uninfected, Black, Hispanic, and White United States (US) YMSM, this
investigation compared advertising and enrollment metrics and participant
characteristics of those recruited across Internet platforms. Of the 2,444
participants, their median age was 22 years old; 21% were Black, 37% Hispanic,
and 42% White; 90% had been tested for HIV at least once in their life; and 87%
reported prior condomless anal intercourse (CAI) with another man. There were
noticeable differences across platforms in the number of people accessing the
study website, meeting study eligibility requirements, consenting to participate,
consenting to participate per day of advertising and per click, as well as costs
of advertising per consented participant. Participants recruited also varied
across platform by race/ethnicity, geographic area of residence in the US, health
care insurance status, years of formal education, history of HIV testing, and CAI
by partner type and sexual positioning. The investigation results indicate that
the Internet platforms used for recruitment significantly impact not only
enrollment but also diversity and characteristics of the sample obtained and
consequently, the observations and conclusions rendered.
PMID- 28691553
TI - The adverse effect of FOPNL genomic variant is reversed by bortezomib-based
treatment protocols in multiple myeloma.
AB - Fibroblast growth factor receptor 1 oncogene partner N-terminal like gene (FOPNL)
rs72773978 polymorphism was identified as an adverse prognostic factor in
multiple myeloma (MM). We aimed to investigate the associations of rs72773978
with clinical characteristics and treatment outcome in 373 Hungarian MM patients.
In our cohort, FOPNL polymorphism showed differential prognostic effect that
depended on the treatment applied. Among patients treated with non-proteasome
inhibitor (PI)-based therapy, carriership of the minor allele was significantly
associated with adverse overall survival (p=.022). In contrast, the adverse
effect was overcome by the application of PI-containing treatment (p=.048).
Multivariate analyses revealed the independent adverse effect of rs72773978 on
survival in the non-PI-treated group (p=.045), but not in PI treatment (OS:
p=.093). We confirmed the adverse prognostic effect of rs72773978 associated with
non-PI-based treatment regimens. Our results point to the importance of genotypic
prognostic information associated with complex clinical background MM.
PMID- 28691554
TI - Uptake and metabolism of carbamazepine (CBZ) by clam Ruditapes decussatus and its
effects in biochemical responses.
AB - 1. Laboratory experiments were carried out to assess uptake and metabolism of the
epilepsy drug, carbamazepine and its consequent biological responses in marine
clam (Ruditapes decussatus) a model non-target organism in ecotoxicology. 2.
Clams were exposed to two nominal concentrations (C1 = 30 MUg/L and C2 = 50
MUg/L) of CBZ for a maximum period of 14 days. Analysis of CBZ and their
metabolites in clam and water after exposure to two nominal concentrations of the
pharmaceutical drug were performed using UPLC-HRMS analysis. CBZ accumulation
reached an average tissue concentration of 1241.59 ng/g dw and 1664.33 ng/g dw at
low and high nominal concentration, respectively. 3. Furthermore, a metabolite (3
hydroxy-CBZ) was detected in tissues indicating carbamazepine translocation and
metabolism inside clam, suspect screening of CBZ glucuronides was also performed
by accurate mass extraction but it could not be detected. 4. Activities of
antioxidant enzymes superoxide dismutase, catalase and gluthatione-S-transferase
generally increased. Change in the contents of glutathione, malondialdehyde and
protein carbonyl were also studied. 5. Results indicated that the
bioaccumulation of CBZ resulted in the changes of the antioxidant defense system
and the production of ROS with the oxidative stress, ultimately induced
alteration in lipid peroxidation and protein carbonyl.
PMID- 28691555
TI - Idiopathic congenital talipes equinovarus; not always an isolated anomaly. A
review of long-term outcomes.
AB - OBJECTIVE: To describe the long-term outcomes of children at school age who were
thought to have isolated idiopathic congenital talipes equino varus (ICTEV) at
birth. METHOD: A retrospective review of all children attending a regional
talipes clinic who had achieved school age. RESULTS: One hundred sixty-three
children were followed up. ICTEV was more common in Maori and other Polynesian
children and in males. Additional abnormalities were apparent in 30.1% overall,
but higher in New Zealand Europeans (43%) than Maori (21%) or other Polynesians
(22%). Of the abnormalities, 41% were associated with the central nervous system
or with neurodevelopmental delay. Conventional G-band karyotyping, where
performed, was not informative. CONCLUSIONS: The rate of additional abnormalities
was higher than previous reports. This has implications for prenatal counseling
and postnatal follow-up as a prenatal diagnosis of ICTEV may subsequently be
found to have longer term implications in addition to orthopedic treatments of
the clubfeet.
PMID- 28691556
TI - Fluid management during the first postnatal day in very low birth weight neonates
and rates of patent ductus arteriosus requiring treatment.
AB - PURPOSE: Previous studies have suggested an association between high maintenance
fluid volumes during the first several postnatal days and patent ductus
arteriosus (PDA) requiring treatment in very low birth weight (VLBW) neonates.
However, no studies have specifically examined fluid administration during the
first postnatal day with regard to PDA-related outcomes. We seek to determine
whether additional intravenous fluid administration beyond prescribed goals
during the first postnatal day is associated with PDA requiring treatment.
MATERIALS AND METHODS: Retrospective data were collected from neonates with birth
weight <1250 g. Infants receiving fluids beyond initially documented goals,
stratified by relative degree of additional fluids, were compared to those
receiving no additional intravenous fluids for the primary outcome of PDA
requiring treatment and secondarily for other neonatal morbidities. RESULTS: Two
hundred VLBW neonates were included. Controlling for birth weight and gestational
age, fluid administration beyond prescribed goals during the first postnatal day
was not associated with increased PDA requiring treatment. Additionally, no
statistically significant associations between additional fluids and secondary
outcomes were observed. CONCLUSIONS: No significant relationship between fluid
volumes during the first postnatal day and PDA requiring treatment were observed.
Further prospective analysis of early fluid management in VLBW neonates is
warranted.
PMID- 28691557
TI - Emicizumab Prophylaxis in Hemophilia A with Inhibitors.
AB - BACKGROUND: Emicizumab (ACE910) bridges activated factor IX and factor X to
restore the function of activated factor VIII, which is deficient in persons with
hemophilia A. This phase 3, multicenter trial assessed once-weekly subcutaneous
emicizumab prophylaxis in persons with hemophilia A with factor VIII inhibitors.
METHODS: We enrolled participants who were 12 years of age or older. Those who
had previously received episodic treatment with bypassing agents were randomly
assigned in a 2:1 ratio to emicizumab prophylaxis (group A) or no prophylaxis
(group B). The primary end point was the difference in bleeding rates between
group A and group B. Participants who had previously received prophylactic
treatment with bypassing agents received emicizumab prophylaxis in group C.
RESULTS: A total of 109 male participants with hemophilia A with inhibitors were
enrolled. The annualized bleeding rate was 2.9 events (95% confidence interval
[CI], 1.7 to 5.0) among participants who were randomly assigned to emicizumab
prophylaxis (group A, 35 participants) versus 23.3 events (95% CI, 12.3 to 43.9)
among those assigned to no prophylaxis (group B, 18 participants), representing a
significant difference of 87% in favor of emicizumab prophylaxis (P<0.001). A
total of 22 participants in group A (63%) had zero bleeding events, as compared
with 1 participant (6%) in group B. Among 24 participants in group C who had
participated in a noninterventional study, emicizumab prophylaxis resulted in a
bleeding rate that was significantly lower by 79% than the rate with previous
bypassing-agent prophylaxis (P<0.001). Overall, 198 adverse events were reported
in 103 participants receiving emicizumab prophylaxis; the most frequent events
were injection-site reactions (in 15% of participants). Thrombotic
microangiopathy and thrombosis were reported in 2 participants each (in the
primary analysis) who had received multiple infusions of activated prothrombin
complex concentrate for breakthrough bleeding. No antidrug antibodies were
detected. CONCLUSIONS: Emicizumab prophylaxis was associated with a significantly
lower rate of bleeding events than no prophylaxis among participants with
hemophilia A with inhibitors. (Funded by F. Hoffmann-La Roche and Chugai
Pharmaceutical; HAVEN 1 ClinicalTrials.gov number, NCT02622321 .).
PMID- 28691558
TI - The Science of Meetings: Practical Ethicist.
PMID- 28691559
TI - Ethics and Science in the Participatory Era: A Vignette-Based Delphi Study.
AB - Participatory researchers rely on relationship-based ethical considerations to
address ethical challenges, but little is known about how these considerations
shape day-to-day decision-making. We presented vignettes describing ethical
dilemmas to health researchers with varying degrees of experience in
participatory research in an online modified-Delphi panel. Panelists rated
potential solutions to dilemmas and provided rationales for choosing solutions in
text boxes and discussion boards. Panelists agreed on a preferred solution for
three of five vignettes. Panelists indicated that ethical research decision
making should be inclusive of diverse perspectives. Panelists prioritized
scientific goals above participatory ones and viewed tenets of scientific
validity as value-free. Panelists indicated that participatory research ethics
would be difficult to codify, but that vignette-based learning could support
didactic objectives.
PMID- 28691560
TI - Bispecific Antibody Therapy in Hemophilia.
PMID- 28691561
TI - Quantification of Graph Complexity Based on the Edge Weight Distribution Balance:
Application to Brain Networks.
AB - The aim of this study was to introduce a novel global measure of graph
complexity: Shannon graph complexity (SGC). This measure was specifically
developed for weighted graphs, but it can also be applied to binary graphs. The
proposed complexity measure was designed to capture the interplay between two
properties of a system: the 'information' (calculated by means of Shannon
entropy) and the 'order' of the system (estimated by means of a disequilibrium
measure). SGC is based on the concept that complex graphs should maintain an
equilibrium between the aforementioned two properties, which can be measured by
means of the edge weight distribution. In this study, SGC was assessed using four
synthetic graph datasets and a real dataset, formed by electroencephalographic
(EEG) recordings from controls and schizophrenia patients. SGC was compared with
graph density (GD), a classical measure used to evaluate graph complexity. Our
results showed that SGC is invariant with respect to GD and independent of node
degree distribution. Furthermore, its variation with graph size [Formula: see
text] is close to zero for [Formula: see text]. Results from the real dataset
showed an increment in the weight distribution balance during the cognitive
processing for both controls and schizophrenia patients, although these changes
are more relevant for controls. Our findings revealed that SGC does not need a
comparison with null-hypothesis networks constructed by a surrogate process. In
addition, SGC results on the real dataset suggest that schizophrenia is
associated with a deficit in the brain dynamic reorganization related to
secondary pathways of the brain network.
PMID- 28691562
TI - Mucoadhesive buccal tablets containing silymarin Eudragit-loaded nanoparticles:
formulation, characterisation and ex vivo permeation.
AB - Eudragit-loaded silymarin nanoparticles (SNPs) and their formulation into buccal
mucoadhesive tablets were investigated to improve the low bioavailability of
silymarin through buccal delivery. Characterisation of SNPs and silymarin buccal
tablets (SBTs) containing the optimised NPs were performed. Ex vivo permeability
of nominated SBTs were assessed using chicken pouch mucosa compared to SNPs and
drug suspension followed by histopathological examination. Selected SNPs had a
small size (<150 nm), encapsulation effciency (>77%) with drug release of about
90% after 6 h. For STBs, all physicochemical parameters were satisfactory for
different polymers used. DSC and FT-IR studies suggested the presence of
silymarin in an amorphous state. Ex vivo permeation significantly emphasised the
great enhancement of silymarin permeation after NPs formation and much more
increase after formulating into BTs relative to the corresponding drug dispersion
with confirmed membrane integrity. Incorporation of SNPs into BTs could be an
efficient vehicle for delivery of silymarin.
PMID- 28691563
TI - Information management for aged care provision in Australia: development of an
aged care minimum dataset and strategies to improve quality and continuity of
care.
AB - BACKGROUND: Efficient information systems support the provision of multi
disciplinary aged care and a variety of organisational purposes, including
quality, funding, communication and continuity of care. Agreed minimum data sets
enable accurate communication across multiple care settings. However, in aged
care multiple and poorly integrated data collection frameworks are commonly used
for client assessment, government reporting and funding purposes. OBJECTIVE: To
determine key information needs in aged care settings to improve information
quality, information transfer, safety, quality and continuity of care to meet the
complex needs of aged care clients. METHOD: Modified Delphi methods involving
five stages were employed by one aged care provider in Victoria, Australia, to
establish stakeholder consensus for a derived minimum data set and address
barriers to data quality. RESULTS: Eleven different aged care programs were
identified; with five related data dictionaries, three minimum data sets, five
program standards or quality frameworks. The remaining data collection frameworks
related to diseases classification, funding, service activity reporting, and
statistical standards and classifications. A total of 170 different data items
collected across seven internal information systems were consolidated to a
derived set of 60 core data items and aligned with nationally consistent data
collection frameworks. Barriers to data quality related to inconsistencies in
data items, staff knowledge, workflow, system access and configuration.
CONCLUSION: The development an internal aged care minimum data set highlighted
the critical role of primary data quality in the upstream and downstream use of
client information; and presents a platform to build national consistency across
the sector.
PMID- 28691564
TI - Concerns and hopes about outsourcing decisions regarding health information
management services at two teaching hospitals in Semnan, Iran.
AB - BACKGROUND: Changes in health programs in Iran have led to an increase in
administrative costs. One cost-saving option available to hospital administrators
is to outsource administrative services. OBJECTIVE: This study aimed to explore
the attitudes of hospital staff towards outsourcing health information management
services in advance of a decision being taken, to assist healthcare organisations
to assess the potential benefits and challenges of outsourcing such services.
METHOD: Six hundred and four clinical and allied health employees in two
hospitals in Iran, who had had prior experience with outsourcing hospital
services, responded to a survey designed to measure staff attitudes towards
outsourcing health information management services, based on their perceptions of
potential costs and benefits for the organisation and their own employment
prospects. A 16-item attitude scale, developed by the researchers, was used in
the study and demographic data were also collected. RESULTS: Summary statistics
showed that approximately one third of the sample (34.53%) had a negative view of
outsourcing, one third (35.16%) had a positive view, and 30.31% were neutral. An
exploratory factor analysis of items on the attitude scale identified three
underlying constructs, labelled: data security and management; workplace
environment; and staff and customer satisfaction. One item (concern about the
impact of outsourcing on staffing levels) did not load on any of the factors. A
separate analysis of this single item showed a significant relationship between
the sex of participants and their views on the impact of outsourcing on the
number of hospital staff employed (p<0.05). CONCLUSION: While results of this
study indicated that staff in hospitals surveyed held both positive and negative
views of outsourcing, a large number of staff in these hospitals (a third of the
total sample) had reservations about the skills of outside providers to securely
manage hospital data, and did not consider that outsourcing health information
management services would be positive for the organisation, their working
environment or for staff and patient satisfaction. These findings have important
implications for healthcare organisations planning to outsource health
information services. Further research that focuses on communication skills of
senior managers and their ability to provide team leadership is needed, as is
research into the impact of geographical location and current market forces that
impact on outsourcing tasks.
PMID- 28691565
TI - Type 1 diabetes self-management: developing a web-based telemedicine application.
AB - BACKGROUND: Self-management skills are essential for patients with diabetes
mellitus to minimise the risks of complications from their condition. The aim of
this research was to develop a web-based application for self-management of type
1 diabetes, suitable for use by patients, their carers and physicians. METHOD:
The study was comprised of two phases, the first being analysis of the kind of
information and capabilities required by potential users of the system. Based on
the results derived from the first phase of the study, the system prototype was
designed and then evaluated using the 'think aloud' method and a standard
questionnaire. The application was designed for use by patients, their carers and
physicians. Patients could enter the level of blood glucose, insulin and
activities on a daily basis, and physicians were able to supervise a patient's
health status from a distance. RESULTS: Users were generally satisfied with the
final version of the system. People with a wide range of literacy skills were
able to use the system effectively. CONCLUSION: Patients or their carers could
use the web-based application as a log book by entering the level of blood
glucose and insulin doses on a regular basis, and as an educational resource to
improve self-management skills. Physicians could use the system at any time
convenient to them to support patients by giving medical advice. Further research
is needed to report the effectiveness of the system in practice.
PMID- 28691566
TI - Improving data collection processes for routine evaluation of treatment cost
effectiveness.
AB - The healthcare system in Finland has begun routine collection of health-related
quality of life (HRQoL) information for patients in hospitals to support more
systematic cost-effectiveness analysis (CEA). This article describes the
systematic collection of HRQoL survey data, and addresses challenges in the
implementation of patient surveys and acquisition of cost data in the case
hospital. Challenges include problems with incomplete data and undefined
management processes. In order to support CEA of hospital treatments,
improvements are sought from the process management literature and in the
observation of healthcare professionals. The article has been written from an
information system and process management perspective, concluding that process
ownership, automation of data collection and better staff training are keys to
generating more reliable data.
PMID- 28691567
TI - Exploring the use of technology pathways to access health information by
Australian university students: a multi-dimensional approach.
AB - OBJECTIVE: Mobile wireless communication technologies (MWCT) and social media
(SM) networks create pathways for accessing widely available information that are
favoured particularly by younger generations. The purpose of this study was to
explore the way university students use these communication technologies to
access health information. METHOD: Participants ( n = 696), who were recruited
via an email invitation, completed an online self-reported survey that collected
multi-dimensional data consisting of quantitative, qualitative and spatial
statistics. RESULTS: The results indicate that technology was used extensively to
search for health information and resulted in positive changes in participants'
behaviours; however they perceived lack of reliability of the information as a
pressing issue. CONCLUSION: The results suggest that appealing, persuasive and
reliable MWCT and SM can be used extensively to promote health amongst Australian
youth.
PMID- 28691568
TI - Burden, pattern and causes of road traffic accidents in Bhutan, 2013-2014: a
police record review.
AB - Road traffic accidents (RTAs) are a major cause of death and injury globally.
There was little information on the burden and causes of RTAs in Bhutan. The
study estimates the burden and characteristics of RTAs and describes the victims
of RTAs in Bhutan. A descriptive cross-sectional study conducted analysing police
case records. In 2013-2014, 1866 accidents resulted in 1143 injuries and 157
deaths. We identified 39% more deaths from RTAs than that submitted to WHO in
2013 as the 30-day mortality. The main causes were careless driving and drunk
driving. Drivers and passengers constituted 86% of the deaths with few pedestrian
deaths. Data for in-hospital deaths or after discharge were not available.
Productivity loss due to RTA is around 1% of national GDP. There is significant
mortality and morbidity from RTAs in Bhutan. There is no coordinated system for
data collection and surveillance to monitor SDG goal 3.6.
PMID- 28691569
TI - Anatomical features of the cervical spinal canal in Chiari I deformity with
presyrinx: A case-control study.
AB - Purpose The relationship between syringomyelia and presyrinx, characterized by
edema in the spinal cord, has not been firmly established. Patients with
syringomyelia have abnormal spinal canal tapering that alters cerebrospinal fluid
flow dynamics, but taper ratios in presyrinx have never been reported. We tested
the hypothesis that presyrinx patients have abnormal spinal canal tapering.
Materials and methods At six medical institutions, investigators searched the
PACS system for patients with Chiari I and spinal cord edema unassociated with
tumor, trauma, or other evident cause. In each case taper ratios were calculated
for C1 to C4 and C4 to C7. In two age- and gender-matched control groups, Chiari
I patients with no syringomyelia and patients with normal MR scans, the same
measurements were made. Differences between groups were tested for statistical
significance with t tests. Results The study enrolled 21 presyrinx patients and
equal numbers of matched Chiari I and normal controls. C4 to C7 taper ratios were
positive and steeper in presyrinx patients than in the normal controls ( p =
0.04). The upper cervical spine, C1 to C4, tapered negatively in cases and
controls without significant differences between the groups. The difference in
degree of tonsillar herniation was statistically significant between presyrinx
patients and Chiari I controls ( p = 0.01). Conclusions Presyrinx patients have
greater than normal positive tapering in the lower cervical spine and greater
degree of tonsillar herniation than the controls.
PMID- 28691570
TI - Extra-axial cerebrospinal fluid spaces in children with benign external
hydrocephalus: A case-control study.
AB - Background The distinction between normal and pathological extra-axial
cerebrospinal fluid (CSF) spaces is unclear, with the use of the term benign
external hydrocephalus (BEH) not being well defined in clinical practice. This
study aimed to establish a distribution of metrics of the subarachnoid space in a
population of children diagnosed as normal, and investigate the clinical use of
the term BEH. Methods A retrospective case-control study on magnetic resonance
image scans was performed on 150 children diagnosed as normal and 10 children
diagnosed with BEH. Measurements were taken in the axial plane for CSF width
(CSFW), and interhemispheric width (IHW). Results Normal controls had a mean age
of 11.1 +/- 7.6 months (78 male, 72 female) and the BEH sample had a mean age of
10.6 +/- 7.8 months (six male, four female). Mean CSFW was 7.96 +/- 4.79 mm in
the BEH sample compared to 4.58 +/- 2.25 mm in the normal sample ( p < 0.05).
Mean IHW was 6.30 +/- 2.79 mm in the BEH sample compared to 3.89 +/- 1.83 mm in
the normal sample ( p < 0.05). However, a substantial overlap between the two
distributions of CSFW was found, with 50% of BEH patients lying within a single
standard deviation of the mean of normal individuals. Conclusion The absence of
diagnostic criteria for BEH means reporting is variable. Patients being diagnosed
with BEH who have no other clinical defects may represent the extreme of the
normal population rather than a distinct clinical entity.
PMID- 28691571
TI - Women's reasons for choosing abortion method: A systematic literature review.
AB - AIMS: We aim to describe and classify reasons behind women's choice between
medical and surgical abortion. METHODS: A systematic literature review was
conducted in PubMed and PsycINFO in October 2015. The subjects were women in
early pregnancy opting for abortion at clinics or hospitals in high-income
countries. We extracted women's reasons for choice of abortion method and
analysed these qualitatively, looking at main reasons for choosing either medical
or surgical abortion. RESULTS: Reasons for choice of method were classified to
five main groups: technical nature of the intervention, fear of complications,
fear of surgery or anaesthesia, timing and sedation. Reasons for selecting
medical abortion were often based on the perception of the method being 'more
natural' and the wish to have abortion in one's home in addition to fear of
complications. Women who opted for surgical abortion appreciated the quicker
process, viewed it as the safer option, and wished to avoid pain and excess
bleeding. Reasons were often based on emotional reactions, previous experiences
and a lack of knowledge about the procedures. Some topics such as pain or excess
bleeding received little attention. Overall the quality of the studies was low,
most studies were published more than 10 years ago, and the generalisability of
the findings was poor. CONCLUSION: Women did not base their choice of abortion
method only on rational information from professionals but also on emotions and
especially fears. Support techniques for a more informed choice are needed.
Recent high-quality studies in this area are lacking.
PMID- 28691572
TI - Using Systems Thinking to train future leaders in global health.
AB - Systems Thinking provides a useful set of concepts and tools that can be used to
train students to be effective and innovative global health leaders in an ever
changing and often chaotic world. This paper describes an experiential, multi
disciplinary curriculum that uses Systems Thinking to frame and analyse global
health policies and practices. The curriculum uses case studies and hands-on
activities to deepen students' understanding of the following concepts: complex
adaptive systems, dynamic complexity, inter-relationships, feedback loops, policy
resistance, mental models, boundary critique, leverage points, and multi
disciplinary, multi-sectoral, and multi-stakeholder thinking and action. A sample
of Systems Thinking tools for analysing global health policies and practices are
also introduced.
PMID- 28691573
TI - Plasticity in the Working Memory System: Life Span Changes and Response to
Injury.
AB - Working memory acts as a key bridge between perception, long-term memory, and
action. The brain regions, connections, and neurotransmitters that underlie
working memory undergo dramatic plastic changes during the life span, and in
response to injury. Early life reliance on deep gray matter structures fades
during adolescence as increasing reliance on prefrontal and parietal cortex
accompanies the development of executive aspects of working memory. The rise and
fall of working memory capacity and executive functions parallels the development
and loss of neurotransmitter function in frontal cortical areas. Of the affected
neurotransmitters, dopamine and acetylcholine modulate excitatory-inhibitory
circuits that underlie working memory, are important for plasticity in the
system, and are affected following preterm birth and adult brain injury.
Pharmacological interventions to promote recovery of working memory abilities
have had limited success, but hold promise if used in combination with behavioral
training and brain stimulation. The intense study of working memory in a range of
species, ages and following injuries has led to better understanding of the
intrinsic plasticity mechanisms in the working memory system. The challenge now
is to guide these mechanisms to better improve or restore working memory
function.
PMID- 28691574
TI - Enhancement of a prosthetic knee with a microprocessor-controlled gait phase
switch reduces falls and improves balance confidence and gait speed in community
ambulators with unilateral transfemoral amputation.
AB - BACKGROUND: Despite the evidence for improved safety and function of
microprocessor stance and swing-controlled prosthetic knees, non-microprocessor
controlled prosthetic knees are still standard of care for persons with
transfemoral amputations in most countries. Limited feature microprocessor
control enhancement of such knees could stand to significantly improve patient
outcomes. OBJECTIVES: To evaluate gait speed, balance, and fall reduction
benefits of the new 3E80 default stance hydraulic knee compared to standard non
microprocessor-controlled prosthetic knees. STUDY DESIGN: Comparative within
subject clinical study. METHODS: A total of 13 young, high-functioning community
ambulators with a transfemoral amputation underwent assessment of performance
based (e.g. 2-min walk test, timed ramp/stair tests) and self-reported (e.g.
falls, Activities-Specific Balance Confidence scale, Prosthesis Evaluation
Questionnaire question #1, Satisfaction with the Prosthesis) outcome measures for
their non-microprocessor-controlled prosthetic knees and again after 8 weeks of
accommodation to the 3E80 microprocessor-enhanced knee. RESULTS: Self-reported
falls significantly declined 77% ( p = .04), Activities-Specific Balance
Confidence scores improved 12 points ( p = .005), 2-min walk test walking
distance increased 20 m on level ( p = .01) and uneven ( p = .045) terrain, and
patient satisfaction significantly improved ( p < .01) when using the 3E80 knee.
Slope and stair ambulation performance did not differ between knee conditions.
CONCLUSION: The 3E80 knee reduced self-reported fall incidents and improved
balance confidence. Walking performance on both level and uneven terrains also
improved compared to non-microprocessor-controlled prosthetic knees. Subjects'
satisfaction was significantly higher than with their previous non-microprocessor
controlled prosthetic knees. The 3E80 may be considered a prosthetic option for
improving gait performance, balance confidence, and safety in highly active
amputees. Clinical relevance This study compared performance-based and self
reported outcome measures when using non-microprocessor and a new microprocessor
enhanced, default stance rotary hydraulic knee. The results inform rehabilitation
professionals about the functional benefits of a limited-feature, microprocessor
enhanced hydraulic prosthetic knee over standard non-microprocessor-controlled
prosthetic knees.
PMID- 28691575
TI - Performance, power and condom use: reconceptualised masculinities amongst Western
male sex tourists to Thailand.
AB - Each year large numbers of Western men travel to Thailand for sex tourism.
Although many will use condoms during their sexual encounters, others will not,
potentially exposing themselves to the risk of acquiring sexually transmitted
infections, including HIV. Although sex tourism in Thailand has been well
documented, the social drivers underpinning voluntary sexual risk-taking through
the avoidance of condoms remain poorly understood. Engaging with R.W. Connell's
concept of hegemonic masculinity and drawing on data collected from 1237 online
discussion board posts and 14 face-to-face interviews, this study considers the
ways in which understandings and performances of masculinities may inform the
sexual risk-taking behaviours of Western male sex tourists. It argues that for
some of these men, unprotected sex is viewed not as a reckless behaviour but,
instead, as a safe and appropriate masculine practice, supported by relationships
that are often framed as romantic and within a setting where HIV is still largely
considered a homosexual disease. With sex workers often disempowered to request
safer sexual practices, and some men's attitudes towards unprotected sex
resistant to external health promotion advice, the paper concludes by considering
what this might mean for policy and practice.
PMID- 28691576
TI - Time resolved computed tomography angiography in the evaluation of brain
arteriovenous malformation: a feasibility study.
AB - Background and purpose Digital subtraction angiography is the current gold
standard for diagnosing as well as the follow-up of cerebral arteriovenous
malformations. However, as it is invasive, relatively expensive and time
consuming, a non-invasive alternative is of interest. We aimed to evaluate the
feasibility of time resolved computed tomography angiography (TR-CTA) in a series
of five diagnosed cranial arteriovenous malformation patients, demonstrated by
conventional digital subtraction angiography with respect to acquisition,
depiction of angiographic phases and radiation exposure. Materials and methods
Five patients demonstrating a cranial arteriovenous malformation on digital
subtraction angiography were studied with TR-CTA. The TR-CTA imaging was done by
using a 128-detector computed tomography scanner. Digital subtraction angiography
and TR-CTA studies were independently read by two blinded observers, by using a
standardised scoring sheet. TR-CTA results were analysed with digital subtraction
angiography as the criterion standard. Results TR-CTA generated comparable
angiographic phases. In all five cases, there was complete agreement between
digital subtraction angiography and TR-CTA regarding the size, arterial feeders,
nidal morphology and venous drainage of the arteriovenous malformation.
Conclusions TR-CTA imaging as a technique is feasible, providing images with good
temporal and spatial resolution at an acceptable radiation dose. It appears to be
a promising non-invasive adjunct to digital subtraction angiography.
PMID- 28691577
TI - Test-potentiated learning: three independent replications, a disconfirmed
hypothesis, and an unexpected boundary condition.
AB - Arnold and McDermott [(2013). Test-potentiated learning: Distinguishing between
direct and indirect effects of testing. Journal of Experimental Psychology:
Learning, Memory, and Cognition, 39, 940-945] isolated the indirect effects of
testing and concluded that encoding is enhanced to a greater extent following
more versus fewer practice tests, referred to as test-potentiated learning. The
current research provided further evidence for test-potentiated learning and
evaluated the covert retrieval hypothesis as an alternative explanation for the
observed effect. Learners initially studied foreign language word pairs and then
completed either one or five practice tests before restudy occurred. Results of
greatest interest concern performance on test trials following restudy for items
that were not correctly recalled on the test trials that preceded restudy.
Results replicate Arnold and McDermott (2013) by demonstrating that more versus
fewer tests potentiate learning when trial time is limited. Results also provide
strong evidence against the covert retrieval hypothesis concerning why the effect
occurs (i.e., it does not reflect differential covert retrieval during pre
restudy trials). In addition, outcomes indicate that the magnitude of the test
potentiated learning effect decreases as trial length increases, revealing an
unexpected boundary condition to test-potentiated learning.
PMID- 28691578
TI - A hybrid clustering and classification approach for predicting crash injury
severity on rural roads.
AB - As a threat for transportation system, traffic crashes have a wide range of
social consequences for governments. Traffic crashes are increasing in developing
countries and Iran as a developing country is not immune from this risk. There
are several researches in the literature to predict traffic crash severity based
on artificial neural networks (ANNs), support vector machines and decision trees.
This paper attempts to investigate the crash injury severity of rural roads by
using a hybrid clustering and classification approach to compare the performance
of classification algorithms before and after applying the clustering. In this
paper, a novel rule-based genetic algorithm (GA) is proposed to predict crash
injury severity, which is evaluated by performance criteria in comparison with
classification algorithms like ANN. The results obtained from analysis of 13,673
crashes (5600 property damage, 778 fatal crashes, 4690 slight injuries and 2605
severe injuries) on rural roads in Tehran Province of Iran during 2011-2013
revealed that the proposed GA method outperforms other classification algorithms
based on classification metrics like precision (86%), recall (88%) and accuracy
(87%). Moreover, the proposed GA method has the highest level of interpretation,
is easy to understand and provides feedback to analysts.
PMID- 28691579
TI - Lipoxin A4 Suppresses Estrogen-Induced Epithelial-Mesenchymal Transition via ALXR
Dependent Manner in Endometriosis.
AB - OBJECTIVE: Epithelial-mesenchymal transition (EMT) is essential for
embryogenesis, fibrosis, and tumor metastasis. Aberrant EMT phenomenon has been
reported in endometriotic tissues of patients with endometriosis (EM). In this
study, we further investigated the molecular mechanism of which lipoxin A4 (LXA4)
suppresses estrogen (E2)-induced EMT in EM. STUDY DESIGN: The EMT markers were
analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) and
Western blot in eutopic endometrial epithelial cells (EECs) or investigated by
immunohistochemistry and qRT-PCR in endometriotic lesion of EM mice. The invasion
and migration under different treatments were assessed by transwell assays with
or without Matrigel. The messenger RNA (mRNA) and activities of matrix
metalloproteinase 2 (MMP-2) and MMP-9 were determined by qRT-PCR and gelatin
zymography, respectively. Luciferase reporter assay was used to measure the
activity of zinc finger E-box binding homeobox 1(ZEB1) promoter. The level of E2
in endometriotic tissues was assessed by enzyme-linked immunosorbent assay.
RESULTS: In eutopic EECs, stimulatory effects of E2 on EMT progress, migration,
and invasion were all diminished by LXA4. Lipoxin A4 reduced E2-induced ZEB1
promoter activity. Lipoxin A4 also attenuated the phosphorylation of
extracellular signal-regulated kinase and p38 mitogen-activated protein kinase
induced by E2. Co-incubation with Boc-2 rather than DMF antagonized the influence
of LXA4. Animal experiments showed that LXA4 inhibited the EMT progress, MMP
expression, and proteinase activities of endometriotic lesion in an LXA4 receptor
(ALXR) manner, which suppressed the progression of EM. ZEB1 mRNA expression was
upregulated and well correlated with E2 level in human endometrium. CONCLUSION:
Lipoxin A4 suppresses E2-induced EMT via ALXR-dependent manner in eutopic EECs,
which reveals a novel biological effect of LXA4 in EM.
PMID- 28691580
TI - Characterization of solid airborne particles deposited in snow in the vicinity of
urban fossil fuel thermal power plant (Western Siberia).
AB - Recognition and detailed characterization of solid particles emitted from thermal
power plants into the environment is highly important due to their potential
detrimental effects on human health. Snow cover is used for the identification of
anthropogenic emissions in the environment. However, little is known about types,
physical and chemical properties of solid airborne particles (SAP) deposited in
snow around thermal power plants. The purpose of this study is to quantify and
characterize in detail the traceable SAP deposited in snow near fossil fuel
thermal power plant in order to identify its emissions into the environment.
Applying the scanning electron microscopy-energy dispersive spectroscopy, and X
ray diffraction, mineral and anthropogenic phase groups in SAP deposited in snow
near the plant and in fly ash were observed. We identified quartz, albite and
mullite as most abundant mineral phases and carbonaceous matter, slag and
spherical particles as dominate anthropogenic phases. This is the first study
reporting that zircon and anthropogenic sulphide-bearing, metal oxide-bearing,
intermetallic compound-bearing and rare-earth element-bearing particles were
detected in snow deposits near thermal power plant. The identified mineral and
anthropogenic phases can be used as tracers for fossil fuel combustion emissions,
especially with regard to their possible effect on human health.
PMID- 28691581
TI - A shower before bedtime may improve the sleep onset latency of youth soccer
players.
AB - During the competitive season, soccer players are likely exposed to numerous
factors that may disrupt the process of sleep. The current investigation looked
to evaluate a practical sleep hygiene strategy (10-min showering at ~40 degrees C
before lights out), within a group of 11 youth soccer players in comparison to
normal sleeping conditions (control). Each condition consisted of three days
within a randomised crossover trial design. Sleep information was collected using
a commercial wireless bedside sleep monitor. Measures of skin temperature were
evaluated using iButton skin thermistors to establish both distal and proximal
skin temperatures and distal to proximal gradient. The shower intervention
elevated distal skin temperature by 1.1 degrees C (95% CI: 0.1-2.1 degrees C, p =
.04) on average prior to lights out. The elevation in distal temperature was also
present during the first 30-min following lights out (1.0 degrees C, 95% CI: 0.4
1.6 degrees C, p < .01). The distal to proximal gradient also showed a
significant effect between the conditions within the first 30-min after lights
out (0.7 degrees C, 95% CI: 0.3-1.2 degrees C, p < .01). On average the sleep
latency of the youth soccer players was -7-min lower (95% CI: -13 to -2 min, p <
.01) and sleep efficiency +2% higher (95% CI: 1-3%; p < .01) in the shower
condition. These findings demonstrate that a warm shower performed before lights
out may offer a practical strategy to promote thermoregulatory changes that may
advance sleep onset latency and improve sleep efficiency in athletes.
PMID- 28691582
TI - The Next Step in Understanding Impaired Reactive Balance Control in People With
Stroke: The Role of Defective Early Automatic Postural Responses.
AB - BACKGROUND AND OBJECTIVE: Postural muscle responses are often impaired after
stroke. We aimed to identify the contribution of deficits in very early postural
responses to poorer reactive balance capacity, with a particular focus on
reactive stepping as a key strategy for avoiding falls. METHODS: A total of 34
chronic stroke survivors and 17 controls were subjected to translational balance
perturbations in 4 directions. We identified the highest perturbation intensity
that could be recovered without stepping (single stepping threshold [SST]) and
with maximally 1 step (multiple stepping threshold [MST]). We determined onset
latencies and response amplitudes of 7 leg muscles bilaterally and identified
associations with balance capacity. RESULTS: People with stroke had a lower MST
than controls in all directions. Side steps resulted in a higher lateral MST than
crossover steps but were less common toward the paretic side. Postural responses
were delayed and smaller in amplitude on the paretic side only. We observed the
strongest associations between gluteus medius (GLUT) onset and amplitude and MST
toward the paretic side ( R2 = 0.33). Electromyographic variables were rather
weakly associated with forward and backward MSTs ( R2 = 0.10-0.22) and with SSTs
( R2 = 0.08-0.15). CONCLUSIONS: Delayed and reduced paretic postural responses
are associated with impaired reactive stepping after stroke. Particularly, fast
and vigorous activity of the GLUT is imperative for overcoming large sideways
perturbations, presumably because it facilitates the effective use of side steps.
Because people with stroke often fall toward the paretic side, this finding
indicates an important target for training.
PMID- 28691583
TI - Strategies used in improving and assessing the level of reporting of
implementation fidelity in randomised controlled trials of palliative care
complex interventions: A systematic review.
AB - BACKGROUND: Implementation fidelity is critical in evaluating effectiveness of
interventions. AIM: Identifying and summarising strategies to improve and assess
the level of reporting of implementation fidelity in randomised controlled trials
of palliative care complex interventions. DESIGN: Systematic review. DATA
SOURCES: Published and completed randomised controlled trials from 2000 to
current evaluating effectiveness of specialised palliative care services on
patient-centred outcomes in adult patients were examined. MEDLINE was searched
from 2008 to 29 September 2015 and supplemented by randomised controlled trials
identified in a 2008 systematic review. RESULTS: Altogether, 20 randomised
controlled trials involving 8426 patients were reviewed using 40 subcomponents of
five elements of implementation fidelity (resulting in 20 * 40 = 800 items). Over
88 strategies were identified, classified under the following elements:
'treatment design', 'training providers', 'delivery of treatment', 'receipt of
treatment' and 'enactment of treatment skills'. No single overarching strategy
was discovered. Strategies under 'treatment design' aimed to ensure equivalent
treatment dose between and within intervention and control groups, and delivery
of necessary ingredients. Ongoing 'training (of) providers' included supervision
and ensuring skill acquisition. Use of treatment manuals and implementation
checklists aimed to aid 'delivery of treatment'. Research teams aimed to improve
'receipt of treatment' by transmitting clear information and verifying
understanding, while improving 'enactment of treatment skills' by reviewing and
reinforcing prior content. Only 26% of the items received sufficient reporting;
34% were either not used or reported on. CONCLUSION: Implementation fidelity in
palliative care is under-recognised. A table to collate these strategies to
improve implementation fidelity in palliative care research and clinical practice
is proposed.
PMID- 28691584
TI - Fibrin gel as a scaffold for photoreceptor cells differentiation from conjunctiva
mesenchymal stem cells in retina tissue engineering.
AB - Stem cell-based therapies are attraction approaches for regenerative medicine for
treating retinal diseases. One of the limitations in cell therapy is cell death
following post-injection whit preventing functional integration with retinal
tissue. Fibrin gel, a bio-polymeric material with excellent biocompatibility,
provides numerous advantages as a tissue engineering scaffold and a stem cell
carrier. Therefore, current research is focusing on developing fibrin hydrogel
scaffolds to protect stem cells during delivery and to stimulate endogenous
regeneration through interactions of transplanted stem cells and retinal tissue.
In this study fibrin gel was used as hydrogel scaffold for immobilization of
cells. The structural characteristics of fibrin gel scaffold were examined with
SEM. Rheological properties of fibrin gel were measured by rheometer and
biodegradation rate of fibrin were assayed for 2 weeks. After isolation of stem
cells CJMSCs, the cells were differentiated into photoreceptor-like cells by
exposing with taurin for 14 days in tissue culture plate (TCP group) and fibrin
hydrogel (3 D group). The attachment of cells was analyzed with SEM and MTT. The
expression of rhodopsin, PKC, CRX, recoverin, peripherin, nestin and RPE65 as
photoreceptor-like cell markers was evaluated by immunocytochemistry and
quantitative real-time PCR (RT-PCR) in TCP and 3 D groups. The results of SEM
analysis showed CJMSCs were well attached in fibrin gels and there were good
integrity between cells and scaffold. The elastic modulus and constant
degradation of the gel contributes to the growth and proliferation of cells.
There was no toxicity effect of fibrin hydrogel on cells and the viability of
cultured cells was higher in 3 D fibrin gels in comparison with TCP groups. After
2 weeks, the expression of rhodopsin, PKC, CRX, peripherin, recoverin, nestin and
RPE65 as special markers of photoreceptor cells were detected by Real time PCR
and immunofluorescence that these expressions in 3 D groups were higher than TCP
groups. In conclusion, our findings showed that application of readily available
sources of adult stem cells like human conjunctiva stem cells encapsulated in
fibrin gel could be interesting strategy to enhance photoreceptor progenitor cell
numbers for repair and regeneration of retina disease such as photoreceptor
injury.
PMID- 28691585
TI - Hyper-brain connectivity in binge drinking college students: a diffusion tensor
imaging study.
AB - The current study used diffusion tensor imaging to examine patterns/degree of
brain connectivity in 12 college-aged binge drinking (BD) and 12 moderate
drinking individuals. Voxel-level and region-of-interest analyses revealed
increased connectivity of the BD brain in the right corona radiata, right
external capsule, and both the right and left cingulum. Also, fractional
anisotropy and axial diffusivity values of these regions correlated with a number
of drinking behaviors of the BD as well as both groups combined. It is
hypothesized that increased connectivity in the BD may produce difficulties with
regulatory control, contributing to their propensity to binge.
PMID- 28691586
TI - Low-cost Volumetric Ultrasound by Augmentation of 2D Systems: Design and
Prototype.
AB - Conventional two-dimensional (2D) ultrasound imaging is a powerful diagnostic
tool in the hands of an experienced user, yet 2D ultrasound remains clinically
underutilized and inherently incomplete, with output being very operator
dependent. Volumetric ultrasound systems can more fully capture a three
dimensional (3D) region of interest, but current 3D systems require specialized
transducers, are prohibitively expensive for many clinical departments, and do
not register image orientation with respect to the patient; these systems are
designed to provide improved workflow rather than operator independence. This
work investigates whether it is possible to add volumetric 3D imaging capability
to existing 2D ultrasound systems at minimal cost, providing a practical means of
reducing operator dependence in ultrasound. In this paper, we present a low-cost
method to make 2D ultrasound systems capable of quality volumetric image
acquisition: we present the general system design and image acquisition method,
including the use of a probe-mounted orientation sensor, a simple probe fixture
prototype, and an offline volume reconstruction technique. We demonstrate initial
results of the method, implemented using a Verasonics Vantage research scanner.
PMID- 28691587
TI - Improvement of amoxicillin removal from aqueous environment by applying
functionalized carbon nanotube.
AB - Multiwalled carbon nanotubes (MWCNTs) were applied for amoxicillin removal from
aqueous environment. To enhance the adsorption capacity of adsorbent, MWCNT with
modified surface was applied. A functional group as 8-hydroxyquinoline (8-HQ) and
carboxyl group were selected to modify the surface of MWCNT. Fourier transform
infrared spectroscopy and scanning electron microscopy confirmed the successful
surface modification of MWCNTs. Some important parameters associated with the
adsorption capacity such as pH, initial concentration of amoxicillin and
equilibrium time of adsorption were investigated for pristine and functionalized
MWCNTs. Adsorption results suggested that the maximsum removal efficiency of
pollutant was achieved at pH = 5 for pristine and 8-HQ functionalized carbon
nanotube (CNT) and pH = 3 for the functionalized CNT with carboxylic groups. The
equilibrium time of adsorption was 4 h for the pristine and 2 h for the
functionalized CNTs. The maximum adsorption capacity of 8-HQ CNTs was nearly 50%
higher than that of pristine MWCNT. The modeling of adsorption process suggested
that adsorption of amoxicillin on pristine and functionalized MWCNTs was best
fitted with Langmuir model. Moreover, pseudo-second-order kinetic model was found
to be the best kinetic model for the adsorption process. In conclusion,
functionalized MWCNT with 8-HQ functional groups offers a novel alternative for
removing amoxicillin from water.
PMID- 28691588
TI - The relation between the motor evoked potential and diffusion tensor tractography
for the corticospinal tract in chronic hemiparetic patients with cerebral
infarct.
AB - We examined the relation between the results of transcranial magnetic stimulation
(TMS) and diffusion tensor tractography (DTT) for the corticospinal tract (CST)
in chronic hemiparetic patients with a middle cerebral artery (MCA) territory
infarct. The amplitude of motor evoked potential (MEP) was closely related to the
FN of the CST on DTT in chronic hemiparetic patients with an MCA infarct. We
believe that our results would be helpful in more precise estimation of the CST.
PMID- 28691589
TI - Gender and atrial fibrillation: what role for real-world registry data?
PMID- 28691590
TI - Removal of diclofenac from water by in/out PAC/UF hybrid process.
AB - Results from a lab-scale investigation of a hybrid in/out ultrafiltration and
powdered activated carbon adsorption PAC/UF for removal of diclofenac (c0 = 5
mg/L) are presented. The efficiency of the process was compared for single pulse
and continuous carbon dosing (PAC dose 5 mg/L) in dechlorinated tap water under
fluxes of 87 and 135 L/(m2 h). For higher flux conditions, it was observed that
single pulse dosing has an advantage over continuous dosing procedure when
comparing cycle average removal efficiency. Increase of carbon dose under these
conditions increased cycle average removal only to a limited extent. PAC dose
above 15 mg/L did not give improvements of the removal. Hypothesis was made that
non-effective carbon distribution might be the possible reason.
PMID- 28691591
TI - Culture in la clinica: Evaluating the utility of the Cultural Formulation
Interview (CFI) in a Mexican outpatient setting.
AB - While the classification of psychiatric disorders has been critiqued for failing
to adequately account for culture, the inclusion of the Cultural Formulation
Interview (CFI) in the DSM-5 has been viewed as a promising development for the
inclusion of cultural factors in diagnosis and treatment of mental illness. In
this study, we assess the appropriateness, acceptability, and clinical utility of
the CFI among outpatients in a Mexican psychiatric hospital. Our assessment
included observations of psychiatric residents' application of the CFI with 19
patients during routine outpatient visits, along with pre- and post-CFI
interviews to determine providers' and patients' views of the CFI. The CFI was
generally well received by providers and patients, viewed as a way of building
trust and increasing providers' understanding of contextual factors influencing
mental illness, such as social support. However, the CFI questions specifically
related to "culture" were of limited effect and both patients and providers did
not view them as useful. We discuss implications for the clinical assessment of
cultural factors influencing mental health and illness and for the incorporation
of the CFI in Mexican clinical settings.
PMID- 28691592
TI - Reduction of Sleep Deprivation and Fatigue in Mass Transit Rail Operators.
AB - Sleep and work schedules differ considerably between rail workers and the broader
U.S. workforce. Due to extended work hours and night shift schedules, train and
engine service workers who operate passenger trains or move freight are most
vulnerable to fatigue. This article addresses the need for comprehensive fatigue
risk management systems (FRMS) for rail operators. Using a transactional
ergonomic perspective, FRMS are discussed with a focus on fatigue education and
administrative controls to reduce feelings of tiredness, low motivation, poor
concentration, and low physical activity among mass transit rail operators.
Recommendations for intervention implementation and evaluation are provided.
PMID- 28691593
TI - Electrographic Seizures in Preterm Neonates in the Neonatal Intensive Care Unit.
AB - OBJECTIVE: Characterize clinical and electroencephalography (EEG) characteristics
of preterm neonates undergoing continuous EEG in the neonatal intensive care
unit. METHODS: Retrospective study of preterm neonates born less than 37 weeks'
gestational age undergoing continuous EEG in the neonatal intensive care unit at
Boston Children's Hospital over a 2-year period. RESULTS: Fifty-two preterms (46%
male) had a mean gestational age of 32.8 weeks (standard deviation = 4.17).
Seizures were detected in 12/52 (23%), with EEG seizures detected in 4/12 (33%).
The median time from EEG to the first seizure was 0.5 hours (interquartile range
0.24-4). Factors associated with seizures were male gender (odds ratio = 4.65
[95% confidence interval = 1.02-21.24], P = .047) and lack of EEG state change
(odds ratio = 0.043 [95% confidence interval = 0.005-0.377], P = .04).
CONCLUSION: Twenty-three percent of preterms undergoing continuous EEG had EEG
seizures or electrographic seizures with no clear clinical correlate. This
confirms recent American Clinical Neurophysiology Society guidelines suggesting
that preterm neonates are at high risk for seizures.
PMID- 28691594
TI - An analytical hierarchy process-based study on the factors affecting legislation
on plastic bags in the USA.
AB - Annually, a large number of used plastic shopping bags are released into the
environment, posing significant threats to public health and wildlife. Owing to
these concerns, many local, regional, and national governments around the world
have passed legislation to ban or restrict the use of plastic shopping bags.
However, in the USA there are only 18 states that have approved plastic bag
bans/fees, and even within these states these regulations do not cover all cities
or counties. There are many factors that could affect the development and
implementation of these regulations. This article employs an analytical hierarchy
process to analyse the factors that could impact the enactment of plastic bag
regulations. Five impact factors are identified based on statistical data, that
is, geographical location, interest of industry achievable, cost of living, level
of economic development, and educational level of population. The weights of the
five impact factors are determined and it is found that the possibility of
banning or restricting plastic bags in general follows a certain pattern among
all states.
PMID- 28691595
TI - Application of hydrolases and probiotic Pediococcus acidilactici BaltBio01 strain
for cereal by-products conversion to bioproduct for food/feed.
AB - The aim of this study was to apply the enzymatic treatment and fermentation by
Pediococcus acidilactici BaltBio01 strain for industrial cereal by-products
conversion to food/feed bioproducts with high amount of probiotic lactic acid
bacteria (LAB). LAB propagated in potato media and spray-dried remained viable
during 12 months (7.0 log10 cfu/g) of storage and was used as a starter for
cereal by-products fermentation. The changes of microbial profile, biogenic
amines (BAs), mycotoxins, lactic acid (L+/D-), lignans and alkylresorcinols (ARs)
contents in fermented cereal by-product were analysed. Cereal by-products
enzymatic hydrolysis before fermentation allows to obtain a higher count of LAB
during fermentation. Fermentation with P. acidilactici reduce mycotoxins content
in fermented cereal by-products. According to our results, P. acidilactici
multiplied in potato juice could be used for cereal by-products fermentation, as
a potential source to produce safer food/feed bioproduct with high amount of
probiotic LAB for industrial production.
PMID- 28691596
TI - The relationship between the INTERMED patient complexity instrument and Level of
Care Utilisation System (LOCUS).
AB - OBJECTIVE: To investigate the concurrent and criterion validity of two
independently developed measurement instruments, INTERMED and LOCUS, designed to
improve the treatment and clinical management of patients with complex symptom
manifestations. METHODS: Participants (N = 66) were selected from hospital
records based on the complexity of presenting symptoms, with tripartite diagnoses
across biological, psychiatric and addiction domains. Biopsychosocial information
from hospital records were submitted to INTERMED and LOCUS grids. In addition,
Global Assessment of Functioning (GAF) ratings were gathered for statistical
analyses. RESULTS: The product moment correlation between INTERMED and LOCUS was
0.609 (p = .01). Inverse zero-order correlations for INTERMED and LOCUS total
score and GAF were obtained. However, only the beta weight for LOCUS and GAF was
significant. An exploratory principal components analysis further illuminated
areas of convergence between the instruments. CONCLUSIONS: INTERMED and LOCUS
demonstrated shared variance. INTERMED appeared more sensitive to complex medical
conditions and severe physiological reactions, whereas LOCUS findings are more
strongly related to psychiatric symptoms. Implications are discussed.
PMID- 28691597
TI - Clinical factors associated with positive capsule endoscopy findings in patients
with obscure gastrointestinal bleeding: a single-center study.
AB - BACKGROUND: Capsule endoscopy (CE) is a useful tool for patients with obscure
gastrointestinal bleeding (OGIB), but positive finding rate differs among trials,
which may be attributable to the difference in patients' background. OBJECTIVES:
To evaluate the predictive factors associated with positive findings on CE.
METHODS: Consecutive patients with OGIB who underwent CE between March 2004 and
May 2015 at a single university hospital were enrolled. Patients' clinical
factors and CE data were reviewed retrospectively, and we evaluated the
relationship between clinical factors and positive findings by univariate and
multivariate logistic regression analyses. RESULTS: Five hundred and seventy
eight patients were included in the analysis. Positive CE findings were obtained
in 284 patients (49.1%). In multivariate analysis, low hemoglobin level (odds
ratio (OR), 1.142 per 1 g/dL decrease; p < .001), Charlson comorbidity index
(CCI) score (OR, 1.170 per 1 point increase; p = .002), and non-steroidal anti
inflammatory drug (NSAID) use (OR, 1.640; p = .044) were associated with an
increased prevalence of positive findings. As for components of CCI, malignant
tumor (OR, 1.839; p = .017) was associated with the positive findings.
CONCLUSIONS: OGIB patient with a low-hemoglobin level, complex and severe
comorbidities, and NSAID use should receive CE.
PMID- 28691598
TI - Decrease in musculoskeletal pain after 4 and 12 months of an aerobic exercise
intervention: a worksite RCT among cleaners.
AB - BACKGROUND: Prevalence of musculoskeletal pain is high in jobs with high physical
work demands. An aerobic exercise intervention targeting cardiovascular health
was evaluated for its long term side effects on musculoskeletal pain. OBJECTIVE:
The objective was to investigate if aerobic exercise affects level of
musculoskeletal pain from baseline to 4- and 12-months follow-up. METHODS: One
hundred-and-sixteen cleaners aged 18-65 years were cluster-randomized. The
aerobic exercise group ( n = 57) received worksite aerobic exercise (30 min twice
a week) and the reference group ( n = 59) lectures in health promotion. Strata
were formed according to closest manager (total 11 strata); clusters were set
within strata (total 40 clusters, 20 in each group). Musculoskeletal pain data
from eight body regions was collected at baseline and after 4- and 12-months
follow-up. The participants stated highest pain in the last month on a scale from
0, stating no pain, up to 10, stating worst possible pain. A repeated-measure 2 *
2 multi-adjusted mixed-models design was applied to compare the between-groups
differences in an intention to treat analysis. Participants were entered as a
random effect nested in clusters to account for the cluster-based randomization.
RESULTS: Clinically significant reductions (>30%, f 2 > 0.25) in the aerobic
exercise group, compared to the reference group, in pain intensity in neck,
shoulders, arms/wrists were found at 12-months follow-up, and a tendency ( p =
0.07, f 2 = 0.18) to an increase for the knees. At 4-months follow-up the only
significant between-group change was an increase in hip pain. CONCLUSIONS: This
study indicates that aerobic exercise reduces musculoskeletal pain in the upper
extremities, but as an unintended side effect may increase pain in the lower
extremities. Aerobic exercise interventions among workers standing or walking in
the majority of the working hours should tailor exercise to only maintain the
positive effect on musculoskeletal pain.
PMID- 28691599
TI - Sheep model of haemodialysis treatment.
AB - More than two million patients received haemodialysis (HD) in 2013. Many methods
for improving dialysis therapy outcomes have been tested. Nevertheless, patients
continue to experience high morbidity and mortality rates. We aimed to develop an
animal model of HD treatment to study methods that would prevent the adverse
effects of renal replacement therapy. The study was conducted using six male
Merino sheep. The animals underwent a two-step bilateral nephrectomy, and a
permanent dual-lumen catheter was inserted into the jugular vein. In each animal,
10 short, daily HD treatments were conducted. The dialysis prescription was
adjusted individually to each animal. Measures of dialysis adequacy (spKt/V and
urea reduction ratio [URR]) were calculated for each HD treatment. All animals
remained in a good clinical state during the experiment. However, a sustained
decrease in red blood cell count was detected. The average URR was 0.65 +/- 0.01,
whereas the calculated spKt/V was approximately 1.16 +/- 0.03. Neither
hyperphosphataemia nor a significant decline in serum albumin concentrations were
detected during the study. A sustained increase in serum potassium concentrations
was detected on consecutive days of the experiment. All sheep survived the
treatment and were euthanized at the end of the experiment. In conclusion, we
developed a reproducible sheep model of HD treatment. The gentle nature and
specific anatomical features of sheep provided easy blood access and allowed us
to perform HD without pharmacological intervention. However, some differences in
sheep physiology relative to human physiology must be considered when
interpreting the results of the study.
PMID- 28691600
TI - Simultaneous detection of multiple pathogens by multiplex PCR coupled with DNA
biochip hybridization.
AB - Traditional serological enzyme-linked immunosorbent assay (ELISA) is routinely
used to monitor pathogens during quarantine in most animal facilities to prevent
possible infection. However, the ELISA platform is a single-target assay, and
screening all targeted pathogens is time-consuming and laborious. In this study,
to increase sensitivity and to reduce diagnosis time for high-throughput
processes, multiplex PCR and DNA biochip techniques were combined to develop a
multi-pathogen diagnostic method for use instead of routine ELISA. Eight primer
sets were designed for multiplex PCR to detect genes from seven targeted
bacterial and viral pathogens. DNA-DNA hybridization was conducted on a biochip
following the multiple PCR analysis. Using this method, a total of 24 clinical
samples were tested, and the result showed that not only single infection but
also co-infection by multi-pathogens can be detected. In conclusion, multiplex
PCR coupled with a DNA biochip is an efficient method for detecting multi
pathogens in a reaction. This platform is a useful tool for quarantine services
and disease prevention in animal facilities.
PMID- 28691601
TI - Task-Specific and Functional Effects of Speed-Focused Elliptical or Motor
Assisted Cycle Training in Children With Bilateral Cerebral Palsy: Randomized
Clinical Trial.
AB - BACKGROUND: Locomotor training using treadmills or robotic devices is commonly
utilized to improve gait in cerebral palsy (CP); however, effects are
inconsistent and fail to exceed those of equally intense alternatives. Possible
limitations of existing devices include fixed nonvariable rhythm and too much
limb or body weight assistance. OBJECTIVE: To quantify and compare effectiveness
of a motor-assisted cycle and a novel alternative, an elliptical, in CP to
improve interlimb reciprocal coordination through intensive speed-focused leg
training. METHODS: A total of 27 children with bilateral CP, 5 to 17 years old,
were randomized to 12 weeks of 20 minutes, 5 days per week home-based training
(elliptical = 14; cycle = 13) at a minimum of 40 revolutions per minute, with
resistance added when speed target was achieved. Primary outcomes were self
selected and fastest voluntary cadence on the devices and gait speed. Secondary
outcomes included knee muscle strength, and selective control and functional
mobility measures. RESULTS: Cadence on trained but not nontrained devices
increased, demonstrating task specificity of training and increased exercise
capability. Mean gait speed did not increase in either group, nor did parent
reported functional mobility. Knee extensor strength increased in both. An
interaction between group and time was seen in selective control with scores
slightly increasing for the elliptical and decreasing for the cycle, possibly
related to tighter limb coupling with cycling. CONCLUSIONS: Task-specific effects
were similarly positive across groups, but no transfer was seen to gait or
function. Training dose was low (<=20 hours) compared with intensive upper-limb
training recommendations and may be insufficient to produce appreciable clinical
change.
PMID- 28691602
TI - Somatosensory Feedback to the Cheek During Virtual Visual Feedback Therapy
Enhances Pain Alleviation for Phantom Arms.
AB - BACKGROUND: Patients who suffer from phantom limb pain can perceive tactile
stimuli applied to the cheek on their affected side as if it were coming from
their phantom limb, a phenomenon called "referred sensation." OBJECTIVES: To
investigate the analgesic effect produced by tactile feedback provided to the
cheek during neurorehabilitation using visual feedback. METHODS: Nine
participants with phantom upper limb pain performed virtual reality
neurorehabilitation exercises in which they repeatedly touched a target object
with a virtual representation of their affected limb. We applied tactile feedback
to their cheek when their virtual affected limb touched a virtual object (Cheek
Condition). We also included 2 control conditions where tactile feedback was
either applied to their intact hand (Intact Hand Condition) or not applied at all
(No Stimulus Condition). We evaluated pain intensity on an 11-point rating scale
and pain quality using the short-form McGill Pain Questionnaire before and after
each rehabilitation condition. RESULTS: The median pain-reduction rate in the
Cheek Condition (33.3 +/- 24.4%) was significantly higher than in the Intact Hand
Condition (16.7 +/- 12.3%) and the No Stimulus Condition (12.5 +/- 13.5%; P <
.05). Even patients who did not feel referred sensations reported significant
pain reduction after the Cheek Condition. CONCLUSIONS: The analgesic effect of
neurorehabilitative visual feedback during phantom limb movement is significantly
improved by applying somatosensory feedback to the cheek on the affected side.
Further studies are needed to extend these findings to objective pain measures
and to elucidate the neural mechanisms that underlie the analgesic effect.
PMID- 28691603
TI - Dichorionic Twins Discordant for Massive Perivillous Fibrinoid Deposition: Report
of a Case and Review of the Literature.
AB - Massive perivillous fibrinoid deposition (MFD) and maternal floor infarction
(MFI) are lesions of unknown etiology associated with poor perinatal outcomes,
including fetal intrauterine growth restriction and neurodevelopmental injury,
high risks of pregnancy loss, and recurrence in subsequent gestations. MFI
comprises massive intervillous fibrinoid deposition concentrated at the maternal
floor. MFD is a similar lesion but is diffuse within the parenchyma. MFD/MFI
lesions represent a spectrum of severity of cloak-like perivillous fibrinoid
deposition, and there is mounting evidence that, often, they represent sequelae
of immune-mediated phenomena and/or an imbalance in factors that normally
maintain the fluidity of blood in the maternal space. There are only a handful of
reported instances of discordant MFD/MFI occurrence in twin placentas. We present
a fourth such occurrence in a fused, dichorionic diamniotic twin placenta and
submit that our dizygotic twin gestation case provides additional supportive
evidence that immune-mediated mechanisms are involved in the formation of
pathological accumulations of fibrinoid, at least in some cases.
PMID- 28691604
TI - Parent Psychopathology and Neurocognitive Functioning in Children With ADHD.
AB - OBJECTIVE: The objective of this study was to examine the association between
parent mental health (ADHD and depression) and offspring performance on
neurocognitive tasks in children with ADHD. METHOD: The clinical sample consisted
of 570 children (85% males, mean age: 10.77 years) with ADHD who completed
neurocognitive tasks measuring working memory, attention set-shifting, and
motivational deficits. Questionnaire measures were used to assess ADHD and
depression symptom presence in parents. RESULTS: Controlling for ADHD severity,
children of parents with ADHD had poorer working memory ( B = -0.25, 95%
confidence interval [CI] [-0.45, -0.07], p = .01) and increased errors on the
extra dimensional shift stage of the set-shifting task ( B = 0.26 95% CI [0.02,
0.50], p = .04). Parent depression was not associated with offspring performance
on any of the assessed neurocognitive tasks. CONCLUSION: Children with ADHD who
have a parent with ADHD symptom presence are a subgroup of children who may have
additional neurocognitive impairments that have potential implications when
implementing interventions that target cognition and learning.
PMID- 28691605
TI - Effects of lesions to the left lateral prefrontal cortex on task-specific top
down biases and response strategies in blocked-cyclic naming.
AB - Anders, Ries, van Maanen and Alario put forward evidence accumulation modelling
of object naming times as an alternative to neural network models of lexical
retrieval. The authors exemplify their approach using data from the blocked
cyclic naming paradigm, requiring speakers to repeatedly name small sets of
related or unrelated objects. The effects observed with this paradigm are
understood reasonably well within the tradition of neural network modelling.
However, implemented neural network models do not specify interfaces for task
specific top-down influences and response strategies that are likely to play a
role in the blocked-cyclic naming paradigm, distinguishing it from continuous,
non-cyclic manipulations of the naming context. I argue that the evidence
accumulation approach falls short on this account as well, as it does not specify
the potential contribution of task-specific top-down processes and strategic
facilitation effects to the response time distributions. Future endeavours to
model or fit data from blocked-cyclic naming experiments should strive to do so
by simultaneously considering data from continuous context manipulations.
PMID- 28691606
TI - Word selection deficits and multiword speech.
AB - Through computational modelling of language behaviour in both healthy and brain
damaged individuals, Anders, Ries, van Maanen and Alario ( in press ) propose
that to facilitate word selection when alternatives compete for production, the
left lateral prefrontal cortex (PFC) changes the threshold for word selection.
Because selecting a word during multiword speech involves resolving competition
from target-related competitors as well as words produced in the past and future,
a word-selection deficit caused by damage to the left PFC may result in
difficulties in producing multiword speech. I review evidence in support of this
hypothesis and discuss alternative explanations. Future work should extend Anders
and colleagues' conclusions to understand whether a deficit in word selection
when producing single words accounts for failures to communicate via multiword
speech.
PMID- 28691607
TI - A blind spot in correct naming latency analyses.
AB - Speech errors and naming latencies provide two complementary sets of behavioural
data for understanding language production processes. A recent analytical trend
applied to intact and impaired production alike-highlights a link between
specific features of correct picture naming latency distributions and the
retrieval processes thought to underlie them. Although chronometric approaches to
language production typically consider correct response times in isolation,
adequately accounting for their distributions in error-prone situations requires
also considering the errors that sometimes censor them. In this paper, I
illustrate by simulation how excluding incorrect word retrievals predictably
alters observed distributions of correct naming latencies. To the extent that
naming errors impose a stochastic deadline on successful production, their
censoring should tend to reduce the mean, variance, and skew of observed
latencies for correct responses, relative to the uncensored underlying
distribution.
PMID- 28691609
TI - Kangaroo care for low birthweight infants.
AB - Background Kangaroo mother care (KMC) is defined by the World Health Organization
(WHO) as early, continuous and prolonged kin-to-skin contact between mother and
baby.
PMID- 28691611
TI - Monkey mascot used to gather children's opinions.
AB - The use of a monkey mascot has been piloted at Lincoln County Hospital to gather
feedback on healthcare services and experiences from young patients.
PMID- 28691610
TI - Evidence suggests that kangaroo mother care improves premature infant outcomes.
AB - The British Association of Perinatal Medicine ( 2016 ) has reported that 60,000
70,000 infants a year require neonatal intervention in the UK, or about 10% of
all babies born in England. The World Health Organization ( 2015 ) found a 0%
decrease in mortality rates in neonatal units worldwide through the adoption of
KMC.
PMID- 28691612
TI - NSPCC helpline reports 200% increase in calls.
AB - An NSPCC report highlights a 200% increase in calls to the charity's helpline
about emotional abuse of children.
PMID- 28691613
TI - Children can thrive on a blended diet.
AB - Using a blended diet to feed a child through gastrostomy is still a controversial
practice, but the pioneering leadership of nurse consultant Sian Thomas could
change this. After being approached by the parent of a child with complex needs,
Ms Thomas developed a multi-agency protocol to help her attend a mainstream
school.
PMID- 28691615
TI - Teachers to get specialist training.
AB - Teachers who have had special training to deal with pupils' mental health
problems will make a 'real difference to children's lives', the prime minister
has said.
PMID- 28691616
TI - Assessment of Northern Jordanian adolescents' knowledge and attitudes towards
asthma.
AB - Background Asthma is a chronic illness of the airways that can cause a persistent
cough. The illness affects a significant population of young people worldwide and
can affect their ongoing quality of life. Aim To explore Jordanian adolescents'
knowledge and attitudes to asthma. Method A cross-sectional research design was
used with a convenience sample of 302 adolescents from six schools in northern
Jordan, who completed a self-reported knowledge and attitude survey. Results
Although the adolescents had an adequate knowledge level about asthma, several
areas of knowledge deficit were identified and some negative attitudes were
demonstrated. No significant association was found between adolescents' level of
knowledge and their attitudes to adolescents with asthma. Conclusion Jordanian
adolescents need more educational programmes about living with life-changing
chronic illnesses such as asthma, and about how the knowledge and positive
attitudes of peer groups can normalise the illness for the affected person,
enhancing their quality of life.
PMID- 28691617
TI - Improving outcomes through training staff in neurological assessment.
AB - Aim The aim of this project is to provide staff with appropriate training and
support to ensure that nurses offer up-to-date, evidenced-based, neurological
care, and that the best clinical outcomes are achieved.
PMID- 28691618
TI - Improvements needed in mental health care for young people.
AB - A study of child and adolescent mental health services (CAMHS) in all 28
countries of the EU, including legal aspects of adolescent care, has found
provision needs to be improved.
PMID- 28691619
TI - Social stigma stops adolescents from using inhalers for asthma.
AB - Forgetfulness, poor routines, inadequate inhaler technique, organisational
difficulties and families not understanding or accepting their children's asthma
are described as barriers to the use of inhalers among adolescents with asthma.
PMID- 28691621
TI - Klinefelter syndrome.
AB - Klinefelter syndrome, affecting males, is a collection of characteristics that
occurs as a result of two or more X chromosomes. The syndrome was named after
Harry Klinefelter, an American endocrinologist, and is common - occurring in all
races. It is thought that one male in every 500 live births is affected and the
incidence is rising. However, this may be due to increasing awareness, reflective
of the sophistication of the methods to diagnose.
PMID- 28691622
TI - Risk factors for childhood obesity: a data analysis of the Welsh Health Survey.
AB - Background The prevalence of childhood obesity in Wales is 12%. It has been
estimated that obesity will cost the NHS L10 billion a year by 2050 ( Government
Office for Science 2007 ). Aim To determine important risk factors associated
with childhood obesity from the data in the Welsh Health Survey 2008 to 2012.
Method The analysis used survey data from 11,279 children aged 4-15 years. The
lifestyle variables considered as potential risk factors for obesity included:
intake of sugar-sweetened drinks; unhealthy food consumption; physical activity;
and currently-treated illnesses. The sociodemographic and socioeconomic factors
included: sex; age; Welsh Index of Multiple Deprivation quintile; National
Statistics Socio-economic Classification; and housing tenure. Results A total of
1,582 (20%) children were obese. A significant association was found between
obesity and having one illness - odds ratio (OR) 1.20 (95% confidence interval
(CI): 1.05 to 1.38, P=0.008) and having two or more illnesses - OR 1.50 (95% CI:
1.22 to 1.85, P<0.001), and not meeting the physical activity recommendation - OR
1.33 (95% CI: 1.17 to 1.52, P<0.001). Conclusion Every child should meet the
physical activity recommendation and those with an illness should receive a care
plan to prevent or manage obesity, although this is difficult in the time
available for children in clinics and consultations.
PMID- 28691623
TI - Roald Dahl charity funds network of specialist nurses.
AB - As the author of some of the most famous children's books, Roald Dahl's impact on
the lives of young people is obvious. But less well known is his legacy in terms
of helping the sick and injured.
PMID- 28691625
TI - Health visitors vital to child development.
AB - The RCN says that health visiting must be a top government priority if children
are to flourish.
PMID- 28691624
TI - Hospitals test if therapy dogs can aid children's recovery.
AB - Children undergoing hospital treatment are being supported by therapy dogs in a
new study to establish if the pets are beneficial to their recovery.
PMID- 28691626
TI - Reflective learning.
AB - Good care matters. If I learned one thing from my nursing elective in Malawi,
East Africa, it was this: whatever the environment or situation, good care should
be at the heart of our practice.
PMID- 28691629
TI - Nursing secondments are good investments.
AB - Nurse recruitment and retention is at an all-time low, with nurse numbers
expected to decrease as many nurses near retirement age and fewer people apply
for nursing degree courses. One in nine nursing posts in England, is currently
unfilled.
PMID- 28691627
TI - A glimpse of nursing student life in China.
AB - When Toni Bewley first arrived at Harbin University in Daqing, north-eastern
China, she was intrigued to discover that students do not undertake any clinical
placements during their three-year degree courses.
PMID- 28691632
TI - Response to attack made me proud to be a nurse.
AB - Working as a paediatric nurse at the Royal Manchester Children's Hospital for the
past five years, I have often been exposed to difficult situations and worked in
challenging circumstances. Life as a nurse on the ward can be difficult on an
emotional level.
PMID- 28691633
TI - Childhood stroke.
AB - Essential facts [Figure: see text] Around 400 children in the UK have a stroke
each year, leaving many with severe physical and mental impairments. Many
professionals and parents can mistakenly think that strokes only affect older
people, leading to delays in diagnosis and prompt treatment. Children may need
long-term support including physiotherapy, speech and language therapy and
support with education.
PMID- 28691634
TI - Understanding the nurse's role in identifying children with intellectual
disability.
AB - The early diagnosis of children who have intellectual disability (ID) is crucial
to ensuring the varied and complex needs of these people and their families are
met in a timely and appropriate way. The ability to easily identify all children
who should be assessed for ID would increase the chances of children with ID
being diagnosed early on in life. This article describes ID, the kind of support
children with ID need, and how nursing staff might use the Child and Adolescent
Intellectual Disability Screening Questionnaire (CAIDS-Q) to help identify
children who should be formally assessed for ID. Nurses who would benefit from a
greater ability to identify ID include health visitors, school nurses, practice
nurses, and nurses working in paediatric clinics.
PMID- 28691635
TI - Multi-agency practice for developing a blended diet for children fed via
gastrostomy.
AB - The administration of a blended diet via a gastrostomy tube to children with
complex needs is an evolving area of practice. Healthcare professionals must
provide guidance, promote best practice and optimise patient safety where
patients and families choose a blended diet in preference to the prescribed
commercial feed. The Aneurin Bevan Health University Health Board in Newport,
Wales, took a collaborative approach, by working with parents as equal partners,
to enable a child with complex needs to receive a blended diet at school. The
development of a protocol and risk-assessed approach enabled the delivery of
bespoke flexible care that met the holistic needs of the child and family and
improved the child's quality of life. The initiative also led to positive
outcomes for the school and wider community.
PMID- 28691636
TI - Optimal control of greenhouse gas emissions and system cost for integrated
municipal solid waste management with considering a hierarchical structure.
AB - This study presents a synergic optimization of control for greenhouse gas (GHG)
emissions and system cost in integrated municipal solid waste (MSW) management on
a basis of bi-level programming. The bi-level programming is formulated by
integrating minimizations of GHG emissions at the leader level and system cost at
the follower level into a general MSW framework. Different from traditional
single- or multi-objective approaches, the proposed bi-level programming is
capable of not only addressing the tradeoffs but also dealing with the leader
follower relationship between different decision makers, who have dissimilar
perspectives interests. GHG emission control is placed at the leader level could
emphasize the significant environmental concern in MSW management. A bi-level
decision-making process based on satisfactory degree is then suitable for solving
highly nonlinear problems with computationally effectiveness. The capabilities
and effectiveness of the proposed bi-level programming are illustrated by an
application of a MSW management problem in Canada. Results show that the obtained
optimal management strategy can bring considerable revenues, approximately from
76 to 97 million dollars. Considering control of GHG emissions, it would give
priority to the development of the recycling facility throughout the whole
period, especially in latter periods. In terms of capacity, the existing landfill
is enough in the future 30 years without development of new landfills, while
expansion to the composting and recycling facilities should be paid more
attention.
PMID- 28691637
TI - Sociodemographic correlates of physical activity and screen time among
adolescents in Canada and Guatemala: Results from the COMPASS system.
AB - This study was to compare the levels of physical activity (PA) and sedentary
behavior (SB) between Canadian and Guatemalan adolescents, and to examine
associations of sociodemographic variables with PA and screen time among
adolescents in Canada and Guatemala. Self-reported, cross-sectional data from
students in grades 9-12 who participated in the 2015 COMPASS study (Canada; n =
39,817; mean age = 15.6 years) and COMPASS-Guatemala ( n = 1,221; mean age = 15.1
years) were used. Sociodemographic variables included age, gender, ethnicity
(exclusively among Canadians), and weekly money allowance. Outcome variables
included meeting the PA guidelines (?60 minutes/day) and the screen time
recommendations within the SB guidelines (<2 hours/day), and participation in
organized sports in and out of school. Chi-squared tests and linear and logistic
regressions were used to test the study objectives. The proportions of
participants meeting the PA guidelines were 48.7% and 41.3% for Canadians and
Guatemalans, respectively. More Guatemalan adolescents than Canadians met the
screen time recommendations (24.9% vs. 16.5%). Older age, being male, being non
White, and $0-$5/unknown of allowance were associated with meeting the PA
guidelines among Canadians. Gender (being male) was the only variable associated
with meeting the PA guidelines among Guatemalan adolescents. Older age, being
male, being non-White, and $0-$5/unknown of allowance were associated with
organized sport participation among Canadians. Among Guatemalans, being aged 15
16 years and having 0-35 quetzals/unknown of allowance were associated with
participating in competitive school sports. Being male was associated with
participating in recreational school sports or league/team sports outside of
school. Older age, being female, being non-White, and ?$6 of allowance were
associated with meeting the screen time recommendations among Canadians. Older
age and having ?150 quetzals of allowance were associated with meeting the screen
time recommendations among Guatemalan adolescents. These findings can inform
researchers and policy makers when developing country-specific targeted
interventions and programs that promote physically active lifestyles.
PMID- 28691638
TI - Maternal late pregnancy anxiety and stress is associated with children's health:
a longitudinal study.
AB - AIM: Maternal prenatal anxiety and stress (PNS) have been positively associated
to physical health prob lems in offspring in the first year of life. Whether
these associations are transient, persistent, or even progressive over time, is
as yet unknown. The goal of this study is to investigate associations between
late pregnancy PNS and child health from 18 months to age 6. METHODS: Mothers
were recruited in late pregnancy, and had uncomplicated, singleton pregnancies
without physical health problems. Around week 37 of pregnancy, mothers reported
on their PNS by means of questionnaires, and provided saliva for determination of
circadian cortisol concentrations. Children's illnesses in the preceding year
were assessed using maternal reports at 30, 48, 60, and 72 months. Antibiotic use
was obtained from medical records between one and six years. Multilevel models
(N1/4174) showed a positive relation between maternal prenatal general and
pregnancy-specific anxiety during late pregnancy and offspring respiratory
illnesses and symptoms. Interaction effects with time indicated that more PNS was
related to more respiratory illnesses until toddlerhood, but not later in life.
Furthermore, maternal prenatal cortisol concentrations were related to child
digestive illnesses. A steeper maternal cortisol decline over the day was related
to more child digestive illnesses, until around three years of age. Finally,
children of mothers who suffered more from daily hassles during pregnancy
received more antibiotics between one and six years of age. PNS was not related
to general and skin illnesses. CONCLUSION: Summarizing, this study showed that
late pregnancy anxiety and cortisol was associated with children's respiratory
and digestive illnesses till the age of 3.0-3.5 years. Additionally, more daily
hassles were related to more prescribed antibiotics between one and six years.
These findings point in the direction of possible effects of PNS persisting
beyond the first year of life and into toddlerhood, but disappearing at older
ages.
PMID- 28691639
TI - Energy saving control strategies for Haliscomenobacter hydrossis filamentous
sludge bulking in the A/O process treating real low carbon/nitrogen domestic
wastewater.
AB - The control strategies of energy saving for filamentous sludge bulking were
investigated in the A/O process under low dissolved oxygen (DO) with low
carbon/nitrogen (C/N) ratio, and the dominant filamentous bacteria were
identified by using fluorescent in situ hybridization. Initially, the sludge
volume index reached nearly 500 mL/g and serious bulking occurred when the DO
value was 0.5 mg/L, with Haliscomenobacter hydrossis as the major filamentous
bacteria in the bulking sludge. Later on, the compartment number increased in the
aerobic zone, increasing by this way DO, to control serious bulking. Increasing
DO to 1 mg/L based on the increase of compartment number in the aerobic zone was
the favorable controlling method, which solved the sludge loss, improved the
effluent quality to the national discharge standard and allowed for energy costs
saving. As a result, the effective control method for H. hydrossis filamentous
sludge bulking provided the economical, convenient and longstanding method for
most municipal wastewater treatment plants treating real low C/N domestic
wastewater.
PMID- 28691640
TI - Design of the FINS-TEENS study: A randomized controlled trial assessing the
impact of fatty fish on cognitive performance in adolescents.
AB - AIMS: To describe the rationale, study design, population and dietary compliance
in a randomized controlled trial (RCT) investigating the effect of fatty fish on
cognitive performance and mental health in adolescents. METHOD: In the Fish
Intervention Studies-TEENS (FINS-TEENS) study we individually randomized 478
adolescents (14-15-year-olds) from eight secondary schools in Norway to receive
school meal lunches with fatty fish or meat or n-3 supplements three times a week
for 12 weeks. Demographic factors, psychological tests and biological measures
were collected pre-and post-intervention. Duplicate portions of lunch meals were
collected and individual intake recorded throughout the study. RESULTS: In total,
481 out of 785 adolescents (61%) agreed to participate and 34 (7%) dropped out.
Breakfast consumption was the only group difference in background
characteristics. Analyses of selected nutrients in the lunch meals showed higher
levels of n-3 fatty acids, vitamin D and n-6 fatty acids in the fish compared to
the meat meals. Dietary compliance (score 0-144) revealed that the intake in the
Fish group (mean = 59, standard deviation (SD) = 35) were lower than in the Meat
group (mean = 83, SD = 31, p < 0.01) and Supplement group (mean = 105, SD = 25, p
< 0.01). CONCLUSIONS: The results show that it is possible to conduct a RCT with
fatty fish in a school-based setting. The results also emphasize the importance
of collecting detailed records of dietary compliance, as this information is
important when interpreting and analysing the outcome of dietary interventions.
PMID- 28691641
TI - Decreased long non-coding RNA SPRY4-IT1 contributes to ovarian cancer cell
metastasis partly via affecting epithelial-mesenchymal transition.
AB - Long non-coding RNAs play important roles in the regulation of cellular processes
including cell proliferation, differentiation, and metastasis. The dysregulation
of long non-coding RNAs, such as the SPRY4-IT1 (SPRY4 intronic transcript 1), has
been associated with various types of malignancies. However, the functional roles
and regulatory mechanism of SPRY4-IT1 in ovarian cancer remain to be elucidated.
Here, we quantified the expression level of SPRY4-IT1 in ovarian cancer patients
and found its downregulation in ovarian cancer tissues compared to the adjacent
normal tissues. Patients with lower SPRY4-IT1 expression were associated with a
relatively poor prognosis. In consistency, the expression of SPRY4-IT1 was found
to be reduced in four human ovarian cancer cell lines compared to normal ovarian
epithelial cells. Next, two ovarian cancer cell lines SKOV3 and HO8910 were
employed in vitro assays to investigate biological functions of SPRY4-IT1 in
ovarian cancer. The cell proliferation was reduced following SPRY4-IT1
overexpression in SKOV3/HO8910 cells based on 3-(4,5-dimethylthiazol-2-yl)-2,5
diphenyltetrazolium bromide and colony formation assays. The SPRY4-IT1
overexpression also dramatically arrested cell cycle and promoted cell apoptosis.
Both wound-healing and transwell-based assays demonstrated that cell migration
and invasion were inhibited following SPRY4-IT1 overexpression. Meanwhile,
overexpression of SPRY4-IT1 increased E-cadherin and decreased N-cadherin and
vimentin protein levels, indicating that SPRY4-IT1 may regulate ovarian cancer
cell metastasis through the inhibition of epithelial-mesenchymal transition.
Taken together, our findings suggest that SPRY4-IT1 regulates various cellular
processes of ovarian cancer cells and its downregulation may contribute to
ovarian cancer progression and metastasis partly via affecting the epithelial
mesenchymal transition.
PMID- 28691642
TI - XIAP 3'-untranslated region serves as a competitor for HMGA2 by arresting
endogenous let-7a-5p in human hepatocellular carcinoma.
AB - X-linked inhibitor of apoptosis protein functions as an intrinsic regulator of
apoptosis by inhibition of caspase activity and possesses a pivotal role in human
cancer development and progression. A growing body of literature has demonstrated
that microRNAs lead to the degradation or translational repression of messenger
RNAs by binding to the non-coding region of messenger RNA at the 3'-untranslated
region. Here, we revealed that the expression of HMGA2 is upregulated with X
linked inhibitor of apoptosis protein after transfection of X-linked inhibitor of
apoptosis protein 3'-untranslated region in hepatocellular carcinoma cells,
suggesting that X-linked inhibitor of apoptosis protein 3'-untranslated region
serves as a competitor for microRNAs and prevent the co-targeted messenger RNA,
HMGA2, from being suppressed. We further identified that let-7a-5p could bind to
both the X-linked inhibitor of apoptosis protein 3'-untranslated region and HMGA2
3'-untranslated region. Moreover, we demonstrated that the forced expression of X
linked inhibitor of apoptosis protein 3'-untranslated region increases the
oncogenicity of hepatocellular carcinoma cells in vitro. Cell functional analyses
were performed to examine the association of HMGA2 status and X-linked inhibitor
of apoptosis protein 3'-untranslated region. We have also measured the functional
readout of let-7a-5p and HMGA2, an assay often employed to provide substantial
evidence for the effects of X-linked inhibitor of apoptosis protein 3'
untranslated region on hepatocellular carcinoma cells. In general, our findings
suggest that X-linked inhibitor of apoptosis protein 3'-untranslated region
serves as a competitive endogenous RNA for HMGA2 to activate hepatocellular
carcinoma progression by arresting endogenous let-7a-5p.
PMID- 28691643
TI - Rap2B promotes angiogenesis via PI3K/AKT/VEGF signaling pathway in human renal
cell carcinoma.
AB - Human renal cell carcinoma which is a highly vascular tumor is the leading cause
of death from urologic cancers. Angiogenesis has a pivotal role in oncogenesis
and in the viability and expansion of renal cell carcinoma. Rap2B, as a small
guanosine triphosphate-binding protein of the Ras family, was first discovered in
the early 1990s during the screening of a platelet complementary DNA library.
Previous studies have shown that Rap2B aberrantly expressed in human
carcinogenesis and promoted the development of tumors via multiple signaling
pathways. However, the function of Rap2B in tumor angiogenesis that is necessary
for tumor growth and metastasis remains unknown. In this study, we examined the
role of Rap2B in angiogenesis in renal cell carcinoma by Western blot,
quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, human
umbilical vascular endothelial cells growth assay, and endothelial cell tube
formation assay. We found that Rap2B promoted angiogenesis in vitro and in vivo.
Moreover, our data illustrated that phosphoinositide 3-kinase/AKT signaling
pathway is involved in Rap2B-mediated upregulation of vascular endothelial growth
factor and renal cell carcinoma angiogenesis. Taken together, these results
revealed that Rap2B promotes renal cell carcinoma angiogenesis via
phosphoinositide 3-kinase/AKT/vascular endothelial growth factor signaling
pathway, which suggests that Rap2B is a novel therapeutic target for renal cell
carcinoma anti-angiogenesis therapy.
PMID- 28691644
TI - Distribution and attribution of high-risk human papillomavirus genotypes in
cervical precancerous lesions in China.
AB - While human papillomavirus vaccine was recently approved by China Food and Drug
Administration, mapping of high-risk human papillomavirus distribution and
attribution in cervical precancerous lesions in China becomes critical in
development of a high-risk human papillomavirus-based cervical cancer screening
and prevention strategy. In total, 1016 patients with cervical precancerous
lesions diagnosed in the National Cancer Center/Cancer Hospital, Chinese Academy
of Medical Sciences were analyzed retrospectively, including 111 patients with
low-grade squamous intraepithelial lesions and 905 patients with high-grade
squamous intraepithelial lesions. HPV16, 58, 52, 33, and 31 were the most common
high-risk human papillomavirus genotypes in order of decreasing frequency among
high-risk human papillomavirus-positive high-grade squamous intraepithelial
lesions; this differed from the high-risk human papillomavirus distribution in
low-grade squamous intraepithelial lesions (HPV16, 52, 39, 56, and 58). The
distribution of high-risk human papillomavirus genotypes in single-type
infections for high-grade squamous intraepithelial lesions (HPV16, 58, 33, and
52) was similar to that in multiple-type infections (HPV16, 58, 52, and 33). By
contrast, a more diverse distribution spectrum of high-risk human papillomavirus
genotypes for low-grade squamous intraepithelial lesions was observed between
single-type (HPV16, 52, 39, and 56) and multiple-type infection (HPV52, 68, 58,
59, 39 and 56). A previously published method was adopted to calculate the
fractional proportion of individual high-risk human papillomavirus genotypes in
multiple infections. For this proportional attribution, HPV16 (48.9%), 58
(10.0%), 33 (5.5%), and 52 (5.5%) were the most frequent among all high-grade
squamous intraepithelial lesions, whereas HPV16 (13.2%), 52 (11.6%), 39 (9.5%),
and 56 (7.6%) were the most frequent among all low-grade squamous intraepithelial
lesions. Differences in high-risk human papillomavirus distribution and
proportional attribution in different cervical pathology statuses (high-grade
squamous intraepithelial lesions and low-grade squamous intraepithelial lesions)
demonstrated the critical role of persistent infection of certain high-risk human
papillomavirus such as HPV16, 58, 33, and 52 in carcinogenesis of cervical
cancer. Distinctively high prevalence of HPV58, 33 and 52 in Chinese cervical
intraepithelial neoplasia population, especially in high-grade squamous
intraepithelial lesions, should be taken into consideration in cervical cancer
screening strategy and vaccine development.
PMID- 28691645
TI - A Single Bout of High-Intensity Interval Training Improves Motor Skill Retention
in Individuals With Stroke.
AB - BACKGROUND: One bout of high-intensity cardiovascular exercise performed
immediately after practicing a motor skill promotes changes in the
neuroplasticity of the motor cortex and facilitates motor learning in nondisabled
individuals. OBJECTIVE: To determine if a bout of exercise performed at high
intensity is sufficient to induce neuroplastic changes and improve motor skill
retention in patients with chronic stroke. METHODS: Twenty-two patients with
different levels of motor impairment were recruited. On the first session, the
effects of a maximal graded exercise test on corticospinal and intracortical
excitability were assessed from the affected and unaffected primary motor cortex
representational area of a hand muscle with transcranial magnetic stimulation. On
the second session, participants were randomly assigned to an exercise or a
nonexercise control group. Immediately after practicing a motor task, the
exercise group performed 15 minutes of high-intensity interval training while the
control group rested. Twenty-four hours after motor practice all participants
completed a test of the motor task to assess skill retention. RESULTS: The graded
exercise test reduced interhemispheric imbalances in GABAA-mediated short
interval intracortical inhibition but changes in other markers of excitability
were not statistically significant. The group that performed high-intensity
interval training showed a better retention of the motor skill. CONCLUSIONS: The
performance of a maximal graded exercise test triggers only modest neuroplastic
changes in patients with chronic stroke. However, a single bout of high-intensity
interval training performed immediately after motor practice improves skill
retention, which could potentially accelerate motor recovery in these
individuals.
PMID- 28691646
TI - Participatory methods for Inuit public health promotion and programme evaluation
in Nunatsiavut, Canada.
AB - Engaging stakeholders is crucial for health promotion and programme evaluations;
understanding how to best engage stakeholders is less clear, especially within
Indigenous communities. The objectives of this thesis research were to use
participatory methods to: (1) co-develop and evaluate a whiteboard video for use
as a public health promotion tool in Rigolet, Nunatsiavut, and (2) develop and
validate a framework for participatory evaluation of Inuit public health
initiatives in Nunatsiavut, Labrador. Data collection tools included interactive
workshops, community events, interviews, focus-group discussions and surveys.
Results indicated the whiteboard video was an engaging and suitable medium for
sharing public health messaging due to its contextually relevant elements.
Participants identified 4 foundational evaluation framework components necessary
to conduct appropriate evaluations, including: (1) community engagement, (2)
collaborative evaluation development, (3) tailored evaluation data collection and
(4) evaluation scope. This research illustrates stakeholder participation is
critical to develop and evaluate contextually relevant public health initiatives
in Nunatsiavut, Labrador and should be considered in other Indigenous
communities.
PMID- 28691647
TI - Microbiological diagnosis in revision of infected knee arthroplasties in Denmark.
AB - BACKGROUND: Revision of infected knee arthroplasties is associated with high
failure rates (30-40%). An understanding of the microbiology is important to
optimize treatment and outcome. We describe microbiological diagnostic practice
and diagnosis in revision of infected knee arthroplasties. METHODS: One hundred
and two partial revisions (open debridement and exchange of tibial insert) and
213 two-stage procedures performed due to infection in 275 patients from 1 July
2011 to 30 June 2013 were included and analysed by linkage to data from a
nationwide registry on microbiological test results. RESULTS: 78 (24.8%)
revisions were culture negative, 192 (60.9%) showed monomicrobial growth and 43
(14.3%) polymicrobial growth. Staphylococcus aureus was the most frequent isolate
in mono-culture in 70 (22.2%) revisions and in polymicrobial culture in 15
revisions with a total frequency of 27.0%. Only one case (1.4%) of methicillin
resistance was registered. Coagulase-negative staphylococci (CoNS) were frequent,
sole pathogen in 65 revisions and in polymicrobial cultures in 28 revisions with
a total frequency of 29.5%. A pre-operative knee aspiration was performed in 50%
and preoperative blood cultures were performed in 22% of cases. In 73% of the
preoperative knee-aspirations bacteriological findings were fully or partially in
accordance with intraoperative cultures. In 54% of the later re-revisions due to
infection (treatment-failures) the cultured species differed from or was not
detected at index revision surgery. CONCLUSIONS: The 25% culture negative cases
in combination with only 50% preoperative knee aspirations and prevailing high
failure rates confirm the need for improvement of diagnostic practice and
treatment of infected knee arthroplasties.
PMID- 28691648
TI - Use of a real-time PCR to explore the intensity of Plasmodium spp. infections in
native, endemic and introduced New Zealand birds.
AB - Avian malaria, caused by Plasmodium spp., is an emerging disease in New Zealand
(NZ). To detect Plasmodium spp. infection and quantify parasite load in NZ birds,
a real-time polymerase chain reaction (PCR) (qPCR) protocol was used and compared
with a nested PCR (nPCR) assay. A total of 202 blood samples from 14 bird species
with known nPCR results were tested. The qPCR prevalences for introduced, native
and endemic species groups were 70, 11 and 21%, respectively, with a sensitivity
and specificity of 96.7 and 98%, respectively, for the qPCR, while a sensitivity
and specificity of 80.9 and 85.4% were determined for the nPCR. The qPCR appeared
to be more sensitive in detecting lower levels of parasitaemia. The mean parasite
load was significantly higher in introduced bird species (2245 parasites per 10
000 erythrocytes) compared with endemic species (31.5 parasites per 10 000
erythrocytes). In NZ robins (Petroica longipes), a significantly lower packed
cell volume was found in birds that were positive for Plasmodium spp. compared
with birds that were negative. Our data suggest that introduced bird species,
such as blackbirds (Turdus merula), have a higher tolerance for circulating
parasite stages of Plasmodium spp., indicating that introduced species are an
important reservoir of avian malaria due to a high infection prevalence and
parasite load.
PMID- 28691649
TI - Screening tools for the identification of dementia for adults with age-related
acquired hearing or vision impairment: a scoping review.
AB - BACKGROUND: Cognitive screening tests frequently rely on items being correctly
heard or seen. We aimed to identify, describe, and evaluate the adaptation,
validity, and availability of cognitive screening and assessment tools for
dementia which have been developed or adapted for adults with acquired hearing
and/or vision impairment. METHOD: Electronic databases were searched using
subject terms "hearing disorders" OR "vision disorders" AND "cognitive
assessment," supplemented by exploring reference lists of included papers and via
consultation with health professionals to identify additional literature.
RESULTS: 1,551 papers were identified, of which 13 met inclusion criteria. Four
papers related to tests adapted for hearing impairment; 11 papers related to
tests adapted for vision impairment. Frequently adapted tests were the Mini
Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MOCA).
Adaptations for hearing impairment involved deleting or creating written versions
for hearing-dependent items. Adaptations for vision impairment involved deleting
vision-dependent items or spoken/tactile versions of visual tasks. No study
reported validity of the test in relation to detection of dementia in people with
hearing/vision impairment. Item deletion had a negative impact on the
psychometric properties of the test. CONCLUSIONS: While attempts have been made
to adapt cognitive tests for people with acquired hearing and/or vision
impairment, the primary limitation of these adaptations is that their validity in
accurately detecting dementia among those with acquired hearing or vision
impairment is yet to be established. It is likely that the sensitivity and
specificity of the adapted versions are poorer than the original, especially if
the adaptation involved item deletion. One solution would involve item
substitution in an alternative sensory modality followed by re-validation of the
adapted test.
PMID- 28691650
TI - Behaviour change in overweight and obese pregnancy: a decision tree to support
the development of antenatal lifestyle interventions.
AB - OBJECTIVE: Antenatal healthy lifestyle interventions are frequently implemented
in overweight and obese pregnancy, yet there is inconsistent reporting of the
behaviour-change methods and behavioural outcomes. This limits our understanding
of how and why such interventions were successful or not. DESIGN: The current
paper discusses the application of behaviour-change theories and techniques
within complex lifestyle interventions in overweight and obese pregnancy. The
authors propose a decision tree to help guide researchers through intervention
design, implementation and evaluation. The implications for adopting behaviour
change theories and techniques, and using appropriate guidance when constructing
and evaluating interventions in research and clinical practice are also
discussed. CONCLUSIONS: To enhance the evidence base for successful behaviour
change interventions during pregnancy, adoption of behaviour-change theories and
techniques, and use of published guidelines when designing lifestyle
interventions are necessary. The proposed decision tree may be a useful guide for
researchers working to develop effective behaviour-change interventions in
clinical settings. This guide directs researchers towards key literature sources
that will be important in each stage of study development.
PMID- 28691651
TI - Helminth community structure of 13 species of anurans from Atlantic rainforest
remnants, Brazil.
AB - This study aimed to evaluate the community composition and structure of the
helminths found in 13 anuran species, and to evaluate whether this parasite
community is determined by anuran characteristics. We found that the helminth
fauna of the amphibians from five anuran families consisted of 13 taxa and that
Cosmocercidae gen. sp. was the most prevalent taxon, followed by Oswaldocruzia
subauricularis. Host body size was a determining factor of the composition and
structure of the parasitic fauna. Helminth abundance and richness were positively
correlated with host body size. The host Leptodactylus latrans had the highest
helminth richness (n = 8). The frog Hypsiboas faber had the greatest helminth
diversity (H' = 0.711). The mean helminth species richness and diversity differed
significantly between host species (P < 0.05). Taken together, our data indicate
that, in sympatric species of amphibians, the morphological and behavioural
characteristics of the hosts are important for structuring the helminth parasite
communities.
PMID- 28691652
TI - Migration of Fasciola hepatica newly excysted juveniles is inhibited by high
mannose and oligomannose-type N-glycan-binding lectins.
AB - Fasciola hepatica has both zoonotic importance and high economic impact in
livestock worldwide. After ingestion by the definitive host, the Newly Excysted
Juveniles (NEJ) penetrate the intestine before reaching the peritoneal cavity.
The role of some NEJ-derived proteins in invasion has been documented, but the
role of NEJ glycans or lectin-binding receptors during initial infection in the
gut is still unknown. To address these questions, the migration of NEJ through
rat intestine was recorded at 30 min intervals up to 150 min by two ex vivo
methods. Firstly, jejunal sheets were challenged with NEJ incubated with
biotinylated lectins. Secondly, untreated NEJ were incubated with distal jejunum
pre-treated with lectins. Both Concanavalin A (ConA) and Galanthus nivalis (GNL),
which recognize mannose-type N-glycans, significantly inhibited NEJ migration
across the jejunum. Most of the lectins bound to the tegument and oral sucker of
the NEJ, but only ConA and GNL maintained this interaction over 150 min. None of
the lectins examined significantly reduced NEJ migration when pre-incubated with
jejunal sheets, suggesting that host glycans might not be essential for initial
binding/recognition of the gut by NEJ. Agents capable of blocking mannose-type N
glycans on the NEJ tegument may have potential for disrupting infection.
PMID- 28691653
TI - Molecular, biochemical characterization and assessment of immunogenic potential
of cofactor-independent phosphoglycerate mutase against Leishmania donovani: a
step towards exploring novel vaccine candidate.
AB - Despite immense efforts, vaccine against visceral leishmaniasis has yet not been
developed. Earlier our proteomic study revealed a novel protein, cofactor
independent phoshoglycerate mutase (LdiPGAM), an important enzyme in glucose
metabolism, in T helper cells type 1 (Th1) stimulatory region of soluble
Leishmania donovani antigen. In this study, LdiPGAM was biochemically and
molecularly characterized and evaluated for its immunogenicity and prophylactic
efficacy against L. donovani. Immunogenicity of recombinant LdiPGAM (rLdiPGAM)
was initially assessed in naive hamsters immunized with it by analysing mRNA
expression of inducible nitric oxide (NO) synthase (iNOS) and other Th1/T helper
cells type 2 cytokines, which revealed an upregulation of Th1 cytokines along
with iNOS. Immunogenicity of rLdiPGAM was further evaluated in lymphocytes of
treated Leishmania-infected hamsters and peripheral blood mononuclear cells of
Leishmania patients in clinical remission by various parameters, viz.
lymphoproliferation assay and NO production (hamsters and patients) and levels of
various cytokines (patients). rLdiPGAM induced remarkable Lymphoproliferative
response and NO production in treated Leishmania-infected hamsters as well as in
patients and increase in interferon gamma (IFN-gamma), interleukin-12 (IL-12p40)
responses in Leishmania patients in clinical remission. Vaccination with rLdiPGAM
exerted considerable prophylactic efficacy (73%) supported by increase in mRNA
expression of iNOS, IFN-gamma and IL-12p40 with decrease in transforming growth
factor beta and interleukin-10. Above results indicate the importance of rLdiPGAM
protein as a potential vaccine candidate against visceral leishmaniasis.
PMID- 28691654
TI - Thalassotalea crassostreae sp. nov., isolated from Pacific oyster.
AB - A Gram-staining-negative, aerobic, rod-shaped bacterial strain, designated
LPB0090T, was isolated from the Pacific oyster, Crassostreagigas, collected from
the Yeongheung Island, Korea (37 degrees 15' 16.1" N; 126 degrees 29' 46.5" E).
The complete genome sequence of LPB0090T (accession number CP017689) was 3 861
670 bp long with a DNA G+C content of 38.8 mol%. The genome included 3245 protein
coding genes and six copies of rRNA operons. On the basis of the results of 16S
rRNA gene sequence analysis, LPB0090T was found to form an independent phyletic
line within the genus Thalassotalea, with 94.7-96.0 % sequence similarities to
the previously known species of the genus. The isoprenoid quinone (Q-8) and major
fatty acids (C16 : 0, C17 : 1 omega8c, and C16 : 1 omega7c and/or C16 : 1
omega6c) of the isolate were similar to those of the other members of the genus
Thalassotalea. A number of phenotypic features, however, distinguished LPB0090T
from its closest neighbour Thalassotalea ponticola as well as other species of
the genus Thalassotalea. On the basis of the phylogenetic, genomic and phenotypic
data presented in this study, the strain was classified as representing a novel
species of the genus Thalassotalea. Therefore, the name Thalassotalea
crassostreae sp. nov. is proposed for the isolate. The type strain is LPB0090T
(=KACC 18695T=JCM 31189T).
PMID- 28691655
TI - Sphingomonas spermidinifaciens sp. nov., a novel bacterium containing spermidine
as the major polyamine, isolated from an abandoned lead-zinc mine and emended
descriptions of the genus Sphingomonas and the species Sphingomonas yantingensis
and Sphingomonas japonica.
AB - A yellow-pigmented bacterial strain, designated 9NM-10T, was isolated from an
abandoned lead-zinc mine in Meizhou, Guangdong Province, China. Cells were
strictly aerobic, Gram-stain-negative and motile with a polar monotrichous
flagellum. Phylogenetic analyses based on 16S rRNA gene sequences revealed that
strain 9NM-10T belongs to the genus Sphingomonas and was most closely related to
Sphingomonas yantingensis JCM 19201T and Sphingomonas japonica JCM 15438T. DNA
DNA relatedness values between strain 9NM-10T and these two type strains were
43.6+/-1.3 and 35.4+/-0.9 %, respectively. It contained Q-10 as the predominant
respiratory quinone and the major cellular fatty acids were C18 : 1omega7c, C16 :
0, C17 : 1omega6c and summed feature 3 (C16 : 1omega7c and/or C16 : 1omega6c).
The genomic DNA G+C content of strain 9NM-10T was 68.7+/-0.2 mol%. The polar
lipids were sphingoglycolipid, phosphatidylglycerol, phosphatidylcholine,
phosphatidylethanolamine, diphosphatidylglycerol, an unidentified phospholipid
and three unidentified lipids. Strain 9NM-10T contained spermidine as the major
polyamine. On the basis of phenotypic, phylogenetic and chemotaxonomic analyses,
strain 9NM-10T is considered to represent a novel species of the genus
Sphingomonas, for which the name Sphingomonas spermidinifaciens sp. nov. is
proposed. The type strain is 9NM-10T (=GDMCC 1.657T=DSM 27571T). Descriptions of
the genus of Sphingomonas and the species Sphingomonas yantingensis and
Sphingomonas japonica were also emended in this study.
PMID- 28691656
TI - Mutational analysis of the MS2 lysis protein L.
AB - Small single-stranded nucleic acid phages effect lysis by expressing a single
protein, the amurin, lacking muralytic enzymatic activity. Three amurins have
been shown to act like 'protein antibiotics' by inhibiting cell-wall
biosynthesis. However, the L lysis protein of the canonical ssRNA phage MS2, a 75
aa polypeptide, causes lysis by an unknown mechanism without affecting net
peptidoglycan synthesis. To identify residues important for lytic function,
randomly mutagenized alleles of L were generated, cloned into an inducible
plasmid and the transformants were selected on agar containing the inducer. From
a total of 396 clones, 67 were unique single base-pair changes that rendered L
non-functional, of which 44 were missense mutants and 23 were nonsense mutants.
Most of the non-functional missense alleles that accumulated in levels comparable
to the wild-type allele are localized in the C-terminal half of L, clustered in
and around an LS dipeptide sequence. The LS motif was used to align L genes from
ssRNA phages lacking any sequence similarity to MS2 or to each other. This
alignment revealed a conserved domain structure, in terms of charge, hydrophobic
character and predicted helical content. None of the missense mutants affected
membrane-association of L. Several of the L mutations in the central domains were
highly conservative and recessive, suggesting a defect in a heterotypic protein
protein interaction, rather than in direct disruption of the bilayer structure,
as had been previously proposed for L.
PMID- 28691657
TI - A relevant in vitro human model for the study of Zika virus antibody-dependent
enhancement.
AB - Zika virus (ZIKV) is a mosquito-borne flavivirus that has recently been
responsible for a serious outbreak of disease in South and Central America.
Infection with ZIKV has been associated with severe neurological symptoms and the
development of microcephaly in unborn fetuses. Many of the regions involved in
the current outbreak are known to be endemic for another flavivirus, dengue virus
(DENV), which indicates that a large percentage of the population may have pre
existing DENV immunity. Thus, it is vital to investigate what impact pre-existing
DENV immunity has on ZIKV infection. Here, we use primary human myeloid cells as
a model for ZIKV enhancement in the presence of DENV antibodies. We show that
sera containing DENV antibodies from individuals living in a DENV-endemic area
are able to enhance ZIKV infection in a human macrophage-derived cell line and
primary human macrophages. We also demonstrate altered pro-inflammatory cytokine
production in macrophages with enhanced ZIKV infection. Our study indicates an
important role for pre-existing DENV immunity on ZIKV infection in primary human
immune cells and establishes a relevant in vitro model to study ZIKV antibody
dependent enhancement.
PMID- 28691658
TI - Bizionia sediminis sp. nov., isolated from coastal sediment.
AB - A Gram-stain-negative, aerobic, non-gliding, rod-shaped and orange-coloured
bacterium, designated strain P131T, was isolated from marine sediment of the
coast of Weihai, China, and subjected to a polyphasic study. Strain P131T was
found to grow optimally at 28-30 degrees C, at pH 7.0-7.5 and in the presence of
2-3 % (w/v) NaCl. In a phylogenetic analysis based on 16S rRNA gene sequences,
strain P131T was found to belong to the genus Bizionia and exhibited 94.6-97.0 %
16S rRNA gene sequence similarity with recognized Bizionia species. The dominant
cellular fatty acids of strain P131T were identified as iso-C15 : 0, iso-C15 : 0
G, iso-C17 : 0 3-OH and iso-C17 : 1omega9c. The predominant polar lipids were
phosphatidylethanolamine, phospholipid, two aminolipids and two unidentified
lipids. The predominant respiratory quinone was menaquinone MK-6 and the DNA G+C
content was 36.7 mol%. On the basis of the phylogenetic and phenotypic evidence
presented, strain P131T represents a novel species of the genus Bizionia, for
which the name Bizionia sediminis sp. nov. is proposed. The type strain is P131T
(=KCTC 42587T=MCCC 1H00124T).
PMID- 28691660
TI - Endoribonuclease type II toxin-antitoxin systems: functional or selfish?
AB - Most bacterial genomes have multiple type II toxin-antitoxin systems (TAs) that
encode two proteins which are referred to as a toxin and an antitoxin. Toxins
inhibit a cellular process, while the interaction of the antitoxin with the toxin
attenuates the toxin's activity. Endoribonuclease-encoding TAs cleave RNA in a
sequence-dependent fashion, resulting in translational inhibition. To account for
their prevalence and retention by bacterial genomes, TAs are credited with
clinically significant phenomena, such as bacterial programmed cell death,
persistence, biofilms and anti-addiction to plasmids. However, the programmed
cell death and persistence hypotheses have been challenged because of conceptual,
methodological and/or strain issues. In an alternative view, chromosomal TAs seem
to be retained by virtue of addiction at two levels: via a poison-antidote
combination (TA proteins) and via transcriptional reprogramming of the downstream
core gene (due to integration). Any perturbation in the chromosomal TA operons
could cause fitness loss due to polar effects on the downstream genes and hence
be detrimental under natural conditions. The endoribonucleases encoding
chromosomal TAs are most likely selfish DNA as they are retained by bacterial
genomes, even though TAs do not confer a direct advantage via the TA proteins.
TAs are likely used by various replicons as 'genetic arms' that allow the
maintenance of themselves and associated genetic elements. TAs seem to be the
'selfish arms' that make the best use of the 'arms race' between bacterial
genomes and plasmids.
PMID- 28691659
TI - Proline utilization system is required for infection by the pathogenic alpha
proteobacterium Brucella abortus.
AB - Proline utilization (Put) systems have been described in a number of bacteria;
however, the importance and functionality of the Put system in the intracellular
pathogen Brucellaabortus has not been explored. Generally, bacterial Put systems
are composed of the bifunctional enzyme proline dehydrogenase PutA and its
transcriptional activator PutR. Here, we demonstrate that the genes putA
(bab2_0518) and putR (bab2_0517) are critical for the chronic infection of mice
by B. abortus, but putA and putR are not required for the survival and
replication of the bacteria in naive macrophages. Additionally, in vitro
experiments revealed that putR is necessary for the ability of the bacteria to
withstand oxidative stress, as a DeltaputR deletion strain is hypersensitive to
hydrogen peroxide exposure. Quantitative reverse transcription-PCR and putA-lacZ
transcriptional reporter studies revealed that PutR acts as a transcriptional
activator of putA in Brucella, and electrophoretic mobility shift assays
confirmed that PutR binds directly to the putA promoter region. Biochemical
analyses demonstrated that a purified recombinant B. abortus PutA protein
possesses quintessential proline dehydrogenase activity, as PutA is capable of
catalysing the conversion of proline to glutamate. Altogether, these data are the
first to reveal that the Put system plays a significant role in the ability of B.
abortus to replicate and survive within its host, as well as to describe the
genetic regulation and biochemical activity of the Put system in Brucella.
PMID- 28691661
TI - Drosophila microRNA modulates viral replication by targeting a homologue of
mammalian cJun.
AB - MicroRNAs (miRNAs) are important regulators of biological processes, including
host-virus interaction. This study investigated the involvement of Drosophila
melanogaster miR-8-5p in host-virus interaction. Drosophila flies and cells
challenged with Drosophila C virus (DCV) were found to have lower miR-8-5p
abundance compared to uninfected samples. Lowering miR-8-5p abundance by
experimental inhibition of the miRNA led to an increase in viral accumulation,
suggesting that the observed decrease in the miR-8-5p abundance during DCV
infection enhances viral replication. miR-8-5p putative targets were identified
and included dJun, a transcription factor gene whose mammalian homologue cJun is
induced by various viruses through kinase activation. Increasing miR-8-5p
abundance using miR-8-5p mimics resulted in a decrease in dJun and GFP reporter
levels. Furthermore, when the putative target in dJun was mutated, addition of
miR-8-5p mimics did not result in the same antagonistic effect on dJun. These
results show negative regulation of dJun by miR-8-5p and suggest that an miRNA
mediated pathway is involved in dJun regulation during viral infection. To
analyse the role of dJun during DCV infection, dJun was knocked down in cells
prior to DCV infection. Knockdown of dJun decreased DCV replication, providing
evidence that dJun up-regulation that is concomitant with miR-8-5p down
regulation during DCV infection supports viral replication. These results
highlight the role of miRNA in regulating the transcription factor gene dJun and
uncover a previously unrecognized mechanism by which dJun is regulated during
host-virus interaction.
PMID- 28691662
TI - Role of the inner-membrane histidine kinase RcsC and outer-membrane lipoprotein
RcsF in the activation of the Rcs phosphorelay signal transduction system in
Escherichia coli.
AB - The Rcs phosphorelay signal transduction system of Escherichia coli controls
genes for capsule production and many other envelope-related functions and is
implicated in biofilm formation. The outer-membrane lipoprotein RcsF is an
essential component of the Rcs system. Mislocalization of RcsF to the periplasm
or the cytoplasmic membrane leads to high activation of the Rcs system,
suggesting that RcsF functions by interacting with the cytoplasmic membrane
component(s) of the system in activating the system. This is consistent with the
result reported by Cho et al. (Cell159, 1652-1664, 2014) showing that RcsF
interacts with the periplasmic domain (YrfFperi) of the inner-membrane protein
YrfF (IgaA in Salmonella enterica serovar Typhimurium), which is a negative
regulator of the Rcs system. In this study we show that RcsF also interacts with
the periplasmic domain of the innermembrane-localized histidine kinase RcsC
(RcsCperi). RcsCperi, which was secreted to the periplasm by fusion to maltose
binding protein, titrated RcsF's activating effect. A bimolecular fluorescence
complementation experiment showed interaction of RcsF with RcsCperi, as well as
with YrfFperi. We conclude that RcsF interacts with the periplasmically exposed
region of RcsC, as well as with that of YrfF.
PMID- 28691663
TI - Quantitative trait loci in pepper control the effective population size of two
RNA viruses at inoculation.
AB - Infection of plants by viruses is a complex process involving several steps:
inoculation into plant cells, replication in inoculated cells and plant
colonization. The success of the different steps depends, in part, on the viral
effective population size (Ne), defined as the number of individuals passing
their genes to the next generation. During infection, the virus population will
undergo bottlenecks, leading to drastic reductions in Ne and, potentially, to the
loss of the fittest variants. Therefore, it is crucial to better understand how
plants affect Ne. We aimed to (i) identify the plant genetic factors controlling
Ne during inoculation, (ii) understand the mechanisms used by the plant to
control Ne and (iii) compare these genetic factors with the genes controlling
plant resistance to viruses. Ne was measured in a doubled-haploid population of
Capsicum annuum. Plants were inoculated with either a Potato virus Y (PVY)
construct expressing the green fluorescent protein or a necrotic variant of
Cucumber mosaic virus (CMV). Newas assessed by counting the number of primary
infection foci on cotyledons for PVY or the number of necrotic local lesions on
leaves for CMV. The number of foci and lesions was correlated (r=0.57) and showed
a high heritability (h2=0.93 for PVY and h2=0.98 for CMV). The Ne of the two
viruses was controlled by both common quantitative trait loci (QTLs) and virus
specific QTLs, indicating the contribution of general and specific mechanisms.
The PVY-specific QTL colocalizes with a QTL that reduces PVY accumulation and the
capacity to break down a major-effect resistance gene.
PMID- 28691664
TI - Impact of naturally occurring variation in the human papillomavirus (HPV) 33
capsid proteins on recognition by vaccine-induced cross-neutralizing antibodies.
AB - We investigated naturally occurring variation within the major (L1) and minor
(L2) capsid proteins of human papillomavirus (HPV) genotype 33. Pseudoviruses
(PsV) representing HPV33 lineages A1, A2, A3, B and C exhibited comparable
particle-to-infectivity ratios and morphology but demonstrated a decreased
sensitivity (A2, A3, B and C) to cross-neutralization by HPV vaccine antibodies
compared to the A1 sublineage. Chimeric PsVs demonstrated that these differences
in sensitivity were due to polymorphisms in the L1 protein, with little or no
influence from variation within the L2 protein. Site-directed mutagenesis of the
L1 gene identified the DE loop residue 133 and the FG residue 266 as being
critical for conferring this differential sensitivity. The use of HPV33 homology
models based upon the HPV16 crystal structure suggested that they are likely to
act independently on more than one antibody epitope. These data improve our
understanding of the potential impact of natural capsid variation on recognition
by vaccine antibodies.
PMID- 28691665
TI - Cold-stress response during the stationary-growth phase of Antarctic and
temperate-climate Penicillium strains.
AB - Cold-induced oxidative stress during the aging of three Penicillium strains (two
Antarctic and one from a temperate region) in stationary culture was documented
and demonstrated a significant increase in the protein carbonyl content, the
accumulation of glycogen and trehalose, and an increase in the activities of
antioxidant enzymes (superoxide dismutase and catalase). The cell response to a
temperature downshift depends on the degree of stress and the temperature
characteristics of the strains. Our data give further support for the role of
oxidative stress in the aging of fungi in stationary cultures. Comparing the
present results for the stationary growth phase with our previous results for the
exponential growth phase was informative concerning the relationship between the
cold-stress response and age-related changes in the tested strains. Unlike the
young cells, stationary-phase cultures demonstrated a more pronounced level of
oxidative damage, as well as decreased antioxidant defence.
PMID- 28691666
TI - Hymenobacter tenuis sp. nov., isolated from wastewater of an acidic water
neutralization facility.
AB - A non-motile, red-pink-coloured, rod-shaped bacterium, designated strain POB6T,
was isolated from a wastewater treatment facility, Republic of Korea. Cells were
Gram-stain-negative, aerobic, catalase-positive and oxidase-negative. The major
fatty acids were iso-C15 : 0, C16 : 1omega5c, summed feature 3 (C16 : 1omega6c
and/or C16 : 1omega7c) and summed feature 4 (iso-C17 : 1 I and/or anteiso-C17 : 1
B). The strain contained menaquinone MK-7 as the only isoprenoid quinone,
phosphatidylethanolamine as the major polar lipid and sym-homospermidine as the
major polyamine. The DNA G+C content was 61 mol%. A phylogenetic tree based on
16S rRNA gene sequences showed that strain POB6T forms a distinct evolutionary
lineage within the radiation enclosing the members of the genus Hymenobacter,
sharing the highest similarity with Hymenobacterrigui WPCP131T (97.5 %) followed
by Hymenobacter xinjiangensis X2-1gT (97.2 %), Hymenobacter perfusus A1-12T (97.2
%) and Hymenobacter gelipurpurascens Txg-1T (97.1 %). A number of phenotypic
characteristics distinguished strain POB6T from related members of the genus
Hymenobacter. On the basis of the evidence presented in this study, a novel
species, Hymenobacter tenuis sp. nov., is proposed, with POB6T (=KCTC 52271T=JCM
31659T) as the type strain.
PMID- 28691667
TI - Precision surgery for older cancer patients.
PMID- 28691668
TI - Correct information to patients undergoing breast-conserving surgery: the
medicolegal significance.
AB - Many of the women newly diagnosed with breast cancer not have access to all the
information they need to make the surgical and treatment choices that are most
appropriate for them. Research clearly shows that lumpectomy and other breast
conserving surgeries are just as safe as mastectomy for most women with early
stage disease, and yet approximately half will undergo the more disfiguring
procedures, but many healthy women who have strong family histories of breast
cancer consider prophylactic mastectomies, and their decisions are also based on
very limited information, because there are few studies showing the effectiveness
of that procedure. This paper delineates how to avoid limited information and
biased recommendations is important for a conscious and informed choice by the
patients.
PMID- 28691669
TI - Spontaneous chronic subdural hematoma in young adult: the role of missing
coagulation facto.
AB - AIM: Chronic subdural hematoma (CSDH) is typically in elderly and rarely in young
people. To prevent complications and re-bleeding after surgical treatment of CSDH
it is important to assess the risk factors as coagulation disorders especially in
young patients (below 65 years) with no history of head trauma, alcohol abuse or
anticoagulant therapy. PATIENTS AND METHODS: This study consists of 16 patients
(12 males, 4 females) with age ranging from 27 to 59 years (median 48,25 years)
operated for CSDH. All patients are submitted to routine coagulation parameters
pre-operatively and complete screening for unknown coagulation deficit in the
follow-up. RESULTS: Factor VII was altered in 6 out of 16 patients and one
patient had the alteration of the Von Willebrand factor. Recurrence occurred in 4
out of 16 patients and all of these patients were positive for factor VII
deficiency. Three pts were in therapy with ASA. No patients were alcoholists or
suffered from hematological disease. CONCLUSION: In this study we documented that
the decreased activity of VII factor may play a role in the pathophysiology and
recurrence of spontaneous CSDH in young adults. We suggest that for young
patients aged under 65 y.o. suffered from CSDH the screening of coagulation
factors is useful to planning a safely and correct surgical therapy.
PMID- 28691670
TI - Non-Occlusive Mesenteric Ischemia (NOMI) in Parkinson's disease: case report.
AB - Non-occlusive mesenteric ischemia (NOMI) is a severe pathological condition
characterized by signs and symptoms of bowel obstruction, intestinal necrosis
resulting from acute and/or chronic inadequate blood perfusion, in the absence of
an organic vascular obstruction detectable by imaging techniques. A 64 years old
man case with a history of Parkinson's disease in high-functioning levodopa
treatment is presented. Clinical and radiological signs of intestinal obstruction
were observed. He underwent surgical operation with total colectomy and terminal
ileostomy for generalized secondary peritonitis due to perforation of sigmoid
colon. Ischemic pancolitis was first suspected. In third post-operative day a
contrastenhanced CT scan was performed in the evidence of fever and sub-occlusive
symptoms. It was found absence of reliable evidence of vascular changes; superior
mesenteric artery and vein patency is maintained A NOMI was then diagnosed. NOMI
represents about 0.04% of mesenteric artery diseases. It is correlated with a
poor prognosis with a mortality estimated of 70-90%. Parkinson's disease,
considering neurodegenerative alterations that characterize it, can be considered
as a predisposing factor. The combined treatment with high doses of levodopa and
vasodilators, such as PGE (Prostaglandin E), can contribute to an improvement in
prognosis.
PMID- 28691671
TI - Bilateral primary ovarian non-Hodgkin's lymphoma and fertility preservation: 5
year follow-up.
AB - AIM: Primary ovarian non-Hodgkin's lymphoma is a very rare disease. Median age at
diagnosis is estimated at 42 years, something that leads to fertility
preservation issues in many cases. This was a case report study, presenting a
rare case of bilateral primary ovarian non-Hodgkin's lymphoma. CASE REPORT: A 38
year old nulliparous woman, underwent exploratory laparotomy because of bilateral
ovarian masses. Left salpingooophorectomy, partial omentectomy and excision of an
ovarian mass of the right ovary was performed. Great effort in order to preserve
healthy ovarian tissue of the right ovary as well as the right fallopian tube was
given, due to fertility reasons. Final histology showed bilateral diffuse large B
cell primary ovarian non-Hodgkin's lymphoma. Postoperatively, the patient
underwent chemotherapy with the CHOP regimen in combination with rituximab. Five
years after initial diagnosis, the patient remains well with normal menstrual
cycle, without evidence of recurrence. DISCUSSION: Fertility preservation issues
in some cases of rare gynecological malignancies could be managed via minimally
invasive oncological approach.
PMID- 28691672
TI - Ingestion of foreign bodies among prisoners: a ten years retrospective study at
University Hospital of Southern Italy.
AB - INTRODUCTION: We studied 21 episodes of ingestion of foreign bodies (IFO) among
15 prisoners. PATIENTS AND METHODS: Rectrospective research in pts admitted to
emergency from June 2005 to May 2105. Ingestion, management and pts outcome were
analyzed. Prisoners with previous esophagogastroduodenal disease were excluded.
RESULTS: All pts were males and ingestions were intentional.
Esophagogastroduoduenoscopy (EGDS) was performed in 10pts (8 cases with
successful removal, 1 case we did not find anything e 1 of unsuccessful EGDS,
that required emergency surgey. 9 pts rejected EGDS: in 2 pts were not
necessary.Among the 9 pts that rejected EGDS, 5 discharged voluntary. No
mortality neither morbidity. Only 1 pt required surgery.The IFO were 34 (23
sharp, 6 flat,5 indefined). We did not observe any food bolus impaction. Multiple
ingestion was found in 11 pts. Recurrent episodes were found in 4 pts.
DISCUSSION: Almost all episodes can be treated conservatively with observation
and endoscopy but the management of this pts has a financial impact on healthcare
cost and on security costs. Prevention strategies are important to predict
patient group at high risk for recurrent IFO.
PMID- 28691673
TI - Gastric paraganglioma: case report and review of the literature.
AB - Very few cases of gastric paragangliomas have been reported in the literature to
date. We report a rare case of parietal gastric paraganglioma fortuitously
detected during intraoperative exploration. A 82-years-old woman presented to our
emergency room for abdominal pain. On physical examination abdomen was painful on
palpation and Blumberg's sign was present. The laboratory exams showed a
neutrophilia in absence of leukocytosis. Acute appendicitis was suspected and a
laparoscopy was performed. At exploration, the vermiform appendix was normal
while a lumpy, hard-fibrous and white-pinkish extraluminal lesion of the anterior
wall of the gastric body near the greater curvature of about 2 cm in diameter was
present. Laparoscopic resection of the gastric lesion was performed. The patient
was discharged in good condition in the fourth postoperative day. Pathologic
examination revealed a gangliocitic paraganglioma. The patient is alive and well
without evidence of relapse 6 months after surgery. Gastric paraganglioma is a
very rare tumor and its diagnosis is very difficult. Surgical excision is the
treatment of choice which can be performed successfully with laparoscopy.
PMID- 28691674
TI - Choosing the individual rehabilitation program for patients with intermittent
claudication.
AB - This study is aimed at identifying the collateral circulation in case of femoral
aorta-iliac axis obstruction, with the purpose of a more correct therapeutic
indication being either medical or surgical or physiotherapeutic or combined.
PMID- 28691676
TI - Alla ricerca dei chirurghi perduti CHARLES PIERRE DENONVILLIERS E LA "SUA"
APONEUROSI.
PMID- 28691675
TI - Incidental thyroid carcinomas. A retrospective study.
AB - AIM: The aim of the present study is to report our series of incidental thyroid
carcinomas in the last 15 years and their follow-up, discussing therapeutics
indications and surgical choices. PATIENTS AND METHODS: We have considered 1793
patients operated on Surgical Sciences Department of "Sapienza" University of
Rome from January 1, 2001 to December 31, 2015. The study was conducted on 83
totally thyroidectomized patients with a real incidental thyroid carcinoma, by
clinical, laboratory and instrumental controls. Whole-body scan was the most
important test in postoperative evaluation. RESULTS: In our series, the incidence
of incidental carcinomas was 4.62%. Compared to the total number of cancer
patients, the percentage is 21,9%. In 15.66% of cases there was multifocality and
in 7.23% also bilaterality. Regarding the histological type, in all cases they
were papillary carcinoma. The size of the neoplastic lesions ranged from a
minimum of 3 to a maximum of 10 mm. Whole-body scan revealed lymph node
metastasis in 57.69% of patients. DISCUSSION: Comparing these data with our
previous studies we have seen a significant increase in incidence of incidental
thyroid carcinomas over the years. Our therapeutical choice is total
thyroidectomy and complection thyroidectomy after lobectomy, because of a
relevant percentage of multifocality and/or bilaterality of these tumors. Many
Authors on the contrary prefer a more conservative approach invoking the good
prognosis of these tumors. The 57.69% of lymph node metastasis at postoperative
whole-body scan comfort us in our setting. CONCLUSION: Incidental thyroid
carcinomas are not uncommon. We consider only tumors until 1 cm in diameter.
Multifocality and bilaterality are often present such as occult lymph node
metastasis. Our therapeutical choice is total thyroidectomy in order to conduct a
proper follow-up.
PMID- 28691677
TI - Feasibility of a Lifestyle Redesign(r)-Inspired Intervention for Well Older
Adults.
AB - OBJECTIVE: We examined the feasibility of Aging Well by Design, a Lifestyle
Redesign(r)-inspired intervention for community-dwelling older adults. The
original Lifestyle Redesign program was shortened to 3 mo and implemented as a
community outreach program of a major health care system. METHOD: Community
dwelling older adults participated in the 12-wk program, which emphasized an
occupational approach to healthy aging. Outcomes evaluated were recruitment,
attendance, resource use, participant satisfaction, and subjective benefit to
participants. RESULTS: The 13 participants, ages 66-88 yr, attended an average of
10 of 12 sessions. The intervention was completed as planned, physical resources
were suitable, and financial resources were adequate. Participants expressed
satisfaction with the program's facilitator, group discussions, and materials.
Perceived benefits were social relationships, awareness of community resources,
and change in attitude toward aging. CONCLUSION: Implementation of a 3-mo
Lifestyle Redesign-inspired program within a health care system was feasible.
PMID- 28691678
TI - Pragmatic Language Outcomes of Children With Attention Deficit Hyperactivity
Disorder After Therapist- and Parent-Delivered Play-Based Interventions: Two One
Group Pretest-Posttest Studies With a Longitudinal Component.
AB - OBJECTIVE: The pragmatic language outcomes of children with attention deficit
hyperactivity disorder (ADHD) were explored across two feasibility studies.
METHOD: Five children with ADHD (ages 6-11 yr), their parents, and 5 typically
developing peers completed an assessment 18 mo after a therapist-delivered
intervention (Study 1). Participants then completed a parent-delivered
intervention (Study 2). Blinded ratings of peer-to-peer play interactions
documented changes in children's pragmatic language 18 mo after the Study 1
intervention and before, immediately after, and 1 mo after the Study 2
intervention. Nonparametric statistics and Cohen's d were used to measure change.
RESULTS: Children's pragmatic language outcomes were maintained 18 mo after the
therapist-delivered intervention and significantly improved from before to 1 mo
after the parent-delivered intervention. CONCLUSION: Interventions involving
occupational therapist and speech-language pathologist collaboration, play, and
parent and peer involvement may facilitate children's pragmatic language skills.
PMID- 28691680
TI - Treating hepatitis C virus in patients with chronic renal failure.
PMID- 28691681
TI - Is it time to change NAFLD and NASH nomenclature?
PMID- 28691682
TI - Surrogate endpoints for clinical trials in non-alcoholic steatohepatitis.
PMID- 28691683
TI - Surrogate endpoints for clinical trials in non-alcoholic steatohepatitis -
Author's reply.
PMID- 28691686
TI - Oesophageal dysphagia: a stepwise approach to diagnosis and management.
AB - Dysphagia is a common symptom in the general population. Incidence varies
depending on the specific definition used. A good medical history is vital for
distinguishing true oesophageal dysphagia from oropharyngeal dysphagia or other
causes. Oesophageal dysphagia is a so-called red flag alarm symptom requiring
oesophagogastroduodenoscopy. However, even after investigations including
oesophagogastroduodenoscopy (with biopsy), barium swallow, and oesophageal
manometry, no obstructive cause may be found. This Review suggests an algorithm
of history-taking and investigation to allow the causes of non-obstructive
dysphagia to be identified, including functional dysphagia. The Review then
discusses management strategies and outcomes for functional dysphagia.
PMID- 28691688
TI - Correction to Lancet Gastroenterol Hepatol 2017; 2: 540-41.
PMID- 28691687
TI - Pancreaticobiliary maljunction and congenital biliary dilatation.
AB - Pancreaticobiliary maljunction is a congenital malformation in which the
pancreatic and bile ducts join outside the duodenal wall, usually forming a long
common channel. Because the action of the sphincter of Oddi does not regulate the
function of the pancreaticobiliary junction in patients with pancreaticobiliary
maljunction, two-way regurgitation occurs. Reflux of pancreatic juice into the
biliary tract is associated with a high incidence of biliary cancer. Biliary
carcinogenesis in patients with pancreaticobiliary maljunction is thought to
follow the hyperplasia, dysplasia, then carcinoma sequence due to chronic
inflammation caused by pancreatobiliary reflux. Pancreaticobiliary maljunction is
diagnosed when an abnormally long common channel is evident on imaging studies.
Congenital biliary dilatation involves both local dilatation of the extrahepatic
bile duct, including the common bile duct, and pancreaticobiliary maljunction.
Extrahepatic bile duct resection is the standard surgery for congenital biliary
dilatation. However, complete excision of the intrapancreatic bile duct and
removal of stenoses of the hepatic ducts are necessary to prevent serious
complications after surgery.
PMID- 28691689
TI - A case of a focal oedematous reaction induced by rituximab overlying lupus
erythematosus tumidus.
PMID- 28691690
TI - Enhanced superconductivity in SnSb under pressure: a first principles study.
AB - First principles electronic structure calculations reveal both SnP and SnSb to be
stable in the NaCl structure. In SnSb, a first order phase transition from NaCl
to CsCl type structure is observed at around 13 GPa, which is also confirmed from
enthalpy calculations and agrees well with experimental and other theoretical
reports. Calculations of the phonon spectra, and hence the electron-phonon
coupling [Formula: see text] and superconducting transition temperature T c, were
performed at zero pressure for both the compounds, and at high pressure for SnSb.
These calculations report [Formula: see text] of [Formula: see text] K and
[Formula: see text] K for SnP and SnSb respectively, in the NaCl structure-in
good agreement with experiment-whilst at the transition pressure, in the CsCl
structure, a drastically increased value of T c around [Formula: see text] K
([Formula: see text] K at 20 GPa) is found for SnSb, together with a dramatic
increase in the electronic density of states at this pressure. The lowest energy
acoustic phonon branches in each structure also demonstrate some softening
effects, which are well addressed in this work.
PMID- 28691691
TI - Development of a clay based bioink for 3D cell printing for skeletal application.
AB - Three-dimensional printing of cell-laden hydrogels has evolved as a promising
approach on the route to patient-specific or complex tissue-engineered
constructs. However, it is still challenging to print structures with both, high
shape fidelity and cell vitality. Herein, we used a synthetic nanosilicate clay,
called Laponite, to build up scaffolds utilising the extrusion-based method 3D
plotting. By blending with alginate and methylcellulose, a bioink was developed
which allowed easy extrusion, achieving scaffolds with high printing fidelity.
Following extrusion, approximately 70%-75% of printed immortalised human
mesenchymal stem cells survived and cell viability was maintained over 21 days
within the plotted constructs. Mechanical properties of scaffolds comprised of
the composite bioink decreased over time when stored under cell culture
conditions. Nevertheless, shape of the plotted constructs was preserved even over
longer cultivation periods. Laponite is known for its favourable drug delivery
properties. Two model proteins, bovine serum albumin and vascular endothelial
growth factor were loaded into the bioink. We demonstrate that the release of
both growth factors significantly changed to a more sustained profile by
inclusion of Laponite in comparison to an alginate-methylcellulose blend in the
absence of Laponite. In summary, addition of a synthetic clay, Laponite, improved
printability, increased shape fidelity and was beneficial for controlled release
of biologically active agents such as growth factors.
PMID- 28691692
TI - Optical and structural characterisation of epitaxial nanoporous GaN grown by CVD.
AB - In this paper we study the optical properties of nanoporous gallium nitride (GaN)
epitaxial layers grown by chemical vapour deposition on non-porous GaN
substrates, using photoluminescence, cathodoluminescence, and resonant Raman
scattering, and correlate them with the structural characteristic of these films.
We pay special attention to the analysis of the residual strain of the layers and
the influence of the porosity in the light extraction. The nanoporous GaN
epitaxial layers are under tensile strain, although the strain is progressively
reduced as the deposition time and the thickness of the porous layer increases,
becoming nearly strain free for a thickness of 1.7 MUm. The analysis of the
experimental data point to the existence of vacancy complexes as the main source
of the tensile strain.
PMID- 28691693
TI - Influence of physico-mechanical properties of elastomeric material for different
cell growth.
AB - The tunable mechanical and physical properties of polydimethylsiloxane (PDMS) are
commonly utilized for studying cellular dynamics. However, the inherent
hydrophobic nature of PDMS limits its application as a cell culture film. Various
surface modification techniques render PDMS films hydrophilic, altering their
surface chemistry, elasticity, roughness and the cell attachment of anchorage
dependent cell types to the films. The surface properties of thin films lead to
the alteration of the biomechano-physical properties of cells, so they can be
used as a mechanical signature for the viability testing of different types of
cell, such as normal and cancerous ones. In this study, 3T3 fibroblast and HaCaT
keratinocyte cells were grown on different pristine and oxidized PDMS
compositions by varying their base-to-curing-agent ratios (w/w). The enhanced
wettability favors the cell spreading and growth rate of both 3T3 and HaCaT
cells, and it varies with the film's surface chemistry and elasticity. This study
focuses on the importance of understanding how various surface modification
methods, like oxygen plasma and piranha treatment, can impact cell-cell and cell
substrate interaction for different cell types, thereby assisting in the
preparation of various PDMS-based biomedical devices.
PMID- 28691694
TI - Context-dependent adaptation improves robustness of myoelectric control for upper
limb prostheses.
AB - OBJECTIVE: Dexterous upper-limb prostheses are available today to restore
grasping, but an effective and reliable feed-forward control is still missing.
The aim of this work was to improve the robustness and reliability of myoelectric
control by using context information from sensors embedded within the prosthesis.
APPROACH: We developed a context-driven myoelectric control scheme (cxMYO) that
incorporates the inference of context information from proprioception (inertial
measurement unit) and exteroception (force and grip aperture) sensors to modulate
the outputs of myoelectric control. Further, a realistic evaluation of the cxMYO
was performed online in able-bodied subjects using three functional tasks, during
which the cxMYO was compared to a purely machine-learning-based myoelectric
control (MYO). MAIN RESULTS: The results demonstrated that utilizing context
information decreased the number of unwanted commands, improving the performance
(success rate and dropped objects) in all three functional tasks. Specifically,
the median number of objects dropped per round with cxMYO was zero in all three
tasks and a significant increase in the number of successful transfers was seen
in two out of three functional tasks. Additionally, the subjects reported better
user experience. SIGNIFICANCE: This is the first online evaluation of a method
integrating information from multiple on-board prosthesis sensors to modulate the
output of a machine-learning-based myoelectric controller. The proposed scheme is
general and presents a simple, non-invasive and cost-effective approach for
improving the robustness of myoelectric control.
PMID- 28691695
TI - Mechanical and biological characterization of alkaline substituted orthophosphate
bone substitutes containing meta- and diphosphates.
AB - Despite the growing knowledge on the mechanisms of fracture healing, bone defects
often do not heal in a timely manner. Clinically, tricalcium phosphate (TCP) bone
substitutes are used to fill bone defects and promote bone healing. However, the
degradation rate of these implants is often too slow for sufficient bone
replacement. The use of calcium phosphate material with the crystalline phase
Ca10[K/Na](PO4)7 containing different amounts of di- and metaphosphates may
overcome this problem, because these materials show an accelerated degradation.
Therefore, we generated alkaline substituted Ca-P scaffolds with different
amounts of ortho-, di- and metaphosphates. The degradation of these materials was
analyzed in TRIS-HCl buffer solution in vitro. Moreover, we measured the
compressive strength and porosity of the scaffolds by micro-CT analysis. The
biocompatibility of the scaffolds was evaluated in vivo in the mouse dorsal
skinfold chamber by means of intravital fluorescence microscopy and histology. We
found that higher amounts of incorporated di- and metaphosphates increase the
degradation rate and compressive strength of the scaffolds without inducing a
stronger leukocytic inflammatory host tissue reaction after implantation.
Histological analyses confirmed the good biocompatibility of the scaffolds
containing di- and metaphosphates. In summary, this study demonstrates that the
compressive strength and degradation rate of Ca-P scaffolds can be improved by
incorporation of di- and metaphosphates without affecting their good
biocompatibility. Hence, this material modification may be particularly
beneficial for the treatment of metaphyseal bone defects in weight bearing
locations.
PMID- 28691696
TI - Decellularized extracellular matrix: a step towards the next generation source
for bioink manufacturing.
AB - In tissue engineering, the need for hierarchical assembly of three-dimensional
(3D) tissues has become increasingly important, considering that new technology
is essential for advanced tissue fabrication. 3D cell printing has emerged as a
powerful technology to recapitulate the microenvironment of native tissue,
allowing for the precise deposition of multiple cells onto the pre-defined
position. Parallel to these technological advances, the search for an appropriate
bioink that can provide a suitable microenvironment supporting cellular
activities has been in the spotlight. In this respect, the decellularized
extracellular matrix (dECM) becomes a popular candidate as a well-qualified
source of bioink because of its capability to inherit the intrinsic cues from a
native ECM. Yet, few studies have been reported and its potential has been
partially understood in the field of 3D cell printing. In this review, our focus
is on a dECM as a prospective bioink to facilitate 3D cell printing-based tissue
engineering. We begin this review with a brief description of the important role
of the ECM. Next, the representative methods of decellularization and
conventional applications of a dECM are introduced, followed by the recent
achievements in dECM bioinks and their future directions.
PMID- 28691697
TI - Wafer-scale single-crystal perovskite patterned thin films based on geometrically
confined lateral crystal growth.
AB - We report a facile roll-printing method, geometrically confined lateral crystal
growth, for the fabrication of large-scale, single-crystal CH3NH3PbI3 perovskite
thin films. Geometrically confined lateral crystal growth is based on transfer of
a perovskite ink solution via a patterned rolling mould to a heated substrate,
where the solution crystallizes instantly with the immediate evaporation of the
solvent. The striking feature of this method is that the instant crystallization
of the feeding solution under geometrical confinement leads to the unidirectional
lateral growth of single-crystal perovskites. Here, we fabricated single-crystal
perovskites in the form of a patterned thin film (3 * 3 inch) with a high carrier
mobility of 45.64 cm2 V-1 s-1. We also used these single-crystal perovskite thin
films to construct solar cells with a lateral configuration. Their active-area
power conversion efficiency shows a highest value of 4.83%, which exceeds the
literature efficiency values of lateral perovskite solar cells.
PMID- 28691698
TI - Rising to the challenge of surging seas.
PMID- 28691699
TI - Ancient hydrothermal seafloor deposits in Eridania basin on Mars.
AB - The Eridania region in the southern highlands of Mars once contained a vast
inland sea with a volume of water greater than that of all other Martian lakes
combined. Here we show that the most ancient materials within Eridania are thick
(>400 m), massive (not bedded), mottled deposits containing saponite, talc
saponite, Fe-rich mica (for example, glauconite-nontronite), Fe- and Mg
serpentine, Mg-Fe-Ca-carbonate and probable Fe-sulphide that likely formed in a
deep water (500-1,500 m) hydrothermal setting. The Eridania basin occurs within
some of the most ancient terrain on Mars where striking evidence for remnant
magnetism might suggest an early phase of crustal spreading. The relatively well
preserved seafloor hydrothermal deposits in Eridania are contemporaneous with the
earliest evidence for life on Earth in potentially similar environments 3.8
billion years ago, and might provide an invaluable window into the environmental
conditions of early Earth.
PMID- 28691700
TI - Exploring the hidden interior of the Earth with directional neutrino
measurements.
AB - Roughly 40% of the Earth's total heat flow is powered by radioactive decays in
the crust and mantle. Geo-neutrinos produced by these decays provide important
clues about the origin, formation and thermal evolution of our planet, as well as
the composition of its interior. Previous measurements of geo-neutrinos have all
relied on the detection of inverse beta decay reactions, which are insensitive to
the contribution from potassium and do not provide model-independent information
about the spatial distribution of geo-neutrino sources within the Earth. Here we
present a method for measuring previously unresolved components of Earth's
radiogenic heating using neutrino-electron elastic scattering and low-background,
direction-sensitive tracking detectors. We calculate the exposures needed to
probe various contributions to the total geo-neutrino flux, specifically those
associated to potassium, the mantle and the core. The measurements proposed here
chart a course for pioneering exploration of the veiled inner workings of the
Earth.
PMID- 28691701
TI - Instructing cells with programmable peptide DNA hybrids.
AB - The native extracellular matrix is a space in which signals can be displayed
dynamically and reversibly, positioned with nanoscale precision, and combined
synergistically to control cell function. Here we describe a molecular system
that can be programmed to control these three characteristics. In this approach
we immobilize peptide-DNA (P-DNA) molecules on a surface through complementary
DNA tethers directing cells to adhere and spread reversibly over multiple cycles.
The DNA can also serve as a molecular ruler to control the distance-dependent
synergy between two peptides. Finally, we use two orthogonal DNA handles to
regulate two different bioactive signals, with the ability to independently up-
or downregulate each over time. This enabled us to discover that neural stem
cells, derived from the murine spinal cord and organized as neurospheres, can be
triggered to migrate out in response to an exogenous signal but then regroup into
a neurosphere as the signal is removed.
PMID- 28691702
TI - Corrigendum: Genetic interactions and functional analyses of the fission yeast
gsk3 and amk2 single and double mutants defective in TORC1-dependent processes.
AB - This corrects the article DOI: 10.1038/srep44257.
PMID- 28691703
TI - Corrigendum: The effects of three-dimensional defects on one-way surface plasmon
propagation for photonic topological insulators comprised of continuum media.
AB - This corrects the article DOI: 10.1038/srep30055.
PMID- 28691705
TI - Corrigendum: Study on the noncoincidence effect phenomenon using matrix isolated
Raman spectra and the proposed structural organization model of acetone in
condense phase.
AB - This corrects the article DOI: 10.1038/srep43835.
PMID- 28691704
TI - The self-inhibitory nature of metabolic networks and its alleviation through
compartmentalization.
AB - Metabolites can inhibit the enzymes that generate them. To explore the general
nature of metabolic self-inhibition, we surveyed enzymological data accrued from
a century of experimentation and generated a genome-scale enzyme-inhibition
network. Enzyme inhibition is often driven by essential metabolites, affects the
majority of biochemical processes, and is executed by a structured network whose
topological organization is reflecting chemical similarities that exist between
metabolites. Most inhibitory interactions are competitive, emerge in the close
neighbourhood of the inhibited enzymes, and result from structural similarities
between substrate and inhibitors. Structural constraints also explain one-third
of allosteric inhibitors, a finding rationalized by crystallographic analysis of
allosterically inhibited L-lactate dehydrogenase. Our findings suggest that the
primary cause of metabolic enzyme inhibition is not the evolution of regulatory
metabolite-enzyme interactions, but a finite structural diversity prevalent
within the metabolome. In eukaryotes, compartmentalization minimizes inevitable
enzyme inhibition and alleviates constraints that self-inhibition places on
metabolism.
PMID- 28691706
TI - Crosstalk and the evolvability of intracellular communication.
AB - Metazoan signalling networks are complex, with extensive crosstalk between
pathways. It is unclear what pressures drove the evolution of this architecture.
We explore the hypothesis that crosstalk allows different cell types, each
expressing a specific subset of signalling proteins, to activate different
outputs when faced with the same inputs, responding differently to the same
environment. We find that the pressure to generate diversity leads to the
evolution of networks with extensive crosstalk. Using available data, we find
that human tissues exhibit higher levels of diversity between cell types than
networks with random expression patterns or networks with no crosstalk. We also
find that crosstalk and differential expression can influence drug activity: no
protein has the same impact on two tissues when inhibited. In addition to
providing a possible explanation for the evolution of crosstalk, our work
indicates that consideration of cellular context will likely be crucial for
targeting signalling networks.
PMID- 28691707
TI - Controlled spatial separation of spins and coherent dynamics in spin-orbit
coupled nanostructures.
AB - The spatial separation of electron spins followed by the control of their
individual spin dynamics has recently emerged as an essential ingredient in many
proposals for spin-based technologies because it would enable both of the two
spin species to be simultaneously utilized, distinct from most of the current
spintronic studies and technologies wherein only one spin species could be
handled at a time. Here we demonstrate that the spatial spin splitting of a
coherent beam of electrons can be achieved and controlled using the interplay
between an external magnetic field and Rashba spin-orbit interaction in
semiconductor nanostructures. The technique of transverse magnetic focusing is
used to detect this spin separation. More notably, our ability to engineer the
spin-orbit interactions enables us to simultaneously manipulate and probe the
coherent spin dynamics of both spin species and hence their correlation, which
could open a route towards spintronics and spin-based quantum information
processing.
PMID- 28691709
TI - Corrigendum: Photon-phonon Interaction in a Microfiber Induced by Optical and
Electrostrictive Forces.
AB - This corrects the article DOI: 10.1038/srep41849.
PMID- 28691708
TI - An exported protein-interacting complex involved in the trafficking of virulence
determinants in Plasmodium-infected erythrocytes.
AB - The malaria parasite, Plasmodium falciparum, displays the P. falciparum
erythrocyte membrane protein 1 (PfEMP1) on the surface of infected red blood
cells (RBCs). We here examine the physical organization of PfEMP1 trafficking
intermediates in infected RBCs and determine interacting partners using an
epitope-tagged minimal construct (PfEMP1B). We show that parasitophorous vacuole
(PV)-located PfEMP1B interacts with components of the PTEX (Plasmodium Translocon
of EXported proteins) as well as a novel protein complex, EPIC (Exported Protein
Interacting Complex). Within the RBC cytoplasm PfEMP1B interacts with components
of the Maurer's clefts and the RBC chaperonin complex. We define the EPIC
interactome and, using an inducible knockdown approach, show that depletion of
one of its components, the parasitophorous vacuolar protein-1 (PV1), results in
altered knob morphology, reduced cell rigidity and decreased binding to CD36.
Accordingly, we show that deletion of the Plasmodium berghei homologue of PV1 is
associated with attenuation of parasite virulence in vivo.
PMID- 28691710
TI - Global mismatch between fishing dependency and larval supply from marine
reserves.
AB - Marine reserves are viewed as flagship tools to protect exploited species and to
contribute to the effective management of coastal fisheries. Yet, the extent to
which marine reserves are globally interconnected and able to effectively seed
areas, where fisheries are most critical for food and livelihood security is
largely unknown. Using a hydrodynamic model of larval dispersal, we predict that
most marine reserves are not interconnected by currents and that their potential
benefits to fishing areas are presently limited, since countries with high
dependency on coastal fisheries receive very little larval supply from marine
reserves. This global mismatch could be reversed, however, by placing new marine
reserves in areas sufficiently remote to minimize social and economic costs but
sufficiently connected through sea currents to seed the most exploited fisheries
and endangered ecosystems.
PMID- 28691711
TI - Generation and comparison of CRISPR-Cas9 and Cre-mediated genetically engineered
mouse models of sarcoma.
AB - Genetically engineered mouse models that employ site-specific recombinase
technology are important tools for cancer research but can be costly and time
consuming. The CRISPR-Cas9 system has been adapted to generate autochthonous
tumours in mice, but how these tumours compare to tumours generated by
conventional recombinase technology remains to be fully explored. Here we use
CRISPR-Cas9 to generate multiple subtypes of primary sarcomas efficiently in wild
type and genetically engineered mice. These data demonstrate that CRISPR-Cas9 can
be used to generate multiple subtypes of soft tissue sarcomas in mice. Primary
sarcomas generated with CRISPR-Cas9 and Cre recombinase technology had similar
histology, growth kinetics, copy number variation and mutational load as assessed
by whole exome sequencing. These results show that sarcomas generated with CRISPR
Cas9 technology are similar to sarcomas generated with conventional modelling
techniques and suggest that CRISPR-Cas9 can be used to more rapidly generate
genotypically and phenotypically similar cancers.
PMID- 28691712
TI - Erratum: Reduction of Abeta amyloid pathology in APPPS1 transgenic mice in the
absence of gut microbiota.
AB - This corrects the article DOI: 10.1038/srep41802.
PMID- 28691714
TI - Dehydration of subducting slow-spread oceanic lithosphere in the Lesser Antilles.
AB - Subducting slabs carry water into the mantle and are a major gateway in the
global geochemical water cycle. Fluid transport and release can be constrained
with seismological data. Here we use joint active-source/local-earthquake seismic
tomography to derive unprecedented constraints on multi-stage fluid release from
subducting slow-spread oceanic lithosphere. We image the low P-wave velocity
crustal layer on the slab top and show that it disappears beneath 60-100 km
depth, marking the depth of dehydration metamorphism and eclogitization.
Clustering of seismicity at 120-160 km depth suggests that the slab's mantle
dehydrates beneath the volcanic arc, and may be the main source of fluids
triggering arc magma generation. Lateral variations in seismic properties on the
slab surface suggest that serpentinized peridotite exhumed in tectonized slow
spread crust near fracture zones may increase water transport to sub-arc depths.
This results in heterogeneous water release and directly impacts earthquakes
generation and mantle wedge dynamics.
PMID- 28691715
TI - Dichlorodiphenyltrichloroethane (DDT) induced extracellular vesicle formation: a
potential role in organochlorine increased risk of Parkinson's disease.
AB - A number of studies have demonstrated that rural living and exposure to
pesticides such as dichlorodiphenyltrichloroethane (DDT) highly increase the
chances of developing Parkinson's disease. In a previous work, we have found that
DDT leads to the formation of vesicular buds that are released from the cells
upon fusion of an intermediate endocytic compartment with the plasma membrane.
Since extracellular vesicles like exosomes have been implicated in the
development of neurodegenerative diseases through the propagation of neurotoxic
misfolded proteins from neuron to neuron, in this minireview we propose that
organochlorine pesticides could enhance the risk of neurodegenerative diseases by
increasing the formation of exosomes.
PMID- 28691713
TI - Targeted therapies for renal cell carcinoma.
AB - The management of patients with metastatic renal cell carcinoma (RCC) has changed
dramatically over the past few years. Nephrectomy remains an important
intervention for localized RCC but systemic therapy is the mainstay of treatment
for patients who relapse after surgery or who have metastatic RCC. Before 2005,
medical therapies for RCC were limited to cytokine therapies, which are very
toxic and benefit only a small percentage of patients. In 2017, therapeutic
agents now include kinase and immune checkpoint inhibitors. Contemporary research
with these agents is now focusing on combinatorial and perioperative therapy. The
field is now faced with the evolving challenge of how to select the best therapy
for each patient during their natural history of disease, which has created a
strong interest in modern sequencing and molecular approaches to identify
biomarkers to personalize treatments. New therapeutic agents and approaches are
associated with different toxicities and financial burdens, which require
consideration of value by measuring clinical benefit, toxicity, and the cost of
each drug with an organized framework. In this Review, we discuss the mechanisms
underlying RCC and how improved molecular understanding helped the development of
therapies, as well as biomarkers of response to treatment. We also discuss the
value of these agents and their impact on personalization of therapy and drug
development for RCC.
PMID- 28691716
TI - Functional organization of the human amygdala in appetitive learning.
AB - The amygdala is a small subcortical structure located bilaterally in medial
temporal lobes. It is a key region for emotional processes and some forms of
associative learning. In particular, the role of the amygdala in processing of
negative emotions and aversive learning has been shown in numerous studies.
However, involvement of this structure in processing of positive affect and
appetitive learning is not fully understood. Previous experiments in animals are
not consistent. While some authors implicate only the centromedial part of the
amygdala in appetitive learning, the others suggest contribution of both
centromedial and basolateral subregions. Although from the evolutionary
perspective appetitive learning is equally important as aversive learning,
research on the role of the human amygdala and its subregions in appetitive
learning is undertaken relatively rarely and the results are not conclusive.
Therefore, the aim of this review is twofold: to summarize the current knowledge
in this field and to indicate and discuss the factors, which might affect the
observed level of the amygdala activity during appetitive learning in humans.
PMID- 28691717
TI - Interaction between urethane and cannabinoid CB1 receptor agonist and antagonist
in penicillin-induced epileptiform activity.
AB - Previous experimental studies have shown that various anesthetics alter the
effects of cannabinoid agonists and antagonists on the cardiac response to
different stimuli. Since no data have shown an interaction between urethane and
cannabinoid signaling in epilepsy, we examined the suitability of urethane with
regard to testing the effects of a cannabinoid CB1 receptor agonist and an
antagonist on penicillin-induced epileptiform activity in rats. Permanent screw
electrodes for electrocorticographic (ECoG) recordings, and a permanent cannula
for administration of the substances to the brain ventricles, were placed into
the cranium of rats. Epileptiform activity was induced by injection of penicillin
through the cannula in conscious animal. The CB1 receptor agonist arachidonyl-2
chloroethylamide (ACEA; 7.5 MUg) and the CB1 receptor antagonist [N-(piperidin-1
yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3 carboxamide]
(AM-251; 0.25 MUg) were administered intracerebroventricularly 30 minutes after
the penicillin application in urethane-anesthetized and conscious animals.
Urethane completely eliminated spontaneous ictal events in ECoG recordings and
reduced the frequency and total amount of epileptiform activity. It did not alter
either the proconvulsant effects of AM-251 or the anticonvulsant effects of ACEA
on penicillin-induced epileptiform activity. The electrophysiological evidence
suggests that there is no possible interaction between urethane and cannabinoid
CB1 receptors in this experimental model of epilepsy.
PMID- 28691718
TI - Additive and antagonistic antinociceptive interactions between magnesium sulfate
and ketamine in the rat formalin test.
AB - Because ketamine and magnesium block NMDA receptor activation by distinct
mechanisms of action, we hypothesized that in a model of inflammatory pain in
rats the combination of ketamine and magnesium might be more effective than
ketamine alone. Antinociceptive activity was assessed by the formalin test in
male Wistar rats (200-250 g). Animals were injected with 100 MUL of 2.5% formalin
to the plantar surface of the right hind paw. Data were recorded as the total
time spent in pain-related behavior after the injection of formalin or vehicle
(0.9% NaCl). Ketamine and magnesium sulfate given separately reduced nocifensive
behavior in the second phase of the formalin test in rats. When ketamine was
applied after magnesium sulfate, the log dose-response curves for the effects of
ketamine and the magnesium sulfate-ketamine combination revealed antagonistic
interaction, and about 1.6 (CL 1.2-2.4) fold increment in ketamine dosage. A low
dose of magnesium sulfate (5 mg/kg, subcutaneously) administered after ketamine
increased the antinociceptive effect of ketamine by a factor of only 1.2 (CL 0.95
1.38), indicating an additive interaction. There was a 1.8-fold reduction in
dosage of ketamine when ketamine was administered before rather than after the
magnesium sulfate. The present study revealed that both ketamine and magnesium
reduced pain-related behavior in the second phase of the formalin test in rats.
Ketamine, when administered before or after the magnesium, provided additive or
antagonistic antinociceptive interactions, respectively. Whether there will be an
additive or antagonistic antinociceptive interaction between ketamine and
magnesium depends on the order of drug administration.
PMID- 28691719
TI - Narcolepsy type 1 and hypersomnia associated with a psychiatric disorder show
different slow wave activity dynamics.
AB - The aim of the study was to compare electrophysiological parameters of night
sleep in narcolepsy type 1 and hypersomnia associated with a psychiatric
disorder. Fortyfour patients: 15 with narcolepsy type 1, 14 with hypersomnia
associated with a psychiatric disorder and 15 age- and sex-matched controls
participated in the study. The study subjects filled in the Athens Insomnia Scale
(AIS) and the Beck Depression Inventory (BDI). The severity of daytime sleepiness
was quantified subjectively using the Epworth Sleepiness Scale (ESS) and the
Stanford Sleepiness Scale (SSS), and objectively using the Multiple Sleep Latency
Test (MSLT). All subjects underwent polysomnography (PSG) on the two consecutive
nights. The data from the second night was analysed. The slow wave activity (SWA,
1-4 Hz) was calculated for the three consecutive sleep cycles, and topographic
delta power maps were plotted. In contrast to narcoleptics, psychiatric
hypersomniacs had undisturbed nocturnal sleep, high sleep efficiency, normal non
rapid eye movement (NREM) and rapid eye movement (REM) sleep proportions, normal
REM latency and sleep latencies on MSLT and PSG. The subjective and objective
sleepiness was significantly higher in narcolepsy group than in psychiatric
hypersomnia group. In all the study groups SWA was the most prominent in frontal
areas, while the greatest between-group differences were found in the central
areas. There were significant differences between the groups in SWA in the second
NREM episode. The highest SWA was observed in the hypersomnia group, while the
lowest in the narcolepsy group. Psychiatric hypersomniacs and controls did not
differ in the SWA exponential decline over consecutive NREM episodes, whereas
narcoleptics exhibited a steeper dissipation of sleep pressure from the first to
the second NREM episode. In conclusion, narcolepsy type1 and hypersomnia
associated with psychiatric disorder differ in the SWA dynamics. Narcoleptics
presented with the altered dynamics of sleep homeostasis, whereas psychiatric
hypersomniacs showed normal nocturnal sleep and normal sleep homeostasis.
PMID- 28691720
TI - An effect of continuous contextual filling in the filled-space illusion.
AB - In the filled-space (or Oppel-Kundt) illusion, the filled part of the stimulus
for most observers appears longer in comparison with the empty one. In the first
two experimental series of the present study, we investigated the illusory effect
as a function of continuous filling (by a shaft-line segment) of the reference
spatial interval of the three-dot stimulus. It was demonstrated that for the
fixed length of the reference interval, the magnitude of the illusion increases
non-linearly with the shaft length. For the fixed length of the shaft, the
illusion magnitude gradually decreases with the lengthening of the reference
interval. In the third series, psychophysical examination of the conventional
Oppel-Kundt stimulus with different number of equally spaced elements (dots)
subdividing its filled part was performed. Based on the analysis of the
functional dependencies established, we have proposed a simple computational
model that was successfully applied to fit the experimental data obtained in the
present study.
PMID- 28691721
TI - Nonlinear dynamics analysis of the human balance control subjected to physical
and sensory perturbations.
AB - Postural control after applying perturbation involves neural and muscular efforts
to limit the center of mass (CoM) motion. Linear dynamical approaches may not
unveil all complexities of body efforts. This study was aimed at determining two
nonlinear dynamics parameters (fractal dimension (FD) and largest Lyapunov
exponent (LLE)) in addition to the linear standing metrics of balance in
perturbed stance. Sixteen healthy young males were subjected to sudden rotations
of the standing platform. The vision and cognition during the standing were also
interfered. Motion capturing was used to measure the lower limb joints and the
CoM displacements. The CoM path length as a linear parameter was increased by
elimination of vision (p<0.01) and adding a cognitive load (p<0.01). The CoM
nonlinear metric FD was decreased due to the cognitive loads (p<0.001). The
visual interference increased the FD of all joints when the task included the
cognitive loads (p<0.01). The slightly positive LLE values showed weakly-chaotic
behavior of the whole body. The local joint rotations indicated higher LLEs.
Results indicated weakly chaotic response of the whole body. Increase in the task
difficulty by adding sensory interference had difference effects on parameters.
Linear and nonlinear metrics of the perturbed stance showed that a combination of
them may properly represent the body behavior.
PMID- 28691722
TI - Potential role of dopamine transporter in behavioral flexibility.
AB - Behavioral flexibility is subserved by the prefrontal cortex and the basal
ganglia. Orbitofrontal cortex (OFC) and dorsomedial striatum (DMS) form a
functional frontocorticostriatal circuit crucial for the mediation of flexibility
during reversal learning via dopamine (DA) neurotransmission. The regulatory
control in maintaining DA homeostasis and function is provided by the dopamine
transporter (DAT), which therefore likely plays a significant role in controlling
the influence of DA on cognitive processes. Here we used a gene knockout mouse
model to investigate the role of DAT in the performance on the Attentional Set
Shifting Task (ASST) stages dependent upon the OFC and the DMS. Additionally,
behavior of mice after repeated administration of selective DAT inhibitor, GBR
12909, was examined. The animals were treated with the inhibitor to elicit a
compensatory DAT up-regulation following withdrawal. Learning was slower and the
number of errors during reversal learning and intra-dimensional shift stages was
higher in DAT+/- mutant mice than in WT mice. GBR 12909-treated mice had deficits
in reversal stages of the ASST. Neuronal activation in the OFC and DMS during the
ASST was examined with early growth response proteins 1 and 2 (egr-1, egr-2)
immunohistochemistry. Density of egr-2 labeled cells in the OFC was lower in
mutant mice than in wild-types during reversal learning and the expression of the
egr-1 was lower in mutant mice in the OFC and DMS during reversal and intra
dimensional shift stages. Mice with decreased DAT levels displayed behavioral
difficulties that were accompanied by a lower task-induced activation of neurons
in brain regions involved in the reversal learning. Altogether, these data
indicate the role of the DAT in the behavioral flexibility.
PMID- 28691723
TI - Effect of ethanol on the visual-evoked potential in rat: dynamics of ON and OFF
responses.
AB - The effect of acute ethanol administration on the flash visual-evoked potential
(VEP) was investigated in numerous studies. However, it is still unclear which
brain structures are responsible for the differences observed in stimulus onset
(ON) and offset (OFF) responses and how these responses are modulated by ethanol.
The aim of our study was to investigate the pattern of ON and OFF responses in
the visual system, measured as amplitude and latency of each VEP component
following acute administration of ethanol. VEPs were recorded at the onset and
offset of a 500 ms visual stimulus in anesthetized male Wistar rats. The effect
of alcohol on VEP latency and amplitude was measured for one hour after injection
of 2 g/kg ethanol dose. Three VEP components - N63, P89 and N143 - were analyzed.
Our results showed that, except for component N143, ethanol increased the latency
of both ON and OFF responses in a similar manner. The latency of N143 during OFF
response was not affected by ethanol but its amplitude was reduced. Our study
demonstrated that the activation of the visual system during the ON response to a
500 ms visual stimulus is qualitatively different from that during the OFF
response. Ethanol interfered with processing of the stimulus duration at the
level of the visual cortex and reduced the activation of cortical regions.
PMID- 28691724
TI - Gas phase hydration of halogenated benzene cations. Is it hydrogen or halogen
bonding?
AB - Halogen bonding (XB) non-covalent interactions can be observed in compounds
containing chlorine, bromine, or iodine which can form directed close contacts of
the type R1-XY-R2, where the halogen X acts as a Lewis acid and Y can be any
electron donor moiety including electron lone pairs on hetero atoms such as O and
N, or pi electrons in olefin double bonds and aromatic conjugated systems. In
this work, we present the first evidence for the formation of ionic halogen bonds
(IXBs) in the hydration of bromobenzene and iodobenzene radical cations in the
gas phase. We present a combined thermochemical investigation using the mass
selected ion mobility (MSIM) technique and density functional theory (DFT)
calculations of the stepwise hydration of the fluoro, chloro, bromo, and
iodobenzene radical cations. The binding energy associated with the formation of
an IXB in the hydration of the iodobenzene cation (11.2 kcal mol-1) is about 20%
higher than the typical unconventional ionic hydrogen bond (IHB) of the
CHdelta+OH2 interaction. The formation of an IXB in the hydration of the
iodobenzene cation involves a significant entropy loss (29 cal mol-1 K-1)
resulting from the formation of a more ordered structure and a highly directional
interaction between the oxygen lone pair of electrons of water and the
electropositive region around the iodine atom of the iodobenzene cation. In
comparison, the hydration of the fluorobenzene and chlorobenzene cations where
IHBs are formed, -DeltaS degrees = 18-21 cal mol-1 K-1 consistent with the
formation of less ordered structures and loose interactions. The electrostatic
potentials on the lowest energy structures of the hydrated halogenated benzene
radical cations show clearly that the formation of an IXB is driven by a
positively charged sigma-hole on the external side of the halogen atom X along
the C-X bond axis. The size of the sigma-hole increases significantly in
bromobenzene and iodobenzene radical cations which results in strong interaction
potentials with the electron lone pairs of the oxygen atom of the water molecules
and thus IXBs provide the most stable hydrated structures of the bromobenzene and
iodobenzene radical cations. The results clearly distinguish the hydration
behaviors resulting from the ionic hydrogen and halogen bonding interactions of
fluorobenzene and iodobenzene cations, respectively, and establish the different
bonding and structural features of the two interactions.
PMID- 28691725
TI - Programmable, reversible and repeatable wrinkling of shape memory polymer thin
films on elastomeric substrates for smart adhesion.
AB - Programmable, reversible and repeatable wrinkling of shape memory polymer (SMP)
thin films on elastomeric polydimethylsiloxane (PDMS) substrates is realized, by
utilizing the heat responsive shape memory effect of SMPs. The dependencies of
wrinkle wavelength and amplitude on program strain and SMP film thickness are
shown to agree with the established nonlinear buckling theory. The wrinkling is
reversible, as the wrinkled SMP thin film can be recovered to the flat state by
heating up the bilayer system. The programming cycle between wrinkle and flat is
repeatable, and different program strains can be used in different programming
cycles to induce different surface morphologies. Enabled by the programmable,
reversible and repeatable SMP film wrinkling on PDMS, smart, programmable surface
adhesion with large tuning range is demonstrated.
PMID- 28691726
TI - Synthesis, structure and applications of graphene-based 2D heterostructures.
AB - With the profuse amount of two-dimensional (2D) materials discovered and the
improvements in their synthesis and handling, the field of 2D heterostructures
has gained increased interest in recent years. Such heterostructures not only
overcome the inherent limitations of each of the materials, but also allow the
realization of novel properties by their proper combination. The physical and
mechanical properties of graphene mean it has a prominent place in the area of 2D
heterostructures. In this review, we will discuss the evolution and current state
in the synthesis and applications of graphene-based 2D heterostructures. In
addition to stacked and in-plane heterostructures with other 2D materials and
their potential applications, we will also cover heterostructures realized with
lower dimensionality materials, along with intercalation in few-layer graphene as
a special case of a heterostructure. Finally, graphene heterostructures produced
using liquid phase exfoliation techniques and their applications to energy
storage will be reviewed.
PMID- 28691727
TI - Identification and assessment of ecotoxicological hazards attributable to
pollutants in urban wet weather discharges.
AB - Urbanization has led to considerable pressure on urban/suburban aquatic
ecosystems. Urban Wet Weather Discharges (UWWD) during rainfall events are a
major source of pollutants leached onto and into urban surfaces and sewers, which
in turn affect aquatic ecosystems. We assessed the ecotoxicity of the different
compounds identified in UWWD and identified the hazard represented by each of
them. To this end, hazard quotient (HQ) values were calculated for each compound
detected in UWWD based on their predicted no effect concentration (PNEC) values
and their maximum measured effluent concentrations (MECmax) found in the
dissolved part of UWWD. For the 207 compounds identified in UWWD, sufficient data
existed for 165 of them to calculate their PNEC. The ecotoxicity of these
compounds varied greatly. Pesticides represented a high proportion of the wide
variety of hazardous compounds whose HQ values were calculated (94 HQ values),
and they were among the most hazardous pollutants (HQ > 1000) transported by
stormwater. The hazard of combined sewer overflows (CSO) was linked mainly to
heavy metals and pharmaceutical compounds. Consequently, the monitoring of these
pollutants should be a priority in the future. The hazard level of certain
pollutants could have been underestimated due to their adsorption onto particles,
leading to their low concentration in the dissolved phase of UWWD. Hence, an in
depth study of these pollutants will be required to clarify their effects on
aquatic organisms.
PMID- 28691728
TI - Intervention to diminish dehydration and kidney damage among sugarcane workers.
AB - Objective The aim of this study was to assess the potential to reduce kidney
function damage during the implementation of a water, rest, shade (WRS) and
efficiency intervention program among sugarcane workers. Methods A WRS
intervention program adapted from the US Occupational Safety and Health
Administration (OSHA) coupled with an efficiency program began two months into
the 5-month harvest. One of the two groups of workers studied was provided with
portable water reservoirs, mobile shaded tents, and scheduled rest periods.
Health data (anthropometric and questionnaires), blood, and urine were collected
at baseline and at three subsequent times over the course of the harvest. Daily
wet bulb globe temperatures (WBGT) were recorded. Results Across a working day
there were changes in biomarkers indicating dehydration (urine osmolality) and
serum albumin and reduced estimated glomerular filtration rate (eGFR). Cross
shift eGFR decrease was present in both groups; -10.5 mL/min/1.73m2 [95%
confidence interval (95% CI) -11.8- -9.1], but smaller for the intervention group
after receiving the program. Decreased eGFR over the 5-month harvest was seen in
both groups: in the one receiving the intervention -3.4 mL/min/1.73m 2(95% CI
5.5- -1.3) and in the other -5.3 (95% CI -7.9- -2.7). The decrease appeared to
halt after the introduction of the intervention in the group receiving the
program. Conclusion A WRS and efficiency intervention program was successfully
introduced for workers in sugarcane fields and appears to reduce the impact of
heat stress on acute and over-harvest biomarkers of kidney function. Further
research is needed to determine whether biomarker changes predict reduced risk of
chronic kidney disease in this type of work.
PMID- 28691729
TI - In vitro differentiation of primordial germ cells and oocyte-like cells from stem
cells.
AB - Infertility is the result of failure due to an organic disorder of the
reproductive organs, especially their gametes. Recently, much progress has been
made on generating germ cells, including oocytes, from various types of stem
cells. This review focuses on advances in female germ cell differentiation from
different kinds of stem cells, with emphasis on embryonic stem cells, adult stem
cells, and induced pluripotent stem cells. The advantages and disadvantages of
the derivation of female germ cells from several types of stem cells are also
highlighted, as well as the ability of stem cells to generate mature and
functional female gametes. This review shows that stem cell therapies have opened
new frontiers in medicine, especially in the reproductive area, with the
possibility of regenerating fertility.
PMID- 28691730
TI - Effects of colocynth alkaloids and glycosides on Wistar rats fed high-fat diet. A
biochemical and morphological study.
AB - INTRODUCTION: In traditional medicine, Citrullus colocynthis is used to treat
diabetes, hyperlipidemia, cardiovascular diseases, inflammation, and oxidative
stress, all of which can appear when a diet rich in vegetable fats, such as palm
oil, is continuously consumed. Such high-fat diets are chronic stressors of the
hypothalamic-pituitary-adrenal axis. The objective of our study was to analyze
and evaluate the effects of colocynth total alkaloids and glycosides on
metabolic, hormonal, and structural disorders of the adrenal medulla in Wistar
rats fed a high-fat diet. MATERIAL AND METHODS: Twenty six Wistar rats were
distributed as follows: six control animals received a standard laboratory diet;
twenty experimental rats received the standard laboratory diet supplemented with
palm oil - the high-fat diet (HFD). After seven months of this diet, the HFD
group was subdivided into rats treated for the next 2 months with either alkaloid
extract (HFD-ALk group) or ethanol extract of glycosides (HFD-GLc) or animals on
HFD only. Plasma metabolites and ACTH concentrations were measured by standard
methods. Sections of adrenal medulla were stained by Heidenhain-Azan method and
Sudan Black. RESULTS: The adrenal medulla of the HFD rats showed prominent
structural changes, such as hypertrophy of chromaffin and ganglion cells,
vacuolation, inflammatory foci, and fibrosis. The biochemical and hormonal
parameters were significantly improved in the HFD rats treated with alkaloid and
glycoside extracts of Citrullus colocynthis. Moreover, the morphological changes
of the adrenal medulla were attenuated in HFD-ALk and HFD-Glc rats. CONCLUSIONS:
The results of the study indicate that phytotherapy using Citrullus colocynthis
alkaloids may correct metabolic and hormonal perturbations as well as adrenal
medulla structure of rats maintained on HFD.
PMID- 28691731
TI - Trends in receipt of single and repeat courses of antenatal corticosteroid
administration among preterm and term births: A retrospective cohort study.
AB - AIM: To investigate trends in receipt and timing of antenatal corticosteroid
(ACS) administration over a ten-year interval. METHODS: Retrospective cohort
study of all live births from 2006 to 2015 occurring at a tertiary level teaching
hospital in Adelaide, Australia. We analysed temporal trends in the receipt of
single courses and repeat doses of ACSs, according to administration timing prior
to birth. The main outcome measures were receipt of a single course of ACS and
whether administration was 'Optimal' (>=24 h to =7 days) according to timing prior to birth, as well as administration of
repeat doses. RESULTS: Among 47 105 live births, 4191 (8.9%) received any ACS,
while 1009 (2.1%) received at least one repeat dose. From 2006/7 to 2014/15,
receipt of a single course (relative risk (RR) 1.33; 95%CI 1.21, 1.47) or repeat
dose of ACS (RR 1.24; 95%CI 1.01, 1.55) increased. Among women giving birth
between 23-34 weeks gestation, receipt of any ACS increased from 75 to 84%, while
an optimally timed single course of ACS increased from 20.4 to 31.0% (RR 1.40;
95%CI 1.24, 1.87). From 2006/7 to 2014/15, the greatest increase in ACS
administration was evident among infants born 35-36 and >=37 weeks gestation by
caesarean section (RR 1.94; 95%CI 1.48, 2.55 and RR 2.55; 95%CI 1.86, 3.50,
respectively). CONCLUSIONS: While frequently used, less than half of ACS
administration prior to preterm birth was optimally timed. The impact of
suboptimal ACS timing on neonatal outcomes requires further investigation.
PMID- 28691732
TI - Prereader to beginning reader: changes induced by reading acquisition in print
and speech brain networks.
AB - BACKGROUND: Literacy acquisition is a demanding process that induces significant
changes in the brain, especially in the spoken and written language networks.
Nevertheless, large-scale paediatric fMRI studies are still limited. METHODS: We
analyzed fMRI data to show how individual differences in reading performance
correlate with brain activation for speech and print in 111 children attending
kindergarten or first grade and examined group differences between a matched
subset of emergent-readers and prereaders. RESULTS: Across the entire cohort,
individual differences analysis revealed that reading skill was positively
correlated with the magnitude of activation difference between words and symbol
strings in left superior temporal, inferior frontal and fusiform gyri. Group
comparisons of the matched subset of pre- and emergent-readers showed higher
activity for emergent-readers in left inferior frontal, precentral, and
postcentral gyri. Individual differences in activation for natural versus vocoded
speech were also positively correlated with reading skill, primarily in the left
temporal cortex. However, in contrast to studies on adult illiterates, group
comparisons revealed higher activity in prereaders compared to readers in the
frontal lobes. Print-speech coactivation was observed only in readers and
individual differences analyses revealed a positive correlation between
convergence and reading skill in the left superior temporal sulcus. CONCLUSIONS:
These results emphasise that a child's brain undergoes several modifications to
both visual and oral language systems in the process of learning to read. They
also suggest that print-speech convergence is a hallmark of acquiring literacy.
PMID- 28691733
TI - Sudden Death Due to Coronary Arteritis.
AB - We report the case of a middle-aged man, without medical history, who suddenly
died at his workplace. The autopsy highlighted a pathological heart
macroscopically, with multiple small white areas on the left myocardium. Coronary
dissection revealed a pseudotumoural fibromyxoid aspect within the anterior
interventricular artery (AIVA) and the left main coronary trunk, including
reduction in their diameter with tight stenosis. Microscopic examination of these
arteries showed fibroinflammatory wall destruction. In the left myocardium, there
were multiple focal ischemic areas at different stages of recovery. Our case is
an illustration of primary ischemic heart disease due to coronary arteritis, with
a pseudotumoural presentation, which was revealed by sudden death. We discuss the
cause of death and the etiological diagnosis preceding coronary arteritis.
PMID- 28691734
TI - Regulating approaches to learning: Testing learning strategy convergences across
a year at university.
AB - BACKGROUND: Contemporary models of student learning within higher education are
often inclusive of processing and regulation strategies. Considerable research
has examined their use over time and their (person-centred) convergence. The
longitudinal stability/variability of learning strategy use, however, is poorly
understood, but essential to supporting student learning across university
experiences. AIMS: Develop and test a person-centred longitudinal model of
learning strategies across the first-year university experience. METHODS:
Japanese university students (n = 933) completed surveys (deep and surface
approaches to learning; self, external, and lack of regulation) at the beginning
and end of their first year. Following invariance and cross-sectional tests,
latent profile transition analysis (LPTA) was undertaken. RESULTS: Initial
difference testing supported small but significant differences for self-/external
regulation. Fit indices supported a four-group model, consistent across both
measurement points. These subgroups were labelled Low Quality (low deep
approaches and self-regulation), Low Quantity (low strategy use generally),
Average (moderate strategy use), and High Quantity (intense use of all
strategies) strategies. The stability of these groups ranged from stable to
variable: Average (93% stayers), Low Quality (90% stayers), High Quantity (72%
stayers), and Low Quantity (40% stayers). The three largest transitions presented
joint shifts in processing/regulation strategy preference across the year, from
adaptive to maladaptive and vice versa. CONCLUSIONS: Person-centred longitudinal
findings presented patterns of learning transitions that different students
experience during their first year at university. Stability/variability of
students' strategy use was linked to the nature of initial subgroup membership.
Findings also indicated strong connections between processing and regulation
strategy changes across first-year university experiences. Implications for
theory and practice are discussed.
PMID- 28691735
TI - Prenatal maternal cortisol measures predict learning and short-term memory
performance in 3- but not 5-month-old infants.
AB - Little is known about relations between maternal prenatal stress and specific
cognitive processes-learning and memory-in infants. A modified crib-mobile task
was employed in a longitudinal design to test relations between maternal prenatal
cortisol, prenatal subjective stress and anxiety, psychosocial variables, and
learning and memory in 3- and 5-month-old infants. Results revealed that maternal
prenatal cortisol was affected by particular psychosocial variables (e.g.,
maternal age, whether or not the infant's grandmother provided childcare,
financial status), but was unrelated to measures of maternal depression, anxiety,
and stress. Although maternal prenatal cortisol was not predictive of learning or
memory performance in 5-month-old infants, higher levels of basal maternal
cortisol and reduced prenatal cortisol response was predictive of some learning
and short-term memory measures in 3-month-old infants. These results suggest an
influence of maternal neuroendocrine functioning on fetal neurological
development, and the importance of separate examination of subjective and
biological measures of stress.
PMID- 28691736
TI - Civic Science for Public Use: Mind in the Making and Vroom.
AB - Mind in the Making and Vroom are partner initiatives that exemplify a unique
"civic science" approach to "bringing developmental science into the world." Mind
in the Making offers families and professionals working with children 0-8 access
to developmental research, by engaging them in an active process of professional
development and community outreach. Vroom is an outreach and communication
initiative that brings "brain building basics" to communities, inviting parents
to participate in the science of early learning through partnerships with trusted
entities. These initiatives use collaborative, iterative processes in
disseminating findings and implications of child development research.
Preliminary evidence shows early promise of these initiatives to help promote
engaged learning and life skills based on executive function in adults and
children.
PMID- 28691738
TI - Examining the impacts of disaster resettlement from a livelihood perspective: a
case study of Qinling Mountains, China.
AB - Disaster resettlement, as a mitigation and preparedness measure, entails
significant economic, physical, and social impacts, which continue to challenge
understanding of recovery from major events, especially regarding the extent of
the context and environmental efforts to rebuild livelihoods. Based on a case
study of Qinling Mountains, China, this research investigates the effects of
disaster resettlement from a livelihoods perspective. Methodologically, it
proposes a framework that combines the pressure-state-response framework and the
sustainable livelihoods approach, and it employs a structural equation model to
examine how specific factors affect disaster resettlement. The results indicate
that conflicts may occur during and after resettlement owing to the difference or
disparity between the concerns of resettled peasants and those of the government.
Consequently, the risks related to livelihoods need to be taken seriously.
Effective risk communication is critical to bridge the gap between different
stakeholders. The paper concludes with some practical and policy recommendations.
PMID- 28691737
TI - Evaluating the antifibrotic potency of galunisertib in a human ex vivo model of
liver fibrosis.
AB - BACKGROUND AND PURPOSE: Liver fibrosis is a major cause of liver-related
mortality and, so far, no effective antifibrotic drug is available. Galunisertib,
a TGF-beta receptor type I kinase inhibitor, is a potential candidate for the
treatment of liver fibrosis. Here, we evaluated the potency of galunisertib in a
human ex vivo model of liver fibrosis. EXPERIMENTAL APPROACH: Antifibrotic
potency and associated mechanisms were studied ex vivo, using both healthy and
cirrhotic human precision-cut liver slices. Fibrosis-related parameters, both
transcriptional and translational level, were assessed after treatment with
galunisertib. KEY RESULTS: Galunisertib showed a prominent antifibrotic potency.
Phosphorylation of SMAD2 was inhibited, while that of SMAD1 remained unchanged.
In healthy and cirrhotic human livers, spontaneous transcription of numerous
genes encoding collagens, including collagen type I, alpha 1, collagen
maturation, non-collageneous extracellular matrix (ECM) components, ECM
remodelling and selected ECM receptors was significantly decreased. The reduction
of fibrosis-related transcription was paralleled by a significant inhibition of
procollagen I C-peptide released by both healthy and cirrhotic human liver
slices. Moreover, galunisertib showed similar antifibrotic potency in human and
rat lives. CONCLUSIONS AND IMPLICATIONS: Galunisertib is a drug that deserves to
be further investigated for the treatment of liver fibrosis. Inhibition of SMAD2
phosphorylation is probably a central mechanism of action. In addition, blocking
the production and maturation of collagens and promoting their degradation are
related to the antifibrotic action of galunisertib.
PMID- 28691739
TI - Nuclear magnetic resonance- and mass spectrometry-based metabolomics to study
maleic acid toxicity from repeated dose exposure in rats.
AB - Maleic acid (MA), a chemical intermediate used in many consumer and industrial
products, was intentionally adulterated in a variety of starch-based foods and
instigated food safety incidents in Asia. We aim to elucidate possible mechanisms
of MA toxicity after repeated exposure by (1) determining the changes of
metabolic profile using 1 H nuclear magnetic resonance spectroscopy and
multivariate analysis, and (2) investigating the occurrence of oxidative stress
using liquid chromatography tandem mass spectrometry by using Sprague-Dawley rat
urine samples. Adult male rats were subjected to a 28 day subchronic study (0, 6,
20 and 60 mg kg-1 ) via oral gavage. Urine was collected twice a day on days 0,
7, 14, 21 and 28; organs underwent histopathological examination. Changes in body
weight and relative kidney weights in medium- and high-dose groups were
significantly different compared to controls. Morphological alterations were
evident in the kidneys and liver. Metabolomic results demonstrated that MA
exposure increases the urinary concentrations of 8-hydroxy-2'-deoxyguanosine, 8
nitroguanine and 8-iso-prostaglandin F2alpha ; levels of acetoacetate, hippurate,
alanine and acetate demonstrated time- and dose-dependent variations in the
treatment groups. Findings suggest that MA consumption escalates oxidative
damage, membrane lipid destruction and disrupt energy metabolism. These
aforementioned changes in biomarkers and endogenous metabolites elucidate and
assist in characterizing the possible mechanisms by which MA induces nephro- and
hepatotoxicity.
PMID- 28691740
TI - Nutritional monitoring of patients post-bariatric surgery: implications for
smartphone applications.
AB - BACKGROUND: Optimal results from bariatric surgery are contingent on patient
commitment to dietary and lifestyle changes and follow-up care. The present study
aimed to investigate the attitudes and use of mobile health (mHealth) smartphone
applications (apps) as a potential tool for maintaining connectivity between
dietitians and patients post-bariatric surgery. METHODS: A cross-sectional online
survey was developed and distributed to a purposeful sample of bariatric
dietitians and bariatric patients in Australia. The survey questions explored
technology penetration (smartphone and app use), communication preferences,
nutrition monitoring methods, professional relationship expectations and reasons
for loss to follow-up. RESULTS: Survey completion rate was 85% (n = 50/59) for
dietitians and 80% (n = 39/49) for patients. Smartphone ownership was 98% and 95%
for dietitians and patients, respectively. Common reasons given for losing
patients to follow-up suggest that a traditional in-clinic practice setting could
be a barrier for some. Most dietitians (n = 48; 91%) prefer to see patients face
to-face in their clinic, whereas patient preferences extended to e-mail and
mobile messaging. Sixty-eight percent of bariatric patients were receptive to two
way communication with dietitians via an app between clinic visits. Both cohorts
recognised the potential for emerging technologies to be used in practice,
although there was no single routinely recommended mHealth app. CONCLUSIONS: The
present study provides the first insight into the use of mobile devices and apps
by post-bariatric patients and the dietitians who support them. A mixture of
traditional methods and smartphone technology is desirable to both dietitians and
patients. The utility and effectiveness of such technologies should be confirmed
in future intervention studies.
PMID- 28691741
TI - Hereditary leiomyomatosis and renal cell cancer syndrome: A novel mutation in the
FH gene.
PMID- 28691742
TI - Relativistic Effect on 1 J(M,C) in Me4 M, Me3 M- , Ph4 M, and Ph3 M- (M=Pb, Sn,
Ge, Si, and/or C): Role of s-Type Lone Pair Orbitals in the Distinct Effect for
the Anionic Species.
AB - Indirect one-bond nuclear spin-spin couplings between M and C [1 J(M,C)] in Me4
M, Me3 M- , Ph4 M, and Ph3 M- (M=Pb, Sn, Ge, Si, C) are analyzed with
consideration of the relativistic effect and by employing Slater-type basis sets.
The evaluated total values 1 JTL (M,C) reproduced the observed values with some
systematic calculation errors. Fermi contact terms 1 JFC (M,C) contribute
predominantly to 1 JTL (M,C) (~99 %). A distinct relativistic effect on 1 J(Pb,C)
is predicted for Me3 Pb- and Ph3 Pb- . The mechanisms for the distinct effect are
elucidated by using the comparison between Me3 Pb- and Me4 Pb as an example. The
contributions to 1 JFC (M,C) [or 1 JSD+FC (M,C), where SD denotes the spin
dipolar term] are decomposed into those of occupied orbitals and occupied-to
unoccupied transitions. The s-type lone-pair orbitals are demonstrated to
contribute to the distinct relativistic effect on 1 J(Pb,C) of Me3 Pb- (and Ph3
Pb- ). The results are in sharp contrast to the cases of 1 J(M,C) for M atoms
lighter than Pb, such as Si, and are explained by the s character of the M-C
bonds. This treatment enables visualization and clear recognition the origin of
the nuclear couplings for the species exhibiting a relativistic effect.
PMID- 28691743
TI - Effectiveness of speech therapy in adults with intellectual disabilities.
AB - BACKGROUND: This study investigated the effect of speech therapy in a
heterogeneous group of adults with intellectual disability. METHOD: Thirty-six
adults with mild and moderate intellectual disabilities (IQs 40-70; age 18-40
years) with reported poor speech intelligibility received tailored training in
articulation and listening skills delivered in two 3-month periods. Pre- to post
changes in speech intelligibility and receptive vocabulary were assessed using
standardized tasks. RESULTS: The results showed a positive effect of treatment on
speech intelligibility and receptive vocabulary, irrespective of severity of
intellectual disability, hearing loss and intellectual disability aetiology.
CONCLUSIONS: Speech therapy for people with intellectual disability can be
effective at adult age and hearing loss should not prevent treatment. Continued
attention to speech can help augment verbal communication skills in this
population.
PMID- 28691744
TI - Dentists' attitudes towards acute pharmacological pain management in children and
adolescents.
AB - AIM: This study aimed to investigate Swedish dentists' attitudes regarding pain
management strategies for treating children and adolescents. It assessed
recommendations for pre- and postoperative analgesics, and use of local
anaesthesia, and whether application of these strategies differs between general
dental practitioners (GDPs) and specialists in paediatric dentistry (SPDs).
DESIGN: We invited all GDPs (n = 807) in southern Sweden (Region Skane), and all
registered SPDs (n = 122) working in Sweden (929 actively practising dentists
under age 65 years) to participate in a postal survey on pain management in
paediatric dental care. RESULTS: The SPDs reported using all types of pain
reducing strategies more frequently than GDPs except local anaesthesia when
extracting a permanent premolar, which SPDs and GDPs used equally often.
Preoperative analgesic use was greater among SPDs than GDPs. GDPs used local
anaesthesia less frequently for filling therapy in primary teeth than in
permanent teeth. CONCLUSIONS: SPDs recommend preoperative analgesics more often
than GDPs do. GDPs seem to underuse local anaesthetics when treating children and
adolescents. SPDs also use pain management strategies more frequently than GDPs.
Among GDPs, pain management is less frequent when treating primary teeth than
permanent teeth.
PMID- 28691745
TI - Prospective evaluation of the Whitt Neonatal Trigger Score in an 'at-risk'
neonatal population.
AB - AIM: The aim of this study was to prospectively evaluate the Whitt Neonatal
Trigger Score (W-NTS), determining optimum threshold scores for consideration of
medical intervention and intensive care unit admission. METHODS: All neonates on
the postnatal ward (PNW) with a set of pre-defined risk factors were scored on
the W-NTS. Neonates were divided into three groups: 'unwell' admitted to neonatal
intensive care unit (NICU); 'well', who remained on the PNW receiving standard
care; and 'intervention', who received antibiotics but did not require admission
to NICU. RESULTS: A total of 3315 scores from 455 neonates were collected. The W
NTS area under the receiver operating characteristic curve (AUC ROC) was 0.968,
with a score of 2 or more predicting NICU admission, with 82.5% sensitivity and
95.0% specificity. Adopting a cut-off score of 2 for admission would
significantly improve speed to admission (11.6 vs. 6.9 h, P 0.037). A score of 0
was strongly predictive of being well enough to remain on the PNW without
intervention (odds ratio 565.6, P < 0.001), and a score of 1 or more predicted
the need for intravenous antibiotics with 100.0% sensitivity and 86.1%
specificity (AUC ROC 0.977). CONCLUSION: The W-NTS observation chart, previously
shown to outperform existing early warning scores, acts well as an adjunct to
clinical assessment on the PNW, with its simplicity allowing for the successful
and safe use by non-paediatric specialists. We recommend that neonates scoring 1
should be reviewed, with a septic screen and commencement of antibiotic therapy
considered, while those scoring 2 or more should be strongly considered for NICU
admission for further management.
PMID- 28691746
TI - A Fully Automatic Method for Comparing Cartridge Case Images.
AB - When a gun is fired, it leaves marks on cartridge cases that are thought to be
unique to the gun. In current practice, firearms examiners inspect cartridge
cases for "sufficient agreement," in which case they conclude that they come from
the same gun, testifying in courts as such. A 2016 President's Council of
Advisors on Science and Technology report questioned the scientific validity of
such analysis (President's Committee of Advisors on Science and Technology,
Washington, DC, Executive Office of the President). One recommendation was to
convert firearms analysis to an objective method. We propose a fully automated,
open-source method for comparing breechface marks on cartridge cases using 2D
optical images. We improve on existing methodology by automating the selection of
marks, and removing the effects of circular symmetry. We propose an empirical
computation of a "random match probability" given a known database, which can be
used to quantify the weight of evidence. We demonstrate an improvement in
accuracy on images from controlled test fires.
PMID- 28691751
TI - Infectious urticaria complicated with intestinal edema.
PMID- 28691750
TI - Human neonatal thymectomy induces altered B-cell responses and autoreactivity.
AB - An association between T-cell lymphopenia and autoimmunity has long been
proposed, but it remains to be elucidated whether T-cell lymphopenia affects B
cell responses to autoantigens. Human neonatal thymectomy (Tx) results in a
decrease in T-cell numbers and we used this model to study the development of
autoreactivity. Two cohorts of neonatally thymectomized individuals were
examined, a cohort of young (1-5 years post-Tx, n = 10-27) and older children
(>10 years, n = 26), and compared to healthy age-matched controls. T-cell and B
cell subsets were assessed and autoantibody profiling performed. Early post-Tx, a
decrease in T-cell numbers (2.75 * 109 /L vs. 0.71 * 109 /L) and an increased
proportion of memory T cells (19.72 vs. 57.43%) were observed. The presence of
autoantibodies was correlated with an increased proportion of memory T cells in
thymectomized children. No differences were seen in percentages of different B
cell subsets between the groups. The autoantigen microarray showed a skewed
autoantibody response after Tx. In the cohort of older individuals,
autoantibodies were present in 62% of the thymectomized children, while they were
found in only 33% of the healthy controls. Overall, our data suggest that
neonatal Tx skews the autoantibody profile. Preferential expansion and
preservation of Treg (regulatory T) cell stability and function, may contribute
to preventing autoimmune disease development after Tx.
PMID- 28691753
TI - Effect of Aging and Surface Interactions on the Diffusion of Endogenous Compounds
in Latent Fingerprints Studied by Mass Spectrometry Imaging.
AB - The ability to determine the age of fingerprints would be immeasurably beneficial
in criminal investigations. We explore the possibility of determining the age of
fingerprints by analyzing various compounds as they diffuse from the ridges to
the valleys of fingerprints using matrix-assisted laser desorption/ionization
mass spectrometry imaging. The diffusion of two classes of endogenous fingerprint
compounds, fatty acids and triacylglycerols (TGs), was studied in fresh and aged
fingerprints on four surfaces. We expected higher molecular weight TGs would
diffuse slower than fatty acids and allow us to determine the age of older
fingerprints. However, we found interactions between endogenous compounds and the
surface have a much stronger impact on diffusion than molecular weight. For
example, diffusion of TGs is faster on hydrophilic plain glass or partially
hydrophilic stainless steel surfaces, than on a hydrophobic Rain-x treated
surface. This result further complicates utilizing a diffusion model to age
fingerprints.
PMID- 28691752
TI - Mineral trioxide aggregate improves healing response of periodontal tissue to
injury in mice.
AB - BACKGROUND AND OBJECTIVE: Mineral trioxide aggregate (MTA) is a biomaterial used
in endodontic procedures as it exerts beneficial effects on regenerative
processes. In this study, we evaluate the effect of MTA on healing of periodontal
ligament (PDL) and surrounding tissue, following injury, in a transgenic mouse
model and on the differentiation of murine mesenchymal progenitor cells in vitro.
MATERIAL AND METHODS: We used an inducible Cre-loxP in vivo fate mapping approach
to examine the effects of MTA on the contributions of descendants of cells
expressing the alphaSMA-CreERT2 transgene (SMA9+ ) to the PDL and alveolar bone
after experimental injury to the root furcation on the maxillary first molars.
Col2.3GFP was used as a marker to identify mature osteoblasts, cementoblasts and
PDL fibroblasts. The effects of MTA were examined 2, 17 and 30 days after injury
and compared histologically with sealing using an adhesive system. The effects of
two dilutions of medium conditioned with MTA on proliferation and differentiation
of mesenchymal progenitor cells derived from bone marrow (BMSC) and periodontal
ligament (PDLC) in vitro were examined using the PrestoBlue viability assay,
alkaline phosphatase and Von Kossa staining. The expression of markers of
differentiation was assessed using real-time PCR. RESULTS: Histological analyses
showed better repair in teeth restored with MTA, as shown by greater expansion of
SMA9+ progenitor cells and Col2.3GFP+ osteoblasts compared with control teeth. We
also observed a positive effect on differentiation of SMA9+ progenitors into
osteoblasts and cementoblasts in the apical region distant from the site of
injury. The in vitro data showed that MTA-conditioned medium reduced cell
viability and osteogenic differentiation in both PDLC and BMSC, indicated by
reduced von Kossa staining and lower expression of osteocalcin and bone
sialoprotein. In addition, cultures grown in the presence of MTA had marked
decreases in SMA9+ and Col2.3GFP+ areas as compared with osteogenic medium,
confirming reduced osteogenesis. CONCLUSION: MTA promotes regeneration of injured
PDL and alveolar bone, reflected as contribution of progenitors (SMA9+ cells)
into osteoblasts (Col2.3GFP+ cells). In vitro, MTA-conditioned medium fails to
promote osteogenic differentiation of both PDLC and BMSC.
PMID- 28691754
TI - Colonic poorly differentiated adenocarcinoma with abundant cancer-associated
fibroblasts diagnosed by trans-gastric endoscopic ultrasound-guided fine needle
aspiration cytology.
PMID- 28691755
TI - Maybe the fountain of youth was actually a treadmill: role of exercise in
reversing microvascular and diastolic dysfunction.
PMID- 28691756
TI - Surgical specimen handover from the operating theatre to laboratory-Can we
improve patient safety by learning from aviation and other high-risk
organisations?
AB - Essential communication between healthcare staff is considered one of the key
requirements for both safety and quality care when patients are handed over from
one clinical area to other. This is particularly important in environments such
as the operating theatre and intensive care where mistakes can be devastating.
Health care has learned from other high-risk organisations (HRO) such as aviation
where the use of checklists and human factors awareness has virtually eliminated
human error and mistakes. To our knowledge, little has been published around ways
to improve pathology specimen handover following surgery, with pathology request
forms often conveying the bare minimum of information to assist the laboratory
staff. Furthermore, the request form might not warn staff about potential
hazards. In this article, we provide a brief summary of the factors involved in
human error and introduce a novel checklist that can be readily completed at the
same time as the routine pathology request form. This additional measure enhances
safety, can help to reduce processing and mislabelling errors and provides
essential information in a structured way assisting both laboratory staff and
pathologists when handling head and neck surgical specimens.
PMID- 28691757
TI - Nursing values: Divided we stand.
PMID- 28691758
TI - Cooperative Activation of Cobalt-Salen Complexes for Epoxide Hydration Promoted
on Flexible Porous Organic Frameworks.
AB - Developing solid catalysts with multiple active sites working cooperatively is
desirable for efficient chemical transformations. However, most solid catalysts
are rigid and impede the cooperation between their spatially isolated active
sites. Two flexible porous organic frameworks (POFs) with integrated Co(salen) as
active sites have been successfully synthesized for mimicking the cooperative
modes of enzymes. The POFs exhibit second-order rate dependence on Co(salen)
concentration in the network and afford much higher TOF (3300 versus 2670 h-1 )
than the homogeneous counterpart in the hydration of propylene epoxide. POFs with
a flexible network thus not only facilitate but also enhance the cooperation of
nearby Co(salen). Moreover, POFs could catalyze oversized substrates, have a wide
substrate scope, and exhibit high stability.
PMID- 28691759
TI - Mortality After Osteoporotic Fractures: What Proportion Is Caused by Fracture and
Is Preventable?
PMID- 28691760
TI - New Challenges in Psycho-Oncology Research III: A systematic review of
psychological interventions for prostate cancer survivors and their partners:
clinical and research implications.
PMID- 28691761
TI - A randomized pilot trial of a videoconference couples communication intervention
for advanced GI cancer.
AB - OBJECTIVE: This study aims to test the feasibility and preliminary efficacy of a
couple-based communication intervention for advanced GI cancer delivered via
videoconference. METHODS: Thirty-two couples were randomly assigned to either
couples communication skills training (CCST) or an education comparison
intervention, both delivered via videoconference. Participation was limited to
couples who reported communication difficulties at screening. Patients and
partners completed measures of relationship functioning and individual
functioning at baseline and post-intervention. RESULTS: Eighty-eight percent of
randomized dyads completed all six sessions and reported high levels of
satisfaction with the intervention. Between-group effect sizes suggested that the
CCST intervention led to improvements in relationship satisfaction for patients
and partners and to improvements in intimacy and communication for patients.
CONCLUSIONS: A couples-based communication intervention delivered via
videoconference is feasible and acceptable in the context of advanced cancer.
Preliminary findings suggest that the intervention shows promise in contributing
to enhanced relationship functioning. Copyright (c) 2016 John Wiley & Sons, Ltd.
PMID- 28691762
TI - Comparison of fully wettable RPLC stationary phases for LC-MS-based cellular
metabolomics.
AB - Reversed-phase LC combined with high-resolution mass spectrometry (HRMS) is one
of the most popular methods for cellular metabolomics studies. Due to the
difficulties in analyzing a wide range of polarities encountered in the
metabolome, 100%-wettable reversed-phase materials are frequently used to
maximize metabolome coverage within a single analysis. Packed with silica-based
sub-3 MUm diameter particles, these columns allow high separation efficiency and
offer a reasonable compromise for metabolome coverage within a single analysis.
While direct performance comparison can be made using classical chromatographic
characterization approaches, a comprehensive assessment of the column's
performance for cellular metabolomics requires use of a full LC-HRMS workflow in
order to reflect realistic study conditions used for cellular metabolomics. In
this study, a comparison of several reversed-phase LC columns for metabolome
analysis using such a dedicated workflow is presented. All columns were tested
under the same analytical conditions on an LC-TOF-MS platform using a variety of
authentic metabolite standards and biotechnologically relevant yeast cell
extracts. Data on total workflow performance including retention behavior, peak
capacity, coverage, and molecular feature extraction repeatability from these
columns are presented with consideration for both nontargeted screening and
differential metabolomics workflows using authentic standards and Pichia pastoris
cell extract samples.
PMID- 28691763
TI - On being a fat medical student, at the start of our metabolism module.
PMID- 28691764
TI - Cten promotes epithelial-mesenchymal transition through the post-transcriptional
stabilization of Snail.
AB - Cten promotes cell migration however the knowledge of underlying signalling
pathways is sparse. We have shown that Cten downregulates E-cadherin, a feature
of epithelial to mesenchymal transition (EMT). This prompted us to investigate
whether Cten further contributed to EMT processes to regulate cell motility. The
regulation of Snail by Cten was investigated following overexpression, knockdown
(by RNA-interference) or knockout of Cten in HCT116, Caco-2 and SW620 colorectal
cancer (CRC) cell lines. Subsequently, the cycloheximide (CHX) pulse chase assay
was used to investigate changes in Snail protein stability and the functional
relevance of Cten-Snail signalling was investigated. Snail was identified as a
downstream target of Cten signalling using multiple approaches of Cten expression
manipulation. Furthermore, this activity was mediated through the SH2 domain of
Cten. The CHX assay confirmed that Cten was regulating Snail at a post
transcriptional level and this was through the prevention of Snail degradation.
Cell migration, invasion and colony formation efficiency were increased following
forced expression of GFP-Cten but subsequently lost when Snail was knocked down,
demonstrating a functional Cten-Snail signalling axis. In conclusion, we have
described a novel Cten-Snail signaling pathway that contributes to cell motility
in CRC, mediated by the stabilization of Snail protein. This finding potentially
furthers the understanding of EMT regulatory networks in cancer metastasis.
PMID- 28691765
TI - Cooking with Active Oxygen and Solid Alkali: A Promising Alternative Approach for
Lignocellulosic Biorefineries.
AB - Lignocellulosic biomass, a matrix of biopolymers including cellulose,
hemicellulose, and lignin, has gathered increasing attention in recent years for
the production of chemicals, fuels, and materials through biorefinery processes
owing to its renewability and availability. The fractionation of lignocellulose
is considered to be the fundamental step to establish an economical and
sustainable lignocellulosic biorefinery. In this Minireview, we summarize a newly
developed oxygen delignification for lignocellulose fractionation called cooking
with active oxygen and solid alkali (CAOSA), which can fractionate lignocellulose
into its constituents and maintain its processable form. In the CAOSA approach,
environmentally friendly chemicals are applied instead of undesirable chemicals
such as strong alkalis and sulfides. Notably, the alkali recovery for this
process promises to be relatively simple and does not require causticizing or
sintering. These features make the CAOSA process an alternative for both
lignocellulose fractionation and biomass pretreatment. The advantages and
challenges of CAOSA are also discussed to provide a comprehensive perspective
with respect to existing strategies.
PMID- 28691766
TI - Detection of metabolites of the new synthetic cannabinoid CUMYL-4CN-BINACA in
authentic urine samples and human liver microsomes using high-resolution mass
spectrometry.
AB - CUMYL-4CN-BINACA(1-(4-cyanobutyl)-N-(2-phenylpropan-2-yl)-1H-indazole-3
carboxamide) is a recently introduced indazole-3-carboxamide-type synthetic
cannabinoid (SC) that was detected in herbal incense seized by of the Council of
Forensic Medicine, Istanbul Narcotics Department, in May 2016 in Turkey. Recently
introduced SCs are not detected in routine toxicological analysis; therefore,
analytical methods to measure these compounds are in demand. The present study
aims to identify urinary marker metabolites of CUMYL-4CN-BINACA by investigating
its metabolism in human liver microsomes and to confirm the results in authentic
urine samples (n = 80). In this study, 5 MUM CUMYL-4CN-BINACA was incubated with
human liver microsomes (HLMs) for up to 3 hours, and metabolites were identified
using liquid chromatography-high-resolution mass spectrometry (LC-HRMS). Less
than 21% of the CUMYL-4CN-BINACA parent compound remained after 3 hours of
incubation. We identified 18 metabolites that were formed via monohydroxylation,
dealkylation, oxidative decyanation to aldehyde, alcohol, and carboxylic acid
formation, glucuronidation or reaction combinations. CUMYL-4CN-BINACA N-butanoic
acid (M16) was found to be major metabolite in HLMs. In urine samples CUMYL-4CN
BINACA was not detected; CUMYL-4CN-BINACA N-butanoic acid (M16) was major
metabolite after beta-glucuronidase hydrolysis. Based on these findings, we
recommend using M16 (CUMYL-4CN-BINACA N-butanoic acid), M8 and M11 (hydroxylcumyl
CUMYL-4CN-BINACA) as urinary marker metabolites to confirm CUMYL-4CN-BINACA
intake.
PMID- 28691767
TI - Improvement of solid-phase microextraction efficiency by the application of a
carbon-nanotubes-based ternary microextraction fiber composite.
AB - In this study, a novel technique is proposed for preparation of an efficient and
unbreakable metal-wire-supported solid-phase microextraction fiber. A sol-gel
film was deposited on electrophoretically deposited carbon nanotubes on a
stainless-steel wire. The applicability of the fiber was evaluated through the
extraction of some aromatic pollutants as model compounds from the headspace of
aqueous samples in combination with gas chromatography and mass spectrometry. The
parameters affecting the structure and extraction efficiency of the fiber
(including the type of solvent, time, and potential for electrophoretic
deposition) and the parameters affecting the extraction efficiency (such as
coating type, salt content, extraction temperature, and time) were investigated.
The results showed that the film thickness will be increased by increasing the
potential and time duration. Finally, the characterization of the deposited film
was accomplished by scanning electron microscopy and thermogravimetric analysis.
After the optimization of the extraction parameters, the limit of detection of
less than 20 pg/mL was achieved, and the calibration curves were all linear (r2
>= 0.9737), in the range from 50 to 500 pg/mL. The solid-phase microextraction
fiber has a high mechanical strength; good stability and long service life,
making it potentially applicable in the extraction of trace polycyclic aromatic
hydrocarbons from aqueous samples.
PMID- 28691768
TI - Microbiome, inflammation, epigenetic alterations, and mental diseases.
AB - Major mental diseases such as autism, bipolar disorder, schizophrenia, and major
depressive disorder are debilitating illnesses with complex etiologies. Recent
findings show that the onset and development of these illnesses cannot be well
described by the one-gene; one-disease approach. Instead, their clinical
presentation is thought to result from the regulative interplay of a large number
of genes. Even though the involvement of many genes are likely, up regulating and
activation or down regulation and silencing of these genes by the environmental
factors play a crucial role in contributing to their pathogenesis. Much of this
interplay may be moderated by epigenetic changes. Similar to genetic mutations,
epigenetic modifications such as DNA methylation, histone modifications, and RNA
interference can influence gene expression and therefore may cause behavioral and
neuronal changes observed in mental disorders. Environmental factors such as
diet, gut microbiota, and infections have significant role in these epigenetic
modifications. Studies show that bioactive nutrients and gut microbiota can alter
either DNA methylation and histone signatures through a variety of mechanisms.
Indeed, microbes within the human gut may play a significant role in the
regulation of various elements of "gut-brain axis," via their influence on
inflammatory cytokines and production of antimicrobial peptides that affect the
epigenome through their involvement in generating short chain fatty acids,
vitamin synthesis, and nutrient absorption. In addition, they may participate in
gut production of many common neurotransmitters. In this review we will consider
the potential interactions of diet, gastrointestinal microbiome, inflammation,
and epigenetic alterations in psychiatric disorders.
PMID- 28691769
TI - Automatic recognition of the XLHED phenotype from facial images.
AB - X-linked hypohidrotic ectodermal dysplasia (XLHED) is a genetic disorder that
affects ectodermal structures and presents with a characteristic facial
appearance. The ability of automated facial recognition technology to detect the
phenotype from images was assessed . In Phase 1 of this study we examined if the
age of male patients affected the technology's recognition. In Phase 2 we
investigated how well the technology discriminated affected males cases from
female carriers and from individuals with other ectodermal dysplasia syndromes.
The system detected XLHED to be the most likely diagnosis in all genetically
confirmed affected male patients of all ages, and in 55% of heterozygous females.
Interestingly, patients with other ED syndromes were also detected by the XLHED
targeted analysis, consistent with shared developmental features. Thus the
automated facial recognition system represents a promising non-invasive
technology to screen patients at all ages for a possible diagnosis of ectodermal
dysplasia, with greatest sensitivity and specificity for males affected with
XLHED.
PMID- 28691770
TI - Influence of the Water Phase State on the Thermodynamics of Aqueous-Phase
Reforming for Hydrogen Production.
AB - Hydrogen is a promising renewable energy source that can be produced from biomass
using aqueous-phase reforming (APR). Here, using data obtained from AspenPlus and
the literature, we evaluated the phase state, temperature-dependent enthalpy, and
Gibbs free energy for the APR of small biomass model substrates. Phase
equilibrium studies reveal that, under typical APR reaction conditions, the
reaction mixture is in the liquid phase. Therefore, we show for the first time
that the water-gas shift reaction (WGSR), which is the second main reaction of
APR, must be modeled in the liquid phase, resulting in an endothermic instead of
an exothermic enthalpy of reaction. A significant implication of this finding is
that, although APR has been introduced as more energy saving than conventional
reforming methods, the WGSR in APR has a comparable energy demand to the WGSR in
steam reforming (SR).
PMID- 28691771
TI - A better model of care after surgery for early endometrial cancer - Comprehensive
needs assessment and clinical handover to a woman's general practitioner.
AB - BACKGROUND: Endometrial cancer is the most common invasive gynaecological cancer
in Australia. Despite the fact that review after treatment of early endometrial
cancer has not been shown to detect recurrent disease, practice at several
hospitals brings women back for specialist hospital review for 5 years after
definitive cancer surgery. AIM: Implement an improved model of follow-up care
following hospital treatment for early endometrial cancer. EVALUATION METHODS:
Quantitative and qualitative. RESULTS: Seventy-three of the eligible 81 women
undertook the model of care. All general practitioners (GPs) agreed to follow-up
care. Thirty-one women (42%) and 37 GPs (51%) returned surveys. All women found
the nurse consultation very useful or useful with 77% reporting making lifestyle
changes and 87% found the GP consultation very useful or useful with 72%
reporting making lifestyle changes. Eighty-nine percent of GPs found the care
plan useful, 94% set up patient recall systems, 79% used the care plan to develop
their own care plan, 100% felt confident in providing follow-up care with 91%
reporting the care plan and hospital processes improved their confidence.
Comparison with the pre-cohort women showed: higher rates of communication at
various care points to GPs (from P < 0.001); more referrals (P < 0.001); and a
projected decrease of nine hospital doctor appointments per patient. DISCUSSION:
With an increasing number of people surviving cancer, in order to address
holistic health needs and maintain tertiary service capacity, general practice
will be required to provide more follow-up care. Our model demonstrates an
acceptable and quality mechanism for this to occur.
PMID- 28691772
TI - Successful liver transplantation despite donor-transmitted ESBL-producing
Klebsiella pneumoniae infection: Case report and review of the literature.
AB - Donor-derived bacterial infection is a recognized complication of solid organ
transplantation. Patients admitted to the intensive care unit are increasingly
exposed to infection with multidrug-resistant microorganisms. However, no
specific recommendations are available about their suitability as donors. We
report a case of donor-transmitted extended-spectrum beta-lactamase-producing
Klebsiella pneumoniae infection in a liver recipient, and review the related
literature.
PMID- 28691773
TI - Visualization of Aged Fingerprints with an Ultraviolet Laser.
AB - Detection of aged fingerprints is difficult because they can degrade over time
with exposure to light, moisture, and temperature. In this study, aging
fingerprints were visualized by time-resolved spectroscopy with an ultraviolet
pulsed laser. Fingerprints were prepared on glass slides and paper and then
stored under three lighting conditions and two humidity conditions for up to a
year. The fluorescence intensities of the fingerprints decreased with time.
Samples were stored in the dark degraded less than in sunlight or under a
fluorescent lamp. Samples were stored under low humidity degraded less than under
moderate humidity. As the storage period increased, a fluorescence emission peak
appeared that was at a longer wavelength than the peak visible in earlier
spectra. This peak was used for visualization of an aged fingerprint over time.
An image of the fingerprint was not initially visible, but an image appeared as
the time since deposition of the fingerprint increased.
PMID- 28691774
TI - Bite Mark Analysis in Foodstuffs and Inanimate Objects and the Underlying Proofs
for Validity and Judicial Acceptance.
AB - Even though one of the first bite mark cases was Doyle v. State in 1954 (a bitten
cheese case), the research has focused on bite marks inflicted in human skin. As
published Papers, Case Reports, or Technical Notes can constitute precedents
which are relied upon in making the legal arguments and a considerable amount of
case law exists in this area, we present a systematic review on bite mark
analysis in foodstuffs and inanimate objects and their underlying proofs for
validity and judicial acceptance according to Daubert rulings. Results showed
that there is vulnerability in these procedures, and it is essential to demand
for focus scrutiny on the known error rates when such evidence is presented in
trials. These kinds of bite marks are well documented; however, there has been
little research in this field knowing that the protocols of analysis and
comparison are the responsibility of the forensic odontologists.
PMID- 28691775
TI - Short Peptides Directing 1D Helical Arrays of Polyoxometalates with Controllable
Pitches.
AB - A series of cationic peptides with alternating hydrophilic and hydrophobic
residues were elaborately designed and synthesized. These kinds of short peptides
with protonated lysine groups can interact with anionic polyoxometalate
nanoclusters through multivalent ionic bonds and hydrogen bonds, resulting in the
formation of helical polyoxometalate arrays in aqueous solution. Fourier
transform infrared (FTIR) spectroscopy, circular dichroism (CD), transmission
electron microscopy (TEM), and dynamic light scattering (DLS) were utilized to
characterize the self-assembled structures. TEM revealed that the polyoxometalate
clusters form periodic arrays within the helical nanofibers. This work reports
that the handedness of the helical fibers was attributed to the precise chirality
expression of peptides. The l-type peptide directed the formation of left-handed
polyoxometalate arrays, whereas right-handed polyoxometalate arrays were observed
when the peptide was constituted by d-amino acids. It was also found that the
pitch of the helical nanofibers is inversely proportional to the hydrophobicity
of peptides with less hydrophobicity giving a larger helical pitch.
PMID- 28691776
TI - A Simple Method of VNTR D1S80 Locus Allelic Ladder Construction for Capillary
Electrophoresis-based Genotyping.
AB - VNTR D1S80 locus genotyping has been largely replaced in forensics by STR. As the
statute of limitations on murder cases was abolished in the Republic of Korea in
July 2015, the demand for re-analysis of DNA from unresolved murder cases has
increased. The National Forensic Service includes several recorded D1S80
genotypes as crucial clues. Here, we re-established the D1S80 analysis system
using capillary electrophoresis and confirmed the reproducibility of the system
by comparison with the genotypes of eight DNA samples that had been analyzed
using PAGE in 2006. In addition, we created an allelic ladder via new methodology
using flanking region sequences. A single DNA sample (K562) and seven primers
were used for the new ladder, which contains 12 alleles. Although artificial
owing to the use of the flanking region rather than repeat unit reduction, the
method is rapid and simple, and could be applicable in any laboratory.
PMID- 28691778
TI - A different way to study frequency volume charts in patients with nocturia.
AB - BACKGROUND: Nocturia results from a mismatch between bladder capacity and
nocturnal urine production (NUP), which is determined with a frequency volume
charts (FVC). AIM: This is the first study that aimed to describe variations in
nocturia severity and its associated factors by evaluating FVCs per single 24 h
period. METHODS: This was a post-hoc analysis of patients who completed a 72 h
FVC in prospective, observational studies. The nocturnal polyuria index (NPi )
was defined as the ratio of nocturnal and 24 h urine output. Subgroups were
defined according to variations in nocturia frequency during the three 24 h
periods of the FVC (fluctuating/consistent) and to the number of nocturia
episodes during a single night (0/1/>=2). RESULTS: We analyzed 504 24 h-FVC,
collected by 168 subjects (58% female) with a median age of 60 (50-68) years.
Nocturia frequency fluctuated in 69 (41%) subjects. For the same number of
nocturnal voids, we found no differences in NPi and maximum voided volume (MVV)
between consistent and fluctuating nocturia frequency. Increasing numbers of
nocturnal voids were associated with an increasing NPi in subjects with
fluctuating nocturia, while for consistent nocturia, it was linked to an increase
in NPi and a decrease in MVV. For both subjects with fluctuating and consistent
nocturia, increasing nocturia severity was associated with increasing daytime
fluid intake. CONCLUSION: For the same number of nocturnal voids, bladder
capacity, and NUP were similar between patients with consistent and fluctuating
nocturia. An increasing number of nocturnal voids in subjects with fluctuating
nocturia was linked to more NUP and more daytime fluid intake.
PMID- 28691777
TI - Structure and evolution of ENTH and VHS/ENTH-like domains in tepsin.
AB - Tepsin is currently the only accessory trafficking protein identified in adaptor
related protein 4 (AP4)-coated vesicles originating at the trans-Golgi network
(TGN). The molecular basis for interactions between AP4 subunits and motifs in
the tepsin C-terminus have been characterized, but the biological role of tepsin
remains unknown. We determined X-ray crystal structures of the tepsin epsin N
terminal homology (ENTH) and VHS/ENTH-like domains. Our data reveal unexpected
structural features that suggest key functional differences between these and
similar domains in other trafficking proteins. The tepsin ENTH domain lacks
helix0, helix8 and a lipid binding pocket found in epsin1/2/3. These results
explain why tepsin requires AP4 for its membrane recruitment and further suggest
ENTH domains cannot be defined solely as lipid binding modules. The VHS domain
lacks helix8 and thus contains fewer helices than other VHS domains. Structural
data explain biochemical and biophysical evidence that tepsin VHS does not
mediate known VHS functions, including recognition of dileucine-based cargo
motifs or ubiquitin. Structural comparisons indicate the domains are very similar
to each other, and phylogenetic analysis reveals their evolutionary pattern
within the domain superfamily. Phylogenetics and comparative genomics further
show tepsin within a monophyletic clade that diverged away from epsins early in
evolutionary history (~1500 million years ago). Together, these data provide the
first detailed molecular view of tepsin and suggest tepsin structure and function
diverged away from other epsins. More broadly, these data highlight the
challenges inherent in classifying and understanding protein function based only
on sequence and structure.
PMID- 28691779
TI - Mercury speciation and subcellular distribution in experimentally dosed and wild
birds.
AB - Many bird species are exposed to methylmercury (MeHg) at levels shown to cause
sublethal effects. Although MeHg sensitivity and assimilation can vary among
species and developmental stages, the underlying reasons (such as MeHg
toxicokinetics) are poorly understood. We investigated Hg distribution at the
tissue and cellular levels in birds by examining Hg speciation in blood, brain,
and liver and Hg subcellular distribution in liver. We used MeHg egg injection of
white leghorn chicken (Gallus gallus domesticus), sampled at 3 early
developmental stages, and embryonic ring-billed gulls (Larus delawarensis)
exposed to maternally deposited MeHg. The percentage of MeHg (relative to total
Hg [THg]) in blood, brain, and liver ranged from 94 to 121%, indicating little
MeHg demethylation. A liver subcellular partitioning procedure was used to
determine how THg was distributed between potentially sensitive and detoxified
compartments. The distributions of THg among subcellular fractions were similar
among chicken time points, and between embryonic chicken and ring-billed gulls. A
greater proportion of THg was associated with metal-sensitive fractions than
detoxified fractions. Within the sensitive compartment, THg was found
predominately in heat-denatured proteins (~42-46%), followed by mitochondria (~15
18%). A low rate of MeHg demethylation and high proportion of THg in metal
sensitive subcellular fractions further indicates that embryonic and hatchling
time points are Hg-sensitive developmental stages, although further work is
needed across a range of additional species and life stages. Environ Toxicol Chem
2017;36:3289-3298. (c) 2017 SETAC.
PMID- 28691780
TI - Development of cultures of the marine sponge Hymeniacidon perleve for
genotoxicity assessment using the alkaline comet assay.
AB - Sponges are a potential alternative model species to bivalves in pollution
biomonitoring and environmental risk assessment in the aquatic ecosystem. In the
present study, a novel in vivo exposure sponge culture model was developed from
field-collected and cryopreserved sponge (Hymeniacidon perleve) cells to
investigate the genotoxic effects of environmentally relevant metals in the
laboratory. Sponge cell aggregates were cultured and exposed to noncytotoxic
concentrations (0-0.4 mg/L) of cadmium chloride, nickel chloride, and sodium
dichromate as quantified by the reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5
diphenyltetrazolium bromide and DNA-strand breaks assessed by the comet assay.
Reactive oxygen species (ROS) formation was quantified by oxidation of 2',7'
dichlorofluorescin diacetate in sponge cell aggregates exposed to the same
concentrations of Cd, Cr, and Ni. There was a statistically significant (p <
0.05) concentration-dependent increase in the level of DNA-strand breaks and ROS
formation in all of the metals investigated. To the best of our knowledge, we
have utilized for the first time the alkaline comet assay to detect DNA-strand
breaks in marine sponge cells and demonstrated that exposure to noncytotoxic
concentrations of Cd, Cr, and Ni for 12 h results in a concentration-dependent
increase in DNA damage and levels of ROS production. In conclusion, we have
developed a novel in vivo model based on culture of cryopreserved sponge cells
that is compatible with the alkaline comet assay. Genotoxicity in marine sponges
measured by the comet assay technique may be a useful tool for biomonitoring
research and risk assessment in aquatic ecosystems. Environ Toxicol Chem
2017;36:3314-3323. (c) 2017 SETAC.
PMID- 28691781
TI - Acute malaria in a repeat blood donor.
PMID- 28691782
TI - A novel microduplication of ARID1B: Clinical, genetic, and proteomic findings.
AB - Genetic alterations of ARID1B have been recently recognized as one of the most
common mendelian causes of intellectual disability and are associated with both
syndromic and non-syndromic phenotypes. The ARID1B protein, a subunit of the
chromatin remodeling complex SWI/SNF-A, is involved in the regulation of
transcription and multiple downstream cellular processes. We report here the
clinical, genetic, and proteomic phenotypes of an individual with a unique
apparent de novo mutation of ARID1B due to an intragenic duplication. His
neurodevelopmental phenotype includes a severe speech/language disorder with full
scale IQ scores 78-98 and scattered academic skill levels, expanding the
phenotypic spectrum of ARID1B mutations. Haploinsufficiency of ARID1B was
determined both by RNA sequencing and quantitative RT-PCR. Fluorescence in situ
hybridization analysis supported an intragenic localization of the ARID1B copy
number gain. Principal component analysis revealed marked differentiation of the
subject's lymphoblast proteome from that of controls. Of 3426 proteins
quantified, 1014 were significantly up- or down-regulated compared to controls (q
< 0.01). Pathway analysis revealed highly significant enrichment for canonical
pathways of EIF2 and EIF4 signaling, protein ubiquitination, tRNA charging and
chromosomal replication, among others. Network analyses revealed down-regulation
of: (1) intracellular components involved in organization of membranes,
organelles, and vesicles; (2) aspects of cell cycle control, signal transduction,
and nuclear protein export; (3) ubiquitination and proteosomal function; and (4)
aspects of mRNA synthesis/splicing. Further studies are needed to determine the
detailed molecular and cellular mechanisms by which constitutional
haploinsufficiency of ARID1B causes syndromic and non-syndromic developmental
disabilities.
PMID- 28691783
TI - Two-Step Synthesis of Complex Artificial Macrocyclic Compounds.
AB - The design and synthesis of head-to-tail linked artificial macrocycles using the
Ugi-reaction has been developed. This synthetic approach of just two steps is
unprecedented, short, efficient and works over a wide range of medium (8-11) and
macrocyclic (>=12) loop sizes. The substrate scope and functional group tolerance
is exceptional. Using this approach, we have synthesized 39 novel macrocycles by
two or even one single synthetic operation. The properties of our macrocycles are
discussed with respect to their potential to bind to biological targets that are
not druggable by conventional, drug-like compounds. As an application of these
artificial macrocycles we highlight potent p53-MDM2 antagonism.
PMID- 28691785
TI - Two-Year Outcome after Endovascular Treatment for Stroke.
PMID- 28691786
TI - Regulatory Review of New Therapeutic Agents.
PMID- 28691784
TI - Epigenome-wide association of PTSD from heterogeneous cohorts with a common multi
site analysis pipeline.
AB - Compelling evidence suggests that epigenetic mechanisms such as DNA methylation
play a role in stress regulation and in the etiologic basis of stress related
disorders such as Post traumatic Stress Disorder (PTSD). Here we describe the
purpose and methods of an international consortium that was developed to study
the role of epigenetics in PTSD. Inspired by the approach used in the Psychiatric
Genomics Consortium, we brought together investigators representing seven cohorts
with a collective sample size of N = 1147 that included detailed information on
trauma exposure, PTSD symptoms, and genome-wide DNA methylation data. The
objective of this consortium is to increase the analytical sample size by pooling
data and combining expertise so that DNA methylation patterns associated with
PTSD can be identified. Several quality control and analytical pipelines were
evaluated for their control of genomic inflation and technical artifacts with a
joint analysis procedure established to derive comparable data over the cohorts
for meta-analysis. We propose methods to deal with ancestry population
stratification and type I error inflation and discuss the advantages and
disadvantages of applying robust error estimates. To evaluate our pipeline, we
report results from an epigenome-wide association study (EWAS) of age, which is a
well-characterized phenotype with known epigenetic associations. Overall, while
EWAS are highly complex and subject to similar challenges as genome-wide
association studies (GWAS), we demonstrate that an epigenetic meta-analysis with
a relatively modest sample size can be well-powered to identify epigenetic
associations. Our pipeline can be used as a framework for consortium efforts for
EWAS.
PMID- 28691787
TI - Drug Combinations with Transplantation for Myeloma
PMID- 28691788
TI - Body-Weight Fluctuations and Outcomes in Coronary Disease.
PMID- 28691789
TI - Body-Weight Fluctuations and Outcomes in Coronary Disease.
PMID- 28691790
TI - Conscientious Objection in Health Care.
PMID- 28691791
TI - Conscientious Objection in Health Care.
PMID- 28691792
TI - High-Performance Li-Se Batteries Enabled by Selenium Storage in Bottom-Up
Synthesized Nitrogen-Doped Carbon Scaffolds.
AB - Selenium (Se) has great promise to serve as cathode material for rechargeable
batteries because of its good conductivity and high theoretical volumetric energy
density comparable to sulfur. Herein, we report the preparation of mesoporous
nitrogen-doped carbon scaffolds (NCSs) to restrain selenium for advanced lithium
selenium (Li-Se) batteries. The NCSs synthesized by a bottom-up solution-phase
method have graphene-like laminar structure and well-distributed mesopores. The
unique architecture of NCSs can severe as conductive framework for encapsulating
selenium and polyselenides, and provide sufficient pathways to facilitate ion
transport. Furthermore, the laminar and porous NCSs can effectively buffer the
volume variation during charge/discharge processes. The integrated composite of
Se-NCSs has a high Se content and can ensure the complete electrochemical
reactions of Se and Li species. When used for Li-Se batteries, the cathodes based
on Se-NCSs exhibit high capacity, remarkable cyclability, and excellent rate
performance.
PMID- 28691793
TI - Graphene-Roll-Wrapped Prussian Blue Nanospheres as a High-Performance Binder-Free
Cathode for Sodium-Ion Batteries.
AB - Sodium iron hexacyanoferrate (Fe-HCF) has been proposed as a promising cathode
material for sodium-ion batteries (SIBs) because of its desirable advantages,
including high theoretical capacity (~170 mAh g-1), eco-friendliness, and low
cost of worldwide rich sodium and iron resources. Nonetheless, its application
faces a number of obstacles due to poor electronic conductivity and structural
instability. In this work, Fe-HCF nanospheres (NSs) were first synthesized and
fabricated by an in situ graphene rolls (GRs) wrapping method, forming a 1D
tubular hierarchical structure of Fe-HCF NSs@GRs. GRs not only provide fast
electronic conduction path for Fe-HCF NSs but also effectively prevent organic
electrolyte from reaching active materials and inhibit the occurrence of side
reactions. The Fe-HCF NSs@GRs composite has been used as a binder-free cathode
with a capacity of ~110 mAh g-1 at a current density of 150 mA g-1 (~1C), the
capacity retention of ~90% after 500 cycles. Moreover, the Fe-HCF NSs@GRs cathode
displays a super high rate capability with ~95 mAh g-1 at 1500 mA g-1 (~10C). The
results suggest that the 1D tubular structure of 2D GRs-wrapped Fe-HCF NSs is
promising as a high-performance cathode for SIBs.
PMID- 28691795
TI - Copper-Based Metal-Organic Framework Nanoparticles with Peroxidase-Like Activity
for Sensitive Colorimetric Detection of Staphylococcus aureus.
AB - Cu-MOF nanoparticles with an average diameter of 550 nm were synthesized from 2
aminoterephthalic acid and Cu(NO3)2 by a mixed solvothermal method. The Cu-MOF
nanoparticles can show peroxidase-like activity that can catalyze 3,3',5,5'
tetramethylbenzidine to produce a yellow chromogenic reaction in the presence of
H2O2. The presence of abundant amine groups on the surfaces of Cu-MOF
nanoparticles enables facile modification of Staphylococcus aureus (S. aureus)
aptamer on Cu-MOF nanoparticles. By combining Cu-MOF-catalyzed chromogenic
reaction with aptamer recognition and magnetic separation, a simple, sensitive,
and selective colorimetric method for the detection of S. aureus was developed.
PMID- 28691794
TI - Ligand Dependent Switch from RXR Homo- to RXR-NURR1 Heterodimerization.
AB - Retinoid X receptors (RXRs) play key roles in many physiological processes in
both the periphery and central nervous system. In addition, RXRs form
heterodimers with other nuclear receptors to exert their physiological effects.
The nuclear receptor related 1 protein (NURR1) is particularly interesting
because of its role in promoting differentiation and survival of dopamine
neurons. However, only a small number of RXR-heterodimer selective modulators are
available, with limited chemical diversity. This work describes the synthesis,
biochemical evaluation, and structural elucidation of a novel series of RXR
ligands with strongly biased interactions with RXRalpha-NURR1 heterodimers.
Targeted modifications to the small molecule biaryl scaffold caused local
RXRalpha side-chain disturbances and displacement of secondary structural
elements upon ligand binding. This resulted in the repositioning of protein
helices in the heterodimer interface of RXRalpha, alterations in homo- versus
heterodimer formation, and modulation of activation function 2 (AF2). The data
provide a rationale for the design of RXR ligands consisting of a highly
conserved hydrophilic region, strongly contributing to the ligand affinity, and a
variable hydrophobic region, which efficiently probes the effects of structural
changes at the level of the ligand on co-regulator recruitment or the RXRalpha
NURR1 dimerization interface.
PMID- 28691796
TI - Oxidation of a Dimethoxyhydroquinone by Ferrihydrite and Goethite Nanoparticles:
Iron Reduction versus Surface Catalysis.
AB - Hydroquinones are important mediators of electron transfer reactions in soils
with a capability to reduce Fe(III) minerals and molecular oxygen, and thereby
generating Fenton chemistry reagents. This study focused on 2,6-dimethoxy
hydroquinone (2,6-DMHQ), an analogue to a common fungal metabolite, and its
reaction with ferrihydrite and goethite under variable pH and oxygen
concentrations. Combined wet-chemical and spectroscopic analyses showed that both
minerals effectively oxidized 2,6-DMHQ in the presence of oxygen. Under anaerobic
conditions the first-order oxidation rate constants decreased by one to several
orders of magnitude depending on pH and mineral. Comparison between aerobic and
anaerobic results showed that ferrihydrite promoted 2,6-DMHQ oxidation both via
reductive dissolution and heterogeneous catalysis while goethite mainly caused
catalytic oxidation. These results were in agreement with changes in the
reduction potential (EH) of the Fe(III) oxide/Fe(II)aq redox couple as a function
of dissolved Fe(II) where EH of goethite was lower than ferrihydrite at any given
Fe(II) concentration, which makes ferrihydrite more prone to reductive
dissolution by the 2,6-DMBQ/2,6-DMHQ redox couple. This study showed that
reactions between hydroquinones and iron oxides could produce favorable
conditions for formation of reactive oxygen species, which are required for
nonenzymatic Fenton-based decomposition of soil organic matter.
PMID- 28691797
TI - Caught before Released: Structural Mapping of the Reaction Trajectory for the
Sofosbuvir Activating Enzyme, Human Histidine Triad Nucleotide Binding Protein 1
(hHint1).
AB - Human histidine triad nucleotide binding protein 1 (hHint1) is classified as an
efficient nucleoside phosphoramidase and acyl-adenosine monophosphate hydrolase.
Human Hint1 has been shown to be essential for the metabolic activation of
nucleotide antiviral pronucleotides (i.e., proTides), such as the FDA approved
hepatitis C drug, sofosbuvir. The active site of hHint1 comprises an ensemble of
strictly conserved histidines, including nucleophilic His112. To structurally
investigate the mechanism of hHint1 catalysis, we have designed and prepared
nucleoside thiophosphoramidate substrates that are able to capture the
transiently formed nucleotidylated-His112 intermediate (E*) using time-dependent
crystallography. Utilizing a catalytically inactive hHint1 His112Asn enzyme
variant and wild-type enzyme, the enzyme-substrate (ES1) and product (EP2)
complexes were also cocrystallized, respectively, thus providing a structural map
of the reaction trajectory. On the basis of these observations and the
mechanistic necessity of proton transfers, proton inventory studies were carried
out. Although we cannot completely exclude the possibility of more than one
proton in flight, the results of these studies were consistent with the transfer
of a single proton during the formation of the intermediate. Interestingly,
structural analysis revealed that the critical proton transfers required for
intermediate formation and hydrolysis may be mediated by a conserved active site
water channel. Taken together, our results provide mechanistic insights
underpinning histidine nucleophilic catalysis in general and hHint1 catalysis, in
particular, thus aiding the design of future proTides and the elucidation of the
natural function of the Hint family of enzymes.
PMID- 28691798
TI - Structure and Affinity of Two Bicyclic Glutamate Analogues at AMPA and Kainate
Receptors.
AB - Ionotropic glutamate receptors (iGluRs) are involved in most of the fast
excitatory synaptic transmission in the central nervous system. These receptors
are important for learning and memory formation, but are also involved in the
development of diseases such as Alzheimer's disease, epilepsy and depression. To
understand the function of different types of iGluRs, selective agonists are
invaluable as pharmacological tool compounds. Here, we report binding affinities
of two bicyclic, conformationally restricted analogues of glutamate (CIP-AS and
LM-12b) at AMPA (GluA2 and GluA3) and kainate receptor subunits (GluK1-3 and
GluK5). Both CIP-AS and LM-12b were found to be GluK3-preferring agonists, with
Ki of 6 and 22 nM, respectively, at recombinant GluK3 receptors. The detailed
binding mode of CIP-AS and LM-12b in the ligand-binding domains of the AMPA
receptor subunit GluA2 (GluA2-LBD) and the kainate receptor subunits GluK1 (GluK1
LBD) and GluK3 (GluK3-LBD) was investigated by X-ray crystallography. CIP-AS
stabilized all three receptor constructs in conformations similar to those with
kainate. Remarkably, whereas LM-12b bound in a similar manner to CIP-AS in GluA2
LBD and GluK3-LBD, it introduced full closure of the ligand-binding domain in
GluK1-LBD and formation of a D1-D2 interlobe hydrogen bond between Glu441 and
Ser721, as also observed with glutamate. As the binding affinity of LM-12b at
GluK1 is ~8-fold better than that for CIP-AS (Ki of 85 and 656 nM, respectively),
it shows that small changes in agonist structure can lead to prominent
differences in structure and function.
PMID- 28691799
TI - Solid-Contact pH Sensor without CO2 Interference with a Superhydrophobic PEDOT
C14 as Solid Contact: The Ultimate "Water Layer" Test.
AB - The aim of this study was to find a conducting polymer-based solid contact (SC)
for ion-selective electrodes (ISEs) that could become the ultimate, generally
applicable SC, which in combination with all kinds of ion-selective membranes
(ISMs) would match the performance characteristics of conventional ISEs. We
present data collected with electrodes utilizing PEDOT-C14, a highly hydrophobic
derivative of poly(3,4-ethylenedioxythiophene), PEDOT, as SC and compare its
performance characteristics with PEDOT-based SC ISEs. PEDOT-C14 has not been used
in SC ISEs previously. The PEDOT-C14-based solid contact (SC) ion-selective
electrodes (ISEs) (H+, K+, and Na+) have outstanding performance characteristics
(theoretical response slope, short equilibration time, excellent potential
stability, etc.). Most importantly, PEDOT-C14-based SC pH sensors have no CO2
interference, an essential pH sensors property when aimed for whole-blood
analysis. The superhydrophobic properties (water contact angle: 136 +/- 5 degrees
) of the PEDOT-C14 SC prevent the detachment of the ion-selective membrane (ISM)
from its SC and the accumulation of an aqueous film between the ISM and the SC.
The accumulation of an aqueous film between the ISM and its SC has a detrimental
effect on the sensor performance. Although there is a test for the presence of an
undesirable water layer, if the conditions for this test are not selected
properly, it does not provide an unambiguous answer. On the other hand, recording
the potential drifts of SC electrodes with pH-sensitive membranes in samples with
different CO2 levels can effectively prove the presence or absence of a water
layer in a short time period.
PMID- 28691800
TI - Three Lessons for the Microplastics Voyage.
PMID- 28691801
TI - Relative Antagonism of Mutants of the CGRP Receptor Extracellular Loop 2 Domain
(ECL2) Using a Truncated Competitive Antagonist (CGRP8-37): Evidence for the Dual
Involvement of ECL2 in the Two-Domain Binding Model.
AB - The second extracellular loop (ECL2) of the G protein-coupled receptor (GPCR)
family is important for ligand interaction and drug discovery. ECL2 of the family
B cardioprotective calcitonin gene-related peptide (CGRP) receptor is required
for cell signaling. Family B GPCR ligands have two regions; the N-terminus
mediates receptor activation, and the remainder confers high-affinity binding.
Comparing antagonism of CGRP8-37 at a number of point mutations of ECL2 of the
CGRP receptor, we show that the ECL2 potentially facilitates interaction with up
to the 18 N-terminal residues of CGRP. This has implications for understanding
family B GPCR activation and for drug design at the CGRP receptor.
PMID- 28691802
TI - Porous-Nickel-Scaffolded Tin-Antimony Anodes with Enhanced Electrochemical
Properties for Li/Na-Ion Batteries.
AB - The energy and power densities of rechargeable batteries urgently need to be
increased to meet the ever-increasing demands of consumer electronics and
electric vehicles. Alloy anodes are among the most promising candidates for next
generation high-capacity battery materials. However, the high capacities of alloy
anodes usually suffer from some serious difficulties related to the volume
changes of active materials. Porous supports and nanostructured alloy materials
have been explored to address these issues. However, these approaches seemingly
increase the active material-based properties and actually decrease the electrode
based capacity because of the oversized pores and heavy mass of mechanical
supports. In this study, we developed an ultralight porous nickel to scaffold
with high-capacity SnSb alloy anodes. The porous-nickel-supported SnSb alloy
demonstrates a high specific capacity and good cyclability for both Li-ion and Na
ion batteries. Its capacity retains 580 mA h g-1 at 2 A g-1 after 100 cycles in
Li-ion batteries. For a Na-ion battery, the composite electrode can even deliver
a capacity of 275 mA h g-1 at 1 A g-1 after 1000 cycles. This study demonstrates
that combining the scaffolding function of ultralight porous nickel and the high
capacity of the SnSb alloy can significantly enhance the electrochemical
performances of Li/Na-ion batteries.
PMID- 28691803
TI - Development of an Activatable Fluorescent Probe for Prostate Cancer Imaging.
AB - Technology to visualize small prostate cancers is urgently needed because of the
difficulty of discriminating prostate cancer from normal tissue with the naked
eye, and a fluorescence imaging method would be advantageous. Here, we describe
the design and synthesis of a fluorogenic probe (Ac-KQLR-HMRG) that is activated
by hepsin and matriptase (proteases over-expressed in prostate cancer). Ac-KQLR
HMRG exhibited significant turn-on fluorogenicity in the presence of hepsin (180
fold) and matriptase (80-fold) and allowed specific fluorescence imaging of
various prostate cancer cell line in vitro. In addition, the probe enabled rapid
imaging (within 1-10 min) of small prostate cancer nodules in mouse models of
disseminated peritoneal tumor and orthotopic tumor.
PMID- 28691804
TI - Toxicity of Wastewater with Elevated Bromide and Iodide after Chlorination,
Chloramination, or Ozonation Disinfection.
AB - Water reuse is receiving unprecedented attention as many areas around the globe
attempt to better-manage their fresh water resources. Wastewaters in coastal
regions may contain elevated levels of bromide (Br-) and iodide (I-) from
seawater intrusion or high mineral content in the source waters. Disinfection of
such wastewater is essential to prevent the spread of pathogens; however, little
is known about the toxicity of the treated wastewater. In this study, we
evaluated the genotoxicity to Chinese hamster ovary (CHO) cells induced by
municipal secondary wastewater effluent amended with elevated Br- and I- after
disinfection by chlorine, chloramines, or ozone. We calibrated and applied an N
acetylcysteine (NAC) thiol reactivity assay as a surrogate for thiol reactivity
with biological proteins (glutathione) of wastewater samples. Chlorination of
wastewaters produced CHO cell genotoxicity comparable to chloramination, 3.9
times more genotoxic than the nondisinfected controls. Ozonated wastewater was at
least 3 times less genotoxic than the samples treated with chlorine-based
disinfectants and was not significantly different compared with the
nondisinfected controls. Positive and significant correlations were observed
among genotoxicity, cytotoxicity, and NAC thiol reactivity for all disinfected
samples. These results indicate that the ozonation of wastewater with high Br-
and I- levels may yield organics with lower genotoxicity to CHO cells than
chlorine-based disinfection. NAC thiol reactivity, although excluding the
possible effect of bromate from ozonation in this work, could be used as a rapid
in chemico screen for potential genotoxicity and cytotoxicity in mammalian cells
exposed to disinfected wastewaters.
PMID- 28691805
TI - How Does the P7C3-Series of Neuroprotective Small Molecules Prevent Membrane
Disruption?
AB - Molecular dynamics (MD) simulations are conducted to suggest a mechanism of
action for the aminopropyl dibromocarbazole derivative (P7C3) small molecule,
which protects neurons from apoptotic cell death. At first, the influence of
embedded Abeta42 stacks on the structure of membrane is studied. Then, the effect
of P7C3 molecules on the Abeta42 fibril enriched membrane and Abeta42 fibril
depleted membrane (when Abeta42 fibrils are originally dissolved in the aqueous
phase) are evaluated. Also, the formation of an amyloid ion channel in the
Abeta42 enriched membrane is examined by calculating deuterium order parameter,
density profile, and surface thickness. For Abeta42 in the fully inserted state,
ion channel-like structures are formed. The presence of P7C3 molecules in this
case just postpones membrane destruction but could not prevent pore formation. In
contrast, when both Abeta42 and P7C3 molecules are embedded in the aqueous
solution, the P7C3 molecules are self-assembled at membrane/ionic aqueous
solution interface and prevent the precipitation and deposition of Abeta42
fibrils into the membrane.
PMID- 28691806
TI - Automatic Assignment of Methyl-NMR Spectra of Supramolecular Machines Using Graph
Theory.
AB - Methyl groups are powerful probes for the analysis of structure, dynamics and
function of supramolecular assemblies, using both solution- and solid-state NMR.
Widespread application of the methodology has been limited due to the challenges
associated with assigning spectral resonances to specific locations within a
biomolecule. Here, we present Methyl Assignment by Graph Matching (MAGMA), for
the automatic assignment of methyl resonances. A graph matching protocol examines
all possibilities for each resonance in order to determine an exact assignment
that includes a complete description of any ambiguity. MAGMA gives 100% accuracy
in confident assignments when tested against both synthetic data, and 9 cross
validated examples using both solution- and solid-state NMR data. We show that
this remarkable accuracy enables a user to distinguish between alternative
protein structures. In a drug discovery application on HSP90, we show the method
can rapidly and efficiently distinguish between possible ligand binding modes. By
providing an exact and robust solution to methyl resonance assignment, MAGMA can
facilitate significantly accelerated studies of supramolecular machines using
methyl-based NMR spectroscopy.
PMID- 28691807
TI - Spectroscopic Determination of Aerosol pH from Acid-Base Equilibria in Inorganic,
Organic, and Mixed Systems.
AB - Atmospheric aerosol acidity impacts key multiphase processes, such as acid
catalyzed reactions leading to secondary organic aerosol formation, which impact
climate and human health. However, traditional indirect methods of estimating
aerosol pH often disagree with thermodynamic model predictions, resulting in
aerosol acidity still being poorly understood in the atmosphere. Herein, a
recently developed method coupling Raman microspectroscopy with extended Debye
Huckel activity calculations to directly determine the acidity of individual
particles (1-15 MUm projected area diameter, average 6 MUm) was applied to a
range of atmospherically relevant inorganic and organic acid-base equilibria
systems (HNO3/NO3-, HC2O4-/C2O42-, CH3COOH/CH3COO-, and HCO3-/CO32-) covering a
broad pH range (-1 to 10), as well as an inorganic-organic mixture (sulfate
oxalate). Given the ionic strength of the inorganic solutions, the H+ activity,
gamma(H+), yielded lower values (0.68-0.75) than the organic and mixed systems
(0.72-0.80). A consistent relationship between increasing peak broadness with
decreasing pH was observed for acidic species, but not their conjugate bases.
Greater insight into spectroscopic responses to acid-base equilibria for more
complicated mixtures is still needed to understand the behavior of atmospheric
aerosols.
PMID- 28691808
TI - ATR-FTIR and Flow Microcalorimetry Studies on the Initial Binding Kinetics of
Arsenicals at the Organic-Hematite Interface.
AB - The environmental fate of arsenic compounds depends on their surface interactions
with geosorbents that include clays, metal oxides, and natural organic matter
(NOM). While a number of batch studies reported that NOM inhibits the uptake of
arsenicals, it remains unclear how different classes of organic functional groups
affect their binding mechanisms. We report herein the adsorption kinetics of
arsenate and dimethylarsinic acid (DMA) with hematite nanoparticles pre-exposed
to three types of low molecular weight organics: citrate, oxalate, and
pyrocatechol as representatives to the majority of reactive organic functional
groups in NOM. These studies were conducted using attenuated total internal
reflection Fourier transform infrared spectroscopy (ATR-FTIR) and flow
microcalorimetry at pH 7 with an emphasis on the role that electrolytes (KCl,
NaCl, and KBr) play in the adsorption process. Results show that (1) negatively
charged carboxylate versus hydrophobic phenyl groups influence amounts and
initial rates of arsenicals adsorption on hematite nanoparticles to varying
degrees depending on the type of complexes they form, (2) the type of
electrolytes affects initial adsorption rate of DMA to a greater extent than
arsenate when oxalate is present on the surface, and (3) the extent of organics
retention by hematite nanoparticles is influenced by the type of the desorbing
agent.
PMID- 28691809
TI - Broad-Band-Emissive Organic-Inorganic Hybrid Semiconducting Nanowires Based on an
ABX3-Type Chain Compound.
AB - Organic-inorganic hybrid lead halide (e.g., CH3NH3PbX3, where X = CI, Br, and I)
nanowires (NWs) with remarkable electric and optical properties have recently
garnered increasing attention, owing to their structural flexibility and
tunability compared to inorganic semiconducting NWs. While most recently reported
NWs are limited to methylammonium/formamidinium three-dimensional lead halide
perovskites, it is urgent to develop new organic-inorganic hybrid semiconducting
NWs. Here, broad-band-emissive single-crystal semiconductive NWs based on a new
ABX3-type organic-inorganic chain hybrid, (2-methylpiperidine)lead tribromide,
are reported. It is believed that this work will enrich the organic-inorganic
hybrid semiconducting NWs and may provide potential applications for LED
displaying.
PMID- 28691810
TI - Measurements of the Imaginary Component of the Refractive Index of Weakly
Absorbing Single Aerosol Particles.
AB - The interaction of atmospheric aerosols with radiation remains a significant
source of uncertainty in modeling radiative forcing. Laboratory measurements of
the microphysical properties of atmospherically relevant particles is one
approach to reduce this uncertainty. We report a new method to investigate light
absorption by a single aerosol particle, inferring changes in the imaginary part
of the refractive index with a change in environmental conditions (e.g., relative
humidity) and inferring the size dependence of the optical extinction cross
section. More specifically, we present measurements of the response of single
aerosol particles to near-infrared (NIR) laser-induced heating at a wavelength of
1520 nm. Particles were composed of aqueous NaCl or (NH4)2SO4 and were studied
over ranges in relative humidity (40-85%), particle radius (1-2.2 MUm), and NIR
laser power. The ensuing size change and real component of the refractive index
were extracted from measurements of the angular variation in elastically
scattered light. From the heating-induced size change at varying NIR beam
intensities, we retrieved the change in the imaginary component of the refractive
index. In addition, cavity ring-down spectroscopy measurements monitored the
change in extinction cross section with modulation of the heating laser power.
PMID- 28691811
TI - Hydrogen Atom Abstraction Thermodynamics of a MU-1,2-Superoxo Dicopper(II)
Complex.
AB - Pyrazolate-based MU-1,2-peroxo dicopper(II) complex 1 undergoes clean 1e-
oxidation at low potential (-0.59 V vs Fc/Fc+) to yield the rather stable MU-1,2
superoxo dicopper(II) complex 3, which was characterized by spectroscopic methods
(nu(O-O) = 1070 cm-1, Delta(18O-16O) = -59 cm-1) and analyzed by DFT
calculations. 3 is also formed via H-atom abstraction from the corresponding MU
1,1-hydroperoxo dicopper(II) complex 2, while 3 itself is able to abstract H
atoms from weaker X-H bonds such as TEMPO-H to re-form 2. Kinetic and
thermodynamic analyses evidence a concerted proton-electron transfer pathway for
these processes. The thermodynamic square scheme reveals a bond dissociation free
energy of 71.7 +/- 1.1 kcal mol-1 for the hydroperoxo OO-H bond of 2.
PMID- 28691812
TI - Hydrogen Bonding versus pi-pi Stacking Interactions in Imidazolium-Oxalatoborate
Ionic Liquid.
AB - Intermolecular features like hydrogen bonding and pi-type interactions play
pivotal roles in stabilizing molecular structures in ionic liquids with planar
rings and hydrogen-bond donors and acceptors. However, the delicate interplay
among these interactions is complicated and depends on specific ion types. In
this work, ab initio molecular dynamics simulations were performed to reveal
competitive and cooperative characteristics among hydrogen bonding and pi-type
interactions in a typical imidazolium-oxalatoborate ionic liquid. Imidazolium
rings take preferential on-top parallel orientations, leading to their particular
pi-pi stacking distributions at short distances. Intermolecular interactions
between imidazolium and oxalato rings are manifested by short-range on-top
parallel orientations and in-plane hydrogen bonding interactions, promoting their
parallel displaced offset stacking arrangements. However, on an intermediate
distance scale, attractive Coulombic interactions between imidazolium and oxalato
rings dominate and contribute to their perpendicular orientations. Spatial
coordination patterns between intermolecular oxalato rings are balanced by
repulsive electrostatic interactions and steric hindrance effects, leading to
their tilted orientations in local environments.
PMID- 28691813
TI - Microbiome-Mediated Biotransformation of Cane Toad Bufagenins.
AB - Cane toads are an invasive pest species in which all life stages employ
cardiotoxic bufagenins as a chemical defense against predators. Curiously, the
bufagenin profiles of eggs and tadpoles are more complex than those of parotoid
secretion, the principle mechanism of toxin delivery in adult toads. In an effort
to understand this complexity, we determined that selected strains of adult toad
parotoid-gland-associated Gram-positive bacteria, Bacillus spp., were capable of
biotransforming secreted bufagenins, marinobufagenin (1), telocinobufagenin (2),
bufalin (3), and resibufagenin (4), to hydroxylated scaffolds commonly
encountered in cane toad eggs and tadpoles. Scaled-up cultivation, preparative
chromatography, and detailed spectroscopic analysis identified Bacillus sp. CMB
TD29 biotransformation products of 1, as 11alpha-hydroxymarinobufagenin (6),
12beta-hydroxymarinobufagenin (7), and 17alpha-hydroxymarinobufagenin (8).
Comparative bufagenin profiles across the cane toad life cycle suggest that
bacterial biotransformation mediates the oxidative adaptation of adult toad
bufagenins to hydroxylated bufagenins encountered in eggs and tadpoles. We
speculate that knowledge of a relationship between the cane toad microbiome and
bufagenin chemical defenses could inspire the development of a natural, nontoxic,
environmentally sustainable bacterial biocontrol for this toxic invasive species.
PMID- 28691814
TI - Intervention of Dietary Dipeptide Gamma-l-Glutamyl-l-Valine (gamma-EV)
Ameliorates Inflammatory Response in a Mouse Model of LPS-Induced Sepsis.
AB - Sepsis, the systemic inflammatory response syndrome (SIRS) with infection is one
of the leading causes of death in critically ill patients in the developed world
due to the lack of effective antisepsis treatments. This study examined the
efficacy of dietary dipeptide gamma-l-glutamyl-l-valine (gamma-EV), which was
characterized previously as an anti-inflammatory peptide, in an LPS-induced mouse
model of sepsis. BALB/c mice were administered gamma-EV via oral gavage followed
by an intraperitoneal injection of LPS to induce sepsis. The gamma-EV exhibited
antisepsis activity by reducing the expression of pro-inflammatory cytokines TNF
alpha, IL-6, and IL-1beta in plasma and small intestine. gamma-EV also reduced
the phosphorylation of the signaling proteins JNK and IkappaBalpha. We concluded
that gamma-EV could possess an antisepsis effect against bacterial infection in
intestine. This study proposes a signaling mechanism whereby the calcium-sensing
receptor (CaSR) allosterically activated by gamma-EV stimulates the interaction
of beta-arrestin2 with the TIR(TLR/IL-1R) signaling proteins TRAF6, TAB1, and
IkappaBalpha to suppress inflammatory signaling.
PMID- 28691815
TI - Facile Formation of Acetic Sulfuric Anhydride: Microwave Spectrum, Internal
Rotation, and Theoretical Calculations.
AB - Acetic sulfuric anhydride, CH3COOSO2OH, was produced by the reaction of SO3 and
CH3COOH in a supersonic jet. Four isotopologues were observed by microwave
spectroscopy. Spectra of both A and E internal rotor states were observed and
analyzed, yielding a value of 241.093(30) cm-1 for the methyl group internal
rotation barrier of the parent species. Similar values were obtained for the
other isotopologues studied. M06-2X/6-311++G(3df,3pd) calculations indicate that
the formation of the anhydride proceeds via a pi2 + pi2 + sigma2 cycloaddition
reaction within the CH3COOH-SO3 complex. The equilibrium orientation of the
methyl group relative to the O?C-C plane is different in the anhydride and in the
CH3COOH-SO3 complex, indicating that the -CH3 internal rotation accompanies the
cycloaddition reaction. The energies of key points on the potential energy
surface were calculated using CCSD(T)/complete basis set with double and triple
extrapolation [CBS/(D-T)], and the transformation from the CH3COOH-SO3 complex to
CH3COOSO2OH is shown to be nearly barrierless regardless of the orientation of
the methyl group. This study provides the second experimental observation of the
reaction between a carboxylic acid and SO3 to form a carboxylic sulfuric
anhydride in the gas phase. Possible connections to atmospheric aerosol formation
are discussed.
PMID- 28691816
TI - Mechanism of Excited-State Intramolecular Proton Transfer for 1,2
Dihydroxyanthraquinone: Effect of Water on the ESIPT.
AB - Mechanisms of excited-state intramolecular proton transfer (ESIPT) of 1,2
dihydroxyanthraquinone (ALR) in ethanol solvent and binary solvent of water and
ethanol are investigated using the density functional theory and time-dependent
density functional theory. The intramolecular hydrogen bond is found to be
reinforced in the excited state based on the bond lengths, bond angles, and
infrared vibrational spectra of relevant group. The reinforcement of
intramolecular hydrogen bond is attributed to the charge transfer in the excited
state, which leads the ESIPT to form a keto isomer. The absorption and
fluorescence spectra of ALR in binary solvent with different water percentage are
obtained and demonstrate the inhibition effect of water on the ESIPT process,
which are consistent with the experimentally observation. Furthermore, more water
molecules are considered near the carbonyl group and hydroxyl group related to
the intramolecular proton transfer to form intermolecular hydrated hydrogen bond
with ALR for clarifying the block mechanism of water on ESIPT. The potential
energy curves, frontier molecular orbitals, and NBO analysis are calculated for
the several complexes in the ground and excited states. The results show that the
interrupt role of water on the ESIPT originated from the forming of hydrated
hydrogen bond between the carbonyl oxygen atom and the water molecule, which
weakens the intramolecular hydrogen bond associated with proton transfer,
increases the energy barrier of ESIPT, and thus precludes the transition of ALR-E
to ALR-K in the excited state. In addition, the weakening of intramolecular
hydrogen bonds is increased as the water molecule number increases. So the
inhibitory effect is enhanced by the water quantity, which reasonably explains
the experimental attenuating of keto emission spectra as the water percentage in
binary solvent increases.
PMID- 28691817
TI - The Microwave Spectrum and Molecular Structure of (Z)-1-Chloro-2-Fluoroethylene
Acetylene: Demonstrating the Importance of the Balance Between Steric and
Electrostatic Interactions in Heterodimer Formation.
AB - The structure of the gas-phase heterodimer formed between (Z)-1-chloro-2
fluoroethylene and acetylene is determined via Fourier transform microwave
spectroscopy from 5.5 to 20.8 GHz. In the first instance where in the presence of
both a fluorine atom and a chlorine atom on the haloethylene the protic acid
binds to the chlorine atom, the acetylene adopts a configuration similar to that
in the analogous complex with vinyl chloride. Positioned in a manner to interact
favorably with both the chlorine atom and the hydrogen atom geminal to it, the
acetylene molecule is able to maximize the overall electrostatic stabilization
even though other regions of the haloethylene offer individual sites of greater
positive or negative electrostatic potential. Detailed comparison with the vinyl
chloride-acetylene complex suggests that the presence of the fluorine atom
weakens the hydrogen bond but strengthens the interaction between the geminal
hydrogen atom and the triple bond.
PMID- 28691818
TI - Copper(II) Binding Sites in N-Terminally Acetylated alpha-Synuclein: A
Theoretical Rationalization.
AB - The interactions between N-terminally acetylated alpha-synuclein and Cu(II) at
several binding sites have been studied with DFT calculations, specifically with
the M06 hybrid functional and the omegaB97X-D DFT-D functional. In previous
experimental studies, Cu(II) was shown to bind several alpha-synuclein residues,
including Met1-Asp2 and His50, forming square planar coordination complexes.
Also, it was determined that a low-affinity binding site exists in the C-terminal
domain, centered on Asp121. However, in the N-terminally acetylated protein,
present in vivo, the Met1 site is blocked. In this work, we simplify the
representation of the protein by modeling each experimentally found binding site
as a complex between an N-terminally acetylated alpha-synuclein dipeptide (or
several independent residues) and a Cu(II) cation, and compare the results with a
number of additional, structurally analogous sites not experimentally found. This
way of representing the binding sites, although extremely simple, allows us to
reproduce experimental results and to provide a theoretical rationale to explain
the preference of Cu(II) for certain sites, as well as explicit geometrical
structures for the complexes formed. These results are important to understand
the interactions between alpha-synuclein and Cu(II), one of the factors inducing
structural changes in the protein and leading to aggregated forms of it which may
play a role in neurodegeneration.
PMID- 28691819
TI - Photoelectron Velocity Map Imaging Spectroscopy of the Beryllium Sulfide Anion,
BeS.
AB - Slow electron velocity map imaging (SEVI) spectroscopy was used to examine the
BeS- anion to neutral ground-state transition, X 2Sigma+ -> X 1Sigma+. Rotational
constants, vibrational intervals, and the electron binding energy of BeS- were
determined. Partially resolved rotational contours were seen due to the
relatively small moment of inertia of beryllium sulfide. Upon analysis of the
rotational contours, it was found that changes in the molecular rotational
angular momentum, DeltaN = -1, -2, -3, and -4, facilitated photodetachment at
near-threshold photon energies. The electron affinity of BeS was found to be
2.3346(2) eV. SEVI spectra recorded using photon energies near the threshold for
Deltav = -1 processes exhibited features that were associated with a dipole-bound
state (DBS) of BeS-. Autodetachment spectroscopy was used to probe this state,
and rotationally resolved data were obtained for the DBS 2Sigma+, v' = 0 - X
2Sigma+, v" = 0 transition. Analysis of this structure provided the rotational
constants for BeS- X, v" = 0, and the electron binding energy of the DBS.
Electronic structure calculations, performed at the RCCSD(T) and MRCI levels of
theory, gave predictions that were in good agreement with the experimental
observations.
PMID- 28691820
TI - Oxidative [1,2]-Brook Rearrangements Exploiting Single-Electron Transfer:
Photoredox-Catalyzed Alkylations and Arylations.
AB - Oxidative [1,2]-Brook rearrangements via hypervalent silicon intermediates
induced by photoredox-catalyzed single-electron transfer have been achieved,
permitting the formation of reactive radical species that can engage in
alkylations and arylations.
PMID- 28691821
TI - In Situ Electron Driven Carbon Nanopillar-Fullerene Transformation through Cr
Atom Mediation.
AB - The promise of sp2 nanomaterials remains immense, and ways to strategically
combine and manipulate these nanostructures will further enhance their potential
as well as advance nanotechnology as a whole. The scale of these structures
requires precision at the atomic scale. In this sense electron microscopes are
attractive as they offer both atomic imaging and a means to structurally modify
structures. Here we show how Cr atoms can be used as physical linkers to connect
carbon nanotubes and fullerenes to graphene. Crucially, while under electron
irradiation, the Cr atoms can drive transformations such as catalytic healing of
a hole in graphene with simultaneous transformation of a single wall carbon
nanotube into a fullerene. The atomic resolution of the electron microscopy along
with density functional theory based total energy calculations provide insight
into the dynamic transformations of Cr atom linkers. The work augments the
potential of transmission electron microscopes as nanolaboratories.
PMID- 28691822
TI - Molecularly Imprinted Polymer Enables High-Efficiency Recognition and Trapping
Lithium Polysulfides for Stable Lithium Sulfur Battery.
AB - Using molecularly imprinted polymer to recognize various target molecules emerges
as a fascinating research field. Herein, we applied this strategy for the first
time to efficiently recognize and trap long-chain polysulfides (Li2Sx, x = 6-8)
in lithium sulfur battery to minimize the polysulfide shuttling between anode and
cathode, which enables us to achieve remarkable electrochemical performance
including a high specific capacity of 1262 mAh g-1 at 0.2 C and superior capacity
retention of over 82.5% after 400 cycles at 1 C. The outstanding performance is
attributed to the significantly reduced concentration of long-chain polysulfides
in electrolyte as evidenced by in situ UV/vis spectroscopy and Li2S nucleation
tests, which were further confirmed by density functional theory calculations.
The molecular imprinting is demonstrated as a promising approach to effectively
prevent the free diffusion of long-chain polysulfides, providing a new avenue to
efficiently recognize and trap lithium polysulfides for high-performance lithium
sulfur battery with greatly suppressed shuttle effect.
PMID- 28691823
TI - Reversible Monolayer-Bilayer Transition in Supported Phospholipid LB Films under
the Presence of Water: Morphological and Nanomechanical Behavior.
AB - Mixed monolayer Langmuir-Blodgett (LB) films of 1,2-dipalmitoyl-sn-glycero-3
phosphocholine (DPPC) and cholesterol (Chol) in the 1:1 ratio have been prepared
onto solid mica substrates. Upon immersion in water or in an aqueous HEPES
solution (pH 7.4) the monolayer LB films were spontaneously converted into well
organized bilayers leaving free mica areas. The process has been demonstrated to
be reversible upon removal of the aqueous solution, resulting in remarkably free
of defects monolayers that are homogeneously distributed onto the mica. In
addition, the nanomechanical properties exhibited by the as-formed bilayers have
been determined by means of AFM breakthrough force studies. The bilayers formed
by immersion of the monolayer in an aqueous media exhibit nanomechanical
properties and stability under compression analogous to those of DPPC:Chol
supported bilayers obtained by other methods previously described in the
literature. Consequently, the hydration of a monolayer LB film has been revealed
as an easy method to produce well-ordered bilayers that mimic the cell membrane
and that could be used as model cell membranes.
PMID- 28691824
TI - Sustained Sub-60 mV/decade Switching via the Negative Capacitance Effect in MoS2
Transistors.
AB - It has been shown that a ferroelectric material integrated into the gate stack of
a transistor can create an effective negative capacitance (NC) that allows the
device to overcome "Boltzmann tyranny". While this switching below the thermal
limit has been observed with Si-based NC field-effect transistors (NC-FETs), the
adaptation to 2D materials would enable a device that is scalable in operating
voltage as well as size. In this work, we demonstrate sustained sub-60 mV/dec
switching, with a minimum subthreshold swing (SS) of 6.07 mV/dec (average of 8.03
mV/dec over 4 orders of magnitude in drain current), by incorporating hafnium
zirconium oxide (HfZrO2 or HZO) ferroelectric into the gate stack of a MoS2 2D
FET. By first fabricating and characterizing metal-ferroelectric-metal
capacitors, the MoS2 is able to be transferred directly on top and characterized
with both a standard and a negative capacitance gate stack. The 2D NC-FET
exhibited marked enhancement in low-voltage switching behavior compared to the 2D
FET on the same MoS2 channel, reducing the SS by 2 orders of magnitude. A maximum
internal voltage gain of ~28* was realized with ~12 nm thick HZO. Several unique
dependencies were observed, including threshold voltage (Vth) shifts in the 2D NC
FET (compared to the 2D-FET) that correlate with source/drain overlap capacitance
and changes in HZO (ferroelectric) and HfO2 (dielectric) thicknesses. Remarkable
sub-60 mV/dec switching was obtained from 2D NC-FETs of various sizes and gate
stack thicknesses, demonstrating great potential for enabling size- and voltage
scalable transistors.
PMID- 28691825
TI - Small Molecule Recognition Triggers Secondary and Tertiary Interactions in DNA
Folding and Hammerhead Ribozyme Catalysis.
AB - We have identified tris(2-aminoethyl)amine (tren)-derived scaffolds with two
(t2M) or four (t4M) melamine rings that can target oligo T/U domains in DNA/RNA.
Unstructured T-rich DNAs cooperatively fold with the tren derivatives to form
hairpin-like structures. Both t2M and t4M act as functional switches in a family
of hammerhead ribozymes deactivated by stem or loop replacement with a U-rich
sequence. Catalysis of bond scission in these hammerhead ribozymes could be
restored by putative t2M/t4M refolding of stem secondary structure or tertiary
bridging interactions between loop and stem. The simplicity of the t2M/t4M
binding site enables programming of allostery in RNAs, recoding oligo-U domains
as potential sites for secondary structure or tertiary contact. In combination
with a facile and general method for installation of the t2M motif on primary
amines, the method described herein streamlines design of synthetic allosteric
riboswitches and small molecule-nucleic acid complexes.
PMID- 28691826
TI - Cu-Catalyzed Aminodifluoroalkylation of Alkynes and alpha
Bromodifluoroacetamides.
AB - The copper-catalyzed highly regioselective aminodifluoroalkylation of alkynes and
alpha-bromodifluoroacetamides was realized for the first time. With this method,
3,3-difluoro-1H-pyrrol-2(3H)-ones were constructed in a single step from various
alkynes and alpha-bromodifluoroacetamides substrates without using any extra
oxidant.
PMID- 28691827
TI - Understanding the Influence of [EMIM]Cl on the Suppression of the Hydrogen
Evolution Reaction on Transition Metal Electrodes.
AB - We have studied the influence of low concentrations (0.1 M) of the ionic liquid 1
ethyl-3-methylimidazolium chloride ([EMIM]Cl) on suppressing the hydrogen
evolution reaction (HER) using polycrystalline Ag, Cu, and Fe electrodes in
aqueous acidic and basic media. HER suppression is generally desired when aiming
to catalyze other reactions of interests, e.g., CO2 electro-reduction. Cyclic
voltammetry and chronoamperometry measurements were performed at potentials
between -0.2 and -0.8 V versus the reversible hydrogen electrode (RHE) to
investigate HER activity in a simulated CO2 electrolysis environment without the
CO2. In an acidic electrolyte, a decrease in HER activity was observed for all
three electrodes with the largest effect being that of Fe, where the HER activity
was suppressed by 75% at -0.5 V versus RHE. In contrast to the effect of [EMIM]Cl
in an acidic electrolyte, no HER suppression was observed in basic media. Using
1H nuclear magnetic resonance spectroscopy on the electrolyte before and after
electrolysis, it was determined that [EMIM]Cl breaks down at both the working and
counter electrodes under reaction conditions under both acidic and basic
conditions. These results underscore the challenges in employing ionic liquids
for electrochemical reactions such as CO2 reduction.
PMID- 28691828
TI - Virulence and antibiotic resistance genes in Campylobacter spp. in the Czech
Republic.
AB - OBJECTIVE: Thermotolerant species of the genus Campy-lobacter are the important
agents causing human foodborne infections throughout the world. The aims of this
study were to evaluate the presence of nine putative virulence genes in
Campylobacter spp. isolated from patients and from foods (poultry meat, pork
liver), to determine the resistance of Campylobacter isolates to eight antibiotic
agents and to detect four resistance genes.Matherial and methods: The presence of
the virulence genes cdtA, cdtB, cdtC, virB11, ciaB, wlaN, iam, dnaJ and racR was
detected by polymerase chain reaction (PCR) in 94 Campylobacter spp. isolates
from humans and 123 campylobacters from foods. The phenotypic resistance to
selected antimicrobial agents was tested with microdilution method in 82 human
isolates and 91 food isolates. The isolates with antibiograms were tested for the
presence of blaOXA-61, tet(O), aph-3-1 and cmeB genes by PCR with specific
primers. RESULTS: In both human and food C. jejuni isolates the preva-lence of
the studied virulence genes, especially dnaJ, racR, ciaB genes and the toxigenic
genes cdtA, cdtB, cdtC, was considerably higher than in C. coli isolates. The
only exception was the iam gene identified in only C. coli. The tested isolates
of both C. jejuni and C. coli were highly resistant to quinolone antibiotics.
Additionally, C. coli was also more resistant to erythromycin, streptomycin and,
in case of isolates from pork liver, to tetracycline. High prevalence rates of
genes encoding antibiotic resistance was noted for the blaOXA-61 and tet(O) genes
in both Campylobacter species. CONCLUSIONS: The presented study is the first to
assess the presence of genes for virulence and resistance to antibiotics in
thermotolerant Campylobacter spp. isolated from humans and foods in the Czech
Republic. The resistance of Campylobacter isolates to eight antibiotic agents was
also assessed. The prevalence of genes responsible for virulence and resistance
is rather varied in thermotolerant Campylobacter spp.
PMID- 28691829
TI - Sepsis-related mortality in the Czech Republic: multiple causes of death
analysis.
AB - AIM: Sepsis represents an increasingly frequent complication in the survival of
the hospitalized persons. The nation-wide burden of the sepsis-related mortality
in the Czech Republic has not yet been analysed. The present study aims to assess
the trends and the disparities in the sepsis-related mortality in the Czech
Republic for the period 1998-2011 using multiple causes of death reported on the
death certificates. MATERIALS AND METHODS: Individual death records provided by
the Institute for Health Information and Statistics were used to identify sepsis
related deaths based on the codes of the 10th revision of the International
classification of the diseases (ICD-10). Frequencies, age-standardized rates and
comorbidity patterns were studied. RESULTS: A total of 41,425 cases (3%) out of
1,456,539 deaths within the period 1998-2011 were associated with sepsis. In
2011, sepsis was reported in 8% of all in-hospital deaths. Sepsis is the most
likely to be reported as immediate cause of death (66%), which results in its
considerable underestimation in the underlying cause of death statistics. The
sepsis-related mortality almost tripled between 1998 and 2011, and the most of
the increase is attributable to persons aged 65 and over. In 44% of cases,
circulatory disease or cancer was reported as the underlying cause of death.
Significant associations with sepsis were however found for infectious diseases,
diseases of skin, and metabolic or musculoskeletal disorders. CONCLUSION:
Multiple cause of death analysis of sepsis-related mortality revealed that sepsis
represents a growing burden related to the population ageing and increased
prevalence of complications of chronic diseases. The observed upward trends, as
well as the expected continuation of the ageing process, may result in further
increase of sepsis-related mortality. Preventive measures in the clinical
management of sepsis are recommended.
PMID- 28691830
TI - The effect of adenotomy, allergy and smoking on microbial colonization of upper
aerodigestive tract in children.
AB - AIM: To evaluate microbial colonization of upper aerodigestive tract in children
and to investigate the influence of adenoid hypertrophy, allergy and exposition
to cigarette smoke on presence of pathogens. METHODS: In 43 children with adenoid
hypertrophy and 17 healthy children bacterial culture was performed by a swab
from middle nasal meatus, nasopharynx and tonsils. The effect of adenotomy,
presence of allergy and exposure to passive smoking on bacterial colonization
were investigated. RESULTS: Identification of potentially pathogenic bacteria in
upper aerodigestive tract was significantly higher in children with adenoid
hypertrophy compare to control group. Adenotomy was associated with significantly
decreased colonization by potential pathogens. Allergy was diagnosed in 33 %
children with adenoid hypertrophy. Presence of allergy and exposure to tobacco
smoke were associated with significantly more often colonization by potentially
pathogenic bacteria in the upper aerodigestive tract. CONCLUSION: Increased
colonization of upper aerodigestive tract by potential pathogens and their
significant decrease after adenotomy indicate the role of pathogenic bacteria in
the etiopathogenesis of adenoid hypertrophy. Allergy and tobacco smoke exposure
are related to increased colonization by potentially pathogenic bacteria in the
upper aerodigestive tract.
PMID- 28691831
TI - [Diagnostic relevance of the chemokine CXCL13 and anti-C6 peptide antibodies in
patients with neuroborreliosis].
AB - AIM OF THE STUDY: The study was focused on testing the diagnostic value of
detection of the chemokine CXCL13 (B lymphocyte chemoattractant) and anti-C6
peptide (synthetic peptide derived from B. burdorferi VlsE protein) antibodies in
patients with neuroborreliosis (NB). MATERIAL AND METHODS: One hundred and twenty
nine patients with clinical suspicion of neuroinfection were included in the
study. Eighty patients with NB (positive for antibodies in serum and CSF) were
subdivided into four groups (A1-A4) based on positivity/negativity of the
antibody index (AI) and pleocytosis. The control group was composed of 49
patients with a negative AI and absence of CSF pleocytosis. Chemokine CXCL13 and
anti-C6 antibodies were examined by commercial kits (Human CXCL13/BLC/BCA-1
Immunoassay, R&D Systems, INC, USA and C6 B. burgdorferi (Lyme) ELISA, Immunetics
Inc. USA). The CXCL13 cut-off values were set to 130 pg/ml for the CSF and 62
pg/ml for the serum. RESULTS: The highest CSF levels of CXCL13 chemokine were
found in group A1 (pleocytosis, AI positive), and they were significantly higher
(p < 0.001) comparing with other groups except A3 (pleocytosis, AI negative; p =
0.04). Group A3 also showed significantly higher levels of CXCL13 than groups A2
(without pleocytosis, AI positive; p = 0.005), A4 (without pleocytosis, AI
negative), and B (p < 0.001). The differences in the serum CXCL13 levels between
groups were non-significant. The serum anti-C6 antibodies were detected in all NB
groups and the positivity rates did not differ between groups (92%) except for A3
where 55% of the patients were positive. In the CSF, the highest anti-C6
sensitivity was found in the patients with a positive AI (A1 88.6%; A2 76.9%)
while in the groups with a negative AI, it was low (A3 25%; A4 0%). In group B,
anti-C6 antibodies were not detected. CONCLUSION: The highest CSF CXCL13 levels
were found in early stage NB. Elevated CXCL13 concentrations correlate better
with pleocytosis than with AI positivity; however, there exist some patients with
a positive AI who have low CXCL13 levels. These patients are most probably those
in the late - subacute stage of neuroinfection. The CXCL13 testing seems to be
the most diagnostically helpful in the acute stage of NB where AI is still
negative. The clinical sensitivity of the C6 ELISA test appears to be
insufficient for CSF examination under our conditions. On the contrary, the
specificity of this test was proven high, because none of the controls tested
positive.
PMID- 28691832
TI - [Identification of bacteria from blood cultures by fluorescence in situ
hybridization].
AB - The diagnosis of bacterial agents of sepsis from blood cultures is crucial for
the subsequent treatment of this condition. The aim of this study was to compare
Gram stain, culture, and biochemical identification (conventional methods) and
fluorescence in-situ hybridisation (FISH) that detects microorganisms from
positive blood cultures using specific probes. Another aim was to evaluate the
potential of this method for use in clinical practice. Altogether 71 samples of
positive blood cultures were tested by FISH. Blood cultures were also processed
in the conventional way using the BACTEC analyser. The bacteria recovered were
inoculated on solid media and then identified biochemically. The results obtained
by the conventional methods and HemoFISH were not 100% concordant. The
sensitivity of HemoFISH was 90.1%. Very good results were achieved for
staphylococci and enterobacteria. FISH identification failed in three cases
because the hybridization probes were not able to bind to bacterial rRNA. The
FISH bacterial identification is faster than the conventional methods, but should
be confirmed by the latter.
PMID- 28691833
TI - [The common bed bug (Cimex lectularius) - biology, medical relevance,
possibilities for the detection and control].
AB - Bed bugs have become a major concern worldwide in the 21st century and are
therefore intensively investigated. The new findings not only extend the
knowledge of their biology, medical relevance, and causes of the resurgence, but
also can be used in bed bug management. A brief overview is provided of some of
the most important research results and opinions, published in the last few years
in prestigious international journals.
PMID- 28691834
TI - [Cat scratch disease - a neglected zoonosis].
AB - Cat scratch disease is a relatively rare infection that is caused by the
bacterium Bartonella henselae. This disease occurs after cat scratch or bite. The
course of the disease depends on the patients immunity status. In immunocompetent
patients, the disease typically runs as a lymph node syndrome. Sometimes, mild
general symptoms may appear, or the course can be atypical with a more serious
clinical manifestation involving various organs. In immunocompromised patients,
Bartonella henselae can cause bacillary angiomatosis or peliosis with a severe
course.
PMID- 28691835
TI - Agency before action: The application of behavioral activation in psychotherapy
with persons with psychosis.
AB - Incorporating behavioral activation into psychotherapy with persons with
psychosis requires adaptation in its conceptualization and application owing to
special deficits in the self-experience. Persons with psychosis often experience
a diminished or disorganized sense of self, and have deficits in coherently
narrating the experience of the self and in the ability to make sense of how to
take action and direct their own lives. Based on a metacognitive model of
disability in psychosis, the current paper presents a therapy process of a woman
coping with schizophrenia using Metacognitive Reflection and Insight Therapy
(Lysaker and Dimaggio, 2014) in the framework of an intersubjective model for
psychotherapy with persons with psychosis presented by Hasson-Ohayon, Kravetz,
and Lysaker (2016a). The case in point and its following discussion highlight the
important significance of metacognitive encouragement as a first step of
behavioral activation. (PsycINFO Database Record
PMID- 28691836
TI - The cost of empathy: Parent-adolescent conflict predicts emotion dysregulation
for highly empathic youth.
AB - Empathy plays a key role in maintaining close relationships and promoting
prosocial conflict resolution. However, research has not addressed the potential
emotional cost of adolescents' high empathy, particularly when relationships are
characterized by more frequent conflict. The present 6-year longitudinal study (N
= 467) investigated whether conflict with parents predicted emotion dysregulation
more strongly for high-empathy adolescents than for lower-empathy adolescents.
Emotion dysregulation was operationalized at both the experiential level, using
mood diary data collected for 3 weeks each year, and at the dispositional level,
using annual self-report measures. In line with predictions, we found that more
frequent adolescent-parent conflict predicted greater day-to-day mood variability
and dispositional difficulties in emotion regulation for high-empathy
adolescents, but not for average- and low-empathy adolescents. Mood variability
and difficulties in emotion regulation, in turn, also predicted increased
conflict with parents. These links were not moderated by empathy. Moreover, our
research allowed for a novel investigation of the interplay between experiential
and dispositional emotion dysregulation. Day-to-day mood variability predicted
increasing dispositional difficulties in emotion regulation over time, which
suggests that experiential dysregulation becomes consolidated into dispositional
difficulties in emotion regulation. Moderated mediation analyses revealed that,
for high-empathy adolescents, conflict was a driver of this dysregulation
consolidation process. Finally, emotion dysregulation played a role in overtime
conflict maintenance for high-empathy adolescents. This suggests that, through
emotion dysregulation, high empathy may paradoxically also contribute to
maintaining negative adolescent-parent interactions. Our research indicates that
high empathy comes at a cost when adolescent-parent relationships are
characterized by greater negativity. (PsycINFO Database Record
PMID- 28691837
TI - Childhood maltreatment and context dependent empathic accuracy in adult romantic
relationships.
AB - OBJECTIVES: Childhood maltreatment, that is neglect and abuse, are associated
with difficulties in adult relationship functioning. We tested whether childhood
maltreatment changes the presence of a relationship protective mechanism, called
motivated inaccuracy. It describes a decrease in romantic couples' empathic
accuracy, (EA), that is, their correct understanding of the partners' thoughts
and feelings, in situations that pose a potential threat to the stability of the
relationship. With this, couples seem to protect their relationship stability
from their partners' potentially destabilizing mental contents. METHOD: Romantic
couples were videotaped while discussing (a) their favorite film-genre
(neutral/positive), (b) their most relevant fear of the past year (personally
threatening), and (c) a reason that might lead to a break-up in their
relationship (relationship-threatening). EA was measured by the overlap between
participants' judgments of their partners' feelings and the partners' self-rated
actual feeling, using a continuous video rating of the interactions. Childhood
neglect and abuse were retrospectively assessed by a questionnaire. RESULTS:
Overall, participants decreased their EA for each other in the relationship
threatening versus personally threatening conversation, replicating motivated
inaccuracy. However, when individuals with high levels of reported childhood
neglect felt threatened by the relationship-threatening condition, they did not
show this relationship protective mechanism, that is, they showed maintained EA
scores. Abuse in childhood did not influence the presence of motivated
inaccuracy. CONCLUSIONS: Childhood neglect might influence adult romantic
relationship functioning by leading to a lack of motivated inaccuracy during
relationship-threatening situations. An altered threat coping strategy might
cause the inability to protect oneself from relationship-threatening information.
(PsycINFO Database Record
PMID- 28691838
TI - Boys do(n't) cry: Addressing the unmet mental health needs of African American
boys.
AB - If African American boys are contemplating taking their lives at early ages, the
hope for future generations is challenging at best. What is going on in African
American communities that there is a lack of safe spaces for boys to express
their emotions and to share their travails with supportive networks in lieu of
ending their lives? The situation of African American boys (ages 5-11) committing
suicide at higher levels-more than any other group-and the recent studies
regarding the rising rates of suicide among African American adolescent boys (12
and older) call for greater reflection and more discourse around the mental
health challenges faced by this group. We must identify the emotional and
psychological reasons that underlie suicidal behaviors for African American boys
and work to provide immediate intervention. Families, educators, and community
workers play key roles in identifying signs of mental health challenges such as
depression and connecting African American boys to mental health care services.
In this article, the authors discuss specific ways to better support boys who
exhibit early signs of depression and suicidal behavior. Topics discussed include
(1) untreated depression among African American youth; (2) looking deeper at the
reasons for untreated depression; (3) misunderstanding and denial of mental
health challenges; (4) risk factors in schools; (5) harsh discipline practices;
(6) low teacher expectations; and (7) disconnection from adults. (PsycINFO
Database Record
PMID- 28691839
TI - Introduction to the special section: Why we should highlight the outstanding
contributions of young investigators in the field of eating disorders.
AB - This introduction presents the context in which the Journal of Abnormal
Psychology created a special section to highlight outstanding contributions by
young investigators in the field of eating disorders. The first motivating factor
relates to our field's approach to mentoring and supporting its next generation
of researchers. The second motivating factor addresses a broader need to ensure
that the Journal of Abnormal Psychology remains an outlet in which this and
future generations share their innovative and important work. (PsycINFO Database
Record
PMID- 28691840
TI - Eating disorder-specific risk factors moderate the relationship between negative
urgency and binge eating: A behavioral genetic investigation.
AB - Theoretical models of binge eating and eating disorders include both
transdiagnostic and eating disorder-specific risk factors. Negative urgency
(i.e., the tendency to act impulsively when distressed) is a critical
transdiagnostic risk factor for binge eating, but limited research has examined
interactions between negative urgency and disorder-specific variables.
Investigating these interactions can help identify the circumstances under which
negative urgency is most strongly associated with binge eating. We examined
whether prominent risk factors (i.e., appearance pressures, thin-ideal
internalization, body dissatisfaction, dietary restraint) specified in well
established etiologic models of eating disorders moderate negative urgency-binge
eating associations. Further, we investigated whether phenotypic moderation
effects were due to genetic and/or environmental associations between negative
urgency and binge eating. Participants were 988 female twins aged 11-25 years
from the Michigan State University Twin Registry. Appearance pressures, thin
ideal internalization, and body dissatisfaction, but not dietary restraint,
significantly moderated negative urgency-binge eating associations, with high
levels of these risk factors and high negative urgency associated with the
greatest binge eating. Twin moderation models revealed that genetic, but not
environmental, sharing between negative urgency and binge eating was enhanced at
higher levels of these eating disorder-specific variables. Future longitudinal
research should investigate whether eating disorder risk factors shape genetic
influences on negative urgency into manifesting as binge eating. (PsycINFO
Database Record
PMID- 28691841
TI - Shared familial risk between bulimic symptoms and alcohol involvement during
adolescence.
AB - Twin studies show the established relation between bulimic symptoms and
problematic alcohol involvement in adult females is partly due to shared familial
factors, specifically shared genetic effects. However, it is unclear if similar
shared etiological factors exist during adolescence or in males. We examined the
familial overlap (i.e., genetic and common environmental correlations) between
bulimic symptoms and various levels of alcohol involvement in 16- to 17-year-old
female and male same-sex twin pairs using sex-specific biometrical twin modeling.
Bulimic symptoms were assessed with the Eating Disorder Inventory-2. Alcohol
involvement included alcohol use in the last month, having ever been intoxicated,
and alcohol intoxication frequency. Results revealed 3 distinct patterns. First,
in general, phenotypic correlations indicated statistically similar associations
between bulimic symptoms and alcohol involvement in girls and boys. Second,
common environmental overlap was significant for the bivariate associations
including having ever been intoxicated. Third, moderate genetic correlations were
observed between all bulimic symptoms and alcohol involvement in girls and
moderate common environmental correlations were observed in boys for the more
risky/deviant levels of involvement. Similar to adults, there is familial overlap
between bulimic symptoms and alcohol involvement in adolescent girls and boys.
These results could inform symptom- and sex-specific, developmentally targeted
prevention and intervention programs for the comorbidity between bulimic symptoms
and alcohol involvement. (PsycINFO Database Record
PMID- 28691842
TI - Response in taste circuitry is not modulated by hunger and satiety in women
remitted from bulimia nervosa.
AB - Individuals with bulimia nervosa (BN) engage in episodes of binge eating, marked
by loss of control and eating despite fullness. Does altered reward and metabolic
state contribute to BN pathophysiology? Normally, hunger increases (and satiety
decreases) reward salience to regulate eating. We investigated whether BN is
associated with an abnormal response in a neural circuit involved in translating
taste signals into motivated behavior, when hungry and fed. Twenty-six women
remitted from BN (RBN) and 22 control women (CW) were administered water and
sucrose during 2 counterbalanced fMRI visits, following a 16-hr fast or a
standardized breakfast. Significant Group * Condition interactions were found in
the left putamen, insula, and amygdala. Post hoc analyses revealed CW were
significantly more responsive to taste stimuli when hungry versus fed in the left
putamen and amygdala. In contrast, RBN response did not differ between
conditions. Further, RBN had greater activation in the left amygdala compared
with CW when fed. Findings suggest that RBN neural response to rewarding stimuli
may not be modulated by metabolic state. Data raise the possibility that
disinhibited eating in BN could result from a failure to devalue food reward when
fed, resulting in an exaggerated response. (PsycINFO Database Record
PMID- 28691843
TI - Associations of borderline personality disorder traits with stressful events and
emotional reactivity in women with bulimia nervosa.
AB - Borderline personality disorder (BPD) traits are common among those with bulimia
nervosa (BN). However, how these traits impact the state experience of
precipitants of BN behavior, such as stressful events and emotional reactivity,
has not been determined. Thus, the purpose of this naturalistic study was to
examine this trait-state association in BN. Women with DSM-IV BN (N = 133)
completed a baseline measure of personality pathology traits, and subsequently
recorded their affective state and the frequency and perception of 3 types of
stressful events (interpersonal, work/environment, and daily hassles) several
times per day for 2 weeks using ecological momentary assessment (EMA). Pearson
correlations assessed the associations between BPD traits (affective lability,
identity problems, insecure attachment, and cognitive dysregulation) and (a)
frequency of stressful events and (b) perception of stressful events. Generalized
linear models (GLM) were used to evaluate the relationship between BPD traits and
changes in negative affect following stressful events. Results revealed that
while all traits were significantly associated with perceived stressfulness,
certain BPD traits were significantly associated with the frequency of stressful
events. Individuals with higher trait insecure attachment experienced larger
increases in negative affect following interpersonal stressful events. These
findings suggest that interventions focused on addressing stressful events and
enhancing adaptive emotional responses to interpersonal events may be
particularly useful for a subset of individuals with BN with BPD-related
personality characteristics, including insecure attachment, affective lability,
and identity problems. (PsycINFO Database Record
PMID- 28691844
TI - The impact of acute stress on the neural processing of food cues in bulimia
nervosa: Replication in two samples.
AB - The impact of acute stress on the neural processing of food cues in bulimia
nervosa (BN) is unknown, despite theory that acute stress decreases cognitive
control over food and hence increases vulnerability to environmental triggers for
binge eating. Thus, the goals of this manuscript were to explore the impact of
acute stress on the neural processing of food cues in BN. In Study 1, 10 women
with Diagnostic and Statistical Manual of Mental Disorders (5th ed.; DSM-5;
American Psychiatric Association, 2013) BN and 10 healthy controls participated
in an fMRI paradigm examining the neural correlates of visual food cue processing
pre and post an acute stress induction. Whole brain analysis indicated that women
with BN exhibited significant decreases in activation in the precuneus,
associated with self-referential processing, the paracingulate gyrus, and the
anterior vermis of the cerebellum. Healthy controls exhibited increased
activation in these regions in response to food cues poststress. In Study 2, 17
women with DSM-5 BN or otherwise specified feeding and eating disorder with BN
symptoms participated in the same paradigm. A region of interest analysis
replicated findings from Study 1. Replication of imaging findings in 2 different
samples suggests the potential importance of these regions in relation to BN.
Decreased activation in the precuneus, specifically, is consistent with models of
BN that posit that binge eating serves as a concrete distraction from aversive
internal stimuli. (PsycINFO Database Record
PMID- 28691845
TI - Maternal eating disorders and perinatal outcomes: A three-generation study in the
Norwegian Mother and Child Cohort Study.
AB - Previous studies of the relationship between maternal eating disorders and
adverse perinatal outcomes have failed to control for familial transmission of
perinatal phenotypes, which may confound the reported association. In a unique
design afforded by the Norwegian Mother and Child Cohort Study and Medical Birth
Registry of Norway, we linked three generations through birth register records
and maternal-reported survey data to investigate whether maternal eating
disorders increase risk after parsing out the contribution of familial
transmission of perinatal phenotypes. The samples were 70,881 pregnancies in
grandmother-mother-child triads for analyses concerning eating disorder exposure
during pregnancy and 52,348 for analyses concerning lifetime maternal eating
disorder exposure. As hypothesized, eating disorders predicted a higher incidence
of perinatal complications even after adjusting for grandmaternal perinatal
phenotypes. For example, anorexia nervosa immediately prior to pregnancy was
associated with smaller birth length (relative risk = 1.62; 95% CI [1.20, 2.14]),
bulimia nervosa with induced labor (relative risk = 1.21; 95% CI [1.07, 1.36]),
and binge-eating disorder with several delivery complications, larger birth
length (relative risk = 1.25; 95% CI [1.17, 1.34]), and large-for-gestational-age
(relative risk = 1.04; 95% CI [1.01, 1.06]). Maternal pregravid body mass index
and gestational weight mediated most associations. Our results support that
exposure to eating disorders increases the risk for negative health outcomes in
pregnant women and their babies. (PsycINFO Database Record
PMID- 28691846
TI - A review of purging disorder through meta-analysis.
AB - Although a growing body of research has examined Purging Disorder (PD), there
remains a lack of conclusive evidence regarding the diagnostic validity of PD.
This meta-analysis compared PD to DSM-5 eating disorders (i.e., Anorexia Nervosa
[AN], Bulimia Nervosa [BN], and Binge Eating Disorder [BED]) and controls. A
comprehensive literature search identified 38 eligible studies. Group differences
on indicators of course of illness and both general and eating psychopathology
were assessed using standardized effect sizes. Results supported the
conceptualization of PD as a clinically significant eating disorder, but findings
were less clear regarding its distinctiveness from other eating disorder
diagnoses. More specifically, PD significantly differed from BN and BED in
natural course of illness (g = .40-.54), and PD significantly differed from AN in
treatment outcome (g = .27), with PD characterized by a better prognosis.
Overall, PD was more similar to AN and BED on many dimensional measures of
general and eating-related psychopathology, though PD was less severe than BN in
most of these domains. PD, BN, and BED groups also evidenced similar frequencies
of subjective binge episodes (SBEs), yet PD evidenced less frequent SBEs than AN.
There is a clear need for future studies of PD to assess validators that have not
been reported comprehensively in the literature, such as mortality, medical
morbidity, and course of illness. Additionally, empirical classification studies
are needed to inform future classifications of PD, particularly with regard to
categorical differences between PD and other eating disorders. (PsycINFO Database
Record
PMID- 28691847
TI - Expanding the developmental boundaries of etiologic effects: The role of
adrenarche in genetic influences on disordered eating in males.
AB - Genetic influences on disordered eating (DE) increase across age and puberty in
girls, an effect that is at least partially due to ovarian hormone activation.
However, development shifts in genetic effects have not been detected in boys;
genetic influences have been found to be relatively constant from prepuberty to
adulthood, suggesting that gonadal hormones may be less important. One caveat is
that studies have examined males ages 10 or older. Genetic effects on DE may
emerge earlier in boys, such as during adrenarche, when androgens begin to
increase but the physical changes of puberty are not yet observable. The current
study investigated this hypothesis in 1,212 male twins (ages 6-28) from the
Michigan State University Twin Registry. Results supported a potential role of
adrenarche, as genetic influences on DE increased during middle childhood, prior
to the external physical changes of puberty. Specifically, genetic influences on
DE were negligible (0%) in twins during pre- to early adrenarche, but increased
incrementally across advancing adrenarche (17% to 44%) and into early puberty
(57%). Genetic effects then remained stable into midpuberty and postpuberty
(58%), suggesting that nearly all of the genetic effects on DE become prominent
during adrenarche in males. Findings suggest that genetic effects on DE emerge
sooner in boys than the midpubertal activation that is consistently found in
girls. These data highlight a potentially important role for adrenarche in the
genetic diathesis for DE in males and a need to examine younger ages in studies
of developmental effects. (PsycINFO Database Record
PMID- 28691848
TI - Contributions from outstanding young eating disorder investigators: What we are
learning, how we are learning it, and where might we go next?
AB - This is a time of striking progress in the field of eating disorders, and
outstanding young psychological scientists are playing an important role in this
progress. This special section provides a sample of this work, which is
characterized by a diversity of research questions and methods. The importance of
transdiagnostic processes that increase risk for both disordered eating and other
dysfunction is reflected in articles that identify shared familial risk across
disorders, integrate transdiagnostic and eating disorder-specific risk, and
examine the impact of affective processing on restricting behavior. The
importance of eating disorder-specific risk is reflected in an article on
disorder-specific relations between hunger and taste. The importance of
integrative risk models across levels of analysis is reflected in articles that
investigate the heritable component of interactions between broad personality and
disorder-specific risk factors, the momentary impact of personality traits on
precipitants of binge-purge episodes, brain system function responses to
environmental stressors, and cross-generational transmission of risk. The
importance of further understanding the nature and scope of eating disorder
pathology is reflected in a meta-analysis of purging disorder and an
investigation of genetic effects on disordered eating in males. This commentary
places these articles in the context of challenges facing the field and considers
the future of eating disorders research. (PsycINFO Database Record
PMID- 28691849
TI - Electrophysiological evidence for detrimental impact of a reappraisal emotion
regulation strategy on subsequent cognitive control in schizophrenia.
AB - In healthy individuals, there is evidence that effective implementation of an
emotion regulation strategy has beneficial effects on temporally proximal
cognitive control task performance. This effect occurs because both of these
processes rely heavily on the prefrontal cortex. Individuals with schizophrenia
(SZ) have impairments in both emotion regulation and cognitive control that are
driven by structural and functional abnormalities of the prefrontal cortex;
however, it is unknown whether emotion regulation attempts fail to benefit
subsequently performed cognitive control tasks in people with SZ. The present
study examined whether attempts to increase or decrease negative emotion via
reappraisal have differential effects on subsequent cognitive control in a sample
of outpatients diagnosed with SZ (n = 30) and demographically matched healthy
controls (CN; n = 29). Participants completed a combined emotion regulation and
cognitive control task in which numerical Stroop trials were presented
immediately after unpleasant or neutral images that were either increased via
reappraisal, decreased via reappraisal, or passively viewed. The
electroencephalogram was recorded while participants performed the reappraisal
Stroop task and event related potentials (ERPs) were used to index emotion
regulation effectiveness (late positive potential: LPP) and cognitive control
(sustained potential: SP). Both CN and SZ evidenced higher LPP amplitude for
unpleasant than neutral stimuli consistent with robust neural response to
unpleasant stimuli. Although CN demonstrated neurophysiological evidence of
effective use of reappraisal to increase and decrease negative emotion, SZ only
showed an effective ability to increase negative emotion via reappraisal. CN
displayed enhanced cognitive control following increase trials and impaired
cognitive control following decrease trials, as indicated by modulation of SP
amplitude. In SZ, increase instructions impaired cognitive control and decrease
instructions had no effect on cognitive control. Findings suggest that emotion
regulation abnormalities may play an underrecognized role in general cognitive
control deficits that occur in SZ. (PsycINFO Database Record
PMID- 28691850
TI - "Default mode functional connectivity is associated with social functioning in
schizophrenia": Correction to Fox et al. (2017).
AB - Reports an error in "Default mode functional connectivity is associated with
social functioning in schizophrenia" by Jaclyn M. Fox, Samantha V. Abram, James
L. Reilly, Shaun Eack, Morris B. Goldman, John G. Csernansky, Lei Wang and
Matthew J. Smith (Journal of Abnormal Psychology, 2017[May], Vol 126[4], 392
405). In the article, the email address of corresponding author Matthew J. Smith
was set as matthewsmith@northwestern.edu. It should have been mattjsmi@umich.edu.
The online version of this article has been corrected. (The following abstract of
the original article appeared in record 2017-14073-001.) Individuals with
schizophrenia display notable deficits in social functioning. Research indicates
that neural connectivity within the default mode network (DMN) is related to
social cognition and social functioning in healthy and clinical populations.
However, the association between DMN connectivity, social cognition, and social
functioning has not been studied in schizophrenia. For the present study, the
authors used resting-state neuroimaging data to evaluate connectivity between the
main DMN hubs (i.e., the medial prefrontal cortex [mPFC] and the posterior
cingulate cortex-anterior precuneus [PPC]) in individuals with schizophrenia (n =
28) and controls (n = 32). The authors also examined whether DMN connectivity was
associated with social functioning via social attainment (measured by the
Specific Levels of Functioning Scale) and social competence (measured by the
Social Skills Performance Assessment), and if social cognition mediates the
association between DMN connectivity and these measures of social functioning.
Results revealed that DMN connectivity did not differ between individuals with
schizophrenia and controls. However, connectivity between the mPFC and PCC hubs
was significantly associated with social competence and social attainment in
individuals with schizophrenia but not in controls as reflected by a significant
group-by-connectivity interaction. Social cognition did not mediate the
association between DMN connectivity and social functioning in individuals with
schizophrenia. The findings suggest that fronto-parietal DMN connectivity in
particular may be differentially associated with social functioning in
schizophrenia and controls. As a result, DMN connectivity may be used as a
neuroimaging marker to monitor treatment response or as a potential target for
interventions that aim to enhance social functioning in schizophrenia. (PsycINFO
Database Record
PMID- 28691851
TI - Initiation, dropout, and outcome from evidence-based psychotherapies in a VA PTSD
outpatient clinic.
AB - Trauma-focused, evidence-based psychotherapies (TF-EBPs) for posttraumatic stress
disorder (PTSD) have been widely promoted in the Veterans Health Administration
to provide access to state-of-the-art treatments, but dropout rates may affect
the impact of TF-EBPs. The current study summarizes findings from a program
evaluation of 67 veterans assigned to trauma-focused treatment in a Veterans
Affairs outpatient PTSD clinic. Outcomes of interest include attendance rates,
dropout rates and patterns, treatment paths, changes in self-reported symptoms,
and clinician ratings. Nine veterans (13.4%) did not attend a first session and
15 (22.4%) dropped out before session 4. Twenty-three (33.8%) received either a
modified version of the TF-EBP or switched to a different treatment. Only 11
(16.4%) completed the assigned TF-EBP, but 10 of those 11 (90.9%) were rated by
their therapist as improved. These results align with previous research
documenting high dropout rates from PTSD treatment in veterans and substantial
improvements for those who complete TF-EBPs. Future study of methods to enhance
retention in TF-EBP treatments is needed. (PsycINFO Database Record (c) 2018 APA,
all rights reserved).
PMID- 28691852
TI - The Importance of Interactions at the Molecular Level: A Spectroscopic Study of a
New Composite Sorber Material.
AB - The functional properties of a new composite material having water vapor getter
properties have been investigated by a large arsenal of characterization
techniques. The composite system is originated by combining two constituents
having very different chemical natures, a magnesium perchlorate (Mg(ClO4)2) salt
and a polymeric acrylic matrix. In particular, Fourier transform infrared (FT-IR)
and Raman spectroscopy have been fundamental to understand the type of
interactions between the salt and the matrix in different hydration conditions.
It was found that in the anhydrous composite system the dispersed Mg(ClO4)2 salt
retains its molecular structure, because Mg2+ cations are still surrounded by
their [ClO4]- counter-anions; at the same time, the salt and the polymeric matrix
chemically interact each other at the molecular level. These interactions
gradually vanish in the presence of water, and disappear in the fully hydrated
composite system, where the Mg2+ cations are completely solvated by the water
molecules.
PMID- 28691853
TI - Assessment of Cardiac Autonomic Tone Following Long Sudarshan Kriya Yoga in Art
of Living Practitioners.
AB - OBJECTIVE: The breathing processes are known to modulate cardiac autonomic tone
and improve psychological status. We investigated cardiac autonomic tone
following long Sudarshan Kriya Yoga (SKY) using heart rate variability (HRV) and
skin conductance level (SCL). METHODS: Thirty healthy volunteers (age 28.3 +/-
8.4 years; 23 M: 7 F) participated in the study. Electrocardiogram (ECG) and SCL
were recorded for 5 min each, before and after long SKY. Long SKY is a
combination of pranayama and cyclic rhythmic breathing and is performed by
following the guided audio instructions. HRV analysis was used for the assessment
of cardiac autonomic tone. Time and frequency domain parameters of HRV were
calculated by using RR interval of ECG. SCL was acquired using Galvanic skin
response (GSR) amplifier of PowerLab in microSeimens (MUS). RESULTS: Time domain
parameters of HRV, including mean RR interval (p = 0.000), respiratory sinus
arrhythmia (RSA) (p = 0.037), standard deviation of all NN intervals (SDNN) (p =
0.013), NN50 count divided by the total number of all NN intervals (pNN50) (p =
0.004), and square root of the mean of the sum of the squares of differences
between adjacent NN intervals (RMSSD) (p = 0.002) increased, and mean heart rate
decreased (p = 0.000) following long SKY. In frequency domain analysis, power of
low-frequency (LF) component (p = 0.010) and LF/HF ratio (p = 0.008) decreased
significantly, whereas power of high frequency (HF) significantly increased (p =
0.010). SCL decreased following long SKY, although it did not attain statistical
significance. CONCLUSIONS: The results suggest that long SKY induces significant
oscillations in cardiac autonomic tone. Parasympathetic activity increases and
sympathetic activity decreases and sympathovagal balance improves following long
SKY. Decrease in sympathetic activity is also demonstrated by decrease in
conductance although it did not reach statistical significance. From this study
it can be concluded that long SKY has a beneficial effect on cardiac autonomic
tone, and psychophysiological relaxation. It may serve as a tool to improve HRV,
which is the marker of cardiovascular health.
PMID- 28691854
TI - Impact of Gamification of Vision Tests on the User Experience.
AB - OBJECTIVE: Gamification has been incorporated into vision tests and vision
therapies in the expectation that it may increase the user experience and
engagement with the task. The current study aimed to understand how gamification
affects the user experience, specifically during the undertaking of
psychophysical tasks designed to estimate vision thresholds (chromatic and
achromatic contrast sensitivity). METHODS: Three tablet computer-based games were
developed with three levels of gaming elements. Game 1 was designed to be a
simple clinical test (no gaming elements), game 2 was similar to game 1 but with
added gaming elements (i.e., feedback, scores, and sounds), and game 3 was a
complete game. Participants (N = 144, age: 9.9-42 years) played three games in
random order. The user experience for each game was assessed using a Short
Feedback Questionnaire. RESULTS: The median (interquartile range) fun level for
the three games was 2.5 (1.6), 3.9 (1.7), and 2.5 (2.8), respectively. Overall,
participants reported greater fun level and higher preparedness to play the game
again for game 2 than games 1 and 3 (P < 0.05). There were significant positive
correlations observed between fun level and preparedness to play the game again
for all the games (p < 0.05). Engagement (assessed as completion rates) did not
differ between the games. CONCLUSION: Gamified version (game 2) was preferred to
the other two versions. Over the short term, the careful application of gaming
elements to vision tests was found to increase the fun level of users, without
affecting engagement with the vision test.
PMID- 28691855
TI - In Situ Raman Spectral Characteristics of Carbon Dioxide in a Deep-Sea Simulator
of Extreme Environments Reaching 300 C and 30 MPa.
AB - Deep-sea carbon dioxide (CO2) plays a significant role in the global carbon cycle
and directly affects the living environment of marine organisms. In situ Raman
detection technology is an effective approach to study the behavior of deep-sea
CO2. However, the Raman spectral characteristics of CO2 can be affected by the
environment, thus restricting the phase identification and quantitative analysis
of CO2. In order to study the Raman spectral characteristics of CO2 in extreme
environments (up to 300 C and 30 MPa), which cover most regions of hydrothermal
vents and cold seeps around the world, a deep-sea extreme environment simulator
was developed. The Raman spectra of CO2 in different phases were obtained with
Raman insertion probe (RiP) system, which was also used in in situ Raman
detection in the deep sea carried by remotely operated vehicle (ROV) "Faxian".
The Raman frequency shifts and bandwidths of gaseous, liquid, solid, and
supercritical CO2 and the CO2-H2O system were determined with the simulator. In
our experiments (0-300 C and 0-30 MPa), the peak positions of the symmetric
stretching modes of gaseous CO2, liquid CO2, and supercritical CO2 shift
approximately 0.6 cm-1 (1387.8-1388.4 cm-1), 0.7 cm-1 (1385.5-1386.2 cm-1), and
2.5 cm-1 (1385.7-1388.2 cm-1), and those of the bending modes shift about 1.0 cm
1 (1284.7-1285.7 cm-1), 1.9 cm-1 (1280.1-1282.0 cm-1), and 4.4 cm-1 (1281.0
1285.4 cm-1), respectively. The Raman spectral characteristics of the CO2-H2O
system were also studied under the same conditions. The peak positions of
dissolved CO2 varied approximately 4.5 cm-1 (1282.5-1287.0 cm-1) and 2.4 cm-1
(1274.4-1276.8 cm-1) for each peak. In comparison with our experiment results,
the phases of CO2 in extreme conditions (0-3000 m and 0-300 C) can be identified
with the Raman spectra collected in situ. This qualitative research on CO2 can
also support the further quantitative analysis of dissolved CO2 in extreme
conditions.
PMID- 28691856
TI - Chemical constituents from the leaves of Pinus dalatensis Ferre.
AB - A phytochemical study of n-hexane and ethyl acetate extracts of Pinus dalatensis
Ferre leaves led to the isolation of 11 compounds, including one caryolane
sesquiterpenoid (1), five labdane diterpenoids (2, 3, 4, 5, 6), one serratane
triterpenoid (7), one diacylated flavonoid glucoside (8), one stilbenoid (9) and
two sterols (10, 11). The structural characterisation of the isolated compounds
was elucidated by spectroscopic data and comparison with the literature report on
the chemical constituents from Pinus dalatensis Ferre. Futhermore, three
compounds 1, 4 and 6 were obtained for the first time from the genus Pinus.
Besides, compounds (2, 3, 5, 8, 9) were also subjected to cytotoxicity effect on
SK-LU-1, MCF-7 and Hep-G2 cell lines, but only compound 9 expressed activities
with IC50 values of 141.22, 127.81 and 166.84 MUM, respectively.
PMID- 28691857
TI - A new secondary metabolite from the fermented mycelia of Streptomyces antibiotic
H41-55.
AB - An actinomycete strain, H41-55 from sea sediment was identified as Streptomyces
antibiotic on the basis of its morphological, physiological and biochemical
characteristics as well as 16S rDNA data. A new secondary metabolite, (2S,3R)-N
[3-(formylamino)-2-hydroxybenzoyl]-l-threonine propyl ester (1), together with
five known compounds was isolated from fermentation product by use of silica gel
and Sephadex LH-20 column chromatography, and preparative RP-C18 HPLC, and
identified by HR-TOF-MS and NMR spectra. The cytotoxicities of these isolates
against three cancer cell lines and their antifungal activities on Candida
albicans were tested. Compounds 1, 3, 5, and 6 displayed moderate cytotoxicity. 5
and 6 showed inhibitory activity on C. albicans.
PMID- 28691858
TI - Structural characterisation of a water-soluble polysaccharide from tissue
cultured Dendrobium huoshanense C.Z. Tang et S.J. Cheng.
AB - A water-soluble polysaccharide TC-DHPA4 with a molecular weight of 8.0 * 105 Da
was isolated from tissue-cultured Dendrobium huoshanense by anion exchange and
gel permeation chromatography. Monosaccharide analysis revealed that the
homogeneous polysaccharide was made up of rhamnose, arabinose, mannose, glucose,
galactose and glucuronic acid with a molar ratio of 1.28:1:1.67:4.71:10.43:1.42.
The sugar residue sequence analysis based on the GC-MS files and NMR spectra
indicated that the backbone of TC-DHPA4 consisted of the repeated units:->6)-beta
Galp-(1->6)-beta-Galp-(1->4)-beta-GlcpA-(1->6)-beta-Glcp-(1->6)-beta-Glcp-(->.
The sugar residue sequences beta-Glcp-(1->)-alpha-Rhap-(1->3)-beta-Galp-(1->,
beta-Glcp-(1->4)-alpha-Rhap-(1->3)-beta-Galp-(1->, beta-Galp-(1->6)-beta-Manp-(1
>3)-beta-Galp-(1->, and alpha-l-Araf-(1->2)-beta-Manp-(1->3)-beta-Galp-(1-> were
identified as the branches attached to the C-3 position of (1->6)-linked
galactose in the backbone.
PMID- 28691859
TI - Preliminary studies of berberine and its semi-synthetic derivatives as a
promising class of multi-target anti-parkinson agents.
AB - Parkinson's disease (PD) is a neurodegenerative disorder bearing motor and
nonmotor symptoms. The treatment today is symptomatical rather than preventive or
curative and this leaves the field open for the search of both novel molecular
targets and drug candidates. Interference with alpha-synuclein fibrillation,
monoamine oxidase (MAO) inhibition, modulation of adenosine receptors and the
inhibition of specific phosphodiesterase (PDE) isoforms are some of the currently
pursued strategies. We synthesised and studied some semi-synthetic berberine
derivatives using a set of in silico tools. We evaluated their drug-likeness and
tested the compounds against a set of target proteins involved in the onset or
progression of PD, with a particular attention to MAO-B. Preliminary in vitro
assay on MAO-B confirmed our in silico predictions.
PMID- 28691860
TI - A new furofuran lignan from Piper terminaliflorum Tseng.
AB - The chemical investigation of whole plants Piper terminaliflorum Tseng led to the
isolation of one new furofuran lignan, 7-methoxyasarinin (1), along with three
known amide alkaloids (2-4) as N-3,5-dimethoxy-4-hydroxycinnamoylpyrrole (2),
dihydropipercide (3) and 1-[(2E,4E,9E)-10-(3,4-Methylenedioxyphenyl)-2,4,9
undecatrienoyl]pyrrolidine (4). Their structures were elucidated by extensive
spectroscopic analyses, including 1D, 2D NMR and HR-ESI-MS, and by comparison
with the literature. Compounds (2-4) were isolated from Piper terminaliflorum
Tseng for the first time. All isolated compounds (1-4) were evaluated for their
cytotoxic activities against five human cancer cell lines (including A-549, SMMC
7721, HL-60, MCF-7 and SW-480).
PMID- 28691861
TI - A virtual reality intervention to improve the understanding and empathy for
people with dementia in informal caregivers: results of a pilot study.
AB - OBJECTIVE: Informal caregivers often experience psychological distress due to the
changing functioning of the person with dementia they care for. Improved
understanding of the person with dementia reduces psychological distress. To
enhance understanding and empathy in caregivers, an innovative technology virtual
reality intervention Through the D'mentia Lens (TDL) was developed to experience
dementia, consisting of a virtual reality simulation movie and e-course. A pilot
study of TDL was conducted. METHODS: A pre-test-post-test design was used.
Informal caregivers filled out questionnaires assessing person-centeredness,
empathy, perceived pressure from informal care, perceived competence and quality
of the relationship. At post-test, additional questions about TDL's feasibility
were asked. RESULTS: Thirty-five caregivers completed the pre-test and post-test.
Most participants were satisfied with TDL and stated that TDL gave more insight
in the perception of the person with dementia. The simulation movie was graded
8.03 out of 10 and the e-course 7.66. Participants significantly improved in
empathy, confidence in caring for the person with dementia, and positive
interactions with the person with dementia. CONCLUSION: TDL is feasible for
informal caregivers and seems to lead to understanding of and insight in the
experience of people with dementia. Therefore, TDL could support informal
caregivers in their caregiving role.
PMID- 28691862
TI - Simplifying Breast Imaging Reporting and Data System classification of mammograms
with pure suspicious calcifications.
AB - Objectives To investigate the risk of malignancy following stereotactic breast
biopsy of calcifications classified as Breast Imaging Reporting and Data System
(BI-RADS) 3, 4, and 5. Methods The study included women with pure calcifications
(not associated with masses or architectural distortions) who underwent
stereotactic breast biopsy at the Dutch Cancer Institute between January 2011 and
October 2013. Suspicious calcifications (Breast Imaging Reporting and Data System
3, 4, or 5) detected on mammography were biopsied. All lesions were assessed by
breast radiologists and classified according to the BI-RADS lexicon. Results
Overall, 473 patients underwent 497 stereotactic breast biopsies. Sixty-six
percent (326/497) of calcifications were classified B4, 30% (148/497) B3, and 4%
(23/497) B5. Of the 226 (45%) malignant lesions, there were 182 pure ductal
carcinoma in situ, 22 mixed ductal carcinoma in situ and invasive carcinomas
(ductal or lobular), 21 pure invasive carcinomas, and one angiosarcoma.
Malignancy was found in 32% (95% confidence interval [CI] 0.24 to 0.39) of B3,
49% (95% CI 0.43 to 0.54) of B4, and 83% (95% CI 0.61 to 0.95) of B5
calcifications. Conclusions Considering the high predictive value for malignancy
in B3 calcifications, we propose that these lesions should be classified as
suspicious (B4), especially in a screening setting.
PMID- 28691863
TI - How can those engaging in chemsex best be supported? An online survey to gain
intelligence in Greater Manchester.
AB - Reports of sexualised drug taking (chemsex) have increased significantly in
recent years. There is currently limited intelligence on chemsex outside of
London. An anonymous survey was promoted via several sources including voluntary
services and a sexual health clinic in order to establish the risks associated
with chemsex, and how support services can best be tailored to meet the needs of
those in Greater Manchester, UK. Quantitative and qualitative data were collected
on demographics, drug use, sexual practices and barriers and facilitators to
accessing support. Fifty-two men who have sex with men completed the online
survey. Thirty-nine (75%) were HIV-positive and 11 (21%) were hepatitis C virus
(HCV) positive, all of whom were HIV/HCV co-infected. The most commonly used
drugs were mephedrone (81%) and gamma hydroxybutyrate/gamma butyrolactone (79%).
Nineteen (37%) reported ever injecting drugs. High-risk sexual practices were
reported by respondents. Barriers to accessing support included a fear of being
recognised. Findings demonstrate those engaging in chemsex are participating in a
number of high-risk sexual practices, taking substances with significant risks
and administering these substances in potentially high-risk ways. Results
demonstrate the need for promotion of existing services, with key areas to target
where chemsex sessions are most commonly arranged. Results may be useful in other
metropolitan cities, both for commissioning and tailoring of chemsex support
services.
PMID- 28691864
TI - Outcomes following telestroke-assisted thrombolysis for stroke in Ontario,
Canada.
AB - Introduction Since 2002, the Ontario Telestroke Program has provided hospitals in
under-served regions of the province the opportunity to offer intravenous
thrombolysis with tissue plasminogen activator (IV tPA) to eligible patients. The
purpose of this study was to determine whether telestroke-assisted IV tPA
patients had similar risks of 7- and 90-day mortality, symptomatic intracerebral
haemorrhage (sICH), and poor functional outcome compared to patients who received
IV tPA with on-site expertise. Methods Data from two audits of patients with
acute ischaemic stroke hospitalized in Ontario, Canada in 2010 and 2012 were
analysed. We modelled the risk of all-cause death within 7 and 90 days of
receiving IV tPA using proportional hazards adjusting for hospital type, patient
characteristics, and whether IV tPA was administered as part of a telestroke
consultation. Outcomes of sICH and modified Rankin Scale >= 3 at discharge were
modelled using generalized estimating equations adjusting for the same variables
used in the mortality model. Results There was no difference in 7- or 90-day
mortality among those who received IV tPA with telestroke ( n = 214) compared to
those without ( n = 1885) (7-day adjusted hazard ratio (aHR) 1.29 (95% confidence
interval (CI) 0.68, 2.44); 90-day aHR 1.01 (95% CI 0.67, 1.50)). Complications
were similar between groups, with an adjusted odds ratio (aOR) for sICH of 0.71
(95% CI 0.29, 1.71) and an aOR of 0.75 (95% CI 0.46, 1.23) for poor functional
ability at discharge. Discussion Patients receiving IV tPA supported by
telestroke had similar outcomes to those managed with on-site expertise.
PMID- 28691865
TI - Postpartum Emergency Department Visits and Inpatient Readmissions in a Medicaid
Population of Mothers.
AB - BACKGROUND: Little comprehensive literature exists to broadly examine risk
factors for emergency department (ED) utilization or inpatient admission after
obstetrical delivery. MATERIALS AND METHODS: We conducted a retrospective cohort
study of Medicaid-insured women from 2009 to 2012 who delivered at a regional
perinatal center in the Mid-Atlantic. Women were included if Medicaid was the
primary payer of record for the delivery and there was continuous 9-month
predelivery Medicaid eligibility. Electronic obstetrical data were linked to
Medicaid claims for 9-month prenatal and 6-month postpartum care following
delivery. Negative binomial regression was used to examine factors associated
with an ED visit; multivariable logistic regression was used to examine factors
associated with hospital admission. RESULTS: Following 4484 births, 1564 (34.9%)
mothers had an ED visit, and 298 (6.6%) a hospital admission, within 6 months of
delivery. Mother's race was significantly associated with both ED visits and
inpatient admissions, whereas age and marital status were associated with ED use.
Medical comorbidities, tobacco and substance use, cesarean delivery, and severe
obstetrical morbidity were associated with both ED visits and hospital admission.
In addition, both prenatal opioid use and bipolar disorder increased the odds of
ED use and hospital admission. CONCLUSIONS: Medical, social, and behavioral
characteristics of women, as well as cesarean delivery, were associated with
increased medical utilization in the postpartum.
PMID- 28691866
TI - Safety and pharmacodynamics of venetoclax (ABT-199) in a randomized single and
multiple ascending dose study in women with systemic lupus erythematosus.
AB - Objective The anti-apoptotic protein B-cell lymphoma 2 (Bcl-2) may contribute to
the pathogenesis of systemic lupus erythematosus. The safety, tolerability, and
pharmacodynamics of the selective Bcl-2 inhibitor venetoclax (ABT-199) were
assessed in women with systemic lupus erythematosus. Methods A phase 1, double
blind, randomized, placebo controlled study evaluated single ascending doses (10,
30, 90, 180, 300, and 500 mg) and multiple ascending doses (2 cycles; 30, 60,
120, 240, 400, and 600 mg for 1 week, and then 3 weeks off per cycle) of orally
administered venetoclax. Eligible participants were aged 18-65 years with a
diagnosis of systemic lupus erythematosus for 6 months or more receiving stable
therapy for systemic lupus erythematosus (which could have included
corticosteroids and/or stable antimalarials). Results All patients (48/48)
completed the single ascending dose, 25 continued into the multiple ascending
dose, and 44/50 completed the multiple ascending dose; two of the withdrawals
(venetoclax 60 mg and 600 mg cohorts) were due to adverse events. Adverse event
incidences were slightly higher in the venetoclax groups compared with the
placebo groups, with no dose dependence. There were no serious adverse events
with venetoclax. The most common adverse events were headache, nausea, and
fatigue. Venetoclax 600 mg multiple ascending dose treatment depleted total
lymphocytes and B cells by approximately 50% and 80%, respectively. Naive,
switched memory, and memory B-cell subsets enriched in autoreactive B cells
exhibited dose-dependent reduction of up to approximately 80%. There were no
consistent or marked changes in neutrophils, natural killer cells, hemoglobin, or
platelets. Conclusions Venetoclax was generally well tolerated in women with
systemic lupus erythematosus and reduced total lymphocytes and disease-relevant
subsets of antigen-experienced B cells. Registration ClinicalTrials.gov:
NCT01686555.
PMID- 28691867
TI - An International Survey of Veterinary Students to Assess Their Use of Online
Learning Resources.
AB - Today's veterinary students have access to a wide range of online resources that
support self-directed learning. To develop a benchmark of current global student
practice in e-learning, this study measured self-reported access to, and use of,
these resources by students internationally. An online survey was designed and
promoted via veterinary student mailing lists and international organizations,
resulting in 1,070 responses. Analysis of survey data indicated that students now
use online resources in a wide range of ways to support their learning. Students
reported that access to online veterinary learning resources was now integral to
their studies. Almost all students reported using open educational resources
(OERs). Ownership of smartphones was widespread, and the majority of respondents
agreed that the use of mobile devices, or m-learning, was essential. Social media
were highlighted as important for collaborating with peers and sharing knowledge.
Constraints to e-learning principally related to poor or absent Internet access
and limited institutional provision of computer facilities. There was significant
geographical variation, with students from less developed countries disadvantaged
by limited access to technology and networks. In conclusion, the survey provides
an international benchmark on the range and diversity in terms of access to, and
use of, online learning resources by veterinary students globally. It also
highlights the inequalities of access among students in different parts of the
world.
PMID- 28691868
TI - ClpXP-Dependent RpoS Degradation Enables Full Activation of Type III Secretion
System, Amylovoran Production, and Motility in Erwinia amylovora.
AB - Erwinia amylovora, the causal agent of fire blight disease of apple and pear,
employs intracellular proteases, including Lon and ClpXP, for posttranslational
regulation of various cellular proteins. It has been shown that Lon plays a
critical role in E. amylovora virulence by directly targeting type III secretion
system (T3SS) proteins and the Rcs phosphorelay system. In this study, we
genetically examined the role of ClpXP and its potential interaction with Lon in
E. amylovora. Mutation in clpXP diminished the expression of the T3SS, reduced
exopolysaccharide amylovoran production and motility, and resulted in delayed
disease progress. Western blot analyses showed highly accumulated RpoS proteins
in the clpXP mutant. Moreover, mutation of rpoS in the clpXP mutant background
rescued the expression of the T3SS and amylovoran production, suggesting that
ClpXP-dependent RpoS degradation positively affects virulence traits.
Interestingly, lack of both ClpXP and Lon resulted in significantly reduced
virulence but increased expression of the T3SS and amylovoran production.
However, this phenomenon was independent of RpoS accumulation, suggesting that
ClpXP and Lon are indispensable for full virulence in E. amylovora.
PMID- 28691869
TI - Composite electrospun nanofibers of reduced graphene oxide grafted with poly(3
dodecylthiophene) and poly(3-thiophene ethanol) and blended with
polycaprolactone.
AB - In this paper, an effective method was employed for preparation of nanofibers
using conducting polymer-functionalized reduced graphene oxide (rGO). First,
graphene oxide (GO) was obtained from graphite by Hommer method. GO was reduced
to rGO by NaBH4 and covalently functionalized with a 3-thiophene acetic acid
(TAA) by an esterification reaction to reach 3-thiophene acetic acid
functionalized reduced graphene oxide macromonomer (rGO-f-TAAM). Afterward, rGO-f
TAAM was copolymerized with 3-dodecylthiophene (3DDT) and 3-thiophene ethanol
(3TEt) to yield rGO-f-TAA-co-PDDT (rGO-g-PDDT) and rGO-f-TAA-co-P3TEt (rGO-g
PTEt), which were confirmed by Fourier transform infrared spectra. The grafted
materials depicted better electrochemical properties and superior solubilities in
organic solvents compared to GO and rGO. The soluble rGO-g-PDDT and rGO-g-PTEt
composites blended with polycaprolactone were fabricated by electrospinning, and
then cytotoxicity, hydrophilicity, biodegradability and mechanical properties
were investigated. The grafted rGO composites exhibited a good electroactivity
behavior, mainly because of the enhanced electrochemical performance. The
electrospun nanofibers underwent degradation about 7 wt% after 40 days, and the
fabricated scaffolds were not able to induce cytotoxicity in mouse osteoblast
MC3T3-E1 cells. The soluble conducting composites developed in this study are
utilizable in the fabrication of nanofibers with tissue engineering application.
PMID- 28691870
TI - Recurrence after successful catheter ablation for ventricular arrhythmia from the
aortic root.
AB - OBJECTIVE: The mechanism underlying recurrence after successful ablation of
ventricular arrhythmias (VAs) was unclear. Spectrum analysis can help to identify
near-field activation. The purpose of this study was to quantify the changes of
near-field activation in response to ablation at the VAs origin in the aortic
root (AR-VAs) and to assess its relationship with late ablation outcome. METHODS
AND RESULTS: Patients who underwent acutely successful ablation for AR-VAs were
analysed. Ventricular electrograms acquired before and after ablation at VAs
origin were subjected to spectrum analysis. The area under the curve of the high
frequency component (HFC, 50-200 Hz) and the low frequency component (LFC, 0-50
Hz) was measured. The proportion of HFC to the frequency spectrum of 0-200 Hz was
defined as the HFC ratio (HFCR). The reduction of HFC and HFCR in response to
ablation was defined as HFC pre-post and HFCR pre-post, respectively.
Documentation of VAs with the same morphology after an acute successful procedure
was defined as recurrence. Fifty-six patients were analysed, and VAs recurred in
17 patients. HFCR pre-post, HFC pre-post, and HFC pre-ablation were significantly
higher in patients without recurrence. And HFCR pre-post has the highest
predictive value (area under the receiver-operating characteristic curve: 0.975).
A HFCR pre-post of 1.0% differentiated two groups (sensitivity = 84.6%,
specificity = 100%). Higher HFCR pre-post was correlated with shorter VAs
termination time (correlation coefficient = -0.399, p = .009). CONCLUSIONS: HFCR
pre-post can quantify the near-field activation change during ablation.
Incomplete destruction to the VAs foci could underlie recurrence after successful
ablation.
PMID- 28691871
TI - Non-health care facility medication errors resulting in serious medical outcomes.
AB - OBJECTIVE: The objective of this study is to provide an epidemiologic analysis of
medication errors occurring outside of health care facilities that result in
serious medical outcomes (defined by the National Poison Database System as
"moderate effect," "major effect," "death," or "death, indirect report").
METHODS: National Poison Database System data from 2000 through 2012 were used
for this retrospective analysis of non-health care facility medication errors.
RESULTS: From 2000 through 2012, Poison Control Centers in the United States
received data on 67,603 exposures related to unintentional therapeutic
pharmaceutical errors that occurred outside of health care facilities that
resulted in serious medical outcomes. The overall average rate of these
medication errors was 1.73 per 100,000 population, and there was a 100.0% rate
increase during the 13-year study period. Medication error frequency and rates
increased for all age groups except children younger than 6 years of age. Medical
outcome was most commonly reported as moderate effect (93.5%), followed by major
effect (5.8%) and death (0.6%). Common types of medication errors included
incorrect dose, taking or administering the wrong medication, and inadvertently
taking the medication twice. The medication categories most frequently associated
with serious outcomes were cardiovascular drugs (20.6%) (primarily beta blockers,
calcium antagonists, and clonidine), analgesics (12.0%) (most often opioids and
acetaminophen, alone and combination products), and hormones/hormone antagonists
(11.0%) (in particular, insulin, and sulfonylurea). CONCLUSIONS: This study
analyzed non-health care facility medication errors resulting in serious medical
outcomes. The rate of non-health care facility medication errors resulting in
serious medical outcomes is increasing, and additional efforts are needed to
prevent these errors.
PMID- 28691872
TI - Organic contamination in clams, Venerupis aurea laeta and Cerastoderma edule
glaucum, from Sicily (Italy).
AB - Two species of edible clams Venerupis aurea laeta and Cerastoderma edule glaucum
from Ganzirri Lake (Sicily, Italy) were investigated to determine OCP and PCB
residues by GC-MS. Thirty-five samples were examined for two years in order to
perform: a) their actual contamination; b) the daily dietary exposure of seafood
consumers to the pollutants in question. In all the clams analysed in this study,
PCB and OCP (4,4'-DDE) residues are always below the limits fixed by law. It
seems that there is some seasonality of concentrations observed. In fact the more
high concentrations of residues are detected in the hot months, for both species
and years. Given the consumption of clams and the values obtained in this study
for the two species analysed, it is possible estimate that the average daily
dietary intake of NDL-PCB and of 4,4'-DDE for adults is really low.
PMID- 28691873
TI - Immune-inflammatory activation after a single laparotomy in a rat model: effect
of adenosine, lidocaine and Mg2+ infusion to dampen the stress response.
AB - Our aim was to examine the effect of low-volume 0.9% NaCl adenosine, lidocaine
and Mg2+ (ALM) 'drip' on early immune-inflammatory activation after a single
laparotomy with no further manipulation. Male Sprague-Dawley rats were
anesthetized and randomly assigned to one of the groups, baseline, 1 h infusion
0.9% NaCl +/- ALM and metrics, 1 h infusion and 6-h metrics, and 6 h continuous
infusion and metrics. Complete blood count, acid-base balance, systemic levels of
IL-6 and IL-10, and coagulation status were measured. After 1 h, there was a
disproportionate increase in circulating neutrophils between saline and ALM
groups despite an identical 45% fall in lymphocytes. Disproportionate increases
also occurred in platelet counts 1 h after surgery, and saline controls had
increased respiratory alkalosis at 6 h with higher lactate. Systemic inflammation
was also evident after 1 h in both groups (plasma IL-6 increase) and was
amplified in saline-controls after 6 h. The ALM group increased anti-inflammatory
cytokine IL-10. Surgery was not associated with acute coagulopathy; however,
there were significant reductions in fibrinolysis. Following a single laparotomy,
ALM infusion appeared to reduce stress-induced release of neutrophils and
platelets into the circulation, and reduced acid-base disturbance. After 1 h,
both groups had similar IL-6 levels, but ALM animals had increased IL-10,
indicating improved inflammatory balance. The uncoupling of inflammation and
coagulation activation but not fibrinolysis may offer a unique opportunity to
investigate differential activation of innate immunity in response to sterile
injury in this model.
PMID- 28691874
TI - New beta-orcinol depsides from Hypotrachyna caraccensis, a lichen from the paramo
ecosystem and their free radical scavenging activity.
AB - The new hypotrachynin A (1) and B (2) along with the known (+)-(9b-R)-usnic (3)
and methylstictic acids (4) were isolated for the first time from Hypotrachyna
caraccensis. Additionally, their potency and reactivity as DPPH* scavengers was
determined by a kinetic study calculating their EC50 and second-order rate
constants (k2). Considering 1-4 could be dermatological agents, their n-octanol
water partition coefficients and standard molar Gibbs free energies of transfer
were calculated as estimation of their lipophilicity and skin penetration.
Compounds 1, 3 and 4 were less potent than 2 (EC50 = 3.3014; 1.7540; 2.6652 vs
0.7376) as DPPH* scavengers, in turn 4, was the most reactive with a comparable
k2 to the antioxidant BHT (k2 = (232 +/- 24) * 10-2 vs (564 +/- 12) * 10-2 M-1 s
1, respectively). Since 2 and 4 had an optimal lipophilicity and permeability for
skin penetration, they might be developed as topical ingredients to prevent
oxidative damage.
PMID- 28691875
TI - Steve Zarit's Swansong.
PMID- 28691876
TI - [Physiological, pathophysiological and clinical significance of
chromogranins/secretogranins].
AB - This paper investigates the fundamental knowledge, build-up, as well as essential
structural and important features of the big family of
chromogranins/secretogranins. Previously the different properties and the
slightly diverging funcional relations of the two family members were in focus.
Later on, it has been discovered that they are essentially two similar compounds
with identical structures and functions, and they are chemically, biochemically
related. From details discovered so far we can tell that they are long polypeptid
chains formed from amino acids. Based on insights gained until now we can also
state that these compounds are formed in Ca++ containing environments with acidic
pH. Among the compounds there are several molecules which have characteristic
oligosacharid groups. This is especially interesting because oligosacharid chains
with sialic acid in terminal position play an important role in the recognising
and connectional processes. The chromogranins/secretogranins are mostly formed in
neuroendocrine cells, but are also capable of building up in any cell type in the
organism during pathological processes. Intracellular biogenesis takes place in
the dense endoplasmatic reticulum across the mitochondrium, developing biogenetic
granulums, followed by the stimulus-motivated secretum (exocytosis). The next
stage of the molecular development is the specific break-up of the long
polypeptid chains into shorter fragments. These fragments have individual
effects. Some important clinical (diagnostic, prognostic) significance and
connections are also touched upon in this paper, however, the cardiovascular,
immunological systems and the tumors are mostly in focus. There are more
immunological, cardiovascular and tumoral data. It is stated that as these
molecules are in close connection with all of the organisms and systems of the
body, a new chief organisator system has been identified. This chief organisator
is closely connected with the central nervous system. Orv Hetil. 2017; 158(28):
1092-1099.
PMID- 28691877
TI - [Miscellaneous].
PMID- 28691878
TI - [Molecular background of the melanoma and the brain metastasis].
AB - Malignant melanoma is one of the most aggressive tumors which often gives
metastasis to distant organs thereby limiting the chances of survival. Brain
metastasis occurs in nearly half of the advanced tumors. In order to improve
outcome early diagnosis is important. The discovery and better understanding of
genetic and epigenetic changes is essential for developing new effective
therapies, which can designate promising therapeutic targets. Melanoma most often
is caused by gene mutations of the mitogen-activated protein kinase pathway, the
phosphatidylinositol 3-kinase signaling pathway, and the cell cycle regulatory
molecules, respectively. The molecular process of brain metastasis has not been
fully elucidated. In our review we summarize the genetic alterations and
molecular mechanisms playing a role in the development of melanoma and its brain
metastasis. Orv Hetil. 2017; 158(28): 1083-1091.
PMID- 28691879
TI - [Resection of liver and abdominal wall metastasis 11 years after
pancreatoduodenectomy. Case report].
AB - Pancreatic cancer has adverse prognosis. Disease recurrence is typical and it
occurs mainly within the first 2 years postoperatively. However late and soliter
metastases are rare. This case report shows the history of a male patient, who
was radically operated on for pancreatic cancer. 11 years later a solitary liver
metastasis has developed and it was completely removed by resection. 1 year
postoperatively the patient is doing well. Our case demonstrates that in patients
after resection for pancreatic cancer, redo surgery might be justified in case of
late and isolated metastasis. Orv Hetil. 2017; 158(28): 1109-1111.
PMID- 28691880
TI - [Five-year experience with the multidisciplinary evaluation of breast lesions
according to the Decker radio-pathologic correlation system].
AB - INTRODUCTION: Lesions identified during breast imaging often require microscopic
verification. Current recommendations imply the classification of radiological,
clinical, cytology and core biopsy findings into one of five predefined
categories. The Decker system also includes a classification of both the
correlation between radiology and pathology and the actions required on this
basis. AIM: To report on the five-year results of the implementation of the
Decker system in our pretreatment multidisciplinary breast team. METHOD:
Retrospective analysis of patients operated on because of breast diseases or
appearing at the multidisciplinary breast team during the period between 2000 and
2014. RESULTS: Of 1716 cases discussed, 1531 were solved by non-operative
diagnostics, 157 required diagnostic excisions; 1122 cases (65%) proved to be
malignant. Malignancy was diagnosed by core needle biopsies in 69% of the cases.
The non-operative approach was unsuccessful, delayed or wrong in 14 cases.
CONCLUSION: Breast lesions need to be evaluated in a multidisciplinary setting.
The Decker-system is suitable for the recording and analysis of the correlation
between radiologic/physical and microscopy findings, and of the ensuing
diagnostic/therapeutic actions. Orv Hetil. 2017; 158(28): 1100-1108.
PMID- 28691881
TI - [Lajos Markusovszky Memorial Meeting - 2017].
PMID- 28691882
TI - [In memoriam Lilly Dubowitz (March 20, 1930-March 14, 2016)].
PMID- 28691883
TI - Correction to: Bahabadi M, et al., Hepatoprotective effect of parthenolide in rat
model of nonalcoholic fatty liver disease.
PMID- 28691884
TI - Synergistic Antimicrobial Combinations Inhibit and Inactivate Listeria
monocytogenes in Neutral and Acidic Broth Systems.
AB - The use of antimicrobial compounds can be an effective approach to control
Listeria monocytogenes in ready-to-eat foods, but it can also be limited by cost,
restrictions on concentrations in foods, and potential changes to organoleptic
properties. Combinatorial approaches that produce additive or synergistic effects
allow for reductions in individual antimicrobial concentrations while achieving
the same level of control. The present study determined the MIC and MBC of an
antimicrobial compound when used alone or in binary combinations against L.
monocytogenes in growth media adjusted to pH values 7.4 and 5.5 and characterized
interactions as synergistic, additive, or antagonistic. Inhibitory and
bactericidal concentrations were defined as changes in L. monocytogenes counts of
<=1.0 or >=3.0 log CFU/mL compared with the starting inoculum, respectively.
Individually, lauric arginate (LAE), hydrogen peroxide (HP), and epsilon
polylysine (EPL) inhibited L. monocytogenes growth at the lowest concentrations
when applied alone in broth adjusted to pH 7.4. Similarly, LAE, EPL, and HP had
the lowest MBCs in broth adjusted to both pH levels. The inhibitory efficacy of
both caprylic acid and sodium caprylate (SC) increased at the lower pH, with
reductions in MICs of >98%. In total, 35 and 19 additive or synergistic
inhibitory and bactericidal combinations were identified at pH values 7.4 and
5.5, respectively. Combinations of acidified calcium sulfate with lactic acid
(ACSL) and SC were among the most synergistic inhibitory groupings at both pH
levels, whereas EPL+LAE were the most effective bactericides at pH 7.4.
Combinations of SC with EPL or ACSL were also among the most effective
bactericides at pH 5.5. These data serve as a foundation for developing more
effective antimicrobial approaches for the control of L. monocytogenes in foods
with different pH levels.
PMID- 28691885
TI - Targeting of Antithrombin in Hemophilia A or B with RNAi Therapy.
AB - BACKGROUND: Current hemophilia treatment involves frequent intravenous infusions
of clotting factors, which is associated with variable hemostatic protection, a
high treatment burden, and a risk of the development of inhibitory
alloantibodies. Fitusiran, an investigational RNA interference (RNAi) therapy
that targets antithrombin (encoded by SERPINC1), is in development to address
these and other limitations. METHODS: In this phase 1 dose-escalation study, we
enrolled 4 healthy volunteers and 25 participants with moderate or severe
hemophilia A or B who did not have inhibitory alloantibodies. Healthy volunteers
received a single subcutaneous injection of fitusiran (at a dose of 0.03 mg per
kilogram of body weight) or placebo. The participants with hemophilia received
three injections of fitusiran administered either once weekly (at a dose of
0.015, 0.045, or 0.075 mg per kilogram) or once monthly (at a dose of 0.225,
0.45, 0.9, or 1.8 mg per kilogram or a fixed dose of 80 mg). The study objectives
were to assess the pharmacokinetic and pharmacodynamic characteristics and safety
of fitusiran. RESULTS: No thromboembolic events were observed during the study.
The most common adverse events were mild injection-site reactions. Plasma levels
of fitusiran increased in a dose-dependent manner and showed no accumulation with
repeated administration. The monthly regimen induced a dose-dependent mean
maximum antithrombin reduction of 70 to 89% from baseline. A reduction in the
antithrombin level of more than 75% from baseline resulted in median peak
thrombin values at the lower end of the range observed in healthy participants.
CONCLUSIONS: Once-monthly subcutaneous administration of fitusiran resulted in
dose-dependent lowering of the antithrombin level and increased thrombin
generation in participants with hemophilia A or B who did not have inhibitory
alloantibodies. (Funded by Alnylam Pharmaceuticals; ClinicalTrials.gov number,
NCT02035605 .).
PMID- 28691886
TI - Salivary Levels of NLRP3 Inflammasome-Related Proteins as Potential Biomarkers of
Periodontal Clinical Status.
AB - BACKGROUND: Emerging evidence suggests that activation of inflammasomes plays a
central mechanism in pathogenesis of periodontitis. This study aims to compare
salivary levels of nod-like receptor family pyrin domain containing protein
(NLRP) 3, apoptosis-associated speck-like protein containing a caspase
recruitment domain (ASC), cysteine aspartase (caspase)-1, and interleukin (IL)
1beta from individuals with aggressive (AgP) or chronic periodontitis (CP) and
healthy controls (HC), as well as elucidate its association with periodontal
clinical status. METHODS: Saliva samples from individuals with CP (n = 75), AgP
(n = 20), and HC (n = 69) were collected. Periodontal status was assessed by
measurement of probing depth, clinical attachment level, and extent and severity
of disease. Salivary levels of analytes were analyzed by enzyme-linked
immunosorbent assay. Association between biomarkers with CP or AgP was analyzed
using multivariate binary logistic regression models. RESULTS: Significantly
higher levels of NLRP3, ASC, and IL-1beta were detected in periodontitis groups
in comparison to the periodontally HC group. However, no significant differences
were observed for caspase-1 levels between clinical groups, and only NLRP3
salivary concentration was significantly higher in AgP compared with CP patients.
Also, positive significant correlations among NLRP3, ASC, and IL-1beta salivary
concentrations and clinical parameters were observed. Logistic regression
analyses revealed a strong/independent association of NLRP3, ASC, and IL-1beta
salivary levels with CP and AgP. CONCLUSION: Although the concentration of
caspase-1 in saliva samples makes its determination useless for detection of
periodontal disease and/or its severity, salivary levels of NLRP3, ASC, and IL
1beta may act as strong/independent indicators of amount and extent of
periodontal breakdown in both CP and AgP and could potentially be used for
prevention and therapy of this group of diseases.
PMID- 28691887
TI - Effects of an Erbium:Yttrium-Aluminum-Garnet Laser and Ultrasonic Scaler on
Titanium Dioxide-Coated Titanium Surfaces Contaminated With Subgingival Plaque:
An In Vitro Study to Assess Post-Treatment Biocompatibility With Osteogenic
Cells.
AB - BACKGROUND: Effects of conventional ultrasonic scaler versus an erbium:yttrium
aluminum-garnet (Er:YAG) laser on titanium surfaces contaminated with subgingival
plaque from patients with peri-implantitis are evaluated in terms of: 1) plaque
and biocorroded titanium oxide coating removal; 2) surface change induction; and
3) residual biocompatibility toward osteoblasts. METHODS: Subgingival plaque
coated titanium disks with a moderately rough surface were fixed with ethanol and
treated with an ultrasonic scaler (metal tip) or Er:YAG laser (20.3 or 38.2
J/cm2) in non-contact mode. Fluorescent detection of residual plaque was
performed. Disk surface morphology was evaluated by scanning electron microscopy.
Viability, attachment, proliferation, and differentiation of Saos-2 osteoblasts
on new and treated disks were assayed by propidium iodide/DNA stain assay and
confocal microscopic analysis of cytoskeleton, Ki67, expression of osteopontin
and alkaline phosphatase, and formation of mineralized nodules. RESULTS: Both
methods resulted in effective debridement of treated surfaces, the plaque area
being reduced to 11.7% with the ultrasonic scaler and <=0.03% with the Er:YAG
laser (38.2 J/cm2). Ultrasound-treated disks showed marked surface changes,
incomplete removal of the titanium dioxide (TiO2) layer, and scanty plaque
aggregates, whereas the Er:YAG laser (38.2 J/cm2) completely stripped away the
plaque and TiO2 layer, leaving a micropitted surface. Both treatments maintained
a good biocompatibility of surfaces to Saos-2 osteoblasts. Air-water cooling kept
disk temperature below the critical threshold of 47 degrees C. CONCLUSION: This
study shows that an ultrasonic scaler with metal tip is less efficient than high
energy Er:YAG irradiation to remove the plaque and TiO2 layer on anodized disks,
although both procedures appear capable of restoring an adequate
osseoconductivity of treated surfaces.
PMID- 28691888
TI - Signal-Regulated Protein Kinases/Protein Kinase B-p53-BH3-Interacting Domain
Death Agonist Pathway Regulates Gingipain-Induced Apoptosis in Osteoblasts.
AB - BACKGROUND: Gingipains are cysteine proteases produced by Porphyromonas
gingivalis, the predominant pathogen in chronic periodontitis. The present study
aims to examine the role of gingipains in promoting apoptosis in osteoblasts.
METHODS: Human calvarial osteoblasts and osteoblast MC3T3-E1 cells were treated
with 8.348 U/L gingipains. Flow cytometry analysis and terminal deoxynucleotidyl
transferase-mediated deoxy-UTP nick end labeling staining were used to detect
cell apoptosis. Protein expression was examined by Western blotting, and gene
expression was detected by real-time polymerase chain reaction. Small interfering
(si)RNA transfection was used to knock down BH3-interacting domain death agonist
(Bid) expression. RESULTS: Treatment with 8.348 U/L gingipains from 4 to 72 hours
increased apoptosis, accompanied by elevated cleaved caspase-3 levels. Notably,
gingipain-induced apoptosis was associated with increase of Bid and its truncated
form, tBid, as well as p53. Transfection with Bid siRNA resulted in suppression
of gingipain-induced apoptosis. The p53 inhibitor, Pifithrin-alpha, blocked the
gingipain-induced Bid. The ability of gingipains to stimulate p53 and Bid
expression was mimicked by PD-0325901 and MK-2206, the specific extracellular
signal-regulated protein kinases (ERK) and protein kinase B (PKB) inhibitors,
respectively. Furthermore, treatment with gingipains reduced phospho-ERK and
phospho-PKB levels, an effect correlated to gingipain-induced increase in p53 and
tBid expression. CONCLUSION: The present findings suggest that Bid plays an
essential role in gingipain-induced osteoblast apoptosis, which is dependent on
inhibition of ERK and PKB phosphorylation, followed by the activation of p53.
PMID- 28691889
TI - Osborn wave mimicking Brugada sign.
PMID- 28691890
TI - MTRR rs1801394 and its interaction with MTHFR rs1801133 in colorectal cancer: a
case-control study and meta-analysis.
AB - AIM: This study aims to evaluate the association between the MTRR rs1801394 alone
or in interaction with the MTHFR rs1801133 and susceptibility to colorectal
cancer (CRC) and its characteristics in Iranian population. Additionally, both a
systematic review and meta-analysis were performed to derive a more precise
assessment of this association. MATERIALS & METHODS: Genomic DNA of 2332 subjects
was genotyped for rs1801394. These data were pooled with 17 eligible studies for
meta-analysis. RESULTS: No significant association was found between the
rs1801394 or rs1801394-rs1801133 and CRC risk. Meta-analysis results also
demonstrated no significant relationship between the rs1801394 and CRC risk.
CONCLUSION: Results of this study showed that the rs1801394 alone or together
with the rs1801133 is not a risk factor for CRC in Iranian population.
PMID- 28691891
TI - Incidence of OXA-23 and OXA-58 Carbapenemases Coexpressed in Clinical Isolates of
Acinetobacter baumannii in Tunisia.
AB - Acinetobacter baumannii is an important opportunistic and multidrug-resistant
pathogen responsible for nosocomial infections in health facilities. The aim of
this study was to characterize the molecular mechanisms of carbapenem resistance
in A. baumannii isolates isolated from Mohamed Kassab Orthopedic Institute in
Tunis, Tunisia. Twenty-five imipenem-resistant A. baumannii clinical isolates
collected between 2013 and 2016 were identified using API 20NE and were confirmed
by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry
(MALDI-TOF/MS). Carbapenemase activity was detected using microbiological tests
and PCR. The epidemiological relatedness of the isolates was studied using
multilocus sequence typing (MLST). The isolates were resistant to all antibiotics
tested with increased minimum inhibitory concentration values (>32 mg/L). The
microbiological tests showed that the 25 A. baumannii were positive for modified
Hodge test and for the Carba NP test; however, beta-lactamase activity was not
inhibited by EDTA. All the isolates harbored the naturally occurring blaOXA-51
like gene and the blaOXA-23-like carbapenemase gene. Among these isolates, one
isolate coexpressed the blaOXA-58 gene. MLST revealed several sequence types
(STs) with the predominance of ST2 imipenem-resistant A. baumannii (14/25; 56%).
In this study we report the prevalence of ST2 imipenem resistance and for the
first time the coexpression of blaOXA-23 and blaOXA-58 in clinical isolates of A.
baumannii in a Tunisian hospital.
PMID- 28691892
TI - Paclitaxel induces autophagy in gastric cancer BGC823 cells.
AB - This paper explores the connection between paclitaxel, a chemotherapeutic agent,
and gastric cancer cells. In this experiment, it is demonstrated that paclitaxel
triggers autophagy and inhibits proliferation of gastric cancer cells. An 3-(4,5
dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay was used
to detect cell viability and the IC50 of paclitaxel. Western blot was used to
detect the expression levels of P62, and to measure the protein expression of
autophagy. Immunofluorescence was used to reveal the appearance of punctate
structures in the cytoplasm-this ultrastructure associated with autophagy was
observed by microscopy. Electron microscopy revealed the formation of double
membrane autophagosomes, a typical structure of autophagy. In conclusion, our
research indicates that paclitaxel may influence gastric cancer BGC823 cells by
way of inducing autophagy.
PMID- 28691893
TI - Sleep and mood changes in advanced age after blue-blocking (yellow) intra ocular
lens (IOLs) implantation during cataract surgical treatment: a randomized
controlled trial.
AB - OBJECTIVES: Both advanced age and depression are characterized by changes in
sleep patterns. Light exposure is one of the main synchronizers of circadian
cycles and influences sleep by inhibiting melatonin secretion, which is mostly
sensitive to light of low wavelengths (blue). Blue-blocking (yellow) intraocular
lenses (IOLs) have supplanted the usual UV-blocking (clear) IOLs during cataract
surgery to prevent age-related macular degeneration, however, the impact of
yellow IOLs on sleep and mood is unclear. The purpose of this study was to
compare the effects of yellow and clear IOLs on sleep and mood in aged patients
undergoing bilateral cataract surgery. METHODS: A randomized controlled
superiority study was conducted within three ophthalmic surgical wards in France.
A total of 204 subjects (mean age 76.2 +/- 7.5 years) were randomized into yellow
or clear IOLs groups. Patients completed a sleep diary, the pictorial sleepiness
scale and the Beck Depression Inventory (BDI) one week before and eight weeks
after the last surgical procedure. RESULTS: According to an Intent To Treat (ITT)
analysis, no significant difference was found between yellow and clear IOLs
groups regarding sleep time, sleep latency, total sleep duration, quality of
sleep and BDI scores. The rate of patients whose BDI score increased at the
cutoff score of >=5 after surgery was significantly higher in the yellow IOL
group (n = 11, 13.1%) compared with the clear IOL group (n = 4; 4.7%); p = 0.02.
CONCLUSIONS: Using yellow IOLs for cataract surgery doesn't significantly impact
sleep but may induce mood changes in aging.
PMID- 28691894
TI - Characterization of PTV-12, a newly described porcine teschovirus serotype: in
vivo infection and cross-protection studies.
AB - Porcine teschoviruses (PTVs) constitute 1 of the 31 genera within the
Picornaviridae family, comprising at least 13 genetic types (PTV-1 to PTV-13), of
which only 11 (PTV-1 to PTV-11) have been recognized as serotypes to date.
Specific for swine and wild boars, most PTVs are usually non-pathogenic, but some
viral variants cause severe disorders in the central nervous system (Teschen
disease) or milder signs (Talfan disease), as well as reproductive, digestive and
respiratory disorders and skin lesions. Previous studies revealed a high
diversity of teschoviruses circulating in Spanish pig populations. Phylogenetic
analysis performed with these sequences and others available in GenBank disclosed
13 clusters, 11 of which corresponded to the known PTV serotypes, and 1 of 2
additional groups is represented by isolate CC25, whose full-length genomic
sequence has been obtained. This group is new to science, and was putatively
named PTV-12. Here, a complete characterization of this isolate is presented,
including the experimental infection of minipigs to assess tissue tropism and
possible pathogenicity in vivo in the host species. In addition, using this
experimental animal model, we investigated whether a pre-existing infection with
this PTV-12 isolate could confer cross-protection against infection with a
heterotypic PTV-1 virulent strain. Based on phylogenetic analysis and serological
data, we propose CC25 as the prototype strain of a new teschovirus serotype, PTV
12.
PMID- 28691895
TI - Low fraction of the 222K PrP variant in the protease-resistant moiety of PrPres
in heterozygous scrapie positive goats.
AB - The presence of lysine (K) at codon 222 has been associated with resistance to
classical scrapie in goats, but few scrapie cases have been identified in 222Q/K
animals. To investigate the contribution of the 222K variant to PrPres formation
in natural and experimental Q/K scrapie cases, we applied an immunoblotting
method based on the use of two different monoclonal antibodies, F99/97.6.1 and
SAF84, chosen for their different affinities to 222K and 222Q PrP variants. Our
finding that PrPres seems to be formed nearly totally by the 222Q variant
provides evidence that the 222K PrP variant confers resistance to conversion to
PrPres formation and reinforces the view that this mutation has a protective role
against classical scrapie in goats.
PMID- 28691896
TI - Assessing the risk of cytomegalovirus DNAaemia in allogeneic stem cell transplant
recipients by monitoring oxidative-stress markers in plasma.
AB - The level of antioxidants, such as thiol-containing tripeptide glutathione (GSH),
in cytomegalovirus (CMV)-infected cells is notably increased. We previously
showed that GSH levels in plasma, as measured by untargeted 1H nuclear magnetic
resonance, are higher in allogeneic stem cell transplant (allo-SCT) recipients
who subsequently develop CMV viraemia. We hypothesized that the net level of
oxidative-stress markers present in plasma may be reduced in patients who develop
CMV DNAaemia compared to those who do not. We serially monitored the levels of
malondialdehyde (MDA) and carbonylated proteins (CPs) early after allo-SCT and
assessed whether they could predict the occurrence of CMV DNAaemia. MDA levels
were measured in 43 patients (28 had CMV DNAaemia) and CPs were quantified in 53
patients (38 patients developed CMV DNAaemia). The area under the curve (AUC)
value for MDA, but not for CPs, was significantly lower in patients who
subsequently developed CMV DNAaemia compared to those who remained DNAaemia-free
(P=0.043). A trend toward lower MDA AUC values was observed in episodes of CMV
DNAaemia with faster CMV replicative kinetics and in those who reached higher
peak CMV DNA levels. Moreover, receiver operating characteristic curve analyses
indicated that the MDA biomarker had the predictive ability to discriminate
between patients with or without subsequent CMV DNAaemia (AUC=0.69, 95 %
confidence interval 0.51-0.85, P=0.05). In summary, serial quantitation of MDA
may be useful for individualizing antiviral prophylaxis therapies (targeted
prophylaxis) in the upcoming era of new antiviral drugs with improved safety
profiles.
PMID- 28691897
TI - Intranasal immunization with inactivated feline calicivirus particles confers
robust protection against homologous virus and suppression against heterologous
virus in cats.
AB - The protective efficacy of intranasal (IN) administration of inactivated feline
calicivirus (FCV) vaccine against homologous or heterologous FCV infection was
investigated. Groups of cats immunized with the experimental inactivated, non
adjuvanted FCV vaccine via either the IN or subcutaneous (SC) route were exposed
to homologous or highly heterologous FCV. Both the IN and SC immunization
protocols established robust protection against homologous FCV infection.
Although neither immunization regimen conferred protection against the
heterologous strain, clinical scores and virus titres of oral swabs were lower in
cats in the IN group compared to those in the SC group, accompanying a faster
neutralizing antibody response against the heterologous virus in cats in the IN
group. The IN group secreted more IgA specific to FCV proteins in oral washes
(lavage fluids from the oral cavity) than the SC group. IN immunization with an
inactivated whole FCV particle, which protects cats from homologous virus
exposure and shortens the period of heterologous virus shedding, may serve as a
better platform for anti-FCV vaccine.
PMID- 28691898
TI - Post-transcriptional regulation of target genes by the sRNA FnrS in Neisseria
gonorrhoeae.
AB - Small non-coding RNAs (sRNAs) are well-established post-transcriptional
regulators of gene expression in bacteria that respond to a variety of
environmental stimuli. They usually act by base-pairing with their target mRNAs,
which is commonly facilitated by the RNA chaperone Hfq. In this study we
initiated the analysis of the sRNA FnrS of Neisseria gonorrhoeae, which is
induced under anaerobic conditions. We identified four putative FnrS target genes
using bioinformatics approaches and validated these target genes using
translational reporter gene fusions in both Escherichia coli and N. gonorrhoeae,
thereby demonstrating their downregulation by direct base-pairing between the
respective mRNA and FnrS. We demonstrate deregulation of target mRNAs upon
deletion of fnrS and provide evidence that the isc gene cluster required for iron
sulfur cluster biosynthesis, which harbours iscS, which is a direct target of
FnrS, is coordinately downregulated by the sRNA. By mutational analysis we show
that, surprisingly, three distinct regions of FnrS are employed for interaction
with different target genes.
PMID- 28691899
TI - Aggregation of a hepatitis C virus replicase module induced by ablation of
p97/VCP.
AB - Hijacking host membranes to assemble a membrane-associated viral replicase is a
hallmark of almost all positive-strand RNA viruses. However, how the virus co
opts host factors to facilitate this energy-unfavourable process is incompletely
understood. In a previous study, using hepatitis C virus (HCV) as a model and
employing affinity purification of the viral replicase, we identified a valosin
containing protein (p97/VCP), a member of the ATPases associated with diverse
cellular activities (AAA+ ATPase family), as a viral replicase-associated host
factor. It is required for viral replication, depending on its ATPase activity.
In this study, we used VCP pharmacological inhibitors and short hairpin (sh) RNA
mediated knockdown to ablate VCP function and then dissected the roles of VCP in
viral replicase assembly in an HCV subgenomic replicon system and a viral
replicase assembly surrogate system. Ablation of VCP specifically resulted in the
pronounced formation of an SDS-resistant aggregation of HCV NS5A and the
reduction of hyperphosphorylation of NS5A. The NS5A dimerization domain was
indispensable for aggregation and the NS5A disordered regions also contributed to
a lesser extent. The reduction of the hyperphosphorylation of NS5A coincided with
the aggregation of NS5A. We propose that HCV may co-opt VCP to disaggregate an
aggregation-prone replicase module to facilitate its replicase assembly.
PMID- 28691900
TI - Ionic mechanisms underlying history-dependence of conduction delay in an
unmyelinated axon.
AB - Axonal conduction velocity can change substantially during ongoing activity, thus
modifying spike interval structures and, potentially, temporal coding. We used a
biophysical model to unmask mechanisms underlying the history-dependence of
conduction. The model replicates activity in the unmyelinated axon of the
crustacean stomatogastric pyloric dilator neuron. At the timescale of a single
burst, conduction delay has a non-monotonic relationship with instantaneous
frequency, which depends on the gating rates of the fast voltage-gated Na+
current. At the slower timescale of minutes, the mean value and variability of
conduction delay increase. These effects are because of hyperpolarization of the
baseline membrane potential by the Na+/K+ pump, balanced by an h-current, both of
which affect the gating of the Na+ current. We explore the mechanisms of history
dependence of conduction delay in axons and develop an empirical equation that
accurately predicts this history-dependence, both in the model and in
experimental measurements.
PMID- 28691901
TI - Decoding temporal interpretation of the morphogen Bicoid in the early Drosophila
embryo.
AB - Morphogen gradients provide essential spatial information during development. Not
only the local concentration but also duration of morphogen exposure is critical
for correct cell fate decisions. Yet, how and when cells temporally integrate
signals from a morphogen remains unclear. Here, we use optogenetic manipulation
to switch off Bicoid-dependent transcription in the early Drosophila embryo with
high temporal resolution, allowing time-specific and reversible manipulation of
morphogen signalling. We find that Bicoid transcriptional activity is dispensable
for embryonic viability in the first hour after fertilization, but persistently
required throughout the rest of the blastoderm stage. Short interruptions of
Bicoid activity alter the most anterior cell fate decisions, while prolonged
inactivation expands patterning defects from anterior to posterior. Such anterior
susceptibility correlates with high reliance of anterior gap gene expression on
Bicoid. Therefore, cell fates exposed to higher Bicoid concentration require
input for longer duration, demonstrating a previously unknown aspect of Bicoid
decoding.
PMID- 28691902
TI - Essential roles of Caspase-3 in facilitating Myc-induced genetic instability and
carcinogenesis.
AB - The mechanism for Myc-induced genetic instability is not well understood. Here we
show that sublethal activation of Caspase-3 plays an essential, facilitative role
in Myc-induced genomic instability and oncogenic transformation. Overexpression
of Myc resulted in increased numbers of chromosome aberrations and gammaH2AX foci
in non-transformed MCF10A human mammary epithelial cells. However, such increases
were almost completely eliminated in isogenic cells with CASP3 gene ablation.
Furthermore, we show that endonuclease G, an apoptotic nuclease downstream of
Caspase-3, is directly responsible for Myc-induced genetic instability. Genetic
ablation of either CASP3 or ENDOG prevented Myc-induced oncogenic transformation
of MCF10A cells. Taken together, we believe that Caspase-3 plays a critical,
unexpected role in mediating Myc-induced genetic instability and transformation
in mammalian cells.
PMID- 28691903
TI - Sequential neuromodulation of Hebbian plasticity offers mechanism for effective
reward-based navigation.
AB - Spike timing-dependent plasticity (STDP) is under neuromodulatory control, which
is correlated with distinct behavioral states. Previously, we reported that
dopamine, a reward signal, broadens the time window for synaptic potentiation and
modulates the outcome of hippocampal STDP even when applied after the plasticity
induction protocol (Brzosko et al., 2015). Here, we demonstrate that sequential
neuromodulation of STDP by acetylcholine and dopamine offers an efficacious model
of reward-based navigation. Specifically, our experimental data in mouse
hippocampal slices show that acetylcholine biases STDP toward synaptic
depression, whilst subsequent application of dopamine converts this depression
into potentiation. Incorporating this bidirectional neuromodulation-enabled
correlational synaptic learning rule into a computational model yields effective
navigation toward changing reward locations, as in natural foraging behavior.
Thus, temporally sequenced neuromodulation of STDP enables associations to be
made between actions and outcomes and also provides a possible mechanism for
aligning the time scales of cellular and behavioral learning.
PMID- 28691904
TI - Synthetic lethality between the cohesin subunits STAG1 and STAG2 in diverse
cancer contexts.
AB - Recent genome analyses have identified recurrent mutations in the cohesin complex
in a wide range of human cancers. Here we demonstrate that the most frequently
mutated subunit of the cohesin complex, STAG2, displays a strong synthetic lethal
interaction with its paralog STAG1. Mechanistically, STAG1 loss abrogates sister
chromatid cohesion in STAG2 mutated but not in wild-type cells leading to mitotic
catastrophe, defective cell division and apoptosis. STAG1 inactivation inhibits
the proliferation of STAG2 mutated but not wild-type bladder cancer and Ewing
sarcoma cell lines. Restoration of STAG2 expression in a mutated bladder cancer
model alleviates the dependency on STAG1. Thus, STAG1 and STAG2 support sister
chromatid cohesion to redundantly ensure cell survival. STAG1 represents a
vulnerability of cancer cells carrying mutations in the major emerging tumor
suppressor STAG2 across different cancer contexts. Exploiting synthetic lethal
interactions to target recurrent cohesin mutations in cancer, e.g. by inhibiting
STAG1, holds the promise for the development of selective therapeutics.
PMID- 28691906
TI - Direct carotid access for endovascular management of acute ischaemic stroke.
PMID- 28691905
TI - Effects of dopamine on reinforcement learning and consolidation in Parkinson's
disease.
AB - Emerging evidence suggests that dopamine may modulate learning and memory with
important implications for understanding the neurobiology of memory and future
therapeutic targeting. An influential hypothesis posits that dopamine biases
reinforcement learning. More recent data also suggest an influence during both
consolidation and retrieval. Eighteen Parkinson's disease patients learned
through feedback ON or OFF medication, with memory tested 24 hr later ON or OFF
medication (4 conditions, within-subjects design with matched healthy control
group). Patients OFF medication during learning decreased in memory accuracy over
the following 24 hr. In contrast to previous studies, however, dopaminergic
medication during learning and testing did not affect expression of positive or
negative reinforcement. Two further experiments were run without the 24 hr delay,
but they too failed to reproduce effects of dopaminergic medication on
reinforcement learning. While supportive of a dopaminergic role in consolidation,
this study failed to replicate previous findings on reinforcement learning.
PMID- 28691907
TI - Prognosis of deferred non-culprit lesions according to fractional flow reserve in
patients with acute coronary syndrome.
AB - AIMS: There are limited data on the prognosis of deferred non-culprit lesions in
patients with acute coronary syndrome (ACS) based on fractional flow reserve
(FFR). We aimed to investigate the prognosis of deferred non-culprit lesions in
ACS patients, compared with deferred lesions in patients with stable coronary
artery disease (SCAD), on the basis of FFR. METHODS AND RESULTS: The clinical
outcomes of 449 non-culprit lesions (301 patients with ACS) were compared with
2,484 lesions (1,295 patients with SCAD) in which revascularisation was deferred
on the basis of a high FFR (>0.80). The primary outcome was major adverse cardiac
events (MACE), a composite of cardiac death, target vessel-related myocardial
infarction (MI) and ischaemia-driven revascularisation. Among the ACS population,
65.8% presented with unstable angina and 34.2% with non-ST-segment elevation MI.
Mean angiographic percent diameter stenosis and FFR of the deferred lesions were
39.3+/-15.0% and 0.92+/-0.06, respectively. During the median follow-up duration
of 722.0 days, the deferred non-culprit lesions of ACS patients showed a
significantly higher rate of MACE (3.8% vs. 1.6%, HRadj 2.97, 95% CI: 1.23-7.17,
p=0.016), mainly driven by the higher rate of ischaemia-driven revascularisation
(2.8% vs. 1.1%, HRadj 3.39, 95% CI: 1.29-8.92, p=0.013) than the deferred lesions
in SCAD patients. Regardless of the range of FFR in the deferred lesions (0.81
0.85, 0.86-0.90, 0.91-0.95, and 0.95-1.00), non-culprit lesions of ACS showed a
more than twofold higher rate of MACE than that of SCAD. In a multivariable
marginal Cox model, ACS was the most powerful independent predictor of MACE
(HRadj 2.74, 95% CI: 1.13-6.64, p=0.026). CONCLUSIONS: Compared to the deferred
lesions of SCAD patients, deferred non-culprit lesions of ACS on the basis of FFR
showed a higher rate of clinical events, regardless of FFR range.
PMID- 28691908
TI - High-pressure balloon fracturing of small dysfunctional Mitroflow bioprostheses
facilitates transcatheter aortic valve-in-valve implantation.
AB - AIMS: Transcatheter valve-in-valve (VIV) implantation is usually discouraged in
small surgical tissue valves. We report our first ten cases of fracturing small
dysfunctional Mitroflow bioprostheses by high-pressure balloon dilatation to
increase the internal diameter of the surgical valve before VIV (BF-VIV). METHODS
AND RESULTS: BF-VIV was performed in 10 patients (mean age 84+/-4 years) with
failing Mitroflow valves size 19 mm (n=3, threshold of fracture 15 atm) and 21 mm
(n=7, threshold of fracture 13 atm). An Edwards SAPIEN 3 or XT 20 mm or 23 mm
transcatheter valve was implanted inside the fractured Mitroflow bioprosthesis.
The procedure improved aortic valve area (0.7+/-0.3 vs. 1.1+/-0.3 cm2, p=0.001),
reduced peak aortic valve gradient (66+/-27 vs. 29+/-7 mmHg, p=0.002), resolved
aortic regurgitation and improved patients' NYHA functional class (p=0.005). One
patient had a minor stroke with complete resolution of symptoms and another
patient required a pacemaker due to AV block. All patients were still alive at
the end of follow-up (438+/-255 days). CONCLUSIONS: Initial experience with
transcatheter BF-VIV suggests that this method is feasible and safe, and that it
improves aortic valve haemodynamics and clinical functional capacity. BF-VIV is a
promising alternative to repeat surgery in patients with small failing Mitroflow
bioprostheses.
PMID- 28691909
TI - Fracturing mechanics before valve-in-valve therapy of small aortic bioprosthetic
heart valves.
AB - AIMS: Patients with degraded bioprosthetic heart valves (BHV) who are not
candidates for valve replacement may benefit from transcatheter valve-in-valve
(VIV) therapy. However, in smaller-sized surgical BHV the resultant orifice may
become too narrow. To overcome this, the valve frame can be fractured by a high
pressure balloon prior to VIV. However, knowledge on fracture pressures and
mechanics are prerequisites. The aim of this study was to identify the fracture
pressures needed in BHV, and to describe the fracture mechanics. METHODS AND
RESULTS: Commonly used BHV of small sizes were mounted on a high-pressure balloon
situated in a biplane fluoroscopic system with a high-speed camera. The instant
of fracture was captured along with the balloon pressure. The valves were
inspected for material protrusion and later dissected for fracture zone
investigation and description. The valves with a polymer frame fractured at a
lower pressure (8-10 atm) than those with a metal stent (19-26 atm). None of the
fractured valves had elements protruding. CONCLUSIONS: VIV procedures in small
sized BHV may be performed after prior fracture of the valve frame by high
pressure balloon dilatation. This study provides tentative guidelines for
expected balloon sizes and pressures for valve fracturing.
PMID- 28691910
TI - Transcatheter aortic valve implantation for mixed versus pure stenotic aortic
valve disease.
AB - AIMS: In addition to patients with pure/predominant aortic stenosis (PAS), real
world transcatheter aortic valve implantation (TAVI) referrals include patients
with mixed aortic valve disease (MAVD; severe stenosis+moderate-severe
regurgitation). We sought to compare TAVI outcomes in patients with MAVD vs. PAS.
METHODS AND RESULTS: Out of 793 consecutive patients undergoing TAVI, 106 (13.4%)
had MAVD. Patients with MAVD were younger and had a higher operative risk, a more
severe adverse cardiac remodelling, and a worse functional status than patients
with PAS. Moderate-severe prosthetic valve regurgitation (PVR) was significantly
more frequent in patients with MAVD than in patients with PAS (15.7% vs. 3.6%,
p=0.003), even after propensity-score and multivariable adjustments. Moderate
severe PVR was associated with increased one-year mortality in patients with PAS
(log-rank p=0.002), but not in patients with MAVD (log-rank p=0.27). Eventually,
all-cause and cardiac mortality as well as the functional capacity were similar
in the two study groups up to one year. CONCLUSIONS: A significant proportion of
patients referred for TAVI in a real-world registry has MAVD. Moderate-severe AR
at baseline can influence the rate and modify the clinical sequelae of post-TAVI
PVR. Eventually, clinical outcomes in patients with MAVD are comparable to those
in patients with PAS in the acute and midterm phases, in spite of a baseline
higher risk. MAVD should not be considered a contraindication for TAVI.
PMID- 28691911
TI - A novel synchronised diastolic injection method to reduce contrast volume during
aortography for aortic regurgitation assessment: in vitro experiment of a
transcatheter heart valve model.
AB - AIMS: In the minimalist transcatheter aortic valve implantation (TAVI) era, the
usage of transoesophageal echocardiography has become restricted. Conversely,
aortography has gained clinical ground in quantifying prosthetic valve
regurgitation (PVR) during the procedure. In a mock circulation system, we sought
to compare the contrast volume required and the accuracy of aortographic
videodensitometric PVR assessment using a synchronised diastolic and standard
(non-synchronised) injection aortography. METHODS AND RESULTS: Synchronised
diastolic injection triggered by the signal stemming from the mock circulation
was compared with standard non-synchronised injection. A transcatheter heart
valve was implanted and was deformed step by step by advancing a screw
perpendicularly to the cage of the valve in order to create increasing PVR.
Quantitative measurement of PVR was derived from time-density curves of both a
reference area (aortic root) and a region of interest (left ventricle) developed
by a videodensitometric software. The volume of contrast required for the
synchronised diastolic injection was significantly less than in the non
synchronised injection (8.1 [7.9-8.5] ml vs. 19.4 [19.2-19.9] ml, p<0.001). The
correlation between the two methods was substantial (Spearman's coefficient rho
ranging from 0.991 to 0.968). Intraobserver intra-class correlation coefficient
for both methods of injection was 0.999 (95% CI: 0.996-1.000) for the
synchronised diastolic and 0.999 (95% CI: 0.996-1.000) for the non-synchronised
injection group. The mean difference in the rating was 0.17% and limits of
agreement were +/-1.64% for both groups. CONCLUSIONS: A short synchronised
diastolic injection enables contrast volume reduction during aortography without
compromising the accuracy of the quantitative assessment of PVR using
videodensitometry.
PMID- 28691912
TI - Stepwise optimisation of balloon pulmonary angioplasty in a patient with severe
non-operable chronic thromboembolic pulmonary hypertension.
PMID- 28691913
TI - Real-time fusion of echocardiography and fluoroscopy allowing successful
implantation of a WATCHMAN device without contrast injection.
PMID- 28691914
TI - Residual leaks following percutaneous left atrial appendage occlusion: assessment
and management implications.
AB - Left atrial appendage (LAA) closure for stroke prevention in the setting of non
valvular atrial fibrillation is an alternative to oral anticoagulation in
patients with increased bleeding risk. It allows similar reduction in
thromboembolic events, in particular stroke, compared to warfarin. A common
clinical dilemma is the management of patients with peri-device leak after LAA
occlusion. This has been documented in both percutaneous as well as surgical
approaches. The specific definitions of leak severity, and the longer-term
clinical implications are poorly understood. Here we review the mechanisms of
incomplete occlusion for the different percutaneous closure devices, the data
regarding thromboembolic risk in patients with incomplete appendage closure for
both percutaneous and surgical strategies, and provide recommendations for
management in these patients.
PMID- 28691915
TI - Forensic individual age estimation with DNA: From initial approaches to
methylation tests.
AB - Individual age estimation is a key factor in forensic science analysis that can
provide very useful information applicable to criminal, legal, and
anthropological investigations. Forensic age inference was initially based on
morphological inspection or radiography and only later began to adopt molecular
approaches. However, a lack of accuracy or technical problems hampered the
introduction of these DNA-based methodologies in casework analysis. A turning
point occurred when the epigenetic signature of DNA methylation was observed to
gradually change during an individual's lifespan. In the last four years, the
number of publications reporting DNA methylation age-correlated changes has
gradually risen and the forensic community now has a range of age methylation
tests applicable to forensic casework. Most forensic age predictor models have
been developed based on blood DNA samples, but additional tissues are now also
being explored. This review assesses the most widely adopted genes harboring
methylation sites, detection technologies, statistical age-predictive analyses,
and potential causes of variation in age estimates. Despite the need for further
work to improve predictive accuracy and establishing a broader range of tissues
for which tests can analyze the most appropriate methylation sites, several
forensic age predictors have now been reported that provide consistency in their
prediction accuracies (predictive error of +/-4 years); this makes them
compelling tools with the potential to contribute key information to help guide
criminal investigations.
PMID- 28691916
TI - Social and ethical aspects of forensic genetics: A critical review.
AB - This review describes the social and ethical responses to the history of
innovations in forensic genetics and their application to criminal
investigations. Following an outline of the three recurrent social perspectives
that have informed these responses (crime management, due process, and genetic
surveillance), it goes on to introduce the repertoire of ethical considerations
by describing a series of key reports that have shaped subsequent commentaries on
forensic DNA profiling and databasing. Four major ethical concerns form the focus
of the remainder of the paper (dignity, privacy, justice, and social solidarity),
and key features of forensic genetic practice are examined in the light of these
concerns. The paper concludes with a discussion of the concept of
"proportionality" as a resource for balancing the social and ethical risks and
benefits of the use of forensic genetics in support of criminal justice.
PMID- 28691917
TI - The effect of disorder of small spheres on the photonic properties of the inverse
binary NaCl-like structure.
AB - Inverse opal structures are experimentally realisable photonic band gap
materials. They suffer from the drawback of possessing band gaps that are
extremely susceptible to structural disorders. A binary colloidal NaCl lattice,
which is also experimentally realisable, is a promising alternative to these
opals. In this work, we systematically analyse the effect of structural disorder
of the small spheres on the photonic properties of an inverse binary NaCl lattice
with a size ratio of 0.30 between the small and large spheres. The types of
structural disorders studied include the position of the small spheres in the
octahedral void of the large spheres, polydispersity in size of the small
spheres, and the fraction of small spheres in the crystal. We find a low
susceptibility of the band gap of the inverse NaCl lattice to the disorder of the
small spheres.
PMID- 28691918
TI - Optical fingerprint of non-covalently functionalized transition metal
dichalcogenides.
AB - Atomically thin transition metal dichalcogenides (TMDs) hold promising potential
for applications in optoelectronics. Due to their direct band gap and the
extraordinarily strong Coulomb interaction, TMDs exhibit efficient light-matter
coupling and tightly bound excitons. Moreover, large spin orbit coupling in
combination with circular dichroism allows for spin and valley selective optical
excitation. As atomically thin materials, they are very sensitive to changes in
the surrounding environment. This motivates a functionalization approach, where
external molecules are adsorbed to the materials surface to tailor its optical
properties. Here, we apply the density matrix theory to investigate the potential
of non-covalently functionalized monolayer TMDs. Considering exemplary molecules
with a strong dipole moment, we predict spectral redshifts and the appearance of
an additional side peak in the absorption spectrum of functionalized TMDs. We
show that the molecular characteristics, e.g. coverage, orientation and dipole
moment, crucially influence the optical properties of TMDs, leaving a unique
optical fingerprint in the absorption spectrum. Furthermore, we find that the
molecular dipole moments open a channel for coherent intervalley coupling between
the high-symmetry K and [Formula: see text] points which may create new
possibilities for spin-valleytronics application.
PMID- 28691919
TI - Modeling and analysis of a meso-hydraulic climbing robot with artificial muscle
actuation.
AB - This paper presents a fully coupled electro-hydraulic model of a bio-inspired
climbing robot actuated by fluidic artificial muscles (FAMs). This analysis
expands upon previous FAM literature by considering not only the force and
contraction characteristics of the actuator, but the complete hydraulic and
electromechanical circuits as well as the dynamics of the climbing robot. This
analysis allows modeling of the time-varying applied pressure, electrical
current, and actuator contraction for accurate prediction of the robot motion,
energy consumption, and mechanical work output. The developed model is first
validated against mechanical and electrical data collected from a proof-of
concept prototype robot. The model is then employed to study the system-level
sensitivities of the robot locomotion efficiency and average climbing speed to
several design and operating parameters. The results of this analysis demonstrate
that considering only the transduction efficiency of the FAM actuators is
insufficient to maximize the efficiency of the complete robot, and that a
holistic approach can lead to significant improvements in performance.
PMID- 28691920
TI - Artificial Manduca sexta forewings for flapping-wing micro aerial vehicles: how
wing structure affects performance.
AB - A novel approach to fabricating and testing artificial insect wings has been
developed. Utilizing these new techniques, locally harvested hawk moth (Manduca
sexta) forewings are compared to engineered forewings with varying wing
structures. A number of small, flexible engineered forewings were fabricated with
identical planform size and shape but with variations in camber, ribbing,
thickness and composition. A series of static and dynamic assessments compares
the forewings in terms of structure and performance. Data from these experiments
show that the fabrication method can produce artificial forewings with similar
properties to that of M. sexta. Flexural stiffness (EI) data shows a maximum
percent difference of 41% between the left and right natural M. sexta forewings,
whereas engineered forewings have a maximum percent difference of 18%. When
deflection is induced from the ventral side of the forewing, EI values are at
least 9.1% higher than when it is induced from the dorsal side. According to
simulations, approximately 57% of this difference can be attributed to the camber
of the forewings. Fabricated forewings produced comparable amounts of lift to
natural M. sexta forewings (1.00 gF and 0.96 gF at 25 Hz flapping frequency
respectively).
PMID- 28691921
TI - Application of the Lany-Zunger polaron correction for calculating surface charge
trapping.
AB - Defect calculations, using density functional theory in a local or semi-local
approximation, in transition metal oxides are severely handicapped by the
electron self-interaction error. The underestimation of the band gap may cause
incorrect occupation of defect states and wrong formation energies, and the
underestimated localization of the states disfavors the formation of small
polarons. These problems can be avoided by using higher level approximations (GW
or a correctly chosen hybrid functional), but those methods are computationally
too expensive to be used for calculating surface defects in a periodic slab
model. Lany and Zunger have suggested a convenient (low-cost) solution for
solving the band-gap and charge delocalization problem, by applying a correction
scheme to the standard local or semi-local approximations. Most importantly, the
linearity of the total energy as a function of the fractional occupation numbers,
is restored, leading to the fulfillment of the generalized Koopmans' theorem. The
method works well in the bulk but, as we show here, it is not accurate on the
surface due to the different screening environment. We also show that by making
the atom- and angular-momentum dependent parameters of the Lany-Zunger polaron
correction also coordination dependent, it is possible to correctly describe
charge trapping in small polaron states on the anatase (1 0 1) and rutile (1 1 0)
surfaces at a low computational cost.
PMID- 28691922
TI - Role of atom redeposition during rising ion flux in ion-induced nanodot self
assembly on GaSb surfaces.
AB - In this study, a bottom-up approach of ion irradiation from hot cathode DC
discharge plasma was used to investigate the role of energetic ion flux on the
self-assembly of GaSb nanodots (NDs) at normal incidence. It was observed that,
when increasing the flux in the range of 1014-1015 ions cm-2 s-1, the lateral
dimension and root mean square (RMS) roughness of NDs is reduced even at constant
temperature conditions in the ion energy range from 400-800 eV. The evolution of
the surface morphology for different flux regimes is observed in a numerical
integration simulation using the nonlinear isotropic damped Kuramoto-Sivashinsky
(DKS) equation. By introducing a redeposition term, the DKS equation is found to
be in good qualitative agreement with the experimental results. We have
demonstrated the linear dependency of the redeposition coefficient on the ion
flux and also reported the nonlinear dependency on the thermal diffusion
coefficient, transition time, and characteristic length with the flux. In
accordance with the nonlinearity, we have also discussed the effect of the
variation of the ion flux on the RMS roughness and lateral dimension of NDs.
PMID- 28691923
TI - In situ self-assembly of polarizing chromogen nanofibers catalyzed with hybrid
films of gold nanoparticles and cellulose.
AB - Hybrid materials of metal nanoparticles and biopolymers with catalytic properties
are very promising to be used as detectors in biochemical reactions. In this
work, the catalytic properties and relevant in situ self-assembly abilities of
hybrid films of gold nanoparticles (GNPs) and cellulose for the oxidation of
benign chromogen 3,3',5,5'-tetramethylbenzidine (TMB) with hydrogen peroxide
(H2O2) are revealed for the first time. The peroxidase-like properties of hybrid
films are inherited from those of colloidal GNPs and increase with their contents
of GNPs. It is discovered that the oxidized products of TMB grow in situ and
assemble into rod-like and tumbleweed-like nanofiber assemblies on hybrid films.
The rod-like nanofibers show a magnificent polarizing phenomenon under polarized
light because of polycrystalline globular nanoparticles inside. The in situ self
assembly of polarizing nanofibers of chromogen catalyzed with hybrid films
creates an opportunity for the synthesis of novel organic nanomaterials and the
enhanced detection of biochemical products under polarized light.
PMID- 28691924
TI - Theoretical studies on lattice-oriented growth of single-walled carbon nanotubes
on sapphire.
AB - Due to their excellent mechanical and electrical properties, single-walled carbon
nanotubes (SWNTs) can find broad applications in many areas, such as field-effect
transistors, logic circuits, sensors and flexible electronics. High-density,
horizontally aligned arrays of SWNTs are essential for high performance
electronics. Many experimental studies have demonstrated that chemical vapor
deposition growth of nanotubes on crystalline substrates such as sapphire offers
a promising route to achieve such dense, perfectly aligned arrays. In this work,
a theoretical study is performed to quantitatively understand the van der Waals
interactions between SWNTs and sapphire substrates. The energetically preferred
alignment directions of SWNTs on A-, R- and M-planes and the random alignment on
the C-plane predicted by this study are all in good agreement with experiments.
It is also shown that smaller SWNTs have better alignment than larger SWNTs due
to their stronger interaction with sapphire substrate. The strong vdW
interactions along preferred alignment directions can be intuitively explained by
the nanoscale 'grooves' formed by atomic lattice structures on the surface of
sapphire. This study provides important insights to the controlled growth of
nanotubes and potentially other nanomaterials.
PMID- 28691925
TI - Design and analysis of aerodynamic force platforms for free flight studies.
AB - We describe and explain new advancements in the design of the aerodynamic force
platform, a novel instrument that can directly measure the aerodynamic forces
generated by freely flying animals and robots. Such in vivo recordings are
essential to better understand the precise aerodynamic function of flapping wings
in nature, which can critically inform the design of new bioinspired robots. By
designing the aerodynamic force platform to be stiff yet lightweight, the natural
frequencies of all structural components can be made over five times greater than
the frequencies of interest. The associated high-frequency noise can then be
filtered out during post-processing to obtain accurate and precise force
recordings. We illustrate these abilities by measuring the aerodynamic forces
generated by a freely flying bird. The design principles can also be translated
to other fluid media. This offers an opportunity to perform high-throughput, real
time, non-intrusive, and in vivo comparative biomechanical measurements of force
generation by locomoting animals and robots. These recordings can include complex
bimodal terrestrial, aquatic, and aerial behaviors, which will help advance the
fields of experimental biology and bioinspired design.
PMID- 28691926
TI - Low temperature solid-state wetting and formation of nanowelds in silver
nanowires.
AB - This article focuses on the microscopic mechanism of thermally induced nanoweld
formation between silver nanowires (AgNWs) which is a key process for improving
electrical conductivity in NW networks employed for transparent electrodes.
Focused ion beam sectioning and transmission electron microscopy were applied in
order to elucidate the atomic structure of a welded NW including measurement of
the wetting contact angle and characterization of defect structure with atomic
accuracy, which provides fundamental information on the welding mechanism.
Crystal lattice strain, obtained by direct evaluation of atomic column
displacements in high resolution scanning transmission electron microscopy
images, was shown to be non-uniform among the five twin segments of the AgNW
pentagonal structure. It was found that the pentagonal cross-sectional morphology
of AgNWs has a dominant effect on the formation of nanowelds by controlling
initial wetting as well as diffusion of Ag atoms between the NWs. Due to complete
solid-state wetting, at an angle of ~4.8 degrees , the welding process starts
with homoepitaxial nucleation of an initial Ag layer on (100) surface facets,
considered to have an infinitely large radius of curvature. However, the strong
driving force for this process due to the Gibbs-Thomson effect, requires the NW
contact to occur through the corner of the pentagonal cross-section of the second
NW providing a small radius of curvature. After the initial layer is formed, the
welded zone continues to grow and extends out epitaxially to the neighboring twin
segments.
PMID- 28691927
TI - Ubiquitination of tumor suppressor PML regulates prometastatic and
immunosuppressive tumor microenvironment.
AB - The tumor microenvironment plays an important role in tumor growth and
metastasis. However, the mechanism by which tumor cells regulate the cell and non
cell constituents of surrounding stroma remains incompletely understood.
Promyelocytic leukemia (PML) is a pleiotropic tumor suppressor, but its role in
tumor microenvironment regulation is poorly characterized. PML is frequently
downregulated in many cancer types, including lung cancer. Here, we identify a
PML ubiquitination pathway that is mediated by WD repeat 4-containing cullin-RING
ubiquitin ligase 4 (CRL4WDR4). Clinically, this PML degradation pathway is
hyperactivated in lung cancer and correlates with poor prognosis. The WDR4/PML
axis induces a set of cell-surface or secreted factors, including CD73, urokinase
type plasminogen activator receptor (uPAR), and serum amyloid A2 (SAA2), which
elicit paracrine effects to stimulate migration, invasion, and metastasis in
multiple lung cancer models. In xenograft and genetically engineered mouse
models, the WDR4/PML axis elevates intratumoral Tregs and M2-like macrophages and
reduces CD8+ T cells to promote lung tumor growth. These immunosuppressive
effects were all reversed by CD73 blockade. Our study identifies WDR4 as an
oncoprotein that negatively regulates PML via ubiquitination to promote lung
cancer progression by fostering an immunosuppressive and prometastatic tumor
microenvironment, suggesting the potential of immune-modulatory approaches for
treating lung cancer with aberrant PML degradation.
PMID- 28691928
TI - Mutations in 5-methylcytosine oxidase TET2 and RhoA cooperatively disrupt T cell
homeostasis.
AB - Angioimmunoblastic T cell lymphoma (AITL) represents a distinct, aggressive form
of peripheral T cell lymphoma with a dismal prognosis. Recent exome sequencing in
patients with AITL has revealed the frequent coexistence of somatic mutations in
the Rho GTPase RhoA (RhoAG17V) and loss-of-function mutations in the 5
methylcytosine oxidase TET2. Here, we have demonstrated that TET2 loss and
RhoAG17V expression in mature murine T cells cooperatively cause abnormal CD4+ T
cell proliferation and differentiation by perturbing FoxO1 gene expression,
phosphorylation, and subcellular localization, an abnormality that is also
detected in human primary AITL tumor samples. Reexpression of FoxO1 attenuated
aberrant immune responses induced in mouse models adoptively transferred with T
cells and bearing genetic lesions in both TET2 and RhoA. Our findings suggest a
mutational cooperativity between epigenetic factors and GTPases in adult CD4+ T
cells that may account for immunoinflammatory responses associated with AITL
patients.
PMID- 28691929
TI - Biallelic mutations in the ubiquitin ligase RFWD3 cause Fanconi anemia.
AB - The WD40-containing E3 ubiquitin ligase RFWD3 has been recently linked to the
repair of DNA damage by homologous recombination (HR). Here we have shown that an
RFWD3 mutation within the WD40 domain is connected to the genetic disease Fanconi
anemia (FA). An individual presented with congenital abnormalities characteristic
of FA. Cells from the patient carrying the compound heterozygous mutations
c.205_206dupCC and c.1916T>A in RFWD3 showed increased sensitivity to DNA
interstrand cross-linking agents in terms of increased chromosomal breakage,
reduced survival, and cell cycle arrest in G2 phase. The cellular phenotype was
mirrored in genetically engineered human and avian cells by inactivation of RFWD3
or introduction of the patient-derived missense mutation, and the phenotype was
rescued by expression of wild-type RFWD3 protein. HR was disrupted in RFWD3
mutant cells as a result of impaired relocation of mutant RFWD3 to chromatin and
defective physical interaction with replication protein A. Rfwd3 knockout mice
appear to have increased embryonic lethality, are subfertile, show ovarian and
testicular atrophy, and have a reduced lifespan resembling that of other FA mouse
models. Although RFWD3 mutations have thus far been detected in a single child
with FA, we propose RFWD3 as an FA gene, FANCW, supported by cellular paradigm
systems and an animal model.
PMID- 28691932
TI - Effects of the Smartphone Application "Safe Patients" on Knowledge of Patient
Safety Issues Among Surgical Patients.
AB - Recently, the patient's role in preventing adverse events has been emphasized.
Patients who are more knowledgeable about safety issues are more likely to engage
in safety initiatives. Therefore, nurses need to develop techniques and tools
that increase patients' knowledge in preventing adverse events. For this reason,
an educational smartphone application for patient safety called "Safe Patients"
was developed through an iterative process involving a literature review, expert
consultations, and pilot testing of the application. To determine the effect of
"Safe Patients," it was implemented for patients in surgical units in a tertiary
hospital in South Korea. The change in patients' knowledge about patient safety
was measured using seven true/false questions developed in this study. A one
group pretest and posttest design was used, and a total of 123 of 190 possible
participants were tested. The percentage of correct answers significantly
increased from 64.5% to 75.8% (P < .001) after implementation of the "Safe
Patients" application. This study demonstrated that the application "Safe
Patients" could effectively improve patients' knowledge of safety issues. This
will ultimately empower patients to engage in safe practices and prevent adverse
events related to surgery.
PMID- 28691930
TI - Ly6Clo monocytes drive immunosuppression and confer resistance to anti-VEGFR2
cancer therapy.
AB - Current anti-VEGF therapies for colorectal cancer (CRC) provide limited survival
benefit, as tumors rapidly develop resistance to these agents. Here, we have
uncovered an immunosuppressive role for nonclassical Ly6Clo monocytes that
mediates resistance to anti-VEGFR2 treatment. We found that the chemokine CX3CL1
was upregulated in both human and murine tumors following VEGF signaling
blockade, resulting in recruitment of CX3CR1+Ly6Clo monocytes into the tumor. We
also found that treatment with VEGFA reduced expression of CX3CL1 in endothelial
cells in vitro. Intravital microscopy revealed that CX3CR1 is critical for Ly6Clo
monocyte transmigration across the endothelium in murine CRC tumors. Moreover,
Ly6Clo monocytes recruit Ly6G+ neutrophils via CXCL5 and produce IL-10, which
inhibits adaptive immunity. Preventing Ly6Clo monocyte or Ly6G+ neutrophil
infiltration into tumors enhanced inhibition of tumor growth with anti-VEGFR2
therapy. Furthermore, a gene therapy using a nanoparticle formulated with an
siRNA against CX3CL1 reduced Ly6Clo monocyte recruitment and improved outcome of
anti-VEGFR2 therapy in mouse CRCs. Our study unveils an immunosuppressive
function of Ly6Clo monocytes that, to our knowledge, has yet to be reported in
any context. We also reveal molecular mechanisms underlying antiangiogenic
treatment resistance, suggesting potential immunomodulatory strategies to enhance
the long-term clinical outcome of anti-VEGF therapies.
PMID- 28691931
TI - Gentamicin induces functional type VII collagen in recessive dystrophic
epidermolysis bullosa patients.
AB - BACKGROUND: Recessive dystrophic epidermolysis bullosa (RDEB) is an incurable
disease caused by mutations in the gene encoding type VII collagen, the major
component of anchoring fibrils (AF). We previously demonstrated that gentamicin
produced functional type VII collagen in RDEB cells harboring nonsense mutations.
Herein, we determined whether topical or intradermal gentamicin administration
induces type VII collagen and AFs in RDEB patients. METHODS: A double-blind,
placebo-controlled pilot trial assessed safety and efficacy of topical and
intradermal gentamicin in 5 RDEB patients with nonsense mutations. The topical
arm tested 0.1% gentamicin ointment or placebo application 3 times daily at 2
open erosion sites for 2 weeks. The intradermal arm tested daily intradermal
injection of gentamicin solution (8 mg) or placebo into 2 intact skin sites for 2
days in 4 of 5 patients. Primary outcomes were induction of type VII collagen and
AFs at the test sites and safety assessment. A secondary outcome assessed wound
closure of topically treated erosions. RESULTS: Both topical and intradermal
gentamicin administration induced type VII collagen and AFs at the dermal
epidermal junction of treatment sites. Newly created type VII collagen varied
from 20% to 165% of that expressed in normal human skin and persisted for 3
months. Topical gentamicin corrected dermal-epidermal separation, improved wound
closure, and reduced blister formation. There were no untoward side effects from
gentamicin treatments. Type VII collagen induction did not generate anti-type VII
collagen autoantibodies in patients' blood or skin. CONCLUSION: Topical and
intradermal gentamicin suppresses nonsense mutations and induces type VII
collagen and AFs in RDEB patients. Gentamicin therapy may provide a readily
available treatment for RDEB patients with nonsense mutations. TRIAL
REGISTRATION: ClinicalTrials.gov NCT02698735. FUNDING: Epidermolysis Bullosa
Research Partnership, Epidermolysis Bullosa Medical Research Foundation, NIH, and
VA Merit Award.
PMID- 28691933
TI - Cost of Ulcerative Colitis in Quebec, Canada: A Retrospective Cohort Study.
AB - BACKGROUND: Ulcerative colitis (UC) is associated with significant health care
utilization and costs. We assessed UC direct medical costs in Quebec, Canada, in
2 time periods (1998-2004 and 2005-2011) and determined changes over time.
METHODS: Because the introduction of anti-tumor necrosis factor alpha may have
influenced the UC cost, we used the Quebec health services administrative
databases and the same inclusion criteria to create 2 separate UC cohorts, before
(1998-2004) and after (2005-2011) anti-tumor necrosis factor alpha introduction.
RESULTS: The postcohort included 801 patients and the precohort 716 patients.
Overall, cohorts were predominately women and were comparable in terms of
patient's demographics and comorbidities. Corticosteroid use, emergency
department visits and hospitalizations for colectomies, and other
gastrointestinal disorders were fewer in the postcohort versus precohort. The
median daily cost (interquartile range) was $16.96 ($6.80-$48.16) for the
postcohort and $18.65 ($7.82-$53.31) for the precohort. In generalized linear
models with log link and gamma distribution, the adjusted daily cost ratios (95%
confidence interval) in the postcohort versus precohort was 0.75 (0.67-0.85).
Older age at inclusion, low income, lower socioeconomic status, and previous use
of gastroprotective agents, antidepressants, and sulfasalazine, methotrexate, or
cyclosporine were associated with increased costs. Women and those who visited a
gastroenterologist in the previous year incurred lower costs. CONCLUSIONS: The
mean UC daily cost decreased from 2005 to 2011 as compared to 1998 to 2004
because of a decrease in rates of colectomy and other gastrointestinal
hospitalizations and emergency department visits. Further investigation is
required to determine the reasons for these changes.
PMID- 28691934
TI - Comparison of Different Hearing Aid Prescriptions for Children.
AB - OBJECTIVES: To assess whether there are significant differences between speech
scores for different hearing aid prescription methods, specifically DSL i/o, DSL
V, and NAL-NL1, using age-appropriate closed- and open-set speech tests with
young children, designed to avoid floor and ceiling effects. DESIGN: Participants
were 44 children with moderate or severe bilateral hearing loss, 8 aged 2 to 3
years, 15 aged 4 to 5 years, and 21 aged 6 to 9 years. Children wore bilateral
hearing aids fitted with each prescription method in turn in a balanced double
blind design. The speech tests used with each child (and for some tests the
levels) were chosen so as to avoid floor and ceiling effects. For the closed-set
tests, the level used was selected for each child based on their hearing loss.
The tests used were: (1) The closed-set Consonant Confusion Test of word
identification; (2) The closed-set Chear Auditory Perception Test (CAPT) of word
identification. This has separate sections assessing discrimination of consonants
and vowels and detection of consonants; (3) The open-set Cambridge Auditory Word
Lists for testing word identification at levels of 50 and 65 dBA, utilizing 10
consonant-vowel-consonant real words that are likely to be familiar to children
aged 3 years or older; (4) The open-set Common Phrases Test to measure the speech
reception threshold in quiet; (5) Measurement of the levels required for
identification of the Ling 5 sounds, using a recording of the sounds made at the
University of Western Ontario. RESULTS: Scores for the Consonant Confusion Test
and CAPT consonant discrimination and consonant detection were lower for the NAL
NL1 prescription than for the DSL prescriptions. Scores for the CAPT vowel-in
noise discrimination test were higher for DSL V than for either of the other
prescriptions. Scores for the Cambridge Auditory Word Lists did not differ across
prescriptions for the level of 65 dBA, but were lower for the NAL-NL1
prescription than for either of the DSL prescriptions for the level of 50 dBA.
The speech reception threshold measured using the Common Phrases Test and the
levels required for identification of the Ling 5 sounds were higher (worse) for
the NAL-NL1 prescription than for the DSL prescriptions. CONCLUSIONS: The higher
gains prescribed by the DSL i/o and DSL V prescription methods relative to NAL
NL1 led to significantly better detection and discrimination of low-level speech
sounds.
PMID- 28691936
TI - National Variation in the Use of Tracheostomy in Patients With Congenital Heart
Disease.
AB - OBJECTIVES: The postsurgical care of children with congenital heart disease may
be complicated by the need for cardiorespiratory support, including tracheostomy.
The variation of the use of tracheostomy across multiple pediatric cardiac
surgical centers has not been defined. We describe multicenter variation in the
use of tracheostomy in children undergoing congenital heart surgery. DESIGN: We
retrospectively analyzed a multicenter cohort. SETTING: Pediatric Health
Information Systems database retrospective cohort. PATIENTS: Children less than
18 years who underwent both tracheostomy and cardiac surgery (1/04-6/14).
INTERVENTIONS: Univariate and multivariate statistics were performed, stratifying
by high (>= 75th percentile) and low (<= 25th percentile) tracheostomy volume and
adjusting for patient characteristics in multivariate models. MEASUREMENTS AND
MAIN RESULTS: Out of 123,510 hospitalizations involving cardiac surgery, 1,292
tracheostomies (1.2%) were performed (46 hospitals). The rate of tracheostomy
placement ranged from 0.3% to 2.5% with no difference in the rate of tracheostomy
placement between high and low tracheostomy use centers (p = 0.8). The median
time to tracheostomy was 63 days (interquartile range, 36-100), and there was no
difference between high- and low-tracheostomy centers. High-tracheostomy centers
had $420,000 lower hospital charges than low-volume centers (p = 0.03).
Tracheostomy day greater than the median (63 d), Risk Adjustment for Congenital
Heart Surgery-1 score 6, and extracorporeal membrane oxygenation were
significantly associated with adjusted increased odds of mortality. Later
hospital day of tracheostomy was associated with a $13,000/d increase in total
hospital charges (p < 0.001). CONCLUSIONS: Variation in the usage of tracheostomy
in infants and children undergoing congenital heart surgery exists across the
country. High-tracheostomy centers had lower hospital charges. Late tracheostomy
placement, higher congenital heart disease surgical risk, and extracorporeal
membrane oxygenation use are independent predictors of in-hospital mortality in
this population.
PMID- 28691937
TI - MACULAR ATROPHY AND MACULAR MORPHOLOGY IN AFLIBERCEPT-TREATED NEOVASCULAR AGE
RELATED MACULAR DEGENERATION.
AB - PURPOSE: To investigate the incidence and predictors of macular atrophy during
treatment with aflibercept for neovascular age-related macular degeneration in
Japanese patients. METHODS: This study included patients with treatment-naive
subfoveal neovascular age-related macular degeneration treated from December 2012
through January 2015. Patients were treated with bi-monthly aflibercept
injections after 3 monthly loading injections for the first year. Diagnosis of
retinal pigment epithelial atrophy was made based on color fundus photography,
spectral-domain optical coherence tomography, and fundus autofluorescence.
Baseline characteristics and morphological features were analyzed for their
association with the development of macular atrophy. RESULTS: This study included
123 eyes that had no baseline macular atrophy and treated with aflibercept
injections for 12 months. Thirteen eyes (10.6%) developed new macular atrophy at
12 months. Logistic regression analysis showed that the presence of intraretinal
fluid and thinner subfoveal choroidal thickness at baseline were associated with
the development of macular atrophy after aflibercept treatment. CONCLUSION:
Macular atrophy developed in about 10% of eyes with neovascular age-related
macular degeneration during 12 months of treatment with a fixed regimen of
aflibercept. Intraretinal fluid and subfoveal choroidal thickness seem to be
predictors for development of macular atrophy after anti-vascular endothelial
growth factor (VEGF) therapy.
PMID- 28691935
TI - Quality Improvement Initiatives in Sepsis in an Emerging Country: Does the
Institution's Main Source of Income Influence the Results? An Analysis of 21,103
Patients.
AB - OBJECTIVE: We aimed to assess the results of a quality improvement initiative in
sepsis in an emerging setting and to analyze it according to the institutions'
main source of income (public or private). DESIGN: Retrospective analysis of the
Latin American Sepsis Institute database from 2005 to 2014. SETTINGS: Brazilian
public and private institutions. PATIENTS: Patients with sepsis admitted in the
participant institutions. INTERVENTIONS: The quality improvement initiative was
based on a multifaceted intervention. The institutions were instructed to collect
data on 6-hour bundle compliance and outcomes in patients with sepsis in all
hospital settings. Outcomes and compliance was measured for eight periods of 6
months each, starting at the time of the enrollment in the intervention. The
primary outcomes were hospital mortality and compliance with 6-hour bundle.
MEASUREMENTS AND MAIN RESULTS: We included 21,103 patients; 9,032 from public
institutions and 12,071 from private institutions. Comparing the first period
with the eigth period, compliance with the 6-hour bundle increased from 13.5% to
58.2% in the private institutions (p < 0.0001) and from 7.4% to 15.7% in the
public institutions (p < 0.0001). Mortality rates significantly decreased
throughout the program in private institutions, from 47.6% to 27.2% in the eighth
period (adjusted odds ratio, 0.45; 95% CI, 0.32-0.64). However, in the public
hospitals, mortality diminished significantly only in the first two periods.
CONCLUSION: This quality improvement initiative in sepsis in an emerging country
was associated with a reduction in mortality and with improved compliance with
quality indicators. However, this reduction was sustained only in private
institutions.
PMID- 28691938
TI - Genetic Versus Epigenetic BRCA1 Silencing Pathways: Clinical Effects in Primary
Ovarian Cancer Patients: A Study of the Tumor Bank Ovarian Cancer Consortium.
AB - OBJECTIVES: The aim of the present study was to assess in a large cohort of
primary epithelial ovarian cancer patients the incidence and the clinical effect
of BRCA1 genetic and epigenetic silencing mechanisms. METHODS: A total of 188
primary epithelial ovarian cancer patients, treated between 2000 and 2011 at the
Charite University Hospital of Berlin, were included. The patients' tumor and
blood samples were obtained from the Tumor Bank Ovarian Cancer Network (www.toc
network.de). Direct sequencing of BRCA1 exon 11 was performed to detect germline
mutations, whereas tumor samples were assessed for BRCA1 promoter
hypermethylation by bisulphite-converted methylation-specific polymerase chain
reaction. Basing on their BRCA1 status, patients were compared regarding
clinicopathological variables and survival. RESULTS: Twenty-one patients (11.2%)
showed hypermethylation in BRCA1 promoter (HMB), and 18 patients (9.6%) presented
germline mutations in BRCA1 exon 11 (GMB). Patients with HMB showed a
significantly younger age at diagnosis compared with BRCA1 wild type (BWT)
patients (54 vs 61 years, P = 0.045), and both GMB and HMB patients were more
likely to have high-grade serous ovarian cancer (76.2% and 77.8% vs 52.7%, P =
0.043 and P = 0.043). Positive family history of breast or ovarian cancer (OC)
was more frequently reported among GMB patients with respect to BWT patients
(44.4% vs 13.5%, P = 0.003); GMB, HMB, and BWT patients did not show significant
differences in terms of tumor dissemination pattern, surgical outcomes, platinum
response or survival; neither mutational nor hypermethylation BRCA1 status was
found to be an independent prognostic factor for OC patients. CONCLUSIONS:
Hypermethylation in BRCA1 is associated with earlier occurrence of OC. In
addition, the coexistence of both GBM and HMB is an infrequent event, occurring
in 0.5% of OC cases. Silencing of BRCA1 through mutation and hypermethylation
confers to distinct clinical characteristics of OC patients but similar clinical
outcome with respect to BWT patients.
PMID- 28691939
TI - Autoantibodies Against Glycoprotein 2 Isoforms in Pediatric Patients with
Inflammatory Bowel Disease.
AB - BACKGROUND: Anti-Glycoprotein 2 (GP2) antibodies are associated with a more
complicated course of Crohn's disease (CD) in adults. Four different GP2 isoforms
with different length and antibody-binding sites have been identified so far but
not been explored in serological studies. We aimed to investigate the diagnostic
utility of autoantibodies against all 4 isoforms of GP2 in an exclusively
pediatric population for the first time. METHODS: We included 278 children and
adolescents with inflammatory bowel disease: 164 with CD, 114 with ulcerative
colitis, 83 disease controls (acute gastrointestinal infection, nonspecific
gastrointestinal functional disorders), and 219 healthy controls. Sera were
tested for anti-GP2 antibodies using 4 different isoforms of GP2 for anti
Saccharomyces cerevisiae antibodies, antineutrophil cytoplasmic antibodies, and
pancreatic antibodies. RESULTS: Anti-GP2 antibodies were significantly more
prevalent in patients with CD than in ulcerative colitis and controls. We found a
sensitivity of 38% (with a specificity of 95%) for anti-GP2 IgG against isoform 4
in CD. Anti-GP2 IgA against isoform 1 and anti-GP2 IgG against isoform 4
possessed the best diagnostic values for identification of CD. For the
differentiation of CD from ulcerative colitis anti-GP2 IgG against isoforms 3 and
4 proved to be most accurate markers. Anti-GP2 antibodies were associated with a
more complicated disease behavior and bowel surgery in CD. In a subgroup of
patients with CD, anti-GP2 IgG against isoform 4 proved to be a relatively stable
marker over time independent of disease activity. CONCLUSIONS: Anti-GP2
antibodies against different isoforms are specific markers for CD and for
different phenotypes in pediatric inflammatory bowel disease.
PMID- 28691940
TI - Endoscopic Balloon Dilation Size and Avoidance of Surgery in Stricturing Crohn's
Disease.
AB - BACKGROUND: Endoscopic balloon dilation (EBD) is an effective method for treating
stricture-related obstruction in Crohn's disease. We aimed to identify factors
predictive of successful avoidance of surgery, including endoscopic features, in
patients undergoing balloon dilation. METHODS: We performed a retrospective
review of patients with symptomatic Crohn's disease-related intestinal strictures
undergoing EBD. Clinical, medication use, laboratory, and dilation data,
including the minimum and maximum balloon sizes used, and number of balloons used
per endoscopic session were collected. Multivariate analysis by Cox proportional
hazard regression was used to model future surgical bowel resection. RESULTS: In
a total of 135 subjects undergoing 292 dilations, multivariate modeling
demonstrated that failure to achieve a maximum dilation of 14 mm or more
increased the risk of surgery (hazard ratio [HR] 2.88, 95% confidence limit [CL],
1.10-7.53). Although there was no difference in the risk of future surgery
between maximum EBD sizes of 14 to 15 mm and 16 to 18 mm, those reaching 16 to 18
mm exhibited a longer interval between subsequent dilations (mean 240 +/- 136.7
versus 456 +/- 357.3 d, respectively, P = 0.023). Endoscope passage at index
dilation was not predictive of future surgery (HR 0.63, 95% CL, 0.31-1.26).
Adjusting for covariates of EBD size, stricture location and type, a C-reactive
protein >1.5 mg/dL (HR 2.60, 95% CL, 1.12-5.94), and anti-tumor necrosis factor
initiation after index EBD (HR 2.39, 95% CL, 1.09-5.25) increased the risk of
future surgery. CONCLUSIONS: Although dilation calibers larger than 14 to 15 mm
were not more protective against future surgery, those reaching 16 to 18 mm
underwent maintenance dilation less frequently. The risk of surgery associated
with post-EBD anti-tumor necrosis factor initiation suggests that effective
therapy is often used too late in the disease course.
PMID- 28691941
TI - Extraintestinal Manifestations Are Common in Obese Patients with Crohn's Disease.
AB - INTRODUCTION: Crohn's disease (CD) is a chronic condition associated with the
risk of malabsorption. The incidence of obesity worldwide is increasing, and the
effect of obesity on patients with CD is unknown. We aim to identify traits
related to obesity in a cohort of patients with CD. METHODS: We conducted a
retrospective study of 209 adult patients with CD. Age, Montreal disease
classification, sex, race, duration of disease, erythrocyte sedimentation rate, C
reactive protein levels, physician global assessment, endoscopic appearance,
histologic activity, medication use, and body mass index (BMI) were collected
about each patient. RESULTS: The mean age was 43.4 +/- 14.9 years; 68.9% were
white, and 51.7% were male. The mean duration of disease was 11.0 +/- 10.6 years.
The mean BMI was 26.8 +/- 5.7: underweight 7.7%; normal weight 29.3%; overweight
38.0%; and obese 25%. Patients with higher BMI were more likely to have
extraintestinal manifestations (EIM) (P = 0.005) and more likely to have
nonarthralgia extraintestinal manifestations (P = 0.047). There was a linear
association between proximal CD and decreasing BMI (underweight 31.3%, normal
weight 14.8%, overweight 15.0%, obese 7.7%; P = 0.046). There was no difference
in BMI between patients with and without perianal disease (P = 0.216).
CONCLUSIONS: Most patients were overweight or obese, which correlates with
national population trends. Our data suggest disease location plays a role in
weight modulation in patients with CD. Increased extraintestinal manifestations
in patients with high BMI suggests that the chronic inflammation associated with
obesity may play a role in extraintestinal inflammation.
PMID- 28691942
TI - Rose Bengal Photodynamic Antimicrobial Therapy: A Novel Treatment for Resistant
Fusarium Keratitis.
AB - PURPOSE: To evaluate the efficacy of rose bengal PDAT for the management of a
patient with multidrug-resistant Fusarium keratoplasticum keratitis unresponsive
to standard clinical treatment. METHODS: This case report presents a clinical
case of F. keratoplasticum keratitis not responsive to standard medical care. In
vitro studies from patients culture isolated responded to rose bengal PDAT.
Patient received two treatments with rose bengal 0.1% and exposure to green light
with a total energy of 2.7 J/cm. RESULTS: In vitro results demonstrated the
efficacy of rose bengal PDAT a multidrug-resistant F. keratoplasticum species.
There was complete fungal inhibition in our irradiation zone on the agar plates.
In the clinical case, the patient was successfully treated with 2 sessions of
rose bengal PDAT, and at 8-month follow-up, there was neither recurrence of
infection nor adverse effects to report. CONCLUSIONS: Rose bengal PDAT is a novel
treatment that may be considered in cases of aggressive infectious keratitis.
Further studies are needed to understand the mechanisms of PDAT in vivo.
PMID- 28691943
TI - Effect of a New Matrix Therapy Agent in Persistent Epithelial Defects After
Bacterial Keratitis Treated With Topical Fortified Antibiotics.
AB - PURPOSE: To evaluate the effect of topical application of a matrix regenerating
agent (RGTA) in subjects with a persistent epithelial defect after bacterial
keratitis treated with topical fortified antibiotics. METHODS: In this
prospective case series of 14 subjects (14 eyes) with a persisting corneal ulcer
after the cessation of fortified antibiotics, subjects were treated with an RGTA
at a dose of 1 drop every other day. The main outcome measure was the proportion
of subjects with complete corneal healing 1 month after initiation of treatment.
The secondary outcome measures were the size and depth of corneal ulceration at 1
month, the duration from treatment initiation to complete healing, pain, and
tolerability. The ulceration depth was measured with anterior segment optical
coherence tomography. RESULTS: Complete corneal healing was observed in 11
(78.6%) of the 14 patients after 1 month and in 14 of the 14 (100%) patients
after 3 months. Mean logarithm of the minimum angle of resolution visual acuity
improved from 1.22 +/- 0.59 at inclusion to 0.57 +/- 0.68 at 1 month and to 0.55
+/- 0.68 at 3 months (P < 0.01). Pain according to a visual analog scale
decreased from 0.34 +/- 0.25 to 0.05 +/- 0.09 at 1 month and to 0 at 3 months (P
< 0.001). Amniotic membrane transplantation was not required for any patients.
There were no RGTA-related side effects, and none of the patients reported pain
or discomfort during instillation of the drops. CONCLUSIONS: The RGTA seems to be
efficient for the treatment of a persistent epithelial defect after bacterial
keratitis treated with topical fortified antibiotics.
PMID- 28691944
TI - Efficacy and z* Formula for Minimum Corneal Thickness in Ultraviolet Light Cross
Linking.
PMID- 28691945
TI - Femtosecond Laser-Assisted Tuck-In Penetrating Keratoplasty for Advanced
Keratoglobus With Endothelial Damage.
AB - PURPOSE: To describe the outcomes of femtosecond laser-assisted tuck-in
penetrating keratoplasty as a single-step surgical procedure for visual and
anatomical rehabilitation of patients with severe keratoglobus (KTG) and
endothelial damage. METHODS: Two eyes of a 7-year-old patient with bilateral
severe KTG and previous corneal hydrops were operated. Assisted by the
femtosecond laser, both donor and recipient corneas were prepared. An 8.5-mm full
thickness donor tissue with a peripheral partial-thickness rim of 1.25 mm was
sutured into an 8.5-mm recipient bed with a previously dissected intralamellar
peripheral pocket up to the limbus. The graft was secured with 16 interrupted 10
0 nylon sutures and the peripheral donor rim tucked into the host stromal pocket.
RESULTS: Six months after surgery, both grafts remained healthy and clear. One
eye developed mild postoperative ocular hypertension. No intraoperative or other
postoperative complications were observed. Corrected distance visual acuity was
20/50 in both eyes, with complete functional rehabilitation of the patient.
Restoration of the peripheral corneal thickness was observed in the pachymetric
map. CONCLUSIONS: Femtosecond laser-assisted tuck-in penetrating keratoplasty can
provide excellent anatomical and functional rehabilitation of patients with
severe KTG and endothelial damage, through a single-step surgical procedure and a
single donor cornea per eye. The femtosecond laser permits accurate dissection of
these already thin corneas without inadvertent perforation risk.
PMID- 28691946
TI - Number of Bacteria and Time of Coincubation With Bacteria Required for the
Development of Acanthamoeba Keratitis.
PMID- 28691947
TI - Reply.
PMID- 28691948
TI - Fragrances Categorized According to Relative Human Skin Sensitization Potency.
AB - BACKGROUND: The development of non-animal alternatives for skin sensitization
potency prediction is dependent upon the availability of a sufficient dataset
whose human potency is well characterized. Previously, establishment of basic
categorization criteria for 6 defined potency categories, allowed 131 substances
to be allocated into them entirely on the basis of human information. OBJECTIVES:
To supplement the original dataset with an extended range of fragrance
substances. METHODS: A more fully described version of the original criteria was
used to assess 89 fragrance chemicals, allowing their allocation into one of the
6 potency categories. RESULTS: None of the fragrance substances were assigned to
the most potent group, category 1, whereas 11 were category 2, 22 were category
3, 37 were category 4, and 19 were category 5. Although none were identified as
non-sensitizing, note that substances in category 5 also do not pass the
threshold for regulatory classification. CONCLUSIONS: The combined datasets of
>200 substances placed into potency categories solely on the basis of human data
provides an essential resource for the elaboration and evaluation of predictive
non-animal methods.
PMID- 28691949
TI - Decline in Postmortem Serum Tryptase Levels in Anaphylactic Deaths.
PMID- 28691950
TI - Posttraumatic Stress and Burnout Symptoms in Forensic Doctors and Staff in a
Mortuary.
AB - We aimed to investigate burnout and posttraumatic stress symptoms in mortuary
staff members who work for the Council of Forensic Medicine where more than 4500
autopsies are annually performed.The data were collected from 142 mortuary staff
members from the Council of Forensic Medicine, Turkey. The participants were
divided into the following 4 groups: forensic medicine specialists (n = 40,
28.2%), forensic medicine residents (n = 54, 38.0%), autopsy technicians (n = 24,
16.9%), and other staff members (n = 24, 16.9%). All of the participants
completed a brief sociodemographic form and standardized questionnaires to assess
health symptoms, such as the Maslach Burnout Inventory and Posttraumatic Symptom
Screening Scale.Forensic medicine staff members are at risk for developing
psychological health symptoms, such as burnout or posttraumatic stress, due to
work-related stressors. We observed that autopsy technicians seemed to have more
emotional exhaustion and posttraumatic stress disorder symptoms, whereas resident
doctors had a lower sense of personal accomplishment.
PMID- 28691951
TI - Fatal Self-Poisoning With Massive Propranolol Ingestion in a Young Male
Physician.
AB - Suicidal intoxication from massive propranolol ingestion is rare. Surprisingly,
no reported cases have involved physicians. The author herein reports a case of
self-poisoning death due to ingestion of propranolol by a young male physician. A
31-year-old man with major depressive disorder was found dead in his dormitory
room. Fifteen empty packages, each having contained ten 40-mg propranolol
tablets, were found without any tablets leftover in his room. A suicide note was
also found in his room. He was thus alleged to have ingested 6 g of propranolol
for self-poisoning. Autopsy findings revealed approximately 150 mL of pink fluid
with some partially dissolved pink tablets in the stomach. No anatomic cause of
death was found, except for mild dilatation of cerebral ventricles. Toxicologic
analysis revealed propranolol in his blood and gastric contents. The cause of
death was attributed to acute cardiac arrest due to severe acute propranolol
intoxication from self-poisoning caused by major depressive disorder possibly
secondary to organic brain syndrome.
PMID- 28691952
TI - Intrapatient Variability in the Pharmacokinetics of Etanercept Maintenance
Treatment.
AB - AIM: Etanercept has shown to mediate a favorable effect on immune-mediated
inflammatory diseases (IMID), including plaque psoriasis. Therapeutic drug
monitoring (TDM) of etanercept could improve clinical outcome and cost
effectiveness. A high intrapatient variability (IPV) of etanercept trough
concentrations at standard dosing would reduce the feasibility of therapeutic
drug monitoring. Studies have focused on the interpatient differences associated
with the exposure to biologics. The aim of this study was to determine IPV of
etanercept and correlate etanercept trough concentrations and IPV with treatment
response. METHODS: Repetitive serum samples of 29 psoriasis patients on standard
etanercept maintenance treatment were collected. In these samples, etanercept
trough concentrations were determined and IPV was assessed in relation to
response to treatment. RESULTS: The median IPV of etanercept trough
concentrations was 33.7% (Q1 = 21.3% and Q3 = 51.7%) ranging from 8% to 155%. All
6 nonresponders showed an IPV at or above the median value of 33.7%. The 6
nonresponders showed a higher IPV as compared to the 23 responders (53.9% versus
24.2%; P = 0.031). The mean etanercept trough concentration for each patient
ranged from 0.7 to 6.8 mcg/mL, with a median trough concentration of 2.7 mcg/mL.
Patients with an IPV above the median had lower mean etanercept trough
concentrations compared to patients with an IPV below the median (1.96 mcg/mL,
95% CI, 1.7-2.4 versus 3.2 mcg/mL, 95% CI, 2.7-4.0; P = 0.001). CONCLUSIONS: The
median IPV of etanercept trough concentrations in this study population was
33.7%. A higher IPV was correlated with lower etanercept trough concentrations
and with nonresponsiveness. Prospective trials are required to demonstrate the
value of adjusting the etanercept dose based on drug trough concentrations. The
relatively high IPV observed in this study may complicate therapeutic drug
monitoring.
PMID- 28691954
TI - Maintenance Belatacept-Based Immunosuppression in Lung Transplantation Recipients
Who Failed Calcineurin Inhibitors.
AB - BACKGROUND: Traditional immunosuppressive regimens (ISR) used in lung
transplantation rely on calcineurin inhibitors (CNI) that occasionally cause
severe adverse reactions necessitating discontinuation. Belatacept is a novel
costimulation antagonist approved for use in renal transplantation which lacks
data in lung transplantation. This series aims to describe the response to
belatacept ISR in 11 lung transplantation recipients after CNI failure. METHODS:
Single-center, retrospective medical record review of adult lung transplant
recipients (LTR) before and after conversion to belatacept-based ISR. Patients
were evaluated at fixed time points before and after belatacept initiation.
Primary outcome was incidence of acute cellular rejection (ACR). Secondary
outcomes included incidence of infection, chronic lung allograft dysfunction
(CLAD) progression, death, change in mean arterial pressure, and estimated
glomerular filtration rate. RESULTS: Eleven LTRs received belatacept with a mean
of 246 (91-1064) days of follow-up after conversion. Four were changed to
belatacept for thrombotic thrombocytopenic purpura, 3 for posterior reversible
encephalopathy syndrome, 2 for recurrent ACR, 1 for CLAD, and 1 for renal
sparing. ACR was not different before and after belatacept (P = 0.17). Mean
estimated glomerular filtration rate was significantly higher postbelatacept
(32.53 vs 45.26, P = 0.04). Mean incidence of infections (24.4% vs 16.0%, P =
0.55) and mean arterial pressure (97.5 vs 92.1 P = 0.38) were not different.
Progression of CLAD occurred in 2 patients. At the end of follow-up, 7 of 11
patients were alive. CONCLUSIONS: Belatacept-based ISR appear to produce
reasonable results in LTRs who fail CNI-based ISR. Larger prospective trials
appear warranted in lung transplantation.
PMID- 28691955
TI - Children with Obsessive-Compulsive Symptomology in the General Population:
Different Subtypes?
AB - OBJECTIVE: Obsessive-compulsive disorder (OCD) is a moderately prevalent
neurodevelopmental disorder, and many children suffer from subclinical obsessive
compulsive (OC) symptoms. The disorder is heterogeneous and has high comorbidity
rates. In early disease stages of psychiatric disorders, symptoms are typically
hard to attribute exclusively to specific disorders. The authors investigated
whether profiles of neuropsychiatric symptoms can be distinguished within a large
population-based study of school-aged children (7-10 years) scoring high on OC
symptoms. METHODS: OC symptoms and comorbid symptoms common in pediatric OCD were
assessed: symptoms of attention-deficit hyperactivity disorder, oppositional
defiant disorder, autism, and anxiety. Latent profile analysis was performed on
the subgroup of children scoring high on OC symptoms (high-OC sample, n = 209,
i.e., 4.5% of total sample, n = 4632) using the z scores of the measures of
comorbid symptoms as indicators. RESULTS: Three distinguishable profiles were
found within the high-OC sample. The first subgroup ("OC-specific"; 81.3%, 3.7%
of total sample) had only OC-specific problems, the second subgroup ("Comorbid
OC"; 11.0%, 0.5% of total sample) had high scores on all measures of comorbid
symptomology, and the third subgroup ("Autistic OC"; 7.7%, 0.3%, of total sample)
scored especially high on autism. CONCLUSION: The findings show that profiles
based on neuropsychiatric symptoms can be distinguished within a population-based
sample of school-aged children scoring high on obsessive-compulsive symptoms.
These profiles may be useful in establishing patterns of symptom course during
development. Longitudinal follow-up is necessary to ascertain whether at a later
age these subgroups still differ in their symptom profile and neuropsychiatric
trajectory.
PMID- 28691957
TI - Empirically Identified Subgroups of Children Served in Part C Early Intervention
Programs.
AB - OBJECTIVE: Early intervention (EI) programs under Part C of the Individuals with
Disabilities Education Act serve a developmentally heterogeneous population of
infants and toddlers with or at risk of developmental delays or disabilities. The
aim of this study was to identify empirically distinct subgroups of children in
EI so as to inform early prognosis and service planning. METHODS: We applied
mixture modeling to developmental assessment data from 1513 children who enrolled
in a large, urban EI program between 2009 and 2013. The observed variables were
children's EI-entry developmental quotients (DQs) in 5 domains (communication,
cognitive, motor, adaptive, and personal-social) as assessed by the Battelle
Developmental Inventory, Second Edition. RESULTS: A 4-class model showed the best
fit to the data, revealing subgroups with distinct developmental profiles.
Children in the first subgroup showed a severe delay in communication with less
severe delays in the other domains. Children in the second subgroup likewise
showed a severe delay in communication, but with comparably severe delays in the
cognitive and motor domains. Profiles for the third and fourth subgroups showed
the same overall patterns as those for the first and second subgroups,
respectively, but to a less severe degree. Developmental trajectories differed by
subgroup. CONCLUSION: Consideration of subgroups based on children's
developmental assessment scores provides insight into underlying commonalities
among children with different presenting diagnoses on entry into EI. The
subgroups also have clinical relevance in terms of both practitioners' and
parents' understanding of children's likely service needs and developmental
trajectories.
PMID- 28691958
TI - Guidelines for the Provision and Assessment of Nutrition Support Therapy in the
Pediatric Critically Ill Patient: Society of Critical Care Medicine and American
Society for Parenteral and Enteral Nutrition.
AB - This document represents the first collaboration between two organizations,
American Society of Parenteral and Enteral Nutrition and the Society of Critical
Care Medicine, to describe best practices in nutrition therapy in critically ill
children. The target of these guidelines is intended to be the pediatric (> 1 mo
and < 18 yr) critically ill patient expected to require a length of stay greater
than 2 or 3 days in a PICU admitting medical, surgical, and cardiac patients. In
total, 2,032 citations were scanned for relevance. The PubMed/Medline search
resulted in 960 citations for clinical trials and 925 citations for cohort
studies. The EMBASE search for clinical trials culled 1,661 citations. In total,
the search for clinical trials yielded 1,107 citations, whereas the cohort search
yielded 925. After careful review, 16 randomized controlled trials and 37 cohort
studies appeared to answer one of the eight preidentified question groups for
this guideline. We used the Grading of Recommendations, Assessment, Development
and Evaluation criteria to adjust the evidence grade based on assessment of the
quality of study design and execution. These guidelines are not intended for
neonates or adult patients. The guidelines reiterate the importance of
nutritional assessment, particularly the detection of malnourished patients who
are most vulnerable and therefore potentially may benefit from timely
intervention. There is a need for renewed focus on accurate estimation of energy
needs and attention to optimizing protein intake. Indirect calorimetry, where
feasible, and cautious use of estimating equations and increased surveillance for
unintended caloric underfeeding and overfeeding are recommended. Optimal protein
intake and its correlation with clinical outcomes are areas of great interest.
The optimal route and timing of nutrient delivery is an area of intense debate
and investigations. Enteral nutrition remains the preferred route for nutrient
delivery. Several strategies to optimize enteral nutrition during critical
illness have emerged. The role of supplemental parenteral nutrition has been
highlighted, and a delayed approach appears to be beneficial. Immunonutrition
cannot be currently recommended. Overall, the pediatric critical care population
is heterogeneous, and a nuanced approach to individualizing nutrition support
with the aim of improving clinical outcomes is necessary.
PMID- 28691959
TI - Neuroimaging in Sepsis: Panacea or Pandora's Box?
PMID- 28691960
TI - Fluid Management After Congenital Cardiac Surgery: The Good, the Bad, and the
Indifferent.
PMID- 28691961
TI - A Tale of Two Controversies: Low Cardiac Output Syndrome and Corticosteroids.
PMID- 28691962
TI - Does a Spoonful of Insulin Make the Acute Kidney Injury Go Down?
PMID- 28691963
TI - Do Subspecialty Patients Need Special Evaluation to Screen for Deterioration?
PMID- 28691964
TI - Can a Risk Assessment Tool Get Everyone on the Same Page?
PMID- 28691965
TI - Burnout in the ICU-What Do We Do Now?
PMID- 28691966
TI - Pediatric Poisonings: Do They Really Need That PICU Bed?
PMID- 28691967
TI - Precision Medicine in Critical Care Requires an Understanding of Pharmacokinetic
Variability.
PMID- 28691968
TI - Science and Acute Kidney Injury: Exploring the Rhetoric of Standardization.
PMID- 28691969
TI - The authors reply.
PMID- 28691970
TI - Pediatric Multiple Organ Dysfunction Syndrome Promising Therapies: What About
Vitamin D Supplementation?
PMID- 28691971
TI - The authors reply.
PMID- 28691972
TI - Changing the Patient Safety Paradigm.
PMID- 28691973
TI - A SWIFT Method for Handing Off Obstetrical Patients on the Labor Floor.
AB - OBJECTIVE: The aim of this study was to improve patient handoffs on the labor
floor. METHODS: A prospective cohort study of obstetrics residents at Montefiore
Medical Center was performed between 2012 and 2014. Labor-floor handoffs were
recorded before and after didactic sessions as well as after installation of
whiteboards formatted with the mnemonic SWIFT (Subject, Why?, Issues, Fetus,
Tasks). Handoff transcripts were evaluated by obstetricians blinded to timing and
speaker identity. An intraclass correlation coefficient accounted for evaluator
differences. Data analysis was by ordinal logistic regression, the generalized
estimating equations method (correlated data), and Bonferroni adjustment
(multiple comparisons). RESULTS: Forty-five handoffs were evaluated (15 each
predidactics, postdidactics, and postwhiteboard revision). Higher completeness
scores over time were noted for admission reason, labor concerns, and task list
(not statistically significant). Comprehensive score increases prelecture to
postwhiteboard were seen in handoff clarity (2.81 versus 2.91) and overall
quality (2.77 versus 2.81) (not statistically significant). A subanalysis of four
residents who gave multiple handoffs over different periods revealed few
significant changes over time. Greater interevaluator consistency was noted with
more objective elements. CONCLUSIONS: The mnemonic SWIFT, with formalized
curricula for obstetrical resident training focusing on new learners and
increased faculty involvement and reinforcement, may result in improvement of
handoffs on the labor floor.
PMID- 28691974
TI - Peroral Endoscopic Myotomy in Children With Achalasia: A Relatively Long-term
Single-center Study.
AB - BACKGROUND: Achalasia is a disease caused by neuromuscular dysfunction in the
esophagogastric junction, with a relatively low incidence among children. Peroral
endoscopic myotomy (POEM) is a new endoscopic procedure for the treatment of
achalasia; however, it is rarely applied in children. OBJECTIVES: We aim to study
the feasibility, safety, and effectiveness of POEM as a treatment for pediatric
achalasia. METHODS: A total of 21 pediatric patients (ages from 11 months to 18
years) diagnosed as having achalasia and treated with POEM from October of 2014
to October of 2016 in our hospital were included in our study. Indices such as
clinical manifestations, nutritional status, Eckardt scores, high-resolution
esophageal manometric measurements, gastroduodenoscopic findings, and upper
gastroenterographic findings after treatment were respectively compared with
those before treatment to analyze the effectiveness and safety of POEM. RESULTS:
All of the 21 children successfully received POEM. The patients were followed up
for duration ranged from 3 to 24 months. Among these children, symptoms such as
vomiting and dysphagia were significantly alleviated or resolved. The Eckardt
scores had an average drop of 7 points after treatment compared with those before
treatment. Postoperative gastroduodenoscopy and upper gastroenterography showed
that the opening of the cardiac orifice was significantly enlarged and
obstruction at the lower esophagus was significantly relieved. CONCLUSIONS: POEM
is a mini-invasive technique and a promising new treatment for pediatric
patients, making it worthy of further clinical research and application.
PMID- 28691975
TI - Stability of Cortisol and Cortisone in Human Breast Milk During Holder
Pasteurization.
AB - Human donor milk is the feeding of choice for preterm infants, when own mother's
milk is not available. Holder pasteurization is necessary to secure the safety of
donor milk, although it can affect milk quality by reduction of nutritional and
bioactive components. Recently, research has focused on the potential role of
breast milk glucocorticoids for infant development. At this moment, it is unknown
whether pasteurization affects milk glucocorticoid levels. Therefore, we assessed
whether Holder pasteurization, the most frequently used method nowadays, reduces
breast milk cortisol and cortisone levels, using breast milk samples from 30
women who delivered at term. We found tight correlations between pre- and
postpasteurization levels of cortisol (R = 0.99) and cortisone (R = 0.98), and
good agreement in Passing and Bablok regression analysis. In conclusion, cortisol
and cortisone in human term breast milk are not significantly affected by Holder
pasteurization.
PMID- 28691976
TI - Distinct Lipoprotein Curves in Normal Weight, Overweight, and Obese Children and
Adolescents.
AB - OBJECTIVES: Pediatric lipoprotein curves are based on population-based samples.
As obesity, may alter lipoprotein levels, cutoffs not adjusted for body mass
index (BMI) are potentially inappropriate. We aimed to develop distinct serum
lipid curves based on sex- and BMI-percentiles for children and adolescents.
METHODS: Cross-sectional analysis included all healthy children and adolescents
(age range 2-17 years) with available serum lipid concentrations (n = 152,820 of
approximately 1.2 million children and adolescents per study year). These
children and adolescents were categorized according to sex- and age-stratified
BMI-percentiles: 100,375 normal weight (5th-85th percentile), 26,028 overweight
(85th-95th percentile) and 26,417 obese (>=95th percentile) individuals. Excluded
were individuals with hyperlipidemia, gastrointestinal disease, thyroid disease
and lipid-lowering medications. Lambda-Mu-Sigma, smoothed percentile lipid curves
were computed. RESULTS: Obese children had a lipid profile pattern throughout
childhood and adolescence similar to that of normal weight subjects but with a
significant upward shift in total cholesterol (TC), low-density lipoprotein
cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), and
triglycerides (TGs) and a downward shift in high-density lipoprotein-cholesterol
(HDL-C). Obese boys had 13 mg/dL higher TC levels (P < 0.001), 11 mg/dL higher
LDL-C levels, 15 mg/dL higher non-HDL-C levels, and 5 mg/dL lower HDL-C levels (P
< 0.001). Obese girls had 6 mg/dL higher TC levels, 7 mg/dL higher LDL-C levels,
11 mg/dl higher non-HDL-C levels, and 6 mg/dL lower HDL-C levels (P < 0.001).
CONCLUSIONS: Across a large, nationally representative cohort of children and
adolescents, lipoprotein levels were found to vary in relation to weight status.
On the basis of these findings, it is suggested that when evaluating the lipid
profile in the pediatric population, in addition to sex-based curves, clinical
decision making may require consideration of BMI-stratified curves.
PMID- 28691978
TI - Occam's Razor Could Not Cut It: Tale of 2 Headaches in a Postpartum Patient: A
Case Report.
AB - Not all postpartum headaches are caused by dural puncture, and it is possible for
postpartum patients to have >1 cause for headache. After neuraxial block with an
incidental large-gauge dural puncture, our patient developed a severe, classic
postdural puncture headache which initially responded to an epidural blood patch.
The patient was readmitted 2 days after discharge complaining of recurrent
headache less characteristic of a postdural puncture headache, now being
bifrontal/retro-orbital and without clear positional component. Computerized
tomography and magnetic resonance imaging revealed an enlarged pituitary gland
with a possible hemorrhagic focus; all endocrine parameters were normal. The
patient was ultimately diagnosed with lymphocytic adenohypophysitis, an
autoimmune inflammation of the anterior pituitary gland.
PMID- 28691979
TI - Perioperative Management for Abdominal Surgery in Bilateral Diaphragmatic
Paralysis: A Case Report and Literature Review.
AB - The optimal approach to postoperative analgesia in patients with bilateral
diaphragmatic paralysis undergoing abdominal surgery remains unclear. We report a
69-year-old woman with bilateral diaphragmatic paralysis who underwent a
laparoscopic hernia repair and an open laparotomy for reversal of a Hartmann
procedure under general anesthesia. Postoperative analgesia was provided by
intravenous opioid and epidural local anesthetic and opioid, respectively. The
patient's trachea was successfully extubated at the end of both surgical
procedures. Epidural analgesia was associated with better pain control and
shorter intensive care unit stay.
PMID- 28691980
TI - Sudden Increase in EtCO2 During Upper Endoscopy Under General Endotracheal
Anesthesia Suggests the Presence of Tracheoesophageal Fistula: A Case Report.
AB - Acquired tracheoesophageal fistula is a rare and devastating complication of lung
cancer. The diagnosis is typically confirmed on barium esophagram. We report a
case of a patient with lung cancer status after palliative chemoradiotherapy and
esophageal stenting for malignant stenosis who presented with signs and symptoms
suggestive of tracheoesophageal fistula; however, no evidence of fistula was
found on barium esophagram. During subsequent esophagogastroduodenoscopy, the
presence of a fistula was verified by capnography, given extreme elevations in
end-tidal CO2 concentrations during endoscopic CO2 insufflation.
PMID- 28691981
TI - Use of 23.4% Saline in Symptomatic Vasospasm and Cushing's Triad to Prevent
Herniation and Death: A Case Report.
AB - A 53-year-old woman with migraines presented with Hunt-Hess grade 5 and Fisher
grade 4 subarachnoid hemorrhage with intraventricular hemorrhage. She experienced
severe vasospasm requiring intra-arterial medications. Continued vasospasm and
edema resulted in Cushing's triad with profound tachypnea. Three percentage
saline was administered twice without improvement. Despite the general practice
to wait until complete neurologic deterioration before administering 23.4%
saline, it was administered on 2 separate occasions, once after the failure of
the 2 boluses of 3% saline and once on the reappearance of Cushing's triad 24
hours later, and on each occasion produced overall clinical improvement. The
patient was subsequently discharged to a rehabilitation facility and then home. A
paradigm shift to earlier intervention with 23.4% saline may improve overall
outcomes in patients with severe intracranial hypertension refractory to 3%
saline and impending herniation.
PMID- 28691982
TI - Percutaneous Valve in Valve Implantation for Dysfunctional Bioprosthetic Valves:
A Case Report.
AB - Percutaneous valve-in-valve therapy is a life-saving procedure for patients at
high risk of reoperation due to dysfunctional bioprosthetic valves. We have
reviewed 3 typical cases of a valve-in-valve procedure using high-quality images
to demonstrate the suitability of this method for aortic, mitral, and tricuspid
positions. Three-dimensional transesophageal echocardiography combined with other
modalities such as computerized tomography and fluoroscopy are key elements for
anesthesia and procedural guidance, especially as immediate tools to assess
valvular function and specific procedure-related complications.
PMID- 28691983
TI - Incorrect Diagnosis of Type A Aortic Dissection Attributed to Motion Artifact
During Computed Tomographic Angiography: A Case Report.
AB - Early diagnosis of aortic dissection is important to reduce mortality, with
surgical management representing standard treatment. Current methods of
diagnosing type A aortic dissection include computed tomography angiography
(CTA), magnetic resonance imaging, catheter-based arteriography, and
transesophageal echocardiography. While each method has merits, there exists
potential for false-positive findings. We present a case of a patient who was
diagnosed with type A aortic dissection by CTA, but was found to not have an
aortic dissection by transesophageal echocardiography under general anesthesia,
preventing an unnecessary sternotomy. The echocardiographic findings suggested
CTA artifact.
PMID- 28691984
TI - Stepwise Rostrocaudal Brainstem Anesthesia as a Complication of Local Anesthesia:
A Case Report.
AB - Iatrogenic cranial nerve palsies can rarely complicate neurosurgical, oral
maxillofacial, and otolaryngological procedures. Among the most serious
complications of cranial nerve palsy is upper airway obstruction, which is life
threatening. We present a case of multiple cranial nerve palsies evolving rapidly
in a rostrocaudal stepwise fashion after infiltration of lidocaine to repair a
cerebrospinal fluid leak in a patient postoccipital craniectomy. This led to
hypoxic respiratory failure requiring mechanical ventilation before resolving
spontaneously. This is the first known case of accidental brainstem anesthesia
secondary to lidocaine infiltration at an occipital craniectomy site and serves
to caution clinicians who manage similar patients.
PMID- 28691985
TI - Hemodynamically Directed Two-Person Chest Compressions: A Case Report.
AB - Cardiopulmonary resuscitation has a low success rate both in and out of the
hospital setting. Return of spontaneous circulation, however, is considerably
higher for intraoperative cardiac arrests. Chest compressions remain of utmost
importance. Optimal chest compression depth is believed to be greater than 5 cm.
However, this depth is often not achieved. We describe a case in which the
adequacy of chest compressions, based on hemodynamic monitoring, was achieved
with 2 persons simultaneously providing a compressive force. This hemodynamic
directed care resulted in return of spontaneous circulation on 2 separate
occasions.
PMID- 28691986
TI - The Role of Sugammadex in Symptomatic Transient Neonatal Myasthenia Gravis: A
Case Report.
AB - We describe the case of a 3-week-old boy with pyloric stenosis who presented for
laparoscopic pyloromyotomy in the setting of symptomatic transient neonatal
myasthenia gravis. The patient received muscle relaxation with rocuronium, and
neuromuscular blockade was successfully reversed with sugammadex with recovery
guided by train-of-four monitoring. He was extubated uneventfully without
complications. Because sugammadex binds directly to rocuronium rather than
interfering with acetylcholine metabolism, it might provide a good option for
reversal of neuromuscular blockade in transient neonatal myasthenia gravis.
PMID- 28691987
TI - Multiple Targetoid Plaques.
PMID- 28691988
TI - Re: "Use of Cyanoacrylate Glue Casting for Stabilization of Periocular Skin
Grafts and Flaps".
PMID- 28691989
TI - Reply re: "Use of Cyanoacrylate Glue Casting for Stabilization of Periocular Skin
Grafts and Flaps".
PMID- 28691990
TI - Re: "Evaluation of the Microvascular Blood Flow, Oxygenation, and Survival of
Tarsoconjunctival Flaps Following the Modified Hughes Procedure".
PMID- 28691991
TI - Intraoperative Mitomycin C in the Treatment of Recalcitrant Ankyloblepharon.
PMID- 28691992
TI - Closure of the Lateral Canthotomy.
PMID- 28691993
TI - Novel Approach to Skin Closure Following Upper Eyelid Blepharoplasty.
PMID- 28691994
TI - Core Outcome Domains for Clinical Trials on Somatic Symptom Disorder, Bodily
Distress Disorder, and Functional Somatic Syndromes: European Network on Somatic
Symptom Disorders Recommendations.
AB - OBJECTIVE: The harmonization of core outcome domains in clinical trials
facilitates comparison and pooling of data, and simplifies the preparation and
review of research projects and comparison of risks and benefits of treatments.
Therefore, we provide recommendations for the core outcome domains that should be
considered in clinical trials on the efficacy and effectiveness of interventions
for somatic symptom disorder, bodily distress disorder, and functional somatic
syndromes. METHODS: The European Network on Somatic Symptom Disorders group of
more than 20 experts in the field met twice in Hamburg to discuss issues of
assessment and intervention research in somatic symptom disorder, bodily distress
disorder, and functional somatic syndromes. The consensus meetings identified
core outcome domains that should be considered in clinical trials evaluating
treatments for somatic symptom disorder and associated functional somatic
syndromes. RESULTS: The following core domains should be considered when defining
ascertainment methods in clinical trials: a) classification of somatic symptom
disorder/bodily distress disorder, associated functional somatic syndromes, and
comorbid mental disorders (using structured clinical interviews), duration of
symptoms, medical morbidity, and prior treatments; b) location, intensity, and
interference of somatic symptoms; c) associated psychobehavioral features and
biological markers; d) illness consequences (quality of life, disability, health
care utilization, health care costs; e) global improvement and treatment
satisfaction; and f) unwanted negative effects. CONCLUSIONS: The proposed
criteria are intended to improve synergies of clinical trials and to facilitate
decision making when comparing different treatment approaches. These
recommendations should not result in inflexible guidelines, but increase
consistency across investigations in this field.
PMID- 28691995
TI - The Role of Psychological Stress on Heart Autophagy in Mice With Heart Failure.
AB - OBJECTIVE: Psychological stress in chronic heart failure (CHF) is associated with
systemic neurohormonal and immune system responses and increased mortality.
Autophagy refers to the biological process of degradation and recycling of
dysfunctional cellular components. We investigated the role of psychological
stress on autophagy function in CHF mice. METHODS: C57BL/6 mice underwent
transverse aortic constriction, with or without combined acoustic and restraint
stress, and cardiac function was assessed by echocardiography analysis. Serum
corticosterone and angiotensin II (Ang II) were determined using enzyme-linked
immunosorbent assay (ELISA). Autophagy and oxidative stress were measured with
immunohistochemistry and quantitative polymerase chain reaction, and chloroquine
and rapamycin were used to detect autophagy flux. In vivo, cardiomyocytes were
cultured with or without Ang II or N-acetylcysteine, and autophagy and oxidative
stress were also detected. RESULTS: A 1-week stress exposure significantly
increased serum levels of corticosterone and Ang II (p = .000), increased levels
of oxidative stress, induced overt heart failure, and increased mortality (p =
.002). Furthermore, stress exposure unregulated messenger RNA expression of Bcl-2
interacting coiled-coil protein 1 (10.891 [3.029] versus 4.754 [1.713], p =
.001), cysteine-rich domain containing beclin-1 interacting (6.403 [1.813] versus
3.653 [0.441], p = .006), and autophagy 7 (111.696 [4.049] versus 6.189 [1.931],
p = .017), increased expression of autophagosomal, and decreased clearance of
autophagosomes. In vitro, Ang II significantly increased autophagy flux in
cultured cardiomyocytes, which could be partly inhibited by N-acetylcysteine.
CONCLUSIONS: Psychological stress may contribute to the development of CHF by
enhancing heart oxidative stress and impairing autophagy flux.
PMID- 28691997
TI - The Clinical Significance of Posterior Insular Volume in Adolescent Anorexia
Nervosa.
AB - OBJECTIVE: The diagnostic criterion disturbance in the experience of the body
remains a poorly understood and persistent feature of anorexia nervosa (AN).
Increased sophistication in understanding the structure of the insular cortex-a
neural structure that receives and integrates visceral sensations with action and
meaning-may elucidate the nature of this disturbance. We explored age, weight
status, illness severity, and self-reported body dissatisfaction associations
with insular cortex volume. METHODS: Structural magnetic resonance imaging data
were collected from 21 adolescents with a history of AN and 20 age-, sex-, and
body mass index-matched controls. Insular cortical volumes (bilateral anterior
and posterior regions) were identified using manual tracing. RESULTS: Volumes of
the right posterior insula demonstrated the following: (a) a significant age by
clinical status interaction (beta = -0.018 [0.008]; t = 2.32, p = .02) and (b)
larger volumes were associated with longer duration of illness (r = 0.48, p <
.04). In contrast, smaller volumes of the right anterior insula were associated
with longer duration of illness (r = -0.50, p < .03). The associations of insular
volume with body dissatisfaction were of moderate effect size and also of
opposite direction, but a statistical trend in right posterior (r = 0.40, p < .10
in right posterior; r = -0.49, p < .04 in right anterior). CONCLUSIONS: In this
exploratory study, findings of atypical structure of the right posterior insular
cortex point to the importance of future work investigating the role of visceral
afferent signaling in understanding disturbance in body experience in AN.
PMID- 28691998
TI - Employer and Promoter Perspectives on the Quality of Health Promotion Within the
Healthy Workplace Accreditation.
AB - OBJECTIVES: To explore the employers' and promoters' perspective of health
promotion quality according to the healthy workplace accreditation. METHODS: We
assessed the perspectives of 85 employers and 81 health promoters regarding the
quality of health promotion at their workplaces. The method of measurement
referenced the European Network for Workplace Health Promotion (ENWHP) quality
criteria. RESULTS: In the large workplaces, the accredited corporation employers
had a higher impression (P < 0.001) of all criteria. The small-medium accredited
workplace employers had a slightly higher perspective than non-accredited ones.
Nevertheless, there were no differences between the perspectives of health
promoters from different sized workplaces with or without accreditation (P >
0.05). CONCLUSIONS: It seems that employers' perspectives of healthy workplace
accreditation surpassed employers from non-accredited workplaces. Specifically,
large accredited corporations could share their successful experiences to
encourage a more involved workplace in small-medium workplaces.
PMID- 28691999
TI - Mortality of Talc Miners and Millers From Val Chisone, Northern Italy: An Updated
Cohort Study.
AB - OBJECTIVE: The aim of this study was to update the analysis of mortality of a
cohort of talc miners and millers in Northern Italy. METHODS: We analyzed the
mortality during 1946 to 2013 of 1722 male workers in an asbestos-free talc mine
(1166 miners and 556 millers) employed during 1946 to 1995. RESULTS: The overall
standardized mortality ratio (SMR) was 1.24 [95% confidence interval (95% CI)
1.17 to 1.32]; no deaths were observed from pleural cancer; mortality from lung
cancer was not increased. Mortality from pneumoconiosis was increased (SMR 26.62;
95% CI 20.71 to 33.69), in particular among miners, and was associated with
duration of employment and time since first employment. CONCLUSIONS: We confirmed
the lack of association between exposure to asbestos-free talc, lung cancer, and
mesothelioma. Increased mortality from pneumoconiosis among miners is
attributable to past exposure to silica.
PMID- 28692000
TI - The Role of Psychological Stress Reactions in the Longitudinal Relation Between
Workplace Bullying and Turnover.
AB - OBJECTIVES: To investigate the association between workplace bullying and change
of job/unemployment, and to investigate whether psychological stress reactions
constitute a potential pathway linking workplace bullying and change of
job/unemployment. METHODS: We used questionnaire data on workplace bullying and
psychological stress reactions and register data on change of job/unemployment.
We applied a multiple pathway approach to estimate the proportion of the
association between workplace bullying and subsequent change of job/unemployment
that was potentially mediated by psychological stress reactions. RESULTS:
Workplace bullying was associated with risk of change of job (odds ratio [OR] =
1.35; 95% confidence interval [CI]: 1.06-1.72; 24% potentially mediated by
psychological stress reactions) and unemployment (OR = 4.90; 95% CI: 3.18-7.55;
19% potentially mediated by psychological stress reactions). CONCLUSION:
Workplace bullying has important consequences for labor market outcomes.
Psychological stress reactions may play a vital role in this process.
PMID- 28692001
TI - Prevalence and Perception of Risky Health Behaviors Among Construction Workers.
AB - OBJECTIVE: This study aimed to evaluate construction workers' health behaviors,
attitudes, and perceptions of health risks from work related and non-work related
hazards. METHODS: Construction workers completed a survey that assessed hazardous
health behaviors (such as alcohol and tobacco use), attitudes toward health, and
health risk perceptions. We compared construction workers' health behaviors to
general population data from the behavioral risk factor surveillance system
(BRFSS). RESULTS: Construction workers reported greater smoking and drinking
compared with their age-adjusted white man counterparts in Missouri. While there
was a high awareness of work-related health and safety risks, concerns about
general health risks did not correspond with risks from relevant health
behaviors. CONCLUSION: Educational efforts have created awareness of work-related
safety and health issues in this population; similar efforts are needed to
address disparities of general health behaviors.
PMID- 28692002
TI - Impact of Work Task-Related Acute Occupational Smoke Exposures on Select
Proinflammatory Immune Parameters in Wildland Firefighters.
AB - OBJECTIVE: A repeated measures study was used to assess the effect of work tasks
on select proinflammatory biomarkers in firefighters working at prescribed burns.
METHODS: Ten firefighters and two volunteers were monitored for particulate
matter and carbon monoxide on workdays, January to July 2015. Before and after
workshift dried blood spots were analyzed for inflammatory mediators using the
Meso Scale Discovery assay, while blood smears were used to assess leukocyte
parameters. RESULTS: Firefighters lighting with drip-torches had higher cross
work-shift increases in interleukin-8, C-reactive protein, and serum amyloid A
compared with holding, a task involving management of fire boundaries. A positive
association between interleukin-8 and segmented-neutrophil was observed.
CONCLUSION: Results from this study suggest that intermittent occupational diesel
exposures contribute to cross-work-shift changes in host systemic innate
inflammation as indicated by elevated interleukin-8 levels and peripheral blood
segmented-neutrophils.
PMID- 28692003
TI - Comparison of Psychological, Quality of Life, Work-Limitation, and Socioeconomic
Status Between Patients With Occupational Asthma and Work-Exacerbated Asthma.
AB - OBJECTIVE: The aim of this study was to compare psychological status, quality of
life (QoL), work limitation, and socioeconomic status between patients with
occupational asthma (OA) and work-exacerbated asthma (WEA). METHODS: The
following questionnaires were administered to participants: Beck anxiety and
depression (II) inventories, Marks' Asthma Quality of Life Questionnaire, and
Work Limitations Questionnaire. Cross-sectional analyses between OA and WEA
subgroups were completed. RESULTS: There were 77 participants. WEA subjects had a
trend to higher anxiety scores (OA = 9.2 +/- 8.0, WEA = 12.8 +/- 8.3, P = 0.07,
Cohen d = 0.4). Depression scores trended higher for those with WEA (OA = 9.6 +/-
10.3, WEA = 13.4 +/- 13.5, P = 0.2, Cohen d = 0.3). QoL was comparable between
groups. WEA subjects had fewer work limitations (N = 50, OA = 25.1 +/- 27.3, WEA
= 20.6 +/- 24.4, P = 0.56, Cohen d = 0.3) and OA subjects were more likely to
have reduced income. CONCLUSION: In a tertiary clinic, there were some modest
differences for specific variables between OA and WEA subjects that may help
inform management.
PMID- 28692007
TI - Can an Internal Locus of Control and Social Support Reduce Work-Related Levels of
Stress and Strain?: A Comparative Study Between Spanish Owners and Managers.
AB - OBJECTIVE: The aim of this article is to assess the role played by both
individual and contextual factors in reducing the manager's levels of stress and
strain within the workplace setting. This article also highlights the manager's
locus of control (LOC) as an internal factor and emphasizes the social support
variable as a contextual factor. METHODS: We use a sample of 332 respondents
belonging to Spanish manufacturing and services firms and a structural equation
modeling technique (partial least squares path modeling). RESULTS: The results
reveal that there are significant differences between managers and owners about
stress-strain relationship. CONCLUSIONS: The study provides support for the
literature on stress management, which emphasizes the importance of a LOC and
social support in influencing stress and strain between managers and owners.
PMID- 28692006
TI - Brain signature and functional impact of centralized pain: a multidisciplinary
approach to the study of chronic pelvic pain (MAPP) network study.
AB - Chronic pain is often measured with a severity score that overlooks its spatial
distribution across the body. This widespread pain is believed to be a marker of
centralization, a central nervous system process that decouples pain perception
from nociceptive input. Here, we investigated whether centralization is
manifested at the level of the brain using data from 1079 participants in the
Multidisciplinary Approach to the Study of Chronic Pelvic Pain Research Network
(MAPP) study. Participants with a clinical diagnosis of urological chronic pelvic
pain syndrome (UCPPS) were compared to pain-free controls and patients with
fibromyalgia, the prototypical centralized pain disorder. Participants completed
questionnaires capturing pain severity, function, and a body map of pain. A
subset (UCPPS N = 110; fibromyalgia N = 23; healthy control N = 49) underwent
functional and structural magnetic resonance imaging. Patients with UCPPS
reported pain ranging from localized (pelvic) to widespread (throughout the
body). Patients with widespread UCPPS displayed increased brain gray matter
volume and functional connectivity involving sensorimotor and insular cortices (P
< 0.05 corrected). These changes translated across disease diagnoses as identical
outcomes were present in patients with fibromyalgia but not pain-free controls.
Widespread pain was also associated with reduced physical and mental function
independent of pain severity. Brain pathology in patients with centralized pain
is related to pain distribution throughout the body. These patients may benefit
from interventions targeting the central nervous system.
PMID- 28692008
TI - Use of the Psychomotor Vigilance Test in Fitness for Work Assessments.
AB - OBJECTIVE: The objective of the pilot program was to evaluate the utility of the
psychomotor vigilance test (PVT) in aiding clinicians in making fitness for work
determinations. METHODS: A 10-minute PVT was incorporated into fitness for work
examinations by occupational health staff at two integrated
refining/petrochemical plants. Based on all evidence from the clinical
examination, including PVT results, clinicians made their fitness for work
determination. RESULTS: Employees who were determined to be fit for work had
significantly fewer PVT errors than did employees determined to be unfit for work
or fit for work with limitations, with t(98) = -14.71, P < 0.001. CONCLUSIONS:
The pilot assessed a new application of the PVT as an adjunct to occupational
health evaluations focused on determining fitness for work. Results demonstrated
that the PVT can be a valuable tool for this purpose.
PMID- 28692009
TI - Potential Economic Benefits of Paid Sick Leave in Reducing Absenteeism Related to
the Spread of Influenza-Like Illness.
AB - OBJECTIVE: Most U.S. employers are not required to provide paid sick leave (PSL),
and there is limited information on the economic return of providing PSL. We
estimated potential benefits to employers of PSL in reducing absenteeism related
to the spread of influenza-like illness (ILI). METHODS: We used nationally
representative data and a negative binomial random effects model to estimate the
impact of PSL in reducing overall absence due to illness or injury. We used
published data to compute the share of ILI from the total days of absence, ILI
transmission rates at workplaces, wages, and other parameters. RESULTS: Providing
PSL could have saved employers $0.63 to $1.88 billion in reduced ILI-related
absenteeism costs per year during 2007 to 2014 in 2016 dollars. CONCLUSION: These
findings might help employers consider PSL as an investment rather than as a cost
without any return.
PMID- 28692010
TI - Worksite Walkthrough Intervention: Data-driven Prevention of Workplace Violence
on Hospital Units.
AB - OBJECTIVE: The aim of this study was to describe the implementation of a data
driven, unit-based walkthrough intervention shown to be effective in reducing the
risk of workplace violence in hospitals. METHODS: A structured worksite
walkthrough was conducted on 21 hospital units. Unit-level workplace violence
data were reviewed and a checklist of possible prevention strategies and an
Action Plan form guided development of unit-specific intervention. Unit
supervisor perceptions of the walkthrough and implemented prevention strategies
were reported via questionnaires. Prevention strategies were categorized as
environmental, behavioral, or administrative. RESULTS: A majority of units
implemented strategies within 12 months' postintervention. Participants found the
walkthrough useful, practical, and worthy of continued use. CONCLUSIONS:
Structured worksite walkthroughs provide a feasible method for workplace violence
reduction in hospitals. Core elements are standardized yet flexible, promoting
fidelity and transferability of this intervention.
PMID- 28692011
TI - Far-Forward Diagnostics in Toxic Industrial Chemical and Material Exposure
Scenarios and Biomarker Identification.
AB - : This study describes key technical solutions for detecting environmental
toxicants and diagnosing adverse health effects in military operational settings
as outlined at a symposium cosponsored by the Department of Defense and the Johns
Hopkins University-Applied Physics Laboratory (October 27 to 28, 2015). Such
technologies are urgently needed in order to provide critical decision-aid tools
and prognostic assessment of potential clinical sequelae. This review summarizes
the state-of-the-science on (1) prioritization of adverse health effects, (2)
existing technologies and diagnostic tools available for use in theater, (3)
challenges to advancing diagnostic tools far-forward, and (4) the potential
utility of anchoring diagnostic tools to adverse outcome pathways. Emerging
technologies are increasingly available for physiological, environmental, and
individual exposure monitoring. Challenges to overcome in austere environments
include cold chain requirements and determination of adequate sampling intervals.
PMID- 28692012
TI - Evidence of Hippocampal Structural Alterations in Gulf War Veterans With
Predicted Exposure to the Khamisiyah Plume.
AB - OBJECTIVES: To replicate and expand our previous findings of smaller hippocampal
volumes in Gulf War (GW) veterans with predicted exposure to the Khamisiyah
plume. METHODS: Total hippocampal and hippocampal subfield volumes were
quantified from 3 Tesla magnetic resonance images in 113 GW veterans, 62 of whom
had predicted exposure as per the Department of Defense exposure models. RESULTS:
Veterans with predicted exposure had smaller total hippocampal and CA3/dentate
gyrus volumes compared with unexposed veterans, even after accounting for
potentially confounding genetic and clinical variables. Among veterans with
predicted exposure, memory performance was positively correlated with hippocampal
volume and negatively correlated with estimated exposure levels and self-reported
memory difficulties. CONCLUSIONS: These results replicate and extend our previous
finding that low-level exposure to chemical nerve agents from the Khamisiyah pit
demolition has detrimental, lasting effects on brain structure and function.
PMID- 28692013
TI - Multimorbidity and Health Care Service Utilization in the Australian Workforce:
Findings From the National Health Survey.
AB - OBJECTIVES: The aim of this study was to understand the patterns of health care
service utilization in employees with multimorbidity. METHODS: Data were obtained
from the 2011 to 2012 cross-sectional Australian National Health Survey. Past
month health care service utilization was collected for each chronic condition
from a pre-specified list. Descriptive, logistic, and Poisson regression analyses
were used. The data were weighted to produce nationally representative estimates.
RESULTS: Multimorbid employees with arthritis had higher adjusted arthritis
specific general practitioner (GP) visit rates [rate ratio (RR) = 1.7, 95%
confidence interval (95% CI) = 1.1 to 2.2, P < 0.001] than employees with
arthritis alone. Similarly, multimorbid employees with cardiovascular disease
(CVD) had higher adjusted CVD-specific specialist visit rates (RR = 1.6, 95% CI =
1.1 to 2.5, P < 0.05) and 2.5 times (95% CI = 1.5 to 4.0, P < 0.001) more CVD
specific other health professional visits than employees with CVD alone.
CONCLUSIONS: Given the increasing number of employees managing work and chronic
illnesses, these findings have implications for health services and employers.
PMID- 28692014
TI - Effect of Mindfulness-Based Stress Reduction Training on Health Care Worker
Safety: A Randomized Waitlist Controlled Trial.
AB - OBJECTIVE: The study assessed the impact of mindfulness training on occupational
safety of hospital health care workers. METHODS: The study used a randomized
waitlist-controlled trial design to test the effect of an 8-week mindfulness
based stress reduction (MBSR) course on self-reported health care worker safety
outcomes, measured at baseline, postintervention, and 6 months later. RESULTS:
Twenty-three hospital health care workers participated in the study (11 in
immediate intervention group; 12 in waitlist control group). The MBSR training
decreased workplace cognitive failures (F [1, 20] = 7.44, P = 0.013, (Equation is
included in full-text article.)) and increased safety compliance behaviors (F [1,
20] = 7.79, P = 0.011, (Equation is included in full-text article.)) among
hospital health care workers. Effects were stable 6 months following the
training. The MBSR intervention did not significantly affect participants'
promotion of safety in the workplace (F [1, 20] = 0.40, P = 0.54, (Equation is
included in full-text article.)). CONCLUSIONS: Mindfulness training may
potentially decrease occupational injuries of health care workers.
PMID- 28692015
TI - The Association Between Particulate Matter Air Pollution and Respiratory Health
in Elderly With Type 2 Diabetes Mellitus.
AB - OBJECTIVE: We investigated the association between respiratory health and
particulate matter (PM) air pollution in elderly type 2 diabetes mellitus (T2DM)
pre-, during, and post-the Chinese Lunar New Year (CLNY) holiday in Shanghai,
China. METHODS: We conducted repeated measurements of lung function and
inflammation biomarker in a cohort consisted of 60 participants with T2DM.
RESULTS: Decreased PM2.5 exposure had an effect on respiratory health by
increasing in forced expiratory flow in 1 second (FEV1) and forced vital capacity
(FVC). Positive associations between PM exposure and exhaled nitric oxide (eNO)
were observed. CONCLUSIONS: Our observations indicated that PM air pollution
exposure would exert adverse effect on respiratory health in elderly T2DM
population.
PMID- 28692016
TI - Time Well Spent: Patient Industry and Occupation Data Collection in Emergency
Departments.
AB - OBJECTIVE: No comprehensive national system tracking work-related diseases and
injuries exists in the United States. Industry and occupation (I/O) are the
missing data elements that would make existing healthcare data useful for
occupational health. The authors previously petitioned the National Uniform
Billing Committee (NUBC) to adopt I/O standards for states to consider during
their healthcare data rulemaking processes. METHODS: The NUBC asked for a pilot
study to ascertain the potential burden. The time and cost to ask I/O questions
in two hospital emergency departments was evaluated. RESULTS: Asking four I/O
questions required 48 seconds on average and cost between $520 and $623 per
Registrar per year. The annual cost for the two hospitals to gather I/O on every
patient was $4160 and $15,000. CONCLUSIONS: We conclude no undue burden compared
with the estimated $250 billion cost of occupational illnesses and injuries.
PMID- 28692017
TI - Perceived Barriers to Healthy Eating and Physical Activity Among Participants in
a Workplace Obesity Intervention.
AB - OBJECTIVE: To characterize barriers to healthy eating (BHE) and physical activity
(BPA) among participants in a workplace weight management intervention. METHODS:
Steps to health participants completed a questionnaire to ascertain barriers to
physical activity and healthy eating faced. Exploratory factor analysis was used
to determine the factor structure for BPA and BHE. The relationships of these
factors with accelerometer data and dietary behaviors were assessed using linear
regression. RESULTS: Barriers to physical activity included time constraints and
lack of interest and motivation, and to healthy eating, lack of self-control and
convenience, and lack of access to healthy foods. Higher BHE correlated with
higher sugary beverage intake but not fruit and vegetable and fat intake.
CONCLUSIONS: To improve their effectiveness, workplace weight management programs
should consider addressing and reducing barriers to healthy eating and physical
activity.
PMID- 28692018
TI - The state of gene therapy research in Africa, its significance and implications
for the future.
AB - Gene therapy has made impressive recent progress and has potential for treating a
wide range of diseases, many of which are important to Africa. However, as a
result of lack of direct public funding and skilled personnel, direct research on
gene therapy in Africa is currently limited and resources to support the endeavor
are modest. A strength of the technology is that it is based on principles of
rational design, and the tools of gene therapy are now highly versatile. For
example gene silencing and gene editing may be used to disable viral genes for
therapeutic purposes. Gene therapy may thus lead to cure from infections with HIV
1, hepatitis B virus and Ebola virus, which are of significant public health
importance in Africa. Although enthusiasm for gene therapy is justified,
significant challenges to implementing the technology remain. These include
ensuring efficient delivery of therapeutic nucleic acids to target cells,
limiting unintended effects, cost and complexity of treatment regimens. In
addition, implementation of effective legislation that will govern gene therapy
research will be a challenge. Nevertheless, it is an exciting prospect that gene
therapy should soon reach the mainstream of medical management. Participation of
African researchers in the exciting developments is currently limited, but their
involvement is important to address health problems, develop capacity and enhance
economic progress of the continent.
PMID- 28692019
TI - Bacteriophage evolution differs by host, lifestyle and genome.
AB - Bacteriophages play key roles in microbial evolution1,2, marine nutrient cycling3
and human disease4. Phages are genetically diverse, and their genome
architectures are characteristically mosaic, driven by horizontal gene transfer
with other phages and host genomes5. As a consequence, phage evolution is complex
and their genomes are composed of genes with distinct and varied evolutionary
histories6,7. However, there are conflicting perspectives on the roles of
mosaicism and the extent to which it generates a spectrum of genome diversity8 or
genetically discrete populations9,10. Here, we show that bacteriophages evolve
within two general evolutionary modes that differ in the extent of horizontal
gene transfer by an order of magnitude. Temperate phages distribute into high and
low gene flux modes, whereas lytic phages share only the lower gene flux mode.
The evolutionary modes are also a function of the bacterial host and different
proportions of temperate and lytic phages are distributed in either mode
depending on the host phylum. Groups of genetically related phages fall into
either the high or low gene flux modes, suggesting there are genetic as well as
ecological drivers of horizontal gene transfer rates. Consequently, genome
mosaicism varies depending on the host, lifestyle and genetic constitution of
phages.
PMID- 28692020
TI - Comparative effectiveness of a portion-controlled meal replacement program for
weight loss in adults with and without diabetes/high blood sugar.
AB - BACKGROUND: Individuals with type 2 diabetes (DM2) may be less successful at
achieving therapeutic weight loss than their counterparts without diabetes. This
study compares weight loss in a cohort of adults with DM2 or high blood sugar
(D/HBS) to a cohort of adults without D/HBS. All were overweight/obese and
following a reduced or low-calorie commercial weight-loss program incorporating
meal replacements (MRs) and one-on-one behavioral support. SUBJECTS/METHODS:
Demographic, weight, body composition, anthropometric, pulse and blood pressure
data were collected as part of systematic retrospective chart review studies.
Differences between cohorts by D/HBS status were analyzed using Mann-Whitney U
tests and mixed model regression. RESULTS: A total of 816 charts were included
(125 with self-reported D/HBS). The cohort with D/HBS had more males (40.8 vs
25.6%), higher BMI (39.0 vs 36.3 kg m-2) and was older (56 vs 48 years). Among
clients continuing on program, the cohorts with and without D/HBS lost, on
average, 5.6 vs 5.8 kg (NS) (5.0 vs 5.6%; P=0.005) of baseline weight at 4 weeks,
11.0 vs 11.6 kg (NS) (9.9 vs 11.1%; P=0.027) at 12 weeks and 16.3 vs 17.1 kg
(13.9 vs 15.7%; NS) at 24 weeks, respectively. In a mixed model regression
controlling for baseline weight, gender and meal plan, and an intention-to-treat
analysis, there was no significant difference in weight loss between the cohorts
at any time point. Over 70% in both cohorts lost ?5% of their baseline weight by
the final visit on their originally assigned meal plan. Both cohorts had
significant reductions from baseline in body fat, blood pressure, pulse and
abdominal circumference. CONCLUSION: Adults who were overweight/obese and with
D/HBS following a commercial weight-loss program incorporating MRs and one-on-one
behavioral support achieved therapeutic weight loss. The program was equally
effective for weight loss and reductions in cardiometabolic risk factors among
adults with and without D/HBS.
PMID- 28692021
TI - Additional families of orange carotenoid proteins in the photoprotective system
of cyanobacteria.
AB - The orange carotenoid protein (OCP) is a structurally and functionally modular
photoactive protein involved in cyanobacterial photoprotection. Using
phylogenomic analysis, we have revealed two new paralogous OCP families, each
distributed among taxonomically diverse cyanobacterial genomes. Based on
bioinformatic properties and phylogenetic relationships, we named the new
families OCP2 and OCPx to distinguish them from the canonical OCP that has been
well characterized in Synechocystis, denoted hereafter as OCP1. We report the
first characterization of a carotenoprotein photoprotective system in the
chromatically acclimating cyanobacterium Tolypothrix sp. PCC 7601, which encodes
both OCP1 and OCP2 as well as the regulatory fluorescence recovery protein (FRP).
OCP2 expression could only be detected in cultures grown under high irradiance,
surpassing expression levels of OCP1, which appears to be constitutive; under low
irradiance, OCP2 expression was only detectable in a Tolypothrix mutant lacking
the RcaE photoreceptor required for complementary chromatic acclimation. In vitro
studies show that Tolypothrix OCP1 is functionally equivalent to Synechocystis
OCP1, including its regulation by Tolypothrix FRP, which we show is structurally
similar to the dimeric form of Synechocystis FRP. In contrast, Tolypothrix OCP2
shows both faster photoconversion and faster back-conversion, lack of regulation
by the FRP, a different oligomeric state (monomer compared to dimer for OCP1) and
lower fluorescence quenching of the phycobilisome. Collectively, these findings
support our hypothesis that the OCP2 is relatively primitive. The OCP2 is
transcriptionally regulated and may have evolved to respond to distinct
photoprotective needs under particular environmental conditions such as high
irradiance of a particular light quality, whereas the OCP1 is constitutively
expressed and is regulated at the post-translational level by FRP and/or
oligomerization.
PMID- 28692022
TI - Gender differences in physical function and muscle mass change in patients
undergoing allogeneic hematopoietic stem cell transplantation.
PMID- 28692023
TI - Trust, not education, is the key to consent in hematopoietic cell transplant: in
response to D'Souza, Pasquini and Spellecy.
PMID- 28692024
TI - No report on Zika virus infection in EBMT registry: Infectious Diseases Working
Party statement.
PMID- 28692025
TI - Cerebral adenovirus endotheliitis presenting as posterior reversible
encephalopathy syndrome after allogeneic stem cell transplantation.
PMID- 28692026
TI - Association between single nucleotide polymorphisms of tumor necrosis factor gene
and grade II-IV acute GvHD: a systematic review and meta-analysis.
AB - Acute GvHD (aGvHD) complicates up to 50% of allogeneic hematopoietic cell
transplants and pre-transplant estimation of its risk can guide prophylaxis,
monitoring and early intervention strategies. Inspired by the role of tumor
necrosis factor alpha (TNFalpha) in the pathogenesis of aGvHD and the
inconsistency of the association studies exploring single nucleotide
polymorphisms (SNPs) of the TNF gene, we conducted a systematic review and meta
analysis of the available reports using PubMed and EMBASE. Original human studies
reporting on the association between recipient TNF SNPs and grade II-IV aGvHD in
a format convertible to effect size and confidence interval were included. One of
the two most widely investigated SNPs (rs361525G>A) was marginally associated
with increased risk of grade II-IV aGvHD in random-effects meta-analysis of six
studies (627 patients in total, risk ratio=1.29, 95% confidence interval=0.99
1.69, P=0.06). If this result is validated in a large cohort with uniform
conditioning and GvHD prophylaxis, TNF rs361525G>A may become a useful tool for
aGvHD risk estimation before the transplant.
PMID- 28692027
TI - JACIE accreditation from the perspective of an accredited centre.
PMID- 28692028
TI - In search of the optimal platform for Post-Allogeneic SCT immunotherapy in
relapsed multiple myeloma: a systematic review.
AB - Allogeneic stem cell transplantation (allo-SCT) has the potential to induce
sustained remissions in patients with multiple myeloma (MM). Currently, allo-SCT
is primarily performed in high-risk MM patients, most often in the setting of
early relapse after first-line therapy with autologous SCT. However, the
implementation of allo-SCT for MM is jeopardized by high treatment-related
mortality (TRM) rates as well as high relapse rates. In this systematic review,
we aimed to identify a safe allo-SCT strategy that has optimal 1-year results
regarding mortality, relapse and severe GvHD, creating opportunities for post
transplantation strategies to maintain remissions in the high-risk group of
relapsed MM patients. Eleven studies were included. Median PFS ranged from 5.2 to
36.8 months and OS was 13.0 to 63.0 months. The relapse related mortality at 1
year varied between 0 and 50% and TRM between 8 and 40%. Lowest GvHD incidences
were reported for conditioning regimens with T-cell depletion using ATG or graft
CD34+ selection. Similar strategies could lay the foundation for a post
transplant immune platform, this should be further evaluated in prospective
clinical trials.
PMID- 28692029
TI - Pre-autologous transplantation PET/CT using Deauville criteria is an independent
predictor of progression in relapsed refractory classical Hodgkin lymphoma.
PMID- 28692030
TI - HLA-mismatched bone marrow transplantation in severe aplastic anemia.
PMID- 28692031
TI - Cord blood attached segment: is this a relevant quality control to predict a good
hematopoietic stem cell graft?
PMID- 28692032
TI - Epigenetic silencing of microRNA-137 enhances ASCT2 expression and tumor
glutamine metabolism.
AB - Tumor cells must activate specific transporters to meet their increased glutamine
metabolic demands. Relative to other glutamine transporters, the ASC family
transporter 2 (ASCT2, also called SLC1A5) is profoundly elevated in a wide
spectrum of human cancers to coordinate metabolic reprogramming and malignant
transformation. Understanding the molecular mechanisms whereby tumor cells
frequently upregulate this transporter is therefore vital to develop potential
strategies for transporter-targeted therapies. Combining in-silico algorithms
with systemic experimental screening, we herein identify the tumor suppressor
microRNA, miR-137, as an essential regulator that targets ASCT2 and cancer cell
glutamine metabolism. Metabolic analysis shows that miR-137 derepression, similar
to ASCT2 inactivation, significantly inhibits glutamine consumption and TCA cycle
anaplerosis. Mechanistically, methyl-CpG-binding protein 2 (MeCP2) and DNA
methyltransferases (DNMTs) cooperate to promote active methylation of the miR-137
promoter and inhibit its transcription, conversely reactivating ASCT2 expression
and glutamine metabolism. Moreover, expression between miR-137 and ASCT2 is
inversely correlated in tumor specimens from multiple cancer types, and ectopic
ASCT2 expression markedly rescued miR-137 suppression of tumorigenesis. These
findings thus elucidate a previously unreported mechanism responsible for ASCT2
deregulation in human cancers and identify ASCT2 as a critical downstream
effector of miR-137, revealing a molecular link between DNA methylation, microRNA
and tumor metabolism.
PMID- 28692033
TI - Spontaneous loss of B lineage transcription factors leads to pre-B leukemia in
Ebf1+/-Bcl-xLTg mice.
AB - Early B-cell factor 1 (EBF1) plays a central role in B-cell lineage specification
and commitment. Loss of this critical transcription factor is strongly associated
with high-risk, relapsed and therapy-resistant B-cell-acute lymphoblastic
leukemia, especially in children. However, Ebf1 haploinsufficient mice exhibit a
normal lifespan. To determine whether prolonged survival of B cells would enable
tumorigenesis in Ebf1 haploinsufficient animals, we generated Ebf1+/-Bcl-xLTg
mice, which express the anti-apoptotic factor Bcl-xL in B cells. Approximately
half of Ebf1+/-Bcl-xLTg mice develop aggressive oligoclonal leukemia as they age,
which engrafts in congenic wild-type recipients without prior conditioning. The
neoplastic cells display a pre-B phenotype and express early developmental- and
natural killer cell/myeloid-markers inappropriately. In addition, we found tumor
cell-specific loss of several transcription factors critical for maintaining
differentiation: EBF1, TCF3 and RUNX1. However, in the majority of tumors, loss
of Ebf1 expression was not due to loss of heterozygosity. This is the first
spontaneous mouse model of pre-B leukemia to demonstrate inappropriate expression
of non-B-cell-specific genes associated with loss of Ebf1, Tcf3 and Runx1
expression.
PMID- 28692034
TI - miR-200b inhibits proliferation and metastasis of breast cancer by targeting
fucosyltransferase IV and alpha1,3-fucosylated glycans.
AB - Aberrant protein fucosylation is associated with cancer malignancy.
Fucosyltransferase IV (FUT4) is the key enzyme catalyzing the biosynthesis of
alpha1,3-linkage fucosylated glycans carried by glycoproteins on the cell
surface, such as the tumor-associated sugar antigen Lewis Y (LeY). An abnormal
increase in the levels of FUT4 and LeY is observed in many cancers and correlated
with cell proliferation and metastasis. Some microRNAs (miRNAs) are known to
negatively regulate gene expression. FUT4 is an oncogenic glycogene, and thus it
is important to identify the specific miRNA targeting FUT4. In current study, we
first identified miR-200b as a specific miRNA that inhibited FUT4 expression. We
found that miR-200b level was decreased, whereas that of FUT4 was increased in
tissues and serum of breast cancer compared with that in the control by real-time
PCR, western blotting and enzyme-linked immunosorbent assay. The alterations of
miR-200b and FUT4 level were recovered after chemotherapy. The results also
showed that miR-200b suppressed FUT4 expression and inhibited tumor growth and
metastasis in MCF-7 and MDA-MB-231 breast cancer cells, as well as in the
xenografted tumor tissues and metastatic lung tissues. miR-200b decreased the
alpha1,3-fucosylation and LeY biosynthesis on epidermal growth factor receptor
(EGFR), as well as inactivation of EGFR and downstream phosphoinositide-3
kinase/Akt signaling pathway. In conclusion, the study highlights that FUT4 could
apply as a novel target for miR-200b that suppress the proliferation and
metastasis of breast cancer cells by reducing alpha1,3-fucosylation and LeY
biosynthesis of glycoproteins. miR-200b and FUT4 are potential diagnostic and
therapeutic targets for breast cancer.
PMID- 28692035
TI - Role of integrin-linked kinase in regulating the protein stability of the MUC1-C
oncoprotein in pancreatic cancer cells.
AB - MUC1-C overexpression has been associated with the progression of pancreatic
tumors by promoting the aggressive and metastatic phenotypes. As MUC1 is a STAT3
target gene, STAT3 plays a major role in regulating MUC1-C expression. In this
study, we report an alternative mechanism by which integrin-linked kinase (ILK)
post-transcriptionally modulates the expression of MUC1-C by maintaining its
protein stability in pancreatic cancer cells. We found that ILK acts in concert
with STAT3 to facilitate IL-6-mediated upregulation of MUC1-C; ILK depletion was
equally effective as STAT3 depletion in abolishing IL-6-induced MUC1-C
overexpression without disturbing the phosphorylation or cellular distribution of
STAT3. Conversely, ectopic expression of constitutively active ILK increased MUC1
C expression, though this increase was not noted with kinase-dead ILK. This
finding suggests the requirement of the kinase activity of ILK in regulating MUC1
C stability, which was confirmed by using the ILK kinase inhibitor T315.
Furthermore, our data suggest the involvement of protein kinase C (PKC)delta in
mediating the suppressive effect of ILK inhibition on MUC1-C repression. For
example, co-immunoprecipitation analysis indicated that ILK depletion-mediated
MUC1-C phosphorylation was accompanied by increased phosphorylation of PKCdelta
at the activation loop Thr-507 and increased binding of PKCdelta to MUC1-C.
Conversely, ILK overexpression resulted in decreased PKCdelta phosphorylation.
From a mechanistic perspective, the present finding, together with our recent
report that ILK controls the expression of oncogenic KRAS through a regulatory
loop, underscores the pivotal role of ILK in promoting pancreatic cancer
progression.
PMID- 28692036
TI - Neoadjuvant chemotherapy affects molecular classification of colorectal tumors.
AB - The recent discovery of 'molecular subtypes' in human primary colorectal cancer
has revealed correlations between subtype, propensity to metastasize and response
to therapy. It is currently not known whether the molecular tumor subtype is
maintained after distant spread. If this is the case, molecular subtyping of the
primary tumor could guide subtype-targeted therapy of metastatic disease. In this
study, we classified paired samples of primary colorectal carcinomas and their
corresponding liver metastases (n=129) as epithelial-like or mesenchymal-like,
using a recently developed immunohistochemistry-based classification tool. We
observed considerable discordance (45%) in the classification of primary tumors
and their liver metastases. Discordant classification was significantly
associated with the use of neoadjuvant chemotherapy. Furthermore, gene expression
analysis of chemotherapy-exposed versus chemotherapy naive liver metastases
revealed expression of a mesenchymal program in pre-treated tumors. To explore
whether chemotherapy could cause gene expression changes influencing molecular
subtyping, we exposed patient-derived colonospheres to six short cycles of 5
fluorouracil. Gene expression profiling and signature enrichment analysis
subsequently revealed that the expression of signatures identifying mesenchymal
like tumors was strongly increased in chemotherapy-exposed tumor cultures.
Unsupervised clustering of large cohorts of human colon tumors with the
chemotherapy-induced gene expression program identified a poor prognosis
mesenchymal-like subgroup. We conclude that neoadjuvant chemotherapy induces a
mesenchymal phenotype in residual tumor cells and that this may influence the
molecular classification of colorectal tumors.
PMID- 28692037
TI - SRGN-TGFbeta2 regulatory loop confers invasion and metastasis in triple-negative
breast cancer.
AB - Patients with triple-negative breast cancers (TNBC) are at a high risk for a
recurrent or metastatic disease, and the molecular mechanisms associated with
this risk are unclear. Proteoglycan serglycin (SRGN) proteins are involved in
tumor metastasis, but their role in TNBC has not yet been elucidated. This study
investigates the SRGN gene expression and how it regulates TGFbeta2 and the
downstream signaling of TGFbeta2 in TNBC cells and tissues. Our results show that
SRGN mRNA and protein expression levels were significantly higher in TNBC cell
lines and tumor tissues than that in non-TNBC cells and tissues. We inhibited
SRGN expression and protein secretion using shRNA and we observed this inhibited
the invasive motility of TNBC cancer cells in vitro and metastasis of TNBC cancer
cells in vivo. SRGN protein treatment increased the expression and secretion of
transforming growth factor-beta2 (TGFbeta2) by activating CD44/CREB1 signaling
and promoted epithelial-to-mesenchymal transition in TNBC cells. Moreover,
TGFbeta2 treatment increased the mRNA and protein expression of the SRGN gene by
activating Smad3 to target the SRGN relative promoter domain in TNBC cells. Our
findings demonstrate that SRGN interacts with TGFbeta2 which regulates TNBC
metastasis via the autocrine and paracrine routes. SRGN could serve as a
potential target for development of agents or therapeutics for the TNBC.
PMID- 28692038
TI - PAR-TERRA directs homologous sex chromosome pairing.
AB - In mammals, homologous chromosomes rarely pair outside meiosis. One exception is
the X chromosome, which transiently pairs during X-chromosome inactivation (XCI).
How two chromosomes find each other in 3D space is not known. Here, we reveal a
required interaction between the X-inactivation center (Xic) and the telomere in
mouse embryonic stem (ES) cells. The subtelomeric, pseudoautosomal regions (PARs)
of the two sex chromosomes (X and Y) also undergo pairing in both female and male
cells. PARs transcribe a class of telomeric RNA, dubbed PAR-TERRA, which accounts
for a vast majority of all TERRA transcripts. PAR-TERRA binds throughout the
genome, including to the PAR and Xic. During X-chromosome pairing, PAR-TERRA
anchors the Xic to the PAR, creating a 'tetrad' of pairwise homologous
interactions (Xic-Xic, PAR-PAR, and Xic-PAR). Xic pairing occurs within the
tetrad. Depleting PAR-TERRA abrogates pairing and blocks initiation of XCI,
whereas autosomal PAR-TERRA induces ectopic pairing. We propose a 'constrained
diffusion model' in which PAR-TERRA creates an interaction hub to guide Xic
homology searching during XCI.
PMID- 28692039
TI - Revealing crystalline domains in a mollusc shell single-crystalline prism.
AB - Biomineralization integrates complex processes leading to an extraordinary
diversity of calcareous biomineral crystalline architectures, in intriguing
contrast with the consistent presence of a sub-micrometric granular structure.
Hence, gaining access to the crystalline architecture at the mesoscale, that is,
over a few granules, is key to building realistic biomineralization scenarios.
Here we provide the nanoscale spatial arrangement of the crystalline structure
within the 'single-crystalline' prisms of the prismatic layer of a Pinctada
margaritifera shell, exploiting three-dimensional X-ray Bragg ptychography
microscopy. We reveal the details of the mesocrystalline organization, evidencing
a crystalline coherence extending over a few granules. We additionally prove the
existence of larger iso-oriented crystalline domains, slightly misoriented with
respect to each other, around one unique rotation axis, and whose shapes are
correlated with iso-strain domains. The highlighted mesocrystalline properties
support recent biomineralization models involving partial fusion of oriented
nanoparticle assembly and/or liquid droplet precursors.
PMID- 28692040
TI - Valley magnetoelectricity in single-layer MoS2.
AB - The magnetoelectric (ME) effect, the phenomenon of inducing magnetization by
application of an electric field or vice versa, holds great promise for magnetic
sensing and switching applications. Studies of the ME effect have so far focused
on the control of the electron spin degree of freedom (DOF) in materials such as
multiferroics and conventional semiconductors. Here, we report a new form of the
ME effect based on the valley DOF in two-dimensional Dirac materials. By breaking
the three-fold rotational symmetry in single-layer MoS 2 via a uniaxial stress,
we have demonstrated the pure electrical generation of valley magnetization in
this material, and its direct imaging by Kerr rotation microscopy. The observed
out-of-plane magnetization is independent of in-plane magnetic field, linearly
proportional to the in-plane current density, and optimized when the current is
orthogonal to the strain-induced piezoelectric field. These results are fully
consistent with a theoretical model of valley magnetoelectricity driven by Berry
curvature effects. Furthermore, the effect persists at room temperature, opening
possibilities for practical valleytronic devices.
PMID- 28692041
TI - Strength of the repulsive part of the interatomic potential determines fragility
in metallic liquids.
AB - The dynamical behaviour of liquids is frequently characterized by the fragility,
which can be defined from the temperature dependence of the shear viscosity, eta
(ref. ). For a strong liquid, the activation energy for eta changes little with
cooling towards the glass transition temperature, Tg. The change is much greater
in fragile liquids, with the activation energy becoming very large near Tg. While
fragility is widely recognized as an important concept-believed, for example, to
play an important role in glass formation-the microscopic origin of fragility is
poorly understood. Here, we present new experimental evidence showing that
fragility reflects the strength of the repulsive part of the interatomic
potential, which can be determined from the steepness of the pair distribution
function near the hard-sphere cutoff. On the basis of an analysis of scattering
data from ten different metallic alloy liquids, we show that stronger liquids
have steeper repulsive potentials.
PMID- 28692042
TI - Excitation-wavelength-dependent small polaron trapping of photoexcited carriers
in alpha-Fe2O3.
AB - Small polaron formation is known to limit ground-state mobilities in metal oxide
photocatalysts. However, the role of small polaron formation in the photoexcited
state and how this affects the photoconversion efficiency has yet to be
determined. Here, transient femtosecond extreme-ultraviolet measurements suggest
that small polaron localization is responsible for the ultrafast trapping of
photoexcited carriers in haematite (alpha-Fe2O3). Small polaron formation is
evidenced by a sub-100 fs splitting of the Fe 3p core orbitals in the Fe M2,3
edge. The small polaron formation kinetics reproduces the triple-exponential
relaxation frequently attributed to trap states. However, the measured spectral
signature resembles only the spectral predictions of a small polaron and not the
pre-edge features expected for mid-gap trap states. The small polaron formation
probability, hopping radius and lifetime varies with excitation wavelength,
decreasing with increasing energy in the t2g conduction band. The excitation
wavelength-dependent localization of carriers by small polaron formation is
potentially a limiting factor in haematite's photoconversion efficiency.
PMID- 28692043
TI - Cross talk between progesterone receptors and retinoic acid receptors in
regulation of cytokeratin 5-positive breast cancer cells.
AB - Half of estrogen receptor-positive breast cancers contain a subpopulation of
cytokeratin 5 (CK5)-expressing cells that are therapy resistant and exhibit
increased cancer stem cell (CSC) properties. We and others have demonstrated that
progesterone (P4) increases CK5+ breast cancer cells. We previously discovered
that retinoids block P4 induction of CK5+ cells. Here we investigated the
mechanisms by which progesterone receptors (PR) and retinoic acid receptors (RAR)
regulate CK5 expression and breast CSC activity. After P4 treatment, sorted CK5+
compared to CK5- cells were more tumorigenic in vivo. In vitro, P4-treated breast
cancer cells formed larger mammospheres and silencing of CK5 using small hairpin
RNA abolished this P4-dependent increase in mammosphere size. Retinoic acid (RA)
treatment blocked the P4 increase in CK5+ cells and prevented the P4 increase in
mammosphere size. Dual small interfering RNA (siRNA) silencing of RARalpha and
RARgamma reversed RA blockade of P4-induced CK5. Using promoter deletion
analysis, we identified a region 1.1 kb upstream of the CK5 transcriptional start
site that is necessary for P4 activation and contains a putative progesterone
response element (PRE). We confirmed by chromatin immunoprecipitation that P4
recruits PR to the CK5 promoter near the -1.1 kb essential PRE, and also to a
proximal region near -130 bp that contains PRE half-sites and a RA response
element (RARE). RA induced loss of PR binding only at the proximal site.
Interestingly, RARalpha was recruited to the -1.1 kb PRE and the -130 bp PRE/RARE
regions with P4, but not RA alone or RA plus P4. Treatment of breast cancer
xenografts in vivo with the retinoid fenretinide reduced the accumulation of CK5+
cells during estrogen depletion. This reduction, together with the inhibition of
CK5+ cell expansion through RAR/PR cross talk, may explain the efficacy of
retinoids in prevention of some breast cancer recurrences.
PMID- 28692044
TI - Pyruvate dehydrogenase kinase 4 exhibits a novel role in the activation of mutant
KRAS, regulating cell growth in lung and colorectal tumour cells.
AB - RAS signalling is involved in the control of several metabolic pathways including
glycolysis, mitochondrial respiration and glutamine metabolism. Importantly, we
have found here that loss of PDHK4, a key regulator of the pyruvate dehydrogenase
complex, caused a profound cell growth inhibition in tumour cells harbouring KRAS
mutations. Using isogenic cells and a panel of colorectal and lung cell lines we
demonstrated that KRAS mutant cells showed a dependency on PDHK4 whereas KRAS
wild-type cells were significantly resistant to PDHK4 knockdown. We have found
that PDHK4 plays a role in the post-translational regulation of mutant KRAS
activity. Depletion of PDHK4 causes disruption of KRAS cellular localization, a
reduction in KRAS activity which, in turn, results in reduced MAPK signalling.
Interestingly, PDHK4 and KRAS depletion resulted in a similar metabolic phenotype
consisting of a reduction of glucose and fatty acid oxidation. Moreover, stable
expression of PDHK4 increased localization of activated KRAS at the plasma
membrane and induced tumour cell growth in vitro and in vivo. Taken together
these data support a model where PDHK4 regulates KRAS signalling and its
tumorigenic properties and suggest that inhibition of PDHK4 could represent a
novel therapeutic strategy to target KRAS mutant colorectal and lung cancers.
PMID- 28692045
TI - Impact of histone demethylase KDM3A-dependent AP-1 transactivity on
hepatotumorigenesis induced by PI3K activation.
AB - Epigenetic gene regulation linked to oncogenic pathways is an important focus of
cancer research. KDM3A, a histone H3 lysine 9 (H3K9) demethylase, is known to
have a pro-tumorigenic function. Here, we showed that KDM3A contributes to liver
tumor formation through the phosphatidylinositol 3-kinase (PI3K) pathway, which
is often activated in hepatocellular carcinoma. Loss of Kdm3a attenuated tumor
formation in Pik3ca transgenic (Tg) mouse livers. Transcriptome analysis of pre
cancerous liver tissues revealed that the expression of activator protein 1 (AP
1) target genes was induced by PI3K activation, but blunted upon Kdm3a ablation.
Particularly, the expression of Cd44, a liver cancer stem marker, was regulated
by AP-1 in a Kdm3a-dependent manner. We identified Cd44-positive hepatocytes with
epithelial-mesenchymal transition-related expression profiles in the Pik3ca Tg
liver and confirmed their in vivo tumorigenic capacity. Notably, the number and
tumor-initiating capacity of Cd44-positive hepatocytes were governed by Kdm3a. As
a mechanism in Kdm3a-dependent AP-1 transcription, Kdm3a recruited c-Jun to the
AP-1 binding sites of Cd44, Mmp7 and Pdgfrb without affecting c-Jun expression.
Moreover, Brg1, a component of the SWI/SNF chromatin remodeling complex,
interacted with c-Jun in a Kdm3a-dependent manner and was bound to the AP-1
binding site of these genes. Finally, KDM3A and c-JUN were co-expressed in 33% of
human premalignant lesions with PI3K activation. Our data suggest a critical role
for KDM3A in the PI3K/AP-1 oncogenic axis and propose a novel strategy for
inhibition of KDM3A against liver tumor development under PI3K pathway
activation.
PMID- 28692046
TI - Inhibition of the androgen receptor induces a novel tumor promoter, ZBTB46, for
prostate cancer metastasis.
AB - Current therapeutic regimens for prostate cancer focus on targeting androgen
receptor (AR) signaling. However, the AR is a key factor in luminal epithelium
differentiation and was shown to have a role as a tumor suppressor. Thus, its
inhibition may activate oncogenic pathways that contribute to metastatic
castration-resistant prostate cancer (CRPC). Herein, we report a novel tumor
promoter, ZBTB46, which is negatively regulated by AR signaling via microRNA
(miR)-1-mediated downregulation. ZBTB46 is associated with malignant prostate
cancer and is essential for metastasis. Its overexpression can overcome the
antitumor effects of miR-1 and promote androgen-independent proliferation. We
demonstrated that ZBTB46 can transcriptionally regulate SNAI1, a key epithelial
to-mesenchymal transition (EMT) driver, which could contribute to induction of
the EMT after androgen-deprivation therapy and metastasis. Our findings are
supportive of the model that disruption of AR's function may predispose prostate
cancer to progress to metastatic CRPC.
PMID- 28692048
TI - Increased expression of programmed cell death protein 1 on NK cells inhibits NK
cell-mediated anti-tumor function and indicates poor prognosis in digestive
cancers.
AB - Abnormal expression of activating/inhibitory receptors leads to natural killer
(NK) cells dysfunction in tumor. Here we show that programmed cell death protein
1 (PD-1), a well-known immune checkpoint of T cells, is highly expressed on
peripheral and tumor-infiltrating NK cells from patients with digestive cancers
including esophageal, liver, colorectal, gastric and biliary cancer. The
increased PD-1 expression on NK cells indicates poorer survival in esophageal and
liver cancers. Blocking PD-1/PD-L1 signaling markedly enhances cytokines
production and degranulation and suppresses apoptosis of NK cells in vitro. PD
1/PD-L1 exerts inhibitory effect through repressing the activation of PI3K/AKT
signaling in NK cells. More importantly, a PD-1 blocking antibody was found to
significantly suppress the growth of xenografts in nude mice, and this inhibition
of tumor growth was completely abrogated by NK depletion. These findings strongly
suggested that PD-1 is an inhibitory regulator of NK cells in digestive cancers.
PD-1 blockade might be an efficient strategy in NK cell-based tumor
immunotherapy.
PMID- 28692047
TI - Androgen induces G3BP2 and SUMO-mediated p53 nuclear export in prostate cancer.
AB - The androgen receptor (AR) has a central role in prostate cancer progression,
particularly treatment-resistance disease including castration-resistant prostate
cancer. Loss of the p53 tumor suppressor, a nuclear transcription factor, is also
known to contribute to prostate malignancy. Here we report that p53 is
translocated to the cytoplasm by androgen-mediated induction of G3BP2, a newly
described direct target gene of AR. G3BP2 induces both cell cycle progression and
blocks apoptosis. Translocation of p53 is regulated by androgen-dependent
sumoylation mediated by the G3BP2-interacting SUMO-E3 ligase, RanBP2. G3BP2
knockdown results in reduced tumor growth and increased nuclear p53 accumulation
in mouse xenograft models of prostate cancer with or without long-term androgen
deprivation. Moreover, strong cytoplasmic p53 localization is correlated
clinically with elevated G3BP2 expression and predicts poor prognosis and disease
progression to the hormone-refractory state. Our findings reveal a new AR
mediated mechanism of p53 inhibition that promotes treatment-resistant prostate
cancer.
PMID- 28692049
TI - Mdm2 selectively suppresses DNA damage arising from inhibition of topoisomerase
II independent of p53.
AB - Mdm2 is often overexpressed in tumors that retain wild-type TP53 but may affect
therapeutic response independently of p53. Herein is shown that tumor cells with
MDM2 amplification are selectively resistant to treatment with topoisomerase II
poisons but not other DNA damaging agents. Tumor cells that overexpress Mdm2 have
reduced DNA double-strand breaks in response to doxorubicin or etoposide. This
latter result is not due to altered drug uptake. The selective attenuation of DNA
damage in response to these agents is dependent on both Mdm2 levels and an intact
ubiquitin ligase function. These findings reveal a novel, p53-independent
activity of Mdm2 and have important implications for the choice of
chemotherapeutic agents in the treatment of Mdm2-overexpressing tumors.
PMID- 28692050
TI - Crosstalk between NRF2 and HIPK2 shapes cytoprotective responses.
AB - Homeodomain interacting protein kinase-2 (HIPK2) is a member of the HIPK family
of stress-responsive kinases that modulates cell growth, apoptosis, proliferation
and development. HIPK2 has several well-characterised tumour suppressor roles,
but recent studies suggest it can also contribute to tumour progression, although
the underlying mechanisms are unknown. Herein, we have identified novel crosstalk
between HIPK2 and the cytoprotective transcription factor NRF2. We show that
HIPK2 is a direct transcriptional target of NRF2, identifying a functional NRF2
binding site in the HIPK2 gene locus and demonstrating for the first time a
transcriptional mode of regulation for this kinase. In addition, HIPK2 is
required for robust NRF2 responsiveness in cells and in vivo. By using both gain
of-function and loss-of-function approaches, we demonstrate that HIPK2 can elicit
a cytoprotective response in cancer cells via NRF2. Our results have uncovered a
new downstream effector of HIPK2, NRF2, which is frequently activated in human
tumours correlating with chemoresistance and poor prognosis. Furthermore, our
results suggest that modulation of either HIPK2 levels or activity could be
exploited to impair NRF2-mediated signalling in cancer cells, and thus sensitise
them to chemotherapeutic drugs.
PMID- 28692051
TI - Transcriptional regulation of ataxia-telangiectasia and Rad3-related protein by
activated p21-activated kinase-1 protects keratinocytes in UV-B-induced
premalignant skin lesions.
AB - Sun-induced skin lesions, in particular actinic keratosis, are generally
considered as premalignant skin lesions that can progress into squamous cell
carcinoma (SCC) and invasive SCC if left untreated. Therefore, understanding the
molecular mechanisms by which the ultraviolet-B (UV-B)-exposed cells are being
protected and the signaling pathways that promote the progression of certain
premalignant skin lesions to malignant lesions will permit us to prevent or cure
skin cancers. In the current study, we found that phospho-p21-activated kinase-1
(Pak1) and Pak1 expression was high in clinical samples of sunlight-induced
premalignant skin lesions assessed by immunohistochemistry. Further, we observed
that phospho-Pak1 and Pak1 levels are high in UV-B-exposed hairless SKH mouse
model skin samples as compared with unexposed skin tissue. Our results from cell
line and animal models showed that Pak1 is activated in response to UV-B
radiation, and this activated Pak1 translocates from the cytoplasm to the
nucleus. Inside the nucleus, Pak1 via C-Fos binds to a specific promoter region
of DNA repair kinase ATR (ataxia-telangiectasia and Rad3-related protein) and
acts as a transcriptional regulator of ATR. Results from our analysis showed that
Pak1 overexpression, knockdown and Pak1 knockout cell line models showed that
Pak1 confers protection to keratinocytes from UV-B-induced apoptosis and DNA
damage via ATR. To our knowledge, this is the first study that evaluates the
functional and clinical significance of a signaling molecule, Pak1, in sun
induced premalignant skin lesions and indicates that increased Pak1 activation
and expression could serve as an early warning sign of progression toward non
melanoma skin cancer, if ignored.
PMID- 28692052
TI - Disrupting G6PD-mediated Redox homeostasis enhances chemosensitivity in
colorectal cancer.
AB - Glucose-6-phosphate dehydrogenase (G6PD) is a key enzyme that generates NADPH to
maintain reduced glutathione (GSH), which scavenges reactive oxygen species (ROS)
to protect cancer cell from oxidative damage. In this study, we mainly
investigate the potential roles of G6PD in colorectal cancer (CRC) development
and chemoresistance. We discover that G6PD is overexpressed in CRC cells and
patient specimens. High expression of G6PD predicts poor prognosis and correlated
with poor outcome of oxaliplatin-based first-line chemotherapy in patients with
CRC. Suppressing G6PD decreases NADPH production, lowers GSH levels, impairs the
ability to scavenge ROS levels, and enhances oxaliplatin-induced apoptosis in CRC
via ROS-mediated damage in vitro. In vivo experiments further shows that
silencing G6PD with lentivirus or non-viral gene delivery vector enhances
oxaliplatin anti-tumor effects in cell based xenografts and PDX models. In
summary, our finding indicated that disrupting G6PD-mediated NADPH homeostasis
enhances oxaliplatin-induced apoptosis in CRC through redox modulation. Thus,
this study indicates that G6PD is a potential prognostic biomarker and a
promising target for CRC therapy.
PMID- 28692053
TI - Pre-45s rRNA promotes colon cancer and is associated with poor survival of CRC
patients.
AB - One characteristic of cancer cells is the abnormally high rate of cell metabolism
to sustain their enhanced proliferation. However, the behind mechanism of this
phenomenon is still elusive. Here we find that enhanced precursor 45s ribosomal
RNA (pre-45s rRNA) is one of the core mechanisms in promoting the pathogenesis of
colorectal cancer (CRC). Pre-45s rRNA expression is significantly higher in
primary CRC tumor tissues samples and cancer cell lines compared with the non
tumorous colon tissues, and is associated with tumor sizes. Knockdown of pre-45s
rRNA inhibits G1/S cell-cycle transition by stabilizing p53 through inducing
murine double minute 2 (MDM2) and ribosomal protein L11 (RpL11) interaction. In
addition, we revealed that high rate of cancer cell metabolism triggers the
passive release of calcium ion from endoplasmic reticulum to the cytoplasm. The
elevated calcium ion in the cytoplasm activates the signaling cascade of
calcium/calmodulin-dependent protein kinase II, ribosomal S6 kinase (S6K) and
ribosomal S6K (CaMKII-S6K-UBF). The activated UBF promotes the transcription of
rDNA, which therefore increases pre-45s rRNA. Disruption of CaMKII-S6K-UBF axis
by either RNAi or pharmaceutical approaches leads to reduction of pre-45s rRNA
expression, which subsequently suppresses cell proliferation in colon cancer
cells by causing cell-cycle arrest. Knockdown of APC activates CaMKII-S6K-UBF
cascade and thus enhances pre-45s rRNA expression. Moreover, the high expression
level of pre-45s rRNA is associated with poor survival of CRC patients in two
independent cohorts. Our study identifies a novel mechanism in CRC pathogenesis
mediated by pre-45s rRNA and a prognostic factor of pre-45s rRNA in CRC patients.
PMID- 28692054
TI - Modeling cancer driver events in vitro using barrier bypass-clonal expansion
assays and massively parallel sequencing.
AB - The information on candidate cancer driver alterations available from public
databases is often descriptive and of limited mechanistic insight, which poses
difficulties for reliable distinction between true driver and passenger events.
To address this challenge, we performed in-depth analysis of whole-exome
sequencing data from cell lines generated by a barrier bypass-clonal expansion
(BBCE) protocol. The employed strategy is based on carcinogen-driven
immortalization of primary mouse embryonic fibroblasts and recapitulates early
steps of cell transformation. Among the mutated genes were almost 200 COSMIC
Cancer Gene Census genes, many of which were recurrently affected in the set of
25 immortalized cell lines. The alterations affected pathways regulating DNA
damage response and repair, transcription and chromatin structure, cell cycle and
cell death, as well as developmental pathways. The functional impact of the
mutations was strongly supported by the manifestation of several known cancer
hotspot mutations among the identified alterations. We identified a new set of
genes encoding subunits of the BAF chromatin remodeling complex that exhibited
Ras-mediated dependence on PRC2 histone methyltransferase activity, a finding
that is similar to what has been observed for other BAF subunits in cancer cells.
Among the affected BAF complex subunits, we determined Smarcd2 and Smarcc1 as
putative driver candidates not yet fully identified by large-scale cancer genome
sequencing projects. In addition, Ep400 displayed characteristics of a driver
gene in that it showed a mutually exclusive mutation pattern when compared with
mutations in the Trrap subunit of the TIP60 complex, both in the cell line panel
and in a human tumor data set. We propose that the information generated by deep
sequencing of the BBCE cell lines coupled with phenotypic analysis of the mutant
cells can yield mechanistic insights into driver events relevant to human cancer
development.
PMID- 28692055
TI - Cellular prion protein (PrPC) in the development of Merlin-deficient tumours.
AB - Loss of function mutations in the neurofibromatosis Type 2 (NF2) gene, coding for
a tumour suppressor, Merlin, cause multiple tumours of the nervous system such as
schwannomas, meningiomas and ependymomas. These tumours may occur sporadically or
as part of the hereditary condition neurofibromatosis Type 2 (NF2). Current
treatment is confined to (radio) surgery and no targeted drug therapies exist.
NF2 mutations and/or Merlin inactivation are also seen in other cancers including
some mesothelioma, breast cancer, colorectal carcinoma, melanoma and
glioblastoma. To study the relationship between Merlin deficiency and
tumourigenesis, we have developed an in vitro model comprising human primary
schwannoma cells, the most common Merlin-deficient tumour and the hallmark for
NF2. Using this model, we show increased expression of cellular prion protein
(PrPC) in schwannoma cells and tissues. In addition, a strong overexpression of
PrPC is observed in human Merlin-deficient mesothelioma cell line TRA and in
human Merlin-deficient meningiomas. PrPC contributes to increased proliferation,
cell-matrix adhesion and survival in schwannoma cells acting via 37/67 kDa non
integrin laminin receptor (LR/37/67 kDa) and downstream ERK1/2, PI3K/AKT and FAK
signalling pathways. PrPC protein is also strongly released from schwannoma cells
via exosomes and as a free peptide suggesting that it may act in an autocrine
and/or paracrine manner. We suggest that PrPC and its interactor, LR/37/67 kDa,
could be potential therapeutic targets for schwannomas and other Merlin-deficient
tumours.
PMID- 28692056
TI - PDZK1 inhibits the development and progression of renal cell carcinoma by
suppression of SHP-1 phosphorylation.
AB - Renal cell carcinoma (RCC) is one of the most aggressive urologic cancers,
however, the mechanism on supporting RCC carcinogenesis is still not clear. By
using gene expression profile analysis and functional clustering, PDZ domain
containing 1 (PDZK1) was revealed to be downregulated in human clear cell renal
cell carcinoma (ccRCC) samples, which was also verified in several independent
public ccRCC data sets. Using PDZK1 overexpression and knockdown models in ccRCC
cell lines, we demonstrated that PDZK1 inhibited cell proliferation, cell cycle
G1/S phase transition, cell migration and invasion, indicating a tumor-suppressor
role in the development and progression of ccRCC. Our study further demonstrated
that PDZK1 inhibited cell proliferation and migration of ccRCC via targeting SHP
1. PDZK1 was further identified to suppress cell proliferation by blocking SHP-1
phosphorylation at Tyr536 via inhibition of the association between SHP-1 and
PLCbeta3, and then retarding Akt phosphorylation and promoting STAT5
phosphorylation in ccRCC cells. Moreover, the inhibitive effects of PDZK1 on SHP
1 phosphorylation and the tumor growth were verified in vivo by xenograft tumor
studies. Accordingly, PDZK1 expression was negatively correlated with SHP-1
activation and phosphorylation, advanced pathologic stage, tumor weight and size,
and prognosis of ccRCC patients. These findings have provided first lines of
evidences that PDZK1 expression is negatively correlated with SHP-1 activation
and poor clinical outcomes in ccRCC. PDZK1 was identified as a novel tumor
suppressor in ccRCC by negating SHP-1 activity.
PMID- 28692057
TI - The interactome of metabolic enzyme carbonic anhydrase IX reveals novel roles in
tumor cell migration and invadopodia/MMP14-mediated invasion.
AB - Carbonic anhydrase IX (CAIX) is a hypoxia inducible factor 1-induced, cell
surface pH regulating enzyme with an established role in tumor progression and
clinical outcome. However, the molecular basis of CAIX-mediated tumor progression
remains unclear. Here, we have utilized proximity dependent biotinylation (BioID)
to map the CAIX 'interactome' in breast cancer cells in order to identify
physiologically relevant CAIX-associating proteins with potential roles in tumor
progression. High confidence proteins identified include metabolic transporters,
beta1 integrins, integrin-associated protein CD98hc and matrix metalloprotease 14
(MMP14). Biochemical studies validate the association of CAIX with alpha2beta1
integrin, CD98hc and MMP14, and immunofluorescence microscopy demonstrates
colocalization of CAIX with alpha2beta1 integrin and MMP14 in F-actin/cofilin
positive lamellipodia/pseudopodia, and with MMP14 to cortactin/Tks5-positive
invadopodia. Modulation of CAIX expression and activity results in significant
changes in cell migration, collagen degradation and invasion. Mechanistically, we
demonstrate that CAIX associates with MMP14 through potential phosphorylation
residues within its intracellular domain, and that CAIX enhances MMP14-mediated
collagen degradation by directly contributing hydrogen ions required for MMP14
catalytic activity. These findings establish hypoxia-induced CAIX as a novel
metabolic component of cellular migration and invasion structures, and provide
new mechanistic insights into its role in tumor cell biology.
PMID- 28692058
TI - Tumor suppressor Pdcd4 attenuates Sin1 translation to inhibit invasion in colon
carcinoma.
AB - Programmed cell death 4 (Pdcd4), a tumor invasion suppressor, is frequently
downregulated in colorectal cancer and other cancers. In this study, we find that
loss of Pdcd4 increases the activity of mammalian target of rapamycin complex 2
(mTORC2) and thereby upregulates Snail expression. Examining the components of
mTORC2 showed that Pdcd4 knockdown increased the protein but not mRNA level of
stress-activated-protein kinase interacting protein 1 (Sin1), which resulted from
enhanced Sin1 translation. To understand how Pdcd4 regulates Sin1 translation,
the SIN1 5' untranslated region (5'UTR) was fused with luciferase reporter and
named as 5'Sin1-Luc. Pdcd4 knockdown/knockout significantly increased the
translation of 5'Sin1-Luc but not the control luciferase without the SIN1 5'UTR,
suggesting that Sin1 5'UTR is necessary for Pdcd4 to inhibit Sin1 translation.
Ectopic expression of wild-type Pdcd4 and Pdcd4(157-469), a deletion mutant that
binds to translation initiation factor 4A (eIF4A), sufficiently inhibited Sin1
translation, and thus suppressed mTORC2 kinase activity and invasion in colon
tumor cells. By contrast, Pdcd4(157-469)(D253A,D418A), a mutant that does not
bind to eIF4A, failed to inhibit Sin1 translation, and consequently failed to
repress mTORC2 activity and invasion. In addition, directly inhibiting eIF4A with
silvestrol significantly suppressed Sin1 translation and attenuated invasion.
These results indicate that Pdcd4-inhibited Sin1 translation is through
suppressing eIF4A, and functionally important for suppression of mTORC2 activity
and invasion. Moreover, in colorectal cancer tissues, the Sin1 protein but not
mRNA was significantly upregulated while Pdcd4 protein was downregulated,
suggesting that loss of Pdcd4 might correlate with Sin1 protein level but not
mRNA level in colorectal cancer patients. Taken together, our work reveals a
novel mechanism by which Pdcd4 inhibits Sin1 translation to attenuatemTORC2
activity and thereby suppresses invasion.
PMID- 28692059
TI - Air-stable and freestanding lithium alloy/graphene foil as an alternative to
lithium metal anodes.
AB - Developing high-capacity anodes is a must to improve the energy density of
lithium batteries for electric vehicle applications. Alloy anodes are one
promising option, but without pre-stored lithium, the overall energy density is
limited by the low-capacity lithium metal oxide cathodes. Recently, lithium metal
has been revived as a high-capacity anode, but faces several challenges owing to
its high reactivity and uncontrolled dendrite growth. Here, we show a series of
Li-containing foils inheriting the desirable properties of alloy anodes and pure
metal anodes. They consist of densely packed LixM (M = Si, Sn, or Al)
nanoparticles encapsulated by large graphene sheets. With the protection of
graphene sheets, the large and freestanding LixM/graphene foils are stable in
different air conditions. With fully expanded LixSi confined in the highly
conductive and chemically stable graphene matrix, this LixSi/graphene foil
maintains a stable structure and cyclability in half cells (400 cycles with 98%
capacity retention). This foil is also paired with high-capacity Li-free V2O5 and
sulfur cathodes to achieve stable full-cell cycling.
PMID- 28692060
TI - Band-edge engineering for controlled multi-modal nanolasing in plasmonic
superlattices.
AB - Single band-edge states can trap light and function as high-quality optical
feedback for microscale lasers and nanolasers. However, access to more than a
single band-edge mode for nanolasing has not been possible because of limited
cavity designs. Here, we describe how plasmonic superlattices-finite-arrays of
nanoparticles (patches) grouped into microscale arrays-can support multiple band
edge modes capable of multi-modal nanolasing at programmed emission wavelengths
and with large mode spacings. Different lasing modes show distinct input-output
light behaviour and decay dynamics that can be tailored by nanoparticle size. By
modelling the superlattice nanolasers with a four-level gain system and a time
domain approach, we reveal that the accumulation of population inversion at
plasmonic hot spots can be spatially modulated by the diffractive coupling order
of the patches. Moreover, we show that symmetry-broken superlattices can sustain
switchable nanolasing between a single mode and multiple modes.
PMID- 28692061
TI - A causal account of the brain network computations underlying strategic social
behavior.
AB - During competitive interactions, humans have to estimate the impact of their own
actions on their opponent's strategy. Here we provide evidence that neural
computations in the right temporoparietal junction (rTPJ) and interconnected
structures are causally involved in this process. By combining inhibitory
continuous theta-burst transcranial magnetic stimulation with model-based
functional MRI, we show that disrupting neural excitability in the rTPJ reduces
behavioral and neural indices of mentalizing-related computations, as well as
functional connectivity of the rTPJ with ventral and dorsal parts of the medial
prefrontal cortex. These results provide a causal demonstration that neural
computations instantiated in the rTPJ are neurobiological prerequisites for the
ability to integrate opponent beliefs into strategic choice, through system-level
interaction within the valuation and mentalizing networks.
PMID- 28692062
TI - Neural reactivations during sleep determine network credit assignment.
AB - A fundamental goal of motor learning is to establish the neural patterns that
produce a desired behavioral outcome. It remains unclear how and when the nervous
system solves this 'credit assignment' problem. Using neuroprosthetic learning,
in which we could control the causal relationship between neurons and behavior,
we found that sleep-dependent processing was required for credit assignment and
the establishment of task-related functional connectivity reflecting the casual
neuron-behavior relationship. Notably, we observed a strong link between the
microstructure of sleep reactivations and credit assignment, with downscaling of
non-causal activity. Decoupling of spiking to slow oscillations using optogenetic
methods eliminated rescaling. Thus, our results suggest that coordinated firing
during sleep is essential for establishing sparse activation patterns that
reflect the causal neuron-behavior relationship.
PMID- 28692063
TI - Inflammation-dependent cerebrospinal fluid hypersecretion by the choroid plexus
epithelium in posthemorrhagic hydrocephalus.
AB - The choroid plexus epithelium (CPE) secretes higher volumes of fluid
(cerebrospinal fluid, CSF) than any other epithelium and simultaneously functions
as the blood-CSF barrier to gate immune cell entry into the central nervous
system. Posthemorrhagic hydrocephalus (PHH), an expansion of the cerebral
ventricles due to CSF accumulation following intraventricular hemorrhage (IVH),
is a common disease usually treated by suboptimal CSF shunting techniques. PHH is
classically attributed to primary impairments in CSF reabsorption, but little
experimental evidence supports this concept. In contrast, the potential
contribution of CSF secretion to PHH has received little attention. In a rat
model of PHH, we demonstrate that IVH causes a Toll-like receptor 4 (TLR4)- and
NF-kappaB-dependent inflammatory response in the CPE that is associated with a ~3
fold increase in bumetanide-sensitive CSF secretion. IVH-induced hypersecretion
of CSF is mediated by TLR4-dependent activation of the Ste20-type stress kinase
SPAK, which binds, phosphorylates, and stimulates the NKCC1 co-transporter at the
CPE apical membrane. Genetic depletion of TLR4 or SPAK normalizes hyperactive CSF
secretion rates and reduces PHH symptoms, as does treatment with drugs that
antagonize TLR4-NF-kappaB signaling or the SPAK-NKCC1 co-transporter complex.
These data uncover a previously unrecognized contribution of CSF hypersecretion
to the pathogenesis of PHH, demonstrate a new role for TLRs in regulation of the
internal brain milieu, and identify a kinase-regulated mechanism of CSF secretion
that could be targeted by repurposed US Food and Drug Administration (FDA)
approved drugs to treat hydrocephalus.
PMID- 28692064
TI - Plk1 regulates contraction of postmitotic smooth muscle cells and is required for
vascular homeostasis.
AB - Polo-like kinase 1 (PLK1), an essential regulator of cell division, is currently
undergoing clinical evaluation as a target for cancer therapy. We report an
unexpected function of Plk1 in sustaining cardiovascular homeostasis. Plk1
haploinsufficiency in mice did not induce obvious cell proliferation defects but
did result in arterial structural alterations, which frequently led to aortic
rupture and death. Specific ablation of Plk1 in vascular smooth muscle cells
(VSMCs) led to reduced arterial elasticity, hypotension, and an impaired arterial
response to angiotensin II in vivo. Mechanistically, we found that Plk1 regulated
angiotensin II-dependent activation of RhoA and actomyosin dynamics in VSMCs in a
mitosis-independent manner. This regulation depended on Plk1 kinase activity, and
the administration of small-molecule Plk1 inhibitors to angiotensin II-treated
mice led to reduced arterial fitness and an elevated risk of aneurysm and aortic
rupture. We thus conclude that a partial reduction of Plk1 activity that does not
block cell division can nevertheless impair aortic homeostasis. Our findings have
potentially important implications for current approaches aimed at PLK1
inhibition for cancer therapy.
PMID- 28692065
TI - Increased cathepsin S in Prdm1-/- dendritic cells alters the TFH cell repertoire
and contributes to lupus.
AB - Aberrant population expansion of follicular helper T cells (TFH cells) occurs in
patients with lupus. An unanswered question is whether an altered repertoire of T
cell antigen receptors (TCRs) is associated with such expansion. Here we found
that the transcription factor Blimp-1 (encoded by Prdm1) repressed expression of
the gene encoding cathepsin S (Ctss), a cysteine protease that cleaves invariant
chains and produces antigenic peptides for loading onto major histocompatibility
complex (MHC) class II molecules. The increased CTSS expression in dendritic
cells (DCs) from female mice with dendritic cell-specific conditional knockout of
Prdm1 (CKO mice) altered the presentation of antigen to CD4+ T cells. Analysis of
complementarity-determining region 3 (CDR3) regions containing the beta-chain
variable region (Vbeta) demonstrated a more diverse repertoire of TFH cells from
female CKO mice than of those from wild-type mice. In vivo treatment of CKO mice
with a CTSS inhibitor abolished the lupus-related phenotype and reduced the
diversity of the TFH cell TCR repertoire. Thus, Blimp-1 deficiency in DCs led to
loss of appropriate regulation of Ctss expression in female mice and thereby
modulated antigen presentation and the TFH cell repertoire to contribute to
autoimmunity.
PMID- 28692066
TI - Genotype-covariate interaction effects and the heritability of adult body mass
index.
AB - Obesity is a worldwide epidemic, with major health and economic costs. Here we
estimate heritability for body mass index (BMI) in 172,000 sibling pairs and
150,832 unrelated individuals and explore the contribution of genotype-covariate
interaction effects at common SNP loci. We find evidence for genotype-age
interaction (likelihood ratio test (LRT) = 73.58, degrees of freedom (df) = 1, P
= 4.83 * 10-18), which contributed 8.1% (1.4% s.e.) to BMI variation. Across
eight self-reported lifestyle factors, including diet and exercise, we find
genotype-environment interaction only for smoking behavior (LRT = 19.70, P = 5.03
* 10-5 and LRT = 30.80, P = 1.42 * 10-8), which contributed 4.0% (0.8% s.e.) to
BMI variation. Bayesian association analysis suggests that BMI is highly
polygenic, with 75% of the SNP heritability attributable to loci that each
explain <0.01% of the phenotypic variance. Our findings imply that substantially
larger sample sizes across ages and lifestyles are required to understand the
full genetic architecture of BMI.
PMID- 28692067
TI - Synchronized DNA cycling across a bacterial population.
AB - A defining goal of synthetic biology is to engineer cells to coordinate tasks
that often require precise temporal modulation of gene expression. Although a
variety of relatively small gene circuits have been constructed and
characterized, their logical combination into larger networks remains a central
challenge. This is due primarily to the lack of compatible and orthogonal
elements for predictable dynamic control of gene expression. As an alternative
approach to promoter-level regulation, we explored the use of DNA copy number as
a circuit control element. We engineered colony-wide DNA cycling in Escherichia
coli in the form of plasmid copy number oscillations via a modular design that
can be readily adapted for use with other gene circuitry. Copy number modulation
is a generalizable principle that adds a layer of control to synthetic gene
circuits, allowing dynamic regulation of circuit elements without requiring
specially engineered promoters.
PMID- 28692068
TI - Allosteric sensitization of proapoptotic BAX.
AB - BCL-2-associated X protein (BAX) is a critical apoptotic regulator that can be
transformed from a cytosolic monomer into a lethal mitochondrial oligomer, yet
drug strategies to modulate it are underdeveloped due to longstanding
difficulties in conducting screens on this aggregation-prone protein. Here, we
overcame prior challenges and performed an NMR-based fragment screen of full
length human BAX. We identified a compound that sensitizes BAX activation by
binding to a pocket formed by the junction of the alpha3-alpha4 and alpha5-alpha6
hairpins. Biochemical and structural analyses revealed that the molecule
sensitizes BAX by allosterically mobilizing the alpha1-alpha2 loop and BAX BH3
helix, two motifs implicated in the activation and oligomerization of BAX,
respectively. By engaging a region of core hydrophobic interactions that
otherwise preserve the BAX inactive state, the identified compound reveals
fundamental mechanisms for conformational regulation of BAX and provides a new
opportunity to reduce the apoptotic threshold for potential therapeutic benefit.
PMID- 28692069
TI - The structure of vanadium nitrogenase reveals an unusual bridging ligand.
AB - Nitrogenases catalyze the reduction of dinitrogen (N2) gas to ammonium at a
complex heterometallic cofactor. This most commonly occurs at the FeMo cofactor
(FeMoco), a [Mo-7Fe-9S-C] cluster whose exact reactivity and substrate-binding
mode remain unknown. Alternative nitrogenases replace molybdenum with either
vanadium or iron and differ in reactivity, most prominently in the ability of
vanadium nitrogenase to reduce CO to hydrocarbons. Here we report the 1.35-A
structure of vanadium nitrogenase from Azotobacter vinelandii. The 240-kDa
protein contains an additional alpha-helical subunit that is not present in
molybdenum nitrogenase. The FeV cofactor (FeVco) is a [V-7Fe-8S-C] cluster with a
homocitrate ligand to vanadium. Unexpectedly, it lacks one sulfide ion compared
to FeMoco, which is replaced by a bridging ligand, likely a MU-1,3-carbonate. The
anion fits into a pocket within the protein that is obstructed in molybdenum
nitrogenase, and its different chemical character helps to rationalize the
altered chemical properties of this unique N2- and CO-fixing enzyme.
PMID- 28692070
TI - [The draft of the ICD-11 chapter on mental and behavioral disorders: an update
for clinicians].
AB - The ICD-11 chapter on mental and behavioral disorders is currently under
development. A simplified version of the diagnostic guidelines for schizophrenia
and other primary psychotic disorders, mood disorders, anxiety disorders,
disorders specifically associated with stress, and feeding and eating disorders
has been made available for use in the field studies. For all the other sections
of the classification, a brief general definition and sometimes a description of
some of the included disorders can be found on the ICD-11 beta platform. In the
present article, we provide some information on the content of the various
sections of the classification on the basis of the available documents, with the
warning that some of the aspects may still be subject to revision.
PMID- 28692071
TI - [Charges and convictions of psychiatrists for the violent behavior of the
patient: psychiatric-forensic remarks].
AB - Purpose of the present study is to point-out a number of psychiatric-forensic
remarks about the management of violent behavior against the person (VBP) amongst
psychiatric patients. The study is the authors' personal contribution based on
clinical and forensic experience as experts in the management of psychiatric
patients with VBP. Twelve psychiatric-forensic remarks have been highlighted in
the present study: 1) VBP is a multifactorial event; 2) the risk of VBP against
the person may change rapidly over time in quantity and quality; 3) there are no
methods for reliable prediction of VBP in a single clinical-case; 4) there are no
medications with an indication of "heal" the VBP; 5) there are no therapeutic
measures that neutralize always, quickly and without recurrences VBP; 6) there
exist clinical hypotheses to assess VBP; 7) there exist principles of victimology
to assess VBP; 8) there are emotional reactions that can affect the evaluation
and clinical and forensic management of VBP; 9) the responsibility of the
psychiatrist has to be evaluated at the moment of the events; 10) the
responsibility of the psychiatrist must be contextualized in the single clinical
case; 11) there is the need to clarify the individual professional responsibility
of psychiatrists who treated a patient; 12) there is the need to clarify the
criteria for the definition of the guarantee role. The above-mentioned twelve
psychiatric-forensic remarks have implications in the assessment and management
of psychiatric patients with violent behavior. They may constitute a basis for
further discussion aiming to obtain consensus amongst psychiatrists about good
clinical practice and forensic implication in the management of psychiatric
patients with VBP and to avoid charges and convictions.
PMID- 28692072
TI - Psychotherapy and psychological time: a case study.
AB - AIM: The present study is a comparative case study as part of research on the
psychotherapeutic process. This research describes the perception of subjective
time in two psychotherapeutic processes, one successful and one unsuccessful.
METHODS: We studied two psychotherapeutic processes of cognitive orientation,
which were video recorded and fully transcribed in each session. First a
qualitative analysis was applied for quality coding (Top-down) was performed to
identify category types of subjective time, depending on psychological well
being. These were categorized as past, present, and future; each one in positive
and negative forms. Secondly, two quantitative statistical analyses were applied:
one of content analysis, which allowed us to observe the frequencies for the six
categories, and another, a cumulative frequency analysis, which allowed us to
identify a differential pattern in the analyzed cases. RESULTS: These data showed
different temporal profiles for both cases, differentiated by categories. This
finding that would allow us to track the process of subjectivity in terms of
specific components associated with psychotherapy success. DISCUSSION AND
CONCLUSIONS: We present a mixed method, a qualitative for initial coding of
patient speaking turns and a quantitative methodology such as the cumulative
frequency analysis in time in a therapeutic context. Those changes are
progressive and must be observed as a continuous and dynamic evolution to allow
for an interpretation in a naturalistic context.
PMID- 28692073
TI - Harmony of transitions in Assessing Interpersonal Motivations in Transcripts
analysis can discriminate between Adult Attachment Interview secure and
disorganized individuals.
AB - AIM: Assessing Interpersonal Motivations in Transcripts (AIMIT) is a validated
coding system to assess the activation of interpersonal motivational systems
(IMS) in the transcripts of psychotherapy sessions. The Transition Index (TI) is
an AIMIT measure that reflects the levels of organisation, synchronisation and
harmony amongst two or more IMS when they are rapidly shifting or simultaneously
in the clinical dialogue. It is supposed to be a measure of integration and
coherence of the patient's state of mind within the psychotherapeutic sessions.
It has also been hypothesized that low TI could be a marker for disorganization
of attachment of the patient leading to difficulties in the therapeutic
relationships and ruptures in the therapeutic alliance. In order to assess this
hypothesis we tested its capability to discriminate between Adult Attachment
Interview (AAI) organized and disorganized individuals. METHODS: Two groups of 15
transcriptions of AAI matched for age and sex, one classified as free-autonomous
and one as disorganized, were analysed by the AIMIT method. RESULTS: Compared to
organized individuals, disorganized patients at AAI reported lower TI scores
(3.7+/-0.63 vs 3.0+/-0.53; F=2.98, p=0.005). Furthermore, TI showed a good
discriminant capability (Wilks' Lambda=0.77, p=0.004). DISCUSSION AND CONCLUSION:
This result seems to confirm the usefulness and reliability of AIMIT analysis in
evaluating the interpersonal difficulties which often characterize the
therapeutic relationship with disorganized attachment patients.
PMID- 28692074
TI - First World War and Mental Health: a retrospective comparative study of veterans
admitted to a psychiatric hospital between 1915 and 1918.
AB - AIM: The association between mental illness and war has been repeatedly
investigated. Higher levels of depressive symptoms and an increased suicidal risk
have been found in veterans. In this study we investigated the mental health
conditions among Italian soldiers during the "Great War", who were hospitalized
in a mental health hospital in Italy. METHODS: The study sample consists of 498
soldiers who were admitted during the World War I between 1915 and 1918, and 498
civilian patients admitted in two different periods (1898-1914, 1919-1932).
Psychiatric diagnoses have been recorded retrospectively by a detailed
examination of clinical records. Socio-demographic informations, diagnosis at
first admission, number of admissions, and deployment in war zones were
collected. A logistic regression analysis was performed, the diagnosis of
depression was considered as dependent variable while clinical and demographic
variables as independent predictors. RESULTS: Soldiers deployed in war zones were
more likely to have a diagnosis of depression compared to those not serving on
the frontline. The logistic regression analysis showed that the diagnosis of
depression is predicted by being a soldier and being deployed in a war area.
DISCUSSION AND CONCLUSIONS: Our data confirm that soldiers engaged in war are at
higher risk of developing depression compared to non-deployed soldiers.
PMID- 28692075
TI - Late onset clozapine-induced sierositis: the case of ms C.
AB - INTRODUCTION: Polisierositis is a rare but not negligible adverse event of a
therapy with clozapine, that occurs usually during the titration phase of
clozapine or just after the reachment of the plateau, and politherapy increases
the incidence rate. CASE REPORT: Ms. C. is a 42 years old smoker woman who
suffers from a schizophrenia associated to a borderline personality disorder. In
2007 a therapy with clozapine was introduced with good tolerance and efficacy on
her symptoms for a long period. In August 2015, after a period characterized by
many psychiatric ward admissions an augmentation with valproic acid and
sertraline was done, with partial symptoms improvement. In June 2016, she
developed pleuritis and pericarditis and underwent pleural and pericardial
drainage. After clozapine interruption (andzuclopentixol titration) the symptoms
progressively decreased and in August 2016 she had a complete remission.
CONCLUSIONS: Even if uncommon, sierositis should be taken into consideration also
in long term clozapine treatment, especially when associated with other drugs, as
valproate or sertraline, although the role of the latter is less clear. Moreover,
patients life habits (smoke), allergic or rheumatological disorders or temporary
intake of other drugs (like antifungins) should be recorded carefully for their
possible effects on cytochrome P450 substrates.
PMID- 28692076
TI - [Full functional recovery in depression treatment. Clinical cases treated with
vortioxetina].
AB - Depression is one of the most common diseases worldwide, with more than 350
million people affected. Although many patients initially show a good response to
antidepressant therapy, they tend to suffer from residual symptoms that affect
their social, cognitive, physical and psychological domains. Residual symptoms
severely impact the patient's global functioning and quality of life and increase
the risk of recurrence. In the last few years, pharmacological research has
focused on drugs able to mitigate the severity of depressive symptoms and to
control persistent cognitive and functional disabilities. A novel antidepressant,
with a multimodal mechanism of action that combines the classical inhibition of
serotonin transporter (SERT) with the modulation of serotonin receptor activity,
is vortioxetine. Its efficacy in the treatment of depression and cognitive
symptoms has been well established in numerous randomized clinical trials. Three
cases of patients with depressive disorders are presented, in which vortioxetine
treatment improved depressive symptoms, cognitive symptoms and overall patient
functioning. These anecdotal experiences suggest that vortioxetine, in addition
to controlling all symptoms of depression, including cognitive symptoms, provides
functional benefits in patients with depressive disorders.
PMID- 28692078
TI - Modeling of alcohol oxidase enzyme of Candida boidinii and in silico analysis of
competitive binding of proton ionophores and FAD with enzyme.
AB - Alcohol oxidase (AOX) is an important flavin adenine dinucleotide (FAD) dependent
oxidoreductase, which is responsible for converting methanol into formaldehyde
and hydrogen peroxide for the growth of methylotrophic yeast Candida boidinii.
Although AOX plays a crucial role in methanol catabolism, the experimental
structure of AOX from Candida boidinii has not been elucidated. This study
reports the first complete in silico model of AOX from C. boidinii. This paper
also reports the AOX structure modeled using the threading approach, followed by
structure analysis and molecular dynamics simulation. The modeled structure was
compared with the aryl alcohol oxidase structure (a glucose-methanol-choline
family member, pdbID: 3fim). A docking study was performed to analyze the
interaction between AOX and its cofactor FAD. The AOX modeled structure also
exhibited high similarity with respect to the FAD binding sites, which are the
substrate binding sites as seen with 3fim. It was observed that the adenosine
part of FAD was deeply buried inside AOX while the isoalloxazine ring stuck to
the surface. This paper reports the interaction of selective proton ionophores
(CCCP and DNP) with AOX and also reports their binding sites. These proton
ionophores showed competitive binding with FAD. The occupancy of the FAD binding
sites by the proton ionophore may lead to blocking of the entry of FAD and
thereby disruption of AOX import into peroxisomes.
PMID- 28692080
TI - Aromaticity and antiaromaticity of substituted fulvene derivatives: perspectives
from the information-theoretic approach in density functional reactivity theory.
AB - Even though the concept of aromaticity and antiaromaticity is extremely important
and widely used, there still exist lots of controversies in the literature, which
are believed to be originated from the fact that there are so many aromatic types
discovered and at the same time there are many aromaticity indexes proposed. In
this work, using seven series of substituted fulvene derivatives as an example
and with the information-theoretic approach in density functional reactivity
theory, we examine these concepts from a different perspective. We investigate
the changing patterns of Shannon entropy, Fisher information, Ghosh-Berkowitz
Parr entropy, information gain, Onicescu information energy, and relative Renyi
entropy on the ring carbon atoms of these systems. Meanwhile, we also consider
variation trends of four representative kinds of aromaticity indexes such as FLU,
HOMA, ASE and NICS. Statistical analyses among these quantities show that with
the same ring structure of the derivatives, both information-theoretic quantities
and aromaticity indexes obey the same changing pattern, which are valid across
all seven systems studied. However, cross correlations between these two sets of
quantities yield two completely opposite patterns. These ring-structure dependent
correlations are in good agreement with Huckel's 4n + 2 rule of aromaticity and
4n rule of antiaromaticity. Our results should provide a novel and complementary
viewpoint on how aromaticity and antiaromaticity should be appreciated and
categorized. More studies are in progress to further our understanding about the
matter.
PMID- 28692081
TI - Motion-induced change in emission (MICE) for developing fluorescent probes.
AB - The need for detecting and labelling environmentally and biologically important
analytes has driven considerable research efforts in developing fluorescent
probes. During the sensing process, molecular motions (i.e., molecular rotations
or vibrations) of a flexible fluorescent probe can be significantly altered by
its embedding micro-environment or analyte, thereby leading to substantial
changes in readout signals. Motion-induced change in emission (MICE) can be
utilized as an effective sensing mechanism. However, in comparison to the well
understood sensing mechanisms, such as photo-induced electron transfer (PET),
intramolecular charge transfer (ICT), aggregation-induced emission (AIE) and
disaggregation-induced emission (DIE), MICE has not been systematically discussed
to date. In this tutorial review, we will summarize the concept and mechanisms of
MICE for developing single-molecular fluorescent probes, present unique
advantages of MICE based sensors, demonstrate their various applications, and
discuss technical challenges in this field. We expect that this review will
promote a deeper understanding of MICE and facilitate the development of novel
MICE based probes.
PMID- 28692082
TI - Effect of physisorption of inert organic molecules on Au(111) surface electronic
states.
AB - The modification of the Au(111) Shockley surface state (SS) by an n-alkane
molecule (n-tetratetracontane) monolayer was observed by angle-resolved
ultraviolet photoemission spectroscopy. Although there is little chance of
chemical interaction in this ideal physisorption system, the volume of the Fermi
surface of the SS was significantly reduced accompanied by the formation of large
interface electric dipoles. Moreover, Rashba splitting of the SS by spin-orbit
interactions was slightly increased upon n-tetratetracontane adsorption, which
arose from the decrease in the symmetry of the wave function around the Au nuclei
at the surface. The detailed information about the simple physisorption system
presented in this paper provides basic knowledge for understanding the electronic
structure at the interface between other organic molecules and metal substrates.
PMID- 28692084
TI - Designing effective 'frustrated Lewis pair' hydrogenation catalysts.
AB - The past decade has seen the subject of transition metal-free catalytic
hydrogenation develop incredibly rapidly, transforming from a largely
hypothetical possibility to a well-established field that can be applied to the
reduction of a diverse variety of functional groups under mild conditions. This
remarkable change is principally attributable to the development of so-called
'frustrated Lewis pairs': unquenched combinations of bulky Lewis acids and bases
whose dual reactivity can be exploited for the facile activation of otherwise
inert chemical bonds. While a number of comprehensive reviews into frustrated
Lewis pair chemistry have been published in recent years, this tutorial review
aims to provide a focused guide to the development of efficient FLP hydrogenation
catalysts, through identification and consideration of the key factors that
govern their effectiveness. Following discussion of these factors, their
importance will be illustrated using a case study from our own research, namely
the development of FLP protocols for successful hydrogenation of aldehydes and
ketones, and for related moisture-tolerant hydrogenation.
PMID- 28692085
TI - Functional roles of intrinsic disorder in CRISPR-associated protein Cas9.
AB - Protein intrinsic disorder is an important characteristic commonly detected in
multifunctional or RNA- and DNA-binding proteins. Due to their high
conformational flexibility and solvent accessibility, intrinsically disordered
proteins (IDPs) and IDP regions (IDPRs) execute diverse functions including
interaction with multiple partners, and are frequently subjected to various post
translational modifications. Recent studies on the components comprising the
CRISPR (clustered regularly interspaced short palindromic repeats) system have
elucidated the crystal structure of Cas9 proteins and the mechanism by which the
Cas9-sgRNA complex recognizes and cleaves its target DNA. Yet the extent and
functional implications of intrinsic disorder in the Cas9 protein have never been
fully assessed. Here, we present a comprehensive computational analysis based on
both sequence and structural data in an attempt to investigate the roles of IDPRs
in the functioning of Cas9 proteins of different origin. We conclude that among
the functional roles of IDPRs in Cas9 proteins are recognition of the target DNA
and mediation of nucleic acid and protein binding.
PMID- 28692083
TI - Using biomaterials to rewire the process of wound repair.
AB - Wound healing is one of the most complex processes that our bodies must perform.
While our ability to repair wounds is often taken for granted, conditions such as
diabetes, obesity, or simply old age can significantly impair this process. With
the incidence of all three predicted to continue growing into the foreseeable
future, there is an increasing push to develop strategies that facilitate
healing. Biomaterials are an attractive approach for modulating all aspects of
repair, and have the potential to steer the healing process towards regeneration.
In this review, we will cover recent advances in developing biomaterials that
actively modulate the process of wound healing, and will provide insight into how
biomaterials can be used to simultaneously rewire multiple phases of the repair
process.
PMID- 28692086
TI - The role of O(1D) in the oxidation mechanism of ethylene by iodosobenzene and
other hypervalent molecules.
AB - The role of the first excited state of oxygen (1D) is proven essential for the
description of terminal iodine-oxygen chemical bonds. The description of the I-O
bond as a dative one from iodine to O(1D) provides a simple and accurate picture
which explains the oxidation properties of iodosobenzene and similar in nature
molecules.
PMID- 28692087
TI - Ionic liquids with thioether motifs as synthetic cationic lipids for gene
delivery.
AB - This study introduces a novel class of imidazolium- and ammonium-based ionic
liquids possessing two C12 and C14 tails and thioether linkers designed for
lipoplex-mediated DNA delivery. Imidazolium-based ionic liquids displayed
efficient gene delivery properties with low toxicity. Thiol-yne click chemistry
was employed for the facile and robust synthesis of these thioether-based
cationic lipioids with enhanced lipophilicity and low fluidity.
PMID- 28692088
TI - The influence of coordination modes and active sites of a 5-(triazol-1-yl)
nicotinic ligand on the assembly of diverse MOFs.
AB - Six new complexes based on 5-(triazol-1-yl)nicotinic acid (HL), namely
[Cu2(L)3(H2O)(OH)]n (1), [Co(L)2(H2O)2]n (2), [Mn(L)2(H2O)2]n (3),
{[Co(L)(H2O)0.5(DMF)0.5(NO3)0.5].(Cl)0.5.DMF.2H2O}n (4),
{[Cu(L)(O)0.5].CH3OH.2.5H2O}n (5) and {[Co2(L)4(H2O)].2DMA.2H2O}n (6), were
synthesized under hydro(solvo)thermal conditions. The L- ligand in 1-6 reveals
various coordination modes and forms diverse secondary building units (SBUs) in
the final structures. Complex 1 shows a 2D layered structure with a rare (3,8)
connected topology based on tetranuclear [Cu4(COO)6(H2O)2(OH)2N6] SBUs. 2 and 3
are isostructural and display 2D 4-connected sql nets with a point symbol of
(44.62). 4 and 5 have similar spatial 3D porous frameworks, which can be
simplified as a (3,6)-connected 2-nodal net via dinuclear
[Co2(COO)2(O)2(NO3)(N)4] SBUs and [Cu2(COO)2(O)(N)4] SBUs, respectively. 6 is a
3D porous framework constructed by dinuclear [Co2(COO)4(H2O)(N)4] motifs with a
uninodal 4-connected qtz net. The magnetic properties and gas sorption behaviour
of these complexes were investigated carefully, showing that 3 exhibits
ferrimagnetic character and 4 demonstrates its effective storage capacity for CO2
as well as high selectivity for CO2 over CH4 under ambient conditions.
PMID- 28692089
TI - Non-activation MOF arrays as a coating layer to fabricate a stable
superhydrophobic micro/nano flower-like architecture.
AB - Non-activation metal-organic framework (MOF) arrays are directly applied as a
coating layer to fabricate a stable superhydrophobic micro/nano flower-like
architecture. The MOF functionalized surfaces can be synthesized easily on
different substrates without any activation procedure or modification by low free
energy materials, which exhibit attractive performance in oil/water separation.
PMID- 28692090
TI - The effect of an external magnetic field on the dealloying process of the Ni-Al
alloy in alkaline solution.
AB - Our work investigates the effect of an external magnetic field on different
dealloying stages of the formation of a nanoporous magnetic material. The
magnetic field first prolongs the Ni rearrangement process at a low magnetic flux
density, whereas the trend is reversed and the Ni rearrangement process is
shortened at a higher magnetic flux density. The much finer morphology of
nanoporous Ni can be prepared by adjusting the external magnetic flux density.
PMID- 28692091
TI - Coherent intermolecular proton transfer in the acid-base reaction of excited
state pyranine.
AB - Detailed molecular dynamics simulations of an acid-base reaction have been the
subject of extensive investigations. Here we report the excited state proton
transfer dynamics of pyranine (8-hydroxypyrene-1,3,6-trisulfonic acid, HPTS) in
acetate buffer by time-resolved fluorescence (TF) and quantum
mechanical/effective fragment potential molecular dynamics (QM/EFP-MD)
simulations. High time resolution in TF and TF spectra measurements allows the
acquisition of accurate reaction kinetics. Upon the photoexcitation of HPTS, the
proton (deuterium) is transferred coherently to acetate in 60 fs (80 fs) for a
contact pair of HPTS (DPTS) and acetate by a hydrogen bond, which comprises
approximately 28% of the population. ESPT proceeds slowly on a picosecond time
scale for the remaining HPTS as reported previously. Coherent wave packet motions
of the reactant (acid) and the product (conjugate base) enable the acquisition of
the vibrational spectra of excited states via TF (VETF). A comparison of the
VETFs of the reactant and the product and the calculation of the Huang-Rhys
factors (vibrational reorganization energies) identify the vibrational modes that
actively participate in the coherent proton transfer. In particular, the 246 cm-1
vibrational mode, which consists of in-plane skeletal stretching motion, promotes
the ESPT by transferring the donor oxygen towards the acceptor oxygen in acetate.
QM/EFP MD simulations corroborate the experiment and provide molecular details of
the ESPT.
PMID- 28692092
TI - Photodissociation of CH3CHO at 248 nm: identification of the channels of roaming,
triple fragmentation and the transition state.
AB - Quasi-classical trajectory (QCT) calculations are performed on the molecular
products CO + CH4via the tight transition state (TS) and global minimum
configurations. With the aid of this theoretical evidence, we have re-examined
the experimental results published previously to clarify the controversial issue
of photodissociation dynamics of CH3CHO at 248 nm. For the CO (v = 0 and 1)
bimodal rotational distributions obtained previously [K.-C. Hung, P.-Y. Tsai, H.
K. Li, and K.-C. Lin, J. Chem. Phys., 2014, 140, 064313], the low-rotational (J)
component is re-assigned to the contribution of triple fragmentation (H + CO +
CH3), whereas the high-J component is ascribed to the CH3-roaming pathway. The H
roaming pathway is not found in the calculations. Further, the QCT results have
confirmed that the CO vibrational population especially at higher states and the
low-energy component of CH4 vibrational bimodality obtained experimentally are
mainly produced following the TS pathway, which has never been identified before.
While taking into account both the theoretical and experimental results, the
ratio of the molecular products (CO(v = 1) + CH4) obtained by the triple
fragmentation/roaming/TS processes is evaluated to be 0.23 : 1 : 0.29.
PMID- 28692093
TI - Chemoselective ligation reaction of N-acetylglucosamine (NAG) with hydrazide
functional probes to determine galactosyltransferase activity by MALDI mass
spectrometry.
AB - Quantification of beta-1,4-galactosyltransferase (beta-1,4-GT) activity is of
considerable significance in the diagnosis of various cancers including lung and
ovarian cancer. We report here the use of synthetic beta-N-acetylglucosamine
(NAG) ligands that contain hydrazide functional groups to determine
galactosyltransferase activity by mass spectrometry. With hydrazide-linked beta-d
NAG as the acceptor, the activity of beta-1,4-GT is quantified by matrix-assisted
laser desorption/ionization (MALDI)-time-of-flight (TOF) mass spectrometry (MS)
with high efficiency. Using the disulfide moiety in a 3,3'-dithiodipropionic acid
dihydrazide (DTP)-linked beta-d-NAG probe, Au nanoparticles (AuNPs) are employed
for enriching DTP-linked beta-d-NAG after enzymatic reaction, and the ligand
bound AuNPs are subsequently deposited on a MALDI plate for analysis. In
addition, we have demonstrated that a perfluorocarbon (PF) labeled beta-NAG
ligand can be useful for surface-based enzymatic reaction with a
perfluorooctadecanethiol (PFDT)-covered gold surface. Using the ratiometric
method, the conversion rate of beta-1,4-GT is determined to be 0.83 +/- 0.03,
which shows a high level of activity. This is the first work that uses hydrazide
linked beta-d-NAG for activity analysis, providing a new surface-based MS
approach to determine enzyme activity in a potentially high-throughput manner.
PMID- 28692094
TI - Multi-functionalized herringbone carbon nanofiber for anodes of lithium ion
batteries.
AB - Herringbone carbon nanofibers (HCNFs) are prepared for use as anode materials in
lithium-ion batteries (LIBs). HCNFs are prepared using a Ni-Fe catalyst and
subsequently multi-functionalized with oxygen using the Hummers' method, and then
with both oxygen and nitrogen-containing 2-ureido-4[1H]pyrimidinone (UHP)
moieties, which endow the HCNFs with the ability to form quadruple hydrogen bonds
(QHBs). The as-prepared HCNFs are, on average, 13 MUm in length and 100 nm in
diameter, with a highly graphitic structure. The oxidized HCNFs (Ox-HCNFs)
obtained by Hummers' method are partially exfoliated, having double-bladed saw
like structures that extend in the direction of the graphite planes. QHBs are
formed between the HCNFs after functionalization with the UHP moieties. The final
surface-modified HCNFs (N-Ox-HCNFs) have more electrochemical sites, shorter Li+
diffusion lengths, and additional electron pathways compared with the as-prepared
HCNF and Ox-HCNF. The introduction of oxygen- and nitrogen-containing functional
groups improves the performance of LIBs: a high charge capacity of 763 mA h g-1
at 0.1 A g-1, excellent rate capability (a capacity of 402 mA h g-1 at 3 A g-1),
and near 100% capacity retention after 300 cycles are reported.
PMID- 28692096
TI - A quantum-rovibrational-state-selected study of the proton-transfer reaction
H2+(X2Sigma: v+ = 1-3; N+ = 0-3) + Ne -> NeH+ + H using the pulsed field
ionization-photoion method: observation of the rotational effect near the
reaction threshold.
AB - Using the sequential electric field pulsing scheme for vacuum ultraviolet (VUV)
laser pulsed field ionization-photoion (PFI-PI) detection, we have successfully
prepared H2+(X2Sigma: v+ = 1-3; N+ = 0-5) ions in the form of an ion beam in
single quantum-rovibrational-states with high purity, high intensity, and narrow
laboratory kinetic energy spread (DeltaElab ~ 0.05 eV). This VUV-PFI-PI ion
source, when coupled with the double-quadrupole double-octupole ion-molecule
reaction apparatus, has made possible a systematic examination of the vibrational
as well as rotational-state effects on the proton transfer reaction of
H2+(X2Sigma: v+; N+) + Ne. Here, we present the integral cross sections
[sigma(v+; N+)'s] for the H2+(v+ = 1-3; N+ = 0-3) + Ne -> NeH+ + H reaction
observed in the center-of-mass kinetic energy (Ecm) range of 0.05-2.00 eV. The
sigma(v+ = 1, N+ = 1) exhibits a distinct Ecm onset, which is found to agree with
the endothermicity of 0.27 eV for the proton transfer process after taking into
account of experimental uncertainties. Strong v+-vibrational enhancements are
observed for sigma(v+ = 1-3, N+) in the Ecm range of 0.05-2.00 eV. While
rotational excitations appear to have little effect on sigma(v+ = 3, N+), a
careful search leads to the observation of moderate N+-rotational enhancements at
v+ = 2: sigma(v+ = 2; N+ = 0) < sigma(v+ = 2; N+ = 1) < sigma(v+ = 2; N+ = 2) <
sigma(v+ = 2; N+ = 3), where the formation of NeH+ is near thermal-neutral. The
sigma(v+ = 1-3, N+ = 0-3) values obtained here are compared with previous
experimental results and the most recent state-of-the-art quantum dynamics
predictions. We hope that these new experimental results would further motivate
more rigorous theoretical calculations on the dynamics of this prototypical ion
molecule reaction.
PMID- 28692097
TI - Controlling the enthalpy-entropy competition in supramolecular fullerene liquid
crystals by tuning the flexible chain length.
AB - We present here that in two-dimensional (2D) fullerene supramolecular liquid
crystals (SLCs), the phase diagram and lamella thickness of SLCs and 2D crystals
can be tuned by the flexible alkyl tail and spacer length, due to their different
effects on enthalpy and entropy changes during SLC formation.
PMID- 28692100
TI - Observation of nanoimpact events of catalase on diamond ultramicroelectrodes by
direct electron transfer.
AB - We report electrochemical detection of single-catalase collisions at diamond
ultramicroelectrodes and show the operative mechanism involves direct enzyme
mediated charge transfer between electrode and solution. Hydrogen peroxide
increases the collision frequency, which fluorescence correlation spectroscopy
diffusion measurements suggest stems from an increase in the diffusion rate as
the underlying cause.
PMID- 28692101
TI - Molecular origin of urea driven hydrophobic polymer collapse and unfolding
depending on side chain chemistry.
AB - Osmolytes affect hydrophobic collapse and protein folding equilibria. The
underlying mechanisms are, however, not well understood. We report large-scale
conformational sampling of two hydrophobic polymers with secondary and tertiary
amide side chains using extensive molecular dynamics simulations. The calculated
free energy of unfolding increases with urea for the secondary amide, yet
decreases for the tertiary amide, in agreement with experiment. The underlying
mechanism is rooted in opposing entropic driving forces: while urea screens the
hydrophobic macromolecular interface and drives unfolding of the tertiary amide,
urea's concomitant loss in configurational entropy drives collapse of the
secondary amide. Only at sufficiently high urea concentrations bivalent urea
hydrogen bonding interactions with the secondary amide lead to further
stabilisation of its collapsed state. The observations provide a new angle on the
interplay between side chain chemistry, urea hydrogen bonding, and the role of
urea in attenuating or strengthening the hydrophobic effect.
PMID- 28692102
TI - Kinetic assembly of coordination networks.
AB - Kinetic assembly is an important method for obtaining desired materials in
chemical synthesis and materials science. We highlight the kinetic assembly of
porous coordination networks, which promote the production of interactive pore
sites. The interactive pore sites can activate or stabilize guest molecules. The
properties of interactive pores are typified by iodine chemisorption and small
sulfur encapsulation. Using interactive pores, we trapped small sulfur
allotropes, such as S2, cyclo-S3, bent-S3, and S6, demonstrating the importance
of interactive pore sites. Here, we address the important aspects of interactive
pore sites created by kinetic assembly of porous coordination networks.
PMID- 28692103
TI - Supercharging SpyCatcher toward an intrinsically disordered protein with stimuli
responsive chemical reactivity.
AB - We report a supercharged, intrinsically disordered protein, SpyCatcher(-),
possessing stimuli-responsive reactivity toward SpyTag with tunable yields
ranging from 4% to 98% depending on pH, temperature, ionic strength, etc. The CD
and NMR studies reveal that the reaction occurs through a folded intermediate
formed probably via a different mechanism from that of SpyCatcher.
PMID- 28692104
TI - C-ON bond homolysis of alkoxyamines: when too high polarity is detrimental.
AB - Throughout the last decade, the effect of electron withdrawing groups (EWGs) has
been known to play a role - minor or moderate depending on the nitroxyl fragment
R1R2NO - in the change in the homolysis rate constant (kd) for C-ON bond
homolysis in alkoxyamines (R1R2NOR). It has been shown that the effect of EWGs on
kd is described by a linear relationship with the electrical Hammett constant
sigmaI. Since then, linear multi-parameter relationships f(sigmaRS,nu,sigmaI)
have been developed to account for the effects involved in the changes in kd,
which are the stabilization of the released radical (sigmaRS) and the bulkiness
(nu) and polarity (sigmaI) of the alkyl fragment. Since a decade ago, new results
have been published highlighting the limits of such correlations. In this
article, previous multi-parameter linear relationships are amended using a
parabolic model, i.e. (sigmaI,nitroxide - sigmaI,alkyl)2, to describe the effect
of EWGs in the alkyl fragment on kd. In contrast to previous studies, these
improved linear multi-parameter relationships f(sigmaRS,nu,DeltasigmaI2) are able
to account for the presence of several EWGs on the alkyl fragment, R. An
unexpectedly strong solvent effect - a ca. 1500-fold increase in kd - from tert
butylbenzene to the water/methanol mixture is also observed for 3-((2,2,6,6
tetramethylpiperidin-1-yl)oxyl)pentane-2,4-dione 1b in comparison to a ca. 5-fold
increase in kd that is generally observed.
PMID- 28692105
TI - Prasugrel in critically ill patients.
AB - While prasugrel is indicated for the treatment of myocardial infarction, its
effects in the most severely affected patients requiring intensive care is
unknown, so that we measured the antiplatelet effects and sparse pharmacokinetics
of prasugrel in critically ill patients. Twenty-three patients admitted to
medical intensive care units, who were treated with 10 mg prasugrel once daily,
were included in this prospective trial. Critically ill patients responded poorly
to daily prasugrel treatment: adenosine diphosphate (ADP)-induced aggregation in
whole blood classified 65 % (95 % confidence intervals (CI) 43-84 %) of patients
as having high on treatment platelet reactivity, platelet function under high
shear rates even 74 % (95 %CI 52-90 %). There was only limited additional
inhibition provided 2 hours after the next dose of prasugrel. In contrast,
insufficient inhibition of the target was only seen in 26 % (95 %CI 10-48 %) of
patients as measured by the vasodilator-stimulated phosphoprotein phosphorylation
(VASP-P) assay. Low effective plasma levels of prasugrel active metabolite were
measured at trough [0.5 (quartiles 0.5-1.1) ng/ml at baseline], and 2 hours after
intake [5.7 (3.8-9.8) ng/ml], but showed coefficients of variation of ~70 %. In
sum, inhibition of platelet aggregation by prasugrel is not uniform but highly
variable in critically ill patients, similar to clopidogrel in a general
population. The pharmacokinetic measurements indicate that poor
absorption/metabolism of prasugrel may partly contribute while inflammation
induced heightened intrinsic platelet reactivity may also play a role.
PMID- 28692106
TI - Haemostasis biomarkers and risk of intracerebral haemorrhage in the REasons for
Geographic and Racial Differences in Stroke Study.
AB - Pathologic alterations in haemostasis cause bleeding disorders, but it is unknown
if variation within the normal range relates to intracerebral haemorrhage (ICH)
risk. It was our objective to assess the prospective associations of haemostasis
biomarkers with ICH risk. The REasons for Geographic and Racial Differences in
Stroke study (REGARDS) recruited 30,239 U. S. individuals aged >=45 years. ICH
was ascertained through biannual telephone contact and review of deaths followed
by medical record evaluation. Haemostasis biomarkers (factor VIII (FVIII), factor
IX (FIX), factor XI (FXI), fibrinogen, protein C, and D-dimer) were measured in a
case cohort study consisting of ICH and a 1,104 person cohort random sample. The
hazard ratio (HR) and 95 % confidence interval (CI) by biomarker were estimated
using Cox models and adjusted for ICH risk factors. Individuals with a prior
history of stroke, ICH or on warfarin were excluded. Over a median 5.8 years 66
ICH occurred. Fibrinogen, FVIII, FXI, and protein C were not associated with ICH
risk in any analysis. Lower FIX increased risk of ICH with the bottom versus the
top tertile of FIX associated with an HR of 5.68 (95 % CI 2.30, 14.05). D-dimer
demonstrated a non-linear relationship with a potential threshold effect with
increased risk only in the top 5th percentile (HR 3.22; 95 % CI 1.01, 10.31; pnon
linear = 0.04).In conclusion, low FIX levels within the normal range were
associated with increased ICH risk. These data suggest non-pathologic alterations
in haemostasis impact intracranial bleeding risk.
PMID- 28692107
TI - Whole blood ristocetin-activated platelet impedance aggregometry (Multiplate) for
the rapid detection of Von Willebrand disease.
AB - Von Willebrand disease (VWD) is the most common bleeding disorder, but no bedside
tests specific for Von Willebrand factor are available. The objective of this
study was to evaluate the diagnostic accuracy of whole blood ristocetin-induced
platelet aggregometry (WB-RIPA) in VWD. WB-RIPA was performed in VWD patients
(n=100) and healthy controls (n=17) using the Multiplate(r) platelet impedance
aggregometry platform. The diagnostic properties of the test were described as
sensitivity/specificity, positive and negative predictive value, and ROC area
under the curve (AUC). Patients with VWD had impaired platelet aggregation by WB
RIPA. At a cut-off of 98 U, the test sensitivity and specificity of WB-RIPA for
VWD was 0.95 and 0.53. A cut-off of 60 U provided a specificity of 1.00 with
reduced sensitivity of 0.76. All patients with type 3 VWD and >90 % of patients
with type 2 VWD were accurately distinguished from the controls. Incorrect
classifications were attributable to patients with type 1 VWD, showing partly
overlapping WB-RIPA results with healthy controls. Remarkably, these patients had
lower bleeding scores and higher VWF activity than other type 1 VWD patients.
Overall, WB-RIPA discriminated VWD patients from healthy controls accurately with
a ROC AUC of 0.94. These results show that WB-RIPA is a promising diagnostic test
for VWD, especially when timely results are required. Depending on the chosen
test threshold, WB-RIPA could be clinically used as a rule out test, or to
suggest patients in whom further testing for VWD is warranted.
PMID- 28692109
TI - Acute transmural myocardial infarction by coronary embolism in a patient with
JAK2 V617F-positive essential thrombocythemia.
PMID- 28692108
TI - Safety and efficacy of a glycoPEGylated rFVIII (turoctocog alpha pegol, N8-GP) in
paediatric patients with severe haemophilia A.
AB - Turoctocog alfa pegol (N8-GP, Novo Nordisk, Bagsvaerd, Denmark), an extended half
life glycoPEGylated recombinant factor VIII (rFVIII), is being developed for
prophylaxis and treatment of bleeds in haemophilia A patients. pathfinderTM5 is a
multinational, open-label, single-arm trial to assess safety, efficacy and
pharmacokinetics of N8-GP in paediatric (<12 years), previously treated patients.
Boys with severe haemophilia A (<1 % FVIII), no history of inhibitors and
previously treated with FVIII products (>50 exposure days [ED] for patients aged
0-5 years [younger cohort]; >150 ED for patients aged 6-11 years [older cohort])
were included. For prophylaxis, N8-GP was dosed at 50-75 IU/kg twice weekly;
bleeds were treated with 20-75 IU/kg. Half-life was estimated for the patients'
previous FVIII product and for N8-GP. Sixty-eight patients received N8-GP; none
developed inhibitors and no other concerns were identified. Median annualised
bleeding rate was 1.95 (1.94 and 1.97 in the younger and older cohorts,
respectively). Twenty-nine patients (42.6 %; 15 younger and 14 older children,
respectively) did not report any bleeding while on N8-GP prophylaxis; 39 patients
(57.4 %; 19 younger and 20 older children, respectively) reported 70 bleeds (all
mild/moderate). N8-GP treatment was successful for 78.6 % of bleeds in all
patients, 80.0 % in younger and 77.5 % in older patients. Most bleeds (80.0 %)
were treated with <=2 injections. Half-life ratio between N8-GP and the patients'
previous FVIII product was 1.85. N8-GP was well tolerated and provided effective
prophylaxis and treatment of bleeds in paediatric patients with severe
haemophilia A.
PMID- 28692110
TI - Plasma carboxypeptidase U (CPU, CPB2, TAFIa) generation during in vitro clot
lysis and its interplay between coagulation and fibrinolysis.
AB - Carboxypeptidase U (CPU, CPB2, TAFIa) is a basic carboxypeptidase that is able to
attenuate fibrinolysis. The inactive precursor procarboxypeptidase U is converted
to its active form by thrombin, the thrombin-thrombomodulin complex or plasmin.
The aim of this study was to investigate and characterise the time course of CPU
generation in healthy individuals. In plasma of 29 healthy volunteers, CPU
generation was monitored during in vitro clot lysis. CPU activity was measured by
means of an enzymatic assay that uses the specific substrate Bz-o-cyano-Phe-Arg.
An algorithm was written to plot the CPU generation curve and calculate the
parameters that define it. In all individuals, CPU generation was biphasic.
Marked inter-individual differences were present and a reference range was
determined. The endogenous CPU generation potential is the composite effect of
multiple factors. With respect to the first CPU activity peak characteristics, we
found correlations with baseline proCPU concentration, proCPU Thr325Ile
polymorphism, time to clot initiation and the clot lysis time. The second CPU
peak related with baseline proCPU levels and with the maximum turbidity of the
clot lysis profile. In conclusion, our method offers a technique to determine the
endogenous CPU generation potential of an individual. The parameters obtained by
the method quantitatively describe the different mechanisms that influence CPU
generation during the complex interplay between coagulation and fibrinolysis,
which are in line with the threshold hypothesis.
PMID- 28692111
TI - A randomised trial on the effect of anti-platelet therapy on the systemic
inflammatory response in human endotoxaemia.
AB - The use of acetylsalicylic acid (ASA) is associated with improved outcome in
patients with sepsis, and P2Y12 inhibitors have been suggested to also have
immunomodulatory effects. Therefore, we evaluated the effects of clinically
relevant combinations of antiplatelet therapy on the immune response in
experimental endotoxaemia in humans in vivo. Forty healthy subjects were
randomised to seven days of placebo, placebo with ASA, ticagrelor and ASA, or
clopidogrel and ASA treatment. Systemic inflammation was elicited at day seven by
intravenous administration of Escherichia coli endotoxin. ASA treatment
profoundly augmented the plasma concentration of pro-inflammatory cytokines, but
did not affect anti-inflammatory cytokines. Addition of either P2Y12 antagonist
to ASA did not affect any of the circulating cytokines, except for an attenuation
of the ASA-induced increase in TNFalpha by ticagrelor. Systemic inflammation
increased plasma adenosine, without differences between groups, and although
P2Y12 inhibition impaired platelet reactivity, there was no correlation with
cytokine responses.
PMID- 28692112
TI - The impact of bleeding disorders on the socioeconomic status of adult patients.
Results of a comparative single centre cohort study.
AB - The impact of inherited bleeding disorders on the socioeconomic status (SES) of
affected individuals is not clear. The SES of adult patients with congenital
bleeding disorders (PWBD) from a centre in Germany (age 42.3 +/- 15.0 years) was
compared to that of a gender- and age-matched control group of patients with
thrombophilia or a thrombotic event (PWT). Patients completed a questionnaire
including aspects of SES, impact of the disease on their lives, and health
related quality of life (HRQoL). Forty-five patients were enrolled in each group;
71 % of PBWD had a severe form of the bleeding disorder (FVIII/IX activity < 1 %
or VWD type 3), and 60 % of all PWBD were treated on-demand. PWBD had a lower
monthly income (p = 0.029) and a worse occupational status (p = 0.047) than PWT,
but there was no difference regarding the project-specific SES index. PWBD also
reported a worse HRQoL in the physical summary component score of the SF-36 (p <
0.001). More PWBD (69.8 %) reported a high impact of the disease on their lives
than PWT (33.3 %, p < 0.001). In summary, PWBD had a worse occupational status,
monthly income, health behaviour, HRQoL, and impact of the disease on their lives
compared to PWT, but not a significantly different SES in general.
PMID- 28692113
TI - Analysing the bioactive makeup of demineralised dentine matrix on bone marrow
mesenchymal stem cells for enhanced bone repair.
AB - Dentine matrix has proposed roles for directing mineralised tissue repair in
dentine and bone; however, the range of bioactive components in dentine and
specific biological effects on bone-derived mesenchymal stem cells (MSCs) in
humans are less well understood. The aims of this study were to further elucidate
the biological response of MSCs to demineralised dentine matrix (DDM) in
enhancing wound repair responses and ascertain key contributing components.
Dentine was obtained from human teeth and DDM proteins solubilised with
ethylenediaminetetraacetic acid (EDTA). Bone marrow derived MSCs were
commercially obtained. Cells with a more immature phenotype were then selected by
preferential fibronectin adhesion (FN-BMMSCs) for use in subsequent in vitro
assays. DDM at 10 ug/mL reduced cell expansion, attenuated apoptosis and was the
minimal concentration capable of inducing osteoblastic differentiation. Enzyme
linked immunosorbent assay (ELISA) quantification of growth factors indicated
physiological levels produced the above responses; transforming growth factor
beta (TGF-beta1) was predominant (15.6 ng/mg DDM), with relatively lower
concentrations of BMP-2, FGF, VEGF and PDGF (6.2-4.7 ng/mg DDM). Fractionation of
growth factors from other DDM components by heparin affinity chromatography
diminished osteogenic responses. Depletion of biglycan from DDM also attenuated
osteogenic potency, which was partially rescued by the isolated biglycan. Decorin
depletion from DDM had no influence on osteogenic potency. Collectively, these
results demonstrate the potential of DDM for the delivery of physiological levels
of growth factors for bone repair processes, and substantiate a role for biglycan
as an additional adjuvant for driving osteogenic pathways.
PMID- 28692114
TI - Association of endothelin-1 gene polymorphisms with essential hypertension in a
Chinese population.
AB - Endothelin-1 (ET-1) is the most potent endogenous vasoconstrictor and is involved
in several vascular disorders such as hypertension. Its strong interaction with
other vasoactive hormone systems suggests that the ET-1 gene (EDN1) is a
potential candidate molecule that influences the risk of developing hypertension.
Recently, two single nucleotide polymorphisms in EDN1 have been reported to be
associated with hypertension: Lys198Asn and 3A/4A (-134delA) located in the 5'
untranslated region. To determine the association of these two polymorphisms with
hypertension, we genotyped patients and controls (N = 537) and compared the
allele and genotype frequencies between groups. There was no significant
difference in the genotype frequencies of these two polymorphisms between healthy
controls and hypertension patients. Although previous reports have revealed a
significant interaction between the END1 Lys198Asn (G/T) polymorphism and body
mass index in association with hypertension, no such relationship was observed in
the present study. Further, we compared blood pressure among hypertensive
subjects and observed that neither systolic nor diastolic blood pressure was
significantly associated with variations in the genotypes of the two single
nucleotide polymorphisms. In summary, these two END1 polymorphisms do not appear
to affect the development of hypertension in the Chinese population.
PMID- 28692115
TI - An optimized protocol for DNA extraction in plants with a high content of
secondary metabolites, based on leaves of Mimosa tenuiflora (Willd.) Poir.
(Leguminosae).
AB - Some species are characterized by a high content of tannins, alkaloids, and
phenols in their leaves. These secondary metabolites are released during DNA
extraction and might hinder molecular studies based on PCR (polymerase chain
reaction). To provide an efficient method to extract DNA, Mimosa tenuiflora, an
important leguminous plant from Brazilian semiarid region used in popular
medicine and as a source of fuelwood or forage, was used. Eight procedures
previously reported for plants were tested and adapted from leaf tissues of M.
tenuiflora stored at -20 degrees C. The optimized procedure in this study
encompassed the utilization of phenol during deproteinization, increased
concentrations of cetyltrimethylammonium bromide and sodium chloride, and a
shorter period and lower temperature of incubation concerning other methods. The
extracted DNA did not present degradation, and amplification via PCR was
successful using ISSR, trnL, ITS, and ETS primers. Besides M. tenuiflora, this
procedure was also tested and proved to be efficient in genetic studies of other
plant species.
PMID- 28692116
TI - Variability among Capsicum baccatum accessions from Goias, Brazil, assessed by
morphological traits and molecular markers.
AB - Capsicum peppers are native to the Americas, with Brazil being a significant
diversity center. Capsicum baccatum accessions at Instituto Federal (IF) Goiano
represent a portion of the species genetic resources from central Brazil. We
aimed to characterize a C. baccatum working collection comprising 27 accessions
and 3 commercial cultivars using morphological traits and molecular markers to
describe its genetic and morphological variability and verify the occurrence of
duplicates. This set included 1 C. baccatum var. praetermissum and 29 C. baccatum
var. pendulum with potential for use in breeding programs. Twenty-two
morphological descriptors, 57 inter-simple sequence repeat, and 34 random
amplified polymorphic DNA markers were used. Genetic distance was calculated
through the Jaccard similarity index and genetic variability through cluster
analysis using the unweighted pair group method with arithmetic mean, resulting
in dendrograms for both morphological analysis and molecular analysis. Genetic
variability was found among C. baccatum var. pendulum accessions, and the
distinction between the two C. baccatum varieties was evident in both the
morphological and molecular analyses. The 29 C. baccatum var. pendulum genotypes
clustered in four groups according to fruit type in the morphological analysis.
They formed seven groups in the molecular analysis, without a clear
correspondence with morphology. No duplicates were found. The results describe
the genetic and morphological variability, provide a detailed characterization of
genotypes, and discard the possibility of duplicates within the IF Goiano C.
baccatum L. collection. This study will foment the use of this germplasm
collection in C. baccatum breeding programs.
PMID- 28692117
TI - Clinical significance and expression of PUMA, MCL-1, and p53 in human renal cell
carcinoma and para-carcinoma tissues.
AB - We investigated the expression level of p53 upregulated modulator of apoptosis
(PUMA), myeloid cell leukemia-I (MCL-1), and p53 in renal cell carcinoma (RCC)
and para-carcinoma tissues, as well as their clinical significance. The
expression levels of PUMA, MCL-1, and p53 in RCC and para-carcinoma tissues were
measured using immunohistochemical and quantitative real-time PCR methods.
Correlations between protein expression and pathological characteristics were
analyzed. Renal clear cell carcinoma showed elevated MCL-1 and p53 protein
expression (P > 0.05) and reduced PUMA expression as compared to that in para
carcinoma tissues. Spearman ranking correlation analysis showed that expression
of PUMA, MCL-1, and p53 in was negatively correlated with RCC (r = -0.504, P =
0.001; r = -0.413, P = 0.008). We also observed significant correlation between
MCL-1 expression and tumor differentiation (P < 0.05), where MCL-1 expression was
significantly higher in well-differentiated adenocarcinoma as compared to that in
medium or lowly differentiated adenocarcinoma. In addition, p53 expression was
highly correlated with TNM staging (P < 0.05). Single factor analysis on COX's
proportional hazard model indicated that postoperative survival rate and
prognosis of renal clear cell carcinoma was highly correlated with TNM staging (P
< 0.05). Quantitative real-time PCR analysis indicated higher expression of PUMA,
MCL-1, and p53 in cancer tissues as compared to that in para-carcinoma tissues (P
< 0.05).The expression of PUMA, MCL-1, and p53 can reflect the biological
behavior of renal cell carcinoma, and can be used to indicate tumor invasion,
progression, and prognosis.
PMID- 28692118
TI - Selection of maize inbred lines and gene expression for resistance to ear rot.
AB - In recent years, there has been a large incidence of fungi causing "ear rot" in
maize in Brazil, the main fungus being Fusarium verticillioides. The most
efficient and competitive alternative for control of this disease consists of
using maize hybrids resistant to this pathogen. Thus, the aims of this study were
to analyze the genetic variability of maize inbred lines in regard to resistance
to ear rot to observe if there is a maternal effect to resistance to ear rot, to
study genetic control of the traits evaluated in hybrids originating from inbred
lines of the maize breeding program at the Agriculture Department of Universidade
Federal de Lavras (Lavras, MG, Brazil), and characterize the gene expression
pattern related to the plant defense mechanism against F. verticillioides. High
genetic availability was observed for resistance to this disease among the inbred
lines evaluated. Considering combined diallel analysis, it was observed that the
mean square of general combining ability (GCA) was not significant for the
characteristic under study. However, specific combining ability (SCA) was
significant, which indicates the predominance of non-additive effects involved in
control of the characteristic for the population evaluated. A maternal effect was
not observed for the characteristic of ear rot resistance in this study. Inbred
lines 22, 58, and 91 showed potential for use in breeding programs aiming at
resistance to F. verticillioides. Only two genes, LOX8 and Hsp82, had a
satisfactory result that was able to be related to a plant defense mechanism when
there is ear rot infection, though expression of these genes was observed in only
one susceptible genotype. Thus, the genes LOX8 and Hsp82 are potential molecular
markers for selection of maize inbred lines resistant to F. verticillioides.
PMID- 28692119
TI - Improvement in orthopedic outcome score and reduction in IL-1beta, CXCL13, and
TNF-alpha in synovial fluid of osteoarthritis patients following arthroscopic
knee surgery.
AB - Knee osteoarthritis (KOA) is a common degenerative joint disease and immune
system dysregulation has been implicated in its pathogenesis. The effect of
arthroscopic knee surgery, an important method for KOA diagnosis and treatment,
on the expression of immune regulators remains poorly understood. We aimed to
investigate the clinical efficacy of such surgery and its impact on IL-1beta,
CXCL13, and TNF-alpha expression in the knee joint synovial fluid of
osteoarthritis patients. Fifty-seven patients having undergone arthroscopic knee
surgery in our hospital were included. Visual analog scale (VAS) and Lysholm
scores were recorded before surgery, and knee joint synovial fluid was collected
during the procedure. According to Outerbridge cartilage damage score (grade 0,
1, 2, 3, or 4), patients were divided into five groups. In addition, VAS and
Lysholm scores were recorded and knee joint synovial fluid was collected after a
six-month follow-up period. Expression of IL-1beta, CXCL13, and TNF-alpha in
synovial fluid samples was then measured. In each group, levels of these
molecules and VAS and Lysholm scores were significantly lower after surgery (P <
0.05). IL-1beta, CXCL13, and TNF-alpha levels were significantly elevated in
patients with higher cartilage damage scores compared to those with lower scores.
Arthroscopic knee surgery can reduce IL-1beta, CXCL13, and TNF-alpha levels in
the knee joint synovial fluid of osteoarthritis patients. Moreover, reduced
presence of these molecules correlates with clinical improvement of this
condition. Therefore, reduction in IL-1beta, CXCL13, and TNF-alpha expression
might be used as a factor for long-term osteoarthritis prognosis.
PMID- 28692120
TI - Bayesian analyses of genetic parameters for growth traits in Nellore cattle
raised on pasture.
AB - This study was carried out to investigate (co)variance components and genetic
parameters for growth traits in beef cattle using a multi-trait model by Bayesian
methods. Genetic and residual (co)variances and parameters were estimated for
weights at standard ages of 120 (W120), 210 (W210), 365 (W365), and 450 days
(W450), and for pre- and post-weaning daily weight gain (preWWG and postWWG) in
Nellore cattle. Data were collected over 16 years (1993-2009), and all animals
were raised on pasture in eight farms in the North of Brazil that participate in
the National Association of Breeders and Researchers. Analyses were run by the
Bayesian approach using Gibbs sampler. Additive direct heritabilities for W120,
W210, W365, and W450 and for preWWG and postWWG were 0.28 +/- 0.013, 0.32 +/-
0.002, 0.31 +/- 0.002, 0.50 +/- 0.026, 0.61 +/- 0.047, and 0.79 +/- 0.055,
respectively. The estimates of maternal heritability were 0.32 +/- 0.012, 0.29 +/
0.004, 0.30 +/- 0.005, 0.25 +/- 0.015, 0.23 +/- 0.017, and 0.22 +/- 0.016,
respectively, for W120, W210, W365, and W450 and for preWWG and postWWG. The
estimates of genetic direct additive correlation among all traits were positive
and ranged from 0.25 +/- 0.03 (preWWG and postWWG) to 0.99 +/- 0.00 (W210 and
preWWG). The moderate to high estimates of heritability and genetic correlation
for weights and daily weight gains at different ages is suggestive of genetic
improvement in these traits by selection at an appropriate age. Maternal genetic
effects seemed to be significant across the traits. When the focus is on direct
and maternal effects, W210 seems to be a good criterium for the selection of
Nellore cattle considering the importance of this breed as a major breed of beef
cattle not only in Northern Brazil but all regions covered by tropical pastures.
As in this study the genetic correlations among all traits were high, the
selection based on weaning weight might be a good choice because at this age
there are two important effects (maternal and direct genetic effects). In
contrast, W120 should be preferred when the objective is improving the maternal
ability of the dams. Furthermore, selection for postWWG can be used if the
animals show both heavier weaning weights and high growth rate after weaning
because it is possible to shorten the time between weaning and slaughter based on
weaning weight, postWWG, and desired weight at the time of slaughter.
PMID- 28692121
TI - Molecular analysis of the GSTT1 gene polymorphism in patients with clinical
manifestation of atherosclerosis.
AB - Atherosclerosis is a chronic inflammatory disease formed by the accumulation of
lipids in the innermost layer and large-caliber artery (tunica intima). This
accumulation, along with platelet factors, stimulates the proliferation of muscle
cells in this region. Over than 400 genes may be related to the pathology since
they regulate endothelial function, coagulation, inflammation, metabolism of
amino acids, lipids, and carbohydrates. Glutathione S-transferases (GST) are
enzymes that catalyze the polymorphic detoxification of metabolites produced by
oxidative stress within the cells, which is induced by reactive oxygen species.
GSTs are one of the defense mechanisms against oxidative stress damage. Due to
genetic, cultural, and environmental factors, the rate of atherosclerosis is
higher; however, an early diagnosis is crucial for the prevention and treatment
of several complications related to the disease. The present study aimed to
analyze the frequency of GSTT1 genotypes regarding the presence or absence of the
polymorphism in patients with clinical manifestation of atherosclerosis. We
collected 200 samples of peripheral blood of patients with the previous diagnosis
of atherosclerosis based on clinical examination and imaging, and 100 samples of
peripheral blood to compose the control group of patients without clinical
manifestation of atherosclerosis. The polymorphism was assessed by PCR and
analyzed on the agarose gel stained with 2.0% ethidium bromide. The frequency of
the GSTT1 gene polymorphism was compared using the chi-square test (P < 0.05) and
the G-test. In the case group, we detected 85.5% of patients with the GSTT1
genotype present and 14.5% of patients with the null genotype. A significant
difference was observed between groups (case vs control) for the presence of the
GSTT1 polymorphism. According to the analysis of the variable alcohol
consumption, we found that in the case group the presence of the GSTT1 gene was
higher in individuals who reported not drinking alcohol. In this study, the
presence of the GSTT1 gene polymorphism in male patients with atherosclerosis was
1.5 times higher when compared to female patients. Regarding the variable time of
smoking, we found that this genotype was more frequent in smokers for both case
and control groups.
PMID- 28692122
TI - Alteration of -656(G/T) and -607(C/A) polymorphisms in interleukin-18 (IL-18)
gene in house dust mite-sensitive allergic rhinitis patients in Thailand.
AB - Allergic rhinitis (AR) is an IgE-mediated inflammation of the nasal membranes,
which is naturally triggered by aeroallergens. House dust mites (HDM) are the
most common inhalant allergens. Interleukin-18 (IL-18) has been established as an
essential cytokine that can activate the generation of IgE. This randomized
controlled study aimed to identify the possible relationship of the genetic
variations in the IL-18 gene with AR in mite-sensitive Thai patients. Study
subjects consisted of 150 AR patients and 50 normal participants. Genomic DNA of
30 randomized AR patients and 30 randomized controls were screened by sequencing
for the selection of candidate single nucleotide polymorphisms (SNPs), and
further analyzed by polymerase chain reaction-restriction fragment length
polymorphism (PCR-RFLP) assay for all subjects. The following five SNPs were
detected in the IL-18 gene: -656 G/T, -607 C/A, and -137 G/C in promoter 1 and
920 C/T and -373 C/G in promoter 2. The results showed that -656 G/T and -607 C/A
SNPs were significantly correlated with IgE levels specific to Dermatophagoides
pteronyssinus (Der p) allergen (P = 0.045 and P = 0.045, respectively), and
significant differences were observed in the genotype distribution of AR patients
when compared with controls [P = 0.044 and P = 0.044, respectively; odds ratios
(ORs): 1.941 (95%CI, 1.014-3.715) and 1.941 (95%CI, 1.014-3.715), respectively].
Our findings indicate that the IL-18 alleles, -656T (rs1946519) and -607A
(rs1946518), might be associated with the higher production of Der p allergen
specific IgE in mite-sensitive AR patients.
PMID- 28692123
TI - Mitochondrial DNA control region analysis of three ethnic populations in lower
Northern part of Thailand.
AB - The lower northern part of Thailand contains various genetically diverse ethnic
populations. The sequences of the mitochondrial DNA hypervariable region were
studied in three ethnic populations inhabiting Phitsanulok Province. One hundred
and nine nucleotide sequences - 53, 29, and 27 from Hmongs (Hill tribe), Lao
Songs, and Thai-Siams, respectively - were collected. The haplotypes were
generated from 1130 nucleotides of the entire control region. Eighty-six
haplotypes were found in the three ethnic populations, and no shared haplotypes
were found between populations. Point heteroplasmy was noted at position 311 (C
>Y). Haplotypes with ACAC-insertion at position 512 were observed in immigrant
individuals from the Lao Song population. The Thai-Siam population showed higher
genetic diversity than the other populations. The Hmong and Lao Song populations
showed less genetic diversity than those living in their original area. The
neutrality testing suggested that the result might be influenced by genetic
drift.
PMID- 28692124
TI - Genetic variability of a Brazilian Capsicum frutescens germplasm collection using
morphological characteristics and SSR markers.
AB - Characterization studies provide essential information for the conservation and
use of germplasm in plant breeding programs. In this study, 103 Capsicum
frutescens L. accessions from the Active Germplasm Bank of Embrapa Hortalicas,
representative of all five Brazilian geographic regions, were characterized based
on morphological characteristics and microsatellite (or simple sequence repeat -
SSR) molecular markers. Morphological characterization was carried out using 57
descriptors, and molecular characterization was based on 239 alleles from 24
microsatellite loci. From the estimates of genetic distances among accessions,
based on molecular characterization, a cluster analysis was carried out, and a
dendrogram was established. Correlations between morphological and molecular
variables were also estimated. Twelve morphological descriptors were monomorphic
for the set of C. frutescens accessions, and those with the highest degree of
polymorphism were stem length (14.0 to 62.0 cm), stem diameter (1.0 to 4.2 cm),
days to flowering (90 to 129), days to fruiting (100 to 140), fruit weight (0.1
to 1.4 g), fruit length (0.6 to 4.6 cm), and fruit wall thickness (0.25 to 1.5
mm). The polymorphism information content for the SSR loci varied from 0.36 (EPMS
417) to 0.75 (CA49), with an overall mean of 0.57. The correlation value between
morphological and molecular characterization data was 0.6604, which was
statistically significant. Fourteen accessions were described as belonging to the
morphological type tabasco, 85 were described as malagueta, and four were
malaguetinha, a morphological type confirmed in this study. The typical
morphological pattern of malagueta was described. Six similarity groups were
established for C. frutescens based on the dendrogram and are discussed
individually. The genetic variability analyzed in the study highlights the
importance of characterizing genetic resources available for the development of
new C. frutescens cultivars with the potential for various niche markets.
PMID- 28692125
TI - Steroid metabolism gene polymorphisms and their implications on breast and
ovarian cancer prognosis.
AB - A role for estrogen in the etiology of breast and ovarian cancers has been
suggested; therefore, genetic polymorphisms in steroid metabolism genes could be
involved in the carcinogenesis of these tumors. We have aimed to investigate the
role of GSTP1 and CYP17 polymorphisms and their correlation with MSI
(microsatellite instability) and LOH (loss of heterozygosity) in AR, ERbeta and
CYP19 genes in women from Espirito Santo State, Brazil. The study population
consisted of 107 female breast and 24 ovarian tumors. GSTP1 and CYP17
polymorphisms were detected by polymerase chain reaction (PCR) amplification
followed by restriction fragment length polymorphism (RFLP) analysis while MSI
and LOH were analyzed by PCR. GSTP1 and CYP17 polymorphisms alone were not
associated with an increased risk for breast or ovarian tumors. However, when
combined with MSI/LOH in AR, ERbeta and CYP19 genes, we were able to detect
significant associations with the GSTP1 wild-type genotype in PR (progesterone
receptor) negative breast cancers or the CYP17 wild-type genotype in ER (estrogen
receptor) and PR-negative breast tumors. No associations with ovarian tumors were
detected. Our results suggest that wild-type GSTP1 or CYP17 genes when combined
with LOH/MSI in steroid metabolism genes may play a role in ER and/or PR negative
breast cancers. These data support the hypothesis that genes related to steroid
metabolism are important in the characterization of breast cancer and that the
analysis of single polymorphisms may not be sufficient.
PMID- 28692126
TI - Environmental stratifications for soybean cultivar recommendation and its
consistency over time.
AB - Stratification of environments is a strategy to capitalize genotype x environment
(GxE) interaction, which can optimize the process of assessment and cultivar
recommendation, increasing productivity in a target environmental population. The
objective of this study was to assess environmental stratification methods based
on the analysis of GxE interaction, to identify consistent agronomic zones across
time for soybean. Grain yield data of inbred lines from three maturity groups
(early, medium, and late) were used. Lines and cultivars were tested in regional
variety trials during three growing seasons at eighteen locations in the tropics
of Central Brazil. Three methods were applied to stratify the environments. The
first was based on joint analyses of variance for all the pairs of locations
within each growing year. The second was based on a distance measure between each
pair of locations, which was related to the GxE interaction estimated via
additive main effects and multiplicative interaction analysis. The third was
based on the approach of winning genotypes. The stratification results from the
first two methods were not consistent across the growing seasons. However, the
winning genotype approach provided consistent environmental stratification across
years. From locations used in the genotypic assessment, three environmental
clusters were identified for the early and medium maturity groups of soybean, and
four clusters for the late maturity group. The use of different genotypic sets
across years reinforces the predictive value of the environmental stratification
established.
PMID- 28692127
TI - Diversity and genetic structure of the native Brazil nut tree (Bertholletia
excelsa Bonpl.) population.
AB - The present study was carried out in a native Brazil nut tree population
(Bertholletia excelsa Bonpl., Lecythidaceae) to assess its genetic diversity and
structure. Ten microsatellite markers were used to genotype 198 adult trees (B.
excelsa). The population presented high genetic diversity and inbreeding absence
rates. The empirical Bayesian method showed three distinct groups in the
structure of this population. Molecular analysis of variance showed 98%
variability within groups, and 2% between groups. The genetic divergence (FST)
indicated little difference between groups; thus, suggesting efficient gene flow
between the analyzed B. excelsa adult trees.
PMID- 28692128
TI - Carpal tunnel syndrome in inherited neuropathies: A retrospective survey.
AB - INTRODUCTION: This study evaluates carpal tunnel syndrome (CTS) symptom severity,
functional status, and outcome of CTS therapies in patients with inherited
neuropathies. METHODS: Validated questionnaires were used to compare symptom
severity and functional status in patients with and without a diagnosis of CTS
and a diagnosis of an inherited neuropathy. RESULTS: 309 patients with inherited
neuropathies participated in this study. The CTS symptom severity score (SSS) was
found to be the most useful tool in assessing CTS severity in patients with
inherited neuropathy. Splint therapy and surgery were associated with significant
improvement in carpal tunnel symptoms as measured through the SSS. DISCUSSION:
This study provides insight into the assessment of CTS symptom severity and
patient-reported outcomes to CTS therapy in individuals with inherited
neuropathies. The SSS appears useful for evaluation of CTS symptoms and patient
reported outcomes following CTS interventions in individuals with inherited
neuropathies. Muscle Nerve 57: 388-394, 2018.
PMID- 28692129
TI - Distortion-free diffusion MRI using an MRI-guided Tri-Cobalt 60 radiotherapy
system: Sequence verification and preliminary clinical experience.
AB - PURPOSE: Monitoring tumor response during the course of treatment and adaptively
modifying treatment plan based on tumor biological feedback may represent a new
paradigm for radiotherapy. Diffusion MRI has shown great promises in assessing
and predicting tumor response to radiotherapy. However, the conventional
diffusion-weighted single-shot echo-planar-imaging (DW-ssEPI) technique suffers
from limited resolution, severe distortion, and possibly inaccurate ADC at low
field strength. The purpose of this work was to develop a reliable, accurate and
distortion-free diffusion MRI technique that is practicable for longitudinal
tumor response evaluation and adaptive radiotherapy on a 0.35 T MRI-guided
radiotherapy system. METHODS: A diffusion-prepared turbo spin echo readout (DP
TSE) sequence was developed and compared with the conventional diffusion-weighted
single-shot echo-planar-imaging sequence on a 0.35 T MRI-guided radiotherapy
system (ViewRay). A spatial integrity phantom was used to quantitate and compare
the geometric accuracy of the two diffusion sequences for three orthogonal
orientations. The apparent diffusion coefficient (ADC) accuracy was evaluated on
a diffusion phantom under both 0 degrees C and room temperature to cover a
diffusivity range between 0.40 * 10-3 and 2.10 * 10-3 mm2 /s. Ten room
temperature measurements repeated on five different days were conducted to assess
the ADC reproducibility of DP-TSE. Two glioblastoma (GBM) and six sarcoma
patients were included to examine the in vivo feasibility. The target
registration error (TRE) was calculated to quantitate the geometric accuracy
where structural CT or MR images were co-registered to the diffusion images as
references. ADC maps from DP-TSE and DW-ssEPI were calculated and compared. A
tube phantom was placed next to patients not treated on ViewRay, and ADCs of this
reference tube were also compared. RESULTS: The proposed DP-TSE passed the
spatial integrity test (< 1 mm within 100 mm radius and < 2 mm within 175 mm
radius) under the three orthogonal orientations. The detected errors were 0.474
+/- 0.355 mm, 0.475 +/- 0.287 mm, and 0.546 +/- 0.336 mm in the axial, coronal,
and sagittal plane. DW-ssEPI, however, failed the tests due to severe distortion
and low signal intensity. Noise correction must be performed for the DW-ssEPI to
avoid ADC quantitation errors, whereas it is optional for DP-TSE. At 0 degrees
C, the two sequences provided accurate quantitation with < 3% variation with the
reference. In the room temperature study, discrepancies between ADCs from DP-TSE
and the reference were within 4%, but could be as high as 8% for DW-ssEPI after
the noise correction. Excellent ADC reproducibility with a coefficient of
variation < 5% was observed among the 10 measurements of DP-TSE, indicating
desirable robustness for ADC-based tumor response assessment. In vivo TRE in DP
TSE was less than 1.6 mm overall, whereas it could be greater than 12 mm in DW
ssEPI. For GBM patients, the CSF and brain tissue ADCs from DP-TSE were within
the ranges found in literature. ADC differences between the two techniques were
within 8% among the six sarcoma patients. For the reference tube that had a
relatively low diffusivity, the two diffusion sequences provided matched
measurements. CONCLUSION: A diffusion technique with excellent geometric
fidelity, accurate, and reproducible ADC measurement was demonstrated for
longitudinal tumor response assessment using a low-field MRI-guided radiotherapy
system.
PMID- 28692130
TI - The primary case is not enough: Variation among individuals, groups and social
networks modify bacterial transmission dynamics.
AB - The traits of the primary case of an infectious disease outbreak, and the
circumstances for their aetiology, potentially influence the trajectory of
transmission dynamics. However, these dynamics likely also depend on the traits
of the individuals with whom the primary case interacts. We used the social
spider Stegodyphus dumicola to test how the traits of the primary case, group
phenotypic composition and group size interact to facilitate the transmission of
a GFP-labelled cuticular bacterium. We also compared bacterial transmission
across experimentally generated "daisy-chain" vs. "star" networks of social
interactions. Finally, we compared social network structure across groups of
different sizes. Groups of 10 spiders experienced more bacterial transmission
events compared to groups of 30 spiders, regardless of groups' behavioural
composition. Groups containing only one bold spider experienced the lowest levels
of bacterial transmission regardless of group size. We found no evidence for the
traits of the primary case influencing any transmission dynamics. In a second
experiment, bacteria were transmitted to more individuals in experimentally
induced star networks than in daisy-chains, on which transmission never exceeded
three steps. In both experimental network types, transmission success depended
jointly on the behavioural traits of the interacting individuals; however, the
behavioural traits of the primary case were only important for transmission on
star networks. Larger social groups exhibited lower interaction density (i.e. had
a low ratio of observed to possible connections) and were more modular, i.e. they
had more connections between nodes within a subgroup and fewer connections across
subgroups. Thus, larger groups may restrict transmission by forming fewer
interactions and by isolating subgroups that interacted with the primary case.
These findings suggest that accounting for the traits of single exposed hosts has
less power in predicting transmission dynamics compared to the larger scale
factors of the social groups in which they reside. Factors like group size and
phenotypic composition appear to alter social interaction patterns, which leads
to differential transmission of microbes.
PMID- 28692131
TI - Vitis vinifera root and leaf metabolic composition during fruit maturation:
implications of defoliation.
AB - Grapevine (Vitis vinifera) roots and leaves represent major carbohydrate and
nitrogen (N) sources, either as recent assimilates, or mobilized from labile or
storage pools. This study examined the response of root and leaf primary
metabolism following defoliation treatments applied to fruiting vines during
ripening. The objective was to link alterations in root and leaf metabolism to
carbohydrate and N source functioning under conditions of increased fruit sink
demand. Potted grapevine leaf area was adjusted near the start of veraison to 25
primary leaves per vine compared to 100 leaves for the control. An additional
group of vines were completely defoliated. Fruit sugar and N content development
was assessed, and root and leaf starch and N concentrations determined. An
untargeted GC/MS approach was undertaken to evaluate root and leaf primary
metabolite concentrations. Partial and full defoliation increased root
carbohydrate source contribution towards berry sugar accumulation, evident
through starch remobilization. Furthermore, root myo-inositol metabolism played a
distinct role during carbohydrate remobilization. Full defoliation induced
shikimate pathway derived aromatic amino acid accumulation in roots, while
arginine accumulated after full and partial defoliation. Likewise, various leaf
amino acids accumulated after partial defoliation. These results suggest elevated
root and leaf amino N source activity when leaf N availability is restricted
during fruit ripening. Overall, this study provides novel information regarding
the impact of leaf source restriction, on metabolic compositions of major
carbohydrate and N sources during berry maturation. These results enhance the
understanding of source organ carbon and N metabolism during fruit maturation.
PMID- 28692132
TI - Plasma protein electrophoresis as a prognostic indicator in Aspergillus species
infected Gentoo penguins (Pygoscelis papua papua).
AB - BACKGROUND: Avian aspergillosis presents a significant threat to captive penguin
populations. Currently, a lack of objective prognostic factors limits disease
staging, objective reassessment throughout treatment, comparative evaluation of
treatment regimes, and appropriate timing of euthanasia. OBJECTIVE: The study
objective was to investigate absolute and relative plasma protein fractions by
agarose gel electrophoresis (EPH) as predictors of survival in Gentoo penguins
(Pygoscelis papua papua) under treatment for aspergillosis. METHODS: One hundred
and eighty-three EPH profiles from individual clinical cases were examined
retrospectively. Animal survival to 90 days post sampling was established from
clinical records; birds either survived (n = 146) or died within 90 days (n =
37), and time to death was recorded. RESULTS: Fourteen variables showed
statistically significant differences (P < .05) between surviving and dying
birds. Receiver operating characteristic curve analysis identified total albumin
concentration (albumin + prealbumin) and albumin-to-globulin (A:G) ratio as
having strongest discriminatory values (95% CI) at 0.788 (0.710-0.866) and 0.784
(0.696-0.871), respectively. Albumin (concentration and percentage of total
protein) displayed moderate discriminatory value but additionally a weak positive
correlation with time to death (95% CI); r = .353 (0.033-0.608) and .424 (0.116
0.658), respectively. CONCLUSIONS: Optimized test cutoffs for total albumins,
albumin (concentration and percentage of total protein), and A:G ratio achieved
moderate sensitivity and specificity, strong negative predictive values, but weak
positive predictive values due to a low prevalence of death. Selection of
appropriate test cutoff values may provide valuable adjunctive prognostic tools
for clinical decision-making when the prognosis is difficult to assess
clinically.
PMID- 28692133
TI - New insights into enterocin CRL35: mechanism of action and immunity revealed by
heterologous expression in Escherichia coli.
AB - The role of the class IIa bacteriocin membrane receptor protein remains unclear,
and the following two different mechanisms have been proposed: the bacteriocin
could interact with the receptor changing it to an open conformation or the
receptor might act as an anchor allowing subsequent bacteriocin insertion and
membrane disruption. Bacteriocin-producing cells synthesize an immunity protein
that forms an inactive bacteriocin-receptor-immunity complex. To better
understand the molecular mechanism of enterocin CRL35, the peptide was expressed
as the suicidal probe EtpM-enterocin CRL35 in Escherichia coli, a naturally
insensitive microorganism since it does not express the receptor. When the
bacteriocin is anchored to the periplasmic face of the plasma membrane through
the bitopic membrane protein, EtpM, E. coli cells depolarize and die. Moreover,
co-expression of the immunity protein prevents the deleterious effect of EtpM
enterocin CRL35. The binding and anchoring of the bacteriocin to the membrane has
demonstrated to be a sufficient condition for its membrane insertion. The final
step of membrane disruption by EtpM-enterocin CRL35 is independent from the
receptor, which means that the mannose PTS might not be involved in the pore
structure. In addition, the immunity protein can protect even in the absence of
the receptor.
PMID- 28692134
TI - Dissociative Ionization and Thermal Decomposition of Cyclopentanone.
AB - Despite the growing use of renewable and sustainable biofuels in transportation,
their combustion chemistry is poorly understood, limiting our efforts to reduce
harmful emissions. Here we report on the (dissociative) ionization and the
thermal decomposition mechanism of cyclopentanone, studied using imaging
photoelectron photoion coincidence spectroscopy. The fragmentation of the ions is
dominated by loss of CO, C2 H4 , and C2 H5 , leading to daughter ions at m/z 56
and 55. Exploring the C5 H8 O.+ potential energy surface reveals hydrogen
tunneling to play an important role in low-energy decarbonylation and probably
also in the ethene-loss processes, yielding 1-butene and methylketene cations,
respectively. At higher energies, pathways without a reverse barrier open up to
oxopropenyl and cyclopropanone cations by ethyl-radical loss and a second ethene
loss channel, respectively. A statistical Rice-Ramsperger-Kassel-Marcus model is
employed to test the viability of this mechanism. The pyrolysis of cyclopentanone
is studied at temperatures ranging from about 800 to 1100 K. Closed-shell
pyrolysis products, namely 1,3-butadiene, ketene, propyne, allene, and ethene,
are identified based on their photoion mass-selected threshold photoelectron
spectrum. Furthermore, reactive radical species such as allyl, propargyl, and
methyl are found. A reaction mechanism is derived incorporating both stable and
reactive species, which were not predicted in prior computational studies.
PMID- 28692135
TI - Self-Templated Stepwise Synthesis of Monodispersed Nanoscale Metalated Covalent
Organic Polymers for In Vivo Bioimaging and Photothermal Therapy.
AB - Size- and shape-controlled growth of nanoscale microporous organic polymers
(MOPs) is a big challenge scientists are confronted with; meanwhile, rendering
these materials for in vivo biomedical applications is still scarce. In this
study, a monodispersed nanometalated covalent organic polymer (MCOP, M=Fe, Gd)
with sizes around 120 nm was prepared by a self-templated two-step solution-phase
synthesis method. The metal ions (Fe3+ , Gd3+ ) played important roles in
generating a small particle size and in the functionalization of the products
during the reaction with p-phenylenediamine (Pa). The resultant Fe-Pa complex was
used as a template for the subsequent formation of MCOP following the Schiff base
reaction with 1,3,5-triformylphloroglucinol (Tp). A high tumor suppression
efficiency for this Pa-based COP is reported for the first time. This study
demonstrates the potential use of MCOP as a photothermal agent for photothermal
therapy (PTT) and also provides an alternative route to fabricate nano-sized
MCOPs.
PMID- 28692136
TI - Measurement centration and zone diameter in anterior, posterior and total corneal
astigmatism in keratoconus.
AB - PURPOSE: To investigate the central and paracentral astigmatism and the
significance of centration and measurement zone diameter compared to a 3-mm pupil
centred measurement zone in keratoconus and in healthy eyes. METHODS: Twenty
eight right eyes from 28 KC patients with an inferotemporal cone were selected
according to specified criteria based on Oculus Pentacam HR(r) measurements and
were matched with healthy control eyes. The flat (K1) and steep (K2) keratometry
readings were registered from the 'Total Corneal Refractive Power' (TCRP) display
as well as the anterior and posterior corneal astigmatism displays (ACA and PCA,
respectively). Astigmatic power vectors KP0 and KP45 were calculated and analysed
for a 6-mm and two 3-mm zones centred on the corneal apex and the pupil, and for
8 paracentral 3-mm zones. RESULTS: The astigmatism was generally higher in KC.
Many astigmatic values in KC differed between the 3-mm pupil-centred and the 3-
and 6-mm apex-centred zones in KC. In the controls, no corresponding differences
between measurement zones were seen, apart from PCA, which differed. The
magnitude and direction of KP0 and KP45 varied greatly between the paracentral
measurements in KC. CONCLUSION: Centration and measurement zone diameter have
great impacts on the astigmatic values in KC. A small pupil-centred measurement
zone should be considered when evaluating the astigmatism in KC.
PMID- 28692137
TI - Portable perfusion phantom for quantitative DCE-MRI of the abdomen.
AB - PURPOSE: The aim of this study was to develop a portable perfusion phantom and
validate its utility in quantitative dynamic contrast-enhanced magnetic resonance
imaging of the abdomen. METHODS: A portable perfusion phantom yielding a
reproducible contrast enhancement curve (CEC) was developed. A phantom package
including perfusion and static phantoms were imaged simultaneously with each of
three healthy human volunteers in two different 3T MR scanners. Look-up tables
correlating reference (known) contrast concentrations with measured ones were
created using either the static or perfusion phantom. Contrast maps of image
slices showing four organs (liver, spleen, pancreas, and paravertebral muscle)
were generated before and after data correction using the look-up tables. The
contrast concentrations at 4.5 min after dosing in each of the four organs were
averaged for each volunteer. The mean contrast concentrations (4 organs * 3
volunteers = 12) were compared for the two scanners, and the intra-class
correlation coefficient (ICC) was calculated. Also, the ICC of the mean Ktrans
values between the two scanners was calculated before and after data correction.
RESULTS: The repeatability coefficient of CECs of perfusion phantom was higher
than 0.997 in all measurements. The ICC of the tissue contrast concentrations
between the two scanners was 0.693 before correction, but increased to 0.974
after correction using the look-up tables (LUTs) of perfusion phantom. However,
the ICC was not increased after correction using static phantom (ICC: 0.617).
Similarly, the ICC of the Ktrans values was 0.899 before correction, but
increased to 0.996 after correction using perfusion phantom LUTs. The ICC of the
Ktrans values, however, was not increased when static phantom LUTs were used
(ICC: 0.866). CONCLUSIONS: The perfusion phantom reduced variability in
quantitating contrast concentration and Ktrans values of human abdominal tissues
across different MR units, but static phantom did not. The perfusion phantom has
the potential to facilitate multi-institutional clinical trials employing
quantitative DCE-MRI to evaluate various abdominal malignancies.
PMID- 28692138
TI - The 2025 Big "G" Geriatrician: Defining Job Roles to Guide Fellowship Training.
AB - Changes in health care that are already in progress, including value- and
population-based care, use of new technologies for care, big data and machine
learning, and the patient as consumer and decision maker, will determine the job
description for geriatricians practicing in 2025. Informed by these future
certainties, 115 geriatrics educators attending the 2016 Donald W. Reynolds
Foundation Annual meeting identified five 2025 geriatrician job roles:
complexivist; consultant; health system leader and innovator; functional
preventionist; and educator for big "G" and little "g" providers. By identifying
these job roles, geriatrics fellowship training can be preemptively redesigned.
PMID- 28692139
TI - The health threats to people with asthma through asthma-associated infectious
disease comorbidities are largely under-recognized.
PMID- 28692140
TI - Network-based Approaches in Pharmacology.
AB - In drug discovery, network-based approaches are expected to spotlight our
understanding of drug action across multiple layers of information. On one hand,
network pharmacology considers the drug response in the context of a cellular or
phenotypic network. On the other hand, a chemical-based network is a promising
alternative for characterizing the chemical space. Both can provide complementary
support for the development of rational drug design and better knowledge of the
mechanisms underlying the multiple actions of drugs. Recent progress in both
concepts is discussed here. In addition, a network-based approach using drug
target-therapy data is introduced as an example.
PMID- 28692142
TI - Big 'G' and Little 'g' Geriatrics Education for Physicians.
AB - In the July 2016 issue of this journal, Dr. Mary Tinetti proposed that geriatric
medicine abandon attempts to increase the numbers of board-certified
geriatricians and change focus to the development of a "small elite workforce."
What would be gained and what sacrificed by accepting this challenge? We agree
that the best clinical use of a scarce resource, specialty trained geriatricians,
is to care for frail, complex, severely ill elderly adults and to help design and
study novel interventions in research, education, and care models to improve the
care of all older adults, but for this to happen, all other providers must attain
specific competency in the care of older adults. This article responds and
discusses alternative pathways for teaching geriatrics care, training
specialists, and geriatrics fellows.
PMID- 28692141
TI - A discontinuous autoinhibitory module masks the A1 domain of von Willebrand
factor.
AB - Essentials The mechanism for the auto-inhibition of von Willebrand factor (VWF)
remains unclear. Hydrogen exchange of two VWF A1 fragments with disparate
activities was measured and compared. Discontinuous residues flanking A1 form a
structural module that blocks A1 binding to the platelet. Our results suggest a
potentially unified model of VWF activation. Click to hear an ISTH Academy
presentation on the domain architecture of VWF and activation by elongational
flow by Dr Springer SUMMARY: Background How von Willebrand factor (VWF) senses
and responds to shear flow remains unclear. In the absence of shear flow, VWF or
its fragments can be induced to bind spontaneously to platelet GPIbalpha.
Objectives To elucidate the auto-inhibition mechanism of VWF. Methods Hydrogen
deuterium exchange (HDX) of two recombinant VWF fragments expressed from baby
hamster kidney cells were measured and compared. Results The shortA1 protein
contains VWF residues 1261-1472 and binds GPIbalpha with a significantly higher
affinity than the longA1 protein that contains VWF residues 1238-1472. Both
proteins contain the VWF A1 domain (residues 1272-1458). Many residues in longA1,
particularly those in the N- and C-terminal sequences flanking the A1 domain, and
in helix alpha1, loops alpha1beta2 and beta3alpha2, demonstrated markedly reduced
HDX compared with their counterparts in shortA1. The HDX-protected region in
longA1 overlaps with the GPIbalpha-binding interface and is clustered with type
2B von Willebrand disease (VWD) mutations. Additional comparison with the HDX of
denatured longA1 and ristocetin-bound longA1 indicates the N- and C-terminal
sequences flanking the A1 domain form cooperatively an integrated autoinhibitory
module (AIM) that interacts with the HDX-protected region. Binding of ristocetin
to the C-terminal part of the AIM desorbs the AIM from A1 and enables longA1
binding to GPIbalpha. Conclusion The discontinuous AIM binds the A1 domain and
prevents it from binding to GPIbalpha, which has significant implications for the
pathogenesis of type 2B VWD and the shear-induced activation of VWF activity.
PMID- 28692143
TI - Ventricular dyssynchrony in pregnant women: A tissue Doppler study.
AB - OBJECTIVE: The aim of the study was to assess the left ventricular (LV)
synchronicity in pregnant women and to identify the main determinants of LV
dyssynchrony in asymptomatic pregnant women. METHODS: One hundred sixty-seven
pregnant women consecutively and 48 age-matched nonpregnant controls were
enrolled. For the assessment of LV systolic dyssynchrony, the standard deviation
of the time from QRS onset to peak systolic (Tps-LV- standard deviation [SD])
velocity and the maximal difference of the time from QRS onset to peak systolic
velocity (Tps-LV) from 12 segments at the apical views. For the LV diastolic
dyssynchrony, the standard deviation of the time from QRS onset to peak diastolic
(Tpe-LV-SD) velocity and the maximal difference of the time from QRS onset to
peak diastolic velocity (Tpe-LV) were calculated. RESULTS: Both systolic and
diastolic dyssynchrony indexes were significantly higher in pregnant women than
in the normal controls (Tps-LV; P<.01, Tps-LV-SD; P<.03, Tpe-LV, P<.05 and Tpe-LV
SD; P<.02). A total of 28 (16.8%) of the pregnant women had a dyssynchrony index
above the accepted value for LV dyssynchrony (>34.4 msec). There was a
significant correlation between LV dyssynchrony indexes with, multiparty,
multifetal pregnancies, systolic blood pressure in pregnant women with LV
dyssynchrony. Additionally LV dyssynchrony was significantly associated with
elevated E/e" and brain natriuretic peptide (BNP). CONCLUSIONS: Both systolic
synchronicity and diastolic synchronicity were affected in pregnant women
compared to nonpregnant women. LV dyssynchrony was significantly correlated with
age, multiparity, and BNP level. Early detectable changes in systolic and
diastolic synchrony may be present in pregnant women at higher risk of peripartum
cardiomyopathy.
PMID- 28692144
TI - Toll-like receptor 1 and 10 gene polymorphisms are linked to postbronchiolitis
asthma in adolescence.
AB - AIM: Toll-like receptors (TLR) are innate immunity molecules and our previous
studies found that TLR1 gene polymorphism was associated with postbronchiolitis
asthma at one to six years of age, as was TLR10 at five to seven years of age.
This study examined any associations at 11-13 years of age. METHODS: This
prospective follow-up study was part of an ongoing evaluation of children
admitted to Tampere University Hospital, Finland, for bronchiolitis in 2001-2004
at less than six months of age. We evaluated the association of TLR1 rs5743618
and TLR10 rs4129009 polymorphisms with asthma and asthma medication in 125
children aged 11-13 years. RESULTS: Associations were measured as adjusted odd
ratios (aOR) with 95% confidence intervals (95% CI). The variant TLR1 rs5743618
(aOR 4.04, 95% CI 0.99-13.01) and TLR10 rs4129009 (aOR 7.02, 95% CI 1.56-31.53)
genotypes increased the risk of needing inhaled corticosteroids (ICSs) at 11-13
years of age. The variant TLR10 genotype (aOR 7.69, 95% CI 1.35-43.95) increased
the risk of persistent asthma continuing from five to seven years of age until 11
13 years of age. The results were similar when the combined genotypes were
analysed. [Correction added on 3 October 2017, after online publication: The data
in the variant TRL1 rs5743618 genotype were incorrect and have been corrected in
this version.] CONCLUSION: Polymorphisms in both the TLR1 and TLR10 genes may
increase the risk of asthma at 11-13 years after infant bronchiolitis.
PMID- 28692145
TI - Efficacy and safety of tiotropium in school-age children with moderate-to-severe
symptomatic asthma: A systematic review.
AB - BACKGROUND: Recently published data support the benefits and safety of the once
daily (OD) long-acting anticholinergic tiotropium bromide bronchodilator for the
treatment of uncontrolled moderate-to-severe asthma in adults and adolescents.
However, its role for the treatment of school-age asthmatics has not yet been
clearly defined. The aim of this systematic review was to assess the efficacy and
safety of tiotropium Respimat(r) in children aged 6-11 years with moderate-to
severe symptomatic asthma. METHODS: Randomized, placebo-controlled trials were
included. Primary outcomes were peak forced expiratory volume in 1 s measured
within 3 h post-dosing) [FEV1 (0-3 h) ] and trough FEV1 measured at the end of
the dosing interval. RESULTS: Three studies (more than 900 patients) were
selected. Tiotropium was associated with significant improvements in FEV1 peak
(mean change from baseline) by 102 mL (P<.0001) and trough by 82 mL (P<.0001)
compared with placebo. Tiotropium 5 MUg dose presented a trend (statistically non
significant) toward a greater bronchodilation in comparison with 2.5 MUg dose.
Tiotropium significantly increased the rate of the Asthma Control Questionnaire
(ACQ-7) responders compared with placebo (82.2% vs 75.4%, number needed to treat
for benefit [NNTB]=15) and significantly decreased the number of patients with at
least one exacerbation in comparison with placebo (29.1% vs. 39.8%, with a NNTB
of 10). There were no significant differences in rescue medication use,
withdrawals, and adverse events. CONCLUSIONS: OD tiotropium Respimat(r) is
efficacious and well tolerated as an add-on to inhaled corticosteroids plus one
or more controller medications in school-age symptomatic asthmatics.
PMID- 28692146
TI - Validation of an algorithm identifying incident primary immune thrombocytopenia
in the French national health insurance database.
AB - OBJECTIVES: To evaluate the accuracy of an algorithm identifying newly diagnosed
immune thrombocytopenia (ITP) patients in the French national health insurance
database (SNIIRAM). METHODS: The source of data was the SNIIRAM of Midi-Pyrenees
region (southwest of France, three million inhabitants). Data of patients with at
least one ITP code (D69.3 code of the International Classification of Disease,
version 10) were extracted between January 1, 2012, and December 31, 2014. We
used an algorithm that identifies newly diagnosed primary ITPs. Medical charts of
incident ITPs were reviewed. Positive predictive values (PPVs) of identification
of true, incident, and primary ITP cases were estimated. RESULTS: Of the 168
patients selected, 161 were true ITP cases yielding a PPV of 95.8% (95%
confidence interval-95% CI: 92.8-98.8). Among them, 128 were truly incident
according to symptom onset date and 134 according to the diagnosis date yielding
PPVs of 79.5% (95% CI: 73.2-85.7) and 83.2% (95% CI: 77.4-89.0), respectively.
Median time between estimated diagnosis date by the algorithm and true diagnosis
date was 0 days (interquartile range: 0 to 15). CONCLUSIONS: This study showed a
very good PPV of this algorithm identifying incident primary ITP patients in the
SNIIRAM.
PMID- 28692147
TI - Persisting hyperbilirubinemia in patients with paroxysmal nocturnal
hemoglobinuria (PNH) chronically treated with eculizumab: The role of
hepatocanalicular transporter variants.
AB - BACKGROUND: Eculizumab-treated paroxysmal nocturnal hemoglobinuria (PNH) patients
(pts) show a dramatic decrease in serum lactate dehydrogenase (LDH) activities
and bilirubin concentrations. However, some pts remain hyperbilirubinemic,
possibly indicating an inadequate response due to extravascular hemolysis.
METHODS: Mutation analyses of hepatocanalicular transporter/nuclear receptor
variants (ABCB4, ABCB11, ATP8B1, NR1H4) were performed in eight (five of eight
males; mean age 38 years [range 26-68 years]) out of the 174 pts with PNH/-clone
at our department due to a persistent increase in total bilirubin concentrations
(median 3.4 mg/dL; range 2.1-8.1 mg/dL) during chronic eculizumab treatment and
normal/or slightly increased serum aminotransferase activities. Median
observation time was 70.1 months (range 10.6-135.2 months). All pts were treated
according to German PNH guidelines. RESULTS: Homozygous and heterozygous
procholestatic variants in the ABCB4, ABCB11, and ATP8B1 genes were identified in
all eight pts. All carried the common ABCB4 c.787A>T polymorphism. The A(TA)7 TAA
variant in the UGT1A1 promoter causing Gilbert syndrome was detected in three pts
(5/8). CONCLUSIONS: Hyperbilirubinemia in PNH pts treated with eculizumab might
not only be due to an insufficient response but rather a combination of mutations
in hepatocanalicular transporter variants, Gilbert syndrome, and extravascular
hemolysis. Our findings warrant further studies concerning transporter and enzyme
variants in PNH to determine their clinical significance.
PMID- 28692148
TI - Terminal blades in Macrocystis and their unexplored links to functional biology.
PMID- 28692149
TI - Animal models of human type 1 diabetes for evaluating combination therapies and
successful translation to the patient with type 1 diabetes.
AB - Animal models of human type 1 diabetes will be of a great importance for the
evaluation of new combination therapies with curative potential. However,
reliable predictive power for successful translation to patients with type 1
diabetes is crucial. This will be particularly important in the future when
evaluating success of new combination therapies that show great promise for
preservation and restoration of beta cell mass and thereby reverse the type 1
diabetic hyperglycaemia. But not all spontaneous animal models are equally well
suited for this purpose. The advantages and disadvantages of the three
spontaneous rat models (BioBreeding diabetes-prone [BB] rat, Komeda [KDP] rat,
and LEW.1AR1-iddm [IDDM] rat) as well as the NOD mouse, compared with the
characteristics of human type 1 diabetes, are considered in this review.
PMID- 28692150
TI - Acidity Strength of Solid Catalysts Probed by Hyperpolarized Natural Abundance 17
O NMR Spectroscopy.
AB - Observation of Bronsted acid sites: By enhancing the solid-state NMR signals of
17 O at natural abundance with dynamic nuclear polarization (DNP), Pruski et al.
were able to measure oxygen-proton distances accurately with sub-picometer
precision. The results give insight into the Bronsted acidity of a range of solid
acid catalysts.
PMID- 28692151
TI - Towards a quantitative definition of plant hormone sensitivity.
AB - A definition of plant hormone sensitivity is proposed which is based on the
initial rates of responses at different hormone concentrations. By analogy with
enzyme kinetics, it is concluded that simple concentration-response curves can be
described by a function containing three 'sensitivity parameters'. Objective
methods for determining the values of these parameters and for comparing curves
are described. These methods are used to describe the responses of Commelina
communis L. stomata to abscisic acid. If certain assumptions are valid, the
sensitivity parameters can be assigned physicochemical meanings. To validate the
assumptions, certain experimental criteria must be fulfilled and these are
discussed.
PMID- 28692152
TI - Suberin lamellae in the hypodermis of maize (Zea mays) roots; development and
factors affecting the permeability of hypodermal layers.
AB - The development of suberin lamellae in the hypodermis of Zea mays cv. LG 11 was
observed by electron microscopy and the presence of suberin inferred from
autoliuorescence and by Sudan black B staining in nodal (adventitious) and
primary (seminal) root axes. Suberin lamellae were evident at a distance of 30-50
mm from the tip of roots growing at 20 degrees C and became more prominent with
distance from the tip. Both oxygen deficiency and growth at 13 degrees C produced
shorter roots in which the hypodermis was suberized closer to the root tip. There
were no suberin lamellae in epidermal cells or cortical collenchyma adjacent to
the hypodermis. Plasmodesmata were not occluded by the suberin lamellae: there
were twice as many of them in the inner tangential hypodermal wall (1,14 MUn-2 )
as in the junction between the epidermis and hypodermis (0.54 MUm-2 ). Water
uptake by seminal axes (measured by micropotometry) was greater at distances more
than 100 mm from the root lip than in the apical zone where the hypodermis was
unsuberized. In the more mature zones of roots grown at 13 degrees C rates of
water uptake were greater than in roots grown at 20 degrees C even though
hypodermal suberization was more marked. Sleeves of epidermal/hypodermal cells
(plus some accessory collenchyma) were isolated from the basal 60 mm of nodal
axes by enzymatic digestion (drisclase). The roots were either kept totally
immersed in culture solution or had the basal 50 mm exposed to moist air above
the solution surface. In both treatments the permeabilities to tritiated water
and 86 Rb were low (circa 10-5 mms-1 ) in sleeves isolated from the extreme base.
In roots grown totally immersed, however, the permeability of sleeves increased
10 to 50-fold over a distance of 40 mm. In roots exposed to moist air the
permeability remained at a low level until the point where the root entered the
culture solution and then increased rapidly (> 50-fold in a distance of 8 mm).
Growth of roots in oxygen depleted (5% O2 ) solutions promoted the development of
extensive cortical aerenchymas. These developments were not associated with any
reduction in permeability of sleeves isolated from the basal 40 mm of the axis.
It was concluded that the presence of suberin lamellae in hypodermal walls does
not necessarily indicate low permeability of cells or tissues to water or
solutes. The properties of the walls (lamellae?) can be greatly changed by
exposure to moist air, perhaps due to increased oxygen availability.
PMID- 28692153
TI - Changes in hydraulic conductance of citrus trees following a reduction in wetted
soil volume.
AB - The effcct of the transition from fully to partially wetted soil voluine on
transpiration rate and hydraulic conductance of mature citrus trees was examined
in a 23-year-old, coninicrcial, sprinklerirrigated, Shanio u t i orange orchard.
I rriga t i on frequency was determined by the rate of water loss from the soil,
a s measured by neutron probes. The hydraulic conductance of tlic tree was
coniputed from the rclationship between sap flow i n the trunk and leaf water
potential. The diurnal valucs of leaf water potential and sap flow shifted
towards lower levels as tlie water stored in the root zone was depleted. In the
fully wetted soil volume the tree hydraulic conductance remained constant
throughout the irrigation period, from June to Novcniber. However, partial
wetting of the soil volume (40%) caused a reduction in the hydraulic conductance
of the tree. Tlie decreased hydraulic conductance is attributed to tlie permanent
interruption of water transport in part of tlie root system. Tlie rcsults of tlie
experiment suggest that despite tlie increase of irrigation frequency, partial
wetting intensifies water stress in tlie trees.
PMID- 28692154
TI - Salt tolerance in Aster tripolium L. III. Na and K fluxes in intact seedlings.
AB - Uptake and transport of Na and K was studied using the radioactive tracers 22 Na
and 42 K in intact Aster tripolium L. seedlings grown at two salinities CS 10 and
CS 100, (containing 10mol m-1 and 100 mol m-3 Na, respectively, together with
other major ions in the proportions found in sea water). At both salinities a
much greater proportion of the Na than K taken up by the plant was subsequently
transported to the shoot. Most 42 K fluxes were reduced by about 40% in CS 100
plants relative to CS 10 except root accumulation which increased. Experiments
involving changing the salinity from CS 10 to CS 100 showed that 42 K fluxes
remained constant for at least 40 h, indicating that competition with Na for
uptake sites was not the cause of the reduced flux in CS 100 plants. 22 Na fluxes
responded immediately to a change in salinity with all fluxes increasing six-fold
when the salinity was raised. When the salinity was lowered, however, root
accumulation returned to the level in CS 10 control plants whereas transport to
the shoot was inhibited by the previous high salinity treatment, being reduced to
only 35% of the rate in CS 10 plants. The time courses of osmotic adjustment and
Na accumulation following an increase in salinity were found to be very similar,
with sufficient Na being accumulated to account for the observed increase in sap
osmotic pressure.
PMID- 28692155
TI - Lead accumulation and its translocation barriers in roots of Allium cepa L.
autoradiographic and ultrastructural studies.
AB - Lead migrating through the tissues of Allium cepa L. was found, by electron
microscopy, autoradiography and other methods, to encounter at least three
barriers to penetration. The layers of protoderm and hypodermic meristematic
cells in the root meristematic zone and the layer of endodermis in the mature
root zone were barriers to apoplastic transport. The central zone was a barrier
to apoplastic and symplastic transport. It comprises the quiescent centre in the
root meristem and the central part of the root cap. The cells of the deepest
ground meristematic tissue layers seemed to act as a barrier, which keeps lead
away from the procambium. Lead accumulated in roots but it was not uniformly
distributed between their various tissues. The largest amount of lead accumulated
both in ground meristematic and cortex tissues.
PMID- 28692156
TI - Cation exchange in isolated xylem cell walls of tomato. I. Cd2+ and Rb+ exchange
in adsorption experiments.
AB - Purified xylem cell walls were prepared from isolated xylem bundles of tomato (an
inbred line of Lycopersicon esculentum Mill, cv. Tiny Tim). Adsorption and
exchange experiments were carried out with 115 Cd2+ , 82 Rb+ and 82 Br- . The
application of gamma-ray spectroscopy permitted the simultaneous measurement of
several ions applied together. The cell-wall water volume was shown to be
independent of the external pH and solution ionic strength, possibly due to the
presence of lignin. The Donnan Free Space (DFS) volume could be determined as a
constant 0.15 dm3 per kg cell-wall dry weight. Consequently, the total cell-wall
cation exchange capacity (CEC) could be estimated based on the DFS volume, and
amounted to approximately 1000 mol m-3 negative charges. The results of Cd2+ -Rb+
exchange experiments indicated an apparent CEC value of about 350-450 mol m-3
DFS, at external pH ~ 4. These data are in agreement with earlier reports on
xylem wall CEC, and indicate the weak acid characteristics of the charge groups.
The rational selectivity coefficient RCdRb , of the cell wall was shown to depend
on external ion fractions and ionic strength, with a maximum RCdRb of 450 at
ionic Cd2+ fraction near 0.3, based at the smallest experimental ionic strength
of the external solution. The adsorption of Cd2+ , applied at relatively high
concentrations, was shown to be stimulated by simultaneous application of high
Rb+ concentrations.
PMID- 28692157
TI - Photosynthetic responses to salinity in two clones of Agrostis stolonifera.
AB - The response of photosynthesis, Fe , to salinity was examined in two clones of
Agrostis stolonifera, one derived from a salt marsh (SM) and the other from an
inland site (IL). The response of young and old leaves was examined over one week
of salt treatment and changes in leaf water relations and concentrations of Na+ ,
Cl- and K+ ions were also monitored. Sodium+ and chloride- concentrations rose
much more sharply in the older leaves of both clones and Fe declined to ca. zero
by Day 4. Fe in the young leaves of the SM clone was unaffected by salt whilst
the young leaves of the IL clone showed a 20% reduction in Fe within 24 h of salt
application. This decline was due to a decline in stomatal conductance and a
reduction in the photosynthetic capacity of the mesophyll and was associated with
a greater accumulation of Na+ and Cl- ions and loss of K+ ions than in the SM
clone. The significance of the salt exclusion from the young leaves of the SM
clone to its growth on the salt marsh is discussed.
PMID- 28692158
TI - Hydraulic flow characteristics in the lignotuberous mallee Eucalyptus behriana F.
Muell. in the field.
AB - The lignotuberous mallee Eucalyptus behriana F. Muell, had much lower predawn
leaf water potentials (not higher than - 1.2MPa) than other eucalypts (as high as
- 0.2MPa), even after extended rain. This led to the expectation that the
lignotuber of E. behriana might have specific hydraulic characteristics. Keeping
the soil around partially defoliated mallces for several days underwater did not
raise the water status above the maximum leaf water potential observed under
natural conditions. Digging a plant out and placing its roots in water after
removal of the soil rapidly increased the water status to a level consistant with
other eucalypts. This indicated that the major impedance to water uptake was a
component of the soil rather than in the roots or in the lignotuber. Some of the
individual mallces had only two major stems or branches. One stem or branch was
kept covered throughout the experiments to prevent transpiration. The other stem
was subjected to a variety of different conditions in order to modify water loss
from it. The transpiring branch affected the water status of the non-transpiring
plant parts. Hydraulic resistances in the shoot and root/lignotuber were
determined from differences in the leaf water potential of covered and uncovered
branches, at high water flow rates through the plant. Resistances in branches,
including the liquid phase component of the leaf, were significantly larger than
in root or lignotuber. The total plant hydraulic resistance of E. behriana was
similar to that of other eucalypts, such as E. pauciflora Sieb. ex Spreng. or E.
delegatensis R. T. Bak., even though its growth form was different and its
natural leaf water potentials were much lower. An osmotic adjustment at the leaf
level was observed in the mallee, keeping its bulk leaf turgor in the same range
as compared to the other eucalypt species.
PMID- 28692159
TI - Salt tolerance in Aster tripolium L. II. Ionic regulation.
AB - Measurements of tissue ion contents (Na, K and Cl) were carried out at frequent
intervals on plants of Aster tripolium L. grown at a range of salinities for 36
d. Aster tripolium behaved as a typical halophyte showing high levels of
inorganic ion accumulation even at low salinities. As salinity increased Na
replaced K to a large extent in the shoot but root K was unaffected up to 500 mol
m-3 external NaCl. Shoot (Na + K) concentration on a tissue water basis was
maintained constant in all treatments throughout the experiment, whereas shoot
(Na + K) on a dry weight basis showed marked fluctuations in some treatments. An
increase in (Na + K) per gram dry weight was, however, accompanied by a parallel
increase in fresh weight: dry weight (FW : DW) ratio. Transport of (Na + K) to
the shoot per unit root weight changed during the experiment in the manner
expected, given the observed changes in shoot relative growth rate and FW : DW to
result in a constant shoot (Na + K) concentration on a water basis. Chloride was
the major balancing anion in the shoot at high salinity, but never accounted for
more than 38% of the (Na + K) found in the root tissue. At all salinities (Na +
K) salts accounted for the majority of the measured shoot sap osmotic potential.
The interactions between salinity, growth, ion transport and osmotic adjustment
are discussed.
PMID- 28692160
TI - Translatable mRNA changes in ethylene induced abscission zones of Phaseolus
vulgaris (Red Kidney).
AB - The wheat germ translation system was programmed with soluble RNA extracted from
foliar abscission zones of Phaseolus vulgaris, These extracts were taken at
various times after the induction of abscission. A translation product with a
molecular weight of 42 kilodalton (kD) was only present after this treatment,
though three other species 32, 27 and 17 kD increased substantially. The isozyme
of cellulase with a pi of 9.5 could not be conclusively identified amongst the
products though the 32 kD protein is probably chitinase. Comparison of the
abscission zone translatable RNA with that from adjacent petiole and stem tissues
showed the 17 kD protein developed in all these location. The 42, 32 and 27 kD
bands were found predominantly in the zone and petiole.
PMID- 28692161
TI - Electron microscopic structure and oxygen evolution activity of thylakoids from
Avicennia marina prepared under different osmotic and ionic conditions.
AB - Stacking of thylakoid membranes in vitro was assessed using electron microscopy.
Grana stacks of spinach thylakoids formed when 5 mol m-3 MgCl2 was present, but
no stacking of thylakoids from the mangrove Avicennia marina occurred in the
presence of 10 mol m-3 ? MgCl2 . Isolation of mangrove thylakoids with a high
osmotic strength medium did not induce grana formation if the medium consisted
only of sorbitol or glycinebetaine. Addition of cations to the high osmotic
strength medium did induce some loose-grana formation, with divalent cations
being more effective than monovalent cations. Glycinebetaine was a better
osmoticum than sorbitol for grana formation provided divalent cations had been
added. Oxygen evolution activity of the preparations was influenced by the amount
of membrane stacking, with the preparations with the greatest amount of stacked
membrane having the highest activity. Isolation with sorbitol or glycinebetaine
based media did not alter this pattern, nor did assay in sorbitol or
glycinebetaine. Mangrove thylakoids have a requirement for both a high osmotic
strength and divalent cations for grana formation in vitro which may be related
to the low water potential of the plant environment in vivo.
PMID- 28692162
TI - Salt tolerance in Aster tripolium L. I. The effect of salinity on growth.
AB - A study of the growth of the maritime halophyte Aster tripolium L. has been
carried out over a range of salinity treatments. The regression approach to
growth analysis using frequent small harvests has been used to allow 'continuous'
measurement of growth over a period of 36 d. Salinity was applied with the major
ions present in ratios typical of those found in seawater. Growth was inhibited
in terms of both dry weight production and leaf expansion at salinity levels
equivalent to 0.625 strength sea water (full culture solution 300) and above,
with the greatest effect being seen in terms of leaf area. Aster tripolium did
not show increased succulence at high salinity, leaf fresh weight to dry weight
ratio in fact declined, whilst leaf fresh weight per unit area remained constant.
It should be noted that the plants exhibit low growth rates due to the low light
intensity used.
PMID- 28692163
TI - Pretreatment with melatonin protects against cyclophosphamide-induced oxidative
stress and renal damage in mice.
AB - Cyclophosphamide (CP) is widely used in treatment of different cancers.
Nephrotoxicity is one of the dose-limiting side effects of CP. This study was
carried out to investigate the effect of melatonin (MEL) on CP-induced
nephrotoxicity in mice. In this study, 50 Swiss albino mice (20-25 g) were
randomly divided into five groups. Mice were pretreated with MEL
intraperitoneally (i.p) in doses of 5, 10 and 20 mg/kg for five consecutive days,
and CP (200 mg/kg, i.p) was administrated on the 5th day 1 h after the last dose
of MEL. Then on day 6, blood samples were collected to determine serum creatinine
(Cr) and blood urea nitrogen (BUN) levels. The kidneys were used for histological
examination, biochemical assays and real-time PCR studies. Malondialdehyde (MDA),
glutathione (GSH), protein carbonyl (PC), nitric oxide (NO) level, catalase
(CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx) and
myeloperoxidase (MPO) activity were assessed in renal tissue. In addition, the
expression of SOD2 and PGx1 was measured using real-time PCR method in renal
tissue. Results showed that CP administration significantly increases Cr, BUN,
MDA, PC, NO level and MPO activity. It also decreases renal GSH level, SOD, GPx
and CAT activity. Pretreatment with MEL (especially 20 mg/kg, i.p.) for 5 days
prevented these changes; however, it did not affect the SOD activity. Our results
revealed that MEL might be useful for prevention of the nephrotoxicity induced by
CP through ameliorative effects on biochemical indices and oxidative stress
parameters.
PMID- 28692164
TI - Studying women who don't make best use of antenatal care.
PMID- 28692166
TI - Sodium intake, sodium excretion, and cardiovascular risk: involvement of genetic,
hormonal, and epigenetic factors.
PMID- 28692165
TI - Clinical and prognostic significance of a reverse dipping pattern on ambulatory
monitoring: An updated review.
AB - Reverse or inverted dipping (ie, the phenomenon characterized by higher nighttime
compared with daytime blood pressure values) is an alteration of circadian blood
pressure rhythm frequently documented in hypertension, type 2 diabetes mellitus,
chronic kidney disease, and sleep apnea syndrome, and generally regarded as a
harmful condition. Available literature on the clinical and prognostic
implications of reverse dipping is scanty. The present article will review a
number of relevant issues concerning reverse dipping, in particular: (1) its
possible mechanisms; (2) prevalence and clinical correlates, (3) concomitant
cardiac and extracardiac subclinical organ damage; (4) association with acute and
chronic cardiovascular diseases; (5) prognostic value in predicting
cardiovascular events and mortality; and (6) therapeutic interventions aimed at
reverting this abnormal circadian blood pressure rhythm.
PMID- 28692167
TI - Modern management of hypertensive emergencies and urgencies: Do we need more
technology, paramedics, or physicians?
PMID- 28692168
TI - Indirect effects of ecosystem engineering combine with consumer behaviour to
determine the spatial distribution of herbivory.
AB - Ecosystem engineers alter environments by creating, modifying or destroying
habitats. The indirect impacts of ecosystem engineering on trophic interactions
should depend on the combination of the spatial distribution of engineered
structures and the foraging behaviour of consumers that use these structures as
refuges. In this study, we assessed the indirect effects of ecosystem engineering
by a wood-boring beetle in a neotropical mangrove forest system. We identified
herbivory patterns in a dwarf mangrove forest on the archipelago of Twin Cays,
Belize. Past wood-boring activity impacted more than one-third of trees through
the creation of tree holes that are now used, presumably as predation or thermal
refuge, by the herbivorous mangrove tree crab Aratus pisonii. The presence of
these refuges had a significant impact on plant-animal interactions; herbivory
was more than fivefold higher on trees influenced by tree holes relative to those
that were completely isolated from these refuges. Additionally, herbivory
decreased exponentially with increasing distance from tree holes. We use
individual-based simulation modelling to demonstrate that the creation of these
herbivory patterns depends on a combination of the use of engineered tree holes
for refuge by tree crabs, and the use of two behaviour patterns in this species
site fidelity to a "home tree," and more frequent foraging near their home tree.
We demonstrate that understanding the spatial distribution of herbivory in this
system depends on combining both the use of ecosystem engineering structures with
individual behavioural patterns of herbivores.
PMID- 28692169
TI - The relationship between anxiety and quality of life in children with hereditary
angioedema.
AB - BACKGROUND: The severe life-threatening characteristics of hereditary angioedema
(HAE) with C1-inhibitor deficiency (C1-INH-HAE) can affect anxiety levels among
pediatric patients. This emotional burden together with the physical restrictions
of C1-INH-HAE may decrease children's health-related quality of life (HRQoL).
OBJECTIVES: (i) To compare anxiety state and trait between children with C1-INH
HAE and healthy controls; (ii) to examine the relationship between the level of
anxiety of children with C1-INH-HAE, their disease activity/affected sites and
their HRQoL; and (iii) to predict the HRQoL of children with C1-INH-HAE based on
their anxiety level and disease activity/affected sites METHODS: Thirty-three
children with C1-INH-HAE (aged 5-18 years) and 52 healthy controls were recruited
from Israel and Hungary. All children completed the State-Trait Anxiety Inventory
for Children (STAIC), the Pediatric Quality of Life Inventory (Peds-QL)
demographic questionnaire and a disease activity and site questionnaire . Disease
activity was defined as the number of attacks in last year. RESULTS: Both anxiety
state and trait were significantly higher among children with C1-INH-HAE as
compared to the controls (44.74+/-10.56 vs 38.76+/-10.67, P<.01, 29.21+/-5.16 vs
25.23+/-4.09, P<.001 in comparison). Significant differences were found between
C1-INH-HAE patients with HAE attacks, asymptomatic C1-INH-HAE patients, and
healthy controls in both anxiety state (F56,2 =4.69, P=.001) and trait (F56,2
=9.06, P<.0001). A higher anxiety trait was correlated with the number of
angioedema-affected sites (r=.52, P=.003). The presence of HAE attacks and higher
anxiety trait predicted a lower HRQoL in children with C1-INH-HAE. CONCLUSIONS:
C1-INH-HAE children have higher anxiety trait and state, which correlate with
reduced HRQoL domains.
PMID- 28692170
TI - Expulsions and adverse events following immediate and later insertion of a
levonorgestrel-releasing intrauterine system after medical termination of late
first- and second-trimester pregnancy: a randomised controlled trial.
AB - OBJECTIVES: To compare expulsions and adverse events (AEs) between immediate and
delayed insertion of a levonorgestrel-releasing intrauterine system (LNG-IUS)
following medical termination of pregnancy (MTOP). DESIGN: Randomised controlled
trial. SETTING: Helsinki University Hospital, Finland, January 2013-December
2014. POPULATION: Cohorts of 102 (gestational age 64-84 days, late first
trimester) and 57 (gestational age 85-140 days, second trimester) women
requesting MTOP and LNG-IUS contraception. METHODS: LNG-IUS insertion occurred
immediately (same day) or 2-4 weeks following MTOP. Follow-up visits were at 2-4
weeks, 3 months, and 1 year. MAIN OUTCOME MEASURES: LNG-IUS expulsion by 3 months
and 1 year. AEs and bleeding profiles within 3 months. RESULTS: Following late
first-trimester MTOP the LNG-IUS expulsion rates by 3 months were 14 (27.5%) in
the immediate-insertion group and two (4.0%) in the delayed-insertion group (risk
ratio, RR 6.86; 95% confidence interval, 95% CI 1.64-28.66). By 1 year the
expulsion rates were 17 (33.3%) and six (12.0%) (RR 2.78, 95% CI 1.19-6.47).
Following second-trimester MTOP LNG-IUS expulsion rates by 3 months and 1 year
were five (18.5%) in the immediate-insertion group and one (3.6%) in the delayed
insertion group (RR 5.19, 95% CI 0.65-41.54). No differences in AEs and bleeding
profiles emerged between the groups. CONCLUSIONS: Immediate LNG-IUS insertion
after late first- or second-trimester MTOP is feasible, does not increase the
complication rate, or alter the uterine bleeding patterns; however, immediate
insertion increased the expulsion rate, which may limit the cost-effectiveness.
TWEETABLE ABSTRACT: Immediate insertion of LNG-IUS following MTOP at 9-20 weeks
of gestation is feasible and safe.
PMID- 28692171
TI - What is your diagnosis? Aspirate from a digit of a dog.
PMID- 28692172
TI - Effect of monthly high-dose vitamin D on bone density in community-dwelling older
adults substudy of a randomized controlled trial.
AB - BACKGROUND: Severe vitamin D deficiency causes osteomalacia, yet trials of
vitamin D supplementation in the community have not on average demonstrated
benefit to bone mineral density (BMD) or fracture risk in adults. OBJECTIVE: To
determine whether monthly high-dose vitamin D supplementation influences BMD in
the general population and in those with low 25-hydroxyvitamin D levels. METHODS:
Two-year substudy of a trial in older community-resident adults. A total of 452
participants were randomized to receive monthly doses of vitamin D3 100 000 IU,
or placebo. The primary end-point was change in lumbar spine BMD. Exploratory
analyses to identify thresholds of baseline 25-hydroxyvitamin D for vitamin D
effects on BMD were prespecified. RESULTS: Intention-to-treat analyses showed no
significant treatment effect in the lumbar spine (between-groups difference
0.0071 g cm-2 , 95%CI: -0.0012, 0.0154) or total body but BMD loss at both hip
sites was significantly attenuated by ~1/2% over 2 years. There was a significant
interaction between baseline 25-hydroxyvitamin D and treatment effect (P = 0.04).
With baseline 25-hydroxyvitamin D <= 30 nmol L-1 (n = 46), there were between
groups BMD changes at the spine and femoral sites of ~2%, significant in the
spine and femoral neck, but there was no effect on total body BMD. When baseline
25-hydroxyvitamin D was >30 nmol L-1 , differences were ~1/2% and significant
only at the total hip. CONCLUSIONS: This substudy finds no clinically important
benefit to BMD from untargeted vitamin D supplementation of older, community
dwelling adults. Exploratory analyses suggest meaningful benefit in those with
baseline 25-hydroxyvitamin D <= 30 nmol L-1 . This represents a significant step
towards a trial-based definition of vitamin D deficiency for bone health in older
adults.
PMID- 28692173
TI - Perinatal and maternal morbidity and mortality among term singletons following
midcavity operative vaginal delivery versus caesarean delivery.
AB - OBJECTIVE: To quantify severe perinatal and maternal morbidity/mortality
associated with midcavity operative vaginal delivery compared with caesarean
delivery. DESIGN: Population-based, retrospective cohort study. SETTING: British
Columbia, Canada. POPULATION: Term, singleton deliveries (2004-2014) by attempted
midcavity operative vaginal delivery or caesarean delivery in the second stage of
labour, stratified by indication for operative delivery (n = 10 901 deliveries;
5057 indicated for dystocia, 5844 for fetal distress). METHODS: Multinomial
propensity scores and mulitvariable log-binomial regression models were used to
estimate adjusted rate ratios (ARR) and 95% confidence intervals (95% CI). MAIN
OUTCOME MEASURES: Composite severe perinatal morbidity/mortality (e.g.
convulsions, severe birth trauma and perinatal death) and severe maternal
morbidity (e.g. severe postpartum haemorrhage, shock, sepsis and cardiac
complications). RESULTS: Among deliveries with dystocia, attempted midcavity
operative vaginal delivery was associated with higher rates of severe perinatal
morbidity/mortality compared with caesarean delivery (forceps ARR 2.11, 95% CI
1.46-3.07; vacuum ARR 2.71, 95% CI 1.49-3.15; sequential ARR 4.68, 95% CI 3.33
6.58). Rates of severe maternal morbidity/mortality were also higher following
midcavity operative vaginal delivery (forceps ARR 1.57, 95% CI 1.05-2.36; vacuum
ARR 2.29, 95% CI 1.57-3.36). Among deliveries with fetal distress, there were
significant increases in severe perinatal morbidity/mortality following attempted
midcavity vacuum (ARR 1.28, 95% CI 1.04-1.61) and in severe maternal morbidity
following attempted midcavity forceps delivery (ARR 2.34, 95% CI 1.54-3.56).
CONCLUSION: Attempted midcavity operative vaginal delivery is associated with
higher rates of severe perinatal morbidity/mortality and severe maternal
morbidity, though these effects differ by indication and instrument. TWEETABLE
ABSTRACT: Perinatal and maternal morbidity is increased following midcavity
operative vaginal delivery.
PMID- 28692174
TI - Effects of pyriproxyfen on wild populations of the housefly, Musca domestica, and
compatibility with its principal parasitoids.
AB - BACKGROUND: The housefly, Musca domestica L., is an important pest of animal
agriculture. Effective fly management requires integration of manure management,
mass trapping, biological control, and selective insecticide use. Insecticidal
control of houseflies is difficult due to the rapidity of resistance development,
yet the insect growth regulator pyriproxyfen (PPF) is one of few insecticides
that may still be effective. Here, we tested the susceptibility of wild housefly
populations in the USA and in Israel to PPF, as well as the effect of PPF on
housefly parasitoids of the genera Muscidifurax and Spalangia. RESULTS: Most
housefly populations from both countries were completely eliminated at PPF
concentrations of 100 mg kg-1 (USA) and 600 mg kg-1 (Israel). One population from
each country exhibited initial levels of PPF tolerance. PPF efficacy
significantly decreased in cow manure. Emergence rates of parasitoids developing
in PPF-treated hosts at concentrations of >=600 mg kg-1 were significantly
affected, whereas other fitness parameters were moderately to non-affected.
CONCLUSIONS: PPF is still an effective tool for housefly control, but resistance
management practices should be employed to avoid resistance. PPF is compatible
with principal housefly parasitoids at concentrations <600 mg kg-1 , and is
suitable for use in integrated pest management. (c) 2017 Society of Chemical
Industry.
PMID- 28692175
TI - Neurosonology Accuracy for Isolated Acute Vestibular Syndromes.
AB - OBJECTIVES: The clinical approach to acute vestibular syndromes is often complex
for the physician. Neurosonology offers a noninvasive method to study the
cervicocephalic circulation when a vascular etiology is suspected. We aim to
evaluate the diagnostic accuracy of a vascular neurosonological exam in isolated
acute vestibular syndrome. METHODS: All patients submitted to cerebrovascular
ultrasound and magnetic resonance imaging during the period between 2011 and 2015
with acute isolated vestibular syndrome. Those with any clinical sign of
brainstem lesion on presentation were excluded. All patients performed the
neuroimaging study (brain computed tomography and magnetic resonance imaging) and
neurologic surveillance. Neurosonological exam included all intra- and
extracranial segments of the vertebrobasilar circulation. Positive ultrasound
exam was defined as the presence of stenotic or occlusive disease in any of these
segments related to the infarcted area. RESULTS: A total of 108 patients were
included: 60 (53.6%) were males (mean age: 60.75 years (standard deviation,
14.17)). In 27 patients (25.0%) a cerebral ischemic lesion was found to be the
cause of the vertigo. Neurosonological assessment showed a sensitivity of 40.7%
(95% confidence interval (CI): 22.4; 61.2), specificity of 100% (95% CI: 95.5;
100.0), positive predictive value (PPV) of 100% (95% CI: 71.5; 100.0), and
negative predictive value (NPV) of 83.5% (95% CI: 74.6; 90.3). CONCLUSIONS: Our
study suggests that cerebrovascular ultrasound is a highly specific method for
the diagnosis of cerebrovascular vertigo. However, its low sensitivity makes it a
poor candidate for screening.
PMID- 28692176
TI - Phenotypic spectrum associated with de novo mutations in QRICH1 gene.
AB - Rare de novo mutations represent a significant cause of idiopathic developmental
delay (DD). The use of next-generation sequencing (NGS) has boosted the
identification of de novo mutations in an increasing number of novel genes. Here
we present 3 unrelated children with de novo loss-of-function (LoF) mutations in
QRICH1, diagnosed through trio-based exome sequencing. QRICH1 encodes the
glutamine-rich protein 1, which contains 1 caspase activation recruitment domain
and is likely to be involved in apoptosis and inflammation. All 3 children had
speech delay, learning difficulties, a prominent nose and a thin upper lip. In
addition, 2 of them had mildly raised creatine kinase (CK) and 1 of them had
autism. Despite their small number, the patients had a relatively consistent
pattern of clinical features suggesting the presence of a QRICH1-associated
phenotype. LoF mutations in QRICH1 are suggested as a novel cause of DD.
PMID- 28692177
TI - Age-related off-label use of nasal corticosteroids for allergies is relatively
common in Finnish children with asthma.
AB - AIM: Allergies can worsen asthma symptoms and we used national data to identify
allergy medication prescribed for Finnish children and adolescents who used
asthma medication. METHODS: Register data were available for 13 435 Finnish
children aged 0-17 who were entitled to special reimbursement for asthma
medication during 2006-2009. Allergy medication purchases were individually
analysed 2 years before and 2 years after the entitlement for asthma medication
reimbursement was granted. RESULTS: Two-thirds (66.5%) of the children had used
at least one allergy medication during the 4-year follow-up, with an average of
five purchases. Most (91%) of the allergy medication purchased was systemic
antihistamines and half (50%) was nasal corticosteroids. In all, 8% of the
allergy medication and 22% of the nasal corticosteroids were classified as off
label purchases based on the child's age. Paediatric allergologists and
paediatricians prescribed 59% of the allergy medication and 76% of the off-label
nasal corticoids. CONCLUSION: Most asthmatic children and adolescents used
allergy medication. Nasal corticosteroids were the commonly prescribed off-label
item and the prescribers were mainly specialists in paediatric allergology or
paediatrics. Official dosage instructions and more specific clinical guidelines
are needed to support appropriate prescribing of nasal corticosteroids for young
children.
PMID- 28692178
TI - Cell-free DNA - Minimally invasive marker of hematological malignancies.
AB - Although tumor cells are the most reliable source of tumor DNA, biopsy of the
tumor is an invasive procedure that should be avoided in some cases. The main
limitation of any biopsy is sampling of one tumor site, which may not represent
all malignant clones due to the heterogeneity of the tumor. These clones respond
to treatment differently and thus directly influence survival of the patient.
Circulating cell-free DNA (cfDNA) is released from multiple tumor sites, reflects
overall heterogeneity of the tumor, and correlates with its progression.
Detection of tumor-specific genetic and epigenetic aberrations in cfDNA could
have a direct impact on molecular diagnosis, prognosis, follow-up of disease,
monitoring of minimal residual disease, and response to treatment. While most
cfDNA data are still experimental, they are very promising. This review focuses
on cfDNA in hematological malignancies.
PMID- 28692179
TI - Differences in growth of Canadian children compared to the WHO 2006 Child Growth
Standards.
AB - BACKGROUND: To evaluate if there are departures from the WHO Child Growth
Standards (WHO-CGS) in postnatal growth of healthy 'Canadian' children in Ontario
up to age 2 years, including by infant feeding and ethnicity. METHODS: We
included data on 9964 healthy, singleton children born in Ontario, Canada.
Smoothed weight, length and body mass index (BMI) percentile curves were
generated using quantile regression for the Canadian cohort from birth to age 2
years. Differences in percentile values were calculated comparing Canadian
children vs. the WHO-CGS. RESULTS: Canadian children under age 2 years were
longer than the WHO-CGS at the 10th (0.8 cm), 50th (1.3 cm) and 90th (1.9 cm)
percentiles. Canadian children incrementally surpassed the WHO-CGS in weight
after age 6 months, and in BMI after 9 months. By age 2 years, the 50th
percentile weight of Canadian males was 823 g (95% confidence interval (CI) 680,
965) higher than the WHO-CGS 50th percentile. Weight differences were seen
regardless of feeding practice, and were greatest among children of mothers born
in Canada and Europe/Western nations, and least for those of East Asian/Pacific
or South Asian heritage. Among Canadian breastfed males, 18% (95% CI 16, 19) of
newborns and 26% (95% CI 20, 33) toddlers aged 2 years were classified by WHO-CGS
as weighing >90th percentile - much higher than the expected rate of 10%.
Similarities were seen for differences in BMI. CONCLUSIONS: Healthy Canadian
infants/toddlers are longer and heavier than the WHO-CGS norms. Explanations for
these discrepancies require further elucidation.
PMID- 28692181
TI - Time to test tamponade.
PMID- 28692180
TI - Loss of SRY-box2 (SOX2) expression and its impact on survival of patients with
oesophageal adenocarcinoma.
AB - BACKGROUND: Oesophageal adenocarcinoma (OAC) is a highly aggressive malignancy
with poor survival, which is highly variable amongst patients with comparable
conventional prognosticators. Therefore molecular biomarkers are urgently needed
to improve the prediction of survival in these patients. SRY (sex determining
region Y)-box 2, also known as SOX2, is a transcription factor involved in
embryonal development of the gastrointestinal tract as well as in carcinogenesis.
The purpose of this study was to see whether SOX2 expression is associated with
survival in patients with OAC. METHODS: SOX2 was studied by immunohistochemistry
in patients who had undergone potentially curative oesophagectomy for
adenocarcinoma. Protein expression of SOX2 was evaluated using tissue microarrays
from resection specimens, and results were analysed in relation to the clinical
data by Cox regression analysis. SOX2 was evaluated in two independent OAC
cohorts (Rotterdam cohort and a multicentre UK cohort). RESULTS: Loss of SOX2
expression was independently predictive of adverse overall survival in the
multivariable analysis, adjusted for known factors influencing survival, in both
cohorts (Rotterdam cohort: hazard ratio (HR) 1.42, 95 per cent c.i. 1.07 to 1.89,
P = 0.016; UK cohort: HR 1.54, 1.08 to 2.19, P = 0.017). When combined with
clinicopathological staging, loss of SOX2 showed an increased effect in patients
with pT1-2 tumours (P = 0.010) and node-negative OAC (P = 0.038), with an
incrementally adverse effect on overall survival for stage I OAC with SOX2 loss
(HR 3.18, 1.18 to 8.56; P = 0.022). CONCLUSION: SOX2 is an independent prognostic
factor for long-term survival in OAC, especially in patients with stage I OAC.
PMID- 28692182
TI - GSK2878175, a pan-genotypic non-nucleoside NS5B polymerase inhibitor, in healthy
and treatment-naive chronic hepatitis C subjects.
AB - GSK2878175 is a potent, pan-genotypic, non-nucleoside, nonstructural protein 5B
palm polymerase inhibitor being developed for the treatment of chronic hepatitis
C (CHC). A first-in-human, randomized, placebo-controlled, dose escalation study,
evaluated the safety and pharmacokinetics of GSK2878175 administered as single
and repeat oral doses (once daily for 14 days) to healthy volunteers. A separate
proof-of-concept, placebo-controlled, repeat dose (once daily for 2 days) study
evaluated the safety, pharmacokinetics and antiviral activity of GSK2878175
monotherapy in treatment-naive, noncirrhotic, subjects with hepatitis C virus
(HCV) genotype 1 [1a and 1b], 2, or 3. No deaths or SAEs were reported in either
study, and treatment was well-tolerated. Across all the HCV genotypes, GSK2878175
monotherapy at doses of 10, 30 or 60 mg once daily for 2 days produced a
statistically significant multilog reduction (P<.001) in plasma HCV RNA log10
IU/mL from Baseline to 24, 48 and 72 hours after the first dose of GSK2878175
compared to placebo. The reduction in HCV RNA was sustained for a prolonged
period across all of the active treatment groups, consistent with the long
apparent half-life of GSK2878175 that was observed (mean t1/2 range: 60-63 hours
in the CHC subjects). In summary, GSK2878175, when administered to healthy
subjects and subjects with CHC, did not reveal any safety concerns that would
limit or preclude further clinical development. GSK2878175 monotherapy across a
wide dose range produced substantial reduction in HCV RNA, irrespective of HCV
genotype. The results from these studies support further evaluation of GSK2878175
based regimens.
PMID- 28692183
TI - Host range and distribution of small mammal fleas in South Africa, with a focus
on species of medical and veterinary importance.
AB - The host range and distribution of flea species on rodents and insectivores
across multiple vegetation types in South Africa were investigated. Habitat
suitability for flea species considered as important vectors of disease in humans
and domestic animals was modelled. Data originated from fleas that were recovered
from small mammals captured at 29 localities during 2009-2013 and published
literature searched for flea records. Climate-based predictor variables, widely
used in arthropod vector distribution, were selected and habitat suitability
modelled for 10 flea vector species. A total of 2469 flea individuals
representing 33 species and subspecies were collected from 1185 small mammals.
Ten of each of the flea and rodent species are plague vectors and reservoirs,
respectively. Multiple novel flea-host associations and locality records were
noted. Three vector species were recorded from insectivores. Geographic
distributions of flea species ranged from broad, across-biome distributions to
narrower distributions within one or two biomes. Habitat suitability models
performed excellently for the majority of flea vectors and identified regions of
summer and all-year rainfall as representing suitable habitats for most vector
species. Current knowledge of vector and disease ecology can benefit from similar
sampling approaches that will be important not only for South Africa, but also
for the sub-region.
PMID- 28692184
TI - Traditional empiric antibiotic treatment is still effective for neonatal fever.
PMID- 28692185
TI - Application of functional near infrared spectroscopy as supplementary examination
for diagnosis of clinical stages of psychosis spectrum.
AB - AIM: Research efforts aiming at neuroimaging-aided differential diagnosis for
psychiatric disorders have been progressing rapidly. A previous multisite study
has developed a supplementary diagnostic system using functional near-infrared
spectroscopy (fNIRS) that can be easily applied to clinical settings. However,
few neuroimaging biomarkers have been developed for the psychosis spectrum with
various clinical stages. METHODS: We employed the fNIRS as a clinical examination
device for 143 participants, comprising 47 ultra-high risk for psychosis (UHR)
individuals, 30 patients with first-episode psychosis (FEP), 34 patients with
chronic schizophrenia (ChSZ), and 33 healthy controls, who were independent of
the previous study. A 12-month follow-up measurement was also carried out on 34
UHR individuals (72%), 21 patients with FEP (70%), and 33 controls. The fNIRS
algorithm variables used for classification were the intensity and timing of
prefrontal activation following the start of the cognitive task as used in the
previous multisite study. RESULTS: The discrimination rate by timing of
activation was modest but it became acceptable after adjusting confounding
factors. Discrimination by intensity of activation was not improved by similar
adjustment. A total of 63.8%, 86.7%, and 81.3% patients were classified as UHR,
FEP, and ChSZ, respectively; and 85.1%, 86.7%, and 71.9% of patients in these
groups, respectively, were classified as being on the psychosis spectrum. In the
follow-up measurement, 88.2% of individuals with UHR and 95.0% of patients with
FEP were successfully classified into the psychosis spectrum group. CONCLUSION:
The fNIRS for supplementary clinical examination could be validly applied to
differentiating people with the psychosis spectrum in various clinical stages.
The fNIRS is a candidate biological marker for aiding diagnosis of psychosis
spectrum in routine clinical settings.
PMID- 28692186
TI - Access to specialist palliative care services by people with severe and
persistent mental illness: A retrospective cohort study.
AB - Compared to the general population, people with pre-existing serious and
persistent mental illness (SPMI) have higher rates of physical illness and die at
an earlier age, raising questions about their palliative and end-of-life care
needs when they are diagnosed with an incurable physical illness. In the present
study, we explored access to specialist palliative care services within one New
Zealand health district. Routinely-collected, de-identified patient information
on a cohort of people diagnosed with SPMI, and receiving specialist palliative
care services from the Capital and Coast District Health Board (CCDHB), was
compared to the general population from the same health district. People with
SPMI are 3.5 times less likely to receive specialist palliative services compared
to the general population from the Capital and Coast District Health Board. The
proportion of people identifying as Maori is 1.2 times higher in the SPMI cohort
than the general CCDHB population. The SPMI cohort experiences a higher level of
deprivation compared to the general population in the CCDHB. The present study
confirms that those diagnosed with an SPMI are less likely to use specialist
palliative care services at the end of life. Research using a national dataset is
needed to determine whether the study findings are applicable to the national
population.
PMID- 28692187
TI - Best Articles of 2016: A Reflection of Our Values.
PMID- 28692189
TI - Diversification of HP1-like Chromo Domain Proteins in Tetrahymena thermophila.
AB - Proteins that possess a chromo domain are well-known for their roles in
heterochromatin assembly and maintenance. The Heterochromatin Protein 1 (HP1)
family, with a chromo domain and carboxy-terminal chromo shadow domain, targets
heterochromatin through interaction with histone H3 methylated on lysine 9
(H3K9me2/3). The structural and functional diversity of these proteins observed
in both fission yeast and metazoans correlate with chromatin specialization. To
expand these studies, we examined chromo domain proteins in the ciliate
Tetrahymena thermophila, which has functionally diverse and developmentally
regulated heterochromatin domains. We identified thirteen proteins similar to
HP1. Together they possess only a fraction of the possible chromo domain subtypes
and most lack a recognizable chromo shadow domain. Using fluorescence microscopy
to track chromatin localization of tagged proteins through the life cycle, we
show evidence that in T. thermophila this family has diversified with biological
roles in RNAi-directed DNA elimination, germline genome structure, and somatic
heterochromatin. Those proteins with H3K27me3 binding sequence characteristics
localize to chromatin in mature nuclei, whereas those with H3K9me2/3 binding
characteristics localize to developing nuclei undergoing DNA elimination.
Findings point to an expanded and diversified family of chromo domain proteins
that parallels heterochromatin diversity in ciliates.
PMID- 28692190
TI - Dupuytren's contracture and handwork: A case-control study.
AB - OBJECTIVE: The objective of this study was to examine the association between
Dupuytren's contracture (DC), repetitive handwork (RHW), heavy handwork (HHW),
and/or vibration exposure. METHODS: Frequency and intensity of the three types of
handwork were collected and compared between DC patients and controls. Hours of
work were weighted by average "frequency," for RHW, and average "intensity," for
HHW and use of vibrating tool. Logistic regression was used to evaluate risk of
developing DC associated with the above-mentioned factors. RESULTS: Data from 129
cases (74 clinical, 106 controls) was analyzed. Family history, male gender and
age (decades) were associated with increased risk of DC. Results indicate that
the risk becomes substantial after about 30 years of steady RHW. Independent
effects of intensity-weighted HHW and vibrating exposure were not established.
CONCLUSIONS: Frequency-weighted RHW increases DC risk. Additionally, a strong
association between DC, male gender and heredity was found.
PMID- 28692191
TI - Capture and coding of industry and occupation measures: Findings from eight
National Program of Cancer Registries states.
AB - BACKGROUND: Although data on industry and occupation (I&O) are important for
understanding cancer risks, obtaining standardized data is challenging. This
study describes the capture of specific I&O text and the ability of a web-based
tool to translate text into standardized codes. METHODS: Data on 62 525 cancers
cases received from eight National Program of Cancer Registries (NPCR) states
were submitted to a web-based coding tool developed by the National Institute for
Occupational Safety and Health for translation into standardized I&O codes. We
determined the percentage of sufficiently analyzable codes generated by the tool.
RESULTS: Using the web-based coding tool on data obtained from chart abstraction,
the NPCR cancer registries achieved between 48% and 75% autocoding, but only 12
57% sufficiently analyzable codes. CONCLUSIONS: The ability to explore
associations between work-related exposures and cancer is limited by current
capture and coding of I&O data. Increased training of providers and registrars,
as well as software enhancements, will improve the utility of I&O data.
PMID- 28692192
TI - Aromatic hydrocarbons and risk of skin cancer by anatomical site in 25 000 male
offshore petroleum workers.
AB - BACKGROUND: We prospectively examined skin cancer risk according to occupational
exposure to aromatic hydrocarbons with adjustment for ultraviolet radiation
exposure, in a cohort of 24 917 male offshore petroleum workers. METHODS: Hazard
ratios (HRs) and 95% confidence intervals were estimated with Cox regression
adapted to a stratified case-cohort design. RESULTS: During 13.5 years of follow
up, 112 cutaneous melanomas (CMs) and 70 non-melanoma skin cancers were
identified. Increased risks of CM and of squamous cell carcinoma on the forearm
and hand were seen among those ever exposed to crude oil or benzene. For skin
cancers of the forearm and hand combined, cumulative and duration metrics of
benzene exposure showed Ptrends of 0.031 and 0.003, respectively. CONCLUSIONS:
Our results support an association between exposure to crude oil or benzene and
skin cancer risk on hands and forearms among offshore petroleum workers. Dermal
uptake of polycyclic aromatic hydrocarbons or benzene may explain this
association.
PMID- 28692193
TI - Predictors of transitions from single to multiple job holding: Results of a
longitudinal study among employees aged 45-64 in the Netherlands.
AB - OBJECTIVES: To construct prediction models for transitions to combination
multiple job holding (MJH) (multiple jobs as an employee) and hybrid MJH (being
an employee and self-employed), among employees aged 45-64. METHODS: A total of
5187 employees in the Netherlands completed online questionnaires annually
between 2010 and 2013. We applied logistic regression analyses with a backward
elimination strategy to construct prediction models. RESULTS: Transitions to
combination MJH and hybrid MJH were best predicted by a combination of factors
including: demographics, health and mastery, work characteristics, work history,
skills and knowledge, social factors, and financial factors. Not having a
permanent contract and a poor household financial situation predicted both
transitions. Some predictors only predicted combination MJH, e.g., working part
time, or hybrid MJH, e.g., work-home interference. CONCLUSIONS: A wide variety of
factors predict combination MJH and/or hybrid MJH. The prediction model approach
allowed for the identification of predictors that have not been previously
studied.
PMID- 28692194
TI - Trends in exposure to respirable crystalline silica (1986-2014) in Australian
mining.
AB - BACKGROUND: Respirable crystalline silica (RCS) has been associated with severe
health risks. Exposures in Western Australia (WA) have been typically high in
hard-rock mining and have reduced substantially since the mid-1900s. We described
trends in RCS exposure in WA miners over the past 30 years. METHODS: A total of
79 445 reported personal RCS exposure measurements, covering the years 1986-2014,
were examined. Mixed-effects models were applied to estimate RCS exposure levels,
including spline terms to estimate a time trend. RESULTS: An overall downward
trend of about -8% per year was observed for RCS exposures in WA mining. Highest
RCS exposure levels were modeled for base metal mining and exploration settings.
Drilling occupations were among the highest exposed jobs. CONCLUSION: RCS
exposure levels have fallen considerably in the last three decades. However,
there are still mining occupations that may need further attention to avoid
adverse health effects in these workers.
PMID- 28692195
TI - Homologous Catalysts Based on Fe-Doped CoP Nanoarrays for High-Performance Full
Water Splitting under Benign Conditions.
AB - The design and development of earth-abundant electrocatalysts for efficient full
water splitting under mild conditions are highly desired, yet remain a
challenging task. A homologous Fe-doped Co-based nanoarray incorporating
complementary catalysts is shown to effect high-performance and durable water
splitting in near-neutral media. Iron-doped cobalt phosphate borate nanoarray on
carbon cloth (Fe-Co-Pi-Bi/CC) derived from iron-doped cobalt phosphide on CC (Fe
CoP/CC) through oxidative polarization behaves as a highly active bimetallic
electrocatalyst for water oxidation with an overpotential of 382 mV to afford a
catalytic current density of 10 mA cm-2 in 0.1 m potassium borate (K-Bi, pH 9.2).
Fe-CoP/CC is also highly active for the hydrogen evolution reaction, capable of
driving 10 mA cm-2 at an overpotential of only 175 mV in 0.1 m K-Bi. A two
electrode water electrolyzer incorporating Fe-Co-Pi-Bi/CC as anode and Fe-CoP/CC
as cathode achieves 10 mA cm-2 water-splitting current at a cell voltage of 1.95
V with strong long-term electrochemical durability.
PMID- 28692196
TI - Genotype-phenotype study in patients with valosin-containing protein mutations
associated with multisystem proteinopathy.
AB - Mutations in valosin-containing protein (VCP), an ATPase involved in protein
degradation and autophagy, cause VCP disease, a progressive autosomal dominant
adult onset multisystem proteinopathy. The goal of this study is to examine if
phenotypic differences in this disorder could be explained by the specific gene
mutations. We therefore studied 231 individuals (118 males and 113 females) from
36 families carrying 15 different VCP mutations. We analyzed the correlation
between the different mutations and prevalence, age of onset and severity of
myopathy, Paget's disease of bone (PDB), and frontotemporal dementia (FTD), and
other comorbidities. Myopathy, PDB and FTD was present in 90%, 42% and 30% of the
patients, respectively, beginning at an average age of 43, 41, and 56 years,
respectively. Approximately 9% of patients with VCP mutations had an amyotrophic
lateral sclerosis (ALS) phenotype, 4% had been diagnosed with Parkinson's disease
(PD), and 2% had been diagnosed with Alzheimer's disease (AD). Large
interfamilial and intrafamilial variation made establishing correlations
difficult. We did not find a correlation between the mutation type and the
incidence of any of the clinical features associated with VCP disease, except for
the absence of PDB with the R159C mutation in our cohort and R159C having a later
age of onset of myopathy compared with other molecular subtypes.
PMID- 28692197
TI - The Asia-Pacific Working Party on Non-alcoholic Fatty Liver Disease guidelines
2017-Part 2: Management and special groups.
PMID- 28692198
TI - Longitudinal community walking activity in Duchenne muscular dystrophy.
AB - INTRODUCTION: Natural history studies for Duchenne muscular dystrophy (DMD) have
not included measures of community ambulation. METHODS: Step activity (SA)
monitors quantified community ambulation in 42 boys (ages 4-16 years) with DMD
with serial enrollment up to 5 years by using a repeated-measures mixed model.
Additionally, data were compared with 10-meter walk/run (10mWR) speed to
determine validity and sensitivity. RESULTS: There were significant declines in
average strides/day and percent strides at moderate, high and pediatric high
rates as a function of age (P < 0.05). Significant correlations for 10mWR versus
high and low stride rates were found at baseline (P < 0.05). SA outcomes were
sensitive to change over 1 year, but the direction and parameter differed by age
group (younger vs. older). Changes in strides/day and percentages of high
frequency and low frequency strides correlated significantly with changes in
10mWR speed (P < 0.05). DISCUSSION: Community ambulation data provide valid and
sensitive real-world measures that may inform clinical trials. Muscle Nerve 57:
401-406, 2018.
PMID- 28692199
TI - We need to change how we deal with continuous pain in neonates.
PMID- 28692200
TI - Cardiorespiratory physiology in early infancy.
PMID- 28692202
TI - The role of networks in improving perinatal and neonatal care.
PMID- 28692203
TI - More voice, less noise in NICUs.
PMID- 28692204
TI - The new generation super-mini percutaneous nephrolithotomy (SMP) system: a step
by-step guide.
AB - OBJECTIVE: To present our novel miniaturised endoscopic system and describe a
step-by-step guide for successful implementation of the super-mini percutaneous
nephrolithotomy (SMP). PATIENTS AND METHODS: The new-generation SMP endoscopic
system consists of (i) a 40 000-pixel super-mini nephroscope with an 8.0-F outer
diameter and 7.5-F inner diameter dismountable sheath, and (ii) a newly designed
irrigation-suction sheath available in either 12 F or 14 F. The irrigation
suction sheath is a two-layered metal structure. The key feature of the
irrigation-suction sheath is to allow irrigation and suction respectively (the
inflow through the space between the two layers of the sheath, the outflow
through the central lumen of the sheath). This property improves irrigation and
stone clearance despite reduced instrument dimension. In all, 59 patients with
renal stones underwent new-generation SMP between April 2016 and December 2016.
The percutaneous tract dilatation was carried out to 14 F. Lithotripsy was
performed using either holmium laser or a pneumatic lithotripter. Stone fragments
were sucked out by vacuum suctioning through the sheath. A nephrostomy tube or JJ
stent was placed only if clinically indicated. Low-dose computed tomography was
performed to assess the stone-free status on the morning after the procedure.
RESULTS: The mean stone burden was 2.4 cm. Of the 59 patients, nine had diabetes
and five had hypertension. SMP was completed successfully in all patients with a
mean operation duration of 32.9 min and a mean haemoglobin decrease of 13 g/L.
The stone-free rate was 91.5%. Complications occurred in 5.1% of the patients,
all of them were Clavien-Dindo Grade I (minor fever managed by antipyretic
therapy), and no transfusions were needed. CONCLUSION: The new-generation SMP
system is safe, feasible, and effective for managing renal calculi of <3 cm, with
the advantages of a small percutaneous tract, less blood loss, high efficacy in
stone clearance, improved visual field, short operation duration, and ease of
operating.
PMID- 28692205
TI - Limitations in the inverse association between psychological resilience and
depression in prostate cancer patients experiencing chronic physiological stress.
AB - OBJECTIVE: To investigate the effect of chronic stress as measured in cortisol
concentrations upon the association between psychological resilience (PR) and
depression in prostate cancer (PCa) patients. METHODS: A total of 104 men with
PCa completed inventories on PR, depression, and background factors, plus gave a
sample of their saliva for cortisol assay. RESULTS: The inverse correlation
between PR and depression was present only for PCa patients with low or moderate
concentrations of salivary cortisol (when classified as more than 1.0 SD below
the mean vs within 1.0 SD of the group mean) but not for those men whose cortisol
was >1.0 SD from the group mean. Specific PR factors and behaviours that made the
greatest contribution to depression were identified for the low and moderate
cortisol groups. CONCLUSIONS: These results suggest that there are particular
aspects of PR that are most strongly related to depression, but that PR's inverse
association with depression may be absent in participants with extreme chronic
physiological stress.
PMID- 28692206
TI - Crystalline Neutral Allenic Diborene.
AB - A zwitterionic boraalkenyl boronium 3 was synthesized by reduction of cyclic
(alkyl)(amino)carbene (cAAC) and trimethylphosphine (PMe3 )-coordinated
tetrabromodiborane 2 with KC8 in the presence of PMe3 . Further reduction of 3
led to the formation of neutral allenic diborene 4. X-ray diffraction and
computational studies revealed that 4 features the cumulated C=B and B=B double
bonds. The reaction of 4 with four isonitrile molecules afforded a heterocycle 5
with the B2 C3 five-membered ring, via a complete scission of the B=B bond of 4.
PMID- 28692207
TI - Comment on: "Hemocompatibility of Superhemophobic Titania Surfaces".
PMID- 28692208
TI - HCV antigen instead of RNA testing to diagnose acute HCV in patients treated in
the Dutch Acute HCV in HIV Study.
AB - INTRODUCTION: Affordable and sensitive screening methods for acute hepatitis C
(HCV) are necessary to successfully intervene in the current HCV epidemic among
HIV-positive men having sex with men. HCV core antigen (Ag) testing has been
proven effective in diagnosing chronic HCV-infected patients at low costs. We
studied the characteristics of HCV Ag testing in acute HCV-infected HIV-positive
patients. Methods Plasma samples were selected from acutely HCV genotype 1
infected patients treated with peginterferon, ribavirin and boceprevir in the
Dutch Acute HCV in HIV Study. The control group consisted of HIV-positive
patients with a newly raised alanine aminotransferase (ALT) (>41 U/L) in whom HCV
RNA was undetectable and who were tested for HCV Ag. Spearman correlation
coefficient between HCV RNA and HCV Ag was calculated together with the
sensitivity and specificity of HCV Ag testing at acute HCV diagnosis. RESULTS AND
DISCUSSION: Upon acute HCV diagnosis, HCV Ag was identified in 39 out of 44
patients with detectable HCV RNA levels. In all 23 control patients without
detectable HCV RNA in plasma, HCV Ag was undetectable as well. This resulted in a
sensitivity and specificity of HCV Ag of respectively 89% (95% CI 75-96) and 100%
(95% CI 82-100). The correlation between HCV Ag and HCV RNA was 0.97 (p < 0.001)
upon diagnosis. CONCLUSION: The data presented in this study suggest that HCV Ag
testing is a sensitive and specific method that can be used in diagnosing AHCV in
HIV-infected patients.
PMID- 28692209
TI - The science of Durban, AIDS 2016.
AB - INTRODUCTION: The science presented at the 21st International AIDS Conference in
Durban, South Africa, in July 2016, addressed the state of the field across
basic, clinical, prevention, law and policy and implementation science. METHODS
AND RESULTS: The AIDS response has seen remarkable achievements in scientific
advances, in translation of those advances into prevention, treatment and care
for affected individuals and communities, and in large scale implementation -
reaching 18 million people with antiviral therapy by mid-year 2016. Yet incident
HIV infections in adults remain stubbornly stable and are increasing in some
regions and among adolescents and adults in some key populations, challenging
current science, policy and programming. There have been important advances in
both preventive vaccines and in cure research, but both areas require ongoing
investment and innovation. Clinical research has flourished with new agents,
regimens, delivery modes and diagnostics but has been challenged by aging and
increasingly complex patient populations, long-term adherence challenges, co
infections and co-morbidities, and unresolved issues in TB management and
epidemic control. It is an extraordinary period of innovation in prevention, yet
the promise of new tools and combination approaches have yet to deliver epidemic
HIV control. CONCLUSIONS: Proven interventions, most notably pre-exposure
prophylaxis, PrEP, have been limited in rollout and impact. Treatment as
prevention has the promise to improve clinical outcomes but remains uncertain as
a prevention tool to reduce population-level HIV incidence. The improvement of
legal, policy and human rights environments for those most at risk for HIV
acquisition and most at risk for lack of access to essential services; sexual and
gender minorities, sex workers of all genders, people who inject drugs, and
prisoners and detainees remain among the greatest unmet needs in HIV/AIDS.
Failure to do better for these individuals and communities could undermine the
HIV response.
PMID- 28692210
TI - Agency as a mediator in the pathway from transactional sex to HIV among pregnant
women in Swaziland: a multigroup path analysis.
AB - INTRODUCTION: Transactional sex is a structural driver of HIV for women and girls
in sub-Saharan Africa. In transactional relationships, sexual and economic
obligations intertwine and may have positive and negative effects on women's
financial standing and social status. We conducted a clinic-based survey with
pregnant women in Swaziland using a locally validated transactional sex scale to
measure the association between subjective social status, transactional sex, and
HIV status, and to assess whether this association differed according to a
woman's agency within her relationship. METHODS: We recruited a convenience
sample of 406 pregnant women at one rural and one urban public antenatal clinic
in Swaziland and administered a behavioural survey that was linked to participant
HIV status using clinic records. We then conducted a multigroup path analysis to
test three hypotheses: (1) that more engagement in transactional sex is
associated with decreased condom use and increased subjective social status; (2)
that subjective social status mediates the relationship between transactional sex
and HIV status; and (3) that these relationships are different across groups
according to whether or not a woman reported any indicator of constrained agency
within her relationship. RESULTS: The amount and value of material goods received
from a sexual partner was significantly and positively associated with higher
subjective social status among all participants. As the amount of material goods
received from a partner increased, women who reported no indicators of
constrained agency were less likely to use condoms. Conversely, there was no
relationship between transactional sex and condom use among women who reported
any indicator of constrained relationship agency. Among women who reported any
indicator of constrained agency, HIV was significantly associated with lower
subjective social status. CONCLUSIONS: Relationship agency likely plays a key
role in determining which mechanisms create HIV risk for women in transactional
relationships. Interventions to mitigate these risks must address social forces
that penalize women who engage in sexual relationships as well as structural
drivers of gendered economic disparity that reduce women's agency within their
sexual and romantic relationships.
PMID- 28692212
TI - ?
PMID- 28692211
TI - Integrating HIV and substance use services: a systematic review.
AB - INTRODUCTION: Substance use is an important risk factor for HIV, with both
concentrated in certain vulnerable and marginalized populations. Although their
management differs, there may be opportunities to integrate services for
substance use and HIV. In this paper we systematically review evidence from
studies that sought to integrate care for people living with HIV and substance
use problems. METHODS: Studies were included if they evaluated service
integration for substance use and HIV. We searched multiple databases from
inception until October 2015. Articles were screened independently by two
reviewers and assessed for risk of bias. RESULTS AND DISCUSSION: 11,057 records
were identified, with 7616 after removal of duplicates. After screening titles
and abstracts, 51 met the inclusion criteria. Integration models were categorized
by location (HIV, substance use and other facilities), level of integration from
mirco (integrated care delivered to individuals) to macro (system level
integrations) and degree of integration from least (screening and counselling
only) to most (care for HIV, substance use and/or other illnesses at the same
facility). Most reported descriptive or cohort studies; in four randomized
control trials integrated activities improved patient outcomes. There is
potential for integrating services at all facility types, including mobile health
services. While services offering screening only can achieve synergies, there are
benefits from delivering integrated treatment for HIV and substance use,
including ease of referral to other mental health and social services.
CONCLUSIONS: Our review used a wide range of databases and conference archives to
increase representation of papers from low- and middle-income countries.
Limitations include the overrepresentation of studies from the United States, and
the descriptive nature of the majority of papers. The evidence reviewed shows
that greater integration offers important benefits in both patient and service
outcomes but further research and outcome reporting is needed to better
understand innovative and holistic care models at the complex intersection of
substance use and HIV services.
PMID- 28692213
TI - [Fever : to treat or not to treat ?]
AB - Fever is routinely faced during medical practice. Although it is part of the
immune response against pathogens, it is often seen as deleterious and a source
of discomfort leading to the use of antipyretic drugs. However, few clinical data
support this common practice. On the contrary, to date, results tilt in favor of
the beneficial effect of fever, such as a better immune response and inhibition
of pathogen growth. Data encourage the treatment of fever only in certain
conditions such as neurological symptoms, cardio-pulmonary failure, or fever of
non-infectious origin. In fact recent evidence stress that systematic treatment
of fever do not improve, but nor deteriorate, the disease outcome. This suggests
to only treat the poorly tolerated fevers.
PMID- 28692214
TI - [Iron deficiency : a new target in treating chronic heart failure ?]
AB - Iron deficiency is now recognized as an independent predictor of poor outcome in
patients with chronic heart failure and reduced left ventricular ejection
fraction. In randomized controlled trials, treatment with ferric carboxymaltose
results in improvement in functional capacity, symptoms and quality of life, and
might reduce hospitalizations. Thus, the recent European Society of Cardiology
guidelines on heart failure recommend treating these patients with intravenous
ferric carboxymaltose, whether or not anemic.
PMID- 28692215
TI - [Faecal calprotectin : a useful tool for the primary care physician ?]
AB - Faecal calprotectin (FC) is a marker of intestinal inflammation. FC dosing has a
sensitivity between 80-100% for differentiating functional and organic intestinal
disease. It is therefore a very useful diagnostic tool in general practice, where
the prevalence of functional disease is particularly high. Nevertheless, FC is
not specific for inflammatory bowel diseases and cannot distinguish between
various inflammatory conditions. FC cut-off values are not clearly defined.
Nevertheless, levels < 150 ug/g are considered ruling out organic disease and
levels > 150 ug/g warrant an endoscopy. In the intermediate range 50-150 ug/g,
the result is indeterminate and the decision to perform further tests should be
made on an individual basis.
PMID- 28692216
TI - [Digoxin and atrial fibrillation in 2016].
AB - Various properties of digoxin have been exploited for decades, amongst which are
its positive inotropy used in the treatment of heart failure, and its vagotonic
effect used to slow ventricular response to atrial fibrillation. Pharmacologic
properties of digoxin are however characterised by a narrow therapeutic interval,
and recent observational studies suggest a potential association with increased
mortality in patients with atrial fibrillation. As a result and because of
available alternative therapeutic strategies, current guidelines do not recommend
digoxin as first line treatment of atrial fibrillation. Digoxin may be considered
in patients with heart failure and atrial fibrillation with rapid ventricular
response when other therapeutic options cannot be pursued.
PMID- 28692217
TI - [Magnesium in daily practice].
AB - The magnesium is the 4th cation in the human body behind sodium, potassium and
calcium. It is often referred to as the forgotten cation of modern medicine
because of a lack of knowledge about its physiology and its potential medical
use. Recent medical literature has shown renewed interest for the magnesium with
publications about its role in diversified fields from prevention of muscular
cramps, cardiovascular risk factors prevention trough to neuroprotection in
stroke. However, we cannot recommend the use of magnesium in adults in our
clinical practice, beyond the simple correction of hypomagnesemia, pre-eclampsia
and possibly the treatment of torsades de pointes.
PMID- 28692218
TI - [Interpretation of high-sensitivity troponin in patients with chronic kidney
failure].
AB - New assays with lower levels of detection of troponin (" high-sensitivity
troponin ") increase the difficulty of interpretation of this test for the
diagnosis of acute coronary syndrome in patients with chronic kidney disease
(CKD). Their baseline concentration of troponin is frequently above the upper
reference level, which lowers its specificity. To improve its diagnostic
performance after clinical and electrocardiographic evaluation, cut-off levels 2
to 3 times higher than the standard reference have been suggested. Serial
measurements can also add diagnostic value. In patients without acute coronary
syndrome including patients with CKD, chronic elevation of troponin is a
predictive factor of mortality. Its standardized measurement in clinical practice
is still being investigated.
PMID- 28692219
TI - ?
PMID- 28692220
TI - ?
PMID- 28692221
TI - ?
PMID- 28692222
TI - ?
PMID- 28692223
TI - ?
PMID- 28692224
TI - ?
PMID- 28692225
TI - ?
PMID- 28692226
TI - ?
PMID- 28692227
TI - ?
PMID- 28692228
TI - [Zika virus : a review].
AB - Since early 2015, the Zika virus epidemic has spread rapidly through South
America and the Caribbean and the first cases of local transmission have just
been reported in Florida. Maternal infection during pregnancy can cause serious
birth defects. Pregnant women and their partners should avoid travelling to areas
of Zika epidemic.
PMID- 28692229
TI - [Zika virus : from research to vaccine].
AB - Zika virus has recently emerged as new teratogenic agent. Research is drastically
increasing to allow a better comprehension of the role of this emerging virus in
the induction of fetal cerebral anomalies. Several epidemiological and
microbiological aspects may explain a higher virulence of the current strain.
Various animal models have been developed and confirm the materno-fetal
transmission as well as the induction of cerebral development's disorders. In
parallel, various companies are working to develop a vaccine and antiviral
medicine against Zika virus. Despite promising results, the road remains long
until a vaccine or antiviral medicines are available.
PMID- 28692230
TI - [Virtual reality simulation training in gynecology: review and perspectives].
AB - Laparoscopic simulation has rapidly become an important tool for learning and
acquiring technical skills in surgery. It is based on two different complementary
pedagogic tools : the box model trainer and the virtual reality simulator. The
virtual reality simulator has shown its efficiency by improving surgical skills,
decreasing operating time, improving economy of movements and improving self
confidence. The main objective of this tool is the opportunity to easily organize
a regular, structured and uniformed training program enabling an automated
individualized feedback.
PMID- 28692231
TI - [The menopausal hormone therapy in 2016].
AB - The menopausal hormone therapy (MHT) is the first line treatment for climacteric
symptoms related to estrogen deficiency. A personalized evaluation of the benefit
risk ratio should precede a MHT prescription, and take into consideration
cardiovascular, thromboembolic, oncological and osteoporosis risks. MHT should be
prescribed at the lowest effective dose and for the shortest duration, respecting
the window of opportunity in the 10 years following menopause or before the age
of 60 years. The choice of the MHT type depends on the patient's profile, her
medical history and personal preferences, with the aim of improving quality of
life from a physical, psychological and sexual point of view.
PMID- 28692232
TI - [Osteoporosis in menopausal women between 40 and 65 years old : an algorithm for
the gynaecologist].
AB - Osteoporosis is a bone disease that promotes the development of fragility
fractures. An algorithm is proposed for the gynaecologists'use to diagnose and
treat osteoporosis in young menopausal women. The fracture risk can be calculated
with the FRAX tool. If the 10-year fracture risk is >= 10 %, a bone densitometry
is recommended, and the result is integrated in the FRAX tool. If the risk is
between 10 and 20 %, a treatment should be discussed individually and, in some
cases, a pharmacologic preventive treatment, by menopause hormonal treatment or
SERMs, can be initiated. A pharmacologic treatment (bisphosphonates or denosumab)
is recommended in case of previous fragility fracture or risk >= 20 %,
independently of a T-score < -2.5 DS. Patients have to be referred in case of
treatment failure or intolerance, and at the end of any denosumab therapy.
PMID- 28692233
TI - [Sleep apnea in pregnancy].
AB - Snoring, chronic rhinitis and fragmentation of sleep are common symptoms in
pregnancy, especially in the third trimester. The prevalence of obstructive sleep
apnea is also increased in pregnant women and can be associated with pregnancy
induced hypertension, preeclampsia and diabetes mellitus. The fetus is as well
exposed to a higher risk of prematurity and intra-uterine growth restriction.
Given the lack of adequate screening tool, the diagnosis of obstructive sleep
apnea is a challenge for the physician and a high degree of clinical suspicion is
necessary in order to identify the patients at risk and propose an appropriate
management.
PMID- 28692234
TI - ?
PMID- 28692235
TI - ?
PMID- 28692236
TI - ?
PMID- 28692237
TI - ?
PMID- 28692238
TI - ?
PMID- 28692239
TI - ?
PMID- 28692240
TI - ?
PMID- 28692242
TI - Hybridization of Metal Nanoparticles with Metal-Organic Frameworks Using Protein
as Amphiphilic Stabilizer.
AB - Here, a facile strategy is reported to efficiently hybridize metal nanoparticles
(MNPs) with typical metal-organic frameworks (MOFs) of ZIF-8 (zeolitic
imidazolate framework-8), which employs bovine serum albumin (BSA, a serum
albumin protein derived from cows) as the amphiphilic stabilizer to increase the
affinity of MNP toward MOFs. For instance, the as-synthesized PdNPs/ZIF-8
composites with diameter from 100 to 200 nm always maintain well-defined
crystalline structure, and the PdNPs with small size of ~2 nm are well-dispersed
in the crystal of MOFs without serious aggregations due to the BSA stabilizer. In
Suzuki cross-coupling reactions of aryl halide, the PdNPs/ZIF-8 as catalysts have
exhibited high activity and satisfied reusability owing to the use of BSA
stabilizer as well as the fixing of MOFs matrixes. In addition, the strategy also
can be extended to synthesize other kinds of MNPs/MOFs hybrid composites with
tunable particle size, which brings more opportunity for functional MOFs hybrid
materials.
PMID- 28692243
TI - Biosynthesis of Astrocytic Trehalose Regulates Neuronal Arborization in
Hippocampal Neurons.
AB - Trehalose is a nonreducing disaccharide that has recently attracted much
attention because of its ability to inhibit protein aggregation, induce
autophagy, and protect against dissections and strokes. In vertebrates, the
biosynthesis of trehalose was long considered absent due to the lack of annotated
genes involved in this process. In contrast, trehalase (TreH), which is an enzyme
required for the cleavage of trehalose, is known to be conserved and expressed.
Here, we show that trehalose is present as an endogenous metabolite in the rodent
hippocampus. We found that primary astrocytes were able to synthesize trehalose
and release it into the extracellular space. Notably, the TreH enzyme was
observed only in the soma of neurons, which are the exclusive users of this
substrate. A statistical analysis of the metabolome during different stages of
maturation indicated that this metabolite is implicated in neuronal maturation. A
morphological analysis of primary neurons confirmed that trehalose is required
for neuronal arborization.
PMID- 28692244
TI - Selenylsulfide Bond-Launched Reduction-Responsive Superparamagnetic Nanogel
Combined of Acid-Responsiveness for Achievement of Efficient Therapy with Low
Side Effect.
AB - With the objective to achieve in-between reduction-responsive drug release,
selenylsulfide bond was first explored as a reduction cleavable linkage, compared
with the most commonly employed disulfide and diselenide bonds. The reductive
nanogel, with a combination of superparamagnetic and acid responsiveness, was
fabricated. The expected release profiles were testified. Cytotoxicity assays
illustrated the remarkable inhibition to the growth of HeLa cells, in contrast,
high tolerance to L02 cells. In vivo investigation exhibited the obvious
shrinkage in tumor but a healthy appearance. Hematoxylin-eosin staining and
histological examination revealed the lower toxicity. The complex nanogels would
have appeared highly promising in cancer therapy.
PMID- 28692245
TI - Insight into a New Binding Site of Zinc Ions in Fibrillar Amylin.
AB - Amylin peptides are secreted together with insulin and zinc ions from pancreatic
beta-cells. Under unknown conditions, the amylin peptides aggregate to produce
oligomers and fibrils, and in some cases Zn2+ ions can bind to amylin peptides to
form Zn2+-aggregate complexes. Consequently, these aggregates lead to the death
of the beta-cells and a decrease in insulin, which is one of the symptoms of type
2 diabetes (T2D). Therefore, it is crucial to investigate the binding sites of
the Zn2+ ions in fibrillary amylin. It was previously found by in vitro and
simulation studies that Zn2+ ion binds to two or four His residues in the turn
domain of fibrillary amylin. In the current study, we present a new Zn2+ binding
site in the N-terminus of fibrillary amylin with three different coordination
modes. Our simulations showed that Zn2+ ions bind to polymorphic amylin fibrils
with a preference to bind to four Cys residues rather than two Cys residues of
two neighboring amylin monomers. The new binding site leads to conformational
changes, increases the number of polymorphic states, and demonstrates the
existence of competition between various binding sites. Our study provides
insight into the molecular mechanisms through which Zn2+ ions that play a
critical role in amylin aggregation can bind to amylin and promote amylin
aggregation in T2D.
PMID- 28692246
TI - Discovery of S...C=N Intramolecular Bonding in a Thiophenylcyanoacrylate-Based
Dye: Realizing Charge Transfer Pathways and Dye...TiO2 Anchoring Characteristics
for Dye-Sensitized Solar Cells.
AB - Donor-pi-acceptor dyes containing thiophenyl pi-conjugated units and
cyanoacrylate acceptor groups are among the best-performing organic chromophores
used in dye-sensitized solar cell (DSC) applications. Yet, the molecular origins
of their high photovoltaic output have remained unclear until now. This
synchrotron-based X-ray diffraction study elucidates these origins for the high
performance thiophenylcyanoacrylate-based dye MK-2 (7.7% DSC device efficiency)
and its molecular building block, MK-44. The crystal structures of MK-2 and MK-44
are both determined, while a high-resolution charge-density mapping of the
smaller molecule was also possible, enabling the nature of its bonding to be
detailed. A strong S...C=N intramolecular interaction is discovered, which bears
a bond critical point, thus proving that this interaction should be formally
classified as a chemical bond. A topological analysis of the pi-conjugated
portion of MK-44 shows that this S...C=N bonding underpins the highly efficient
intramolecular charge transfer (ICT) in thiophenylcyanoacrylate dyes. This
manifests as two bipartite ICT pathways bearing carboxylate and nitrile end
points. In turn, these pathways dictate a preferred COO/CN anchoring mode for the
dye as it adsorbs onto TiO2 surfaces, to form the dye...TiO2 interface that
constitutes the DSC working electrode. These results corroborate a recent
proposal that all cyanoacrylate groups anchor onto TiO2 in this COO/CN binding
configuration. Conformational analysis of the MK-44 and MK-2 crystal structures
reveals that this S...C=N bonding will persist in MK-2. Accordingly, this newly
discovered bond affords a rational explanation for the attractive photovoltaic
properties of MK-2. More generally, this study provides the first unequivocal
evidence for an S...C=N interaction, confirming previous speculative assignments
of such interactions in other compounds.
PMID- 28692248
TI - One-Step Fabrication of Fe(OH)3@Cellulose Hollow Nanofibers with Superior
Capability for Water Purification.
AB - The conventional strategies employed for the synthesis of hollow nanofibers
(HNFs) require either multistep treatments or special design of the equipment. An
additional annealing process is always required, which inevitably consumes more
energy and raises the manufacturing cost. In addition, the annealing process may
also cause a waste of the matrix materials and the release of toxic gases.
Herein, we report for the first time a novel one-step synthesis of hollow hybrid
nanofibers via electrospinning. Cellulose was chosen as the polymer matrix, and
Fe(OH)3 nanoparticles were grown in situ on the nanofibers during
electrospinning. There was no need to remove cellulose to create the hollow
nanofiber structure. This can significantly simplify the fabrication process
without any negative influence to the air. The obtained Fe(OH)3@cellulose HNF
membranes exhibited great mechanical properties and an extremely high water flux
of 11 200 L m-2 h-1 bar-1. They could effectively remove various pollutants in
water, including phosphate, heavy metal ions, and organic dyes, with excellent
reusability. Importantly, this approach could also be applied for the fabrication
of other hybrid HNFs, which may serve in a broad range of scientific and
engineering applications, including water purification, energy conversion and
storage, catalysts, sensors, and so on.
PMID- 28692247
TI - Site-Specific Phosphorylation of PSD-95 PDZ Domains Reveals Fine-Tuned Regulation
of Protein-Protein Interactions.
AB - The postsynaptic density protein of 95 kDa (PSD-95) is a key scaffolding protein
that controls signaling at synapses in the brain through interactions of its PDZ
domains with the C-termini of receptors, ion channels, and enzymes. PSD-95 is
highly regulated by phosphorylation. To explore the effect of phosphorylation on
PSD-95, we used semisynthetic strategies to introduce phosphorylated amino acids
at four positions within the PDZ domains and examined the effects on interactions
with a large set of binding partners. We observed complex effects on affinity.
Most notably, phosphorylation at Y397 induced a significant increase in affinity
for stargazin, as confirmed by NMR and single molecule FRET. Additionally, we
compared the effects of phosphorylation to phosphomimetic mutations, which
revealed that phosphomimetics are ineffective substitutes for tyrosine
phosphorylation. Our strategy to generate site-specifically phosphorylated PDZ
domains provides a detailed understanding of the role of phosphorylation in the
regulation of PSD-95 interactions.
PMID- 28692249
TI - The Emergence of Phenolic Glycans as Virulence Factors in Mycobacterium
tuberculosis.
AB - Tuberculosis is the leading infectious cause of mortality worldwide. The global
epidemic, caused by Mycobacterium tuberculosis, has prompted renewed interest in
the development of novel vaccines for disease prevention and control. The cell
envelope of M. tuberculosis is decorated with an assortment of glycan structures,
including glycolipids, that are involved in disease pathogenesis. Phenolic
glycolipids and the structurally related para-hydroxybenzoic acid derivatives
display potent immunomodulatory activities and have particular relevance for both
understanding the interaction of the bacterium with the host immune system and
also in the design of new vaccine and therapeutic candidates. Interest in
glycobiology has grown exponentially over the past decade, with advancements
paving the way for effective carbohydrate based vaccines. This review highlights
recent advances in our understanding of phenolic glycans, including their
biosynthesis and role as virulence factors in M. tuberculosis. Recent chemical
synthesis approaches and biochemical analysis of synthetic glycans and their
conjugates have led to fundamental insights into their roles in host-pathogen
interactions. The applications of these synthetic glycans as potential vaccine
candidates are discussed.
PMID- 28692250
TI - Silicene Flowers: A Dual Stabilized Silicon Building Block for High-Performance
Lithium Battery Anodes.
AB - Nanostructuring is a transformative way to improve the structure stability of
high capacity silicon for lithium batteries. Yet, the interface instability issue
remains and even propagates in the existing nanostructured silicon building
blocks. Here we demonstrate an intrinsically dual stabilized silicon building
block, namely silicene flowers, to simultaneously address the structure and
interface stability issues. These original Si building blocks as lithium battery
anodes exhibit extraordinary combined performance including high gravimetric
capacity (2000 mAh g-1 at 800 mA g-1), high volumetric capacity (1799 mAh cm-3),
remarkable rate capability (950 mAh g-1 at 8 A g-1), and excellent cycling
stability (1100 mA h g-1 at 2000 mA g-1 over 600 cycles). Paired with a
conventional cathode, the fabricated full cells deliver extraordinarily high
specific energy and energy density (543 Wh kgca-1 and 1257 Wh Lca-1,
respectively) based on the cathode and anode, which are 152% and 239% of their
commercial counterparts using graphite anodes. Coupled with a simple, cost
effective, scalable synthesis approach, this silicon building block offers a
horizon for the development of high-performance batteries.
PMID- 28692251
TI - Reduced Graphene Oxide-Reinforced Polymeric Films with Excellent Mechanical
Robustness and Rapid and Highly Efficient Healing Properties.
AB - The fabrication of nanofiller-reinforced intrinsic healable polymer composite
films with both excellent mechanical robustness and highly efficient healability
is challenging because the mobility of the polymer chains is suppressed by the
incorporated nanofillers. In this study, we exploit the reversible host-guest
interactions between nanofillers and the matrix polymer films and report the
fabrication of intrinsically healable, reduced graphene oxide (RGO)-reinforced
polymer composite films capable of conveniently and repeatedly healing cuts of
several tens of micrometers wide. The healable films can be prepared via layer-by
layer assembly of poly(acrylic acid) (PAA) with complexes of branched
poly(ethylenimine) grafted with ferrocene (bPEI-Fc) and RGO nanosheets modified
with beta-cyclodextrin (RGO-CD) (denoted as bPEI-Fc&RGO-CD). The as-prepared
PAA/bPEI-Fc&RGO-CD films are mechanically robust with a Young's modulus of 17.2
+/- 1.9 GPa and a hardness of 1.00 +/- 0.30 GPa. The healing process involves two
steps: (i) healing of cuts in an oxidation condition in which the host-guest
interactions between bPEI-Fc and RGO-CD nanosheets are broken and the cuts on the
films are healed; and (ii) reconstruction of host-guest interactions between bPEI
Fc and RGO-CD nanosheets via reduction to restore the original mechanical
robustness of the films.
PMID- 28692252
TI - A Piezochromic Dysprosium(III) Single-Molecule Magnet Based on an Aggregation
Induced-Emission-Active Tetraphenylethene Derivative Ligand.
AB - A bifunctional dysprosium(III) dimer, [Dy2(HTPEIPOMe)2(OAc)4(NO3)2] (1),
comprising an AIE-active (AIE = aggregation-induced emission) ligand of 2-methoxy
6-[[[4-(1,2,2-triphenylvinyl)phenyl]imino]methyl]phenol (HTPEIPOMe), was
successfully synthesized. It not only behaves as a single-molecule magnet (SMM)
with an energy barrier of 168(15) K at zero field but also exhibits piezochromism
during the pressing-fuming cycle with switchable color, photoluminescence, and
magnetic response.
PMID- 28692253
TI - Characterizing Single Polymeric and Protein Nanoparticles with Surface Plasmon
Resonance Imaging Measurements.
AB - Near-infrared surface plasmon resonance imaging (SPRI) microscopy is used to
detect and characterize the adsorption of single polymeric and protein
nanoparticles (PPNPs) onto chemically modified gold thin films in real time. The
single-nanoparticle SPRI responses, Delta%RNP, from several hundred adsorbed
nanoparticles are collected in a single SPRI adsorption measurement. Analysis of
Delta%RNP frequency distribution histograms is used to provide information on the
size, material content, and interparticle interactions of the PPNPs. Examples
include the measurement of log-normal Delta%RNP distributions for mixtures of
polystyrene nanoparticles, the quantitation of bioaffinity uptake into and
aggregation of porous NIPAm-based (N-isopropylacrylamide) hydrogel nanoparticles
specifically engineered to bind peptides and proteins, and the characterization
of the negative single-nanoparticle SPRI response and log-normal Delta%RNP
distributions obtained for three different types of genetically encoded gas
filled protein nanostructures derived from bacteria.
PMID- 28692254
TI - Dissecting the Disulfide Linkage of the N-Terminal Domain of HMW 1Dx5 and Its
Contributions to Dough Functionality.
AB - The N-terminal domain of HMW-GS 1Dx5 (1Dx5-N) contains three cysteine residues
(Cys10, Cys25, Cys40), which are the basis of gluten network formation through
disulfide bonds. Disulfide linkage in 1Dx5-N was dissected by site-directed
mutagenesis and LC-MS/MS, and its contributions to structural and conformational
stability of 1Dx5-N and dough functionality were investigated by circular
dichroism, intrinsic fluorescence, surface hydrophobicity determination, size
exclusion chromatography, nonreducing/reducing SDS-PAGE, atomic force microscopy,
and farinographic analysis. Results showed that Cys10 and Cys40 of 1Dx5-N were
the active sites for intermolecular linkage. Meanwhile, Cys40 also exhibited the
ability to form intrachain disulfide linkage with Cys25. Moreover, Cys10 and
Cys40 played a functionally important role in maintaining the structural and
conformational stability and high surface hydrophobicity of the N-terminal domain
of HMW-GS, which in turn facilitated the formation of HMW polymers and massive
disulfide linkage of HMW-GS through hydrophobic interaction. Additionally, the
1Dx5-N mutants in which Cys were replaced by serine (Ser) presented different
effects on dough functionality, while only the C25S mutant produced positive
effects compared with wild type 1Dx5-N. Na2CO3-induced beta-elimination of
cystine might occur in glutenin without heating, which would make it much easier
to reduce the nutritional quality of flour products by the cost of lysine.
Therefore, these results give a deep understanding of the disulfide linkage of
the N-terminal domain of HMW-GS and its functional importance, which will provide
a practical guide to effectively generate a superior HMW-GS allele by artificial
mutagenesis.
PMID- 28692255
TI - Cloning, Expression, and the Effects of Processing on Sarcoplasmic-Calcium
Binding Protein: An Important Allergen in Mud Crab.
AB - Shellfish allergy is a prevalent, long-lasting disorder usually persisting
throughout life. However, the allergen information is incomprehensive in crab.
This study aimed to identify a novel allergen in crab, show its potential in
diagnosis and reduce the allergenicity by food processing. A 21-kDa protein was
purified from Scylla paramamosain and confirmed as sarcoplasmic calcium binding
protein (SCP) by matrix-assisted laser desorption ionization-time-of-flight/time
of-flight mass spectrometry (MALDI-TOF/TOF-MS). Total RNA was isolated from crab
muscle, and a rapid amplification of cDNA was performed to obtain an ORF of 579
bp that coded for 193 amino acid residues. According to the results of circular
dichroism analysis and ELISA assay, the recombinant SCP (rSCP) expressed in
Escherichia coli showed similar physicochemical and immunoreactive properties to
native SCP (nSCP). Additionally, the extensive cross reactivity of SCP among
different species and the bidirectional IgE cross-reactivity between nSCP and
rSCP were detected by iELISA. The allergenicity of rSCP was reduced via Maillard
reaction or enzymatic cross-linking reaction, which was confirmed by the results
of scanning electron microscopy, dot blot, and digestion assay. A straightforward
and reproducible way was developed to obtain high yields of rSCP that maintains
structural integrity and full IgE reactivity, which could compensate the low
specific IgE-titers of most patient sera for future diagnosis. Furthermore, the
Maillard reaction and enzymatic cross-linking reaction were effective approaches
for the production of hypoallergenic seafood.
PMID- 28692256
TI - Magnetic and Structural Studies of Sc Containing Ruthenate Double Perovskites
A2ScRuO6 (A = Ba, Sr).
AB - Ruthenium-containing double perovskites A2ScRuO6 have been synthesized as
polycrystalline powders and structurally characterized using a combination of
synchrotron X-ray and neutron powder diffraction methods. When A = Ba, a
hexagonal 6L perovskite structure is obtained if the synthesis is conducted at
ambient pressure and a rock-salt ordered cubic structure is obtained if the
sample is quenched from high pressures. The Sr oxide Sr2ScRuO6 is obtained with a
rock-salt ordered corner sharing topology. Heat capacity and bulk magnetic
susceptibility measurements show that the three oxides are antiferromagnets.
Cubic Ba2ScRuO6 undergoes a metal-insulator transition near 270 K and hexagonal
Ba2ScRuO6 is a semiconductor with an activation energy of 0.207 eV. The magnetic
structures of the two rock-salt ordered double perovskites were established using
powder neutron diffraction and are described by k = (0,0,1) and k = (0,0,0) for
the Ba and Sr oxides, respectively, corresponding to type I antiferromagnetic
structures, with ferromagnetic layers stacked antiferromagnetically. The ambient
pressure hexagonal polymorph of Ba2ScRuO6 has partial Sc-Ru ordering at both the
face-sharing B2O9 dimer and corner-sharing BO6 sites. The magnetic structure is
described by k = (1/2,0,0) with the basis vector belonging to the irreducible
representation Gamma3.
PMID- 28692257
TI - Targeting Osteocytes to Attenuate Early Breast Cancer Bone Metastasis by
Theranostic Upconversion Nanoparticles with Responsive Plumbagin Release.
AB - The early detection and thus treatment of breast cancer bone metastasis remain a
big challenge clinically. As the most abundant cells within bone tissue,
osteocytes have been found to manipulate the activity of early cancer bone
metastasis by its crosstalk with cancer cells and osteoclasts. However,
conventional bone-targeting nanomedicine has limited bone-lesion specificity and
ignores the vital role of osteocytes during breast cancer bone metastasis. Also,
it lacks detailed insight into the therapeutic mechanisms, which hinders the
following translational practice. Previously, we have shown that a combination of
zoledronic acid (ZA) and plumbagin (PL) synergistically alleviates cancer-induced
bone destruction. Herein, we further develop a pH-responsive bone-targeting drug
delivery system, i.e., the ZA-anchored bimodal mesoporous slica covered
gadolinium(III) upconversion nanoparticles loaded with PL, to detect and treat
bone metastasis sensitively and specifically at an early stage. This
multifunctional nanosystem can target osteocytes to release PL as controlled by
pH, decreasing osteocytic RANKL expression synergistically through the structural
simulation of adenosine phosphate, which competitively inhibits the
phosphorylation of osteocytic protein kinase-a, cAMP-response element binding
protein, extracellular regulated protein kinase, and c-Jun N-terminal kinase.
More importantly, by establishing a breast cancer bone metastasis mice model via
intracardiac injection, we show that tumoriogenesis and osteoclastogenesis can
both be attenuated significantly. We thereby realize the effective theranostics
of tiny bone metastasis in breast cancer bone metastasis. Our work highlights the
significance of theranostic nanomedicine and osteocyte-targeting therapy in the
treatment of early bone metastasis, which could be applied in achieving efficient
theranostic effects for other bone diseases.
PMID- 28692258
TI - Discrimination between Synthetically Administered and Endogenous Thiouracil Based
on Monitoring of Urine, Muscle, and Thyroid Tissue: An in Vivo Study in Young and
Adult Bovines.
AB - Thiouracil (TU), synthesized for its thyroid-regulating capacities and
alternatively misused in livestock for its weight-gaining effects, is
acknowledged to have an endogenous origin. Discrimination between low-level abuse
and endogenous occurrence is challenging and unexplored in an experimental
setting. Therefore, cows (n = 16) and calves (n = 18) were subjected to a
rapeseed-supplemented diet or treated with synthetic TU. Significant higher
urinary TU levels were recorded after TU administration ( 7FJ emission. For both compounds, the triplet and
5D2 states were determined at the CASPT2 level to be around ~26000 and ~22400 cm
1, respectively. This difference is in the optimal range for the energy transfer
process. Finally, the emissive state 5D0 was found at ~18000 cm-1 and the
emission bands in the range 550-700 nm, in quite good agreement with the
experimental results.
PMID- 28692260
TI - Chemo- and Regioselective Organo-Photoredox Catalyzed Hydroformylation of
Styrenes via a Radical Pathway.
AB - An unprecedented, chemo- and regioselective, organo-photoredox catalyzed
hydroformylation reaction of aryl olefins with diethoxyacetic acid as the
formylation reagent is described. In contrast to traditional transition metal
promoted ionic hydroformylation reactions, the new process follows a unique
photoredox promoted, free radical pathway. In this process, a formyl radical
equivalent, produced from diethoxacetic acid through a dye (4CzIPN)
photocatalyzed, sequential oxidation-decarboxylation route, regio- and
chemoselectively adds to a styrene substrate. Importantly, under the optimized
reaction conditions the benzylic radical formed in this manner is reduced by SET
from the anion radical of 4CzIPN to generate a benzylic anion. Finally,
protonation produces the hydroformylation product. By using the new protocol,
aldehydes can be generated regioselectively in up to 90% yield. A broad array of
functional groups is tolerated in the process, which takes place under mild,
metal-free conditions.
PMID- 28692261
TI - High Antioxidant Action and Prebiotic Activity of Hydrolyzed Spent Coffee Grounds
(HSCG) in a Simulated Digestion-Fermentation Model: Toward the Development of a
Novel Food Supplement.
AB - Spent coffee grounds are a byproduct with a large production all over the world.
The aim of this study was to explore the effects of a simulated digestion
fermentation treatment on hydrolyzed spent coffee grounds (HSCG) and to
investigate the antioxidant properties of the digestion and fermentation products
in the human hepatocellular carcinoma HepG2 cell line. The potentially
bioaccessible (soluble) fractions exhibited high chemoprotective activity in
HepG2 cells against oxidative stress. Structural analysis of both the
indigestible (insoluble) and soluble material revealed partial hydrolysis and
release of the lignin components in the potentially bioaccessible fraction
following simulated digestion-fermentation. A high prebiotic activity as
determined from the increase in Lactobacillus spp. and Bifidobacterium spp. and
the production of short-chain fatty acids (SCFAs) following microbial
fermentation of HSCG was also observed. These results pave the way toward the use
of HSCG as a food supplement.
PMID- 28692262
TI - Family of Ricinus communis Monosaccharide Transporters and RcSTP1 in Promoting
the Uptake of a Glucose-Fipronil Conjugate.
AB - Enhancing the systemic distribution of a bioactive compound by exploiting the
vascular transport system of a plant presents a means of reducing both the volume
and frequency of pesticide/fungicide application. The foliar uptake of the
glucose-fipronil conjugate N-[3-cyano-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]
4-[(trifluoromethyl)sulfinyl]-1H-pyrazol-5-yl]-1-(beta-d-glucopyranosyl)-1H-1,2,3
triazole-4-methanamine (GTF) achieved in castor bean (Ricinus communis) and its
transport via the phloem are known to be mediated by monosaccharide
transporter(s) [MST(s)], although neither the identity of the key MST(s) involved
nor the mechanistic basis of its movement have yet to be described. On the basis
of homology with Arabidopsis thaliana sugar transporters, the castor bean genome
was concluded to harbor 53 genes encoding a sugar transporter, falling into the
eight previously defined subfamilies INT, PMT, VGT, STP, ERD6, pGlucT, TMT, and
SUT. Transcriptional profiling identified the product of RcSTP1 as a candidate
for mediating GTF uptake, because this gene was induced by exposure of the plant
to GTF. When RcSTP1 was transiently expressed in onion epidermis cells, the site
of RcSTP1 deposition was shown to be the plasma membrane. A functional analysis
based on RcSTP1 expression in Xenopus laevis oocytes demonstrated that its
product has a high affinity for GTF. The long-distance root-to-shoot transport of
GTF was enhanced in a transgenic soybean chimera constitutively expressing
RcSTP1.
PMID- 28692263
TI - Dramatic Differences in Aggregation-Induced Emission and Supramolecular
Polymerizability of Tetraphenylethene-Based Stereoisomers.
AB - Geometric (Z)- and (E)-isomers play important but different roles in life and
material science. The design of new (Z)-/(E)- isomers and study of their
properties, behaviors, and interactions are crucially important in molecular
engineering. However, difficulties with their separation and structure
confirmation limit their structural diversity and functionality in scope. In the
work described herein, we successfully synthesized pure isomers of
ureidopyrimidinone-functionalized tetraphenylethenes ((Z)-TPE-UPy and (E)-TPE
UPy), featuring both the aggregation-induced emission characteristic of
tetraphenylethene and the supramolecular polymerizability of ureidopyrimidinone.
Their structures were confirmed by 2D COSY and NOESY NMR spectroscopies. The two
isomers show distinct fluorescence in the aggregate state: (Z)-TPE-UPy exhibits
green emission, while its (E)-counterpart is blue-emitting. The cavity formed by
the two ureidopyrimidinone groups of (Z)-TPE-UPy makes it suitable for Hg2+
detection, and the high-molecular-weight polymers prepared from (E)-TPE-UPy can
be used to fabricate highly fluorescent fibers and 2D/3D photopatterns from their
chloroform solutions.
PMID- 28692264
TI - Phenolic Responses to Esca-Associated Fungi in Differently Decayed Grapevine
Woods from Different Trunk Parts of 'Cabernet Sauvignon'.
AB - Alterations in phenolic contents were studied in Esca symptomatic (Sym) and
asymptomatic (Asym) vines of 'Cabernet Sauvignon' based on wood conditions
(healthy, HLT; necrotic, Nec; and rotten, Rot) and vine parts (head, trunk, and
rootstock). In Asym vines, only Alternaria alternate was identified in Nec wood,
while the HLT wood of Sym vines was colonized by Botryospaeriaceae sp. and
Aureobasidium pullulans, Nec wood by Fomitiporia mediterranea, and Rot wood by
Fomitiporia mediterranea and Phaeomoniella chlamydospora. Esca infection caused a
significant accumulation of gallic acid, total flavanols, stilbenes (STB), and
total analyzed phenolics (TAP) in all studied woods, especially in Nec wood. In
Asym vines, TAP in the head increased with necrosis, but in Sym it decreased,
while TAP in the trunk and rootstock of Sym showed an opposite response. The
significantly highest contents of procyanidins (Pcys), catechin, epicatechin,
epicatechin gallates, and Pcys dimers and tetramers were measured in HLT wood in
the head and in Nec wood in the trunk of Sym vines. The significant increase of
STB content was not caused only by Esca infection in HLT wood but also by
necrosis in Asym vines, especially of epsilon-viniferin glucoside, resveratrol
glycosides, and astringin. The obtained results suggest that the alteration in
phenolics differed not only due to Esca infection but also due to the wood
conditions and vine part, which might reflect the impact of the duration of the
presence of the pathogen in different parts of the vine.
PMID- 28692265
TI - Understanding Divergent Thermal Conductivity in Single Polythiophene Chains Using
Green-Kubo Modal Analysis and Sonification.
AB - We used molecular dynamics simulations and the Green-Kubo modal analysis (GKMA)
method as well as sonification to study the modal contributions to thermal
conductivity in individual polythiophene chains. The simulations suggest that it
is possible to achieve divergent thermal conductivity in individual polythiophene
chains of certain lengths, with periodic boundary conditions. Application of the
GKMA method further allowed for exact pinpointing of the modes responsible for
the anomalous behavior. The analysis showed that transverse vibrations in the
plane of the aromatic rings at low frequencies ~0.05 THz are primarily
responsible for the divergence. Within the integration time, one mode in
particular exhibits a thermal conductivity contribution greater than 100 W m-1 K
1. Further investigation showed that the divergence arises from persistent
correlation between the three lowest frequency modes on chains that have exact
multiples of 30 unit cells in length. Sonification of the mode heat fluxes
revealed regions where the heat flux amplitude yields a somewhat sinusoidal
envelope with a long period similar to the relaxation time. This characteristic
in the divergent mode heat fluxes gives rise to the overall thermal conductivity
divergence, which strongly supports earlier hypotheses that attribute the
divergence to correlated phonon-phonon scattering/interactions as opposed to a
lack of scattering/interaction among modes (e.g., infinite relaxation
time/ballistic transport).
PMID- 28692266
TI - SlMAPK1/2/3 and Antioxidant Enzymes Are Associated with H2O2-Induced Chilling
Tolerance in Tomato Plants.
AB - Hydrogen peroxide (H2O2) acts as a signaling molecule in response to cold stress.
Mitogen-activated protein kinases (MAPKs) and C-repeat/dehydration-responsive
factor (CBF) play important roles in cold response regulation. To investigate the
roles of MAPKs and CBF in H2O2-induced chilling tolerance, tomato (Solanum
lycopersicum cv. Ailsa Craig) plants were treated with 1 mM H2O2 before chilling
treatment. The results showed that H2O2 treatment protected subcellular
structure, increased concentrations of abscisic acid (ABA), zeatin riboside (ZR),
and methyl jasmonate (MeJA), but decreased the concentration of gibberellic acid
(GA3). Furthermore, 1 mM H2O2 treatment enhanced the activities of antioxidant
enzymes. Meanwhile, relative expressions of SlMAPK1/2/3 and SlCBF1 in H2O2
treated plants were higher than those in the control. Our findings suggest that
H2O2 treatment might enhance the chilling tolerance of tomato plants by
activating SlMAPK1/2/3 and SlCBF1 gene expression and by regulating phytohormone
concentrations and antioxidant enzyme activities.
PMID- 28692267
TI - Is Multitask Deep Learning Practical for Pharma?
AB - Multitask deep learning has emerged as a powerful tool for computational drug
discovery. However, despite a number of preliminary studies, multitask deep
networks have yet to be widely deployed in the pharmaceutical and biotech
industries. This lack of acceptance stems from both software difficulties and
lack of understanding of the robustness of multitask deep networks. Our work aims
to resolve both of these barriers to adoption. We introduce a high-quality open
source implementation of multitask deep networks as part of the DeepChem open
source platform. Our implementation enables simple python scripts to construct,
fit, and evaluate sophisticated deep models. We use our implementation to analyze
the performance of multitask deep networks and related deep models on four
collections of pharmaceutical data (three of which have not previously been
analyzed in the literature). We split these data sets into train/valid/test using
time and neighbor splits to test multitask deep learning performance under
challenging conditions. Our results demonstrate that multitask deep networks are
surprisingly robust and can offer strong improvement over random forests. Our
analysis and open-source implementation in DeepChem provide an argument that
multitask deep networks are ready for widespread use in commercial drug
discovery.
PMID- 28692268
TI - Photoinduced Structural Dynamics of Molecular Systems Mapped by Time-Resolved X
ray Methods.
AB - We review the tremendous advances in ultrafast X-ray science, over the past 15
years, making the best use of new ultrashort X-ray sources including table-top or
large-scale facilities. Different complementary X-ray-based techniques, including
spectroscopy, scattering, and diffraction, are presented. The broad and expanding
spectrum of these techniques in the ultrafast time domain is delivering new
insight into the dynamics of molecular systems, of solutions, of solids, and of
biosystems. Probing the time evolution of the electronic and structural degrees
of freedom of these systems on the time scales of femtosecond to picoseconds
delivers new insight into our understanding of dynamical matter.
PMID- 28692269
TI - Unimolecular Decay of the Dimethyl-Substituted Criegee Intermediate in Alkene
Ozonolysis: Decay Time Scales and the Importance of Tunneling.
AB - We used the steady-state master equation to model unimolecular decay of the
Criegee intermediate formed from ozonolysis of 2,3-dimethyl-2-butene
(tetramethylethylene, TME). Our results show the relative importance and time
scales for both the prompt and thermal unimolecular decay of the dimethyl
substituted Criegee intermediate, (CH3)2COO. Calculated reactive fluxes show the
importance of quantum mechanical tunneling for both prompt and thermal decay to
OH radical products. We constrained the initial energy distribution of chemically
activated (CH3)2COO formed in TME ozonolysis by combining microcanonical rates
k(E) measured experimentally under collision-free conditions and modeled using
semiclassical transition-state theory (SCTST) with pressure-dependent yields of
stabilized Criegee intermediates measured with scavengers in flow-tube
experiments. Thermal decay rates under atmospheric conditions k(298 K, 1 atm)
increase by more than 1 order of magnitude when tunneling is included. Accounting
for tunneling has important consequences for interpreting pressure dependent
yields of stabilized Criegee intermediates, particularly with regard to the
fraction of Criegee intermediates formed in the zero-pressure limit.
PMID- 28692270
TI - Dispersion of the Photosensitizer 5,10,15,20-Tetrakis(4-Sulfonatophenyl)
porphyrin by the Amphiphilic Polymer Poly(vinylpirrolidone) in Highly Porous
Solid Materials Designed for Photodynamic Therapy.
AB - The ability of the amphiphilic and biocompatible poly(vinylpyrrolidone) to avoid
self-aggregation of the photosensitizer 5,10,15,20-tetrakis(4
sulfonatophenyl)porphyrin in aqueous solution in the presence of the
biocompatible polycation chitosan, polymer that induces the dye self-aggregation,
is shown. This is related to the tendency of the dye to undergo preferential
solvation by the amphiphilic polymer. Importantly, the dispersant ability of this
polymer is transferred to the solid state. Thus, aerogels made of the
biocompatible polymers chitosan and chondroitin sulfate, and containing the
photosensitizer dispersed by the amphiphilic polymer have been synthesized.
Production of reactive oxygen species by the aerogel containing the amphiphilic
polymer was faster than when the polymer was absent, correlating with the
relative concentration of dyes dispersed as monomers. The aerogels presented here
constitute low cost biocompatible materials bearing a conventional
photosensitizer for photodynamic therapy, easy to produce, store, transport, and
manage in clinical practice.
PMID- 28692271
TI - Benchmark ab Initio Characterization of the Complex Potential Energy Surface of
the Cl- + CH3I Reaction.
AB - Benchmark stationary-point structures, vibrational frequencies, and
classical/adiabatic relative energies (kcal/mol) are reported for the Cl- + CH3I
reaction along the back-side attack (DeltaETS = -5.48/-5.54) inversion, front
side attack (DeltaETS = 36.73/35.89) and double-inversion (DeltaETS =
46.97/42.55) retention SN2 pathways, the proton-transfer channel, and the hydride
substitution reaction path. The structures and frequencies are obtained by the
frozen-core CCSD(T), CCSD(T)-F12a, and CCSD(T)-F12b methods with the aug-cc-pVnZ
[n = D, T, and Q for structures and n = D and T for frequencies] basis sets and
all-electron CCSD(T) with aug-cc-pwCVnZ [n = D and T for structures and n = D for
frequencies]. The benchmark relative energies are determined using the focal
point analysis approach based on electron correlation methods up to CCSDT(Q),
extrapolations to the complete basis set limits using aug-cc-pVnZ [n = 2(D),
3(T), 4(Q), and 5] bases, core correlation contributions obtained at CCSD(T)/aug
cc-pwCVQZ, and, for the adiabatic energies, zero-point energy corrections at the
CCSD(T)-F12b/aug-cc-pVTZ level of theory. We usually find significant method and
modest basis dependence for the energies. The post-CCSD(T) and core correlation
effects are often about 0.4 kcal/mol, but almost cancel each other. The
explicitly correlated CCSD(T)-F12 methods are recommended for geometry and
frequency computations as well as for energy computations if the basis set
dependence is significant.
PMID- 28692272
TI - Spirograterpene A, a Tetracyclic Spiro-Diterpene with a Fused 5/5/5/5 Ring System
from the Deep-Sea-Derived Fungus Penicillium granulatum MCCC 3A00475.
AB - A novel spiro-tetracyclic diterpene, spirograterpene A (1), was isolated from the
deep-sea-derived fungus Penicillium granulatum MCCC 3A00475, together with two
biosynthetically related cyclopianes, conidiogenone I (2) and conidiogenone C
(3). The relative configuration of 1 was elucidated by extensive spectroscopic
analyses, and the absolute structure was established by the modified Mosher's
method. Compound 1 is the second example of a diterpene featuring a 5/5/5/5
spirocyclic carbon skeleton. It showed modest antiallergic activity.
PMID- 28692273
TI - Protein Mixture Segregation at Coffee-Ring: Real-Time Imaging of Protein Ring
Precipitation by FTIR Spectromicroscopy.
AB - During natural drying process, all solutions and suspensions tend to form the so
called "coffee-ring" deposits. This phenomenon, by far, has been interpreted by
the hydrodynamics of evaporating fluids. However, in this study, by applying
Fourier transform infrared imaging (FTIRI), it is possible to observe the
segregation and separation of a protein mixture at the "ring", hence we suggest a
new way to interpret "coffee-ring effect" of solutions. The results explore the
dynamic process that leads to the ring formation in case of model plasma
proteins, such as BGG (bovine gamma globulin), BSA (bovine serum albumin), and
Hfib (human fibrinogen), and also report fascinating discovery of the segregation
at the ring deposits of two model proteins BGG and BSA, which can be explained by
an energy kinetic model, only. The investigation suggests that the coffee-ring
effect of solute in an evaporating solution drop is driven by an energy gradient
created from change of particle-water-air interfacial energy configuration.
PMID- 28692274
TI - Solid-State 15N and 17O NMR Studies of S-Nitrosothiols.
AB - We report a solid-state 15N and 17O NMR study of two representative S
nitrosothiols (RSNO): S-nitroso N-acetylpenicillamine (SNAP) and S
nitrosoglutathione (GSNO). The 15N and 17O NMR tensors are experimentally
determined for the first time for this important class of nitric-oxide (NO)
related compounds. The observed NMR characteristics for RSNO include large 15N
and 17O chemical shift anisotropies and large 17O quadrupole coupling constants.
Quantum chemical calculations are also performed for the 15N and 17O NMR tensors
in two simple RSNO models: t-BuSNO and MeSNO. On the basis of computational
results, we have identified the molecular orbitals that are responsible for the
observed large chemical shift anisotropies in RSNO compounds.
PMID- 28692275
TI - Gold-Catalyzed Cascade Reaction of Skipped Diynes for the Construction of a
Cyclohepta[b]pyrrole Scaffold.
AB - A gold-catalyzed cascade reaction of skipped diynes (1,4-diynes) and pyrroles has
been developed. This reaction proceeds by the consecutive regioselective
hydroarylation of two alkynes with a pyrrole, followed by a 7-endo-dig
cyclization to give 1,6-dihydrocyclohepta[b]pyrroles in good yields. The direct
synthesis of cyclohepta[b]indoles using indole nucleophiles has also been
reported.
PMID- 28692276
TI - Cooperativity Scale: A Structure-Mechanism Correlation in the Self-Assembly of
Benzene-1,3,5-tricarboxamides.
AB - The self-assembly of small and well-defined molecules using noncovalent
interactions to generate various nano- and microarchitectures has been
extensively studied. Among various architectures, one-dimensional (1-D) nano
objects have garnered significant attention. It has become increasingly evident
that a cooperative or nucleation-elongation mechanism of polymerization leads to
highly ordered 1-D supramolecular polymers, analogous to shape-persistent
biopolymers such as actin. With this in mind, achieving cooperativity in self
assembled structures has been actively pursued with significant success. Only
recently, researchers are focusing on the origin of the mechanism at the
molecular level in different synthetic systems. Taking a step further, a thorough
quantitative structure-mechanism correlation is crucial to control the size,
shape, and functions of supramolecular polymers, and this is currently lacking in
the literature. Among a plethora of molecules, benzene-1,3,5-tricarboxamides
(BTAs) provide a unique combination of important noncovalent interactions such as
hydrogen bonding, pi-stacking, and hydrophobic interactions, for self-assembly
and synthetic ease. Due to the latter, a diverse range of BTA derivatives with
all possible structural mutations have been synthesized and studied during the
past decade, mainly from our group. With such a large body of experimental
results on BTA self-assembly, it is time to embark on a structure-mechanism
correlation in this family of molecules, and a first step toward this will form
the main focus of this Account. The origin of the cooperative mechanism of self
assembly in BTAs has been ascribed to 3-fold intermolecular hydrogen bonding (HB)
between monomers based on density-functional theory (DFT) calculations. The
intermolecular hydrogen-bonding interaction forms the central premise of this
work, in which we evaluate the effect of different moieties such as alkyl chains,
and amino acids, attached to the core amides on the strength of intermolecular
HB, which consequently governs the extent of cooperativity (quantified by the
cooperativity factor, sigma). In addition to this, we evaluate the effect of
amide connectivity (C- vs N-centered), the role of solvents, amides vs
thioamides, and finally the influence of the benzene vs cyclohexane core on the
sigma. Remarkably, every subtle structural change in the BTA monomer seems to
affect the cooperativity factor in a systematic and rationalizable way. The take
home message will be that the cooperativity factor (sigma) in the BTA family
forms a continuous spectrum from 1 (isodesmic) to <10-6 (highly cooperative) and
it can be tuned based on the appropriate modification of the BTA monomer. We
anticipate that these correlations drawn from the BTA series will be applicable
to other systems in which HB is the main driving force for cooperativity. Thus,
the understanding gained from such correlations on a prototypical self-assembling
motif such as BTA will aid in designing more complex systems with distinct
functions.
PMID- 28692277
TI - Aromatically C6- and C9-Substituted Phenanthro[9,10-d]imidazole Blue
Fluorophores: Structure-Property Relationship and Electroluminescent Application.
AB - In this study, a series of aromatically substituted phenanthro[9,10-d]imidazole
(PI) fluorophores at C6 and C9 (no. 6 and 9 carbon atoms) have been synthesized
and systematically characterized by theoretical, thermal, photophysical,
electrochemical, and electroluminescent (EL) studies. C6 and C9 modifications
have positive influences on the thermal properties of the new materials.
Theoretical calculations suggest that the C6 and the C9 positions of PI are
electronically different. Theoretical and experimental evidences of
intramolecular charge transfer (ICT) between two identical moieties attaching to
the C6 and the C9 positions are observed. Photophysical properties of the
fluorophores are greatly influenced by size and conjugation extent of the
substituents as well as linking steric hindrance. It is found that the C6 and C9
positions afford moderate conjugated extension compared to the C2 modification.
Moreover, ICT characteristics of the new fluorophores increase as the size of the
substituted aromatic group, and are partially influenced by steric hindrance,
with the anthracene and the pyrene derivatives having the strongest ICT excited
properties. EL performances of the fluorophores were evaluated as host emitters
or dopants in organic light-emitting devices (OLEDs). Most of the devices showed
significantly improved efficiencies compared to the OLED using the nonmodified
emitter. Among all the devices, a 5 wt % TPI-Py doped device exhibited excellent
performances with an external quantum efficiency >5% at 1000 cd/m2 and a deep
blue color index of (0.155, 0.065), which are comparable to the most advanced
deep-blue devices. Our study can give useful information for designing C6/C9
modificated PI fluorophores and provide an efficient approach for constructing
high-performance deep-blue OLEDs.
PMID- 28692278
TI - Ab Initio Calculations of Ultrashort Carrier Dynamics in Two-Dimensional
Materials: Valley Depolarization in Single-Layer WSe2.
AB - In single-layer WSe2, a paradigmatic semiconducting transition metal
dichalcogenide, a circularly polarized laser field can selectively excite
electronic transitions in one of the inequivalent K+/- valleys. Such selective
valley population corresponds to a pseudospin polarization. This can be used as a
degree of freedom in a "valleytronic" device provided that the time scale for its
depolarization is sufficiently large. Yet, the mechanism behind the valley
depolarization still remains heavily debated. Recent time-dependent Kerr
experiments have provided an accurate way to visualize the valley dynamics by
measuring the rotation of a linearly polarized probe pulse applied after a
circularly polarized pump pulse. We present here a clear, accurate and parameter
free description of the valley dynamics. By using an atomistic, ab initio
approach, we fully disclose the elemental mechanisms that dictate the
depolarization effects. Our results are in excellent agreement with recent time
dependent Kerr experiments. We explain the Kerr dynamics and its temperature
dependence in terms of electron-phonon-mediated processes that induce spin-flip
intervalley transitions.
PMID- 28692279
TI - Hot-Electron Intraband Luminescence from GaAs Nanospheres Mediated by Magnetic
Dipole Resonances.
AB - Significantly enhanced electric field in plasmonic hot spots can dramatically
increase the linear and nonlinear absorption of light, leading to a high
temperature electron gas which radiates, through mainly intraband transition, a
broadband luminescence quite similar to blackbody radiation. Here, we demonstrate
that such hot-electron intraband luminescence (HEIL) can also be achieved by
exploiting the significantly enhanced electric field at the magnetic dipole
resonances of gallium arsenide (GaAs) nanospheres (NSs). We show that
monocrystalline GaAs NSs with distinct electric and magnetic dipole (ED and MD)
resonances can be obtained by using femtosecond laser ablation and annealing.
Significantly enhanced second harmonic generation and broadband HEIL are observed
when the MD resonances of such GaAs NSs are resonantly excited. The lifetime of
the HEIL is found to be as short as ~82 ps, indicating a significant enhancement
in radiative intraband transition rate. We reveal that the slope extracted from
the dependence of the HEIL intensity on the irradiance is linearly proportional
to the energy of the emitted photon. The existence of distinct ED and MD
resonances in combination with a direct bandgap makes GaAs NSs an attractive
candidate for constructing novel all-dielectric metamaterials and active photonic
devices.
PMID- 28692280
TI - Revealing Nanoscale Passivation and Corrosion Mechanisms of Reactive Battery
Materials in Gas Environments.
AB - Lithium (Li) metal is a high-capacity anode material (3860 mAh g-1) that can
enable high-energy batteries for electric vehicles and grid-storage applications.
However, Li metal is highly reactive and repeatedly consumed when exposed to
liquid electrolyte (during battery operation) or the ambient environment
(throughout battery manufacturing). Studying these corrosion reactions on the
nanoscale is especially difficult due to the high chemical reactivity of both Li
metal and its surface corrosion films. Here, we directly generate pure Li metal
inside an environmental transmission electron microscope (TEM), revealing the
nanoscale passivation and corrosion process of Li metal in oxygen (O2), nitrogen
(N2), and water vapor (H2O). We find that while dry O2 and N2 (99.9999 vol %)
form uniform passivation layers on Li, trace water vapor (~1 mol %) disrupts this
passivation and forms a porous film on Li metal that allows gas to penetrate and
continuously react with Li. To exploit the self-passivating behavior of Li in dry
conditions, we introduce a simple dry-N2 pretreatment of Li metal to form a
protective layer of Li nitride prior to battery assembly. The fast ionic
conductivity and stable interface of Li nitride results in improved battery
performance with dendrite-free cycling and low voltage hysteresis. Our work
reveals the detailed process of Li metal passivation/corrosion and demonstrates
how this mechanistic insight can guide engineering solutions for Li metal
batteries.
PMID- 28692282
TI - Design and Applications of Metastable-State Photoacids.
AB - Proton transfer is one of the most common processes in nature, and many chemical,
material, and biological processes are sensitive to proton concentration, from
acid-catalyzed reactions to the activities of many enzymes. Photoacids that
reversibly undergo proton dissociation upon irradiation promise remote spatial
and temporal control over proton-sensitive processes and could provide a way to
convert photoenergy into other types of energy. The recently discovered
metastable-state photoacids can produce a large proton concentration with high
efficiency and good reversibility. A reversible pH change of over 2 units has
been demonstrated using an aqueous solution of a metastable-state photoacid.
Additionally, moderate-intensity visible light, for example, from LEDs and
sunlight, can be used to activate this type of photoacid. This photocontrolled
proton release occurs in aqueous and nonaqueous solutions and in polymeric
materials. Therefore, this type of photoacid can be conveniently incorporated
into different systems to control various proton transfer processes. Metastable
state photoacids are generally designed by linking an electron-accepting moiety
and a weakly acidic nucleophilic moiety with a double bond. Photoinduced trans
cis isomerization of the double bond allows a nucleophilic cyclization reaction
to occur between the two moieties. The tandem reaction generates a highly acidic
metastable form, which releases a proton. In the dark, the metastable form
relaxes to the original form and takes back the proton. Several electron
accepting and nucleophilic moieties have been used to construct different types
of metastable-state photoacids for different applications. The advantages and
disadvantages of these photoacids in terms of their photoacidity, dark acidity,
reversibility, stability, etc. will be discussed in this Account. Metastable
state photoacids have been used to catalyze bond formation and bond-breaking
reactions in which the reactions can be activated and stopped by turning on and
off irradiation, respectively. They have been used to reversibly protonate
molecules to affect the ionic and hydrogen bonding between molecules or between
different moieties of a molecule. Protonation can also alter the electronic
configuration of molecules to change their electronic and optical properties.
Since a proton has a positive charge, photoacids have been used to control ion
exchange processes. Applying metastable-state photoacids to control Fisher
esterification, volume-changing hydrogels, the killing of bacteria, odorant
release, the color of materials, the formation of nanoparticles, and polymer
conductivity has been reported by our group. Metastable-state photoacids have
also been utilized to control supramolecular assemblies, molecular switches,
microbial fuel cells, cationic sensors, nanoparticle aggregation, and ring
opening polymerizations. The future prospects of this research area will be
discussed at the end of this Account.
PMID- 28692281
TI - Structural and Biophysical Characterization of the Mycobacterium tuberculosis
Protein Rv0577, a Protein Associated with Neutral Red Staining of Virulent
Tuberculosis Strains and Homologue of the Streptomyces coelicolor Protein KbpA.
AB - Mycobacterium tuberculosis protein Rv0577 is a prominent antigen in tuberculosis
patients, the component responsible for neutral red staining of virulent strains
of M. tuberculosis, a putative component in a methylglyoxal detoxification
pathway, and an agonist of toll-like receptor 2. It also has an amino acid
sequence that is 36% identical to that of Streptomyces coelicolor AfsK-binding
protein A (KbpA), a component in the complex secondary metabolite pathways in the
Streptomyces genus. To gain insight into the biological function of Rv0577 and
the family of KpbA kinase regulators, the crystal structure for Rv0577 was
determined to a resolution of 1.75 A, binding properties with neutral red and
deoxyadenosine were surveyed, backbone dynamics were measured, and thermal
stability was assayed by circular dichroism spectroscopy. The protein is composed
of four approximate repeats with a betaalphabetabetabeta topology arranged
radially in consecutive pairs to form two continuous eight-strand beta-sheets
capped on both ends with an alpha-helix. The two beta-sheets intersect in the
center at roughly a right angle and form two asymmetric deep "saddles" that may
serve to bind ligands. Nuclear magnetic resonance chemical shift perturbation
experiments show that neutral red and deoxyadenosine bind to Rv0577. Binding to
deoxyadenosine is weaker with an estimated dissociation constants of 4.1 +/- 0.3
mM for saddle 1. Heteronuclear steady-state {1H}-15N nuclear Overhauser effect,
T1, and T2 values were generally uniform throughout the sequence with only a few
modest pockets of differences. Circular dichroism spectroscopy characterization
of the thermal stability of Rv0577 indicated irreversible unfolding upon heating
with an estimated melting temperature of 56 degrees C.
PMID- 28692283
TI - Largely Improved Near-Infrared Silicon-Photosensing by the Piezo-Phototronic
Effect.
AB - Although silicon (Si) devices are the backbone of modern (opto-)electronics,
infrared Si-photosensing suffers from low-efficiency due to its limitation in
light-absorption. Here, we demonstrate a large improvement in the performance,
equivalent to a 366-fold enhancement in photoresponsivity, of a Si-based near
infrared (NIR) photodetector (PD) by introducing the piezo-phototronic effect via
a deposited CdS layer. By externally applying a -0.150/00 compressive strain to
the heterojunction, carrier-dynamics modulation at the local junction can be
induced by the piezoelectric polarization, and the photoresponsivity and
detectivity of the PD exhibit an enhancement of two orders of magnitude, with the
peak values up to 19.4 A/W and 1.8 * 1012 cm Hz1/2/W, respectively. The obtained
maximum responsivity is considerably larger than those of commercial Si and
InGaAs PDs in the NIR waveband. Meanwhile, the rise time and fall time are
reduced by 84.6% and 76.1% under the external compressive strain. This work
provides a cost-effective approach to achieve high-performance NIR photosensing
by the piezo-phototronic effect for high-integration Si-based optoelectronic
systems.
PMID- 28692284
TI - Variation of the Contact Time of Droplets Bouncing on Cylindrical Ridges with
Ridge Size.
AB - Reducing the contact time between bouncing droplets and an underlying solid
surface is relevant to a broad range of industrial applications, such as anti
icing and self-cleaning. Previous work has found that placing cylindrical
obstacles on the substrate leads to a reduction in contact time. For obstacles
large compared to the drop, this is a result of hydrodynamic coupling between the
azimuthal and axial spreading directions. For obstacles small compared to the
drop, the reduction in contact time is interpreted as being due to fast
retraction along the cylindrical ridge, followed by drop breakup. Here we use
simulations to discuss in greater detail the effect of varying the obstacle size
on the dynamics of the drop bouncing. We investigate the crossover between the
two regimes and explain why the contact time is minimized when the radii of the
drop and the cylindrical obstacle are comparable.
PMID- 28692285
TI - Raman Optical Activity Reveals Carotenoid Photoactivation Events in the Orange
Carotenoid Protein in Solution.
AB - The orange carotenoid protein (OCP) plays an important role in photoprotection in
cyanobacteria, which is achieved by the photoconversion from the orange dark
state (OCPO) to the red active state (OCPR). Using Raman optical activity (ROA),
we studied the conformations of the carotenoid chromophore in the active sites of
OCPO and OCPR. This ROA measurement directly observed the chromophore
conformation of native OCP in solution, and the measurement of OCPR first
demonstrated the ROA spectroscopy for the transient species. For OCPO, the
spectral features of ROA were mostly reproduced by the quantum chemical
calculation based on the crystal structure of the OCP. Within the spatial
resolution (~2 A), a slight modification of the polyene-chain distortion improved
the agreement between the observed and calculated ROA spectra. While the crystal
structure of OCPR is not available, the ROA spectrum of OCPR was reproduced by
using the crystal structure of red carotenoid protein (RCP), an OCPR proxy. The
present results showed that the chromophore conformations in the crystal
structures of OCP and RCP hold true for OCPO and OCPR in solution. Particularly,
ROA spectroscopy of the native OCPR provides a direct support for the 12 A
translocation of chromophore in the photoactivation, which was proposed by X-ray
crystallography using RCP [R. L. Leverenz, M. Sutter, et al. Science 2015, 348,
1463-1466].
PMID- 28692286
TI - Methylated Cytosine Maintains G-Quadruplex Structures during Polymerase Chain
Reaction and Contributes to Allelic Dropout.
AB - The promoter of the human imprinted gene MEST is differentially methylated with
respect to the parent of origin and contains several non B-DNA motifs that are
capable of forming G-quadruplexes. These factors can contribute to a consistent
allelic dropout (ADO) of the maternally methylated DNA during polymerase chain
reaction (PCR) analysis of such gene regions. Here, we directly investigate the
cause of allelic dropout by applying fluorescent techniques to visualize
polymerase amplification and arrest during PCR of differentially methylated DNA
templates. We demonstrate that polymerase arrest corresponds to previously
characterized G-quadruplex-forming motifs at the MEST promoter region and occurs
at equivalent sites on both methylated and nonmethylated DNA templates. However,
during PCR, polymerase arrest can be observed on the methylated template for
several cycles longer than on the nonmethylated template, and this results in an
amplification lag and a lower yield of full length amplicons. We demonstrate that
this delay in amplification is sufficient to cause complete ADO during PCR,
providing a mechanistic basis for the previously observed genotyping error at
this locus.
PMID- 28692287
TI - Quantifying the Structure and Composition of Flocculated Suspended Particulate
Matter Using Focused Ion Beam Nanotomography.
AB - Suspended particulate matter (SPM) is present in the natural aquatic environment
as loosely bound aggregates or "flocs" and is responsible for the transport and
fate of sediment, carbon, nutrients, pollutants, pathogens and manufactured
nanoparticles from catchment to coast. Accurate prediction of SPM hydrodynamics
requires the quantification of 3D floc properties (size, shape, density and
porosity) that span several spatial scales. Yet, current techniques (video camera
systems, optical microscopy and transmission electron microscopy, TEM) can only
provide 2D simplifications of size and shape with a spatial resolution gap
between the "gross" (>100s MUm) and nanoscale (<1 MUm). Here, we translate 3D
microscopy techniques (focused ion beam nanotomography, FIB-nt) typically used in
the biomedical sciences to the study of natural flocculated SPM filling both this
spatial and dimensional gap. Fragile 3D floc samples were successfully captured
and stabilized, identifying five basic organic and inorganic floc components and
quantifying porosity and bacteria numbers. This provides new 3D floc geometric
data sets at the nanoscale that will be critical in the development of cohesive
sediment transport models. Detailed compositional and structural information
could provide novel insights into the association of pathogens and pollutants
with SPM and their impact on aquatic life.
PMID- 28692288
TI - Toward Reliable Lipoprotein Particle Predictions from NMR Spectra of Human Blood:
An Interlaboratory Ring Test.
AB - Lipoprotein profiling of human blood by 1H nuclear magnetic resonance (NMR)
spectroscopy is a rapid and promising approach to monitor health and disease
states in medicine and nutrition. However, lack of standardization of measurement
protocols has prevented the use of NMR-based lipoprotein profiling in
metastudies. In this study, a standardized NMR measurement protocol was applied
in a ring test performed across three different laboratories in Europe on plasma
and serum samples from 28 individuals. Data was evaluated in terms of (i)
spectral differences, (ii) differences in LPD predictions obtained using an
existing prediction model, and (iii) agreement of predictions with cholesterol
concentrations in high- and low-density lipoproteins (HDL and LDL) particles
measured by standardized clinical assays. ANOVA-simultaneous component analysis
(ASCA) of the ring test spectral ensemble that contains methylene and methyl
peaks (1.4-0.6 ppm) showed that 97.99% of the variance in the data is related to
subject, 1.62% to sample type (serum or plasma), and 0.39% to laboratory. This
interlaboratory variation is in fact smaller than the maximum acceptable
intralaboratory variation on quality control samples. It is also shown that the
reproducibility between laboratories is good enough for the LPD predictions to be
exchangeable when the standardized NMR measurement protocol is followed. With the
successful implementation of this protocol, which results in reproducible
prediction of lipoprotein distributions across laboratories, a step is taken
toward bringing NMR more into scope of prognostic and diagnostic biomarkers,
reducing the need for less efficient methods such as ultracentrifugation or high
performance liquid chromatography (HPLC).
PMID- 28692289
TI - Constituents of Polygala flavescens ssp. flavescens and Their Activity as
Inhibitors of Human Lactate Dehydrogenase.
AB - Four new flavonol glycosides (1-4), two oligosaccharides (5, 6), one alpha-ionone
(7), and three triterpenoid saponins (8-10), together with four known secondary
metabolites (11-14), were isolated from the aerial parts of Polygala flavescens
ssp. flavescens. All structures were elucidated on the basis of their
spectroscopic and spectrometric data. The isolates were assayed for their
inhibitory activity against isoform 5 of human lactate dehydrogenase, and
compound 11 (3,6'-di-O-sinapoylsucrose) showed an IC50 value of 90.4 MUM.
Modeling studies were carried out to suggest the putative interaction mode of
compound 11 in the enzyme active site.
PMID- 28692290
TI - Top-Down Atmospheric Ionization Mass Spectrometry Microscopy Combined With
Proteogenomics.
AB - Mass spectrometry-based protein analysis has become an important methodology for
proteogenomic mapping by providing evidence for the existence of proteins
predicted at the genomic level. However, screening and identification of proteins
directly on tissue samples, where histological information is preserved, remain
challenging. Here we demonstrate that the ambient ionization source, nanospray
desorption electrospray ionization (nanoDESI), interfaced with light microscopy
allows for protein profiling directly on animal tissues at the microscopic scale.
Peptide fragments for mass spectrometry analysis were obtained directly on
ganglia of the medicinal leech (Hirudo medicinalis) without in-gel digestion. We
found that a hypothetical protein, which is predicted by the leech genome, is
highly expressed on the specialized neural cells that are uniquely found in adult
sex segmental ganglia. Via this top-down analysis, a post-translational
modification (PTM) of tyrosine sulfation to this neuropeptide was resolved. This
three-in-one platform, including mass spectrometry, microscopy, and genome
mining, provides an effective way for mappings of proteomes under the lens of a
light microscope.
PMID- 28692291
TI - Efficient Calculation of Molecular Integrals over London Atomic Orbitals.
AB - The use of London atomic orbitals (LAOs) in a nonperturbative manner enables the
determination of gauge-origin invariant energies and properties for molecular
species in arbitrarily strong magnetic fields. Central to the efficient
implementation of such calculations for molecular systems is the evaluation of
molecular integrals, particularly the electron repulsion integrals (ERIs). We
present an implementation of several different algorithms for the evaluation of
ERIs over Gaussian-type LAOs at arbitrary magnetic field strengths. The
efficiencies of generalized McMurchie-Davidson (MD), Head-Gordon-Pople (HGP), and
Rys quadrature schemes are compared. For the Rys quadrature implementation, we
avoid the use of high precision arithmetic and interpolation schemes in the
computation of the quadrature roots and weights, enabling the application of this
algorithm seamlessly to a wide range of magnetic fields. The efficiency of each
generalized algorithm is compared by numerical application, classifying the ERIs
according to their total angular momenta and evaluating their performance for
primitive and contracted basis sets. In common with zero-field integral
evaluation, no single algorithm is optimal for all angular momenta; thus, a
simple mixed scheme is put forward that selects the most efficient approach to
calculate the ERIs for each shell quartet. The mixed approach is significantly
more efficient than the exclusive use of any individual algorithm.
PMID- 28692292
TI - Discovery of Potent and Selective Inhibitors of Cdc2-Like Kinase 1 (CLK1) as a
New Class of Autophagy Inducers.
AB - Autophagy inducers represent new promising agents for the treatment of a wide
range of medical illnesses. However, safe autophagy inducers for clinical
applications are lacking. Inhibition of cdc2-like kinase 1 (CLK1) was recently
found to efficiently induce autophagy. Unfortunately, most of the known CLK1
inhibitors have unsatisfactory selectivity. Herein, we report the discovery of a
series of new CLK1 inhibitors containing the 1H-[1,2,3]triazolo[4,5-c]quinoline
scaffold. Among them, compound 25 was the most potent and selective, with an IC50
value of 2 nM against CLK1. The crystal structure of CLK1 complexed with compound
25 was solved, and the potency and kinase selectivity of compound 25 were
interpreted. Compound 25 was able to induce autophagy in in vitro assays and
displayed significant hepatoprotective effects in the acetaminophen (APAP)
induced liver injury mouse model. Collectively, due to its potency and
selectivity, compound 25 could be used as a chemical probe or agent in future
mechanism-of-action or autophagy-related disease therapy studies.
PMID- 28692293
TI - Spectroscopic Properties and Conformational Analysis of Methyl Ester of Sinapic
Acid in Various Environments.
AB - A methyl ester of sinapic acid (MESA) has recently attracted attention due to its
antioxidant action. This article presents results of a study on the spectral and
physicochemical properties of MESA, using quantum chemistry (QC), steady-state
(absorption and fluorescence), and time-resolved fluorescence techniques (TCSPC).
The pKa of the phenol group in the ground state was determined (8.6). The pKa*
values in the excited state calculated from the Forster cycle (1.9) and from
fluorescence spectra (8.5) differed significantly but the experimental data
suggested that the first was the more probable one. Quantum yields (QYs) for both
forms have been determined. The QYs were very low (0.0017 and 0.0007) for
nondissociated and dissociated forms, respectively and lifetimes were very short
<=10 ps for both forms. The differences in the probability of H-bond formation in
the ground and the excited states were estimated by the application of the SdP
polarity scale. Dipole moments in the ground state were calculated using QC. The
ratio between dipole moments in the ground and the excited state for free
molecule was obtained from Bilot-Kawski (B-K) method. Analysis of all collected
results suggests that radical route (through hydrogen atom abstraction) of
antioxidant activity of MESA is the more probable one in a water environment at
pH below 6.
PMID- 28692294
TI - Electronic and Tunneling Predissociations in the 2ppiC1Piu+/-(upsilon = 19) and
3ppiD1Piu+/-(upsilon = 4, 5) States of D2 Studied by a Combination of XUV Laser
and Velocity Map Imaging.
AB - The predissociation mechanism of D2 near the threshold for the production of the
D(2s, 2p) fragments has been studied by measuring the fragment yield spectra,
fragment velocity map images, and fragment branching ratios D(2s)/(D(2s) + D(2p))
using a combination of XUV laser and velocity map imaging. The predissociation
dynamics of the 2ppiC1Piu+/-(upsilon = 19) and 3ppiD1Piu+/-(upsilon = 4,5) states
were studied. The 2ppiC1Piu+/-(upsilon = 19) state is a bound state due to a
shallow barrier. For the R(0) transition to the 2ppiC1Piu+(upsilon = 19) state,
the experimental results suggest that the predissociation occurs via three
channels with decreasing importance: l-uncoupling with the 2psigmaB1Sigmau+
state, tunneling, and l-uncoupling with the 3psigmaB'1Sigmau+ state. For the R(1)
transition to the 2ppiC1Piu+(upsilon = 19) state, the first channel plays the
dominant role. For the Q(1) transition to the 2ppiC1Piu-(upsilon = 19) state, the
predissociation occurs via tunneling as required by symmetry. For the
predissociation of the 3ppiD1Piu+(upsilon = 4,5) states, the experimental data
confirm the earlier results indicating that the main perturbing state is
3psigmaB'1Sigmau+. The Beutler-Fano profiles and the associated spectroscopic
parameters for the various predissociations have also been obtained. The measured
Fano-parameters q for the P- and R-branches of the 3ppiD1Piu+ state are found to
have opposite signs, and their relationships are in agreement with a formula
derived from the Fano equation. Rotationally resolved Beutler-Fano profiles were
measured for the P(2) and P(3) lines.
PMID- 28692295
TI - Identification and Characterization of Von Hippel-Lindau-Recruiting Proteolysis
Targeting Chimeras (PROTACs) of TANK-Binding Kinase 1.
AB - Proteolysis targeting chimeras (PROTACs) are bifunctional molecules that recruit
an E3 ligase to a target protein to facilitate ubiquitination and subsequent
degradation of that protein. While the field of targeted degraders is still
relatively young, the potential for this modality to become a differentiated and
therapeutic reality is strong, such that both academic and pharmaceutical
institutions are now entering this interesting area of research. In this article,
we describe a broadly applicable process for identifying degrader hits based on
the serine/threonine kinase TANK-binding kinase 1 (TBK1) and have generalized the
key structural elements associated with degradation activities. Compound 3i is a
potent hit (TBK1 DC50 = 12 nM, Dmax = 96%) with excellent selectivity against a
related kinase IKKepsilon, which was further used as a chemical tool to assess
TBK1 as a target in mutant K-Ras cancer cells.
PMID- 28692296
TI - Leaching from Palladium Nanoparticles in an Ionic Liquid Leads to the Formation
of Ionic Monometallic Species.
AB - Molecular dynamics simulations and DFT calculations suggest that leaching of
palladium species from Pd nanoparticles in ionic liquids does not involve "naked"
Pd(0) atoms or neutral ArPdX species formed by oxidative addition of arylhalides.
Instead, the ionic liquid contributes largely to leaching of ionic PdX- or PdAr+
species.
PMID- 28692298
TI - Direct Catalytic Asymmetric Aldol Addition of an alpha-CF3 Amide to Arylglyoxal
Hydrates.
AB - Direct asymmetric aldol addition of an alpha-CF3 amide to arylglyoxal hydrates
was promoted by a chiral catalyst comprising a soft Lewis acidic Cu(I), a chiral
bisphosphine ligand, and DBU. The 7-azaindoline moiety of the amide facilitates
its enolization and stabilizes the thus-generated Cu enolate, furnishing
enantioenriched aldol adducts.
PMID- 28692297
TI - Enantioselective Synthesis and in Vivo Evaluation of Regioisomeric Analogues of
the Antimalarial Arterolane.
AB - We describe the first systematic study of antimalarial 1,2,4-trioxolanes bearing
a substitution pattern regioisomeric to that of arterolane. Conformational
analysis suggested that trans-3"-substituted trioxolanes would exhibit Fe(II)
reactivity and antiparasitic activity similar to that achieved with canonical cis
4" substitution. The chiral 3" analogues were prepared as single stereoisomers
and evaluated alongside their 4" congeners against cultured malaria parasites and
in a murine malaria model. As predicted, the trans-3" analogues exhibited in
vitro antiplasmodial activity remarkably similar to that of their cis-4"
comparators. In contrast, efficacy in the Plasmodium berghei mouse model differed
dramatically for some of the congeneric pairs. The best of the novel 3" analogues
(e.g., 12i) outperformed arterolane itself, producing cures in mice after a
single oral exposure. Overall, this study suggests new avenues for modulating
Fe(II) reactivity and the pharmacokinetic and pharmacodynamic properties of 1,2,4
trioxolane antimalarials.
PMID- 28692299
TI - Nonequilibrium Synthesis of TiO2 Nanoparticle "Building Blocks" for Crystal
Growth by Sequential Attachment in Pulsed Laser Deposition.
AB - Nonequilibrium growth pathways for crystalline nanostructures with metastable
phases are demonstrated through the gas-phase formation, attachment, and
crystallization of ultrasmall amorphous nanoparticles as building blocks in
pulsed laser deposition (PLD). Temporally and spatially resolved gated
intensified charge couple device (ICCD) imaging and ion probe measurements are
employed as in situ diagnostics to understand and control the plume expansion
conditions for the synthesis of nearly pure fluxes of ultrasmall (~3 nm)
amorphous TiO2 nanoparticles in background gases and their selective delivery to
substrates. These amorphous nanoparticles assemble into loose, mesoporous
assemblies on substrates at room temperature but dynamically crystallize by
sequential particle attachment at higher substrate temperatures to grow
nanostructures with different phases and morphologies. Molecular dynamics
calculations are used to simulate and understand the crystallization dynamics.
This work demonstrates that nonequilibrium crystallization by particle attachment
of metastable ultrasmall nanoscale "building blocks" provides a versatile
approach for exploring and controlling the growth of nanoarchitectures with
desirable crystalline phases and morphologies.
PMID- 28692300
TI - Selected Mutations Revealed Intermediates and Key Precursors in the Biosynthesis
of Polyketide-Terpenoid Hybrid Sesquiterpenyl Epoxy-cyclohexenoids.
AB - Sesquiterpenyl epoxy-cyclohexenoids (SECs) show impressive biological activities.
However, the key pathways for SECs still remain unambiguous. Unexpectedly, 11 new
SECs and derivatives with diverse oxidation patterns were isolated after the
deletion of gene 274. A high accumulation of toluquinol and its new glycosides in
mutant Delta276 and further isolation of the most crucial precursors farnesyl
hydroquinone, farnesyl quinone, and three new derivatives from mutant Delta278
confirm that farnesylation at toluquinol is the key step for SECs.
PMID- 28692302
TI - Reply to Gilbert et al.: The Impact of the ASAP Trial: Maybe We Shouldn't Act So
Quickly.
PMID- 28692301
TI - High-Dose Vitamin D3 during Tuberculosis Treatment in Mongolia. A Randomized
Controlled Trial.
AB - RATIONALE: Existing trials of adjunctive vitamin D in the treatment of pulmonary
tuberculosis (PTB) are variously limited by small sample sizes, inadequate dosing
regimens, and high baseline vitamin D status among participants. Comprehensive
analyses of the effects of genetic variation in the vitamin D pathway on response
to vitamin D supplementation are lacking. OBJECTIVES: To determine the effect of
high-dose vitamin D3 on response to antimicrobial therapy for PTB and to evaluate
the influence of single-nucleotide polymorphisms (SNPs) in vitamin D pathway
genes on response to adjunctive vitamin D3. METHODS: We conducted a clinical
trial in 390 adults with PTB in Ulaanbaatar, Mongolia, who were randomized to
receive four biweekly doses of 3.5 mg (140,000 IU) vitamin D3 (n = 190) or
placebo (n = 200) during intensive-phase antituberculosis treatment. MEASUREMENTS
AND MAIN RESULTS: The intervention elevated 8-week serum 25-hydroxyvitamin D
concentrations (154.5 nmol/L vs. 15.2 nmol/L in active vs. placebo arms,
respectively; 95% confidence interval for difference, 125.9-154.7 nmol/L; P <
0.001) but did not influence time to sputum culture conversion overall (adjusted
hazard ratio, 1.09; 95% confidence interval, 0.86-1.36; P = 0.48). Adjunctive
vitamin D3 accelerated sputum culture conversion in patients with one or more
minor alleles for SNPs in genes encoding the vitamin D receptor (rs4334089,
rs11568820) and 25-hydroxyvitamin D 1alpha-hydroxylase (CYP27B1: rs4646536)
(adjusted hazard ratio >= 1.47; P for interaction <= 0.02). CONCLUSIONS: Vitamin
D3 did not influence time to sputum culture conversion in the study population
overall. Effects of the intervention were modified by SNPs in VDR and CYP27B1.
Clinical trial registered with www.clinicaltrials.gov (NCT01657656).
PMID- 28692303
TI - Searching for Biosignatures in Exoplanetary Impact Ejecta.
AB - With the number of confirmed rocky exoplanets increasing steadily, their
characterization and the search for exoplanetary biospheres are becoming
increasingly urgent issues in astrobiology. To date, most efforts have
concentrated on the study of exoplanetary atmospheres. Instead, we aim to
investigate the possibility of characterizing an exoplanet (in terms of
habitability, geology, presence of life, etc.) by studying material ejected from
the surface during an impact event. For a number of impact scenarios, we estimate
the escaping mass and assess its subsequent collisional evolution in a
circumstellar orbit, assuming a Sun-like host star. We calculate the fractional
luminosity of the dust as a function of time after the impact event and study its
detectability with current and future instrumentation. We consider the
possibility to constrain the dust composition, giving information on the geology
or the presence of a biosphere. As examples, we investigate whether calcite,
silica, or ejected microorganisms could be detected. For a 20 km diameter
impactor, we find that the dust mass escaping the exoplanet is roughly comparable
to the zodiacal dust, depending on the exoplanet's size. The collisional
evolution is best modeled by considering two independent dust populations, a
spalled population consisting of nonmelted ejecta evolving on timescales of
millions of years, and dust recondensed from melt or vapor evolving on much
shorter timescales. While the presence of dust can potentially be inferred with
current telescopes, studying its composition requires advanced instrumentation
not yet available. The direct detection of biological matter turns out to be
extremely challenging. Despite considerable difficulties (small dust masses,
noise such as exozodiacal dust, etc.), studying dusty material ejected from an
exoplanetary surface might become an interesting complement to atmospheric
studies in the future. Key Words: Biosignatures-Exoplanets-Impacts-Interplanetary
dust-Remote sensing. Astrobiology 17, 721-746.
PMID- 28692304
TI - A combination method based on chitosan adsorption and duckweed (Lemna gibba L.)
phytoremediation for boron (B) removal from drinking water.
AB - The metalloid boron (B) and its compounds widely exist in the environment, and
boron can have hazardous effects on plants, animals, and human beings when it is
found in high concentrations in water bodies. It is difficult and costly to
remove B with conventional treatment methods from drinking water. Therefore,
alternative and cost-effective treatment techniques are necessary. In this study,
for the first time, a novel and environmentally friendly method based on the
phytoremediation ability of chitosan and duckweed (Lemna gibba L.) combination
was evaluated for B removal from drinking water. Our results from batch
adsorption experiment indicated that the highest B uptake capacity of chitosan
bead was found as 3.18 mg/g, and we determined the optimal B sorption occurs at
pH value of 7. The Langmuir isotherm and pseudo-second-order kinetic model better
fitted the equilibrium obtained for B removal. B in drinking water could be
reduced to less than 2.4 mg L -1 when 0.05 g of plant-based chitosan beads and 12
L. gibba fronds were used in the 4-day treatment period.
PMID- 28692305
TI - Fight fire with fire: Gene therapy strategies to cure HIV.
AB - INTRODUCTION: Human Immunodeficiency Virus (HIV) to date remains one of the most
notorious viruses mankind has ever faced. Despite enormous investments in HIV
research for more than 30 years an effective cure for HIV has been elusive. Areas
covered: Combination antiretroviral therapy (cART) suppresses active viral
replication, but is not able to eliminate the virus completely due to stable
integration of HIV inside the host genome of infected cells and the establishment
of a latent reservoir, that is insensitive to cART. Nevertheless, this latent HIV
reservoir is fully capable to refuel viral replication when treatment is stopped,
creating a major obstacle towards a cure for HIV. Several gene therapy approaches
ranging from the generation of HIV resistant CD4 + T cells to the eradication of
HIV infected cells by immune cell engineering are currently under pre-clinical
and clinical investigation and may present a promising road to a cure. In this
review, we focus on the status and the prospects of gene therapy strategies to
cure/eradicate HIV. Expert commentary: Recent advances in gene therapy for
oncology and infectious diseases indicate that gene therapy may be a feasible and
very potent cure strategy, and therefore a potential game changer in the search
for an effective HIV cure.
PMID- 28692306
TI - Development and validation of an electrochemiluminescent ELISA for quantitation
of oral insulin tregopil in diabetes mellitus serum.
AB - AIM: Tregopil, a novel PEGylated human insulin is in clinical development for
oral delivery in diabetes treatment. The aim of the study was to develop and
validate a sensitive and specific ELISA method for quantitating Tregopil in
diabetes subjects on basal Glargine, since most commercially available insulin
kits either do not detect Tregopil or show significant reactivity to Glargine.
METHODS: An electrochemiluminescent ELISA was developed and validated for
Tregopil quantitation in diabetes serum. RESULTS: The method has a LLOQ of 0.25
ng/ml, shows minimum cross-reactivity to Glargine and was successfully tested
using a subset of samples from Tregopil-dosed Type 1 diabetes mellitus patients.
CONCLUSION: The ELISA method is sensitive and can be used to support accurate
measurement of Tregopil with no cross-reactivity to Glargine and its metabolites
in clinical studies.
PMID- 28692307
TI - Association of the -344T/C polymorphism in aldosterone synthase gene promoter
with left ventricular structure in Chinese Han: A meta-analysis.
AB - No consensus view has been published on the relationship between the aldosterone
synthase gene (CYP11B2) -344C/T polymorphism and left ventricular hypertrophy
(LVH) in Chinese Han. We undertook a meta-analysis to investigate the potential
association of this polymorphism and left ventricular structure-related
phenotypes, including left ventricular mass (LVM), left ventricular mass index
(LVMI), left ventricular end systolic diameter (LVESD), left ventricular end
diastolic dimension (LVEDD), left ventricular posterior wall thickness (LVPWT),
and interventricular septal wall thickness (IVS). Studies in English and Chinese
were found based on a systematic search of Medline, Embase, CNKI, and Wanfang
databases. The dominant model (TT vs. TC+CC) and homozygote model (TT vs. CC)
were selected to examine the association between the -344C/T polymorphism and
LVH. The random-effects model was used to pool data. From a total of 3104
participants, despite the investigation of six echocardiographic indicators, we
found no significant association between the -344C/T variant and LVH in the whole
group and the subgroup analyses by blood pressure. However, in the subgroup of
northern Han Chinese, TT genotype had higher LVPWT than CC genotype and TC
genotype (pheterogeneity = 0.4, pvalue = 0.04, 95% CI 0.09 (0.00, 0.18)). In
addition, no evidence of publication bias was observed. In conclusion, our meta
analysis indicated that subjects with TT genotype might have higher risk of
developing LVH in northern Han Chinese.
PMID- 28692308
TI - LC-MS determination of triazolam and its hydroxy metabolites in mouse dried blood
spots: application to transgenic mouse pharmacokinetic studies.
AB - AIM: The objective of this study was to develop a LC-MS/MS method for the
simultaneous determination of triazolam (TRZ) and its two hydroxy metabolites in
transgenic mouse dried blood spots (DBS) using BALB/c mouse blood as a surrogate
biomatrix. METHODOLOGY/RESULTS: The DBS method involved spotting volume of 10 MUl
using Ahlstrom 226 sample collection cards. A 'whole spot' analysis (6-mm punch)
involved extraction of analytes using water and acetonitrile containing an
internal standard. DBS samples were analyzed by a validated LC-MS/MS method with
a run time of 4 min. CONCLUSION: This validated LC-MS/MS method using DBS
extraction was applied to quantitation of TRZ, alpha-hydroxytriazolam and 4
hydroxytriazolam in a CYP3A4 transgenic mouse oral pharmacokinetic study of TRZ.
PMID- 28692309
TI - Development and validation of a LC-MS/MS method for the quantification of the
checkpoint kinase 1 inhibitor SRA737 in human plasma.
AB - AIM: SRA737 is an orally active small-molecule inhibitor of checkpoint kinase 1
being investigated in an oncology setting. A HPLC-MS/MS method for quantifying
plasma concentrations of SRA737 was validated. METHODS & RESULTS: Sample
preparation involved protein precipitation with acetonitrile following addition
of 13C15N-deuterated SRA737 as internal standard. A rapid and selective method
was fully validated across a range of 5-20,000 ng/ml, exhibiting good
sensitivity, overall precision (expressed as coefficient of variation) <=8.0% and
accuracy 96-102%. Consistently high recovery was observed, with no matrix effect
and a lower limit of quantitation of 5 ng/ml. CONCLUSION: A novel method for
analyzing SRA737 in human plasma has been validated and is now being utilized for
quantification of SRA737 in a Phase I trial.
PMID- 28692310
TI - Role of MicroRNAs in shaping innate immunity and as therapeutic targets for
autoimmune diseases.
PMID- 28692311
TI - Prospective direct comparison of antihypertensive effect and safety between high
dose amlodipine or indapamide in hypertensive patients uncontrolled by standard
doses of angiotensin receptor blockers and amlodipine.
AB - OBJECTIVE: When hypertension is uncontrolled by routine treatment with an
angiotensin II receptor blocker (ARB) and the calcium channel blocker amlodipine
(5 mg), the dose of amlodipine can be increased or a diuretic can be added. We
investigated the more effective option in a prospective multicenter open-label
study. METHODS: Hypertensive patients were recruited if the target blood pressure
(BP) in The Japanese Society of Hypertension 2009 guideline could not be achieved
with standard-dose ARB therapy and amlodipine (5 mg). PATIENTS: Patients were
divided into three groups. Group-1 was switched to a combination of irbesartan
(100 mg) and amlodipine (10 mg). Group-2A was changed to a combination of
irbesartan (100 mg), amlodipine (5 mg), and indapamide, while Group-2B received a
standard-dose ARB and amlodipine (5 mg) plus indapamide. Patients were assigned
by their attending physicians and were followed for 6 months. The primary
endpoint was the antihypertensive effect of each regimen. RESULTS: Group-1
contained 85 patients, Group-2A had 49 patients, and Group-2B had 4 patients. We
only analyzed Group-1 and Group-2A due to the small size of Group-2B. In both
groups, systolic BP and diastolic BP were significantly decreased up to 6 months
(all p < 0.001). Reduction of systolic BP was greater in Group-1 than Group-2A
after 1 month and 6 months (both p < 0.05). Uric acid was increased in Group-2A
after 3 months, but not at 6 months. CONCLUSION: Although both regimens were
effective for reducing BP, increasing amlodipine to 10 mg daily controlled
hypertension without elevation of serum uric acid.
PMID- 28692313
TI - Prehypertension and socioeconomic status: A cross-sectional study in Chongqing,
China.
AB - BACKGROUND: A large amount of research is available on the relationship between
socioeconomic status (SES) and hypertension. However, the relationship between
SES and prehypertension remains complex and unclear. Prehypertension is defined
as a systolic blood pressure (SBP) between 120 and 139 mmHg or diastolic blood
pressure (DBP) 80 and 89 mmHg. This paper focuses on the impact of SES on the
prevalence of prehypertension and provides suggestions for the prevention and
control measures of prehypertension and health resource allocation. METHOD: Using
multistage random sampling, 11,773 subjects were selected. Subjects aged above 15
years old and subjects who had been living in the eight selected districts for
more than 6 months were analyzed using a multivariable logistical model. RESULTS:
The prevalence of prehypertension at the present time reaches 55.17%, with it
being higher among men than that among women (63.15% vs. 47.19%, p < 0.05). After
adjustment for other factors such as age and gender, a logistic regression showed
that a higher education level and a history of marital status were significantly
associated with prehypertension. CONCLUSIONS: People of different SES indicate
different working and living conditions. They also face different risk factors
for prehypertension. Lower education and a history of marital status were
associated with a higher risk of prehypertension among residents in Chongqing,
China.
PMID- 28692314
TI - Long Term Low Molecular Weight Heparin Anticoagulant Therapy Modulates Thrombin
Generation and D-dimer in Patients with Cancer and Venous Thromboembolism.
AB - We enrolled 62 consecutive patients with advanced stage cancers and venous
thromboembolism (VTE), prospectively followed until 1 year. All patients received
6 month low-molecular-weight heparin (LMWH) therapy. We evaluated thrombin
generation (TG) and D-dimer levels at different time points, to determine whether
they were sensitive to LMWH and explore a possible association with VTE
recurrence, bleeding, and overall survival. During LMWH, levels of TG and D-dimer
significantly dropped. No VTE recurrences occurred, one patient had cancer
related intestinal hemorrhage. LMWH treatment was effective in controlling
patient hypercoagulation. No VTE recurrences were detected. High D-dimer
concentration was an independent predictor of poor survival.
PMID- 28692315
TI - Biodegradable nanoparticles for improved kidney bioavailability of rhein:
preparation, characterization, plasma, and kidney pharmacokinetics.
AB - The aim of this work is to develop biodegradable nanoparticles for improved
kidney bioavailability of rhein (RH). RH-loaded nanoparticles were prepared using
an emulsification solvent evaporation method and fully characterized by several
techniques. Kidney pharmacokinetics was assessed by implanting a microdialysis
probe in rat's kidney cortex. Blood samples were simultaneously collected (via
femoral artery) for assessing plasma pharmacokinetics. Optimized nanoparticles
were small, with a mean particle size of 132.6 +/- 5.95 nm, and homogeneously
dispersed. The charge on the particles was nearly zero, the encapsulation
efficiency was 62.71 +/- 3.02%, and the drug loading was 1.56 +/- 0.15%. In vitro
release of RH from the nanoparticles showed an initial burst release followed by
a sustained release. Plasma and kidney pharmacokinetics showed that encapsulation
of RH into nanoparticles significantly increased its kidney bioavailability
(AUCkidney/AUCplasma = 0.586 +/- 0.072), clearly indicating that nanoparticles
are a promising strategy for kidney drug delivery.
PMID- 28692317
TI - Using Delayed Toxicities to Re-evaluate Tolerability in Phase 2 Trials: A Case
Example using Bortezomib.
AB - In advanced stage patients enrolled in dose-finding trials, it is difficult to
assess delayed toxicities because frequently patients discontinue after one or
two cycles of treatment. Patients enrolled in phase 2 trials are typically
followed longer to assess efficacy. Thus, their data may be useful for evaluating
long-term tolerability. We illustrate this using as example two phase 2
bortezomib trials (total N = 172) conducted by SWOG. While treatment-related
severe toxicity rates based on cycle 1 were acceptable (23% and 31%), they were
notably higher over extended administration (37% and 70%). This additional
information should be considered when designing subsequent trials.
PMID- 28692316
TI - H7N9 avian influenza A virus in China: a short report on its circulation, drug
resistant mutants and novel antiviral drugs.
AB - INTRODUCTION: The first human H7N9 avian influenza virus case was reported in
Shanghai in 2013. Shortly thereafter, this virus spread to other regions in
China. Molecular analysis indicated that the H7N9 virus is a reassortant virus
containing internal genes from the H9N2 virus and previously described mammalian
adaption markers, which could allow the virus to adapt efficiently to a mammalian
host. Fortunately, there is no evidence of sustained person-to-person spread.
Most of the human H7N9 cases have a history of exposure to live poultry markets
(LPMs). The circulating H7N9 were low pathogenic viruses, however highly
pathogenic H7N9 viruses were recently identified in human cases. Areas covered:
In the present article, the circulation of H7N9 in LPMs of China, the five waves
of H7N9 infection in humans, recently identified drug resistant mutants and
potential antiviral drugs against H7N9 are discussed; this may provide further
understanding of the evolution and pandemic potential of the H7N9 influenza
viruses. Expert commentary: All the data reveal that the major source of H7N9
viruses are LPMs and the H7N9 virus is still circulating widely in China. It is
concerning that the recent emergence of highly pathogenic H7N9 viruses may result
in highly transmissible viruses in mammalian species.
PMID- 28692318
TI - Misconceptions and Malpractices Toward Antibiotic Use in Childhood Upper
Respiratory Tract Infections Among a Cohort of Lebanese Parents.
AB - Antimicrobial resistance is an emerging global health threat. Misuse and abuse of
antibiotics are of particular concern in the pediatric population. Since
management of childhood illnesses depends considerably on parents' perceptions,
the objectives of this study were to report parents' perspectives and assess
their practices toward antibiotics used for upper respiratory tract infections
(URTIs) in children. Using a cross-sectional design, anonymous structured
questionnaires were completed by 1,037 parents in public and private schools
across Lebanon's largest governorate. Descriptive statistics were used to report
participants' responses. A multivariate analysis was performed to identify
factors affecting knowledge and malpractice related to antibiotic use.
Significant misconceptions and malpractices were identified among parents. For
instance, 33.9% of parents considered that antibiotics are helpful in treating
common cold among children and 36.2% believed antibiotics expedite the recovery
of their child with common cold infection. Moreover, there was a lack of
knowledge concerning antibiotic coverage, since 37.9% of the respondents believed
that antibiotics treat viral infections and 21.5% were neutral toward this
question. Around 20% of the participants believed they can reduce the dose of
antibiotics if the child gets better. Significant factors associated with poor
knowledge and misuses were parents' lower educational and socioeconomic levels.
Despite extensive evidence on the limited role of antibiotics in URTIs, parents
in Lebanon continue to misuse them. More concerted efforts are needed to improve
parents' knowledge and practices with regard to the rational use of antibiotics.
PMID- 28692319
TI - Low energy X-ray (grenz ray) treatment of purified islets prior to allotransplant
markedly decreases passenger leukocyte populations.
AB - Grenz rays, or minimally penetrating X-rays, are known to be an effective
treatment of certain recalcitrant immune-mediated skin diseases, but their use in
modulating allograft rejection has not been tested. We examined the capacity of
grenz ray treatment to minimize islet immunogenicity and extend allograft
survival in a mouse model. In a preliminary experiment, 1 of 3 immunologically
intact animals demonstrated long-term acceptance of their grenz ray treated islet
allograft. Further experiments revealed that 28.6% (2 of 7) grenz ray treated
islet allografts survived >60 d. A low dose of 20Gy, was important; a 4-fold
increase in radiation resulted in rapid graft failure, and transplanting a higher
islet mass did not alter this outcome. To determine whether increased islet
allograft survival after grenz treatment would be masked by immunosuppression, we
treated the recipients with CTLA-4 Ig, and found an additive effect, whereby
17.5% more animals accepted the graft long-term versus those with CTLA-4 Ig
alone. Cell viability assays verified that islet integrity was maintained after
treatment with 20Gy. As well, through splenocyte infiltration analysis, donor
CD4+ T cell populations 24-hours after transplant were decreased by more than16
fold in recipients receiving irradiated islets compared with control. Donor CD8+
T cell populations, although less prevalent, decreased in all treatment groups
compared with control. Our results suggest that brief treatment of isolated
islets with low energy grenz rays before allotransplantation can significantly
reduce passenger leukocytes and promote graft survival, possibly by inducing
donor dendritic cells to differentiate toward a tolerogenic phenotype.
PMID- 28692320
TI - The Probiotic VSL#3 Modulates Colonic Macrophages, Inflammation, and Microflora
in Acute Trinitrobenzene Sulfonic Acid Colitis.
AB - The probiotic mixture VSL#3 attenuates colitis in patients with Inflammatory
Bowel Disease (IBD) and in animal models of this condition, but the mechanisms
involved are incompletely understood. VSL#3 alters macrophage morphology and
secretory profile in vitro in a polarization-dependent manner. We examined the
effect of VSL#3 on macrophages in acute trinitrobenzene sulfonic acid-induced
colitis. Rats were randomized to normal, colitis, or colitis+VSL#3 groups. After
sacrifice, the colons were evaluated for macroscopic and microscopic damage.
Serum cytokine levels were measured, and microbiome analysis undertaken. Total
and M1 colonic macrophages, and total and proliferating hepatic macrophages were
assessed by double immunofluorescence staining. Colitis+VSL#3 rats had lower
macroscopic damage, with less microscopic damage in the proximal colon, compared
with colitis alone. Colitis significantly increased colonic macrophage
infiltration, which was significantly reduced by VSL#3 treatment. VSL#3 did not
decrease the colitis-induced surge of colonic M1 macrophages or hepatic
macrophages. VSL#3 reduced colitis-induced serum cytokine levels, and induced
restoration of colonic transcript levels for pro-inflammatory, anti-inflammatory,
and barrier proteins to, or past, normal levels. Fecal bacteria distribution
changed between groups. In summary, the probiotic VSL#3 reduces colitis severity,
colonic macrophage infiltration, and serum cytokine levels, but does not dampen
the pro-inflammatory phenotype of M1 macrophages.
PMID- 28692321
TI - A systematic literature review of cysteamine bitartrate in the treatment of
nephropathic cystinosis.
AB - OBJECTIVES: To summarize available clinical evidence for cysteamine bitartrate
preparations in the treatment of nephropathic cystinosis as identified through a
systematic literature review (SLR). METHODS: We searched MEDLINE, MEDLINE In
Process and Embase using Ovid with a predefined search strategy through 19
January 2016. All publicly available clinical reports on the use of delayed
release (DR) cysteamine bitartrate (Procysbi 1 ) or immediate-release (IR)
cysteamine bitartrate (Cystagon 2 ) in patients with cystinosis were included.
RESULTS: We identified a total of 103 publications and 10 trial records. Of
these, 9 studies describe DR cysteamine bitartrate (n = 267 patients), 42
describe IR cysteamine bitartrate (n = 1,427 patients) and in 53 studies the
exact preparation was not specified (n = 906 patients). The vast majority of the
studies used a non-randomized study design, with randomized clinical trials
(RCTs) being scarce (1 study comparing DR and IR formulation) and case reports (n
= 49) being the most common study design representing 47% of the total.
CONCLUSION: A substantial evidence base for cysteamine bitartrate in the
treatment of nephropathic cystinosis was identified. However, the majority of the
evidence was of relatively low quality, with evidence levels of 3 or 4.
PMID- 28692322
TI - The use of lasers in the treatment of skin cancer: A review.
AB - BACKGROUND: In considering skin cancer, a number of factors-including
effectiveness, simplicity of treatment, cost, and esthetic outcomes-are important
to ensure patient's satisfaction. There are several existing interventions, such
as electrodessication and curettage, excision, Mohs surgery, radiation therapy,
cryotherapy, and topical/oral treatments. Laser therapy has emerged as a new
promising alternative that should be explored. OBJECTIVE: To review the
literature on the dermatological use of laser therapy in the treatment of skin
cancer. RESULTS: A review of articles available on the MEDLINE and Web of Science
databases until May 2017 yielded 24 and 6 studies, respectively, on laser therapy
in the treatment of skin cancers, particularly melanoma, basal cell carcinoma,
and squamous cell carcinoma. The four laser subtypes included solid-state, diode,
dye, and gas lasers. CONCLUSION: Review of the literature demonstrates the
progress of dermatological understanding of the clinical implications of laser
therapy in the treatment of premalignant and malignant neoplasms of the skin, and
suggests that this treatment modality might be a viable option for some patients.
PMID- 28692324
TI - Effect of Goat's Milk Supplementation with Tamr on Free Fatty Acids, Antioxidant
Activity, and Probiotic Bacteria of Bio-Rayeb Milk.
AB - Tamr (dried dates) has a high sugar content, essential vitamins, and high
nutrient density. Dairy products still are the most typical carriers of probiotic
bacteria. Six treatments of bio-rayeb milk were manufactured from goat's milk
fortified with 5%, 10%, 15%, 20%, and 25% Tamr using ABT-5 culture. Rayeb milk
containing tamr had lower pH and fat and higher carbohydrate, total solids,
dietary fiber, ash, total protein, water-soluble nitrogen, and total volatile
fatty acids. Mixing tamr with bio-rayeb milk increased nutritional value by
decreasing saturated fatty acids and increasing unsaturated fatty acids, oleic,
linoleic, alpha-linolenic acids, and antioxidant activity values. The greatest
counts of probiotic bacteria (L. acidophilus and Bifidobacterium) were detected
in tamr rayeb milk, which increased the healthy value. The recommended level of
bifidobacteria as a probiotic (107 cfu g-1) was exceeded for treatments of tamr
rayeb milk and remained above 107 cfu g-1 until the end of storage. Adding 10% or
15% tamr to goat's milk highly improved the sensory properties of rayeb milk.
PMID- 28692323
TI - Identifying Inhibitors of Inflammation: A Novel High-Throughput MALDI-TOF
Screening Assay for Salt-Inducible Kinases (SIKs).
AB - Matrix-assisted laser desorption/ionization time-of-flight (MALDI TOF) mass
spectrometry has become a promising alternative for high-throughput drug
discovery as new instruments offer high speed, flexibility and sensitivity, and
the ability to measure physiological substrates label free. Here we developed and
applied high-throughput MALDI TOF mass spectrometry to identify inhibitors of the
salt-inducible kinase (SIK) family, which are interesting drug targets in the
field of inflammatory disease as they control production of the anti-inflammatory
cytokine interleukin-10 (IL-10) in macrophages. Using peptide substrates in in
vitro kinase assays, we can show that hit identification of the MALDI TOF kinase
assay correlates with indirect ADP-Hunter kinase assays. Moreover, we can show
that both techniques generate comparable IC50 data for a number of hit compounds
and known inhibitors of SIK kinases. We further take these inhibitors to a
fluorescence-based cellular assay using the SIK activity-dependent translocation
of CRTC3 into the nucleus, thereby providing a complete assay pipeline for the
identification of SIK kinase inhibitors in vitro and in cells. Our data
demonstrate that MALDI TOF mass spectrometry is fully applicable to high
throughput kinase screening, providing label-free data comparable to that of
current high-throughput fluorescence assays.
PMID- 28692325
TI - Reliability of the gross motor function classification system and the manual
ability classification system in children with cerebral palsy in Tanzania.
AB - OBJECTIVES: Gross Motor Function Classification System (GMFCS) and Manual Ability
Classification System (MACS) are broadly studied in high-income countries, but
data concerning their functioning are lacking in developing countries. Therefore,
we analyzed their reliability and sensitivity to change in children with cerebral
palsy in Tanzania. METHODS: GMFCS and MACS are two ordinal grading systems used
to assess motor functions while observing children's performances. Forty-nine
children were classified by two independent physiotherapy students at baseline,
after one month and after one year. Reliability and sensitivity to change were
analyzed using intraclass correlation coefficient (ICC), effect size (ES),
standard response mean (SRM), standard error of measurement (SEM), and minimal
detectable change (MDC). RESULTS: Inter- (ICC = 0.97/0.95 for GMFCS/MACS) and
intra-rater reliability (ICC = 0.98/0.96 GMFCS/MACS) were excellent. Sensitivity
to change was small (ES = -0.14/0.11, SRM = -0.24;/0.24 GMFCS/MACS). SEM was 0.2
points, resulting in MDC = 0.5/0.7 for GMFCS/MACS, respectively. CONCLUSIONS:
GMFCS and MACS demonstrated excellent reliability, but not sensitivity to change.
PMID- 28692326
TI - Deletion of eIF2beta lysine stretches creates a dominant negative that affects
the translation and proliferation in human cell line: A tool for arresting the
cell growth.
AB - BACKGROUND: Eukaryote initiation factor 2 subunit beta (eIF2beta) plays a crucial
role in regulation protein synthesis, which mediates the interaction of eIF2 with
mRNA. eIF2beta contains evolutionarily conserved polylysine stretches in amino
terminal region and a zinc finger motif in the carboxy-terminus. METHODS: The
gene eIF2beta was cloned under tetracycline transcription control and the
polylysine stretches were deleted by site-directed mutagenesis (eIF2betaDelta3K).
The plasmid was transfected into HEK 293 TetR cells. These cells were analyzed
for their proliferative and translation capacities as well as cell death rate.
Experiments were performed using gene reporter assays, western blotting, flow
cytometry, cell sorting, cell proliferation assays and confocal
immunofluorescence. RESULTS: eIF2betaDelta3K affected negatively the protein
synthesis, cell proliferation and cell survival causing G2 cell cycle arrest and
increased cell death, acting in a negative dominant manner against the native
protein. Polylysine stretches are also essential for eIF2beta translocated from
the cytoplasm to the nucleus, accumulating in the nucleolus and eIF2betaDelta3K
did not make this translocation. DISCUSSION: eIF2beta is involved in the protein
synthesis process and should act in nuclear processes as well. eIF2betaDelta3K
reduces cell proliferation and causes cell death. Since translation control is
essential for normal cell function and survival, the development of drugs or
molecules that inhibit translation has become of great interest in the scenario
of proliferative disorders. In conclusion, our results suggest the dominant
negative eIF2betaDelta3K as a therapeutic strategy for the treatment of
proliferative disorders and that eIF2beta polylysine stretch domains are
promising targets for this.
PMID- 28692327
TI - Fluorescence of Picrosirius Red Multiplexed With Immunohistochemistry for the
Quantitative Assessment of Collagen in Tissue Sections.
AB - The low cost and simplicity of picrosirius red (PSR) staining have driven its
popularity for collagen detection in tissue sections. We extended the versatility
of this method by using fluorescent imaging to detect the PSR signal and applying
automated quantification tools. We also developed the first PSR protocol that is
fully compatible with multiplex immunostaining, making it possible to test
whether collagen structure differs across immunohistochemically labeled regions
of the tissue landscape. We compared our imaging method with two gold standards
in collagen imaging, linear polarized light microscopy and second harmonic
generation imaging, and found that it is at least as sensitive and robust to
changes in sample orientation. As proof of principle, we used a genetic approach
to overexpress beta catenin in a patchy subset of mouse prostate epithelial cells
distinguished only by immunolabeling. We showed that collagen fiber length is
significantly greater near beta catenin overexpressing cells than near control
cells. Our fluorescent PSR imaging method is sensitive, reproducible, and offers
a new way to guide region of interest selection for quantifying collagen in
tissue sections.
PMID- 28692328
TI - Fabs-in-tandem immunoglobulin is a novel and versatile bispecific design for
engaging multiple therapeutic targets.
AB - In recent years, the development of bispecific antibody (bsAb) has become a major
trend in the biopharmaceutical industry. By simultaneously engaging 2 molcular
targets, bsAbs show unique mechanisms of action that could lead to clinical
benefits unattainable by conventional monoclonal antibodies. Various bsAb
generation formats have been described, and several are being investigated in
clinical development. However, some bsAb constructs have proven to be problematic
due to their unfavorable physicochemical and pharmacokinetic properties, as well
as poor manufacturing efficiencies. We describe here a new bispecific design,
Fabs-in-tandem immunoglobulin (FIT-Ig), in which 2 antigen-binding fragments are
fused directly in a crisscross orientation without any mutations or use of
peptide linkers. This unique design provides a symmetric IgG-like bispecific
molecule with correct association of 2 sets of VH/VL pairs. We show that FIT-Ig
molecules exhibit favorable drug-like properties, in vitro and in vivo functions,
as well as manufacturing efficiency for commercial development.
PMID- 28692329
TI - Surrogate strains of human pathogens for field release.
AB - Surrogate microorganisms, in short surrogates, are an essential part of pathogen
research. Compared to surrogates used in controlled laboratory environments,
surrogates for field release are restricted by concerns about human and
environmental safety. For field research of food-borne pathogens, strains of an
attenuated pathogen or strains of genetically close non-pathogenic species have
been used as surrogates. Genetic modification is usually performed to attenuate
virulence, through for examples deletion of genes of virulence and
transcriptional regulators and removal of virulence plasmids, and to facilitate
detection and monitoring through observing antibiotic resistance, fluorescence,
and bioluminescence. For field research of a biological warfare agent Bacillus
anthracis, strains of genetically close non-pathogenic species or strains of
genetically distant non-pathogenic species have been used, mostly without any
genetic modification. Recently, we constructed strains of Bacillus thuringiensis
as surrogates for B. anthracis, demonstrating that strain engineering could
significantly enhance the utility of surrogates, and that the application of a
simple genetic circuit could significantly impact surrogate safety. Thus far,
enormous potential of biotechnology has not been exploited enough due to safety
concerns regarding the field release of genetically engineered microorganisms.
However, synthetic biology is rapidly developing, providing new concepts for
biocontainment as well as ingenious genetic circuits and devices, which should be
applied in future research of field-use surrogates.
PMID- 28692330
TI - Regulation of cell wall genes in response to DEFECTIVE KERNEL1 (DEK1)-induced
cell wall changes.
AB - Defective Kernel1 (DEK1) is a plant-specific calpain involved in epidermis
specification and maintenance. DEK1 regulation of the epidermal cell wall is
proposed to be key to ensure tissue integrity and coordinated growth. Changes in
the expression of DEK1 are correlated with changes in the expression of cell wall
related genes. For example, we have found that Lipid transfer protein 3 (LTP3),
EXPANSIN 11 (EXP11), and an AP2 transcription factor (AP2TF) are misexpressed in
plants with constitutively altered levels of DEK1 activity. RT-qPCR studies show
that LTP3 and AP2TF may respond to a DEK1-generated signal whereas EXP11 is not
altered immediately after dexamethasone induction of CALPAIN suggesting it is not
in the direct signaling pathway downstream of DEK1. Our data suggest these genes
are regulated by a feedback mechanism in response to DEK1-induced changes in the
cell wall, and contribute to the phenotypes seen in plants with altered DEK1
expression.
PMID- 28692331
TI - Leveraging Implementation Science to Improve Cancer Care Delivery and Patient
Outcomes.
PMID- 28692332
TI - Correspondence between the results of functional analyses and brief functional
analyses.
AB - PURPOSE: This study sought to examine the correspondence between brief functional
analyses and more thorough functional analyses as described in the model of
functional assessment proposed by Vollmer et al.1 Methods: A panel of trained
clinicians indicated the presence/absence of specific functions of problem
behavior based on graphic results from brief functional analyses and functional
analyses conducted with 19 participants. These conclusions were compared across
assessments. RESULTS: The functions identified by the panel based on results of
brief functional analyses had low correspondence with those of the more thorough
functional analysis conducted with the same participants. CONCLUSIONS: Although
brief-functional analyses appear regularly in clinical practice and the
literature, findings from this study suggest that results may differ from those
of more thorough functional analyses. Additional study is necessary to determine
the cause of discrepant results between these two methodologies.
PMID- 28692333
TI - Boron and the evolutionary development of roots.
AB - Experimental work has shown that Boron (i.e., Boric acid, B) is an essential and
multifunctional microelement for vascular plant development. In addition to its
other functions, which include xylem development and lignin biosynthesis, we now
know that B is involved in phytohormone-signaling and influences the mechanical
properties of intercellular pectins. From these data, we conclude that B played
an important role during the evolutionary development of lignified tissues, and
that it may have been involved in the evolution of vascular plant roots, as
hypothesized by D. H. Lewis in 1980. Herein, we review the data pertaining to
Lewis' hypothesis, present experimental results on the role of B in root (vs.
rhizoid) formation in sunflower vs. a liverwort, and describe the appearance of
roots in the fossil record. Open questions are addressed, notably the lack of our
knowledge concerning soil microbes and their interactive roles with the
micronutrient B during root formation.
PMID- 28692334
TI - Impact of salicylic acid- and jasmonic acid-regulated defences on root
colonization by Trichoderma harzianum T-78.
AB - We recently found that the beneficial fungus Trichoderma harzianum T-78 primes
tomato plants for salicylic acid (SA)- and jasmonic acid (JA)-regulated defenses,
resulting in enhanced resistance against the root knot nematode Meloidogyne
incognita. By using SA- and JA-impaired mutant lines and exogenous hormonal
application, here we investigated whether the SA- and JA-pathways also have a
role in T-78 root colonization of Arabidopsis thaliana. Endophytic colonization
by T-78 was faster in the SA-impaired mutant sid2 than in the wild type.
Moreover, elicitation of SA-dependent defenses by SA application reduced T-78
colonization, indicating that the SA-pathway affects T-78 endophytism. In
contrast, elicitation of the JA-pathway, which antagonized SA-dependent defenses,
resulted in enhanced endophytic colonization by T-78. These findings are in line
with our previous observation that SA-dependent defenses are repressed by T-78,
which likely aids colonization by the endophytic fungus.
PMID- 28692335
TI - The coding sequence of firefly luciferase reporter gene affects specific
hyperexpression in Arabidopsis thaliana cpl1 mutant.
AB - Forward genetic screening of mutants using firefly luciferase (LUC) reporter gene
became a standard practice in plant research. Such screenings frequently
identified alleles of CPL1 (Carboxyl-terminal Phosphatase-Like 1) regardless of
promoters or pathways studied. Expression of the corresponding endogenous genes
often shows the minimal difference between wild type and cpl1. Here we show that
the LUC coding sequence is responsible for the high expression in cpl1, using a
classical RD29a-LUC. Deletion of the LUC 3'-UTR did not change hyperactivation of
LUC in cpl1. However, a codon-modified LUC (LUC2) produced similar expression
levels both in wild type and in cpl1. These results indicate that the coding
region of LUC is responsible for the cpl1-specific LUC overexpression uncoupled
with the expression of the endogenous counterpart.
PMID- 28692336
TI - Positive selection analysis highlights key positions in plant PP2A regulatory
subunits.
AB - A versatile hub for cellular control, the eukaryotic protein phosphatase 2A
(PP2A) enzyme family is thought to achieve specificity through combinatorial
complexity. Phylogenetic analysis has revealed that expansion of PP2A gene
families resulted from whole genome duplications followed by non-random gene
loss, and selection analysis suggests that retention of B56/PPP2R5 gene family
members after genome duplication events was driven by functional diversification.
Here we identify the sites at which positive selection is detected in the plant
B56 gene family, and discuss the significance of selection at these positions in
the context of PP2A holoenzyme structure. The pattern of positive selection
observed in the B11 subclade is distinctive, and suggests selective pressure on
interactions with substrates and the enzymatic core.
PMID- 28692337
TI - A multidisciplinary perioperative strategy for attaining "more physiologic"
cardiac surgery.
AB - BACKGROUND: Cardiac surgery is, by definition, a "non-physiologic" intervention
associated with systemic adverse effects. Despite advances in surgical technique,
cardiopulmonary bypass (CPB) technology as well as anaesthesia management and
patient care, there is still significant morbidity and subsequent mortality. AIM:
We consider that the contemporary demand for further improving patient outcome
mandates the upgrade from optimal perfusion during the procedure as the gold
standard to the concept of a "more physiologic" cardiac surgery. Our policy is a
multidisciplinary perioperative strategy based on goal-directed perfusion
throughout surgery incorporating in-line monitoring. This translates to "prevent
rather than correct" malperfusion through real-time adjustment rather than
correction of derangement detected late by incremental evaluation. METHOD: The
strategy is based on continuous monitoring of cardiac index, SvO2, DO2i,
DO2i/VCO2i and rSO2. Data acquisition is followed by action when needed; this
includes stepwise: transfusion, increase of cardiac output and initiation of
inotropic/vasoactive support. Moreover, implementation of minimally invasive
extracorporeal circulation (MiECC) is considered as a fundamental component of
physiologic perfusion when on-CPB, providing improved circulatory support and end
organ protection. CONCLUSION: We consider that, with this strategy which
establishes optimal perfusion perioperatively, we attain the goal of a "more
physiologic" cardiac surgery.
PMID- 28692338
TI - Evaluation of a novel point-of-care test for the rapid semi-quantitative
detection of allergen-specific immunoglobulin E.
AB - BACKGROUND: Allergen-specific IgE levels in human sera support the diagnosis of
allergies. However, commonly used laboratory tests are time consuming. The new
point-of-care test FastCheckPOC 20 (FCP20) allows the simultaneous and semi
quantitative evaluation of IgE antibodies for 20 aeroallergens and food
allergens. METHODS: Two hundred patients with allergic symptoms were included in
a multicenter performance evaluation using both whole blood and plasma or serum
samples. FCP20 results were compared with the skin prick test (SPT) and the
ImmunoCAP system (Phadia) which was used as reference for specific IgE values.
RESULTS: The concordance between FCP20 and ImmunoCAP was 76% for positive results
and 80% for negative results over 20 allergens. Overall agreement (accuracy) of
FCP20 with the ImmunoCAP was 80% across all 20 allergens. The concordance between
FCP20 and SPT over all 20 allergens was 66% for positive results and 71% for
negative results. Overall agreement of FCP20 with the SPT was 70%. Semi
quantitative FCP20 results (Levels 1-5) revealed nearly identical values for
whole blood and plasma/serum test results. A good concordance was also observed
between FCP20 levels and ImmunoCAP classes. CONCLUSIONS: FastCheckPOC 20 is
reliable to determine allergen-specific IgE in human whole blood and plasma/serum
samples.
PMID- 28692339
TI - Motivations for Selling Ecstasy among Young Adults in the Electronic Dance Music
Club Culture in Brazil.
AB - This article describes data on the motivations for selling ecstasy among young
adults in the electronic dance music (EDM) club culture in Brazil. Individual
interviews were conducted with 20 individuals recruited for their involvement in
the EDM club scene. Eligible participants were aged 18-39 and reported ecstasy
and/or LSD use one or more times in the past 90 days. Exclusion criteria included
current treatment for drug/alcohol problems and cognitive impairment or
clinically evident psychiatric disorder. Mean age was 22.92 (SD 2.77), 60% were
male, 45% reported 12 or more years of education, 50% did not have a primary
partner, 50% were living alone, and all had friends who also used ecstasy. Three
main themes emerged: (1) "easy" transition from ecstasy user to seller; (2)
desire to achieve popularity and fame; and (3) need to sell ecstasy to maintain
the high cost of EDM club scene participation. This is one of the first studies
of ecstasy sellers in Brazil. The results demonstrate the ease with which the
participants transition from ecstasy user to seller. Given the potential health
and social dangers associated with ecstasy use, public health campaigns to
prevent ecstasy use and policy initiatives to limit the ecstasy supply are
warranted.
PMID- 28692340
TI - Salivary cortisol and alpha-amylase: Is there consistency between psychosocial
stress test and burdensome work shifts?
AB - This study examined the consistency of salivary cortisol and alpha-amylase (sAA)
total daily secretion between laboratory and field circumstances. The 95
participants were shift working female health care professionals with high (n =
53) or low (n = 42) psychosocial stress (job strain) measured by the Job Content
Questionnaire (JCQ). The Trier Social Stress Test including a 5-min free speech
and a mental arithmetic task was conducted with four, and field measurements with
three daily saliva samples of cortisol and sAA during circadian rhythm and inter
shift recovery controlled morning shift, night shift, and a day off. The
associations of salivary cortisol and sAA area under the curve with respect to
ground (AUCg) and area under the curve with respect to increase (AUCi) between
laboratory and field were tested using OLS (Ordinary Least Squares) regression.
The sAA AUCg output in the laboratory was correlated with the output during all
field measurement days and similarly among high and low job strain groups (p <
0.001). SAA AUCi and salivary cortisol AUCg and AUCi were not correlated between
laboratory and field measurement, neither in the whole sample nor among the low
or high job strain group. In conclusion, a laboratory measure of sAA AUCg output
is promising in predicting stress-related output during burdensome work shifts
and leisure time, whereas sAA AUCi or salivary cortisol seem not to have this
potential.
PMID- 28692341
TI - The 2014 crude 4-methylcyclohexanemethanol chemical release and birth outcomes in
West Virginia.
AB - Approximately 10,000 gallons of crude 4-methylcyclohexanemethanol and propylene
glycol phenyl ether were accidentally released into the Elk River upstream from a
water treatment facility in West Virginia. The objective of this study was to use
logistic and Poisson regression analyses to determine the effect potential
exposures had on adverse birth outcomes (birth weight, small for gestational age,
and abnormal Apgar score). We adjusted for confounding factors and assessed
prevalence of adverse birth outcomes by residential location and timing of the
pregnancy. There were no statistically significant interactions between
residential location and timing of the pregnancy (range of p values: .157-.806).
Changes in the prevalence of birth outcomes were consistent before and after the
spill regardless of residential location. There was no evidence of an association
between adverse birth outcomes and potential exposure to the released chemicals.
PMID- 28692342
TI - Targeting the alpha4-alpha5 interface of RAS results in multiple levels of
inhibition.
AB - Generation of RAS-targeted therapeutics has long been considered a "holy grail"
in cancer research. However, a lack of binding pockets on the surface of RAS and
its picomolar affinity for guanine nucleotides have made isolation of inhibitors
particularly challenging. We recently described a monobody, termed NS1, that
blocks RAS signaling and oncogenic transformation. NS1 binds to the alpha4-beta6
alpha5 interface of H-RAS and K-RAS thus preventing RAS dimerization and
nanoclustering, which in turn prevents RAS-stimulated dimerization and activation
of RAF. Interestingly, NS1 reduces interaction of oncogenic K-RAS, but not H-RAS,
with RAF and reduces K-RAS plasma membrane localization. Here, we show that these
isoform specific effects of NS1 on RAS:RAF are due to the distinct hypervariable
regions of RAS isoforms. NS1 inhibited wild type RAS function by reducing RAS GTP
levels. These findings reveal that NS1 disrupts RAS signaling through a mechanism
that is more complex than simply inhibiting RAS dimerization and nanoclustering.
PMID- 28692344
TI - The Impact of the ASAP Trial: Maybe We Shouldn't Act So Quickly.
PMID- 28692343
TI - Pulsotype Diversity of Clostridium botulinum Strains Containing Serotypes A
and/or B Genes.
AB - Clostridium botulinum strains are prevalent in the environment and produce a
potent neurotoxin that causes botulism, a rare but serious paralytic disease. In
2010, a national PulseNet database was established to curate C. botulinum
pulsotypes and facilitate epidemiological investigations, particularly for
serotypes A and B strains frequently associated with botulism cases in the United
States. Between 2010 and 2014 we performed pulsed-field gel electrophoresis
(PFGE) using a PulseNet protocol, uploaded the resulting PFGE patterns into a
national database, and analyzed data according to PulseNet criteria (UPGMA
clustering, Dice coefficient, 1.5% position tolerance, and 1.5% optimization). A
retrospective data analysis was undertaken on 349 entries comprised of type A and
B strains isolated from foodborne and infant cases to determine epidemiological
relevance, resolution of the method, and the diversity of the database. Most
studies to date on the pulsotype diversity of C. botulinum have encompassed very
small sets of isolates; this study, with over 300 isolates, is more comprehensive
than any published to date. Epidemiologically linked isolates had
indistinguishable patterns, except in four instances and there were no obvious
geographic trends noted. Simpson's Index of Diversity (D) has historically been
used to demonstrate species diversity and abundance within a group, and is
considered a standard descriptor for PFGE databases. Simpson's Index was
calculated for each restriction endonuclease (SmaI, XhoI), the pattern
combination SmaI-XhoI, as well as for each toxin serotype. The D values indicate
that both enzymes provided better resolution for serotype B isolates than
serotype A. XhoI as the secondary enzyme provided little additional
discrimination for C. botulinum. SmaI patterns can be used to exclude unrelated
isolates during a foodborne outbreak, but pulsotypes should always be considered
concurrently with available epidemiological data.
PMID- 28692345
TI - Emotional intelligence and OCB: The moderating role of work locus of control.
AB - This study sought to identify linkages between Mayer, Salovey, and Caruso's
(2008) four dimensions of emotional intelligence (EI) and organizational
citizenship behavior, and the moderating influence of locus of control. Using a
sample of 290 employed students, the present study examines the effects of the
dimensions of EI on OCB directed at individuals (OCB-I) and OCB directed at the
organization (OCB-O). Emotionally intelligent individuals were hypothesized to
engage in more organizational citizenship behavior (OCB) than individuals with
lower EI. Work locus of control was hypothesized to moderate the emotional
intelligence-OCB linkage, with high internals having a stronger emotional
intelligence to OCB linkage. Results indicate that the EI dimensions of
perceiving, understanding, and managing emotions had positive effects on OCB-I
and OCB-O. Using emotions was not linked to OCB. Locus of control strengthened
the EI to OCB-I link, but had no effect on the OCB-O linkage.
PMID- 28692346
TI - The validation of an LC-MS/MS assay for perhexiline and major hydroxy
metabolites, and its application to therapeutic monitoring in patient plasma.
AB - AIM: Perhexiline (PEX), being developed to treat hypertrophic cardiomyopathy, is
toxic at levels above the therapeutic range. Plasma level monitoring is therefore
essential. The absence of a UV-absorbing chromophore has in the past required
quantitative analysis of PEX in plasma using lengthy derivatization methods,
followed by HPLC and fluorescence detection. The routine and urgent analysis of a
large number of patient plasma samples necessitates faster and reliable
analytical methodology. RESULTS: An LC-MS/MS method, using two novel internal
standards, has been validated for the quantitative measurement of PEX and its
major hydroxy metabolites in human plasma. CONCLUSION: The assay has been applied
to therapeutic drug monitoring (TDM), where PEX and the ratio of the drug to cis
hydroxy perhexiline, were measured at designated intervals.
PMID- 28692347
TI - Prevalence of difficult intubation and failed intubation in a diverse obstetric
community-based population.
AB - OBJECTIVE: To describe the incidence of difficult and failed intubations in
obstetric patients during a 6 year period monitored by a quality assurance
program together with American Society of Anesthesiologists Physical Status (ASA
PS) scores, and obesity (body mass index >30 kg/m2). METHODS: Following
Institutional Review Board approval, data about obstetric patients who
experienced unanticipated difficult or failed intubations from 2010 to 2015 was
obtained from the quality assurance database of a large, community-based
anesthesiology group practice. The database employs standardized definitions for
difficult intubation (>3 laryngoscopic attempts by experienced providers) and
failed intubation (inability to intubate leading to surgical airway or waking up
the patient). ASA PS scores and comorbidities were also identified for obstetric
general anesthetics using an internally developed quality assurance program,
Quantum Clinical Navigation System. RESULTS: There were 2802 obstetric general
anesthetics in the database of which 1085 (38.7%) were deemed as emergencies.
There were no cases of failed intubation and seven cases of unanticipated
difficult intubations (1:400 cases, 0.25% of all obstetric general anesthetics,
95% confidence interval 0.1-0.5%), six of which occurred during emergency
surgery. There was an increase in obesity (p = .003) and ASA PS (p = .02) over
the period of the study. The incidence of difficult intubation was not found to
be significantly changed (p = .68). CONCLUSIONS: Despite an increase in ASA PS
score and obesity, there was no increase in the incidence of difficult intubation
in obstetric patients. Limitations of the study include its retrospective design,
and the small number of difficult intubation cases identified.
PMID- 28692348
TI - The G allele of MMP12 -82 A > G promoter polymorphism as a protective factor for
COPD in Bulgarian population.
AB - Chronic inflammation and remodelling of the small airways are features related to
chronic obstructive pulmonary disease (COPD). In the current study, we aimed to
explore the possible role of MMP12 -82 A > G (rs2276109) promoter polymorphism in
the development of COPD in a population from Bulgaria (167 patients with COPD and
119 control individuals). The genotype and allele distributions differed
significantly between COPD patients and controls (p = .010 and p = .043,
respectively, chi2 test). The genotypes containing at least one variant G allele
(AA + GG) were more frequent in the control group than in patients (36.1% vs.
22.2%) determining 2.96-fold lower risk for COPD after adjustment for age, sex
and smoking habits (OR = 0.338, 95%CI: 0.168-0.682, p = .002). Our results
suggest that carriers of genotypes with at least one copy of minor G allele of
rs2276109 might have lower risk for COPD development, with no marked effect on
the lung function and severity of the disease.
PMID- 28692349
TI - Sexual Health in Children and Adolescents.
PMID- 28692350
TI - The muscular dystrophic chicken is hypernatremic.
AB - 1. The E3 ubiquitin protein ligase 1 (WWP1) gene, the mutation of which causes
muscular dystrophy in chickens, is expressed not only in the pectoral muscle, but
also in a number of tissues such as the kidney. Therefore, this study examined
some parameters related to kidney function in muscular dystrophic (MD) chickens.
2. Plasma osmolality, Na+ and K+ concentrations, aldosterone levels, and the
expression of aquaporin (AQP) 2, AQP3, and alpha subunits of the amiloride
sensitive epithelial sodium channel (alphaENaC) were analysed in the kidneys of 5
week-old MD chickens and White Leghorn (WL) chickens under physiological
conditions or after one day of water deprivation. 3. Plasma osmolality, Na+
concentrations, and plasma aldosterone levels were significantly higher in MD
chickens than in WL chickens. alphaENaC mRNA expression levels were lower in MD
chickens than in WL chickens. AQP2 and AQP3 mRNA expression levels were similar
in the two strains of chickens. 4. Plasma osmolality correlated with aldosterone
levels and AQP2 and alphaENaC mRNA levels in WL chickens. In MD chickens, plasma
osmolality correlated with AQP2 mRNA levels, but not with plasma aldosterone or
alphaENaC mRNA levels. 5. These results suggest that neither water reabsorption
nor the expression of AQP2 and AQP3 is impaired in MD chickens and that a WWP1
gene mutation may or may not directly induce an abnormality in Na+-reabsorption
in the kidneys of MD chickens, potentially through alphaENaC.
PMID- 28692351
TI - Still Lost in Transition?
AB - Numerous policy directives highlight the need for planned and well-coordinated
support to enable young people with long-term conditions and disabilities to
negotiate the transition to adulthood, including making the leap from children
oriented to adult- centered health services. The journey is complex and multi
dimensional. For young people with a disability, long-term condition, or mental
health problem there are additional challenges when transitioning between
services with differences in expectations, delivery, and culture. This article
explores findings from 6 case studies of young people who have recently
experienced transition to adult health and care services, triangulating inter
related perspectives: those of young people, parents, and carers, and where
possible the professionals involved. One of the case studies illustrates how the
challenges are actually experienced. Analysis of emerging themes across the case
studies leads to key messages from families to inform strategic development of
services and practice.
PMID- 28692352
TI - Responsiveness and discriminant validity of the Child and Adolescent Scale of
Participation across three years for children and youth with traumatic brain
injury.
AB - PURPOSE: To examine responsiveness and discriminant validity of the Child and
Adolescent Scale of Participation (CASP) across three years. METHODS: Examined
longitudinal data on 515 children and youth with TBI and arm injuries. Repeated
measures analyses of variance were used to examine CASP scores (pre-injury; 3,
12, 24, 36 months post-injury). RESULTS: Scores decreased from pre-injury to 3
months, but significantly only for moderate and severe TBI groups. Scores
gradually increased post-injury for all groups except severe TBI. Scores were
consistently lowest for severe TBI, followed by moderate TBI, mild TBI, and arm
injury across time. Severe TBI scores were significantly lower than scores for
mild TBI and arm injury, but not moderate TBI. CONCLUSIONS: CASP scores were
responsive to change over time at most measurements and differentiated between
groups, particularly severe TBI. Further research is needed with a larger sample
of children with moderate/severe TBI as they were underrepresented in this study.
PMID- 28692353
TI - Fractional carbon dioxide (CO2) laser combined with topical tretinoin for the
treatment of different forms of cystic acne.
AB - Nodulocystic acne is prone to scarring and difficult to treat with treatments
other than oral isotretinoin. The aim of this article is to discuss the role of a
single session of a fractional carbon dioxide (CO2) laser combined with a topical
treatment with a tretinoin and antibiotic gel for a month as a successful
treatment to improve nodulocystic acne and chronic microcystic acne. Two cases
were involved: the first with nodulocystic acne lesions that persisted after oral
retinoids and the second with chronic microcystic acne resistant to topical
treatments. After only one session of treatment with the CO2 laser and the
topical treatment, a complete healing of the nodulocystic acne lesions was
observed with minimal secondary effects. The microcystic acne showed great
improvement. No other topical or oral treatment was needed. This treatment could
be a safe and effective treatment for nodulocystic acne lesions and microcystic
acne when other treatments fail. More studies should be performed to confirm our
results.
PMID- 28692354
TI - Potential protective effects of polysaccharide extracted from Ulva lactuca
against male reprotoxicity induced by thiacloprid.
AB - CONTEXT: Polysaccharides (PSs) from seaweeds have been reported to possess
biological activity of potential medicinal values. OBJECTIVE: The current study
was conducted to establish the protective effects of PS extracted from Ulva
lactuca against oxidative stress induced by Thiacloprid (THC) in the rat
reproductive system. MATERIALS AND METHODS: Rats were exposed either to THC, THC
+ PS (100 mg/kg), or THC + PS (200 mg/kg). RESULTS: Our study showed that THC
induced severe disorders in the functional sperm parameters. A decrease in
antioxidant activities and their genes expression were observed in the same
group, compared to the controls. Our molecular data showing also a severe DNA
breakdown in the testis of THC treated group. Moreover, THC treated group showed
severe histopathological changes. CONCLUSIONS: Our results revealed that PS
extracted from Ulva lactuca alleviated the THC induced reprotoxicity and reduced
oxidative stress damages, DNA breakdown and histological injuries in the testis.
PMID- 28692355
TI - Teaching clinical reasoning to medical students.
AB - Clinical reasoning is often not explicitly addressed in the early medical school
curriculum. As a result, students observe the process while on clinical
placements with little or no understanding of the complex processes underlying
it. Clinical reasoning has significant implications for patient safety. Medical
errors as a consequence of faulty reasoning contribute to patient morbidity and
mortality. Educating medical students at an early stage about the processes of
clinical reasoning and strategies to avoid associated errors can have positive
impacts upon patient safety. The authors propose that clinical reasoning should
be taught as early as the first year of medical school, using frameworks,
anatomical knowledge and mnemonics. Using this approach with simulated cases
during the pre-clinical years, students will be equipped with an understanding of
the clinical reasoning process as it unfolds before them while on clinical
placements, enhancing their overall learning experience.
PMID- 28692356
TI - Benign acute childhood myositis secondary to parainfluenza A virus.
PMID- 28692357
TI - Should clinicians have a role in financial decision making in the NHS?
PMID- 28692358
TI - Registry data allow great progress, but must be interpreted with caution.
PMID- 28692359
TI - Prevention of limb length discrepancy in total hip arthroplasty.
AB - Total hip arthroplasty is a highly effective and cost-efficient procedure but
postoperative limb length discrepancy is a common source of patient
dissatisfaction and litigation. This article provides a systematic, stepwise
approach for identifying and proactively managing risk factors associated with
limb length discrepancy following total hip arthroplasty. This review explores
preoperative history taking, clinical examination, radiological templating,
implant positioning, soft tissue balancing, and intraoperative surgical
techniques for minimizing leg length discrepancy while maintaining stability and
restoring mechanical function following total hip arthroplasty. A comprehensive
understanding of the multifactorial nature and methods for reducing postoperative
limb length discrepancy is essential for optimizing patient satisfaction,
clinical outcomes and long-term function following total hip arthroplasty.
PMID- 28692360
TI - A non-traumatic lump on the chest wall: isolated bifid rib.
PMID- 28692361
TI - Learning from error: leading a culture of safety.
AB - A recent shift towards more collective leadership in the NHS can help to achieve
a culture of safety, particularly through encouraging frontline staff to
participate and take responsibility for improving safety through learning from
error and near misses. Leaders must ensure that they provide psychological
safety, organizational fairness and learning systems for staff to feel confident
in raising concerns, that they have the autonomy and skills to lead continual
improvement, and that they have responsibility for spreading this learning within
and across organizations.
PMID- 28692362
TI - The academic foundation programme: a new foundation for academic medicine.
PMID- 28692363
TI - ST elevation myocardial infarction after coronary artery spasm with no clear
trigger.
PMID- 28692364
TI - Clinical News.
PMID- 28692365
TI - Robotic surgery in hip and knee arthroplasty.
AB - This article provides an overview of current use of robotics in hip and knee
arthroplasty. Several studies have reported radiographic improvements in joint
alignment using robotic-assisted arthroplasty surgery. The economic case made for
introducing robotics in joint arthroplasty largely focuses on the hypothesis of
reduced hospital stay and reduction in the rate of revisions. This awaits robust
data from long-term studies along with the documentation of clinical benefits
that will follow the larger implementation of robotic-assisted surgery. However,
modern robotic systems offer an opportunity for reproducible implementation of a
preoperative plan, with low complication rates. Growing clinical use may in
future present robust data demonstrating an appreciable clinical benefit that
justifies the large scale clinical use of robotic technology.
PMID- 28692366
TI - Laryngeal mask airway or endotracheal tube for tonsillectomy? An update.
PMID- 28692367
TI - The deaths of the Alexander Monros, distinguished Scottish anatomists.
PMID- 28692369
TI - Choice of oral anticoagulants in older patients with non-valvular atrial
fibrillation.
PMID- 28692370
TI - An intrathoracic rib in a 3-year-old boy.
PMID- 28692371
TI - Chronic hepatitis in the transplant patient.
PMID- 28692372
TI - Cerebral venous sinus thrombosis.
PMID- 28692373
TI - Wound dressings.
PMID- 28692374
TI - Is there a role for stem cells in treating articular injury?
AB - Articular cartilage is a specialized tissue with a high prevalence of injuries.
The complex architecture of articular cartilage means that injuries are difficult
to treat. The sequelae of such injuries include post-traumatic osteoarthritis.
Current treatments include microfracture, microdrilling, osteochondral
transplantation and matrix autologous chondral implantation. However, current
surgical therapies have a number of disadvantages. Mesenchymal stem cells have
been suggested as a potential alternative therapy, with a theoretical ability to
regenerate articular cartilage. Research, although positive, is mainly limited to
case series, in which the follow up is short to medium term. Stem cells may hold
the answer to the age-old problem of articular cartilage injury but more robust
evidence is required.
PMID- 28692375
TI - Non-invasive imaging in cardiology for the generalist.
AB - In contrast to invasive techniques, the goal of non-invasive cardiac imaging is
to identify or exclude heart disease in response to a patient's clinical history
of cardiac localizing symptoms. Imaging also aims to establish the risk of an
individual developing future heart disease with a view to preventing major
cardiovascular events such as myocardial infarction. As well as a role in risk
stratification, non-invasive cardiac imaging also helps with decision making for
future medical and procedural interventions. This review outlines the non
invasive imaging modalities available to physicians to identify and risk stratify
cardiovascular disease. It discusses the strengths of each imaging technique, in
which circumstances it is most useful and its diagnostic accuracy.
PMID- 28692377
TI - The interprofessional learning experience: Findings from a qualitative study
based in an outpatient setting.
AB - Clinical interprofessional education has traditionally taken place in hospital
wards, but much diagnosis and treatment have shifted to the outpatient setting.
The logical consequence is to shift more students' clinical placements from the
"bedside" to outpatient settings. However, it is unclear how we ensure that this
shift maximises learning. The purpose of this article is to understand the
authentic learning experience in an interprofessional outpatient clinic setting.
We performed an exploratory case study with interviews of four nursing students,
13 medical students, and six staff members who worked in an interprofessional
outpatient orthopaedic clinic from March 2015 to January 2016. The interviews
were transcribed and analysed using systematic text condensation. The students'
self-reported learning experience in this outpatient clinic was characterised by
direct patient contact and by authentic, interprofessional, task-based learning,
and a preference for indirect supervision when conducting uncomplicated patient
consultations. The supervisors intended to create this interprofessional
outpatient clinic experience by having a clear teaching approach based on adult
learning principles in a safe and challenging learning environment. The shift to
the outpatient setting was strongly and practically supported by the management.
This study indicates that student learning can be shifted to the outpatient
clinic setting if there is supportive management and dedicated supervisors who
establish a challenging yet safe interprofessional learning environment.
PMID- 28692376
TI - Multiplex Staining by Sequential Immunostaining and Antibody Removal on Routine
Tissue Sections.
AB - Multiplexing, labeling for multiple immunostains in the very same cell or tissue
section in situ, has raised considerable interest. The methods proposed include
the use of labeled primary antibodies, spectral separation of fluorochromes,
bleaching of the fluorophores or chromogens, blocking of previous antibody
layers, all in various combinations. The major obstacles to the diffusion of this
technique are high costs in custom antibodies and instruments, low throughput,
and scarcity of specialized skills or facilities. We have validated a method
based on common primary and secondary antibodies and diffusely available
fluorescent image scanners. It entails rounds of four-color indirect
immunofluorescence, image acquisition, and removal (stripping) of the antibodies,
before another stain is applied. The images are digitally registered and the
autofluorescence is subtracted. Removal of antibodies is accomplished by
disulfide cleavage and a detergent or by a chaotropic salt treatment, this latter
followed by antigen refolding. More than 30 different antibody stains can be
applied to one single section from routinely fixed and embedded tissue. This
method requires a modest investment in hardware and materials and uses freeware
image analysis software. Multiplexing on routine tissue sections is a high
throughput tool for in situ characterization of neoplastic, reactive,
inflammatory, and normal cells.
PMID- 28692378
TI - Photosynthetic activity of cotyledons is critical during post-germinative growth
and seedling establishment.
AB - Thioredoxins (Trxs) play a relevant role in thiol-dependent redox regulation,
which allows the rapid adaptation of chloroplast metabolism to unpredictable
environmental conditions. In chloroplasts, Trxs use reducing equivalents provided
by photoreduced ferredoxin (Fdx) via the action of a ferredoxin-thioredoxin
reductase (FTR), thus linking redox regulation to light. In addition, these
organelles contain an NADPH-thioredoxin reductase, NTRC, with a Trx domain at the
C-terminus. NTRC efficiently reduces 2-Cys peroxiredoxins (Prxs), hence having
antioxidant function. However, NTRC also participates in the redox regulation of
processes, such as starch and chlorophyll biosynthesis, which are known to be
regulated by Trxs. Thus, the question arising is whether there is a cross-talk
between the 2 redox systems. Arabidopsis mutants simultaneously devoid of NTRC
and Trx x or Trxs f show a dramatic growth inhibition phenotype, indicating that
NTRC is required for the function of these unrelated Trxs. Remarkably, both the
ntrc-trxx double mutant and, to a higher extent, the ntrc-trxf1f2 triple mutant
show high mortality at the seedling stage, which is rescued by sucrose. These
findings show the relevant role of redox regulation for chloroplast performance
and uncover the key function of cotyledons chloroplasts at the transition to
autotrophic metabolism during seedling establishment.
PMID- 28692380
TI - Haploidentical Hematopoietic Cell Transplantation Using Post-Transplantation
Cyclophosphamide: Does Graft Source Matter?
PMID- 28692379
TI - Macrocyclic peptides decrease c-Myc protein levels and reduce prostate cancer
cell growth.
AB - The oncoprotein c-Myc is often overexpressed in cancer cells, and the stability
of this protein has major significance in deciding the fate of a cell. Thus,
targeting c-Myc levels is an attractive approach for developing therapeutic
agents for cancer treatment. In this study, we report the anti-cancer activity of
the macrocyclic peptides [D-Trp]CJ-15,208 (cyclo[Phe-D-Pro-Phe-D-Trp]) and the
natural product CJ-15,208 (cyclo[Phe-D-Pro-Phe-Trp]). [D-Trp]CJ-15,208 reduced c
Myc protein levels in prostate cancer cells and decreased cell proliferation with
IC50 values ranging from 2.0 to 16 uM in multiple PC cell lines. [D-Trp]CJ-15,208
induced early and late apoptosis in PC-3 cells following 48 hours treatment, and
growth arrest in the G2 cell cycle phase following both 24 and 48 hours
treatment. Down regulation of c-Myc in PC-3 cells resulted in loss of sensitivity
to [D-Trp]CJ-15,208 treatment, while overexpression of c-Myc in HEK-293 cells
imparted sensitivity of these cells to [D-Trp]CJ-15,208 treatment. This
macrocyclic tetrapeptide also regulated PP2A by reducing the levels of its
phosphorylated form which regulates the stability of cellular c-Myc protein. Thus
[D-Trp]CJ-15,208 represents a new lead compound for the potential development of
an effective treatment of prostate cancer.
PMID- 28692381
TI - Unlocking the Mystery of Small-Cell Lung Cancer Transformations in EGFR Mutant
Adenocarcinoma.
PMID- 28692382
TI - Use of Biomarkers to Guide Decisions on Adjuvant Systemic Therapy for Women With
Early-Stage Invasive Breast Cancer: American Society of Clinical Oncology
Clinical Practice Guideline Focused Update.
AB - Purpose This focused update addresses the use of MammaPrint (Agendia, Irvine, CA)
to guide decisions on the use of adjuvant systemic therapy. Methods ASCO uses a
signals approach to facilitate guideline updates. For this focused update, the
publication of the phase III randomized MINDACT (Microarray in Node-Negative and
1 to 3 Positive Lymph Node Disease May Avoid Chemotherapy) study to evaluate the
MammaPrint assay in 6,693 women with early-stage breast cancer provided a signal.
An expert panel reviewed the results of the MINDACT study along with other
published literature on the MammaPrint assay to assess for evidence of clinical
utility. Recommendations If a patient has hormone receptor-positive, human
epidermal growth factor receptor 2 (HER2)-negative, node-negative breast cancer,
the MammaPrint assay may be used in those with high clinical risk to inform
decisions on withholding adjuvant systemic chemotherapy due to its ability to
identify a good-prognosis population with potentially limited chemotherapy
benefit. Women in the low clinical risk category did not benefit from
chemotherapy regardless of genomic MammaPrint risk group. Therefore, the
MammaPrint assay does not have clinical utility in such patients. If a patient
has hormone receptor-positive, HER2-negative, node-positive breast cancer, the
MammaPrint assay may be used in patients with one to three positive nodes and a
high clinical risk to inform decisions on withholding adjuvant systemic
chemotherapy. However, such patients should be informed that a benefit from
chemotherapy cannot be excluded, particularly in patients with greater than one
involved lymph node. The clinician should not use the MammaPrint assay to guide
decisions on adjuvant systemic therapy in patients with hormone receptor
positive, HER2-negative, node-positive breast cancer at low clinical risk, nor
any patient with HER2-positive or triple-negative breast cancer, because of the
lack of definitive data in these populations. Additional information can be found
at www.asco.org/breast-cancer-guidelines and www.asco.org/guidelineswiki .
PMID- 28692383
TI - Occupational Therapy in the Intensive Care Unit: A Systematic Review.
AB - This paper is a synthesis of the available literature on occupational therapy
interventions performed in the adult intensive care unit (ICU). The databases of
Ovid MEDLINE, Embase, the Cochrane Library, ClinicalTrials.gov and CINAHL
databases were systematically searched from inception through August 2016 for
studies of adults who received occupational therapy interventions in the ICU. Of
1,938 citations reviewed, 10 studies met inclusion criteria. Only one study
explicitly discussed occupational therapy interventions performed and only one
study specifically tested the efficacy of occupational therapy. Future research
is needed to clarify the specific interventions and role of occupational therapy
in the ICU and the efficacy of these interventions.
PMID- 28692384
TI - Advancing the Use of Emergency Department Syndromic Surveillance Data, New York
City, 2012-2016.
AB - INTRODUCTION: The use of syndromic surveillance has expanded from its initial
purpose of bioterrorism detection. We present 6 use cases from New York City that
demonstrate the value of syndromic surveillance for public health response and
decision making across a broad range of health outcomes: synthetic cannabinoid
drug use, heat-related illness, suspected meningococcal disease, medical needs
after severe weather, asthma exacerbation after a building collapse, and Ebola
like illness in travelers returning from West Africa. MATERIALS AND METHODS: The
New York City syndromic surveillance system receives data on patient visits from
all emergency departments (EDs) in the city. The data are used to assign syndrome
categories based on the chief complaint and discharge diagnosis, and analytic
methods are used to monitor geographic and temporal trends and detect clusters.
RESULTS: For all 6 use cases, syndromic surveillance using ED data provided
actionable information. Syndromic surveillance helped detect a rise in synthetic
cannabinoid-related ED visits, prompting a public health investigation and
action. Surveillance of heat-related illness indicated increasing health effects
of severe weather and led to more urgent public health messaging. Surveillance of
meningitis-related ED visits helped identify unreported cases of culture-negative
meningococcal disease. Syndromic surveillance also proved useful for assessing a
surge of methadone-related ED visits after Superstorm Sandy, provided reassurance
of no localized increases in asthma after a building collapse, and augmented
traditional disease reporting during the West African Ebola outbreak. PRACTICE
IMPLICATIONS: Sharing syndromic surveillance use cases can foster new ideas and
build capacity for public health preparedness and response.
PMID- 28692385
TI - Local Public Health Surveillance of Heroin-Related Morbidity and Mortality,
Orange County, Florida, 2010-2014.
AB - OBJECTIVES: Heroin-related deaths have increased substantially in the past 10
years in the United States, particularly in Florida. Our objectives were to
measure heroin-related morbidity and mortality rates in Orange County, Florida,
and to assess trends in those rates during 2010-2014. METHODS: We used 3 heroin
surveillance methods, based on data from the Florida Medical Examiner, the
Florida Agency for Health Care Administration (AHCA), and the Electronic
Surveillance System for the Early Notification of Community-Based Epidemics
Florida (ESSENCE-FL). We conducted descriptive and geographic spatial analyses of
all 3 data sets, determined heroin-related mortality and morbidity (emergency
department [ED] visit) rates, and compared the timeliness of data availability
from the 3 data sources. RESULTS: Heroin-related deaths in Orange County
increased by 590%, from 10 in 2010 to 69 in 2014. Heroin-related ED visits during
the same period increased 12-fold (from 13 to 154) and 6-fold (from 49 to 307)
when based on AHCA and ESSENCE-FL data, respectively. ESSENCE-FL identified 140%
more heroin-related visits than did AHCA. Spatial analysis found geographic
clustering of heroin-related morbidity and mortality. Hospitals facing the
greatest burden of heroin-related ED visits were close to communities with the
highest crude heroin-related ED visit rates. Of the 3 data sources, ESSENCE-FL
provided the timeliest data availability. CONCLUSIONS: These 3 data sources can
be considered acceptable surveillance systems for monitoring heroin-related
events in Orange County. The timely availability of data from ESSENCE-FL makes it
the most useful source for obtaining near-real-time data about the heroin
epidemic, potentially leading to improved identification of populations most in
need of interventions to reduce morbidity and mortality.
PMID- 28692386
TI - The Evolution of BioSense: Lessons Learned and Future Directions.
AB - The BioSense program was launched in 2003 with the aim of establishing a
nationwide integrated public health surveillance system for early detection and
assessment of potential bioterrorism-related illness. The program has matured
over the years from an initial Centers for Disease Control and Prevention-centric
program to one focused on building syndromic surveillance capacity at the state
and local level. The uses of syndromic surveillance have also evolved from an
early focus on alerts for bioterrorism-related illness to situational awareness
and response, to various hazardous events and disease outbreaks. Future
development of BioSense (now the National Syndromic Surveillance Program)
includes, in the short term, a focus on data quality with an emphasis on
stability, consistency, and reliability and, in the long term, increased capacity
and innovation, new data sources and system functionality, and exploration of
emerging technologies and analytics.
PMID- 28692387
TI - Syndromic Surveillance Revolution? Public Health Benefits of Modernizing the
Emergency Care Patient Health Record in England.
PMID- 28692388
TI - Detecting Suicide-Related Emergency Department Visits Among Adults Using the
District of Columbia Syndromic Surveillance System.
AB - OBJECTIVES: Limited studies have examined the usefulness of syndromic
surveillance to monitor emergency department (ED) visits involving suicidal
ideation or attempt. The objectives of this study were to (1) examine whether
syndromic surveillance of chief complaint data can detect suicide-related ED
visits among adults and (2) assess the added value of using hospital ED data on
discharge diagnoses to detect suicide-related visits. METHODS: The study data
came from the District of Columbia electronic syndromic surveillance system,
which provides daily information on ED visits at 8 hospitals in Washington, DC.
We detected suicide-related visits by searching for terms in the chief complaints
and discharge diagnoses of 248 939 ED visits for which data were available for
October 1, 2015, to September 30, 2016. We examined whether detection of suicide
related visits according to chief complaint data, discharge diagnosis data, or
both varied by patient sex, age, or hospital. RESULTS: The syndromic surveillance
system detected 1540 suicide-related ED visits, 950 (62%) of which were detected
through chief complaint data and 590 (38%) from discharge diagnosis data. The
source of detection for suicide-related ED visits did not vary by patient sex or
age. However, whether the suicide-related terms were mentioned in the chief
complaint or discharge diagnosis differed across hospitals. CONCLUSIONS: ED
syndromic surveillance systems based on chief complaint data alone would
underestimate the number of suicide-related ED visits. Incorporating the
discharge diagnosis into the case definition could help improve detection.
PMID- 28692389
TI - Evaluation of the Components of the North Carolina Syndromic Surveillance System
Heat Syndrome Case Definition.
AB - OBJECTIVES: To improve heat-related illness surveillance, we evaluated and
refined North Carolina's heat syndrome case definition. METHODS: We analyzed
North Carolina emergency department (ED) visits during 2012-2014. We evaluated
the current heat syndrome case definition (ie, keywords in chief complaint/triage
notes or International Classification of Diseases, Ninth Revision, Clinical
Modification [ ICD-9-CM] codes) and additional heat-related inclusion and
exclusion keywords. We calculated the positive predictive value and sensitivity
of keyword-identified ED visits and manually reviewed ED visits to identify true
positives and false positives. RESULTS: The current heat syndrome case definition
identified 8928 ED visits; additional inclusion keywords identified another 598
ED visits. Of 4006 keyword-identified ED visits, 3216 (80.3%) were captured by 4
phrases: "heat ex" (n = 1674, 41.8%), "overheat" (n = 646, 16.1%), "too hot" (n =
594, 14.8%), and "heatstroke" (n = 302, 7.5%). Among the 267 ED visits identified
by keyword only, a burn diagnosis or the following keywords resulted in a false
positive rate >95%: "burn," "grease," "liquid," "oil," "radiator," "antifreeze,"
"hot tub," "hot spring," and "sauna." After applying the revised inclusion and
exclusion criteria, we identified 9132 heat-related ED visits: 2157 by keyword
only, 5493 by ICD-9-CM code only, and 1482 by both (sensitivity = 27.0%, positive
predictive value = 40.7%). Cases identified by keywords were strongly correlated
with cases identified by ICD-9-CM codes (rho = .94, P < .001). CONCLUSIONS:
Revising the heat syndrome case definition through the use of additional
inclusion and exclusion criteria substantially improved the accuracy of the
surveillance system. Other jurisdictions may benefit from refining their heat
syndrome case definition.
PMID- 28692390
TI - Use of Emergency Department Data to Monitor and Respond to an Increase in Opioid
Overdoses in New Hampshire, 2011-2015.
AB - OBJECTIVES: Opioid-related overdoses and deaths in New Hampshire have increased
substantially in recent years, similar to increases observed across the United
States. We queried emergency department (ED) data in New Hampshire to monitor
opioid-related ED encounters as part of the public health response to this health
problem. METHODS: We obtained data on opioid-related ED encounters for the period
January 1, 2011, through December 31, 2015, from New Hampshire's syndromic
surveillance ED data system by querying for (1) chief complaint text related to
the words "fentanyl," "heroin," "opiate," and "opioid" and (2) opioid-related
International Classification of Diseases ( ICD) codes. We then analyzed the data
to calculate frequencies of opioid-related ED encounters by age, sex, residence,
chief complaint text values, and ICD codes. RESULTS: Opioid-related ED encounters
increased by 70% during the study period, from 3300 in 2011 to 5603 in 2015; the
largest increases occurred in adults aged 18-29 and in males. Of 20 994 total
opioid-related ED visits, we identified 18 554 (88%) using ICD code alone, 690
(3%) using chief complaint text alone, and 1750 (8%) using both chief complaint
text and ICD code. For those encounters identified by ICD code only, the
corresponding chief complaint text included varied and nonspecific words, with
the most common being "pain" (n = 3335, 18%), "overdose" (n = 1555, 8%),
"suicidal" (n = 816, 4%), "drug" (n = 803, 4%), and "detox" (n = 750, 4%). Heroin
specific encounters increased by 827%, from 4% of opioid-related encounters in
2011 to 24% of encounters in 2015. CONCLUSIONS: Opioid-related ED encounters in
New Hampshire increased substantially from 2011 to 2015. Data from New
Hampshire's ED syndromic surveillance system provided timely situational
awareness to public health partners to support the overall response to the opioid
epidemic.
PMID- 28692391
TI - Harnessing Syndromic Surveillance Emergency Department Data to Monitor Health
Impacts During the 2015 Special Olympics World Games.
AB - INTRODUCTION: Mass gatherings that attract a large international presence may
cause or amplify point-source outbreaks of emerging infectious disease. The Los
Angeles County Department of Public Health customized its syndromic surveillance
system to detect increased syndrome-specific utilization of emergency departments
(EDs) and other medical encounters coincident to the 2015 Special Olympics World
Games. MATERIALS AND METHODS: We queried live databases containing data on ED
visits, California Poison Control System calls, and Los Angeles County coroner
investigated deaths for increases in daily counts from July 19 to August 6, 2015.
We chose syndrome categories based on the potential for disease outbreaks common
to international travel and dormitory settings, morbidity amplified by high
temperatures, and bioterrorism threats inherent to mass gatherings. We performed
line-list reviews and trend analyses of total, syndrome-specific, and region
specific daily counts, using cumulative sum-based signals. We also piloted a
novel strategy of requesting that ED registrars proactively tag Special Olympics
attendees in chief complaint data fields. RESULTS: The syndromic surveillance
system showed that the 2015 Special Olympics did not generate large-scale acute
morbidities leading to detectable stress on local EDs. We recruited 10 hospitals
for proactive patient tagging, from which 16 Special Olympics attendees were
detected; these patients reported various symptoms, such as injury, vomiting, and
syncope. PRACTICE IMPLICATIONS: As an enhancement to traditional syndromic
surveillance, proactive patient tagging can illuminate potential epidemiologic
links among patients in challenging syndromic surveillance applications, such as
mass gatherings. Syndromic surveillance has the potential to enhance ED patient
polling and reporting of exposure, symptom, and other epidemiologic case
definition criteria to public health agencies in near-real time.
PMID- 28692392
TI - Evaluation of a Novel Syndromic Surveillance Query for Heat-Related Illness Using
Hospital Data From Maricopa County, Arizona, 2015.
AB - OBJECTIVES: We evaluated a novel syndromic surveillance query, developed by the
Council of State and Territorial Epidemiologists (CSTE) Heat Syndrome Workgroup,
for identifying heat-related illness cases in near real time, using emergency
department and inpatient hospital data from Maricopa County, Arizona, in 2015.
METHODS: The Maricopa County Department of Public Health applied 2 queries for
heat-related illness to area hospital data transmitted to the National Syndromic
Surveillance Program BioSense Platform: the BioSense "heat, excessive" query and
the novel CSTE query. We reviewed the line lists generated by each query and used
the diagnosis code and chief complaint text fields to find probable cases of heat
related illness. For each query, we calculated positive predictive values (PPVs)
for heat-related illness. RESULTS: The CSTE query identified 674 records, of
which 591 were categorized as probable heat-related illness, demonstrating a PPV
of 88% for heat-related illness. The BioSense query identified 791 patient
records, of which 589 were probable heat-related illness, demonstrating a PPV of
74% for heat-related illness. The PPV was substantially higher for the CSTE novel
and BioSense queries during the heat season (May 1 to September 30; 92% and 85%,
respectively) than during the cooler seasons (55% and 29%, respectively).
CONCLUSION: A novel query for heat-related illness that combined diagnosis codes,
chief complaint text terms, and exclusion criteria had a high PPV for heat
related illness, particularly during the heat season. Public health departments
can use this query to meet local needs; however, use of this novel query to
substantially improve public health heat-related illness prevention remains to be
seen.
PMID- 28692393
TI - Risk of Fall-Related Injury due to Adverse Weather Events, Philadelphia,
Pennsylvania, 2006-2011.
AB - OBJECTIVES: Following a surge in fall-related visits to local hospital emergency
departments (EDs) after a severe ice storm, the Philadelphia Department of Public
Health examined the association between inclement winter weather events and fall
related ED visits during a 5-year period. METHODS: Using a standardized set of
keywords, we identified fall-related injuries in ED chief complaint logs
submitted as part of Philadelphia Department of Public Health's syndromic
surveillance from December 2006 through March 2011. We compared days when falls
exceeded the winter fall threshold (ie, "high-fall days") with control days
within the same winter season. We then conducted matched case-control analysis to
identify weather and patient characteristics related to increased fall-related ED
visits. RESULTS: Fifteen high-fall days occurred during winter months in the 5
year period. In multivariable analysis, 18- to 64-year-olds were twice as likely
to receive ED care for fall-related injuries on high-fall days than on control
days. The crude odds of ED visits occurring from 7:00 am to 10:59 am were 70%
higher on high-fall days vs control days. Snow was a predictor of a high-fall
day: the adjusted odds of snow before a high-fall day as compared with snow
before a control day was 13.4. CONCLUSIONS: The association between the number of
fall-related ED visits and weather-related fall injuries, age, and timing
suggests that many events occurred en route to work in the morning. Promoting
work closures or delaying openings after severe winter weather would allow time
for better snow or ice removal, and including "fall risk" in winter weather
advisories might effectively warn morning commuters. Both strategies could help
reduce the number of weather-related fall injuries.
PMID- 28692394
TI - Using an Emergency Department Syndromic Surveillance System to Evaluate Reporting
of Potential Rabies Exposures, Illinois, 2013-2015.
AB - OBJECTIVES: Mandatory reporting of potential rabies exposures and initiation of
postexposure prophylaxis (PEP) allow local health authorities to monitor PEP
administration for errors. Our objectives were to use an emergency department
(ED) syndromic surveillance system to (1) estimate reporting compliance for
exposure to rabies in suburban Cook County, Illinois, and (2) initiate
interventions to improve reporting and reassess compliance. METHODS: We queried
ED records from 45 acute care hospitals in Cook County and surrounding areas from
January 1, 2013, through June 30, 2015, for chief complaints or discharge
diagnoses pertaining to rabies, PEP, or contact with a wild mammal (eg, bat,
raccoon, skunk, fox, or coyote). We matched patients with >=1 ED visit for
potential rabies exposure to people with potential rabies exposure reported to
the Cook County Department of Public Health. We considered nonmatches to have
unreported exposures. We then initiated active surveillance in July 2015,
disseminated education on reporting requirements in August and September 2015,
and reassessed reporting completeness from July 2015 through February 2016.
RESULTS: Of 248 patients with rabies-related ED visits from January 2013 through
June 2015, 63 (25.4%) were reported. After interventions were implemented to
increase reporting compliance, 53 of 98 (54.1%) patients with rabies-related ED
visits from July 2015 through February 2016 were reported. Patients with ED
visits for potential rabies exposure were twice as likely to be reported
postintervention than preintervention (risk ratio = 2.1; 95% CI, 1.6-2.8). The
volume of potential rabies exposure cases reported to the health department from
July 2015 through February 2016 increased by 252% versus the previous year.
CONCLUSIONS: Potential rabies exposures and PEP initiation are underreported in
suburban Cook County. ED syndromic surveillance records can be used to estimate
reporting compliance and conduct active surveillance.
PMID- 28692395
TI - A Practitioner-Driven Research Agenda for Syndromic Surveillance.
AB - Syndromic surveillance has expanded since 2001 in both scope and geographic reach
and has benefited from research studies adapted from numerous disciplines. The
practice of syndromic surveillance continues to evolve rapidly. The International
Society for Disease Surveillance solicited input from its global surveillance
network on key research questions, with the goal of improving syndromic
surveillance practice. A workgroup of syndromic surveillance subject matter
experts was convened from February to June 2016 to review and categorize the
proposed topics. The workgroup identified 12 topic areas in 4 syndromic
surveillance categories: informatics, analytics, systems research, and
communications. This article details the context of each topic and its
implications for public health. This research agenda can help catalyze the
research that public health practitioners identified as most important.
PMID- 28692396
TI - Characterizing the Effects of Extreme Cold Using Real-time Syndromic
Surveillance, Ontario, Canada, 2010-2016.
AB - Morbidity and mortality from exposure to extreme cold highlight the need for
meaningful temperature thresholds to activate public health alerts. We analyzed
emergency department (ED) records for cold temperature-related visits collected
by the Acute Care Enhanced Surveillance system-a syndromic surveillance system
that captures data on ED visits from hospitals in Ontario-for geographic trends
related to ambient winter temperature. We used 3 Early Aberration Reporting
System algorithms of increasing sensitivity-C1, C2, and C3-to determine the
temperature at which anomalous counts of cold temperature-related ED visits
occurred in northern and southern Ontario from 2010 to 2016. The C2 algorithm was
the most sensitive detection method. Results showed lower threshold temperatures
for Acute Care Enhanced Surveillance alerts in northern Ontario than in southern
Ontario. Public health alerts for cold temperature warnings that are based on
cold temperature-related ED visit counts and ambient temperature may improve the
accuracy of public warnings about cold temperature risks.
PMID- 28692397
TI - Using Syndromic Surveillance for All-Hazards Public Health Surveillance:
Successes, Challenges, and the Future.
PMID- 28692398
TI - Enhancing Surveillance for Mass Gatherings: The Role of Syndromic Surveillance.
PMID- 28692399
TI - Risk Assessment During the Pan American and Parapan American Games, Toronto,
2015.
AB - During the summer of 2015, the Pan American and Parapan American Games took place
in the Greater Toronto area of Ontario, Canada, bringing together thousands of
athletes and spectators from around the world. The Acute Care Enhanced
Surveillance (ACES) system-a syndromic surveillance system that captures
comprehensive hospital visit triage information from acute care hospitals across
Ontario-monitored distinct syndromes throughout the games. We describe the
creation and use of a risk assessment tool to evaluate alerts produced by ACES
during this period. During the games, ACES generated 1420 alerts, 4 of which were
considered a moderate risk and were communicated to surveillance partners for
further action. The risk assessment tool was useful for public health
professionals responsible for surveillance activities during the games. Next
steps include integrating the tool within the ACES system.
PMID- 28692400
TI - Developing Syndromic Surveillance to Monitor and Respond to Adverse Health Events
Related to Psychoactive Substance Use: Methods and Applications.
AB - INTRODUCTION: Recent increases in drug overdose deaths, both in New York City and
nationally, highlight the need for timely data on psychoactive drug-related
morbidity. We developed drug syndrome definitions for syndromic surveillance to
monitor drug-related emergency department (ED) visits in real time. MATERIALS AND
METHODS: We used 2012 archived syndromic surveillance data from New York City
hospitals to develop definitions for psychoactive drug-related syndromes. The
dataset contained ED visit-level information that included patients' chief
complaints, dates of visits, ZIP codes of residence, discharge diagnoses, and
dispositions. After manually reviewing chief complaints, we developed a
classification scheme comprising 3 categories (overdose, drug mention, and drug
abuse/misuse), which we used to define 25 psychoactive drug syndromes. From July
2013 through December 2015, the New York City Department of Health and Mental
Hygiene performed daily syndromic surveillance of psychoactive drug-related ED
visits using the 25 syndrome definitions. RESULTS: Syndromic surveillance
triggered 4 public health investigations, supported 8 other public health
investigations that had been triggered by other mechanisms, and resulted in the
identification of 5 psychoactive drug-related outbreaks. Syndromic surveillance
also identified a substantial increase in synthetic cannabinoid-related visits
(from an average of 3 per week in January 2014 to >300 per week in July 2015) and
an increase in heroin overdose visits (from 80 to 171 in the first 3 quarters of
2012 and 2014, respectively) in a single neighborhood. PRACTICE IMPLICATIONS:
Syndromic surveillance using these novel definitions enabled monitoring of trends
in psychoactive drug-related morbidity, initiation and support of public health
investigations, and targeting of interventions. Health departments can refine
these definitions for their jurisdictions using the described methods and
integrate them into existing syndromic surveillance systems.
PMID- 28692401
TI - Developing a Multidisciplinary Syndromic Surveillance Academic Research Program
in the United Kingdom: Benefits for Public Health Surveillance.
PMID- 28692402
TI - Enhanced Influenza Surveillance Using Telephone Triage and Electronic Syndromic
Surveillance in the Department of Veterans Affairs, 2011-2015.
AB - Telephone triage (TT) is a method whereby medical professionals speak by
telephone to patients to assess their symptoms or health concerns and offer
advice. These services are often administered through an electronic TT system,
which guides TT professionals during the encounter through the use of structured
protocols and algorithms to help determine the severity of the patients' health
issue and refer them to appropriate care. TT is also an emerging data source for
public health surveillance of infectious and noninfectious diseases, including
influenza. We calculated Spearman correlation coefficients to compare the weekly
number of US Department of Veterans Affairs (VA) TT calls with other conventional
influenza measures for the 2011-2012 through 2014-2015 influenza seasons, for
which there were a total of 35 666 influenza-coded TT encounters. Influenza-coded
calls were strongly correlated with weekly VA influenza-coded hospitalizations
(0.85), emergency department visits (0.90), influenza-like illness outpatient
visits (0.92), influenza tests performed (0.86), positive influenza tests (0.82),
and influenza antiviral prescriptions (0.89). The correlation between VA-TT and
Centers for Disease Control and Prevention (CDC) national data for weekly
influenza hospitalizations, influenza tests performed, and positive influenza
tests was also strong. TT correlates well with VA health care use and CDC data
and is a timely data source for monitoring influenza activity.
PMID- 28692403
TI - Accurate Region-of-Interest Recovery Improves the Measurement of the Cell
Migration Rate in the In Vitro Wound Healing Assay.
AB - The wound healing assay is widely used for the quantitative analysis of highly
regulated cellular events. In this essay, a wound is voluntarily produced on a
confluent cell monolayer, and then the rate of wound reduction (WR) is
characterized by processing images of the same regions of interest (ROIs)
recorded at different time intervals. In this method, sharp-image ROI recovery is
indispensable to compensate for displacements of the cell cultures due either to
the exploration of multiple sites of the same culture or to transfers from the
microscope stage to a cell incubator. ROI recovery is usually done manually and,
despite a low-magnification microscope objective is generally used (10x),
repositioning imperfections constitute a major source of errors detrimental to
the WR measurement accuracy. We address this ROI recovery issue by using
pseudoperiodic patterns fixed onto the cell culture dishes, allowing the easy
localization of ROIs and the accurate quantification of positioning errors. The
method is applied to a tumor-derived cell line, and the WR rates are measured by
means of two different image processing software. Sharp ROI recovery based on the
proposed method is found to improve significantly the accuracy of the WR
measurement and the positioning under the microscope.
PMID- 28692404
TI - One-step hot formamide extraction of RNA from Saccharomyces cerevisiae.
AB - Current methods for isolating RNA from budding yeast require lengthy and
laborious steps such as freezing and heating with phenol, homogenization with
glass beads, or enzymatic digestion of the cell wall. Here, extraction with a
solution of formamide and EDTA was adapted to isolate RNA from whole yeast cells
through a rapid and easily scalable procedure that does not require mechanical
cell lysis, phenol, or enzymes. RNA extracted with formamide-EDTA can be directly
loaded on gels for electrophoretic analysis without alcohol precipitation. A
simplified protocol for downstream DNase treatment and reverse transcription
reaction is also included. The formamide-EDTA extraction of yeast RNA is faster,
safer, and more economical than conventional methods, outperforms them in terms
of total yield, and greatly increases throughput.
PMID- 28692405
TI - 6S RNA in Rhodobacter sphaeroides: 6S RNA and pRNA transcript levels peak in late
exponential phase and gene deletion causes a high salt stress phenotype.
AB - The function of 6S RNA, a global regulator of transcription, was studied in the
photosynthetic alpha-proteobacterium Rhodobacter sphaeroides. The cellular levels
of R. sphaeroides 6S RNA peak toward the transition to stationary phase and
strongly decrease during extended stationary phase. The synthesis of so-called
product RNA transcripts (mainly 12-16-mers) on 6S RNA as template by RNA
polymerase was found to be highest in late exponential phase. Product RNA >= 13
mers are expected to trigger the dissociation of 6S RNA:RNA polymerase complexes.
A 6S RNA deletion in R. sphaeroides had no impact on growth under various
metabolic and oxidative stress conditions (with the possible exception of tert
butyl hydroperoxide stress). However, the 6S RNA knockout resulted in a robust
growth defect under high salt stress (0.25 M NaCl). Remarkably, the sspA gene
encoding the putative salt stress-induced membrane protein SspA and located
immediately downstream of the 6S RNA (ssrS) gene on the antisense strand was
expressed at elevated levels in the DeltassrS strain when grown in the presence
of 250 mM NaCl.
PMID- 28692406
TI - Mortality from Circulatory Diseases and other Non-Cancer Outcomes among Nuclear
Workers in France, the United Kingdom and the United States (INWORKS).
AB - Positive associations between external radiation dose and non-cancer mortality
have been found in a number of published studies, primarily of populations
exposed to high-dose, high-dose-rate ionizing radiation. The goal of this study
was to determine whether external radiation dose was associated with non-cancer
mortality in a large pooled cohort of nuclear workers exposed to low-dose
radiation accumulated at low dose rates. The cohort comprised 308,297 workers
from France, United Kingdom and United States. The average cumulative equivalent
dose at a tissue depth of 10 mm [Hp(10)] was 25.2 mSv. In total, 22% of the
cohort were deceased by the end of follow-up, with 46,029 deaths attributed to
non-cancer outcomes, including 27,848 deaths attributed to circulatory diseases.
Poisson regression was used to investigate the relationship between cumulative
radiation dose and non-cancer mortality rates. A statistically significant
association between radiation dose and all non-cancer causes of death was
observed [excess relative risk per sievert (ERR/Sv) = 0.19; 90% CI: 0.07, 0.30].
This was largely driven by the association between radiation dose and mortality
due to circulatory diseases (ERR/Sv = 0.22; 90% CI: 0.08, 0.37), with slightly
smaller positive, but nonsignificant, point estimates for mortality due to
nonmalignant respiratory disease (ERR/Sv = 0.13; 90% CI: -0.17, 0.47) and
digestive disease (ERR/Sv = 0.11; 90% CI: -0.36, 0.69). The point estimate for
the association between radiation dose and deaths due to external causes of death
was nonsignificantly negative (ERR = -0.12; 90% CI: <-0.60, 0.45). Within
circulatory disease subtypes, associations with dose were observed for mortality
due to cerebrovascular disease (ERR/Sv = 0.50; 90% CI: 0.12, 0.94) and mortality
due to ischemic heart disease (ERR/Sv = 0.18; 90% CI: 0.004, 0.36). The estimates
of associations between radiation dose and non-cancer mortality are generally
consistent with those observed in atomic bomb survivor studies. The findings of
this study could be interpreted as providing further evidence that non-cancer
disease risks may be increased by external radiation exposure, particularly for
ischemic heart disease and cerebrovascular disease. However, heterogeneity in the
estimated ERR/Sv was observed, which warrants further investigation. Further
follow-up of these cohorts, with the inclusion of internal exposure information
and other potential confounders associated with lifestyle factors, may prove
informative, as will further work on elucidating the biological mechanisms that
might cause these non-cancer effects at low doses.
PMID- 28692407
TI - Overdose history is associated with postdetoxification treatment preference for
persons with opioid use disorder.
AB - BACKGROUND: Without aftercare treatment, persons discharged from short-term
inpatient detoxification for opioid use disorder are at high risk of relapse. In
previous work, those who were recently homeless or had pending legal problems
were more likely to prefer residential treatment for aftercare. Here, based on
clinical experience, the authors hypothesize that a particular clinical factor,
surviving an opioid overdose, will be associated with aftercare preference.
METHODS: Between May and December 2015, the authors surveyed consecutive persons
seeking inpatient opioid detoxification. To assess aftercare treatment
preference, participants were asked, "If you had unlimited treatment options and
all were free, which one would work best for you when you leave here?" To assess
overdose history, participants were asked about overdose "since your first drug
use," and "in the last year." RESULTS: Participants' (N = 440) mean age was 32.3
(+/- 8.7) years; 70.7% were male. More than half (51.1%) of participants
expressed an aftercare preference for medication-assisted treatment (MAT), 12.7%
for outpatient counseling only, 10.7% for residential treatment,18.6% for no
formal treatment (Narcotics Anonymous/Alcoholics Anonymous only or a halfway
house), and 6.8% did not want any postdetoxification treatment. About 40%
reported a history of overdose, and 24.8% reported past year overdose. In the
multivariate model, treatment preference was associated with sex (P < .001),
homelessness (P = .01), and history of drug overdose (P = .02). CONCLUSIONS:
Although MAT was preferred by the majority of participants, the experience of a
nonfatal overdose was associated with the choice of residential treatment as
postdetoxification treatment.
PMID- 28692408
TI - Preliminary findings of altered functional connectivity of the default mode
network linked to functional outcomes one year after pediatric traumatic brain
injury.
AB - PURPOSE AND METHOD: This study examined functional connectivity of the default
mode network (DMN) and examined brain-behavior relationships in a pilot cohort of
children with chronic mild to moderate traumatic brain injury (TBI). RESULTS:
Compared to uninjured peers, children with TBI demonstrated less anti-correlated
functional connectivity between DMN and right Brodmann Area 40 (BA 40). In
children with TBI, more anomalous less anti-correlated) connectivity between DMN
and right BA 40 was linked to poorer performance on response inhibition tasks.
CONCLUSION: Collectively, these preliminary findings suggest that functional
connectivity between DMN and BA 40 may relate to longterm functional outcomes in
chronic pediatric TBI.
PMID- 28692410
TI - One Health Innovations Research Symposium: Preventing the Next Pandemic
Conference August 27-28, 2017 Kansas City Convention Center, Kansas City, MO.
PMID- 28692411
TI - Evaluation of the Health Benefits of a Multivitamin, Multimineral, Herbal,
Essential Oil-Infused Supplement: A Pilot Trial.
AB - This study was designed to quantitatively evaluate the health benefits of a
multivitamin, multimineral, herbal, essential oil-infused supplement using serum
biomarkers. We also qualitatively evaluated the health effects of this supplement
using a survey. Sixteen participants were recruited to take the supplement as
directed for two months. The levels of the following serum components were
measured in the participants: total cholesterol, high-density lipoprotein (HDL)
cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides,
lipoprotein(a), LDL/HDL cholesterol ratio, total/HDL cholesterol ratio, ferritin,
fibrinogen, C-reactive protein, insulin, testosterone, sex hormone binding
globulin, free androgen index, red blood cell magnesium, homocysteine, coenzyme
Q10, lipid peroxides, alpha-tocopherol, gamma-tocopherol, cardiovascular index,
eicosapentaenoic acid (EPA), arachidonic acid (AA), and the AA/EPA ratio. The
following markers were significantly improved (p <.05) after two months of
supplementation: HDL cholesterol, LDL/HDL cholesterol ratio, fasting insulin,
homocysteine, serum vitamin E, EPA, and the AA/EPA ratio. These findings
demonstrate that the supplementation had significant positive effects on
biochemical indicators of cardiovascular health, antioxidant status,
inflammation, and blood glucose regulation. All of the outcomes in the 16-item
qualitative survey were improved after two months of supplementation. Twelve of
these outcomes were significantly improved. The participants reported more mental
clarity, energy, motivation, control, balance, and happiness, while reporting
less back pain, muscle pain, cold and flu incidence, anxiety, frustration, and
irritation at the end of the two-month supplementation period. Although definite
clinical efficacy remains elusive, these results suggest that the supplement may
provide a broad range of health benefits for users in a short period.
PMID- 28692412
TI - Plant Sterol Esters in Extruded Food Model Inhibits Colon Carcinogenesis by
Suppressing Inflammation and Stimulating Apoptosis.
AB - Plant sterols in their free forms are known to inhibit colon cancer. Whether
these activities persist when compounds are incorporated into processed food is
not reported yet. This study aimed to test the ability of plant sterol esters
(PSE) incorporated into a nonpuffed extruded food (NPE) model to inhibit colon
carcinogenesis. PSE was added into NPE at four concentrations (0.0%, 0.7%, 1.4%,
and 2.1%). PSE-NPE activity was tested in azoxymethane/dextran sodium sulfate
induced Balb/c mice. The groups given PSE-NPE did not show any colon tumor
formation. Immunohistochemistry results revealed that the group fed with 1.4% PSE
had the lowest histoscore for cyclooxygenase-2 expression and the highest
histoscore for cleaved caspase-3, cleaved caspase-8, and cleaved caspase
9expressions. The results of this study indicated that even after incorporation
into a food system, which is processed using high pressure and temperature, PSE
retained its chemopreventive activity. The proposed mechanisms are by suppressing
inflammation and inducing apoptosis.
PMID- 28692413
TI - Effects of Astaxanthin on Liver and Leukocyte Parameters in Healthy Climacteric
Women: Preliminary Data.
PMID- 28692414
TI - How common is within-plant signaling via volatiles?
AB - Many plants respond to herbivory by releasing a complex blend of volatiles that
may differ from that emitted by intact counterparts. These herbivore-induced
plant volatiles (HIPV) mediate many interactions among plants and their community
members, including alerting undamaged leaves of the attacked or neighboring
plants to impending danger. It has been postulated that HIPVs evolved for within
plant signaling and that other organisms subsequently evolved to use them.
However, only 7 studies have reported HIPV-mediated within-plant signaling, most
conducted in the laboratory or greenhouse. This leaves open the ecological
relevance and evolutionary underpinning of the phenomenon. We recently observed
within-plant signaling in hybrid aspen under laboratory and field conditions.
Greenhouse experiments showed that HIPVs mediated the process. While our study
adds an aspen hybrid to the list of plants in which within-plant signaling has
been demonstrated, we lack understanding of how common the process is and whether
plants obtain fitness benefits.
PMID- 28692415
TI - Whole Genome Sequencing of Mycobacterium tuberculosis Isolates From
Extrapulmonary Sites.
AB - Tuberculosis (TB) remains one of the leading causes of morbidity and mortality
worldwide. Extrapulmonary tuberculosis (EPTB) constitutes around 15-20% of TB
cases in immunocompetent individuals. Extrapulmonary sites that are affected by
TB include bones, lymph nodes, meningitis, pleura, and genitourinary tract. Whole
genome sequencing has emerged as a powerful tool to map genetic diversity among
Mycobacterium tuberculosis (MTB) isolates and identify the genomic signatures
associated with drug resistance, pathogenesis, and disease transmission. Several
pulmonary isolates of MTB have been sequenced over the years. However,
availability of whole genome sequences of MTB isolates from extrapulmonary sites
is limited. Some studies suggest that genetic variations in MTB might contribute
to disease presentation in extrapulmonary sites. This can be addressed if whole
genome sequence data from large number of extrapulmonary isolates becomes
available. In this study, we have performed whole genome sequencing of five MTB
clinical isolates derived from EPTB sites using next-generation sequencing
platform. We identified 1434 nonsynonymous single nucleotide variations (SNVs),
143 insertions and 105 deletions. This includes 279 SNVs that were not reported
before in publicly available datasets. We found several mutations that are known
to confer resistance to drugs. All the five isolates belonged to East-African
Indian lineage (lineage 3). We identified 9 putative prophage DNA integrations
and 14 predicted clustered regularly interspaced short palindromic repeats
(CRISPR) in MTB genome. Our analysis indicates that more work is needed to map
the genetic diversity of MTB. Whole genome sequencing in conjunction with
comprehensive drug susceptibility testing can reveal clinically relevant
mutations associated with drug resistance.
PMID- 28692416
TI - Immunoglobulin G N-Glycans as Potential Postgenomic Biomarkers for Hypertension
in the Kazakh Population.
AB - Next-generation (postgenomic) biomarkers from the nascent field of glycomics now
offer fresh vistas for innovation in chronic disease biomarkers and system
diagnostics in clinical medicine. Our previous work has shown an association
between hypertension and immunoglobulin G (IgG) glycome composition, suggesting
that individual variation in N-glycosylation of IgG might contribute to
hypertension pathogenesis. The present study examined, for the first time to the
best of our knowledge, the IgG N-glycans as potential biomarkers for hypertension
in the Kazakh population. The profile of 60 N-glycopeptides of IgG subclass
isolated from plasma samples of 150 Kazakh study participants was analyzed by
nano ultra-performance liquid chromatography with mass spectrometry. Fourteen IgG
subclass-specific Fc N-glycopeptide structures, along with one derived
glycosylation trait in subclasses IgG2/3 and IgG4, were found to correlate with
systolic blood pressure and/or diastolic blood pressure. For differentiation of
hypertension and healthy status in the Kazakh population sample, the receiver
operating characteristic curve analysis showed that the performance of the model,
including nine IgG N-glycans, was greater than the traditional gender, age, and
body mass index based model (p < 0.05). This study indicates that alteration in
Fc N-glycopeptide profiles of plasma IgG subclasses is associated with blood
pressure status in the Kazakh population. IgG N-glycosylation profiles may serve
as potential biomarkers for hypertension in the Kazakhs, thus contributing to
move toward personalized medicine. Further studies of postgenomic glycomic
biomarkers in cardiovascular and chronic diseases are timely and called for.
PMID- 28692417
TI - Hypothesis: Are There Molecular Signatures of Yoga Practice in Peripheral Blood
Mononuclear Cells?
PMID- 28692418
TI - Contribution of Genetic Polymorphisms and Haplotypes in DRD2, BDNF, and Opioid
Receptors to Heroin Dependence and Endophenotypes Among the Han Chinese.
AB - Heroin and drug dependence are major contributors to global health burden
worldwide, but their underlying mechanisms remain elusive and may vary from
population to population. Reward- and memory-related candidate genes dopamine D2
receptor (DRD2) and brain-derived neurotrophic factor (BDNF), as well as the
opioid receptor genes (OPRM1, OPRD1, and OPRK1), have been implicated in drug
dependence, but relatively little is known on their contributions to heroin
dependence in populations worldwide. Hence, we evaluated the contributions of the
above five candidate genes in heroin dependence and several important related
endophenotypes (the onset age of heroin use and subjective response to first
heroin use), at single single-nucleotide polymorphism as well as haplotype
levels, in a Han Chinese population sample. We genotyped 546 unrelated and heroin
dependent subjects for the candidate genes noted, and 228 sex- and age-matched
unrelated controls. The G allele of rs4654327 (OPRD1), DRD2 haplotype block
CCGCCGTT (rs6277-rs1076560-rs2283265-rs2734833-rs2075652-rs1079596-rs4436578
rs11214607), and OPRD1 haplotypes TACG (rs6669447-rs2236857-rs508448-rs4654327),
CG (rs508448-rs4654327), and TG (rs6669447-rs4654327) were significantly
associated with heroin dependence phenotype. Homozygotes AA at rs6265 (BDNF), TT
at rs16917234 (BDNF), and CC at rs508448 (OPRD1) also appeared as risk factors
for the endophenotype earlier age of onset for heroin use. Two OPRM1 haplotypes,
AG (rs1799971-rs1381376) and AT (rs1799971-rs3778151), were observed as potential
protective factors. These emerging findings contribute to the literature on
genetic biomarkers of drug dependence and related endophenotypes, and call for
replication in independent population.
PMID- 28692420
TI - Use of a Smartphone Recovery Tool for Latinos with Co-Occurring Alcohol and Other
Drug Disorders and Mental Disorders.
AB - OBJECTIVE: Addressing alcohol and other drug disorders and other mental disorders
among adult Hispanics/Latinos is of critical concern, as they are one of the
fastest-growing ethnic groups with a disproportionate rate of disease, mental
disorders, and poverty. Although improvement in outcomes is associated with
sustained participation in ongoing treatment for co-occurring alcohol and other
drug disorders/mental disorders, continuing care is rare for these chronic
conditions, especially for Latinos with more limited access to culturally and
linguistically competent services. METHODS: The evidence-based smartphone
recovery application Addiction-Comprehensive Health Enhancement Support System (A
CHESS) was translated and adapted for Spanish-speaking Latinos with alcohol and
other drug disorders/mental disorders, thus developing CASA-CHESS to address a
high level of need for services, high rates of relapse, and lack of existing
culturally competent services for Latinos. RESULTS: Of the 79 Latino clients who
completed residential treatment and received a smartphone equipped with CASA
CHESS, 26.6% discontinued using CASA-CHESS and 73.4% remained active for four or
more months. CASA-CHESS usage was sustained over the four months across all three
tenets of self-determination theory (competence, relatedness, and autonomy), with
the most commonly utilized services being relevant to relatedness (e.g.,
messaging, discussion boards). CASA-CHESS clients demonstrated a similar pattern
of usage to A-CHESS clients. CONCLUSIONS: Findings illustrate that Spanish
speaking Latinos with alcohol and other drug disorders/mental disorders will use
a smartphone application to assist with their recovery, continuing their access
to resources, case management, and quality information after leaving residential
treatment. Consistent with previous findings, our results also emphasize the
importance of social support during the four months post-discharge. Such evidence
based, theory-driven digital interventions may extend access to culturally and
linguistically competent services.
PMID- 28692421
TI - Auto-regulation in the powerhouse.
AB - Mitochondrial flashes have a central role in ensuring that ATP levels remain
constant in heart cells.
PMID- 28692419
TI - Long-Term Cigarette Smoke Exposure and Changes in MiRNA Expression and Proteome
in Non-Small-Cell Lung Cancer.
AB - Chronic exposure to cigarette smoke markedly increases the risk for lung cancer.
Regulation of gene expression at the post-transcriptional level by miRNAs
influences a variety of cancer-related interactomes. Yet, relatively little is
known on the effects of long-term cigarette smoke exposure on miRNA expression
and gene regulation. NCI-H292 (H292) is a cell line sensitive to cigarette smoke
with mucoepidermoid characteristics in culture. We report, in this study,
original observations on long-term (12 months) cigarette smoke effects in the
H292 cell line, using microarray-based miRNA expression profiling, and stable
isotopic labeling with amino acids in cell culture-based quantitative proteomic
analysis. We identified 112 upregulated and 147 downregulated miRNAs (by twofold)
in cigarette smoke-treated H292 cells. The liquid chromatography-tandem mass
spectrometry analysis identified 3,959 proteins, of which, 303 proteins were
overexpressed and 112 proteins downregulated (by twofold). We observed 39 miRNA
target pairs (proven targets) that were differentially expressed in response to
chronic cigarette smoke exposure. Gene ontology analysis of the target proteins
revealed enrichment of proteins in biological processes driving metabolism, cell
communication, and nucleic acid metabolism. Pathway analysis revealed the
enrichment of phagosome maturation, antigen presentation pathway, nuclear factor
erythroid 2-related factor 2-mediated oxidative stress response, and cholesterol
biosynthesis pathways in cigarette smoke-exposed cells. In conclusion, this
report makes an important contribution to knowledge on molecular changes in a
lung cell line in response to long term cigarette smoke exposure. The findings
might inform future strategies for drug target, biomarker and diagnostics
innovation in lung cancer, and clinical oncology. These observations also call
for further research on the extent to which continuing or stopping cigarette
smoking in patients diagnosed with lung cancer translates into molecular and
clinical outcomes.
PMID- 28692424
TI - Expert Recommendations for the Use of Hypochlorous Solution: Science and Clinical
Application.
AB - Wound complications such as infection continue to in ict enormous nancial and
patient quality-of-life burdens.The traditional practice of using antiseptics and
antibiotics to prevent and/or treat infections has been questioned with
increasing concerns about the cytoxitity of antiseptics and proliferation of
antibiotic resistant bacteria. Solutions of sodium hypochlorite (NaOCl), commonly
known as Dakin's solution, have been used in wound care for 100 years. In the
last 15 years, more advanced hypochlorous acid (HOCl) solutions, based on
electrochemistry, have emerged as safe and viable wound-cleansing agents and
infection treatment adjunct therapies. After developing a literature-based
summary of available evidence, a consensus panel of wound care researchers and
practitioners met to review the evidence for 1) the antimicrobial effectiveness
of HOCl based on in vitro studies, 2) the safety of HOCl solutions, and 3) the
effectiveness of HOCl acid in treating different types of infected wounds in
various settings and to develop recommendations for its use and application to
prevent wound infection and treat infected wounds in the context of accepted
wound care algorithms. Each participant gave a short presentation; this was
followed by a moderated roundtable discussion with consensus-making regarding
conclusions. Based on in vitro studies, the antimicrobial activity of HOCl
appears to be comparable to other antiseptics but without cytotoxicity; there is
more clinical evidence about its safety and effectiveness. With regard to the
resolution of infection and improvement in wound healing by adjunct HOCl use,
strong evidence was found for use in diabetic foot wounds; moderate evidence for
use in septic surgical wounds; low evidence for venous leg ulcers, wounds of
mixed etiology, or chronic wounds; and no evidence for burn wounds.The panel
recommended HOCl should be used in addition to tissue management, infection,
moisture imbalance, edge of the wound (the TIME algorithm) and aggressive
debridement.The panel also recommended intralesional use of HOCl or other methods
that ensure the wound is covered with the solution for 15 minutes after
debridement. More controlled clinical studies are needed to determine the safety
and ef cacy of HOCl in wound types with limited outcomes data and to evaluate
outcomes of various application methods.
PMID- 28692422
TI - Mitochondrial flashes regulate ATP homeostasis in the heart.
AB - The maintenance of a constant ATP level ('set-point') is a vital homeostatic
function shared by eukaryotic cells. In particular, mammalian myocardium
exquisitely safeguards its ATP set-point despite 10-fold fluctuations in cardiac
workload. However, the exact mechanisms underlying this regulation of ATP
homeostasis remain elusive. Here we show mitochondrial flashes (mitoflashes),
recently discovered dynamic activity of mitochondria, play an essential role for
the auto-regulation of ATP set-point in the heart. Specifically, mitoflashes
negatively regulate ATP production in isolated respiring mitochondria and, their
activity waxes and wanes to counteract the ATP supply-demand imbalance caused by
superfluous substrate and altered workload in cardiomyocytes. Moreover,
manipulating mitoflash activity is sufficient to inversely shift the otherwise
stable ATP set-point. Mechanistically, the Bcl-xL-regulated proton leakage
through F1Fo-ATP synthase appears to mediate the coupling between mitoflash
production and ATP set-point regulation. These findings indicate mitoflashes
appear to constitute a digital auto-regulator for ATP homeostasis in the heart.
PMID- 28692425
TI - Perceptions of medical graduates and their workplace supervisors towards a
medical school clinical audit program.
AB - Objectives: This study explores how medical graduates and their workplace
supervisors perceive the value of a structured clinical audit program (CAP)
undertaken during medical school. Methods: Medical students at the University of
Notre Dame Fremantle complete a structured clinical audit program in their final
year of medical school. Semi-structured interviews were conducted with 12 Notre
Dame graduates (who had all completed the CAP), and seven workplace supervisors
(quality and safety staff and clinical supervisors). Purposeful sampling was
used to recruit participants and data were analysed using thematic analysis.
Results: Both graduates and workplace supervisors perceived the CAP to be
valuable. A major theme was that the CAP made a contribution to individual
graduate's medical practice, including improved knowledge in some areas of
patient care as well as awareness of healthcare systems issues and preparedness
to undertake scientifically rigorous quality improvement activities. Graduates
perceived that as a result of the CAP, they were confident in undertaking a
clinical audit after graduation. Workplace supervisors perceived the value of
the CAP beyond an educational experience and felt that the audits undertaken by
students improved quality and safety of patient care. Conclusions: It is vital
that health professionals, including medical graduates, be able to carry out
quality and safety activities in the workplace. This study provides evidence that
completing a structured clinical audit during medical school prepares graduates
to undertake quality and safety activities upon workplace entry. Other health
professional faculties may be interested in incorporating a similar program in
their curricula.
PMID- 28692426
TI - Single crystalline ZnO radial homojunction light-emitting diodes fabricated by
metalorganic chemical vapour deposition.
AB - ZnO radial p-n junction architecture has the potential for forward-leap of light
emitting diode (LED) technology in terms of higher efficacy and economical
production. We report on ZnO radial p-n junction-based light emitting diodes
prepared by full metalorganic chemical vapour deposition (MOCVD) with hydrogen
assisted p-type doping approach. The p-type ZnO(P) thin films were prepared by
MOCVD with the precursors of dimethylzinc, tert-butanol, and
tertiarybutylphosphine. Controlling the precursor flow for dopant results in the
systematic change of doping concentration, Hall mobility, and electrical
conductivity. Moreover, the approach of hydrogen-assisted phosphorous doping in
ZnO expands the understanding of doping behaviour in ZnO. Ultraviolet and visible
electroluminescence of ZnO radial p-n junction was demonstrated through a
combination of position-controlled nano/microwire and crystalline p-type ZnO(P)
radial shell growth on the wires. The reported research opens a pathway of
realisation of production-compatible ZnO p-n junction LEDs.
PMID- 28692427
TI - Isotropic shrinkage of the oxygen octahedron in SrTiO3 under uniaxial pressure.
AB - X-ray absorption spectra at the Ti K-edge of a SrTiO3 single crystal under
uniaxial pressure were measured to obtain evidence of uniaxial pressure-induced
polarization predicted in SrTiO3 from the electronic viewpoint. The pre-edge 3d-e
g peak decreases in intensity with increasing uniaxial pressure, together with an
energy shift to higher energy side. Contrary to uniaxial deformation, these
changes were independent of incident x-ray polarization. This implies the
presence of a mechanism that maintains the isotropic coordination environment
around a Ti atom, i.e. a tilt and rotation of the TiO6 octahedron accompanied by
its isotropic shrinkage, hence the local polarization essential to the
ferroelectric order cannot be observed.
PMID- 28692428
TI - Electronic and magnetic properties of low-dimensional system Co2TeO3Cl2.
AB - The electronic and magnetic properties of transition metal oxyhalide compound
Co2TeO3Cl2 are investigated using first principle calculations within the
framework of density functional theory. To find the underlying spin-lattice of
this compound, various hopping integrals and exchange interactions are
calculated. The calculations reveal that the dominant inter-chain and intra-chain
interactions are in the ab plane. The exchange path is visualized by Wannier
function plotting. The nearest neighbor and next nearest neighbor exchange
interactions are antiferromagnetic, making the system frustrated in low
dimension. Calculations are also done with spin-orbit coupling (SOC) to find out
the effect of SOC on this compound. Calculation of magnetocrystalline anisotropy
suggests that the easy axis is along the crystallographic b direction.
PMID- 28692429
TI - Synthetic cannabinoids: the hidden side of Spice drugs.
AB - Spice drugs are herbal mixtures sprayed with synthetic cannabinoids designed to
mimic the psychoactive ingredient in marijuana [Delta-tetrahydrocannabinol (Delta
THC)] and synthesized by introducing modifications to the chemical structure of
parental compounds aiming to circumvent legal regulations. Synthetic cannabinoid
use/abuse can be devastating as toxicological effects and adverse reactions
cannot be entirely predicted and may vary with the dose, route of administration,
individual vulnerability and concomitant intake with other drugs. The absence of
validated testing procedures in the clinical field makes difficult the adoption
of a therapeutic approach effective in coping with the synthetic cannabinoid
phenomenon, posing a significant challenge for prevention, treatment and public
health in general. The aim of this review is to gain insights into the
epidemiological, pharmacological and toxicological properties of synthetic
cannabinoids, aiming to provide a reliable background needed for the management
of synthetic cannabinoid-related adverse effects. Consumers, competent
authorities and medical care professionals should be aware of the risks
associated with synthetic cannabinoid use.
PMID- 28692430
TI - Adherence to Safe Sleep Recommendations by Families With Higher-order Multiples.
AB - BACKGROUND: More than 95% of higher-order multiples are born preterm and more
than 90% are low birth weight, making this group of infants especially vulnerable
to sudden infant death syndrome (SIDS). Emerging evidence suggests that families
with twins face challenges adhering to the American Academy of Pediatrics (AAP)
recommendations to reduce SIDS risks. Adherence to the AAP recommendations in
families with higher-order multiples has not been described. PURPOSE: This study
describes SIDS risk reduction infant care practices for higher-order multiples
during the first year of life. METHODS: Mothers caring for higher-order multiple
birth infants were recruited from an online support group. An online survey was
used to assess infant care practices when the infants were first brought home
from the hospital as well as at the time of the survey. RESULTS: Ten mothers of
triplets and 4 mothers of quadruplets responded. Less than 80% of the mothers
practiced "back to sleep" immediately postdischarge. Supine sleep positioning
decreased over time, particularly during daytime naps. Only 50% of the infants
shared the parents' bedroom and approximately 30% bed-shared with their siblings.
Sleep-time pacifier use was low. IMPLICATIONS FOR PRACTICE: Safe sleep education
must include specific questions regarding home sleeping arrangements,
encouragement of breast milk feedings, supine positioning, and pacifier use at
every sleep for higher-order multiple infants well before discharge in order for
parents to plan a safe sleep environment at home. IMPLICATIONS FOR RESEARCH:
Prospective studies to identify barriers and facilitators can inform future
strategies supporting adherence to safe sleep practices for higher-order multiple
infants.
PMID- 28692431
TI - Differing mechanisms of thrombin generation in live haematological and solid
cancer cells determined by calibrated automated thrombography.
AB - : Calibrated automated thrombography (CAT) is emerging as a reliable tool for
real-time estimation of thrombin generation potential. There is a clinical need
for knowledge about the pathways underlying the thrombotic phenotype of different
malignancies. Cells from solid (e.g. pancreatic cancer; n = 7) and malignant
haematological cell lines (e.g. multiple myeloma; n = 5) were evaluated for
thrombin generation, using CAT, with the addition of control plasma (NormTrol;
Helena Biosciences, Gateshead, UK)) or plasma deficient in coagulation factors
VII and XII. In addition, tissue factor (TF) cell surface expression was
determined by flow cytometry. In platelet-free plasma, thrombin generation in all
cancer cell lines was cell concentration dependent, with the pancreatic cancer
line CFPAC-1 producing the highest thrombin of 220 nmol/l at 5 * 10-cells/ml
concentration. Lag times and times to peak reflected most significant differences
out of all thrombin generation parameters measured and were inversely correlated
with cell surface TF surface expression. Solid tumour cell lines had higher
thrombin peaks, faster lag times, and a thrombin generation profile of overall
greater magnitude than haematological cell lines. In the absence of factor VII in
platelet-free plasma, thrombin generation in solid pancreatic cancer cell lines
was significantly reduced unlike in haematological cell lines. However, in the
absence of factor XII, thrombin generation was reduced more in haematological
cells but had little or no effect on solid cell lines. The CAT assay identified
characteristic differences in thrombin generation kinetics between solid tumour
and haematological cancer cell lines, of which lag time and time to peak
correlated with TF cell surface expression.
PMID- 28692432
TI - Telenursing Intervention for Clean Intermittent Urinary Catheterization Patients:
A Pilot Study.
AB - Telenursing is a promising strategy to make nursing care feasible in different
health situations, mainly to help patients with chronic illnesses. The aim in
this study was to test the feasibility (acceptability and usability) of a
telenursing intervention in care delivery to patients using clean intermittent
urinary catheterization. This descriptive study focused on an intervention
involving urology outpatients. The telenursing intervention was implemented
synchronously by audio calls and chat and asynchronously by e-mail as part of a
pilot study. The contact between nurse and patient was undertaken through an
active search or on spontaneous demand, in which the patient contacted the nurse
when necessary. During the 5 weeks of study, 21 telenursing care sessions took
place, including 13 (61.9%) on spontaneous demand and eight (38.1%) on active
demand. With regard to the technological resource used, 13 telenursing sessions
(61.9%) took place by telephone call and eight (30.1%) by e-mail. The pilot study
demonstrated the potential of the telenursing intervention to achieve important
results, and as a complement to the patients' traditional health treatment. In
addition, it revealed various barriers that need to be overcome for this type of
care to take place effectively.
PMID- 28692433
TI - A Nursing Pain Assessment and Record Information System: Design and Application
in the Oncology Department.
AB - Pain is an unpleasant sensory and emotional feeling accompanying existing,
impending, or potential tissue damage. Valid pain assessment and standardized
pain documentation are important in oncology pain management; however, they are
still deficient. Thus, we developed a pain assessment and record information
system for nurses in the oncology department and implemented a questionnaire
survey to evaluate users' acceptance of the system. The pain assessment system
focused on usability and efficiency to provide a modified workflow that was safe,
less time-consuming, patient centered, enjoyable, and efficient. The pain
assessment and record chart types in the system enabled greater standardization
of pain assessments and records. The application of the system greatly improved
the efficiency of nursing in the oncology department, guiding nurses in an
accurate and comprehensive patient pain assessment and contributing significantly
to further improvement in pain care standards and care decisions. Nurses and
doctors surveyed reported a high degree of satisfaction with factors such as
saving time and improving the capacity of pain control, suggesting that the
system enhanced the quality of pain management. Through this system, we can
promote pain management, improving care quality for patients.
PMID- 28692434
TI - Assessing Intensity of Nursing Care Needs Using Electronically Available Data.
AB - Although previous research has confirmed that nurse staffing affects patient
outcomes, some potentially important factors have not been accounted for in tools
to assess relationships between staffing and outcomes. The aim of this project
was to develop and test a Nursing Intensity of Care Index using electronically
available data from 152 072 patient discharges from three hospitals. Initially,
1765 procedure codes were reviewed; 69 were confirmed as directly increasing
nursing workload by at least 15 minutes per shift. Two research staff
independently reviewed a random sample of 5 patient days to assess interrater
reliability with complete scoring agreement. To assess face validity, eight nurse
clinician experts reviewed factors included in the Nursing Intensity of Care
Index to assess the accuracy of the nursing time estimates in the tool. To
examine concurrent validity, Nursing Intensity of Care Index scores for a random
sample of 28 patients from four clinical units were compared with assessments
made by a unit-based clinical nurse (low/medium/high intensity) for the same
patients on the same day with a Spearman correlation of 0.94. In preliminary
testing, data for the Nursing Intensity of Care Index, which accurately reflect
nursing care intensity, can be obtained electronically in real time. The next
steps will be a discrete-event simulation model and large-scale field trials.
PMID- 28692435
TI - Prim-O-glucosylcimifugin induces cell cycle arrest and apoptosis in acute
lymphoblastic leukemia cells.
AB - Prim-O-glucosylcimifugin is a major constituent in Radix Saposhnikovia that has
been long used for the treatment of pyrexia, rheumatism, and cancer in
traditional Chinese medicine. However, the molecular and cellular mechanisms
remain unknown regarding the therapeutic effect of prim-O-lucosylcimifugin. Here,
we investigated the effects of prim-O-glucosylcimifugin on cell cycle progression
and apoptosis in human acute lymphoblastic leukemia cells. Prim-O
glucosylcimifugin treatment resulted in marked increases in cell apoptosis and
cell cycle arrest at the G2/M phase. Mechanistically, prim-O-glucosylcimifugin
induced the degradation of beta-tubulin and downregulated phosphorylated CDK1
levels, a molecular indicator in the G2/M cell cycle arrest. Furthermore,
activation of caspase-3, caspase-8, and caspase-9 was involved in the prim-O
glucosylcimifugin-induced apoptosis. Our study reveals the anticancer activity of
prim-O-glucosylcimifugin and the potential underlying mechanisms.
PMID- 28692436
TI - Andrographolide enhances cisplatin-mediated anticancer effects in lung cancer
cells through blockade of autophagy.
AB - Lung cancer is the most common cause of cancer-related death worldwide and the
platinum-based drugs such as cisplatin have been used as the first line of the
treatment. However, the clinical effectiveness of such chemotherapy is limited by
intrinsic or acquired resistance. In this study, we found that cisplatin induced
autophagy that attenuated the sensitivity of both A549 and Lewis lung cancer
(LLC) cells to cisplatin. In contrast, the clinical drug andrographolide (Andro)
suppressed autophagy and enhanced cisplatin-mediated apoptosis in these cells.
Using two murine lung cancer models, including a subcutaneously inoculated LLC
model and an orthotopic LLC implantation model, we investigated the therapeutic
efficacy of the combined treatment of cisplatin and Andro. Compared with the sole
cisplatin treatment, combining cisplatin with Andro potentially inhibited tumor
growth, reduced the incidence of lung metastases, and relieved renal tubular
damage. Moreover, the combined treatment prolonged the life span of tumor-bearing
mice. TUNEL and immunohistochemistry assays showed the increase in apoptotic
cells and the decrease in both conversion of LC3B-I to LC3B-II and Atg5 protein
expression in the tumor tissues from mice with the combined treatment. These
results suggest that Andro offers an ideal candidate of autophagy inhibitors in
clinical application, and combination of cisplatin with Andro could be a
promising strategy for the treatment of lung cancer.
PMID- 28692437
TI - Codelivery of salinomycin and docetaxel using poly(D,L-lactic-co-glycolic acid)
poly(ethylene glycol) nanoparticles to target both gastric cancer cells and
cancer stem cells.
AB - Cancer stem cells (CSCs) in gastric cancer (GC) have been established recently as
key therapeutic targets for the successful treatment of GC. Emerging evidence
suggests that both CSCs and cancer cells should be eradicated to achieve optimal
therapeutic efficacy. In the present study, salinomycin, which has been reported
to kill CSCs, was used in combination with docetaxel, a chemotherapeutic drug
that is used as first-line therapy in GC, to eradicate both GC stem cells (SCs)
and cancer cells. Salinomycin and docetaxel were loaded separately into poly(D,L
lactic-co-glycolic acid)-poly(ethylene glycol) nanoparticles of ~140 nm with a
narrow size distribution, high drug loading, and sustained drug release. GC SCs
were isolated by magnetic-activated cell sorting on the basis of CD44 expression
as the CSC phenotype. CD44 GC SCs showed the characteristics of CSCs, including
increased SC gene expression, tumorsphere formation capacity, and tumorigenicity
in nude mice. We found that both salinomycin and salinomycin-loaded nanoparticles
(salinomycin-NPs) could selectively eradicate GC SCs, as reflected by reduced
tumorsphere formation capacity and the frequency of CD44 GC cells, whereas
docetaxel and docetaxel-loaded nanoparticles (docetaxel-NPs) could significantly
eradicate GC cells. In nude mice bearing GC xenografts, salinomycin-NPs and
salinomycin significantly decreased the intratumor population of GC SCs. Notably,
salinomycin-NPs combined with docetaxel-NPs suppressed tumor growth more
effectively than did salinomycin combined with docetaxel, single salinomycin-NPs,
or docetaxel-NPs. Therefore, salinomycin-NPs combined with docetaxel-NPs
represent a promising strategy for the treatment of GC by eradicating both GC SCs
and cancer cells.
PMID- 28692438
TI - Prophylaxis of postoperative complications after craniotomy.
AB - PURPOSE OF REVIEW: This review reports an update of the evidence on practices
applied for the prevention and management of the most common complications after
craniotomy surgery. RECENT FINDINGS: Latest guidelines support the combined
thromboprophylaxis with the use of both mechanical and chemical modalities,
preferably applied within 24 h after craniotomy. Nevertheless, a heightened risk
of minor hemorrhagic events remains an issue of concern. Postoperative nausea and
vomiting (PONV) and pain constitute the complications most commonly encountered
during the first 24 h postcraniotomy. Recently, neurokinin type-1 receptor
antagonists have been tested as adjuncts for PONV prophylaxis with encouraging
results, whereas dexmedetomidine and gabapentinoids emerge as promising
alternatives for postcraniotomy pain management. The available data for seizure
prophylaxis following craniotomy lacks scientific quality; thus, this remains
still a debatable issue. Significantly, a growing body of evidence supports the
superiority of levetiracetam over the older antiepileptic drugs (AEDs), in terms
of efficacy and safety. SUMMARY: Optimum management of postoperative
complications is incorporated as an integral part of the augmented quality of
care in patients undergoing craniotomy surgery, aiming to improve outcomes. This
review may serve as a benchmark for neuroanesthetists for heightened clinical
awareness and prompt institution of well-documented practices.
PMID- 28692439
TI - Lipid emulsion in local anesthetic toxicity.
AB - PURPOSE OF REVIEW: Enthusiasm for regional anesthesia has been driven by
multimodal benefits to patient outcomes. Despite widespread awareness and
improved techniques (including the increasing use of ultrasound guidance for
block placement), intravascular sequestration and the attendant risk of local
anesthetic systemic toxicity (LAST) remains. Intravenous lipid emulsion (ILE) for
the treatment of LAST has been endorsed by anesthetic regulatory societies on the
basis of animal study and human case report data. The accumulated mass of
reporting now permits objective interrogation of published literature. RECENT
FINDINGS: Although incompletely elucidated the mechanism of action for ILE in
LAST seemingly involves beneficial effects on initial drug distribution (i.e.,
pharmacokinetic effects) and positive cardiotonic and vasoactive effects (i.e.,
pharmacokinetic effects) acting in concert. Recent systematic review by
collaborating international toxicologic societies have provided reserved
endorsement for ILE in bupivacaine-induced toxicity, weak support for ILE use in
toxicity from other local anesthetics, and largely neutral recommendation for all
other drug poisonings. Work since publication of these recommendations has
concluded that there is a positive effect on survival for ILE when animal models
of LAST are meta-analyzed and evidence of a positive pharmacokinetic effect for
lipid in human models of LAST. SUMMARY: Lipid emulsion remains first-line therapy
(in conjunction with standard resuscitative measures) in LAST. Increasing
conjecture as to the clinical efficacy of ILE in LAST, however, calls for high
quality human data to refine clinical recommendations.
PMID- 28692440
TI - Cefepime Associated With Phenytoin Induced Stevens-Johnson Syndrome.
AB - We describe a recent case of Stevens-Johnson Syndrome. A 49-year-old man was
admitted to the Intensive Care Unit of an Anaesthesia and Resuscitation
Department because of a Fournier gangrene that derived in a sepsis, ventilator
associated pneumonia, and renal failure. He was under treatment with cefepime and
suffered a generalized status epilepticus, so started treatment with phenytoin.
The next day he developed a "maculous cutaneous eruption in trunk and lower
limbs" compatible with a Stevens-Johnson Syndrome. Stevens-Johnson Syndrome is a
very severe and potentially fatal multiorganic disease, especially when present
in critically ill patients, with a strong drug-related etiology, especially with
antiepileptic drugs.
PMID- 28692441
TI - Histocompatibility and management of the highly sensitized kidney transplant
candidate.
AB - PURPOSE OF REVIEW: Increasing national participation in kidney paired donation
and implementation of new sharing policies via the current kidney allocation
system have brought about greater opportunities for the most highly sensitized
patients awaiting a kidney transplant. The purpose of this review is to discuss
the application of histocompatibility data in the context of the clinical
practice of kidney transplantation as pertains to the sensitized candidate.
RECENT FINDINGS: With desensitization techniques, transplantation across
virtually any antibody barrier is technically feasible, but long-term outcomes
after transplantation are improved when the immunologic match between donor and
recipient is optimized. Solid-phase immunoassays have changed the landscape of
histocompatibility testing. These sensitive and specific assays for identifying
donor-specific antibody not only help determine feasibility of transplantation
but have enabled outcomes studies aimed at understanding the spectrum of risk
posed by different antibody profiles. This, in turn, has helped guide decision
making in donor selection, in particular for sensitized patients. SUMMARY:
Careful evaluation of donor-specific antibody profiles with individualized,
patient-specific determination of unacceptable antigens is necessary to ensure
that highly sensitized patients receive every opportunity for transplantation.
PMID- 28692442
TI - Current issues in allogeneic islet transplantation.
AB - PURPOSE OF REVIEW: Transplantation of allogenic pancreatic islets is a minimally
invasive treatment option to control severe hypoglycemia and dependence on
exogenous insulin among type 1 diabetes (T1D) patients. This overview summarizes
the current issues and progress in islet transplantation outcomes and research.
RECENT FINDINGS: Several clinical trials from North America and other countries
have documented the safety and efficacy of clinical islet transplantation for T1D
patients with impaired hypoglycemia awareness. A recently completed phase 3
clinical trial allows centres in the United States to apply for a Food and Drug
Administration Biologics License for the procedure. Introduction of anti
inflammatory drugs along with T-cell depleting induction therapy has
significantly improved long-term function of transplanted islets. Research into
islet biomarkers, immunosuppression, extrahepatic transplant sites and potential
alternative beta cell sources is driving further progress. SUMMARY: Allogeneic
islet transplantation has vastly improved over the past two decades. Success in
restoration of glycemic control and hypoglycemic awareness after islet
transplantation has been further highlighted by clinical trials. However, lack of
effective strategies to maintain long-term islet function and insufficient
sources of donor tissue still impose limitations to the widespread use of islet
transplantation. In the United States, wide adoption of this technology still
awaits regulatory approval and, importantly, a financial mechanism to support the
use of this technology.
PMID- 28692443
TI - A Single Test Combining Blood Markers and Elastography is More Accurate Than
Other Fibrosis Tests in the Main Causes of Chronic Liver Diseases.
AB - BACKGROUND AND GOAL: International guidelines suggest combining a blood test and
liver stiffness measurement (LSM) to stage liver fibrosis in chronic hepatitis C
(CHC) and non-alcoholic fatty liver disease (NAFLD). Therefore, we compared the
accuracies of these tests between the main etiologies of chronic liver diseases.
STUDY: Overall, 1968 patients were included in 5 etiologies: CHC: 698, chronic
hepatitis B: 152, human immunodeficiency virus/CHC: 628, NAFLD: 225, and
alcoholic liver disease (ALD): 265. Sixteen tests [13 blood tests, LSM
(Fibroscan), 2 combined: FibroMeters] were evaluated. References were Metavir
staging and CHC etiology. Accuracy was evaluated mainly with the Obuchowski index
(OI) and accessorily with area under the receiver operating characteristics
(F>=2, F>=3, cirrhosis). RESULTS: OIs in CHC were: FibroMeters: 0.812,
FibroMeters: 0.785 to 0.797, Fibrotest: 0.762, CirrhoMeters: 0.756 to 0.771, LSM:
0.754, Hepascore: 0.752, FibroMeter: 0.750, aspartate aminotransferase platelet
ratio index: 0.742, Fib-4: 0.741. In other etiologies, most tests had
nonsignificant changes in OIs. In NAFLD, CHC-specific tests were more accurate
than NAFLD-specific tests. The combined FibroMeters had significantly higher
accuracy than their 2 constitutive tests (FibroMeters and LSM) in at least 1
diagnostic target in all etiologies, except in ALD where LSM had the highest OI,
and in 3 diagnostic targets (OIs and 2 area under the receiver operating
characteristics) in CHC and NAFLD. CONCLUSIONS: Some tests developed in CHC
outperformed other tests in their specific etiologies. Tests combining blood
markers and LSM outperformed single tests, validating recent guidelines and
extending them to main etiologies. Noninvasive fibrosis evaluation can thus be
simplified in the main etiologies by using a unique test: either LSM alone,
especially in ALD, or preferably combined to blood markers.
PMID- 28692444
TI - Effect of Restorative Configurations and Occlusal Schemes on Strain Levels in
Bone Surrounding Implants.
AB - AIM: This study investigated strain levels during and after implant insertion,
and during and after simulated mastication, in splinted and nonsplinted
restorations with different occlusal schemes. MATERIALS AND METHODS: Fresh bovine
bone resembling type I jawbone was collected. Strain gauges were placed at each
implant's neck, one horizontally and one vertically. Strains at and after implant
insertion were recorded. The restoration was loaded with cyclic load simulating
mastication. Loading and residual strains were recorded for 6 experimental
loading types. RESULTS: At and after implant insertion, high horizontal strains
were measured. Full splint loading presented higher vertical compared with
horizontal strains (P < 0.05). Segmented cross-arch splint showed higher
horizontal strains (P < 0.05). Premolar loading guidance presented the most
favorable loading and residual strain results (P < 0.05). CONCLUSIONS: Splinting
implant restorations may reduce strain levels at implant neck area and provide
preferable strain distribution during cyclic loading.
PMID- 28692445
TI - Normal cerebral vascular pulsations in humans: changes with age and implications
for microvascular disease.
AB - BACKGROUND: Cerebral syndromes in older humans, secondary stroke in younger
persons following trauma, and sickle cell anaemia in children, are linked by
unexplained microvascular damage and high cerebral pressure or flow pulsations.
The aim of this study was to characterize age-related pressure and flow waveforms
patterns entering the brain, to explain these in terms of disturbed physiological
function, and to consider clinical implications. METHOD: Blood flow velocity
waves were measured in four cerebral vascular territories by transcranial Doppler
of 1020 apparently normal patients (497 men, 21-78 years). Central pressure
waveforms were generated from radial artery applanation tonometry with
SphygmoCor. Relationships were described in time and frequency domains. RESULTS
AND CONCLUSION: Flow waveforms entering the brain showed similar pattern to
central aortic pressure waveforms, and similar changes with age. Augmentation
index of flow and of pressure had high correlation at different ages, and in men
and women (r = 0.58, P < 0.01). Calculated cerebral vascular impedance was
similar in both sexes, and at different ages, with low modulus and phase,
indicating a dilated, passive cerebral vascular bed. This vascular bed is subject
to pressure and flow fluctuations generated directly by the heart and boosted by
strong wave reflections from the lower body. CONCLUSION: Cerebral microvascular
damage in older patients is attributable to high pulsatile pressure tearing the
delicate media, causing haemorrhage, and high pulsatile flow dislodging
endothelial cells, causing thrombosis and microinfarcts. High pulsations in older
patients are caused by early wave reflection from the lower body. Reduction of or
delay in wave reflection is a logical strategy for aortic stiffening in older
humans.
PMID- 28692446
TI - Ethnicity and arterial stiffness in children and adolescents from a Brazilian
population.
AB - BACKGROUND: Increased stiffness of large arteries is an important determinant of
cardiovascular disease risk. Higher values of arterial stiffness measured by
carotid-femoral pulse wave velocity (cf-PWV) have been measured in adult African
Americans compared with whites. Studies assessing ethnic differences in cf-PWV
among children and adolescents are scarce. This study sought to evaluate the
association between ethnicity and cf-PWV in Brazilian children and adolescents.
METHODS: Seven hundred and seventy-one children and adolescents (211 blacks and
560 nonblacks, 11.3 +/- 2.7 years) were included. Arterial stiffness was
evaluated by cf-PWV. The ethnic classification was obtained by a single
interviewer according to general phenotypes such as skin color, hair shape and
facial traces. RESULTS: Blood pressure was similar in blacks and nonblacks across
all pubertal stages. Differently, cf-PWV was higher in blacks than nonblacks
pubescent (5.9 +/- 0.7 vs. 5.6 +/- 0.8 m/s, P = 0.001) and postpubescent (6.1 +/-
0.7 vs. 5.7 +/- 0.7 m/s, P = 0.042), whereas no difference was detected between
blacks and nonblacks prepubescent. These analyses were adjusted for sex, age,
height, BMI, SBP and heart rate. CONCLUSION: Our study showed that higher cf-PWV
values in blacks appear in adolescence and are independent of blood pressure
values. Therefore, our data suggest adolescence as the key phase for the
appearance of the vascular profile found in adults black individuals.
PMID- 28692447
TI - Communicating the benefits and risks of inflammatory bowel disease therapy to
patients and families.
AB - PURPOSE OF REVIEW: Treatment options for inflammatory bowel disease (IBD) have
rapidly expanded as the treatment paradigm has shifted from controlling symptoms
to reducing lifetime inflammatory burden. Families are confronted with the actual
and perceived risks of this ever-expanding array of choices. We aim to review the
shared decision-making process in pediatric IBD to ensure an optimal therapeutic
plan for the child and their family. RECENT FINDINGS: Mucosal healing is a
critical treatment target in pediatric IBD but it may not coincide with clinical
symptoms. Evidence-based therapies carry important risks, some of which may be
less severe than previously suspected, and a family's understanding of these
risks plays a crucial role in how they make health decisions. To form an
effective shared therapeutic plan, the physician must incorporate an
understanding of the values of both the child and family along with their lived
experience of illness. SUMMARY: To limit harm and promote health in pediatric
IBD, the physician must communicate collaboratively with the child and their
family to form mutually understood goals of care - both subjective experiential
and objective biological - and appreciate actual and perceived risks of treatment
options to effectively educate families and navigate toward the best treatment
choices. VIDEO ABSTRACT.
PMID- 28692448
TI - The use of biosimilars in paediatric inflammatory bowel disease.
AB - PURPOSE OF REVIEW: After expiry of the patent of originator anti-tumor necrosis
factor drug infliximab (Remicade), CT-P13 was in 2013 the first infliximab
biosimilar to be approved by the European Medicine Agency (EMA) for the same
indications as the reference drug, including paediatric inflammatory bowel
disease (IBD). The approval was based on extrapolation, after extensive in-vitro
studies and clinical experience in patients with ankylosing spondylitis and
rheumatoid arthritis. The extrapolation of CT-P13 to IBD and to paediatric
patients raised concerns among paediatric IBD specialists. RECENT FINDINGS: Now,
almost 4 years later, we can conclude that those concerns have been resolved.
There are a growing number of postmarketing studies and real-life data, so far
mostly in adults and some in children with IBD. These studies show reassuring
comparable efficacy, safety and immunogenicity between CT-P13 and the reference
Infliximab. CONCLUSION: In Europe, biosimilars are increasingly regularly
prescribed drugs in paediatric IBD. Due to their lower cost, treatment expenses
have gone down considerably (up to 30% or more in some countries) and patient
access has improved. However, additional well designed studies to investigate
long term follow-up of biosimilars in children are still needed. In addition,
clinical studies addressing pharmacokinetics, pharmacodynamics and optimal use of
infliximab (originator as well as biosimilar) are still desirable.
PMID- 28692449
TI - Fidget spinners: Purported benefits, adverse effects and accepted alternatives.
AB - PURPOSE OF REVIEW: In the span of a few months, fidget spinners have caught the
eyes of millions of children, parents, educators and paediatricians. Fidget
spinners, hand-held toys designed to spin freely in your grasp, have become a
source of entertainment for consumers of all ages. Despite a lack of scientific
evidence, toy marketers have advertised the benefits of fidget spinners for
children with attention-deficit/hyperactivity disorder and other disorders (e.g.
autism, anxiety, sensory issues). Parents are incentivized by these purported
benefits to purchase fidget spinners to improve their child's concentration and
decrease stress. RECENT FINDINGS: While fidget spinners are a new phenomenon,
existing therapy toys (e.g. sensory putty) have been used by occupational
therapists for similar reasons, with comparably little research supporting these
claims. The purpose of this review is to explore literature regarding sensory
toys and examine educator/professional-reported concerns and medical adverse
effects of using fidget spinners. SUMMARY: Due to a recent surge in popularity,
fidget spinners and other self-regulatory occupational therapy toys have yet to
be subjected to rigorous scientific research. Thus, their alleged benefits remain
scientifically unfounded. Paediatricians should be aware of potential choking
hazards with this new fad, and inform parents that peer-reviewed studies do not
support the beneficial claims.
PMID- 28692450
TI - Advances in midface reconstruction: beyond the reconstructive ladder.
AB - PURPOSE OF REVIEW: This article reviews the anatomy and function of the midface,
defect classifications and the breadth of common and novel reconstructive
techniques including medical modeling, dental splints, and dental rehabilitation.
RECENT FINDINGS: Historically many classification systems for midface and
maxillary defects exist but most defects are unique and an individualized
approach is required. There has been an increased interest in using regional
pedicled flaps with bone for reconstruction. Free flap reconstruction with the
osteocutaneous radial forearm and fibula flap have been recently modified to
increase the success of osseointegrated implants. Scapular free flap
reconstruction has become increasingly popular because of the versatility, good
bony contour match, and long pedicle length with the scapular tip flap. Dental
splints are more cost effective than medical modeling and cutting guides but both
techniques are complimentary in complex reconstruction. SUMMARY: Midface
reconstruction is a unique and challenging surgery demonstrated by the numerous
classification systems and techniques available to reconstruct. Recent
developments have further augmented these challenging reconstructions.
PMID- 28692451
TI - The value of musculoskeletal ultrasound in geriatric care and rehabilitation.
AB - The WHO reports that one of the major chronic conditions affecting the elderly
worldwide is musculoskeletal disorders that are associated with long-term pain
and disability. Considering the healthcare needs of the elderly (i.e.
comprehensive, accessible, efficient) and the advantages of ultrasound (US) use
(patient-friendly, convenient, cost-effective, and does not require exposure to
radiation or magnetic fields), there seems to be a 'gap' in the actual clinical
practice. In this paper, we aimed to highlight the potential value of US imaging
in the management of the elderly with a wide spectrum of musculoskeletal
conditions (degenerative/rheumatic joint diseases, falls/trauma, nursing care,
peripheral nerve problems, sarcopenia, and interventions). In this respect,
electronic databases (ISI Web of Science, PubMed, Elsevier Science Direct) and
reference lists of relevant articles/reviews were screened by two blinded
investigators for each topic. The main medical subject heading terms selected to
capture the most relevant papers on the topics in accordance with the literature
were knee/hip/hand osteoarthritis, prevalence, rotator cuff injury, lateral
epicondylitis, tendinopathy, rheumatoid arthritis, Sjogren's syndrome,
polymyalgia rheumatica, crystal arthropathies, gout, pseudogout, carpal tunnel
syndrome, fall, fractures, hematoma, pressure ulcer, ultrasonography,
interventional, sarcopenia, body composition, rehabilitation, frail elderly, and
aged. The search was limited to peer-reviewed full-text English journals starting
from the earliest papers to May 2017. A study population (or part of the study
population) of adults older than 65 years (if possible) was included. We
especially underscore the use of US by clinicians as an extension of their
physical examination or as a practical guide for an immediate intervention.
PMID- 28692452
TI - Acetabular Protrusio in Patients With Osteogenesis Imperfecta: Risk Factors and
Progression.
AB - BACKGROUND: Osteogenesis imperfecta (OI) is a genetic disorder commonly
associated with osteopenia, osteoporosis, bone fractures, bone deformities, and
other clinical features. A frequent radiologic finding with OI is acetabular
protrusio (AP). We hypothesized that AP develops in patients with OI over time.
In addition, we hypothesized that AP also develops in patients with OI without
radiographic evidence of AP on initial examination. METHODS: Medical records and
radiographs of 55 patients (109 hips) diagnosed with OI evaluated at our
institution were retrospectively reviewed. Previously established radiographic
criteria using the center-edge (CE) angle of Wiberg, position of the acetabulum
relative to the iliopectineal line, crossing of the acetabulum across the
ilioischial (Kohler) line, and position of the teardrop figure relative to the
ilioischial (Kohler) line were utilized to assess AP severity. In addition,
pharmacological treatments and patient factors including body mass index (BMI)
were recorded. Radiographs of patients with OI that were taken >=2 years apart
were analyzed utilizing AP radiographic criteria to assess for changes. The
changes in AP-related measurements were standardized by distance or degree per
year. In addition, patient factors were evaluated for associations with AP
development. RESULTS: In this series of 109 hips (55 patients), incidence of AP
in earliest radiographs was 45% (49/109). Patients with OI type I and III
demonstrated the highest incidence of AP (65%). Among the hips that did not meet
the criteria for AP in their early radiographs, 24 (40%) were positive for AP by
their latest radiograph. In the hips that initially presented with AP, 42% showed
increased CE angles on later radiographs. Twenty-six hips (24%) showed either no
observable changes or reduced CE angles. Risk factors that were significantly
associated with greater odds of developing AP included (1) an age under 12; (2) a
BMI>25; (3) presence of AP of the contralateral hip; and (4) female sex.
Bisphosphonates, vitamin D, physical therapy, and other drugs related to
treatment of OI reduced the risk of developing AP but did not achieve statistical
significance. CONCLUSIONS: AP is a common finding in OI patients (54%). Among
hips of OI patients that met criteria for AP in early radiographs, 42% (20/48)
demonstrated greater CE angles in their latest radiographs. Similar changes were
observed in OI patients who did not initially meet criteria for diagnosis for AP.
However, CE angle measurements between the 2 groups did not significantly differ
(P=0.71). In terms of Kohler line crossing, patients that met criteria for AP in
early radiographs had significantly greater change per year than those that did
not have AP criteria (P<0.05). The findings suggest AP may develop over time in
patients with OI and may be influenced by patient factors such as age, sex, and
BMI. In addition, unilateral AP may have a significant impact on the development
of AP of the contralateral hip. LEVEL OF EVIDENCE: Level IV-retrospective case
series.
PMID- 28692453
TI - Neuromagnetic evaluation of a communication support system for hearing-impaired
patients.
AB - Hearing-impaired patients often encounter obstacles in communication. Not all of
them wear hearing aids, citing issues with usage difficulty and discomfort in
wearing. To overcome these difficulties, a new endeavor was started to improve
sound intelligibility from the speaker's side. The present study objectively
evaluated an intelligible-hearing (IH) loudspeaker by means of
magnetoencephalography. Magnetic counterparts of mismatch negativity (MMNm) to
pronunciation ('mi' and 'ni') were recorded and compared when they were
transmitted from the IH loudspeaker and from a normal-hearing loudspeaker. On
using the IH loudspeaker, the peak latency was found to be significantly
shortened. In the case of hearing-impaired participants, marked MMNm responses
were observed only when the IH loudspeaker was used. These findings suggest that
improving sound intelligibility may be a supportive and rehabilitative approach
for hearing-impaired patients.
PMID- 28692454
TI - Phosphorylation of CYFIP2, a component of the WAVE-regulatory complex, regulates
dendritic spine density and neurite outgrowth in cultured hippocampal neurons
potentially by affecting the complex assembly.
AB - Actin dynamics is a critical mechanism underlying many cellular processes in
neurons. The heteropentameric WAVE-regulatory complex (WRC), consisting of WAVE,
CYFIP1/2, Nap, Abi, and HSPC300, is a key regulator of actin dynamics that
activates the Arp2/3 complex to initiate actin polymerization and branching. The
WRC is basally inactive because of intermolecular interactions among the
components, which can be modulated by bindings of phospholipids and Rac1, and
phosphorylations of WAVE and Abi. However, the phosphorylation of other
components of WRC and their functional significance remain largely unknown. To
address this issue, we focused on CYFIP1/2, in which we found two brain-specific
phosphorylation sites (S582 of CYFIP2 and T1068/T1067 of CYFIP1/2) from a
publicly available phosphoproteome database. To understand their functional
effects, we overexpressed wild-type, phospho-blocking, or phospho-mimetic mutants
of CYFIP2 in cultured hippocampal neurons, and found that only T1067A CYFIP2
decreased the density of stubby spines. Moreover, overexpression of wild-type
CYFIP2 increased neurite length, but T1067A did not exert this effect. To
understand the mechanism, we modeled CYFIP2 phosphorylation in the crystal
structure of WRC and found that T1067 phosphorylation could weaken the
interaction between CYFIP2 and Nap1 by inducing conformational changes of CYFIP2
alpha-helical bundles. In the co-immunoprecipitation assay, however, wild-type,
T1067A, and T1067E CYFIP2 showed similar interaction levels to Nap1, suggesting
that T1067 phosphorylation alone is not sufficient to disrupt the interaction.
Considering that the activation of WRC requires disassembly of the complex, our
results suggest that T1067 phosphorylation, together with other factors, could
contribute toward the activation process.
PMID- 28692455
TI - Relationship between the use of intuition in clinical practice and the clinical
competence of critical care nurses.
AB - INTRODUCTION: Clinical competency has been the main focus of nurse educational
systems. To further it, the concept of intuition was introduced into nursing in
the 1970s. Benner's theory proposed that greater use of intuition was linked to
higher clinical competence; however, there is still a paucity of data to verify
this theory. Therefore, the current study was conducted to assess the
relationship between the use of intuition in clinical practice and the clinical
competence of critical care nurses. METHODS: In this correlational study, 88
critical care nurses were recruited as convenience. The tools included a 'use of
intuition in clinical practice' scale devised by the researcher, and a 'clinical
competence' instrument. The gathered data were analyzed by SPSS version 20.0
software, using descriptive and inferential statistics. RESULTS: Of the 88
participants, 73.9% were women and 93.2% were at undergraduate level. The mean
and standard deviation of participants' age and work experience was 32.29 +/-
6.75 and 7.40 +/- 5.68 years, respectively. The Pearson correlation test revealed
no significant connection between the use of intuition in clinical practice and
the clinical competence of critical care nurses (r = 0.091, P = 0.398), and
produced similar results from the various demographic groups (P > 0.05).
CONCLUSION: In this study, no significant correlation between the use of
intuition and clinical competence in critical care nurses was found. This could
be attributed to intuition as a nursing skill being almost excluded from the
educational curriculum of nursing schools, and some background factors.
PMID- 28692456
TI - Focal necrotizing myopathy with 'dropped-head syndrome' induced by cobimetinib in
metastatic melanoma.
AB - Therapeutic advances derived from targeted therapy and immune checkpoint
inhibitors can improve melanoma prognosis. Since 2015, cobimetinib has been
approved in combination with vemurafenib in the first-line treatment for BRAF
mutated melanoma. For NRAS-mutated melanomas, MEK inhibition seems to be a
therapeutic target, and association with checkpoint inhibitor provides a further
therapeutic perspective. Infraclinical creatine phosphokinase (CPK) elevation is
an MEK inhibitor side effect. We describe a case of focal necrotizing myopathy
with 'dropped-head syndrome' induced by cobimetinib, 1 month after its
introduction. The clinical presentation comprised interscapular pain, axial
fatigue with cervical hypotonia, CPK elevation, intense fluorine-18
fluorodeoxyglucose uptake in cervical muscles, and necrotizing myopathy was
confirmed by muscle biopsy. Cobimetinib was temporarily discontinued, resulting
in CPK normalization. Re-evaluation showed partial response, motivating
continuation of combination therapy with a reduced dose of cobimetinib (40
mg/day). Because prescription of targeted therapies is likely to increase, this
adverse event should be known.
PMID- 28692457
TI - The thyroid cancer epidemic, 2017 perspective.
AB - PURPOSE OF REVIEW: Thyroid cancer incidence and mortality trends have been
identified as being consistent with overdiagnosis, and several recent efforts
have been made to mitigate this problem. RECENT FINDINGS: Major guidelines for
thyroid nodule management recommend against general biopsy of nodules less than 1
cm in size. Data supporting the safety of active surveillance of low-risk thyroid
cancers is now recognized. Tumors previously labeled as encapsulated follicular
variant papillary thyroid cancers are now recommended to be called noninvasive
follicular thyroid neoplasm with papillary-like nuclear features. SUMMARY:
Workup, diagnostic, and management of papillary thyroid cancer are changing
rapidly to accommodate the recognition that many thyroid cancers are low risk and
do not require aggressive, immediate intervention.
PMID- 28692458
TI - Angiographic and clinical outcomes after recanalization of coronary chronic total
occlusions with the Orsiro sirolimus-eluting stent compared with the resolute
zotarolimus-eluting stent.
AB - OBJECTIVE: The third generation drug eluting Orsiro stent had shown already
promising results in non-complex lesions. BACKGROUND: We evaluated angiographic
and 24 month clinical results of the sirolimus eluting Orsiro stents (O-SES)
after recanalization of coronary chronic total occlusions (CTO). Results were
compared with the zotarolimus eluting Resolute Integrity (R-ZES). METHODS: In a
prospective series 57 patients were treated with a R-ZES followed by 74 patients
treated with a O-SES stent. Angiographic follow up after 9 months and clinical
follow-up after 12 and 24 months was performed. RESULTS: In-stent late lumen loss
was 0.24+/-0.53 mm for the O-SES compared with 0.59+/-0.72 (P=0.01) for R-ZES.
Rates for TLR were similar (O-SES 10.0% versus R-ZES 11.1%, P=0.84). There was no
definite stent thrombosis. CONCLUSION: The O-SES resulted in a significant lower
late lumen loss but with similar clinical results up to 24 month compared to the
R-ZES after treatment of CTO lesions.
PMID- 28692459
TI - Comparative determinants of 5-year cardiovascular event rates in patients with
unprotected left main coronary artery disease.
AB - BACKGROUND: Diabetes mellitus (DM), low ejection fraction (EF), and the extent of
coronary artery disease (CAD) have all been identified as predictors of
cardiovascular events in multivessel disease, but their comparative contributions
to future risk remain unclear in patients with unprotected left main coronary
artery (ULMCA) disease. Through this study we aimed to categorize the risk for
cardiovascular events in patients with ULMCA disease using simple clinical
descriptors. PATIENTS AND METHODS: Our study included a total of 5975 patients
with ULMCA disease from the Interventional Research Incorporation Society-Left
MAIN Revascularization registry who were treated with percutaneous coronary
intervention (n=2850), coronary artery bypass grafting (n=2337), or medical
therapy alone (n=608). We categorized the risk for cardiovascular events using
simple clinical descriptors (DM, low EF, and the extent of CAD). The primary
outcome was a major adverse cardiac or cerebrovascular event (MACCE) (i.e. death
from any cause, stroke, myocardial infarction, or repeat revascularization).
RESULTS: Overall, the 5-year rate of MACCE was highest in the medical group,
lower in the percutaneous coronary intervention group, and lowest in the coronary
artery bypass grafting group (42.5, 25.7, and 19.9%, respectively; P<0.001). In
multivariable modeling, the presence of DM [hazard ratio (HR): 1.25; 95%
confidence interval (CI): 1.12-1.40; P<0.001], low EF of 40% or less (HR: 1.83;
95% CI: 1.56-2.15; P<0.001), and the extent of CAD (HR: 1.14; 95% CI: 1.08-1.21;
P<0.001) were independent predictors of MACCE; in addition, these factors were
consistently associated with a significantly higher risk for MACCE, regardless of
index treatment strategies. CONCLUSION: Simple clinical descriptors can assist
clinicians in identifying high-risk patients and in predicting future
cardiovascular events within the broad range of risk factors for ULMCA disease.
PMID- 28692460
TI - Coronary intervention for chronic total occlusion: current indications and future
directions.
AB - Chronic total occlusions (CTOs) are routinely encountered during coronary
angiography, but subsequent revascularization rates are low. This has likely been
driven by a historical belief that there is minimal clinical benefit and poor
success rates with a percutaneous coronary intervention (PCI). However, in the
current era, with the development of new techniques and tools, experienced
operators can perform CTO-PCI successfully in the majority of patients. The
current indications and benefit of CTO-PCI remain a topic of controversy and
debate. There is a growing body of predominantly nonrandomized studies reporting
both short-term and long-term outcomes of CTO-PCI. Recent and upcoming randomized
controlled trials in this area will also potentially expand indications in both
stable and patients with acute coronary syndrome. In this review, we will discuss
the current evidence for CTO-PCI and also future directions in this field.
PMID- 28692461
TI - Reappraisal of the Confusing Concept "Trichogerminoma" and the Ill-Defined
Finding "Cell Balls": Clinicopathologic Analysis of 6 Cases of Trichogerminoma
and Comparison With 2 Cases of Basal Cell Carcinoma With Cell Ball-Like Features.
PMID- 28692462
TI - Utility of Skin Biopsy in a Case of Progressive Myoclonic Epilepsy: Challenge.
PMID- 28692463
TI - Syringotropic Mycosis Fungoides: A Rare Form of Cutaneous T-cell Lymphoma
Enabling a Histopathologic "Sigh of Relief".
AB - Syringotropic mycosis fungoides (STMF) is a very rare variant of cutaneous T-cell
lymphoma. It follows a much milder disease course than its clinically
indistinguishable adnexal counterpart, folliculotropic mycosis fungoides (FMF).
We report a case of a 36-year-old man who presented with erythematous, studded
papules and plaques on the left upper extremity and right anterior thigh
diagnosed as mycosis fungoides (MF) Stage 1A on initial superficial shave biopsy.
Lesions recurred after initial improvement with narrow-band ultraviolet light
therapy demonstrating a concentration of abnormal lymphocytes around eccrine
sweat glands on repeat biopsy consistent with STMF. Although the deeper,
periadnexal infiltrate found in both STMF and FMF confers increased resistance to
skin-directed therapies effective in classic MF, these entities diverge with
respect to their clinical behavior. Syringotropism is a marker for increased
disease-specific survival, whereas even FMF carries a prognosis worse than
conventional MF. Increased awareness among the dermatopathology community of the
histopathologic distinction between STMF and FMF is essential to guide treatment
type, duration, and intensity in adnexal disease.
PMID- 28692464
TI - Melanocytes Pattern in the Normal Nail, With Special Reference to Nail Bed
Melanocytes.
AB - Previous studies of the density of melanocytes in the normal nail bed have had
conflicting results. This is unfortunate because knowing the normal values might
help the difficult distinction between a benign subungual melanotic macule and an
early melanoma in situ. Five specimens of normal nail unit were analyzed. On
hematoxylin and eosin-stained sections the melanocytes were undetectable. We
defined the melanocyte count (MC) as the number of melanocytes per 1-mm stretch
of nail epithelium. The mean MC for nail matrix was 6.86 with a range of 4-14.
The melanocytes were irregularly scattered in the basal and suprabasilar layer of
the matrix epithelium. Abundant and uneven cytoplasmic dendrites were focally
observed in the matrix. The MC for the nail bed ranged from 0 to 5 with a mean of
0.43. The melanocytes were restricted to the basal layer with thin cytoplasmic
dendrites. Two cases showed a complete absence of melanocytes in the nail bed. In
the ventral portion of the proximal nail fold, called the eponychium, the MC
ranged between 0 and 5/mm with a mean of 2.27/mm. In conclusion, we discovered
foci in normal nail beds, in which the melanocytic density can be relatively high
and reach the level seen in the matrix. HMB45 is more sensitive than
Microphtalmia-associated transcription factor (MITF) for the evaluation of
intraepithelial melanocytic density of the nail unit. If MITF is used alone in
the nail bed, its weak sensitivity may result in a false-negative interpretation
and may be wrongly reassuring in the evaluation of early melanomas. On
hematoxylin and eosin sections, basal and suprabasal nail keratinocytes are
sometimes crowded, showing oval or elongated dark-staining nucleus and a clear
cytoplasm and mimics a melanocytic proliferation. On HMB45 or Melan A staining,
the morphology and the distribution of the dendrites of matrical melanocytes can
mimic the dendritic pattern usually described in acral melanoma. Therefore, the
interpretation of nail melanocytic atypia must be prudent.
PMID- 28692465
TI - Epidermotropic Bullous and Erosive Metastatic Melanoma.
PMID- 28692466
TI - Osteoclast-Like Giant Cells in Malignant Melanoma: Unintentional Accident or
Strategic Recruitment?
PMID- 28692467
TI - Intravenous Tranexamic Acid Bolus plus Infusion Is Not More Effective than a
Single Bolus in Primary Hip Arthroplasty: A Randomized Controlled Trial.
AB - BACKGROUND: Preoperative administration of the antifibrinolytic agent tranexamic
acid reduces bleeding in patients undergoing hip arthroplasty. Increased
fibrinolytic activity is maintained throughout the first day postoperation. The
objective of the study was to determine whether additional perioperative
administration of tranexamic acid would further reduce blood loss. METHODS: This
prospective, double-blind, parallel-arm, randomized, superiority study was
conducted in 168 patients undergoing unilateral primary hip arthroplasty.
Patients received a preoperative intravenous bolus of 1 g of tranexamic acid
followed by a continuous infusion of either tranexamic acid 1 g (bolus-plus
infusion group) or placebo (bolus group) for 8 h. The primary outcome was
calculated perioperative blood loss up to day 5. Erythrocyte transfusion was
implemented according to a restrictive transfusion trigger strategy. RESULTS: The
mean perioperative blood loss was 919 +/- 338 ml in the bolus-plus-infusion group
(84 patients analyzed) and 888 +/- 366 ml in the bolus group (83 patients
analyzed); mean difference, 30 ml (95% CI, -77 to 137; P = 0.58). Within 6 weeks
postsurgery, three patients in each group (3.6%) underwent erythrocyte
transfusion and two patients in the bolus group experienced distal deep-vein
thrombosis. A meta-analysis combining data from this study with those of five
other trials showed no incremental efficacy of additional perioperative
administration of tranexamic acid. CONCLUSIONS: A preoperative bolus of
tranexamic acid, associated with a restrictive transfusion trigger strategy,
resulted in low erythrocyte transfusion rates in patients undergoing hip
arthroplasty. Supplementary perioperative administration of tranexamic acid did
not achieve any further reduction in blood loss.
PMID- 28692468
TI - A Prospective Randomized Multicenter Trial of Distal Pancreatectomy With and
Without Routine Intraperitoneal Drainage.
AB - OBJECTIVE: The objective of this study was to test the hypothesis that distal
pancreatectomy (DP) without intraperitoneal drainage does not affect the
frequency of grade 2 or higher grade complications. BACKGROUND: The use of
routine intraperitoneal drains during DP is controversial. Prior to this study,
no prospective trial focusing on DP without intraperitoneal drainage has been
reported. METHODS: Patients undergoing DP for all causes at 14 high-volume
pancreas centers were preoperatively randomized to placement of a drain or no
drain. Complications and their severity were tracked for 60 days and mortality
for 90 days. The study was powered to detect a 15% positive or negative
difference in the rate of grade 2 or higher grade complications. All data were
collected prospectively and source documents were reviewed at the coordinating
center to confirm completeness and accuracy. RESULTS: A total of 344 patients
underwent DP with (N = 174) and without (N = 170) the use of intraperitoneal
drainage. There were no differences between cohorts in demographics,
comorbidities, pathology, pancreatic duct size, pancreas texture, or operative
technique. There was no difference in the rate of grade 2 or higher grade
complications (44% vs. 42%, P = 0.80). There was no difference in clinically
relevant postoperative pancreatic fistula (18% vs 12%, P = 0.11) or mortality (0%
vs 1%, P = 0.24). DP without routine intraperitoneal drainage was associated with
a higher incidence of intra-abdominal fluid collection (9% vs 22%, P = 0.0004).
There was no difference in the frequency of postoperative imaging, percutaneous
drain placement, reoperation, readmission, or quality of life scores.
CONCLUSIONS: This prospective randomized multicenter trial provides evidence that
clinical outcomes are comparable in DP with or without intraperitoneal drainage.
PMID- 28692469
TI - Surgical Management of Gallbladder Cancer: Simple Versus Extended Cholecystectomy
and the Role of Adjuvant Therapy.
AB - OBJECTIVE: To assess if simple cholecystectomy with adjuvant therapy could
provide outcomes comparable to extended cholecystectomy. BACKGROUND: Current
guidelines recommend extended/radical cholecystectomy for T2/T3 gallbladder
cancer; however, many tumors are discovered incidentally at laparoscopic
cholecystectomy. METHODS: The national Cancer Data Base 2004 to 2014 was queried
for patients with pT2/T3 gallbladder adenocarcinoma who underwent resection.
Adjuvant therapy was defined as chemotherapy, with or without radiotherapy,
within 90 days of surgery. Baseline characteristics and overall survival were
compared by chi and Kaplan-Meier method, respectively. One-to-one propensity
score matching for receipt of adjuvant therapy was used to account for potential
selection bias. RESULTS: A total of 6825 patients were identified. Diagnosis was
made predominantly (78.9%) at the time of surgery or on pathology; 31.8% (2168)
received adjuvant therapy. The majority, 88.8% (6060), had a simple
cholecystectomy. Patients who received adjuvant therapy versus surgery alone were
more likely to: be younger, privately insured, have no comorbidities, pT3
disease, positive lymph nodes, positive resection margins, and extended
cholecystectomy. After matching, median survival was significantly longer for
extended cholecystectomy with adjuvant therapy (23.3 months) than cholecystectomy
with adjuvant therapy (16.4 months), which was significantly longer than either
simple (12.4 months) or extended (10.7 months) cholecystectomy alone (all log
rank P<0.001). CONCLUSIONS: Adjuvant therapy prolongs survival after resection of
T2/T3 tumors. Simple cholecystectomy with adjuvant therapy appears to be superior
to extended resection alone in the short term and may serve as a potential
alternative to re-resection in select high-risk individuals.
PMID- 28692470
TI - Is Annual Volume Enough? The Role of Experience and Specialization on Inpatient
Mortality After Hepatectomy.
AB - OBJECTIVE: To investigate the effect of subspecialty practice and experience on
the relationship between annual volume and inpatient mortality after hepatic
resection. BACKGROUND: The impact of annual surgical volume on postoperative
outcomes has been extensively examined. However, the impact of cumulative surgeon
experience and specialty training on this relationship warrants investigation.
METHODS: The New York Statewide Planning and Research Cooperative System
inpatient database was queried for patients' >=18 years who underwent wedge
hepatectomy or lobectomy from 2000 to 2014. Primary exposures included annual
surgeon volume, surgeon experience (early vs late career), and surgical
specialization-categorized as general surgery (GS), surgical oncology (SO), and
transplant (TS). Primary endpoint was inpatient mortality. Hierarchical logistic
regression was performed accounting for correlation at the level of the surgeon
and the hospital, and adjusting for patient demographics, comorbidities, presence
of cirrhosis, and annual surgical hospital volume. RESULTS: A total of 13,467
cases were analyzed. Overall inpatient mortality was 2.35%. On unadjusted
analysis, late career surgeons had a mortality rate of 2.62% versus 1.97% for
early career surgeons. GS had a mortality rate of 2.98% compared with 1.68% for
SO and 2.67% for TS. Once risk-adjusted, annual volume was associated with
reduced mortality only among early-career surgeons (odds ratio 0.82, P = 0.001)
and general surgeons (odds ratio 0.65, P = 0.002). No volume effect was seen
among late-career or specialty-trained surgeons. CONCLUSIONS: Annual volume alone
likely contributes only a partial assessment of the volume-outcome relationship.
In patients undergoing hepatic resection, increased annual volume did not confer
a mortality benefit on subspecialty surgeons or late career surgeons.
PMID- 28692471
TI - Minimally Invasive Thoracic Surgery 3.0: Lessons Learned From the History of Lung
Cancer Surgery.
PMID- 28692472
TI - Quantification of Immune Dysregulation by Next-generation Polymerase Chain
Reaction to Improve Sepsis Diagnosis in Surgical Patients.
AB - OBJECTIVES: To quantify immunological dysfunction in surgical patients with
presence/absence of sepsis using a droplet digital polymerase chain reaction
(ddPCR) transcriptomic analysis. The study also aims to evaluate this approach
for improving identification of sepsis in these patients. BACKGROUND: Immune
dysregulation is a central event in sepsis. Quantification of the expression of
immunological genes participating in the pathogenesis of sepsis could represent a
new avenue to improve its diagnosis. METHODS: Expression of 6 neutrophil protease
genes (MMP8, OLFM4, LCN2/NGAL, LTF, PRTN3, MPO) and also of 5 genes involved in
the immunological synapse (HLA-DRA, CD40LG, CD3E, CD28, ICOS) was quantified in
blood from 101 surgical patients with sepsis, 53 uninfected surgical patients,
and 16 blood donors by using ddPCR. Areas under receiver operating characteristic
curves (AUROC) and multivariate regression analysis were employed to test
individual genes and gene ratios to identify sepsis, in comparison with
procalcitonin. RESULTS: Sepsis-induced overexpression of neutrophil protease
genes and depressed expression of immunological synapse genes. MMP8/HLA-DRA,
LCN2/HLA-DRA outperformed procalcitonin in differentiating between patients with
sepsis and surgical controls in the AUROC analysis: LCN2/HLA-DRA: 0.90 (0.85
0.96), MMP8/HLA-DRA: 0.89 (0.84-0.95), procalcitonin: 0.80 (0.73-0.88) (AUROC,
confidence interval 95%), and also in the multivariate analysis: LCN2/HLA-DRA:
8.57 (2.25-32.62); MMP8/HLA-DRA: 8.03 (2.10-30.76), procalcitonin: 4.20 (1.15
15.43) [odds ratio (confidence interval 95%)]. Gene expression levels of HLA-DRA
were an independent marker of hospital mortality. CONCLUSIONS: Quantifying the
transcriptomic ratios MMP8/HLA-DRA, LCN2/HLA-DRA by ddPCR is a promising approach
to improve sepsis diagnosis in surgical patients.
PMID- 28692473
TI - To Bleed or Not to Bleed: Is That the Question?
PMID- 28692474
TI - Molecular Adsorbent Recirculating System Effectively Replaces Hepatic Function in
Severe Acute Liver Failure.
AB - BACKGROUND DATA: Patients with severe acute liver failure (ALF) have extreme
physiologic dysfunction and often die if transplantation is not immediately
available. Patients may be supported with MARS (Baxter International Inc.,
Deerfield, IL) until transplantation or spontaneous recovery occurs. We present
the largest series in the United States of MARS therapy as temporary hepatic
replacement for ALF. METHODS: MARS was used to support patients with severe liver
trauma (SLT), in ALF patients as a bridge to transplantation (BTT), and as
definitive therapy for toxic ingestion or idiopathic liver failure (DT) in a
level 1 trauma center and large transplant center. Patient demographics, etiology
of ALF, and laboratory values were recorded. Endpoints were patient survival +/-
liver transplant and/or recovery of liver function. RESULTS: Twenty-seven
patients with severe ALF received MARS therapy. Five patients with SLT had a 60%
survival with recovery of liver and renal function. Thirteen patients received
MARS as a BTT, of which 9 were transplanted with a 1-year survival of 78%
(program overall survival 85% at 1 year). All 4 who were not transplanted
expired. Nine patients with ALF from toxic ingestion received MARS as DT with
liver recovery and survival in 67%. MARS therapy resulted in significant
improvement in liver function, coagulation, incidence of encephalopathy, and
creatinine. CONCLUSIONS: MARS therapy successfully replaced hepatic function in
ALF allowing time for spontaneous recovery or transplantation. Spontaneous
recovery was remarkably common if support can be sustained.
PMID- 28692475
TI - Prophylactic Negative Pressure Dressing Use in Closed Laparotomy Wounds After
Abdominal Operations: What We Really Know?
PMID- 28692476
TI - Ten-year Outcomes of a Prospective Randomized Trial of Laparoscopic Gastric
Bypass Versus Laparoscopic Gastric Banding.
AB - OBJECTIVE: The primary endpoints of this study were long-term weight loss,
morbidity, and changes in comorbidities and quality of life. BACKGROUND:
Bariatric surgery is an effective option for the treatment of severe obesity and
its related comorbidities. However, few studies have reported on the long-term
outcome (>5 yrs) of bariatric surgery. METHODS: Between 2002 and 2007, 250
patients with a body mass index (BMI) of 35 to 60 kg/m were randomly assigned to
undergo laparoscopic gastric bypass or laparoscopic gastric banding. After
exclusions, 111 patients underwent gastric bypass and 86 patients underwent
gastric banding. Factors predictive of improved weight loss were analyzed using
multiple logistic regressions. RESULTS: At baseline, the mean age was 43 +/- 10
years and the mean BMI was 46.5 +/- 5.6 kg/m. At 10-year follow-up, the mean
total body weight loss for the entire cohort was -37.5 +/- 19.4 kg, -42.4 +/-
19.6 kg for gastric bypass versus -27.4 +/- 14.5 kg for gastric banding. Late
reoperation was significantly higher after gastric banding compared with the
gastric bypass group (31.4% vs. 8.1%, respectively, P < 0.01). For the entire
cohort, improvement or remission of diabetes occurred in 68%; 61% for
hypertension; and 57% for dyslipidemia. The long-term mortality for the entire
cohort was 1.0% at a mean follow-up of 9.5 +/- 0.4 years. Factors predictive of
improved weight loss included the type of operation (ie, gastric bypass), female
sex, and the absence of diabetes at baseline. At long-term follow-up, quality of
life continues to be improved from baseline for both the groups. CONCLUSIONS:
Bariatric surgery is an effective treatment for severe obesity with durable 10
year weight loss and improvement in comorbidities and quality of life. Compared
with gastric banding, gastric bypass was associated with better long-term weight
loss, lower rate of late reoperation, and improved remission of comorbidities.
PMID- 28692477
TI - R0 Versus R1 Resection Matters after Pancreaticoduodenectomy, and Less after
Distal or Total Pancreatectomy for Pancreatic Cancer.
AB - OBJECTIVE: The aim of this study was to decipher the true importance of R0 versus
R1 resection for survival in pancreatic ductal adenocarcinoma (PDAC). SUMMARY OF
BACKGROUND DATA: PDAC is characterized by poor survival, even after curative
resection. In many studies, R0 versus R1 does not result in different prognosis
and does not affect the postoperative management. METHODS: Pubmed, Embase, and
Cochrane databases were screened for prognostic studies on the association
between resection status and survival. Hazard ratios (HRs) were pooled in a meta
analysis. Furthermore, our prospective database was retrospectively screened for
curative PDAC resections according to inclusion criteria (n = 254 patients)
between July 2007 and October 2014. RESULTS: In the meta-analysis, R1 was
associated with a decreased overall survival [HR 1.45 (95% confidence interval,
95% CI 1.37-1.52)] and disease-free survival [HR 1.44 (1.30-1.59)] in PDAC when
compared with R0. Importantly, this effect held true only for pancreatic head
resection both in the meta-analysis [R0 >=0 mm: HR 1.21 (1.05-1.39) vs R0 >=1 mm:
HR 1.66 (1.46-1.89)] and in our cohort (R0 >=0 mm: 31.8 vs 14.5 months, P <
0.001; R0 >=1 mm, 41.2 vs 16.8 months; P < 0.001). Moreover, R1 resections were
associated with advanced tumor disease, that is, larger tumor size, lymph node
metastases, and extended resections. Multivariable Cox proportional hazard model
suggested G3, pN1, tumor size, and R1 (0 mm/1 mm) as independent predictors of
overall survival. CONCLUSION: Resection margin is not a valid prognostic marker
in publications before 2010 due to heterogeneity of cohorts and lack of
standardized histopathological examination. Within standardized pathology
protocols, R-status' prognostic validity may be primarily confined to pancreatic
head cancers.
PMID- 28692478
TI - Diagnosis of Vitality in Skin Wounds in the Ligature Marks Resulting From Suicide
Hanging.
AB - Ascertaining the vital origin of skin wounds is one of the most challenging
problems in forensic pathology. The forensic literature describes biomarkers and
methods for differentiating vital and postmortem wounds, although no clear
conclusions have been reached. The aim of this study was to characterize human
vital wounds by analyzing the concentrations of metallic ions and the expression
of P-selectin and cathepsin D in skin wounds in the ligature marks in a cohort of
suicidal hangings for which vitality was previously demonstrated.A total of 71
skin wounds were analyzed within a postmortem interval of 19 to 36 hours. The
concentration of Fe, Zn, Mg, and Ca and the expression of P-selectin and
cathepsin D were analyzed together and separately. The majority of autopsied
suicidal hangings were men (86%) with complete hanging mode (60.7%) in which
there was a high frequency of subcutaneous injuries (78.3%). High concentrations
of Ca and Mg compared with Fe and Zn were found. Ca and Zn concentrations
decreased, and Fe concentration increased with the seriousness of the injury. A
high percentage of moderately negative expression of both proteins was correlated
with subcutaneous injury and low or medium concentrations of Fe.In conclusion,
the joint study of metallic ions and proteins allows to characterize and to
differentiate an injured vital wound of noninjured skin, especially when the
damage in the tissue affects to the majority of the structures of the skin, but
these results will need to be complemented with other biomarkers in time
controlled samples to further help in the differentiation of vital and postmortem
wounds.
PMID- 28692479
TI - Association of Waist-Hip Ratio to Sudden Cardiac Death and Severe Coronary
Atherosclerosis in Medicolegal Autopsies.
AB - Various modifiable and nonmodifiable risk factors, such as abdominal obesity, are
known to affect the development of atherosclerotic cardiovascular disease and
subsequent sudden cardiac death (SCD). The waist-hip ratio is a surrogate marker
of visceral obesity that has been shown in various studies to be a better
predictor of cardiovascular risk than the body mass index (BMI), a measurement of
generalized obesity. Waist-hip ratio was measured prospectively on medicolegal
autopsies performed for 1 year, in addition to standard measurements of BMI and
heart weight, and histologic determination of severe coronary atherosclerosis
(SCA, coronary artery diameter stenosis >75%). Logistic modeling was performed to
determine any association between WHR, BMI, cardiovascular disease risk factors,
heart weight, and SCD or SCA. Waist-hip ratio was not shown to be statistically
significantly associated with either SCD (P = 0.68) or SCA (P = 0.14). Body mass
index was shown to be significantly associated with SCA (P < 0.001), and heart
weight was shown to be significantly associated with both SCD and SCA (P < 0.001,
both). Waist-hip ratio, as a surrogate marker of central obesity and increased
risk of atherosclerotic cardiovascular disease, is shown not to be statistically
significantly associated with either SCD or SCA in postmortem cases.
PMID- 28692480
TI - Association of plasminogen activator inhibitor-1 and low-density lipoprotein
heterogeneity as a risk factor of atherosclerotic cardiovascular disease with
triglyceride metabolic disorder: a pilot cross-sectional study.
AB - BACKGROUND: We hypothesized that an increase in plasminogen activator inhibitor 1
(PAI-1) might reduce low-density lipoprotein (LDL) particle size in conjunction
with triglyceride (TG) metabolism disorder, resulting in an increased risk of
atherosclerotic cardiovascular disease (ASCVD). METHODS: This study was carried
out as a hospital-based cross-sectional study in 537 consecutive outpatients
(mean age: 64 years; men: 71%) with one or more risk factors for ASCVD from April
2014 to October 2014 at the Cardiovascular Center of Nihon University Surugadai
Hospital. The estimated LDL-particle size was measured as relative LDL migration
using polyacrylamide gel electrophoresis with the LipoPhor system.The plasma PAI
1 level, including the tissue PA/PAI-1 complex and the active and latent forms of
PAI-1, was determined using a latex photometric immunoassay method. RESULTS: A
multivariate regression analysis after adjustments for ASCVD risk factors showed
that an elevated PAI-1 level was an independent predictor of smaller-sized LDL
particle in both the overall patients population (beta=0.209, P<0.0001) and a
subset of patients with a serum low-density lipoprotein cholesterol (LDL-C) level
lower than 100 mg/dl (beta=0.276, P<0.0001). Furthermore, an increased BMI and TG
rich lipoprotein related markers [TG, remnant-like particle cholesterol,
apolipoprotein (apo) B, apo C-II, and apo C-III] were found to be independent
variables associated with an increased PAI-1 level in multivariate regression
models. A statistical analysis of data from nondiabetic patients with well
controlled serum LDL-C levels yielded similar findings. Furthermore, in the 310
patients followed up for at least 6 months, a multiple-logistic regression
analysis after adjustments for ASCVD risk factors identified the percent changes
of the plasma PAI-1 level in the third tertile compared with those in the first
tertile as being independently predictive of decreased LDL-particle size [odds
ratio (95% confidence interval): 2.11 (1.12/3.40), P=0.02]. CONCLUSION: The
plasma PAI-1 levels may be determined by the degree of obesity and TG metabolic
disorders. These factors were also shown to be correlated with a decreased LDL
particle size, increasing the risk of ASCVD, even in nondiabetic patients with
well-controlled serum LDL-C levels.
PMID- 28692481
TI - Differences in coronary plaque characteristics between patients with and those
without peripheral arterial disease.
AB - INTRODUCTION: Cardiovascular mortality of patients with combined peripheral
arterial disease (PAD) and coronary artery disease (CAD) is twice as high as that
in those with either disease alone. It is known that patients with PAD undergoing
percutaneous coronary intervention have a higher incidence of adverse cardiac
events such as myocardial infarction or target vessel revascularization.
OBJECTIVE: In this study, we compared the detailed characteristics of culprit and
nonculprit plaques between patients with and those without PAD using optical
coherence tomography. PATIENTS AND METHODS: We performed propensity score
matching using the following variables: (i) age; (ii) sex; (iii) clinical
presentation; (iv) diabetes mellitus; (v) hyperlipidemia; (vi) smoking; (vii)
hypertension; (viii) BMI; and (ix) coronary lesion location. Finally, we matched
34 culprit lesions and 30 nonculprit lesions in patients with PAD to 68 culprit
lesions and 60 nonculprit lesions in patients without PAD (1 : 2 ratio). RESULTS:
In culprit lesions, PAD patients when compared with those without PAD had a
higher prevalence of lipid-rich plaque (73.5 vs. 51.5%; P=0.033), higher lipid
index (1744+/-1110 vs. 1246+/-656; P=0.043), calcification (79.4 vs. 58.8%;
P=0.039), macrophage accumulation (70.6 vs. 48.5%; P=0.034), and cholesterol
crystals (32.4 vs. 10.3%; P=0.006). In nonculprit lesions, PAD patients had a
higher prevalence of calcification (76.7 vs. 55.0%; P=0.046), macrophage
accumulation (63.3 vs. 38.3%; P=0.025), and cholesterol crystals (36.7 vs. 16.7%;
P=0.034). CONCLUSION: Our study suggests greater coronary plaque vulnerability in
both culprit and nonculprit lesions in patients with PAD. This observation
underscores the need for more aggressive risk management in patients with
combined PAD and coronary artery disease.
PMID- 28692482
TI - Prognostic value of brachial-ankle pulse wave velocity in patients with non-ST
elevation myocardial infarction.
AB - OBJECTIVE: Brachial-ankle pulse wave velocity (baPWV) measurement is a well
established modality for assessing arterial stiffness and predicting
cardiovascular events. However, to our knowledge, its usefulness has not been
clarified among patients with non-ST-elevation myocardial infarction (NSTEMI).
This study assessed the prognostic value of baPWV in patients with NSTEMI.
PATIENTS AND METHODS: Patients (n=411, mean age, 63.8+/-13.5 years, 75.2% men)
with NSTEMI who underwent a percutaneous coronary intervention and baPWV
measurement were recruited between January 2013 and December 2015. Cardiac
mortality and major adverse cardiovascular events (MACE) including cardiac death,
re-acute myocardial infarction, revascularization, heart failure, and stroke
after discharge were analyzed. The mean follow-up duration was 350 days. RESULTS:
MACE and cardiac mortality occurred in 26 (6.3%) patients and 13 (3.1%) patients.
Kaplan-Meier survival curves showed that MACE and cardiac mortality were
significantly higher in patients with high baPWV (1708.0 cm/s). In multivariable
Cox regression analysis, high baPWV (hazard ratio: 2.55; 95% confidence interval:
1.03-6.30, P=0.043) was an independent predictor of MACE even after adjusting for
possible confounders. CONCLUSION: Our findings indicate that baPWV was a strong
independent prognostic factor of MACE in patients with NSTEMI. This suggests that
baPWV can be a useful prognostic factor in the clinical setting for easier and
less invasive prediction of MACE in patients with NSTEMI.
PMID- 28692483
TI - Bioresorbable vascular scaffolds: implication of very late scaffold thrombosis.
PMID- 28692484
TI - Meta-analysis of prophylactic hydration versus no hydration on contrast-induced
acute kidney injury.
AB - BACKGROUND: Guidelines recommend prophylactic hydration for all patients with
compromised renal function undergoing contrast exposure. However, the AMACING
study published recently showed a noninferior result of hydration compared with
no prophylaxis in high-risk patients and led to a heat discussion. This study
aimed to validate the effectiveness of prophylactic hydration in different
subsets of patients undergoing a contrast procedure. METHODS: We carried out a
meta-analysis of randomized-controlled trials to assess pooled estimates of
relative risk (RR) and 95% confidence intervals (CIs) for incidences of contrast
induced acute kidney injury (CI-AKI), in-hospital all-cause mortality, and need
for dialysis. RESULTS: Compared with no prophylaxis, patients receiving
prophylactic hydration had a lower risk of CI-AKI [RR: 0.66 (95% CI: 0.55-0.79);
P<=0.001; Pheterogeneity=0.42] and a lower risk of deaths of all-cause [RR: 0.57
(95% CI: 0.33-0.98); P=0.04; Pheterogeneity=0.47], but did not have a decreased
risk of need for dialysis [RR: 0.39 (95% CI: 0.12-1.23); P=0.11;
Pheterogeneity=0.31]. In subgroup analyses on the incidence of CI-AKI by baseline
estimated glomerular filtration rate (eGFR), no benefit from prophylactic
hydration was indicated in patients with a baseline eGFR ranging from 30 to 60
ml/min/1.73 m [RR: 1.02 (95% CI: 0.66-1.60); Pheterogeneity=0.66;
Pinteraction=0.03]. CONCLUSION: Our analysis indicated that prophylactic
hydration was associated with a lower risk of CI-AKI and all-cause deaths, but
not with the need for dialysis in the overall population. However, no
prophylactic hydration is noninferior to intravenous hydration on the incidence
of CI-AKI in patients with a baseline eGFR ranging from 30 to 60 ml/min/1.73 m.
PMID- 28692485
TI - Safety and tolerability of cariprazine in patients with acute exacerbation of
schizophrenia: a pooled analysis of four phase II/III randomized, double-blind,
placebo-controlled studies.
AB - Cariprazine, a potent dopamine D3 and D2 receptor partial agonist antipsychotic
with preferential binding to D3 receptors, is Food and Drug Administration
approved for treating schizophrenia and manic or mixed episodes of bipolar I
disorder. A post-hoc safety/tolerability analysis of data from the four acute
trials in the cariprazine schizophrenia clinical development program
(NCT00404573; NCT00694707; NCT01104766; NCT01104779) was carried out using the
overall safety population (all patients who received >=1 dose of study drug) and
modal daily dose subgroups (1.5-3, 4.5-6, and 9-12 mg/day). These exploratory
findings were summarized using descriptive statistics. Cariprazine was generally
well tolerated. The incidence of treatment-emergent adverse events versus placebo
was similar for cariprazine 1.5-3 mg/day and higher for cariprazine 4.5-6 and 9
12 mg/day; a dose-response relationship was observed for akathisia,
extrapyramidal symptoms, and diastolic blood pressure. The mean changes in
metabolic parameters were generally similar in cariprazine-treated and placebo
treated patients. There was no prolactin level increase or QTc value greater than
500 ms; small increases in mean body weight (~1to2 kg) versus placebo were
observed. Within the Food and Drug Administration-approved dose range (1.5-6
mg/day), cariprazine was generally safe and well tolerated in patients with
schizophrenia.
PMID- 28692486
TI - Standard and Amputation-Adjusted Body Mass Index Measures: Comparison and
Relevance to Functional Measures, Weight-Related Comorbidities, and Dieting.
AB - People with limb loss may misjudge weight-related health when not adjusting body
mass index (BMI) for amputation level. This cross-sectional, community-based
study compared BMI and amputation-adjusted BMI (A-BMI) and evaluated
relationships among BMI categories, function, and dieting. Subjects provided self
reported demographic, functional, and medical/prosthetic data including height
and weight and completed performance-based balance and gait measures. A Web-based
A-BMI calculator adjusted for amputation levels. Results for 294 subjects from 11
states (68.4% men; 76.5% white; average age, 55.6 [15.1] y) were reported, with
vascular (49.7%) and unilateral transtibial (40.8%) amputations as the most
common. Body mass index and A-BMI were closely correlated (Pearson r = 0.99), but
a BMI of 28.6 (6.7) was less than an A-BMI of 30.3 (6.2) (t test, P < 0.001).
Agreement among Centers for Disease Control BMI categories was moderate (kappa =
0.48); 39.7% of BMI categories were underestimated without adjusting for
amputations. Functional measures did not differ among BMI/A-BMI categories (P >
0.05). A larger than random proportion categorized as overweight by BMI dieted
(chi, P < 0.05), and people categorized as overweight by A-BMI did not (38.3%
classified as normal BMI). Functional abilities did not differ among BMI
categories (Kruskal-Wallis and analysis of variance, P > 0.05). People with limb
loss using BMI may underestimate weight-related health; a Web-based A-BMI
calculator may help monitor weight to make dieting decisions.
PMID- 28692487
TI - The Authors Respond.
PMID- 28692488
TI - Re: Dogmatists Cannot Learn.
PMID- 28692489
TI - The Estimation of Gestational Age at Birth in Database Studies.
AB - BACKGROUND: Studies on the safety of prenatal medication use require valid
estimation of the pregnancy duration. However, gestational age is often
incompletely recorded in administrative and clinical databases. Our objective was
to compare different approaches to estimating the pregnancy duration. METHODS:
Using data from the Clinical Practice Research Datalink and Hospital Episode
Statistics, we examined the following four approaches to estimating missing
gestational age: (1) generalized estimating equations for longitudinal data; (2)
multiple imputation; (3) estimation based on fetal birth weight and sex; and (4)
conventional approaches that assigned a fixed value (39 weeks for all or 39 weeks
for full term and 35 weeks for preterm). The gestational age recorded in Hospital
Episode Statistics was considered the gold standard. We conducted a simulation
study comparing the described approaches in terms of estimated bias and mean
square error. RESULTS: A total of 25,929 infants from 22,774 mothers were
included in our "gold standard" cohort. The smallest average absolute bias was
observed for the generalized estimating equation that included birth weight,
while the largest absolute bias occurred when assigning 39-week gestation to all
those with missing values. The smallest mean square errors were detected with
generalized estimating equations while multiple imputation had the highest mean
square errors. CONCLUSIONS: The use of generalized estimating equations resulted
in the most accurate estimation of missing gestational age when birth weight
information was available. In the absence of birth weight, assignment of fixed
gestational age based on term/preterm status may be the optimal approach.
PMID- 28692491
TI - A growing epidemic: cancer treatment consequences.
PMID- 28692490
TI - The future of digital games for HIV prevention and care.
AB - PURPOSE OF REVIEW: Although there has been a significant increase in mHealth
interventions addressing the HIV prevention and care continuum, interventions
using game mechanics have been less explored. Digital games are rapidly becoming
an important tool for improving health behaviors and supporting the delivery of
care and education. The purpose of this review is to provide a historical context
for the use of gamification and videogames (including those using virtual
reality) used in technology-based HIV interventions and to review new research in
the field. RECENT FINDINGS: A review of recently published (1 January 2016-31
March 2017) or presented abstracts (2016) identified a paucity of technology
based interventions that included gamification elements or any terms associated
with videogames or gameplay. A larger portfolio of digital gaming interventions
is in the pipeline. SUMMARY: Use of digital games that include elements of
gamification or consist of standalone videogames or virtual-reality-based games,
represent a promising intervention strategy to address the HIV prevention and
care continuum, especially among youth. Our review demonstrates that there is
significant room for growth in this area in designing, developing, testing and
most importantly, implementation and dissemination these novel interventions.
PMID- 28692492
TI - Criteria for the addition of prone imaging to myocardial perfusion single-photon
emission computed tomography for inferior wall.
AB - OBJECTIVE: Myocardial perfusion single-photon emission computed tomography
(SPECT) is occasionally suspected to generate images that represent either
ischemia or infarction for the inferior wall [right coronary artery (RCA)
disease] or attenuation artifacts because of the diaphragm. We often encounter
this. The application of prone imaging is advantageous in the differentiation of
RCA disease because of attenuation artifacts. If decreased accumulation of
radioisotopes is observed at the site with either RCA disease or attenuation
artifacts, then a criterion that enables the addition of prone imaging should be
implemented. Then, we evaluated sites where RCA disease and attenuation artifacts
would likely appear and investigated the threshold of decreased accumulation that
enables utilization of prone imaging. PATIENTS AND METHODS: The patients in this
study were divided into two groups: group A (20 patients) suspected to have
attenuation artifacts because of the diaphragm and group B (14 patients) with RCA
disease. Additional evaluation by prone imaging was performed in all patients. We
utilized a 20-segment quantitative perfusion SPECT polar map in the supine and
prone positions to compare the percentage increase in Thallium chloride (Tl) in
both groups. We then investigated the percent uptake (%uptake) value of decreased
accumulation in the inferior wall for the addition of prone imaging. RESULTS: The
highest %uptake was present in segments 3, 4, 5, and 10 in group A after the
prone imaging. Detection of attenuation artifacts from the diaphragm was easy in
segments 3, 4, 5, and 10, and we set the %uptake threshold at 62, 61, 71, and
76%, respectively, in the supine position for the addition of prone imaging.
CONCLUSION: A decrease of the %uptake in segments 3, 4, 5, and 10 after supine
imaging is presumed to result from attenuation artifact or RCA disease. We
established evaluation criteria for the addition of prone imaging in patients
with decreased accumulation in the inferior wall during supine imaging.
PMID- 28692493
TI - The application of technetium-99m-red blood cell scintigraphy in the diagnosis of
orbital cavernous hemangioma.
AB - OBJECTIVE: The purpose of this study was to evaluate the clinical value of
technetium-99m-red blood cell (Tc-RBC) scintigraphy in the diagnosis of orbital
cavernous hemangioma (OCH). PATIENTS AND METHODS: Forty-one patients with
pathologically confirmed orbital mass, of which 10 were OCH, underwent Tc-RBC
scintigraphy in this study. The scanning procedure included an initial perfusion
phase, followed by an early and a delayed blood pool phase. All patients
underwent ultrasonography and computed tomography (CT), and 15 patients also
underwent MRI. RESULTS: All 10 OCH patients had no abnormal findings on
radionuclide angiographic images and early blood pool phase, but increased
activity was found during delayed blood pool phase. All other non-OCH orbital
tumours did not have this tracer pattern. The radioactivity ratios of tumour to
nontumour were 2.96+/-0.05 and 1.14+/-0.25, respectively, which had a
statistically significant difference (t=15.18, P<0.001). Although nine of 10 OCH
patients were diagnosed correctly with one false-positive case using ultrasound,
both CT and MRI could not provide a definitive diagnosis. CONCLUSION: Tc-RBC
scintigraphy is a reliable and useful procedure for the diagnosis of OCH. It may
be considered as one of the routine clinical screening tools for the diagnosis of
OCH and as a complement investigation to ultrasonography and CT.
PMID- 28692494
TI - Diagnostic importance of 18F-FDG PET/CT parameters and total lesion glycolysis in
differentiating between benign and malignant adrenal lesions.
AB - PURPOSE: Benign adrenal lesions are prevalent in oncologic imaging and make
metastatic disease diagnoses difficult. This study evaluates the diagnostic
importance of metabolic, volumetric, and metabolovolumetric parameters measured
by fluorine-18-fluorodeoxyglucose (F-FDG) PET/CT in differentiating between
benign and malignant adrenal lesions in cancer patients. PATIENTS AND METHODS: In
this retrospective study, we evaluated F-FDG PET/CT parameters of adrenal lesions
of follow-up cancer patients referred to our clinic between January 2012 and
November 2016. The diagnosis of adrenal malignant lesions was made on the basis
of interval growth or reduction after chemotherapy. Patient demographics,
analysis of metabolic parameters such as maximum standard uptake value (SUVmax),
tumor SUVmax/liver SUVmean ratio (T/LR), morphologic parameters such as size,
Hounsfield Units, and computed tomography (CT) volume, and metabolovolumetric
parameters such as metabolic tumor volume and total lesion glycolysis (TLG) of
adrenal lesions were calculated. PET/CT parameters were assessed using the Mann
Whitney U-test and receiving operating characteristic analysis. RESULTS: In
total, 186 adrenal lesions in 163 cancer patients (108 men/54 women; mean+/-SD
age: 64+/-10.9 years) were subjected to F-FDG PET/CT for tumor evaluation. SUVmax
values (mean+/-SD) were 2.8+/-0.8 and 10.6+/-6; TLG were 10.8+/-9.2 and 124.4+/
347.9; and T/LR were 1+/-0.3 and 4.1+/-2.6 in benign and malignant adrenal
lesions, respectively. On the basis of the area under the curve, adrenal lesion
SUVmax and T/LR had similar highest diagnostic performance for predicting
malignant lesions (area under the curve: 0.993 and 0.991, respectively, P<0.001).
Multivariate logistic regression analysis showed that T/LR, adrenal lesion
SUVmax, and Hounsfield Units were independent predictive factors for malignancy
rather than TLG. CONCLUSION: Irrespective of whether TLG was statistically highly
significant for differentiating benign from malignant adrenal lesions, it did not
reach the expected performance with a low negative predictive value. This may be
because of the malignant but small and benign but large lesions on
metabolovolumetric calculation.
PMID- 28692495
TI - The clinical significance of technetium-99m methylene diphosphonate bone
scintigraphy findings in patients with rhabdomyolysis.
AB - OBJECTIVE: This study evaluated the relationship between bone scintigraphy
finding and clinical factors and assessed the prognostic value of bone
scintigraphy finding in patients with rhabdomyolysis. PATIENTS AND METHODS: We
retrospectively enrolled 143 patients with rhabdomyolysis who had undergone bone
scintigraphy. Bone scintigraphy was classified into three groups: no or equivocal
soft tissue uptake, a localized uptake, and a diffuse uptake. The relationship of
bone scintigraphy findings with clinical factors was evaluated. Multiple logistic
regression analysis was performed to identify the risk factors for acute renal
failure (ARF) and renal replacement therapy (RRT). RESULTS: Of 143 patients, 52
(36.4%) experienced ARF and 12 (8.4%) required RRT. Among cases caused by
exercise, 83.7% showed localized soft tissue uptake. Diffuse soft tissue uptake
was only shown among the patients with rhabdomyolysis caused by drug and toxin.
Patients with localized or diffuse soft tissue uptake had higher levels of serum
creatine kinase, myoglobin, aspartate aminotransferase, alanine aminotransferase,
and lactate dehydrogenase compared with patients with no or equivocal uptake
(P<0.05). Multiple logistic regression analysis showed that age, female sex, and
serum phosphate level were associated with a risk for ARF and only serum
creatinine level was associated with a risk for RRT (P<0.05). Bone scintigraphy
findings failed to show significance for predicting ARF and RRT (P>0.05).
CONCLUSION: Soft tissue uptake on bone scintigraphy in patients with
rhabdomyolysis was related to etiologies and showed limited value for predicting
ARF and RRT.
PMID- 28692496
TI - "Brighter Hours Will Come: " The Signet Ring of Florence Nightingale.
PMID- 28692497
TI - The Safety and Accuracy of Surgical Navigation Technology in the Treatment of
Lesions Involving the Skull Base.
AB - OBJECTIVE: As compared with the normal anatomy, structures of the skull base and
its surroundings have been dramatically altered of the lesion near the skull
base. How to remove the lesion at the skull base was mainly depending on
surgeon's personal experience during past years. In this study, the authors
explored the safety and accuracy of the surgical navigation system in resecting
lesions near the skull base. METHODS: The surgical cases consisted of 15 patients
who underwent surgery involving the skull base with the using of surgical
navigation technology. Five patients had adenoid cystic carcinoma at minor
salivary glands of the palate extending to the skull base and 10 patients were
suffered from bony ankylosis of temporomandibular joint. After the system
converted patient's computed tomography scans into three-dimensional
reconstructive images, preoperative planning and simulation of the operation
process could be made by surgeons. During the operation, the virtual images were
matched with the patient through individual registration. The system provided
surgeon with feedback about the operation on the screen instantly with moving the
navigated pointer. RESULTS: The application of surgical navigation system was
safe and reliable for resecting the ankylotic bone and identifying the extent of
tumors resection near the skull base. No complications including cerebrospinal
fluid leak, cranial nerve injuries, severe bleeding happened to those patients.
CONCLUSIONS: Given the safety and accuracy of the surgical navigation system,
surgery near the skull base appeared to be an ideal field for using with its
complex anatomy.
PMID- 28692498
TI - Distraction of Fronto-Orbital Segment as a Nonvascularized Bone Graft in
Craniosynostotic Patients.
AB - Fronto-orbital advancement using distraction techniques involves the dura left
attached to the osteotomized bone segment to avoid dead space formation and dural
injury, whereas it is impossible to reshape the supraorbital bar and the frontal
bone complex, when necessary. Our approach combines advantageous parts of
conventional and distraction osteogenesis techniques as remodel and distract the
supraorbital bar and frontal bone complex as a free bone graft. Twenty-seven
patients either being syndromic and nonsyndromic craniosynostosis, with at least
3 years of follow-up were reviewed in this study. Mean age of the patients at the
time of the operation was 23.44 +/- 18.42 months and mean operative time was 4.96
+/- 0.97 hours. Blood transfusion was required in all patients, with an average
of 112.04 +/- 44.60 mL. Amount of the distraction ranged 10 to 30 mm, a mean of
17.26 +/- 4.71 mm for the right side and 18.15 +/- 4.69 mm for the left side.
Mean duration of consolidation was 98.26 +/- 12.98 days and mean follow-up was
41.33 +/- 22.92 months. In this study, result of internal distraction of fronto
orbital segment as a nonvascularized bone graft in craniosynostotic patients is
reviewed to emphasize the efficacy of the nonvascularized bone graft distraction
in management of craniosynostosis. Graft distraction after fronto-orbital and
cranial vault remodeling appears to be safe and effective approach in correcting
severe craniosynostosis deformities especially necessitating asymmetrical
advancement.
PMID- 28692499
TI - Would Be Prophylactic Administrations of Low Concentration of Alendronate an
Alternative for Improving the Craniofacial Bone Repair? A Preliminary Study
Focused in the Period of Cellular Differentiation and Tissue Organization.
AB - BACKGROUND: Alendronate (ALN) is a nitrogen-bisphosphonate that may induce an
anabolic effect on craniofacial bone repair when administrated in low doses.
Based on this premise, this study analyzed the influence of prophylactic low
doses of ALN on bone healing in defects created in rabbit mandible. METHODS: A 5
* 2-mm diameter deep defect was created in the calvaria of 28 rabbits. Fourteen
of these rabbits received previously 50 MUg/kg of 1% sodium ALN for 4 weeks,
while the other rabbits received only 0.9% physiological saline solution
(control). Animals were euthanized at 15 and 60 days postsurgery (n = 7), and the
data were analyzed using histomorphometry and immunohistochemistry using the anti
CD34, bone morphogenetic protein -2 (BMP-2), and transforming growth factor (TGF)
beta1 antibodies. RESULTS: On the 15th day postsurgery, the specimens that
received previous treatment with ALN demonstrated large vascular lumen and
intense positivity to CD34 either concentrated in endothelium or cells spread
among the reparative tissue. These results coincided with intense positivity for
BMP-2+ cells and TGF-beta1 that was concentrated in both cells and perivascular
area. In contrast, the control group revealed scarce cells that exhibited CD34,
BMP-2+, and the TGF-beta1 was restricted for perivascular area on well-formed
granulation tissue. These patterns of immunohistochemical result, especially
found on the 15th day of analysis, seem to be responsible for the development of
larger quantities of bone matrix in the specimens that receive ALN on the 60th
day postsurgery. CONCLUSION: These preliminary results showed that the
prophylactic administration of low doses of ALN might be an alternative to
craniofacial bone craniofacial bone repair because it increases the
immunopositivity for TGF-beta1 and consequently improves the CD34+ and BMP-2+
cells on reparative sites.
PMID- 28692500
TI - Effect of Spreader Graft on Nasal Functions in Septorhinoplasty Surgery.
AB - OBJECTIVE: The authors aimed to investigate the effect of spreader grafts on
nasal function in septorhinoplasty (SRP). METHODS: A prospective randomized
double-blind study was conducted. Thirty patients who underwent SRP operation
between October 2011 and January 2013 were divided into 2 equal groups randomly.
Fifteen patients underwent SRP surgery without spreader graft technique (Group I)
and 15 patients underwent SRP surgery with spreader grafts (Group II).
Preoperative and postoperative evaluation included visual analog score (VAS) and
acoustic rhinometry test. RESULTS: Visual analog scores and acoustic rhinometry
measurements of Group I and Group II patients were compared. Statistically
significant difference was found for VAS scores of both the sides of the nasal
cavity (both before and after topical decongestion) (P < 0.05), except for the
VAS on the right side of the nasal cavity before decongestion (P > 0.05). On
acoustic rhinometry test the difference was statistically significant for minimal
cross-sectional area (MCA) and volumetric values (VOL)-MCA1, MCA2, VOL1, VOL2
values on the left side of the nasal cavity (both before and after topical
decongestion) (P < 0.05) but not on the right side of the nasal cavity (P >
0.05). CONCLUSIONS: Performing spreader graft technique in SRP surgery can
prevent the narrowing of the internal nasal valve area after surgery and maintain
adequate airway for respiration.
PMID- 28692501
TI - Modified Medial Ramus Retractor to Facilitate Horizontal Osteotomy During
Sagittal Split Ramus Osteotomy Procedure.
AB - Introducing a horizontal osteotomy is the first and a critical step in sagittal
split ramus osteotomy procedure. Identification of the lingula and medial
displacement of the vital structures entering the inferior alveolar foramen are
of paramount importance in ensuring a risk-free placement of the medial cut with
bur or a saw. Quite often, identification of lingula and retrolingular fossa can
be an arduous task owing to the thickness of the internal oblique ridge. Hence,
placement of horizontal osteotomy depends on the experience of the operator.Here,
the authors describe a simple, low profile instrument that aids in the
identification of the lingula as well as provide a posterior stop for horizontal
osteotomy during the sagittal split ramus osteotomy procedure.
PMID- 28692502
TI - Reconstruction of Zygomaticomaxillary Buttress With Mandibular Ramus Bone Graft
in Atrophic Maxillary Fracture.
PMID- 28692503
TI - Acquired Adult Onset Cyclic Esotropia in Patients With Myopic Strabismus Fixus
and Intraocular Lens Implantation.
AB - PURPOSE/BACKGROUND: Cyclic esotropia is a rare condition that mostly occurs in
children, characterized by patterns of straight and strabismic days with a
regular cycle of 24 to 96 hours. In this report, 2 patients of cyclic esotropia
in adults who showed a regular 48-hour cycle of mild deviation on 1 day followed
by a more severe deviation on the second day are presented. METHODS: Clinical
reports, clinical features, imaging findings, and surgical outcomes are
presented. RESULTS: In patient 1, a 42-year-old male with high myopia was
diagnosed with progressive esotropia for 2 years. A medial and lateral rectus
(LR) recession/resection was performed 9 months before. On day 1 after this
surgery, a relatively mild esotropia was present which developed into a severe
esotropia on day 2. Being diagnosed as cyclic esotropia with myopic strabismus
fixus, he underwent a 4 mm re-recession of the medial rectus combined with a half
Jensen procedure in his right eye. After the second surgery, the cyclic pattern
was no longer present. In patient 2, a 39-year-old female with high myopia had
concomitant esotropia for 20 years. At 6 months following bilateral intraocular
lens implantation for her high myopia, she demonstrated a cyclic strabismus. On
day 1, a 25 prism dioptres esotropia was present, which increased to a 45 prism
diopters esotropia on day 2. A 4 mm recession of the medial rectus and 6 mm
resection of the LR was performed in her left eye. After surgery, the cyclic
pattern disappeared. CONCLUSIONS: Cyclic esotropia can occur in adults with
myopic strabismus fixus subjected to horizontal strabismus surgery and with
concomitant strabismus following intraocular lens implantation for high myopia.
Their cyclic strabismus consisted of a mild squint on day 1 which increased in
severity on day 2. The extent of surgery required for correction was based upon
the "severe esotropia" experienced on day 2 and resulted in an excellent
therapeutic outcome.
PMID- 28692504
TI - The Effect of External Approach Septoplasty on Olfactory Function.
AB - OBJECTIVE: Septal deviation-induced nasal obstruction is frequently accompanied
by hyposmia. The aim of this study was to evaluate the effect of external
approach septoplasty on olfactory function. METHODS: Thirty patients (23 males, 7
females) who had external approach septoplasty were included in the study. The
age interval was 18 to 60 years (mean 33+/-12 years). All subjects had olfactory
function and acoustic rhinometry tests in both the pre- and postoperative periods
(mean interval 6 weeks +/- 3 weeks). Olfactory function was determined by the
"Sniffin Sticks" test. The minimum cross-sectional area from the nostril to 2.20
cm backward was referred to as MCA1, and the minimum cross-sectional area from
2.20 to 5.40 cm was referred to as MCA2, determined by acoustic rhinometry.
RESULTS: Olfactory threshold, discrimination, and identification function
improved significantly after external approach septoplasty. A statistically
significant difference was also detected between pre- and postoperative left MCA1
and left MCA2 of the nasal cavities. Postoperative hyposmic and anosmic patient
improvement was statistically significant. CONCLUSION: External approach
septoplasty has a beneficial effect on olfaction and this effect may be partly
due to interactions between the increased perception of nasal air flow, as well
as surgery-associated improvement in the internal nasal valve area.
PMID- 28692505
TI - Presurgical Orthopedic Treatment Using Modified Nostril Retainers in Patients
With Unilateral Cleft Lip With or Without Cleft Palate.
AB - This study aimed to present a new technique for presurgical orthopedic treatment
of patients with unilateral cleft lip with or without cleft palate (UCL+/-P) by
means of modified nostril retainers manufactured using a special mold with soft
acrylic or orthodontic acrylics material. Nasal molding with the modified nostril
retainer is considerably effective and comfortable for the patient.
PMID- 28692506
TI - Reduction of Surgical Site Infections After Cranioplasty With Perioperative
Bundle.
AB - BACKGROUND: Surgical site infections (SSI) are the most common complication after
cranioplasty and it is associated with poor prognosis. The aim of this study was
to identify the risk factors that triggered the development of SSI after
cranioplasty and establish a new perioperative bundle and monitoring system to
reduce SSI. METHODS: A retrospective review of a database that included all
cranioplasty patients from 2001 to 2007 was carried out to determine the
prevalence of infection. A surveillance team was set up, which assessed the
clinical practice and led to the development of a new perioperative bundle and
supervision system. A prospective study between 2008 and 2014 was carried out to
observe whether infection rates had changed and whether an active surveillance
program can change clinical practice. RESULTS: Retrospective period included 86
adult patients. The overall rate of infection was 10.5% (9 SSI in 86 patients).
Age >=60 years (OR 1.05; 95% CI: 1.00-1.10; P = 0.04), smoking (OR 9.13; 95% CI:
1.65-50.60; P = 0.01), and duration of operation >=180 minutes (OR1.19; 95% CI:
1.06-1.34; P < 0.01) as significant predictors of postcranioplasty SSI
development. Length of preoperative stay and length of hospitalization was
significantly longer among infected patients compared with uninfected patients (P
< 0.01, respectively). In prospective period, the general SSI rate was reduced to
1.8% (2 SSI in 113 patients). The difference was statistically significant (P =
0.01). CONCLUSIONS: A perioperative bundle and monitoring system may help to
reduce SSI rates after cranioplasty. This work also indicates how an active
surveillance program can successfully change clinical practice.
PMID- 28692507
TI - Eagle Syndrome: a Follow-Up Examination of Four Patients After Surgical Treatment
Via Cervical Approach.
AB - OBJECTIVE: Eagle syndrome is a rare pain syndrome caused by an elongated styloid
apophysis or an ossified styloid ligament. It is characterized by a complex range
of symptoms in head and neck region. The most effective treatment is surgical
shortening of the styloid apophysis. The authors report of a follow-up
examination of 4 patients after surgical treatment via cervical approach.
METHODS: Retrospectively reviewed hospital records of 5 patients (4 females and 1
male), aged from 26 to 59 years old (mean age = 45.5 years) who underwent
surgical shortening of the styloid process via cervical approach. Further, a
paper-based survey of 4 patients was conducted, including a clinical
questionnaire and 4 visual analogue scales, consisting of questions regarding
postoperative pain. RESULTS: Period of follow-up ranged from 16 to 79 months
(mean 53.75 months). All patients were asymptomatic at follow-up. None of the
patients reported a visible scar or hypoesthesia in the affected area. The
patients demonstrated low mean visual analogue scales for each item (facial pain:
0.6 +/- 1.2, foreign body sensation: 0.725 +/- 1.45, pain of throat and neck 1.35
+/- 1.58 and limitation of dietary habits: 0.75 +/- 1.5). None of the patients
reported a resurgence of pain in the head and neck region so far. CONCLUSIONS:
Surgical treatment via cervical approach appears to be an effective and safe
option with low morbidity and mortality in the treatment of symptomatic Eagle
syndrome of adults.
PMID- 28692508
TI - Effect of Cervical Siphon of External and Internal Carotid Arteries.
AB - Variant courses, configuration, and branching pattern of the external and
internal carotid arteries, especially when curved in S-shape, are important for
hemodynamic changes and clinical implications. Therefore, the aim of the study is
to report abnormal cervical siphons observed in external and internal carotid
arteries to explore clinical significance by review of literature and hemodynamic
changes theoretically.The right common carotid artery bifurcated into external
and internal carotid arteries at the level of the upper border of thyroid
cartilage in a 70-year-old female cadaver. After bifurcation, the external
carotid artery underwent severe tortuosity coursing through 5 bends at points A,
B, C, D, and E from its origin to termination and 2 bends at A' and B' in
internal carotid artery in the cervical region. The angles between inflow and out
flow of the blood at the bends were measured and the change in velocity at each
bend was computed for both arteries. Hemodynamic changes were calculated,
compared and relevant clinical complications were theoretically correlated.The
angles of 20 degrees , 30 degrees , 51 degrees , 52 degrees , 60 degrees , and 28
degrees , 48 degrees were formed by 5 bends of external and 2 bends of internal
carotid arteries, respectively. The curved courses of these arteries caused
reduction in velocity/stasis, turbulence, and low shear stress. Such kinks might
cause stroke, ischemia and mistaken for tumors and abscess in imagery leading to
or otherwise producing iatrogenic repercussions. This study will be useful for
anatomists, clinicians, and radiologists.
PMID- 28692509
TI - Stepwise, Multi-Incisional, and Single-Stage Approach to Reshape Facial Contour
After Large Cutaneous Lesion Resection.
AB - BACKGROUND: Removal of large facial benign cutaneous lesions remains challenging.
Serial or complete excisions together with local flaps or expander-based
reconstructions are required. However, those techniques are time-consuming and
may contribute to poor cosmetic and functional outcomes. OBJECTIVE: The authors
describe the resection and reconstruction of large facial benign cutaneous
lesions by using Stepwise, Multi-Incisional, and Single-Stage (SMISS) approach.
METHODS: The authors performed a retrospective review from all patients with
large facial benign cutaneous lesions who underwent "SMISS" approach for
reconstruction between September 2013 and December 2014. RESULTS: The authors
treated 47 patients (32 female and 15 male; mean age 23.5 years, range 9-50
years). Follow-up was for 12 months or longer. The mean length of major axis was
43.91 mm, minor axis 32.10 mm, and scar 66.91 mm. Good to excellent outcomes were
achieved in all patients with a mean Vancouver scar scale score of 3.46 +/- 0.39
(Cronbach alpha = 0.890) and mean visual analog scale score of 8.02 +/- 0.69
(Cronbach alpha = 0.946). LIMITATIONS: This was a nonrandomized, unblinded
clinical case series with a limited sample size. CONCLUSION: For the excision and
reconstruction of large facial benign cutaneous lesions, "SMISS" technique can be
considered as a suitable option, leading to excellent results and a high patient
satisfaction.
PMID- 28692510
TI - Giant Serpentine Middle Cerebral Artery Aneurysm.
AB - Giant serpentine aneurysms are rare entity, which have unique presentations and
distinct angiographic features, with poor prognosis if not treated. In this
paper, a patient with a giant serpentine aneurysm originated from right middle
cerebral artery was reported. A 38-year-old woman suffered from progressively
headache and vision declined. The computed tomography and magnetic resonance
image revealed a partially calcified, large mass (approximately 80 * 70 * 60 mm
sized) in the right frontal-temple lobe. On computed tomography angiography, an
unruptured, giant, partially thrombosed, serpentine aneurysm was confirmed. After
treatment by craniotomy, the patient was rehabilitation. Operation is an
effective method for the treatment of giant serpentine aneurysms. In addition,
cerebral angiography and balloon test occlusion are the crucial way of
preoperative assessment.
PMID- 28692511
TI - An Unusual Bullet Trajectory: Entered Through the Face and Ended Up in the Neck.
AB - The authors describe a case of gunshot injury in a 26-year-old male patient with
an unusual bullet trajectory. The bullet had an entry hole just near the right
lateral alar cartilage of the nose, and the trajectory descended through the left
side of the neck by route of the hard palate, soft palate, and posterior
pharyngeal wall, respectively. Surgical removal of the bullet was achieved with
neck exploration. Gunshot injuries of the head and neck necessitate a thorough
clinical and radiological evaluation due to the possibility of an unusual bullet
trajectory.
PMID- 28692512
TI - Role of Notch Signaling in the Physiological Patterning of Posterofrontal and
Sagittal Cranial Sutures.
AB - BACKGROUND: The mutations in a Notch signaling ligand, jagged 1, are associated
with unilateral coronal craniosynostosis in humans. However, the underlying
mechanisms of Notch signaling in cranial suture biology still remain unclear.
METHODS: The temporal and spatial patterns of Notch signaling expression were
examined in the posterofrontal and sagittal sutures of Sprague-Dawley rats by
real-time quantitative reverse-transcription polymerase chain reaction at
postnatal ages of 2, 15, and 25 days. The role of Notch signaling in the
proliferation and differentiation of osteoblasts isolated from calvarial was
examined in vitro by EdU incorporation assays and real-time quantitative reverse
transcription polymerase chain reaction after activating and inhibiting Notch
signaling. RESULTS: The mRNA levels of Notch family members (including Jagged 1,
Delta 1, 3, 4, Notch 1-4, Hes 1, and Hes 5) decreased during the posterofrontal
cranial suture fusion in rat. However, in the patent sagittal sutures, the mRNA
levels of Notch family members (Jagged 2, Delta 1, Notch 1, Notch 3, Hes 5, and
Hey 1) increased during suture development. The EdU incorporation assays revealed
that the induction of Notch signaling in calvaria osteobalsts using Jagged 1
promoted the proliferation rates in those cells in vitro. Further studies showed
that activation of Notch signaling calvaria osteobalsts using Jagged 1 led to the
suppression of late osteogenetic markers such as type I collagen and osteocalcin.
CONCLUSIONS: The regulation of Notch signaling is of crucial importance during
the physiological patterning of posterofrontal and sagittal cranial sutures.
Thus, targeting this pathway may prove significant for the development of future
therapeutic applications in craniosynostosis.
PMID- 28692513
TI - Viability and Biomechanics of Diced Cartilage Blended With Platelet-Rich Plasma
and Wrapped With Poly (Lactic-Co-Glycolic) Acid Membrane.
AB - OBJECTIVES: The objective of this study was to investigate the viability and
biomechanics of diced cartilage blended with platelet-rich plasma (PRP) and
wrapped with poly (lactic-co-glycolic) acid (PLGA) membrane in a rabbit model.
METHODS: A total of 10 New Zealand rabbits were used for the study. Cartilage
grafts were harvested from 1 side ear. The grafts were divided into 3 groups for
comparison: bare diced cartilage, diced cartilage wrapped with PLGA membrane, and
diced cartilage blended with PRP and wrapped with PLGA membrane. Platelet-rich
plasma was prepared using 8 mL of auricular blood. Three subcutaneous pockets
were made in the backs of the rabbits, and the grafts were placed in these
pockets. The subcutaneous implant tests were conducted for safety assessment of
the PLGA membrane in vivo. All of the rabbits were sacrificed at the end of 3
months, and the specimens were collected. The sections were stained with
hematoxylin and eosin, toluidin blue, and collagen II immunohistochemical.
Simultaneously, biomechanical properties of grafts were assessed. RESULTS: This
sample of PLGA membrane was conformed to the current standard of biological
evaluation of medical devices. Moderate resorption was seen at the end of 3
months in the gross assessment in diced cartilage wrapped with PLGA membrane,
while diced cartilage blended with PRP had no apparent resorption macroscopically
and favorable viability in vivo after 3 months, and the histological parameters
supported this. Stress-strain curves for the compression test indicated that the
modulus of elasticity of bare diced cartilage was 7.65 +/- 0.59 MPa; diced
cartilage wrapped with PLGA membrane was 5.98 +/- 0.45 MPa; and diced cartilage
blended with PRP and wrapped with PLGA membrane was 7.48 +/- 0.55 MPa,
respectively. CONCLUSIONS: Diced cartilage wrapped with PLGA membrane had
moderate resorption macroscopically after 3 months. However, blending with PRP
has beneficial effects in improving the viability of diced cartilages.
Additionally, the compression modulus of diced cartilage blended with PRP and
wrapped with PLGA membrane was similar to bare diced cartilage.
PMID- 28692514
TI - Application of Bidirectional Distraction Osteogenesis for the Treatment of
Mandibular Micriognathia Caused by Temporomandibular Joint Ankylosis.
AB - BACKGROUND: Temporomandibular joint (TMJ) ankylosis is a joint disorder that
refers to bone or fibrous adhesion of the anatomic joint components and the
ensuing loss of function. When it happens on children, it is always accompanied
by dentofacial deformities. The objective of this study was to describe the
authors' experience of bidirectional distraction osteogenesis for the treatment
of mandibular deformities caused by TMJ ankylosis. METHODS: Sixteen patients with
TMJ ankylosis and severe secondary mandibular deformities were treated with
bidirectional distraction osteogenesis and release of joint from January 2013 to
December 2015. Clinical outcomes were assessed based on the oral function,
radiography, and medical photography. RESULTS: No reankylosis was found during
the follow-up period. Sufficient volume and density new bone had been formed
after the consolidation period. All patients have maintained stable improvement
in oral function during the follow-up period. Most of the patients achieved
satisfactory outcomes. CONCLUSIONS: Bidirectional transport distraction
osteogenesis technique is a good and effective therapeutic option in treatment of
bilateral or unilateral TMJ ankylosis patients associated with mandibular
micrognathia.
PMID- 28692515
TI - Criteria for Performing Cranial Computed Tomography for Chinese Patients With
Mild Traumatic Brain Injury: Canadian Computed Tomography Head Rule or New
Orleans Criteria?
AB - Computed tomography (CT) provides the primary diagnostic evidence for traumatic
brain injury (TBI), but few positive traumatic findings are discovered in
patients with mild TBI. In China, there are no existing criteria for selecting
patients with mild TBI to undergo CT, and almost all of these patients undergo
cranial CT in the emergency department. This retrospective study was performed to
evaluate the necessity of cranial CT among patients with mild TBI, as well as the
feasibility of 2 popular criteria (Canadian CT head rule [CCHR] and New Orleans
Criteria [NOC]) in China. Patients with mild TBI who underwent cranial CT within
24 hours of the trauma were included in our institute. Two neurosurgeons reviewed
the CT images independently to identify positive CT findings. The sensitivity and
specificity of CCHR and NOC for positive CT findings related to TBI were
analyzed. Finally, this study included 625 patients. Positive CT findings related
to TBI were discovered in 13.12% (82/625) of these patients on cranial CT, and
6.88% (43/625) of them were admitted to the hospital for further management.
Ultimately, 11 patients (1.76%, 11/625) underwent neurosurgery. In this study,
the sensitivities of both the CCHR and NOC were 100%, but the specificity of CCHR
was 43.36% and that of NOC was 33.12%. Based on our study, both CCHR and NOC have
high sensitivity for the detection of positive CT findings related to head trauma
in patients with mild TBI.
PMID- 28692516
TI - Clinical Application of the Pedicled Buccal Fat Pad Flap in Immediate
Reconstruction of Oral Tissue Defects in Oral Surgery.
AB - OBJECTIVE: The aim of this study was to present a new immediate reconstructive
option for oral tissue defects with a pedicled buccal fat pad flap in oral
surgery. MATERIALS AND METHODS: Fifteen cases (10 males, 5 females; mean age: 50
years) suffering from oral tumor and attending the Affiliated Stomatology
Hospital of Kunming Medical University were included in this study. All patients
underwent immediate repair surgery involving a pedicled buccal fat pad graft in
oral surgery, from July 2013 to August 2016. RESULTS: All cases underwent
uneventful healing with a surviving graft flap. The buccal fat pad healed in
about 9 to 10 weeks and its uncovered surface became epithelialized with similar
feature to the normal mucosa. At a follow-up of 3 months to 3 years, a good
outcome was obtained with minimal malfunction and face deformity. CONCLUSIONS:
The pedicled buccal fat pad is ideal material for repair, and it is a viable
option for immediate reconstruction of oral tissue defects in oral surgery.
PMID- 28692517
TI - Resection of Adenoid Cystic Carcinoma Originating From the Cavernous Sinus Via
Endoscopic Endonasal Approach.
AB - A 50-year-old woman presented with gradually increasing right-sided facial
numbness. Neuroimaging revealed a lesion in the right cavernous sinus mimicking
meningioma. The resection of the right cavernous sinus neoplasm was implemented
via endoscopic endonasal approach under general anesthesia. Histological
examination of the surgical specimen revealed adenoid cystic carcinoma. Adenoid
cystic carcinoma in the cavernous sinus is extremely rare as a primary lesion and
challenging to manage. Little data exist to guide treatment when this tumor
extends to involve the structure of cavernous sinus. Our study illustrates that
endoscopic endonasal approach is a good choice for resection of the tumor in the
cavernous sinus.
PMID- 28692518
TI - Costal Cartilage Assessment in Surgical Timing of Microtia Reconstruction.
AB - BACKGROUND: Rib cartilage growth is closely related to age and determines the
feasibility and outcomes of auricular reconstruction. Ear reconstruction is
performed as early as age 6 in efforts to treat children before school
matriculation while allowing for sufficient rib growth. But there is controversy
over the optimal timing of microtia reconstruction. This study employs CT imaging
and surface scanning to guide the timing of auricular reconstruction in children.
METHODS: A retrospective analysis was performed on 6-year-old microtia patients
between January 2016 and June 2016. A total of 37 patients were underwent
preoperative 3D rib-cage CT measurements and normal auricle scanning measurement
including: the length of 6th, 7th, and 8th costal cartilage, the width of 6th,and
7th costal cartilage, and the length of normal auricle. Then the data of costal
cartilage were compared with the data of the auricle. RESULTS: The average length
of the 6th, 7th, and 8th rib cartilage on the right was 76.1 +/- 9.2 mm (range,
61.1-94.9 mm), 102.6 +/- 9.9 mm (range, 84.5-119.1 mm), and 75.4 +/- 19.3 mm
(range, 47.3-118.5 mm), respectively, and the the average helical length was 90.5
+/- 6.8 mm (range, 76.9-101.5 mm). Comparing the above data, it was revealed that
the age of 6 years was an optimal time for ear reconstruction with tissue
expanding technique. CONCLUSIONS: 3D rib-cage CT for preoperative measurement of
costal cartilage could be a useful method for planning microtia reconstruction.
According to our study, the amount of costal cartilage of almost all 6-year-old
microtia patients is enough for ear reconstruction. So age 6 years is the optimal
timing of auricular reconstruction with tissue-expanding method.
PMID- 28692519
TI - Intralesional Lidocaine Anesthesia: A Novel Facilitated Anesthesia Technique for
Ethanol Sclerotherapy of Venous Malformation.
AB - OBJECTIVE: The aim of this study was to describe a novel anesthesia,
intralesional lidocaine anesthesia (ILA), for ethanol sclerotherapy of venous
malformation and evaluate the efficacy and safety. METHODS: A prospective study
of 100 patients with venous malformations undergoing 100 sclerotherapy procedures
with intralesional lidocaine anesthesia (ILA) was conducted. Pain was evaluated
by numeric rating scale (NRS) immediately following the procedure. The grade of
pain was classified by the NRS as no pain (0), mild (1-3), moderate (4-6), and
severe (7-10). Local and systemic complications caused by lidocaine were
recorded. RESULTS: The median injected volume of absolute ethanol and 0.25%
lidocaine was 5.9 mL and 17.0 mL, respectively. In ILA group, 13 patients had no
pain during the procedure, 42 patients had mild pain, 38 patients had moderate
pain, and 7 patients had severe pain. The mean NRS scores of the whole ILA group
were 3.2 (0-8). No local or systemic complications attributed to lidocaine were
reported. CONCLUSION: In a limited series, intralesional lidocaine anethesia
seems to be efficient and safe for use in pain management for ethanol
sclerotherapy of venous malformation. This anesthesia technique may be a
promising first approach for the ethanol sclerotherapy of venous malformations,
as it is easy to handle and has minimal sequelae.
PMID- 28692521
TI - Evaluation Intravenous Drip Cephazolin Prophylaxis of Breast Cancer Surgery Site
Infection.
AB - PURPOSE: The efficacy of antibiotic prophylaxis for the prevention of surgical
site infection (SSI) after breast cancer surgery remains uncertain. The authors
of a recent Cochrane meta-analysis based on 15 randomized trials were unable to
draw a definitive conclusion. The purpose of this study was to determine the
effectiveness of prophylactic antibiotics for the prevention of SSI after breast
cancer surgery and the risk factors for SSI. METHODS: Breast cancer patients who
underwent mastectomy at the authors' institution were enrolled in this study. All
the patients give cephazolin by intravenous drip within 1 hour before surgery.
Surgical site infection was defined using Centers for Disease Control criteria.
Risk factors were abstracted from the electronic medical record. Pearson chi
test, Student t test, and multivariable logistic regression were used for the
analysis. RESULTS: Four hundred fifty-eight patients undergoing mastectomy were
enrolled in this study, including 293 with intravenous drip cephazolin and 165
without. Among them, an overall SSI rate of 6.1% was observed; 4.2% of patients
without prophylactic antibiotics developed SSI compared with 7.2% with
antibiotics (P = 0.210). Factors associated with SSI were hypertension, diabetes,
length of stay (d), age, and length of stay. Weight, duration of surgery, No. of
drains, surgical procedure, and type of breast disease were not associated with
increased SSI rates. CONCLUSIONS: Surgical site infection rates among patients
who did and did not receive cephazolin after mastectomy had no significantly
different. What is more, the authors should focus on advanced age, hypertension,
diabetes, length of stay, and length of stay to decrease development of
postoperative SSI rates.
PMID- 28692522
TI - Reconstructive Operation of Nonsyndromic Multiple-Suture Craniosynostosis Based
on Precise Virtual Plan and Prefabricated Template.
AB - This report presents a case of a 4-year-old girl suffering from multiple-suture
nonsyndromic craniosynostosis. The patient is characterized with fronto-orbital
malformation and poor visual acuity. The preoperational three-dimensional
computed tomography scan showed premature closure of the sagittal suture,
bilateral coronal, and lambdoidal suture. The virtual surgical planning was
performed before operation for the reposition of bone segments and communication
with the patient's family. The navigational plate for reshaping was made based on
the surgical plan with three-dimensional printed model. Both visual acuity and
the fronto-orbital morphology were improved at 1 year follow-up. The authors
believed that multiple-suture nonsyndromic craniosynostosis should be treated as
early as possible to protect the brain and eyes. It can improve the safety and
precision of the treatment using the virtual surgical planning and prefabricated
surgical template.
PMID- 28692523
TI - The Prognosis Factors for Endovascular Coiling of Aneurysm in Patients With
Ruptured Intracranial Aneurysm.
AB - BACKGROUND: The spontaneous subarachnoid hemorrhage caused by aneurysm rupture
often leads to a variety of complications. Endovascular coiling is effective in
the treatment of ruptured intracranial aneurysm. AIM: The authors aim to evaluate
the risk factors affecting the prognosis of ruptured intracranial aneurysm in
patients who received endovascular coiling treatment successfully. METHODS: The
demographic and clinical data including age, gender, blood pressure, blood
glucose, Hunt-Hess grade, and Fisher grade at admission, Glasgow outcome scale 3
months after coiling, and the location, size of the aneurysms, coiling methods,
and time of intervention were retrospectively reviewed and analyzed. Multivariate
analysis and logistic regression were used for data analysis. RESULTS: The
history of diabetes mellitus, Hunt-Hess grade, Fisher classification at
admission, timing of intervention, as well as the location and size of the
aneurysm were prognostic factors for endovascular coiling therapy in patients
with ruptured intracranial aneurysm. CONCLUSION: The Fisher scores, Hunt-Hess
classification, history of diabetes mellitus, timing of the intervention, as well
as the location and size of aneurysm were independent risk factors for ruptured
intracranial aneurysms in patients who received endovascular coiling treatment
successfully, which could highly affect the outcome of coiling therapy.
PMID- 28692524
TI - Monofocal Chronic Nonbacterial Osteomyelitis in the Mandible Accompanied With
Mucocutaneous Disease.
AB - Chronic nonbacterial osteomyelitis (CNO) is a bone disease with nonbacteria
osteitis of unknown etiology. Symptoms, including pain, swelling, fever, etc,
always result in misdiagnosis and wrong therapy. This study aims to introduce the
clinical features and the therapy of patients with CNO accompanied with
mucocutaneous disease. The authors retrospectively reviewed the patients who
presented to our hospital from 2000 to 2016, the final sample including 3
patients with CNO accompanied with mucocutaneous disease, who presented repeated
severe pain of bone, swelling, tenderness, and fever during attack stage with no
evidence of bacterial infections. One patient underwent surgery, and all of them
took the therapy of nonsteroidal anti-inflammatory drugs and immunosuppressive
agents. There was no significant effect after taken surgery, but good results
with drugs. The study suggested us that medical therapy sometimes better than
surgery in CNO accompanied with mucocutaneous disease.
PMID- 28692525
TI - Effect of Adjuvant Chemotherapy on Left Ventricular Remodeling in Women with
Newly Diagnosed Primary Breast Cancer: A Pilot Prospective Longitudinal Cardiac
Magnetic Resonance Imaging Study.
AB - PURPOSE: The aim of this study was to assess the left ventricular (LV) remodeling
response to chemotherapy in low-cardiac-risk women with newly diagnosed
nonmetastatic breast cancer. Cardiotoxic effects of chemotherapy are an
increasing concern. To effectively interpret cardiac imaging studies performed
for screening purposes in patients undergoing cancer therapy it is necessary to
understand the normal changes in structure and function that may occur. METHODS:
Twenty women without preexisting cardiovascular disease, of a mean age of 50
years, newly diagnosed with nonmetastatic breast cancer and treated with
anthracycline or trastuzumab, were prospectively enrolled and evaluated at four
time points (at baseline, during chemotherapy, 2 weeks after chemotherapy, and 6
months after chemotherapy) using cardiac magnetic resonance imaging, blood
samples, and a clinical questionnaire. RESULTS: Over a 6-month period, the left
ventricular ejection fraction (%) decreased (64.15+/-5.30 to 60.41+/-5.77,
P<0.002) and the LV end-diastolic (mm) and end-systolic (mm) volumes increased
(124.73+/-20.25 to 132.21+/-19.33, P<0.04 and 45.16+/-11.88 to 52.57+/-11.65,
P<0.00, respectively). The LV mass (g) did not change (73.06+/-11.51 to 69.21+/
15.3, P=0.08), but the LV mass to LVEDV ratio (g/mm) decreased (0.594+/-0.098 to
0.530+/-0.124, P<0.04). CONCLUSIONS: In low-cardiac-risk women with nonmetastatic
breast cancer, the increased LV volume and a mildly decreased left ventricular
ejection fraction during and after chemotherapy do not seem to be associated with
laboratory or clinical evidence of increased risk for heart failure.
PMID- 28692526
TI - Preoperative Nutritional Assessment with the Prognostic Nutrition Index in
Patients Undergoing Left Ventricular Assist Device Implantation.
AB - The prognostic nutritional index (PNI) is a simple metric that uses serum albumin
and total lymphocyte count to provide a basic indicator for nutritional status.
It has recently garnered attention as a prognosticator of outcomes in many types
of cancer. We investigated the utility of the PNI as a marker for poor outcomes
following left ventricular assist device (LVAD) implantation. Two hundred eighty
eight consecutive patients implanted with continuous-flow LVADs were included.
Prognostic nutritional index was calculated for all patients (PNI = [10 * serum
albumin {g/dl}] + [0.005 * total lymphocytes {1,000/MUl}]). The population was
split into two groups based on median PNI; group 1 with PNI <30 and group 2 with
PNI >=30. Mean age was 60.3 years in group 1 and 59.8 years in group 2. There
were no significant differences between groups in terms of age, gender,
ethnicity, or comorbidities. The mean PNI for the group as a whole was 30.1 +/-
4.6, indicating pervasive malnutrition in this group of advanced heart failure
patients. Group 1 had significantly longer postoperative length of stay than did
group 2 (27.42 +/- 19.31 vs. 21.66 +/- 15.0 days; p = 0.008). Patients in group 1
also had higher rates of right ventricular failure (37.8% vs. 25.5%; p = 0.025).
A multivariate model indicated that PNI less than 30 was associated with a 12.2%
reduction in postoperative survival (Hazard Ratio: 0.888; confidence interval
[CI]: 0.795-0.993; p = 0.037). Our results suggest that the PNI may be an
indicator for worsened outcomes in patients with advanced heart failure. These
patients, who often suffer from chronic malnutrition, may experience worsened
outcomes because of associated neurohormonal, muscular, and metabolic
derangements.
PMID- 28692528
TI - Editorial: a viewpoint on European standards for neuromuscular training,
qualification, and certification.
PMID- 28692527
TI - Sildenafil in Left Ventricular Assist Device Is Safe and Well-Tolerated.
AB - Right heart failure is a potentially devastating complication of mechanical
circulatory support, occurring at a rate of 0.49 events per 100 patient-months.
Pulmonary vasodilators such as phosphodiesterase-5 inhibitors (PDE5i) have been
frequently used to unload the right ventricle in left ventricular assist device
(LVAD) patients, but there is scant evidence to support this practice., The
purpose of this analysis is to provide additional data regarding the safety and
efficacy of the PDE5i sildenafil in a real world population of patients supported
with LVADs at Washington University in St. Louis. Sildenafil use was not
associated with differences in gastrointestinal (GI) bleeding, stroke, mortality,
heart failure (HF) admission, or orthotopic heart transplantation (OHT).
PMID- 28692529
TI - CYP2B6 genotypes and early efavirenz-based HIV treatment outcomes in Botswana.
AB - OBJECTIVES: To determine the association between cytochrome p450 2B6 genotypes
and efavirenz-based HIV treatment outcomes. DESIGN: Observational cohort study of
HIV-infected adults initiating efavirenz-based regimens in Botswana. METHODS: The
primary endpoint was a composite of death or loss to care or HIV RNA more than 25
copies/ml at 6 months. CYP2B6 516G>T and 983T>C genotyping was done with Taqman
Open Array platform. Adverse experiences were measured by using the Subject
Experience Questionnaire. Metabolism alleles were included in logistic regression
models of the composite endpoint. RESULTS: A total of 801 individuals included
406 (51%) men, median age 37 years, median baseline CD4 cell count 195 cells/MUl,
and plasma HIV RNA 4.9 log10 copies/ml. 288 (36%) reached the endpoint, including
34 (4%) deaths, 151 (19%) lost to care, 11 (1%) lost to the study, but alive and
in care, and 92 (11%) with plasma HIV RNA more than 25 copies/ml. Metabolism
variant alleles were common with 396 (49%) intermediate and 192 (24%) slow
metabolizers. There were no statistically significant associations between
metabolism and treatment endpoints. However, slower metabolism was associated
with fewer adverse experiences. CONCLUSION: Slow metabolism alleles were
associated with lower efavirenz clearance but not any of the treatment endpoints.
Slow efavirenz metabolism did not exacerbate central nervous system toxicity.
These results should allay concern that slow efavirenz metabolism adversely
impacts individuals in sub-Saharan African settings in which these alleles are
common.
PMID- 28692530
TI - Limited overlap between phylogenetic HIV and hepatitis C virus clusters
illustrates the dynamic sexual network structure of Dutch HIV-infected MSM.
AB - OBJECTIVE: MSM are at increased risk for infection with HIV-1 and hepatitis C
virus (HCV). Is HIV/HCV coinfection confined to specific HIV transmission
networks? DESIGN AND METHODS: A HIV phylogenetic tree was constructed for 5038
HIV-1 subtype B polymerase (pol) sequences obtained from MSM in the AIDS therapy
evaluation in the Netherlands cohort. We investigated the existence of HIV
clusters with increased HCV prevalence, the HIV phylogenetic density (i.e. the
number of potential HIV transmission partners) of HIV/HCV-coinfected MSM compared
with HIV-infected MSM without HCV, and the overlap in HIV and HCV phylogenies
using HCV nonstructural protein 5B sequences from 183 HIV-infected MSM with acute
HCV infection. RESULTS: Five hundred and sixty-three of 5038 (11.2%) HIV-infected
MSM tested HCV positive. Phylogenetic analysis revealed 93 large HIV clusters
(>=10 MSM), 370 small HIV clusters (2-9 MSM), and 867 singletons with a median
HCV prevalence of 11.5, 11.6, and 9.3%, respectively. We identified six large HIV
clusters with elevated HCV prevalence (range 23.5-46.2%). Median HIV phylogenetic
densities for MSM with HCV (3, interquartile range 1-7) and without HCV (3,
interquartile range 1-8) were similar. HCV phylogeny showed 12 MSM-specific HCV
clusters (clustersize: 2-39 HCV sequences); 12.7% of HCV infections were part of
the same HIV and HCV cluster. CONCLUSION: We observed few HIV clusters with
elevated HCV prevalence, no increase in the HIV phylogenetic density of HIV/HCV
coinfected MSM compared to HIV-infected MSM without HCV, and limited overlap
between HIV and HCV phylogenies among HIV/HCV-coinfected MSM. Our data do not
support the existence of MSM-specific sexual networks that fuel both the HIV and
HCV epidemic.
PMID- 28692531
TI - Efavirenz decreases etonogestrel exposure: a pharmacokinetic evaluation of
implantable contraception with antiretroviral therapy.
AB - OBJECTIVES: The primary objective of this study was to characterize the
pharmacokinetics of etonogestrel (ENG) released from a contraceptive implant in
Ugandan women living with HIV who were receiving efavirenz (EFV) or nevirapine
(NVP)-based antiretroviral therapy (ART), compared with ART-naive women over 24
weeks. DESIGN: Nonrandomized, parallel-group study with three arms: ART-naive,
NVP, or EFV-based ART (N = 20/group). METHODS: Sparse pharmacokinetic sampling of
ENG, NVP, or EFV were performed at screening, entry, and then 1, 4, 12, and 24
week postimplant insertion. The primary endpoint was ENG concentrations at week
24, compared between the ART-naive group and each ART group, using geometric mean
ratio (GMR) with 90% confidence intervals. RESULTS: Sixty participants competed
the 24-week study and data from 58 participants are included; one participant
each was excluded from the NVP group and EFV group because of a sample processing
error and ART nonadherence, respectively. At week 24, geometric mean ENG was 362,
341, and 66 pg/ml in the ART-naive, NVP, and EFV groups, respectively [GMR: NVP :
ART-naive 0.94 (0.90-1.01); EFV : ART-naive 0.18 (0.17-0.20)]. NVP and EFV
concentrations were lower at week 24 compared to preimplant [NVP: geometric mean
5.7 versus 6.8 mg/l, respectively, GMR 0.84 (0.83-0.85); EFV: geometric mean 3.6
versus 4.9 mg/l, respectively, GMR 0.73 (0.69-0.80)]. CONCLUSION: After 24 weeks
of combined use, ENG exposure was 82% lower in women using EFV-based ART compared
with ART-naive women. In contrast, NVP did not significantly impact ENG exposure.
These results raise concerns about reduced effectiveness of implantable
contraception for women taking EFV-based ART.
PMID- 28692532
TI - Cardiovascular outcomes among HIV-infected veterans receiving atazanavir.
AB - OBJECTIVE: Patients with HIV infection have an increased risk of cardiovascular
disease compared with uninfected individuals. Antiretroviral therapy with
atazanavir (ATV) delays progression of atherosclerosis markers; whether this
reduces cardiovascular disease event risk compared with other antiretroviral
regimens is currently unknown. DESIGN: Population-based, noninterventional,
historical cohort study conducted from 1 July 2003 through 31 December 2015.
SETTING: Veterans Health Administration hospitals and clinics throughout the
United States. PARTICIPANTS: Treatment-naive patients with HIV infection (N =
9500). ANTIRETROVIRAL EXPOSURES: Initiating antiretroviral regimens containing
ATV, other protease inhibitors, nonnucleoside reverse transcriptase inhibitors
(NNRTIs), or integrase strand transfer inhibitors (INSTIs). MAIN OUTCOME/EFFECT
SIZE MEASURES: Incidence rates of myocardial infarction (MI), stroke, and all
cause mortality within each regimen. ATV versus other protease inhibitor, NNRTI,
or INSTI covariate-adjusted hazard ratios by using Cox proportional hazards
models and inverse probability of treatment weighting. RESULTS: Incidence rates
for MI, stroke, and all-cause mortality with ATV-containing regimens (5.2, 10.4,
and 16.0 per 1000 patient-years, respectively) were lower than with regimens
containing other protease inhibitors (10.2, 21.9, and 23.3 per 1000 patient
years), NNRTIs (7.5, 15.9, and 17.5 per 1000 patient-years), or INSTIs (13.0,
33.1, and 21.5 per 1000 patient-years). After inverse probability of treatment
weighting, adjusted hazard ratios (95% confidence intervals) for MI, stroke, and
all-cause mortality with ATV-containing regimens versus all non-ATV-containing
regimens were 0.59 (0.41-0.84), 0.64 (0.50-0.81), and 0.90 (0.73-1.11),
respectively. CONCLUSION: Among treatment-naive HIV-infected patients in the
Veterans Health Administration initiating ATV-containing regimens, risk of both
MI and stroke were significantly lower than in those initiating regimens
containing other protease inhibitors, NNRTIs, or INSTIs.
PMID- 28692533
TI - Adverse events of raltegravir and dolutegravir.
AB - OBJECTIVE: To compare the frequency and risk factors of toxicity-related
treatment discontinuations between raltegravir and dolutegravir. DESIGN:
Prospective cohort study. METHODS: All antiretroviral therapy (ART)-naive and ART
experienced HIV-infected individuals from the Swiss HIV Cohort Study who
initiated raltegravir or dolutegravir between 2006 and 2015 were investigated
concerning treatment modification within the first year. RESULTS: Of 4041
patients initiating ART containing raltegravir (n = 2091) or dolutegravir (n =
1950), 568 patients discontinued ART during the first year, corresponding to a
rate of 15.5 [95% confidence interval (CI) 14.5-16.9] discontinuations per 100
patient-years. Only 10 patients on raltegravir (0.5%) and two patients on
dolutegravir (0.1%) demonstrated virologic failure. The main reason for ART
discontinuation was convenience expressed as patient's wish, physician's
decision, or treatment simplification (n = 302). Toxicity occurred in 4.3% of
patients treated with raltegravir and 3.6% with dolutegravir, respectively. In
multivariable analysis, the only independent risk factor for discontinuing ART
because of toxicity was female sex (hazard ratio 1.98, 95% CI 1.45-2.71, P <
0.001).Neuropsychiatric complaints were the most commonly reported toxic adverse
events and more frequent in the dolutegravir (n = 33, 1.7%) compared with the
raltegravir group (n = 13, 0.6%). Risk of discontinuation for neurotoxicity was
lower for raltegravir than for dolutegravir in multivariable analysis (hazard
ratio 0.46, 95% CI 0.22-0.96, P = 0.037). CONCLUSION: In this, large cohort
raltegravir and dolutegravir-containing regimen demonstrated a high virologic
efficacy. Drug toxicity was infrequent and discontinuation because of
neuropsychiatric events within the first year of treatment was only marginal
higher with dolutegravir compared with raltegravir. However, monitoring of
neurotoxic side-effects of dolutegravir is important.
PMID- 28692534
TI - Blood neuron-derived exosomes as biomarkers of cognitive impairment in HIV.
AB - OBJECTIVE: To investigate proteins associated with neuronal damage in plasma
neuron-derived exosomes (NDE) of HIV-infected study participants as a liquid
biomarker for cognitive impairment. METHODS: Plasma NDE were isolated using
precipitation and immunoadsorption with antibody to a cell surface-specific
neuronal marker. Total exosomes and NDE were enumerated, characterized, and
proteins extracted and targets quantified by ELISA. RESULTS: Plasma NDE from 23
HIV seropositive individuals of which 11 had mild cognitive impairment, and 12
HIV seronegative controls of which three had cognitive impairment were isolated.
NDE were enriched for the neuronal markers neurofilament light (NF-L) and
synaptophysin (SYP). Neuropsychologically impaired individuals had fewer NDE
compared with neuropsychologically normal study participants. NDE from
neuropsychologically impaired study participants had significantly higher levels
of high-mobility group box 1 (HMGB1), NF-L, and amyloid beta proteins compared
with neuropsychologically normal individuals. NDE HMGB1 protein significantly
decreased with age in HIV-infected individuals. CONCLUSION: Plasma NDE were
altered in several ways in HIV infection. Elevated HMGB1, NF-L, and amyloid beta
proteins could distinguish cognitive impairment. NDE contents reflect neuronal
health in 'real time' and may be useful for following cognitive impairment and
response to therapy in HIV infection.
PMID- 28692536
TI - Asymptomatic anorectal Chlamydia trachomatis and Neisseria gonorrhoeae infections
are associated with systemic CD8+ T-cell activation.
AB - BACKGROUND: Oral preexposure prophylaxis (PrEP) has been established as a pivotal
strategy in HIV prevention. However, bacterial sexually transmitted infections
(STIs), such as Chlamydia trachomatis and Neisseria gonorrhoeae, are also highly
prevalent. Although the presence of STI-related mucosal lesions is a known risk
factor for HIV acquisition, the potential increase in risk associated with
asymptomatic STIs is not completely understood. Recent data demonstrated higher T
cell activation is a risk factor for sexually acquired HIV-1 infection. We
examined the effect of asymptomatic C. trachomatis and N. gonorrhoeae anorectal
infection on systemic immune activation, potentially increasing the risk of HIV
acquisition. METHODS: We analyzed samples from participants of PrEP Brasil, a
demonstration study of daily oral emtricitabine/tenofovir disoproxil fumarate HIV
PrEP among healthy MSM, for T-cell activation by flow cytometry. We included 34
asymptomatic participants with anorectal swab for C. trachomatis and/or N.
gonorrhoeae infection, whereas negative for other STIs, and 35 controls. RESULTS:
We found a higher frequency of human leukocyte antigen DRCD38 CD8 T cells (1.5
vs. 0.9%, P < 0.005) and with memory phenotype in the group with asymptomatic C.
trachomatis and/or N. gonorrhoeae infection. Exhaustion and senescence markers
were also significant higher in this group. No difference was observed in the
soluble CD14 levels. CONCLUSION: Our findings suggest asymptomatic anorectal C.
trachomatis and/or N. gonorrhoeae increase systemic immune activation,
potentially increasing the risk of HIV acquisition. Regular screening and
treatment of asymptomatic STIs should be explored as adjuvant tools for HIV
prevention.
PMID- 28692537
TI - Early initiation of antiretroviral treatment postSIV infection does not resolve
lymphoid tissue activation.
AB - OBJECTIVE: Germinal center resident follicular helper T (TFH) cells in lymphoid
follicles are a potential sanctuary for HIV/simian immunodeficiency virus (SIV)
replication. But the dynamics of germinal centers upon early initiation of
antiretroviral therapy (ART) and their potential role in the formation of viral
sanctuaries post-SIV infection are not fully understood. DESIGN: Sequential lymph
node biopsies (n = 10) were collected from SIVmac239-infected rhesus macaques
before infection, at 5 weeks postinfection/pre-ART, 6 and 12 weeks following ART
initiation. These tissues and cells were analyzed for frequencies of TFH cells
and assignment of germinal center scores. RESULTS: Modest but significant
increases in TFH cells and hyperplastic follicles with large germinal centers
were noted during the acute phase of SIV infection (week 5/pre-ART). However, 6
weeks after ART initiation, substantial increases in germinal center TFH cells,
germinal center B cells, hyperplastic follicles with large germinal centers, and
abundant local IL-21 production were observed, whereas levels of SIV RNA and DNA
of lymph nodes had decreased to barely detectable values along with barely
detectable levels of SIV antibody-producing cells. An additional 6 weeks of ART
did not appreciably decrease germinal center TFH or germinal center scores.
CONCLUSION: Thus, although early ART rapidly controls SIV replication, it does
not regulate early lymphoid activation, which may contribute to the seeding and
magnitude of viral reservoirs.
PMID- 28692538
TI - Metabolic syndrome and obesity are the cornerstones of liver fibrosis in HIV
monoinfected patients.
AB - BACKGROUND: Metabolic syndrome (MetS) and nonalcoholic fatty liver disease have
become a common finding in HIV-infected patients. However, the severity, risk
factors and pathogenesis of liver fibrosis in this population have been poorly
documented. OBJECTIVES: To assess the impact of MetS on liver fibrosis and
analyze the association between MetS, liver fibrosis and markers of adipose
tissue and macrophage activation. METHODS: In a matched cohort of HIV-1
monoinfected patients with and without MetS, after exclusion of other causes of
liver disease, we assessed liver stiffness measurement and measured levels of
serum adipokines, homeostasis model assessment index and soluble CD163 (sCD163)
and CD14 as markers of fat, insulin resistance and macrophage/monocyte
activation, respectively. RESULTS: A total of 468 HIV-monoinfected individuals
were enrolled; 405 (203 with MetS/202 without MetS) were analyzed. Patients with
MetS were older and 49% had insulin resistance. The prevalence of significant
liver fibrosis (>=F2) was higher in patients with MetS [25.1%, 95% confidence
interval (19.3-31.2)] compared with those without MetS [7.9%, (4.6-12.5), P <
0.0001]. In multivariable analysis, obesity [odds ratio: 3.9 (95% CI 2.1-7.1)]
and homeostasis model assessment [1.1 (1.06-1.2)] were independent factors of
significant fibrosis and remained associated after adjustment on MetS. Serum
levels of adipokines and sCD163 were significantly associated with the degree of
liver fibrosis. When adjusted on MetS, leptin and sCD163 remained strongly
associated with fibrosis/cirrhosis, whereas HIV parameters and antiretroviral
therapy were not. CONCLUSION: In HIV-monoinfected patients, MetS is an important
risk factor of liver fibrosis. Adipose tissue and macrophage activation might be
key players in the development of liver fibrosis but the exact mechanisms need to
be elucidated.
PMID- 28692540
TI - Unique microRNA expression in the colonic mucosa during chronic HIV-1 infection.
AB - OBJECTIVE: Chronic HIV-1 infection leads to widespread inflammation and immune
dysregulation. The gastrointestinal mucosa, a primary site for HIV-1 replication,
is thought to play a significant role in this response. MicroRNAs (miRs) are
small noncoding RNAs that regulate gene expression, including immune activation
and inflammation. Here we investigate miR expression and function in the colonic
mucosa during HIV-1 infection. DESIGN AND METHODS: Using miR profiling, we
examined miR expression in the colonic mucosa of HIV-infected patients. These
miRs were further parsed to identify those that most likely function in HIV
related inflammation. Using bioinformatics tools, we identified potential target
genes which were confirmed using in-vitro functional testing. RESULTS: We
identified 12 miRs that were differentially expressed in the colonic mucosa of
HIV-infected patients with high versus undetectable plasma viral concentrations.
Of these, both miR-26a and miR-29a were downregulated in untreated HIV-1
infection, yet not in the colonic mucosa from inflammatory bowel disease. This
downregulation occurs within the first hours after infection. These miRs were
further shown to directly target IL-6 and STAT3, respectively, with similar
changes confirmed in an ex-vivo explant infection model. CONCLUSION: miR-26a and
miR-29a levels are decreased in the colonic mucosa during chronic HIV-1
infection, and this change may be initiated during acute infection. Both miRs de
repress the IL-6/STAT3 signaling pathway, which could contribute to increased
inflammation during infection. These miRs may represent novel therapeutic targets
for HIV-1-associated inflammation in the colonic mucosa.
PMID- 28692539
TI - HIV-hepatitis B virus coinfection: epidemiology, pathogenesis, and treatment.
AB - : HIV infection has a significant impact on the natural history of chronic
hepatitis B virus (HBV) infection, with increased levels of HBV DNA, accelerated
progression of liver disease and increased liver-associated mortality compared
with HBV monoinfection. Widespread uptake and early initiation of HBV-active
antiretroviral therapy has substantially improved the natural history of HIV-HBV
coinfection but the prevalence of liver disease remains elevated in this
population. In this paper, we review recent studies examining the natural history
and pathogenesis of liver disease and seroconversion in HIV-HBV coinfection in
the era of HBV-active antiretroviral therapy and the effects of HIV directly on
liver disease. We also review novel therapeutics for the management of HBV with a
particular emphasis on clinical strategies being developed for an HBV cure and an
HIV cure and their impact on HIV-HBV coinfected individuals.
PMID- 28692542
TI - The effect of oral preexposure prophylaxis on the progression of HIV-1
seroconversion.
AB - OBJECTIVE: To investigate whether oral preexposure prophylaxis (PrEP) alters
timing and patterns of seroconversion when PrEP use continues after HIV-1
infection. DESIGN: Retrospective testing of the timing of Fiebig stage HIV-1
seroconversion in the Partners PrEP Study, a randomized placebo-controlled
clinical trial of PrEP conducted in Kenya and Uganda. METHODS: Specimens from 138
seroconverters were collected every 3 months and when HIV-1 infection was
suspected based on monthly rapid HIV-1 tests. Progression of seroconversion was
compared between randomized groups (PrEP versus placebo) and per-protocol groups
(placebo versus PrEP participants with detectable tenofovir during the
seroconversion period) using laboratory assessment of Fiebig stage. Delay in site
detection of seroconversion and association with PrEP drug-regimen resistant
virus were assessed using logistic regression. Analysis of time to each Fiebig
stage used maximum likelihood estimation with a parametric model to accommodate
the varying lengths of HIV-infection intervals. RESULTS: There was a significant
increase in delayed site detection of infection associated with PrEP (odds ratio
= 3.49, P = 0.044). Delay in detection was not associated with increased risk of
resistance in the PrEP arm (odds ratio = 0.93, P = 0.95). Estimated time to each
Fiebig stage was elongated in seroconverters with evidence of ongoing PrEP use,
significantly for only Stage 5 (28 versus 17 days, P = 0.05). Adjusted for Fiebig
stage, viral RNA was ~2/3 log lower in those assigned to PrEP compared with
placebo; no differences were found in Architect signal to cut-off at any stage.
CONCLUSION: Ongoing PrEP use in seroconverters may delay detection of infection
and elongate seroconversion, although the delay does not increase risk of
resistance.
PMID- 28692543
TI - Impact and economic evaluation of a novel HIV service delivery model in rural
Malawi.
AB - OBJECTIVE: We performed an impact and cost-effectiveness analysis of a novel HIV
service delivery model in a high prevalence, remote district of Malawi with a
population of 143 800 people. DESIGN: A population-based retrospective analysis
of 1-year survival rates among newly enrolled HIV-positive patients at 682 health
facilities throughout Malawi, comparing facilities implementing the service
delivery model (n = 13) and those implementing care-as-usual (n = 669). METHODS:
Through district-level health surveillance data, we evaluated 1-year survival
rates among HIV patients newly enrolled between July 2013 and June 2014 -
representing 129 938 patients in care across 682 health facilities - using a
multilevel modeling framework. The model, focused on social determinants of
health, was implemented throughout Neno District at 13 facilities and compared
with facilities in all other districts. Activity-based costing was used to
annualize financial and economic costs from a societal perspective. Incremental
cost-effectiveness ratios were expressed as quality-adjusted life-years gained.
RESULTS: The national average 1-year survival rate for newly enrolled
antiretroviral therapy clients was 78.9%: this rate was 87.9% in Neno District,
compared with 78.8% across all other districts in Malawi (P < 0.001; 95%
confidence interval: 0.079-0.104). The economic cost of receiving care in Neno
district (n = 6541 patients) was $317/patient/year, compared with an estimated
$219/patient in other districts. This translated to $906 per quality-adjusted
life-year gained. CONCLUSION: Neno District's comprehensive model of care,
featuring a strong focus on the community, is $98 more expensive per capita per
annum but demonstrates superior 1-year survival rates, despite its remote
location. Moreover, it should be considered cost-effective by traditional
international standards.
PMID- 28692544
TI - The effect of school attendance and school dropout on incident HIV and HSV-2
among young women in rural South Africa enrolled in HPTN 068.
AB - OBJECTIVE: To estimate the association between school attendance, school dropout,
and risk of incident HIV and herpes simplex virus type 2 (HSV-2) infection among
young women. DESIGN: We used longitudinal data from a randomized controlled trial
in rural Mpumalanga province, South Africa, to assess the association between
school days attended, school dropout, and incident HIV and HSV-2 in young women
aged 13-23 years. METHODS: We examined inverse probability of exposure weighted
survival curves and used them to calculate 1.5, 2.5, and 3.5-year risk
differences and risk ratios for the effect of school attendance on incident HIV
and HSV-2. A marginal structural Cox model was used to estimate hazard ratios for
the effect of school attendance and school dropout on incident infection.
RESULTS: Risk of infection increased over time as young women aged, and was
higher in young women with low school attendance (<80% school days) compared with
high (>=80% school days). Young women with low attendance were more likely to
acquire HIV [hazard ratio (HR): 2.97; 95% confidence interval (CI): 1.62, 5.45]
and HSV-2 (HR: 2.47; 95% CI: 1.46, 4.17) over the follow-up period than young
women with high attendance. Similarly, young women who dropped out of school had
a higher weighted hazard of both HIV (HR 3.25 95% CI: 1.67, 6.32) and HSV-2 (HR
2.70; 95% CI 1.59, 4.59). CONCLUSION: Young women who attend more school days and
stay in school have a lower risk of incident HIV and HSV-2 infection.
Interventions to increase frequency of school attendance and prevent dropout
should be promoted to reduce risk of infection.
PMID- 28692545
TI - Selection of women at risk for cervical cancer in an HIV-infected South African
population.
AB - OBJECTIVE: Cervical cancer is the leading cause of cancer-related death in women
in South Africa. This study evaluates DNA methylation levels in cervical
(pre)cancer and aims to assess the value of high-risk human papillomavirus
(hrHPV) testing and methylation analysis, alone or in combination, on physician
taken cervical scrapes to detect cervical cancer, and cervical intraepithelial
neoplasia grade 3 (CIN3) in an HIV-infected South African population. DESIGN:
Prospective observational multicentre cohort study. METHODS: Women from a cohort
of women living with HIV (n = 355) and a referral cohort (n = 109, 60% HIV
seropositive) were included. Cervical scrapes were collected for hrHPV testing
and methylation analysis of cell adhesion molecule 1, T-lymphocyte maturation
associated protein, and microRNA124-2 genes. Histologic endpoints were available
for all participants. Performance for detection of CIN3 or worse (CIN3+) was
determined in the cohort of women living with HIV and different testing
strategies were compared. RESULTS: HrHPV and methylation positivity rates
increased with severity of cervical disease in the two study cohorts, each
reaching 100% in samples of women with carcinoma. HrHPV testing showed a
sensitivity for CIN3+ of 83.6%, at a specificity of 67.7%. Methylation analysis
showed a comparable CIN3+ sensitivity of 85.2%, but a significantly lower
specificity of 49.6%. HrHPV testing with reflex methylation analysis showed a
CIN3+ sensitivity of 73.8%, at a specificity of 81.5%. CONCLUSION: In this HIV
infected South African population, stratifying hrHPV-positive women with reflex
methylation analysis detects all cervical carcinomas and yields an acceptable
sensitivity and specificity for CIN3+.
PMID- 28692546
TI - HHV8 and Kaposi's sarcoma: should we really give up protease inhibitors in all
HIV-infected patients?
AB - : We describe the first case of a patient presenting Kaposi's sarcoma with human
herpes virus 8 (HHV8) viremia after switching from a protease inhibitor to an
integrase inhibitor-based combination antiretroviral therapy, followed by a rapid
remission when resuming protease inhibitor. We suggest that the recent
recommendations to switch all HIV patients to protease inhibitor-free regimens
should be carefully re-evaluated especially in MSM HIV patients which are at
higher risks of HHV8 infections and associated malignancies.
PMID- 28692547
TI - Seroprevalence of hepatitis E virus in HIV-infected patients in China.
AB - : The seroprevalence of hepatitis E virus (HEV) in HIV-infected patients in China
has never been reported. Thus, anti-HEV in HIV-infected patients recruited in
five provinces in China was tested. The seroprevalence of HEV was 39.7%, which
was higher than that in the general population (23.5%). HEV infection might be a
frequent cause of hepatitis in HIV-infected patients.
PMID- 28692548
TI - Comparison of vernakalant and ranolazine in atrial fibrillation.
AB - BACKGROUND: Current guidelines recommend vernakalant for pharmacologic
cardioversion of recent-onset atrial fibrillation. However, this drug is not
established as chronic therapy. METHODS AND RESULTS: In total, 15 rabbit hearts
were Langendorff-perfused. A burst pacing protocol-induced atrial fibrillation in
7 of 15 hearts at baseline (10 episodes). Subsequently, a combination of
acetylcholine and isoproterenol (ACH/ISO) has been administered to increase
occurrence of atrial fibrillation resulting in a reduction of atrial action
potential duration (-25 ms, P < 0.05) as well as atrial effective refractory
period (aERP; -36 ms, P < 0.05). Then, atrial fibrillation occurred in all 15
hearts (124 episodes). Additional treatment with vernakalant (10 MUmol/l) induced
a significant reduction of atrial fibrillation (6 of 15 hearts, 63 episodes).
Infusion of vernakalant did not significantly alter atrial action potential
duration (+8 ms) but increased aERP (+16 ms, P < 0.05 as compared with
ACH/ISO).Results were compared to 12 further rabbit hearts treated with
ranolazine. Late sodium current inhibition by ranolazine also induced a
significant increase of aERP. Here, atrial fibrillation was inducible after
ranolazine infusion in 6 of 12 hearts (46 episodes). Of note, 10 of 12 hearts
presented atrial fibrillation during sole treatment with ACH/ISO (174 episodes).
CONCLUSION: Vernakalant and ranolazine demonstrated a comparable antiarrhythmic
efficacy. Therefore, vernakalant treatment may represent a potential therapeutic
option to reduce atrial fibrillation recurrence.
PMID- 28692549
TI - A Case of Familial Hemophagocytic Lymphohistiocytosis Type 4 With Involvement of
the Central Nervous System Complicated With Infarct.
AB - BACKGROUND: Familial hemophagocytic lymphohistiocytosis (HLH) is a fatal disease
affecting infants and very young children. Central nervous system involvement of
HLH can cause catastrophic results. METHOD: We present a case with cranial
involvement of familial HLH type 4 who showed diffuse infiltration of white
matter complicated with intracranial thrombosis. A 5-year-old girl from a
consanguineous couple presented with fever and pancytopenia, and was referred to
our hematology unit. Examination revealed fever, lymphadenopathy, and
hepatosplenomegaly. Ultrasound examination revealed hepatosplenomegaly and free
intra-abdominal fluid. HLH was revealed on bone marrow aspiration biopsy.
Defective natural killer and T lymphocyte cytotoxicity using degranulation tests
was determined. In the genetic analysis, syntaxin gene mutation was found. On T2
weighted and T2-fluid-attenuated inversion recovery magnetic resonance imaging
(MRI), diffuse hyperintense signal changes of cerebral white matter, indicating
white matter demyelination, were observed. A second brain MRI showed an acute
infarct involving the left temporooccipital region. Immunosuppressive therapy
according to the HLH 2004 protocol was started. The infarct resolved but white
matter lesions were stable on the brain MRI that was performed 1 month later.
Brain MRI taken 4 months after the first examination showed stable cerebral white
matter lesions, but hyperintense signal changes appeared in the cerebellar white
matter and were regarded as progression. The patient died because of infection
despite immunosuppressive therapy. CONCLUSIONS: Physicians managing patients with
HLH must be vigilant about the possibility of central nervous system involvement
including stroke.
PMID- 28692551
TI - Can Exchange Transfusion Normalize Serum Levels of Copper, Zinc, and Magnesium in
Severe Neonatal Hyperbilirubinemia?
AB - BACKGROUND: Neonatal hyperbilirubinemia is a frequently encountered problem.
Erythrocytes, especially reticulocytes are rich in copper (Cu) and magnesium (Mg)
so its serum levels increase after hemolysis. Zinc (Zn) plays an important role
in synthesis of some enzymes included in the bilirubin metabolism and may cause
hemolysis. Exchange transfusion is the main treatment for severe neonatal
hyperbilirubinemia but can exchange transfusion affect the previous trace
elements. MATERIALS AND METHODS: We measured Cu, Zn, and Mg serum levels in full
term neonates admitted to neonatal intensive care unit of Minia University
hospital with severe indirect hyperbilirubinemia before and after exchange
transfusion. RESULTS: There were significant higher serum Cu and Mg and lower Zn
serum levels in neonates with hyperbilirubinemia than controls and their levels
were significantly normalized after exchange transfusion. Significant positive
correlations between the total bilirubin levels and hemoglobin, Cu and Mg serum
levels and significant negative correlations with Zn levels were present. There
were no significant correlations between maternal and neonatal serum levels of
any of them. CONCLUSIONS: Exchange transfusion can normalize the significant
higher Cu and Mg and lower Zn serum levels in neonates with severe indirect
hyperbilirubinemia which were not related to their maternal serum levels.
PMID- 28692550
TI - Long-term Pulmonary Outcomes in Pediatric Survivors of High-risk Neuroblastoma.
AB - BACKGROUND: Children with high-risk neuroblastoma are exposed to multimodality
therapies early in life and survivors confront late therapy-related toxicities.
This study assessed respiratory symptoms, pulmonary function tests (PFTs), and
risk factors for abnormalities among survivors. MATERIALS AND METHODS: High-risk
neuroblastoma survivors followed in the long-term follow-up clinic at Memorial
Sloan Kettering Cancer Center were enrolled. Self-administered symptom
questionnaires were completed. Medical records were reviewed for treatment
information and comorbidities. PFTs included spirometry, plethysmography, and
diffusion capacity of the lung for carbon monoxide (DLCO). RESULTS: Thirty-nine
survivors participated (median age at study: 11.4 y; median age at diagnosis: 2.3
y; median time since completion of therapy: 5.5 y). Chronic respiratory symptoms
were reported for 33%. PFT abnormalities were identified in 79% and included low
forced expiratory volume in 1 second (38%), decreased total lung capacity (44%),
and abnormal DLCO (67%). PFT abnormalities were mostly mild to moderate. Mean
forced vital capacity, forced expiratory volume in 1 second, and total lung
capacity were normal and mean DLCO was mildly abnormal. Risks included thoracic
surgery, chest radiation therapy, thoracic surgery plus chest radiation therapy,
and shorter time since completion of therapy (P<0.05). CONCLUSIONS: Although
respiratory abnormalities were common, they were mostly mild or moderate.
Continued pulmonary surveillance of this at-risk population is warranted.
PMID- 28692552
TI - Patient With Niemann-Pick Type C Presenting With a Jaw Mass Characterized With
Lymph Node Involvement by Niemann-Pick Cells.
AB - Niemann-Pick type C disease (NPC) is an autosomal recessive disorder resulting in
accumulation of unesterified lysosomal cholesterol. An 8-year-old girl with NPC
disease had a painless, rigid, and fixed mass measuring 3 cm in diameter located
on the left angular region of mandibula. The mass biopsy showed lipid-laden
phagocytic cells infiltrating the lymph node consistent with Niemann-Pick cells.
In NPC, accumulation of cholesterol in tissues could be seen not only in
reticuloendothelial and nervous systems, but also in all systems. Our case is
important for it being the first case of NPC with submandibular lymphadenopathy
characterized with NPC cell infiltration.
PMID- 28692553
TI - Simultaneous Presentation of Wilms Tumor and Immature Ovarian Teratoma in
Beckwith-Wiedemann Syndrome.
AB - The Beckwith-Wiedemann syndrome is a cancer predisposition syndrome characterized
by a predilection to embryonal tumor growth, especially Wilms tumor,
adrenocortical carcinomas, and hepatoblastomas. Genetic analysis of patients has
revealed a link to the imprinted domain of the 11p15.5 chromosome and methylation
status of the H19 locus and Igf-2. These genes have also been studied in other
cancers, including ovarian teratomas. Our case is a patient with a simultaneous
presentation of a Wilms tumor and immature ovarian teratoma and subsequently
diagnosed with Beckwith-Wiedemann syndrome, which has not been previously
described.
PMID- 28692554
TI - "Minimally Invasive Versus Open Pancreaticoduodenectomy for Cancer. Practice
Patterns and Short-term Outcomes Among 7061 Patients".
PMID- 28692555
TI - Response to the Letter to the Editor: Minimally Invasive Versus Open
Pancreaticoduodenectomy for Cancer Is Associated With Increased 30-day Mortality.
PMID- 28692556
TI - Escalation of Care in Surgery: a Systematic Risk Assessment to Prevent Avoidable
Harm in Hospitalized Patients.
PMID- 28692557
TI - Response to "RE: Escalation of Care in Surgery: A Systematic Risk Assessment to
Prevent Avoidable Harm in Hospitalized Patients".
PMID- 28692558
TI - Robotic Nipple-sparing Mastectomy and Immediate Breast Reconstruction With
Implant: First Report of Surgical Technique.
PMID- 28692559
TI - Comparison of Surgical Resection and Radiofrequency Ablation for Hepatocellular
Carcinoma: Take Care Not to Neglect Radiofrequency Technic and Device.
PMID- 28692560
TI - Treating Very Early-stage HCC: Have We Found the Holy Grail?
PMID- 28692561
TI - Does Participation in the ACS-NSQIP Improve Outcomes?
PMID- 28692562
TI - Response to "Does Participation in the ACS-NSQIP Improve Outcomes?"
PMID- 28692563
TI - Proposals for Shortening UK Surgical Training Will Directly Impact on Patient
Safety.
PMID- 28692564
TI - Is Trainee Participation Really Associated With Adverse Outcomes in Emergency
General Surgery?
PMID- 28692565
TI - An Addition to the Technical Skills Assessment Toolbox.
PMID- 28692567
TI - Auditory Cognitive Training for Pediatric Cochlear Implant Recipients.
AB - OBJECTIVES: Understanding speech in noise is the biggest challenge faced by
individuals with cochlear implants (CIs). Improving speech-in-noise perception
for pediatric CI recipients continues to remain a high priority for all
stakeholders. This study was designed to investigate the efficacy of working
memory training for improving speech-in-noise recognition for children with CIs.
DESIGN: Fourteen children with CIs (aged 6 to 15 years) received adaptive, home
based training on forward digit span task for 5 weeks, while 13 children with CIs
participated in backward digit span training. Seventeen age-matched children with
CIs in the control group received a placebo. Outcome measures included forward
and backward digit span and speech recognition threshold for digit triplets in
noise at pretraining, post-training, and 5-week follow-up. Performance measures
from 26 age-matched children with normal hearing were also obtained only at the
baseline session to generate normative standards for comparison. RESULTS: Digit
span scores were significantly higher at post-training and follow-up compared
with pretraining for both forward- and backward-trained groups. Both trained
groups showed similar training-induced shifts. The control group showed no such
improvement. There was no effect of training on the speech recognition threshold.
Children with CIs showed significantly lower digit span scores and a higher
speech recognition threshold relative to children with normal hearing.
CONCLUSIONS: Training improves working memory capacity as measured by digit spans
for children with CIs. Training-induced improvements are stable for at least 5
weeks. Learning effects demonstrate near-transfer, from forward to backward digit
span and vice versa, but failed to show far-transfer to speech-in-noise
recognition. Current evidence is not supportive of cognitive training for
improving speech-in-noise performance for children with CIs.
PMID- 28692568
TI - Superior Segment Facet Joint Violation During Instrumented Lumbar Fusion is
Associated With Higher Reoperation Rates and Diminished Improvement in Quality of
Life.
AB - STUDY DESIGN: A retrospective cohort study at a single tertiary care center.
OBJECTIVE: To determine the impact of superior segment facet joint violation
(FJV) during lumbar fusion on reoperation rates and quality of life (QOL).
SUMMARY OF BACKGROUND DATA: Although lumbar fusion is an efficacious and durable
treatment for numerous spinal pathologies, adjacent segment degeneration remains
a serious complication. FJV has been suggested to alter load-bearing capability
and potentially contribute to adjacent segment degeneration. MATERIALS AND
METHODS: Patients who underwent instrumented lumbar fusion surgery between 2009
and 2013 with postoperative computed tomography imaging were included. Patients
were placed in the FJV group if either of the superior segment facet joints were
compromised by the pedicle screw or rod. Patients with preserved facet joints
were placed in the control group. Demographic, perioperative, QOL, and
reoperation data were collected. QOL scores including the Pain Disability
Questionnaire, Patient Health Questionnaire-9, and EuroQOL 5 Dimensions (EQ-5D)
were acquired. RESULTS: Of 240 patients included, 112 patients were found to have
FJV and the remaining 128 patients were placed in the control group. One year
following lumbar fusion, QOL outcomes and reoperation rates were similar between
the FJV and control groups. At 2-year follow-up, patients in the FJV group were
less likely to make a significant improvement in EQ-5D (P=0.041). Also, the
reoperation rate in the FJV group was significantly higher than in the control
group at 2 years (15.2% vs. 6.3%, respectively; P=0.024) and 3 years (19.6% vs.
9.4%, P=0.023). Multivariable logistic regression showed FJV to be an independent
predictor of both (1) failing to make a significant improvement in EQ-5D
(P=0.046) and (2) undergoing reoperation at both 2 and 3 years postoperatively
(P=0.024 and 0.020, respectively). CONCLUSIONS: FJV was independently associated
with a higher reoperation rate and diminished improvement in QOL.
PMID- 28692569
TI - Efficacy of Conical Laminoplasty After Thoracic Laminectomy.
AB - STUDY DESIGN: Retrospective clinical study. OBJECTIVE: To evaluate the results of
a new method of laminoplasty, referred to as conical laminoplasty. SUMMARY OF
BACKGROUND DATA: In surgery for a thoracic intradural tumor, laminectomy is
frequently used for tumor resection. However, laminoplasty may be more effective
due to prevention of damage to the posterior elements. This method can be
performed as recapping T-saw laminoplasty and conical laminoplasty which we
refer. MATERIALS AND METHODS: After en bloc laminectomy, conical laminoplasty
(group C; 21 cases) or recapping T-saw laminoplasty (group R; 17 cases) was
performed for patients with thoracic spinal cord tumors. If neither was possible,
laminectomy (group L; 16 cases) was performed. RESULT: The number of laminae
removed and Japanese Orthopedic Association recovery rates did not differ
significantly among the 3 groups. Sagittal kyphosis significantly worsened at
final follow-up in group L, but did not change significantly in groups C and R.
CONCLUSIONS: Conical laminoplasty is particularly useful in a case in which T-saw
laminoplasty cannot be performed due to tumor expansion in the canal and
ossification of the ligamentum flavum. Conical laminoplasty also preserves the
posterior elements, which reduces the risk of worsening of kyphosis
postoperatively.
PMID- 28692570
TI - Payor Reform Opportunities for Spine Surgery: Part II: The Potential Emergence of
Population Health.
AB - The pressures on spine surgery to adopt value-based reimbursement models are
being seen in the increased implementation of bundled payment strategies. Given
that bundled payment models typically link payments to the initiation of the
surgical episode in question, despite their potential cost-saving attributes,
financial incentives remain tied to the volume of services being provided. As
payors and policy makers look to find savings by focusing on waste and variation
of care, more comprehensive models such population health strategies are now
being develop and deployed. The clinical delivery and cost variation currently
seen in spine health management make spine surgery an acute target of such
population health strategies. Spine surgeons should understand the forces driving
such changes and the opportunities to optimize performance within them.
PMID- 28692571
TI - Efficacy of Target Drug Delivery and Dead Space Reduction Using Antibiotic-loaded
Bone Cement for the Treatment of Complex Spinal Infection.
AB - STUDY DESIGN: A retrospective study. OBJECTIVES: We have treated complex cases of
surgical site infection (SSI) successfully using antibiotic-loaded bone cement to
avoid the need for implant removal. In the present study, we describe a new
treatment option for SSI. SUMMARY OF BACKGROUND DATA: Although there are several
treatment options for SSI after spinal surgery involving instrumentation, several
types of problems may arise and are difficult to cure. MATERIALS AND METHODS:
Eleven patients with SSI after undergoing spinal surgery involving
instrumentation were studied. All had been refractory to conventional treatments,
including intravenous antibiotic administration and conventional debridement and
irrigation. Antibiotic-loaded bone cement was placed on and around the
instrumentation to cover them and to occupy the surrounding dead space. Two
general types of antibiotics were loaded into the polymethylmethacrylate bone
cement. The recipes for the mixture were changed depending on the bacterial
cultures. Sensitive antibiotics were administered generally for 2-6 weeks until
the C-reactive protein level was normalized. RESULTS: All patients were treated
successfully using antibiotic-loaded bone cement. Only 1 patient needed a repeat
of this procedure to treat an infection. Antibiotic-loaded bone cement was placed
in situ in all patients during the follow-up period and there were no significant
adverse events. CONCLUSIONS: Antibiotic-loaded bone cement treatment reduces the
dead space and achieves the targeted drug delivery simultaneously. Treatment
using antibiotic-loaded bone cement is an effective treatment option for complex
spinal SSI.
PMID- 28692572
TI - Health Care Engagement and Follow-up After Perceived Discrimination in Maternity
Care.
AB - BACKGROUND: Negative experiences in the health care system, including perceived
discrimination, can result in patient disengagement from health care. Four
million US women give birth each year, and the perinatal period is a time of
sustained interaction with the health care system, but potential consequences of
negative experiences have not been examined in this context. We assessed whether
perceived discrimination during the birth hospitalization were associated with
postpartum follow-up care. METHODS: Data were from the Listening to Mothers III
survey, a nationally drawn sample of 2400 women with singleton births in US
hospitals in 2011-2012. We used multivariate logistic regression to estimate
adjusted odds of having a postpartum visit in the 8 weeks following birth by
perceptions of discrimination due to (1) race/ethnicity; (2) insurance type; and
(3) a difference of opinion with a provider about care. RESULTS: Women who
experienced any of the 3 types of perceived discrimination had more than twice
the odds of postpartum visit nonattendance (adjusted odds ratio=2.28, P=0.001),
after adjusting for socioeconomic and medical characteristics. CONCLUSIONS: The
postpartum visit is an opportunity for a patient and clinician to address
continuing health problems following birth, discuss contraception, and screen for
chronic disease. Forgoing this care may have negative health effects. The
findings from this study underscore the need to reduce discrimination and improve
maternity care experiences.
PMID- 28692573
TI - Associations of Hospice Disenrollment and Hospitalization With Continuous Home
Care Provision.
AB - OBJECTIVES: To examine rates of hospice disenrollment and posthospice
hospitalization among patients who are enrolled in hospices that provide
continuous home care (CHC) (CHC hospices) compared with patients who are enrolled
in hospices that do not offer CHC (non-CHC hospices). METHODS: We performed a
retrospective cohort study among Medicare fee-for-service decedents between July
and December 2011, who were 66 years and older and had used hospice in their last
6 months of life. We used propensity score matching to account for potential
confounding characteristics of hospices. Generalized estimating equation models
were applied to estimate between CHC hospices and non-CHC hospices the
associations of hospice disenrollment/hospitalization, adjusted for patient
characteristics. We also conducted subgroup analyses to examine how the
association might have differed by hospice size, and by the percentage of
enrollees who received CHC. RESULTS: After matching, we identified 936 pairs of
CHC and non-CHC hospices, well balanced in terms of organizational
characteristics. In fully adjusted models, compared with non-CHC hospices, CHC
hospices had significantly lower disenrollment rates (adjusted rate ratio, 0.73;
95% confidence interval, 0.60-0.87), and lower hospitalization rates (adjusted
rate ratio, 0.79; 95% confidence interval, 0.66-0.95). These associations were
significantly more pronounced among larger hospices (those with >175 enrollees
during study period), and among hospices in which at least 7.3% of enrollees used
CHC. CONCLUSIONS: CHC hospices had significantly lower rates of hospice
disenrollment and posthospice hospitalization, suggesting CHC service available
may enable higher quality of end-of-life care.
PMID- 28692574
TI - Technician Consistency in Specular Microscopy Measurements: A "Real-World"
Retrospective Analysis of a United States Eye Bank.
AB - PURPOSE: To quantify consistency of endothelial cell density (ECD) measurements
among technicians in a single US eye bank operating under typical operating
conditions. METHODS: In this retrospective analysis of 51 microscopy technicians
using a semiautomated counting method on 35,067 eyes from July 2007 to May 2015,
technician- and date-related marginal ECD effects were calculated using linear
regression models. ECD variance was correlated with the number of specular
microscopy technicians. RESULTS: Technician mean ECDs ranged from 2386 +/- 431 to
3005 +/- 560 cells/mm. Nine technicians had statistically and clinically
significant marginal effects. Annual mean ECDs adjusted for changes in
technicians ranged from 2422 +/- 433 to 2644 +/- 430 cells/mm. The period of 2007
to 2009 had statistically and clinically significant marginal effects. There was
a nonstatistically significant association between the number of technicians and
ECD standard deviation. CONCLUSIONS: There was significant ECD variability
associated with specular microscopy technicians and with the date of measurement.
We recommend that eye banks collect data related to laboratory factors that have
been shown to influence ECD variability.
PMID- 28692577
TI - Associations Between Feeding Problems and Maternal Sensitivity Across Infancy:
Differences in Very Preterm and Full-Term Infants.
AB - OBJECTIVE: To determine the influence of maternal sensitivity on infant feeding
problems in very preterm/very low birth weight (VP/VLBW) and full-term (FT)
infants. METHODS: Longitudinal study of 178 infants (73 VP/VLBW and 105 FT).
Feeding problems and maternal sensitivity were assessed at term, 3 and 18 months.
A cross-lagged path model was tested to assess the longitudinal associations.
RESULTS: The direction of the association between maternal sensitivity and
feeding problems differed among VP/VLBW and FT infants. In VP/VLBW infants,
higher feeding problems at term and 3 months were associated with less maternal
sensitivity at 3 months (beta = -.27, p < .05) and at 18 months (beta = -.36, p <
.05), respectively. In FT infants, a reciprocal relationship of feeding problems
and maternal sensitivity over time was found. Feeding problems at 3 months were
associated with decreased maternal sensitivity at 18 months (beta = -.32, p <
.05), whereas decreased maternal sensitivity at 3 months was related to increased
feeding problems at 18 months (beta = -.25, p < .05). CONCLUSION: Feeding
problems are frequent in VP/VLBW infants and subsequently are associated with
poorer maternal sensitivity. In FT infants, poorer levels of maternal sensitivity
were both predicted by feeding problems but also were associated with more
feeding problems over time.
PMID- 28692575
TI - Rendering factor Xa zymogen-like as a therapeutic strategy to treat bleeding.
AB - PURPOSE OF REVIEW: New therapies are needed to control bleeding in a range of
clinical conditions. This review will discuss the biochemical properties of
zymogen-like factor Xa, its preclinical assessment in different model systems,
and future development prospects. RECENT FINDINGS: Underlying many procoagulant
therapeutic approaches is the rapid generation of thrombin to promote robust clot
formation. Clinically tested prohemostatic agents (e.g., factor VIIa) can provide
effective hemostasis to mitigate bleeding in hemophilia and other clinical
situations. Over the past decade, we explored the possibility of using zymogen
like factor Xa variants to rapidly improve clot formation for the treatment of
bleeding conditions. Compared to the wild-type enzyme, these variants adopt an
altered, low activity, conformation which enables them to resist plasma protease
inhibitors. However, zymogen-like factor Xa variants are conformationally dynamic
and ligands such as its cofactor, factor Va, stabilize the molecule rescuing
procoagulant activity. At the site of vascular injury, the variants in the
presence of factor Va serve as effective prohemostatic agents. Preclinical data
support their use to stop bleeding in a variety of clinical settings. Phase 1
studies suggest that zymogen-like factor Xa is safe and well tolerated, and a
phase 1b is ongoing to assess safety in patients with intracerebral hemorrhage.
SUMMARY: Zymogen-like factor Xa is a unique prohemostatic agent for the treatment
of a range of bleeding conditions.
PMID- 28692578
TI - Turning 1 Year of Age in a Low Socioeconomic Environment: A Portrait of
Disadvantage.
AB - : In the United States today, 16 million children are growing up poor. Few
studies report multiple environmental factors associated with poverty during the
first year of life and effects on infant development. OBJECTIVES: To evaluate
maternal, home, and neighborhood environment of low and higher socioeconomic
status (SES) infants from birth to 1 year and to evaluate the impact of SES and
environment on infant developmental outcome at 1 year. METHODS: Low (n = 30) and
higher SES (n = 30) African-American mothers and their healthy term gestation
female infants were prospectively compared for environmental characteristics and
infant developmental outcome. Wechsler Adult Intelligence Scale-IV (WAIS-IV);
Beck Depression Inventory; Perceived Stress Scale; Parenting Stress Index-Fourth
Edition (PSI-4); Social Support Scale; Home Observation Measurement of the
Environment (HOME); Household Food Insecurity (HFI); Concentrated Neighborhood
Disadvantage (CND). Bayley Scales of Infant Development Third Edition (BSID-III);
Preschool Language Scale (PLS-5). RESULTS: Environmental risk was greater for low
compared with higher SES: lower WAIS-IV (p < .001); higher PSI-4 total (p =
.003); lower HOME total and 3 subscales (p < .002); higher HFI (p = .012); and
higher CND (p = .027). Low SES infant outcomes differed from higher SES: lower
BSID-III Cognitive Composite (p = .005), PLS-5 Total Language (p <= .017), and
Auditory Comprehension (p <= .008). In regressions, after controlling for SES,
effects of environmental factors were not found. CONCLUSION: By age 1, low SES
infants had been exposed to greater environmental disadvantage and already
exhibited poorer developmental functioning than higher SES infants. These
findings suggest that support for families and children from impoverished
circumstances cannot begin too early.
PMID- 28692580
TI - HIV Infection Increases the Risk of Incident Psoriasis: A Nationwide Population
Based Cohort Study in Taiwan.
AB - BACKGROUND: HIV can cause an imbalance of T lymphocytes, which may contribute to
the onset of psoriasis. However, the association of HIV with incident psoriasis
has not been extensively studied. OBJECTIVES: The aim of this nationwide
population-based cohort study was to determine the association of HIV with
incident psoriasis. METHODS: Since January 1, 2000, we identified adult people
living with HIV/AIDS (PLWHA) from the Taiwan National Health Insurance Research
Database. A control cohort without HIV infection, matched for age and sex, was
selected for comparison. All patients were followed until December 31, 2012, and
observed for the occurrence of psoriasis. The time-dependent Cox proportional
hazards model was used to determine the association of HIV with incident
psoriasis, while considering death as a competing risk event. RESULTS: Of the
102,070 patients (20,294 PLWHA and 81,776 matched controls), 248 (0.24%) had
incident psoriasis during a mean follow-up period of 5.53 years, including 81
(0.40%) PLWHA and 171 (0.21%) controls. After adjusting for age, sex, and
comorbidities, HIV infection was found to be an independent risk factor for
incident psoriasis (adjusted hazard ratio, 1.80; 95% confidence interval: 1.38 to
2.36). CONCLUSIONS: The population of PLWHA is living longer; clinicians need to
be aware of their higher risk of psoriasis.
PMID- 28692581
TI - Delta9-Tetrahydrocannabinol Suppresses Secretion of IFNalpha by Plasmacytoid
Dendritic Cells From Healthy and HIV-Infected Individuals.
AB - Plasmacytoid dendritic cells (pDCs) play a crucial role in host antiviral immune
response through secretion of type I interferon. Interferon alpha (IFNalpha), a
type I IFN, is critical for mounting the initial response to viral pathogens. A
consequence of Human Immunodeficiency Virus-1 (HIV) infection is a decrease in
both pDC number and function, but prolonged pDC activity has been linked with
progression from HIV infection to the development of AIDS. Patients with HIV in
the United States routinely use cannabinoid-based therapies to combat the side
effects of HIV infection and antiretroviral therapy. However, cannabinoids,
including Delta-tetrahydrocannabinol (THC), are well-characterized
immunosuppressants. Here, we report that THC suppressed secretion of IFNalpha by
pDC from both healthy and HIV+ donors through a mechanism involving impaired
phosphorylation of interferon regulatory factor 7. These results suggest that THC
can suppress pDC function during the early host antiviral response by dampening
pDC activation.
PMID- 28692582
TI - Iatrogenic Hip Instability Treated With Periacetabular Osteotomy.
AB - Hip dislocation following hip arthroscopy is a devastating complication. Previous
reports of arthroscopy-related iatrogenic instability have focused on strategies
aimed at restoring the stabilizing effects of the hip joint capsuloligamentous
complex. Less has been written about treatment options for patients in whom
deficient acetabular coverage of the femoral head is implicated in the
functionally unstable hip joint. Given this relative paucity of information, an
optimal treatment approach has yet to be elucidated for these patients.
Periacetabular osteotomy has been described as a treatment for iatrogenic hip
instability related to surgical hip dislocation; however, to our knowledge, this
is the first case of a patient with hip arthroscopy-related iatrogenic
instability manifesting as recurrent, frank dislocations treated with
periacetabular osteotomy.
PMID- 28692583
TI - Management of Spinal Conditions in Patients With Parkinson Disease.
AB - Parkinson disease (PD) is increasingly prevalent in the aging population. Spine
disorders in patients with PD may be degenerative in nature or may arise
secondary to motor effects related to the parkinsonian disease process.
Physicians providing care for patients with PD and spine pathologies must be
aware of several factors that affect treatment, including the patterns of spinal
deformity, complex drug interactions, and PD-associated osteoporosis. Following
spine surgery, complication rates are higher in patients with PD than in those
without the disease. Literature on spine surgery in this patient population is
limited by small cohort size, the heterogeneous patient population, and variable
treatment protocols. However, most studies emphasize the need for preoperative
optimization of motor control with appropriate medications and deep brain
stimulation, as well as consultation with a movement disorder specialist. Future
studies must control for confounding variables, such as the type of surgery and
PD severity, to improve understanding of spinal pathology and treatment options
in this patient population.
PMID- 28692584
TI - Association between risk factors and detection of cutaneous melanoma in the
setting of a population-based skin cancer screening.
AB - Early detection is considered to improve the prognosis of cutaneous melanoma. The
value of population-based screening for melanoma, however, is still
controversial. The aim of this study was to evaluate the predictive power of
established risk factors in the setting of a population-based screening and to
provide empirical evidence for potential risk stratifications. We reanalyzed data
(including age, sex, risk factors, and screening results) of 354 635 participants
in the Skin Cancer Research to provide Evidence for Effectiveness of Screening in
Northern Germany (SCREEN)project conducted in the German state of Schleswig
Holstein (2003-2004). In multivariable analysis, atypical nevi [odds ratio (OR):
17.4; 95% confidence interval (CI): 14.4-20.1], personal history of melanoma (OR:
5.3; 95% CI: 3.6-7.6), and multiple (>=40) common nevi (OR: 1.3; 95% CI: 1.1-1.6)
were associated with an increased risk of melanoma detection. Family history and
congenital nevi were not significantly associated with melanoma detection in the
SCREEN. The effects of several risk-adapted screening strategies were evaluated.
Hypothesizing a screening of individuals aged more than or equal to 35 years,
irrespective of risk factors (age approach), the number needed to screen is 559
(95% CI: 514-612), whereas a screening of adults (aged >=20) with at least one
risk factor (risk approach) leads to a number needed to screen of 178 (95% CI:
163-196). Converted into one screen-detected melanoma, the number of missed
melanomas is 0.15 (95% CI: 0.12-0.18) with the age approach and 0.22 (95% CI:
0.19-0.26) with the risk approach. The results indicate that focusing on
individuals at high risk for melanoma may improve the cost-effectiveness and the
benefit-to-harm balance of melanoma screening programs.
PMID- 28692585
TI - Association between alcohol consumption and colorectal cancer risk: a case
control study in the Han Chinese population.
AB - Many epidemiologic studies have reported that alcohol is a risk factor for
colorectal cancer. To further evaluate the association, we carried out a case
control study in the Han Chinese population. From February 2008 to February 2013,
we carried out a hospital-based case-control study on colorectal cancer.
Information was collected using a questionnaire. Cases were 310 patients with
colorectal cancer; 620 healthy matched controls were also recruited. Multiple
logistic regression was used to estimate the odds ratios (OR) and the
corresponding 95% confidence intervals. Alcohol consumption was associated with
increased colorectal cancer risk, but OR was significant only among heavy
drinkers (OR=2.18, for >=21 drinks/week). Colorectal cancer risk was 4.01-fold
higher in heavy smokers (>=20 cigarettes/day) and heavy drinkers (>=21
drinks/week) in comparison with never smokers who consumed less than 7
drinks/week. The relationship was strengthened by stratified studies of sex.
Among former drinkers, the excess of risk disappeared in those who had quit for
at least 10 years (OR=0.86). Our study confirmed that heavy alcohol consumption
was associated with an increasing risk of colorectal cancer; smoking modified
this relationship, especially heavy smokers. Further data from large cohorts are
desirable for conclusive confirmation.
PMID- 28692586
TI - Bioactivity and prostate tissue distribution of metformin in a preprostatectomy
prostate cancer cohort.
AB - Metformin has recently been shown to have potential to reduce prostate cancer
risk. We conducted a randomized, double-blind, placebo-controlled trial to
determine the modulating effects of metformin on tissue and systemic biomarkers
of drug activity and its distribution into the prostate tissue. Twenty patients
with prostate cancer scheduled to undergo prostatectomy were randomly assigned to
receive either extended-release metformin or placebo for a median of 34 days
before surgery. Prostatectomy and serum samples were analyzed for metformin
concentrations, serum biomarkers of drug activity (prostate-specific antigen,
insulin, insulin-like growth factor-1, insulin-like growth factor binding protein
3, sex hormone-binding globulin, and testosterone) and tissue biomarkers of
proliferation, apoptosis, cell cycle regulation, and mTOR inhibition. For
participants in the metformin arm, the prostate tissue and serum metformin
concentrations ranged from 0.88 to 51.2 MUg/g tissue and from not detectable to
3.6 MUg/ml, respectively. There were no differences between the two groups in
either the postintervention tissue biomarker expression in the prostatectomy
tissue or pre to postintervention changes in serum biomarkers. We conclude that
metformin distributes to human prostate tissue, suggesting that metformin could
exert its effects directly on tissue targets. However, there was no difference in
tissue and systemic drug effect biomarkers between the two treatment arms. Future
studies with longer intervention duration and larger sample size should be
considered in order to evaluate the potential of metformin for prostate cancer
prevention.
PMID- 28692587
TI - Colorectal cancer and markers of anemia.
AB - Unexplained iron-deficiency anemia is an important marker for colorectal cancer
(CRC). Our objectives were as follows: (a) to assess whether the association
between anemia and CRC can be detected on the 'Clinical Practice Research
Datalink', (b) to evaluate the timing between laboratory changes and CRC
detection, and (c) to analyze its association with survival. We conducted a case
control study on patients with an incident CRC diagnosis during 2008-2012 and a 1
: 1-matched control group. We compared anemia markers serum ferritin (SF),
hemoglobin (Hb), mean corpuscular volume (MCV), and red blood cell count between
cases and controls using conditional logistic regression. We assessed survival in
CRC cases. SF values up to 20 ng/ml were associated with an odds ratio [OR (95%
confidence interval)] of 10.66 (6.88-16.51) compared with SF values of 101-300
ng/ml when restricted to measurements up to 180 days before the CRC diagnosis.
For measurements taken at 1 year or earlier before the diagnosis, the OR was 2.02
(1.57-2.61). For Hb values less than 9 g/dl compared with Hb values of 13.0-15.9
g/dl the corresponding ORs were 74.25 (34.69-158.91) and 2.19 (1.31-3.67),
respectively. The corresponding ORs for MCV values up to 80 fl compared with MCV
values of 86-95 fl were 13.94 (10.31-18.85) and 1.89 (1.51-2.36), respectively.
Low levels of these markers were only weakly associated with survival. Hb, MCV,
and SF levels substantially dropped only shortly before the CRC diagnosis.
Although slightly more cases had anemia markers compared with controls at 1 year
or earlier before the diagnosis, most cases still had normal values. The Clinical
Practice Research Datalink is well-suited to detect associations between low Hb,
MCV, and SF levels and CRC.
PMID- 28692588
TI - Utilization of colonoscopy and colonoscopic findings among individuals aged 40-54
years with a positive family history of colorectal cancer: a cross-sectional
study in general practice.
AB - Guidelines recommend early colonoscopy for individuals with a positive family
history of colorectal cancer (CRC), but little is known about the utilization of
colonoscopy and the frequency of colorectal neoplasms among younger affected
individuals in Germany. The aim of this study was to determine the utilization of
colonoscopy and the frequency of colorectal neoplasms in this risk group. We
conducted a cross-sectional study in a general practice setting. Patients aged 40
54 years with at least one first-degree relative with CRC were identified,
counseled on their increased risk, and referred to colonoscopy if they decided to
undergo this procedure. We assessed the reported utilization of colonoscopy
before study participation with a questionnaire and obtained results of
colonoscopies performed during the study period from colonoscopy reports. Out of
484 patients with a positive family history of CRC, 191 (39.5%) fulfilled the
inclusion criteria and participated in the study: 54% reported that at least one
colonoscopy had been performed before study participation. Out of 191
participants, 86 (45%) underwent a colonoscopy during study period. No CRC was
found, but 16.3% had any adenoma, and 7.0% had advanced adenomas. Overall, 155
(82%) study participants underwent a colonoscopy either before or during the
study period. The utilization of colonoscopies among participants was remarkably
high even before study participation. This rate increased up to 82% after
counseling by general practitioners. A relevant number of participants had
(advanced) adenomas. It appears worthwhile to involve general practitioners in
identifying and counseling younger individuals with familial risk for CRC.
PMID- 28692589
TI - Emerging cancer-specific therapeutic aptamers.
AB - PURPOSE OF REVIEW: We will describe recently discovered smart aptamers with tumor
specificity, with an emphasis on targeted delivery of novel therapeutic
molecules, cancer-specific biomarkers, and immunotherapy. RECENT FINDINGS: The
development of cancer-specific aptamers has facilitated targeted delivery of
potent therapeutic molecules to cancer cells without harming nontumoral cells.
This specificity also makes it possible to discover novel cancer biomarkers.
Furthermore, alternative immune-checkpoint blockade aptamers have been developed
for combinational immunotherapy. SUMMARY: Aptamers selected against cancer cells
show cancer specificity, which has great potential for targeting. First,
functionalizing targeted aptamers with therapeutic molecule payloads (e.g., small
activating RNAs, antimitotic drugs, therapeutic antibodies, and peptides)
facilitates successful delivery into cancer cells. This approach greatly improves
the therapeutic index by minimizing side-effects in nontumoral cells. Second,
cancer-specific proteins have been identified as cancer biomarkers through in
vitro and in-vivo selection, aptamer pull-down assays, and mass spectrometry.
These newly discovered biomarkers improve therapeutic intervention and diagnostic
specificity. In addition, the development of alternative immune-checkpoint
blockade aptamers is suggested for use in combinational immunotherapeutic with
current immune blockade regimens, to reduce the resistance and exhaustion of T
cells in clinical trials. VIDEO ABSTRACT: http://links.lww.com/COON/A21.
PMID- 28692590
TI - Vestibular Schwannoma Growth With Aspirin and Other Nonsteroidal Anti
inflammatory Drugs.
AB - OBJECTIVE: To investigate whether the use of aspirin or other non-steroidal anti
inflammatory drugs (NSAIDs) impact the growth of vestibular schwannoma (VS).
STUDY DESIGN: Retrospective case series. SETTING: Single academic, tertiary care
center. PATIENTS: Patients with VS who underwent at least two magnetic resonance
imaging (MRI) studies before intervention. INTERVENTION(S): Serial MRI studies.
MAIN OUTCOME MEASURE(S): VS tumor growth, defined as more than or equal to 2 mm
increase in the maximum tumor diameter between consecutive MRI studies, or
between the first and last available study. Mean growth rate was also calculated,
defined as the change in tumor size divided by length of follow-up. RESULTS: A
total of 564 VS patients met inclusion criteria, with 234 (41.2%) taking some
type of NSAID. Aspirin use was not associated with VS tumor growth, presenting
tumor diameter, or mean VS growth rate. Further, aspirin dosage did not impact
growth outcomes or presenting tumor diameter. A total of 96 (17.0%) patients took
an NSAID other than aspirin. Neither non-aspirin NSAID use nor degree of
cyclooxygenase-2 (COX-2) selectivity, including aspirin, was significantly
associated with VS tumor growth, presenting tumor diameter, or mean VS growth
rate. CONCLUSIONS: While previous studies have suggested a relationship between
aspirin usage and VS growth, we found no significant association in our series of
564 observed VS. Furthermore, there was no apparent relationship between aspirin
dosage, non-aspirin NSAID use, and COX-2 selectivity with VS growth, presenting
tumor diameter at presentation, or mean VS growth rate.
PMID- 28692591
TI - Development and Validation of a Modular Endoscopic Ear Surgery Skills Trainer.
AB - OBJECTIVE: Endoscopic ear surgery (EES) is an emerging technique requiring single
handed dissection with limited depth perception. Current options for EES
simulation and training are limited. Herein, we introduce a versatile, low-cost
surgical skills trainer that aims to improve the fine motor control necessary for
EES. STUDY DESIGN: Prospective validation study. SETTING: Surgical simulation
laboratory. PARTICIPANTS: Seven subjects ranging in experience from medical
students ("Novices") to experienced ear surgeons ("Experts") participated in the
validation study. Experts (n = 3) were defined as performing >10 EES cases per
year. METHODS: The skills trainer was constructed from a 3" diameter polyvinyl
chloride pipe cap modified with two ports for instrument passage. A wooden
platform was placed inside at an appropriate working distance for ear surgery.
Eight interchangeable skills modules were fabricated on wooden squares (3 cm * 3
cm) using materials such as #19 wire brads, 1.6 mm glass beads, and 26-gauge
jewelry wire. The material cost of this reusable model was $15. Subjects
completed each skills module in triplicate, followed by a Likert-based survey.
RESULTS: Expert performance was superior to novices in 100% (8/8) of skills
modules, i.e., threading beads on a wire (43 versus 127 s, p < 0.001) and placing
a simulated prosthesis (13 versus 68 s, p = 0.01). Most participants (86%) agreed
the trainer orientation was accurate and all participants (100%) were satisfied
with the experience. CONCLUSIONS: This low-cost modular task trainer may help
fill a void in otologic training by allowing efficient, deliberate practice of
validated exercises designed to improve fine motor control with EES
instrumentation.
PMID- 28692592
TI - Reduction in Temporary and Permanent Audiological Injury Through Internal Jugular
Vein Compression in a Rodent Blast Injury Model.
AB - HYPOTHESIS: Internal jugular vein (IJV) compression influences not only
intracranial but also intracochlear physiology and has demonstrated preclinical
effectiveness in reducing acute audiological injury in a rodent blast model.
However, the long-term effects in this model are unknown. BACKGROUND: Blast wave
induced audiological injury from an improvised explosive device is a leading
cause of morbidity among service members in theater but there are limitations to
the current protective measures. METHODS: For this study, we exposed 20 Sprague
Dawley rats to a 16.8 +/- 0.3 PSI (195.3 dB SPL) right-sided shock wave in which
10 had application of a custom IJV compression collar in place at the time of
injury. RESULTS: IJV compression at the time of injury was shown acutely to
significantly reduce the incidence of tympanic membrane rupture and the initial
temporary threshold shift on otoacoustic emissions in both the right and left
ears of animals who had collar application immediately after and 7 days post
injury. At 28 days from injury, collared animals demonstrated a return to
baseline of otoacoustic emission values while the noncollared animals had
persistent threshold shifts, signifying the presence of a permanent threshold
shift only in those animals without collar application. IJV compression was also
found to significantly reduce hair cell loss at the base of the cochlea secondary
to mechanical trauma from the blast wind. CONCLUSION: Previously observed acute
protective effects of IJV compression are sustained at chronic time points. IJV
compression can potentially be used to reduce long-term permanent morbidity from
blast-induced audiological trauma.
PMID- 28692593
TI - Carcinoma of the Middle Ear: A Review of the National Cancer Database.
AB - INTRODUCTION: Malignancy of the middle ear is a rare condition with limited data
available for clinical guidance. STUDY DESIGN: Retrospective evaluation of a
large national database. SETTING: Deidentified national cancer database.
PATIENTS: Subjects with diagnosis of malignancy of the middle ear in the National
Cancer Database between 2004 and 2012. MAIN OUTCOME MEASURES: Demographic
information and tumor characteristics were evaluated. The primary endpoint of
interest is overall survival. RESULTS: The most common histology was squamous
cell carcinoma (SCC) (50%). Multivariable Cox proportional hazard analysis found
the following variables had a significant negative impact on overall survival:
age (HR 1.04 95% CI [1.02-1.05]), squamous cell carcinoma, not otherwise
specified (NOS) (HR 2.08 95% CI [1.30-3.32]), squamous cell carcinoma,
keratinizing, NOS (HR 4.20 95% CI [2.14-8.24]), embroynal rhabdomyosarcoma, NOS
(HR 4.96 95% CI [1.17-21.11]), and unknown extension (HR 2.87 95% CI [1.22
6.74]). For patients of SCC who underwent surgery, 30 had positive margins and 29
underwent adjuvant radiation. For these, no survival advantage was found with the
addition of chemotherapy, regardless of node status. CONCLUSION: Malignancy of
the middle ear is a rare condition with prognosis that depends on histology. The
most common histology, SCC, is associated with the poorest overall survival.
Evaluation of large national datasets can add significantly to the understanding
of such uncommon tumors.
PMID- 28692594
TI - Measuring Rates of Visual Field Progression in Linear Versus Nonlinear Scales:
Implications for Understanding the Relationship Between Baseline Damage and
Target Rates of Glaucoma Progression.
AB - PURPOSE: The purpose of this study is to test the hypothesis that the
relationship between baseline visual field damage and the rate of progression
depends upon the use of logarithmic (dB) versus linear (1/Lambert) scale.
METHODS: A total of 60 eyes (60 patients) with treated, established glaucoma and
at least 5 reliable 24-2 visual fields were included. Baseline visual field mean
deviation (MD) in dB was transformed to 1/Lambert using standard equation. Mixed
effects linear regression was used to calculate the slopes (MD rates of
progression over time) with linear and nonlinear scales. We tested the
relationship between baseline MD and MD slopes for each scale of measure.
RESULTS: In dB scale, worse baseline visual field loss was associated with faster
MD slopes (P=0.037), whereas the opposite effect was seen in 1/Lambert (P=0.001).
For a similar rate of progression in dB/y, eyes with mild visual field damage
lost more linear sensitivity over a given period of time than those with more
severe baseline damage. CONCLUSIONS: There is a significant relationship between
baseline visual field severity and rates of MD progression, although the
direction of this association depends on the scale sensitivity is measured. The
definition of fast versus slow visual field progression should be revised and
take into account that sensitivity in linear scales show a better correlation
with structural loss than when conventionally measured in nonlinear scale.
PMID- 28692595
TI - The Quantitative Measurements of Vascular Density and Flow Area of Optic Nerve
Head Using Optical Coherence Tomography Angiography.
AB - PURPOSE: The purpose of this study was to evaluate the vascular density (VD) and
the flow area on optic nerve head (ONH) and peripapillary area, and the impact of
age and sex using optical coherence tomography angiography (OCTA) in healthy
human subjects. METHODS: Both eyes of each volunteer were scanned by an RTVue XR
Avanti; Optovue with OCTA using the split-spectrum amplitude-decorrelation
angiography algorithm technique. Masked graders evaluated enface angiodisc OCTA
data. The flow area of ONH and the VD were automatically calculated. RESULTS: A
total of 79 eyes of patients with a mean age of 37.03+/-11.27 were examined. The
total ONH (papillary and peripapillary) area VD was 56.03%+/-4.55%. The flow area
of the ONH was 1.74+/-0.10 mm/1.34 mm. The temporal and inferotemporal
peripapillary VD was different between male and female patients. Increasing age
causes some changes in the flow area of the ONH and the papillary VD from the
third to the fourth decade (analysis of variance test; P<0.05). CONCLUSIONS: A
normal quantitative database of the flow area and VD of the papillary and
peripapillary area, obtained by RTVue XR with OCT angiography technique, is
presented here.
PMID- 28692596
TI - Inadvertent Cyclodialysis Cleft and Hypotony Following Ab-Interno Trabeculotomy
Using the Trabectome Device Requiring Surgical Repair.
AB - PURPOSE: To report the first case of inadvertent cyclodialysis cleft and hypotony
requiring surgical repair following ab-interno trabeculotomy (AIT) using the
Trabectome device, and the postoperative clinical results following direct suture
cyclopexy. METHODS: A 55-year-old man with hypotonous maculopathy secondary to
cyclodialysis cleft inadvertently created 3 years earlier during AIT using the
Trabectome device was referred for repair. Direct suture cyclopexy was performed
and topical homatropine and dexamethasone drops were prescribed postoperatively.
RESULTS: Gonioscopic examination revealed complete cleft closure on postoperative
day 1 confirmed by anterior segment optical coherence tomography. At 11 weeks
postoperatively, visual acuity had improved from 20/400 to 20/40, with resolution
of preoperative macular folds on fundoscopic examination. At 9 months
postoperatively, visual acuity had further improved to 20/20 with intraocular
pressure stable at 9 mm Hg maintained on travoprost and brimonidine. CONCLUSIONS:
Inadvertent cyclodialysis cleft from a malpositioned AIT and resultant hypotony
is rare and in this case was successfully treated by direct suture cyclopexy.
PMID- 28692597
TI - Practice Preferences for Glaucoma Surgery: A Survey of the American Glaucoma
Society.
AB - PURPOSE: The purpose of this study is to assess surgical practice patterns among
the American Glaucoma Society (AGS) membership. METHODS: An anonymous online
survey evaluating the use of glaucoma surgeries in various clinical settings was
redistributed to AGS members. Survey responses were compared with prior results
from 1996, 2002, and 2008 to determine shifts in surgical practice patterns.
Questions were added to assess the preferred approach to primary incisional
glaucoma surgery and phacoemulsification combined with glaucoma surgery. RESULTS:
A total of 252 of 1091 (23%) subscribers to the AGS-net participated in the
survey. Percentage use (mean+/-SD) of trabeculectomy with mitomycin C (MMC),
glaucoma drainage device (GDD), and minimally invasive glaucoma surgery (MIGS) as
an initial surgery in patients with primary open angle glaucoma was 59%+/-30%,
23%+/-23%, and 14%+/-20%, respectively. Phacoemulsification cataract extraction
alone was the preferred surgical approach in 44%+/-32% of patients with primary
open angle glaucoma and visually significant cataract, and phacoemulsification
cataract extraction was combined with trabeculectomy with MMC in 24%+/-23%, with
MIGS in 22%+/-27%, and with GDD in 9%+/-14%. Although trabeculectomy was selected
most frequently to surgically manage glaucoma in 8 of 8 clinical settings in
1996, GDD was preferred in 7 of 8 clinical settings in 2016. CONCLUSIONS: The use
of GDD has increased and that of trabeculectomy has concurrently decreased over
the past 2 decades. Trabeculectomy with MMC is the most popular primary
incisional surgery when performed alone or in combination with
phacoemulsification cataract extraction. Surgeons frequently manage coexistent
cataract and glaucoma with cataract extraction alone, rather than as a combined
cataract and glaucoma procedure.
PMID- 28692598
TI - Membrane lipids and cell signaling.
AB - PURPOSE OF REVIEW: Reception and transmission of signals across the plasma
membrane has been a function generally attributed to transmembrane proteins. In
the last 3 years, however, a growing number of reports have further acknowledged
important contributions played by membrane lipids in the process of signal
transduction. RECENT FINDINGS: In particular, the constituency of membrane lipids
can regulate how proteins with SH2 domains and molecules like K-Ras expose their
catalytic domains to the cytosol and interact with effectors and second
messengers. Recent reports have also shown that the degree of saturation of
phospholipids can reduce the activation of certain G-protein-coupled receptors,
and signaling downstream to Toll-like receptor 4 with consequences to nuclear
factor kappa B activation and inflammation. Levels of specific gangliosides in
the membrane were reported to activate integrins in a cell-autonomous manner
affecting tumor cell migration. Furthermore, high resolution of the association
of cholesterol with the smoothened receptor has clarified its participation in
sonic hedgehog signaling. These are some of the key advancements that have
further propelled our understanding of the broad versatile contributions of
membrane lipids in signal transduction. SUMMARY: As we gain definitive detail
regarding the impact of lipid-protein interactions and their consequences to cell
function, the options for therapeutic targeting expand with the possibility of
greater specificity.
PMID- 28692599
TI - Cavitary Choroidal Metastasis from Clear Cell Renal Cell Carcinoma.
AB - PURPOSE: To report the clinical, funduscopic, and echographic features of a
choroidal metastatic tumor from a clear cell renal cell carcinoma presenting with
intralesional cavitation. CASE REPORT: An 81-year-old man with history of clear
cell renal cell carcinoma presented with blurred vision. A clinical examination
including standardized ultrasound was performed, which revealed a choroidal mass
with cystic-like cavitation. The patient underwent brachytherapy with regression
of the tumor. CONCLUSIONS: We report the features of a cavitary choroidal
metastasis from clear cell renal cell carcinoma. Occurrence of features usually
associated with uveal melanoma in a patient with a metastatic choroidal tumor may
lead to misdiagnosis.
PMID- 28692600
TI - Relationship of Lymph Node Micrometastasis and Micropapillary Component and Their
Joint Influence on Prognosis of Patients With Stage I Lung Adenocarcinoma.
AB - This study aimed to investigate the relationship between lymph node
micrometastasis and histologic patterns of adenocarcinoma, with a particular
focus on their joint effect on prognosis. We retrospectively reviewed 235
patients with stage I adenocarcinoma from January 2009 to December 2009. Lymph
node micrometastasis was evaluated by immunohistochemical staining for
cytokeratin (AE1/AE3) and thyroid transcription factor-1. A logistic regression
model was applied to confirm the predictive factors of micrometastasis. Survival
analysis was performed to evaluate the effect of micrometastasis on prognosis.
Lymph node micrometastasis was observed in 35 patients (15%). Patients with
micrometastasis had significantly worse recurrence-free survival (P<0.001) and
overall survival (P<0.001) compared with those without micrometastasis.
Micropapillary component was confirmed as an independent predictor of increased
frequency of micrometastasis (P<0.001). Among 62 patients with adenocarcinoma
with a micropapillary component, 23 (37%) had lymph node micrometastasis.
Micropapillary-positive/micrometastasis-positive patients had significantly worse
survival compared with micropapillary-positive/micrometastasis-negative patients
(RFS, P=0.039; OS, P=0.002) and micropapillary-negative patients (recurrence-free
survival, P<0.001; overall survival, P<0.001). Moreover, the presence of
micrometastasis correlated with a higher risk of locoregional recurrence
(P=0.031) rather than distant recurrence (P=0.456) in micropapillary-positive
patients. In summary, lymph node micrometastasis was more frequently observed in
adenocarcinoma with a micropapillary component. Moreover, lymph node
micrometastasis could provide helpful prognostic information in patients with
resected stage I lung adenocarcinoma with a micropapillary component; thus,
immunohistochemical detection of micrometastatic tumor cells in lymph nodes
should be recommended.
PMID- 28692602
TI - Lipidic Overload (Ice Cream) Does Not Change Parameters of Coagulation and Blood
Viscosity.
PMID- 28692601
TI - Recurrent BRAF Gene Rearrangements in Myxoinflammatory Fibroblastic Sarcomas, but
Not Hemosiderotic Fibrolipomatous Tumors.
AB - Myxoinflammatory fibroblastic sarcoma (MIFS) is a low grade soft tissue sarcoma
with a predilection for acral sites, being associated with a high rate of local
recurrence but very infrequent distant metastases. Although a t(1;10)
translocation resulting in TGFBR3-MGEA5 fusion has been reported as a recurrent
genetic event in MIFS, this abnormality is seen only in a subset of cases. As no
studies to date have investigated the spectrum of alternative genetic alterations
in TGFBR3-MGEA5 fusion negative MIFS, we undertook a genetic analysis of this
particular cohort for further molecular classification. Triggered by an index
case occurring in the finger of a 37-year-old female and harboring a novel TOM1L2
BRAF fusion by targeted RNA sequencing we investigated potential recurrent BRAF
abnormalities by screening a large group of 19 TGFBR3-MGEA5 fusion negative MIFS
by fluorescence in situ hybridization. There were 6 (32%) additional MIFS with
BRAF genetic abnormalities, including 5 gene rearrangements and one showing BRAF
amplification. Interestingly, VGLL3 amplification, a recurrent genetic
abnormality coexisting with t(1;10) in some MIFS, was also detected by
fluorescence in situ hybridization in 4/6 (67%) BRAF-rearranged MIFS, but not in
the BRAF-amplified case. Up-regulated VGLL3 mRNA expression was also demonstrated
in the index case by RNA sequencing. The 7 BRAF-rearranged/amplified MIFS arose
in the fingers (n=3), and 1 each in wrist, forearm, foot, and knee, of adult
patients (36 to 74 y; M:F=4:3). The histologic spectrum ranged from predominantly
solid growth of plump histiocytoid to epithelioid tumor cells with focal myxoid
change to a predominantly myxoid background with scattered tumor cells. Varying
degree of inflammatory infiltrates and large tumor cells with virocyte-like
macronucleoli were observed in most cases. Immunohistochemical stains of
phosphorylated ERK, a downstream effector of BRAF activation, were positive in
all 4 cases tested (2 diffuse strong, 2 focal strong). Unlike t(1;10), BRAF
rearrangements were only found in MIFS but not in 6 hemosiderotic fibrolipomatous
tumor (HFLT) lacking TGFBR3-MGEA5 fusions (including 2 pure HFLT, 2 hybrid HFLT
MIFS, and 2 associated with pleomorphic hyalinizing angiectatic tumors).
PMID- 28692603
TI - Repair of a Hemiforehead Defect With Exposed Bone.
PMID- 28692604
TI - Determining the Differential Effects of Stretch and Growth in Tissue-Expanded
Skin: Combining Isogeometric Analysis and Continuum Mechanics in a Porcine Model.
AB - BACKGROUND: The relative effects of skin growth and stretch during tissue
expansion have not been studied. The authors use novel analytic techniques that
allow calculation of these factors at any point of a skin patch. OBJECTIVE: The
authors sought to determine how stretch and growth change with different
expansion rates and to correlate these values with histologic and cellular
changes in skin. MATERIALS AND METHODS: Two minipigs were implanted with a total
of 5 tissue expanders under tattooed skin grids. One pig was expanded over 35
days and the second over 15 days. Isogeometric analysis allowed calculation of
growth and stretch. Expanders with similar total deformation were compared
between protocols. Regression analysis determined predictive effects of stretch
and growth on histologic data from the second animal. RESULTS: Deformation was
more attributable to stretch in rapid than in slow expansion (1.40 vs1.12, p <
.001). Growth was higher in slow expansion than in rapid (1.52 vs 1.07, p <
.001). Both growth and stretch predicted epidermal thickness, dermal thinning,
and keratinocyte proliferation. Growth predicted vascularity. CONCLUSION:
Isogeometric analysis allows determination of precise surface area changes for
correlation to microscopic-level data. Using the model, the authors identified
that skin deformation in rapid expansion is more attributable to stretch.
PMID- 28692605
TI - Examining the Relationship Between Symptomatic Burden and Self-reported
Productivity Losses Among Patients With Uterine Fibroids in the United States.
AB - OBJECTIVE: To evaluate the impact of uterine fibroid symptoms on employment and
household productivity. METHODS: An online survey of US women between 18 and 54
was conducted. Productivity was assessed using the health related productivity
questionnaire (HRPQ). Descriptive statistics and logistic multivariable
regressions examined the relationship between uterine fibroids (UF) symptom
experience and employment and household productivity. RESULTS: Of 1365 eligible
women, 873 (64.0%) were employed. Women lost an average of 0.8 hours to
employment-related absenteeism and 4.4 hours due to employment-related
presenteeism for 5.1 hours of employment productivity lost/week. Women lost an
average of 1.4 hours due to household-related absenteeism and 1.6 hours due to
household-related presenteeism for a total of 3.0 hours of household lost
productivity. Productivity losses increased with increases in symptom burden.
CONCLUSION: UF has a substantial impact on employment-related and household
related productivity.
PMID- 28692606
TI - Occupational Health and the Performing Arts: An Introduction.
AB - OBJECTIVE: Workplace hazards in the performing arts cause injuries, disabilities,
and deaths every year. Occupational health professionals are familiar with most
of these hazards and are particularly qualified to contribute to efforts to
reduce them. This article reviews current health issues in the performing arts
and highlights opportunities for occupational health contributions. METHODS:
Recognized experts in performing arts medicine were consulted and articles
illustrating performing arts health issues were reviewed. Literature sources
included medical databases, unindexed art-health publications, and popular press
articles. RESULTS: Resources discussing hazards and health issues in theater,
dance, voice, and instrumental musicians were located and reviewed. CONCLUSIONS:
Treatment providers have a history of involvement with segments of the performing
arts. The occupational health approach to workplace health issues can effectively
complement these efforts. Sources of further information on performing arts
health concerns are available.
PMID- 28692607
TI - Exposure to Work and Nonwork Stressors and the Development of Heart Disease Among
Canadian Workers Aged 40 Years and Older: A 16-year Follow-up Study (1994 to
2010).
AB - OBJECTIVE: The aim of this study was to evaluate the contribution of work,
nonwork, and individual factors to self-reported heart disease, and to evaluate
gender-related differences over a period of 16 years among Canadian workers aged
40 years and more. METHODS: Using the National Population Health Survey (NPHS,
1994 to 2010), we estimated multilevel logistic regression models (N = 2996).
RESULTS: Couple-related strains, being a man, age, hypertension, and body mass
index, are associated with an increased risk of heart disease. In analysis
stratified by gender, physical demands at work and having high child-related
strains were associated with heart disease specifically among women. Psychotropic
drug use increased the risk of heart disease only in men. CONCLUSION: Our study
suggests that work stressors measured by Statistics Canada NPHS are largely not
associated with the risk of heart disease, except in women exposed to physical
demands at work.
PMID- 28692608
TI - Is Active Commuting to Work Related to Work Performance Among Male Office
Workers?
AB - OBJECTIVE: This study aimed to elucidate the association between active commuting
to work (ACW) and work performance among male office workers. METHODS: This cross
sectional study included 331 male office workers (age 44.0 +/- 11.5 years), with
ACW assessed on a self-reported questionnaire and then categorized into non-ACW
(0 to 19 minutes) and ACW (>=20 minutes). Work performance [World Health
Organization Health and Work Performance Questionnaire (HPQ)] was categorized as
high (>=50) and low (<50). Multiple logistic regression models were used to
examine the association between ACW and HPQ. RESULTS: We found that 42.2%
respondents adopted ACW. After adjusting for demographic data, lifestyle factors,
and depressive symptoms, ACW was significantly associated with high HPQ (odds
ratio: 2.43; 95% confidence interval: 1.30 to 4.54). CONCLUSIONS: In male office
workers, ACW was independently associated with higher work performance.
PMID- 28692609
TI - Human Semen Quality, Sperm DNA Damage, and the Level of Reproductive Hormones in
Relation to Urinary Concentrations of Parabens.
AB - OBJECTIVE: The aim of this study was to evaluate the association between
environmental exposure to parabens and semen quality parameters [main semen
parameters, computer-aided semen analysis (CASA parameters], sperm chromatin
structure, and the level of reproductive hormones in men [follicle-stimulating
hormone (FSH), testosterone, estradiol]. METHODS: Urine samples collected from
315 men who attended the infertility clinic for diagnostic purposes with normal
semen concentration of 15 to 300 mln/mL were analyzed for five parabens
concentrations using a validated gas chromatography ion-tap mass spectrometry
method. Participants were interviewed and also provided a semen, saliva, and
blood samples. RESULTS: Urinary parabens concentrations were significantly
associated with an increase in the percentage of sperm with abnormal morphology,
in sperm with high DNA stainability and a decrease in the percentage of motility
and testosterone level. CONCLUSIONS: This is one of the first study on this
topic, so the observation of the relationship between parabens and semen quality
warrants further investigation.
PMID- 28692610
TI - Work Enabling Opioid Management.
AB - OBJECTIVE: This study describes the relationship between opioid prescribing and
ability to work. METHODS: The opioid prescription patterns of 4994 claimants were
studied. Three groups were constructed: 1) at least 3 consecutive months
prescribed (chronic opioid therapy; COT); 2) less than 3 consecutive months
prescribed (acute opioid therapy; AOT); and 3) no opioids prescribed. Variables
included sex, age, daily morphine equivalent dose (MED), days opioids were
prescribed, temporary total days (TTDs), and medical/indemnity/total costs.
RESULTS: The COT versus AOT claimants had higher opioid costs ($8618 vs $94),
longer TTD (636.2 vs 182.3), and average MED (66.8 vs 34.9). Only 2% of the COT
cohort were not released to work. Fifty-seven percent of patients in the COT
category (64 of 112) were released to work while still receiving opioids.
CONCLUSION: COT does not preclude ability to work when prescribing within
established guidelines.
PMID- 28692611
TI - A National Survey on the Use of Electronic Directly Observed Therapy for
Treatment of Tuberculosis.
AB - CONTEXT: An increasing number of tuberculosis (TB) programs are adopting
electronic directly observed therapy (eDOT), the use of technology to supervise
patient adherence remotely. Pilot studies show that treatment adherence and
completion were similar with eDOT compared with the standard in-person DOT.
OBJECTIVE: In December 2015, the National Tuberculosis Controllers Association
administered an online survey to determine the extent to which eDOT is used in
the United States. PARTICIPANTS: Sixty-eight Centers for Disease Control and
Prevention (CDC)-funded health department TB programs across the United States
and a convenient sample of local health department TB programs. RESULTS: Fifty
six (82%) of 68 CDC-funded health department TB programs and an additional 57
local TB programs responded to the survey. Forty-seven (42%) of 113 TB programs
are currently using eDOT, 41 (36%) are planning to implement it in the next year,
and 25 (22%) have no plans to implement eDOT. Of the 47 TB programs using eDOT,
31 (66%) use synchronous video DOT, 4 (9%) asynchronous video DOT, 11 (23%) a
combination of both, and 1 (2%) ingestible sensor to conduct electronic
observations. Forty-one (87%) indicated that treatment adherence and 40 (85%)
indicated that treatment completion were about the same or higher than in-person
DOT. More than 80% indicated that eDOT resulted in program cost savings, and
almost all (91%) reported benefits in patient and staff satisfaction. However, 25
(53%) of the 47 TB programs that use eDOT encountered technical challenges and 37
(79%) offer eDOT to less than a third of their patients. CONCLUSIONS: Results
from this survey indicate that eDOT is a promising tool that can be utilized to
efficiently and effectively manage TB treatment. Findings will inform other TB
programs interested in implementing eDOT. However, further evaluation is needed
to assess eDOT acceptability to understand barriers to eDOT implementation from
the patient and provider perspectives.
PMID- 28692612
TI - Occupational Safety and Health and Healthy Housing: A Review of Opportunities and
Challenges.
AB - PURPOSE: Occupational safety and health (OSH) risks in construction of healthy
housing (HH) have not been examined and collaboration between HH and OSH
professionals is inadequate. The World Health Organization is developing
international HH guidelines and the International Labour Organization is working
to improve OSH in construction globally. METHODS: We searched for exemplary
reports (including gray literature) on construction hazards; preventive measures
for occupants and workers; OSH frameworks, laws, and regulations; definitions;
and HH. RESULTS: Healthy housing construction typically improves ventilation,
moisture and mold, pest control, injury hazards, cleanability, maintenance,
accessibility, thermal conditioning, and avoidance of toxic building materials.
To date, this work is done without explicit requirements for worker health.
Construction is among the most hazardous sectors around the globe, although
protective measures are well known, including engineering and administrative
controls and provision of personal protective equipment. Residential
construction, renovation, repair, and maintenance are fragmented, consisting
mostly of small companies without proper OSH training, equipment, and knowledge
of HH principles. Residential construction is often undertaken by informal or
unauthorized workers, putting them at high risk. Reduced exposure to toxic
building materials is an example of a benefit for both workers and occupants if
OSH and HH collaboration can be improved. By recognizing that homes under new
construction or renovation are both a workplace and a residence, HH and OSH
initiatives can apply public health principles to occupants and workers
simultaneously. This article publishes key definitions, hazards and interventions
common to both fields. CONCLUSIONS: A global increase in residential construction
and renewed global interest in HH poses both risks and opportunities for primary
prevention. Policy and practice interventions can benefit the health of occupants
and those who work on their homes. Improvements in legislation, regulation, and
international frameworks are needed to maximize OSH and HH collaboration and
realize significant cobenefits. Occupational safety and health and HH standards
should include requirements to protect both workers and occupants. Because homes
can also be workplaces, both workers and housing occupants will receive important
cobenefits when OSH and HH standards use proven interventions to protect workers
and occupants.
PMID- 28692613
TI - Associations Among Cardiometabolic Abnormalities, Obesity, and Sociobehavioral
Factors in a Southern Nevada Adult Population.
AB - CONTEXT: Cardiometabolic abnormalities underlie many health risks associated with
obesity. OBJECTIVE: We determined the relationship between cardiometabolic
abnormalities, sociodemographic characteristics, and modifiable risk factors
among adults in Southern Nevada. DESIGN: We included 2415 participants older than
20 years from the Behavioral Risk Factor Surveillance System surveys conducted in
2011, 2013, and 2015 in Southern Nevada. Cardiometabolic abnormalities were
assessed on the combined basis of blood pressure, cholesterol, and diabetes
status. Logistic regression stratified by body mass index status was used to
examine cardiometabolic abnormalities in different body mass index classes. MAIN
OUTCOME MEASURE: Odds ratio estimates for cardiometabolic abnormalities after
accounting for sociodemographic and health behavior characteristics. RESULTS:
Cardiometabolic abnormalities followed a socioeconomic gradient, although
adjustment for lifestyle variables attenuated the associative link. Non-Hispanic
black (vs white) race did not elevate cardiometabolic abnormalities risk among
nonobese adults, yet conferred a multivariable-adjusted odds ratio of 2.18 (95%
confidence interval [CI], 1.03-4.61) among obese adults. By comparison, odds of
cardiometabolic abnormalities among nonobese adults were 2.42 (95% CI, 0.99-5.92)
times higher for Hispanics and 2.83 (95% CI, 1.23-6.55) times higher for other or
multiracial minorities. Among obese adults, male gender (odds ratio: 1.84; 95%
CI, 1.03-3.27) and former (odds ratio: 2.09; 95% CI, 1.14-3.85) smoker status
were associated with cardiometabolic abnormalities independent of other
covariates. CONCLUSIONS: The present data support intervention strategies
tailored to reinforce and promote positive health behaviors among disadvantaged
groups. There were variable patterns of ethnic group disparities in clustered
cardiometabolic abnormalities across body mass index classes. Targeted prevention
approaches incorporating an explicit health equity perspective may help mitigate
observed differences.
PMID- 28692614
TI - Keeping Your Compass Pointed North.
PMID- 28692615
TI - Hypertonic Saline for ICP Reduction in Traumatic Brain Injury Patients: An
Evolving Practice.
PMID- 28692616
TI - Development of a Falls Registry: A Pilot Study.
AB - Each year approximately 1 in 4 healthy older adults aged 65+ years and 1 in 2
aged 80+ years living in the community will fall. Fall-related injuries are the
leading cause of death and disability and cost the United States approximately
$31 billion annually. Currently, no repository of scene data exists that informs
prevention programs regarding circumstances that contribute to older adult falls.
This was a multicenter (4 sites: Kansas, Maryland, Oregon, and Texas) pilot study
consisting of interviews of older (55+ years) patients who had been admitted to a
trauma center with fall-related injuries. Questions included information
regarding environment, behaviors, injuries, and demographics. Additional
information was abstracted from patient medical record: comorbidities,
medications, and discharge information. Data are presented descriptively. Forty
nine patients were interviewed: average age was 78 years; White (93.9%); female
(53.1%); and most (63.3%) had fallen before. The most commonly reported fall
factors and injuries included those occurring at home without agency services
(65.0%), on hard flooring (51.1%), with laced shoes (44.2%), and with walkers
(36.7%) and contained contusion/open wound of head (61.2%). Survey time was
anecdotally estimated at 10-15 min. Preliminary data suggest that prevention
efforts should emphasize on educating older adults to focus on ambulation, body
position, and use of assistive devices in their daily activities. The development
of a systematic and organized registry that documents scene data would inform
public health agencies to develop fall prevention programs that promote older
adult safety. Furthermore, it would provide a large sample size to test factor
associations with injury severity.
PMID- 28692617
TI - Impact of Pharmacy Students on a Level II Trauma Center.
AB - This study aims to quantify the benefits of allowing advanced pharmacy practice
experience (APPE) students to make medical interventions while on rotation by
analyzing their interventions made and the resulting cost avoidance. This
retrospective, observational cohort study was completed using self-reported data
of APPE student interventions made at a Level II trauma center, under the
supervision of a clinical pharmacist. Interventions were analyzed for their
impact on patient care and cost avoidance through a comprehensive literature
search and online Quantifi reference. A total of 187 interventions over a 7-month
study period resulted in an estimated cost avoidance of $26,175. Advanced
pharmacy practice experience students acting as pharmacist extenders resulted in
a monthly cost avoidance of $3,739, which corresponds to $44,871 per year.
Incorporating student pharmacists as active members of an interprofessional team
enhanced patient care by increasing medical interventions, leading to increased
cost avoidance by optimizing medication regimens.
PMID- 28692619
TI - Effects of a Systematic Quality Improvement Process to Decrease Complications in
Trauma Patients With Prehospital Peripheral Intravenous Access.
AB - Peripheral intravenous (PIV) catheterization is commonly performed, and its
complications are costly, may result in serious health issues, and may adversely
affect patient satisfaction. At our large urban Level I trauma center, we
identified a cluster of 7 PIV complications from prehospital insertions in a 5
month period. Several of the patients developed noninfectious as well as
infectious, limb-threatening complications requiring aggressive operative
intervention. A performance improvement project was chartered to identify the
cause of PIV complications and review current nursing practice. The FOCUS-Plan Do
Check Act methodology was used to measure and improve practice. With
implementation of interventions and outcomes monitoring, no PIV complications
were reported for the subsequent 39 consecutive months. Our findings have
implications for more controlled studies to establish best practice at other
Level I trauma centers across the country.
PMID- 28692620
TI - Delirium in the ICU: What About the Floor?
AB - Delirium was first described in the 1800s as acute, fluctuating confusion. Recent
studies note an incidence of 15% in adult intensive care unit patients. Here we
present the first prospective study to evaluate the incidence and risk factors
for delirium in patients admitted to the trauma surgeon (TS) in non-critical care
areas (NCCAs). Patients 18 years or older admitted to any TS in the designated
NCCA were evaluated and consented for participation over a 3-month period.
Participants were screened with the Confusion Assessment Method (CAM) every 12
hr. Those positive for delirium (CAM+) were administered the CAM-Severity. In
addition, 69 other previously identified risk factors were evaluated. Over 3
months, 148 patients were evaluated, 12 of whom were CAM+ (8%). Of patients 65
years or older, 21% screened positive for delirium. Age, education level,
presence of Foley catheter, respiratory distress, orthopedic operation, and lack
of ambulation were risk factors associated with delirium (p < .05). Among all TS
patients in the NCCA, we found delirium to be present in 8%. Our nurses
identified a 21% incidence of delirium in patients 65 years or older. Given this
significant incidence, screening at-risk patients in the NCCA should be
considered.
PMID- 28692621
TI - Challenges in the Management of Geriatric Trauma: A Case Report.
AB - This article describes geriatric trauma and commonly associated difficulties
emphasizing both the epidemiology and assessment of geriatric trauma. There is
little data guiding decisions for trauma patients 65 years or older, as there are
many unique characteristics to the geriatric population, including comorbidities,
medications, and the aging physiology. The geriatric population in the United
States has been steadily climbing for the last 20 years and is projected to
continue on this trend. Although each patient presents differently, there remains
a need for the consistent utilization of standard guidelines to help dictate care
for geriatric patients, particularly for patients not receiving care at a trauma
center. This review uses a case study about an elderly woman with many
comorbidities, followed by a comprehensive discussion of geriatric trauma and the
challenges that result from a lack of guideline utilization to direct management.
PMID- 28692623
TI - A Retrospective Cohort Study of Traumatic Brain Injury and Usage of Protective
Headgear During Equestrian Activities.
AB - Some of the more popular sporting activities for those living in rural areas
include equestrian activities such as rodeo events and horseback riding. The lack
of helmet use poses a concern for those who participate in these activities due
to the risk of sustaining a traumatic brain injury (TBI) and ultimately having a
negative effect on their future. A retrospective cohort study was conducted at a
trauma center comparing the data on animal-riding patients and their use or lack
of use of headgear and incidence of TBI. Of the patients identified, 16.2%
sustained a head injury, ranking TBI fourth among all injuries sustained by the
animal-riding population. Males were predominantly affected; however, females of
pediatric age 5-17 years (54.5%) ranked high among the TBI population. Among all
the patients identified with TBI, none of the patients were wearing a helmet and
all sustained a head injury. The average injury severity score was 11, with
hospital length of stay averaging less than 2 days and the overall mortality was
3.6%. Findings from the study should be considered for the purpose of
implementing an age-specific educational program focused on head injury
prevention and utilization of protective headgear. Current literature supports
the use of protective headgear to reduce the risk of head injuries. Animal riders
should be educated on the importance of using headgear as a preventive measure.
Future studies are needed to indicate the effectiveness of injury prevention in
regard to head injury severity and the use of protective headgear.
PMID- 28692624
TI - Improving Trauma Care in Africa.
AB - Bringing the first Advanced Trauma Care for Nurses (ATCN) provider and instructor
courses to Zimbabwe was the initial step in an educational partnership spanning
more than 8,000 miles. Zimbabwe is a South African country with limited health
care services, severe financial restraints, and a shortage of health care
professionals. All of these barriers made our goal of bringing an organized and
systematic approach to trauma care even more important. The nurses of Zimbabwe
were aware that their patients were not receiving "best practice" care, which
made them passionate for education, with strict enforcement of standardized
delivery of care. The ATCN course provided the foundation for building a
comprehensive approach to trauma care and creating a systematic and rapid initial
assessment process during primary treatment of injured patients. Collaboration
with the American College of Surgeons for the ATLS component was critical to the
success and sustainability. The ultimate goal was to reduce morbidity and
mortality from traumatic injuries and ultimately provide a sustained continuing
education program to nurses countrywide. In November 2015, the Zimbabwe Nursing
Council certified St. Philip's as its official National Nurse Trauma Training
Center, the first and only center of its kind in Africa. As of October 2016, a
total of 64 nurses have completed the ATCN courses and 9 have been checked off as
ATCN faculty. Our goal was realized through the cooperation of many individuals.
The nurses of Africa received the training crucial to delivering an excellent
standard of care and ultimately saving lives.
PMID- 28692625
TI - A New Craniothoracic Mattress for Immobilization of the Cervical Spine in
Critical Care Patients.
AB - Current immobilization techniques of the cervical spine are associated with
complications including pressure ulcers, discomfort, and elevated intracranial
pressures with limited access to the thorax and airway. In this study, a newly
developed craniothoracic immobilizer (Pharaoh mattress) for critical care
patients with cervical injury was tested for its restriction of cervical
movement, peak interface pressures, comfort, and radiolucency, and compared with
headblocks strapped to a spineboard. Cervical movement was measured by roentgen
stereophotogrammetric analysis in 5 fresh frozen cadavers. Peak interface and
discomfort pressures were measured in 10 healthy volunteers. Radiographic
absorption was calculated by measuring the total emission radiation with and
without immobilizer. The Pharaoh mattress caused a mean restriction of 59% (SD:
15) flexion-extension, 77% (SD: 14) lateral bending, and 93% (SD: 3) rotation,
compared with the unrestricted situation. No significant differences in
restriction of cervical movement were found between headblocks strapped to a
spineboard and the Pharaoh mattress. The mean peak pressures on the Pharaoh
mattress were significantly lower than on the spineboard. Healthy volunteers gave
significantly lower numeric discomfort scores on the Pharaoh mattress than on the
spineboard. The Pharaoh mattress absorbed more x-rays than the spineboard. The
Pharaoh mattress provides similar restriction of cervical movement compared with
headblocks strapped to a spineboard but with lower interface pressures and
increased comfort. This new mattress could be useful for immobilization of the
cervical spine in critical care patients with mechanically instable spinal
fractures.
PMID- 28692626
TI - A Literature Review on Gang Violence.
AB - Gangs and gang violence are a concerning cause of preventable injuries and death
in the trauma community. The number of gangs and gang members has been on an
upward trend since 2003 with an estimated 30,000 gangs in the United States. This
includes approximately 850,000 gang members. Trauma centers are in a unique
position to participate in the prevention of gang violence. This review compiles
current, relevant literature on gangs and gang violence covering the following
topics: prevention/intervention, contributing influences, and experiential
reflections. The purpose of the literature review is to deepen understanding of
gangs and gang violence and potentiate further research in this area in order to
help promote successful prevention efforts. Trauma nurses can use this
information in developing culturally sensitive, compassionate care and trauma
centers will find this useful in the development of injury prevention programs
aimed at the reduction of gang and street violence.
PMID- 28692627
TI - Emotional Intelligence and the Occurrence of Accidents in Motorcycle Drivers in
Kashan, Iran.
AB - There is an inherent risk of death and injury for motorcyclists. Some factors
such as personality and psychological characteristics may be contributors of
motor vehicle accidents/crashes. This study aimed to determine the relationship
between emotional intelligence and its related components and the occurrence of
accidents/crashes in motorcycle drivers. In this case-control study, 280
motorcycle drivers with and without a history of motorcycle-related accidents or
crashes in Kashan, Iran, were selected for convenience sampling. The tool used
was the Bar-On Emotional Intelligence Questionnaire and included 90 items.
Logistic regression revealed that components of emotional intelligence identified
as happiness, optimism, flexibility, self-actualization, autonomy, and
interpersonal relationships were different between motorcycle drivers with and
without an accident/crash. Our findings emphasized the important role of
developing and enhancing the skills of emotional intelligence as related to the
prevention of accidents/crashes.
PMID- 28692628
TI - Genetic determinants of impaired awareness of hypoglycemia in type 1 diabetes.
AB - OBJECTIVE: It is likely that impaired awareness of hypoglycemia (IAH) and severe
hypoglycemia are in part determined by genetic factors. The aim of this study was
to investigate candidate genes for associations with IAH and severe hypoglycemia
in a cohort of patients with type 1 diabetes. PARTICIPANTS AND METHODS:
Consecutive patients with type 1 diabetes were genotyped for single-nucleotide
polymorphisms in or near the genes for the beta1 and beta2 adrenergic receptor
(ADRB1, ADRB2), SORCS1, and BNC2, and for the insertion/deletion polymorphism in
the ACE gene. IAH and severe hypoglycemia were assessed using a validated
questionnaire. RESULTS: Of 486 patients, 32.5% were classified as having IAH. The
Arg16Gly polymorphism of ADRB2 was associated with IAH (odds ratio: 1.49, 95%
confidence interval: 1.01-2.20, P=0.046) Gly16 (GG) versus carriers of the A
allele. In a haplotype analysis, the association was the highest in patients with
GG at position 16 and heterozygous at position 27 (odds ratio: 2.19, 95%
confidence interval: 1.33-3.61, P=0.03). There were no associations between IAH
and other genes, and none of the studied genes was associated with severe
hypoglycemia. CONCLUSION: Genotypes at two variants of ADRB2 are associated with
IAH. This association is comparable with the risk of classical risk factors for
IAH.
PMID- 28692629
TI - Physical Activity Dimensions Associated with Impaired Glucose Metabolism.
AB - PURPOSE: Physical activity (PA) is important in the prevention of Type 2
diabetes, yet little is known about the role of specific dimensions of PA,
including sedentary time in subgroups at risk for impaired glucose metabolism
(IGM). We applied a data-driven decision tool to identify dimensions of PA
associated with IGM across age, sex, and body mass index (BMI) groups. METHODS:
This cross-sectional study included 1501 individuals (mean (SD) age, 65.6 (6.8)
yr) at high risk for Type 2 diabetes from the ADDITION-PRO study. PA was measured
by an individually calibrated combined accelerometer and heart rate monitor worn
for 7 d. PA energy expenditure, time spent in different activity intensities,
bout duration, and sedentary time were considered determinants of IGM together
with age, sex, and BMI. Decision tree analysis was applied to identify subgroup
specific dimensions of PA associated with IGM. IGM was based on oral glucose
tolerance test results and defined as a fasting plasma glucose level of >=6.1
mmol.L and/or a 2-h plasma glucose level of >=7.8 mmol.L. RESULTS: Among
overweight (BMI >=25 kg.m) men, accumulating less than 30 min.d of moderate-to
vigorous PA was associated with IGM, whereas among overweight women, sedentary
time was associated with IGM. Among individuals older than 53 yr with normal
weight (BMI <25 kg.m), time spent in light PA was associated with IGM. None of
the dimensions of PA were associated with IGM among individuals <=53 yr of age
with normal weight. CONCLUSIONS: We identified subgroups in which different
activity dimensions were associated with IGM. Methodology and results from this
study may suggest a preliminary step toward the goal of tailoring and targeting
PA interventions aimed at Type 2 diabetes prevention.
PMID- 28692630
TI - Effects of Four Weeks of Strength Training on the Corticomotoneuronal Pathway.
AB - PURPOSE: Neural adaptations to strength training have long been recognized, but
knowledge of mechanisms remains incomplete. Using novel techniques and a design
which limited experimental bias, this study examined if 4 wk of strength training
alters voluntary activation and corticospinal transmission. METHODS: Twenty-one
subjects were randomized into strength training (n = 10; 7 females, 3 males; 23.5
+/- 7.5 yr; mean +/- SD) and control groups (n = 11; 2 females, 9 males; 23.0 +/-
4.2 yr). Strength training involved 12 sessions of high-force isometric
contractions of the elbow flexors. Before and after training, voluntary
activation of the elbow flexors was assessed via transcranial magnetic
stimulation. Also, for the first time, magnetic stimulation of corticospinal
axons was used to examine spinal-level adaptations to training. The evoked
responses, termed cervicomedullary motor-evoked potentials (CMEPs), were acquired
in resting biceps brachii in three arm postures. Muscle adaptations were assessed
via electrical stimulation of biceps. RESULTS: Compared with the control group,
the strength training group exhibited greater increases in maximal strength
(12.8% +/- 6.8% vs 0.0% +/- 2.7%; P < 0.001), biceps electromyographic activity
(27.8% +/- 25.9% vs -5.2% +/- 16.8%; P = 0.002), and voluntary activation (4.7%
+/- 3.9% raw change vs -0.1% +/- 5.2%; P = 0.034). Biceps CMEPs in all arm
postures were unchanged after training. Biceps twitch characteristics were also
unchanged. CONCLUSIONS: Four weeks of isometric strength training of the elbow
flexors increased muscle strength and voluntary activation, without a change in
the muscle. The improvement in activation suggests that voluntary output from the
cortex was better able to recruit motoneurons and/or increase their firing rates.
The lack of change in CMEPs indicates that neither corticospinal transmission nor
motoneuron excitability was affected by training.
PMID- 28692631
TI - Increased Protein Requirements in Female Athletes after Variable-Intensity
Exercise.
AB - PURPOSE: Protein requirements are primarily studied in the context of resistance
or endurance exercise with little research devoted to variable-intensity
intermittent exercise characteristic of many team sports. Further, female
populations are underrepresented in dietary sports science studies. We aimed to
determine a dietary protein requirement in active females performing variable
intensity intermittent exercise using the indicator amino acid oxidation (IAAO)
method. We hypothesized that these requirements would be greater than current
IAAO-derived estimates in nonactive adult males. METHODS: Six females (21.2 +/-
0.8 yr, 68.8 +/- 4.1 kg, 47.1 +/- 1.2 mL O2.kg.min; mean +/- SE) completed five
to seven metabolic trials during the luteal phase of the menstrual cycle.
Participants performed a modified Loughborough Intermittent Shuttle Test before
consuming eight hourly mixed meals providing the test protein intake (0.2-2.66
g.kg.d), 6 g.kg.d CHO and sufficient energy for resting and exercise-induced
energy expenditure. Protein was provided as crystalline amino acid modeling egg
protein with [C]phenylalanine as the indicator amino acid. Phenylalanine turnover
(Q) was determined from urinary [C]phenylalanine enrichment. Breath CO2 excretion
(FCO2) was analyzed using mixed effects biphase linear regression with the
breakpoint and upper 95% confidence interval approximating the estimated average
requirement and recommended dietary allowance, respectively. RESULTS: Protein
intake had no effect on Q (68.7 +/- 7.3 MUmol.kg.h; mean +/- SE). FCO2 displayed
a robust biphase response (R = 0.66) with an estimated average requirement of
1.41 g.kg.d and recommended dietary allowance of 1.71 g.kg.d. CONCLUSIONS: The
protein requirement estimate of 1.41 and 1.71 g.kg.d for females performing
variable-intensity intermittent exercise is greater than the IAAO-derived
estimates of adult males (0.93 and 1.2 g.kg.d) and at the upper range of the
American College of Sports Medicine athlete recommendations (1.2-2.0 g.kg.d).
PMID- 28692632
TI - High Habitual Physical Activity Improves Acute Energy Compensation in Nonobese
Adults.
AB - PURPOSE: Evidence suggests that homeostatic satiety signaling is enhanced with
higher levels of physical activity (PA), with active individuals demonstrating an
improved ability to compensate for previous energy intake (EI). However, prior
studies lacked objective assessment of both PA level and EI. This study examined
the effect of objectively measured PA level on homeostatic (energy compensation)
and hedonic (liking and wanting) responses to high-energy (HEP), low-energy
(LEP), and control preloads. METHODS: Thirty-four nonobese individuals were
grouped by tertiles of accelerometry-measured habitual moderate-to-vigorous PA
(low, LoMVPA; moderate, ModMVPA; high, HiMVPA), similar in age, sex, and body
mass index. After a preliminary assessment, EI (fixed-energy breakfast and ad
libitum lunch, dinner, and evening snack box meals) was determined for three
probe meal days in which preloads varying in energy content (HEP, 699 kcal; LEP,
258 kcal; control, 0 kcal) were consumed before the lunch meal. Liking and
wanting were assessed before and after preload consumption (Leeds Food Preference
Questionnaire), and appetite ratings were taken throughout the day. RESULTS:
Relative to control, EI at lunch was reduced to a greater extent after
consumption of HEP compared with LEP in ModMVPA (P < 0.01) and HiMVPA (P = 0.01)
but not LoMVPA (P = 0.59), reflecting more accurate energy compensation in HiMVPA
and ModMVPA. There were no effects on cumulative EI after preload consumption of
(lunch, dinner, and snack box combined). HEP led to a greater suppression of
hunger, liking, and wanting compared with LEP in all MVPA tertiles. CONCLUSIONS:
Nonobese individuals with lower levels of measured PA were insensitive to the
nutritional manipulation of the preloads, suggesting a weaker satiety response to
food. This study provides objective evidence that higher habitual PA improves
acute homeostatic appetite control.
PMID- 28692633
TI - Outcomes and Cost Analysis of Surveillance Strategies After Initial Treatment for
Women With Recurrent Ovarian Cancer.
AB - OBJECTIVE: The aim of this study was to determine whether there is a survival or
cost benefit dependent on detection strategy of recurrent ovarian cancer (ie,
imaging, physical examination findings, report of symptoms, or rising cancer
antigen 125 [CA-125] levels). METHODS/MATERIALS: A retrospective chart review of
112 ovarian cancer patients was conducted, and method of detection of recurrent
disease was determined from medical records. The following primary outcomes were
determined using Cox proportional hazards regression model: progression-free
survival (PFS) after diagnosis of recurrence and time to death after diagnosis of
recurrence (overall survival [OS]). Several approaches to disease surveillance
were proposed, and a cost model was applied. RESULTS: Median time to recurrence
was 13.5 months. Overall, 6.3% presented with only physical examination findings;
24.1%, with elevating CA-125 levels; 34.8%, with imaging; and 32.1%, with
symptoms. Most patients presenting with recurrent disease diagnosed by rising CA
125 were white (62.9%); those with imaging and symptomatic recurrences were
blacks (56.4% and 57.1%, respectively). There was a small but not statistically
significant OS benefit for recurrence detected via CA-125 (P = 0.85; OS per
detection method: PE, 20.7 months; CA-125, 26.8 months; imaging, 17.8 months; and
symptoms, 6.6 months). We modeled costs of surveillance in our patient cohort; up
to 40.8% of cases of ovarian cancer recurrences would have been missed if no
imaging were obtained during surveillance. CONCLUSIONS: Results indicate minimal
differences in PFS and statistically insignificant differences in OS, depending
on detection method. Notably, black patients with Medicaid presented most often
with symptomatic recurrences, which surprisingly did not affect patient OS and
PFS; and interestingly, pr?ivate or self-pay insurance was associated with
decreased OS among black patients. From our cost analysis, we estimate that the
most cost-effective surveillance strategy for the first year costs $9.2 million
annually and includes office visit biannually, biannual CA-125 levels, and annual
asymptomatic imaging.
PMID- 28692634
TI - Targeting FOXM1 Improves Cytotoxicity of Paclitaxel and Cisplatinum in Platinum
Resistant Ovarian Cancer.
AB - OBJECTIVE: Aberrantly activated FOXM1 (forkhead box protein M1) leading to
uncontrolled cell proliferation and dysregulation of FOXM1 transcription network
occurs in 84% of ovarian cancer cases. It was demonstrated that thiostrepton, a
thiazole antibiotic, decreases FOXM1 expression. We aimed to determine if
targeting the FOXM1 pathway with thiostrepton could improve the efficacy of
paclitaxel and cisplatin in human ovarian cancer ascites cells ex vivo. METHODS:
Human ovarian cancer cell lines and patients' ascites cells were treated with
paclitaxel, cisplatin, and thiostrepton or a combination for 48 hours, and
cytotoxicity was assessed. Drug combination effects were determined by
calculating the combination index values using the Chou and Talalay method.
Quantitative reverse transcriptase-polymerase chain reaction was performed to
determine changes in FOXM1 expression and its downstream targets. RESULTS:
Ovarian cancer cell lines and the patients' ascites cancer cells had an
overexpression of FOXM1 expression levels. Targeting FOXM1 with thiostrepton
decreased FOXM1 mRNA expression and its downstream targets such as CCNB1 and
CDC25B, leading to cell death in both cell lines and patients' ascites cancer
cells. Furthermore, addition of thiostrepton to paclitaxel and cisplatin showed
synergistic effects in chemoresistant ovarian cancer patients' ascites cells ex
vivo. CONCLUSION: Targeting FOXM1 may lead to novel therapeutics for
chemoresistant epithelial ovarian cancer.
PMID- 28692635
TI - Resisting RECIST-Uniformity Versus Clinical Validity.
AB - OBJECTIVES: The Response Evaluation Criteria in Solid Tumors (RECIST)
International Working Group developed criteria for tumor response and progression
to standardize radiological assessment in patients receiving chemotherapy in
phase 2 trials. However, it is unclear whether the defined percentage change in
tumor size and volume reflects true clinical benefit for the patient. The RECIST
criteria were designed to improve objectivity in trials, but not to replace
clinical decision making. The aim of this study was to understand clinicians'
opinions about RECIST in current oncology practice. METHODS: Using Web-based
questionnaires, we investigated attitudes to the use of RECIST at a large
comprehensive cancer center and in an international group of gynecologic cancer
specialists through the Gynecologic Cancer InterGroup. The results reported here
relate to the survey focusing on gynecologic cancer. RESULTS: Sixty medical
professionals from 13 countries responded to the survey. The majority of
respondents worked at a tertiary or specialist cancer center (51; 86%). Overall,
66% of respondents felt RECIST increased trial objectivity and was a good measure
of response. The majority of respondents (81%) reported that they infrequently
challenged RECIST evaluation. Overall, 60% felt more than 10% of patients came
off trial for clinical rather than radiological progression. In the context of a
new small lesion, only 35% felt that should always be considered disease
progression. The importance of both clinician and radiologist input was
highlighted with nontarget progression. Nontarget progression and target
progression were recognized as equally important for clinical decision making
(72%). CONCLUSIONS: RECIST is a key criterion for endpoint assessment in clinical
trials with its value recognized by clinicians. However, this survey also
highlights the practical limitations of RECIST. Disconnect can be seen between
the radiological result and the clinical picture-learning from these patients is
critical. Continued efforts to improve metrics assessing patient benefit in
trials remains a priority.
PMID- 28692636
TI - The Effect of Thymoquinone on Apoptosis of SK-OV-3 Ovarian Cancer Cell by
Regulation of Bcl-2 and Bax.
AB - OBJECTIVE: We aim to determine how cisplatin, thymoquinone (TQ), and combination
regimen can affect apoptosis of cultured SK-OV-3 cells. We also want to explore
the mechanism of these influences on the cells' apoptosis by Bcl-2 and Bax gene.
METHOD/MATERIALS: Cell Counting Kit-8 assay was used to measure the viability of
cultured ovarian cancer cells. Propidium iodide with flow cytometry was used in
cell cycle analysis. Thereafter, we used fluorescein isothiocyanate-stained
annexin V and propidium iodide to detect the effect of cisplatin, TQ, and
combination regimen on apoptosis. Real-time PCR was used to measure the Bcl-2 and
Bax levels. Western blotting was used to measure on protein expression levels of
Bcl-2 and Bax. RESULTS: In Cell Counting Kit-8 assay, we found that inhibitory
effect of TQ was even better than cisplatin, and combination regimen had best
inhibitory effect on cell proliferation. In cell cycle analysis, we found all
regimens had obvious effect to stop cell cycle in S phase. In apoptosis assay, we
found that combination regimen was better to activate cell apoptosis than
cisplatin alone. Combination regimen could decrease expression of Bcl-2 and
increase expression of Bax more than cisplatin or TQ alone. CONCLUSIONS:
Thymoquinone and cisplatin had comparable antitumoric effects on SK-OV-3 cells,
and combination regimen was even better. Thymoquinone could also activate
apoptosis by regulating Bcl-2 and Bax genes. These indicated potential advantage
of TQ for ovarian cancer in clinical practice and suggested future clinical
trials to confirm its effectiveness.
PMID- 28692637
TI - Comparison of 2 Human Chorionic Gonadotropin Immunoassays Commercially Available
for Monitoring Patients With Gestational Trophoblastic Disease.
AB - OBJECTIVE: The aim of this study was to compare serum human chorionic
gonadotropin (hCG) levels in patients with gestational trophoblastic disease
(GTD) using 2 commercially available hCG immunoassays. METHODS: Serum samples
were obtained from patients with GTD attending the Botucatu Medical School
Trophoblastic Diseases Center of Sao Paulo State University (UNESP), from
November 2014 to October 2015. Serum hCG levels were measured with both Architect
i2000SR and Immulite 2000 XPi chemiluminescence assays. Serum hCG levels were
compared against the null hypothesis. Agreement in clinical management decisions
based on the hCG results was determined by comparing baseline hCG measurements
and the hCG curves obtained with both assays. RESULTS: Seventy-three patients
with GTD were included in the analysis. Of these, 45 had hydatidiform mole and
spontaneous remission, whereas 28 had gestational trophoblastic neoplasia (GTN).
There was a perfect (zero difference) agreement in mean hCG levels between
Immulite 2000 XPi and Architect i2000 when hCG is less than 100 mIU/mL. For hCG
values greater than 100 mIU/mL, there was a significant difference between assays
(P < 0.05), with levels measured via Architect i2000SR being higher than those
measured by Immulite 2000 XPi in patients with hydatidiform mole/spontaneous
remission (R = 90%, P < 0.01) and GTN (R = 98%, P < 0.01). Baseline clinical
management decisions showed agreement in 100% (73/37) of cases (kappa = 1.0, P <
0.001), whereas decisions based on hCG curve agreed in 98% (71/72) of cases
(kappa = 0.93, P < 0.001). CONCLUSIONS: Immulite 2000 XPi is the most frequently
recommended assay for diagnosing and monitoring patients with GTD. However, our
results suggest that because Immulite 2000 XPi and Architect i2000 show very
similar performance in measuring hCG levels and in determining clinical
management, Architect may be used as an alternative.
PMID- 28692638
TI - The First Nationwide Multicenter Prevalence Study of Germline BRCA1 and BRCA2
Mutations in Chinese Ovarian Cancer Patients.
AB - OBJECTIVE: Subjects with germline BRCA1/2 mutations (gBRCAm) have an increased
risk of developing ovarian cancer and enhanced sensitivity to platinum-containing
agents and PARP (poly[ADP-ribose] polymerase) inhibitors. BRCA mutations in Asian
patients are poorly understood compared with other populations. We aimed to
investigate gBRCAm prevalence and characteristics in Chinese ovarian cancer
patients. METHODS: We conducted the first nationwide multicenter gBRCAm
prevalence study in China. Eight hundred twenty-six unselected ovarian cancer
patients from 5 clinical centers were enrolled and tested for gBRCAm status.
Medical data including age, family history, previous treatments, clinical
diagnosis, histopathologic diagnosis, tumor grade, platinum sensitivity, and CA
125 test result were reviewed and collected. RESULTS: Prevalence rate or gBRCAm
was determined as 28.5%, with 20.8% of patients harboring BRCA1 mutation and 7.6%
harboring BRCA2 mutation. The group had a higher percentage of high-grade serous
(73.0%), late-stage (III and IV [85.5%]) patients and a younger median age at
diagnosis (52 years) compared with other reported studies. Twnety-seven BRCA1 and
17 BRCA2 mutations have not been reported previously in public databases or the
literature. Statistically significant correlations were observed between gBRCAm
status and family history (P < 0.001), gBRCAm status, and tumor stage (P = 0.02).
A numerical higher prevalence of gBRCAm in patients with high-grade serous
histopathology (30.9%), platinum-sensitive phenotype (34%), and late-line
chemotherapy was observed. CONCLUSIONS: Germline BRCA1/2 mutations is common in
Chinese ovarian cancer patients. This study implies that all ovarian patients
should be tested for gBRCAm status regardless of family history and
histopathology.
PMID- 28692639
TI - Treatment of Myopic Foveoschisis with Air Versus Perfluoropropane: A
Retrospective Study.
AB - BACKGROUND The aim of this study was to compare the efficacy of air and
perfluoropropane (C3F8) combined with vitrectomy to treat myopic foveoschisis
(MF). MATERIAL AND METHODS A retrospective comparison of a consecutive series of
surgical patients was performed. Ninety-seven eyes of 91 patients with MF were
assigned to undergo 23G vitrectomy. After internal limiting membrane (ILM)
peeling, the vitreous cavity was filled with air in 48 eyes of 45 patients (Air
Group). Fluid-air exchange was performed in 49 eyes of 46 patients (C3F8 Group)
followed by an injection of 14% C3F8. Patients were evaluated using best
corrected visual acuity (BCVA) and optical coherence tomography. RESULTS
Preoperatively, there was no significant difference in clinical features between
the groups. After surgery, BCVA was markedly improved and the foveoschisis height
was reduced in both groups compared with baseline (P<0.01), but the difference
between the groups was not significant (P>0.05). No significant differences were
noted in BCVA improvement and retinal restoration (P=0.33 and 0.39, respectively)
in the mild and moderate subgroups (foveoschisis height <=400 MUm) between the
tamponades. However, in the severe group (foveoschisis height >400 MUm), C3F8 had
a more favorable cure rate and foveoschisis height reduction improvement compared
with air (P=0.04 and 0.04, respectively) at the last visit. CONCLUSIONS
Vitrectomy combined with ILM peeling is effective in the treatment of myopic
foveoschisis, and the choice of tamponade depends on the severity of
foveoschisis. Air can be used for patients with a foveoschisis height <=400 MUm,
but C3F8 is more effective for patients with a foveoschisis height >400 MUm.
PMID- 28692640
TI - Congenital toxoplasmosis in Austria: Prenatal screening for prevention is cost
saving.
AB - BACKGROUND: Primary infection of Toxoplasma gondii during pregnancy can be
transmitted to the unborn child and may have serious consequences, including
retinochoroiditis, hydrocephaly, cerebral calcifications, encephalitis,
splenomegaly, hearing loss, blindness, and death. Austria, a country with
moderate seroprevalence, instituted mandatory prenatal screening for toxoplasma
infection to minimize the effects of congenital transmission. This work compares
the societal costs of congenital toxoplasmosis under the Austrian national
prenatal screening program with the societal costs that would have occurred in a
No-Screening scenario. METHODOLOGY/PRINCIPAL FINDINGS: We retrospectively
investigated data from the Austrian Toxoplasmosis Register for birth cohorts from
1992 to 2008, including pediatric long-term follow-up until May 2013. We
constructed a decision-analytic model to compare lifetime societal costs of
prenatal screening with lifetime societal costs estimated in a No-Screening
scenario. We included costs of treatment, lifetime care, accommodation of
injuries, loss of life, and lost earnings that would have occurred in a No
Screening scenario and compared them with the actual costs of screening,
treatment, lifetime care, accommodation, loss of life, and lost earnings. We
replicated that analysis excluding loss of life and lost earnings to estimate the
budgetary impact alone. Our model calculated total lifetime costs of ?103 per
birth under prenatal screening as carried out in Austria, saving ?323 per birth
compared with No-Screening. Without screening and treatment, lifetime societal
costs for all affected children would have been ?35 million per year; the
implementation costs of the Austrian program are less than ?2 million per year.
Calculating only the budgetary impact, the national program was still cost-saving
by more than ?15 million per year and saved ?258 million in 17 years.
CONCLUSIONS/SIGNIFICANCE: Cost savings under a national program of prenatal
screening for toxoplasma infection and treatment are outstanding. Our results are
of relevance for health care providers by supplying economic data based on a
unique national dataset including long-term follow-up of affected infants.
PMID- 28692641
TI - Poor efficacy of preemptive amoxicillin clavulanate for preventing secondary
infection from Bothrops snakebites in the Brazilian Amazon: A randomized
controlled clinical trial.
AB - BACKGROUND: Secondary bacterial infections from snakebites contribute to the high
complication rates that can lead to permanent function loss and disabilities.
Although common in endemic areas, routine empirical prophylactic use of
antibiotics aiming to prevent secondary infection lacks a clearly defined policy.
The aim of this work was to estimate the efficacy of amoxicillin clavulanate for
reducing the secondary infection incidence in patients bitten by Bothrops snakes,
and, secondarily, identify risk factors for secondary infections from snakebites
in the Western Brazilian Amazon. METHODS AND FINDINGS: This was an open-label,
two-arm individually randomized superiority trial to prevent secondary infection
from Bothrops snakebites. The antibiotic chosen for this clinical trial was oral
amoxicillin clavulanate per seven days compared to no intervention. A total of
345 patients were assessed for eligibility in the study period. From this total,
187 accomplished the inclusion criteria and were randomized, 93 in the
interventional group and 94 in the untreated control group. All randomized
participants completed the 7 days follow-up period. Enzyme immunoassay confirmed
Bothrops envenoming diagnosis in all participants. Primary outcome was defined as
secondary infection (abscess and/or cellulitis) until day 7 after admission.
Secondary infection incidence until 7 days after admission was 35.5% in the
intervention group and 44.1% in the control group [RR = 0.80 (95%CI = 0.56 to
1.15; p = 0.235)]. Survival analysis demonstrated that the time from patient
admission to the onset of secondary infection was not different between
amoxicillin clavulanate treated and control group (Log-rank = 2.23; p =
0.789).Secondary infections incidence in 7 days of follow-up was independently
associated to fibrinogen >400 mg/dL [AOR = 4.78 (95%CI = 2.17 to 10.55;
p<0.001)], alanine transaminase >44 IU/L [AOR = 2.52 (95%CI = 1.06 to 5.98; p =
0.037)], C-reactive protein >6.5 mg/L [AOR = 2.98 (95%CI = 1.40 to 6.35; p =
0.005)], moderate pain [AOR = 24.30 (95%CI = 4.69 to 125.84; p<0.001)] and
moderate snakebites [AOR = 2.43 (95%CI = 1.07 to 5.50; p = 0.034)].
CONCLUSIONS/SIGNIFICANCE: Preemptive amoxicillin clavulanate was not effective
for preventing secondary infections from Bothrops snakebites. Laboratorial
markers, such as high fibrinogen, alanine transaminase and C-reactive protein
levels, and severity clinical grading of snakebites, may help to accurately
diagnose secondary infections. TRIAL REGISTRATION: Brazilian Clinical Trials
Registry (ReBec): RBR-3h33wy; UTN Number: U1111-1169-1005.
PMID- 28692642
TI - Hybrid modeling and prediction of dynamical systems.
AB - Scientific analysis often relies on the ability to make accurate predictions of a
system's dynamics. Mechanistic models, parameterized by a number of unknown
parameters, are often used for this purpose. Accurate estimation of the model
state and parameters prior to prediction is necessary, but may be complicated by
issues such as noisy data and uncertainty in parameters and initial conditions.
At the other end of the spectrum exist nonparametric methods, which rely solely
on data to build their predictions. While these nonparametric methods do not
require a model of the system, their performance is strongly influenced by the
amount and noisiness of the data. In this article, we consider a hybrid approach
to modeling and prediction which merges recent advancements in nonparametric
analysis with standard parametric methods. The general idea is to replace a
subset of a mechanistic model's equations with their corresponding nonparametric
representations, resulting in a hybrid modeling and prediction scheme. Overall,
we find that this hybrid approach allows for more robust parameter estimation and
improved short-term prediction in situations where there is a large uncertainty
in model parameters. We demonstrate these advantages in the classical Lorenz-63
chaotic system and in networks of Hindmarsh-Rose neurons before application to
experimentally collected structured population data.
PMID- 28692643
TI - Inverse stochastic resonance in networks of spiking neurons.
AB - Inverse Stochastic Resonance (ISR) is a phenomenon in which the average spiking
rate of a neuron exhibits a minimum with respect to noise. ISR has been studied
in individual neurons, but here, we investigate ISR in scale-free networks, where
the average spiking rate is calculated over the neuronal population. We use
Hodgkin-Huxley model neurons with channel noise (i.e., stochastic gating variable
dynamics), and the network connectivity is implemented via electrical or chemical
connections (i.e., gap junctions or excitatory/inhibitory synapses). We find that
the emergence of ISR depends on the interplay between each neuron's intrinsic
dynamical structure, channel noise, and network inputs, where the latter in turn
depend on network structure parameters. We observe that with weak gap junction or
excitatory synaptic coupling, network heterogeneity and sparseness tend to favor
the emergence of ISR. With inhibitory coupling, ISR is quite robust. We also
identify dynamical mechanisms that underlie various features of this ISR
behavior. Our results suggest possible ways of experimentally observing ISR in
actual neuronal systems.
PMID- 28692644
TI - Correction: Accuracy Maximization Analysis for Sensory-Perceptual Tasks:
Computational Improvements, Filter Robustness, and Coding Advantages for Scaled
Additive Noise.
AB - [This corrects the article DOI: 10.1371/journal.pcbi.1005281.].
PMID- 28692645
TI - Benzodiazepine and Z-drug use and risk of pneumonia in patients with chronic
kidney disease: A population-based nested case-control study.
AB - BACKGROUND: Concerns were raised about pneumonia development from benzodiazepines
(BZDs) and Z-drugs, but direct evidence is limited, conflicting and without
examining the highly susceptible patients with chronic kidney disease (CKD) nor
specifying the risk for different drug utilizations. This study aimed to
investigate whether use of BZDs and Z-drugs was each associated with an increased
risk of pneumonia in a CKD population. METHODS: We performed a nested case
control study of 36,880 CKD patients analyzing the Taiwan National Health
Insurance Database between 01/1/2000 and 12/31/2011. Among the study cohort, we
identified 4,533 cases of pneumonia based on validated disease codes, chest x-ray
examination, and prescriptions of respiratory antibiotics, and randomly selected
16,388 controls from risk sets, matched by sex, age, and number of CKD-related
hospitalizations. All prescription filling records of BZDs and Z-drugs in the
year before the event/index date were analyzed for cases and controls.
Conditional logistic regressions were performed to estimate the odds ratios
(ORs). RESULTS: Current use of BZDs was associated with a 1.31-fold (95% CI, 1.18
1.26) increased risk of pneumonia compared to nonuse, but not for recent and past
use. The risk from current BZD use was confined to new initiation (adjusted OR,
2.47; 95% CI, 2.02-3.03) or use for <= 30 days, and elevated to 2.88-fold (95%
CI, 1.87-4.42) with parenteral administration. New initiation and current short
term use of Z-drugs was associated with a 2.94-fold (95% CI, 1.65-5.26) and 1.75
fold (95% CI, 1.13-2.72) increased risk of pneumonia, respectively. The findings
were robust to adoption of a case-crossover study that analyzed cases only.
CONCLUSIONS: Use of BZRAs is associated with an increased risk of pneumonia in
CKD patients, especially for patients newly initiating BZDs or Z-drugs or those
injected with BZDs. Physicians should exercise cautions for signs of pneumonia
when prescribing BZDs or Z-drugs to CKD patients.
PMID- 28692646
TI - Biomarkers for predicting type 2 diabetes development-Can metabolomics improve on
existing biomarkers?
AB - AIM: The aim was to determine if metabolomics could be used to build a predictive
model for type 2 diabetes (T2D) risk that would improve prediction of T2D over
current risk markers. METHODS: Gas chromatography-tandem mass spectrometry
metabolomics was used in a nested case-control study based on a screening sample
of 64-year-old Caucasian women (n = 629). Candidate metabolic markers of T2D were
identified in plasma obtained at baseline and the power to predict diabetes was
tested in 69 incident cases occurring during 5.5 years follow-up. The
metabolomics results were used as a standalone prediction model and in
combination with established T2D predictive biomarkers for building eight T2D
prediction models that were compared with each other based on their sensitivity
and selectivity for predicting T2D. RESULTS: Established markers of T2D (impaired
fasting glucose, impaired glucose tolerance, insulin resistance (HOMA), smoking,
serum adiponectin)) alone, and in combination with metabolomics had the largest
areas under the curve (AUC) (0.794 (95% confidence interval [0.738-0.850]) and
0.808 [0.749-0.867] respectively), with the standalone metabolomics model based
on nine fasting plasma markers having a lower predictive power (0.657 [0.577
0.736]). Prediction based on non-blood based measures was 0.638 [0.565-0.711]).
CONCLUSIONS: Established measures of T2D risk remain the best predictor of T2D
risk in this population. Additional markers detected using metabolomics are
likely related to these measures as they did not enhance the overall prediction
in a combined model.
PMID- 28692647
TI - The effects of kisspeptin-10 on serum metabolism and myocardium in rats.
AB - Kisspeptin is a peptide encoded by the Kiss 1 gene and is also called metastin.
Previous studies have generally focused on several functions of this peptide,
including metastasis, puberty, vasoconstriction and reproduction. However, few
studies have focused on the cardiac functions of kisspeptin. In the present
study, cardiac histomorphology was observed via TEM (transmission electron
microscope) and HE and Masson staining to observe instinctive changes. Serum
metabolites levels were also measured and analyzed using GC/TOF-MS after
injection with kisspeptin-10. A gene chip was employed to screen the potential
genes and pathways in the myocardium at the transcriptional leve, while RT-PCR
and Western Blot were conducted to verify the relevant mRNA and protein
expression, respectively. Histopathological findings demonstrated that there were
many irregular wavy contractions through HE staining and increased fibrosis
around the heart cells through Masson staining after treatment with kisspeptin
10. Additionally, the main changes in ultrastructure, including changes in
mitochondrial and broken mitochondrial cristae, could be observed with TEM after
treatment with kisspeptin-10. The PCA scores plot of the serum metabolites was in
the apparent partition after injection of kisspeptin-10. Twenty-six obviously
changed metabolites were detected and classified as amino acids, carbohydrate
metabolites, organic acids and other metabolites. Furthermore, gene chip analysis
showed 1112 differentially expressed genes after treatment with kisspeptin-10,
including 330 up-regulated genes and 782 down-regulated genes. These genes were
enriched in several signaling pathways related to heart diseases. The RT-PCR
result for ITGB8, ITGA4, ITGB7, MYL7, HIF1-alpha and BNP corresponded with the
gene chip assay. Moreover, the upregulated genes ITGB8, ITGA4 and BNP also
displayed consistent protein levels in Western Blot results. In summary, these
findings suggest that kisspeptin-10 could alter the morphology and structure of
myocardial cells, serum metabolite levels, and expression of genes and proteins
in heart tissues. Our work determined the profound effects of kisspeptin-10 on
the heart, which could further lead to the development of therapeutics related to
kisspeptin-10, including antagonists and analogs.
PMID- 28692648
TI - Zebrafish slc30a10 deficiency revealed a novel compensatory mechanism of Atp2c1
in maintaining manganese homeostasis.
AB - Recent studies found that mutations in the human SLC30A10 gene, which encodes a
manganese (Mn) efflux transporter, are associated with hypermanganesemia with
dystonia, polycythemia, and cirrhosis (HMDPC). However, the relationship between
Mn metabolism and HMDPC is poorly understood, and no specific treatments are
available for this disorder. Here, we generated two zebrafish slc30a10 mutant
lines using the CRISPR/Cas9 system. Compared to wild-type animals, mutant adult
animals developed significantly higher systemic Mn levels, and Mn accumulated in
the brain and liver of mutant embryos in response to exogenous Mn. Interestingly,
slc30a10 mutants developed neurological deficits in adulthood, as well as
environmental Mn-induced manganism in the embryonic stage; moreover, mutant
animals had impaired dopaminergic and GABAergic signaling. Finally, mutant
animals developed steatosis, liver fibrosis, and polycythemia accompanied by
increased epo expression. This phenotype was rescued partially by EDTA- CaNa2
chelation therapy and iron supplementation. Interestingly, prior to the onset of
slc30a10 expression, expressing ATP2C1 (ATPase secretory pathway Ca2+
transporting 1) protected mutant embryos from Mn exposure, suggesting a
compensatory role for Atp2c1 in the absence of Slc30a10. Notably, expressing
either wild-type or mutant forms of SLC30A10 was sufficient to inhibit the effect
of ATP2C1 in response to Mn challenge in both zebrafish embryos and HeLa cells.
These findings suggest that either activating ATP2C1 or restoring the Mn-induced
trafficking of ATP2C1 can reduce Mn accumulation, providing a possible target for
treating HMDPC.
PMID- 28692649
TI - Individual ball possession in soccer.
AB - This paper describes models for detecting individual and team ball possession in
soccer based on position data. The types of ball possession are classified as
Individual Ball Possession (IBC), Individual Ball Action (IBA), Individual Ball
Control (IBC), Team Ball Possession (TBP), Team Ball Control (TBC) und Team
Playmaking (TPM) according to different starting points and endpoints and the
type of ball control involved. The machine learning approach used is able to
determine how long the ball spends in the sphere of influence of a player based
on the distance between the players and the ball together with their direction of
motion, speed and the acceleration of the ball. The degree of ball control
exhibited during this phase is classified based on the spatio-temporal
configuration of the player controlling the ball, the ball itself and opposing
players using a Bayesian network. The evaluation and application of this approach
uses data from 60 matches in the German Bundesliga season of 2013/14, including
69,667 IBA intervals. The identification rate was F = .88 for IBA and F = .83 for
IBP, and the classification rate for IBC was kappa = .67. Match analysis showed
the following mean values per match: TBP 56:04 +/- 5:12 min, TPM 50:01 +/- 7:05
min and TBC 17:49 +/- 8:13 min. There were 836 +/- 424 IBC intervals per match
and their number was significantly reduced by -5.1% from the 1st to 2nd half. The
analysis of ball possession at the player level indicates shortest accumulated
IBC times for the central forwards (0:49 +/- 0:43 min) and the longest for
goalkeepers (1:38 +/- 0:58 min), central defenders (1:38 +/- 1:09 min) and
central midfielders (1:27 +/- 1:08 min). The results could improve performance
analysis in soccer, help to detect match events automatically, and allow
discernment of higher value tactical structures, which is based on individual
ball possession.
PMID- 28692650
TI - Expression, purification, and contaminant detection for structural studies of
Ralstonia metallidurance ClC protein rm1.
AB - Single-particle electron cryo-microscopy (cryo-EM) has become a popular method
for high-resolution study of the structural and functional properties of
proteins. However, sufficient expression and purification of membrane proteins
holds many challenges. We describe methods to overcome these obstacles using ClC
rm1, a prokaryotic chloride channel (ClC) family protein from Ralstonia
metallidurans, overexpressed in Escherichia coli (E. coli) BL21(DE3) strain. Mass
spectrometry and electron microscopy analyses of purified samples revealed
multiple contaminants that can obfuscate results of subsequent high-resolution
structural analysis. Here we describe the systematic optimization of sample
preparation procedures, including expression systems, solubilization techniques,
purification protocols, and contamination detection. We found that expressing ClC
rm1 in E. coli BL21(DE3) and using n-dodecyl-beta-D-maltopyranoside as a
detergent for solubilization and purification steps resulted in the highest
quality samples of those we tested. However, although protein yield, sample
stability, and the resolution of structural detail were improved following these
changes, we still detected contaminants including Acriflavine resistant protein
AcrB. AcrB was particularly difficult to remove as it co-purified with ClC-rm1
due to four intrinsic histidine residues at its C-terminus that bind to affinity
resins. We were able to obtain properly folded pure ClC-rm1 by adding eGFP to the
C-terminus and overexpressing the protein in the DeltaacrB variant of the JW0451
2 E. coli strain.
PMID- 28692651
TI - Effects of clinical and environmental factors on bronchoalveolar antibody
responses to Pneumocystis jirovecii: A prospective cohort study of HIV+ patients.
AB - BACKGROUND: Humoral immunity plays an important role against Pneumocystis
jirovecii infection, yet clinical and environmental factors that impact
bronchoalveolar antibody responses to P. jirovecii remain uncertain. METHODS:
From October 2008-December 2011 we enrolled consecutive HIV-infected adults
admitted to San Francisco General Hospital (SFGH) who underwent bronchoscopy for
suspected Pneumocystis pneumonia (PCP). We used local air quality monitoring data
to assign ozone, nitrogen dioxide, and fine particulate matter exposures within
14 days prior to hospital admission. We quantified serum and bronchoalveolar
lavage fluid (BALF) antibody responses to P. jirovecii major surface glycoprotein
(Msg) recombinant constructs using ELISA. We then fit linear regression models to
determine whether PCP and ambient air pollutants were associated with
bronchoalveolar antibody responses to Msg. RESULTS: Of 81 HIV-infected patients
enrolled, 47 (58%) were diagnosed with current PCP and 9 (11%) had a prior
history of PCP. The median CD4+ count was 51 cells/MUl (IQR 15-129) and 44% were
current smokers. Serum antibody responses to Msg were statistically significantly
predictive of BALF antibody responses, with the exception of IgG responses to
MsgC8 and MsgC9. Prior PCP was associated with increased BALF IgA responses to
Msg and current PCP was associated with decreased IgA responses. For instance,
among patients without current PCP, those with prior PCP had a median 73.2 U (IQR
19.2-169) IgA response to MsgC1 compared to a 5.00 U (3.52-12.6) response among
those without prior PCP. Additionally, current PCP predicted a 22.5 U (95%CI
39.2, -5.82) lower IgA response to MsgC1. Ambient ozone within the two weeks
prior to hospital admission was associated with decreased BALF IgA responses to
Msg while nitrogen dioxide was associated with increased IgA responses.
CONCLUSIONS: PCP and ambient air pollutants were associated with BALF IgA
responses to P. jirovecii in HIV-infected patients evaluated for suspected PCP.
PMID- 28692652
TI - Developmental transcriptomic analyses for mechanistic insights into critical
pathways involved in embryogenesis of pelagic mahi-mahi (Coryphaena hippurus).
AB - Mahi-mahi (Coryphaena hippurus) is a commercially and ecologically important
species of fish occurring in tropical and temperate waters worldwide.
Understanding early life events is crucial for predicting effects of
environmental stress, which is largely restricted by a lack of genetic resources
regarding expression of early developmental genes and regulation of pathways. The
need for anchoring developmental stages to transcriptional activities is
highlighted by increasing evidence on the impacts of recurrent worldwide oil
spills in this sensitive species during early development. By means of high
throughput sequencing, we characterized the developmental transcriptome of mahi
mahi at three critical developmental stages, from pharyngula embryonic stage (24
hpf) to 48 hpf yolk-sac larva (transition 1), and to 96 hpf free-swimming larva
(transition 2). With comparative analysis by multiple bioinformatic tools, a
larger number of significantly altered genes and more diverse gene ontology terms
were observed during transition 2 than transition 1. Cellular and tissue
development terms were more significantly enriched in transition 1, while
metabolism related terms were more enriched in transition 2, indicating a switch
progressing from general embryonic development to metabolism during the two
transitions. Special focus was given on the most significant common canonical
pathways (e.g. calcium signaling, glutamate receptor signaling, cAMP response
element-binding protein signaling, cardiac beta-adrenergic signaling, etc.) and
expression of developmental genes (e.g. collagens, myosin, notch, glutamate
metabotropic receptor etc.), which were associated with morphological changes of
nervous, muscular, and cardiovascular system. These data will provide an
important basis for understanding embryonic development and identifying molecular
mechanisms of abnormal development in fish species.
PMID- 28692653
TI - Social exclusion and psychopathology in an online cohort of Moroccan-Dutch
migrants: Results of the MEDINA-study.
AB - INTRODUCTION: Migration is seen as a risk factor for developing psychiatric
symptoms and experiencing social exclusion. In the Netherlands, the Moroccan
Dutch population is the second largest migrant group. 70% of all young Moroccan
Dutch people meet each other in the online community www.marokko.nl. Within this
community, we investigated the association between experiences of social
exclusion and self-reported depressive symptoms and psychotic experiences.
MATERIALS AND METHODS: Participants were recruited via the website
www.marokko.nl. They completed an online survey, with screening instruments for
depressive symptoms (K10) and psychotic experiences (PQ-16), measures of social
exclusion (perceived discrimination, social defeat and social support), and
questions about demographical information. With regression analysis the
association between social exclusion and psychiatric symptoms was investigated.
RESULTS: We included 267 participants; 87% were female. 27% of the sample has
received mental healthcare in the past. Over 50% of these people screened
positive for depressive symptoms and psychotic experiences. Perceived
discrimination and social defeat were significantly associated with psychotic
experiences and social defeat was associated with depressive symptoms. Social
support and higher education were associated with less depressive symptoms and
psychotic experiences. DISCUSSION: Our findings suggest that the online
environment allows for epidemiological research and early symptom detection.
Levels of psychopathology were high in our sample. This suggests that a part of
this young ethnic minority population might not get adequate mental healthcare.
Since this population can be reached through Internet, the online environment may
therefore also offer an appropriate setting for intervention, to increase
resilience towards social exclusion.
PMID- 28692654
TI - Estimating the basic reproduction rate of HFMD using the time series SIR model in
Guangdong, China.
AB - Hand, foot, and mouth disease (HFMD) has caused a substantial burden of disease
in China, especially in Guangdong Province. Based on notifiable cases, we use the
time series Susceptible-Infected-Recovered model to estimate the basic
reproduction rate (R0) and the herd immunity threshold, understanding the
transmission and persistence of HFMD more completely for efficient intervention
in this province. The standardized difference between the reported and fitted
time series of HFMD was 0.009 (<0.2). The median basic reproduction rate of
total, enterovirus 71, and coxsackievirus 16 cases in Guangdong were 4.621 (IQR:
3.907-5.823), 3.023 (IQR: 2.289-4.292) and 7.767 (IQR: 6.903-10.353),
respectively. The heatmap of R0 showed semiannual peaks of activity, including a
major peak in spring and early summer (about the 12th week) followed by a smaller
peak in autumn (about the 36th week). The county-level model showed that
Longchuan (R0 = 33), Gaozhou (R0 = 24), Huazhou (R0 = 23) and Qingxin (R0 = 19)
counties have higher basic reproduction rate than other counties in the province.
The epidemic of HFMD in Guangdong Province is still grim, and strategies like the
World Health Organization's expanded program on immunization need to be
implemented. An elimination of HFMD in Guangdong might need a Herd Immunity
Threshold of 78%.
PMID- 28692655
TI - Population-based incidence, seasonality and serotype distribution of invasive
salmonellosis among children in Nanoro, rural Burkina Faso.
AB - BACKGROUND: Bloodstream infections (BSI) caused by Salmonella Typhi and invasive
non-Typhoidal Salmonella (iNTS) frequently affect children living in rural sub
Saharan Africa but data about incidence and serotype distribution are rare.
OBJECTIVE: The present study assessed the population-based incidence of
Salmonella BSI and severe malaria in a Health and Demographic Surveillance System
in a rural area with seasonal malaria transmission in Nanoro, Burkina Faso.
METHODS: Children between 2 months-15 years old with severe febrile illness were
enrolled during a one-year surveillance period (May 2013-May 2014). Thick blood
films and blood cultures were sampled and processed upon admission. Population
based incidences were corrected for non-referral, health seeking behavior, non
inclusion and blood culture sensitivity. Adjusted incidence rates were expressed
per 100,000 person-years of observations (PYO). RESULTS: Among children < 5 years
old, incidence rates for iNTS, Salmonella Typhi and severe malaria per 100,000
PYO were 4,138 (95% Confidence Interval (CI): 3,740-4,572), 224 (95% CI: 138-340)
and 2,866 (95% CI: 2,538-3,233) respectively. Among those aged 5-15 years,
corresponding incidence rates were 25 (95% CI: 8-60), 273 (95% CI: 203-355) and
135 (95% CI: 87-195) respectively. Most iNTS occurred during the peak of the
rainy season and in parallel with the increase of Plasmodium falciparum malaria;
for Salmonella Typhi no clear seasonal pattern was observed. Salmonella Typhi and
iNTS accounted for 13.3% and 55.8% of all 118 BSI episodes; 71.6% of iNTS (48/67)
isolates were Salmonella enterica serovar Typhimurium and 25.4% (17/67)
Salmonella enterica serovar Enteritidis; there was no apparent geographical
clustering. CONCLUSION: The present findings from rural West-Africa confirm high
incidences of Salmonella Typhi and iNTS, the latter with a seasonal and
Plasmodium falciparum-related pattern. It urges prioritization of the development
and implementation of Salmonella Typhi as well as iNTS vaccines in this setting.
PMID- 28692656
TI - Growth performance and development of internal organ, and gastrointestinal tract
of calf supplementation with calcium propionate at various stages of growth
period.
AB - To investigate the effects of calcium propionate (CaP) supplementation on
performance, the development of the internal organ, and gastrointestinal tract of
calves at various stages of growth period, 54 male Jersey calves (age = 7 +/- 1
d, body weight(BW) = 23.1 +/- 1.2 kg) were randomly allocated to three treatment
groups. While control calves were fed basis dietary with no additives (0CaP),
other treatment calves were fed basis dietary supplementation with CaP at 50
(5CaP) or 100 (10CaP) g kg-1 dry matter. The experiment lasted 160 d and was
divided into three feeding stages: Stage 1 (d 0 to 30), Stage 2 (d 31 to 90), and
Stage 3 (d 91 to160). Six calves from each group were randomly selected and
slaughtered on days 30, 90, and 160 when at the conclusion of each experimental
feeding stage. The BW of calves increased with 10CaP after feeding 90 d, whereas
it increased with 5CaP and 10CaP at feeding 120d and 160d compared to 0CaP. The
10CaP group improved average daily gain (ADG) of calves at stage 2, and d120-160
of stage 3 compared with the 0CaP group. The ADG of 5CaP was greater than the
0CaP group only at 120-160 d of stage 3 compared with the 0CaP group. The results
of feed efficiency were in agreed with ADG as no dry matter intake difference at
all stages of growth period. The 10CaP treatment exhibited the greatest spleen
weight among the treatment at the end of the experiment; the liver weight of the
5CaP and 10CaP calves at feeding 90 d and of the 10CaP calves at feeding 160 d
and were greater than those of the 0CaP animals. The CaP at the tested doses
increased the rumen weight after feeding 90d of Jersey calves, and also improved
the development of intestine. In conclusion, dietary supplementation with calcium
propionate at the tested doses caused a beneficial effect in the growth
performance and gastrointestinal tract traits of Jersey calves, thus to add 10%
CaP before feeding 90 days was better and 5% CaP supplementation was expected at
the period for feeding 90 to160 d.
PMID- 28692657
TI - Improper wound treatment and delay of rabies post-exposure prophylaxis of animal
bite victims in China: Prevalence and determinants.
AB - BACKGROUND: Rabies is invariably a fatal disease. Appropriate wound treatment and
prompt rabies post-exposure prophylaxis (PEP) are of great importance to rabies
prevention. The objective of this study was to investigate the prevalence and
influencing factors of improper wound treatment and delay of rabies PEP after an
animal bite in Wuhan, China. METHODOLOGY: This cross-sectional study was
conducted among animal bite victims visiting rabies prevention clinics (RPCs). We
selected respondents by a multistage sampling technique. A face-to-face interview
was conducted to investigate whether the wound was treated properly and the time
disparity between injury and attendance to the RPCs. Determinants of improper
wound treatment and delay of rabies PEP were identified by a stepwise
multivariate logistic regression analysis. PRINCIPAL FINDINGS: In total, 1,015
animal bite victims (564 women and 451 men) responded to the questionnaire, and
the response rate was 93.98%. Overall, 81.2% of animal bite victims treated their
wounds improperly after suspected rabies exposure, and 35.3% of animal bite
victims delayed the initiation of PEP. Males (OR = 1.871, 95% CI: 1.318-2.656),
residents without college education (OR = 1.698, 95% CI: 1.203-2.396),
participants liking to play with animals (OR = 1.554, 95% CI: 1.089-2.216), and
people who knew the fatality of rabies (OR = 1.577, 95% CI: 1.096-2.270), were
more likely to treat wounds improperly after an animal bite. Patients aged 15-44
years (OR = 2.324, 95% CI: 1.457-3.707), who were bitten or scratched by a
domestic animal (OR = 1.696, 95% CI: 1.103-2.608) and people who knew the
incubation period of rabies (OR = 1.844, 95% CI: 1.279-2.659) were inclined to
delay the initiation of PEP. CONCLUSIONS: Our investigation shows that improper
wound treatment and delayed PEP is common among animal bite victims, although
RPCs is in close proximity and PEP is affordable. The lack of knowledge and poor
awareness might be the main reason for improper PEP. Educational programs and
awareness raising campaigns should be a priority to prevent rabies, especially
targeting males, the less educated and those aged 15-44 years.
PMID- 28692658
TI - Temporal specificity of the initial adaptive response in motor adaptation.
AB - Repeated exposure to a novel physical environment eventually leads to a mature
adaptive response whereby feedforward changes in motor output mirror both the
amplitude and temporal structure of the environmental perturbations. However,
adaptive responses at the earliest stages of learning have been found to be not
only smaller, but systematically less specific in their temporal structure
compared to later stages of learning. This observation has spawned a lively
debate as to whether the temporal structure of the initial adaptive response is,
in fact, stereotyped and non-specific. To settle this debate, we directly
measured the adaptive responses to velocity-dependent and position-dependent
force-field perturbations (vFFs and pFFs) at the earliest possible stage of motor
learning in humans-after just a single-movement exposure. In line with previous
work, we found these earliest stage adaptive responses to be more similar than
the perturbations that induced them. However, the single-trial adaptive responses
for vFF and pFF perturbations were clearly distinct, and the disparity between
them reflected the difference between the temporal structure of the perturbations
that drove them. Critically, we observed these differences between single-trial
adaptive responses when vFF and pFF perturbations were randomly intermingled from
one trial to the next within the same block, indicating perturbation response
specificity at the single trial level. These findings demonstrate that the
initial adaptive responses to physical perturbations are not stereotyped.
Instead, the neural plasticity in sensorimotor areas is sensitive to the temporal
structure of a movement perturbation even at the earliest stage in learning. This
insight has direct implications for the development of computational models of
early-stage motor adaptation and the evolution of this adaptive response with
continued training.
PMID- 28692659
TI - Lesbian, gay, bisexual, and transgender (LGBT) health services in the United
States: Origins, evolution, and contemporary landscape.
AB - BACKGROUND: LGBT community organizations in the United States have been providing
health services since at least the 1970s. However, available explanations for the
origins of LGBT health services do not sufficiently explain why health in
particular has been so closely and consistently linked to LGBT activism. Little
is also known regarding how LGBT health services may have evolved over time with
the growing scientific understanding of LGBT health needs. METHODS: This study
begins with a review of the early intersections of sexuality and health that led
to an LGBT health movement in the United States, as well as the evolution of LGBT
health services over time. Informed by this, an asset map displaying the location
and types of services provided by "LGBT community health centers" today in
relation to the population density of LGBT people was explored. An online search
of LGBT community health centers was conducted between September-December, 2015.
Organizational details, including physical addresses and the services provided,
were confirmed via an online database of federally-registered non-profit
organizations and organizational websites. The locations and types of services
provided were analyzed and presented alongside county-level census data of same
sex households using geographic information system (GIS) software ArcGIS for
Desktop. FINDINGS: LGBT community health centers are concentrated within urban
hubs and coastal states, and are more likely to be present in areas with a high
density of same-sex couples. LGBT community health centers do not operate in 13
states. The most common health services provided are wellness programs, HIV/STI
services, and counseling services. CONCLUSIONS: LGBT community health centers
have adapted over time to meet the needs of LGBT people. However, significant
gaps in service remain in the United States, and LGBT community health centers
may require significant transformations going forward in order to continue
serving LGBT people.
PMID- 28692660
TI - N-(3-oxododecanoyl)-L-homoserine lactone interactions in the breast tumor
microenvironment: Implications for breast cancer viability and proliferation in
vitro.
AB - It is well documented that the tumor microenvironment profoundly impacts the
etiology and progression of breast cancer, yet the contribution of the resident
microbiome within breast tissue remains poorly understood. Tumor
microenvironmental conditions, such as hypoxia and dense tumor stroma, predispose
progressive phenotypes and therapy resistance, however the role of bacteria in
this interplay remains uncharacterized. We hypothesized that the effect of
individual bacterial secreted molecules on breast cancer viability and
proliferation would be modulated by these tumor-relevant stressors differentially
for cells at varying stages of progression. To test this, we incubated human
breast adenocarcinoma cells (MDA-MB-231, MCF-DCIS.com) and non-malignant breast
epithelial cells (MCF-10A) with N-(3-oxododecanoyl)-L-homoserine lactone (OdDHL),
a quorum-sensing molecule from Pseudomonas aeruginosa that regulates bacterial
stress responses. This molecule was selected because Pseudomonas was recently
characterized as a significant fraction of the breast tissue microbiome and OdDHL
is documented to impact mammalian cell viability. After OdDHL treatment, we
demonstrated the greatest decrease in viability with the more malignant MDA-MB
231 cells and an intermediate MCF-DCIS.com (ductal carcinoma in situ) response.
The responses were also culture condition (i.e. microenvironment) dependent.
These results contrast the MCF-10A response, which demonstrated no change in
viability in any culture condition. We further determined that the observed
trends in breast cancer viability were due to modulation of proliferation for
both cell types, as well as the induction of necrosis for MDA-MB-231 cells in all
conditions. Our results provide evidence that bacterial quorum-sensing molecules
interact with the host tissue environment to modulate breast cancer viability and
proliferation, and that the effect of OdDHL is dependent on both cell type as
well as microenvironment. Understanding the interactions between bacterial
signaling molecules and the host tissue environment will allow for future studies
that determine the contribution of bacteria to the onset, progression, and
therapy response of breast cancer.
PMID- 28692661
TI - The extracellular matrix and focal adhesion kinase signaling regulate cancer stem
cell function in pancreatic ductal adenocarcinoma.
AB - Cancer stem cells (CSCs) play an important role in the clonogenic growth and
metastasis of pancreatic ductal adenocarcinoma (PDAC). A hallmark of PDAC is the
desmoplastic reaction, but the impact of the tumor microenvironment (TME) on CSCs
is unknown. In order to better understand the mechanisms, we examined the impact
of extracellular matrix (ECM) proteins on PDAC CSCs. We quantified the effect of
ECM proteins, beta1-integrin, and focal adhesion kinase (FAK) on clonogenic PDAC
growth and migration in vitro and tumor initiation, growth, and metastasis in
vivo in nude mice using shRNA and overexpression constructs as well as small
molecule FAK inhibitors. Type I collagen increased PDAC tumor initiating
potential, self-renewal, and the frequency of CSCs through the activation of FAK.
FAK overexpression increased tumor initiation, whereas a dominant negative FAK
mutant or FAK kinase inhibitors reduced clonogenic PDAC growth in vitro and in
vivo. Moreover, the FAK inhibitor VS-4718 extended the anti-tumor response to
gemcitabine and nab-paclitaxel in patient-derived PDAC xenografts, and the loss
of FAK expression limited metastatic dissemination of orthotopic xenografts. Type
I collagen enhances PDAC CSCs, and both kinase-dependent and independent
activities of FAK impact PDAC tumor initiation, self-renewal, and metastasis. The
anti-tumor impact of FAK inhibitors in combination with standard chemotherapy
support the clinical testing of this combination.
PMID- 28692662
TI - Potential malignant transformation in the gastric mucosa of immunodeficient mice
with persistent Mycoplasma penetrans infection.
AB - Mycoplasma infection has been reported in immunocompromised cancer patients;
nevertheless, it is not clear if persistent Mycoplasma infection could facilitate
the proliferation of cancer cells in immunocompromised organisms. The aim of this
study was to examine the relationship between persistent Mycoplasma infection and
malignant transformation in an immunodeficient host model. Immunodeficient mouse
model was established using cyclophosphamide and mice gastric mucosal cells were
infected with Mycoplasma penetrans (Mpe). After 18 weeks, mice were sacrificed
and gastric mucosal Mpe infected cells were identified by fluorescence in situ
hybridization (FISH). Moreover, pathological and ultrastructural changes in mice
gastric mucosa were evaluated and the expression of multiple proto-oncogenes was
examined by Western blot. Our data show that Mpe infection was detected in the
blood of immunodeficient mice and Mpe persistent infection in mice gastric mucosa
was confirmed by FISH. There were pathological and ultrastructural malignant
transformation occurred in the gastric mucosa of infected mice compared to
control mice. Mpe infected mice showed lower expression of p53 and p21 and higher
H-ras expression compared to the control group. Moreover, expression of NF-kappaB
p65 subunit increased in Mpe infected mice, similar to the TNF-alpha expression.
Bax expression in gastric mucosa of Mpe infected mice was lower while Bcl-2
expression was higher than in the uninfected control group. Collectively these
data demonstrate that persistent Mpe infection is associated with aberrant
expression of multiple proto-oncogenes in gastric mucosa of immunodeficient mice
which potentially facilitate the malignant transformation.
PMID- 28692663
TI - Cancer trials in sub-Saharan Africa: Aligning research and care.
AB - Satish Gopal discusses the challenges of deliverable cancer care and cancer
trials in sub-Saharan Africa as well as a potential framework for overcoming
these challenges.
PMID- 28692664
TI - A functional approach to understanding the role of NCKX5 in Xenopus pigmentation.
AB - NCKX5 is an ion exchanger expressed mostly in pigment cells; however, the
functional role for this protein in melanogenesis is not clear. A variant allele
of SLC24A5, the gene encoding NCKX5, has been shown to correlate with lighter
skin pigmentation in humans, indicating a key role for SLC24A5 in determining
human skin colour. SLC24A5 expression has been found to be elevated in melanoma.
Knockdown analyses have shown SLC24A5 to be important for pigmentation, but to
date the function of this ion exchanger in melanogenesis has not been fully
established. Our data suggest NCKX5 may have an alternative activity that is key
to its role in the regulation of pigmentation. Here Xenopus laevis is employed as
an in vivo model system to further investigate the function of NCKX5 in
pigmentation. SLC24A5 is expressed in the melanophores as they differentiate from
the neural crest and develop in the RPE of the eye. Morpholino knockdown and
rescue experiments were designed to elucidate key residues and regions of the
NCKX5 protein. Unilateral morpholino injection at the 2 cell stage resulted in a
reduction of pigmentation in the eye and epidermis of one lateral side of the
tadpole. Xenopus and human SLC24A5 can rescue the morpholino effects. Further
rescue experiments including the use of ion exchange inactive SLC24A5 constructs
raise the possibility that full ion exchanger function of NCKX5 may not be
required for rescue of pigmentation.
PMID- 28692665
TI - Brackish habitat dictates cultivable Actinobacterial diversity from marine
sponges.
AB - Bacterial communities associated with marine invertebrates such as sponges and
ascidians have demonstrated potential as sources of bio-medically relevant small
molecules. Metagenomic analysis has shown that many of these invertebrates harbor
populations of Actinobacteria, many of which are cultivable. While some
populations within invertebrates are transmitted vertically, others are obtained
from the environment. We hypothesized that cultivable diversity from sponges
living in brackish mangrove habitats have associations with Actinobacterial
populations that differ from those found in clear tropical waters. In this study,
we analyzed the cultivable Actinobacterial populations from sponges found in
these two distinct habitats with the aim of understanding the secondary
metabolite potential. Importantly, we wanted to broadly evaluate the potential
differences among these groups to guide future Actinobacterial collection
strategies for the purposes of drug discovery.
PMID- 28692666
TI - On the core bacterial flora of Ixodes persulcatus (Taiga tick).
AB - Ixodes persulcatus is a predominant hard tick species that transmits a wide range
of human and animal pathogens. Since bacterial flora of the tick dwelling in the
wild always vary according to their hosts and the environment, it is highly
desirable that species-associated microbiomes are fully determined by using next
generation sequencing and based on comparative metagenomics. Here, we examine
such metagenomic changes of I. persulcatus starting with samples collected from
the wild ticks and followed by the reared animals under pathogen-free laboratory
conditions over multiple generations. Based on high-coverage genomic sequences
from three experimental groups-wild, reared for a single generation or R1, and
reared for eight generations or R8 -we identify the core bacterial flora of I.
persulcatus, which contains 70 species that belong to 69 genera of 8 phyla; such
a core is from the R8 group, which is reduced from 4625 species belonging to 1153
genera of 29 phyla in the wild group. Our study provides a novel example of tick
core bacterial flora acquired based on wild-to-reared comparison, which paves a
way for future research on tick metagenomics and tick-borne disease pandemics.
PMID- 28692667
TI - Optimal Weights Mixed Filter for removing mixture of Gaussian and impulse noises.
AB - In this paper we consider the problem of restoration of a image contaminated by a
mixture of Gaussian and impulse noises. We propose a new statistic called ROADGI
which improves the well-known Rank-Ordered Absolute Differences (ROAD) statistic
for detecting points contaminated with the impulse noise in this context.
Combining ROADGI statistic with the method of weights optimization we obtain a
new algorithm called Optimal Weights Mixed Filter (OWMF) to deal with the mixed
noise. Our simulation results show that the proposed filter is effective for
mixed noises, as well as for single impulse noise and for single Gaussian noise.
PMID- 28692668
TI - A novel, species-specific, real-time PCR assay for the detection of the emerging
zoonotic parasite Ancylostoma ceylanicum in human stool.
AB - BACKGROUND: Molecular-based surveys have indicated that Ancylostoma ceylanicum, a
zoonotic hookworm, is likely the second most prevalent hookworm species infecting
humans in Asia. Most current PCR-based diagnostic options for the detection of
Ancylostoma species target the Internal Transcribed Spacer (ITS) regions of the
ribosomal gene cluster. These regions possess a considerable degree of
conservation among the species of this genus and this conservation can lead to
the misidentification of infecting species or require additional labor for
accurate species-level determination. We have developed a novel, real-time PCR
based assay for the sensitive and species-specific detection of A. ceylanicum
that targets a non-coding, highly repetitive genomic DNA element. Comparative
testing of this PCR assay with an assay that targets ITS sequences was conducted
on field-collected samples from Argentina and Timor-Leste to provide further
evidence of the sensitivity and species-specificity of this assay.
METHODS/PRINCIPAL FINDINGS: A previously described platform for the design of
primers/probe targeting non-coding highly repetitive regions was used for the
development of this novel assay. The assay's limits of detection (sensitivity)
and cross-reactivity with other soil-transmitted helminth species (specificity)
were assessed with real-time PCR experiments. The assay was successfully used to
identify infections caused by A. ceylanicum that were previously only identified
to the genus level as Ancylostoma spp. when analyzed using other published primer
probe pairings. Further proof of sensitive, species-specific detection was
provided using a published, semi-nested restriction fragment length polymorphism
PCR assay that differentiates between Ancylostoma species.
CONCLUSIONS/SIGNIFICANCE: Due to the close proximity of people and domestic/wild
animals in many regions of the world, the potential for zoonotic infections is
substantial. Sensitive tools enabling the screening for different soil
transmitted helminth infections are essential to the success of mass deworming
efforts and facilitate the appropriate interpretation of data. This study
describes a novel, species-specific, real-time PCR-based assay for the detection
of A. ceylanicum that will help to address the need for such tools in integrated
STH deworming programs. TRIAL REGISTRATION: ANZCTR.org.au ACTRN12614000680662.
PMID- 28692669
TI - Systems biology of the modified branched Entner-Doudoroff pathway in Sulfolobus
solfataricus.
AB - Sulfolobus solfataricus is a thermoacidophilic Archaeon that thrives in
terrestrial hot springs (solfatares) with optimal growth at 80 degrees C and pH 2
4. It catabolizes specific carbon sources, such as D-glucose, to pyruvate via the
modified Entner-Doudoroff (ED) pathway. This pathway has two parallel branches,
the semi-phosphorylative and the non-phosphorylative. However, the strategy of
S.solfataricus to endure in such an extreme environment in terms of robustness
and adaptation is not yet completely understood. Here, we present the first
dynamic mathematical model of the ED pathway parameterized with quantitative
experimental data. These data consist of enzyme activities of the branched
pathway at 70 degrees C and 80 degrees C and of metabolomics data at the same
temperatures for the wild type and for a metabolic engineered knockout of the
semi-phosphorylative branch. We use the validated model to address two questions:
1. Is this system more robust to perturbations at its optimal growth temperature?
2. Is the ED robust to deletion and perturbations? We employed a systems biology
approach to answer these questions and to gain further knowledge on the emergent
properties of this biological system. Specifically, we applied deterministic and
stochastic approaches to study the sensitivity and robustness of the system,
respectively. The mathematical model we present here, shows that: 1. Steady state
metabolite concentrations of the ED pathway are consistently more robust to
stochastic internal perturbations at 80 degrees C than at 70 degrees C; 2. These
metabolite concentrations are highly robust when faced with the knockout of
either branch. Connected with this observation, these two branches show different
properties at the level of metabolite production and flux control. These new
results reveal how enzyme kinetics and metabolomics synergizes with mathematical
modelling to unveil new systemic properties of the ED pathway in S.solfataricus
in terms of its adaptation and robustness.
PMID- 28692670
TI - Patient-reported outcomes and survival in multiple sclerosis: A 10-year
retrospective cohort study using the Multiple Sclerosis Impact Scale-29.
AB - BACKGROUND: There is increasing emphasis on using patient-reported outcomes
(PROs) to complement traditional clinical outcomes in medical research, including
in multiple sclerosis (MS). Research, particularly in oncology and heart failure,
has shown that PROs can be prognostic of hard clinical endpoints such as survival
time (time from study entry until death). However, unlike in oncology or
cardiology, it is unknown whether PROs are associated with survival time in
neurological diseases. The Multiple Sclerosis Impact Scale-29 (MSIS-29) is a PRO
sensitive to short-term change in MS, with questions covering both physical and
psychological quality of life. This study aimed to investigate whether MSIS-29
scores can be prognostic for survival time in MS, using a large observational
cohort of people with MS. METHODS AND FINDINGS: From 15 July 2004 onwards, MSIS
29 questionnaires were completed by people with MS registered with the MS Society
Tissue Bank (n = 2,126, repeated 1 year later with n = 872 of the original
respondents). By 2014, 264 participants (12.4%) had died. Higher baseline MSIS-29
physical (MSIS-29-PHYS) score was associated with reduced survival time (subgroup
with highest scores versus subgroup with lowest scores: hazard ratio [HR] 5.7,
95% CI 3.1-10.5, p < 0.001). Higher baseline MSIS-29 psychological score was also
associated with reduced survival time (subgroup with highest scores versus
subgroup with lowest scores: HR 2.8, 95% CI 1.8-4.4, p < 0.001). In those with
high baseline MSIS-29 scores, mortality risk was even greater if the MSIS-29
score worsened over 1 year (HR 2.3, 95% CI 1.2-4.4, p = 0.02). MSIS-29-PHYS
scores were associated with survival time independent of age, sex, and patient
reported Expanded Disability Status Scale score in a Cox regression analysis (per
1-SD increase in MSIS-29-PHYS score: HR 1.8, 95% CI 1.1-2.9, p = 0.03). A
limitation of the study is that this cohort had high baseline age and disability
levels; the prognostic value of MSIS-29 for survival time at earlier disease
stages requires further investigation. CONCLUSIONS: This study reports that PROs
can be prognostic for hard clinical outcomes in neurological disease, and
supports PROs as a meaningful clinical outcome for use in research and clinical
settings.
PMID- 28692671
TI - Immune profiles and clinical outcomes between sepsis patients with or without
active cancer requiring admission to intensive care units.
AB - BACKGROUND: Immunoparalysis was observed in both patients with cancer and sepsis.
In cancer patients, Cytotoxic T lymphocyte antigen-4 and programmed cell death
protein 1/programmed death-ligand 1 axis are two key components of
immunoparalysis. Several emerging therapies against these two axes gained
significant clinical benefit. In severe sepsis patients, immunoparalysis was
known as compensatory anti-inflammatory response syndrome and this has been
suggested as an important cause of death in patients with sepsis. It would be
interesting to see if immune status was different in severe sepsis patients with
or without active cancer. The aim of this study was to assess the differences in
immune profiles, and clinical outcomes between severe sepsis patients with or
without cancer admitted to ICU. METHODS: A combined retrospective and prospective
observational study from a cohort of adult sepsis patients admitted to three
medical ICUs at Kaohsiung Chang Gung Memorial Hospital in Taiwan between August
2013 and June 2016. RESULTS: Of the 2744 patients admitted to the ICU, 532
patients with sepsis were included. Patients were divided into those with or
without active cancer according to their medical history. Of the 532 patients, 95
(17.9%) patients had active cancer, and 437 (82.1%) patients had no active cancer
history. Patients with active cancer were younger (p = 0.001) and were less
likely to have diabetes mellitus (p < 0.001), hypertension (p < 0.001), coronary
artery disease (p = 0.004), chronic obstructive pulmonary disease (p = 0.002) or
stroke (p = 0.002) compared to patients without active cancer. Patients with
active cancer also exhibited higher baseline lactate levels (p = 0.038), and
higher baseline plasma interleukin (IL)-10 levels (p = 0.040), higher trend of
granulocyte colony-stimulating factor (G-CSF) (p = 0.004) compared to patients
without active cancer. The 14-day, 28-day and 90-day mortality rates were higher
for patients with active cancer than those without active cancer (P < 0.001 for
all intervals). CONCLUSIONS: Among patients admitted to the ICU with sepsis,
those with underling active cancer had higher baseline levels of plasma IL-10,
higher trend of G-CSF and higher mortality rate than those without active cancer.
PMID- 28692672
TI - The short chain fatty acid receptor GPR43 regulates inflammatory signals in
adipose tissue M2-type macrophages.
AB - The regulation of inflammatory responses within adipose tissue by various types
of immune cells is closely related to tissue homeostasis and progression of
metabolic disorders such as obesity and type 2 diabetes. G-protein-coupled
receptor 43 (GPR43), which is activated by short-chain fatty acids (SCFAs), is
known to be most abundantly expressed in white adipose tissue and to modulate
metabolic processes. Although GPR43 is also expressed in a wide variety of immune
cells, whether and how GPR43 in adipose tissue immune cells regulates the
inflammatory responses and metabolic homeostasis remains unknown. In this study,
we investigated the role of GPR43 in adipose tissue macrophages by using Gpr43
deficient mice and transgenic mice with adipose-tissue-specific overexpression of
GPR43. We found that GPR43 activation by SCFA resulted in induction of the pro
inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) in anti
inflammatory M2-type macrophages within adipose tissue. By contrast, this effect
was not noted in inflammatory M1-type macrophages, suggesting that GPR43 plays
distinct functions depending on macrophage types. Local TNF-alpha signaling
derived from steady-state adipose tissue is associated with proper tissue
remodeling as well as suppression of fat accumulation. Thus, GPR43-involving
mechanism that we have identified supports maintenance of adipose tissue
homeostasis and increase in metabolic activity. This newly identified facet of
GPR43 in macrophages may have clinical implications for immune-metabolism related
episodes.
PMID- 28692673
TI - Gastrointestinal parasite infections and self-medication in wild chimpanzees
surviving in degraded forest fragments within an agricultural landscape mosaic in
Uganda.
AB - Monitoring health in wild great apes is integral to their conservation and is
especially important where they share habitats with humans, given the potential
for zoonotic pathogen exchange. We studied the intestinal parasites of wild
chimpanzees (Pan troglodytes schweinfurthii) inhabiting degraded forest fragments
amid farmland and villages in Bulindi, Uganda. We first identified protozoan and
helminth parasites infecting this population. Sixteen taxa were demonstrated
microscopically (9 protozoa, 5 nematodes, 1 cestode, and 1 trematode). DNA
sequence analysis enabled more precise identification of larval nematodes (e.g.
Oesophagostomum stephanostomum, O. bifurcum, Strongyloides fuelleborni, Necator
sp. Type II) and tapeworm proglottids (genus Bertiella). To better understand the
ecology of infections, we used multidimensional scaling analysis to reveal
general patterns of association among parasites, climate, and whole leaf
swallowing-a prevalent self-medicative behaviour at Bulindi linked to control of
nodular worms (Oesophagostomum spp.). Prevalence of parasites varied with climate
in diverse ways. For example, Oesophagostomum sp. was detected in faeces at
higher frequencies with increasing rainfall but was most clearly associated with
periods of low temperature. Certain parasites occurred together within chimpanzee
hosts more or less frequently than expected by chance. For example, the commensal
ciliate Troglodytella abrassarti was negatively associated with Balantidium coli
and Oesophagostomum sp., possibly because the latter taxa make the large
intestine less suitable for T. abrassarti. Whole leaves in faeces showed
independent associations with the prevalence of Oesophagostomum sp.,
Strongyloides sp., and hookworm by microscopic examination, and with egestion of
adult O. stephanostomum by macroscopic inspection. All parasites identified to
species or genus have been reported in wild chimpanzees inhabiting less-disturbed
environments than Bulindi. Nevertheless, several disease-causing taxa infecting
these chimpanzees are potentially transmissible between apes and humans (e.g.
rhabditoid and strongyle nematodes), underscoring the importance of identifying
and reducing risks of pathogen exchange in shared landscapes.
PMID- 28692674
TI - Human brucellosis in Portugal-Retrospective analysis of suspected clinical cases
of infection from 2009 to 2016.
AB - Brucellosis is a zoonosis that is emerging in some regions of the world. Although
brucellosis is a disease of obligatory declaration and is not eradicated in
Portugal, no prevalence data is available in this country. In this study, we
retrospectively analyzed the data available at the Reference Laboratory at the
Portuguese National Institute of Health during the past 7 years (2009-2016) in
order to get insight into the epidemiological scenario of brucellosis in
Portugal. A total of 2313 biological samples from patients with clinical
suspicion of brucellosis were subjected to immunological techniques for
laboratory diagnosis. From 2010 to 2015, a subset of 259 samples was subjected to
molecular methods. According to the available data, 167 out of 2313 (7.2%)
samples had positive serology for Brucella spp. and 43 out of 259 samples (16.6%)
were positive for B. melitensis by real time PCR, being classified as biovar 1
and 3. This study draws attention to the importance of integrating clinical and
laboratory data of human cases in order to increase the efficacy of the response
measures in case of outbreaks.
PMID- 28692675
TI - Cardio-haemodynamic assessment and venous lactate in severe dengue: Relationship
with recurrent shock and respiratory distress.
AB - BACKGROUND: Dengue can cause plasma leakage that may lead to dengue shock
syndrome (DSS). In approximately 30% of DSS cases, recurrent episodes of shock
occur. These patients have a higher risk of fluid overload, respiratory distress
and poor outcomes. We investigated the association of echocardiographically
derived cardiac function and intravascular volume parameters plus lactate levels,
with the outcomes of recurrent shock and respiratory distress in severe dengue.
METHODS/PRINCIPLE FINDINGS: We performed a prospective observational study in
Paediatric and adult ICU, at the Hospital for Tropical Diseases (HTD), Ho Chi
Minh City, Vietnam. Patients with dengue were enrolled within 12 hours of
admission to paediatric or adult ICU. A haemodynamic assessment and portable
echocardiograms were carried out daily for 5 days from enrolment and all
interventions recorded. 102 patients were enrolled; 22 patients did not develop
DSS, 48 had a single episode of shock and 32 had recurrent shock. Patients with
recurrent shock had a higher enrolment pulse than those with 1 episode or no
shock (median: 114 vs. 100 vs. 100 b/min, P = 0.002), significantly lower Stroke
Volume Index (SVI), (median: 21.6 vs. 22.8 vs. 26.8mls/m2, P<0.001) and higher
lactate levels (4.2 vs. 2.9 vs. 2.2 mmol/l, P = 0.001). Higher SVI and worse left
ventricular function (higher Left Myocardial Performance Index) on study days 3-5
was associated with the secondary endpoint of respiratory distress. There was an
association between the total IV fluid administered during the ICU admission and
respiratory distress (OR: 1.03, 95% CI 1.01-1.06, P = 0.001). Admission lactate
levels predicted patients who subsequently developed recurrent shock (P = 0.004),
and correlated positively with the total IV fluid volume received (rho: 0.323, P
= 0.001) and also with admission ALT (rho: 0.764, P<0.001) and AST (rho: 0.773,
P<0.001). CONCLUSIONS/SIGNIFICANCE: Echo-derived intravascular volume assessment
and venous lactate levels can help identify dengue patients at high risk of
recurrent shock and respiratory distress in ICU. These findings may serve to, not
only assist in the management of DSS patients, but also these haemodynamic
endpoints could be used in future dengue fluid intervention trials.
PMID- 28692676
TI - A cross-sectional study of sociodemographic factors and their influence on
quality of life in medical students at Sao Paulo, Brazil.
AB - BACKGROUND: Various sociodemographic factors can affect the quality of life of
medical students and interfere in their ability to study. A deeper understanding
of these factors may facilitate improvements in learning and retention of medical
students. METHODS: We conducted a cross-sectional study of 405 medical students,
representing 65.3% of the total student body (years 1-6), at a private medical
school in Sao Paulo, Brazil. Among the entire study group, 177 students (43.7%)
were male, and 228 (56.3%) were female. The mean age was 23.55 years (SD = 3.98
years, range: 18-40). The World Health Organization Quality of Life-Biomedical
Research and Education Facility (WHOQOL-BREF) scale was used to evaluate the
following sociodemographic factors: age, sex, academic year, daily traveling
time, housing conditions, smoking, weight, height, participant's and his/her
parents' education background, students who had a degree or not and religious
beliefs. The reliability of the WHOQOL-BREF was evaluated using Cronbach's
analysis, and the association of sociodemographic factors with quality of life
was examined using multivariate regression analysis. MAIN RESULTS: Quality of
life was significantly higher in medical students with religious beliefs (beta
0.14 for psychological domain; beta 0.11 for environmental domain) when compared
with that in those with no religious beliefs. BMI was negative associated with
QOL in medical students (beta -0.11 for physical domain; beta -18.9 for the
psychological domain). In both male and female students, longer daily traveling
time was negative related to QOL (beta -0.11 for environmental domain). Having at
least one parent who was a doctor was associated with a better quality of life
(beta 0.17 for environmental domain). Male students presented with significantly
higher mean scores for three of the four domains evaluated (beta 0.20 for
physical domain; beta 0.25 for psychological domain; beta 0.14 for social
domain). CONCLUSION: This study has provided novel insights into the effects of
sociodemographic factors, physical traits, and religious beliefs on the quality
of life of medical students. These findings may facilitate improvements in
physical, psychological, and social support for medical students at a critical
stage in their training, thereby providing tools for student better adjustment to
medical school.
PMID- 28692677
TI - FUX-Sim: Implementation of a fast universal simulation/reconstruction framework
for X-ray systems.
AB - The availability of digital X-ray detectors, together with advances in
reconstruction algorithms, creates an opportunity for bringing 3D capabilities to
conventional radiology systems. The downside is that reconstruction algorithms
for non-standard acquisition protocols are generally based on iterative
approaches that involve a high computational burden. The development of new
flexible X-ray systems could benefit from computer simulations, which may enable
performance to be checked before expensive real systems are implemented. The
development of simulation/reconstruction algorithms in this context poses three
main difficulties. First, the algorithms deal with large data volumes and are
computationally expensive, thus leading to the need for hardware and software
optimizations. Second, these optimizations are limited by the high flexibility
required to explore new scanning geometries, including fully configurable
positioning of source and detector elements. And third, the evolution of the
various hardware setups increases the effort required for maintaining and
adapting the implementations to current and future programming models. Previous
works lack support for completely flexible geometries and/or compatibility with
multiple programming models and platforms. In this paper, we present FUX-Sim, a
novel X-ray simulation/reconstruction framework that was designed to be flexible
and fast. Optimized implementation for different families of GPUs (CUDA and
OpenCL) and multi-core CPUs was achieved thanks to a modularized approach based
on a layered architecture and parallel implementation of the algorithms for both
architectures. A detailed performance evaluation demonstrates that for different
system configurations and hardware platforms, FUX-Sim maximizes performance with
the CUDA programming model (5 times faster than other state-of-the-art
implementations). Furthermore, the CPU and OpenCL programming models allow FUX
Sim to be executed over a wide range of hardware platforms.
PMID- 28692678
TI - Bilateral effects of unilateral cerebellar lesions as detected by voxel based
morphometry and diffusion imaging.
AB - Over the last decades, the importance of cerebellar processing for cortical
functions has been acknowledged and consensus was reached on the strict
functional and structural cortico-cerebellar interrelations. From an anatomical
point of view strictly contralateral interconnections link the cerebellum to the
cerebral cortex mainly through the middle and superior cerebellar peduncle.
Diffusion MRI (dMRI) based tractography has already been applied to address
cortico-cerebellar-cortical loops in healthy subjects and to detect diffusivity
alteration patterns in patients with neurodegenerative pathologies of the
cerebellum. In the present study we used dMRI-based tractography to determine the
degree and pattern of pathological changes of cerebellar white matter
microstructure in patients with focal cerebellar lesions. Diffusion imaging and
high-resolution volumes were obtained in patients with left cerebellar lesions
and in normal controls. Middle cerebellar peduncles and superior cerebellar
peduncles were reconstructed by multi fiber diffusion tractography. From each
tract, measures of microscopic damage were assessed, and despite the presence of
unilateral lesions, bilateral diffusivity differences in white matter tracts were
found comparing patients with normal controls. Consistently, bilateral
alterations were also evidenced in specific brain regions linked to the
cerebellum and involved in higher-level functions. This could be in line with the
evidence that in the presence of unilateral cerebellar lesions, different
cognitive functions can be affected and they are not strictly linked to the side
of the cerebellar lesion.
PMID- 28692679
TI - Early first trimester peripheral blood cell microRNA predicts risk of preterm
delivery in pregnant women: Proof of concept.
AB - OBJECTIVE: We investigated the capacity of first trimester peripheral blood
mononuclear cell (PBMC) microRNA to determine risk of spontaneous preterm birth
among pregnant women. STUDY DESIGN: The study included 39 pregnant women with the
following delivery outcomes: 25 with a full term delivery (38-42 weeks gestation)
14 with spontaneous preterm birth (<38 weeks gestation). Of the 14 women
experiencing spontaneous preterm birth, 7 delivered at 34-<38 weeks gestation
(late preterm) and 7 delivered at <34 weeks gestation (early preterm). Samples
were collected at a mean of 7.9+/-3.0 weeks gestation. Quantitative rtPCR was
performed on 30 selected microRNAs. MicroRNA Risk Scores were calculated and Area
Under the Curve-Receiver-Operational-Characteristic (AUC-ROC) curves derived.
RESULTS: The AUC-ROC for the group delivering preterm (<38 weeks) was 0.95
(p>0.0001). The AUC-ROC for early preterm group (<34 weeks) was 0.98 (p<0.0001)
and the AUC-ROC for the late preterm group (34-<38 weeks) was 0.92 (p<0.0001).
CONCLUSION: Quantification of first trimester peripheral blood PBMC MicroRNA may
provide sensitive and specific prediction of spontaneous preterm birth in
pregnant women. Larger studies are needed for confirmation.
PMID- 28692680
TI - Recurrent myocardial infarction: Mechanisms of free-floating adaptation and
autonomic derangement in networked cardiac neural control.
AB - The cardiac nervous system continuously controls cardiac function whether or not
pathology is present. While myocardial infarction typically has a major and
catastrophic impact, population studies have shown that longer-term risk for
recurrent myocardial infarction and the related potential for sudden cardiac
death depends mainly upon standard atherosclerotic variables and autonomic
nervous system maladaptations. Investigative neurocardiology has demonstrated
that autonomic control of cardiac function includes local circuit neurons for
networked control within the peripheral nervous system. The structural and
adaptive characteristics of such networked interactions define the dynamics and a
new normal for cardiac control that results in the aftermath of recurrent
myocardial infarction and/or unstable angina that may or may not precipitate
autonomic derangement. These features are explored here via a mathematical model
of cardiac regulation. A main observation is that the control environment during
pathology is an extrapolation to a setting outside prior experience. Although
global bounds guarantee stability, the resulting closed-loop dynamics exhibited
while the network adapts during pathology are aptly described as 'free-floating'
in order to emphasize their dependence upon details of the network structure. The
totality of the results provide a mechanistic reasoning that validates the
clinical practice of reducing sympathetic efferent neuronal tone while
aggressively targeting autonomic derangement in the treatment of ischemic heart
disease.
PMID- 28692681
TI - Cervical HPV type-specific pre-vaccination prevalence and age distribution in
Croatia.
AB - The main etiological factor of precancerous lesion and invasive cervical cancer
are oncogenic human papillomaviruses types (HPVs). The objective of this study
was to establish the distribution of the most common HPVs in different cervical
lesions and cancer prior to the implementation of organized population-based
cervical screening and HPV vaccination in Croatia. In this study, 4,432 cervical
specimens, collected through a 16-year period, were tested for the presence of
HPV-DNA by polymerase chain reaction (PCR) with three sets of broad-spectrum
primers and type-specific primers for most common low-risk (LR) types (HPV-6, 11)
and the most common high-risk (HR) types (HPV-16, 18, 31, 33, 45, 52, 58).
Additional 35 archival formalin-fixed, paraffin embedded tissue of cervical
cancer specimens were analyzed using LiPA25 assay. The highest age-specific HPV
prevalence was in the group 18-24 years, which decreased continuously with age
(P<0.0001) regardless of the cytological diagnosis. The prevalence of HR-HPV
types significantly increased (P<0.0001) with the severity of cervical lesions.
HPV-16 was the most common type found with a prevalence (with or without another
HPV-type) of 6.9% in normal cytology, 15.5% in atypical squamous cells of
undetermined significance, 14.4% in low-grade squamous intraepithelial lesions,
33.3% in high-grade squamous intraepithelial lesions, and 60.9% in cervical
cancer specimens (P<0.0001). This study provides comprehensive and extensive data
on the distribution of the most common HPV types among Croatian women, which will
enable to predict and to monitor the impact of HPV-vaccination and to design
effective screening strategies in Croatia.
PMID- 28692682
TI - Low thrombin generation predicts poor prognosis in ischemic stroke patients after
thrombolysis.
AB - Thrombolysis by intravenous recombinant tissue plasminogen activator (rt-PA) is
an effective therapy in acute ischemic stroke (AIS). Thrombin generation test
(TGT) is a global hemostasis test providing information about the speed and
amount of generated thrombin in plasma. Here we aimed to find out whether results
of this test before the initiation of thrombolysis might predict outcomes. Study
population included 120 consecutive AIS patients, all within 4.5 hours of their
symptom onset, who underwent thrombolysis by rt-PA. Blood samples were collected
from all patients upon admission and TGT was performed using platelet poor
plasma. Clinical data of patients including the NIHSS were registered at
admission, day 1 and 7 after therapy. The ASPECT score was assessed using CT
images taken before and 24 hours after thrombolysis. Long-term functional outcome
was defined 3 months after the event by the modified Rankin Scale. Endogenous
Thrombin Potential (ETP) and Peak Thrombin were significantly lower in patients
with cardioembolic IS. Symptomatic intracranial hemorrhage (SICH) was found in 6
patients and was significantly associated with low ETP and Peak Thrombin levels.
A multiple logistic regression model revealed that an ETP result in the lower
quartile is an independent predictor of mortality within the first two weeks (OR:
6.03; 95%CI: 1.2-30.16, p<0.05) and three months after the event (OR: 5.28;
95%CI: 1.27-21.86, p<0.05). Low levels of ETP and Peak Thrombin parameters
increase the risk of therapy associated SICH. A low ETP result is an independent
predictor of short- and long-term mortality following thrombolysis.
PMID- 28692683
TI - Contribution of molecular analysis to the typification of the non-functioning
pituitary adenomas.
AB - AIM: The WHO Classification of Tumours of Endocrine Organs considers the
inmunohistochemical characterization of pituitary adenomas (PA) as mandatory for
patient diagnosis. Recent advances in the knowledge of the molecular patterns of
these tumours could complement this classification with gene expression
profiling. METHODS: Within the context of the Spanish Molecular Registry of
Pituitary Adenomas (REMAH), a multicentre clinical-basic research project, we
analysed the molecular phenotype of 142 PAs with complete IHC and clinical
information. Gene expression levels of all pituitary hormones, type 1
corticotrophin-releasing hormone receptor, dopamine receptors and arginine
vasopressin receptor 1b were measured by quantitative real-time polymerase chain
reaction. In addition, we used three housekeeping genes for normalization and a
pool of nine healthy pituitary glands from autopsies as calibration reference
standard. RESULTS: Based on the clinically functioning PA (FPA: somatotroph,
corticotroph, thyrotroph and lactotroph adenomas), we established the
interquartile range of relative expression for all genes studied in each PA
subtype. That allowed molecularly the different PA subtypes, including the
clinically non-functioning PA (NFPA). Afterwards, we estimated the concordance of
the molecular and immunohistochemical classification with clinical diagnosis in
FPA and between them in NFPA. The kappa values were higher in molecular than in
immunohistochemical classification in FPA and showed a bad concordance in all
NFPA subtypes. CONCLUSIONS: According to these results, the molecular
characterization of the PA complements the IHC analysis, allowing a better
typification of the NFPA.
PMID- 28692684
TI - Comparative cyto-histological study of needle tip aspirates and entry sites after
intravitreal injection using different needle types.
AB - A comparison of the cellular content of needle tip aspirates and entry sites
after transconjunctival intravitreal injection (IVI) using different needle types
was performed. White outbred rats and human cadaver eyes were used for IVI by
hypodermic 27 gauge (G) and 30G needles, and spinal anesthesia Pencan 27G
needles. Aspiration of vitreous for quantitative morphological and cell
cultivation analysis, as well as cyto-histological analysis of aspirates and
entry sites were carried out. The most common cells in the aspirates from all
needle types were conjunctival epithelial-, ciliary body non-pigmented epithelial
and sclerocyte-like cells and granular proteins. Crystallized vitreous specimens
were present in each aspirate. The entry sites of hypodermic needles showed
marked trauma in all wall layers of rat and human eyes accompanied by cellular
destruction and hemorrhages. Pencan 27G needle caused less tissue trauma with
partial reposition of sclerocytes. Transconjunctival IVIs with hypodermic 27G and
30G, and Pencan 27G needles result in trauma of all layers of the eyeball. The
possible consequences of cellular content being cut and injected into the eye, as
well as the entry site wound shape deserve future consideration and improvements.
PMID- 28692685
TI - Intraspecific variability in Phaeocystis antarctica's response to iron and light
stress.
AB - Phaeocystis antarctica is an abundant phytoplankton species in the Southern
Ocean, where growth is frequently limited by iron and light. Being able to grow
under low iron conditions is essential to the species' success, but there have
been hints that this ability differs among clones. Here, we compare the growth,
cell size and chlorophyll a concentrations of four P. antarctica clones cultured
under different iron and light conditions. Iron was provided either as unchelated
iron (Fe') or bound to the bacterial siderophore desferrioxamine B, representing,
respectively, the most and least bioavailable forms of iron which phytoplankton
encounter in the marine environment. The growth rate data demonstrate that the
clones vary in their ability to grow using organically bound iron, and that this
ability is not related to their ability to grow at low inorganic iron
concentrations. These results are consistent at low and high light.
Physiologically, only three of the four clones shrink or decrease the
concentration of chlorophyll a in response to iron limitation, and only one clone
decreases colony formation. Together, our data show that P. antarctica clones 1)
respond to the same degree of iron limitation using different acclimation
strategies, and 2) vary in their ability to grow under the same external iron and
light conditions. This physiological diversity is surprisingly large for isolates
of a single phytoplankton species.
PMID- 28692686
TI - Neuronal correlates of cognitive function in patients with childhood cerebellar
tumor lesions.
AB - While it has been shown that cerebellar tumor lesions have an impact on cognitive
functions, the extent to which they shape distant neuronal pathways is still
largely undescribed. Thus, the present neuroimaging study was designed to
investigate different aspects of cognitive function and their neuronal correlates
in patients after childhood cerebellar tumor surgery. An alertness task, a
working memory task and an incompatibility task were performed by 11 patients
after childhood cerebellar tumor surgery and 17 healthy controls. Neuronal
correlates as reflected by alterations in functional networks during tasks were
assessed using group independent component analysis. We were able to identify
eight networks involved during task performance: default mode network, precuneus,
anterior salience network, executive control network, visual network, auditory
and sensorimotor network and a cerebellar network. For the most 'basic' cognitive
tasks, a weaker task-modulation of default mode network, left executive control
network and the cerebellar network was observed in patients compared to controls.
Results for higher-order tasks are in line with a partial restoration of networks
responsible for higher-order task execution. Our results provide tentative
evidence that the synchronicity of brain activity in patients was at least
partially restored in the course of neuroplastic reorganization, particularly for
networks related to higher-order cognitive processes. The complex activation
patterns underline the importance of testing several cognitive functions to
assess the specificity of cognitive deficits and neuronal reorganization
processes after brain lesions.
PMID- 28692687
TI - Exercise before breakfast increases 24-h fat oxidation in female subjects.
AB - BACKGROUND: Exercise performed in a postprandial state does not increase 24-h fat
oxidation of male and female subjects. Conversely, it has been shown in male
subjects that exercise performed in a postabsorptive state increases 24-h fat
oxidation compared with that in sedentary control and that with exercise trials
performed after breakfast, lunch, or dinner. There is a paucity of study
evaluating the effect of exercise performed in a postabsorptive state in female
subjects. METHOD: Nine young female subjects participated in indirect calorimetry
measurement over 24-h using a room-size metabolic chamber in which subjects
remained sedentary or performed 60 min exercise before breakfast at 50% of
[Formula: see text]. Exercise was accompanied by an increase in energy intake to
ensure that subjects were in a similar state of energy balance over 24 h for the
two trials. FINDINGS: Compared with the sedentary condition, exercise performed
before breakfast increased 24-h fat oxidation (519 +/- 37 vs. 400 +/- 41
kcal/day). Time courses of relative energy balance differed between trials with
transient negative energy balance observed before breakfast. The lowest values of
relative energy balance observed during the 24-h calorimetry, i.e., transient
energy deficit, were greater in exercise trials than in sedentary trials. The
transient deficit in carbohydrate balance was also observed before breakfast, and
magnitude of the deficit was greater in exercise trial compared to that of
sedentary trial. INTERPRETATION: Under energy-balanced conditions, exercise
performed in a post-absorptive state increases 24-h fat oxidation in female
subjects. The effect of exercise performed before breakfast can be attributed to
nutritional state: a transient deficit in energy and carbohydrate at the end of
exercise.
PMID- 28692688
TI - Addressing uncertainty in modelling cumulative impacts within maritime spatial
planning in the Adriatic and Ionian region.
AB - Maritime spatial planning (MSP) is envisaged as a tool to apply an ecosystem
based approach to the marine and coastal realms, aiming at ensuring that the
collective pressure of human activities is kept within acceptable limits.
Cumulative impacts (CI) assessment can support science-based MSP, in order to
understand the existing and potential impacts of human uses on the marine
environment. A CI assessment includes several sources of uncertainty that can
hinder the correct interpretation of its results if not explicitly incorporated
in the decision-making process. This study proposes a three-level methodology to
perform a general uncertainty analysis integrated with the CI assessment for MSP,
applied to the Adriatic and Ionian Region (AIR). We describe the nature and level
of uncertainty with the help of expert judgement and elicitation to include all
of the possible sources of uncertainty related to the CI model with assumptions
and gaps related to the case-based MSP process in the AIR. Next, we use the
results to tailor the global uncertainty analysis to spatially describe the
uncertainty distribution and variations of the CI scores dependent on the CI
model factors. The results show the variability of the uncertainty in the AIR,
with only limited portions robustly identified as the most or the least impacted
areas under multiple model factors hypothesis. The results are discussed for the
level and type of reliable information and insights they provide to decision
making. The most significant uncertainty factors are identified to facilitate the
adaptive MSP process and to establish research priorities to fill knowledge gaps
for subsequent planning cycles. The method aims to depict the potential CI
effects, as well as the extent and spatial variation of the data and scientific
uncertainty; therefore, this method constitutes a suitable tool to inform the
potential establishment of the precautionary principle in MSP.
PMID- 28692689
TI - Factors influencing maternal nutrition practices in a large scale maternal,
newborn and child health program in Bangladesh.
AB - Improving maternal nutrition practices during pregnancy is essential to save
lives and improve health outcomes for both mothers and babies. This paper
examines the maternal, household, and health service factors influencing maternal
nutrition practices in the context of a large scale maternal, newborn, and child
health (MNCH) program in Bangladesh. Data were from a household survey of
pregnant (n = 600) and recently delivered women (n = 2,000). Multivariate linear
and logistic regression analyses were used to examine the determinants of three
outcomes: consumption of iron and folic acid (IFA) tablets, calcium tablets, and
diverse diets. Women consumed 94 +/- 68 IFA and 82 +/- 66 calcium tablets (out of
180 as recommended) during pregnancy, and only half of them consumed an
adequately diverse diet. Good nutrition knowledge was the key maternal factor
associated with higher consumption of IFA (beta = 32.5, 95% CI: 19.5, 45.6) and
calcium tablets (beta ~31.9, 95% CI: 20.9, 43.0) and diverse diet (OR = 1.8, 95%
CI: 1.0-3.1), compared to poor knowledge. Women's self-efficacy in achieving the
recommended practices and perception of enabling social norms were significantly
associated with dietary diversity. At the household level, women who reported a
high level of husband's support were more likely to consume IFA (beta = 25.0, 95%
CI: 18.0, 32.1) and calcium (beta = 26.6, 95% CI: 19.4, 33.7) tablets and diverse
diet (OR = 1.9, 95% CI: 1.2, 3.3), compared to those who received low support.
Health service factors associated with higher intakes of IFA and calcium tablets
were early and more prenatal care visits and receipt of free supplements.
Combined exposure to several of these factors was attributed to the consumption
of an additional 46 IFA and 53 calcium tablets and 17% higher proportions of
women consuming diverse diets. Our study shows that improving knowledge, self
efficacy and perceptions of social norms among pregnant women, and increasing
husbands' support, early registration in prenatal care, and provision of free
supplements will largely improve maternal nutrition practices.
PMID- 28692690
TI - Risk of surgical site infection, acute kidney injury, and Clostridium difficile
infection following antibiotic prophylaxis with vancomycin plus a beta-lactam
versus either drug alone: A national propensity-score-adjusted retrospective
cohort study.
AB - BACKGROUND: The optimal regimen for perioperative antimicrobial prophylaxis is
controversial. Use of combination prophylaxis with a beta-lactam plus vancomycin
is increasing; however, the relative risks and benefits associated with this
strategy are unknown. Thus, we sought to compare postoperative outcomes following
administration of 2 antimicrobials versus a single agent for the prevention of
surgical site infections (SSIs). Potential harms associated with combination
regimens, including acute kidney injury (AKI) and Clostridium difficile infection
(CDI), were also considered. METHODS AND FINDINGS: Using a multicenter, national
Veterans Affairs (VA) cohort, all patients who underwent cardiac, orthopedic
joint replacement, vascular, colorectal, and hysterectomy procedures during the
period from 1 October 2008 to 30 September 2013 and who received planned manual
review of perioperative antimicrobial prophylaxis regimen and manual review for
the 30-day incidence of SSI were included. Using a propensity-adjusted log
binomial regression model stratified by type of surgical procedure, the
association between receipt of 2 antimicrobials (vancomycin plus a beta-lactam)
versus either single agent alone (vancomycin or a beta-lactam) and SSI was
evaluated. Measures of association were adjusted for age, diabetes, smoking,
American Society of Anesthesiologists score, preoperative methicillin-resistant
Staphylococcus aureus (MRSA) status, and receipt of mupirocin. The 7-day
incidence of postoperative AKI and 90-day incidence of CDI were also measured. In
all, 70,101 procedures (52,504 beta-lactam only, 5,089 vancomycin only, and
12,508 combination) with 2,466 (3.5%) SSIs from 109 medical centers were
included. Among cardiac surgery patients, combination prophylaxis was associated
with a lower incidence of SSI (66/6,953, 0.95%) than single-agent prophylaxis
(190/12,834, 1.48%; crude risk ratio [RR] 0.64, 95% CI 0.49, 0.85; adjusted RR
0.61, 95% CI 0.46, 0.83). After adjusting for SSI risk, no association between
receipt of combination prophylaxis and SSI was found for the other types of
surgeries evaluated, including orthopedic joint replacement procedures. In MRSA
colonized patients undergoing cardiac surgery, SSI occurred in 8/346 (2.3%)
patients who received combination prophylaxis versus 4/100 (4.0%) patients who
received vancomycin alone (crude RR 0.58, 95% CI 0.18, 1.88). Among MRSA-negative
and -unknown cardiac surgery patients, SSIs occurred in 58/6,607 (0.9%) patients
receiving combination prophylaxis versus 146/10,215 (1.4%) patients who received
a beta-lactam alone (crude RR 0.61, 95% CI 0.45, 0.83). Based on these
associations, the number needed to treat to prevent 1 SSI in MRSA-colonized
patients is estimated to be 53, compared to 176 in non-MRSA patients. CDI
incidence was similar in both exposure groups. Across all types of surgical
procedures, risk of AKI was increased in the combination antimicrobial
prophylaxis group (2,971/12,508 [23.8%] receiving combination versus 1,058/5,089
[20.8%] receiving vancomycin alone versus 7,314/52,504 [13.9%] receiving beta
lactam alone). We found a significant association between absolute risk of AKI
and receipt of combination regimens across all types of procedures. If the
observed association is causal, the number needed to harm for severe AKI
following cardiac surgery would be 167. The major limitation of our investigation
is that it is an observational study in a predominantly male population, which
may limit generalizability and lead to unmeasured confounding. CONCLUSIONS: There
are benefits but also unintended consequences of antimicrobial and infection
prevention strategies aimed at "getting to zero" healthcare-associated
infections. In our study, combination prophylaxis was associated with both
benefits (reduction in SSIs following cardiac surgical procedures) and harms
(increase in postoperative AKI). In cardiac surgery patients, the difference in
risk-benefit profile by MRSA status suggests that MRSA-screening-directed
prophylaxis may optimize benefits while minimizing harms in this selected
population. More information about long-term outcomes and patient and societal
preferences regarding risk of SSI versus risk of AKI is needed to improve
clinical decision-making.
PMID- 28692691
TI - Extracting time-frequency feature of single-channel vastus medialis EMG signals
for knee exercise pattern recognition.
AB - The EMG signal indicates the electrophysiological response to daily living of
activities, particularly to lower-limb knee exercises. Literature reports have
shown numerous benefits of the Wavelet analysis in EMG feature extraction for
pattern recognition. However, its application to typical knee exercises when
using only a single EMG channel is limited. In this study, three types of knee
exercises, i.e., flexion of the leg up (standing), hip extension from a sitting
position (sitting) and gait (walking) are investigated from 14 healthy untrained
subjects, while EMG signals from the muscle group of vastus medialis and the
goniometer on the knee joint of the detected leg are synchronously monitored and
recorded. Four types of lower-limb motions including standing, sitting, stance
phase of walking, and swing phase of walking, are segmented. The Wavelet
Transform (WT) based Singular Value Decomposition (SVD) approach is proposed for
the classification of four lower-limb motions using a single-channel EMG signal
from the muscle group of vastus medialis. Based on lower-limb motions from all
subjects, the combination of five-level wavelet decomposition and SVD is used to
comprise the feature vector. The Support Vector Machine (SVM) is then configured
to build a multiple-subject classifier for which the subject independent accuracy
will be given across all subjects for the classification of four types of lower
limb motions. In order to effectively indicate the classification performance,
EMG features from time-domain (e.g., Mean Absolute Value (MAV), Root-Mean-Square
(RMS), integrated EMG (iEMG), Zero Crossing (ZC)) and frequency-domain (e.g.,
Mean Frequency (MNF) and Median Frequency (MDF)) are also used to classify lower
limb motions. The five-fold cross validation is performed and it repeats fifty
times in order to acquire the robust subject independent accuracy. Results show
that the proposed WT-based SVD approach has the classification accuracy of
91.85%+/-0.88% which outperforms other feature models.
PMID- 28692692
TI - Geographic strain differentiation of Schistosoma japonicum in the Philippines
using microsatellite markers.
AB - BACKGROUND: Microsatellites have been found to be useful in determining genetic
diversities of various medically-important parasites which can be used as basis
for an effective disease management and control program. In Asia and Africa, the
identification of different geographical strains of Schistosoma japonicum, S.
haematobium and S. mansoni as determined through microsatellites could pave the
way for a better understanding of the transmission epidemiology of the parasite.
Thus, the present study aims to apply microsatellite markers in analyzing the
populations of S. japonicum from different endemic areas in the Philippines for
possible strain differentiation. METHODOLOGY/ PRINCIPAL FINDINGS: Experimental
mice were infected using the cercariae of S. japonicum collected from infected
Oncomelania hupensis quadrasi snails in seven endemic municipalities. Adult worms
were harvested from infected mice after 45 days of infection and their DNA
analyzed against ten previously characterized microsatellite loci. High genetic
diversity was observed in areas with high endemicity. The degree of genetic
differentiation of the parasite population between endemic areas varies.
Geographical separation was considered as one of the factors accounting for the
observed difference between populations. Two subgroups have been observed in one
of the study sites, suggesting that co-infection with several genotypes of the
parasite might be present in the population. Clustering analysis showed no
particular spatial structuring between parasite populations from different
endemic areas. This result could possibly suggest varying degrees of effects of
the ongoing control programs and the existing gene flow in the populations, which
might be attributed to migration and active movement of infected hosts from one
endemic area to another. CONCLUSIONS/ SIGNIFICANCE: Based on the results of the
study, it is reasonable to conclude that genetic diversity could be one possible
criterion to assess the infection status in highly endemic areas. Genetic
surveillance using microsatellites is therefore important to predict the ongoing
gene flow and degree of genetic diversity, which indirectly reflects the success
of the control program in schistosomiasis-endemic areas.
PMID- 28692693
TI - Landscape context and the biophysical response of rivers to dam removal in the
United States.
AB - Dams have been a fundamental part of the U.S. national agenda over the past two
hundred years. Recently, however, dam removal has emerged as a strategy for
addressing aging, obsolete infrastructure and more than 1,100 dams have been
removed since the 1970s. However, only 130 of these removals had any ecological
or geomorphic assessments, and fewer than half of those included before- and
after-removal (BAR) studies. In addition, this growing, but limited collection of
dam-removal studies is limited to distinct landscape settings. We conducted a
meta-analysis to compare the landscape context of existing and removed dams and
assessed the biophysical responses to dam removal for 63 BAR studies. The highest
concentration of removed dams was in the Northeast and Upper Midwest, and most
have been removed from 3rd and 4th order streams, in low-elevation (< 500 m) and
low-slope (< 5%) watersheds that have small to moderate upstream watershed areas
(10-1000 km2) with a low risk of habitat degradation. Many of the BAR-studied
removals also have these characteristics, suggesting that our understanding of
responses to dam removals is based on a limited range of landscape settings,
which limits predictive capacity in other environmental settings. Biophysical
responses to dam removal varied by landscape cluster, indicating that landscape
features are likely to affect biophysical responses to dam removal. However,
biophysical data were not equally distributed across variables or clusters,
making it difficult to determine which landscape features have the strongest
effect on dam-removal response. To address the inconsistencies across dam-removal
studies, we provide suggestions for prioritizing and standardizing data
collection associated with dam removal activities.
PMID- 28692694
TI - Renal replacement therapy practices for patients with acute kidney injury in
China.
AB - Recent data indicate AKI is very common among hospitalized Chinese patients and
continuous renal replacement therapy (CRRT) is increasingly offered for
treatment. However, only anecdotal information regarding CRRT's use in relation
to other modalities and the specific manner in which it is prescribed exists
currently. This report summarizes the results of a comprehensive physician survey
designed to characterize contemporary dialytic management of AKI patients in
China, especially with respect to the utilization of CRRT. The survey queried
both nephrologists and critical care physicians across a wide spectrum of
hospitals about factors influencing initial RRT modality selection, especially
patient clinical characteristics and willingness to receive RRT, treatment
location, and institutional capabilities. For patients initially treated with
CRRT, data related to indication, timing of treatment initiation, dose,
anticoagulation technique, and duration of therapy were also collected. Among AKI
patients considered RRT candidates, the survey indicated 15.1% (95% CI, 12.3%
17.9%) did not actually receive dialysis at Chinese hospitals. The finding was
largely attributed to prohibitively high therapy costs in the view of patients or
their families. The survey confirmed the dichotomy in RRT delivery in China,
occurring both in the nephrology department (with nephrologists responsible) and
the intensive care unit (with critical care physicians responsible). For all
patients who were offered and received RRT, the survey participants reported
63.9% (56.4%-71.3%) were treated initially with CRRT and 24.8% (19.2%-30.3%) with
intermittent hemodialysis (HD) (P<0.001). The mean percentage of patients
considered hemodynamically unstable at RRT initiation was 36.2% (31.3%-41.1%),
although this figure was two-fold higher in patients treated initially with CRRT
(43.1%; 35.8%-50.4%) in comparison to those initially treated with HD (22.4%;
16.4%-28.4%)(P<0.001). An overwhelming majority of intensive care patients were
treated initially with CRRT (86.6%; 79.8-93.4%) while it was the initial modality
in only 44.6% (33.5-55.7%) of patients treated in a nephrology department
(P<0.001). Approximately 70% of respondents overall reported prescribing a CRRT
dose in the range of 20-30 mL/kg/hr while approximately 20% of prescriptions fell
above this range. Daily prescribed therapy duration demonstrated a marked
divergence from values reported in the literature and standard clinical practice.
Overall, the most common average prescribed value (50% of respondents) fell in
the 10-20 hr range, with only 18% in the 20-24 hr range. Moreover, 32% of
respondents reported an average prescribed value of less than 10 hrs per day.
While the percentages for the 10-20 hrs range were essentially the same for
nephrology and ICU programs, a daily duration of less than 10 hrs was much more
common in nephrology programs (48.0%; 38.3%-57.9%) versus ICU programs (16%;
10.0%-24.6%)(P<0.001). Our analysis demonstrates both similarities and
differences between RRT practices for AKI in China and those in the developed
world. While some differences are driven by non-medical factors, future studies
should explore these issues further as Chinese RRT practices are harmonized with
those in the rest of the world.
PMID- 28692695
TI - Cancer in Korean patients with end-stage renal disease: A 7-year follow-up.
AB - BACKGROUND: The effectiveness of dialysis on the incidence of cancer in patients
with end-stage renal disease (ESRD) remains to be clarified. In this study, we
evaluated the incidence rate and type of cancer among patients with ESRD,
compared to the general population, through a prospective 7-year follow-up. We
also calculated the cumulative incidence rate of cancer associated with ESRD,
with stratification to control for the competing risk of death. METHODS: This
prospective observational cohort study was conducted using data from a nationwide
study on patients with ESRD in Korea. A total of 5,235 patients, >=18 years old,
with ESRD were identified from the national registry as being treated by dialysis
between August 2008 and December 2014. The standardized incidence ratio (SIR) and
cumulative incidence rate of specific cancers were evaluated and compared to the
general population. RESULTS: A total of 5,235 participants were included. During
the 7 year observation period, 116 (2.2%) participants had been diagnosed as
cancer. The SIR of overall cancer was 0.94 [95% confidence interval (CI), 0.72
1.19] and was comparable to the rate for the general population. Although the
digestive organs were the most frequent site of a primary site cancer (N = 39,
33.6%), the SIR was highest for urinary tract cancer [4.7, 95% CI, 2.42-8.19].
The five year standardized cumulative incidence of cancer was higher for females
than for males, and for non-diabetic compared to diabetic causes of ESRD. We
estimated that the five year standardized cumulative incidence was highest [8.4,
95% CI, 5.07-13.75] in patients with ESRD, caused by glomerulonephritis.
CONCLUSION: A screening program should be necessary for urinary tract cancer in
Korean patients with ESRD. Cancer screening programs for patients with ESRD in
Korea should be emphasized on female patients and patients with non-diabetic
ESRD.
PMID- 28692696
TI - Corticosterone response to gestational stress and postpartum memory function in
mice.
AB - Maternal stress is a common adversity during pregnancy. Gestational
corticosterone alternations are thought to contribute to the etiology of
postpartum behavioral disturbances. However, the impact of stress during
pregnancy, in particular noise exposure, on gestational corticosterone
fluctuations and spatial cognition in postpartum mice has not been fully
understood yet. We hypothesized that noise exposure during pregnancy negatively
affects gestational corticosterone levels and postpartum memory function in the
dams similar to the physical stressors. Pregnant C57BL/6 mice were randomly
assigned to either one of two stress conditions or a control condition. The noise
stress (NS) was induced by presenting a loud intermittent 3000 Hz frequency on
gestational days (GDs) 12, 14, and 16 for 24 hours, whereas the physical stress
(PS) consisted of restraint and exposure to an elevated platform on GDs 12-16.
Plasma corticosterone level was collected on GDs 11 and 17, and Morris water task
(MWT) was carried out 30 days after parturition. Compared to the control group,
the level of corticosterone in the stressed groups was significantly increased on
GD17 relative to GD11. Significantly longer swim time and lower swim speed were
observed in both stressed groups relative to the control group. Probe time was
significantly shorter in the NS group than the other groups. The delta
corticosterone level was significantly correlated with the swim time as well as
the probe time in the three groups. Given the results, the adverse effects of
gestational noise exposure on the hypothalamic pituitary-adrenal (HPA) axis
activation and postpartum spatial learning and memory function were as large as/
or a bit stronger than the physical stresses. The findings suggest the
significance of conservation against loud noise exposure in daily living, as well
as need to further notice to the different aspects of gestational stress in
mothers' behavior like offspring.
PMID- 28692697
TI - [Formula: see text]: Oblivious similarity based searching for encrypted data
outsourced to an untrusted domain.
AB - Public cloud storage services are becoming prevalent and myriad data sharing,
archiving and collaborative services have emerged which harness the pay-as-you-go
business model of public cloud. To ensure privacy and confidentiality often
encrypted data is outsourced to such services, which further complicates the
process of accessing relevant data by using search queries. Search over encrypted
data schemes solve this problem by exploiting cryptographic primitives and secure
indexing to identify outsourced data that satisfy the search criteria. Almost all
of these schemes rely on exact matching between the encrypted data and search
criteria. A few schemes which extend the notion of exact matching to similarity
based search, lack realism as those schemes rely on trusted third parties or due
to increase storage and computational complexity. In this paper we propose
Oblivious Similarity based Search ([Formula: see text]) for encrypted data. It
enables authorized users to model their own encrypted search queries which are
resilient to typographical errors. Unlike conventional methodologies, [Formula:
see text] ranks the search results by using similarity measure offering a better
search experience than exact matching. It utilizes encrypted bloom filter and
probabilistic homomorphic encryption to enable authorized users to access
relevant data without revealing results of search query evaluation process to the
untrusted cloud service provider. Encrypted bloom filter based search enables
[Formula: see text] to reduce search space to potentially relevant encrypted data
avoiding unnecessary computation on public cloud. The efficacy of [Formula: see
text] is evaluated on Google App Engine for various bloom filter lengths on
different cloud configurations.
PMID- 28692699
TI - Multiple quay cranes scheduling for double cycling in container terminals.
AB - Double cycling is an efficient tool to increase the efficiency of quay crane (QC)
in container terminals. In this paper, an optimization model for double cycling
is developed to optimize the operation sequence of multiple QCs. The objective is
to minimize the makespan of the ship handling operation considering the ship
balance constraint. To solve the model, an algorithm based on Lagrangian
relaxation is designed. Finally, we compare the efficiency of the Lagrangian
relaxation based heuristic with the branch-and-bound method and a genetic
algorithm using instances of different sizes. The results of numerical
experiments indicate that the proposed model can effectively reduce the unloading
and loading times of QCs. The effects of the ship balance constraint are more
notable when the number of QCs is high.
PMID- 28692698
TI - Nitric oxide attenuates overexpression of Gialpha proteins in vascular smooth
muscle cells from SHR: Role of ROS and ROS-mediated signaling.
AB - Vascular smooth muscle cells (VSMC) from spontaneously hypertensive rats (SHR)
exhibit decreased levels of nitric oxide (NO) that may be responsible for the
overexpression of Gialpha proteins that has been shown as a contributing factor
for the pathogenesis of hypertension in SHR. The present study was undertaken to
investigate if increasing the intracellular levels of NO by NO donor S-Nitroso-N
acetyl-DL-penicillamine (SNAP) could attenuate the enhanced expression of Gialpha
proteins in VSMC from SHR and explore the underlying mechanisms responsible for
this response. The expression of Gialpha proteins and phosphorylation of ERK1/2,
growth factor receptors and c-Src was determined by Western blotting using
specific antibodies. Treatment of VSMC from SHR with SNAP for 24 hrs decreased
the enhanced expression of Gialpha-2 and Gialpha-3 proteins and
hyperproliferation that was not reversed by 1H (1, 2, 4) oxadiazole (4, 3-a)
quinoxalin-1-one (ODQ), an inhibitor of soluble guanylyl cyclase, however,
PD98059, a MEK inhibitor restored the SNAP-induced decreased expression of
Gialpha proteins towards control levels. In addition, the increased production of
superoxide anion, NAD(P)H oxidase activity, overexpression of AT1 receptor, Nox4,
p22phox and p47phox proteins, enhanced levels of TBARS and protein carbonyl,
increased phosphorylation of PDGF-R, EGF-R, c-Src and ERK1/2 in VSMC from SHR
were all decreased to control levels by SNAP treatment. These results suggest
that NO decreased the enhanced expression of Gialpha-2/3 proteins and
hyperproliferation of VSMC from SHR by cGMP-independent mechanism and involves
ROS and ROS-mediated transactivation of EGF-R/PDGF-R and MAP kinase signaling
pathways.
PMID- 28692700
TI - Noise, multisensory integration, and previous response in perceptual
disambiguation.
AB - Sensory information about the state of the world is generally ambiguous.
Understanding how the nervous system resolves such ambiguities to infer the
actual state of the world is a central quest for sensory neuroscience. However,
the computational principles of perceptual disambiguation are still poorly
understood: What drives perceptual decision-making between multiple equally valid
solutions? Here we investigate how humans gather and combine sensory information
within and across modalities-to disambiguate motion perception in an ambiguous
audiovisual display, where two moving stimuli could appear as either streaming
through, or bouncing off each other. By combining psychophysical classification
tasks with reverse correlation analyses, we identified the particular
spatiotemporal stimulus patterns that elicit a stream or a bounce percept,
respectively. From that, we developed and tested a computational model for uni-
and multi-sensory perceptual disambiguation that tightly replicates human
performance. Specifically, disambiguation relies on knowledge of prototypical
bouncing events that contain characteristic patterns of motion energy in the
dynamic visual display. Next, the visual information is linearly integrated with
auditory cues and prior knowledge about the history of recent perceptual
interpretations. What is more, we demonstrate that perceptual decision-making
with ambiguous displays is systematically driven by noise, whose random patterns
not only promote alternation, but also provide signal-like information that
biases perception in highly predictable fashion.
PMID- 28692701
TI - Molecular features of influenza A (H1N1)pdm09 prevalent in Mexico during winter
seasons 2012-2014.
AB - Since the emergence of the pandemic H1N1pdm09 virus in Mexico and California,
biannual increases in the number of cases have been detected in Mexico. As
observed in previous seasons, pandemic A/H1N1 09 virus was detected in severe
cases during the 2011-2012 winter season and finally, during the 2013-2014 winter
season it became the most prevalent influenza virus. Molecular and phylogenetic
analyses of the whole viral genome are necessary to determine the antigenic and
pathogenic characteristics of influenza viruses that cause severe outcomes of the
disease. In this paper, we analyzed the evolution, antigenic and genetic drift of
Mexican isolates from 2009, at the beginning of the pandemic, to 2014. We found a
clear variation of the virus in Mexico from the 2011-2014 season due to different
markers and in accordance with previous reports. In this study, we identified 13
novel substitutions with important biological effects, including virulence, T
cell epitope presented by MHC and host specificity shift and some others
substitutions might have more than one biological function. The systematic
monitoring of mutations on whole genome of influenza A pH1N1 (2009) virus
circulating at INER in Mexico City might provide valuable information to predict
the emergence of new pathogenic influenza virus.
PMID- 28692702
TI - Impaired insula functional connectivity associated with persistent pain
perception in patients with complex regional pain syndrome.
AB - Given that the insula plays a contributory role in the perception of chronic
pain, we examined the resting-state functional connectivity between the insular
cortex and other brain regions to investigate neural underpinnings of persisting
perception of background pain in patients with complex regional pain syndrome
(CRPS). A total of 25 patients with CRPS and 25 matched healthy controls
underwent functional magnetic resonance imaging at rest. With the anterior and
posterior insular cortices as seed regions, we compared the strength of the
resting-state functional connectivity between the two groups. Functional
connectivity between the anterior and posterior insular cortices and the
postcentral and inferior frontal gyri, cingulate cortices was reduced in patients
with CRPS compared with controls. Additionally, greater reductions in functional
connectivity between the anterior insula and right postcentral gyrus were
associated with more severe sensory pain in patients with CRPS (short-form McGill
Pain Questionnaire sensory subscores, r = -.517, P = .023). The present results
imply a possible role of the insula in aberrant processing of pain information in
patients with CRPS. The findings suggest that a functional derangement of the
connection between one of the somatosensory cortical functions of perception and
one of the insular functions of awareness can play a significant role in the
persistent experience of regional pain that is not confined to a specific nerve
territory.
PMID- 28692703
TI - Physical examination skills training: Faculty staff vs. patient instructor
feedback-A controlled trial.
AB - BACKGROUND: Standardized patients are widely used in training of medical
students, both in teaching and assessment. They also frequently lead complete
training sessions delivering physical examination skills without the aid of
faculty teaching staff-acting as "patient instructors" (PIs). An important part
of this training is their ability to provide detailed structured feedback to
students which has a strong impact on their learning success. Yet, to date no
study has assessed the quality of physical examination related feedback by PIs.
Therefore, we conducted a randomized controlled study comparing feedback of PIs
and faculty staff following a physical examination assessed by students and video
assessors. METHODS: 14 PIs and 14 different faculty staff physicians both
delivered feedback to 40 medical students that had performed a physical
examination on the respective PI while the physicians observed the performance.
The physical examination was rated by two independent video assessors to provide
an objective performance standard (gold standard). Feedback of PI and physicians
was content analyzed by two different independent video assessors based on a
provided checklist and compared to the performance standard. Feedback of PIs and
physicians was also rated by medical students and video assessors using a
questionnaire consisting of 12 items. RESULTS: There was no statistical
significant difference concerning overall matching of physician or PI feedback
with gold standard ratings by video assessment (p = .219). There was also no
statistical difference when focusing only on items that were classified as major
key steps (p = .802), mistakes or parts that were left out during physical
examination (p = .219) or mistakes in communication items (p = .517). The
feedback of physicians was significantly better rated than PI feedback both by
students (p = .043) as well as by video assessors (p = .034). CONCLUSIONS: In
summary, our study demonstrates that trained PIs are able to provide feedback of
equal quantitative value to that of faculty staff physicians with regard to a
physical examination performed on them. However, both the students and the video
raters judged the quality of the feedback given by the physicians to be
significantly better than that of the PIs.
PMID- 28692704
TI - Oral cancer via the bargain bin: The risk of oral cancer associated with a
smokeless tobacco product (Naswar).
AB - In the wake of smokeless tobacco (SLT) being advocated as a mean of tobacco harm
reduction, it is pertinent to establish individual health risks associated with
each SLT product. This case-control study was aimed at assessing the risk of oral
cancer associated with a smokeless tobacco product (Naswar). The study was
conducted from September 2014 till May 2015 in Khyber Pakhtunkhwa, Pakistan.
Exposure and covariate information was collected through a structured
questionnaire. Conditional logistic regression was used to calculate odds ratios
(OR) along with their 95% confidence intervals (CI). 84 oral cancer cases (62%
males) and 174 age- and sex-matched controls were recruited. Ever users of Naswar
had more than a 20-fold higher risk of oral cancer compared to never-users (OR
21.2, 95% CI 8.4-53.8). Females had a higher risk of oral cancer with the use of
Naswar (OR 29.0, 95% CI 5.4-153.9) as compared to males (OR 21.0, 95% CI 6.1
72.1). Based on this result, 68% (men) and 38% (women) of the oral cancer burden
in Pakistan is attributable to Naswar. The risk estimates observed in this study
are comparable to risk estimates reported by previous studies on other forms of
SLT use and the risk of oral cancer in Pakistan. The exposure-response
relationship also supports a strong role of Naswar in the etiology of oral cancer
in Pakistan. Although still requiring further validation through independent
studies, these findings may be used for smokeless tobacco control in countries
where Naswar use is common.
PMID- 28692705
TI - Right wing authoritarianism is associated with race bias in face detection.
AB - Racial discrimination can be observed in a wide range of psychological processes,
including even the earliest phases of face detection. It remains unclear,
however, whether racially-biased low-level face processing is influenced by
ideologies, such as right wing authoritarianism or social dominance orientation.
In the current study, we hypothesized that socio-political ideologies such as
these can substantially predict perceptive racial bias during early perception.
To test this hypothesis, 67 participants detected faces within arrays of neutral
objects. The faces were either Caucasian (in-group) or North African (out-group)
and either had a neutral or angry expression. Results showed that participants
with higher self-reported right-wing authoritarianism were more likely to show
slower response times for detecting out- vs. in-groups faces. We interpreted our
results according to the Dual Process Motivational Model and suggest that socio
political ideologies may foster early racial bias via attentional disengagement.
PMID- 28692707
TI - Can Patients Make Recordings of Medical Encounters?: What Does the Law Say?
PMID- 28692706
TI - Predictors for bile duct stone recurrence after endoscopic extraction for naive
major duodenal papilla: A cohort study.
AB - BACKGROUND: Predictors for bile duct stone recurrence after endoscopic stone
extraction have not yet been clearly defined and a study investigating naive
major duodenal papilla is warranted because studies focusing only on naive major
duodenal papilla are rare. The aim of this study was to observe the long-term
outcomes of endoscopic bile duct stone extraction for naive major duodenal
papilla and to assess the predictors for recurrence. METHODS: This was a
retrospective cohort study that consisted of 384 patients with naive papilla who
underwent initial endoscopic bile duct stone extraction. Patients were followed
up in outpatient department subsequent to complete stone clearance. Recurrence
was defined as symptomatic repeated stone formation observed at least three
months after the procedure. Stone recurrence, predictors of recurrence, and the
recurrence rate, depending on each endoscopic treatment for major duodenal
papilla, were examined. RESULTS: In this study, 34 patients (8.9%) developed
stone recurrence. The median time to recurrence was 439 days. Periampullary
diverticulum and multiple stones were strong predictors of bile duct stone
recurrence (RR, 5.065; 95% CI, 2.435-10.539 and RR: 2.4401; 95% CI: 1.0946
5.4396, respectively). The above two factors were independent predictors of stone
recurrence as per logistic regression analysis adjusted for confounders
(Periampullary diverticulum: OR, 7.768; 95% CI, 3.27-18.471; multiple stones: OR,
4.144; 95% CI, 1.33-12.915). No recurrence was observed after endoscopic
papillary large balloon dilatation (0/20), whereas recurrence was observed in 7
patients after endoscopic papillary balloon dilatation (7/45) and in 27 patients
after endoscopic sphincterotomy (27/319). However, these differences were not
statistically significant (p = 0.105). CONCLUSIONS: We determined that the
presence of periampullary diverticulum and multiple stones are strong predictors
for recurrence after endoscopic stone extraction. Moreover, endoscopic papillary
large balloon dilatation tended to be correlated with non-recurrence of bile duct
stone.
PMID- 28692708
TI - Safety and Efficacy of Bortezomib in Patients With Highly Relapsing Neuromyelitis
Optica Spectrum Disorder.
PMID- 28692709
TI - Baby-Led Weaning-Safe and Effective but Not Preventive of Obesity.
PMID- 28692710
TI - Association of Plasma Total Tau Level With Cognitive Decline and Risk of Mild
Cognitive Impairment or Dementia in the Mayo Clinic Study on Aging.
AB - Importance: The utility of plasma total tau level as a prognostic marker for
cognitive decline and dementia is not well understood. Objectives: To determine
(1) the association between plasma total tau level, cognitive decline, and risk
of mild cognitive impairment (MCI) and dementia; (2) whether this association
differs by the presence of elevated brain amyloid beta (Abeta); and (3) whether
plasma total tau level is associated with cognitive decline over a short interval
of 15 months. Design, Setting, and Participants: The present analyses included
458 participants who were enrolled in a population-based cohort study between
October 2008 and June 2013. All included participants had available plasma total
tau levels, Abeta positron emission tomography imaging, and a complete
neuropsychological examine at the same visit, as well as at least 1 follow-up
visit. Exposures: Concentration of plasma total tau. Main Outcomes and Measures:
Risk of MCI and dementia; global and domain-specific cognitive decline. Results:
Of the 458 participants, 287 (62.7%) were men; mean (SD) age was 80.6 (5.6)
years. Among cognitively normal (CN) participants oversampled for elevated brain
Abeta, both the middle (hazard ratio [HR], 2.43; 95% CI, 1.25-4.72) and highest
(HR, 2.02; 95% CI, 1.01-4.06) tertiles of plasma total tau level, compared with
the lowest, were associated with an increased risk of MCI. Among participants
with MCI, higher plasma total tau levels were not significantly associated with
risk of dementia (all-cause dementia or Alzheimer disease). Among all
participants, higher levels of plasma total tau, examined as a continuous
variable, were associated with significant (P < .05) declines in global
cognition, memory, attention, and visuospatial ability over a median follow-up of
3.0 years (range, 1.1-4.9 years). In additional analyses restricting the follow
up to 15 months, plasma total tau did not predict decline among CN participants.
However, among participants with MCI, higher plasma total tau levels were
associated with greater decline in both visuospatial ability (regression
coefficient [b] = -0.50 [0.15], P < .001) and global cognition (b = -0.27 [0.10],
P = .009) at 15 months. Adjusting for elevated brain Abeta did not attenuate any
association. There was no interaction between plasma total tau level and brain
Abeta for prognosis with any outcome. Conclusions and Relevance: These results
suggest that elevated plasma total tau levels are associated with cognitive
decline, but the results differ based on cognitive status and the duration of
follow-up. The association between plasma total tau levels and cognition is
independent of elevated brain Abeta.
PMID- 28692711
TI - Mechanical Thrombectomy After Intravenous Thrombolysis vs Mechanical Thrombectomy
Alone in Acute Stroke.
PMID- 28692712
TI - Association Between Contemporary Trends in Inferior Vena Cava Filter Placement
and the 2010 US Food and Drug Administration Advisory.
PMID- 28692714
TI - Core Quality and Outcome Measures for Pediatric Health.
PMID- 28692713
TI - Value-Based Pricing and State Reform of Prescription Drug Costs.
PMID- 28692715
TI - Continued High Rates of IVC Filter Use After US Food and Drug Safety Warning.
PMID- 28692716
TI - Extending the Social Justice Call to Treatment Outcomes.
PMID- 28692717
TI - Medicare Advantage Reimbursement to Physicians.
PMID- 28692718
TI - Physician Reimbursement in Medicare Advantage Compared With Traditional Medicare
and Commercial Health Insurance.
AB - Importance: Nearly one-third of Medicare beneficiaries are enrolled in a Medicare
Advantage (MA) plan, yet little is known about the prices that MA plans pay for
physician services. Medicare Advantage insurers typically also sell commercial
plans, and the extent to which MA physician reimbursement reflects traditional
Medicare (TM) rates vs negotiated commercial prices is unclear. Objective: To
compare prices paid for physician and other health care services in MA,
traditional Medicare, and commercial plans. Design, Setting, and Participants:
Retrospective analysis of claims data evaluating MA prices paid to physicians and
for laboratory services and durable medical equipment between 2007 and 2012 in
348 US core-based statistical areas. The study population included all MA and
commercial enrollees with a large national health insurer operating in both
markets, as well as a 20% sample of TM beneficiaries. Exposures: Enrollment in an
MA plan. Main Outcomes and Measures: Mean reimbursement paid to physicians,
laboratories, and durable medical equipment suppliers for MA and commercial
enrollees relative to TM rates for 11 Healthcare Common Procedure Coding Systems
(HCPCS) codes spanning 7 sites of care. Results: The sample consisted of 144
million claims. Physician reimbursement in MA was more strongly tied to TM rates
than commercial prices, although MA plans tended to pay physicians less than TM.
For a mid-level office visit with an established patient (Current Procedural
Terminology [CPT] code 99213), the mean MA price was 96.9% (95% CI, 96.7%-97.2%)
of TM. Across the common physician services we evaluated, mean MA reimbursement
ranged from 91.3% of TM for cataract removal in an ambulatory surgery center (CPT
66984; 95% CI, 90.7%-91.9%) to 102.3% of TM for complex evaluation and management
of a patient in the emergency department (CPT 99285; 95% CI, 102.1%-102.6%).
However, for laboratory services and durable medical equipment, where commercial
prices are lower than TM rates, MA plans take advantage of these lower commercial
prices, ranging from 67.4% for a walker (HCPCS code E0143; 95% CI, 66.3%-68.5%)
to 75.8% for a complete blood cell count (CPT 85025; 95% CI, 75.0%-76.6%).
Conclusions and Relevance: Traditional Medicare's administratively set rates act
as a strong anchor for physician reimbursement in the MA market, although MA
plans succeed in negotiating lower prices for other health care services for
which TM overpays. Reforms that transition the Medicare program toward some
premium support models could substantially affect how physicians and other
clinicians are paid.
PMID- 28692720
TI - Mechanical Thrombectomy After Intravenous Thrombolysis vs Mechanical Thrombectomy
Alone in Acute Stroke-Reply.
PMID- 28692719
TI - Electrocardiograms in Low-Risk Patients Undergoing an Annual Health Examination.
AB - Importance: Clinical guidelines advise against routine electrocardiograms (ECG)
in low-risk, asymptomatic patients, but the frequency and impact of such ECGs are
unknown. Objective: To assess the frequency of ECGs following an annual health
examination (AHE) with a primary care physician among patients with no known
cardiac conditions or risk factors, to explore factors predictive of receiving an
ECG in this clinical scenario, and to compare downstream cardiac testing and
clinical outcomes in low-risk patients who did and did not receive an ECG after
their AHE. Design, Setting, and Participants: A population-based retrospective
cohort study using administrative health care databases from Ontario, Canada,
between 2010/2011 and 2014/2015 to identify low-risk primary care patients and to
assess the subsequent outcomes of interest in this time frame. All patients 18
years or older who had no prior cardiac medical history or risk factors who
received an AHE. Exposures: Receipt of an ECG within 30 days of an AHE. Main
Outcomes and Measures: Primary outcome was receipt of downstream cardiac testing
or consultation with a cardiologist. Secondary outcomes were death,
hospitalization, and revascularization at 12 months. Results: A total of 3 629
859 adult patients had at least 1 AHE between fiscal years 2010/2011 and
2014/2015. Of these patients, 21.5% had an ECG within 30 days after an AHE. The
proportion of patients receiving an ECG after an AHE varied from 1.8% to 76.1%
among 679 primary care practices (coefficient of quartile dispersion [CQD], 0.50)
and from 1.1% to 94.9% among 8036 primary care physicians (CQD, 0.54). Patients
who had an ECG were significantly more likely to receive additional cardiac
tests, visits, or procedures than those who did not (odds ratio [OR], 5.14; 95%
CI, 5.07-5.21; P < .001). The rates of death (0.19% vs 0.16%), cardiac-related
hospitalizations (0.46% vs 0.12%), and coronary revascularizations (0.20% vs
0.04%) were low in both the ECG and non-ECG cohorts. Conclusions and Relevance:
Despite recommendations to the contrary, ECG testing after an AHE is relatively
common, with significant variation among primary care physicians. Routine ECG
testing seems to increase risk for a subsequent cardiology testing and
consultation cascade, even though the overall cardiac event rate in both groups
was very low.
PMID- 28692721
TI - Extending the Social Justice Call to Treatment Outcomes-Reply.
PMID- 28692722
TI - Effective Dynamic Range and Retest Reliability of Dark-Adapted Two-Color Fundus
Controlled Perimetry in Patients With Macular Diseases.
AB - Purpose: To determine the effective dynamic range (EDR), retest reliability, and
number of discriminable steps (DS) for mesopic and dark-adapted two-color fundus
controlled perimetry (FCP) using the S-MAIA (Scotopic-Macular Integrity
Assessment) "micro-perimeter." Methods: In this prospective cross-sectional
study, each of the 52 eyes of 52 subjects with various macular diseases (mean age
62.0 +/- 16.9 years; range, 19.1-90.1 years) underwent duplicate mesopic
(achromatic stimuli, 400-800 nm), dark-adapted cyan (505 nm), and dark-adapted
red (627 nm) FCP using a grid of 61 stimuli covering 18 degrees of the central
retina. The EDR, the number of DS, and the retest reliability for point-wise
sensitivity (PWS) were analyzed. The effects of fixation stability, sensitivity,
and age on retest reliability were examined using mixed-effects models. Results:
The EDR was 10 to 30 dB with five DS for mesopic and 4 to 17 dB with four DS for
dark-adapted cyan and red testing. PWS retest reliability was good among all
three types of retinal sensitivity assessments (coefficient of repeatability +/
5.79, +/-4.72, and +/-4.77 dB, respectively) and did not depend on fixation
stability or age. PWS had no effect on retest variability in dark-adapted cyan
and dark-adapted red testing but had a minor effect in mesopic testing.
Conclusions: Combined mesopic and dark-adapted two-color FCP allows for reliable
topographic testing of cone and rod function in patients with various macular
diseases with and without foveal fixation. Retest reliability is homogeneous
across eccentricities and various degrees of scotoma depth, including zones at
risk for disease progression. These reliability estimates can serve for the
design of future clinical trials.
PMID- 28692723
TI - Safety of Converting From Tetrabenazine to Deutetrabenazine for the Treatment of
Chorea.
AB - Importance: Tetrabenazine is efficacious for chorea control; however,
tolerability concerns exist. Deutetrabenazine, a novel molecule that reduces
chorea, was well tolerated in a double-blind, placebo-controlled study.
Objectives: To evaluate the safety and explore the efficacy of conversion from
tetrabenazine to deutetrabenazine in patients with chorea associated with
Huntington disease (HD). Design, Setting, and Participants: In this ongoing, open
label, single-arm study that started on December 21, 2013, 37 patients at 13
Huntington Study Group sites in the United States and Australia who were taking
stable doses of tetrabenazine that provided a therapeutic benefit were switched
overnight to deutetrabenazine therapy. After week 1, the deutetrabenazine dose
was titrated on a weekly basis for optimal chorea control. Interventions:
Deutetrabenazine administration at a dosage thought to provide comparable
systemic exposure to the active metabolites of the prior, stable tetrabenazine
regimen. Main Outcomes and Measures: Safety measures included adverse events
(AEs), clinical laboratory tests, vital signs, electrocardiograms, and validated
scales. Changes in the Unified Huntington's Disease Rating Scale total maximal
chorea score and total motor score were efficacy end points. Results: Of the 53
patients with HD screened for the study, 37 ambulatory patients with manifest HD
(mean [SD] age, 52.4 [11.5] years; 22 [59%] male and 15 [41%] female; 36 white
[97.3%]) were enrolled. Deutetrabenazine was generally well tolerated, with low
rates of neuropsychiatric AEs. Safety scales did not reveal subclinical toxicity
with deutetrabenazine treatment. Rates of dose reduction or suspension
attributable to AEs were also low. Chorea control, as measured by the total
maximal chorea score, was maintained at week 1 and significantly improved at week
8 (mean [SD] change from baseline, 2.1 [3.2]; P < .001). Conclusions and
Relevance: In patients with chorea, overnight conversion to deutetrabenazine
therapy provided a favorable safety profile and effectively maintained chorea
control.
PMID- 28692724
TI - Toroidal sensor arrays for real-time photoacoustic imaging.
AB - This article addresses theoretical and numerical investigation of image formation
in photoacoustic (PA) imaging with complex-shaped concave sensor arrays. The
spatial resolution and the size of sensitivity region of PA and laser ultrasonic
(LU) imaging systems are assessed using sensitivity maps and spatial resolution
maps in the image plane. This paper also discusses the relationship between the
size of high-sensitivity regions and the spatial resolution of real-time imaging
systems utilizing toroidal arrays. It is shown that the use of arrays with
toroidal geometry significantly improves the diagnostic capabilities of PA and LU
imaging to investigate biological objects, rocks, and composite materials.
PMID- 28692725
TI - Visual speed sensitivity in the drum corps color guard.
AB - Drum corps color guard experts spend years developing skills in spinning rifles,
sabers, and flags. Their expertise provides a unique window into factors that
govern sensitivity to the speed of rotational and radial motion. Prior
neurophysiological research demonstrates that rotational and radial motion
register in the Medial Superior Temporal (MST) region of the primate visual
system. To the extent that shared neural events govern rotational and radial
speed sensitivity, one would expect expertise on either task to transfer to the
other. One similarly would expect shared neural events to generate correlations
between rotational and radial speed sensitivity. We evaluated these predictions
via visual speed sensitivity tests on drum corps color guard experts, drum corps
low brass experts, and other age-matched control participants. Displays comprised
bilaterally presented plaid patterns that rotated, radiated, or both.
Participants reported which side contained faster motion. The data revealed a
modest but reliably reproducible and specific group-by-task interaction; color
guard speed sensitivity exhibited a rotational motion advantage and radial motion
disadvantage. Additionally, rotational and radial speed sensitivity failed to
predict each other significantly. Overall, the findings match predictions that
follow from a dissociation between the neural events governing rotational and
radial speed sensitivity.
PMID- 28692728
TI - Effect of a Baby-Led Approach to Complementary Feeding on Infant Growth and
Overweight: A Randomized Clinical Trial.
AB - Importance: Baby-led approaches to complementary feeding, which promote self
feeding of all nonliquid foods are proposed to improve energy self-regulation and
lower obesity risk. However, to date, no randomized clinical trials have studied
this proposition. Objective: To determine whether a baby-led approach to
complementary feeding results in a lower body mass index (BMI) than traditional
spoon-feeding. Design, Setting, and Participants: The 2-year Baby-Led
Introduction to Solids (BLISS) randomized clinical trial recruited 206 women (168
[81.6%] of European ancestry; 85 [41.3%] primiparous) in late pregnancy from
December 19, 2012, through March 17, 2014, as part of a community intervention in
Dunedin, New Zealand. Women were randomized to a control condition (n = 101) or
the BLISS intervention (n = 105) after stratification for parity and education.
All outcomes were collected by staff blinded to group randomization, and no
participants withdrew because of an adverse event. Data were analyzed based on
intention to treat. Interventions: Mothers in the BLISS group received lactation
consultant support (>=5 contacts) to extend exclusive breastfeeding and delay
introduction of complementary foods until 6 months of age and 3 personalized face
to-face contacts (at 5.5, 7.0, and 9.0 months). Main Outcomes and Measures: The
primary outcome was BMI z score (at 12 and 24 months). Secondary outcomes
included energy self-regulation and eating behaviors assessed with questionnaires
at 6, 12, and 24 months and energy intake assessed with 3-day weighed diet
records at 7, 12, and 24 months. Results: Among the 206 participants (mean [SD]
age, 31.3 [5.6] years), 166 were available for analysis at 24 months (retention,
80.5%). The mean (SD) BMI z score was not significantly different at 12 months
(control group, 0.20 [0.89]; BLISS group, 0.44 [1.13]; adjusted difference, 0.21;
95% CI, -0.07 to 0.48) or at 24 months (control group, 0.24 [1.01]; BLISS group,
0.39 [1.04]; adjusted difference, 0.16; 95% CI, -0.13 to 0.45). At 24 months, 5
of 78 infants (6.4%) were overweight (BMI>=95th percentile) in the control group
compared with 9 of 87 (10.3%) in the BLISS group (relative risk, 1.8; 95% CI, 0.6
5.7). Lower satiety responsiveness was observed in BLISS infants at 24 months
(adjusted difference, -0.24; 95% CI, -0.41 to -0.07). Parents also reported less
food fussiness (adjusted difference, -0.33; 95% CI, -0.51 to -0.14) and greater
enjoyment of food (adjusted difference, 0.25; 95% CI, 0.07 to 0.43) at 12 months
in BLISS infants. Estimated differences in energy intake were 55 kJ (95% CI, -284
to 395 kJ) at 12 months and 143 kJ (95% CI, -241 to 526 kJ) at 24 months.
Conclusions and Relevance: A baby-led approach to complementary feeding did not
result in more appropriate BMI than traditional spoon-feeding, although children
were reported to have less food fussiness. Further research should determine
whether these findings apply to individuals using unmodified baby-led weaning.
Trial Registration: http://anzctr.org.au Identifier: ACTRN12612001133820.
PMID- 28692729
TI - Availability of Definitive Hospital Care for Children.
AB - Importance: Timely and efficient access to hospital care is essential for the
health and well-being of children. As insurance networks, accountable care
organizations, and alternative payment methods evolve, these new systems of care
must continue to serve the needs of children. Objective: To test the hypothesis
that the availability of definitive pediatric hospital care is significantly more
limited than adult care and is decreasing disproportionately. Design: This study
used case mix data during fiscal years 2004 through 2014 to measure transfer
frequency and identify the site of care completion for all patients seen in acute
care hospitals throughout Massachusetts. Patterns of care among children were
then compared with patterns of care among adults. Participants were all patients
seen in an emergency department or admitted to a hospital from 2004 through 2014,
including more than 34 million encounters. Main Outcomes and Measures: Hospital
Capability Index and Regionalization Index for all acute care hospitals and all
conditions within the Clinical Classifications Software of the Healthcare Cost
and Utilization Project. Results: Over the study period, the Commonwealth of
Massachusetts hospital system was composed of 66 acute care hospitals. After
excluding newborns and mental health conditions, there were 34 511 312
encounters, with 25 226 014 emergency department visits and 9 285 298 observation
or full admissions. From 2004 through 2014, care for adults and children
concentrated among hospitals but much more so for pediatric care. The number of
children requiring care in more than one hospital increased 36.2% (from 7190 to
9793). The median (interquartile range [IQR]) Hospital Capability Index,
reflecting the likelihood of a hospital completing a patient's care without
transfer, decreased 10.8% (from 0.74 [IQR, 0.65-0.81] to 0.66 [IQR, 0.53-0.76])
for adult care and 65.0% (0.20 [IQR, 0.05-0.34] to 0.07 [IQR, 0.01-0.23]) for
pediatric care. Almost all of the shift was from nonacademic to academic
hospitals. The median Regionalization Index, reflecting the degree to which care
for specific conditions is regionalized, was very high for pediatric conditions
and further increased from 0.79 (IQR, 0.67-0.91) to 0.87 (IQR, 0.80-0.91). Over
the same decade, the mean Regionalization Index for adult conditions was low and
increased modestly from 0.25 (IQR, 0.14-0.39) to 0.32 (IQR, 0.19-0.46). Among
pediatric conditions, more than 75% were highly regionalized in 2014 compared
with fewer than 50% in 2004. Conclusions and Relevance: Pediatric hospital care
has become increasingly concentrated, and many children with common conditions
are now less frequently treated in the community. This finding has significant
implications for systemwide capacity management and should be specifically
accounted for in public health activities, disaster planning, and determinations
of network adequacy.
PMID- 28692731
TI - Temporal Trends in the Numbers of Skilled Nursing Facility Specialists From 2007
Through 2014.
PMID- 28692730
TI - Secular Trends of Amyotrophic Lateral Sclerosis: The Piemonte and Valle d'Aosta
Register.
AB - Importance: This study reports the long-term epidemiologic trends of amyotrophic
lateral sclerosis (ALS) based on a prospective register. Objective: To examine
the 20-year epidemiologic trends of ALS in the Piemonte and Valle d'Aosta regions
of Italy. Design, Setting, and Participants: The Piemonte and Valle d'Aosta
Register for ALS (PARALS) is an epidemiologic prospective register that covers 2
Italian regions (population of 4 476 931 inhabitants according to the 2011
census) from January 1, 1995, through December 31, 2014. Case ascertainment is
based on multiple sources (neurologic departments, hospital discharge archives,
and mortality records). Incidence rates are age and sex standardized for the
Italian population of the 2011 census. Age-period-cohort (APC) analysis was
performed using a Poisson regression model. Main Outcomes and Measures: The
primary study outcomes were long-term incidence and prevalence rates of ALS using
a prospective design and their determinants. Results: During the study period, a
total of 2702 patients (mean [SD] age at onset, 65.7 [11.1] years; 1246 [46.1%]
female and 1456 [53.9%] male) received a diagnosis of ALS between 1995 and 2014,
corresponding to a crude annual incidence rate of 3.03 per 100 000 population
(95% CI, 2.85-3.23) and an adjusted incidence rate of 2.78 per 100 000 population
(95% CI, 2.57-2.96). The age-adjusted incidence rate increased in the 2 decades
of the study (1995-2004: 2.66; 95% CI, 2.50-2.83; 2005-2014: 2.89; 95% CI, 2.71
3.07; P = .04), mostly in women. The adjusted rate ratio of men to women
decreased from 1.27:1 (1995-2004) to 1.17:1 (2005-2014). The analysis of deviance
for the APC regression models indicated that the drift variable is relevant in
explaining the variation of ALS incidence rates over time in the overall
population (change in deviance, 4.6553; P = .03) and in women (change in
deviance, 3.8821; P = .05) but not in men (change in deviance, 0.77215; P = .38).
A total of 479 patients with ALS were alive and had not undergone tracheostomy at
the prevalence day (December 31, 2014), corresponding to a crude prevalence rate
of 10.54 per 100 000 population (95% CI, 9.64-11.52). Conclusions and Relevance:
During the 1995 to 2014 period, the crude and adjusted incidences of ALS
increased in Piemonte and Valle d'Aosta, mostly in women. The APC model revealed
that the increase of ALS incidence is attributable to a birth cohort effect in
women, with a peak in the 1930 cohort. The different increase of ALS incidence in
men and women points to an effect of exogenous factors with a differential effect
on the 2 sexes, acting on a genetic background.
PMID- 28692732
TI - Growth of Skilled Nursing Facility Specialists: Navigating Between What Is Ideal
and What Is Practical.
PMID- 28692733
TI - Shared Decision Making-The Importance of Diagnosing Preferences.
PMID- 28692734
TI - A National Survey of Medicaid Beneficiaries' Experiences and Satisfaction With
Health Care.
PMID- 28692735
TI - An Anti-VEGF-B Antibody Fragment Induces Regression of Pre-Existing Blood Vessels
in the Rat Cornea.
AB - Purpose: We tested the ability of an antibody fragment with specificity for
vascular endothelial growth factor-B (VEGF-B) to regress nascent and established
corneal blood vessels in the rat. Methods: A single chain variable antibody
fragment (scFv) with specificity for VEGF-B was engineered from the 2H10
hybridoma. Binding to rat, mouse, and human VEGF-B was confirmed by surface
plasmon resonance. Activity of the anti-VEGF-B scFv on developing and established
corneal blood vessels was assessed following unilateral superficial cautery in
male and female outbred Sprague Dawley rats. Groups (untreated, control scFv
treated, or anti-VEGF-B scFv-treated) comprised 6 to 22 rats. Treatment consisted
of 5 MUL scFv, 1 mg/mL, applied topically five times per day for 14 days, or two
subconjunctival injections, 50 MUg scFv each, applied 7 days apart, or combined
topical and subconjunctival treatment. Corneal vessel area was quantified on
hematoxylin-stained corneal flat-mounts, and groups were compared using the Mann
Whitney U test, with post hoc Bonferroni correction. Immunohistochemistry for
cleaved caspase-3 was performed. Results: Topical anti-VEGF-B scFv therapy alone
did not regress corneal blood vessels significantly (P > 0.05). Subconjunctival
injection and combined treatment regressed 14-day established corneal blood
vessels (25% reduction in vessel area [P = 0.04] and 37% reduction in vessel area
[P < 0.001], respectively, compared to results in untreated controls). Cleaved
caspase-3 was identified in vascular endothelial cells of anti-VEGF-B scFv
treated corneas. In scFv-treated rats, corneal endothelial cell function was
maintained to 12 weeks after treatment and a normal blink reflex was present.
Conclusions: The anti-VEGF-B scFv significantly regressed established but not
developing corneal blood vessels in rats.
PMID- 28692736
TI - Spatial Entropy Pursuit for Fast and Accurate Perimetry Testing.
AB - Purpose: To propose a static automated perimetry strategy that increases the
speed of visual field (VF) evaluation while retaining threshold estimate
accuracy. Methods: We propose a novel algorithm, spatial entropy pursuit (SEP),
which evaluates individual locations by using zippy estimation by sequential
testing (ZEST) but additionally uses neighboring locations to estimate the
sensitivity of related locations. We model the VF with a conditional random field
(CRF) where each node represents a location estimate that depends on itself as
well as its neighbors. Tested locations are randomly selected from a pool of
locations and new locations are added such that they maximally reduce the
uncertainty over the entire VF. When no location can further reduce the
uncertainty significantly, remaining locations are estimated from the CRF
directly. Results: SEP was evaluated and compared to tendency-oriented strategy,
ZEST, and the Dynamic Test Strategy by using computer simulations on a test set
of 245 healthy and 172 glaucomatous VFs. For glaucomatous VFs, root-mean-square
error (RMSE) of SEP was comparable to that of existing strategies (3.4 dB),
whereas the number of stimulus presentations of SEP was up to 23% lower than that
of other methods. For healthy VFs, SEP had an RMSE comparable to evaluated
methods (3.1 dB) but required 55% fewer stimulus presentations. Conclusions: When
compared to existing methods, SEP showed improved performances, especially with
respect to test speed. Thus, it represents an interesting alternative to existing
strategies.
PMID- 28692737
TI - An Ilomastat-CD Eye Drop Formulation to Treat Ocular Scarring.
AB - Purpose: The purpose of this study was to develop a topical matrix
metalloproteinase inhibitor preparation for antiscarring therapy. Methods: The
broad spectrum matrix metalloproteinase inhibitor ilomastat was formulated using
2-hydroxypropyl-beta-cyclodextrin in aqueous solution. In vitro activity of
ilomastat-cyclodextrin (ilomastat-CD) was examined using fibroblasts seeded in
collagen. Permeation of ilomastat-CD eye drop through pig eye conjunctiva was
confirmed using Franz diffusion cells. Ilomastat-CD eye drop was applied to
rabbit eyes in vivo, and the distribution of ilomastat in ocular tissues and
fluids was determined by liquid chromatography-mass spectroscopy. Results: The
aqueous solubility of ilomastat-CD was ~1000 MUg/mL in water and 1400 MUg/mL in
PBS (pH 7.4), which is greater than ilomastat alone (140 and 160 MUg/mL in water
and PBS, respectively). The in vitro activity of ilomastat-CD to inhibit collagen
contraction in the presence of human Tenon fibroblast cells was unchanged
compared to uncomplexed ilomastat. Topically administered ilomastat-CD in vivo to
rabbit eyes resulted in a therapeutic concentration of ilomastat being present in
the sclera and conjunctiva and within the aqueous humor. Conclusions: Ilomastat
CD has the potential to be formulated as an eye drop for use as an antifibrotic,
which may have implications for the prevention of scarring in many settings, for
example glaucoma filtration surgery.
PMID- 28692738
TI - Inhibition of Monocyte Chemoattractant Protein 1 Prevents Conjunctival Fibrosis
in an Experimental Model of Glaucoma Filtration Surgery.
AB - Purpose: To evaluate the effect of treatment with monocyte chemoattractant
protein-1 receptor inhibitor (MCP-Ri) to maintain bleb survival and prevent
fibrosis in an experimental model of glaucoma filtration surgery (GFS). Methods:
GFS was performed on one eye of C57/Bl6 mice (n = 36) that was treated with MCP
Ri, mitomycin-C (MMC), or vehicle at the time of surgery. Real-time polymerase
chain reaction was used to evaluate conjunctival expression of monocyte
chemoattractant protein-1 (MCP-1), TGFB1, TGFB2, collagen 1a1 (Col1a1), sparc
(Sparc), and fibronectin at 2 and 7 days following surgery. Anterior segment slit
lamp examination, optical coherence tomography, and confocal microscopy were
performed in vivo at day 14. Eyes were processed for immunohistochemical staining
of F4/80, a monocyte-macrophage marker, at day 2. In vitro experiments were also
performed to compare the effect of MMC, MCP-Ri, and vehicle on the viability of
mouse Tenon's fibroblasts. Results: Treatment with MCP-Ri results in a greater
reduction in the percentage of F4/80-positive cells in conjunctival blebs and
lesser MCP-1 gene expression following experimental GFS than MMC or control. Both
MMC and MCP-Ri reduced Col1a1 and Sparc expression, but not fibronectin. TGFB1
decreased with MCP-Ri but not MMC; MMC but not MCP-Ri reduced TGFB2. MMC and MCP
Ri treatment resulted in the preservation of bleb height at day 14, as compared
to control. MCP-Ri was less toxic to mouse Tenon's fibroblasts in comparison with
MMC. Conclusions: Targeting MCP-1 results in prolonged bleb survival following
experimental GFS with less cellular toxicity as compared to MMC. MCP inhibition
could provide a safer alternative to conventional antifibrotic adjunctive
treatments in GFS.
PMID- 28692739
TI - Analysis of Retinal Architectural Changes Using Intraoperative OCT Following
Surgical Manipulations With Membrane Flex Loop in the DISCOVER Study.
AB - Purpose: We investigate acute retinal alterations identified on intraoperative
optical coherence tomography (iOCT) immediately following surgical intervention
with the Finesse Flex Loop for vitreoretinal interface disorders. Methods: The
Determination of feasibility of Intraoperative Spectral domain microscope
Combined/integrated OCT Visualization during En face Retinal and ophthalmic
surgery (DISCOVER) study is a prospective multisurgeon intraoperative OCT
clinical study. Subjects who had participated in the DISCOVER study and had
undergone macular surgery with the membrane flex loop from August 2014 to July
2016 were identified. iOCT images and video sequences were evaluated at various
surgical time points. Subjects were excluded if iOCT images were not obtained
over the area of membrane peeling performed with the membrane flex loop.
Qualitative characteristics of intraoperative changes in retinal images were
analyzed, with particular focus on the retinal layers within the bed of membrane
peeling performed specifically with the membrane flex loop. Results: We studied
34 eyes of 34 patients, with a mean age of 72.7 (+/- 6.4) years, 25 of whom were
women. The intraoperative diagnosis was full thickness macular hole in 21 eyes
(62%) and epiretinal membrane in 13 (38%). All eyes had successful indocyanine
green-assisted inner limiting membrane (ILM) flap initiation using the membrane
loop. Intraoperative OCT demonstrated expansion of the ellipsoid zone-to-RPE
distance in 3 eyes (9%), definitive subretinal fluid accumulation in 1 eye (3%),
and hyperreflectivity of the inner retinal layers associated with retinal
hemorrhage in 10 eyes (29%). Retinal breaks were not observed in any eye.
Conclusions: Acute retinal alterations after ILM peeling with the membrane flex
loop were visualized at a frequency of less than 10%. Additional research is
needed to understand the clinical impact, if any, of these architectural
alterations.
PMID- 28692740
TI - Switching of alpha-Catenin From Epithelial to Neuronal Type During Lens
Epithelial Cell Differentiation.
AB - Purpose: Ocular lens fiber cell elongation, differentiation, and compaction are
associated with extensive reorganization of cell adhesive interactions and
cytoskeleton; however, our knowledge of proteins critical to these events is
still evolving. This study characterizes the distribution pattern of neuronal
specific alpha-catenin (alphaN-catenin) and its interaction with the N-cadherin
associated adherens junctions (AJs) and their stability in the mouse lens fibers.
Methods: Expression and distribution of alphaN-catenin in developing mouse and
adult human lenses was determined by RT-PCR, immunoblot, and immunofluorescence
analyses. Characterization of alphaN-catenin and N-cadherin interacting proteins
and colocalization analyses were performed using immunoprecipitation, mass
spectrometry, and confocal imaging. Effects of periaxin deficiency on the
stability of lens fiber cell AJs were evaluated using perixin-null mice. Results:
alphaN-catenin exhibits discrete distribution to lens fibers in both mouse and
human lenses, undergoing a robust up-regulation during fiber cell differentiation
and maturation. Epithelial-specific alpha-catenin (alphaE-catenin), in contrast,
distributes primarily to the lens epithelium. alphaN-catenin and N-cadherin
reciprocally coimmunoprecipitate and colocalize along with beta-catenin, actin,
spectrin, vinculin, Armadillo repeat protein deleted in velo-cardio-facial
syndrome homolog, periaxin, and ankyrin-B in lens fibers. Fiber cells from
periaxin-null mouse lenses revealed disrupted N-cadherin/alphaN-catenin-based
AJs. Conclusions: These results suggest that the discrete shift in alpha-catenin
expression from alphaE-catenin to alphaN-catenin subtype that occurs during lens
epithelial cell differentiation may play a key role in fiber cell
cytoarchitecture by regulating the assembly and stability of N-cadherin-based
AJs. This study also provides evidence for the importance of the fiber cell
specific cytoskeletal interacting periaxin, in the stability of N-cadherin/alphaN
catenin-based AJs in lens fibers.
PMID- 28692741
TI - Pulmonary embolism in a morbidly obese patient receiving dabigatran.
PMID- 28692742
TI - Vitamin K antagonists with or without long-term antiplatelet therapy in
outpatients with stable coronary artery disease and atrial fibrillation:
Association with ischemic and bleeding events.
AB - BACKGROUND: It remains uncertain whether patients with atrial fibrillation (AF)
requiring long-term oral anticoagulation (OAC) and with stable coronary artery
disease (CAD) should receive antiplatelet therapy (APT) in addition to OAC.
HYPOTHESIS: APT in addition to OAC would be more effective than OAC alone in
preventing ischaemic events in such patients. METHODS: In the international
REduction of Atherothrombosis for Continued Health (REACH) Registry including 68
236 outpatients with or at risk for atherothrombosis, we identified 2347 patients
with stable CAD and AF receiving vitamin K antagonists (VKA). Using propensity
score matching, patients treated with VKA (n = 1481) were compared with those
receiving VKA + APT at inclusion (n = 866). The primary outcome was major adverse
cardiovascular events (MACE) at 4 years (cardiovascular death, myocardial
infarction, or stroke). Secondary outcomes were all-cause death and bleeding
leading to hospitalization and transfusion. RESULTS: Patients receiving VKA only
were older (74 vs 72 years, P < 0.01), had less diabetes (37% vs 42%, P = 0.02),
and less frequent history of percutaneous coronary intervention (28.7% vs 43.9%,
P < 0.01). The mean CHA2 DS2 -VaSc score was 4.9 in the VKA group vs 4.7 in the
VKA + APT group (P < 0.01). After propensity score matching, the rate of MACE was
similar between groups: hazard ratio = 1.01 (0.77-1.33) (P = 0.94), whereas
bleeding tended to be more frequent in the VKA + APT group: odds ratio = 1.87
(0.99-3.50) (P = 0.051). CONCLUSIONS: In this observational analysis, the use of
APT in addition to OAC in patients with stable CAD and AF was not associated with
lower risk of ischemic events but possibly with higher bleeding rates. Randomized
trials are necessary to determine the optimal long-term antithrombotic strategy.
PMID- 28692743
TI - A flexible multivariate random effects proportional odds model with application
to adverse effects during radiation therapy.
AB - Radiation therapy in patients with head and neck cancer has a toxic effect on
mucosa, the soft tissue in and around the mouth. Hence mucositis is a serious
common side effect and is a condition characterized by pain and inflammation of
the surface of the mucosa. Although the mucosa recovers during breaks of and
following the radiotherapy course, the recovery will depend on the type of tissue
involved and on its location. We present a novel flexible multivariate random
effects proportional odds model that takes account of the longitudinal course of
oral mucositis at different mouth sites and of the radiation dosage (in terms of
cumulative dose). The model is an extension of the proportional odds model that
is used for ordinal response variables. Our model includes the ordinal
multivariate response of the mucositis score by site, random intercepts for
individuals, and a nonlinear function of cumulative radiation dose. The model
allows to test whether sensitivity differs by mouth sites after having adjusted
for site-specific cumulative radiation dose. The model also allows to check
whether and how the (nonlinear) effect of site-specific dose differs by site. We
fit the model to longitudinal patient data from a prospective observation and
find that after adjusting for cumulative dose, upper, lower lips, and mouth floor
are associated with the lowest mucositis scores and hard and soft palate are
associated with the highest mucositis scores. This implies the possibility that
tissues at different mouth sites differ in their sensitivity to the toxic effect
of radiation.
PMID- 28692744
TI - Graphene Composites with Cobalt Sulfide: Efficient Trifunctional Electrocatalysts
for Oxygen Reversible Catalysis and Hydrogen Production in the Same Electrolyte.
AB - Nitrogen and sulfur-codoped graphene composites with Co9 S8 (NS/rGO-Co) are
synthesized by facile thermal annealing of graphene oxides with cobalt nitrate
and thiourea in an ammonium atmosphere. Significantly, in 0.1 m KOH aqueous
solution the best sample exhibits an oxygen evolution reaction (OER) activity
that is superior to that of benchmark RuO2 catalysts, an oxygen reduction
reaction (ORR) activity that is comparable to that of commercial Pt/C, and an
overpotential of only -0.193 V to reach 10 mA cm-2 for hydrogen evolution
reaction (HER). With this single catalyst for oxygen reversible electrocatalysis,
a potential difference of only 0.700 V is observed in 0.1 m KOH solution between
the half-wave potential in ORR and the potential to reach 10 mA cm-2 in OER; in
addition, an overpotential of only 450 mV is needed to reach 10 mA cm-2 for full
water splitting in the same electrolyte. The present trifunctional catalytic
activities are markedly better than leading results reported in recent
literature, where the remarkable trifunctional activity is attributed to the
synergetic effects between N,S-codoped rGO, and Co9 S8 nanoparticles. These
results highlight the significance of deliberate structural engineering in the
preparation of multifunctional electrocatalysts for versatile electrochemical
reactions.
PMID- 28692745
TI - Decompression-Driven Superconductivity Enhancement in In2 Se3.
AB - An unexpected superconductivity enhancement is reported in decompressed In2 Se3 .
The onset of superconductivity in In2 Se3 occurs at 41.3 GPa with a critical
temperature (Tc ) of 3.7 K, peaking at 47.1 GPa. The striking observation shows
that this layered chalcogenide remains superconducting in decompression down to
10.7 GPa. More surprisingly, the highest Tc that occurs at lower decompression
pressures is 8.2 K, a twofold increase in the same crystal structure as in
compression. It is found that the evolution of Tc is driven by the pressure
induced R-3m to I-43d structural transition and significant softening of phonons
and gentle variation of carrier concentration combined in the pressure quench.
The novel decompression-induced superconductivity enhancement implies that it is
possible to maintain pressure-induced superconductivity at lower or even ambient
pressures with better superconducting performance.
PMID- 28692746
TI - Noncovalent Se...O Conformational Locks for Constructing High-Performing
Optoelectronic Conjugated Polymers.
AB - Noncovalent conformational locks are broadly employed to construct highly planar
pi-conjugated semiconductors exhibiting substantial charge transport
characteristics. However, current chalcogen-based conformational lock strategies
for organic semiconductors are limited to S...X (X = O, N, halide) weak
interactions. An easily accessible (minimal synthetic steps) and structurally
planar selenophene-based building block, 1,2-diethoxy-1,2-bisselenylvinylene
(DESVS), with novel Se...O noncovalent conformational locks is designed and
synthesized. DESVS unique properties are supported by density functional theory
computed electronic structures, single crystal structures, and experimental
lattice cohesion metrics. Based on this building block, a new class of stable,
structurally planar, and solution-processable conjugated polymers are synthesized
and implemented in organic thin-film transistors (TFT) and organic photovoltaic
(OPV) cells. DESVS-based polymers exhibit carrier mobilities in air as high as
1.49 cm2 V-1 s-1 (p-type) and 0.65 cm2 V-1 s-1 (n-type) in TFTs, and power
conversion efficiency >5% in OPV cells.
PMID- 28692747
TI - Controllable Synthesis of Atomically Thin Type-II Weyl Semimetal WTe2 Nanosheets:
An Advanced Electrode Material for All-Solid-State Flexible Supercapacitors.
AB - Compared with 2D S-based and Se-based transition metal dichalcogenides (TMDs), Te
based TMDs display much better electrical conductivities, which will be
beneficial to enhance the capacitances in supercapacitors. However, to date, the
reports about the applications of Te-based TMDs in supercapacitors are quite
rare. Herein, the first supercapacitor example of the Te-based TMD is reported:
the type-II Weyl semimetal 1Td WTe2 . It is demonstrated that single crystals of
1Td WTe2 can be exfoliated into the nanosheets with 2-7 layers by liquid-phase
exfoliation, which are assembled into air-stable films and further all-solid
state flexible supercapacitors. The resulting supercapacitors deliver a mass
capacitance of 221 F g-1 and a stack capacitance of 74 F cm-3 . Furthermore, they
also show excellent volumetric energy and power densities of 0.01 Wh cm-3 and
83.6 W cm-3 , respectively, superior to the commercial 4V/500 uAh Li thin-film
battery and the commercial 3V/300 uAh Al electrolytic capacitor, in association
with outstanding mechanical flexibility and superior cycling stability
(capacitance retention of ~91% after 5500 cycles). These results indicate that
the 1Td WTe2 nanosheet is a promising flexible electrode material for high
performance energy storage devices.
PMID- 28692748
TI - Organic Ferroelectric-Based 1T1T Random Access Memory Cell Employing a Common
Dielectric Layer Overcoming the Half-Selection Problem.
AB - Organic electronics based on poly(vinylidenefluoride/trifluoroethylene) (P(VDF
TrFE)) dielectric is facing great challenges in flexible circuits. As one
indispensable part of integrated circuits, there is an urgent demand for low-cost
and easy-fabrication nonvolatile memory devices. A breakthrough is made on a
novel ferroelectric random access memory cell (1T1T FeRAM cell) consisting of one
selection transistor and one ferroelectric memory transistor in order to overcome
the half-selection problem. Unlike complicated manufacturing using multiple
dielectrics, this system simplifies 1T1T FeRAM cell fabrication using one common
dielectric. To achieve this goal, a strategy for semiconductor/insulator (S/I)
interface modulation is put forward and applied to nonhysteretic selection
transistors with high performances for driving or addressing purposes. As a
result, high hole mobility of 3.81 cm2 V-1 s-1 (average) for 2,6
diphenylanthracene (DPA) and electron mobility of 0.124 cm2 V-1 s-1 (average) for
N,N'-1H,1H-perfluorobutyl dicyanoperylenecarboxydiimide (PDI-FCN2 ) are obtained
in selection transistors. In this work, we demonstrate this technology's
potential for organic ferroelectric-based pixelated memory module fabrication.
PMID- 28692749
TI - Pick-and-Place Assembly of Single Microtubules.
AB - Intracellular transport is affected by the filament network in the densely packed
cytoplasm. Biophysical studies focusing on intracellular transport based on
microtubule-kinesin system frequently use in vitro motility assays, which are
performed either on individual microtubules or on random (or simple) microtubule
networks. Assembling intricate networks with high flexibility requires the
manipulation of 25 nm diameter microtubules individually, which can be achieved
through the use of pick-and-place assembly. Although widely used to assemble tiny
objects, pick-and-place is not a common practice for the manipulation of
biological materials. Using the high-level handling capabilities of
microelectromechanical systems (MEMS) technology, tweezers are designed and
fabricated to pick and place single microtubule filaments. Repeated picking and
placing cycles provide a multilayered and multidirectional microtubule network
even for different surface topographies. On-demand assembly of microtubules forms
crossings at desired angles for biophysical studies as well as complex networks
that can be used as nanotransport systems.
PMID- 28692750
TI - Can we go beyond surrogates?
AB - Two years ago, data presented at the annual American Diabetes Association (ADA)
meeting in New Orleans showed a marked decrease in deaths, especially those due
to cardiovascular disease, with the use of empagliflozin. Two major questions
have been asked: (i) was the result a fluke; and (ii) was it a class effect, or
was it specific to the agent used? The hope that both questions would be answered
by a second study has been answered: the conclusions of EMPA-REG were not an
anomaly and it is a class effect, not one caused by a specific drug. Importantly,
do these studies require us to alter our algorithms for the treatment of type 2
diabetes? The CANagliflozin cardioVascular Assessment Study (CANVAS) was designed
similarly to EMPA-REG, enrolling individuals who either had known cardiac disease
or were at high risk for cardiac disease. In fact, CANVAS involved two stages,
CANVAS and CANVAS R, which can be analyzed together. There were 10 142 patients
in the combined trial followed for a mean of 3.6 years. The average age was 63.3
years, 35.8% were women, the mean duration of diabetes was 13.5 years, and 65.6%
had known cardiovascular disease. In EMPA-REG, 7020 patients were followed for
3.1 years, 28.5% were women, and all had established cardiovascular disease. The
primary endpoint of both studies was the composite of cardiovascular death, non
fatal myocardial infarction, and non-fatal stroke. In both studies, the
components of the composite endpoint were studied along with other endpoints,
including hospitalization for heart failure, all-cause mortality, and progression
of renal disease. The primary endpoint was identically positive for superiority
with hazard ratio of 0.86 for empagliflozin versus placebo and for canagliflozin
versus placebo. Some differences were observed: both death from cardiovascular
disease and all-cause mortality occurred significantly less frequently with
empagliflozin in EMPA-REG, but the 13% lower total and cardiovascular mortality
seen with canagliflozin in CANVAS was not statistically significant. Both studies
showed a lower likelihood of hospitalization for heart failure with the
intervention, even in patients without known heart failure at baseline,
suggesting either that that diagnosis is often missed or that de novo heart
failure may be prevented by these agents. Perhaps the strongest answer to the
initial two questions comes from the CVD-REAL Study. Rather than being a
randomized controlled clinical trial, that study analyzed medical claims, primary
care or hospital records, and national registries from the US, Norway, Denmark,
Sweden, Germany, and the UK, including 309 056 patients started on a sodium
glucose cotransporter 2 (SGLT2) inhibitor or on other glucose-lowering drugs
using a propensity score matching algorithm. Canagliflozin was used by 53% of
those receiving SGLT2 inhibitors, dapagliflozin was used by 42% and empagliflozin
was used by 5%; those using these agents had hazard ratios for hospitalization
for heart failure and for mortality of 0.61 and 0.49, respectively, with no
differences either by country or by drug. The interesting hypothesis that this
and the two controlled trials show the harm of alternative treatments of diabetes
rather than the benefit of SGLT2 inhibitors has not been confirmed by subset
analyses of drug use in the control groups. There are several potentially
important differences between the studies. Strokes increased with empagliflozin
in EMPA-REG (not statistically significant). There was a significantly increased
likelihood of lower extremity amputation in CANVAS, although these events may not
have been fully studied in EMPA-REG. Finally, the benefit of SGLT2 inhibitor
therapy were seen within 3 months in EMPA-REG, while not appearing as rapidly in
CANVAS. Furthermore, in neither study was there a reduction in non-fatal
myocardial infarction. These considerations suggest that the benefit of SGLT2
inhibitors is not due to improvement in the underlying atherosclerotic process.
It is likely that all SGLT2 inhibitors will receive an indication for secondary
prevention of heart failure; whether the agents should be used in primary
prevention is a much more difficult question, because it would require a very
large study of patients without heart disease. The introduction of HbA1c
measurements in the late 1970s radically and significantly improved our treatment
of diabetes. However, our treatment of diabetes is ultimately not to lower HbA1c,
but to prevent the complications of diabetes. Values of HbA1c are only a
surrogate measure of diabetes. Currently, there is little agreement on the
treatment algorithm for diabetes after metformin therapy. One may now argue that
an SGLT2 inhibitor should be the preferred second-line therapy.
PMID- 28692751
TI - Multilevel covariance regression with correlated random effects in the mean and
variance structure.
AB - Multivariate regression methods generally assume a constant covariance matrix for
the observations. In case a heteroscedastic model is needed, the parametric and
nonparametric covariance regression approaches can be restrictive in the
literature. We propose a multilevel regression model for the mean and covariance
structure, including random intercepts in both components and allowing for
correlation between them. The implied conditional covariance function can be
different across clusters as a result of the random effect in the variance
structure. In addition, allowing for correlation between the random intercepts in
the mean and covariance makes the model convenient for skewedly distributed
responses. Furthermore, it permits us to analyse directly the relation between
the mean response level and the variability in each cluster. Parameter estimation
is carried out via Gibbs sampling. We compare the performance of our model to
other covariance modelling approaches in a simulation study. Finally, the
proposed model is applied to the RN4CAST dataset to identify the variables that
impact burnout of nurses in Belgium.
PMID- 28692752
TI - High-Efficiency Nonfullerene Organic Solar Cells with a Parallel Tandem
Configuration.
AB - In this work, a highly efficient parallel connected tandem solar cell utilizing a
nonfullerene acceptor is demonstrated. Guided by optical simulation, each of the
active layer thicknesses of subcells are tuned to maximize its light trapping
without spending intense effort to match photocurrent. Interestingly, a strong
optical microcavity with dual oscillation centers is formed in a back subcell,
which further enhances light absorption. The parallel tandem device shows an
improved photon-to-electron response over the range between 450 and 800 nm, and a
high short-circuit current density (J SC ) of 17.92 mA cm-2 . In addition, the
subcells show high fill factors due to reduced recombination loss under diluted
light intensity. These merits enable an overall power conversion efficiency (PCE)
of >10% for this tandem cell, which represents a ~15% enhancement compared to the
optimal single-junction device. Further application of the designed parallel
tandem configuration to more efficient single-junction cells enable a PCE of
>11%, which is the highest efficiency among all parallel connected organic solar
cells (OSCs). This work stresses the importance of employing a parallel tandem
configuration for achieving efficient light harvesting in nonfullerene-based
OSCs. It provides a useful strategy for exploring the ultimate performance of
organic solar cells.
PMID- 28692753
TI - Decreased pulmonary arterial proportional pulse pressure is associated with
increased mortality in group 1 pulmonary hypertension.
AB - BACKGROUND: This study evaluated the utility of a novel index, pulmonary arterial
(PA) proportional pulse pressure (PAPP; range 0-1, defined as [PA systolic
pressure - PA diastolic pressure] / PA systolic pressure), in predicting
mortality in patients with World Health Organization group 1 pulmonary
hypertension (PH). HYPOTHESIS: Low PAPP is associated with increased 5-year
mortality independent of a validated contemporary risk-prediction equation
(Pulmonary Hypertension Connection [PHC] equation). METHODS: In a group of 262
patients in the National Institutes of Health Primary Pulmonary Hypertension (NIH
PPH) Registry, PAPP and the PHC risk equation were used to predict mortality
during 5 years of follow-up using Cox proportional hazards models. Kaplan-Meier
survival curves were used to compare mortality among PAPP quartiles, and
significance was tested using the log-rank test. RESULTS: Patients in the lowest
quartile (PAPP <=0.47) had a significantly higher 5-year mortality than did
patients in higher quartiles (log-rank P = 0.016). In a Cox model adjusted for
the PHC equation, PAPP remained significantly associated with 5-year mortality
(hazard ratio: 0.74 per 0.10 increase in PAPP, 95% confidence interval: 0.61
0.90). The chi2 statistic for the single PAPP covariate in this model was 8.8 (P
= 0.003), which compared favorably with the chi2 statistic of 15.2 (P < 0.0001)
for the multivariable PHC equation. CONCLUSIONS: PAPP, an index of ventricular
arterial coupling, is independently associated with survival in World Health
Organization group 1 PH. The use of this easily measurable index for guiding risk
stratification needs further investigation.
PMID- 28692754
TI - Rapid sensory profiling and hedonic rating of whole grain sorghum-cowpea
composite biscuits by low income consumers.
AB - BACKGROUND: The challenges of malnutrition and urbanization in Africa demand the
development of acceptable, affordable, nutritious complementary-type foods.
Biscuits (i.e. cookies; a popular snack) from whole grain staples are an option.
The present study aimed to relate check-all-that-applies (CATA) sensory profiles
of sorghum-cowpea composite biscuits compared to economic commercial refined
wheat biscuits with hedonic ratings by low income consumers. In addition, the
nutritional composition and protein quality, L* a* b* colour and texture of the
biscuits were determined. RESULTS: The CATA method is suitable for rapidly
determining which attributes consumers perceive in food products and relating
these to acceptability. Consumers preferred the lighter, more yellow wheat
biscuits with ginger, vanilla, sweet and cinnamon flavours compared to the
stronger flavours (sorghum, beany and nutty) and harder but brittle, grittier,
dry and rough textured sorghum or sorghum-cowpea biscuits. However, a substantial
proportion of consumers also liked the latter biscuits. The composite biscuits
had higher dietary fibre content and a similar protein quality to the standards.
CONCLUSIONS: Whole grain sorghum-cowpea biscuits could serve as acceptable value
added nutritious complementary snacks for consumers in sub-Saharan Africa. The
biscuits are simple to produce for the creation of viable small enterprises. (c)
2017 Society of Chemical Industry.
PMID- 28692755
TI - Enabling Flexible Heterostructures for Li-Ion Battery Anodes Based on Nanotube
and Liquid-Phase Exfoliated 2D Gallium Chalcogenide Nanosheet Colloidal
Solutions.
AB - 2D metal chalcogenide (MC) nanosheets (NS) have displayed high capacities as
lithium-ion battery (LiB) anodes. Nevertheless, their complicated synthesis
routes coupled with low electronic conductivity greatly limit them as promising
LiB electrode material. Here, this work reports a facile single-walled carbon
nanotube (SWCNT) percolating strategy for efficiently maximizing the
electrochemical performances of gallium chalcogenide (GaX, X = S or Se).
Multiscaled flexible GaX NS/SWCNT heterostructures with abundant voids for Li+
diffusion are fabricated by embedding the liquid-exfoliated GaX NS matrix within
a SWCNT-percolated network; the latter improves the electron transport and ion
diffusion kinetics as well as maintains the mechanical flexibility. Consequently,
high capacities (i.e., 838 mAh g-1 per gallium (II) sulfide (GaS) NS/SWCNT mass
and 1107 mAh g-1 per GaS mass; the latter is close to the theoretical value) and
good rate capabilities are achieved, which can be majorly attributed to the
alloying processes of disordered Ga formed after the first irreversible GaX
conversion reaction, as monitored by in situ X-ray diffraction. The presented
approach, colloidal solution processing of SWCNT and liquid-exfoliated MC NS to
produce flexible paper-based electrode, could be generalized for wearable energy
storage devices with promising performances.
PMID- 28692756
TI - Directional Solution Coating by the Chinese Brush: A Facile Approach to Improving
Molecular Alignment for High-Performance Polymer TFTs.
AB - Directional solution coating by the Chinese brush provides a facile approach to
fabricate highly oriented polymer thin films by finely controlling the wetting
and dewetting processes under directional stress. The biggest advantage of the
Chinese brush over the normal western brush is the freshly emergent hairs used,
whose unique tapered structure renders a dynamic balance of the liquid within the
brush by multiple forces when interacting with the liquid. Consequently, the
liquid is steadily held within the brush without any unexpected leakage, making
the liquid transfer proceed in a well-controllable manner. It is demonstrated
that the Chinese brush coating enables the crystallization of the polymer and the
self-assembly of conjugated backbones to proceed in a quasi-steady state via a
certain direction, which is attributed to the controllable receding of the three
phase contact line during the dewetting process by the multiple parallel freshly
emergent hairs. The as-prepared polymer thin films exhibit over six times higher
charge-carrier mobility compared to the spin-coated films, which therefore
provides a general approach for high-performance organic thin-film transistors.
PMID- 28692757
TI - 2D Frameworks of C2 N and C3 N as New Anode Materials for Lithium-Ion Batteries.
AB - Novel layered 2D frameworks (C3 N and C2 N-450) with well-defined crystal
structures are explored for use as anode materials in lithium-ion batteries
(LIBs) for the first time. As anode materials for LIBs, C3 N and C2 N-450 exhibit
unusual electrochemical characteristics. For example, C2 N-450 (and C3 N) display
high reversible capacities of 933.2 (383.3) and 40.1 (179.5) mAh g-1 at 0.1 and
10 C, respectively. Furthermore, C3 N shows a low hypothetical voltage (~0.15 V),
efficient operating voltage window with ~85% of full discharge capacity secured
at >0.45 V, and excellent cycling stability for more than 500 cycles. The
excellent electrochemical performance (especially of C3 N) can be attributed to
their inherent 2D polyaniline frameworks, which provide large net positive charge
densities, excellent structural stability, and enhanced electronic/ionic
conductivity. Stable solid state interface films also form on the surfaces of the
2D materials during the charge/discharge process. These 2D materials with
promising electrochemical performance should provide insights to guide the design
and development of their analogues for future energy applications.
PMID- 28692758
TI - Shape-Shifting Azo Dye Polymers: Towards Sunlight-Driven Molecular Devices.
AB - The development of stimuli-responsive polymers is among the key goals of modern
materials science. The structure and properties of such switchable materials can
be designed to be controlled via various stimuli, among which light is frequently
the most powerful trigger. Light is a gentle energy source that can target
materials remotely, and with extremely high spatial and temporal resolution
easily and cheaply. Reversible light-control over molecular mechanical properties
in particular has in recent years attracted great interest due to potential
applications as optical-to-mechanical conversion actuators and 'devices',
enabling 'molecular robotic machines'. In this review, some recent examples and
emerging trends in this exciting field of research are highlighted, covering a
wide variety of polymer hosts that contain azobenzene photo-reversible switches.
It is hoped that this review will help stimulate more interest towards the
development of light-reversible materials for energy harvesting and conversion,
and their successful incorporation into a wide variety of current and future high
tech applications in devices.
PMID- 28692759
TI - Sperm morphology: assessment, pathophysiology, clinical relevance, and state of
the art in 2017.
AB - For over 30 years, sperm morphology assessment has been one of the most common
tests in evaluation of fertility. This review examines the clinical relevance of
sperm morphology assessment in the diagnosis of infertility and in assisted
reproductive technology, as well as its analytical reliability. Publications on
the pathophysiology, the analytical reliability of the test and its clinical
relevance in diagnosis and in Assisted Reproductive Technology (ART) were
evaluated. This review compared and discussed study methodologies and results,
including patient characteristics, preparation, smear staining methods and
classification systems. The assessment of the percentage of some abnormalities
such as for example thin head, amorphous head, or bent or asymmetrical neck is of
little clinical use, and their pathophysiology is not well explained as most are
physiological traits. Some studies have highlighted correlations between the
percentage of normal forms and functional sperm abnormalities, as well as
correlations with ability to conceive in vivo and, in some situations, with the
success of intra-uterine insemination (IUI) or conventional IVF. However, except
in the case of some specific sperm defects (easy to detect with 99 or 100% of
spermatozoa affected) and which are often linked to genetic disorders
(globozoospermia, macrocephaly, decapitated sperm syndrome and fibrous sheath
dysplasia), sperm morphology assessment has very poor sensitivity and specificity
in the diagnosis of infertility. Moreover, there is very little evidence that
indices of multiple sperm defects [sperm deformity index (SDI), teratozoospermia
index (TZI), and multiple abnormalities index (MAI)] are relevant. Above all,
many publications report a major lack of analytical reliability of this test,
mainly in assessment of the details of sperm abnormalities. Many questions arise
concerning how and when sperm morphology should be assessed, and how to interpret
the thresholds of normal forms. Questions are raised on the real clinical impact
of this test.
PMID- 28692760
TI - Current trends in admissions and outcomes of cardiac diseases in Ghana.
AB - Cardiovascular diseases (CVDs) pose a major burden in Africa, but data on
temporal trends in disease burden are lacking. We assessed trends in CVD
admissions and outcomes in central Ghana using a retrospective analysis of data
from January 2004 to December 2015 among patients admitted to the medical wards
of a tertiary medical center in Kumasi, Ghana. Rates of admissions and mortality
were expressed as CVD admissions and deaths divided by the total number of
medical admissions and deaths, respectively. Case fatality rates per specific
cardiac disease diagnosis were also computed. Over the period, there were 4226
CVD admissions, with a male-to-female ratio of 1.1 to 1. There was a progressive
increase in percentage of CVD admissions from 4.6% to 8.2%, representing an 78%
increase, between 2004 and 2014. Of the 2170 CVD cases whose data were available,
the top 3 causes of CVD admissions were heart failure (HF; 88.3%), ischemic heart
disease (IHD; 7.2%), and dysrhythmias (1.9%). Of all HF admissions, 52% were
associated with hypertension. IHD prevalence rose by 250% between 2005 and 2015.
There were 976 deaths (23%), with an increase in percentage of hospital deaths
that were cardiovascular in nature from 3.6% to 7.3% between 2004 and 2014,
representing a 102% increase. Cardiac disease admissions and mortality have
increased progressively over the past decade, with HF as the most common cause of
admission. Once rare, IHD is emerging as a significant contributor to the CVD
burden in sub-Saharan Africa.
PMID- 28692761
TI - Reply.
PMID- 28692762
TI - Nanoscale Ultrasound-Switchable FRET-Based Liposomes for Near-Infrared
Fluorescence Imaging in Optically Turbid Media.
AB - A new approach for fluorescence imaging in optically turbid media centered on the
use of nanoscale ultrasound-switchable FRET-based liposome contrast agents is
reported. Liposomes containing lipophilic carbocyanine dyes as FRET pairs with
emission wavelengths located in the near-infrared window are prepared. The
efficacy of FRET and self-quenching for liposomes with a range of fluorophore
concentrations is first calculated from measurement of the liposome emission
spectra. Exposure of the liposomes to ultrasound results in changes in the
detected fluorescent signal, the nature of which depends on the fluorophores
used, detection wavelength, and the fluorophore concentration. Line scanning of a
tube containing the contrast agents with 1 mm inner diameter buried at a depth of
1 cm in a heavily scattering tissue phantom demonstrates an improvement in image
spatial resolution by a factor of 6.3 as compared with images obtained in the
absence of ultrasound. Improvements are also seen in image contrast with the
highest obtained being 9% for a liposome system containing FRET pairs. Overall
the results obtained provide evidence of the potential the nanoscale ultrasound
switchable FRET-based liposomes studied here have for in vivo fluorescence
imaging.
PMID- 28692763
TI - Oriented Arrangement: The Origin of Versatility for Porous Graphene Materials.
AB - Macroscopic porous graphene materials composed of graphene sheets have
demonstrated their advantageous aspects in diverse application areas. It is
essential to maximize their excellent performances by rationally controlling the
sheet arrangement and pore structure. Bulk porous graphene materials with
oriented pore structure and arrangement of graphene sheets are prepared by
marrying electrolyte-assisted self-assembly and shear-force-induced alignment of
graphene oxide sheets, and the super elasticity and anisotropic mechanical,
electrical, and thermal properties induced by this unique structure are
systematically investigated. Its application in pressure sensing exhibits
ultrahigh sensitivity of 313.23 kPa-1 for detecting ultralow pressure variation
below 0.5 kPa, and it shows high retention rate for continuously intercepting dye
molecules with a high flux of ~18.7 L m-2 h-1 bar-1 and a dynamic removal rate of
510 mg m-2 h-1 .
PMID- 28692764
TI - Highly Efficient Perovskite-Perovskite Tandem Solar Cells Reaching 80% of the
Theoretical Limit in Photovoltage.
AB - Organic-inorganic hybrid perovskite multijunction solar cells have immense
potential to realize power conversion efficiencies (PCEs) beyond the Shockley
Queisser limit of single-junction solar cells; however, they are limited by large
nonideal photovoltage loss (V oc,loss ) in small- and large-bandgap subcells.
Here, an integrated approach is utilized to improve the V oc of subcells with
optimized bandgaps and fabricate perovskite-perovskite tandem solar cells with
small V oc,loss . A fullerene variant, Indene-C60 bis-adduct, is used to achieve
optimized interfacial contact in a small-bandgap (~1.2 eV) subcell, which
facilitates higher quasi-Fermi level splitting, reduces nonradiative
recombination, alleviates hysteresis instabilities, and improves V oc to 0.84 V.
Compositional engineering of large-bandgap (~1.8 eV) perovskite is employed to
realize a subcell with a transparent top electrode and photostabilized V oc of
1.22 V. The resultant monolithic perovskite-perovskite tandem solar cell shows a
high V oc of 1.98 V (approaching 80% of the theoretical limit) and a stabilized
PCE of 18.5%. The significantly minimized nonideal V oc,loss is better than state
of-the-art silicon-perovskite tandem solar cells, which highlights the prospects
of using perovskite-perovskite tandems for solar-energy generation. It also
unlocks opportunities for solar water splitting using hybrid perovskites with
solar-to-hydrogen efficiencies beyond 15%.
PMID- 28692765
TI - Highly Sensitive MoS2 Humidity Sensors Array for Noncontact Sensation.
AB - Recently, 2D materials exhibit great potential for humidity sensing applications
due to the fact that almost all atoms are at the surface. Therefore, the quality
of the material surface becomes the key point for sensitive perception. This
study reports an integrated, highly sensitive humidity sensors array based on
large-area, uniform single-layer molybdenum disulfide with an ultraclean surface.
Device mobilities and on/off ratios decrease linearly with the relative humidity
varying from 0% to 35%, leading to a high sensitivity of more than 104 . The
reversible water physisorption process leads to short response and decay times.
In addition, the device array on a flexible substrate shows stable performance,
suggesting great potential in future noncontact interface localization
applications.
PMID- 28692766
TI - Vertically Oriented 2D Layered Perovskite Solar Cells with Enhanced Efficiency
and Good Stability.
AB - Vertically oriented highly crystalline 2D layered (BA)2 (MA)n-1 Pbn I3n+1 (BA =
CH3 (CH2 )3 NH3 , MA = CH3 NH3 , n = 3, 4) perovskite thin-films are fabricated
with the aid of ammonium thiocyanate (NH4 SCN) additive through one-step spin
coating process. The humidity-stability of the film is certified by the almost
unchanged X-ray diffraction patterns after exposed to humid atmosphere (Hr = 55
+/- 5%) for 40 d. The photovoltaic devices with the structure of indium tin
oxide(ITO)/poly(3,4-ethylenedioxythiophene):poly(styrene-sulfonate)/(BA)2 (MA)n-1
Pbn I3n+1 (n = 3,4)/[6,6]-phenyl-C61 -butyric acid methyl ester/Bathocuproine/Ag
are fabricated. The devices based on (BA)2 (MA)2 Pb3 I10 perovskite (n = 3) with
the precursor composition of BAI:methylammonium iodide:PbI2 :NH4 SCN = 2:2:3:1
(by molar ratio) show an averaged power conversion efficiency (PCE) of 6.82%. In
the case of (BA)2 (MA)3 Pb4 I13 (n = 4), a higher PCE of 8.79% is achieved. Both
of the unsealed devices perform unique stability with almost unchanged PCE during
the period of storage in purified N2 glove box. This work provides a simple and
effective method to enhance the efficiency of the 2D perovskite solar cell.
PMID- 28692767
TI - Reactive Oxygen Species-Regulating Polymersome as an Antiviral Agent against
Influenza Virus.
AB - Reactive oxygen species (ROS) produced during mitochondrial oxidative
phosphorylation play an important role as signal messengers in the immune system
and also regulate signal transduction. ROS production, initiated as a consequence
of microbial invasion, if generated at high levels, induces activation of the MEK
(mitogen-activated protein kinase kinase)/ERK (extracellular signal-regulated
kinase) pathway to promote cell survival and proliferation. However, viruses
hijack the host cells' pathways, causing biphasic activation of the MEK/ERK
cascade. Thus, regulation of ROS leads to concomitant inhibition of virus
replication. In the present study, poly(aniline-co-pyrrole) polymerized
nanoregulators (PASomes) to regulate intracellular ROS levels are synthesized,
exploiting their oxidizing-reducing characteristics. Poly(aniline-co-pyrrole)
embedded within an amphiphilic methoxy polyethylene glycol-block
polyphenylalanine copolymer (mPEG-b-pPhe) are used. It is demonstrated that the
PASomes are water soluble, biocompatible, and could control ROS levels
successfully in vitro, inhibiting viral replication and cell death. Furthermore,
the effects of homopolymerized nanoregulators (polypyrrole assembled with mPEG-b
pPhe or polyaniline assembled with mPEG-b-pPhe) are compared with those of the
PASomes. Consequently, it is confirmed that the PASomes can regulate
intracellular ROS levels successfully and suppress viral infection, thereby
increasing the cell survival rate.
PMID- 28692768
TI - Cucurbit[7]uril: an emerging candidate for pharmaceutical excipients.
AB - Cucurbit[7]uril (CB[7]), belonging to the cucurbit[n]uril family (CB[n], n = 5-8,
10, or 13-15), may form host-guest complexes with a variety of small molecules of
biomedical interest. The physical and chemical properties of the complexed drugs
are often improved as a result of this complexation, suggesting the potential
application of CB[7] as a pharmaceutical excipient. This review has summarized
the most recent research progress reported between 2011 and early 2017 regarding
the biocompatibility of CB[7] and the influence of CB[7] on the stability,
solubility, biouptake, and biological activities (including therapeutic
efficacies and toxicities) of guest drug molecules. Through this systemic summary
and analysis, we intend to stimulate further research efforts in this area and
promote the use of CB[7] as an emerging pharmaceutical excipient to improve
various properties of drug molecules (or active pharmaceutical ingredients).
PMID- 28692769
TI - Enhancing the Performance of Perovskite Solar Cells by Hybridizing SnS Quantum
Dots with CH3 NH3 PbI3.
AB - The combination of perovskite solar cells and quantum dot solar cells has
significant potential due to the complementary nature of the two constituent
materials. In this study, solar cells (SCs) with a hybrid CH3 NH3 PbI3 /SnS
quantum dots (QDs) absorber layer are fabricated by a facile and universal in
situ crystallization method, enabling easy embedding of the QDs in perovskite
layer. Compared with SCs based on CH3 NH3 PbI3 , SCs using CH3 NH3 PbI3 /SnS QDs
hybrid films as absorber achieves a 25% enhancement in efficiency, giving rise to
an efficiency of 16.8%. The performance improvement can be attributed to the
improved crystallinity of the absorber, enhanced photo-induced carriers'
separation and transport within the absorber layer, and improved incident light
utilization. The generality of the methods used in this work paves a universal
pathway for preparing other perovskite/QDs hybrid materials and the synthesis of
entire nontoxic perovskite/QDs hybrid structure.
PMID- 28692770
TI - Impact of Stopping Tumor Necrosis Factor Inhibitors on Rheumatoid Arthritis
Patients' Burden of Disease.
AB - OBJECTIVE: To determine the impact of stopping tumor necrosis factor inhibitor
(TNFi) treatment on patient-reported outcomes (PROs) of physical and mental
health status, health utility, pain, disability, and fatigue in patients with
established rheumatoid arthritis (RA). METHODS: In the pragmatic, 12-month POET
trial, 817 RA patients with >=6 months of remission or stable low disease
activity were randomized 2:1 to stopping or continuing TNFi. In case of flare,
TNFi was restarted at the discretion of the rheumatologist. PROs were assessed
every 3 months. RESULTS: TNFi was restarted within 12 months in 252 of 531
patients (47.5%) in the stop group. At 3 months, mean PRO scores were
significantly worse in the stop group, and a larger proportion of patients
experienced a minimum clinically important difference (MCID) on all PROs. Effect
sizes (ES) were strongest for health utility (ES -0.24) and pain (ES -0.30). Mean
scores improved again after this point, but disability scores remained
significantly different at 12 months. After 12 months, the relative risk of
experiencing an MCID ranged from 1.16 for mental health status to 1.58 for
fatigue. Mean PRO scores for patients restarting TNFi within 6 months were no
longer significantly different from those that did not restart TNFi at 12 months.
CONCLUSION: Stopping TNFi had a significant negative short-term impact on a broad
range of PROs. Long-term negative consequences appeared to be limited, and
outcomes in patients needing to restart TNFi within the first 6 months tended to
be restored at 12 months.
PMID- 28692771
TI - Underlying Mechanisms of Adult-Onset Asthma and Periocular Xanthogranuloma:
Comment on the Article by Gallo et al.
PMID- 28692772
TI - Controlling Structural Anisotropy of Anisotropic 2D Layers in Pseudo-1D/2D
Material Heterojunctions.
AB - Chemical vapor deposition and growth dynamics of highly anisotropic 2D lateral
heterojunctions between pseudo-1D ReS2 and isotropic WS2 monolayers are reported
for the first time. Constituent ReS2 and WS2 layers have vastly different atomic
structure, crystallizing in anisotropic 1T' and isotropic 2H phases,
respectively. Through high-resolution scanning transmission electron microscopy,
electron energy loss spectroscopy, and angle-resolved Raman spectroscopy, this
study is able to provide the very first atomic look at intimate interfaces
between these dissimilar 2D materials. Surprisingly, the results reveal that ReS2
lateral heterojunctions to WS2 produce well-oriented (highly anisotropic) Re
chains perpendicular to WS2 edges. When vertically stacked, Re-chains orient
themselves along the WS2 zigzag direction, and consequently, Re-chains exhibit
six-fold rotation, resulting in loss of macroscopic scale anisotropy. The degree
of anisotropy of ReS2 on WS2 largely depends on the domain size, and decreases
for increasing domain size due to randomization of Re-chains and formation of
ReS2 subdomains. Present work establishes the growth dynamics of atomic junctions
between novel anisotropic/isotropic 2D materials, and overall results mark the
very first demonstration of control over anisotropy direction, which is a
significant leap forward for large-scale nanomanufacturing of anisotropic
systems.
PMID- 28692773
TI - Switching Colloidal Superstructures by Critical Casimir Forces.
AB - Recent breakthroughs in colloidal synthesis promise the bottom-up assembly of
superstructures on nano- and micrometer length scales, offering molecular
analogues on the colloidal scale. However, a structural control similar to that
in supramolecular chemistry remains very challenging. Here, colloidal
superstructures are built and controlled using critical Casimir forces on patchy
colloidal particles. These solvent-mediated forces offer direct analogues of
molecular bonds, allowing patch-to-patch binding with exquisite temperature
control of bond strength and stiffness. Particles with two patches are shown to
form linear chains undergoing morphological changes with temperature, resembling
a polymer collapse under poor-solvent conditions. This reversible temperature
switching carries over to particles with higher valency, exhibiting a variety of
patch-to-patch bonded structures. Using Monte Carlo simulations, it is shown that
the collapse results from the growing interaction range favoring close-packed
configurations. These results offer new opportunities for the active control of
complex structures at the nano and micrometer scale, paving the way to novel
temperature-switchable materials.
PMID- 28692774
TI - Developing and Refining New Candidate Criteria for Systemic Lupus Erythematosus
Classification: An International Collaboration.
AB - OBJECTIVE: To define candidate criteria within multiphase development of systemic
lupus erythematosus (SLE) classification criteria, jointly supported by the
American College of Rheumatology and the European League Against Rheumatism.
Prior steps included item generation and reduction by Delphi exercise, further
narrowed to 21 items in a nominal group technique exercise. Our objectives were
to apply an evidence-based approach to the 21 candidate criteria, and to develop
hierarchical organization of criteria within domains. METHODS: A literature
review identified the sensitivity and specificity of the 21 candidate criteria.
Data on the performance of antinuclear antibody (ANA) as an entry criterion and
operating characteristics of the candidate criteria in early SLE patients were
evaluated. Candidate criteria were hierarchically organized into clinical and
immunologic domains, and definitions were refined in an iterative process.
RESULTS: Based on the data, consensus was reached to use a positive ANA of >=1:80
titer (HEp-2 cells immunofluorescence) as an entry criterion and to have 7
clinical and 3 immunologic domains, with hierarchical organization of criteria
within domains. Definitions of the candidate criteria were specified. CONCLUSION:
Using a data-driven process, consensus was reached on new, refined criteria
definitions and organization based on operating characteristics. This work will
be followed by a multicriteria decision analysis exercise to weight criteria and
to identify a threshold score for classification on a continuous probability
scale.
PMID- 28692775
TI - Yolk-Shelled C@Fe3 O4 Nanoboxes as Efficient Sulfur Hosts for High-Performance
Lithium-Sulfur Batteries.
AB - Owing to the high theoretical specific capacity (1675 mA h g-1 ) and low cost,
lithium-sulfur (Li-S) batteries offer advantages for next-generation energy
storage. However, the polysulfide dissolution and low electronic conductivity of
sulfur cathodes limit the practical application of Li-S batteries. To address
such issues, well-designed yolk-shelled carbon@Fe3 O4 (YSC@Fe3 O4 ) nanoboxes as
highly efficient sulfur hosts for Li-S batteries are reported here. With both
physical entrapment by carbon shells and strong chemical interaction with Fe3 O4
cores, this unique architecture immobilizes the active material and inhibits
diffusion of the polysulfide intermediates. Moreover, due to their high
conductivity, the carbon shells and the polar Fe3 O4 cores facilitate fast
electron/ion transport and promote continuous reactivation of the active material
during the charge/discharge process, resulting in improved electrochemical
utilization and reversibility. With these merits, the S/YSC@Fe3 O4 cathodes
support high sulfur content (80 wt%) and loading (5.5 mg cm-2 ) and deliver high
specific capacity, excellent rate capacity, and long cycling stability. This work
provides a new perspective to design a carbon/metal-oxide-based yolk-shelled
framework as a high sulfur-loading host for advanced Li-S batteries with superior
electrochemical properties.
PMID- 28692776
TI - Preparation of Carbon-Rich g-C3 N4 Nanosheets with Enhanced Visible Light
Utilization for Efficient Photocatalytic Hydrogen Production.
AB - Exfoliation of layered bulk g-C3 N4 (CNB) to thin g-C3 N4 sheets in nanodomains
has attracted much attention in photocatalysis because of the intriguing
properties of nanoscaled g-C3 N4 . This study shows that carbon-rich g-C3 N4
nanosheets (CNSC) can be easily prepared by self-modification of polymeric melon
units through successively thermally treating bulk g-C3 N4 in an air and N2
atmosphere. The prepared CNSC not only retain the outstanding properties of
nanosheets, such as large surface area, high aspect ratios, and short charges
diffusion distance, but also overcome the drawback of enlarged bandgap caused by
the quantum size effect, resulting in an enhanced utilization of visible light
and photoinduced electron delocalization ability. Therefore, the as-prepared CNSC
show a high hydrogen evolution rate of 39.6 umol h-1 with a turnover number of
24.98 in 1 h at lambda > 400 nm. Under irradiation by longer wavelength of light
(lambda > 420 nm), CNSC still exhibit a superior hydrogen evolution rate, which
is 72.9 and 5.4 times higher than that of bulk g-C3 N4 and g-C3 N4 nanosheets,
respectively.
PMID- 28692777
TI - Simultaneous flow cytometric analysis of megakaryocyte polyploidy and a labile
intracellular protein using zinc-based fixation.
AB - Differentiating megakaryocytes undergo a unique endomitotic cell cycle leading to
large polyploidal cells, which fragment to generate platelets, blood cells
important for normal hemostasis. Simultaneous assessment of DNA content and
cellular proteins by flow cytometry is a useful tool to study megakaryocyte
differentiation and to define expression of proteins important for megakaryocyte
development and platelet formation. The usefulness of zinc salt-based fixation
(ZBF), a non-crosslinking method of cell fixation that permits downstream
analysis of nucleic acids (Jensen et al., Cytometry A 2010;77A:798-804), in flow
cytometric analysis of megakaryocyte ploidy in conjunction with extracellular and
intracellular proteins was assessed. ZBF of a megakaryocyte-like cell line
resulted in preservation of proteins similar to paraformaldehyde fixation, and
preservation of DNA content in a manner similar to methanol fixation. This is
highlighted by experiments in which polyploidal megakaryocytes were analyzed
simultaneously for endocytosis of a fluorescently-labeled, endocytosed labile
protein or expression of a cell surface integrin and DNA content. These studies
demonstrate that ZBF will be a valuable tool to study the molecular events
leading to platelet formation. (c) 2017 International Society for Advancement of
Cytometry.
PMID- 28692778
TI - Monolayer Tungsten Disulfide (WS2 ) via Chlorine-Driven Chemical Vapor Transport.
AB - Large-scale production of high-quality tungsten disulfide (WS2 ) monolayers is a
prerequisite for potential device applications using this promising transition
metal dichalcogenide semiconductor. The most researched technique is chemical
vapor deposition, typically involving the reaction of sulfur vapors with tungsten
oxide. Other techniques such as physical vapor deposition have been explored with
some success, but low vapor pressures make growth difficult. This study
demonstrates a growth process that relies on halide-driven vapor transport
commonly utilized in bulk crystal growth. Using a small amount of sodium chloride
salt as a source of chlorine, nonvolatile WS2 can react to form gaseous tungsten
chloride and sulfur. With an open tube system, a controlled reaction generates
mono and few-layer WS2 crystals. Optical and physical characterization of the
monolayer material shows good uniformity and triangular domains over 50 um in
length. Photoluminescence transient measurements show similar nonlinear exciton
dynamics as exfoliated flakes, attributed to multiparticle physics. Requiring
only the powder of the desired crystal and appropriate halide salt as precursors,
the technique has the potential to realize other layered materials that are
challenging to grow with current processes.
PMID- 28692779
TI - Why Do I Do Research? Why Should You Do Research?
PMID- 28692780
TI - The Experience of Parenting a Child With Disability in Old Age.
AB - BACKGROUND: There are growing numbers of older parents providing ongoing care for
adults with disabilities. A parent's aging calls for a redefinition of parental
care practices and roles in light of his or her own changing needs. PURPOSE: The
current study aims to highlight the ways in which aging parents perceive and
construct their parental role to adult children with disabilities at this point
in their lives. METHODS: An interpretive phenomenological analysis perspective
was used. Data collection was performed through in-depth, semistructured
interviews with 20 aging parents of children with developmental disabilities,
followed by a content analysis. RESULTS: Four patterns of parental identity
emerged: "Being happy is his responsibility; I did my part," embracing aging
needs; "I can do part-time worrying," a gradual letting go of parental roles;
"I'm worn out, but I keep going. What choice do I have?" bearing the brunt; "I'm
an old woman changing diapers," full-time parents. CONCLUSIONS: The findings
enable a deeper understanding of the various ways in which parents cope with
aging alongside caring for an adult child with disability. Hence, this study can
serve as a framework for developing tailored and differential intervention
methods for these families. CLINICAL RELEVANCE: As the world's people experience
longer life expectancy, of both individuals with disabilities and their parents,
nurses' education and practice should be challenged by the double sensitivities
of elder's caregiving and address the unique needs of this unique population.
PMID- 28692781
TI - Depression as a Risk Factor of Organic Diseases:An International Integrative
Review.
AB - PURPOSE AND DESIGN: This integrative review offers a systematic synthesis of the
international literature regarding the role of depression as a risk factor in
physical illnesses and the mechanisms of this connection. Special attention is
paid to those modifiable factors. FINDINGS: Published studies of depression and
physical illness and disease(N = 24) from five countries that were indexed in
PubMed, the Cumulative Index to Nursing and Allied Health Literature (CINAHL),
APA PsycNET, Scopus, Dialnet, and CUIDEN were examined. Results suggest that
depression is a significant risk factor for the development of physical illnesses
and diseases. More commonly studied were the connections between depression and
cardiovascular disease, metabolic syndrome, biochemical alterations, diabetes,
dementia, cognitive impairment, Alzheimer's disease, somatization and chronic
pain, asthma, arthritis, and hyperlipidemia. Less frequently studied conditions
connected to depression were cancer, infections, allergies, autoimmune disease,
gastric ulcer, rhinitis, thyroiditis, bronchitis, migraines, fractures, and
osteoporosis. CONCLUSIONS: Mechanisms connecting depression to physical illness
appear to involve alterations in the hypothalamic-pituitary axis, unhealthy
lifestyle, chronic or acute stressors including posttraumatic stress, an increase
in C-reactive protein (CRP) in men, taking antidepressant medication, and social
and emotional loneliness. CLINICAL RELEVANCE: A good patient-provider
relationship can help to promote decreased acute or chronic stressors, increased
family and social support, decreased loneliness, modification of unhealthy
lifestyles such as smoking, obesity, physical inactivity, alcohol, control of
CRP, and antidepressant medication. Nurses are well placed to help prevent
physical diseases through detection and referral of patients who are depressed or
undiagnosed and not receiving adequate mental health treatment.
PMID- 28692783
TI - Rituximab for Antineutrophil Cytoplasmic Antibody-Associated Vasculitis-Not
Everything in the Garden Is Rosy: Comment on the Article by Cortazar et al.
PMID- 28692782
TI - A comparison of bivariate, multivariate random-effects, and Poisson correlated
gamma-frailty models to meta-analyze individual patient data of ordinal scale
diagnostic tests.
AB - Individual patient data (IPD) meta-analyses are increasingly common in the
literature. In the context of estimating the diagnostic accuracy of ordinal or
semi-continuous scale tests, sensitivity and specificity are often reported for a
given threshold or a small set of thresholds, and a meta-analysis is conducted
via a bivariate approach to account for their correlation. When IPD are
available, sensitivity and specificity can be pooled for every possible
threshold. Our objective was to compare the bivariate approach, which can be
applied separately at every threshold, to two multivariate methods: the ordinal
multivariate random-effects model and the Poisson correlated gamma-frailty model.
Our comparison was empirical, using IPD from 13 studies that evaluated the
diagnostic accuracy of the 9-item Patient Health Questionnaire depression
screening tool, and included simulations. The empirical comparison showed that
the implementation of the two multivariate methods is more laborious in terms of
computational time and sensitivity to user-supplied values compared to the
bivariate approach. Simulations showed that ignoring the within-study correlation
of sensitivity and specificity across thresholds did not worsen inferences with
the bivariate approach compared to the Poisson model. The ordinal approach was
not suitable for simulations because the model was highly sensitive to user
supplied starting values. We tentatively recommend the bivariate approach rather
than more complex multivariate methods for IPD diagnostic accuracy meta-analyses
of ordinal scale tests, although the limited type of diagnostic data considered
in the simulation study restricts the generalization of our findings.
PMID- 28692784
TI - Layer-Tunable Phosphorene Modulated by the Cation Insertion Rate as a Sodium
Storage Anode.
AB - Liquid phase exfoliation of few-layer phosphorene (FL-P) is extensively explored
in recent years. Nevertheless, their deficiencies such as ultralong sonication
time, limited flake size distribution, and uncontrollable thicknesses are major
hurdles for the development of phosphorene-based materials. Herein,
electrochemical cationic intercalation has been introduced to prepare
phosphorene, through which large-area FL-P without surface functional groups can
be efficiently attained (less than 1 h). More importantly, its layer number (from
2 to 11 layers) can be manipulated by changing the applied potential. The as
obtained phosphorene delivers superior sodium-storage performances when directly
utilized as an anode material in sodium-ion batteries. This electrochemical
cation insertion method to prepare phosphorene should greatly facilitate the
development of phosphorene-based technologies. Moreover, this work provides the
possibility for the scalable preparation of monolayer 2D materials by exploring
intercalation ions. Additionally, the successful electrochemical exfoliation of
phosphorene can promote the application of electrochemical exfoliation in other
2D materials.
PMID- 28692785
TI - Can a Time Fractional-Derivative Model Capture Scale-Dependent Dispersion in
Saturated Soils?
AB - Time nonlocal transport models such as the time fractional advection-dispersion
equation (t-fADE) were proposed to capture well-documented non-Fickian dynamics
for conservative solutes transport in heterogeneous media, with the underlying
assumption that the time nonlocality (which means that the current concentration
change is affected by previous concentration load) embedded in the physical
models can release the effective dispersion coefficient from scale dependency.
This assumption, however, has never been systematically examined using real data.
This study fills this historical knowledge gap by capturing non-Fickian transport
(likely due to solute retention) documented in the literature (Huang et al. 1995)
and observed in our laboratory from small to intermediate spatial scale using the
promising, tempered t-fADE model. Fitting exercises show that the effective
dispersion coefficient in the t-fADE, although differing subtly from the
dispersion coefficient in the standard advection-dispersion equation, increases
nonlinearly with the travel distance (varying from 0.5 to 12 m) for both
heterogeneous and macroscopically homogeneous sand columns. Further analysis
reveals that, while solute retention in relatively immobile zones can be
efficiently captured by the time nonlocal parameters in the t-fADE, the motion
independent solute movement in the mobile zone is affected by the spatial
evolution of local velocities in the host medium, resulting in a scale-dependent
dispersion coefficient. The same result may be found for the other standard time
nonlocal transport models that separate solute retention and jumps (i.e.,
displacement). Therefore, the t-fADE with a constant dispersion coefficient
cannot capture scale-dependent dispersion in saturated porous media, challenging
the application for stochastic hydrogeology methods in quantifying real-world,
preasymptotic transport. Hence improvements on time nonlocal models using, for
example, the novel subordination approach are necessary to incorporate the
spatial evolution of local velocities without adding cumbersome parameters.
PMID- 28692786
TI - Chemically Addressable Perovskite Nanocrystals for Light-Emitting Applications.
AB - Whereas organic-inorganic hybrid perovskite nanocrystals (PNCs) have remarkable
potential in the development of optoelectronic materials, their relatively poor
chemical and colloidal stability undermines their performance in optoelectronic
devices. Herein, this issue is addressed by passivating PNCs with a class of
chemically addressable ligands. The robust ligands effectively protect the PNC
surfaces, enhance PNC solution processability, and can be chemically addressed by
thermally induced crosslinking or radical-induced polymerization. This thin
polymer shield further enhances the photoluminescence quantum yields by removing
surface trap states. Crosslinked methylammonium lead bromide (MAPbBr3 ) PNCs are
applied as active materials to build light-emitting diodes that have low turn-on
voltages and achieve a record luminance of over 7000 cd m-2 , around threefold
better than previous reported MA-based PNC devices. These results indicate the
great potential of this ligand passivation approach for long lifespan, highly
efficient PNC light emitters.
PMID- 28692787
TI - Thermodynamically Stable Synthesis of Large-Scale and Highly Crystalline
Transition Metal Dichalcogenide Monolayers and their Unipolar n-n Heterojunction
Devices.
AB - Transition metal dichalcogenide (TMDC) monolayers are considered to be potential
materials for atomically thin electronics due to their unique electronic and
optical properties. However, large-area and uniform growth of TMDC monolayers
with large grain sizes is still a considerable challenge. This report presents a
simple but effective approach for large-scale and highly crystalline molybdenum
disulfide monolayers using a solution-processed precursor deposition. The low
supersaturation level, triggered by the evaporation of an extremely thin
precursor layer, reduces the nucleation density dramatically under a
thermodynamically stable environment, yielding uniform and clean monolayer films
and large crystal sizes up to 500 um. As a result, the photoluminescence exhibits
only a small full-width-half-maximum of 48 meV, comparable to that of exfoliated
and suspended monolayer crystals. It is confirmed that this growth procedure can
be extended to the synthesis of other TMDC monolayers, and robust MoS2 /WS2
heterojunction devices are easily prepared using this synthetic procedure due to
the large-sized crystals. The heterojunction device shows a fast response time
(~45 ms) and a significantly high photoresponsivity (~40 AW-1 ) because of the
built-in potential and the majority-carrier transport at the n-n junction. These
findings indicate an efficient pathway for the fabrication of high-performance 2D
optoelectronic devices.
PMID- 28692788
TI - Watershed vs. within-lake drivers of nitrogen: phosphorus dynamics in shallow
lakes.
AB - Research on lake eutrophication often identifies variables affecting amounts of
phosphorus (P) and nitrogen (N) in lakes, but understanding factors influencing
N:P ratios is important given its influence on species composition and toxin
production by cyanobacteria. We sampled 80 shallow lakes in Minnesota (USA) for
three years to assess effects of watershed size, proportion of watershed as both
row crop and natural area, fish biomass, and lake alternative state (turbid vs.
clear) on total N : total P (TN : TP), ammonium, total dissolved phosphorus
(TDP), and seston stoichiometry. We also examined N:P stoichiometry in 20
additional lakes that shifted states during the study. Last, we assessed the
importance of denitrification by measuring denitrification rates in sediment
cores from a subset of 34 lakes, and by measuring seston delta15 N in four
additional experimental lakes before and after they were experimentally
manipulated from turbid to clear states. Results showed alternative state had the
largest influence on overall N:P stoichiometry in these systems, as it had the
strongest relationship with TN : TP, seston C:N:P, ammonium, and TDP. Turbid
lakes had higher N at given levels of P than clear lakes, with TN and ammonium 2
fold and 1.4-fold higher in turbid lakes, respectively. In lakes that shifted
states, TN was 3-fold higher in turbid lakes, while TP was only 2-fold higher,
supporting the notion N is more responsive to state shifts than is P. Seston
delta15 N increased after lakes shifted to clear states, suggesting higher
denitrification rates may be important for reducing N levels in clear states, and
potential denitrification rates in sediment cores were among the highest recorded
in the literature. Overall, our results indicate lake state was a primary driver
of N:P dynamics in shallow lakes, and lakes in clear states had much lower N at a
given level of P relative to turbid lakes, likely due to higher denitrification
rates. Shallow lakes are often managed for the clear-water state due to increased
value as wildlife habitat. However, our results indicate lake state also
influences N biogeochemistry, such that managing shallow lakes for the clear
water state may also mitigate excess N levels at a landscape scale.
PMID- 28692789
TI - Optimization and standardization of fluorescent cell barcoding for multiplexed
flow cytometric phenotyping.
AB - Fluorescent cell barcoding (FCB) is a cell-based multiplexing technique for high
throughput flow cytometry. Barcoded samples can be stained and acquired
collectively, minimizing staining variability and antibody consumption, and
decreasing required sample volumes. Combined with functional measurements, FCB
can be used for drug screening, signaling profiling, and cytokine detection, but
technical issues are present. We optimized the FCB technique for routine
utilization using DyLight 350, DyLight 800, Pacific Orange, and CBD500 for
barcoding six, nine, or 36 human peripheral blood specimens. Working
concentrations of FCB dyes ranging from 0 to 500 MUg/ml were tested, and
viability dye staining was optimized to increase robustness of data. A five-color
staining with surface markers for Vbeta usage analysis in CD4+ and CD8+ T cells
was achieved in combination with nine sample barcoding. We provide improvements
of the FCB technique that should be useful for multiplex drug screening and for
lymphocyte characterization and perturbations in the diagnosis and during the
course of disease. Published 2017 by Wiley Periodicals, Inc., on behalf of
International Society for Advancement of Cytometry. This article is a US
government work and as such, is in the public domain in the United States of
America.
PMID- 28692790
TI - Formation of Mo-Polydopamine Hollow Spheres and Their Conversions to MoO2 /C and
Mo2 C/C for Efficient Electrochemical Energy Storage and Catalyst.
AB - Highly uniform hierarchical Mo-polydopamine hollow spheres are synthesized for
the first time through a liquid-phase reaction under ambient temperature. A self
assembly mechanism of the hollow structure of Mo-polydopamine precursor is
discussed in detail, and a determined theory is proposed in a water-in-oil
system. Via different annealing process, these precursors can be converted into
hierarchical hollow MoO2 /C and Mo2 C/C composites without any distortion in
shape. Owing to the well-organized structure and nanosize particle embedding, the
as-prepared hollow spheres exhibit appealing performance both as the anode
material for lithium-ion batteries and as the catalyst for hydrogen evolution
reaction (HER). Accordingly, MoO2 /C delivers a high reversible capacity of 940
mAh g-1 at 0.1 A g-1 and 775 mAh g-1 at 1 A g-1 with good rate capability and
long cycle performance. Moreover, Mo2 C/C also exhibits an enhanced
electrocatalytic performance with a low overpotential for HER in both acidic and
alkaline conditions, as well as remarkable stability.
PMID- 28692791
TI - Multistimuli Response Micro- and Nanolayers of a Coordination Polymer Based on
Cu2 I2 Chains Linked by 2-Aminopyrazine.
AB - A nonporous laminar coordination polymer of formula [Cu2 I2 (2-aminopyrazine)]n
is prepared by direct reaction between CuI and 2-aminopyrazine, two industrially
available building blocks. The fine tuning of the reaction conditions allows
obtaining [Cu2 I2 (2-aminopyrazine)]n in micrometric and nanometric sizes with
same structure and composition. Interestingly, both materials show similar
reversible thermo- and pressure-luminescent response as well as reversible
electrical response to volatile organic solvents such as acetic acid. X-ray
diffraction studies under different conditions, temperatures and pressures, in
combination with theoretical calculations allow rationalizing the physical
properties of this compound and its changes under physical stimuli. Thus, the
emission dramatically increases when lowering the temperature, while an
enhancement of the pressure produces a decrease in the emission intensity. These
observations emerge as a direct consequence of the high structural flexibility of
the Cu2 I2 chains which undergo a contraction in Cu?Cu distances as far as
temperature decreases or pressure increases. However, the strong structural
changes observed under high pressure lead to an unexpected effect that produces a
less effective Cu?Cu orbital overlapping that justifies the decrease in the
intensity emission. This work shows the high potential of materials based on Cu2
I2 chains for new applications.
PMID- 28692792
TI - Clinical and Molecular Phenotypes of Low-Penetrance Variants of NLRP3: Diagnostic
and Therapeutic Challenges.
AB - OBJECTIVE: Cryopyrin-associated periodic syndromes (CAPS) result from gain-of
function mutations in the NLRP3 gene, which causes excessive release of
interleukin-1beta (IL-1beta) and systemic inflammation. While pathogenetic NLRP3
variant phenotypes are well-characterized, low-penetrance NLRP3 variants
represent a significant clinical challenge. The aims of this study were to
determine the clinical phenotype, the in vitro biologic phenotype, and the effect
of anti-IL-1 treatment in patients with low-penetrance NLRP3 variants. METHODS: A
multicenter study of consecutive symptomatic patients with low-penetrance NLRP3
variants recruited from 7 centers between May 2012 and May 2013 was performed.
The observed findings were transferred into a study database, from which they
were extracted for analysis. Controls were patients with a known pathogenetic
NLRP3 variant. Clinical presentation and CAPS markers of inflammation were
captured. Functional assays of inflammasome activation, including caspase 1
activity, NF-kappaB release, cell death, and IL-1beta release, were performed.
Treatment effects of IL-1 were determined. Comparisons between low-penetrance and
pathogenetic NLRP3 variants were performed. RESULTS: The study included 45
patients, 21 of which were female (47%); 26 of the patients (58%) were children.
NLRP3 low-penetrance variants identified in the patients were Q703K (n = 19),
R488K (n = 6), and V198M (n = 20). In the controls, 28 had pathogenetic NLRP3
variants. Patients with low-penetrance NLRP3 variants had significantly more
fever (76%) and gastrointestinal symptoms (73%); eye disease, hearing loss, and
renal involvement were less common. Functional inflammasome testing identified an
intermediate phenotype in low-penetrance NLRP3 variants as compared to wild-type
and pathogenetic NLRP3 variants. All treated patients responded to IL-1
inhibition, with complete response documented in 50% of patients. CONCLUSION:
Patients with low-penetrance NLRP3 variants display a distinct clinical phenotype
and an intermediate biologic phenotype, including IL-1beta and non-IL-1beta
mediated inflammatory pathway activation.
PMID- 28692794
TI - Course of Grip Force Impairment in Patients With Early Rheumatoid Arthritis Over
the First Five Years After Diagnosis.
AB - OBJECTIVE: Objective measures of function are important in rheumatoid arthritis
(RA). The objective of this study was to investigate grip strength in patients
with early RA. METHODS: An inception cohort of 225 patients with early RA was
followed in accordance with a structured protocol. Average and peak grip force
values of the dominant hand (measured using a Grippit device [AB Detektor]) were
evaluated and compared to expected age- and sex-specific reference values from
the literature. Separate analyses were performed for those with limited self
reported disability (Health Assessment Questionnaire disability index [HAQ DI]
score <=0.5) and clinical remission (Disease Activity Score in 28 joints <2.6).
RESULTS: Baseline average grip force among RA patients was significantly lower
than the corresponding expected value (mean 105N versus 266N; P < 0.001).
Observed average and peak grip force values were significantly reduced compared
to those expected in women as well as in men over time and at all time points.
The average grip force improved significantly from inclusion to the 12-month
visit (age-corrected mean change 34N [95% confidence interval 26-43]). At 5
years, the average grip force was still lower than that expected overall (mean
139N versus 244N; P < 0.001), and also among those with HAQ DI scores <=0.5 and
those in clinical remission. CONCLUSION: Grip strength improved in early RA
patients, particularly during the first year. However, it was still significantly
impaired 5 years after diagnosis, even among those with limited self-reported
disability and those in clinical remission. This suggests that further efforts to
improve hand function are important in early RA.
PMID- 28692793
TI - Rare X Chromosome Abnormalities in Systemic Lupus Erythematosus and Sjogren's
Syndrome.
AB - OBJECTIVE: Sjogren's syndrome (SS) and systemic lupus erythematosus (SLE) are
related by clinical and serologic manifestations as well as genetic risks. Both
diseases are more commonly found in women than in men, at a ratio of ~10 to 1.
Common X chromosome aneuploidies, 47,XXY and 47,XXX, are enriched among men and
women, respectively, in either disease, suggesting a dose effect on the X
chromosome. METHODS: We examined cohorts of SS and SLE patients by constructing
intensity plots of X chromosome single-nucleotide polymorphism alleles, along
with determining the karyotype of selected patients. RESULTS: Among ~2,500 women
with SLE, we found 3 patients with a triple mosaic, consisting of
45,X/46,XX/47,XXX. Among ~2,100 women with SS, 1 patient had 45,X/46,XX/47,XXX,
with a triplication of the distal p arm of the X chromosome in the 47,XXX cells.
Neither the triple mosaic nor the partial triplication was found among the
controls. In another SS cohort, we found a mother/daughter pair with partial
triplication of this same region of the X chromosome. The triple mosaic occurs in
~1 in 25,000-50,000 live female births, while partial triplications are even
rarer. CONCLUSION: Very rare X chromosome abnormalities are present among
patients with either SS or SLE and may inform the location of a gene(s) that
mediates an X dose effect, as well as critical cell types in which such an effect
is operative.
PMID- 28692795
TI - Macroporous Inverse Opal-like MoxC with Incorporated Mo Vacancies for
Significantly Enhanced Hydrogen Evolution.
AB - The hydrogen evolution reaction (HER) is one of the most important pathways for
producing pure and clean hydrogen. Although platinum (Pt) is the most efficient
HER electrocatalyst, its practical application is significantly hindered by high
cost and scarcity. In this work, an MoxC with incorporated Mo vacancies and
macroporous inverse opal-like (IOL) structure (MoxC-IOL) was synthesized and
studied as a low-cost efficient HER electrocatalyst. The macroporous IOL
structure was controllably fabricated using a facile-hard template strategy. As a
result of the combined benefits of the Mo vacancies and structural advantages,
including appropriate hydrogen binding energy, large exposed surface, robust IOL
structure and fast mass/charge transport, the synthesized MoxC-IOL exhibited
significantly enhanced HER electrocatalytic performance with good stability, with
performance comparable or superior to Pt wire in both acidic and alkaline
solutions.
PMID- 28692796
TI - Atorvastatin as a Promising Crystallization Inhibitor of Amorphous Probucol:
Dielectric Studies at Ambient and Elevated Pressure.
AB - The aim of this article was to check the physical stability of the amorphous form
of probucol at both standard storage and manufacturing conditions. Our studies
clearly show that disordered form of the examined, cholesterol lowering, agent
stored at ambient pressure does not reveal any tendency toward recrystallization.
The physical stability of neat probucol stored at ambient pressure has been
investigated (i) at room temperature by means of X-ray diffraction technique
(XRD) as well as (ii) at T = 333 K by means of broadband dielectric spectroscopy
(BDS). Due to the fact that compression is an important stage of drugs
manufacturing we additionally performed physical stability tests of amorphous
probucol at elevated pressure. The recrystallization tendency of the examined
pharmaceutical has been tracked online from the initial and further up to a few
hours after compression by means of the high pressure BDS technique. These
experiments indicate that even very small pressure applied during the sample
compression immediately induce its recrystallization. Since, the sensitivity on
pressure eliminates probucol from the group of physically stable amorphous APIs,
its stabilization is required. Taking into account that there are many scientific
reports describing the positive effect of coadministration of probucol with the
drug atorvastatin, we used the latter as probucol's crystallization inhibitor.
PMID- 28692797
TI - Versatile Large-Area Custom-Feature van der Waals Epitaxy of Topological
Insulators.
AB - As the focus of applied research in topological insulators (TI) evolves, the need
to synthesize large-area TI films for practical device applications takes center
stage. However, constructing scalable and adaptable processes for high-quality TI
compounds remains a challenge. To this end, a versatile van der Waals epitaxy
(vdWE) process for custom-feature bismuth telluro-sulfide TI growth and
fabrication is presented, achieved through selective-area fluorination and
modification of surface free-energy on mica. The TI features grow epitaxially in
large single-crystal trigonal domains, exhibiting armchair or zigzag crystalline
edges highly oriented with the underlying mica lattice and only two preferred
domain orientations mirrored at 180 degrees . As-grown feature thickness
dependence on lateral dimensions and denuded zones at boundaries are observed, as
explained by a semiempirical two-species surface migration model with robust
estimates of growth parameters and elucidating the role of selective-area surface
modification. Topological surface states contribute up to 60% of device
conductance at room temperature, indicating excellent electronic quality. High
yield microfabrication and the adaptable vdWE growth mechanism with readily
alterable precursor and substrate combinations lend the process versatility to
realize crystalline TI synthesis in arbitrary shapes and arrays suitable for
facile integration with processes ranging from rapid prototyping to scalable
manufacturing.
PMID- 28692799
TI - Highly Stable Organic Small Molecular Nanoparticles as an Advanced and
Biocompatible Phototheranostic Agent of Tumor in Living Mice.
AB - Near-infrared (NIR)-absorbing organic small molecules hold great promise as the
phototheranostic agents for clinical translation by virtue of their intrinsic
advantages such as well-defined chemical structure, high purity, and good
reproducibility. However, most of the currently available ones face the
challenges in varying degrees in terms of photothermal instability, and
photobleaching/reactive oxygen nitrogen species (RONS) inresistance, which indeed
impair their practical applications in precise diagnosis and treatment of
diseases. Herein, we developed highly stable and biocompatible organic
nanoparticles (ONPs) for effective phototheranostic application by design and
synthesis of an organic small molecule (namely TPA-T-TQ) with intensive
absorption in the NIR window. The TPA-T-TQ ONPs with no noticeable in vivo
toxicity possess better capacities in photothermal conversion and photoacoustic
imaging (PAI), as well as show far higher stabilities including
thermal/photothermal stabilities, and photobleaching/RONS resistances, when
compared with the clinically popularly used indocyanine green. Thanks to the
combined merits, the ONPs can serve as an efficient probe for in vivo PAI in a
high-contrast manner, which also significantly causes the stoppage of tumor
growth in living mice through PAI-guided photothermal therapy. This study thus
provides an insight into the development of advanced NIR-absorbing small
molecules for practical phototheranostic applications.
PMID- 28692798
TI - Backbone Hydrogen Bond Strengths Can Vary Widely in Transmembrane Helices.
AB - Although backbone hydrogen bonds in transmembrane (TM) helices have the potential
to be very strong due to the low dielectric and low water environment of the
membrane, their strength has never been assessed experimentally. Moreover,
variations in hydrogen bond strength might be necessary to facilitate the TM
helix breaking and bending that is often needed to satisfy functional
imperatives. Here we employed equilibrium hydrogen/deuterium fractionation
factors to measure backbone hydrogen bond strengths in the TM helix of the
amyloid precursor protein (APP). We find an enormous range of hydrogen bond free
energies, with some weaker than water-water hydrogen bonds and some over 6
kcal/mol stronger than water-water hydrogen bonds. We find that weak hydrogen
bonds are at or near preferred gamma-secretase cleavage sites, suggesting that
the sequence of APP and possibly other cleaved TM helices may be designed, in
part, to make their backbones accessible for cleavage. The finding that hydrogen
bond strengths in a TM helix can vary widely has implications for membrane
protein function, dynamics, evolution, and design.
PMID- 28692800
TI - N6-Formyllysine as a Biomarker of Formaldehyde Exposure: Formation and Loss of N6
Formyllysine in Nasal Epithelium in Long-Term, Low-Dose Inhalation Studies in
Rats.
AB - Exposure to both endogenous and exogenous formaldehyde has been established to be
carcinogenic, likely by virtue of forming nucleic acid and proteins adducts such
as N6-formyllysine. To better assess N6-formyllysine as a biomarker of
formaldehyde exposure, we studied accumulation of N6-formyllysine adducts in
tissues of rats exposed by inhalation to 2 ppm [13C2H2]-formaldehyde for 7, 14,
21, and 28 days (6 h/day) and investigated adduct loss over a 7-day postexposure
period using liquid chromatography-coupled tandem mass spectrometry. Our results
showed formation of exogenous adducts in nasal epithelium and to some extent in
trachea but not in distant tissues of lung, bone marrow, or white blood cells,
with a 2-fold increase over endogenous N6-formyllysine over a 3-week exposure
period. Postexposure analyses indicated a biexponential decay of N6-formyllysine
in proteins extracted from different cellular compartments, with half-lives of
~25 and ~182 h for the fast and slow phases, respectively, in cytoplasmic
proteins. These results parallel the behavior of DNA adducts and DNA-protein
cross-links, with protein adducts cleared faster than DNA-protein cross-links,
and point to the potential utility of N6-formyllysine protein adducts as
biomarkers of formaldehyde.
PMID- 28692801
TI - UV-Curable Antismudge Coatings.
AB - Current antismudge coatings that bear nano-pools of a grafted liquid ingredient
for dewetting enablement (NP-GLIDE) are cured at high temperatures, which are
undesirable for application on heat-sensitive substrates. Reported herein is the
development of a NP-GLIDE coating that can be photocured at room temperature. Of
the various formulations that have been tested, robust coatings were obtained
from one recipe consisting of a photoinitiator, a trifunctional monomer that
bears three double bonds, and a graft copolymer. The last bears pendent double
bonds and a poly(dimethylsiloxane) (PDMS) side chain as the antismudge agent.
Coatings were prepared by casting films from a solution containing these three
components and then photolyzing the resultant films. A systematic study revealed
that the liquid sliding property developed on the coating at a lower cross
linking density than that required for ink to contract. Further, retaining the
ability to contract ink traces after many writing and erasing cycles was the most
demanding of the three antismudge tests. For our optimized formulation, only 5
min of irradiation was required to yield a transparent coating with superior
antismudge properties. Moreover, irradiating selected regions and then removing,
with a solvent, reagents in the nonirradiated regions can yield a surface with
patterned wettability. These advantageous properties of the new photocurable
coating facilitate its applications.
PMID- 28692802
TI - Reversible Protonated Resting State of the Nitrogenase Active Site.
AB - Protonated states of the nitrogenase active site are mechanistically significant
since substrate reduction is invariably accompanied by proton uptake. We report
the low pH characterization by X-ray crystallography and EPR spectroscopy of the
nitrogenase molybdenum iron (MoFe) proteins from two phylogenetically distinct
nitrogenases (Azotobacter vinelandii, Av, and Clostridium pasteurianum, Cp) at
pHs between 4.5 and 8. X-ray data at pHs of 4.5-6 reveal the repositioning of
side chains along one side of the FeMo-cofactor, and the corresponding EPR data
shows a new S = 3/2 spin system with spectral features similar to a state
previously observed during catalytic turnover. The structural changes suggest
that FeMo-cofactor belt sulfurs S3A or S5A are potential protonation sites.
Notably, the observed structural and electronic low pH changes are correlated and
reversible. The detailed structural rearrangements differ between the two MoFe
proteins, which may reflect differences in potential protonation sites at the
active site among nitrogenase species. These observations emphasize the benefits
of investigating multiple nitrogenase species. Our experimental data suggest that
reversible protonation of the resting state is likely occurring, and we term this
state "E0H+", following the Lowe-Thorneley naming scheme.
PMID- 28692803
TI - Flat Graphene-Enhanced Electron Transfer Involved in Redox Reactions.
AB - Graphene is easily warped in the out-of-plane direction because of its high in
plane Young's modulus, and exploring the influence of wrinkled graphene on its
properties is essential for the design of graphene-based materials for
environmental applications. Herein, we prepared wrinkled graphene (WGN-1 and WGN
2) by thermal treatment and compared their electrochemical properties with those
of flat graphene nanosheets (FGN). FGN exhibit activities that are much better
than those of wrinkled graphene nanosheets (WGN), not only in the electrochemical
oxidation of methylene blue (MB) but also in the electrochemical reduction of
nitrobenzene (NB). Transformation ratios of MB and NB in FGN, WGN-1, and WGN-2
were 97.5, 80.1, and 57.9% and 94.6, 92.1, and 81.2%, respectively.
Electrochemical impedance spectroscopy and the surface resistance of the graphene
samples increased in the following order: FGN < WGN-1 < WGN-2. This suggests that
the reaction charges transfer faster across the reaction interfaces and along the
surface of FGN than that of WGN, and wrinkles restrict reaction charge transfer
and reduce the reaction rates. This study reveals that the morphology of the
graphene (flat or wrinkle) greatly affects redox reaction activities and may have
important implications for the design of novel graphene-based nanostructures and
for our understanding of graphene wrinkle-dependent redox reactions in
environmental processes.
PMID- 28692804
TI - Dynamic Nuclear Polarization Efficiency Increased by Very Fast Magic Angle
Spinning.
AB - Dynamic nuclear polarization (DNP) has recently emerged as a tool to enhance the
sensitivity of solid-state NMR experiments. However, so far high enhancements
(>100) are limited to relatively low magnetic fields, and DNP at fields higher
than 9.4 T significantly drops in efficiency. Here we report solid-state
Overhauser effect DNP enhancements of over 100 at 18.8 T. This is achieved
through the unexpected discovery that enhancements increase rapidly with
increasing magic angle spinning (MAS) rates. The measurements are made using 1,3
bisdiphenylene-2-phenylallyl dissolved in o-terphenyl at 40 kHz MAS. We introduce
a source-sink diffusion model for polarization transfer which is capable of
explaining the experimental observations. The advantage of this approach is
demonstrated on mesoporous alumina with the acquisition of well-resolved DNP
surface-enhanced 27Al cross-polarization spectra.
PMID- 28692805
TI - Stability, Scale-up, and Performance of Quantum Dot Solar Cells with Carbonate
Treated Titanium Oxide Films.
AB - A novel yet simple approach of carbonate (CBN) treatment of TiO2 films is
performed, and quantum dot solar cells (QDSCs) with high power conversion
efficiencies (PCEs), reasonably good stabilities, and good fill factors (FFs) are
fabricated with TiO2-CBN films. The ability of carbonate groups to passivate
defects or oxygen vacancies of TiO2 is confirmed from a nominally enhanced band
gap, a lowered defect induced fluorescence intensity, an additional Ti-OH signal
obtained after carbonate decomposition, and a more capacitive low frequency
electrochemical impedance behavior achieved for TiO2-CBN compared to untreated
TiO2. A large area QDSC of 1 cm2 with a TiO2-CBN/CdS/Au@PAA (poly(acrylic acid))
photoanode delivers an enhanced PCE of 4.32% as opposed to 3.03% achieved for its
analogous cell with untreated TiO2. Impedance analysis illustrates the role of
carbonate treatment in increasing the recombination resistance at the
photoanode/electrolyte interfaces and in suppressing back-electron transfer to
the electrolyte, thus validating the superior PCE achieved for the cell with
carbonate-treated TiO2. QDSCs with the configuration TiO2-CBN/CdS/Au@PAA
polysulfide/SiO2 gel-carbon-fabric/WO3-x and active areas of 0.2-0.3 cm2 yield
efficiencies in the range of 5.16 to 6.3%, and the average efficiency of the
cells is 5.9%. The champion cell is characterized by the following photovoltaic
parameters: JSC (short circuit current density), 11.04 mA cm-2; VOC (open circuit
voltage), 0.9 V; FF, 0.63; and PCE, 6.3%. Stability tests performed on this cell
show that dark storage has a less deleterious effect on cell performance compared
to extended illumination. In dark, the PCE of the cell dropped from 5.69 to
5.52%, and under prolonged continuous irradiance of 5 h, it decreased from 5.91
to 4.83%. A scaled-up QDSC with the same architecture of 4 cm2 size showed a PCE
of 1.06%, and the demonstration of the lighting of a LED accomplished using this
cell exemplifies that this cell can be used for powering electronic devices that
require low power.
PMID- 28692806
TI - MicroRNA-155-3p Mediates TNF-alpha-Inhibited Cementoblast Differentiation.
AB - Periodontitis is a prevalent and chronic inflammatory disease that is
interrelated with systemic health. Periodontitis can be promoted by tumor
necrosis factor alpha (TNF-alpha). Cementum, a vital part of the periodontium, is
a bone-like mineralized tissue that is produced by cementoblasts. Our laboratory
previously revealed that TNF-alpha inhibits cementoblast differentiation and
mineralization. However, how TNF-alpha modulates cementoblast differentiation and
mineralization remains largely unknown. MicroRNA-155 (miR-155) is induced and
regulates TNF-alpha-inhibited osteogenic differentiation. In this study, we found
that miR-155-3p was increased during TNF-alpha-stimulated OCCM-30 cells and
involved in cementoblast differentiation and mineralization. Overexpression of
miR-155-3p suppressed cementoblast mineralization. Bioinformatics analysis
revealed that potassium channel tetramerization domain containing 1 ( Kctd1) is a
candidate target gene of miR-155-3p. Moreover, miR-155-3p overexpression
suppressed KCTD1 levels. Meanwhile, its knockdown increased KCTD1 expression.
Transfection with miR-155-3p also inhibited the luciferase activity of 3'
untranslated regions in the Kctd1 wild type but not the mutant. These data
indicated that Kctd1 is a direct and novel target of miR-155-3p. The Wnt
signaling pathway inhibits cementoblast differentiation, and we further
demonstrated that miR-155-3p partially modulates cementoblast differentiation
through the canonical Wnt signaling pathway. In addition to the gain/loss
function assay of miR-155-3p, the luciferase activity assay of canonical Wnt
signaling was performed. The assays revealed that miR-155-3p increased beta
catenin-mediated transcriptional activation. Overall, our data clarified that miR
155-3p mediated TNF-alpha-inhibited cementoblast differentiation by targeting
Kctd1, at least partially through canonical Wnt signaling pathway. These findings
reveal the expanded function of miRNAs in cementoblast differentiation and
mineralization.
PMID- 28692807
TI - The effect of moderate consumption of non-nutritive sweeteners on glucose
tolerance and body composition in rats.
AB - Glucose tolerance and body composition were determined in male rats given non
nutritive sweeteners (NNS) (aspartame or sucralose) in drinking water. Areas
under the curve for glucose and insulin with NNS did not differ from control. NNS
treatment had no effect on weight gain or percent body fat. Epididymal fat pad
mass was higher with aspartame and the ratio of trunk to total fat was less with
sucralose versus control, suggesting that NNS consumption altered body fat
distribution.
PMID- 28692808
TI - Modulating Wnt Signaling Rescues Palate Morphogenesis in Pax9 Mutant Mice.
AB - Cleft palate is a common birth defect caused by disruption of palatogenesis
during embryonic development. Although mutations disrupting components of the Wnt
signaling pathway have been associated with cleft lip and palate in humans and
mice, the mechanisms involving canonical Wnt signaling and its regulation in
secondary palate development are not well understood. Here, we report that
canonical Wnt signaling plays an important role in Pax9-mediated regulation of
secondary palate development. We found that cleft palate pathogenesis in Pax9
deficient embryos is accompanied by significantly reduced expression of Axin2, an
endogenous target of canonical Wnt signaling, in the developing palatal
mesenchyme, particularly in the posterior regions of the palatal shelves. We
found that expression of Dkk2, encoding a secreted Wnt antagonist, is
significantly increased whereas the levels of active beta-catenin protein, the
essential transcriptional coactivator of canonical Wnt signaling, is
significantly decreased in the posterior regions of the palatal shelves in
embryonic day 13.5 Pax9-deficent embryos in comparison with control littermates.
We show that small molecule-mediated inhibition of Dickkopf (DKK) activity in
utero during palatal shelf morphogenesis partly rescued secondary palate
development in Pax9-deficient embryos. Moreover, we found that genetic
inactivation of Wise, which is expressed in the developing palatal shelves and
encodes another secreted antagonist of canonical Wnt signaling, also rescued
palate morphogenesis in Pax9-deficient mice. Furthermore, whereas Pax9del/del
embryos exhibit defects in palatal shelf elevation/reorientation and significant
reduction in accumulation of hyaluronic acid-a high molecular extracellular
matrix glycosaminoglycan implicated in playing an important role in palatal shelf
elevation-80% of Pax9del/del;Wise-/- double-mutant mouse embryos exhibit rescued
palatal shelf elevation/reorientation, accompanied by restored hyaluronic acid
accumulation in the palatal mesenchyme. Together, these data identify a crucial
role for canonical Wnt signaling in acting downstream of Pax9 to regulate palate
morphogenesis.
PMID- 28692815
TI - Efficient generation of goats with defined point mutation (I397V) in GDF9 through
CRISPR/Cas9.
AB - The recent emergence of the clustered regularly interspaced short palindromic
repeat (CRISPR)/CRISPR-associated (Cas) 9 system has attracted significant
attention for its potential to improve traits of agricultural importance.
However, most applications in livestock species to date have depended on aberrant
DNA repair to generate frameshifting indels. Whether this genomic engineering
technique involving homology-dependent repair (HDR) can be used to introduce
defined point mutations has been less explored. Previously, we reported a G->A
point mutation (g.231A>G, p.Val397Ile) in the growth differentiation factor 9
(GDF9) gene that has a large effect on the litter size of cashmere goats. In the
present study we report that by co-injecting synthesised RNAs and single-stranded
oligo deoxynucleotide (ssODN) donor sequences into goat zygotes, we successfully
introduced defined point mutations resulting in single amino acid substitutions
in the proteins as expected. The efficiency of this precise single-nucleotide
substitution in newborn kids was as high as 24% (4/17), indicating that ssODN
directed HDR via zygote injection is efficient at introducing point mutations in
the goat genome. The findings of the present study further highlight the complex
genome modifications facilitated by the CRISPR/Cas9 system, which is able to
introduce defined point mutations. This represents a significant development for
the improvement of reproduction traits in goats, as well as for validating the
roles of specific nucleotides in functional genetic elements in large animals.
PMID- 28692816
TI - Unique oestrogen receptor ligand-binding domain sequence of native parrots: a
possible link between phytoestrogens and breeding success.
AB - The New Zealand (NZ) native parrots kakapo, kaka and kea are classified as
critically endangered, endangered and vulnerable respectively. Successful
reproduction of kakapo and kaka is linked to years of high levels of fruiting in
native flora (mast years). To assess a possible hormonal link between native
plants and reproductive success in these parrots in mast years, we examined the
ligand-binding domains (LBD) of the progesterone receptor (PR), androgen receptor
(AR), estrogen receptor 1 (ESR1) and estrogen receptor 2 (ESR2) in NZ native
(kakapo, kaka, kea and kakariki) and non-native (Australian cockatiel) parrots
and compared them with those in the chicken. The amino acid sequences for PR, AR,
ESR1 and ESR2 shared >90% homology among the NZ parrots, the cockatiel and, in
most cases, the chicken. The exception was for the ESR1 LBD, which contained an
extra eight amino acids at the C-terminal in all the parrots compared with the
chicken and with published sequences of non-parrot species. These results support
the notion that the ESR1 LBD of parrots responds differently to putative
oestrogenic compounds in native trees in NZ during times of intermittent masting.
In turn, this may provide important information for generating parrot-specific
bioassays and linkages to steroidogenic activity in native plants.
PMID- 28692817
TI - Complications of hematopoietic stem cell transplantation: Bacterial infections.
AB - Bacterial infections remain a common complication of hematopoietic stem cell
transplantation (HSCT), especially in the pre-engraftment phase. The risk of
bacterial infections is mainly related to neutropenia, mucositis, and the
presence of vascular lines. Most parts of the world have witnessed a shift in
epidemiology toward Gram-negative bacteria; a large proportion of which are
resistant to fluoroquinolones, extended-spectrum beta-lactams, carbapenems, and
in some units even colistin. Meticulous infection control practices are essential
for prevention of bacterial infections in HSCT. The role of routine prophylactic
antibiotics is limited in settings with high rates of bacterial resistance. If
used, prophylactic antibiotics should be limited to high-risk patients, and the
agents are selected based on local resistance profiles. Neutropenic fever is a
medical emergency in most HSCT recipients. Prompt clinical evaluation is
paramount, along with the intravenous administration of appropriate empiric
antimicrobials, typically an antipseudomonal beta-lactam agent. Glycopeptides
should only be considered if the patient is hemodynamically unstable or Gram
positive infection is suspected. Additional Gram-negative agents, such as
colistin or aminoglycosides, may be added if extensive Gram-negative resistance
is expected. To mitigate increasing bacterial resistance, empiric antibiotic
regimens should be rationalized or discontinued as soon as possible.
PMID- 28692818
TI - Establishing an autologous versus allogeneic hematopoietic cell transplant
program in nations with emerging economies.
AB - More than 70,000 hematopoietic cell transplants are currently performed each
year, and these continue to increase every year. However, there is a significant
variation in the number of absolute transplants and transplant rates between
centers, countries, and global regions. The prospect for emerging countries to
develop a hematopoietic cell transplantation (HCT) program, as well as to decide
on whether autologous HCT (auto-HCT) or allogeneic HCT (allo-HCT) should be
established to start with, relies heavily on factors that can explain differences
between these two procedures. Major factors that will influence a decision about
establishing the type of HCT program are macroeconomic factors such as
organization of the healthcare network, available resources and infrastructure.
Prevalence of specific diseases in the region as well genetic background of
donors and recipients will also influence the mandate or priority of the HCT in
the national healthcare plan to explain some of the country-specific differences.
Furthermore, microeconomic factors play a role, such as center-specific
experience in treating various disorders requiring hematopoietic stem cell
transplantation, along with accreditation status and patient volume. The
objective of the transplant procedure was to improve the survival and quality of
life of patients. The regional difference that one notices in emerging countries
about the higher number of allo-HCT compared with auto-HCT procedures performed
is primarily based on suboptimal healthcare network in treating various malignant
disorders that are the primary indication for auto-stem cell transplantation. In
this context, nonmalignant disorders such as bone marrow failure syndromes,
inherited genetic disorders and hemoglobinopathies have become the major
indication for stem cell transplantation. Better understanding of these factors
will assist in establishing new transplant centers in the emerging countries to
achieve their specific objectives and positive outcome.
PMID- 28692819
TI - Physical activity modifies the influence of apolipoprotein E epsilon4 allele and
type 2 diabetes on dementia and cognitive impairment among older Mexican
Americans.
AB - INTRODUCTION: The etiologies of dementia are complex and influenced by genetic
and environmental factors including medical conditions. METHODS: We used Cox
regression model to estimate the individual and joint effects of physical
activity (PA), apolipoprotein E (APOE) epsilon4, and diabetes status on risk of
dementia and cognitive impairment without dementia (CIND) among 1438 cognitively
intact Mexican American elderly who were followed up to 10 years. RESULTS: The
risk of developing dementia/CIND was increased more than threefold in APOE
epsilon4 carriers or diabetics with low levels of PA compared with epsilon4
noncarriers or nondiabetics who engaged in high PA (epsilon4: hazard ratio [HR] =
3.44, 95% confidence interval [CI] = 1.85-6.39; diabetes: HR = 3.11, 95% CI =
1.87-5.18); the presence of all three risk factors increased risk by nearly 10
fold (HR = 9.49, 95% CI = 3.57-25.3). DISCUSSION: PA in elderly Hispanics
protects strongly against the onset of dementia/CIND, especially in APOE epsilon4
carriers and those who have diabetes.
PMID- 28692820
TI - Response letter.
PMID- 28692821
TI - Dental care utilization in patients with different types of dementia: A
longitudinal nationwide study of 58,037 individuals.
AB - INTRODUCTION: Dementia may be associated with discontinuation of regular dental
checkups, which in turn results in poorer oral health. METHODS: We investigated
the trend of change in dental care utilization and the number of teeth before and
after being diagnosed with dementia. Longitudinal cognitive- and dental health
related information were merged using data on 58,037 newly diagnosed individuals
from the Swedish Dementia Registry and Swedish Dental Health Register during 2007
to 2015. RESULTS: Following dementia diagnosis, rate of dental care visits
significantly declined. Individuals with mixed dementia, dementia with
parkinsonism, and those with more severe and faster cognitive impairment had
significantly higher rate of decline in dental care utilization. Vascular
dementia and lower baseline Mini-Mental State Examination score were significant
predictors of faster loss of teeth. DISCUSSION: Dental care utilization markedly
declines following dementia diagnosis. The reduction is more prominent in those
with rapid progressive cognitive impairment and the ones with extra frailty
burden.
PMID- 28692822
TI - A profile of Alan H. DeCherney, MD.
PMID- 28692823
TI - High HIV infection prevalence in a group of men who have sex with men.
AB - Brazil is characterized by a concentrated AIDS epidemic, it has a prevalence of
less than 1% in the general population. However, there are higher rates in
specific populations, especially in men who have sex with men. The study's aim
was to analyze the association between sociodemographic characteristics, sexual
practices, sexual behaviors and the HIV infection in a group of men who have sex
with men. Secondary data was collected between June 2014 and September 2015 in a
research of cross-sectional design in the city of Rio de Janeiro, Brazil.
Volunteers answered an online computerized questionnaire and took HIV test. Chi
squared distribution and multiple logistic regression was used. There were 341
participants. Most of them were racially mixed, single, average age of 30.6 years
and with a higher education level. The HIV prevalence was 13.9%. Two logistic
models were fit (insertive or receptive anal intercourse). Both models showed an
association with HIV among those who had a HIV positive sexual partner (Odds
Ratio~2.5) and a high self-perception of acquiring HIV (Model 1: Odds
Ratio~7/Model 2: Odds Ratio~10). Low condom usage in receptive anal intercourse
with casual partners had a direct association with HIV seropositivity, whereas
insertive anal intercourse with casual partners with or without condoms were
inversely related. The study identified a high prevalence of HIV infections among
a group of men who sex with men with a high self-perception risk of acquiring
HIV. The findings also showed a relation with sociodemographic and sexual
behavior variables.
PMID- 28692824
TI - Contextualizing educational differences in "vaccination uptake": A thirty nation
survey.
AB - This paper addresses the issue of public acceptance of vaccination with specific
attention being paid to the role of education in vaccine uptake. Using Flash
Eurobarometer 287 (2009) survey data and exploring it through the lens of Beck's
reflexive modernization and Roger's protection motivation theories we examined
how individual-level factors affect intention to get vaccinated, particularly
aimed at examining whether higher education predicts more or less vaccination
intention in different societies. The empirical results support an idea that at
least for seasonal flu educational differences in vaccination uptake are
contextual upon the reflexivity of the society in which respondent happens to
live. Educated people living in more reflexive modernized countries tend to
oppose vaccination against seasonal flu more that those highly educated living in
less advanced societies, indicating that skeptical attitude towards science that
is intrinsic to the modern post-industrial nations induces the immunization
opposition among most informed and distrustful social group.
PMID- 28692825
TI - Intergenerational social mobility and subjective wellbeing in later life.
AB - Whereas a great deal of literature has been devoted to investigating the link
between intergenerational social mobility and health, the few studies that have
examined the association between social mobility and life satisfaction have
produced conflicting findings. In the present study, we attempt to rectify
several shortcomings common to previous work by examining the association between
intergenerational social mobility and both life satisfaction and self-rated
health as measured in later-life. Our sample consisted of individuals born in
Scotland in 1936, who took part in the Scottish Mental Survey 1947 and were
subsequently followed-up into later-life. Regression analyses demonstrated that
satisfaction with life at age 78 was not significantly predicted by childhood or
adulthood socioeconomic status, or by the amount of social mobility experienced
from parental occupational social class. In contrast, self-rated health at age 78
was significantly predicted by adult socioeconomic status and by education, but
not by social mobility from parental occupational social class. These results
suggest that efforts to promote upwards social mobility may not result in better
subjective wellbeing, despite the apparent benefits for health.
PMID- 28692826
TI - Efficacy of non-vitamin-K antagonist oral anticoagulants for intracardiac thrombi
resolution in nonvalvular atrial fibrillation.
AB - Intracardiac thrombus is a potentially life-threatening condition associated with
atrial fibrillation (AF), with a high risk of embolic complications. Oral
anticoagulation (OAC) therapy is the first-line treatment for its prevention or
resolution. For many patients, traditional OAC treatment using vitamin K
antagonists (VKAs; e.g., warfarin) is limited by several factors and the advent
of non-VKA oral anticoagulants (NOACs), with improved efficacy and safety
profiles, has provided additional treatment options. However, studies are limited
in number and are mostly case reports or series, with only one published modest
size prospective multicenter cohort study for rivaroxaban. No randomized
controlled trials have been performed. Given the available data thus far, albeit
weak, NOACs offer a possible alternative to VKAs for treating intracardiac
thrombi.
PMID- 28692827
TI - Pathogenicity and genetic profile of oral Porphyromonas species from canine
periodontitis.
AB - OBJECTIVE: In this study, the presence of the prtC and fimA genes involved in the
pathogenicity of oral Porphyromonas spp. isolated from dogs with periodontitis
and healthy, as well as their genetic diversity was investigated. DESIGN: Thirty
two Beagle dogs, 24 with periodontitis and 8 healthy were evaluated. Subgingival
samples from only one gingival site of both groups were collected. Bacteria grown
in anaerobiosis were identified by RAPID ID 32A kits. From each strain the
respective DNA was obtained and used to genotyping by conventional PCR and AP
PCR. RESULTS: Dogs with periodontitis harbored 28 P. gulae, 2 P. creviocaricanis,
1 P. cangingivalis and 7 P. macacae; and from healthy dogs, 11 P. gulae and 5 P.
circumdentaria. In P. gulae isolated from periodontal dogs the gene prtC was
observed in 19 (67.85%) and in 7 (63.63%) from healthy dogs. P. gulae strains
from periodontal dogs harbored either the gene fimA I or fimA II; while strains
from healthy dogs harbored the gene fimA I, fimA II, fimA III or fimA IV, as well
as 1 P. circumdentaria the gene fimA II. By AP-PCR strains were grouped in
different clusters suggesting heterogeneity of these microorganisms. CONCLUSIONS:
The results presented herein inform that Porphyromonas spp. isolated from dogs
with and without periodontitis harbored the prtC and fimA genes and it could be a
role in the establishment of the infectious process.
PMID- 28692828
TI - Sleep bruxism and related risk factors in adults: A systematic literature review.
AB - OBJECTIVE: The aim of this article was to systematically review the literature to
assess the relationship between risk factors and sleep bruxism (SB) in adults
(age >=18 years). DESIGN: A systematic search of the following databases was
carried out: PubMed, Embase, Scopus, Cochrane Oral Health Group's Trial Register
and Cochrane Register of Controlled Trials, Web of Science, LILACs and SciELO.
Nine out of the 4583 initially identified articles were selected. This review was
conducted according to the guidelines from the Cochrane Handbook for Systematic
Reviews of Interventions, with reporting in agreement to the Preferred Reporting
Items for Systematic Reviews and Meta-analyses guidelines. RESULTS: Among the
nine analyzed articles, associations between SB and gastro-esophageal reflux
disease (GERD) (OR=6.6, CI=1.4-30.9) was found in one randomized clinical trial
(RCT). Four cross-sectional studies suggested history of SB during childhood
(OR=8.1 CI=5.4-12-2), age (OR=3.1, CI=2.3-4.1) and chronic migraine (OR=3.8,
C.I=1.8-7.8) as determinant factors for the development of SB. In one case
control study, patients with genetic polymorphisms were more likely to present SB
(OR=4.3, CI=1.6-11.3). Smoking (OR=2.8, CI=2.2-3.5) and alcohol intake (OR=1.9,
CI=1.2-2.8) showed moderate association in two case-control studies. CONCLUSIONS:
History of SB during childhood, gastro-esophageal reflux disease and genetic
polymorphisms seem to be important risk factors associated to SB in adults. Dry
mouth on awakening seems to be a protective factor. Association does not infer
with causality. Even if the evidence emerged from the considered studies was
clinically relevant, further studies are requested to better understand the
biological mechanisms behind the described associations.
PMID- 28692829
TI - Effects of melatonin on the proliferation and differentiation of human dental
pulp cells.
AB - OBJECTIVE: Effects of melatonin on the proliferation and differentiation of human
dental pulp cells (hDPCs) remain unclear. The purpose of this study was to
investigate the effect of melatonin on the proliferation and differentiation of
the hDPCs. DESIGN: Primary hDPCs were obtained from the third molar of volunteer
aged from 18 to 25. CCK8 assay evaluated the effect of melatonin upon cell
proliferation at day 1, 2, 3, 4, 5. After 7days' osteogenic induction with
melatonin or vehicle, alkaline phosphatase (ALP) activity was measured with a
commercial kit. Then levels of dentin sialophosphoprotein (DSPP) were determined
by immunocytochemical staining and western blot analysis, followed by
quantitative real-time reverse transcription-Polymerase chain reaction (qRT-PCR)
to analyse mRNA levels of ALP and DSPP. Finally hDPCs exposed to osteogenic
medium containing melatonin or vehicle for 14days were stained with alizarin red
to detect mineralization nodules formation. RESULTS: Melatonin significantly
inhibited the proliferative ability of the hDPCs in a concentration- and time
dependent manner. The hDPCs cultured in osteogenic induction medium with
melatonin presented an increase of ALP activity, expression of DSPP, mRNA levels
of ALP and DSPP, and mineralization nodules formation. CONCLUSIONS: These
findings indicate that melatonin at physiological concentrations can inhibit
proliferation and promote the differentiation of hDPCs, which might give some new
insights into the mechanism of regulating DPCs to achieve dentine regeneration.
PMID- 28692830
TI - Usability and clinical efficacy of diabetes mobile applications for adults with
type 2 diabetes: A systematic review.
AB - OBJECTIVES: To assess the usability and clinical effectiveness of diabetes mobile
applications (diabetes apps) developed for adults with type 2 diabetes. METHOD: A
systematic review of the usability and effectiveness of diabetes apps was
conducted. Searches were performed using MEDLINE, EMBASE, COMPENDEX, and IEEE
XPLORE for articles published from January 1, 2011, to January 17, 2017. Search
terms included: diabetes, mobile apps, and mobile health (mHealth). RESULTS: The
search yielded 723 abstracts of which seven usability studies and ten clinical
effectiveness studies met the inclusion criteria from 20 publications. Usability,
as measured by satisfaction ratings from experts and patients, ranged from 38% to
80%. Usability problem ratings ranged from moderate to catastrophic. Top
usability problems are multi-steps task, limited functionality and interaction,
and difficult system navigation. Clinical effectiveness, measured by reductions
in HbA1c, ranged from 0.15% to 1.9%. CONCLUSION: Despite meager satisfaction
ratings and major usability problems, there is some limited evidence supporting
the effectiveness of diabetes apps to improve glycemic control for adults with
type 2 diabetes. Findings strongly suggest that efforts to improve user
satisfaction, incorporate established principles of health behavior change, and
match apps to user characteristics will increase the therapeutic impact of
diabetes apps.
PMID- 28692831
TI - Children's quantitative Bayesian inferences from natural frequencies and number
of chances.
AB - Zhu and Gigerenzer (2006) showed that an appreciable number of Chinese children
aged between 9 and 12years old made correct quantitative Bayesian inferences
requiring the integration of priors and likelihoods as long as they were
presented with numerical information phrased in terms of natural frequencies. In
this study, we sought to replicate this finding and extend the investigation of
children's Bayesian reasoning to a different numerical format (chances) and other
probability questions (distributive and relative). In Experiment 1, a sample of
Italian children was presented with the natural frequency version of five
Bayesian inference problems employed by Zhu and Gigerenzer (2006), but only a
tiny minority of them were able to produce correct responses. In Experiment 2, we
found that the children's accuracy, as well as the coherence between their
probability judgments, depended on the type of question but not on the format
(natural frequency vs. chance) in which information was presented. We conclude
that children's competence in drawing quantitative Bayesian inferences is lower
than suggested by Zhu and Gigerenzer (2006) and, similarly to what happens with
adults, it relies more on a problem representation that fosters an extensional
evaluation of possibilities than on a specific numerical format.
PMID- 28692832
TI - Prevalence of child abuse in school environment in Kerala, India: An ICAST-CI
based survey.
AB - Very few studies focus on childhood abuse in developing countries and only a
small fraction of such studies explicitly deal with abuse in a school
environment. The purpose of this study was to estimate the prevalence of sexual,
physical, and emotional abuse in a school environment in a developing country.
Abuse history was collected using the International Society for the Prevention of
Child Abuse and Neglect (ISPCAN) Child Abuse Screening Tool - Children's
Institutional Version (ICAST-CI). Demographic variables were also collected.
Student supportive measures were provided both during and after the survey. 6682
school attending adolescents in Thrissur, Kerala participated in this cross
sectional self report study. One year and lifetime prevalence of physical (75.5%,
78.5%), emotional (84.5%, 85.7%) and sexual (21.0%, 23.8%) abuse was high. Abuse
was considered to be present even if an individual item from these three
categories was reported. Most abuse was reported as occurring 'sometimes' rather
than 'many times'. More males than females reported being victims of abuse;
figures for one-year prevalence were: physical abuse (83.4% vs. 61.7%), emotional
abuse (89.5% vs. 75.7%), and sexual abuse (29.5% vs. 6.2%). Various factors
significantly increase the likelihood of abuse-male gender, low socioeconomic
status, regular use of alcohol and drugs by family member at home, and having
other difficulties at school. Children tended to report abuse less frequently if
they liked attending school and if they always felt safe at school. The results
highlight the urgent need to address the issue of abuse in the school environment
and minimize its impact.
PMID- 28692833
TI - Falls and subjective well-being. Results of the population-based German Ageing
Survey.
AB - PURPOSE: The aim of the current study was to determine the relationship between
falling in the past 12 months and subjective well-being in a broader sense.
METHODS: Cross-sectional data were gathered from a representative sample of
community-dwelling individuals in the second half of life (40 to 95 years;
n=7808) in Germany. While life satisfaction was quantified using the Satisfaction
with Life Scale (SWLS), positive and negative affect was measured using the
Positive and Negative Affect Schedule (PANAS). RESULTS: The prevalence of falling
in the preceding 12 months was 17.6%. After controlling for sociodemographic
factors, various lifestyle factors, self-rated health, and morbidity, multiple
linear regression analysis revealed that falling in the past 12 months was
associated with higher negative affect (beta=0.08, p<0.001), lower positive
affect (beta=-0.04, p<0.05) as well as lower life satisfaction (beta=-0.12,
p<0.001). CONCLUSION: The present study stresses the relationship between falls
and subjective well-being. Future longitudinal studies are needed to validate the
findings of the present cross-sectional study and to better understand the nature
of this relationship.
PMID- 28692834
TI - Using National Ambient Air Quality Standards for fine particulate matter to
assess regional wildland fire smoke and air quality management.
AB - Wildland fire is an important ecological process in the California Sierra Nevada.
Personal accounts from pre-20th century describe a much smokier environment than
present day. The policy of suppression beginning in the early 20th century and
climate change are contributing to increased megafires. We use a single
particulate monitoring site at the wildland urban interface to explore impacts
from prescribed, managed, and full suppression wildland fires from 2006 to 2015
producing a contextual assessment of smoke impacts over time at the landscape
level. Prescribed fire had little effect on local fine particulate matter (PM2.5)
air quality with readings typical of similar non-fire times; hourly and daily
good to moderate Air Quality Index (AQI) for PM2.5, maximum hourly concentrations
21-103 MUg m-3, and mean concentrations between 7.7 and 13.2 MUg m-3. Hourly and
daily AQI was typically good or moderate during managed fires with 3 h and one
day reaching unhealthy while the site remained below National Ambient Air Quality
Standards (NAAQS), with maximum hourly concentrations 27-244 MUg m-3, and mean
concentrations 6.7-11.7 MUg m-3. The large high intensity fire in this area
created the highest short term impacts (AQI unhealthy for 4 h and very unhealthy
for 1 h), 11 unhealthy for sensitive days, and produced the only annual value
(43.9 MUg m-3) over the NAAQS 98th percentile for PM2.5 (35 MUg m-3). Pinehurst
remained below the federal standards for PM2.5 when wildland fire in the local
area was managed to 7800 ha (8-22% of the historic burn area). Considering air
quality impacts from smoke using the NAAQS at a landscape level over time can
give land and air managers a metric for broader evaluation of smoke impacts
particularly when assessing ecologically beneficial fire. Allowing managers to
control the amount and timing of individual wildland fire emissions can help
lessen large smoke impacts to public health from a megafire.
PMID- 28692835
TI - Biogeochemical oxidation of calcium sulfite hemihydrate to gypsum in flue gas
desulfurization byproduct using sulfur-oxidizing bacteria.
AB - Flue gas desulfurization (FGD) is a well-established air treatment technology for
coal and oil combustion gases that commonly uses lime or pulverized limestone
aqueous slurries to precipitate sulfur dioxide (SO2) as crystalline calcium
salts. Under forced oxidation (excess oxygen) conditions, FGD byproduct contains
almost entirely (>92%) gypsum (CaSO4.2H2O), a useful and marketable commodity. In
contrast, FGD byproduct formed in oxygen deficient oxidation systems contains a
high percentage of hannebachite (CaSO3.0.5H2O) to yield a material with no
commercial value, poor dewatering characteristics, and that is typically disposed
in landfills. Hannebachite in FGD byproduct can be chemically converted to
gypsum; however, the conditions that support rapid formation of gypsum require
large quantities of acids or oxidizers. This work describes a novel, patent
pending application of microbial physiology where a natural consortium of sulfur
oxidizing bacteria (SOB) was used to convert hannebachite-enriched FGD byproduct
into a commercially valuable, gypsum-enriched product (US Patent Assignment
503373611). To optimize the conversion of hannebachite into gypsum, physiological
studies on the SOB were performed to define their growth characteristics. The SOB
were found to be aerobic, mesophilic, neutrophilic, and dependent on a ready
supply of ammonia. They were capable of converting hannebachite to gypsum at a
rate of approximately five percent per day when the culture was applied to a 20
percent FGD byproduct slurry and SOB growth medium. 16S rDNA sequencing revealed
that the SOB consortium contained a variety of different bacterial genera
including both SOB and sulfate-reducing bacteria. Halothiobacillus, Thiovirga and
Thiomonas were the dominant sulfur-oxidizing genera.
PMID- 28692836
TI - Multi-body dynamic coupling mechanism for generating throwing arm velocity during
baseball pitching.
AB - The purpose of this study was to identify the detailed mechanism how the maximum
throwing arm endpoint velocity is determined by the muscular torques and non
muscular interactive torques from the perspective of the dynamic coupling among
the trunk, thorax and throwing and non-throwing arm segments. The pitching
movements of ten male collegiate baseball pitchers were measured by a three
dimensional motion capture system. Using the induced-segmental velocity analysis
(IVA) developed in this study, the maximum fingertip velocity of the throwing arm
(MFV) was decomposed into each contribution of the muscular torques, passive
motion-dependent torques due to gyroscopic moment, Coriolis force and centrifugal
force, and other interactive torque components. The results showed that MFV
(31.6+/-1.7m/s) was mainly attributed to two different mechanisms. The first is
the passive motion-dependent effect on increasing the angular velocities of three
joints (thorax rotation, elbow extension and wrist flexion). The second is the
muscular torque effect of the shoulder internal rotation (IR) torque on
generating IR angular velocity. In particular, the centrifugal force-induced
elbow extension motion, which was the greatest contributor among individual joint
contributions, was caused primarily by the angular velocity-dependent forces
associated with the humerus, thorax, and trunk rotations. Our study also found
that a compensatory mechanism was achieved by the negative and positive
contributions of the muscular torque components. The current IVA is helpful to
understand how the rapid throwing arm movement is determined by the dynamic
coupling mechanism.
PMID- 28692837
TI - Influence of gait mode and body orientation on following a walking avatar.
AB - Regulating distance with a moving object or person is a key component of human
movement and of skillful interpersonal coordination. The current set of
experiments aimed to assess the role of gait mode and body orientation on
distance regulation using a cyclical locomotor tracking task in which
participants followed a virtual leader. In the first experiment, participants
moved in the backward-forward direction while the body orientation of the virtual
leader was manipulated (i.e., facing towards, or away from the follower), hence
imposing an incongruence in gait mode between leader and follower. Distance
regulation was spatially less accurate when followers walked backwards.
Additionally, a clear trade-off was found between spatial leader-follower
accuracy and temporal synchrony. Any perceptual effects were overshadowed by the
effect of one's gait mode. In the second experiment we examined lateral
following. The results suggested that lateral following was also constrained
strongly by perceptual information presented by the leader. Together, these
findings demonstrated how locomotor tracking depends on gait mode, but also on
the body orientation of whoever is being followed.
PMID- 28692838
TI - Low ADAMTS13 levels are associated with venous thrombosis risk in women.
PMID- 28692839
TI - Rivaroxaban versus warfarin in the prevention of post-thrombotic syndrome.
AB - INTRODUCTION: Post-thrombotic syndrome (PTS) is a chronic complication of deep
vein thrombosis (DVT) that affects 20% to 50% of DVT patients. Standard DVT
treatment included vitamin K antagonists (usually warfarin) with low-molecular
weight heparin in the initial period. In recent years, direct oral anticoagulants
(DOAC) were introduced. We aimed to investigate the influence of rivaroxaban and
warfarin on PTS development. METHODS: Consecutive patients treated for DVT were
included, 39 were treated with warfarin and 61 with rivaroxaban. We assessed
symptoms and signs of PTS and calculated Villalta score 23months (median) after
acute DVT diagnosis. Differences between patients treated with rivaroxaban and
warfarin were investigated. RESULTS: Patients in the rivaroxaban group had a
lower prevalence of PTS than those treated with warfarin (25% vs. 49%, p=0.013).
Logistic regression showed odds ratio of 2.9 (1.2-6.8, p=0.014) for PTS
development in warfarin group compared to rivaroxaban group. When adjusted for
other variables, the odds ratio was 3.5 (1.1-11.0, p=0.035). CONCLUSIONS:
Treatment of DVT with rivaroxaban might be associated with a lower risk for PTS
development. A larger randomized trial would be needed for stronger evidence.
PMID- 28692840
TI - Normal pregnancy is associated with an increase in thrombin generation from the
very early stages of the first trimester.
AB - BACKGROUND: Pregnancy is a hypercoagulable state associated with an increased
risk of venous thrombosis, which begins during the first trimester, but the exact
time of onset is unknown. Thrombin generation, a laboratory marker of thrombosis
risk, increases during normal pregnancy but it is unclear exactly how early this
increase occurs. METHODS: We assessed thrombin generation by Calibrated Automated
Thrombography in women undergoing natural cycle in vitro fertilization, who
subsequently gave birth at term following a normal pregnancy (n=22). Blood
samples were taken just prior to conception and repeated five times during very
early pregnancy, up to Day 59 estimated gestation. RESULTS: Mean Endogenous
Thrombin Potential (ETP), peak thrombin generation and Velocity Index (VI)
increased significantly from pre-pregnancy to Day 43 gestation (p=0.024-0.0004).
This change persisted to Day 59 gestation. The mean of the percentage change from
baseline, accounting for inter-individual variation, in ETP, peak thrombin and VI
increased significantly from pre-pregnancy to Day 32 gestation (p=0.0351-<0.0001)
with the mean increase from baseline persisting to Day 59 gestation. CONCLUSION:
Thrombin generation increases significantly during the very early stages of
normal pregnancy when compared to the pre-pregnancy state. The increased risk of
venous thrombosis therefore likely begins very early in a woman's pregnancy,
suggesting that women considered clinically to be at high thrombotic risk should
start thromboprophylaxis as early as possible after a positive pregnancy test.
PMID- 28692841
TI - Heparins inhibit the endothelial pro-thrombotic features induced by tumor cells.
PMID- 28692842
TI - PK-driven prophylaxis versus standard prophylaxis: When a tailored treatment may
be a real and achievable cost-saving approach in children with severe hemophilia
A.
AB - BACKGROUND: Prophylaxis is the gold standard for the treatment of children with
severe hemophilia. In the last years a new approach to prophylaxis based on
annual bleeding rate (ABR), pharmacokinetics (PK) and lifestyle of each patient
has begun to be adopted in hemophilia treatment. AIM: Aim of our observational
retrospective study was to evaluate whether in a group of children with severe
hemophilia A (HA) a tailored approach may be used to replace standard therapy,
reducing costs. METHODS: PK evaluation was carried out in six hemophiliac
children followed at our Hemophilia Center, and already receiving recombinant
factor VIII (rFVIII) on prophylaxis, using a computing program (MyPKfit(r)).
Bayesian curve was created for each child and tailored prophylaxis was estimated
considering a trough level of 1%. RESULTS: The weekly frequency of infusions was
reduced in one patient, while it was slightly increased in three children. As to
the remaining children, only the dosage was changed. Scheduled follow-up revealed
a complete adherence to treatment, a reduction of bleeds using PK-regimen and a
general improvement in the quality of life. The comparison between the direct and
indirect costs of treatment during standard and PK-driven prophylaxis showed a
total saving of ? 54,797.40 (-10.67%) in case of tailored prophylaxis.
CONCLUSION: A therapeutic approach based on PK and clinical characteristics of
each patient may change standard treatment. Based on our results, tailored
prophylaxis could be an effective option for children with HA reducing costs.
PMID- 28692843
TI - The mechanical behavior of TiNbSn alloys according to alloying contents, cold
rolling and aging.
AB - The present study is focused on mechanical properties that result from cold
rolling and aging treatments applied to TiNbSn alloys comprising different Nb
(35% and 42%) and Sn (0% and 2.5%) contents. The alloys were arc melted,
homogenized, solubilized, cold rolled and aged at 400 degrees C for different
aging times. A set of characterization tests performed, included microstructural
analysis, X-ray diffraction, microhardness, tensile tests and fracture analysis.
The alloys contained all three beta, alpha" and omega phases after cold rolling,
regardless of the alloying content. The solid solution effect led to changes in
the alloys' mechanical behavior. Furthermore, the alloys presented alpha phase
precipitation, and it led to a peak-aged stage after different aging times due to
the Nb content. The alloys containing 42% and 35% Nb content reached the peak
aged stage within 48 and 72h, respectively. The alpha phase precipitation in the
alloys at peak-aged stage increased the hardness, tensile strength and elastic
modulus of the alloys; however, it also caused ductility to decrease. The fine
dispersed precipitates of the alpha phase generated small and shallow dimples,
which are a characteristic fracture micromechanism of peak-aged alloys.
PMID- 28692844
TI - Comparative bonding ability to dentin of a universal adhesive system and monomer
conversion as functions of extended light curing times and storage.
AB - OBJECTIVES: The purpose of this in vitro study was to evaluate the bonding
ability and monomer conversion of a universal adhesive system applied to dentin
as functions of different curing times and storage. The results were compared
among a variety of commercial adhesives. MATERIALS AND METHODS: Flat superficial
dentin surfaces were exposed on human molars and assigned into one of the
following adhesives (n = 15): total-etch Adper Single Bond 2 (SB) and Optibond
Solo Plus (OS), self-etch Optibond All in One (OA) and Clearfil SE Bond (CSE),
and Scotchbond Universal Adhesive in self-etch mode (SU). The adhesives were
applied following the manufacturers' instructions and cured for 10, 20, or 40s.
Specimens were processed for the microtensile bond strength (uTBS) test in
accordance with the non-trimming technique and tested after 24h and 2 years. The
fractured specimens were classified under scanning electron microscopy (SEM).
Infrared (IR) spectra were obtained and monomer conversion (%) was calculated by
comparing the aliphatic-to-aromatic IR absorption peak ratio before and after
polymerization (n=5). Data were analyzed by 2-way ANOVA/Tukey's tests (alpha =
0.05). RESULTS: At 24-h evaluation, OA and CSE presented similar bond strength
means irrespective of the curing time, whereas SB and SU exhibited significantly
higher means when cured for 40s as did OS when cured for 20 or 40s (p < 0.05). At
2-year evaluation, only OA exhibited significantly higher bond strength when
cured for 20 and 40s (p < 0.05). When the evaluation times were compared, OA also
exhibited the same bonding ability when cured for longer periods of time (20 and
40s). All of the adhesives tested exhibited significantly lower monomer
conversion when photoactivated according to the manufacturers' instructions
(10s). CONCLUSIONS: Higher monomer conversions obtained with longer light
exposure allow only higher immediate bond strength for most of the adhesives
tested. After 2-year storage, only the self-etching adhesive Optibond All-In-One
exhibited the same bonding ability when cured for longer periods of time.
PMID- 28692845
TI - Constitutive modeling of jugular vein-derived venous valve leaflet tissues.
AB - Venous valve tissues, though used in vein reconstruction surgeries and
bioprosthetic valves with moderate success, have not been extensively studied
with respect to their structure. Their inherent anisotropic, non-linear behavior
combined with severe diseases which affect veins, such as chronic venous
insufficiency, warrant understanding the structure and material behavior of these
tissues. Hence, before any bioprosthetic grafts may be used in place of tissues,
it is of the utmost importance to understand the mechanical and structural
properties of these tissues as this may lead to higher success rates for valve
replacement surgeries. The longevity of the bioprosthetics may also increase if
the manufactured grafts behave the same as native valves. Building on the scant
information about the uniaxial and biaxial mechanical properties of jugular
venous valves and wall tissues from previous studies, the current focus of our
investigation lies in understanding the material behavior by establishing a
phenomenological strain energy-based constitutive relation for the tissues. We
used bovine veins to study the behavior of valve leaflet tissue and adjoining
wall tissue (from the proximal and distal ends of the veins) under different
biaxial testing protocols. We looked at the behavior of numerical partial
derivatives of the strain energy to select a suitable functional form for the
strain energy for wall and valve tissues. Using this strain energy descriptor, we
determined the Cauchy stress and compared it with experimental results under
additional sets of displacement-controlled biaxial testing protocols to find
material specific model parameters by the Powell's method algorithm. Results show
that whereas wall tissue strain energy can be explained using a polynomial non
linear function, the valve tissue, due to higher non-linearities, requires an
exponential function. This study may provide useful information for the primary
stages of bioprosthetic designs and replacement surgeries and may support future
studies investigating structural models. It may also support the study of
valvular diseases by providing a way to understand material properties and
behavior and to form a continuum model when required for numerical analyses and
computational simulations.
PMID- 28692846
TI - Development of screen-printed electrode based immunosensor for the detection of
HER2 antigen in human serum samples.
AB - In this study, an immunosensor based on screen-printed electrode (SPE) has been
developed for the detection of Human Epidermal Growth Factor Receptor-2 (HER2)
antigen. The SPEs were fabricated and a sandwich enzyme linked immunosorbent
assay (ELISA) format was followed for the construction of the immunosensor. The
capture antibody (mouse anti-human ErbB2) was coated onto the electrode surface
without any prior surface modification, followed by the addition of recombinant
human HER2 antigen. Biotinylated goat anti-human ErbB2 was used as the detection
antibody which was linked to streptavidin conjugated horseradish peroxidase
(HRP). 3,3',5,5'-tetramethylbenzidine (TMB) was used as the substrate. The redox
reaction was measured using cyclic voltammetry at scan rate of 50mV/s for the
quantification of the antigen in solution. The biotin-avidin chemistry enabled
the accurate detection of the antigen in nanogram levels. The amperometric signal
obtained increased linearly with increase in the HER2 concentration and two-fold
linear range was obtained between 5ng/ml-20ng/ml and 20-200ng/ml respectively.
The limit of detection (LOD) and the limit of quantification (LOQ) of this
immunosensor were found to be 4ng/ml and 5ng/ml respectively. The detection of
HER2 in the serum samples of invasive and non-invasive breast cancer patients has
been realized.
PMID- 28692847
TI - Microbial metabolites are associated with a high adherence to a Mediterranean
dietary pattern using a 1H-NMR-based untargeted metabolomics approach.
AB - The study of biomarkers of dietary patterns including the Mediterranean diet
(MedDiet) is scarce and could improve the assessment of these patterns. Moreover,
it could provide a better understanding of health benefits of dietary patterns in
nutritional epidemiology. We aimed to determine a robust and accurate biomarker
associated with a high adherence to a MedDiet pattern that included dietary
assessment and its biological effect. In this cross-sectional study, we included
56 and 63 individuals with high (H-MDA) and low (L-MDA) MedDiet adherence
categories, respectively, all from the Prevencion con Dieta Mediterranea trial. A
1H-NMR-based untargeted metabolomics approach was applied to urine samples.
Multivariate statistical analyses were conducted to determine the metabolite
differences between groups. A stepwise logistic regression and receiver operating
characteristic curves were used to build and evaluate the prediction model for H
MDA. Thirty-four metabolites were identified as discriminant between H-MDA and L
MDA. The fingerprint associated with H-MDA included higher excretion of proline
betaine and phenylacetylglutamine, among others, and decreased amounts of
metabolites related to glucose metabolism. Three microbial metabolites -
phenylacetylglutamine, p-cresol and 4-hydroxyphenylacetate - were included in the
prediction model of H-MDA (95% specificity, 95% sensitivity and 97% area under
the curve). The model composed of microbial metabolites was the biomarker that
defined high adherence to a Mediterranean dietary pattern. The overall metabolite
profiling identified reflects the metabolic modulation produced by H-MDA. The
proposed biomarker may be a better tool for assessing and aiding nutritional
epidemiology in future associations between H-MDA and the prevention or
amelioration of chronic diseases.
PMID- 28692848
TI - Modifications of fatty acids profile, lipid peroxidation and antioxidant capacity
in raw and cooked rabbit burgers added with ginger.
AB - Effects of ginger powder were evaluated on fatty acid (FA) profile, lipid
peroxidation (TBARS) and antioxidant capacity (ABTS, DPPH and FRAP) of rabbit
burgers. Burgers were manufactured as control samples (only meat) and two
additions of ginger powder (1% and 2%) and stored raw at 4 degrees C for 7days.
At day 1, 4 and 7 of storage burgers were analysed both as raw and cooked. Ginger
powder affected all the tested parameters; both PUFAomega3 and PUFAomega6 were
incremented in raw and cooked samples leading to decreased atherogenicity and
thrombogenicity indexes and increased hypo/hypercholesterolemic index and
peroxidability index. Lipid peroxidation values of raw and cooked burgers added
with ginger were lower than control burgers, at the same time, ABTS, DPPH and
FRAP values were incremented by the addition of ginger powder. The results
obtained demonstrate the antioxidant capacity of ginger powder as rabbit meat
products additive and highlight the capacity of this spice to maintain its
characteristics after burgers' cooking.
PMID- 28692849
TI - Designing healthier comminuted meat products: Effect of dietary fibers on water
distribution and texture of a fat-reduced meat model system.
AB - Development of healthier meat products is needed to meet consumers' request. The
effects of dietary fiber addition on the water distribution, water binding
capacity (WBC), and textural properties of a fat-reduced model meat system
enriched with inulin, cellulose, carboxymethyl cellulose (CMC), chitosan, pectin,
respectively, were investigated in this study. The fibers were incorporated in
powder form to constitute 2% (w/w) of the meat batter. In general, fiber
enrichment resulted in significant lower cooking loss and improved WBC, while the
impact on texture was dependent on the specific dietary fiber. Low-field NMR
relaxometry revealed that chitosan impacted the heating-induced changes in water
distribution differently from other fibers and that CMC had a higher capability
to counteract the impact of heat-induced protein denaturation on water expulsion
than the other fiber types. It is anticipated that this knowledge is useful in
the development of novel strategies where dietary fiber enrichment is optimized
to promote specific and desired technological attributes of healthy meat
products.
PMID- 28692850
TI - The impact of homogeniser speed, dispersing aggregate size and centrifugation on
particle size analyses of pork as a measure of myofibrillar fragmentation.
AB - Particle size analysis has been proposed as a measure of myofibrillar
fragmentation resulting from post-mortem proteolysis in meat. The aim of this
study was to examine the effect of homogenisation speed, dispersing aggregate
size and centrifugation on particle size characteristics of pork loin. Particle
size characteristics were significantly (P<=0.023) greater for samples aged 2
than 8d for all but the 80 and 90% quantiles. Differentiation with ageing was
only achieved when homogenised at 11,000rpm using the smaller dispersing
aggregate (9 vs 13mm rotor diameters). Centrifugation had no effect on particle
size characteristics. Significant correlations with MFI (r=-0.40 to -0.81,
P<0.001) and shear force in meat aged at 3.7 degrees C (r=0.36-0.47; P<0.001)
were observed. Weak or inconsistent correlations with shear force suggest
adoption of particle size analyses as a method of tenderness classification
unlikely. Rather, value lies in the detailed profiles of particle size
distributions with meat ageing.
PMID- 28692851
TI - A simple device to convert a small-animal PET scanner into a multi-sample tissue
and injection syringe counter.
AB - INTRODUCTION: We describe a simple fixture that can be added to the imaging bed
of a small-animal PET scanner that allows for automated counting of multiple
organ or tissue samples from mouse-sized animals and counting of injection
syringes prior to administration of the radiotracer. The combination of imaging
and counting capabilities in the same machine offers advantages in certain
experimental settings. METHODS: A polyethylene block of plastic, sculpted to mate
with the animal imaging bed of a small-animal PET scanner, is machined to receive
twelve 5-ml containers, each capable of holding an entire organ from a mouse
sized animal. In addition, a triangular cross-section slot is machined down the
centerline of the block to secure injection syringes from 1-ml to 3-ml in size.
The sample holder is scanned in PET whole-body mode to image all samples or in
one bed position to image a filled injection syringe. Total radioactivity in each
sample or syringe is determined from the reconstructed images of these objects
using volume re-projection of the coronal images and a single region-of-interest
for each. We tested the accuracy of this method by comparing PET estimates of
sample and syringe activity with well counter and dose calibrator estimates of
these same activities. RESULTS: PET and well counting of the same samples gave
near identical results (in MBq, R2=0.99, slope=0.99, intercept=0.00-MBq). PET
syringe and dose calibrator measurements of syringe activity in MBq were also
similar (R2=0.99, slope=0.99, intercept=- 0.22-MBq). CONCLUSION: A small-animal
PET scanner can be easily converted into a multi-sample and syringe counting
device by the addition of a sample block constructed for that purpose. This
capability, combined with live animal imaging, can improve efficiency and
flexibility in certain experimental settings.
PMID- 28692852
TI - Novel collection method for volatile organic compounds (VOCs) from dogs.
AB - Host derived chemical cues are an important aspect of arthropod attraction to
potential hosts. Host cues that act over longer distances include CO2, heat, and
water vapor, while cues such as volatile organic compounds (VOCs) act over closer
distances. Domestic dogs are important hosts for disease cycles that include dog
heartworm disease vectored by mosquitoes, however the host VOCs utilized by
vectors are not well known. Herein we present a novel method that sampled VOCs
from a dog host. A Tenax TD stainless steel tube was held near a dog's fur and
skin, which collected VOCs that were later desorbed and tentatively identified
using a gas chromatograph-mass spectrospectrometer (GC-MS). Background air
chemicals were subtracted from the dog sample, resulting in 182 differentiated
compounds, a majority of which were identified by ionization fragmentation
patterns. Four dogs were sampled and shared 41 of the identified chemicals. VOCs
were representative of aliphatics, aromatics, aldehydes, alcohols and carboxylic
acids. This chemical characterization method has the potential to identify both
individuals and breeds of dogs in addition to other potential uses such as
disease diagnosis.
PMID- 28692853
TI - Receiver calibration and the nonlinearity parameter measurement of thick solid
samples with diffraction and attenuation corrections.
AB - This paper presents analytical and experimental techniques for accurate
determination of the nonlinearity parameter (beta) in thick solid samples. When
piezoelectric transducers are used for beta measurements, the receiver
calibration is required to determine the transfer function from which the
absolute displacement can be calculated. The measured fundamental and second
harmonic displacement amplitudes should be modified to account for beam
diffraction and material absorption. All these issues are addressed in this study
and the proposed technique is validated through the beta measurements of thick
solid samples. A simplified self-reciprocity calibration procedure for a
broadband receiver is described. The diffraction and attenuation corrections for
the fundamental and second harmonics are explicitly derived. Aluminum alloy
samples in five different thicknesses (4, 6, 8, 10, 12cm) are prepared and beta
measurements are made using the finite amplitude, through-transmission method.
The effects of diffraction and attenuation corrections on beta measurements are
systematically investigated. When diffraction and attenuation corrections are all
properly made, the variation of beta between different thickness samples is found
to be less than 3.2%.
PMID- 28692854
TI - Laser-induced ultrasonic waveform derivation and transition from a point to a
homogeneous illumination of a plate.
AB - Ultrasound modeling, being an established practice, is used to study the
fundamentals of light-matter interactions. Although much has been published on
the matter, pressure and thermal expansion induction mechanisms in laser
ultrasonics have rarely been combined, as they should, in a single ultrasonic
source while the effects of its size variation have only been shown to a limited
extent. In the paper, we unite these light-matter interaction mechanisms, with
inclusion of lateral optical forces, into a single laser-stimulated source as it
is observed in nature. With a laser pulse as a manipulable source, we simulate
the multifaceted workings of light-matter interactions by exposing the distinct
transients originating from different source localities as generated by different
induction mechanisms. We also present a transition of simulated ultrasonic
waveforms in the epicentral point on the surface of a solid plate opposite from
the source while it is expanded from a point to a quasi-limitless extent for
pressure and thermal expansion generation regimes. The model utilizes geometric
probability theory together with Huygens' superposition principle and temporal
convolutions to construct the desired waveforms out of individual Green's
functions. We show how the ultrasound generation regimes stem out of a single
source and how its size together with energy and momentum transfers during the
light-matter interactions affect the induced ultrasonic transients.
PMID- 28692855
TI - Recuperation of slow walking in de novo Parkinson's disease is more closely
associated with increased cadence, rather than with expanded stride length.
AB - INTRODUCTION: Gait characteristics in the early stages of Parkinson's disease
(PD) have been less investigated so far. Moreover, the levodopa effect on gait in
early PD remains to be further elucidated. We prospectively designed the study to
examine gait dynamics and effect of dopaminergic treatment in patients with de
novo PD. METHODS: Spatiotemporal parameters were measured in healthy controls and
drug naive patients with PD, using computerized analysis with GAITRite system
during usual gait. In PD group, motor symptoms and gait parameters were examined
in both drug naive and levodopa 100mg trial conditions. RESULTS: Twenty four de
novo PD patients and 27 healthy controls (matched for age, sex, and height) were
selected for the study. Compared with the controls, patients with de novo PD
showed the decrease in stride length, in both Med-OFF and Med-ON conditions.
Notably, drug naive patients with PD demonstrated slow walking velocity, whereas
those with levodopa administration exhibited the increase of cadence by
shortening stride time, which resulted in the improvement of gait speed. In
addition, the stride length (gait hypokinesia) correlated with postural
instability and gait difficulty subscore, but not with tremor, rigidity,
bradykinesia, or total motor score. CONCLUSION: As a compensatory mechanism of
slow walking, we found that the increment in cadence (frequency) is more
important than the increment in stride length (amplitude) in gait dynamics in de
novo PD. Additionally, the results may indicate that gait hypokinesia in PD could
be regarded as one of axial symptoms.
PMID- 28692856
TI - Nutrient scavenging and energy management: acclimation responses in nitrogen and
sulfur deprived Chlamydomonas.
AB - Photosynthetic organisms have evolved to modulate their metabolism to accommodate
the highly dynamic light and nutrient conditions in nature. In this review we
discuss ways in which the green alga Chlamydomonas reinhardtii acclimates to
nitrogen and sulfur deprivation, conditions that would limit the anabolic use of
excitation energy because of a markedly reduced capacity for cell growth and
division. Major aspects of this acclimation process are stringently regulated and
involve scavenging the limited nutrient from internal and external sources, and
the redirection of fixed carbon toward energy storage (e.g. starch, oil).
However, photosynthetic organisms have also evolved mechanisms to dissipate
excess absorbed light energy, and to eliminate potentially dangerous energetic
electrons through the reduction of O2 and H+ to H2O; this reduction can occur
both through photosynthetic electron transport (e.g. Mehler reaction,
chlororespiration) and mitochondrial respiration. Furthermore, algal cells likely
exploit other energy management pathways that are currently not linked to
nutrient limitation responses or that remain to be identified.
PMID- 28692857
TI - Modelling and extraction of pulsatile radial distension and compression motion
for automatic vessel segmentation from video.
AB - Identification of vascular structures from medical images is integral to many
clinical procedures. Most vessel segmentation techniques ignore the
characteristic pulsatile motion of vessels in their formulation. In a recent
effort to automatically segment vessels that are hidden under fat, we motivated
the use of the magnitude of local pulsatile motion extracted from surgical
endoscopic video. In this article we propose a new approach that leverages the
local orientation, in addition to magnitude of motion, and demonstrate that the
extended computation and utilization of motion vectors can improve the
segmentation of vascular structures. We implement our approach using four
alternatives to magnitude-only motion estimation by using traditional optical
flow and by exploiting the monogenic signal for fast flow estimation. Our
evaluations are conducted on both synthetic phantoms as well as two real
ultrasound datasets showing improved segmentation results with negligible change
in computational performance compared to the previous magnitude only approach.
PMID- 28692858
TI - Calcium signatures and signaling events orchestrate plant-microbe interactions.
AB - Calcium (Ca2+) acts as an essential second messenger connecting the perception of
microbe signals to the establishment of appropriate immune and symbiotic
responses in plants. Accumulating evidence suggests that plants distinguish
different microorganisms through plasma membrane-localized pattern recognition
receptors. The particular recognition events are encoded into Ca2+ signatures,
which are sensed by diverse intracellular Ca2+ binding proteins. The Ca2+
signatures are eventually decoded to distinct downstream responses through
transcriptional reprogramming of the defense or symbiosis-related genes. Recent
observations further reveal that Ca2+-mediated signaling is also involved in
negative regulation of plant immunity. This review is intended as an overview of
Ca2+ signaling during immunity and symbiosis, including Ca2+ responses in the
nucleus and cytosol.
PMID- 28692859
TI - An experimental study addressing the use of geoforensic analysis for the
exploitation of improvised explosive devices (IEDs).
AB - The use of geoforensic analysis in criminal investigations is continuing to
develop, with the diversification of analytical techniques, many of which are
semi-automated, facilitating prompt analysis of large sample sets at a relatively
low cost. Whilst micro-scale geoforensic analysis has been shown to assist
criminal investigations including homicide (Concheri et al., 2011 [1]), wildlife
crime (Morgan et al., 2006 [2]), illicit drug distribution (Stanley, 1992 [3]),
and burglary (Mildenhall, 2006 [4]), its application to the pressing
international security threat posed by Improvised Explosive Devices (IEDs) is yet
to be considered. This experimental study simulated an IED supply chain from the
sourcing of raw materials through to device emplacement. Mineralogy, quartz grain
surface texture analysis (QGSTA) and particle size analysis (PSA) were used to
assess whether environmental materials were transferred and subsequently
persisted on the different components of three pressure plate IEDs. The research
also addressed whether these samples were comprised of material from single or
multiple geographical provenances that represented supply chain activity nodes.
The simulation demonstrated that material derived from multiple activity nodes,
was transferred and persisted on device components. The results from the
mineralogy and QGSTA illustrated the value these techniques offer for the
analysis of mixed provenance samples. The results from the PSA, which produces a
bulk signature of the sample, failed to distinguish multiple provenances. The
study also considered how the environmental material recovered could be used to
generate information regarding the geographical locations the device had been in
contact with, in an intelligence style investigation, and demonstrated that
geoforensic analysis has the potential to be of value to international counter
IED efforts. It is a tool that may be used to prevent the distribution of large
quantities of devices, by aiding the identification of the geographical location
of key activity nodes.
PMID- 28692860
TI - 1H and 31P benchtop NMR of liquids and solids used in and/or produced during the
manufacture of methamphetamine by the HI reduction of pseudoephedrine/ephedrine.
AB - In this study, the use of benchtop NMR spectroscopy in the analysis of solids and
liquids used and/or produced during the HI reduction of pseudoephedrine was
evaluated. The study focused on identifying organic precursors and phosphorus
containing compounds used in and/or produced during the manufacturing process.
Samples taken from clandestine laboratories, where this synthesis process was
suspected of occurring, were also analysed and evaluated. Benchtop NMR was able
to distinguish between ephedrine, pseudoephedrine and methamphetamine as the free
base and hydrochloride salt. This technique was also effective at identifying and
distinguishing between phosphorus containing compounds used and/or produced
during the manufacture of methamphetamine. Benchtop NMR was also determined to be
effective at analysing samples from suspected clandestine laboratories.
PMID- 28692861
TI - Getting to the elephants: Gesture and preschoolers' comprehension of route
direction information.
AB - During early childhood, children find spatial tasks such as following novel route
directions challenging. Spatial tasks place demands on multiple cognitive
processes, including language comprehension and memory, at a time in development
when resources are limited. As such, gestures accompanying route directions may
aid comprehension and facilitate task performance by scaffolding cognitive
processes, including language and memory processing. This study examined the
effect of presenting gesture during encoding on spatial task performance during
early childhood. Three- to five-year-olds were presented with verbal route
directions through a zoo-themed spatial array and, depending on assigned
condition (no gesture, beat gesture, or iconic/deictic gesture), accompanying
gestures. Children presented with verbal route directions accompanied by a
combination of iconic (pantomime) and deictic (pointing) gestures verbally
recalled more than children presented with beat gestures (rhythmic hand
movements) or no gestures accompanying the route directions. The presence of
gesture accompanying route directions similarly influenced physical route
navigation, such that children presented with gesture (beat, pantomime, and
pointing) navigated the route more accurately than children presented with no
gestures. Across all gesture conditions, location information (e.g., the penguin
pond) was recalled more than movement information (e.g., go around) and
descriptive information (e.g., bright red). These findings suggest that speakers'
gestures accompanying spatial task information influence listeners' recall and
task performance.
PMID- 28692862
TI - Are Pakistan's ambiguous blasphemy laws enabling vigilantism?
PMID- 28692863
TI - Identification of genetic correlates of response to Risperidone: Findings of a
multicentric schizophrenia study from India.
AB - Risperidone is most commonly used as an antipsychotic in India for treatment of
schizophrenia. However, the response to treatment with risperidone is affected by
many factors, genetic factors being one of them. So, we attempted to evaluate the
association between dopamine D2 (DRD2) receptor, serotonergic (5HT2A) receptor
and CYP2D6 gene polymorphisms and response to treatment with risperidone in
persons with schizophrenia from North India. It was a multicentric 12-weeks
prospective study, undertaken in patients diagnosed with schizophrenia according
to International Classification of Diseases 10th revision, Diagnostic Criteria
for Research module (ICD-10 DCR). Patients were treated with incremental dosages
of risperidone. Nine gene polymorphisms from three genes viz. DRD2, 5-HT2A and
CYP2D6 along with socio-demographical and clinical variables were analyzed to
ascertain the association in response to risperidone treatment. The change in the
Positive and Negative Syndrome Scale (PANSS) was used to measure the outcome.
Significant differences in the frequencies of single nucleotide proteins (SNPs)
rs180498 (Taq1D) and rs 6305 (C516T) polymorphisms were found amongst the groups
defined according to percent decline in PANSS. The CYP2D6*4 polymorphism differed
significantly when drop outs were excluded from analysis. Presence of DRD2 Taq 1
D2D2 and 5-HT2A C516T CT genotypes in patients were more likely to be associated
with non-response to risperidone. Ser311Cys (rs1801028) mutation was absent in
the North Indian patients suffering from schizophrenia.
PMID- 28692864
TI - Serum IL-10, IL-17 and IL-23 levels as "bioumoral bridges" between dyslipidemia
and atopy.
AB - BACKGROUND: Although several studies suggest a possible link between dyslipidemia
and atopy, literature findings are still unclear. OBJECTIVE: The aim of the study
was to investigate the relationship between dyslipidemia and atopy in a pediatric
population affected by dyslipidemia or dyslipidemia/atopic predisposition.
MATERIALS AND METHODS: Children with dyslipidemia, dyslipidemia and atopy as well
as healthy children were recruited. Serum total IgE, IL-10, IL-17, and IL-23
levels as well as fasting lipid values (total cholesterol, LDL, HDL and
triglycerides) were performed on all enrolled children. RESULTS: The present
study evaluated 23 patients affected by dyslipidemia, 26 patients affected by
atopy and dyslipidemia and, 22healthy children. Serum total IgE levels
significantly related also with serum cholesterol levels: positively with total
cholesterol (p<0.05), LDL (p<0.05), and tryglicerides (p<0.001), but negatively
with HDL (p<0.05). Serum levels of IL-10 were lower in children with atopy and
dyslipidemia than patients with dyslipidemia (p<0.001). Serum IL-10 levels
significantly related also with serum cholesterol levels: negatively with total
cholesterol (p<0.001), LDL (p<0.05), and triglycerides (p<0.05), but positively
with HDL (p<0.05). Serum IL-17 and IL-23 levels showed the same trend. They were
significantly higher in children with atopy and dyslipidemia than patients with
dyslipidemia (p<0.001). In particular, serum IL-17 and IL-23 values positively
correlated with serum total IgE levels (p<0.05); serum total cholesterol levels
(p<0.001); serum LDL levels (p<0.001); serum triglycerides levels (p<0.05).
Although not statistically significant, an inverse correlation has been noted
between serum IL-17, IL-23 and HDL levels. CONCLUSIONS: These findings support
the notion that dyslipidemia and atopic predisposition share the same immune
pathways as well as they offer new insights in the complex crosstalk between
hyperlipidemia and atopy.
PMID- 28692865
TI - Live cell confocal laser imaging studies on the nuclear behavior during meiosis
and ascosporogenesis in Morchella importuna under artificial cultivation.
AB - The commercial production of Morchella mushrooms, especially M. importuna, has
been realized since 2012 in China, which facilitates the fundamental studies of
Morchella spp. In this paper, the cytological characteristics at three stages of
ascocarpic development and the nuclear behavior during meiosis and
ascosporogenesis in cultivated strain M. importuna 1# was visualized by confocal
laser scanning microscopy. The results suggested that the strain sporulated at
sporulation stage of ascocarpic development. A total of six nuclear divisions
typically took place during ascosporogenesis. The first and second divisions were
meiotic in which the single diploid nucleus divided into four haploid nuclei. The
subsequent mitosis gave rise to eight nuclei, and eight incipient ascospores with
one nucleus in each spore were formed after spore delimitation in the clavate
ascus. Then, the nucleus in most of the young ascospore underwent three
successive mitoses producing 6-8 haploid nuclei in each mature spore, and thus
the multinucleate ascospores in each ascus were all homokaryons. To the best of
our knowledge, this is the first dynamic tracing study of nuclear behavior during
meiosis and ascosporogenesis in cultivated morels, and the spore delimitation
time is also the first report. The study will be beneficial for the genetics
study and strain breeding of Morchella mushrooms.
PMID- 28692866
TI - Linking fungal-bacterial co-occurrences to soil ecosystem function.
AB - Fungi and bacteria are major players in soil biogeochemical cycles, however, most
studies linking soil processes to microbial function ignore the potential role of
interactions between these groups. A small number of studies have used
correlation network analyses to investigate fungal-bacterial co-occurrences in
soil, and revealed differences, as well as overlaps, in the ecosystem roles of
these groups. These results contradict the view that fungi and bacteria are two
distinct functional groups which can be studied in isolation. A more
comprehensive understanding of the interplay between soil properties,
biogeochemical cycles and the interactions between fungi and bacteria will be an
important step towards improving the prediction and management of soil ecosystem
services.
PMID- 28692867
TI - Sulfate transport kinetics and toxicity are modulated by sodium in aquatic
insects.
AB - The salinization of freshwater ecosystems is emerging as a major ecological
issue. Several anthropogenic causes of salinization (e.g. surface coal mining,
hydro-fracking, road de-icing, irrigation of arid lands, etc.) are associated
with biodiversity losses in freshwater ecosystems. Because insects tend to
dominate freshwater ecology, it is important that we develop a better
understanding of how and why different species respond to salinity matrices
dominated by different major ions. This study builds upon previous work
demonstrating that major ion toxicity to the mayfly Neocloeon triangulifer was
apparently due to the ionic composition of water rather than specific
conductance. Synthetic waters with low Ca:Mg ratios and high SO4:Na ratios
produced toxicity, whereas waters with higher Ca:Mg ratios and lower SO4:Na
ratios were not toxic to mayflies at comparable conductivities. Here we used a
radiotracer approach to show that Mg did not competitively exclude Ca uptake at
environmentally realistic ratios in 4 aquatic insect species. We characterized
SO4 uptake kinetics in 5 mayflies and assessed the influence of different ions on
SO4 uptake. Dual label experiments show an inverse relationship between SO4 and
Na transport rates as SO4 was held constant and Na was increased, suggesting that
Na (and not Cl or HCO3) is antagonistic to SO4 transport. Based on this
observation, we tested the hypothesis that increasing Na would protect against
SO4 induced toxicity in a Na-dependent manner. Increasing Na from 0.7 to 10.9mM
improved 96-h survivorship associated with 20.8mM SO4 from 44% to 73% in a
concentration dependent manner. However, when Na reached 21.8mM, survivorship
decreased to 16%, suggesting that other interactive effects of major ions caused
toxicity under those conditions. Thus, the combination of elevated sulfate and
low sodium commonly observed in streams affected by mountaintop coal mining has
the potential to cause toxicity in sensitive aquatic insects. Overall, it is
important that we develop a better understanding of major ion toxicity to
effectively mitigate and protect freshwater biodiversity from salinization.
PMID- 28692868
TI - Single and mixture impacts of two pyrethroids on damselfly predatory behavior and
physiological biomarkers.
AB - Direct mortality due to toxicity of single pesticide exposure along a
concentration gradient, while the most common, is only one important parameter
for assessing the effects of pesticide contamination on aquatic ecosystems. Sub
lethal toxicity can induce changes in an organism's behavior and physiology that
may have population-level ramifications and consequences for ecosystem health.
Additionally, the simultaneous detection of multiple contaminants in monitored
watersheds stresses the importance of gaining a greater understanding of the
toxicities of combined exposures, particularly at low, environmentally relevant
concentrations. Using larvae of the Azure Damselfly (Coenagrion puella), we
conducted a combined exposure investigation of two widely-used pyrethroid
insecticides presumed to share the same neurotoxic mechanism of action, and
estimated their effect on predatory ability, mobility and three physiological
biomarkers (Glutathione S-transferase; GST, respiratory electron transport
system; ETS, and malondialdehyde; MDA). Deltamethrin exposure (0.065MUg/L and
0.13MUg/L) was found to reduce the predatory ability, but it did not affect the
larvae's mobility. Esfenvalerate exposure (0.069MUg/L and 0.13MUg/L), on the
other hand, induced no significant changes in predatory ability or mobility. The
decrease in predatory ability after the combination exposure (0.067MUg/L
deltamethrin and 0.12MUg/L esfenvalerate) did not significantly differ from the
impact of the single deltamethrin exposures. Glutathione-S-transferase was
induced after single esfenvalerate exposure and the lower deltamethrin
concentration exposure, but seemingly inhibited after exposure to the higher
concentration of deltamethrin as well as the combination of both pyrethroids. Our
data indicate that sub-lethal exposure to deltamethrin reduces predatory ability
and suggest that sub-lethal combined exposure to deltamethrin and esfenvalerate
inhibits the GST detoxification pathway. These effects can eventually result in a
lower emergence of adults from contaminated ponds.
PMID- 28692869
TI - Phi-order spectrophotokinetic characterisation and quantification of trans-cis
oxyresveratrol reactivity, photodegradation and actinometry.
AB - A new Phi-order kinetic method was proposed in this study for the investigation
of trans-cis photoisomerization reaction of Oxyresveratrol (ORVT) subjected to
non-isosbestic irradiation. In ethanolic media, it has been proven that forward
(PhiA->Blambdairr) and reverse (PhiB->Alambdairr) reaction quantum yields were
dependent on the monochromatic irradiation wavelength according to sigmoid
patterns over the spectral ranges of their electronic absorption (260-360nm). An
11.4- and 6.6-fold increases were recorded for PhiB->Alambdairr and PhiA
>Blambdairr, respectively. The efficiencies of the former (PhiB->Alambdairr,
ranging between 2.3*10-2 and 26.3*10-2) were 33 to 60% smaller than those of the
respective PhiA->Blambdairr measured at the irradiation wavelengths selected.
Overall, between 57 and 97% degradation of the initial trans-ORVT was observed
under relatively weak light intensities, with the highest values recorded at the
longest wavelengths. These findings strongly recommend protection from light in
all situations of this biologically important phytomolecule that possesses
therapeutic value of interest to pharmaceutical applications. The Phi-order
kinetics also offered a simple way to develop a reliable actinometric method that
proved ORVT to be an efficient actinometer for the dynamic range 295-360nm. The
usefulness of Phi-order kinetics for the investigation and quantification of
phytoproducts' photodegradation was discussed.
PMID- 28692870
TI - Air-assisted liquid-liquid microextraction using floating organic droplet
solidification for simultaneous extraction and spectrophotometric determination
of some drugs in biological samples through chemometrics methods.
AB - An air assisted liquid-liquid microextraction by applying the solidification of a
floating organic droplet method (AALLME-SFOD) coupled with a multivariate
calibration method, namely partial least squares (PLS), was introduced for the
fast and easy determination of Atenolol (ATE), Propanolol (PRO) and Carvedilol
(CAR) in biological samples via a spectrophotometric approach. The analytes would
be extracted from neutral aqueous solution into 1-dodecanol as an organic
solvent, using AALLME. In this approach a low-density solvent with a melting
point close to room temperature was applied as the extraction solvent. The
emulsion was immediately formed by repeatedly pulling in and pushing out the
aqueous sample solution and extraction solvent mixture via a 10-mL glass syringe
for ten times. After centrifugation, the extractant droplet could be simply
collected from the aqueous samples by solidifying the emulsion at a lower than
the melting point temperature. In the next step, analytes were back extracted
simultaneously into the acidic aqueous solution. Derringer and Suich multi
response optimization were utilized for simultaneous optimizing the parameters of
three analytes. This method incorporates the benefits of AALLME and dispersive
liquid-liquid microextraction considering the solidification of floating organic
droplets (DLLME-SFOD). Calibration graphs under optimized conditions were linear
in the range of 0.30-6.00, 0.32-2.00 and 0.30-1.40MUg mL-1 for ATE, CAR and PRO,
respectively. Other analytical parameters were obtained as follows: enrichment
factors (EFs) were found to be 11.24, 16.55 and 14.90, and limits of detection
(LODs) were determined to be 0.09, 0.10 and 0.08MUg mL-1 for ATE, CAR and PRO,
respectively. The proposed method will require neither a highly toxic chlorinated
solvent for extraction nor an organic dispersive solvent in the application
process; hence, it is more environmentally friendly.
PMID- 28692871
TI - A highly sensitive and selective off-on fluorescent chemosensor for hydrazine
based on coumarin beta-diketone.
AB - A coumarin-based sensor C1, namely 3-acetoacetylcoumarin was designed,
synthesized and applied for hydrazine detection. Hydrazinolysis of the
chemosensor gives a fluorescent coumarin-pyrazole product C1-N2H4 [3-(3-methyl-1H
pyrazol-5-yl)coumarin], and thus resulting in a prominent fluorescence off-on
response toward hydrazine under physiological conditions. The probe is highly
selective toward hydrazine over cations, anions and other
biologically/environmentally abundant analytes. The detection limit of the probe
is 3.2ppb. The sensing mechanism was supported by 1H NMR, IR, MS and DFT
calculation. The application of the fluorescent probe in monitoring intracellular
hydrazine in glioma cell line U251 was also demonstrated.
PMID- 28692872
TI - Changes in the content of fatty acids in CA1 and CA3 areas of the hippocampus of
Krushinsky-Molodkina rats after single and fivefold audiogenic seizures.
AB - Audiogenic seizures (AS) are generalized seizures evoked by high frequency
sounds. Since the hippocampus is involved in the generation and maintenance of
seizures, the effect of AS on the composition and content of fatty acids in the
CA1 and CA3 hippocampal areas of AS-susceptible Krushinsky-Molodkina (KM) rats on
days 1, 3, and 14 after single and fivefold seizures were examined. The total
content of all fatty acids in field SA1 was found to be lower compared with the
control at all times of observation after both a single seizure or fivefold
seizures. The total content of fatty acids in field SA3 decreased at all times of
examination after a single seizure, whereas it remained unchanged on days 3 and
14 following five AS. The content of omega-3 fatty acids in both fields at all
times of observation after a single seizure and fivefold AS did not significantly
differ from that in intact animals. The absence of significant changes in the
content of stearic and alpha-linolenic acids and a considerable decrease in the
levels of palmitic, oleic, and eicosapentaenoic acids were common to both fields
at all times after both a single seizure or fivefold AS. The changes in the
content of fatty acids in the SA3 and SA1 fields of the brain of AS-susceptible
rats indicate that fatty acids are involved in both the development of seizure
activity and neuroprotective anticonvulsive processes.
PMID- 28692873
TI - Evaluation of microencapsulation of the UFV-AREG1 bacteriophage in alginate-Ca
microcapsules using microfluidic devices.
AB - The indiscriminate use of antibiotics and the emergence of resistant
microorganisms have become a major challenge for the food industry. The purpose
of this work was to microencapsulate the bacteriophage UFV-AREG1 in a calcium
alginate matrix using microfluidic devices and to study the viability and
efficiency of retention. The microcapsules were added to gel of propylene glycol
for use as an antimicrobial in the food industry. The technique showed the number
of the phage encapsulation, yielding drops with an average 100-250MUm of
diameter, 82.1+/-2% retention efficiency and stability in the gel matrix for
21days. The gel added to the microencapsulated phage showed efficiency (not
detectable on the surface) in reducing bacterial contamination on the surface at
a similar level to antimicrobial chemicals (alcohol 70%). Therefore, it was
possible to microencapsulate bacteriophages in alginate-Ca and apply the
microcapsules in gels for use as sanitizers in the food industry.
PMID- 28692874
TI - Development of double emulsion nanoparticles for the encapsulation of bovine
serum albumin.
AB - In the present work, a double emulsion was developed for the encapsulation of
Bovine Serum Albumin (BSA) as a model protein for the future encapsulation of
viral proteins. The first emulsion polydispersity index (PDI) was studied with
increasing concentrations of poly (epsilon-caprolactone) (PCL) as stabilizer
(from 16% w/v to 5% w/v) and polyvinyl alcohol (PVA) as the surfactant in the
second emulsion at 1.5% w/v. Results suggest that at decreasing concentrations of
PCL the PDI of the emulsion also decrease, indicating that viscosity of the
emulsion is crucial in the homogeneity of the resultant size distribution of the
nanoparticles. When PVA concentration in the second emulsion was increased from
1.5% w/v to 2.5% w/v the PDI also increased. To study the relationship between
the structure of the surfactant in the second emulsion and the resultant BSA
encapsulation, emulsions were prepared with Pluronic F68 and PVA both at 1.5% w/v
and PCL in the first emulsion at 5% w/v. Results indicated that Pluronic F68 was
a better stabilizer because at the same experimental conditions encapsulation of
BSA was 1.5 higher than PVA. FTIR studies confirmed the presence of BSA in the
nanoparticles. SEM and TEM microscopies showed a size distribution of 300nm-500nm
size of nanoparticles. Circular dichroism studies demonstrated that the secondary
structure of the protein was conserved after the encapsulation into the
nanoparticles.
PMID- 28692875
TI - The role of polyaminoamide-epichlorohydrin (PAE) on antibody longevity in
bioactive paper.
AB - Paper has been used to engineer many types of bio-diagnostics. A major issue to
most paper-based bio-diagnostics is the biomolecule instability causing the short
shelf-life of the diagnostics. Commercial papers contain various polymeric
additives. Polyamidoamine-epichlorohydrin (PAE), a polyelectrolyte typically used
as wet-strength agent, is commonly used in filter papers and paper towels, which
are often used as substrate in bioactive paper. However, the effect of cellulose
or polymeric additives on antibody bioactivity is unknown. This limits paper
optimization for diagnostic applications. In this study, model papers were made
with and without PAE addition. IgM Anti-A blood typing antibody was physisorbed
and dried on paper, aged for up to 9 weeks at different relative humidity (RH)
conditions and the antibody activity was measured. The antibody bioactivity was
represented as blood typing efficiency measured by image analysis. The surface
chemical composition was measured using X-ray photoelectron spectroscopy (XPS).
Antibody bioactivity loss was promoted by elevated RH, corresponding to increased
paper water content. PAE significantly reduces the paper water content under
ambient environment. Antibody bioactivity is higher on paper made with PAE under
the high humidity conditions (57.6%-84.3% RH). However, under conditions of
humidity saturation (100%RH), PAE shows little effect on reducing paper water
content nor on protecting antibody bioactivity. These results demonstrate the
water content of paper to be associated with antibody bioactivity loss.
PMID- 28692876
TI - Differentiating constitutional thinness from anorexia nervosa in DSM 5 era.
AB - INTRODUCTION: Constitutional thinness (CT) is an underweight state characterized
by normal menstruations and no change in feeding behaviour. Thinness is the only
resemblance between Anorexia Nervosa (AN) and CT. Removal of amenorrhea from the
new DSM 5 definition of AN might result in misdiagnosis between these two
populations. The objective of this study was to compare CT, AN and Control
subjects in terms of biological, anthropometric, and psychological markers in
order to better distinguish AN from CT subjects. MATERIALS AND METHODS: Body
composition, nutritional markers, pituitary hormones, bone markers and
psychological scores were evaluated in three groups of young women: fifty-six CT,
forty restrictive-type AN and fifty-four Control subjects. For every marker, a
receiver Operator Characteristics (ROC) curve was calculated to evaluate the
accuracy of differentiation between AN and CT groups. RESULTS: For most studied
parameters, CT subjects were similar to Controls but dramatically different from
AN subjects. DEBQ Restrained Eating subscale score was identified by ROC data
analysis as the only psychological parameter tested to successfully differentiate
AN from CT. Free-T3 and Leptin were shown to be powerful markers to differentiate
AN and CT populations as they were highly specific and sensitive ones.
CONCLUSION: The exclusive use of psychological testing criteria is not always
sufficient to differentiate AN and CT patients. Minimally, additional testing of
Free T3 levels, which is cheap and widely accessible for general practitioners,
should be completed to avoid misdiagnosis which could result in the
implementation of ineffective treatment plans and social stigmatization for CT
women.
PMID- 28692877
TI - Association between cerebrospinal fluid and plasma neurodegeneration biomarkers
with brain atrophy in Alzheimer's disease.
AB - The aggregation and deposition of amyloid-beta (Abeta) peptides into plaques is
an early event in Alzheimer's disease (AD), which is followed by different
aspects of neurodegeneration that can be measured in the cerebrospinal fluid
(CSF) or plasma using neurofilament light (NFL), neurogranin (Ng), total Tau (T
Tau), and phosphorylated tau (P-Tau) levels. The relationship between these
biomarkers and regional brain atrophy across the different stages of AD remains
largely unexplored. In this study, we assessed whether NFL, Ng, T-Tau, and P-Tau
levels in CSF and NFL in plasma are associated with cortical thinning and
subcortical volume loss in cognitively normal, mild cognitive impairment, and AD
subjects with and without Abeta pathology. Our main findings showed that CSF NFL
levels were associated with brain atrophy in all groups, but plasma NFL only
correlated with atrophy in symptomatic cases. In contrast, Ng was associated with
regional brain atrophy only in individuals with Abeta pathology. Altogether, our
main findings suggest that Ng is strongly associated with Abeta pathology,
whereas NFL is more unspecific.
PMID- 28692878
TI - Sex-specific association of sex hormones and gonadotropins, with brain amyloid
and hippocampal neurodegeneration.
AB - This study aimed to examine the sex-specific association between serum sex
hormones and gonadotropins and the cerebral beta-amyloid (Abeta) burden and
hippocampal neurodegeneration in subjects with normal cognition and impaired
cognition. Two hundred sixty-five older subjects received clinical assessments,
serum measurements of sex hormones, gonadotropins, 11C-Pittsburgh compound B
positron emission tomography, and magnetic resonance imaging. In females, higher
free testosterone and gonadotropin levels were associated with lower cerebral
Abeta positivity. In males, free testosterone was positively related to
hippocampal volume with significant interaction with cognitive status. Further
subgroup analyses showed that the association was significant only in impaired
cognition but not in normal cognition. Free estradiol was not associated with
Abeta burden or hippocampal neurodegeneration in either sex. These results
suggest that testosterone might inhibit the early pathological accumulation of
Abeta in females and delay neurodegeneration in males.
PMID- 28692879
TI - Anti-inflammatory effects of pitavastatin in interleukin-1beta-induced SW982
human synovial cells.
AB - The present study shows the basis for the anti-inflammatory effects of
pitavastatin in interleukin (IL)-1beta-induced human synovial cells. The SW982
cells were pretreated with pitavastatin at different concentrations (5MUM and
10MUM), followed by IL-1beta (10ng/mL) stimulation. The results showed that
pitavastatin inhibited the expression of inflammatory mediators IL-6 and IL-8.
Furthermore, pitavastatin inhibited the phosphorylation of p38, extracellular
signal-related kinase (ERK), c-jun N-terminal kinase (JNK) and protein kinase B
(Akt). It also suppressed the degradation of I kappa B alpha and blocked p65
translocation into the nucleus. These findings suggest that the mechanism
underlying the inhibitory effects of pitavastatin on IL-1beta-induced IL-6 and IL
8 release might be mediated by the suppression of mitogen-activated protein
kinase (MAPK), Akt, and nuclear factor-kappaB (NF-kappaB) signaling pathways.
These results may also indicate that pitavastatin may be potentially utilized as
an effective therapeutic agent for the treatment of osteoarthritis.
PMID- 28692880
TI - Effects of life review on mental health and well-being among cancer patients: A
systematic review.
AB - BACKGROUND: Cancer patients often experience psychological distress. Life review
has increasingly been used to enhance their mental health and well-being.
However, no systematic review has synthesized the evidence, and its effects
remain unclear. OBJECTIVE: To examine and synthesize the best available evidence
on the effects of life review on mental health and well-being among cancer
patients. DESIGN: Systematic review of randomized controlled trials and clinical
controlled trials. DATA SOURCES: Twelve electronic databases were searched for
published studies reported in English or Chinese, from inception to September
2016. Other supplementary sources, such as related websites, professional books,
reference lists, and author contacts were also used for published or unpublished
studies. REVIEW METHODS: A comprehensive literature search was conducted to
identify eligible randomized controlled trials or clinical controlled trials
about the effects of life review on cancer patients. Study selection, quality
assessment, and data extraction were independently performed by two reviewers.
The results were synthesized without meta-analysis in this review. RESULTS:
Fifteen studies (899 participants) were identified; of that total, nine studies
were rated as strong in quality, while six studies were of moderate quality. In
addition to structured life review interviews, other elements such as memory
prompts and a legacy product were integrated into life review programs. A
majority of studies indicated that life review programs benefited cancer patients
by reducing depression and anxiety, as well as improving their sense of hope,
self-esteem and quality of life. CONCLUSIONS: Life review can improve mental
health and well-being among cancer patients. This suggests that life review can
be integrated into typical cancer treatment to enhance patients' mental health
and well-being. More research with rigorous design is necessary to further
explore the effects of life review.
PMID- 28692881
TI - Detection of KRAS Exon 2 Mutations in Circulating Tumor Cells Isolated by the
ISET System from Patients with RAS Wild Type Metastatic Colorectal Cancer.
AB - INTRODUCTION: The presence of KRAS mutations in patients with metastatic
colorectal cancer (mCRC) predicts poor response to agents targeting the EGFR.
Even in patients with RAS wild type (WT) tumors, resistance eventually develops
due to multiple mechanisms, including the expansion of previously undetected KRAS
mutated clones. In this feasibility study, we aimed to detect KRAS exon 2
mutations in serial samples of circulating tumor cells (CTCs) of RAS WT patients
with mCRC captured by the Isolation by Size of Epithelial Tumor cells (ISET)
system. METHODS: CTC isolation using the ISET system was performed from
prospectively collected blood samples obtained from patients with RAS and BRAF WT
mCRC prior to first-line therapy initiation, at first imaging assessment and on
disease progression. CTCs were enumerated using hematoxylin & eosin and CD45
double stain on a single membrane spot. DNA was extracted from 5 spots and KRAS
exon 2 mutations were detected using a custom quantitative Polymerase Chain
Reaction (qPCR) assay. RESULTS: Fifteen patients were enrolled and 28 blood
samples were analyzed. In 9 (60%) patients, at least one sample was positive for
the presence of a KRAS exon 2 mutation. In 11 out of 28 samples (39.2%) with
detectable CTCs a KRAS mutation was detected; the corresponding percentages for
baseline and on progression samples were 27% and 37.5%, respectively. The most
commonly detected mutations were G13D and G12C (n=3). The presence of KRAS
mutated CTCs at baseline was not prognostic for either PFS (P=.950) or OS
(P=.383). CTC kinetics did not follow tumor response patterns. CONCLUSION: The
results demonstrate that using a qPCR-based assay, KRAS exon 2 mutations could be
detected in CTCs captured by the ISET system from patients with RAS WT primary
tumors. However, the clinical relevance of these CTCs remains to be determined in
future studies.
PMID- 28692882
TI - Capture of perchlorate by a surface-modified bio-sorbent and its bio-regeneration
properties: Adsorption, computations and biofouling.
AB - A magnetic amine-crosslinked reed (MACR) was synthesized by an insitu
precipitation method and used for perchlorate uptake. The morphological
properties of clean MACR, perchlorate-saturated MACR and bio-regenerated MACR
samples were determined using scanning electron microscopy (SEM), transmission
electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS) and zeta
potential measurements. The adsorption capacities of perchlorate by clean and bio
regenerated MACRs were determined. The density functional theory (DFT) method was
employed to evaluate the binding free energies between various anions and
ammonium/hydroxy groups. The maximum adsorption (Qmax) of perchlorate by MACR was
calculated to be 195.5-232.8 mg/g at 30-50 degrees C. The theoretical
computation of adsorption-free energies indicated that ammonium groups were
dominant in the process of perchlorate adsorption; other anions, such as [H2PO4]
, [NO3]- and [SO4]2-, showed relatively higher binding free energies than [ClO4]
, which corresponded to the results of competitive adsorption. The spent MACR was
then bio-regenerated in a sealed 250-ml conical flask with perchlorate-reducing
bacteria (30 degrees C, 160 rpm) and reached 81.4% of recovery within 3 days.
Some hydrophobic macromolecules of extracellular polymeric substances (EPS) might
have attached to the surface of MACR, which was validated by the zeta potential,
SEM and excitation emission matrix (EEM) fluorescence spectroscopy results.
PMID- 28692883
TI - Effects of multi-walled carbon nanotubes with various diameters on bacterial
cellular membranes: Cytotoxicity and adaptive mechanisms.
AB - The effect of multi-walled carbon nanotubes (MWNTs) with different diameters on
the destruction degree toward cellular membranes of bacterial has been explored
by investigating the viability of bacteria and the change of composition and
surface properties in cellular membranes with the exposure of MWNTs. The atrazine
degrading bacteria Acinetobacter lwoffii DNS32 (DNS32) is chosen as the model
species and Escherichia coli (E. coli) and Bacillus subtilis (B. subtilis) are
selected as the comparison specie. Bacterial viability testing shows that MWNTs
with smaller diameters generally display stronger toxicity to bacteria and also
influenced by many factors including the electrostatic repulsion between MWNTs
and bacteria and bacteria types. Interestingly, bacteria can self-regulate as an
adaptive response to the toxicity of MWNTs, notably, DNS32 strain presents the
adaptive responses when cultivated with MWNT60-100 through modification of fatty
acids in cell membranes, but does not exhibit similar responses when exposed to
MWNT10-20. This result may be related to the interference from MWNT10-20, which
exceeds the cellular ability to self-repair. Transmission electron microscopy
(TEM) images and flow cytometric analysis of bacteria exposed to MWNTs reveal
that the destruction of cell membrane in the DNS32 strain is more serious than
that in the B. subtilis, indicating that electrostatic repulsion between the
material and bacteria leading to the decrease of direct contact may be the
primary factor that reduces the impacts from MWNTs.
PMID- 28692884
TI - Effects of hydrated lime on radionuclides stabilization of Hanford tank residual
waste.
AB - Chemical stabilization of tank residual waste is part of a Hanford Site tank
closure strategy to reduce overall risk levels to human health and the
environment. In this study, a set of column leaching experiments using tank C-104
residual waste were conducted to evaluate the leachability of uranium (U) and
technetium (Tc) where grout and hydrated lime were applied as chemical
stabilizing agents. The experiments were designed to simulate future scenarios
where meteoric water infiltrates through the vadose zones into the interior of
the tank filled with layers of grout or hydrated lime, and then contacts the
residual waste. Effluent concentrations of U and Tc were monitored and compared
among three different packing columns (waste only, waste + grout, and waste +
grout + hydrated lime). Geochemical modeling of the effluent compositions was
conducted to determine saturation indices of uranium solid phases that could
control the solubility of uranium. The results indicate that addition of hydrated
lime strongly stabilized the uranium through transforming uranium to a highly
insoluble calcium uranate (CaUO4) or similar phase, whereas no significant
stabilization effect of grout or hydrated lime was observed on Tc leachability.
The result implies that hydrated lime could be a great candidate for stabilizing
Hanford tank residual wastes where uranium is one of the main concerns.
PMID- 28692885
TI - Ecotoxicity of water-soluble lectin from Moringa oleifera seeds to zebrafish
(Danio rerio) embryos and larvae.
AB - The evaluation of ecotoxicity of mosquito larvicidal agents (such as the water
soluble lectin from Moringa oleifera seeds, WSMoL) is an essential step to
establish the guidelines for their use. In this sense, this work evaluated the
toxicity of WSMoL to Danio rerio embryos and larvae. Embryos were exposed to
waterborne WSMoL (0.0125-0.2 mg mL-1) for 96 h and lethal and sub-lethal effects
were observed every 24 h. In the bioassays with larvae, the individuals were
exposed to the WSMoL (0.025-0.2 mg mL-1), mortality was recorded daily, and
larval swimming velocities were analyzed after 72 h and 168 h of exposure.
Additionally, acetylcholinesterase (AChE) activity of larvae was determined after
168 h of exposure. WSMoL LC50 values to embryos were 0.190, 0.133 and 0.049 mg mL
1 after 48, 72 and 96 h, respectively. No toxic endpoint was observed after
exposure for 24 h. In addition, hatching was delayed and larval length at 96 h
was reduced compared to the control. WSMoL LC50 to larvae were 0.21 and 0.135 mg
mL-1, after 24 h and 96 h, respectively. Larvae exposed to 0.1 and 0.2 mg mL-1
showed a decrease in swimming speed and a significant reduction in AChE activity.
In conclusion, WSMoL at waterborne concentrations needed for its use as a
larvicide to A. aegypti causes lethal and sublethal effects to zebrafish embryos
and larvae. Therefore, its use in waterbodies where there are non-target
organisms is not recommended.
PMID- 28692886
TI - Synthesis and characterization of oxidovanadium complexes as enzyme inhibitors
targeting dipeptidyl peptidase IV.
AB - Two oxidovanadium(IV) complexes carrying Schiff base ligands obtained from the
condensation of 4,5-dichlorobenzene-1,2-diamine and salicylaldehyde derivatives
were synthesised and characterised, including their X-ray crystallographic
structures. They were evaluated as dipeptidyl peptidase IV (DPP-IV) inhibitors
for the treatment of type 2 diabetes. These compounds were moderate inhibitors of
DPP-IV, with IC50 values of ca. 40MUM. In vivo tests showed that complexes 1 and
2 could lower significantly the level of glucose in the blood of alloxan-diabetic
mice at doses of 22.5mgV.kg-1 and 29.6mgV.kg-1, respectively. Moreover, molecular
modeling studies suggested that the oxidovanadium complexes 1 and 2 could fit
well into the active-site cleft of the kinase domain of DPP-IV. To the best of
our knowledge, this is the first report of vanadium complexes capable of
inhibiting DPP-IV.
PMID- 28692887
TI - Electron magnetic resonance data on high-spin Mn(III; S=2) ions in porphyrinic
and salen complexes modeled by microscopic spin Hamiltonian approach.
AB - The spin Hamiltonian (SH) parameters experimentally determined by EMR (EPR) may
be corroborated or otherwise using various theoretical modeling approaches. To
this end semiempirical modeling is carried out for high-spin (S=2) manganese
(III) 3d4 ions in complex of tetraphenylporphyrinato manganese (III) chloride
(MnTPPCl). This modeling utilizes the microscopic spin Hamiltonians (MSH)
approach developed for the 3d4 and 3d6 ions with spin S=2 at orthorhombic and
tetragonal symmetry sites in crystals, which exhibit an orbital singlet ground
state. Calculations of the zero-field splitting (ZFS) parameters and the Zeeman
electronic (Ze) factors (g||=gz, g?=gx=gy) are carried out for wide ranges of
values of the microscopic parameters using the MSH/VBA package. This enables to
examine the dependence of the theoretically determined ZFS parameters bkq (in the
Stevens notation) and the Zeeman factors gi on the spin-orbit (lambda), spin-spin
(rho) coupling constant, and the ligand-field energy levels (Deltai) within the
5D multiplet. The results are presented in suitable tables and graphs. The values
of lambda, rho, and Deltai best describing Mn(III) ions in MnTPPCl are determined
by matching the theoretical second-rank ZFSP b20(D) parameter and the
experimental one. The fourth-rank ZFS parameters (b40, b44) and the rho (spin
spin)-related contributions, which have been omitted in previous studies, are
considered for the first time here and are found important. Semiempirical
modeling results are compared with those obtained recently by the density
functional theory (DFT) and/or ab initio methods.
PMID- 28692888
TI - Underlying mechanisms of retained placenta: Evidence from a population based
cohort study.
AB - OBJECTIVE: To determine risk factors for retained placenta, and to identify
supporting epidemiologic evidence for the three previously-proposed mechanisms:
(i) invasive placentation, (ii) placental hypo-perfusion, and (iii) inadequate
uterine contractility. DESIGN: A retrospective population-based cohort study.
SETTING AND POPULATION: Israeli population in the southern district. METHODS:
Data were analyzed from a tertiary hospital database, between 1989 and 2014,
using univariate tests and generalized estimating equation (GEE) multivariable
models. MAIN OUTCOME MEASURES: Prevalence of retained placenta. RESULTS: The
study population included 205,522 vaginal deliveries of which 4.8% (n=9870) were
complicated with retained placenta. Previous intra-uterine procedures and
placenta-related pregnancy complications were found to be significant risk
factors for retained placenta (history of cesarean section aOR=8.82, 95%CI 8.35
9.31; history of curettage aOR=12.80, 95%CI 10.57-15.50; pre-eclampsia aOR=1.25,
95%CI 1.14-1.38; delivery of a small for gestational age neonate aOR=1.08, 95%CI
1.01-1.16; stillbirth aOR=2.34, 95%CI 1.98-2.77). During labour, the risk for
retained placenta was increased in presence of arrest of dilatation (aOR=2.03,
95%CI 1.08-3.82) or arrest of descent (aOR=1.55, 95%CI 1.22-1.96). Infections of
the uterine cavity during labour were also found to be strongly associated with
increased risk of retained placenta (endometritis aOR=2.21, 95%CI 1.64-2.97;
chorioamnionitis aOR=3.35, 95% CI 2.78-4.04). CONCLUSIONS: Supporting
epidemiologic evidence were found for all three underlying mechanisms. In
addition, there is evidence to suggest that intrauterine infection and
inflammation may also be a possible pathology associated with retained placenta.
TWEETABLE ABSTRACT: Risk factors for retained placenta support previously
proposed mechanisms in a large cohort study.
PMID- 28692889
TI - Dynamic real-time in vivo confocal laser endomicroscopy of the fallopian tube
during laparoscopy in the prevention of ovarian cancer.
AB - OBJECTIVES: Recently it has been postulated that most ovarian cancers have a
tubal origin. The identification of preinvasive tubal lesions would be of great
interest in the early diagnosis of ovarian cancer. Optical biopsy has been
developed and validated in the detection of precancerous lesions (such as
Barrett's oesophagus). The first objective of this study was to assess the
feasibility of optical biopsy in the study of fallopian tubes during laparoscopy.
The second objective was to describe the images in benign premalignant and
malignant tubes with a histopathological and immunohistochemical (p53 and Ki67
expressions) correlation. STUDY DESIGN: In this prospective study, 40 patients
undergoing laparoscopic salpingectomy for benign conditions (benign
hysterectomy), prophylactic conditions (BRCA mutation) or in case of pelvic
cancers were included after obtaining informed and signed consent prior to
surgery. The optical biopsy was performed on the fimbria of each tube in and ex
vivo. A correlation was made with the histopathological and immunohistochemical
analysis. RESULTS: The feasibility of optical biopsy was always confirmed during
laparoscopy. The optical biopsy iconography revealed different images in benign
tubal epithelium (well-defined black and grey structure), in adenomatoid tumour
(tortuous architectural organization), in STIC precancerous lesion (enlarged,
irregular and pleomorphic cells, dilated and distorted vessels) and in tubal
metastasis of high grade serous ovarian cancer (dark neoplastic cells irregular
in size and shape) CONCLUSIONS: Optical biopsy may be the first emerging mini
invasive technology that could detect tubal lesions and may be considered as a
promising tool in the early detection of ovarian cancer.
PMID- 28692890
TI - Porcine blood used as ingredient in meat productions may serve as a vehicle for
hepatitis E virus transmission.
AB - The aim of the present study was to investigate whether the use of porcine
blood(products) in food could be a risk for a hepatitis E virus (HEV) infection.
HEV RNA was detected in 33/36 batches of (non-heated) liquid products and in 7/24
spray dried powder products. Contamination levels varied among the products, but
were highest in liquid whole blood, plasma and fibrinogen reaching levels of
2.2*102 to 2.8*102 HEV genome copies per 0.2g. Sequence analyses revealed
genotype 3 strains, of which two were 100% (493nt) identical to recently
diagnosed HEV cases, although no direct epidemiological link was established. The
industry provided information on processing of blood products in (ready-to-eat)
meat. From this, it was concluded that blood products as an ingredient of
processed meat may not be sufficiently heated prior to consumption, and therefore
could be a vehicle for transmission.
PMID- 28692891
TI - Degradation studies of quizalofop-p and related compounds in soils using liquid
chromatography coupled to low and high resolution mass analyzers.
AB - A comprehensive degradation study of quizalofop-p, quizalofop-p-ethyl, quizalofop
p-tefuryl and propaquizafop in soil samples have been firstly performed using
ultra high performance liquid chromatography coupled to Orbitrap mass
spectrometry (UHPLC-Orbitrap-MS). Thus, metabolites or degradation products, such
as CHHQ (dihydroxychloroquinoxalin), CHQ (6-chloroquinoxalin-2-ol), PPA ((R)-2-(4
hydroxyphenoxy)propionic acid) and 2,3-dihydroxyquinoxaline were also monitored.
An extraction procedure based on QuEChERS procedure was used. Acidified water
(0.1M hydrochloric acid) and acidified acetonitrile (1% acetic acid, (v/v)) were
used as extraction solvents, and magnesium sulfate and sodium chloride were used
as salts. Dispersive solid phase extraction with C18 as sorbent, was needed as a
clean-up step. Several commercial products (Panarex(r), Master-D(r) and Dixon(r))
were used to evaluate the degradation of the target compounds into their
metabolites. The concentration of the main active substances (quizalofop-p
tefuryl, quizalofop-p-ethyl and propaquizafop) decreased during the degradation
studies, whereas the concentration of quizalofop-p increased. Dissipation rates
of half-live of quizalofop-p were also evaluated, and it was observed that this
compound is easily degraded, obtaining values lower than 1day. Taking into
account that quizalofop-p is the R enantiomer of quizalofop, a chiral separation
was performed by liquid chromatography coupled to tandem mass spectrometry,
concluding that in samples containing quizalofop-p-tefuryl, there was a 15%
contribution from the S enantiomer and a 85% contribution from the R enantiomer.
Metabolites such as PPA, CHHQ and CHQ were detected in soil samples after 15days
of application commercial product at concentrations between the limits of
detection (LOD) and the limits of quantification (LOQ). CHQ and CHHQ were
detected at concentrations higher than the LOQ in samples after 50 and 80days of
application, with their concentration increasing during this time up to 500%.
PMID- 28692892
TI - Photochemical behavior of dissolved and colloidal organic matter in estuarine and
oceanic waters.
AB - Chromophoric dissolved organic matter (CDOM), carbohydrates, and amino acids were
analyzed to investigate the photochemistry of total dissolved (<0.22MUm) organic
matter (DOM), high-molecular-weight (HMW, 1kDa-0.22MUm) DOM and low-molecular
weight (LMW, <1kDa) DOM at stations in the Yangtze River and its coastal area,
and in the Western Pacific Ocean. Results revealed that the humic-like and
tryptophan-like CDOM fluorescent components in riverine, coastal, and oceanic
surface waters were photodegraded during irradiation. However, the photochemical
behavior of tyrosine-like component was obscured by the excessive fluorescence
intensities of humic- and tryptophan-like fluorescent components. Light
sensitivity varied depending on the source material; terrestrially derived DOM
was more susceptible to irradiation than autochthonous DOM. In contrast to the
expected photodegradation of CDOM, photo-induced synthetic reaction transformed
the LMW matters to polysaccharides (PCHO) and degradation reaction decomposed the
HMW DOM to Monosaccharides. Colloidal DOM preferentially underwent
photodegradation, whereas permeate DOM mainly photosynthesized PCHO. The total
hydrolysable amino acid (THAA) pool changed because of the additional input by
the photodegradation of DOM or THAA itself. The compositions of THAA changed
during the irradiation experiments, indicating that the different photochemical
behavior of individual amino acids were related to their different original
photoreactivities; the relatively stable amino acids (e.g., Ser and Gly)
significantly accumulated during irradiation, whereas photo-active aromatic amino
acids (e.g. Tyr and His) were prone to photodegradation. The data presented here
demonstrated that irradiation significantly influence the conversion between
dissolved and colloid organic matter. These results can promote the understanding
of irradiation effect on the carbon and nitrogen cycle in riverine, estuarine and
oceanic ecosystems.
PMID- 28692893
TI - Contamination of organic nutrient sources with potentially toxic elements,
antibiotics and pathogen microorganisms in relation to P fertilizer potential and
treatment options for the production of sustainable fertilizers: A review.
AB - Organic nutrient sources such as farmyard manure, sewage sludge, their biogas
digestates or other animal by-products can be valuable fertilizers delivering
organic matter to the soil. Currently, especially phosphorus (P) is in the focus
of research since it is an essential plant nutrient with finite resources,
estimated to last only for some more decades. Efficient utilization of organic P
sources in agriculture will help to preserve P resources and thereby has the
potential to close nutrient cycles and prevent unwanted P-losses to the
environment, one of the major causes for eutrophication of water bodies.
Unfortunately, organic P sources usually contain also various detrimental
substances, such as potentially toxic elements or organic contaminants like
pharmaceuticals as well as pathogenic microorganisms. Additionally, the
utilization of some of these substrates such as sewage sludge or animal by
products is legally limited in agriculture because of the potential risk to
contaminate sites with potentially toxic elements and organic contaminants. Thus,
to close nutrient cycles it is important to develop solutions for the responsible
use of organic nutrient sources. The aim of this review is to give an overview of
the contamination of the most important organic nutrient sources with potentially
toxic elements, antibiotics (as one important organic contaminant) and pathogenic
microorganisms. Changes in manure and sewage sludge management as well as the
increasing trend to use such substrates in biogas plants will be discussed with
respect to potential risks posed to soils and water bodies. Some examples for
abatement options by which contamination can be reduced to produce P fertilizers
with high amounts of plant available P forms are presented.
PMID- 28692894
TI - Occurrence survey and spatial distribution of perfluoroalkyl and polyfluoroalkyl
surfactants in groundwater, surface water, and sediments from tropical
environments.
AB - The occurrence and spatial distribution of 22 selected perfluoroalkyl and
polyfluoroalkyl substances (PFASs) in surface water (n=75), groundwater (n=80)
and surficial sediment (n=15) were investigated for the first time in the
tropical areas constituted by the French Overseas Territories (French Guiana,
Guadeloupe, Martinique, Mayotte and Reunion). Descriptive statistics and
correlations between PFASs were evaluated through the use of specific statistical
treatments to handle left-censored data ("non-detects"). PFASs were ubiquitous in
these samples and detection frequencies as high as 79% for perfluorooctane
sulfonate (PFOS) and 65% for perfluorooctanoate (PFOA) were reported in surface
waters. ?PFASs was in the range60%) in the upper mainstem river and
stream sites. Stream sites were positively associated with CCA axis 2, being
characterised by high turbidity and lower pH, salinity, phosphate concentration,
channel width and canopy cover. Canopy cover, channel width, substrate
embeddedness, phosphate concentration, pH, salinity and turbidity all had a
significant effect on macroinvertebrate community composition. Using CCA
variation partitioning, water quality was, however, a better predictor of benthic
macroinvertebrate composition than sediment chemical conditions. Furthermore, our
results suggest that seasonality had little effect on structuring benthic
macroinvertebrate communities in this south-eastern zone of South Africa, despite
clear changes in sediment chemistry. This likely reflects the relative lack of
major variability in water chemistry compared to sediment chemistry between
seasons and the relatively muted variability in precipitation between seasons
than the more classic Austral temperate climates.
PMID- 28692902
TI - Profiling of soil volatile organic compounds after long-term application of
inorganic, organic and organic-inorganic mixed fertilizers and their effect on
plant growth.
AB - The complexity of soil processes involved in the production, consumption and
accumulation of volatile organic compounds (VOCs) makes hard to access the
overall dynamics of VOCs in the soil. In this study, the field soil, applied with
inorganic (CF), organic (OF) and inorganic-organic mixed (CFOF) fertilizers for
ten years was evaluated for the emission of VOCs at different temperature and
moisture levels. We identified 30-50 soil emitted VOCs representing the most
common soil VOCs groups by using the solid-phase microextraction (SPME) fiber and
gas chromatography-mass spectroscopy. The highest total emission of VOCs was
found in OF treatment, but it was non-significantly different with CF treatment.
The emission of VOCs was significantly increased with the decrease in moisture
contents and increase in the temperature of the soil. Among different fertilizer
treatments, the emission of VOCs was significantly higher in OF treatment at 5%
moisture, and in CF and OF treatments at 35 degrees C. Further, the VOCs emitted
from soil treated with CFOF showed the highest increase in plant growth while CF
and OF treatments showed similar results. The VOCs were also extracted from the
soil using methanol to better understand the dynamics of VOCs. The abundance of
VOCs extracted from the soil was 44-61%, while the richness was 65-70% higher
than the VOCs emitted from the soil in different treatments. Taken together the
results of emitted and extracted VOCs from the soil, we conclude that the
fertilizers are able to discriminate among the VOC patterns of soil. In addition,
most of the VOCs are retained in the soil and the emission of VOCs from soil
depends on the type of VOCs, soil properties and environmental conditions;
however, more research is required to find out better soil VOCs analysis methods.
PMID- 28692903
TI - Specialty satisfaction, positive psychological capital, and nursing professional
values in nursing students: A cross-sectional survey.
AB - BACKGROUND: Ideally, college majors should be chosen to achieve self-realization
and correspond to self-concept. However, some students select a major based on
extrinsic factors, rather than aptitude or interests, because of a lack of
employment opportunities. If they have negative college experiences with an
unsatisfactory major, they might not engage fully in their occupation following
graduation. OBJECTIVE: This study aimed to identify factors affecting specialty
satisfaction in preclinical practice nursing-college students. DESIGN: A cross
sectional descriptive survey. SETTING: A nonprobability convenience sample of 312
nursing-college students at colleges in Deajeon City, South Korea. The survey
questionnaire was distributed to those who agreed to participate. PARTICIPANTS:
Freshmen and sophomore nursing students (n=312). METHODS: Participants were 312
students at colleges in Deajeon City. A structured questionnaire was used to
collect data, which were analyzed using SPSS/WIN. RESULTS: Positive psychological
capital and nursing professional values were positively correlated with specialty
satisfaction. Significant predictors for specialty satisfaction included hope and
optimism (as components of positive psychological capital), the roles of nursing
service and originality of nursing (as nursing professional values), and
aptitude/interests and job value (as motives for selecting a major). CONCLUSION:
The findings suggested that nursing students' specialty satisfaction was
partially linked to positive psychological capital and professional values.
Therefore, the promotion of positive factors should be useful in enhancing
specialty satisfaction in preclinical-practice nursing-college students.
PMID- 28692905
TI - Prediction of outcome of bright light treatment in patients with seasonal
affective disorder: Discarding the early response, confirming a higher atypical
balance, and uncovering a higher body mass index at baseline as predictors of
endpoint outcome.
AB - BACKGROUND: We tested the hypothesis that the early improvement in mood after the
first hour of bright light treatment compared to control dim-red light would
predict the outcome at six weeks of bright light treatment for depressed mood in
patients with Seasonal Affective Disorder (SAD). We also analyzed the value of
Body Mass Index (BMI) and atypical symptoms of depression at baseline in
predicting treatment outcome. METHODS: Seventy-eight adult participants were
enrolled. The first treatment was controlled crossover, with randomized order,
and included one hour of active bright light treatment and one hour of control
dim-red light, with one-hour washout. Depression was measured on the Structured
Interview Guide for the Hamilton Rating Scale for Depression-SAD version (SIGH
SAD). The predictive association of depression scores changes after the first
session. BMI and atypical score balance with treatment outcomes at endpoint were
assessed using multivariable linear and logistic regressions. RESULTS: No
significant prediction by changes in depression scores after the first session
was found. However, higher atypical balance scores and BMI positively predicted
treatment outcome. LIMITATIONS: Absence of a control intervention for the six
weeks of treatment (only the first session in the laboratory was controlled).
Exclusion of patients with comorbid substance abuse, suicidality and bipolar I
disorder, and patients on antidepressant medications, reducing the
generalizability of the study. CONCLUSION: Prediction of outcome by early
response to light treatment was not replicated, and the previously reported
prediction of baseline atypical balance was confirmed. BMI, a parameter routinely
calculated in primary care, was identified as a novel predictor, and calls for
replication and then exploration of possible mediating mechanisms.
PMID- 28692904
TI - Emerging roles of the histone chaperone CAF-1 in cellular plasticity.
AB - During embryonic development, cells become progressively restricted in their
differentiation potential. This is thought to be regulated by dynamic changes in
chromatin structure and associated modifications, which act together to stabilize
distinct specialized cell lineages. Remarkably, differentiated cells can be
experimentally reprogrammed to a stem cell-like state or to alternative lineages.
Thus, cellular reprogramming provides a valuable platform to study the mechanisms
that normally safeguard cell identity and uncover factors whose manipulation
facilitates cell fate transitions. Recent work has identified the chromatin
assembly factor complex CAF-1 as a potent barrier to cellular reprogramming. In
addition, CAF-1 has been implicated in the reversion of pluripotent cells to a
totipotent-like state and in various lineage conversion paradigms, suggesting
that modulation of CAF-1 levels may endow cells with a developmentally more
plastic state. Here, we review these exciting results, discuss potential
mechanisms and speculate on the possibility of exploiting chromatin assembly
pathways to manipulate cell identity.
PMID- 28692906
TI - Development of a penetration friction apparatus (PFA) to measure the frictional
performance of surgical suture.
AB - Nowadays there is a wide variety of surgical sutures available in the market.
Surgical sutures have different sizes, structures, materials and coatings,
whereas they are being used for various surgeries. The frictional performances of
surgical sutures have been found to play a vital role in their functionality. The
high friction force of surgical sutures in the suturing process may cause
inflammation and pain to the person, leading to a longer recovery time, and the
second trauma of soft or fragile tissue. Thus, the investigation into the
frictional performance of surgical suture is essential. Despite the
unquestionable fact, little is actually known on the friction performances of
surgical suture-tissue due to the lack of appropriate test equipment. This study
presents a new penetration friction apparatus (PFA) that allowed for the
evaluation of the friction performances of various surgical needles and sutures
during the suturing process, under different contact conditions. It considered
the deformation of tissue and can realize the puncture force measurements of
surgical needles as well as the friction force of surgical sutures. The developed
PFA could accurately evaluate and understand the frictional behaviour of surgical
suture-tissue in the simulating clinical conditions. The forces measured by the
PFA showed the same trend as that reported in literatures.
PMID- 28692907
TI - Mechanical properties of the abdominal wall and biomaterials utilized for hernia
repair.
AB - Abdominal wall hernias are one of the most common and long-standing surgical
applications for biomaterials engineering. Yet, despite over 50 years of standard
use of hernia repair materials, revision surgery is still required in nearly one
third of patients due to hernia recurrence. To date, hernia mesh designs have
focused on maximizing tensile strength to prevent structural failure of the
implant. However, most recurrences occur at the biomaterial-tissue interface.
There is a fundamental gap in understanding the degree to which a mechanical
mismatch between hernia repair materials and host tissue contributes to failure
at this interface. This review summarizes the current literature related to the
anatomy and mechanics of both human and animal abdominal wall tissues, as well as
the mechanical properties of many commonly-utilized hernia repair materials. The
studies reviewed here reported greater compliance of the linea alba, larger
strains for the intact abdominal wall, and greater stiffness for the rectus
sheath and umbilical fascia when the tissues were loaded in the longitudinal
direction compared to transverse. Additionally, greater stresses were observed in
the linea alba when loaded in the transverse direction compared to longitudinal.
Given these trends, a few recommendations can be made regarding orientation of
mesh. The most compliant axis of the biomaterial should be oriented in the cranio
caudal (longitudinal) direction, and the strongest axis of the biomaterial should
be oriented in the medial-lateral (transverse) direction. The human abdominal
wall is also anisotropic, with anisotropy ratios as high as 8-9 reported for the
human linea alba. Current biomaterial designs exhibit anisotropy ratios in the
range of 1-3, and it is unclear whether an ideal ratio exists for optimal match
between mesh and tissue. This is likely dependent on implantation location as the
linea alba, rectus sheath, and other tissues of the abdominal wall exhibit
different characteristics. Given the number of unknowns yet to be addressed by
studies of the human abdominal wall, it is unlikely that any single biomaterial
design currently encompasses all of the ideal features identified. More data on
the mechanical properties of the abdominal wall will be needed to establish a
full set of guidelines for ideal mesh mechanics including strength, compliance,
anisotropy, nonlinearity and hysteresis.
PMID- 28692908
TI - Surgical outcomes of laminoplasty for cervical spondylotic myelopathy in very
elderly patients (older than 80 years): Time from symptom onset to surgery and
changes in spinal cord signal intensity on MRI.
AB - OBJECTIVE: We aimed to assess the surgical outcomes of laminoplasty for cervical
spondylotic myelopathy (CSM) in very elderly patients (older than 80 years),
focusing specifically on the time from symptom onset to surgery and on the loss
in spinal cord signal intensity on magnetic resonance imaging (MRI). PATIENTS AND
METHODS: We retrospectively reviewed 100 consecutive patients (61 males and 39
females) with CSM who underwent laminoplasty between 2006 and 2014. The patients
were stratified based on the age at the time of surgery, with Group A consisting
of 26 patients aged 80 years or older and Group B consisting of 74 patients
younger than 80 years. The severity of myelopathy was assessed in terms of the
Japanese Orthopaedic Association (JOA) score. Signal intensity loss on MRI was
graded from I to III based on the size of the area with intensity changes (Grade
I, one disk; Grade II, larger than one disk) and presence of intramedullary
hypointensity on T1-weighted sagittal scans (Grade III). Surgical outcome,
morbidities, and changes in spinal cord signal intensity on MRI were analyzed.
RESULTS: The time from symptom onset to surgery was 6.2+/-5.2 and 16.5+/
18.8months in Groups A and B, respectively, with significantly shorter duration
of symptoms in Group A (p<0.001). Compared to Group B, Group A had lower mean JOA
score preoperatively (8.8+/-1.9 vs. 10.1+/-1.7) and postoperatively (12.1+/-1.7
vs. 13.5+/-1.6), as well as lower mean JOA score recovery rate (40.7+/-12.5% vs.
51.0+/-15.4%) (p<0.05 for all). However, there was no difference between the
groups regarding achieved JOA score (Group A, 3.3+/-1.0; Group B, 3.4+/-1.0).
Preoperatively, intramedullary signal intensity change was observed in 84.6% of
patients in Group A (22/26; 3, 13, and 6 patients with Grade I, II, and III,
respectively), and in (82.4%) of patients in Group B (61/74; 18, 38, and 5
patients with Grade I, II, and , respectively), with significantly higher
incidence of Grade III pattern in Group A than in Group B. CONCLUSION: Compared
to younger patients, very elderly patients had a shorter time from symptom onset
to surgery but lower preoperative JOA score, indicating that the condition of
very elderly patients is likely to deteriorate and become severe rapidly after
the onset of myelopathy. However, it is very important to know these pathologies
and optimize the timing of surgery, as laminoplasty for CSM can be beneficial
even in very elderly patients.
PMID- 28692909
TI - Pipeline embolization of posterior communicating artery aneurysms associated with
a fetal origin posterior cerebral artery.
AB - BACKGROUND AND PURPOSE: Flow diversion may have advantages in the treatment of
posterior communicating artery (PComA) aneurysms associated with a fetal origin
posterior cerebral artery (PCA), which can be challenging to treat with
conventional techniques. However, a PComA incorporated into the aneurysm may
prevent or delay aneurysm occlusion. Also, coverage of a fetal origin PCA risks
infarction of a large vascular territory. The purpose of this study was to
examine the safety and effectiveness of using the Pipeline Embolization Device
(PED) to treat PComA aneurysms associated with a fetal origin PCA. PATIENTS AND
METHODS: Retrospective review of PComA aneurysms associated with a fetal origin
PCA treated with the PED at two neurovascular centers was performed.
Periprocedural complications and clinical and angiographic outcomes were
reviewed. RESULTS: Seven female patients underwent a total of seven PED
procedures to treat seven PcomA aneurysms associated with a fetal origin PCA. The
symptomatic complication rate was 14% (1/7) per patient and 13% (1/8) per
procedure. Angiographic follow up was obtained for 6 of 7 aneurysms. Follow-up
DSA at 5-7 months after treatment demonstrated complete occlusion of 17% (1/6) of
aneurysms. One aneurysm was retreated with a second PED and occlusion was
demonstrated 36 months after the second treatment, yielding an overall complete
occlusion rate of 33% (2/6). CONCLUSIONS: PED treatment was largely ineffective
at treating PComA aneurysms associated with a fetal origin PCA, and should only
be considered when conventional treatment options, including microsurgical
clipping, are not feasible.
PMID- 28692910
TI - Beyond symptom monitoring: Consumer needs for bipolar disorder self-management
using smartphones.
AB - OBJECTIVES: To investigate the potential use of smartphone apps to support self
management in young adults with bipolar disorder. METHODS: We recruited 89 young
adults (18-30 years) with bipolar disorder to complete a cross-sectional online
survey. The survey contained quantitative and qualitative questions regarding
technology use, current use of disorder-management apps, types of apps desired
for disorder management, and app features that users would consider important
when selecting apps. Results were analysed using descriptive statistics and
thematic analysis. RESULTS: Almost all participants used a smartphone daily and
40% currently used apps for disorder management. Of those not currently using
apps, 79% indicated they would like to try them. On average, participants rated
61% of the self-management strategies listed as desirable for app support, with
sleep-management, understanding early warning signs and triggers, and stay-well
plans the most frequently endorsed. App features considered important during app
selection were ease-of-use, scientific quality, flexibility/customisation, and
data privacy. CONCLUSIONS: The results indicate that young adults with bipolar
disorder are interested in a wide range of apps for self-management. Participants
were interested in apps to support self-management strategies considered
clinically important for disorder management. Many of these app needs are
currently unmet. Results suggest diversifying and prioritising app capabilities
to ensure evidence-based resources for a broader range of app functions are
available to consumers.
PMID- 28692911
TI - Relationship between heavy metal accumulation and morphometric parameters in
European hare (Lepus europaeus) inhabiting various types of landscapes in
southern Poland.
AB - To evaluate the influence of hazardous substances in the environment, studies of
pollutant accumulation in wild living animals are needed. Studies dealing with
heavy metal contamination in mammals usually focus on a single organ. We
investigated accumulation of heavy metals as well as iron in European hare (Lepus
europaeus) living in southern Poland, Malopolska Province. Hares were captured
during the hunting season. We tested metal accumulation in 14 organs and tissues
using 35 individuals with known body weight and sex inhabiting agricultural,
industrial and other types of landscapes. To obtain deeper insight into
contamination patterns, we used accumulation data from the liver since it is the
most frequently investigated organ and prone to pollution accumulation. Based on
the data obtained for the liver, we tested the impact of metal pollution on hare
morphology, including body length and several skull cranimetric parameters.
Metals content differed between organs. Moreover, individuals from industrial
areas had higher Cd content in their body. We distinguished two groups of
elements: the first group, Cd, Fe and Zn, revealed the highest toxic effect in
the liver and kidneys; the second group, Cr, Ni, and Pb, accumulated primarily in
the brain. Hares inhabiting industrial areas had higher concentration of Cd and
Pb, and lower levels of Cr and Fe in their liver in comparison with those from
agricultural and forest habitats. Heavy metals had an effect on body length that
was negatively associated with Cr levels. Skull diastema length was associated
positively with accumulation of Cd and Pb. We showed that hare organs and tissues
could be used as bioindicators of environmental pollution by heavy metals.
PMID- 28692912
TI - Effects of molybdenum and cadmium on the oxidative damage and kidney apoptosis in
Duck.
AB - Molybdenum (Mo) is an essential element for human beings and animals; however,
high dietary intake of Mo can lead to adverse reactions. Cadmium (Cd) is one of
the major transitional metals which has toxic effects in animals. To investigate
the co-induced toxic effects of Mo and Cd on oxidative damage and kidney
apoptosis in duck, 120 ducks were randomly divided into control group and 5
treatment groups which were treated with a commercial diet containing different
dosages of Mo and Cd. Kidney samples were collected on the 60th and 120th days to
determine the mRNA expression levels of ceruloplasmin (CP), metallothionein (MT),
Bak-1, and Caspase-3 by quantitative RT-PCR. Additionally, we also determined the
antioxidant activity indexes and contents of Mo, Cd, copper (Cu), iron (Fe), zinc
(Zn), and selenium (Se) in serum. Meanwhile, ultrastructural changes of the
kidney were observed. The results showed that glutathione reductase (GR) activity
and CP level in serum were decreased in combination groups. In addition, the
antioxidant indexes were decreased in co-treated groups compared with single
treated groups. The mRNA expression levels of Bak-1 and Caspase-3 increased in co
treated groups. The mRNA expression level of CP in high-dose combination group
was downregulated, while the mRNA expression of MT was upregulated except for low
dose Mo group. Additionally, in the later period the content of Cu in serum
decreased in joint groups while the contents of Mo and Cd increased. In addition,
ultrastructural changes showed mitochondrial crest fracture, swelling, deformed
nuclei, and karyopyknosis in co-treated groups. Taken together, it was suggested
that dietary Mo and Cd might lead to oxidative stress, kidney apoptosis and
disturb homeostasis of trace elements in duck, and it showed a possible
synergistic relationship between the two elements.
PMID- 28692913
TI - Particle and bioaerosol characteristics in a paediatric intensive care unit.
AB - The paediatric intensive care unit (PICU) provides care to critically ill
neonates, infants and children. These patients are vulnerable and susceptible to
the environment surrounding them, yet there is little information available on
indoor air quality and factors affecting it within a PICU. To address this gap in
knowledge we conducted continuous indoor and outdoor airborne particle
concentration measurements over a two-week period at the Royal Children's
Hospital PICU in Brisbane, Australia, and we also collected 82 bioaerosol samples
to test for the presence of bacterial and viral pathogens. Our results showed
that both 24-hour average indoor particle mass (PM10) (0.6-2.2MUgm-3, median:
0.9MUgm-3) and submicrometer particle number (PN) (0.1-2.8*103pcm-3, median:
0.67*103pcm-3) concentrations were significantly lower (p<0.01) than the outdoor
concentrations (6.7-10.2MUgm-3, median: 8.0MUgm-3 for PM10 and 12.1-22.2*103pcm
3, median: 16.4*103pcm-3 for PN). In general, we found that indoor particle
concentrations in the PICU were mainly affected by indoor particle sources, with
outdoor particles providing a negligible background. We identified strong indoor
particle sources in the PICU, which occasionally increased indoor PN and PM10
concentrations from 0.1*103 to 100*103pcm-3, and from 2MUgm-3 to 70MUgm-3,
respectively. The most substantial indoor particle sources were nebulization
therapy, tracheal suction and cleaning activities. The average PM10 and PN
emission rates of nebulization therapy ranged from 1.29 to 7.41mgmin-1 and from
1.20 to 3.96pmin-1*1011, respectively. Based on multipoint measurement data, it
was found that particles generated at each location could be quickly transported
to other locations, even when originating from isolated single-bed rooms. The
most commonly isolated bacterial genera from both primary and broth cultures were
skin commensals while viruses were rarely identified. Based on the findings from
the study, we developed a set of practical recommendations for PICU design, as
well as for medical and cleaning staff to mitigate aerosol generation and
transmission to minimize infection risk to PICU patients.
PMID- 28692914
TI - Antibiofilm potential of 16-oxo-cleroda-3, 13(14) E-diene-15 oic acid and its
five new gamma-amino gamma-lactone derivatives against methicillin resistant
Staphylococcus aureus and Streptococcus mutans.
AB - The clerodane diterpenoids 16-oxo-cleroda-3, 13(14) E-diene-15 oic acid (1) and
kolavenic acid (2) isolated from Polyalthia longifolia var. pendula (Linn.) were
previously reported for their antimicrobial activity. Thus present study was
designed to investigate the biofilm inhibiting potential of these diterpenoids (1
2) and five new lactone derivatives (3-7) of 1 against methicillin resistant
Staphylococcus aureus (MRSA), Streptococcus mutans, Klebsiella pneumoniae and
Proteus mirabilis. Compounds 1 and 3 at 10-20 MUg/mL were found to be
bacteriostatic and significantly reduced the biofilm formation and metabolically
active cells of MRSA and S. mutans up to 90%. Parental diterpenoid (1) at 10 and
16 MUg/mL significantly eradicated the preformed biofilm of both pathogens. Both
the compounds also delayed acid production at minimum inhibitory (MIC) and sub
inhibitory concentrations (sub MIC). Florescence and scanning electron microscopy
further confirms the biofilm inhibiting potential of compounds 1 and 3 and
displayed disrupted biofilms at MIC and sub MIC levels. The gene expression of
MRSA and S. mutans responsible for biofilm formation was also altered. Moreover,
the observed anti-virulence properties and delayed bacterial growth after 10 min
of exposure to the test compounds 1 and 3 make them a promising class of
antibiofilm agents.
PMID- 28692915
TI - Triazole derivatives and their anti-tubercular activity.
AB - Tuberculosis (TB) remains one of the most widespread and leading deadliest
diseases, threats one-third of the world's population. Although numerous efforts
have been undertaken to develop new anti-TB agents, only a handful of compounds
have entered human trials in the past 5 decades. Triazoles including 1,2,3
triazole and 1,2,4-triazole are one of the most important classes of nitrogen
containing heterocycles that exhibited various biological activities. Triazole
derivatives are regarded as a new class of effective anti-TB candidates owing to
their potential anti-TB potency. Thus, molecules containing triazole moiety may
show promising in vitro and in vivo anti-TB activities and might be able to
prevent the drug resistant to certain extent. This review outlines the advances
in the application of triazole-containing hybrids as anti-TB agents, and
discusses the structure-activity relationship of these derivatives.
PMID- 28692916
TI - Discovery, mechanism and metabolism studies of 2,3-difluorophenyl-linker
containing PARP1 inhibitors with enhanced in vivo efficacy for cancer therapy.
AB - Poly (ADP-ribose) polymerase 1 (PARP1) is overexpressed in a variety of cancers,
especially breast and ovarian cancers, and tumor cell lines deficient in breast
cancer gene 1/2 (BRCA1/2) are highly sensitive to PARP1 inhibition. In this
study, with the help of molecular docking, we identified a novel series of 2,3
difluorophenyl-linker analogues (15-54) derived from olaparib (1) as PARP1
inhibitors. Lead optimization led to the identification of 47, which showed high
selectivity and high potency against PARP1 enzyme (IC50 = 1.3 nM), V-C8 cells
(IC50 = 0.003 nM), Capan-1 cells (IC50 = 7.1 nM) and MDA-MB-436 cells (IC50 = 0.2
nM). Compound 47 had more potent PARP1-DNA trapping and double-strand breaks
(DSBs)-induction activities than 1 and induced G2/M arrest and caspase-dependent
apoptosis. Compound 47 (50 mg/kg, 94.2%) had a more beneficial effect on tumor
growth inhibition than 1 (100 mg/kg, 65.0%) in a BRCA1-mutated xenograft model
and significantly inhibited tumor growth (40 mg/kg, 48.1%) in a BRCA2-mutated
xenograft model, with no negative influence on the body weight of the mice.
Collectively, these data demonstrated that 47 might be an excellent drug
candidate for the treatment of cancer, especially for BRCA-deficient tumors.
PMID- 28692917
TI - Tuning of beta-glucosidase and alpha-galactosidase inhibition by generation and
in situ screening of a library of pyrrolidine-triazole hybrid molecules.
AB - The preliminary screening of two libraries of epimeric (pyrrolidin-2-yl)triazoles
(14a-s and 22a-s), generated via click chemistry, allowed the rapid
identification of four alpha-galactosidase (coffee beans) inhibitors (22b,k,p,r)
and two beta-glucosidase (almond) inhibitors (14b,f) in the low MUM range. The
additional biological analysis of 14b,f towards beta-glucocerebrosidase (human
lysosomal beta-glucosidase), as target enzyme for Gaucher disease, showed a good
correlation with the inhibition results obtained for the plant (almond) enzyme.
Surprisingly, although these compounds showed inhibition towards beta
glucocerebrosidase as acid hydrolase, they did not inhibit bovine liver beta
glucosidase as neutral hydrolase. In contrast to what was observed for beta
glucosidase inhibition, the coffee bean alpha-galactosidase inhibitors of the
epimeric library (22b,k,p,r) only showed weak inhibition towards human lysosomal
alpha-galactosidase.
PMID- 28692918
TI - Valorization of waste glycerol for the production of poly (3-hydroxybutyrate) and
poly (3-hydroxybutyrate-co-3-hydroxyvalerate) copolymer by Cupriavidus necator
and extraction in a sustainable manner.
AB - Glycerol is a by-product of many industrial processes and huge amounts of it are
generated in the form of waste, thereby necessitating a search for the method of
its disposal. An interesting solution is the valorization of crude glycerol into
value added product such as polyhydroxyalkanoates (PHAs). The feasibility of
producing PHAs by Cupriavidus necator was evaluated using crude glycerol (WG).
Various cultivation strategies were designed for the production of poly(3
hydroxybutyrate-co-3-hydroxyvalerate) copolymer by adding different organic acids
as precursors at different concentrations levels. Batch cultivation of poly(3
hydroxybutyrate-co-3-hydroxyvalerate) production showed accumulation of 6.76g/L
biomass containing 4.84g/L copolymer on WG with a maximum 3-hydroxyvalerate
content of 24.6mol%. PHAs extraction using a non-toxic and recyclable solvent,
1,2 propylene carbonate, showed the highest recovery yield (90%) and purity (93%)
at 120 degrees C temperature and 30min incubation. This is the first report on
jatropha based glycerol valorization for poly(3-hydroxybutyrate-co-3
hydroxyvalerate) production coupled with extraction using non-toxic solvent.
PMID- 28692919
TI - Influence of organic load rate (OLR) on the hydrolytic acidification of 2-butenal
manufacture wastewater and analysis of bacterial community structure.
AB - The influence of organic loading rate (OLR) on the performance of hydrolytic
acidification process for treating 2-butenal manufacture wastewater was
comprehensively studied, while its impact on microbial community was thoroughly
investigated. The results demonstrated that over 21.0% of the average COD removal
rate was observed in the range of OLR from 0.52 to 3.98g COD/L.d, whereas it
reduced to 15.3% with increasing OLR to 6.09g COD/L.d. The acidification degree
dramatically decreased from 17.1% to 4.7% when OLR increased from 3.98 to 6.09g
COD/L.d. In addition, the removal rates of three kinds of typical matters were
less than 65% at the OLR 6.09g COD/L.d. Illumina MiSeq sequencing revealed that
Proteobacteria, Chloroflexi, Firmicutes, and Bacteroidetes were dominant phyla at
different OLRs. Finally, multivariate analysis suggested that the genera
Longilinea and T78 had a positive correlation with the degradation of three kinds
of typical matters and COD removal rates.
PMID- 28692920
TI - The effect of motorcycle helmet fit on estimating head impact kinematics from
residual liner crush.
AB - Proper helmet fit is important for optimizing head protection during an impact,
yet many motorcyclists wear helmets that do not properly fit their heads. The
goals of this study are i) to quantify how a mismatch in headform size and
motorcycle helmet size affects headform peak acceleration and head injury
criteria (HIC), and ii) to determine if peak acceleration, HIC, and impact speed
can be estimated from the foam liner's maximum residual crush depth or residual
crush volume. Shorty-style helmets (4 sizes of a single model) were tested on
instrumented headforms (4 sizes) during linear impacts between 2.0 and 10.5m/s to
the forehead region. Helmets were CT scanned to quantify residual crush depth and
volume. Separate linear regression models were used to quantify how the response
variables (peak acceleration (g), HIC, and impact speed (m/s)) were related to
the predictor variables (maximum crush depth (mm), crush volume (cm3), and the
difference in circumference between the helmet and headform (cm)). Overall, we
found that increasingly oversized helmets reduced peak headform acceleration and
HIC for a given impact speed for maximum residual crush depths less than 7.9mm
and residual crush volume less than 40cm3. Below these levels of residual crush,
we found that peak headform acceleration, HIC, and impact speed can be estimated
from a helmet's residual crush. Above these crush thresholds, large variations in
headform kinematics are present, possibly related to densification of the foam
liner during the impact.
PMID- 28692921
TI - Exploring the relationship between non suicidal self-injury and borderline
personality traits in young adults.
AB - Non-suicidal self-injury (NSSI) is highly prevalent during late adolescence and
young adulthood. There is some evidence of a link between NSSI and Borderline
Personality Disorder (BPD), but little is known about the association between BPD
traits and the various functions that maintain NSSI. The main purpose of this
study was to explore the association between borderline personality traits and
NSSI functions in a sample of college students. We also compared NSSI functions
in college students who engaged in NSSI to those in an age-matched sample of BPD
patients. This study included a total of 238 college students and 36 BPD
patients. Participants were asked to complete a number of clinical measures. In
the non-clinical sample, BPD features were more pronounced in the presence of
NSSI, and we observed a differential relationship between NSSI functions and
psychopathological BPD-traits. The NSSI clinical variables most strongly
associated with BPD were frequency, variety of methods and severity, but not age
of onset. Our results provide new information on the relationship between BPD and
NSSI in young adults, and could be used to improve the early detection of
vulnerable BPD-individuals and in planning NSSI treatment.
PMID- 28692922
TI - Iris structure and minor physical anomalies in schizophrenia.
AB - This study compared five human iris characteristics and minor physical anomalies
(MPAs) between patients with schizophrenia (n = 32) and controls (n = 31).
Correlations between iris characteristics and MPAs were expected, due to their
same ectodermic origin. Iris macro photos were taken and quantified in five
categories mentioned before. MPAs were also examined in both groups. Our results
show significant differences in the frequency of pigment dots of the iris and
total number of MPAs between groups. Other significant differences were found in
the extension of concentric furrows, as they were more common in healthy
subjects, while Wolfflin nodules occurred significantly more often in patients
with schizophrenia. Expected difference in Fuch's crypts could not be observed
between groups. Light eye color was positively correlated to pigment dots and
Wolfflin nodules, and negatively correlated with concentric furrows. Dark eye
color showed positive correlation with concentric furrows, and negative
correlation with pigment dots and concentric furrows. A gender effect could also
been observed: male individuals showed moderate positive correlations between
pigment dots and total MPAs frequency, while this couldn't be observed in the
female group. Our findings suggest possible connections between iris
characteristics and MPAs, where males are more prone to deviations.
PMID- 28692923
TI - Permeability recovery of fouled forward osmosis membranes by chemical cleaning
during a long-term operation of anaerobic osmotic membrane bioreactors treating
low-strength wastewater.
AB - Anaerobic osmotic membrane bioreactor (AnOMBR) has gained increasing interests in
wastewater treatment owing to its simultaneous recovery of biogas and water.
However, the forward osmosis (FO) membrane fouling was severe during a long-term
operation of AnOMBRs. Here, we aim to recover the permeability of fouled FO
membranes by chemical cleaning. Specifically speaking, an optimal chemical
cleaning procedure was searched for fouled thin film composite polyamide FO (TFC
FO) membranes in a novel microfiltration (MF) assisted AnOMBR (AnMF-OMBR). The
results indicated that citric acid, disodium ethylenediaminetetraacetate (EDTA
2Na), hydrochloric acid (HCl), sodium dodecyl sulfate (SDS) and sodium hydroxide
(NaOH) had a low cleaning efficiency of less than 15%, while hydrogen peroxide
(H2O2) could effectively remove foulants from the TFC-FO membrane surface (almost
100%) through oxidizing the functional group of the organic foulants and
disintegrating the colloids and microbe flocs into fine particles. Nevertheless,
the damage of H2O2 to the TFC-FO membrane was observed when a high cleaning
concentration and a long duration were applied. In this case, the optimal
cleaning conditions including cleaning concentration and time for fouled TFC-FO
membranes were selected through confocal laser scanning microscope (CLSM) and
scanning electron microscopy (SEM) images and the flux recovery rate. The results
suggested that the optimal cleaning procedure for fouled TFC-FO membranes was use
of 0.5% H2O2 at 25 degrees C for 6 h, and after that, the cleaned TFC-FO
membrane had the same performance as a virgin one including water flux and
rejection for organic matters and phosphorus during the operation of AnMF-OMBR.
PMID- 28692924
TI - Experimental co-infection of infectious bronchitis and low pathogenic avian
influenza H9N2 viruses in commercial broiler chickens.
AB - In this study, commercial broilers were experimentally infected with single
(classical IBV, variant IBV or AIV-H9N2) or mixed AIV-H9N2 with classical,
variant or vaccine strains of IBV. Birds were monitored for clinical and
pathological outcomes and virus shedding for 10days post infection (DPI).
Clinical signs were limited to the respiratory tract in all challenged groups and
varied from mild to moderate mouth breathing to severe respiratory signs with
snorting sound and extended head. Mortalities were only recorded in mixed AIV
H9N2/variant IBV challenge group. AIV-H9N2 challenge caused tracheal petechial
hemorrhage that progressed to tracheal congestion and caseation. In mixed AIV
H9N2/IBV vaccine challenge, severe tracheitis with bronchial cast formation was
observed. In mixed AIV-H9N2/variant IBV challenge severe congestion of the
tracheal mucosa and excessive exudates with a tendency to form tubular casts were
observed. Kidney ureate deposition was only observed in variant IBV challenge
group. Histopathologically, tracheal congestion, severe degeneration, and
deciliation were noticed in all groups of mixed infection. Interestingly,
hemorrhage and atrophy were observed in thymus gland of birds challenged with
single AIV-H9N2 or mixed AIV-H9N2/IBV. There was no difference in the tracheal
shedding level of variant IBV between single and mixed infected groups while
classical IBV shedding increased in mixed infection group. Interestingly, the AIV
H9N2 showed constantly high shedding titers till 7DPI with variant or vaccine IBV
co-infection. In conclusion, co-infection of IBV and AIV-H9N2 induced severe
clinical outcome and high mortality. Also, IBV co-infection increased the
shedding of AIV-H9N2 in experimentally infected birds.
PMID- 28692925
TI - Role of the adjunctive antimicrobial photodynamic therapy to periodontal
treatment at plasmatic oxidative stress and vascular behavior.
AB - BACKGROUND: To evaluate for the first time in vivo the effects of methylene blue
(MB) photosensitizer dissolved in ethanol in antimicrobial photodynamic therapy
(aPDT) as adjuvant periodontal treatment, at plasmatic oxidative stress and
vascular behavior in rat model. METHODS: Wistar rats were divided into negative
control (NC, no periodontitis) and positive control (PC, with periodontitis,
without any treatment). The other groups had periodontitis and were treated with
scaling and root planing (SRP); SRP+aPDT+MB dissolved in water (aPDT I);
SRP+aPDT+MB dissolved in ethanol (aPDT II). The periodontitis was induced by
ligature at the mandibular right first molar. At 7/15/30days, rats were
euthanized, the plasma was used to determine oxidative stress parameters and
gingival tissue for histomorphometric analysis. RESULTS: PC showed higher
thiobarbituric acid reactive substances levels in 7/15/30days. aPDT II was able
to block the lipid peroxidation, especially between 15th and 30th days.
Glutathione reduced levels were consumed in PC, aPDT I and II groups throughout
the experiment. aPDT II increased the vitamin C levels which were restored in
this group in the 30th day. aPDT II group showed the highest number of blood
vessels. CONCLUSION: In summary, the aPDT with MB dissolved in ethanol provides
better therapeutic responses in periodontitis treatment.
PMID- 28692926
TI - Phototoxic assessment of a sunscreen formulation and its excipients: An in vivo
and in vitro study.
AB - BACKGROUND: Cosmetic preservatives are used to protect cosmetic formulations and
improve its shelf-life. However, these substances may exert phototoxic effects
when used under sunlight. OBJECTIVE: To assess safety, efficacy and putative
phototoxic effects of a sunscreen formulation SPF 30 and its excipients.
MATERIALS/METHODS: Irradiation was performed with solar simulated light (SSL) and
the sunscreen from the School of Pharmacy/UFRJ/Brazil. We used albino hairless
mice in different groups (control (G1), only irradiated (G2), sunscreen plus
irradiation (G3) and vehicle plus irradiation (G4) for morphological assessment
and immunefluorescence detection to OKL38. In vitro analyses were with a
Saccharomyces cerevisiae (SC) strain plus SSL in the presence of methylparaben,
propylparaben, imidazolidinyl urea, aminomethyl propanol and their association.
RESULTS: G3 and G4 displayed photosensitization leading to thickening of the
epidermis and increased dermal cellularity. G4 displayed strong OKL38 labeling
when compared with other groups. Aminomethyl propanol, methylparaben and
propylparaben are endowed with phototoxic activity against SC. Propylparaben
displayed the highest phototoxic effect, followed by excipients association.
CONCLUSIONS: The sunscreen's vehicle is endowed with phototoxic activity.
Propylparaben was the most phototoxic agent, increasing the overall phototoxicity
of excipient association, pointing to a critical concern regarding vehicle
associations intended to cosmetic purposes.
PMID- 28692927
TI - Coal emissions adverse human health effects associated with ultrafine/nano
particles role and resultant engineering controls.
AB - There are multiple elements which enable coal geochemistry: (1) boiler and
pollution control system design parameters, (2) temperature of flue gas at
collection point, (3) feed coal and also other fuels like petroleum coke, tires
and biomass geochemistry and (4) fuel feed particle size distribution homogeneity
distribution, maintenance of pulverisers, etc. Even though there is a large
number of hazardous element pollutants in the coal-processing industry,
investigations on micrometer and nanometer-sized particles including their
aqueous colloids formation reactions and their behaviour entering the environment
are relatively few in numbers. X-ray diffraction (XRD), High Resolution
Transmission Electron microscopy (HR-TEM)/ (Energy Dispersive Spectroscopy) EDS/
(selected-area diffraction pattern) SAED, Field Emission-Scanning Electron
Microscopy (FE-SEM)/EDS and granulometric distribution analysis were used as an
integrated characterization techniques tool box to determine both geochemistry
and nanomineralogy for coal fly ashes (CFAs) from Brazil's largest coal power
plant. Ultrafine/nano-particles size distribution from coal combustion emissions
was estimated during the tests. In addition the iron and silicon content was
determined as 54.6% of the total 390 different particles observed by electron
bean, results aimed that these two particles represent major minerals in the
environment particles normally. These data may help in future investigations to
asses human health actions related with nano-particles.
PMID- 28692928
TI - Associations between prenatal arsenic exposure with adverse pregnancy outcome and
child mortality.
AB - BACKGROUND: Chronic arsenic exposure is a public health concern in many parts of
the world, with elevated concentrations in groundwater posing a threat to
millions of people. Arsenic is associated with various cancers and an array of
chronic diseases; however, the relationship with adverse pregnancy outcomes and
child mortality is less established. OBJECTIVES: We evaluated associations
between individual-level prenatal arsenic exposure with adverse pregnancy
outcomes and child mortality in a pregnancy study among 498 women nested in a
larger population-based cohort in rural Bangladesh. METHODS: Creatinine-adjusted
urinary total arsenic concentration, a comprehensive measure of exposure from
water, food, and air sources, reflective of the prenatal period was available for
participants. Self-reported pregnancy outcomes (livebirth, stillbirth,
spontaneous/elective abortion) were ascertained. Generalized estimating
equations, accounting for multiple pregnancies of participants, were used to
estimate odds ratios and 95% confidence intervals in relation to adverse
pregnancy outcomes. Vital status of livebirths was subsequently ascertained
through November 2015. Cox proportional hazards models were used to estimate
hazard ratios and 95% confidence intervals in relation to child mortality.
RESULTS: We observed a significant association between prenatal arsenic exposure
and the risk of stillbirth (greater than median; adjusted OR = 2.50; 95% CI =
1.04, 6.01). We also observed elevated risk of child mortality (greater than
median; adjusted HR = 1.92; 95% CI = 0.78, 4.68) in relation to prenatal arsenic
exposure. CONCLUSIONS: Prospective studies should continue to evaluate prenatal
and early life health effects of arsenic exposure and arsenic remediation
strategies for women of child-bearing age.
PMID- 28692929
TI - A new recycling technique for the waste tires reuse.
AB - In this series of laboratory experiments, the feasibility of using fixed bed
biofilm carriers (FBBC) manufactured from existing reclaimed waste tires (RWTs)
for wastewater treatment was evaluated. To assess polyamide yarn waste tires as a
media, the fixed bed sequence batch reactor (FBSBR) was evaluated under different
organic loading rate (OLRs). An experimental model was used to study the kinetics
of substrate consumption in biofilm. Removal efficiency of soluble chemical
oxygen demand (SCOD) ranged by 76-98% for the FBSBR compared to 71-96% in a
sequencing batch reactor (SBR). Removal efficiency of FBBC was significantly
increased by inoculating these RWTs carriers. The results revealed that the
sludge production yield (Yobs) was significantly less in the FBSBR compared to
the SBR (p < 0.01). It also produced less sludge and recorded a lower
stabilization ratio (VSS/TSS). The findings show that the Stover-Kincannon model
was the best fit (R2 > 99%) in a FBSBR. Results from this study suggest that RWTs
to support biological activity for a variety of wastewater treatment applications
as a biofilm carrier have high potential that better performance as COD and TSS
removal and sludge settling properties and effluent quality supported these
findings.
PMID- 28692930
TI - Evaluation of dynamic scaling of growing interfaces in EEG fluctuations of
seizures in animal model of temporal lobe epilepsy.
AB - Epileptic seizures, as a dynamic phenomenon in brain behavior, obey a scale-free
behavior, frequently analyzed by electrical activity recording. This recording
can be seen as a surface that roughens with time. Dynamic scaling studies
roughening processes or growing interfaces. In this theory, a set of exponents
obtained from scale invariance properties- characterize rough interfaces growth.
The aim of the present study was to investigate scaling behavior in EEG time
series fluctuations of a chemical animal model of temporal lobe epilepsy, with
dynamic scaling to detect changes on seizure onset. We analyzed local variables
in different sampling intervals and estimated rough, scaling and dynamic
exponents. Results exhibited long-range correlations in interictal activity.
Results of renormalization and data collapsing confirmed that each epoch of EEG
fluctuations for interictal, preictal and postictal collapse in a curve in
different scales, each segment independently; remarkably, we found non-scaling
behavior in seizures epochs. Data for the different sampling intervals for ictal
period do not collapse in one curve, which implies that ictal activity does not
exhibit the same scaling behavior than the other epochs. Statistical significant
differences of growth exponent were found between interictal and ictal segment,
while for scaling exponent, significant differences were found between interictal
and postictal segment. These results confirm the potential of scaling exponents
as characteristic parameters to detect changes on seizure onset, which suggests
their use as inputs for analysis methods for seizure detection in long-term
recordings, while changes in growth exponent are potentially useful for
prediction purposes.
PMID- 28692931
TI - Automatic discrimination of actinic keratoses from clinical photographs.
AB - BACKGROUND AND OBJECTIVE: Actinic keratoses (AK) are common premalignant skin
lesions that can progress to invasive skin squamous cell carcinoma (sSCC). The
subtle accumulation of multiple AK in aging individuals increases the risk of
sSCC development, and this underscores the need for efficient treatment and
patient follow-up. Our objectives were to develop a method based on color texture
analysis of standard clinical photographs for the discrimination of AK from
healthy skin and subsequently to test the developed approach in the
quantification of field-directed treatment interventions. METHODS: AK and healthy
skin in clinical photographs of 22 patients were demarcated by experts and
regions of interest (ROIs) of 50 * 50 pixels were cropped. The data set comprised
6010 and 13915 ROIs from AK and healthy skin, respectively. Color texture
features were extracted using local binary patterns (LBP) or texton frequency
histograms and evaluated employing a support vector machine (SVM) classifier.
Classifier evaluation was performed using a leave-one-patient-out scheme in RGB,
YIQ and CIE-Lab color spaces. The best configuration of the SVM model was tested
using 157 AK and 216 healthy skin rectangular regions of arbitrary size. AK
treatment outcome was evaluated in an additional group of eight patients with 32
skin lesions. RESULTS: The best configuration of the discrimination model was
achieved by employing LBP color texture descriptors estimated from the Y and I
components of the YIQ color space. The sensitivity and specificity of the SVM
model were 80.1% and 81.1% at ROI level and 89.8% and 91.7% at region level,
respectively. Based on the classifier results the quantitative AK reduction was
83.6%. CONCLUSIONS: It is important that patients with AK seek evaluation for
treatment to reduce the risk of disease progression. Efficient patient follow-up
and treatment evaluation require cost-effective and easy to use approaches. The
proposed SVM discrimination model based on LBP color texture analysis renders
clinical photography a practical, widely available and cost-effective tool for
the evaluation of AK burden and treatment efficacy.
PMID- 28692932
TI - Axon guidance pathways served as common targets for human speech/language
evolution and related disorders.
AB - Human and several nonhuman species share the rare ability of modifying acoustic
and/or syntactic features of sounds produced, i.e. vocal learning, which is the
important neurobiological and behavioral substrate of human speech/language. This
convergent trait was suggested to be associated with significant genomic
convergence and best manifested at the ROBO-SLIT axon guidance pathway. Here we
verified the significance of such genomic convergence and assessed its functional
relevance to human speech/language using human genetic variation data. In normal
human populations, we found the affected amino acid sites were well fixed and
accompanied with significantly more associated protein-coding SNPs in the same
genes than the rest genes. Diseased individuals with speech/language disorders
have significant more low frequency protein coding SNPs but they preferentially
occurred outside the affected genes. Such patients' SNPs were enriched in several
functional categories including two axon guidance pathways (mediated by netrin
and semaphorin) that interact with ROBO-SLITs. Four of the six patients have
homozygous missense SNPs on PRAME gene family, one youngest gene family in human
lineage, which possibly acts upon retinoic acid receptor signaling, similarly as
FOXP2, to modulate axon guidance. Taken together, we suggest the axon guidance
pathways (e.g. ROBO-SLIT, PRAME gene family) served as common targets for human
speech/language evolution and related disorders.
PMID- 28692933
TI - Contrast enhancement of nanomaterials using phase plate STEM.
AB - Visualizing materials composed of light elements is difficult, and the
development of an imaging method that enhances the phase contrast of such
materials has been of much interest. In this study, we demonstrate phase-plate
scanning transmission electron microscopy (P-STEM), which we developed recently,
and its application to nanomaterials. An amorphous carbon film with a small hole
in its center was used to control the phase of incident electron waves, and the
phase-contrast transfer function (PCTF) was modified from sine-type to cosine
type. The modification of the PCTF enhances image contrast with a spatial
frequency below 1 nm-1. The PCTF for P-STEM with a spatial frequency below 1 nm-1
is about three times stronger than that of bright field STEM. The ratio obtained
using power spectra is consistent with the result obtained from images of quantum
dots. The image contrast of biological materials was also enhanced by P-STEM.
PMID- 28692934
TI - Measuring nanometre-scale electric fields in scanning transmission electron
microscopy using segmented detectors.
AB - Electric field mapping using segmented detectors in the scanning transmission
electron microscope has recently been achieved at the nanometre scale. However,
converting these results to quantitative field measurements involves assumptions
whose validity is unclear for thick specimens. We consider three approaches to
quantitative reconstruction of the projected electric potential using segmented
detectors: a segmented detector approximation to differential phase contrast and
two variants on ptychographical reconstruction. Limitations to these approaches
are also studied, particularly errors arising from detector segment size,
inelastic scattering, and non-periodic boundary conditions. A simple calibration
experiment is described which corrects the differential phase contrast
reconstruction to give reliable quantitative results despite the finite detector
segment size and the effects of plasmon scattering in thick specimens. A plasmon
scattering correction to the segmented detector ptychography approaches is also
given. Avoiding the imposition of periodic boundary conditions on the
reconstructed projected electric potential leads to more realistic
reconstructions.
PMID- 28692935
TI - A direct comparison of experimental methods to measure dimensions of synthetic
nanoparticles.
AB - Nanoparticles have properties that depend critically on their dimensions. There
are a large number of methods that are commonly used to characterize these
dimensions, but there is no clear consensus on which method is most appropriate
for different types of nanoparticles. In this work four different
characterization methods that are commonly applied to characterize the dimensions
of nanoparticles either in solution or dried from solution are critically
compared. Namely, transmission electron microscopy (TEM), scanning electron
microscopy (SEM), atomic force microscopy (AFM), and dynamic light scattering
(DLS) are compared with one another. The accuracy and precision of the four
methods applied nanoparticles of different sizes composed of three different core
materials, namely gold, silica, and polystyrene are determined. The suitability
of the techniques to discriminate different populations of these nanoparticles in
mixtures are also studied. The results indicate that in general, scanning
electron microscopy is suitable for large nanoparticles (above 50 nm in
diameter), while AFM and TEM can also give accurate results with smaller
nanoparticles. DLS reveals details about the particles' solution dynamics, but is
inappropriate for polydisperse samples, or mixtures of differently sized samples.
SEM was also found to be more suitable to metallic particles, compared to oxide
based and polymeric nanoparticles. The conclusions drawn from the data in this
paper can help nanoparticle researchers choose the most appropriate technique to
characterize the dimensions of nanoparticle samples.
PMID- 28692936
TI - Tritium forms discrimination in ryegrass under constant tritium exposure: From
seed germination to seedling autotrophy.
AB - Uncertainties remain regarding the fate of atmospheric tritium after it has been
assimilated in grasslands (ryegrass) in the form of TFWT (Tissue Free Water
Tritium) or OBT (Organically Bound Tritium). One such uncertainty relates to the
tritium forms discrimination during transfer from TFWT to OBT resulting from
photosynthesis (OBTphoto), corresponding to the OBTphoto/TFWT ratio. In this
study, the OBT/TFWT ratio is determined by experiments in the laboratory using a
ryegrass model and hydroponic cultures, with constant activity of tritium in the
form of tritiated water (denoted as HTO) in the "water" compartment (liquid HTO)
and "air" compartment (HTO vapour in the air). The OBTphoto/TFWT ratio and the
exchangeable OBT fraction are measured for three parts of the plant: the leaf,
seed and root. Plant growth is modelled using dehydrated biomass measurements
taken over time in the laboratory and integrating physiological functions of the
plant during the first ten days after germination. The results suggest that there
is no measurable discrimination of tritium in the plant organic matter produced
by photosynthesis.
PMID- 28692937
TI - Phthalate esters and childhood asthma: A systematic review and congener-specific
meta-analysis.
AB - INTRODUCTION: Exposure to phthalate esters (PAEs) has been associated with
childhood asthma, but the congener-specific effects of PAEs on childhood asthma
were unclear. We aimed to systematically review and meta-analyze observational
studies on the associations between specific effects of PAEs and the risk of
childhood asthma. MATERIAL AND METHODS: Relevant studies were identified by
searching three databases up to October 20, 2016. The reference lists of the
retrieved articles were also reviewed. We included observational studies that
reported risk estimates with 95% confidence intervals (CIs) for the associations
between phthalate exposure and the risk of childhood asthma. Fixed-effects models
were generally applied to calculate pooled risk estimates. When heterogeneity was
present, random-effects models were applied. RESULTS: A total of nine studies
featuring 43 data points were included in our final meta-analyses. Results
indicated that the benzyl butyl phthalate (BBzP) exposure had a significant
association with the risk of childhood asthma. The Odd Ratios (ORs) were from
1.39 to 1.41 for different combination strategies. Subgroup analyses by different
exposure period or samples used showed that prenatal exposure to BBzP had a
stronger association with the risk of childhood asthma (OR = 1.38, 95% CI = 1.09
1.75), compared to those with postnatal exposure. Besides, the association was
evident when the phthalate exposure was measured from dust samples. The OR for
the associations between di-2-ethylhexyl phthalate (DEHP) in dust and childhood
asthma was 2.71 (95% CI = 1.39-5.28), and 2.08 (95% CI = 1.10-3.92) for BBzP.
CONCLUSIONS: Our study suggested a positive association between DEHP and BBzP
exposure and childhood asthma. Future studies are warranted to identify the
underlying mechanisms of the association.
PMID- 28692938
TI - Radioactive impacts on nekton species in the Northwest Pacific and humans more
than one year after the Fukushima nuclear accident.
AB - This study investigated the radioactive impacts on 10 nekton species in the
Northwest Pacific more than one year after the Fukushima Nuclear Accident (FNA)
from the two perspectives of contamination and harm. Squids were especially used
for the spatial and temporal comparisons to demonstrate the impacts from the FNA.
The radiation doses to nekton species and humans were assessed to link this
radioactivity contamination to possible harm. The total dose rates to nektons
were lower than the ERICA ecosystem screening benchmark of 10MUGy/h. Further dose
contribution analysis showed that the internal doses from the naturally occurring
nuclide 210Po were the main dose contributor. The dose rates from 134Cs, 137Cs,
90Sr and 110mAg were approximately three or four orders of magnitude lower than
those from naturally occurring radionuclides. The 210Po-derived dose was also the
main contributor of the total human dose from immersion in the seawater and the
ingestion of nekton species. The human doses from anthropogenic radionuclides
were ~ 100 to ~ 10,000 times lower than the doses from naturally occurring
radionuclides. A morbidity assessment was performed based on the Linear No
Threshold assumptions of exposure and showed 7 additional cancer cases per
100,000,000 similarly exposed people. Taken together, there is no need for
concern regarding the radioactive harm in the open ocean area of the Northwest
Pacific.
PMID- 28692939
TI - Oligomeric proanthocyanidin derived from grape seeds inhibited NF-kappaB
signaling in activated HSC: Involvement of JNK/ERK MAPK and PI3K/Akt pathways.
AB - In current study, we aimed to reveal the potential antifibrotic effects of
oligomeric proanthocyanidin (OPC) from grape seeds on lipopolysaccharide (LPS)
activated, HSC-T6, a rat hepatic stellate cell line. HSC-T6 cells were treated
with OPC 1h prior to LPS, and then incubated for indicated time. OPC inhibited
cells viability of HSC-T6 cells and decrease protein expression of collagen I,
alpha-smooth muscle actin (alpha-SMA), tissue inhibitors of metalloproteinases I
(TIMP-1) on LPS-induced HSC-T6 cells. OPC also significantly inhibited
phosphorylation of LPS-stimulated phosphatidylinositol 3-kinase (PI3K), protein
kinase B (Akt), extracellular signal-regulated kinase (ERK) and c-Jun N-terminal
kinase (JNK). Furthermore, OPC pretreatment blocked LPS-triggered nuclear factor
kappa B (NF-kappaB) translocation from cytosol to nuclear. OPC, as well as
specific inhibitors of NF-kappaB, PI3K and JNK could effectively inhibited alpha
SMA and collagen I expression. In conclusion, we demonstrated that the anti
fibrotic mechanism of OPC might be involved the inhibition of HSC activation and
transdifferentiation by suppressing NF-kappaB activation through JNK/ERK MAPK and
PI3K/Akt phosphorylation. Thus, OPC possesses the potential inhibitory property
of HSC activation through NF-kappaB modulation involving MAPK-PI3K/AKT pathways.
PMID- 28692940
TI - Betulinic acid and fluvastatin exhibits synergistic effect on toll-like receptor
4 mediated anti-atherogenic mechanism in type II collagen induced arthritis.
AB - Cardiovascular disease (CVD) is a major problem during rheumatoid arthritis which
leads to morbidity and mortality in arthritic patients. So the present study
emphasizes combinatorial effect of Betulinic acid, a triterpenoid and
fluvastatin, an HMG CoA reductase inhibitor on atherogenesis during arthritis.
Arthritis was induced by bovine type II collagen dissolved in 0.01M acetic acid
at a concentration of 4mg/mL and emulsified in equal volume of incomplete
Freund's adjuvant. Betulinic acid (2mg/kg) and fluvastatin (5mg/kg) alone and in
combination was administered orally from day 14 to 60. At the end of 60days,
tissues and blood were isolated for evaluation of biochemical parameters.
Treatment with betulinic acid and fluvastatin showed significant (p<0.05)
reduction in Arthritic index, Rheumatoid factor, C-reactive protein (CRP), total
lipids and anti-CCP (cyclic citrullinated peptide) antibody. Anti-inflammatory
enzyme activities and oxidative stress were significantly decreased in the
peripheral blood mononuclear cells by the administration of both betulinic acid
and fluvastatin than alone treatments. Combination therapy was found to be a
potential enhancer of the expression of anti-inflammatory cytokine interleukin-10
whereas it significantly blocked the expression of Toll-like receptors-2 and 4,
inflammatory markers such as interleukin-1beta, tumor necrosis factor-alpha,
Interferon-gamma, cell adhesion molecules and nuclear translocation of NF-kappa B
in aorta than drug alone treated groups. So the present study summarizes a
combination therapy of betulinic acid and fluvastatin that reduces the risk of
both rheumatoid arthritis and CVD by modulating the expression of various
inflammatory mediators through Toll-like receptors-4-NF-kappaB downstream
signaling pathway, atherogenic index and oxidative stress in collagen induced
arthritis.
PMID- 28692941
TI - Fibroblast growth factor 21 ameliorates high glucose-induced fibrogenesis in
mesangial cells through inhibiting STAT5 signaling pathway.
AB - Fibroblast growth factor 21 (FGF21) is a member of the FGF family and acts as a
potent regulator of glucose and lipid homeostasis, but its effect on renal
fibrosis and the underlying mechanisms are totally unknown. The purpose of this
study was designed to investigate whether FGF21 has effect on high glucose
induced fibrogenesis in human mesangial cells (HMCs) and the underlying
mechanism. High glucose is well known to stimulate the expression of extracelluar
matrix (ECM) in human mesangial cells. In humans, overexpression and deposition
of ECM lead to renal fibrosis. Thus, in this study, HMCs were incubated in high
glucose with or without various concentrations of FGF21. Results demonstrated
that the expression of FN, Col, TGF beta1 and alpha-SMA were significantly up
regulated in HMCs. Whereas, treatment with FGF21 down-regulated the expression of
FN, Col, TGF beta1 and alpha-SMA. In addition, growth factors are considered to
be an important driving force for the pathogenesis of renal fibrosis.
Significantly increased PDGF, VEGF and CTGF expression were found in HMCs induced
by high glucose. FGF21 treatments significantly decreased these growth factors
expression by down-regulating the phosphorylation level of STAT5. Here, we
reported for the first time that FGF21 decreases ECM expression by inhibiting
STAT5 signal pathway and consequently decreasing the expression of PDGF, VEGF and
CTGF.
PMID- 28692942
TI - Inter-species and intra-annual variations of moss nitrogen utilization:
Implications for nitrogen deposition assessment.
AB - Moss nitrogen (N) concentrations and natural 15N abundance (delta15N values) have
been widely employed to evaluate annual levels and major sources of atmospheric N
deposition. However, different moss species and one-off sampling were often used
among extant studies, it remains unclear whether moss N parameters differ with
species and different samplings, which prevented more accurate assessment of N
deposition via moss survey. Here concentrations, isotopic ratios of bulk carbon
(C) and bulk N in natural epilithic mosses (Bryum argenteum, Eurohypnum
leptothallum, Haplocladium microphyllum and Hypnum plumaeforme) were measured
monthly from August 2006 to August 2007 at Guiyang, SW China. The H. plumaeforme
had significantly (P < 0.05) lower bulk N concentrations and higher delta13C
values than other species. Moss N concentrations were significantly (P < 0.05)
lower in warmer months than in cooler months, while moss delta13C values
exhibited an opposite pattern. The variance component analyses showed that
different species contributed more variations of moss N concentrations and
delta13C values than different samplings. Differently, delta15N values did not
differ significantly between moss species, and its variance mainly reflected
variations of assimilated N sources, with ammonium as the dominant contributor.
These results unambiguously reveal the influence of inter-species and intra
annual variations of moss N utilization on N deposition assessment.
PMID- 28692943
TI - Progressive increase in point mutations associates chloroquine resistance: Even
after withdrawal of chloroquine use in India.
AB - Chloroquine (CQ) is highly effective against P. vivax, due to the rapid spread of
CQ resistance in P. falciparum parasites; it is no longer the drug of choice
against P. falciparum. This study elucidates the scenario of chloroquine efficacy
at times that coincided with a new drug policy and especially assessed the
chloroquine resistant molecular markers after withdrawal of chloroquine in
Kolkata and Purulia, two malaria endemic zones of West Bengal, India. In vitro CQ
susceptibility was tested in 781 patients with P. falciparum mono infections
between 2008 and 2013, of which 338 patients had received CQ in 2008-2009.
Genotyping of the pfcrt and the pfmdr1 gene was carried out in all isolates.
Early treatment failure was detected in 114 patients {43 (31.39%) from Kolkata
and 71 (35.32%) from Purulia} while recrudescence was identified in 13 (9.49%)
and 17 (8.46%) patients from Kolkata and Purulia respectively. In vivo
chloroquine resistance was strongly associated with CVMNT-YYSNY (p < 0.01) and
SVMNT-YYSNY (p < 0.05) allele in Kolkata. In Purulia chloroquine resistance was
associated with CVMNK-YYSNY (P < 0.005), SVMNT-YYSNY (P < 0.01) allele. The
proportion of in vitro chloroquine resistance increased in subsequent years to
87.23% and 93.10% in 2013, in Kolkata and Purulia, respectively. Isolates with
SVMNT-YFSND, SVMNT-YFSNY, CVIET-YFSND and CVIET-YYSNY haplotypes increased
gradually (p < 0.05) from 2010 to 2013, leading to a rise in IC50 (p < 0.05) of
chloroquine. An increase in in vitro chloroquine resistance and candidate gene
mutations even after five years of chloroquine withdrawal against P. falciparum
calls for synchronized research surveillance and proper containment strategies.
PMID- 28692944
TI - Kinetics-mediate fabrication of multi-model bioimaging lanthanide nanoplates with
controllable surface roughness for blood brain barrier transportation.
AB - Effective delivery of imaging agents or therapeutics to the brain has remained
elusive due to the poor blood-brain barrier (BBB) permeability, resulting in the
apparent risks of inefficient diagnosis and therapeutic agents for brain disease.
Herein, we report on the surface roughness mediated BBB transportation for the
first time. The lanthanide-based core/shell/shell structured
NaYF4:Yb,Er@NaGdF4:Yb@NaNdF4:Yb nanoplates with controllable surface roughness
and multi-model bioimaging features were synthesized and used to evaluate the
surface roughness dependent BBB permeability without any surface bio
functionalization. By controlling the kinetics of the shell coating process, the
hexagon-disc, multi-petals and six-petals nanoplates with different surface
roughness can be obtained. Comparing with the NPs with less Ra and receptor
conjugated NPs, the obtained six-petals nanoplates with highest roughness exhibit
excellent performance in BBB transportation and tumor targeting, which lay solid
foundation for the diagnosis and the therapy of brain tumor.
PMID- 28692945
TI - Impact of New York prescription drug monitoring program, I-STOP, on statewide
overdose morbidity.
AB - BACKGROUND: Prescription Drug Monitoring programs (PDMPs) are intended to reduce
opioid prescribing and aberrant drug-related behavior thereby reducing morbidity
and mortality due to prescription opioid overdose. Expansion of the New York (NY)
State's PDMP in 2013 included the institution of the I-STOP law that mandated
clinicians to consult the statewide PDMP database to review the patient's
prescription history prior to prescribing opioids. METHODS: Trends in
prescription opioid distribution, prescribing, and prescription opioid and heroin
overdose morbidity in NY were analyzed using time series. A Chow test was used to
test the difference in trends before and after the implementation of I-STOP.
RESULTS: The results indicated that: 1) the number of opioid prescriptions
appears to be declining following the implementation of the I-STOP, 2) however,
supply chain data shows that the total quantity of opioids in the supply chain
increased, 3) statewide trends in inpatient and emergency department visits for
prescription opioid overdose increased from 2010 to the third quarter of 2013
where the slope leveled off following I-STOP, but this change in slope was not
significant, 4) visits for heroin overdose started escalating in 2010 and
continued to increase through the second quarter of 2016. The overall
significance of these findings show a small impact of PDMPs on prescription
opioid overdose morbidity in NY in the context of the increasing national trend
during this time period. CONCLUSIONS: Prescription opioid morbidity leveled off
following the implementation of a mandated PDMP although morbidity attributable
to heroin overdose continued to rise.
PMID- 28692946
TI - Victimization as a mediator of alcohol use disparities between sexual minority
subgroups and sexual majority youth using the 2015 National Youth Risk Behavior
Survey.
AB - BACKGROUND: Alcohol use among underage youth is a significant public health
concern. According to the National Institute on Alcohol Abuse and Alcoholism,
alcohol is the "drug of choice" among adolescents, meaning more youth use and
abuse alcohol than any other substance. Prevalence of alcohol use is
disproportionately higher among sexual minority youth (SMY) than among their
heterosexual peers. We examined sexual identity and sexual behavior disparities
in alcohol use, and the mediational role of bullying in a sample of high school
students. METHODS: Data from the 2015 National Youth Risk Behavior Survey were
used to assess the association between sexual minority status (identity and
behavior) and alcohol use with weighted logistic regression. Due to well
documented differences between males and females, we stratified models by gender.
Physical and cyberbullying were examined as mediators of the relationship between
sexual minority status and alcohol use. RESULTS: We detected associations between
certain subgroups of sexual minority youth and alcohol use across all four
drinking variables (ever drank alcohol, age at first drink, current alcohol use,
and binge drinking). Most of these associations were found among bisexual
identified youth and students with both male and female sexual partners; these
individuals had up to twice the odds of engaging in alcohol use behaviors when
compared with sexual majority students. Associations were strongest among
females. Bullying mediated sexual minority status and alcohol use only among
bisexual females. CONCLUSIONS: As disparities in alcohol use differ by gender,
sexual identity, and sexual behavior, interventions should be targeted
accordingly.
PMID- 28692947
TI - How services for children with disabilities in Serbia affect the quality of life
of their families.
AB - BACKGROUND: Families that have children with disabilities face numerous
difficulties related to the lack of services support, social isolation and
poverty in Serbia. Mostly due to the prolonged effect of social and economic
crisis, there are insufficient adequate and diverse community-based services for
those families. AIMS: The aim of the study was to examine the effect of newly
introduced services on the quality of families' life. METHODS: A pretest/posttest
study was conducted at the beginning of service and one year later to evaluate
the effect of services measured by Family Quality of Life Scale (Hoffman et al.,
2006). The sample consists of 153 families of children with disabilities from 35
different places in Serbia. RESULTS: The results show that the services generally
improved the families' quality of life, particularly in the aspects targeted by
services, but also had significant positive effect on family interaction and
parenting. The services had the highest impact on the families that perceived the
lowest life quality before using them. The life quality was improved, regardless
of the type of services, but the effectiveness is affected by the severity of
child disability. IMPLICATIONS: The results might be useful for further steps in
developing and evaluating individually and flexible tailored service that support
families' needs and suits them the best.
PMID- 28692948
TI - Parenting children with down syndrome: An analysis of parenting styles, parenting
dimensions, and parental stress.
AB - BACKGROUND: Effective parenting is vital for a child's development. Although much
work has been conducted on parenting typically developing children, little work
has examined parenting children with Down syndrome. AIMS: The purpose of the
current study was to compare the parenting styles and dimensions in mothers of
children with DS and mothers of TD children. METHODS AND PROCEDURES: Thirty-five
mothers of children with DS and 47 mothers of TD children completed
questionnaires about parenting, parental stress, child behavior problems, and
child executive function. OUTCOMES AND RESULTS: We found that mothers of children
with DS use an authoritative parenting style less and a permissive parenting
style more than mothers of TD children. Additionally, we found that mothers of
children with DS use reasoning/induction and verbal hostility less and ignoring
misbehavior more than mothers of TD children. All of these differences, except
for those of reasoning/induction, were at least partially accounted for by the
higher levels of parental stress in the DS group. CONCLUSIONS AND IMPLICATIONS:
Parenting interventions should be focused on reducing parental stress and
training mothers to parent under stress in an effort to improve parenting
techniques, which would, in theory, improve long-term child outcomes for children
with DS.
PMID- 28692949
TI - Adjuvant interferon-alpha for the treatment of high-risk melanoma: An individual
patient data meta-analysis.
AB - BACKGROUND: Many randomised trials assessing interferon-alpha (IFN-alpha) as
adjuvant therapy for high-risk malignant melanoma have been undertaken. To better
assess the role of IFN-alpha, an individual patient data (IPD) meta-analysis of
these trials was undertaken. METHODS: IPD was sought from all randomised trials
of adjuvant IFN-alpha versus no IFN-alpha for high-risk melanoma. Primary
outcomes were event-free survival (EFS) and overall survival (OS). Standard
methods for quantitative IPD meta-analysis were used. Subgroup analyses by dose,
duration of treatment and various patient and disease-specific parameters were
performed. FINDINGS: Fifteen trials were included in the analysis (eleven with
IPD). EFS was significantly improved with IFN-alpha (hazard ratio [HR] = 0.86, CI
0.81-0.91; P < 0.00001), as was OS (HR = 0.90, CI 0.85-0.97; P = 0.003). The
absolute differences in EFS at 5 and 10 years were 3.5% and 2.7%, and for OS were
3.0% and 2.8% respectively in favour of IFN-alpha. There was no evidence that the
benefit of IFN-alpha differed depending on dose or duration of treatment, or by
age, gender, site of primary tumour, disease stage, Breslow thickness, or
presence of clinical nodes. Only for ulceration was there evidence of an
interaction (test for heterogeneity: P = 0.04 for EFS; P = 0.002 for OS); only
patients with ulcerated tumours appeared to obtain benefit from IFN-alpha.
CONCLUSION: This meta-analysis provides clear evidence that adjuvant IFN-alpha
significantly reduces the risk of relapse and improves survival and shows no
benefit for higher doses compared to lower doses. The increased benefit in
patients with ulcerated tumours, and lack of benefit in patients without
ulceration, needs further investigation.
PMID- 28692950
TI - Preoperative breast radiation therapy: Indications and perspectives.
AB - Preoperative breast radiation therapy (RT) is not a new concept, but older
studies failed to change practice. More recently, there has been interest in
revisiting preoperative RT using modern techniques. This current perspective
discusses the indications, summarises the published literature and then
highlights current clinical trials, with particular attention to combining with
novel drugs and optimising associated translational research.
PMID- 28692951
TI - Identifying critical steps towards improved access to innovation in cancer care:
a European CanCer Organisation position paper.
AB - In recent decades cancer care has seen improvements in the speed and accuracy of
diagnostic procedures; the effectiveness of surgery, radiation therapy and
medical treatments; the power of information technology; and the development of
multidisciplinary, specialist-led approaches to care. Such innovations are
essential if we are to continue improving the lives of cancer patients across
Europe despite financial pressures on our healthcare systems. Investment in
innovation must be balanced with the need to ensure the sustainability of
healthcare budgets, and all health professionals have a responsibility to help
achieve this balance. It requires scrutiny of the way care is delivered; we must
be ready to discontinue practices or interventions that are inefficient, and
prioritise innovations that may deliver the best outcomes possible for patients
within the limits of available resources. Decisions on innovations should take
into account their long-term impact on patient outcomes and costs, not just their
immediate costs. Adopting a culture of innovation requires a multidisciplinary
team approach, with the patient at the centre and an integral part of the team.
It must take a whole-system and whole-patient perspective on cancer care and be
guided by high-quality real-world data, including outcomes relevant to the
patient and actual costs of care; this accurately reflects the impact of any
innovation in clinical practice. The European CanCer Organisation is committed to
working with its member societies, patient organisations and the cancer community
at large to find sustainable ways to identify and integrate the most meaningful
innovations into all aspects of cancer care.
PMID- 28692952
TI - Translation and psychometric properties of a Spanish version of the College
Alcohol Problems Scale.
AB - Hispanic and Spanish-speaking college students are under-represented in alcohol
intervention and prevention research. There is a need for brief, empirically
validated Spanish versions of measures related to alcohol use and consequences.
The objective of this study was to translate the 8-item College Alcohol Problems
Scale (CAPS) into Spanish and evaluate the psychometric properties of this
measure compared to the original English. Bilingual experts in interventions for
Hispanic college students and youth used a translation back-translation process.
125 Hispanic undergraduate students from a large southeastern public university
completed the CAPS and a heavy drinking measure in Spanish. The two-factor model
had acceptable model fit in Spanish, chi2 (df=19)=27.60, p=0.091; CFI=0.966
RMSEA=0.060. Internal consistency of the personal problems subscale was 0.76, and
the social problems subscale was 0.73. The two latent factors explained 24-66% of
variability in items. Personal problems and social problems were both
significantly correlated with heavy drinking, r=0.61, p<0.001, r=0.59, p<0.001,
respectively. This Spanish version of the CAPS is a reliable and valid measure of
consequences of alcohol use, and has similar psychometric properties to the
original English version. This measure may be useful for future research,
intervention, and prevention with samples of U.S. Hispanic college students or
Spanish-speaking students in other nations.
PMID- 28692953
TI - Motivations for reducing alcohol consumption: An international survey exploring
experiences that may lead to a change in drinking habits.
AB - AIMS: Brief interventions delivered by doctors and other healthcare practitioners
might be meaningfully enhanced by understanding what individual experiences might
lead patients to cut down. The aim of the current paper was to explore the
experiences that might lead people to reduce their alcohol consumption and to
compare these findings between respondents from 21 different countries. METHODS:
Global Drug Survey is an online cross sectional, opportunistic anonymous survey.
This paper includes 72,209 respondents from 21 counties with over 250 respondents
(60.8% male). RESULTS: Almost a third (32.9%) of participants reported that they
would like to drink less alcohol over the next 12months, and a third thought
their GP would tell them to cut down if they were honest about their drinking.
The primary experiences that were rated as most likely to lead to a change in
behaviour were related to physical health, sexual assault and having to seek
emergency medical treatment. Respondents from Germany were more likely to select
embarrassment as a motivation to reduce drinking than those from other counties.
Females were more likely to report indicate motivations related to sexual regret,
sexual assault or seeking treatment. Older participants and those in the low risk
audit category were more likely to report embarrassment or forgetfulness as
potential motivation for change. CONCLUSION: Understanding the different
motivations that may lead individuals to change their drinking behaviours can be
used to inform targeted brief interventions and targeted public health guidance.
PMID- 28692954
TI - Process variables predicting changes in adolescent alcohol consumption and mental
health symptoms following personality-targeted interventions.
AB - OBJECTIVE: This study aims to identify key process variables that are associated
with changes in alcohol consumption and mental health symptoms over 12months
following personality-targeted interventions in youth. METHOD: 154 high-risk
youth (aged 12-13years) in 7 Montreal high schools were identified using the
Substance Use Risk Profile Scale and participated in personality-matched
interventions. Preliminary process variables were identified using a combination
of psychotherapy process variables and youth-generated (qualitative) feedback
immediately post-intervention. RESULTS: Learning, skill development and a
positive group experience were key to positive behavioural change. Youth
generated feedback independently accounted for 12-25% of the variance in the
change in alcohol use and mental health symptoms over 12months. Changes in
cognitive distortions and self-esteem accounted for somewhat less of the variance
in alcohol use (0-9%), but a moderate-to-large portion of the variance in changes
in mental health symptoms (up to 44%). CONCLUSIONS: The study findings highlight
candidate process variables relevant to future implementations of this program
that might inform change processes relevant to brief interventions with youth
more generally. This study suggests that youth experiences can indicate proximal
measures of program efficacy, and has implications for the dissemination of this
brief intervention program. Clinical Trial registered on www.ClinicalTrials.gov,
"Does Delaying Adolescent Substance Use Lead to Improved Cognitive Function and
Reduce Risk for Addiction", study NCT01655615.
PMID- 28692955
TI - Ethnic density and risk of mental ill health - The case of religious sectarianism
in Northern Ireland: A population data linkage study.
AB - An ethnic group that lives in a neighbourhood in which it is in the minority,
termed 'lower ethnic density,' tends to report a higher incidence of mental ill
health. This population-based study investigated for the first time the existence
of an own-group density effect among Catholic and Protestant communities in
Northern Ireland. The entire Northern Ireland born Catholic and Protestant
working age (n = 1, 004,060) enumerated population in the 2011 Census of Northern
Ireland were included in the study via administrative data-linkage methodology.
Catholics had a greater likelihood of reporting mental ill health in
neighbourhoods with the largest proportion of Catholics (OR = 1.25, 95%CI 1.07
1.47), whereas mental health among Protestants was not associated with
neighbourhood proportion of Protestants, after adjusting for socio-economic
status and neighbourhood deprivation. The results indicate that a complex
relationship exists between group identity, population composition of ethnic and
religious groups and prevalence of community mental health.
PMID- 28692956
TI - DeepFix: A Fully Convolutional Neural Network for Predicting Human Eye Fixations.
AB - Understanding and predicting the human visual attention mechanism is an active
area of research in the fields of neuroscience and computer vision. In this
paper, we propose DeepFix, a fully convolutional neural network, which models the
bottom-up mechanism of visual attention via saliency prediction. Unlike classical
works, which characterize the saliency map using various hand-crafted features,
our model automatically learns features in a hierarchical fashion and predicts
the saliency map in an end-to-end manner. DeepFix is designed to capture
semantics at multiple scales while taking global context into account, by using
network layers with very large receptive fields. Generally, fully convolutional
nets are spatially invariant-this prevents them from modeling location-dependent
patterns (e.g., centre-bias). Our network handles this by incorporating a novel
location-biased convolutional layer. We evaluate our model on multiple
challenging saliency data sets and show that it achieves the state-of-the-art
results.
PMID- 28692957
TI - Passive Wearable Skin Patch Sensor Measures Limb Hemodynamics Based on
Electromagnetic Resonance.
AB - OBJECTIVE: The objectives of this study were to design and develop an open
circuit electromagnetic resonant skin patch sensor, characterize the fluid volume
and resonant frequency relationship, and investigate the sensor's ability to
measure limb hemodynamics and pulse volume waveform features. METHODS: The skin
patch was designed from an open-circuit electromagnetic resonant sensor comprised
of a single baseline trace of copper configured into a square planar spiral which
had a self-resonating response when excited by an external radio frequency sweep.
Using a human arm phantom with a realistic vascular network, the sensor's
performance to measure limb hemodynamics was evaluated. RESULTS: The sensor was
able to measure pulsatile blood flow which registered as shifts in the sensor's
resonant frequencies. The time-varying waveform pattern of the resonant frequency
displayed a systolic upstroke, a systolic peak, a dicrotic notch, and a diastolic
down stroke. The resonant frequency waveform features and peak systolic time were
validated against ultrasound pulse wave Doppler. A statistical correlation
analysis revealed a strong correlation () between the resonant sensor peak
systolic time and the pulse wave Doppler peak systolic time. CONCLUSION: The
sensor was able to detect pulsatile flow, identify hemodynamic waveform features,
and measure heart rate with 98% accuracy. SIGNIFICANCE: The open-circuit resonant
sensor design leverages the architecture of a thin planar spiral which is passive
(does not require batteries), robust and lightweight (does not have electrical
components or electrical connections), and may be able to wirelessly monitor
cardiovascular health and limb hemodynamics.
PMID- 28692958
TI - GriFT: A Device for Quantifying Physiological and Pathological Mirror Movements
in Children.
AB - GOAL: Mirror movements (MM) occur during unilateral actions and manifest as
involuntary muscle activity of the passive limb, "mirroring" voluntary actions
executed by the contralateral homologous body part. They are a normal motor
feature in young children that gradually disappears. In children suffering from
neurological disorders, e.g., unilateral cerebral palsy, MMs have been proposed
to yield relevant information for diagnosis and therapy. However, in clinical
practice, MM are typically assessed using an ordinal rating scale. Here, we
introduce the grip force tracking (GriFT) device, a portable system to
quantitatively assess MM during repetitive unimanual squeezing while playing a
computer game. METHODS: The GriFT device consists of two handles, each equipped
with two compressive force sensors (range 0-23 kg, Fz 1000 Hz). Children complete
three trials of unimanual squeezing, whereby the visual display on the screen
determines the squeezing rhythm (0.67 Hz at 15% maximum voluntary contraction,
force-level adjusted per hand). MMs are characterized based on frequency,
amplitude, and temporal features (synchronization, timing). RESULTS: MM differed
significantly between children with different clinical MM scores. MM frequency
and amplitude were most discriminative. Categorization of physiological MM proved
highly sensitive (89%-97%). CONCLUSION: We demonstrated feasibility and validity
of the GriFT device in a large cohort of typically developing children (N = 174,
age 5-15 years), and its clinical applicability in children with unilateral
cerebral palsy with various levels of hand function. SIGNIFICANCE: The
quantification of MM is a promising tool to further investigate and categorize MM
in children with unilateral cerebral palsy.
PMID- 28692959
TI - Dedicated Entropy Measures for Early Assessment of Pregnancy Progression From
Single-Channel Electrohysterography.
AB - OBJECTIVE: Preterm birth is a large-scale clinical problem involving over 10% of
infants. Diagnostic means for timely risk assessment are lacking and the
underlying physiological mechanisms unclear. To improve the evaluation of
pregnancy before term, we introduce dedicated entropy measures derived from a
single-channel electrohysterogram (EHG). METHODS: The estimation of approximate
entropy (ApEn) and sample entropy (SampEn) is adjusted to monitor variations in
the regularity of single-channel EHG recordings, reflecting myoelectrical changes
due to pregnancy progression. In particular, modifications in the tolerance
metrics are introduced for improving robustness to EHG amplitude fluctuations. An
extensive database of 58 EHG recordings with 4 monopolar channels in women
presenting with preterm contractions was manually annotated and used for
validation. The methods were tested for their ability to recognize the onset of
labor and the risk of preterm birth. Comparison with the best single-channel
methods according to the literature was performed. RESULTS: The reference methods
were outperformed. SampEn and ApEn produced the best prediction of delivery,
although only one channel showed a significant difference () between labor and
nonlabor. The modified ApEn produced the best prediction of preterm delivery,
showing statistical significance () in three channels. These results were also
confirmed by the area under the receiver operating characteristic curve and
fivefold cross validation. CONCLUSION: The use of dedicated entropy estimators
improves the diagnostic value of EHG analysis earlier in pregnancy. SIGNIFICANCE:
Our results suggest that changes in the EHG might manifest early in pregnancy,
providing relevant prognostic opportunities for pregnancy monitoring by a
practical single-channel solution.
PMID- 28692960
TI - Sequential Therapeutic Response Modeling for Tumor Treatment Using Computational
Hybrid Control Systems Approach.
AB - OBJECTIVE: Tumorigenesis is due to uncontrolled cell division arising from
mutations and alterations in the proliferative controls of the cell population.
The fight against tumor growth and development has often relied on combination
therapy that has been acclaimed as one of the main standards of care in cancer
therapeutics and prevention of drug-related resistances. The toxicity of the
combinatorial drugs raises a significant concern whenever patients take two or
more drugs concurrently at the maximum tolerated dose. A promising solution in
tumor treatment involves the administration of the drugs in an alternating or
sequential fashion rather than a simultaneous manner. In this paper, we
investigate how feasible such an approach is from a mathematical perspective and
propose a switched hybrid control systems framework. METHODS: We explore the
response of tumor cells dynamics to sequential drugs administration with the aid
of a time-dependent switching strategy. A transit compartmentalized model is
employed to describe the tumor cells progression to death. RESULTS: The design of
the time-based drug switching logic ensures the proliferating tumor cells are
repressed. CONCLUSIONS: Simulation results are provided using the tumor growth
dynamics with sequential drugs intake to demonstrate the effectiveness of the
proposed method in reducing the tumor size. SIGNIFICANCE: This paper is the first
attempt to provide a switched hybrid control systems framework on sequential drug
administration to biomedical researchers and clinicians.
PMID- 28692961
TI - Places: A 10 Million Image Database for Scene Recognition.
AB - The rise of multi-million-item dataset initiatives has enabled data-hungry
machine learning algorithms to reach near-human semantic classification
performance at tasks such as visual object and scene recognition. Here we
describe the Places Database, a repository of 10 million scene photographs,
labeled with scene semantic categories, comprising a large and diverse list of
the types of environments encountered in the world. Using the state-of-the-art
Convolutional Neural Networks (CNNs), we provide scene classification CNNs
(Places-CNNs) as baselines, that significantly outperform the previous
approaches. Visualization of the CNNs trained on Places shows that object
detectors emerge as an intermediate representation of scene classification. With
its high-coverage and high-diversity of exemplars, the Places Database along with
the Places-CNNs offer a novel resource to guide future progress on scene
recognition problems.
PMID- 28692962
TI - Bilinear Convolutional Neural Networks for Fine-grained Visual Recognition.
AB - We present a simple and effective architecture for fine-grained recognition
called Bilinear Convolutional Neural Networks (B-CNNs). These networks represent
an image as a pooled outer product of features derived from two CNNs and capture
localized feature interactions in a translationally invariant manner. B-CNNs are
related to orderless texture representations built on deep features but can be
trained in an end-to-end manner. Our most accurate model obtains 84.1%, 79.4%,
84.5% and 91.3% per-image accuracy on the Caltech-UCSD birds [66], NABirds [63],
FGVC aircraft [42], and Stanford cars [33] dataset respectively and runs at 30
frames-per-second on a NVIDIA Titan X GPU. We then present a systematic analysis
of these networks and show that (1) the bilinear features are highly redundant
and can be reduced by an order of magnitude in size without significant loss in
accuracy, (2) are also effective for other image classification tasks such as
texture and scene recognition, and (3) can be trained from scratch on the
ImageNet dataset offering consistent improvements over the baseline architecture.
Finally, we present visualizations of these models on various datasets using top
activations of neural units and gradient-based inversion techniques. The source
code for the complete system is available at http://vis-www.cs.umass.edu/bcnn.
PMID- 28692963
TI - Learning from Ambiguously Labeled Face Images.
AB - Learning a classifier from ambiguously labeled face images is challenging since
training images are not always explicitly-labeled. For instance, face images of
two persons in a news photo are not explicitly labeled by their names in the
caption. We propose a Matrix Completion for Ambiguity Resolution (MCar) method
for predicting the actual labels from ambiguously labeled images. This step is
followed by learning a standard supervised classifier from the disambiguated
labels to classify new images. To prevent the majority labels from dominating the
result of MCar, we generalize MCar to a weighted MCar (WMCar) that handles label
imbalance. Since WMCar outputs a soft labeling vector of reduced ambiguity for
each instance, we can iteratively refine it by feeding it as the input to WMCar.
Nevertheless, such an iterative implementation can be affected by the noisy soft
labeling vectors, and thus the performance may degrade. Our proposed Iterative
Candidate Elimination (ICE) procedure makes the iterative ambiguity resolution
possible by gradually eliminating a portion of least likely candidates in
ambiguously labeled faces. We further extend MCar to incorporate the labeling
constraints among instances when such prior knowledge is available. Compared to
existing methods, our approach demonstrates improvements on several ambiguously
labeled datasets.
PMID- 28692964
TI - Joint Semantic and Latent Attribute Modelling for Cross-Class Transfer Learning.
AB - A number of vision problems such as zero-shot learning and person re
identification can be considered as cross-class transfer learning problems. As
mid-level semantic properties shared cross different object classes, attributes
have been studied extensively for knowledge transfer across classes. Most
previous attribute learning methods focus only on human-defined/nameable semantic
attributes, whilst ignoring the fact there also exist undefined/latent shareable
visual properties, or latent attributes. These latent attributes can be either
discriminative or non-discriminative parts depending on whether they can
contribute to an object recognition task. In this work, we argue that learning
the latent attributes jointly with user-defined semantic attributes not only
leads to better representation but also helps semantic attribute prediction. A
novel dictionary learning model is proposed which decomposes the dictionary space
into three parts corresponding to semantic, latent discriminative and latent
background attributes respectively. Such a joint attribute learning model is then
extended by following a multi-task transfer learning framework to address a more
challenging unsupervised domain adaptation problem, where annotations are only
available on an auxiliary dataset and the target dataset is completely
unlabelled. Extensive experiments show that the proposed models, though being
linear and thus extremely efficient to compute, produce state-of-the-art results
on both zero-shot learning and person re-identification.
PMID- 28692965
TI - 3D Reconstruction in the Presence of Glass and Mirrors by Acoustic and Visual
Fusion.
AB - We present a practical and inexpensive method to reconstruct 3D scenes that
include transparent and mirror objects. Our work is motivated by the need for
automatically generating 3D models of interior scenes, which commonly include
glass. These large structures are often invisible to cameras or even to our human
visual system. Existing 3D reconstruction methods for transparent objects are
usually not applicable in such a room-sized reconstruction setting. Our simple
hardware setup augments a regular depth camera (e.g., the Microsoft Kinect
camera) with a single ultrasonic sensor, which is able to measure the distance to
any object, including transparent surfaces. The key technical challenge is the
sparse sampling rate from the acoustic sensor, which only takes one point
measurement per frame. To address this challenge, we take advantage of the fact
that the large scale glass structures in indoor environments are usually either
piece-wise planar or a simple parametric surface. Based on these assumptions, we
have developed a novel sensor fusion algorithm that first segments the (hybrid)
depth map into different categories such as opaque/transparent/infinity (e.g.,
too far to measure) and then updates the depth map based on the segmentation
outcome. We validated our algorithms with a number of challenging cases,
including multiple panes of glass, mirrors, and even a curved glass cabinet.
PMID- 28692966
TI - Learning Semantic Part-Based Models from Google Images.
AB - We propose a technique to train semantic part-based models of object classes from
Google Images. Our models encompass the appearance of parts and their spatial
arrangement on the object, specific to each viewpoint. We learn these rich models
by collecting training instances for both parts and objects, and automatically
connecting the two levels. Our framework works incrementally, by learning from
easy examples first, and then gradually adapting to harder ones. A key benefit of
this approach is that it requires no manual part location annotations. We
evaluate our models on the challenging PASCAL-Part dataset [1] and show how their
performance increases at every step of the learning, with the final models more
than doubling the performance of directly training from images retrieved by
querying for part names (from 12.9 to 27.2 AP). Moreover, we show that our part
models can help object detection performance by enriching the R-CNN detector with
parts.
PMID- 28692967
TI - Phase Vector Incompressible Registration Algorithm for Motion Estimation From
Tagged Magnetic Resonance Images.
AB - Tagged magnetic resonance imaging has been used for decades to observe and
quantify motion and strain of deforming tissue. It is challenging to obtain 3-D
motion estimates due to a tradeoff between image slice density and acquisition
time. Typically, interpolation methods are used either to combine 2-D motion
extracted from sparse slice acquisitions into 3-D motion or to construct a dense
volume from sparse acquisitions before image registration methods are applied.
This paper proposes a new phase-based 3-D motion estimation technique that first
computes harmonic phase volumes from interpolated tagged slices and then matches
them using an image registration framework. The approach uses several concepts
from diffeomorphic image registration with a key novelty that defines a symmetric
similarity metric on harmonic phase volumes from multiple orientations. The
material property of harmonic phase solves the aperture problem of optical flow
and intensity-based methods and is robust to tag fading. A harmonic magnitude
volume is used in enforcing incompressibility in the tissue regions. The
estimated motion fields are dense, incompressible, diffeomorphic, and inverse
consistent at a 3-D voxel level. The method was evaluated using simulated
phantoms, human brain data in mild head accelerations, human tongue data during
speech, and an open cardiac data set. The method shows comparable accuracy to
three existing methods while demonstrating low computation time and robustness to
tag fading and noise.
PMID- 28692968
TI - Intravascular Ultrasound Imaging With Virtual Source Synthetic Aperture Focusing
and Coherence Factor Weighting.
AB - Intravascular ultrasound (IVUS) has been frequently used for coronary artery
imaging clinically. More importantly, IVUS is the fundamental image modality for
most advanced multimodality intravascular imaging techniques, since it provides a
more comprehensive picture of vessel anatomy on which other imaging data can be
superimposed. However, image quality in the deeper region is poor because of the
downgraded lateral resolution and contrast-to-noise ratio (CNR). In this paper,
we report on the application of an ultrasound beamforming method that combines
virtual source synthetic aperture (VSSA) focusing and coherence factor weighting
(CFW) to improve the IVUS image quality. The natural focal point of conventional
IVUS transducer was treated as a virtual source that emits spherical waves within
a certain region. Mono-static synthetic aperture focusing was conducted to
achieve higher resolution. Coherence factor was calculated using delayed RF
signals and applied to the synthesized beam to increase the CNR and focusing
quality. The proposed method was tested through simulations in Field II and
imaging experiments in both linear and rotational scans. The lateral resolution
for linear scan mode is improved from 165-524 to 126-143 MUm ; resolution for
rotational scan mode improves by up to 42%. CNR improvement by up to 1.5 was
observed on the anechoic cysts of different sizes and at different locations.
Herein, it is demonstrated that the beamforming method, which combines VSSA and
CFW, can significantly improve the IVUS image quality. This approach can be
readily integrated into the current IVUS imaging system for enhanced clinical
diagnosis.
PMID- 28692969
TI - An MR-Based Model for Cardio-Respiratory Motion Compensation of Overlays in X-Ray
Fluoroscopy.
AB - In X-ray fluoroscopy, static overlays are used to visualize soft tissue. We
propose a system for cardiac and respiratory motion compensation of these
overlays. It consists of a 3-D motion model created from real-time magnetic
resonance (MR) imaging. Multiple sagittal slices are acquired and retrospectively
stacked to consistent 3-D volumes. Slice stacking considers cardiac information
derived from the ECG and respiratory information extracted from the images.
Additionally, temporal smoothness of the stacking is enhanced. Motion is
estimated from the MR volumes using deformable 3-D/3-D registration. The motion
model itself is a linear direct correspondence model using the same surrogate
signals as slice stacking. In X-ray fluoroscopy, only the surrogate signals need
to be extracted to apply the motion model and animate the overlay in real time.
For evaluation, points are manually annotated in oblique MR slices and in
contrast-enhanced X-ray images. The 2-D Euclidean distance of these points is
reduced from 3.85 to 2.75 mm in MR and from 3.0 to 1.8 mm in X-ray compared with
the static baseline. Furthermore, the motion-compensated overlays are shown
qualitatively as images and videos.
PMID- 28692970
TI - A Kernel-Based Low-Rank (KLR) Model for Low-Dimensional Manifold Recovery in
Highly Accelerated Dynamic MRI.
AB - While many low rank and sparsity-based approaches have been developed for
accelerated dynamic magnetic resonance imaging (dMRI), they all use low rankness
or sparsity in input space, overlooking the intrinsic nonlinear correlation in
most dMRI data. In this paper, we propose a kernel-based framework to allow
nonlinear manifold models in reconstruction from sub-Nyquist data. Within this
framework, many existing algorithms can be extended to kernel framework with
nonlinear models. In particular, we have developed a novel algorithm with a
kernel-based low-rank model generalizing the conventional low rank formulation.
The algorithm consists of manifold learning using kernel, low rank enforcement in
feature space, and preimaging with data consistency. Extensive simulation and
experiment results show that the proposed method surpasses the conventional low
rank-modeled approaches for dMRI.
PMID- 28692971
TI - Constrained Deep Weak Supervision for Histopathology Image Segmentation.
AB - In this paper, we develop a new weakly supervised learning algorithm to learn to
segment cancerous regions in histopathology images. This paper is under a
multiple instance learning (MIL) framework with a new formulation, deep weak
supervision (DWS); we also propose an effective way to introduce constraints to
our neural networks to assist the learning process. The contributions of our
algorithm are threefold: 1) we build an end-to-end learning system that segments
cancerous regions with fully convolutional networks (FCNs) in which image-to
image weakly-supervised learning is performed; 2) we develop a DWS formulation to
exploit multi-scale learning under weak supervision within FCNs; and 3)
constraints about positive instances are introduced in our approach to
effectively explore additional weakly supervised information that is easy to
obtain and enjoy a significant boost to the learning process. The proposed
algorithm, abbreviated as DWS-MIL, is easy to implement and can be trained
efficiently. Our system demonstrates the state-of-the-art results on large-scale
histopathology image data sets and can be applied to various applications in
medical imaging beyond histopathology images, such as MRI, CT, and ultrasound
images.
PMID- 28692972
TI - Tissue Acoustoelectric Effect Modeling From Solid Mechanics Theory.
AB - The acoustoelectric (AE) effect is a basic physical phenomenon, which underlies
the changes made in the conductivity of a medium by the application of focused
ultrasound. Recently, based on the AE effect, several biomedical imaging
techniques have been widely studied, such as ultrasound-modulated electrical
impedance tomography and ultrasound current source density imaging. To further
investigate the mechanism of the AE effect in tissue and to provide guidance for
such techniques, we have modeled the tissue AE effect using the theory of solid
mechanics. Both bulk compression and thermal expansion of tissue are considered
and discussed. Computation simulation shows that the muscle AE effect result,
conductivity change rate, is 3.26*10-3 with 4.3-MPa peak pressure, satisfying the
theoretical value. Bulk compression plays the main role for muscle AE effect,
while thermal expansion makes almost no contribution to it. In addition, the AE
signals of porcine muscle are measured at different focal positions. With the
same magnitude order and the same change trend, the experiment result confirms
that the simulation result is effective. Both simulation and experimental results
validate that tissue AE effect modeling using solid mechanics theory is feasible,
which is of significance for the further development of related biomedical
imaging techniques.
PMID- 28692973
TI - Greedy Batch-Based Minimum-Cost Flows for Tracking Multiple Objects.
AB - Minimum-cost flow algorithms have recently achieved state-of-the-art results in
multi-object tracking. However, they rely on the whole image sequence as input.
When deployed in real-time applications or in distributed settings, these
algorithms first operate on short batches of frames and then stitch the results
into full trajectories. This decoupled strategy is prone to errors because the
batch-based tracking errors may propagate to the final trajectories and cannot be
corrected by other batches. In this paper, we propose a greedy batch-based
minimum-cost flow approach for tracking multiple objects. Unlike existing
approaches that conduct batch-based tracking and stitching sequentially, we
optimize consecutive batches jointly so that the tracking results on one batch
may benefit the results on the other. Specifically, we apply a generalized
minimum-cost flows (MCF) algorithm on each batch and generate a set of
conflicting trajectories. These trajectories comprise the ones with high
probabilities, but also those with low probabilities potentially missed by
detectors and trackers. We then apply the generalized MCF again to obtain the
optimal matching between trajectories from consecutive batches. Our proposed
approach is simple, effective, and does not require training. We demonstrate the
power of our approach on data sets of different scenarios.
PMID- 28692974
TI - Multi-Image Blind Super-Resolution of 3D Scenes.
AB - We address the problem of estimating the latent high-resolution (HR) image of a
3D scene from a set of non-uniformly motion blurred low-resolution (LR) images
captured in the burst mode using a hand-held camera. Existing blind super
resolution (SR) techniques that account for motion blur are restricted to fronto
parallel planar scenes. We initially develop an SR motion blur model to explain
the image formation process in 3D scenes. We then use this model to solve for the
three unknowns-the camera trajectories, the depth map of the scene, and the
latent HR image. We first compute the global HR camera motion corresponding to
each LR observation from patches lying on a reference depth layer in the input
images. Using the estimated trajectories, we compute the latent HR image and the
underlying depth map iteratively using an alternating minimization framework.
Experiments on synthetic and real data reveal that our proposed method
outperforms the state-of-the-art techniques by a significant margin.
PMID- 28692975
TI - A Novel Method of Minimizing View Synthesis Distortion Based on Its Non
Monotonicity in 3D Video.
AB - In depth-based 3D video, the view synthesis distortion (VSD), is generally
measured by modeling the effect of texture and depth errors separately. With such
a development, it has been referred that the VSD changes monotonically with
respect to to both the texture and depth distortions. In this paper, we find that
the VSD does not always change monotonically with them by both theoretical
analysis and experimental test, when the effect of the texture and depth errors
is considered together. Specifically, first, we prove that the VSD is non
monotonic with the texture distortion. That is, the VSD increases with the
increasing texture distortion at higher distortion range but conversely decreases
with it at lower range. It is different from the general scenario that only
considering the effect of the texture errors. We also analytically depict their
relationship with low computational cost and identify the turning point at which
the change of the VSD is converted. Second, we confirm that the VSD is always
monotonic with the depth distortion, which is consistent with the general
scenario that only considering the effect of the depth errors. The non
monotonicity property of the VSD can be utilized to improve the viewing
performance of 3D video in relevant applications, since a minimal value of the
VSD exists at the turning point. We conduct two applications for this purpose.
First, it is used to generate the synthesis view of minimal distortion, which
achieves 0.51-dB gain of PSNR on average for the tested scenarios. Second, it is
used for lossy compression of texture videos in 3D video, which reduces the
coding rate by 24% on average for the tested scenarios, meanwhile, keeps the VSD
not increased simultaneously.
PMID- 28692976
TI - Near-Infrared Coloring via a Contrast-Preserving Mapping Model.
AB - Near-infrared gray images captured along with corresponding visible color images
have recently proven useful for image restoration and classification. This paper
introduces a new coloring method to add colors to near-infrared gray images based
on a contrast-preserving mapping model. A naive coloring method directly adds the
colors from the visible color image to the near-infrared gray image. However,
this method results in an unrealistic image because of the discrepancies in the
brightness and image structure between the captured near-infrared gray image and
the visible color image. To solve the discrepancy problem, first, we present a
new contrast-preserving mapping model to create a new near-infrared gray image
with a similar appearance in the luminance plane to the visible color image,
while preserving the contrast and details of the captured near-infrared gray
image. Then, we develop a method to derive realistic colors that can be added to
the newly created near-infrared gray image based on the proposed contrast
preserving mapping model. Experimental results show that the proposed new method
not only preserves the local contrast and details of the captured near-infrared
gray image, but also transfers the realistic colors from the visible color image
to the newly created near-infrared gray image. It is also shown that the proposed
near-infrared coloring can be used effectively for noise and haze removal, as
well as local contrast enhancement.
PMID- 28692977
TI - Low-Rank Matrix Completion to Reconstruct Incomplete Rendering Images.
AB - Path tracing provides photo-realistic rendering in many applications but
intermediate previsualization often suffers from distracting noise. Since the
fundamental underlying problem is insufficient samples, we exploit the coherence
of the visual signal to reconstruct missing samples, using a low-rank matrix
completion framework. We present novel methods to construct low rank matrices for
incomplete images including missing pixel, missing sub-pixel, and multi-frame
scenarios. A convolutional neural network provides fast pre-completion for
initialising missing values, and subsequent weighted nuclear norm minimisation
(WNNM) with a parameter adjustment strategy (PAWNNM) efficiently recovers missing
values even in high frequency details. The result shows better visual quality
than recent methods including compressed sensing based reconstruction.
PMID- 28692978
TI - Keshif: Rapid and Expressive Tabular Data Exploration for Novices.
AB - General purpose graphical interfaces for data exploration are typically based on
manual visualization and interaction specifications. While designing manual
specification can be very expressive, it demands high efforts to make effective
decisions, therefore reducing exploratory speed. Instead, principled automated
designs can increase exploratory speed, decrease learning efforts, help avoid
ineffective decisions, and therefore better support data analytics novices.
Towards these goals, we present Keshif, a new systematic design for tabular data
exploration. To summarize a given dataset, Keshif aggregates records by value
within attribute summaries, and visualizes aggregate characteristics using a
consistent design based on data types. To reveal data distribution details,
Keshif features three complementary linked selections: highlighting, filtering,
and comparison. Keshif further increases expressiveness through aggregate
metrics, absolute/part-of scale modes, calculated attributes, and saved
selections, all working in synchrony. Its automated design approach also
simplifies authoring of dashboards composed of summaries and individual records
from raw data using fluid interaction. We show examples selected from datasets
from diverse domains. Our study with novices shows that after exploring raw data
for 15 minutes, our participants reached close to 30 data insights on average,
comparable to other studies with skilled users using more complex tools.
PMID- 28692979
TI - Perceptual Biases in Font Size as a Data Encoding.
AB - Many visualizations, including word clouds, cartographic labels, and word trees,
encode data within the sizes of fonts. While font size can be an intuitive
dimension for the viewer, using it as an encoding can introduce factors that may
bias the perception of the underlying values. Viewers might conflate the size of
a word's font with a word's length, the number of letters it contains, or with
the larger or smaller heights of particular characters ('o' versus 'p' versus
'b'). We present a collection of empirical studies showing that such factors
which are irrelevant to the encoded values-can indeed influence comparative
judgements of font size, though less than conventional wisdom might suggest. We
highlight the largest potential biases, and describe a strategy to mitigate them.
PMID- 28692980
TI - A Control Scheme to Minimize Muscle Energy for Power Assistant Robotic Systems
Under Unknown External Perturbation.
AB - This paper proposes a novel control method to minimize muscle energy for power
assistant robotic systems that support the intended motions of a user under
unknown external perturbations, using surface electromyogram (sEMG) signals.
Conventional control methods based on force/torque (F/T) sensors have limitations
to detect human intentions and could, presumably, misunderstand or distort such
intentions because of external perturbations of the interaction forces, such as
those found in activities of daily living. F/T sensors measure the sum of the
applied force, including unknown external forces and human intention; thus, a
power-assistant robot controller cannot exactly decompose the real human force.
In this paper, we describe a counterexample that cannot be supported by
conventional force-sensor-based control methods. We also verify why these control
methods may guide human behavior in the wrong direction, and thus, have
limitations under unknown external perturbations. We then propose a new control
method to minimize the muscle energy indicated by sEMG signals. The proposed
control approach is fundamentally based on the concept of power-assistance, in
which a robot can reduce the users expended muscle energy while performing given
tasks. The proposed control approach is verified through experiments using a
power-assistant robotic system for the upper limbs under external perturbations.
PMID- 28692981
TI - A New Method to Test the Efficiency of Cochlear Implant Artifacts Removal From
Auditory Evoked Potentials.
AB - Auditory evoked potentials are of great interest to objectively evaluate the
audition in cochlear implant (CI) recipients. However, these measures are impeded
by CI stimulation electrical artifacts present in the EEG. In the first part,
this paper investigates the use of a hybrid model approximating CI patient data.
This model gives access to both uncontaminated and denoised data, thus allowing
for the evaluation of CI artifact removal methods. Here the efficiency of
independent component analysis (ICA) is evaluated in the context of auditory
steady-state responses (ASSRs). A dedicated experimental setup was developed to
simultaneously record EEG data from a normal hearing (NH) participant and CI
artifact data from a phantom equipped with a CI. Hybrid data were obtained as a
linear mixture of both sources. Amplitude-modulated continuous tones were used as
stimuli to elicit ASSRs. After denoising, the comparison of denoised hybrid data
and original NH data showed high correlations between the two datasets,
demonstrating the efficiency of ICA. In the second part, the ICA was applied to
real clinical CI ASSR data. Results support the usefulness of the methodology as
regards the performance evaluation of signal processing methods applied to CI
patient data prior to clinical application.
PMID- 28692982
TI - Multi-Dielectric Brownian Dynamics and Design-Space-Exploration Studies of
Permeation in Ion Channels.
AB - This paper proposes a multi-dielectric Brownian dynamics simulation framework for
design-space-exploration (DSE) studies of ion-channel permeation. The goal of
such DSE studies is to estimate the channel modeling-parameters that minimize the
mean-squared error between the simulated and expected "permeation
characteristics." To address this computational challenge, we use a methodology
based on statistical inference that utilizes the knowledge of channel structure
to prune the design space. We demonstrate the proposed framework and DSE
methodology using a case study based on the KcsA ion channel, in which the design
space is successfully reduced from a 6-D space to a 2-D space. Our results show
that the channel dielectric map computed using the framework matches with that
computed directly using molecular dynamics with an error of 7%. Finally, the
scalability and resolution of the model used are explored, and it is shown that
the memory requirements needed for DSE remain constant as the number of
parameters (degree of heterogeneity) increases.
PMID- 28692983
TI - Robust Principal Component Analysis Regularized by Truncated Nuclear Norm for
Identifying Differentially Expressed Genes.
AB - Identifying differentially expressed genes from the thousands of genes is a
challenging task. Robust principal component analysis (RPCA) is an efficient
method in the identification of differentially expressed genes. RPCA method uses
nuclear norm to approximate the rank function. However, theoretical studies
showed that the nuclear norm minimizes all singular values, so it may not be the
best solution to approximate the rank function. The truncated nuclear norm is
defined as the sum of some smaller singular values, which may achieve a better
approximation of the rank function than nuclear norm. In this paper, a novel
method is proposed by replacing nuclear norm of RPCA with the truncated nuclear
norm, which is named robust principal component analysis regularized by truncated
nuclear norm (TRPCA). The method decomposes the observation matrix of genomic
data into a low-rank matrix and a sparse matrix. Because the significant genes
can be considered as sparse signals, the differentially expressed genes are
viewed as the sparse perturbation signals. Thus, the differentially expressed
genes can be identified according to the sparse matrix. The experimental results
on The Cancer Genome Atlas data illustrate that the TRPCA method outperforms
other state-of-the-art methods in the identification of differentially expressed
genes.
PMID- 28692984
TI - A Study of Cell-free DNA Fragmentation Pattern and Its Application in DNA Sample
Type Classification.
AB - Plasma cell-free DNA (cfDNA) has certain fragmentation patterns, which can bring
non-random base content curves of the sequencing data's beginning cycles. We
studied the patterns and found that we could determine whether a sample is cfDNA
or not by just looking into the first 10 cycles of its base content curves. We
analysed 3189 FastQ files, including 1442 cfDNA, 1234 genomic DNA, 507 FFPE
tumour DNA and 6 urinary cfDNA. By deep analysing these data, we find the
patterns are stable enough to distinguish cfDNA from other kinds of DNA samples.
Based on this finding, we build classification models to recognise cfDNA samples
by their sequencing data. Pattern recognition models are then trained with
different classification algorithms like k-nearest neighbours (KNN), random
forest and support vector machine (SVM). The result of 1000 iteration .632+
bootstrapping shows that all these classifiers can give an average accuracy
higher than 98%, indicating that the cfDNA patterns are unique and can make the
dataset highly separable. The best result is obtained using random forest
classifier with a 99.89% average accuracy (sigma = 0.00068). A tool called
CfdnaPattern (http://github.com/OpenGene/CfdnaPattern) has been developed to
train the model and to predict whether a sample is cfDNA or not.
PMID- 28692985
TI - EmDL: Extracting miRNA-Drug Interactions from Literature.
AB - The microRNAs (miRNAs), regulators of post-transcriptional processes, have been
found to affect the efficacy of drugs by regulating the biological processes in
which the target proteins of drugs may be involved. For example, some drugs
develop resistance when certain miRNAs are overexpressed. Therefore, identifying
miRNAs that affect drug effects can help understand the mechanisms of drug
actions and design more efficient drugs. Although some computational approaches
have been developed to predict miRNA-drug associations, such associations rarely
provide explicit information about which miRNAs and how they affect drug
efficacy. On the other hand, there are rich information about which miRNAs affect
the efficacy of which drugs in the literature. In this paper, we present a novel
text mining approach, named as EmDL (Extracting miRNA-Drug interactions from
Literature), to extract the relationships of miRNAs affecting drug efficacy from
literature. Benchmarking on the drug-miRNA interactions manually extracted from
MEDLINE and PubMed Central, EmDL outperforms traditional text mining approaches
as well as other popular methods for predicting drug-miRNA associations.
Specifically, EmDL can effectively identify the sentences that describe the
relationships of miRNAs affecting drug effects. The drug-miRNA interactome
presented here can help understand how miRNAs affect drug effects and provide
insights into the mechanisms of drug actions. In addition, with the information
about drug-miRNA interactions, more effective drugs or combinatorial strategies
can be designed in the future.The data used here can be accessed at
http://mtd.comp-sysbio.org/.
PMID- 28692986
TI - Heavy-Tailed Noise Suppression and Derivative Wavelet Scalogram for Detecting DNA
Copy Number Aberrations.
AB - Most existing array comparative genomic hybridization (array CGH) data processing
methods and evaluation models assumed that the probability density function (pdf)
of noise in array CGH data is a Gaussian distribution. However, in practice, such
noise distribution is peaky and heavy-tailed. Therefore, a Gaussian pdf is not
adequate to approximate the noise in array CGH data and hence introduces wrong
detections of chromosomal aberrations and leads misunderstanding on disease
pathogenesis. A more accurate and sufficient model of noise in array CGH data is
necessary and beneficial to the detection of DNA copy number variations. We
analyze the real array CGH data from different platforms and show that the
distribution of noise in array CGH data is fitted very well by generalized
Gaussian distribution (GGD). Based on our new noise model, we propose a novel
array CGH processing method combining the advantages of both the smoothing and
segmentation approaches. The new method uses generalized Gaussian bivariate
shrinkage function and one-directional derivative wavelet scalogram in
generalized Gaussian noise. In the smoothing step, with the new generalized
Gaussian noise model, we derive the heavy-tailed noise suppression algorithm in
stationary wavelet domain. In the segmentation step, the 1D Gaussian derivative
wavelet scalogram is employed to detect break points. Both real and simulated
array CGH data with different noises (such as Gaussian noise, GGD noise, and real
noise) are used in our experiments. We demonstrate that our new method
outperforms other state-of-the-art methods, in terms of both root mean squared
errors and receiver operating characteristic curves.
PMID- 28692987
TI - Characterizing and Imaging Gross and Real Finger Contacts under Dynamic Loading.
AB - We describe an instrument intended to study finger contacts under tangential
dynamic loading. This type of loading is relevant to the natural conditions when
touch is used to discriminate and identify the properties of the surfaces of
objects-it is also crucial during object manipulation. The system comprises a
high performance tribometer able to accurately record in vivo the components of
the interfacial forces when a finger interacts with arbitrary surfaces which is
combined with a high-speed, high-definition imaging apparatus. Broadband skin
excitation reproducing the dynamic contact loads previously identified can be
effected while imaging the contact through a transparent window, thus closely
approximating the condition when the skin interacts with a non-transparent
surface during sliding. As a preliminary example of the type of phenomenon that
can be identified with this apparatus, we show that traction in the range from 10
to 1000 Hz tends to decrease faster with excitation frequency for dry fingers
than for moist fingers.
PMID- 28692988
TI - Discriminative Transfer Learning Using Similarities and Dissimilarities.
AB - Transfer learning (TL) aims at solving the problem of learning an effective
classification model for a target category, which has few training samples, by
leveraging knowledge from source categories with far more training data. We
propose a new discriminative TL (DTL) method, combining a series of hypotheses
made by both the model learned with target training samples and the additional
models learned with source category samples. Specifically, we use the sparse
reconstruction residual as a basic discriminant and enhance its discriminative
power by comparing two residuals from a positive and a negative dictionary. On
this basis, we make use of similarities and dissimilarities by choosing both
positively correlated and negatively correlated source categories to form
additional dictionaries. A new Wilcoxon-Mann-Whitney statistic-based cost
function is proposed to choose the additional dictionaries with unbalanced
training data. Also, two parallel boosting processes are applied to both the
positive and negative data distributions to further improve classifier
performance. On two different image classification databases, the proposed DTL
consistently outperforms other state-of-the-art TL methods while at the same time
maintaining very efficient runtime.
PMID- 28692989
TI - An Algorithm for Finding the Most Similar Given Sized Subgraphs in Two Weighted
Graphs.
AB - We propose a weighted common subgraph (WCS) matching algorithm to find the most
similar subgraphs in two labeled weighted graphs. WCS matching, as a natural
generalization of equal-sized graph matching and subgraph matching, has found
wide applications in many computer vision and machine learning tasks. In this
brief, WCS matching is first formulated as a combinatorial optimization problem
over the set of partial permutation matrices. Then, it is approximately solved by
a recently proposed combinatorial optimization framework-graduated nonconvexity
and concavity procedure. Experimental comparisons on both synthetic graphs and
real-world images validate its robustness against noise level, problem size,
outlier number, and edge density.
PMID- 28692990
TI - Discriminative Block-Diagonal Representation Learning for Image Recognition.
AB - Existing block-diagonal representation studies mainly focuses on casting block
diagonal regularization on training data, while only little attention is
dedicated to concurrently learning both block-diagonal representations of
training and test data. In this paper, we propose a discriminative block-diagonal
low-rank representation (BDLRR) method for recognition. In particular, the
elaborate BDLRR is formulated as a joint optimization problem of shrinking the
unfavorable representation from off-block-diagonal elements and strengthening the
compact block-diagonal representation under the semisupervised framework of LRR.
To this end, we first impose penalty constraints on the negative representation
to eliminate the correlation between different classes such that the incoherence
criterion of the extra-class representation is boosted. Moreover, a constructed
subspace model is developed to enhance the self-expressive power of training
samples and further build the representation bridge between the training and test
samples, such that the coherence of the learned intraclass representation is
consistently heightened. Finally, the resulting optimization problem is solved
elegantly by employing an alternative optimization strategy, and a simple
recognition algorithm on the learned representation is utilized for final
prediction. Extensive experimental results demonstrate that the proposed method
achieves superb recognition results on four face image data sets, three character
data sets, and the 15 scene multicategories data set. It not only shows superior
potential on image recognition but also outperforms the state-of-the-art methods.
PMID- 28692991
TI - Bayesian Neighborhood Component Analysis.
AB - Learning a distance metric in feature space potentially improves the performance
of the nearest neighbor classifier and is useful in many real-world applications.
Many metric learning (ML) algorithms are, however, based on the point estimation
of a quadratic optimization problem, which is time-consuming, susceptible to
overfitting, and lacks a natural mechanism to reason with parameter uncertainty-a
property useful especially when the training set is small and/or noisy. To deal
with these issues, we present a novel Bayesian ML (BML) method, called Bayesian
neighborhood component analysis (NCA), based on the well-known NCA method, in
which the metric posterior is characterized by the local label consistency
constraints of observations, encoded with a similarity graph instead of
independent pairwise constraints. For efficient Bayesian inference, we explore
the variational lower bound over the log-likelihood of the original NCA
objective. Experiments on several publicly available data sets demonstrate that
the proposed method is able to learn robust metric measures from small size data
set and/or from challenging training set with labels contaminated by errors. The
proposed method is also shown to outperform a previous pairwise constrained BML
method.
PMID- 28692992
TI - Robustness to Training Disturbances in SpikeProp Learning.
AB - Stability is a key issue during spiking neural network training using SpikeProp.
The inherent nonlinearity of Spiking Neuron means that the learning manifold
changes abruptly; therefore, we need to carefully choose the learning steps at
every instance. Other sources of instability are the external disturbances that
come along with training sample as well as the internal disturbances that arise
due to modeling imperfection. The unstable learning scenario can be indirectly
observed in the form of surges, which are sudden increases in the learning cost
and are a common occurrence during SpikeProp training. Research in the past has
shown that proper learning step size is crucial to minimize surges during
training process. To determine proper learning step in order to avoid steep
learning manifolds, we perform weight convergence analysis of SpikeProp learning
in the presence of disturbance signals. The weight convergence analysis is
further extended to robust stability analysis linked with overall system error.
This ensures boundedness of the total learning error with minimal assumption of
bounded disturbance signals. These analyses result in the learning rate
normalization scheme, which are the key results of this paper. The performance of
learning using this scheme has been compared with the prevailing methods for
different benchmark data sets and the results show that this method has stable
learning reflected by minimal surges during learning, higher success in training
instances, and faster learning as well.
PMID- 28692993
TI - th Moment Exponential Input-to-State Stability of Delayed Recurrent Neural
Networks With Markovian Switching via Vector Lyapunov Function.
AB - In this paper, the th moment input-to-state exponential stability for delayed
recurrent neural networks (DRNNs) with Markovian switching is studied. By using
stochastic analysis techniques and classical Razumikhin techniques, a generalized
vector -operator differential inequality including cross item is obtained.
Without additional restrictive conditions on the time-varying delay, the
sufficient criteria on the th moment input-to-state exponential stability for
DRNNs with Markovian switching are derived by means of the vector -operator
differential inequality. When the input is zero, an improved criterion on
exponential stability is obtained. Two numerical examples are provided to examine
the correctness of the derived results.
PMID- 28692994
TI - Distributed Adaptive Finite-Time Approach for Formation-Containment Control of
Networked Nonlinear Systems Under Directed Topology.
AB - This paper presents a distributed adaptive finite-time control solution to the
formation-containment problem for multiple networked systems with uncertain
nonlinear dynamics and directed communication constraints. By integrating the
special topology feature of the new constructed symmetrical matrix, the technical
difficulty in finite-time formation-containment control arising from the
asymmetrical Laplacian matrix under single-way directed communication is
circumvented. Based upon fractional power feedback of the local error, an
adaptive distributed control scheme is established to drive the leaders into the
prespecified formation configuration in finite time. Meanwhile, a distributed
adaptive control scheme, independent of the unavailable inputs of the leaders, is
designed to keep the followers within a bounded distance from the moving leaders
and then to make the followers enter the convex hull shaped by the formation of
the leaders in finite time. The effectiveness of the proposed control scheme is
confirmed by the simulation.
PMID- 28692995
TI - Size-Scalable Content-Based Histopathological Image Retrieval From Database That
Consists of WSIs.
AB - Content-based image retrieval (CBIR) has been widely researched for
histopathological images. It is challenging to retrieve contently similar regions
from histopathological whole slide images (WSIs) for regions of interest (ROIs)
in different size. In this paper, we propose a novel CBIR framework for database
that consists of WSIs and size-scalable query ROIs. Each WSI in the database is
encoded into a matrix of binary codes. When retrieving, a group of region
proposals that have similar size with the query ROI are firstly located in the
database through an efficient table-lookup approach. Then, these regions are
ranked by a designed multi-binary-code-based similarity measurement. Finally, the
top relevant regions and their locations in the WSIs as well as the corresponding
diagnostic information are returned to assist pathologists. The effectiveness of
the proposed framework is evaluated on a fine-annotated WSI database of
epithelial breast tumors. The experimental results have proved that the proposed
framework is effective for retrieval from database that consists of WSIs.
Specifically, for query ROIs of 4096 4096 pixels, the retrieval precision of the
top 20 return has reached 96% and the retrieval time is less than 1.5 s.
PMID- 28692996
TI - Effectiveness Evaluation of Real-Time Scalp Signal Separating Algorithm on Near
Infrared Spectroscopy Neurofeedback.
AB - Near-infrared spectroscopy (NIRS), one of the candidates to be used in a
neurofeedback system or brain-computer interface (BCI), measures the brain
activity by monitoring the changes in cerebral hemoglobin concentration. However,
hemodynamic changes in the scalp may affect the NIRS signals. In order to remove
the superficial signals when NIRS is used in a neurofeedback system or BCI, real
time processing is necessary. Real-time scalp signal separating (RT-SSS)
algorithm, which is capable of separating the scalp-blood signals from NIRS
signals obtained in real-time, may thus be applied. To demonstrate its
effectiveness, two separate neurofeedback experiments were conducted. In the
first experiment, the feedback signal was the raw NIRS signal recorded while in
the second experiment, deep signal extracted using RT-SSS algorithm was used as
the feedback signal. In both experiments, participants were instructed to control
the feedback signal to follow a predefined track. Accuracy scores were calculated
based on the differences between the trace controlled by feedback signal and the
targeted track. Overall, the second experiment yielded better performance in
terms of accuracy scores. These findings proved that RT-SSS algorithm is
beneficial for neurofeedback.
PMID- 28692997
TI - Automated Classification and Removal of EEG Artifacts With SVM and Wavelet-ICA.
AB - Brain electrical activity recordings by electroencephalography (EEG) are often
contaminated with signal artifacts. Procedures for automated removal of EEG
artifacts are frequently sought for clinical diagnostics and brain-computer
interface applications. In recent years, a combination of independent component
analysis (ICA) and discrete wavelet transform has been introduced as standard
technique for EEG artifact removal. However, in performing the wavelet-ICA
procedure, visual inspection or arbitrary thresholding may be required for
identifying artifactual components in the EEG signal. We now propose a novel
approach for identifying artifactual components separated by wavelet-ICA using a
pretrained support vector machine (SVM). Our method presents a robust and
extendable system that enables fully automated identification and removal of
artifacts from EEG signals, without applying any arbitrary thresholding. Using
test data contaminated by eye blink artifacts, we show that our method performed
better in identifying artifactual components than did existing thresholding
methods. Furthermore, wavelet-ICA in conjunction with SVM successfully removed
target artifacts, while largely retaining the EEG source signals of interest. We
propose a set of features including kurtosis, variance, Shannon's entropy, and
range of amplitude as training and test data of SVM to identify eye blink
artifacts in EEG signals. This combinatorial method is also extendable to
accommodate multiple types of artifacts present in multichannel EEG. We envision
future research to explore other descriptive features corresponding to other
types of artifactual components.
PMID- 28692998
TI - A New Ensemble Classification System For Fracture Zone Prediction Using
Imbalanced Micro-CT Bone Morphometrical Data.
AB - Trabecular bone fractures constitute a major health issue for the modern
societies, with the currently established prediction methods of fracture risk,
such as bone mineral density (BMD), resulting in errors up to 40%. Fracture-zone
prediction based on bone's microstructure has been recently proposed as an
alternative prediction method of fracture risk. In this paper, a classification
system (CS) for the automatic fracture-zone prediction based on an Ensemble of
Imbalanced Learning methods is proposed, following the observation that the
percentage of the actual fractured bone area is significantly smaller than the
intact bone in the case of a fracture event. The sample is divided into Volumes
of Interest (VOIs) of specific size and 29 morphometrical parameters are
calculated from each VOI, which serve as input features for the CS in order for
it to separate the input patterns in to two classes: fractured and nonfractured.
To this end, two well-established Imbalanced Learning methods, namely Random
Undersampling and Synthetic Minority Oversampling, and two popular classification
algorithms, namely Multilayer Perceptrons and Support Vector Machines, are tested
and combined accordingly, to provide the best possible performance on a dataset
that contains 45 specimens' pre- and postfailure scans. The best combination is
then compared with three well-established Ensembles of Imbalanced Learning
methods, namely RUSBoost, UnderBagging and SMOTEBagging. The experimental results
clearly show that the proposed CS outperforms the competition, scoring in some
occasions more than 90% in G-Mean and Area under Curve metrics. Finally, an
investigation on the significance of the various trabecular bone's biomechanical
parameters is made using the sequential forward floating selection technique, in
order to identify possible biomarkers for fracture-zone prediction.
PMID- 28692999
TI - Optic Disk Detection in Fundus Image Based on Structured Learning.
AB - Automated optic disk (OD) detection plays an important role in developing a
computer aided system for eye diseases. In this paper, we propose an algorithm
for the OD detection based on structured learning. A classifier model is trained
based on structured learning. Then, we use the model to achieve the edge map of
OD. Thresholding is performed on the edge map, thus a binary image of the OD is
obtained. Finally, circle Hough transform is carried out to approximate the
boundary of OD by a circle. The proposed algorithm has been evaluated on three
public datasets and obtained promising results. The results (an area overlap and
Dices coefficients of 0.8605 and 0.9181, respectively, an accuracy of 0.9777, and
a true positive and false positive fraction of 0.9183 and 0.0102) show that the
proposed method is very competitive with the state-of-the-art methods and is a
reliable tool for the segmentation of OD.
PMID- 28693000
TI - A New Active Contours Approach for Finger Extensor Tendon Segmentation in
Ultrasound Images Using Prior Knowledge and Phase Symmetry.
AB - This work proposes a new approach for the segmentation of the extensor tendon in
ultrasound images of the second metacarpophalangeal joint (MCPJ). The MCPJ is
known to be frequently involved in early stages of rheumatic diseases like
rheumatoid arthritis. The early detection and follow up of these diseases is
important to start and adapt the treatments properly and, in that way, preventing
irreversible damage of the joints. This work relies on an active contours
framework, preceded by a phase symmetry preprocessing and with prior knowledge
energies, to automatically identify the extensor tendon. Active contours methods
are widely used in ultrasound images because of their robustness to speckle noise
and ability to join unconnected smaller regions into a coherent shape. The tendon
is formulated as a line so open ended active contours were used. Phase symmetry
highlights the tendon, by setting a proper scale range and angle span. The
distance between structures and the tendon slope were also included to enforce
the model based on anatomical characteristics. And finally, the concavity
measures were used because, given the anatomy of the finger, we know that the
tendon line should have less than two concavities. To solve the active contours
energy minimization a genetic algorithm approach was used. Several energy metric
configurations were compared using the modified Hausdorff distance and results
showed that this segmentation is not only possible, but exhibits errors smaller
than 0.5 mm with a confidence of 95% with the phase symmetry preprocessing and
energies based on the line neighborhood, area ratio, slope, and concavity
measurements.
PMID- 28693001
TI - Semi-Supervised Learning Through Label Propagation on Geodesics.
AB - Graph-based semi-supervised learning (SSL) has attracted great attention over the
past decade. However, there are still several open problems in this paper,
including: 1) how to construct an effective graph over data with complex
distribution and 2) how to define and effectively use pair-wise similarity for
robust label propagation. In this paper, we utilize a simple and effective graph
construction method to construct the graph over data lying on multiple data
manifolds. The method can guarantee the connectiveness between pair-wise data
points. Then, the global pair-wise data similarity is naturally characterized by
geodesic distance-based joint probability, where the geodesic distance is
approximated by the graph distance. The new data similarity is much more
effective than previous Euclidean distance-based similarities. To apply data
structure for robust label propagation, Kullback-Leibler divergence is utilized
to measure the inconsistency between the input pair-wise similarity and the
output similarity. In order to further consider intraclass and interclass
variances, a novel regularization term on sample-wise margins is introduced to
the objective function. This enables the proposed method fully utilizes the input
data structure and the label information for classification. An efficient
optimization method and the convergence analysis have been proposed for our
problem. Besides, out-of-sample extension is discussed and addressed. Comparisons
with the state-of-the-art SSL methods on image classification tasks have been
presented to show the effectiveness of the proposed method.
PMID- 28693002
TI - Event-Triggered Communication for Leader-Following Consensus of Second-Order
Multiagent Systems.
AB - This paper is concerned with leader-following consensus of second-order
multiagent systems with nonlinear dynamics. First, to save the limited
communication resources, a new event-triggered control protocol is delicately
developed without requiring continuous communication among the follower agents.
Then, by employing the Lyapunov functional method and the Kronecker product
technique, a novel sufficient criterion with less conservation is derived to
guarantee the leader-following consensus while excluding the Zeno behavior.
Furthermore, for the first time, an algorithm to actively adjust the leader
adjacency matrix is presented, which efficiently expands the application range of
some existing criteria. An example is finally given to illustrate the
effectiveness of theoretical results.
PMID- 28693003
TI - Information-Theoretic Performance Analysis of Sensor Networks via Markov Modeling
of Time Series Data.
AB - This paper presents information-theoretic performance analysis of passive sensor
networks for detection of moving targets. The proposed method falls largely under
the category of data-level information fusion in sensor networks. To this end, a
measure of information contribution for sensors is formulated in a symbolic
dynamics framework. The network information state is approximately represented as
the largest principal component of the time series collected across the network.
To quantify each sensor's contribution for generation of the information content,
Markov machine models as well as x-Markov (pronounced as cross-Markov) machine
models, conditioned on the network information state, are constructed; the
difference between the conditional entropies of these machines is then treated as
an approximate measure of information contribution by the respective sensors. The
x-Markov models represent the conditional temporal statistics given the network
information state. The proposed method has been validated on experimental data
collected from a local area network of passive sensors for target detection,
where the statistical characteristics of environmental disturbances are similar
to those of the target signal in the sense of time scale and texture. A
distinctive feature of the proposed algorithm is that the network decisions are
independent of the behavior and identity of the individual sensors, which is
desirable from computational perspectives. Results are presented to demonstrate
the proposed method's efficacy to correctly identify the presence of a target
with very low false-alarm rates. The performance of the underlying algorithm is
compared with that of a recent data-driven, feature-level information fusion
algorithm. It is shown that the proposed algorithm outperforms the other
algorithm.
PMID- 28693004
TI - Key Frame Extraction in the Summary Space.
AB - Key frame extraction is an efficient way to create the video summary which helps
users obtain a quick comprehension of the video content. Generally, the key
frames should be representative of the video content, meanwhile, diverse to
reduce the redundancy. Based on the assumption that the video data are near a
subspace of a high-dimensional space, a new approach, named as key frame
extraction in the summary space, is proposed for key frame extraction in this
paper. The proposed approach aims to find the representative frames of the video
and filter out similar frames from the representative frame set. First of all,
the video data are mapped to a high-dimensional space, named as summary space.
Then, a new representation is learned for each frame by analyzing the intrinsic
structure of the summary space. Specifically, the learned representation can
reflect the representativeness of the frame, and is utilized to select
representative frames. Next, the perceptual hash algorithm is employed to measure
the similarity of representative frames. As a result, the key frame set is
obtained after filtering out similar frames from the representative frame set.
Finally, the video summary is constructed by assigning the key frames in temporal
order. Additionally, the ground truth, created by filtering out similar frames
from human-created summaries, is utilized to evaluate the quality of the video
summary. Compared with several traditional approaches, the experimental results
on 80 videos from two datasets indicate the superior performance of our approach.
PMID- 28693005
TI - George Papanicolaou's Efforts to Develop Novel Cytologic Methods for the Early
Diagnosis of Endometrial Carcinoma.
AB - Toward the end of his career, Dr. George Papanicolaou became interested in human
endometrial explants placed into tissue culture. The initial focus of his studies
was on phagocytic cells emanating from endometrial explants and their role in
cleansing the uterine cavity after each menstrual cycle and in sterilizing the
uterine cavity in the face of infection. Papanicolaou also observed that growth
rates of explanted normal and pathologic endometrial tissues differed
considerably. Explants of endometrial malignancies exhibited not only increased
growth rates but also visible proliferation of cells with readily identifiable
cytologic features of malignancy. Acknowledging that cytologic screening for
early diagnosis of intrauterine malignancies had up to that point not proven to
be reliable as screening for cervical cancer, he hoped that the tissue culture
explant technique could prove to be a new adjunctive diagnostic method for the
diagnosis of endometrial and other female genital tract malignancies not readily
detectible by other diagnostic procedures. Papanicolaou's untimely death in 1962
cut short his progress in this area of study.
PMID- 28693006
TI - Two Fortuitous Papers in 1917 That Conceived Diagnostic Cytopathology.
PMID- 28693007
TI - Dr. Bibbo's Presidential Address on Automation in Cytology: Were Her Predictions
Right, Wrong, or Somewhere in the Middle?
AB - In 1983, Dr. Marluce Bibbo gave the Presidential Address at the Annual Meeting of
the American Society of Cytology in Denver, CO, USA. The lecture was entitled
"Analytic and Quantitative Cytology," a field in which Dr. Bibbo was intimately
involved. In the presentation, she included a summary of 30 years of work already
accomplished, the present state of the art, and musings about issues encountered,
potential resolutions, progress that needed to be made, and her perception of how
the field needed to evolve in order to become ultimately successful as a clinical
service. This commentary looks back 34 years, with observations about Dr. Bibbo's
predictions and how the field of cytology automation did actually evolve in the
decades following her address. New challenges are identified and possible paths
forward are discussed.
PMID- 28693008
TI - Two Landmark Studies Published in 1976/1977 Paved the Way for the Recognition of
Human Papillomavirus as the Major Cause of the Global Cancer Burden.
AB - Two groundbreaking reports were published in Acta Cytologica at the transition of
1976 to 1977. One appeared in the last issue of 1976 [Meisels and Fortin: Acta
Cytol 1976;20:505-509] and the other in the first issue of 1977 [Purola and
Savia: Acta Cytol 1977;21:26-31]. Today, 40 years later, it is not an
overstatement to conclude that these are the two most influential studies ever
published in this journal. Two reports with a similar content being published so
close together (in the same journal) raised the question "Which of the two
reports was truly submitted first?" In this commentary, this enigma is clarified
beyond reasonable doubt, based on the well-considered testimonial of Prof.
Leopold G. Koss, the reviewer of one of the two papers. To fully appreciate the
significance of the novel discovery made in these two reports, it is essential to
align them in the right context, both retrospectively and prospectively. This
commentary will assist the reader by summarizing the existing knowledge on human
papillomavirus (HPV) before these two milestone papers appeared, and describe the
incredibly rapid progress that they evoked during the subsequent decades, which
made HPV the single most important human tumor virus. As the final proof of virus
cancer causality, prophylactic HPV vaccines have been effective in preventing (a)
virus transmission and HPV infection, (b) benign HPV-induced tumors (genital
warts), and (c) cervical intraepithelial neoplasia (CIN). Formal evidence of the
prevention of cervical cancer by these HPV vaccines still awaits confirmation,
and the same applies to the eventual prevention of human cancers at other
anatomic sites, part of the global burden of oncogenic HPVs.
PMID- 28693009
TI - A Review of the Use of Fine-Needle Aspiration Biopsy of Mammary Tumors for
Diagnosis and Research.
AB - The article "Aspiration Biopsy of Mammary Tumors in Diagnosis and Research - A
Critical Review of 2,200 Cases" by Zajicek et al. [Acta Cytol 1967;11:169-175] is
composed of two separate parts as can be seen from the title. Both are, however,
of great historical interest. The first describes the early days of fine-needle
aspiration cytology diagnosis of breast lesions in particular carcinomas. The
results are still impressive with a diagnostic accuracy close to 90%. The second
deals with the effect of negative pressure on cell viability during the
aspiration procedure. These studies were aimed at evaluating the usefulness of
aspirated tumor cells to analyze the effects of therapy and the origin of tumor
cells.
PMID- 28693010
TI - The Six Decades of Acta Cytologica.
PMID- 28693011
TI - Comparacion de la efectividad de ranibizumab intravitreo para el tratamiento del
edema macular diabetico en ojos vitrectomizados y no vitrectomizados.
AB - Objetivo: Comparar la efectividad de ranibizumab intravitreo (RIV) para el
tratamiento del edema macular diabetico (EMD) en ojos con y sin vitrectomia
previa. Procedimientos: Evaluamos de manera prospectiva la mejor agudeza visual
corregida (MAVC) y el grosor macular central (GMC) tras el tratamiento con RIV
durante 6 meses. Resultados: No se observaron diferencias significativas en la
MAVC o GMC inicial en ninguno de los dos grupos. En el grupo no vitrectomizado (n
= 15), los cambios medios en la MAVC y GMC hasta el sexto mes de tratamiento con
respecto al valor inicial resultaron significativos (p < 0,01). En el grupo
vitrectomizado (n = 10), se observo una mejora mas lenta, y la mejora media en la
MAVC no resulto significativa (p = 0,5), aunque la media en la disminucion del
GMC si que lo fue (p < 0,05). No se observaron diferencias significativas en los
cambios medios en la MAVC y el GMC entre ambos grupos a los 6 meses del
tratamiento. Conclusiones: La diferencia en la efectividad de RIV entre ambos
grupos no resulto significativa. Ranibizumab intravitreo puede ser una opcion de
tratamiento incluso en pacientes vitrectomizados con EMD.
PMID- 28693012
TI - Stress Measured by Allostatic Load in Neurologically Impaired Children: The
Importance of Nutritional Status.
AB - BACKGROUND: Allostatic load (AL) is the cumulative physiological wear and tear
that results from repeated efforts to adapt to stressors over time. The life
stress response is modified by nutritional status. AIM: We estimated AL scores
among neurologically impaired (NI) children; the association with malnutrition
was also evaluated. METHODS: Forty-one patients with severe disabilities were
included. Data based on 15 biomarkers were used to create the AL score. A
dichotomous outcome of high AL was defined for those who had >=6 dysregulated
components. Body mass index (BMI)-standard deviation score (SDS) <-2 or SDS >=2
and biochemical markers (>=4) defined malnutrition. RESULTS: High AL was noted in
17/41 of the whole sample (41.47%). Malnutrition occurred in 36.6% of the
subjects. A significant correlation between high AL and malnutrition was observed
(p = 0.01; ar ea under the receiver operating characteristic curve, 0.7457). High
AL subjects had a significantly higher BMI (p = 0.009) and lower BMI-SDS (p =
0.003) than low AL subjects. AL score correlated with fat mass (p <= 0.01) and
negatively correlated with fat-free mass (p <= 0.02). CONCLUSION: In NI children,
high AL was associated with malnutrition. Body composition is a better indicator
than BMI of allostatic adjustments. AL estimation should be considered a measure
of health risk and be used to promote quality of life in at-risk disabled
populations.
PMID- 28693013
TI - Circulating Tumor Cells in Esophageal Cancer.
AB - Esophageal cancer (EC) is mostly diagnosed due to clinical symptoms such as
dysphagia or anemia. Depending on the staging and the histological subtype,
squamous cell carcinoma or adenocarcinoma, patients with non-metastasized disease
mostly undergo neoadjuvant chemoradiation or perioperative chemotherapy followed
by esophageal resection. Nearly 50% of the curatively treated patients develop
distant metastasis within 5 years, although no metastases were clinically evident
at time of treatment. More recently, the concept of circulating tumor cells (CTC)
has also been introduced for EC. CTC are thought to be the means of systemic
tumor spread, with the ability to set up metastases in distant organs. Much
effort has been made to capture, enrich and detect these very rare cells from the
blood stream of EC patients. CTC have been found to be independent risk factors
for worse prognosis in patients with EC. Pre- and intra-therapeutic CTC
enrichment and detection has the potential to improve preoperative staging, and
provide a differential indication for neoadjuvant therapeutic modality and an
indication for adjuvant therapy.
PMID- 28693014
TI - A Groundbreaking Work Which Laid the Foundation for Mass Screening in Cervical
Cytology in Japan.
AB - This commentary discusses the impact of a milestone article on the accuracy of
cervical smears for detecting cancer back in the developmental and transforming
era of the cytological detection of atypical and malignant cells. The study
served in the establishment of cancer screening in Japan which has contributed
greatly in decreasing mortality from cervical cancers.
PMID- 28693015
TI - Criticism of the Pap Smear as a Diagnostic Tool in Cervical Cancer Screening.
AB - This editorial by Dr. Leopold G. Koss appeared in the January 1980 issue of Acta
Cytologica. It addressed recent critical opinions in the general media on
cervical screening and its costs. It marked the beginning of a more critical
approach to cytology by the lay press, health care providers, and
epidemiologists. It was also the first of a series of highly informative
editorials by Dr. Koss that illustrated the critical issues of cytology during
the 1980s. The elegance and clarity of his articles reflect the high standard of
editorial writing in Acta Cytologica at this time. These articles are reviewed
and excerpts are presented.
PMID- 28693016
TI - Cranioplasty without Periosteal Dissection Reduces Blood Loss in Pi-Plasty
Surgery for Sagittal Synostosis.
AB - BACKGROUND/AIMS: Cranioplasty is often accompanied by a substantial oozing
bleeding from the bone surface and bone edges. Our aim was to measure if strict
subgaleal dissection without any periosteal release reduces blood loss during pi
plasty surgery for sagittal synostosis. METHOD: A group of 32 children who
underwent pi-plasty surgery at the Sahlgrenska University Hospital between 2010
and 2014 for premature sagittal synostosis with traditional subgaleal dissection
combined with incision and release of the periosteum adjacent to the osteotomy
lines was compared to a group of 7 children who underwent pi-plasty with strict
subgaleal dissection and osteotomy through the bone with the periosteum attached.
Information about blood loss and body weight was extracted from medical records.
RESULTS: The blood loss in the group of 7 children with strict subgaleal
dissection was 102 +/- 86 mL (mean +/- SD) (10 +/- 7 mL/kg) compared to 320 +/-
119 mL (32 +/- 12 mL/kg) in the control group with traditional periosteal release
(p < 0.001). CONCLUSION: Intact periosteum at the osteotomy lines significantly
reduces blood loss in pi-plasty surgery for sagittal synostosis. The mechanism is
likely because of preserved veins between the bone surface and periosteum.
PMID- 28693017
TI - The Bethesda System for Reporting Cervical Cytology: A Historical Perspective.
AB - The aims of The Bethesda System (TBS) were to provide effective communication
from the laboratory to the clinical provider; facilitate cytologic-histologic
correlation; facilitate research into the epidemiology, biology, and pathology of
cervical disease; and provide reproducible and reliable data for national and
international statistical analysis comparisons. Dr. Diane Solomon and colleagues'
contribution to cervical cancer screening, diagnosis, and management began with
the inception and dissemination of TBS for reporting cervical cytology in 1988,
as detailed in the accompanying article [Solomon et al.: Acta Cytol 1989;33:567
574]. The significance of TBS for the further development and implementation of
standardized terminology in pathology, and the research/management of cervical
cancer have continued to evolve over the past three decades. TBS has always been
a multidisciplinary effort and acknowledgement needs to be given to several
stakeholders who, over the years, have contributed to its success. It has been
our privilege and honor to have carried on the legacy of this seminal work, even
as molecular methods are being closely integrated into cervical cancer screening,
triage, and prevention.
PMID- 28693018
TI - El efecto de la panfotocoagulacion con laser en edema macular diabetico con el
fotocoagulador Pascal(r) versus el laser de argon convencional.
AB - Objetivo: El objetivo de este estudio fue comparar el efecto de la
panfotocoagulacion (PFC) en el edema macular diabetico (EMD) en pacientes con
retinopatia diabetica proliferativa (RDP) con el fotocoagulador Pascal(r) (FP)
vs. un fotocoagulador con laser de argon convencional (FLAC). Metodos: Se
aleatorizo el uso de FP o FLAC en ochenta ojos con RDP y EMD con afectacion
central de la macula. Ambos grupos tuvieron una evaluacion de base de mejor
agudeza visual corregida y fueron examinados con tomografia de coherencia optica
y angiografia con fluoresceina. Resultados: El numero medio de disparos de laser
en los grupos de FP y FLAC fue 1.726,10 y 752,00 en la sesion 1 y 1.589,00 y
830,00 (p < 0,001) en la sesion 2, respectivamente. El grosor foveal central
(GFC) medio antes de comenzar el estudio fue 306 +/- 100 y 314 +/- 98 en los
grupos de FP y FLAC, respectivamente. A las 8 semanas, el GFC medio fue 332 +/-
116 y 347 +/- 111 en los grupos de FP y FLAC, respectivamente (p > 0,05). La MAVC
media fue similar durante el periodo de estudio y no hubo ninguna diferencia
significativa entre los grupos (p > 0,05). Conclusiones: El FP y el FLAC
mostraron efectos similares en el EMD en ojos con RDP y fueron igualmente seguros
sin un aumento significativo del GFC.
PMID- 28693020
TI - Propiedades biomecanicas de la membrana limitante interna tras recibir
tratamiento intravitreo con ocriplasmina.
AB - Objetivo: Evaluar la rigidez de la membrana limitante interna (MLI) humana y
evaluar los posibles cambios de las propiedades mecanicas tras administrar una
inyeccion intravitrea de ocriplasmina para tratar la traccion vitreomacular.
Metodos: Este estudio se compone de una serie de casos intervencionales y
comparativos de 12 muestras de MLI extraidas mediante cirugia y obtenidas de
forma consecutiva de 9 ojos de 9 pacientes despues de someterse sin exito a
vitreolisis farmacologica con ocriplasmina. Durante el mismo periodo de tiempo,
16 muestras de otros 13 ojos sin tratamiento con ocriplasmina se obtuvieron
mediante vitrectomia y sirvieron como controles. Todos los pacientes presentaron
agujeros maculares o traccion vitreomacular y se sometieron a vitrectomia con
diseccion de la MLI tanto con tincion con azul brillante (AB) como sin ella.
Todas las muestras se analizaron con un microscopio de fuerza atomica con
imagenes de las regiones de 25 * 25 MUm. En todas las muestras, se analizaron
tanto la parte de la retina como la del vitreo de la MLI. Resultados: La
microscopia de fuerza atomica no revelo diferencias significativas en cuanto a
elasticidad de las muestras de MLI extraidas de ojos con o sin tratamiento con
ocriplasmina. Las areas onduladas de la parte de la retina presentaron una mayor
rigidez que la parte del vitreo de la MLI. La cartografia topografica tanto de la
parte del vitreo como de la retina de la MLI no mostro ninguna alteracion
aparente de la morfologia en ojos tratados con ocriplasmina en comparacion con
los ojos no tratados. La tincion con azul brillante conllevo un aumento de la
rigidez tisular. Conclusiones: Las inyecciones intravitreas de ocriplasmina no
varian las propiedades biomecanicas de la MLI humana. No existen pruebas de un
posible efecto enzimatico que interfiera con la rigidez de esta membrana basal.
PMID- 28693021
TI - Sobre la terapia genica para enfermedades de la retina.
AB - Las mutaciones en un gran numero de genes provocan degeneracion de la retina y
ceguera sin que exista actualmente cura alguna. En las ultimas decadas, la
terapia genica para enfermedades de la retina ha evolucionado y se ha convertido
en un nuevo y prometedor paradigma terapeutico para estas enfermedades poco
comunes. Este articulo refleja las ideas y los conceptos que parten de la ciencia
basica hacia la aplicabilidad de la terapia genica en el ambito clinico. Se
describen los avances y las reflexiones actuales sobre la eficacia de los ensayos
clinicos en la actualidad y se discuten los posibles obstaculos y soluciones de
cara al futuro de la terapia genica para enfermedades de la retina.
PMID- 28693022
TI - Temsirolimus Sensitive Stimulation of Platelet Activity, Apoptosis and
Aggregation by Collagen Related Peptide.
AB - BACKGROUND/AIMS: The mammalian target of rapamycin (mTOR) inhibitor temsirolimus
stimulates apoptosis of tumor cells and is thus therapeutically used for the
treatment of diverse malignancies. On the other hand, temsirolimus has been shown
to protect against apoptosis of hippocampal neurons. Similar to nucleated cells,
blood platelets may enter suicidal death characterized by cell shrinkage and cell
membrane scrambling. Platelet apoptosis is frequently preceded by Ca2+ entry,
degranulation, integrin activation and stimulation of caspases. Those events
could be triggered by collagen related peptide (CRP). The present study explored
whether treatment of platelets with temsirolimus modifies platelet activation,
caspase activity, platelet shrinkage, and phosphatidylserine abundance. METHODS:
Platelets isolated from wild-type mice were exposed for 30 minutes to
temsirolimus (40 ug/ml) without or with additional CRP (2 ug/ ml or 5 ug/ml)
treatment. Flow cytometry was employed to estimate cytosolic Ca2+-activity
([Ca2+]i) from Fluo-3 fuorescence, platelet degranulation from P-selectin
abundance, integrin activation from alphaIIbbeta3 integrin abundance, caspase
activity utilizing an Active Caspase-3 Staining kit, phosphatidylserine abundance
from annexin-V-binding and relative platelet volume from forward scatter.
RESULTS: In the absence of CRP, the administration of temsirolimus (40 ug/ml)
significantly decreased [Ca2+]i, but did not significantly modify P-selectin
abundance, activated alphaIIbbeta3 integrin, annexin-V-binding, cell volume,
caspase activity and aggregation. Exposure of platelets to CRP was followed by
significant increase of [Ca2+]i, P-selectin abundance, alphaIIbbeta3 integrin
activity, annexin-V-binding, ROS, caspase activity and aggregation, effects
significantly blunted in the presence of temsirolimus. CRP further decreased
forward scatter, an effect again significantly blunted by temsirolimus.
CONCLUSIONS: Temsirolimus is a powerful inhibitor of platelet activation and
suicidal platelet death.
PMID- 28693023
TI - Liquid Biopsy: Current Status and Future Perspectives.
AB - Cancer patients usually receive therapies according to their primary tumor's
molecular traits. These characteristics may change during the molecular evolution
of distant metastases as the leading cause of cancer deaths. Primary tumor
tissue, if accessible at all, does not always provide enough information to
stratify individual patients to the most promising therapy. Re-analysis of
metastatic lesions by needle biopsy is possible but invasive, and limited by the
known intra-patient heterogeneity of individual lesions. These hurdles might be
overcome by analyzing tumor cells or tumor cell products in blood samples (liquid
biopsy), which in principle might reflect all subclones present at that specific
time point and allow sequential monitoring of disease evolution. Liquid biopsies
inform on circulating tumor cells as well as tumor-derived cell-free nucleic
acids, exosomes and platelets. Here, we introduce the different approaches of
blood-based liquid biopsies and discuss the clinical applications in oncology.
PMID- 28693024
TI - International Symposium on Immunonutrition 2017, Madrid, 17th-19th July, 2017,
10th Anniversary: Abstracts.
PMID- 28693026
TI - Liquid Biopsy: Approaches to Dynamic Genotyping in Cancer.
AB - Malignant tumors release tumor cells and fragments of nucleic acids into the
bloodstream. Liquid biopsies are non-invasive blood tests that detect circulating
tumor cells (CTC) and circulating nucleic acids such as mRNA, microRNA, and cell
free circulating tumor DNA, also known as ctDNA. The presence of ctDNA or CTCs in
the plasma has prognostic impact. Since ctDNA contains tumor-specific mutations,
its detection in the blood or other body fluids can predict response to treatment
and relapse. Moreover, repeated analysis and quantitation of ctDNA can inform
about changes in clonal composition over time and thus allow dynamic treatment
stratification. Today, the routine clinical use of liquid biopsy diagnostic tests
is limited; however, in the near future, they might become commonly used
sensitive and specific biomarkers to guide cancer treatment. This review will
summarize recent findings on the use of ctDNA for monitoring response to therapy
and dynamic genetic treatment stratification.
PMID- 28693025
TI - Infusion of Valproic Acid Into the Renal Medulla Activates Stem Cell Population
and Attenuates Salt-Sensitive Hypertension in Dahl S Rats.
AB - BACKGROUND: Our previous study has detected a stem cell deficiency in the renal
medulla in Dahl salt-sensitive (S) rats. This study determined whether infusion
of valproic acid (VA), an agent known to stimulate the stem cell function,
attenuated salt-sensitive hypertension in Dahl S rats. METHODS: Uninephrectomized
Dahl S rats were infused with vehicle or VA (50mg/kg/d) into the renal medulla
and fed with a low (LS) or high salt diet (HS). Stem cell marker and number were
analyzed by immunohistochemistry, Real-time RT-PCR and Western blot. Sodium
excretion and blood pressure were measured. RESULTS: VA significantly increased
the mRNA and protein levels of FGF2, a stem cell niche factor, and CD133, a stem
cell marker. The number of CD133+ cells was significantly increased in the renal
medulla in VA-treated rats. Meanwhile, high salt-induced increases in the mRNA
level of proinflammatory factors interleukin-1beta and interleukin-6 were blocked
in VA-treated rats. Functionally, sodium excretion in response to the blood
pressure increase and acute sodium loading was significantly enhanced, sodium
retention attenuated, high salt-induced increase of blood pressure reduced in VA
treated rats. CONCLUSION: Activation of stem cell function by VA inhibits the
activation of proinflammatory factors and attenuates salt-sensitive hypertension
in Dahl S rats.
PMID- 28693027
TI - Expectations and Projections for the Future of Nongynecolgical Cytology 10 Years
Ago: Did They Materialize and How Did We Do?
AB - In 2007, an article entitled "How Technology Is Reshaping the Practice of
Nongynecologic Cytology: Frontiers of Cytology Symposium" [Bibbo: Acta Cytol
2007;51:123-152] was published. The moderator and editor was Marluce Bibbo,
previous Editor-in-Chief of Acta Cytologica, and 17 participants from countries
throughout the world were asked to answer how new technologies were being applied
in their respective laboratories and whether future advances and challenges can
be predicted. Ten years later, two previous participants in this Golden
Anniversary Cytology Symposium were asked by Kari Syrjanen, current Editor-in
Chief of Acta Cytologica, to make a reappraisal of the 2007 predictions.
PMID- 28693028
TI - Desgarros del epitelio pigmentario de la retina: factores de riesgo, mecanismo y
control terapeutico.
AB - Los desgarros del epitelio pigmentario de la retina (EPR) se asocian en la
mayoria de los casos con los desprendimientos vascularizados del EPR debido a una
degeneracion macular asociada a la edad (DMAE), y normalmente implican una
perdida adversa de la agudeza visual. Estudios recientes indican que ha habido un
aumento en la incidencia de desgarros del EPR desde la introduccion de farmacos
anti-factor de crecimiento del endotelio vascular (anti-VEGF) asi como una
asociacion temporal entre el desgarro y la inyeccion intravitrea. Dado que el
numero de pacientes con DMAE y el numero de inyecciones anti-VEGF va en aumento,
tanto la dificultad de prevenir desgarros del EPR como el tratamiento tras la
formacion de los desgarros han adquirido una mayor relevancia. De forma paralela,
la evolucion de la imagenologia de la retina ha contribuido de manera
significativa a comprender mejor el desarrollo de los desgarros del EPR en los
ultimos anos. Esta revision resume los conocimientos que se poseen actualmente
sobre el desarrollo, los factores pronosticos y las estrategias terapeuticas de
los desgarros del EPR antes y despues de que estos se formen.
PMID- 28693029
TI - Angio-OCT de la zona avascular foveal en ojos con oclusion venosa de la retina.
AB - Objetivo: El objetivo del estudio comprendia visualizar y cuantificar las
alteraciones patologicas de la zona avascular foveal (ZAF) mediante angio-OCT en
ojos con oclusion venosa de la retina (OVR) en comparacion con el ojo
contralateral sano. Procedimientos: La angio-OCT se llevo a cabo mediante el
sistema Avanti(r) RTVue 100 XR (Optovue Inc., Fremont, Calif., EE. UU.). Los
bordes de la capa vascular superficial (CVS) se definieron como 3 MUm por debajo
de la membrana limitante interna y 15 MUm por debajo de la capa plexiforme
interna y, para la capa vascular profunda (CVP), como 15 y 70 MUm por debajo de
la membrana limitante interna y de la capa plexiforme interna, respectivamente.
La longitud de la ZAF horizontal, vertical y maxima de la CVS y la CVP en cada
ojo se midio de forma manual. Ademas, se midio el angulo entre el diametro maximo
de la ZAF y el plano papilomacular. Resultados: La angio-OCT represento los
defectos dentro de la vasculatura en el area perifoveal en ojos con oclusion de
rama venosa de la retina (ORVR; n = 11) y con oclusion de la vena central de la
retina (OVCR; n = 8). Esto resulto en un crecimiento del diametro maximo de la
ZAF en ojos con OVR (n = 19) en comparacion con el ojo contralateral (n = 19; 921
+/- 213 frente a 724 +/- 145 um; p = 0,008). Ademas, se observo una correlacion
significativa entre la mejor agudeza visual corregida (MAVC) y el diametro maximo
de la ZAF en la CVP (rho de Spearman = -0,423, p < 0,01). Por ultimo, en los ojos
con OVR, el angulo entre el plano papilomacular y el diametro maximo de la ZAF se
dio tan solo en el 21,05% (CVS) y en el 15,79% (CVP) de los casos a 0 +/- 15 o 90
+/- 15 degrees , respectivamente. En ojos sanos, estos angulos (que supuestamente
representan una configuracion de la ZAF regular) fueron mas prevalentes (CVS
68,42 frente a 21,05%, p = 0,003; CVP 73,68 frente a 15,79%, p < 0,001).
Conclusiones: La angio-OCT muestra alteraciones morfologicas de la ZAF en ojos
con OVCR y ORVR. La correlacion del diametro maximo de la ZAF con la MAVC indica
que estas alteraciones resultan funcionalmente relevantes.
PMID- 28693030
TI - Prevalencia de alteraciones en la interfase vitreoretiniana detectadas mediante
tomografia de coherencia optica de dominio espectral.
AB - Objetivo: El objetivo principal del presente estudio consistio en determinar la
prevalencia de los cambios en la interfase vitreomacular (IVM) mediante
tomografia de coherencia optica (OCT) en la poblacion general. En segundo lugar,
se describieron otros cambios de la OCT. Metodos: Las anomalias en la IVM se
diagnosticaron mediante OCT y se distribuyeron de acuerdo con la clasificacion
del grupo International Vitreomacular Traction Study (estudio internacional de
traccion vitreomacular, IVTS, por sus siglas en ingles) y se dividieron en 3
grados segun John et al. [Retina 2014;34:442-446]. Resultados: La prevalencia
calculada de anomalias vitreomaculares en la poblacion belga de >=50 anos fue del
1,17% [intervalo de confianza (IC 0,38-3,62)] en el caso de traccion
vitreomacular (TVM) focal de grado 1; del 0,39% (IC 0,05-2,76) en el caso de TVM
focal de grado 2; del 8,17% (IC 5,33-12,53) en el caso de adhesion vitreomacular
focal; y del 17,9% (IC 13,41-23,9) en el caso de adhesion vitreomacular difusa.
Conclusiones: Se presento la prevalencia de anomalias vitreomaculares en un
estudio de cohortes belga. Estos resultados concuerdan en gran medida con los
datos presentados previamente sobre la prevalencia de la TVM. Un conocimiento
correcto sobre la epidemiologia de las alteraciones en la IVM y un diagnostico
temprano permitiran una intervencion satisfactoria.
PMID- 28693032
TI - Acta Reumatologica Portuguesa: perspectives in 2017.
PMID- 28693033
TI - Axial involvement according to ASAS criteria in an observational psoriatic
arthritis cohort.
AB - The definition of axial involvement in psoriatic arthritis (PsA) is still under
debate. Currently, the axial spondyloarthritis (SpA) criteria defined by
Assessment of Spondyloarthritis International Society (ASAS) may be the most
adequate.(1) The aims of present study were to assess axial involvement according
to ASAS criteria in an observational PsA cohort and define the clinical
characteristics more associated with this kind of involvement. Our study included
consecutive patients who had a visit in a tertiary Rheumatology centre. All
patients included fulfill ClASsification criteria for Psoriatic Arthritis
(CASPAR) criteria for PsA and all of them had a recent radiographic assessment of
sacroiliitis. Clinical and laboratorial data were taken into account to classify
patients as fulfilling or not ASAS criteria for axial SpA. Clinical and
demographic data were analyzed about their association with presence of ASAS
criteria of axial SpA in an univariable logistic regression analysis. Variables
with a p-value <0.05 were re-tested in a multivariable logistic regression. Those
variables that maintained statistical significance were tested alone in another
multivariable model. Analyses were performed with IBM SPSS Statistics (version
20.0). Regarding the 233 patients included, only 42 patients (19.4%) fulfilled
ASAS criteria for axial SpA. However, 22 patients had asymptomatic radiographic
sacroiliitis according to modified New York criteria. The prevalence of
asymptomatic sacroiliitis was 15.7% between patients without axial symptoms. In
multivariable analysis, inflammatory back pain (IBP) [OR=25.111; 95% confidence
interval (CI) = 8.770, 71.900, p-value <0.001], presence of HLA-B27 [OR=9.072;
95% CI=2.756, 29.860; p-value <0.001] and male gender [OR=3.767; 95% CI=1.264,
11.232; p-value = 0.017] were associated to axial involvement according to ASAS
criteria. Axial SpA ASAS criteria are useful to identify axial involvement in PsA
patients. This type of involvement is more common in males, in the presence of
HLA-B27 and IBP. Axial disease should be systematically assessed in clinical
practice, mainly in patients presenting with this clinical features.
PMID- 28693034
TI - Large-scale physical activity data reveal worldwide activity inequality.
AB - To be able to curb the global pandemic of physical inactivity and the associated
5.3 million deaths per year, we need to understand the basic principles that
govern physical activity. However, there is a lack of large-scale measurements of
physical activity patterns across free-living populations worldwide. Here we
leverage the wide usage of smartphones with built-in accelerometry to measure
physical activity at the global scale. We study a dataset consisting of 68
million days of physical activity for 717,527 people, giving us a window into
activity in 111 countries across the globe. We find inequality in how activity is
distributed within countries and that this inequality is a better predictor of
obesity prevalence in the population than average activity volume. Reduced
activity in females contributes to a large portion of the observed activity
inequality. Aspects of the built environment, such as the walkability of a city,
are associated with a smaller gender gap in activity and lower activity
inequality. In more walkable cities, activity is greater throughout the day and
throughout the week, across age, gender, and body mass index (BMI) groups, with
the greatest increases in activity found for females. Our findings have
implications for global public health policy and urban planning and highlight the
role of activity inequality and the built environment in improving physical
activity and health.
PMID- 28693036
TI - Association of Coffee Consumption With Total and Cause-Specific Mortality Among
Nonwhite Populations.
AB - Background: Coffee consumption has been associated with reduced risk for death in
prospective cohort studies; however, data in nonwhites are sparse. Objective: To
examine the association of coffee consumption with risk for total and cause
specific death. Design: The MEC (Multiethnic Cohort), a prospective population
based cohort study established between 1993 and 1996. Setting: Hawaii and Los
Angeles, California. Participants: 185 855 African Americans, Native Hawaiians,
Japanese Americans, Latinos, and whites aged 45 to 75 years at recruitment.
Measurements: Outcomes were total and cause-specific mortality between 1993 and
2012. Coffee intake was assessed at baseline by means of a validated food
frequency questionnaire. Results: 58 397 participants died during 3 195 484
person-years of follow-up (average follow-up, 16.2 years). Compared with drinking
no coffee, coffee consumption was associated with lower total mortality after
adjustment for smoking and other potential confounders (1 cup per day: hazard
ratio [HR], 0.88 [95% CI, 0.85 to 0.91]; 2 to 3 cups per day: HR, 0.82 [CI, 0.79
to 0.86]; >=4 cups per day: HR, 0.82 [CI, 0.78 to 0.87]; P for trend < 0.001).
Trends were similar between caffeinated and decaffeinated coffee. Significant
inverse associations were observed in 4 ethnic groups; the association in Native
Hawaiians did not reach statistical significance. Inverse associations were also
seen in never-smokers, younger participants (<55 years), and those who had not
previously reported a chronic disease. Among examined end points, inverse
associations were observed for deaths due to heart disease, cancer, respiratory
disease, stroke, diabetes, and kidney disease. Limitation: Unmeasured confounding
and measurement error, although sensitivity analysis suggested that neither was
likely to affect results. Conclusion: Higher consumption of coffee was associated
with lower risk for death in African Americans, Japanese Americans, Latinos, and
whites. Primary Funding Source: National Cancer Institute.
PMID- 28693035
TI - K2P2.1 (TREK-1)-activator complexes reveal a cryptic selectivity filter binding
site.
AB - Polymodal thermo- and mechanosensitive two-pore domain potassium (K2P) channels
of the TREK subfamily generate 'leak' currents that regulate neuronal
excitability, respond to lipids, temperature and mechanical stretch, and
influence pain, temperature perception and anaesthetic responses. These dimeric
voltage-gated ion channel (VGIC) superfamily members have a unique topology
comprising two pore-forming regions per subunit. In contrast to other potassium
channels, K2P channels use a selectivity filter 'C-type' gate as the principal
gating site. Despite recent advances, poor pharmacological profiles of K2P
channels limit mechanistic and biological studies. Here we describe a class of
small-molecule TREK activators that directly stimulate the C-type gate by acting
as molecular wedges that restrict interdomain interface movement behind the
selectivity filter. Structures of K2P2.1 (also known as TREK-1) alone and with
two selective K2P2.1 (TREK-1) and K2P10.1 (TREK-2) activators-an N-aryl
sulfonamide, ML335, and a thiophene-carboxamide, ML402-define a cryptic binding
pocket unlike other ion channel small-molecule binding sites and, together with
functional studies, identify a cation-pi interaction that controls selectivity.
Together, our data reveal a druggable K2P site that stabilizes the C-type gate
'leak mode' and provide direct evidence for K2P selectivity filter gating.
PMID- 28693037
TI - Sensitivity Analysis for Unmeasured Confounding: E-Values for Observational
Studies.
PMID- 28693039
TI - Moderate Coffee Intake Can Be Part of a Healthy Diet.
PMID- 28693040
TI - Is Coffee Consumption Associated With Lower Risk for Death?
PMID- 28693038
TI - Coffee Drinking and Mortality in 10 European Countries: A Multinational Cohort
Study.
AB - Background: The relationship between coffee consumption and mortality in diverse
European populations with variable coffee preparation methods is unclear.
Objective: To examine whether coffee consumption is associated with all-cause and
cause-specific mortality. Design: Prospective cohort study. Setting: 10 European
countries. Participants: 521 330 persons enrolled in EPIC (European Prospective
Investigation into Cancer and Nutrition). Measurements: Hazard ratios (HRs) and
95% CIs estimated using multivariable Cox proportional hazards models. The
association of coffee consumption with serum biomarkers of liver function,
inflammation, and metabolic health was evaluated in the EPIC Biomarkers subcohort
(n = 14 800). Results: During a mean follow-up of 16.4 years, 41 693 deaths
occurred. Compared with nonconsumers, participants in the highest quartile of
coffee consumption had statistically significantly lower all-cause mortality
(men: HR, 0.88 [95% CI, 0.82 to 0.95]; P for trend < 0.001; women: HR, 0.93 [CI,
0.87 to 0.98]; P for trend = 0.009). Inverse associations were also observed for
digestive disease mortality for men (HR, 0.41 [CI, 0.32 to 0.54]; P for trend <
0.001) and women (HR, 0.60 [CI, 0.46 to 0.78]; P for trend < 0.001). Among women,
there was a statistically significant inverse association of coffee drinking with
circulatory disease mortality (HR, 0.78 [CI, 0.68 to 0.90]; P for trend < 0.001)
and cerebrovascular disease mortality (HR, 0.70 [CI, 0.55 to 0.90]; P for trend =
0.002) and a positive association with ovarian cancer mortality (HR, 1.31 [CI,
1.07 to 1.61]; P for trend = 0.015). In the EPIC Biomarkers subcohort, higher
coffee consumption was associated with lower serum alkaline phosphatase; alanine
aminotransferase; aspartate aminotransferase; gamma-glutamyltransferase; and, in
women, C-reactive protein, lipoprotein(a), and glycated hemoglobin levels.
Limitations: Reverse causality may have biased the findings; however, results did
not differ after exclusion of participants who died within 8 years of baseline.
Coffee-drinking habits were assessed only once. Conclusion: Coffee drinking was
associated with reduced risk for death from various causes. This relationship did
not vary by country. Primary Funding Source: European Commission Directorate
General for Health and Consumers and International Agency for Research on Cancer.
PMID- 28693041
TI - Rethinking How to Measure the Appropriateness of Cervical Cancer Screening.
PMID- 28693042
TI - Evaluating Corneal Fluorescein Staining Using a Novel Automated Method.
AB - Purpose: To evaluate interobserver concordance in measured corneal fluorescein
staining (CFS) using the National Eye Institute/Industry (NEI) grading scale and
the Corneal Fluorescein Staining Index (CFSi), a computer-assisted, objective,
centesimal scoring system. Methods: We conducted a study to evaluate CFS in
clinical photographs of patients with corneal epitheliopathy. One group of
clinicians graded CFS in the images using the NEI while a second group applied
the CFSi. We evaluated the level of interobserver agreement and differences among
CFS scores with each method, level of correlation between the two methods, and
distribution of cases based on the CFS severity assigned by each method. Results:
The level of interobserver agreement was 0.65 (P < 0.001) with the NEI, and 0.99
(P < 0.001) with the CFSi. There were statistically significant differences among
clinicians' measurements obtained with the NEI (P < 0.001), but not with the CFSi
(P = 0.78). There was a statistically significant correlation between the CFS
scores obtained with the two methods (R = 0.72; P < 0.001). The NEI scale
allocated the majority of cases (65%) within the higher quartile in the scale's
severity (12-15/15). In contrast, the CFSi allocated the majority of cases (61%)
within the lower quartile in the scale's severity (0-25/100). Conclusions: The
CFSi is easy to implement, provides higher interobserver consistency, and due to
its continuous score can discriminate smaller differences in CFS. Reproducibility
of the computer-based system is higher and, interestingly, the system allocates
cases of epitheliopathy in different severity categories than clinicians do. The
CFSi can be an alternative for objective CFS evaluation in the clinic and in
clinical trials.
PMID- 28693043
TI - Sensitivity Analysis in Observational Research: Introducing the E-Value.
AB - Sensitivity analysis is useful in assessing how robust an association is to
potential unmeasured or uncontrolled confounding. This article introduces a new
measure called the "E-value," which is related to the evidence for causality in
observational studies that are potentially subject to confounding. The E-value is
defined as the minimum strength of association, on the risk ratio scale, that an
unmeasured confounder would need to have with both the treatment and the outcome
to fully explain away a specific treatment-outcome association, conditional on
the measured covariates. A large E-value implies that considerable unmeasured
confounding would be needed to explain away an effect estimate. A small E-value
implies little unmeasured confounding would be needed to explain away an effect
estimate. The authors propose that in all observational studies intended to
produce evidence for causality, the E-value be reported or some other sensitivity
analysis be used. They suggest calculating the E-value for both the observed
association estimate (after adjustments for measured confounders) and the limit
of the confidence interval closest to the null. If this were to become standard
practice, the ability of the scientific community to assess evidence from
observational studies would improve considerably, and ultimately, science would
be strengthened.
PMID- 28693044
TI - Venous Intervention Improves Patient Outcomes.
AB - INTRODUCTION: The healing of venous ulcers is difficult, and several sources
indicate a multidisciplinary plan of care as the best approach to the healing of
these wounds. MATERIALS AND METHODS: Seventy-five patients with suspected venous
disease being treated at Northern New Jersey Medical Center were assessed by
dedicated interventional radiology physicians as part of Wound Center protocol.
Of those patients, 27 required diagnostic testing, such as CT venogram or
venography. Of these patients, 11 were determined to be appropriate candidates
and underwent surgical intervention, such as venous ablation or vein stenting.
RESULTS: Results support continued referral for venous interventions. Of the 75
patients referred for assessment, 27 required diagnostic testing, and 11 of those
patients met criteria for intervention and treatment. Of the 11 patients who
underwent surgical intervention, 100% experienced success in reduction of one or
more cardinal signs of inflammation, and all patients with open wounds
experienced either reduction in wound size and, more commonly, complete wound
closure. CONCLUSION: Adding venous evaluation referral to wound center protocol
in patients with suspected venous disease improved healing outcomes, thus
improving quality of life.
PMID- 28693045
TI - Hiatal Hernia Repair: Current Evidence for Use of Absorbable Mesh to Reinforce
Hiatal Closure.
AB - INTRODUCTION: There continues to be debate regarding the best surgical technique
for the treatment of paraesophageal hernias. While laparoscopic and robotic
approaches are widely employed around the world, the benefits of mesh use to
reinforce hiatal closure are still not well established. The goal of this
manuscript is to describe the currently available results with biologic and
bioabsorbable meshes for treatment of paraesophageal hernias, particularly with
reference to the rate of recurrence. MATERIALS AND METHODS: A systematic review
of the literature was conducted to identify studies describing treatment of
hiatal hernias with biologic or bioabsorbable mesh. The available studies were
categorized as comparative (when authors compared results with a different
patient cohort undergoing suture repair of the hiatus without mesh reinforcement)
and non-comparative, and organized by levels of evidence. RESULTS: We identified
two randomized control trials, a long-term follow-up to one of the trials, a
prospective case control study, one retrospective case control study, two meta
analyses of the above-mentioned studies, as well as 11 non-comparative studies,
which included two prospective, 10 retrospective, and two case series. Most
studies involved the use of different biologic meshes, while bioabsorbable mesh
use was only described in four of the retrospective studies mentioned. The
results are variable, however, most authors found a benefit from hiatal closure
reinforcement with mesh. CONCLUSIONS: The available literature lacks definitive
evidence to support the use of biologic or bioabsorbable materials to reinforce
hiatal closure in the cure of paraesophageal hernias. Further studies are needed
to assess newer materials and longer-term effects of existing products.
PMID- 28693046
TI - So You Think You Don't Plunge? An Assessment of Far Cortex Drill Tip Plunging
Based on Level of Training.
AB - INTRODUCTION: Drill bit tip plunging past the far cortex places critical
anatomical structures at risk. This study measured plunging past the far cortex
based on level of training. The time required for screw placement when a depth
gauge was used to measure bone tunnel depth was compared to the time required for
screw placement when bone tunnel depth was measured in real time. MATERIALS AND
METHODS: Thirty orthopedic surgery staff with 1-37 years of experience applied 10
hole plates to cadaveric limbs. Procedures were performed using two different
drilling systems. Time and plunge depth were recorded. RESULTS: Penetration past
the far cortex ranged from an average of 11.9 mm in the novice group to an
average of 6.1 mm in the experienced group (P <0.001). The time required to drill
and place a screw decreased by an average of 14 seconds per screw when depth
gauge use was eliminated. CONCLUSIONS: Penetration past the far cortex occurred
at all levels of training, but decreased with increased levels of experience.
Real time measurement of bone tunnel length decreased total drilling time. The
time saved with real time measurement decreased with increased level of
experience.
PMID- 28693047
TI - Thermal Effect of J-Plasma(r) Energy in a Porcine Tissue Model: Implications for
Minimally Invasive Surgery.
AB - OBJECTIVE: To evaluate tissue effect of J-Plasma(r) (Bovie Medical Corporation,
Clearwater, Florida) in porcine liver, kidney, muscle, ovarian, and uterine
tissue blocks. DESIGN: Prospective study utilizing porcine tissue blocks to
evaluate the thermal spread of J-Plasma(r) device on liver, kidney, muscle,
ovarian, and uterine tissue at various power settings, gas flow, and exposure
times. MATERIALS AND METHODS: J-Plasma(r) helium was used in porcine liver,
kidney, and muscle tissue at 20%, 50%, and 100% power, and 1 L/min, 3 L/min, and
5 L/min gas flow at one, five, and 10-second intervals. J-Plasma(r) was then used
in ovarian and uterine tissue at maximum power and gas flow settings in intervals
of one, five, 10, and 30 seconds. Histologic evaluation of each tissue was then
performed to measure thermal spread. RESULTS: Regardless of tissue type,
increased power setting, gas flow rate, and exposure time correlated with greater
depth of thermal spread in liver, kidney, and muscle tissue. J-Plasma(r) did not
exceed 2 mm thermal spread on liver, kidney, muscle, ovarian, and uterine tissue,
even at a maximum setting of 100% power and 5 L/min gas flow after five seconds.
Prolonged exposure to J-Plasma(r) of up to 30 seconds resulted in increased
length and width of thermal spread of up to 12 mm, but did not result in
significantly increased depth at 2.84 mm. CONCLUSIONS: The J-Plasma(r) helium
device has minimal lateral and depth of thermal spread in a variety of tissue
types and can likely be used for a multitude of gynecologic surgical procedures.
However, further studies are needed to demonstrate device safety in a clinical
setting.
PMID- 28693048
TI - The Use of Branched Endografts for the Aortic Arch in the Endovascular Era.
AB - The endovascular realm has steadily increased its footing in the treatment of the
aorta and all of its territories since the foundational case in 1990 by Parodi.
The aortic arch, however, continues to be one of the last bastions for treatment
via open surgery, which remains the gold standard. Significant comorbidity and
prior cardiac surgery prevent open surgery from being the only preferred option,
allowing novel endovascular procedures to be considered. Since 1999, more
advanced endovascular systems have been created by companies such as Cook
Medical, Bolton Medical, Medtronic, Endospan, Gore Medical, and, recently,
Kawasumi. The unique shape and angulation of the aortic arch often require the
use of custom-made grafts, though arch reconstruction may also include in situ or
back-table physician alterations to off-the-shelf devices. The goal of branched
endografts is to exclude the aneurysm, while maintaining flow to supra-aortic
trunk vessels. Technical success and device durability are limited by the
physical constraints of the aortic arch, though greater experience may yield
better patient outcomes. Typically, the initial stent-graft (SG) is introduced
and deployed into the arch first. Bridging SG are then inserted via axillary or
carotid access. Most often, the bridging SG extends from the innominate branch to
the distal innominate, and from the left carotid branch to the left common
carotid. The major concern is that manipulation of catheters and wires, both
within the carotid arteries and aortic arch, create the potential for emboli
leading to stroke and paraplegia. The development of endovascular-only techniques
for aortic arch pathology will only increase with the aging population of the
United States and associated accumulation of comorbidities, making open surgery
too grave of a risk.
PMID- 28693049
TI - Hybrid Repair Techniques for Complex Aneurysms and Dissections Involving the
Aortic Arch and Thoracic Aorta.
AB - Aortic aneurysms involving the ascending aorta, aortic arch, and descending
thoracic aorta have been a challenging entity to surgically treat for over 60
years. Despite the mortality of the disease, early open surgical procedures also
had significant morbidity and mortality. The inherent risk in treating multiple
anatomic segments simultaneously led to the innovation of the staged elephant
trunk (ET) approach by Borst in 1983. To avoid the thoracotomy and associated
complications related to the second stage of the procedure, an endovascular
completion paradigm was begun by Volodos in 1991. This theoretical hybrid
technique combinined shorter and less elaborate open supra-aortic trunk
debranching with less invasive endovascular exclusion and has grown since then in
terms of different approaches and case volume. The rise of thoracic endovascular
aortic repair (TEVAR) combined with debranching bypass has allowed certain
lesions to be treated without a large scale intrathoracic open surgical
procedure. The complexity and extensiveness of certain lesions, however, has
necessitated a hybrid approach such as the frozen elephant trunk (FET) and the
standard ET with second stage TEVAR. The former has been used to treat multifocal
degenerative aneurysms, chronic dissections with aneurysm, and acute extensive
dissections. After conventional proximal aortic replacement, a stent-graft (SG)
is delivered antegrade through the transected arch where it is sutured proximally
and then "frozen" distally via endovascular means. The FET has the advantage of
avoiding a second stage, but potentially introduces a greater rate of spinal cord
ischemia compared to the standard elephant trunk. Improvements on the FET
procedure have included the development of more advanced hybrid SG such as the
Vascutek(r) Thoraflex? Hybrid graft (Vascutek Ltd, Scotland, UK), which consists
of a distal en,dograft sealed to a proximal four-branched Vascutek Gelweave?
Vascutek Ltd, Scotland, UK) and incorporated sewing collar. While open surgery
continues to be a component of complex aortic arch aneurysms, the development of
hybrid devices that can bridge the gap between open and endovascular surgery will
continue to flourish.
PMID- 28693050
TI - Long-Term Results of Fixation-Free Incisional Hernia Repair Using a Tentacle
Shaped Implant.
AB - INTRODUCTION: The fixation and the overlap of the mesh represent an open issue in
incisional hernia repair. An exclusively designed prosthesis has been developed
to assure a suture-free repair and a broader coverage of the abdominal wall. This
study describes the long-term results of incisional hernia procedures carried out
positioning a tentacle-shaped implant through a specifically developed surgical
technique. MATERIALS AND METHODS: A proprietary symmetrically-shaped flat mesh
constituted by a large central body with integrated radiating arms was used to
repair incisional hernias in 68 patients. The prosthesis was placed in
preperitoneal/retromuscular sublay. The friction of the straps passing through
myotendineal structures of the abdomen was intended to assure an adequate grip to
firmly hold the device in place with a broad overlap of the hernia defect in a
fixation-free fashion. All tentacle straps were positioned through a special
needle passer crossing the abdominal wall laterally from the defect borders then
cut short in the subcutaneous layer. RESULTS: In a long-term follow-up of 12 to
96 months (mean 58 months), 11 seromas occurred. No infections, hematomas,
chronic pain, mesh dislocation, or recurrence have been reported. CONCLUSIONS:
The tentacle strap system of the prosthesis effectively ensured reduced skin
incision and an easier implant placement avoiding the need for suturing the mesh.
Regularly performed computed tomography (CT) and ultrasound (US) investigations
proved that the arms of the implant ensured a proper orientation and
stabilization of the mesh in association with a broad defect overlap. The
specifically developed surgical procedure showed a quick postoperative recovery,
a very low complication rate, and no recurrences, even in the long-term.
PMID- 28693051
TI - Whole genome SNP genotyping in a family segregating developmental dysplasia of
the hip detected runs of homozygosity on chromosomes 15q13.3 and 19p13.2.
AB - Developmental dysplasia of the hip (DDH) is one of the most prevalent
developmental orthopedic diseases worldwide. DDH is a spectrum of anatomical
abnormalities of the hip joint and is characterized by premature arthritis in
later life. Sporadic cases have been reported more frequently; however, some
studies have reported families segregating DDH. Studies have suggested that the
genetic factors play a significant role in the development of DDH. In order to
detect genetic defect underlying DDH, we performed Sanger sequencing of all DDH
associated genes, whole genome SNP genotyping and exome sequencing in a Saudi
family with four individuals having DDH. Sanger sequencing of all known genes did
not identify any pathogenic variant. Genotype data analysis using
HomozygosityMapper identified shared homozygous regions on chromosome 15q13.3 and
chromosome 19p13.2 flanked by rs17228178-rs1534200 and rs466123-rs2112461,
respectively. These data were also analyzed by cnvpartition software for
identification of DDH associated copy number variations (CNV). A shared copy
number gain of approximately 15 kb on chr6p21.32 (chr6:33 053 906-33 069 893) was
discovered in all affected individuals. Partial gain of this region has also been
found in unaffected sibling of this family. Exome data did not reveal any
candidate sequence variant. Whole genome sequencing is required to identify deep
intronic variants in the shared homozygous regions. Identification of genetic
variants involved in pathogenesis of DDH may open up interesting perspectives
into the function of the gene(s) in hip joint development.
PMID- 28693053
TI - [Paying more attentions to the research of disease burden and clinical phyenotype
in patients with severe asthma].
PMID- 28693052
TI - Severity of Baclofen Self-Poisoning Linked to Psychiatric Co-morbidity in Alcohol
Dependent Patients: Better Measurement of Risk and Benefit.
PMID- 28693054
TI - [Paradoxical septal motion: indicator of right ventricular overload].
PMID- 28693055
TI - [The relationship between smoking status and epidermiology of asthma in people
aged over 14 years in China].
AB - Objective: To study the relationship between bronchial asthma and smoking status
in Chinese people. Methods: Asthma epidemiological survey and stratified-cluster
random method survey were performed in residents over 14 years in 8 provinces
(cities) of China from February 2010 to August 2012. Asthma was diagnosed based
upon case history, clinical signs and lung function test. Smoking status was
investigated by questionnaire. Results: Sampling population was 180 099 and 164
215 were valid. A total of 2 034 subjects were diagnosed as asthma including 79
692 men and 84 523 women. The overall prevalence rate of asthma was 1.24% (2
034/164 215). Smokers were 23.8% (39 137/164 215) in the whole population.
Smokers were 34.5% (702/2 034) in asthmatic patients, compared with 23.7% (38
435/162 181) in no-asthmatic population. The incidence of asthma was 1.79% and
1.06% in smokers and non-smokers respectively (P<0.001), suggesting that OR of
smoking was 1.70 (95% CI 1.55-1.86, P<0.001). According to asthma control test
(ACT) score, the level of asthma control in non smoking group was higher than
that in smoking group(43.2% vs 35.3%). The times of hospitalization due to acute
exacerbations(0.51 vs 0.41 events/person/year), total hospitalization rate(27.35%
vs 20.12%), annual emergency room visits (0.80 vs 0.60 events/person/year) and
emergency room visit rate (31.77% vs 24.47%) were all much higher in smoking
asthmatic patients than those in non smoking asthmatic patients, indicating that
the level of asthma control in smoking patients was significantly worse than in
non smoking patients. Conclusions: The smoking rate in Chinese people over 14
years is still high. The prevalence rate of asthma in smokers is significantly
higher than that of non-smokers. The level of asthma control in smokers is
significantly worse than that in non smokers.
PMID- 28693056
TI - [The clinical characteristics of pulmonary benign metastasizing leiomyoma].
AB - Objective: Pulmonary benign metastasizing leiomyoma (PBML) is a rare entity that
leiomyoma of uterus metastasized to the lung. The clinical characteristics of
this rare disease were analyzed in this article. Methods: The detailed clinical
records of 7 patients diagnosed as PBML at Peking Union Medical College Hospital
between January 2001 and June 2015 were reviewed. Results: All patients were
women with median age of 44 years (range 28-62). Symptoms included dyspnea (2/7),
chest pain (1/7), cyanosis (1/7), cough (1/7) and bloody sputum (1/7), while 4/7
cases were asymptomatic. Six patients had the past-history of leiomyoma of uterus
20 months to 14 years ago among whom 5 patients received hysterectomy. Chest CT
showed bilateral, random-distributed multiple round solid nodules, or diffuse
distributed miliary nodules, or single solid nodule, even some small cavities.
Extra-pulmonary metastasis was found in left superclavicular lymph node (1 case)
and right heart (1 case). Histological tissues were obtained by video-assisted
thoracic surgery lung biopsy (4/7), mass resection on tricuspid valve (1/7),
transbronchil lung biopsy (1/7), and CT-guided percutaneous lung biopsy (1/7).
Pathology showed an interlacing pattern by spindle cells having elongated nuclei
without cellular atypia. Ki-67 index was less than 1%. Molecules such as smooth
muscle antibody, estrogen receptor (ER) and progestrone receptor (PR) were
positive in immunohistochemistry staining. Neither letrozole nor zoladex was
effective. Two patients responded to bilateral adnexectomy, presenting as shrunk
nodules. No relapsed disease was seen in one patient with single nodule after
resection. There was only one patient with disease-related mortality, whose chest
CT showed milliary nodules. Conclusion: Although CT findings of PBML are similar
to malignancies, the clinical outcome is good. Despite the positive expression of
ER and PR, the effectiveness of hormone related treatment is limited. And
periodical follow up is suggested even to those uneventful patients.
PMID- 28693057
TI - [The value of the excursion of diaphragm tested by ultrosonography to predict
weaning from mechanical ventilation in ICU patients].
AB - Objective: To evaluate the excursion of the diaphragm and analyze the value in
predicting weaning from mechanical ventilation in intensive care unit patients.
Methods: The patients with mechanical ventilation (>48 hours) in ICU at Hebei
Forth Medical University Hospital from June 2014 to December were classified into
a success group or a failure group according to the weaning outcome. T-piece
spontaneous breathing (SBT), airway occlusion pressure at 0.1 sec (P(0.1)) and
maximal inspiratory pressure (MIP), rapid shallow breathing index (RSBI) and
P(0.1)/MIP were measured or calculated. During the period of the 1st hour SBT,
the excursion of diaphragm was measured with ultrasonography. The predictive
value of each parameter to weaning was evaluated with ROC curve. Results: A total
of 98 patients were enrolled in this study, including 74 successfully weaning and
24 failed. There were significant differences between two groups(success group
and failure group) in P(0.1)[(2.00+/-2.00)cmH(2)O (1 cmH(2)O=0.098 kPa) vs
(3.00+/-2.75)cmH(2)O, P<0.05], RSBI (39.14+/-16.81 vs 52.00+/-19.18, P<0.05),
left diaphragmatic excursion [(1.12+/-0.97)cm vs (0.69+/-1.00)cm, P<0.001], right
diaphragmatic excursion(1.87+/-0.75)cm vs (1.17+/-0.76)cm, P<0.001] and mean
value of left and right diaphragmatic excursion [(1.57+/-0.52)cm vs (0.83+/
0.53)cm, and P<0.001]. The ventilation time [2.00(2.00-4.00)d vs 4.00(2.00
5.00)d], ICU hospital lengths of stay [4.50(3.00-7.25)d vs 8.50(6.25-15.25)d] and
total hospital lengths of stay[20.00(15.00-25.25)d vs 25.00(20.25-37.25)d] were
also statistically significant in success group and failure group respectively
(all P<0.05). The cutoff value of diaphragmatic excursion for predicting
successful extubation was determined to be 1.14 cm by ROC curve analysis. The
sensitivity of diaphragmatic excursion to predict successful weaning was 89.2%
and the specificity was 75.0%, the AUC(ROC) was 0.849. Conclusion: As an early
predictor of diaphragmatic dysfunction, diaphragmatic excursion is probably
superior to the traditional parameters in predicting weaning from ventilator in
ICU patients.
PMID- 28693058
TI - [A prospective multi-center trial of non-interventional and observational study
of lenalidomide in Chinese patients with multiple myeloma].
AB - Objective: To evaluate the efficacy and safety of lenalidomide in a real-world
clinical practice in Chinese patients with multiple myeloma (MM). Methods: It was
a prospective, multi-center, observational study. A total of 165 consecutive
patients with MM treated with lenalidomide-based regimens were enrolled in 12
hospitals from June 2013 to November 2015. Relevant information was recorded,
such as baseline clinical data, cytogenetic abnormalities, treatment regimens,
and duration of treatment, safety, and survival. Results: (1)There were 126
relapsed and refractory MM (RRMM) patients, 25 newly diagnosed patients and 19
maintenance patients. The evaluable RRMM patients accounted for 120 cases, among
which 74 cases(61.7%) reached the partial response (PR) or above, and a very good
partial response (VGPR) in 16 patients (13.3%), a complete response (CR) in 14
cases (11.7%), a strictly complete response (sCR) in 4 cases (3.3%). Thus, a VGPR
or above in 34 patients accounted for 28.3%. (2)The median follow-up was 13
months, the median time to progression 12 months. The median survival after
receiving lenalidomide was 19 months, and the median overall survival (OS) was 62
months. (3) The univariate analysis in 120 RRMM patients suggested that
prognostic factors for significant improvement in PFS included normal karyotype,
international staging system (ISS) I-II, t(4; 14) negative (detected by
fluorescence in situ hybridization), non-bortezomib resistance and response to
previous regimens. As to OS, non-bortezomib resistance, response to previous
regimens and non-primary refractoriness were positive factors. Multivariate
analysis showed that the response to previous regimens (PR or better) was an
independent good prognostic factor for progress-free survival(PFS), non
bortezomib resistance and non-primary refractoriness for OS. (4) Grade 3 or 4
adverse events that occurred in more than 10% of all enrolled patients were
neutropenia (12.7%), leukocytosis(11.5%) and thrombocytopenia (12.7%). Owing to
intolerance of toxic side effects, 7 cases withdrew lenalidomide. Conclusions: No
matter what combination, regimens containing lenalidomide are effective to RRMM
patients with overall response rate 61.7%, a time to progression 12 months and an
overall survival 62 months.The toxicity is quite tolerable and manageable. In
addition, the response to previous treatment (reached PR or above) is the
independent good prognostic factor for PFS, non-bortezomib resistance and non
primary refractoriness for OS. Clinical trail registration: Clinicaltrials.gov,
NCT01947309.
PMID- 28693059
TI - [The effects and mechanisms of berberine on proliferation of papillary thyroid
cancer K1 cells induced by high glucose].
AB - Objective: To study the effect and mechanisms of berberine (BBR) on the
proliferation of papillary thyroid cancer K1 cells induced by high glucose.
Methods: K1 cells were cultured under 5.5 mmol/L or 25 mmol/L glucose condition
with or without different concentration of BBR (0, 10, 40 and 80 MUmol/L) for 24
hours. The proliferations of K1 cells in each condition were detected by MTT.
Western blot was used to measure the expression of nuclear factor erythroid 2
related factor 2(Nrf2), phosphoinositide 3-kinase (PI3K), protein kinase B (Akt)
and phosphorylated-Akt (p-Akt). The distribution pattern of Nrf2 in K1 cells was
determined using immunofluorescent staining. Results: Compared with 5.5 mmol/L
condition, the proliferation rate [(126.64+/-5.41) % vs (87.31+/-3.67)%],
expression levels of PI3K (0.425+/-0.019 vs 0.272+/-0.039), p-Akt/Akt (0.446+/
0.021 vs 0.168+/-0.035) and Nrf2 (0.597+/-0.014 vs 0.308+/-0.026), and Nrf2
distribution (93.0% vs 23.1%) in nuclear of K 1 cells under 25 mmol/L condition
were significantly elevated, respectively (all P<0.01). Addition of BBR in 25
mmol/L condition dose dependently (10, 40, 80 MUmol/L) lowered the proliferation
rate of K1 cells [(111.76+/-4.10)%, (70.03+/-2.18)%, (32.41+/-3.76)% vs (126.64+/
5.41)%, all P<0.05], and suppressed the expression of PI3K, p-Akt/Akt, Nrf2, and
Nrf2 nuclear distribution (P<0.05). Conclusions: BBR dose dependently inhibited
the proliferation of high glucose-induced K1 cells. This effect was associated
with the suppression on of PI3K/Akt signaling activation, Nrf2 expression and its
nuclear translocation.
PMID- 28693061
TI - [Paying more attention to clinical clues in tracing the origin of special cases
with diabetes-like symptoms].
PMID- 28693060
TI - [An analysis of four cases of misdiagnosed primary lymphocytic hypophysitis].
AB - To improve the differential diagnosis of sellar region mass, 4 cases with sellar
mass and misdiagnosed as lymphocytic hypophysitis (LYH) were reviewed
retrospectively.The 4 patients (2 male and 2 female) aged 20-60 years old were
all presented with symptoms of headache, polydipsia and polyuria.Biochemical
studies confirmed the diagnoses of central diabetes insipidus and
hypopituitarism.Head MRI scans showed LYH like image for all the cases, and,
thus, high dose methylprednisolone pulse therapy (HDMPT) was applied to the
patients.Their symptoms deteriorated and the sellar mass enlarged after a short
period of partial improvement.Operations were performed in all the
patients.Histology study showed craniopharyngioma with abscess, primary abscess,
secondary hypophysitis caused by Wegener's granulomatosis, and germinoma with
secondary hypophysitis, respectively.In conclusion, surgery or biopsy is
necessary for those who presented with sellar region mass and was suspected to be
with LYH, but with poor response or even worse after HDMPT.
PMID- 28693062
TI - [the risk stratification and treatment of smoldering multiple myeloma].
PMID- 28693063
TI - [Gut microbiota nd nervous system diseases in the elderly].
PMID- 28693064
TI - [Subclinical Cushing's syndrome in patients with incidental adrenal tumor].
PMID- 28693065
TI - [Advances in clinical research of DNA reservoir in HIV infected patients].
PMID- 28693066
TI - [Fifth Chinese national consensus report on the management of Helicobacter pylori
infection].
AB - The fifth national consensus conference on the management of Helicobacter pylori
(H.pylori) infection organized by Chinese Medical Association, Chinese Society of
Gastroenterology, H. pylori and Peptic Ulcer Study Group was held at Hangzhou,
Zhejiang Province on December 15-16, 2016.More than 80 members of the study group
and experts in the field of H. pylori research and gastroenterology attended the
meeting.Consensus preparatory group was established to draft the related
statements.The quality of evidence and strength of recommendation were evaluated
by GRADE system.The Delphi method using an anonymous electronic system was
adopted to develop the consensus of relevant statements.Expert advices about the
established statements were firstly consulted through the emails.After two rounds
of consultation, the preliminary statements of consensus were discussed and
modified in the conference item by item.A total of 21 core members voted for the
final version, which contained a total of 48 statements and was divided into 6
parts, including indications for H. pylori eradication, diagnosis, treatment, H.
pylori and gastric cancer, H. pylori infection in special populations, H. pylori
and gastrointestinal microbiota.
PMID- 28693067
TI - [Chinese expert consensus for non-antiinfective effects and clinical use of
macrolides].
AB - Important/potential value of macrolides has been proved in the management of
chronic respiratory diseases by increasing basic and clinical trials.Through
three face-to-face discussions, 10 experts examined important data and drafted
this consensus related to macrolides: (1) mechanism of non-antiinfective effects;
(2) clinical use in chronic respiratory diseases; (3) cautions of long-term
use.The mechanism out of non-antiinfective effects includes anti-inflammatory
effect, modifying airway secretion, immune-regulation related to antibacterial
effect, corticoid saving effect and anti-viral effect.The efficacy of long-term
use of low-dose macrolides is definitely confirmed in diffuse panbronchiolitis,
chronic rhinosinusitis. It is considerably used in bronchiectasia, cystic
fibrosis, severe asthma and chronic obstructive pulmonary disease. Further
studies should be conducted in cryptogenic organizing pneumonia and respiratory
viral infection. It should be paid attention to its possible adverse effects
(including drug interactions, cardiac toxicity, ototoxicity and disturbance of
intestinal flora) and drug resistance in long-term use.A Chinese consensus for
non-antiinfective effects and clinical use of macrolides is developed for the
first time, which aims to expand their rational use and the further research.
PMID- 28693068
TI - [Strengthen and standardize the diagnosis and treatment of hyperuricemia in
kidney diseases].
PMID- 28693069
TI - [Enhance the ability of recognition and management for the functional rheumatic
symptoms].
PMID- 28693070
TI - [Expression of annexin A1 in peripheral blood cells of Naive rheumatoid arthritis
patients and its influencing factors].
AB - Objective: To explore the expression of Annexin a1 (AnxA1) mRNA in peripheral
blood mononuclear cells (PBMC) from Naive rheumatoid arthritis (RA) patients and
healthy controls and to investigate its influencing factors. Methods: Thirty
Naive RA patients and 36 healthy controls were recruited from the First
Affiliated Hospital of Harbin Medical University between May 2013 and January
2015.All RA patients were fulfilled the classification criteria of ACR in
1987.Clinical characteristics and laboratory indexes were collected.Real time
polymerase chain reaction (RT-PCR) was used to measure AnxA1 and Foxp3 mRNA
expression respectively.Serum TNF-alpha, IL-17 and IL-10 levels in each group was
determined separately by enzyme linked immunosorbent assay (ELISA). Furthermore,
correlations between the expression of AnxA1 mRNA and clinical characteristics,
laboratory parameters, Foxp3 mRNA, serum IL-17, TNF-alpha, IL-10 level in Naive
RA patients were analyzed. Results: The expressions of AnxA1 mRNA in PBMC of
Naive RA patients were lower than that of healthy controls [0.12 (0.05-0.30)
versus 1.66 (0.40-2.68), P<0.05]. The Foxp3 mRNA expressions in PBMC of Naive RA
patients were also lower than that of healthy controls [0.77 (0.39-1.89) versus
2.93 (2.65-3.49), P<0.05], while serum TNF-alpha, IL-17, and IL-10 levels of
Naive RA patients were higher than those of healthy controls (P<0.05). The
expression of AnxA1 was positively associated with the expression of Foxp3 mRNA
(r(s)=0.513, P<0.05) and negatively associated with the serum IL-17 level (r(s)=
0.381, P<0.05). But there were no correlations between expression of AnxA1 in
PBMCs from Naive RA patients with the TNF-alpha, IL-10 level, clinical
characteristics (sex, age, disease duration and disease activity) and the
laboratory indexes (RF, Anti-CCP antibody, ESR and CRP). The expression of Foxp3
mRNA and the serum IL-17 level was the independent influencing factor.
Conclusions: The reduced expression of AnxA1 may associate with the reduced
expression of Foxp3 and the increased IL-17 level in Naive RA patients.It
suggested that AnxA1 may play a key role in immune regulation and anti
inflammatory process in the pathogenesis of RA.
PMID- 28693072
TI - [Comparison of posterior fossa decompression with and without duraplasty for
surgical management for adult Chiari malformation type I].
AB - Objective: To evaluate and compare the efficacy between posterior fossa
decompression without duraplasty (PFD) and posterior fossa decompression with
duraplasty (PFDD) in the surgical management for adult Chiari I malformation.
Methods: Fifty-seven patients suffered from Chiari malformation type I were
treated in Department of Neurosurgery, Henan Provincial People's Hospital from
August 2008 to October 2013. Twenty-three patients received posterior fossa
decompression without duraplasty and the other 34 patients received posterior
fossa decompression with duraplasty. The clinical results were retrospectively
analyzed to compare the efficacy of two different surgical approaches. Results:
There was no death or severe neurological dysfunction case in 57 patients of the
two groups. Patients undergoing PFD had shorter length of hospital stay[(13.7+/
3.5) d vs (16.2+/-4.1) d, P<0.05]and surgical time[(98.7+/-22.1) min vs (132.3+/
39.6)min, P<0.05]. Cerebrospinal fluid-related complications and intracranial
infection were more common in patients undergoing PFDD[(0/23, 0) vs (8/34,
23.5%), P<0.05]. Clinical improvement was comparable in two groups[(15/23, 65.2%)
vs (26/34, 76.5%), P>0.05]at the one-year follow-up. The rate of syrinx
regression in patients with Syringomyelia was higher in patients undergoing
PFDD[(3/12, 25%) vs (17/22, 77.3%), P<0.05]. Conclusion: For adult patients with
Chiari malformation type I, PFD has the advantages of simple manipulation, short
length of hospital stay and low incidence of cerebrospinal fluid-related
complications and intracranial infection, compared with PFDD. It is comparable to
PFDD in clinical improvement, but the effect of PFD is not as good as that of
PFDD in the aspect of syrinx regression.
PMID- 28693071
TI - [Effect of transcatheter arterial chemoembolization combined with thymosin alpha
1 on the autophagy of immune cells from advanced hepatocellular carcinoma].
AB - Objective: To investigate the effect of transcatheter arterial
chemoembolization(TACE)combined with thymosin alpha1(Talpha1)on the autophagy of
immune cells from advanced hepatocellular carcinoma. Methods: A total of 30
patients with advanced liver cancer enrolled in Lishui Central Hospital from
September 2015 to June 2016 were collected in this study. The average age of
patients was 16-75(56+/-12) years. All patients were treated with TACE after
enrolled in hospital in a week. Patients were divided into TACE group and TACE+
Talpha1 treatment group(15 cases in each group). Patients in TACE group received
a conventional treatment, without any immunotherapy, while the TACE+ Talpha1
treatment group accepted TACE following a subcutaneously injection of 1.6 mg
Talpha1 twice a week for 4 weeks. Flow cytometry was used to detect the T cell
subsets in two groups both before and after TACE treatment for 1, 4 weeks and at
3 months follow-up. Peripheral blood mononuclear cells (PBMC) were isolated by
density gradient centrifugation. The expression of Beclin-1, LC3 protein and mRNA
were detected by Western blot (WB) and PCR respectively. Results: There was no
statistical difference of the percentage of CD3(+) , CD4(+) , CD8(+) T cell
subsets and Beclin-1, LC3 protein and mRNA expression between the two groups
before TACE treatment (P>0.05). The percentage of CD3(+) , CD4(+) , CD8(+) T cell
subsets in TACE+ Talpha1 group at 1 week post-TACE treatment (58.45%+/-16.34%,
38.33%+/-15.16%, 27.31%+/-12.54%), at 4 weeks post-TACE treatment (62.38%+/
18.62%, 43.19%+/-13.86%, 29.54%+/-10.33%) and 3 months follow-up (64.15%+/
13.76%, 41.28%+/-14.65%, 29.38%+/-15.65%) were statistically higher than those in
TACE group at 1 week post-TACE treatment (53.71%+/-11.17%, 32.12%+/-10.53%,
24.45%+/-13.72%) at 4 weeks post-TACE treatment (52.12%+/-14.26%, 31.16%+/
15.43%, 23.39%+/-15.33%) and 3 months follow-up (54.28%+/-13.15%, 32.17%+/
14.98%, 24.34%+/-14.12%) (P<0.05). The Beclin-1, LC3 protein and mRNA expression
in TACE+ Talpha1 group at 1 week post-TACE treatment (protein: 0.57+/-0.08,
2.26+/-0.36, mRNA: 0.62+/-0.11, 2.69+/-0.27), at 4 weeks post-TACE treatment
(protein: 0.66+/-0.09, 3.11+/-0.45, mRNA: 0.78+/-0.13, 3.43+/-0.61) were higher
than those in TACE group at 1 week post-TACE treatment (protein: 0.45+/-0.16,
1.43+/-0.30, mRNA: 0.52+/-0.15, 1.15+/-0.37), at 4 weeks post-TACE treatment
(protein: 0.51+/-0.13, 1.81+/-0.35, mRNA: 0.56+/-0.10, 1.98+/-0.41) ( P<0.05).
But there was no statistically significant difference in the expression of Beclin
1 and LC3 in two groups at 3 months follow-up (P>0.05). Conclusions: TACE
combined with Talpha1 significantly increase the level of autophagy in the immune
cells of patients with advanced primary hepatocellular carcinoma.
PMID- 28693073
TI - [Resting state fMRI study of emotional network in patients with postconcussion
syndrome].
AB - Objective: To discuss functional connectivity changes in the emotional network of
patients with post-concussion syndrome (PCS) and their clinical significance by
resting-state functional magnetic resonance imaging (rs-fMRI). Methods: Twenty
seven patients with PCS were recruited from the Department of Neurosurgery of
Anhui provincial hospital affiliated to Anhui medical university from October
2015 to April 2016, and 27 healthy subjects were recruited as the controls. The
Hamilton Anxiety Scale (HAMA) and The Hamilton Depression Scale (HAMD) were used
to evaluate the emotional state of two groups of subjects. All fMRI data were
preprocessed after RS-fMRI scanning, the left and right amygdala were selected as
region of interest (ROI) to make functional connectivity (FC) calculation with
the whole brain and then the results were did statistical analysis in order to
obtain the altered brain areas of amygdala and whole brain functional
connectivity in the PCS patient, to understand the functional changes of
emotional network. Results: HAMA and HAMD scores of PCS group and the health
controls had significant statistical difference (HAMA: the PCS group 9.8+/-1.5,
the health controls 4.5+/-1.2, P=0.044; HAMD: the PCS group 12+/-1.2, the health
controls was 4.2+/-1.5, P=0.024). Compared with the health controls, the left
amygdala in PCS patients showed decreased FC with left insula, left putamen, left
anterior cingulate gyrus, left inferior orbital frontal gyrus, left medial
superior frontal gyrus, bilateral superior temporal gyrus, left superior temporal
pole, bilateral supramarginal gyrus et al, on the contrary with the increased FC
with right superior orbital frontal gyrus, right middle frontal lobe, right
orbital frontal lobe, right middle frontal gyrus. The right amygdala in PCS
patients showed decreased FC with bilateral putamen, right inferior orbital
frontal gyrus, left insula, bilateral precuneus, bilateral superior temporal
pole, right superior temporal gyrus, right supramarginal gyrus et al. Similarly,
it had the increased FC with the left middle occipital lobe and the left superior
occipital lobe. Conclusion: Abnormal emotional network function of PCS patients
in resting state, which may be one of the reasons that lead to emotional and
cognitive dysfunction in PCS patients.
PMID- 28693074
TI - [Analysis of the correlation between deep medullary veins and clinical prognosis
of middle cerebral artery stroke].
AB - Objective: To investigate the relativity between the distribution of deep
medullary vein (DMV) in patients with middle cerebral artery stroke and clinical
prognosis by using susceptibility-weighted imaging (SWI). Methods: A total of 144
cases of middle cerebral artery stroke patients and 55 healthy volunteers were
retrospectively analyzed from January 2015 to October 2015 in order to
investigate the symmetrical characteristic and the classification of DMV, then 30
cases were followed up. Kappa test was used to consider the consistency of
judging DMV symmetry and type data by two radiologists. Results:Kappa value in
DMV symmetry and DMV type were 0.875 and 0.852. Chi-square test analysis revealed
a statistically significant difference of DMV symmetry between healthy control
and stroke group(chi(2)=31.046, P=0.000). There was correlation between DMV type
and NIHSS score in stroke group (r(s)=0.208, P=0.025). There was no statistically
significant difference of DMV distribution in the different periods of stroke
group (P=0.110). But there was statistically significant difference of DMV
distribution between acute and chronic stroke (P=0.018). Among 30 follow-up
cases, 18 cases with asymmetry DMV changed into symmetry after stroke therapy. In
8 cases with symmetry DMV, the diameter of DMV became smaller after treatment. In
4 cases, DMV had no changes. Conclusions: DMV in patients of MCA stroke are
mostly asymmetry distribution. DMV classification can be used as an imaging
standard to predict the prognosis of stroke patients.
PMID- 28693075
TI - [Preliminavy clinical study of the treatment of hemorrhoids by superselective
embolization of superior rectal artery].
AB - Objective: To investigate the safety and feasibility of the treatment of
hemorrhoids by superselective arterial embolization. Methods: The clinical data
of 15 patients with grade II to IV hemorrhoids were collected who were treated by
superselective SRA embolization.According to the number and shape of SRA in the
vicinity of the dentate line, chosed coils, PVA particles and gelfoam particles,
ethanol and bletilla mixture of gelfoam particles for embolization.And
intraoperative operations, postoperative complications, follow-up treatment
results were observed. Results: The interventional procedures were successfully
accomplished in all 15 cases.The operation time was (30+/-14) min, and the
hospital stay was 1-7 (2.0+/-1.8) days after operation, and the patients
recovered to normal life in 12 hours after the operation.Tenesmus (14/15), pain
(5/15) and low fever (11/15) can alleviate without special treatment. All
patients were follow up (19.0+/-2.6) months, bleeding symptoms were cured,
there's no serious complications. Conclusion: The treatment of hemorrhoids by
transcatheter superselective embolization of superior rectal artery is
technically safe and feasible.
PMID- 28693076
TI - [High mechanical stretch stress promotes degeneration of the human nucleus
pulposus cells through NF-kappab signaling pathway].
AB - Objective: To investigate the effect of high mechanical stretch stress(HMS)on
human nucleus pulposus cells and its regulatory mechanism. Methods: The non
degenerated nucleus pulposus tissue (Pfirrmann=108 mU/ml,
and negative as <108 mU/ml. chi(2) test was used to compare the difference in
positive rates among subjects; and analysis of variance was used to compare the
GMC changes in different time points after MMR vaccination. Results: Among 4 190
children, 2 280 were males (54.42%) and 1 910 were females(45.58%), and the
positive rate of IgG antibody was 81.38% (3 344). There were 3 156 (95.18%)
children vaccinated with one dose MMR, 187 (4.80%) children with two dose MMR,
and 1 (0.02%) child with three dose MMR. The difference in positive rate of IgG
antibody among different aged subjects showed statistical significance
(chi(2)=58.61, P<0.001), the highest positive rate was in group of subjects aged
4-5 years old, at 89.43% (406/454), while the lowest positive rate was found
among subjects aged 6-7 years old, at 75.63% (1 648/2 179). The positive rate
after one dose of MMR vaccination was 79.14% (3 156/3 988), significantly less
than it after two doses (93.03%, 187/201) (chi(2)=22.93, P<0.001). The GMC level
at years<1, 1-<2, 2-<3, 3-<4, >=4 following one dose MMR in the 3 988 children
was 152.47, 227.78, 167.08, 126.91, 79.43 mU/ml, whose difference was
statistically significant (F=51.29, P<0.001). Conclusion: The sero-prevalence of
IgG antibody in the children aged 2-7 years old in Jiangsu province was high. The
positive rate among who received two doses MMR was significantly higher than it
among who received just one dose, and the GMC level waned with times.
PMID- 28693083
TI - [Influence of growing experience on non-heterosexual orientation among male
college students in Nanjing].
AB - Objective: To analyze the influence of growing experience on non-heterosexual
orientation among male college students. Methods: From October to November in
2015, a total of 2 535 male students from 96 classes in 14 colleges/departments
were recruited from two colleges that participated in the experimental work of
AIDS prevention by cluster random sampling method. A structured questionnaire was
administered in this study, including general demographic information, growing
experience and Kinsey scale (to evaluate sexual orientation). Out of 2 500
questionnaires distributed in this study, 2 332 effective copies were withdrew,
with the effective rate at 93.3%. Chi square test was used to analyze the
differences of non-heterosexual orientation among the individuals with different
social demographic characteristics. Multivariate logistic regression model was
used to analyze the influencing factors of non-heterosexual orientation. Results:
Among the 2 332 individuals, the proportion of self-reported non-heterosexual was
6.2% (144).The proportions of male students who identify as non-heterosexual from
freshman to junior year were 5.2%(63/1216),6.9%(65/941),11.7%(13/111) and
4.7%(3/64), respectively (chi(2)=9.06,P=0.029). Compared with the individuals of
very good relationship with parents, those with bad relationship (OR=3.3, 95%CI:
1.7-6.5) and general relationship (OR=1.7, 95%CI: 1.0-2.9) with parents had a
higher risk of non-heterosexual orientation, respectively. Those encountered
sexual assault had a higher risk of non-heterosexual orientation than those
without encountered sexual assault (OR=5.9, 95%CI: 3.2-10.9). Conclusions: This
study reported a high proportion of self-reported non-heterosexual among college
male students in Nanjing, and highlighted the importance of targeting students
with poor parental relationships and who subjected to sexually abused.
PMID- 28693084
TI - [Survey of HIV-1 drug resistance threshold in Shandong Province in 2013-2015].
AB - Objective: To survey the prevalence of drug resistant HIV-1 in Shandong province
in 2013-2015. Methods: WHO truncated sequential sampling technique was adopted by
using 77 and 53 samples of newly diagnosed as HIV-1 positive and aged 16-25 years
in Shandong province in 2013 and 2015. RNA was prepared and HIV-1 pol region was
amplified by RT-PCR and nested PCR. Pol genetic mutation associated with drug
resistance was analyzed. Results: The success rates for sequence acquisition of
the survey were 100% (77/77) and 94% (50/53) in 2013 and 2015, and the main
subtype was CRF01_AE. A total of 2 surveillance drug-resistance mutation(SDRMs)
and 3 SDRMs were found by analyzing the 47 sequences each year, sampled in 2013
and 2015, indicating that the prevalence of drug resistant HIV-1 stains was low
in 2013, and moderate in 2015. A total of 5 individuals with drug resistant HIV-1
stains found in this study were mainly infected by homosexual transmission (3
cases), and the other two samples were different: one was infected by
heterosexual transmission, the other was infected by IDU. The subtype was
CRF01_AE (2 cases) , CRF07_BC (2 cases) and B (1 case) . SDRMs for protease
inhibitor (PIs), nucleotide HIV-reverse transcriptase inhibitor (NRTIs) and non
NRTI (NNRTIs) were all found in the individuals with drug resistant HIV-1 stains.
Conclusion: CRF01_AE were the main HIV-1 subtypes of recently reported HIV
infected individuals in Shandong province, and the HIV-1 drug resistant strains
transmission was catalogued as at low and moderate prevalence level in 2013 and
2015.
PMID- 28693085
TI - [Molecular characterization genetic diversity of extended-spectrum beta
lactamases-harboring conjugative plasmids identified in multi-drug resistant
Escherichia coli isolated from food in China].
AB - Objective: The purpose of this study was to investigate the molecular
characteristics of ESBL-encoding conjugative plasmid identified in muti-drug
resistant Escherichia coli isolated from food. Methods: 465 Escherichia coli
isolates were collected from national foodborne disease surveillance net from
2013 to 2014 (salad, n=159; meat, n=102; processed meat, n=95; cakes/rice, n=46;
cooked dish, n=63). ESBLs strain was detected by Mueller-Hinton agar plate, and
then its drug resistance was tested by agar dilution method. Polymerase chain
reaction (PCR) and DNA sequencing were performed to identify the corresponding
ESBL genes. Plasmids were typed by PCR-based replicon typing and their
characteristics were determined by S1-nuclease pulsed-field gel electrophoresis
method. Broth mating assays were carried out for all isolates to determine
whether the ESBL marker could be transferred by conjugation. Results: 12 E. coli
were found to be resistant to cefotaxime, and all of which were confirmed as
ESBLs. The 12 isolates all carried different types of CTX-M genes resistant to
drug, and 7 of which carried TEM type as well. All 12 isolates contained at least
one plasmid and some had four plasmids, with size ranging from 47-to 220-kb by S1
PFGE anaylsis. Seven isolates demonstrated the ability to transfer their
cefotaxime resistance marker to the recotper strain J53 by only one plasmid.
Conclusion: This study highlights the diversity of the multi-drug resistant E.
coli and also the diversity of ESBL genes in China. Plasmids carrying these genes
poses a serious threat to food safety in China.
PMID- 28693086
TI - [Study of the effect of occupational exposure to glyphosate on hepatorenal
function].
AB - Objective: To explore the effect of occupational exposure to glyphosate on
hepatorenal function. Methods: 526 workers who were occupationally exposed to
glyphosate from 5 glyphosate-producing factories were selected as cases; and
another 442 administrative staffs who were not exposed to glyphosate were
selected as controls from April to November, 2014. All the subjects accepted
occupational health examination. The concentration level of glyphosate in the air
of workshop was detected and the time weighted average concentration (TWA) was
calculated. And analyze the difference of hepatorenal fuction between case group
and control group. Result: The age of the subjects in the case and control groups
were separately (35.6+/-10.3), (34.3+/-9.7) years old, with the length of working
for (6.5+/-5.7), (7.7+/-6.8) years. The TWA of glyphosate in the case group was
between <0.03-48.91 mg/m(3), with the geometric mean at 3.78 mg/m(3). The overall
rates of abnormal hepatic and renal function in the case group were 14.4% (76
cases) and 16.2% (85 cases), respectively; while those were 5.0% (22 cases) and
4.8% (21 cases), respectively in control group, and the difference showed
statistical significance (P<0.05). When TWA reached <0.03-6.00 mg/m(3), the
difference of hepatorenal fuction between case group and control group showed
statistical significance, and the rates of abnormal hepatic and renal function
was 8.0% (36/447) and 9.8% (44/447) respectively in case group. When cumulative
exposure level reached <1.56-68.64 g, the difference of hepatorenal fuction
between case group and control group showed statistical significance, and the
rates increased to 9.2% (37/404) and 10.4% (42/404) respectively in group of
cases. Conclusion: Glyphosate can affect the hepatic and renal function among
occupational exposure population, and there was an association between the effect
and the exposure dose.
PMID- 28693087
TI - [Quantitative structure-activity relationship prediction of carcinogenicity of N
nitroso compounds based on category approach and read-across].
AB - Objective: New quantitative structure-activity relationship (QSAR) method was
used to predict N-nitroso compounds (NOCs) carcinogenicity. This could provide
evidences for health risk assessment of the chemicals. Methods: Total 74 chemical
substances of NOCs were included as target chemicals for this validation study by
using QSAR Toolbox based on category approach and read-across. The included 74
NOCs were categorized and subcategorized respectively using "Organic functional
groups, Norbert Haider " profiler and "DNA binding by OASIS V.1.1" profiler.
Carcinogenicity of rat were used as target of prediction, the carcinogenicity
results: of analogues in chemical categories were cross-read to obtain the
carcinogenic predictive results of the target chemicals. Results 74 NOCs included
26 nonclic N-nitrosamines, 24 cyclic N-nitrosamines and 24 N-nitrosamides The
sensitivity, specificity and concordance of the category approach and read-across
for predicting carcinogenicity of 74 NOCs were 75% (48/64), 70%(7/10) and 74%
(55/74) respectively. The concordance for noncyclic N-nitrosamines, cyclic N
nitrosamines and N-nitrosamides were 88% (23/26), 71% (17/24) and 63% (15/24)
respectively. Conclusion: QSAR based on category approach and read-across is good
for prediction of NOCs carcinogenicity, and can be used for high-throughput
qualitative prediction of NOCs carcinogenicity.
PMID- 28693088
TI - [Study of the relevant factors of behavioral development among 30-month-old
infants in rural area of Shaanxi Province].
AB - Objective: To explore the relevant factors of behavioral development among 30
month-old infants in rural area, Shaanxi Province. Methods: The behavioral
development among 977 infants aged 30-month-old was evaluated in Changwu and
Binxian of Shaanxi province from July 2006 to August 2008. The inclusion criteria
included single live birth between January 2004 and February 2006, mother had
participated in a community-based intervention study named "Impact of multi
micronutrient supplementation during pregnancy on low birth weight and premature
delivery" . Infants who had obvious deformity or other birth defects, infants who
could not complete the questionnaire survey, physical examination were excluded
from the study. The self-designed questionnaire was used to investigate the
information of feeding patterns, disease status, physical development, and
immunization status of the infants, and their behavioral development were
assessed by Bayley scales of infant development (BSID). General Linear Model was
used to adjust the possible confounding factors, and the analysis of variance was
performed to explore the effects on the behavioral development among infants aged
30-month-old. Results: Among the infants in the study, the average age was
(30.6+/-0.6) months old, the mean birth weight was (3 199.1+/-405.9)g. After
adjusted the mothers' age of delivery, educational level and occupation of the
parents, family ecnomic conditions and the number of children, infants whose
mother exposed to toxic chemicals during pregnancy had lower score in activity (
0.179+/-0.961) and lower score in concentration (-0.177+/-1.099) compared with
infants with unexposed mother (0.058+/-1.006, P=0.001; 0.057+/-0.960, P=0.003).
Similarly, infants whose mother took drugs during pregnancy had lower score in
persistent behaviors (-0.070+/-1.000) compared with infants whose mother did
not(0.085+/-1.006, P=0.017). Compared with normal birth infants(0.043+/-0.981,
P=0.007; 0.021+/-0.984, P=0.034), infants less than gestational age and low birth
weight had lower score in concentration(-0.198+/-1.063 and-0.389+/-1.285,
respectively). After adjusted the delivery gestational age of mothers, the months
of infants, the mothers' age of delivery, educational level and occupation of the
parents, family ecnomic conditions, the number of children, and the main
orderlies of infants, the score of activity of infants suffered from diseases in
early month age was-0.049+/-0.992, which was lower than those who did not(0.207+/
1.011, P=0.001). The infants with Rickets signs had lower score in motor
coordination (-0.218+/-0.896) than normal infants (0.031+/-1.011, P=0.013).
Infants whose mother with adequate micronutrient supplementation in pregnancy had
higher score in concentration (0.066+/-0.966) than those whose mother with
insufficient supplementation (-0.062+/-1.027, P=0.043). Furthermore, infants with
fine protein added and minerals and vitamins added had higher score in activity
and concentration compared with those insufficient, who scored 0.078+/-1.013 and
0.496+/-0.872 (-0.254+/-0.924, P<0.001; 0.001+/-0.997, P=0.033), respectively.
Conclusion: Micronutrient supplementation during pregnancy and reasonable
nutrition added during childhood could affect behavioral development among
infants.
PMID- 28693089
TI - [Effect of genetic polymorphisms on change in body mass index and obesity status
during childhood].
AB - Objective: The present study aimed to prospectively validate whether the single
nucleotide polymorphisms (SNPs) in obesity-related genes were associated with
change in body mass index (BMI) and obesity status during childhood. Methods:
Based on the Beijing Child and Adolescent Metabolic Syndrome study (BCAMS), which
was initiated between April and October in 2004, we conducted a follow-up study
among 1 624 children aged 6 to 11 years old with genetic data in December 2010. A
total of 777 children (246 obese and 531 non-obese) were reassessed for BMI. Z
score of BMI was used to standardize for age and sex. The changes in BMI Z-score
during follow up were calcnlated SNPs were genotyped by quantitative Real-time
PCR (rs9939609, rs6499640, rs7138803, rs1805081, rs17782313, rs6265, rs10938397,
rs6235, rs29941, rs2844479, rs10913469 and rs4788102). Overweight and obesity
were diagnosed by the age-and sex-specific BMI cutoffs recommended by the
International Obesity Task Force. A multilocus genetic risk score for BMI was
calculated as the simple sum of alleles of all the SNPs associated with BMI.
Linear regression models and logistic regression models were performed to assess
the associations of change in BMI Z-score and obese status with genotypes
(assuming an additive model), respectively. Results: During 6 years of follow-up,
158 previously obese children remained obese as they aged into adolescence, and
88 transiently obese children were not obese during the second survey, 58
children were newly identified obese, and the other 473 children remained their
non-obese state. BMI Z-score increased from 1.41+/-0.05 at baseline to 1.57+/
0.06 at follow up.The genotypes of the SNPs except rs6499640(P=0.033) and
rs6265(P=0.041) were in Hardy-Weinberg equilibrium in each group (P>0.05). Each
additional copy of the rs9939609 A allele was significantly associated with an
increase in BMI Z-score (beta=0.205, P=0.014) during follow up. Per C allele of
rs17782313 was associated with an increase in BMI Z-score at baseline
(beta=0.268, P=0.003). As the non-obese reference, a significantly relative risk
of obesity at follow up was observed for children carrying rs9939609 A-allele
versus the T-allele carriers (OR=2.37, 95%CI: 1.45-3.88, P=0.001). Rs17782313 C
allele was significantly increase the risk of obesity only at baseline (OR=1.79,
95%CI: 1.24-2.60, P=0.002). Rs1805081 A-allele was significantly associated with
durative of obesity (OR=1.45, 95%CI: 1.04-2.03, P=0.028). Each unit higher
genetic risk score was associated with increases risk of 0.18 times (OR=1.18,
95%CI: 1.05-1.33) in childhood transient obesity, and 0.22 times (OR=1.22, 95%
CI: 1.06-1.42) in incident obesity at follow-up. But it was not significantly
associated with persisted obesity during 6 years of follow-up (OR=1.09, 95% CI:
0.99-1.20). Conclusion: We confirmed that the change of BMI and obesity status in
children was affected by different genetic factors. Individual who carries more
risk alleles in obesity-related genes may increase the susceptibility to obesity.
PMID- 28693090
TI - [Study of Basal metabolic rate of 81 young adults aged 20-29 years old in
Changsha].
AB - Objective: To determine the basal metabolic rate (BMR) of young adults aged
between 20-29 years old in Changsha. Methods: We recruited volunteers to join in
our research project from April to May, 2015. All recruited volunteers must meet
the inclusion criteria: aged 20-29 years old, height between 164-180 centimeters
in males and 154-167 centimeters in females, in good health condition, and with
no habit of regular physical exercise in last year. Finally, 81 qualified
volunteers were selected as research objects, including 43 males and 38 females.
The BMR, resting lying metabolism rate and resting sitting metabolism rate of the
subjects were detected, and the determined BMR was compared with the calculated
results: from the adjusted Schofield equation. Results The BMR, resting lying
metabolism rate and resting sitting metabolism rate among males were (166.10+/
22.09), (174.22+/-24.56), and (179.54+/-23.35) kJ.m(-2).h(-1), respectively,
which were all higher than those among females were (137.70+/-20.04), (149.79+/
19.25), and (167.78+/-26.02) kJ.m(-2).h(-1), respectively, (P<0.001). The BMR of
males and females calculated from the adjusted Schofield equation were (160.83+/
3.93), and (140.29+/-4.18) kJ.m(-2).h(-1), respectively, and there was no
significantly statistical difference found between the determined BMR and the
calculated results from Schofield equation (adjusted) classified by sex, all P
values >0.05. Conclusion: The BMR of young adults aged 20-29 years old in
Changsha was in the national average level, and the adjusted Schofield equation
displayed fine accuracy in predicting BMR of young adults aged 20-29 years old in
Changsha.
PMID- 28693091
TI - [Etiology characteristics analysis of the first input human infection of avian
influenza H7N9 in Tianjin].
PMID- 28693092
TI - [Epidemic and molecular characteristic of human adenovirus infection among
patients with febrile respiratory syndrome from a hospital in Qinghai Province,
2012-2015].
PMID- 28693093
TI - [HIV prevalence and its high risk behaviors among Myanmar populations living in
Dehong prefecture, Yunnan Province].
PMID- 28693094
TI - [Review on the evaluation research of the effects of smoke-free legislations on
cardiovascular diseases].
AB - A substantial amount of data suggested that exposure to secondhand smoke (SHS)
could cause cardiovascular diseases and acute coronary events in nonsmoking
adults. In order to protect the public from SHS, more and more countries and
regions across the world have enacted and implemented smoke-free legislations.
Developed countries, such as USA, Canada, the Great Britain, Ireland, Italy and
Spain, have carried out many studies to analyze the effects of smoke-free
legislations on the hospital admission, incidence and mortality of cardiovascular
diseases with the purpose of confirming the health benefits of the smoking ban
and promoting the conduct of the ban. We searched PubMed, EMBASE, Web of Science,
Cochrane Library,China National Knowledge Infrastructure(CNKI),WANFANG databaseto
summarize the study designs, evaluating indicators, statistical methods and
results of these studies to provide reference for evaluating smoke-free
legislations in inland cities in China.
PMID- 28693095
TI - Analysis of NSP4 Gene and Its Association with Genotyping of Rotavirus Group A in
Stool Samples
AB - Background: Non-structural protein 4 (NSP4) is a critical protein for rotavirus
(RV) replication and assembly. This protein has multiple domains and motifs that
predispose its function and activity. NSP4 has a sequence divergence in human and
animal RVs. Recently, 14 genotypes (E1-E14) of NSP4 have been identified, and E1
and E2 have been shown to be the most common genotypes in human. Methods: The
gene and protein sequence of NSP4 in RV-positive samples were inspected with the
aim of NSP4 genotyping and variation analysis in viroporin and other domains. P
and G typings of RV samples were carried out by WHO primers using a semi
multiplex PCR method. Non-typeable RV samples were amplified by conserved primers
and sequenced. Results: In viroporin and enterotoxin, conserved sequence was
detected, and amino acids substitution with the same biochemical properties was
found. Conclusion: Association of NSP4 genotype with P or G genotyping G1/G9
correlates with E1 genogroups. In electrophoretyping of RV, E2 genotype had a
short pattern when compared to E1.
PMID- 28693096
TI - Chiral penicillamine-modified selenium nanoparticles enantioselectively inhibit
metal-induced amyloid beta aggregation for treating Alzheimer's disease.
AB - Nanometer-scale chirality has gained significant interest from different research
fields due to its fundamental importance in nature and living matter. In this
study, we design and synthesize chiral penicillamine-capped selenium
nanoparticles (l-/d-Pen@Se NPs) that can act as a novel class of chiral amyloid
beta (Abeta) inhibitors. In this work, d-Pen@Se NPs demonstrate higher inhibition
efficiency, as well as ameliorate cognition and memory impairments. We used rat
pheochromocytoma (PC12) cells to perform real-time cell analysis assay (RTCA) to
probe the potential cytotoxicity of l-/d-Pen@Se NPs. At any given time point, the
cell index decreases as d-Pen@Se NPs concentration increases, demonstrating a
concentration-dependent cytotoxic effect on PC12 cells. In addition, d-Pen@Se NPs
also reduced Zn2+-induced intracellular Abeta40 fibrillation, while l-Pen@Se NPs
did not. The histological analysis demonstrates that mice treated with d-Pen@Se
NPs did not exhibit signs of in vivo systemic toxicity in major organs. Our
findings are highly encouraging in terms of providing substantial evidence of the
safety of chiral d-Pen@Se NPs for biomedical application. We expect that these
results will be relevant for other chiral NPs for treatment of Alzheimer's
disease and have broad implications in NP-based studies and applications.
PMID- 28693097
TI - Graphene-like carbon nitride nanosheet as a novel sensing platform for
electrochemical determination of tryptophan.
AB - In this paper, a new and facile strategy has been demonstrated for the
electrochemical determination of tryptophan (Trp), based on graphite-like carbon
nitride (g-C3N4) nanosheets modified glassy carbon (CNNS/GC) electrode. The g
C3N4 nanosheets were obtained via exfoliating bulk graphitic carbon nitride (bg
C3N4), which was synthesized using a thermal poly-condensation process. The
obtained g-C3N4 nanosheets were characterized by X-ray diffraction (XRD),
transmission electron microscopy (TEM), Fourier transform infrared (FTIR)
spectroscopy and atomic force microscopy (AFM). The results confirmed graphite
like structure with thickness of about 6-8nm. The as-synthesized g-C3N4
nanosheets were closely attached to the surface of GC electrode to construct
electrochemical sensor without needing any film-forming agents. The CNNS/GC
electrode exhibited good electrocatalytic activity towards Trp, and hereby some
parameters, including scan rate and pH effect on Trp determination were
investigated. Under the optimum experimental conditions, the oxidation peak
currents had good linear relationship with Trp concentrations in the range of 0.1
110MUM and a detection limit of 0.024MUM (S/N=3) was achieved. In addition, the
obtained sensor showed good sensitivity, favorable repeatability, and long-term
stability. Finally, the proposed electrochemical sensor has been successfully
applied for the determination of Trp concentration in real samples with
satisfactory results.
PMID- 28693098
TI - Iminodiacetic acid-conjugated nanoparticles as a bifunctional modulator against
Zn2+-mediated amyloid beta-protein aggregation and cytotoxicity.
AB - Alzheimer's disease is characterized by the accumulation of amyloid beta-protein
(Abeta) fibrils in human brain, and the binding of metal ions, such as Zn2+, is
closely associated with the aggregation and cytotoxicity of Abeta. Here, we
designed and synthesized iminodiacetic acid-conjugated nanoparticles (IDA-NP) to
modulate Abeta42 aggregation and reduce the cytotoxicity accelerated by Zn2+.
Results showed that IDA-NP enabled high metal-chelate capacity (752MUmol/g) and
potent inhibition capability against Abeta42 fibrillation. Zn2+ ions could be
completely removed by chelating to IDA-NP, which leads to the recovery of on
pathway Abeta42 fibrillation. Then, the special surface character of IDA-NP
inhibited Abeta42 fibrillation. As a result, IDA-NP protected SH-SY5Y cells from
the cytotoxicity induced by Zn2+-Abeta42 species, as evidenced by about 80% (from
47.6% to 86.3%) increase of the cell viability. The research proved that IDA-NP
was a potent bifunctional nano-modulator for preventing Zn2+-mediated Abeta
aggregation and cytotoxicity.
PMID- 28693099
TI - Self-assembled three-dimensional Pd/MoS2/reduced graphene oxide nanocatalyst: A
case for homogeneous leaching mechanism.
AB - In this work, a new design of three-dimensional (3D) molybdenum disulfide
reduced graphene oxide nanosheets supported palladium (Pd/MoS2-rGO) catalyst was
prepared by a facile one-pot self-assembled procedure. The existence of MoS2 not
only succeeded in preventing the restacking of rGO nanosheets and increasing the
specific surface area, but also afforded an additional transport platform for Pd
nanoparticles to facilitate its catalytic properties. Because of the specific
structural and different functional components, the as-prepared Pd/MoS2-rGO
showed superior catalytic performance and reusability towards the cross-coupling
reactions and the reduction of 4-nitrophenol. Moreover, it was confirmed that the
catalytic nature of Pd catalyst is a kind of similar homogeneous leaching
mechanism with the hot filtration test, the solid-phase poisoning and the three
phase test, etc. This means that leaching of soluble Pd species promotes the
reaction process in the liquid phase, and the leaching Pd can return to the
carrier of catalyst after completion of transformation. Therefore, the rational
design of 3D MoS2-rGO hydrogel material supported highly active Pd nanoparticles,
combined with a facile one-pot self-assembled procedure, provides a universal
strategy to construct desirable 3D multifunctional nanocatalysts that can be used
to research the catalytic nature of active Pd.
PMID- 28693100
TI - A contact angle hysteresis model based on the fractal structure of contact line.
AB - Contact angle is one of the most popular concept used in fields such as wetting,
transport and microfludics. In practice, different contact angles such as
equilibrium, receding and advancing contact angles are observed due to
hysteresis. The connection among these contact angles is important in revealing
the chemical and physical properties of surfaces related to wetting. Inspired by
the fractal structure of contact line, we propose a single parameter model
depicting the connection of the three angles. This parameter is decided by the
fractal structure of the contact line. The results of this model agree with
experimental observations. In certain cases, it can be reduced to other existing
models. It also provides a new point of view in understanding the physical nature
of the contact angle hysteresis. Interestingly, some counter-intuitive phenomena,
such as the binary receding angles, are indicated in this model, which are waited
to be validated by experiments.
PMID- 28693101
TI - Monitoring alkylphenols in water using the polar organic chemical integrative
sampler (POCIS): Determining sampling rates via the extraction of PES membranes
and Oasis beads.
AB - Polar organic chemical integrative samplers (POCIS) have previously been used to
monitor alkylphenol (AP) contamination in water and produced water. However, only
the sorbent receiving phase of the POCIS (Oasis beads) is traditionally analyzed,
thus limiting the use of POCIS for monitoring a range of APs with varying
hydrophobicity. Here a "pharmaceutical" POCIS was calibrated in the laboratory
using a static renewal setup for APs (from 2-ethylphenol to 4-n-nonylphenol) with
varying hydrophobicity (log Kow between 2.47 and 5.76). The POCIS sampler was
calibrated over its 28 day integrative regime and sampling rates (Rs) were
determined. Uptake was shown to be a function of AP hydrophobicity where
compounds with log Kow < 4 were preferentially accumulated in Oasis beads, and
compounds with log Kow > 5 were preferentially accumulated in the PES membranes.
A lag phase (over a 24 h period) before uptake in to the PES membranes occurred
was evident. This work demonstrates that the analysis of both POCIS phases is
vital in order to correctly determine environmentally relevant concentrations
owing to the fact that for APs with log Kow <= 4 uptake, to the PES membranes and
the Oasis beads, involves different processes compared to APs with log Kow >= 4.
The extraction of both the POCIS matrices is thus recommended in order to assess
the concentration of hydrophobic APs (log Kow >= 4), as well as hydrophilic APs,
most effectively.
PMID- 28693102
TI - Chemically deposited Bi2S3:PbS solid solution thin film as supercapacitive
electrode.
AB - Low-cost, easily synthesized, and high energy/power density embedded stable
supercapacitive electrodes are the demands for today's renewable and green energy
dependent generation. In search of that, Bi2S3:PbS solid solution in thin film
form has been synthesized by modest successive ionic layer adsorption and
reaction (SILAR) method and characterized by XRD, FESEM, and HRTEM. Formation of
solid solution in the form of nanoparticles gilded thin film exposes sufficient
electroactive cavities for electroactive ions to incorporate. The composite
exhibited excellent specific capacitance of 402.4F/g at current density of
1mA/cm2 with modest charge-discharge cycles. In terms of energy storage, it
exhibited maximum specific power of 20.1Wh/kg with accepting specific power of
1.2kW/kg. The combination of two nanoparticles in nanocomposites thin film
supplies new tactic for energy storage applications.
PMID- 28693103
TI - Functionalized magnetic iron oxide/polyacrylonitrile composite electrospun fibers
as effective chromium (VI) adsorbents for water purification.
AB - Inorganic/organic composite electrospun fibers have been extensively investigated
as adsorbents for the wastewater treatment. In this study, branched
polyethylenimine (b-PEI) functionalized magnetic iron oxide
(Fe3O4)/polyacrylonitrile (PAN) composite electrospun fiber adsorbent (b-PEI
FePAN) was fabricated and systematically explored for the removal of toxic
hexavalent chromium [Cr(VI)]. b-PEI grafted PAN organic component not only acted
as the flexible substrate to load Fe3O4 particles but also made a contribution to
the improved adsorption capacity. In the batch adsorption test, the maximum
adsorption capacity based on Langmuir fitting was 684.93mg/g, which was higher
than most of the reported adsorbents. The removal efficiency could reach above
98% with a dosage of 0.5mg/mL in the real water samples. Moreover, the filtration
efficiency was also above 98.5% even at a high flux of 765L.m-2.h-1 in dynamic
filtration experiment. According to mechanism analysis, both electrostatic
adsorption and reduction action were involved in the Cr(VI) removal processes.
These results demonstrate that b-PEI functionalized Fe3O4/PAN composite
electrospun fibers have promising potential in water purification field.
PMID- 28693104
TI - New insight into the distribution pattern, levels, and risk diagnosis of FRs in
indoor and outdoor air at low- and high-altitude zones of Pakistan: Implications
for sources and exposure.
AB - Data regarding flame retardants (FRs) in indoor and outdoor air and their
exposure to population are scarce and especially unknown in the case of Pakistan.
The current study was designed to probe FR concentrations and distribution
pattern in indoor and outdoor air at different altitudinal zones (DAZs) of
Pakistan with special emphasis on their risk to the exposed population. In this
study, passive air samplers for the purpose of FR deposition were deployed in
indoor and outdoor air at the industrial, rural, and background/colder
zones/sites. All the indoor and outdoor air samples collected from DAZs were
analyzed for the target FRs (9.30-472.30 pg/m3), showing a decreasing trend as
follows: ?NBFRs > ?PBDEs > ?DP. However, significant correlations among FRs in
the indoor and outdoor air at DAZs signified a similar source of FR origin that
is used in different consumer goods. Furthermore, air mass trajectories revealed
that movement of air over industrial area sources influenced concentrations of
FRs at rural sites. The FR concentrations, estimated daily intake (EDI) and the
hazard quotient (HQ), were recorded to be higher in toddlers than those in
adults. In addition, indoor air samples showed higher FR levels, EDI and HQ, than
outdoor air samples. An elevated FR concentrations and their prevalent exposure
risks were recorded in the industrial zones followed by rural and background
zones. The HQ for BDE-47 and BDE-99 in the indoor and outdoor air samples at
different industrial and rural sites were recorded to be >1 in toddlers and
adults, this further warrants a health risk in the population. However, FR
investigation in indoor and outdoor air samples will provide a baseline data in
Pakistan to take further steps by the government and agencies for its
implementations.
PMID- 28693105
TI - Path analysis of prenatal mercury levels and birth weights in Korean and
Taiwanese birth cohorts.
AB - Prospective cohort studies of the effect of mercury (Hg) exposure on birth weight
have shown conflicting results. We combined data from Taiwanese and Korean birth
cohorts, and assessed the effects of Hg exposure on birth weight. The first
cohort was drawn from the Mothers and Children's Environmental Health (MOCEH)
study performed in Korea from 2006 to 2010. The second cohort was enrolled from
2004 to 2005 and included singleton term births from the Taiwan Birth Panel Study
(TBPS). In total, 1147 pregnant women were included in this study. A pooled
analysis was performed to obtain combined estimates of the association between
prenatal total Hg exposure and birth weight. A significant negative association
between maternal and cord blood Hg and birth weight in the high-Hg group (Hg
level>25th percentile) was detected (maternal blood: beta=-0.056; 95% CI, -0.100
to -0.013, cord blood: beta=-0.075; 95% CI, -0.121 to -0.028). Hg level showed a
negative coefficient in the path analysis, indicating an adverse effect on birth
weight (total effects: beta=-0.177, P=0.01 in MOCEH, beta=-0.204, P=0.03 in
TBPS), but fish consumption exhibited a strong positive coefficient. In addition,
fish consumption exerted a significant indirect effect on birth weight through
exposure to cord blood Hg. Exposure to hazardous contaminants and beneficial
nutrients may be highly correlated in those who frequently consume fish.
Moreover, Hg in cord blood may adversely affect birth weight.
PMID- 28693106
TI - Polycyclic aromatic hydrocarbons contamination in surface soil of China: A
review.
AB - This paper reviews the concentration, distribution, source, and potential risk of
polycyclic aromatic hydrocarbons (PAHs) in surface soils of China through
analysis of data from >6000 surface soil samples in nearly 100 references. The
mean value of total 16 PAHs was 730ng.g-1 in surface soil in China, a relatively
lower or moderate level than other countries. Based on the Maliszewska-Kordybach
classification criteria, the proportions of heavily contaminated, contaminated,
weakly contaminated, and non-contaminated soil samples were 21.4%, 11.9%, 49.5%,
and 17.2%, respectively. There was a clear geographical distribution, with
concentrations of the total 16 PAHs descending in the following order: Northeast
China (1467ng.g-1)>North China (911ng.g-1)>East China (737ng.g-1)>South China
(349ng.g-1)>West China (209ng.g-1). Moreover, it was found that the PAH
concentrations in surface soil in China descended along the urban-suburban-rural
gradient. The concentration and distribution of PAHs were mainly related to the
degree of economic development, population density, climatic conditions, and soil
organic matter, and the divergence of regional economic patterns and climatic
conditions was the main reason for the observed PAH distribution in the soils.
Traffic emissions, coal and biomass combustion mainly contributed to the PAH
contamination of surface soil in China during the process of urbanization and
industrialization, and the average Benzo(a)pyrene equivalent concentration of
?PAH7c (seven carcinogenic PAHs) was 99ng.g-1, which indicated the soil samples
had a small potential carcinogenic risk. Despite soil pollution being generally
low, PAH concentrations in some areas were relatively high, therefore it is
necessary to produce strategies, such as establishing effective guidelines and
developing environmental-friendly technology to reduce PAH emissions, and prevent
further contamination.
PMID- 28693107
TI - Using ecosystem engineers as tools in habitat restoration and rewilding: beaver
and wetlands.
AB - Potential for habitat restoration is increasingly used as an argument for
reintroducing ecosystem engineers. Beaver have well known effects on
hydromorphology through dam construction, but their scope to restore wetland
biodiversity in areas degraded by agriculture is largely inferred. Our study
presents the first formal monitoring of a planned beaver-assisted restoration,
focussing on changes in vegetation over 12years within an agriculturally-degraded
fen following beaver release, based on repeated sampling of fixed plots. Effects
are compared to ungrazed exclosures which allowed the wider influence of
waterlogging to be separated from disturbance through tree felling and herbivory.
After 12years of beaver presence mean plant species richness had increased on
average by 46% per plot, whilst the cumulative number of species recorded
increased on average by 148%. Heterogeneity, measured by dissimilarity of plot
composition, increased on average by 71%. Plants associated with high moisture
and light conditions increased significantly in coverage, whereas species
indicative of high nitrogen decreased. Areas exposed to both grazing and
waterlogging generally showed the most pronounced change in composition, with
effects of grazing seemingly additive, but secondary, to those of waterlogging.
Our study illustrates that a well-known ecosystem engineer, the beaver, can with
time transform agricultural land into a comparatively species-rich and
heterogeneous wetland environment, thus meeting common restoration objectives.
This offers a passive but innovative solution to the problems of wetland habitat
loss that complements the value of beavers for water or sediment storage and flow
attenuation. The role of larger herbivores has been significantly overlooked in
our understanding of freshwater ecosystem function; the use of such species may
yet emerge as the missing ingredient in successful restoration.
PMID- 28693108
TI - Nitrate release from waste rock dumps in the Elk Valley, British Columbia,
Canada.
AB - The origin, distribution and leaching of nitrate (NO3-) from coal waste rock
dumps in the Elk Valley, British Columbia, Canada were defined using chemical and
NO3- isotope analyses (delta15N- and delta18O-NO3-) of solids samples of pre- and
post-blast waste rock and from thick (up to 180m) unsaturated waste rock dump
profiles constructed between 1982 and 2012 as well as water samples collected
from a rock drain located at the base of one dump and effluent from humidity cell
(HC) and leach pad (LP) tests on waste rock. delta15N- and delta18O-NO3- values
and NO3- concentrations of waste rock and rock drain waters confirmed the source
of NO3- in the waste rock to be explosives and that limited to no denitrification
occurs in the dump. The average mass of N released during blasting was estimated
to be about 3-6% of the N in the explosives. NO3- concentrations in the fresh
blast waste rock and recently placed waste rock used for the HC and LP
experiments were highly variable, ranging from below detection to 241mg/kg. The
mean and median concentrations of these samples ranged from 10-30mg/kg. In this
range of concentrations, the initial aqueous concentration of fresh-blasted waste
rock could range from approximately 200-600mg NO3--N/L. Flushing of NO3- from the
HCs, LPs and a deep field profile was simulated using a scale dependent leaching
efficiency (f) where f ranged from 5-15% for HCs, to 35-80% for the LPs, to 80
90% for the field profile. Our findings show aqueous phase NO3- from blasting
residuals is present at highly variable initial concentrations in waste rock and
the majority of this NO3- (>75%) should be flushed by recharging water during
displacement of the first stored water volume.
PMID- 28693109
TI - Spatial and temporal distribution of urban heat islands.
AB - The formation of an urban heat island (UHI) is one of the most common impacts of
the urbanization process. To mitigate the effects of UHI, the planning of urban
forests (e.g., creation of parks, forests and afforestation streets) has been the
major tool applied in this context. Thus, the aim of this study is to evaluate
the spatial and temporal distribution of heat islands in Vila Velha, ES, Brazil
using the mono-window algorithm. The study followed these methodological steps:
1) mapping of urban green areas through a photointerpretation screen; 2)
application of the mono-window algorithm to obtain the spatial and temporal
patterns of land surface temperature (LST); 3) correlation between LST and the
normalized difference vegetation index (NDVI) and normalized difference build-up
index (NDBI); 4) application of ecological evaluation index. The results showed
that the mean values of LST in urban areas were at least 2.34 to 7.19 degrees C
higher than undeveloped areas. Moreover, the positive correlation between LST and
NDBI showed an amplifying effect of the developed areas for UHI, while areas with
a predominance of vegetation attenuated the effect of UHI. Urban centers,
clustered in some parts of the city, received the worst ecological assessment
index. Finally, the adoption of measures to guide the urban forest planning
within urban centers is necessary to mitigate the effect of heat islands and
provide thermal comfort in urban areas.
PMID- 28693110
TI - Potential effects of brevetoxins and toxic elements on various health variables
in Kemp's ridley (Lepidochelys kempii) and green (Chelonia mydas) sea turtles
after a red tide bloom event.
AB - Natural biotoxins and anthropogenic toxicants pose a significant risk to sea
turtle health. Documented effects of contaminants include potential disease
progression and adverse impacts on development, immune function, and survival in
these imperiled species. The shallow seagrass habitats of Florida's northwest
coast (Big Bend) serve as an important developmental habitat for Kemp's ridley
(Lepidochelys kempii) and green (Chelonia mydas) sea turtles; however, few
studies have been conducted in this area. Our objectives were (1) to evaluate
plasma analytes (mass, minimum straight carapace length, body condition index
[BCI], fibropapilloma tumor score, lysozyme, superoxide dismutase, reactive
oxygen/nitrogen species, plasma protein electrophoresis, cholesterol, and total
solids) in Kemp's ridleys and green turtles and their correlation to brevetoxins
that were released from a red tide bloom event from July-October 2014 in the Gulf
of Mexico near Florida's Big Bend, and (2) to analyze red blood cells in Kemp's
ridleys and green turtles for toxic elements (arsenic, cadmium, lead, mercury,
selenium, thallium) with correlation to the measured plasma analytes. Positive
correlations were observed between brevetoxins and alpha2-globulins in Kemp's
ridleys and alpha2- and gamma-globulins in green turtles, indicating potential
immunostimulation. Arsenic, cadmium, and lead positively correlated with
superoxide dismutase in Kemp's ridleys, suggesting oxidative stress. Lead and
mercury in green turtles negatively correlated with BCI, while mercury positively
correlated with total tumor score of green turtles afflicted with
fibropapillomatosis, suggesting a possible association with mercury and increased
tumor growth. The total tumor score of green turtles positively correlated with
total protein, total globulins, alpha2-globulins, and gamma-globulins, further
suggesting inflammation and immunomodulation as a result of fibropapillomatosis.
Lastly, brevetoxin concentrations were positively related to tumor score,
indicating potential tumor promotion by brevetoxin. These results signify that
brevetoxins and toxic elements elicit various negative effects on sea turtle
health, including immune function, oxidative stress, and possibly disease
progression.
PMID- 28693111
TI - Occurrence and spatial distribution of legacy and emerging organic pollutants in
marine sediments from the Atlantic coast (Andalusia, SW Spain).
AB - Contamination of aquatic systems by no longer used but very persistent compounds
(e.g., organochlorine pesticides) and newly detected chemicals, such as personal
care products (PCPs), represents a raising concern. In this study, we carried out
one of the first comparisons of both types of contaminants, legacy and emerging,
in two coastal systems (Cadiz Bay and Huelva Estuary). A wide range of analytes
were selected to this end, including hydrocarbons, UV filters, fragrances, and
antimicrobials. Analysis of surface sediments revealed the occurrence of 46 out
of 97 target analytes, most of them predominantly accumulated in depositional
areas with high organic carbon content. Polycyclic aromatic hydrocarbons (PAHs),
fragrances (e.g., octahydrotetramethyl acetophenone or "OTNE"), UV filters (e.g.,
octocrylene), and nonylphenol had the highest concentrations (up to 1098, 133.5,
72 and 575ngg-1, respectively). Several inputs were detected, from atmospheric
deposition after combustion to wastewater discharges and recreational activities.
However, an environmental risk assessment performed for those chemicals for which
ecotoxicological data were available, indicated that legacy compounds still pose
the highest potential risk towards benthonic organisms (individual hazard
quotients up to 580 for dichlorophenyldichloroethylene or "DDE") compared to
PCPs.
PMID- 28693112
TI - Association of prenatal passive smoking and metabolic gene polymorphisms with
child growth from birth to 3years of age in the Hokkaido Birth Cohort Study on
Environment and Children's Health.
AB - Although the effects of prenatal passive smoking on birth weight have been
reported, the effects of metabolic gene polymorphisms on passive smoking have not
been studied. Therefore, we investigated the effects of maternal passive smoking
and metabolic gene polymorphisms on child growth up to 3years of age using
cotinine as a biomarker. We included 1356 Japanese participants in a prospective
cohort between 2003 and 2007 (cotinine levels at the third trimester<=0.21ng/mL
and 0.22 to 11.48ng/mL for non-passive and passive smokers, respectively), and
measured child outcomes such as weight, length, head circumference, and Kaup
index. Additionally, we analyzed cytochrome P450 1A1 (CYP1A1), epoxide hydrolase
1 (EPHX1), and two N-acetyltransferase 2 (NAT2) genotypes using real-time
polymerase chain reaction methods. Associations were investigated using multiple
regression models. Kaup index gain from birth up to 3years of age was
significantly smaller in children born to passive smokers than in those born to
non-passive smokers (-0.34kg/m2; 95% confidence interval: -0.67, -0.01). Maternal
CYP1A1 genotype was not associated with prenatal passive smoking and Kaup index
gain, but was significantly associated with prenatal passive smoking and head
circumference gain from birth up to 3years of age (-0.75cm; 95% confidence
interval: -1.39, -0.12). Thus, this study suggests that prenatal passive smoking
may have potent effects on postnatal growth from birth up to 3years of age.
Moreover, children with maternal CYP1A1 genotype may be more susceptible to the
effects of prenatal passive smoking.
PMID- 28693113
TI - Multiple factors impact the contents of heavy metals in vegetables in high
natural background area of China.
AB - A field survey was conducted to investigate the concentrations of chromium (Cr),
nickel (Ni), copper (Cu), zinc (Zn), cadmium (Cd) and lead (Pb) in vegetables,
corresponding cultivated soils and irrigation waters from 36 open sites in high
natural background area of Wuzhou, South China. Redundancy analysis, Spearman's
rho correlation analysis and multiple regression analysis were adopted to
evaluate the contributions of impacting factors on metal contents in the edible
parts of vegetables. This study concluded that leafy and root vegetables had
relatively higher metal concentrations and adjusted transfer factor values
compared to fruiting vegetables according to nonparametric tests. Plant species,
total soil metal content and soil pH value were affirmed as three critical
factors with the highest contribution rate among all the influencing factors. The
bivariate curve equation models for heavy metals in the edible vegetable tissues
were well fitted to predict the metal concentrations in vegetables. The results
from this case study also suggested that it could be one of efficient strategies
for clean agricultural production and food safety in high natural background area
to breed vegetable varieties with low heavy metal accumulation and to enlarge
planting scale of these varieties.
PMID- 28693125
TI - Correction: Physiological characterization of a novel PPAR pan agonist, 2-(4-(5,6
methylenedioxybenzo[d]thiazol-2-yl)-2-methylphenoxy)-2-methylpropanoic acid
(MHY2013).
PMID- 28693126
TI - Correction: High-level expression of P21-Cdc/Rac-activated kinase 7 is closely
related to metastatic potential and poor prognosis of colon carcinoma.
PMID- 28693127
TI - The role of eukaryotic translation initiation factor 6 in tumors.
AB - Eukaryotic translation initiation factor 6 (eIF6) affects the maturation of 60S
ribosomal subunits. Found in yeast and mammalian cells, eIF6 is primarily located
in the cytoplasm of mammalian cells. Emerging evidence has demonstrated that the
dysregulated expression of eIF6 is important in several types of human cancer,
including head and neck carcinoma, colorectal cancer, non-small cell lung cancer
and ovarian serous adenocarcinoma. However, the molecular mechanisms by which
eIF6 functions during tumor formation and progression remain elusive. The present
review focuses on recent progress in terms of the mechanisms and functions of
eIF6 in human tumorigenesis or cancer cell lines, along with the signal
transduction pathways in which this novel translation initiation factor may
participate. Oncogenic Ras activates Notch-1 and promotes transcription of eIF6
via a recombining binding protein suppressor of Hairless-dependent mechanism. In
addition, overexpression of eIF6 results in aberrant activation of the Wnt/beta
catenin signaling pathway. Similarly, overexpressed eIF6 regulates its downstream
modulator, cell division control protein 42, which in turn affects oncogenesis.
Finally, the potential of eIF6 as a biomarker for diagnosis of cancer is also
discussed in the present review.
PMID- 28693128
TI - Pediatric haematopoiesis and related malignancies.
AB - Survival after acute paediatric (0-14 years), adolescent (15-19 years) and young
adult (20-39 years) leukaemia has improved substantially over the last five
decades, particularly for acute lymphoblastic leukaemia (ALL) and acute
promyelocytic leukaemia. This progress represents one of the most successful
achievements in the history of medicine and has been attributed to the
development of effective chemotherapy regimens, improvement in supportive care,
better risk stratification, use of targeted therapies, and advances in
haematopoietic stem cell transplantation. Recent studies have revealed
improvement in survival over time for all age groups and subtypes of leukaemia.
However, these outcomes varied widely by age and are associated with
sociodemographic and clinical factors. The present review concludes that survival
and early death after acute leukaemia has greatly improved among young patients.
However, inequalities in outcomes remain and are likely a result of multiple
factors.
PMID- 28693129
TI - Identification of anti-tumor components from toad venom.
AB - Secretion of granular glands from the skin of amphibians is a fascinating
resource of active substances, particularly for cancer therapy in clinical
practice of Traditional Chinese Medicine. A variety of anti-tumor peptides have
been isolated from different toads and frogs; however, no anti-tumor peptides are
reported in toad venom of Bufo gargarizans. Firstly, soluble fraction from fresh
toad venom (FTV) was compared with that from dried toad venom (DTV), using HPLC
analysis. It was revealed that FTV has a different HPLC chromatography compared
with DTV. Soluble fraction of FTV is more toxic to SH-SY5Y cells than that of
DTV, as evaluated by MTT assay. Secondly, it was identified that protein
components from soluble fractions of FTV and DTV possess different patterns by
SDS-PAGE analysis, and proteins from FTV are also more toxic than that from DTV.
Thirdly, an immobilized basic fibroblast growth factor (bFGF) affinity column was
used to isolate bFGF-binding components from soluble fraction of FTV, and it was
identified that bFGF-binding components prohibited bFGF-dependent neurite growth
of SH-SY5Y cells. Finally, it was identified that bFGF-binding components
activated apoptosis via upregulation of caspase-3 and caspase-8 expression in SH
SY5Y cells. These data suggest that FTV contains active components that interact
with bFGF and activate apoptosis in SH-SY5Y cells.
PMID- 28693130
TI - Novel association of MEN1 gene mutations with parathyroid carcinoma.
AB - Inactivating mutations of the multiple endocrine neoplasia 1 (MEN1) gene cause
MEN1 syndrome, characterized by primary hyperparathyroidism (pHPT), and
parathyroid and gastro-entero-pancreatic pituitary tumors. At present, only 14
cases of malignant parathyroid tumor have been associated with the syndrome, with
6 cases carrying an inactivating mutation of the MEN1 gene. The present study
presents the case of a 48-year-old female who presented with multigland pHPT and
multiple pancreatic lesions. The patient underwent surgery several times for the
excision of parathyroid hyperplasia, carcinoma and adenoma. The MEN1 gene was
screened, revealing three variants (in cis) at the intron/exon 3 boundary (IVS2
3G>C, c.497A>T and c.499G>T) detected on the DNA of the proband, not shared by
her relatives. RNA sequencing revealed that the IVS2-3C>G variant caused the
skipping of the exon 3. Therefore, the present study reports on a novel rare
association of MEN1 syndrome and parathyroid carcinoma. The reported splicing
mutation was previously identified in subjects who always developed malignant
lesions; thus, a possible genotype-phenotype association may be considered.
PMID- 28693131
TI - Metastases of transverse colon cancer to bilateral ovaries (Krukenberg tumor) and
the left breast: A case report.
AB - Breast cancer has the highest rate of incidence among all types of cancer in
women. Only ~0.43% of breast malignancies occur as a result of metastatic lesions
from extramammary tumors. The present study reports an extremely rare case of
transverse colon cancer metastasizing to the bilateral ovaries and the left
breast. The patient was a 47-year old female, who had a lump in the left breast
without axillary lymphadenopathy. Specimens obtained by core needle biopsy were
submitted for hematoxylin and eosin examination, and results revealed that the
lump was a poorly differentiated adenocarcinoma. Since the patient had elevated
levels of the carcinoembryonic antigen and a medical history of a Krukenberg
tumor metastasized from colon cancer, immunohistochemical examinations were
applied. Results identified that caudal-related homeobox protein 2 and
cytokeratin 20 were positively stained, whilst cytokeratin 7 was negatively
stained. Therefore, this patient was diagnosed as having colon cancer that had
metastasized to the bilateral ovaries and the left breast. As the life expectancy
of patients with cancer is increasing, types of metastases that used to be seen
as rare are increasingly becoming more common. For clinicians, diagnosis should
be cautious, and differential diagnosis should always be kept in mind.
PMID- 28693132
TI - Expression of 4-hydroxynonenal in esophageal squamous cell carcinoma.
AB - Esophageal squamous cell carcinoma (ESCC) is one of the most common types of
cancer in Asia, particular in China. However, the pathogenesis of ESCC has not
previously been well demonstrated. A major product of lipid peroxidation, 4
hydroxynonenal (4-HNE), is considered to be an oxidative stress inducer, as it is
involved in the pathogenesis of a number of degenerative diseases, including
Alzheimer's disease, atherosclerosis, cataracts and cancer. In order to
investigate the association between oxidative stress and the pathogenic process
of ESCC, the present study determined the expression levels of 4-HNE in 23 non
malignant esophageal epithelial tissues, 11 esophageal carcinoma in situ tissues
and 57 ESCC tissues from patients in the Chaoshan area, a high-risk region for
esophageal cancer in China. A significantly higher expression level of 4-HNE was
identified in ESCC tissues compared with that in non-malignant esophageal
epithelial tissues (P<0.05). Furthermore, immunohistochemical analysis
demonstrated that expression levels of 4-HNE were significantly associated with
the clinical stage. The patients with positive staining of 4-HNE revealed a
poorer clinical outcome compared with that of patients with negative staining. 4
HNE was significantly associated with the severity of inflammation and increased
with the progression of precancerous lesions (P<0.05). These results provide
pathological evidence that oxidative stress is a driving force of ESCC
carcinogenesis.
PMID- 28693133
TI - Overexpression of the X-linked ribosomal protein S4 predicts poor prognosis in
patients with intrahepatic cholangiocarcinoma.
AB - X-linked ribosomal protein S4 (RPS4X) has previously been reported to be
associated with cisplatin resistance and clinical outcome in bladder and ovarian
cancer. However, the value of RPS4X as a diagnostic and prognostic marker in
intrahepatic cholangiocarcinoma (ICC) has not yet been investigated. The present
study evaluated the expression pattern, and diagnostic and prognostic value of
RPS4X in patients with ICC. Retrospective analysis was performed for a total of
201 patients with intrahepatic cholangiocarcinoma, and 8 patients with
inflammation of the bile duct. Immunohistochemistry was performed using tissue
microarrays to characterize the expression profile of RPS4X. Receiver operating
characteristic (ROC) curves, the Kaplan-Meier estimator and Cox regression
analysis were applied to evaluate the potential diagnostic and prognostic value
of RPS4X in ICC. RPS4X was significantly upregulated in ICC tissues compared with
the inflamed bile duct tissues. When differentiating ICC from normal controls,
ROC analysis of RPS4X gave an area under the curve value of 0.9030 (sensitivity,
82.59%; specificity, 100%). RPS4X expression was significantly positively
correlated with serum alkaline phosphatase levels. Survival analysis demonstrated
that RPS4X expression levels were an independent prognostic factor for overall
survival. Therefore, RPS4X expression levels may serve as a novel diagnostic and
prognostic marker in ICC.
PMID- 28693134
TI - Prevalence and clinical significance of mediator complex subunit 12 mutations in
362 Han Chinese samples with uterine leiomyoma.
AB - Uterine leiomyomas (ULs) are the most common gynecological benign tumors
originating from the myometrium. Prevalent mutations in the mediator complex
subunit 12 (MED12) gene have been identified in ULs, and functional evidence has
revealed that these mutations may promote the development of ULs. However,
whether MED12 mutations are associated with certain clinical characteristics in
ULs remains largely unknown. In the present study, the potential mutations of
MED12 and its paralogous gene, mediator complex subunit 12-like (MED12L), were
screened in 362 UL tumors from Han Chinese patients. A total of 158 out of 362 UL
tumors (43.6%) were identified as harboring MED12 somatic mutations, and the
majority of these mutations were restricted to the 44th residue. MED12 mutations
were also observed in 2 out of 145 (1.4%) adjacent control myometrium.
Furthermore, the mutation spectrum of MED12 in the concurrent leiomyomas was
noticeably different. Correlation analysis of MED12 mutations with the available
clinical features indicated that patients with mutated MED12 tended to have
smaller cervical diameters. By contrast, no MED12L mutation was identified in the
present samples. In summary, the present study demonstrated the presence of
prevalent MED12 somatic mutations in UL samples, and the MED12 mutation was
associated with smaller cervical diameters. The low mutation frequency of MED12
in adjacent control myometrium indicated that MED12 mutation may be an early
event in the pathogenesis of ULs. Furthermore, MED12 mutation status in
concurrent tumors from multiple leiomyomas supported several prior observations
that the majority of these tumors arose independently.
PMID- 28693135
TI - C59T mutation in exon 2 of monocytic leukemia-associated antigen-34 gene
indicates a high risk of recurrence of acute myeloid leukemia.
AB - Monocytic leukemia-associated antigen-34 (MLAA-34) is a novel monocytic leukemia
associated antigen and a candidate oncogene. The aim of the present study was to
investigate the involvement of the MLAA-34 gene in acute myeloid leukemia (AML).
MLAA-34 expression level, chromosome location, gene copy number and single
nucleotide polymorphisms (SNPs) of 40 patients with AML and 5 healthy volunteers
were analyzed by reverse transcription-polymerase chain reaction, fluorescence in
situ hybridization and DNA sequencing. The effects of MLAA-34 mutation on overall
survival (OS) and progression-free survival (PFS) of patients with AML were also
analyzed. MLAA-34 was significantly upregulated in patients with AML when
compared with volunteer controls, and this upregulation was associated with a
C59T SNP site located in the second exon of MLAA-34. MLAA-34 was mapped to
13q14.2 and no translocation was observed in patients with AML. In addition, this
SNP site is affinitive to the well-known molecular markers of AML, including Fms
like tyrosine kinase 3 and DNA methyltransferase 3A, as well as extramedullary
lesions, periphery leukocyte numbers, remission and cytogenetic abnormalities of
patients with AML. Patients with AML with MLAA-34 C59T mutations had
significantly shorter OS and PFS times compared with that of patients without
C59T mutations. The present findings indicated that the MLAA-34 C59T mutation was
a high-risk factor for recurrence of AML, and may be a candidate target for AML
therapy.
PMID- 28693136
TI - Overexpression of sphingosine kinase 1 is predictive of poor prognosis in human
breast cancer.
AB - Sphingosine kinase 1 (SPHK1) is a bioactive lipid mediator that has been
identified as a biomarker in various cancers and is considered to play an
important role in tumor progression. In the present study, the expression level
of SPHK1 was examined in breast cancer clinical specimens, and its association
with patient survival was investigated to clarify the clinical significance of
SPHK1 in breast cancer. SPHK1 mRNA expression was increased in breast cancer
tissues compared with that in matched adjacent breast tissues in 19 of 32 paired
tissue specimens (59.4%). Immunohistochemical analysis of 122 breast cancer cases
revealed that the expression levels of SPHK1 were upregulated in 64 tumor tissues
(52.5%), and increased expression levels of the protein were significantly
associated with the presence of lymph node metastasis (P=0.0016), number of
positive lymph nodes (P=0.0268) and presence of distant metastasis (P=0.0097).
Increased SPHK1 protein expression was also associated with human epidermal
growth factor receptor 2 status (P=0.0100), initial symptoms (P=0.0025) and tumor
location (P=0.0457). Patients with increased SPHK1 protein expression had shorter
overall survival and disease-free survival times compared with patients with
lower SPHK1. Univariate and multivariate analyses indicated that high SPHK1
expression may be a poor prognostic factor. These results indicated that SPHK1
may perform an important role in breast cancer and may be a predictive factor in
patients with breast cancer.
PMID- 28693137
TI - Treatment outcome analysis of chemotherapy combined with modulated electro
hyperthermia compared with chemotherapy alone for recurrent cervical cancer,
following irradiation.
AB - The survival of patients with recurrent cervical cancer following irradiation
remains poor. Chemotherapy combined with hyperthermia has been demonstrated to
improve the response rate. The present study was performed to evaluate the effect
of modulated electro-hyperthermia combined with conventional chemotherapy
compared with chemotherapy alone on recurrent cervical cancer previously treated
with irradiation. A total of 20 patients were treated with chemotherapy alone,
and 18 were treated with chemotherapy combined with modulated electro
hyperthermia. A single patient was treated with chemo-radiotherapy as primary
treatment and then relapsed; the tumor was inoperable and radio-refractory upon
recurrence. Local metastases, including metastasis of the para-aortic lymph nodes
and adjacent pelvic lymph nodes were included, but distant metastases were
excluded. Modulated electro-hyperthermia was performed three times per week
beginning at chemotherapy initiation, and patients underwent a total of 36
sessions. The overall response (complete remission + partial remission + stable
disease/progressive disease) to treatment was significantly greater in the group
of patients who underwent chemotherapy combined with modulated electro
hyperthermia (P=0.0461), and at the evaluation conducted at the last follow-up
visit, the response rate was significantly higher (P=0.0218). Additionally,
severe complications were not reported. In the present study, of patients with
recurrent cervical cancer previously treated with irradiation, the overall
response rate for patients treated with chemotherapy combined with modulated
electro-hyperthermia was significantly greater than that for those treated with
chemotherapy alone.
PMID- 28693138
TI - Mammographic calcification can predict outcome in women with breast cancer
treated with breast-conserving surgery.
AB - The impact of calcification in patients with breast carcinoma treated with breast
conserving surgery (BCS) is unclear. The present study aimed to determine the
outcome of breast cancer patients with calcification treated with BCS. The
records of 409 patients with breast carcinoma treated with BCS from January 2005
to December 2008 were reviewed. Patients were categorized as those with
calcification (on mammography or ultrasonography), or those without calcification
(neither on mammography nor ultrasonography). The local relapse free survival
time (LRFS), disease free survival time (DFS) and overall survival time (OS) were
compared, and subgroup analysis was performed based on morphological types and
distribution patterns of mammographic calcification. Survival analysis
demonstrated that patients with calcification had a significantly increased risk
of local recurrence, distant metastasis and mortality compared with those without
calcification [relative risk (RR) and 95% confidence interval (CI): local
recurrence, 2.46 and 1.11-5.44; distant metastasis, 2.24 and 1.19-4.24;
mortality, 2.50 and 1.06-5.86]. Subgroup analysis revealed that the distribution
patterns (rather than morphological types of calcification) accounted for the
increased risk of recurrence following BCS. Patients with mammographic
calcification of liner/segmental distribution had significantly decreased LRFS
(RR=6.20; 95% CI, 2.26-16.98), DFS (RR=6.81; 95% CI, 2.86-16.20) and OS (RR=9.14;
95% CI, 2.53-33.00), while patients with mammographic calcification of clustered
distribution did not have significantly decreased LRFS, DFS and OS (P>0.05),
compared with those without calcification. In addition, the mammographic
calcification spreading along the ducts was more likely to be accompanied by an
extensive intraductal component (P<0.001). Finally, the outcome of patients with
calcification on breast ultrasound was as good as those without calcification.
Patients with mammographic calcification, particularly those with calcification
spreading along the ducts, have a higher risk of recurrence following BCS, which
has a negative impact on long-term survival. Calcification identified on breast
ultrasonography does not affect the survival of patients treated with BCS.
PMID- 28693139
TI - Azithromycin effectively inhibits tumor angiogenesis by suppressing vascular
endothelial growth factor receptor 2-mediated signaling pathways in lung cancer.
AB - Tumor angiogenesis is essential during lung cancer development and targeting
angiogenesis may possess a potential therapeutic value. The present study
demonstrates that azithromycin, a Food and Drug Administration-approved
antibiotic drug, is a novel tumor angiogenesis inhibitor. Azithromycin inhibits
capillary network formation of human lung tumor associated-endothelial cells (HLT
ECs) in vitro and in vivo. It significantly inhibits HLT-EC adhesion and vascular
endothelial growth factor (VEGF)-induced proliferation of HLT-ECs in a dose
dependent manner without affecting migration. In addition, azithromycin induces
apoptosis of HLT-ECs even in the presence of VEGF. Notably, azithromycin inhibits
proliferation and induces apoptosis in multiple lung cancer cell lines to a
significantly reduced extent compared with in HLT-ECs, suggesting that HLT-ECs
are more susceptible to azithromycin treatment. In a lung tumor xenograft model,
azithromycin significantly inhibits tumor growth and its anti-tumor activities
are achieved by suppressing angiogenesis. Notably, the inhibitory effects of
azithromycin on angiogenesis are associated with its ability to suppress VEGF
induced activation of VEGF receptor 2 (VEGFR2), phosphoinositide 3-kinase
(PI3K)/protein kinase B (Akt), focal adhesion kinase, and disruption of focal
adhesion assembly and actin stress fiber formation in HLT-ECs. The present study
identifies that azithromycin targets VEGFR2-mediated focal adhesion and PI3K/Akt
signaling pathways in HLT-ECs, leading to the suppression of angiogenesis and
lung tumor growth.
PMID- 28693140
TI - Acute myeloid leukemia with t(3;21)(q26.2;q22) developing following low-dose
methotrexate therapy for rheumatoid arthritis and expressing two AML1/MDS1/EVI1
fusion proteins: A case report.
AB - The t(3;21)(q26.2;q22) translocation is a rare chromosomal abnormality exhibited
almost exclusively in therapy-related myelodysplastic syndrome/acute myeloid
leukemia (t-MDS/AML) or in the blastic crisis phase of chronic myelogenous
leukemia, which results in the fusion of the runt related transcription factor 1
(RUNX1, also called AML1) gene at 21q22 to the myelodysplasia syndrome 1 (MDS1)
ecotropic virus integration site 1 (EVI1) complex locus (MECOM) at 3q26.2,
generating various fusion transcripts, including AML1/MDS1/EVI1 (AME). The
present study examined the case of an 84-year-old Japanese woman who developed t
MDS/AML with t(3;21)(q26.2;q22) subsequent to receiving low-dose methotrexate
(MTX) treatment for rheumatoid arthritis. Following treatment with MTX for 6
years, the patient developed anemia and neutropenia, and MTX was discontinued. A
total of 3 years later, the patient was diagnosed with MDS with
t(3;21)(q26.2;q22) and del (5q), which progressed rapidly to AML within 3 months.
The patients was subsequently treated with azacitidine and cytarabine
chemotherapy, but succumbed to the disease 6 months after diagnosis. Sequencing
analysis of the nested reverse transcription-PCR products from the leukemic cells
revealed the expression of two types of alternatively-spliced AME transcripts
with or without RUNX1 exon 6 sequences. Western blot analysis of the leukemic
cells of the patient additionally revealed that the corresponding AME fusion
protein products were expressed at high levels, and that these cells also
prominently expressed CCAAT/enhancer-binding protein alpha, the repression of
which has been reported to be involved in leukemogenesis mediated by AME. To the
best of our knowledge, the case discussed in the present study represents the
first report of MDS/AML with t(3;21)(q26.2;q22) developing following low-dose MTX
therapy for rheumatoid arthritis. Nonetheless, the clinical and molecular
features of the patient in the present study were representative of those
patients who typically develop this disease following exposure to chemotherapy or
radiotherapy for primary malignancy, which implicates MTX in the pathogenesis of
t-MDS/AML. Moreover, we confirmed the expression of two AME fusion proteins for
the first time in primary leukemic cells and analyzed several cellular factors
implicated in AME-mediated leukemogenesis to gain some insight into its molecular
mechanisms.
PMID- 28693141
TI - Effect of 2-methoxyestradiol on SK-LMS-1 uterine leiomyosarcoma cells.
AB - An endogenous metabolite of 17beta-estradiol, 2-methoxyestradiol (2-ME), has
affinity for estrogen receptors. This compound was reported to be a promising
antitumor drug due to its anti-proliferative effects on a wide range of tumor
cell types. Numerous previous studies have been performed to evaluate the
cytotoxic effects of 2-ME on tumor cell lines in following the induction of G2/M
cell cycle arrest and subsequent apoptosis. Uterine leiomyosarcoma (ULMS) is a
relatively rare malignant smooth muscle cell tumor that develops in the uterus
muscle layer. The aim of the present study was to examine the in vitro anti
proliferative effects of 2-ME on SK-LMS-1 human leiomyosarcoma cells. An MTT
assay, terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling
assay, immunocytochemistry and western blotting were performed. A high
concentration (10-5 M) of 2-ME was identified to have an anti-proliferative
effect on SK-LMS-1 cells. Additionally, expression of the apoptosis markers was
upregulated in the presence of 10-5 M 2-ME, according to western blot analysis.
Furthermore, the expression level of an autophagic marker, light chain 3, was
increased by 2-ME treatment in a dose-dependent manner. This was associated with
cell death induced by the upregulation of phosphorylated extracellular-signal
regulated kinase 1/2 signaling pathway. The results of the present study
demonstrated that 2-ME, which is used as a therapeutic agent for treating solid
tumors, exhibits apoptotic and anti-proliferative effects depending on the dose.
Therefore, 2-ME may be a potential therapeutic reagent for human ULMS, but the
appropriate dose of this compound should be carefully selected.
PMID- 28693142
TI - MicroRNA-4530 promotes angiogenesis by targeting VASH1 in breast carcinoma cells.
AB - The results of our previous study revealed that microRNA (miRNA/miR)-4530 was
upregulated in the serum of patients with diabetic retinopathy. The TargetScan
miRNA database was used to identify potential targets of miR-4530 and vasohibin-1
(VASH1) was predicted as one of the targets. The results of our previous study
demonstrated that miR-4530 was able to promote angiogenesis in human umbilical
vein endothelial cells. Therefore, suppressing miR-4530 may be a potentially
novel approach towards inhibiting tumor angiogenesis. The present study aimed to
investigate the function of miR-4530 and determine whether miR-4530 was able to
regulate angiogenesis in breast carcinoma cells by targeting VASH1. MDA-MB-231
and MCF-7 cells were transfected with miR-4530 precursor, anti-miR-4530 and empty
vector plasmids. The expression levels of miRNA and mRNA were detected using the
reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The
expression levels of protein were detected using western blotting. Dual
luciferase reporter assays were used to identify the target of miR-4530.
Furthermore, cell proliferation, cell cycle, apoptosis and tube formation assays
were used to investigate the function of miR-4530 in vitro. Nude mice were used
in a subcutaneous tumor model in vivo study. The results of the present study
demonstrated that miR-4530 significantly suppressed proliferation and promoted
apoptosis of breast carcinoma cells. In addition, miR-4530 expression promoted
angiogenesis in vitro. Results from the western blotting and RT-qPCR revealed
that VASH1 was significantly downregulated by miR-4530 in breast carcinoma cells.
The results of the present study suggest that miR-4530 promotes angiogenesis,
inhibits proliferation and induces apoptosis in breast carcinoma cells by
suppressing the expression of VASH1.
PMID- 28693143
TI - Altered expression of cytokeratin 7 and CD117 in transitional mucosa adjacent to
human colorectal cancer.
AB - The multi-step progression of colorectal cancer through precancerous lesions
(adenoma and dysplasia) is associated with cumulative molecular alterations, a
number of which have also been demonstrated to be present in morphologically
normal transitional mucosa adjacent to colorectal cancer. The cytoskeletal
protein cytokeratin 7 (CK7) and the receptor tyrosine kinase, KIT proto-oncogene
receptor tyrosine kinase (CD117), encoded by the proto-oncogene c-Kit, are
lacking in normal colorectal crypt epithelium and are aberrantly expressed in a
subset of colorectal cancer. The aim of the present study was to evaluate the
expression of CK7 and CD117 in morphologically normal transitional mucosa
adjacent to colorectal cancer. Immunohistochemical staining for CK7 and CD117 was
performed in the mucosa adjacent to five groups of surgically resected colorectal
tumors [low-grade adenoma, high-grade adenoma, mucosal adenocarcinoma, small
sized invasive adenocarcinoma (<=2 cm) and large-sized invasive adenocarcinoma
(>2 cm)]. CK7 was expressed in the mucosa adjacent to a subset of colorectal
tumors, and the positivity ratio increased according to tumor grade from low
grade adenoma up to small-sized invasive adenocarcinoma (61.2%). However, the
positivity ratio of CK7 in the mucosa adjacent to the large-sized invasive
adenocarcinoma (25.0%) was significantly lower compared with that of the next
lower grade. CD117 was also expressed in the mucosa adjacent to a subset of
colorectal tumors. In contrast to CK7, the positivity ratio of CD117 increased
according to tumor grade from low-grade adenoma all the way through to the large
sized invasive adenocarcinoma (45.0%). Based on these results, the mechanism of
CK7 and CD117 expression in the transitional mucosa adjacent to colorectal cancer
may be different, and analysis of their individual expression may provide novel
insights into the development and progression of colorectal cancer.
PMID- 28693144
TI - Denosumab-related osteonecrosis of the jaw in a patient with bone metastases of
prostate cancer: A case report and literature review.
AB - Denosumab, a human monoclonal antibody directed against the receptor activator of
nuclear factor-kappabeta ligand (RANKL), is used for the treatment of patients
with metastatic cancer of the bone or osteoporosis. Recent reports have
demonstrated that denosumab can induce osteonecrosis of the jaw (ONJ), but
reported cases of this are uncommon. The present study reports the case of an 86
year-old male with prostate cancer patient exhibiting bone metastases who
developed ONJ whilst receiving denosumab. To elucidate the influence of denosumab
on the development of ONJ, the present study also reviewed the literature,
including clinical trials and case reports. In the clinical trials, the
prevalence of denosumab-related ONJ was higher in patients with cancer compared
with those with osteoporosis. The high risk of ONJ in patients with cancer was
thought to be associated with the differing dose and frequency of denosumab
administration. The prevalence of ONJ was not significantly different between
patients receiving denosumab and bisphoshonate (BP). In the reported cases,
denosumab-related ONJ had a similar clinical presentation to BP-related ONJ.
There was also a tendency for denosumab-related ONJ to develop in the mandible of
elderly patients. Previous invasive dental treatment was a commonly shared
characteristic of patients with denosumab-related ONJ. A complex medical history
was also suspected to affect the prevalence. No clear association between the
dose or duration of denosumab treatment and the development of ONJ was observed.
Although conservative treatments are given for denosumab-related ONJ, non
improving cases were managed surgically with primarily positive results. Because
denosumab may offer superior results compared with BP for the treatment of
metastatic cancer of the bone or osteoporosis, the use of denosumab is expected
to increase in the near future. Clinicians should also be aware of the risk
factors for denosumab-related ONJ, in order to aid in its diagnosis. In addition,
patients treated with denosumab should receive prophylactic treatment to maintain
their oral health prior to, during and after denosumab treatment.
PMID- 28693145
TI - Association between chromosomal aberration of exfoliated bladder cells in the
urine and oxidative stress in patients with bladder transitional cell carcinoma.
AB - The aim of the current study was to investigate the chromosomal aberrations of
exfoliated bladder cells in the urine and blood oxidative stress in patients with
bladder transitional cell carcinoma (BTCC). A total of 40 healthy controls and
246 patients with BTCC were recruited. Abnormal levels of CSP3, CSP7, CSP17 and
GLPp16 were detected by fluorescence in situ hybridization (FISH) in exfoliated
bladder cells in the urine of patients with BTCC. Serum total oxidant status
(TOS), total antioxidant status (TAS) and oxidative stress index (OSI) were
measured. Significant differences were observed in the abnormal CSP3, CSP7,
CSP17, GLPp16 signals and FISH positive rate between patients with BTCC and
healthy controls (P<0.001). Serum TOS, TAS and OSI were also significantly
different between the two groups (P<0.001). The clinical stage of BTCC was not
associated with abnormal CSP3, CSP7, CSP17, GLPp16 or FISH positive rate and
oxidative stress (P>0.05). A Gamma rank correlation analysis revealed an
association between the pathological grade of BTCC with abnormal CSP3, CSP7 and
CSP17 as well as FISH positive rate (P<0.001). In addition, the clinical stage of
BTCC was associated with serum TOS, TAS and OSI (P<0.001). Evaluation of the
association between chromosomal aberrations and oxidative stress revealed that
abnormal CSP3, CSP7 and CSP17 were positively associated with serum TOS and OSI
(P<0.001), abnormal CSP7 and CSP17 were negatively associated with serum TAS
(P<0.001), but abnormal GLPp16 was not associated with serum TOS, TAS or OSI
(P>0.05). Therefore, the chromosomal aberrations of exfoliated bladder cells in
the urine are associated with blood oxidative stress in patients with BTCC, and
these factors may contribute to the occurrence and development of BTCC.
PMID- 28693146
TI - Inhibition of paclitaxel resistance and apoptosis induction by cucurbitacin B in
ovarian carcinoma cells.
AB - Ovarian cancer is the leading cause of mortality among all gynecological
malignancies. Drug resistance is a cause of ovarian cancer recurrence and low
rate of overall survival. There is a requirement for more effective treatment
approaches. Cucurbitacin B (CuB) is an antineoplastic agent derived from
traditional Chinese medicinal herbs. Its activity against paclitaxel-resistant
human ovarian cancer cells has, however, not yet been established. The purpose of
the present study was to investigate the effect and mechanism of CuB on human
paclitaxel-resistant ovarian cancer A2780/Taxol cells. Cell viability was
evaluated by a cell counting assay, while cell cycle arrest and apoptosis were
assessed by microscopy and flow cytometry, and proteins associated with apoptotic
pathways and drug resistance were evaluated by western blotting. The present
results demonstrated that CuB exerts dose- and time-dependent cytotoxicity
against the ovarian cancer A2780 cell line, with half-maximal inhibitory
concentration (IC50) values 0.48, 0.25 and 0.21 uM following 24, 48 and 72 h of
incubation, respectively. Compared with its sensitive counterpart, A2780,
paclitaxel-resistant A2780/Taxol cells had almost identical IC50 values. Cell
cycle analysis demonstrated that treatment with CuB may induce cell cycle arrest
at the G2/M phase of the cell cycle in the two cell lines. As revealed by Annexin
V/propidium iodide-labeled flow cytometry and Hoechst 33258 staining, CuB-induced
apoptosis was accompanied by activation of caspase-3 and downregulation of B-cell
lymphoma-2. Western blotting demonstrated that CuB may enhance the expression of
p53 and p21 in the two cell lines. CuB may also downregulate the expression of P
glycoprotein. These results indicate that CuB may exert a therapeutic effect on
paclitaxel-resistant human ovarian cancer.
PMID- 28693147
TI - Pancreatic intraductal tubulopapillary neoplasm with associated invasive cancer
successfully treated by total pancreatectomy: A case report.
AB - A 74-year-old male was admitted to Departments of Surgery, Toyonaka Municipal
Hospital (Osaka, Japan) for treatment of a pancreatic tumor. Contrast enhanced
computed tomography (CT) revealed a mass with small cystic lesions in the
pancreatic head and body. Fluorodeoxyglucose-positron emission tomography/CT
revealed an abnormal uptake of fluorodeoxyglucose, corresponding to the mass
lesions. Upper gastrointestinal endoscopy revealed rough mucosa near the opening
of the accessory pancreatic duct, and the mucosa biopsy exhibited adenocarcinoma
with no mucin observed. The preoperative diagnosis was pancreatic intraductal
tubulopapillary neoplasm (ITPN) with cancerous lesions, and a total
pancreatectomy with splenectomy was performed. The resected tissue specimen
revealed a solid tumor occupying the entire pancreas with intraductal growth into
the main pancreatic duct. Histological examination revealed high-grade dysplastic
cells in a tubulopapillary growth pattern without overt mucin production beyond
the pancreatic duct. Immunohistochemical staining analysis of the tumor was
positive for cytokeratin (CK)7, CK19 and mucin (MUC)1, and negative for MUC2,
MUC5AC, MUC6 and caudal type homeobox 2. The tumor was finally diagnosed as
pancreatic ITPN with associated invasive cancer. The patient remains well without
evident recurrence nine months post-surgery. ITPN is a rare type of epithelial
neoplasm of the pancreas, and is characterized by intraductal tubulo-papillary
growth, ductal differentiation, limited intracellular mucin production, and
cellular dysplasia. The present case report may contribute to improved
understanding of how to effectively treat patients with ITPN.
PMID- 28693148
TI - Expression levels and clinical significance of hepsin and HMGB1 proteins in
cervical carcinoma.
AB - This study assessed the hypothesis that the protein levels of high mobility group
box 1 (HMGB1) and hepsin can be used as markers for diagnosis and prognosis in
cervical carcinoma. Seventy patients with cervical cancer who were hospitalized
in Xuzhou Central Hospital from May 2008 to June 2010 and underwent surgical
treatment were selected for the observation group. At the same time, 20 patients
with cervical benign lesions who underwent tumor stripping or accessory resection
were selected for the control group. Immunohistochemical (SP) detection methods
were used to detect hepsin and HMGB1 protein levels in tissues. The positive
rates of HMGB1 cells in normal, paracancerous and cancerous cervical tissues were
5.0% (1/20), 22.9% (16/70) and 95.7% (67/70) (F=24.581, P=0.001) respectively.
The positive rates of hepsin in normal, paracancerous and cancerous cervical
tissues were respectively 10% (2/20), 61% (43/70) and 90% (63/70) (F=11.538,
P=0.001). The HMGB1 expression level was related to the degree of tumor
differentiation, lymph node metastasis and TNM stage (P<0.05). While the level of
hepsin expression was related to the degree of tumor differentiation, invasion
depth, lymph node metastasis and TNM stage (P<0.05). Furthermore, a positive
correlation between the levels of hepsin and HMGB1 was found (r=15.27, P<0.05).
The overall 5-year survival rates of patients with high expression of HMGB1 (+++)
and low expression of HMGB1 (+ to ++) were respectively 51.2 and 29.2%
(HR=11.637, 95% CI=4.351-38.213; P=0.002). The overall 5-year survival rates of
patients with high hepsin expression (+++) and low hepsin expression (+ to ++)
were respectively 41.3 and 35.3% (HR=10.143, 95% CI=4.285-33.275; P=0.006). Based
on our results, the higher the levels of expression of hepsin and HMGB1 in
tissues the higher the degree of invasiveness of the cervical cancers, and the
worse the prognoses for the patient.
PMID- 28693149
TI - Comparison of different methods for nutrition assessment in patients with tumors.
AB - Nutrition screening to identify patients at risk of malnutrition is vital for
cancer patients because of the high prevalence of malnutrition in this
population. The aim of the present study was to compare different methods of
nutrition assessment in patients with tumors. From June 2013 to June 2014, we
conducted an observational multicenter study to compare the assessment of
nutritional status in patients with tumors by anthropometry, biochemical
indicators, nutritional risk screening (NRS-2002) and patient-generated
subjective global assessment (PG-SGA). Mann-Whitney test and Kruskal-Wallis H non
parametric test were used for intergroup comparisons. Spearmans rank correlation
coefficients were calculated to evaluate the association between different
methods of nutritional assessment. The kappa statistic was used to evaluate the
agreement between two assessment methods. A total of 927 oncology inpatients
underwent full nutritional assessment and nutrition screening. The PG-SGA tool
determined that 13.7% of patients were well-nourished (PG-SGA from 0-1) and the
rest (86.3%) were malnourished. Among the malnourished patients, 57.8% were
moderately malnourished (PG-SGA from 2-8) and 28.5% were severely malnourished
(PG-SGA >=9). According to NRS-2002, 30.7% of patients were at nutritional risk
(NRS-2002 >=3). There was a significant positive correlation between PG-SGA
scores and NRS-2002 scores in both men and women. Compared to albumin, the PG-SGA
had a sensitivity of 93.78% and specificity of 21.80%. In comparison, NRS-2002
had a low sensitivity of 43.13% and relatively higher specificity of 82.16%. In
conclusion, the relationship between PG-SGA, NRS-2002 and nutritional status is
statistically significant. Compared with NRS-2002, PG-SGA is a suitable screening
tool for detecting the risk of malnutrition in patients with cancer.
PMID- 28693150
TI - DHFR and MDR1 upregulation is associated with chemoresistance in osteosarcoma
stem-like cells.
AB - Tumor-initiating cells (TICs) are defined as a specialized subset of cells with
tumor-initiating capacity that can initiate tumor growth, tumor relapse and
metastasis. In the present study, osteosarcoma TICs (OS-TICs) were isolated and
enriched from the osteosarcoma U2OS and MG-63 cell lines using sphere formation
assays and serum-depleted media. These enriched OS-TICs showed the expression of
several typical cancer stemness markers, including octamer-binding transcription
factor 4, Nanog homeobox, cluster of differentiation (CD)117, Nestin and CD133,
and the expression of ATP binding cassette subfamily G member 2, multidrug
resistance protein 1 (MDR1) and dihydrofolate reductase (DHFR). Notably, in vitro
and in vivo tumorigenic properties were enhanced in these OS-TICs. Additionally,
methotrexate and doxorubicin are the most widely used anticancer agents against
osteosarcoma, and the observed enhanced chemoresistance of OS-TICs to these two
agents could be associated with the upregulation of DHFR and MDR1. These findings
suggest that the upregulation of DHFR and MDR1 is associated with the development
of chemoresistance of OS-TICs.
PMID- 28693151
TI - Application of small intestine decompression combined with oral feeding in middle
and late period of malignant small bowel obstruction.
AB - The application value of small intestine decompression combined with oral feeding
in the middle and late period of malignant small bowel obstruction was examined.
A total of 22 patients with advanced malignant small bowel obstruction were
included in the present study. An ileus tube was inserted via the nose under
fluoroscopy into the obstructed small intestine of each patient. At the same
time, the insertion depth the of the catheter was adjusted. When the catheter was
blocked, small bowel selective angiography was performed to determine the
location and cause of the obstruction and the extent of the obstruction, and to
determine the length of the small intestine in the site of obstruction, and to
select the variety and tolerance of enteral nutrition. We observed the
decompression tube flow and ease of intestinal obstruction. In total, 20 patients
were treated with oral enteral nutrition after abdominal distension, and 22 cases
were treated by the nose to observe the drainage and the relief of intestinal
obstruction. The distal end of the catheter was placed in a predetermined
position. The symptoms of intestinal obstruction were relieved 1-4 days after
decompression. The 22 patients with selective angiography of the small intestine
showed positive X-ray signs: 18 patients with oral enteral nutrition therapy had
improved the nutritional situation 2 weeks later. In 12 cases, where there was
anal defecation exhaust, 2 had transient removal of intestinal obstruction
catheter. In conclusion, this comprehensive treatment based on small intestine
decompression combined with enteral nutrition is expected to become a new
therapeutic approach and method for the treatment of patients with advanced tumor
small bowel obstruction.
PMID- 28693152
TI - Multicenter research into the quality of life of patients with advanced
oropharyngeal carcinoma with long-term survival associated with human papilloma
virus.
AB - The treatment of advanced-stage oropharyngeal squamous cell carcinoma may utilize
various modes, including combining surgery with chemoradiotherapy (CTRT), or
primary CTRT followed by rescue surgery. In previous literature it has been
revealed how patients treated with combined modes report a low quality of life
(QoL) and severe consequences following surgery, radiotherapy and chemotherapy,
in the short and in the long-term. The decrease in the QoL of patients treated
with high-intensity multi-modal strategies highlights the necessity of modifying
treatments, particularly for young HPV-positive patients, where an increased
survival rate has already been reported. The modified treatment for HPV-positive
tumors in the tonsils and at the base of the tongue is based on the
deintensification of therapies aiming to reduce toxicity and thereby improve QoL
in the long term, whilst still maintaining therapeutic effectiveness. The aim of
the present study was to evaluate the QoL in patients with a long-term survival,
who were treated with combined therapy for squamous cell tumors in the tonsils
and at the base of the tongue, and to compare the results observed in HPV
positive and HPV-negative patients. According to statistical analysis,
differences in the general QoL and in the single scales of the European
Organization for the Research and Treatment of Cancer questionnaires were not
correlated with the type of therapy selected for the particular patient. QoL
considered the presence of HPV, the type of treatment, the subregion of the
tonsils vs. the base of the tongue and the disease stage at the time of
diagnosis, and was determined to be non-influential with regard to these specific
variables.
PMID- 28693153
TI - Clinical outcome of brain metastases differs significantly among breast cancer
subtypes.
AB - Brain metastases in patients with breast cancer are associated with a poor
survival rate. A small number of studies have challenged this premise, suggesting
that survival times following brain metastasis differ significantly between
breast cancer subtypes. In the current study, overall survival (OS), brain
metastases-free survival (BMFS) and survival following brain metastases (SFBM)
were found to be associated with the intrinsic breast cancer subtype. A total of
1,147 patients with invasive breast cancer who were treated at the Hannover
Medical School between January 2004 and December 2010 were included, from which
54 patients with brain metastases were identified. The Kaplan-Meier method or Cox
regression analyses were performed for analysis of survival. OS was found to
differ significantly between breast cancer subtypes: OS was significantly shorter
in patients with triple-negative (TN) cancer compared with patients with human
epidermal growth factor receptor (HER2)-enriched tumors (P<0.001). In addition,
median BMFS times differed significantly between luminal (1,003 days), HER2
enriched (514 days) and TN breast cancer patients (460 days) (P=0.045). The
median durations of SFBM were 386 days in luminal, 310 days in HER2-enriched and
147 days in TN breast cancer patients (P=0.029). The results suggested that
patients with luminal breast cancer have a lower risk of brain metastases and the
most favorable outcome with regard to BMFS, whereas patients with HER2-positive
or TN breast cancer have a significantly higher risk of developing brain
metastases. Compared with TN breast cancer, the duration of SFBM was doubled in
HER2-enriched cancers. These findings may have important implications for
treatment and follow-up strategies in patients with breast cancer.
PMID- 28693154
TI - Association between the expression of microRNAs and the response of patients with
locally advanced rectal cancer to preoperative chemoradiotherapy.
AB - Preoperative chemoradiotherapy (CRT) followed by mesorectal excision is the
standard treatment for patients with locally advanced rectal cancer (LARC). The
balance between treatment efficacy and toxicity is a major issue in the clinical
management of these patients. There is a requirement for the identification of
predictive molecular biomarkers for the response of patients to CRT. The present
study aimed to analyze the association between microRNA (miRNA/miR) expression
and treatment efficacy in patients with LARC who were treated with preoperative
CRT. From previous clinical trials, 55 patients for the test cohort and 130
patients for the validation cohort met the criteria for the present
investigation. Through reverse transcription-quantitative polymerase chain
reaction analysis, the expression of miR-21, -31, -125b, -145 and -630 in the
diagnostic biopsies was analyzed. The primary endpoint of tumor regression was
evaluated according to Mandard's Tumor Regression Grade (TRG) system. In the test
cohort, a significant association was identified between low miRNA-145 expression
and TRG1+2 (P=0.0003). Similarly, this association was identified in the
validation cohort, although it did not reach statistical significance.
Furthermore, a significant association between high miRNA-21 expression and
TRG1+2 (P=0.035) was observed in the validation cohort. The remaining miRNAs
analyzed were not associated with TRG. The results of the present study highlight
the clinical importance of miRNAs in LARC and underline the necessity for
validation studies in this setting.
PMID- 28693155
TI - Transrectal real-time tissue elastography targeted biopsy coupled with peak
strain index improves the detection of clinically important prostate cancer.
AB - The focus of the present study was to evaluate transrectal real-time tissue
elastography (RTE)-targeted two-core biopsy coupled with peak strain index for
the detection of prostate cancer (PCa) and to compare this method with 10-core
systematic biopsy. A total of 141 patients were enrolled for evaluation. The
diagnostic value of peak strain index was assessed using a receiver operating
characteristic curve. The cancer detection rates of the two approaches and
corresponding positive cores and Gleason score were compared. The cancer
detection rate per core in the RTE-targeted biopsy (44%) was higher compared with
that in systematic biopsy (30%). The peak strain index value of PCa was higher
compared with that of the benign lesion. PCa was detected with the highest
sensitivity (87.5%) and specificity (85.5%) using the threshold value of a peak
strain index of >=5.97 with an area under the curve value of 0.95. When the
Gleason score was >=7, RTE-targeted biopsy coupled with peak strain index
detected 95.6% of PCa cases, but 84.4% were detected using systematic biopsy.
Peak strain index as a quantitative parameter may improve the differentiation of
PCa from benign lesions in the prostate peripheral zone. Transrectal RTE-targeted
biopsy coupled with peak strain index may enhance the detection of clinically
significant PCa, particularly when combined with systematic biopsy.
PMID- 28693156
TI - Detection of OPCML methylation, a possible epigenetic marker, from free serum
circulating DNA to improve the diagnosis of early-stage ovarian epithelial
cancer.
AB - The aim of the present study was to identify the appropriate DNA sequence and
design high-quality primers for methylation-specific polymerase chain reaction
(MSP). These primers may be used to examine and identify patients with early
stage epithelial ovarian carcinoma (EOC). Opioid binding protein/cell adhesion
molecule like (OPCML), Runt-related transcription factor 3 and tissue factor
pathway inhibitor 2 were selected as possible molecular markers. MSP primer sets
were designed to monitor the methylation of the three markers. Free circulating
DNA (fcDNA) from 194 patients with epithelial ovarian carcinoma and healthy
donors were templates in the nested MSP. OPCML MSP was effective with respect to
screening methylated fcDNA. One-way ANOVA P-values indicated that the difference
in cancer antigen 125 (CA125), a biomarker for EOC diagnosis, level between early
EOC and healthy donors was not significant. The methylation of OPCML was
significantly altered in early-stage EOC compared with healthy donors (P<0.0001),
and this supported the hypothesis that specific fcDNA methylation was able to
distinguish patients with early-stage EOC from healthy donors. With respect to
detecting early EOC, compared with the results of the CA125 test, MSP increased
the kappa coefficient from 0.140 to 0.757. Therefore, OPCML combined with fcDNA
may be used to establish an improved clinical assay compared with the current
CA125 test.
PMID- 28693157
TI - Study on the association of the polymorphism of HLA-II gene with leukemia.
AB - We explored the association between the HLA-II gene polymorphisms and the
occurrence of leukemia. For this study, we selected 53 patients with leukemia
treated at Zhongnan Hospital of Wuhan University from February 2014 to September
2015 and 46 healthy patients as the control group. We used polymerase chain
reaction with sequence specific primers for DNA typing which was carried out to
analyze the patients HLA-A/B gene polymorphism. We also used enzyme-linked
immunosorbent assay and western blotting method to measure the protein expression
of different genotypes and activity. Compared to the control group, HLA-A04, B08
gene frequencies were significantly lower than those of HLA-A04, B08 gene
frequencies of the observation group; results were statistically significant
(chi2=16.28, P<0.05; chi2=16.47, P<0.05). However, in the control group, the
frequency of HLA-A09 gene was significantly higher than that of the observation
group; there was a significant difference between the two groups (chi2=15.28,
P<0.05). Through the measurement of the protein expression levels of the
different genotypes in the control group and the observation group, it was found
that in the observation group, HLA-A04, B08 protein contents (4.6 and 3.2 ug/l)
were significantly higher than those of the control group (0.13 and 0.1 ug/l).
While the control group HLA-A09 genotype protein content (3.7 ug/l) was
significantly higher than that of the observation group (0.2 ug/l); there were
significant differences between both (P<0.05). Therefore, there is a significant
correlation between HLA-II gene polymorphism and leukemia that is higher than HLA
A04 and B08 gene frequency and can help promote the occurrence of leukemia. The
higher frequency of HLA-A09 gene can help to suppress the occurrence of leukemia.
PMID- 28693158
TI - Relationship between MGMT gene expression and treatment effectiveness and
prognosis in glioma.
AB - The expression of O6-methylguanine DNA methyltransferase (MGMT) in different
grade gliomas were analyzed in relation to its therapeutic effect and impact on
disease prognosis. In total, 62 patients with glioma, who were admitted by
neurosurgery and received surgical treatment and postoperative conventional
chemoradiation, were selected for this study. Expression of MGMT was greater with
an increase in brain glioma grade. Gender, age, tumor size and Karnofsky
performance status (KPS) score did not differ with MGMT expression (P>0.05).
Expression of MGMT in normal brain tissue was slightly significantly different
than expression of MGMT in glioma tissue (P<0.05). The short-term efficacy and
survival time of the MGMT-negative expression group were better than those of
MGMT-positive expression. MGMT was only treated as an index to monitor tumor
recurrence or metastasis and a reference to judge the prognosis of patients. The
expression level of MGMT in glioma had no relation with age, gender, tumor size,
surgical approach and KPS score. For glioma patients with positive expression of
MGMT, antineoplastic drugs of alkylating agent class should be avoided.
PMID- 28693159
TI - Cantharidin alters the expression of genes associated with the NKG2D-associated
immune response in TSGH-8301 human bladder carcinoma cells.
AB - Cantharidin (CTD) is a natural toxin in beetles of the Mylabris genus (blister
beetle), which has been revealed to induce cell death in various types of human
cancer cells. However, to the best of our knowledge, no previous studies have
investigated the effect of CTD on the expression of genes and their associated
signaling pathways in human bladder carcinoma cells. In the present study, CTD
induced cell morphological changes and apoptosis were observed using phase
contrast microscopy and the terminal deoxynucleotidyl transferase dUTP nick end
labeling assay, respectively, in TSGH-8301 human bladder carcinoma cells. In
addition, a complementary DNA microarray analysis demonstrated that CTD treatment
led to a >2-fold upregulation of 269 genes. For example, the DNA damage
associated gene DNA-damage-inducible transcript 3 had a 4.75-fold upregulation.
Furthermore, another 286 genes were >2-fold downregulated in response to CTD
treatment. Matrix-remodeling associated 5, which is associated with cell
migration and invasion, was downregulated 7.98-fold.
PMID- 28693160
TI - Isoliquiritigenin induces apoptosis of human bladder cancer T24 cells via a
cyclin-dependent kinase-independent mechanism.
AB - The aim of the present study was to investigate whether an increase in cyclin
dependent kinase 2 (CDK2) activity is involved in apoptosis of human bladder
cancer T24 cells induced by isoliquiritigenin (ISL). The viability of T24 cells
was estimated using a sulforhodamine B assay. Cell morphological changes were
examined using Hoechst 33258 staining. The apoptotic rate was determined by
staining cells with Annexin V-fluorescein isothiocyanate and propidium iodide
labeling. The mitochondrial membrane potential (DeltaPsim) was measured using
5,5,6,6-tetrachloro-1,1, 3,3-tetraethyl benzimidazole carbocyanine iodide.
Alterations in the apoptosis-related regulators B-cell lymphoma-2 (Bcl-2), Bcl-2
associated X protein (Bax), Bcl-2-interacting mediator of cell death (Bim),
apoptotic protease-activating facter-1 (Apaf-1), caspase-9 and caspase-3 were
determined using reverse transcription-polymerase chain reaction (PCR) and
quantitative PCR methods. Western blot analysis was used to detect the expression
of Bcl-2, Bax and caspase-3. CDK2 activity was measured using a spectrometric
assay. Following treatment with ISL (between 30 and 70 ug/ml) for 24 h, typical
apoptotic morphological changes were observed in T24 cells, exhibiting an edge
set of chromosomes, nuclear condensation, nuclear fragmentation and other
morphological features. Treatment with ISL increased the apoptotic ratio of T24
cells in a concentration-dependent manner and induced a decrease in the DeltaPsim
in a time-dependent manner. Treatment with ISL upregulated the expression of Bax,
Bim, Apaf-1, caspase-9 and caspase-3, downregulated the expression of Bcl-2, and
increased CDK2 activity. MK-8776 (an inhibitor of CDK2) antagonized the apoptosis
induced by ISL, and, compared with treatment with ISL alone, pretreatment with MK
8776 inhibited the decrease in DeltaPsim, downregulated the mRNA expression of
Bax, Bim, Apaf-1, caspase-9 and caspase-3, and upregulated Bcl-2 mRNA expression.
Western blot analysis demonstrated that, with increasing ISL concentration, the
Bcl-2 expression level was significantly decreased (P<0.05), whereas caspase-3
and Bax expression levels were significantly increased (P<0.01). These results
indicated that ISL treatment caused a significant decrease in the proliferation
rate and increase in apoptosis of T24 cells. The mechanism by which ISL induces
T24 cell apoptosis in vitro may be associated with an increase in CDK2 activity,
downregulation of the DeltaPsim and activation of caspase-3/caspase-9-mediated
mitochondrial apoptotic signaling pathways.
PMID- 28693161
TI - PD-L1 and PD-1 expression correlate with prognosis in extrahepatic
cholangiocarcinoma.
AB - The present study aimed to investigate the clinicopathological significance of
programmed cell death ligand-1 (PD-L1) and programmed cell death protein 1 (PD-1)
expression in extrahepatic cholangiocarcinoma (ECC). PD-L1 and PD-1 expression
was detected by immunohistochemical methods in 70 ECC formalin-fixed, paraffin
embedded tissue specimens and 50 para-carcinoma tissue specimens. The
associations of PD-L1 and PD-1 expression with clinicopathological
characteristics and prognosis of ECC patients were explored. Positive rates of PD
L1 and PD-1 expression were increased in ECC tissues compared with those in the
corresponding para-carcinoma tissues. Besides, the expression of PD-L1 was
correlated with the expression of PD-1 (P<0.05). Statistical analysis revealed
that the expression of PD-L1 and PD-1 in ECC tissues exhibited no correlation
with patient age, sex or histological grade, but was significantly correlated
with tumor-node-metastasis (TNM) stage and lymphatic metastasis. Univariate
analysis demonstrated that PD-L1 expression, PD-1 expression, TNM stage and
lymphatic metastasis were significantly associated with the survival time of
patients. Further multivariate analysis revealed the PD-L1 expression was an
independent prognostic factor of patients with ECC. These preliminary results
suggested that PD-L1 or PD-1 immunodetection may be a valuable prognostic marker
for ECC patients, and that PD-L1 immunodetection may be used as an independent
factor to evaluate the prognosis of ECC patients.
PMID- 28693162
TI - Kikuchi-Fujimoto disease in the regional lymph nodes with node metastasis in a
patient with tongue cancer: A case report and literature review.
AB - Kikuchi-Fujimoto disease (KFD), also known as histiocytic necrotizing
lymphadenitis, is a rare self-limiting disorder typically affecting the cervical
lymph nodes (LNs), which is often misdiagnosed as other LN-associated diseases.
KFD frequently presents with necrotic lesions and recurrences, which are also
features of metastatic LNs. Clinicians may thus suspect LN metastasis when they
encounter ipsilateral cervical lymphadenopathy in a patient with head and neck
cancer. The present study reports the case of a 48-year-old man with tongue
cancer and KFD affecting the right edge of his tongue and ipsilateral cervical
LNs. LN metastasis was initially suspected, but pathological examination of the
dissected LNs revealed one necrotic metastatic lesion and two necrotic KFD
lesions. Ipsilateral cervical lymphadenopathy recurred 6 years after the initial
surgery, and it was not possible to differentiate clinically between a second
primary tumor and recurrent KFD prior to treatment. To the best of our knowledge,
this is the first reported case of simultaneous tongue cancer, regional LN
metastasis and KFD. This highlights the requirement to consider KFD in the event
of LNs with necrotic lesions but no cancerous cells. A combination of clinical
and pathological approaches may aid in the diagnosis of KFD, in addition to
ruling out LN metastasis in initial and recurrent lymphadenopathies. The present
study indicate that a diagnosis of KFD should be considered in patients with head
and neck cancer that exhibit necrotic LNs lacking cancerous cells. This is
important, as misdiagnosis of KFD as LN metastasis may lead to unnecessary
adjuvant therapy.
PMID- 28693163
TI - Monocyte chemoattractant protein 1 expression and proliferation in primary
central nervous system lymphoma.
AB - Whether the poor prognosis of primary central nervous system lymphoma (PCNSL)
compared with systemic diffuse large B cell lymphoma (DLBCL) is attributable to
the immune privilege of the intracerebral location or to intrinsic differences in
the biological characteristics of two types of lymphoma remains unclear. Monocyte
chemoattractant protein 1 (MCP-1) is essential to support tumor cell survival and
growth, and the present study aimed to compare MCP-1 expression in PCNSL and
peripheral DLBCL. The present study included 19 patients with PCNSL and 16
patients with DLBCL, all of whom had tissue diagnosis and lymphoma tissue samples
available for analysis. Histology included immunohistochemistry using antibodies
against a panel of lymphoma markers, antibodies specific to MCP-1, and antibodies
specific to tumor-associated macrophages. MCP-1 expression was quantified using
immunostaining scoring. RNA extraction and reverse transcription-quantitative
polymerase chain reaction were used to determine MCP-1 mRNA expression. In
addition, a human brain-derived lymphoma cell line, HKBML, was stimulated with
MCP-1 and cell proliferation was measured by 5-bromo-2'-deoxyuridine
incorporation. The expression levels of MCP-1 mRNA and MCP-1 protein were
significantly increased in PCNSL compared with peripheral DLBCL. MCP-1 induced
tyrosine phosphorylation of mitogen-activated protein kinase in HKBML cells, as
analyzed by western blotting. The results of the present study indicated that MCP
1 expression in PCNSL promoted cell proliferation in an autocrine manner.
PMID- 28693164
TI - Correlation study of DNA methylation of WNT6 gene with osteosarcoma in children.
AB - The aim of this study was to evaluate the status and explore the impact of DNA
methylation of WNT6 gene with osteosarcoma in children. A total of 50 patients
with primary osteosarcoma in children were enrolled. The expression of WNT6
protein was determined by immunohistochemical staining. The DNA methylation level
of WNT6 gene was evaluated by methylation-specific PCR (MSP). Human MG63
osteosarcoma cells and human normal Hfob1.19 osteoblasts were selected and
cultured. Western blot analysis was utilized to measure the expression of WNT6 in
the two cell lines. MSP was used to assess the status of DNA methylation of WNT6
gene. The correlation between DNA methylation of WNT6 gene and prognosis of
osteosarcoma in children was evaluated by statistical analysis of the clinical
and prognostic data. The results of the immunohistochemical assay showed that 84%
(42/50) of primary osteosarcoma was WNT6 positive. MSP indicated that DNA
methylation of WNT6 gene was found in 9 cases (18%) of primary osteosarcoma.
Western blot analysis showed that WNT6 protein expression in MG63 cells was
significantly higher than that in normal human Hfob1.19 osteoblasts, whereas, the
level of DNA methylation of WNT6 gene in MG63 cells was significantly lower than
in Hfob1.19 cells. Analysis of survival, prognosis and their correlation found
that the DNA methylation level of WNT6 gene was negatively correlated with the
prognosis of children with osteosarcoma. In conclusion, there was a high level of
WNT6 gene expression in primary osteosarcoma, which was mainly due to low DNA
methylation level of WNT6 gene. The DNA methylation of WNT6 gene was negatively
correlated with the prognosis of patients with osteosarcoma in children.
PMID- 28693165
TI - The enhanced tumor inhibitory effects of gefitinib and L-ascorbic acid
combination therapy in non-small cell lung cancer cells.
AB - Despite documentation of successful therapy with epidermal growth factor receptor
(EGFR) tyrosine kinase inhibitors in patients with lung cancer, the response rate
of patients treated with this therapy remains low. The present study investigated
whether L-ascorbic acid serves an adjuvant role in vitro when combined with the
EGFR tyrosine kinase inhibitor gefitinib (Iressa(r)) in lung cancer cell lines. A
total of three human lung cancer cell lines were used. The antiproliferative
effects and changes in the cell cycle and expression of intracellular signaling
molecules, including extracellular signal-regulated kinases (Erk), signal
transducer and activator of transcription 3 (Stat3) and protein kinase B (Akt),
were measured in cells treated with gefitinib and/or L-ascorbic acid at various
concentrations. When combined with gefitinib, L-ascorbic acid exhibited an
additive effect on cell proliferation in all gefitinib-sensitive and gefitinib
resistant cell lines. A decrement of ~40% was observed with a low dose 0.5 mM L
ascorbic acid and gefitinib in the relatively gefitinib-resistant A549 cell line
(85.6+/-5.4% with gefitinib alone vs. 52.7+/-7.3% with combination therapy;
P=0.046). The downregulation of intracellular signaling cascades, including EGFR,
Akt, Erk and Stat3, was also observed. L-Ascorbic acid serves an adjuvant role
when administered in combination with gefitinib; however, the degree of
inhibition of cell proliferation differs between lung cancer cell lines.
PMID- 28693166
TI - Quantitative analysis and clonal characterization of T-cell receptor beta
repertoires in patients with advanced non-small cell lung cancer treated with
cancer vaccine.
AB - With the development of cancer immunotherapy that may activate T cells, a
practical and quantitative method to improve monitoring and/or prediction of
immunological response of patients as a predictive biomarker is of importance. To
examine possible biomarkers for a therapeutic cancer vaccine containing a mixture
of three epitope peptides derived from cell division-associated 1, lymphocyte
antigen 6 complex locus K and insulin-like growth factor-II mRNA-binding protein
3, T-cell receptor beta (TCRbeta) repertoires of blood samples from 24 patients
with human leukocyte antigen-A*2402-positive non-small cell lung cancer were
characterized prior to and following 8 weeks of the cancer vaccine treatment, by
applying a next-generation sequencing method. It was identified that 14 patients
with overall survival (OS) times of >=12 months had significantly lower TCRbeta
diversity indexes in samples prior to treatment, compared with 10 patients who
succumbed within 1 year (P=0.03). In addition, patients with a high level of
activated CD8+ T cells that are defined by a high granzyme A/CD8 ratio had
favorable OS rates (log-rank test, P=0.04). The TCRbeta diversity index and
immunogenic gene markers following vaccine administration may serve as predictive
or monitoring biomarkers for cancer vaccine treatment.
PMID- 28693167
TI - Glasgow prognostic score predicts therapeutic outcome after hepatic resection for
hepatocellular carcinoma.
AB - Systemic inflammation, as evidenced by the Glasgow prognostic score (GPS),
predicts cancer-specific survival in various cancer types. The aim of this study
was to evaluate the significance of the GPS in the therapeutic outcome of the
patient following surgical resection for hepatocellular carcinoma. In total, 144
patients underwent surgical resection for hepatocellular carcinoma. For the
assessment of systemic inflammatory response using the GPS, patients were
classified into three groups: Patients with normal serum albumin (<3.5 g/dl) and
normal serum C-reactive protein (CRP) (<=1.0 mg/dl) were classified as GPS 0
(n=76), those with low serum albumin (<3.5 g/dl) or elevated serum CRP (>1.0
mg/dl) were classified as GPS 1 (n=58), and those with low serum albumin (<3.5
g/dl) and elevated serum CRP (>1.0 mg/dl) were classified as GPS 2 (n=10).
Retrospectively, the relationship between patient characteristics including GPS,
disease-free as well as overall survival were investigated. In disease-free
survival, GPS 2 (P=0.019), with a tumor number >=3 (P=0.004), and positive portal
or venous invasion (P=0.034) were independent predictors of cancer recurrence in
multivariate analysis. In overall survival, GPS 1 (P=0.042), GPS 2 (P<0.001) and
positive portal or venous invasion (P<0.001) were independent predictors of poor
patient outcome according to multivariate analysis. To conclude, the GPS in
patients with hepatocellular carcinoma is an independent prognostic predictor
after hepatic resection.
PMID- 28693168
TI - A comparison of clinicopathological features and prognosis in prostate cancer
between atomic bomb survivors and control patients.
AB - An atomic bomb (A-bomb) was dropped on Hiroshima on 6th August 1945. Although
numerous studies have investigated cancer incidence and mortality among A-bomb
survivors, only a small number have addressed urological cancer in these
survivors. The aim of the present study was to investigate the
clinicopathological features of prostate cancer (PCa) in A-bomb survivors. The
clinicopathological features and prognosis of PCa were retrospectively reviewed
in 212 survivors and 595 control patients between November 1996 and December
2010. The histopathological and clinical outcomes of surgical treatment of PCa
were also evaluated in 69 survivors and 162 control patients. Despite the higher
age at diagnosis compared with the control group (P=0.0031), survivors were more
likely to have been diagnosed with PCa from a health check compared with the
control group (P<0.0001). As a consequence, the survivors were found to exhibit
metastasis significantly less frequently (199/212, 93.9%) compared with the
control patients (521/595, 87.6%; P=0.0076). Prognosis in the two groups was
examined, subsequent to a mean length of follow-up of 44 months. Overall survival
(OS) and PCa-specific survival (CS) were similar between the two groups (OS,
P=0.2196; CS, P=0.1017). A-bomb exposure was not found to be an independent
predictor for prognosis by multivariate analysis (OS, P=0.7800; CS, P=0.8688).
The clinicopathological features of patients who underwent a prostatectomy were
similar except for the diagnosis opportunity between the two groups. Progression
free survival rates were similar between the two groups (P=0.5630). A-bomb
exposure was not a significant and independent predictor for worsening of
progression-free prognosis by multivariate analysis (P=0.3763). A-bomb exposure
does not appear to exert deleterious effects on the biological aggressiveness of
PCa and the prognosis of patients with PCa.
PMID- 28693169
TI - Evaluation of erlotinib for the treatment of patients with non-small cell lung
cancer with epidermal growth factor receptor wild type.
AB - Erlotinib is one of the treatment choices for patients with advanced non-small
cell lung cancer (NSCLC), regardless of the epidermal growth factor receptor
(EGFR) mutation status. However, its efficacy for the treatment of patients with
NSCLC with EGFR wild type or who are beyond the usage of gefitinib remains
controversial. The present study therefore retrospectively assessed the efficacy
of erlotinib in patients with wild type EGFR who had previously undergone
gefitinib therapy. A total of 222 patients with NSCLC who received
chemotherapeutic treatment with erlotinib between July 2007 and February 2013
were evaluated. The background variables, response rates, progression-free
survival (PFS) and overall survival rates were retrospectively analyzed. The
male/female ratio of patients was 103/119, and patients had a median age of 63
years (range, 33-95 years). A total of 10 of the 222 patients had clinical stages
IIIB/IV, 191 had adenocarcinoma, 5 had large cell carcinoma, 10 had squamous cell
carcinoma and 6 had NSCLC of a variety not otherwise specified. The EGFR mutation
was positive, wild type or unknown in 95, 52 and 75 patients, respectively. In
the 52 patients with EGFR wild type, there were 3 partial responders, 25 with
stable disease and 24 with progressive disease, for a response rate of 6% [95%
confidence interval (CI), 1.3-15%]. The median PFS of EGFR wild type and positive
were 1.1 months (95% CI, 1.04-1.16 months) and 5.42 months (95% CI, 5.43-5.68
months), respectively. The results of the study demonstrated that erlotinib is
not sufficiently effective for patients with NSCLC who possess the EGFR wild type
status.
PMID- 28693170
TI - Prognostic significance of ABCB1 in stage I lung adenocarcinoma.
AB - Cancer stem cell (CSC) properties have been recently proposed to explain tumor
carcinogenesis and multidrug resistance in several human cancers, including non
small cell lung cancer (NSCLC). The present study examined the protein expression
of three CSC-associated markers, namely ATP binding cassette subfamily B member 1
(ABCB1), aldehyde dehydrogenase 1 family member A1 (ALDH1A1) and cluster of
differentiation (CD) 44, by immunohistochemistry in 194 NSCLC patients who
underwent complete resection of NSCLC tumors. The association between the
expression of these proteins and patient prognosis was evaluated to clarify the
prognostic significance of CSC-associated markers in NSCLC patients. Positive
staining for ABCB1 demonstrated a trend toward worse survival compared with
negative staining in stage I-III NSCLC. Negative staining for ALDH1 or CD44
exhibited a trend toward worse survival compared with positive staining in stage
I-III NSCLC. It was observed that patients with stage I lung adenocarcinoma (ADC)
showing positivity for ABCB1 expression had significantly poorer survival than
those with negative ABCB1 staining (P=0.03). Furthermore, stage I ADC patients
with wild-type epidermal growth factor receptor (EGFR) who exhibited positive
staining for ABCB1 had significantly shorter disease-free survival (DFS) compared
with patients with negative staining for ABCB1 (P<0.01). Analyses by univariate
and multivariate Cox proportional hazards models revealed that ABCB1-positive
staining was significantly associated with DFS and was an independent prognostic
factor (hazard ratio, 3.49; P<0.05) in these patients. These results suggest that
ABCB1 protein expression is useful for predicting prognosis and selecting
patients for post-operative therapy in stage I lung ADC patients, particularly
those harboring wild-type EGFR.
PMID- 28693171
TI - Temozolomide induces autophagy in primary and established glioblastoma cells in
an EGFR independent manner.
AB - Despite major contributions to the current molecular understanding of autophagy,
a recycling process for intracellular components to maintain homeostatic balance,
relatively little is known about the interacting networks. To address this issue,
the current study investigated the role of autophagy in primary and established
glioblastoma multiforme (GBM) cells and its interplay with the epidermal growth
factor receptor (EGFR) and the standard chemotherapeutic agent temozolomide
(TMZ). TMZ treatment leads to an upregulation of autophagy, predominantly in
primary GBM cells. The interaction between EGFR and Beclin-1, an important
protein in initiating autophagy, was assessed using a cancer cell line
transfected with EGFRvIII, and by stimulation with EGF. The results of the
current study suggest that Beclin-1 and EGFR do not interact directly in either
primary or established GBM cells. To enable the limited efficacy of patient
treatment strategies of GBM to potentially be enhanced through the application of
autophagy regulators, the multiple cellular interactions of autophagy require
further elucidation.
PMID- 28693172
TI - Silencing platelet-derived growth factor receptor-beta enhances the
radiosensitivity of C6 glioma cells in vitro and in vivo.
AB - Platelet-derived growth factor receptor (PDGFR)-beta is an important tyrosine
kinase and its downregulation has been reported to alter the radiosensitivity of
glioma cells, although the underlying mechanism is unclear. In order to
investigate the effect of PDGFR-beta on the radiosensitivity of glioblastoma, the
present study transfected C6 glioma cells with a PDGFR-beta-specific small
interfering (si)RNA expression plasmid, and downregulation of the expression of
PDGFR-beta in C6 glioma cells was confirmed by western blotting and
immunohistochemical analysis. Clone formation assays and xenograft growth curves
demonstrated that PDGFR-beta-siRNA enhanced the radiosensitivity of C6 glioma
cells in vitro and in vivo. Furthermore, MTT and xenograft growth curves
demonstrated that PDGFR-beta-siRNA inhibited the proliferation of C6 glioma cells
in vitro and in vivo, and terminal deoxynucleotidyl transferase dUTP nick end
labeling and immunohistochemical analyses demonstrated that PDGFR-beta-siRNA
induced apoptosis and inhibited the expression of Ki-67, cyclin B1 and vascular
endothelial growth factor in C6 glioma cell xenografts. Taken together, these
results suggested that PDGFR-beta may be used as a target for the
radiosensitization of glioblastoma.
PMID- 28693173
TI - Predictive and prognostic significance of CD8+ tumor-infiltrating lymphocytes in
patients with luminal B/HER 2 negative breast cancer treated with neoadjuvant
chemotherapy.
AB - The immunobiology of breast cancer (BC) subtypes, including luminal cancer,
remains unclear. Cluster of differentiation (CD)8+ tumor-infiltrating lymphocytes
(TIL) are essential components of tumor-specific cellular adaptive immunity.
However, only few studies have addressed the significance of cluster of
differentiation 8+(CD8+) TIL in patients with luminal BC. The present study aimed
to evaluate the predictive and prognostic significance of CD8+ TIL in patients
with luminal B/human epidermal growth factor receptor 2 (HER 2)-negative BC
treated with anthracycline-based neoadjuvant chemotherapy (NC). A total of 31
patients who underwent breast-conserving surgery or mastectomy post-NC were
enrolled. Immunostaining for CD8+ TIL was performed using rabbit monoclonal
antibodies against human CD8+. Intra- and peritumoral CD8+ TIL expression levels
were classified into high and low, based on the median value of each. CD8+ TIL
expression data were demonstrated to be correlated with disease-free survival
(DFS) and overall survival (OS), using Kaplan-Meier and Cox's proportional
hazards regression tests. The results revealed that, among all
clinicopathological characteristics, only pathological complete response (pCR)
was significantly correlated with intratumoral CD8+ TIL expression (P=0.016). A
total of 9/16 patients (56%) with high intratumoral CD8+ TIL expression achieved
pCR, in contrast with 2 out of 15 patients (13.3%) with low expression (P=0.016).
High expression of intratumoral CD8+ TIL was significantly associated with OS
(log-rank test, P=0.023). Multivariate Cox regression analysis revealed that
intratumoral expression of CD8+ TIL was an independent prognostic factor for OS
[hazard ratio (HR)=2.82; 95% confidence interval (CI)=0.911-4.833, P=0.007], but
not for DFS (HR=1.11; 95% CI=0.282-2.078; P=0.508). In conclusion, the results of
the present study suggested that high intratumoral CD8+ TIL expression was
significantly predictive of pCR post-NC, and represented an independent
prognostic factor for improved OS. In contrast, low intratumoral CD8+ TIL
expression was a strong predictor of lack of pCR to NC, as well as an independent
prognostic factor for poor OS. Assessment of the immune response in conjunction
with the usual parameters may aid in the further stratification of patients with
luminal B/HER 2-negative BC regarding the prediction of pCR post-NC and overall
prognosis.
PMID- 28693174
TI - BRCA1 expression serves a role in vincristine resistance in colon cancer cells.
AB - The present study aimed to investigate the association between breast cancer
susceptibility gene 1 (BRCA1) expression and drug resistance in colon cancer,
with the specific aim of elucidating the underlying molecular mechanisms of
vincristine (VCR) resistance in tumor cells. The HCT-8 human colon cancer cell
line was used to establish the VCR-resistant HCT-8/V line by gradually increasing
the concentration of VCR during cell culture. The relative mRNA and protein
expression levels of BRCA1 in these colon cancer cell lines was assessed by
reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) analysis
and western blotting, respectively. Resistance to VCR was established in the HCT
8/V colon cancer cells, and RT-qPCR and western blot analysis revealed the
expression of BRCA1 to be significantly higher in the VCR-resistant cells
compared with their drug-sensitive counterparts (P<0.05). The decreased BRCA1
expression in these VCR-resistant cells may be associated with the drug
resistance frequently observed in colon cancer.
PMID- 28693175
TI - Functional analysis of CD14+HLA-DR-/low myeloid-derived suppressor cells in
patients with lung squamous cell carcinoma.
AB - Immunomodulatory therapy is a potential effective treatment for advanced cancer
that may provide an alternative to chemotherapy, which patients can experience
adverse side effects to. Myeloid-derived suppressor cells (MDSCs) have been
demonstrated to cause T-cell tolerance in rodents and humans; however, little is
known about the role of MDSCs in squamous cell carcinoma. In the present study,
the role of MDSCs in lung squamous cell carcinoma was investigated. Peripheral
blood from 78 patients with lung squamous cell carcinoma and 30 healthy controls
was examined for the presence and function of human MDSCs, denoted as monocyte
differentiation antigen CD14-positive HLA class II histocompatibility antigen DR
negative/low (CD14+ HLA-DR-/low) cells by flow cytometry. The sorted T-cell
surface glyoprotein CD3 (CD3)+ cells and CD14+HLA-DR-/low cells were subsequently
co-cultured with a tumor cell line (NCI-H226). T-cell apoptosis was detected
using annexin-V-fluorescein isothicyanate and 7-aminoactinomycin D. Interferon
gamma (IFN-gamma) levels were detected using an ELISA. The frequency of MDSCs in
the peripheral blood mononuclear cells (PBMCs) from patients with lung squamous
cell carcinoma was significantly higher compared with that of the healthy
controls (P<0.05), whereas the frequency of T-cell surface glyoprotein CD4 (CD4)+
T cells and CD8+ T cells in PBMCs was significantly decreased (P<0.05). In an
MDSC/CD8+ co-culture system, the proportion of CD8+ T-cell apoptosis
significantly increased with the increase in ratio of MDSCs (P<0.05), while the
proportion of tumor cell apoptosis significantly decreased (P<0.05). The
concentration of IFN-gamma significantly decreased with the increase in MDSCs
(P<0.05). Therefore, MDSCs participate in the immune escape of lung squamous cell
carcinoma, and may provide a possible therapeutic strategy for the treatment of
this disease.
PMID- 28693176
TI - Flexible magnifying endoscopy with narrow band imaging for the diagnosis of
uterine cervical tumors: A cooperative study among gastrointestinal endoscopists
and gynecologists to explore a novel microvascular classification system.
AB - Narrow band imaging with magnifying endoscopy (NBI-ME), which is useful for the
assessment of micro-vessels, has excellent diagnostic potential for early
gastrointestinal epithelial neoplasia. Conventional diagnostic tools for uterine
cervical epithelial tumors are still unsatisfactory. An accurate diagnostic tool
for uterine cervical epithelial tumors is required to preserve the reproductive
ability of young women with uterine cervical tumors. Flexible NBI-ME was
performed in patients with cervical squamous cell lesions that required further
examinations based on their Pap smear results (cytology >= low-grade squamous
intraepithelial lesion) at Kagawa University Hospital between April 2014 and
April 2015. NBI-ME results concordant with the punch biopsy sites were compared
with the histological results. A retrospective review of the NBI-ME images
identified abnormal NBI-ME results regarding micro-vascular patterns. All images
were categorized as having abnormal features. NBI-ME revealed the following
vascular pattern differences of different stage tumors: Dot-like vessels without
irregular arrangements and high density in cervical intraepithelial neoplasia
(CIN) CIN1-CIN2; dot-like vessels with irregular arrangements and high density in
CIN3-carcinoma in situ; crawling vessels in minimum invasive cancer; and willow
branch vessels and new tumor vessels in invasive cancer. NBI-ME may be an
effective diagnostic tool for uterine cervical epithelial tumors, which may lead
to the establishment of a novel classification system.
PMID- 28693177
TI - Low expression of microRNA-30c promotes prostate cancer cells invasion involved
in downregulation of KRAS protein.
AB - Aberrant microRNA expression is associated with tumor development. The present
study aimed to elucidate the role of miR-30c in the development of prostate
cancer. Quantitative polymerase chain reaction was performed to compare miR-30c
expression in LNCaP, DU145, PC-3 and RWPE-1 cell lines. Lentivirus expressing miR
30c was used to create stable overexpression cell lines to investigate the
effects of miR-30c overexpression on cell proliferation, migration and invasion,
which were determined in the prostate cancer cell line PC-3 by MTT, colony
formation, wound healing and Transwell assays. Effects of miR-30c on KRAS were
examined by western blot analysis. miR-30c expression was significantly lower
(P<0.05) in the PC-3 cell line compared with LNCaP, DU145 and RWPE-1 cell lines.
miR-30c overexpression in PC-3 inhibited tumor cell proliferation, migration and
invasion in vitro. Furthermore, KRAS protein expression was downregulated in miR
30c overexpression cell lines compared with the negative control (NC) group
(P<0.05). The present results demonstrated that overexpression of miR-30c
inhibits prostate cancer cell line proliferation, migration and invasion, which
was possibly caused by downregulation of KRAS protein by miR-30c. The data
implicate miR-30c in the prognosis and treatment of prostate cancer.
PMID- 28693178
TI - Presurgical neoadjuvant targeted molecular therapy for kidney cancer with
concomitant vena cava tumor embolus: A clinical study.
AB - The present study aimed to investigate presurgical neoadjuvant targeted therapy
for patients with kidney cancer and vena cava tumor embolus, in order to examine
its indications, therapeutic effects and optimal timing of surgery. Between June
2009 and June 2014, 12 patients from The People's Liberation Army General
Hospital (Beijing, China) were diagnosed with kidney cancer with superior vena
cava tumor embolus, and received presurgical neoadjuvant targeted therapy
(sorafenib 400 mg twice a day or sunitinib 50 mg/day) for a median of 13.3 weeks.
Patients included 8 males and 4 females, with a median age of 49.8 years. Kidney
cancer was present on the left side in 3 patients and in the right side in 9
patients. The median tumor embolus length was 9.7 cm (range, 6.5-14.0 cm). Tumor
embolus levels II, III and IV, classified by the Mayo Clinic standard, were
observed in 2, 6 and 4 patients, respectively. Median treatment time and average
targeted therapy discontinuation time were observed to be longer in sunitinib
treated patients compared with sorafenib-treated patients. In total, 2 patients
in the present study had partial remission (PR) and 8 patients had stable disease
(SD); for tumor embolus, 4 patients had PR and 8 patients had SD. Tumor embolus
length decreased by a median value of 18.7% (range, 0.0-42.1%) or 1.8 cm (range,
0.1-5.2 cm). Tumor diameter decreased by a median value of 8.6% (range, 0.0
38.9%) or 0.7 cm (range, 0.0-3.5 cm). The level of the tumor thrombus, classified
by the Mayo Clinic standard, was observed to decrease following sunitinib
treatment, including two cases downgraded from tumor thrombus level IV to II, one
case from level IV to III and two cases from level III to II. Presurgical
neoadjuvant targeted molecular therapy may have the potential to reduce the tumor
stage of patients, as well as decreasing the surgical difficulty for radical
nephrectomy.
PMID- 28693179
TI - Association between periostin and epithelial-mesenchymal transition in esophageal
squamous cell carcinoma and its clinical significance.
AB - The present study aimed to investigate the association between periostin (POSTN),
epithelial cadherin (E-cad) and vimentin (Vim) expression levels in esophageal
squamous cell carcinoma (ESCC) tissues, and its clinicopathological significance.
A total of 58 patients with esophageal cancer were enrolled. Immunohistochemistry
was performed to quantify the expression levels of POSTN, E-cad and Vim. E-cad
expression was reduced in ESCC tissue, which was associated with severe tumor
node metastasis (TNM) stage (P<0.001), lymphatic metastasis (P<0.001) and
vascular invasion (P=0.026). Conversely, Vim expression was found to be increased
in ESCC tissues, and had associations with TNM stage (P=0.039) and lymphatic
metastasis (P=0.039). POSTN overexpression observed in ESCC cells was associated
with attenuation of E-cad expression (P<0.001) and elevated expression levels of
Vim (P<0.001). Additionally, significant correlations between the overexpression
of POSTN in ESCC cells and clinicopathological variables including TNM staging
(P=0.009), degree of differentiation (P<0.001), lymphatic metastasis (P=0.009)
and vascular invasion (P=0.002) were verified. Multivariate analysis revealed
that overexpression of POSTN in ESCC cancer cells is able to predict the poor
prognosis of patients independently of overall survival (P=0.022) and disease
free survival (P=0.019). The preliminary findings of the present study
demonstrate that POSTN is involved in the epithelial-mesenchymal transition of
ESCC cells, and may therefore be a predictive factor for tumor invasion and
metastasis, as well as an indicator of poor prognosis for patients with ESCC.
PMID- 28693180
TI - Soluble urokinase-type plasminogen activator receptor and urokinase-type
plasminogen activator receptor contribute to chemoresistance in leukemia.
AB - The soluble urokinase-type plasminogen activator receptor (suPAR) and the
urokinase-type plasminogen activator receptor (uPAR) have been proposed as useful
biomarkers of tumor progression. Recently, suPAR was associated with
chemoresistance in lung cancer. However, its clinical significance in leukemia
has not previously been investigated. The present study examined the plasma
levels of suPAR and the expression of the uPAR on bone marrow (BM) cells in 86
patients with leukemia at diagnosis prior to chemotherapy and 26 normal subjects
(control group). The plasma suPAR levels were measured using ELISA, whilst uPAR
expression was assayed by flow cytometry analysis. In addition, cell surface uPAR
expression on K562 and multidrug-resistant K562/ADM cell lines was studied by
western blotting. On admission and follow-up, the levels of suPAR in patients
with leukemia were significantly increased compared with controls. Systemic
levels of suPAR were strongly associated with the numbers of white blood cells. A
case was defined as uPAR-positive (uPAR+) if >20% of the gated cells expressed
uPAR. In comparison with 26 healthy BM samples that were negative for uPAR
expression, 48 (55.8%) of the 86 leukemia patients were uPAR+. uPAR expression on
the cell surface of multidrug-resistant K562/ADM cells was increased compared
with that on K562 cells. In conclusion, plasma suPAR expression may be a useful
marker for subtype classification of patients with leukemia and cell surface uPAR
may be associated with resistance to chemotherapy or disease progression.
PMID- 28693181
TI - Distinct DNA methylation alterations are associated with cribriform architecture
and intraductal carcinoma in Gleason pattern 4 prostate tumors.
AB - The aim of the present study was to explore DNA methylation aberrations in
association with cribriform architecture and intraductal carcinoma (IDC) of the
prostate, as there is robust evidence that these morphological features are
associated with aggressive disease and have significant clinical implications.
Herein, the associations of a panel of seven known prognostic DNA methylation
biomarkers with cribriform and IDC features were examined in a series of 91
Gleason pattern (GP) 4 tumors derived from Gleason score 7 radical
prostatectomies. Gene specific DNA methylation was compared between cribriform
and/or IDC positive vs. negative cases, and in association with
clinicopathological features, using Chi square and Mann-Whitney U tests. DNA
methylation of the adenomatous polyposis coli, Ras association domain family
member 1 and T-box 15 genes was significantly elevated in GP4 tumors with
cribriform and/or IDC features compared with negative cases (P=0.045, P=0.007 and
P=0.013, respectively). To the best of our knowledge, this provides the first
evidence for an association between cribriform and/or IDC and methylation
biomarkers, and warrants further investigation of additional DNA methylation
events in association with various architectural patterns in prostate cancer.
PMID- 28693182
TI - Location of the meso-pancreatoduodenum as a regional lymphatic basin for
pancreatic head carcinoma.
AB - The meso-pancreatoduodenum is the primary site of tumor infiltration in patients
with pancreatic head cancer, with numerous patients exhibiting lymph node
metastases. Effective dissection of the regional lymphatic basin requires
knowledge of the patterns of the arterial branches. The present study examined
the patterns of the arteries feeding the pancreatic head and the distribution of
the meso-pancreatoduodenum. The present study included 123 patients with
pancreatic cancer who underwent contrast-enhanced preoperative 64-multidetector
computed tomography to determine the routes of the inferior pancreaticoduodenal
and first jejunal arteries. Surgical specimens and cadavers were also evaluated
histologically to clarify the distribution of the meso-pancreatoduodenum. The
feeding arteries were divided into three types, with 64.2% of patients having
type A, 28.4% having type B and 7.3% having type C branches. The branches emerged
from the back or left side of the superior mesenteric artery and ran to the far
side of the pancreatic head in an arc. Consequently, the meso-pancreatoduodenum
had a roll-shaped appearance, surrounding the trunk arteries and extending to the
left side of the superior mesenteric artery. Dissecting the right and left sides
of the superior mesenteric artery during lymphadenectomy could improve the
effectiveness of resection.
PMID- 28693183
TI - High expression of P21-activated kinase 5 protein is associated with poor
survival in gastric cancer.
AB - P21-activated kinase 5 (PAK5), also termed PAK7, is one of the six members of the
PAK family of serine/threonine kinases, which are downstream effectors in several
cancer signaling pathways. PAK5 promotes neural outgrowth, contributes to
microtubule stability and induces resistance to apoptosis. However, the clinical
importance of PAK5 in gastric cancer has not been comprehensively investigated.
In the present study, PAK5 expression was evaluated in gastric cancer tissue
samples. Furthermore, the associations between high expression of PAK5, and
clinicopathological features and prognosis were examined. PAK5 expression in
primary gastric cancer specimens resected from 279 patients who underwent
gastrectomy at the Tokyo Medical and Dental University Hospital was evaluated
using immunohistochemistry. Of the 279 patients, 44 (15.8%) exhibited high PAK5
expression, which was significantly associated with the differentiated
pathological type (differentiated vs. undifferentiated; P<0.001), depth of tumor
invasion (T1 vs. T2-T4; P<0.001), lymph node metastasis (N0 vs. N1-N3; P<0.001),
presence of distant metastasis or recurrence (present vs. absent; P=0.038),
advanced tumor stage (I vs. II-IV; P=0.001) and worse disease-specific survival
(P=0.013). In stage I-III disease, 38/254 (15.0%) patients exhibited high PAK5
expression, and high expression of PAK5 was significantly associated with relapse
free interval (P=0.044). PAK5 may serve an important role in tumor progression
and influence the outcome of patients with gastric cancer.
PMID- 28693184
TI - Expression of autophagy-associated proteins in papillary thyroid carcinoma.
AB - The present study was designed to assess the protein expression of the autophagy
associated genes, Beclin-1 and microtubule-associated protein 1 light chain 3
(LC3)-II, as well as the association with clinicopathological features in
papillary thyroid carcinoma (PTC). A total of 50 subjects were recruited,
including 50 human PTC samples and paired adjacent noncancerous tissue samples.
The protein expression of Beclin-1 and LC3-II was analyzed using
immunohistochemistry and western blotting. Beclin-1 and LC3-II expression in PTC
tissues significantly reduced compared with normal tissues (P<0.05). Expression
of Beclin-1 and LC3-II was associated with lymph node metastasis of PTC (P<0.05),
but had no association with age, gender, tumor size, tumor number and Tumor-Node
Metastasis stage (P>0.05). Expression of Beclin-1 and LC3-II were positively
correlated (r=0.327;P=0.020) in PTC. In conclusion, the activity of autophagy was
declined in PTC; this decrease in autophagic capacity may be associated with
tumorigenesis and the development of PTC.
PMID- 28693185
TI - Withaferin A inhibits the proliferation of gastric cancer cells by inducing G2/M
cell cycle arrest and apoptosis.
AB - Human gastric adenocarcinoma (AGS) is one of the most common types of malignant
tumor and the third-leading cause of tumor-associated mortality worldwide.
Withaferin A (WA), a steroidal lactone derived from Withania somnifera, exhibits
antitumor activity in a variety of cancer models. However, to the best of our
knowledge, the direct effect of WA on AGS cells has not previously been
determined. The present study investigated the effects of WA on the proliferation
and metastatic activity of AGS cells. WA exerted a dose-dependent cytotoxic
effect on AGS cells. The effect was associated with cell cycle arrest at the G2/M
phase and the expression of apoptotic proteins. Additionally, WA treatment
resulted in a decrease in the migration and invasion ability of the AGS cells, as
demonstrated using a wound healing assay and a Boyden chamber assay. These
results indicate that WA directly inhibits the proliferation and metastatic
activity of gastric cancer cells, and suggest that WA may be developed as a drug
for the treatment of gastric cancer.
PMID- 28693186
TI - Cholangiocarcinoma following external beam radiotherapy: A report of two cases.
AB - Cholangiocarcinoma (CCA) is a relatively rare primary malignancy, with
established risk factors that include primary sclerosing cholangitis, choledochal
cysts and hepatolithiasis. In the present study, two cases of CCA, which occurred
following abdominal external beam radiotherapy (EBRT) for non-Hodgkin's lymphoma,
are reported. Case 1 and 2 were diagnosed with cholangiocarcinoma 30 and 4 years
following treatment with combined chemotherapy and abdominal radiotherapy
treatment, respectively. The patients received chemotherapy as treatment of
cholangiocarcinoma; however, whilst their symptoms improved, they succumbed
within 12 and 2 months respectively following the diagnosis with
cholangiocarcinoma. Currently, the association between radiation exposure and
hepatobiliary malignancy remains unclear, however, we hypothesize that biliary
epithelium sensitivity to ionizing radiation may have contributed to the etiology
of the secondary malignancies observed in these two patients. This study
indicates that patients treated with abdominal EBRT may benefit from a heightened
index of suspicion and more intensive surveillance for secondary biliary
malignancies.
PMID- 28693187
TI - Salinomycin inhibits canine mammary carcinoma in vitro by targeting cancer stem
cells.
AB - Salinomycin (SAL), a polyether ionophore antibiotic, has been demonstrated to
selectively kill cancer stem cells (CSCs) in various types of human tumor. The
aim of the present study was to investigate the effects of SAL on canine mammary
CSCs. CSCs in canine mammary carcinoma cell lines (CMT7364 and CIPp) were
identified using a sphere formation assay and flow cytometry. The
chemoresistance, invasive potential and expression of stem cell-associated
proteins of these spheres was then analyzed. This demonstrated that the spheres
exhibited characteristics of CSCs, including a cluster of differentiation
(CD)44+/CD24-/low phenotype, upregulation of Wnt/beta-catenin signaling pathway
associated proteins and chemoresistance. The viability of the spheres was
decreased in a concentration- and time-dependent manner following treatment with
SAL, and the spheres did not exhibit increased resistance to SAL compared with
their parental cells. In addition, exposure to SAL inhibited sphere-formation and
invasive potential in canine mammary CSCs in a dose-dependent manner.
Furthermore, SAL decreased the CD44+/CD24-/low population and downregulated the
expression of Wnt/beta-catenin signaling-associated proteins (beta-catenin,
Cyclin D1 and octamer-binding transcription factor 4) in the spheres. In
conclusion, the present study demonstrated that SAL is an effective inhibitor of
canine mammary CSCs in vitro, indicating that SAL is a promising chemotherapeutic
agent for the treatment of canine mammary carcinoma.
PMID- 28693188
TI - Consecutive stimulation of HBsAg promotes the viability of the human B
lymphoblastoid cell line IM-9 through regulating the SIRT1-NF-kappaB pathway.
AB - Patients with chronic HBV infection have been reported to suffer a significantly
increased risk of NHL, but the underlying mechanisms remain to be clearly
explained. The aim of the present study was to clarify the relationship between
chronic HBV infection and NHL development. Fluorescence-activated cell sorting,
Annexin V/7-aminoactinomycin D staining and MTS assay were used to analyze the
rate of apoptosis and cell viability. In addition, western blotting was used to
detect protein expression. The effects of the activator of SIRT1, SRT1720, and
the inhibitor of SIRT1, nicotinamide, were also analyzed. The expression levels
cytokines and chemokines were determined by multiplex assay. Hepatitis B surface
antigen (HBsAg) was demonstrated to increase the viability of the human
peripheral B lymphoblastoid cell line, IM-9, in a dose- and time-dependent
manner. HBsAg also decreased histone H3 acetylation and p21 expression at the
molecular level. HBsAg upregulated the expression of anti-apoptotic B-cell
lymphoma-extra-large and B-cell lymphoma 2 proteins, and inactivated the
intrinsic apoptosis pathway by reducing BCL2 associated X, apoptosis regulator
expression and increasing the expression of sirtuin 1 (SIRT1) and nuclear factor
kappaB (NF-kappaB). HBsAg also altered the levels of certain chemokines and
cytokines, including interleukin (IL)-4, -10 and -12, C-X-C motif chemokine 10
and C-C motif chemokine ligand 5. Inhibition of SIRT1 suppressed the effects
induced by HBsAg. The anti-apoptotic effect of HBsAg in IM-9 cell lines occurred
via the promotion of cell viability, inhibition of apoptosis, regulation of
chemokines and cytokines, acetylation of histone H3 and alteration of SIRT1 and
NF-kappaB expression. In conclusion, chronic stimulation with HBsAg promoted the
viability of the human B lymphoblastoid cell line, IM-9, through regulation of
the SIRT1-NF-kappaB pathway. This may be an underlying mechanism of HBV
associated NHL.
PMID- 28693189
TI - Epigallocatechin gallate inhibits the growth of MDA-MB-231 breast cancer cells
via inactivation of the beta-catenin signaling pathway.
AB - Epigallocatechin gallate (EGCG), a major constituent of green tea, has potential
as a treatment for a variety of diseases, including cancer. EGCG induces
apoptosis and inhibits tumorigenesis through multiple signaling pathways in
breast cancer cells. beta-catenin signaling modulators could be useful in the
prevention and therapy of breast cancer. However, the precise anticancer effect
of EGCG through the beta-catenin signaling pathway in breast cancer is unclear.
The present study investigated the association between beta-catenin expression
and clinicopathological factors of breast cancer patients, and the effect of EGCG
on beta-catenin expression in breast cancer cells. beta-catenin expression was
analyzed according to the clinicopathological factors of 74 patients with breast
cancer. All patients were females diagnosed with invasive ductal carcinoma.
Western blot analysis revealed that beta-catenin was expressed at higher levels
in breast cancer tissue than in normal tissue. beta-catenin expression was
associated with lymph node metastasis (P=0.04), tumor-node-metastasis stage
(P=0.03) and estrogen receptor status (P<0.01). EGCG decreased MDA-MB-231 cell
viability and significantly downregulated the expression of beta-catenin,
phosphorylated Akt and cyclin D1. Remarkably, additive effects of LY294002 and
wortmannin, two phosphatidylinositol-3 kinase inhibitors, were observed. The
present results suggest that EGCG inhibits the growth of MDA-MB-231 cells through
the inactivation of the beta-catenin signaling pathway. Based on these promising
results, EGCG may be a potential treatment for triple negative breast cancer
patients.
PMID- 28693190
TI - Solamargine inhibits the migration and invasion of HepG2 cells by blocking
epithelial-to-mesenchymal transition.
AB - Solamargine (SM), a steroidal alkaloid glycoside purified from the Chinese
traditional herb Solanum incanum, is known to possess various biological
activities. However, only a few previous studies have reported the anti
metastatic activity of SM. In the present study, the inhibitory effects of SM on
metastatic action were investigated in human HepG2 cells. The proliferation
effects of SM on the HepG2 cells was evaluated by MTT and colony formation
assays. Wound-healing and Transwell assays were performed to examine the
migration and invasion effects on SM-treated HepG2 cells. The epithelial-to
mesenchymal transition (EMT)-associated markers (E-cadherin, Vimentin and N
cadherin) were detected by western blotting analysis. In the present study, MTT
and colony formation assays indicated that SM suppressed HepG2 cell viability in
a dose-dependent manner. The wound-healing and Transwell assays revealed that the
migration and invasion activities were significantly inhibited following exposure
to SM. EMT has been demonstrated to be essential for promoting migration and
invasion in tumor cells and has often been characterized with a loss of
epithelial markers (E-cadherin) and an increase of mesenchymal markers (Vimentin
and N-cadherin). In the western blotting analysis, the expression level of E
cadherin was significantly upregulated compared with that in the control group,
whereas the expression levels of N-cadherin and Vimentin were downregulated.
Thus, it was suggested that the underlying mechanism of SM inhibits migration and
invasion in HepG2 cells and is associated with suppression of EMT.
PMID- 28693191
TI - Effect of primary tumor location and tumor size on the response to radiotherapy
for liver metastases from colorectal cancer.
AB - Metastatic liver tumors (MLTs) from colorectal cancer (CRC) are often treated
with stereotactic body radiation therapy (SBRT). The present study aimed to
examine the predictive factors for response of MLTs to SBRT. A total of 39 MLTs
from 24 patients with CRC were retrospectively analyzed. Radiotherapy for MLT was
typically performed with a prescribed dose equivalent to a biologically effective
dose (BED)10 of 100 Gy. The median follow-up period was 16 months (range, 5-64
months). The median prescribed dose and total BED10 were 56 Gy (range, 45-72 Gy)
and 97.5 Gy (range, 71.7-115.5 Gy), respectively, in a median of 8 fractions
(range, 4-33 fractions). The 1- and 2-year local control rates were 67.2 and
35.9%, respectively. For patients with MLT treated with ablative SBRT (BED10
>=100 Gy in <=5 fractions), the 1- and 2-year local control rates were 83.3 and
62.5%, respectively. Univariate analysis showed that primary tumor location (left
sided colon), maximum tumor diameter (<=30 mm) and ablative SBRT (BED10 >=100 Gy
in <=5 fractions) were significantly associated with improved local control
(P=0.0058, P=0.0059 and P=0.0268, respectively). Multivariate analysis showed
that tumor diameter was significantly associated with improved local control
(P=0.0314). In addition, patients who received ablative SBRT had significantly
prolonged overall survival times compared with those treated with non-ablative
SBRT (P=0.0261). To conclude, tumors <=30 mm that can be treated with ablative
SBRT are associated with good local control rates. The primary tumor location may
affect the radiosensitivity of MLTs.
PMID- 28693192
TI - Regorafenib diminishes the expression and secretion of angiogenesis and
metastasis associated proteins and inhibits cell invasion via NF-kappaB
inactivation in SK-Hep1 cells.
AB - The aim of the present study was to investigate the effects of regorafenib on the
nuclear factor kappa-light-chain-enhancer of activated B cells (NF)-kappaB
modulated expression of angiogenesis- and metastasis-associated proteins and cell
invasion in human hepatocellular carcinoma SK-Hep1 cells. The SK-Hep1 cells were
treated with different concentrations of NF-kappaB inhibitor 4-N-[2-(4
phenoxyphenyl) ethyl] quinazoline-4,6-diamine (QNZ) or regorafenib for 24 or 48
h. The effects of QNZ and regorafenib on cell viability, NF-kappaB activation,
expression and secretion levels of angiogenesis- and metastasis-associated
proteins and cell invasion were evaluated with MTT assays, western blotting,
ELISA, gelatin zymography and cell invasion assays. The results demonstrated that
QNZ and regorafenib significantly reduced the expression and secretion levels of
the angiogenesis- and metastasis-associated proteins vascular endothelial growth
factor, tumor necrosis factor-alpha, interleukin (IL)-1beta, IL-6, matrix
metalloproteinase (MMP)-2 and MMP-9, NF-kappaB activation and cell invasion. In
conclusion, the inhibition of NF-kappaB activation induces anti-angiogenic and
antimetastatic effects in SK-Hep1 cells. Regorafenib reduces the level of
expression and secretion of angiogenesis- and metastasis-associated proteins and
cell invasion through the suppression of NF-kappaB activation in SK-Hep1 cells.
PMID- 28693193
TI - Allicin inhibits the invasion of lung adenocarcinoma cells by altering tissue
inhibitor of metalloproteinase/matrix metalloproteinase balance via reducing the
activity of phosphoinositide 3-kinase/AKT signaling.
AB - Allicin, the main active principle associated with Allium sativum chemistry, has
various antitumor activities. However, to the best of our knowledge, there is no
available information to address the anti-invasive effect and associated
mechanism in lung adenocarcinoma. In the present study, cell viability assay,
cell adhesion assay, western blot analysis, Transwell migration and invasion
assays and reverse transcription-quantitative polymerase chain reaction were
performed. Allicin was identified to inhibit the adhesion, invasion and migration
of lung adenocarcinoma cells in a dose-dependent manner, accompanied by
decreasing mRNA and protein levels of matrix metalloproteinase (MMP)-2 and MMP-9.
Conversely, the mRNA and protein levels of tissue inhibitor of metalloproteinase
(TIMP)-1 and TIMP-2 were increased in a dose-dependent manner. Furthermore, it
was revealed that allicin treatment significantly suppressed the phosphorylation
of AKT (P<0.05), but not the total protein expression of AKT. Combined treatment
with LY294002, an inhibitor of phosphoinositide 3-kinase (PI3K)/AKT signaling,
and allicin led to the synergistic reduction of MMP-2 and MMP-9 expression,
followed by an increase in TIMP-1 and TIMP-2 expression. The invasive
capabilities of lung adenocarcinoma cells were also suppressed. However, insulin
like growth factor-1 (an activator of PI3K/AKT signaling) reversed the effects of
allicin on cell invasion and expression of MMP-2, MMP-9, TIMP-1 and TIMP-2. The
present study concluded that allicin may inhibit invasion of lung adenocarcinoma
cells by altering TIMP/MMP balance, via reducing the activity of the PI3K/AKT
signaling pathway. This indicated that allicin may be recognized as an anti
invasive agent for lung adenocarcinoma treatment.
PMID- 28693194
TI - Combination of lenalidomide and low-dose dexamethasone therapy promotes the
anticoagulant activity of warfarin in patients with immunoglobulin light-chain
amyloidosis.
AB - The present study aimed to evaluate the drug interactions between warfarin and
combination chemotherapy with lenalidomide and low-dose dexamethasone in
immunoglobulin light-chain (AL) amyloidosis patients with unstable international
normalized ratios (INR). The changes to INR values over time in 3 AL amyloidosis
patients treated with warfarin and a combination of lenalidomide and low-dose
dexamethasone between March 2011 and February 2015 were analyzed retrospectively.
The mean INR value was 1.52 prior to the combination chemotherapy, and the value
increased 1.7-fold during treatment. The median time to reach maximum values was
17 days. Horn's drug Interaction Probability Scale indicated a possible
interaction between lenalidomide and warfarin. These patients exhibited no marked
alterations in hepatic function or serum albumin concentrations prior to and
following combination chemotherapy and no additional administration of CYP2C9
inhibitors or vitamin K supplements was conducted. In addition, no patient
experienced chemotherapy-induced nausea or appetite loss. These findings suggest
that the total clearance or protein binding of warfarin remained unchanged.
Therefore, the combination of warfarin and lenalidomide may cause a
pharmacodynamic interaction, more likely by inhibiting the production of
interleukin-6. In conclusion, clinically important interactions between warfarin
and lenalidomide and low-dose dexamethasone therapy were observed in AL
amyloidosis patients, where INR values signi ficantly increased. Therefore, close
and regular monitoring of patients during the course of treatment is important,
and the dose of warfarin should be reduced if required.
PMID- 28693195
TI - MicroRNA-125b targeted STAT3 to inhibit laryngeal squamous cell carcinoma cell
growth and motility.
AB - A majority of studies have indicated that microRNA-125b (miR-125b) is aberrantly
expressed in various types of cancer. However, there are no studies on the
expression and function of miR-125b in human laryngeal squamous cell carcinoma
(LSCC). In the present study, miR-125b expression in LSCC sample tissues,
corresponding adjacent non-neoplastic tissues, LSCC cell lines and a normal human
keratinocyte cell line was measured using the reverse transcription-quantitative
polymerase chain reaction. Following transfection with miR-125b mimics, the Cell
Counting Kit-8, cell migration, cell invasion, western blotting and dual
luciferase reporter assays were performed on LSCC cell lines. According to the
results, miR-125b was observed to be significantly downregulated in LSCC, and its
expression was significantly associated with clinical stage and alcohol history.
miR-125b was also observed to decrease cell growth, migration and invasion in
LSCC cells by directly targeting signal transducer and activator of transcription
3. The results of the present study suggested that miR-125b may be a potential
treatment target of LSCC in the future.
PMID- 28693196
TI - Early diagnosis of venous thromboembolism as a clinical primary symptom of occult
cancer: Core proteins of a venous thrombus.
AB - Malignancy is one of the risk factors of venous thromboembolism (VTE). As a
common accompanying factor of malignant tumors, almost 20% of idiopathic VTEs are
identified in patients with occult types of cancer as the primary symptom. The
type of internal association that exists between malignant tumors and VTE has not
yet been determined. The present review discusses the following: i) Reversible
combinations between core proteins of venous thrombi and their ligand proteins.
With the condition of immune cell balancing function collapse, which is
characterized as dysfunction immune cells and impaired immune functions, the
human body loses the function of eliminating infectious/malignant cells quickly
and effectively. Thus, integrins beta2 and beta3 on the membrane of platelets and
white blood cells are activated to combine with fibrinogen ligands to form an
intravenous mesh-like structure, which acts as an intravenous biological filter
that prevents infectious/malignant cells from flowing back into the circulatory
system. During the defense process, blood cells (mainly red blood cells) stagnate
and fill the filter, which results in venous thrombotic diseases. ii) Tumor
cells, which cannot be eliminated quickly, proliferate and invade; or ischemic
necrosis destroys peripheral tissues and vessels (veins and arteries), resulting
in the formation of a biological filter in injured veins. The filter is filled
with stranded tumor cells, which prevents the hemorrhagic metastasis of malignant
cells. The formation of an intravenous biological filter results from the
transition of the body's own defense capabilities, which is also a
physical/histopathological phenomenon. iii) An increase in the number of core
proteins in a venous thrombus is a basic molecular step in the formation of
intravenous biological filters, which is also defined as a marker of the newly
initiated defensive barrier. Increased levels of integrins beta1, beta2 and beta3
are useful in not only the specific diagnosis of VTE, but also in the early
recognition of occult malignant tumors in idiopathic VTE patients.
PMID- 28693197
TI - Recent developments in predictive biomarkers of pediatric glioma.
AB - The presence of certain cancer-related genetic and epigenetic alterations in the
tumor affects patient response to specific cancer therapies. The accurate
screening of these predictive biomarkers in molecular diagnostics is important
since it enables the tailoring of optimal treatment based on molecular
characteristics of the tumor. We searched the electronic database PubMed for
preclinical as well as clinical controlled trials reporting on various multiple
predictors of glioma. It was observed clearly that multiple approaches are
evolving and a few of them have also shown promising results. Depending on the
type of gene alteration, a wide variety of methods may be applied in biomarker
testing. Among the novel methods is next-generation sequencing (NGS) technology,
enabling simultaneous detection of multiple alterations. The aim of this review
is to discuss the predictive or potentially predictive genetic and epigenetic
alterations of diffuse gliomas. The review concludes that NGS technology is the
future and may likely replace, at least to some extent, the current routinely
used methods, including FISH, IHC, and PCR-based methods, in clinical
diagnostics.
PMID- 28693198
TI - Pulmonary toxicity generated from radiotherapeutic treatment of thoracic
malignancies.
AB - Radiation-induced lung injury (RILI) remains a major obstacle for thoracic
radiotherapy for the treatment of lung cancer, esophageal cancer and lymphoma. It
is the principal dose-limiting complication, and can markedly impair the
therapeutic ratio as well as a patient's quality of life. The current review
presents the relevant concepts associated with RILI, including the pathogenic
mechanisms and the potential treatment strategies, so as to achieve a general
understanding of this issue. RILI comprises an acute radiation pneumonitis phase
and subsequent late lung fibrosis. The established assessment criteria are
clinical manifestations, imaging changes and the necessity for medical
assistance. Risk factors are also considered in order to optimize treatment
planning. Due to the underlying molecular mechanisms of RILI, the present review
also discusses several targeted pharmacological approaches for its treatment, as
well as corticosteroid therapy.
PMID- 28693199
TI - Epidermal growth factor receptor in glioblastoma.
AB - Mutations in the epidermal growth factor receptor (EGFR) are commonly occurring
in glioblastoma. Enhanced activation of EGFR can occur through a variety of
different mechanisms, both ligand-dependent and ligand-independent. Numerous
evidence has suggested that EGFR is overexpressed in most of primary
glioblastomas and some of the secondary glioblastomas and is characteristic of
more aggressive glioblastoma phenotypes. Additionally, recent studies have
revealed that wild-type EGFR, and to a greater extent hyper-activating EGFR
mutants induced a substantial upregulation of Fyn expression. Furthermore, it was
determined that Fyn expression is upregulated across a panel of patient-derived
glioblastoma stem cells (GSCs) relative to normal progenitor controls. Moreover,
researchers are continuously involved in elucidation of novel mechanism linking
EGFR EGFR-expressing glioblastoma. The present review highlights current aspects
of EGFR receptor in glioblastoma and concludes that the concept of EGFR signaling
and related receptors and associated factors is evolving, however, it needs
detailed evaluation for future clinical applications in cancer patients.
PMID- 28693200
TI - Sorafenib induced alteration of protein glycosylation in hepatocellular carcinoma
cells.
AB - Sorafenib is a multikinase inhibitor and is effective in treating hepatocellular
carcinoma (HCC). However, it remains unknown whether sorafenib induces the
alteration of protein glycosylation. The present study treated HCC MHCC97L and
MHCC97H cells with a 50% inhibitory concentration of sorafenib. Following this
treatment, alteration of protein glycosylation was detected using a lectin
microarray. Compared with the controls, the binding capacity of glycoproteins
extracted from sorafenib-treated HCC cells to the lectins Bauhinia purpurea
lectin, Dolichos biflorus agglutinin, Euonymus europaeus lectin, Helix aspersa
lectin, Helix pomatia lectin, Jacalin, Maclura pomifera lectin and Vicia villosa
lectin were enhanced; while, the binding capacities to the lectins Caragana
arborescens lectin, Lycopersicon esculentum lectin, Limulus polyphemus lectin,
Maackia amurensis lecin I, Phaseolus vulgaris leucoagglutinin, Ricinus communis
agglutinin 60, Sambucus nigra lectin and Solanum tuberosum lectin were reduced
(spot intensity median/background intensity median >=2, P<0.05). This difference
in glycoprotein binding capacity indicates that cells treated with sorafenib
could increase alpha-1,3GalNAc/Gal, beta-1,3 Gal, GalNAcalpha-Ser/Thr(Tn) and
alpha-GalNAc structures and decrease GlcNAc, sialic acid, tetra-antennary complex
type N-glycan and beta-1,4Gal structures. These results were additionally
confirmed by lectin blotting. Expression levels of signaling molecules including
erythroblastosis 26-1 (Ets-1), extracellular signal-related kinases (ERK) and
phosphorylated-ERK were measured by western blotting. There was a reduction in
the expression of Ets-1 and ERK phosphorylation in sorafenib or 1,4-Diamino-2,3
dicyano-1,4-bis (2-aminophenylthio) butadiene treated cells suggesting that
sorafenib may reduce the expression levels of Ets-1 by blocking the
Ras/Raf/mitogen activated protein kinase signaling pathway. In the present study,
it was clear that sorafenib could inhibit the proliferation of HCC cells and
alter protein glycosylation. The findings of this study may lead to providing a
novel way of designing new anti-HCC drugs.
PMID- 28693201
TI - S100P is associated with proliferation and migration in nasopharyngeal carcinoma.
AB - In the present study, the function of S100 calcium binding protein P (S100P) in
the C666-1 nasopharyngeal carcinoma (NPC) cell line was examined. The levels of
S100P protein in NPC tissues were analyzed using immunohistochemistry, and small
interfering RNA silenced S100P expression in C666-1 cells. Subsequently, cell
proliferation, colony formation, migration and wound-healing assays were
performed in order to assess whether the knockdown of S100P was able to influence
the biological behavior of C666-1 cells. The expression levels of the receptor
for advanced glycation end products (RAGE) were analyzed using a western blot
following the inhibition of S100P. The immunohistochemistry results revealed that
S100P was elevated in expression in 45/78 (57.7%) of patients with NPC, as
compared with 5/30 (16.7%) of patients with benign inflammation. The S100P
protein levels correlated with the rates of proliferation and migration in C666-1
cells. Additionally, reduced S100P expression levels altered a series of
intracellular events, including the downregulation of epidermal growth factor
receptor, cluster of differentiation (CD) 44, matrix metalloproteinase (MMP) 2
and MMP9 protein expression. In addition, RAGE expression was downregulated in
the S100P silenced C666-1 cells, as detected by western blot analysis. These data
suggest that S100P is important during the development and progression of
nasopharyngeal cancer. Therefore, S100P may provide a novel treatment target for
NPC.
PMID- 28693202
TI - pPeOp from Omphalia lapidescens Schroet induces cell cycle arrest and inhibits
the migration of MC-4 gastric tumor cells.
AB - The aim of the present study was to investigate the effect of purified Omphalia
lapidescens protein (pPeOp) extracted by polyvinylpyrrolidone from the fungus
Omphalia lapidescens Schroet on the proliferation and cell cycle progression of
MC-4 human gastric tumor cells. Using polyvinylpyrrolidone, pPeOp was extracted
from O. lapidescens Schroet. MC-4 cells were cultured with 30, 60 or 90 ug/ml
pPeOp, with 5-fluorouracil used as a positive control. Survival rates of treated
cells were significantly decreased compared with those of the untreated control
group in a dose-dependent manner. Using flow cytometric analysis, cells treated
with pPeOp were demonstrated to arrest in S phase and exhibit abnormal G0/G1 and
G2/M phase cell cycle distribution. In addition, a wound healing assay
demonstrated that pPeOp significantly inhibited the migration of MC-4 cells. The
mRNA and protein expression levels of cyclin D1/cyclin-dependent kinase (CDK) 4,
cyclin B/CDK1, cyclin A/CDK2, matrix metalloproteinase (MMP)-2 and MMP-9 were
determined using reverse transcription-quantitative polymerase chain reaction
analysis and western blotting. The mRNA expression level of CDK4 and cyclin A was
significantly increased compared with the untreated control; however, cyclin D1,
CDK1, CDK2, cyclin B, MMP-2, and MMP-9 exhibited a significantly decreased mRNA
expression level, indicating that there is a negative association between
concentration and cyclin D1 expression levels. The expression of the cycle arrest
associated proteins and migration-associated proteins examined were similar to
the observed mRNA expression levels. In conclusion, pPeOp was identified to
inhibit migration of and cause S phase cell cycle arrest in MC-4 cells.
PMID- 28693203
TI - Involvement of the TGFbeta1/Smad2/MMP3 signaling pathway in SB431542-induced
inhibition of cell invasion in multiple myeloma RPMI 8226 cells.
AB - Multiple myeloma (MM) is a malignancy characterized by plasma cell hyperplasia.
The majority of patients with MM suffer from mortality due to tumor recurrence
and metastasis, which has become an emerging clinical problem. Transforming
growth factor beta1 (TGFbeta1) has been implicated in tumor metastasis; however,
its role in RPMI 8226 cells remains to be elucidated. In the present study, RPMI
8226 cells were treated with various concentrations of SB431542, a TGFbeta1
inhibitor, for 12, 24 and 48 h. RPMI 8226 cells were transfected with lentiviral
TGFbeta1 vectors to overexpress TGFbeta1. Cell proliferation rate was
subsequently determined by cell-counting kit-8 assay and cell invasion was
assessed by Transwell assay. Expression of TGFbeta1, SMAD family member 2 (Smad2)
and matrix metallopeptidase 3 (MMP3) were analyzed by western blotting. The
results demonstrated that cell proliferation and invasion of RPMI 8226 cells was
significantly inhibited by SB431542 (P<0.05). SB431542 was able to significantly
downregulate the expression of TGFbeta1, phosphorylated (p)-Smad2 and MMP3;
however, the overexpression of TGFbeta1 significantly upregulated the expression
of TGFbeta1, p-Smad2 and MMP3. In conclusion, SB431542 reduced cell invasion in
RPMI 8226 cells, and this effect may be mediated via the TGFbeta1/Smad2/MMP3
signaling pathway.
PMID- 28693204
TI - Treatment of a mixed acinar-endocrine carcinoma with uptake on 68Gallium-DOTATOC
positron emission tomography-computed tomography: A case report.
AB - The case of a 35-year old female patient with a diagnosis of metastatic mixed
acinar-endocrine carcinoma (MAEC) is investigated in the present study. The
patient was believed to have a well-differentiated neuroendocrine tumor (NET)
with a high Ki-67 index and uptake on 68Gallium-DOTATOC positron emission
tomography-computed tomography for 9 years, and was treated accordingly. The
patient had long lasting disease control by treatment with sunitinib, and a
response was observed in numerous lesions with peptide receptor radionuclide
therapy (PRRT). Following treatment for metastatic disease for >4 years, liver
transplantation was performed, as an exception to normal recommendations, at the
time of progression of a centrally located liver lesion inducing obstructive
jaundice. Following transplantation, the diagnosis of a Grade 3 NET, as defined
by the WHO 2010 classification, was challenged and changed to MAEC. MAEC is a
rare type of tumor of the pancreas, exhibiting endocrine and acinar
differentiation. It is difficult to diagnose, often being misidentified as acinar
cell carcinoma or predominantly as neuroendocrine neoplasms. Immunohistochemical
labelling provides the only evidence for the dual differentiation of
neuroendocrine (synaptophysin and chromogranin) and acinar (lipase, trypsin and
chymotrypsin) cell markers. Studies investigating MAECs with a clear
histopathological diagnosis are scarce, in addition to evidence of disease
behaviour and treatment options. It is generally agreed that surgery is the
primary treatment in patients with resectable tumors. The responses to sunitinib
and PRRT suggested that treatments considered or developed for NETs may be
beneficial in MAEC cases.
PMID- 28693205
TI - Oncogenic function of angiopoietin-2 in vitro and its modulation of tumor
progression in colorectal carcinoma.
AB - Angiopoietin-2 (Ang-2) has been investigated in cancer primarily in terms of its
angiogenic function, and its role as an oncogene has yet to be elucidated. The
current study hypothesized that Ang-2 may be an oncogene and have a function in
tumor progression. An investigation of the function of Ang-2 in the LoVo
colorectal cancer (CRC) cell line in vitro, which expresses a high level of Ang
2, was performed by knocking down endogenous expression with a targeted short
hairpin RNA. The aggressive phenotypic effects of Ang-2 on experimental and
control group cells were assessed using cell proliferation, migration and
invasion assays. The association between Ang-2 expression levels and
clinicopathological factors was evaluated in 415 CRC tissues using
immunohistochemistry. Suppressing Ang-2 expression decreased cellular
proliferation, invasion and migration in an in vitro study. Ang-2 overexpression
was observed in 46% of patients with CRC and was significantly associated with pT
(P=0.048), pN (P<0.001), venous invasion (P=0.023), lymphatic invasion (P<0.001)
and tumor-node-metastasis stage (P=0.022). Furthermore, Ang-2 overexpression was
an independent prognostic factor in pN stages 1 and 2. These results reveal that
Ang-2 may be an oncogene in colorectal carcinogenesis and its expression may
exert aggressive phenotypic effects during tumor progression. In addition, Ang-2
expression may serve as a prognostic marker and a potential drug target.
PMID- 28693206
TI - Role of T helper 17 cytokines in the tumour immune inflammation response of
patients with laryngeal squamous cell carcinoma.
AB - Altered cytokine production can lead to immune dysfunction in patients with
cancer. The present study investigated the expression of T helper (Th)17
cytokines in patients with laryngeal squamous cell carcinoma (LSCC) and their
clinical significance in providing new therapeutic insights. The prevalence of
Th17 cells and their receptors in patients with LSCC was studied using
immunohistochemical analysis via tissue microarray technology. Flow cytometry was
used to investigate the percentage of Th17 and Th1 cells in peripheral blood
mononuclear cells. Furthermore, the proliferation of Th17 cells and Th17
associated cytokines, including interleukin (IL)17, IL23 and RAR-related orphan
receptor gammat, was analyzed by reverse transcription-quantitative polymerase
chain reaction. The results revealed that the prevalence of Th17 cells in
patients with LSCC was elevated in their primary tumors, as well as in peripheral
blood, compared with that in healthy controls. It was further demonstrated that
Th17 cells could be induced and expanded in the tumor microenvironment through
cytokines produced by the tumor cells. In conclusion, Th17 cells have a
substantial impact on the carcinogenesis of LSCCs, and could serve as a potential
therapeutic target to modulate the anti-tumor response in these carcinomas.
PMID- 28693207
TI - 99mTc-LHRH in tumor receptor imaging.
AB - Detection of gonadotropin-releasing hormone (GnRH) also known as luteinizing
hormone-releasing hormone (LHRH) in the relevant tumor tissue and normal tissues
and organs in vivo expression was investigated. To examine the method of direct
radio labeling of LHRH by 99mTc with relatively high radiochemical purity and
stability, screening the best labeling conditions, to establish a simple and
reliable method of preparation of 99mTc-LHRH was undertaken. The detection of
radioisotope-labeled LHRH distribution in mice, LHRH receptor imaging for the
study and treatment of cancer basis were evaluated. i) Immunohistochemical
staining test was used in 23 patients with hepatocellular carcinoma (HCC), 20
patients with breast cancer, 10 patients with prostate cancer, 20 patients with
lung cancer, 20 patients with endometrial cancer tumor cells and normal tissue
LHRH-R De Biaoda levels; ii) pre-tin method use direct labeling of LHRH, marking
completion of saline or human serum were added at room temperature, the
chromatography was measured at different times, to calculate the rate of labeled
product and the radiochemical purity of the label, in vivo observation of its
stability, and comparative analysis of selected optimal condition; iii) rat
pituitary cell membrane protein, the product of in vitro radio-receptor marker
analysis, through the saturation and inhibition experiments, was used to test its
receptor binding activity; iv) Ch-T method labeled 125I-LHRH, tail vein injection
of normal mice at different times were sacrificed, blood and major organs were
determined and calculated per gram organization percentage injected dose rate (%,
ID/g). Detected by immunohistochemistry in 23 cases of HCC in the LHRH-positive
rate was 82.61%, in the corresponding normal tissues, the positive rate was 15%;
20 cases of breast cancer positive rate of 95%, the corresponding normal tissues,
the positive rate was 20%; 10 cases of prostate cancer positive rate of 70%, the
corresponding normal tissues, the positive rate of 40%; 20 cases of lung cancer
positive rate of 85%, the corresponding normal tissues, the positive rate of
15.79%; 20 cases of endometrial cancer positive rate of 80% in the corresponding
normal tissues was 16.67% positive. 99mTc-LHRH mark was 97.9-100.0%, the
radiochemical purity of 93.9-96.4%, marking the reaction gel content of <5%.
Great product receptor marker analysis showed 99mTc-LHRH with saturable receptor
binding characteristics and inhibition, and high affinity, RT = 23.2174 pmol, KD
= 0.4348 nmol; intravenous injection of 131I-LHRH within 72 h after the mice
rapidly cleared the blood radioactivity, the major radioactive accumulation in
the liver and kidneys and by the liver, renal clearance, and other tissues and
organs of the radioactivity gradually decreased with time. In conclusion, i) the
liver, lung, breast, prostate, endometrial cancer exist in both LHRHR; ii) 99mTc
LHRH preparation is simple, rapid, radiochemical purity product obtained higher
marks, better stability, no further purification; and iii) LHRH 99mTc labeled,
still has a high receptor binding ability, biological activity; and has an ideal
and realistic dynamics in animals, there is hope, as with the clinical value of
imaging agent of GnRH receptors.
PMID- 28693208
TI - Efficacy and safety of SOX chemotherapy with or without surgery in AFP-producing
advanced gastric cancer.
AB - The present study investigated the clinical efficacy of S-1 plus oxaliplatin
(SOX) regimen, with or without surgery in alpha-fetoprotein-producing gastric
cancer (APGC) with liver metastasis. A total of 24 patients with APGC treated at
the Liaocheng People's Hospital between January 2011 and December 2013 were
retrospectively reviewed. Clinical efficacy and patient safety were compared
between the two groups. The median progression-free survival (PFS) and overall
survival (OS) in the SOX group were 6.5 [95% confidence interval (CI), 4.6-8.4]
and 13.5 (95% CI, 8.1-18.9) months, respectively. The corresponding indicators in
the SOX and surgery group were 7.0 (95% CI, 5.7-8.3) and 14 (95% CI, 11.0-17.1)
months, respectively. There was no significant difference in PFS and OS between
the two groups (P=0.703 and 0.710, respectively). The adverse effects of
leucopenia, neutropenia, anemia and diarrhea occurred in ~10% of patients in the
SOX group and in 14.3% (2/14), 7.14% (1/14), 14.3% (2/14) and 7.14% (1/14),
respectively, in the surgery group. No significant difference was identified
between groups in terms of overall incidence of adverse effects (P=0.17).
However, severe adverse events, including gastroplegia, pancreatic fistula,
pulmonary infection and refractory ascites, occurred only in the SOX plus surgery
group [incidence rate for severe adverse events, 7.14% (1/14); P<0.001 between
groups]. In conclusion, SOX chemotherapy is safe and effective in patients with
APGC and liver metastasis. However, the addition of surgery to SOX chemotherapy
may not improve the disease control rate and may increase the adverse effects.
PMID- 28693209
TI - Frequent aberrant p53 and Fhit expression in endoscopically resected superficial
hypopharyngeal cancer and esophageal cancer.
AB - In the last decade, the incidence rate of detection rate of superficial head,
neck and esophageal squamous cell carcinomas has increased with the development
of endoscopic imaging techniques. These cancers are thought to arise
independently subsequent to tissue exposure to a common carcinogen e.g. alcohol
or tobacco. This phenomenon has been termed field cancerization. To determine the
molecular background of the development of hypopharyngeal squamous cell
carcinomas (HPSCCs) and double esophageal squamous cell carcinomas (DESCCs), the
present study immunohistochemically assessed tumor-related protein expression
[p53, Fhit (fragile histidine triad), E-cadherin and activation-induced cytidine
deaminase (AID)], and subsequently determined the correlation between protein
expression and clinicopathological data. Tumor specimens of 9 HPSCCs and 9 DESCCs
were endoscopically obtained from 8 patients with HPSCC. The 9 DESCCs, including
5 synchronous and 4 metachronous lesions, were all obtained from four patients
with HPSCC. The overexpression of p53 and loss of Fhit expression was
immunohistochemically detected in 8 (88.9%) and 8 (88.9%) of the 9 HPSCCs and in
8 (88.9%) and 8 (88.9%) of the 9 DESCCs, respectively, which demonstrated the
high frequency of such expression. Additionally, 7 out of 9 HPSCCs, and 7 out of
9 DESCCs demonstrated aberrant expression of p53 and Fhit. The rate of aberrant
AID and E-cadherin expression was 67 and 44% in HPSCCs and 44 and 44% in DESCC,
respectively. These results suggested that aberrant p53 and Fhit expression was
involved in the development of HPSCC and their DESCC, and that their expression
may be used for the prediction of DESCC development in patients with HPSCC,
thereby acting as a biomarker of field cancerization.
PMID- 28693210
TI - Resistance to epithelial growth factor receptor tyrosine kinase inhibitors in a
patient with transformation from lung adenocarcinoma to small cell lung cancer: A
case report.
AB - First-generation epithelial growth factor receptor tyrosine kinase inhibitors
(EGFR-TKIs) have markedly improved the treatment of non-small cell lung cancer
(non-SCLC) with EGFR-sensitive mutations. However, acquired resistance to these
drugs was inevitable. The transformation of lung adenocarcinoma to SCLC following
treatment with EGFR-TKIs is a rare phenomenon that contributes to resistance to
EGFR-TKIs. The present case concerns a 74-year-old man previously diagnosed with
and treated for pneumonia; however, this was later pathologically confirmed as
lung adenocarcinoma by transbronchial lung biopsy. Deletion of exon 19 of EGFR
was identified by next-generation sequencing technology. The patient improved
markedly when treated with gefitinib, but relapsed after 1 year, with markedly
increased serum levels of neuron-specific enolase (NSE). Transformation to SCLC
was detected by endobronchial ultrasound transbronchial needle aspiration (EBUS
TBNA) re-biopsy, which was negative for the deletion of exon 19 of EGFR. The
patient was positive for vimentin expression and refractory to etoposide and
cisplatin chemotherapy, and succumbed to the disease 18 months after diagnosis.
Transformation of the disease from adenocarcinoma to SCLC may have been due to
cancer heterogeneity. Re-biopsy is therefore important in EGFR-TKI-resistant
patients for genetic and histological re-evaluation. NSE serum levels may also be
useful for detecting early SCLC transformation.
PMID- 28693211
TI - Predictive role of human equilibrative nucleoside transporter 1 in patients with
pancreatic cancer treated by curative resection and gemcitabine-only adjuvant
chemotherapy.
AB - The predictive roles of human equilibrative nucleoside transporter 1 (hENT-1) in
patients who undergo curative resection and adjuvant chemotherapy with
gemcitabine alone have not been established. The present study retrospectively
analyzed the clinical data from 101 consecutive patients who underwent curative
resection and who received gemcitabine adjuvant chemotherapy for the treatment of
pancreatic cancer at Kanagawa Cancer Center (Yokohama, Japan) between 2005 and
2014. The associations between the hENT-1 status and the survival and
clinicopathological features of the patients were investigated. Of the 101
patients, 60 patients (59.4%) had high levels of hENT-1 expression. A significant
association was observed between hENT-1 status and sex; however, for all the
other clinicopathological parameters, including tumor and node stages, no
differences were observed between the high and low hENT-1 expression groups. The
median follow-up period of the present study was 67.3 months. Between the high
and low hENT-1 expression groups, there was a statistically significant
difference in the 5-year overall survival (OS) rates following surgery (20.6 and
8.9%, respectively; P=0.019). In addition, a significant difference was observed
in the recurrence-free survival (RFS) rates at 5 years following surgery
(P=0.049). hENT-1 status was one of the important predictive factors for OS and
RFS in patients with pancreatic cancer who underwent curative resection followed
by adjuvant chemotherapy with gemcitabine. Adjuvant chemotherapy with gemcitabine
alone may be insufficient, particularly in patients with certain relevant risk
factors.
PMID- 28693212
TI - Korean Scutellaria baicalensis Georgi flavonoid extract induces mitochondrially
mediated apoptosis in human gastric cancer AGS cells.
AB - Korean Scutellaria baicalensis Georgi has been widely used in Korean folk
medicines for its range of medicinal benefits, including its anticancer effect.
The aim of the present study was to investigate the underlying molecular
mechanism of action of a flavonoid extract from Korean Scutellaria baicalensis
Georgi (FSB) on AGS human gastric cancer cells (gastric adenocarcinoma) in which
FSB exhibits an anticancer effect. Treatment of AGS cells with FSB significantly
inhibited cell viability in a concentration-dependent manner. Furthermore, FSB
significantly increased the proportion of cells in sub-G1 phase, and Annexin V
and Hoechst 33258 fluorescent staining confirmed the apoptotic cell death.
Furthermore, western blotting results identified that treatment of AGS cells with
FSB significantly downregulated the expression of caspase family members, namely
procaspases 3 and 9, and poly(ADP-ribose) polymerase (PARP), and subsequently
upregulated cleaved caspase 3 and cleaved PARP. It was observed that FSB
treatment significantly decreased the mitochondrial membrane potential of AGS
cells. In addition, the ratio of the mitochondrion-associated proteins B cell
lymphoma 2-associated X protein and B cell lymphoma extra large was upregulated.
The results of the present study provide novel insight into the underlying
molecular mechanism of the anticancer effects of FSB on AGS human gastric cancer
cells and indicate that FSB may be an alternative chemotherapeutic agent for the
treatment of gastric cancer.
PMID- 28693213
TI - Recruitment of CD11b+Ly6C+ monocytes in non-small cell lung cancer xenografts
challenged by anti-VEGF antibody.
AB - A series of antibodies against vascular endothelial growth factor (VEGF) have
been developed for the treatment of various types of cancer, including non-small
cell lung cancer (NSCLC) in recent years. However, tumors frequently demonstrate
resistance to these strategies of VEGF inhibition. Efforts to better understand
the mechanism underlying the acquired resistance to anti-VEGF antibodies are
warranted. In the present study, in order to develop a xenograft model of
acquired resistance to anti-VEGF antibody, xenografts of human adenocarcinoma
A549 cells were generated through the successive inoculation of tumor tissue
explants into first (F1), second (F2) and third (F3) generations of mice treated
with the anti-VEGF antibody B20. Tumor growth rate and vessel-forming ability,
assessed via cluster of differentiation (CD) 31 staining, were significantly
lower in the F1, F2 and F3 groups compared with in the F0 control group (P<0.01),
suggesting that drug resistance was not successfully acquired. The percentages of
CD11b+ myeloid-derived suppressor cells and lymphocyte antigen 6C (Ly6C)+ subsets
were significantly smaller in F1, F2 and F3 groups compared with in F0 (P<0.01).
However, the ratio of Ly6C+ to CD11b+ cells was significantly higher in the F3
group compared with in F0 and F1 groups (P<0.01), indicating increasing
recruitment of the Ly6C+ subset with successive challenges with the anti-VEGF
antibody. In conclusion, the recruitment of CD11b+Ly6C+ monocytes increased with
successive generations of NSCLC-xenografted mice challenged by B20, an anti-VEGF
agent.
PMID- 28693214
TI - Clustering of patients with intrahepatic cholangiocarcinoma based on serum
periostin may be predictive of prognosis.
AB - An effective serum biomarker may improve cholangiocarcinoma (CCA) management.
Periostin (PN) has been demonstrated to be associated with aggressive CCA. The
current study evaluated PN in blood serum for its diagnostic and prognostic
potential in patients with CCA. Sera of 68 patients with CCA were collected prior
to treatment, and PN levels were measured using an ELISA. Sera from 50 normal
controls, 6 patients with benign liver diseases, 2 with hepatocellular carcinoma
and 21 with breast cancer were analyzed. Immunohistochemistry of PN in CCA
tissues was also investigated. The data were analyzed using the Mann-Whitney U
test, Kaplan-Meier log rank tests, Cox proportional hazard regression models and
Fisher's exact tests. The median serum PN level in patients with CCA was
significantly increased compared with that in healthy controls, patients with
benign liver diseases and patients with breast cancer (all P<0.05). Using an
optimal threshold value of 94 ng/ml PN, the diagnostic values for CCA compared
with other conditions demonstrated a sensitivity level of 0.38 [95% confidence
interval (CI), 0.27-0.51], specificity of 0.90 (95% CI, 0.81-0.96), accuracy of
0.66 (95% CI, 0.58-0.74), positive predictive value of 0.76 (95% CI, 0.59-0.89)
and negative predictive value of 0.63 (95% CI, 0.53-0.72) (P<0.001). Furthermore,
PN stain in stromal fibroblasts in CCA tissues was associated with serum PN
levels (P=0.001), and patients with CCA were classified as low (<=94 ng/ml) or
high PN (>94 ng/ml) accordingly. High serum and tissue PN levels were
significantly associated with reduced survival rate (P<0.001 and P=0.033,
respectively). Serum PN was an independent prognostic factor with a hazard ratio
of 3.197 (P=0.001). In conclusion, serum PN may be used to divide patients with
intrahepatic CCA into high and low PN groups. Elevated serum PN may be utilized
as a marker of poor prognosis in patients with CCA.
PMID- 28693215
TI - Expression of FOXC2, PinX1, Ki-67 and Cyclin D1 in cutaneous cell carcinoma.
AB - We investigated the expression of FOXC2, PinX1, Ki-67 and Cyclin D1 in cutaneous
cell carcinoma. We collected 30 cutaneous squamous cell carcinoma (SCC), 30
cutaneous basal cell carcinoma (BCC) and 30 normal skin tissues. The protein
expression and gene expression of FOXC2, endogenous telomerase-inhibiting gene
PinX1, Ki-67 and Cyclin D1 was measured by immunohistochemistry (IHC) and semi
quantitative reverse transcription polymerase chain reaction (RT-PCR),
respectively. In SCC and BCC tissues, the positive rate of protein expression and
mRNA level of PinX1 were both significantly lower than those in normal tissues.
However, the positive rate of protein expression and mRNA level of FOXC2, Ki-67
and Cyclin D1 were significantly higher than those in normal tissues (p<0.05).
There was no significant difference between SCC and BCC (p>0.05). In conclusion,
FOXC2 may participate in the carcinogenesis process of SCC and BCC. It may also
correlate with the expression PinX, Ki-67 and Cyclin D1. However, FOXC2 alone
cannot be used as a diagnostic indicator of SCC.
PMID- 28693216
TI - Trifluridine/tipiracil increases survival rates in peritoneal dissemination mouse
models of human colorectal and gastric cancer.
AB - A number of patients exhibit peritoneal dissemination of gastric or colorectal
cancer, which is a predominant cause of cancer-associated mortality. Currently,
there is no markedly effective treatment available. The present study was
designed to determine the efficacy of trifluridine/tipiracil (TFTD), formerly
known as TAS-102, which is used for the treatment of patients with unresectable
advanced or recurrent colorectal cancer refractory to standard therapies. Four
colorectal cancer cell lines and one gastric cancer cell line were
intraperitoneally inoculated into nude mice, as models of peritoneal
dissemination. TFTD (200 mg/kg/day) was orally administered for 5 consecutive
days followed by 2 drug-free days for 6 weeks. The increase in the lifespan (ILS)
of the TFTD-treated mice compared with that of the drug-free control mice was
66.7, 43.3, 106.3, 98.3 and 133.3% for DLD-1, DLD-1/5-fluorouracil [5
fluorouracil (5FU)-resistant subline of DLD-1], HT-29 and HCT116 colorectal
cancer cell lines, and MKN45 gastric cancer cell line, respectively. This ILS was
similar to that of the irinotecan-treated mice (ILS, 70-84%), but was
significantly (P<0.05) increased compared with that of the 5FU-, tegafur,
gimeracil and potassium oxonate- and cisplatin-treated mice (ILS, 1-53%, 0.8-60%
and 85%, respectively). No significant increase in body weight loss was observed
during the dosing periods with any of the drugs used. The increase in CEA levels
with progressive peritoneal dissemination was inhibited by TFTD treatment. TFTD
also exhibited marked anticancer effects against Kirsten rat sarcoma viral
oncogene homolog-mutated tumors and 5FU-resistant tumors. The results of the
present study indicate that TFTD may be a potential drug against peritoneal
dissemination of colorectal and/or gastric cancer in humans and may be utilized
for chemo-naive tumors and recurrent tumors following 5FU treatment.
PMID- 28693217
TI - Transforming growth factor-beta1 contributes to oxaliplatin resistance in
colorectal cancer via epithelial to mesenchymal transition.
AB - Transforming growth factor-beta1 (TGF-beta1), secreted by main components of
tumor microenvironment, is considered to be closely associated with cancer
development and chemoresistance. The present study aimed to analyze the effects
and mechanisms underlying TGF-beta1-induced chemoresistance to oxaliplatin (LOH)
in human colorectal cancer (CRC) cell lines. The cytotoxic effects of LOH
subsequent to TGF-beta1 treatment were assessed in three CRC cell lines by MTT
assay. In addition, epithelial to mesenchymal transition (EMT), DNA damage and
apoptosis assays were performed to evaluate the mechanisms of drug resistance in
vitro. It was revealed that an exposure of CRC cells to TGF-beta1 induced EMT.
This was followed by a decrease in the levels of DNA damage and LOH-induced
apoptotic cell death at certain TGF-beta1 concentrations compared with untreated
cells, which was responsible for LOH resistance. TGF-beta1 leads to resistance to
LOH in CRC cells, primarily through EMT. These data not only provide insight into
the understanding of the chemoresistant mechanisms, but also may guide the
clinical applications of reducing EMT to enhance the sensitivity to chemotherapy,
by targeting TGF-beta1.
PMID- 28693218
TI - Meta-analysis of the role of bevacizumab in extensive stage small cell lung
cancer.
AB - Progress in the treatment options for small cell lung cancer (SCLC) remains poor.
Concerns exist regarding the efficacy of bevacizumab in SCLC. The present study
aimed to evaluate the efficacy of bevacizumab in extensive stage (ES)-SCLC. A
meta-analysis on studies conducted and listed on the Medline, Cochrane Trials,
ASCO, ESMO and ClinicalTrial databases, and Chinese databases prior to April 2015
was performed. All clinical trials in which patients with ES-SCLC were treated
with bevacizumab were considered. Survival rates at specific time points were
extracted from the reported survival curves. Hazard ratios (HR) for progression
free survival (PFS) and overall survival (OS), rates for PFS, OS, overall
response rate (ORR), and side-effects were synthesized using random-effects or
fixed-effects model. Two randomized control trials (RCT) (176 patients) and six
single-arm trials (292 patients) were identified. In RCTs, no statistically
significant differences were observed in PFS [HR, 0.70; 95% confidence interval
(CI), 0.41-1.19; P=0.19] or OS (HR, 1.21; 95% CI, 0.84-1.75; P=0.31). In the
first-line trials, pooled 6-month and 1-year PFS rates were 57% (95% CI, 39-76%)
and 10% (95% CI, 4-16%), respectively. Synthesized 1-year and 2-year OS rates
were 45% (95% CI, 36-54%) and 10% (95% CI, 6-14%), respectively. Reported median
PFS and OS times for pretreated patients were 2.7-4.0 months and 6.3-7.4 months,
respectively. Pooled ORRs were 71% (95% CI, 59-82%) in the first-line trials and
18% (95% CI, 11-25%) in the second-line trials. The most common types of reported
toxicities were chemotherapy-associated, including neutropenia, leukopenia,
fatigue and thrombocytopenia. According to the RCTs, bevacizumab did not appear
to improve the PFS or OS for patients with ES-SCLC, with low quality of evidence.
Due to the disappointing pooled efficacy in the single-arm trials, more clinical
studies on bevacizumab in SCLC may not be valuable, although the evidence was
with low quality.
PMID- 28693219
TI - F-18 fluorodeoxyglucose positron emission tomography for differential diagnosis
and prognosis prediction of vascular tumors.
AB - The spectrum of vascular tumors ranges from hemangioma (HEM), to epithelioid
hemangioendothelioma (EHE) and to angiosarcoma (AS). To the best of our
knowledge, the usefulness of F-18 fluorodeoxyglucose positron emission tomography
(FDG-PET) for vascular tumors has never been comprehensively studied. The present
study investigated the usefulness of FDG-PET for pathologically diagnosed
vascular tumors. The present study included 26 patients with vascular tumor
(male:female, 17:9; age, 60.9+/-14.4 years; 7 HEM, 6 EHE and 13 AS) who underwent
FDG-PET between January 2007 and May 2014 at the Seoul National University
Bundang Hospital (Seongnam, Korea) and Konkuk University Medical Center, (Seoul,
Korea). Representative FDG uptake was measured as the maximum standardized uptake
value (SUVmax) over the lesion with the highest FDG uptake. Disease progression
was clinically defined as the aggravation of known lesions or novel lesion
development during follow-up on computed tomography, magnetic resonance imaging,
or FDG-PET. FDG-PET revealed multi-organ involvement only in AS (6/13 [46.2%]),
whereas HEM and EHE involved a single organ. Tumor SUVmax was significantly
greater in AS (6.32+/-4.84) compared with EHE (3.10+/-2.68) and HEM (2.33+/-0.76)
(P=0.0284). There was no difference in tumor SUVmax between HEM and EHE (P>0.05).
Disease progression was primarily noticed in AS (9/13 [69.2%]). Only 1 patient
with EHE (1/6=16.7%) and no patients with HEM (0/7=0%) experienced disease
progression. Mortality was reported only in patients with AS (4/13 [30.8%]).
Using the cutoff SUVmax of 3.0, the two-year progression-free survival rate of 14
patients with tumor SUVmax <3.0 (75.0%) was significantly higher compared with
that of 12 patients with tumor SUVmax >=3.0 (0%) (P=0.0053). In conclusion, FDG
PET is useful for the differential diagnosis and prognosis prediction of vascular
tumors.
PMID- 28693220
TI - Remodeling of energy metabolism by a ketone body and medium-chain fatty acid
suppressed the proliferation of CT26 mouse colon cancer cells.
AB - Normal and cancerous cells are suggested to have differential utilization of
fatty acids and ketone bodies, which could be exploited in cancer therapy. The
present study examined the effect of 3-hydroxybutyric acid (3-HBA), which is a
ketone body generating acetyl-CoA, and lauric acid (LAA, C12:0), which is a
medium-chain saturated fatty acid translocated to mitochondria in a carnitine
independent manner to produce acetyl-CoA, on the energy metabolism of mouse CT26
colon cancer cells. In CT26 cells expressing 3-HBA and LAA transporters, 3-HBA
and LAA reduced cell proliferation, mitochondrial volume and lactate production,
and increased oxidative stress, particularly in low-glucose conditions.
Concurrent treatment with 3-HBA and LAA under glucose starvation had a
synergistic effect on cell growth inhibition. In addition, LAA and LAA + 3-HBA
promoted an imbalance in the expression of enzymes in the electron transport
chain. These findings suggested that treatment with 3-HBA and/or LAA during
glucose starvation may reprogram energy metabolism and decrease the proliferation
of cancer cells.
PMID- 28693221
TI - Fatty acids inhibit anticancer effects of 5-fluorouracil in mouse cancer cell
lines.
AB - The present study investigated the effects of two major dietary fatty acid
components, linoleic acid (LA) and elaidic acid (EA), on the antitumor effects of
5-fluorouracil (5-FU) in the LL2, CT26 and CMT93 mouse cancer cell lines.
Concurrent treatment with LA and 5-FU elicited a decreased cell viability
compared with treatment with 5-FU alone. In addition, increased inhibition of
growth was observed following concurrent treatment with EA and 5-FU. Sequential
treatment of LA followed by 5-FU abrogated the anticancer effects of 5-FU, and
treatment with EA followed by 5-FU increased cancer cell growth in addition to
abrogating the anticancer effects of 5-FU. The expression of the stem cell
markers CD133 and nucleostemin (NS) increased in all three cell lines treated
concurrently with 5-FU and either LA or EA when compared with cells treated with
5-FU alone. Aldehyde dehydrogenase activity in the cancer stem cells (CSCs), in
response to concurrent treatment with 5-FU and either LA or EA, was increased
compared with 5-FU treatment alone. 5-FU inhibited the growth of CT26 tumors, but
co-treatment with either LA or EA abrogated this effect. NS-positive CSCs were
more abundant in CT26 tumors treated with 5-FU and either LA or EA compared with
those treated with 5-FU alone. The results of the present study suggested that,
rather than altering the sensitivity of cancer cells to 5-FU, LA and EA may
promote the survival of CSCs. The results indicated that dietary composition
during chemotherapy is an important issue.
PMID- 28693222
TI - Identification of differentially expressed inflammatory factors in Wilms tumors
and their association with patient outcomes.
AB - The present study aimed to identify differentially expressed inflammatory factors
observed in Wilms tumors (WT), and to investigate the association of these
factors with clinical stage, pathological type, lymph node metastasis and
vascular involvement of WT. Surface-enhanced laser desorption/ionization-time of
flight mass spectrometry was performed to screen differentially expressed
proteins among WT and normal tissue pairs. Upregulated proteins in WT were
separated and purified by solid phase extraction and Tricine SDS-PAGE,
respectively. Following in-gel digestion, the peptide mixture was subjected to
liquid chromatography mass spectrometry to identify proteins on the basis of
their amino acid sequences. Immunohistochemistry was used to confirm the
expression of differentially expressed inflammatory proteins. Of the proteins
that were upregulated in WT, two proteins with mass/charge (m/z) ratio of 12,138
and 13,462 were identified as macrophage migration inhibitory factor (MIF) and C
X-C motif ligand 7 (CXCL7) chemokine, respectively. The expression of these two
proteins was increased in WT compared with adjacent normal tissues and normal
renal tissues, and increased with increasing clinical stage. In addition, their
expression was significantly increased in patients with unfavorable pathological
type, lymph node metastasis and vascular involvement compared with the groups
with favorable type, and without lymph node metastasis or vascular involvement
(P<0.05). Increased pro-inflammatory MIF and CXCL7 expression in WT is closely
associated with the clinical stage, pathological type, lymph node metastasis and
vascular involvement, and may represent biomarkers for the clinical diagnosis of
WT.
PMID- 28693223
TI - Distinct subcellular localization of E-cadherin between epithelioid
angiomyolipoma and triphasic angiomyolipoma: A preliminary case-control study.
AB - Epithelioid angiomyolipoma (EAML) is a rare variant of angiomyolipoma (AML).
Previous studies have demonstrated that epithelial (E-)cadherin is expressed in
two subtypes of AML, EAML and triphasic AML; however, the expression pattern of E
cadherin remains unclear. In the present study, a preliminary case-control study
was conducted to determine the expression pattern of E-cadherin between EAML and
triphasic AML, the control, focusing on the subcellular localization and
expression category of E-cadherin. No significant difference was identified in
the age, sex, history of tuberous sclerosis, smoking and alcohol consumption
between the two groups (P>0.05). In EAML, 9 patients were categorized as
exhibiting a low risk of malignant behavior and the other two were categorized as
exhibiting an intermediate or high risk of malignant behavior. The proportion of
cases expressing E-cadherin, human melanoma black-45 (HMB45), melanoma antigen
recognized by T cells 1 (Mart1/Melan A), smooth muscle actin and progesterone
receptor were 95.5 (21/22), 95.5 (21/22), 86.4 (19/22), 77.3 (17/22) and 86.4%
(19/22), respectively. E-cadherin was identified to be localized, using staining
techniques, in the cell membrane and/or cytoplasm. The subcellular localization
of E-cadherin was significantly different between EAML and triphasic AML; the
majority of EAML cases revealed membranous and cytoplasmic staining, whereas
triphasic AML cases demonstrated cytoplasmic staining (P=0.0093). The expression
of E-cadherin may be positively associated with HMB45 (P=0.0044) and Mart1/Melan
A (P=0.0049). The results of the present study identified that the subcellular
localization of E-cadherin may be different between EAML and the control group of
triphasic AML. Additionally, E-cadherin and melanocytic markers may be co
expressed in distinct subtypes of AML. A follow-up study with a large sample size
to validate the results of the present study, followed by a mechanistic study
based on cell lines to determine any significance, are warranted.
PMID- 28693224
TI - Validation and ranking of seven staging systems of hepatocellular carcinoma.
AB - The aim of the present study was to evaluate the ability of seven staging systems
to predict 3- and 6-month and cumulative survival rates of patients with advanced
hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC). Data were
collected from 220 patients with HBV-associated HCC who did not receive any
standard anticancer treatment. Participants were patients at The Third Affiliated
Hospital of Sun Yat-sen University from September 2008 to June 2010. The
participants were classified according to the Chinese University Prognostic Index
(CUPI), the Cancer of the Liver Italian Program (CLIP), Japan Integrated Staging
(JIS), China Integrated Score (CIS) systems, Barcelona Clinic Liver Cancer
(BCLC), Okuda and tumor-node-metastasis (TNM) staging systems at the time of
diagnosis and during patient follow-up. The sensitivity and specificity of the
predictive value of each staging system for 3- and 6-month mortality were
analyzed by relative operating characteristic (ROC) curve analysis with a non
parametric test being used to compare the area under curve (AUC) of the ROC
curves. In addition, log-rank tests and Kaplan-Meier estimator survival curves
were applied to compare the overall survival rates of the patients with HCC
defined as advanced using the various staging systems, and the Akaike information
criterion (AIC) and likelihood ratio tests (LRTs) were used to evaluate the
predictive value for overall survival in patients with advanced HCC. Using
univariate and multivariate Cox's model analyses, the factors predictive of
survival were also identified. A total of 220 patients with HBV-associated HCC
were analyzed. Independent prognostic factors identified by multivariate analyses
included tumor size, alpha-fetoprotein levels, blood urea nitrogen levels, the
presence or absence of portal vein thrombus, Child-Pugh score and neutrophil
count. When predicting 3-month survival, the AUCs of CLIP, CIS, CUPI, Okuda, TNM,
JIS and BCLC were 0.806, 0.772, 0.751, 0.731, 0.643, 0.754 and 0.622,
respectively. When predicting 6-month survival, the AUCs of CLIP, CIS, CUPI,
Okuda, TNM, JIS and BCLC were 0.828, 0.729, 0.717, 0.692, 0.664, 0.746 and 0.575,
respectively. For 3-month mortality, the prognostic value of CLIP ranked highest,
followed by CIS; for 6-month mortality, the prognostic value of CLIP also ranked
highest, followed by JIS. No significant difference between the AUCs of CLIP and
CIS (P>0.05) in their predictive value for 3-month mortality was observed. The
AUC of CLIP was significantly higher compared with that of the other staging
systems (P<0.05) for predicting 6-month mortality. The chi2 values from the LRTs
of CLIP, CIS, CUPI, Okuda, TNM, JIS and BCLC were 75.6, 48.4, 46.7, 36.0, 21.0,
46.8 and 7.24, respectively. The AIC values of CLIP, CIS, CUPI, Okuda, TNM, JIS
and BCLC were 1601.5, 1632.3, 1629.9, 1641.1, 1654.8, 1627.4 and 1671.1,
respectively. CLIP exhibited the highest chi2 value and lowest AIC value,
indicating that CLIP has the highest predictive value of cumulative survival
rate. In the selected patients of the present study, CLIP was the staging system
best able to predict 3- and 6-month and overall survival rates. CIS ranked second
in predicting 3-month mortality.
PMID- 28693225
TI - Dynamic MRI follow-up of radiation encephalopathy in the temporal lobe following
nasopharyngeal carcinoma radiotherapy.
AB - The natural course of radiation encephalopathy following nasopharyngeal carcinoma
(NPC) radiotherapy remains poorly understood. The present study aimed to
investigate the magnetic resonance imaging (MRI) characteristics and evolution of
radiation encephalopathy. A series of 162 follow-up MRI examinations from 68 NPC
patients with radiation encephalopathy in the temporal lobes were analyzed
retrospectively. Each component of radiation encephalopathy was defined as
follows: i) contrast enhanced lesions were enhanced lesions on contrast enhanced
T1-weighted images (T1WI); ii) white matter lesions were lesions of homogeneous
hyperintensity on T2-weighted images (T2WI) and hypointensity on T1WI; iii) cysts
were round or oval well-defined lesions of hyperintensity on T2WI; iv)
hemosiderin deposition were nodular or annular hypointense lesions with lower
hypointense than normal white matter on both T1WI and T2WI; v) gray matter
lesions were defined as disruption or erosion of hyperintensity in the cortex on
T2WI. Contrast enhanced lesions, white matter lesions, gray matter lesions, cysts
and hemosiderin deposition were detected in 105 (100.0%), 98 (93.3%), 94 (89.5%),
2 (1.7%) and 2 (1.7%) cases of the 105 initial diagnosed temporal lobe lesions.
Contrast enhanced lesions were the most commonly observed, followed by white
matter lesions, gray matter lesions, temporal lobe atrophy, cysts and hemosiderin
deposition. In addition, 12 new lesions were identified during the follow-up, 4
of which presented as solid enhanced nodular lesions. Importantly, in 11 of the
117 (9.4%) affected temporal lobes, solid enhanced nodular lesions were observed
to be the only initial abnormalities to occur. For those enhanced nodular lesions
measuring <0.8 cm, no necrosis could be detected. On the contrary, all the
contrast enhanced lesions measuring >2.0 cm exhibited a necrotic core. To the
best of our knowledge, the present study revealed for the first time solid
enhanced nodular lesions as the earliest MRI abnormalities of radiation
encephalopathy following NPC radiotherapy.
PMID- 28693226
TI - Screening of potentially crucial genes and regulatory factors involved in
epithelial ovarian cancer using microarray analysis.
AB - The present study aimed to screen potential genes implicated in epithelial
ovarian cancer (EOC) and to further understand the molecular pathogenesis of EOC.
In order to do this, datasets GSE14407 (containing 12 human ovarian cancer
epithelia samples and 12 normal epithelia samples) and GSE29220 (containing 11
salivary transcriptomes from ovarian cancer patients with serous papillary
adenocarcinoma and 11 matched controls) were obtained from the Gene Expression
Omnibus. Differentially expressed genes (DEGs) within these datasets were
screened using the Linear Models for Microarray Data package, and potential gene
functions were predicted by functional and pathway enrichment analyses.
Additionally, module analysis of protein-protein interaction networks was
performed using MCODE software in Cytoscape. The potential microRNAs
(miRNAs/miRs) and transcription factors (TFs) regulating DEGs were also analyzed,
and the integrated TF-DEG and miRNA-DEG regulatory networks were visualized with
Cytoscape. In total, 31 upregulated DEGs and 64 downregulated DEGs were screened.
The upregulated DEGs, such as centromere protein F (CENPF) and ubiquitin like
with PHD and ring finger domains 1 (UHRF1), were significantly associated with
the cell cycle and were regulated by the TF nuclear transcription factor Y (NF
Y). CENPF was modulated by miR-373, and UHRF1 was regulated by miR-146a. The
downregulated DEGs, such as aldehyde dehydrogenase 1 family member A2 (ALDH1A2),
were distinctly involved in the response to estrogen stimulus and modulated by
tumor protein 53 (TP53); protocadherin 9 (PCDH9) was regulated by TP53, miR-92b
3p and miR-137. The DEGs, including CENPF, UHRF1, ALDH1A2 and PCDH9, and a set of
gene regulators, including all NFY genes, TP53, miR-373, miR-146a, miR-92b-3p and
miR-137, may be involved in the pathogenesis of EOC.
PMID- 28693227
TI - Polymorphisms of -800G/A and +915G/C in TGF-beta1 gene and lung cancer
susceptibility.
AB - We studied the relationship between the polymorphisms of -800G/A and +915G/C in
transforming growth factor-beta1 (TGF-beta1) gene and lung cancer susceptibility.
The sequence-specific primer polymerase chain reaction (PCR-SSP) technique was
used to test 156 non-small cell lung cancer (NSCLC) patients that were selected
as the observation group and 156 patients with pneumonia and tuberculosis that
were selected as the control group (age and gender 1:1 proximal matching
principle) and the polymorphisms of the first exon -800G/A and +915G/C TGF-beta1
genes. The expression of TGF-beta1 levels in peripheral blood was detected using
ELISA. The proportion of -800G/A gene AA subtype and A allelic gene in the
observation group was significantly higher than that in the control group, while
the proportion of +915G/C gene CC subtype and C allelic gene was also
significantly higher than that in the control group (P<0.05). The cancer risk
[odds ratio (OR)] of patients with A allelic gene in -800G/A gene was 4.8 (95%
CI=2.563-6.537, P<0.05), while the cancer risk (OR) of patients with C allelic
gene in +915G/C gene was 4.7 (95% CI=2.317-5.864, P<0.05). The serum TGF-beta1
expression levels of -800G/A gene AA subtype in the observation group was
significantly higher than the GG type, GA type and the control group, while the
TGF-beta1 level of +915G/C gene CC subtype was significantly higher than the GG
type, GC type and the control group (P<0.05). Therefore, the polymorphisms of
800G/A and +915G/C in TGF-beta1 gene are closely related to the lung cancer
susceptibility.
PMID- 28693228
TI - Expression of methylation-modulated tumor-related genes in endoscopically
resected early esophageal squamous neoplasia.
AB - Smoking and alcohol consumption are major risk factors for the development of
esophageal squamous cell carcinoma (ESCC). Recent studies have demonstrated that
smoking and alcohol consumption may be associated with altered DNA methylation in
human cancer development. The aim of the present study was to evaluate
methylation-modulated protein expression of tumor-related genes (TRGs) in the
early stages of esophageal squamous neoplasia (ESN). ESN tissue samples (n=141)
comprising 19 cases of low-grade intraepithelial neoplasia (LGIN), 70 of high
grade intraepithelial neoplasia/carcinoma in situ (HGIN/CIS) and 52 of invasive
cancer, were endoscopically resected. The methylation-modulated protein
expression of 5 TRGs [fragile histidine triad (FHIT), E-cadherin, MutL homolog 1
(MLH1) /MutS homolog 2 (MSH2) and cyclooxygenase-2 (COX-2)] as well as p53 was
examined with immunohistochemistry, and their expression was compared with
patient clinicopathological characteristics. Reduced or loss of FHIT, E-cadherin,
MLH1/MSH2 and COX-2 expression was detected in 26.3 (5/19), 5.3 (1/19), 0 (0/19)
and 63.2% (12/19) of LGIN cases, 61.4 (43/70), 18.6 (13/70), 7.1 (5/70) and 65.7%
(46/70) of HGIN/CIS cases, and 78.8 (41/52), 50.0 (26/52), 11.5 (6/52) and 59.6%
(31/52) of invasive cancer cases, respectively. Reduced or absent expression of
FHIT and E-cadherin was significantly associated with neoplastic progression
(FHIT, P=0.0007; E-cadherin, P=0.00014). The mean number of TRGs (FHIT, E
cadherin, MLH1/MSH2, and COX-2) that exhibited reduced or absent expression in
LGIN, HGIN/CIS and invasive cancer specimens was 1.12+/-0.61, 1.66+/-0.93 and
2.09+/-0.96, respectively, demonstrating a significant stepwise increment from
LGIN to HGIN/CIS and then to invasive cancer (P<0.05). p53 overexpression was
frequently detected in ESN with head and neck carcinomas. However p53
overexpression was not significantly associated with ESN progression. An increase
in the number of the 5 TRG proteins with reduced or loss of expression in the
early stages of esophageal tumorigenesis was demonstrated, and their decreased
expression was observed to be associated with tumor progression. Therefore,
smoking and alcohol drinking may be associated with not only carcinogenesis but
also the progression of ESN.
PMID- 28693229
TI - MicroRNAs as outcome predictors in patients with metastatic colorectal cancer
treated with bevacizumab in combination with FOLFOX.
AB - Bevacizumab is a humanized anti-vascular endothelial growth factor monoclonal
antibody, used in combination with a oxaliplatin-based chemotherapy in the
treatment of metastatic colorectal cancer (mCRC). The aim of the present study
was to identify microRNA (miRNA)-based predictive biomarkers of therapy response
in order to avoid unnecessary and costly therapy to non-responding patients. High
throughput miRNA microarray profiling (Affymetrix miRNA array) was performed on a
discovery cohort of patients with mCRC. The discovery cohort was (n=20) divided
into either responding (n=10) or non-responding (n=10) groups of bevacizumab/5
flourouracil, leucovorin, oxaliplatin (FOLFOX) treatment according to Response
Evaluation Criteria in Solid Tumors criteria. Validation of candidate miRNAs was
performed on an independent cohort of 41 patients with mCRC using quantitative
reverse transcription polymerase chain reaction. Normalized data were subjected
to receiver operating characteristic and Kaplan-Meier analyses. In total, 67
miRNAs were identified to be differentially expressed when miRNA expression was
compared between responding and non-responding patients to bevacizumab/FOLFOX
treatment (P<0.05). A total of 7 miRNAs were chosen for independent validation,
which confirmed significantly higher expression of miR-92b-3p, miR-3156-5p, miR
10a-5p and miR-125a-5p (P<0.005) in tumor tissue of responding patients compared
with non-reponding patients. Using the combination of miRNAs, the present study
identified responders to the therapy with sensitivity 82% and specificity 64%
(area under the curve = 0.8015). In conclusion, 4 predictive miRNAs associated
with progression-free survival (PFS) were identified in patients with mCRC
treated with bevacizumab/FOLFOX. Following further independent validations,
detection of these miRNA may enable identification of patients with mCRC who may
potentially benefit from the therapy.
PMID- 28693230
TI - Apogossypolone induces apoptosis and autophagy in nasopharyngeal carcinoma cells
in an in vitro and in vivo study.
AB - Nasopharyngeal carcinoma (NPC) has a high incidence and mortality rate,
particularly in Southern China. Apogossypolone (ApoG2) is a novel derivative of
gossypol with antitumor activity and less toxicity. The human NPC CNE-2 cell line
was studied in the in vitro model; whilst 4 week-old male nude mice (BALB/c-nu)
were inoculated subcutaneously with CNE-2 cells, and xenograft tumors were
studied in the in vivo model. Graded concentrations of ApoG2 were used in
treatment studies. In ApoG2-treated and control in vitro and in vivo tumor cells,
cell apoptosis, and autophagy were evaluated and quantified using fluorescent and
transmission electron microscopy and flow cytometry. Hoechst-33258 fluorescence
staining was used to evaluate apoptosis in treated and non-treated cell culture
and xenograft NPC cells. Western blotting was performed on lysed tumor cells
using primary antibodies to B-cell lymphoma-2 (Bcl-2), beclin-1, and beta-actin,
and flow cytometry results indicated cell apoptosis rates of 3.90+/-0.34 and
19.52+/-1.18% in the control and ApoG2-treated cells, respectively (F=485.294,
P<0.001). Western blot analysis showed that ApoG2 significantly decreased
expression of the Bcl-2 protein in CNE-2 cells, when compared with control cells
(F=68.909, P=0.001) and flow cytometry showed cell autophagy rates of 0.92+/
3.10% of control cells compared with 28.24+/-7.35% of ApoG2-treated cells
(F=31.035, P=0.003). ApoG2 treatment significantly increased beclin-1 protein
expression in CNE-2 cells (F=497.906, P<0.001). ApoG2 treatment inhibited NPC
xenograft tumor growth by 65.49% (P<0.05). In conclusion, these results support a
role for ApoG2 in inhibiting the growth of human NPC cells by inducing apoptosis
and autophagy. Future controlled clinical studies could be planned, to define
safety, efficacy and dosing regimens for ApoG2 as a potential treatment for
patients with NPC.
PMID- 28693231
TI - Impact of RASSF1A gene methylation on the metastatic axillary nodal status in
breast cancer patients.
AB - Hypermethylation of CpG islands is a hallmark of cancer and occurs at an early
stage in breast tumorigenesis. To gain insight into the epigenetic switches that
may promote and/or contribute to the initial neoplastic events during breast
carcinogenesis, the present study focused on the DNA methylation profile of
invasive breast carcinoma. The aim of the study was to evaluate the prognostic
significance of Ras association domain family 1 isoform A (RASSF1A) promoter
methylation status in operable breast cancer, and to analyze the utility of this
biomarker regarding its association with metastatic and nonmetastatic axillary
nodal status. For this purpose, formalin-fixed, paraffin-embedded tissue
specimens from 116 breast cancer patients with known axillary nodal status were
subjected to assessment of RASSF1A promoter methylation status by methylation
specific polymerase chain reaction (MSP) and methylation-sensitive high
resolution melting assay, and the results were subsequently validated by
bisulfite sequencing. A multinomial logistic regression model was used to model
the dependence of distinct levels of methylation status of the RASSF1A promoter
on the nodal status. Promoter region CpG hypermethylation was identified by MSP
in 97 (83.6%) of 116 primary breast tumors, while hypermethylation of RASSF1A was
confirmed by MS-HRM in 107 (92.2%) of 116 cases of breast cancer. Based on the
results of the multinomial logistic regression model, there was no significant
difference between the frequency of RASSF1A promoter methylation and axillary
lymph node status of patients in general. However, upon adjustment of pN stage,
an association was identified between pN0 lymph node-negative status (without
axillary metastases) and percentage of RASSF1A methylation in two groups of
heterogeneous methylated alleles with <=50% methylated (P<0.05) and >50%
methylated alleles (P<0.0001). If a patients' nodal status changes from pN- to
pN+ then the risk of having >50% methylated alleles increases by 7%. The present
study revealed a specific phenomenon, suggesting that the presence of
heterogeneous methylated alleles in the RASSF1A gene is significantly associated
with lymph node-negative status in breast cancer patients. Furthermore, greater
significance with negative axillary nodal status was observed with a higher level
of heterogeneous methylated alleles in the RASSF1A gene.
PMID- 28693232
TI - MicroRNA-195 inhibits the behavior of cervical cancer tumors by directly
targeting HDGF.
AB - MicroRNAs (miRNAs/miRs) are a class of conserved non-coding endogenous small
regulatory RNAs that regulate target gene expression by binding to the 3'
untranslated region of target mRNAs in a base-pairing manner, resulting in
repression of transcription or degradation of target mRNAs. It has been
demonstrated previously that the abnormal expression of miRNAs is involved in the
carcinogenesis and progression of cervical cancer. The aim of the present study
was to investigate the expression, biological functions and underlying molecular
mechanisms of miR-195 in cervical cancer. The reverse transcription-quantitative
polymerase chain reaction (RT-qPCR) was used to detect the expression level of
miR-195 in cervical cancer tissues and cell lines. Following transfection, an MTT
assay, cell migration and invasion assays, western blot analysis and a dual
luciferase reporter assay were performed in human cervical cancer cells. In the
present study, it was identified that miR-195 was downregulated in cervical
cancer tissues and cell lines. Additionally, upregulation of miR-195 and
knockdown of hepatoma-derived growth factor (HDGF) inhibited proliferation,
migration and invasion of cervical cancer cells. Furthermore, a dual-luciferase
reporter assay identified that HDGF was a direct target gene of miR-195. RT-qPCR
and western blot analysis demonstrated that miR-195 mimic inhibited HDGF
expression at the mRNA and protein levels, whereas miR-195 inhibitor enhanced
HDGF expression at the mRNA and protein levels. These results indicated that miR
195 targeted HDGF to inhibit the behavior of tumors in cervical cancer. These
results also suggested that miR-195 was a potential therapeutic biomarker of
cervical cancer.
PMID- 28693233
TI - Pre-operative evaluation of circulating KL-6 levels as a biomarker for epithelial
ovarian carcinoma and its correlation with tumor MUC1 expression.
AB - Krebs von den Lungen-6 (KL-6), a mucinous sialylated sugar chain on human mucin-1
glycoprotein (MUC1), is a diagnostic marker for interstitial lung diseases.
Furthermore, elevated serum KL-6 levels have been observed in certain malignant
tumor types of epithelial origin. The expression of MUC1 has been observed in
patients with epithelial ovarian cancer (EOC) and is considered a potential
therapeutic target. In the present study, KL-6 serum levels were investigated in
patients clinically suspected of having malignant ovarian tumors. A total of 219
patients were enrolled in the study, which analyzed their serum KL-6 levels in
addition to tumor expression of MUC1 using immunohistochemistry. High serum KL-6
levels were predominantly observed in patients with EOC, and did not occur in
patients with benign or borderline tumors. The level of serum KL-6 was highly
correlated with tumor stage, grade and histological type, and demonstrated
superior sensitivity for the detection of ovarian cancer compared with that of
serum cancer antigen 125. High serum KL-6 was significantly associated with
shorter progression-free survival. In addition, tumor MUC1 expression status was
significantly correlated with serum KL-6 levels. These data suggest that serum KL
6 may be a useful, non-invasive biomarker surrogate for tumor MUC1 expression in
future clinical trials of MUC1-targeted therapy.
PMID- 28693234
TI - Relapsed anaplastic lymphoma kinase-positive large B-cell lymphoma expressed
cluster of differentiation 4 and cytokeratin: An initially misdiagnosed case
corrected by immunoglobulin kappa locus gene rearrangement detection.
AB - Anaplastic lymphoma kinase (ALK)-positive large B-cell lymphoma (LBCL) is a rare
lymphoma subtype. The present study investigated a refractory nodal ALK-positive
LBCL case in a 28-year-old Chinese male. It was initially misdiagnosed as ALK
positive anaplastic large cell lymphoma; however, the patient's lesions relapsed
and spread widely following a short remission for chemotherapy and the patient
succumbed to the disease 3 months' post-autologous stem cell transplantation;
thus, a revision was performed. Histologically, the tumor cells exhibited a
characteristic immunoblastic morphology with marked cellular pleomorphism. All
lesions shared the same immunoprofiles, including granular cytoplasmic ALK
staining patterns and a lack of cell lineage-associated markers, with the
exception of cluster of differentiation (CD)45 and CD4. CD30 expression was
revealed to be negative and CD138 staining was observed to be positive,
additionally, cytokeratin was expressed aberrantly in a relapsed tumor biopsy.
Fluorescence in situ hybridization studies demonstrated breakage and extra copies
of the ALK gene in >=30% of cells. Final clarification was provided by the
detection of immunoglobulin kappa locus (IGK) gene rearrangement in clonality
studies [but notimmunoglobulin heavy locus (IGH) and immunoglobulin lambda locus
(IGL) genes]. This aggressive entity requires distinct modalities of standard
treatment, and may be ignored owing to its rarity in routine pathology
laboratories. BIOMED-2 polymerase chain reaction assays, including for IGH, IGK
and IGL genes, are essential for the detection of gene rearrangement.
PMID- 28693235
TI - Japanese apricot extract (MK615) potentiates bendamustine-induced apoptosis via
impairment of the DNA damage response in lymphoma cells.
AB - Bendamustine, a hybrid molecule of a purine analog and alkylator, induces cell
death by the activation of apoptosis and the DNA damage response. The agent MK615
is produced from Japanese apricot and contains a number of cyclic triterpenes
that exhibit antitumor activities. In the present study, the combined effects of
bendamustine and MK615 on lymphoma cells were investigated. The combined
compounds synergistically induced apoptosis in all lymphoid cell lines examined.
MK615 inhibited the bendamustine-induced phosphorylation of checkpoint kinase 1
and 2. As ataxia telangiectasia mutated (ATM) and ataxia telangiectasia- and Rad3
related (ATR) kinases are key mediators of the DNA damage response, the effects
of the combination of bendamustine and ATM/ATR inhibitors (KU-60019 and VE-821)
on lymphoma cells were investigated. KU-60019 and/or VE-821 potentiated
bendamustine activity in all cell lines tested, but did not affect MK615
activity, suggesting that these inhibitors have the same underlying mechanism of
action as that of MK615. The results of the present study suggest that it may be
feasible to use ATM/ATR inhibitors in combination with bendamustine for treating
malignant lymphoma.
PMID- 28693236
TI - Significance of CD47 expression in gastric cancer.
AB - Integrin-associated protein (CD47) is ubiquitously expressed on the surface of
cells and functions as an identifier of self. In blood cancer, tumor cells
expressing CD47 evade phagocytosis by macrophages, leading to a poor patient
prognosis. However, the status of CD47 expression in solid tumors, particularly
in gastric cancer, is not well understood. The purpose of the present study was
to examine the level of CD47 in the primary tumor, peripheral blood (PB) and bone
marrow (BM) of patients with gastric cancer, and to determine its effect. Reverse
transcription-quantitative polymerase chain reaction analysis was performed to
determine the level of CD47 mRNA expression in primary tumor, PB and BM samples
collected from 168 patients with gastric cancer. Cell sorting was performed to
investigate CD47 protein expression in PB and BM fractions, and to identify the
source of CD47 expression. In primary tumors, the expression of CD47 was not
associated with any clinicopathological factors or prognosis. By contrast, in PB,
the low CD47 expression group demonstrated a significantly increased tumor size,
and frequency of lymphatic invasion and lymph node metastasis, compared with the
high CD47 expression group. In addition, the clinical tumor stage of the low CD47
expression group was significantly increased compared with that of the high CD47
expression group. Conversely, in PB, the high CD47 expression group had a
significantly higher frequency of lymphatic invasion and lymph node metastasis
compared with the low CD47 expression group. The lymphocyte fraction exhibited
the highest CD47 expression compared with the other fractions in PB and BM
samples. Low expression of CD47 was associated with the advancement of gastric
cancer, in contrast to other cancers, and it may be associated with a decrease in
lymphocytes during later stages. These results indicate that CD47 expression in
the PB and BM may serve as a marker to analyze the immunological function of
patients with gastric cancer; however, the significance of CD47 in gastric cancer
requires further study.
PMID- 28693237
TI - Inhibitory effects of delphinidin on the proliferation of ovarian cancer cells
via PI3K/AKT and ERK 1/2 MAPK signal transduction.
AB - Delphinidin is a member of the anthocyanidin family and is a natural pigment in
red cabbage, berries, sweet potatoes and grapes. It possesses nutraceutical
properties against various chronic diseases and types of cancer. However, little
is known about its preventative effects on epithelial ovarian cancer, a disease
that is associated with a low survival rate, a poor prognosis and a high rate of
recurrence. The results of the present study demonstrated that the proliferation
of SKOV3 cells decreased in a dose-dependent manner in response to treatment with
delphinidin, and the phosphorylation of carcinogenic protein kinases associated
with the progression of epithelial ovarian cancer was affected by delphinidin
treatment. The levels of phosphorylated protein kinase B (AKT), ribosomal protein
S6 kinase beta-1 (P70S6K), ribosomal protein S (S6), extracellular signal
regulated kinase (ERK)1/2 and p38 were suppressed by increasing concentrations of
delphinidin. Furthermore, the combination of certain pharmacological inhibitors,
including phosphoinositide 3-kinase (PI3K; LY294002), ERK1/2 (U0126) and
delphinidin significantly reduced the proliferation of SKOV3 cells and the
phosphorylation of each of those target proteins. In addition, delphinidin
treatment exerted anti-proliferative effects on paclitaxel-resistant SKOV3 cells,
compared with treatment with paclitaxel alone. These results indicate that
delphinidin inhibits the proliferation of SKOV3 cells through inactivation of
PI3K/AKT and ERK1/2 mitogen-activated protein kinase signaling cascades, and that
this cell signaling pathway may be a pivotal therapeutic target for the
prevention of epithelial ovarian cancer, including paclitaxel-resistant ovarian
cancer.
PMID- 28693238
TI - Intranuclear accumulation of galectin-3 is an independent prognostic factor for
patients with distal cholangiocarcinoma.
AB - Galectin-3 has been reported to be associated with the prognosis of patients with
various malignancies; however, it has not yet been investigated in patients with
extrahepatic cholangiocarcinoma (EHCC). Expression of galectin-3 was
retrospectively examined in 58 patients with EHCC: 21 with perihilar
cholangiocarcinoma and 37 with distal cholangiocarcinoma (DCC). The Cox
proportional hazard model was used to identify independent prognostic factors.
Intranuclear accumulation of galectin-3 (gal-3-INA) was associated with poorer
overall survival (OS) in all patients (P=0.003), as well as in patients with DCC
(P=0.004). Patients with gal-3-INA also exhibited a poorer disease-free survival
(DFS) than those without gal-3-INA in all patients with EHCC (P<0.001), and in
patients with DCC (P<0.001). Gal-3-INA was an independent prognostic factor of OS
and DFS in all patients [OS: Hazard ratio (HR), 4.470; 95% confidence interval
(CI), 1.759-11.357; P=0.002; and DFS: HR, 5.116; 95% CI, 2.025-12.925; P=0.001].
Gal-3-INA was also an independent prognostic factor in patients with DCC (OS: HR,
2.979; 95% CI, 1.035-8.570; P=0.043; and DFS: HR, 6.773; 95% CI, 1.558-29.439;
P=0.011). In the analysis of patients with DCC, the number of patients with high
galectin-3 expression (P=0.038), recurrence (P<0.001), distant metastases
(P<0.001), R0 status (P=0.029) or microscopic vascular invasion (P=0.019) was
significantly higher in the gal-3-INA-positive group than in the gal-3-INA
negative group. In conclusion, gal-3-INA was identified as a strong prognostic
factor for OS and DFS in patients with DCC.
PMID- 28693239
TI - Biological effects and clinical characteristics of microRNA-106a in human
colorectal cancer.
AB - MicroRNAs serve important roles in various diseases, particularly cancer.
microRNA-106a (miR-106a) exhibits abnormal expression and oncogenic activity in
carcinogenesis. The clinical significance of the abnormal expression of miR-106a
in colorectal cancer is poorly understood. In the present study, miR-106a
expression from colorectal cancer tissues was quantified using the reverse
transcription-quantitative polymerase chain reaction. The overexpression or
knockdown of miR-106a was performed by transfection with microRNA mimic or
inhibitor in human colorectal carcinoma HCT116 cells. The overexpression of miR
106a promoted viability and inhibited apoptosis in colorectal cancer cells. The
association between miR-106a expression and clinicopathological factors was
analyzed, and it was identified that miR-106a exhibited significantly increased
expression in adenocarcinoma tissues compared with in mucinous carcinoma tissues,
and the expression of miR-106a was identified to be associated with the depth of
invasion and differentiation. The expression of miR-106a in plasma was also
determined and it was identified that increased expression of miR-106a, as a
characteristic of patients with colorectal cancer, may be distinguished from that
of other patients by digitization of the areas under the receiver operating
characteristic curves. These data suggested that miR-106a is a potential
biomarker in the diagnosis of colorectal carcinoma. However, the underlying
molecular mechanism of miR-106a-promoted viability and inhibition of apoptosis
requires further investigation.
PMID- 28693240
TI - Melanoma antigen-encoding gene family member A1-6 and hTERT in the detection of
circulating tumor cells following CD45- depletion and RNA extraction.
AB - A total of 76 blood samples from patients without malignant disease and 107 blood
samples from patients with malignant disease were investigated for the presence
of circulating tumor cells (CTCs). To detect CTCs, hematopoietic cells were
removed from the blood samples and different RNA extraction methods were used to
amplify the melanoma antigen-encoding gene family member A1-family member A6
(MAGE A1-6) and the human telomerase reverse transcriptase (hTERT) gene as
potential CTC markers. Comparison between four methods for extracting RNA from
the blood was performed. The samples were enriched by cluster of differentiation
45 (CD45) antibody capturing, and the reverse transcription-quantitative
polymerase chain reaction was used to amplify the MAGE A1-6 and hTERT genes. MAGE
A1-6 and hTERT gene expression levels were also evaluated in 14 cancer cell
lines, and the MAGE A1-6 and hTERT expression levels were 85.7 and 100%,
respectively. The RNeasy method demonstrated the most sensitivity in the SNU1
cells mixed with blood, although the differences between methods was non
significant. The positive expression levels of MAGE A1-6 and hTERT was 11.8% in
the control group and 58.9% in those with malignant disease. In the 70 patients
with colorectal cancer, positive expression levels of MAGE A1-6 or hTERT were
significantly higher in stages T3 and T4 compared with in stages T1 and T2. The
CTC detection method involving CD45 antibody capture, RNA extraction and MAGE A1
6 and hTERT reverse transcription resulted in good rates of sensitivity and
specificity. Thus, the present study concluded that MAGE A1-6 and hTERT genes may
be potential and practical markers for CTCs in a clinical setting.
PMID- 28693241
TI - The novel immunomodulator IMMUNEPOTENT CRP combined with chemotherapy agent
increased the rate of immunogenic cell death and prevented melanoma growth.
AB - Immunogenic cell death is a cell death modality that stimulates the immune system
to combat cancer cells. IMMUNEPOTENT CRP (ICRP) is a mixture of substances of low
molecular weight obtained from bovine spleens that exhibits in vitro cytotoxic
activity on different tumor cell lines and modulates the immune response in vivo.
The aim of the present study was to determine whether the cytotoxic effect of
ICRP and its combination with oxaliplatin (OXP) on murine melanoma B16F10 cells
was due to immunogenic cell death. The cytotoxic assay was performed using flow
cytometry to detect Annexin V and propidium iodide staining, and calreticulin
(CRT) exposure. Adenosine triphosphate, heat shock protein (HSP) 70, HSP90 and
high mobility group box 1 (HMGB1) release were identified using bioluminescence,
western blot and ELISA assays, respectively. The present in vitro study
demonstrated that treatments with ICRP or OXP induced cell death in a time
dependent manner, but treatment with the combination of ICRP + OXP increased the
cytotoxic effect following 24 h of treatment. CRT exposure and release of
adenosine triphosphate (ATP), HSP70, HSP90 and HMGB1 were induced by treatment
with ICRP, and the combination of ICRP + OXP increased the exposure and release
of damage-associated molecular patterns (DAMPs), while OXP treatment only induced
CRT exposure, ATP and HMGB1 release. The in vivo experiments demonstrated that
administration of tumor-derived DAMP-rich cell lysates derived from B16F10 cells
treated with ICRP and the combination of ICRP + OXP prevented melanoma growth;
however, OXP treatment did not. These results suggested that IMMUNEPOTENT CRP may
be used as an agent to increase the ability of antitumor drugs to induce
immunogenic cell death and prevent the growth of melanoma.
PMID- 28693242
TI - Bufalin sensitizes human bladder carcinoma cells to TRAIL-mediated apoptosis.
AB - Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), a member
of the TNF superfamily, has garnered interest as it is relatively non-toxic to
normal cells, but selectively induces apoptotic cell death in multiple types of
transformed or malignant cells. Bufalin is the major digoxin-like immunoreactive
component of Sum Su, which is obtained from the skin and parotid venom gland of
the toad. Bufalin is known to inhibit cell proliferation and induce apoptosis in
a variety of cancer cells. The present study investigated whether bufalin
promoted TRAIL-induced apoptotic cell death. In the present study, a combined
treatment using bufalin and TRAIL significantly increased TRAIL-mediated
inhibition of cell viability and increased apoptosis in T24 human bladder cancer
cells. The apoptotic effects were associated with the upregulation of death
receptor proteins and the downregulation of cellular Fas-associated death domain
like interleukin-1beta-converting enzyme inhibitory protein and X-linked
inhibitor of apoptosis protein. Furthermore, the data revealed that bufalin and
TRAIL activated caspase-3, -8 and -9 and subsequently increased the degradation
of poly (ADP-ribose) polymerase. Taken altogether, the nontoxic doses of bufalin
and TRAIL sensitized T24 cells to TRAIL-mediated apoptosis. Therefore, bufalin
may provide an effective therapeutic strategy for the safe treatment of human
bladder cancers that are resistant to TRAIL.
PMID- 28693243
TI - RT-qPCR for PHOX2B mRNA is a highly specific and sensitive method to assess
neuroblastoma minimal residual disease in testicular tissue.
AB - Neuroblastoma (NB) is the most common type of extracranial solid tumor in
children with a high prevalence in toddlers. For childhood cancer survivors,
preservation of reproductive potential is an important factor for quality of
life. The optimization of NB minimal residual disease (MRD) detection in
testicular tissue is crucial to evaluate the risk of malignant cell
reintroduction. The first step in the present study was to assess the accuracy of
reverse transcription-quantitative polymerase chain reaction (RT-qPCR) to detect
tyrosine hydroxylase (TH), paired-like homeobox 2b (PHOX2B) and doublecortin
(DCX) mRNA expression in frozen/thawed testicular tissues of patients with non
obstructive azoospermia (NOA) contaminated (in vitro model) with an increasing
number of IMR-32 and SK-N-SH NB cells. Testicular tissues were frozen by slow or
snap freezing. The second step was to determine the expression levels of these
markers in testicular samples from 4 pre-pubertal males (2 with stage IV NB and 2
with non-NB malignancy). The yield of extracted RNA was similar in testicular
samples frozen by slow or snap freezing. In the in vitro model, TH and DCX
transcripts were detected in uncontaminated testicular tissues, whereas PHOX2B
mRNA was not detected. There was a strong positive association between the number
of NB cells used for contamination and PHOX2B transcript levels. For IMR-32 and
SK-N-SH NB cell lines, specificity and sensitivity rates of detection were 100%
for PHOX2B following in vitro contamination with 10 tumor cells. In testicular
samples from pre-pubertal males with and without NB, PHOX2B mRNA expression was
not observed, but high expression levels of TH and DCX mRNA were detected, which
were similar to expression detected in the in vitro model. Among the markers used
in blood and bone marrow for NB MRD studies, the detection of PHOX2B transcripts
by RT-qPCR may provide an accurate assessment of NB cells in testicular tissues
from males who require fertility preservation.
PMID- 28693244
TI - Improvement of diagnostic efficiency in distinguishing the benign and malignant
thyroid nodules via conventional ultrasound combined with ultrasound contrast and
elastography.
AB - We aimed to evaluate the diagnostic values of conventional ultrasound (US),
ultrasound contrast (UC) and ultrasound elastography (UE) in distinguishing the
benign and malignant thyroid nodules. A total of 100 patients with thyroid
nodules receiving operative treatment were selected; they underwent the
conventional US, UE and UC examinations before operation, respectively. The
nodules received pathological examination after operation to distinguish benign
from malignant lesions. The sensitivity, specificity and diagnostic accordance
rate of each diagnostic method was evaluated by receiver operating characteristic
(ROC) curve, and the area under the curve (AUC) of ROC was calculated. The
manifestations of malignant thyroid nodules in conventional US examination were
mostly the hypoecho, heterogeneous echo, irregular shape, unclear boundary,
aspect ratio <1, microcalcification and irregular peripheral echo halo, and there
were statistically significant differences compared with the benign nodules
(P<0.05). UE showed that the differences between benign and malignant nodules in
2, 3 and 4 points were statistically significant (P<0.05). The manifestations of
malignant nodules in UC were mostly the irregular shape, obscure boundary, no
obvious enhancement, heterogeneous enhancement and visible perfusion defects, and
there were statistically significant differences compared with the benign nodules
(P<0.05). ROC curve showed that both sensitivity and specificity of UE and UC
were superior to those of conventional US. AUC was the largest (AUC = 0.908) and
the diagnostic value was the highest in the conventional US combined with UE and
UC. Conventional US combined with elastography and UC can significantly improve
the sensitivity, specificity and accuracy of diagnosis of benign and malignant
thyroid nodules.
PMID- 28693245
TI - Effects of remifentanil on hemodynamics, liver function and ICAM-1 expression in
liver cancer patients undergoing surgery.
AB - The objective of the present study was to investigate the effects of remifentanil
on hemodynamics, liver function, and expression of intercellular adhesion
molecule-1 (ICAM-1) in patients with liver cancer undergoing surgery. A total of
60 patients who underwent liver cancer resection in The First People's Hospital
of Xiangyang, Hubei University of Medicine from January 2014 to January 2016 were
selected, including 33 males and 27 females, with an average age of 54.12+/-4.77
years. Patients were randomly divided into the control group and experimental
group (n=30 each). The control group and experimental group were anesthetized
with propofol/isoflurane and remifentanil/propofol, respectively. In addition to
general parameters, the following parameters were analyzed: mean systolic blood
pressure and mean diastolic blood pressure were obtained before treatment, during
anesthesia induction and intubation, during blockade of traction reflexes in
surgery, and before extubation at the end of surgery. The recovery time from
anesthesia withdrawal to spontaneous breathing, time of eye opening, time of
extubation, and level of consciousness were recorded. Liver expression of ICAM-1
was measured with SABC staining, and the expression of aspartate aminotransferase
(AST), alanine aminotransferase (ALT), and total bilirubin (TBIL) were recorded
on the first, third, fifth, and seventh day after surgery. According to
hemodynamic parameters, patients in the experimental group experienced a more
stable condition than patients in the control group (P<0.05). In addition, the
recovery time of the experimental group was shorter than that of the control
group (P<0.05). Markers of liver function (AST, ALT and TBIL) of the two groups
after surgery were higher than those before surgery, and the increases of the
experimental group were significantly lower than those of the control group. ICAM
1 expression in the experimental group was significantly lower than in the
control group (P<0.05). In conclusion, anesthesia with remifentanil better
maintained the stability of hemodynamics, played a protective role against
hepatic ischemia-reperfusion injury, and reduced ICAM-1 expression.
PMID- 28693246
TI - Genetic alterations in Japanese extrahepatic biliary tract cancer.
AB - Biliary tract cancer (BTC) is one of the most devastating types of malignant
neoplasms worldwide. However, the mechanisms underlying the development and
progression of BTC remain unresolved. BTC includes extrahepatic bile duct
carcinoma (EBDC), gallbladder carcinoma (GBC) and ampulla of Vater carcinoma
(AVC), named according to the location of the tumor. Although genetic alterations
of intrahepatic cholangiocarcinoma have been investigated, those of EBDC, GBC and
AVC have not yet been fully understood. The present study analyzed somatic
mutations of 50 cancer-associated genes in 27 Japanese BTC cells, including: 11
EBDC, 14 GBC and 2 AVC. Next-generation sequencing using an Ion AmpliSeq Cancer
Panel identified a total of 44 somatic mutations across 14 cancer-associated
genes. Among the 44 mutations, 42 were judged as pathological mutations. Frequent
mutations were identified in tumor protein 53 (TP53) (14/27), SMAD family member
4 (SMAD4) (6/27), phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic
subunit alpha (PIK3CA) (6/27), and Kirsten rat sarcoma (KRAS) (6/27); no
significant differences were identified between EBDC and GBC tissues. Notably,
the frequency of the PIK3CA mutation was higher when compared with previous
reports. This result may suggest that the activation of the PIK3CA-protein kinase
B signaling pathway, in addition to the abrogation of p53, SMAD4 and RAS mitogen
activated protein kinase may have a crucial role in the carcinogenesis of
Japanese BTC. These findings may be useful for the development of personalized
therapies for BTC.
PMID- 28693247
TI - Evaluation of concurrent chemoradiotherapy for locally advanced NSCLC according
to EGFR mutation status.
AB - Concurrent chemoradiotherapy (cCRT) is the standard treatment for patients with
locally advanced non-small cell lung cancer (LA-NSCLC). However, the efficacy and
safety of this treatment has not been compared between patients who possess
epidermal growth factor receptor (EGFR) mutations and patients with wild-type
EGFR. The objective of the present study was to evaluate the effect of the
presence of EGFR gene mutations in patients with LA-NSCLC receiving cCRT. Between
January 2007 and December 2013, the records of 64 patients were reviewed
retrospectively. The data were statistically analyzed to evaluate the efficacy of
cCRT according to EGFR mutation status. In total, 15/64 were revealed to possess
EGFR mutations, 23%, and comprised the mutant EGFR group. The progression-free
survival time was significantly shorter in the mutant EGFR group compared with
the patient group with tumors exhibiting wild-type EGFR, 6.3 and 9.5 months,
respectively (P<0.001). The overall survival rate was longer in the mutant EGFR
group compared with the wild-type EGFR group, although the difference was not
statistically significant, 37.1 and 21.1 months, respectively (P=0.26). The
disease recurred in all of the patients of the mutant EGFR group, whilst the
recurrence rate in the wild-type EGFR group was 89%. The frequency of distant
metastasis was significantly higher in the mutant EGFR group compared with the
wild-type EGFR group. In conclusion, these data suggest that additional studies
are required to identify strategies for reinforcing the efficacy of cCRT, with a
focus on the potential use of EGFR tyrosine kinase inhibitors for patients
exhibiting an EGFR mutation.
PMID- 28693248
TI - Exon 7 splicing variant of estrogen receptor alpha is associated with
pathological invasiveness in smoking-independent lung adenocarcinoma.
AB - Patients with smoking-independent lung cancer mainly consist of females, yet the
molecular background of this epidemiological feature, other than epidermal growth
factor receptor (EGFR) mutation, remains unclear. Several studies have revealed
the association between female hormone-associated factors and the prognosis of
lung cancer, however the data remain inconsistent. The present study focused on
the expression of estrogen receptor (ER)alpha in order to elucidate this
association in smoking-independent lung cancer. Immunohistochemistry staining
(IHC) of aromatase, ERalpha and ERbeta was performed against formalin-treated
tissues from 38 patients who had never-smoked who underwent complete surgical
resection between 2012 and 2013. Among them, adequate RNA of the tumor and
adjacent normal lung cancer was extracted from 31 matching deep frozen samples.
Considering the IHC results, reverse transcription-quantitative polymerase chain
reaction (RT-qPCR) was performed to measure the expression level of 2 different
exons of ERalpha, exon 6 and exon 7, which are part of the ligand binding domain
of ERalpha, using the Taqman gene expression assay. Extra-nuclear expression of
ERalpha using IHC demonstrated a statistically significant association with
pathological invasiveness. RT-qPCR results exhibited a decreased expression of
ERalpha exon 7 in invasive tumor tissues, compared with their adjacent normal
tissues. This is consistent with the findings of previous in vitro studies
indicating that extra-nuclear ERalpha were exon 7 splicing variants. No
difference was observed in ERalpha exon 7 expression between normal and tumor
tissues in non-invasive lung cancer tissues. When considering the EGFR mutation
status, EGFR wild-type lung cancers exhibited decreased ERalpha exon 7 expression
levels compared with EGFR mutated lung cancers. Extra-nuclear expression of
ERalpha, which may represent exon 7 splicing variants of ERalpha, showed
statistical association with pathological invasiveness in smoking-independent
lung cancer. The post-translational splicing mechanism of ERalpha may be involved
in the acquired invasiveness of smoking independent lung cancer.
PMID- 28693249
TI - Hepatocyte selection medium-enriched hepatocellular carcinoma cells are positive
for alpha-fetoprotein and CD44.
AB - Tissues surrounding hepatocellular carcinomas (HCCs) lack glucose. Hepatocyte
selection medium (HSM) is deficient in glucose and is supplemented with
galactose. HCC cells were cultured in HSM to investigate the stem cell markers
alpha-fetoprotein (AFP) and cluster of differentiation 44 (CD44). HCC cells (HLF
and PLC/PRF/5 cells) were cultured in HSM. Viable cell numbers were determined on
days 0 and 7 following culture in HSM. RNA was isolated and subjected to reverse
transcription-quantitative PCR (RT-qPCR) to analyze the mRNA expression levels of
AFP and CD44. Immunostaining was performed to analyze the protein levels of AFP
and CD44. The number of viable cells was significantly decreased on day 7
following culture in HSM. The expression levels of AFP and CD44 increased on day
7 as assessed using RT-qPCR. Immunostaining confirmed the results of RT-qPCR
analysis. The number of viable HCC cells was decreased in HSM, whereas the
expression levels of AFP and CD44 increased. Therefore, HSM is potentially useful
for the enrichment of HCC cells with cancer stem cell characteristics.
PMID- 28693250
TI - Bcl-2/Bcl-xL inhibitor ABT-737 sensitizes pancreatic ductal adenocarcinoma to
paclitaxel-induced cell death.
AB - Pancreatic ductal adenocarcinoma (PDA) is an aggressive malignant disease that is
resistant to various chemotherapeutic agents and commonly relapses. Efficient
elimination of metastasized PDA is critical for a positive post-surgical
treatment outcome. The present study analyzed the effect of the B-cell lymphoma-2
(Bcl-2)/B-cell lymphoma extra-large (Bcl-xL) inhibitor, ABT-737, on paclitaxel
induced PDA cell death. A total of 8 PDA cell lines were subjected to
immunoblotting to compare the expression of Bcl-2/Bcl-xL and other factors
associated with taxane resistance, including myeloid cell leukemia 1 and betaIII
tubulin (TUBB3). The viability of PDA cells was analyzed following treatment with
paclitaxel alone or a combination treatment with ABT-737 and paclitaxel.
Treatment with the ABT-737/paclitaxel combination induced PDA cell death at a
lower concentration of paclitaxel compared with paclitaxel alone. In addition,
the viable cell population at the saturation point of paclitaxel was also
decreased by co-treatment with ABT-737. ABT-737 lowered the half maximal
inhibitory concentration (IC50) by >2-fold in PDA cells with high Bcl-2/Bcl-xL
expression, but not in PDA cells with low Bcl-2/Bcl-xL expression and high TUBB3
expression. Knockdown of Bcl-xL lowered the IC50 of paclitaxel, but knockdown of
TUBB3 did not. ABT-737 sensitized PDA to paclitaxel-induced cell death, and Bcl
xL expression was a key determinant of its sensitivity. ABT-737 is potential
candidate for combination chemotherapy of PDA with high Bcl-xL expression levels.
PMID- 28693251
TI - Clinical features and surgical management of intracranial meningiomas in the
elderly.
AB - Meningioma accounts for ~25% of all primary intracranial neoplasms and the
incidence increases with age. Prvios population-based studies demonstrated that
the annual incidence of intracranial meningiomas was 1.2-3.1/100,000 population.
In particular, the incidence of this disease among the elderly is high. Recently,
increased life expectancy and greater use of diagnostic radiological imaging led
to an increased incidence in the diagnosis of intracranial meningiomas, both
symptomatic and asymptomatic, in the elderly. Thus, neurosurgeons may be
increasingly confronted with the management of intracranial meningiomas in the
elderly. In practice, it is often difficult for physicians to determine whether
traditional surgical resection is the optimal management strategy for
intracranial meningiomas in the elderly. However, reported clinical studies about
the outcome of surgical resection of intracranial meningiomas in the elderly are
limited. Increased risk of mortality and morbidity associated with surgical
treatment for intracranial meningiomas in the elderly compared with younger
patients have been controversial. In the present study, the clinical features of
intracranial meningiomas in 70 consecutive intracranial meningioma patients that
underwent surgical treatment at the affiliated hospital of University of
Occupational and Environmental Health between 2007 and 2013 were assessed. In
addition, patient selection and surgical management of intracranial meningioma in
elderly patients was discussed. Preoperative factors, including symptoms, tumor
location, tumor size, Karnofsky Performance Scale (KPS) score and American
Society of Anesthesiology (ASA) score, and postoperative factors, including
pathological diagnosis, tumor proliferation index (Ki-67), resection rate
(Simpson grade), length of hospital stay and discharge destination were
retrospectively analyzed in patients aged >=75 years (n=16; elderly group) and
<75 years (n=54; younger group). Outcomes were assessed 6 months after surgery.
Multivariate logistic regression revealed that tumor resection rate (Simpson
grade III-V) was an important predictor of surgical complications (odds ratio,
5.662; 95% confidence interval, 1.323-24.236; P=0.0194). Perioperative morbidity
was not correlated with age (>75 years), tumor location, tumor size, KPS score or
ASA score. Thus, the present study indicated that age is not associated with
surgical outcome in elderly meningioma patients. Regardless of patient age, the
decision to perform surgical resection should be made on an individual basis
wherein tumor characteristics and the general health of the patient are
considered.
PMID- 28693252
TI - Clinical outcomes of percutaneous radiofrequency ablation for small renal cancer.
AB - Partial nephrectomy is the treatment of choice for small renal cell carcinoma
(RCC) from the perspective of cancer management and renal function. However, when
patients with RCC are of advanced age, exhibit severe comorbidities, including
cardiovascular and pulmonary diseases, or have hereditary RCC, ablative
therapies, including radiofrequency ablation (RFA) and cryoablation are useful
treatment options. In the present study, the clinical outcomes of percutaneous
RFA for treating small RCC were evaluated. Between December 2005 and March 2015,
40 patients (41 renal tumors in total) underwent RFA and a total of 50 sessions
of RFA were performed. The average tumor size was 2.5 cm. A total of 18 tumors
were exophytic and 23 were parenchymal. Of the 41 tumors, 85.4% were completely
ablated by initial RFA and the rate of complete ablation following reablation for
residual viable lesions was 95.1%. Local recurrence-free survival following
complete ablation was 84.2% at 3 years. A patient with a 4.7 cm RCC tumor rapidly
progressed following four RFA treatments until complete ablation was achieved.
The metastasis-free survival rate following initial RFA was 95.7% at 3 years. The
RCC-specific survival was 100% (mean follow-up, 38 months). Adverse events
occurred in five sessions (10%); however, only 1 patient with arteriovenous
fistula required intervention (transarterial embolization). The mean hospital
stay following RFA was 3.2 days. The mean decrease in estimated glomerular
filtration rate following RFA was 2.7%. The results of the present study indicate
that percutaneous RFA was an effective treatment for small RCCs with respect to
management of cancer, minimal invasiveness and minimal loss of renal function,
particularly in patients for whom surgery would be a high risk and those at
increased risk of deterioration of renal function.
PMID- 28693253
TI - Telomere length is correlated with mitochondrial DNA copy number in intestinal,
but not diffuse, gastric cancer.
AB - A positive correlation between telomere length and mitochondrial DNA (mtDNA) copy
number has previously been observed in healthy individuals, and in patients with
psychiatric disorders. In the present study, telomere length and mtDNA copy
number were evaluated in gastric cancer (GC) tissue samples. DNA was extracted
from 109 GC samples (including 82 intestinal, and 27 diffuse cases), and the
telomere length and mtDNA copy number were analyzed using a quantitative
polymerase chain reaction assay. The relative telomere length and mtDNA copy
number in tumor tissue, as compared with in normal tissue, (mean +/- standard
deviation) in all GC samples were 11.48+/-1.14 and 14.86+/-1.35, respectively.
Telomere length and mtDNA copy number were not identified as exhibiting clinical
or prognostic value for GC. However, positive correlations between telomere
length and mitochondrial DNA copy number were identified in GC (r=0.408, P<0.001)
and in the adjacent normal mucosa (r=0.363; P<0.001). When stratified by Lauren
classification, the correlation was identified in intestinal type GC samples
(r=0.461; P<0.001), but not in diffuse type GC samples (r=0.225; P=0.260). This
result indicated that loss of the correlation of telomeres and mitochondrial
function may induce the initiation or progression of GC pathogenesis.
PMID- 28693254
TI - Elevated levels of mRNAs encoding dihydropyrimidine dehydrogenase and thymidylate
synthase are associated with improved survival of patients with hepatocellular
carcinoma treated with S-1.
AB - Thymidylate synthase (TYMS) and dihydropyrimidine dehydrogenase (DPYD) are
associated with the response of tumors to fluoropyrimidines. The aim of the
present study was to investigate the association between the levels of TYMS and
DPYD mRNAs and the efficacy of S-1 for treating patients with HCC. A total of 35
patients with HCC who received S-1 upon recurrence (S-1 group) and 20 patients
who never received a fluoropyrimidine (control group) were studied. The levels of
TYMS and DPYD mRNA in surgically resected specimens were determined using reverse
transcription-polymerase chain reaction assays. Overall survival (OS) time of S-1
group patients with high levels of DPYD mRNA was significantly longer compared
with that of patients with low levels (median 501 days vs. 225 days; P=0.016).
Similarly, the OS time of those patients with high levels of TYMS mRNA was
significantly longer compared with those with low levels (median 503 days vs. 239
days; P=0.0076). By contrast, there was no difference in OS time of the control
group between patients with high and low levels of DPYD and TYMS mRNAs. The
levels of TYMS and DPYD mRNAs may serve as predictive markers for patients with
HCC who receive S-1 chemotherapy.
PMID- 28693255
TI - Sodium butyrate enhances the growth inhibitory effect of sunitinib in human renal
cell carcinoma cells.
AB - Sunitinib (SU) is a small molecule that inhibits the receptor tyrosine kinase
(RTK) signaling pathway, and has been clinically used to treat advanced renal
cell carcinoma (RCC). However, SU is not always effective as RCC is a highly
chemoresistant type of cancer. One of the factors that confer chemoresistance to
RCC is a hypoxic condition. Lack of oxygen activates hypoxia-inducible factor
(HIF) protein, which is followed by the upregulation of growth factors, including
vascular endothelial growth factor and activation of the RTK signaling pathway.
In this context, histone deacetylase inhibitors (HDACIs) are considered prominent
combined agents for SU as they downregulate the expression of HIFs. Therefore,
the present study aimed to investigate the effectiveness of combined treatment
with SU and sodium butyrate (NaBu), an HDACI. Long-term exposure to these agents
exerted a stronger growth inhibitory effect in RCC cell lines compared with
single treatment groups. Furthermore, combined treatment suppressed HIF-2alpha
protein, which was induced under hypoxic conditions. In addition, this
combination sustained the activity of the RTK signaling pathway to the level of
intact cells, although a single treatment with SU or NaBu was demonstrated to
increase this activity. Overall, it is suggested that the combination of SU and
NaBu is effective for overcoming drug resistance in RCC.
PMID- 28693256
TI - Pirfenidone may revert the epithelial-to-mesenchymal transition in human lung
adenocarcinoma.
AB - The epithelial-to-mesenchymal transition (EMT) in cancer is associated with
invasion, metastasis and chemoresistance. Recent studies have revealed the
increased expression of programmed death-ligand 1 (PD-L1) in cells undergoing
EMT. The underlying mechanism of EMT involves transforming growth factor-beta
(TGF-beta) and fibroblast growth factor-2 (FGF-2). Pirfenidone and the known EMT
suppressor nintedanib suppress pulmonary fibrosis partially through suppression
of TGF-beta. The present study aimed to determine whether pirfenidone has the
potential to induce EMT-reversion, using nintedanib as a reference. The human
lung adenocarcinoma cell lines A-549, HCC-827, and PC-9 were treated with TGF
beta and FGF-2 to induce EMT. The EMT-induced cells were further treated with
pirfenidone or nintedanib. Phenotypic alterations associated with EMT were
assessed by examining the following: i) The expression levels of E-cadherin,
vimentin, fibronectin and slug, using reverse transcription-quantitative
polymerase chain reaction (RT-qPCR) and fluorescent immunohistochemistry; ii)
cell motility via wound-healing assays; and iii) the expression of PD-L1 using RT
qPCR. The combination of TGF-beta and FGF-2 successfully induced EMT in all three
cell lines, characterized by a significant reduction in E-cadherin expression in
the A-549 and HCC-827 cells, increased expression levels of vimentin,
fibronectin, slug and PD-L1, and increased cell motility in all three cell lines.
Pirfenidone and nintedanib reverted all of these phenotypes, with the exception
of unaltered E-cadherin expression in all three cell lines, and inconsistent
expression of vimentin in the HCC-827 and PC-9 cells. Thus, pirfenidone and
nintedanib have the ability to induce EMT-reversion in human lung adenocarcinoma.
PMID- 28693257
TI - UCP2 expression may represent a predictive marker of neoadjuvant chemotherapy
effectiveness for locally advanced uterine cervical cancer.
AB - Concurrent chemoradiotherapy is the standard treatment for locally advanced
uterine cervical cancer. However, effective neoadjuvant chemotherapy (NAC) can
reduce tumor size and facilitate hysterectomy for locally advanced uterine
cervical cancer. NAC treatment could improve the prognosis of patients with
locally advanced cervical cancer. However, if NAC is ineffective, radiotherapy
must be pursued. This causes a delay in initiating the core treatment and results
in a worse prognosis. Therefore, the identification of predictive markers of
whether NAC is likely to be effective for the treatment of locally advanced
uterine cervical cancer could improve patient prognosis. Uncoupling protein 2
(UCP2) is broadly expressed in cancer cells, and suppresses mitochondrial
reactive oxygen species (ROS) production. UCP2 contributes to both carcinogenesis
and chemoresistance by reducing ROS. Downregulation of UCP2 results in
significantly increased cell death following chemotherapy. The present study
investigated the association between UCP2 expression and NAC effectiveness. A
total of 58 patients with locally advanced uterine cervical cancer (stage IIIA or
IIIB) treated at Osaka City University Hospital between April 1995 and March 2010
were examined. Tumor tissue samples were obtained by punch biopsy prior to NAC.
UCP2 expression was examined immunohistochemically and scored using a weighted
scoring system. Patients were divided into NAC effective (n=34) and ineffective
(n=24) groups. Furthermore, UCP2 expression in human uterine cervical cancer
cells was inhibited by genipin, and changes in cisplatin sensitivity were
examined. UCP2 weighted score was higher in the NAC ineffective group than in the
NAC effective group (P=0.038). Additionally, the low UCP2 expression group was
more sensitive to NAC than the high UCP2 expression group (P=0.041). Sensitivity
to cisplatin was significantly increased when UCP2 was inhibited in human uterine
cervical cancer cells in vitro. UCP2 expression may become a predictive marker of
whether NAC is effective for patients with locally advanced uterine cervical
cancer, which could improve patient prognosis.
PMID- 28693258
TI - MLH1 expression predicts the response to preoperative therapy and is associated
with PD-L1 expression in esophageal cancer.
AB - Programmed death-ligand 1 (PD-1/PD-L1) inhibition therapy demonstrates potential
as a future treatment for esophageal cancer. Mismatch repair status and tumor PD
L1 expression are the candidate predictive biomarkers for response to this
therapy. In colorectal cancer, mismatch repair-deficient tumors are associated
with improved survival, although they are not sensitive to 5-fluorouracil-based
chemotherapy. The purpose of the present study was to investigate the association
between MutL homolog 1 (MLH1) expression and prognosis, response to therapy and
PD-L1 expression in esophageal cancer. Immunohistochemistry was used to evaluate
MLH1 and PD-L1 expression in 251 resected specimens. Of the specimens, 30.3%
exhibited low MLH1 expression and 15.5% exhibited high PD-L1 expression. The 5
year overall survival rates for the high MLH1 expression group and the low MLH1
expression group were 51.3 and 55.6%, respectively (P=0.5260). The responder
ratio was 45.7% in the high MLH1 expression group and 15.4% in the low MLH1
expression group (P<0.0001). The frequency of high PD-L1 expression was 11.4% in
the high MLH1 expression group (P=0.0064) and 25.0% in the low MLH1 expression
group. MLH1 expression may be a predictive factor for the response to
preoperative therapy in esophageal cancer, and esophageal cancer with low MLH1
expression may have a mechanism that assists in promoting tumor PD-L1 expression.
PMID- 28693259
TI - RKTG overexpression inhibits proliferation and induces apoptosis of human
leukemia cells via suppression of the ERK and PI3K/AKT signaling pathways.
AB - Raf kinase trapping to Golgi (RKTG) is reported to be a tumor suppressor in a
number of solid tumors due to its negative modulation of the Ras/Raf/mitogen
activated protein kinase kinase/extracellular signal-regulated kinase (ERK)
pathways. However, the role of RKTG in the progression of leukemia remains
unknown. In the present study, a human leukemia U937 cell line overexpressing
RKTG was established, and the effect of RKTG on proliferation, cell cycle and
apoptosis of human leukemia cells was analyzed. The results of the present study
demonstrated that exogenous overexpression of RKTG significantly inhibited cell
proliferation, which was accompanied by cell cycle arrest. Apoptosis assay and
Hoechst staining demonstrated that the percentage of apoptotic cells in RKTG
overexpressing cells was markedly increased. Furthermore, western blotting showed
that RKTG overexpression significantly increased the level of cleaved caspase 3,
B-cell lymphoma 2 (Bcl2)-associated X apoptosis regulator and reduced the level
of Bcl-2. In addition, the activation of ERK and phosphoinositide 3-kinase
(PI3K)/AKT serine/threonine kinase 1 signaling pathways in human leukemia cells
was also suppressed by RKTG overexpression. In conclusion, the present study
demonstrated the tumor-suppressive effect of RKTG on human leukemia cells, which
seem to be partially dependent on the suppression of ERK and PI3K/AKT signaling.
Overexpression of RKTG may be a potential therapeutic target for the treatment of
leukemia.
PMID- 28693260
TI - MicroRNA expression profiling in patients with hepatocellular carcinoma of
familial aggregation and hepatitis B virus infection.
AB - Numerous studies have suggested that microRNAs (miRNAs) potently affect
hepatocarcinogenesis. However, the miRNA expression profiling in patients with
hepatocellular carcinoma (HCC) of familial aggregation and hepatitis B virus
(HBV) infection has not been elucidated. In the present study, the plasma miRNA
expression profiles of 3 patients with HCC with familial aggregation of HCC and
HBV infection and 1 healthy volunteer were examined by microarray analysis, in
order to identify relevant miRNAs involved in the pathogenesis of HCC with
familial aggregation and HBV infection. The results indicated that 26 miRNAs
exhibited a >=20-fold increase or decrease in the plasma of patients with HCC,
compared with the healthy control (24 upregulated and 2 downregulated). Among
these altered miRNAs, 15 of them have been reported in HCC. The other 11 miRNAs
have never been reported in HCC. These differentially-expressed miRNAs may be
potential molecular markers for HCC pathogenesis and development.
PMID- 28693261
TI - Leiomyosarcoma of the splenic vein: A case report.
AB - Leiomyosarcomas (LMSs) originating from the wall of blood vessels are aggressive
and rare neoplasms. The current study describes a case of a 52-year-old man who
presented with intermittent abdominal pain without weight loss or diarrhea.
Computed tomography of the abdomen identified a 4-cm, solid, heterogeneous tumor
in the tail of the pancreas, while a hypodense lesion was also noted in the right
hepatic lobe. The patient subsequently underwent splenic pedicle tumor resection,
splenectomy and liver tumor resection. Notably, immunohistochemical and
histological analyses identified LMS, which had originated from the smooth muscle
of the splenic vein. Currently available information regarding LMSs of the
splenic vein and their management is also discussed, with the aim of improving
diagnostic accuracy.
PMID- 28693262
TI - AXIN1 protects against testicular germ cell tumors via the PI3K/AKT/mTOR
signaling pathway.
AB - Axis inhibition protein 1 (AXIN1) is characterized as a tumor suppressor in
numerous types of cancer. However, the functional role of AXIN1 in the testicular
germ cell tumors (TGCTs) remains unclear. The human embryonal carcinoma-derived
cell line NTera2 was transfected with a recombinant AXIN1 expression vector
(pcDNA3.1-AXIN1) and/or a small interfering RNA (siRNA) directed against AXIN1
(siAXIN). Following transfection, the mRNA and protein levels of AXIN1 were
determined via reverse transcription-quantitative polymerase chain reaction
analysis and western blotting, respectively. In addition, cell viability,
apoptosis and the expression of apoptosis-associated proteins [apoptosis
regulator Bax (Bax) and B-cell lymphoma (Bcl)-2] and phosphatidylinositol 3
kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR)
signaling pathway proteins [phosphorylated (p)-mTOR, mTOR, p-AKT, AKT, P-70S
ribosomal protein S6 (S6) and S6] were assessed. AXIN1 mRNA and protein levels
were increased following transfection with pcDNA3.1-AXIN1 and decreased following
transfection with siAXIN1 compared with their respective control groups. After
overexpression of AXIN1, NTera2 cell viability and expression of Bcl-2, p-mTOR p
AKT and p-S6 protein was decreased, while apoptosis and Bax protein levels were
increased, compared with the control group. However, there was no significant
difference in AXIN1 mRNA expression, apoptosis or Bax/Bcl-2 protein expression
when NTera2 cells were simultaneously transfected with pcDNA3.1-AXIN1+siAXIN1. In
conclusion, the results of the present study indicate that overexpression of
AXIN1 protects against TGCTs via inhibiting the PI3K/AKT/mTOR signaling pathway,
suggesting that AXIN1 may be a potential target for gene therapy in TGCTs.
PMID- 28693263
TI - Role of microRNA-296-3p in the malignant transformation of sinonasal inverted
papilloma.
AB - Inverted papilloma (IP) is a benign tumor occurring in the nasal cavity and
paranasal sinuses. It is reported that 5-15% of IPs undergo malignant
transformation into squamous cell carcinoma (SCC), and the role of microRNAs
(miRNA/miR) in this process remains to be elucidated. In the present study, whole
miRNA profiles using samples of IP and SCC were investigated, in order to detect
the function of miRNA in the carcinogenesis of IP. Samples from IPs (n=5) and SCC
lesions (n=5), which arose from IPs, were used for miRNA analysis. A total of 200
miRNAs exhibited a >2-fold differential expression between IP and SCC. miR-296-3p
was markedly upregulated in SCC with a 23-fold difference. Computational analysis
indicated that miR-296-3p targeted PTEN, which regulates the phosphoinositide 3
kinase (PI3K)/protein kinase B (Akt) signaling pathway and PTEN is involved in
the carcinogenesis of SCC. miR-296-3p directly regulated PTEN expression in head
and neck cancer cells, with PTEN protein levels decreased in 4/19 the SCCs
(21.0%), as compared with those in the IPs (76.4%). Positive p21 staining was
observed in 64.7% of IPs; this was a significantly increased rate compared with
that for SCCs (26.3%, P=0.0086). The results of the present study indicated that
there were marked changes in the miRNA expression signature during the malignant
transition. miR-296-3p may serve an important role in the malignant
transformation of IPs via the regulation of PTEN, combined with the subsequent
inhibition of the PI3K/Akt signaling pathway, and may be a novel agent for cancer
prevention.
PMID- 28693264
TI - Dermatofibrosarcoma protuberans of the breast: A case report.
AB - Dermatofibrosarcoma protuberans (DFSP) is a rare malignant tumor of subcutaneous
tissue characterized by slow infiltrative growth. The tumor occurs in patients of
all ages, with the highest frequency occurring between the second and the fifth
decades of age. Genetically, DFSP is characterized by a reciprocal translocation
t(17;22)(q22;q13), or more often, as a supernumerary ring chromosome involving
chromosomes 17 and 22. Standard treatment of a localized tumor is surgical
excision with wide margins. In the present study, a case report of a 43-year-old
woman with a growing tumor in the left breast is discussed. The patient underwent
breast-conserving surgery. Histological and cytogenetic examinations of the tumor
resulted in a diagnosis of DFSP. The clinical and morphological characteristics
of the tumor, in addition to the treatment options, were also evaluated.
PMID- 28693265
TI - Overexpression of the transmembrane protein BST-2 induces Akt and Erk
phosphorylation in bladder cancer.
AB - Bladder cancer, the majority of which is urothelial carcinoma (UC), is a common
malignancy worldwide. Genes encoding transmembrane/secretory proteins expressed
specifically in certain cancers may be ideal biomarkers for cancer diagnosis and
may represent therapeutic targets. In the present study, the expression and
function of the bone marrow stromal cell antigen 2 (BST2) gene was analyzed in
UC. Reverse transcription-quantitative polymerase chain reaction demonstrated
that expression of BST2 in normal tissue samples was the highest in liver tissue.
However, expression of BST2 in UC tissue samples was higher than in normal liver.
Immunohistochemical analysis revealed weak or no staining of BST-2 in non
neoplastic mucosa, whereas UC tissue exhibited stronger and more extensive
staining compared with non-neoplastic mucosa. BST-2 staining was observed mainly
on UC cell membranes. In total, 28 (41%) of 69 UC cases were positive for BST-2.
UC cases positive for BST-2 were more frequently T2/3/4 cases [so-called muscle
invasive bladder cancer (MIBC)] than Ta/is/1 cases (P=0.0001). However, Kaplan
Meier analysis demonstrated no association between BST-2 expression and survival.
BST2 small interfering RNA (siRNA)-transfected T24 cells exhibited significantly
reduced cell growth relative to negative control siRNA-transfected T24 cells. The
levels of phosphorylated Akt and extracellular signal-regulated kinase were lower
in BST2 siRNA-transfected T24 cells than in control cells. These results suggest
the involvement of BST-2 in the pathogenesis of UC. Since BST-2 is expressed on
the cell membrane, BST-2 may be a good therapeutic target for MIBC.
PMID- 28693266
TI - Knockdown of GluA2 induces apoptosis in non-small-cell lung cancer A549 cells
through the p53 signaling pathway.
AB - alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors are
important glutamatergic receptors that mediate fast excitatory synaptic
transmission in the brain. Previous studies have demonstrated that glutamate
ionotropic receptor AMPA type subunit 2 (GluA2), one of the four subunits that
comprise AMPA receptors, is a potential novel marker for poor prognosis in
patients with human lung cancer. However, the mechanisms of GluA2-induced
apoptosis, proliferation and migration in lung cancer remain unknown. The present
study aimed to explore the mechanisms underlying these effects of GluA2 in human
lung cancer by silencing GluA2 in A549 cells. Using the Cell Counting Kit-8
assay, western blot analysis and acridine orange/ethidium bromide staining,
downregulation of GluA2 was revealed to significantly inhibit the proliferation
and significantly promote the apoptosis of A549 cells. Knockdown of GluA2 was
also revealed to be associated with increased caspase-3 activity, increased Bcl-2
associated X protein and Bcl-2-associated death promoter (Bad) expression, and
decreased expression of B-cell lymphoma-2, p-Bad and X-linked inhibitor of
apoptosis protein. In addition, GluA2 silencing upregulated cellular tumor
antigen p53 (p53)/p21Cip1/Waf1/p16INK4a protein. In conclusion, these results
indicate that the effects of GluA2 in lung cancer are mediated by the caspase-3
and p53/p21Cip1/Waf1/p16INK4a signaling pathways. Therefore, GluA2 may be a
potential novel therapeutic target for the treatment of lung cancer.
PMID- 28693267
TI - Expression of survivin, MUC2 and MUC5 in colorectal cancer and their association
with clinicopathological characteristics.
AB - Survivin is a bifunctional protein that suppresses apoptosis and regulates cell
division, and is highly expressed in various cancer types. Mucins are high
molecular-weight, heavily glycosylated proteins. In the present study, the
association between survivin, mucin 2 (MUC2) and MUC5 expression, and the
clinicopathological features of colorectal cancer (CRC) were investigated. The
immunohistochemistry and western blotting results demonstrated that survivin was
highly expressed in CRC tissues and rarely expressed in normal colon tissues.
Moreover, the overexpression of survivin and MUC5 was strongly associated with
lymph node metastasis, poor cellular differentiation, advanced tumor stage and a
poor prognosis in CRC. By contrast, low expression of MUC2 was significantly
associated with lymph node metastasis, poor cellular differentiation and an
advanced tumor stage in CRC. The results of the present study suggest that
survivin, MUC2 and MUC5 levels may be associated with tumor progression and could
be used to aid the early diagnosis and clinical characterization of CRC.
PMID- 28693268
TI - Clinical diagnosis and detection of genetic mutations of pancreatic metastases: A
report of four cases and review of the literature.
AB - The present study aimed to report our clinical experience regarding the diagnosis
and detection of genetic mutations of pancreatic metastases, and to review the
relevant literature to expand knowledge of this disease. A total of 4 cases
involving pancreatic metastases, which were treated at The First Affiliated
Hospital of Soochow University between January 2013 and July 2016, were
retrospectively analyzed. This retrospective study considered the
clinicopathological variables of the 4 patients, and compared this data with
those from the literature, which was searched using PubMed, EMBASE and the
Cochrane Library. All 4 patients with pancreatic metastases were diagnosed by
computed tomography (CT) scan and confirmed by pathological staining and
immunohistochemistry. Mutation analysis was performed in 3 patients to obtain
precise mutation information for guiding and evaluating the use of molecularly
targeted drugs. In summary, pancreatic metastases are rare and the majority of
pancreatic metastases develop from renal cell carcinoma. Diagnoses of pancreatic
metastases predominantly rely on CT, pathology and immunohistochemistry.
Detection of mutations has clinical value in auxiliary diagnosis and therapy of
pancreatic metastases. Based on mutation information, molecularly targeted drugs
may prolong the survival of patients with unresectable pancreatic metastases.
PMID- 28693269
TI - Significance of E-cadherin and CD44 expression in patients with unresectable
metastatic colorectal cancer.
AB - The loss of adhesion molecules is reported to be associated with tumor invasion
and metastasis in numerous types of cancer. Epithelial (E)-cadherin is an
important molecule for cell-to-cell adhesion, while cluster of differentiation
(CD)44 is an important molecule for cell-to-extracellular matrix adhesion. The
focus of the present study was to evaluate the significance of the expression of
E-cadherin and CD44 in patients with the unresectable metastatic colorectal
cancer (CRC) who are undergoing palliative chemotherapy. Formalin-fixed, paraffin
embedded samples were obtained from 49 patients who underwent primary tumor
resection and who were receiving palliative chemotherapy for unresectable
metastatic CRC. The expression of E-cadherin and CD44 was evaluated using
immunohistochemistry. The expression of E-cadherin was not significantly
associated with progression-free survival (PFS; P=0.2825) or overall survival
(OS; P=0.6617). The expression of CD44 was not associated with PFS (P=0.4365),
but it did exhibit a certain level of association with OS (P=0.0699). However,
the combined low expression of E-cadherin and CD44 demonstrated a significant
association with decreased PFS (P=0.0101) and OS (P=0.0009). The combined loss of
E-cadherin and CD44 expression also led to a reduction in the objective response
rate and disease control rate (P=0.0076 and P=0.0294, respectively). A univariate
analysis indicated that the combined low expression of E-cadherin and CD44
(P=0.0474) and sex (P=0.0330) were significantly associated with decreased PFS,
and multivariate analysis confirmed combined low expression of E-cadherin and
CD44 as an independent risk factor for decreased PFS [hazard ratio (HR), 8.276;
95% confidence interval (CI), 1.383-43.311; P=0.0227]. Univariate and
multivariate analyses also indicated that the combined low expression of E
cadherin and CD44 expression was a significant prognostic factor for poor OS (HR,
15.118; 95% CI, 2.645-77.490; P=0.0039). Therefore the current study suggests
that the combined low expression of E-cadherin and CD44 is an effective
independent predictor of decreased chemotherapeutic outcome and survival in
patients with unresectable metastatic CRC.
PMID- 28693270
TI - Hyperthermia and radiation reduce the toxic side-effects of bufadienolides for
cancer therapy.
AB - Bufadienolides are constituents of the traditional Chinese medicine Chan Su and
are found in toad venom. Cardiovascular side-effects are one of the limiting
factors towards developing bufadienolides as chemotherapeutic agents. Thus, in
the present study, low doses of bufalin and cinobufotalin, prominent members of
the bufadienolides, were investigated for their cytotoxic activity in combination
with hyperthermia (HT) or radiation (Rad) therapy. In addition, the underlying
mechanism involved was investigated. A DNA fragmentation assay, viability assay
and microscopic observation were primarily used to assess the effect of low doses
of the two drugs in human lymphoma U937 cells. Furthermore, the effects of these
drugs on the mitochondrial membrane potential (MMP) and apoptotic-associated
protein activation were investigated. HT/bufadienolide- and RT/bufadienolide
treated samples significantly increased the DNA fragmentation percentile and
decreased the MMP, as well as increasing the apoptotic features observed
microscopically within a relatively short time (6 h) after treatment. The two
combinations affected the expression of important apoptotic markers, including
caspase-3 and BH3 interacting domain death agonist. The findings of the current
study confirm the additive effect of HT with this group of drugs, directing a
novel therapeutic avenue for the clinical use of bufadienolides at lower doses
with more restrained cardio toxic side-effects.
PMID- 28693271
TI - Expression of tumor suppressor REIC/Dkk-3 by a newly improved adenovirus vector
with insertion of a hTERT promoter at the 3'-side of the transgene.
AB - Reduced expression in immortalized cells (REIC)/Dickkopf-3 (Dkk-3)
overexpression, induced using an adenovirus (Ad)-REIC, has been revealed to have
a dramatic therapeutic effect on multiple types of cancer. To achieve an improved
therapeutic effect from Ad-REIC on cancer, our group previously developed an
enhanced gene expression system, the C-TSC cassette [cytomegalovirus (CMV)-RU5'
located upstream (C); another promoter unit composed of triple tandem promoters,
human telomerase reverse transcriptase (hTERT), simian virus 40 and CMV, located
downstream of the cDNA (TSC); plus a polyadenylation (polyA) signal]. When
applied to the conventional Ad-REIC, this novel system induced the development of
an enhanced product, Ad-C-TSC-REIC, which exhibited a noticeable anticancer
effect. However, there were difficulties in terms of Ad-C-TSC-REIC productivity
in HEK293 cells, which are a widely used donor cell line for viral production.
Productivity of Ad-C-TSC-REIC was significantly reduced compared with the
conventional Ad-REIC, as the Ad-C-TSC-REIC had a significantly higher ability to
induce apoptotic cell death of not only various types of cancer cell, but also
HEK293 cells. The present study aimed to overcome this problem by modifying the C
TSC structure, resulting in an improved candidate: A C-T cassette (C: CMV-RU5'
located upstream; T: another promoter unit composed of a single hTERT promoter,
located downstream of the cDNA plus a polyA signal), which demonstrated gene
expression comparable to that of the C-TSC system. The improved adenovirus
REIC/Dkk-3 product with the C-T cassette, named Ad-C-T-REIC, exhibited a higher
expression level of REIC/Dkk3, similar to that of Ad-C-TSC-REIC. Notably, the
vector mitigated the cell death of donor HEK293 cells, resulting in a higher rate
of production of its adenovirus. These results indicated that Ad-C-T-REIC has the
potential to be a useful tool for application in cancer gene therapy.
PMID- 28693272
TI - Metformin enhances the cytotoxicity of 5-aminolevulinic acid-mediated
photodynamic therapy in vitro.
AB - The biguanide metformin is a drug widely used for the treatment of type 2
diabetes. Metformin enhances the cytotoxicity of chemotherapy by promoting the
adenosine monophosphate-activated protein kinase (AMPK) autophagy signaling
pathway. Photodynamic therapy (PDT) with 5-aminolevulinic acid (5-ALA), a
precursor of protoporphyrin IX (PpIX), leads to apoptosis when PpIX accumulates
in the mitochondria, and also leads to autophagy through activation of AMPK. In
the present study, the effect of metformin in combination with 5-ALA-PDT was
evaluated in vitro in KLN205 lung cancer cells. At a fluence of 5 J/cm2, 5-ALA
PDT in combination with 5 mM metformin exhibited significantly increased
cytotoxicity compared with that observed with 0 and 0.1 mM metformin (P=0.0197
and P=0.0423, respectively). The cells treated with 5-ALA-PDT and metformin
exhibited condensation of nuclear chromatin and the presence of autophagosomes.
These results indicate that apoptosis and autophagy occur in KLN205 cells
following combined treatment with 5-ALA-PDT and metformin. The results from the
present study are the first to indicate, to the best of our knowledge, that
metformin potentiates the efficacy of 5-ALA-PDT.
PMID- 28693273
TI - Overexpression of mir-183 and mir-494 promotes proliferation and migration in
human breast cancer cell lines.
AB - Breast cancer (BC) is a leading cause of cancer-associated mortality in females
worldwide. MicroRNAs (miRNAs or miRs), a type of non-coding RNA, have been
reported to be important in the regulation of BC onset and progression. Several
studies have implicated the role of miR-183 and miR-494 in different types of
cancer. However, the biological functions of these miRNAs in BC remain largely
unknown. In the present study, the expression of both miRNAs was assessed in the
MDA-MB-231 and MDA-MB-468 BC cell lines. It was hypothesized that miR-183 and miR
494 serve an important role in regulating the expression of key genes associated
with the metastatic phenotype of BC cells. To further understand their role, the
expression of these miRNAs was restored in selected BC cell lines. Functional
assays revealed that overexpression of miR-183 or miR-494 modulated the
proliferation and migration of MDA-MB-231 and MDA-MB-468 cells in vitro.
Additionally, retinoblastoma 1 (RB1) was identified to be a downstream target of
both miRNAs by in silico analysis. Western blotting revealed that upregulation of
miR-183 was associated with downregulation of RB1 protein in MDA-MB-231 cells. In
conclusion, the present results support the hypothesis that miR-183 and miR-494
serve a pivotal role in BC metastasis, and that miR-183 may act as an oncogene by
targeting RB1 protein in MDA-MB-231 cells.
PMID- 28693274
TI - Decreased expression of miR-193a-3p is associated with poor prognosis in
colorectal cancer.
AB - Epithelial-mesenchymal transition (EMT) is an early and key process in the
metastatic cascade during the progression of colorectal cancer (CRC). The aim of
the present study was to identify deregulated EMT-related microRNAs (miRNAs/miRs)
of CRC and assess the effect of differentially expressed miRNAs on the prognosis
of patients with CRC. Genome-wide expression profiling of miRNAs was assessed in
3 EMT-negative and 3 EMT-positive CRC tissues. Differentially expressed miRNA was
further validated in 90 pairs of CRC and corresponding paracarcinoma tissues
using the reverse transcription-quantitative polymerase chain reaction (RT-qPCR).
A total of 6 miRNAs (miR-10a-5p miR-204-3p, miR-1224-3p, miR-193a-3p, miR-365a-3p
and miR-3678-3p) were identified to be differentially expressed between different
EMT statuses of CRC tissues. Following validation using RT-qPCR, 3 miRNAs (miR
10a-5p, miR-365a-3p and miR-193a-3p) were selected for subsequent studies. The
expression levels of miR-10a-5p, miR-193a-3p and miR-365a-3p were markedly
increased compared with levels in corresponding paracarcinoma tissues. Survival
analyses revealed that down-regulation of miR-193a-3p was associated with worse
prognosis of patients with CRC, particularly in female and older patients. The
results of the present study indicate that miR-193a-3p may be an EMT-related
biomarker and serve as a novel prognostic factor for CRC.
PMID- 28693275
TI - Long non-coding RNA HOXA transcript at the distal tip as a biomarker for gastric
cancer.
AB - A long non-coding RNA named HOXA transcript at the distal tip (HOTTIP) has been
reported to be significantly increased in several cancers, including
hepatocellular cancer, pancreatic cancer and lung cancer. However, the clinical
value of HOTTIP expression in gastric cancer remains unknown. The present study
aimed to investigate HOTTIP expression levels in gastric cancer and to elucidate
its clinical significance. Reverse transcription polymerase chain reaction was
used to assess the expression level of HOTTIP in gastric cancer cell lines and
tissues. In a cohort of 94 patients with gastric cancer, HOTTIP expression was
significantly lower in cancer tissues compared with the normal adjacent tissues.
In addition, receiver operating characteristic (ROC) curve analysis was performed
to evaluate the diagnostic value of HOTTIP in gastric cancer, and the area under
the ROC curve was 0.767. In conclusion, the results of the present study
indicated that HOTTIP may be a predictive biomarker for gastric cancer.
PMID- 28693276
TI - Examination of the predictive factors of the response to whole brain radiotherapy
for brain metastases from lung cancer using MRI.
AB - Previous studies have been conducted on the prognostic factors for overall
survival in patients with brain metastases (BMs) following whole brain
radiotherapy (WBRT). However, there have been a small number of studies regarding
the prognostic factors for the response of tumor to WBRT. The aim of the present
study was to identify the predictive factors for the response to WBRT from the
point of view of reduction of tumor using magnetic resonance imaging. A
retrospective analysis of 62 patients with BMs from primary lung cancer treated
with WBRT was undertaken. The effects of the following factors on the response to
WBRT were evaluated: Age; sex; performance status; lactate dehydrogenase;
pathology; existence of extracranial metastases; activity of extracranial
disease; chemo-history; chest radiotherapy history; treatment term; gamma-knife
radiotherapy; diffusion weighted image signal intensity; tumor diameter; extent
of edema and the edema/tumor (E/T) ratio. The association between the reduction
of tumors and clinical factors was evaluated using logistic regression analysis.
P<0.05 was considered to indicate a statistically significant difference. The
overall response ratio of this cohort was 54.8%. In the univariate analysis, the
response of tumors was associated with the presence of small cell lung carcinoma
(SCLC; P=0.0007), an E/T ratio of >=1.5 (P=0.048), and a median tumor diameter of
<20 mm (P=0.014). In the multivariate analysis, the presence of SCLC [P=0.001;
odds ratio (OR), 17.152), an E/T ratio of >=1.5 (P=0.019; OR, 9.526), and the
presence of extracranial metastases (P=0.031; OR, 4.875) were revealed to be
independent predictive factors for the reduction of tumor. The following 3
factors were significantly associated with the response of tumors to WBRT: The
presence of SCLC; an E/T ratio of >=1.5; and the presence of extracranial
metastases. The E/T ratio is a novel index that provides a simple and easy
predictive method for use in a clinical setting.
PMID- 28693277
TI - Curcumol triggers apoptosis of p53 mutant triple-negative human breast cancer MDA
MB 231 cells via activation of p73 and PUMA.
AB - Triple-negative breast cancer (TNBC; estrogen receptor-negative, progesterone
receptor-negative and Her-2-negative) is often accompanied by a higher frequency
of p53 gene mutations. Therefore, TNBC is challenging to treat due to a lack of
biological targets and a poor sensitivity to conventional therapies. Curcumol is
a monomer composition isolated from the ethanol extracts of Curcuma wenyujin, a
Chinese medicinal herb traditionally used as a cancer remedy. Previous studies
have revealed that curcumol is able to block proliferation in various human tumor
cell lines. However, the underlying mechanisms have yet to be elucidated. The
present study aimed to investigate the anticancer effects of curcumol in the
human p53 mutant TNBC MDA-MB-231 cell line and its underlying mechanisms. Cell
viability and growth were determined by MTT and a mice xenograft model assay,
respectively. Cell cycle distribution was examined by flow cytometry. Apoptosis
was evaluated by apoptotic morphology analysis with DAPI staining and flow
cytometric analysis following Annexin V/propidium iodide staining. The protein
expression in cells was evaluated by immunoblotting. Treatment of MDA-MB-231
cells with curcumol resulted in a significant inhibition of cell proliferation in
vitro [half maximal inhibitory concentration (IC50)=240.7+/-85.0 ug/ml for 48 h
and IC50=100.2+/-13.5 ug/ml for 72 h]. Curcumol treatment also resulted in the
suppression of xenograft growth in vivo (100 or 200 ug/kg for 21 days), as well
as G1 phase arrest and an apoptotic response, which were accompanied by the
upregulation of p73 expression and the activation of the expression of p53
upregulated modulator of apoptosis (PUMA) and Bcl-2 antagonistic killer (Bak). No
cleavage of poly (ADP-ribose) polymerase was detected. To the best of our
knowledge, the present data demonstrate for the first time that curcumol inhibits
the growth of MDA-MB-231 cells and triggers p53-independent apoptosis, which may
be mediated by the p73-PUMA/Bak signaling pathway. Curcumol may, therefore, be a
potential compound for use in the development of novel TNBC therapeutics.
PMID- 28693278
TI - Sunitinib does not impair natural killer cell function in patients with renal
cell carcinoma.
AB - Although the available treatment options have expanded, the survival of patients
with metastatic renal cell carcinoma (RCC) remains poor. As patients with RCC
lack responsiveness to chemotherapy or radiation, therapeutic options
predominantly include surgical interventions and immunomodulatory approaches,
including the administration of tyrosine kinase inhibitors (TKIs) such as
sunitinib. Natural killer (NK) cells have been reported to be key players in TKI
mediated off-target effects on the immune system. However, only limited
information is available regarding the possible impact of sunitinib on the
function of NK cells of individual patients. The present study reports on the
immunomonitoring results of three patients with metastatic RCC who underwent
sunitinib treatment. These results were compared with age-matched, healthy
controls in terms of the immune status of T, B and NK cells, focusing on
functional in vitro analyses of NK cells. In all three patients, NK cell number,
subset distribution and function, as measured by cluster of differentiation 107a
degranulation, did not exhibit any significant alterations as a result of
sunitinib treatment. These results indicate that sunitinib does not negatively
affect NK cell function, which supports the pursuit of therapeutic modalities
that combine immunomodulation and NK cell-stimulating approaches.
PMID- 28693279
TI - MicroRNA-215 acts as a tumor suppressor in breast cancer by targeting AKT
serine/threonine kinase 1.
AB - There are accumulating reports that microRNAs are dysregulated in a number of
human cancer types, and that they may function as tumor suppressors or oncogenes
in tumorigenesis and tumor development. microRNA-215 (miR-215) has been
identified as a tumor suppressor in epithelial ovarian, pancreatic, non-small
cell lung and colon cancer, whereas it may act as an oncogene in gastric and
cervical cancer. The role of miR-215 in breast cancer carcinogenesis and
progression has yet to be elucidated. In the present study, the expression level
of miR-215 was determined in breast cancer tissues and cell lines using the
reverse transcription-quantitative polymerase chain reaction. The effects of miR
215 overexpression on proliferation and the invasive capacity of breast cancer
cells were assessed using MTT and cell invasion assays. The results revealed that
miR-215 was significantly downregulated in breast cancer tissues and cell lines.
Restoration of miR-215 expression inhibited the proliferation and invasion of
breast cancer cells. The underlying molecular mechanism for the suppression of
proliferation and invasion by miR-215 was investigated. AKT serine/threonine
kinase 1 (AKT1) was validated as a novel direct target of miR-215, and the effect
of AKT1 small interfering RNA mimicked the effect of miR-215 overexpression in
breast cancer cells. These results indicated that miR-215 acted as a tumor
suppressor, and that its downregulation in tumor tissues may contribute to the
carcinogenesis and progression of breast cancer, indicating that miR-215 may be a
novel therapeutic target for the treatment of breast cancer.
PMID- 28693280
TI - Improved antitumor effect of ionizing radiation in combination with rapamycin for
treating nasopharyngeal carcinoma.
AB - The aim of the present study is to investigate if rapamycin is a radiosensitizer
of nasopharyngeal carcinoma (NPC), and to identify which pathways are involved in
radiation sensitization. In vitro, using untreated cells as the control, NPC
cells were treated with rapamycin, ionizing radiation (IR) or both. Differences
in the phosphorylation of ribosomal protein S6 and glycogen synthase kinase (GSK)
3beta, expression of cyclin D1, clonogenic survival, number of phosphorylated
histone subunit 2AX (gammaH2AX) foci, and cell cycle status between the study
groups were compared. The results indicated that rapamycin alone decreased the
phosphorylation of S6 and GSK3beta, as well as the expression of cyclin D1, in
NPC cells. Thus, rapamycin-treated NPC cells had lower cell viability, and higher
DNA damage and G1 arrest than control cells. In addition, the combination of
rapamycin and IR caused the highest cell death, DNA damage and G1 arrest when
compared with the effects caused by either treatment alone. In conclusion,
rapamycin improves the anti-tumor effect of IR for treating NPC through
inhibiting the Akt/mechanistic target of rapamycin/S6 and Akt/GSK3beta/cyclin D1
signaling pathways.
PMID- 28693281
TI - Coffee reduces KRAS expression in Caco-2 human colon carcinoma cells via
regulation of miRNAs.
AB - Previous epidemiological studies have demonstrated that moderate coffee
consumption is associated with a lower risk of certain types of cancer,
particularly colon cancer. To elucidate the molecular basis for this protective
action, the effect of coffee on Caco-2 human colon carcinoma cells was
investigated. Low concentrations of coffee (<5%) inhibited proliferation of Caco
2 cells without affecting cell viability. Coffee also reduced KRAS proto
oncogene, GTPase (KRAS) gene expression in a dose-dependent manner; however,
caffeine, caffeic acid and chlorogenic acid, three major constituents of coffee,
did not exhibit this effect. Increasing the duration of coffee bean roasting
increased the reduction in KRAS expression, suggesting that the active
constituents responsible for this effect emerged during the roasting process.
MicroRNA (miR) analysis revealed that coffee induced the expression of miR-30c
and miR-96, both of which target the KRAS gene. The results of the present study
suggested that daily coffee consumption may reduce KRAS activity, thereby
preventing the malignant growth of colon carcinoma cells.
PMID- 28693282
TI - Identification of hub genes and pathways associated with bladder cancer based on
co-expression network analysis.
AB - The aim of the present study was to identify hub genes and signaling pathways
associated with bladder cancer (BC) utilizing centrality analysis and pathway
enrichment analysis. The differentially expressed genes (DEGs) were screened from
the ArrayExpress database between normal subjects and BC patients. Co-expression
networks of BC were constructed using differentially co-expressed genes and
links, and hub genes were investigated by degree centrality analysis of co
expression networks in BC. The enriched signaling pathways were investigated by
Kyoto Encyclopedia of Genes and Genomes database analysis based on the DEGs. The
hub gene expression in BC tissues was validated using reverse transcription
quantitative polymerase chain reaction (RT-qPCR) and western blotting. A total of
329 DEGs were screened, including 147 upregulated and 182 downregulated genes.
The co-expression network constructed between BC and normal controls consisted of
182 nodes and 434 edges, and the two genes in each gene pair were differentially
co-expressed genes. Centrality analysis of co-expression networks suggested that
the top 5 hub genes with high degree included lectin, galactoside-binding,
soluble, 4 (LGALS4), protein tyrosine phosphatase, receptor type N2 (PTPRN2),
transmembrane protease, serine 11E (TMPRSS11E), tripartite motif containing 31
(TRIM31) and potassium voltage-gated channel subfamily D member 3 (KCND3).
Pathway analysis revealed that the 329 DEGs were significantly enriched in 5
terms (cell cycle, DNA replication, oocyte meiosis, p53 signaling pathway and
peroxisome proliferator-activated receptor signaling pathway). According to RT
qPCR and western blot analysis, 4/5 hub genes were significantly expressed,
including LGALS4, PTPRN2, TMPRSS11E, TRIM31; however, KCND3 was not significantly
expressed. In the present study, 5 hub genes were successfully identified
(LGALS4, PTPRN2, TMPRSS11E, TRIM31 and KCND3) and 5 biological pathways that may
be underlying biomarkers for early diagnosis and treatment associated with
bladder cancer were revealed.
PMID- 28693283
TI - Prospective exploratory study of gemcitabine and S-1 against elderly patients
with advanced non-small cell lung cancer.
AB - A prospective study was conducted to investigate the efficacy of a combined
regimen of gemcitabine and S-1 for the treatment of elderly patients (>70 years)
with advanced non-small cell lung cancer (NSCLC) as a first-line setting based on
the dosage recommended in a previous phase I study. Chemotherapy-naive patients
with advanced NSCLC received gemcitabine plus S-1. S-1 (40 mg/m2) was
administered orally twice daily for 14 days while gemcitabine (1,000 mg/m2) was
administered on days 1 and 15 of each cycle, and this regimen was repeated every
4 weeks. A total of 20 patients were included in the present study. Of these, 8
patients achieved an overall response rate of 40.0%, and the overall disease
control rate was 65.0%. According to the histological type, the response rate in
patients with NSCLC and adenocarcinoma was 38.5%, and that for non-adenocarcinoma
was 42.9%. Progression-free survival and median survival times were 6.4 months
and 17.8 months, respectively. Grade 3 or 4 hematological toxicities observed
were leukopenia (29%) and neutropenia (24%), while febrile neutropenia was not
observed in any patient. The only non-hematological adverse event observed was
grade 3 skin rash (10%). Therefore, the combination of gemcitabine and S-1 may be
a promising and feasible regimen in the first-line setting for elderly patients
with advanced NSCLC.
PMID- 28693284
TI - beta-human chorionic gonadotropin-secreting intracranial germ-cell tumor
associated with high testosterone in an adult man: A case report.
AB - A 38-year-old male patient presented with general weakness, polydipsia and a body
weight loss of 10 kg in two years. Hypopituitarism with central hypothyroidism
and central adrenal insufficiency were noted at Taipei City Hospital (Taipei,
Taiwan). However, hypogonadotropic hypergonadism was also observed. The patient
was diagnosed with an intracranial beta-human chorionic gonadotropin (beta-hCG)
secreting germ-cell tumor, and brain magnetic resonance imaging revealed that the
tumor involved the pineal gland, stalk, posterior pituitary gland, right basal
ganglion, hypothalamus, corpus callosum and posterior hippocampus. The
cerebrospinal fluid (CSF) beta-hCG level was 1936 IU/l, while the alpha
fetoprotein (AFP) level was <0.24 ng/ml. The serum AFP level of the patient was
3.28 ng/ml, and the beta-hCG level was 178 IU/l with a CSF:serum beta-hCG ratio
>2:1. The patient was successfully treated with chemotherapy and radiotherapy, as
demonstrated by a marked decrease in size of the tumor and in the serum beta-hCG
levels. Intracranial beta-hCG secreting germ-cell tumors are rare in adults and
manifest differently compared with patients of early pubertal age. In contrast
with the precocious puberty frequently observed in young patients, the diagnosis
of adult patients is often delayed and the symptoms are associated with tumor
size and location. The present case report described an adult male with an
intracranial beta-hCG secreting GCT, demonstrating hypopituitarism and
asymptomatic hyperandrogenemia, and reviews and discusses the literature relevant
to the case.
PMID- 28693285
TI - Characterization of gammadelta T cells in patients with non-small cell lung
cancer.
AB - Systemic immune defects that are associated with disease progression exist in a
variety of malignancies. gammadelta T cells are innate-like lymphocytes that do
not require self-major histocompatibility complex-restricted priming. Ex vivo
expanded circulating gammadelta T cells exhibit promising antitumor activity and
are a potential candidate for the treatment of various malignancies, including
non-small cell lung cancer (NSCLC). In the present study, flow cytometry was used
as a method to study the phenotypes and characteristics of gammadelta T cells. A
lower frequency of circulating gammadelta T cells was observed in NSCLC patients
than in healthy controls. In advanced NSCLC patients, gammadelta T cells were
also detected in the pleural effusion, but the frequency of gammadelta T cells
here was significantly lower than in the peripheral blood. Vdelta1+and Vdelta1
Vdelta2- T cells represented the most enriched subsets in the pleural effusion.
Moreover, the present study demonstrated that Vdelta1+ T cells are a type of
gammadelta T cells characterized by a cluster of differentiation (CD)3dim T-cell
receptor (TCR)gammadeltabright phenotype, whereas Vdelta2+ T cells represent a
CD3brightTCRgammadeltadim phenotype, according to the fluorescence intensity of
CD3 and gammadeltaTCR using flow cytometry. Finally, the present study reported a
decrease in the expression of CD27 and CD28 molecules on the surface of
circulating gammadelta T cells in NSCLC. The present data suggest the existence
of a dysregulated repertoire of gammadelta T cells in NSCLC, which exhibit
impaired activation and a reformed cytokine-releasing profile. Although the ex
vivo expansion of gammadelta T cells may be a prospective therapeutic strategy in
NSCLC patients, it remains necessary to clarify which subsets (Vdelta1 or
Vdelta2) should be expanded and the sources from which gammadelta T cells should
be generated.
PMID- 28693286
TI - Bevacizumab as a last-line treatment for glioblastoma following failure of
radiotherapy, temozolomide and lomustine.
AB - In previous trials, bevacizumab failed to prolong the overall survival time in
newly diagnosed glioblastoma and at the first recurrence. Randomized clinical
trials at the second or further recurrence following the failure of radiotherapy,
temozolomide and lomustine, and retrospective analyses focusing on this specific
cohort, are not yet available. A total of 62 patients with glioblastoma who
received bevacizumab after the failure of standard care, including radiotherapy,
temozolomide and lomustine, were retrospectively identified. Patient
characteristics, previous treatment details, concomitant therapy, response based
on the Response Assessment in Neuro-Oncology criteria, and progression-free
survival (PFS) and overall survival (OS) times and rates were evaluated.
Furthermore, the PFS and OS times and rates were analyzed for responders and non
responders. Of the patients, 54.8% (n=34) responded to treatment [complete
response (CR) 3.2%, n=2; partial response (PR) 51.6%, n=32]. The median PFS time
was 3.5 months and the median OS time was 7.5 months. The PFS rate at 6 months
was 21.5% and the OS rate at 12 months was 11.5%. Responders (CR or PR)
experienced a superior median PFS time compared with non-responders (i.e. stable
or progressive disease; 5.4 vs. 1.9 months; P<0.0001) and a superior PFS rate at
6 months (34.9 vs. 7.1%; P<0.0001). The median OS time (8.6 vs. 6.4 months;
P<0.0001) and OS rate at 12 months (21.3 vs. 0%; P<0.0001) were also superior in
patients who exhibited a response to bevacizumab treatment. In conclusion, the
objective response rate and the PFS and OS times and rates indicate that
bevacizumab has activity in patients with glioblastoma following the failure of
radiotherapy, temozolomide, and lomustine. A randomized trial comparing
bevacizumab with best supportive care in these patients is advised.
PMID- 28693287
TI - Effect of thymoquinone on head and neck squamous cell carcinoma cells in vitro:
Synergism with radiation.
AB - Thymoquinone (TQ) is the main bioactive constituent present in black seed oil
(Nigella sativa); it has shown anti-inflammatory and anti-neoplastic effects in
various cancer cell types. The aim of the present study was to investigate the
effects of TQ on head and neck squamous cell carcinoma (HNSCC) cell lines, on its
own and in combination with radiation and cisplatin, respectively. The SCC25 and
CAL27 HNSCC cell lines were treated with TQ alone and in combination with
cisplatin or radiation, respectively. Proliferation assays and clonogenic assays
were performed. Apoptosis was detected by flow cytometry. TQ exhibited dose
dependent cytotoxicity via apoptosis in the investigated cell lines. In
combination with cisplatin, TQ resulted in no significant increase in
cytotoxicity. Combined with radiation, TQ significantly reduced clonogenic
survival compared with each treatment method alone. TQ is a promising agent in
the treatment of head and neck cancer due to its anti-proliferative and
radiosensitizing properties. However, the combination of TQ with cisplatin showed
no therapeutic benefit in vitro.
PMID- 28693288
TI - Epigallocatechin-3-gallate inhibits growth and induces apoptosis in esophageal
cancer cells through the demethylation and reactivation of the p16 gene.
AB - The present study aimed to investigate the effect of treatment with
epigallocatechin-3-gallate (EGCG) on the human esophageal cancer cell line ECa109
and elucidate the associated underlying mechanisms. ECa109 cells were cultured
and treated with increasing concentrations of EGCG for various durations. Cell
viability was evaluated using the MTT assay and apoptosis was detected using flow
cytometry. The methylation status of the cyclin-dependent kinase inhibitor 2A
(p16) gene was analyzed using the methylation-specific polymerase chain reaction
(PCR). p16 mRNA and protein expression was measured using reverse transcription
quantitative PCR and western blot analysis, respectively. The results of the
present study demonstrated that, following treatment with EGCG, ECa109 cell
viability was significantly decreased, while the rate of apoptosis was
significantly increased (P<0.01), in a dose- and time-dependent manner. Following
treatment of ECa109 cells with EGCG, p16 gene demethylation, and its mRNA and
protein expression, were significantly increased compared with the untreated
cells (P<0.01). EGCG may induce ECa109 cell apoptosis and inhibit cell growth
through p16 gene demethylation, which restores its expression.
PMID- 28693289
TI - Antitumor effects of curcumin in human bladder cancer in vitro.
AB - Bladder cancer is one of the major causes of cancer-associated mortality, with a
high incidence. Curcumin, a polyphenol compound extracted from turmeric, has been
identified to regulate tumor progression. However, the therapeutic effect of
curcumin in human bladder cancer has not yet been determined. In the present
study, the effects of curcumin on cell growth, apoptosis and migration of bladder
cancer cell lines were evaluated using an MTT assay, a Transwell assay and flow
cytometry, and the associated mechanisms were investigated using western blot
analysis. Curcumin was identified to decrease the growth of T24 and 5637 cells in
a dose- and time-dependent manner. The present study confirmed that curcumin is
able to inhibit cell migration and promote apoptosis of bladder cancer through
suppression of matrix metalloproteinase signaling pathways in vitro. The
anticancer effects of curcumin on bladder cancer cells may benefit clinical
practice in the future.
PMID- 28693290
TI - Therapy with transcutaneous administration of imiquimod combined with oral
administration of sorafenib suppresses renal cell carcinoma growing in an
orthotopic mouse model.
AB - Imiquimod is an imidazoquinoline immune response modifier that is used in
antiviral and antiallergic creams. Combination therapy using transcutaneous
imiquimod and oral sorafenib was previously demonstrated to reduce the tumor
burden of renal cell carcinoma growing cutaneously in a mouse model. In the
present study, an orthotopic mouse model was used to investigate whether combined
treatment with oral sorafenib and transcutaneous imiquimod inhibited renal cell
carcinoma growing in the kidney. Kidneys of female BALB/c mice were
orthotopically implanted with RENCA mouse kidney cancer cells, and the mice were
transcutaneously treated with cream containing imiquimod and/or with orally
administered sorafenib 5 days following cell implantation. Tumor burden and
incidence were determined 28 days following the start of therapy. Splenocyte
activity was quantified using the 51Cr release assay and the fluorescence
activated cell sorting assay with cluster of differentiation (CD) 4 and CD8
antibodies. Imiquimod, sorafenib and combination therapy were tolerated well. A
combination of transcutaneous imiquimod and oral sorafenib inhibited the growth
of RENCA tumors in the kidney significantly compared with the control. The 51Cr
release assay demonstrated that transcutaneous imiquimod therapy significantly
induced the release of 51Cr from RENCA cells compared with the control. The
fluorescence-activated cell sorting assay demonstrated that transcutaneous
imiquimod therapy induced CD8+ and CD4- splenocytes compared with the control. In
summary, the results of the present study demonstrated that combined treatment
with transcutaneous imiquimod and oral sorafenib may be a promising strategy for
the treatment of patients with renal cell carcinoma.
PMID- 28693291
TI - Diagnostic clue of nodular fasciitis mimicking metastasis in papillary thyroid
cancer, mismatching findings on 18F-FDG PET/CT and 123I whole body scan: A case
report.
AB - This study reports a case of nodular fasciitis incidentally detected in a patient
with papillary thyroid cancer. A 47-year-old woman underwent a total
thyroidectomy and radioactive iodine therapy for papillary thyroid cancer. On a
follow-up fluorodeoxyglucose (18F-FDG) PET/computed tomography (CT) scan after 12
months, a focal 18F-FDG-avid lesion was incidentally detected in the paraspinal
muscle. It was well-enhanced on CT and magnetic resonance imaging, indicating
metastasis. However, the lesion was not iodine avid on the 123I whole body scan,
which favored benign etiology over metastasis from thyroid cancer. For
pathological confirmation, surgical excision was performed and the paraspinal
lesion was finally confirmed as nodular fasciitis. Therefore, it was suggested
that nodular fasciitis may be included in the differential diagnosis of a 18F-FDG
avid/iodine non-avid soft tissue lesion in patients with thyroid cancer. In such
circumstances, 123I whole body scans may serve a role in non-invasive work-up,
and prevent unnecessary surgical procedures.
PMID- 28693292
TI - Computed tomography and magnetic resonance imaging features of ovarian
fibrothecoma.
AB - The aim of the present study was to investigate the imaging characteristics of
ovarian fibrothecoma. The cases of 25 female patients with pathologically
confirmed ovarian fibrothecomas were retrospectively reviewed. Tumor location,
size, density, signal intensity, cystic degeneration, calcification, enhancement
pattern and ascites were assessed by computed tomography (CT) (n=20) and magnetic
resonance imaging (MRI) (n=5). Clinical and histological features were also
evaluated. The results revealed that 23 (92.0%) patients were postmenopausal,
with a mean age +/- standard deviation (SD) of 60.7+/-10.8 years old. All 25
tumors were unilateral and a thickened endometrium was observed in 7 (28.0%)
patients. In total, 24 (96.0%) tumors appeared to have well-defined boundaries,
with 1 (4%) tumor exhibiting an obscure boundary. Tumors had a mean size of 9.8+/
5.3 cm. Solid and predominantly solid masses were found in 16 cases (64.0%), and
cystic and predominantly cystic masses were found in 9 patients (36.0%). Solid
regions of masses exhibited hypodensity or isodensity in 24 patients (96.0%),
with 1 patient (4.0%) exhibiting hyperdensity. The mean CT value (+/- SD) was
44.2+/-12.8 HU (range, 31-79HU) in unenhanced images. All masses exhibited
isointensity or slight hypointensity on T1-weighted imaging, and tumor parenchyma
also exhibited slight hypointensity or isointensity on T2-weighted imaging
compared with the myometrium, with or without areas of patchy hyperintensity.
Contrast-enhanced CT or MRI scans were performed on 19 patients, and the solid
components (94.7%) exhibited mild to moderate enhancement in 18 patients and 1
patient (5.3%) exhibited intense enhancement. Tumor size was positively
correlated with the tumor cystic degeneration (r=0.77, P<0.001) and ascites
(r=0.41, P<0.001). Therefore, ovarian fibrothecoma typically presents as solid or
predominant solid masses with clear boundaries; the parenchyma of the tumor
exhibits isodensity on CT scans, slight hypointensity or isointensity on MRI and
mild enhancement following contrast-medium injection. The thickened endometrium
observed in postmenopausal woman may also be a valuable imaging feature.
PMID- 28693293
TI - MAPK inhibitors enhance cell death in pyrogallol-treated human pulmonary
fibroblast cells via increasing O2*- levels.
AB - Pyrogallol (PG) induces apoptosis in lung cancer cells via the overproduction of
O2*- and affects mitogen-activated protein kinases (MAPKs) in these cells. The
aim of the present study was to elucidate the effect of PG and/or MAPK inhibitors
on human pulmonary fibroblast (HPF) cell viability in relation to reactive oxygen
species (ROS) and glutathione (GSH). Treatment with 50 or 100 uM PG inhibited the
viability of HPF cells, and induced cell death and the loss of mitochondrial
membrane potential (MMP; DeltaPsim). In particular, treatment with 100 uM PG
induced cell death via apoptosis as well as necrosis in HPF cells. PG increased
mitochondrial O2*- levels and the number of GSH-depleted HPF cells. All the MAPK
(mitogen-activated protein kinase kinase, c-Jun N-terminal kinase and p38)
inhibitors enhanced the inhibition of cell viability, cell death and MMP
(DeltaPsim) loss in 100 uM PG-treated HPF cells. All the inhibitors increased the
O2*- levels in 100 uM PG-treated HPF cells, but none of the inhibitors
significantly altered the PG-induced GSH depletion. In conclusion, PG treatment
induced cell death via apoptosis and necrosis in HPF cells. Treatment with MAPK
inhibitors slightly enhanced cell death in PG-treated HPF cells. HPF cell death
induced by PG and/or MAPK inhibitors was at least partially associated with
changes in O2*- levels and GSH content. The present data provided useful
information to understand PG-induced normal lung cell death in association with
MAPK signaling pathways and ROS levels.
PMID- 28693294
TI - Upregulated expression of MMP-9 in gingival epithelial cells induced by prolonged
stimulation with arecoline.
AB - Betel quid chewing is implicated in the high prevalence of oral cancer in
Southeast Asian countries. One of the major components of betel quid is
arecoline. In the present study, in order to characterize the association between
chronic arecoline stimulation and carcinogenesis the expression level of matrix
metalloproteinase (MMP)-2, MMP-9, tissue inhibitor of metalloproteinase (TIMP)-1
and TIMP-2 mRNA in human gingival epithelial progenitor cells (HGEPs) stimulated
with arecoline was assessed. The HGEPs were alternated between 3 days of
incubation with arecoline (50 ug/ml), and 3 days without arecoline, for up to 30
days. The expression levels of the MMPs and TIMPs in the cells stimulated with
arecoline were evaluated by reverse transcription-quantitative polymerase chain
reaction at 18 and 30 days. The expression of MMP-9 mRNA in the experimental
group was significantly increased compared with in the control group (P<0.01). No
significant differences in the expression of MMP-2, TIMP-1 or TIMP-2 mRNA were
observed between the experimental and control groups. Using an MMP-9 activity
assay, the levels of MMP-9 activity in the experimental group were demonstrated
to be significantly higher than in the control group (P<0.05). To investigate
associated cellular signaling pathways, PDTC [a nuclear factor (NF)
kappaB/inhibitor of NF-kappaB (IkappaB) inhibitor], PD98059 [a mitogen-activated
protein kinase kinase (MAPKK)1 and MAPKK2 inhibitor], SB203580 (a p38 MAPK
inhibitor) and 5,15-DPP [a signal transduction and activator of transcription
(STAT) 3 inhibitor] were used. All inhibitors decreased the extent of MMP-9
upregulation induced by stimulation with arecoline. Based on the data, it is
hypothesized that MMP-9 activity may be involved in the pathological alterations
of oral epithelium induced by betel quid chewing, and that the NF-kappaB/IkappaB,
MAPK, p38 MAPK and STAT3 signaling pathways may be involved in the production of
MMP-9 induced by betel quid chewing.
PMID- 28693295
TI - Germline DNA copy number variations as potential prognostic markers for non
muscle invasive bladder cancer progression.
AB - Accumulating evidence has suggested that germline DNA copy number variations
(CNVs) affect various disorders, including human malignancies. However, the
significance of CNVs in non-muscle invasive bladder cancer (NMIBC) remains
unclear. The purpose of the present study was to identify the role of CNVs in
NMIBC. Array comparative genomic hybridization (CGH) analysis was performed to
search for candidate CNVs associated with NMIBC susceptibility. Quantitative
polymerase chain reaction was carried out to evaluate CNVs associated with
patient outcome in 189 NMIBC cases. In total, 11 CNVs were associated with NMIBC
risk in array CGH analysis. Out of the 189 CNVs examined, family with sequence
similarity 81 member A (FAM81A) and proprotein convertase subtilisin/kexin type 6
(PCSK6) CNVs exhibited a significant association with recurrence and disease
progression in NMIBC. PCSK6 has been reported to regulate proliferation and tumor
progression in breast and prostate malignancies. Notably, patients with pT1 stage
had significantly lower PCSK6 relative copy number than those with pTa
(P=0.0196). In multivariate analyses, PCSK6 copy number was an independent
prognostic factor for progression-free survival (P=0.0456; risk ratio, 2.17; 95%
confidence interval, 1.02-4.82). These data suggest that PCSK6 CNV is a potential
new tumor marker for estimating disease progression in NMIBC.
PMID- 28693296
TI - Mineralized deposits in the uterus of a pig without pregnancy loss.
AB - Herein, we describe a case of uterine calcification in the uterus of a pig
without pregnancy loss. The recipient underwent cloned embryo transfer and
Cesarean section for safe delivery of cloned piglets. During the Cesarean
section, 4 white, star-like, (2 * 2 * 2) cm, calcified structures were found
within the endometrial cavity. Despite dystrophic calcification around the
placenta, healthy cloned piglets were produced successfully. To our knowledge,
this is the first reported case of dystrophic calcification occurring within the
uterus in a pregnant pig.
PMID- 28693297
TI - Evaluation of a fixed-dose combination of benazepril and pimobendan in dogs with
congestive heart failure: a randomized non-inferiority clinical trial.
AB - A fixed-dose combination tablet of benazepril and pimobendan (Fortekor Plus;
Elanco Animal Health) was tested in dogs with congestive heart failure (CHF)
caused by myxomatous mitral valve disease (MMVD) in a three-arm, masked,
randomized, non-inferiority clinical trial in Japan. The test group (n = 34)
received Fortekor Plus twice daily. Two control groups received registered
formulations of benazepril (Fortekor; Elanco Animal Health) and pimobendan
(Vetmedin; Boehringer Ingelheim Vetmedica) with administration of Vetmedin twice
daily and Fortekor twice (Control I, n = 14) or once (Control II, n = 19) daily.
Diuretics were used in 22 dogs (32.8%). Global clinical scores decreased
significantly from baseline in all groups; there were no significant differences
between groups, and non-inferiority of Fortekor Plus compared to Control I,
Control II, and combined Control I + II groups was demonstrated. There were no
significant differences between groups for relevant clinical chemistry and
hematology variables or frequency of all adverse events. Frequency of emesis was
significantly (p = 0.0042) lower in the Fortekor Plus (8.8%) group than in the
Control I + II (39.4%) group. In conclusion, Fortekor Plus had non-inferior
efficacy and was associated with significantly less emesis compared to Fortekor
and Vetmedin in dogs with CHF caused by MMVD.
PMID- 28693298
TI - Chicken RNA-binding protein T-cell internal antigen-1 contributes to stress
granule formation in chicken cells and tissues.
AB - T-cell internal antigen-1 (TIA-1) has roles in regulating alternative pre-mRNA
splicing, mRNA translation, and stress granule (SG) formation in human cells. As
an evolutionarily conserved response to environmental stress, SGs have been
reported in various species. However, SG formation in chicken cells and the role
of chicken TIA-1 (cTIA-1) in SG assembly has not been elucidated. In the present
study, we cloned cTIA-1 and showed that it facilitates the assembly of canonical
SGs in both human and chicken cells. Overexpression of the chicken prion-related
domain (cPRD) of cTIA-1 that bore an N-terminal green fluorescent protein (GFP)
tag (pntGFP-cPRD) or Flag tag (pFlag-cPRD) induced the production of typical SGs.
However, C-terminal GFP-tagged cPRD induced notably large cytoplasmic granules
that were devoid of endogenous G3BP1 and remained stable when exposed to
cycloheximide, indicating that these were not typical SGs, and that the pntGFP
tag influences cPRD localization. Finally, endogenous cTIA-1 was recruited to SGs
in chicken cells and tissues under environmental stress. Taken together, our
study provide evidence that cTIA-1 has a role in canonical SG formation in
chicken cells and tissues. Our results also indicate that cPRD is necessary for
SG aggregation.
PMID- 28693299
TI - Magnetic resonance imaging characteristics of ischemic brain infarction over time
in a canine stroke model.
AB - This study describes magnetic resonance imaging (MRI) results and changes in
lateral ventricular size over time in a canine ischemic stroke model. T1- and T2
weighted (T1W, T2W) imaging and fluid-attenuated inversion recovery (FLAIR)
sequence MRI were performed at 3 h and 3, 8, and 35 days after brain infarct
induction. Diffusion-weighted imaging (DWI) and apparent diffusion coefficient
(ADC) mapping were performed at 8 and 35 days. A total of 29 brain lesions were
induced successfully in 12 of 14 beagle dogs. At 3 h, T2W and FLAIR detected
hyperintense lesions in three randomly selected dogs. On T1W, all lesions
appeared hypointense to isointense at 3 h, isointense (18/29) or hypointense
(11/29) at 3 days, hypointense to isointense with peripheral hyperintensity
(24/26) at 8 days, and hypointense (18/26) at 35 days. Infarcts on DWI/ADC were
hypointense to isointense centrally, with the periphery hyperintense/hyperintense
(17/26) at 8 days and hypointense/hyperintense (19/26) at 35 days. A marked
increase in lateral ventricular size was observed in dogs with cerebral infarcts.
In conclusion, T2W and FLAIR were useful for detecting early stage (3 h to 3
days) brain infarction. T1W and DWI were useful for detecting neuronal necrosis
and providing supplemental information for phase evaluation.
PMID- 28693300
TI - Investigation of bovine tuberculosis outbreaks by using a trace-back system and
molecular typing in Korean Hanwoo beef cattle.
AB - Bovine tuberculosis is a chronic contagious disease responsible for major
agricultural economic losses. Abattoir monitoring and trace-back systems are an
appropriate method to control bovine tuberculosis, particularly in beef cattle.
In the present study, a trace-back system was applied to bovine tuberculosis
cases in Korean native Hanwoo beef cattle. Bovine tuberculosis was detected in
three index beef cattle during abattoir monitoring in Jeonbuk Province, Korea,
and the original herds were traced back from each index cow. All cattle in each
original herd were subjected to tuberculin skin test. The positive rates in the
tuberculin skin test were 64.6% (62 of 96), 4.8% (2 of 42), and 8.1% (3 of 37) at
farms A, B, and C, respectively. On post-mortem examination of 56 tuberculin
positive cattle, 62% had granulomatous lesions, and Mycobacterium bovis was
cultured from 40 (71.4%) of the cattle. Molecular typing by spoligotyping and the
mycobacterial interspersed repetitive unit-variable-number tandem repeat assay
revealed the genotype of the M. bovis strains from the index cattle were same as
the M. bovis genotype in each original herd. The results suggest that tracing
back from index cattle to the original herd is an effective method to control
bovine tuberculosis in beef cattle.
PMID- 28693301
TI - Serological and molecular epidemiology of Japanese encephalitis virus infections
in swine herds in China, 2006-2012.
AB - Japanese encephalitis virus (JEV) is a mosquito-borne, zoonotic flavivirus
causing viral encephalitis in humans and reproductive disorder in swine. JEV is
prevalent throughout China in human; however, spatiotemporal analysis of JEV in
Chinese swine herds has not been reported previously. Herein, we present
serological and molecular epidemiological results and estimates of prevalence of
JEV infections among swine herds in various regions of China. The results suggest
that JEV infections are widespread and genotype I and III strains co-exist in the
same regions. Therefore, there is an urgent need to monitor JEV infection status
among swine herds in China.
PMID- 28693302
TI - Packaging of Rift Valley fever virus pseudoviruses and establishment of a
neutralization assay method.
AB - Rift Valley fever (RVF) is an acute, febrile zoonotic disease that is caused by
the RVF virus (RVFV). RVF is mainly prevalent on the Arabian Peninsula, the
African continent, and several islands in the Indian Ocean near southeast Africa.
RVFV has been classified by the World Organisation for Animal Health (OIE) as a
category A pathogen. To avoid biological safety concerns associated with use of
the pathogen in RVFV neutralization assays, the present study investigated and
established an RVFV pseudovirus-based neutralization assay. This study used the
human immunodeficiency virus (HIV) lentiviral packaging system and RVFV
structural proteins to successfully construct RVFV pseudoviruses. Electron
microscopy observation and western blotting indicated that the size, structure,
and shape of the packaged pseudoviruses were notably similar to those of HIV
lentiviral vectors. Infection inhibition assay results showed that an antibody
against RVFV inhibited the infective ability of the RVFV pseudoviruses, and an
antibody neutralization assay for RVFV detection was then established. This study
has successfully established a neutralization assay based on RVFV pseudoviruses
and demonstrated that this method can be used to effectively evaluate antibody
neutralization.
PMID- 28693303
TI - A new recombined porcine reproductive and respiratory syndrome virus virulent
strain in China.
AB - Porcine reproductive and respiratory syndrome (PRRS) is one of the most important
swine diseases worldwide. In the present study, a new virulent strain of PRRS
virus (PRRSV), GDsg, was isolated in Guangdong province, China, and caused high
fever, high morbidity, and high mortality in sows and piglets. The genome of this
new strain was 15,413 nucleotides (nt) long, and comparative analysis revealed
that GDsg shared 82.4% to 94% identity with type 2 PRRSV strains, but only 61.5%
identity with type 1 PRRSV Lelystad virus strain. Phylogenetic analysis indicated
that type 2 PRRSV isolates include five subgenotypes (I, II, III, IV, and V),
which are represented by NADC30, VR-2332, GM2, CH-1a, and HuN4, respectively.
Moreover, GDsg belongs to a newly emerging type 2 PRRSV subgenotype III. More
interestingly, the newly isolated GDsg strain has multiple discontinuous nt
deletions, 131 (19 + 18 + 94) at position 1404-1540 and a 107 nt insertion in the
NSP2 region. Most importantly, the GDsg strain was identified as a virus
recombined between low pathogenic field strain QYYZ and vaccine strain JXA1-P80.
In conclusion, a new independent subgenotype and recombinant PRRSV strain has
emerged in China and could be a new threat to the swine industry of China.
PMID- 28693304
TI - Prepubertal growth and single nucleotide polymorphism analysis of the growth
hormone gene of low birth weight Holstein calves.
AB - Holstein calves weighing less than 20 kg at birth have been noted in Korea. Due
to insufficient information, we raised small calves with age-matched normal birth
weight Holstein calves and determined body weights before puberty. In addition, 3
single nucleotide polymorphisms (SNPs) of the growth hormone (GH) gene were
analyzed. Up to 10 months of age, low birth weight calves were smaller than
normal weight calves. In exon 5 of the GH gene, SNP genotype variation was
detected in some small calves; however, this did not appear to be the only factor
inducing low birth weight and slow growth.
PMID- 28693305
TI - Comparison of the characteristics of canine adipose tissue-derived mesenchymal
stem cells extracted from different sites and at different passage numbers.
AB - Mesenchymal stem cells (MSCs) have desirable characteristics for use in therapy
in animal models and veterinary medicine, due to their capacity of inducing
tissue regeneration and immunomodulation. The objective of this study was to
evaluate the differences between canine adipose tissue-derived MSCs (AD-MSCs)
extracted from subcutaneous (Sc) and visceral (Vs) sites. Surface antigenic
markers, in vitro differentiation, and mineralized matrix quantification of AD
MSCs at different passages (P4, P6, and P8) were studied. Immunophenotypic
analysis showed that AD-MSCs from both sites were CD44+, CD90+, and CD45-.
Moreover, they were able, in vitro, to differentiate into fat, cartilage, and
bone. Sc-AD-MSCs preserve in vitro multipotentiality up to P8, but Vs-AD-MSCs
only tri-differentiated up to P4. In addition, compared to Vs-AD-MSCs, Sc-AD-MSCs
had greater capacity for in vitro mineralized matrix synthesis. In conclusion, Sc
AD-MSCs have advantages over Vs-AD-MSCs, as Sc AD-MSCs preserve multipotentiality
during a greater number of passages, have more osteogenic potential, and require
less invasive extraction.
PMID- 28693306
TI - Tannic acid-mediated immune activation attenuates Brucella abortus infection in
mice.
AB - Brucellosis is an emerging infectious disease affecting humans and animals. In
this study, we investigated the in vitro and in vivo effects of tannic acid (TA)
against Brucella abortus infection. After infection, F-actin polymerization and
mitogen-activated protein kinases (MAPKs) (ERK 1/2 and p38alpha) phosphorylation
were reduced in TA-treated cells compared with that in control cells. The mice
were infected via an intraperitoneal route and were orally given TA or phosphate
buffered saline for 14 days. Spleen weights of the TA-treated and control mice
were not different; however, splenic proliferation of B. abortus was
significantly reduced in the TA-treated group. Immune response analysis showed
that, compared with the control group, non-infected TA-treated mice displayed
increased levels of interferon-gamma (IFN-gamma), monocyte chemoattractant
protein-1 (MCP-1), and interleukin-10 at 3 days post-infection and a further
increase in IFN-gamma and MCP-1 at 14 days post-infection. In contrast, compared
with the control group, infected TA-treated mice displayed elevated levels of IFN
gamma at 3 days post-infection, which continued to increase at 14 days post
infection, as was also observed for tumor necrosis factor. Taken together, the
results showing TA activation of cytokine production and inhibition of bacterial
proliferation in the host highlight a potential use of TA treatment in the
control of Brucella infection.
PMID- 28693307
TI - Polymorphism in the serotonin transporter protein gene in Maltese dogs with
degenerative mitral valve disease.
AB - Degenerative mitral valve disease (DMVD) is the most commonly acquired cardiac
disease in dogs. This study evaluated the relationship between genetic variations
in the serotonin transporter (SERT) gene of Maltese dogs and DMVD. Genomic DNA
was extracted from blood samples collected from 20 client-owned DMVD Maltese dogs
and 10 healthy control dogs, and each exon of the SERT gene was amplified via
polymerase chain reaction. The resulting genetic sequences were aligned and
analyzed for variations by comparing with reference sequences; the predicted
secondary structures of these variations were modeled and cross-verified by
applying computational methods. Genetic variations, including five nonsynonymous
genetic variations, were detected in five exons. Protein structure and function
of the five nonsynonymous genetic variations were predicted. Three of the five
polymorphisms were predicted to be probable causes of damage to protein function
and confirmed by protein structure model verification. This study identified six
polymorphisms of the SERT gene in Maltese dogs with DMVD, suggesting an
association between the SERT gene and canine DMVD. This is the first study of
SERT mutation in Maltese dogs with DMVD and is considered a pilot study into
clinical genetic examination for early DMVD diagnosis.
PMID- 28693308
TI - Isolation and characterization of a new porcine epidemic diarrhea virus variant
that occurred in Korea in 2014.
AB - Outbreaks of porcine epidemic diarrhea (PED) have resulted in significant
economic losses in the swine industry, and another PED outbreak occurred in 2014
in Korea. Isolating and culturing PED virus (PEDV) allow investigations into its
pathogenesis and the development of vaccines and diagnostic assays. In this
study, we successfully isolated two PEDV isolates (QIAP1401 and QIAP1402) from
naturally infected piglets at Jeju-do, Korea. Viral propagation was confirmed in
Vero cells based on cytopathic effect, immunofluorescence assay, reverse
transcription-polymerase chain reaction, and electron microscopic analyses. The
QIAP401 isolate propagated well in Vero cells for 70 passages, with titers of
106.5 to 107.0 50% tissue culture infectious dose/mL, which increased gradually
with passaging. The nucleotide and amino acid sequences of the QIAP1401 isolate
were determined and compared with those of other PEDV isolates. The QIAP1401
isolate was determined to be closely related to the USA/Minnesota271/2014 strain
(> 99.9% nucleotide similarity) that was isolated in the USA in 2014.
Phylogenetic analysis based on several PEDV genes suggested that a new PEDV
variant is circulating in the Korean swine industry, with 93.08% similarity to
the SM98 strain isolated in 1998. In addition, the QIAP1401 strain showed strong
virulence in 3-day-old piglets and 11-week-old growing pigs.
PMID- 28693309
TI - Variation of canine vertebral bone architecture in computed tomography.
AB - Focal vertebral bone density changes were assessed in vertebral computed
tomography (CT) images obtained from clinically healthy dogs without diseases
that affect bone density. The number, location, and density of lesions were
determined. A total of 429 vertebral CT images from 20 dogs were reviewed, and 99
focal vertebral changes were identified in 14 dogs. Focal vertebral bone density
changes were mainly found in thoracic vertebrae (29.6%) as hyperattenuating
(86.9%) lesions. All focal vertebral changes were observed at the vertebral body,
except for a single hyperattenuating change in one thoracic transverse process.
Among the hyperattenuating changes, multifocal changes (53.5%) were more common
than single changes (46.5%). Most of the hypoattenuating changes were single
(92.3%). Eight dogs, 40% of the 20 dogs in the study and 61.6% of the 13 dogs
showing focal vertebral changes in the thoracic vertebra, had hyperattenuating
changes at the 7th or 8th thoracic vertebra. Our results indicate that focal
changes in vertebral bone density are commonly identified on vertebral CT images
in healthy dogs, and these changes should be taken into consideration on
interpretation of CT images.
PMID- 28693310
TI - Tibial dyschondroplasia is closely related to suppression of expression of
hypoxia-inducible factors 1alpha, 2alpha, and 3alpha in chickens.
AB - Tibial dyschondroplasia (TD) cases has not been reported in Tibetan chickens
(TBCs), but it is commonly seen in commercial broilers characterized by lameness.
The underlying mechanism remains unclear. Hypoxia-inducible factors (HIFs) are
important regulators of cellular adaptation to hypoxic conditions. In this study,
we investigated the role of HIF-1alpha, -2alpha, and -3alpha in hypoxia and
thiram-induced TD and their effect on tibial growth plate development in Arbor
Acres chickens (AACs) and TBCs. RNA and protein expression levels of HIF-1alpha,
2alpha, and -3alpha were determined by using quantitative reverse transcriptase
polymerase chain reaction and western blotting analyses, respectively.
Interestingly, the results showed that HIF-1alpha, -2alpha, and -3alpha
expressions in the tibial growth plate of TBCs were upregulated by hypoxia and
the change was more significant in TBCs than in AACs. However, these factors were
downregulated in thiram-induced TD. To further clarify the effect of thiram on
tibial growth plate in commercial broilers, AACs were observed to exhibit more
pronounced changes in their growth plate that that in TBCs. Taken together, these
results demonstrate that HIF-1alpha, -2alpha, and -3alpha may be important in
tibial growth plate development and in the prevention of TD. The present study
contributes novel insights on a therapeutic target for poultry TD.
PMID- 28693311
TI - Piglet colibacillosis diagnosis based on multiplex polymerase chain reaction and
immunohistochemistry of paraffin-embedded tissues.
AB - Enterotoxigenic Escherichia coli (ETEC) causes diarrhea in pigs, referred to as
colibacillosis. The aim of this study was to optimize multiplex polymerase chain
reaction (PCR) and immunohistochemistry (IHC) analyses of paraffin-embedded
material to detect pathogenic E. coli strains causing colibacillosis in pigs.
Multiplex PCR was optimized for fimbriae (F18, F4, F6, F5, and F41) and toxins
(types A and B heat-stable toxins [STaP and STb], heat-labile toxin [LT], and
type 2 Shiga toxin [STx2e]), and IHC was optimized for an anti-E. coli polyclonal
antibody. Samples (132) from pigs received between 2006 and 2014 with clinical
and histopathological diagnoses of colibacillosis were analyzed. E. coli was
detected by IHC in 78.7%, and at least one virulence factor gene was detected in
71.2%. Pathogenic strains of ETEC with at least one fimbria and one toxin were
detected in 40% of the samples in multiplex PCR. The most frequent virulence
types were F18-STaP (7.5%), F18-STaP-STb (5.7%), and F4-STaP (3.8%). A
statistically significant association was noted between virulence factors F4,
F18, STaP, and STb and positive immunostaining results. Colibacillosis diagnosis
through multiplex PCR and IHC of paraffin-embedded tissues is a practical
approach, as samples can be fixed and stored for long periods before analysis.
PMID- 28693312
TI - In vitro treatment of lipopolysaccharide increases invasion of Pasteurella
multocida serotype B:2 into bovine aortic endothelial cells.
AB - Pasteurella multocida serotype B:2 causes hemorrhagic septicemia in cattle and
buffalo. The invasion mechanism of the bacterium when invading the bloodstream is
unclear. This study aimed to characterize the effects of immunomodulatory
molecules, namely dexamethasone and lipopolysaccharide, on the invasion
efficiency of P. multocida serotype B:2 toward bovine aortic endothelial cells
(BAECs) and the involvement of actin microfilaments in the invasion mechanism.
The results imply that treatment of BAECs with lipopolysaccharide at 100 ng/mL
for 24 h significantly increases the intracellular bacteria number per cell (p <
0.01) compared with those in untreated and dexamethasone-treated cells. The
lipopolysaccharide-treated cells showed a significant decrease in F-actin
expression and an increase in G-actin expression (p < 0.001), indicating actin
depolymerization of BAECs. However, no significant differences were detected in
the invasion efficiency and actin filament reorganization between the
dexamethasone-treated and untreated cells. Transmission electron microscopy
showed that P. multocida B:2 resided in a vacuolar compartment of dexamethasone
treated and untreated cells, whereas the bacteria resided in cellular membrane of
lipopolysaccharide-treated cells. The results suggest that lipopolysaccharide
destabilizes the actin filaments of BAECs, which could facilitate the invasion of
P. multocida B:2 into BAECs.
PMID- 28693313
TI - Comparative proteomic analysis of outer membrane protein 43 (omp43)-deficient
Bartonella henselae.
AB - Outer membrane proteins (OMPs) of Gram-negative bacteria constitute the first
line of defense protecting cells against environmental stresses including
chemical, biophysical, and biological attacks. Although the 43-kDa OMP (OMP43) is
major porin protein among Bartonella henselae-derived OMPs, its function remains
unreported. In this study, OMP43-deficient mutant B. henselae (Deltaomp43) was
generated to investigate OMP43 function. Interestingly, Deltaomp43 exhibited
weaker proliferative ability than that of wild-type (WT) B. henselae. To study
the differences in proteomic expression between WT and Deltaomp43, two
dimensional gel electrophoresis-based proteomic analysis was performed. Based on
Clusters of Orthologus Groups functional assignments, 12 proteins were associated
with metabolism, 7 proteins associated with information storage and processing,
and 3 proteins associated with cellular processing and signaling. By semi
quantitative reverse transcriptase polymerase chain reaction, increases in tldD,
efp, ntrX, pdhA, purB, and ATPA mRNA expression and decreases in Rho and yfeA
mRNA expression were confirmed in Deltaomp43. In conclusion, this is the first
report showing that a loss of OMP43 expression in B. henselae leads to retarded
proliferation. Furthermore, our proteomic data provide useful information for the
further investigation of mechanisms related to the growth of B. henselae.
PMID- 28693314
TI - Plasmonic Vertically Coupled Complementary Antennas for Dual-Mode Infrared
Molecule Sensing.
AB - Here we report an infrared plasmonic nanosensor for label-free, sensitive,
specific, and quantitative identification of nanometer-sized molecules. The
device design is based on vertically coupled complementary antennas (VCCAs) with
densely patterned hot-spots. The elevated metallic nanobars and complementary
nanoslits in the substrate strongly couple at vertical nanogaps between them,
resulting in dual-mode sensing dependent on the light polarization parallel or
perpendicular to the nanobars. We demonstrate experimentally that a monolayer of
octadecanethiol (ODT) molecules (thickness 2.5 nm) leads to significant antenna
resonance wavelength shift over 136 nm in the parallel mode, corresponding to 7.5
nm for each carbon atom in the molecular chain or 54 nm for each nanometer in
analyte thickness. Additionally, all four characteristic vibrational fingerprint
signals, including the weak CH3 modes, are clearly delineated experimentally in
both sensing modes. Such a dual-mode sensing with a broad wavelength design range
(2.5 to 4.5 MUm) is potentially useful for multianalyte detection. Additionally,
we create a mathematical algorithm to design gold nanoparticles on VCCA sensors
in simulation with their morphologies statistically identical to those in
experiments and systematically investigate the impact of the nanoparticle
morphology on the nanosensor performance. The nanoparticles form dense hot-spots,
promote molecular adsorption, enhance near-field intensity 103 to 104 times, and
improve ODT refractometric and fingerprint sensitivities. Our VCCA sensor
structure offers a great design flexibility, dual-mode operation, and high
detection sensitivity, making it feasible for broad applications from biomarker
detection to environment monitoring and energy harvesting.
PMID- 28693315
TI - Interlaced CNT Electrodes for Bacterial Fouling Reduction of Microfiltration
Membranes.
AB - Interlaced carbon nanotube electrodes (ICE) were prepared by vacuum filtering a
well-dispersed carbon nanotube-Nafion solution through a laser-cut acrylic
stencil onto a commercial polyvinylidene fluoride (PVDF) microfiltration (MF)
membrane. Dead-end filtration was carried out using 107 and 108 CFU mL-1
Pseudomonas fluorescens to study the effects of the electrochemically active ICE
on bacterial density and morphology, as well as to evaluate the bacterial fouling
trend and backwash (BW) efficacy, respectively. Finally, a simplified COMSOL
model of the ICE electric field was used to help elucidate the antifouling
mechanism in solution. At 2 V DC and AC (total cell potential), the average
bacterial log removal of the ICE-PVDF increased by ~1 log compared to the control
PVDF (3.5-4 log). Bacterial surface density was affected by the presence and
polarity of DC electric potential, being 87-90% lower on the ICE cathode and 59
93% lower on the ICE anode than that on the PVDF after filtration, and BW further
reduced the density on the cathode significantly. The optimal operating
conditions (2 V AC) reduced the fouling rate by 75% versus the control and
achieved up to 96% fouling resistance recovery (FRR) during BW at 8 V AC using
155 mM NaCl. The antifouling performance should mainly be due to electrokinetic
effects, and the electric field simulation by COMSOL model suggested
electrophoresis and dielectrophoresis as likely mechanisms.
PMID- 28693317
TI - Osmotic Heat Engine Using Thermally Responsive Ionic Liquids.
AB - The osmotic heat engine (OHE) is a promising technology for converting low grade
heat to electricity. Most of the existing studies have focused on thermolytic
salt systems. Herein, for the first time, we proposed to use thermally responsive
ionic liquids (TRIL) that have either an upper critical solution temperature
(UCST) or lower critical solution temperature (LCST) type of phase behavior as
novel thermolytic osmotic agents. Closed-loop TRIL-OHEs were designed based on
these unique phase behaviors to convert low grade heat to work or electricity.
Experimental studies using two UCST-type TRILs, protonated betaine
bis(trifluoromethyl sulfonyl)imide ([Hbet][Tf2N]) and choline
bis(trifluoromethylsulfonyl)imide ([choline][Tf2N]) showed that (1) the specific
energy of the TRIL-OHE system could reach as high as 4.0 times that of the
seawater and river water system, (2) the power density measured from a commercial
FO membrane reached up to 2.3 W/m2, and (3) the overall energy efficiency reached
up to 2.6% or 18% of the Carnot efficiency at no heat recovery and up to 10.5% or
71% of the Carnet efficiency at 70% heat recovery. All of these results clearly
demonstrated the great potential of using TRILs as novel osmotic agents to design
high efficient OHEs for recovery of low grade thermal energy to work or
electricity.
PMID- 28693316
TI - Rapid Dissolution of ZnO Nanoparticles Induced by Biological Buffers
Significantly Impacts Cytotoxicity.
AB - Zinc oxide nanoparticles (nZnO) are one of the most highly produced nanomaterials
and are used in numerous applications including cosmetics and sunscreens despite
reports demonstrating their cytotoxicity. Dissolution is viewed as one of the
main sources of nanoparticle (NP) toxicity; however, dissolution studies can be
time-intensive to perform and complicated by issues such as particle separation
from solution. Our work attempts to overcome some of these challenges by
utilizing new methods using UV/vis and fluorescence spectroscopy to
quantitatively assess nZnO dissolution in various biologically relevant
solutions. All biological buffers tested induce rapid dissolution of nZnO. These
buffers, including HEPES, MOPS, and PIPES, are commonly used in cell culture
media, cellular imaging solutions, and to maintain physiological pH. Additional
studies using X-ray diffraction, FT-IR, X-ray photoelectron spectroscopy, ICP-MS,
and TEM were performed to understand how the inclusion of these nonessential
media components impacts the behavior of nZnO in RPMI media. From these
assessments, we demonstrate that HEPES causes increased dissolution kinetics,
boosts the conversion of nZnO into zinc phosphate/carbonate, and, interestingly,
alters the structural morphology of the complex precipitates formed with nZnO in
cell culture conditions. Cell viability experiments demonstrated that the
inclusion of these buffers significantly decrease the viability of Jurkat
leukemic cells when challenged with nZnO. This work demonstrates that
biologically relevant buffering systems dramatically impact the dynamics of nZnO
including dissolution kinetics, morphology, complex precipitate formation, and
toxicity profiles.
PMID- 28693318
TI - Ammonia Electrosynthesis with High Selectivity under Ambient Conditions via a Li+
Incorporation Strategy.
AB - We report the discovery of a dramatically enhanced N2 electroreduction reaction
(NRR) selectivity under ambient conditions via the Li+ incorporation into poly(N
ethyl-benzene-1,2,4,5-tetracarboxylic diimide) (PEBCD) as a catalyst. The
detailed electrochemical evaluation and density functional theory calculations
showed that Li+ association with the O atoms in the PEBCD matrix can retard the
HER process and can facilitate the adsorption of N2 to afford a high potential
scope for the NRR process to proceed in the "[O-Li+].N2-Hx" alternating
hydrogenation mode. This atomic-scale incorporation strategy provides new insight
into the rational design of NRR catalysts with higher selectivity.
PMID- 28693319
TI - Controlled Generation of Quantized Vortex-Antivortex Pairs in a Superconducting
Condensate.
AB - Quantized vortices, as topological defects, play an important role in both
physics and technological applications of superconductors. Normally, the
nucleation of vortices requires the presence of a high magnetic field or current
density, which allow the vortices to enter from the sample boundaries. At the
same time, the controllable generation of individual vortices inside a
superconductor is still challenging. Here, we report the controllable creation of
single quantum vortices and antivortices at any desirable position inside a
superconductor. We exploit the local heating effect of a scanning tunneling
microscope (STM) tip: superconductivity is locally suppressed by the tip and
vortex-antivortex pairs are generated when supercurrent flows around the hot
spot. The experimental results are well-explained by theoretical simulations
within the Ginzburg-Landau approach.
PMID- 28693320
TI - Performance and Mechanisms of Ultrafiltration Membrane Fouling Mitigation by
Coupling Coagulation and Applied Electric Field in a Novel Electrocoagulation
Membrane Reactor.
AB - A novel electrocoagulation membrane reactor (ECMR) was developed, in which
ultrafiltration (UF) membrane modules are placed between electrodes to improve
effluent water quality and reduce membrane fouling. Experiments with feedwater
containing clays (kaolinite) and natural organic matter (humic acid) revealed
that the combined effect of coagulation and electric field mitigated membrane
fouling in the ECMR, resulting in higher water flux than the conventional
combination of electrocoagulation and UF in separate units (EC-UF). Higher
current densities and weakly acidic pH in the EMCR favored faster generation of
large flocs and effectively reduced membrane pore blocking. The hydraulic
resistance of the formed cake layers on the membrane surface in ECMR was reduced
due to an increase in cake layer porosity and polarity, induced by both
coagulation and the applied electric field. The formation of a polarized cake
layer was controlled by the applied current density and voltage, with cake layers
formed under higher electric field strengths showing higher porosity and
hydrophilicity. Compared to EC-UF, ECMR has a smaller footprint and could achieve
significant energy savings due to improved fouling resistance and a more compact
reactor design.
PMID- 28693321
TI - d Orbital Topological Insulator and Semimetal in the Antifluorite Cu2S Family:
Contrasting Spin Helicities, Nodal Box, and Hybrid Surface States.
AB - We reveal a class of three-dimensional d orbital topological materials in the
antifluorite Cu2S family. Derived from the unique properties of low-energy t2g
states, their phases are solely determined by the sign of the spin-orbit coupling
(SOC): topological insulator (TI) for negative SOC and topological semimetal for
positive SOC, both having Dirac cone surface states but with contrasting
helicities. With broken inversion symmetry, the semimetal becomes one with a
nodal box consisting of butterfly-shaped nodal lines that are robust against SOC.
Further breaking the tetrahedral symmetry by strain leads to an ideal Weyl
semimetal with four pairs of Weyl points. Interestingly, the Fermi arcs coexist
with a surface Dirac cone on the (010) surface, as required by a [Formula: see
text] invariant.
PMID- 28693322
TI - Nanopore Sensing of Protein Folding.
AB - Single-molecule studies of protein folding hold keys to unveiling protein folding
pathways and elusive intermediate folding states-attractive pharmaceutical
targets. Although conventional single-molecule approaches can detect folding
intermediates, they presently lack throughput and require elaborate labeling.
Here, we theoretically show that measurements of ionic current through a nanopore
containing a protein can report on the protein's folding state. Our all-atom
molecular dynamics (MD) simulations show that the unfolding of a protein lowers
the nanopore ionic current, an effect that originates from the reduction of ion
mobility in proximity to a protein. Using a theoretical model, we show that the
average change in ionic current produced by a folding-unfolding transition is
detectable despite the orientational and conformational heterogeneity of the
folded and unfolded states. By analyzing millisecond-long all-atom MD simulations
of multiple protein transitions, we show that a nanopore ionic current recording
can detect folding-unfolding transitions in real time and report on the structure
of folding intermediates.
PMID- 28693323
TI - Supramolecular Host-Guest Interaction-Enhanced Adjustable Drug Release Based on
beta-Cyclodextrin-Functionalized Thermoresponsive Porous Polymer Films.
AB - Drug delivery systems based on stimuli-responsive porous polymer films (PPFs)
have been extensively investigated because of their many advantages. However, the
ability to adjust the drug release from PPFs is not always perfect, and at times,
it cannot satisfy real-world requirements. In this paper, supramolecular host
guest interactions were harnessed to overcome the difficulties associated with
adjustable release from these systems by incorporating host molecules into the
pore walls of thermoresponsive PPFs. beta-Cyclodextrin-functionalized porous
amphiphilic block copolymer films (beta-CD-PBCPFs) with controllable pore
parameters, high homogeneity, and large areas were prepared by combining the self
assembly and breath-figure methods. Drug-loaded beta-CD-PBCPFs displayed
thermoresponsive release behavior, which could be tuned by increasing the beta-CD
content in phosphate-buffered saline. The release was governed by the host-guest
interactions of the beta-CD moieties and drug molecules. The concept of host
guest interaction-enhanced adjustable release could be applied to different drug
molecules, such as doxorubicin and metronidazole.
PMID- 28693324
TI - ZnO Nanoparticle Fortified Highly Permeable Carbon/Silica Monoliths as a Flow
Through Media.
AB - We demonstrate a facile one-pot synthesis of porous "flow-through" ZnO
nanoparticle impregnated carbon/silica monoliths with high mechanical strength
and interconnected end-to-end pores decorated with functional and catalytic
nanoparticles. The materials and conditions for the synthesis were tailored to
achieve the desired properties of high mechanical strength, good flow-through
permeability, and crack-free morphology. Monoliths were prepared from a
resorcinol formaldehyde rout but with the addition of tetraethyl-orthosilicate
and a metal oxide precursor, ZnCl2. The monoliths were ambient dried and
carbonized under optimized conditions to suppress cracks. Compressive tests of
both the resin and carbonized monoliths were performed to examine the effect of
the metal oxide precursor on the mechanical properties. The permeability of the
monoliths was determined to verify their utility as a flow-through material. The
monoliths exhibited a high compressive modulus of ~30 MPa compared with
conventional carbon aerogels and a permeability of ~10-12 m2. Various
characterization techniques were used to analyze the surface morphology, pore
texture, and chemical composition of the monoliths. Finally, Ag nanoparticles
were incorporated in the monoliths to demonstrate an example of a "flow-through"
catalysis application where controlled catalytic conversion of para-nitrophenol
into para-aminophenol could be achieved in a continuous flow reactor mode.
PMID- 28693325
TI - Transparent Silk Fibroin Microspheres from Controlled Droplet Dissolution in a
Binary Solution.
AB - Silk is a natural polymer with a broad range of potential applications in
textiles, advanced materials, biomedical devices, and drug delivery. The ability
to control the morphology and assembly of silk fibroin is essential for the
fabrication of silk-based structured materials. Here, we report an effective and
simple approach based on droplet dissolution for weaving silk fibroin into
spheres of several hundred micrometers in diameter. The spheres possess regular
wrinkled microstructures on the surface and switchable transparency for visible
light. To produce these silk spheres, we immersed a sessile microdrop of the silk
fibroin aqueous solution in a surrounding phase of ethanol in toluene at low
concentration (<10%). The droplet experienced a two-phase process: the first
phase of volume expansion due to the intake of organic solvents from the
surrounding phase and the second phase of droplet dissolution. The dissolution
rate is closely related to the dynamics of the droplet, while the resulting
microstructure of the silk microsphere is simply adjusted by the composition of
the surrounding solution. At high concentrations of ethanol, silk fibroin formed
a thin shell around the droplet during the initial expansion of the droplet in
volume. As the droplet shrank at a later stage, the shell around the droplet
wrinkled and crumpled, leading to regular ridges and crevices on the microsphere
surface. This work demonstrates that controlled droplet dissolution may be
explored as a novel and effective way to tailor microstructures of silk
assemblies. The as-prepared silk microspheres may be potentially used as optical
units or microcarriers.
PMID- 28693326
TI - Multiscale Morphology of Nanoporous Copper Made from Intermetallic Phases.
AB - Many application-relevant properties of nanoporous metals critically depend on
their multiscale architecture. For example, the intrinsically high step-edge
density of curved surfaces at the nanoscale provides highly reactive sites for
catalysis, whereas the macroscale pore and grain morphology determines the
macroscopic properties, such as mass transport, electrical conductivity, or
mechanical properties. In this work, we systematically study the effects of alloy
composition and dealloying conditions on the multiscale morphology of nanoporous
copper (np-Cu) made from various commercial Zn-Cu precursor alloys. Using a
combination of X-ray diffraction, electron backscatter diffraction, and focused
ion beam cross-sectional analysis, our results reveal that the macroscopic grain
structure of the starting alloy surprisingly survives the dealloying process,
despite a change in crystal structure from body-centered cubic (Zn-Cu starting
alloy) to face-centered cubic (Cu). The nanoscale structure can be controlled by
the acid used for dealloying with HCl leading to a larger and more faceted
ligament morphology compared to that of H3PO4. Anhydrous ethanol dehydrogenation
was used as a probe reaction to test the effect of the nanoscale ligament
morphology on the apparent activation energy of the reaction.
PMID- 28693327
TI - In situ examination of osteoblast biomineralization on sulfonated polystyrene
modified substrates using Fourier transform infrared microspectroscopy.
AB - Osteoporosis is a skeletal disorder that is characterized by the loss of bone
mineral density (BMD) resulting in increased risk of fracture. However, it has
been shown that BMD is not the only indicator of fracture risk, as the strength
of bone depends on a number of factors, including bone mass, architecture and
material properties. Physiological mineral deposition requires the formation of a
properly developed extracellular matrix (ECM), which recruits calcium and
phosphate ions into the synthesis of apatite crystals. Temporal and spatial
compositional and structural changes of biological apatite greatly depend on the
properties of the crystals initially formed. As such, Fourier-transform infrared
microspectroscopy (FTIRM) is capable of examining adaptive remodeling by
providing compositional information such as the level of mineralization and
carbonate substitution, as well as quality and perfection of the mineral phase.
The objective of this study was to evaluate the in vitro mineralization
development of MC3T3-E1 murine calvarial preosteoblasts cultured on different
substrata by comparing FTIRM measurements from two subclones (mineralizing
subclone 4 and nonmineralizing subclone 24) maintained in culture for up to 21
days. The results showed that modulation of the substrate surface using a thin
coating of sulfonated polystyrene (SPS) provided favorable conditions for the
development of a mineralizable ECM and that the mineral formed by the osteoblasts
was similar to that of fully mineralized bone tissue. Specifically, the
mineralizing subclone produced significantly more mineral phosphate when cultured
on SPS-coated substrates for 21 days, compared to the same culture on bare
substrates. In contrast, the level of mineralization in nonmineralizing subclone
was low on both SPS-coated and uncoated substrates. The mineralizing subclone
also produced comparable amounts of collagen on both substrates; however,
mineralization was significantly higher in the SPS culture. The nonmineralizing
subclone produced comparable amounts of collagen on day 1 but much less on day
21. Collagen maturity ratio increased in the mineralizing subclone from day 1 to
day 21, but remained unchanged in the nonmineralizing subclone. These results
suggest that SPS-treatment of the substrate surface may alter collagen
remodeling; however, other factors may also influence osteoblast mineralization
in the long term.
PMID- 28693328
TI - Eliminating Disparities in Asthma Care: Identifying Broad Challenges in Quality
Improvement.
AB - Racial disparities in asthma care persist in New York State's Medicaid Program.
African Americans with asthma experience higher rates of emergency department
visits and inpatient hospitalizations, coupled with lower rates of long-term
control medication use compared to other racial/ethnic groups. Within this
context, and with funding from the Centers for Disease Control and Prevention,
the New York State Department of Health designed and implemented the Eliminating
Disparities in Asthma Care (EDAC) Collaborative to improve the quality of asthma
care delivered in 7 provider sites located in Central Brooklyn, New York. EDAC
was a partnership of the New York State Medicaid and Asthma Control Programs, 6
New York City-based managed care plans, and community-based health care
providers. Over the 5-year funding period, improvements in documented asthma
severity diagnosis and control classification were observed. This article
describes the EDAC approach, successes, and challenges.
PMID- 28693329
TI - A Novel Approach to Improving Patient Experience in Orthopedics.
AB - The patient experience domain comprises a significant portion of the Hospital
Value-Based Purchasing program. This study investigated whether an intervention
focusing on attending physician awareness, resident and physician assistant
education, and multidisciplinary patient-centric care had an effect on patient
perceived physician communication and overall hospital ratings. Responses to the
Hospital Consumer Assessment of Healthcare Providers and Systems survey were
reviewed in 2014 and 2015. Patients' perceptions that the physician explained
their condition in ways they understood and the overall hospital rating improved
significantly after implantation of the model ( P < .05). Patient-physician
communication is important for high-quality health care and is becoming
increasingly more important in hospital economics. These methods may serve as a
protocol for other institutions to improve the patient experience.
PMID- 28693330
TI - Reducing Unnecessary Blood Chemistry Testing in the Emergency Department:
Implementation of Choosing Wisely.
AB - Point of care (POC) laboratory testing is used to improve emergency department
(ED) throughput but often overuses resources by duplicating formal laboratory
testing. This study sought to evaluate the effect of a multimodal intervention on
duplicate chemistry testing. This pre-post analysis included all visits to 2
urban EDs between June 2014 and June 2016. The multimodal intervention including
provider education, signage, electronic health record redesign, and audit and
feedback focused on reducing duplicate chemistry testing. The primary outcome was
the number of duplicate chemistry tests per 100 visits. Autoregressive integrated
moving-average models were used to account for secular changes. A total of 299
701 ED visits were included. The daily number of duplicate chemistry and POC
chemistry tests significantly decreased following the intervention (3.3 fewer
duplicates and 10.2 fewer POC per 100 ED visits, P < .0001). This implementation
of a multimodal quality improvement intervention yielded substantial reductions
in the overuse of blood chemistry testing in the ED.
PMID- 28693331
TI - Patient and Provider Characteristics Associated With Optimal Post-Fracture
Osteoporosis Management.
AB - Despite an estimated 2 million osteoporosis (OP)-related fractures annually,
quality of care for post-fracture OP management remains low. This study aimed to
identify patient and provider characteristics associated with achieving or not
achieving optimal post-fracture OP management, as defined by the current HEDIS
quality measure. The study included women 67 to 85 years of age, with >=1
fracture, and continuous enrollment in a Humana insurance plan. The study
identified a higher percentage of black women in the not achieved group (6.2% vs
5.4%; P < .0001) and Hispanic women in the achieved group (3.0% vs 1.3%; P <
.0001). The not achieved group largely included patients residing in the South
and urban and suburban areas. The majority of providers were primary care or OP
related specialty, and 66% did not achieve the 4-star OP rating. The study
findings can guide development of predictive models to identify at-risk women to
improve post-fracture OP management.
PMID- 28693332
TI - Correlations Among Hospital Quality Measures: What "Hospital Compare" Data Tell
Us.
AB - A number of quality rating systems to rank health care providers have been
developed over the years with the intention of helping consumers make informed
health care purchasing decisions. Many use sets of individual quality measures to
calculate a global rating. The utility of a global rating for consumer choice
hinges on the relationships among included measures and the extent to which they
jointly reflect an underlying dimension of quality. Publicly reported data on 4
quality domains-complication, mortality, readmission, and patient safety-from
Centers for Medicare & Medicaid Services' Hospital Compare website were used to
examine correlations among individual measures within each measure group (within
group correlations) and correlations between pairs of measures across different
measure groups (between-group correlations). Modest within-group correlations
were found in only 2 domains (mortality and readmission), and there were no
meaningful between-group associations. These findings raise questions about
whether consumers can reliably depend on global quality ratings to make informed
decisions.
PMID- 28693333
TI - Complication Rates, Hospital Size, and Bias in the CMS Hospital-Acquired
Condition Reduction Program.
AB - In 2016, Medicare's Hospital-Acquired Condition Reduction Program (HAC-RP) will
reduce hospital payments by $364 million. Although observers have questioned the
validity of certain HAC-RP measures, less attention has been paid to the
determination of low-performing hospitals (bottom quartile) and the assignment of
penalties. This study investigated possible bias in the HAC-RP by simulating
hospitals' likelihood of being in the worst-performing quartile for 8 patient
safety measures, assuming identical expected complication rates across hospitals.
Simulated likelihood of being a poor performer varied with hospital size. This
relationship depended on the measure's complication rate. For 3 of 8 measures
examined, the equal-quality simulation identified poor performers similarly to
empirical data (c-statistic approximately 0.7 or higher) and explained most of
the variation in empirical performance by size (Efron's R2 > 0.85). The Centers
for Medicare & Medicaid Services could address potential bias in the HAC-RP by
stratifying by hospital size or using a broader "all-harm" measure.
PMID- 28693334
TI - Impact of Hospital-Wide Comprehensive Pain Management Initiatives.
AB - This project aimed to improve pain management through clinician education,
updated assessment tools, computer resources, and improved ordering and delivery
systems. Clinicians were surveyed and results analyzed using Wilcoxon-Mann
Whitney testing and chi2 testing. Prescribing patterns were evaluated by
comparing proportions of prescription orders and dose intervals. Cochran-Armitage
Trend Test was used for linear trends in proportion of prescription orders over
time. Knowledge scores improved significantly for nurses ( P = .004) and nurse
practitioners/physician assistants ( P < .0001). Patient surveys showed a
reduction in the percentage of patients dissatisfied with pain control. There was
a decrease of 3.6% in intramuscular orders of opioids ( P < .0001). A significant
reduction was found in the percentage of orders of potentially high initial doses
of opioids of hydromorphone and morphine after implementing an electronic alert.
This project demonstrates that a comprehensive educational strategy with improved
assessment tools, clinical resources, and educational programming can have a
significant impact on pain management.
PMID- 28693335
TI - Reputation and the Best Hospital Rankings: What Does It Really Mean?
AB - U.S. News & World Report's annual Best Hospital Rankings are determined by an
index of quality based on objective and subjective measures. This study
investigates relationships between U.S. News score and its individual subjective
and objective components that ultimately determine the relative ranking of the
top 50 hospitals in the 2015 Best Hospital Rankings for the study's selected
specialties-cancer, cardiology, gastroenterology, neurology, and orthopedics. A 2
step linear regression model was employed; first, to control for objective
components' influence on U.S. News score ( R2 = 0.365; P < .001), then, to
isolate the subjective component of reputation's effect on U.S. News score ( R2 =
0.565; P < .001). The second model confirmed that reputation has a more
significant influence on total U.S. News score than its objective counterparts.
This indicates that a hospital's U.S. News score and relative ranking in the Best
Hospital Rankings may be disproportionately influenced by its reputation.
PMID- 28693336
TI - Quick Sequential [Sepsis-Related] Organ Failure Assessment (qSOFA) and St. John
Sepsis Surveillance Agent to Detect Patients at Risk of Sepsis: An Observational
Cohort Study.
AB - The 2016 Sepsis-3 guidelines included the Quick Sequential [Sepsis-related] Organ
Failure Assessment (qSOFA) tool to identify patients at risk of sepsis. The
objective was to compare the utility of qSOFA to the St. John Sepsis Surveillance
Agent among patients with suspected infection. The primary outcomes were in
hospital mortality or admission to the intensive care unit. A multiple center
observational cohort study design was used. The study population comprised 17 044
hospitalized patients between January and March 2016. For the primary analysis,
receiver operator characteristic curves were constructed for patient outcomes
using qSOFA and the St. John Sepsis Surveillance Agent, and the areas under the
curve were compared against a baseline risk model. Time-to-event clinical process
modeling also was applied. The St. John Sepsis Surveillance Agent, when compared
to qSOFA, activated earlier and was more accurate in predicting patient outcomes;
in this regard, qSOFA fell far behind on both objectives.
PMID- 28693337
TI - Systems Opportunities to Reduce ED Crowding From Nonemergency Referrals.
AB - Emergency department (ED) crowding threatens patient safety and is associated
with increased mortality. This study explored the role of nonurgent referrals to
the ED in crowding and collaborated on a large quality initiative with the study
institution's accountable care organization (ACO) to provide timely alternatives
to such referrals. Fifty-two percent of nonemergent ED patients report contacting
a medical provider prior to coming to the ED, with 70% of those providers
directing the patient to go to the ED. Fifty-nine percent of patients indicated
that they would have accepted a clinic appointment in lieu of going to the ED.
The authors collaborated on a multidisciplinary ED alternatives quality
improvement effort with leadership to address these nonemergent referrals. ED
visits per 1000 ACO patients declined significantly following survey results and
ACO implementation of increased alternative ambulatory resources.
PMID- 28693338
TI - In vitro antiplasmodial and cytotoxic activities of sesquiterpene lactones from
Vernonia fimbrillifera Less. (Asteraceae).
AB - Due to the in vitro antiplasmodial activity of leaf extracts from Vernonia
fimbrillifera Less. (Asteraceae), a bioactivity-guided fractionation was carried
out. Three sesquiterpene lactones were isolated, namely 8-(4'
hydroxymethacrylate)-dehydromelitensin (1), onopordopicrin (2) and 8alpha-[4'
hydroxymethacryloyloxy]-4-epi-sonchucarpolide (3). Their structures were
elucidated by spectroscopic methods (1D and 2D NMR and MS analyses) and by
comparison with published data. The isolated compounds exhibited antiplasmodial
activity with IC50 values <= 5 MUg/mL. Cytotoxicity of the compounds against a
human cancer cell line (HeLa) and a mouse lung epithelial cell line (MLE12) was
assessed to determine selectivity. Compound 3 displayed promising selective
antiplasmodial activity (SI > 10).
PMID- 28693339
TI - Changes in Body Mass Index During a 3-Year Elementary School-Based Obesity
Prevention Program for American Indian and White Rural Students.
AB - BACKGROUND: Childhood obesity is a significant but largely modifiable health
risk, disproportionately affecting socioeconomically disadvantaged, racial/ethnic
minority, and rural children. Elementary school-aged children typically
experience the greatest increases in excess weight gain and therefore are
important targets for reducing adolescent and adult obesity while improving
children's health. Our study evaluated outcomes of a 3-year elementary school
based program for reducing obesity in American Indian and White students
attending eight rural schools in the U.S. upper Midwest. METHOD: Researchers
measured body mass indexes (BMI) and other health indicators and behaviors of 308
beginning third-grade students and then again at the end of students' third,
fourth, and fifth grades. The primary focus of this study is a mixed multilevel
longitudinal model testing changes in age- and gender-adjusted BMI z scores (
zBMI). RESULTS: There was a significant decrease in zBMI across the 3-year study
period. Ethnicity analyses showed that White students had overall decreases in
zBMI whereas American Indian students' zBMIs remained stable across the program.
Comparisons with children from an age- and cohort-matched national sample
provided support for the effectiveness of the school program in reducing BMI and
obesity during the study period. CONCLUSION: An elementary school-based health
program that addresses a range of students' obesity-related health behaviors, the
school health environment, and that involves educators and parents is an
effective intervention for reducing or stabilizing BMI in rural White and
American Indian students. School health programs for students living in rural
communities may be especially effective due to greater school and community
cohesiveness, and valuing of the school's primary role in improving community
health.
PMID- 28693340
TI - Quality of Care and Its Impact on One-Year Mortality: The Georgia Coverdell Acute
Stroke Registry.
AB - Although performance measures help monitor the process change in quality
improvement, their utility in measuring long-term outcomes is uncertain. This
study assessed the 1-year mortality of acute ischemic stroke patients treated by
hospitals participating in the Georgia Coverdell Acute Stroke Registry. Using 10
nationally approved performance measures, quality of care was defined both as an
all-or-none measure (defect-free care) and as a composite index. A generalized
estimating equation was applied to assess the effect of quality of care on 1-year
mortality. Defect-free care did not serve the purpose; however, the composite
measure showed that patients who received the lowest and intermediate quality
care, respectively, had a 3.94 (95% confidence interval: 3.27, 4.75; P < .0001)
and a 1.38 (95% confidence interval: 1.12, 1.62; P = .002) times higher odds of
dying in 1 year compared to those who got the best-quality stroke care.
Therefore, hospitals should be encouraged to implement quality improvement
activities for better long-term patient outcome.
PMID- 28693341
TI - Effect of exercise intensity on Nrf2 signalling in young men.
AB - INTRODUCTION: The transcription factor Nrf2 is the master regulator of
antioxidant defence. Recent data indicate a single bout of moderate-intensity
stationary cycling at a constant workload upregulates Nrf2 signalling in young,
but not older men; however, the role of exercise intensity on Nrf2 activation has
not been tested. We hypothesised that a high-intensity interval session would
elicit a greater Nrf2 response than moderate aerobic exercise. METHODS: Nrf2
signalling in response to two 30-min cycling protocols (high-intensity interval
and constant workload) was compared in young men (25 +/- 1y, n = 16).
Participants completed exercise trials in random order with blood collected pre-,
immediately post-, and 30-mins post exercise. Five participants completed a
control trial without any physical activity. Nrf2 signalling was determined by
measuring protein expression of Nrf2 in whole cell and nuclear fractions. Plasma
8-isoprostanes as well as peripheral mononuclear cell glutathione reductase (GR)
and superoxide dismutase activity were measured as markers of oxidative stress.
RESULTS: The exercise trials elicited significant increases in nuclear Nrf2 (p <
.01), but increases in whole cell Nrf2 did not reach statistical significance. GR
activity and plasma 8-isoprostanes increased significantly in response to
exercise (p < .05), and GR response was higher in the high-intensity trial (p <
.05). CONCLUSION: Our findings indicate that acute aerobic exercise elicits
activation of nuclear Nrf2, regardless of exercise intensity, but that higher
intensity exercise results in greater activity of GR. Future experiments should
explore the effect of exercise mode and duration on Nrf2 signalling, and the role
of intensity in compromised populations.
PMID- 28693342
TI - Integrated Quality Health Care System Practice in Health Care Establishments: An
Empirical Study.
PMID- 28693343
TI - The potential role of endothelial dysfunction and platelet activation in the
development of thrombotic risk in COPD patients.
AB - INTRODUCTION: Despite lack of knowledge in the field, several studies have
underlined the role of endothelium dysfunction and platelet activation as
significant players in the development and progression of chronic obstructive
pulmonary disease (COPD). Indeed, endothelium plays a crucial role in vascular
homeostasis and impairment, due to the inflammation process enhanced by smoking.
Chronic inflammation and endothelial dysfunction have been proved to drive
platelet activity. Consequently, thrombotic risk is enhanced in COPD, and might
explain the higher percentage of cardiovascular death in such patients. Areas
covered: This review aims to clarify the role of endothelium function and
platelet hyper-activity as the pathophysiological mechanisms of the increased
thrombotic risk in COPD. Expert commentary: In COPD patients, chronic
inflammation does not impact only on lung parenchyma, but potentially involves
all systems, including the endothelium of blood vessels. Impaired endothelium has
several consequences, such as reduced vasodilatation capacity, enhanced blood
coagulation, and increased platelet activation resulting in higher risk of
thrombosis in COPD patients. Endothelium dysfunction and platelet activation are
potential targets of therapy in patients with COPD aiming to reduce their risk of
cardiovascular events.
PMID- 28693344
TI - Ultrasound-mediated drug delivery by gas bubbles generated from a chemical
reaction.
AB - Highly echogenic and ultrasound-responsive microbubbles such as nitrogen and
perfluorocarbons have been exploited as ultrasound-mediated drug carriers. Here,
we propose an innovative method for drug delivery using microbubbles generated
from a chemical reaction. In a novel drug delivery system, luminol encapsulated
in folate-conjugated bovine serum albumin nanoparticles (Fol-BSAN) can generate
nitrogen gas (N2) by chemical reaction when it reacts with hydrogen peroxide
(H2O2), one of reactive oxygen species (ROS). ROS plays an important role in the
initiation and progression of cancer and elevated ROS have been observed in
cancer cells both in vitro and in vivo. High-intensity focussed ultrasound (HIFU)
is used to burst the N2 microbubbles, causing site-specific delivery of
anticancer drugs such as methotrexate. In this research, the drug delivery system
was optimised by using water-soluble luminol and Mobil Composition of Matter-41
(MCM-41), a mesoporous material, so that the delivery system was sensitive to
micromolar concentrations of H2O2. HIFU increased the drug release from Fol-BSAN
by 52.9 +/- 2.9% in 10 minutes. The cytotoxicity of methotrexate was enhanced
when methotrexate is delivered to MDA-MB-231, a metastatic human breast cancer
cell line, using Fol-BSAN with HIFU. We anticipate numerous applications of
chemically generated microbubbles for ultrasound-mediated drug delivery.
PMID- 28693345
TI - Anesthesia Quality and Patient Safety in China: A Survey.
AB - : There has been no nationwide investigation into anesthesia quality and patient
safety in China. The authors surveyed Chinese anesthesiologists about anesthesia
quality by sending a survey to all anesthesiologist members of the New Youth
Anesthesia Forum via WeChat. The respondents could choose to use a mobile device
or desktop to complete the survey. The overall response rate was 43%.
Intraoperative monitoring: 77.9% of respondents reported that electrocardiogram
monitoring was routinely applied for all patients; only 55% of the respondents
reported that they routinely used end-tidal carbon dioxide monitoring for their
patients under general anesthesia. OUTCOME MEASUREMENTS: 10.3% of respondents
admitted that they had at least one wrong medicine administration in the past 3
months; 12.4% reported that they had at least one case of cardiac arrest in the
past year. This is the first anesthesia quality survey in China. The findings
revealed potential anesthesia safety issues in China.
PMID- 28693346
TI - Cytomegalovirus (CMV) infection and pregnancy-potential for improvements in
Australasian maternity health providers' knowledge.
AB - PURPOSE: To assess the knowledge, practice and attitudes of maternity clinicians
regarding congenital cytomegalovirus (CMV). It is the most common congenital
infection, and well-recognized cause of neurodevelopmental disability and hearing
loss. New consensus recommendations state all pregnant women and health-care
providers should be educated about congenital CMV infection and preventive
measures. MATERIALS AND METHODS: An email questionnaire was distributed in
October 2015 to specialists, diplomates (general practitioners), and trainees of
the Royal Australian New Zealand College of Obstetricians and Gynaecologists
(RANZCOG), and Victorian and New South Wales midwives. RESULTS: 774 responded:
(37.3% specialists, 17.3% diplomates, 16.8% trainees, 28.6% midwives). Clinicians
had variable knowledge of fetal sequelae, transmission routes and prevention.
Overall, 30.2% felt confident about discussing CMV in pregnancy: less than 10% of
midwives (7.4%) and less than half of specialists (47.1%, p < .0001). Only 8.8%
of respondents routinely discussed CMV prevention with pregnant women. The
majority (69.3%) responded that professional societies should make practice
recommendations, and 88% thought more patient information was needed, preferably
leaflets. CONCLUSIONS: Australasian maternity clinicians lack confidence and
knowledge about congenital CMV. Few (<10%) routinely provide advice on
prevention. There is urgent need for clinical guidance and patient information to
reduce the burden of disease.
PMID- 28693347
TI - Improving Physician Communication With Patients as Measured by HCAHPS Using a
Standardized Communication Model.
AB - Physicians often fail to communicate well with patients. The objective of this
retrospective controlled interrupted time series study was to evaluate the impact
of a standardized communication intervention to improve physician communication.
All patients ages 18 years or older (N = 7739 visits) admitted to University of
Utah Health Care in Salt Lake City, Utah, from July 1, 2012, to June 31, 2014,
were included. Obstetrics, rehabilitation, and psychiatric patients were
excluded. The primary outcome was the percentage of patients who answered
"Always" to all HCAHPS questions regarding physician-patient communication. Among
the intervention group, the primary outcome increased from 56% to 63% ( P = .014,
N = 1021) while remaining stable for the control group (65% to 66%, P = .6, N =
6718). The downward trend reversed after the intervention (-0.6% to +1.7% per
month, P < .001). Standardized communication was associated with improvement in
physician communication HCAHPS scores.
PMID- 28693348
TI - CALM Interventions: Behavioral Health Crisis Assessment, Linkage, and Management
Improve Patient Care.
AB - Emergency departments (EDs) have seen rising numbers of patients in psychiatric
crises, patient boarding, and throughput delays. This study describes and
evaluates the impact of a Crisis Assessment Linkage and Management (CALM) service
designed to manage behavioral health crises. A year-to-year comparison was
performed before (n = 2211 ED visits) and after implementation of CALM (n =
2387). CALM was associated with reductions in median ED and hospital length of
stay (LOS) from 9.5 to 7.3 hours and 46.2 to 31.4 hours, respectively. Mean
transformed ED LOS decreased by 32.4% ( P < .001). The CALM model improved
patient care and throughput metrics by proactively managing behavioral health
crises.
PMID- 28693349
TI - The wounded maternity in the fine arts.
AB - The historian Fielding Garrison wrote that the history of medicine is the history
of mankind, as it encompasses all of human life. This means that the history of
medicine encourages us to critically reflect not only on the information (the
what, the world of facts) but also invites us to move towards understanding (the
who, the world of stories). Next to the historical change, there is the
anthropological duration with its baggage of immutable values that art brings to
light. The merit of art is to focus not only on the biological aspects, but also
on the social and emotional ones that define the mother/child relationship. The
paintings that we have analyzed "speak" of care and caregiving, grief and
suffering where maternity is experienced in solitude, in misery, in sickness. And
it is to this latter aspect that we have drawn our attention. Most of the works
are autobiographical or relate to events actually experienced by the artist. The
theme of the wounded maternity has many facets, but all are united by the absence
and loss of something precious: a son, a husband, health, affection.
PMID- 28693350
TI - Proteogenomics approaches for studying cancer biology and their potential in the
identification of acute myeloid leukemia biomarkers.
AB - INTRODUCTION: Mass spectrometry (MS)-based proteomics has become an indispensable
tool for the characterization of the proteome and its post-translational
modifications (PTM). In addition to standard protein sequence databases,
proteogenomics strategies search the spectral data against the theoretical
spectra obtained from customized protein sequence databases. Up to date, there
are no published proteogenomics studies on acute myeloid leukemia (AML) samples.
Areas covered: Proteogenomics involves the understanding of genomic and proteomic
data. The intersection of both datatypes requires advanced bioinformatics skills.
A standard proteogenomics workflow that could be used for the study of AML
samples is described. The generation of customized protein sequence databases as
well as bioinformatics tools and pipelines commonly used in proteogenomics are
discussed in detail. Expert commentary: Drawing on evidence from recent cancer
proteogenomics studies and taking into account the public availability of AML
genomic data, the interpretation of present and future MS-based AML proteomic
data using AML-specific protein sequence databases could discover new biological
mechanisms and targets in AML. However, proteogenomics workflows including
bioinformatics guidelines can be challenging for the wide AML research community.
It is expected that further automation and simplification of the bioinformatics
procedures might attract AML investigators to adopt the proteogenomics strategy.
PMID- 28693351
TI - Associations Between Community Sociodemographics and Performance in HEDIS Quality
Measures: A Study of 22 Medical Centers in a Primary Care Network.
AB - Evaluation and payment for health plans and providers have been increasingly tied
to their performance on quality metrics, which can be influenced by patient- and
community-level sociodemographic factors. The aim of this study was to examine
whether performance on Healthcare Effectiveness Data and Information Set (HEDIS)
measures varied as a function of community sociodemographic characteristics at
the primary care clinic level. Twenty-two primary care sites of a large
multispecialty group practice were studied during the period of April 2013 to
June 2016. Significant associations were found between sites' performance on
selected HEDIS measures and their neighborhood sociodemographic characteristics.
Outcome measures had stronger associations with sociodemographic factors than did
process measures, with a range of significant correlation coefficients (absolute
value, regardless of sign) from 0.44 to 0.72. Sociodemographic factors accounted
for as much as 25% to 50% of the observed variance in measures such as HbA1c or
blood pressure control.
PMID- 28693352
TI - Transvaginal sonographic assessment of cervix in prediction of admission to
delivery interval in preterm premature rupture of membranes.
AB - OBJECTIVE: To assess the usefulness of cervical parameters measured by
transvaginal sonography, that is, cervical length and posterior cervical angle,
in predicting the admission to delivery interval in women with preterm rupture of
membranes. METHODS: This prospective study was conducted in a tertiary care
centre in South India. Women with preterm premature rupture of membranes at 28-34
weeks, confirmed clinically, not in labour and presenting within 24 hours to
hospital were included. We evaluated the relationship between latency interval
and transvaginal sonographic parameters (cervical length and posterior cervical
angle), parity, age, Amniotic Fluid Index (AFI), total leucocyte count at
admission using Cox proportional hazards model. RESULTS: Mean time interval
between the membrane rupture and delivery was 96.9 h. Majority of the women
(63.8% (n = 51)) delivered within 48 hours. Transvaginal sonographic cervical
length was not shown to be associated with latency interval (p = .559), whereas.
Posterior cervical angle was shown to be significantly associated with the
interval (hazard ratio 1.03, 95%CI: 1.01-1.06; p = .003) Conclusions: Posterior
cervical angle assessment using transvaginal sonography is an useful tool in the
assessing the latency interval in women with preterm premature rupture of
membranes (PPROM). This could help in counselling and planning timely referral to
centres with neonatal facilities.
PMID- 28693353
TI - Injury Characteristics of Low-Energy Lisfranc Injuries Compared With High-Energy
Injuries.
AB - BACKGROUND: Lisfranc injuries result from high- and low-energy mechanisms though
the literature has been more focused on high-energy mechanisms. A comparison of
high-energy (HE) and low-energy (LE) injury patterns is lacking. The objective of
this study was to report injury patterns in LE Lisfranc joint injuries and
compare them to HE injury patterns. METHODS: Operative Lisfranc injuries were
identified over a 5-year period. Patient demographics, mechanism of injury,
injury pattern, associated injuries, missed diagnoses, clinical course, and
imaging studies were reviewed and compared. HE mechanism was defined as motor
vehicle crash, motorcycle crash, direct crush, and fall from greater than 4 feet
and LE mechanism as athletic activity, ground level twisting, or fall from less
than 4 feet. Thirty-two HE and 48 LE cases were identified with 19.3 months of
average follow-up. RESULTS: There were no differences in demographics or missed
diagnosis frequency (21% HE vs 18% LE). Time to seek care was not significantly
different. HE injuries were more likely to have concomitant nonfoot fractures
(37% vs 6%), concomitant foot fractures (78% vs 4%), cuboid fractures (31% vs
6%), metatarsal base fractures (84% vs 29%), displaced intra-articular fractures
(59% vs 4%), and involvement of all 5 rays (23% vs 6%). LE injuries were more
commonly ligamentous (68% vs 16%), with fewer rays involved (2.7 vs 4.1).
CONCLUSIONS: LE mechanisms were a more common cause of Lisfranc joint injury in
this cohort. These mechanisms generally resulted in an isolated, primarily
ligamentous injury sparing the lateral column. Both types had high rates of
missed injury that could result in delayed treatment. Differences in injury
patterns could help direct future research to optimize treatment algorithms.
LEVEL OF EVIDENCE: Level III, comparative series.
PMID- 28693354
TI - Perinatal outcomes of congenital heart disease after emergent neonatal cardiac
procedures.
AB - PURPOSE: We compared outcome of neonates with prenatal and post-natal diagnosis
of congenital heart disease presenting in our paediatric heart centre between
March 2005 and May 2015 who underwent an emergent intervention within 48 h post
partum. MATERIALS AND METHODS: In 52/111 (46.8%) with emergent intervention,
congenital heart disease was diagnosed prenatally, in 59/111 (53.2%) with no
specialized foetal echocardiography, diagnosis was made post-natally. In 98/111
(88.2%), 30-day outcome was known. RESULTS: Regarding the entire cohort, 30-day
survival did not differ significantly in prenatal and post-natal diagnosis group
(71.2 vs. 72.9%; p > .1). Infants with prenatal diagnosis were more likely to be
born by caesarean section (59.6% vs. 33.9%, p = .01). Those with post-natal
diagnosis had a higher need for intubation (32.7% vs. 52.5%; p < .05). Subgroup
analysis of HLH/HLHC (hypoplastic left heart/hypoplastic left heart complex)
patients revealed higher number of deaths within 30 days of life in the post
natal diagnosis group, although the difference did not reach statistical
significance (5/7, 71.4% vs. 5/20, 25.0%; p = .075). CONCLUSION: For newborns who
require emergent neonatal cardiac procedures, our results point towards a lower
death rate after prenatal diagnosis of HLH/HLHC.
PMID- 28693355
TI - Postsorafenib systemic treatments for hepatocellular carcinoma: questions and
opportunities after the regorafenib trial.
AB - The search for systemic therapies for hepatocellular carcinoma has been
characterized by difficulties and failures. Despite recent progresses, many
issues are still to be settled. In particular, the development of drugs
inhibiting different neoplastic pathways remains a priority for patients
intolerant or resistant to antiangiogenic drugs. This task may be daunting, as
previous failures extensively demonstrated. We aimed to identify the future
perspective of postsorafenib trials analyzing the strengths and the critical
points of past and currently undergoing studies, in the light of the most recent
evidences in the field. We identified various points (including stratification,
biomarkers, end points, radiologic criteria of response, treatment beyond
radiologic progression) that should be considered by future trials to reduce the
risks of failure.
PMID- 28693356
TI - Contemporary practice patterns in the use of amniocentesis for fetal lung
maturity.
AB - PURPOSE: Fetal lung maturity (FLM) testing has been performed to help direct
delivery timing in complex obstetrical conditions. We explored current practice
patterns of FLM testing attempting to identify factors affecting its use.
MATERIALS AND METHODS: We distributed a 31-question survey to obstetricians and
perinatologists that examined practice characteristics potentially affecting FLM
usage. Logistic regression measured associations between these factors and test
utilization. Weighted averages were calculated for conditions in which
respondents considered FLM testing helpful. RESULTS: Three hundred four surveys
were completed. The response rate for respondents actively practicing obstetrics
was 52%. The majority of respondents utilize FLM testing; however, 80% reported a
decline in use over the past five years with 64% citing "published guidelines" as
the reason. Respondents found FLM testing most applicable for poorly dated
pregnancies. After an immature FLM test, 44% of respondents administer antenatal
corticosteroids in the late-preterm period. None of the factors surveyed were
significantly associated with FLM testing use. CONCLUSION: The majority of
respondents use FLM testing although significant factors contributing to its use
were not identified. We discover a high frequency of antenatal corticosteroid
administration beyond 34 weeks gestational age in response to immature FLM
indices that may be an area for future study.
PMID- 28693357
TI - Effect of acute ambient temperature exposure on cardio-pulmonary and respiratory
kinetics in men.
AB - AIM: The goal of the study was to compare the kinetic responses of heart rate
(HR) and pulmonary (VO2pulm) and muscular (VO2musc) oxygen uptake during dynamic
leg exercise across different acute ambient temperature conditions in a climatic
chamber. METHODS: Thirteen physically healthy, active, male volunteers
demonstrated pseudorandom binary sequence (PRBS) work rate (WR) changes between
30 and 80 W at 15 degrees C, 25 degrees C and 35 degrees C, respectively. HR
was measured beat-to-beat using an echocardiogram and VO2pulm by breath-by-breath
gas exchange; VO2musc estimations were assessed by applying a circulatory model
and cross-correlation functions. RESULTS: No significant differences were
observed across the various temperature conditions in each case for HR, VO2pulm
or VO2musc kinetics (p > 0.05). Baroreflex regulation based on HR kinetics does
not seem to be influenced between ambient temperatures of 15 degrees C and 35
degrees C during dynamic exercise. CONCLUSIONS: The results imply that ambient
temperatures of 15 degrees C, 25 degrees C and 35 degrees C have no effect on
HR, VO2pulm or VO2musc kinetics during dynamic moderate exercise. The applied
approach may be of interest for assessments of the cardio-pulmonary and
respiratory health statuses of individuals working or performing sports in
extreme temperature environments. Furthermore, differentiation between systemic
(e.g. cardio-dynamic: HR) and specific (e.g. exercising tissues: VO2musc)
determinants of the relevant physiological systems may improve the evaluation of
an individual's health status.
PMID- 28693358
TI - Anti-steatosis compounds from leaves of Mallotus furetianus.
AB - There is no drug administration-approved therapy for non-alcoholic fatty liver
disease (NAFLD) and non-alcoholic steatohepatitis (NASH). In this study, eight
compounds, gallic acid (1), methyl gallate (2), corilagin (3), 3,4,8,9,10
pentahydroxydibenzo[b,d]pyran-6-one (4), repandinin B (5), (Z)-3-hexenyl-beta-D
glucopyranoside (6), (+)-lyoniresinol-3alpha-O-alpha-L-rhamnopyranoside (7) and
mallophenol A (8) were isolated from the active fractions of Mallotus furetianus.
Three compounds, (6, 7 and 8) revealed potent anti-steatosis activity in the
oleic acid (OA)-induced steatosis cell model, with the minimum effective
concentration of 0.05 (6), 0.0005 (7) and 0.0005 (8) MUg/mL, which were much
lower than the control compound, fibrate (72.4 MUg/mL).
PMID- 28693359
TI - Coagulation monitoring correlation with heparin dose in pediatric extracorporeal
life support.
AB - OBJECTIVES: Extracorporeal Life Support (ECLS) risks thrombotic and hemorrhagic
complications. Optimal anti-coagulation monitoring is controversial. We compared
coagulation tests evaluating the heparin effect in pediatric ECLS. METHODS: A
retrospective study of children (<18yrs) undergoing ECLS over 12 months in a
tertiary pediatric intensive care unit (PICU). Variables included anti-Factor Xa
activity (anti-Xa), activated partial thromboplastin time (aPTT), activated
clotting time (ACT) and thromboelastogram (TEG(r)6s) parameters: ratio and delta
reaction (R) times (the ratio and difference, respectively, between R times in
kaolin assays with and without heparinase). Test results were correlated with
unfractionated heparin infusion rate (IU/kg/hr) at the time of sampling. Mean
test results of each ECLS run were evaluated according to the presence/absence of
complications. RESULTS: Thirty-two ECLS runs (31 patients) generated 695 data
points for correlation. PICU mortality was 22% and the thrombotic complication
rate was 66%. The proportion of variation in coagulation test results explained
by heparin dose was 13.3% for anti-Xa, 11.9% for ratio R time, and 9.9% for delta
R time, compared with <1% for ACT and aPTT. Incorporating individual variation,
age and antithrombin activity in a model with heparin dose explained less than
50% of the variation in test results. Correlation varied according to age, day of
ECLS run and between individuals, with parallel dose-response lines noted between
patients. Significantly lower mean anti-Xa was observed in PICU non-survivors and
runs with thrombosis. CONCLUSION: Lower anti-Xa was observed in ECLS runs with
complications. Although absolute results from anti-Xa and TEG6(r)s showed the
best correlation with heparin dose, a large proportion of variation in results
was unexplained by heparin, while dose response was similar between individuals.
Population pharmacokinetic/pharmacodynamic modelling is required, as well as
prospective trials to delineate the superior means of adjusting heparin therapy
to prevent adverse clinical outcomes.
PMID- 28693360
TI - The Hopkins Verbal Learning Test: an in-depth analysis of recall patterns.
AB - One of the earliest signs of dementia is memory issues and verbal word lists,
such as the Hopkins Verbal Learning Test (HVLT), are successfully used for
screening. To gain insight in how memory is affected in dementia, and to further
improve the efficacy of the HVLT, in-depth analysis of the recall patterns of
dementia cases and controls was conducted. Dementia cases and controls were
matched for factors that can affect performance, such as age, gender and
education level. Word frequency, syllable length, and orthographic neighbourhood
size did not differ in the Indonesian version of the HVLT, nor did these
characteristics affect recall. However dementia cases showed consistent and poor
recall across the three trials; with the worst recall for the "human shelter"
category and best recall for the "animals" category. Dementia cases also showed
impaired accessibility of all categories with reduced subsequent recall from
accessed categories and reduced primacy and recency levels. Finally, dementia
cases exhibited lower levels of re-remembering and recalling new words, and
higher levels of immediate forgetting and never recalling words. It was concluded
that utilising the extra information provided by the in-depth analyses of the
recall patterns could be beneficial to improve dementia screening.
PMID- 28693361
TI - Systemic effects of H2S inhalation at human equivalent dose of pathologic
halitosis on rats.
AB - OBJECTIVES: Halitosis is composed by hundreds of toxic gases. It is still not
clear whether halitosis gases self-inhaled by halitosis patients cause side
effects. The aim of the study was to investigate the effect of H2S inhalation at
a low concentration (human equivalent dose of pathologic halitosis) on rats.
MATERIALS AND METHODS: The threshold level of pathologic halitosis perceived by
humans at 250 ppb of H2S was converted to rat equivalent concentration (4.15
ppm). In the experimental group, 8 rats were exposed to H2S via continuous
inhalation but not the control rats. After 50 days, blood parameters were
measured and tissue samples were obtained from the brain, kidney and liver and
examined histopathologically to determine any systemic effect. RESULTS: While
aspartate transaminase, creatine kinase-MB and lactate dehydrogenase levels were
found to be significantly elevated, carbondioxide and alkaline phosphatase were
decreased in experimental rats. Other blood parameters were not changed
significantly. Experimental rats lost weight and became anxious.
Histopathological examination showed mononuclear inflammatory cell invasion in
the portal areas, nuclear glycogen vacuoles in the parenchymal area, single-cell
necrosis in a few foci, clear expansion in the central hepatic vein and
sinusoids, hyperplasia in Kupffer cells and potential fibrous tissue expansion in
the portal areas in the experimental rats. However, no considerable histologic
damage was observed in the brain and kidney specimens. CONCLUSIONS: It can be
concluded that H2S inhalation equivalent to pathologic halitosis producing level
in humans may lead to systemic effects, particularly heart or liver damage in
rats.
PMID- 28693362
TI - Veterinary utility of dried blood spots for analysis of toxic chlorinated
hydrocarbons.
AB - Dried blood spots (DBS) on filter paper provide a simple and convenient means of
collecting, storing and shipping samples for veterinary diagnostics related to
toxin exposures. This paper presents validation data on analysis of DBS for
chlorinated persistent organic pollutants, specifically 4,4'-dichloro-diphenyl
trichloroethane (4,4'-DDT) and its breakdown product 4,4'-dichlorodiphenyl
dichloroethylene (4,4'-DDE), lindane and a representative polychlorinated
biphenyl (PCB) congener PCB-153. Analysis was by gas chromatography with electron
capture detection (GC-ECD). The method required one 12.5 mm diameter spot
representing application of 50 MUL of blood, and working limits of detection
(LOD) for each of the compounds was 5 ppb. Data are presented on development and
description of the method, assay precision, LOD and quantitation, linearity,
accuracy, specificity, effects of long-term storage and ruggedness. The method
was also applied to 27 avian DBS, and 4,4'-DDE was detected in the majority of
samples.
PMID- 28693363
TI - Prognostic impact of incomplete hematologic count recovery and minimal residual
disease on outcome in adult acute lymphoblastic leukemia at the time of second
complete response.
AB - Outcomes of relapsed adult acute lymphoblastic leukemia (ALL) have improved over
time with the introduction of new therapies as well as better supportive care.
However, there is still a need for easy-to-use and accurate prognostic tools for
patients in first relapse. Whether complete response (CR) with incomplete count
recovery (CRh) can be grouped with CR in relapsed ALL trials has not been
formally studied. We analyzed 106 ALL patients at first relapse who were treated
at three academic centers and achieved CR/CRh. White blood cell count at initial
diagnosis and receiving hematopoietic cell transplant (HCT) were independent
predictors of overall survival after relapse, while minimal residual disease
(MRD) positivity and performance of HCT were predictors of relapse free survival
(RFS). Patients who achieved MRD negativity and underwent HCT had the best
outcomes. Our results suggest that MRD is a more powerful predictor of outcome
than CRh.
PMID- 28693364
TI - Serum uric acid is positively associated with pulmonary function in Korean health
screening examinees.
AB - OBJECTIVES: To determine whether level of serum uric acid (SUA) is linked to
pulmonary function in health screening examinees without overt medical
conditions. METHODS: We performed a cross-sectional study on 69,928 Koreans that
participated in an annual health check. RESULTS: Percent predicted forced vital
capacity (FVC%) and forced expiratory volume in 1 s (FEV1%) were positively
correlated with SUA in both genders (FVC%: r = .361; FEV1%: r = .314 in males and
FVC%: r = .413; FEV1%: r = .382 in females, all p < .001). When the 2nd, 3rd and
lowest FEV1% quartile were compared to the highest quartile group (the reference)
by regression analysis, the adjusted ORs for hyperuricemia in males were 0.876
(95% CI, 0.809-0.949), 0.631 (0.574-0.695), and 0.311 (0.278-0.349),
respectively. The adjusted ORs for hyperuricemia when the 2nd, 3rd and lowest
FEV1% quartile were compared to the highest quartile in males were 0.791 (95% CI,
0.729-0.859), 0.565 (0.513-0.623), and 0.302 (0.270-0.337), respectively (p for
trend <.001). Similarly, the adjusted OR of having hyperuricemia in females
decreased significantly across FEV1% and FVC% quartile groups compared to the
reference. CONCLUSIONS: Hyperuricemia may have a positive effect on pulmonary
function in middle aged healthy population.
PMID- 28693365
TI - Behavior of Xeno-Transplanted Undifferentiated Human Induced Pluripotent Stem
Cells Is Impacted by Microenvironment Without Evidence of Tumors.
AB - Human pluripotent stem cells (hPSC) have great clinical potential through the use
of their differentiated progeny, a population in which there is some concern over
risks of tumorigenicity or other unwanted cellular behavior due to residual hPSC.
Preclinical studies using human stem cells are most often performed within a
xenotransplant context. In this study, we sought to measure how undifferentiated
hPSC behave following xenotransplant. We directly transplanted undifferentiated
human induced pluripotent stem cells (hIPSC) and human embryonic stem cells
(hESC) into the adult mouse brain ventricle and analyzed their fates. No tumors
or precancerous lesions were present at more than one year after transplantation.
This result differed with the tumorigenic capacity we observed after
allotransplantation of mouse ESC into the mouse brain. A substantial population
of cellular derivatives of undifferentiated hESC and hIPSC engrafted, survived,
and migrated within the mouse brain parenchyma. Within brain structures,
transplanted cell distribution followed a very specific pattern, suggesting the
existence of distinct microenvironments that offer different degrees of
permissibility for engraftment. Most of the transplanted hESC and hIPSC that
developed into brain cells were NeuN+ neuronal cells, and no astrocytes were
detected. Substantial cell and nuclear fusion occurred between host and
transplanted cells, a phenomenon influenced by microenvironment. Overall, hIPSC
appear to be largely functionally equivalent to hESC in vivo. Altogether, these
data bring new insights into the behavior of stem cells without prior
differentiation following xenotransplantation into the adult brain.
PMID- 28693367
TI - A comparison of the college experience for students with and without
disabilities.
AB - Students with intellectual and developmental disabilities (IDD) have joined the
ranks of college students in pursuit of personal independence, community
integration, and employment. To achieve these aims, there is a need for a strong
understanding of the college experience for students with IDD, including
identification of the academic, social, and personal challenges they face as well
as the supports that are available to address those challenges. This research
provides preliminary insights into the college experience for students with IDD
by comparing the perceptions, attitudes, and activities of students with IDD to
those of students without disabilities and students with mild learning
disabilities (MLD). Our data suggest a number of similarities in the college
experience for students with and without disabilities such as similar influences
from family and teachers with respect to attending college. In addition, some
surprising advantages expressed by students with IDD were found, such as
reporting greater ease in developing close friendships than students with MLD.
Considerations and discussion on the ways in which students with IDD benefit from
the additional supports and services provided to them are also discussed.
PMID- 28693366
TI - Idarucizumab for Dabigatran Reversal - Full Cohort Analysis.
AB - BACKGROUND: Idarucizumab, a monoclonal antibody fragment, was developed to
reverse the anticoagulant effect of dabigatran. METHODS: We performed a
multicenter, prospective, open-label study to determine whether 5 g of
intravenous idarucizumab would be able to reverse the anticoagulant effect of
dabigatran in patients who had uncontrolled bleeding (group A) or were about to
undergo an urgent procedure (group B). The primary end point was the maximum
percentage reversal of the anticoagulant effect of dabigatran within 4 hours
after the administration of idarucizumab, on the basis of the diluted thrombin
time or ecarin clotting time. Secondary end points included the restoration of
hemostasis and safety measures. RESULTS: A total of 503 patients were enrolled:
301 in group A, and 202 in group B. The median maximum percentage reversal of
dabigatran was 100% (95% confidence interval, 100 to 100), on the basis of either
the diluted thrombin time or the ecarin clotting time. In group A, 137 patients
(45.5%) presented with gastrointestinal bleeding and 98 (32.6%) presented with
intracranial hemorrhage; among the patients who could be assessed, the median
time to the cessation of bleeding was 2.5 hours. In group B, the median time to
the initiation of the intended procedure was 1.6 hours; periprocedural hemostasis
was assessed as normal in 93.4% of the patients, mildly abnormal in 5.1%, and
moderately abnormal in 1.5%. At 90 days, thrombotic events had occurred in 6.3%
of the patients in group A and in 7.4% in group B, and the mortality rate was
18.8% and 18.9%, respectively. There were no serious adverse safety signals.
CONCLUSIONS: In emergency situations, idarucizumab rapidly, durably, and safely
reversed the anticoagulant effect of dabigatran. (Funded by Boehringer Ingelheim;
RE-VERSE AD ClinicalTrials.gov number, NCT02104947 .).
PMID- 28693368
TI - What Reading Disability? Evidence for Multiple Latent Profiles of Struggling
Readers in a Large Russian Sibpair Sample With at Least One Sibling at Risk for
Reading Difficulties.
AB - In this study, we performed a latent profile analysis of reading and related
skills in a large ( n = 733) sibpair sample of Russian readers at risk for
reading difficulties. The analysis suggested the presence of seven latent
profiles, of which two were characterized by relatively high performance on
measures of spelling and reading comprehension and the remaining five included
severely as well as moderately affected readers with deficits in the domains of
phonological, orthographic, and morphological processing. The results suggest
that the development and manifestation of reading difficulties in Russian is
mappable on a complex pattern of interactions between different types and
severities of processing deficits. The results point to the psychological reality
of multiple different suboptimal patterns of deficits in reading and reading
related skills and support the multifactorial view of the disorder, with
intriguing implications for future neurobiological studies.
PMID- 28693369
TI - Subjective health complaints and exposure to peer victimization among disabled
and non-disabled adolescents: A population-based study in Sweden.
AB - AIMS: To investigate subjective health complaints (SHCs) (psychological and
somatic, respectively) among disabled and non-disabled adolescents, focusing on
the impact of traditional bullying and cyber harassment, and furthermore to
report psychological and somatic SHCs across different types of disability.
METHODS: Data from the public health survey of children and adolescents in
Scania, Sweden, 2012 was used. A questionnaire was answered anonymously in school
by 9791 students in the 9th grade (response rate 83%), and 7533 of these with
valid answers on key questions were included in this study. Associations with
daily SHCs were investigated by multi-adjusted logistic regression analyses.
RESULTS: Any disability was reported by 24.1% of boys and 22.0% of girls.
Disabled students were more exposed to cyber harassment (boys: 20.0%; girls:
28.2%) than non-disabled peers (boys: 11.8%; girls: 18.1%). Exposure to
traditional bullying showed the same pattern but with a lower prevalence.
Disabled students had around doubled odds of both daily psychological SHCs and
daily somatic SHCs in the fully adjusted models. In general, the odds increased
with exposure to cyber harassment or traditional bullying and the highest odds
were seen among disabled students exposed to both cyber harassment and
traditional bullying. Students with ADHD/ADD had the highest odds of daily
psychological SHCs as well as exposure to traditional bullying across six
disability types. CONCLUSIONS: Disabled adolescents report poorer health and are
more exposed to both traditional bullying and cyber harassment. This public
health issue needs more attention in schools and in society in general.
PMID- 28693370
TI - Toward a Graded Psycholexical Space Mapping Model: Sublexical and Lexical
Representations in Chinese Character Reading Development.
AB - Following a review of contemporary models of word-level processing for reading
and their limitations, we propose a new hypothetical model of Chinese character
reading, namely, the graded lexical space mapping model that characterizes how
sublexical radicals and lexical information are involved in Chinese character
reading development. The underlying assumption of this model is that Chinese
character recognition is a process of competitive mappings of phonology,
semantics, and orthography in both lexical and sublexical systems, operating as
functions of statistical properties of print input based on the individual's
specific level of reading. This model leads to several testable predictions
concerning how the quasiregularity and continuity of Chinese-specific radicals
are organized in memory for both child and adult readers at different
developmental stages of reading.
PMID- 28693371
TI - Who is 'Molly'? MDMA adulterants by product name and the impact of harm-reduction
services at raves.
AB - Methylenedioxymethamphetamine (MDMA), often sold as 'Ecstasy' or 'Molly', is
commonly used at music festivals and reported to be responsible for an increase
in deaths over the last decade. Ecstasy is often adulterated and contains
compounds that increase morbidity and mortality. While users and clinicians
commonly assume that products sold as Molly are less-adulterated MDMA products,
this has not been tested. Additionally, while pill-testing services are sometimes
available at raves, the assumption that these services decrease risky drug use
has not been studied. This study analyzed data collected by the pill-testing
organization, DanceSafe, from events across the United States from 2010 to 2015.
Colorimetric reagent assays identified MDMA in only 60% of the 529 samples
collected. No significant difference in the percentage of samples testing
positive for MDMA was determined between Ecstasy and Molly. Individuals were
significantly less likely to report intent to use a product if testing did not
identify MDMA (relative risk (RR) = 0.56, p = 0.01). Results suggest that Molly
is not a less-adulterated substance, and that pill-testing services are a
legitimate harm-reduction service that decreases intent to consume potentially
dangerous substances and may warrant consideration by legislators for legal
protection. Future research should further examine the direct effects of pill
testing services and include more extensive pill-testing methods.
PMID- 28693372
TI - Prostaglandin E Pathway in Uterine Tissue During Window of Preimplantation in
Female Mice Mated With Intact and Seminal Vesicle-Excised Male.
AB - Prostaglandin E2 (PGE2) has been introduced as an important factor for embryo
implantation. So the present study was carried out to evaluate the effect of
seminal fluid (SF) on PGE2 pathway in uterus tissues of mice during window of
preimplantation. The messenger RNA (mRNA) expressions of microsomal PGE synthase
(mPGES) and cytosolic PGE synthase (cPGES) as well as protein expression of PGE
receptor 2 and 4 (EP2 and EP4) were determined in uterine tissue of control and
seminal vesicle-excised (SVX)-mated female mice during days 1 to 5 of pregnancy
using real-time polymerase chain reaction (qRT-PCR) and Western blotting,
respectively. We found that mRNA expression of mPGES at day 1 and 2 of pregnancy
was significantly higher in the control group than the SVX-mated group ( P <
.05), but such result was not obtained for cPGES expression. The protein levels
of EP2 at day 1 to 4 of pregnancy were significantly higher in the control group
compared with the SVX-mated group ( P < .05), also the EP4 levels were
significantly different between the control and SVX-mated groups at the first day
of pregnancy ( P < .05). Implantation rate was higher in the control group and
also there were positive correlations between mPGES and EP2 expressions in the
fifth day of pregnancy with implantation rate. Our results demonstrated
significant effect of SF on uterine expressions of the evaluated factors,
especially mPGES and EP2. Regarding the correlations between levels of these
factors and implantation rate, we suggest that possibly one of the important
mechanisms of SF in affecting female pregnancy is through mPGES and EP2.
PMID- 28693373
TI - Prenatal Growth Patterns and Birthweight Are Associated With Differential DNA
Methylation and Gene Expression of Cardiometabolic Risk Genes in Human Placentas:
A Discovery-Based Approach.
AB - Inherent genetic programming and environmental factors affect fetal growth in
utero. Epidemiologic data in growth-altered fetuses, either intrauterine growth
restricted (IUGR) or large for gestational age (LGA), demonstrate that these
newborns are at increased risk of cardiometabolic disease in adulthood. There is
growing evidence that the in utero environment leads to epigenetic modification,
contributing to eventual risk of developing heart disease or diabetes. In this
study, we used reduced representation bisulfite sequencing to examine genome-wide
DNA methylation variation in placental samples from offspring born IUGR, LGA, and
appropriate for gestational age (AGA) and to identify differential methylation of
genes important for conferring risk of cardiometabolic disease. We found that
there were distinct methylation signatures for IUGR, LGA, and AGA groups and
identified over 500 differentially methylated genes (DMGs) among these group
comparisons. Functional and gene network analyses revealed expected relationships
of DMGs to placental physiology and transport, but also identified novel pathways
with biologic plausibility and potential clinical importance to cardiometabolic
disease. Specific loci for DMGs of interest had methylation patterns that were
strongly associated with anthropometric presentations. We further validated
altered gene expression of these specific DMGs contributing to vascular and
metabolic diseases (SLC36A1, PTPRN2, CASZ1, IL10), thereby establishing
transcriptional effects toward assigning functional significance. Our results
suggest that the gene expression and methylation state of the human placenta are
related and sensitive to the intrauterine environment, as it affects fetal growth
patterns. We speculate that these observed changes may affect risk for offspring
in developing adult cardiometabolic disease.
PMID- 28693374
TI - John F. Kennedy's back: chronic pain, failed surgeries, and the story of its
effects on his life and death.
AB - The 35th president of the United States, John F. Kennedy (JFK), experienced
chronic back pain beginning in his early 20s. He underwent a total of 4 back
operations, including a discectomy, an instrumentation and fusion, and 2
relatively minor surgeries that failed to significantly improve his pain. The
authors examined the nature and etiology of JFK's back pain and performed a
detailed investigation into the former president's numerous medical evaluations
and treatment modalities. This information may lead to a better understanding of
the profound effects that JFK's chronic back pain and its treatment had on his
life and presidency, and even his death.
PMID- 28693375
TI - Editorial. John F. Kennedy's back.
PMID- 28693376
TI - Ibrutinib-induced acute liver failure.
PMID- 28693377
TI - Effect of floor reaction ankle-foot orthosis on crouch gait in patients with
cerebral palsy: What can be expected?
AB - BACKGROUND: Floor reaction ankle-foot orthoses are commonly prescribed to improve
knee extension of children with cerebral palsy having crouch gait. Their
effectiveness is debated. Therefore, the objective of this study is to optimize
current prescription criteria for the improvement of crouch gait. STUDY DESIGN:
Cross-sectional interventional study. METHODS: A total of 22 patients with
bilateral spastic cerebral palsy, between 6 and 17 years, Gross Motor Function
Classification System II-IV participated in this study. Instrumented gait
analysis was done under three conditions: barefoot, shoed, and with orthotics.
Patients were divided into two groups: good and non-responders with more and less
than 8.8 degrees improvement of knee extension during walking, respectively. A
multiple predictor analysis was done on parameters that were different between
groups. RESULTS: In total, 12 of 22 patients showed good response in knee
extension with a mean change of 17 degrees (standard deviation = 5 degrees ).
Good responders showed a significantly smaller walking velocity, knee extension
strength, ankle plantarflexion strength, and greater external foot progression
angle compared to non-responders. Foot progression angle together with ankle
plantarflexion strength explained 37% of the variance in improvement of knee
extension. CONCLUSION: With appropriate patient selection, an improvement of
crouch gait by ankle-foot orthoses of 17 degrees (standard deviation = 5 degrees
) can be expected. Patients with slow velocity, weak plantarflexors, and external
foot progression benefit most. Joint contractures were no contraindications.
Clinical relevance This study showed that gait in patients with low functional
level benefit most from ankle-foot orthoses. Unlike in patients with higher
functional status, contractures of hip, knee, and ankle did not reduce the
positive effects on gait. The suggested prescription criteria may help to better
select appropriate patients for orthotics.
PMID- 28693378
TI - Effects of load carriage and work boots on lower limb kinematics of industrial
workers.
AB - Load and footwear condition are two crucial elements varying the kinematic
responses during walking, which probably lead to chronic injury. Fifteen healthy
male individuals with no obvious gait abnormalities participated in this study.
Apart from a no-load condition, four external load conditions with two load
levels were investigated. Work boots were compared with running shoes to
determine footwear effects. Significant impacts were found for lower limb range
of motion at certain joints when carrying loads. A greater hip and ankle flexion
extension while wearing the work boots indicated that participants needed to lift
the leg higher to complete toe clearance off the walking surface. Work boots also
increased the vertical excursion of the center of body mass, which may impact
body balance and induce falling. No significant influencing pattern of carrying
modes was found, which was probably due to the light load and relatively stable
mode of shoulder carrying.
PMID- 28693379
TI - Incidence of osteonecrosis of the jaw in patients with bone metastases treated
sequentially with bisphosphonates and denosumab.
AB - OBJECTIVES: Osteonecrosis of the jaw (ONJ) is a serious adverse event of bone
resorption inhibitors (BRIs), such as bisphosphonates and denosumab.
Bisphosphonates and denosumab inhibit osteoclast function through different
pharmacological effects and bisphosphonates are retained in bone for several
months to years. Sequential treatment with bisphosphonates and denosumab might
lead to an overlapping treatment effect, due to the addition of the effect of
denosumab on the residual bisphosphonate effect. Therefore, the aim of our study
was to investigate if switching from denosumab to bisphosphonates is associated
with a higher incidence of ONJ. METHODS: We retrospectively reviewed records of
patients with solid tumors and bone metastases treated with denosumab after prior
treatment with bisphosphonates at the University Hospitals Leuven (sequential
group). Patients treated with denosumab or bisphosphonates alone were used as
control groups. RESULTS: We identified 110 patients sequentially treated with
bisphosphonates and denosumab with a median total BRI exposure of 36 months
(sequential group). Median bisphosphonates exposure was 16 months and median
denosumab exposure was 13 months. About 299 patients were included in the
bisphosphonates control group with a median bisphosphonate exposure 19 months.
About 6.7% (20/299) of patients developed ONJ. About 240 patients were included
in the denosumab control group with a median denosumab exposure 17.5 months.
About 10.0% of patients (24/240) developed ONJ. In the sequential group, 15.5% of
patients (17/110) developed ONJ. The incidence of ONJ was 1.8% (2/110), 6.3%
(6/99), 4.9% (4/82), 5.6% (3/54), and 3.4% (1/29), respectively in the first,
second, third, fourth, and fifth year of BRI exposure, an ONJ-incidence similar
to ONJ-incidence in the denosumab control group. In a time-to-ONJ-analysis, the
curves of the sequential group and the denosumab control group were overlapping.
In the sequential group, most of the ONJs occurred in the first year of denosumab
exposure and in a matched control group analysis, with correction for median BRI
exposure, ONJ cases tend to occur earlier in the sequential group compared to ONJ
cases in the bisphosphonates group. CONCLUSION: Cancer patients with bone
metastases treated with BRIs seem to have a slightly higher risk of ONJ early
after switching from bisphosphonates to denosumab compared to patients remaining
on bisphosphonates. Nevertheless, based on the global ONJ-incidence, the switch
from bisphosphonates to denosumab can be considered as safe as an equivalent
exposure to denosumab from the start on.
PMID- 28693380
TI - The binary complex of poly(PEGMA-co-MAA) hydrogel and PLGA nanoparticles as a
novel oral drug delivery system for ibuprofen delivery.
AB - To improve the bioavailability of ibuprofen (IBU), we developed a novel binary
complex of poly(PEGMA-co-MAA) hydrogel and IBU-loaded PLGA nanoparticles (IBU
PLGA NPs@hydrogels) as an oral intestinal targeting drug delivery system (OIDDS).
The IBU-loaded PLGA NPs and pH-sensitive hydrogels were obtained via the solvent
evaporation method and radical polymerization, respectively. The final OIDDS was
obtained by immersing the hydrogel chips in the IBU-loaded PLGA NPs solutions (pH
7.4) for 3 d. The size distribution and morphology of cargo-free NPs were studied
by laser granularity analyzer and transmission electron microscope (TEM). The
inner structures of the pH-sensitive hydrogel chips were observed with an S-4800
scanning electron microscope (SEM). The distribution states of IBU in the OIDDS
were also studied with X-ray diffraction (XRD) and differential scanning
calorimetry (DSC). TEM photographs illustrated that the PLGA NPs had a round
shape with an average diameter about 100 nm. Fourier transform infrared spectrum
(FTIR) confirmed the synthesis of poly(PEGMA-co-MAA) hydrogel. The SEM picture
showed that the final hydrogel had 3D net-work structures. Moreover, the
poly(PEGMA-co-MAA) hydrogel showed an excellent pH-sensitivity. The XRD and DSC
curves suggested that IBU distributed in the OIDDS with an amorphous state. The
cumulated release profiles indicated that the final OIDDS could release IBU in
alkaline environment (e.g. intestinal tract) at a sustained manner. Therefore,
the novel OIDDS could improve the oral bioavailability of IBU, and had a
potential application in drug delivery.
PMID- 28693381
TI - A meta-analysis of weekend admission and surgery for aortic rupture and
dissection.
AB - We performed a meta-analysis to determine whether weekend admission and surgery
for ruptured abdominal/thoracic aortic aneurysm (RAAA/RTAA) and acute aortic
dissection (AAD) is associated with increased mortality. MEDLINE and EMBASE were
searched from January 1946 to December 2016 using PubMed and OVID. Eligible
studies were prospective or retrospective, comparative or cohort studies
enrolling patients admitting or undergoing surgery for RAAA/RTAA/AAD and
reporting mortality after weekend (including holiday) versus weekday
admission/surgery. Our search identified 11 studies including a total of 166,195
patients. A pooled analysis of 13 adjusted odds ratios (ORs), one adjusted hazard
ratio, and one unadjusted OR from all 11 studies demonstrated a statistically
significant 32% increase in mortality with weekend admission/surgery (OR, 1.32;
95% confidence interval (CI), 1.20 to 1.45; p < 0.00001). Despite possible
publication bias disadvantageous to weekend admission/surgery based on funnel
plot asymmetry, adjustment for the asymmetry using the trim-and-fill method did
not alter the significant association of weekend admission/surgery with increased
mortality (OR, 1.21; 95% CI, 1.09 to 1.34; p = 0.0006). In conclusion, weekend
admission/surgery for ruptured abdominal/thoracic aortic aneurysm and acute
aortic dissection (AAD) may be associated with increased mortality.
PMID- 28693382
TI - miR-7 Increases Cisplatin Sensitivity of Gastric Cancer Cells Through Suppressing
mTOR.
AB - MicroRNAs have been reported to play an important role in diverse biological
processes and cancer progression. MicroRNA-7 has been observed to be
downregulated in human gastric cancer tissues, but the function of microRNA-7 in
gastric cancer has not been well investigated. In this study, we demonstrate that
the expression of microRNA-7 was significantly downregulated in 30 pairs of human
gastric cancer tissues compared to adjacent normal tissues. Enforced expression
of microRNA-7 inhibited cell proliferation and migration abilities of gastric
cancer cells, BGC823 and SGC7901. Furthermore, microRNA-7 targeted mTOR in
gastric cancer cells. In human clinical specimens, mTOR was higher expressed in
gastric cancer tissues compared with adjacent normal tissues. More interestingly,
microRNA-7 also sensitizes gastric cancer cells to cisplatin (CDDP) by targeting
mTOR. Collectively, our results demonstrate that microRNA-7 is a tumor suppressor
microRNA and indicate its potential application for the treatment of human
gastric cancer in future.
PMID- 28693383
TI - Saccharomyces cerevisiae MSA1 mRNA has a sequence for localization at the bud
tip.
AB - MSA1 mRNA encodes Msa1p, a protein associated with the SCB-binding factor (SBF)
and MCB-binding factor (MBF) complex. Msa1p promotes the transcription of G1
phase-specific genes, and is subjected to cell cycle-dependent regulation for its
abundance and subcellular localization. MSA1 mRNA and Msa1p levels oscillate in
the cell cycle with peaks at the late M/early G1 phase and early G1 phase,
respectively. Phosphorylation by CDK1 negatively regulates the nuclear
localization of Msa1p. In the present study, we identified MSA1 mRNA as a bud tip
localized mRNA in screening using a Tag-GFP system. A fragmentation analysis
revealed a sequence of ~145 bases for the bud tip localization. Endogenous MSA1
mRNA localized at the bud tip in a manner that depended on SHE2. Msa1p levels
were also affected by SHE2 in cells constitutively expressing MSA1 mRNA. These
results suggest the existence of a regulatory mechanism for Msa1p through the
localized control of MSA1 mRNA.
PMID- 28693384
TI - Eye irritation potential: palm-based methyl ester sulphonates.
AB - AIM: To evaluate eye irritation potential of palm-based methyl ester sulphonates
(MES) of different chain lengths; C12, C14, C16, C16:18. METHODS: The Bovine
Corneal Opacity and Permeability test method (BCOP), OECD Test Guideline 437, was
used as an initial step to study the inducing effect of palm-based MES on
irreversible eye damage. The second assessment involved the use of reconstructed
human corneal-like epithelium test method, OECD Test Guideline 492 using
SkinEthicTM Human Corneal Epithelium to study the potential effect of palm-based
MES on eye irritancy. The palm-based MES were prepared in 10% solution (w/v) in
deionized water and tested as a liquid and surfactant test substances whereby
both test conducted according to the liquid/surfactant treatment protocol.
RESULTS: The preliminary BCOP results showed that palm-based MES; C12, C14, C16,
C16:18 were not classified as severe eye irritants test substances with in vitro
irritancy score between 3 and the threshold level of 55. The second evaluation
using SkinEthicTM HCE model showed that palm-based MES; C12, C14, C16, C16:18 and
three commercial samples were potentially irritants to the eyes with mean tissue
viability <= 60% and classified as Category 2 according to United Nations
Globally Harmonized System of Classification and Labelling of Chemicals. However,
there are some limitations of the proposed ocular irritation classification of
palm-based MES due to insolubility of long chain MES in 10% solution (w/v) in
deionized water. CONCLUSION: Therefore, future studies to clarify the eye
irritation potential of the palm-based MES will be needed, and could include;
methods to improve the test substance solubility, use of test protocol for
solids, and/or inclusion of a benchmark anionic surfactant, such as sodium
dodecyl sulphate within the study design.
PMID- 28693385
TI - Observations From California's Delivery System Reform Incentive Payment Program.
AB - California's Delivery System Reform Incentive Payment (DSRIP) Program provided
$3.3 billion over 5 years to support 21 public hospitals improve the quality of
health care delivery and population health. The Institute for Population Health
Improvement provided technical support and quality improvement mentorship to the
California Department of Health Care Services in implementing the DSRIP Program.
This report describes the following key observations on the implementation of the
program: the need to reduce variability in data collection and management,
memorialize decision-making processes, build broad quality improvement capacity,
define and revisit improvement targets, anticipate evolution of clinical
definitions and guidelines, provide frequent feedback to participating hospitals,
engage frontline clinicians, balance short- and long-term improvement goals,
acknowledge regulatory requirements and improvement efforts that may compete for
resources, and build in shared learning and dissemination of interventions. The
authors believe this experience with implementing California's DSRIP Program may
assist other states as they implement similarly intended reform programs.
PMID- 28693386
TI - Development methodology of the novel Endoscopic stone treatment step 1 (EST s1)
training/assessment curriculum.
AB - Background Simulation based technical-skill assessment is a core topic of debate,
especially in high-risk environments. After the introduction of the E-BLUS exam
for basic laparoscopy, no more technical training/assessment urological protocols
have been developed in Europe. Objective We describe the methodology used in the
development of the novel Endoscopic Stone Treatment step 1 (EST s1) assessment
curriculum. Materials and Methods The "full life cycle curriculum development"
template was followed for curriculum development. A CTA was run to define the
most important steps and details of RIRS, in accordance with EAU Urolithiasis
guidelines. Training tasks were created between April 2015 and September 2015.
Tasks and metrics were further analyzed by a consensus meeting with the EULIS
board in February 2016. A review, aimed to study available simulators and their
accordance with task requirements, was subsequently run in London on March 2016.
After initial feedback and further tests, content validity of this protocol was
achieved during EUREP 2016. Results The EST s1 curriculum development, took 23
months. 72 participants tested the 5 preliminary tasks during EUREP 2015, with
sessions of 45 minutes each. Likert-scale questionnaires were filled-out to score
the quality of training. The protocol was modified accordingly and 25
participants tested the 4 tasks during the hands-on training sessions of the ESUT
2016 congress. 134 participants finally participated in the validation study in
EUREP 2016. During the same event 10 experts confirmed content validity by
filling-out a Likert-scale questionnaire. Conclusion We described a reliable and
replicable methodology that can be followed to develop training/assessment
protocols for surgical procedures. The expert consensus meetings, strict
adherence to guidelines and updated literature search towards an Endourology
curriculum allowed correct training and assessment protocol development. It is
the first step towards standardized simulation training in Endourology with a
potential for worldwide adoption.
PMID- 28693387
TI - The FLC Locus: A Platform for Discoveries in Epigenetics and Adaptation.
AB - Our understanding of the detailed molecular mechanisms underpinning adaptation is
still poor. One example for which mechanistic understanding of regulation has
converged with studies of life history variation is Arabidopsis thaliana
FLOWERING LOCUS C (FLC). FLC determines the need for plants to overwinter and
their ability to respond to prolonged cold in a process termed vernalization.
This review highlights how molecular analysis of vernalization pathways has
revealed important insight into antisense-mediated chromatin silencing mechanisms
that regulate FLC. In turn, such insight has enabled molecular dissection of the
diversity in vernalization across natural populations of A. thaliana. Changes in
both cotranscriptional regulation and epigenetic silencing of FLC are caused by
noncoding polymorphisms at FLC. The FLC locus is therefore providing important
concepts for how noncoding transcription and chromatin regulation influence gene
expression and how these mechanisms can vary to underpin adaptation in natural
populations.
PMID- 28693388
TI - Sending and Receiving Hedgehog Signals.
AB - Communication between cells pervades the development and physiology of metazoans.
In animals, this process is carried out by a relatively small number of signaling
pathways, each consisting of a chain of biochemical events through which
extracellular stimuli control the behavior of target cells. One such signaling
system is the Hedgehog pathway, which is crucial in embryogenesis and is
implicated in many birth defects and cancers. Although Hedgehog pathway
components were identified by genetic analysis more than a decade ago, our
understanding of the molecular mechanisms of signaling is far from complete. In
this review, we focus on the biochemistry and cell biology of the Hedgehog
pathway. We examine the unique biosynthesis of the Hedgehog ligand, its
specialized release from cells into extracellular space, and the poorly
understood mechanisms involved in ligand reception and pathway activation at the
surface of target cells. We highlight several critical questions that remain
open.
PMID- 28693389
TI - Primary care physicians' attitudes and beliefs about cancer clinical trials.
AB - BACKGROUND/AIMS: Cancer clinical trials give patients access to state-of-the-art
treatments and facilitate the translation of findings into mainstream clinical
care. However, patients from racial and ethnic minority groups remain
underrepresented in clinical trials. Primary care physicians are a trusted source
of information for patients, yet their role in decision-making about cancer
treatment and referrals to trial participation has received little attention. The
aim of this study was to determine physicians' knowledge, attitudes, and beliefs
about cancer clinical trials, their experience with trials, and their interest in
appropriate training about trials. METHODS: A total of 613 physicians in the New
York City area primarily serving patients from ethnic and racial minority groups
were invited via email to participate in a 20-min online survey. Physicians were
asked about their patient population, trial knowledge and attitudes, interest in
training, and personal demographics. Using calculated scale variables, we used
descriptive statistical analyses to better understand physicians' knowledge,
attitudes, and beliefs about trials. RESULTS: A total of 127 physicians completed
the survey. Overall, they had low knowledge about and little experience with
trials. However, they generally had positive attitudes toward trials, with 41.4%
indicating a strong interest in learning more about their role in trials, and
35.7% indicating that they might be interested. Results suggest that Black and
Latino physicians and those with more positive attitudes and beliefs were more
likely to be interested in future training opportunities. CONCLUSION: Primary
care physicians may be an important group to target in trying to improve cancer
clinical trial participation among minority patients. Future work should explore
methods of educational intervention for such interested providers.
PMID- 28693390
TI - Collaborating with nurse leaders to develop patient safety practices.
AB - Purpose The organisational level and leadership development are crucial elements
in advancing patient safety, because patient safety weaknesses are often caused
by system failures. However, little is known about how frontline leader and
director teams can be supported to develop patient safety practices. The purpose
of this study is to describe the patient safety development process carried out
by nursing leaders and directors. The research questions were: how the chosen
development areas progressed in six months' time and how nursing leaders view the
participatory development process. Design/methodology/approach Participatory
action research was used to engage frontline nursing leaders and directors into
developing patient safety practices. Semi-structured group interviews ( N = 10)
were used in data collection at the end of a six-month action cycle, and data
were analysed using content analysis. Findings The participatory development
process enhanced collaboration and gave leaders insights into patient safety as a
part of the hospital system and their role in advancing it. The chosen
development areas advanced to different extents, with the greatest improvements
in those areas with simple guidelines to follow and in which the leaders were
most participative. The features of high-reliability organisation were moderately
identified in the nursing leaders' actions and views. For example, acting as a
change agent to implement patient safety practices was challenging. Participatory
methods can be used to support leaders into advancing patient safety. However, it
is important that the participants are familiar with the method, and there are
enough facilitators to steer development processes. Originality/value Research
brings more knowledge of how leaders can increase their effectiveness in
advancing patient safety and promoting high-reliability organisation features in
the healthcare organisation.
PMID- 28693391
TI - Leading nurses: emotional intelligence and leadership development effectiveness.
AB - Purpose The purpose of this paper is to examine the effectiveness of an emotional
intelligence (EI) and leadership development education program involving 20 nurse
leaders at nursing homes. Also, it investigates the relationship between EI and
transformational leadership. Design/methodology/approach Three research questions
are posed. Correlation analysis and t-tests were conducted to answer the
questions posed. Findings The findings of this paper indicate that the EI
educational development was effective, while the personal leadership development
was not. The data also showed a positive significant relationship between EI and
transformational leadership. Research limitations/implications This paper is
limited by the small sample size; thus, a causal relationship between EI and
leadership could not be investigated. Additionally, the sample was not randomly
selected because of the commitment needed from the participants. Furthermore, the
paper was focused on nurse leaders in nursing homes, so it may not be
generalizable to other populations. Practical implications With the increasing
need for nursing home facilities and the limited training generally provided to
nurses who move into managerial roles in these facilities, it is critical for
organizations to understand the effectiveness of educational programs that exist.
Moreover, the findings of this paper may provide information that would be useful
to others who wish to develop EI and/or leadership education for nurses.
Originality/value While much research exists on EI and transformational
leadership, little of this research focuses on nurses in nursing home facilities.
Thus, this paper fills a gap in the literature.
PMID- 28693392
TI - The impact of leadership development on GP mental health commissioning.
AB - Purpose This paper aims to explore the learning needs of general practitioners
(GPs) involved in commissioning mental health provision in England, and offer an
evaluation of a leadership and commissioning skills development programme for
Mental Health Commissioners. Design/methodology/approach Retrospective mixed
method, including online mixed method survey, rating participants' knowledge,
skills, abilities, semi-structured telephone interviews and third-party
questionnaires were used. Results were analysed for significant differences using
the Wilcoxon Signed Ranks test. Open-ended responses and interview transcripts
were analysed thematically. Findings Indicative results showed that participants
perceived significant impacts in ability across eight key question groups
evaluated. Differences were found between the perceived and observed impact in
relation to technical areas covered within the programme which were perceived as
the highest scoring impacts by participants. Research limitations/implications
The indicative results show a positive impact on practice has been both perceived
and observed. Findings illustrate the value of this development programme on both
the personal development of GP Mental Health Commissioners and commissioning
practice. Although the findings of this evaluation increase understanding in
relation to an important and topical area, larger scale, prospective evaluations
are required. Impact evaluations could be embedded within future programmes to
encourage higher participant and third-party engagement. Future evaluations would
benefit from collection and analysis of attendance data. Further research could
involve patient, service user and carer perspectives on mental health
commissioning. Originality value Results of this evaluation could inform the
development of future learning programmes for mental health commissioners as part
of a national approach to improve mental health provision.
PMID- 28693393
TI - TQM implementation for the healthcare sector.
AB - Purpose The purpose of this paper is to enlarge the debate on total quality
management (TQM) implementation in the healthcare sector and to evaluate how and
whether leadership can affect TQM implementation. Design/methodology/approach
This paper is based on findings from a literature review of TQM and leadership.
The authors analysed these findings to categorise causes of a lack of leadership
in TQM programme implementations. Findings The authors propose three categories
of causes of a lack of leadership in TQM programme implementation. The first
cause is well-known: a lack of senior managers' involvement and commitment. The
second category is the "combined leadership" that occurs in large healthcare
organisations; and the third category is the influence of an external "political
leadership" on public healthcare. Research limitations/implications This paper
presents researchers with three categories of causes of failure of leadership in
TQM implementation that can be investigated. It also encourages reflections from
practitioners concerning TQM leadership in the healthcare sector. Practical
implications The authors request that practitioners reflect on ways to create or
sustain a "monolithic" leadership, especially in large organisations, to ensure a
common vision, values and attitude for unitary TQM governance. Originality/value
In an original way, this paper analyses and proposes three categories of causes
linked to a lack of TQM leadership in the healthcare sector.
PMID- 28693394
TI - An evaluation of a leadership development coaching and mentoring programme.
AB - Purpose The purpose of this paper was to determine the value and impact of the
Leadership Development - Coaching and Mentoring Programme at Counties Manukau
Health and understand how the skills gained are applied.
Design/methodology/approach Mixed-methods approach including surveys of programme
participants and senior staff and semi-structured interviews with programme
participants. Findings The survey response rate was 24.4 per cent for programme
participants and 30 per cent for senior staff. Eight programme participants
participated in semi-structured interviews. Of the 70 programme participants, 69
utilised their learning from the programme; 45 of 70 changed their approach to
managing staff; and 40 of 68 programme participants reported that meeting with
peers for triad group coaching was the most challenging aspect of the programme.
Key themes identified through interviews included: working with others; not
owning others' problems; professional support and development; coaching and
mentoring; future participants. Practical implications The majority of
participants changed their leadership behaviours as a result of the programme,
which has resulted in improved communication, a more supportive culture and
distributed leadership. These changes contribute to better patient care.
Originality value There is a paucity of evidence in the literature about the
impact of coaching and mentoring programme on leadership development and how the
skills gained in such programmes are applied in practice in a healthcare context.
This evaluation helps to address that gap.
PMID- 28693395
TI - An ideal hospital.
AB - Purpose The purpose of this paper is to explore a novel overarching strategy in
tackling the key issues raised by the recent inquiry into bullying, harassment
and discrimination in surgical practice and surgical training in Australian and
New Zealand hospitals. Design/methodology/approach The approach taken is an
analysis of the available evidence-based literature to inform the proposed
viewpoint. The theoretical subject scope presented is a discussion of how and why
the various strategies put forward in this paper should be integrated into and
led from an overarching workforce engagement platform. Findings The key themes
isolated from the Inquiry into Australian and New Zealand surgical practice
ranged from abuse of power by those in leadership positions, gender inequity in
the surgical workforce, opaque and corrupt complaints handling processes,
excessive surgical trainee working hours to bystander silence secondary to a fear
of reprisal. A workforce engagement perspective has elicited the potential to
counter various impacts, that of clinical ineffectiveness, substandard quality
and safety, inefficient medical workforce management outcomes, adverse economic
implications and the operational profitability of a hospital. Generic strategies
grounded in evidence-based literature were able to then be aligned with specific
action areas to provide a new leadership framework for addressing these impacts.
Originality/value To the author's knowledge, this is one of the first responses
providing a framework on how medical managers and hospital executives can begin
to lead a comprehensive and practical strategy for changing the existing culture
of bullying, harassment and discrimination in surgical practice by using a staff
engagement framework.
PMID- 28693396
TI - Exploring generational cohort work satisfaction in hospital nurses.
AB - Purpose Although extensive research exists regarding job satisfaction, many
previous studies used a more restrictive, quantitative methodology. The purpose
of this qualitative study is to capture the perceptions of hospital nurses within
generational cohorts regarding their work satisfaction.
Design/methodology/approach A preliminary qualitative, phenomenological study
design explored hospital nurses' work satisfaction within generational cohorts -
Baby Boomers (1946-1964), Generation X (1965-1980) and Millennials (1981-2000). A
South Florida hospital provided the venue for the research. In all, 15 full-time
staff nurses, segmented into generational cohorts, participated in personal
interviews to determine themes related to seven established factors of work
satisfaction: pay, autonomy, task requirements, administration, doctor-nurse
relationship, interaction and professional status. Findings An analysis of the
transcribed interviews confirmed the importance of the seven factors of job
satisfaction. Similarities and differences between the generational cohorts
related to a combination of stages of life and generational attributes. Practical
implications The results of any qualitative research relate only to the specific
venue studied and are not generalizable. However, the information gleaned from
this study is transferable and other organizations are encouraged to conduct
their own research and compare the results. Originality/value This study is
unique, as the seven factors from an extensively used and highly respected
quantitative research instrument were applied as the basis for this qualitative
inquiry into generational cohort job satisfaction in a hospital setting.
PMID- 28693397
TI - Bringing voice in policy building.
AB - Purpose The purpose of this paper is to describe the use of group concept mapping
(GCM) as a tool for developing a conceptual model of an episode of acute,
unscheduled care from illness or injury to outcomes such as recovery, death and
chronic illness. Design/methodology/approach After generating a literature review
drafting an initial conceptual model, GCM software (CS Global MAXTM) is used to
organize and identify strengths and directionality between concepts generated
through feedback about the model from several stakeholder groups: acute care and
non-acute care providers, patients, payers and policymakers. Through online and
in-person population-specific focus groups, the GCM approach seeks feedback,
assigned relationships and articulated priorities from participants to produce an
output map that described overarching concepts and relationships within and
across subsamples. Findings A clustered concept map made up of relational data
points that produced a taxonomy of feedback was used to update the model for use
in soliciting additional feedback from two technical expert panels (TEPs), and
finally, a public comment exercise was performed. The results were a stakeholder
informed improved model for an acute care episode, identified factors that
influence process and outcomes, and policy recommendations, which were delivered
to the Department of Health and Human Services's (DHHS) Assistant Secretary for
Preparedness and Response. Practical implications This study provides an example
of the value of cross-population multi-stakeholder input to increase voice in
shared problem health stakeholder groups. Originality/value This paper provides
GCM results and a visual analysis of the relational characteristics both within
and across sub-populations involved in the study. It also provides an assessment
of observational key factors supporting how different stakeholder voices can be
integrated to inform model development and policy recommendations.
PMID- 28693398
TI - Use of evidence-based management in healthcare administration decision-making.
AB - Purpose The purpose of this paper is to examine whether healthcare leaders use
evidence-based management (EBMgt) when facing major decisions and what types of
evidence healthcare administrators consult during their decision-making. This
study also intends to identify any relationship that might exist among adoption
of EBMgt in healthcare management, attitudes towards EBMgt, demographic
characteristics and organizational characteristics. Design/methodology/approach A
cross-sectional study was conducted among US healthcare leaders. Spearman's
correlation and logistic regression were performed using the Statistical Package
for the Social Sciences (SPSS) 23.0. Findings One hundred and fifty-four
healthcare leaders completed the survey. The study results indicated that 90 per
cent of the participants self-reported having used an EBMgt approach for decision
making. Professional experiences (87 per cent), organizational data (84 per cent)
and stakeholders' values (63 per cent) were the top three types of evidence
consulted daily and weekly for decision-making. Case study (75 per cent) and
scientific research findings (75 per cent) were the top two types of evidence
consulted monthly or less than once a month. An exploratory, stepwise logistic
regression model correctly classified 75.3 per cent of all observations for a
dichotomous "use of EBMgt" response variable using three independent variables:
attitude towards EBMgt, number of employees in the organization and the job
position. Spearman's correlation indicated statistically significant
relationships between healthcare leaders' use of EBMgt and healthcare
organization bed size ( rs = 0.217, n = 152, p < 0.01), attitude towards EBMgt (
rs = 0.517, n = 152, p < 0.01), and the number of organization employees ( rs =
0.195, n = 152, p = 0.016). Originality/value This study generated new research
findings on the practice of EBMgt in US healthcare administration decision
making.
PMID- 28693399
TI - The secret lives of children.
PMID- 28693400
TI - Formulating autism systemically: Part 2 - A 12-year prospective case study.
AB - This prospective case study illustrates the ideas on the developmental origins of
some cases of autism that were described in Part 1 of this article. We explored
and found support for several systemic hypotheses regarding the experience of
'Graeme' and his mother. Graeme's story is told prospectively from the age of 3
until 15. Three independent sources of information are reported: hypotheses from
the literature and case review in Part 1 of this article, the school's
experience, and observations from the assessments of attachment when Graeme was
turning 6. These three streams of information are integrated here. The review of
the literature and clinical cases gives us a wide-angle lens, empirically
supporting our focus on danger in relationships. The school's experience
describes working with a child with undiagnosed autism. The assessments of
attachment both provide information about family members' psychological
strategies for protection from danger and also include the mother's childhood
history of family threat. Their synthesis permits us to construct a developmental
history, from Graeme's mother's childhood history of being triangulated into her
parents' hidden marital discord to it's repetition for Graeme in her own
marriage. New observations included mum's postural/gestural communication to
Graeme and her possible ambivalence about males. Strikingly, Graeme was a case
study (Attachment & Family Therapy, ch. 6) before he was diagnosed with autism.
That presentation focused on Graeme's feeling of rejection by his father. In the
same book, an interpersonal formulation of autism was offered (ch. 3), but it was
not connected to Graeme, showing that when one lacks crucial information, the
clinical formulation is distorted. The crucial information in this case was the
mother's psychological history. Our case suggests that filling the blind spot in
the research on autism with information about family functioning over at least
two generations might change the understanding of autism in ways that could help
families and their children.
PMID- 28693401
TI - Formulating autism systemically: Part 1 - A review of the published literature
and case assessments.
AB - Autism is a psychiatric disorder of unknown aetiology. In this article, the
literature on genetic, neurological, psychological, relational and cultural
causes of autism is reviewed, beginning with the 2014 review of Crittenden,
Dallos, Landini et al. (pp. 64-70) up to and including recent publications in
2017. Some of the findings were unexpected; others led to new questions. The
unexpected findings were the minimal contribution of genes to autism, the
extremely evident neurological differences, the interpersonal quality of the
psychological findings (that lacked evidence of parents' behaviour), the
relational evidence that mothers' childhood trauma, perinatal stress and marital
stress increased the risk of autism, and the reciprocal relation between funding
for treatment of autism and diagnoses of autism. Notably, there was an abundance
of genetic studies, numerous neurological studies and only scattered
psychological, relational and cultural studies, thus rendering those findings
speculative. The new questions included whether mothers used postural/gestural
signs to signal their children to maintain distance and whether mothers
experienced wariness of males as a result of childhood trauma, with their sons
possibly experiencing gender confusion. Following the literature review, a small
archival set of video-recorded and transcribed assessments of attachment of cases
of autism were examined for evidence to corroborate or refute the psychological
and relational findings of the literature review. The findings were striking in
their support of mothers' use of postural/gestural communication regarding
distance, children's close attention to mothers' bodily signals, without looking
at mothers' face, mothers' greater comfort when they approached their sons than
when their sons approached them, one boy's lack of verbal self-representation and
mothers' childhood triangulation. These became hypotheses regarding what to look
for in Part 2 of this article, a prospective, 12-year case study.
PMID- 28693402
TI - Fix my child: The importance of including siblings in clinical assessments.
AB - AIMS: This study examined concordance in the attachment strategies of school-aged
siblings with reference to environmental risk in terms of poverty and
maltreatment. It also investigated the effect of child maltreatment and maternal
mental illness on children's psychosocial functioning in terms of the Dynamic
Maturational Model of Attachment and Adaptation (DMM) including unresolved trauma
and the DMM Depressed modifier. METHODS: The attachment strategies of 30 sibling
pairs, aged 5-14 years, were assessed using the School-age Assessment of
Attachment (SAA). Unlike most previous studies, this study included siblings from
large families of two to six children. RESULTS: The main finding was that as
environmental risk increases, the diversity of sibling attachment strategies
decreases with greater recourse to the DMM Type A3-6 and A/C strategies. Unlike
previous studies, the highest level of concordance was found in sibling pairs
with the opposite gender. Boys whose mothers had a history of mental illness were
significantly more likely than girls to be assessed with the DMM-depression
modifier. CONCLUSION: As danger increases, children in the same family experience
more of the same childhood. Further research should focus on single case, intra
familial studies to build a systemic model of the shared environment. Research
should also evaluate the effects of environmental risk compared with size of the
sibling group on children's attachment strategies. The clinical implications
point to the importance of assessing all children in the family using a model
built around functional formulation rather than diagnosing the symptoms of a
particular child.
PMID- 28693403
TI - Gifts from Mary Ainsworth and John Bowlby.
AB - Attachment theory has developed over many decades - and continues to develop. Its
roots lie in several seminal publications of John Bowlby (the basis of attachment
theory) and Mary D. S. Ainsworth (the notion of individual differences in
attachment). This paper identifies the prescient contributions of these early
publications and two processes (a long-term dialogue and reflection on
discrepancy) that underlay emergent theory. Because I was a student of Ainsworth
when both attachment theory and individual differences in attachment organization
were becoming better known, I offer some of my recollections of that period,
suggesting how that period may have affected current work in attachment.
PMID- 28693404
TI - The association between the behavior rating inventory of executive functioning
and cognitive testing in children diagnosed with a brain tumor.
AB - Pediatric brain tumor survivors (PBTS) suffer from cognitive late effects, such
as deteriorating executive functioning (EF). We explored the suitability of the
Behavior Rating Inventory of Executive Function (BRIEF) to screen for these late
effects. We assessed the relationship between the BRIEF and EF tasks, and between
the BRIEF-Parent and BRIEF-Teacher, and we explored the clinical utility. Eighty
two PBTS (8-18 years) were assessed with EF tasks measuring attention, cognitive
flexibility, inhibition, visual-, and working memory (WM), and with the BRIEF
Parent and BRIEF-Teacher. Pearson's correlations between the BRIEF and EF tasks,
and between the BRIEF-Parent and BRIEF-Teacher were calculated. The BRIEF-Parent
related poorly to EF tasks (rs < .26, ps > .01), but of the BRIEF-Teacher the WM
scale, Monitor-scale, Behavioral-Regulation-Index, and Meta-cognition-Index, and
Total-score (rs > .31, ps < .01) related significantly to some EF tasks. When
controlling for age, only the WM scale and Total score related significantly to
the attention task (ps < .01). The inhibit scales of the BRIEF-Parent and BRIEF
Teacher correlated significantly (r = .33, p < .01). Children with clinically
elevated scores on BRIEF scales that correlated with EF tasks performed worse on
all EF tasks (ds 0.56-1.23, ps < .05). The BRIEF-Teacher Total and Index scores
might better screen general EF in PBTS than the BRIEF-Parent. However, the BRIEF
Teacher is also not specific enough to capture separate EFs. Solely relying on
the BRIEF as a screening measure of EFs in BPTS is insufficient. Questionnaires
and tasks give distinctive, valuable information.
PMID- 28693405
TI - Genetics and immunodysfunction underlying Behcet's disease and immunomodulant
treatment approaches.
AB - Behcet's disease (BD) is a chronic autoimmune condition primarily prevalent in
populations along the Mediterranean Sea. The exact etiology of BD has not been
fully explained yet, but the disease occurrence is associated with a genetic
factor, human leukocyte antigen (HLA)-B51 antigen. Among the various
immunodysfunctions that are found in BD, patients are increased neutrophil
motility and superoxide production, as well as elevated production of tumor
necrosis factor (TNF)-alpha and decreased production of interleukin (IL)-10.
Elevated levels of inflammatory cytokines like IL-1 and IL-17 in BD have been
found associated with aberrant expression of microRNA. Gene polymorphisms in BD
patients have been observed in molecules involved in responses to pathogens that
can ultimately modulate the host antimicrobial response. Moreover, several single
nucleotide polymorphisms (SNPs) have been reported in genes encoding chemokines
and adhesion molecules; many of these changes manifest as increases in vascular
inflammation and vascular damage. Lastly, genetic and epigenetic changes have
been suggested as involved in the pathogenesis of BD. Modifications in DNA
methylation have been found in BD patient monocytes and lymphocytes, leading to
adverse function of these cells. This review presents a comprehensive compilation
of the literature with regard to the immunodysfunction underlying BD, as well as
of the genetics, newly described clinical specifications and novel treatment
strategies using immunomodulants based on the current understanding of BD.
PMID- 28693406
TI - Assessment of the road safety performance of four roundabouts in Kumasi, Ghana.
AB - Upgrade of the Ejisu-Kumasi section of the N6 saw the construction of roundabouts
at selected intersections. Their use appears challenging particularly for
vehicles with elevated Centre-of-Gravity. The objective of this study was to
establish the relative risk of traffic accident deaths or hospitalized injuries
at the roundabouts. Five-year crash data covering a 100 m stretch upstream and
downstream of the roundabouts were analysed. A total of 119 crashes occurred with
18% casualty hospitalization and 12%fatalities. Compared with the Ejisu
roundabout, fatal or hospitalized injuries were significantly higher at the Boadi
(OR = 25.6, p = 0.0021) and Kwame Nkrumah University of Science and Technology
Police Station Junctions (OR = 48.2, p < 0.001). Occupants of buses, heavy goods
vehicles and riders of two wheelers were at elevated risk of deaths or serious
injuries. Crash severity at the round abouts was aggravated by night-time, steep
gradients and adverse cambers. It is recommended that, signalization and grade
separation should be used in the current arrangement where appropriate.
PMID- 28693408
TI - Erratum.
PMID- 28693407
TI - Patterns of drugs prescribed for dental outpatients in Nigeria: findings and
implications.
AB - OBJECTIVES: There are concerns with inappropriate prescribing of medicines among
dentists especially antimicrobials. It is more concerning if this increases
resistance rates. This study aimed to address this by assessing patterns of drugs
prescribed for outpatients attending a hospital dental clinic in Nigeria. The
findings will be used to plan future interventions, particularly around
antimicrobial prescribing, where there are concerns. METHODS AND MATERIALS:
Medical records of patients attending the dental clinic of a leading teaching
hospital in Nigeria were evaluated. Patients referred for admission, without a
prescription, or prescribed medicines without a documented diagnosis were
excluded. RESULTS: Overall, 607 prescriptions were analysed, 314 (51.7%) were for
females. Periodontal and gum diseases (414; 68.1%) were the most frequent
diagnoses, followed by pulpitis (49; 8.2%), and dentoalveolar abscess (43; 7.1%).
A total of 1798 medicines were prescribed for all patients with a mean of 3.0 +/-
0.48 medicines per prescription. Antimicrobials (1178; 65.5%) and analgesics
(620; 34.5%) were the two drug classes prescribed. Ascorbic acid and vitamin B
complex were prescribed for 361 (59.5%) patients. Among antimicrobials,
amoxicillin (564; 95.1%) either alone or combined with clavulanic acid was the
most frequently prescribed, followed by metronidazole (561; 94.6%). Brand name
prescribing was also appreciably higher than WHO recommendations. CONCLUSION:
Polypharmacy, brand name prescriptions, and the frequent prescription of
antimicrobials were common practices at the dental clinic of this teaching
hospital in Nigeria. We suggest a review of the current standard treatment
guidelines in Nigeria to guide dentists on current knowledge- and evidence-based
treatment of common oral diseases.
PMID- 28693409
TI - Long-term outcomes in patients with critical limb ischemia and heart failure with
preserved or reduced ejection fraction.
AB - The impact of heart failure (HF) on long-term survival in patients with critical
limb ischemia (CLI) has not been well described. Outcomes stratified by left
ventricular ejection fraction (EF) are also unknown. A single center
retrospective chart review was performed for patients who underwent treatment for
CLI from 2006 to 2013. Baseline demographics, procedural data and outcomes were
analyzed. HF diagnosis was based on appropriate signs and symptoms as well as
results of non-invasive testing. Among 381 CLI patients, 120 (31%) had a history
of HF and 261 (69%) had no history of heart failure (no-HF). Within the HF group,
74 (62%) had HF with preserved ejection fraction (HFpEF) and 46 (38%) had HF with
reduced ejection fraction (HFrEF). The average EF for those with no-HF, HFpEF and
HFrEF were 59+/-13% vs 56+/-9% vs 30+/-9%, respectively. The likelihood of having
concomitant coronary artery disease (CAD) was lowest in the no-HF group (43%),
higher in the HFpEF group (70%) and highest in the HFrEF group (83%) ( p=0.001).
Five-year survival was on average twofold higher in the no-HF group (43%)
compared to both the HFpEF (19%, p=0.001) and HFrEF groups (24%, p=0.001). Long
term survival rates did not differ between the two HF groups ( p=0.50). There was
no difference in 5-year freedom from major amputation or freedom from major
adverse limb events between the no-HF, HFpEF and HFrEF groups, respectively.
Overall, the combination of CLI and HF is associated with poor 5-year survival,
independent of the degree of left ventricular systolic dysfunction.
PMID- 28693410
TI - Staying married after stroke: a constructivist grounded theory qualitative study.
AB - BACKGROUND: Marriages are one of the most powerful predictors of health and
longevity, yet research in stroke has focused separately on survivors' experience
of impairments and how spouses deal with caregiving. OBJECTIVES: The purpose of
this constructivist grounded theory study was to understand the key themes
related to reconstruction or breakdown of marriages after stroke. METHODS: In
semi-structured interviews, 18 couples in long-term marriages discussed how their
marriages were reconstructed or broke down after one member of the couple
returned home after being hospitalized for a stroke. Constant comparison methods
were used to compare the experiences of 12 couples in which both partners
indicated their relationship was going well with 6 couples who either separated
or remained in parallel marriages. RESULTS: Analysis revealed an overarching
process of reconstructing compatible role-identities and three themes related to
the reconstruction or breakdown of the marital identity: feeling overwhelmed,
resolving conflict, and perceiving value in the marriage. CONCLUSIONS: Our
findings highlight that marriages are contexts in which survivors and spouses can
recalibrate their role-identities. Marriage relationships are not peripheral to
survivors' and spouses' outcomes after stroke; rather, marriage is fundamental to
the management of impairments and to the well-being of the couple.
PMID- 28693411
TI - Corrigendum.
PMID- 28693412
TI - Proteomics-based identification of differentially abundant proteins reveals
adaptation mechanisms of Xanthomonas citri subsp. citri during Citrus sinensis
infection.
AB - BACKGROUND: Xanthomonas citri subsp. citri (Xac) is the causal agent of citrus
canker. A proteomic analysis under in planta infectious and non-infectious
conditions was conducted in order to increase our knowledge about the adaptive
process of Xac during infection. RESULTS: For that, a 2D-based proteomic analysis
of Xac at 1, 3 and 5 days after inoculation, in comparison to Xac growth in NB
media was carried out and followed by MALDI-TOF-TOF identification of 124 unique
differentially abundant proteins. Among them, 79 correspond to up-regulated
proteins in at least one of the three stages of infection. Our results indicate
an important role of proteins related to biofilm synthesis, lipopolysaccharides
biosynthesis, and iron uptake and metabolism as possible modulators of plant
innate immunity, and revealed an intricate network of proteins involved in
reactive oxygen species adaptation during Plants' Oxidative Burst response. We
also identified proteins previously unknown to be involved in Xac-Citrus
interaction, including the hypothetical protein XAC3981. A mutant strain for this
gene has proved to be non-pathogenic in respect to classical symptoms of citrus
canker induced in compatible plants. CONCLUSIONS: This is the first time that a
protein repertoire is shown to be active and working in an integrated manner
during the infection process in a compatible host, pointing to an elaborate
mechanism for adaptation of Xac once inside the plant.
PMID- 28693413
TI - Transcriptome profiling analysis reveals metabolic changes across various growth
phases in Bacillus pumilus BA06.
AB - BACKGROUND: Bacillus pumilus can secret abundant extracellular enzymes, and may
be used as a potential host for the industrial production of enzymes. It is
necessary to understand the metabolic processes during cellular growth. Here, an
RNA-seq based transcriptome analysis was applied to examine B. pumilus BA06
across various growth stages to reveal metabolic changes under two conditions.
RESULTS: Based on the gene expression levels, changes to metabolism pathways that
were specific to various growth phases were enriched by KEGG analysis. Upon entry
into the transition from the exponential growth phase, striking changes were
revealed that included down-regulation of the tricarboxylic acid cycle, oxidative
phosphorylation, flagellar assembly, and chemotaxis signaling. In contrast, the
expression of stress-responding genes was induced when entering the transition
phase, suggesting that the cell may suffer from stress during this growth stage.
As expected, up-regulation of sporulation-related genes was continuous during the
stationary growth phase, which was consistent with the observed sporulation.
However, the expression pattern of the various extracellular proteases was
different, suggesting that the regulatory mechanism may be distinct for various
proteases. In addition, two protein secretion pathways were enriched with genes
responsive to the observed protein secretion in B. pumilus. However, the
expression of some genes that encode sporulation-related proteins and
extracellular proteases was delayed by the addition of gelatin to the minimal
medium. CONCLUSIONS: The transcriptome data depict global alterations in the
genome-wide transcriptome across the various growth phases, which will enable an
understanding of the physiology and phenotype of B. pumilus through gene
expression.
PMID- 28693414
TI - Hypothetical protein Cpn0423 triggers NOD2 activation and contributes to
Chlamydia pneumoniae-mediated inflammation.
AB - BACKGROUND: Chlamydia pneumoniae (C. pneumoniae) is pathogenic to humans, by
causing pulmonary inflammation or bronchitis in both adolescents and young
adults. However, the molecular signals linking C. pneumoniae components to
inflammation remain elusive. This study was to investigate the effect of
Chlamydia-specific Cpn0423 of C. pneumoniae on C. pneumoniae-mediated
inflammation. RESULTS: Cpn0423 was detected outside of C. pneumoniae inclusions,
which induced production of several cytokines including macrophage inflammatory
protein-2 (MIP-2) and interleukins (ILs). Production of the Cpn0423-induced
cytokines was markedly reduced in cells pretreated with NOD2-siRNA, but not with
negative control oligonucleotides. Mice treated with Cpn0423 through intranasal
administration exhibited pulmonary inflammation as evidenced by infiltration of
inflammatory cells, increased inflammatory scores in the lung histology,
recruitment of neutrophils and increased cytokines levels in the BALF.
CONCLUSION: Cpn0423 could be sensed by NOD2, which was identified as an essential
element in a pathway contributing to the development of C. pneumoniae -mediated
inflammation.
PMID- 28693415
TI - Jasmonate-mediated defence responses, unlike salicylate-mediated responses, are
involved in the recovery of grapevine from bois noir disease.
AB - BACKGROUND: Bois noir is an important disease of grapevine (Vitis vinifera L.),
caused by phytoplasmas. An interesting, yet elusive aspect of the bois noir
disease is "recovery", i.e., the spontaneous and unpredictable remission of
symptoms and damage. Because conventional pest management is ineffective against
bois noir, deciphering the molecular bases of recovery is beneficial. The present
study aimed to understand whether salicylate- and jasmonate-defence pathways
might have a role in the recovery from the bois noir disease of grapevine.
RESULTS: Leaves from healthy, bois noir-diseased and bois noir-recovered plants
were compared, both in the presence (late summer) and absence (late spring) of
bois noir symptoms on the diseased plants. Analyses of salicylate and jasmonate
contents, as well as the expression of genes involved in their biosynthesis,
signalling and action, were evaluated. In symptomatic diseased plants (late
summer), unlike symptomless plants (late spring), salicylate biosynthesis was
increased and salicylate-responsive genes were activated. In contrast, jasmonate
biosynthesis and signalling genes were up-regulated both in recovered and
diseased plants at all sampling dates. The activation of salicylate signalling in
symptomatic plants might have antagonised the jasmonate-mediated defence response
by suppressing the expression of jasmonate-responsive genes. CONCLUSIONS: Our
results suggest that grapevine reacts to phytoplasma infection through salicylate
mediated signalling, although the resultant full activation of a salicylate
mediated response is apparently ineffective in conferring resistance against bois
noir disease. Activation of the salicylate signalling pathway that is associated
with the presence of bois noir phytoplasma seems to antagonise the jasmonate
defence response, by failing to activate or suppressing both the expression of
some jasmonate responsive genes that act downstream of the jasmonate biosynthetic
pathway, as well as the first events of the jasmonate signalling pathway. On the
other hand, activation of the entire jasmonate signalling pathway in recovered
plants suggests the potential importance of jasmonate-regulated defences in
preventing bois noir phytoplasma infections and the subsequent development of
bois noir disease. Thus, on one hand, recovery could be achieved and maintained
over time by preventing the activation of defence genes associated with
salicylate signalling, and on the other hand, by activating jasmonate signalling
and other defence responses.
PMID- 28693416
TI - Whole-transcriptome analysis delineates the human placenta gene network and its
associations with fetal growth.
AB - BACKGROUND: The placenta is the principal organ regulating intrauterine growth
and development, performing critical functions on behalf of the developing fetus.
The delineation of functional networks and pathways driving placental processes
has the potential to provide key insight into intrauterine perturbations that
result in adverse birth as well as later life health outcomes. RESULTS: We
generated the transcriptome-wide profile of 200 term human placenta using the
Illumina HiSeq 2500 platform and characterized the functional placental gene
network using weighted gene coexpression network analysis (WGCNA). We identified
17 placental coexpression network modules that were dominated by functional
processes including growth, organ development, gas exchange and immune response.
Five network modules, enriched for processes including cellular respiration,
amino acid transport, hormone signaling, histone modifications and gene
expression, were associated with birth weight; hub genes of all five modules
(CREB3, DDX3X, DNAJC14, GRHL1 and C21orf91) were significantly associated with
fetal growth restriction, and one hub gene (CREB3) was additionally associated
with fetal overgrowth. CONCLUSIONS: In this largest RNA-Seq based transcriptome
wide profiling study of human term placenta conducted to date, we delineated a
placental gene network with functional relevance to fetal growth using a network
based approach with superior scale reduction capacity. Our study findings not
only implicate potential molecular mechanisms underlying fetal growth but also
provide a reference placenta gene network to inform future studies investigating
placental dysfunction as a route to future disease endpoints.
PMID- 28693417
TI - ACE: an efficient and sensitive tool to detect insecticide resistance-associated
mutations in insect acetylcholinesterase from RNA-Seq data.
AB - BACKGROUND: Insecticide resistance is a substantial problem in controlling
agricultural and medical pests. Detecting target site mutations is crucial to
manage insecticide resistance. Though PCR-based methods have been widely used in
this field, they are time-consuming and inefficient, and typically have a high
false positive rate. Acetylcholinesterases (Ace) is the neural target of the
widely used organophosphate (OP) and carbamate insecticides. However, there is
not any software available to detect insecticide resistance associated mutations
in RNA-Seq data at present. RESULTS: A computational pipeline ACE was developed
to detect resistance mutations of ace in insect RNA-Seq data. Known ace
resistance mutations were collected and used as a reference. We constructed a Web
server for ACE, and the standalone software in both Linux and Windows versions is
available for download. ACE was used to analyse 971 RNA-Seq data from 136 studies
in 7 insect pests. The mutation frequency of each RNA-Seq dataset was calculated.
The results indicated that the resistance frequency was 30%-44% in an eastern
Ugandan Anopheles population, thus suggesting this resistance-conferring mutation
has reached high frequency in these mosquitoes in Uganda. Analyses of RNA-Seq
data from the diamondback moth Plutella xylostella indicated that the G227A
mutation was positively related with resistance levels to organophosphate or
carbamate insecticides. The wasp Nasonia vitripennis had a low frequency of
resistant reads (<5%), but the agricultural pests Chilo suppressalis and Bemisia
tabaci had a high resistance frequency. All ace reads in the 30 B. tabaci RNA-Seq
data were resistant reads, suggesting that insecticide resistance has spread to
very high frequency in B. tabaci. CONCLUSIONS: To the best of our knowledge, the
ACE pipeline is the first tool to detect resistance mutations from RNA-Seq data,
and it facilitates the full utilization of large-scale genetic data obtained by
using next-generation sequencing.
PMID- 28693418
TI - Phylogenetic conservatism in skulls and evolutionary lability in limbs -
morphological evolution across an ancient frog radiation is shaped by diet,
locomotion and burrowing.
AB - BACKGROUND: Quantifying morphological diversity across taxa can provide valuable
insight into evolutionary processes, yet its complexities can make it difficult
to identify appropriate units for evaluation. One of the challenges in this field
is identifying the processes that drive morphological evolution, especially when
accounting for shape diversification across multiple structures. Differential
levels of co-varying phenotypic diversification can conceal selective pressures
on traits due to morphological integration or modular shape evolution of
different structures, where morphological evolution of different modules is
explained either by co-variation between them or by independent evolution,
respectively. METHODS: Here we used a 3D geometric morphometric approach with x
ray micro CT scan data of the skull and bones of forelimbs and hindlimbs of
representative species from all 21 genera of the ancient Australo-Papuan
myobatrachid frogs and analysed their shape both as a set of distinct modules and
as a multi-modular integrative structure. We then tested three main questions:
(i) are evolutionary patterns and the amount and direction of morphological
changes similar in different structures and subfamilies?, (ii) do skulls and
limbs show different levels of integration?, and (iii) is morphological diversity
of skulls and limbs shaped by diet, locomotion, burrowing behavior, and ecology?.
RESULTS: Our results in both skulls and limbs support a complex evolutionary
pattern typical of an adaptive radiation with an early burst of phenotypic
variation followed by slower rates of morphological change. Skull shape diversity
was phylogenetically conserved and correlated with diet whereas limb shape was
more labile and associated with diet, locomotion, and burrowing behaviour.
Morphological changes between different limb bones were highly correlated,
depicting high morphological integration. In contrast, overall limb and skull
shape displayed semi-independence in morphological evolution, indicating
modularity. CONCLUSIONS: Our results illustrate how morphological diversification
in animal clades can follow complex processes, entailing selective pressures from
the environment as well as multiple trait covariance with varying degrees of
independence across different structures. We suggest that accurately quantifying
shape diversity across multiple structures is crucial in order to understand
complex evolutionary processes.
PMID- 28693419
TI - De novo transcriptomic analysis of cowpea (Vigna unguiculata L. Walp.) for genic
SSR marker development.
AB - BACKGROUND: Cowpea [Vigna unguiculata (L.) Walp.] is one of the most important
legumes in tropical and semi-arid regions. However, there is relatively little
genomic information available for genetic research on and breeding of cowpea. The
objectives of this study were to analyse the cowpea transcriptome and develop
genic molecular markers for future genetic studies of this genus. RESULTS:
Approximately 54 million high-quality cDNA sequence reads were obtained from
cowpea based on Illumina paired-end sequencing technology and were de novo
assembled to generate 47,899 unigenes with an N50 length of 1534 bp. Sequence
similarity analysis revealed 36,289 unigenes (75.8%) with significant similarity
to known proteins in the non-redundant (Nr) protein database, 23,471 unigenes
(49.0%) with BLAST hits in the Swiss-Prot database, and 20,654 unigenes (43.1%)
with high similarity in the Kyoto Encyclopedia of Genes and Genomes (KEGG)
database. Further analysis identified 5560 simple sequence repeats (SSRs) as
potential genic molecular markers. Validating a random set of 500 SSR markers
yielded 54 polymorphic markers among 32 cowpea accessions. CONCLUSIONS: This
transcriptomic analysis of cowpea provided a valuable set of genomic data for
characterizing genes with important agronomic traits in Vigna unguiculata and a
new set of genic SSR markers for further genetic studies and breeding in cowpea
and related Vigna species.
PMID- 28693420
TI - Differential proteomic analysis of replanted Rehmannia glutinosa roots by iTRAQ
reveals molecular mechanisms for formation of replant disease.
AB - BACKGROUND: The normal growth of Rehmannia glutinosa, a widely used medicinal
plant in China, is severely disturbed by replant disease. The formation of
replant disease commonly involves interactions among plants, allelochemicals and
microbes; however, these relationships remain largely unclear. As a result, no
effective measures are currently available to treat replant disease. RESULTS: In
this study, an integrated R. glutinosa transcriptome was constructed, from which
an R. glutinosa protein library was obtained. iTRAQ technology was then used to
investigate changes in the proteins in replanted R. glutinosa roots, and the
proteins that were expressed in response to replant disease were identified. An
integrated R. glutinosa transcriptome from different developmental stages of
replanted and normal-growth R. glutinosa produced 65,659 transcripts, which were
accurately translated into 47,818 proteins. Using this resource, a set of 189
proteins was found to be significantly differentially expressed between normal
growth and replanted R. glutinosa. Of the proteins that were significantly
upregulated in replanted R. glutinosa, most were related to metabolism, immune
responses, ROS generation, programmed cell death, ER stress, and lignin
synthesis. CONCLUSIONS: By integrating these key events and the results of
previous studies on replant disease formation, a new picture of the damaging
mechanisms that cause replant disease stress emerged. Replant disease altered the
metabolic balance of R. glutinosa, activated immune defence systems, increased
levels of ROS and antioxidant enzymes, and initiated the processes of cell death
and senescence in replanted R. glutinosa. Additionally, lignin deposition in R.
glutinosa roots that was caused by replanting significantly inhibited tuberous
root formation. These key processes provide important insights into the
underlying mechanisms leading to the formation of replant disease and also for
the subsequent development of new control measures to improve production and
quality of replanted plants.
PMID- 28693421
TI - LipidMatch: an automated workflow for rule-based lipid identification using
untargeted high-resolution tandem mass spectrometry data.
AB - BACKGROUND: Lipids are ubiquitous and serve numerous biological functions; thus
lipids have been shown to have great potential as candidates for elucidating
biomarkers and pathway perturbations associated with disease. Methods expanding
coverage of the lipidome increase the likelihood of biomarker discovery and could
lead to more comprehensive understanding of disease etiology. RESULTS: We
introduce LipidMatch, an R-based tool for lipid identification for liquid
chromatography tandem mass spectrometry workflows. LipidMatch currently has over
250,000 lipid species spanning 56 lipid types contained in in silico
fragmentation libraries. Unique fragmentation libraries, compared to other open
source software, include oxidized lipids, bile acids, sphingosines, and
previously uncharacterized adducts, including ammoniated cardiolipins. LipidMatch
uses rule-based identification. For each lipid type, the user can select which
fragments must be observed for identification. Rule-based identification allows
for correct annotation of lipids based on the fragments observed, unlike typical
identification based solely on spectral similarity scores, where over-reporting
structural details that are not conferred by fragmentation data is common.
Another unique feature of LipidMatch is ranking lipid identifications for a given
feature by the sum of fragment intensities. For each lipid candidate, the
intensities of experimental fragments with exact mass matches to expected in
silico fragments are summed. The lipid identifications with the greatest summed
intensity using this ranking algorithm were comparable to other lipid
identification software annotations, MS-DIAL and Greazy. For example, for
features with identifications from all 3 software, 92% of LipidMatch
identifications by fatty acyl constituents were corroborated by at least one
other software in positive mode and 98% in negative ion mode. CONCLUSIONS:
LipidMatch allows users to annotate lipids across a wide range of high resolution
tandem mass spectrometry experiments, including imaging experiments, direct
infusion experiments, and experiments employing liquid chromatography. LipidMatch
leverages the most extensive in silico fragmentation libraries of freely
available software. When integrated into a larger lipidomics workflow, LipidMatch
may increase the probability of finding lipid-based biomarkers and determining
etiology of disease by covering a greater portion of the lipidome and using
annotation which does not over-report biologically relevant structural details of
identified lipid molecules.
PMID- 28693422
TI - Relationships between drought, heat and air humidity responses revealed by
transcriptome-metabolome co-analysis.
AB - BACKGROUND: Elevated temperature and reduced water availability are frequently
linked abiotic stresses that may provoke distinct as well as interacting
molecular responses. Based on non-targeted metabolomic and transcriptomic
measurements from Arabidopsis rosettes, this study aims at a systematic
elucidation of relevant components in different drought and heat scenarios as
well as relationships between molecular players of stress response. RESULTS: In
combined drought-heat stress, the majority of single stress responses are
maintained. However, interaction effects between drought and heat can be
discovered as well; these relate to protein folding, flavonoid biosynthesis and
growth inhibition, which are enhanced, reduced or specifically induced in
combined stress, respectively. Heat stress experiments with and without
supplementation of air humidity for maintenance of vapor pressure deficit suggest
that decreased relative air humidity due to elevated temperature is an important
component of heat stress, specifically being responsible for hormone-related
responses to water deprivation. Remarkably, this "dry air effect" is the primary
trigger of the metabolomic response to heat. In contrast, the transcriptomic
response has a substantial temperature component exceeding the dry air component
and including up-regulation of many transcription factors and protein folding
related genes. Data level integration independent of prior knowledge on pathways
and condition labels reveals shared drought and heat responses between
transcriptome and metabolome, biomarker candidates and co-regulation between
genes and metabolic compounds, suggesting novel players in abiotic stress
response pathways. CONCLUSIONS: Drought and heat stress interact both at
transcript and at metabolite response level. A comprehensive, non-targeted view
of this interaction as well as non-interacting processes is important to be taken
into account when improving tolerance to abiotic stresses in breeding programs.
Transcriptome and metabolome may respond with different extent to individual
stress components. Their contrasting behavior in response to temperature stress
highlights that the protein folding machinery effectively shields the metabolism
from stress. Disentangling the complex relationships between transcriptome and
metabolome in response to stress is an enormous challenge. As demonstrated by
case studies with supporting evidence from additional data, the large dataset
provided in this study may assist in determining linked genetic and metabolic
features as candidates for future mechanistic analyses.
PMID- 28693423
TI - Indole-3-butyric acid promotes adventitious rooting in Arabidopsis thaliana thin
cell layers by conversion into indole-3-acetic acid and stimulation of
anthranilate synthase activity.
AB - BACKGROUND: Indole-3-acetic acid (IAA), and its precursor indole-3-butyric acid
(IBA), control adventitious root (AR) formation in planta. Adventitious roots are
also crucial for propagation via cuttings. However, IBA role(s) is/are still far
to be elucidated. In Arabidopsis thaliana stem cuttings, 10 MUM IBA is more AR
inductive than 10 MUM IAA, and, in thin cell layers (TCLs), IBA induces ARs when
combined with 0.1 MUM kinetin (Kin). It is unknown whether arabidopsis TCLs
produce ARs under IBA alone (10 MUM) or IAA alone (10 MUM), and whether they
contain endogenous IAA/IBA at culture onset, possibly interfering with the
exogenous IBA/IAA input. Moreover, it is unknown whether an IBA-to-IAA conversion
is active in TCLs, and positively affects AR formation, possibly through the
activity of the nitric oxide (NO) deriving from the conversion process. RESULTS:
Revealed undetectable levels of both auxins at culture onset, showing that
arabidopsis TCLs were optimal for investigating AR-formation under the total
control of exogenous auxins. The AR-response of TCLs from various ecotypes,
transgenic lines and knockout mutants was analyzed under different treatments. It
was shown that ARs are better induced by IBA than IAA and IBA + Kin. IBA induced
IAA-efflux (PIN1) and IAA-influx (AUX1/LAX3) genes, IAA-influx carriers
activities, and expression of ANTHRANILATE SYNTHASE -alpha1 (ASA1), a gene
involved in IAA-biosynthesis. ASA1 and ANTHRANILATE SYNTHASE -beta1 (ASB1), the
other subunit of the same enzyme, positively affected AR-formation in the
presence of exogenous IBA, because the AR-response in the TCLs of their mutant
wei2wei7 was highly reduced. The AR-response of IBA-treated TCLs from ech2ibr10
mutant, blocked into IBA-to-IAA-conversion, was also strongly reduced. Nitric
oxide, an IAA downstream signal and a by-product of IBA-to-IAA conversion, was
early detected in IAA- and IBA-treated TCLs, but at higher levels in the latter
explants. CONCLUSIONS: Altogether, results showed that IBA induced AR-formation
by conversion into IAA involving NO activity, and by a positive action on IAA
transport and ASA1/ASB1-mediated IAA-biosynthesis. Results are important for
applications aimed to overcome rooting recalcitrance in species of economic
value, but mainly for helping to understand IBA involvement in the natural
process of adventitious rooting.
PMID- 28693424
TI - Bacillus subtilis IolQ (DegA) is a transcriptional repressor of iolX encoding
NAD+-dependent scyllo-inositol dehydrogenase.
AB - BACKGROUND: Bacillus subtilis is able to utilize at least three inositol
stereoisomers as carbon sources, myo-, scyllo-, and D-chiro-inositol (MI, SI, and
DCI, respectively). NAD+-dependent SI dehydrogenase responsible for SI catabolism
is encoded by iolX. Even in the absence of functional iolX, the presence of SI or
MI in the growth medium was found to induce the transcription of iolX through an
unknown mechanism. RESULTS: Immediately upstream of iolX, there is an operon that
encodes two genes, yisR and iolQ (formerly known as degA), each of which could
encode a transcriptional regulator. Here we performed an inactivation analysis of
yisR and iolQ and found that iolQ encodes a repressor of the iolX transcription.
The coding sequence of iolQ was expressed in Escherichia coli and the gene
product was purified as a His-tagged fusion protein, which bound to two sites
within the iolX promoter region in vitro. CONCLUSIONS: IolQ is a transcriptional
repressor of iolX. Genetic evidences allowed us to speculate that SI and MI might
possibly be the intracellular inducers, however they failed to antagonize DNA
binding of IolQ in in vitro experiments.
PMID- 28693425
TI - Cyclic PaO2 oscillations assessed in the renal microcirculation: correlation with
tidal volume in a porcine model of lung lavage.
AB - BACKGROUND: Oscillations of the arterial partial pressure of oxygen induced by
varying shunt fractions occur during cyclic alveolar recruitment within the
injured lung. Recently, these were proposed as a pathomechanism that may be
relevant for remote organ injury following acute respiratory distress syndrome.
This study examines the transmission of oxygen oscillations to the renal tissue
and their tidal volume dependency. METHODS: Lung injury was induced by repetitive
bronchoalveolar lavage in eight anaesthetized pigs. Cyclic alveolar recruitment
was provoked by high tidal volume ventilation. Oscillations of the arterial
partial pressure of oxygen were measured in real-time in the macrocirculation by
multi-frequency phase fluorimetry and in the renal microcirculation by combined
white-light spectrometry and laser-Doppler flowmetry during tidal volume down
titration. RESULTS: Significant respiratory-dependent oxygen oscillations were
detected in the macrocirculation and transmitted to the renal microcirculation in
a substantial extent. The amplitudes of these oscillations significantly
correlate to the applied tidal volume and are minimized during down-titration.
CONCLUSIONS: In a porcine model oscillations of the arterial partial pressure of
oxygen are induced by cyclic alveolar recruitment and transmitted to the renal
microcirculation in a tidal volume-dependent fashion. They might play a role in
organ crosstalk and remote organ damage following lung injury.
PMID- 28693426
TI - Evolution, gene expression profiling and 3D modeling of CSLD proteins in cotton.
AB - BACKGROUND: Among CESA-like gene superfamily, the cellulose synthase-like D
(CSLD) genes are most similar to cellulose synthase genes and have been reported
to be involved in tip-growing cell and stem development. However, there has been
no genome-wide characterization of this gene subfamily in cotton. We thus sought
to analyze the evolution and functional characterization of CSLD proteins in
cotton based on fully sequenced cotton genomes. RESULTS: A total of 23 full
length CSLD proteins were identified in Gossypium raimondii, Gossypium arboreum
and Gossypium hirsutum. The phylogenetic tree divided the CSLD proteins into five
clades with strong support: CSLD1, CSLD2/3, CSLD4, CSLD5 and CSLD6. The total
expression of GhCSLD genes was the highest in androecium & gynoecium (mostly
contributed by CSLD1 and CSLD4) compared with other CSL genes. CSLD1 and CSLD4
were only highly expressed in androecium & gynoecium (A&G), and showed tissue
specific expression. The total expression of CSLD2/3, 5 and 6 was highest in the
specific tissues. These results suggest that CSLD genes showed the different
pattern of expression. Cotton CSLD proteins were subjected to different
evolutionary pressures, and the CSLD1 and CSLD4 proteins exhibited episodic and
long-term shift positive selection. The predicted three-dimensional structure of
GrCSLD1 suggested that GrCSLD1 belongs to glycosyltransferase family 2. The amino
acid residues under positive selection in the CSLD1 lineage are positioned in a
region adjacent to the class-specific region (CSR), beta1-strand and
transmembrane helices (TMHs) in the GrCSLD1structure. CONCLUSION: Our results
characterized the CSLD proteins by an integrated approach containing phylogeny,
transcriptional profiling and 3D modeling. The study added to the understanding
about the importance of the CSLD family and provide a useful reference for
selecting candidate genes and their associations with the biosynthesis of the
cell wall in cotton.
PMID- 28693427
TI - Selection bias and subject refusal in a cluster-randomized controlled trial.
AB - BACKGROUND: Selection bias and non-participation bias are major methodological
concerns which impact external validity. Cluster-randomized controlled trials are
especially prone to selection bias as it is impractical to blind clusters to
their allocation into intervention or control. This study assessed the impact of
selection bias in a large cluster-randomized controlled trial. METHODS: The
Improved Cardiovascular Risk Reduction to Enhance Rural Primary Care (ICARE)
study examined the impact of a remote pharmacist-led intervention in twelve
medical offices. To assess eligibility, a standardized form containing patient
demographics and medical information was completed for each screened patient.
Eligible patients were approached by the study coordinator for recruitment. Both
the study coordinator and the patient were aware of the site's allocation prior
to consent. Patients who consented or declined to participate were compared
across control and intervention arms for differing characteristics. Statistical
significance was determined using a two-tailed, equal variance t-test and a chi
square test with adjusted Bonferroni p-values. Results were adjusted for random
cluster variation. RESULTS: There were 2749 completed screening forms returned to
research staff with 461 subjects who had either consented or declined
participation. Patients with poorly controlled diabetes were found to be
significantly more likely to decline participation in intervention sites compared
to those in control sites. A higher mean diastolic blood pressure was seen in
patients with uncontrolled hypertension who declined in the control sites
compared to those who declined in the intervention sites. However, these findings
were no longer significant after adjustment for random variation among the sites.
After this adjustment, females were now found to be significantly more likely to
consent than males (odds ratio = 1.41; 95% confidence interval = 1.03, 1.92).
CONCLUSIONS: Though there appeared to be a higher consent rate for females than
for males, the overall impact of potential selection bias and refusal to
participate was minimal. Without rigorous methodology, selection bias may be a
threat to external validity in cluster-randomized trials. TRIAL REGISTRATION:
NCT01983813 . Date of registration: Oct. 28, 2013.
PMID- 28693428
TI - Inverse probability of treatment-weighted competing risks analysis: an
application on long-term risk of urinary adverse events after prostate cancer
treatments.
AB - BACKGROUND: To illustrate the 10-year risks of urinary adverse events (UAEs)
among men diagnosed with prostate cancer and treated with different types of
therapy, accounting for the competing risk of death. METHODS: Prostate cancer is
the second most common malignancy among adult males in the United States. Few
studies have reported the long-term post-treatment risk of UAEs and those that
have, have not appropriately accounted for competing deaths. This paper conducts
an inverse probability of treatment (IPT) weighted competing risks analysis to
estimate the effects of different prostate cancer treatments on the risk of UAE,
using a matched-cohort of prostate cancer/non-cancer control patients from the
Surveillance, Epidemiology and End Results (SEER) Medicare database. RESULTS:
Study dataset included men age 66 years or older that are 83% white and had a
median follow-up time of 4.14 years. Patients that underwent combination radical
prostatectomy and external beam radiotherapy experienced the highest risk of UAE
(IPT-weighted competing risks: HR 3.65 with 95% CI (3.28, 4.07); 10-yr.
cumulative incidence = 36.5%). CONCLUSIONS: Findings suggest that IPT-weighted
competing risks analysis provides an accurate estimator of the cumulative
incidence of UAE taking into account the competing deaths as well as measured
confounding bias.
PMID- 28693429
TI - Plasma homocysteine levels associated with a corrected QT interval.
AB - BACKGROUND: Little is known about the relationship between homocysteine (Hcy)
levels and the QT interval. We examined the association of different Hcy levels
with corrected QT (QTc) intervals in a general population. METHODS: Plasma levels
of Hcy were assessed in a population-based study of 7002 participants 35 years of
age and older from 2012 to 2013. Twelve-lead ECGs were performed on all
participants and analyzed automatically. RESULTS: The distribution of Hcy levels
was determined for an entire population after the data were grouped into
quartiles (Q1: <=11.1umol/L; Q2: 11.1-13.8umol/L; Q3: 13.8-18.2 umol/L; Q4 > 18.2
umol/L). The mean value of the QTc interval in each quartile was 433.2 +/- 23.8
ms, 430.0 +/- 24.6 ms, 429.2 +/- 24.5 ms and 430.6 +/- 25.7 ms. Multiple logistic
regression analyses showed that, compared with the second quartile, and after
fully adjusting for potential confounding factors, the odds for QTc > 440 ms in
the first and fourth quartile increased (P < 0.05), (OR: 1.23, 95% CI: 1.05-1.43
for Q1; OR: 1.40, 95% CI: 1.19-1.65 for Q4). CONCLUSIONS: QTc interval was
associated with the Hcy level in this general population.
PMID- 28693430
TI - Risk factors for coronary artery disease in patients undergoing elective coronary
angiography in Jordan.
AB - BACKGROUND: Unhealthy lifestyle factors such as smoking, obesity, inactivity and
type 2 diabetes are endemic in the Middle East. The public health consequences
might be detrimental; however, local studies on risk factors for coronary artery
disease (CAD) are scarce. METHODS: Patients referred for coronary angiography at
a tertiary hospital in Amman, Jordan, between January and December 2015, were
included in this study. Risk factors for CAD were assessed in a multivariate
logistic regression model, and presented as odds ratio (OR) with 95% confidence
interval (CI). RESULTS: Among 557 participants, 356 (63.9%) had CAD and 201
(36.1%) had a normal cardiogram. The majority (n = 395, 70.9%) were male, and
median age was 55 years (interquartile range 47-64). Two-hundred-and-fifteen
(38.6%) individuals reported previous diabetes, and 287 (51.5%) were current or
previous smokers. In multivariate analysis, male gender (OR 3.7, 95% CI 2.3-6.0),
age (45-54 years: OR 4.8, 95% CI 2.7-8.5; 55-64 years: OR 6.0, 95% CI 3.2-11.4;
>=65 years: OR 15.7, 95% CI 7.8-31.3), previous diabetes (OR 2.6, 95% CI 1.7-4.1)
and current/previous smoking (OR 2.1, 95% CI 1.3-3.4) were significant predictors
of CAD. CONCLUSIONS: Age, gender, diabetes and smoking were strong and
significant risk factors for CAD in Jordan. Public health interventions to reduce
the prevalence of smoking and diabetes are urgently needed.
PMID- 28693431
TI - The attenuation of renal fibrosis by histone deacetylase inhibitors is associated
with the plasticity of FOXP3+IL-17+ T cells.
AB - BACKGROUND: The histone deacetylase (HDAC) inhibitor, which has potential effects
on epigenetic modifications, had been reported to attenuate renal fibrosis. CD4+
forkhead box P3 (FOXP3)+ T regulatory (Treg) cells may be converted to
inflammation-associated T helper 17 cells (Th17) with tissue fibrosis properties.
The association between FOXP3+IL-17+ T cells and the attenuation of renal
fibrosis by the HDAC inhibitor is not clear. METHODS: This study evaluated the
roles of the HDAC inhibitor, Treg cells and their differentiation into Th17
cells, which aggravate chronic inflammation and renal fibrosis in a unilateral
ureteral obstruction (UUO) mouse model. The study groups included control and UUO
mice that were monitored for 7, 14 or 21 days. RESULTS: Juxtaglomerular (JG)
hyperplasia, angiotensin II type 1 receptor (AT1R) expression and lymphocyte
infiltration were observed in renal tissues after UUO but were decreased after
trichostatin A (TSA) treatment, a HDAC inhibitor. The number of CD4+FOXP3+ T
cells increased progressively, along with the number of FOXP3+interleukin (IL)
17+ T cells, after 14 days, and their numbers then progressively decreased with
increasing CD4+IL-17+ T cell numbers, as demonstrated by double
immunohistochemistry. Progressive renal fibrosis was associated with the loss of
CD4+FOXP3+IL-17+ T cells in splenic single-cell suspensions. FOXP3+IL-17+ T cells
expressed TGF-beta1 both in vitro and in vivo, and TGF-beta1 expression was
significantly knockdown by IL-17 siRNA in vitro. These cells were found to play a
role in converting Tregs into IL-17- and TGF-beta1-producing cells. CONCLUSIONS:
TSA treatment decreased JG hyperplasia, the percentage of FOXP3+IL-17+ cells and
the degree of fibrosis, suggesting that therapeutic benefits may result from
epigenetic modifications.
PMID- 28693432
TI - Seroprevalence and risk factors of Toxoplasma gondii infection in pregnant women
from Bobo Dioulasso, Burkina Faso.
AB - BACKGROUND: Toxoplasmosis is one of the common worldwide parasitic zoonosis due
to Toxoplasma gondii (T. gondii). Toxoplasmosis during pregnancy can result in
fetal and neonatal death or various congenital defects. The aim of this study was
to assess the seroprevalence and risk factors of T. gondii infection in pregnant
women following antenatal care (ANC) services at Bobo Dioulasso. METHODS: A cross
sectional study was conducted enrolling a sample of 316 pregnant women attending
ANC at centers for maternal and child health of Bobo-Dioulasso town from March
2013 to February 2014. Data on socio-demographic and potential risk factors were
collected from each study participant using structured questionnaire through face
to-face interview. Moreover, venous blood specimens were collected and tested for
IgM and IgG anti-T. gondii antibodies by enzyme-linked immunosorbent assay and
enzyme linked fluorescent assay, respectively. Multivariable logistic regression
modeling was used to identify the potential predictor variables for T. gondii
infection. RESULTS: The overall seroprevalence for T. gondii infection was 31.1%
(98/316). All the pregnant women were positive for IgG anti-bodies exclusively.
Multivariable logistic regression analysis showed that having at least a
secondary education level (AOR = 2.23; 95% CI: [1.04-4.63]); being urban resident
(AOR = 2.81; 95% CI: [1.24-6.86]) and the consumption of meat combination (pork +
beef + mutton + wild meat + poultry) (AOR = 4.00; 95% CI: [1.06-15.24]) were
potential risk factors of T. gondii infection. CONCLUSION: Toxoplasmosis is
frequent in pregnant women and studies that show incidence of T. gondii among the
neonates have to be done to introduce routine antenatal screening program to
control congenital toxoplasmosis. There is the need for preventive measures such
as education of pregnant women about the transmission routes and prevention
methods of toxoplasmosis at ANC clinics.
PMID- 28693433
TI - Prospective evaluation of computer-assisted analysis of skeletal lesions for the
staging of prostate cancer.
AB - BACKGROUND: The purpose of this study was to compare the agreement of the bone
scan index (BSI) using EXINI BoneBSI versus experts' readings in the initial
staging for bone metastasis in prostate cancer. In addition, the diagnostic
outcome was assessed in a large subset of patients where a true reference for
metastases could be determined based on clinical and biochemical follow-up and/or
supplementary imaging. METHODS: A total of 342 patients had a bone scintigraphy
as part of routine staging for prostate cancer. Supplementary imaging was
obtained at the discretion of the referring urologist. After full recruitment,
the BSI and the number of malignant lesions were calculated using EXINI BoneBSI,
and three imaging experts independently classified bone status by a dichotomous
outcome (M1 for bone metastasis, M0 for no bone metastasis). A true reference was
available in a subset of the patients based on post-operative prostate-specific
antigen responses after radical prostatectomy and/or supplementary imaging.
RESULTS: Software analysis with a BSI > 0 as the cut-off for metastasis showed
excellent agreement with expert classification for M1 disease (96% of the
patients) but modest agreement for M0 disease (38%). With a BSI > 1, the
agreement was 58% for M1 and 98% for M0. Software analyses based on individual
European Association of Urology risk classification did not improve the
diagnostic performance. Among patients with a true reference, the software showed
metastasis in 64% of the M0 patients but correctly classified metastases in all
M1 patients. The sensitivity was 100%, the specificity was 36%, the positive
predictive value was 12.6% and the negative predictive value was 100% with a BSI
>0 compared with 66.7%, 97.8%, 72.7%, and 97.0% with a BSI > 1. CONCLUSION: The
diagnostic value of using EXINI Bone for the BSI in the staging of newly
diagnosed prostate cancer is limited.
PMID- 28693434
TI - Symptom burden in chronic kidney disease; a population based cross sectional
study.
AB - BACKGROUND: Physical and psychological symptoms are among main manifestations of
Chronic Kidney Disease (CKD). This study aimed to assess the symptom burden and
self-perceived severity of symptoms among CKD patients living in a district in
Sri Lanka. METHOD: A community based cross-sectional study included a sample of
randomly selected 1174 CKD patients from all 19 Medical Officer of Health areas
in the district of Anuradhapura. Trained para-medical staff visited the
households and administered the locally validated questionnaire to assess the
presence and severity of symptoms. The inquiry was on 25 symptoms in a 5 point
Likert scale indicating the severity during the previous week. Symptom burden
score was constructed by summing each symptom severity score which ranged from 0
to 125. RESULTS: A total of 1118 CKD patients participated with a response rate
of 95.2%. The mean age was 58.3 (SD 10.8) years and 62.7% were males. A majority
were in CKD stage 4 (58.3%). Bone/joint pain was the most experienced symptom
(87.6%; 95%CI 85.6-89.5). Loss of libido was the most severe symptom. The median
symptom burden score was 35.0 (IQR 20.0-50.0). Multiple linear regression
revealed education up to Advanced Level (beta -9.176), CKD stage V (beta 3.373),
being dialyzed (beta 20.944), comorbidities (beta 4.241) and being employed (beta
-9.176) to be significant predictors of symptom burden. CONCLUSIONS: Patients in
all stages of CKD experience high symptom burden warranting rigorous measures to
relieve symptoms and to improve the well-being of CKD patients.
PMID- 28693435
TI - Data cleaning and management protocols for linked perinatal research data: a good
practice example from the Smoking MUMS (Maternal Use of Medications and Safety)
Study.
AB - BACKGROUND: Data cleaning is an important quality assurance in data linkage
research studies. This paper presents the data cleaning and preparation process
for a large-scale cross-jurisdictional Australian study (the Smoking MUMS Study)
to evaluate the utilisation and safety of smoking cessation pharmacotherapies
during pregnancy. METHODS: Perinatal records for all deliveries (2003-2012) in
the States of New South Wales (NSW) and Western Australia were linked to State
based data collections including hospital separation, emergency department and
death data (mothers and babies) and congenital defect notifications (babies in
NSW) by State-based data linkage units. A national data linkage unit linked
pharmaceutical dispensing data for the mothers. All linkages were probabilistic.
Twenty two steps assessed the uniqueness of records and consistency of items
within and across data sources, resolved discrepancies in the linkages between
units, and identified women having records in both States. RESULTS: State-based
linkages yielded a cohort of 783,471 mothers and 1,232,440 babies. Likely false
positive links relating to 3703 mothers were identified. Corrections of baby's
date of birth and age, and parity were made for 43,578 records while 1996 records
were flagged as duplicates. Checks for the uniqueness of the matches between
State and national linkages detected 3404 ID clusters, suggestive of missed links
in the State linkages, and identified 1986 women who had records in both States.
CONCLUSIONS: Analysis of content data can identify inaccurate links that cannot
be detected by data linkage units that have access to personal identifiers only.
Perinatal researchers are encouraged to adopt the methods presented to ensure
quality and consistency among studies using linked administrative data.
PMID- 28693436
TI - Urinary schistosomiasis among vulnerable children in a rehabilitation home in
Ibadan, Oyo state, Nigeria.
AB - BACKGROUND: Schistosomiasis is a disease of public health importance with long
term complications mostly common among children, rural dwellers, poor and migrant
workers. Studies have not documented the burden among migrant workers and their
families. The study aimed to describe the burden of schistosomiasis and
demographic characteristics among children of migrant workers residing in a
rehabilitation home in Ibadan, Nigeria. METHODS: A cross-sectional study using
sixty six children, who were tested following complaints of haematuria by six of
them. An interviewer-administered questionnaire was used to collect information
on demographic and environmental characteristics of the children and urine
microscopy, was conducted. Data was analysed using descriptive statistics and
correlation. Statistical significance was set at 5%. RESULTS: Mean age of
respondents was 11.8 +/- 4.0 years and 57.6% were males. The prevalence of
schistosomiasis was 19.7% with preponderance among males (64.3%) and children
aged 12 years and above (71.4%); 85.7% of infected children were from Kwara
State; 78.6% waded in water body and 92.9% had red blood cells and pus cells on
urine microscopy. CONCLUSIONS: The burden of schistosomiasis is high among
children of migrant workers and they serve as reservoirs for transmission of the
disease. Government needs to work synergistically with NGOs, FBOs and other
partners to achieve schistosomiasis prevention and control among this particular
group.
PMID- 28693437
TI - Effects of computerized cognitive training on neuroimaging outcomes in older
adults: a systematic review.
AB - BACKGROUND: Worldwide, the population is aging and the number of individuals
diagnosed with dementia is rising rapidly. Currently, there are no effective
pharmaceutical cures. Hence, identifying lifestyle approaches that may prevent,
delay, or treat cognitive impairment and dementia in older adults is becoming
increasingly important. Computerized Cognitive Training (CCT) is a promising
strategy to combat cognitive decline. Yet, the underlying mechanisms of the
effect of CCT on cognition remain poorly understood. Hence, the primary objective
of this systematic review was to examine peer-reviewed literature ascertaining
the effect of CCT on both structural and functional neuroimaging measures among
older adults to gain insight into the underlying mechanisms by which CCT may
benefit cognitive function. METHODS: In accordance with PRISMA guidelines, we
used the following databases: MEDLINE, EMBASE, and CINAHL. Two independent
reviewers abstracted data using pre-defined terms. These included: main study
characteristics such as the type of training (i.e., single- versus multi-domain),
participant demographics (age >= 50 years; no psychiatric conditions), and the
inclusion of neuroimaging outcomes. The Physiotherapy Evidence Database (PEDro)
scale was used to assess quality of all studies included in this systematic
review. RESULTS: Nine studies were included in this systematic review, with four
studies including multiple MRI sequences. Results of this systematic review are
mixed: CCT was found to increase and decrease both brain structure and function
in older adults. In addition, depending on region of interest, both increases and
decreases in structure and function were associated with behavioural performance.
CONCLUSIONS: Of all studies included in this systematic review, results from the
highest quality studies, which were two randomized controlled trials,
demonstrated that multi-domain CCT could lead to increases in hippocampal
functional connectivity. Further high quality studies that include an active
control, a sample size calculation, and an appropriate training dosage, are
needed to confirm these findings and their relation to cognition.
PMID- 28693438
TI - Evaluation of recombinant porin (rOmp2a) protein as a potential antigen candidate
for serodiagnosis of Human Brucellosis.
AB - BACKGROUND: Brucellosis is an important zoonotic disease caused by different
Brucella species and human brucellosis is commonly prevalent in different states
of India. Among various Brucella species, B. melitensis is most pathogenic to
human and included as category B biothreat which can cause infection through
aerosol, cut, wounds in skin and contact with infected animals. The diagnosis of
human brucellosis is very important for proper treatment and management of
disease as there is no vaccine available for human use. The present study was
designed to clone, express and purify immunodominant recombinant omp2a (rOmp2a)
porin protein of B. melitensis and to evaluate this new antigen candidate for
specific serodiagnosis of human brucellosis by highly sensitive iELISA (indirect
enzyme linked immunosorbent assay). METHOD: Omp2a gene of B. melitensis 16 M
strain was cloned and expressed in pET-SUMO expression system. The recombinant
protein was purified under denaturing conditions using 8 M urea. The purified
recombinant protein was confirmed by western blotting by reacting with anti-HIS
antibody. The sero-reactivity of the recombinant protein was also checked by
reacting with antisera of experimentally infected mice with B. melitensis 16 M at
different time points. Serodiagnostic potential of recombinant porin antigen was
tested against 185 clinical serum samples collected from regions endemic to
brucellosis in southern part of India by iELISA. The samples were grouped into
five groups. Group 1 contained cultured confirmed positive serum samples of
brucellosis (n = 15), group 2 contained sera samples from positive cases of
brucellosis previously tested by conventional methods of RBPT (n = 28) and STAT
(n = 26), group 3 contained sera samples negative by RBPT(n = 36) and STAT (n =
32), group 4 contained sera samples of other febrile illness and PUO case (n =
35) and group 5 contained confirmed negative sera samples from healthy donors (n
= 23). RESULT: The rOmp2a was found to be immunoreactive by iELISA and western
blotting. The test showed a sensitivity of 93.75% and specificity of 95.83% when
tested against 185 serum samples. For determination of statistical significance
between experimental groups and control groups, Student's t test was performed on
the data. CONCLUSION: Omp2a emerges as a potential antigen candidate for
serodiagnosis of human brucellosis.
PMID- 28693439
TI - Combatting pain after orthopedic/trauma surgery- perioperative oral extended
release tapentadol vs. extended-release oxycodone/naloxone.
AB - BACKGROUND: High post-operative pain scores after "minor" orthopedic/trauma
surgery are in part attributed to inadequate prescription of opioid analgesics.
Novel concepts aiming to achieve sufficient analgesia while minimizing opioid
related side effects by avoiding fluctuating plasma levels are based on
perioperative oral administration of extended-release opioids beginning with the
first dose pre-operatively. This is the first study to evaluate analgesic
efficacy and side effect rates of extended-release tapentadol compared to
oxycodone/naloxone following orthopedic/trauma surgery. METHODS: This randomized,
observer-blinded, active-controlled prospective clinical trial had 2 co-primary
endpoints: (1) Analgesic efficacy: Mean pain level on a numeric rating scale
(NRS) from 0 to 10 during exercise over 5 days. (2) Safety: Side effect sum score
of the following events: Nausea, vomiting, constipation, sedation, vertigo,
somnolence. The study was powered to detect superiority of tapentadol for at
least one endpoint pending statistical proof of non-inferiority for both
endpoints in a first step. RESULTS: Two hundred sixty-six trauma patients were
randomized to receive either tapentadol (n = 133) or oxycodone/naloxone (n =
133). Analgesic efficacy: Mean (+/-SD) daily pain levels in the first five post
operative days were 2.8 +/- 1.3 in both groups. Mean maximum pain intensity
during exercise in the first 24 h after surgery was 3.8 +/- 1.9 (tapentadol) and
3.8 +/- 2.1 (oxycodone/naloxone). Statistically tapentadol was non-inferior but
not superior to oxycodone/naloxone. SAFETY: Vomiting on day 1 occurred in 11%,
constipation in 35% of the tapentadol patients and in 16% and 30% of the
oxycodone/naloxone patients (p = 0.60 and 0.33), respectively. The incidence of
sedation/ vertigo was <10%, that of somnolence <2% in both groups (p > 0.3,
respectively). The sum score of side effect events was 51% in the tapentadol vs.
49% in the oxycodone/naloxone group; risk difference 3% [95% CI, -8 to 14%]; p =
0.6). Non-inferiority of tapentadol could not be concluded as the pre-defined non
inferiority margin was exceeded. CONCLUSIONS: With both concepts, mean maximum
pain intensity during exercise within the first 24 h after orthopedic/trauma
surgery was reduced to a score of <4. This analgesic efficacy came at the cost of
mainly gastro-intestinal side effects. Thus, we now use a prophylaxis against
nausea and vomiting and pre-emptive laxatives as part of these concepts. TRIAL
REGISTRATION: https://eudract.ema.europa.eu (EudraCT- Nr. 2011-003238-15 );
October 24th, 2012.
PMID- 28693440
TI - Serum lactate level and mortality in metformin-associated lactic acidosis
requiring renal replacement therapy: a systematic review of case reports and case
series.
AB - BACKGROUND: The current practice concerning timing, mode, and dose of renal
replacement therapy (RRT) in patients with metformin-associated lactic acidosis
(MALA) with renal failure remains unknown. To investigate whether serum lactate
level and prescription pattern of RRT are associated with mortality in patients
with MALA requiring RRT. METHODS: We searched PubMed/Medline and EMBASE from
inception to Sep 2014 and applied predetermined exclusion criteria. Case-level
data including case's demographics and clinical information related to MALA were
abstracted. Multiple logistic regression modeling was used to examine the
predictors of mortality. RESULTS: A total of 253 unique cases were identified
with cumulative mortality of 17.2%. Eighty-seven percent of patients had acute
kidney injury. Serum lactate level was significantly higher in non-survivors
(median 22.5 mmol/L) than in survivors (17.0 mmol/L, p-value <0.01) and so did
the median blood metformin concentrations (58.5 vs. 43.9 mg/L, p-value = 0.05).
The survival advantage was not significantly different between the modalities of
RRT. The adjusted odds ratio of mortality for every one mmol/L increase in serum
lactate level was 1.09 (95% CI 1.02-1.17, p-value = 0.01). The dose-response
curve indicated a lactate threshold greater than 20 mmol/L was significantly
associated with mortality. CONCLUSIONS: Our study suggests that predialysis level
of serum lactate level is an important marker of mortality in MALA patients
requiring RRT with a linear dose-response relationship. To better evaluate the
optimal prescription of RRT in MALA, we recommend fostering an international
consortium to support prospective research and large-scale standardized case
collection.
PMID- 28693441
TI - CKD-EPI creatinine-cystatin C glomerular filtration rate estimation equation
seems more suitable for Chinese patients with chronic kidney disease than other
equations.
AB - BACKGROUND: The aim of this study was to identify the optimal equation that
accurately estimates the glomerular filtration rate (GFR) and the chronic kidney
disease (CKD) stage in the Chinese population. METHODS: A total of 1296 Chinese
patients aged 18-65 years old were enrolled in this study. The estimated GFRs
(eGFRs) calculated separately by three Diet in Renal Disease (MDRD) equations and
three Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations were
compared with the reference GFR (rGFR) measured by the 99Tcm-DTPA renal dynamic
imaging method. RESULTS: By Bland-Altman analysis, eGFRcys and eGFRscr_cys
performed similarly, showing the tightest limits of agreement among the six
equations. They also achieved the first and second highest 30% and 50%
accuracies. Using a combination of the serum creatinine and cystatin C levels
(eGFRscr_cys) could improve the bias (-0.3 for eGFRscr_cys) of the equation and
achieve the highest diagnostic accuracy for renal insufficiency (AUC60, 0.953; P
< 0.05, except for eGFR_MDRD). All equations predicted stage 3 CKD with moderate
accuracy (49.7-51.4%) and stage 5 CKD with good accuracy (90.2-96.4%). For stage
1 CKD, eGFRcys showed a higher percentage of misclassification than the other
equations. All equations seemed to perform poorly at predicting stage 2 and 4
CKD, as compared to the other CKD stages. eGFRscr_cys was the best-performing
equation in terms of accurate classification of the CKD stage based on the
overall performance (kappa value, 0.423). CONCLUSION: For a Chinese population,
the CKD-EPIscr_cys equation seems more suitable for estimating the GFR than the
other equations. Each equation had its own advantages in predicting different CKD
stages.
PMID- 28693442
TI - Evaluation of the relationship between MARCO and CD36 single-nucleotide
polymorphisms and susceptibility to pulmonary tuberculosis in a Chinese Han
population.
AB - BACKGROUND: Gene polymorphisms impact greatly on a person's susceptibility to
pulmonary tuberculosis (PTB). Macrophage receptor with collagenous structure
(MARCO) and CD36 are two scavenger receptors (SRs) that can recognize
Mycobacterium tuberculosis (Mtb) and play a key role in tuberculosis infection.
Gene polymorphisms of MARCO and CD36 may contribute to tuberculosis risk.
METHODS: To investigate whether genetic polymorphisms of MARCO and CD36 are
associated with susceptibility to PTB, genomic DNA samples from patients (n =
202) and healthy controls (n = 216) were collected and analyzed by polymerase
chain reaction with high-resolution melting analysis. RESULTS: We studied two
single nucleotide polymorphisms (SNPs) in MARCO (rs12998782 and rs17009726) and
three SNPs in CD36 (rs1194182, rs3211956 and rs10499859). Rs12998782 (P = 0.018)
might be associated with susceptibility to PTB. Rs1194182 (P < 0.01) and
rs10499859 (P < 0.001) might be associated with resistance to PTB. Rs17009726 and
rs3211956 were not associated with susceptibility/resistance to PTB. CONCLUSIONS:
These data showed that MARCO rs12998782 may increase PTB risk while two SNPs of
CD36, rs1194182 and rs10499859 may reduce the risk, indicating MARCO and CD36 as
important receptors in response to PTB.
PMID- 28693443
TI - Association of benzodiazepine and Z-drug use with the risk of hospitalisation for
fall-related injuries among older people: a nationwide nested case-control study
in Taiwan.
AB - BACKGROUND: Non-benzodiazepine hypnotics (Z-drugs) are advocated to be safer than
benzodiazepines (BZDs). This study comprehensively investigated the association
of BZD and Z-drug usage with the risk of hospitalisation for fall-related
injuries in older people. METHODS: This study used the Taiwan National Health
Insurance Database with a nested matched case-control design. We identified 2238
elderly patients who had been hospitalised for fall-related injuries between 2003
and 2012. They were individually matched (1:4) with a comparison group by age,
sex, and index year. Conditional logistic regression was used to determine
independent effects of drug characteristics (type of exposure, dosage, half-life,
and polypharmacy) on older people. RESULTS: Older people hospitalisation for fall
related injuries were significantly associated with current use of BZDs (adjusted
odds ratio [AOR] = 1.32, 95% confidential interval [CI] = 1.17-1.50) and Z-drugs
(AOR = 1.24, 95%CI = 1.05-1.48). At all dose levels of BZDs, high dose levels of
Z-drugs, long-acting BZD, and short-acting BZD use were all significantly
increased the risk of fall-related injuries requiring hospitalisation.
Polypharmacy, the use of two or more kinds of BZDs, one kind of BZD plus Z-drugs
and two or more kinds of BZDs plus Z-drugs, also significantly increased the risk
(AOR = 1.61, 95% CI = 1.38-1.89; AOR = 1.65, 95% CI = 1.08-2.50, and AOR = 1.58,
95% CI = 1.21-2.07). CONCLUSIONS: Different dose levels and half-lives of BZDs, a
high dose of Z-drugs, and polypharmacy with BZDs and Z-drugs were associated with
an increased risk of fall-related injury requiring hospitalisation in older
people. Physicians should balance the risks and benefits when prescribing these
drug regimens to older people considering the risk of falls.
PMID- 28693444
TI - The value of ultrasound-guided biopsy of fluorodeoxy-glucose positron emission
tomography (FDG-PET)-positive supraclavicular lymph nodes in patients with
suspected lung cancer.
AB - BACKGROUND: Accurate lymph node staging is essential for adequate prognostication
and therapy planning in patients with non-small cell lung cancer (NSCLC). FDG
PET/CT is a sensitive tool for the detection of metastases, including non
palpable supraclavicular lymph node (SCLN) metastases. Histological proof of
metastatic spread and mutation analysis is crucial for optimal staging and
therapy. The aim of this study was to investigate the value of ultrasound-guided
fine needle aspiration cytology (FNAC) and core biopsy (CB) of FDG active, non
palpable SCLN's in patients with suspicion for lung cancer. METHODS: Twelve
consecutive patients with suspected lung cancer and FDG-positive SCLN underwent
FNAC (n = 11) and/or CB (n = 10) and were included and evaluated retrospectively
in this study. Cytologic and/or histologic evaluation was performed to confirm
initially suspected diagnosis (lung cancer), to confirm N3 stage, and to screen
for driver mutations in lung adenocarcinoma. RESULTS: FNAC alone showed
diagnostic success in 11/11 cases (100%), CB alone in 9/10 patients (90%), and
the combination of both procedures was successful in 12/12 cases (100%). Lymph
node metastases from NSCLC (7 adenocarcinoma, 2 squamous cell carcinoma) could be
confirmed in 9 patients. Other diagnoses were small cell lung cancer (SCLC),
breast cancer and sarcoidosis. There was enough material for immunhistochemistry
in all patients. For molecular testing, material from this lymph node biopsies
and lung biopsy was used. In two patients with adenocarcinoma of the lung driver
mutations were detected (EGFR Exon 19 deletion and ALK rearrangement) out of the
lymph node metastasis. CONCLUSIONS: US-guided combined FNAC and CB of FDG
positive supraclavicular lymph nodes in patients with suspected lung cancer is a
safe and effective procedure to confirm N3-stage and to obtain representative
material for molecular testing.
PMID- 28693445
TI - Older persons' existential loneliness, as interpreted by their significant others
- an interview study.
AB - BACKGROUND: In order to better understand people in demanding medical situations,
an awareness of existential concerns is important. Studies performed over the
last twenty years conclude that when dying and death come closer, as in the case
with older people who are stricken by infirmity and diseases, existential
concerns will come to the fore. However, studies concerning experiences of
existential loneliness (EL) are sparse and, in addition, there is no clear
definition of EL. EL is described as a complex phenomenon and referred to as a
condition of life, an experience, and a process of inner growth. Listening to
someone who knows the older person well, as significant others often do, may be
one way of learning more about EL. METHODS: This study is part of a larger
research project on EL, the LONE study, where EL is explored through interviews
with frail older people, their significant others and health care professionals.
The aim of this study was to explore frail older (>75) persons' EL, as
interpreted by their significant others. The study is qualitative and based on
eighteen narrative interviews with nineteen significant others of older persons.
The data was analysed using Hsieh and Shannon's conventional content analysis.
RESULTS: According to the interpretation of significant others, the older persons
experience EL (1) when they are increasingly limited in body and space, (2) when
they are in a process of disconnecting, and (3) when they are disconnected from
the outside world. CONCLUSION: The result can be understood as if the frail older
person is in a process of letting go of life. This process involves the body, in
that the older person is increasingly limited in his/her physical abilities. The
older person's long-term relationships are gradually lost, and finally the
process entails the older person's increasingly withdrawing into him- or herself
and turning off the outside world. The result of this study is consistent with
previous research that has shown that EL is a complex phenomenon, but the
implications of this research include a deepened understanding of EL. In
addition, the study highlights the interpretations of significant others.
PMID- 28693446
TI - Response to immunosuppressive therapy in PLA2R- associated and non-PLA2R-
associated idiopathic membranous nephropathy: a retrospective, multicenter cohort
study.
AB - BACKGROUND: According to renal M type phospholipase A2 receptor (PLA2R)
immunohistochemistry, idiopathic membranous nephropathy (IMN) could be
categorized into PLA2R-associated and non-PLA2R-associated IMN. We conducted a
retrospective, multicenter cohort study with 91 patients to compare the effect of
immunosuppressive therapy between PLA2R-associated and non-PLA2R-associated IMN
patients. METHODS: A total of 91 biopsy-proven IMN patients from Huashan hospital
and People's Hospital of Wuxi in past 5 years were collected into this study. IMN
with positive PLA2R immunohistochemistry in kidney biopsies were designated as
PLA2R-associated IMN. Seventy-eight of the 91 IMN patients was PLA2R-associated
IMN and 13 were non-PLA2R-associated IMN. Forty-five patients were treated with
prednisone plus cyclophosphamide (CTX), and 46 with prednisone plus calcineurin
inhibitors (CNIs). The follow-up duration was 15 months. RESULTS: The total
remission rate (76.9% versus 44.9%, p = 0.032) and complete remission rate (30.8%
versus 2.6%, p = 0.003) were both significantly higher in the non-PLA2R
associated group than in the PLA2R-associated group at the 3rd month visit point,
and at the 6th month time point, the complete remission rate was still
significantly higher in the non-PLA2R-associated group (46.2% versus 11.5%,p =
0.007). But similar remission rates were found after the 9th month. Relapses were
observed in 8 patients in PLA2R-associated group and none in non-PLA2R-associated
group, although there was no significant difference between these two groups.
CONCLUSION: Compared with the PLA2R-associated IMN, the non-PLA2R-associated IMN
responded quicker to the immunosuppressive therapy.
PMID- 28693447
TI - A cost effectiveness analysis of midwife psycho-education for fearful pregnant
women - a health system perspective for the antenatal period.
AB - BACKGROUND: Psycho-education can reduce childbirth fear and caesarean section
numbers. This study determines the cost-effectiveness of a midwife-led psycho
education intervention for women fearful of birth. METHOD: One thousand four
hundred ten pregnant women in south-east Queensland, Australia were screened for
childbirth fear (W-DEQ A >= 66). Women with high scores (n = 339) were randomised
to the BELIEF Study (Birth Emotions and Looking to Improve Expectant Fear) to
receive psycho-education (n = 170) at 24 and 34 weeks of pregnancy or to the
control group (n = 169). Women in both groups were surveyed 6 weeks postpartum
with total cost for health service use during pregnancy calculated. Logistic
regression models assessed the odds ratio of having vaginal birth or caesarean
section in the study groups. RESULT: Of 339 women randomised, 184 (54%) women
returned data at 6 weeks postpartum (Intervention Group n = 91; Control Group n =
93). Women receiving psycho-education had a higher likelihood of vaginal birth
compared to controls (n = 60, 66% vs. n = 54, 58%; OR 2.34). Mean 'treatment'
cost for women receiving psycho-education was AUS$72. Mean cost for health
services excluding the cost of psycho-education, was less in the intervention
group (AUS$1193 vs. AUS$1236), but not significant (p = 0.78). For every five
women who received midwife counselling, one caesarean section was averted. The
incremental healthcare cost to prevent one caesarean section using this
intervention was AUS$145. CONCLUSION: Costs of delivering midwife psycho
education to women with childbirth fear during pregnancy are offset by improved
vaginal birth rates and reduction in caesarean section numbers. TRIAL
REGISTRATION: Australian New Zealand Controlled Trials Registry
ACTRN12612000526875 , 17th May 2012 (retrospectively registered one week after
enrolment of first participant).
PMID- 28693448
TI - High cancer mortality for US-born Latinos: evidence from California and Texas.
AB - BACKGROUND: Latinos born in the US, 36 million, comprise 65% of all US Latinos.
Yet their cancer experience is nearly always analyzed together with their foreign
born counterparts, 19 million, who constitute a steady influx of truly lower-risk
populations from abroad. To highlight specific cancer vulnerabilities for US-born
Latinos, we compare their cancer mortality to the majority non-Latino white (NLW)
population, foreign-born Latinos, and non-Latino blacks. METHODS: We analyzed
465,751 cancer deaths from 2008 to 2012 occurring among residents of California
and Texas, the two most populous states, accounting for 47% of US Latinos. This
cross-sectional analysis, based on granular data obtained from death certificates
on cause of death, age, race, ethnicity and birthplace, makes use of normal
standardization techniques and negative binomial regression models. RESULTS:
While Latinos overall have lower all-cancers-combined mortality rates than NLWs,
these numbers were largely driven by low rates among the foreign born while
mortality rates for US-born Latinos approach those of NLWs. Among Texas males,
rates were 210 per 100,000 for NLWs and 166 for Latinos combined, but 201 per
100,000 for US-born Latinos and 125 for foreign-born Latinos. Compared to NLWs,
US-born Latino males in California had mortality rate ratios of 2.83 (95% CI:
2.52-3.18) for liver cancer, 1.44 (95% CI: 1.30-1.61) for kidney cancer, and 1.25
(95% CI: 1.17-1.34) for colorectal cancer (CRC). Texas results showed a similar
site-specific pattern. CONCLUSIONS: Specific cancer patterns for US-born Latinos,
who have relatively high cancer mortality, similar overall to NLWs, are masked by
aggregation of all Latinos, US-born and foreign-born. While NLWs had high
mortality for lung cancer, US-born Latinos had high mortality for liver, kidney
and male colorectal cancers. HCV testing and reinforcement of the need for CRC
screening should be a priority in this specific and understudied population. The
unprecedented proximity of overall rates between NLWs and US-born Latino
populations runs counter to the prevailing narrative of Latinos having
significantly lower cancer risk and mortality. Birthplace data are critical in
detecting meaningful differences among Latinos; these findings merit not only
clinical but also public health attention.
PMID- 28693449
TI - Multiparametric magnetic resonance imaging in mucosal primary head and neck
cancer: a prospective imaging biomarker study.
AB - BACKGROUND: Radical radiotherapy, with or without concomitant chemotherapy forms
the mainstay of organ preservation approaches in mucosal primary head and neck
cancer. Despite technical advances in cancer imaging and radiotherapy
administration, a significant proportion of patients fail to achieve a complete
response to treatment. For those patients who do achieve a complete response,
acute and late toxicities remain a cause of morbidity. A critical need therefore
exists for imaging biomarkers which are capable of informing patient selection
for both treatment intensification and de-escalation strategies. METHODS/DESIGN:
A prospective imaging study has been initiated, aiming to recruit patients
undergoing radical radiotherapy (RT) or chemoradiotherapy (CRT) for mucosal
primary head and neck cancer (MPHNC). Eligible patients are imaged using FDG
PET/CT before treatment, at the end of week 3 of treatment and 12 weeks after
treatment completion according to local imaging policy. Functional MRI using
diffusion weighted (DWI), blood oxygen level-dependent (BOLD) and dynamic
contrast enhanced (DCE) sequences is carried out prior to, during and following
treatment. Information regarding treatment outcomes will be collected, as well as
physician-scored and patient-reported toxicity. DISCUSSION: The primary objective
is to determine the correlation of functional MRI sequences with tumour response
as determined by FDG-PET/CT and clinical findings at 12 weeks post-treatment and
with local control at 12 months post-treatment. Secondary objectives include
prospective correlation of functional MRI and PET imaging with disease-free
survival and overall survival, defining the optimal time points for functional
MRI assessment of treatment response, and determining the sensitivity and
specificity of functional MRI sequences for assessment of potential residual
disease following treatment. If the study is able to successfully characterise
tumours based on their functional MRI scan characteristics, this would pave the
way for further studies refining treatment approaches based on prognostic and
predictive imaging data. TRIAL REGISTRATION: Australian New Zealand Clinical
Trials Registry (ANZCTR): ACTRN12616000534482 (26 April 2016).
PMID- 28693450
TI - Transition to parenthood in the neonatal care unit: a qualitative study and
conceptual model designed to illuminate parent and professional views of the
impact of webcam technology.
AB - BACKGROUND: Complications during pregnancy, childbirth and/or the postnatal
period may result in the admission of a baby to a neonatal unit (NNU). While the
survival and long-term prospects of high-risk infants are enhanced by admission,
the enforced separation of the parent and child may have psychological
consequences for both. There is a need to develop and evaluate interventions to
help parents 'feel closer' to their infants in circumstances where they are
physically separated from them. In this paper we present findings from an in
depth, theoretically-driven, evaluation of a technological innovation designed to
address this need. The study sought to explore parent and professional views of
the impact of the technology, which transmits real-time images of the baby via a
webcam from the NNU to the mother's bedside in the post-natal care environment.
METHODS: A qualitative approach was adopted, guided by a critical realist
perspective. Participants were recruited purposively from a NNU located in East
central Scotland. Thirty-three parents and 18 professionals were recruited. Data
were collected during individual, paired and small group interviews and were
analysed thematically. Following the initial analysis process, abductive
inference was used to consider contextual factors and mechanisms of action
appearing to account for reported outcomes. RESULTS: Views on the technology were
overwhelmingly positive. It was perceived as a much needed and important
advancement in care delivery. Benefits centred on: enhanced feelings of closeness
and responsiveness; emotional wellbeing; physical recovery; and the involvement
of family/friends. These benefits appeared to function as important mechanisms in
supporting the early bonding process and wider transition to parenthood. However,
for a small number of the parents, use of the technology had not enhanced their
experience and it is important, as with any intervention, that professionals
monitor the parents' response and act accordingly. CONCLUSIONS: With a current
global increase in premature births, the technology appears to offer an important
solution to periods of enforced parent-infant separation in the early post-natal
period. The current study is one of a few world-wide to have sought to evaluate
this form of technology in the neonatal care environment.
PMID- 28693451
TI - A cross-sectional analysis of green space prevalence and mental wellbeing in
England.
AB - BACKGROUND: With urbanisation increasing, it is important to understand how to
design changing environments to promote mental wellbeing. Evidence suggests that
local-area proportions of green space may be associated with happiness and life
satisfaction; however, the available evidence on such associations with more
broadly defined mental wellbeing in still very scarce. This study aimed to
establish whether the amount of neighbourhood green space was associated with
mental wellbeing. METHODS: Data were drawn from Understanding Society, a national
survey of 30,900 individuals across 11,096 Census Lower-Layer Super Output Areas
(LSOAs) in England, over the period 2009-2010. Measures included the multi
dimensional Warwick-Edinburgh Mental Well-Being Scale (SWEMWBS) and LSOA
proportion of green space, which was derived from the General Land Use Database
(GLUD), and were analysed using linear regression, while controlling for
individual, household and area-level factors. RESULTS: Those living in areas with
greater proportions of green space had significantly higher mental wellbeing
scores in unadjusted analyses (an expected increase of 0.17 points (95% CI 0.11,
0.23) in the SWEMWBS score for a standard deviation increase of green space).
However, after adjustment for confounding by respondent sociodemographic
characteristics and urban/rural location, the association was attenuated to the
null (regression coefficient B = - 0.01, 95% CI -0.08, 0.05, p = 0.712).
CONCLUSIONS: While the green space in an individual's local area has been shown
through other research to be related to aspects of mental health such as
happiness and life satisfaction, the association with multidimensional mental
wellbeing is much less clear from our results. While we did not find a
statistically significant association between the amount of green space in
residents' local areas and mental wellbeing, further research is needed to
understand whether other features of green space, such as accessibility,
aesthetics or use, are important for mental wellbeing.
PMID- 28693452
TI - Ascorbic acid concentrations in aqueous humor after systemic vitamin C
supplementation in patients with cataract: pilot study.
AB - BACKGROUND: To measure ascorbic acid concentration in aqueous humor of patients
with cataract after oral or intravenous vitamin C supplementation. METHODS: Forty
two eyes of 42 patients with senile cataract who underwent uncomplicated cataract
surgery were enrolled. Patients (n = 14 each) were administered oral vitamin C (2
g), intravenous vitamin C (20 g) or no treatment (control group) on the day
before surgery. Samples of aqueous humor (0.1 cm3) were obtained by anterior
chamber aspiration at the beginning of surgery and stored at -80 degrees C.
Ascorbic acid concentration in aqueous humor was measured by high-pressure liquid
chromatography. RESULTS: The mean age at surgery was 62.5 years, with no
difference among the three groups. The mean +/- standard deviation concentrations
of ascorbic acid in aqueous humor in the control and oral and intravenous vitamin
C groups were 1347 +/- 331 MUmol/L, 1859 +/- 408 MUmol/L and 2387 +/- 445
MUmol/L, respectively. Ascorbic acid concentration was significantly lower in the
control than in the oral (P < 0.01) and intravenous (P < 0.001) vitamin C groups
and was significantly higher in the intravenous than in the oral vitamin C group
(P < 0.05). CONCLUSIONS: Ascorbic acid concentration in aqueous humor is
increased by systemic vitamin C supplementation, with intravenous administration
being more effective than oral administration.
PMID- 28693453
TI - An account of the Ebola virus disease outbreak in Nigeria: implications and
lessons learnt.
AB - BACKGROUND: The 2014 Ebola virus disease (EVD) outbreak remains unprecedented
both in the number of cases, deaths and geographic scope. The first case of EVD
was confirmed in Lagos Nigeria on 23 July 2014 and spread to involve 19
laboratory-confirmed EVD cases. The EVD cases were not limited to Lagos State as
Rivers State recorded 2 confirmed cases of EVD with 1 out of the 2 dying. Swift
implementation of public health measures were sufficient to forestall a country
wide spread of this dreaded disease. This exploratory formative research
describes the events of the Nigeria Ebola crisis in 2014. METHODS: This research
was implemented through key informant in-depth interviews involving 15
stakeholders in the EVD outbreak in Nigeria by a team of two or three
interviewers. Most of the interviews were conducted face-to-face at the various
offices of the respondents and others were via the telephone. The interviews
which lasted an hour on average were conducted in English, digitally recorded and
notes were also taken. RESULTS: This study elucidated the public health response
to the Ebola outbreak led by Lagos State Government in conjunction with the
Federal Ministry of Health. The principal strategy was an incident management
approach which saw them identify and successfully follow up 894 contacts. The
infected EVD cases were quarantined and treated. The Nigerian private sector and
international organizations made significant contributions to the control
efforts. Public health enlightenment programmes using multimodal communication
strategies were rapidly deployed. Water and sanitary facilities were provided in
many public schools in Lagos. CONCLUSIONS: The 2014 Ebola outbreak in Nigeria was
effectively controlled using the incident management approach with massive
support provided by the private sector and international community. Eight of the
confirmed cases of EVD in Nigeria eventually died (case fatality rate of 42.1%)
and twelve were nursed back to good health. On October 20 2014 Nigeria was
declared fee of EVD by the World Health Organization. The Nigerian EVD experience
provides valuable insights to guide reforms of African health systems in
preparation for future infectious diseases outbreaks.
PMID- 28693454
TI - Design and methods for a cluster-controlled trial conducted at sixty-eight
daycare facilities evaluating the impact of "JolinchenKids - Fit and Healthy in
Daycare", a program for health promotion in 3- to 6-year-old children.
AB - BACKGROUND: The prevention of overweight and obesity during infancy is a highly
relevant public health topic given the significant impact of childhood obesity on
acute and chronic diseases, general health, and well-being in later stages of
life. Apart from the family setting, daycare facilities (DFs) represent a key
setting for health promotion among children under the age of six years.
"JolinchenKids - Fit and Healthy in Daycare" is a multi-component program
promoting physical activity (PA), healthy eating, and mental well-being in 3- to
6-year-old preschoolers at DFs, originally designed by the German health
insurance AOK. To evaluate program effectiveness, a cluster-controlled trial
involving 68 DFs is currently conducted. The objective of this article is to
describe the background, study design, and aims of this trial. METHODS/DESIGN:
Sixty-eight DFs across Germany will be recruited to take part in the study, half
of them serving as intervention DFs and half of them as delayed intervention
control DFs (which receive the program upon completion of the study). At each DF,
height, weight, and body composition, as well as motor skills, will be assessed
in twenty 3- to 6-year-old children. Children's eating and PA habits, and mental
well-being will be assessed via parental questionnaires. A subsample of children
(i.e., at 24 DFs which are randomly selected within a geographic region) will be
asked to wear accelerometers at their wrists to objectively measure PA over the
course of seven days. To compare changes in body composition, motor skills,
eating and PA habits, and mental well-being of children at intervention DFs with
those observed among children at delayed intervention control DFs over one year,
all measurements will take place at baseline and twelve months after the launch
of the program at all DFs. DISCUSSION: This study investigates the influence of a
health promotion program in the daycare setting on various outcomes, including
body composition and objectively measured PA, in a nationwide sample of 3- to 6
year-old preschoolers. This study will provide evidence regarding the
effectiveness of a multi-component program for health promotion in this setting
and may provide insights into new strategies for preventing obesity in early
life. TRIAL REGISTRATION: German Clinical Trials Register DRKS00011065 (Date of
registration 16-09-2016).
PMID- 28693455
TI - Fainting Fanconi syndrome clarified by proxy: a case report.
AB - BACKGROUND: Rare diseases may elude diagnosis due to unfamiliarity of the
treating physicians with the specific disorder. Yet, advances in genetics have
tremendously enhanced our ability to establish specific and sometimes surprising
diagnoses. CASE PRESENTATION: We report a case of renal Fanconi syndrome
associated with intermittent hypoglycemic episodes, the specific cause for which
remained elusive for over 30 years, despite numerous investigations, including
three kidney and one liver biopsy. The most recent kidney biopsy showed
dysmorphic mitochondria, suggesting a mitochondrial disorder. When her son
presented with hypoglycemia in the neonatal period, he underwent routine genetic
testing for hyperinsulinemic hypoglycemia, which revealed a specific mutation in
HNF4A. Subsequent testing of the mother confirmed the diagnosis also in her.
CONCLUSION: Modern sequencing technologies that test multiple genes
simultaneously enable specific diagnoses, even if the underlying disorder was not
clinically suspected. The finding of mitochondrial dysmorphology provides a
potential clue for the mechanism, by which the identified mutation causes renal
Fanconi syndrome.
PMID- 28693456
TI - Impact of large-scale distribution and subsequent use of free nicotine patches on
primary care physician interaction.
AB - BACKGROUND: Large-scale distribution efforts of free nicotine replacement therapy
(NRT) have been documented to be cost-effective interventions for increasing
smoking quit rates. However, despite nearly a dozen studies evaluating their
effectiveness, none have examined whether free NRT provision promotes further
primary care help-seeking and the impact that it may have on cessation efforts.
METHODS: In the context of a randomized controlled trial, a secondary analysis
was conducted on 1000 adult regular smokers randomized to be mailed a 5-week
supply of nicotine patches or to a no intervention control group. Recipients and
users of free nicotine patches at an 8 week follow-up were successfully case
matched to controls based on age, gender, baseline level of nicotine dependence
and intent to quit (n = 201 per group). Differences in physician interaction
between the two groups were evaluated at both 8 week and 6 month follow-ups. The
impact of physician interaction on self-reported smoking abstinence at each
follow-up was also examined. RESULTS: Although no differences in physician
interaction were noted between groups at the 8 week follow-up, at the 6 month
follow-up, nicotine patch users reported greater frequency of discussing smoking
with their physician (43.9%), as compared to the control group (30.3%) (p =
0.011). Across both groups, over 90% of those that discussed smoking with a
physician were encouraged to quit and approximately 70% were provided with
additional support. Separate ANOVAs revealed no significant impact of physician
interaction on cessation (p > 0.05), regardless of group or follow-up period,
however, at the 6 month follow-up, nicotine patch users who discussed cessation
with a physician had made serious quit attempts at significantly greater rates
(72.6%), compared to controls (49.1%) (p = 0.007). CONCLUSIONS: Irrespective of
group, the majority of smokers in the present study did not discuss cessation
with their physician. Recipients and users of nicotine patches however, were more
likely to discuss smoking with their physician, suggesting that the provision of
free NRT particularly to those who are likely to use it may facilitate
opportunities for benefits beyond the direct pharmacological effects of the
medication. TRIAL REGISTRATION: clinicaltrials.gov , NCT01429129 . Registered: 2
September 2011.
PMID- 28693457
TI - Calculation of iris-claw IOL power for correction of late in-the-bag IOL complex
dislocation.
AB - BACKGROUND: To assess the constants and formula for aphakia correction with iris
claw IOLs to achieve the best refractive status in cases of late in-the-bag IOL
complex dislocation. METHODS: A literature search was performed. The following
data were obtained: Iris-claw IOL model, Iridal or retroiridal enclavation, A
constant, ultrasound or optical biometry, formula employed and refractive
outcomes. Acceptable emmetropia was considered if the resulting spherical
equivalent (SE) was within +/-1.00 D. RESULTS: The majority of the studies used
SRK/T formula (66.6%). The 88.9% of the reports obtained a SE within +/-1.00 D.
Using A-115 for ultrasound biometry and A-115.7 for optical biometry and SRK/T
formula, the emmetropia (+/-1.00 D) of SE, was able to get near 100% of reported
cases over the pupil implantation. However, the emmetropia decreased to 80% when
the enclavation is retropupilar using the same formula. The A-constant can vary
from 116.7 to 117.5 for retropupilar enclavation. CONCLUSIONS: Using A-115 for
ultrasound biometry and A-115.7 for optical biometry and SRK/T formula, +/-1.00 D
of SE, is able to get near 100% of cases. Nevertheless, +/-1.00 D of SE decreased
to 80% of the cases when the enclavation is retropupilar.
PMID- 28693458
TI - A population-based national estimate of the prevalence and risk factors
associated with hypertension in Rwanda: implications for prevention and control.
AB - BACKGROUND: Hypertension is a leading cause of cardiovascular diseases and a
growing public health problem in many developed and developing countries.
However, population-based data to inform policy development are scarce in Rwanda.
This nationally representative study aimed to determine population-based
estimates of the prevalence and risk factors associated with hypertension in
Rwanda. METHODS: We conducted secondary epidemiological analysis of data
collected from a cross-sectional population-based study to assess the risk
factors for NCDs using the WHO STEPwise approach to Surveillance of non
communicable diseases (STEPS). Adjusted odds ratios at 95% confidence interval
were used to establish association between hypertension, socio-demographic
characteristics and health risk behaviors. RESULTS: Of the 7116 study
participants, 62.8% were females and 38.2% were males. The mean age of study
participants was 35.3 years (SD 12.5). The overall prevalence of hypertension was
15.3% (16.4% for males and 14.4% for females). Twenty two percent of hypertensive
participants were previously diagnosed. A logistic regression model revealed that
age (AOR: 8.02, 95% CI: 5.63-11.42, p < 0.001), living in semi-urban area (AOR:
1.30, 95% CI: 1.01-1.67, p = 0.040) alcohol consumption (AOR: 1.24, 95% CI: 1.05
1.44, p = 0.009) and, raised BMI (AOR: 3.93, 95% CI: 2.54-6.08, p < 0.001) were
significantly associated with hypertension. The risk of having hypertension was 2
times higher among obese respondents (AOR: 3.93, 95% CI: 2.54-6.08, p-value <
0.001) compared to those with normal BMI (AOR: 1.74, 95% CI: 1.30-2.32, p-value <
0.001). Females (AOR: 0.75, 95% CI: 0.63-0.88, p < 0.001) and students (AOR:
0.45, 95% CI: 0.25-0.80, p = 0.007) were less likely to be hypertensive.
CONCLUSION: The findings of this study indicate that the prevalence of
hypertension is high in Rwanda, suggesting the need for prevention and control
interventions aimed at decreasing the incidence taking into consideration the
risk factors documented in this and other similar studies.
PMID- 28693459
TI - Screening for glucose-6-phosphate dehydrogenase deficiency in neonates: a
comparison between cord and peripheral blood samples.
AB - BACKGROUND: The use of cord blood in the neonatal screening for glucose-6
phosphate dehydrogenase (G6PD) deficiency is being done with increasing frequency
but has yet to be adequately evaluated against the use of peripheral blood sample
which is usually employed for confirmation. We sought to determine the incidence
and gender distribution of G6PD deficiency, and compare the results of cord
against peripheral blood in identifying G6PD DEFICIENCY neonates using
quantitative enzyme activity assay. METHODS: We carried out a retrospective and
cross-sectional study employing review of primary hospital data of neonates born
in a tertiary care center from January to December 2008. RESULTS: Among the 8139
neonates with cord blood G6PD assays, an overall incidence of 2% for G6PD
deficiency was computed. 79% of these were males and 21% were females with
significantly more deficient males (p < .001). Gender-specific incidence was
3.06% for males and 0.85% for females. A subgroup analysis comparing cord and
peripheral blood samples (n = 1253) showed a significantly higher mean G6PD value
for peripheral than cord blood (15.12 +/- 4.52 U/g and 14.52 +/- 4.43 U/g,
respectively, p = 0.0008). However, the proportion of G6PD deficient neonates did
not significantly differ in the two groups (p = 0.79). Sensitivity of cord blood
in screening for G6PD deficiency, using peripheral G6PD assay as a gold standard
was 98.6% with a NPV of 99.5%. CONCLUSION: There was no difference between cord
and peripheral blood samples in discriminating between G6PD deficient and non
deficient neonates. A significantly higher mean peripheral G6PD assay reinforces
the use of cord blood for neonatal screening since it has substantially low false
negative results.
PMID- 28693460
TI - LinkImputeR: user-guided genotype calling and imputation for non-model organisms.
AB - BACKGROUND: Genomic studies such as genome-wide association and genomic selection
require genome-wide genotype data. All existing technologies used to create these
data result in missing genotypes, which are often then inferred using genotype
imputation software. However, existing imputation methods most often make use
only of genotypes that are successfully inferred after having passed a certain
read depth threshold. Because of this, any read information for genotypes that
did not pass the threshold, and were thus set to missing, is ignored. Most
genomic studies also choose read depth thresholds and quality filters without
investigating their effects on the size and quality of the resulting genotype
data. Moreover, almost all genotype imputation methods require ordered markers
and are therefore of limited utility in non-model organisms. RESULTS: Here we
introduce LinkImputeR, a software program that exploits the read count
information that is normally ignored, and makes use of all available DNA sequence
information for the purposes of genotype calling and imputation. It is
specifically designed for non-model organisms since it requires neither ordered
markers nor a reference panel of genotypes. Using next-generation DNA sequence
(NGS) data from apple, cannabis and grape, we quantify the effect of varying read
count and missingness thresholds on the quantity and quality of genotypes
generated from LinkImputeR. We demonstrate that LinkImputeR can increase the
number of genotype calls by more than an order of magnitude, can improve
genotyping accuracy by several percent and can thus improve the power of
downstream analyses. Moreover, we show that the effects of quality and read depth
filters can differ substantially between data sets and should therefore be
investigated on a per-study basis. CONCLUSIONS: By exploiting DNA sequence data
that is normally ignored during genotype calling and imputation, LinkImputeR can
significantly improve both the quantity and quality of genotype data generated
from NGS technologies. It enables the user to quickly and easily examine the
effects of varying thresholds and filters on the number and quality of the
resulting genotype calls. In this manner, users can decide on thresholds that are
most suitable for their purposes. We show that LinkImputeR can significantly
augment the value and utility of NGS data sets, especially in non-model organisms
with poor genomic resources.
PMID- 28693461
TI - Social network correlates of HIV risk-related behaviors among male migrants in
China.
AB - BACKGROUND: Significant domestic and global research has focused on HIV risk
among China's large internal migrant population. Much of this work takes an
individual behavior approach while ignoring the critical role social networks
play in shaping HIV risk. METHODS: Based on past studies among migrant men in
China of yingchou activities (activities that build and reinforce social networks
such as eating, drinking alcohol and patronizing commercial sex), we constructed
ego-centric networks for a sample of 385 male migrants recruited from multiple
worksites in Beijing. We used a nested-model approach to examine the contribution
of social network characteristics to HIV risk at both the variable and model
levels. RESULTS: As compared to an individual-level model, addition of social
network variables significantly improved the fit of the models. Commercial sex
norms and condom use norms of core yingchou networks were significantly
associated with egos' commercial sex and condom use respectively. The size of
yingchou network was associated with egos' commercial sex. The network models
became more sensitive after network norm measures took into account the intimacy
of network ties and allowed for egos' uncertainty when reporting their alters'
sexual behaviors. CONCLUSION: Results suggest the importance of social network
factors and core network members in HIV transmission and risk-reduction
interventions for male migrants. Future studies could explore other important
social networks among male migrants, consider the intimacy of network ties and
egos' uncertainty about alters' situations in constructing network norms, and
refine the measurement of network size and density.
PMID- 28693462
TI - The Antibiotic Guardian campaign: a qualitative evaluation of an online pledge
based system focused on making better use of antibiotics.
AB - BACKGROUND: The Antibiotic Guardian Campaign was developed to increase commitment
to reducing Antimicrobial Resistance (AMR), change behaviour and increase
knowledge through an online pledge system for healthcare professionals and
members of the public to become Antibiotic Guardians (AG). This qualitative
evaluation aimed to understand AG experiences of the campaign and perceived
impact on behaviour. METHODS: Ninety-four AGs (48 via a survey and 46 who had
agreed to future contact) were invited to participate in a telephone semi
structured interview. The sample was based on self-identification as a healthcare
professional or a member of the public, pledge group (e.g. adults, primary care
prescribers etc.), pledge and gender. Interviews explored how participants became
aware of the campaign, reasons for joining, pledge choices, responses to joining
and views about the campaign's implementation. Interviews were analysed using the
Framework Method. RESULTS: Twenty-two AGs (10 healthcare professionals and 12
members of the public) were interviewed. AGs became aware of the campaign through
professional networks and social media, and were motivated to join by personal
and professional concern for AMR. Choice of pledge group and pledge were
attributed to relevance and potential impact on AMR and the behaviour of others
through pledge enactment and promotion of the campaign. Most AGs could not recall
their pledge unprompted. Most felt they fulfilled their pledge, although this
reflected either behaviour change or the pledge reinforcing pre-existing
behaviour. The campaign triggered AGs to reflect on AMR related behaviour and
reinforced pre-existing beliefs. Several AGs promoted the campaign to others.
Responding collectively as part of the campaign was thought to have a greater
impact than individual action. However, limited campaign visibility was observed
and the campaign was perceived to have restricted ability to reach those unaware
of AMR. CONCLUSIONS: AGs were motivated to reduce AMR and most felt they
fulfilled their pledges although for many this appeared to be through
reinforcement of existing behaviours. We recommend that the campaign engages
those without pre-existing knowledge of AMR by increasing its visibility,
capitalising on the diffusion of its message and including more awareness-raising
content for those with limited AMR knowledge.
PMID- 28693463
TI - Descriptive analysis of cochrane child-relevant systematic reviews: an update and
comparison between 2009 and 2013.
AB - BACKGROUND: Systematic reviews support health systems and clinical decision
making by identifying and summarizing all existing studies on a particular topic.
In 2009, a comprehensive description of child-relevant systematic reviews
published in the Cochrane Database of Systematic Reviews was compiled. This study
aims to provide an update, and to describe these systematic reviews according to
their content and methodological approaches. METHODS: All child-relevant
systematic reviews published by the Cochrane Collaboration in the Cochrane
Database of Systematic Reviews (CDSR) as of March, 2013 were identified and
described in relation to their content and methodological approaches. This step
equated to an update of the Child Health Field Review Register (CHFRR). The
content of the updated CHFRR was compared to the published 2009 CHFRR description
regarding clinical and methodological characteristics, using bivariate analyses.
As the Cochrane Collaboration has recognized that disease burden should guide
research prioritization, we extracted data from the Global and National Burden of
Diseases and Injuries Among Children and Adolescents Between 1990 and 2013 study
in order to map the distribution of the burden of disease in child health to the
distribution of evidence across Review Groups in the CHFRR. RESULTS: Of the 5,520
potential Cochrane systematic reviews identified, 1,293 (23.4%) were child
relevant (an increase of 24% since 2009). Overall, these reviews included 16,738
primary studies. The most commonly represented Review Groups were Airways
(11.5%), Cystic Fibrosis and Genetic Diseases (7.9%), Acute Respiratory
Infections (7.8%), Developmental, Psychological and Learning Problems (6.7%), and
Infectious Diseases (6.2%). Corresponding authors were most often from Europe
(51%), North America (15%), and Australia (15%). The majority of systematic
reviews examined pharmacological interventions alone (52% compared to 59% in
2009). Out of 611 reviews that were assessed as up-to-date, GRADE was used in 204
(35%) reviews to assess the overall quality of the evidence, which was often
moderate (35.6%) or low (37.8%) for primary outcomes. Ninety percent of reviews
that were assessed as up to date used the Cochrane Risk of Bias tool, or a
modified version, to assess methodological quality. Most reviews conducted one or
more meta-analyses (73%). Among the 25 leading causes of death globally, the
Review Groups associated with the largest number of causes were: 1) Infectious
Diseases, 2) Anaesthesia, Critical, and Emergency Care, 3) Injuries, 4) Pregnancy
and Childbirth (PC), and 5) Neonatal. There were large discrepancies between the
number of causes of mortality that each Review Group was associated with and the
total amount of evidence each Review Group contributed to the CHFRR. Ninety-eight
percent of the causes of mortality in 2013 were from developing nations, but only
224 (17.3%) reviews had corresponding authors from developing countries.
CONCLUSION: The content and methodological characteristics of child-relevant
systematic reviews in the Cochrane CHFRR have been described in detail. There
were modest advances in methods between 2009 and 2013. Systematic reviews
contained in the CDSR offer an important resource for researcher's, clinicians
and policy makers by synthesizing an extensive body of primary research. Further
content analysis will allow the identification of clinical topics of greatest
priority for future systematic reviews in child health.
PMID- 28693464
TI - Polypoid arteriovenous malformation of the ureter mimicking a fibroepithelial
polyp, a case report.
AB - BACKGROUND: Arteriovenous malformations (AVM) of the urinary tract are extremely
rare. To the best of our knowledge, only three case of AVM of the ureter have
been described in the literature so far. CASE PRESENTATION: We present an
additional, fourth case of an AVM of the ureter, clinically presented as
asymptomatic haematuria and an obstructive process in the left ureter.
Ureteroscopic evaluation revealed a fibroepithelial polypoid-like lesion in the
proximal ureter. After biopsy showed a benign lesion, the lesion was treated with
the 2-MUm continuous wave (cw) thulium laser. Histopathological examination
revealed a polypoid laesion caused by a circumscribed arteriovenous malformation.
Almost four years after operation the patient remains asymptomatic and free of
recurrence. CONCLUSION: Arteriovenous malformations of the urinary tract are
extremely rare. We presented a fourth case of a arteriovenous malformation of the
ureter.
PMID- 28693465
TI - Involvement of Mitanins (female health volunteers) in active malaria
surveillance, determinants and challenges in tribal populated malaria endemic
villages of Chhattisgarh, India.
AB - BACKGROUND: Accredited Social Health Activists (ASHA), female health volunteers
working at village level have become an integral component of National Health
Mission (NHM) in India in the past two decades. Mitanin (meaning female friend in
local dialect), a precursor of ASHA, play an indispensable role in early
detection of health related problems and are helping in improving overall
community health status in Chhattisgarh state. The current study was carried out
to evaluate the feasibility of involving Mitanin in active malaria surveillance
work in 80 tribal villages of Chhattisgarh and to explore the challenges and
determinants to perform malaria surveillance activities by the Mitanins. METHODS:
A total of 162 Mitanins were selected and divided into two age and village
matched groups. The first group (training plus) of Mitanins were given additional
training in malaria surveillance activities in whilst the second (standard) group
received routine training. All Mitanins were interviewed using a structured
questionnaire. In-depth interviews were also conducted among randomly selected
sub groups of Mitanins (five from each group) after the completion of the
quantitative survey. Performance of Mitanins was evaluated using pre-defined
grading scores (A-E) which included various factors such as educational
qualifications and knowledge about malaria, its signs and symptoms and knowledge,
attitude and treatment practices. RESULTS: More number of Mitanins in training
plus group has showed better performance (>= B) than those in the standard group
of Mitanins (80% vs 43.5%, p = 0.001) after adjusting for socio-demographic
factors. Based on the outcome of in-depth interviews, Mitanin's lack of adequate
support from supervisors, delayed payment of incentives and lack of appreciation
were the major challenges mentioned. CONCLUSION: Mitanins can play an effective
role in active fever surveillance for malaria besides performing other health
related tasks at sub-village level after focused education on malaria related
activities and proper supervision.
PMID- 28693466
TI - The provision of generalist and specialist palliative care for patients with non
malignant respiratory disease in the North and Republic of Ireland: a qualitative
study.
AB - BACKGROUND: Previous research and key guidelines have suggested potential models
of palliative care for patients with COPD and interstitial lung disease. However,
these recommendations are often not effectively implemented in clinical practice
and are void of guidance regarding palliative care for patients with
bronchiectasis, another form of non-malignant respiratory disease. The aim of
this research was to explore generalist and specialist palliative care service
provision for people with non-malignant respiratory disease in the North and
Republic of Ireland. METHODS: Qualitative study involving a convenience sample of
17 bereaved carers and 18 healthcare professionals recruited from 2 rural and 2
urban sites on the Island of Ireland. Data collection consisted of semi
structured interviews with carers of patients with COPD, interstitial lung
disease or bronchiectasis who had died 3-18 months previously; and 4 focus groups
with healthcare professionals. Data analysed using thematic analysis. RESULTS:
Findings highlighted the lack of a clear model of holistic care delivery for
patients with non-malignant respiratory disease and illuminated the varying
levels of palliative care provision this client group experienced. Additionally,
ambiguity amongst healthcare professionals regarding prognostication illuminated
the importance of the provision of palliative care being based on patient need,
not prognosis. This research developed a potential model of palliative care which
may help healthcare professionals introduce palliative care, and specialist
respiratory care, early in the disease trajectory of non-malignant respiratory
disease, whilst also encouraging the involvement of specialist palliative care
for complex symptom management. CONCLUSION: This research provides an important
insight into a potential model of palliative care for people with non-malignant
respiratory disease, inclusive of bronchiectasis. However, the feasibility of
integrating this model into clinical practice requires further exploration.
PMID- 28693467
TI - Predicting RNA hyper-editing with a novel tool when unambiguous alignment is
impossible.
AB - BACKGROUND: Repetitive elements are now known to have relevant cellular
functions, including self-complementary sequences that form double stranded (ds)
RNA. There are numerous pathways that determine the fate of endogenous dsRNA, and
misregulation of endogenous dsRNA is a driver of autoimmune disease, particularly
in the brain. Unfortunately, the alignment of high-throughput, short-read
sequences to repeat elements poses a dilemma: Such sequences may align equally
well to multiple genomic locations. In order to differentiate repeat elements,
current alignment methods depend on sequence variation in the reference genome.
Reads are discarded when no such variations are present. However, RNA hyper
editing, a possible fate for dsRNA, introduces enough variation to distinguish
between repeats that are otherwise identical. RESULTS: To take advantage of this
variation, we developed a new algorithm, RepProfile, that simultaneously aligns
reads and predicts novel variations. RepProfile accurately aligns hyper-edited
reads that other methods discard. In particular we predict hyper-editing of
Drosophila melanogaster repeat elements in vivo at levels previously described
only in vitro, and provide validation by Sanger sequencing sixty-two individual
cloned sequences. We find that hyper-editing is concentrated in genes involved in
cell-cell communication at the synapse, including some that are associated with
neurodegeneration. We also find that hyper-editing tends to occur in short runs.
CONCLUSIONS: Previous studies of RNA hyper-editing discarded ambiguously aligned
reads, ignoring hyper-editing in long, perfect dsRNA - the perfect substrate for
hyper-editing. We provide a method that simulation and Sanger validation show
accurately predicts such RNA editing, yielding a superior picture of hyper
editing.
PMID- 28693468
TI - The self-regulated learning of medical students in the clinical environment - a
scoping review.
AB - BACKGROUND: Self-regulated learning is the individual's ability to effectively
use various strategies to reach their learning goals. We conducted this scoping
review to explore what has been found regarding self-regulated learning in the
clinical environment and how this was measured. METHODS: Using Arksey and
O'Malley's five-stage framework, we searched three medical and educational
databases as well as Google Scholar for literature on the self-regulated learning
of medical students in the clinical environment published between 1966 and
February 2017. After results were screened and relevant studies were identified,
the data was summarised and discursively reported. RESULTS: The search resulted
in 911 articles, with 14 articles included in the scoping review after the
inclusion criteria was applied. Self-regulated learning was explored in these
studies in various ways including qualitative, quantitative and mixed methods.
Three major findings were found: 1) levels of self-regulated learning change in
the clinical environment, 2) self-regulated learning is associated with academic
achievement, success in clinical skills and mental health and 3) various factors
can support self-regulated learning levels in medical students. CONCLUSIONS: Most
of articles exploring the self-regulated learning of medical students during the
clinical years have been published in the last 5 years, suggesting a growing
interest in the area. Future research could explore the self-regulated learning
levels of medical students during the clinical years using a longitudinal
approach or through the use of novel qualitative approaches.
PMID- 28693469
TI - Smoking and attitudes towards its cessation among native and international dental
students in Lithuania.
AB - BACKGROUND: Dental professionals are uniquely positioned to discourage smoking
among their patients. However, little is known about the role of cultural
background and attitudes towards smoking in the education of these professionals.
Our study aimed to compare native Lithuanian and international dental students'
smoking habits, knowledge about the harmfulness of smoking and attitudes towards
smoking cessation. METHODS: We conducted a cross-sectional survey of smoking and
its cessation among dental students at the Lithuanian University of Health
Sciences (Kaunas, Lithuania) in 2012. All Lithuanian and international dental
students in each year of dental school were invited to participate in the survey
during a compulsory practical class or seminar. Altogether 606 students
participated in the survey with a response rate of 84.2%. Explanatory factorial
analysis (EFA), multivariate Discriminant Analysis (DA) and Binary Logistic
Regression (BLR) served for the statistical analyses. RESULTS: The percentages of
occasional/current regular smokers were 41.1% and 55.7% (p = 0.068) among
Lithuanian and international male students, and 22.7% and 22.9% (p = 0.776) among
Lithuanian and international female students, respectively. The international
dental students had a deeper knowledge of the harmfulness/addictiveness of
smoking and held more positive attitudes towards smoking cessation among their
patients than did the native Lithuanian dental students. CONCLUSIONS: The
findings of the study underscored the need to properly incorporate tobacco
cessation training into the curriculum of dental education. However,
consideration of the cultural background of dental students in building up their
capacity and competence for intervening against smoking is essential.
PMID- 28693470
TI - Using the multi-objective optimization replica exchange Monte Carlo enhanced
sampling method for protein-small molecule docking.
AB - BACKGROUND: In this study, we extended the replica exchange Monte Carlo (REMC)
sampling method to protein-small molecule docking conformational prediction using
RosettaLigand. In contrast to the traditional Monte Carlo (MC) and REMC sampling
methods, these methods use multi-objective optimization Pareto front information
to facilitate the selection of replicas for exchange. RESULTS: The Pareto front
information generated to select lower energy conformations as representative
conformation structure replicas can facilitate the convergence of the available
conformational space, including available near-native structures. Furthermore,
our approach directly provides min-min scenario Pareto optimal solutions, as well
as a hybrid of the min-min and max-min scenario Pareto optimal solutions with
lower energy conformations for use as structure templates in the REMC sampling
method. These methods were validated based on a thorough analysis of a benchmark
data set containing 16 benchmark test cases. An in-depth comparison between MC,
REMC, multi-objective optimization-REMC (MO-REMC), and hybrid MO-REMC (HMO-REMC)
sampling methods was performed to illustrate the differences between the four
conformational search strategies. CONCLUSIONS: Our findings demonstrate that the
MO-REMC and HMO-REMC conformational sampling methods are powerful approaches for
obtaining protein-small molecule docking conformational predictions based on the
binding energy of complexes in RosettaLigand.
PMID- 28693471
TI - Spatial pattern analysis of nuclear migration in remodelled muscles during
Drosophila metamorphosis.
AB - BACKGROUND: Many human muscle wasting diseases are associated with abnormal
nuclear localization. During metamorphosis in Drosophila melanogaster, multi
nucleated larval dorsal abdominal muscles either undergo cell death or are
remodeled to temporary adult muscles. Muscle remodeling is associated with anti
polar nuclear migration and atrophy during early pupation followed by polar
migration and muscle growth during late pupation. Muscle remodeling is a useful
model to study genes involved in myonuclear migration. Previously, we showed that
loss of Cathepsin-L inhibited anti-polar movements, while knockdown of autophagy
related genes affected nuclear positioning along the medial axis in late
metamorphosis. RESULTS: To compare the phenotypic effects of gene perturbations
on nuclear migration more objectively, we developed new descriptors of myonuclear
distribution. To obtain nuclear pattern features, we designed an algorithm to
detect and track nuclear regions inside live muscles. Nuclear tracks were used to
distinguish between fast moving nuclei associated with fragments of dead muscles
(sarcolytes) and slow-moving nuclei inside remodelled muscles. Nuclear spatial
pattern features, such as longitudinal (lonNS) and lateral nuclear spread
(latNS), allowed us to compare nuclear migration during muscle remodelling in
different genetic backgrounds. Anti-polar migration leads to a lonNS decrease. As
expected, lack of myonuclear migration caused by the loss of Cp1 was correlated
with a significantly lower lonNS decrease. Unexpectedly, the decrease in lonNS
was significantly enhanced by Atg9, Atg5 and Atg18 silencing, indicating that the
loss of autophagy promotes the migration and clustering of nuclei. Loss of
autophagy also caused a scattering of nuclei along the lateral axis, leading to a
two-row as opposed to single row distribution in control muscles. Increased latNS
resulting from knockdown of Atg9 and Atg18 was correlated with increased muscle
diameter, suggesting that the wider muscle fibre promotes lateral displacement of
nuclei from the medial axis during polar migration. CONCLUSIONS: We developed new
nuclear features to characterize the dynamics of nuclear distribution in time
lapse images of Drosophila metamorphosis. Image quantification improved our
understanding of phenotypic abnormalities in nuclear distribution resulting from
gene perturbations. Therefore, in vivo imaging and quantitative image analysis of
Drosophila metamorphosis promise to provide novel insights into the relationship
between muscle wasting and myonuclear positioning.
PMID- 28693472
TI - Hospital staffs' perceptions of an electronic program to engage patients in
nutrition care at the bedside: a qualitative study.
AB - BACKGROUND: Advancements in technology are enabling patients to participate in
their health care through self-monitoring and self-management of diet, exercise
and chronic disease. Technologies allowing patients to participate in hospital
care are still emerging but show promise. Our team is developing a program by
which hospitalised patients can participate in their nutrition care. This study
explores hospital staffs' perceptions of using this technology to engage patients
in their care. METHODS: This qualitative study involved semi-structured
interviews with hospital staff providing routine nutrition care to patients (i.e.
dietitians, nutrition assistants, nurses, doctors and foodservice staff) from
five wards at a tertiary metropolitan teaching hospital in Australia. The
hospital currently uses an electronic foodservice system (EFS) for patient meal
ordering, accessed through personal screens at the bedside. Participants were
shown the EFS program on an iPad and asked about their perceptions of the
program, with questions from a semi-structured interview guide. Staff were
interviewed individually or in small focus groups. Interviews lasted 15-30 min
and were audio recorded and later transcribed. Data were analysed using thematic
analysis. RESULTS: Nineteen staff participated in interviews. Overall, they
expressed positive views of the EFS program and wanted it to be implemented in
practice. Their responses formed three themes, each with a number of subthemes:
1) Enacting patient participation in practice; 2) Optimising nutrition care; and
3) Considerations for implementing an EFS program in practice. Staff thought the
program would improve various aspects of nutrition care and enable patient
participation in care. Whilst they raised some concerns, they focused on
overcoming barriers and facilitating implementation if the program were to be
adopted into practice. CONCLUSIONS: Staff found an EFS program designed to engage
patients in their nutrition care acceptable, as they saw benefits to using it for
both patients and staff. Staff recognised characteristics of the program itself,
as well as allocation of roles and responsibilities in operationalising it, were
pivotal for successful implementation in practice. Their perspectives will inform
program and intervention design, and implementation and evaluation strategies.
PMID- 28693473
TI - Building COPD care on shaky ground: a mixed methods study from Swedish primary
care professional perspective.
AB - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a public health
problem. Interprofessional collaboration and health promotion interventions such
as exercise training, education, and behaviour change are cost effective, have a
good effect on health status, and are recommended in COPD treatment guidelines.
There is a gap between the guidelines and the healthcare available to people with
COPD. The aim of this study was to increase the understanding of what shapes the
provision of primary care services to people with COPD and what healthcare is
offered to them from the perspective of healthcare professionals and managers.
METHODS: The study was conducted in primary care in a Swedish county council
during January to June 2015. A qualitatively driven mixed methods design was
applied. Qualitative and quantitative findings were merged into a joint analysis.
Interviews for the qualitative component were performed with healthcare
professionals (n = 14) from two primary care centres and analysed with
qualitative content analysis. Two questionnaires were used for the quantitative
component; one was answered by senior managers or COPD nurses at primary care
centres (n = 26) in the county council and the other was answered by healthcare
professionals (n = 18) at two primary care centres. The questionnaire data were
analysed with descriptive statistics. RESULTS: The analysis gave rise to the
overarching theme building COPD care on shaky ground. This represents
professionals driven to build a supportive COPD care on 'shaky' organisational
ground in a fragmented and non-compliant healthcare organisation. The shaky
ground is further represented by uninformed patients with a complex disease,
which is surrounded with shame. The professionals are autonomous and pragmatic,
used to taking responsibility for their work, and with limited involvement of the
management. They wish to provide high quality COPD care with interprofessional
collaboration, but they lack competence and are hindered by inadequate routines
and lack of resources. CONCLUSIONS: There is a gap between COPD treatment
guidelines and the healthcare that is provided in primary care. To facilitate
implementation of the guidelines several actions are needed, such as further
training for professionals, additional resources, and improved organisational
structure for interprofessional collaboration and patient education.
PMID- 28693474
TI - Assembling metagenomes, one community at a time.
AB - BACKGROUND: Metagenomics allows unprecedented access to uncultured environmental
microorganisms. The analysis of metagenomic sequences facilitates gene prediction
and annotation, and enables the assembly of draft genomes, including uncultured
members of a community. However, while several platforms have been developed for
this critical step, there is currently no clear framework for the assembly of
metagenomic sequence data. RESULTS: To assist with selection of an appropriate
metagenome assembler we evaluated the capabilities of nine prominent assembly
tools on nine publicly-available environmental metagenomes, as well as three
simulated datasets. Overall, we found that SPAdes provided the largest contigs
and highest N50 values across 6 of the 9 environmental datasets, followed by
MEGAHIT and metaSPAdes. MEGAHIT emerged as a computationally inexpensive
alternative to SPAdes, assembling the most complex dataset using less than 500 GB
of RAM and within 10 hours. CONCLUSIONS: We found that assembler choice
ultimately depends on the scientific question, the available resources and the
bioinformatic competence of the researcher. We provide a concise workflow for the
selection of the best assembly tool.
PMID- 28693475
TI - The effect of patient death on medical students in the emergency department.
AB - BACKGROUND: The emotional consequences of patient deaths on physicians have been
studied in a variety of medical settings. Reactions to patient death include
distress, guilt, and grief. Comparatively, there are few studies on the effects
of patient death on physicians and residents in the Emergency Department (ED).
The ED setting is considered unique for having more sudden deaths that likely
include the young and previously healthy and expectations for the clinician to
return to a dynamic work environment. To date, no studies have looked at the
effects of patient deaths on the more vulnerable population of medical students
in the ED. This study examined aspects of patient deaths in the ED that most
strongly influence students' reactions while comparing it to those of an
inpatient setting. METHODS: Semi-structured qualitative interviews were carried
out with a total of 16 medical students from the American University of Beirut,
Medical Center in Lebanon who had recently encountered a patient death in the ED.
Questions included their reaction to the death, interaction with patients and
their family members, the response of the medical team, and coping mechanisms
adopted. RESULTS: The analysis revealed the following as determinant factors of
student reaction to patient death: context of death; including age of patient,
expectation of death, first death experience, relating patient death to personal
deaths, and extent of interaction with patient and family members. Importantly,
deaths in an inpatient setting were judged as more impactful than ED deaths. ED
deaths, however, were especially powerful when a trauma case was deemed
physically disturbing and cases in which family reactions were emotionally
moving. CONCLUSION: The study demonstrates that students' emotional reactions
differ as a function of the setting (surprise and shock in the ED versus sadness
and grief in an inpatient setting). Debriefing and counseling sessions on ED
deaths may benefit from this distinction.
PMID- 28693476
TI - Intended cost reduction in laparoscopic appendectomy by introducing the endoloop:
a single center experience.
AB - BACKGROUND: Cost reduction measures in medicine are gaining greater importance
nowadays, especially in high-volume procedures such as laparoscopic appendectomy
(LAE). Currently there are two common methods of dissecting the appendix from the
caecal pole: linear stapler and endoloops. The endoloop is the cheaper device but
can only be used in uncomplicated cases of appendicitis. Therefore both methods
are used in LAE depending on intraoperative findings. The goal of this study was
to retrospectively evaluate possible cost reduction due to increased use of
endoloop in LAE in our general surgery department of a tertiary referral
university hospital. METHODS: We previously used the stapler for appendix
dissection in LAE as our local protocol but introduced the endoloop as standard
method in 2015 to reduce intraoperative costs. We conducted a retrospective
analysis of patients who underwent LAE between June 2014 and October 2015 in our
department. Our purpose is to show the effects on cost reduction during the
introductory period adjusting for a potential bias due to the individual learning
curve of every surgeon. We estimated costs for LAE by taking into account average
device costs and duration of operation (DO) as well as patient outcome. RESULTS:
A total of 177 patients underwent LAE, 73 in 2014 (phase I) and 104 in 2015
(phase II). The median DO was 61 (+/- 24 SD) min during the entire period, and
increased by 14 min from phase I to II (from 51 (+/-23 SD) min to 65 (+/-24 SD)
min respectively, p < 0.001). The use of endoloops increased from 10% to 55% (p <
0.001). Patients' characteristics and outcomes did not differ significantly. A
median saving of 5.9? per operation was calculated in phase II compared to phase
I (p = 0.80). CONCLUSION: Introducing the endoloop as standard device for LAE
leads to a marginal reduction in intraoperative costs without increasing negative
outcomes. In our model the cost-reduction achieved by cheaper devices was
overcome by increased costs for DO during the initial phase of use of endoloops.
A longer follow up might show a more pronounced cost reduction.
PMID- 28693477
TI - Clinical consequences of untreated dental caries assessed using PUFA index and
its covariates in children residing in orphanages of Pakistan.
AB - BACKGROUND: The purpose of this study was to determine the prevalence and
clinical effects of untreated dental caries in Pakistani children residing in
orphanages using the DMFT and PUFA index; association of decay and untreated
dental caries with demographics including type of orphanage; behavioural and
dental visiting pattern; and association of dental pain experience and type of
orphanage with dental visiting. METHODS: A cross-sectional survey was conducted
on a total of 753 orphan children belonging to 4-17 years of age group residing
in twin cities of Rawalpindi and Islamabad, Pakistan. Clinical examination of
children was performed using the DMFT and PUFA index for the assessment of dental
caries and untreated decay, followed by questionnaire enquiring about eating and
oral hygiene habits, dental visiting pattern and dental pain and swelling
experience. Association between dental decay, child's dental visiting and pain as
a consequence of untreated decay was carried out using chi square test and
logistic regression analysis. RESULTS: The overall caries prevalence was 34.8%
and overall prevalence of PUFA/pufa was 15.9%. The mean score of DMFT and dmft
was 1.18 (SD 0.39) and 1.04 (SD 0.23), and mean PUFA was 1.18 (SD 0.57) and mean
pufa score 1.14 (SD 0.35). Untreated caries ratio was found to be 49.1%
indicating half the decay had progressed to involve the pulp. No significant
association of gender was found with DMFT, dmft, PUFA and pufa (p > 0.05),
however, when analysed individually, the 'D' component of DMFT was significantly
associated with male gender (p = 0.05). Furthermore, no significant association
of DMFT/dmft or PUFA/pufa in either dentition was found with behavioural
characteristics such as dietary and oral hygiene habits. Also, 66.2% children who
experienced pain had not been to the dentist in the past year (p = 0.013) and
52.6% children who mentioned experiencing pain at night had not been to the
dentist in the past year (p = 0.009). Children with decay were more likely to
have visited the dentist (OR 3.3, 95% CI 1.42-7.6, p = 0.006). However, children
who reported to have experienced pain were less likely to have visited the
dentist in the past year (OR 0.53, 95% CI 0.32-0.88, p = 0.014). CONCLUSIONS:
Moderate levels of decay were found in the sample with 'd' component majorly
responsible for the cumulative DMFT index. However, alarmingly almost half of the
decay component (49.1%) had progressed to involve the pulp. Experiencing pain in
teeth prompted dental visits. Initiation of preventive services for children
residing in orphanages in Pakistan would help greatly towards reducing the burden
of untreated decay.
PMID- 28693478
TI - Reliable Biomarker discovery from Metagenomic data via RegLRSD algorithm.
AB - BACKGROUND: Biomarker detection presents itself as a major means of translating
biological data into clinical applications. Due to the recent advances in high
throughput sequencing technologies, an increased number of metagenomics studies
have suggested the dysbiosis in microbial communities as potential biomarker for
certain diseases. The reproducibility of the results drawn from metagenomic data
is crucial for clinical applications and to prevent incorrect biological
conclusions. The variability in the sample size and the subjects participating in
the experiments induce diversity, which may drastically change the outcome of
biomarker detection algorithms. Therefore, a robust biomarker detection algorithm
that ensures the consistency of the results irrespective of the natural diversity
present in the samples is needed. RESULTS: Toward this end, this paper proposes a
novel Regularized Low Rank-Sparse Decomposition (RegLRSD) algorithm. RegLRSD
models the bacterial abundance data as a superposition between a sparse matrix
and a low-rank matrix, which account for the differentially and non
differentially abundant microbes, respectively. Hence, the biomarker detection
problem is cast as a matrix decomposition problem. In order to yield more
consistent and solid biological conclusions, RegLRSD incorporates the prior
knowledge that the irrelevant microbes do not exhibit significant variation
between samples belonging to different phenotypes. Moreover, an efficient
algorithm to extract the sparse matrix is proposed. Comprehensive comparisons of
RegLRSD with the state-of-the-art algorithms on three realistic datasets are
presented. The obtained results demonstrate that RegLRSD consistently outperforms
the other algorithms in terms of reproducibility performance and provides a
marker list with high classification accuracy. CONCLUSIONS: The proposed RegLRSD
algorithm for biomarker detection provides high reproducibility and
classification accuracy performance regardless of the dataset complexity and the
number of selected biomarkers. This renders RegLRSD as a reliable and powerful
tool for identifying potential metagenomic biomarkers.
PMID- 28693479
TI - Pharmacoeconomic analysis of antifungal therapy for primary treatment of invasive
candidiasis caused by Candida albicans and non-albicans Candida species.
AB - BACKGROUND: Cost-effectiveness studies of echinocandins for the treatment of
invasive candidiasis, including candidemia, are rare in Asia. No study has
determined whether echinocandins are cost-effective for both Candida albicans and
non-albicans Candida species. There have been no economic evaluations that
compare non-echinocandins with the three available echinocandins. This study was
aimed to assess the cost-effectiveness of individual echinocandins, namely
caspofungin, micafungin, and anidulafungin, versus non-echinocandins for C.
albicans and non-albicans Candida species, respectively. METHODS: A decision tree
model was constructed to assess the cost-effectiveness of echinocandins and non
echinocandins for invasive candidiasis. The probability of treatment success,
mortality rate, and adverse drug events were extracted from published clinical
trials. The cost variables (i.e., drug acquisition) were based on Taiwan's
healthcare system from the perspective of a medical payer. One-way sensitivity
analyses and probability sensitivity analyses were conducted. RESULTS: For
treating invasive candidiasis (all species), as compared to fluconazole,
micafungin and caspofungin are dominated (less effective, more expensive),
whereas anidulafungin is cost-effective (more effective, more expensive), costing
US$3666.09 for each life-year gained, which was below the implicit threshold of
the incremental cost-effectiveness ratio in Taiwan. For C. albicans,
echinocandins are cost-saving as compared to non-echinocandins. For non-albicans
Candida species, echinocandins are cost-effective as compared to non
echinocandins, costing US$652 for each life-year gained. The results were robust
over a wide range of sensitivity analyses and were most sensitive to the clinical
efficacy of antifungal treatment. CONCLUSIONS: Echinocandins, especially
anidulafungin, appear to be cost-effective for invasive candidiasis caused by C.
albicans and non-albicans Candida species in Taiwan.
PMID- 28693480
TI - Utility-preserving anonymization for health data publishing.
AB - BACKGROUND: Publishing raw electronic health records (EHRs) may be considered as
a breach of the privacy of individuals because they usually contain sensitive
information. A common practice for the privacy-preserving data publishing is to
anonymize the data before publishing, and thus satisfy privacy models such as k
anonymity. Among various anonymization techniques, generalization is the most
commonly used in medical/health data processing. Generalization inevitably causes
information loss, and thus, various methods have been proposed to reduce
information loss. However, existing generalization-based data anonymization
methods cannot avoid excessive information loss and preserve data utility.
METHODS: We propose a utility-preserving anonymization for privacy preserving
data publishing (PPDP). To preserve data utility, the proposed method comprises
three parts: (1) utility-preserving model, (2) counterfeit record insertion, (3)
catalog of the counterfeit records. We also propose an anonymization algorithm
using the proposed method. Our anonymization algorithm applies full-domain
generalization algorithm. We evaluate our method in comparison with existence
method on two aspects, information loss measured through various quality metrics
and error rate of analysis result. RESULTS: With all different types of quality
metrics, our proposed method show the lower information loss than the existing
method. In the real-world EHRs analysis, analysis results show small portion of
error between the anonymized data through the proposed method and original data.
CONCLUSIONS: We propose a new utility-preserving anonymization method and an
anonymization algorithm using the proposed method. Through experiments on various
datasets, we show that the utility of EHRs anonymized by the proposed method is
significantly better than those anonymized by previous approaches.
PMID- 28693481
TI - Psychological, situational and application-related determinants of the intention
to self-test: a factorial survey among students.
AB - BACKGROUND: The Internet enables an unprecedented opportunity to access a broad
range of self-tests (e.g. testing for HIV, cancer, hepatitis B/C), which can be
conducted by lay consumers without the help of a health professional. However,
there is only little knowledge about the determinants of the use of self-tests.
Thus, the aims of this study were (1) to experimentally investigate the impact of
situational and application-related characteristics on the intention to use a
self-test (ST), compared to being tested by a health professional at home (HPH)
or at a doctor's office (HPD), (2) to examine the applicability of social
cognitive health behaviour theories on self-testing, and (3) to explore the
advantages of integrating technological affinity into social-cognitive health
behaviour models to predict self-testing. METHODS: In a factorial survey, 1248
vignettes were rated by 208 students. The core concepts of social-cognitive
health behaviour theories, technological affinity, and different situational and
application-related characteristics were investigated. RESULTS: Intention to ST
was only predicted by the medical expertise of the tested person, while HPH and
HPD were also associated with the application purpose of the test and the
presence of an emotionally supporting person. Perceived severity and outcome
expectancy significantly predicted intention to self-test. Technological
enthusiastic people had a higher intention to use a self-test. CONCLUSIONS:
Intention to ST, HPH and HPD were predicted by different situational and
application-related characteristics. Social-cognitive health behaviour theories
can be applied to predict self-testing and do not need to be extended by
technological affinity.
PMID- 28693482
TI - The development and feasibility of a personal health-optimization system for
people with bipolar disorder.
AB - BACKGROUND: People with bipolar disorder often experience ill health and have
considerably reduced life expectancies. Suboptimal treatment is common and
includes a lack of effective medicines, overtreatment, and non-adherence to
medical interventions and lifestyle measures. E- and m-health applications
support patients in optimizing their treatment but often exhibit conceptual and
technical shortcomings. The objective of this work was to develop and test the
usability of a system targeting suboptimal treatment and compare the service to
other genres and strategies. METHODS: Based on the frameworks of shared decision
making, multi-criteria decision analysis, and single-subject research design, we
interviewed potential users, reviewed research and current approaches, and
created a first version using a rapid prototyping framework. We then iteratively
improved and expanded the service based on formative usability testing with
patients, healthcare providers, and laypeople from Norway, the UK, and Ukraine.
The evidence-based health-optimization system was developed using systematic
methods. The System Usability Scale and a questionnaire were administered in
formative and summative tests. A comparison of the system to current standards
for clinical practice guidelines and patient decision aids was performed.
RESULTS: Seventy-eight potential users identified 82 issues. Driven by user
feedback, the limited first version was developed into a more comprehensive
system. The current version encompasses 21 integrated core features, supporting 6
health-optimization strategies. One crucial feature enables patients and
clinicians to explore the likely value of treatments based on mathematical
integration of self-reported and research data and the patient's preferences. The
mean +/- SD (median) system usability score of the patient-oriented subsystem was
71 +/- 18 (73). The mean +/- SD (median) system usability score in the summative
usability testing was 78 +/- 18 (75), well above the norm score of 68. Feedback
from the questionnaire was generally positive. Eighteen out of 23 components in
the system are not required in international standards for patient decision aids
and clinical practice guidelines. CONCLUSION: We have developed the first
evidence-based health-optimization system enabling patients, clinicians, and
caregivers to collaborate in optimizing the patient's health on a shared
platform. User tests indicate that the feasibility of the system is acceptable.
PMID- 28693483
TI - Early warning signal for dengue outbreaks and identification of high risk areas
for dengue fever in Colombia using climate and non-climate datasets.
AB - BACKGROUND: Dengue has been prevalent in Colombia with high risk of outbreaks in
various locations. While the prediction of dengue epidemics will bring
significant benefits to the society, accurate forecasts have been a challenge.
Given competing health demands in Colombia, it is critical to consider the
effective use of the limited healthcare resources by identifying high risk areas
for dengue fever. METHODS: The Climate Risk Factor (CRF) index was constructed
based upon temperature, precipitation, and humidity. Considering the conditions
necessary for vector survival and transmission behavior, elevation and population
density were taken into account. An Early Warning Signal (EWS) model was
developed by estimating the elasticity of the climate risk factor function to
detect dengue epidemics. The climate risk factor index was further estimated at
the smaller geographical unit (5 km by 5 km resolution) to identify populations
at high risk. RESULTS: From January 2007 to December 2015, the Early Warning
Signal model successfully detected 75% of the total number of outbreaks 1 ~ 5
months ahead of time, 12.5% in the same month, and missed 12.5% of all outbreaks.
The climate risk factors showed that populations at high risk are concentrated in
the Western part of Colombia where more suitable climate conditions for vector
mosquitoes and the high population level were observed compared to the East.
CONCLUSIONS: This study concludes that it is possible to detect dengue outbreaks
ahead of time and identify populations at high risk for various disease
prevention activities based upon observed climate and non-climate information.
The study outcomes can be used to minimize potential societal losses by
prioritizing limited healthcare services and resources, as well as by conducting
vector control activities prior to experiencing epidemics.
PMID- 28693484
TI - Active children through individual vouchers - evaluation (ACTIVE): protocol for a
mixed method randomised control trial to increase physical activity levels in
teenagers.
AB - BACKGROUND: Many teenagers are insufficiently active despite the health benefits
of physical activity (PA). There is strong evidence to show that inactivity and
low fitness levels increase the risk of non-communicable diseases such as
coronary heart disease (CHD), type 2 diabetes and breast and colon cancers (Lee
et al. Lancet 380:219-29, 2012). A major barrier facing adolescents is
accessibility (e.g. cost and lack of local facilities). The ACTIVE project aims
to tackle this barrier through a multi-faceted intervention, giving teenagers
vouchers to spend on activities of their choice and empowering young people to
improve their fitness and PA levels. DESIGN: ACTIVE is a mixed methods randomised
control trial in 7 secondary schools in Swansea, South Wales. Quantitative and
qualitative measures including PA (cooper run test (CRT), accelerometery over 7
days), cardiovascular (CV) measures (blood pressure, pulse wave analysis) and
focus groups will be undertaken at 4 separate time points (baseline, 6 months,12
months and follow-up at 18 months). Intervention schools will receive a multi
component intervention involving 12 months of L20 vouchers to spend on physical
activities of their choice, a peer mentor scheme and opportunities to attend
advocacy meetings. Control schools are encouraged to continue usual practice. The
primary aim is to examine the effect of the intervention in improving
cardiovascular fitness. DISCUSSION: This paper describes the protocol for the
ACTIVE randomised control trial, which aims to increase fitness, physical
activity and socialisation of teenagers in Swansea, UK via a voucher scheme
combined with peer mentoring. Results can contribute to the evidence base on
teenage physical activity and, if effective, the intervention has the potential
to inform future physical activity interventions and policy. TRIAL REGISTRATION:
ISRCTN75594310 (Assigned 06/03/2017).
PMID- 28693485
TI - Three members of Medicago truncatula ST family are ubiquitous during development
and modulated by nutritional status (MtST1) and dehydration (MtST2 and MtST3).
AB - BACKGROUND: ShooT specific/Specific Tissue (ST) belong to a protein family of
unknown function characterized by the DUF2775 domain and produced in specific
taxonomic plant families, mainly Fabaceae and Asteraceae, with the Medicago
truncatula ST family being the largest. The putative roles proposed for this
family are cell elongation, biotic interactions, abiotic stress and N reserve.
The aim of this work was to go deeper into the role of three M. truncatula ST
proteins, namely ST1, ST2 and ST3. Our starting hypothesis was that each member
of the family could perform a specific role, and hence, each ST gene would be
subjected to a different type of regulation. RESULTS: The search for cis-acting
regulatory elements (CREs) in silico in pST1, pST2 and pST3 promoters showed
prevalence of tissue/organ specific motifs, especially root- and seed-specific
ones. Light, hormone, biotic and abiotic related motifs were also present. None
of these pSTs showed the same combination of CREs, or presented the same activity
pattern. In general, pST activity was associated with the vascular cylinder,
mainly in roots. Promoter activation was highly specific and dissimilar during
reproductive development. The ST1, ST2 and ST3 transcripts accumulated in most of
the organs and developmental stages analysed - decreasing with age - and
expression was higher in the roots than in the aerial parts and more abundant in
light-grown plants. The effect of the different treatments on transcript
accumulation indicated that ST1 behaved differently from ST2 and ST3, mainly in
response to several hormones and dehydration treatments (NaCl or mannitol), upon
which ST1 transcript levels decreased and ST2 and ST3 levels increased. Finally,
the ST1 protein was located in the cell wall whereas ST2 and ST3 were present
both in the cytoplasm and in the cell wall. CONCLUSIONS: The ST proteins studied
are ubiquitous proteins that could perform distinct/complementary roles in plant
biology as they are encoded by differentially regulated genes. Based on these
differences we have established two functional groups among the three STs. ST1
would participate in processes affected by nutritional status, while ST2 and ST3
seem to act when plants are challenged with abiotic stresses related to water
stress and in physiologically controlled desiccation processes such as the seed
maturation.
PMID- 28693486
TI - Performance of International Medical Students In psychosocial medicine.
AB - BACKGROUND: Particularly at the beginning of their studies, international medical
students face a number of language-related, social and intercultural challenges.
Thus, they perform poorer than their local counterparts in written and oral
examinations as well as in Objective Structured Clinical Examinations (OSCEs) in
the fields of internal medicine and surgery. It is still unknown how
international students perform in an OSCE in the field of psychosocial medicine
compared to their local fellow students. METHODS: All students (N = 1033) taking
the OSCE in the field of psychosocial medicine and an accompanying written
examination in their eighth or ninth semester between 2012 and 2015 were included
in the analysis. The OSCE consisted of four different stations, in which students
had to perform and manage a patient encounter with simulated patients suffering
from 1) post-traumatic stress disorder, 2) schizophrenia, 3) borderline
personality disorder and 4) either suicidal tendency or dementia. Students were
evaluated by trained lecturers using global checklists assessing specific
professional domains, namely building a relationship with the patient,
conversational skills, anamnesis, as well as psychopathological findings and
decision-making. RESULTS: International medical students scored significantly
poorer than their local peers (p < .001; eta2 = .042). Within the specific
professional domains assessed, they showed poorer scores, with differences in
conversational skills showing the highest effect (p < .001; eta2 = .053). No
differences emerged within the multiple-choice examination (p = .127).
CONCLUSION: International students showed poorer results in clinical-practical
exams in the field of psychosocial medicine, with conversational skills yielding
the poorest scores. However, regarding factual and practical knowledge examined
via a multiple-choice test, no differences emerged between international and
local students. These findings have decisive implications for relationship
building in the doctor-patient relationship.
PMID- 28693487
TI - Apical periodontitis associates with cardiovascular diseases: a cross-sectional
study from Sweden.
AB - BACKGROUND: Periodontal disease associates with systemic diseases but
corresponding links regarding apical periodontitis (AP) are not so clear. Hence
our aim was to study association between AP and the prevalence of systemic
diseases in a study population from Sweden. METHODS: The subjects were 150
patients from a randomly selected epidemiological sample of 1676 individuals. 120
accepted to participate and their basic and clinical examination data were
available for these secondary analyses where dental radiographs were used to
record signs for endodontic treatments and AP. Periapical Index and modified
Total Dental Index scores were calculated from the x-rays to classify the
severity of AP and dental infection burden, respectively. Demographic and
hospital record data were collected from the Swedish National Statistics Center.
T-test, chi-square and univariate analysis of covariance (ANCOVA) and regressions
analyses were used for statistics. RESULTS: Of the 120 patients 41% had AP and
61% had received endodontic treatments of which 52% were radiographically
unsatisfactory. AP patients were older and half of them were smokers. AP and
periodontitis often appeared in the same patient (32.5%). From all hospital
diagnoses, cardiovascular diseases (CVD) were most common, showing 20.4%
prevalence in AP patients. Regression analyses, controlled for age, gender,
income, smoking and periodontitis, showed AP to associate with CVD with odds
ratio 3.83 (95% confidence interval 1.18-12.40; p = 0.025). CONCLUSIONS: The
results confirmed our hypothesis by showing that AP statistically associated with
cardiovascular diseases. The finding that subjects with AP also often had
periodontitis indicates an increased oral inflammatory burden.
PMID- 28693488
TI - Donor support for quality assurance and pharmacovigilance of anti-malarials in
malaria-endemic countries.
AB - BACKGROUND: Malaria control efforts have been strengthened by funding from donor
groups and government agencies. The Global Fund to Fight AIDS, Tuberculosis and
the Malaria (Global Fund), the US President's Malaria Initiative (PMI) account
for the majority of donor support for malaria control and prevention efforts.
Pharmacovigilance (PV), which encompasses all activities relating to the
detection, assessment, understanding, and prevention of adverse effects or any
other drug-related problem, is a necessary part of efforts to reduce drug
resistance and improve treatment outcomes. This paper reports on an analysis of
PV plans in the Global Fund and PMI and World Bank's grants for malaria
prevention and control. METHODS: All active malaria grants as of September 2015
funded by the Global Fund and World Bank, and fiscal year 2015 and 2016 PMI
Malaria Operational Plans (MOP) were identified. The total amount awarded for PV
related activities and drug quality assurance was abstracted. A Key-Word-in
Context (KWIC) analysis was conducted for the content of each grant. Specific
search terms consisted of pharmacovigilance, pregn*, registry, safety, adverse
drug, mass drug administration, primaquine, counterfeit, sub-standard, and
falsified. Grants that mentioned PV activities identified in the KWIC search,
listed PV in their budgets, or included the keywords: counterfeit, sub-standard,
falsified, mass drug administration, or adverse event were thematically coded
using Dedoose software version 7.0. RESULTS: The search identified 159 active
malaria grants including 107 Global Fund grants, 39 fiscal year 2015 and 2016 PMI
grants and 13 World Bank grants. These grants were primarily awarded to low
income countries (57.2%) and in sub-Saharan Africa (SSA) (70.4%). Thirty-seven
(23.3%) grants included a budget line for PV- or drug quality assurance-related
activities, including 21 PMI grants and 16 Global Fund grants. Only 23 (14.5%)
grants directly mentioned PV. The primary focus area was improving drug quality
monitoring, especially among the PMI grants. CONCLUSIONS: The results of the
analysis demonstrate that funding for PV has not been sufficiently prioritized by
either the key malaria donor organizations or by the recipient countries, as
reflected in their grant proposal submissions and MOPs.
PMID- 28693489
TI - Inducible clindamycin and methicillin resistant Staphylococcus aureus in a
tertiary care hospital, Kathmandu, Nepal.
AB - BACKGROUND: Staphylococcus aureus, an important nosocomial pathogen, is
frequently associated with infections in human. The management of the infections
by it especially methicillin resistant ones is often difficult because
methicillin resistant S. aureus is usually resistant to multiple antibiotics.
Macrolide-lincosamide streptogramin B family of antibiotics is commonly used to
treat such infections as an alternative to vancomycin. METHODS: This study was
conducted over the period of one and half year from November 2013-April 2015 in
Microbiology laboratory of Nepal Medical College and Teaching Hospital,
Kathmandu, Nepal to find the incidence of different phenotypes of MLSB resistance
among S. aureus from clinical samples and their association with methicillin
resistance. Two hundred seventy isolates of S. aureus were included in the study.
Methicillin resistance was detected by cefoxitin disc diffusion method and
inducible clindamycin resistance by erythromycin and clindamycin disc
approximation test (D-test). RESULTS: Of the 270 clinical isolates of S. aureus,
25.1% (68/270) were MRSA. Erythromycin and clindamycin resistance was seen in
54.4% (147/270) and 41.8% (113/270) isolates respectively. Resistance to
erythromycin and clindamycin were higher in MRSA as compared to MSSA
(erythromycin-resistance: 88.2% Vs 39.1% and clindamycin-resistance: 79.4% Vs
41.8%). The overall prevalence of iMLSB and cMLSB phenotype was 11.48% (31/270)
and 29.25% (79/270) respectively. Both iMLSB and cMLSB phenotypes predominated in
MRSA strains. CONCLUSIONS: Detection rate of MRSA in our study shows the
necessity to improve in healthcare practices and to formulate new policy for the
control of MRSA infections. Clindamycin resistance in the form of iMLSB and cMLSB
especially among MRSA emphasizes the need of D-test to be performed routinely in
our set up while using clindamycin as an alternative choice to anti
staphylococcal antibiotics like vancomycin and linezolid in the treatment of
staphylococcal infections.
PMID- 28693490
TI - Intentions and experiences of effective practice in mental health specific
supported accommodation services: a qualitative interview study.
AB - BACKGROUND: Deinstitutionalisation in Europe has led to the development of
community-based accommodation for people with mental health problems. The type,
setting, and intensity of support provided vary and the costs are substantial.
Yet, despite the large investment in these services, there is little clarity on
their aims and outcomes or how they are regarded by staff and the clients.
METHODS: We interviewed 30 staff and 30 clients from the three main types of
supported accommodation in England (residential care, supported housing, floating
outreach) to explore their perspectives on the purpose of these services, and the
components of care considered most helpful. The interviews were coded and
analysed using thematic analysis. RESULTS: There were generally consistent
understandings amongst clients and staff across service types on the goals and
purposes of supported accommodation services as: building independence and
confidence; supporting people with their mental health; and providing safety and
stability. We also noted a competing theme of anxiety about the continuity of
support when clients move on from a service. Themes on the experience of what
aided effective practice centred on: the supportive presence of others;
incremental steps to progress; working together to avoid deskilling and
dependency; feeling known and personally understood; tailoring support for social
and community engagement; and building confidence through encouragement.
CONCLUSIONS: The findings provide an understanding of the commonalities in
service approach, and goals of clients in these services, as well as the
facilitators of goal attainment. However, they also highlight a common tension
between providing safe and supportive living environments, whilst also promoting
independence and facilitating rehabilitative change.
PMID- 28693491
TI - Hypoxia and hypotension in patients intubated by physician staffed helicopter
emergency medical services - a prospective observational multi-centre study.
AB - BACKGROUND: The effective treatment of airway compromise in trauma and non-trauma
patients is important. Hypoxia and hypotension are predictors of negative patient
outcomes and increased mortality, and may be important quality indicators of care
provided by emergency medical services. Excluding cardiac arrests, critical
trauma and non-trauma patients remain the two major groups to which helicopter
emergency medical services (HEMS) are dispatched. Several studies describe the
impact of pre-hospital hypoxia or hypotension on trauma patients, but few studies
compare this in trauma and non-trauma patients. The primary aim was to describe
the incidence of pre-hospital hypoxia and hypotension in the two groups receiving
pre-hospital tracheal intubation (TI) by physician-staffed HEMS. METHODS: Data
were collected prospectively over a 12-month period, using a uniform Utstein
style airway template. Twenty-one physician-staffed HEMS in Europe and Australia
participated. We compared peripheral oxygen saturation and systolic blood
pressure before and after definitive airway management. Data were analysed using
Cochran-Mantel-Haenszel methods and mixed-effects models. RESULTS: Eight hundred
forty three trauma patients and 422 non-trauma patients receiving pre-hospital TI
were included. Non-trauma patients had significantly lower predicted mean pre
intervention SpO2 compared to trauma patients. Post-intervention and admission
SpO2 for the two groups were comparable. However, 3% in both groups were still
hypoxic at admission. For hypotension, the differences between the groups were
less prominent. However, 9% of trauma and 10% of non-trauma patients were still
hypotensive at admission. There was no difference in short-term survival between
trauma (97%) and non-trauma patients (95%). Decreased level of consciousness was
the most frequent indication for TI, and was associated with increased survival
to hospital (cOR 2.8; 95% CI: 1.4-5.4). CONCLUSIONS: Our results showed that non
trauma patients had a higher incidence of hypoxia before TI than trauma patients,
but few were hypoxic at admission. The difference for hypotension was less
prominent, but one in ten patients were still hypotensive at admission. Further
investigations are needed to identify reversible causes that may be corrected to
improve haemodynamics in the pre-hospital setting. We found high survival rates
to hospital in both groups, suggesting that physician-staffed HEMS provide high
quality emergency airway management in trauma and non-trauma patients. TRIAL
REGISTRATION: Clinicaltrials.gov Identifier: NCT01502111 . Registered 22 Desember
2011.
PMID- 28693492
TI - Barriers to publishing in biomedical journals perceived by a sample of French
researchers: results of the DIAzePAM study.
AB - BACKGROUND: As publishing is essential but competitive for researchers,
difficulties in writing and submitting medical articles to biomedical journals
are disabling. The DIAzePAM (Difficultes des Auteurs a la Publication d'Articles
Medicaux) survey aimed to assess the difficulties experienced by researchers in
the AP-HP (Assistance Publique - Hopitaux de Paris, i.e., Paris Hospitals Board,
France), the largest public health institution in Europe, when preparing articles
for biomedical journals. The survey also aimed to assess researchers'
satisfaction and perceived needs. METHODS: A 39-item electronic questionnaire
based on qualitative interviews was addressed by e-mail to all researchers
registered in the AP-HP SIGAPS (Systeme d'Interrogation, de Gestion et d'Analyse
des Publications Scientifiques) bibliometric database. RESULTS: Between 28 May
and 15 June 2015, 7766 researchers should have received and read the e-mail, and
1191 anonymously completed the questionnaire (<45 years of age: 63%; women: 55%;
physician: 81%; with PhD or Habilitation a Diriger des recherches--accreditation
to direct research--: 45%). 94% of respondents had published at least one article
in the previous 2 years. 76% of respondents felt they were not publishing enough,
mainly because of lack of time to write (79%) or submit (27%), limited skills in
English (40%) or in writing (32%), and difficulty in starting writing (35%). 87%
of respondents would accept technical support, especially in English reediting
(79%), critical reediting (63%), formatting (52%), and/or writing (41%), to save
time (92%) and increase high-impact-factor journal submission and acceptance
(75%). 79% of respondents would appreciate funding support for their future
publications, for English reediting (56%), medical writing (21%), or publication
(38%) fees. They considered that this funding support could be covered by AP-HP
(73%) and/or by the added financial value obtained by their department from
previous publications (56%). CONCLUSIONS: The DIAzePAM survey highlights
difficulties experienced by researchers preparing articles for biomedical
journals, and details room for improvement.
PMID- 28693493
TI - Comparison of in-house and commercial real time-PCR based carbapenemase gene
detection methods in Enterobacteriaceae and non-fermenting gram-negative
bacterial isolates.
AB - BACKGROUND: Carbapenemase-producing gram-negative bacteria are increasing
globally and have been associated with outbreaks in hospital settings. Thus, the
accurate detection of these bacteria in infections is mandatory for administering
the adequate therapy and infection control measures. This study aimed to
establish and evaluate a multiplex real-time PCR assay for the simultaneous
detection of carbapenemase gene variants in gram-negative rods and to compare the
performance with a commercial RT-PCR assay (Check-Direct CPE). METHODS: 116
carbapenem-resistant Enterobacteriaceae, Pseudomonas aeruginosa and Acinetobacter
baumannii isolates were genotyped for carbapenemase genes by PCR and sequencing.
The defined isolates were used for the validation of the in-house RT-PCR by use
of designed primer pairs and probes. RESULTS: Among the carbapenem-resistant
isolates the genes bla KPC, bla VIM, bla NDM or bla OXA were detected. Both RT
PCR assays detected all bla KPC, bla VIM and bla NDM in the isolates. The in
house RT-PCR detected 53 of 67 (79.0%) whereas the commercial assay detected only
29 (43.3%) of the OXA genes. The in-house sufficiently distinguished the most
prevalent OXA types (23-like and 48-like) in the melting curve analysis and
direct detection of the genes from positive blood culture vials. CONCLUSION: The
Check-Direct CPE and the in-house RT-PCR assay detected the carbapenem resistance
from solid culture isolates. Moreover, the in-house assay enabled the
identification of carbapenemase genes directly from positive blood-culture vials.
However, we observed insufficient detection of various OXA genes in both assays.
Nevertheless, the in-house RT-PCR detected the majority of the OXA type genes in
Enterobacteriaceae and A. baumannii.
PMID- 28693494
TI - Variation of sentinel lymphatic channels (SLCs) and sentinel lymph nodes (SLNs)
assessed by contrast-enhanced ultrasound (CEUS) in breast cancer patients.
AB - BACKGROUND: The objective of this study was to assess the feasibility of
detecting the variation of sentinel lymphatic channels (SLCs) and sentinel lymph
nodes (SLNs) in breast cancer patients using contrast-enhanced ultrasound (CEUS).
METHODS: A total of 46 breast cancer patients were prospectively recruited in the
study. All the participants received intradermal and peritumoral injection of
microbubbles as contrast agent, and SLCs and SLNs were assessed preoperatively.
Blue dye was injected subareolarly and peritumorally during the surgery. The SLNs
detected by CEUS and blue dye were sent to the pathology laboratory for
histopathological analysis. RESULTS: At least one SLC and SLN were detected by
CEUS in all 46 cases. Three types of SLCs were detected, including superficial
sentinel lymphatic channels (SSLCs), penetrating sentinel lymphatic channels
(PSLCs), and deep sentinel lymphatic channels (DSLCs). Five lymphatic drainage
patterns (LDPs) were found, including SSLC, PSLC, SSLC + PSLC, SSLC + DSLC, and
SSLC + PSLC + DSLC. Only SSLC was detected on CEUS in 24 cases; only PSLC was
detected in 3 cases; both SSLC and PSLC were detected in 8 cases; both SSLC and
DSLC were detected in 7 cases; SSLC, PSLC, and DSLC were all detected in the
remaining 4 cases. An actual LDP was defined on the combination of CEUS and
dissection of the specimen. The accuracy rate of CEUS was 43/46. Interestingly, a
bifurcated SLC was found in 8 patients. In 3 patients, a discontinuous SLC and
non-enhanced SLN were found by CEUS. Also, no dyed SLNs were detected during the
surgery. The axillary lymph nodes turned out tumor involved histologically.
CONCLUSION: CEUS is feasible to assess the variation of SLCs and SLNs
preoperatively in breast cancer patients. SLNB is not suggested when a
discontinuous SLC and non-enhanced SLN were detected by CEUS.
PMID- 28693495
TI - An agent-based model of triple-negative breast cancer: the interplay between
chemokine receptor CCR5 expression, cancer stem cells, and hypoxia.
AB - BACKGROUND: Triple-negative breast cancer lacks estrogen, progesterone, and HER2
receptors and is thus not possible to treat with targeted therapies for these
receptors. Therefore, a greater understanding of triple-negative breast cancer is
necessary for the treatment of this cancer type. In previous work from our
laboratory, we found that chemokine ligand-receptor CCL5-CCR5 axis is important
for the metastasis of human triple-negative breast cancer cell MDA-MB-231 to the
lymph nodes and lungs, in a mouse xenograft model. We collected relevant
experimental data from our and other laboratories for numbers of cancer stem
cells, numbers of CCR5+ cells, and cell migration rates for different breast
cancer cell lines and different experimental conditions. RESULTS: Using these
experimental data we developed an in silico agent-based model of triple-negative
breast cancer that considers surface receptor CCR5-high and CCR5-low cells and
breast cancer stem cells, to predict the tumor growth rate and spatio-temporal
distribution of cells in primary tumors. We find that high cancer stem cell
percentages greatly increase tumor growth. We find that anti-stem cell treatment
decreases tumor growth but may not lead to dormancy unless all stem cells get
eliminated. We further find that hypoxia increases overall tumor growth and
treatment with a CCR5 inhibitor maraviroc slightly decreases overall tumor
growth. We also characterize 3D shapes of solid and invasive tumors using several
shape metrics. CONCLUSIONS: Breast cancer stem cells and CCR5+ cells affect the
overall growth and morphology of breast tumors. In silico drug treatments
demonstrate limited efficacy of incomplete inhibition of cancer stem cells after
which tumor growth recurs, and CCR5 inhibition causes only a slight reduction in
tumor growth.
PMID- 28693496
TI - Interaction of gamma-Fe2O3 nanoparticles with Citrus maxima leaves and the
corresponding physiological effects via foliar application.
AB - BACKGROUND: Nutrient-containing nanomaterials have been developed as fertilizers
to foster plant growth and agricultural yield through root applications. However,
if applied through leaves, how these nanomaterials, e.g. gamma-Fe2O3
nanoparticles (NPs), influence the plant growth and health are largely unknown.
This study is aimed to assess the effects of foliar-applied gamma-Fe2O3 NPs and
their ionic counterparts on plant physiology of Citrus maxima and the associated
mechanisms. RESULTS: No significant changes of chlorophyll content and root
activity were observed upon the exposure of 20-100 mg/L gamma-Fe2O3 NPs and Fe3+.
In C. maxima roots, no oxidative stress occurred under all Fe treatments. In the
shoots, 20 and 50 mg/L gamma-Fe2O3 NPs did not induce oxidative stress while 100
mg/L gamma-Fe2O3 NPs did. Furthermore, there was a positive correlation between
the dosages of gamma-Fe2O3 NPs and Fe3+ and iron accumulation in shoots. However,
the accumulated iron in shoots was not translocated down to roots. We observed
down-regulation of ferric-chelate reductase (FRO2) gene expression exposed to
gamma-Fe2O3 NPs and Fe3+ treatments. The gene expression of a Fe2+ transporter,
Nramp3, was down regulated as well under gamma-Fe2O3 NPs exposure. Although 100
mg/L gamma-Fe2O3 NPs and 20-100 mg/L Fe3+ led to higher wax content, genes
associated with wax formation (WIN1) and transport (ABCG12) were downregulated or
unchanged compared to the control. CONCLUSIONS: Our results showed that both
gamma-Fe2O3 NPs and Fe3+ exposure via foliar spray had an inconsequential effect
on plant growth, but gamma-Fe2O3 NPs can reduce nutrient loss due to their the
strong adsorption ability. C. maxima plants exposed to gamma-Fe2O3 NPs and Fe3+
were in iron-replete status. Moreover, the biosynthesis and transport of wax is a
collaborative and multigene controlled process. This study compared the various
effects of gamma-Fe2O3 NPs, Fe3+ and Fe chelate and exhibited the advantages of
NPs as a foliar fertilizer, laying the foundation for the future applications of
nutrient-containing nanomaterials in agriculture and horticulture. Graphical
abstract gamma-Fe2O3 NPs exposed on plants via foliar spray and genes associated
with the absorption and transformation of iron, as well as wax synthesis and
secretion in Citrus maxima leaves.
PMID- 28693497
TI - Inter-rater reliability of AMSTAR is dependent on the pair of reviewers.
AB - BACKGROUND: Inter-rater reliability (IRR) is mainly assessed based on only two
reviewers of unknown expertise. The aim of this paper is to examine differences
in the IRR of the Assessment of Multiple Systematic Reviews (AMSTAR) and
R(evised)-AMSTAR depending on the pair of reviewers. METHODS: Five reviewers
independently applied AMSTAR and R-AMSTAR to 16 systematic reviews (eight
Cochrane reviews and eight non-Cochrane reviews) from the field of occupational
health. Responses were dichotomized and reliability measures were calculated by
applying Holsti's method (r) and Cohen's kappa (kappa) to all potential pairs of
reviewers. Given that five reviewers participated in the study, there were ten
possible pairs of reviewers. RESULTS: Inter-rater reliability varied for AMSTAR
between r = 0.82 and r = 0.98 (median r = 0.88) using Holsti's method and kappa =
0.41 and kappa = 0.69 (median kappa = 0.52) using Cohen's kappa and for R-AMSTAR
between r = 0.77 and r = 0.89 (median r = 0.82) and kappa = 0.32 and kappa = 0.67
(median kappa = 0.45) depending on the pair of reviewers. The same pair of
reviewers yielded the highest IRR for both instruments. Pairwise Cohen's kappa
reliability measures showed a moderate correlation between AMSTAR and R-AMSTAR
(Spearman's rho =0.50). The mean inter-rater reliability for AMSTAR was highest
for item 1 (kappa = 1.00) and item 5 (kappa = 0.78), while lowest values were
found for items 3, 8, 9 and 11, which showed only fair agreement. CONCLUSIONS:
Inter-rater reliability varies widely depending on the pair of reviewers. There
may be some shortcomings associated with conducting reliability studies with only
two reviewers. Further studies should include additional reviewers and should
probably also take account of their level of expertise.
PMID- 28693498
TI - Sirolimus alters lung pathology and viral load following influenza A virus
infection.
AB - BACKGROUND: Inhibitors of mTOR, such as sirolimus, have been shown to induce
thymus involution and inflammatory lung disease in mice. The latter effect
supports the role of this serine/threonine kinase in ameliorating lung
inflammation. Other studies have shown sirolimus reduces/delays lung disease
associated with various strains of influenza A virus (IAV). Thus, the effects of
mTOR inhibitors on influenza infection deserve further studies. METHODS: Here, we
examined the changes in lung viral copies, pathology and pulmonary function
associated with IAV (A/PR/8/34) infection in mice treated with sirolimus.
RESULTS: Body weight loss peaked between days 6-11 post-infection and was more
severe in IAV-infected mice that were administered sirolimus as compared to mice
that received IAV alone (p = 0.030). Natural log viral gene copies, mean +/- SD
per mg lung tissue, in IAV-infected mice that were administered sirolimus were
17.31 +/- 1.27 on day 4, 19.31 +/- 7.46 on day 10, and 0 on day 25. The
corresponding number of copies in mice that received IAV alone were 18.56 +/-
0.95 on day 4 (p = 0.132), 1.52 +/- 1.39 on day 10 (p = 0.008), and 0 on day 25.
Lung pathology was evident on days 4, 10, and 25 post infection, with mean +/- SD
inflammatory score of 9.0 +/- 4.5 in IAV-infected mice that were administered
sirolimus, as compared to 11.5 +/- 4.5 (p = 0.335) in mice received IAV alone
(maximum score, 26.0). Impaired lung function was evident in IAV-infected mice on
days 4 and 10, as demonstrated by increased airway resistance and decreased
compliance. CONCLUSIONS: In this model, the effects of sirolimus on influenza
infection included severe weight loss and modified viral replication, respiratory
function and lung inflammation. The adverse events associated with sirolimus
treatment are consistent with its potent immunosuppressive activity and, thus,
preclude its use in IAV infection.
PMID- 28693499
TI - Conditions of gestation, childbirth and childhood associated with C-peptide in
young adults in the 1982 Birth Cohort in Pelotas-RS; Brazil.
AB - BACKGROUND: The connecting peptide in insulin has been associated with
cardiovascular risk and overall mortality in the adult population. However, its
early determinants are unknown. Assess the association of exposures during
pregnancy, delivery, and childhood with C-peptide among 22-23 years old
individuals prospectively followed since birth, in a southern Brazilian city.
METHODS: In 1982, all hospital births in the city were identified and those
livebirths whose families lived in the urban area were evaluated (n = 5914). The
1982 Pelotas Birth Cohort has prospectively followed these subjects at different
moments. In this study, we evaluated the association of C-peptide with exposures
occurring during pregnancy, delivery and childhood. In the 22-23 years follow-up
visit, we tried to follow the whole cohort and the subjects were interviewed,
examined and donated a blood sample. C-peptide was measured using the
chemiluminescence immunoassay technique (Immulite(r)-Siemens, Germany). RESULTS:
In the 22-23 years visit, 4297 subjects were interviewed and the C-peptide was
measured in 3807. The geometric mean of C-peptide was 0.83 ng/mL and the mean was
higher among women. In the adjusted analysis, C-peptide was positively associated
with family income at birth, lower among children of non-white mothers (0.90;
CI95% 0.84-0.96), higher among females (1.22; CI95% 1.16-1.28), and positively
associated with rapid weight gain between two and four years of age (1.18; CI95%
1.05-1.32). CONCLUSION: Family income at birth, non-white maternal skin color,
and rapid weight gain between two and four years of age were associated with high
levels of C-peptide.
PMID- 28693500
TI - Awareness of wearing an accelerometer does not affect physical activity in youth.
AB - BACKGROUND: This study aimed to investigate whether awareness of being monitored
by an accelerometer has an effect on physical activity in young people. METHODS:
Eighty healthy participants aged 10-18 years were randomized between blinded and
nonblinded groups. The blinded participants were informed that we were testing
the reliability of a new device for body posture assessment and these
participants did not receive any information about physical activity. In
contrast, the nonblinded participants were informed that the device was an
accelerometer that assessed physical activity levels and patterns. The
participants were instructed to wear the accelerometer for 4 consecutive days (2
school days and 2 school-free days). RESULTS: Missing data led to the exclusion
of 2 participants assigned to the blinded group. When data from the blinded group
were compared with these from the nonblinded group, no differences were found in
the duration of any of the following items: (i) wearing the accelerometer, (ii)
total physical activity, (iii) sedentary activity, and (iv) moderate-to-vigorous
activity. CONCLUSIONS: Our study shows that the awareness of wearing an
accelerometer has no influence on physical activity patterns in young people.
This study improves the understanding of physical activity assessment and
underlines the objectivity of this method. TRIAL REGISTRATION: NCT02844101
(retrospectively registered at July 13th 2016).
PMID- 28693501
TI - Knowledge and practice of immediate newborn care among health care providers in
eastern zone public health facilities, Tigray, Ethiopia, 2016.
AB - BACKGROUND: According to WHO (2013) report the number of under five-year
mortality in Ethiopia was 195,504, out of this 84,437 was from neonatal death and
this mortality is related to immediate obstetric and newborn care of babies
provided by health care providers; But little was known about the level of
knowledge and practice related to immediate newborn care and their associated
factors among health care providers generally in Tigray region and specifically
in the Eastern Zone so the aim of this study was to assess knowledge and practice
of immediate newborn care and associated factors among health care providers in
the Eastern zone public health facilities, Tigray, Ethiopia. METHODS: A cross
sectional study was conducted from December 2015 to February 2016. A total of 16
health care facilities were selected for study using simple random sampling
techniques and all health care providers in the selected health care facilities
who participated in immediate newborn care were involved in the study. Data were
entered, cleaned and analyzed using SPSS version 20.0. Ethical clearance was
obtained from Adigrat University institutional ethical review board and Tigray
regional health bureau. Consent was obtained from participants to conduct the
study. RESULT: In this study 215 participants were contacted, with a response
rate of 99.1%. Generally, from the health care providers who participated in this
study, 74.65% had adequate knowledge on newborn care and overall 72.77% of the
participants were having good newborn care practice. Among the health care
providers participated in the study, 151 (70.9%) were getting access to newborn
care national guideline and only 99 (46%) of the health care providers get
training in newborn care within the past two years before the study. Availability
of national guideline, having adequate materials, the period of taking training
and type of health facility were significant predictors for the health care
providers newborn care practice. CONCLUSION: Even though some improvement
observed in the knowledge and practice of health care providers on newborn care,
but still this study identified knowledge and practice gap. Regional health
bureau and district health offices should provide refreshment training on
immediate newborn care regularly, equipping all health facilities with necessary
materials and national guideline of newborn care and there should be sharing
experience between hospital and health center staffs working on newborn care
through mentoring.
PMID- 28693502
TI - The role of thrombectomy and diffusion-weighted imaging with MRI in post
transplant renal vein thrombosis: a case report.
AB - BACKGROUND: Surgical thrombectomy in the context of acute renal vein thrombosis
(RVT) post-transplantation has had limited success, with considerable variation
in the surgical techniques used. Unfortunately, it is usually followed by
allograft nephrectomy within a few days if rapid allograft recovery does not
ensue. We report a case of acute RVT in which nephrectomy was not performed
despite a prolonged requirement for dialysis post-thrombectomy, but with recovery
of renal function 2 weeks later. We also report the findings of serial MRI with
diffusion-weighted imaging (DW-MRI) throughout the patient's recovery, which
provided novel insights into allograft microvascular perfusion changes post
thrombectomy. CASE PRESENTATION: A 65-year old patient underwent living-unrelated
kidney transplantation complicated by acute RVT. Surgical thrombectomy and
irrigation led to a delayed, but significant, recovery of renal function. Serial
non-contrast DW-MRI scanning was used to non-invasively assess microvascular
renal blood flow post-operatively. Unlike standard Doppler ultrasonography, DW
MRI documented reduced microvascular perfusion initially, with gradual but
incomplete recovery that mirrored the partial improvement in renal function.
CONCLUSIONS: Our findings suggest that surgical thrombectomy may be more
effective than previously described if followed by careful patient observation.
Moreover, diffusion-weighted MRI appears to provide important insights into the
pathophysiology of delayed graft function and deserves further investigation.
PMID- 28693503
TI - Effectiveness of rotavirus vaccines against hospitalisations in Japan.
AB - BACKGROUND: In Japan, rotavirus hospitalisation occurs at a rate from 2.8 to 13.7
per 1000 child-years among children age less than 5 years, and it imposes a
substantial burden to the healthcare system in the country. While both monovalent
(RV1) and pentavalent (RV5) rotavirus vaccines are licensed in Japan, neither has
been incorporated in the national infant immunization programme. In this study,
we estimated vaccine effectiveness (VE) in Japan. METHODS: This study was
conducted in Yuri-Kumiai General Hospital located in a city in the north-western
part of Japan. Age-eligible children for rotavirus vaccination were enrolled if
they were hospitalized for rotavirus gastroenteritis between September 2013 and
August 2016. Rotavirus gastroenteritis was defined by the detection of rotavirus
antigen by immunochromatography. "Vaccinated" was defined as infant inoculated
with at least one dose of either RV1 or RV5. A conditional logistic regression
analysis was performed by modelling the year of birth, year of admission,
residence of the children and vaccination status, and by matching the age of
cases with that of test-negative controls. The adjusted odds ratio of the
vaccinated over unvaccinated was then used to calculate VE in the formula of (1 -
adjusted odds ratio) * 100. RESULTS: Out of the 244 patients enrolled, rotavirus
antigen was detected in 55 (22.5%) of whom 10 (18.2%) were vaccinated, whereas 94
(49.7%) of 189 test-negative controls were vaccinated. During the study period,
the vaccine uptake rate in the controls increased from 36.2% to 61.8%. On the
other hand, the vaccination coverage over the three years was 64.2% in Yuri-Honjo
city (three quarters of the catchment), and 91.4% in Nikaho city (one quarter of
the catchment). The VE was calculated to be 70.4% (95% confidence interval: 36.0
86.4%, P = 0.002). The point estimate of the VE was lower but its 95% confidence
interval overlaps those of the efficacies obtained from clinical trials in Japan.
CONCLUSION: The rotavirus vaccine was effective in the real-world setting in
Japan as in the clinical trials, and the introduction of rotavirus vaccine in the
national infant immunization schedule will substantially reduce the number of
rotavirus gastroenteritis hospitalisation in Japan.
PMID- 28693504
TI - Prevalence of multi drug resistant enteropathogenic and enteroinvasive
Escherichia coli isolated from children with and without diarrhea in Northeast
Indian population.
AB - BACKGROUND: Diarrheagenic Escherichia coli are associated with infantile diarrhea
in the developing countries. The present study was conducted to determine the
occurrence and antimicrobial resistance pattern of enteropathogenic and
enteroinvasive E. coli associated with diarrhoea among the paediatric patients.
METHODS: A total of 262 stool samples were collected from children with and
without diarrhea from Mizoram, Northeast India. E. coli were isolated and
subjected to multiplex PCR to detect virulent genes of EPEC (eaeA and bfpA) and
EIEC (ial). Isolates were subjected to antimicrobial sensitivity assay using disc
diffusion method. Selected eaeA genes were sequenced for identification and
genetic relationship. RESULTS: A total of 334 E. coli was isolated, of which
17.37% were carrying at least one virulent gene. Altogether, 14.97 and 2.40%
isolates were categorized as EPEC and EIEC, respectively. Among the DEC isolates,
4.79% were EPEC and 7.78% were EIEC. A total of 8 (2.40%) isolates were EIEC
(ial+), of which 6 (1.80%) and 2 (0.60%) were from diarrhoeic and non-diarrhoeic
patients, respectively. A total of 24 (41.40%) DEC isolates were MDR (resistance
against >=5 antimicrobials). CONCLUSIONS: A high frequency of EPEC pathotypes
associated with paediatric diarrhea was observed in Mizoram, Northeast India and
majority of the isolates are resistant to antibiotics with a high frequency of
MDR, which is a matter of concern to the public health. This also raises an alarm
to the world communities to monitor the resistance pattern and analyse in a
global scale to combat the problems of resistance development.
PMID- 28693505
TI - Effects of radiofrequency ablation versus other ablating techniques on
hepatocellular carcinomas: a systematic review and meta-analysis.
AB - BACKGROUND: Percutaneous ablation has quickly arisen as one of the important
alternative treatments for hepatocellular carcinoma (HCC). We aimed to compare
the therapeutic effects of radiofrequency ablation (RFA) and other ablative
techniques on HCCs. METHODS: Databases were searched to identify literature on
complete tumor ablation (CTA), overall survival (OS), local tumor recurrence
(LTR), and complications of RFA in the treatment of HCC, compared with those of
microwave ablation (MWA), percutaneous ethanol injection (PEI), PEI plus RFA,
cryoablation (CRA), laser ablation (LSA), and high-intensity focused ultrasound.
Randomized controlled trials and high-quality cohort studies were included in the
assessment. RESULTS: The effects of MWA and CRA appeared to be similar to those
of RFA, but lower rates of LTR and higher rates of CTA in large tumors compared
with RFA were reported (P < 0.05). CTA rates were lower in patients treated with
PEI (odds ratio [OR] 0.16, 95% confidence interval [CI] 0.06-0.42), and higher in
those treated with PEI plus RFA (OR 2.28, 95% CI 1.19-3.60), with an increased
incidence of fever (P < 0.05). LSA resulted in lower CTA rates (OR 0.32, 95% CI
0.13-0.81) and OS (hazard ratio 1.47, 95% CI 1.01-2.15), with a lower incidence
of complications. CONCLUSIONS: Compared with RFA, identical effects were found in
MWA and CRA groups. Fewer complications were observed in PEI and LSA group. PEI
plus RFA appeared more effective, with a higher rate of complications. Well
designed randomized controlled trials are further needed to confirm above
results.
PMID- 28693506
TI - Intracellular high cholesterol content disorders the clock genes, apoptosis
related genes and fibrinolytic-related genes rhythmic expressions in human plaque
derived vascular smooth muscle cells.
AB - BACKGROUND: The clock genes are involved in regulating cardiovascular functions,
and their expression disorders would lead to circadian rhythm disruptions of
clock-controlled genes (CCGs), resulting in atherosclerotic plaque formation and
rupture. Our previous study revealed the rhythmic expression of clock genes were
attenuated in human plaque-derived vascular smooth muscle cells (PVSMCs), but
failed to detect the downstream CCGs expressions and the underlying molecular
mechanism. In this study, we examined the difference of CCGs rhythmic expression
between human normal carotid VSMCs (NVSMCs) and PVSMCs. Furthermore, we compared
the cholesterol and triglycerides levels between two groups and the link to clock
genes and CCGs expressions. METHODS: Seven health donors' normal carotids and 19
carotid plaques yielded viable cultured NVSMCs and PVSMCs. The expression levels
of target genes were measured by quantitative real-time PCR and Western-blot. The
intracellular cholesterol and triglycerides levels were measured by kits. RESULT:
The circadian expressions of apoptosis-related genes and fibrinolytic-related
genes were disordered. Besides, the cholesterol levels were significant higher in
PVSMCs. After treated with cholesterol or oxidized low density lipoprotein (ox
LDL), the expressions of clock genes were inhibited; and the rhythmic expressions
of clock genes, apoptosis-related genes and fibrinolytic-related genes were
disturbed in NVSMCs, which were similar to PVSMCs. CONCLUSION: The results
suggested that intracellular high cholesterol content of PVSMCs would lead to the
disorders of clock genes and CCGs rhythmic expressions. And further studies
should be conducted to demonstrate the specific molecular mechanisms involved.
PMID- 28693507
TI - Estimating parameters for probabilistic linkage of privacy-preserved datasets.
AB - BACKGROUND: Probabilistic record linkage is a process used to bring together
person-based records from within the same dataset (de-duplication) or from
disparate datasets using pairwise comparisons and matching probabilities. The
linkage strategy and associated match probabilities are often estimated through
investigations into data quality and manual inspection. However, as privacy
preserved datasets comprise encrypted data, such methods are not possible. In
this paper, we present a method for estimating the probabilities and threshold
values for probabilistic privacy-preserved record linkage using Bloom filters.
METHODS: Our method was tested through a simulation study using synthetic data,
followed by an application using real-world administrative data. Synthetic
datasets were generated with error rates from zero to 20% error. Our method was
used to estimate parameters (probabilities and thresholds) for de-duplication
linkages. Linkage quality was determined by F-measure. Each dataset was privacy
preserved using separate Bloom filters for each field. Match probabilities were
estimated using the expectation-maximisation (EM) algorithm on the privacy
preserved data. Threshold cut-off values were determined by an extension to the
EM algorithm allowing linkage quality to be estimated for each possible
threshold. De-duplication linkages of each privacy-preserved dataset were
performed using both estimated and calculated probabilities. Linkage quality
using the F-measure at the estimated threshold values was also compared to the
highest F-measure. Three large administrative datasets were used to demonstrate
the applicability of the probability and threshold estimation technique on real
world data. RESULTS: Linkage of the synthetic datasets using the estimated
probabilities produced an F-measure that was comparable to the F-measure using
calculated probabilities, even with up to 20% error. Linkage of the
administrative datasets using estimated probabilities produced an F-measure that
was higher than the F-measure using calculated probabilities. Further, the
threshold estimation yielded results for F-measure that were only slightly below
the highest possible for those probabilities. CONCLUSIONS: The method appears
highly accurate across a spectrum of datasets with varying degrees of error. As
there are few alternatives for parameter estimation, the approach is a major step
towards providing a complete operational approach for probabilistic linkage of
privacy-preserved datasets.
PMID- 28693508
TI - Unsuccessful TB treatment outcomes with a focus on HIV co-infected cases: a cross
sectional retrospective record review in a high-burdened province of South
Africa.
AB - BACKGROUND: South Africa did not meet the MDG targets to reduce TB prevalence and
mortality by 50% by 2015, and the TB cure rate remains below the WHO target of
85%. TB incidence in the country is largely fuelled by the HIV epidemic, and co
infected patients are more likely to have unsuccessful TB treatment outcomes.
This paper analyses the demographic and clinical characteristics of new TB
patients with unsuccessful treatment outcomes, as well as factors associated with
unsuccessful treatment outcomes for HIV co-infected patients. METHODS: A cross
sectional retrospective record review of routinely collected data for new TB
cases registered in the Free State provincial electronic TB database between 2009
and 2012. The outcome variable, unsuccessful treatment, was defined as cases >=15
years that 'died', 'failed' or 'defaulted' as the recorded treatment outcome. The
data were subjected to descriptive and logistic regression analyses. RESULTS:
From 2009 to 2012 there were 66,940 new TB cases among persons >=15 years (with a
recorded TB treatment outcome), of these 61% were co-infected with HIV.
Unsuccessful TB treatment outcomes were recorded for 24.5% of co-infected cases
and 15.3% of HIV-negative cases. In 2009, co-infected cases were 2.35 times more
at risk for an unsuccessful TB treatment outcome (OR: 2.35; CI: 2.06-2.69); this
figure decreased to 1.8 times by 2012 (OR: 1.80; CI: 1.63-1.99). Among the co
infected cases, main risk factors for unsuccessful treatment outcomes were: >= 65
years (AOR: 1.71; CI: 1.25-2.35); receiving treatment in healthcare facilities in
District D (AOR: 1.15; CI 1.05-1.28); and taking CPT (and not ART) (AOR: 1.28;
CI: 1.05-1.57). Females (AOR: 0.93; CI: 0.88-0.99) and cases with a CD4 count
>350 (AOR: 0.40; CI: 0.36-0.44) were less likely to have an unsuccessful
treatment outcome. CONCLUSIONS: The importance of TB-HIV/AIDS treatment
integration is evident as co-infected patients on both ART and CPT, and those who
have a higher CD4 count are less likely to have an unsuccessful TB treatment
outcome. Furthermore, co-infected patients who require more programmatic
attention are older people and males.
PMID- 28693510
TI - Can China achieve a one-third reduction in premature mortality from non
communicable diseases by 2030?
AB - BACKGROUND: The United Nation's Sustainable Development Goals for 2030 include
reducing premature mortality from non-communicable diseases (NCDs) by one third.
To assess the feasibility of this goal in China, we projected premature mortality
in 2030 of NCDs under different risk factor reduction scenarios. METHODS: We used
China results from the Global Burden of Disease Study 2013 as empirical data for
projections. Deaths between 1990 and 2013 for cardiovascular disease (CVD),
diabetes, chronic respiratory disease, cancer, and other NCDs were extracted,
along with population numbers. We disaggregated deaths into parts attributable
and unattributable to high systolic blood pressure (SBP), smoking, high body mass
index (BMI), high total cholesterol, physical inactivity, and high fasting
glucose. Risk factor exposure and deaths by NCD category were projected to 2030.
Eight simulated scenarios were also constructed to explore how premature
mortality will be affected if the World Health Organization's targets for risk
factors reduction are achieved by 2030. RESULTS: If current trends for each risk
factor continued to 2030, the total premature deaths from NCDs would increase
from 3.11 million to 3.52 million, but the premature mortality rate would
decrease by 13.1%. In the combined scenario in which all risk factor reduction
targets are achieved, nearly one million deaths among persons 30 to 70 years old
due to NCDs would be avoided, and the one-third reduction goal would be achieved
for all NCDs combined. More specifically, the goal would be achieved for CVD and
chronic respiratory diseases, but not for cancer and diabetes. Reduction in the
prevalence of high SBP, smoking, and high BMI played an important role in
achieving the goals. CONCLUSIONS: Reaching the goal of a one-third reduction in
premature mortality from NCDs is possible by 2030 if certain targets for risk
factor intervention are reached, but more efforts are required to achieve risk
factor reduction.
PMID- 28693509
TI - Biomarkers allow detection of nutrient limitations and respective supplementation
for elimination in Pichia pastoris fed-batch cultures.
AB - BACKGROUND: Industrial processes for recombinant protein production challenge
production hosts, such as the yeast Pichia pastoris, on multiple levels. During a
common P. pastoris fed-batch process, cells experience strong adaptations to
different metabolic states or suffer from environmental stresses due to high cell
density cultivation. Additionally, recombinant protein production and nutrient
limitations are challenging in these processes. RESULTS: Pichia pastoris
producing porcine carboxypeptidase B (CpB) was cultivated in glucose or methanol
limited fed-batch mode, and the cellular response was analyzed using microarrays.
Thereby, strong transcriptional regulations in transport-, regulatory- and
metabolic processes connected to sulfur, phosphorus and nitrogen metabolism
became obvious. The induction of these genes was observed in both glucose- and
methanol- limited fed batch cultivations, but were stronger in the latter
condition. As the transcriptional pattern was indicative for nutrient
limitations, we performed fed-batch cultivations where we added the respective
nutrients and compared them to non-supplemented cultures regarding cell growth,
productivity and expression levels of selected biomarker genes. In the non
supplemented reference cultures we observed a strong increase in transcript
levels of up to 89-fold for phosphorus limitation marker genes in the late fed
batch phase. Transcript levels of sulfur limitation marker genes were up to 35
fold increased. By addition of (NH4)2SO4 or (NH4)2HPO4, respectively, we were
able to suppress the transcriptional response of the marker genes to levels
initially observed at the start of the fed batch. Additionally, supplementation
had also a positive impact on biomass generation and recombinant protein
production. Supplementation with (NH4)2SO4 led to 5% increase in biomass and 52%
higher CpB activity in the supernatant, compared to the non-supplemented
reference cultivations. In (NH4)2HPO4 supplemented cultures 9% higher biomass
concentrations and 60% more CpB activity were reached. CONCLUSIONS:
Transcriptional analysis of P. pastoris fed-batch cultivations led to the
identification of nutrient limitations in the later phases, and respective
biomarker genes for indication of limitations. Supplementation of the cultivation
media with those nutrients eliminated the limitations on the transcriptional
level, and was also shown to enhance productivity of a recombinant protein. The
biomarker genes are versatily applicable to media and process optimization
approaches, where tailor-made solutions are envisioned.
PMID- 28693511
TI - Cardiac findings in children with juvenile Dermatomyositis at disease
presentation.
AB - BACKGROUND: Juvenile Dermatomyositis (JDM) is a pediatric vasculopathy
characterized primarily by skin and muscle involvement. Cardiac findings have
been reported in children with JDM but have rarely been investigated in detail.
METHODS: We aimed to describe the relevant clinical and laboratory cardiac
findings of a cohort of patients with JDM, followed at one centre, at disease
diagnosis. RESULTS: We performed a retrospective review of 105 patients with JDM,
followed from 1991 to 2007. Six of 70 patients (9%, 6% of the entire cohort) had
abnormal electrocardiographic (ECG) findings, while 26 of 54 patients (48%, 25%
of the entire cohort) had abnormal echocardiographic (echo) findings. Many of
these findings were either mild or unlikely to be a result of JDM. CONCLUSIONS:
Our findings suggest that cardiac abnormalities at JDM disease onset are
frequently seen, but are rarely significant findings due to disease; however, JDM
patients should be considered for screening for cardiac disease as late cardiac
complications are well recognized.
PMID- 28693512
TI - A prospective, quantitative study of mental health act assessments in England
following the 2007 amendments to the 1983 act: did the changes fulfill their
promise?
AB - BACKGROUND: In 2008, the Mental Health Act (MHA) 2007 amendments to the MHA 1983
were implemented in England and Wales. The amendments were intended to remove
perceived obstacles to the detention of high risk patients with personality
disorders (PDs), sexual deviance and learning disabilities (LDs). The AMEND study
aimed to test the hypothesis that the implementation of these changes would lead
to an increase in numbers or proportions of patients with these conditions who
would be assessed and detained under the MHA 2007. METHOD: A prospective,
quantitative study of MHA assessments undertaken between July-October 2008-11 at
three English sites. Data were collected from local forms used for MHA assessment
documentation and patient electronic databases. RESULTS: The total number of
assessments in each four month period of data collection varied: 1034 in 2008,
1042 in 2009, 1242 in 2010 and 1010 in 2011 (n = 4415). Of the assessments 65.6%
resulted in detention in 2008, 71.3% in 2009, 64.7% in 2010 and 63.5% in 2011.
There was no significant change in the odds ratio of detention when comparing the
2008 assessments against the combined 2009, 2010 and 2011 data (OR = 1.025,
Fisher's exact Chi 2 p = 0.735). Only patients with LD and 'any other disorder or
disability of the mind' were significantly more likely to be assessed under the
MHA post implementation (Chi2 = 5.485, P = 0.018; Chi2 = 24.962, P > 0.001
respectively). There was no significant change post implementation in terms of
the diagnostic category of detained patients. CONCLUSIONS: In the first three
years post implementation, the 2007 Act did not facilitate the compulsory care of
patients with PDs, sexual deviance and LDs.
PMID- 28693513
TI - Multiplier method may be unreliable to predict the timing of temporary
hemiepiphysiodesis for coronal angular deformity.
AB - BACKGROUND AND PURPOSES: The multiplier method was introduced by Paley to
calculate the timing for temporary hemiepiphysiodesis. However, this method has
not been verified in terms of clinical outcome measure. We aimed to (1) predict
the rate of angular correction per year (ACPY) at the various corresponding ages
by means of multiplier method and verify the reliability based on the data from
the published studies and (2) screen out risk factors for deviation of
prediction. METHODS: A comprehensive search was performed in the following
electronic databases: Cochrane, PubMed, and EMBASETM. A total of 22 studies met
the inclusion criteria. If the actual value of ACPY from the collected date was
located out of the range of the predicted value based on the multiplier method,
it was considered as the deviation of prediction (DOP). The associations of
patient characteristics with DOP were assessed with the use of univariate
logistic regression. RESULTS: Only one article was evaluated as moderate
evidence; the remaining articles were evaluated as poor quality. The rate of DOP
was 31.82%. In the detailed individual data of included studies, the rate of DOP
was 55.44%. CONCLUSION: The multiplier method is not reliable in predicting the
timing for temporary hemiepiphysiodesis, even though it is prone to be more
reliable for the younger patients with idiopathic genu coronal deformity.
PMID- 28693514
TI - Disparities in dietary intake and physical activity patterns across the
urbanization divide in the Peruvian Andes.
AB - BACKGROUND: Diet and activity are thought to worsen with urbanization, thereby
increasing risk of obesity and chronic diseases. A better understanding of
dietary and activity patterns across the urbanization divide may help identify
pathways, and therefore intervention targets, leading to the epidemic of
overweight seen in low- and middle-income populations. Therefore, we sought to
characterize diet and activity in a population-based study of urban and rural
residents in Puno, Peru. METHODS: We compared diet and activity in 1005 (503
urban, 502 rural) participants via a lifestyle questionnaire. We then recruited
an age- and sex-stratified random sample of 50 (25 urban, 25 rural) participants
to further characterize diet and activity. Among these participants, diet
composition and macronutrient intake was assessed by three non-consecutive 24-h
dietary recalls and physical activity was assessed using Omron JH-720itc
pedometers. RESULTS: Among 1005 participants, we found that urban residents
consumed protein-rich foods, refined grains, sugary items, and fresh produce more
frequently than rural residents. Among the 50 subsample participants, urban
dwellers consumed more protein (47 vs. 39 g; p = 0.05), more carbohydrates (280
vs. 220 g; p = 0.03), more sugary foods (98 vs. 48 g, p = 0.02) and had greater
dietary diversity (6.4 vs 5.8; p = 0.04). Rural subsample participants consumed
more added salt (3.1 vs 1.7 g, p = 0.006) and tended to consume more vegetable
oil. As estimated by pedometers, urban subsample participants burned fewer
calories per day (191 vs 270 kcal, p = 0.03). CONCLUSIONS: Although urbanization
is typically thought to increase consumption of fat, sugar and salt, our 24-h
recall results were mixed and showed lower levels of obesity in rural Puno were
not necessarily indicative of nutritionally-balanced diets. All subsample
participants had relatively traditional lifestyles (low fat intake, limited
consumption of processed foods and frequent walking) that may play a role in
chronic disease outcomes in this region.
PMID- 28693515
TI - Communication about uncertainty and hope: A randomized controlled trial assessing
the efficacy of a communication skills training program for physicians caring for
cancer patients.
AB - BACKGROUND: Although previous studies have reported the efficacy of communication
skills training (CST) programs, specific training addressing communication about
uncertainty and hope in oncology has not yet been studied. This paper describes
the study protocol of a randomized controlled trial assessing the efficacy of a
CST program aimed at improving physician ability to communicate about uncertainty
and hope in encounters with cancer patients. METHODS/DESIGN: Physician
participants will be randomly assigned in groups (n = 3/group) to a 30-h CST
program (experimental group) or to a waiting list (control group). The training
program will include learner-centered, skills-focused, practice-oriented
techniques. Training efficacy is assessed in the context of an encounter with a
simulated advanced stage cancer patient at baseline and after the CST for the
experimental group, and after four months for the waiting-list group. Efficacy
assessments will include communicational, psychological and physiological
measures. Group-by-time effects will be analyzed using a generalized estimating
equation (GEE). A power analysis indicated that a sample size of 60 (30
experimental and 30 control) participants will be sufficient to detect effects.
DISCUSSION: The current study will aid in the development of effective CST
programs to improve physician ability to communicate about uncertainty and hope
in encounters with cancer patients. TRIAL REGISTRATION: US Clinical Trials
Register NCT02836197 .
PMID- 28693516
TI - Pancreatic metastasis from invasive pleomorphic lobular carcinoma of the breast:
a rare case report.
AB - BACKGROUND: Invasive pleomorphic lobular carcinoma (PLC) is an aggressive subtype
of invasive lobular carcinoma of the breast, which has its own histopathological
and biological features. The metastatic patterns for PLC are distinct from those
of invasive ductal carcinoma. In addition, pancreatic metastasis from PLC is
extremely rare. CASE PRESENTATION: We report a rare case of a 48-year-old woman
presenting with clinical gastrointestinal symptoms and pancreatic metastasis of
PLC. The pancreatic tumor was composed of pleomorphic tumor cells arranged in the
form of solid sheets and nests and as single files, with frequent mitotic
figures, nucleolar prominence, high nuclear to cytoplasmic ratio and loss of
cohesion. The malignant cells were positive for p120 (cytoplasmic) and GATA3 and
negative for estrogen receptor, progesterone receptor, human epidermal growth
factor receptor 2, E-cadherin, gross cystic disease fluid protein 15 and
mammaglobin, which indicated a lobular carcinoma phenotype of the breast.
CONCLUSIONS: To the best of our knowledge, this is one of the few reported cases
in the literature of pancreatic metastasis of invasive lobular carcinoma of the
breast, of which the definitive diagnosis was obtained only after surgery. Rare
metastasis sites should be considered, particularly, when a patient has a medical
history of PLC.
PMID- 28693517
TI - JMJD2A promotes the Warburg effect and nasopharyngeal carcinoma progression by
transactivating LDHA expression.
AB - BACKGROUND: Jumonji C domain 2A (JMJD2A), as a histone demethylases, plays a
vital role in tumorigenesis and progression. But, its functions and underlying
mechanisms of JMJD2A in nasopharyngeal carcinoma (NPC) metabolism are remained to
be clarified. In this study, we investigated glycolysis regulation by JMJD2A in
NPC and the possible mechanism. METHODS: JMJD2A expression was detected by
Western blotting and Reverse transcription quantitative real-time PCR analysis.
Then, we knocked down and ectopically expressed JMJD2A to detect changes in
glycolytic enzymes. We also evaluated the impacts of JMJD2A-lactate dehydrogenase
A (LDHA) signaling on NPC cell proliferation, migration and invasion. ChIP assays
were used to test whether JMJD2A bound to the LDHA promoter. Finally, IHC was
used to verify JMJD2A and LDHA expression in NPC tissue samples and analyze their
correlation between expression and clinical features. RESULTS: JMJD2A was
expressed at high levels in NPC tumor tissues and cell lines. Both JMJD2A and
LDHA expression were positively correlated with the tumor stage, metastasis and
clinical stage. Additionally, the level of JMJD2A was positively correlated with
LDHA expression in NPC patients, and higher JMJD2A and LDHA expression predicted
a worse prognosis. JMJD2A alteration did not influence most of glycolytic enzymes
expression, with the exception of PFK-L, PGAM-1, LDHB and LDHA, and LDHA
exhibited the greatest decrease in expression. JMJD2A silencing decreased LDHA
expression and the intracellular ATP level and increased LDH activity, lactate
production and glucose utilization, while JMJD2A overexpression produced the
opposite results. Furthermore, JMJD2A could combine to LDHA promoter region and
regulate LDHA expression at the level of transcription. Activated JMJD2A-LDHA
signaling pathway promoted NPC cell proliferation, migration and invasion.
CONCLUSIONS: JMJD2A regulated aerobic glycolysis by regulating LDHA expression.
Therefore, the novel JMJD2A-LDHA signaling pathway could contribute to the
Warburg effects in NPC progression.
PMID- 28693518
TI - The third delay: understanding waiting time for obstetric referrals at a large
regional hospital in Ghana.
AB - BACKGROUND: Delay in receiving care significantly contributes to maternal
morbidity and mortality. Much has been studied about reducing delays prior to
arrival to referral facilities, but the delays incurred upon arrival to the
hospital have not been described in many low- and middle-income countries.
METHODS: We report on the obstetric referral process at Ridge Regional Hospital,
Accra, Ghana, the largest referral hospital in the Ghana Health System. This
study uses data from a prospectively-collected cohort of 1082 women presenting
with pregnancy complications over a 10-week period. To characterize which factors
lead to delays in receiving care, we analyzed wait times based on reason for
referral, time and day of arrival, and concurrent volume of patients in the
triage area. RESULTS: The findings show that 108 facilities refer patients to
Ridge Regional Hospital, and 52 facilities account for 90.5% of all transfers.
The most common reason for referral was fetal-pelvic size disproportion (24.3%)
followed by hypertensive disorders of pregnancy (9.8%) and prior uterine scar
(9.1%). The median arrival-to-evaluation (wait) time was 40 min (IQR 15-100); 206
(22%) of women were evaluated within 10 min of arrival. Factors associated with
longer wait times include presenting during the night shift, being in latent
labour, and having a non-time-sensitive risk factor. The median time to be
evaluated was 32 min (12-80) for women with hypertensive disorders of pregnancy
and 37 min (10-66) for women with obstetric hemorrhage. In addition, the wait
time for women in the second stage of labour was 30 min (12-79). CONCLUSIONS:
Reducing delay upon arrival is imperative to improve the care at high-volume
comprehensive emergency obstetric centers. Although women with time-sensitive
risk factors such as hypertension, bleeding, fever, and second stage of labour
were seen more quickly than the baseline population, all groups failed to be
evaluated within the international standard of 10 min. This study emphasizes the
need to improve hospital systems so that space and personnel are available to
access high-risk pregnancy transfers rapidly.
PMID- 28693519
TI - Tracing the natural course of visual acuity and quality of life in neovascular
age-related macular degeneration: a systematic review and quality of life study.
AB - BACKGROUND: Describing the natural course of neovascular age-related macular
degeneration (nAMD) is essential in discussing prognosis and treatment options
with patients and to support cost-effectiveness studies. METHODS: First, we
performed a literature search in PubMed, Embase, and Cochrane. We included
randomized clinical trials and prospective observational studies reporting visual
acuity (VA) in non-treated patients, 24 studies in total. We integrated VA data
using best fit on Lineweaver-Burke plots and modelled with non-linear regression
using reciprocal terms. Second, we performed a quality-of-life (QoL) study in
nAMD patients. We measured VA with Radner reading charts and QoL with the Health
Utilities Index issue 3 (HUI-3) questionnaire in 184 participants. We studied the
relation VA-QoL with linear regression. Third, with Monte Carlo simulation, we
integrated the VA model from the literature review and the relation VA-QoL from
the QoL study. RESULTS: Visual acuity was 0.4 and 0.07 after 5 years in the
better-seeing, and worse-seeing eye, respectively. After 4.3 years, VA was <0.5
in the better-seeing eye; <0.3 after 7 years; 0.05 after 17 years. QoL score
decreased from 0.6 to 0.45 after 10 years. CONCLUSIONS: The natural course of
nAMD in both eyes needs to be considered when informing patients. Visual acuity
in the best eye decreases to below 0.5 in 4.3 years. This affects QoL
significantly.
PMID- 28693520
TI - Strengthening primary health care teams with palliative care leaders: protocol
for a cluster randomized clinical trial.
AB - BACKGROUND: The objective of the Balearic Islands Palliative Care (PC) Program is
to improve the quality of PC through a shared model consisting of primary health
care professionals, home-based PC teams, and PC units in hospitals. According to
the World Health Organization (WHO), patients with advanced cancer and other
terminal diseases benefit from early identification and proactive PC. We will
evaluate the effectiveness of an intervention in which a PC leader is established
in the primary health care center, and assess the effect of this intervention on
the early identification of patients in need of PC, the efficient use of health
care services, and direct health care costs. METHODS: Design: A two-arm cluster
randomized clinical trial of 30 Primary Health Care Centers (PHCC) in Mallorca
(Spain), in which each center was randomized to an intervention arm or a usual
care arm. We expect that the number of patients identified as suitable for PC
(including non-oncological PC) is at least 5% greater in the intervention arm.
SAMPLE SIZE: A total of 4640 deceased patients. Outcomes will be assessed by a
blinded external review of the electronic records. INTERVENTIONS: General
practitioners (GPs) and nurse leaders in PC for each PHCC will be appointed.
These leaders will help promote PC training of colleagues, improve symptom
management and psychological support of patients, and evaluate the complexity of
individual cases so that these cases receive assistance from PC home-based teams.
MEASUREMENTS: Early identification (>90 days before death), evaluation of case
complexity, level of case complexity (with referral to a home-based PC team), use
and cost of hospital and primary care services, and quality of life during the
last month of life (>=2 emergency room visits, >=2 hospital admissions, >=14 days
of hospitalization). DISCUSION: PC leaders in primary care teams will improve the
early identification of patients eligible for PC. This initiative could improve
the quality of end-of-life care and utilization of hospital resources. TRIAL
REGISTRATION: ISRCTN Registry identifier: ISRCTN92479122 . Retrospectively
registered on 28 February 2017.
PMID- 28693521
TI - Predictors of intensive care unit admission and mortality in patients with
ischemic stroke: investigating the effects of a pulmonary rehabilitation program.
AB - BACKGROUND: The aim of this study was to investigate the predictors of intensive
care unit (ICU) admission and mortality among stroke patients and the effects of
a pulmonary rehabilitation program on stroke patients. METHODS: This prospective
study enrolled 181 acute ischemic stroke patients aged between 40 and 90 years.
Demographical characteristics, laboratory tests, diffusion-weighed magnetic
resonance imaging (DWI-MRI) time, nutritional status, vascular risk factors,
National Institute of Health Stroke Scale (NIHSS) scores and modified Rankin
scale (MRS) scores were recorded for all patients. One-hundred patients
participated in the pulmonary rehabilitation program, 81 of whom served as a
control group. RESULTS: Statistically, one- and three-month mortality was
associated with NIHSS and MRS scores at admission and three months (p<0.001;
r=0.440, r=0.432, r=0.339 and r=0.410, respectively). One and three months
mortality- ICU admission had a statistically significant relationship with
parenteral nutrition (p<0.001; r=0.346, r=0.300, respectively; r=0.294 and
r=0.294, respectively). Similarly, there was also a statistically significant
relationship between pneumonia onset and one- and three-month mortality- ICU
admission (p<0.05; r=0.217, r=0.127, r=0.185 and r=0.185, respectively). A
regression analysis showed that parenteral nutrition (odds ratio [OR] =13.434,
95% confidence interval [CI] =1.148-157.265, p=0.038) was a significant predictor
of ICU admission. The relationship between pulmonary physiotherapy (PPT) and ICU
admission- pneumonia onset at the end of three months was statistically
significant (p=0.04 and p=0.043, respectively). CONCLUSION: This study showed
that PPT improved the prognosis of ischemic stroke patients. We believe that a
pulmonary rehabilitation program, in addition to general stroke rehabilitation
programs, can play a critical role in improving survival and functional outcomes.
TRIAL REGISTRATION: NCT03195907 . Trial registration date: 21.06.2017
'Retrospectively registered'.
PMID- 28693522
TI - Erratum to: Supplemental vibrotactile feedback control of stabilization and
reaching actions of the arm using limb state and position error encodings.
PMID- 28693523
TI - Inhibition of LIN28B impairs leukemia cell growth and metabolism in acute myeloid
leukemia.
AB - BACKGROUND: Current conventional chemotherapy for acute myeloid leukemia (AML)
can achieve remission in over 70% of patients, but a majority of them will
relapse within 5 years despite continued treatment. The relapse is postulated to
be due to leukemia stem cells (LSCs), which are different from normal
hematopoietic stem cells (HSCs). LIN28B is microRNA regulator and stem cell
reprogramming factor. Overexpression of LIN28B has been associated with advance
human malignancies and cancer stem cells (CSCs), including AML. However, the
molecular mechanism by which LIN28B contributes to the development of AML remains
largely elusive. METHODS: We modulated LIN28B expression in AML and non-leukemic
cells and investigated functional consequences in cell proliferation, cell cycle,
and colony-forming assays. We performed a microarray-based analysis for LIN28B
silencing cells and interrogated gene expression data with different
bioinformatic tools. AML mouse xenograft model was used to examine the in vivo
function of LIN28B. RESULTS: We demonstrated that targeting LIN28B in AML cells
resulted in cell cycle arrest, inhibition of cell proliferation and colony
formation, which was induced by de-repression of let-7a miRNA. On the other hand,
overexpression of LIN28B promoted cell proliferation. Data point to a mechanism
where that inhibition of LIN28B induces metabolic changes in AML cells. IGF2BP1
was confirmed to be a novel downstream target of LIN28B via let-7 miRNA in AML.
Notably, ectopic expression of LIN28B increased tumorigenicity, while silencing
LIN28B led to slow tumor growth in vivo. CONCLUSIONS: In sum, these results
uncover a novel mechanism of an important regulatory signaling, LIN28B/let
7/IGF2BP1, in leukemogenesis and provide a rationale to target this pathway as
effective therapeutic strategy.
PMID- 28693524
TI - National consensus on communication in prehospital trauma care, the DENIM study.
AB - BACKGROUND: In the Netherlands prehospital trauma care is provided by emergency
medical services (EMS) nurses. This care is extended by Physician staffed
Helicopter Emergency Medical Services (P-HEMS) for the more severely injured
patient. Prehospital communication is a factor of influence on the identification
of these patients and the dispatch of P-HEMS. Though prehospital communication it
is often perceived to be incomplete and unstructured. To elucidated factors of
influence on prehospital triage and the identification of the severely injured
patient a Delphi study was performed. METHODS: A three round modified Delphi
study was designed to explore concepts amongst experts in prehospital trauma
care. P-HEMS physicians/nurses, trauma surgeons, EMS nurses and dispatch center
operators where asked to state their opinion regarding identification of the poly
trauma patient, trauma patient characteristics, prehospital communication and
prehospital handover. RESULTS: Seventy-one panellist completed all three rounds.
For the first round seven cases and 13 theses were presented. From the
answers/argumentation the second round was build, in which 68 theses had to be
ranked within four principle themes: factors that influence prehospital
communication, critical information for proper handover, factors influencing
collaboration and how training/education can influence this. Out of these answers
the third survey was build, focussing on determining the exact content of a
prehospital trauma handover. The majority of the panellists agreed to a set of
parameters resulting in a new model of inter-professional hand over regarding
prehospital trauma patients. DISCUSSION: Exact identification of the poly trauma
patient in need of care by P-HEMS is difficult though prehospital communication
and the prehospital handover may be improved. CONCLUSION: The respondents report
that prehospital communication needs to be unambiguous to improve trauma care.
Consensus was reached on a set of ten parameters that should minimally be handed
over with regard to a prehospital trauma patient. This to facilitate prehospital
communication between the Dispatch centre, EMS, P-HEMS and the receiving
hospital.
PMID- 28693525
TI - Baseline characteristics of study sites and women enrolled in a three-arm cluster
randomized controlled trial: PMTCT uptake and retention (pure) Malawi.
AB - BACKGROUND: Malawi introduced an ambitious public health program known as "Option
B+" which provides all HIV-infected pregnant and breastfeeding women with
lifelong combination antiretroviral therapy, regardless of WHO clinical stage or
CD4 cell count. The PMTCT Uptake and REtention (PURE) study aimed at evaluating
the effect of peer-support on care-seeking and retention in care. METHODS/DESIGN:
PURE Malawi was a three-arm cluster randomized controlled trial that compared
facility-based and community-based models of peer support to standard of care
under Option B+ strategy. Each arm was expected to enroll a minimum of 360 women
with a total minimum sample size of 1080 participants. 21 sites (clusters) were
selected for inclusion in the study. This paper describes the site selection,
recruitment, enrollment process and baseline characteristics of study sites and
women enrolled in the trial. RESULTS: Study implementation was managed by 3
partner organizations; each responsible for 7 study sites. The trial was
conducted in the South East, South West, and Central West zones of Malawi, the
zones where the implementing partners operate. Study sites included 2 district
hospitals, 2 mission hospitals, 2 rural hospitals, 13 health centers and 1
private clinic. Enrollment occurred from November 2013 to November 2014, over a
median period of 31 weeks (range 17-51) by site. A total of 1269 HIV-infected
pregnant (1094) and breastfeeding (175) women, who were eligible to initiate ART
under Option B+, were enrolled. Each site reached or surpassed the minimum sample
size. Comparing the number of women enrolled versus antenatal cohort reports,
sites recruited a median of 90% (IQR 75-100) of eligible reported women. In the
majority of sites the ratio of pregnant and lactating women enrolled in the study
was similar to the ratio of reported pregnant and lactating women starting ART in
the same sites. The median age of all women was 27 (IQR 22-31) years. All women
have >=20 months of possible follow-up time; 96% >= 2 years (24-32 months).
CONCLUSION: The PURE Malawi study showed that 3 implementing partner
organizations could successfully recruit a complex cohort of pregnant and
lactating women across 3 geographical zones in Malawi within a reasonable
timeline. TRIAL REGISTRATION: This study is registered at clinicaltrials.gov - ID
Number NCT02005835 . Registered 4 December, 2013.
PMID- 28693526
TI - Height, weight and body mass index of children with congenital cataracts before
surgical treatment.
AB - BACKGROUND: To investigate the distribution of the height, weight and body mass
index (BMI) of children with congenital cataracts (CC) before surgical treatment.
METHODS: This prospective study included children with CC <=14 years of age
presenting at the Zhongshan Ophthalmic Center from Jan. 2013 to Aug. 2016. The
height, weight, and BMI measurements of all participating children were obtained
and compared with the World Health Organization Child Growth Reference (WHO
Reference), matched by age and gender. The presence of a family history of CC or
complicated systemic diseases as well as parental education levels and family
income were also recorded. RESULTS: In total, 595 children with CC were included.
The mean age was 52.75 +/- 33.99 months, and 34.29% (204/595) of them were
unilateral cases. Among all of the children, 6.72% (40/595) of cases were
complicated by systemic diseases. More than 1/5 (21.01%, 125/595) of the children
had a family history of CC and exhibited bilateral involvement. Less than 1/4
(23.2) of the mothers were highly educated, and more than half of the families
had a family income below the city average. Height, weight, and BMI measurements
of most children with CC were within the normal ranges (+/-95% CI of the WHO
Reference). Compared to the WHO Reference, both girls and boys aged 2-5 years
revealed shorter heights, and the girls aged 5-14 years exhibited a shorter
height, lower body weight and lower BMI. The heights of the children with CC and
systemic diseases were also shorter than the WHO Reference. The children with CC
who had a family history of disease had shorter heights and lower BMIs than
children with CC but no family history, and the measurements of both groups were
lower than the WHO Reference values. CONCLUSIONS: The height, weight and BMI of
most of the children with CC in this study were within the normal ranges of the
WHO Reference. However, the children with CC and concomitant systemic diseases
and those with a family history of CC had shorter heights and lower BMIs. This
information aids in our understanding of the physical development of children
with CC.
PMID- 28693527
TI - Social workers' involvement in advance care planning: a systematic narrative
review.
AB - BACKGROUND: Advance care planning is a process of discussion that enables
competent adults to express their wishes about end-of-life care through periods
of decisional incapacity. Although a number of studies have documented social
workers' attitudes toward, knowledge about, and involvement in advance care
planning, the information is fragmented. The purpose of this review was to
provide a narrative synthesis of evidence on social workers' perspectives and
experiences regarding implementation of advance care planning. METHODS: Six
databases were searched for peer-reviewed research papers from their respective
inception through December 2016. All of the resulting studies relevant to both
advance care planning and social worker were examined. The findings of relevant
studies were synthesized thematically. RESULTS: Thirty-one articles met the
eligibility criteria. Six research themes were identified: social workers'
attitudes toward advance care planning; social workers' knowledge, education and
training regarding advance care planning; social workers' involvement in advance
care planning; social workers' perceptions of their roles; ethical issues
relevant to advance care planning; and the effect of social work intervention on
advance care planning engagement. The findings suggest that there is a consensus
among social workers that advance care planning is their duty and responsibility
and that social workers play an important role in promoting and implementing
advance care planning through an array of activities. CONCLUSIONS: This study
provides useful knowledge for implementing advance care planning through
illustrating social workers' perspectives and experiences. Further studies are
warranted to understand the complexity inherent in social workers' involvement in
advance care planning for different life-limiting illnesses or within different
socio-cultural contexts.
PMID- 28693528
TI - Impact of oocytes with CLCG on ICSI outcomes and their potential relation to
pesticide exposure.
AB - BACKGROUND: Oocyte quality is a key limiting factor in female fertility which is
primarily reflected in morphological features. Centrally located cytoplasm
granulation (CLCG) is one type of cytoplasmic dimorphism exhibited by oocytes
that could be linked to pesticide exposure with a significant risk of decreased
ICSI outcomes. METHODS: This retrospective study included 633 women who were part
of an intracytoplasmic spermatozoa injection (ICSI) program between 2009 and
2011. The participants lived in the Picardy region of France and had been exposed
to pesticides. The participants were divided in two groups based on prevalence of
oocytes with CLCG (LCLCG [n = 83]: low prevalence of oocytes with CLCG under 25%.
HCLCG [n = 68]: high prevalence of CLCG over 75%). The embryological and clinical
outcomes were analysed for both groups and were calculated using the difference
between the two values. RESULTS: Results for couples with HCLCG compared to LCLCG
showed a decrease in embryo cleavage, ongoing pregnancy, and live birth rates
(82%, 14%, 13% vs 99%, 32%, 30%, respectively).The early miscarriage rate was
increased (47% vs 11%), with an OR of 3.1 (95%CI [2.1-4.1]). Due to high
pesticide exposure (over 3000 g/ha), there is a higher risk of a resulting
disturbed oocyte cohort with a high prevalence of CLCG over 75%. CONCLUSION: The
high prevalence of oocytes with CLCG over 75% has a negative effect on embryos
and the general ICSI clinical outcomes. Furthermore, a putative association
between pesticide exposure and risk of CLCG was identified, justifying the need
for further research and a potential need to find alternative assisted
reproductive technologies for these couples. TRIAL REGISTRATION: Tabacfertimasc.
ID number: ID2011-A00634-37 ; registered 2011/2/8.
PMID- 28693529
TI - Waterpipe and cigarette tobacco smoking among Palestinian university students: a
cross-sectional study.
AB - BACKGROUND: During the last two decades, waterpipe tobacco smoking (WTS), also
known as hookah, witnessed a global increase in use, especially among youth.
Little information is known about the burden of WTS among Palestinian youth. A
cross-sectional study was conducted to estimate the prevalence of WTS and
cigarette smoking and explore the associated factors among a sample of
Palestinian university students. METHODS: 1891 students, from five Palestinian
universities in the West Bank and Gaza Strip, completed a self-administered, web
based survey in 2014-2015. The questionnaire, which was based on the Global
Adults Tobacco Survey (GATS), had questions on WTS and cigarette smoking patterns
and socio-demographic and university-related characteristics. Binary logistic
regression analyses were computed to investigate associated factors with WTS and
cigarette smoking. RESULTS: 50.9% of the sample was women. The mean age was 20.1
+/- 2.0. Overall, 30.0% of participants were current tobacco smokers and 33.4%
reported ever smoking tobacco through a waterpipe. The prevalence of current WTS
(24.4%) surpassed the prevalence of current cigarette smoking (18.0%), with a
significantly higher prevalence among men compared to women. The gender gap for
WTS (36.4% vs. 12.9%) was smaller than that for cigarette smoking (32.8% vs.
3.6%). Binary logistic regression models for the total sample (men and women)
revealed that men were more likely to be current waterpipe and cigarette tobacco
smokers compared to women (AOR = 4.20, 95% CI = 3.22-5.48, and AOR = 10.91, 95%
CI = 7.25-16.42, respectively). Geographic area of residence, faculty of study
and self-reported academic achievement were also associated with the likelihood
of being current waterpipe and cigarette tobacco smokers. CONCLUSION: A high
prevalence of WTS was reported among our study sample, and it surpassed the
prevalence of cigarette smoking. Interventions to curb the practice of tobacco
smoking among Palestinian youth should be tailored differently to WTS and
cigarette smoking, be gender-sensitive and specific and target the regional
variation in the smoking behavior.
PMID- 28693530
TI - Analysis of circulating microRNAs in patients with repaired Tetralogy of Fallot
with and without heart failure.
AB - BACKGROUND: MicroRNAs (miRNAs) are a class of regulatory RNAs that regulate gene
expression post-transcriptionally. Little, however, is known on the expression
profile of circulating miRNAs in Tetralogy of Fallot (TOF) patients late after
surgical repair. In this study, we aimed to identify the specific patterns of
circulating miRNAs in blood of patients with repaired, non-syndromic TOF and to
assess whether these specific miRNAs may be useful to differentiate patients with
and without heart failure. METHODS: SurePrintTM 8 * 60 K Human v16 miRNA arrays
were used to determine miRNA expression profiles in 15 healthy controls and 37
patients after TOF repair of whom 3 had symptomatic right heart failure. The
expression levels of selected miRNAs have been validated by quantitative reverse
transcription polymerase chain reaction (RT-qPCR). Enrichment analyses of altered
miRNA expression were predicted using bioinformatic tools. RESULTS: Compared with
healthy controls, a total of 49, 58 and 77 miRNAs were found to be significantly
altered in TOF patients (TOF-all), TOF patients with (TOF-HF) and without
symptomatic right heart failure (TOF-noHF) (>2.0-fold change, adjusted P < 0.05),
respectively. Three miRNAs namely miR-181d-5p, miR-206 and miR-625-5p were
validated by RT-qPCR in all TOF groups. The area under the receiver operating
characteristic curve (AUC) for miR-181d-5p, miR-206 and miR-625-5p were 0.987,
0.993 and 0.769 in TOF-all and 0.990, 0.994 and 0.749 in TOF-noHF, respectively.
Moreover, expression levels of miR-625-5p, miR-1233-3p and miR-421 were lower in
TOF-HF compared to TOF-noHF (P = 0.012). CONCLUSIONS: Altered expression levels
of circulating miRNAs were found in TOF patients late after surgical repair and
are different to those seen in the right ventricular myocardium of infants with
TOF. Expression levels of miR-421, miR-1233-3p and miR-625-5p are lower in TOF
patients with symptomatic right heart failure and thus may indicate disease
progression in these patients.
PMID- 28693531
TI - Warm-needling acupuncture and medicinal cake-separated moxibustion for
hyperlipidemia: study protocol for a randomized controlled trial.
AB - BACKGROUND: Acupuncture and moxibustion has been widely applied to hyperlipidemia
treatment in clinical practice in China, serving as an alternative treatment to
statins. Warm-needling acupuncture and medicinal cake-separated moxibustion have
been separately reported with potential therapeutic effects on hyperlipidemia
treatment in several studies but with limitations in study methodology. Combining
these two modalities may provide a more advantageous strategy in treating
hyperlipidemia. Therefore, a strict evaluation through well-designed randomized
controlled trials (RCT) is necessary to determine their efficacy and safety on
hyperlipidemia. METHODS: The study a multicenter, open-label, randomized,
stratified, active-controlled, noninferiority trial with two parallel groups.
Subjects with hyperlipidemia will be stratified into different groups by risk
levels of heart diseases. They then will be instructed to the Therapeutic
Lifestyle Change (TLC) diet. Those who have not reached the target lipid level
will be randomly assigned to the treatments of either acupuncture and moxibustion
or simvastatin with a 1:1 allocation. One hundred and thirty subjects are aimed
to be recruited. The duration of intervention for this study will be 12 weeks,
followed by another 4 weeks for post-treatment assessment. The primary outcome is
percentage change from baseline to the end of the study in low-density
lipoprotein cholesterol (LDL-C). Other indicators in lipid change, safety and
adherence will also be assessed secondarily. The repeated measures, linear mixed
effects model will be applied to the analysis. DISCUSSION: Acupuncture and
moxibustion could be a potentially effective treatment alternative for
hyperlipidemia. A study with careful design is developed to evaluate the efficacy
and safety of combined acupuncture and moxibustion, by integrating the
traditional Chinese Medicine (TCM) regimens with the standardized Western
medicine appraisal approach. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02269046
. Registered on 26 September 2014.
PMID- 28693532
TI - Joint quantitative measurement of hTERT mRNA in both peripheral blood and
circulating tumor cells of patients with nasopharyngeal carcinoma and its
clinical significance.
AB - BACKGROUND: The study was aimed to quantitatively detect mRNA levels of the
catalytic subunit of telomerase (hTERT) in both peripheral blood and circulating
tumor cells (CTCs) of patients with nasopharyngeal carcinoma (NPC) and explore
its significance in early diagnosis and treatment of NPC. METHODS: hTERT mRNA
levels in peripheral blood and CTCs of 33 NPC patients before and after treatment
with intensity-modulated radiation therapy (IMRT) or/and chemotherapy and 24
healthy controls were measured using real-time quantitative PCR (qPCR) and their
correlations to clinic pathological factors of NPC were analyzed. RESULTS:
Peripheral hTERT mRNA content was 10.75 +/- 4.29 in NPC patients and 0.95 +/-
0.37 in control subjects (P < 0.05), and had a significant correlation with
patients' clinical stage, T stage, and N stage (P < 0.05). Treatment of NPC
patients at stages I and II with simple IMRT significantly reduced hTERT mRNA
level from 5.60 +/- 2.33 to 3.43 +/- 1.42 (P < 0.05) and treatment of patients at
advanced stage (III and IV) with induction chemotherapy followed by IMRT
significantly reduced hTERT mRNA levels from 12.68 +/- 3.08 to 10.68 +/- 2.48 to
3.13 +/- 1.69 (P < 0.05), respectively. In addition, the study also showed that
hTERT mRNA content in CTCs of NPC patients was 10.65 +/- 4.28, evidently higher
than that of 1.09 +/- 0.40 in control subjects (P < 0.05) and hTERT mRNA level in
CTCs of NPC patients was obviously correlated to patients' clinical stage, T
stage and N stage (P < 0.05). After treatment, hTERT mRNA level in CTCs of NPC
patients lowered from 10.65 +/- 4.28 to 5.59 +/- 2.32 (P < 0.05). The correlation
analysis found that hTERT mRNA level in peripheral blood and CTCs of NPC patients
were highly correlated with a correlation coefficient of 0.981. CONCLUSIONS:
hTERT mRNA levels in peripheral blood and CTCs of NPC patients were significantly
enhanced compared to that in healthy controls and highly correlated. Changes in
hTERT mRNA level was closely correlated to patients' clinical stage and T stage.
Radiochemotherapy could effectively reduce hTERT mRNA level in peripheral blood
and CTCs. Thus, it is possible using the joint detection of hTERT mRNA level in
peripheral blood and CTCs as a new biomarker for early diagnosis, treatment
efficacy and prognosis of NPC.
PMID- 28693533
TI - Classification complexity in myoelectric pattern recognition.
AB - BACKGROUND: Limb prosthetics, exoskeletons, and neurorehabilitation devices can
be intuitively controlled using myoelectric pattern recognition (MPR) to decode
the subject's intended movement. In conventional MPR, descriptive
electromyography (EMG) features representing the intended movement are fed into a
classification algorithm. The separability of the different movements in the
feature space significantly affects the classification complexity. Classification
complexity estimating algorithms (CCEAs) were studied in this work in order to
improve feature selection, predict MPR performance, and inform on faulty data
acquisition. METHODS: CCEAs such as nearest neighbor separability (NNS), purity,
repeatability index (RI), and separability index (SI) were evaluated based on
their correlation with classification accuracy, as well as on their suitability
to produce highly performing EMG feature sets. SI was evaluated using Mahalanobis
distance, Bhattacharyya distance, Hellinger distance, Kullback-Leibler
divergence, and a modified version of Mahalanobis distance. Three commonly used
classifiers in MPR were used to compute classification accuracy (linear
discriminant analysis (LDA), multi-layer perceptron (MLP), and support vector
machine (SVM)). The algorithms and analytic graphical user interfaces produced in
this work are freely available in BioPatRec. RESULTS: NNS and SI were found to be
highly correlated with classification accuracy (correlations up to 0.98 for both
algorithms) and capable of yielding highly descriptive feature sets.
Additionally, the experiments revealed how the level of correlation between the
inputs of the classifiers influences classification accuracy, and emphasizes the
classifiers' sensitivity to such redundancy. CONCLUSIONS: This study deepens the
understanding of the classification complexity in prediction of motor volition
based on myoelectric information. It also provides researchers with tools to
analyze myoelectric recordings in order to improve classification performance.
PMID- 28693534
TI - Polycystic ovary syndrome induced by exposure to testosterone propionate and
effects of sympathectomy on the persistence of the syndrome.
PMID- 28693535
TI - Alfredson versus Silbernagel exercise therapy in chronic midportion Achilles
tendinopathy: study protocol for a randomized controlled trial.
AB - BACKGROUND: Midportion Achilles tendinopathy (AT) is a common overuse injury,
usually requiring several months of rehabilitation. Exercise therapy of the ankle
plantar flexors (i.e. tendon loading) is considered crucial during conservative
rehabilitation. Alfredson's isolated eccentric and Silbernagel's combined
concentric-eccentric exercise programs have both shown beneficial results, but it
is unknown whether any of these programs is superior for use in clinical
practice. Therefore, the primary objective of this study is to compare the
effectiveness of both programs on clinical symptoms. Secondary objectives are to
compare the effectiveness of both programs on quality of life and functional
outcome measures, to investigate the prognostic value of baseline
characteristics, to investigate differences in cost-effectiveness.
METHODS/DESIGN: Eighty-six recreational athletes (21-60 years of age) with
unilateral chronic midportion AT (i.e. >= 3 months) will be included in this
multicenter assessor blinded randomized controlled trial. They will be randomly
allocated to either a group performing the Alfredson isolated eccentric training
program (n = 43), or a group performing the Silbernagel combined concentric
eccentric program (n = 43). In the Alfredson group, participants will perform
eccentric heel-drops on their injured side, twice daily for 12 weeks, whereas in
the Silbernagel group, participants perform various concentric-eccentric heel
raise exercises, once daily for 12 weeks. Primary outcome measure will be the
Victorian Institute of Sport Assessment - Achilles (VISA-A) questionnaire.
Secondary outcomes will be a visual analogue scale (VAS) for pain during daily
activities and sports, duration of morning stiffness, global perceived effect,
the 12-item Short Form Health Survey and the Euroqol instrument, and functional
performance measured with the heel-raise test and the countermovement jump.
Additionally, alongside the RCT, a cost-effectiveness analysis will be performed.
Assessments will be performed at baseline and after 12, 26, and 52 weeks.
DISCUSSION: This study is the first to directly compare the Alfredson and the
Silbernagel exercise program in a randomized trial. The results can further
enlarge the evidence base for choosing the most appropriate exercise program for
patients with midportion AT. TRIAL REGISTRATION: Dutch Trial register: NTR5638 .
Date of registration: 7 January 2016.
PMID- 28693536
TI - Hypothermia induced alteration of repolarization - impact on acute and long-term
outcome: a prospective cohort study.
AB - BACKGROUND: The effects of target temperature management (TTM) on the heart
aren't thoroughly studied yet. Several studies showed the prolongation of various
ECG parameters including Tpeak-Tend-time under TTM. Our study's goal is to
evaluate the acute and long-term outcome of these prolongations. METHODS: In this
study we included patients with successful resuscitation after cardiac arrest who
were admitted to the Charite Virchow Klinikum Berlin or the Heart and Vascular
Centre of the Ruhr University Bochum between February 2006 and July 2013 (Berlin)
or May 2014 to November 2015 (Bochum). For analysis, one ECG during TTM was
recorded after reaching the target temperature (33-34 degrees C) or in the first
6 h of TTM. If possible, another ECG was taken after TTM. The patients were being
followed until February 2016. Primary endpoint was ventricular arrhythmia during
TTM, secondary endpoints were death and hospitalization due to cardiovascular
diseases during follow-up. RESULTS: One hundred fifty-eight patients were
successfully resuscitated in the study period of which 95 patients had usable
data (e.g. ECGs without artifacts). During TTM significant changes for different
parameters of ventricular de- and repolarization were noted: QRS (103.2 +/- 23.7
vs. 95.3 +/- 18.1; p = 0.003),QT (405.8 +/- 76.4 vs. 373.8 +/- 75.0; p = 0.01),
QTc (474.9 +/- 59.7 vs. 431.0 +/- 56.8; p < 0.001), JT (302.8 +/- 69.4 vs. 278.5
+/- 75.2; p = 0.043), JTc (354.3 +/- 60.2 vs. 318.7 +/- 59.1; p = 0.001). 13.7%
of the patients had ventricular arrhythmias during TTM, however these patients
showed no difference regarding their ECG parameters in comparison to those were
no ventricular arrhythmias occurred. We were able to follow 69 Patients over an
average period of 35 +/- 31 months. The 14 (21.5%) patients who died during the
follow-up had significant prolongations of the TpTe-time in the ECGs without TTM
(103.9 +/- 47.2 vs. 75.8 +/- 28.6; p = 0.023). CONCLUSION: Our results show a
significant prolongation of ventricular repolarization during TH. However, there
was no significant difference between the ECG parameters of those who developed a
ventricular arrhythmia and those who did not. The temporary prolongation of the
repolarization during TTM seems to be less important for the prognosis of the
patient. Whereas the prolongation of the repolarization in the basal ECG is
associated with a higher mortality in our study.
PMID- 28693537
TI - Erratum to: Intratumoral and peritumoral radiomics for the pretreatment
prediction of pathological complete response to neoadjuvant chemotherapy based on
breast DCE-MRI.
PMID- 28693538
TI - Patient benefit of dog-assisted interventions in health care: a systematic
review.
AB - BACKGROUND: Dogs are the most common companion animal, and therefore not
surprisingly a popular choice for animal-assisted interventions. Dog-assisted
interventions are increasingly used in healthcare. The aim of the review was to
conduct a systematic literature review of quantitative studies on dog-assisted
interventions in healthcare, with the intention of assessing the effects and cost
effectiveness of the interventions for different categories of patients. METHODS:
A systematic review of the scientific literature reporting results of studies in
healthcare, nursing home or home care settings, was conducted. The inclusion
criteria applied for this review were: quantitative studies, inclusion of at
least 20 study subjects, existence of a control and performed in healthcare
settings including nursing homes and home care. The electronic databases PubMed,
AMED, CINAHL and Scopus were searched from their inception date through January
2017, for published articles from peer-reviewed journals with full text in
English. RESULTS: Eighteen studies that fulfilled the inclusion criteria, and
were judged to be of at least moderate quality, were included in the analysis.
Three of them showed no effect. Fifteen showed at least one significant positive
effect but in most studied outcome measures there was no significant treatment
effect. Dog-assisted therapy had the greatest potential in treatment of
psychiatric disorders among both young and adult patients. Dog-assisted
activities had some positive effects on health, wellbeing, depression and quality
of life for patients with severe cognitive disorders. Dog-assisted support had
positive effects on stress and mood. CONCLUSIONS: The overall assessment of the
included studies indicates minor to moderate effects of dog-assisted therapy in
psychiatric conditions, as well as for dog-assisted activities in cognitive
disorders and for dog-assisted support in different types of medical
interventions. However, the majority of studied outcome measures showed no
significant effect.
PMID- 28693539
TI - Genomic prediction in contrast to a genome-wide association study in explaining
heritable variation of complex growth traits in breeding populations of
Eucalyptus.
AB - BACKGROUND: The advent of high-throughput genotyping technologies coupled to
genomic prediction methods established a new paradigm to integrate genomics and
breeding. We carried out whole-genome prediction and contrasted it to a genome
wide association study (GWAS) for growth traits in breeding populations of
Eucalyptus benthamii (n =505) and Eucalyptus pellita (n =732). Both species are
of increasing commercial interest for the development of germplasm adapted to
environmental stresses. RESULTS: Predictive ability reached 0.16 in E. benthamii
and 0.44 in E. pellita for diameter growth. Predictive abilities using either
Genomic BLUP or different Bayesian methods were similar, suggesting that growth
adequately fits the infinitesimal model. Genomic prediction models using ~5000
10,000 SNPs provided predictive abilities equivalent to using all 13,787 and
19,506 SNPs genotyped in the E. benthamii and E. pellita populations,
respectively. No difference was detected in predictive ability when different
sets of SNPs were utilized, based on position (equidistantly genome-wide, inside
genes, linkage disequilibrium pruned or on single chromosomes), as long as the
total number of SNPs used was above ~5000. Predictive abilities obtained by
removing relatedness between training and validation sets fell near zero for E.
benthamii and were halved for E. pellita. These results corroborate the current
view that relatedness is the main driver of genomic prediction, although some
short-range historical linkage disequilibrium (LD) was likely captured for E.
pellita. A GWAS identified only one significant association for volume growth in
E. pellita, illustrating the fact that while genome-wide regression is able to
account for large proportions of the heritability, very little or none of it is
captured into significant associations using GWAS in breeding populations of the
size evaluated in this study. CONCLUSIONS: This study provides further
experimental data supporting positive prospects of using genome-wide data to
capture large proportions of trait heritability and predict growth traits in
trees with accuracies equal or better than those attainable by phenotypic
selection. Additionally, our results document the superiority of the whole-genome
regression approach in accounting for large proportions of the heritability of
complex traits such as growth in contrast to the limited value of the local GWAS
approach toward breeding applications in forest trees.
PMID- 28693540
TI - Gallie technique versus atlantoaxial screw-rod constructs in the treatment of
atlantoaxial sagittal instability: a retrospective study of 49 patients.
AB - BACKGROUND: The objectives of this study are to investigate the clinical curative
effect of Gallie technique and atlantoaxial screw-rod constructs (SRC) on
atlantoaxial sagittal instability and determine the indication of Gallie
technique. METHODS: Data of 49 patients with atlantoaxial sagittal instability
from February 2008 to May 2015 were analyzed retrospectively. The visual analog
scale (VAS) score and the neck disability index (NDI) were used to evaluate the
curative effect. Postoperative radiological outcomes were used to evaluate the
stability of atlantoaxial joint and bone fusion. Perioperative parameters such as
blood loss, operation time, radiographic exposure times, and hospital expense
were also recorded and analyzed. RESULTS: Forty-nine patients (36 men and 13
women) were included in this study. The mean age was 41.4 +/- 8.9 (range from 19
to 64). All patients were followed up for 24-67 months. Among these patients, 25
of these patients underwent Gallie surgery and 24 underwent SRC surgery. The pain
in the occipitocervical area of all the patients has been relieved. NDI scores
and VAS scores were lower in Gallie group than in SRC group in early
postoperative period. The proportion of the patients who achieved good bone
fusion within 3 months after operation was 88.0% (22/25) in the Gallie group and
100% (24/24) in the SRC group. The Gallie group is lower than the SRC group in
blood loss, operation time, radiographic exposure times, and hospital expense.
Statistical difference was observed between the two groups. CONCLUSIONS: For
patients with atlantoaxial instability who has (1) the atlantodental interval
(ADI) which is bigger than 5 mm on lateral flexion-extension X-ray, or Anderson
D'Alonzo type II odontoid fracture, (2) no asymmetry between odontoid process and
lateral mass on open-mouth anterior-posterior X-ray, and (3) no dislocation of
lateral mass joint on the CT 3D reconstruction, Gallie technique can be chosen as
a safe and effective method if atlantoaxial reduction can be achieved
preoperatively. Compared with SRC, Gallie technique can relieve the pain in the
occipitocervical area earlier and it can shorten operation time and reduce
intraoperative bleeding, radiographic exposure times, and hospital expense
effectively. However, for patients with irreducible atlantoaxial dislocation, the
Gallie technique should be used with caution.
PMID- 28693541
TI - Is HPA axis reactivity in childhood gender-specific? A systematic review.
AB - BACKGROUND: In adults, hypothalamus-pituitary-adrenal (HPA) axis activity shows
sexual dimorphism, and this is thought to be a mechanism underlying sex-specific
disease incidence. Evidence is scarce on whether these sex differences are also
present in childhood. In a meta-analysis, we recently found that basal (non
stimulated) cortisol in saliva and free cortisol in 24-h urine follow sex
specific patterns. We explored whether these findings could be extended with sex
differences in HPA axis reactivity. METHODS: From inception to January 2016,
PubMed and EMBASE.com were searched for studies that assessed HPA axis reactivity
in healthy girls and boys aged <=18 years. Articles were systematically assessed
and reported in the categories: (1) diurnal rhythm, (2) cortisol awakening
response (CAR), (3) protocolled social stress tests similar or equal to the Trier
Social Stress Test for children (TSST-C), (4) pharmacological (ACTH and CRH)
stress tests, and (5) miscellaneous stress tests. RESULTS: Two independent
assessors selected 109 out of 6158 records for full-text screening, of which 81
studies (with a total of 14,591 subjects) were included. Studies showed that
girls had a tendency towards a more variable diurnal rhythm (12 out of 29
studies), a higher CAR (8 out of 18 studies), and a stronger cortisol response to
social stress tests (9 out of 21 studies). We found no evidence for sex
differences in cortisol response after a pharmacological challenge or to
miscellaneous stress tests. DISCUSSION: Sex differences in HPA axis reactivity
appear to be present in childhood, although evidence is not unequivocal. For a
better evaluation of sex differences in HPA axis reactivity, standardization of
protocols and reports of stress tests is warranted.
PMID- 28693542
TI - Overview of methodologies for T-cell receptor repertoire analysis.
AB - BACKGROUND: The T-cell receptor (TCR), located on the surface of T cells, is
responsible for the recognition of the antigen-major histocompatibility complex,
leading to the initiation of an inflammatory response. Analysing the TCR
repertoire may help to gain a better understanding of the immune system features
and of the aetiology and progression of diseases, in particular those with
unknown antigenic triggers. The extreme diversity of the TCR repertoire
represents a major analytical challenge; this has led to the development of
specialized methods which aim to characterize the TCR repertoire in-depth.
Currently, next generation sequencing based technologies are most widely employed
for the high-throughput analysis of the immune cell repertoire. RESULTS: Here, we
report on the latest methodological advancements in the field by describing and
comparing the available tools; from the choice of the starting material and
library preparation method, to the sequencing technologies and data analysis.
Finally, we provide a practical example and our own experience by reporting some
exemplary results from a small internal benchmark study, where current approaches
from the literature and the market are employed and compared. CONCLUSIONS:
Several valid methods for clonotype identification and TCR repertoire analysis
exist, however, a gold standard method for the field has not yet been identified.
Depending on the purpose of the scientific study, some approaches may be more
suitable than others. Finally, due to possible method specific biases, scientists
must be careful when comparing results obtained using different methods.
PMID- 28693543
TI - Finite Element Analysis of porously punched prosthetic short stem virtually
designed for simulative uncemented Hip Arthroplasty.
AB - BACKGROUND: There is no universal hip implant suitably fills all femoral types,
whether prostheses of porous short-stem suitable for Hip Arthroplasty is to be
measured scientifically. METHODS: Ten specimens of femurs scanned by CT were
input onto Mimics to rebuild 3D models; their *stl format dataset were imported
into Geomagic-Studio for simulative osteotomy; the generated *.igs dataset were
interacted by UG to fit solid models; the prosthesis were obtained by the same
way from patients, and bored by punching bears designed by Pro-E virtually;
cements between femora and prosthesis were extracted by deleting prosthesis; in
HyperMesh, all compartments were assembled onto four artificial joint style as:
(a) cemented long-stem prosthesis; (b) porous long-stem prosthesis; (c) cemented
short-stem prosthesis; (d) porous short-stem prosthesis. Then, these numerical
models of Finite Element Analysis were exported to AnSys for numerical solution.
RESULTS: Observed whatever from femur or prosthesis or combinational femora
prostheses, "Kruskal-Wallis" value p > 0.05 demonstrates that displacement of (d)
~ (a) ~ (b) ~ (c) shows nothing different significantly by comparison with 600 N
load. If stresses are tested upon prosthesis, (d) ~ (a) ~ (b) ~ (c) is also
displayed; if upon femora, (d) ~ (a) ~ (b) < (c) is suggested; if upon integral
joint, (d) ~ (a) < (b) < (c) is presented. CONCLUSIONS: Mechanically, these four
sorts of artificial joint replacement are stabilized in quantity. Cemented short
stem prostheses present the biggest stress, while porous short-stem & cemented
long-stem designs are equivalently better than porous long-stem prostheses and
alternatives for femoral-head replacement. The preferred design of those two
depends on clinical conditions. The cemented long-stem is favorable for inactive
elders with osteoporosis, and porously punched cementless short-stem design is
suitable for patients with osteoporosis, while the porously punched cementless
short-stem is favorable for those with a cement allergy. Clinically, the strength
of this study is to enable preoperative strategy to provide acute correction and
decrease procedure time.
PMID- 28693544
TI - McMaster Optimal Aging Portal: an evidence-based database for geriatrics-focused
health professionals.
AB - OBJECTIVE: The objective of this work was to provide easy access to reliable
health information based on good quality research that will help health care
professionals to learn what works best for seniors to stay as healthy as
possible, manage health conditions and build supportive health systems. This will
help meet the demands of our aging population that clinicians provide high
quality care for older adults, that public health professionals deliver disease
prevention and health promotion strategies across the life span, and that
policymakers address the economic and social need to create a robust health
system and a healthy society for all ages. RESULTS: The McMaster Optimal Aging
Portal's (Portal) professional bibliographic database contains high quality
scientific evidence about optimal aging specifically targeted to clinicians,
public health professionals and policymakers. The database content comes from
three information services: McMaster Premium LiteratUre Service (MacPLUSTM),
Health EvidenceTM and Health Systems Evidence. The Portal is continually updated,
freely accessible online, easily searchable, and provides email-based alerts when
new records are added. The database is being continually assessed for value,
usability and use. A number of improvements are planned, including French
language translation of content, increased linkages between related records
within the Portal database, and inclusion of additional types of content. While
this article focuses on the professional database, the Portal also houses
resources for patients, caregivers and the general public, which may also be of
interest to geriatric practitioners and researchers.
PMID- 28693545
TI - Competence profiles in undergraduate dental education: a comparison between
theory and reality.
AB - BACKGROUND: Competence profiles are purposed to provide a blueprint in support to
develop and/or benchmark the learning outcomes of undergraduate dental curricula.
This study aims to investigate whether a competence profile as proposed by
academic- and clinical experts is able to represent the real clinical reality.
METHODS: A questionnaire was developed including questions about gender and age,
perception about required competences, and educational organisation and was
distributed among Flemish dentists via email and on paper during a symposium. The
data was analysed using descriptive statistics, Chi-square and non-parametric
Mann-Whitney U-tests. RESULTS: A total of 312 questionnaires were completed
(=6.5% of dentist population, with similar gender and age characteristics). All
competences in the European competence profile were rated between 7.2 and 9.4 on
a 10-point scale. In dentists under 50 years, females rated the importance of
identifying/managing anxiety and abnormal patient behaviour; and
promoting/improving oral health as significantly higher than males. In dentists
of 50 years and above, females rated 8 competences significantly higher than
males, including obtaining/recording a complete history; identifying/managing
anxiety and abnormal patient behaviour; obtaining/interpreting radiography;
identifying temporomandibular and associated disorders; identifying orthodontic
needs; awareness of own limitations/when to refer; managing dental urgencies; and
basic-life-support/defibrillation. Clinical practice management was most
frequently reported as additional competence to address in dental education.
Furthermore, the respondents suggested an undergraduate dental curriculum based
on 34% theoretical education, 26% preclinical skills training, and 40% clinical
education and 86% agreed with a duration of 5 years. Finally, the respondents
also illustrated the dynamic nature of dentistry including a reduction of amalgam
fillings, a shift from individual practice to group practices, an increased
administrative load, and more assertive patients. CONCLUSION: Findings in the
present study suggest the validation of the proposed competences for graduating
European dentists within the clinical reality of dental professionals in daily
practice. Nevertheless, the results have also demonstrated heterogeneity
regarding gender and age within the dentist population and emphasised a
continuously evolving dental profession and required competences. Hence, to
maintain high quality of dental care, a strategy should be developed in which
dental curricula are continuously benchmarked against an evolving clinical
reality.
PMID- 28693546
TI - Successful treatment of refractory complete separation of an esophagojejunal
anastomosis after laparoscopic total gastrectomy: a case report.
AB - BACKGROUND: Anastomotic leakage after total gastrectomy occurs despite
improvements in surgical techniques and patient management. Although many cases
of dehiscence can be managed non-operatively, major leakage requires a second
surgery and can potentially lead to death. Therefore, accurate and immediate
diagnosis and treatment are essential. CASE PRESENTATION: In this report, we
describe a 66-year-old Japanese man who was diagnosed with a complete separation
of an esophagojejunal anastomosis after laparoscopic total gastrectomy with oral
contrast radiography using Gastrografin(r). The severe complication was
successfully treated by re-anastomosis after two emergency drainage surgeries.
After the second surgery, the esophageal end formed a fistula with the jejunum,
but balloon dilation failed to open the fistula. Therefore, oral ingestion and
conservative treatment were considered unsuitable, and we performed
esophagojejunal re-anastomosis 7 months after the first surgery. At a follow-up
examination 2 years after re-anastomosis, the patient weighed 47 kg, and his
ingestion had recovered to 80% of that before surgery. CONCLUSIONS: Complete
separation of an esophagojejunal anastomosis is a rare but severe complication of
total gastrectomy. Therefore, we consider that once separation is diagnosed,
aggressive and urgent re-operation and effective drainage are useful. Moreover,
it is necessary to take great care to minimize the operative morbidity associated
with esophagojejunal anastomosis.
PMID- 28693547
TI - Longitudinal associations between built environment characteristics and changes
in active commuting.
AB - BACKGROUND: Few studies have assessed the predictors of changes in commuting.
This study investigated the associations between physical environmental
characteristics and changes in active commuting. METHODS: Adults from the
population-based European Prospective Investigation into Cancer (EPIC)-Norfolk
cohort self-reported commuting patterns in 2000 and 2007. Active commuters were
defined as those who reported 'always' or 'usually' walking or cycling to work.
Environmental attributes around the home and route were assessed using
Geographical Information Systems. Associations between potential environmental
predictors and uptake and maintenance of active commuting were modelled using
logistic regression, adjusting for age, sex and BMI. RESULTS: Of the 2757
participants (62% female, median baseline age: 52, IQR: 50-56 years), most were
passive commuters at baseline (76%, n = 2099) and did not change their usual
commute mode over 7 years (82%, n = 2277). In multivariable regression models,
participants living further from work were less likely to take up active
commuting and those living in neighbourhoods with more streetlights were more
likely to take up active commuting (both p < 0.05). Findings for maintenance were
similar: participants living further from work (over 10 km, OR: 0.06; 95% CI:
0.25 to 0.13) and had a main or secondary road on route were more likely to
maintain their active commuting (OR: 0.52; 95% CI: 0.28 to 0.98). Those living in
neighbourhoods with greater density of employment locations were more likely to
maintain their active commuting. CONCLUSIONS: Co-locating residential and
employment centres as well as redesigning urban areas to improve safety for
pedestrians and cyclists may encourage active commuting. Future evaluative
studies should seek to assess the effects of redesigning the built environment on
active commuting and physical activity.
PMID- 28693548
TI - Using a linked database for epidemiology across the primary and secondary care
divide: acute kidney injury.
AB - BACKGROUND: NHS England has mandated the use in hospital laboratories of an
automated early warning algorithm to create a consistent method for the detection
of acute kidney injury (AKI). It generates an 'alert' based on changes in serum
creatinine level to notify attending clinicians of a possible incident case of
the condition, and to provide an assessment of its severity. We aimed to explore
the feasibility of secondary data analysis to reproduce the algorithm outside of
the hospital laboratory, and to describe the epidemiology of AKI across primary
and secondary care within a region. METHODS: Using the Hampshire Health Record
Analytical database, a patient-anonymised database linking primary care,
secondary care and hospital laboratory data, we applied the algorithm to one year
(1st January-31st December 2014) of retrospective longitudinal data. We developed
database queries to modularise the collection of data from various sectors of the
local health system, recreate the functions of the algorithm and undertake data
cleaning. RESULTS: Of a regional population of 642,337 patients, 176,113 (27.4%)
had two or more serum creatinine test results available, with testing more common
amongst older age groups. We identified 5361 (or 0.8%) with incident AKI
indicated by the algorithm, generating a total of 13,845 individual AKI alerts. A
cross-sectional assessment of each patient's first alert found that more than two
thirds of cases originated in the community, of which nearly half did not lead to
a hospital admission. CONCLUSION: It is possible to reproduce the algorithm using
linked primary care, secondary care and hospital laboratory data, although data
completeness, data quality and technical issues must be overcome. Linked data is
essential to follow the significant proportion of people with AKI who transition
from primary to secondary care, and can be used to assess clinical outcomes and
the impact of interventions across the health system. This study emphasises that
the development of data systems bridging across different sectors of the health
and social care system can provide benefits for researchers, clinicians,
healthcare providers and commissioners.
PMID- 28693550
TI - Evidence of indirect symbiont conferred protection against the predatory lady
beetle Harmonia axyridis in the pea aphid.
AB - BACKGROUND: Defensive symbionts can provide significant fitness advantages to
their hosts. Facultative symbionts can protect several species of aphid from
fungal pathogens, heat shock, and parasitism by parasitoid wasps. Previous work
found that two of these facultative symbionts can also indirectly protect pea
aphids from predation by the lady beetle Hippocampus convergens. When aphids
reproduce asexually, there is extremely high relatedness among aphid clone-mates
and often very limited dispersal. Under these conditions, symbionts may
indirectly protect aphid clone-mates from predation by negatively affecting the
survival of a predator after the consumption of aphids harboring the same
vertically transmitted facultative symbionts. In this study, we wanted to
determine whether this indirect protection extended to another lady beetle
species, Harmonia axyridis. RESULTS: We fed Ha. axyridis larvae aphids from one
of four aphid sub-clonal symbiont lines which all originated from the same
naturally symbiont free clonal aphid lineage. Three of the sub-clonal lines
harbor different facultative symbionts that were introduced to the lines via
microinjection. Therefore these sub-clonal lineages vary primarily in their
symbiont composition, not their genetic background. We found that aphid
facultative symbionts affected larval survival as well as pupal survival in their
predator Ha. axyridis. Additionally, Ha. axyridis larvae fed aphids with the
Regiella symbiont had significantly longer larval developmental times than beetle
larvae fed other aphids, and females fed aphids with the Regiella symbiont as
larvae weighed less as adults. These fitness effects were different from those
previously found in another aphid predator Hi. convergens suggesting that the
fitness effects may not be the same in different aphid predators. CONCLUSIONS:
Overall, our findings suggest that some aphid symbionts may indirectly benefit
their clonal aphid hosts by negatively impacting the development and survival of
a lady beetle aphid predator Ha. axyridis. By directly affecting the survival of
predatory lady beetles, aphid facultative symbionts may increase the survival of
their clone-mates that are clustered nearby and have significant impacts across
multiple trophic levels. We have now found evidence for multiple aphid
facultative symbionts negatively impacting the survival of a second species of
aphid predatory lady beetle. These same symbionts also protect their hosts from
parasitism and fungal infections, though these fitness effects seem to depend on
the aphid species, predator or parasitoid species, and symbiont type. This work
further demonstrates that beneficial mutualisms depend upon complex interactions
between a variety of players and should be studied in multiple ecologically
relevant contexts.
PMID- 28693551
TI - Volunteering and health benefits in general adults: cumulative effects and forms.
AB - BACKGROUND: Although the health benefits of volunteering have been well
documented, no research has examined its cumulative effects according to other
oriented and self-oriented volunteering on multiple health outcomes in the
general adult public. This study examined other-oriented and self-oriented
volunteering in cumulative contribution to health outcomes (mental and physical
health, life satisfaction, social well-being and depression). METHODS: Data were
drawn from the Survey of Texas Adults 2004, which contains a statewide population
based sample of adults (n = 1504). Multivariate linear regression and Wald test
of parameters equivalence constraint were used to test the relationships.
RESULTS: Both forms of volunteering were significantly related to better health
outcomes (odds ratios = 3.66% to 11.11%), except the effect of self-oriented
volunteering on depression. Other-oriented volunteering was found to have better
health benefits than did self-volunteering. CONCLUSION: Volunteering should be
promoted by public health, education and policy practitioners as a kind of
healthy lifestyle, especially for the social subgroups of elders, ethnic
minorities, those with little education, single people, and unemployed people,
who generally have poorer health and less participation in volunteering.
PMID- 28693552
TI - Chloroquine efficacy for Plasmodium vivax in Myanmar in populations with high
genetic diversity and moderate parasite gene flow.
AB - BACKGROUND: Plasmodium vivax malaria remains a major public health burden in
Myanmar. Resistance to chloroquine (CQ), the first-line treatment for P. vivax,
has been reported in the country and has potential to undermine local control
efforts. METHODS: Patients over 6 years of age with uncomplicated P. vivax mono
infection were enrolled into clinical efficacy studies in Myawaddy in 2014 and
Kawthoung in 2012. Study participants received a standard dose of CQ (25 mg/kg
over 3 days) followed by weekly review until day 28. Pvmdr1 copy number (CN) and
microsatellite diversity were assessed on samples from the patients enrolled in
the clinical study and additional cross-sectional surveys undertaken in Myawaddy
and Shwegyin in 2012. RESULTS: A total of 85 patients were enrolled in the CQ
clinical studies, 25 in Myawaddy and 60 in Kawthoung. One patient in Myawaddy
(1.2%) had an early treatment failure and two patients (2.3%) in Kawthoung
presented with late treatment failures on day 28. The day 28 efficacy was 92.0%
(95% CI 71.6-97.9) in Myawaddy and 98.3% (95% CI 88.7-99.8) in Kawthoung. By day
2, 92.2% (23/25) in Myawaddy and 85.0% (51/60) in Kawthoung were aparasitaemic.
Genotyping and pvmdr1 CN assessment was undertaken on 43, 52 and 46 clinical
isolates from Myawaddy, Kawthoung and Shwegyin respectively. Pvmdr1 amplification
was observed in 3.2% (1/31) of isolates in Myawaddy, 0% (0/49) in Kawthoung and
2.5% (1/40) in Shwegyin. Diversity was high in all sites (H E 0.855-0.876), with
low inter-population differentiation (F ST 0.016-0.026, P < 0.05). CONCLUSIONS:
Treatment failures after chloroquine were observed following chloroquine
monotherapy, with pvmdr1 amplification present in both Myawaddy and Shwegyin. The
results emphasize the importance of ongoing P. vivax drug resistance surveillance
in Myanmar, particularly given the potential connectivity between parasite
population at different sites.
PMID- 28693553
TI - Interaction between saliva's adenosine and tick parasitism: effects on feeding
and reproduction.
AB - BACKGROUND: It has recently been demonstrated that saliva from Rhipicephalus
sanguineus ticks contains adenosine (ADO) and prostaglandin E2 (PGE2), two non
protein molecules that have significant immunomodulatory properties. These
molecules can inhibit cytokine production by dendritic cells (DCs), while also
reducing the expression of CD40 in these cells. However, more studies are needed
for a better understanding of their participation in the feeding of ticks in
vivo. This work, therefore, evaluated the importance of ADO during tick
infestations. Mice were infested with adult ticks (3 couples/mouse), and their
skin was collected at the tick-infested site (3rd and 7th day), and mRNA for
receptors of ADO was quantified by real-time PCR. RESULTS: Tick infestation
increased by four and two times the expression of the A2b and A3v1 receptors on
day 3, respectively, while expression of other ADO receptors was unaltered. In
addition, we treated mice (n = 10/group) daily with 8-(p
Sulfophenyl)theophylline, 8-pSPT, 20 mg/kg, i.p.), a non-selective antagonist of
ADO receptors, and evaluated the performance of ticks during infestations. Female
ticks fed on 8-pSPT-treated mice presented a reduction in their engorgement,
weight and hatching rates of egg masses, and survival times of larvae compared to
the same parameters presented by ticks in the control group. To investigate if
these 8-pSPT-treated mice presented altered immune responses, we performed three
tick infestations and collected their lymph node cells to determine the
percentages and activation state of DCs and cytokine production by lymphocytes by
flow cytometry (Cytometric Bead Array technique, CBA). Our data showed that 8
pSPT-treated mice presented an increase in the percentage of DCs as well as of
their stimulatory and co-stimulatory molecules (CD40, CD80 and MHCII). Regarding
production of T cell cytokines, we observed a significant increase in the levels
of IL-2 and a significant decrease in IL-10, IL-17, TNF-alpha and IFN-gamma
cytokines. CONCLUSIONS: These results suggest that ADO produced by ticks helps
them feed and reproduce and that this effect may be due to modulation of host DCs
and T cells.
PMID- 28693554
TI - Patient driven care in the management of prostate cancer: analysis of the United
States military healthcare system.
AB - BACKGROUND: Patient preferences are assumed to impact healthcare resource
utilization, especially treatment options. There is limited data exploring this
phenomenon. We sought to identify factors associated with patients transferring
care for prostatectomy, from military to civilian facilities, and the receipt of
minimally invasive radical prostatectomy (MIRP). METHODS: Retrospective review of
2006-2010 TRICARE data identified men diagnosed with prostate cancer (ICD-9 185)
receiving open radical prostatectomy (ORP; ICD-9: 60.5) or MIRP (ICD-9 60.5 +
54.21/17.42). Patients diagnosed at military facilities but underwent surgery at
civilian facilities were defined as "transferring care". Logistic regression
models identified predictors of transferring care for patients diagnosed at
military facilities. A secondary analysis identified the predictors of MIRP
receipt at civilian facilities. RESULTS: Of 1420 patients, 247 (17.4%)
transferred care. These patients were more likely to undergo MIRP (OR = 7.83, p <
0.01), and get diagnosed at low-volume military facilities (OR = 6.10, p < 0.01).
Our secondary analysis demonstrated that transferring care was strongly
associated with undergoing MIRP (OR = 1.51, p = 0.04). CONCLUSIONS: Patient
preferences induced a demand for greater utilization of MIRP and civilian
facilities. Further work exploring factors driving these preferences and
interventions tailoring them, based on evidence and cost considerations, is
required.
PMID- 28693555
TI - Delay discounting differences in brain activation, connectivity, and structure in
individuals with addiction: a systematic review protocol.
AB - BACKGROUND: Delayed reward discounting (DRD), the degree to which future rewards
are discounted relative to immediate rewards, is used as an index of impulsive
decision-making and has been associated with a number of problematic health
behaviors. Given the robust behavioral association between DRD and addictive
behavior, there is an expanding literature investigating the differences in the
functional and structural correlates of DRD in the brain between addicted and
healthy individuals. However, there has yet to be a systematic review which
characterizes differences in regional brain activation, functional connectivity,
and structure and places them in the larger context of the DRD literature. The
objective of this systematic review is to summarize and critically appraise the
existing literature examining differences between addicted and healthy
individuals in the neural correlates of DRD using magnetic resonance imaging
(MRI) or functional magnetic resonance imaging (fMRI). METHODS: A systematic
search strategy will be implemented that uses Boolean search terms in
PubMed/MEDLINE and PsycINFO, as well as manual search methods, to identify the
studies comprehensively. This review will include studies using MRI or fMRI in
humans to directly compare brain activation, functional connectivity, or
structure in relation to DRD between addicted and healthy individuals or
continuously assess addiction severity in the context of DRD. Two independent
reviewers will determine studies that meet the inclusion criteria for this
review, extract data from included studies, and assess the quality of included
studies using the Grading of Recommendations Assessment, Development and
Evaluation framework. Then, narrative review will be used to explicate the
differences in structural and functional correlates of DRD implicated by the
literature and assess the strength of evidence for this conclusion. DISCUSSION:
This review will provide a needed critical exegesis of the MRI studies that have
been conducted investigating brain differences in addictive behavior in relation
to healthy samples in the context of DRD. This will provide clarity on the
elements of neural activation, connectivity, and structure that are most
implicated in the differences in DRD seen in addicted individuals. SYSTEMATIC
REVIEW REGISTRATION: PROSPERO CRD42017056857.
PMID- 28693556
TI - Evidence for a comprehensive approach to Aboriginal tobacco control to maintain
the decline in smoking: an overview of reviews among Indigenous peoples.
AB - BACKGROUND: Tobacco smoking is a leading cause of disease and premature mortality
among Aboriginal and Torres Strait Islander (Indigenous) Australians. While the
daily smoking prevalence among Indigenous Australians has declined significantly
from 49% in 2001, it remains about three times higher than that of non-Indigenous
Australians (39 and 14%, respectively, for age >=15 years in 2014-15). This
overview of systematic reviews aimed to synthesise evidence about reducing
tobacco consumption among Indigenous peoples using a comprehensive framework for
Indigenous tobacco control in Australia comprised of the National Tobacco
Strategy (NTS) and National Aboriginal and Torres Strait Islander Health Plan
(NATSIHP) principles and priorities. METHODS: MEDLINE, EMBASE, systematic review
and Indigenous health databases were searched (2000 to Jan 2016) for reviews
examining the effects of tobacco control interventions among Indigenous peoples.
Two reviewers independently screened reviews, extracted data, and assessed review
quality using Assessing the Methodological Quality of Systematic Reviews. Data
were synthesised narratively by framework domain. Reporting followed the PRISMA
statement. RESULTS: Twenty-one reviews of varying quality were included. There
was generally limited Indigenous-specific evidence of effective interventions for
reducing smoking; however, many reviewers recommended multifaceted interventions
which incorporate Indigenous leadership, partnership and engagement and cultural
tailoring. Under the NTS priority areas, reviewers reported evidence for brief
smoking cessation interventions and pharmacological support, mass media campaigns
(on knowledge and attitudes) and reducing affordability and regulation of tobacco
sales. Aspects of intervention implementation related to the NATSIHP domains were
less well described and evidence was limited; however, reviewers suggested that
cultural tailoring, holistic approaches and building workforce capacity were
important strategies to address barriers. There was limited evidence regarding
social media and mobile applications, for Indigenous youth, pregnant women and
prisoners, and no evidence regarding interventions to protect communities from
industry interference, the use of electronic cigarettes, interventions for people
experiencing mental illness, juvenile justice, linguistic diversity or 'pubs,
clubs and restaurants'. CONCLUSIONS: There is limited Indigenous-specific
evidence for most tobacco interventions. A 'comprehensive approach' incorporating
NTS and NATSIHP Principles and Priorities of partnership and engagement, evidence
from other settings, programme logic and responsive evaluation plans may improve
intervention acceptability, effectiveness and implementation and mitigate risks
of adapting tobacco evidence for Indigenous Australians.
PMID- 28693557
TI - Prevalence of Giardia infection in households of Giardia cases and risk factors
for household transmission.
AB - BACKGROUND: Giardia is a leading but neglected cause of infectious
gastroenteritis worldwide and is treatable. There is a substantial burden of
undetected Giardia in the UK and for every one case of Giardia reported to
national surveillance there are 14 cases in the community. We aimed to ascertain
the prevalence of, and risk factors associated with secondary household Giardia
infections to assess the burden of infection and inform control measures.
METHODS: We identified all giardiasis cases notified in nine local authorities in
Lancashire between June 2014 and June 2015, and invited their household contacts
to submit faecal specimens for Giardia testing and complete a risk factor
questionnaire. We estimated the proportion of households with additional Giardia
infection. We compared household risk factors between households with and without
additional Giardia using Fisher's exact test. We used multivariable logistic
regression to identify independent risk factors for additional Giardia
infections. RESULTS: We identified additional Giardia infections in 30% (27/91)
of included households. A total of 41 infections were found from 212 household
members, of which 37 were asymptomatic. The majority of infections were
assemblage B (57%) but there were also a high number of mixed infections (20%).
Risk factors significantly associated with additional household infections were;
having children under 5 years in the household (odds ratio 42; 95% confidence
intervals 10-178) and the presence of gastrointestinal illness in the household
before the onset of the index case (odds ratio 9; 95% confidence intervals 1.5
48). CONCLUSIONS: Our finding of a high household prevalence of asymptomatic
infection has raised the public health question of whether treatment of
asymptomatic household contacts may be justified in preventing Giardia re
infection of the index case or in preventing secondary cases and household
clusters. We recommend the communication of this risk in household contacts of
Giardia and reinforcement of standard hygiene controls.
PMID- 28693558
TI - Zinc as an adjunct treatment for reducing case fatality due to clinical severe
infection in young infants: study protocol for a randomized controlled trial.
AB - BACKGROUND: An estimated 2.7 of the 5.9 million deaths in children under 5 years
of age occur in the neonatal period. Severe infections contribute to almost a
quarter of these deaths. Mortality due to severe infections in developing country
settings is substantial despite antibiotic therapy. Effective interventions that
can be added to standard therapy for severe infections are required to reduce
case fatality. METHODS/DESIGN: This is a double-blind randomized placebo
controlled parallel group superiority trial to investigate the effect of zinc
administered orally as an adjunct to standard therapy to infants aged 3 days up
to 2 months (59 days) hospitalized with clinical severe infection, that will be
undertaken in seven hospitals in Delhi, India and Kathmandu, Nepal. In a 1:1
ratio, we will randomly assign young infants to receive 10 mg of elemental zinc
or placebo orally in addition to the standard therapy for a total of 14 days. The
primary outcomes hospital case fatality, which is death due to any cause and at
any time after enrolment while hospitalized for the illness episode, and extended
case fatality, which encompasses the period until 12 weeks after enrolment.
DISCUSSION: A previous study showed a beneficial effect of zinc in reducing the
risk of treatment failure, as well as a non-significant effect on case fatality.
This study was not powered to detect an effect on case fatality, which this
current study is. If the results are consistent with this earlier trial, we would
have provided strong evidence for recommending zinc as an adjunct to standard
therapy for clinical severe infection in young infants. TRIAL REGISTRATION:
Universal Trial Number: U1111-1187-6479, Clinical Trials Registry - India:
CTRI/2017/02/007966 : Registered on February 27, 2017.
PMID- 28693559
TI - Medical diagnosis as a linguistic game.
AB - BACKGROUND: We present a formalized medical knowledge system using a linguistic
approach combined with a semantic net. METHOD: Diseases are defined and coded by
natural linguistic terms and linked via a complex network of attributes,
categories, classes, lists and other semantic conditions. RESULTS: We have
isolated more than 4600 disease entities (termed pathosoms using a made-up word)
with more than 100.000 attributes sets (termed pathophemes using a made-up word)
and a semantic net with more than 140.000 links. All major-medical thesauri like
ICD, ICD-O and OPS are included. CONCLUSIONS: Memem7 is a linguistic approach to
medical knowledge approach. With the system, we performed a proof of concept and
we conclude from our data that our or similar approaches provides reliable and
feasible tools for physicians given a formalized history taking is available. Our
approach can be considered as both a linguistic game and a third opinion to a set
of patient's data.
PMID- 28693560
TI - Ecophysiological characterization and molecular differentiation of Culex pipiens
forms (Diptera: Culicidae) in Tunisia.
AB - BACKGROUND: The Culex pipiens complex (Diptera: Culicidae) includes the most
widespread mosquito species in the world. Members of this complex are the primary
enzootic and epidemic vectors of the West Nile virus (genus Flavivirus) in
several countries. The two recognized forms of Cx. pipiens (Linnaeus, 1758) -
pipiens and molestus - exhibit behavioral and physiological differences. Natural
populations of Cx. pipiens were investigated in several sites in Tunisia to
evaluate the ecophysiological and molecular characteristics of their forms.
RESULTS: The analysis showed the sympatric presence of Cx. pipiens forms and
hybrids in all studied sites. Of all the tested larvae of Cx. pipiens, 33.5% were
identified as pipiens, 30.8% were identified as molestus, and 35.6% were
identified as hybrids. The molestus and hybrid forms were positively correlated
with urban habitats and belowground sites while the pipiens form was positively
correlated with rural habitats and aboveground sites. Autogeny was expressed in
all types of habitats and breeding sites. By contrast with the microsatellite
CQ11, the two molecular markers, ace-2 and cytb, did not allow differentiation
between the Cx. pipiens forms. CONCLUSIONS: Our study shows the ubiquitous
distribution and the plasticity of the different forms of Cx. pipiens in a wide
range of ecological conditions. It suggests that the behavioral traits assigned
to the forms of Cx. pipiens seem to be more flexible than previously assumed. Our
analysis also proves that the microsatellite CQ11 remains an efficient tool for
distinguishing between Cx. pipiens forms.
PMID- 28693561
TI - Goats as sentinel hosts for the detection of tick-borne encephalitis risk areas
in the Canton of Valais, Switzerland.
AB - BACKGROUND: Tick-borne encephalitis (TBE) is an important tick-borne disease in
Europe. Detection of the TBE virus (TBEV) in local populations of Ixodes ricinus
ticks is the most reliable proof that a given area is at risk for TBE, but this
approach is time-consuming and expensive. A cheaper and simpler approach is to
use immunology-based methods to screen vertebrate hosts for TBEV-specific
antibodies and subsequently test the tick populations at locations with
seropositive animals. RESULTS: The purpose of the present study was to use goats
as sentinel animals to identify new risk areas for TBE in the canton of Valais in
Switzerland. A total of 4114 individual goat sera were screened for TBEV-specific
antibodies using immunological methods. According to our ELISA assay, 175 goat
sera reacted strongly with TBEV antigen, resulting in a seroprevalence rate of
4.3%. The serum neutralization test confirmed that 70 of the 173 ELISA-positive
sera had neutralizing antibodies against TBEV. Most of the 26 seropositive goat
flocks were detected in the known risk areas in the canton of Valais, with some
spread into the connecting valley of Saas and to the east of the town of Brig.
One seropositive site was 60 km to the west of the known TBEV-endemic area. At
two of the three locations where goats were seropositive, the local tick
populations also tested positive for TBEV. CONCLUSION: The combined approach of
screening vertebrate hosts for TBEV-specific antibodies followed by testing the
local tick population for TBEV allowed us to detect two new TBEV foci in the
canton of Valais. The present study showed that goats are useful sentinel animals
for the detection of new TBEV risk areas.
PMID- 28693562
TI - Activation of the alpha-globin gene expression correlates with dramatic
upregulation of nearby non-globin genes and changes in local and large-scale
chromatin spatial structure.
AB - BACKGROUND: In homeotherms, the alpha-globin gene clusters are located within
permanently open genome regions enriched in housekeeping genes. Terminal
erythroid differentiation results in dramatic upregulation of alpha-globin genes
making their expression comparable to the rRNA transcriptional output. Little is
known about the influence of the erythroid-specific alpha-globin gene
transcription outburst on adjacent, widely expressed genes and large-scale
chromatin organization. Here, we have analyzed the total transcription output,
the overall chromatin contact profile, and CTCF binding within the 2.7 Mb segment
of chicken chromosome 14 harboring the alpha-globin gene cluster in cultured
lymphoid cells and cultured erythroid cells before and after induction of
terminal erythroid differentiation. RESULTS: We found that, similarly to
mammalian genome, the chicken genomes is organized in TADs and compartments. Full
activation of the alpha-globin gene transcription in differentiated erythroid
cells is correlated with upregulation of several adjacent housekeeping genes and
the emergence of abundant intergenic transcription. An extended chromosome region
encompassing the alpha-globin cluster becomes significantly decompacted in
differentiated erythroid cells, and depleted in CTCF binding and CTCF-anchored
chromatin loops, while the sub-TAD harboring alpha-globin gene cluster and the
upstream major regulatory element (MRE) becomes highly enriched with chromatin
interactions as compared to lymphoid and proliferating erythroid cells. The alpha
globin gene domain and the neighboring loci reside within the A-like chromatin
compartment in both lymphoid and erythroid cells and become further segregated
from the upstream gene desert upon terminal erythroid differentiation.
CONCLUSIONS: Our findings demonstrate that the effects of tissue-specific
transcription activation are not restricted to the host genomic locus but affect
the overall chromatin structure and transcriptional output of the encompassing
topologically associating domain.
PMID- 28693563
TI - The efficacy of traditional acupuncture on patients with chronic neck pain: study
protocol of a randomized controlled trial.
AB - BACKGROUND: A large number of randomized trials on the use of acupuncture to
treat chronic pain have been conducted. However, there is considerable
controversy regarding the effectiveness of acupuncture. We designed a randomized
trial involving patients with chronic neck pain (CNP) to investigate whether
acupuncture is more effective than a placebo in treating CNP. METHODS/DESIGN: A
five-arm, parallel, single-blinded, randomized, sham-controlled trial was
designed. Patients with CNP of more than 3 months' duration are being recruited
from Guangdong Provincial Hospital of Chinese Medicine (China). Following
examination, 175 patients will be randomized into one of five groups (35 patients
in each group) as follows: a traditional acupuncture group (group A), a shallow
puncture group (group B), a non-acupoint acupuncture group (group C), a non
acupoint shallow-puncture group (group D) and a sham-puncture group (group E).
The interventions will last for 20 min and will be carried out twice a week for 5
weeks. The primary outcome will be evaluated by changes in the Northwick Park
Neck Pain Questionnaire (NPQ). Secondary outcomes will be measured by the pain
threshold, the Short Form McGill Pain Questionnaire-2 (SF-MPQ-2), the 36-Item
Short-Form Health Survey (SF-36) and diary entries. Analysis of the data will be
performed at baseline, at the end of the intervention and at 3 months' follow-up.
The safety of acupuncture will be evaluated at each treatment period. DISCUSSION:
The purpose of this trial is to determine whether traditional acupuncture is more
effective for chronic pain relief than sham acupuncture in adults with CNP, and
to determine which type of sham acupuncture is the optimal control for clinical
trials. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR-IOR-15006886
. Registered on 2 July 2015.
PMID- 28693564
TI - Surveillance of recent HIV infections among newly diagnosed HIV cases in Germany
between 2008 and 2014.
AB - BACKGROUND: The HIV surveillance system in Germany is based on mandatory,
anonymous notification of newly diagnosed HIV cases by laboratories. Because the
time between HIV infection and the diagnosis of HIV varies widely between
persons, it is difficult to determine the number of cases of recent HIV infection
among newly diagnosed cases of HIV. In Germany, the BED-capture-enzyme
immunoassay (BED-CEIA) has been used to distinguish between recent and long
standing HIV infection. The aim of this analysis is to report the proportion of
cases of recent HIV infection among newly diagnosed cases in Germany between 2008
and 2014 and to identify factors associated with recent infections. METHODS: A
sample of voluntary laboratories among all HIV diagnostic laboratories was
recruited. Residual blood from HIV diagnostic tests was spotted on filter paper
as dried serum or dried plasma spots and was sent along with the notification
form of the HIV cases. The BED-CEIA test was performed. A case was defined as
recent HIV infection with a BED-CEIA test result of less than 0.8 normalized
optical density, with the exclusion of CDC stage C. The proportion of recent
newly diagnosed HIV infections among different groups (such as transmission
groups, gender or age groups) was calculated. We used logistic regression to
identify factors associated with recent HIV infection and to identify
subpopulations with high proportions of recent HIV infections. RESULTS:
Approximately 10,257 newly diagnosed cases were tested for recency using the BED
CEIA. In total, 3084 (30.4%) of those were recently infected with HIV. The
highest proportion of recent HIV infections was found among men who had sex with
men (MSM) (35%) and persons between 18 and 25 years of age (43.0%). Logistic
regression revealed that female German intravenous drug users with a recent HIV
infection had a higher chance of being detected than German MSM (OR 2.27).
CONCLUSIONS: Surveillance of recent HIV infection is a useful additional tool to
monitor the HIV epidemic in Germany. We could observe ongoing HIV transmission in
Germany in general and in different subgroups, and we could identify factors
associated with recent HIV infection in Germany.
PMID- 28693565
TI - Two-year post-discharge costs of care among patients treated with transcatheter
or surgical aortic valve replacement in Germany.
AB - BACKGROUND: This study presents data on post-discharge costs of care among
patients treated with transcatheter or surgical aortic valve replacement over a
two year period. METHODS: Based on a prospective clinical trial, post-discharge
utilization of health services and status of assistance were collected for 151
elderly patients via 2250 monthly telephone interviews, valued using standardized
unit costs and analysed using two-part regression models. RESULTS: At month 1
post-discharge, total costs of care are substantially elevated (monthly mean:
?3506.7) and then remain relatively stable over the following 23 months (monthly
mean: ?622.3). As expected, the majority of these costs are related to in
hospital care (~98% in month 1 post-discharge and ~72% in months 2-24). Patients
that died during follow-up were associated with substantially higher cost
estimates of in-hospital care than those surviving the two-year study period,
while patients' age and other patient characteristics were of minor relevance.
Estimated costs of outpatient care are lower at month 1 than during the rest of
the study period, and not affected by the event of death during follow-up. The
estimated costs of nursing care are, in contrast, much higher in year 2 than in
year 1 and differ substantially by gender and type of procedure as well as by
patients' age. Overall, these monthly cost estimates add up to ?10,352 for the
first and ?7467.6 for the second year post-discharge. CONCLUSIONS: Substantial
cost increases at month 1 post-discharge and in case of death during follow-up
are the main findings of the study, which should be taken into account in future
economic evaluations on the topic. Application of standardized unit costs in
combination with monthly patient interviews allows for a far more precise
estimate of the variability in post-discharge health service utilization in this
group of patients than the ones given in previous studies. TRIAL REGISTRATION:
German Clinical Trial Register Nr. DRKS00000797 .
PMID- 28693566
TI - Medical student and medical school teaching faculty perceptions of conflict of
interest.
AB - BACKGROUND: Attitudes towards conflict of interest (COI) and COI policy are
shaped during medical school and influence both the education of medical students
and their future medical practice. Understanding the current attitudes of medical
students and medical school teaching faculty may provide insight into what is
taught about COI and COI policy within the 'hidden' medical curriculum.
Differences between medical student and medical school teaching faculty
perceptions of COI and COI policy have not been compared in detail. The authors
surveyed first year medical students and medical school teaching faculty at one
academic medical center. RESULTS: The response rate was 98.7% (150/152) for
students and 34.2% (69/202) for faculty. Students were less likely than faculty
to agree that lecturers should disclose COI to any learners (4.06 vs. 4.31, p =
0.01), but more likely to agree that COI disclosure decreases the presentation of
biased material (3.80 vs. 3.21, p < 0.001). Student and faculty responses for all
other questions were not different. Many of these responses suggest student and
faculty support for stronger COI policy at academic medical centers. CONCLUSIONS:
Students and faculty perceptions regarding COI and COI policy are largely
similar, but differ in terms of the perceived effectiveness of COI disclosure.
This study also suggests that medical students and medical school teaching
faculty support for stronger COI policy at academic medical centers.
PMID- 28693567
TI - Protocol based invasive intracranial pressure monitoring in acute liver failure:
feasibility, safety and impact on management.
AB - BACKGROUND: Acute liver failure (ALF) may result in elevated intracranial
pressure (ICP). While invasive ICP monitoring (IICPM) may have a role in ALF
management, these patients are typically coagulopathic and at risk for
intracranial hemorrhage (ICH). Contemporary ICP monitoring techniques and
coagulopathy reversal strategies may be associated with a lower risk of
hemorrhage. Our objective was to evaluate the safety, feasibility, impact on
clinical management and outcomes associated with protocol-directed use of IICPM
in ALF. METHODS: Adult patients admitted between June 2011 and October 2016, with
ALF and grade-4 encephalopathy with a reasonable likelihood of survival, were
eligible for IICPM. The coagulopathy reversal protocol included administration of
recombinant Factor VIIa (rFVIIa) and desmopressin, a goal platelet count
>50,000/mm3 and fibrinogen >100 mg/dL. Monitor insertion was performed within an
hour of the rFVIIa dose. Only intraparenchymal monitors were used. Computed
tomography of the brain was performed prior to and within 24 hours of monitor
placement. Outcomes of interest included ICH, sustained intracranial
hypertension, therapeutic intensity level (TIL) for ICP management, mortality and
functional outcome on the Glasgow Outcome Scale (GOS) at discharge and 6 months.
RESULTS: A total of 24/37 patients (65%) with ALF underwent IICPM. The most
common reason for exclusion was encephalopathy grade <4. Four patients underwent
liver transplantation. There was one asymptomatic ICH following IICPM, in a
patient who had an excellent outcome. Sustained intracranial hypertension
occurred in 13/24 monitored patients (54%), 5/24 (21%) required extreme measures
(TIL-4) for ICP control, which were successful in 4 patients: 12/24 patients
(50%) died but only 4 deaths (17%) were attributed to intracranial hypertension.
Six of the 8 survivors with 6-month follow up had good functional outcome (GOS
>3). CONCLUSIONS: Protocol-directed use of IICPM in ALF is feasible, associated
with a low incidence of serious complications and has a significant impact on
clinical management.
PMID- 28693568
TI - Anorexia nervosa and cancer: a protocol for a systematic review and meta-analysis
of observational studies.
AB - BACKGROUND: Anorexia nervosa is characterized by a severe restriction of caloric
intake, low body weight, fear of gaining weight or of becoming fat, and
disturbance of body image. Pathogenesis of the disorder may include genetic
predisposition, hormonal changes and a combination of environmental,
psychosocial, and cultural factors. Cancer is the second leading cause of death
worldwide. At present, no systematic reviews and meta-analyses have evaluated the
risk of cancer in people with anorexia nervosa. The objective of this study will
be to evaluate the association between anorexia nervosa and the risk of
developing or dying from cancer. METHODS/DESIGN: This study protocol is part of a
systematic collection and assessment of multiple systematic reviews and meta
analyses (umbrella review) evaluating the association of cancer and multiple
central nervous system disorders. We designed a specific protocol for a new
systematic review and meta-analysis of observational studies of anorexia nervosa
with risk of developing or dying from any cancer. Data sources will be PubMed,
Embase, Scopus, Web of Science, and manual screening of references. Observational
studies (case-control and cohort) in humans that examined the association between
anorexia nervosa and risk of developing or dying from cancer will be sought. The
primary outcomes will be cancer incidence and cancer mortality in association
with anorexia nervosa. Secondary outcomes will be site-specific cancer incidence
and mortality, respectively. Screening of abstracts and full texts, and data
abstraction will be performed by two team members independently. Conflicts at all
levels of screening and abstraction will be resolved through discussion. The
quality of studies will be assessed by using the Ottawa-Newcastle scale by two
team members independently. Random effects models will be conducted where
appropriate. Subgroup and additional analyses will be conducted to explore the
potential sources of heterogeneity. The World Cancer Research Fund
(WCRF)/American Institute for Cancer Research (AICR) criteria and the Grading of
Recommendations Assessment, Development and Evaluation (GRADE) approach will be
used for determining the quality of evidence for cancer outcomes. DISCUSSION:
Findings from this systematic review will inform an ongoing umbrella review on
cancer and central nervous system disorders. Our systematic review and meta
analysis of observational studies will establish the extent of the
epidemiological evidence underlying the association between anorexia nervosa and
cancer. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42017067462.
PMID- 28693569
TI - Validation of an instrument to assess the delivery of patient-centred care to
people with intellectual disabilities as perceived by professionals.
AB - BACKGROUND: Patient/Person Centred Care (PCC) has achieved widespread attention
which resulted in the identification of eight dimensions of PCC: Respect for the
patients' values, preferences and expressed needs; information and education;
access to care; emotional support to relieve fear and anxiety; involvement of
family and friends; continuity and secure transition between healthcare settings;
physical comfort; coordination of care. An instrument to assess patient
centeredness of care delivery according to these eight dimensions among
professionals is however lacking. The main objective of this study is therefore
to develop and validate an instrument to assess the eight PCC dimensions among
professionals providing care to institutionalized People With Intellectual
Disabilities (PWIDs). METHODS: This cross-sectional survey study was conducted in
a disability care centre in the region Twente in the Netherlands, the Twentse
Zorgcentra. All professionals delivering care to institutionalized PWIDs (n =
1146) were invited to participate. An instrument was developed to assess the
eight dimensions of PCC, which was tested among 464 professionals (response rate
= 40%). We tested the instrument by means of structural equation modelling, and
examined its validity and reliability. RESULTS: Indices of the 35-item PCC
version are satisfactory but showed that the model left room for improvement and
shortening of the instrument (RMSEA >0.06 and CFI < 0.95). Confirmatory factor
analyses revealed good indices of fit with the 24-item PCC-instrument among
professionals. Internal consistency of the overall instrument was also good.
CONCLUSIONS: The psychometric properties of the 24-item PCC-instrument were
satisfactory, rendering it a valid and reliable instrument for assessing the
eight dimensions of PCC among professionals providing care to institutionalized
PWIDs.
PMID- 28693570
TI - An analysis of free-choice electives in an undergraduate medical degree.
AB - BACKGROUND: The University College Dublin Elective Programme was introduced in
2005 with the intention of broadening the learning of its undergraduate students.
Undergraduate medical students undertake seven free-choice electives during their
six-year degree programme. They are permitted to choose electives from any school
in the University. Students also have the option of selecting 'In-Programme'
electives, which are aligned to medical themes. The purpose of this study is to
analyse the electives taken by medical students with a view to better
understanding the factors that influence their choices. METHODS: In this mixed
methodology study, the quantitative phase consisted of a retrospective analysis
of 3318 elective choices associated with 474 medical students between 2006 and
2013. Elective choices were analysed in terms of popularity, difficulty level and
subject matter. The prospective qualitative phase consisted of a series of semi
structured focus groups held with current medical students. Discussions from the
focus groups underwent thematic analysis with a few to exploring and clarifying
the quantitative findings. RESULTS: The most frequently chosen electives were In
Programme (38.6%) and Applied Language (21.6%) electives, with patterns not
significantly varying from year to year. Male and female students tended to take
the same type of electives. Focus group discussions revealed that the primary
factor motivating choice was workload, with students preferring less demanding
electives. Participants indicated that elective grading and assessment criteria
had a significant impact on their choices. Participants described ways in which
the elective selection process could be improved, including a desire for more
structured electives and a revision of the elective selection process.
CONCLUSIONS: The retrospective data analysis revealed a high level of consistency
in medical students' elective choices from stage to stage and between different
year cohorts. Qualitative investigation revealed that medical students tend to
focus on grading, assessment strategies and skills development when choosing
their electives. The implication that students may be reluctant to take more
challenging electives despite having an interest in the subject is one that
warrants consideration when designing or adapting programmes for the future.
Although these findings are associated with a free-choice elective programme,
similar strategies are likely to be employed for the more traditional option
based programmes that are associated with the majority of medical degrees
internationally.
PMID- 28693571
TI - Characterization of erythrose reductase from Yarrowia lipolytica and its
influence on erythritol synthesis.
AB - BACKGROUND: Erythritol is a natural sweetener that is used in the food industry.
It is produced as an osmoprotectant by bacteria and yeast. Due to its chemical
properties, it does not change the insulin level in the blood, and therefore it
can be safely used by diabetics. Previously, it has been shown that erythrose
reductase (ER), which catalyzes the final step, plays a crucial role in
erythritol synthesis. ER reduces erythrose to erythritol with NAD(P)H as a
cofactor. Despite many studies on erythritol synthesis by Yarrowia lipolytica,
the enzymes involved in this metabolic pathway have ever been described. RESULTS:
The gene YALI0F18590g encoding the predicted erythrose reductase from Y.
lipolytica was overexpressed, and its influence on erythritol synthesis was
studied. The amino acid sequence of the Y. lipolytica ER showed a high degree of
similarity to the previously described erythrose reductases from known erythritol
producers, such as Candida magnoliae and Moniliella megachiliensis. Here, we
found that the gene overexpression results in an enhanced titer of erythritol of
44.44 g/L (20% over the control), a yield of 0.44 g/g and productivity of 0.77
g/L/h. Moreover, on purification and characterization of the enzyme we found that
it displays the highest activity at 37 degrees C and pH 3.0. The effects of
various metal ions (Zn2+, Cu2+, Mn2+, Fe2+) on erythrose reductase were
investigated. The addition of Zn2+ ions at 0.25 mM had a positive effect on the
activity of erythrose reductase from Y. lipolytica, as well as on the erythritol
production. CONCLUSIONS: In this study we identified, overexpressed and
characterized a native erythrose reductase in Y. lipolytica. Further
optimizations of this strain via metabolic pathway engineering and media
optimization strategies enabled 54 g/L to be produced in a shake-flask
experiment. To date, this is the first reported study employing metabolic
engineering of the native gene involved in the erythritol pathway to result in a
high titer of the polyol. Moreover, it indicates the importance of environmental
conditions for genetic targets in metabolic engineering.
PMID- 28693572
TI - Sex difference in thermal preference of adult mice does not depend on presence of
the gonads.
AB - BACKGROUND: The thermoneutral zone (TNZ) is a species-specific range of ambient
temperature (T a), at which mammals can maintain a constant body temperature with
the lowest metabolic rate. The TNZ for an adult mouse is between 26 and 34
degrees C. Interestingly, female mice prefer a higher T a than male mice although
the underlying mechanism for this sex difference is unknown. Here, we tested
whether gonadal hormones are dominant factors controlling temperature preference
in male and female mice. METHODS: We performed a temperature preference test in
which 10-week-old gonadectomized and sham-operated male and female C57BL/6J mice
were allowed to choose to reside at the thermoneutral cage of 29 degrees C or an
experimental cage of 26, 29, or 32 degrees C. RESULTS: All mice preferred a T a
higher than 26 degrees C, especially in the inactive phase. Choosing between 29
and 32 degrees C, female mice resided more at 32 degrees C while male mice had
no preference between the temperatures. Hence, the preferred T a for female mice
was significantly higher (0.9 +/- 0.2 degrees C) than that for male mice.
However, gonadectomy did not influence the T a preference. CONCLUSIONS: Female
mice prefer a warmer environment than male mice, a difference not affected by
gonadectomy. This suggests that thermal-sensing mechanisms may be influenced by
sex-specific pathways other than gonadal factors or that the thermoregulatory set
point has already been determined prior to puberty.
PMID- 28693573
TI - A qualitative assessment of an abstinence-oriented therapeutic community for
prisoners with substance use disorders in Kyrgyzstan.
AB - BACKGROUND: Kyrgyzstan, where HIV is concentrated in prisons and driven by
injection drug use, provides a prison-based methadone maintenance therapy program
as well as abstinence-oriented therapeutic community based on the 12-step model
called the "Clean Zone." We aimed to qualitatively assess how prisoners navigate
between these treatment options to understand the persistence of the Clean Zone
despite a lack of evidence to support its effectiveness in treating opioid use
disorders. METHODS: We conducted an analysis of policy documents and over 60 h of
participant observation in February 2016, which included focus groups with a
convenience sample of 20 therapeutic community staff members, 110 prisoners
across three male and one female prisons, and qualitative interviews with two
former Clean Zone participants. Field notes containing verbatim quotes from
participants were analyzed through iterative reading and discussion to understand
how participants generally perceive the program, barriers to entry and retention,
and implications for future treatment within prisons. RESULTS: Our analyses
discerned three themes: pride in the mission of the Clean Zone, idealism
regarding addiction treatment outcomes against all odds, and the demonization of
methadone. CONCLUSION: Despite low enrollment and lack of an evidence base, the
therapeutic community is buttressed by the strong support of the prison
administration and its clients as an "ordered" alternative to what is seen as
chaotic life outside of the Clean Zone. The lack of services for Clean Zone
patients after release likely contributes to high rates of relapse to drug use.
The Clean Zone would benefit from integration of stabilized methadone patients
combined with a post-release program.
PMID- 28693574
TI - Demographics of dogs, cats, and rabbits attending veterinary practices in Great
Britain as recorded in their electronic health records.
AB - BACKGROUND: Understanding the distribution and determinants of disease in animal
populations must be underpinned by knowledge of animal demographics. For
companion animals, these data have been difficult to collect because of the
distributed nature of the companion animal veterinary industry. Here we describe
key demographic features of a large veterinary-visiting pet population in Great
Britain as recorded in electronic health records, and explore the association
between a range of animal's characteristics and socioeconomic factors. RESULTS:
Electronic health records were captured by the Small Animal Veterinary
Surveillance Network (SAVSNET), from 143 practices (329 sites) in Great Britain.
Mixed logistic regression models were used to assess the association between
socioeconomic factors and species and breed ownership, and preventative health
care interventions. Dogs made up 64.8% of the veterinary-visiting population,
with cats, rabbits and other species making up 30.3, 2.0 and 1.6% respectively.
Compared to cats, dogs and rabbits were more likely to be purebred and younger.
Neutering was more common in cats (77.0%) compared to dogs (57.1%) and rabbits
(45.8%). The insurance and microchipping relative frequency was highest in dogs
(27.9 and 53.1%, respectively). Dogs in the veterinary-visiting population
belonging to owners living in least-deprived areas of Great Britain were more
likely to be purebred, neutered, insured and microchipped. The same association
was found for cats in England and for certain parameters in Wales and Scotland.
CONCLUSIONS: The differences we observed within these populations are likely to
impact on the clinical diseases observed within individual veterinary practices
that care for them. Based on this descriptive study, there is an indication that
the population structures of companion animals co-vary with human and
environmental factors such as the predicted socioeconomic level linked to the
owner's address. This 'co-demographic' information suggests that further studies
of the relationship between human demographics and pet ownership are warranted.
PMID- 28693575
TI - Interleukin-2 enhancer binding factor 2 interacts with the nsp9 or nsp2 of
porcine reproductive and respiratory syndrome virus and exerts negatively
regulatory effect on the viral replication.
AB - BACKGROUND: Porcine reproductive and respiratory syndrome virus (PRRSV) causes
reproductive failures in sows and respiratory diseases in growing pigs, resulting
in huge economic loss for the pig production worldwide. The nonstructural protein
9 (nsp9) and nonstructural protein 2 (nsp2) of PRRSV are known to play important
roles in viral replication. Cellular interleukin-2 enhancer binding factor 2
(ILF2) participates in many cellular pathways and involves in life cycle of some
viruses. In the present study, we analyzed the interaction of cellular ILF2 with
the nsp9 and nsp2 of PRRSV in vitro and explored the effect of ILF2 on viral
replication. METHODS: The interaction of ILF2 with the nsp9 or nsp2 of PRRSV was
analyzed in 293FT cells and MARC-145 cells by co-immunoprecipitation (Co-IP) and
the co-localization of ILF2 with the nsp9 or nsp2 of PRRSV in MARC-145 cell and
pulmonary alveolar macrophages (PAMs) was examined by confocal immunofluorescence
assay. The effect of ILF2 knockdown and over-expression on PRRSV replication was
explored in MARC-145 cells by small interfering RNA (siRNA) and lentivirus
transduction, respectively. RESULTS: The interaction of ILF2 with nsp9 or nsp2
was first demonstrated in 293FT cells co-transfected with ILF2-expressing plasmid
and nsp9-expressing plasmid or nsp2-expressing plasmid. The interaction of
endogenous ILF2 with the nsp9 or nsp2 of PRRSV was further confirmed in MARC-145
cells transduced with GFP-nsp9-expressing lentiviruses or infected with PRRSV
JXwn06. The RdRp domain of nsp9 was shown to be responsible for its interaction
with ILF2, while three truncated nsp2 were shown to interact with ILF2. Moreover,
we observed that ILF2 partly translocated from the nucleus to the cytoplasm and
co-localized with nsp9 and nsp2 in PRRSV-infected MARC-145 cells and PAMs.
Finally, our analysis indicated that knockdown of ILF2 favored the replication of
PRRSV, while over-expression of ILF2 impaired the viral replication in MARC-145
cells. CONCLUSION: Our findings are the first to confirm that the porcine ILF2
interacts with the nsp9 and nsp2 of PRRSV in vitro, and exerts negatively
regulatory effect on the replication of PRRSV. Our present study provides more
evidence for understanding the roles of the interactions between cellular
proteins and viral proteins in the replication of PRRSV.
PMID- 28693576
TI - Cell-based cytotoxicity assays for engineered nanomaterials safety screening:
exposure of adipose derived stromal cells to titanium dioxide nanoparticles.
AB - BACKGROUND: Increasing production of nanomaterials requires fast and proper
assessment of its potential toxicity. Therefore, there is a need to develop new
assays that can be performed in vitro, be cost effective, and allow faster
screening of engineered nanomaterials (ENMs). RESULTS: Herein, we report that
titanium dioxide (TiO2) nanoparticles (NPs) can induce damage to adipose derived
stromal cells (ADSCs) at concentrations which are rated as safe by standard
assays such as measuring proliferation, reactive oxygen species (ROS), and
lactate dehydrogenase (LDH) levels. Specifically, we demonstrated that low
concentrations of TiO2 NPs, at which cellular LDH, ROS, or proliferation profiles
were not affected, induced changes in the ADSCs secretory function and
differentiation capability. These two functions are essential for ADSCs in wound
healing, energy expenditure, and metabolism with serious health implications in
vivo. CONCLUSIONS: We demonstrated that cytotoxicity assays based on specialized
cell functions exhibit greater sensitivity and reveal damage induced by ENMs that
was not otherwise detected by traditional ROS, LDH, and proliferation assays. For
proper toxicological assessment of ENMs standard ROS, LDH, and proliferation
assays should be combined with assays that investigate cellular functions
relevant to the specific cell type.
PMID- 28693577
TI - Somatoform dissociation and posttraumatic stress syndrome - two sides of the same
medal? A comparison of symptom profiles, trauma history and altered affect
regulation between patients with functional neurological symptoms and patients
with PTSD.
AB - BACKGROUND: History of traumatic experience is common in dissociative disorder
(DD), and similarity of symptoms and characteristics between DD and posttraumatic
stress disorder (PTSD) encouraged to consider DD as trauma-related disorder.
However, conceptualization of DD as a trauma-related syndrome would critically
affect diagnosis and treatment strategies. The present study addressed overlap
and disparity of DD and PTSD by directly comparing correspondence of symptoms,
adverse/traumatic experience, and altered affect regulation between patients
diagnosed with dissociative disorder (characterized by negative functional
neurological symptoms) and patients diagnosed with PTSD. METHODS: Somatoform and
psychoform dissociation, symptoms of posttraumatic stress, general childhood
adversities and lifetime traumata, and alexithymia as index of altered affect
regulation were screened with standardized questionnaires and semi-structured
interviews in 60 patients with DD (ICD-codes F44.4, F44.6, F44.7), 39 patients
with PTSD (ICD-code F43.1), and 40 healthy comparison participants (HC). RESULTS:
DD and PTSD patients scored higher than HC on somatoform and psychoform
dissociative symptom scales and alexithymia, and reported more childhood
adversities and higher trauma load. PTSD patients reported higher symptom
severity and more traumata than DD patients. Those 20 DD patients who met
criteria of co-occuring PTSD did not differ from PTSD patients in the amount of
reported symptoms of somatoform dissociation, physical and emotional childhood
adversities and lifetime traumata, while emotional neglect/abuse in childhood
distinguished DD patients with and without co-occuring PTSD (DD patients with co
occuring PTSD reporting more emotional maltreatment). CONCLUSION: The pattern of
distinctive somatoform and psychoform dissociative symptom severity, type of
childhood and lifetime traumata, and amount of alexithymia suggests that DD and
PTSD are distinctive syndromes and, therefore, challenges the conceptualization
of DD as trauma-related disorder. Together with the detected close correspondence
of symptom and experience profiles in DD patients with co-occuring PTSD and PTSD
patients, these findings suggest that adverse/traumatic experience may intensify
dissociative symptoms, but are not a necessary condition in the generation of
functional neurological symptoms. Still, diagnosis and treatment of DD need to
consider this impact of traumata and post-traumatic stress symptoms.
PMID- 28693578
TI - First detection of European bat lyssavirus type 2 (EBLV-2) in Norway.
AB - BACKGROUND: In Europe, bat rabies is primarily attributed to European bat
lyssavirus type 1 (EBLV-1) and European bat lyssavirus type 2 (EBLV-2) which are
both strongly host-specific. Approximately thirty cases of infection with EBLV-2
in Daubenton's bats (Myotis daubentonii) and pond bats (M. dasycneme) have been
reported. Two human cases of rabies caused by EBLV-2 have also been confirmed
during the last thirty years, while natural spill-over to other non-flying
mammals has never been reported. Rabies has never been diagnosed in mainland
Norway previously. CASE PRESENTATION: In late September 2015, a subadult male
Daubenton's bat was found in a poor condition 800 m above sea level in the
southern part of Norway. The bat was brought to the national Bat Care Centre
where it eventually displayed signs of neurological disease and died after two
days. EBLV-2 was detected in brain tissues by polymerase chain reaction (PCR)
followed by sequencing of a part of the nucleoprotein gene, and lyssavirus was
isolated in neuroblastoma cells. CONCLUSIONS: The detection of EBLV-2 in a bat in
Norway broadens the knowledge on the occurrence of this zoonotic agent. Since
Norway is considered free of rabies, adequate information to the general public
regarding the possibility of human cases of bat-associated rabies should be
given. No extensive surveillance of lyssavirus infections in bats has been
conducted in the country, and a passive surveillance network to assess rabies
prevalence and bat epidemiology is highly desired.
PMID- 28693579
TI - Hospital daily outpatient visits forecasting using a combinatorial model based on
ARIMA and SES models.
AB - BACKGROUND: Accurate forecasting of hospital outpatient visits is beneficial for
the reasonable planning and allocation of healthcare resource to meet the medical
demands. In terms of the multiple attributes of daily outpatient visits, such as
randomness, cyclicity and trend, time series methods, ARIMA, can be a good choice
for outpatient visits forecasting. On the other hand, the hospital outpatient
visits are also affected by the doctors' scheduling and the effects are not pure
random. Thinking about the impure specialty, this paper presents a new
forecasting model that takes cyclicity and the day of the week effect into
consideration. METHODS: We formulate a seasonal ARIMA (SARIMA) model on a daily
time series and then a single exponential smoothing (SES) model on the day of the
week time series, and finally establish a combinatorial model by modifying them.
The models are applied to 1 year of daily visits data of urban outpatients in two
internal medicine departments of a large hospital in Chengdu, for forecasting the
daily outpatient visits about 1 week ahead. RESULTS: The proposed model is
applied to forecast the cross-sectional data for 7 consecutive days of daily
outpatient visits over an 8-weeks period based on 43 weeks of observation data
during 1 year. The results show that the two single traditional models and the
combinatorial model are simplicity of implementation and low computational
intensiveness, whilst being appropriate for short-term forecast horizons.
Furthermore, the combinatorial model can capture the comprehensive features of
the time series data better. CONCLUSIONS: Combinatorial model can achieve better
prediction performance than the single model, with lower residuals variance and
small mean of residual errors which needs to be optimized deeply on the next
research step.
PMID- 28693580
TI - Telemedicine and other care models in pediatric rheumatology: an exploratory
study of parents' perceptions of barriers to care and care preferences.
AB - BACKGROUND: The United States pediatric rheumatology workforce is committed to a
mission of providing children access to pediatric rheumatology care. With a
limited number and distribution of pediatric rheumatologists, telemedicine has
been proposed as one way to meet this mission, yet the adoption of this modality
has been slower than expected. The purpose of this study was to explore the
parent perspective on barriers to accessing pediatric rheumatology care and to
explore the acceptability of telemedicine and other alternative care models.
METHODS: Over a period of six weeks, all new and return English-speaking
parents/guardians of patients visiting a single center were offered an
opportunity to complete a survey which assessed barriers to care and interest in
alternative models of care. Responses were analyzed using descriptive statistics.
RESULTS: Survey response rate was 72% (159/221). Twenty-eight percent (45/159)
traveled more than three hours to the pediatric rheumatology clinic, and 43%
(65/152) reported travel as inconvenient. An overwhelming majority of respondents
(95%, 144/152) reported a preference for in-person visits over the option of
telemedicine. This preference was similar regardless of whether respondents
reported travel to the clinic as inconvenient vs convenient (inconvenient 92%,
60/65; convenient 97%, 84/87; p = 0.2881) and despite those reporting travel as
inconvenient also reporting greater difficulty with several barriers to care.
Those familiar with telemedicine were more likely to report a preference for
telemedicine over in-person visits (27%, 3/11 vs 3%, 4/140; p = 0.0087). The
option of an outreach clinic was acceptable to a majority (63%, 97/154); however,
adult rheumatology and shared-care options were less acceptable (22%, 35/156 and
34%, 53/156 respectively). CONCLUSION: Among survey respondents, in-person visits
were preferred over the option of telemedicine, even when travel was noted to be
inconvenient. Telemedicine familiarity increased its acceptability. Outreach
clinics were acceptable to a majority. Ultimately, the parent perspective can
shape acceptable ways to address barriers and provide accessible care.
PMID- 28693581
TI - Systematic review of control groups in nutrition education intervention research.
AB - BACKGROUND: Well-designed research trials are critical for determining the
efficacy and effectiveness of nutrition education interventions. To determine
whether behavioral and/or cognition changes can be attributed to an intervention,
the experimental design must include a control or comparison condition against
which outcomes from the experimental group can be compared. Despite the impact
different types of control groups can have on study outcomes, the treatment
provided to participants in the control condition has received limited attention
in the literature. METHODS: A systematic review of control groups in nutrition
education interventions was conducted to better understand how control conditions
are described in peer-reviewed journal articles compared with experimental
conditions. To be included in the systematic review, articles had to be indexed
in CINAHL, PubMed, PsycINFO, WoS, and/or ERIC and report primary research
findings of controlled nutrition education intervention trials conducted in the
United States with free-living consumer populations and published in English
between January 2005 and December 2015. Key elements extracted during data
collection included treatment provided to the experimental and control groups
(e.g., overall intervention content, tailoring methods, delivery mode, format,
duration, setting, and session descriptions, and procedures for standardizing,
fidelity of implementation, and blinding); rationale for control group type
selected; sample size and attrition; and theoretical foundation. RESULTS: The
search yielded 43 publications; about one-third of these had an inactive control
condition, which is considered a weak study design. Nearly two-thirds of reviewed
studies had an active control condition considered a stronger research design;
however, many failed to report one or more key elements of the intervention,
especially for the control condition. None of the experimental and control group
treatments were sufficiently detailed to permit replication of the nutrition
education interventions studied. CONCLUSIONS: Findings advocate for improved
intervention study design and more complete reporting of nutrition education
interventions.
PMID- 28693582
TI - Oncogenic miR-210-3p promotes prostate cancer cell EMT and bone metastasis via NF
kappaB signaling pathway.
AB - BACKGROUND: The primary issue arising from prostate cancer (PCa) is its high
prevalence to metastasize to bone, which severely affects the quality of life and
survival time of PCa patients. miR-210-3p is a well-documented oncogenic miRNA
implicated in various aspects of cancer development, progression and metastasis.
However, the clinical significance and biological roles of miR-210-3p in PCa bone
metastasis remain obscure. METHODS: miR-210-3p expression was evaluated by real
time PCR in 68 bone metastatic and 81 non-bone metastatic PCa tissues. The
biological roles of miR-210-3p in the bone metastasis of PCa were investigated
both in vitro by EMT and Transwell assays, and in vivo using a mouse model of
left cardiac ventricle inoculation. Bioinformatics analysis, real-time PCR,
western blot and luciferase reporter analysis were applied to discern and examine
the relationship between miR-210-3p and its potential targets. RT-PCR was
performed to identify the underlying mechanism of miR-210-3p overexpression in
bone metastasis of PCa. Clinical correlation of miR-210-3p with its targets was
examined in human PCa and metastatic bone tissues. RESULTS: miR-210-3p expression
is elevated in bone metastatic PCa tissues compared with non-bone metastatic PCa
tissues. Overexpression of miR-210-3p positively correlates with serum PSA
levels, Gleason grade and bone metastasis status in PCa patients. Upregulating
miR-210-3p enhances, while silencing miR-210-3p represses the EMT, invasion and
migration of PCa cells in vitro. Importantly, silencing miR-210-3p significantly
inhibits bone metastasis of PC-3 cells in vivo. Our results further demonstrate
that miR-210-3p maintains the sustained activation of NF-kappaB signaling via
targeting negative regulators of NF-kappaB signaling (TNF-alpha Induced Protein 3
Interacting Protein 1) TNIP1 and (Suppressor Of Cytokine Signaling 1) SOCS1,
resulting in EMT, invasion, migration and bone metastasis of PCa cells. Moreover,
our results further indicate that recurrent gains (amplification) contribute to
miR-210-3p overexpression in a small number of PCa patients. The clinical
correlation of miR-210-3p with SOCS1, TNIP1 and NF-kappaB signaling activity is
verified in PCa tissues. CONCLUSION: Our findings unravel a novel mechanism for
constitutive activation of NF-kappaB signaling pathway in the bone metastasis of
PCa, supporting a functional and clinical significance of epigenetic events in
bone metastasis of PCa.
PMID- 28693583
TI - Prevention of seasonal affective disorder in daily clinical practice: results of
a survey in German-speaking countries.
AB - BACKGROUND: Seasonal affective disorder (SAD) is a seasonally recurrent type of
major depression. This predictable aspect makes it promising for preventive
treatment. However, evidence for the efficacy and harm of preventive treatment of
SAD is scarce, as are recommendations from clinical practice guidelines. The aim
of this study was to assess the current use of preventive treatment of SAD in
clinical practice in German-speaking countries for the first time. METHODS: We
conducted a postal and web-based survey sent to the heads of all psychiatric
institutions listed in the inventory "Deutsches Krankenhaus Adressbuch, 2015"
that contains all psychiatric hospitals in Germany, Austria, and Switzerland.
RESULTS: One hundred institutions (out of 533 institutions, 19%), which treated
in total more than 3100 SAD patients in the years 2014/2015, responded. Of those,
81 reported recommending preventive treatment to patients with a history of SAD.
There was no consensus on the optimal starting point for preventive treatment.
Most of the institutions that implemented prevention of SAD, recommended
lifestyle changes (85%), antidepressants (84%), psychotherapy (73%), and light
therapy (72%) to their patients. The situation was similar in northern and
southern regions. CONCLUSIONS: Most hospitals recommended the use of preventive
treatment to SAD patients, although evidence on efficacy and harm is limited. A
wide variety of interventions were recommended, although guidelines only include
recommendations for acute treatment. To assist psychiatrists and patients in
future decision making, controlled studies on preventive treatment for SAD that
compare different interventions with one another are needed.
PMID- 28693584
TI - "Long-term stability of stimulating spiral nerve cuff electrodes on human
peripheral nerves".
AB - BACKGROUND: Electrical stimulation of the peripheral nerves has been shown to be
effective in restoring sensory and motor functions in the lower and upper
extremities. This neural stimulation can be applied via non-penetrating spiral
nerve cuff electrodes, though minimal information has been published regarding
their long-term performance for multiple years after implantation. METHODS: Since
2005, 14 human volunteers with cervical or thoracic spinal cord injuries, or
upper limb amputation, were chronically implanted with a total of 50 spiral nerve
cuff electrodes on 10 different nerves (mean time post-implant 6.7 +/- 3.1
years). The primary outcome measures utilized in this study were muscle
recruitment curves, charge thresholds, and percent overlap of recruited motor
unit populations. RESULTS: In the eight recipients still actively involved in
research studies, 44/45 of the spiral contacts were still functional. In four
participants regularly studied over the course of 1 month to 10.4 years, the
charge thresholds of the majority of individual contacts remained stable over
time. The four participants with spiral cuffs on their femoral nerves were all
able to generate sufficient moment to keep the knees locked during standing after
2-4.5 years. The dorsiflexion moment produced by all four fibular nerve cuffs in
the active participants exceeded the value required to prevent foot drop, but no
tibial nerve cuffs were able to meet the plantarflexion moment that occurs during
push-off at a normal walking speed. The selectivity of two multi-contact spiral
cuffs was examined and both were still highly selective for different motor unit
populations for up to 6.3 years after implantation. CONCLUSIONS: The spiral nerve
cuffs examined remain functional in motor and sensory neuroprostheses for 2-11
years after implantation. They exhibit stable charge thresholds, clinically
relevant recruitment properties, and functional muscle selectivity. Non
penetrating spiral nerve cuff electrodes appear to be a suitable option for long
term clinical use on human peripheral nerves in implanted neuroprostheses.
PMID- 28693585
TI - Controlled automated reperfusion of the whole body after 120 minutes of
Cardiopulmonary resuscitation: first clinical report.
AB - BACKGROUND: Cardiopulmonary resuscitation (CPR) is associated with a high
mortality rate. Furthermore, the few survivors often have severe, persistent
cerebral dysfunction. A potential cause for this unsatisfactory outcome after CPR
is the combination of cardiac arrest (ischemia) and the inability to restore
adequate hemodynamics during conventional CPR (reperfusion), resulting in
ischemia/reperfusion injury of the whole body. Therefore we developed a concept
counteracting this ischemia/reperfusion injury during the process of CPR. CASE
PRESENTATION: We present data from a patient, in whom the concept of a novel
controlled automated reperfusion of the whole body (CARL) was applied after 120
min of CPR under normothermic conditions. The patient survived without cerebral
deficits and showed full recovery of all organs after prolonged cardiac arrest
(CA) except for the spinal cord, where a defect at the level of the 11th thoracic
vertebra caused partial loss of motoric function of the legs. CONCLUSION: This is
the first reported clinical application of CARL after CA. The implementation of
CARL resulted in unexpected survival and recovery after prolonged normothermic CA
and CPR. In synopsis with the preclinical experience in pigs this case shows,
that the new concept of CARL treating ischemia/reperfusion during the CPR may be
an important element within the future treatment of CA. TRIAL REGISTRATION: Trial
was retrospectively registered in the "German Clinical Trials Register" (
www.germanctr.de ) under No.: DRKS00005773 on July 28th, 2015.
PMID- 28693586
TI - Impaired B cell immunity in acute myeloid leukemia patients after chemotherapy.
AB - BACKGROUND: Changes in adaptive immune cells after chemotherapy in adult acute
myeloid leukemia (AML) may have implications for the success of immunotherapy.
This study was designed to determine the functional capacity of the immune system
in adult patients with AML who have completed chemotherapy and are potential
candidates for immunotherapy. METHODS: We used the response to seasonal influenza
vaccination as a surrogate for the robustness of the immune system in 10 AML
patients in a complete remission post-chemotherapy and performed genetic,
phenotypic, and functional characterization of adaptive immune cell subsets.
RESULTS: Only 2 patients generated protective titers in response to vaccination,
and a majority of patients had abnormal frequencies of transitional and memory B
cells. B-cell receptor sequencing showed a B-cell repertoire with little evidence
of somatic hypermutation in most patients. Conversely, frequencies of T-cell
populations were similar to those seen in healthy controls, and cytotoxic T-cells
demonstrated antigen-specific activity after vaccination. Effector T-cells had
increased PD-1 expression in AML patients least removed from chemotherapy.
CONCLUSION: Our results suggest that while some aspects of cellular immunity
recover quickly, humoral immunity is incompletely reconstituted in the year
following intensive cytotoxic chemotherapy for AML. The observed B-cell
abnormalities may explain the poor response to vaccination often seen in AML
patients after chemotherapy. Furthermore, the uncoupled recovery of B-cell and T
cell immunity and increased PD-1 expression shortly after chemotherapy might have
implications for the success of several modalities of immunotherapy.
PMID- 28693587
TI - Human presence impacts fungal diversity of inflated lunar/Mars analog habitat.
AB - BACKGROUND: An inflatable lunar/Mars analog habitat (ILMAH), simulated closed
system isolated by HEPA filtration, mimics International Space Station (ISS)
conditions and future human habitation on other planets except for the exchange
of air between outdoor and indoor environments. The ILMAH was primarily
commissioned to measure physiological, psychological, and immunological
characteristics of human inhabiting in isolation, but it was also available for
other studies such as examining its microbiological aspects. Characterizing and
understanding possible changes and succession of fungal species is of high
importance since fungi are not only hazardous to inhabitants but also deteriorate
the habitats. Observing the mycobiome changes in the presence of human will
enable developing appropriate countermeasures with reference to crew health in a
future closed habitat. RESULTS: Succession of fungi was characterized utilizing
both traditional and state-of-the-art molecular techniques during the 30-day
human occupation of the ILMAH. Surface samples were collected at various time
points and locations to observe both the total and viable fungal populations of
common environmental and opportunistic pathogenic species. To estimate the
cultivable fungal population, potato dextrose agar plate counts method was
utilized. The internal transcribed spacer region-based iTag Illumina sequencing
was employed to measure the community structure and fluctuation of the mycobiome
over time in various locations. Treatment of samples with propidium monoazide
(PMA; a DNA intercalating dye for selective detection of viable microbial
populations) had a significant effect on the microbial diversity compared to non
PMA-treated samples. Statistical analysis confirmed that viable fungal community
structure changed (increase in diversity and decrease in fungal burden) over the
occupation time. Samples collected at day 20 showed distinct fungal profiles from
samples collected at any other time point (before or after). Viable fungal
families like Davidiellaceae, Teratosphaeriaceae, Pleosporales, and Pleosporaceae
were shown to increase during the occupation time. CONCLUSIONS: The results of
this study revealed that the overall fungal diversity in the closed habitat
changed during human presence; therefore, it is crucial to properly maintain a
closed habitat to preserve it from deteriorating and keep it safe for its
inhabitants. Differences in community profiles were observed when statistically
treated, especially of the mycobiome of samples collected at day 20. On a genus
level Epiccocum, Alternaria, Pleosporales, Davidiella, and Cryptococcus showed
increased abundance over the occupation time.
PMID- 28693588
TI - CXCL11 production in cerebrospinal fluid distinguishes herpes simplex meningitis
from herpes simplex encephalitis.
AB - BACKGROUND: The closely related herpes simplex viruses 1 and 2 can cause
inflammations of the central nervous system (CNS), where type 1 most often
manifest as encephalitis (HSE), and type 2 as meningitis (HSM). HSE is associated
with severe neurological complications, while HSM is benign in adults. We
proposed that studying the chemokine and cytokine production in cerebrospinal
fluid (CSF) and serum could indicate why two closely related viruses exhibit
different severity of their accompanied CNS inflammation. METHODS: Secretion
patterns of 30 chemokines and 10 cytokines in CSF of adult patients with acute
HSE (n = 14) and HSM (n = 20) in the initial stage of disease were analyzed and
compared to control subjects without viral central nervous system infections and
to levels in serum. RESULTS: Most measured chemokines and cytokines increased in
CSF of HSE and HSM patients. Overall, the CSF chemokine levels were higher in CSF
of HSM patients compared to HSE patients. However, only five chemokines reached
levels in the CSF that exceeded those in serum facilitating a positive CSF-serum
chemokine gradient. Of these, CXCL8, CXCL9, and CXCL10 were present at high
levels both in HSE and HSM whereas CXCL11 and CCL8 were present in HSM alone.
Several chemokines were also elevated in serum of HSE patients but only one in
HSM patients. No chemokine in- or efflux between CSF and serum was indicated as
the levels of chemokines in CSF and serum did not correlate. CONCLUSIONS: We show
that HSM is associated with a stronger and more diverse inflammatory response in
the CNS compared to HSE in the initial stage of disease. The chemokine patterns
were distinguished by the exclusive local CNS production of CXCL11 and CCL8 in
HSM. Inflammation in HSM appears to be restricted to the CNS whereas HSE also was
associated with systemic inflammation.
PMID- 28693589
TI - The recurrent campylobacteriosis epidemic over Christmas and New Year in European
countries, 2006-2014.
AB - OBJECTIVE: Campylobacteriosis is the most frequently reported foodborne disease
in Europe with a notification rate of 71 per 100,000 population in the European
Union in 2014. Surveillance data show a clear seasonality whereby case numbers
peak during summer months in entire Europe and at the turn of the year,
especially in Germany and Switzerland. A detailed description of European
surveillance data by country at the turn of the year was missing so far. The
objectives of the presented work were to describe national surveillance data of
The European Surveillance System for 14 countries during winter times and to
generate hypotheses for the observed seasonality of campylobacteriosis cases.
RESULTS: The analysis included 317,986 cases notified between calendar weeks 45
and 8 of winter seasons 2006/2007-2013/2014. Winter peaks in weekly case
notifications and notification rates were observed for Austria, Belgium, Finland,
Germany, Luxembourg, The Netherlands, Switzerland and Sweden while for Denmark,
France, Ireland, Italy, Norway and the United Kingdom no unusual increase was
observed. Generally, weekly notification rates peaked in calendar week 1 or 2
after a strong decline in the last week of December and reached values of a
multiple of the observed notification rates in the weeks before or after the peak
e.g. up to 6.5 notifications per 100,000 population per week in Luxembourg.
Disease onset of cases notified during winter peaks occurred predominantly in
calendar weeks 52 and 1 and point towards risk exposures around Christmas and New
Year. The consumption of meat fondue or table top grilling poses such a risk and
is popular in many countries with an observed winter peak. Additionally,
increased travel activities over the festive season could foster
campylobacteriosis transmission. Surveillance artefacts (e.g. reporting delays
due to public holidays) should be excluded as causes for country-specific winter
peaks before investigating risk exposures.
PMID- 28693590
TI - Patella morphological alteration after patella instability in growing rabbits.
AB - BACKGROUND: The shape of the patella has been considered to be a predisposing
factor resulting in patellar instability, but the effects of abnormal patella
position during its development are unclear. The present study evaluated patellar
morphological changes after patella instability and evaluated the influence of
patellar instability on the patella shape. METHODS: Twenty rabbits that were 2
months old were included in the study. The left knee of each rabbit, defined as
the experimental group (N = 20 knees/group), underwent a medial soft tissue
restraint release. The right knee of each rabbit, defined as the control group (N
= 20 knees/group), did not undergo any surgical procedures. A CT scan was
performed on each knee before surgery and 6 months post-surgery to measure the
transverse diameter, thickness, Wiberg index, and Wiberg angle for analysis of
the patellar morphological changes. Cross-specimen examination was conducted to
evaluate the differences between the experimental group and the control group.
RESULTS: The four indices remained the same between the two groups before
surgery. However, 6 months after surgery, the mean transverse diameter of the
patellae in the experimental group was significantly longer than that in the
control group (P < 0.001), while the mean thickness in the experimental group was
not significantly greater than that in the control group (P = 0.314), resulting
in a flattened shape. The Wiberg indices were not significantly different between
the two groups. However, the mean Wiberg angle was higher in the experimental
group than in the control group (P < 0.001), which resulted in a flattened
articular surface of the patella. CONCLUSION: The sectional shape and articular
surface of the patella became more flattened after patella instability in this
study, which indicates that patella dysplasia could be caused by patella
instability. Clinically, early intervention for adolescent patients with patella
instability is important.
PMID- 28693591
TI - Aphrodisiac potentials of the ethanol extract of Aloe barbadensis Mill. root in
male Wistar rats.
AB - BACKGROUND: Aloe barbadensis (AB) is a short stemmed succulent medicinal herb
that is being used by locals in Nigeria to enhance libido. Therefore this study
evaluates the aphrodisiac potential and acute toxicological effect of A.
barbadensis (AB) root in male Wistar rats. METHODS: Aphrodisiac potential was
determined following the oral administration of graded doses (100, 200 and 400
mg/kg) of ethanol extract of A. barbadensis root. Sildenafil citrate (Viagra) and
distilled water served as positive and negative controls respectively. Sexual
behavioural parameters (mounting and intromission frequencies, mounting,
intromission and ejaculatory latencies) were observed. Serum testosterone and
cholesterol concentrations were also progressively monitored on days 1, 7 and 14.
The acute toxicological evaluation of the plant were based on any onset
behavioural changes and mortality respectively. RESULTS: The findings from the
sexual behavioural study indicated that the ethanol extract of A. barbadensis
significantly increased mounting frequency and intromission frequency but
significantly decreased mount and intromission latencies in a dose dependent
manner particularly on day 1 and 14. The ethanol extract also prolonged
ejaculatory latency. The testosterone and cholesterol concentrations were also
increased as the dose increased particularly on day 1 and 7. The lowest dose of
100 mg/kg showed the best aphrodisiac effect. The toxicity studies showed that
there were no acute behavioural changes with zero mortality. CONCLUSION: The
increased blood testosterone and cholesterol concentrations by the ethanol
extract of A. barbadensis can probably be said to be the possible mechanisms of
action for its aphrodisiac property. The plant may also be used to treat
hypotestosteronemia following its ability to increase testosterone. These
findings therefore give backing to the acclaimed local use of A. barbadensis root
as an aphrodisiac in males.
PMID- 28693592
TI - Bone metabolism and inflammatory characteristics in 14 cases of chronic
nonbacterial osteomyelitis.
AB - BACKGROUND: Chronic nonbacterial osteomyelitis (CNO) is a multifocal
autoinflammatory disease that often impairs daily life in children. This study
aimed to investigate the bone metabolic and inflammatory characteristics of
patients with CNO, and to assess the differences between responders and
nonresponders to conservative treatment. METHODS: We investigated the clinical
symptoms; laboratory data including inflammatory and bone metabolic biomarkers;
and imaging findings from plain radiography, magnetic resonance imaging (MRI),
fluorodeoxyglucose-positron emission tomography (FDG-PET), and dual-energy x-ray
absorption (DEXA) in 14 patients with CNO. All patients underwent first-line
treatment comprising systemic nonsteroidal anti-inflammatory drugs with or
without bisphosphonate. According to the response to the first-line treatment,
the patients were divided into the clinical remission/partial response group and
the no response group. The differences in bone metabolic and inflammatory
characteristics between the two groups were assessed. RESULTS: All patients had
low bone mineral density assessed with DEXA. The bone metabolic biomarkers (bone
specific alkaline phosphatase and tartrate-resistant acid phosphatase 5b) were
increased in boys of all ages and in young girls. Multiple inflammatory regions
were detected in all patients by using FDG-PET including asymptomatic regions.
The no response group had higher immunoglobulin G (IgG) and a greater number of
bone inflammatory lesions detected on MRI than the clinical remission/partial
response group. CONCLUSION: Our data indicate the involvement of abnormal bone
turnover, necessity of whole-body scanning, and association of higher serum IgG
levels and greater numbers of inflammatory lesions with prolonged disease
activity in patients with CNO.
PMID- 28693593
TI - Psychological stress is related to a decrease of serum anti-mullerian hormone
level in infertile women.
AB - BACKGROUND: Stress exposure has been proved to be linked to reproductive failure.
The reproductive potential of women depends on the ovarian reserve. Anti
mullerian hormone (AMH) has been proved a reliable clinical marker of ovarian
reserve. However, the correlation between psychological stress and AMH level is
not clear. METHODS: A cross-sectional study including 576 women was conducted.
AMH concentration was tested to reflect the ovarian reserve. Salivary alpha
amylase (SAA) level was measured to assess the stress of patients objectively.
RESULTS: The SAA level was significantly, and negatively correlated with AMH
levels in infertile women (r = -0.315, P = 0.000; adjusted for age, r = -0.336, P
= 0.000). CONCLUSION: Higher psychological stress was related to a decreased AMH
level in infertile women and psychological stress may affect ovarian reserve.
PMID- 28693594
TI - The impact of phosphate-balanced crystalloid infusion on acid-base homeostasis
(PALANCE study): study protocol for a randomized controlled trial.
AB - BACKGROUND: This study aims to investigate the effects of a modified, balanced
crystalloid including phosphate in a perioperative setting in order to maintain a
stable electrolyte and acid-base homeostasis in the patient. METHODS/DESIGN: This
is a single-centre, open-label, randomized controlled trial involving two
parallel groups of female patients comparing a perioperative infusion regime with
sodium glycerophosphate and Jonosteril(r) (treatment group) or Jonosteril(r)
(comparator) alone. The primary endpoint is to maintain a stable concentration of
weak acids [A-] according to the Stewart approach of acid-base balance. Secondary
endpoints are measurement of serum phosphate levels, other acid-base parameters
such as the strong ion difference (SID), the onset and severity of postoperative
nausea and vomiting (PONV), electrolyte levels and their excretion in the urine,
monitoring of renal function and glycocalyx components, haemodynamics, amounts of
catecholamines and other vasopressors used and the safety of the infusion regime.
DISCUSSION: Perioperative fluid replacement with the use of currently available
crystalloid preparations still fail to maintain a stable acid-base balance and
experts agree that common balanced solutions are still not ideal. This study aims
to investigate the effectivity and safety of a new crystalloid solution by adding
sodium glycerophosphate to a standardized crystalloid preparation in order to
maintain a balanced perioperative acid-base homeostasis. TRIAL REGISTRATION:
EudraCT number 201002422520 . Registered on 30 November 2010.
PMID- 28693595
TI - Biochemical characterization and 1H NMR based metabolomics revealed Melicope lunu
ankenda leaf extract a potent anti-diabetic agent in rats.
AB - BACKGROUND: Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized
by continuous hyperglycemia associated with insulin resistance and /or reduced
insulin secretion. There is an emerging trend regarding the use of medicinal
plants for the treatment of diabetes mellitus. Melicope lunu-ankenda (ML) is one
of the Melicope species belonging to the family Rutaceae. In traditional
medicines, its leaves and flowers are known to exhibit prodigious health
benefits. The present study aimed at investigating anti-diabetic effect of
Melicope lunu-ankenda (ML) leaves extract. METHODS: In this study, anti-diabetic
effect of ML extract is investigated in vivo to evaluate the biochemical changes,
potential serum biomarkers and alterations in metabolic pathways pertaining to
the treatment of HFD/STZ induced diabetic rats with ML extract using 1H NMR based
metabolomics approach. Type 2 diabetic rats were treated with different doses
(200 and 400 mg/kg BW) of Melicope lunu-ankenda leaf extract for 8 weeks, and
serum samples were examined for clinical biochemistry. The metabolomics study of
serum was also carried out using 1H NMR spectroscopy in combination with
multivariate data analysis to explore differentiating serum metabolites and
altered metabolic pathways. RESULTS: The ML leaf extract (400 mg/kg BW) treatment
significantly increased insulin level and insulin sensitivity of obese diabetic
rats, with concomitant decrease in glucose level and insulin resistance.
Significant reduction in total triglyceride, cholesterol and low density
lipoprotein was also observed after treatment. Interestingly, there was a
significant increase in high density lipoprotein of the treated rats. A decrease
in renal injury markers and activities of liver enzymes was also observed.
Moreover, metabolomics studies clearly demonstrated that, ML extract
significantly ameliorated the disturbance in glucose metabolism, tricarboxylic
acid cycle, lipid metabolism, and amino acid metabolism. CONCLUSION: ML leaf
extract exhibits potent antidiabetic properties, hence could be a useful and
affordable alternative option for the management of T2DM.
PMID- 28693596
TI - Prioritising Responses Of Nurses To deteriorating patient Observations (PRONTO)
protocol: testing the effectiveness of a facilitation intervention in a
pragmatic, cluster-randomised trial with an embedded process evaluation and cost
analysis.
AB - BACKGROUND: Vital signs are the primary indicator of physiological status and for
determining the need for urgent clinical treatment. Yet, if physiological signs
of deterioration are missed, misinterpreted or mismanaged, then critical illness,
unplanned intensive care admissions, cardiac arrest and death may ensue. Although
evidence demonstrates the benefit of early recognition and management of
deteriorating patients, failure to escalate care and manage deteriorating
patients remains a relatively frequent occurrence in hospitals. METHODS/DESIGN: A
pragmatic cluster-randomised controlled trial design will be used to measure
clinical effectiveness and cost of a facilitation intervention to improve nurses'
vital sign measurement, interpretation, treatment and escalation of care for
patients with abnormal vital signs. A cost consequence analysis will evaluate the
intervention cost and effectiveness, and a process evaluation will determine how
the implementation of the intervention contributes to outcomes. We will compare
clinical outcomes and costs from standard implementation of clinical practice
guidelines (CPGs) to facilitated implementation of CPGs. The primary outcome will
be adherence to the CPGs by nurses, as measured by escalation of care as per
organisational policy. The study will be conducted in four Australian major
metropolitan teaching hospitals. In each hospital, eight to ten wards will be
randomly allocated to intervention and control groups. Control wards will receive
standard implementation of CPGs, while intervention wards will receive standard
CPG implementation plus facilitation, using facilitation methods and processes
tailored to the ward context. The intervention will be administered to all
nursing staff at the ward level for 6 months. At each hospital, two types of
facilitators will be provided: a hospital-level facilitator as the lead; and two
ward-level facilitators for each ward. DISCUSSION: This study uses an innovative,
networked approach to facilitation to enable uptake of CPGs. Findings will inform
the intervention utility and knowledge translation measurement approaches. If
successful, the study methodology and intervention has potential for translation
to other health care standards. TRIAL REGISTRATION: Australian New Zealand
Clinical Trials Registry (ANZCTR), ACTRN12616000544471p.
PMID- 28693597
TI - Clinical outcome and risk factors of neonatal sepsis among neonates in Felege
Hiwot referral Hospital, Bahir Dar, Amhara Regional State, North West Ethiopia
2016: a retrospective chart review.
AB - BACKGROUND: Sepsis remains a major cause of morbidity and mortality among
neonates. The risk factors and clinical outcomes of sepsis are poorly understood.
Most cases of sepsis occurred mostly within the first week of newborns life
related to perinatal risk factors. Late onset sepsis is related to hospital
acquired infections which is seen after seven days of age. The purpose of this
study was to assess clinical outcome and risk factors of neonatal sepsis in
Felege Hiwot referral hospital Bahir Dar, North West Ethiopia. RESULTS: Among the
total 225 neonatal charts reviewed; 164 (72.9%) were age less than or equal to 7
days, and 144 (64%) were males. About 29 (12.9%) neonates were with irregular
respiratory signs and 40 (17.8%) had meconium aspiration syndrome. Regarding the
clinical outcome of neonatal sepsis: 189 (84%) were improved after treatment, 9
(4%) were died and 13 (5.8%) referred to other organizations for further
treatment. Respiratory distress syndrome [AOR = 0.258 (0.072-0.930)] and meconium
aspiration syndrome [AOR = 0.1989 (0.059-0.664)] were the determinant factors for
poor outcome of neonatal sepsis. CONCLUSION: The clinical outcome of neonatal
sepsis in Felege Hiwot referral hospital was not satisfactory. The significant
risk factors for poor outcome of neonatal sepsis were respiratory distress
syndrome and meconium aspiration syndrome. Recommendations to improve neonatal
outcome are: performing essential newborn care for all newborns and arranging
appropriate follow up until the end of neonatal period, increasing antenatal care
and early detection and management of neonatal infections or problems.
PMID- 28693598
TI - Clinical manifestations and diagnostic methods in pulmonary angiosarcoma:
protocol for a scoping review.
AB - BACKGROUND: Angiosarcoma involving the lung can represent either primary or
metastatic malignancy. Due to the rarity of this condition, knowledge surrounding
the natural history and clinical presentation is scarce. The aim of this scoping
review is to summarize the existing literature on pulmonary angiosarcoma,
particularly as it pertains to the clinical presentation and ancillary tests used
for diagnosis in addition to histopathology. METHODS: We will conduct a
systematic search using Ovid MEDLINE and EMBASE electronic databases. Two
investigators will independently screen identified titles and abstracts to select
articles reporting on pulmonary angiosarcoma. The data will be summarized in a
narrative fashion and organized according to aspects of epidemiology, risk
factors, clinical presentation, diagnostic methods, and treatment. DISCUSSION:
Scoping reviews are increasingly used to synthesize the evidence on a particular
topic, to identify gaps in the literature, and to determine if future systematic
reviews are feasible. In order to improve the care of patients with angiosarcoma,
earlier recognition and diagnosis is required. This review will be valuable for
highlighting the range of clinical presentations and the role of imaging and
other diagnostic tools in the diagnosis of metastatic and primary pulmonary
angiosarcoma. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration:
CRD42017059052.
PMID- 28693599
TI - Determining the impact of 24/7 phone support on hospital readmissions after
aortic valve replacement surgery (the AVRre study): study protocol for a
randomised controlled trial.
AB - BACKGROUND: Patients undergoing surgical aortic valve replacement (sAVR) have
high rates of 30-day readmissions. They also report a low health-related quality
of life (HRQOL) and elevated anxiety and depression. The aim of the AVRre study
is to determine the efficacy and cost of a 24/7 phone-support intervention in
reducing post-discharge readmissions after sAVR. The nature of the support is to
help patients better understand and self-manage non-urgent symptoms at home.
METHODS/DESIGN: AVRre is a prospective, randomised controlled study comprising 30
days of continuous phone-support intervention and then intermittent follow-up for
the first 12 months. Phone call data from and to patients are evaluated
qualitatively; thus, the study has a mixed-method design. Two hundred and eighty
six patients, aged >18 years, scheduled for a sAVR - singly or in combination
with another procedure - are recruited from locations in southeast Norway.
Patients are randomly assigned to the intervention group, who are purposively
phone-called individually 2 and 9 days after discharge and offered on-demand 24/7
(around-the-clock) telephone support for 30 days post-discharge. The primary
outcome variable is the number of 30-day hospital readmissions. Secondary
outcomes are anxiety and depression symptoms, as measured by the Hospital Anxiety
and Depression Scale, HRQOL and quality-adjusted life years, measured by the
EuroQol (EQ-5D). Intervention and hospital readmission (diagnosis-related groups
(DRGs)/length of stay) for the first year after initial discharge from hospital
are used for a cost-utility analysis. Standard parametric and non-parametric
tests are used for evaluations over time. Analysis of covariance is used to
control for possible differences at baseline. Narratives from phone calls are
transcribed verbatim and analysed using systematic text condensation. DISCUSSION:
A complex 'around-the-clock' intervention within a university hospital-based
setting could be an effective strategy to reduce the high readmission rates to
hospital after sAVR. Furthermore, the AVRre 24/7 phone-support manual can be
adapted to other high-risk surgery populations with high readmission rates. TRIAL
REGISTRATION: ClinicalTrials.gov, NCT02522663 . Registered on 11 August 2015.
PMID- 28693600
TI - Normal breast tissue DNA methylation differences at regulatory elements are
associated with the cancer risk factor age.
AB - BACKGROUND: The underlying biological mechanisms through which epidemiologically
defined breast cancer risk factors contribute to disease risk remain poorly
understood. Identification of the molecular changes associated with cancer risk
factors in normal tissues may aid in determining the earliest events of
carcinogenesis and informing cancer prevention strategies. METHODS: Here we
investigated the impact cancer risk factors have on the normal breast epigenome
by analyzing DNA methylation genome-wide (Infinium 450 K array) in cancer-free
women from the Susan G. Komen Tissue Bank (n = 100). We tested the relation of
established breast cancer risk factors, age, body mass index, parity, and family
history of disease, with DNA methylation adjusting for potential variation in
cell-type proportions. RESULTS: We identified 787 cytosine-guanine dinucleotide
(CpG) sites that demonstrated significant associations (Q value <0.01) with
subject age. Notably, DNA methylation was not strongly associated with the other
evaluated breast cancer risk factors. Age-related DNA methylation changes are
primarily increases in methylation enriched at breast epithelial cell enhancer
regions (P = 7.1E-20), and binding sites of chromatin remodelers (MYC and CTCF).
We validated the age-related associations in two independent populations, using
normal breast tissue samples (n = 18) and samples of normal tissue adjacent to
tumor tissue (n = 97). The genomic regions classified as age-related were more
likely to be regions altered in both pre-invasive (n = 40, P = 3.0E-03) and
invasive breast tumors (n = 731, P = 1.1E-13). CONCLUSIONS: DNA methylation
changes with age occur at regulatory regions, and are further exacerbated in
cancer, suggesting that age influences breast cancer risk in part through its
contribution to epigenetic dysregulation in normal breast tissue.
PMID- 28693601
TI - Effects of the "plate model" as part of dietary intervention on modification of
selected cardiometabolic risk factors in post-myocardial infarction patients:
study protocol for a randomized controlled trial.
AB - BACKGROUND: Cardiovascular disease remains the leading cause of morbidity and
mortality worldwide, and there is a rising global burden. The effects of diet on
cardiometabolic risk factors have been studied extensively. Healthy eating as a
cost-effective approach to risk reduction in post-myocardial infarction patients
is proven to be beneficial, and the "plate model" is one of the practical methods
to achieve this objective. METHODS/DESIGN: The study will be conducted as a
randomized, single-blind, controlled clinical trial for a period of 3 months. A
total of 120 overweight (body mass index >23 kg/m2) inpatients (aged 20-70 years)
with a history of troponin-positive acute coronary syndrome (ACS) within the 1
month preceding the study will be recruited. Simple randomization will be used in
participant allocation. The intervention group will receive the model plate diet.
The control group will be provided with routine dietary advice. Other domains,
such as advice on exercise and lifestyle modification, will be equalized among
patients in both the groups. The visits and evaluations will be done at
recruitment (visit 0), 4 weeks, and 12 weeks after the intervention. The primary
outcome will be a mean body weight reduction of 10%, and the secondary outcomes
will include mean reduction of systolic and diastolic blood pressure, improvement
of anthropometric parameters, and improvement of lipid profile and liver enzymes
in the test group compared with the control group at 12 weeks following the plate
model diet. DISCUSSION: This study protocol is designed to establish the effects
of the plate model diet on modification of cardiometabolic risk factors in
patients with ACS. This will also be a pioneering study designed to investigate
the practicality of the model plate in local settings and in the South Asian
region. TRIAL REGISTRATION: Sri Lanka Clinical Trials Registry identifier:
SLCTR/2016/22. Registered on 22 September 2016 ( http://www.slctr.lk/trials/483
).
PMID- 28693602
TI - House ownership, frequency of illness, fathers' education: the most significant
socio-demographic determinants of poor nutritional status in adolescent girls
from low income households of Lahore, Pakistan.
AB - BACKGROUND: Socio demographic factors besides dietary factors play important role
in determining the health status of an individual. Health and nutritional
Intervention programs stand a greater chance of success if planned, keeping the
socio demographic characteristics of a certain population in focus. The present
study was conducted to identify those socio demographic determinants which have a
significant association with poor nutritional status in adolescent girls
belonging to economically deprived households of Lahore. METHODS: A cross
sectional analytical study of 140 adolescent girls living in the peri urban
communities of Lahore was conducted. Socioeconomic and demographic data of the
participants was recorded through a pretested questionnaire. Body mass index
(BMI), a commonly used anthropometric measurement was taken as an indicator of
nutritional status. Below normal (<18.5 m2) BMI was considered a benchmark of
malnutrition in adolescent girls. Frequencies and percentages for socio
demographic variables were calculated and Fisher Exact test was used to find out
the association of nutritional status with socio-demographic predictors. Stepwise
backward logistic regression analysis was then run to identify the most
significant determinants associated with poor nutritional status in the
adolescents. P < 0.05 was considered statistically significant. RESULTS: Chronic
energy deficiency was highly prevalent among adolescent girls, 58% had BMI < 18.5
m2. Binary regression analysis result showed that the participants who lived in
rented houses (AOR = 3.513; 95% CI = 1.366 to 9.031) who fell ill frequently (AOR
= 2.996; 95% CI = 1.198 to 7.491) whose fathers were illiterate (AOR = 2.941; 95%
CI = 1.187 to 7.287) were at greater odds of having poor nutritional status.
Interestingly, the participants who lived in joint families (AOR = 0.411; 95% CI
= 0.145 to 1.168) and were more frequently food insecure (AOR = 0.431; 95% CI =
0.164 to 1.133) had lesser odds of having poor nutritional status than those who
lived in nuclear families and were food secure. CONCLUSION: Frequency of illness,
house ownership and fathers' education are the determinants positively associated
with poor nutritional status of adolescent girls. Food insecurity and joint
family structure were negatively associated with poor nutritional status. The
study will help in planning interventions for improving nutritional status of
adolescent girls by targeting the significant socio demographic determinants of
poor nutritional status among this group.
PMID- 28693603
TI - Differential requirement for satellite cells during overload-induced muscle
hypertrophy in growing versus mature mice.
AB - BACKGROUND: Pax7+ satellite cells are required for skeletal muscle fiber growth
during post-natal development in mice. Satellite cell-mediated myonuclear
accretion also appears to persist into early adulthood. Given the important role
of satellite cells during muscle development, we hypothesized that the necessity
of satellite cells for adaptation to an imposed hypertrophic stimulus depends on
maturational age. METHODS: Pax7CreER-R26RDTA mice were treated for 5 days with
vehicle (satellite cell-replete, SC+) or tamoxifen (satellite cell-depleted, SC-)
at 2 months (young) and 4 months (mature) of age. Following a 2-week washout,
mice were subjected to sham surgery or 10 day synergist ablation overload of the
plantaris (n = 6-9 per group). The surgical approach minimized regeneration, de
novo fiber formation, and fiber splitting while promoting muscle fiber growth.
Satellite cell density (Pax7+ cells/fiber), embryonic myosin heavy chain
expression (eMyHC), and muscle fiber cross sectional area (CSA) were evaluated
via immunohistochemistry. Myonuclei (myonuclei/100 mm) were counted on isolated
single muscle fibers. RESULTS: Tamoxifen treatment depleted satellite cells by
>=90% and prevented myonuclear accretion with overload in young and mature mice
(p < 0.05). Satellite cells did not recover in SC- mice after overload. Average
muscle fiber CSA increased ~20% in young SC+ (p = 0.07), mature SC+ (p < 0.05),
and mature SC- mice (p < 0.05). In contrast, muscle fiber hypertrophy was
prevented in young SC- mice. Muscle fiber number increased only in mature mice
after overload (p < 0.05), and eMyHC expression was variable, specifically in
mature SC+ mice. CONCLUSIONS: Reliance on satellite cells for overload-induced
hypertrophy is dependent on maturational age, and global responses to overload
differ in young versus mature mice.
PMID- 28693604
TI - Right median nerve electrical stimulation for acute traumatic coma (the Asia Coma
Electrical Stimulation trial): study protocol for a randomised controlled trial.
AB - BACKGROUND: Traumatic brain injury (TBI) has become the most common cause of
death and disability in persons between 15 and 30 years of age, and about 10-15%
of patients affected by TBI will end up in a coma. Coma caused by TBI presents a
significant challenge to neuroscientists. Right median nerve electrical
stimulation has been reported as a simple, inexpensive, non-invasive technique to
speed recovery and improve outcomes for traumatic comatose patients.
METHODS/DESIGN: This multicentre, prospective, randomised (1:1) controlled trial
aims to demonstrate the efficacy and safety of electrical right median nerve
stimulation (RMNS) in both accelerating emergence from coma and promoting long
term outcomes. This trial aims to enrol 380 TBI comatose patients to partake in
either an electrical stimulation group or a non-stimulation group. Patients
assigned to the stimulation group will receive RMNS in addition to standard
treatment at an amplitude of 15-20 mA with a pulse width of 300 MUs at 40 Hz ON
for 20 s and OFF for 40 s. The electrical treatment will last for 8 h per day for
2 weeks. The primary endpoint will be the percentage of patients regaining
consciousness 6 months after injury. The secondary endpoints will be Extended
Glasgow Outcome Scale, Coma Recovery Scale-Revised and Disability Rating Scale
scores at 28 days, 3 months and 6 months after injury; Glasgow Coma Scale,
Glasgow Coma Scale Motor Part and Full Outline of Unresponsiveness scale scores
on day 1 and day 7 after enrolment and 28 days, 3 months and 6 months after
injury; duration of unconsciousness and mechanical ventilation; length of
intensive care unit and hospital stays; and incidence of adverse events.
DISCUSSION: Right median nerve electrical stimulation has been used as a safe,
inexpensive, non-invasive therapy for neuroresuscitation of coma patients for
more than two decades, yet no trial has robustly proven the efficacy and safety
of this treatment. The Asia Coma Electrical Stimulation (ACES) trial has the
following novel features compared with other major RMNS trials: (1) the ACES
trial is an Asian multicentre randomised controlled trial; (2) RMNS therapy
starts at an early stage 7-14 days after the injury; and (3) various assessment
scales are used to evaluate the condition of patients. We hope the ACES trial
will lead to optimal use of right median nerve electrical treatment. TRIAL
REGISTRATION: ClinicalTrials.gov, NCT02645578 . Registered on 23 December 2015.
PMID- 28693605
TI - Scaling up and scaling down the production of galactaric acid from pectin using
Trichoderma reesei.
AB - BACKGROUND: Bioconversion of D-galacturonic acid to galactaric (mucic) acid has
previously been carried out in small scale (50-1000 mL) cultures, which produce
tens of grams of galactaric acid. To obtain larger amounts of biologically
produced galactaric acid, the process needed to be scaled up using a readily
available technical substrate. Food grade pectin was selected as a readily
available source of D-galacturonic acid for conversion to galactaric acid.
RESULTS: We demonstrated that the process using Trichoderma reesei QM6a Deltagar1
udh can be scaled up from 1 L to 10 and 250 L, replacing pure D-galacturonic acid
with commercially available pectin. T. reesei produced 18 g L-1 galactaric acid
from food-grade pectin (yield 1.00 g [g D-galacturonate consumed]-1) when grown
at 1 L scale, 21 g L-1 galactaric acid (yield 1.11 g [g D-galacturonate consumed]
1) when grown at 10 L scale and 14 g L-1 galactaric acid (yield 0.77 g [g D
galacturonate consumed]-1) when grown at 250 L scale. Initial production rates
were similar to those observed in 500 mL cultures with pure D-galacturonate as
substrate. Approximately 2.8 kg galactaric acid was precipitated from the 250 L
culture, representing a recovery of 77% of the galactaric acid in the
supernatant. In addition to scaling up, we also demonstrated that the process
could be scaled down to 4 mL for screening of production strains in 24-well plate
format. Production of galactaric acid from pectin was assessed for three strains
expressing uronate dehydrogenase under alternative promoters and up to 11 g L-1
galactaric acid were produced in the batch process. CONCLUSIONS: The process of
producing galactaric acid by bioconversion with T. reesei was demonstrated to be
equally efficient using pectin as it was with D-galacturonic acid. The 24-well
plate batch process will be useful screening new constructs, but cannot replace
process optimisation in bioreactors. Scaling up to 250 L demonstrated good
reproducibility with the smaller scale but there was a loss in yield at 250 L
which indicated that total biomass extraction and more efficient DSP would both
be needed for a large scale process.
PMID- 28693606
TI - Combined use of serum (1,3)-beta-D-glucan and procalcitonin for the early
differential diagnosis between candidaemia and bacteraemia in intensive care
units.
AB - BACKGROUND: This study aimed to assess the combined performance of serum (1,3)
beta-D-glucan (BDG) and procalcitonin (PCT) for the differential diagnosis
between candidaemia and bacteraemia in three intensive care units (ICUs) in two
large teaching hospitals in Italy. METHODS: From June 2014 to December 2015, all
adult patients admitted to the ICU who had a culture-proven candidaemia or
bacteraemia, as well as BDG and PCT measured closely to the time of the index
culture, were included in the study. The diagnostic performance of BDG and PCT,
used either separately or in combination, was assessed by calculating the
sensitivity, specificity, positive predictive value (PPV), negative predictive
value (NPV), and positive and negative likelihood ratios (LR+ and LR-). Changes
from pre-test probabilities to post-test probabilities of candidaemia and
bacteraemia were inferred from Fagan's nomograms. RESULTS: One hundred and sixty
six patients were included, 73 with candidaemia (44%) and 93 with bacteraemia
(56%). When both markers indicated candidaemia (BDG >=80 pg/ml and PCT <2 ng/ml)
they showed higher PPV (96%) compared to 79% and 66% for BDG or PCT alone,
respectively. When both markers indicated bacteraemia (BDG <80 pg/ml and PCT >=2
ng/ml), their NPV for candidaemia was similar to that of BDG used alone (95% vs.
93%). Discordant BDG and PCT results (i.e. one indicating candidaemia and the
other bacteraemia) only slightly altered the pre-test probabilities of the two
diseases. CONCLUSIONS: The combined use of PCT and BDG could be helpful in the
diagnostic workflow for critically ill patients with suspected candidaemia.
PMID- 28693607
TI - Dynamics of Plasmodium vivax sporogony in wild Anopheles stephensi in a malaria
endemic region of Western India.
AB - BACKGROUND: In global efforts to track mosquito infectivity and parasite
elimination, controlled mosquito-feeding experiments can help in understanding
the dynamics of parasite development in vectors. Anopheles stephensi is often
accepted as the major urban malaria vector that transmits Plasmodium in Goa and
elsewhere in South Asia. However, much needs to be learned about the interactions
of Plasmodium vivax with An. stephensi. As a component of the US NIH
International Center of Excellence for Malaria Research (ICEMR) for Malaria
Evolution in South Asia (MESA), a series of membrane-feeding experiments with
wild An. stephensi and P. vivax were carried out to better understand this vector
parasite interaction. METHODS: Wild An. stephensi larvae and pupae were collected
from curing water in construction sites in the city of Ponda, Goa, India. The
larvae and pupae were reared at the MESA ICEMR insectary within the National
Institute of Malaria Research (NIMR) field unit in Goa until they emerged into
adult mosquitoes. Blood for membrane-feeding experiments was obtained from
malaria patients at the local Goa Medical College and Hospital who volunteered
for the study. Parasites were counted by Miller reticule technique and
correlation between gametocytaemia/parasitaemia and successful mosquito infection
was studied. RESULTS: A weak but significant correlation was found between
patient blood gametocytaemia/parasitaemia and mosquito oocyst load. No
correlation was observed between gametocytaemia/parasitaemia and oocyst infection
rates, and between gametocyte sex ratio and oocyst load. When it came to
development of the parasite in the mosquito, a strong positive correlation was
observed between oocyst midgut levels and sporozoite infection rates, and between
oocyst levels and salivary gland sporozoite loads. Kinetic studies showed that
sporozoites appeared in the salivary gland as early as day 7, post-infection.
CONCLUSIONS: This is the first study in India to carry out membrane-feeding
experiments with wild An. stephensi and P. vivax. A wide range of mosquito
infection loads and infection rates were observed, pointing to a strong interplay
between parasite, vector and human factors. Most of the present observations are
in agreement with feeding experiments conducted with P. vivax elsewhere in the
world.
PMID- 28693608
TI - Temporal analysis of IgG antibody responses to Plasmodium falciparum antigens in
relation to changing malaria epidemiology in a West African setting.
AB - BACKGROUND: Coordinated scaled-up malaria control interventions have
substantially contributed to the dramatic decrease of malaria-related morbidity
and mortality in several endemic countries, including Senegal. However, the
impacts of a given malaria control intervention on vector and parasite
populations, acquired immunity, and disease burden remain very poorly documented
largely due to the lack of continuous surveys. This study took advantage of the
sera bank established as part of the Dielmo longitudinal project to investigate
the dynamics of IgG antibody responses that accompanied the epidemiological
changes resulting from malaria control interventions. Schizonts crude extract of
a local strain of Plasmodium falciparum (Pfsch07/03) was used in ELISA to measure
and compare seroprevalence and magnitude of IgG antibody responses from 2000 to
2012. RESULTS: The prevalence of Pfsch07/03 IgG antibody responses progressively
decreased from 97.25% in 2000 to 57.3% in 2012. The prevalence of Pfsch07/03
antibodies categorized between three different age groups (<7, 7-15, and >15
years) revealed increased seroprevalence with age ranging from 47.19 to 62.67 and
89.45%, respectively in (<7, 7-15, and >15 years) old age groups. A marked drop
in seroprevalence was observed after 2008 and was significant in the younger (<7
years) and intermediate (7-15 years) age groups, unlike older individuals aged
>15 years (p = 1.00). CONCLUSIONS: The study revealed a substantial contribution
of all malaria control interventions to the decrease of IgG antibodies responses
to Pfsch07/03 throughout prevention of human-mosquitos contacts, or reduction of
parasite biomass. The present study demonstrates the wider potential of sero
epidemiological analysis in monitoring changes in malaria transmission resulting
from a given malaria control intervention.
PMID- 28693609
TI - Otolaryngology exposure in a longitudinal integrated clerkship setting.
AB - BACKGROUND: Although 20-40% of primary care complaints are Otolaryngology-Head
and Neck Surgery (OtoHNS) related, little emphasis is placed on OtoHNS
instruction at the undergraduate medical education level. An OtoHNS clerkship
rotation is not required at most Canadian medical schools. Furthermore, at
institutions offering an OtoHNS rotation, less than 20% of students are able to
complete a placement. Given that a large percentage of medical students in Canada
will pursue primary care as a career, there remains a gap in providing OtoHNS
clinical training. During the longitudinal integrated clerkship at the Northern
Ontario School of Medicine (NOSM), students are assigned to one of 14 sites, and
not all have access to an otolaryngologist. This study looks to quantify the
level of exposure students are receiving in OtoHNS at NOSM and to assess their
comfort level with diagnosing and treating common otolaryngologic conditions.
METHODS: A structured 13-item survey was administered to second, third and fourth
year medical students at NOSM. RESULTS: A majority (67.9%) of medical students
surveyed had not observed an otolaryngologist. Furthermore, most students (90.6%)
reported receiving very little OtoHNS classroom based and clinical instruction
during medical school. CONCLUSIONS: A discrepancy exists between the quantity and
breadth of OtoHNS training received in undergraduate medical education and the
volume of OtoHNS encounters in primary care practice. Although geographic
dissemination of students in the distributed learning model may be a challenge,
strategies such as standardized objectives and supplemental electronic resources
may serve to solidify clinical knowledge.
PMID- 28693610
TI - GATA3 is a sensitive marker for primary genital extramammary paget disease: an
immunohistochemical study of 72 cases with comparison to gross cystic disease
fluid protein 15.
AB - BACKGROUND: GATA-binding protein 3 (GATA3) has been identified as a sensitive
marker for breast carcinoma but its sensitivity in primary genital extramammary
Paget diseases (EMPDs) has not been well studied. METHODS: Here we investigated
immunohistochemical expression of GATA3 in 72 primary genital EMPDs (35 from
female, 37 from male; 45 with intraepithelial disease only, 26 with both
intraepithelial disease and invasive adenocarcinoma including 14 also metastasis,
1 with metastatic adenocarcinoma only for study). We also compared GATA3 to gross
cystic disease fluid protein 15 (GCDFP15) for their sensitivity. RESULTS:
Positive GATA3 staining was seen in all 71 (100%) intraepithelial diseases, 25/26
(96%; female 10/10, male 15/16) invasive adenocarcinomas and 14/15 (93%; female
3/3, male 11/12) metastatic adenocarcinomas, respectively. Positive GCDFP15
staining was seen in 46/71 (65%; female 28/34 or 82%, male 18/37 or 49%)
intraepithelial diseases, 20/26 (77%; female 9/10, male 11/16) invasive
adenocarcinomas, and 12/15 (80%; female 2/3, male 10/12) metastatic
adenocarcinomas, respectively (GATA3 versus GCDFP15: p < 0.01 for both
intraepithelial disease and invasive adenocarcinoma, p = 0.28 for metastatic
adenocarcinoma). In positive-stained cases, GATA3 stained more tumor cells than
GCDFP15 (79% versus 25% for intraepithelial disease, 71% vs 34% for invasive
adenocarcinoma, 73% vs 50% for metastatic adenocarcinoma, p < 0.01 for all 3
components). CONCLUSIONS: Our findings indicate that GATA3 is a very sensitive
marker for primary genital EMPDs and is more sensitive than GCDFP15.
PMID- 28693611
TI - Dual function of the nuclear export signal of the Borna disease virus
nucleoprotein in nuclear export activity and binding to viral phosphoprotein.
AB - BACKGROUND: Borna disease virus (BoDV), which has a negative-sense, single
stranded RNA genome, causes persistent infection in the cell nucleus. The nuclear
export signal (NES) of the viral nucleoprotein (N) consisting of leucine at
positions 128 and 131 and isoleucine at positions 133 and 136 overlaps with one
of two predicted binding sites for the viral phosphoprotein (P). A previous study
demonstrated that higher expression of BoDV-P inhibits nuclear export of N;
however, the function of N NES in the interaction with P remains unclear. We
examined the subcellular localization, viral polymerase activity, and P-binding
ability of BoDV-N NES mutants. We also characterized a recombinant BoDV (rBoDV)
harboring an NES mutation of N. RESULTS: BoDV-N with four alanine-substitutions
in the leucine and isoleucine residues of the NES impaired its cytoplasmic
localization and abolished polymerase activity and P-binding ability. Although an
alanine-substitution at position 131 markedly enhanced viral polymerase activity
as determined by a minigenome assay, rBoDV harboring this mutation showed
expression of viral RNAs and proteins relative to that of wild-type rBoDV.
CONCLUSIONS: Our results demonstrate that BoDV-N NES has a dual function in BoDV
replication, i.e., nuclear export of N and an interaction with P, affecting viral
polymerase activity in the nucleus.
PMID- 28693612
TI - Genome-resolved metaproteomic characterization of preterm infant gut microbiota
development reveals species-specific metabolic shifts and variabilities during
early life.
AB - BACKGROUND: Establishment of the human gut microbiota begins at birth. This early
life microbiota development can impact host physiology during infancy and even
across an entire life span. However, the functional stability and population
structure of the gut microbiota during initial colonization remain poorly
understood. Metaproteomics is an emerging technology for the large-scale
characterization of metabolic functions in complex microbial communities (gut
microbiota). RESULTS: We applied a metagenome-informed metaproteomic approach to
study the temporal and inter-individual differences of metabolic functions during
microbial colonization of preterm human infants' gut. By analyzing 30 individual
fecal samples, we identified up to 12,568 protein groups for each of four
infants, including both human and microbial proteins. With genome-resolved
matched metagenomics, proteins were confidently identified at the species/strain
level. The maximum percentage of the proteome detected for the abundant organisms
was ~45%. A time-dependent increase in the relative abundance of microbial versus
human proteins suggested increasing microbial colonization during the first few
weeks of early life. We observed remarkable variations and temporal shifts in the
relative protein abundances of each organism in these preterm gut communities.
Given the dissimilarity of the communities, only 81 microbial EggNOG orthologous
groups and 57 human proteins were observed across all samples. These conserved
microbial proteins were involved in carbohydrate, energy, amino acid and
nucleotide metabolism while conserved human proteins were related to immune
response and mucosal maturation. We identified seven proteome clusters for the
communities and showed infant gut proteome profiles were unstable across time and
not individual-specific. Applying a gut-specific metabolic module (GMM) analysis,
we found that gut communities varied primarily in the contribution of nutrient
(carbohydrates, lipids, and amino acids) utilization and short-chain fatty acid
production. CONCLUSIONS: Overall, this study reports species-specific proteome
profiles and metabolic functions of human gut microbiota during early
colonization. In particular, our work contributes to reveal microbiota-associated
shifts and variations in the metabolism of three major nutrient sources and short
chain fatty acid during colonization of preterm infant gut.
PMID- 28693613
TI - Cascading training the trainers in ophthalmology across Eastern, Central and
Southern Africa.
AB - BACKGROUND: The Royal College of Ophthalmologists (RCOphth) and the College of
Ophthalmology of Eastern Central and Southern Africa (COECSA) are collaborating
to cascade a Training the Trainers (TTT) Programme across the COECSA Region.
Within the VISION 2020 Links Programme, it aims to develop a skilled motivated
workforce who can deliver high quality eye care. It will train a lead, faculty
member and facilitator in 8 countries, who can cascade the programme to local
trainers. METHODS: In phase 1 (2013/14) two 3-day courses were run for 16/17
selected delegates, by 3 UK Faculty. In phase 2 (2015/16) 1 UK Faculty Member ran
3 shorter courses, associated with COECSA events (Congress and Examination). A
COECSA Lead was appointed after the first course, and selected delegates were
promoted as Facilitators then Faculty Members on successive courses. They were
given appropriate materials, preparation, training and mentoring. RESULTS: In 4
years the programme has trained 87 delegates, including 1 COECSA Lead, 4 Faculty
Members and 7 Facilitators. Delegate feedback on the course was very good and
Faculty were impressed with the progress made by delegates. A questionnaire
completed by delegates after 6-42 months demonstrated how successfully they were
implementing new skills in teaching and supervision. The impact was assessed
using the number of eye-care workers that delegates had trained, and the number
of patients seen by those workers each year. The figures suggested that
approaching 1 million patients per year were treated by eye-care workers who had
benefited from training delivered by those who had been on the courses.
Development of the Programme in Africa initially followed the UK model, but the
need to address more extensive challenges overseas, stimulated new ideas for the
UK courses. CONCLUSIONS: The Programme has developed a pyramid of trainers
capable of cascading knowledge, skills and teaching in training with RCOphth
support. The third phase will extend the number of facilitators and faculty,
develop on-line preparatory and teaching materials, and design training processes
and tools for its assessment. The final phase will see local cascade of the TTT
Programme in all 8 countries, and sustainability as UK support is withdrawn.
PMID- 28693614
TI - "I cry every day and night, I have my son tied in chains": physical restraint of
people with schizophrenia in community settings in Ethiopia.
AB - BACKGROUND: A primary rationale for scaling up mental health services in low and
middle-income countries is to address human rights violations, including physical
restraint in community settings. The voices of those with intimate experiences of
restraint, in particular people with mental illness and their families, are
rarely heard. The aim of this study was to understand the experiences of, and
reasons for, restraint of people with schizophrenia in community settings in
rural Ethiopia in order to develop constructive and scalable interventions.
METHODS: A qualitative study was conducted, involving 15 in-depth interviews and
5 focus group discussions (n = 35) with a purposive sample of people with
schizophrenia, their caregivers, community leaders and primary and community
health workers in rural Ethiopia. Thematic analysis was used. RESULTS: Most of
the participants with schizophrenia and their caregivers had personal experience
of the practice of restraint. The main explanations given for restraint were to
protect the individual or the community, and to facilitate transportation to
health facilities. These reasons were underpinned by a lack of care options, and
the consequent heavy family burden and a sense of powerlessness amongst
caregivers. Whilst there was pervasive stigma towards people with schizophrenia,
lack of awareness about mental illness was not a primary reason for restraint.
All types of participants cited increasing access to treatment as the most
effective way to reduce the incidence of restraint. CONCLUSION: Restraint in
community settings in rural Ethiopia entails the violation of various human
rights, but the underlying human rights issue is one of lack of access to
treatment. The scale up of accessible and affordable mental health care may go
some way to address the issue of restraint. TRIAL REGISTRATION:
Clinicaltrials.gov NCT02160249 Registered 3rd June 2014.
PMID- 28693615
TI - Genome analysis of Clostridium perfringens isolates from healthy and necrotic
enteritis infected chickens and turkeys.
AB - OBJECTIVE: Clostridium perfringens causes gastrointestinal diseases in both
humans and domestic animals. Type A strains expressing the NetB toxin are the
main cause of necrotic enteritis (NE) in chickens, which has remarkable impact on
animal welfare and production economy in the international poultry industry.
Three pathogenicity loci NELoc-1, -2 and -3 and a collagen adhesion gene cnaA
have been found to be associated with NE in chickens, whereas the presence of
these has not been investigated in diseased turkeys. The purpose was to
investigate the virulence associated genome content and the genetic relationship
among 30 C. perfringens isolates from both healthy and NE infected chickens and
turkeys, applying whole-genome sequencing. RESULTS: NELoc-1, -3, netB and cnaA
were significantly associated with NE isolates from chickens, whereas only NELoc
2 was commonly observed in both diseased turkeys and chickens. A putative
collagen adhesion gene that encodes a von Willebrand Factor (vWF) domain was
identified in all diseased turkeys and designated as cnaD. The phylogenetic
analysis based on single nucleotide polymorphisms showed that the isolates
generally were not closely related. These results indicate that virulence factors
and pathogenicity loci associated with NE in chickens are not important to the
same extent in diseased turkeys except for NELoc-2. A putative collagen adhesion
gene which potentially could be of importance in regard to the NE pathogenesis in
turkeys was identified and need to be further investigated. Thus, the
pathogenesis of NE in turkeys appears to be different from that of broiler
chickens.
PMID- 28693616
TI - Microbial pathogens associated with acute childhood diarrhoea in Kumasi, Ghana.
AB - BACKGROUND: Diarrhoeal diseases are among the most frequent causes of morbidity
and mortality in children worldwide, especially in sub-Saharan Africa. This case
control study was conducted to investigate the bacterial, viral and parasitic
pathogens associated with acute diarrhoea among children attending three health
facilities in Kumasi, Ghana. METHODS: Stool specimens were collected from 240
children under 5 years of age visiting hospitals in Kumasi, Ghana due to acute
diarrhoea and from 107 healthy controls of similar age. Both intestinal and
malaria parasites were diagnosed by microscopy whereas rota- and adenoviruses
were identified by stool antigen immunochromatograhic testing. Bacterial
enteropathogens were detected by conventional culture techniques. RESULTS: Of all
subjects, 23 (6.6%) were positive for malaria parasitaemia, 139 (40.1%) had at
least one bacterial agent in their stool and 25 (7.2%) had ova or parasites.
Subjects infected with malaria had the highest odds of having diarrhoea [12.0
(95% CI 1.56, 92.35)] followed by those with rotaviruses [4.4 (95% CI 2.05,
9.47)] and bacterial infection [4.99 (95% CI 1.45, 17.17)]. CONCLUSION: In
conclusion, this study was unique as it looked at the three groups of pathogens
(parasites, viruses and bacteria) that cause acute diarrhoea in children in the
Kumasi metropolis of Ghana. This study has shown for the first time since 2004
that malaria parasitaemia, rotavirus and bacterial infections still remain common
pathogens associated with acute childhood diarrhoea in the Kumasi metropolis of
Ghana.
PMID- 28693617
TI - Socio-demographic determinants of skilled birth attendant at delivery in rural
southern Ghana.
AB - BACKGROUND: Maternal mortality is the subject of the United Nations' fifth
Millennium Development Goal, which is to reduce the maternal mortality ratio by
three quarters from 1990 to 2015. The giant strides made by western countries in
dropping of their maternal mortality ratio were due to the recognition given to
skilled attendants at delivery. In Ghana, nine in ten mothers receive antenatal
care from a health professional whereas only 59 and 68% of deliveries are
assisted by skilled personnel in 2008 and 2010 respectively. This study therefore
examines the determinants of skilled birth attendant at delivery in rural
southern Ghana. METHODS: This study comprises of 1874 women of reproductive age
who had given birth 2 years prior to the study whose information were extracted
from the Dodowa Health and Demographic Surveillance System. The univariable and
multivariable associations between exposure variables (risk factors) and skilled
birth attendant at delivery were explored using logistic regression. RESULTS: Out
of a total of 1874 study participants, 98.29% of them receive antenatal care
services during pregnancy and only 68.89% were assisted by skilled person at
their last delivery prior to the survey. The result shows a remarkable influence
of maternal age, level of education, parity, socioeconomic status and antenatal
care attendance on skilled attendants at delivery. CONCLUSION: Although 69% of
women in the study had skilled birth attendants at delivery, women from poorest
households, higher parity, uneducated, and not attending antenatal care and
younger women were more likely to deliver without a skilled birth attendants at
delivery. Future intervention in the study area to bridge the gap between the
poor and least poor women, improve maternal health and promote the use of skilled
birth at delivery is recommended.
PMID- 28693618
TI - Simple and fast quantification of DNA damage by real-time PCR, and its
application to nuclear and mitochondrial DNA from multiple tissues of aging
zebrafish.
AB - We describe a real-time (rt) PCR-based method of quantifying DNA damage, adapted
from the long-run rtPCR method of DNA damage quantification (LORD-Q) developed by
Lehle et al. (Nucleic Acids Res 42(6):e41, 2014). We show that semi-long run
rtPCR, which generates amplicons half the length of those generated in LORD-Q,
provides equivalent sensitivity for detecting low lesion frequencies, and better
sensitivity for detecting high frequencies. The smaller amplicon size greatly
facilitates PCR optimization and allows greater flexibility in the use of
detection dyes, and a modified data analysis method simplifies the calculation of
lesion frequency. The method was used to measure DNA damage in the nuclear and
mitochondrial genomes of different tissues in zebrafish of different ages. We
find that nuclear DNA damage generally increases with age, and that the amount of
mitochondrial DNA damage varies substantially between tissues, increasing with
age in liver and brain but not in heart or skeletal muscle, the latter having the
highest levels of damage irrespective of age.
PMID- 28693619
TI - Successful pregnancy after mucinous cystic neoplasm with invasive carcinoma of
the pancreas in a patient with polycystic ovarian syndrome: a case report.
AB - BACKGROUND: The incidence of invasive cancer within a mucinous cystic neoplasm of
the pancreas varies between 6 and 36%. Polycystic ovarian syndrome is a disorder
characterized by hyperandrogenism and anovulatory infertility. One surgical
treatment that can restore endocrine balance and ovulation in polycystic ovarian
syndrome is partial ovarian destruction. Successful pregnancies following
preconception pancreaticoduodenectomies (Whipple procedures) and chemoradiation
to treat pancreatic neoplasms have been reported rarely but none were diagnosed
with pre-cancer polycystic ovarian syndrome-associated infertility. Gemcitabine
is an antimetabolite drug used for the treatment of pancreatic cancer that can
have profound detrimental effects on oogenesis and ovarian function. Whether the
ovarian destructive property of gemcitabine could act as a method to restore
ovulation potential in polycystic ovarian syndrome is unknown. CASE PRESENTATION:
A 40-year-old white American woman with a history of pancreatic cancer treatment
with a Whipple procedure and chemoradiation with gemcitabine had a successful
pregnancy after years of pre-cancerous anovulatory infertility and polycystic
ovarian syndrome. She received no fertility agents and delivered full term via a
spontaneous vaginal delivery with no pregnancy complications. CONCLUSION:
Gemcitabine treatment for pancreatic cancer may result in resumption of ovulation
in women with polycystic ovarian syndrome and these women should be counseled
accordingly.
PMID- 28693620
TI - Development of an in silico method for the identification of subcomplexes
involved in the biogenesis of multiprotein complexes in Saccharomyces cerevisiae.
AB - BACKGROUND: Large sets of protein-protein interaction data coming either from
biological experiments or predictive methods are available and can be combined to
construct networks from which information about various cell processes can be
extracted. We have developed an in silico approach based on these information to
model the biogenesis of multiprotein complexes in the yeast Saccharomyces
cerevisiae. RESULTS: Firstly, we have built three protein interaction networks by
collecting the protein-protein interactions, which involved the subunits of three
complexes, from different databases. The protein-protein interactions come from
different kinds of biological experiments or are predicted. We have chosen the
elongator and the mediator head complexes that are soluble and exhibit an
architecture with subcomplexes that could be functional modules, and the
mitochondrial bc 1 complex, which is an integral membrane complex and for which a
late assembly subcomplex has been described. Secondly, by applying a clustering
strategy to these networks, we were able to identify subcomplexes involved in the
biogenesis of the complexes as well as the proteins interacting with each
subcomplex. Thirdly, in order to validate our in silico results for the
cytochrome bc1 complex we have analysed the physical interactions existing
between three subunits by performing immunoprecipitation experiments in several
genetic context. CONCLUSIONS: For the two soluble complexes (the elongator and
mediator head), our model shows a strong clustering of subunits that belong to a
known subcomplex or module. For the membrane bc 1 complex, our approach has
suggested new interactions between subunits in the early steps of the assembly
pathway that were experimentally confirmed. Scripts can be downloaded from the
site: http://bim.igmors.u-psud.fr/isips .
PMID- 28693621
TI - Increasing utilisation of skilled facility-based maternal healthcare services in
rural Zambia: the role of safe motherhood action groups.
AB - BACKGROUND: Community-centred health interventions, such as Safe Motherhood
Action groups (SMAGs), have potential to lead to desired health behavioural
change and favourable health outcomes. SMAGs are community-based volunteer groups
that aim to reduce critical delays that occur at household level with regard to
decision-making about seeking life-saving maternal care at health facilities. The
aim of this study was to explore perspectives, roles, achievements and challenges
of the SMAG programme in Kalomo, Zambia. METHODS: In-depth interviews (IDIs) were
conducted in 7 health centres in Kalomo district between 1st April and 20th May,
2015 with 46 respondents comprising 22 SMAG members, 5 headmen, 10 mothers, 3
husbands, 5 nurses, and 1 district maternal and child health coordinator.
Perspectives on the selection, training, roles, achievements and challenges of
the SMAG programme were explored. RESULTS: Respondents were aware of the
presence, selection, training and roles of the SMAG members and had a positive
attitude towards the programme. They believed that the SMAG programme led to an
increase in women's risk perception about pregnancy and childbirth-related
complications. Further, participants believed that the programme resulted in
increased utilisation of facility-based antenatal, delivery and postnatal care,
and improvement in maternal and newborn health outcomes. However, various
challenges affected implementation of the SMAG programme. Among these were
insufficient material and financial support to the programme, lack of refresher
training for SMAG members, poor quality of care in health care facilities due to
a lack of maternity waiting homes, low staffing levels in health facilities, the
poor state and small size of the labour wards, and lack of equipment to handle
obstetric emergencies. CONCLUSION: The SMAG programme has potential to be an
important community intervention for increasing utilisation of facility-based
skilled care and improving maternal and newborn health outcomes.
PMID- 28693623
TI - Epidemiologic Review of Veterans Health Administration Patients with Isolation of
Nontuberculous Mycobacteria after Cardiopulmonary Bypass Procedures.
AB - We evaluated the isolation of postoperative nontuberculous mycobacteria (NTM)
associated with heater-cooler devices (HCDs) used during cardiopulmonary bypass
(CPB) surgery in the Veterans Health Administration from January 1, 2010, to
December 31, 2016. In more than 38,000 CPB procedures, NTM was isolated in 111
patients; 1 Mycobacterium chimaera mediastinitis case and 1 respiratory isolate
were found. Infect Control Hosp Epidemiol 2017;38:1103-1106.
PMID- 28693622
TI - Prevention and treatment of long-term social disability amongst young people with
emerging severe mental illness with social recovery therapy (The PRODIGY Trial):
study protocol for a randomised controlled trial.
AB - BACKGROUND: Young people who have social disability associated with severe and
complex mental health problems are an important group in need of early
intervention. Their problems often date back to childhood and become chronic at
an early age. Without intervention, the long-term prognosis is often poor and the
economic costs very large. There is a major gap in the provision of evidence
based interventions for this group, and therefore new approaches to detection and
intervention are needed. This trial provides a definitive evaluation of a new
approach to early intervention with young people with social disability and
severe and complex mental health problems using social recovery therapy (SRT)
over a period of 9 months to improve mental health and social recovery outcomes.
METHODS: This is a pragmatic, multi-centre, single blind, superiority randomised
controlled trial. It is conducted in three sites in the UK: Sussex, Manchester
and East Anglia. Participants are aged 16 to 25 and have both persistent and
severe social disability (defined as engaged in less than 30 hours per week of
structured activity) and severe and complex mental health problems. The target
sample size is 270 participants, providing 135 participants in each trial arm.
Participants are randomised 1:1 using a web-based randomisation system and
allocated to either SRT plus optimised treatment as usual (enhanced standard
care) or enhanced standard care alone. The primary outcome is time use, namely
hours spent in structured activity per week at 15 months post-randomisation.
Secondary outcomes assess typical mental health problems of the group, including
subthreshold psychotic symptoms, negative symptoms, depression and anxiety. Time
use, secondary outcomes and health economic measures are assessed at 9, 15 and 24
months post-randomisation. DISCUSSION: This definitive trial will be the first to
evaluate a novel psychological treatment for social disability and mental health
problems in young people presenting with social disability and severe and complex
non-psychotic mental health problems. The results will have important
implications for policy and practice in the detection and early intervention for
this group in mental health services. TRIAL REGISTRATION: Trial Registry:
International Standard Randomised Controlled Trial Number (ISRCTN) Registry.
TRIAL REGISTRATION NUMBER: ISRCTN47998710 (registered 29/11/2012).
PMID- 28693624
TI - Modeling adult emergence and fecundity of factitious hosts under different food
sources supports massive egg production management.
AB - Ephestia kuehniella (Lepidoptera, Pyralidae) and Sitotroga cerealella
(Lepidoptera, Gelechiidae) are important factitious hosts used for production of
biological control agents. Their differences in terms of biology and behavior
require adjustments in their mass production, particularly when using corn or
barley as food in grain or in bran. We modeled adult emergence, oviposition
period and egg production along time after emergence, as a function of the food
source. Significant differences between hosts or food type were found for these
variables and for adult weight but not for sex ratio. Our results confirm the
possibility of mass production of these hosts using corn or barley as food
source. Integrating adult emergence patterns and age specific fecundity patterns
into a single model, it is clear that rearing E. kuehniella on barley would
result in the highest egg output in much shorter time than E. kuehniella on corn
or S. cerealella on barley.
PMID- 28693625
TI - A Role for Antimicrobial Stewardship in Clinical Sepsis Pathways: a Prospective
Interventional Study.
AB - OBJECTIVE To evaluate the impact of early infectious diseases (ID) antimicrobial
stewardship (AMS) intervention on inpatient sepsis antibiotic management. DESIGN
Interventional, nonrandomized, controlled study. SETTING Tertiary-care referral
hospital, Sydney, Australia. PATIENTS Consecutive, adult, non-intensive care unit
(non-ICU) inpatients triggering an institutional clinical sepsis pathway from May
to August 2015. INTERVENTION All patients reviewed by an ID Fellow within 24
hours of sepsis pathway trigger underwent case review and clinic file
documentation of recommendations. Those not reviewed by an ID Fellow were
considered controls and received standard sepsis pathway care. The primary
outcome was antibiotic appropriateness 48 hours after sepsis trigger. RESULTS In
total, 164 patients triggered the sepsis pathway: 6 patients were excluded
(previous sepsis trigger); 158 patients were eligible; 106 had ID intervention;
and 52 were control cases. Of these 158 patients, 91 (58%) had sepsis, and 15 of
these 158 (9.5%) had severe sepsis. Initial antibiotic appropriateness,
assessable in 152 of 158 patients, was appropriate in 80 (53%) of these 152
patients and inappropriate in 72 (47%) of these patients. In the intervention
arm, 93% of ID Fellow recommendations were followed or partially followed,
including 53% of cases in which antibiotics were de-escalated. ID Fellow
intervention improved antibiotic appropriateness at 48 hours by 24% (adjusted
risk ratio, 1.24; 95% confidence interval, 1.04-1.47; P=.035). The
appropriateness agreement among 3 blinded ID staff opinions was 95%. Differences
in intervention and control group mortality (13% vs 17%) and median length of
stay (13 vs 17.5 days) were not statistically significant. CONCLUSION Sepsis
overdiagnosis and delayed antibiotic optimization may reduce sepsis pathway
effectiveness. Early ID AMS improved antibiotic management of non-ICU inpatients
with suspected sepsis, predominantly by de-escalation. Further studies are needed
to evaluate clinical outcomes. Infect Control Hosp Epidemiol 2017;38:1032-1038.
PMID- 28693626
TI - Surgical Site Infections After Liver Transplantation: Prospective Surveillance
and Evaluation of 250 Transplant Recipients in Canada.
AB - OBJECTIVE To evaluate the incidence of surgical-site infections (SSIs) in a
cohort of liver transplant recipients and to assess risk factors predisposing
patients to these infections. DESIGN Prospective observational cohort study.
SETTING Single transplant center in Canada. PATIENTS Patients who underwent liver
transplantation between February 2011 and August 2014. METHODS Multivariate
logistic regression was used to identify independent risk factors for SSIs in
liver transplant patients. RESULTS We enrolled 250 liver transplant recipients.
The recipients' median age at the time of transplantation was 56 years (range, 19
70 years), and 166 patients (66.4%) were male. Moreover, 47 SSIs were documented
in 43 patients (17.2%). Organ-space, superficial, and deep SSIs were noted in 29,
7, and 3 patients, respectively. In addition, 2 patients developed superficial
and organ-space SSIs, and another 2 patients were found to have deep as well as
organ-space infections. In total, we identified 33 organ-space SSIs (70.2%), 9
superficial SSIs (19.1%), and 5 deep SSIs (10.6%). Factors predictive of SSIs by
multivariate analysis were duct-to-duct anastomosis (odds ratio [OR], 3.88; 95%
CI, 1.85-8.13; P<.001) and dialysis (OR, 3.57; 95% CI, 1.02-12.50; P=.046). Of
the 66 organisms isolated in both deep and organ-space SSIs, 55 (83%) were
resistant to cefazolin. CONCLUSIONS Organ-space SSIs are a common complication
after liver transplantation. Duct-to-duct anastomosis and dialysis were
independent risk factors associated with SSIs. Appropriate perioperative
prophylaxis targeting patients with duct-to-duct anastomosis and dialysis while
simultaneously providing optimum coverage for the potential pathogens causing
SSIs is warranted. Infect Control Hosp Epidemiol 2017;38:1084-1090.
PMID- 28693627
TI - Morphofunctional evaluation of the testis, duration of spermatogenesis and
spermatogenic efficiency in the Japanese fancy mouse (Mus musculus molossinus).
AB - Japanese fancy mouse, mini mouse or pet mouse are common names used to refer to
strains of mice that present with different colour varieties and coat types.
Although many genetic studies that involve spotting phenotype based on the coat
have been performed in these mice, there are no reports of quantitative data in
the literature regarding testis structure and spermatogenic efficiency. Hence, in
this study we researched testis function and spermatogenesis in the adult
Japanese fancy mouse. The following values of 68 +/- 6 mg and 0.94 +/- 0.1% were
obtained as mean testis weight and gonadosomatic index, respectively. In
comparison with other investigated mice strains, the fancy mouse Leydig cell
individual size was much smaller, resulting in higher numbers of these cells per
gram of testis. As found for laboratory mice strains, as a result of the
development of the acrosomic system, 12 stages of the seminiferous epithelium
cycle have been described in this study. The combined frequencies of pre-meiotic
and post-meiotic stages were respectively 24% and 64% and very similar to the
laboratory mice. The more differentiated germ cell types marked at 1 h or 9 days
after tritiated thymidine administration were preleptotene/leptotene and
pachytene spermatocytes at the same stage (VIII). The mean duration of one
spermatogenic cycle was 8.8 +/- 0.01 days and the total length of spermatogenesis
lasted 37.8 +/- 0.01 days (4.5 cycles). A high number of germ cell apoptosis was
evident during meiosis, resulting in lower Sertoli cell and spermatogenic
efficiencies, when compared with laboratory mice strains.
PMID- 28693628
TI - Optimising the use of otowicks in otitis externa.
AB - OBJECTIVE: Otowicks are used to treat otitis externa with significant ear canal
oedema. This study investigates how well drops penetrate through to reach the
deep canal and whether it is safe to leave otowicks in the canal for more than 2
days. METHODS: Sterile otowicks were inserted into mock ear canals and vertically
over pseudomonas-seeded agar plates whilst gentamicin or ciprofloxacin drops were
administered. The time taken for drops to penetrate through the otowick was
recorded. Separately, pseudomonas-seeded otowicks were treated with saline or
antibacterial drops. The penetrating drops were observed for bacterial growth on
sterile agar. RESULTS: It took six drops before penetration occurred for both
antibiotics. When sterile saline drops were applied to bacterially contaminated
otowicks, the penetrating drops displayed bacterial growth on agar, indicating
that pseudomonas penetrated through the otowick. However, when antibiotic drops
were applied, penetrating drops showed no bacterial growth on the corresponding
agar plate. CONCLUSION: Bacteria can penetrate otowicks but this is prevented by
continuous application of antibacterial ear drops. Ear wicks need priming with
six drops before starting a regimen, so that the initial dose is fully absorbed.
PMID- 28693629
TI - Resveratrol has dose-dependent effects on DNA fragmentation and mitochondrial
activity of ovine secondary follicles cultured in vitro.
AB - The worldwide consumption of red wine, nuts and grapes has resulted in increased
human exposure to resveratrol, which could affect reproductive function. However,
the effect of resveratrol on in vitro culture of early-stage ovarian follicles
has never been investigated. The aims of the present study were to evaluate the
effect of resveratrol on sheep secondary follicle morphology, growth, DNA
fragmentation, intracellular levels of glutathione (GSH) and active mitochondria.
Secondary follicles were isolated from the ovaries and cultured for 18 days in
supplemented alpha-MEM+ (control medium) or in control medium containing
resveratrol (2, 10 or 30 uM). The parameters analyzed were morphology, antrum
formation, follicle diameter, DNA fragmentation, GSH levels and mitochondrial
activity. After 18 days, all resveratrol groups significantly decreased the
percentages of morphologically normal follicles compared with the control group
(alpha-MEM+). Antrum formation was higher in both alpha-MEM+ and 2 uM resveratrol
groups than in the 10 uM resveratrol group. In addition, 30 uM resveratrol
increased the percentage of oocytes with DNA damage compared with the control.
Oocytes from follicles treated with 10 or 30 uM resveratrol significantly
decreased intracellular GSH levels compared with the 2 uM resveratrol group.
Moreover, follicles in alpha-MEM+ (control) showed more active mitochondria than
those in 10 or 30 uM resveratrol. In conclusion, ovine isolated secondary
follicles are able to grow to the antral stage after in vitro culture in medium
containing 2 uM resveratrol, maintaining the same rates of DNA damage, GSH levels
and mitochondrial function as the control medium. However, the addition of 30 uM
resveratrol increased DNA fragmentation and oxidative stress through decreasing
mitochondrial activity.
PMID- 28693630
TI - Developmental competence of Dromedary camel (Camelus dromedarius) oocytes
selected using brilliant cresyl blue staining.
AB - The objectives of the present studies were to investigate the developmental
capacity of dromedary camel oocytes selected by brilliant cresyl blue (BCB)
staining and to investigate the expression of select transcripts in germinal
vesicle (GV) stage oocytes. These transcripts included BMP15 and GDF9 as
important transcripts for folliculogenesis and oocyte development, Zar1 and Mater
as maternal transcripts required for embryonic development, Cyclin B1 and CDK1 as
cell cycle regulators and Oct4 and STAT3 as transcription factors. Dromedary
camel oocytes were retrieved from ovaries collected at a local slaughterhouse.
After exposure to BCB staining, cumulus-oocyte complexes (COCs) from BCB+, BCB-
and control (selected based on morphological criteria) groups were subjected to
in vitro maturation, in vitro fertilization and in vitro culture. For gene
expression studies, after BCB staining cumulus cells were stripped off and the
completely denuded GV stage oocytes were used for RT-PCR analysis of selected
transcripts. BCB+ oocytes showed higher maturation, and fertilization rates
compared with BCB- and control groups. Indices of early embryonic development,
namely, cleavage at 48 hours post insemination (hpi), and development to morula
at day 5 and day 7 blastocyst rates were also significantly higher in the BCB+
group. RT-PCR revealed a higher expression of BMP15, GDF9, Zar1, Mater, Cyclin
B1, CDK1, OCT4 and STAT3 in good quality oocytes that stained positively for BCB
(BCB+). Collectively, results provide novel information about the use of BCB
screening for selecting good quality oocytes to improve in vitro embryo
production in the dromedary camel.
PMID- 28693631
TI - Palliative care education in Latin America: A systematic review of training
programs for healthcare professionals.
AB - OBJECTIVE: The integration of palliative care (PC) education into medical and
nursing curricula has been identified as an international priority. PC education
has undergone significant development in Latin America, but gaps in the
integration of PC courses into undergraduate and postgraduate curricula remain.
The aim of our review was to systematically examine the delivery of PC education
in Latin America in order to explore the content and method of delivery of
current PC programs, identify gaps in the availability of education
opportunities, and document common barriers encountered in the course of their
implementation. METHOD: We carried out a systematic review of peer-reviewed
academic articles and grey literature. Peer-reviewed articles were obtained from
the following databases: CINAHL Plus, Embase, the Web of Science, and Medline.
Grey literature was obtained from the following directories: the International
Association for Hospice and Palliative Care's Global Directory of Education in
Palliative Care, the Worldwide Hospice Palliative Care Alliance's lists of
palliative care resources, the Latin American Association for Palliative Care's
training resources, and the Latin American Atlas of Palliative Care. The
inclusion criteria were that the work: (1) focused on describing PC courses; (2)
was aimed at healthcare professionals; and (3) was implemented in Latin America.
The PRISMA checklist was employed to guide the reporting of methods and findings.
RESULTS: We found 36 programs that were delivered in 8 countries. Most of the
programs were composed of interdisciplinary teams, taught at a postgraduate
level, focused on pain and symptom management, and utilized classroom-based
methods. The tools for evaluating the courses were rarely reported. The main
barriers during implementation included: a lack of recognition of the importance
of PC education, a lack of funding, and the unavailability of trained teaching
staff. SIGNIFICANCE OF RESULTS: Considerable work needs to be done to improve the
delivery of PC education programs in Latin American countries. Practice-based
methods and exposure to clinical settings should be integrated into ongoing
courses to facilitate learning. A regional platform needs to be created to share
experiences of successful training programs and foster the development of PC
education throughout Latin America.
PMID- 28693632
TI - Longitudinal study of parasite-induced mortality of a long-lived host: the
importance of exposure to non-parasitic stressors.
AB - Hosts face mortality from parasitic and environmental stressors, but interactions
of parasitism with other stressors are not well understood, particularly for long
lived hosts. We monitored survival of flour beetles (Tribolium confusum) in a
longitudinal design incorporating cestode (Hymenolepis diminuta) infection,
starvation and exposure to the pesticide diatomaceous earth (DE). We found that
cestode cysticercoids exhibit increasing morphological damage and decreasing
ability to excyst over time, but were never eliminated from the host. In the
presence of even mild environmental stressors, host lifespan was reduced
sufficiently that extensive degradation of cysticercoids was never realized.
Median host lifespan was 200 days in the absence of stressors, and 3-197 days
with parasitism, starvation and/or DE. Early survival of parasitized hosts was
higher relative to controls in the presence of intermediate concentrations of DE,
but reduced under all other conditions tested. Parasitism increased host
mortality in the presence of other stressors at times when parasitism alone did
not cause mortality, consistent with an interpretation of synergy. Environmental
stressors modified the parasite numbers needed to reveal intensity-dependent host
mortality, but only rarely masked intensity dependence. The longitudinal approach
produced observations that would have been overlooked or misinterpreted if
survival had only been monitored at a single time point.
PMID- 28693633
TI - Loss of cane and sugar yield resulting from Ceratovacuna lanigera Zehntner damage
in cane-growing regions in China.
AB - Ceratovacuna lanigera Zehntner is a major leaf pest of sugarcane. Widely
distributed, it affects both the yield and quality of sugarcane in China. This
study aimed to assess real yield and sugar yield losses, and the effect of C.
lanigera damage on emergence of newly planted and ratoon cane under current
production levels. Field experiments were carried out from 2014 to 2016 in Yunnan
Province China. At maturity, plants were harvested and weighed to determine
yield, and the effect on sugarcane quality and sucrose content analyzed. Real
yield decreased by average of 46,185 kg hm-2 (range: 37,545-61,845 kg hm-2) in
damaged versus undamaged areas, with an average yield loss rate of 35.9% (28.5
45.7%). Juice yield decreased by an average of 3.01% (2.4-4.13%) and sucrose
content by 6.38% (5.48-8.16%). Juice brix decreased by an average of 7.66 degrees
BX (6.95-9.05 degrees BX) and juice gravity purity by 12.35% (8.43-19.97%). In
contrast, the reducing sugar content increased by an average of 1.21% (1.01
1.3%). Emergence rates of newly planted cane decreased by an average of 26.0%
(24.7-27.3%). The emergence number of ratoon cane decreased by 66,834 hm2 (57,429
76,238 hm-2) and relative emergence loss rates of ratoon cane decreased by an
average of 57.8% (57.6-58.0%). These findings confirm that C. lanigera damage
severely affects sugarcane yield and quality in Yunnan Province. The results will
help the implementation of effective control measures, thereby supporting
sustainable development of the Chinese sugar industry.
PMID- 28693634
TI - Gender and Relationship Status Interaction and Likelihood of Return to Work Post
Retirement.
AB - Population aging is an issue of mounting importance throughout the industrialized
world. Concerns over labour force shortages have led to policies that prolong
working life. Accordingly, present-day workforce participation patterns of older
individuals are extensively varied. This study utilized the 2007 General Social
Survey to examine factors associated with post-retirement paid work, focusing on
the interaction between gender and relationship status, among Canadians aged 50
to 74 who had retired at least once. We find that although being in a
relationship is associated with a higher likelihood of post-retirement work for
men, the opposite is true for women. Our findings suggest that the gendered
association between relationship status and post-retirement work results partly
from the gendered associations between relationship status and one's motivation
for learning and community involvement, career orientation, and sense of
independence. Gendered meanings of relationship status are thus revealed through
analysis of post-retirement work.
PMID- 28693635
TI - Acetylation and methylation profiles of H3K27 in porcine embryos cultured in
vitro.
AB - Methylation and acetylation of histone H3 at lysine 27 (H3K27) regulate chromatin
structure and gene expression during early embryo development. While H3K27
acetylation (H3K27ac) is associated with active gene expression, H3K27
methylation (H3K27me) is linked to transcriptional repression. The aim of this
study was to assess the profile of H3K27 acetylation and methylation (mono-, di-
and trimethyl) during oocyte maturation and early development in vitro of porcine
embryos. Oocytes/embryos were fixed at different developmental stages from
germinal vesicle to day 8 blastocysts and submitted to an immunocytochemistry
protocol to identify the presence and quantify the immunofluorescence intensity
of H3K27ac, H3K27me1, H3K27me2 and H3K27me3. A strong fluorescent signal for
H3K27ac was observed in all developmental stages. H3K27me1 and H3K27me2 were
detected in oocytes, but the fluorescent signal decreased through the cleavage
stages and rose again at the blastocyst stage. H3K27me3 was detected in oocytes,
in only one pronucleus in zygotes, cleaved-stage embryos and blastocysts. The
nuclear fluorescence signal for H3K27me3 increased from the 2-cell stage to 4
cell stage embryos, decreased at the 8-cell and morula stages and increased again
in blastocysts. Different patterns of the H3K27me3 mark were observed at the
blastocyst stage. Our results suggest that changes in the H3K27 methylation
status regulate early porcine embryo development as previously shown in other
species.
PMID- 28693636
TI - Acquisition of Clostridium difficile Colonization and Infection After Transfer
From a Veterans Affairs Hospital to an Affiliated Long-Term Care Facility.
AB - BACKGROUND Clostridium difficile infection (CDI) and asymptomatic carriage of
toxigenic C. difficile are common in long-term care facilities (LTCFs). However,
whether C. difficile is frequently acquired in the LTCF versus during acute-care
admissions remains unknown. OBJECTIVE To test the hypothesis that LTCF residents
often acquire C. difficile colonization and infection in the LTCF DESIGN This 5
month cohort study was conducted to determine the incidence of acquisition of C.
difficile colonization and infection in asymptomatic patients transferred from a
Veterans Affairs hospital to an affiliated LTCF. METHODS Rectal swabs were
cultured for toxigenic C. difficile at the time of transfer to the LTCF and
weekly for up to 6 weeks. We calculated the proportion of LTCF-onset CDI cases
within 1 month of transfer that occurred in residents colonized on admission
versus those with new acquisition in the LTCF. RESULTS Of 110 patients
transferred to the LTCF, 12 (11%) were asymptomatically colonized with toxigenic
C. difficile upon admission, and 4 of these 12 patients (33%) developed CDI
within 1 month, including 3 recurrent and 1 initial CDI episode. Of 82 patients
with negative cultures on transfer and at least 1 follow-up culture, 22 (27%)
acquired toxigenic C. difficile colonization, and 4 developed CDI within 1 month,
including 1 recurrent and 3 initial CDI episodes. CONCLUSION LTCF residents
frequently acquired colonization with toxigenic C. difficile after transfer from
the hospital, and 3 of 4 initial CDI cases with onset within 1 month of transfer
occurred in residents who acquired colonization in the LTCF. Infect Control Hosp
Epidemiol 2017;38:1070-1076.
PMID- 28693637
TI - The effects of ambient temperature and heatwaves on daily Campylobacter cases in
Adelaide, Australia, 1990-2012.
AB - Campylobacter spp. is a commonly reported food-borne disease with major
consequences for morbidity. In conjunction with predicted increases in
temperature, proliferation in the survival of microorganisms in hotter
environments is expected. This is likely to lead, in turn, to an increase in
contamination of food and water and a rise in numbers of cases of infectious
gastroenteritis. This study assessed the relationship of Campylobacter spp. with
temperature and heatwaves, in Adelaide, South Australia. We estimated the effect
of (i) maximum temperature and (ii) heatwaves on daily Campylobacter cases during
the warm seasons (1 October to 31 March) from 1990 to 2012 using Poisson
regression models. There was no evidence of a substantive effect of maximum
temperature per 1 degrees C rise (incidence rate ratio (IRR) 0.995, 95%
confidence interval (95% CI) 0.993-0.997) nor heatwaves (IRR 0.906, 95% CI 0.800
1.026) on Campylobacter cases. In relation to heatwave intensity, which is the
daily maximum temperature during a heatwave, notifications decreased by 19%
within a temperature range of 39-40.9 degrees C (IRR 0.811, 95% CI 0.692-0.952).
We found little evidence of an increase in risk and lack of association between
Campylobacter cases and temperature or heatwaves in the warm seasons. Heatwave
intensity may play a role in that notifications decreased with higher
temperatures. Further examination of the role of behavioural and environmental
factors in an effort to reduce the risk of increased Campylobacter cases is
warranted.
PMID- 28693638
TI - Randomized controlled trial of emergency department initiated smoking cessation
counselling and referral to a community counselling service.
AB - OBJECTIVE: Worldwide, tobacco smoke is still the leading cause of preventable
morbidity and mortality. Many smokers develop chronic smoking-related conditions
that require emergency department (ED) visits. However, best practices for ED
smoking cessation counselling are still unclear. METHODS: A randomized controlled
trial was conducted to determine whether an "ask, advise, and refer" approach
increases 12-month, 30-day quit rates in the stable adult ED smoking population
compared to usual care. Patients in the intervention group were referred to a
community counselling service that offers a quitline, a text-based program, and a
Web-based program. Longitudinal intention-to-treat analyses were performed.
RESULTS: From November 2011 to March 2013, 1,295 patients were enrolled from one
academic tertiary care ED. Six hundred thirty-five were allocated to usual care,
and 660 were allocated to intervention. Follow-up data were available for 70% of
all patients at 12 months. There was no statistically significant difference in
12-month, 30-day quit rates between the two groups. However, there was a trend
towards higher 7-day quit attempts, 7-day quit rates, and 30-day quit rates at 3,
6, and 12 months in the intervention group. CONCLUSION: In this study, there was
a trend towards increased smoking cessation following referral to a community
counselling service. There was no statistically significant difference. However,
if ED smoking cessation efforts were to provide even a small positive effect,
such an intervention may have a significant public health impact given the
extensive reach of emergency physicians.
PMID- 28693639
TI - Review: Factors affecting fouling in conventional pens for slaughter pigs.
AB - This review assesses factors affecting fouling in conventional pens for slaughter
pigs. Fouling of the pen happens when pigs change their excretory behaviour from
occurring in the designated dunging area to the lying area. This can result in a
lower hygiene, bad air quality, extra work for the farmer, disturbance of the
pigs' resting behaviour and an increase in agonistic interactions. A systematic
search was conducted and results narrowed down to 21 articles. Four factors were
found to affect fouling directly: insufficient space allowance, the flooring
design of the pen, the thermal climate and pigs' earlier experience. Further,
these primary factors are affected by secondary factors such as the shape of the
pen, the weight of the pigs and especially the heat balance of the pigs, which is
affected by several tertiary factors including, for example, temperature,
humidity and draught. Results indicate that the most important factor to control
when trying to prevent fouling of a pen is the pen climate. An appropriate
climate may be accomplished through floor cooling in the designated lying area,
sprinklers above the designated dunging area and by ensuring a more optimal
ambient temperature curve that also fits the weight of the pigs in different
stages of the production. All in all, fouling of the pen in conventional
slaughter pigs is a multifactorial problem, but it is important to focus on
increasing the comfortability, and especially the climate, of the designated
lying area.
PMID- 28693640
TI - All-terrain vehicle-related injuries and deaths in Newfoundland and Labrador
between 2003 and 2013: a retrospective trauma registry review.
AB - BACKGROUND: Injury and death involving all-terrain vehicles (ATV) has been
reported in a number of Canadian provinces. The objective of this study is to
describe the frequency, nature, severity, population affected, immediate health
costs, efficacy of related legislation, and helmet use in ATV related injuries
and deaths in Newfoundland and Labrador (NL). METHODS: A retrospective review of
injured or deceased ATV riders of all ages entered in the Newfoundland and
Labrador Trauma Registry from 2003 to 2013 was conducted. Variables studied
included demographics, injury type and severity, use of helmets,
admission/discharge dates, and referring/receiving institution. Data was also
obtained from the Newfoundland and Labrador Center for Health Information (NLCHI)
and included all in-hospital deaths and hospitalizations due to ATVs between 1995
and 2013. RESULTS: There were a total of 298 patients registered in the trauma
registry, resulting in 2759 admission days, nine deaths, and a total estimated
immediate healthcare system cost in excess of $1.6 million. More males (N=253,
84.9%) than females (N=45, 15.1%) were injured in ATV related incidents,
t(20)=7.12, p<.0001. Head and thorax injuries were the most serious. 38.6% of
patients were confirmed to be wearing helmets. Mean injury severity scores are as
follows: head injury (M=11, SD=9.51), thorax (M=10, SD=8.3), abdominal/pelvis
(M=9, SD=7.62), upper extremity (M=9, SD=8.53), other injuries (M=9, SD=10.56)
lower extremity (M=8, SD=8.34), and spine (M=8, SD=6.52). CONCLUSIONS: This study
describes ATV related injuries and deaths in NL. Information from this study may
guide physician practice, public education, and future legislation.
PMID- 28693641
TI - Arterial switch operation in patients with transposition and a left-sided aorta.
AB - OBJECTIVES: Arterial switch operation is the treatment of choice in infants with
transposed arterial trunks. It is technically challenging to perform in patients
having usual atrial arrangement and concordant atrioventricular connections but
having a left-sided aorta. Correction in this setting requires surgical expertise
and precision. Here we review our experience with such patients. METHODS: Between
January, 2002 and October, 2013, the arterial switch operation was performed in
20 patients in the combination emphasised above. Patient records were analysed in
detail for coronary arterial patterns, and for the techniques used for transfer
of the coronary arteries and reconstruction of the great arteries. Outcomes were
recorded in terms of in-hospital survival and left ventricular function at the
most recent follow-up. RESULTS: All patients survived the procedure. Ages ranged
from 3 days to 18 months, with a median of 75 days; the weight of the patients
ranged from 3 to 8.8 kg, with a median of 3.85 kg. The LeCompte manoeuvre was
performed in only nine patients. The mean cardiopulmonary bypass time was 157.5+/
24.9, with a median of 161 minutes, and the mean aortic cross-clamp time was
101.2+/-23.8, with a median of 102 minutes. Subsequently, two patients died: the
first due to a sudden onset of ventricular fibrillation and the second during a
crisis of severe pulmonary hypertension. At the last follow-up, which ranged from
23 to 41 months, with a mean of 38.04+/-2.32 and a median of 38.4 months, all 18
survivors were in NYHA class I, with none requiring cardiac medications and all
having normal bi-ventricular function without residual defects. CONCLUSION: With
appropriate technical modifications, patients with concordant atrioventricular
and discordant ventriculo-arterial connections with a left-sided aorta can
undergo successful anatomical repair.
PMID- 28693642
TI - What's Trending in Infection Control? Scoping and Narrative Reviews.
AB - OBJECTIVE To explore the trends in infection control peer-reviewed journals,
mainstream media, and blogs written by infection control professionals DESIGN
Narrative and scoping reviews METHODS Narrative and scoping reviews were
performed to identify trending infection prevention and control topics from
international journals, national news websites, newspapers, and so-called grey
literature throughout 2015. Data were analyzed using word frequencies, and
results are displayed in word clouds. RESULTS For 2015, our search identified 6
news websites with a total of published 116 articles, 71 articles from selected
newspapers, and 214 publications from infection control websites. In total, 1,059
journal articles were initially identified; 98 articles were anonymous and thus
were excluded, leaving 961 articles in the reviews. The terms 'superbug' and
'antibiotics' were most commonly used in titles of news websites and newspapers,
whereas the terms 'infection' and 'prevention' were most commonly used in
infection control websites or blogs. The word frequency differences among the 4
selected journals reflected their respective specialties. CONCLUSION In infection
prevention and control, the integration of a range of mediums is necessary to
best serve public interests. Whether the aim is advocacy, general health
information dissemination, or warnings of imminent risk, health researchers have
access to multiple forums with different strengths through which to influence
public risk perceptions and responses. Infect Control Hosp Epidemiol 2017;38:1098
1102.
PMID- 28693643
TI - Two new species of Annulotrema (Monogenea: Dactylogyridae) from Hydrocynus
vittatus (Characiformes: Alestidae) in Lake Kariba, Zimbabwe.
AB - Two new and one known species of Annulotrema Paperna & Thurston, 1969 are
reported from the gills of the tigerfish Hydrocynus vittatus Castelnau, 1861,
collected in Lake Kariba, Zimbabwe. The new species, Annulotrema pseudonili n.
sp. and A. bracteatum n. sp., are described and distinguished mainly on the basis
of features of the male copulatory organ (MCO). Annulotrema pseudonili n. sp.
most closely resembles A. nili Paperna, 1973, but differs from it by possessing a
more delicate MCO with a thin-walled base without a fibrous distal part.
Annulotrema bracteatum n. sp. is most similar to Annulotrema ruahae Paperna,
1973, from which it differs by having an MCO composed of a longer copulatory tube
and a leaf-shaped accessory piece enveloping the distal part of the tube. The
presence of Annulotrema pikoides Guegan, Lambert & Birgi, 1988 on H. vittatus in
Zimbabwe represents a new locality record for this parasite.
PMID- 28693644
TI - Gene cloning and difference analysis of vitellogenin in Neoseiulus barkeri
(Hughes).
AB - Neoseiulus barkeri (HUGHES) is the natural enemy of spider mites, whiteflies and
thrips. Screening for chemically-resistant predatory mites is a practical way to
balance the contradiction between the pesticide using and biological control. In
this study, the number of eggs laid by fenpropathrin-susceptible and resistant
strains of N. barkeri was compared. Additionally, we cloned three N. barkeri
vitellogenin (Vg) genes and used quantitative real-time polymerase chain reaction
to quantify Vg expression in susceptible and resistant strains. The total number
of eggs significantly increased in the fenpropathrin-resistant strain. The full
length cDNA cloning of three N. barkeri Vg genes (NbVg1, NbVg2 and NbVg3)
revealed that the open reading frames of NbVg1, NbVg2 and NbVg3 were 5571, 5532
and 4728 bp, encoding 1856, 1843 and 1575 amino acids, respectively. The three N.
barkeri Vg possessed the Vitellogenin-N domain (or lipoprotein N-terminal domain
(LPD_N)), von Willebrand factor type D domain (VWD) and the domain with unknown
function 1943 (DUF1943). The NbVg1 and NbVg2 expression levels were significantly
higher in the resistant strain than in the susceptible strain, while the NbVg3
expression level was lower in the resistant strain. Thus, we speculate that the
increased number of eggs laid by the fenpropathrin-resistant strain of N. barkeri
may be a consequence of changes in Vg gene expression.
PMID- 28693645
TI - Morphometrics and allometry of the larvae of five Characiformes species in the
Paraiba do Sul River Basin.
AB - The aim of this study was to analyse the morphology and allometry of larvae
belonging to five potamodromous species. Five breeding species belonging to the
order Characiformes [Salminus brasiliensis (Cuvier, 1816), Leporinus
steindachneri, Eigenmann, 1907, Prochilodus lineatus (Valenciennes, 1837),
Prochilodus vimboides (Kner,1859) and Brycon insignis, Steindachner, 1877] were
used to obtain larvae samples during the pre-flexing, post-flexing, and juvenile
developmental stages. When we observed the degree-hour (DH) amplitude time
values, we found three developmental groups based on allometry and morphometrics
within the period between the pre-flexing and post-flexing phases. Group 1
consists of the species S. brasiliensis and B. insignis, Group 2 consists of P.
lineatus and P. vimboides, and Group 3 consists of L. steindachneri. Group 1
requires less development time and has more slender larvae. Group 2 has a
moderate development time and larvae with a more rounded shape. Group 3 presents
a greater development time and an intermediate larval morphology. It was possible
to classify the larvae through cross-validated discriminant analyses based on
seven morphometric variables with 90% accuracy in B. insignis, 83% in L.
steindachneri, 91% in P. lineatus, 80% in P. vimboides, and 96% in S.
brasiliensis. These results indicate larval characteristics that can be used for
the taxonomic identification of the icthyoplankton.
PMID- 28693646
TI - Secular Trends in Nosocomial Vancomycin-Resistant Enterococcal Bloodstream
Infections Among United States Veterans Affairs Hospitals, Fiscal Years 2004
through 2014.
PMID- 28693647
TI - Angiostrongylus mackerrasae and A. cantonensis (Nematoda: Metastrongyloidea)
belong to same genetic lineage: evidence from mitochondrial protein-coding genes.
AB - Angiostrongylus mackerrasae is a parasitic nematode of rats found in Australia.
When first reported, it was referred to as A. cantonensis. Recent molecular
studies, including the mitochondrial genome, indicate that it is highly similar
to A. cantonensis. These studies did not include A. malaysiensis, another member
of the A. cantonensis species complex, for comparison. The present study examined
the genetic distance and phylogenetic relationship between the component taxa (A.
cantonensis, A. mackerrasae and A. malaysiensis) of the A. cantonensis species
complex, based on the 12 protein-coding genes (PCGs) of their mitochondrial
genome. Both the nucleotide and amino acid sequences were analysed.
Angiostrongylus mackerrasae and A. cantonensis are members of the same genetic
lineage and both are genetically distinct from A. malaysiensis. The genetic
distance based on concatenated nucleotide sequences of 12 mt-PCGs between A.
mackerrasae and A. cantonensis from Thailand is p = 1.73%, while that between the
Thai and Chinese taxa of A. cantonensis is p = 3.52%; the genetic distance
between A. mackerrasae and A. cantonensis from China is p = 3.70%. The results
indicate that A. mackerrasae and A. cantonensis belong to the same genetic
lineage, and that A. mackerrasae may be conspecific with A. cantonensis. It
remains to be resolved whether A. mackerrasae is conspecific with A. cantonensis
or undergoing incipient speciation.
PMID- 28693648
TI - Optimal doses of EGF and GDNF act as biological response modifiers to improve
porcine oocyte maturation and quality.
AB - It is well documented that both epidermal growth factor (EGF) and glial cell line
derived neurotrophic factor (GDNF) are critical for porcine oocyte maturation,
however, little information is known about their mechanism of action in vitro. To
gain insight into the mechanisms of action of the optimum doses of EGF and GDNF
on porcine oocyte maturation, porcine cumulus-oocyte complexes (COCs) were
matured in defined porcine oocyte medium supplemented with EGF, GDNF or a
combination of both at varying concentrations (0-100 ng/ml) for 44 h. Nuclear and
cytoplasmic maturation were determined in terms of nuclear stage after DNA
staining with Hoechst and cortical granule distribution after lectin labeling,
respectively. Mature oocytes were subsequently collected for gene expression
analysis or subjected to in vitro fertilization and cultured for 7 days. The
results showed that EGF and/or GDNF, when administered in a certain dose (50
ng/MUl) to the maturation medium, not only effectively improved the
synchronization of nuclear and cytoplasmic maturation processes within the
oocyte, but enhanced expression of their corresponding receptors in mature
oocytes (P < 0.05). Moreover, supplementation with an optimal combination of EGF
+ GDNF resulted in elevation of TFAM transcripts as well as a decrease of caspase
3 transcripts compared with the other studied groups (P < 0.05). Collectively,
our results indicate that treatment of porcine oocytes with specific-dose
combinations of EGF and GDNF stimulates oocyte quality and competence by
transcriptional modulation of genes involved in oocyte survival and competence.
PMID- 28693649
TI - Morphological and molecular characterization of Tarantobelus arachnicida gen. n.,
sp. n. (Nematoda, Rhabditida, Brevibuccidae), a parasitic nematode of tarantulas.
AB - A new genus and new species, Tarantobelus arachnicida, was found in the oral
opening of tarantula spiders bred in captivity in Poland. The new species is
characterized by having a small body (0.77-0.95 mm long in females and 0.66-0.84
mm in males), cuticle poorly annulated by transverse incisures, lateral field
inconspicuous, lips separated with small cuticular flaps topping each lip, stoma
panagrolaimoid with gymnostom well developed with robust and refringent rhabdia,
pharynx panagrolaimoid with isthmus slightly longer than the basal bulb,
intestine with cardiac (anterior) and rectal (posterior) areas with narrower
walls. Mature females with intestinal cells including needle crystal packs,
excretory pore at isthmus level, female reproductive system panagrolaimoid with
post-vulval sac 0.4-0.8 times the length of the corresponding body diameter and
having very thick walls, vulva very prominent, female rectum 0.8-1.3 times the
length of the anal body diameter, female tail conical with acute tip with
phasmids at 58-62% of its length. Male tail conical with long and thin mucro,
spicules ventrad bent having rounded manubrium and thick gubernaculum.
Description, measurements and illustrations of the new species are provided.
Molecular analyses show its relationship with Brevibucca and Cuticonema. On the
other hand, Medibulla and its corresponding subfamily Medibullinae, previously in
Osstellidae, are transferred to Panagrolaimidae, being Shahnematinae, the junior
synonym of Medibullinae. Indocephalobus, recently proposed and located in the
family Panagrolaimidae, is considered a junior synonym of Diplogastrellus
(Diplogasteromorpha), and its only species, I. zebrae, is considered a junior
synonym of D. gracilis. In addition, a key to identification of panagrolaimoid
genera is included.
PMID- 28693650
TI - Assessing Efficacy of Lipid in Unstable, Non-LAST Overdose Patients.
PMID- 28693651
TI - Models of care for traumatically injured patients at trauma centres in British
Columbia: variability and sustainability.
AB - BACKGROUND: Successful trauma systems employ a network of variably-resourced
hospitals, staffed by experienced providers, to deliver optimal care for injured
patients. The "model of care"-the manner by which inpatients are admitted and
overseen, is an important determinant of patient outcomes. OBJECTIVES: To
describe the models of inpatient trauma care at British Columbia's (BC's) ten
adult trauma centres, their sustainability, and their compatibility with
accreditation guidelines. METHODS: Questionnaires were distributed to the trauma
medical directors at BC's ten Level I-III adult trauma centres. Follow-up semi
structured interviews clarified responses. RESULTS: Three different models of
inpatient trauma care exist within BC. The "admitting trauma service" was a
multidisciplinary team providing exclusive care for injured patients. The "on
call consultant" assisted with Emergency Department (ED) resuscitation before
transferring patients to a non-trauma admitting service. The single "short-stay
trauma unit" employed on-call consultants who also oversaw a 48-hour short-stay
ward. Both level I trauma centres utilized the admitting trauma service model
(2/2). All Level II sites employed an on-call consultant model (3/3), deviating
from Level II trauma centre accreditation standards. Level III sites employed all
three models in similar proportions. None of the on-call consultant sites
believed their current care model was sustainable. Inadequate compensation,
insufficient resources, and difficulty recruiting physicians were cited barriers
to sustainability and accreditation compliance. CONCLUSIONS: Three distinct
models of care are distributed inconsistently across BC's Level I-III trauma
hospitals. Greater use of admitting trauma service and short-stay trauma unit
models may improve the sustainability and accreditation compliance of our trauma
system.
PMID- 28693652
TI - Professional caregivers' experiences with the Liverpool Care Pathway in dementia:
An ethnographic study in a Dutch nursing home.
AB - : ABSTRACTObjective:There are few studies on how professional caregivers apply
the Liverpool Care Pathway (LCP) in nursing home care for people with dementia.
Further, despite critiques in the United Kingdom, the LCP continues to be used in
the Netherlands, while, to the best of our knowledge, no studies have been
conducted since its implementation. The purpose of the present study was to
analyze professional caregivers' experiences with the LCP in this context.
METHOD: This article draws on an ethnographic study. Data collection was based on
4 months of ethnographic fieldwork in 2015 in 11 psychogeriatric units of a
nursing home in a rural area of the Netherlands. Data collection included
participant observation and 25 semistructured audiotaped interviews with
specialist elderly care physicians, nursing staff, and a nurse practitioner.
RESULTS: We found that professional caregivers appreciate the LCP as a
communication tool and as a reminder of care goals. However, the document was
deemed too complicated and to cause duplication of work. It was also reported
that the LCP did not cover the complexity of care needs that emerge in practice.
Actual care needs were prioritized over the LCP, which calls its contribution
into question. SIGNIFICANCE OF RESULTS: Overall, the LCP does not match the
context of dementia care in the nursing home. While it could be argued that the
LCP does not intend to replace good care, its benefits as a reminder and a
communication tool need continued consideration in relation to the amount of work
it requires as a bureaucratic obligation.
PMID- 28693653
TI - A methodology framework for weighting genetic traits that impact greenhouse gas
emission intensities in selection indexes.
AB - A methodological framework was presented for deriving weightings to be applied in
selection indexes to account for the impact genetic change in traits will have on
greenhouse gas emissions intensities (EIs). Although the emission component of
the breeding goal was defined as the ratio of total emissions relative to a
weighted combination of farm outputs, the resulting trait-weighting factors can
be applied as linear weightings in a way that augments any existing breeding
objective before consideration of EI. Calculus was used to define the parameters
and assumptions required to link each trait change to the expected changes in EI
for an animal production system. Four key components were identified. The
potential impact of the trait on relative numbers of emitting animals per
breeding female first has a direct effect on emission output but, second, also
has a dilution effect from the extra output associated with the extra animals.
Third, each genetic trait can potentially change the amount of emissions
generated per animal and, finally, the potential impact of the trait on product
output is accounted for. Emission intensity weightings derived from this equation
require further modifications to integrate them into an existing breeding
objective. These include accounting for different timing and frequency of trait
expressions as well as a weighting factor to determine the degree of selection
emphasis that is diverted away from improving farm profitability in order to
achieve gains in EI. The methodology was demonstrated using a simple application
to dairy cattle breeding in Ireland to quantify gains in EI reduction from
existing genetic trends in milk production as well as in fertility and survival
traits. Most gains were identified as coming through the dilution effect of
genetic increases in milk protein per cow, although gains from genetic
improvements in survival by reducing emissions from herd replacements were also
significant. Emission intensities in the Irish dairy industry were estimated to
be reduced by ~5% in the last 10 years because of genetic trends in production,
fertility and survival traits, and a further 15% reduction was projected over the
next 15 years because of an observed acceleration of genetic trends.
PMID- 28693654
TI - Cut and rip and cut alone techniques versus usual practice in the removal of
trauma patient clothing.
AB - : IntroductionRapid exposure of a trauma patient is an essential component of the
primary survey. No gold standard exists regarding the best technique to remove
clothing from a trauma patient. The purpose of this study is to compare two
techniques of clothing removal versus usual practice using standard trauma
shears. METHODS: Advanced Care Paramedic (ACP) students were randomized to either
the Cut and Rip (CAR) or Cut Alone (CAL) techniques to remove clothing from a
standardized trauma mannequin. Practicing paramedics were recruited to remove
clothing from the mannequin using Usual Practice (UP). Total time and time for
removal of individual pieces of clothing was recorded. RESULTS: Twenty-four
participants (8 per group) were recruited to participate. The student groups
(CAR, CAL) were similar in mean age (29, 27), years of practice (1 student >5
years) and male gender (63, 43%). The UP group was older (mean 34), more
experienced (63% practice >5 years), and had a higher level of training (63% ACP)
but a similar percentage of males (63%). Removal time was significantly less in
the CAR group compared to the CAL group (mean 104 seconds, 95% CI 88-120 vs. mean
136 seconds, 95% CI 119-154, p=0.02). Removal times in the UP group were not
significantly different from the other groups (mean 124 seconds, 95% CI 108-140,
p>0.05). CONCLUSION: The CAR technique is faster than both CAL and UP groups to
remove clothing from a standard trauma mannequin.
PMID- 28693656
TI - Resolution of Carbapenemase-Producing Klebsiella pneumoniae Outbreak in a
Tertiary Cancer Center; the Role of Active Surveillance.
PMID- 28693655
TI - Longitudinal Assessment of Self- and Informant-Subjective Cognitive Complaints in
a Sample of Healthy Late-Middle Aged Adults Enriched with a Family History of
Alzheimer's Disease.
AB - OBJECTIVES: The purpose of this study was to investigate the longitudinal
trajectory of self- and informant-subjective cognitive complaints (SCC), and to
determine if SCC predict longitudinal changes in objective measures (OM) of
cognitive function. METHODS: The study included healthy and cognitively normal
late middle-aged adults enriched with a family history of AD who were evaluated
at up to three visits over a 4-year period. At each visit (Visit 1-3), self- and
informant-SCC and OM were evaluated. Linear mixed models were used to determine
if the longitudinal rate of change of self- and informant-SCC were associated
with demographic variables, depressive symptoms, family history (FH), and
apolipoprotein epsilon 4 (APOE4) status. The same modeling approach was used to
examine the effect of Visit 1 SCC on longitudinal cognitive change after
controlling for the same variables. RESULTS: At Visit 1, more self-SCC were
associated with fewer years of education and more depressive symptoms. SCC were
also associated with poorer performance on cognitive measures, such that more
self-SCC at Visit 1 were associated with poorer performance on memory and
executive functioning measures at Visit 1, while more informant-SCC were
associated with faster rate of longitudinal decline on a measure of episodic
learning and memory. FH and APOE4 status were not associated with SCC.
DISCUSSION: Self- and informant-SCC showed an association with OM, albeit over
different time frames in our late middle-aged sample. Additional longitudinal
follow-up will likely assist in further clarifying these relationships as our
sample ages and more pronounced cognitive changes eventually emerge. (JINS, 2017,
23, 617-626).
PMID- 28693657
TI - Environmental Surfaces in Healthcare Facilities are a Potential Source for
Transmission of Candida auris and Other Candida Species.
AB - Contaminated surfaces have been implicated as a potential route for dissemination
of the emerging multidrug-resistant fungal pathogen Candida auris. In laboratory
testing, C. auris and other Candida species persisted for 7 days on moist or dry
surfaces. Candida species were recovered frequently from the hospital
environment, particularly from moist surfaces. Infect Control Hosp Epidemiol
2017;38:1107-1109.
PMID- 28693658
TI - Patient Hand Colonization With MDROs Is Associated with Environmental
Contamination in Post-Acute Care.
AB - We assessed multidrug-resistant organism (MDRO) patient hand colonization in
relation to the environment in post-acute care to determine risk factors for MDRO
hand colonization. Patient hand colonization was significantly associated with
environmental contamination. Risk factors for hand colonization included
disability, urinary catheter, recent antibiotic use, and prolonged hospital stay.
Infect Control Hosp Epidemiol 2017;38:1110-1113.
PMID- 28693659
TI - What's Lurking Around the Corner? Polymyxin B Resistance Among Klebsiella
pnemoniae carbapenemase-producing Enterobacteriaceae, and Others, as a Burden of
Use.
PMID- 28693660
TI - What's In A Name? A "Cluster" Of Hospital Epidemiologists.
PMID- 28693661
TI - Bacterial strain changes during chronic otitis media surgery.
AB - OBJECTIVE: Cultures obtained from pre-operative middle-ear swabs from patients
with chronic otitis media have traditionally been used to guide antibiotic
selection. This study investigated changes in the bacterial strains of the middle
ear during chronic otitis media surgery. METHODS: Pre-operative bacterial
cultures of otorrhoea, and peri-operative cultures of the granulation tissue in
either the middle ear or mastoid cavity, were obtained. Post-operative cultures
were selectively obtained when otorrhoea developed after surgery. RESULTS:
Bacterial growth was observed in 45.5 per cent of pre-operative cultures, 13.5
per cent of peri-operative cultures and 4.5 per cent of post-operative cultures.
Methicillin-resistant Staphylococcus aureus was identified as the most common
bacteria in all pre-operative (32.4 per cent), peri-operative (52.4 per cent) and
post-operative (71.4 per cent) tests, and the percentage of Methicillin-resistant
S aureus increased from the pre- to the post-operative period. CONCLUSION: The
bacterial culture results for post-operative otorrhoea showed low agreement with
those for pre-operative or peri-operative culture, and strain re-identification
was required.
PMID- 28693662
TI - Growing without a mother results in poorer sexual behaviour in adult rams.
AB - The aim of this study was to determine if the absence of the mother during
rearing has long-term effects on sexual behaviour and physiological reproductive
parameters of adult rams. Two groups of rams were: (1) artificially reared,
separated from their dams 24 to 36 h after birth (Week 0) and fed using sheep
milk until 10 weeks of age (group AR, n=14); and (2) reared by their dams until
10 weeks of age (group DR, n=13). Sexual behaviour (tests of 20 min) and
physiological reproductive parameters were analysed separately for the non
breeding (Weeks 42 to 64) and the breeding (Weeks 66 to 90) seasons. Body weight,
scrotal circumference, gonado-somatic index, testosterone concentrations or sperm
parameters were similar in both rearing conditions (AR v. DR) in both seasons.
During the non-breeding season AR rams displayed fewer ano-genital sniffings (AR:
4.2+/-0.4 v. DR: 5.3+/-0.4, P=0.04) and matings (AR: 1.2+/-0.2 v. DR: 1.8+/-0.2,
P=0.002) than DR rams. During the breeding season AR rams displayed fewer ano
genital sniffings (AR: 4.3+/-0.5 v. DR: 5.7+/-0.5, P=0.005), flehmen (AR: 0.7+/
0.2 v. DR: 1.1+/-0.2, P=0.03), mount attempts (AR: 1.4+/-0.2 v. DR: 2.1+/-0.2,
P=0.04), and tended to mount less frequently (AR: 6.6+/-0.9 v. DR: 8.8+/-0.9,
P=0.08) than DR rams. In conclusion, the absence of the mother during the rearing
period negatively affected display of sexual behaviour towards oestrous ewes
during a rams adult life in both breeding and non-breeding seasons. However, it
did not affect testis size, testosterone secretion or sperm variables.
PMID- 28693663
TI - Is SpxA2 involved in hydrogen peroxide production and competence development in
Streptococcus sanguinis?
AB - PURPOSE: The objective of the present study was to investigate whether
Streptococcus sanguinis SpxA2 plays a role in competence development and
endogenous H2O2 generation, and whether the SpxA2 Cys10-XX-Cys13 (CXXC) motif is
involved in competence development. METHODOLOGY: The competence development of
wild-type S. sanguinis (SK36) and its derivatives was compared by transformation
efficiency assay and real-time RT-PCR. The spx allele mutants, spxA2 (C10A) and
spxA2 (C13A), were constructed by site-directed mutagenesis. The Deltapox mutant
was treated with 1 mM H2O2 to exclude the effect of other Pox products on
competence development. RESULTS: Compared with the wild-type (4.42+/-0.58*10-4),
the DeltaspxA2 mutant showed decreased transformation efficiency (0.07+/-0.03*10
4). Furthermore, there was a 2- to 15-fold reduction in DeltaspxA2 mutant com
gene expression. SpxA2 was able to down-regulate endogenous H2O2 generation by
repressing pox expression. Additionally, endogenous H2O2 negatively regulated
competence without affecting spxA2 expression. The Deltapox mutant increased com
gene expression (2- to 8-fold), but the 1 mM H2O2-treated Deltapox mutant showed
decreased com gene expression. Interestingly, the DeltaspxA2Deltapox mutant
showed enhanced competence-associated parameters. The fact that spxA2 (C10A) and
spxA2 (C13A) behaved like the DeltaspxA2 mutant revealed the role of the CXXC
motif in competence development. CONCLUSION: Although the intricate relationship
between SpxA2, pox-mediated H2O2 production and competence development was
clarified in S. sanguinis, it would be worthwhile to explore further whether H2O2
is involved in competence development through oxidizing the SpxA2 CXXC motif.
PMID- 28693664
TI - Parafilimonas rhizosphaerae sp. nov., isolated from the rhizosphere of tomato
plant (Solanum lycopersicum L.).
AB - A bacterial strain, designated T16E-198T, was isolated from the rhizosphere of
tomato plant collected from a farm on Buyeo-gun, Chungcheongnam-do, South Korea.
The strain was aerobic, Gram-stain-negative, rod-shaped, non-flagellated and
yellow-pigmented. Strain T16E-198T was mesophilic, catalase- and oxidase-positive
and with flexirubin-type pigments. A phylogenetic tree based on 16S rRNA gene
sequences showed that strain T16E-198T formed a lineage with Parafilimonas terrae
5GHs7-2T, sharing highest sequence similarity of 98.4 % with it and less than 93
% with all the other validly published species. The major fatty acids were iso
C15 : 0, iso-C17 : 0 3-OH and iso-C15 : 1 G. The predominant menaquinone was MK
7. The polar lipids were phosphatidylethanolamine, one unknown aminophospholipid,
five unknown aminolipids and five unknown lipids. The DNA G+C content was 41.2
mol%. On the basis of the phenotypic, phylogenetic and chemotaxonomic data
presented, strain T16E-198T is considered to represent a novel species of the
genus Parafilimonas, for which the name Parafilimonas rhizosphaerae sp. nov. is
proposed; the type strain is T16E-198T (=KACC 18786T=JCM 31601T).
PMID- 28693665
TI - Characterization of high level ampicillin- and aminoglycoside-resistant
enterococci isolated from non-hospital sources.
AB - PURPOSE: High level ampicillin- and aminoglycoside-resistant enterococci are
being increasingly reported from non-hospital sources. This study was carried out
to characterize these strains from non-hospital sources in Nigeria. METHODOLOGY:
A collection of Enterococcus faecium isolated from vegetables, soil, farm animals
and manure and observed to be resistant to ampicillin (n=63) and gentamicin
(n=37) discs, were screened for resistance to high levels of ampicillin and
aminoglycoside using E-test strips. Putative high level ampicillin- and
aminoglycoside-resistant strains were screened for pbp5 and aminoglycoside
modifying enzyme genes, respectively, by PCR. The C-terminal region of the
amplified pbp5 gene was also sequenced. RESULTS: Five (5/63) and thirty-five
(35/37) of the ampicillin- and aminoglycoside-resistant strains were identified
as high level ampicillin- and aminoglycoside-resistant E. faecium strains,
respectively, based on the MIC results. The amplified pbp5 gene from the high
level ampicillin-resistant isolates displayed 96-99 % nucleotide sequence
similarity with the reference strains and three novel insertions (500Glu->Leu,
502Asp->Arg and 614Ile->Phe) in the amino acid sequence. Aminoglycoside modifying
enzyme genes aac(6')-Ie-aph(2") (100 %), aph(2')-Ic (88.8 %), aph(3')-IIIa (90 %)
and ant(4')-Ia (40 %) were detected among the high level aminoglycoside-resistant
isolates. CONCLUSION: This is the first report on the characterization of high
level ampicillin- and aminoglycoside-resistant Enterococcus faecium among animals
and vegetables in Nigeria. The results show that non-hospital sources can
constitute a reservoir for potential dissemination of these strains and genes to
humans via the food chain or by direct contact.
PMID- 28693666
TI - Evaluation of recombinant factor C assay for the detection of divergent
lipopolysaccharide structural species and comparison with Limulus amebocyte
lysate-based assays and a human monocyte activity assay.
AB - PURPOSE: The Limulus amebocytelysate (LAL) assay is widely used for the screening
of lipopolysaccharide (LPS) in parenteral pharmaceuticals. However, correlation
of LPS in Gram-negative bacterial infections by LAL assay has been problematic,
partly due to the variable reactivity of different LPS structures. Recombinant
factor C (rFC) has allowed the development of a new simple, specific and
sensitive LPS detection system (PyroGene). In this work, the potential of the new
assay for detecting various LPS structures has been investigated and compared
with two LAL-based assays and a human monocyte activity assay. METHODOLOGY: The
activity of the various LPS structures has been investigated by PyroGene and two
LAL-based assays and a human monocyte activity assay. RESULTS: The rFC assay
detected most LPS structures in picogram quantities and the potency of E. coli,
B. cepacia, Salmonella smooth and Salmonella R345 LPS was no different when
measured with PyroGene or LAL assays. However, the reactivity of K. pneumoniae,
S. marcescens, B. pertussis and P. aeruginosa LPS differed significantly between
these assays. Importantly, pairwise correlation analysis revealed that only the
PyroGene assay produced a significant positive correlation with the release of IL
6 from a monocytic cell line. CONCLUSION: We conclude that the rFC-based assay is
a good replacement for conventional LAL assays and as it correlates significantly
with IL-6 produced by a human monocyte cell line it could potentially be more
useful for detecting LPS in a clinical setting.
PMID- 28693667
TI - Distribution of Chlamydia trachomatis genotypes in neonatal conjunctivitis in
Hungary.
AB - The objective of the present study was to determine the frequency and age
distribution of different Chlamydia trachomatis (CT) genotypes causing ophthalmia
neonatorum (ON) in Hungary. Using CT specific PCR, we tested 76 conjunctival
samples from symptomatic infants up to 3 months old in the National Centre for
Epidemiology, Budapest between 2008 and 2016. CT tested positive in 30 of 76
conjunctival samples (39.5 %). The sequencing of the positive samples was
successful in every case but one, and resulted in 48 % dominance for genotype E
(14/29), followed by 24 % for genotype G (7/29), 10 % for J (3/29), 6.9 % for K
and F (2/29), and 3.4 % for H (1/29). CT must still be regarded as a common
pathogen causing ON in Hungary. Routine screening and treatment of pregnant women
can be recommended to prevent these conditions. Chronic ON cases can be reduced
by early diagnosis. Further research is needed to explain the dominance of
genotypes E and G.
PMID- 28693668
TI - Mesorhizobium helmanticense sp. nov., isolated from Lotus corniculatus nodules.
AB - In this study, three strains belonging to the genus Mesorhizobium, CSLC115NT,
CSLC19N and CSLC37N, isolated from Lotus corniculatus nodules in Spain, were
characterized. Their 16S rRNA gene sequences were closely related to those of
Mesorhizobium metallidurans STM 2683T, Mesorhizobium tianshanense A-1BST,
Mesorhizobium tarimense CCBAU 83306T, Mesorhizobium gobiense CCBAU 83330T and
Mesorhizobium caraganae CCBAU 11299T with similarity values higher than 99.7 %.
The analysis of concatenated recA and glnII genes showed that the most closely
related type strains were M. metallidurans STM 2683T, M. tianshanense A-1BST and
M. tarimense CCBAU 83306T with 96, 95 and 94 % similarity values in the recA gene
and 95, 94 and 94 % in the glnII gene, respectively. M. metallidurans LMG 24485T,
M. tianshanense USDA 3592T and M. tarimense LMG 24338T showed means of 44, 41 and
42 % DNA-DNA relatedness, respectively, with respect to strain CSLC115NT. The
major fatty acids were those from summed feature 8 (C18 : 1omega7c/C18 :
1omega6c), C16 : 0 and C18 : 1omega7c 11-methyl. The results of phenotypic
characterization support that the L. corniculatus nodulating strains analysed in
this work belong to a novel species of the genus Mesorhizobium for which the name
Mesorhizobium helmanticense sp. nov. is proposed, and the type strain is
CSLC115NT (= LMG 29734T=CECT 9168T).
PMID- 28693669
TI - Foreword to the special issue commemorating Volume 100 of Science Progress.
PMID- 28693670
TI - The Right to Food and the Planetary Boundaries framework.
AB - The 'Right to Food' is a legal entitlement owed to all human beings established
in international law more than half a century ago. Fulfilment of the right has
been entrusted to states parties to the 1966 International Covenant on Economic,
Social and Cultural Rights (ICESCR). However, in practice, the right is often
breached because of hostility or indifference from individuals or institutions
refusing access to provisions, or because of vicissitudes of nature. Adverse
impacts due to human interference in natural processes are increasingly
noticeable in the area of food production. These processes have been classified
into nine distinct categories, all of which need be kept within certain margins,
so-called 'Planetary Boundaries', which delineate a safe operating space for
humanity. This paper discusses the impact each of these human-induced
developments has on the provision of food as well as the other way round and what
the consequences would be if the boundaries were exceeded. Yet there are means of
keeping the worst consequences of most of these processes at bay. The paper
explores some of these.
PMID- 28693671
TI - 100 years of X-ray crystallography.
AB - The developments in crystallography, since it was first covered in Science
Progress in 1917, following the formulation of the Bragg equation, are described.
The advances in instrumentation and data analysis, coupled with the application
of computational methods to data analysis, have enabled the solution of molecular
structures from the simplest binary systems to the most complex of biological
structures. These developments are shown to have had major impacts in the
development of chemical bonding theory and in offering an increasing
understanding of enzyme-substrate interactions. The advent of synchrotron
radiation sources has opened a new chapter in this multi-disciplinary field of
science.
PMID- 28693672
TI - Inceptions of biomathematics from Lotka to Thom.
AB - Mathematical biology occupies a special place at the interface between the
physical, mathematical and life sciences. Is this interface merely a meeting
point for dabblers venturing out of their own proper domains to work on problems
of mutual interest? Or is it an incipient science in its own right, with its own
particular character, principles, and practices? The past century has seen vast
advances in the application of mathematical and physical ideas and techniques to
biological problems, in the process transforming many of them almost beyond
recognition. Nonetheless, the question of a biomathematics as a new kind of
science remains open, despite several fascinating, if sometimes problematic,
attempts.
PMID- 28693673
TI - A hundred years in the elucidation of the structures of natural products.
AB - The development in the strategies for elucidating the structures of natural
products from 1916 to 2016 are reviewed revealing the transition from chemical to
spectroscopic methods and using examples drawn from the chemistry of terpenoids
and steroids.
PMID- 28693674
TI - The imperative for regenerative agriculture.
AB - A review is made of the current state of agriculture, emphasising issues of soil
erosion and dependence on fossil fuels, in regard to achieving food security for
a relentlessly enlarging global population. Soil has been described as "the
fragile, living skin of the Earth", and yet both its aliveness and fragility have
all too often been ignored in the expansion of agriculture across the face of the
globe. Since it is a pivotal component in a global nexus of soil-water-air
energy, how we treat the soil can impact massively on climate change - with
either beneficial or detrimental consequences, depending on whether the soil is
preserved or degraded. Regenerative agriculture has at its core the intention to
improve the health of soil or to restore highly degraded soil, which
symbiotically enhances the quality of water, vegetation and land-productivity. By
using methods of regenerative agriculture, it is possible not only to increase
the amount of soil organic carbon (SOC) in existing soils, but to build new soil.
This has the effect of drawing down carbon from the atmosphere, while
simultaneously improving soil structure and soil health, soil fertility and crop
yields, water retention and aquifer recharge - thus ameliorating both flooding
and drought, and also the erosion of further soil, since runoff is reduced. Since
food production on a more local scale is found to preserve the soil and its
quality, urban food production should be seen as a significant potential
contributor to regenerative agriculture in the future, so long as the methods
employed are themselves 'regenerative'. If localisation is to become a dominant
strategy for dealing with a vastly reduced use of fossil fuels, and preserving
soil quality - with increased food production in towns and cities - it will be
necessary to incorporate integrated ('systems') design approaches such as
permaculture and the circular economy (which minimise and repurpose 'waste')
within the existing urban infrastructure. In addition to growing food in urban
space, such actions as draught-proofing and thermally insulating existing
building stock, and living/ working on a more local scale, would serve well to
cut our overall energy consumption. In order to curb our use of fossil fuels,
methods for reducing overall energy use must be considered at least equally
important to expanding low-carbon energy production. In synopsis, it is clear
that only by moving from the current linear, 'take, make, dispose (waste
creation)' model for resource-consumption, to the systemic, circular alternative
of 'reduce, reuse, recycle, regenerate', are we likely to meet demands for future
generations.
PMID- 28693675
TI - The Chemistry Department at Imperial College London: A History, 1845-2000.
PMID- 28693676
TI - Matter - a current picture.
AB - A century ago, a two-part review by W. C. McC. Lewis entitled "The Structure of
Matter" appeared in this journal, surveying the achievements that had been made
to date in that field. Topics included the value of Avogadro's constant, the
dimensions of a molecule, equations of state for non-ideal gases, then-current
theories relating electron configurations to the Periodic Law, the then-new
nuclear atom model of Rutherford, and the first findings from X-ray
crystallographic studies of matter, a field then in its nascent phase. This
article is a sequel to that work. As a vast quantity of research has been
addressed to the topic in the intervening period, the view presented here can at
best be selective and idiosyncratic. Nonetheless, it attempts to capture some of
the important strides in 'matter science', broadly defined, over the past
century, highlight some recent areas of interest or novelty, and give a picture
of some of the mysteries that remain.
PMID- 28693677
TI - Directed panspermia: a 21st century perspective.
AB - Applying 21st century technology to the design and development of a hypothetical
extra-terrestrial colonisation programme, we reimagine 'directed panspermia' from
the perspective of Crick and Orgel's 'technological society', 44 years after the
publication of their original landmark paper.
PMID- 28693678
TI - Some contributions of organic chemistry to the study of the biosynthesis of
natural products.
AB - The development over the last 100 years of organic chemists' contributions to the
understanding of the biosynthesis of natural products is reviewed. The
transitions from speculation to labelling experiments and to the current role of
genomics are exemplified, particularly from terpenoid biosynthesis.
PMID- 28693679
TI - Photoinduced charge transfer: from photography to solar energy.
AB - To celebrate the centenary of Science Progress we offer a short survey of the
progress made over the past one hundred years in the research and application of
photoinduced charge transfer. After a brief historical overview and introduction
to photoinduced charge transfer, we discuss developments in the theory and
practice of photography, photovoltaics, photocatalysis, fluorescent probes and
chemosensing.
PMID- 28693680
TI - The global oil supply - prevailing situation and prognosis.
PMID- 28693681
TI - Proposal for transfer of Oceanibulbus indolifex Wagner-Dobler et al. 2004 to the
genus Sulfitobacter as Sulfitobacter indolifex comb. nov.
AB - A polyphasic taxonomic study was undertaken to clarify the exact position of type
strain HEL-45T of OceanibulbusindolifexWagner-Dobler et al. 2004. A combination
of physiological properties of HEL-45T were similar to those of its closest
relatives, Sulfitobacterdelicatus KMM 3584T and Sulfitobacterdubius KMM 3554T.
The results of 16S rRNA gene sequences analysis indicated that HEL-45T and the
two relatives shared 99.6 % similarity and formed a coherent cluster in the
phylogenetic tree. The close relationship between HEL-45T and the two relatives
was underpinned by the results for chemotaxonomic characters, including the fatty
acids, quinone and polar lipids. The digital DNA-DNA hybridization values and
between HEL-45T and the two relatives were 25.9 and 31.6 %, respectively, which
were well below the 70 % threshold value recommended for delineation of bacterial
species. The comparative phenotypic and genotypic analyses supported the
incorporation of Oceanibulbusindolifex into the genus Sulfitobacter as
Sulfitobacterindolifex comb. nov.; the type strain is HEL-45T (=MCCC 1A11773T=DSM
14862T=NCIMB 13983T).
PMID- 28693682
TI - International Committee on Systematics of Prokaryotes Subcommittee on the
taxonomy of Mollicutes. Minutes of the closed meeting, 3rd July 2016, Brisbane,
Australia.
PMID- 28693683
TI - Description of a phototrophic bacterium, Thiorhodococcus alkaliphilus sp. nov.
AB - Strain JA878T was purified from a photoheterotrophic enrichment obtained from a
sediment sample of a brown pond near Nari Salt Pan, Bhavnagar, Gujarat, India.
Cells of the isolate were coccoid, motile by means of single polar flagellum and
Gram-stain-negative. The internal photosynthetic membrane architecture was
vesicular. Strain JA878T contained bacteriochlorophyll a and spirilloxanthin
series of carotenoids with rhodopin (>85 %) as the major component. Strain JA878T
grew optimally at pH 10-11, and had no requirement for NaCl (tolerated up to 6 %,
w/v) or vitamins for growth. C16 : 1omega7c/C16 : 1omega6c, C18 : 1omega7c/C18 :
1omega6c and C16 : 0 were identified as the major fatty acids (>10 %).
Phosphatidylglycerol, phosphatidylethanolamine, aminophospholipid and an unknown
polar lipid were identified. Q8 was the predominant quinone system in strain
JA878T. The DNA G+C content was 62.4 mol%. Highest 16S rRNA gene sequence
similarity through EzTaxon-based blast analysis of strain JA878T was found with
the type strains of Thiorhodococcus fuscus (99 %), Thiorhodococcus kakinadensis
(98.6 %), Thiohalobacter thiocyanaticus (98.4 %), Thiophaeococcus fuscus (97.3 %)
and other members of the class Gammaproteobacteria (<97.3 %), revealing a close
affiliation to the genera Thiorhodococcus, Thiohalobacter and Thiophaeococcus.
However, the phylogenetic treeing firmly placed the strain in the genus
Thiorhodococcus. Phenotypic and chemotaxonomic evidence supported the affiliation
of strain JA878T to the genus Thiorhodococcus and not to Thiohalobacter,
Thiophaeococcus or other known genera of Chromatiaceae. Distinct physiological,
genotypic and chemotaxonomic differences indicate that strain JA878T represents a
novel species of the genus Thiorhodococcus, for which the name Thiorhodococcus
alkaliphilus sp. nov. is proposed. The type strain is JA878T (=KCTC 15531T=JCM
31245T).
PMID- 28693684
TI - Clostridium tepidum sp. nov., a close relative of Clostridium sporogenes and
Clostridium botulinum Group I.
AB - Obligately anaerobic, Gram-stain-positive, spore-forming bacteria
indistinguishable by pulsed-field gel electrophoresis were isolated from non
dairy protein shakes in bloated bottles. One of the isolates, strain IEH 97212T,
was selected for further study. The strain was closely related to Clostridium
sporogenes and Clostridium botulinum Group 1 based on 16S rRNA gene sequence
similarities. Phylogenetic analysis also showed that strain IEH 97212T and strain
PE (=DSM 18688), a bacterium isolated from solfataric mud, had identical 16S rRNA
gene sequences. Strains IEH 97 212T and DSM 18 688 were relatively more
thermophilic (temperature range for growth: 30-55 degrees C) and less
halotolerant [growth range: 0-2.5 % (w/v) NaCl] than C. sporogenes and C.
botulinum. They were negative for catalase, oxidase, urease and l-pyrrolidonyl
arylamidase and did not produce indole. The strains produced acid from d-glucose,
maltose and trehalose, and hydrolysed gelatin, but did not hydrolyse aesculin.
The end-products of growth included acetic acid, propionic acid, butyric acid,
isobutyric acid, valeric acid, isovaleric acid, isocaproic acid, phenylpropionic
acid, 2-piperidinone, 2-pyrrolidinone and gas(es). The predominant fatty acids
were C14 : 0, C16 : 0 and C18 : 1omega9c. The genomic DNA G+C content of strains
IEH 97212T and DSM 18688 was 26.9 and 26.7 mol%, respectively. According to the
digital DNA-DNA hybridization data, the relatedness of these strains was 98.4 %,
while they showed only 35.7-36.0 % relatedness to C. sporogenes. Based on the
results of this polyphasic study, these strains represent a novel species, for
which the name Clostridium tepidum sp. nov. is proposed, with the type strain IEH
97212T (=NRRL B-65463T=DSM 104389T).
PMID- 28693685
TI - Effect of involved Aspergillus species on galactomannan in bronchoalveolar lavage
of patients with invasive aspergillosis.
AB - PURPOSE: The detection of galactomannan (GM) in bronchoalveolar lavage (BAL)
fluid is an important surrogate marker for the early diagnosis and therapeutic
monitoring of invasive aspergillosis (IA), regardless of the involved species of
Aspergillus. Here, we utilized the Platelia Aspergillus GM enzyme immunoassay
(Bio-Rad) to evaluate the GM index in BAL fluid samples from patients with
proven, probable or putative IA due to Aspergillusflavus versus
Aspergillusfumigatus. METHODOLOGY: In a prospective study between 2009 and 2015,
116 BAL samples were collected from suspected IA patients referred to two
university hospitals in Tehran, Iran. KEY FINDINGS: According to European
Organization for Research and Treatment of Cancer and Mycoses Study Group and
Blot criteria, 35 patients were classified as IA patients, of which 33 cases
tested positive for GM above 0.5 and, among these patients, 22 had a GM index
>=1. Twenty-eight were culture positive for A. flavus and seven for A. fumigatus.
The GM index for A. flavus cases was between 0.5-6.5 and those of A. fumigatus
ranged from 1 to 6.5. The sensitivity and specificity of a GM index >=0.5 in
cases with A. flavus were 86 and 88 % and for A. fumigatus patients were 100 and
73 %, respectively. CONCLUSION: Overall, the mean GM index in patients with A.
fumigatus (3.1) was significantly higher than those of A. flavus (1.6; P
value=0.031) and the sensitivity of GM lower for A. flavus when compared to A.
fumigatus. This finding has implications for diagnosis in hospitals and countries
with a high proportion of A. flavus infections.
PMID- 28693686
TI - The Correlation of Indices in r-TEG with Intra-operative Blood Loss in
Neurosurgical Patients.
AB - Objective Intra-operative coagulopathy has a close relationship with blood loss
and the prognosis of patients. Rapid-thrombelastography (r-TEG) is a
comprehensive assessment of coagulation abnormalities and also an effective way
for constructing blood transfusion. This study attempts to investigate the
correlation of r-TEG indices with intra-operative hemorrhage.Methods Patients who
underwent transphenoidal hypophysectomy and craniotomy from January 15 to April
30, 2013 in Peking Union Medical College hospital were recruited. All patients
had pre- and post-operative r-TEG and conventional coagulation tests (CCTs).
Patients' information and intra-operative blood loss as a percentage of estimated
blood volume were recorded. Spearman's correlation analyses were used for
discovering the relationship between indices in r-TEG or CCTs and the intra
operative blood loss. The significant correlated index of r-TEG was further
investigated using linear regression analysis. Results A total of 181 patients
participated in this study. Intra-operative change of alpha-angle, which reflects
the fibrinogen level and function, was the only r-TEG index that correlated with
blood loss significantly (P=0.013, r= -0.184), thus challenging the current
empirical cognition of the effects of intra-operative hemorrhage on coagulation.
As intra-operative blood loss increased, alpha-angle decreased, and every 1% loss
of estimated blood volume (EBV) led to 0.60 degree decrease of alpha-angle. As
for CCT results, changes of fibrinogen and platelet count were also significantly
correlated with blood loss (P=0.015 and P=0.001, respectively).Conclusions Peri
operative change of alpha-angle, as an index of r-TEG, exhibited a significant
negative correlation with intra-operative blood loss. The impact of hemorrhage on
fibrinogen, instead of clotting factors, should be scrutinized.
PMID- 28693687
TI - Abnormal Alterations of Cortical Thickness in 16 Patients with Type 2 Diabetes
Mellitus: A Pilot MRI Study.
AB - Objective The aim of this study is to investigate the cerebral cortical thickness
changes in type 2 diabetes mellitus (T2DM) using a whole brain cortical thickness
mapping system based on brain magnetic resonance imaging (MRI).Methods High
resolution three-dimensional T1-weighted fast spoiled gradient recalled echo MR
images were obtained from 16 patients with T2DM, as well as from 16 normal
controls. The whole brain cortical thickness maps were generated, and the
cortical thickness of each brain region was calculated according to gyral based
regions of interest (ROI) using an automated labeling system by the Freesurfer
software. We compared mean cortical thickness at each brain region by the
analysis of covariance with age and sex as covariates. The regional difference of
the cortical thickness over the whole brain was compared by the analysis of
surface-based cortical thickness.Results Mean cortical thicknesses analysis
showed bilateral cerebrum in the patients with T2DM (left: 2.52+/-0.07 mm; right:
2.51+/-0.08 mm) were significant thinner than those in the normal controls (left:
2.56+/-0.09 mm; right: 2.56+/-0.09 mm) (both P<0.05). Regional cortical thinning
in T2DM was demonstrated in the paracentral lobule, postcentral gyrus, lateral
occipital gyrus, lingual gyrus, precuneus, superior temporal gyrus, middle
temporal gyrus, inferior temporal gyrus and posterior cingulate gyrus, compared
to the normal controls. The cortical thickness of left middle cingulate and right
inferior temporal gyrus were negatively correlated with the disease
course.Conclusion A widespread cortical thinning was revealed in patients with
T2DM by the analysis of brain cortical thickness on MR. Our finding supports the
idea that T2DM could lead to subtle diabetic brain structural changes.
PMID- 28693688
TI - Effects of Aging on the Proliferation and Differentiation Capacity of Human
Periodontal Ligament Stem Cells.
AB - Objective The aim of this study is to investigate the proliferation,
differentiation and apoptosis of periodontal ligament stem cells (PDLSC) derived
from different aged donors, and to evaluate the effects of aging on the
biological characteristics of PDLSC.Methods Periodontal ligament tissues were
obtained from 24 surgically extracted human premolars during orthodontics
therapy. The specimens were divided into three groups according to the donor's
age. Group A: 18-20 years, group B: 30-35 years, group C: 45-50 years. PDLSC were
isolated and cultured using a tissue-block-based enzymolytic method by limiting
dilution assay. The colony forming efficiency of PDLSC for three experimental
groups was determined. Senescence-Associated beta-Galactosidase (SA-beta-G)
expression in the three groups was examined using beta-galactosidase staining
working solution. Cell cycle and apoptosis of the PDLSC were examined by the flow
cytometry. Alkaline phosphatase (ALP) activity was evaluated by ALP staining. The
expression of osteoplastic differentiation related genes Runt-related
transcription factor-2 (Runx-2), Collagen Type 1 (col-1), and ALP of PDLSC were
examined by quantitative real-time RT-PCR.Results The colony forming efficiency
of PDLSC in Group A, B and C was 36.67%, 22.67% and 9.33%, respectively, which
decreased with donors' age (P<0.05). SA-beta-G expression of the senescent PDLSC
in group A, B and C were 4.14%, 16.39%, 50.38%, respectively (P<0.05). Cells in
G2/S phase was 38.73%, 29.88%, 18.25% (P<0.05), and the apoptosis rate was 1.57%,
4.56%, 5.84% (P<0.05), in group A, B and C respectively. The ALP staining in the
three groups decreased with the increase of donors' ages, and the expression of
Runx-2, col-1 and ALP decreased gradually from group A to group C (all P<0.05),
which indicated the osteogenic differentiation capacity of PDLSC decreased while
donor aging.Conclusion Human PDLSC could be successfully isolated from
periodontal ligament tissues of different aged donors. However, the proliferation
and osteogenic differentiation capacity of PDLSC decreased while donor aging.
PMID- 28693689
TI - Neuroprotective Effects of Grape Seed Procyanidin Extract on Ischemia-Reperfusion
Brain Injury.
AB - Objective Oxidative stress (OS) plays a crucial role in ischemic stroke. Grape
seed procyanidin extract (GSPE) was reported to be a critical regulator of OS. We
hypothesized that GSPE might also be protective in ischemia-reperfusion brain
injury. This study aimed to explore whether GSPE administration can protect mice
from ischemia-reperfusion brain injury.Methods Transient middle cerebral artery
occlusion (MCAO) was conducted followed by reperfusion for 24 hours to make
ischemia-reperfusion brain injury in mice that received GSPE (MCAOG, n=60) or
normal saline (MCAONS, n=60). Sham-operated mice (GSPE group and normal saline
group) were set as controls. The neurological severity score (NSS) was used to
evaluate neural function impairment 1 hour, 24 hour, 3 days and 7 days after
MCAO. Mice underwent brain T2WI imaging with a 3T animal MRI scanner 24 hours
after reperfusion, and the stroke volume of brains were calculated according to
abnormal signal intensity. Immunohistopathological analysis of brain tissues at
24 h after reperfusion was performed for neuronal nuclear antigen (NeuN), CD34,
Bcl-2, and Bax. Glutathione peroxidation (GSH-Px) activity and the level of
malonaldehyde (MDA) of brain tissue were also examined. The above indexes were
compared among the groups statistically.Results Significant functional
improvement was observed 24 hours after MCAO in MCAOG group compared to MCAONS
group (P<0.05). MCAOG group had smaller cerebral stroke volume (22.46 +/- 11.45
mm3 vs. 47.84+/-9.06 mm3, P<0.05) than MCAONS group 24 hours after MCAO. More
mature NeuN-immunoreactive neurons and more CD34-positive cells in peri-infarct
zones were observed in brain tissue of MCAOG mice 24 h after MCAO than that of
MCAONS mice (both P<0.05). MCAONS mice had significantly higher number of Bax
positive cells in brain tissue than MCAOG (P<0.05). The mean MDA level was
significantly lower (P<0.05) and the GSH-Px activity was significantly higher
(P<0.05) in brains of MCAOG mice compared to those of MCAONS mice.Conclusion GSPE
administration protects mice from ischemia-reperfusion brain injury through
attenuating oxidative stress and apoptosis, promoting angiogenesis, and
activating antioxidant enzyme GSH-Px. GSPE may represent a new therapeutical
direction for the treatment of ischemia-reperfusion brain injury.
PMID- 28693690
TI - Clinical Evaluation of Color Doppler Ultrasound in Selecting the Optimal
Treatment Modality for Infantile Hemangioma.
AB - Objective We investigated the efficacy and safety of 1064 nm Nd: YAG laser,
intense pulsed light (IPL), and lauromacrogol injection in the treatment of
hemangioma, in order to evaluate the value of color Doppler ultrasound guidance
in choosing the optimal treatment modality. Methods Infantile patients who were
clinical diagnosed as hemangiomas were randomly divided into group A, who had
color Doppler ultrasound examinations before the treatment, and group B who had
the treatment without ultrasound evaluation. Patients in the group A were
assigned into subgroups according to the depth of lesion by sonography: group A-1
for those who had a lesion depth <1.2 mm, and took intense pulsed light therapy;
group A-2 for those who had a lesion depth >=1.2mm and < 3 mm, and took long
pulse 1064 nm Nd:YAG laser therapy; group A-3 for those who had a lesion depth
>=3mm and <5 mm, and were treated by IPL combined with long pulse 1064 nm Nd:YAG
laser treatment; Group A-4 for those who had a lesion depth >=5 mm, and took
lauromacrogol injection therapy. Patients in the group B took long pulse 1064 nm
Nd:YAG laser treatment without preoperative ultrasound evaluation. The efficacy
and adverse reactions of the treatments between the groups were evaluated and
compared statistically.Results Totally 113 patients with 128 skin lesions were
enrolled in this study, 85 in the group A (mean age 6.8+/-7.9 months) and 28 in
the group B (mean age 6.9+/-9.9 months). The mean depth of hemangioma was 3.3+/
1.1 mm in the group A, ranging from 0.5-7.8 mm, with 0.8+/-0.4 mm, 2.2+/-0.4 mm,
4.2+/-0.6 mm and 6.2+/-0.7 mm in group A1, A2, A3 and A4, respectively. The cure
rates and effective rates in the group A were significantly higher than those in
the group B (cure rates: 64.5% vs 56.3%, U=3.378, P=0.045; effective rates: 89.5%
vs 78.1%, U=4.163, P=0.041). The adverse effect rates of the group A (vesicle
20.0%, pigmentation 46.9%, scarring 17.7%) were lower than those of the group B
(vesicle 21.9%, pigmentation 60.4%, scarring 25.0%). Incidences of pigmentation
and scarring were statistically significantly different (U=3.884, P=0.034, and
U=4.016, P=0.032 respectively) between the two groups.Conclusion With the
guidance of color Doppler ultrasound, the efficacy and safety of long pulse 1064
nmNd:YAG laser, intense pulsed light, and lauromacrogol injection in the
treatment of infantile hemangioma have better outcomes compared to laser
treatment alone without preoperative ultrasound examination.
PMID- 28693691
TI - Prevalence of Carbapenem-Resistant Klebsiella Pneumoniae (CRKP) and the
Distribution of Class 1 Integron in Their Strains Isolated from a Hospital in
Central China.
AB - Objective The aim of our study is to investigate the prevalence of Carbapenem
resistant Klebsiella pneumoniae (CRKP) and the genetic characteristics of the
class 1 integron in CRKP on multi-drug resistance.Methods Clinical Klebsiella
pneumoniae strains were collected from multiple departments of a hospital in
central China. CRKP strains were identified among the isolates, and antibiotics
susceptibility of CRKP strains was analyzed. The polymerase chain reaction (PCR)
was adopted to amplify the class 1 integron variable area. The integron genetic
structure was analyzed with enzyme digestion and DNA sequencing technology. The
relation between class 1 integron and drug resistance was analyzed
statistically.Results Totally 955 strains of Klebsiella pneumoniae were isolated
from varied sites of the hospital, and 117(12.3%) of them were identified as
CRKP, with a separation rate of 8.9% (26/292) in 2013, 11.3% (38/336) in 2014 and
16.2% (53/327) in 2015, which shows an increasing trend by year. 44.4% (52/117)
of CRKP strains were separated from specimen of ICU, and 61.5% (72/117) were from
sputum. Over 95% CRKP strains were resistant to ampicillin/sulbactam, aztreonam,
imipenem, meropenem, ceftazidme, cefotaxime, cefepime,and piperacillin, while
relatively low resistant rates were found in tigecycline (12.8%) and colistin
(35.9%). The class 1 integron was detected in 77.8% (91/117) of CRKP strains.
Class 1 integron of CRKP was significantly correlated with the antibiotic
resistance to the tobramycin, gentamicin and amikacin (all P<0.01). The gene
cassette analysis of variable area of class 1 integron showed that aadA2 accounts
for 64.8% (59/91), aacA4-catB8-aadA1 23.1% (21/91), and aadA2-dfrA25 12.1%
(11/91).Conclusions CRKP has an increasing trend in a clinical setting in China,
and most of them were resistant to multiple antibiotics. Class 1 integron in CRKP
has strong ability to capture the genes resistant to aminoglycosides antibiotics
from environment, with the aadA2 gene as the most popular one.
PMID- 28693692
TI - The Characteristics of Blood Supply and Tissue Hypoxia in Pathological Scars.
AB - Blood supply is believed to be an important aspect in the development of
pathological scars. However, there are controversies about vascular distribution,
vascular structure and blood flow in pathological scars. Additionally, hypoxic
microenvironment plays an important role in the vascularization of pathological
scar tissues, and hypoxic conditions can be reflected by metabolic indexes and
some cytokines. Furthermore, the correlation between blood supply and tissue
hypoxia is controversial. The aim of this article is to review the literature on
the characteristics of blood supply and tissue hypoxia in pathological scars,
from which we can see pathological scars have unique characteristics of blood
supply that are closely associated with tissue hypoxia. Moreover, development in
the treatment of pathological scars is herein reviewed.
PMID- 28693693
TI - Can Fundus Fluorescein Angiography be Performed for Diabetic Patients on Oral
Metformin?.
AB - Metformin is a kind of biguanide hypoglycemic agent that has been widely used in
patients with diabetes mellitus. In clinical practice, whether metformin should
be stopped before Fundus fluorescein angiography (FFA) remains largely unclear.
Some endocrinologists suggest stop metformin before FFA. However,
ophthalmologists do not always adopt this opinion in their practice. This
situation may lead to disputes between physicians and patients. This article
analyzed contrast-induced nephropathy(CIN) and the related contrast agent, as
well as the adverse reactions of fluorescein angiography. It pointed out that the
discrepancy may be caused by misunderstanding of contrast agents used in FFA. For
angiography using iodine contrast agent, metformin must be stopped because of the
increased possibility of CIN, while for FFA using fluorescein sodium, no CIN has
been reported yet. Therefore, the authors believe FFA is safe for diabetic
patients with oral metformin and it is unnecessary to stop metformin before the
examination.
PMID- 28693694
TI - Trigeminal Ganglioneuroma in the Middle-posterior Cranial Fossa: a Case Report.
PMID- 28693695
TI - Asymmetric Crying Facies with Multiple Congenital Malformations: a Case Report.
PMID- 28693696
TI - Intraoperative Right Ventricular Myocardial Infarction in a Geriatric Patient
with Hip Fracture: a Case Report.
PMID- 28693697
TI - [Therapeutic Residential Care for Children and Youth: A Consensus Statement of
the International Work Group on Therapeutic Residential Care].
AB - Therapeutic Residential Care for Children and Youth: A Consensus Statement of the
International Work Group on Therapeutic Residential Care. In many developed
countries around the world residential care interventions for children and
adolescents have come under increasing scrutiny. Against this background an
international summit was organised in England (spring 2016) with experts from 13
countries to reflect on therapeutic residential care (TRC). The following working
definition of TRC was leading: “Therapeutic residential care involves the
planful use of a purposefully constructed, multi-dimensional living environment
designed to enhance or provide treatment, education, socialization, support, and
protection to children and youth with identified mental health or behavioral
needs in partnership with their families and in collaboration with a full
spectrum of community based formal and informal helping resources”. The
meeting was characterised by exchange of information and evidence, and by
preparing an international research agenda. In addition, the outlines of a
consensus statement on TRC were discussed. This statement, originally published
in English and now reproduced in a Spanish translation, comprises inter alia five
basic principles of care that according to the Work Group on Therapeutic
Residental Care should be guiding for residential youth care provided at any
time.
PMID- 28693698
TI - Meta-analysis of family-based selective prevention programs for drug consumption
in adolescence.
AB - BACKGROUND: Substance consumption (SC) begins in adolescence and has been linked
to protection factors such as family relationships (FR) and positive parenting
(PP). There are few studies concerning the effectiveness of prevention programs
based on the family, even though assessing interventions is one of the objectives
of preventive science. The aim of this study was to analyze the evidence on
family-based selective prevention programs in relation to drug consumption in
adolescents. METHODOLOGY: A meta-analysis of 9 studies with 102 measures grouped
in three dimensions, FR, PP and SC, ranging between 2001 and 2015, was conducted.
RESULTS: Effect sizes (ES) were found to be 0.82 for FR, 0.71 for PP, 0.77 for
the combination of both and 0.21 for SC. The Q and I2 indexes expressed high
heterogeneity. CONCLUSIONS: Despite obtaining high ES consistent with previous
studies, the great heterogeneity found did not allow us to draw clear conclusions
regarding the primary studies. It is recommended that methodological improvements
in assessment and reporting processes be carried out for future comparisons.
PMID- 28693699
TI - Volunteer Functions Inventory: A systematic review.
AB - The objective of this research study was to conduct a systematic review of the
research on volunteers using Clary et al.’s VFI (1998). A total of 48
research studies including 67 independent samples met eligibility criteria. The
total sample of the studies analyzed ranged from 20375 to 21988 participants,
depending on the motivation analyzed. The results show that the Values factor
obtained the highest mean score, both overall and in each type of volunteering,
whereas the lowest scores were for the Career and Enhancement factors. Studies
conducted with samples with a mean age under 40 years obtain higher scores on
Career and Understanding scales when compared to studies in older samples. The
group of studies with less than 50% women yield higher mean scores on the Social
scale than studies with more than 50% women in the sample. All the scales show
reliability coefficients between .78 and .84. Only eight of the articles provide
data on the reliability of the scale with a mean value of .90. Of the 26 studies
that performed factor analysis, 18 confirmed the original structure of six
factors.
PMID- 28693700
TI - Longitudinal effects of an intervention on perfectionism in adolescents.
AB - : Perfectionism is a personality disposition characterized by a person´s
striving for flawlessness and the setting of excessively high performance
standards. This trait has been associated with a broad range of
psychopathological conditions. Consequently, prevention of its harmful effects
must start early. OBJECTIVE: To investigate if one group session to manage
perfectionism has the effect of reducing the levels of this trait, two and six
months later. METHOD: A community-based sample of 978 Portuguese adolescents from
three different high schools completed a self-reporting questionnaire including
the Child and Adolescent Perfectionism Scale, before and after one skill session.
Three groups were formed: the intervention group received a skill session aimed
at reducing perfectionism; control group 1 received a skill session aimed at
healthy habits, and control group 2 received no intervention. RESULTS: At
baseline, no significant mean differences were found by gender or by school in
Total Perfectionism or its dimensions. After one session to manage Perfectionism,
the intervention group showed significant reduction in self-oriented
perfectionism (SOP) scores, two months (p = .001) and six months later (p = .02).
No significant reductions were observed in the control groups. DISCUSSION: Our
findings suggest that adolescents are sensitive to short interventions aimed at
reducing perfectionism.
PMID- 28693701
TI - The role of hopelessness and meaning in life in a clinical sample with non
suicidal self-injury and suicide attempts.
AB - BACKGROUND: Non-suicidal self-injury (NSSI) and suicide attempts (SA) lie on a
continuum of self-harm, and literature has shown that patients with suicidal
intent constitute a more severe group. METHOD: This study aimed to explore
differences in the facets of hopelessness (Beck Hopelessness Scale) and meaning
in life (Purpose in Life Test) in a clinical sample of 150 patients with a
diagnosis of a mental disorder with: a) no NSSI/SA, b) only NSSI, or c) SA/NSSI
and SA. RESULTS: The results showed statistically significant differences between
the groups in the affective dimension, but they showed similar levels of meaning
in life in both groups. CONCLUSION: These findings highlight that affective
hopelessness can lead to suicide attempts, and that meaning in life underlies the
continuum of self-harm. Implications for psychotherapeutic interventions are
discussed.
PMID- 28693702
TI - The HIDEA School-Based Screening Scale for Teachers to Detect ADHD Markers in
Elementary Students.
AB - BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is associated with
academic difficulties both short- and long-term. The aim of the study was to
provide a new brief ADHD screening scale that could be easily used by teachers
and educational professionals in elementary schools. METHOD: Participants were
teachers of 158 children with a prior diagnosis of ADHD and 169 children without
a diagnosis of ADHD. An initial pool of 38 items was generated from ADHD symptoms
of both DSM-5 and CIE-10 criteria, as well from Conners 3, EDAH, SDQ and ADHD-RS
IV scales. RESULTS: A 5-item model showed the best fit (c2 = 7.04; d.f. = 5; p =
.218; RMSEA = .035; CFI = .999; TLI = .999). The HIDEA total score was highly
correlated with both ADHD-IN (r = .93; p<.001) and ADHD-HY (r = .87; p<.001). The
ROC curve for the HIDEA total score gave an AUC value of .998 (95%, CI = [.994,
1.000]). HIDEA scale showed a good sensitivity (97%) and very good specificity
(3%). CONCLUSION: The HIDEA scale has shown adequate psychometric properties. It
is potentially useful for screening ADHD in elementary grade as part of a
preventive strategies in school settings.
PMID- 28693703
TI - Stress, competence, and parental educational styles in victims and aggressors of
bullying and cyberbullying.
AB - BACKGROUND: The family can be a protective/risk factor for violence. The study
analyzes differences in family variables (parental stress, parental competence
and parenting styles) among severe student victims, aggressors, cybervictims, and
cyberaggressors (who have very frequently suffered or carried out
bullying/cyberbullying behaviors in the past year) and those who have neither
suffered nor carried out any aggressive behavior or only occasionally. METHOD:
Participants were 1,993 students in the 5th-6th grade (9-13 years old). RESULTS:
Victims and aggressors of bullying had parents with higher levels of parental
stress, who used more authoritarian educational styles (low affection, coercive
discipline, high control), and more permissive practices (high
affection/overprotection, low demand/control); parents of aggressors also had a
lower level of parental competence. Cybervictims had parents with higher parental
stress who used more permissive educational styles. Cyberaggressors had parents
with a low level of parental competence. CONCLUSIONS: The family context is
relevant for bullying/cyberbullying, but family variables have more influence on
bullying than on cyberbullying.
PMID- 28693704
TI - The role of self-referencing in true and false recognition in young people and
healthy older people.
AB - BACKGROUND: Given the uneven results about the role self-referencing plays in
false recognition, we planned an experiment that would allow us to analyze
whether self-referencing affects false recognition, and its relationship with
healthy aging. METHOD: A sample of healthy older people (n = 30) and another
sample of young people (n = 38) rated whether 40 personality-trait adjectives (20
with a positive valence and 20 with a negative valence) described them or not
(self-referencing condition). They then took a recognition test of these
adjectives along with 40 other new adjectives. Next, they rated whether 40 other
different adjectives described a third person or not (other-referencing
condition), and then performed another similar recognition test. These two
conditions were counter-balanced across participants. RESULTS: The results
clearly showed that self-referencing produces both an increase in true
recognition and a decrease in false recognition in both samples. CONCLUSIONS: Our
results support the idea that self-referencing reduces false recognition by using
conscious monitoring strategies, and that self-referencing is a suitable
cognitive method for enhancing older individuals’ impaired memory.
PMID- 28693705
TI - Effects of temporal contexts and contextual habituation on latent inhibition.
AB - BACKGROUND: Latent inhibition of conditioned taste aversion (CTA) is sensitive to
external and internal cues. Time of day can serve as an internal cue, and latent
inhibition may be reduced if the pre-exposure and conditioning stages occur at
different times of day. This contextual cue attributed to a change in the time of
day may reveal a temporal specificity of latent inhibition. Although the
habituation period to spatial contexts is a determinant variable for the spatial
specificity of latent inhibition of CTA, the influence of contextual-temporal
familiarity (time of day) on latent inhibition of CTA has not been explored
through direct comparisons between different periods of habituation to the
temporal context. METHOD: Two different periods of contextual habituation (short
vs. long) previous to taste pre-exposures were compared in Wistar rats to analyze
the influence of these periods on the temporal specificity of latent inhibition
of CTA. RESULTS: A long period of habituation, in relation to a short period,
facilitated the effect of a change of the time of day between pre-exposure and
conditioning on the magnitude of taste aversion. CONCLUSIONS: A long habituation
to temporal contexts facilitates the temporal specificity of latent inhibition of
CTA.
PMID- 28693706
TI - Cognitive techniques and language: A return to behavioral origins.
AB - BACKGROUND: the main purpose of this study is to offer an alternative explanatory
account of the functioning of cognitive techniques that is based on the
principles of associative learning and highlights their verbal nature. The
traditional accounts are questioned and analyzed in the light of the situation of
psychology in the 1970s. METHOD: conceptual analysis is employed to revise the
concepts of language, cognition and behavior. Several operant- and Pavlovian
based approaches to these phenomena are presented, while particular emphasis is
given to Mowrer’s (1954) approach and Ryle (1949) and Wittgenstein’s
(1953) philosophical contributions to the field. CONCLUSIONS: several logical
problems are found in regard to the theoretical foundations of cognitive
techniques. A combination of both operant and Pavlovian paradigms based on the
above-mentioned approaches is offered as an alternative explanatory account of
cognitive techniques. This new approach could overcome the conceptual fragilities
of the cognitive standpoint and its dependence upon constructs of dubious logical
and scientific validity.
PMID- 28693707
TI - The role of backward associative strength in false recognition of DRM lists with
multiple critical words.
AB - BACKGROUND: Memory is a reconstruction of the past and is prone to errors. One of
the most widely-used paradigms to examine false memory is the Deese/Roediger
McDermott (DRM) paradigm. In this paradigm, participants studied words
associatively related to a non-presented critical word. In a subsequent memory
test critical words are often falsely recalled and/or recognized. METHOD: In the
present study, we examined the influence of backward associative strength (BAS)
on false recognition using DRM lists with multiple critical words. In forty-eight
English DRM lists, we manipulated BAS while controlling forward associative
strength (FAS). Lists included four words (e.g., prison, convict, suspect,
fugitive) simultaneously associated with two critical words (e.g., CRIMINAL,
JAIL). RESULTS: The results indicated that true recognition was similar in high
BAS and low-BAS lists, while false recognition was greater in high-BAS lists than
in low-BAS lists. Furthermore, there was a positive correlation between false
recognition and the probability of a resonant connection between the studied
words and their associates. CONCLUSIONS: These findings suggest that BAS and
resonant connections influence false recognition, and extend prior research using
DRM lists associated with a single critical word to studies of DRM lists
associated with multiple critical words.
PMID- 28693708
TI - Affective and physiological correlates of the perception of unimodal and bimodal
emotional stimuli.
AB - BACKGROUND: Despite the multisensory nature of perception, previous research on
emotions has been focused on unimodal emotional cues with visual stimuli. To the
best of our knowledge, there is no evidence on the extent to which incongruent
emotional cues from visual and auditory sensory channels affect pupil size. AIMS:
To investigate the effects of audiovisual emotional information perception on the
physiological and affective response, but also to determine the impact of
mismatched cues in emotional perception on these physiological indexes. METHOD:
Pupil size, electrodermal activity and affective subjective responses were
recorded while 30 participants were exposed to visual and auditory stimuli with
varied emotional content in three different experimental conditions: pictures and
sounds presented alone (unimodal), emotionally matched audio-visual stimuli
(bimodal congruent) and emotionally mismatched audio-visual stimuli (bimodal
incongruent). RESULTS: The data revealed no effect of emotional incongruence on
physiological and affective responses. On the other hand, pupil size covaried
with skin conductance response (SCR), but the subjective experience was partially
dissociated from autonomic responses. CONCLUSION: Emotional stimuli are able to
trigger physiological responses regardless of valence, sensory modality or level
of emotional congruence.
PMID- 28693709
TI - The effect of interpersonal relationships on burnout syndrome in Secondary
Education teachers.
AB - BACKGROUND: Recent studies show that teachers, especially in Secondary Education
present varying levels of burnout syndrome. This problem could be caused by
internal factors unique to the subject (psychological characteristics) or
external factors (overwork, social climate, etc.). METHOD: The objective of this
study is to analyze the influence of interpersonal relationships on the
development of burnout in a sample of 794 secondary education teachers from the
Community of Madrid, applying structural equation modeling methodology. RESULTS:
it was observed that the teacher-student relationship has a significant effect on
each of the three dimensions of the syndrome (exhaustion, cynicism, and
inefficacy), and the teacher-superiors and teacher-coworker relationships show a
moderate effect on these dimensions. CONCLUSIONS: The results show the importance
of taking care of interpersonal relationships in schools to ensure the well-being
of teachers and, ultimately, the quality of the learning process.
PMID- 28693710
TI - Lifetime victimization among Spanish adolescents.
AB - BACKGROUND: The damaging effects of direct and indirect experience of
interpersonal violence on children’s development are widely acknowledged.
The objective of the present study was to analyze lifetime victimization among
adolescents of a community sample. METHOD: Participants were 608 adolescents aged
12-18 from Northern Spain. The Juvenile Victimization Questionnaire was used to
measure lifetime victimization. RESULTS: Over 90% of the adolescent population
has been exposed to some kind of victimization. Participants reported an average
of 5.50 lifetime victimization experiences and 75% of the sample reported the
experience of at least two forms of victimization. The 10% most victimized part
of the sample, participants reporting 11 or more victimizations, were classified
as polyvictims. CONCLUSIONS: Victimization is very frequent even among community
adolescents, especially peer victimization and witnessing community violence.
PMID- 28693711
TI - Comparison of methods for dealing with missing values in the EPV-R.
AB - BACKGROUND: The development of an effective instrument to assess the risk of
partner violence is a topic of great social relevance. This study evaluates the
scale of “Predicción del Riesgo de Violencia Grave Contra la
Pareja” –Revisada– (EPV-R - Severe Intimate Partner Violence
Risk Prediction Scale-Revised), a tool developed in Spain, which is facing the
problem of how to treat the high rate of missing values, as is usual in this type
of scale. METHOD: First, responses to the EPV-R in a sample of 1215 male abusers
who were reported to the police were used to analyze the patterns of occurrence
of missing values, as well as the factor structure. Second, we analyzed the
performance of various imputation methods using simulated data that emulates the
missing data mechanism found in the empirical database. RESULTS: The imputation
procedure originally proposed by the authors of the scale provides acceptable
results, although the application of a method based on the Item Response Theory
could provide greater accuracy and offers some additional advantages.
CONCLUSIONS: Item Response Theory appears to be a useful tool for imputing
missing data in this type of questionnaire.
PMID- 28693712
TI - Calibrating a new item pool to adaptively assess the Big Five.
AB - BACKGROUND: Even though the Five Factor Model (FFM) has been the dominant
paradigm in personality research for the past two decades, very few studies have
measured the FFM adaptively. Thus, the purpose of this research was the building
of a new item pool to develop a computerized adaptive test (CAT) for personality
assessment. METHOD: A pool of 480 items that measured the FFM facets was
developed and applied to 826 participants. Facets were calibrated separately and
item selection was performed being mindful of the preservation of
unidimensionality of each facet. Then, a post-hoc simulation study was carried
out to test the performance of separate CATs to measure the facets. RESULTS: The
final item pool was composed of 360 items with good psychometric properties.
Findings reveal that a CAT administration of four items per facet (total length
of 120 items) provides accurate facets scores, while maintaining the factor
structure of the FFM. CONCLUSIONS: An item pool with good psychometric properties
was obtained and a CAT simulation study demonstrated that the FFM facets could be
measured with precision using a third of the items in the pool.
PMID- 28693713
TI - Rationale and Applicability of Exploratory Structural Equation Modeling (ESEM) in
psychoeducational contexts.
AB - BACKGROUND: In last few years, the use of confirmatory factor analysis (CFA) has
become dominant in structural validation of psychological tests. However, the
requirement of latent variables only loading on specific target items introduces
some constraints on the solutions found, namely a factor solution that links some
items only in one specific dimension. The most recent use of exploratory
structural equation modeling (ESEM), which allows items to be predominantly
related to a factor, with non-zero loadings on other factors, has been identified
as the one that best respects the proper functioning of the assessed
psychological attributes. METHOD: In this study we compared the two approaches to
structural validity using the answers of a sample of 2,478 first-year higher
education students to a multidimensional questionnaire of academic expectations.
RESULTS: The results show clear gains in information collected when combining CFA
and ESEM. CONCLUSIONS: In conclusion, some implications are highlighted for
research and practice of psychological assessment.
PMID- 28693714
TI - Psychometric properties of the Spanish version of the Anxiety Sensitivity Index
for Children.
AB - BACKGROUND: Anxiety sensitivity is a useful construct in explaining anxiety
disorders. The Anxiety Sensitivity Index for Children (ASIC) is a brief self
report designed to assess anxiety sensitivity in youth. METHOD: Students (N =
1348; ages 10-17) completed a Spanish translation of the ASIC and measures of
anxiety and depression. RESULTS: Confirmatory factor analyses found that scores
on the ASIC- Spanish version can be fitted to two factorial structures: A single
factor and two first-order factors grouped into one higher-order factor. The two
factor structure was invariant between children and adolescents, and between boys
and girls. The ASIC scales (Total Score, Mental Concerns, and Physical Concerns)
demonstrated high internal consistency and test-retest reliability. ASIC scores
were significantly related to measures of anxiety and, to a lesser extent, to a
measure of depression. CONCLUSIONS: Results supported the factorial, convergent,
and discriminant validity of ASIC scores in Spanish youth.
PMID- 28693715
TI - Spanish adaptation of the Patient Health Engagement scale (S.PHE-s)in patients
with chronic diseases.
AB - BACKGROUND: The Patient Health Engagement scale is an instrument based on
evidence about the experiences and preferences of patients with chronic diseases
regarding their engagement with the treatment they receive. AIMS: The main goal
of this study was to adapt the Patient Health Engagement scale to the Spanish
population (S.PHE-s) following the guidelines for cross-cultural adaptations.
METHODS: The sample comprised 413 patients with different chronic diseases.
RESULTS: The confirmatory factor analysis showed a one factor model corresponding
to the structure proposed by the original authors. The factor structure was
invariant by gender. Furthermore, a Rasch Model showed that the S.PHE-s was
unidimensional. In addition, every polychoric correlation coefficient was higher
than .60. The Ordinal Alpha of the S.PHE-s was .85. Finally, the S.PHE-s was
found to be positively related to life satisfaction, positive affect, and
treatment adherence and negatively correlated to negative affect, depression, and
anxiety. CONCLUSIONS: In light of these results, it may be concluded that the
S.PHE-s has good psychometric properties and it may be used by the Spanish
speaking scientific community to measure patient engagement.
PMID- 28693716
TI - Psychometric Properties of the Spanish version of the Family Adaptability and
Cohesion Evaluation Scale IV.
AB - INTRODUCTION: Building on the expanding cross cultural interest in FACES, the
Spanish version of the Family Adaptability and Cohesion Evaluation Scale (FACES
IV), aimed at the assessment of the dimensions of cohesion and flexibility of the
Circumplex Model, was validated following the author´s guidelines. METHOD:
The sample was composed by 665 college students. Besides, FACES II was also used
and family communication, satisfaction, stress and strengths were also measured.
RESULTS: The results supported its psychometric adequacy. Construct validity,
concurrent and discriminant validity of all the scales were confirmed,
maintaining the original structure of the instrument, with 6 scales, 4 Unbalanced
scales (Disengaged, Enmeshed, Rigid, and Chaotic), and two Balanced scales
(Cohesion and Flexibility). Additionally, the ratio scores confirmed the
curvilinearity of the model. CONCLUSION: All the results supported the adequacy
of the Spanish version, which is also promising for use in educational settings,
in counseling and in research. Findings with the Spanish version of FACES IV are
similar to findings in the United States and other countries.
PMID- 28693717
TI - Psychometric properties of the spanish version of The Distress Tolerance Scale
and its relationship with personality and psychopathological symptoms.
AB - BACKGROUND: Distress tolerance is defined as the individual’s capacity to
experience and withstand negative psychological states. The goal of this study
was to examine the psychometric properties and the factor structure of the
Spanish version of the Distress Tolerance Scale (DTS) and to test its
relationship with psychopathological symptoms and personality. METHOD: A sample
of 650 participants completed the DTS, the Eysenck Personality Questionnaire
Revised–Abbreviated) (EPQR-A), and the Symptom Assessment-45 Questionnaire
(SA-45). RESULTS: The DTS showed good internal consistency (Cronbach’s
alpha) and adequate temporal stability (7-month test-retest). Results of a
confirmatory factor analysis supported the hypothesized 4-factor structure
(tolerance, appraisal, absorption, and regulation) that load onto a higher-order
general factor. A structural equation model (SEM) was tested to provide evidence
of construct validity. Neuroticism was inversely associated with distress
tolerance, and distress tolerance partially mediated the effects of neuroticism
on current symptoms. Results indicated that the Spanish DTS mediated associations
between personality traits and current psychiatric symptoms. CONCLUSIONS: Results
support the use of this version as a useful tool for assessing distress tolerance
in clinical and research settings in Spanish-speaking countries. In addition, we
found that distress tolerance may form a link between neuroticism and
psychopathology.
PMID- 28693718
TI - Partners in Recovery program evaluation: changes in unmet needs and recovery.
AB - Objective Partners in Recovery (PIR) is an Australian government initiative
designed to provide support and service linkage for individuals with complex
needs living with severe and persistent mental illness. The aim of the present
study was to examine whether consumers engaged in PIR programs in two large
regions of Sydney experienced: (1) a reduction in unmet needs (either via self-
or staff report); and (2) progress in their self-reported mental health
recovery.Methods Unmet needs were measured using the Camberwell Assessment of
Need Short Appraisal Scale and recovery was measured using the Recovery
Assessment Scale - Domains and Stages. For individuals with initial and follow-up
data, paired t-tests were used to examine change over time.Results At follow-up,
individuals reported an average of two to three fewer unmet needs, and recovery
scores increased by approximately 5% across each domain and the total score. At
follow-up, the most common unmet needs were in the areas of 'company' and
'daytime activities'.Conclusions The results of the present study suggest that
PIR services in these two geographical regions have achieved positive results.
Individuals with severe and persistent mental illness engaged with PIR appear to
have reduced their unmet needs and enhanced their mental health recovery.What is
known about the topic? PIR services were established to support individuals with
severe and persistent mental illness by creating service linkages to address
unmet needs in order to facilitate recovery. Services were delivered through the
new role of 'support facilitator'.What does this paper add? By examining
routinely collected outcome measures, this paper shows the success of the PIR
program. Individuals engaged with PIR reported fewer unmet needs and enhanced
recovery over the time they were involved with the program. However, they still
faced serious challenges in building successful social interactions, such as
developing friendships, and participating in meaningful activities.What are the
implications for practitioners? The support facilitator role developed as part of
PIR appears to be a useful method of supporting individuals to reduce unmet needs
and enhance recovery. However, further work is required to address the challenges
associated with overcoming social isolation and participation in meaningful
activities.
PMID- 28693719
TI - Type XVII collagen coordinates proliferation in the interfollicular epidermis.
AB - Type XVII collagen (COL17) is a transmembrane protein located at the epidermal
basement membrane zone. COL17 deficiency results in premature hair aging
phenotypes and in junctional epidermolysis bullosa. Here, we show that COL17
plays a central role in regulating interfollicular epidermis (IFE) proliferation.
Loss of COL17 leads to transient IFE hypertrophy in neonatal mice owing to
aberrant Wnt signaling. The replenishment of COL17 in the neonatal epidermis of
COL17-null mice reverses the proliferative IFE phenotype and the altered Wnt
signaling. Physical aging abolishes membranous COL17 in IFE basal cells because
of inactive atypical protein kinase C signaling and also induces epidermal
hyperproliferation. The overexpression of human COL17 in aged mouse epidermis
suppresses IFE hypertrophy. These findings demonstrate that COL17 governs IFE
proliferation of neonatal and aged skin in distinct ways. Our study indicates
that COL17 could be an important target of anti-aging strategies in the skin.
PMID- 28693720
TI - Individual recognition and the 'face inversion effect' in medaka fish (Oryzias
latipes).
AB - Individual recognition (IR) is essential for maintaining various social
interactions in a group, and face recognition is one of the most specialised
cognitive abilities in IR. We used both a mating preference system and an
electric shock conditioning experiment to test IR ability in medaka, and found
that signals near the face are important. Medaka required more time to
discriminate vertically inverted faces, but not horizontally shifted faces or
inverted non-face objects. The ability may be comparable to the classic 'face
inversion effect' in humans and some other mammals. Extra patterns added to the
face also did not influence the IR. These findings suggest the possibility that
the process of face recognition may differ from that used for other objects. The
complex form of recognition may promote specific processing adaptations, although
the mechanisms and neurological bases might differ in mammals and medaka. The
ability to recognise other individuals is important for shaping animal societies.
PMID- 28693722
TI - Safety assessment of passing relief lanes using microsimulation-based conflicts
analysis.
AB - The paper target is to analyze the influence of passing lane section and merging
area lengths, which represent a critical part in the geometric design of passing
lanes. The lack of observed data and the still limited implementation of short
passing 2+1 lane in Poland do not allow to perform a reliable performance-based
design of their length to balance context and economical restrains with
operational and safety performances. Besides, defining the optimum geometric
design from observed data is a reactive approach which require detailed
observations and evaluations of the safety and operational performances for
different geometric configurations. The present research work aims to fill the
gap by performing an evaluation of optimal length, based on microsimulation
analysis. Particular attention was paid to the calibration and validation of
microsimulation models using real data of traffic characteristics and crash
history. The assessment was conducted using simulation models in VISSIM and
Surrogate Safety Assessment Model (SSAM) software and comparison based on
simulated results at different lengths of passing lane, merging area in a wide
range of AADT values. The results suggested not only that conflicts can be a
surrogate measure of safety but also that the influence of geometric parameter,
such as the length of the additional lane, plays a fundamental role in the safety
performance of the 2+1 short passing lane.
PMID- 28693721
TI - Mitosis can drive cell cannibalism through entosis.
AB - Entosis is a form of epithelial cell cannibalism that is prevalent in human
cancer, typically triggered by loss of matrix adhesion. Here, we report an
alternative mechanism for entosis in human epithelial cells, driven by mitosis.
Mitotic entosis is regulated by Cdc42, which controls mitotic morphology. Cdc42
depletion enhances mitotic deadhesion and rounding, and these biophysical
changes, which depend on RhoA activation and are phenocopied by Rap1 inhibition,
permit subsequent entosis. Mitotic entosis occurs constitutively in some human
cancer cell lines and mitotic index correlates with cell cannibalism in primary
human breast tumours. Adherent, wild-type cells can act efficiently as entotic
hosts, suggesting that normal epithelia may engulf and kill aberrantly dividing
neighbours. Finally, we report that Paclitaxel/taxol promotes mitotic rounding
and subsequent entosis, revealing an unconventional activity of this drug.
Together, our data uncover an intriguing link between cell division and
cannibalism, of significance to both cancer and chemotherapy.
PMID- 28693723
TI - Determination of formylated DNA and RNA by chemical labeling combined with mass
spectrometry analysis.
AB - Nucleic acids carry diverse chemical modifications that exert critical influences
in a variety of cellular processes in living organisms. In addition to
methylation, the emerging DNA and RNA formylation has been reported to play
functional roles in various physiological processes. However, the amounts of
formylated DNA and RNA are extremely low and detection of DNA and RNA formylation
is therefore a challenging task. To address this issue, we developed a strategy
by chemical labeling combined with in-tube solid-phase microextraction - ultra
high performance liquid chromatography - electrospray ionization - tandem mass
spectrometry (in-tube SPME-UPLC-ESI-MS/MS) analysis for the sensitive
determination of DNA and RNA formylation. Using the developed method, we were
able to simultaneously measure six formylated nucleosides, including 5-formyl-2'
deoxycytidine (5-fodC), 5-formylcytidine (5-forC), 5-formyl-2'-deoxyuridine (5
fodU), 5-formyluridine (5-forU), 2'-O-methyl-5-formylcytidine (5-forCm) and 2'-O
methyl-5- formyluridine (5-forUm), from DNA and RNA of cultured human cells and
multiple mammalian tissues. The detection limits of these formylated nucleosides
improved by 307-884 folds using Girard's P (GirP) labeling coupled with in-tube
SPME-UPLC-ESI-MS/MS analysis. It was worth noting that 5-forU, 5-forCm and 5
forUm which have not been detected in human sample before, were discovered in
cultured human cells and tissues in the current study. In addition, we observed
significant increase of 5-forC and 5-forU in RNA (p = 0.027 for 5-forC; p = 0.028
for 5-forU) and 5-fodU in DNA (p = 0.002) in human thyroid carcinoma tissues
compared to normal tissues adjacent to the tumor using synthesized stable isotope
GirP (d5-GirP)-assisted quantification. Our results indicated that aberrant DNA
and RNA formylation may contribute to the tumor formation and development. In
addition, monitoring of DNA and RNA formylation may also serve as indicator for
cancer diagnostics. Taken together, the developed chemical labeling combined with
in-tube SPME-UPLC-ESI-MS/MS analysis can facilitate the in-depth functional study
of DNA and RNA formylation.
PMID- 28693724
TI - Direct coupling of supercritical fluid chromatography with tandem mass
spectrometry for the analysis of amino acids and related compounds: Comparing
electrospray ionization and atmospheric pressure chemical ionization.
AB - For acceptance of supercritical fluid chromatography (SFC) as a routine analysis
method, the hyphenation to mass spectrometry (MS), which is typically achieved
either by a splitting device or by the employment of an additional make up flow,
has to be improved. Direct coupling of SFC to MS (/MS) would simplify the
handling of this method. Consequently, this work focused on the direct coupling
of SFC to mass spectrometry and the influence of the employed ion source on
signal intensities of polar and ionic compounds in biological samples. A method
for separating metabolites of the tryptophan pathway as well as other amino acids
is shown. Results demonstrate that SFC is capable of separating analytes of polar
and ionic nature. Modifications of the SFC system by cryostat cooling lead to
higher temperature stability in the booster pump and therefore to a better
reproducibility of retention times and a low dispersion nozzle inside the active
back pressure regulator (ABPR) significantly improves peak shape and sensitivity
when using the MS. The comparison of the ionization efficiencies using
electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI)
in positive and negative ion mode shows analyte depending sensitivities. However,
results indicate that APCI is better suitable for the ionization of amino acids
with polar side chains, whereas ESI proved superior for the ionization of amino
acids featuring hydrophobic residues. Analyte signals were suppressed with ESI
when using a complex matrix such as human serum, but rather enhanced when using
APCI.
PMID- 28693725
TI - Impact of gamma-irradiation, ageing and their interactions on multilayer films
followed by AComDim.
AB - To highlight the main factors involved in the degradation of polymers in
multilayer films under gamma-irradiation, the ANOVA Common Dimensions (AComDim,
Analysis of Variance in Common Dimensions) method is applied on spectra recorded
with ATR-FTIR (Attenuated Total Reflection-Fourier Transform Infrared). The
present study focuses on the stability of gamma-irradiated polymers used in
single-use plastic bags made of multilayer films for the biopharmaceutical and
biotechnological industries. The samples are irradiated at several gamma-doses,
up to 270 kGy, and compared with a non-irradiated sample used as reference. It
shows that the gamma-dose, the natural ageing up to six months and the gamma-dose
* ageing interaction are the most influential factors.
PMID- 28693726
TI - Point-of-need simultaneous electrochemical detection of lead and cadmium using
low-cost stencil-printed transparency electrodes.
AB - In this work, we report a simple and yet efficient stencil-printed
electrochemical platform that can be integrated into the caps of sample
containers and thus, allows in-field quantification of Cd(II) and Pb(II) in river
water samples. The device exploits the low-cost features of carbon (as electrode
material) and paper/polyester transparency sheets (as substrate). Electrochemical
analysis of the working electrodes prepared on different substrates (polyester
transparency sheets, chromatographic, tracing and office papers) with
hexaammineruthenium(III) showed that their electroactive area and electron
transfer kinetics are highly affected by the porosity of the material. Electrodes
prepared on transparency substrates showed the best electroanalytical performance
for the simultaneous determination of Cd(II) and Pb(II) by square-wave anodic
stripping voltammetry. Interestingly, the temperature and time at which the
carbon ink was cured had significant effect on the electrochemical response,
especially the capacitive current. The amount of Cd and Pb on the electrode
surface can be increased about 20% by in situ electrodeposition of bismuth. The
electrochemical platform showed a linear range comprised between 1 and 200 MUg/L
for both metals, sensitivity of analysis of 0.22 and 0.087 MUA/ppb and limits of
detection of 0.2 and 0.3 MUg/L for Cd(II) and Pb(II), respectively. The analysis
of river water samples was done directly in the container where the sample was
collected, which simplifies the procedure and approaches field analysis. The
developed point-of-need detection system allowed simultaneous determination of
Cd(II) and Pb(II) in those samples using the standard addition method with
precise and accurate results.
PMID- 28693727
TI - One-step synthesis of functional pNR/rGO composite as a building block for
enhanced ascorbic acid biosensing.
AB - An electrochemical sensor for ascorbic acid (AA) was prepared via an one-step
electrochemical approach by reducing graphene oxide (rGO) and co-polymerizing
neutral red (NR) and rGO to form a pNR/rGO hybrid film on the glassy carbon
electrode (pNR/rGO-GCE). Structures and properties of the obtained pNR/rGO film
were characterized by X-ray diffraction (XRD), X-ray photoelectron spectroscopy
(XPS), Fourier transform infrared (FT-IR) and UV-vis techniques. A significant
decrease of charge-transfer resistance (Rct) from over 20,000 Omega for pNR-GCE
to 130 Omega for pNR/rGO-GCE was validated by electrochemical impedance
spectroscopy (EIS) measurement. Particularly, electrochemical data revealed that
pNR/rGO film could effectively enhance the electron transfer between AA and
electrode, and thus reduce the overpotential of AA oxidation. Two linear
regression areas with 0.05-0.75 mM and 0.9-24.9 mM, detection limit with 1.4 MUM,
and stability over 2 weeks were obtained. The coexisting distractions such as
dopamine, uric acid and glucose were detected and eliminated. Moreover, the
pNR/rGO-GCE gave the same determination results as that obtained with HPLC when
measuring real samples, including vitamin C beverage and human serum.
PMID- 28693728
TI - Electrochemical detection of cardiac biomarker myoglobin using polyphenol as
imprinted polymer receptor.
AB - An electrochemical biosensor was developed by merging the features of Molecular
Imprinting technique and Screen-Printed Electrode (SPE) for the simple and fast
screening of cardiac biomarker myoglobin (Myo) in point-of-care (POC). The MIP
artificial receptor for Myo was prepared by electrooxidative polymerization of
phenol (Ph) on a AuSPE in the presence of Myo as template molecule. The choice of
the most effective protein extraction procedure from the various extraction
methods tested (mildly acidic/basic solutions, pure/mixed organic solvents,
solutions containing surfactants and enzymatic digestion methods), and the
optimization of the thickness of the polymer film was carefully undertaken in
order to improve binding characteristics of Myo to the imprinted polymer receptor
and increase the sensitivity of the MIP biosensor. The film thickness was
optimized by adjusting scan rate and the number of cycles during cyclic
voltammetric electropolymerization of Ph. The thickness of the polyphenol
nanocoating of only few nanometres (~4.4 nm), and similar to the protein
diameter, brought in significant improvements in terms of sensor sensitivity. The
binding affinity of MIP receptor film was estimated by fitting the experimental
data to Freundlich isotherm and a ~8 fold increase in the binding affinity of Myo
to the imprinted polymer (KF = 0.119 +/- 0.002 ng-1 mL) when compared to the non
imprinted polymer (KF = 0.015 +/- 0.002 ng-1 mL) which demonstrated excellent
(re)binding affinity for the imprinted protein. The incubation of the Myo MIP
receptor modified electrode with increasing concentration of protein (from 0.001
ng mL-1 to 100 MUg mL-1) resulted in a decrease of the ferro/ferricyanide redox
current. LODs of 2.1 and 14 pg mL-1 were obtained from calibration curves built
in neutral buffer and diluted artificial serum, respectively, using SWV
technique, enabling the detection of the protein biomarker at clinically relevant
levels. The prepared MIP biosensor was applied to the determination of Myo spiked
serum samples with satisfactory results.
PMID- 28693729
TI - Sialic acid linkage-specific permethylation for improved profiling of protein
glycosylation by MALDI-TOF MS.
AB - Protein glycosylation mediates a wide range of cellular processes, affecting
development and disease in mammals. Deciphering the "glycocodes" requires rapid,
sensitive and in-depth characterization of diverse glycan structures derived from
biological samples. In this study, we described a two-step derivatization
strategy termed linkage-specific sialic acid permethylation (SSAP) consisting of
dimethylamination and permethylation for the improved profiling of glycosylation
by matrix-assisted laser desorption/ionization (MALDI) time-of-fight (TOF) mass
spectrometry (MS). High linkage-specificity (~99%) of SSAP to both the two most
common forms of sialic acid, N-acetylneuraminic acid (Neu5Ac) and N
glycolylneuraminic acid (Neu5Gc), permitted direct discrimination of alpha2,3-
and alpha2,6-linked sialic acids in MALDI-TOF MS. The enhanced intensity (>10
fold) and increased detection limit (>10-fold) of derivatized glycans were valued
for sensitive glycomics. Moreover, the good compatibility and reaction efficiency
of the two steps of SSAP allowed rapid sample preparation (<2 h), benefiting
robust analysis of glycans in a high-throughput manner. The SSAP strategy was
further applied to investigate the protein glycosylation of human serum
associated with rheumatoid arthritis (RA). It was demonstrated that the relative
abundances of individual glycans were different in RA negative and RA positive
samples, and meanwhile the RA patient/control ratios of both alpha2,3- and
alpha2,6-sialylated glycans tended to elevate accompanied with the increase of
sialylation. Those findings of the glycosylation changes occurred in human serum
protein may contribute to the diagnosis of RA. Herein, SSAP derivatization
combined with MALDI-TOF MS exhibits unique advantages for glycomic analysis and
shows potential in glycosylation profiling of therapeutic proteins and clinical
glycan biomarker discovery.
PMID- 28693730
TI - Chiral differentiation of amino acids through binuclear copper bound tetramers by
ion mobility mass spectrometry.
AB - In this study, travelling wave ion mobility mass spectrometry has been used to
investigate chiral differentiation of common chiral amino acids, through
separation of binuclear copper bound tetrameric ions formed with chiral selector
tryptophan, proline, tyrosine, phenylalanine or histidine. Significant chiral
recognition was observed for amino acids with aromatic rings or long and active
side chains, with peak-to-peak resolutions up to 1.826. Tryptophan and histidine
offered better enantioselectivity, compared to other chiral selectors. The
results suggested that the mechanism for chiral recognition in ion mobility mass
spectrometry might be significantly different from that in tandem mass
spectrometry. Linear calibration curves were also established to allow
determination of enantiomeric excess of the analytes by the approach. This study
showed that higher assembly of chiral analyte and chiral selector might enable
better chiral discrimination and ion mobility mass spectrometry could be a
powerful technique for provide qualitative, quantitative and structural
information of chiral analysis.
PMID- 28693731
TI - Simple area determination of strongly overlapping ion mobility peaks.
AB - Coupling of ion mobility with mass spectrometry has brought new frontiers in
separation and quantitation of a wide range of isobaric/isomeric compounds. Ion
mobility spectrometry may separate ions possessing the identical molecular
formula but having different molecular shapes. The separation space in most
commercially available instruments is limited and rarely the mobility resolving
power exceeds one hundred. From this perspective, new approaches allowing for
extracting individual compound signals out of a more complex mixture are needed.
In this work we present a new simple analytical approach based on fitting of
arrival time distribution (ATD) profiles by Gaussian functions and generating of
ATD functions. These ATD functions well describe even distorted ion mobility
peaks of individual compounds and allow for extracting their peaks from
mobilograms of mixtures. Contrary to classical integration, our approach works
well with irregular overlapping peaks. Using mobilograms of standards to generate
ATD functions, poorly separated compounds, e.g. isomers, with identical mass
spectra representing a hard to solve task for various chemometric methods can be
easily distinguished by our procedure. Alternatively ATD functions can be
obtained from ATD profiles of ions unique to individual mixture components (if
such ions exist) and mobilograms of standards are not required. On a set of
hyaluronan-derived oligosaccharides we demonstrated excellent ATD repeatability
enabling the resolution of binary mixtures, including mixtures with minor
component level about 5%. Ion mobility quantitative data of isomers were
confirmed by high performance liquid chromatography.
PMID- 28693732
TI - Wheat germ agglutinin and Lens culinaris agglutinin sensitized anisotropic silver
nanoparticles in detection of bacteria: A simple photometric assay.
AB - Efficacy of anisotropic silver nanoparticles sensitized with wheat germ
agglutinin (WGA) and Lens culinaris agglutinin (LCA) was studied for detection of
Staphylococcus aureus and Escherichia coli. It was demonstrated that interaction
of these nanoparticles with bacteria stabilizes them and prevents their
aggregation upon addition of sodium chloride; such stabilization depends on
bacteria concentration. High concentration of bacteria results in higher
stabilization whereas low concentration leads to aggregation of nanoparticles.
Optical changes as a result of aggregation correlate with bacteria concentration.
The developed approach allows the detection of Gram-positive bacteria (S.aureus)
with the lowest detectable concentration of 103 cells/mL and Gram-negative
bacteria (E. coli) with the lowest detectable concentration of 3 * 103 cells/mL
using WGA-sensitized nanoparticles. In the case of LCA-sensitized nanoparticles
the lowest detection was 5 * 103 cells/mL for S. aureus and 5 * 104 cells/mL for
E. coli.
PMID- 28693733
TI - A fluorescent dyad with large emission shift for discrimination of
cysteine/homocysteine from glutathione and hydrogen sulfide and the application
of bioimaging.
AB - Biothiols, as reactive sulfur species (RSS), play important roles in human
physiology, and they have a close connection of generation and metabolism
pathways among of them. It is challenging to discriminate biothiols from each
other due to the similar chemical structures and properties of them. Herein, we
develop a fluorescent hybrid dyad (CS-NBD) for efficiently discriminating
cysteine (Cys)/homocysteine (Hcy) from glutathione (GSH) and hydrogen sulfide
(H2S) by a dual-channel detection method. CS-NBD performs inherently no
fluorescence in ranging from visible to near infrared region. However, upon
addition of Cys (2-150 MUM)/Hcy (2-200 MUM), CS-NBD generates significant
fluorescence enhancement in two distinct emission bands (Green-Red), while
encounter of GSH (2-100 MUM) or H2S (2-70 MUM) induces the fluorescence increase
only in the red channel. The detection limit was determined to be 0.021 MUM for
Cys, 0.037 MUM for Hcy, 0.028 MUM for GSH, and 0.015 MUM for H2S, respectively
(S/N = 3). The interval distance between two emission bands is up to 163 nm,
which is favourable to acquire the accurate data in measurement due to the
reducing of crosstalk signals. CS-NBD is also successfully applied to distinguish
Cys/Hcy in cellular context by dual-color fluorescence imaging.
PMID- 28693734
TI - Hydrophilic interaction liquid chromatography-mass spectrometry as a new tool for
the characterization of intact semi-synthetic glycoproteins.
AB - Improved methods for detailed characterization of complex glycoproteins are
required in the growing sector of biopharmaceuticals. Hydrophilic interaction
liquid chromatography (HILIC) coupled to high resolution (HR) time-of-flight mass
spectrometric (TOF-MS) detection was examined for the characterization of intact
neo-glycoproteins prepared by chemical conjugation of synthetic saccharides to
the lysine residues of selected recombinant proteins. The separation performances
of three different amide HILIC columns (TSKgel Amide-80, XBridge BEH and
AdvanceBio Glycan Mapping) were tested. Water-acetonitrile gradients and volatile
eluent additives have been explored. Addition of 0.05% (v/v) trifluoroacetic acid
to the mobile phase appeared to be essential for achieving optimum resolution of
intact glycoforms and minimal ion suppression effects. Gradient elution
conditions were optimized for each protein on every column. HILIC stationary
phases were evaluated for the analysis of highly heterogeneous semi-synthetic
derivatives of the same protein (ribonuclease A), and in the enhanced
characterization of TB10.4 and Ag85B glycoconjugates, selected antigens from
Mycobacterium tuberculosis (MTB). HILIC-MS results indicated that the HILIC
selectivity is predominantly governed by size of the conjugated glycans and
number of glycans attached, providing efficient glycoform separation. Moreover,
HILIC separation prior to HRMS detection allowed assignment of several product
impurities. Additional top-down MS/MS experiments confirmed conjugation at the N
terminus of TB10.4 next to its lysine residue. Overall, the obtained results
demonstrate that amide-stationary-phase based HILIC coupled to MS is highly
useful for the characterization of intact neo-glycoproteins allowing assessment
of the number, identity and relative abundance of glycoforms present in the semi
synthetic products.
PMID- 28693735
TI - Because timing is everything, assisting in "Timely" care.
PMID- 28693736
TI - Noisy Networks and Autism.
PMID- 28693737
TI - Charting a Course for Autism Biomarkers.
PMID- 28693738
TI - Genes Orchestrating Brain Function.
PMID- 28693739
TI - Links Between Patterns of Embryonic Spinal Cord Development and Schizophrenia
Risk.
PMID- 28693740
TI - New mechanisms of vascular fibrosis: Role of lysyl oxidase.
PMID- 28693741
TI - Reply.
PMID- 28693742
TI - Impact of Cirrhosis in Patients Who Underwent Surgical Aortic Valve Replacement.
AB - Cirrhosis is known to adversely affect cardiac surgery outcomes. Our objective
was to quantify the morbidity, mortality, and cost that cirrhosis adds to
surgical aortic valve replacement. From 1998 to 2011, 423,789 patients in the
Nationwide Inpatient Sample Healthcare Cost Utilization Project underwent
isolated aortic valve replacement; 2,769 (0.7%) had cirrhosis. Multivariable
linear regression and 1:1 propensity matching were used to determine the effect
of cirrhosis on postsurgical outcomes. The number of patients with cirrhosis who
underwent surgical aortic valve replacement per year more than tripled during the
13-year study period. Patients with cirrhosis were more likely to be younger (p
<0.0001), insured by Medicaid (p <0.0001), and operated on at an academic or high
volume hospital (p <0.05). Risk-adjusted mortality for patients with cirrhosis
was 16%, compared with 5% for patients without cirrhosis. Risk factors for death
included congestive heart failure, fluid and electrolyte imbalances, pulmonary
circulation disorders, and weight loss. Among propensity-matched pairs, patients
with cirrhosis had a higher mortality (odds ratio [OR] 3.6), risk of any
complication [OR 1.5], and acute renal failure (OR 2.2). There was no increased
risk of stroke, wound infection, blood transfusion, or pneumonia. The risk
adjusted length of stay (15 vs 12 days) and cost ($68,000 vs 56,000) were higher
in patients with cirrhosis. In conclusion, the presence of cirrhosis poses a
significant risk of death in patients who underwent surgical aortic valve
replacement. When performed, the cost and length of stay are increased compared
with those without cirrhosis.
PMID- 28693743
TI - Prolongation of the QT Interval and Myocardial Ischemia Are More Pieces of the
"Metabolically Unhealthy Obesity" Puzzle.
PMID- 28693744
TI - Changes in Use of Anticoagulation in Patients With Atrial Fibrillation Within a
Primary Care Network Associated With the Introduction of Direct Oral
Anticoagulants.
AB - Atrial fibrillation (AF) and the decision to anticoagulate is a common problem
faced by primary care physicians. Oral anticoagulation (OAC) is underused,
despite its clear benefits with regard to stroke prevention. We examined OAC
usage between 2010 and 2015, following the introduction of direct oral
anticoagulants (DOACs) and specifically assessed whether more patients were
anticoagulated over time. The study cohort included adult patients aged 18 and
older with AF cared for in an 18-practice primary care network between 2010 and
2015. AF status was assigned each calendar year using a validated electronic
health record algorithm. We examined OAC usage over time in all patients with AF,
and in patients at high risk of stroke (CHA2DS2-VASc >= 2). The proportion of the
population with AF increased over time (2010: 4,920 patients [3.5%], 2015: 6,452
patients [4.0%]). There was no increase in the proportion of patients prescribed
any OAC treatment from 2010 (57.0%) to 2015 (57.4%) (p = 0.41). Similarly, in
patients at high risk of stroke, the proportion anticoagulated did not increase
over time (2010: 61.1%, 2015: 61.7%, p = 0.51). Over the study period, DOAC usage
increased from 0.31% of all patients with AF in 2010 to 18.3% in 2015 (p <
0.001). Patients prescribed DOACs were younger, with lower risk of stroke. In
conclusion, this study showed an increasing proportion of patients with AF over
time in a primary care network. The use of DOACs increased over time; however,
the proportion of patients treated with OAC did not increase over time.
PMID- 28693745
TI - 60-Year-Old Woman With Headache and Fatigue.
PMID- 28693746
TI - So similar yet so different: The two ends of a double strand break.
AB - Homologous recombination (HR) is essential for ensuring proper segregation of
chromosomes in the first round of meiotic division. HR is also crucial for
preserving genomic integrity of somatic cells due to its ability to rescue
collapsed replication forks and eliminate deleterious DNA lesions, such as double
strand breaks (DSBs), interstrand crosslinks, and single-strand DNA gaps. Here,
we review the early steps of HR (homology search and strand exchange), focusing
on the roles of the two ends of a DSB. A detailed overview of the basic HR
machinery and its mechanism for template selection and capture of duplex DNA via
strand exchange is provided. Roles of proteins involved in these steps are
discussed in both mitotic and meiotic HR. Central to this review is the
hypothesis, which suggests that in meiosis, HR begins with a symmetrical DSB, but
the symmetry is quickly lost with the two ends assuming different roles; it
argues that this disparity of the two ends is essential for regulation of HR in
meiosis and successful production of haploid gametes. We also propose a possible
evolutionary reason for the asymmetry of the ends in HR.
PMID- 28693747
TI - Germline BAP1 mutations also predispose to cutaneous squamous cell carcinoma.
PMID- 28693748
TI - Mixed mucinous adenocarcinoma and somatostatinoma of the ampulla of Vater
associated with neurofibromatosis type 1.
PMID- 28693749
TI - Primary gastrointestinal anaplastic large cell lymphoma.
AB - Primary gastrointestinal anaplastic large cell lymphoma (GI-ALCL) is rare. We
report eight new cases. The median age was 61.5 years (range 10-88), most
frequently involving the stomach (n = 3) and small intestine (n = 4). The
neoplastic hallmark cells in all cases expressed CD30. Anaplastic lymphoma kinase
(ALK) protein was expressed in two cases (25%). By in situ hybridisation, all
cases were negative for Epstein-Barr virus and for DUSP22/IRF4 gene
translocation. At a median follow-up time of 37.5 months, four patients died of
disease, one was alive with disease, and three were disease-free. Our literature
review showed that GI-ALCL occurred mainly in older patients and was
characterised by a low rate of ALK expression, a high rate of T-cell lineage, and
a frequent occurrence in the small intestine. Incorporating our two ALK+ GI-ALCL
cases together with the four cases in the literature, the median age was 34 years
(range 10-56), with four (67%) cases in the small intestine. The six patients
were all alive with a median follow-up of 21 months. The 5-year overall survival
of our six patients with ALK- GI-ALCL was 40%, in contrast to 100% with ALK+ GI
ALCL. The prognosis for ALK- GI-ALCL was poor, while that for the ALK+
counterparts was good.
PMID- 28693750
TI - Idelalisib induced CMV gastrointestinal disease: the need for vigilance with
novel therapies.
PMID- 28693751
TI - Cost-effectiveness of 13-valent pneumococcal conjugate vaccine (PCV13) in older
Australians.
AB - BACKGROUND: The 23-valent pneumococcal polysaccharide vaccine (PPV23) has been
funded under the Australia National Immunisation Program (NIP) since January 2005
for those aged >65years and other risk groups. In 2016, PCV13 was accepted by the
Pharmaceutical Benefits Advisory Committee (PBAC) as a replacement for a single
dose of PPV23 in older Australian adults. METHODS: A single-cohort deterministic
multi-compartment (Markov) model was developed describing the transition of the
population between different invasive and non-invasive pneumococcal disease
related health states. We applied a healthcare system perspective with costs
(Australian dollars, A$) and health effects (measured in quality adjusted life
years, QALYs) attached to model states and discounted at 5% annually. We explored
replacement of PPV23 with PCV13 at 65years as well as other age based vaccination
strategies. Parameter uncertainty was explored using deterministic and
probabilistic sensitivity analysis. RESULTS: In a single cohort, we estimated
PCV13 vaccination at the age of 65years to cost ~A$11,120,000 and prevent 39
hospitalisations and 6 deaths from invasive pneumococcal disease and 180
hospitalisations and 10 deaths from community acquired pneumonia. The PCV13
program had an incremental cost-effectiveness ratio of ~A$88,100 per QALY gained
when compared to a no-vaccination, whereas PPV23 was ~A$297,200 per QALY gained.
To fall under a cost-effectiveness threshold of A$60,000 per QALY, PCV13 would
have to be priced below ~A$46 per dose. The cost-effectiveness of PCV13 in
comparison to PPV23 was ~A$35,300 per QALY gained. CONCLUSION: In comparison to
no-vaccination, we found PCV13 use in those aged 65years was unlikely to be cost
effective unless the vaccine price was below A$46 or a longer duration of
protection can be established. However, we found that in comparison to the PPV23,
vaccination with PCV13 was cost-effective. This partly reflects the poor value
for money estimated for PPV23 use in Australia.
PMID- 28693752
TI - Glyphosate and AMPA, "pseudo-persistent" pollutants under real-world agricultural
management practices in the Mesopotamic Pampas agroecosystem, Argentina.
AB - In the Pampas, public concern has strongly risen because of the intensive use of
glyphosate for weed control and fallow associated with biotech crops. The present
study was aimed to evaluate the occurrence and concentration of the herbicide and
its main metabolite (AMPA) in soil and other environmental compartments of the
mentioned agroecosystem, including groundwater, in relation to real-world
agricultural management practices in the region. Occurrence was almost ubiquitous
in solid matrices (83-100%) with maximum concentrations among the higher reported
in the world (soil: 8105 and 38939; sediment: 3294 and 7219; suspended
particulate matter (SPM): 584 and 475 MUg/kg of glyphosate and AMPA). Lower
detection frequency was observed in surface water (27-55%) with maximum
concentrations in whole water of 1.80 and 1.90 MUg/L of glyphosate and AMPA,
indicating that SPM analysis would be more sensitive for detection in the aquatic
ecosystem. No detectable concentrations of glyphosate or AMPA were observed in
groundwater. Glyphosate soil concentrations were better correlated with the total
cumulative dose and total number of applications than the last spraying event
dose, and an increment of 1 mg glyphosate/kg soil every 5 spraying events was
estimated. Findings allow to infer that, under current practices, application
rates are higher than dissipation rates. Hence, glyphosate and AMPA should be
considered "pseudo-persistent" pollutants and a revisions of management
procedures, monitoring programs, and ecological risk for soil and sediments
should be also recommended.
PMID- 28693753
TI - Direct and indirect associations between dysfunctional attitudes, self-stigma,
hopefulness and social inclusion in young people experiencing psychosis.
AB - OBJECTIVE: Social inclusion and vocational activity are central to personal
recovery for young people with psychosis. Studies with people experiencing long
term psychosis suggest negative self-beliefs are important, but less is known
about whether this association is present for young service users or about the
potential influence of positive self-beliefs such as hopefulness. The aim of the
current paper was to investigate the direct and indirect associations between
dysfunctional attitudes, self-stigma, hopefulness, social inclusion and
vocational activity for young people with psychosis. METHOD: A 5-month
longitudinal study was conducted with young psychosis service users. Measures of
dysfunctional attitudes and self-stigma and vocational activity were obtained at
baseline. Measures of hopefulness, social inclusion and vocational activity were
obtained at follow-up. RESULTS: Hopefulness mediates the associations between
self-stigma, social inclusion and vocational activity. Self-stigma may have a
greater influence on social inclusion with age. Dysfunctional attitudes do not
significantly predict social inclusion or change in vocational activity status.
CONCLUSION: Findings suggest that the impact of self-stigma may extend beyond
social and occupational withdrawal and undermine subjective community belonging.
Findings encourage an increased emphasis on facilitating hopefulness for young
people who experience psychosis.
PMID- 28693754
TI - A comprehensive analysis of mitochondrial genes variants and their association
with antipsychotic-induced weight gain.
AB - Antipsychotic Induced Weight Gain (AIWG) is a common and severe side effect of
many antipsychotic medications. Mitochondria play a vital role for whole-body
energy homeostasis and there is increasing evidence that antipsychotics modulate
mitochondrial function. This study aimed to examine the role of variants in
nuclear-encoded mitochondrial genes and the mitochondrial DNA (mtDNA) in
conferring risk for AIWG. We selected 168 European-Caucasian individuals from the
CATIE sample based upon meeting criteria of multiple weight measures while taking
selected antipsychotics (risperidone, quetiapine or olanzapine). We tested the
association of 670 nuclear-encoded mitochondrial genes with weight change (%)
using MAGMA software. Thirty of these genes showed nominally significant P-values
(<0.05). We were able to replicate the association of three genes, CLPB, PARL,
and ACAD10, with weight change (%) in an independent prospectively assessed AIWG
sample. We analyzed mtDNA variants in a subset of 74 of these individuals using
next-generation sequencing. No common or rare mtDNA variants were found to be
significantly associated with weight change (%) in our sample. Additionally,
analysis of mitochondrial haplogroups showed no association with weight change
(%). In conclusion, our findings suggest nuclear-encoded mitochondrial genes play
a role in AIWG. Replication in larger sample is required to validate our initial
report of mtDNA variants in AIWG.
PMID- 28693755
TI - Unraveling interrelationships among psychopathology symptoms, cognitive domains
and insight dimensions in chronic schizophrenia.
AB - INTRODUCTION: Insight in schizophrenia is long known to have a complex
relationship with psychopathology symptoms and cognition. However, very few
studies have examined models that explain these interrelationships. METHODS: In a
large sample derived from the NIMH Clinical Antipsychotic Trials of Intervention
Effectiveness (CATIE) schizophrenia trial (N=1391), we interrogated these
interrelationships for potential causal pathways using structural equation
modeling. Using the NIMH consensus model, latent variables were constructed for
psychopathology symptom dimensions, including positive, negative, disorganized,
excited and depressed from the Positive and Negative Syndrome Scale (PANSS)
items. Neurocognitive variables were created from five predefined domains of
working memory, verbal memory, reasoning, vigilance and processing speed. Illness
insight and treatment insight were tested using latent variables constructed from
the Illness and Treatment Attitude Questionnaire (ITAQ). RESULTS: Disorganized
symptoms had the strongest effect on insight. Illness insight mediated the
relationship of positive, depressed, and disorganized symptoms with treatment
insight. Neurocognition mediated the relationship between disorganized and
treatment insight and depressed symptoms and treatment insight. There was no
effect of negative symptoms on either illness insight or treatment insight. Taken
together, our results indicate overlapping and unique relational paths for
illness and treatment insight dimensions, which could suggest differences in
causal mechanisms and potential interventions to improve insight.
PMID- 28693756
TI - Neglect of the Tropics Is Widespread in Ecology and Evolution: A Comment on
Clarke et al.
PMID- 28693757
TI - Editorial overview: The cell nucleus: New discoveries on nuclear structure,
dynamics and function.
PMID- 28693758
TI - The U.S. Online News Coverage of Mammography Based on a Google News Search.
AB - RATIONALE AND OBJECTIVES: To characterize online news coverage relating to
mammography, including articles' stance toward screening mammography. MATERIALS
AND METHODS: Google News was used to search U.S. news sites over a 9-year period
(2006-2015) based on the search terms "mammography" and "mammogram." The top 100
search results were recorded. Identified articles were manually reviewed.
RESULTS: The top 100 news articles were from the following sources: local news
outlet (50%), national news outlet (24%), nonimaging medical source (13%),
entertainment or culture news outlet (6%), business news outlet (4%), peer
reviewed journal (1%), and radiology news outlet (1%). Most common major themes
were the screening mammography controversy (29%), description of a new breast
imaging technology (23%), dense breasts (11%), and promotion of a public
screening initiative (11%). For the most recent year, article stance toward
screening mammography was 59%, favorable; 16%, unfavorable; and 25%, neutral.
After 2010, there was an abrupt shift in articles' stances from neutral to both
favorable and unfavorable. CONCLUSIONS: A wide range of online news sources
addressed a range of issues related to mammography. National, rather than local,
news sites were more likely to focus on the screening controversy and more likely
to take an unfavorable view. The controversial United States Preventive Services
Task Force guidelines may have influenced articles to take a stance on screening
mammography. As such online news may impact public perception of the topic and
thus potentially impact guideline adherence, radiologists are encouraged to
maintain awareness of this online coverage and to support the online
dissemination of reliable and accurate information.
PMID- 28693759
TI - Management of leakage and stenosis after sleeve gastrectomy.
AB - BACKGROUND: Sleeve gastrectomy is one of the most commonly performed procedures
in obesity and metabolic operation with leakage and stenosis being serious
complications. The management of these complications is challenging, with
different operative options available. The aim of our study was to evaluate the
incidence and management strategies of leakage and stenosis after sleeve
gastrectomy at our institution and to compare our outcomes with those previously
reported in the literature. METHODS: We conducted a retrospective analysis of the
medical records of 49 patients treated for leakage and/or stenosis after
laparoscopic sleeve gastrectomy at our Centre of excellence for bariatric and
metabolic operation, including 25 patients referred to our department from other
hospitals. Outcomes were evaluated using descriptive statistics. RESULTS: Our
study cohort consisted of 49 obese patients, 33 females (66%), with a mean +/-
standard deviation age of 50 +/- 11 years, and body mass index at the time of
laparoscopic sleeve gastrectomy, 51 +/- 8 kg/m2. Postsleeve gastrectomy leakage
was identified in 27 patients (55%), stenosis in 13 (27%), and combined leakage
and stenosis in 9 (18%). Leakage, stenosis, and combined leakage/stenosis were
managed successfully by interventional methods in 85%, 15%, and 22% of cases,
respectively. Conversion into another procedure provided a successful rescue
operation for other patients. We had a 0% mortality rate. CONCLUSION: Most
patients with leakage were managed successfully with interventional methods. The
majority of patients with stenosis or both leakage and stenosis required rescue
operation.
PMID- 28693760
TI - Endothelial Damage During Septic Shock: Significance and Implications for Future
Therapies.
PMID- 28693761
TI - Giants in Chest Medicine: John B. West, MD, PhD, DSc.
PMID- 28693762
TI - Heavenly Whispers.
PMID- 28693763
TI - What I Reply to Well-Meaning People.
PMID- 28693764
TI - Black Hole.
PMID- 28693765
TI - The Spectrum of Changes in the Right Ventricle in ARDS: Dilatation, Dysfunction,
and Acute Cor Pulmonale.
PMID- 28693766
TI - Right Ventricle in ARDS.
PMID- 28693767
TI - Response.
PMID- 28693768
TI - Response.
PMID- 28693769
TI - Inferring Direct Effects of ICU Telemedicine on Cost-Effectiveness.
PMID- 28693770
TI - Response.
PMID- 28693771
TI - Is a Single Initial Procalcitonin Test Sufficient in Septic, Critically Ill
Patients to Minimize Antibiotic Use?
PMID- 28693772
TI - Response.
PMID- 28693773
TI - Is Screening for Pulmonary Embolism in Patients With COPD Necessary?
PMID- 28693774
TI - Response.
PMID- 28693775
TI - The Magic Bullet in Sepsis or the Inflation of Chance Findings?
PMID- 28693776
TI - Response.
PMID- 28693777
TI - Unilateral Do Not Resuscitate Orders: Physician Attitudes and Practices.
PMID- 28693778
TI - Advanced Critical Care Echocardiography: The Intensivist as the ACCE of Hearts.
PMID- 28693779
TI - Should We Get Sniffy About Maximal Inspiratory Pressure?
PMID- 28693780
TI - Research in Obstructive Sleep Disorders in Pediatrics: Past and Possible Future.
PMID- 28693781
TI - A 74-Year-Old Man With Refractory Hypotension After Spine Surgery.
PMID- 28693782
TI - An African American Man in His Late 30s With Lung Cancer Presenting With
Persistent Cough and Hemoptysis.
AB - CASE PRESENTATION: An African American man in his late 30s was referred to the
pulmonary clinic for evaluation of a persistent cough of several weeks' duration.
Cough was productive of mucopurulent sputum mixed with blood. He also noted
generalized weakness and dyspnea with minimal exertion.
PMID- 28693783
TI - A Woman in Her 50s With a Mass in One Lung and a Cavitary Lesion in the Other.
AB - CASE PRESENTATION: A woman in her 50s with no significant medical history
presented with low-grade fever and cough of 3 days' duration, which was
productive of blood-streaked sputum. She was an active smoker, with a 30 pack
year history of smoking. She denied chest pain, chronic cough, exertional
dyspnea, or constitutional symptoms.
PMID- 28693784
TI - A Patient on Airway Pressure Release Ventilation With Sudden Hemodynamic
Collapse.
PMID- 28693785
TI - Introduction to Pediatric Rehabilitation.
PMID- 28693786
TI - Skeletal involvement in type 1 Gaucher disease: Not just bone mineral density.
AB - Gaucher disease is characterized by multi-organ infiltration of phospholipid
laden macrophages. Bone involvement is characterized by typical deformities,
osteopenia/osteoporosis, pathological fractures, and bone marrow infiltration
(avascular osteonecrosis, infarction). Estimation of skeletal disease includes
bone quality that contributes substantially to bone strength. We studied 23 type
1 Gaucher patients (median age 22years, range 3-73) on Enzyme Replacement Therapy
from 2months to 26years (median 7years); 4 patients had pathological fractures,
10 bone infarctions, 6 avascular osteonecrosis. We noninvasively assessed bone
quality by trabecular microarchitecture and macroscopic geometry, using two
innovative dual-energy X-ray absorptiometry tools: Trabecular Bone Score (TBS)
and Hip Structural Analysis (HSA). Bone quality parameters distinguished the
patients with skeletal complications. TBS was significantly lower in patients
with avascular osteonecrosis (p=0.049) and pathological fractures (p=0.024),
while it could not identify those with bone infarctions. Among HSA parameters,
the Cross Sectional Area of the intertrochanteric region and the Buckling Ratio
of the narrow neck allowed the distinction of patients with avascular
osteonecrosis. BMD was low in 11 patients (50%); neither BMD nor HSA were
associated with pathological fractures. The combined evaluation of bone quality
and bone quantity is useful to identify GD patients with more severe skeletal
involvement.
PMID- 28693787
TI - Secretin-Enhanced Magnetic Resonance Cholangiopancreatography for Assessing
Pancreatic Secretory Function in Children.
AB - OBJECTIVE: To assess the accuracy and interrater reproducibility of measurements
of pancreatic secretory function by magnetic resonance cholangiopancreatography
in response to secretin administration and to describe our experience using the
technique to noninvasively assess pancreatic secretory function in a pediatric
population. STUDY DESIGN: In the accuracy study, phantoms with varying fluid
volume (47-206 mL) were imaged using the clinical quantification sequence. Fluid
volume was measured by image segmentation (ImageJ). Measurement accuracy was
expressed in terms of error (absolute and percent) relative to known fluid
volume. In the reproducibility study and clinical experience, 31 patients with
suspected pancreatic disease underwent 33 secretin-enhanced magnetic resonance
cholangiopancreatography exams. Two-dimensional T2-weighted, fat-saturated single
shot fast spin echo sequences were acquired before and after secretin injection
(0.2 ug/kg, max 16 ug). Secreted fluid volume (postsecretin minus presecretin)
was independently measured by 2 blinded reviewers. Between reviewer measurement
reproducibility was assessed based on correlation (Spearman) and bias (Bland
Altman analysis). RESULTS: For the accuracy study, fluid volumes were measured
with mean volume errors of -0.3 to +12.5 mL (percent error -0.03% to +9.0%). For
the reproducibility study, the mean secreted fluid volumes measured by reviewer 1
and reviewer 2 were 79.1 +/- 54.3 mL (range 5.5-215.4) and 77.2 +/- 47.1 mL
(range 6.7-198.1 mL), respectively. Measured secreted fluid volumes were very
strongly correlated (r = 0.922) between reviewers with a bias of only 1.9 mL (95%
limits of agreement -40.5 to 44.2). CONCLUSIONS: Measurement of fluid volume by
magnetic resonance imaging is highly accurate with <10% (<13 mL) error in
measured volume. Measurements of pancreatic secreted fluid volume in response to
secretin by magnetic resonance cholangiopancreatography are highly reproducible
with a bias of <2 mL between reviewers.
PMID- 28693788
TI - Fetal Growth Restriction with Brain Sparing: Neurocognitive and Behavioral
Outcomes at 12 Years of Age.
AB - OBJECTIVE: To study neurocognitive functions and behavior in children with a
history of fetal growth restriction (FGR) with brain sparing. We hypothesized
that children with FGR would have poorer outcomes on these domains. STUDY DESIGN:
Subjects were 12-year-old children with a history of FGR born to mothers with
severe early-onset hypertensive pregnancy disorders (n = 96) compared with a
normal functioning full term comparison group with a birth weight >=2500 g (n =
32). Outcome measures were neurocognitive outcomes (ie, intelligence quotient,
executive function, attention) and behavior. RESULTS: For the FGR group, the mean
ratio of the pulsatility index for the umbilical artery/middle cerebral artery
(UC-ratio = severity of brain sparing) was 1.42 +/- 0.69. The mean gestational
age was 31-6/7 +/- 2-2/7 weeks. The mean birth weight was 1341 +/- 454 g, and
the mean birth weight ratio 0.68 +/- 0.12. Neurocognitive outcomes were
comparable between groups. Parents of children with FGR reported more social
problems (mean T-score 56.6 +/- 7.7; comparison 52.3 +/- 4.3, P < .001, effect
size = 1, 95% CI 0.52-1.46) and attention problems (mean T-score 57.3 +/- 6.9;
comparison 53.6 +/- 4.2, P = .004, effect size = 0.88, 95% CI 0.42-1.33). UC
ratio was not associated with any of the outcomes, but low parental education and
lower birth weight ratio were. CONCLUSIONS: In this prospective follow-up study
of 12-year-old children with a history of FGR and confirmed brain sparing,
neurocognitive functions were comparable with the comparison group, but parent
reported social and attention problem scores were increased.
PMID- 28693789
TI - Real-Life Glycemic Control in Children with Type 2 Diabetes: A Population-Based
Study.
AB - OBJECTIVES: To characterize children and adolescents with type 2 diabetes
mellitus (T2DM) insured by a large health maintenance organization, and to
identify variables associated with treatment quality and disease outcome. STUDY
DESIGN: Children and adolescents diagnosed with T2DM over a 9-year period were
identified from the database of Clalit Health Services, a large health
maintenance organization in Israel (1 213 362 members aged 0-18 years).
Demographic, anthropometric, clinical, and laboratory data were analyzed.
RESULTS: A total of 96 patients (47 males) met our inclusion criteria. The mean
age at diagnosis of T2DM was 14.25 +/- 2.51 years. At the time of diagnosis, the
median hemoglobin A1c (HbA1c) level was 7.8%, and additional components of the
metabolic syndrome were present in 14.9%-67.4% of the patients. At the end of the
follow-up period (3.11 +/- 1.75 years), >50% of the patients were being treated
with insulin; the median HbA1c value was 7.97%, and 44.6% of the patients
achieved the target HbA1c of <7.0%. On multivariate linear regression analysis,
the variables found to predict worse glycemic control (ie, higher HbA1c) were a
higher HbA1c at diagnosis, a higher body mass index SD score at diagnosis, fewer
annual HbA1c tests, and Arabic ethnicity [F(4,81) = 7.139; P < .001; R2 = 0.271].
CONCLUSION: This population-based study of pediatric patients with T2DM
demonstrates that reasonable glycemic control can be achieved in both community
and outpatient hospital settings. Nevertheless, there is room for improvement in
intervention programs to optimize outcomes and decrease the risk of
complications.
PMID- 28693790
TI - Application of metabolomics in sarcoma: From biomarkers to therapeutic targets.
PMID- 28693791
TI - ETV6 and ETV7: Siblings in hematopoiesis and its disruption in disease.
AB - ETV6 (TEL1) and ETV7 (TEL2) are closely-related members of the ETS family of
transcriptional regulators. Both ETV6 and ETV7 have been demonstrated to play key
roles in hematopoiesis, particularly with regard to maintenance of hematopoietic
stem cells and control of lineage-specific differentiation, with evidence of
functional interactions between both proteins. ETV6 has been strongly implicated
in the molecular etiology of a number of hematopoietic diseases, including as a
tumor suppressor, an oncogenic fusion partner, and an important regulator of
thrombopoiesis, but recent evidence has also identified ETV7 as a potential
oncogene in certain malignancies. This review provides an overview of ETV6 and
ETV7 and their contribution to both normal and disrupted hematopoiesis. It also
highlights the key clinical implications of the growing knowledge base regarding
ETV6 abnormalities with respect to prognosis and treatment.
PMID- 28693792
TI - Cholangiocarcinoma.
AB - Biliary tract cancer accounts for <1% of all cancers and affects chiefly an
elderly population, with predominance in men. We distinguish cholangiocarcinoma
(intrahepatic, hilar and distal) and gallbladder cancer, with different
pathogenesis and prognosis. The treatment is based on surgery (whenever
possible), radiotherapy in selected cases, and chemotherapy. The standard
cytotoxic treatment for advanced/metastatic disease is represented by the
combination of gemcitabine and cisplatin, whereas fluoropyrimidines are generally
administered in second line setting. At the present time, no biologic drug
demonstrated a clear efficacy in this cancer, although the molecular
characterisation could provide a promising basis for experimental treatments. A
good supportive care and an early palliative care are warranted in most patients
and should be delivered as a part of a global approach.
PMID- 28693793
TI - Biomarkers of response to PD-1/PD-L1 inhibition.
AB - Immunotherapy is a promising treatment strategy for cancer that has recently
shown unprecedented survival benefits in selected patients. A number of
immunomodulatory agents that target immune system checkpoints such as the
cytotoxic T-lymphocyte antigen 4 (CTLA-4), the programmed death-1 (PD-1) or its
ligand (PD-L1), have received regulatory approval for the treatment of multiple
cancers including malignant melanoma, non-small cell lung cancer, renal cell
carcinoma, classical Hodgkin lymphoma, and recurrent or metastatic head and neck
squamous cell carcinoma. Nevertheless, a substantial proportion of patients
treated with checkpoint inhibitors have little or no benefit while these
treatments are costly and might have associated toxicities. Hence, the
establishment of valid predictors of treatment response has become a priority.
This review summarizes the current evidence around biomarkers of response to PD
1/PD-L1 inhibition, considering features related to the tumor and to the host
immune system.
PMID- 28693794
TI - Adiponectin: Its role in obesity-associated colon and prostate cancers.
AB - Adipose tissue synthesizes many proteins and hormones collectively called
adipokines, which are linked to a number of diseases, including cancer. Low
levels of adiponectin are reported to be a risk factor for obesity-related
cancers including colorectal and prostate cancers. Accordingly, obesity/lifestyle
related diseases, including certain cancers, may be treated by developing drugs
that act specifically on adiponectin levels in circulation. Adiponectin may also
serve as a clinical biomarker in obesity-related diseases. Adiponectin-based
therapies are known to inhibit cancer advancement and thus may provide a
therapeutic approach to delay cancer progression. Better understanding of the
function of adiponectin is of great significance in the fight against cancer.
This timely review is concentrated on the role of adiponectin and the impact of
obesity on the development of cancers, especially colorectal and prostate
cancers.
PMID- 28693795
TI - The role of the systemic inflammatory response in predicting outcomes in patients
with advanced inoperable cancer: Systematic review and meta-analysis.
AB - INTRODUCTION: Cancer remains a leading cause of death worldwide. While a curative
intent is the aim of any surgical treatment many patients either present with or
go onto develop disseminated disease requiring systemic anti-cancer therapy with
a palliative intent. Given their limited life expectancy appropriate allocation
of treatment is vital. It is recognised that systemic chemoradiotherapy may
shorten the quality/quantity of life in patients with advanced cancer. It is
against this background that the present systematic review and meta-analysis of
the prognostic value of markers of the systemic inflammatory response in patients
with advanced cancer was conducted. METHODS: An extensive literature review using
targeted medical subject headings was carried out in the MEDLINE, EMBASE, and
CDSR databases until the end of 2016. Titles were examined for relevance and
studies relating to duplicate datasets, that were not published in English and
that did not have full text availability were excluded. Full texts of relevant
articles were obtained and were then examined to identify any further relevant
articles. RESULTS: The majority of studies were retrospective. The systemic
inflammatory response, as evidenced by a number of markers at clinical
thresholds, was reported to have independent prognostic value, across tumour
types and geographical locations. In particular, C-reactive protein (CRP, 63
studies), albumin (33 studies) the Glasgow Prognostic Score (GPS, 44 studies) and
the Neutrophil Lymphocyte Ratio (NLR, 59 articles) were consistently validated
across tumour types and geographical locations. There was considerable variation
in the thresholds reported to have prognostic value when CRP and albumin were
examined. There was less variation in the thresholds reported for NLR and still
less for the GPS. DISCUSSION: The systemic inflammatory response, especially as
evidenced by the GPS and NLR, has reliable prognostic value in patients with
advanced cancer. Further prospective studies of their clinical utility in
randomised clinical trials and in treatment allocation are warranted.
PMID- 28693796
TI - Regulatory effects of berberine on microRNome in Cancer and other conditions.
AB - Berberine (BBR) is an isoquinoline alkaloid found in different plant families
such as Berberidaceae, Ranunculaceae, and Papaveraceae. BBR is well-known for its
anti-inflammatory, lipid-modifying, anticancer, anti-diabetic, antibacterial,
antiparasitic and fungicide activities. Multiple pharmacological actions of BBR
stem from different molecular targets of this phytochemical. MicroRNAs (miRs) are
single-stranded, evolutionary conserved, small non-coding RNA molecules with a
length of 19-23 nucleotides that are involved in RNA silencing and post
transcriptional regulation of gene expression through binding to the 3'
untranslated region (3'UTR) of target mRNA. MiRs emerged as important regulatory
elements in almost all biological processes like cell proliferation, apoptosis,
differentiation and organogenesis, and numerous human diseases such as cancer and
diabetes. BBR was shown to regulate the expression of miRs in several diseases.
Here, we reviewed the target miRs of BBR and the relevance of their modulation
for the potential treatment of serious human diseases like multiple myeloma,
hepatocellular carcinoma, colorectal cancer, gastric cancer, ovarian cancer and
glioblastoma. The role of miR regulation in the putative anti-diabetic effects of
BBR is discussed, as well.
PMID- 28693797
TI - Azacitidine in adult patients with acute myeloid leukemia.
AB - Azacitidine is recommended front-line treatment for older patients with acute
myeloid leukemia (AML) who are not candidates for intensive treatment regimens,
and was recently granted approval in the European Union for treatment of adult
AML. Reviewed here is azacitidine experience in AML, including: mechanistic and
pharmacokinetic data; safety and efficacy in controlled trials; treatment effects
in AML subpopulations defined by disease characteristics; experience in
unselected patients treated in the community setting; clinical outcomes relative
to other approved AML therapies; and experience with azacitidine-based
combination treatment regimens. Collectively, these data suggest that (a)
azacitidine may prolong overall survival to a similar or greater extent than do
other approved AML treatments, but with less toxicity, (b) azacitidine may be the
preferred treatment option for older patients with unfavorable cytogenetics, and
(c) experience and outcomes with azacitidine in the clinic are similar to those
seen in clinical trials. Continued investigation of combination regimens on an
azacitidine backbone is warranted.
PMID- 28693798
TI - Brain metastases from non-small cell lung carcinoma: Changing concepts for
improving patients' outcome.
AB - The management of Non Small Cell Lung Cancer (NSCLC) brain metastases is
challenging, as this frequent complication negatively impacts patients' quality
of life, and can be a life-threatening event. Through a review of the literature,
we discuss the main therapeutic options and the recent developments that improved
(and complicated) the management of NSCLC brain metastases patients. Most current
validated approaches are local with exclusive or combined surgery, whole brain
radiotherapy (WBRT) and stereotactic radiotherapy (SRT). At the same time, there
is a growing role for systemic treatments that might significantly postpone WBRT.
Targeted therapies efficacy/toxicity profile remains to be defined but predictive
and prognostic molecular factors integration could help to select treatments
fully adapted to life expectancy and progression risk.
PMID- 28693799
TI - The current value of determining the mismatch repair status of colorectal cancer:
A rationale for routine testing.
AB - Colorectal Cancer (CRC) is the third most prevalent cancer in men and women. Up
to 15% of CRCs display microsatellite instability (MSI). MSI is reflective of a
deficient mismatch repair (MMR) system and is most commonly caused by
hypermethylation of the MLH1 promoter. However, it may also be due to autosomal
dominant constitutional mutations in DNA MMR, termed Lynch Syndrome. MSI may be
diagnosed via polymerase chain reaction (PCR) or alternatively,
immunohistochemistry (IHC) can identify MMR deficiency (dMMR). Many institutions
now advocate universal tumor screening of CRC via either PCR for MSI or IHC for
dMMR to guide Lynch Syndrome testing. The association of sporadic MSI with
methylation of the MLH1 promoter and an activating BRAF mutation may offer
further exclusion criteria for genetic testing. Aside from screening for Lynch
syndrome, MMR testing is important because of its prognostic and therapeutic
implications. Several studies have shown MSI CRCs exhibit different
clinicopathological features and prognosis compared to microsatellite-stable
(MSS) CRCs. For example, response to conventional chemotherapy has been reported
to be less in MSI tumours. More recently, MSI tumours have been shown to be
responsive to immune-checkpoint inhibition providing a novel therapeutic
strategy. This provides a rationale for routine testing for MSI or dMMR in CRC.
PMID- 28693800
TI - Review of sequencing platforms and their applications in phaeochromocytoma and
paragangliomas.
AB - Genetic testing is recommended for patients with phaeochromocytoma (PCC) and
paraganglioma (PGL) because of their genetic heterogeneity and heritability. Due
to the large number of susceptibility genes associated with PCC/PGL, next
generation sequencing (NGS) technology is ideally suited for carrying out genetic
screening of these individuals. New generations of DNA sequencing technologies
facilitate the development of comprehensive genetic testing in PCC/PGL at a lower
cost. Whole-exome sequencing and targeted NGS are the preferred methods for
screening of PCC/PGL, both having precise mutation detection methods and low
costs. RNA sequencing and DNA methylation studies using NGS technology in PCC/PGL
can be adopted to act as diagnostic or prognostic biomarkers as well as in
planning targeted epigenetic treatment of patients with PCC/PGL. The designs of
NGS having a high depth of coverage and robust analytical pipelines can lead to
the successful detection of a wide range of genomic defects in PCC/PGL.
Nevertheless, the major challenges of this technology must be addressed before it
has practical applications in the clinical diagnostics to fulfill the goal of
personalized medicine in PCC/PGL. In future, novel approaches of sequencing, such
as third and fourth generation sequencing can alter the workflow, cost, analysis,
and interpretation of genomics associated with PCC/PGL.
PMID- 28693801
TI - Third-line systemic treatment versus best supportive care for advanced/metastatic
gastric cancer: A systematic review and meta-analysis.
AB - This review evaluated the efficacy, toxicities and quality of life of third-line
systemic treatment (TLT) versus best supportive care (BSC) in metastatic gastric
cancer patients after failing two lines of systemic treatment. Six studies were
included, involving 890 participants (TLT: 587, BSC: 303, Asian: 679, 76.3%),
median 53-61 years old, ECOG 0-1 with no major co-morbidities. Compared with BSC,
TLT improved overall survival (HR 0.63; 95% CI 0.46-0.87, corresponding to an
improvement in medial OS from 3.20 to 4.80 months), progression-free survival (HR
0.29; 95% CI 0.18-0.45), objective response rate (RR 5.28; 95% CI 1.00-27.83) and
disease control rate (RR 4.51; 95% CI 2.64-7.71). The efficacy results favoring
TLT should be interpreted with caution for the substantial heterogeneities, wide
confidence intervals and selection bias. More toxicities occurred in the TLT
arms. This review highlighted the paucity of QOL data. Future studies should
focus more on QOL-related outcomes. PROSPERO registration: 2015 CRD42015017873.
PMID- 28693802
TI - The vicious circle of treatment-induced toxicities in locally advanced head and
neck cancer and the impact on treatment intensity.
AB - The intensity of the available treatment approaches for locally-advanced head and
neck cancer (HNC) is at the upper limit of tolerance of acute toxicities. Several
factors including breakthrough cancer pain, mucositis, dysphagia, local and
systemic infections, and nutritional problems are related to treatment intensity.
Particularly, pain, as symptom directly associated with the disease or combined
with other treatment-related factors, has a major impact on quality of life of
HNC patients and ultimately can influence the efficacy of treatments in HNC.
Here, a Multidisciplinary Board of Italian Experts has addressed these issues,
with the aim to identify the unmet need and appropriate strategies for the
maintenance of optimal treatment intensity in HNC.
PMID- 28693803
TI - The see-saw of Keap1-Nrf2 pathway in cancer.
AB - Keap1-Nrf2 pathway is continuously involved in the cytoprotection from oxidative
stress generated due to various factors either extrinsic or intrinsic in origin.
This role of Nrf2 in the response to oxidative stress is well established.
Following oxidative insult, Nrf2 mediates the regulation of the inducible
expression of cytoprotective genes. The level and functional capacity of Nrf2 is
regulated at the post-transcriptional level, mainly through its association with
an actin-associated protein, Keap1. Various studies reported that any discrepancy
from their routine may lead to promotion of tumor as well. So there is need to
explore their role in cytoprotection and tumor promotion if any. This review is
an attempt to critically analyze the available data that may lighten up the
present knowledge and unveil the new regime for cancer prevention and treatment.
PMID- 28693804
TI - Reviewing the current evidence supporting early B-cells as the cellular origin of
Merkel cell carcinoma.
AB - Merkel cell carcinoma (MCC) is a highly malignant skin cancer characterized by
early metastases and poor survival. Although MCC is a rare malignancy, its
incidence is rapidly increasing in the U.S. and Europe. The discovery of the
Merkel cell polyomavirus (MCPyV) has enormously impacted our understanding of its
etiopathogenesis and biology. MCCs are characterized by trilinear
differentiation, comprising the expression of neuroendocrine, epithelial and B
lymphoid lineage markers. To date, it is generally accepted that the initial
assumption of MCC originating from Merkel cells (MCs) is unlikely. This is owed
to their post-mitotic character, absence of MCPyV in MCs and discrepant protein
expression pattern in comparison to MCC. Evidence from mouse models suggests that
epidermal/dermal stem cells might be of cellular origin in MCC. The recently
formulated hypothesis of MCC originating from early B-cells is based on
morphology, the consistent expression of early B-cell lineage markers and the
finding of clonal immunoglobulin chain rearrangement in MCC cells. In this review
we elaborate on the cellular ancestry of MCC, the identification of which could
pave the way for novel and more effective therapeutic regimens.
PMID- 28693805
TI - Editorial: Nitric oxide in plants.
PMID- 28693806
TI - Distribution, sources and contamination assessment of heavy metals in surface
sediments of the South Yellow Sea and northern part of the East China Sea.
AB - Surface sediment samples collected from the South Yellow Sea and northern part of
the East China Sea during spring and autumn, respectively, were analyzed for
grain size, aluminum, and heavy metals (Cr, Ni, Cu, Zn, and Pb) to evaluate heavy
metal levels and the contamination status. The results showed that all of the
heavy metal concentrations met the standard criteria of the Chinese National
Standard Criteria for Marine Sediment Quality. Both the EFs and a multivariate
analysis (PCA) indicated that Cr, Ni, Cu, and Zn were mainly from natural
contributions, while Pb was influenced by anthropogenic inputs, especially during
autumn. The geoaccumulation index of Pb near the mouth of the Yangtze River
suggested that the pollution degree in autumn was heavier than that in spring,
which might be caused by the greater river discharge in summer and more heavy
metal adsorption with finer grain sizes.
PMID- 28693807
TI - Inter-annual variation in the density of anthropogenic debris in the Tasman Sea.
AB - An increasing number of studies highlight the risk of plastic pollution in the
marine environment. However, systematic longitudinal data on the distribution and
abundance of plastic debris remain sparse. Here we present the results of a two
year study of plastic pollution within the Tasman Sea, contrasted with a further
year of data from the same region, in order to document how the density of debris
varies across years in this area. Surface net tows were collected between Hobart,
Tasmania and Sydney, Australia during the spring of 2013 and 2014 and compared
with a subset of data from autumn 2012 from the same region. Substantial inter
annual variation in mean plastic abundance was observed over the three year
period, ranging from to 248.04-3711.64pieceskm-2, confirming the need for
multiple years of sampling to fully estimate the extent of, and trends in,
plastic pollution.
PMID- 28693808
TI - Nuclear reprocessing-related radiocarbon (14C) uptake into UK marine mammals.
AB - To evaluate the transfer of Sellafield-derived radiocarbon (14C) to top predators
in the UK marine environment, 14C activities were examined in stranded marine
mammals. All samples of harbour porpoise (Phocoena phocoena) obtained from the
Irish Sea showed 14C enrichment above background. Mammal samples obtained from
the West of Scotland, including harbour porpoise, grey seals (Halichoerus grypus)
and harbour seals (Phoca vitulina) showed 14C enrichment but to a lesser extent.
This study demonstrates, for the first time, enriched 14C is transferred through
the marine food web to apex predators as a consequence of ongoing nuclear
reprocessing activities at Sellafield. Total Sellafield 14C discharge activity
24months prior to stranding and, in particular, distance of animal stranding site
from Sellafield are significant variables affecting individual 14C activity. 14C
activities of West of Scotland harbour porpoises suggest they did not forage in
the Irish Sea prior to stranding, indicating a high foraging fidelity.
PMID- 28693809
TI - Aliphatic hydrocarbons and triterpane biomarkers in mangrove oyster (Crassostrea
belcheri) from the west coast of Peninsular Malaysia.
AB - The Straits of Malacca is one of the world's busiest shipping routes where
frequent oil spills occur. Rapid development in the west coast of Peninsular
Malaysia is the other major source of petroleum pollution in this narrow
waterway. In order to identify occurrence and origin of hydrocarbons in the
Straits, mangrove oysters (Crassostrea belcheri) were collected from five
sampling locations and analysed for n-alkanes and biomarkers. Soxhlet apparatus
and two step column chromatography were used for extraction, purification and
fractionation of the oysters. Petroleum origin n-alkanes were detected in
majority of the sampling locations which is indicative of anthropogenic
activities in this region. Using source and maturity diagnostic ratios for
hopanes revealed used crankcase oil as the main source of petroleum hydrocarbons
in oysters from all sampling locations except for the Pulau Merambong where
signature of South East Asia crude oil (SEACO) was detected.
PMID- 28693810
TI - Chemical monitoring of Swedish coastal waters indicates common exceedances of
environmental thresholds, both for individual substances as well as their
mixtures.
AB - Chemical pollution was monitored and assessed along the Swedish west coast. 62 of
172 analyzed organic chemicals were detected in the water phase of at least one
of five monitored sites. A Concentration Addition based screening-level risk
assessment indicates that all sites are put at risk from chemical contamination,
with total risk quotients between 2 and 9. Only at one site did none of the
individual chemicals exceeded its corresponding environmental threshold (PNEC,
EQS). The monitoring data thus demonstrate a widespread blanket of diffuse
pollution, with no clear trends among sites. Further issues critical for the
environmental chemical risk assessment include the challenges to achieve
sufficiently low levels of detection, especially for hormones and cypermethrin (a
pyrethroid insecticide), the appropriate consideration of non-detects and the
limited availability of reliable PNECs and EQS values.
PMID- 28693811
TI - Marine debris ingestion by the South American Fur Seal from the Southwest
Atlantic Ocean.
AB - In this paper, we examined the ingestion of marine debris (MD) in South American
fur seals (SAFS), Arctocephalus australis, found dead in coastal beaches of
northern Argentina and southern Brazil. Seven percent of 133 SAFS analyzed
presented marine debris in their stomach (n=10), with no differences between
sampling countries (Brazil n=7, Argentina n=3) and sexes (female=3; male=6).
However, significant differences were observed between ages classes, with MD
exclusively present in stomach contents of young specimens. Plastics represents
90% of MD ingested by the SAFS, whereas regarding the source, fishery-related
items (e.g. monofilament lines) were the main MD (70%), with a lesser proportion
of packaging (e.g. pieces of bags). Low numbers but large size pieces of MD were
found in each stomach affected. Negative effects on the individuals could not be
fully evaluated. Therefore, the potential impacts of the marine debris to the
SAFS deserve further elucidation.
PMID- 28693812
TI - Predictions, precision, and agentive attention.
AB - Ransom, Fazelpour, and Mole (this journal - 2017) raise an important puzzle for
the 'prediction error minimization' account of cognitive processing. That account
depicts all cognitive processing as fundamentally in the business of minimizing
prediction errors concerning the evolving flow of sensory information. One of the
cornerstones of these highly ambitious, would-be unifying accounts is their
depiction of attention as nothing other than the process of optimizing the
precision (inverse variance) of critical prediction error signals. But that
story, Ransom et al. suggest, cannot accommodate voluntary shifts of attention.
In this paper, I show why this challenge to the grand unifying project fails. It
fails because it locates the origins of voluntary attention in complexes of
unanalyzed desire rather than in changing complexes of beliefs.
PMID- 28693813
TI - Intensity and memory characteristics of near-death experiences.
AB - Memories of Near-Death Experiences (NDEs) seem to be very detailed and stable
over time. At present, there is still no satisfactory explanation for the NDEs'
rich phenomenology. Here we compared phenomenological characteristics of NDE
memories with the reported experience's intensity. We included 152 individuals
with a self-reported "classical" NDE (i.e. occurring in life-threatening
conditions). All participants completed a mailed questionnaire that included a
measure of phenomenological characteristics of memories (the Memory
Characteristics Questionnaire; MCQ) and a measure of NDE's intensity (the Greyson
NDE scale). Greyson NDE scale total score was positively correlated with MCQ
total score, suggesting that participants who described more intense NDEs also
reported more phenomenological memory characteristics of NDE. Using MCQ items,
our study also showed that NDE's intensity is associated in particular with
sensory details, personal importance and reactivation frequency variables.
PMID- 28693814
TI - Open letter to the UN's new health chief from "Alternative Nobel Prize"
laureates.
PMID- 28693815
TI - Comorbid mild traumatic brain injury increases pain symptoms in patients
suffering from an isolated limb fracture.
AB - OBJECTIVES: This study seeks to evaluate the effects of a mild traumatic brain
injury (mTBI) on pain in patients with an isolated limb fracture (ILF) when
compared to a matched cohort group with no mTBI (control group). PATIENTS AND
METHODS: All subjects included in this observational study suffered from an ILF.
Groups were matched according to the type of injury, sex, age, and time since the
accident. Main outcome measurements were: Standardized semi-structured interviews
at follow-up of a Level I Trauma Center, and a questionnaire on fracture-related
pain symptoms. Factors susceptible to influence the perception of pain, such as
age, sex, severity of post-concussive symptoms, and worker compensation were also
assessed. RESULTS: A total of 68 subjects (36 females; 45 years old) with an ILF
were selected, 34 with a comorbid mTBI and 34 without (24/34 with an upper limb
fracture per group, 71% of total sample). Patients with mTBI and an ILF reported
significantly higher pain scores at the time of assessment (mean: 49days, SD:
34.9), compared to the control group (p<0.0001; mean difference 2.8, 95%
confidence interval 1.8-4.0). Correlational analyses show no significant
association between the level of pain and factors such as age, sex, severity of
post-concussive symptoms, and worker compensation. CONCLUSIONS: Results suggest
that mTBI exacerbate perception of pain in the acute phase when occurring with an
ILF, and were not explained by age, sex, post-concussive symptoms, or worker
compensation. Rather, it appears possible that neurological sequelae induced by
mTBI may interfere with the normal recovery of pain following trauma.
PMID- 28693816
TI - Anterior pedicle spreader reduction for unilateral cervical facet dislocation.
AB - OBJECTIVE: The anterior only surgical procedure including discectomy, open
reduction and fusion is used as a recommended approach in the treatment of
unilateral cervical facet dislocations, but is difficult to achieve satisfactory
anterior open reduction by vertebra distractor to spread the facet joints,
especially for delayed management of unilateral cervical facet dislocation (7
21days). The goal of this study was to report an anterior pedicle spreader
technique to distract directly the facet joint for anterior reduction and the
results of 4 patients with successful application and describe safety. METHODS:
Four patients with unilateral cervical facet dislocation who failed to open
anterior reduction by vertebra spreader procedure were surgically treated by the
anterior pedicle spreader reduction. In these 4 patients (3 males and 1 female),
the distribution of spine level was from C4/5 to C6/7; the neurological status
was comprised 2 patients with ASIA E, 1 with D and 1 with A; the surgical
management was ranged from 7 to 18days. After discectomy, if failed to open
anterior reduction procedure, the anterior pedicle spreader was inserted along
the pedicle axis with the fluoroscope-assisted view imaging. The spreader was
distracted directly to the facet joint and pushed in a caudad direction to
achieve posterior translation of the upper segment. RESULTS: Postoperatively, all
patients had obtained successful reduction and satisfactory anatomic sagittal
alignment. There was no complication owing to the use of this technique. The ASIA
A showed no neurological improvement; the patient with ASIA D was improved
neurologically to ASIA E; no ASIA E patients showed neurological deterioration.
CONCLUSIONS: Anterior pedicle spreader reduction represents an efficacious but
technically challenging option for the delayed treatment of unilateral cervical
facet dislocation.
PMID- 28693817
TI - Investigation of perioperative hidden blood loss of unstable intertrochanteric
fracture in the elderly treated with different intramedullary fixations.
AB - OBJECTIVE: Our aim was to investigate perioperative hidden blood loss (PHBL) of
unstable intertrochanteric fracture (UIF) in the elderly treated with different
intramedullary fixations. PATIENTS AND METHODS: 120 consecutive elderly patients
with UIF treated by intramedullary nails between January 2013 and September 2016
were enrolled in the retrospective study, including 52 patients (mean age 79.6+/
6.3) for the Third generation Gamma Nail (TGN), 51 patients (mean age 79.3+/-7.4)
for the Proximal Femoral Nail Anti-rotation (PFNA), 17 patients (mean age 76.2+/
5.8) for the Intertrochanteric Antegrade Nail (InterTan). The PHBL and total
blood loss (TBL) were calculated based on the haematocrit change from admission
to 72h after the operation. The differences of perioperative visible blood loss
(PVBL), PHBL, and TBL among TGN, PFNA, and InterTan were compared. The
statistical analysis was made using One-way ANOVA for comparison among groups,
and Mann-Whitney U test was conducted to a direct comparison between two
procedures. RESULTS: The mean TBL of all patients was 911.3mL (range, 446.8
1697.3mL), whereas the mean PHBL was 771.8mL (range, 331.5-1756.5mL), being about
84.5% of TBL. The PVBL in the TGN group was 201.4+/-101mL, the TBL was 871.3+/
196.1mL, the PHBL was 709.4+/-181mL. In the PFNA group, the PVBL was 147.3+/
81.6mL, the TBL was 892.6+/-234.8mL, and the PHBL was 787.7+/-250.9mL. The
InterTan group had a PVBL of 246.5+/-89.7mL, the TBL was 1086.1+/-198.1mL where
the PHBL was 910+/-167.9mL. The patients in the InterTan group had the largest
amount of PHBL and TBL among three groups (P<0.01), there was no difference
between TGN and PFNA group (P=0.2141). CONCLUSIONS: Elderly patients with UIF
treated by intramedullary fixations always have a significant amount of PHBL,
which is much greater than that observed intra-operatively. Regular perioperative
measurements of full blood count are necessary to avoid anaemia. InterTan nail is
associated with a significantly higher PHBL than that of TGN and PFNA, which
needs to be monitored carefully in usual clinical practice.
PMID- 28693818
TI - Arterial wall remodeling under sustained axial twisting in rats.
AB - Blood vessels often experience torsion along their axes and it is essential to
understand their biological responses and wall remodeling under torsion. To this
end, a rat model was developed to investigate the arterial wall remodeling under
sustained axial twisting in vivo. Rat carotid arteries were twisted at 180
degrees along the longitudinal axis through a surgical procedure and maintained
for different durations up to 4weeks. The wall remodeling in these twisted
arteries was examined using histology, immunohistochemistry and fluorescent
microscopy. Our data showed that arteries remodeled under twisting in a time
dependent manner during the 4weeks post-surgery. Cell proliferation, MMP-2 and
MMP-9 expressions, medial wall thickness and lumen diameter increased while
collagen to elastin ratio decreased. The size and number of internal elastic
lamina fenestrae increased with elongated shapes, while the endothelial cells
elongated and aligned towards the blood flow direction gradually. These results
demonstrated that sustained axial twisting results in artery remodeling in vivo.
The rat carotid artery twisting model is an effective in vivo model for studying
arterial wall remodeling under long-term torsion. These results enrich our
understanding of vascular biology and arterial wall remodeling under mechanical
stresses.
PMID- 28693819
TI - Haemodynamics and stresses in abdominal aortic aneurysms: A fluid-structure
interaction study into the effect of proximal neck and iliac bifurcation angle.
AB - Our knowledge of how geometry influences abdominal aortic aneurysm (AAA)
biomechanics is still developing. Both iliac bifurcation angle and proximal neck
angle could impact the haemodynamics and stresses within AAA. Recent comparisons
of the morphology of ruptured and intact AAA show that cases with large iliac
bifurcation angles are less likely to rupture than those with smaller angles. We
aimed to perform fluid-structure interaction (FSI) simulations on a range of
idealised AAA geometries to conclusively determine the influence of proximal neck
and iliac bifurcation angle on AAA wall stress and haemodynamics. Peak wall shear
stress (WSS) and time-averaged WSS (TAWSS) in the AAA sac region only increased
when the proximal neck angle exceeded 30 degrees . Both peak WSS (p<0.0001) and
peak von Mises wall stress (p=0.027) increased with iliac bifurcation angle,
whereas endothelial cell activation potential (ECAP) decreased with iliac
bifurcation angle (p<0.001) and increased with increasing neck angle. These
observations may be important as AAAs have been shown to expand, develop thrombus
and rupture in areas of low WSS. Here we show that AAAs with larger iliac
bifurcation angles have higher WSS, potentially reducing the likelihood of
rupture. Furthermore, ECAP was lower in AAA geometries with larger iliac
bifurcation angles, implying less likelihood of thrombus development and wall
degeneration. Therefore our findings could help explain the clinical observation
of lower rupture rates associated with AAAs with large iliac bifurcation angles.
PMID- 28693820
TI - Central glucagon like peptide-1 inhibits reflex swallowing elicited by the
superior laryngeal nerve via caudal brainstem in the rat.
AB - The effects of glucagon like peptide-1 (GLP-1) on reflex swallowing were examined
using anaesthetized rats. GLP-1 was injected into the dorsal vagal complex (DVC)
using glass micropipettes. Swallowing was induced by repeated electrical
stimulation of the central cut end of the superior laryngeal nerve (SLN) and was
identified by the electromyogram lead penetrated in the mylohyoide muscle through
bipolar electrodes. Microinjection of GLP-1 into the medial DVC (M-DVC) increased
the frequency of swallowing during the electrical stimulation of the SLN and
extended the latency of the first swallowing. Microinjection of GLP-1 into the
lateral DVC (L-DVC) did not change the frequency of swallowing or the latency of
the first swallowing. Neither the injection of vehicle into the M-DVC nor L-DVC
affected swallowing frequency. Pre-injection of exendin (5-39), a GLP-1 receptor
antagonist, attenuated the degree of suppression of swallowing frequency induced
by the administration of GLP-1 in addition to shortening the latency of the first
swallowing. To identify the effective site of GLP-1, lesion experiments were
performed. Electrical lesion of the commissural part of the NTS (cNTS) and the
vacuum removal of the area postrema (AP) did not affect the inhibition of reflex
swallowing induced by the injection of GLP-1 into the M-DVC. Electrical lesion of
the medial nucleus of the NTS (mNTS) and its vicinity abolished the inhibitory
effects of swallowing induced by the injection of GLP-1. These results suggest
that GLP-1 inhibits reflex swallowing via the mNTS in the dorsal medulla.
PMID- 28693821
TI - Synchronizing MIDI and wireless EEG measurements during natural piano
performance.
AB - Although music performance has been widely studied in the behavioural sciences,
less work has addressed the underlying neural mechanisms, perhaps due to
technical difficulties in acquiring high-quality neural data during tasks
requiring natural motion. The advent of wireless electroencephalography (EEG)
presents a solution to this problem by allowing for neural measurement with
minimal motion artefacts. In the current study, we provide the first validation
of a mobile wireless EEG system for capturing the neural dynamics associated with
piano performance. First, we propose a novel method for synchronously recording
music performance and wireless mobile EEG. Second, we provide results of several
timing tests that characterize the timing accuracy of our system. Finally, we
report EEG time domain and frequency domain results from N=40 pianists
demonstrating that wireless EEG data capture the unique temporal signatures of
musicians' performances with fine-grained precision and accuracy. Taken together,
we demonstrate that mobile wireless EEG can be used to measure the neural
dynamics of piano performance with minimal motion constraints. This opens many
new possibilities for investigating the brain mechanisms underlying music
performance.
PMID- 28693822
TI - Corrigendum to "Cisplatin and photodynamic therapy exert synergistic inhibitory
effects on small-cell lung cancer cell viability and xenograft tumor growth"
[Biochem. Biophys. Res. Comm. 489/3 (2017) 567-572].
PMID- 28693823
TI - Feasibility of Hippocampal Avoidance Radiotherapy for Glioblastoma.
AB - With improvements in survival for good performance status patients and in
specific molecular subtypes of glioblastoma, some patients will survive to
develop significant neurocognitive dysfunction. This retrospective planning study
quantified hippocampal radiation doses in patients with glioblastoma receiving
radical chemo-radiotherapy and compared this with the radiation doses that showed
clinical correlation with neurocognitive dysfunction, and evaluated the potential
for clinically meaningful hippocampal dose reduction using helical
TomoTherapy(r).
PMID- 28693824
TI - Dispersive solid-phase microextraction with graphene oxide based molecularly
imprinted polymers for determining bis(2-ethylhexyl) phthalate in environmental
water.
AB - A novel graphene oxide-molecularly imprinted polymers (GO-MIPs) was prepared and
applied for selective extraction and preconcentration of bis(2-ethylhexyl)
phthalate (DEHP) in environmental water samples by using the dispersive solid
phase microextraction (DSPME) method. The GO-MIPs was synthesized via
precipitation polymerization using GO, DEHP, methacrylic acid, and ethylene
dimethacrylate as supporting materials, template molecules, functional monomer,
and cross-linker, respectively. The prepared GO-MIPs were characterized by
scanning electron microscope and Fourier transform infrared spectroscopy. The GO
MIPs-DSPME conditions including type and volume of elution solvents, adsorbents
amount, initial concentration of DEHP, pH and ionic strength of water samples
were investigated. Under optimized conditions, the DEHP was selectively and
effectively extracted in real water samples and enrichment factors of over 100
fold were achieved. Good linearity was obtained with correlation coefficients
(R2) over 0.999 and the detection limit (S/N=3) was 0.92ngmL-1. The average
recoveries of the spiked samples at three concentration levels of DEHP ranged
from 82% to 92% with the relative standard deviations less than 6.7%. The results
indicated that the proposed GO-MIPs-DSPME extraction protocol combined with HPLC
UV determination could be applied for selective and sensitive analysis of trace
DEHP phthalate in environmental water samples.
PMID- 28693825
TI - Sample-independent approach to normalize two-dimensional data for orthogonality
evaluation using whole separation space scaling.
AB - Orthogonality is a key parameter that is used to evaluate the separation power of
chromatography-based two-dimensional systems. It is necessary to scale the
separation data before the assessment of the orthogonality. Current scaling
approaches are sample-dependent, and the extent of the retention space that is
converted into a normalized retention space is set according to the retention
times of the first and last analytes contained in a unique sample to elute. The
presence or absence of a highly retained analyte in a sample can thus
significantly influence the amount of information (in terms of the total amount
of separation space) contained in the normalized retention space considered for
the calculation of the orthogonality. We propose a Whole Separation Space Scaling
(WOSEL) approach that accounts for the whole separation space delineated by the
analytical method, and not the sample. This approach enables an orthogonality
based evaluation of the efficiency of the analytical system that is independent
of the sample selected. The WOSEL method was compared to two currently used
orthogonality approaches through the evaluation of in silico-generated
chromatograms and real separations of human biofluids and petroleum samples.
WOSEL exhibits sample-to-sample stability values of 3.8% on real samples,
compared to 7.0% and 10.1% for the two other methods, respectively. Using real
analyses, we also demonstrate that some previously developed approaches can
provide misleading conclusions on the overall orthogonality of a two-dimensional
chromatographic system.
PMID- 28693827
TI - Giovanni Boccaccio's (1313-1375) disease and demise: The final untold tale of
liver and heart failure.
AB - Giovanni Boccaccio's fatal disease(s) and cause of death have long remained a
mystery. Now, for the first time, a thorough multidisciplinary reassessment has
finally been carried out. By combining philological and clinical approaches, it
is at last possible to suggest a solid retrospective diagnosis based upon a study
of his correspondence, poetry and iconography, as well as references to his
physical decay in coeval and later sources. It would appear that he suffered over
the last three years of his life from hepatic and cardiac failure, conditions
that resulted in edema and potentially even hepatic carcinoma. Focusing on an
unusually well-documented case from the Middle Ages, this analysis of
exceptionally high informative value reconstructs the symptoms of his medical
conditions and finally permits us to clarify and explain the historical feaures,
presentations and evolutionary history of the case at hand.
PMID- 28693826
TI - Genome-wide Mapping of the Nucleosome Landscape by Micrococcal Nuclease and
Chemical Mapping.
AB - Nucleosomes regulate the transcription output of the genome by occluding the
underlying DNA sequences from DNA-binding proteins that must act on it. Knowledge
of the precise locations of nucleosomes in the genome is thus essential towards
understanding how transcription is regulated. Current nucleosome-mapping
strategies involve digesting chromatin with nucleases or chemical cleavage
followed by high-throughput sequencing. In this review, we compare the
traditional micrococcal nuclease (MNase)-based approach with a chemical cleavage
strategy, with discussion on the important insights each has uncovered about the
role of nucleosomes in shaping transcriptional processes.
PMID- 28693828
TI - Inhibition of plaque progression and promotion of plaque stability by glucagon
like peptide-1 receptor agonist: Serial in vivo findings from iMap-IVUS in
Watanabe heritable hyperlipidemic rabbits.
AB - BACKGROUND AND AIMS: Glucagon-like peptide-1 (GLP-1) is thought to inhibit
development of aortic atherosclerosis and plaque formation. However, whether GLP
1 stabilizes fully developed atherosclerotic plaque or alters the complicated
plaque composition remains unclarified. METHODS: Ten Watanabe heritable
hyperlipidemic (WHHL) rabbits were divided into GLP-1 receptor agonist treatment
group and control group. After confirmation of atherosclerotic plaques in
brachiocephalic arteries by iMap intravascular ultrasound (iMAP-IVUS), GLP-1
receptor agonist lixisenatide was administered to WHHL rabbits at 30 nmoL/kg/day
for 12 weeks by osmotic pump. An equal volume of normal saline was administered
in a control group. After evaluation by iMAP-IVUS at 12 weeks, brachiocephalic
arteries were harvested for pathological histological analysis. RESULTS: iMAP
IVUS analysis revealed larger fibrotic plaque components and smaller necrotic and
calcified plaque components in the GLP-1 group than in the control group;
%fibrotic area: 66.30 +/- 2.06% vs. 75.14 +/- 2.62%, p < 0.01, %necrotic area:
23.25 +/- 1.87% vs. 16.17 +/- 2.27%, p = 0.02, %calcified area: 2.15 +/- 0.24%
vs. 1.00 +/- 0.18%, p < 0.01), indicating that GLP-1 receptor agonist might
modify plaque composition and increase plaque stability. Histological analysis
confirmed that GLP-1 receptor agonist treatment improved smooth muscle cell (SMC)
rich plaque with increased fibrotic content. Furthermore, plaque macrophage
infiltration and calcification were significantly reduced by GLP-1 receptor
agonist treatment; %SMC area: 6.93 +/- 0.31% vs. 8.14 +/- 0.48%, p = 0.02;
%macrophage area: 9.11 +/- 0.80% vs. 6.19 +/- 0.85%, p < 0.01; %fibrotic area:
54.75 +/- 1.63% vs. 69.60 +/- 2.12%, p = 0.02; %calcified area: 3.25 +/- 0.67%
vs. 0.75 +/- 0.15%, p = 0.02). CONCLUSIONS: GLP-1 receptor agonist inhibited
plaque progression and promoted plaque stabilization by inhibiting plaque growth
and modifying plaque composition.
PMID- 28693829
TI - Antiretroviral therapies and cardiovascular risk: True or false?
PMID- 28693830
TI - Reply to "Bioinformatics analysis in type 1 diabetes increases retention of low
density lipoprotein in the atherosclerosis-prone area of the murine aorta".
PMID- 28693831
TI - Response to the letter to the editor regarding an article "Bilateral striatal
necrosis caused by a founder mitochondrial 14459G>A mutation in two independent
Japanese families".
PMID- 28693832
TI - Scaled consensus seeking in multiple non-identical linear autonomous agents.
AB - Scaled consensus problem is studied for a heterogeneous multi-agent system
composed of non-identical stable linear agents, and a leader-following scaled
consensus algorithm is designed. By using frequency-domain analysis, consensus
conditions are obtained for the agents without communication delay under
undirected and directed topologies, respectively. Moreover, consensus criteria
are also gained for the agents suffering from communication delay under directed
topology. Simulation examples show the correctness of theoretical results.
PMID- 28693833
TI - Relay tracking control for second-order multi-agent systems with damaged agents.
AB - This paper investigates a situation where smart agents capable of sensory and
mobility are deployed to monitor a designated area. A preset number of agents
start tracking when a target intrudes this area. Some of the tracking agents are
possible to be out of order over the tracking course. Thus, we propose a
cooperative relay tracking strategy to ensure the successful tracking with
existence of damaged agents. Relay means that, when a tracking agent quits
tracking due to malfunction, one of the near deployed agents replaces it to
continue the tracking task. This results in jump of tracking errors and dynamic
switching of topology of the multi-agent system. Switched system technique is
employed to solve this specific problem. Finally, the effectiveness of proposed
tracking strategy and validity of the theoretical results are verified by
conducting a numerical simulation.
PMID- 28693834
TI - Distributed adaptive asymptotically consensus tracking control of uncertain Euler
Lagrange systems under directed graph condition.
AB - In this paper, a backstepping based distributed adaptive control scheme is
proposed for multiple uncertain Euler-Lagrange systems under directed graph
condition. The common desired trajectory is allowed totally unknown by part of
the subsystems and the linearly parameterized trajectory model assumed in
currently available results is no longer needed. To compensate the effects due to
unknown trajectory information, a smooth function of consensus errors and certain
positive integrable functions are introduced in designing virtual control inputs.
Besides, to overcome the difficulty of completely counteracting the coupling
terms of distributed consensus errors and parameter estimation errors in the
presence of asymmetric Laplacian matrix, extra information transmission of local
parameter estimates are introduced among linked subsystem and adaptive gain
technique is adopted to generate distributed torque inputs. It is shown that with
the proposed distributed adaptive control scheme, global uniform boundedness of
all the closed-loop signals and asymptotically output consensus tracking can be
achieved.
PMID- 28693835
TI - [Sudden cardiac death: A better understanting for a better prevention].
AB - Sudden cardiac death is defined as a natural and unexpected death, in a previous
apparently healthy individual. It represents a major public health issue, with up
to 50% of the cardiovascular mortality. Using data from the Paris Sudden Death
Expertise Centre registry, this article summarises the main cardiovascular
abnormalities associated with sudden cardiac death, the different preventives
approaches, and provides a systematic diagnostic approach.
PMID- 28693836
TI - [Non-inferiority and equivalence trials: Key methodological issues].
AB - Non-inferiority and equivalence trials aim to promote new treatments that are not
expected to be superior to existing ones in a given indication. In order to
compensate for a possible loss of efficacy, the new treatment should offer other
advantages compared to the reference treatment, a better safety of use for
example. Their methods somewhat differ from those of superiority trials, often
better known to the medical community. This article presents the key points of
the methodology of non-inferiority and equivalence trials in order to inform the
readers of such trials about the issues and critical points. The general
methodology (hypotheses, decision rules, number of subjects required, and
strategy of analysis) is presented using examples and graphic illustrations. The
issues and critical points are identified and discussed, in particular the choice
of the comparator and of the margin of non-inferiority.
PMID- 28693837
TI - [Should doses of antibiotics be adjusted?]
AB - While we are confronted with the major increase in antibiotic resistance, the
preservation of existing antibiotics has become an absolute necessity both to
achieve therapeutic success and to limit the risks of the emergence of
resistance. The optimization of antibiotic use and dosages must have a threefold
objective: guarantee antibacterial efficacy, limit toxicities and limit emergence
of resistant strains. However, with the increase in the number of
multipathological patients, particularly those with renal or hepatic impairment,
the increase in the number of patients with extreme weights and the use of
antibiotics with narrower therapeutic margins, the adaptation of antibiotic
dosages is becoming increasingly important. By reminding some principles of
pharmacokinetics and pharmacodynamics of antibiotics (PK/PD), the necessary
objectives for clinical effectiveness of most antibiotic classes are reviewed and
several examples of situations where dosage adjustments are necessary will be
given. In particular, adjustment of antibiotic dosages in obese patients will be
discussed. Adaptation is not limited to the adaptation of the total daily dose.
The PK/PD parameters also tell us that the mode of administration (intermittent
versus continuous, number of injections per day, etc.) is also an essential point
to consider. By taking examples concerning some molecules, infections and
difficult clinical situations, we review situations in which dosage adjustments
appear necessary.
PMID- 28693838
TI - Socioeconomic status, gender, and burn injury: A retrospective review.
AB - Burn injury rates appear to be influenced by socioeconomic status (SES) and
gender globally, but the impact of poverty and gender on burn injury has not been
studied in a developed country. This study was a retrospective chart review
conducted at a regional burn center in the Southwest US that included 340
patients with TBSA burns >15%. SES was determined using zip code and US census
data. The distribution of mechanism of injury was significantly different by
gender (chi2(6) = 36.14, p < 0001), but not significantly different by SES
(chi2(12) = 19.68, p = 0.073). Burn rates in women was found to have a
significant and linear increase (chi2 = 13.8513, p = 0.001) with increasing
poverty. Women had higher frequencies of being burned at home, and men had higher
frequencies of being burned at work. While poverty did not appear to increase the
risk of burn injury overall in a mixed population, it was associated with a
significant increase in the risk of burn injury in women. Thus, strategies for
decreasing risk factors should be targeted toward low SES females and the working
male.
PMID- 28693839
TI - Outcome of incisional hernia repair in patients with Inflammatory Bowel Disease.
AB - BACKGROUND: Incisional Hernia (IH) repair in patients with Inflammatory Bowel
Disease (IBD) has not been well studied. METHODS: Outcomes of 170 patients with
IBD who underwent IH repair were included in the study. RESULTS: The incidence of
recurrence after IH repair in IBD is 27%. Patients with Crohn's disease (CD) had
larger defects at the time of repair, higher proportion of bowel resection and a
longer postoperative stay when compared to Ulcerative colitis (UC). The only
significant predictor of recurrence after IH repair was the number of previous
bowel resections prior to hernia repair (HR 1.59, p < 0.01). Three cases (10%) of
late onset enterocutaneous fistulas were identified in patients who underwent IH
repair with synthetic mesh inlay. CONCLUSION: Surgical repair results in a
recurrence of IH in 27% of patients with IBD. The number of previous bowel
resections is the only factor that correlates with development of recurrent IH in
IBD.
PMID- 28693840
TI - Long-term outcomes of laparoscopic adjustable gastric banding.
AB - BACKGROUND: Laparoscopic adjustable gastric banding (LAGB) is an option for the
treatment of severe obesity. Few US studies have reported long-term outcomes. We
aimed to present long-term outcomes with LAGB. METHODS: Retrospective study of
patients who underwent LAGB at an academic medical center in the US from 1/2005
to 2/2012. Outcomes included weight loss, complications, re-operations, and LAGB
failure. RESULTS: 208 patients underwent LAGB. Mean BMI was 45.4 +/- 6.4 kg/m2.
Mean follow-up was 5.6 (0.5-10.7) years. Complete follow-up was available for 90%
at one year (186/207), 80% at five years (136/171), and 71% at ten years (10/14).
Percentage of excess weight loss at one, five, and ten years was 29.9, 30, and
16.9, respectively. Forty-eight patients (23.1%) required a reoperation. LAGB
failure occurred in 118 (57%) and higher baseline BMI was the only independently
associated factor (OR 1.1; 95%CI 1.0-1.1; p = 0.016). CONCLUSION: LAGB was
associated with poor short and long-term weight loss outcomes and a high failure
rate. With the increased safety profile and greater efficacy of other surgical
techniques, LAGB utilization should be discouraged.
PMID- 28693841
TI - Tattooing improves the detection of small lymph nodes and increases the number of
retrieved lymph nodes in patients with rectal cancer who receive preoperative
chemoradiotherapy: A randomized controlled clinical trial.
AB - BACKGROUND: In rectal cancer who received chemoradiotherapy, the number of Lymph
nodes (LNs) required remains unclear. We conducted a randomized controlled trial
to determine whether preoperative tattooing increases the number of LNs and
enhances the detection rate of metastatic LNs. METHODS: Eighty patients with
rectal cancer who received chemoradiotherapy were randomly assigned to receive no
tattooing (C group) or to receive tattooing (T group). RESULTS: The number of LNs
was significantly higher in the T group (13.3 +/- 7.4, mean +/- SD) than in the C
group (8.8 +/- 5.9, p < 0.001), however, the number of positive LNs did not
differ (0.5 +/- 1.3 vs. 0.5 +/- 1.1, p = 0.882). The long-axis diameter of LNs
was significantly smaller in the T group than in the C group (3.4 +/- 1.8 vs. 3.9
+/- 2.3 mm, p < 0.001), however, the long-axis diameter of positive LNs did not
differ. CONCLUSIONS: Tattooing increased the number of retrieved LNs by 51%,
however, there was no increase in the number of positive LNs.
PMID- 28693842
TI - Sustaining a career in surgery.
AB - Surgery is a demanding career with great rewards and equally great challenges. In
order to sustain our careers as well as the careers of our colleagues, it is
important to understand and address the physical, psychological and spiritual
challenges of surgery. With rare exception, the majority of surgery residents and
practicing surgeons who prematurely leave surgery do so because they find the
work to be physically, emotionally or spiritually incompatible with the vision
they have for their life. Understanding these issues and providing solutions to
improve surgeon wellness can help prevent societal loss of these highly trained
professionals and suffering for surgeons and their families.
PMID- 28693843
TI - Surgical time out: Our counts are still short on racial diversity in academic
surgery.
AB - BACKGROUND: This study provides an updated description of diversity along the
academic surgical pipeline to determine what progress has been made. METHODS:
Data was extracted from a variety of publically available data sources to
determine proportions of minorities in medical school, general surgery training,
and academic surgery leadership. RESULTS: In 2014-2015, Blacks represented 12.4%
of the U.S. population, but only 5.7% graduating medical students, 6.2% general
surgery trainees, 3.8% assistant professors, 2.5% associate professors and 2.0%
full professors. From 2005-2015, representation among Black associate professors
has gotten worse (-0.07%/year, p < 0.01). Similarly, in 2014-2015, Hispanics
represented 17.4% of the U.S. population but only 4.5% graduating medical
students, 8.5% general surgery trainees, 5.0% assistant professors, 5.0%
associate professors and 4.0% full professors. There has been modest improvement
in Hispanic representation among general surgery trainees (0.2%/year, p < 0.01),
associate (0.12%/year, p < 0.01) and full professors (0.13%/year, p < 0.01).
CONCLUSION: Despite efforts to promote diversity in surgery, Blacks and Hispanics
remain underrepresented. A multi-level national focus is imperative to elucidate
effective mechanisms to make academic surgery more reflective of the US
population.
PMID- 28693844
TI - Intrauterine fallopian tube intussusception after vacuum aspiration: Sonographic
features and differential diagnosis.
PMID- 28693845
TI - Highly efficient combustion with low excess air in a modern energy-from-waste
(EfW) plant.
AB - The effect of low excess air and high adiabatic combustion temperatures on CO and
NOx formation has been investigated on a commercially operated energy-from-waste
plant. With optimal combination of low O2 levels and stable combustion control,
uncontrolled NOx levels could be lowered to 100-150mg/Nm3 (dry, at 11% O2) while
keeping CO emissions at low levels. Even at adiabatic temperatures above 1400
degrees C thermal NOx hardly contributed to the total NOx emissions in a grate
fired EfW plant. An advanced combustion control system allowed continuous
operation with very little excess air (lambda<1.2) while keeping CO and NOx at
levels well below the legal emission limits.
PMID- 28693846
TI - Renewed Attention on the Pupil Light Reflex.
AB - In a recent study, Ebitz and Moore described how subthreshold electrical
microstimulation of the macaque frontal eye fields (FEF) modulates the pupillary
light reflex. This elegant study suggests that the influence of the FEF and
prefrontal cortex on attentional modulation of cortical visual processing extends
to the subcortical circuit that mediates a very basic reflex, the pupillary light
reflex.
PMID- 28693847
TI - Cholinergic Control of Information Coding.
AB - Specific forms of firing rate correlations can limit efficient information coding
in neuronal populations. How this is mitigated is an important topic of current
research. A novel study shows that increasing cortical acetylcholine (ACh) levels
alter specific aspects of the population correlation structure, which in turn
improves population-coding abilities.
PMID- 28693848
TI - Does penile tourniquet application alter bacterial adhesion to rat urethral
cells: an in vitro study.
AB - PURPOSE: To investigate the effects of penile tourniquet (PT) application on
bacterial adhesion to urothelium. METHODS: Fifty-six rats were allocated into
control group (CG), sham group (SG), PT group (PTG). No intervention was applied
in CG. A 5mm-length urethral repair was performed in SG and PTG. In PTG, a 10-min
duration of PT was applied during the procedure and the tissue oxygenation
monitor was used to adjust the same degree of ischemia in all subjects. Samples
were examined for wound healing parameters and tissue levels of inflammatory
markers, eNOS, e-selectin, and ICAM-1antibodies. The adhesion of Escherichia coli
to urothelium was investigated with in vitro adhesion assay. RESULTS:
Inflammation was higher and wound healing was worse in SG than CG and in PTG in
comparison to CG and SG (p<0.05). The endothelial damage, as shown by eNOS
expression, was significantly higher in PTG compared to CG and SG (p<0.05). The
staining with ICAM-1 and e-selectin antibodies, showing increased inflammatory
response to bacterial adhesion, was significantly higher in PTG compared to CG
and SG (p<0.05). In vitro urethral cell proliferation was achieved only in CG and
SG revealing significantly increased adhesion in SG compared to CG (p<0.05). The
PT application caused endothelial corruption and prevented cell proliferation in
cell culture. CONCLUSION: The PT application does not improve wound healing and
increases bacterial adhesion molecules in penile tissue. The in vitro assays
showed that PT causes severe endothelial damage and inhibits endothelial cell
proliferation.
PMID- 28693849
TI - Impact of outpatient management following appendectomy for acute appendicitis: An
ACS NSQIP-P analysis.
AB - BACKGROUND: In 2012, a same-day discharge protocol following appendectomy for
acute appendicitis was initiated. Our objective was to determine the success of
the protocol by reviewing the National Surgical Quality Improvement Program
Pediatric (NSQIP-P) outcomes following protocol development. METHODS: The 2015
NSQIP-P Participant Use Data File was queried to identify patients with acute
appendicitis who underwent appendectomy. Outcomes were compared to institutional
outcomes. RESULTS: There were 154 institutional patients and 4973 from NSQIP-P
centers. Institutional rate of outpatient management was higher compared to NSQIP
P (84% vs 48%, p<0.0001). Surgical length of stay was shorter compared to
national rates (0.3+/-0.7 vs 1.1+/-1.9days, p<0.0001). There was no significant
difference in the incidence of superficial (1.9% vs 1.0%, p=0.2), deep (0.6% vs
0.1%, p=0.17) or organ/space surgical site infections (1.3% vs 0.7%, p=0.31). The
incidences of other complications (1.3% vs 0.6%, p=0.26) and 30-day readmissions
(3.2% vs 2.6%, p=0.61) were similar. CONCLUSION: Outpatient management following
appendectomy in children is possible with low morbidity and readmission rates.
Comparison with other NSQIP-Pediatric centers suggests an opportunity to
generalize this practice with considerable savings to the health care system.
LEVEL OF EVIDENCE: Prognosis study, level II.
PMID- 28693850
TI - Early postoperative fever workup in children: utilization and utility.
AB - BACKGROUND: Early postoperative fever is common. Adult data indicate that workup
is unnecessary in the early postoperative period, but comparable data in children
is limited. The objectives are to determine the incidence of fever and the
utilization and yield of tests ordered in children. METHODS: Single-institution,
retrospective analysis of surgical patients undergoing an elective
inpatient/observational surgery between 2011 and 2015 was performed. Early fever
was defined >38.0 degrees C within two days post-procedure. Encounters were
queried for all blood cultures (BC), urinalysis (UA), urine cultures (UC), chest
radiographs (CXR), and respiratory viral panels (RVP) obtained. RESULTS: We
identified 6943 patients, of whom 30.6% developed fever. UA was positive in 19.8%
of patients tested. UC was positive in 15.7% of patients and 92.0% had a urinary
catheter during surgery. BC was positive in 0.69% of patients, all with a central
venous catheter. CXRs were considered infectious in 3.0% of patients tested.
Patients with PICU stay and/or fever >=38.9 degrees C were more likely to undergo
BC and UC, but no more likely to have a positive result compared those without
PICU stay and/or fever <38.9 degrees . CONCLUSION: Early postoperative fever is
common in pediatric surgical populations and rarely associated with an infectious
source. Workup should be applied selectively. LEVEL OF EVIDENCE: Level IV.
PMID- 28693851
TI - A population-based analysis of a rare oncologic entity: Malignant pancreatic
tumors in children.
AB - PURPOSE: To examine the clinicopathological characteristics and prognosis of
pediatric patients with malignant pancreatic tumors in a population-based cohort.
METHODS: The Surveillance, Epidemiology, and End Results (SEER) database was
utilized to identify all pediatric patients with malignant pancreatic tumors,
diagnosed between 1973 and 2013. Kaplan-Meier analysis was performed to determine
median and five-year overall survival (OS) rates. Univariate survival analysis
was executed using the log-rank test. Cox proportional hazards model was used to
identify variables independently associated with mortality. RESULTS: A total of
114 patients with pancreatic malignancies were identified. Median patient age was
16years and the majority of patients were white (64%) females (61.4%). The most
prevalent histologic subtype was neuroendocrine tumors (35.1%), whereas
pancreatoblastoma was more common during the first decade of life (P<0.001).
Distant metastases were noted in 41.7% of the patients, while 33.3% and 25% had
localized and regional disease respectively. Five-year OS rates were 77%, 66.4%
and 64.8% for patients with pancreatoblastoma, neuroendocrine and epithelial
tumors respectively. No death was observed in the solid pseudopapillary tumor
group. Only history of having cancer-directed surgery (CDS) was significantly
associated with lower overall mortality (HR: 5.1, 95% CI: 2.1, 12.4). CONCLUSION:
Pancreatic malignancies are rare in children. Their prognosis is variable and
only CDS was independently associated with superior survival. EVIDENCE
RATING/CLASSIFICATION: Prognosis study, Level II.
PMID- 28693852
TI - Using Simulation to Improve Systems.
AB - Attempts to understand and improve health care delivery often focus on the
characteristics of the patient and the characteristics of the health care
providers, but larger systems surround and integrate with patients and providers.
Components of health care delivery systems can support or interfere with efforts
to provide optimal health care. Simulation in situ, involving real teams
participating in simulations in real care settings, can be used to identify
latent safety threats and improve the work environment while simultaneously
supporting participant learning. Thoughtful planning and skilled debriefing are
essential.
PMID- 28693853
TI - Multidrug therapy for leprosy: a game changer on the path to elimination.
AB - Leprosy is present in more than 100 countries, where it remains a major cause of
peripheral neuropathy and disability. Attempts to eliminate the disease have
faced various obstacles, including characteristics of the causative bacillus
Mycobacterium leprae: the long incubation period, limited knowledge about its
mode of transmission, and its poor growth on culture media. Fortunately, the
leprosy bacillus is sensitive to several antibiotics. The first antibiotic to be
widely used for leprosy treatment was dapsone in the 1950s, which had to be taken
over several years and was associated with increasing bacterial resistance.
Therefore, in 1981, WHO recommended that all registered patients with leprosy
should receive combination therapy with three antibiotics: rifampicin,
clofazimine, and dapsone. Global implementation of this highly effective
multidrug therapy took about 15 years. In 1985, 5.3 million patients were
receiving multidrug therapy; by 1991, this figure had decreased to 3.1 million (a
decrease of 42%) and, by 2000, to 597 232 (a decrease of almost 90%). This
reduction in the number of patients registered for treatment was due to
shortening of the treatment regimen and achievement of 100% coverage with
multidrug therapy. This achievement, which owed much to WHO and the donors of the
multidrug therapy components, prompted WHO in 1991 to set a global target of less
than one case per 10 000 population by 2000 to eliminate the disease as a public
health problem. All but 15 countries achieved this target. Since 2000, about 250
000 new cases of leprosy have been detected every year. We believe an all-out
campaign by a global leprosy coalition is needed to bring that figure down to
zero.
PMID- 28693854
TI - Community transmission of type 2 poliovirus after cessation of trivalent oral
polio vaccine in Bangladesh: an open-label cluster-randomised trial and modelling
study.
AB - BACKGROUND: Trivalent oral polio vaccine (tOPV) was replaced worldwide from
April, 2016, by bivalent types 1 and 3 oral polio vaccine (bOPV) and one dose of
inactivated polio vaccine (IPV) where available. The risk of transmission of type
2 poliovirus or Sabin 2 virus on re-introduction or resurgence of type 2
poliovirus after this switch is not understood completely. We aimed to assess the
risk of Sabin 2 transmission after a polio vaccination campaign with a monovalent
type 2 oral polio vaccine (mOPV2). METHODS: We did an open-label cluster
randomised trial in villages in the Matlab region of Bangladesh. We randomly
allocated villages (clusters) to either: tOPV at age 6 weeks, 10 weeks, and 14
weeks; or bOPV at age 6 weeks, 10 weeks, and 14 weeks and either one dose of IPV
at age 14 weeks or two doses of IPV at age 14 weeks and 18 weeks. After
completion of enrolment, we implemented an mOPV2 vaccination campaign that
targeted 40% of children younger than 5 years, regardless of enrolment status.
The primary outcome was Sabin 2 incidence in the 10 weeks after the campaign in
per-protocol infants who did not receive mOPV2, as assessed by faecal shedding of
Sabin 2 by reverse transcriptase quantitative PCR (RT-qPCR). The effect of
previous immunity on incidence was also investigated with a dynamical model of
poliovirus transmission to observe prevalence and incidence of Sabin 2 virus.
This trial is registered at ClinicalTrials.gov, number NCT02477046. FINDINGS:
Between April 30, 2015, and Jan 14, 2016, individuals from 67 villages were
enrolled to the study. 22 villages (300 infants) were randomly assigned tOPV, 23
villages (310 infants) were allocated bOPV and one dose of IPV, and 22 villages
(329 infants) were assigned bOPV and two doses of IPV. Faecal shedding of Sabin 2
in infants who did not receive the mOPV2 challenge did not differ between
children immunised with bOPV and one or two doses of IPV and those who received
tOPV (15 of 252 [6%] vs six of 122 [4%]; odds ratio [OR] 1.29, 95% CI 0.45-3.72;
p=0.310). However, faecal shedding of Sabin 2 in household contacts was increased
significantly with bOPV and one or two doses of IPV compared with tOPV (17 of 751
[2%] vs three of 353 [1%]; OR 3.60, 95% CI 0.82-15.9; p=0.045). Dynamical
modelling of within-household incidence showed that immunity in household
contacts limited transmission. INTERPRETATION: In this study, simulating 1 year
of tOPV cessation, Sabin 2 transmission was higher in household contacts of mOPV2
recipients in villages receiving bOPV and either one or two doses of IPV, but
transmission was not increased in the community as a whole as shown by the non
significant difference in incidence among infants. Dynamical modelling indicates
that transmission risk will be higher with more time since cessation. FUNDING:
Bill & Melinda Gates Foundation.
PMID- 28693855
TI - High population immunity reduces poliovirus community transmission.
PMID- 28693856
TI - Innovative tools and approaches to end the transmission of Mycobacterium leprae.
AB - Leprosy control has seen little innovation and only limited progress in the past
decade. However, research on the disease has increased and important innovations
are underway. Here, we comment on efforts to develop tools and approaches to
detect leprosy and to stop the transmission of Mycobacterium leprae, the
causative bacillus of the disease. The tracing and screening of contacts of known
patients with leprosy promises to strengthen early diagnosis, while preventive
chemotherapy will reduce the risk of contacts developing the disease by 50-60%
within 2 years of administration. Until now, diagnosis has been mainly based on
the presence of signs and symptoms, but efforts are underway to develop
inexpensive, reliable, point-of-care tests to diagnose infection. Development of
a leprosy-specific vaccine that boosts long-lasting T-cell responses is also a
research objective. As for launching a programme to interrupt transmission, two
interlinked tools-epidemiological modelling and the concept of an investment case
are being developed to explore the feasibility and costs of such a programme and
its overall effect on individuals and society. We believe that sustained
innovation is needed and that only a combination of tools and approaches holds
promise to end M leprae transmission.
PMID- 28693857
TI - How Not To Drown in Data: A Guide for Biomaterial Engineers.
AB - High-throughput assays that produce hundreds of measurements per sample are
powerful tools for quantifying cell-material interactions. With advances in
automation and miniaturization in material fabrication, hundreds of biomaterial
samples can be rapidly produced, which can then be characterized using these
assays. However, the resulting deluge of data can be overwhelming. To the rescue
are computational methods that are well suited to these problems. Machine
learning techniques provide a vast array of tools to make predictions about cell
material interactions and to find patterns in cellular responses. Computational
simulations allow researchers to pose and test hypotheses and perform experiments
in silico. This review describes approaches from these two domains that can be
brought to bear on the problem of analyzing biomaterial screening data.
PMID- 28693858
TI - Plasma in Dentistry: Brief History and Current Status.
AB - We briefly discuss the history of cold atmospheric plasma (CAP) applications in
dentistry. The reasons for seeking innovative solutions in dentistry are
reported, highlighting results showing the potential of plasma along with some
still-open questions. Finally, we suggest the next steps on the road from the
laboratory to the dental chair.
PMID- 28693859
TI - The alpha3beta4 nAChR partial agonist AT-1001 attenuates stress-induced
reinstatement of nicotine seeking in a rat model of relapse and induces minimal
withdrawal in dependent rats.
AB - The strong reinforcing effects of nicotine and the negative symptoms such as
anxiety experienced during a quit attempt often lead to relapse and low success
rates for smoking cessation. Treatments that not only block the reinforcing
effects of nicotine but also attenuate the motivation to relapse are needed to
improve cessation rates. Recent genetic and preclinical studies have highlighted
the involvement of the alpha3, beta4, and alpha5 nicotinic acetylcholine receptor
(nAChR) subunits and the alpha3beta4 nAChR subtype in nicotine dependence and
withdrawal. However, the involvement of these nAChR in relapse is not fully
understood. We previously reported that the alpha3beta4 nAChR partial agonist AT
1001 selectively decreases nicotine self-administration in rats without affecting
food responding. In the present experiments, we examined the efficacy of AT-1001
in attenuating reinstatement of nicotine-seeking behavior in a model of stress
induced relapse. Rats extinguished from nicotine self-administration were treated
with the pharmacological stressor yohimbine prior to AT-1001 treatment and
reinstatement testing. We also examined whether AT-1001 produced any withdrawal
related effects when administered to nicotine-dependent rats. We found that AT
1001 dose-dependently reduced yohimbine stress-induced reinstatement of nicotine
seeking. When administered to nicotine-dependent rats at the dose that
significantly blocked nicotine reinstatement, AT-1001 elicited minimal somatic
withdrawal signs in comparison to the nicotinic antagonist mecamylamine, which is
known to produce robust withdrawal. Our data suggest that alpha3beta4 nAChR
targeted compounds may be a promising approach for nicotine addiction treatment
because they can not only block nicotine's reinforcing effects, but also decrease
motivation to relapse without producing significant withdrawal effects.
PMID- 28693860
TI - Implicit predictions of future rewards and their electrophysiological correlates.
AB - Information that is motivationally relevant to an organism's survival demands
preferential attention. Affective mechanisms facilitate attentional shifts and
potentiate action to allow organisms to respond appropriately to motivationally
relevant information. Previous work has demonstrated that the late-positive
potential (LPP) is an event-related potential elicited by inherently emotional
stimuli. For example, the LPP typically is evoked by images of weapons or
erotica. The present study investigates stimuli that are not inherently
emotional, but that implicitly (without participants' awareness) predict future
monetary gains and losses. Results indicate that, relative to non-predictive
cues, these predictive cues elicited frontally distributed positive potential.
These results suggest that prediction of future rewards evokes neural responses
that are similar to those evoked by inherently emotional stimuli. Results also
indicate that monetary gains and losses elicit a frontally distributed LPP.
PMID- 28693861
TI - Supplementation with zinc in rats enhances memory and reverses an age-dependent
increase in plasma copper.
AB - Zinc and copper are essential trace elements. Dyshomeostasis in these two metals
has been observed in Alzheimer's disease, which causes profound cognitive
impairment. Insulin therapy has been shown to enhance cognitive performance;
however, recent data suggest that this effect may be at least in part due to the
inclusion of zinc in the insulin formulation used. Zinc plays a key role in
regulation of neuronal glutamate signaling, suggesting a possible link between
zinc and memory processes. Consistent with this, zinc deficiency causes cognitive
impairments in children. The effect of zinc supplementation on short- and long
term recognition memory, and on spatial working memory, was explored in young and
adult male Sprague Dawley rats. After behavioral testing, hippocampal and plasma
zinc and copper were measured. Age increased hippocampal zinc and copper, as well
as plasma copper, and decreased plasma zinc. An interaction between age and
treatment affecting plasma copper was also found, with zinc supplementation
reversing elevated plasma copper concentration in adult rats. Zinc
supplementation enhanced cognitive performance across tasks. These data support
zinc as a plausible therapeutic intervention to ameliorate cognitive impairment
in disorders characterized by alterations in zinc and copper, such as Alzheimer's
disease.
PMID- 28693862
TI - Behavioural inflexibility in a comorbid rat model of striatal ischemic injury and
mutant hAPP overexpression.
AB - Alzheimer disease (AD) and stroke coexist and interact; yet how they interact is
not sufficiently understood. Both AD and basal ganglia stroke can impair
behavioural flexibility, which can be reliably modeled in rats using an
established operant based set-shifting test. Transgenic Fischer 344-APP21 rats
(TgF344) overexpress pathogenic human amyloid precursor protein (hAPP) but do not
spontaneously develop overt pathology, hence TgF344 rats can be used to model the
effect of vascular injury in the prodromal stages of Alzheimer disease. We
demonstrate that the injection of endothelin-1 (ET1) into the dorsal striatum of
TgF344 rats (Tg-ET1) produced an exacerbation of behavioural inflexibility with a
behavioural phenotype that was distinct from saline-injected wildtype & TgF344
rats as well as ET1-injected wildtype rats (Wt-ET1). In addition to profiling the
types of errors made, interpolative modeling using logistic exposure-response
regression provided an informative analysis of the timing and efficiency of
behavioural flexibility. During set-shifting, Tg-ET1 committed fewer
perseverative errors than Wt-ET1. However, Tg-ET1 committed significantly more
regressive errors and had a less efficient strategy change than all other groups.
Thus, behavioural flexibility was more vulnerable to striatal ischemic injury in
TgF344 rats.
PMID- 28693863
TI - Effect of ultrasound treatment during osmotic dehydration on bioactive compounds
of cranberries.
AB - The aim of the study was to investigate the influence of ultrasound treatment
applied in osmotic solution on bioactive compounds, such as vitamin C,
polyphenols, anthocyanins and flavonoids content as well as antioxidant activity
in cranberries (Vaccinium oxycoccus). Ultrasound treatment was performed at the
frequency of 21kHz for 30 and 60min in two osmotic solutions - 61.5% sucrose and
30% sucrose with an addition of 0.1% of steviol glycosides. Before the ultrasound
treatment the material was subjected to cutting or blanching. The obtained
results indicated that the influence of ultrasound waves on cranberries depends
on a type of bioactive component. The ultrasound treated cranberries as well as
the ones subjected to cutting or blanching enhanced by ultrasound were
characterized mainly by a lower content of bioactive compounds.
PMID- 28693864
TI - The role of ultrasonic cavitation in refining the microstructure of aluminum
based nanocomposites during the solidification process.
AB - Recent studies showed that the microstructure and mechanical properties of
aluminum based nanocomposites can be significantly improved when ultrasonic
cavitation and solidification processing is used. This is because ultrasonic
cavitation processing plays an important role not only in degassing and
dispersion of the nanoparticles, but also in breaking up the dendritic grains and
refining the as-cast microstructure. In the present study, A356 alloy and Al2O3
nanoparticles are used as the matrix alloy and the reinforcement, respectively.
Nanoparticles were added into the molten A356 alloy and dispersed via ultrasonic
cavitation processing. Ultrasonic cavitation was applied over various temperature
ranges during molten alloy cooling and solidification to investigate the grain
structure formation and the nanoparticle dispersion behavior. Optical Microscopy
and Scanning Electron Microscopy were used to investigate in detail the
differences in the microstructure characteristics and the nanoparticle
distribution. Experimental results indicated that the ultrasonic cavitation
processing and Al2O3 nanoparticles play an important role for microstructure
refinement. In addition, it was shown in this study that the Al2O3 nanoparticles
modified the eutectic phase.
PMID- 28693865
TI - The International Nursing Focus on Mental Health.
PMID- 28693866
TI - Mental Health Needs of Youth in Juvenile Justice: An Executive Summary.
PMID- 28693867
TI - The Correlation Between Schizophrenic Patients' Level of Internalized Stigma and
Their Level of Hope.
AB - AIM: The aim of this study is to determine the correlation between schizophrenic
patients' level of internalized stigma and their level of hope. MATERIAL AND
METHOD: The population of the study consisted of patients who had been diagnosed
with schizophrenia and also met the study inclusion criteria. The study sample
selection from the population was not further divided; the study was conducted
with 76 patients. The data of the study were collected using a personal
information form, the Internalized Stigma of Mental Illness (ISMI) Scale, and
Herth Hope Scale. FINDINGS: The patients' mean score on the Internalized Stigma
Scale was 72.78+/-16.05. Their score on the Hope Scale is 50.36+/-11.91. A
significant negative correlation was found between the total mean scores of ISMI
and the Herth Hope Scale (r=-0.360, p<0.01). A significant positive correlation
was found between the stigma resistance subscale mean score of ISMI and the total
mean score of the Herth Hope Scale (r=0.510, p<0.01). CONCLUSION: The
internalized stigma levels of schizophrenic patients were found to be high,
whereas their hope levels were found to be moderate. A significant negative
correlation was found between internalized stigma and hope. This study also found
a significant positive correlation between the stigma resistance of patients and
their hope levels.
PMID- 28693868
TI - Category 3 and 4 Controlled Drugs Users' Perceptions of Participating in Drug
Abuse-Health Prevention Lectures in Taiwan.
AB - This study was designed to explore Category 3 and 4 controlled drug users'
perceptions of participating in health-prevention lectures. A phenomenological
approach was used. Twelve participants were interviewed after completing the
lectures. Findings revealed five themes (1) mixed emotions; (2) self-development;
(3) finding the lectures lacked practicality and relevance; (4) highlighting
three stages for discontinuing drug-usage; and, (5) suggesting tips for the
advancement of lectures. These findings could be used as a map to help health
professionals understand drug users' perceptions of attending health prevention
lectures and provide insight into how young people might stop using drugs.
PMID- 28693869
TI - Emergency Nursing Experiences in Assisting People With Suicidal Behavior: A
Grounded Theory Study.
AB - AIM: To understand emergency nursing experiences in assisting people with
suicidal behavior. METHOD: Grounded theory study with symbolic interactionism
conducted in 2015 to 2016 in Brazil with 19 nurses. RESULTS: Assistance for
people with suicidal behavior is critical, challenging, evokes different feelings
and requires knowledge, skills and emotional control. Nurses did not feel
prepared or supported, and identified recurrent gaps and problems. Nurses
occupied a limited role, restricted to attending to physical needs. They
predominantly manifested opposition, judgments and incomprehension about
patients. CONCLUSION: This study presents key elements to be addressed in
interventions and investigations regarding nursing support, training and
supervision.
PMID- 28693870
TI - The Impact of Parental Reaction to Sexual Orientation on Depressive Symptoms and
Sexual Risk Behavior Among Hispanic Men Who Have Sex with Men.
AB - PURPOSE: This study examined the relationship of parent reaction to sexual
orientation with depressive symptoms and safer sex among Hispanic adult men who
have sex with men (MSM). We also examined men's acculturation to the U.S.
(Americanism) in relation with these variables. METHOD: Cross-sectional data
collected from July 2011 to December 2012, from 125 MSM with a mean age of
43.02years. Instruments included the Perceived Parent Reaction Scale, the Centers
for Epidemiological Studies Depression Scale, the Safer Sex Behavior
Questionnaire and the Bidimensional Acculturation Scale. Data was analyzed using
Hierarchical generalized linear models (GZLM). RESULTS: Among men whose parents
knew of their sexual orientation, rejection of son's sexual orientation from
mother (p=0.032) and from father (p=0.004) was related to higher number of
depressive symptoms. Parent reactions were not directly related to safer sex
behaviors. Americanism was associated with lower depressive symptoms (p=0.001)
but was not related to safer sex behaviors. CONCLUSIONS: Current parent attitudes
about their sons' sexual orientation had an effect on the sons' emotional
wellbeing and acculturation may play a protective role. Mental health and primary
care clinicians working with Hispanic MSM should assess for level of family
support and provide resources to assist with disclosure and family acceptance of
sexual orientation as indicated, particularly among recently immigrated men who
may be at higher risk.
PMID- 28693871
TI - "It's the First Time I Feel as One". Patients' Experience of Therapeutic Body
Wraps in Swiss Public Adult Inpatient Psychiatric Wards.
AB - Many patients suffering from serious mental illness experience severe anxiety,
and those with psychosis often report feeling that their bodies are falling
apart. Expert opinions reported relational benefits and tranquilizing effects of
therapeutic body wraps (TBWs). Yet this adjunct nursing therapy has rarely been
studied and the existing knowledge is limited to single clinical cases reported
from clinicians' perspectives. This study reports on seven adult patients, whose
independent accounts of TBWs were audio-recorded, transcribed and cross-analyzed.
It sheds light on a commonly underestimated need among many severely ill
psychiatric patients to have their anxiety addressed on a bodily level.
PMID- 28693872
TI - Depression Screening at a Community Health Fair: Descriptives and Treatment
Linkage.
AB - OBJECTIVE: Health fairs are a cost-efficient platform for dissemination of
preventive services to vulnerable populations. Effectiveness of depression
screenings and associated treatment linkage via community health fairs warrants
investigation. METHODS: This study offers the first examination of a depression
screening at a community health fair in 261 adult men (18-87years). The PHQ-9 was
administered via interview by graduate students and on-site psychiatric nurses
were available for a brief consultation for those interested. RESULTS: Over a
quarter of participants screened positive for at least moderate depressive
symptomatology. Of those who screened positive, 35.8% met with an on-site
psychiatric nurse for a consultation. At six-month follow-up, none of the
participants given a referral made an appointment at the community mental health
agency. CONCLUSION: This suggests the importance of providing on-site clinician
consultations at health fairs and the need for a more coordinated system to
schedule future appointments while at the event. IMPACT STATEMENT: Community
health fairs reach vulnerable populations, such as those who are uninsured and
who have not spoken with a professional about mental health concerns. By
conducting depression screening and providing onsite access to a mental health
consultation at community health fairs, participants are better able to identify
their depressive symptoms and are introduced to ways to treat depression.
PMID- 28693873
TI - Development of a Nurse Observation Scale for Inpatients at the Psychiatry Clinic:
Validity and Reliability Study.
PMID- 28693874
TI - The Resilience Questionnaire for Bipolar Disorder: Development and validation.
AB - The goal of this research project was to develop a new questionnaire to assess
resilience in Bipolar Disorder (BD), the Resilience Questionnaire for Bipolar
Disorder (RBD). To examine its psychometric properties, a sample of 125 patients
diagnosed with BD and a comparison sample of 107 people completed the new RBD and
established measures of generic resilience and health-related outcomes.
Exploratory factor analysis for the RBD yielded a 23-item 5-factor solution, and
confirmatory factor analysis indicated adequate fit indices. Internal
consistency, stability, concurrent validation and known-groups' validity were
also supported. The RBD obtained higher responsiveness (6-month follow-up) than
the generic resilience scale (BD sample). The RBD is a robust measure to monitor
resilience in BD.
PMID- 28693875
TI - Diabetes Self-Care Views of Individuals With Severe Mental Illness and Comorbid
Type 2 Diabetes and of Those Only With Type 2 Diabetes.
PMID- 28693876
TI - Effects of a Program to Improve Mental Health Literacy for Married Immigrant
Women in Korea.
AB - This study aimed to develop and evaluate a mental health improvement program for
the acculturative stress and mental health literacy of married immigrant women
using bilingual gatekeepers. Bilingual gatekeepers were recruited from
multicultural centers and trained to provide 8-week structured mental health
improvement services to the women in the experimental group using a mental health
improvement guidebook developed by the authors in 8 different languages. The
program was effective in improving mental health and mental health literacy
scores as well as reducing the degree of acculturative stress. This study offers
a model of effective mental healthcare for multicultural communities.
PMID- 28693877
TI - A Qualitative Study of Barriers to Care for People With Co-Occurring Disorders.
AB - The present qualitative study used face-to-face and telephone interviews with
service providers in the Tampere area in Finland to describe the provider
viewpoint on barriers to care for people with co-occurring disorders. The core
barrier concerns the definition and understanding of the problems: client and
professional perspectives often differ, and both can be out of step with what the
care system actually proposes. Professionals need to take into account contexts
with potentially multiple barriers to care. Providers in each local area should
examine possible barriers and find solutions together, integrating the client
perspective at each step in the process.
PMID- 28693878
TI - Depression and Health-Related Quality of Life and Their Association With
Resourcefulness in Survivors of Prostate Cancer.
AB - OBJECTIVE: This study aimed to identify the determinants of depressive symptoms
(DSs) and health-related quality of life (HRQOL) in survivors of prostate cancer
(PC). METHODS: This study used a descriptive, correlational design to assess a
sample of 133 individuals with PC. The participants were face-to-face interviewed
to collect demographic data and disease characteristics, assess self-control
schedule, and survey health status. Correlation analysis, Student's t-test,
ANOVA, and regression analysis were applied. RESULTS: Over half the patients had
depressive symptoms, and 96.1% had erectile dysfunction. Lack of resourcefulness
was found to decrease PC-specific quality of life (PCQOL) and physical quality of
life (PQOL). The participants who were more resourceful showed a better mental
quality of life (MQOL) and PQOL (r=0.53**; r=0.41**) and fewer DSs (r=-0.52**).
Most participants were stage II and IV, and there were significantly different
effects on PQOL and MQOL related to cancer stage. Regarding the different
outcomes of various therapies, the findings suggested that survivors of PC who
underwent radical prostatectomy were more likely to have a better MQOL than those
who underwent other treatments. In addition, resourcefulness had mediating
effects on pain, PQOL/MQOL, and DSs in the patients with PC. CONCLUSIONS: Good
mental health and resourcefulness can help patients with PC reduce pain and
enhance positive thinking and may augment PQOL and MQOL.
PMID- 28693879
TI - Profiles of the Patient Who Had Compulsory Hospitalization in a District
Psychiatric Hospital.
AB - OBJECTIVE: It aims to examine the profiles of patients who were treated with
compulsory hospitalization between 2011 and 2015 in a district psychiatric
hospital. METHOD: In this retrospective and cohort study, hospital records
gathered from 202 adult patients who were treated with compulsory hospitalization
in units with a bed between 2011 and 2015 in a district psychiatric hospital were
examined. In this study, profiles and socio-demographic features of the patients
with compulsory hospitalization were evaluated by 23 closed-end and open-ended
questions prepared by researchers. In data analysis, Monte Carlo Chi-square test
and number-percentage distribution were used. FINDINGS: 57.4% of examined cases
was female and mean average was 38.88+/-13.06. Of examined cases, 18.8% was
people graduated from high school or university and it was detected that 81.7%
didn't have any regular job during the compulsory hospitalization. Of which 55.9%
has not gotten married and 12.4% was divorced, 48.0% of the population has been
living with their parents, sibling or/and their relatives and 17.8% has been
living alone or in the nursing home. Of which 59.9% of the cases which were
diagnosed with psychosis, 38.1% with psychotic relapse, 22.8% with medication
regulation, 22.8% with excitation (expansiveness) and 15.8% having the risk of
self-mutilation and damage his/her environment were admitted to compulsory
hospitalization. Of these cases, the relative or custodian of 74.2%, employee of
nursing home of 9.4%, law-enforcement officers of 5.4% and medical staff of 4.0%
gave hospitalization approval. While not having any history for alcohol-substance
abuse, it was established that 10.9% of the population had a problematic
juridical records. Of the cases, hospitalization of 75.7% came to end with
recovery/discharge and 20.3% was over with the demand of his/her
relative/custodian, 1.5% of the cases escaped from the hospital. CONCLUSION:
Patients whose majority was female, person who has never gotten married or was
divorced and has low educational level don't have any regular job and live with
their relatives. In addition, their relatives made the majority of these patients
admit to hospital because of the history of psychotic diagnose and psychotic
relapses. According to these results, it is recommended that patients will
receive an effective treatment in order to protect the right to decide their own
treatment.
PMID- 28693880
TI - Postpartum Depression Prevalence and Risk Factors in Turkey: A Systematic Review
and Meta-Analysis.
AB - Postpartum depression (PPD) is a common problem with adverse consequences for the
mother and the infant. This study was performed to determine the prevalence of
and risk factors for PPD in Turkey. In this study, 52 primary studies that were
published between January 1999 and January 2015 were examined. The prevalence of
PPD was determined through a meta-analysis, and the risk factors were determined
through a systematic review. The prevalence of PPD in Turkey was found to be
23.8%. Developed cities had a prevalence of 21.2%, and developing cities had a
prevalence of 25%. Just as throughout the world, PPD is a common problem in
Turkey. It is more prevalent in developing cities. The following factors were the
strongest predictors of postpartum depression: economic status and the employment
status of the spouse, planned pregnancy and having a stressor/illness during
pregnancy, health problems in the newborn, previous psychiatric illness, problems
with family and spouse, reduced social support, and a history of psychiatric
illness in the family.
PMID- 28693881
TI - Outcome Evaluation of an Integrated Treatment for Comorbid Alcohol and Nicotine
Addiction: An Exploratory Study.
PMID- 28693882
TI - Bone Density and Cross-sectional Geometry of the Proximal Femur Are Bilaterally
Elevated in Elite Cricket Fast Bowlers.
AB - The skeleton of a cricket fast bowler is exposed to a unique combination of
gravitational and torsional loading in the form of substantial ground reaction
forces delivered through the front landing foot, and anterior-posterior shear
forces mediated by regional muscle contractions across the lumbo-pelvic region.
The objectives of this study were to compare the hip structural characteristics
of elite fast bowlers with recreationally active age-matched controls, and to
examine unilateral bone properties in fast bowlers. Dual-energy X-ray
absorptiometry of the proximal femur was performed in 26 elite male fast bowlers
and 26 normally active controls. Hip structural analysis (GE Lunar; enCORE
version 15.0) determined areal bone mineral density (BMD) of the proximal femur,
and cross-sectional area, section modulus (Z), cross-sectional moment of inertia,
and femoral strength index at the narrow region of the femoral neck. Mean femoral
neck and trochanter BMD were greater in fast bowlers than in controls (p <0.001).
All bone geometry properties, except for cross-sectional moment of inertia, were
superior in fast bowlers (p <0.05) following adjustment for height and lean mass.
There were no asymmetries in BMD or bone geometry when considering leg dominance
of the fast bowlers (p > 0.05). Elite fast bowlers have superior bone
characteristics of the proximal femur, with results inferring enhanced resistance
to axial compression (cross-sectional area), and bending (Z) forces, and enhanced
strength to withstand a fall impact as indicated by their higher femoral strength
index. No asymmetries in hip bone properties were identified, suggesting that
both torsional and gravitational loading offer significant osteogenic potential.
PMID- 28693883
TI - Reply to Nevens et al.
PMID- 28693884
TI - The flavonoid rutin modulates microglial/macrophage activation to a CD150/CD206
M2 phenotype.
AB - Rutin is a glycosylated flavonoid present in many fruits and plants that has been
demonstrated to have anti-inflammatory and antioxidant properties. However,
little is known about the mechanisms underlying microglial activation and its
effects on the regulation of cytokines and chemokines associated with
inflammatory responses in the central nervous system. In this study we examined
the effect of rutin on resting or lipopolysaccharide (LPS)-stimulated microglia
and characterized their modulation to an activated M1 phenotype or an
alternatively activated M2 phenotype. Microglial cells were treated with rutin (1
100 MUM); alternatively, microglial cells were stimulated with LPS and the cells
were then treated with rutin (50 MUM). The results revealed that rutin treatment
was not toxic to microglial cells and induced a dose-dependent increase in
microglial proliferation associated with changes in morphology after 24 h of
treatment. Rutin also induced microglial activation characterized by an increase
in OX-42 positive cells and a large proportion of cells with a CD150/CD206
positive M2 phenotype. Rutin also induced a decrease in the mRNA levels of TNF,
IL1beta, IL6 and iNOS, reduced the production of IL6, TNF, and nitric oxide, and
increased production of the M2 regulatory cytokine IL10 and arginase. Rutin also
significantly inhibited the LPS-induced expression of PTGS2, IL18 and TGFbeta
mRNA. These findings show that rutin has the ability to promote microglial
proliferation and induces microglial polarization to the M2 profile when cells
are stimulated with LPS. These results point this flavonoid as a possible
alternative in the treatment or prevention of neurodegenerative disorders.
PMID- 28693885
TI - Post-exposure treatment with the oxime RS194B rapidly reverses early and advanced
symptoms in macaques exposed to sarin vapor.
AB - Organophosphate (OP) nerve agents and pesticides trigger a common mechanism of
neurotoxicity resulting from critical targeting and inhibition of
acetylcholinesterases (AChE) in central and peripheral synapses in the
cholinergic nervous system. Therapeutic countermeasures have thus focused on
either administering an oxime post-exposure, that can rapidly reactivate OP
inhibited AChE, or by preventing OP poisoning through administering pre-exposure
treatments that scavenge OPs before they inhibit their physiological AChE
targets. While several pyridinium aldoxime antidotes are currently approved,
their utility is impaired due to their inability to cross the blood-brain barrier
(BBB) efficiently. The present study utilized a macaque (Ma) model to demonstrate
the efficacy of a novel zwitterionic and centrally acting oxime RS194B to
reactivate sarin- and paraoxon-inhibited macaque AChE and butyrylcholinesterase
(BChE) in vitro and to further assess the capacity of RS194B to effect a reversal
of clinical symptoms following sarin inhalation in vivo. In vitro, oxime
reactivation of MaAChE and MaBChE was shown to be comparable to their human
orthologs, while the macaque studies indicated that IM administration of 62.5
mg/kg of RS194B and 0.28 mg/kg atropine after continuous exposure to 49.6 MUg/kg
sarin vapor, rapidly reactivated the inhibited AChE and BChE in blood and
reversed both early and advanced clinical symptoms of sarin-induced toxicity
following pulmonary exposure within 1 h. The rapid cessation of autonomic and
central symptoms, including convulsions, observed in macaques bodes well for the
use of RS194B as an intra- or post-exposure human treatment and validates the
macaque model in generating efficacy and toxicology data required for approval
under the FDA Animal rule.
PMID- 28693886
TI - Investigation of the presence in human urine of mercapturic acids derived from
phenanthrene, a representative polycyclic aromatic hydrocarbon.
AB - Polycyclic aromatic hydrocarbons (PAH) are environmental carcinogens implicated
as causes of cancer in certain industrial settings and in cigarette smokers. PAH
require metabolic activation to exert their carcinogenic effects. One widely
accepted pathway of metabolic activation proceeds through formation of "bay
region" diol epoxides which are highly reactive with DNA and can cause mutations.
Phenanthrene (Phe) is the simplest PAH with a bay region and an excellent model
for the study of PAH metabolism. In previous studies in which [D10]Phe was
administered to smokers, we observed higher levels of [D10]Phe-tetraols derived
from [D10]Phe-diol epoxides in subjects who were null for the glutathione-S
transferase M1 (GSTM1) gene. We hypothesized that Phe-epoxides, the primary
metabolites of Phe, were detoxified by glutathione conjugate formation, which
would result ultimately in the excretion of the corresponding mercapturic acids
in urine. We synthesized the four stereoisomeric mercapturic acids that would
result from attack of glutathione on Phe-epoxides followed by normal processing
of the conjugates. We also synthesized the corresponding dehydrated metabolites
and sulfoxides. These 12 standards were used in liquid chromatography
nanoelectrospray ionization-high resolution tandem mass spectrometry analysis of
urine samples from smokers and creosote workers, the latter exposed to unusually
high levels of PAH. Only the sulfoxide derivatives were consistently detected in
the urine of creosote workers; none of the compounds was detected in the urine of
smokers. These results demonstrate a new pathway of PAH-mercapturic acid
formation, but do not provide an explanation for the role of GSTM1 null status on
Phe-tetraol formation.
PMID- 28693887
TI - Novel 1,2,4-triazole derivatives as antitumor agents against hepatocellular
carcinoma.
AB - Fifteen novel 1,2,3-triazole derivatives were prepared in series of synthetic
steps starting from 4-amino-5-hydrazino-4H-1,2,4-triazole-3-thiol 1. The
structures of the obtained compounds were verified through micoanalytical and
spectral data. All the compounds were screened for their anticancer activity
against liver human cancer cell lines (HEPG2) using Doxorubicin as standard. The
most promising triazolothiadiazine derivative 12 was further tested for its
degree of toxicity by estimating the median lethal dose (LD 50) and its antitumor
activity through inhibiting the angiogenesis and progression of tumor against
diethylnitrosamine (DENA)/CCl4 induced hepatocellular carcinoma (HCC) in rats. To
elucidate its mechanism of action, the following parameters were determined
including: vascular endothelial growth factor (VEGF) as a marker of angiogenesis;
hepatic tyrosine kinase (HTK) as a marker for tumor growth; serum alpha
fetoprotein (AFP) as a marker for hepatocarcinoma; aspartate and alanine
aminotransferases (AST & ALT) as liver function test; malondialdehyde (MDA) and
glutathione (GSH) as markers of antioxidant activity. Liver histopathological
analysis was also evaluated. Carcinogenic rats showed drastic elevation in all
investigated parameters accompanied by reduction in hepatic glutathione.
Administration of compound 12 into rats after induction of experimental HCC,
improved the biochemical changes induced by DENA/CCl4. These observations were
supported by histopathological study of liver sections. It was concluded that
triazolothiadiazine compound 12 could be promising anti HCC agent after more
investigations on higher animals.
PMID- 28693888
TI - Do Patient Expectations Influence Patient-Reported Outcomes and Satisfaction in
Total Hip Arthroplasty? A Prospective, Multicenter Study.
AB - BACKGROUND: The relationship between patient expectations and patient-reported
outcomes (PROs) in total hip arthroplasty (THA) patients is controversial. The
purpose of this study was to examine the impact of preoperative patient
expectations on postoperative PROs and patient satisfaction. METHODS: This was a
prospective multicenter observational cohort study of primary THA patients.
Preoperatively, patients completed Hospital for Special Surgery (HSS) Hip
Replacement Expectations Survey (expectations), 12 item Short Form Survey (SF
12), University of California, Los Angeles (UCLA) activity score, and Hip
Disability and Osteoarthritis Score (HOOS). Postoperatively at 6 months and 1
year, patients completed the Hospital for Special Surgery Hip Replacement
Fulfillment of Expectations Survey (fulfillment of expectations), a satisfaction
survey, and the same PROs as preoperatively. Stepwise multivariate regression
models were created. RESULTS: A total of 207 patients were enrolled. Follow-up
rate was 91% at 6 months and 92% at 1 year. Being employed and lower baseline
HOOS predicted higher expectations (employment status: B = -7.5, P = .002; HOOS:
B = -0.27, P = .002). Higher preoperative expectations predicted greater
improvements in UCLA activity, SF-12 physical component score, and HOOS at 6
months (UCLA activity: B = 0.03, P = .001; SF-12 physical component score: B =
0.15, P = .001; HOOS: B = 0.20; P = .008) and UCLA activity at 1 year (B = 0.02,
P = .004). Furthermore, higher expectations predicted higher postoperative
satisfaction and fulfillment of expectations at 6 months (satisfaction: B = 0.21,
P < .001; fulfillment of expectations: B = 0.30, P < .001) and higher fulfillment
of expectations at 1 year (B = 0.17, P = .006). CONCLUSION: In patients
undergoing THA, being employed and worse preoperative hip function predict of
higher preoperative expectations of surgery. Higher expectations predict greater
improvement in PROs, greater patient satisfaction, and the fulfillment of
expectations. These findings can be used to guide patient counseling and shared
decision making preoperatively.
PMID- 28693889
TI - Barefoot Doctors and the "Health Care Revolution" in Rural China: A Study
Centered on Shandong Province.
AB - Barefoot doctors were rural medical personnel trained en masse, whose emergence
and development had a particular political, economic, social, and cultural
background. Like the rural cooperative medical care system, the barefoot doctor
was a well-known phenomenon in the Cultural Revolution. Complicated regional
differences and a lack of reliable sources create much difficulty for the study
of barefoot doctors and result in differing opinions of their status and
importance. Some scholars greatly admire barefoot doctors, whereas others harshly
criticize them. This paper explores the rise and development of barefoot doctors
based on a case study of Shandong province. I argue that the promotion of
barefoot doctors was a consequence of the medical education revolution and an
implementation of the Cultural Revolution in rural public health care, which
significantly influenced medical services and development in rural areas. First,
barefoot doctors played a significant role in accomplishing the first rural
health care revolution by providing primary health care to peasants and
eliminating endemic and infectious illnesses. Second, barefoot doctors were the
agents who integrated Western and Chinese medicines under the direction of the
state. As an essential part of the rural cooperative medical system, barefoot
doctor personnel grew in number with the system's implementation. After the
Cultural Revolution ended, the cooperative medical system began to disintegrate-a
process that accelerated in the 1980s until the system's collapse in the wake of
the de-collectivization. As a result, the number of barefoot doctors also ran
down steadily. In 1985, "barefoot doctor" as a job title was officially removed
from Chinese medical profession, demonstrating that its practice was non
universal and unsustainable.
PMID- 28693890
TI - Artemisinin and Chinese Medicine as Tu Science.
AB - The story of discovery of artemisinin highlights the diversity of scientific
values across time and space. Resituating artemisinin research within a broader
temporal framework allows us to understand how Chinese drugs like qinghao came to
articulate a space for scientific experimentation and innovation through its
embodiment of alternating clusters of meanings associated with tu and yang within
scientific discourse. Tu science, which was associated with terms like native,
Chinese, local, rustic, mass, and crude, articulated a radical vision of science
in the service of socialist revolutionary ideals. Yang science, which signified
foreign, Western, elite, and professional, tended to bear the hallmarks of
professionalism, transnational networks in education and training, and an
emphasis on basic or foundational research. With respect to medical research, the
case of artemisinin highlights how the constitution of socialist science as an
interplay of tu and yang engendered different scientific values and parameters
for scientific endeavor. Modern medical research in Maoist China could harness
the productive energies of mass participation to technical expertise in its
investigations of Chinese drugs, and under the banner of tu science, it became
possible and scientifically legitimate to research Chinese drugs in ways that had
previously provoked resistance and controversy.
PMID- 28693891
TI - An alarming trend: Change in the risk profile of patients with ST elevation
myocardial infarction over the last two decades.
AB - BACKGROUND: Coronary artery disease (CAD) is the leading cause of mortality
around the world. We sought to study changes in the risk profile of patients
presenting with ST elevation myocardial infarction (STEMI). METHODS: We
retrospectively studied all patients presenting with STEMI to our center between
1995 and 2014. Patients were divided into four quartiles, 5years each. Baseline
risk factors and comorbidities were recorded. Sub-analysis was done for patients
with established CAD and their household incomes. RESULTS: A total of 3913
patients (67.9% males) were included; 42.5% presented with anterior STEMI and
57.5% inferior STEMI. Ages were 64+/-12, 62+/-13, 61+/-13 and 60+/-13 in the four
quartiles respectively. Obesity prevalence was 31, 37, 38 and 40% and diabetes
mellitus prevalence was 24, 25, 24 and 31%, while hypertension was 55, 67, 70 and
77%, respectively, p<0.01 for all. Smoking prevalence was 28, 32, 42 and 46,
p<0.01. When subgroup analysis was done for patients with history of CAD,
prevalence of smoking, obesity, diabetes and hypertension significantly increased
across the four quartiles. When patients were divided to four groups based on
household income (poor, low middle, middle and high income), prevalence of
diabetes, hypertension, smoking and obesity were significantly higher in patients
with low income. CONCLUSION: Despite better understanding of cardiovascular risk
factors and more focus on preventive cardiology, patients presenting with STEMI
over the past 20years are getting younger and more obese, with more prevalence of
smoking, hypertension, and diabetes mellitus. This trend is greater in the lower
income population.
PMID- 28693892
TI - The application of decellularized human term fetal membranes in tissue
engineering and regenerative medicine (TERM).
AB - Tissue engineering and regenerative medicine (TERM) is a field that applies
biology and engineering principles to "restore, maintain or repair a tissue after
injury". Besides the potential to treat various diseases, these endeavours
increase our understanding of fundamental cell biology. Although TERM has
progressed rapidly, engineering a whole organ is still beyond our skills,
primarily due to the complexity of tissues. Material science and current
manufacturing methods are not capable of mimicking this complexity. Therefore,
many researchers explore the use of naturally derived materials that maintain
important biochemical, structural and mechanical properties of tissues.
Consequently, employing non-cellular components of tissues, particularly the
extracellular matrix, has emerged as an alternative to synthetic materials.
Because of their complexity, decellularized tissues are not as well defined as
synthetic materials but they provide cells with a microenvironment that resembles
their natural niche. Decellularized tissues are produced from a variety of
sources, among which the fetal membranes are excellent candidates since their
supply is virtually unlimited, they are readily accessible with minimum ethical
concerns and are often discarded as a biological waste. In this review, we will
discuss various applications of decellularized fetal membranes as substrates for
the expansion of stem cells, their use as two and three-dimensional scaffolds for
tissue regeneration, and their use as cell delivery systems. We conclude that
fetal membranes have great potential for use in TERM.
PMID- 28693894
TI - Letter to the editor regarding: Rat model of chronic tympanic membrane
perforation: Ventilation tube with mitomycin C and dexamethasone.
PMID- 28693893
TI - Emerging role for dysregulated decidualization in the genesis of preeclampsia.
AB - In normal human placentation, uterine invasion by trophoblast cells and
subsequent spiral artery remodeling depend on cooperation among fetal
trophoblasts and maternal decidual, myometrial, immune and vascular cells in the
uterine wall. Therefore, aberrant function of anyone or several of these cell
types could theoretically impair placentation leading to the development of
preeclampsia. Because trophoblast invasion and spiral artery remodeling occur
during the first half of pregnancy, the molecular pathology of fetal placental
and maternal decidual tissues following delivery may not be informative about the
genesis of impaired placentation, which transpired months earlier. Therefore, in
this review, we focus on the emerging prospective evidence supporting the concept
that deficient or defective endometrial maturation in the late secretory phase
and during early pregnancy, i.e., pre-decidualization and decidualization,
respectively, may contribute to the genesis of preeclampsia. The first
prospectively-acquired data directly supporting this concept were unexpectedly
revealed in transcriptomic analyses of chorionic villous samples (CVS) obtained
during the first trimester of women who developed preeclampsia 5 months later.
Additional supportive evidence arose from investigations of Natural Killer cells
in first trimester decidua from elective terminations of women with high
resistance uterine artery indices, a surrogate for deficient trophoblast
invasion. Last, circulating insulin growth factor binding protein-1, which is
secreted by decidual stromal cells was decreased during early pregnancy in women
who developed preeclampsia. We conclude this review by making recommendations for
further prospectively-designed studies to corroborate the concept of endometrial
antecedents of preeclampsia. These studies could also enable identification of
women at increased risk for developing preeclampsia, unveil the molecular
mechanisms of deficient or defective (pre)decidualization, and lead to
preventative strategies designed to improve (pre)decidualization, thereby
reducing risk for preeclampsia development.
PMID- 28693895
TI - Determination of the Accuracy of 5 Electronic Apex Locators in the Function of
Different Employment Protocols.
AB - INTRODUCTION: The aim of this study was to evaluate the accuracy of 5 electronic
apex locators (EALs): Root ZX II (RZX; J Morita, Tokyo, Japan), Raypex 6 (RAY;
VDW GmbH, Munich, Germany), Apex ID (AID; SybronEndo, Orange, CA), Propex II
(PRO; Dentsply Maillefer, Ballaigues, Switzerland), and Propex Pixi (PIXI,
Dentsply Maillefer) when used in the following protocols: (1) -1.0, insertion up
to 1.0 mm below the apical foramen (AF); (2) 0.0/-1.0, insertion until the AF and
withdrawn 1.0 mm short of the AF; (3) 0.0, insertion until the AF; and (4)
over/0.0, insertion until "over" and withdrawal to AF. METHODS: Thirty human
lower premolars had coronary accesses and cervical and middle thirds preparations
performed, allowing AF standardization (200 MUm). Using an alginate experimental
model, root canal length (RCL) measurements were performed sequentially with EALs
following each of the protocols. RESULTS: Considering the suggested protocols,
the lowest mean error values were observed in 0.0, 0.10 mm (RZX), 0.13 mm (RAY),
0.16 mm (AID), 0.23 mm (PRO), and 0.10 mm (PIXI), without a significant
difference for over/0.0 (P > .05). Comparing the results obtained in 0.0 with
those found in -1.0 and 0.0/-1.0, significant differences were observed for most
EALs (P < .05). For the comparison between EALs, significant differences were
observed only in protocols -1.0 and over/0.0 (P < .05). CONCLUSIONS: Under the
conditions of the study, it was concluded that, regardless of the mechanism of
the device, the best results were found when electronic RCL measurement was
performed at the AF; furthermore, the electronic withdrawal did not offer any
additional advantage over the reach of the AF.
PMID- 28693896
TI - Crucial motifs and residues in the extracellular loops influence the formation
and specificity of connexin docking.
AB - Most of the early studies on gap junction (GJ) channel function and docking
compatibility were on rodent connexins, while recent research on GJ channels
gradually shifted from rodent to human connexins largely due to the fact that
mutations in many human connexin genes are found to associate with inherited
human diseases. The studies on human connexins have revealed some key differences
from those found in rodents, calling for a comprehensive characterization of
human GJ channels. Functional studies revealed that docking and formation of
functional GJ channels between two hemichannels are possible only between docking
compatible connexins. Two groups of docking-compatible rodent connexins have been
identified. Compatibility is believed to be due to their amino acid residue
differences at the extracellular loop domains (E1 and E2). Sequence alignment of
the E1 and E2 domains of all connexins known to make GJs revealed that they are
highly conserved and show high sequence identity with human Cx26, which is the
only connexin with near atomic resolution GJ structure. We hypothesize that
different connexins have a similar structure as that of Cx26 at the E1 and E2
domains and use the corresponding residues in their E1 and E2 domains for
docking. Based on the Cx26 GJ structure and sequence analysis of well-studied
connexins, we propose that the E1-E1 docking interactions are staggered with each
E1 interacting with two E1s on the docked connexon. The putative E1 docking
residues are conserved in both docking-compatible and -incompatible connexins,
indicating that E1 does not likely serve a role in docking compatibility.
However, in the case of E2-E2 docking interactions, the putative docking residues
are only conserved within the docking-compatible connexins, suggesting the E2 is
likely to serve the function of docking compatibility. Docking compatibility
studies on human connexins have attracted a lot of attention due to the fact that
putative docking residues are mutational hotspots for several connexin-linked
human diseases. This article is part of a Special Issue entitled: Gap Junction
Proteins edited by Jean Claude Herve.
PMID- 28693897
TI - Connexins, important players in the dissemination of prostate cancer cells.
AB - Over the past 50years, increasing experimental evidences have established that
connexins (Cxs) and gap junctional intercellular communication (GJIC) ensure an
important role in both the onset and development of cancerous processes. In the
present review, we focus on the impact of Cxs and GJIC during the development of
prostate cancer (PCa), from the primary growth mainly localized in acinar glands
and ducts to the distant metastasis mainly concentrated in bone. As observed in
several other types of solid tumours, Cxs and especially Cx43 exhibit an
ambivalent role with a tumour suppressor effect in the early stages and,
conversely, a rather pro-tumoural profile for most of invasion and dissemination
steps to secondary sites. We report here the current knowledge on the function of
Cxs during PCa cells migration, cytoskeletal dynamics, proteinases activities and
the cross talk with the surrounding stromal cells in the microenvironment of the
tumour and the bones. In addition, we discuss the role of Cxs in the bone tropism
even if the prostate model is rarely used to study the complete sequence of
cancer dissemination compared to breast cancer or melanoma. Even if not yet fully
understood, these recent findings on Cxs provide new insights into their
molecular mechanisms associated with progression and bone targeted behaviour of
PCa. This article is part of a Special Issue entitled: Gap Junction Proteins
edited by Jean Claude Herve.
PMID- 28693898
TI - Nanosecond pulsed electric fields depolarize transmembrane potential via voltage
gated K+, Ca2+ and TRPM8 channels in U87 glioblastoma cells.
AB - Nanosecond pulsed electric fields (nsPEFs) have a variety of applications in the
biomedical and biotechnology industries. Cancer treatment has been at the
forefront of investigations thus far as nsPEFs permeabilize cellular and
intracellular membranes leading to apoptosis and necrosis. nsPEFs may also
influence ion channel gating and have the potential to modulate cell physiology
without poration of the membrane. This phenomenon was explored using live cell
imaging and a sensitive fluorescent probe of transmembrane voltage in the human
glioblastoma cell line, U87 MG, known to express a number of voltage-gated ion
channels. The specific ion channels involved in the nsPEF response were screened
using a membrane potential imaging approach and a combination of pharmacological
antagonists and ion substitutions. It was found that a single 10ns pulsed
electric field of 34kV/cm depolarizes the transmembrane potential of cells by
acting on specific voltage-sensitive ion channels; namely the voltage and Ca2+
gated BK potassium channel, L- and T-type calcium channels, and the TRPM8
transient receptor potential channel.
PMID- 28693899
TI - Porosity and pore size distribution in a sedimentary rock: Implications for the
distribution of chlorinated solvents.
AB - Characterizing properties of the rock matrix that control retention and release
of chlorinated solvents is essential in evaluating the extent of contamination
and the application of remediation technologies in fractured rock. Core samples
from seven closely spaced boreholes in a mudstone subject to trichloroethene
(TCE) contamination were analyzed using Mercury Intrusion Porosimetry to
investigate porosity and pore size distribution as a function of mudstone
characteristics, and depth and lateral extent in the aquifer; organic carbon
content was also evaluated to identify the potential for adsorption. Porosity and
retardation factor varied over two orders of magnitude, with the largest
porosities and largest retardation factors associated with carbon-rich mudstone
layers. Larger porosities were also measured in the shallow rock that has been
subject to enhanced groundwater flow. Porosity also varied over more than an
order of magnitude in spatially continuous mudstone layers. The analyses of the
rock cores indicated that the largest pore diameters may be accessible to entry
of the nonaqueous form of TCE. Although the porosity associated with the largest
pore diameters is small (~0.1%), that volume of TCE can significantly affect the
total TCE that is retained in the rock matrix. The dimensions of the largest pore
diameters may also be accessible to microbes responsible for reductive
dechlorination; however, the small percentage of the pore space that can
accommodate microbes may limit the extent of reductive dechlorination in the rock
matrix.
PMID- 28693900
TI - Biodegradation of pharmaceuticals and endocrine disruptors with oxygen, nitrate,
manganese (IV), iron (III) and sulfate as electron acceptors.
AB - Biodegradation of pharmaceuticals and endocrine disrupting compounds was examined
in long term batch experiments for a period of two and a half years to obtain
more insight into the effects of redox conditions. A mix including lipid lowering
agents (e.g. clofibric acid, gemfibrozil), analgesics (e.g. diclofenac,
naproxen), beta blockers (e.g. atenolol, propranolol), X-ray contrast media (e.g.
diatrizoic acid, iomeprol) as well as the antiepileptic carbamazepine and
endocrine disruptors (e.g. bisphenol A, 17alpha-ethinylestradiol) was analyzed in
batch tests in the presence of oxygen, nitrate, manganese (IV), iron (III), and
sulfate. Out of the 23 selected substances, 14 showed a degradation of >50% of
their initial concentrations under aerobic conditions. The beta blockers
propranolol and atenolol and the analgesics pentoxifylline and naproxen showed a
removal of >50% under anaerobic conditions. In particular naproxen proved to be
degradable with oxygen and under most anaerobic conditions, i.e. with manganese
(IV), iron (III), or sulfate. The natural estrogens estriol, estrone and 17beta
estradiol showed complete biodegradation under aerobic and nitrate-reducing
conditions, with a temporary increase of estrone during transformation of estriol
and 17beta-estradiol. Transformation of 17beta-estradiol under Fe(III)-reducing
conditions resulted in an increase of estriol as well. Concentrations of
clofibric acid, carbamazepine, iopamidol and diatrizoic acid, known for their
recalcitrance in the environment, remained unchanged.
PMID- 28693901
TI - Reply to letter: Response to the letter "Anaesthesia management of accidental
extubation in the prone position".
PMID- 28693902
TI - Medication errors: A challenge for anesthesiology.
PMID- 28693903
TI - Effectiveness of long-term vortioxetine treatment of patients with major
depressive disorder.
AB - To investigate the effectiveness, safety, and tolerability of vortioxetine in
patients treated at therapeutic doses (5-20mg/day) for both acute and maintenance
treatment, patient-level data were pooled from 5 long-term (52-week), open-label
extension studies of major depressive disorder. The mean (+/-standard deviation)
MADRS total score improved from 17.1+/-10.2 at the start of maintenance therapy
to 7.6+/-8.2 (observed cases [OC]) or 10.3+/-9.9 (last observation carried
forward [LOCF]) at week 52. The mean HAM-A total scores improved from 11.3+/-6.9
to 6.0+/-6.0 (OC) or 7.5+/-6.7 (LOCF) and the mean CGI-S score improved from
3.11+/-1.20 to 1.94+/-1.08 (OC) or 2.27+/-1.26 (LOCF) at week 52. Response and
remission rates increased over time. At week 52, the total response rate was
75.4% (n=916/1215, LOCF) and the total remission rate was 60.7% (n=738/1215,
LOCF). There were no differences in effectiveness as assessed by MADRS total
scores at week 52 in subgroups based on gender, age (<55 vs >=55 years), baseline
HAM-A total score (<20 vs >=20), baseline MADRS total score (<30 vs >=30),
previous major depressive episodes (MDEs) (<3 vs >=3) or current MDE duration (<6
vs >=6 months) at the start of the lead-in studies, or response status (>=50%
decrease in MADRS total score during the lead-in study). The most commonly
reported adverse event during the maintenance period was nausea.
PMID- 28693904
TI - Corrigendum to "Dietary Allium hookeri reduces inflammatory response and
increases expression of intestinal tight junction proteins in LPS-induced young
broiler chicken" [Res. Vet. Sci. 112:149-155].
PMID- 28693905
TI - A Temporal and Spatial Analysis Approach to Automated Segmentation of Microbubble
Signals in Contrast-Enhanced Ultrasound Images: Application to Quantification of
Active Vascular Density in Human Lower Limbs.
AB - Contrast-enhanced ultrasound (CEUS) using microbubble contrast agents has shown
great promise in visualising and quantifying active vascular density. Most
existing approaches for vascular density quantification using CEUS are calculated
based on image intensity and are susceptible to confounding factors and imaging
artefact. Poor reproducibility is a key challenge to clinical translation. In
this study, a new automated temporal and spatial signal analysis approach is
developed for reproducible microbubble segmentation and quantification of
contrast enhancement in human lower limbs. The approach is evaluated in vitro on
phantoms and in vivo in lower limbs of healthy volunteers before and after
physical exercise. In this approach, vascular density is quantified based on the
relative areas microbubbles occupy instead of their image intensity. Temporal
features of the CEUS image sequences are used to identify pixels that contain
microbubble signals. A microbubble track density (MTD) measure, the ratio of the
segmented microbubble area to the whole tissue area, is calculated as a surrogate
for active capillary density. In vitro results reveal a good correlation (r2 =
0.89) between the calculated MTD measure and the known bubble concentration. For
in vivo results, a significant increase (129% in average) in the MTD measure is
found in lower limbs of healthy volunteers after exercise, with excellent
repeatability over a series of days (intra-class correlation coefficient = 0.96).
This compares to the existing state-of-the-art approach of destruction and
replenishment analysis on the same patients (intra-class correlation coefficient
<=0.78). The proposed new approach shows great potential as an accurate and
highly reproducible clinical tool for quantification of active vascular density.
PMID- 28693906
TI - Reproducible Computer-Assisted Quantification of Myocardial Perfusion with
Contrast-Enhanced Ultrasound.
AB - Myocardial perfusion can be quantified by myocardial contrast echocardiography
(MCE) and is used for the diagnosis of coronary artery disease (CAD). However,
existing MCE quantification software is highly operator dependent and has poor
reproducibility and ease of usage. The aim of this study was to develop robust
and easy-to-use software that can perform MCE quantification accurately,
reproducibly and rapidly. The developed software has the following features: (i)
semi-automatic segmentation of the myocardium; (ii) automatic rejection of MCE
data with poor image quality; (iii) automatic computation of perfusion parameters
such as myocardial blood flow (MBF). MCE sequences of 18 individuals (9 normal, 9
with CAD) undergoing vasodilator stress with dipyridamole were analysed
quantitatively using the software. When evaluated against coronary angiography,
the software achieved a sensitivity of 71% and a specificity of 91% for hyperemic
MBF. With the automatic rejection algorithm, the sensitivity and specificity
further improved to 77% and 94%, respectively. For MBF reproducibility, the
percentage agreement is 85% (kappa = 0.65) for inter-observer variability and 88%
(kappa = 0.72) for intra-observer variability. The intra-class correlation
coefficients are 0.94 (inter-observer) and 0.96 (intra-observer). The time taken
to analyse one MCE sequence using the software is about 3 min on a PC. The
software has exhibited good diagnostic performance and reproducibility for CAD
detection and is rapid and user-friendly.
PMID- 28693907
TI - Histopathology of viral infections of the lung.
PMID- 28693908
TI - Pathology of pulmonary tuberculosis and non-tuberculous mycobacterial lung
disease: Facts, misconceptions, and practical tips for pathologists.
AB - Most pathologists are familiar with the microscopic features of tuberculosis and
the need to examine special stains for acid-fast bacteria (AFB) in cases of
granulomatous lung disease. However, misconceptions do exist, including the
concept that finding AFB in "caseating granulomas" confirms the diagnosis of
tuberculosis. This dogma is attributable to the high prevalence of tuberculosis
in many countries, as well as unfamiliarity with the microscopic spectrum of non
tuberculous mycobacterial lung disease. This review aims to provide surgical
pathologists with practical tips to identify AFB, illustrate the histologic
overlap between pulmonary tuberculosis and non-tuberculous mycobacterial lung
disease, and highlight the importance of cultures in this setting. M.
tuberculosis and non-tuberculous mycobacteria cannot be reliably differentiated
either on the basis of the tissue reaction or by bacterial morphology on acid
fast stains. Although a presumptive clinical diagnosis of tuberculosis can be
made without culture-confirmation, the only definitive means to determine the
true identity of AFB is by cultures or molecular methods. Making this distinction
is most critical when AFB are found in incidentally detected lung nodules in
geographic locations where the incidence of tuberculosis is low, because in such
settings AFB in necrotizing granulomas of the lung are more likely to be non
tuberculous mycobacteria than M. tuberculosis.
PMID- 28693909
TI - Synthesis and evaluation of 1-phenyl-1H-1,2,3-triazole-4-carboxylic acid
derivatives as xanthine oxidase inhibitors.
AB - This study mainly focused on the modification of the X2 position in febuxostat
analogs. A series of 1-phenyl-1H-1,2,3-triazole-4-carboxylic acid derivatives (1a
s) with an N atom occupying the X2 position was designed and synthesized.
Evaluation of their inhibitory potency in vitro on xanthine oxidase indicated
that these compounds exhibited micromolar level potencies, with IC50 values
ranging from 0.21uM to 26.13MUM. Among them, compound 1s (IC50=0.21MUM) showed
the most promising inhibitory effects and was 36-fold more potent than
allopurinol, but was still 13-fold less potent than the lead compound Y-700,
which meant that a polar atom fused at the X2 position could be unfavorable for
potency. The Lineweaver-Burk plot revealed that compound 1s acted as a mixed-type
xanthine oxidase inhibitor. Analysis of the structure-activity relationships
demonstrated that a more lipophilic ether tail (e.g., meta-methoxybenzoxy) at the
4'-position could benefit the inhibitory potency. Molecular modeling provided a
reasonable explanation for the structure-activity relationships observed in this
study.
PMID- 28693910
TI - Antileishmanial potential of fused 5-(pyrazin-2-yl)-4H-1,2,4-triazole-3-thiols:
Synthesis, biological evaluations and computational studies.
AB - A series of newer 1,2,4-triazole-3-thiol derivatives 5(a-m) and 6(a-i) containing
a triazole fused with pyrazine moiety of pharmacological significance have been
synthesized. All the synthesized compounds were screened for their in vitro
antileishmanial and antioxidant activities. Compounds 5f (IC50=79.0uM) and 6f
(IC50=79.0uM) were shown significant antileishmanial activity when compared with
standard sodium stibogluconate (IC50=490.0uM). Compounds 5b (IC50=13.96uM) and 6b
(IC50=13.96uM) showed significant antioxidant activity. After performing
molecular docking study and analyzing overall binding modes it was found that the
synthesized compounds had potential to inhibit L. donovani pteridine reductase 1
enzyme. In silico ADME and metabolic site prediction studies were also held out
to set an effective lead candidate for the future antileishmanial and
antibacterial drug discovery initiatives.
PMID- 28693911
TI - [Technique of complex mammary irradiation: Mono-isocentric 3D conformational
radiotherapy and helical tomotherapy].
AB - PURPOSE: To evaluate the dosimetric contribution of helical tomotherapy for
breast cancers compared with conformal radiotherapy in mono-isocentric technique.
PATIENTS AND METHOD: For 23 patients, the dosimetric results in mono-isocentric
3D conformational radiotherapy did not satisfy the constraints either of target
volumes nor organs at risk. A prospective dosimetric comparison between mono
isocentric 3D conformational radiotherapy and helical tomotherapy was therefore
carried out. RESULTS: The use of helical tomotherapy showed a benefit in these 23
patients, with either an improvement in the conformity index or homogeneity, but
with an increase in low doses. Of the 23 patients, two had pectus excavatum, five
had past thoracic irradiation and two required bilateral irradiation. The other
14 patients had a combination of morphology and/or indication of lymph node
irradiation. For these patients, helical tomotherapy was therefore preferred to
mono-isocentric 3D conformational radiotherapy. CONCLUSIONS: Tomotherapy appears
to provide better homogeneity and tumour coverage. This technique of irradiation
may be justified in the case of morphological situations such as pectus exavatum
and in complex clinical situations. In other cases, conformal radiotherapy in
mono-isocentric technique remains to be favoured.
PMID- 28693912
TI - Spheno-occipital synchondrosis: Examining the degree of fusion in a South African
Black skeletal sample.
AB - Estimating age-at-death is one of the many biological demographics that a
forensic anthropologist needs to determine for a set of unknown skeletal remains.
A useful skeletal developmental marker, which can aid in estimating age in sub
adult remains, is the state of fusion of the spheno-occipital synchondrosis. This
study aimed to determine the repeatability of a three-stage scoring method and
the age at which the spheno-occipital synchondrosis begins and completes fusion
in a Black South African sample. A total of 147 male and female skeletal
individuals aged between 12-30 years from the Raymond A. Dart Collection of Human
Skeletons were included. The mean age-at-death noted for the commencement of
fusion at the spheno-occipital synchondrosis was 16.2 (+/-2.9) years in females
and 16.7 (+/-1.2) years in males, with females displaying signs of fusion taking
place approximately three years before their male counterparts. Complete fusion
of this skeletal developmental marker was observed in 100% of the sample over the
age of 20 years, regardless of sex. A Kappa value of 1.0 was achieved when the
repeatability and reproducibility of the three-stage scoring method was tested.
Complete fusion of this synchondrosis occurred slightly later in this South
African sample than that noted in previous literature. This finding may be
attributed to the differences in health and socio-economic statuses between these
different population groups, reiterating the need for population-specific data to
be developed. The importance of noting the state of fusion of the spheno
occipital synchondrosis during the examination of relevant forensic cases may aid
in the formation of a narrower age-at-death range for sub-adult and young adult
skeletal remains.
PMID- 28693913
TI - From Sea to Bloodstream: Vibrio vulnificus Sepsis.
PMID- 28693914
TI - Targeting progesterone metabolism in breast cancer with l-proline derived new 14
azasteroids.
AB - Breast cancer cell proliferation is promoted by a variety of mitogenic signals.
Classically estrogen is considered as most predominant mitogenic signal in
hormone-dependent breast cancer and progesterone is primarily considered to have
protective effect. However, it is suggested that some progesterone metabolite may
promote breast cancer and progesterone metabolites like 5alpha-pregnane and 4
pregnene could serve as regulators of estrogen-responsiveness of breast cancer
cells. Here, we estimated the potential of alternate targeting of breast cancer
via progesterone signalling. l-Proline derived novel 14-azasteroid compounds were
screened against MCF-7 and MDA-MB-231 cell lines using MTT assay. In silico
studies, cell cycle, Annexin-V-FITC/PI, JC-1 mitochondrial assay, ROS analysis
were performed to analyse the impact of hit compound 3b on breast cancer cells.
Further, we analysed the impact of hit 3b on the progesterone, its metabolites
and enzymes responsible for the conversion of progesterone and its metabolites
using ELISA. Data suggests that compound 3b binds and down regulates of 5alpha
reductase by specifically inhibiting production of progesterone metabolites that
are capable of promoting breast cancer proliferation, epithelial mesenchymal
transition and migration. This study establishes the proof of concept and
generation of new leads for additional targeting of breast cancer.
PMID- 28693915
TI - Selective opioid growth factor receptor antagonists based on a stilbene isostere.
AB - As part of an ongoing drug development effort aimed at selective opioid receptor
ligands based on the pawhuskin natural products we have synthesized a small set
of amide isosteres. These amides were centered on lead compounds which are
selective antagonists for the delta and kappa opioid receptors. The amide isomers
revealed here show dramatically different activity from the parent stilbene
compounds. Three of the isomers synthesized showed antagonist activity for the
opioid growth factor (OGF)/opioid growth factor receptor (OGFR) axis which is
involved in cellular and organ growth control. This cellular signaling mechanism
is targeted by "low-dose" naltrexone therapy which is being tested clinically for
multiple sclerosis, Crohn's disease, cancer, and wound healing disorders. The
compounds described here are the first selective small molecule ligands for the
OGF/OGFR system and will serve as important leads and probes for further study.
PMID- 28693916
TI - Phosphonodifluoropyruvate is a mechanism-based inhibitor of phosphonopyruvate
decarboxylase from Bacteroides fragilis.
AB - Bacteroides fragilis, a human pathogen, helps in the formation of intra-abdominal
abscesses and is involved in 90% of anaerobic peritoneal infections.
Phosphonopyruvate decarboxylase (PnPDC), a thiamin diphosphate (ThDP)-dependent
enzyme, plays a key role in the formation of 2-aminoethylphosphonate, a component
of the cell wall of B. fragilis. As such PnPDC is a possible target for
therapeutic intervention in this, and other phosphonate producing organisms.
However, the enzyme is of more general interest as it appears to be an
evolutionary forerunner to the decarboxylase family of ThDP-dependent enzymes. To
date, PnPDC has proved difficult to crystallize and no X-ray structures are
available. In the past we have shown that ThDP-dependent enzymes will often
crystallize if the cofactor has been irreversibly inactivated. To explore this
possibility, and the utility of inhibitors of phosphonate biosynthesis as
potential antibiotics, we synthesized phosphonodifluoropyruvate (PnDFP) as a
prospective mechanism-based inhibitor of PnPDC. Here we provide evidence that
PnDFP indeed inactivates the enzyme, that the inactivation is irreversible, and
is accompanied by release of fluoride ion, i.e., PnDFP bears all the hallmarks of
a mechanism-based inhibitor. Unfortunately, the enzyme remains refractive to
crystallization.
PMID- 28693917
TI - Biocatalysts for the pharmaceutical industry created by structure-guided directed
evolution of stereoselective enzymes.
AB - Enzymes have been used for a long time as catalysts in the asymmetric synthesis
of chiral intermediates needed in the production of therapeutic drugs. However,
this alternative to man-made catalysts has suffered traditionally from distinct
limitations, namely the often observed wrong or insufficient enantio- and/or
regioselectivity, low activity, narrow substrate range, and insufficient
thermostability. With the advent of directed evolution, these problems can be
generally solved. The challenge is to develop and apply the most efficient
mutagenesis methods which lead to highest-quality mutant libraries requiring
minimal screening. Structure-guided saturation mutagenesis and its iterative form
have emerged as the method of choice for evolving stereo- and regioselective
mutant enzymes needed in the asymmetric synthesis of chiral intermediates. The
number of (industrial) applications in the preparation of chiral pharmaceuticals
is rapidly increasing. This review features and analyzes typical case studies.
PMID- 28693918
TI - In Reply to 'Detection of Urate Crystals in Kidney Tissue'.
PMID- 28693919
TI - Detection of Urate Crystals in Kidney Tissue.
PMID- 28693920
TI - S100B promotes injury-induced vascular remodeling through modulating smooth
muscle phenotype.
AB - S100B is a biomarker of nervous system injury, but it is unknown if it is also
involved in vascular injury. In the present study, we investigated S100B function
in vascular remodeling following injury. Balloon injury in rat carotid artery
progressively induced neointima formation while increasing S100B expression in
both neointimal vascular smooth muscle (VSMC) and serum along with an induction
of proliferating cell nuclear antigen (PCNA). Knockdown of S100B by its shRNA
delivered by adenoviral transduction attenuated the PCNA expression and
neointimal hyperplasia in vivo and suppressed PDGF-BB-induced VSMC proliferation
and migration in vitro. Conversely, overexpression of S100B promoted VSMC
proliferation and migration. Mechanistically, S100B altered VSMC phenotype by
decreasing the contractile protein expression, which appeared to be mediated by
NF-kappaB activity. S100B induced NF-kappaB-p65 gene transcription, protein
expression and nuclear translocation. Blockade of NF-kappaB activity by its
inhibitor reversed S100B-mediated downregulation of VSMC contractile protein and
increase in VSMC proliferation and migration. It appeared that S100B regulated NF
kappaB expression through, at least partially, the Receptor for Advanced
Glycation End products (RAGE) because RAGE inhibitor attenuated S100B-mediated NF
kappaB promoter activity as well as VSMC proliferation. Most importantly, S100B
secreted from VSMC impaired endothelial tube formation in vitro, and knockdown of
S100B promoted re-endothelialization of injury-denuded arteries in vivo. These
data indicated that S100B is a novel regulator for vascular remodeling following
injury and may serve as a potential biomarker for vascular damage or drug target
for treating proliferative vascular diseases.
PMID- 28693921
TI - Effects of couple based coping intervention on self-efficacy and quality of life
in patients with resected lung cancer.
AB - OBJECTIVE: We aimed to assess the couple based coping intervention (CBCI) for
self-efficacy and quality of life in patients with resected lung cancer, compared
with individual coping intervention (ICI). METHODS: From October to December
2015, 132 consecutive patients with resected lung cancer who were married/lived
in a stable relationship were randomly assigned to the ICI group and the CBCI
group. RESULTS: The CBCI group had higher GSES compared with the ICI group at 2
month after operation, and at 6 month after operation (P<0.05). The CBCI group
had higher VT, SF, RE, and MH score of SF-36 compared with the ICI group at 2
month after operation, and at 6 month after operation (P<0.05), but no
significant differences were found in RP, PF, BP, and GH score of SF-36 compared
between two groups (P>0.05) in these 2 time points. CONCLUSION: Couple based
coping intervention is more effective than individual coping intervention for
improving the self-efficacy and the quality of life in patients with resected
lung cancer. PRACTICE IMPLICATIONS: Practitioners might like to consider using
couple based coping intervention strategy to improve self-efficacy and quality of
life in patients with resected lung cancer.
PMID- 28693922
TI - Shared decision-making and outcomes in type 2 diabetes: A systematic review and
meta-analysis.
AB - OBJECTIVE: Type 2 diabetes is a chronic disease which necessitates the
development of a therapeutic alliance between patient and provider. This review
systematically examines the association between treatment shared decision-making
(SDM) and outcomes in diabetes. METHODS: A range of bibliographic databases and
gray literature sources was searched. Included studies were subjected to dual
data extraction and quality assessment. Outcomes were synthesized using meta
analyses where reporting was sufficiently homogenous or alternatively synthesized
in narrative fashion. RESULTS: The search retrieved 4592 records, which were
screened by title, abstract, and full text to identify 16 studies with a range of
study designs and populations. We found evidence of an association between SDM
and improved decision quality, patient knowledge and patient risk perception. We
found little evidence of an association between SDM and glycemic control, patient
satisfaction, quality of life, medication adherence or trust in physician.
CONCLUSIONS: This work elucidates the potential clinical utility of SDM
interventions in the management of Type 2 Diabetes and helps inform future
research on the topic. PRACTICE IMPLICATIONS: A more complete understanding of
the associations between SDM and outcomes will guide and motivate efforts aimed
at improving uptake of the SDM paradigm.
PMID- 28693923
TI - Diverse functions of the prion protein - Does proteolytic processing hold the
key?
AB - Proteolytic processing of the cellular and disease-associated form of the prion
protein leads to generation of bioactive soluble prion protein fragments and
modifies the structure and function of its cell-bound form. The nature of
proteases responsible for shedding, alpha-, beta-, and gamma-cleavage of the
prion protein are only partially identified and their regulation is largely
unknown. Here, we provide an overview of the increasingly multifaceted picture of
prion protein proteolysis and shed light on physiological and pathological roles
associated with these cleavages. This article is part of a Special Issue
entitled: Proteolysis as a Regulatory Event in Pathophysiology edited by Stefan
Rose-John.
PMID- 28693924
TI - Site-1 protease and lysosomal homeostasis.
AB - The Golgi-resident site-1 protease (S1P) is a key regulator of cholesterol
homeostasis and ER stress responses by converting latent transcription factors
sterol regulatory element binding proteins (SREPBs) and activating transcription
factor 6 (ATF6), as well as viral glycoproteins to their active forms. S1P is
also essential for lysosome biogenesis via proteolytic activation of the
hexameric GlcNAc-1-phosphotransferase complex required for modification of newly
synthesized lysosomal enzymes with the lysosomal targeting signal, mannose 6
phosphate. In the absence of S1P, the catalytically inactive alpha/beta-subunit
precursor of GlcNAc-1-phosphotransferase fails to be activated and results in
missorting of newly synthesized lysosomal enzymes, and lysosomal accumulation of
non-degraded material, which are biochemical features of defective GlcNAc-1
phosphotransferase subunits and the associated pediatric lysosomal diseases
mucolipidosis type II and III. The early embryonic death of S1P-deficient mice
and the importance of various S1P-regulated biological processes, including
lysosomal homeostasis, cautioned for clinical inhibition of S1P. This article is
part of a Special Issue entitled: Proteolysis as a Regulatory Event in
Pathophysiology edited by Stefan Rose-John.
PMID- 28693925
TI - A "Ct contrast"-based strain-specific real-time quantitative PCR system for
Lactobacilllus paracasei subsp. paracasei NTU 101.
AB - BACKGROUND/PURPOSES: Routine cell number determination for specific Lactobacillus
strain by cultivation requires at least 4-7 days. Thus rapid and specific cell
number determine methods such as strain-specific quantitative PCR (qPCR) are
valuable. However, qPCR method is vulnerable to difficult PCR target such as
dimer/secondary structure forming sequence. METHODS: In this study, a two
component, "Ct contrast" approach was applied to strain-specific qPCR system
following the development of Lactobacillus paracasei subsp. paracasei NTU 101
(NTU 101) strain-specific PCR with random amplification of polymorphic DNA (RAPD)
derived strain-specific sequences. RESULTS: The quantitative range of the NTU 101
strain-specific qPCR system was 3.0 * 101 to 3.0 * 105 copies for pure cultures,
and 3.0 * 102 to 3.0 * 105 copies for multi-strain or unknown food samples. The
results of spike in test and real sample testing suggested that non-specific weak
background signals did not compromise test specificity, and demonstrated the
potential of the NTU 101 strain-specific qPCR system in food samples. CONCLUSION:
The two-component, "Ct contrast" approach is useful for qPCR discrimination when
no ideal PCR target is available or the variance of the target site is
unpredictable. The Ct contrast approach might provide a simple and robust
solution for other challenging qPCR targets.
PMID- 28693926
TI - High in vitro activity of fidaxomicin against Clostridium difficile isolates from
a university teaching hospital in China.
AB - BACKGROUND: Clostridium difficile infection (CDI) is a significant cause of
morbidity and mortality in both the acute care setting and the wider healthcare
system. The purpose of this study was to evaluate the in vitro activity of
fidaxomicin against C. difficile isolates from a university teaching hospital in
China. METHODS: One hundred and one C. difficile isolates were collected and
analyzed for toxin genes by multiplex PCR. The toxin gene positive strains were
also typed by multilocus sequence typing (MLST) and PCR-ribotyping. The MICs of
the isolates were determined against fidaxomicin, metronidazole, vancomycin,
tigecycline and moxifloxacin, by the agar dilution method. RESULTS: All the 101
isolates exhibited low MICs to fidaxomicin (0.032-1 mg/L), metronidazole (0.125-1
mg/L), vancomycin (0.25-2 mg/L) and tigecycline (0.016-0.5 mg/L). Tigecycline
showed the lowest geometric mean MIC value (0.041 mg/L), followed by fidaxomicin
(0.227 mg/L), metronidazole (0.345 mg/L), and vancomycin (0.579 mg/L). About 35%
of the strains (n = 35) were resistant to moxifloxacin, and the resistance rate
to moxifloxacin for A-B+CDT- isolates (85.0%) was much higher than that of
A+B+CDT- (15.7%) and A-B-CDT- (29.2%) isolates (P < 0.001). The MIC values of
fidaxomicin, metronidazole, vancomycin and moxifloxacin against the 3 ST1
isolates were higher than for other STs. All the 28 moxifloxacin-resistant
toxigenic isolates carried a mutation either in gyrA or/and gyrB. CONCLUSION:
Fidaxomicin exhibited high antimicrobial activity against all C. difficile
isolates tested, which shows promise as a new drug for treating Chinese CDI
patients.
PMID- 28693927
TI - Risk factors and outcomes of cerebrospinal fluid overdrainage in HIV-negative
patients with cryptococcal meningitis after the ventriculoperitoneal shunting
procedure.
AB - PURPOSE: Shunt procedures used to treat cryptococcal meningitis complicated with
hydrocephalus and/or increased intracranial pressure (IICP) could result in
cerebrospinal fluid (CSF) overdrainage, thereby presenting therapeutic
challenges. METHODS: We analyzed the clinical features and neuroimaging findings
after the ventriculoperitoneal (VP) shunt procedure in 51 HIV (Human
Immunodeficiency Virus)-negative patients with cryptococcal meningitis, to assess
the risk factors associated with post-shunt CSF overdrainage. RESULTS:
Symptomatic CSF overdrainage occurred in 12% (6/51) of patients with cryptococcal
meningitis who underwent the shunt procedure. Rapid deterioration of neurological
conditions was found in 6 patients after the shunt procedure was performed,
including disturbed consciousness, quadriparesis, and dysphasia in 5 patients and
severe ataxia in 1. The mean duration of CSF overdrainage after the shunting
procedure was 2-7 days (mean 4 days). The mean interval between meningitis onset
to shunting procedure remained independently associated with CSF overdrainage,
and the cut-off value for predicting CSF overdrainage in interval between
meningitis onset to shunting procedure was 67.5 days. CONCLUSIONS: CSF
overdrainage after the VP shunt procedure is not rare, especially in patients
with a high-risk of cryptococcal meningitis who also have a prolonged duration of
hydrocephalus and/or IICP.
PMID- 28693928
TI - The different modes of binding of the dust mite allergens, Der f 7 and Der p 7,
on a monoclonal antibody WH9 contribute to the differential reactivity.
AB - BACKGROUND: Der f 7 and Der p 7 are important house dust mite allergens. An IgE
binding inhibition monoclonal antibody WH9 reacts ten folds stronger against Der
p 7 than to Der f 7. The purpose of this study is to identify the antigenic
determinant(s) and the structural basis of Der f 7 recognize by WH9. METHODS: WH9
reactive determinant(s) on Der f 7 was identified by immunoblot and immunoblot
inhibition. The 3-D binary complex structures of WH9 and the group 7 allergens
were simulated with homology modeling and docking methods. RESULTS: WH9 reacted
with the Der f 7 f9 fragment. Among the five site-directed Der f 7 mutants, WH9
showed reduced immunoblot reactivity against Der f 7 S156A, D159A and P160A
mutants. Only the wild-type protein and the Der f 7 I157A and L158A mutants can
inhibit significantly the WH9-binding against Der f 7. The structural model of
the Der f 7-WH9 complex suggests residues S156 and D159 of Der f 7 can bind to
WH9 via potential hydrogen bonds. CONCLUSION: The structure models of Der f 7-WH9
and Der p 7-WH9 complexes revealed that the differential modes of binding of Der
p 7 and Der f 7 allergens on WH9 contribute to the differential reactivity of WH9
against the Der f 7 and the Der p 7 mite allergens.
PMID- 28693929
TI - Impact of broad-spectrum antimicrobial treatment on the ecology of intestinal
flora.
AB - BACKGROUND: Suppression of intestinal flora by broad-spectrum antimicrobial
agents facilitated risk of colonization or infection with resistant pathogen. We
aimed to investigate the changes in bowel carriage of target resistant
microorganisms (TRO) among patients treated with three different classes of
Pseudomonas-sparing broad-spectrum antimicrobial agents (ertapenem, moxifloxacin
and flomoxef) with anaerobic coverage. Risk factors for developing colonization
of TRO were also analyzed. METHODS: We prospectively enrolled the adult
hospitalized patients (>20 years old) who were indicated for at least 7-day
course with either of ertapenem, moxifloxacin or flomoxef. Rectal swabs were
performed for the patients who received at least 1-day course of study
antibiotics during the treatment duration. The TROs included Pseudomonas
aeruginosa, Enterobacteriaceae, and Acinetobacter baumannii. MacConkey agars with
study antibiotics were used to isolate the TROs and evaluate the antimicrobial
resistance. RESULTS: The mean age of our study population was 61.6 years, and
58.8% were males. The rates of rectal colonization for Pseudomonas aeruginosa was
similar among the study medications (ertapenem 13.2%, flomoxef 20%, moxifloxacin
14.3%, p = 0.809). Compared with ertapenem, flomoxef (odds ratio [OR], 4.30; 95%
confidence interval [95% CI], 1.28-14.48, p = 0.019) and moxifloxacin (OR, 6.95;
95% CI, 1.36-35.52, p = 0.019) had higher risk for colonization of ertapenem
resistant Escherichia coli colonization. CONCLUSION: The patients who received
treatment of ertapenem may have a lower risk of rectal colonization for ertapenem
resistant Escherichia coli than those who received flomoxef or moxifloxacin. The
rate of Pseudomonas colonization did not differ between the three study
Pseudomonas-sparing agents.
PMID- 28693930
TI - The prevalence of rectal carriage of Klebsiella pneumoniae amongst diabetic
patients and their clinical relevance in Taiwan: A five-year prospective study.
AB - BACKGROUND/PURPOSE: Pyogenic liver abscess (PLA) and bacteremia caused by
Klebsiella pneumoniae is a common complication among patients with diabetes
mellitus (DM). The aim of this study is to investigate the prevalence of rectal
carriage and serotype distribution of K. pneumoniae amongst DM patients and their
clinical relevance. METHODS: We prospectively collected rectal swabs for K.
pneumoniae culture in asymptomatic DM patients from March 2008 to June 2009.
Seven capsular serotypes that were commonly associated with PLA were determined
by capsular polysaccharide synthesis (cps) genotyping. Microbiologically
confirmed bacterial infections were evaluated 1 and 5 years after initial
enrolment of the patients. RESULTS: A total of 100 male and 62 female patients
(mean age, 56.6 years) were enrolled. Of these, 77 (47.5%) had rectal K.
pneumoniae colonization. Colonizers were older than non-colonizers (p = 0.03).
Sex, fasting blood glucose, and initial HbA1C were not statistically different (p
= 0.26, 0.18, and 0.31, respectively). Among the 65 available isolates, 22
(33.8%) belonged to the seven main serotypes. During the 5-year's follow-up, 21
patients developed microbiologically documented bacterial infections but none of
them developed PLA and bacteremia. Risk factors for bacterial infection within 5
years included initial glycosylated hemoglobin (HbA1C) > 10% or first-year
average HbA1C > 10%. CONCLUSION: Although nearly half of asymptomatic DM patients
had rectal carriage of K. pneumoniae and one-third of them colonized by isolates
belonging to the seven serotypes related to PLA, none of them subsequently
developed PLA and colonized patients did not have higher risk of
microbiologically confirmed bacterial infections.
PMID- 28693931
TI - Maintenance of Drug-Eluting Stent Patency Through Use of a Cangrelor Infusion in
the Clinical Setting of Massive Pulmonary Hemorrhage and Venoarterial
Extracorporeal Membrane Oxygenation.
PMID- 28693932
TI - Muscle Tissue Saturation Compared With Muscle Tissue Perfusion During Low Blood
Flows: An Experimental Study.
AB - OBJECTIVE: To investigate whether changes in muscle tissue perfusion measured
with positron emission tomography would be reflected by parallel changes in
muscle tissue oxygen saturation (StO2) measured using near-infrared spectroscopy
during high and low blood flow levels achieved using cardiopulmonary bypass (CPB)
in an animal model. DESIGN: A prospective, randomized study. SETTING: Research
laboratory, single institution. PARTICIPANTS: Eight pigs (69-71 kg).
INTERVENTIONS: In anesthetized pigs, normothermic CPB was established with a
blood flow of 60 mL/kg/min for 1 hour. Thereafter, a low blood flow of either
47.5 or 35 mL/kg/min was applied for 1 hour followed by a blood flow of 60
mL/kg/min for an additional hour. Regional StO2 was measured continuously by
placing a near-infrared spectroscopy electrode on the skin above the gracilis
muscle of the noncannulated back leg. Muscle tissue perfusion was measured using
positron emission tomography with 15O-labeled water during spontaneous
circulation and the different CPB blood flows. Systemic oxygen consumption was
estimated by measurement of venous saturation and lactate levels. MEASUREMENTS
AND MAIN RESULTS: The results showed profound systemic ischemia during low CPB
blood flow. StO2 remained high until muscle tissue perfusion decreased to about
50%, after which StO2 paralleled the linear decrease in muscle tissue perfusion.
CONCLUSION: In an experimental CPB animal model, StO2 was stable until muscle
tissue perfusion was reduced by about 50%, and at lower blood flow levels, there
was almost a linear relationship between StO2 and muscle tissue perfusion.
PMID- 28693933
TI - "Partially Matched" US Senior Diagnostic Radiology Applicants: Scope of the
Problem and Implications for Applicants, Residency Training Programs, and the
Academic Diagnostic Radiology Community.
AB - RATIONALE AND OBJECTIVES: Anecdotal reports have recently surfaced of an increase
in the number of US senior diagnostic radiology (DR)-bound residency applicants
who did not secure a preliminary year position through the Main Resident Match
(the Match) of the National Resident Matching Program (NRMP), so-called "partial
matches." This study sought to determine the scope of this phenomenon and address
potential causes and solutions. MATERIALS AND METHODS: Publicly available and
proprietary data from the National Resident Matching Program were analyzed from
2005-2016 to determine the number of partially matched US senior applicants,
selectivity of DR residency training, availability of preliminary year positions,
number of unique preliminary year applicants, distribution of preliminary year
matches by successfully matched applicants in relevant specialties (DR,
anesthesiology, dermatology, neurology, physical medicine and rehabilitation, and
radiation oncology), and percentage of categorical training programs
participating in the Match. RESULTS: Since 2012, there has been a trend toward an
increase in the number of partially matched US senior DR applicants, with a
transitory recovery in the 2015 Match. Although possible explanations for this
increase are proposed, a definitive etiology remains elusive. Strategies to
offset this phenomenon include advising perceived at-risk applicants to apply
more broadly to preliminary year positions, creating more categorical training
positions, abolishing the preliminary year requirement, and drawing high-caliber
medical students to the field. CONCLUSIONS: Although a definitive explanation for
a recent increase in partial matches remains elusive, strategies exist for DR
applicants, residency programs, and the DR academic community to minimize this
risk.
PMID- 28693934
TI - Frailty in Older Adults Undergoing Aortic Valve Replacement: The FRAILTY-AVR
Study.
AB - BACKGROUND: Frailty is a geriatric syndrome that diminishes the potential for
functional recovery after a transcatheter aortic valve replacement (TAVR) or
surgical aortic valve replacement (SAVR) procedure; however, its integration in
clinical practice has been limited by a lack of consensus on how to measure it.
OBJECTIVES: This study sought to compare the incremental predictive value of 7
different frailty scales to predict poor outcomes following TAVR or SAVR.
METHODS: A prospective cohort of older adults undergoing TAVR or SAVR was
assembled at 14 centers in 3 countries from 2012 to 2016. The following frailty
scales were compared: Fried, Fried+, Rockwood, Short Physical Performance
Battery, Bern, Columbia, and the Essential Frailty Toolset (EFT). Outcomes of
interest were all-cause mortality and disability 1 year after the procedure.
RESULTS: The cohort was composed of 1,020 patients with a median age of 82 years.
Depending on the scale used, the prevalence of frailty ranged from 26% to 68%.
Frailty as measured by the EFT was the strongest predictor of death at 1 year
(adjusted odds ratio [OR]: 3.72; 95% confidence interval [CI]: 2.54 to 5.45) with
a C-statistic improvement of 0.071 (p < 0.001) and integrated discrimination
improvement of 0.067 (p < 0.001). Moreover, the EFT was the strongest predictor
of worsening disability at 1 year (adjusted OR: 2.13; 95% CI: 1.57 to 2.87) and
death at 30 days (adjusted OR: 3.29; 95% CI: 1.73 to 6.26). CONCLUSIONS: Frailty
is a risk factor for death and disability following TAVR and SAVR. A brief 4-item
scale encompassing lower-extremity weakness, cognitive impairment, anemia, and
hypoalbuminemia outperformed other frailty scales and is recommended for use in
this setting. (Frailty Assessment Before Cardiac Surgery & Transcatheter
Interventions; NCT01845207).
PMID- 28693935
TI - The Core Curriculum.
PMID- 28693936
TI - Sirenomelia associated with discoid adrenal and lumbar meningocoele: An autopsy
report.
AB - Mermaid syndrome or Sirenomelia is a rare congenital deformity in which the legs
are fused and bears resemblance to mermaid's tail. It carries a poor prognosis,
due to associated urogenital and gastrointestinal abnormalities. An early
antenatal diagnosis using Magnetic Resonance Imaging (MRI) can help in
termination of pregnancy. Embryologically, it is considered as the extreme form
of caudal regression syndrome due to the persistence of vitelline artery. Here,
we report a case of Sirenomelia associated with bilateral renal agenesis along
with the rare findings of discoid adrenal, lumbar meningocoele and abnormalities
of the hand.
PMID- 28693937
TI - Spermatogenic dynamics of the spiny rat Kannabateomys amblyonyx (Wagner, 1845)
(Rodentia, Echimyidae).
AB - Rodents are distributed worldwide, playing important ecological roles regarding
preservation of forest areas. Thus, the study of their reproductive biology is a
key for conservation initiatives that prevent extinction and/or improve species
management. The present study aimed to describe the spermatogenic dynamics of the
spiny rat Kannabateomys amblyonyx, an endemic species from Atlantic Rainforest
areas, in Brazil. The average body weight was 418.43g with a gonadosomatic index
of 0.41%. The testicular parenchyma organization followed the pattern described
for other rodent species, with a large amount of seminiferous tubules occupying
93.57% of the organ, in a total of 26.04m per testicle. Stage I of the
seminiferous tubule cycle was the most frequent in K. amblyonyx, while stage IV
the most scarce. Each tubular section in stage I showed 0.47 type-A
spermatogonia, 11.78 primary spermatocytes in pre-leptotene, 3.81 in zygotene and
14.31 in pachytene, whereas 32.19 cells were round spermatids and 6.23 were
Sertoli cells. From these results it was possible to determine the sperm reserve
of 274.49*106 cells per gram of testis. The mitotic and meiotic indexes were
25.06 and 2.25 cells, respectively, whereas the spermatogenic yield was 69.73
cells. Those findings are significant since this is the first study regarding the
reproductive aspects of the only Echimyidae species in Brazil, which shows a
monogamous mating system.
PMID- 28693938
TI - Will Retzius-sparing Prostatectomy Be the Future of Prostate Cancer Surgery?
PMID- 28693939
TI - Reply to Julie Steinestel, Christof Bernemann, Andres J. Schrader, and Jochen K.
Lennerz's Letter to the Editor re: Emmanuel S. Antonarakis, Changxue Lu, Brandon
Luber, et al. Clinical Significance of Androgen Receptor Splice Variant-7 mRNA
Detection in Circulating Tumor Cells of Men with Metastatic Castration-resistant
Prostate Cancer Treated with First- and Second-line Abiraterone and Enzalutamide.
J Clin Oncol 2017;35:2149-56. AR-V7 Testing: What's in it for the Patient?:
Estimating the Clinical Utility of Blood-based AR-V7 Testing in Prostate Cancer.
PMID- 28693940
TI - Parkinson's in the oldest old: Impact on estimates of future disease burden.
AB - BACKGROUND: Traditionally the risk of Parkinson's has been considered to increase
monotonically with age, although there is evidence that prevalence and incidence
may decrease in the oldest old. To examine this further we estimated the national
prevalence and incidence of Parkinson's in New Zealand, using drug-tracing
methods, to examine the relationship of Parkinson's with sex and age up to 100+.
METHODS: Information on Parkinson's-related medications was extracted from the
national pharmaceutical database of community-dispensed medications from 2005 to
2014. Diagnoses for a large subset of individuals were independently determined
through national mortality and hospital admissions datasets. We used a Bayesian
model, accommodating diagnostic uncertainty and bias, to estimate the number of
people with Parkinson's. RESULTS: The 2013 prevalence of Parkinson's in New
Zealand was 210 per 100 000 population (95% uncertainty interval 208-212) with
age-standardized prevalence rates higher for males (ratio 1.6:1). Incidence was
31 per 100 000 person-years (95% uncertainty interval 30-32), also higher in
males (ratio 1.8:1). Incidence and prevalence by age increased exponentially
until 75 years, peaked at 85 years, and then dropped sharply. CONCLUSIONS: The
prevalence of Parkinson's in New Zealand is expected to double over a 25-year
period but then increase at a slower rate due to the drop-off in prevalence and
incidence in the oldest old. The findings suggest that Parkinson's disease is not
an aging-dependent but an age-dependent disorder.
PMID- 28693941
TI - An evaluation of medication reconciliation at an outpatient Internal Medicines
clinic.
PMID- 28693942
TI - A man with syncope.
PMID- 28693943
TI - A man with generalized weakness.
PMID- 28693944
TI - A bullous enigma.
PMID- 28693945
TI - Swelling of distal extremities with peripheral blood eosinophilia in a young
Asian woman.
PMID- 28693946
TI - Corrigendum to "Age estimation by an analysis of spheno-occipital synchondrosis
using cone-beam computed tomography" [Legal Med. (Tokyo) 18 (2016) 13-19].
PMID- 28693947
TI - Synchrotron radiation MUCT and histology evaluation of bone-to-implant contact.
AB - The purpose of this study was to evaluate bone-to-implant contact (BIC) in two
dimensional (2D) histology compared to high-resolution three-dimensional (3D)
synchrotron radiation micro computed tomography (SR micro-CT). High spatial
resolution, excellent signal-to-noise ratio, and contrast establish SR micro-CT
as the leading imaging modality for hard X-ray microtomography. Using SR micro-CT
at voxel size 5 MUm in an experimental goat mandible model, no statistically
significant difference was found between the different treatment modalities nor
between recipient and reconstructed bone. The histological evaluation showed a
statistically significant difference between BIC in reconstructed and recipient
bone (p < 0.0001). Further, no statistically significant difference was found
between the different treatment modalities which we found was due to large
variation and subsequently due to low power. Comparing histology and SR micro-CT
evaluation a bias of 5.2% was found in reconstructed area, and 15.3% in recipient
bone. We conclude that for evaluation of BIC with histology and SR micro-CT, SR
micro-CT cannot be proven more precise than histology for evaluation of BIC,
however, with this SR micro-CT method, one histologic bone section is comparable
to the 3D evaluation. Further, the two methods complement each other with
knowledge on BIC in 2D and 3D.
PMID- 28693948
TI - The American Society of Clinical Oncology 2017 Annual Meeting: A review and
summary of selected abstracts.
PMID- 28693949
TI - Composting of food wastes: Status and challenges.
AB - This review analyses the main challenges of the process of food waste composting
and examines the crucial aspects related to the quality of the produced compost.
Although recent advances have been made in crucial aspects of the process, such
composting microbiology, improvements are needed in process monitoring.
Therefore, specific problems related to food waste composting, such as the
presence of impurities, are thoroughly analysed in this study. In addition,
environmental impacts related to food waste composting, such as emissions of
greenhouse gases and odours, are discussed. Finally, the use of food waste
compost in soil bioremediation is discussed in detail.
PMID- 28693950
TI - Enhanced volatile fatty acids production from anaerobic fermentation of food
waste: A mini-review focusing on acidogenic metabolic pathways.
AB - Recently, efficient disposal of food waste (FW) with potential resource recovery
has attracted great attentions. Due to its easily biodegradable nature, rich
nutrient availability and high moisture content, FW is regarded as favorable
substrate for anaerobic digestion (AD). Both waste disposal and energy recovery
can be fulfilled during AD of FW. Volatile fatty acids (VFAs) which are the
products of the first-two stages of AD, are widely applied in chemical industry
as platform chemicals recently. Concentration and distribution of VFAs is the
result of acidogenic metabolic pathways, which can be affected by the micro
environment (e.g. pH) in the digester. Hence, the clear elucidation of the
acidogenic metabolic pathways is essential for optimization of acidogenic process
for efficient product recovery. This review summarizes major acidogenic metabolic
pathways and regulating strategies for enhancing VFAs recovery during acidogenic
fermentation of FW.
PMID- 28693951
TI - Gene silencing of stearoyl-ACP desaturase enhances the stearic acid content in
Chlamydomonas reinhardtii.
AB - In this study, stearoyl-ACP desaturase (SAD), the enzyme that converts stearic
acid into oleic acid, is silenced by artificial microRNA in the green microalga
Chlamydomonas reinhardtii. Two different constructs, which target different
positions on the mRNA of stearoyl-ACP desaturase, were tested. The mRNA levels
for SAD were reduced after the silencing construct was induced. In one of the
strains, the reduction in SAD mRNA resulted in a doubling of the stearic acid
content in triacylglycerol molecules, which shows that stearic acid production in
microalgae is possible.
PMID- 28693952
TI - Pathogenesis of adenomyosis: an update on molecular mechanisms.
AB - Adenomyosis is a uterine disorder becoming more commonly diagnosed in women of
reproductive age because of diagnostic imaging advancements. The new
epidemiological scenario and the clinical evidence of pelvic pain, abnormal
uterine bleeding and infertility are changing the classic perspective of
adenomyosis as a premenopausal disease. In the last decade, the evaluation of
multiple molecular mediators has improved our knowledge of pathogenic mechanisms
of adenomyosis, supporting that this is an independent disease from
endometriosis. Although they share common genetic mutations and epigenetic
changes in sex steroid hormone receptors and similar inflammatory mediators, an
increasing number of recent studies have shown pathogenic pathways specific for
adenomyosis. A PubMed search up to October 2016 summarizes the key mediators of
pain, abnormal uterine bleeding and infertility in adenomyosis, including sex
steroid hormone receptors, inflammatory molecules, extracellular matrix enzymes,
growth factors and neuroangiogenic factors.
PMID- 28693953
TI - Cryopreservation of Luciola praeusta Kiesenwetter (Coleoptera: Lampyridae)
embryos by vitrification.
AB - There is an urgent need to preserve the ever-decreasing number of different
species of fireflies all over the world. We sought to develop a vitrification
procedure to cryopreserve the firefly embryos. The late stages of Luciola
praeusta Kiesenwetter embryos were collected. Several impermeable and permeable
protectants with various concentrations in different mediums (TNM-FH insect
medium, Grace's medium, Dulbecco's Modification of Eagle's Medium (DMEM) and
Dulbecco's Phosphate-Buffered Saline (DPBS)) were used. Embryos culturing in TNM
FH medium yielded the highest survival rate of 75.3 +/- 3.6%. One-step, two-step
and three-step methods were used in equilibrium procedure respectively. The
highest survival rate (73.7% +/-3.2%) occurred in embryos treated by three-step
method ((1.5 M ethylene glycol (EG) + 2 M EG plus 8% polyvinylpyrrolidone (PVP) +
3 M EG, 8% PVP and 15% trehalose). Additionally, embryos exposed to 0.5 M
trehalose presented a significantly higher survival rate (71.8 +/- 2.7%) than
embryos preserved in 0.5 M sucrose.
PMID- 28693954
TI - Nano-encapsulation of chicken immunoglobulin (IgY) in sodium alginate
nanoparticles: In vitro characterization.
AB - Controlled delivery of therapeutic agents by alginate nanoparticles became an
attractive issue in the gastric organ. Some therapeutic agents such as proteins
could not tolerate in severe condition in the gastrointestinal tract. In the
present study, four concentrations of a specific IgY as a prophylactic agent
against E. coli O157: H7 was entrapped in 0.2% w/v sodium alginate nanoparticles
by ionic gelation method. Depending on the IgY concentration entrapment efficacy
was 28.31-99.84%. The physicochemical and structural characteristics of free and
IgY-loaded Alg NPs revealed that the individual particles exhibited a spherical
shape with a diameter of 45-85 nm, and a negatively charged surface with a zeta
potential value of 26-36 mV. In vitro release study showed a high significant
difference of released amounts of IgY at 10% and 99.84% in simulated gastric
fluid (pH 1.2) and simulated intestine fluid (pH 6.8), respectively. Also, the
quality and activity of released IgY from Alg NPs not changed. The cytotoxicity
of different concentrations of Alg NPs on the Vero cells was measured. Our
results indicated that Alg NPs prepared from 0.2%w/v stock solution could be
appropriate candidates for efficient and safe delivery of IgY through the
gastrointestinal tract.
PMID- 28693955
TI - Adaptogenic potential of Oxitard in experimental chronic stress and chronic
unpredictable stress induced dysfunctional homeostasis in rodents.
AB - BACKGROUND: Oxitard, a polyherbal formulation comprising the extracts of Withania
somnifera, Mangifera indica, Glycyrrhiza glabra, Daucus carota, Vitis vinifera,
powders of Syzygium aromaticum, Yashada bhasma and Emblica officinalis; and oils
of Triticum sativum. OBJECTIVE: Current study deals with the assessment of
Oxitard (a marketed polyherbal formulation) for its adaptogenic potential in
chronic unpredictable stress (CUS) and chronic stress (CS) induced dysfunctional
homeostasis in rodents. MATERIALS & METHODS: Animals were immobilized for 2 h
every day for ten days to induce CS. In order to induce CUS, animals were
employed in a battery of stressors of variable value and duration for ten days.
Following administration of Oxitard, stress was induced in the animals. Stress
induced efficient changes were evaluated by assessing organ (adrenal gland)
weights, ulcer index, hematological parameters and biochemical levels of reduced
glutathione (GSH), thiobarbituric acid reactive substances (TBARS) and catalase
(CAT). RESULTS: CS and CUS significantly modified the oxidative stress parameters
(increased MDA and decreased GSH). Furthermore, CS and CUS lead to weight
reduction, adrenal hypertrophy and gastric ulceration. Pre-treatment with Oxitard
(200 and 400 mg/kg, p.o.) significantly modified CS and CUS induced hematological
changes, oxidative stress parameters and pathological effects. CONCLUSION: In
conclusion, Oxitard-intervened antioxidant actions are accountable for its
adaptogenic effects in stress-induced dysfunctional homeostasis.
PMID- 28693956
TI - Mechanistic insights of the enhancement effect of sorbitan monooleate on
olanzapine transdermal patch both in release and percutaneous absorption
processes.
AB - In this paper, based on the optimized formulation of olanzapine (OLN) transdermal
patch, the role of sorbitan monooleate (SP) in OLN release and percutaneous
absorption processes was probed in vitro and in vivo. Rheological test, DSC, FT
IR and molecular modeling were conducted to elucidate the effect of SP on the
release process of OLN from transdermal patch. Additionally, the action of SP on
the percutaneous absorption process was probed using tape stripping transdermal
experiment, confocal laser scanning microscopy (CLSM), ATR-FTIR and molecular
docking. The results showed that the hydrogen bonding interaction between OLN and
pressure sensitive adhesive (PSA) was weakened by SP, which resulted in a
decrease in the cohesive interaction between polymer chains and an increase in
the formation of free volume of PSA, thus, the release of OLN from patch was
promoted. Meanwhile, the OH groups of SP interacted with the polar head groups of
the ceramides, which increased the fluidity of the skin lipids, thereby improved
the ability of OLN percutaneous absorption. In summary, this study demonstrated
that not only the release but also the percutaneous absorption processes were
promoted by SP. This study provided comprehensive molecular level understanding
on the effect of penetration enhancer on transdermal patch and strategies for
rationally selection of chemical enhancer for transdermal drug delivery systems.
PMID- 28693957
TI - Follicle-stimulating hormone encapsulation in the cholesterol-modified chitosan
nanoparticles via molecular dynamics simulations and binding free energy
calculations.
AB - Follicle-stimulating hormone (FSH) is widely applied in the modern ovarian
stimulation techniques. However, it must be administered daily because of its
short half-life. Recently, the cholesterol (CS) modified chitosan (CTS) nanogels
have attracted significant interest as promising controlled release protein
delivery because of their ability to minimize the aggregation and irreversible
denaturation of proteins. Herein, we report a molecular dynamics (MD) simulation
investigation on the molecular mechanisms of FSH encapsulation in the CS-CTS
nanogels. The MD simulations have been performed using the GROMACS software for
up to 200ns simulation time. Furthermore, the binding free energy has been
calculated by the molecular mechanics [MM] with Poisson-Boltzmann [PB] and
surface area solvation (MM/PBSA) method by using the g_mmpbsa tool. Our findings
suggest that the main driving force of the formation of the CS-CTS nanogels is
the hydrophobic interactions between the CS-CS moieties in water. The results
have also indicated that the CS-CTS nanogel formation can occur through the
hydrogen bonding in addition to the hydrophobic interactions. The obtained data
demonstrate that the FSH encapsulation into the CS-CTS nanogels is a gradual
process driven by the hydrophobic interactions between the hydrophobic patch of
FSH and the hydrophobic nanodomains of the nanogel. Our results also reveal that
except in the hydrophobic patch region, the flexibility of FSH was reduced in the
presence of the nanogel. This study provides the elucidation of the nanogel-FSH
interactions at the molecular level and presents new perspective for the ideal
design and applications of the CS-CTS nanogel in protein delivery.
PMID- 28693958
TI - Childhood Obesity, Obesity Treatment Outcome, and Achieved Education: A
Prospective Cohort Study.
AB - PURPOSE: Childhood obesity represents a social burden. This study aims to
investigate whether achieved educational level differs in young adults who have
suffered obesity in childhood compared with the general population and to
determine how obesity treatment influences achieved educational level. METHODS:
This prospective cohort study includes subjects from the Swedish Childhood
Obesity Treatment Registry (BORIS, n = 1,465) who were followed up after 20 years
of age. They were compared with a randomly selected matched population-based
group (n = 6,979). Achieved educational level was defined as >=12 years in school
(completers). Covariates include sex, migration background, and attention deficit
disorders for both groups. Furthermore, age and degree of obesity at start of
obesity treatment, treatment duration, and efficacy were analyzed in the obese
cohort. RESULTS: In the obese cohort, 55.4% were school completers, compared with
76.2% in the comparison group (adjusted odds ratio [OR] = .42, p < .0001).
Subjects with moderate obesity had a completion rate of 64.4%, compared with
50.9% among subjects with morbid obesity (adjusted OR = .57, p < .0001).
Successful obesity treatment was associated with increased future educational
level, compared with those experiencing no treatment effect (61.9% vs. 51.3%
completers; adjusted OR = 1.4, p < .05). In children with attention deficit
disorder, obesity was not an extra risk for not completing 12 or more years of
schooling, p = .11. CONCLUSIONS: Obesity in childhood was associated with low
educational level in early adulthood. Children and adolescents with obesity may
require special support at school in addition to health care treatment to lose
weight.
PMID- 28693959
TI - Value and limits of stapled transanal rectal repair for obstructed defecation
syndrome: 10 years-experience with 450 cases.
AB - BACKGROUND/OBJECTIVE: In the late's 90' a new surgical treatment, the stapled
trans-anal rectal resection (STARR) was born to treat obstructed defecation
syndrome (ODS). In this study we retrospectively analyze a series of 450 cases
that underwent STARR in 10 years. METHODS: Between January 2001 to December 2011,
450 patients, diagnosed with ODS syndrome caused by rectocele or intussusception,
underwent to STARR procedure. The presence of rectocele and/or intussusception
was verified by dynamic defecography. The preoperative evaluation was completed
with anorectal manometry and colonoscopy. Follow-up visits were scheduled 1 week,
1 month, 3 months, 1 years, 3 years and 5 years after surgery. RESULTS: Mean
operative time was 30,2 min. In 408 cases (90.7%) hospital discharge occurred 24
hours after surgery. Among postoperative complications urinary retention was
observed in 35 patients (7.8%). Five (1.1%) patients presented an early rectal
bleeding and 8 (1.8%) patients presented a late bleeding. In 5 (1.1%) patients a
stable pelvic hematoma was found. Six (1.3%) patients presented pelvic sepsis due
to subperitoneal perforation. An asymptomatic partial dehiscence of stapler row
occurred in 19 patients (4.2%).125 patients (27.8%) reported defecation urgency
that completely vanished at 3 months follow-up in 83 patients (66,4%) and in
further 42 patients (33,6%) at 6-months. The average preoperative ODS score was
14.1; 3.1 at one year; 4.3 at 3 years and 6.4 after five years. CONCLUSIONS: In
expert hands, with right indications, STARR procedure is safe with good results
in terms of improvement of the ODS score.
PMID- 28693960
TI - The lateral "backdoor" approach to open thyroid surgery: A comparative study.
AB - INTRODUCTION: The traditionally taught technique for conventional open
thyroidectomy is via a midline splitting of the strap muscles following a skin
crease neck incision - midline approach (MA). The lateral "backdoor" approach
(LA) uses the same central neck incision but approaches the thyroid gland between
the anterior border of sternocleidomastoid (SCM) and strap muscles. This
technique is usually reserved for re-do thyroid surgery. We compared the results
of the two approaches in patients undergoing conventional thyroidectomy for the
first time. METHODS: A case-control study was performed on 90 patients undergoing
conventional open thyroidectomy from 2012 to 2014. The first 45 patients
underwent MA and subsequent 45 patients underwent LA. All patients were given 10
ml of 1% Marcaine infiltration into the neck incision before closure. Basic
demographic data, operative time, incision length, weight of gland, need for
transection of strap muscles and complications were recorded. Revision thyroid
surgery and minimally invasive thyroid operations were excluded. RESULTS: The
demographics, operative timing, gland weight and incisional length showed no
significant difference. Post-operative pain was significantly lower in the LA
group. 5 patients (11%) in MA group needed horizontal transection of strap
muscles to extract large goitres compared to 1 patient (2.2%) in the LA group. No
major complications occurred in either group. CONCLUSION: The LA method is as
safe as the midline technique with comparable operative time and significantly
lower pain scores. It avoids midline separation and suturing of strap muscles and
reduces the need for strap muscle transection to removal large goitres.
PMID- 28693961
TI - Agency and the Calibration of Motivated Behavior.
AB - The controllability of positive or negative environmental events has long been
recognized as a critical factor determining their impact on an organism. In
studies across species, controllable and uncontrollable reinforcement have been
found to yield divergent effects on subsequent behavior. Here we present a model
of the organizing influence of control, or a lack thereof, on the behavioral
repertoire. We propose that individuals derive a generalizable estimate of agency
from controllable and uncontrollable outcomes, which serves to calibrate their
behavioral strategies in a manner that is most likely to be adaptive given their
prior experience.
PMID- 28693962
TI - The impact of triglycerides on glucose tolerance: Lipotoxicity revisited.
AB - Elevated plasma triglycerides (TGs) are early key features of conditions
associated with a dysregulation in glucose metabolism and may predict the
development of type 2 diabetes (T2D) over time. Although the acute ingestion of
lipid, either mixed with or shortly before the meal, is neutral or slightly
beneficial on glucose tolerance, a short-term increase in plasma TGs induced by
either an i.v. lipid infusion or a high-fat diet produces a deterioration of
glucose control. Accordingly, chronic lowering of plasma TGs by fibrates improves
glucose homeostasis and may also prevent T2D. The chronic effects of the
elevation of dietary lipid intake are less clear, particularly in humans, being
the quality of fat probably more important than total fat intake. Although on the
bases of the available experimental and clinical evidence it cannot be easily
disentangled, with respect to elevated non-esterified fatty acids (NEFA) the
relative contribution of elevated TGs to glucose homeostasis disregulation seems
to be greater and also more plausible. In conclusion, although the association
between elevated plasma TGs and impaired glucose tolerance is commonly considered
not causative or merely a consequence of NEFA-mediated lipotoxicity, the
available data suggest that TGs per se may directly contribute to disorders of
glucose metabolism.
PMID- 28693963
TI - Intracraneal complications after raquis surgery.
AB - Intracraneal bleeding is a rare complication after raquis surgery. It is believed
to occur as a drop in the intracraneal pressure after a loss of CSF secondary to
an iatrogenic dural tear. We report a patient who after surgery for lumbar
stenosis presented a subarachnoid haemorrhage, an intraparenchymal haematoma, and
a subdural haematoma. To our knowledge, this is the first report in the
literature with such complications after this type of surgery.
PMID- 28693964
TI - Impact of dietary intake, lifestyle and biochemical factors on metabolic health
in obese adolescents.
AB - BACKGROUND AND AIMS: Obesity devoid of metabolic abnormalities is known as
metabolically healthy obesity (MHO). The aim of the study was to examine
determinants of MHO during adolescence. METHODS AND RESULTS: From among 710 obese
adolescents, 43 girls and 57 boys were classified as metabolically unhealthy
(abdominal obesity and >=2 risk components of metabolic syndrome). MHO (absence
of any cardiometabolic risk factor) was found in 211 girls and 131 boys
(regardless of waist circumference) and in 33 girls and 27 boys (without
abdominal obesity). Laboratory and anthropometric parameters, dietary records and
various lifestyle factors were compared between MHO vs. those unhealthy. The
prevalence of MHO regardless of waist circumference was higher in girls than in
boys (53.1 vs. 41.9%) but comparable when abdominal obesity was excluded (8.3 vs.
8.6%). Anthropometric variables, levels of gamma-glutamyl transferase, total and
low-density lipoprotein cholesterol in both genders, hs-C-reactive protein in
girls and alanine aminotransferase in boys differentiated the two metabolic
phenotypes. Uric acid was related to metabolic health only in the analysis of MHO
without abdominal obesity. Total hours of sleep, bedtime, time of the last daily
meal, regular meal consumption and protein intake in boys and screen time, the
score of disinhibition and diet composition in girls were found to impact
cardiometabolic health. CONCLUSIONS: In obese adolescents, metabolic health was
related to anthropometric and biochemical parameters and only weak associations
were found with most of the lifestyle factors studied. Uric acid concentration
associated with metabolic health when abdominal obesity was excluded.
PMID- 28693965
TI - Maternal pre-gravid cardiometabolic health and infant birthweight: A prospective
pre-conception cohort study.
AB - BACKGROUND AND AIMS: Both low birthweight and high birthweight have been
associated with the development of cardiometabolic disease in adulthood, possibly
reflecting the effect of intrauterine fetal programming. As developmental
programming can begin before conception, pre-gravid factors that predict
birthweight may be relevant in this context. However, little is known about such
factors. Thus, we established a pre-conception cohort to identify maternal pre
gravid cardiometabolic determinants of infant birthweight. METHODS AND RESULTS:
In this prospective observational cohort study, 1484 newly-married women in
Liuyang, China, underwent baseline (pre-gravid) evaluation and then were followed
across a subsequent pregnancy. Pre-gravid cardiometabolic characterization
consisted of clinical (anthropometry, blood pressure) and biochemical evaluation
(total/LDL/HDL cholesterol, triglycerides, glucose) at median 20 weeks before a
singleton pregnancy. Mean birthweight was 3294 +/- 444 g, with 173 neonates large
for-gestational-age (LGA) and 110 small-for-gestational-age (SGA). On multiple
linear regression analysis, positive determinants of birthweight were maternal
age, pre-gravid body mass index (BMI), weight gain in pregnancy, length of
gestation, and male infant (all p <= 0.0003). On logistic regression analysis,
independent predictors of an LGA delivery were maternal age (OR = 1.10 per year,
95%CI 1.03-1.18), pre-gravid BMI (OR = 1.21 per kg/m2, 1.07-1.37), and
gestational weight gain (OR = 1.10 per kg, 1.06-1.14). The only independent
predictor of SGA was gestational weight gain (OR = 0.93 per kg, 0.89-0.97).
CONCLUSION: Maternal weight before and during pregnancy is the predominant
cardiometabolic determinant of infant birthweight, rather than pre-gravid blood
pressure, glucose or lipid profile.
PMID- 28693966
TI - Corrigendum to "Proactive sustainability strategy and corporate sustainability
performance: The mediating effect of sustainability control systems" [J. Environ.
Manag. 196 (2017) 569-582].
PMID- 28693967
TI - Comparison of balance of tritium activity in waste water from nuclear power
plants and at selected monitoring sites in the Vltava River, Elbe River and
Jihlava (Dyje) River catchments in the Czech Republic.
AB - During the routine operation, nuclear power plants discharge waste water
containing a certain amount of radioactivity, whose main component is the
artificial radionuclide tritium. The amounts of tritium released into the
environment are kept within the legal requirements, which minimize the noxious
effects of radioactivity, but the activity concentration is well measurable in
surface water of the recipient. This study compares amount of tritium activity in
waste water from nuclear power plants and the tritium activity detected at
selected relevant sites of surface water quality monitoring. The situation is
assessed in the catchment of the Vltava and Elbe Rivers, affected by the Temelin
Nuclear Power Plant as well as in the Jihlava River catchment (the Danube River
catchment respectively), where the waste water of the Dukovany Nuclear Power
Plant is discharged. The results show a good agreement of the amount of released
tritium stated by the power plant operator and the tritium amount detected in the
surface water and highlighted the importance of a robust independent monitoring
of tritium discharged from a nuclear power plant which could be carried out by
water management authorities. The outputs of independent monitoring allow
validating the values reported by a polluter and expand opportunities of using
tritium as e.g. tracer.
PMID- 28693968
TI - Trichoderma asperellum cultured in reduced concentrations of synthetic medium
retained dye decolourization efficacy.
AB - Trichoderma asperellum (Ta) was first cultured in synthetic medium (Potato
Dextrose Broth, PDB) of various concentrations (100, 75, 50, 25%). The biomass
was harvested and inoculated into dye solutions (crystal violet, CV; methyl
violet, MV; malachite green, MG; and cotton blue, CB). Reduced concentrations
(20, 50, 75%) affected growth rate but their decolourization efficacies remained
unaffected. This was attributed to similar numbers and types of functional groups
(hydroxyl, amine, ester-lipid, alkane groups) found on the surface of fungal
biomass, as revealed by the Fourier transformed infrared spectroscopy (FTIR)
analysis. Their production of NADH-reductase for degradation, and their
biosorption activities were also unaffected. In general, Ta cultured in reduced
concentrations (20, 50, 75%) retained the ability to perform biosorption and
biodegradation, similar to cultures from control (100% PDB). This suggested that
reduced nutrient levels (as a cost-feasible strategy) could be used to cultivate
biomass of Ta for dye removal activities.
PMID- 28693969
TI - The influence of physical activity in water on sleep quality in pregnant women: A
randomised trial.
AB - INTRODUCTION: Sleep is a physiological state of self-regulation. The
international classification of sleep disorders now includes as a new category
those occurring during pregnancy. Regular physical activity is known to improve
the quality of life, one aspect of which is sleep quality. During pregnancy,
physical activity is decreased but should not be eliminated, as studies have
reported a high correlation between sleep disorders and the absence of physical
activity. Regular physical exercise during pregnancy, whether performed in water
or out of it, provides greater control of gestational weight gain. Furthermore,
the reduced weight gain during pregnancy, as a result of physical exercise, is
associated with greater physical resistance to the demands of childbirth, combats
the fatigue caused by pregnancy and reduces back pain. All of these outcomes tend
to enhance sleep quality, among other beneficial effects. OBJECTIVE: To determine
whether, in pregnant women, there is an association between moderate-intensity
physical activity in an aquatic environment and sleep quality. MATERIAL AND
METHODS: A randomised clinical trial was conducted with a sample of 140 pregnant
women aged 21-43 years, divided into two groups; Intervention Group and Control
Group. The women were recruited in the twelfth week of gestation and took part in
the [Study of] Water Exercise in Pregnancy programme from week 20 to week 37.
Sleep quality was evaluated in the first and third trimesters of pregnancy, using
the Pittsburgh Sleep Quality Index questionnaire. RESULTS: The Mann-Whitney U
test showed that the results obtained were statistically significant (p<0.05). In
the Intervention Group, 44 of the women (65.67%) were classified as "poor
sleepers" versus 62 women (92.54%) in the Control Group. CONCLUSIONS: The [Study
of] Water Exercise in Pregnancy method improves the quality of sleep in pregnant
women, both subjectively and in terms of latency, duration and efficiency.
PMID- 28693970
TI - Development of a sedation protocol using orally administered tiletamine-zolazepam
acepromazine in free-roaming dogs.
AB - OBJECTIVE: To investigate the sedative effects in dogs of tiletamine-zolazepam
acepromazine (TZA) or ketamine-flunitrazepam (KF) administered orally and to
evaluate the effectiveness of encapsulated TZA for capturing free-roaming dogs.
STUDY DESIGN: Experimental study followed by a field trial. ANIMALS: Six research
dogs and 27 free-roaming dogs. METHODS: In a pilot study, six research dogs were
administered liquid TZA (20 mg kg-1 tiletamine-zolazepam and 2 mg kg-1
acepromazine) or liquid KF (50 mg kg-1 ketamine and 2 mg kg-1 flunitrazepam)
orally: treatment 1, forcefully squirting liquid medication into the mouth;
treatment 2, encapsulating liquid medication for administration in canned food;
treatment 3, administering liquid medication mixed with gravy. Sedation was
scored. A follow-up field trial attempted capture of 27 free-roaming dogs.
RESULTS: In the pilot study, the median time (range) to lateral recumbency (%
dogs) after TZA administration was: treatment 1, 47.5 (35-80) minutes (67%);
treatment 2, 30 (15-65) minutes (83%); and treatment 3, 75 (45-110) minutes
(100%). No dogs in KF treatment 2 or 3 achieved lateral recumbency. Based on
these results, 20 free-roaming dogs were offered encapsulated TZA in canned food:
TZ (20 mg kg-1) and acepromazine (2 mg kg-1). Of these, no further drugs to four
dogs (one dog captured), 10 dogs were administered a second dose within 30
minutes (five dogs captured) and six dogs were administered TZ (5 mg kg-1) and
xylazine (1.1-2.2 mg kg-1) intramuscularly by blow dart (six dogs captured).
Seven dogs were initially offered twice the TZA dose (five dogs captured). In
total, 63% free-roaming dogs were captured after administration of encapsulated
TZA in canned food. CONCLUSIONS AND CLINICAL RELEVANCE: Oral administration of
encapsulated TZA in canned dog food can aid in the capture of free-roaming dogs,
but additional drugs may be required. The sedation onset time and medication
palatability influenced the capture rate.
PMID- 28693972
TI - Polymer-interaction driven diffusionof eyeshadow in soft contact lenses.
AB - Soft contact lenses used for the correction of ametropia are often made of
hydrogel and silicone-hydrogel materials. Since they are placed directly on the
surface of the eye and they are hydrated by tears, eye cosmetics can compromise
the lens performance and, even worse, can be transported from an external
environment to the ocular surface through the contact lens. The diffusion of the
dye component of a purple eyeshadow in soft contact lenses of different materials
is here evaluated. Diffusivity is found to be typically higher in silicone
hydrogels than in hydrogels. In hydrogels, diffusivity is greater in the case of
lower oxygen transmissibility. Despite differences between materials, absorbed
mass of dye is much larger (10-100 times) than the expected mass by simple
hydration and swelling of the contact lens. The most contaminated materials are
also resistant to cleaning solutions. The results indicate that, notwithstanding
the complexity of contact lens networks, diffusion of dye is found to follow
Fick's law and it is driven by polymer-dye interaction, which governs lens
hydration and swelling.
PMID- 28693971
TI - Gut microbiome, metabolome, and allergic diseases.
AB - The number of patients with allergic and inflammatory disorders has been
increasing during the past several decades. Accumulating evidence has refined our
understanding of the relationship between allergic diseases and the gut
microbiome. In addition, the gut microbiome is now known to produce both useful
and harmful metabolites from dietary materials. These metabolites and bacterial
components help to regulate host immune responses and potentially affect the
development of allergic diseases. Here, we describe recent findings regarding the
immunologic crosstalk between commensal bacteria and dietary components in the
regulation of host immunity and the influence of this relationship on the
development of allergic diseases.
PMID- 28693973
TI - Rationally combining immunotherapies to improve efficacy of immune checkpoint
blockade in solid tumors.
AB - With the widespread application of immune checkpoint blocking antibodies (ICBs)
for the treatment of advanced cancer, immunotherapy has proven to be capable of
yielding unparalleled clinical results. However, despite the initial success of
ICB-treatment, still a minority of patients experience durable responses to ICB
therapy. A plethora of mechanisms underlie ICB resistance ranging from low
immunogenicity, inadequate generation or recruitment of tumor-specific T cells or
local suppression by stromal cells to acquired genetic alterations leading to
immune escape. Increasing the response rates to ICBs requires insight into the
mechanisms underlying resistance and the subsequent design of rational
therapeutic combinations on a per patient basis. In this review, we aim to
establish order into the mechanisms governing primary and secondary ICB
resistance, offer therapeutic options to circumvent different modes of resistance
and plea for a personalized medicine approach to maximize immunotherapeutic
benefit for all cancer patients.
PMID- 28693974
TI - The added value of type I interferons to cytotoxic treatments of cancer.
AB - Type I interferons (IFNs) exert anti-proliferative, antiviral and
immunomodulatory activities. They are also involved in cell differentiation and
anti-tumor defense processes. A growing body of literature indicates that the
success of conventional chemotherapeutics, epigenetic drugs, targeted anticancer
agents and radiotherapy (RT) relies, at least in part, on the induction of type I
IFN signaling in malignant cells, tumor-infiltrating antigen presenting cells or
other immune cells within lymphoid organs or blood. The mechanisms underlying
type I IFN induction and the clinical consequences of these observations are only
beginning to be elucidated. In the present manuscript, we reviewed the recent
advances in the field and provided our personal view on the role of type I IFNs
induced in the context of cytotoxic anticancer treatments and on its possible
exploitation as a complement in cancer therapy.
PMID- 28693975
TI - Reply to the letter to the editor regarding "The diagnostic advantage of EOB-MR
imaging over CT in the detection of liver metastasis in patients with potentially
resectable pancreatic cancer: Methodological issues".
PMID- 28693976
TI - Effectiveness of the Spirometry 360 Quality Improvement Program for Improving
Asthma Care: A Cluster Randomized Trial.
AB - OBJECTIVE: To determine the effectiveness of the Spirometry 360 distance learning
quality improvement (QI) program for enhancing the processes and outcomes of care
for children with asthma. METHODS: Cluster randomized controlled trial involving
25 matched pairs of pediatric primary care practices. Practices were recruited
from 2 practice-based research networks: the Slone Center Office-based Research
Network at Boston University, Boston, Mass, and the Puget Sound Pediatric
Research Network, Seattle, Wash. Study participants included providers from one
of the 50 enrolled pediatric practices and 626 of their patients with asthma.
Process measures assessed included spirometry test quality and appropriate
prescription of asthma controller medications. Outcome measures included asthma
specific health-related quality of life, and outpatient, emergency department,
and inpatient utilization for asthma. RESULTS: At baseline, 25.4% of spirometry
tests performed in control practices and 50.4% of tests performed in intervention
practices were of high quality. During the 6-month postintervention period, 28.7%
of spirometry tests performed in control practices and 49.9% of tests performed
in intervention practices were of high quality. The adjusted difference-of
differences analysis revealed no intervention effect on spirometry test quality.
Adjusted differences-of-differences analysis also revealed no intervention effect
on appropriate use of controller medications or any of the parent- or patient
reported outcomes examined. CONCLUSIONS: In this study, the Spirometry 360
distance learning QI program was ineffective in improving spirometry test quality
or parent- or patient-reported outcomes. QI programs like the one assessed here
may need to focus on practices with lower baseline performance levels or may need
to be tailored for those with higher baseline performance.
PMID- 28693977
TI - Academic Pediatric Association Research Award Acceptance Speech May 2017, San
Francisco, California.
PMID- 28693978
TI - Pyogenic liver abscesses: a contemporary analysis of management strategies at a
tertiary institution.
AB - BACKGROUND: Despite equivocal evidence, non-surgical management for pyogenic
liver abscess (PLA) has become the standard of care at most institutions with
surgery relegated to salvage therapy for those who fail less invasive means. The
aim of this study was to describe the outcomes of a step-up approach to PLA
management. METHODS: A retrospective chart review was conducted at a single
institution for patients diagnosed with PLA over a 10-year period. Demographic,
radiologic, microbiological, treatment, and outcomes data were collected and
analyzed. RESULTS: 64 patients with PLA were identified. Initial treatment
included antibiotics alone (n = 9), percutaneous drainage (PD) (n = 54), and
surgery (n = 1). Surgery was ultimately required in 8 patients while 50 were
cured with PD and 4 with antibiotics alone. Two (3%) patients died. Overall, PD
carried an 85% success rate. CONCLUSION: PLA patients should be initially treated
non-operatively, barring indications for emergent surgery or inaccessibility for
PD. Surgery can be reserved for failure of PD.
PMID- 28693979
TI - The predictive value of C-reactive protein (CRP) in acute pancreatitis - is
interval change in CRP an additional indicator of severity?
AB - BACKGROUND: Using revised Atlanta classification defined outcomes, we compare
absolute values in C-reactive protein (CRP), with interval changes in CRP, for
severity stratification in acute pancreatitis (AP). METHODS: A retrospective
study of all first incidence AP was conducted over a 5-year period. Interval
change in CRP values from admission to day 1, 2 and 3 was compared against the
absolute values. Receiver-operator characteristic (ROC) curve and likelihood
ratios (LRs) were used to compare ability to predict severe and mild disease.
RESULTS: 337 cases of first incidence AP were included in our analysis. ROC curve
analysis demonstrated the second day as the most useful time for repeat CRP
measurement. A CRP interval change >90 mg/dL at 48 h (+LR 2.15, -LR 0.26) was
equivalent to an absolute value of >150 mg/dL within 48 h (+LR 2.32, -LR 0.25).
The optimal cut-off for absolute CRP based on new, more stringent definition of
severity was >190 mg/dL (+LR 2.72, -LR 0.24). CONCLUSION: Interval change in CRP
is a comparable measure to absolute CRP in the prognostication of AP severity.
This study suggests a rise of >90 mg/dL from admission or an absolute value of
>190 mg/dL at 48 h predicts severe disease with the greatest accuracy.
PMID- 28693980
TI - Low-Fat or Low Carb for Weight Loss? It Depends on Your Glucose Metabolism.
PMID- 28693981
TI - A Case-control Study Adds a New Piece to the Aluminium/Breast Cancer Puzzle.
PMID- 28693982
TI - Assessing and Promoting the Wellness of United States Ophthalmology Residents: A
Survey of Program Directors.
AB - OBJECTIVE: To report on the status of residency-based wellness initiatives in
ophthalmic graduate medical education and identify strategies for promoting
ophthalmology resident wellness by surveying US ophthalmology program directors
(PDs). DESIGN: The PDs were each sent an e-mail containing a link to an anonymous
online 15-question survey. The PDs also received a letter with the survey link
and a $1 incentive. After 2 weeks, nonresponders received 2 weekly reminder e
mails and phone calls. Descriptive statistics were used to analyze the multiple
choice responses and categorize the free response answers. SETTING: National
survey. PARTICIPANTS: All 111 US ophthalmology PDs were invited to participate.
RESULTS: Of 111 PDs, 56 (50%) responded; 14 (26%) of 53 respondents reported that
their programs faced an issue involving resident depression, burnout, or suicide
within the last year; 25 (45%) of 56 reported that their department had a
resident wellness program. Respondents without wellness programs reported a
shortage of time (19/30; 63%) and lack of training and resources (19/30; 63%) as
barriers to instituting these programs. Respondents reported that the
Accreditation Council for Graduate Medical Education could better promote
resident wellness by providing training resources for burnout and depression
screening (35/53; 66%), resilience skills building (38/53; 72%), and wellness
program development (36/53; 68%). CONCLUSIONS: This survey suggests that there is
a substantial burden of burnout and depression among residents in ophthalmic
graduate medical education and that this burden can be addressed by promoting the
training of educators to recognize the signs of burnout and depression, and
providing resources to develop and expand formal wellness programs.
PMID- 28693983
TI - A prospective randomized study comparing centrifugation and sedimentation for fat
grafting in breast reconstruction.
AB - BACKGROUND: Fat grafting is an efficient method to correct large volumetric
defects after mastectomy. There is an ongoing debate regarding the best method of
processing the harvested fat before fat grafting. This study aimed to introduce a
new MRI model and to compare two fat processing techniques measuring the gain in
soft tissue thickness after fat grafting to the chest wall. METHODS: Fifty-one
mastectomy patients (one double sided), who required delayed implant
reconstruction, with poor skin conditions were proposed fat grafting prior to
implant reconstruction. At the time of fat grafting, patients were randomly
assigned to centrifugation or sedimentation of the aspirated fat. The trial was
undertaken in a single-center private practice setting. The gain in soft tissue
thickness of the chest wall was measured using an MRI model, with 12 predefined
points for measurement. Two MRIs were performed, one prior to fat grafting and
one 8 weeks thereafter. The radiologist was blinded to the fat graft processing
method used. RESULTS: Seven cases were excluded because they did not complete
their second MRI. The analyses were thus based on 44 patients (one double sided).
Centrifugation was performed in 21 cases and sedimentation in 24 cases. The mean
gain in soft tissue thickness was +7.0 mm in the centrifugation group and +8.8 mm
in the sedimentation group (p = .268). The mean operative time was 88 min in the
centrifugation group and 78 min in the sedimentation group (p = .11). There were
no adverse events for any of the patients. CONCLUSIONS: We developed a simple and
reproducible MRI model to objectively measure and evaluate different fat
processing techniques prior to fat grafting. At a median time of 8 weeks after
one session of fat grafting, there was no benefit of centrifugation over
sedimentation.
PMID- 28693984
TI - What factors influence weight loss in participants of commercial weight loss
programmes? Implications for health policy.
AB - BACKGROUND: Finding effective referral policies for weight management services
would have important public health implications. AIM: Here we compare percentage
weight change by referral methods, BMI categories and participants who have had
attended weight loss programmes multiple times. DESIGN AND SETTINGS: A
prospective cohort study of 15,621 participants referred to 12-week behavioural
weight loss programmes funded by the public health service in Birmingham, UK.
METHODS: Comparisons were made between GP versus self-referrals, BMI >=40kg/m2
<40kg/m2 and multiple referrals compared to only one referral. Linear mixed
modelling was used to assess percentage weight change after adjusting for
covariates. RESULTS: Participant's mean age was 48.5 years, 78.7% were of white
ethnicity, 90.3% female and mean baseline BMI was 36.3kg/m2. There were no
significant differences in percentage weight loss, between participants that self
referred and those that were referred by their general practitioner (GP) and no
significant differences between baseline BMI categories. Referral to a weight
loss programme more than once was associated with less weight loss at subsequent
attendances (0.92%, 95% CI 0.70-1.14, p<0.001). CONCLUSION: Allowing self
referral to a weight loss programme widens access without compromising amount of
weight lost. These programmes are beneficial for all categories of obesity,
including those with a BMI >=40kg/m2. Attending weight management programmes more
than once results in less weight loss and that swapping to a different program
may be advisable.
PMID- 28693985
TI - Cardiovascular risk markers among obese women using the levonorgestrel-releasing
intrauterine system: A randomised controlled trial.
AB - According to international guidelines, women with obesity without other
comorbidities can safely use any hormonal contraceptive (HC). However, limited
information is available about contraceptive safety for women with obesity since
obesity is an exclusion criterion of most contraceptive clinical trials. As such
little is known about the possible risks of HC exposure for women with obesity
without comorbidities. One way to assess possible long-term risks in this
population, even prior to the development of any clinical disease, is to measure
alterations in subclinical atherosclerosis markers. We evaluated the effects of
the levonorgestrel-releasing intrauterine system (LNG-IUS) on subclinical markers
of cardiovascular risk in women with obesity. This is a randomised clinical trial
in which 106 women with obesity [body mass index (BMI)>=30kg/m2] were randomised
to the LNG-IUS (n=53) or to non-hormonal methods (n=53) and followed for 12
months. We evaluated waist circumference (WC), blood pressure, blood glucose,
insulin, lipid profile, and endothelial function markers (carotid intima-media
thickness, brachial artery flow-mediated dilation, and carotid arterial
stiffness). At 12 months, BMI (p=0.005), WC (p=0.045), and glucose levels
(p=0.015) were significantly lower in the LNG-IUS group than in the control
group. We did not find any clinically relevant changes in subclinical markers of
cardiovascular risk among with obesity women at 12 months after LNG-IUS placement
compared to users of non-hormonal contraceptive methods.
PMID- 28693986
TI - Do we perform better when we increase red blood cells?
PMID- 28693987
TI - A pragmatic approach to simplify inhaler therapy for COPD.
PMID- 28693989
TI - Osmotic regulation of the mitochondrial permeability transition pore investigated
by light scattering, fluorescence and electron microscopy techniques.
AB - Mitochondrial permeability transition (PT) is a phenomenon of an increase of the
inner membrane permeability in response to an excessive matrix calcium
accumulation. PTP is caused by the opening of the large weakly selective channel.
Molecular composition and regulation of permeability transition pore (PTP) are
not well understood. Here we used isolated mitochondria to investigate dependence
of PTP activation on the osmotic pressure. We found that in low osmotic strength
solution calcium-induced PTP is significantly inhibited. We propose that this
effect is linked to the changes in the curvature of the mitochondrial inner
membrane. This interpretation is consistent with the idea about the importance of
ATP synthase dimerization in modulation of the PTP activity.
PMID- 28693988
TI - Milder clinical and biochemical phenotypes associated with the c.482G>A
(p.Arg161Gln) pathogenic variant in cobalamin C disease: Implications for
management and screening.
AB - INTRODUCTION: Cobalamin C disease is a multisystemic disease with variable
manifestations and age of onset. Genotype-phenotype correlations are well
recognized in this disorder. Here, we present a large cohort of individuals with
cobalamin C disease, several of whom are heterozygous for the c.482G>A pathogenic
variant (p.Arg161Gln). We compared clinical characteristics of individuals with
this pathogenic variant to those who do not have this variant. To our knowledge,
this study represents the largest single cohort of individuals with the c.482G>A
(p.Arg161Gln) pathogenic variant. METHODS: A retrospective chart review of 27
individuals from 21 families with cobalamin C disease who are followed at our
facility was conducted. RESULTS: 13 individuals (48%) are compound heterozygous
with the c.482G>A (p.Arg161Gln) on one allele and a second pathogenic variant on
the other allele. Individuals with the c.482G>A (p.Arg161Gln) pathogenic variant
had later onset of symptoms and easier metabolic control. Moreover, they had
milder biochemical abnormalities at presentation which likely contributed to the
observation that 4 individuals (31%) in this group were missed by newborn
screening. CONCLUSION: The c.482G>A (p.Arg161Gln) pathogenic variant is
associated with milder disease. These individuals may not receive a timely
diagnosis as they may not be identified on newborn screening or because of
unrecognized, late onset symptoms. Despite the milder presentation, significant
complications can occur, especially if treatment is delayed.
PMID- 28693990
TI - Rapid preparation of adherent mammalian cells for basic scanning electron
microscopy (SEM) analysis.
AB - Sample preparation for scanning electron microscope analysis involves reagents
and equipment that are expensive and often hazardous. Here we demonstrate a
circumvention of Osmium tetroxide and critical point drying, greatly reducing the
duration, complexity and cost of the process. We captured early stage
interactions of invasive-bacteria and HeLa cells during the process of bacteria
mediated gene delivery and illustrate sufficient clarity can be obtained using
this procedure to preserve and clearly visualize relevant cellular structures.
This protocol is significantly cheaper and easier to adapt compared to
conventional methods, and will allow routine preparation/viewing of eukaryotic or
bacterial samples for basic morphological studies.
PMID- 28693991
TI - A colorimetric sensor of cysteine based on self-assembly nanostructures of Fe3+
H2O2/Tetramethylbenzidine system with "On-Off" switching function.
AB - Many strategies have been explored for selectively and sensitively detecting
cysteine in different samples. Here, a novel colorimetric sensor based on self
assembly nanostructures of Fe3+-H2O2/Tetramethylbenzidine system with dual-level
logic gate function and colorimetric determination of cysteine were firstly
explored. The proposed Fe3+-H2O2-TMB system provides a sensitive optical signal
due to the selectively reductive ability of cysteine to the oxidized TMB and thus
could be successfully applied to the construction of instant on-site visual
detection method with a paper based test strip for cysteine determination in a
sample solution as well as for a dual-level logic gate fabrication.
PMID- 28693992
TI - Characterization of a recombinant xylose tolerant beta-xylosidase from Humicola
grisea var. thermoidea and its use in sugarcane bagasse hydrolysis.
AB - One full-length beta-xylosidase gene (hxylA) was identified from the Humicola
grisea var. thermoidea genome and the cDNA was successfully expressed by Pichia
pastoris SMD1168. An optimization of enzyme production was carried out, and
methanol was found to be the most important parameter. The purified enzyme was
characterized and showed the optimal conditions for the highest activity at pH
7.0 and 50 degrees C, being thermostable by maintaining 41% of its activity after
12h incubated at 50 degrees C. HXYLA is a bifunctional enzyme; it showed both
beta-xylosidase and alpha-arabinfuranosidase activities. The Km and Vmax values
were 1.3mM and 39.1U/mg, respectively, against 4-nitrophenyl beta-xylopyranoside.
HXYLA showed a relatively strong tolerance to xylose with high Ki value of 603mM,
with the xylose being a non-competitive inhibitor. HXYLA was successfully used
simultaneously and sequentially with an endo-xylanase for analysis of synergism
in the degradation of commercial xylans. Furthermore, commercial cellulases
supplementation with HXYLA during sugarcane bagasse hydrolysis increased
hydrolysis in 29%. HXYLA is distinguished from other beta-xylosidases by the
attractive characteristics for industrial applications such as thermostability,
high tolerance xylose and saccharification of biomass by convert xylan into
fementable monosaccharides and improve cellulose hydrolysis.
PMID- 28693993
TI - Probing the interaction of cephalosporin antibiotic-ceftazidime with human serum
albumin: A biophysical investigation.
AB - The fate of drug administered to a living organism depends on drug's
pharmacokinetics as well as pharmacological behavior. Serum albumins (proteins in
blood plasma of human) act as a carrier molecule to deliver the drug at specific
site. In the present study, we have explored the mechanism of interaction between
cephalosporin antibiotic-ceftazidime (CFD) and human serum albumin (HSA) by
spectroscopic and molecular docking studies. Quenching of HSA fluorescence by CFD
inferred that it binds to HSA through static quenching mechanism; with binding
affinity in order of 104M-1. Fluorescence resonance energy transfer (FRET)
results shows that donor and acceptor molecule are at 2.08nm apart and also
reflects the high probability of energy transfer between HSA and CFD. Change in
secondary structure as well as microenvironment around both tryptophan and
tyrosine residue, were monitored by Circular Dichroism (CD) and Synchronous
fluorescence spectroscopy respectively; confirms that CFD increases the alpha
helical secondary structure as well as altered the environment around tryptophan
and tyrosine. The specific binding site of CFD on HSA was determined by site
specific markers and molecular docking methods. CFD preferably bind to subdomain
IIIA (Sudlow site II) on HSA.
PMID- 28693994
TI - Ferritin glycosylated by chitosan as a novel EGCG nano-carrier: Structure,
stability, and absorption analysis.
AB - Ferritin is a shell-like carrier protein with an 8nm diameter cavity which endows
a natural space to encapsulate food and drug components. In this work,
phytoferritin was unprecedentedly glycosylated by chitosan to fabricate ferritin
chitosan Maillard reaction products (FCMPs) (grafting degree of 26.17%, 24h, 55
degrees C). Results indicated that the amide I and II bands of ferritin were
altered due to the chitosan grafting, whereas the ferritin spherical structure
were retained. Simulated digestion analysis showed that the FCMPs were more
resistant to pepsin and trypsin digestion as compared with ferritin alone.
Furthermore, FCMPs were employed as carrier to encapsulate epigallocatechin
gallate (EGCG) molecules with an encapsulation ratio of 12.87% (w/w), and the
resulting FCMPs-EGCG complexes showed a slow release of EGCG in simulated
gastrointestinal tract. Interestingly, different types of food components
displayed different effects in EGCG release behavior from the FCMPs, wherein
proanthocyanidin, milk and soy protein inhibited the EGCG release. In addition,
the absorption of EGCG encapsulated in FCMPs in Caco-2 monolayer model was
significantly improved as compared with free EGCG. This work provides a novel
nano-vehicle for fabricating core-shell systems in food and drug delivery domain.
PMID- 28693995
TI - Application of whey protein-pectin nano-complex carriers for loading of
lactoferrin.
AB - Our aim was to entrap lactoferrin (LF) in complex nano-particles of whey protein
isolate (WPI)-high methoxyl pectin (HMP) with the ratios of 2:1, 1:1, and 1:2
through acidification at pH values of 3, 3.5, and 4. The zeta-potential, size,
sedimentable-complex yield, LF content, encapsulation efficiency, SEM, AFM, FTIR,
and DSC of nano-particles were investigated. Our results revealed that almost all
analyzed parameters of the final nano-particles were related to preparation pH
value, WPI/HMP ratios, and acidification methods In both methods of pre- and post
acidification, the zeta potential was decreased via decreasing of pH from 4 to 3
and particle size was increased at higher HMP ratios to WPI. In general, the pre
blending acidification provided a larger mass of complexes compared with post
blending counterparts. Also, the nano-particles produced by WPI/HMP with the
ratio of 2:1 at pH=3.5 had the smallest sizes. The highest LF content of the
complexes as well as the optimal entrapment efficiency was observed at pH=3.5, in
both methods of post and pre-blending. Finally, the pre-blending by a ratio of
2:1 for WPI/HMP was chosen as the optimal treatment for producing nano-particles
containing LF. This was confirmed by SEM, AFM, FTIR, and DSC studies.
PMID- 28693996
TI - Human epidermal growth factor coupled to different structural classes of cell
penetrating peptides: A comparative study.
AB - Human epidermal growth factor (hEGF) plays important roles in wound healing. Due
to large molecular weight and hydrophilic nature, cellular uptake and skin
permeation of hEGF are very poor, significantly limiting its efficacy. By using
recombinant technology, four structural classes of cell penetrating peptides
(CPPs) were fused at the C-terminus of hEGF, expressed and purified into
homogeneity. Comparative studies were conducted to evaluate their activity,
cytotoxicity, cellular uptake and skin permeation. Cell viability assay and in
vitro scratch wound-healing assay showed that all four fusion proteins had
similar activities with commercial rhEGF. Obvious cytotoxicity was not detected
for EGF-TAT, EGF-Pep-1 and EGF-AA3H. However, EGF-MAP was cytotoxic at both
moderate and high concentrations. Confocal microscopy indicated that the cellular
uptake of the fusion proteins was markedly improved compared with rhEGF, with EGF
TAT and EGF-Pep-1 showing the most abundant presence within cells at incubation
concentration of 25MUM. Permeation across the excised mouse skin followed the
order of EGF-Pep-1>EGF-TAT>EGF-AA3H>rhEGF. These findings demonstrated that there
were great gaps between the abilities of different structural types of CPPs to
deliver EGF across cell membrane and the skin. EGF coupled with a well-chosen CPP
will become a more promising pharmaceutical agent than rhEGF.
PMID- 28693997
TI - Lectin from Canavalia villosa seeds: A glucose/mannose-specific protein and a new
tool for inflammation studies.
AB - With important carbohydrate binding properties, lectins are proteins able to
decipher the glycocode, and as such, they can be used in bioassays involving cell
cell communication, protein targeting, inflammation, and hypernociception, among
others. In this study, a new glucose/mannose-specific lectin from Canavalia
villosa seeds (Cvill) was isolated by a single affinity chromatography step in a
Sephadex(r) G-50 column, with a purification yield of 19.35mg of lectin per gram
of powdered seed. Analysis of intact protein by mass spectrometry showed the
lectin is composed of three polypeptide chains, including a 25.6kDa alpha chain,
12.9KDa beta, and 12.6 KDa gamma fragments, similar to the profile of ConA-like
glucose/mannose-specific lectins. Partial sequence of the protein was obtained by
MS-MALDI TOF/TOF covering 41.7% of its primary structure. Cvill presented sugar
specificity to d-glucose, alpha-methyl-d-mannoside, d-mannose, and glycoproteins
fetuin and ovoalbumin. The lectin characterization showed that Cvill presents
high stability within a broad range of pH and temperature, also showing average
toxicity against Artemia nauplii. The proinflammatory effect of Cvill was
observed by induction of paw edema and hypernociception in mice, with the
participation of the carbohydrate binding site, showing its potential to be used
as tool in inflammation studies.
PMID- 28693998
TI - Long-term treatment adherence to the proprotein convertase subtilisin/kexin type
9 inhibitor alirocumab in 6 ODYSSEY Phase III clinical studies with treatment
duration of 1 to 2 years.
AB - BACKGROUND: Nonadherence to cardiovascular medications, including daily, oral
statin therapy, negatively impacts outcomes in patients requiring low-density
lipoprotein cholesterol (LDL-C)-lowering therapy. The proprotein convertase
subtilisin/kexin type 9 inhibitor alirocumab also reduces LDL-C, but has a
different mode of administration (subcutaneous injection). OBJECTIVE: The
objective of the study was to assess long-term adherence to alirocumab 75 or 150
mg, given every 2 weeks, in phase III trials of patients with sub-optimally
controlled hypercholesterolemia. METHODS: Data were pooled from 6 ODYSSEY trials
(n = 4212) with double-blind treatment durations of 52 to 104 weeks. Adherence
was reported as percentage of days receiving injections according to dosing
schedule and categorized into 100% adherence, below-planned dosing, above-planned
dosing, and both below- and above-planned dosing. Overall adherence was
calculated as 100 - (percentage of days with below-planned dosing + percentage of
days with above-planned dosing). Safety of alirocumab and effect on LDL-C levels
were also evaluated. RESULTS: Adherence was analyzed for 4197 patients (n = 2786
alirocumab; n = 1411 control). Mean overall adherence was high (alirocumab 98.0%;
control 97.8%). Among patients receiving alirocumab, 45.7% were 100% adherent,
20.4% had below-planned dosing, 2.9% had above-planned dosing, and 31.1% had both
below- and above-planned dosing. Mean percentage reduction in LDL-C (baseline to
Week 52) was 45.8% to 61.9%, depending on alirocumab dose, and was comparable
across adherence categories. Treatment-emergent adverse events leading to
alirocumab discontinuation were infrequent and included myalgia and injection
site reactions (<1% each). CONCLUSIONS: Alirocumab injections were associated
with a high level of adherence over >=1 year. Infrequent below- or above-planned
dosing had minimal impact on LDL-C reductions.
PMID- 28693999
TI - [Profunda artery perforator flap: Reliable secondary option for breast
reconstruction?]
AB - BACKGROUND: In recent years, the DIEP-flap has become the standard for autologous
breast reconstruction. However, when abdominal donor site is unavailable,
secondary options are numerous. This report documents our experience with PAP
flap breast reconstruction. METHOD: We carried out a retrospective study of
patients who underwent reconstructive breast surgery by PAP-flaps in our
institution since 2014. RESULTS: Seventeen PAP-flaps were carried out in 15
patients, two of which received consecutive reconstruction of each breast at
distinct intervals. Indication was lack of abdominal excess in 8 patients and
history of abdominoplasty in 6 patients. These six patients and one more had bad
or absence of perforator for DIEP flap. There were 2 flap losses (11.8%). Other
complications included minor dehiscences from seroma at donor site in 6 cases
(35.3%), flap dehiscence in one case (5.8%), and receiver site hematoma in 1
patient (5.8%). DISCUSSION: The authors analyze their series when the high rate
of complications and the results obtained compared to the second alternative
choices of other teams. CONCLUSION: The author is of the opinion that the PAP
Flap is a reliable option as a second choice for breast reconstruction in
patients whose DIEP can not be retained. It is limited in terms of volume and a
third choice should be considered when the indication is to reconstruct a breast
of large volume.
PMID- 28694000
TI - Boceprevir-based triple therapy to rescue HCV genotype 1/HBV dually infected
patients refractory to peginterferon plus ribavirin combination therapy in
Taiwan.
AB - BACKGROUND/PURPOSE: The role of directly-acting antivirals (DAA)-containing
regimens in the treatment of patients dually-infected with hepatitis C virus
(HCV) and hepatitis B virus (HBV) remains unclear. The pilot study aimed to
explore the safety and efficacy of a protease inhibitor, boceprevir, in
combination with peginterferon/ribavirin for HCV genotype 1 (HCV-1)/HBV dually
infected patients refractory to prior peginterferon/ribavirin. METHODS: Twelve
peginterferon-experienced patients dually-infected with HCV-1/HBV were assigned
to receive boceprevir 800 mg, twice a day, plus peginterferon-alpha 2b 1.5
MUg/kg/week and ribavirin 800-1400 mg/day for 36 or 48 weeks. The primary
endpoint was HCV sustained virological response (SVR, HCV RNA undetectable 24
weeks after end-of-treatment). RESULTS: Five patients terminated treatment early
due to adverse events (one at week 4, one at week 46), virological failures (one
non-response and one breakthrough), and patient request (n = 1). Eight patients
achieved HCV SVR (66.7% in full-analysis set and 72.7% in modified intention-to
treat population). The HCV SVR rate was 71.4% (5/7) in prior relapsers, 60.0%
(3/5) in prior null responder; 75% in non-cirrhotic and 50% in cirrhotic
patients. All four patients of prior non-cirrhotic relapsers received 36-week
regimen and achieved HCV SVR. There was no HBV-related hepatic flare. All
patients experienced at least one adverse event. Two had serious adverse events.
CONCLUSION: Boceprevir plus peginterferon/ribavirin is effective in the treatment
of HCV-1/HBV dually infected patients' refractory to prior
peginterferon/ribavirin combination therapy.
PMID- 28694001
TI - Safety and effectiveness of argatroban versus heparin for preventing venous
thromboembolism after lumbar decompressive surgery.
AB - BACKGROUND: To evaluate the safety and effectiveness of argatroban for the
prevention of venous thromboembolism (VTE) after posterior lumbar decompressive
surgery. METHODS: Included in this retrospective study were 556 patients who
underwent posterior lumbar decompressive surgery for trauma and degenerative
diseases. They were divided into two groups: argatroban group (n = 274), and low
molecular weight heparin (LMWH) group (n = 282). The occurrence of postoperative
venous thrombosis and complications including hemorrhage and allergic reaction
was compared between the two groups. Neurological and clinical outcomes in terms
of Visual Analogue Scale (VAS) and the Oswestry Disability Index (ODI) were
assessed before operation and at 6 and 12 months after operation. RESULTS:
Postoperative venous thromboembolism (VTE) occurred in seven patient. No
pulmonary embolism (PE) occurred in any patient. Thrombosis occurred in 3 cases
(1.0%) and bleeding in 1 case (0.04%) in argatroban group vs. 4 (1.4%) and 4
(1.4%) in LMWH group, showing no significant between the two groups (P > 0.05).
There was significant reduction in the severity of back and leg pain (VAS P <
0.05) and significant improvement in the patient quality of life (ODI, P < 0.05)
6 months and 1 year after operation, showing no significant difference between
the two groups (P > 0.05). CONCLUSIONS: Argatroban proved to be equally effective
as LWMH for anticoagulation therapy. Both drugs exhibited a similar preventive
effect against postoperative VTE after posterior lumbar spine surgery, without
increasing the risk of postoperative bleeding. The neurological and clinical
outcomes are satisfactory and similar between the two pharmacological methods.
PMID- 28694002
TI - Failure to rescue in living donor liver transplantation: Patterns and predictors.
AB - BACKGROUND: As a quality assessment tool, failure to rescue (FTR) has been
employed in various surgical specialties. However, its role in liver
transplantation has only recently been explored. To the best of our knowledge,
role of FTR in living donor liver transplant (LDLT) has not been assessed
previously. The objective of the current study was to determine failure to rescue
(FTR) rate and it's predictors in an LDLT center. MATERIALS AND METHODS: We
reviewed a prospectively maintained database of patients who underwent LDLT at
our center between 2012 and 2016. Patients who experienced grade 3B or above
complications on Clavien-Dindo grading were included in this study. Primary
outcome of interest was FTR rate in these patients. FTR was defined as a
preventable major complication followed by death within one year after
transplantation. We also looked at independent predictors of FTR in our patients
and a multivariate analysis was performed. RESULTS: Median age was 48.4(18-73)
years. Male to female ratio was 3.3:1. Median MELD score was 17(6-42). The FTR
rate in the current study was 52/131 (39.6%). Infectious complications were more
common in the FTR group i.e. 22/32(68.8%) versus 10/32 (31.2%) (P < 0.0001).
Biliary complications were more common in the non-FTR group i.e. 49/62 (79.1%)
versus 13/62 (20.9%) (P < 0.0001). On multivariate analysis, there was a 60%
increase in mortality following a major complication in the presence of early
allograft dysfunction (Hazard ratio: 1.6, Confidence interval; 1.2-2.2, P =
0.002). A 40% reduction in FTR was seen in patients with a biliary complication
versus other complications (Hazard ratio: 0.6, Confidence interval = 0.4-0.8, P =
0.009). CONCLUSION: Early allograft dysfunction and biliary complications are
independent predictors of FTR in LDLT.
PMID- 28694003
TI - PD-L1 and immune escape: insights from melanoma and other lineage-unrelated
malignancies.
AB - One of the major breakthroughs in oncology in the past decade has been the
research and development of immune checkpoint inhibitors. Since the discovery of
the PD-1/PD-L1 axis as a key mediator in peripheral self-tolerance and the
subsequent discovery of its role promoting immune escape in cancers, the PD-1/PD
L1 pathway has produced considerable excitement from both a scientific and
therapeutic standpoint. The past decade has seen an explosion in the number of
clinical trials utilizing anti-PD-1/PD-L1 therapy. Notably, pathologists have
played a critical role in the development of these trials, and in guiding the use
of anti-PD-1/PD-L1 therapies in FDA-approved clinical settings. Analysis of
tissue biopsies has been increasingly used to predict patients with which cancers
are most likely to benefit from these new therapies. However, many open questions
remain in a rapidly changing therapeutic and scientific landscape. In this
review, we describe the basic functioning of the PD-1/PD-L1 axis in normal
biology, how it is coopted by cancers to promote immune escape, and then review
the literature regarding the prognostic value of tumoral PD-L1 expression on its
own before discussing recent therapeutic advances, and the emerging role for
pathologists in predicting response to anti-PD-1/PD-L1 therapies. Special
attention is given to melanoma and non-small cell lung cancer, malignancies that
have seen the broadest applications of anti-PD-L1/PD-1 therapies.
PMID- 28694004
TI - Late incidental diagnosis of intrapericardial teratoma - A case report.
AB - We report a case of intrapericardial teratoma, which is a rare primary cardiac
tumor usually found in newborns and infants. Cardiac teratomas can cause
respiratory failure, large accumulations of pericardial fluid and cardiac
compression leading to death in the intrauterine or neonatal period. The case
described is rare because it is of a 16-year-old asymptomatic girl with an
intrapericardial tumor as an incidental echocardiographic finding. Cardiac
magnetic resonance imaging showed a complex pericardial cyst. Due to the
potential for malignant evolution, she was referred for surgery to remove the
tumor and a diagnosis of teratoma was confirmed by histopathology. Clinical
follow-up had a good outcome.
PMID- 28694005
TI - Quantum counting: Operator methods for discrete population dynamics with
applications to cell division.
AB - The set of natural numbers may be identified with the spectrum of eigenvalues of
an operator (quantum counting), and the dynamical equations of populations of
discrete, countable items may be formulated using operator methods. These
equations take the form of time dependent operator equations, involving
Hamiltonian operators, from which the statistical time dependence of population
numbers may be determined. The quantum operator method is illustrated by a novel
approach to cell population dynamics. This involves Hamiltonians that mimic the
process of stimulated cell division. We evaluate two different models, one in
which the stimuli are expended in the division process and one in which the
stimuli act as true catalysts. While the former model exhibits only bounded cell
population variations, the latter exhibits two distinct regimes; one has bounded
population fluctuations about a mean level and in the other, the population can
undergo growth to levels that are orders of magnitude above threshold levels,
through an instability that could be interpreted as a cancerous growth phase.
PMID- 28694006
TI - Neurotoxicity with persistent unilateral ophthalmoplegia from envenoming by a
wild inland taipan (Oxyuranus microlepidotus, Elapidae) in remote outback South
Australia.
AB - INTRODUCTION: A case of life threatening envenoming by a wild specimen of the
inland taipan, Oxyuranus microlepidotus, is described. There have been 11
previously well-documented envenomings by O. microlepidotus, but only 2 were
inflicted by wild snakes. Envenomed patients have presented predominantly with
defibrinating coagulopathy and neurotoxicity. CASE REPORT: The victim was seeking
to observe members of an isolated population of this species and was envenomed
while attempting to photograph an approximately 1.5 m specimen. He reported
feeling "drowsiness" and blurred vision that progressed to ptosis; he later
developed dysphagia and dysarthria. The patient was treated with 1 vial of
polyvalent antivenom, which was later followed with an additional two vials of
taipan monovalent. He was intubated during retrieval, and recovered after 3 days
of intensive care. He had a right ophthalmoplegia that persisted for
approximately 1 week post-envenoming. Despite a positive 20-min whole blood
clotting test, defibrination coagulopathy was absent, and there was no
myotoxicity, or acute kidney injury. DISCUSSION: Physicians presented with a
patient envenomed by O. microlepidotus should remain cognizant of the possible
variability of medically important venom toxins in some populations of this
species. Some patients seriously envenomed by this species may develop persistent
cranial nerve palsies. When clinically indicated, prompt provision of adequate
antivenom is the cornerstone of managing O. microlepidotus envenoming. Rapid
application of pressure-bandage immobilization and efficient retrieval of victims
envenomed in remote locales, preferably by medically well-equipped aircraft,
probably improves the likelihood of a positive outcome.
PMID- 28694007
TI - [Pseudoachondroplasia: Descriptions of a de novo and familial case].
PMID- 28694008
TI - [Reduced-intensity conditioning haematopoietic stem cell transplantation in
genetic diseases: Experience of the Spanish Working Group for Bone Marrow
Transplantation in Children].
AB - INTRODUCTION: Haematopoietic stem cell transplantation (HSCT) involves implanting
cellular elements capable of generating a new and healthy haematopoietic system.
Reduced intensity conditioning (RIC) consists of an immunosuppressive treatment
to facilitate a progressive implant with lower morbidity. This type of
conditioning can also lead to myelosuppression, which is potentially reversible
over time. Reduced intensity conditioning enables HSCT to be performed on
patients with genetic diseases for whom added comorbidity is undesirable due to
the high doses of chemotherapy that accompanies conventional myeloablative
regimens. PATIENTS AND METHODS: An analysis was performed on the outcomes of 68
paediatric patients with genetic diseases who underwent HSCT with RIC between
2005 and 2013 in the of Paediatric Haematopoietic Stem Cell Transplantation Units
that are part of the Spanish Working Group for Bone Marrow Transplantation in
Children. A multicentre study was conducted including 68 patients, of whom 43 had
Primary Immunodeficiency, 21 with congenital haematological diseases, and 4 with
metabolic diseases. RESULTS: Fifty (73.5%) of the 68 patients were still alive.
The Overall Survival (OS) at nine years was 0.74. Twenty-three (33.8%) had some
event during the course of the HSCT, with an event-free survival rate of 0.66.
The OS in patients with haematological diseases was 0.81, being 0.7 in primary
immunodeficiencies, and 0.4 in metabolic diseases. No significant difference was
observed between the 3 groups of diseases. As regards the source of
haematopoietic progenitors, there was an OS rate of 0.74 in patients transplanted
with peripheral blood, 0.70 with bone marrow, and 0.70 and with cord blood, with
no statistically significant differences. CONCLUSIONS: Favourable results have
been obtained in HSCT with reduced intensity conditioning in genetic diseases. It
should be noted that the risks and benefits of the RIC in patients with metabolic
diseases need to be assessed on an individual basis.
PMID- 28694009
TI - Role of dual red imaging to guide intravariceal sclerotherapy injection of
esophageal varices (with videos).
AB - BACKGROUND AND AIMS: Dual red imaging (DRI) is a novel image-enhanced endoscopy
technique that can increase the visibility and predict the depth of esophageal
varices (EVs). The recurrence rate of EVs after endoscopic injection
sclerotherapy (EIS) reportedly decreases by intravariceal injection of a
sclerosant. We evaluated prospectively whether the EIS success rate was increased
by DRI compared with the white-light imaging (WLI) mode. METHODS: A total of 79
patients with EVs were randomly divided into the DRI (n = 40) and WLI (n = 39)
groups. The primary endpoint was the success rate of intravariceal injection on
the first EIS puncture. The secondary endpoint was the recurrence rate. A
variable puncture needle was used, and the length was adjusted according to the
EV visibility change by DRI. In the WLI group, DRI was not used. RESULTS: The
success rate of the first puncture was significantly higher in the DRI group than
in the WLI group (80.0% vs 46.2%; P = .0018). The cumulative recurrence rate was
significantly lower in the DRI group (P = .031). The sum of the depth and luminal
diameter of EVs was investigated by EUS. The Pearson correlation coefficient
between this value and the needle length was higher in the DRI group than in the
WLI group (r = 0.878 vs 0.603). CONCLUSIONS: DRI increased the EIS success rate
and decreased the recurrence rate. This resulted from the puncture needle
adjustment to the appropriate length via EV depth prediction by DRI.
PMID- 28694010
TI - Right-sided chylothorax following left-sided approach anterior cervical
discectomy and fusion surgery at the C6-7 level.
PMID- 28694011
TI - The relationship between salivary C-reactive protein and cognitive function in
children aged 11-14years: Does psychopathology have a moderating effect?
AB - Elevated C-reactive protein (CRP), a non-specific biomarker of systemic bodily
inflammation, has been associated with more pronounced cognitive impairments in
adults with psychiatric disorders, particularly in the domains of memory and
executive function. Whether this association is present in early life (i.e., the
time at which the cognitive impairments that characterise these disorders become
evident), and is specific to those with emerging psychiatric disorders, has yet
to be investigated. To this end, we examined the association between salivary CRP
and cognitive function in children aged 11-14years and explored the moderating
effect of psychopathology. The study utilised data from an established
longitudinal investigation of children recruited from the community (N=107) that
had purposively over-sampled individuals experiencing psychopathology (determined
using questionnaires). CRP was measured in saliva samples and participants
completed assessments of cognition (memory and executive function) and
psychopathology (internalising and externalising symptoms and psychotic-like
experiences). Linear regression models indicated that higher salivary CRP was
associated with poorer letter fluency (beta=-0.24, p=0.006) and scores on the
inhibition (beta=-0.28, p=0.004) and inhibition/switching (beta=-0.36, p<0.001)
subtests of the colour-word interference test, but not with performance on any of
the memory tasks (working, visual, and verbal memory tasks). Results were largely
unchanged after adjustment for psychopathology and no significant interactions
between CRP and psychopathology were observed on any cognitive measure. Our
findings provide preliminary evidence that elevated salivary CRP is associated
with poorer cognitive function in early life, but that this association is not
moderated by concurrent psychopathology. These findings have implications for
early intervention strategies that attempt to ameliorate cognitive deficits
associated with emerging psychiatric disorders. Further research is needed to
determine whether salivary CRP levels can be used as a valid marker of peripheral
inflammation among healthy adolescents.
PMID- 28694012
TI - Self-injurious behavior.
AB - Self-injurious behavior (SIB) is a relatively common behavior in individuals with
intellectual disabilities (ID). Severe SIB can be devastating and potentially
life-threatening. There is increasing attention for somatic substrates of
behavior in genetic syndromes, and growing evidence of an association between
pain and discomfort with SIB in people with ID and genetic syndromes. In this
review on SIB phenomenology in people with ID in general and in twelve genetic
syndromes, we summarize different SIB characteristics across these etiologically
distinct entities and identify influencing factors. We demonstrate that the
prevalence of SIB in several well-known genetic intellectual disability syndromes
is noticeably higher than in individuals with ID in general, and that
characteristics such as age of onset and topographies differ widely across
syndromes. Each syndrome is caused by a mutation in a different gene, and this
allows detection of several pathways that lead to SIB. Studying these with the
behavioral consequences as specific aim will be an important step toward targeted
early interventions and prevention.
PMID- 28694013
TI - Secondary gastric cancer following a breast cancer diagnosis; beware of
metastatic breast cancer.
PMID- 28694014
TI - De-escalating and escalating systemic therapy of early breast cancer.
PMID- 28694015
TI - Predicting treatment resistance and relapse through circulating DNA.
AB - The use of circulating DNA(ctDNA) to provide a non-invasive, personalised genomic
snapshot of a patients' tumour has huge potential. Over the past five years this
area of research has gained huge momentum. A number of studies in metastatic
breast cancer have shown the potential of ctDNA to predict prognosis and
treatment response using ctDNA. Further developments have included deeper
sequencing using whole exome and shallow whole genome approaches which has the
potential to identify new mutations and chromosomal copy number changes which
appear upon resistance to treatment. In early breast cancer, recent work
utilising personalised digital PCR probes has shown huge potential in predicting
disease relapse and the detection of micrometastatic disease which could lead to
improved treatment and outcome for these patients. Specific pathways of
resistance can also be monitored and liquid biopsy approaches for the detection
of ESR1 mutations have been used which could identify patients who have become
resistant to particular endocrine therapies. The identification of PIK3CA
mutations in plasma has also been shown to predict a higher response rate to
specific PI3K inhibitors and could be used as a non-invasive screening tool prior
to treatment. Further work on the detection of exosomal miRNA and hypermethylated
DNA in plasma have shown promise in terms of specificity for early breast cancer
detection and could be used to monitor treatment response. This review will focus
on technological advances in the field, early detection of relapse and the
detection of tumour-specific genomic alterations which could predict treatment
response and resistance in patients with breast cancer.
PMID- 28694016
TI - [18F]FDOPA positron emission tomography in manganese-exposed workers.
AB - Occupational manganese (Mn) exposure is associated with the development of
parkinsonism; however, the mechanism of neurotoxicity is unknown. Brain positron
emission tomography (PET) imaging provides a non-invasive method of assessing
dopamineric neuronal function. 6-[18F]fluoro-L-DOPA (FDOPA) PET reflects in-vivo
nigrostriatal function, but results in Mn exposure are conflicting. The objective
of this study was to investigate the association between Mn exposure secondary to
occupational welding, FDOPA striatal uptake, and clinical parkinsonism as
measured by Unified Parkinson Disease Rating Scale motor subscore 3 (UPDRS3)
scores. FDOPA PET scans were acquired on 72 subjects (27 Mn-exposed welders, 14
other Mn-exposed workers, and 31 non-exposed subjects). We estimated cumulative
welding exposure from detailed work histories, and a movement disorders
specialist examined all subjects. Striatal volumes of interest were identified on
aligned magnetic resonance imaging (MRI) for each subject. Specific striatal
FDOPA uptake was calculated with a graphical analysis method. We used linear
regression while adjusting for age to assess the association between welding
exposure and FDOPA uptake in the caudate, anterior putamen, and posterior
putamen. Compared to the non-exposed subjects, mean caudate FDOPA uptake was
0.0014min-1 (95% confidence interval [CI] 0.0008, 0.0020) lower in Mn-exposed
welders and 0.0012min-1 (95% CI 0.0005, 0.0019) lower in other Mn-exposed workers
(both p<=0.001). There was no clear dose-response association between caudate
FDOPA uptake and Mn exposure or UPDRS3 scores. Mn-exposed welders and workers
demonstrated lower caudate FDOPA uptake, indicating pre-synaptic dopaminergic
dysfunction in Mn-exposed subjects that was not associated with clinical
parkinsonism.
PMID- 28694017
TI - Multi-frequency interpolation in spiral magnetic resonance fingerprinting for
correction of off-resonance blurring.
AB - Magnetic resonance fingerprinting (MRF) pulse sequences often employ spiral
trajectories for data readout. Spiral k-space acquisitions are vulnerable to
blurring in the spatial domain in the presence of static field off-resonance.
This work describes a blurring correction algorithm for use in spiral MRF and
demonstrates its effectiveness in phantom and in vivo experiments. Results show
that image quality of T1 and T2 parametric maps is improved by application of
this correction. This MRF correction has negligible effect on the concordance
correlation coefficient and improves coefficient of variation in regions of off
resonance relative to uncorrected measurements.
PMID- 28694018
TI - The ENU-3 protein family members function in the Wnt pathway parallel to UNC
6/Netrin to promote motor neuron axon outgrowth in C. elegans.
AB - The axons of the DA and DB classes of motor neurons fail to reach the dorsal cord
in the absence of the guidance cue UNC-6/Netrin or its receptor UNC-5 in C.
elegans. However, the axonal processes usually exit their cell bodies in the
ventral cord in the absence of both molecules. Strains lacking functional
versions of UNC-6 or UNC-5 have a low level of DA and DB motor neuron axon
outgrowth defects. We found that mutations in the genes for all six of the ENU-3
proteins function to enhance the outgrowth defects of the DA and DB axons in
strains lacking either UNC-6 or UNC-5. A mutation in the gene for the MIG
14/Wntless protein also enhances defects in a strain lacking either UNC-5 or UNC
6, suggesting that the ENU-3 and Wnt pathways function parallel to the Netrin
pathway in directing motor neuron axon outgrowth. Our evidence suggests that the
ENU-3 proteins are novel members of the Wnt pathway in nematodes. Five of the six
members of the ENU-3 family are predicted to be single-pass trans-membrane
proteins. The expression pattern of ENU-3.1 was consistent with plasma membrane
localization. One family member, ENU-3.6, lacks the predicted signal peptide and
the membrane-spanning domain. In HeLa cells ENU-3.6 had a cytoplasmic
localization and caused actin dependent processes to appear. We conclude that the
ENU-3 family proteins function in a pathway parallel to the UNC-6/Netrin pathway
for motor neuron axon outgrowth, most likely in the Wnt pathway.
PMID- 28694019
TI - Opportunities to Reduce Diabetes Risk in Women of Reproductive Age: Assessment
and Treatment of Prediabetes within a Large Integrated Delivery System.
AB - BACKGROUND: Preventing diabetes before pregnancy may be important to improve
maternal and infant outcomes. Although the preconception period is a crucial time
to focus on chronic disease prevention, little is known about preventive services
for reproductive-aged women at risk of developing diabetes. METHODS: Using
electronic health record data from patients at Kaiser Permanente Northern
California, we identified 21,965 nonpregnant women aged 18 to 44 with incident
prediabetes (PDM; fasting plasma glucose [FPG] = 100-125 or glycated hemoglobin
A1c = 5.7%-6.4%) between 2007 and 2010. We looked for evidence of a "clinical
response" to PDM in the 6 months after laboratory testing, defined as retesting
of blood glucose levels, referral or attendance to health education, diagnosis of
PDM, metformin initiation, or a clinical note of discussion of PDM. Multilevel
models were used to examine the relationship between patient characteristics and
clinical response, and to assess provider-level variation. RESULTS: Fewer than
one-half of women had a documented clinical response to the PDM-range laboratory
result. Women with higher FPG values and body mass indexes were more likely to
have a PDM diagnosis (FPG 120-125 vs. 100-119: OR, 1.96; 95% CI, 1.78-2.17; body
mass index, 30-34 kg/m2 vs. <25 kg/m2: OR, 1.30; 95% CI, 1.13-1.48) and have
'PDM' recorded in the notes (FPG 120-125 vs. 100-119: OR, 1.15; 95% CI, 1.06
1.26; body mass index: 30-34 kg/m2 vs. <25 kg/m2: OR, 1.58; 95% CI, 1.44-1.74).
Provider-level variation was modest, except for metformin initiation (intraclass
correlation coefficient, 0.8; p < .01). CONCLUSIONS: Low clinical response to PDM
among women of reproductive age suggests there are missed opportunities for
diabetes prevention among this vulnerable population.
PMID- 28694020
TI - Transdifferentiation of brain-derived neurotrophic factor (BDNF)-secreting
mesenchymal stem cells significantly enhance BDNF secretion and Schwann cell
marker proteins.
AB - The use of genetically modified mesenchymal stem cells (MSCs) is a rapidly
growing area of research targeting delivery of therapeutic factors for neuro
repair. Cells can be programmed to hypersecrete various growth/trophic factors
such as brain-derived neurotrophic factor (BDNF), glial cell line-derived
neurotrophic factor (GDNF), and nerve growth factor (NGF) to promote regenerative
neurite outgrowth. In addition to genetic modifications, MSCs can be subjected to
transdifferentiation protocols to generate neural cell types to physically and
biologically support nerve regeneration. In this study, we have taken a novel
approach by combining these two unique strategies and evaluated the impact of
transdifferentiating genetically modified MSCs into a Schwann cell-like
phenotype. After 8 days in transdifferentiation media, approximately 30-50% of
transdifferentiated BDNF-secreting cells immunolabeled for Schwann cell markers
such as S100beta, S100, and p75NTR. An enhancement was observed 20 days after
inducing transdifferentiation with minimal decreases in expression levels. BDNF
production was quantified by ELISA, and its biological activity tested via the
PC12-TrkB cell assay. Importantly, the bioactivity of secreted BDNF was verified
by the increased neurite outgrowth of PC12-TrkB cells. These findings demonstrate
that not only is BDNF actively secreted by the transdifferentiated BDNF-MSCs, but
also that it has the capacity to promote neurite sprouting and regeneration.
Given the fact that BDNF production remained stable for over 20 days, we believe
that these cells have the capacity to produce sustainable, effective, BDNF
concentrations over prolonged time periods and should be tested within an in vivo
system for future experiments.
PMID- 28694021
TI - Recombinant and chemo-/bio-orthogonal synthesis of liposomal thrombomodulin and
its antithrombotic activity.
AB - Thrombomodulin (TM) is an endothelial cell membrane protein that acts as a major
cofactor in the protein C anticoagulant pathway. The EGF-like domains 4-6 of TM
(TM456) are essential for PC activation. In this study, we proposed a liposomal
recombinant TM conjugate to mimic the membrane TM structure and its anticoagulant
activity. First, a DSPE-PEG2000-TM456 was successfully synthesized by site
specific conjugation of azido-TM456 with DSPE-PEG2000-DBCO via copper-free click
chemistry quantitatively. Then, liposome-TM456 was fabricated via direct liposome
formation with the DSPE-PEG2000-TM456 and other lipids. This liposomal
formulation of TM456 retained protein C activation activity as that of TM456.
Also, liposome-TM456 was much more stable and had a longer plasma half-life than
TM456 and DSPE-PEG2000-TM456, respectively. Moreover, liposome-TM456 showed in
vivo anticoagulant effect by decreasing the mortality from 80% to 20% in a
thrombin-induced thromboembolism mouse model. The reported liposome-TM456
conjugate mimics the endothelial TM anticoagulation activity and may serve as an
effective anticoagulant agent candidate for future development.
PMID- 28694022
TI - The clinical utility of repetitive transcranial magnetic stimulation in reducing
the risks of transitioning from acute to chronic pain in traumatically injured
patients.
AB - Pain is a multifaceted condition and a major ongoing challenge for healthcare
professionals having to treat patients in whom pain put them at risk of
developing other conditions. Significant efforts have been invested in both
clinical and research settings in an attempt to demystify the mechanisms at stake
and develop optimal treatments as well as to reduce individual and societal
costs. It is now universally accepted that neuroinflammation and central
sensitization are two key underlying factors causing pain chronification as they
result from maladaptive central nervous system plasticity. Recent research has
shown that the mechanisms of action of repetitive transcranial magnetic
stimulation (rTMS) make it a particularly promising avenue in treating various
pain conditions. This review will first discuss the contribution of
neuroinflammation and central sensitization in the transition from acute to
chronic pain in traumatically injured patients. A detailed discussion on how rTMS
may allow the restoration from maladaptive plasticity in addition to breaking
down the chain of events leading to pain chronification will follow. Lastly, this
review will provide a theoretical framework of what might constitute optimal rTMS
modalities in dealing with pain symptoms in traumatically injured patients based
on an integrated perspective of the physiopathological mechanisms underlying
pain.
PMID- 28694023
TI - Reactivity toward Bifidobacterium longum and Enterococcus hirae demonstrate
robust CD8+ T cell response and better prognosis in HBV-related hepatocellular
carcinoma.
AB - Recent studies suggest that several bacterial species are involved in tumor
immunosurveillance and antitumor immunity. The role of bacteria in immune
responses in HBV-related hepatocellular carcinoma (HCC) patients is still
unknown. In this study, we examined the bacteria-reactive CD8+ T cell response in
patients with HBV-related HCC. We found that circulating CD8+ T cells from
healthy individuals demonstrated minimal or zero specificity toward a series of
commensals and bacteria previously associated with antitumor effects, including
Escherichia coli, Enterococcus faecium, Bifidobacterium longum, Bacteroides
fragilis, and Enterococcus hirae. In contrast, the circulating CD8+ T cells from
HBV-related HCC patients presented significantly elevated bacteria-reactive
responses, albeit with high variations among different HCC individuals.
Reactivity toward bacteria was also identified in tumor-infiltrating CD8+ T
cells. These bacteria-reactive responses were not primarily induced by TLR
ligand, but were dependent on the presence of antigen-presenting monocytes, and
were MHC class I-restricted. Interestingly, we observed that the CD8+ T cell-to
Foxp3+ regulatory T cell ratio was positively correlated with the proportions of
Bifidobacterium longum-reactive and Enterococcus hirae-reactive CD8+ T cells,
while the frequency of PD-1+ CD8+ T cells was negatively correlated with the
frequency of Enterococcus hirae-reactive CD8+ T cells. Furthermore, the disease
free survival time of HCC patients after tumor resection was positively
correlated with the frequencies of Bifidobacterium longum-reactive and
Enterococcus hirae-reactive CD8+ T cells. Together, these results suggested that
certain bacterial species might present valuable antitumor effects.
PMID- 28694024
TI - Iron metabolism: State of the art.
AB - Iron homeostasis relies on the amount of its absorption by the intestine and its
release from storage sites, the macrophages. Iron homeostasis is also dependent
on the amount of iron used for the erythropoiesis. Hepcidin, which is synthesized
predominantly by the liver, is the main regulator of iron metabolism. Hepcidin
reduces serum iron by inhibiting the iron exporter, ferroportin expressed both
tissues, the intestine and the macrophages. In addition, in the enterocytes,
hepcidin inhibits the iron influx by acting on the apical transporter, DMT1. A
defect of hepcidin expression leading to the appearance of a parenchymal iron
overload may be genetic or secondary to dyserythropoiesis. The exploration of
genetic hemochromatosis has revealed the involvement of several genes, including
the recently described BMP6. Non-transfusional secondary hemochromatosis is due
to hepcidin repression by cytokines, in particular the erythroferone factor that
is produced directly by the erythroid precursors. Iron overload is correlated
with the appearance of a free form of iron called NTBI. The influx of NTBI seems
to be mediated by ZIP14 transporter in the liver and by calcium channels in the
cardiomyocytes. Beside the liver, hepcidin is expressed at lesser extent in
several extrahepatic tissues where it plays its ancestral role of antimicrobial
peptide. In the kidney, hepcidin modulates defense barriers against urinary tract
infections. In the heart, hepcidin maintains tissue iron homeostasis by an
autocrine regulation of ferroprotine expression on the surface of cardiomyocytes.
In conclusion, hepcidin remains a promising therapeutic tool in various iron
pathologies.
PMID- 28694025
TI - The potential of viral metagenomics in blood transfusion safety.
AB - Thanks to the significant advent of high throughput sequencing in the last ten
years, it is now possible via metagenomics to define the spectrum of the
microbial sequences present in human blood samples. Therefore, metagenomics
sequencing appears as a promising approach for the identification and global
surveillance of new, emerging and/or unexpected viruses that could impair blood
transfusion safety. However, despite considerable advantages compared to the
traditional methods of pathogen identification, this non-targeted approach
presents several drawbacks including a lack of sensitivity and sequence
contaminant issues. With further improvements, especially to increase
sensitivity, metagenomics sequencing should become in a near future an additional
diagnostic tool in infectious disease field and especially in blood transfusion
safety.
PMID- 28694026
TI - Nano-technology based carriers for nitrogen-containing bisphosphonates delivery
as sensitisers of gammadelta T cells for anticancer immunotherapy.
AB - Nitrogen containing bisphosphonates (N-BPs) including zoledronate (ZOL) and
alendronate (ALD) inhibit farnesyl diphosphate synthase, and have been shown to
have a cytotoxic affect against cancer cells as a monotherapy and to also
sensitise tumour cells to destruction by gammadelta T cells. gammadelta T cells
are a subset of human T lymphocytes and have a diverse range of roles in the
immune system including the recognition and destruction of cancer cells. This
property of gammadelta T cells can be harnessed for use in cancer immunotherapy
through in vivo expansion or the adoptive transfer of ex vivo activated
gammadelta T cells. The use of N-BPs with gammadelta T cells has been shown to
have a synergistic effect in in vitro, animal and clinical studies. N-BPs have
limited in vivo activity due to rapid clearance from the circulation. By
encapsulating N-BPs in liposomes (L) it is possible to increase the levels of N
BPs at non-osseous tumour sites. L-ZOL and L-ALD have been shown to have
different toxicological profiles than free ZOL or ALD. Both L-ALD and L-ZOL led
to increased spleen weight, leucocytosis, neutrophilia and lymphocytopenia in
mice after intravenous injection. L-ALD was shown to be better tolerated than L
ZOL in murine studies. Biodistribution studies have been performed in order to
better understand the interaction of N-BPs and gammadelta T cells in vivo.
Additionally, in vivo therapy studies have shown that mice treated with both L
ALD and gammadelta T cells had a significant reduction in tumour growth compared
to mice treated with L-ALD or gammadelta T cells alone. The use of ligand
targeted liposomes may further increase the efficacy of this combinatory
immunotherapy. Liposomes targeting the alphavbeta6 integrin receptor using the
peptide A20FMDV2 had a greater ability than untargeted liposomes in sensitising
cancer cells to destruction by gammadelta T cells in alphavbeta6 positive cancer
cell lines.
PMID- 28694028
TI - The pivotal role of extracellular signal-regulated kinase in gap junction
mediated regulation of TXNIP.
AB - Gap junctions (GJs) play a major role in the control of cell structure, function,
and metabolism. However, the molecular mechanisms involved are still poorly
understood. Given that thioredoxin-interacting protein (TXNIP) regulates a broad
range of cellular processes, we tested the possible involvement of TXNIP.
Disruption of GJs with several chemical GJ inhibitors or connexin43 (Cx43) siRNA
potently suppressed TXNIP, which was preceded by an activation of extracellular
signal-regulated kinase (ERK). Inhibition of ERK or its upstream kinase with
chemical inhibitors prevented the reduction of TXNIP. On the contrary, activation
of ERK with mitogens or phosphatase inhibitors reproduced the suppressive effects
of GJs. Further analysis revealed that dysfunction of GJs promoted TXNIP
phosphorylation, ubiquitination, and degradation, whereas inhibition of ERK
exerted the opposite effects. Moreover, inhibition of GJs elevated Glut1 and
enhanced cell resistance to ER stress in a similar way to TXNIP downregulation.
Collectively, our study thus characterizes ERK-mediated suppression of TXNIP as a
presently unreported mechanism by which GJs regulate cell behaviors.
PMID- 28694029
TI - Medical capsule robots: A renaissance for diagnostics, drug delivery and surgical
treatment.
AB - The advancements in electronics and the progress in nanotechnology have resulted
in path breaking development that will transform the way diagnosis and treatment
are carried out currently. This development is Medical Capsule Robots, which has
emerged from the science fiction idea of robots travelling inside the body to
diagnose and cure disorders. The first marketed capsule robot was a capsule
endoscope developed to capture images of the gastrointestinal tract. Today,
varieties of capsule endoscopes are available in the market. They are slightly
larger than regular oral capsules, made up of a biocompatible case and have
electronic circuitry and mechanisms to capture and transmit images. In addition,
robots with diagnostic features such as in vivo body temperature detection and pH
monitoring have also been launched in the market. However, a multi-functional
unit that will diagnose and cure diseases inside the body has not yet been
realized. A remote controlled capsule that will undertake drug delivery and
surgical treatment has not been successfully launched in the market. High cost,
inadequate power supply, lack of control over drug release, limited space for
drug storage on the capsule, inadequate safety and no mechanisms for active
locomotion and anchoring have prevented their entry in the market. The capsule
robots can revolutionize the current way of diagnosis and treatment. This paper
discusses in detail the applications of medical capsule robots in diagnostics,
drug delivery and surgical treatment. In diagnostics, detailed analysis has been
presented on wireless capsule endoscopes, issues associated with the marketed
versions and their corresponding solutions in literature. Moreover, an assessment
has been made of the existing state of remote controlled capsules for targeted
drug delivery and surgical treatment and their future impact is predicted.
Besides the need for multi-functional capsule robots and the areas for further
research have also been highlighted.
PMID- 28694027
TI - Exploiting lymphatic vessels for immunomodulation: Rationale, opportunities, and
challenges.
AB - Lymphatic vessels are the primary route of communication from peripheral tissues
to the immune system; as such, they represent an important component of local
immunity. In addition to their transport functions, new immunomodulatory roles
for lymphatic vessels and lymphatic endothelial cells have come to light in
recent years, demonstrating that lymphatic vessels help shape immune responses in
a variety of ways: promoting tolerance to self-antigens, archiving antigen for
later presentation, dampening effector immune responses, and resolving
inflammation, among others. In addition to these new biological insights, the
growing field of immunoengineering has begun to explore therapeutic approaches to
utilize or exploit the lymphatic system for immunotherapy.
PMID- 28694030
TI - Antimicrobial peptide-gold nanoscale therapeutic formulation with high skin
regenerative potential.
AB - Chronic skin wounds affect ~3% of persons aged >60years (Davies et al., 2007)
[1]. These wounds are typically difficult to heal by conventional therapies and
in many cases they get infected making even harder the regeneration process. The
antimicrobial peptide (AMP) LL37 combines antimicrobial with pro-regenerative
properties and thus represents a promising topical therapy to address both
problems. Here, we investigated the wound healing potential of soluble and
immobilized LL37 (LL37-conjugated gold nanoparticles, LL37-Au NPs), both in vitro
(migration of keratinocytes) and in vivo (skin wound healing). Our results show
that LL37-Au NPs, but not LL37 peptide, have the capacity to prolong the
phosphorylation of EGFR and ERK1/2 and enhance the migratory properties of
keratinocytes in a large in vitro wound model. We further report that both LL37
and LL37-Au NPs promote keratinocyte migration by the transactivation of EGFR, a
process that seems to be initiated at the P2X7 receptor, as confirmed by chemical
and genetic inhibition studies. Finally, we show in vivo that LL37-Au NPs have
higher wound healing activity than LL37 peptide in a splinted mouse full
thickness excisional model. Animal wounds treated by LL37-Au NPs have higher
expression of collagen, IL6 and VEGF than the ones treated with LL37 peptide or
NPs without LL37. Altogether, the conjugation of AMPs to NPs offers a promising
platform to enhance their pro-regenerative properties.
PMID- 28694031
TI - In vivo induction of regulatory T cells promotes allergen tolerance and
suppresses allergic contact dermatitis.
AB - Allergic contact dermatitis (ACD) is a common T-cell mediated inflammatory skin
condition, characterized by an intensely pruritic rash at the site of contact
with allergens like poison ivy or nickel. Current clinical treatments use topical
corticosteroids, which broadly and transiently suppress inflammation and symptoms
of ACD, but fail to address the underlying immune dysfunction. Here, we present
an alternative therapeutic approach that teaches the immune system to tolerate
contact allergens by expanding populations of naturally suppressive allergen
specific regulatory T cells (Tregs). Specifically, biodegradable poly(ethylene
glycol)-poly(lactic-co-glycolic acid) (PEG-PLGA) microparticles were engineered
to release TGF-beta1, Rapamycin, and IL-2, to locally sustain a microenvironment
that promotes Treg differentiation. By expanding allergen-specific Tregs and
reducing pro-inflammatory effector T cells, these microparticles inhibited
destructive hypersensitivity responses to subsequent allergen exposure in an
allergen-specific manner, effectively preventing or reversing ACD in previously
sensitized mice. Ultimately, this approach to in vivo Treg induction could also
enable novel therapies for transplant rejection and autoimmune diseases.
PMID- 28694032
TI - Biodegradable brain-penetrating DNA nanocomplexes and their use to treat
malignant brain tumors.
AB - The discovery of powerful genetic targets has spurred clinical development of
gene therapy approaches to treat patients with malignant brain tumors. However,
lack of success in the clinic has been attributed to the inability of
conventional gene vectors to achieve gene transfer throughout highly disseminated
primary brain tumors. Here, we demonstrate ex vivo that small nanocomplexes
composed of DNA condensed by a blend of biodegradable polymer, poly(beta-amino
ester) (PBAE), with PBAE conjugated with 5kDa polyethylene glycol (PEG) molecules
(PBAE-PEG) rapidly penetrate healthy brain parenchyma and orthotopic brain tumor
tissues in rats. Rapid diffusion of these DNA-loaded nanocomplexes observed in
fresh tissues ex vivo demonstrated that they avoided adhesive trapping in the
brain owing to their dense PEG coating, which was critical to achieving
widespread transgene expression throughout orthotopic rat brain tumors in vivo
following administration by convection enhanced delivery. Transgene expression
with the PBAE/PBAE-PEG blended nanocomplexes (DNA-loaded brain-penetrating
nanocomplexes, or DNA-BPN) was uniform throughout the tumor core compared to
nanocomplexes composed of DNA with PBAE only (DNA-loaded conventional
nanocomplexes, or DNA-CN), and transgene expression reached beyond the tumor
edge, where infiltrative cancer cells are found, only for the DNA-BPN
formulation. Finally, DNA-BPN loaded with anti-cancer plasmid DNA provided
significantly enhanced survival compared to the same plasmid DNA loaded in DNA-CN
in two aggressive orthotopic brain tumor models in rats. These findings
underscore the importance of achieving widespread delivery of therapeutic nucleic
acids within brain tumors and provide a promising new delivery platform for
localized gene therapy in the brain.
PMID- 28694033
TI - Drug depot-anchoring hydrogel: A self-assembling scaffold for localized drug
release and enhanced stem cell differentiation.
AB - Localized and long-term delivery of growth factors has been a long-standing
challenge for stem cell-based tissue engineering. In the current study, a
polymeric drug depot-anchoring hydrogel scaffold was developed for the sustained
release of macromolecules to enhance the differentiation of stem cells. Self
assembling peptide (RADA16)-modified drug depots (RDDs) were prepared and
anchored to a RADA16 hydrogel. The anchoring effect of RADA16 modification on the
RDDs was tested both in vitro and in vivo. It was shown that the in vitro leakage
of RDDs from the RADA16 hydrogel was significantly less than that of the
unmodified drug depots (DDs). In addition, the in vivo retention of injected
hydrogel-incorporated RDDs was significantly longer than that of hydrogel
incorporated unmodified DDs. A model drug, vascular endothelial growth factor
(VEGF), was encapsulated in RDDs (V-RDDs) as drug depot that was then anchored to
the hydrogel. The release of VEGF could be sustained for 4weeks. Endothelial
progenitor cells (EPCs) were cultured on the V-RDDs-anchoring scaffold and
enhanced cell proliferation and differentiation were observed, compared with a
VEGF-loaded scaffold. Furthermore, this scaffold laden with EPCs promoted
neovascularization in an animal model of hind limb ischemia. These results
demonstrate that self-assembling hydrogel-anchored drug-loaded RDDs are promising
for localized and sustained drug release, and can effectively enhance the
proliferation and differentiation of resident stem cells, thus lead to successful
tissue regeneration.
PMID- 28694034
TI - Insertion-and-deletion-derived tumour-specific neoantigens and the immunogenic
phenotype: a pan-cancer analysis.
AB - BACKGROUND: The focus of tumour-specific antigen analyses has been on single
nucleotide variants (SNVs), with the contribution of small insertions and
deletions (indels) less well characterised. We investigated whether the
frameshift nature of indel mutations, which create novel open reading frames and
a large quantity of mutagenic peptides highly distinct from self, might
contribute to the immunogenic phenotype. METHODS: We analysed whole-exome
sequencing data from 5777 solid tumours, spanning 19 cancer types from The Cancer
Genome Atlas. We compared the proportion and number of indels across the cohort,
with a subset of results replicated in two independent datasets. We assessed in
silico tumour-specific neoantigen predictions by mutation type with pan-cancer
analysis, together with RNAseq profiling in renal clear cell carcinoma cases
(n=392), to compare immune gene expression across patient subgroups. Associations
between indel burden and treatment response were assessed across four checkpoint
inhibitor datasets. FINDINGS: We observed renal cell carcinomas to have the
highest proportion (0.12) and number of indel mutations across the pan-cancer
cohort (p<2.2 * 10-16), more than double the median proportion of indel mutations
in all other cancer types examined. Analysis of tumour-specific neoantigens
showed that enrichment of indel mutations for high-affinity binders was three
times that of non-synonymous SNV mutations. Furthermore, neoantigens derived from
indel mutations were nine times enriched for mutant specific binding, as compared
with non-synonymous SNV derived neoantigens. Immune gene expression analysis in
the renal clear cell carcinoma cohort showed that the presence of mutant-specific
neoantigens was associated with upregulation of antigen presentation genes, which
correlated (r=0.78) with T-cell activation as measured by CD8-positive
expression. Finally, analysis of checkpoint inhibitor response data revealed
frameshift indel count to be significantly associated with checkpoint inhibitor
response across three separate melanoma cohorts (p=4.7 * 10-4). INTERPRETATION:
Renal cell carcinomas have the highest pan-cancer proportion and number of indel
mutations. Evidence suggests indels are a highly immunogenic mutational class,
which can trigger an increased abundance of neoantigens and greater mutant
binding specificity. FUNDING: Cancer Research UK, UK National Institute for
Health Research (NIHR) at the Royal Marsden Hospital National Health Service
Foundation Trust, Institute of Cancer Research and University College London
Hospitals Biomedical Research Centres, the UK Medical Research Council, the
Rosetrees Trust, Novo Nordisk Foundation, the Prostate Cancer Foundation, the
Breast Cancer Research Foundation, the European Research Council.
PMID- 28694035
TI - Assessment of the ITMIG Statement on the WHO Histological Classification and of
the Eighth TNM Staging of Thymic Epithelial Tumors of a Series of 188 Thymic
Epithelial Tumors.
AB - INTRODUCTION: Thymic epithelial tumors (TETs) are rare intrathoracic malignancies
that are categorized histologically according to the WHO classification, which
was recently updated in 2015 on the basis of a consensus statement of the
International Thymic Malignancy Interest Group (ITMIG); at the same time, the
standard Masaoka-Koga staging system is scheduled to be replaced by the eighth
edition of the TNM staging classification by the American Joint Committee on
Cancer/Union for International Cancer Control consortium. Our objectives were to
analyze the feasibility of assessing ITMIG consensus major and minor
morphological and immunohistochemical criteria and the eighth edition of the TNM
staging classification in a routine practice setting. METHODS: This is a single
center study conducted at the Louis-Pradel Hospital of Lyon University, one of
the largest centers for TETs in France. Overall, a large surgical series of 188
TETs diagnosed in 181 patients between 2000 and 2014 at our center were analyzed.
RESULTS: There were 89 men (49%) and 92 women (51%); 57 patients (31%) presented
with myasthenia gravis at time of diagnosis. According to the WHO classification,
there were nine type A thymomas (5%), 67 type AB thymomas (36%), 19 type B1
thymomas (10%), 46 type B2 thymomas (24%), 27 type B3 thymomas (14%), and 20
thymic carcinomas (11%). ITMIG consensus major criteria were identified in 100%
of type A, AB, B1, and B2 thymomas. After restaging according to the eighth
edition of the TNM staging classification, there were 127 stage I (84%), three
stage II (2%), 17 stage IIIa (11%), no stage IIIb, two stage IVa (1%), and three
stage IVb (2%) thymomas. Significant correlation between histological type and
stage at diagnosis was maintained after restaging according the TNM
classification. CONCLUSION: Comprehensive analysis of our well-characterized
surgical series of 188 TETs indicates the feasibility and the diagnostic value of
the ITMIG consensus statement on WHO histological classification and highlights
the major switch in staging when the eighth edition of the TNM staging
classification is applied.
PMID- 28694036
TI - [Priority setting and rationing of pharmaceuticals - an experimental analysis of
discussion processes].
AB - BACKGROUND/OBJECTIVE: In the face of rising expenditure among statutory sickness
funds in Germany it is necessary to start a discussion about priority setting in
the healthcare system. For a long time this issue has been avoided in healthcare
debates. As a result, normative directives are still missing, which can lead to
priority setting among healthcare providers in daily healthcare practice.
Prioritization can be conducted at three different levels: at the government
(macro), the institutional (meso), and the patient (micro) level. Surveys about
societal preferences for different criteria exist; however, specifications on
their respective weighting in the situation of approval and reimbursement of
pharmaceuticals (meso) are missing. For this reason, the present study analyzed
the implementation and weighting of the criteria for priority setting at the meso
level, taking values and experiences of the participants into account. METHOD:
Six qualitative focus groups were carried out with representatives from the
fields of medicine, ethics, public health and economics. During the discussions
four fictitious drugs for the treatment of different lung diseases were
prioritized based on guidelines. The discussion processes were analyzed according
to Bohnsack's documentary method. RESULTS: The criteria "quality of life", "life
expectancy" and "other patient-relevant outcomes" were discussed in relation to
each other. The evaluation of change in patient-relevant outcomes was difficult
to perform for non-medical participants. The second argument concerned the
criteria "costs", disease severity and "number of patients". Costs were given
less weight, but were often used to support other criteria. Other challenges in
reaching a consensus included emerging role conflicts between profession and
personal opinion, and the transfer of the discussion to a different level of
decision-making. DISCUSSION: In the discussions the problem of prioritizing did
not arise from different preferences for prioritization criteria, but from the
weighting of the criteria. The operationalization of the criteria seemingly
depends on the decision-making situation, the participants' personal connection
with the relevant disease and on the correspondence between evidence and personal
experiences.
PMID- 28694037
TI - Association between gastrointestinal bleeding and 3-year mortality in patients
with acute, first-ever ischemic stroke.
AB - The influence of gastrointestinal bleeding on clinical presentation and outcomes
of patients with acute ischemic stroke remains controversial. We investigate the
effect of gastrointestinal bleeding on the outcomes of patients with acute, first
ever ischemic stroke. We enrolled 934 patients with acute, first-ever ischemic
stroke and followed up them for 3years. Patients were divided into 2 groups
according to the presence or absence of gastrointestinal bleeding during acute
stroke stage. Clinical presentation, stroke risk factors, laboratory data, co
morbidities, and outcomes were recorded. Seventy-six (8.1%) patients had
gastrointestinal bleeding at admission. The prevalence of old age, atrial
fibrillation, and previous transient ischemic attack was higher in patients with
gastrointestinal bleeding (P<0.001, P=0.038, and P=0.018, respectively). Total
anterior circulation syndrome occurred more frequently among patients with
gastrointestinal bleeding (P<0.001). The mean length of acute ward stay, initial
impaired consciousness, and stroke in evolution were higher in patients with
gastrointestinal bleeding (P<0.001, P<0.001, and P<0.001, respectively). The
occurrence of pneumonia and dependent functional outcome were higher in patients
with gastrointestinal bleeding (P<0.001 and P<0.001, respectively). A
multivariate Cox regression analysis revealed that gastrointestinal bleeding is a
significant risk factor for 3-year all-cause mortality (hazard ratio=2.76; 95%
confidence interval=1.61-4.72; P<0.001). In conclusion, gastrointestinal bleeding
is associated with increased risk of 3-year mortality in patients with acute,
first-ever ischemic stroke. Prophylactic therapies for gastrointestinal bleeding
might improve ischemic stroke outcome.
PMID- 28694038
TI - E-learning in neurology education: Principles, opportunities and challenges in
combating neurophobia.
AB - Neurophobia, the fear of clinical neurology, affects not only medical students
but also non-career neurologists globally. This can have significant implications
on patient care, especially given the increasing burden of chronic neurological
disorders. The negative perception and lack of confidence amongst general
practitioners and hospital physicians may lead to increased referrals to
neurology, thereby increasing waiting times and inpatient stay. The onus,
therefore, should be on improving training and stimulating interest in neurology.
There is emerging evidence that integrating e-learning to traditional pedagogies
can improve delivery of neurology education and help combat neurophobia. However,
embracing e-learning may be challenging for contemporary neurologists, mostly
'digital immigrants', involved in the training of tomorrow's doctors who are
largely 'digital natives'. This paper reviews the principles, opportunities and
challenges of incorporating e-learning in neurology education to help improve
learners' perception of clinical neurology, facilitate delivery of self-directed
experiential learning and perhaps breed 'neurophilia'.
PMID- 28694039
TI - Perioperative stroke as a predictor of mortality and morbidity in patients
undergoing CABG.
AB - Perioperative stroke is a devastating neurological complication of Coronary
Artery Bypass Grafting surgery (CABG). It results in significantly increased
rates of mortality and morbidity and presents a significant financial burden to
our healthcare system. It has not, however, been studied in a large population
based sample. We aim to investigate the role of perioperative stroke as an
independent risk factor for in-hospital mortality and morbidity following CABG,
and to review trends in the early outcomes of CABG from the years 1999 to 2011.
We hypothesize that perioperative stroke is an independent risk factor for in
hospital mortality and morbidity following CABG. We analyzed data from the 1999
2011 Nationwide Inpatient Sample, identifying patients who underwent CABG using
ICD-9 and CCS codes. We excluded patients below the age of 18 and above the age
of 100, and patients undergoing concomitant heart and/or vascular procedures.
Analysis on our sample of 668,627 patients yielded an overall rate of
perioperative stroke, mortality, and morbidity of 1.87%, 2.13%, and 49.07%,
respectively. Along with age, risk category, gender, and other postoperative
outcomes, perioperative stroke was found to be a strong predictor of mortality
and morbidity, leading to more than a 5-fold risk of death and morbidity. From
our study, we conclude that perioperative stroke remains a serious adverse
outcome of CABG and is an independent predictor of mortality and morbidity. While
rates of stroke and mortality are decreasing, morbidity continues to trend
upwards. This study emphasizes the importance of prevention and early
intervention in patients at risk for perioperative stroke.
PMID- 28694040
TI - The effect of anxiety and depression on the risk of irritable bowel syndrome in
migraine patients.
AB - Bidirectional co-morbidity between migraine and depression has been observed.
Mood disorders are associated with an increased risk of both migraine and
irritable bowel syndrome (IBS). The aim of this study was to evaluate the risk of
developing IBS in patients with migraine and to compare the risks between those
with and without anxiety or depression. This research used the data contained in
the National Health Insurance Research Database (NHIRD). A total of 2859 subjects
with migraine and 5718 age-, sex-, hypertension-, diabetes-, mood disorder
matched controls were identified. Both cohorts excluded subjects with pre
existing catastrophic illness and IBS diagnosed before the index visit or within
30days after the index visit. All individuals of both cohorts were tracked until
either having the diagnosis of IBS, loss of follow-up, or IBS free up to 7years.
During the 7-year follow-up period, 8.4% of patients with migraine and 5.4% of
control cohort developed IBS. Migraine is associated with an increased risk of
developing IBS (HR=1.58, 95% CI: 1.33-1.87). When separating the cohort into
those with mood disorder and without it, migraine is a significant risk factor of
IBS in patients without mood disorders, but not in patients with co-existed mood
disorders. The findings of this study suggest that migraine is a risk factor of
future IBS development for those without comorbid anxiety or depression. However,
migraine does not contribute significantly additional risk to IBS development in
patients with comorbid anxiety or depression.
PMID- 28694041
TI - Real-time three-dimensional (3D) visualization of fusion image for accurate
subdural electrodes placement of epilepsy surgery.
AB - INTRODUCTION: The perfect match between pre-surgical estimated seizure onset zone
and subdural electrodes (SEs) position is requested for epilepsy surgery.
However, post-surgical neuro images sometimes disappoint physicians due to SEs
malposition. To place SEs, we used to use intraoperative photograph and
fluoroscopy. With this procedure, we just recognized approximate location of SEs
during surgery. The purpose of the study is to perform precise SEs location
intraoperatively using intra operative computer tomography (CT) and image
guidance. PATIENTS AND METHODS: There were 12 patients with intractable epilepsy.
The age ranged from 5years old to 42years old. They underwent SEs placement. The
patients intraoperatively underwent brain CT. Their CT images were automatically
fused onto their 3D magnetic resonance image (MRI) brain image at the monitor of
the image-guidance. In case of malposition or under coverage, neurosurgeons
revised or add SEs along with advice of epileptologists and neurophysiologists.
RESULT: Patients underwent intraoperative CT scans once to three times.
Epileptologists, neurophysiologists and surgeons could intraoperatively recognize
the relationship between the SEs and the 3D MRI brain surface. We could
intraoperatively discuss the localization of SEs and correct the position or add
more SEs to cover estimated seizure onset zone along with real-time visualized
image. We could avoid postoperative malposition of the SEs, so there were no
another SEs operation for revision. CONCLUSION: The intraoperative real-time
visualization of SEs on 3D brain surface image helped us to perform accurate
electrodes placement and could avoid the electrode malposition.
PMID- 28694042
TI - Ruptured choroidal artery aneurysms in patients with moyamoya disease: Two case
series and review of the literatures.
AB - Distal peripheral artery aneurysms in moyamoya disease (MMD) remain difficult to
treat given their deep location, small size, and fragility. Here, we report two
cases of choroidal artery aneurysms associated with MMD who were treated through
direct clipping and coil embolization. Timing of aneurysm formation remains
unclear, however, annual follow-up DSA for surveillance of hemodynamic status is
necessary and prompt treatment of aneurysm should be performed when diagnosed.
Moreover, choroidal artery aneurysms may benefit from endovascular coil
embolization due to their characteristics.
PMID- 28694043
TI - Risk factors and clinical characteristics of non-promyelocytic acute myeloid
leukemia of intracerebral hemorrhage: A single center study in China.
AB - BACKGROUND: Although high mortality in patients with acute leukemia (AL) is
associated with intracranial hemorrhage (ICH), the clinical features and
pathogenesis of AL patients with cerebral hemorrhage are not well known. METHODS:
We diagnosed 90 patients with ICH from a total of 1467 patients with non
promyelocytic AL who had been hospitalized in the First Affiliated Hospital of
Medical School of Zhejiang University from January 2010 to October 2015.
Moreover, the risk factors of ICH death were evaluated. RESULT: Median age at ICH
was 51years old, in which men accounted for 52.2%. They also accounted for 85.6%
of acute myeloid leukemia. The relative incidence of ICH was the highest in M2
and M5 (60.1%). ICH presented with higher peripheral blood white blood cell count
(WBC) (P<0.001), lower peripheral platelet counts (P<0.001), lower albumin
(P<0.001), lower fibrous protein (P<0.001) and prolongation of prothrombin time
(P<0.001) compared to those observed in the patients of NICH group; multivariate
analysis, independent risk factors for death in patients with ICH include:
WBC>=30.00*109/l and prothrombin time>=12.91 s. CONCLUSIONS: Leukocytosis and
coagulation dysfunctions might be the main pathogenesis of acute leukemia
complicated with cerebral hemorrhage.
PMID- 28694044
TI - More randomized and resilient in the topological properties of functional brain
networks in patients with major depressive disorder.
AB - Previous studies have reported the enhanced randomization of functional brain
networks in patients with major depressive disorder (MDD). However, little is
known about the changes of key nodal attributes for randomization, the resilience
of network, and the clinical significance of the alterations. In this study, we
collected the resting-state functional MRI data from 19 MDD patients and 19
healthy control (HC) individuals. Graph theory analysis showed that decreases
were found in the small-worldness, clustering coefficient, local efficiency, and
characteristic path length (i.e., increase of global efficiency) in the network
of MDD group compared with HC group, which was consistent with previous findings
and suggested the development toward randomization in the brain network in MDD.
In addition, the greater resilience under the targeted attacks was also found in
the network of patients with MDD. Furthermore, the abnormal nodal properties were
found, including clustering coefficients and nodal efficiencies in the left
orbital superior frontal gyrus, bilateral insula, left amygdala, right
supramarginal gyrus, left putamen, left posterior cingulate cortex, left angular
gyrus. Meanwhile, the correlation analysis showed that most of these abnormal
areas were associated with the clinical status. The observed increased
randomization and resilience in MDD might be related to the abnormal hub nodes in
the brain networks, which were attacked by the disease pathology. Our findings
provide new evidence to indicate that the weakening of specialized regions and
the enhancement of whole brain integrity could be the potential endophenotype of
the depressive pathology.
PMID- 28694045
TI - Myelitis in systemic lupus erythematosus.
AB - SLE-associated acute transverse myelitis (ATM) is a rare, but potentially severe
complication of Systemic lupus erythematosus (SLE), and may lead to significant
motor, sensory and autonomic dysfunctions in the central nervous system resulting
in marked neurological deficits. It is important to recognize its clinical
feature to allow timely diagnosis and management of this condition. In this
review, we aimed to provide the reader with the understanding of its clinical
presentation and classification, the underlying pathological, MRI (magnetic
resonance imaging) appearance, and current status of management, with an emphasis
on recent discoveries and advancements.
PMID- 28694046
TI - Chronic Eosinophilic Pneumonia: A Diagnostic Challenge.
PMID- 28694047
TI - Sensitization and Exposure to Pets: The Effect on Asthma Morbidity in the US
Population.
AB - BACKGROUND: Although pets are found in more than 50% of US homes, the effect of
pet allergen exposure on asthma morbidity in the US population is not well
documented. OBJECTIVE: To determine the effect of dog and cat allergen exposures
on asthma morbidity in the US population. METHODS: The National Health and
Nutrition Examination Survey is a representative sample of civilian US
population. Data on asthma, dog and cat allergen levels in bedroom dust, as well
as specific IgE to dog and cat were analyzed for all participants 6 years or
older. RESULTS: Pets are common in the United States, with more that 50% of
households having a dog or a cat or both. The prevalence of allergic
sensitization in the National Health and Nutrition Examination Survey population
was similar for dog and cat, with both being approximately 12%. Among those who
were sensitized, exposure to elevated levels of pet allergens was associated with
an increased prevalence of asthma and asthma attacks. Indeed, 44.2% of the asthma
attacks were attributable to exposure to high levels of dog allergen in the
bedroom among patients with asthma sensitive to dog and 30.3% were attributable
to cat allergen exposure among the comparable cat-sensitive and exposed group.
Projecting these results to the US population indicates more than 1 million
increased asthma attacks each year for the dog-sensitive and exposed group and
more than 500,000 increased asthma attacks for the cat-sensitive and exposed
population of patients with asthma. CONCLUSIONS: Exposure to elevated levels of
dog and cat allergens among those sensitized individuals with asthma is
associated with excess asthma attacks. Reducing pet allergen exposures has the
potential for a significant decrease in asthma morbidity.
PMID- 28694048
TI - Evaluation of angiotensin-converting enzyme inhibitor and angiotensin receptor
blocker therapy in immunotherapy-associated systemic reactions.
PMID- 28694049
TI - Nomenclature for factors of the HLA system, update April 2017.
PMID- 28694050
TI - Nomenclature for factors of the HLA system, update June 2017.
PMID- 28694051
TI - Nomenclature for factors of the HLA system, update May 2017.
PMID- 28694052
TI - Group housing during adolescence has long-term effects on the adult stress
response in female, but not male, zebra finches (Taeniopygia guttata).
AB - Adolescent social interactions can have long-term effects on physiological
responses to stressors in later-life. A larger adolescent group size can result
in higher stressor-induced secretion of glucocorticoids in adulthood. The effect
may be due to a socially-mediated modulation of gonadal hormones, e.g.
testosterone. However, group size (number of animals) has been conflated with
social density (space per animal). Therefore it is hard to determine the
mechanisms through which adolescent group size can affect the stress response.
The current study aimed to tease apart the effects of group size and social
density during adolescence on the physiological stress response and gonadal
hormone levels in adulthood. Adolescent zebra finches were housed in groups
varying in size (2 vs. 5 birds per cage) and density (0.03m3 vs. 0.06m3 per bird)
during early adolescence (day 40-60). Density was only manipulated in birds
raised in groups of five. Glucocorticoid concentration secreted in response to a
standard capture and restraint stressor was quantified in adolescence (day 55+/
1) and adulthood (day 100+). Basal gonadal hormone concentrations (male
testosterone, female estradiol) were also quantified in adulthood. Female birds
housed in larger groups, independent of social density, secreted a higher
glucocorticoid concentration 45min into restraint regardless of age, and had
higher peak glucocorticoid concentration in adulthood. Adult gonadal hormone
concentrations were not affected by group size or density. Our results suggest
that group size, not density, is a social condition that influences the
development of the endocrine response to stressors in female zebra finches, and
that these effects persist into adulthood. The findings have clear relevance to
the social housing conditions necessary for optimal welfare in captive animals,
but also elucidate the role of social rearing conditions in the emergence of
responses to stressors that may persist across the lifespan and affect fitness of
animals in wild populations.
PMID- 28694053
TI - Biased signaling of G protein-coupled receptors - From a chemokine receptor CCR7
perspective.
AB - Chemokines (chemotactic cytokines) and their associated G protein-coupled
receptors (GPCRs) work in a concerted manner to govern immune cell positioning in
time and space. Promiscuity of both ligands and receptors, but also biased
signaling within the chemokine system, adds to the complexity of how the cell
based immune system is controlled. Bias comes in three forms; ligand-, receptor-
and tissue-bias. Biased signaling is increasingly being recognized as playing an
important role in contributing to the fine-tuned coordination of immune cell
chemotaxis. In the current review we discuss the recent findings related to
ligand- and tissue-biased signaling of CCR7 and summarize what is known about
bias at other chemokine receptors. CCR7 is expressed by a subset of T-cells and
by mature dendritic cells (DCs). Together with its two endogenous ligands CCL19
and CCL21, of which the carboxy terminal tail of CCL21 displays an
extraordinarily strong glycosaminoglycan (GAG) binding, CCR7 plays a central role
in coordinating the meeting between mature antigen presenting DCs and naive T
cells which normally takes place in the lymph nodes (LNs). This process is a
prerequisite for the initiation of an antigen-specific T-cell mediated immune
response. Thus CCR7 and its ligands are key players in initiating cell-based
immune responses. CCL19 and CCL21 display differential interaction- and docking
modes for CCR7 leading to stabilization of different CCR7 conformations and
hereby preferential activation of distinct intracellular signaling pathways (i.e.
ligand bias). In general CCL19 seems to generate a strong temporal signal,
whereas CCL21 generates a weaker, but more persistent signal. Tissue differential
expression of these two ligands, and the generation of a third ligand "tailless
CCL21", through DC specific protease activity (tissue bias), orchestrates DC and
T-cell LN homing and priming, with each ligand serving overlapping, but also
distinct roles.
PMID- 28694054
TI - Pancreatic PYY but not PPY expression is responsive to short-term nutritional
state and the pancreas constitutes the major site of PYY mRNA expression in
chickens.
AB - PP-fold peptides such as peptide YY (PYY) and pancreatic polypeptide (PPY) are
known to play key roles in vertebrate energy homeostasis. Until recently, no gene
sequence was available for avian PYY and therefore a gap in knowledge of
regulation of its expression exists in avian species. Here we further evidence
the mRNA sequence for chicken PYY and show that the pancreas is the major site of
its mRNA expression, with a secondary peak of expression around the distal
jejunum, in contrast to mammals where the large intestine is the major site of
PYY expression. We also demonstrate that pancreatic PYY expression is responsive
to short-term and long-term nutritional state, increasing within hours of
feeding, in contrast to intestinal PYY which does not fluctuate to the same
extent, and pancreatic PPY which appears to be primarily determined by long-term
energy state. Both pancreatic PYY and PPY expression were found to exhibit
ontogeny, being evenly distributed throughout the pancreas in young (2wk) chicks
but having a decreasing splenic to duodenal gradient by adolescence (12wk).
PMID- 28694055
TI - Estrogen-regulated expression of cyp19a1a and cyp19a1b genes in swim-up fry of
Labeo rohita.
AB - P450 aromatase is the terminal enzyme in the steroidogenic pathway and catalyzes
the conversion of androgens to estrogens. The expression of cyp19a1 genes in
brain and gonad of Indian major carp, Labeo rohita swim-up fry was measured by
quantitative real-time polymerase chain-reaction. Results demonstrated that
cyp19a1b and cyp19a1a predominate in brain and gonad respectively. Treatment of
fry with an aromatase inhibitor fadrozole for 6days attenuated brain cyp19a1b
expression, but not cyp19a1a of gonad. Fadrozole also attenuated brain aromatase
activity. Treatment with 17beta-estradiol (E2) for 6days resulted in up
regulation of brain cyp19a1b transcripts in a dose- and time-dependent manner,
but not cyp19a1a. Whole-body concentration of vitellogenin also increased in
response to E2. Altogether, these results indicate L. rohita swim-up fry can be
used to detect environmental estrogens either using vitellogenin induction or
cyp19a1b gene expression.
PMID- 28694056
TI - The involvement of Rhopr-CRF/DH in feeding and reproduction in the blood-gorging
insect Rhodnius prolixus.
AB - Rhodnius prolixus is a blood-gorging insect and a vector for human Chagas
disease. The insect transmits the disease following feeding, when it excretes
urine and feces contaminated with the Trypanosoma cruzi parasite. A corticotropin
releasing factor-like peptide acts as a diuretic hormone in R. prolixus (Rhopr
CRF/DH); however, its distribution throughout the insect's central nervous system
(CNS) and the expression of its receptor in feeding-related tissue as well as the
female reproductive system suggests a multifaceted role for the hormone beyond
that of diuresis. Here we investigate the involvement of Rhopr-CRF/DH in feeding
and reproduction in R. prolixus. Immunohistochemistry of the CNS showed
diminished CRF-like staining in neurosecretory cells (NSCs) of the mesothoracic
ganglionic mass (MTGM) immediately following feeding, and partial restocking of
those same cells two hours later, indicating Rhopr-CRF/DH stores in this regions
are involved in feeding. The results of the temporal qPCR analysis were
consistent with the immunohistochemical findings, showing an increase in Rhopr
CRF/DH transcript expression in the MTGM immediately after feeding, presumably
capturing the restocking of Rhopr-CRF/DH in the lateral NSCs following release of
the peptide during feeding. Elevating haemolymph Rhopr-CRF/DH titres by injection
of Rhopr-CRF/DH prior to feeding resulted in the intake of a significantly
smaller blood meal in 5th instars and adults without an apparent effect on the
rate of short-term diuresis. When adult females were injected with Rhopr-CRF/DH,
they also produced and laid significantly fewer eggs. Finally, in vitro oviduct
contraction assays illustrate that Rhopr-CRF/DH inhibits the amplitude of
contractions of the lateral oviducts, highlighting a potential mechanism via
which the hormone diminishes reproductive capacity. To conclude, the study of the
Rhopr-CRF/DH pathway, its components and mechanisms of action, has implications
for vector control by highlighting targets to alter feeding, diuresis, and
reproduction of this disease vector.
PMID- 28694057
TI - Planned home birth.
AB - With increasing medical advances and the ability to rescue the mother and her
baby, there has been a growth in the number of women who deliver in hospital
facilities. This allows full care to be provided if required [1]. Maternal and
perinatal mortality has fallen accordingly. This improvement in mother and baby
outcomes has produced a conception of maternity safety in the developed world and
a call for the return to home birth. This has concerned the obstetricians and
particularly the paediatricians who feel that this produces unacceptable risk to
the mother and her baby. However, evidence, mostly from Europe but some from the
US, suggests that home birth can be relatively safe in the right circumstances.
This needs a fully integrated comprehensive maternity care network that is
supportive and responsive. The question is whether this should be supported to
help improve the safety of home birth or resisted because home birth in many
situations is inherently unsafe.
PMID- 28694058
TI - The longitudinal relation between self-reported physical activity and
presenteeism.
AB - This study evaluates the longitudinal relation between self-reported physical
activity and health related work limitations (also known as presenteeism) among
employees from a public university system. A retrospective longitudinal study
design was used to examine research aims. Data were from self-reported health
assessments collected from employees at a large University System in Texas during
the 2013-2015 plan years (n=6515).Work limitations were measured using the self
report 8-item work limitations questionnaire. Latent growth curve models were
used to test whether: 1) baseline physical activity was associated with baseline
work limitations; 2) changes in physical activity were related to changes in work
limitations; and 3) baseline physical activity predicted changes in work
limitations. Models were adjusted for demographic and health-related variables.
The final adjusted growth curve model demonstrated excellent fit. Results
revealed baseline physical activity was inversely associated with baseline work
limitations (beta=-0.12, p<0.001). In addition, changes in physical activity were
related to changes in work limitations (beta=-0.33, p=0.02). However, no relation
was found between baseline physical activity and changes in work limitations
(beta=-0.06, p=0.42). Results provide evidence that increasing physical activity
among employees leads to decreases in health-related work limitations. Therefore,
promoting physical activity among employee populations can help prevent and
reduce presenteeism.
PMID- 28694059
TI - Mental health predictors of breastfeeding initiation and continuation among HIV
infected and uninfected women in a South African birth cohort study.
AB - Breastfeeding is a cost-effective, yet underutilized strategy to promote maternal
and infant health in low and middle income countries (LMICs). Breastfeeding
remains challenging for mothers living with HIV in LMICs, yet few studies have
examined mental health predictors of breastfeeding initiation and continuation.
We investigated breastfeeding among mothers by HIV status in South Africa,
evaluating predictors of breastfeeding initiation and continuation to identify
intervention-targets. Breastfeeding patterns were investigated in a subsample of
899 breastfeeding mothers from the Drakenstein Child Health Study; a prospective
birth cohort of 1225 pregnant women, between March 2012 and March 2015 in a peri
urban area. Breastfeeding was assessed at 5 time-points between 6weeks and
24months' infant age. Cox proportional hazard models evaluated breastfeeding
initiation and duration. Logistic regression models with breastfeeding non
initiation as the outcome parameter were performed to determine associations with
maternal sociodemographic, psychosocial factors and gestational outcomes. More
HIV-uninfected mothers initiated breastfeeding (n=685, 97%) than HIV-infected
mothers (n=87, 45%). Median duration of exclusive breastfeeding was short
(2months), but HIV-infected mothers engaged in exclusive breastfeeding for longer
duration than uninfected mothers (3 vs 2months). Despite concerning high rates,
mental disorders were not significant predictors of breastfeeding behaviour.
Employment and HIV diagnosis during pregnancy predicted a lower likelihood of
breastfeeding initiation among HIV-infected mothers, while employment was
associated with earlier breastfeeding-discontinuation in HIV-uninfected mothers.
Findings indicate that future interventions should target sub-populations such as
HIV-infected women because of distinct needs. Workplace interventions appear
particularly key for mothers in our study.
PMID- 28694060
TI - Temporal growth and spatial distribution of the fast food industry and its
relationship with economic development in China - 2005-2012.
AB - The fast food (FF) industry has expanded rapidly in China during the past two
decades, in parallel with an increase in the prevalence of obesity. Using
government-reported longitudinal data from 21 provinces and cities in China, this
study examined the growth over time and the spatial distribution patterns of the
FF industry as well as the key social economic factors involved. We visualized
the temporal and geographic distributions of FF industry development and
conducted cross-sectional and longitudinal spatial analysis to assess
associations between macroeconomic conditions, population dynamics, and the
growth and distributional changes of the industry. It grew faster in the
southeast coastal (more economically developed) areas since 2005 than in other
regions. The industry was: 1) highly correlated with Gross Domestic Product; 2)
highly correlated with per capita disposable income for urban residents; 3)
moderately correlated with urban population; and 4) not correlated with an
increase of population size. The mean center of the FF industry shifted westward
as the mean center of the GDP moved in the same direction, while the mean center
of the population shifted eastward. The results suggest that the rapid FF
industry expansion in China was closely associated with economic growth and that
improving the food environment should be a major component in local economic
development planning.
PMID- 28694061
TI - Is the link between movement and mental health a two-way street? Prospective
associations between physical activity, sedentary behaviour and depressive
symptoms among women living in socioeconomically disadvantaged neighbourhoods.
AB - This study aimed to investigate the bi-directional relationship between different
domains of physical activity (PA), sedentary behaviour (SB) and depressive
symptoms among women living in socioeconomically disadvantaged neighbourhoods in
Victoria, Australia. Women (n=1033), aged 18-46years at Wave 1 (2007/08),
completed self-report measures of PA (leisure-time, transport, occupational,
domestic), SB (TV viewing, computer use, overall sitting time) and depressive
symptoms (CES-D 10) at each study time-point (Wave 2: 2010/11, Wave 3: 2012/13).
Separate linear mixed models were fitted to examine if change in depressive
symptoms differed dependent on each of the baseline PA or SB measures. Similarly,
baseline depressive symptoms were used as a predictor of change in PA and SB. In
secondary analyses, associations between baseline PA or SB and odds of becoming
'at risk' of depression among those not 'at risk' at baseline were examined using
logistic regression. There was no evidence that change in depressive symptoms
differed depending on PA or SB at baseline. In general, there was also no
evidence that change in PA or SB differed depending on baseline depressive
symptoms. One exception was change in leisure-time PA, which declined more among
those with heightened depressive symptoms at baseline (Interaction: beta=-0.003,
95% CI=-0.007, -0.0003). Transport-related PA (adjusted OR=1.06, 95% CI=1.013,
1.101) and domestic PA (adjusted OR=1.02, 95% CI=1.003, 1.040) were associated
with greater odds of becoming at risk of depression at wave 3. There was limited
evidence of a bi-directional relationship between PA, SB and depressive symptoms
in women living in socioeconomically disadvantaged neighbourhoods.
PMID- 28694062
TI - Trends in smoking and obesity among US adults before, during, and after the great
recession and Affordable Care Act roll-out.
AB - This study examined trends in smoking and overweight/obesity rates among United
States (US) adults ages 40years and older by race and socio-economic status (SES)
across three study periods; pre-recession (2003-2005), recession (2007-2009), and
post-recession/Affordable Care Act (2010-2012). Data was obtained from the
Behavioral Risk Factor Surveillance System (BRFSS), and multivariable regression
analysis was used to examine changes in overweight/obesity, smoking, physical
activity and smoking cessation rates over the study periods. There were 2,805,957
adults included in the analysis; 65.5% of the study population was
overweight/obese, and 33.3% were current smokers. Smoking prevalence increased
marginally among those with lower SES (income<$10,000) from pre-recession (52.5%)
to post-recession (52.9%), but declined in other socio-demographic groups. The
odds of overweight/obesity increased in the post-recession (OR: 1.22, 95% CI:
1.21-1.23) and recession (OR: 1.11, 95% CI: 1.11-1.12) periods compared with pre
recession, but odds of smoking overall decreased in the post-recession (OR: 0.93,
95% CI: 0.92-0.94) and recession (OR: 0.95, 95% CI: 0.94-0.97) periods.
Overweight/obesity increased over the study periods, regardless of race, SES or
healthcare access, while smoking rates showed significant declines post-recession
compared with pre-recession, except in low SES groups. These findings suggest
that strategies focused on reducing overweight/obesity and increasing access to
smoking cessation services, especially among low-income adults, are needed.
Prospective studies are needed to better evaluate the influence of the economic
recession and Affordable Care Act on behavioral risk factors.
PMID- 28694063
TI - Crowdsourced data collection for public health: A comparison with nationally
representative, population tobacco use data.
AB - INTRODUCTION: Internet-based crowdsourcing is increasingly used for social and
behavioral research in public health, however the potential generalizability of
crowdsourced data remains unclear. This study assessed the population
representativeness of Internet-based crowdsourced data. METHODS: A total of 3999
U.S. young adults ages 18 to 30years were recruited in 2016 through Internet
based crowdsourcing to complete measures taken from the 2012-2013 National Adult
Tobacco Survey (NATS). Post-hoc sampling weights were created using procedures
similar to the NATS. Weighted analyses were conducted in 2016 to compare
crowdsourced and publicly-available 2012-2013 NATS data on demographics, tobacco
use, and measures of tobacco perceptions and product warning label exposure.
RESULTS: Those in the crowdsourced sample were less likely to report an annual
household income of $50,000 or greater, and e-cigarette, waterpipe, and cigar use
were more prevalent in the crowdsourced sample. High proportions of both samples
indicated cigarette smoking is very harmful and very addictive. Comparable
proportions of non-smokers and smokers reported cigarette warning label exposure,
however the likelihood of reporting that smoking is very harmful by frequency of
warning label exposure was lower among smokers in the crowdsourced sample.
CONCLUSIONS: Our findings indicate that crowdsourced samples may differ
demographically and may not produce generalizable estimates of tobacco use
prevalence relative to population data after post-hoc sample weighting. However,
correlational analyses in crowdsourced samples may reasonably approximate
population data. Future studies can build from this work by testing additional
methodological strategies to improve crowdsourced sampling strategies.
PMID- 28694064
TI - RNA fluorescence in situ hybridization for high-content screening.
AB - Single molecule RNA imaging using fluorescent in situ hybridization (FISH) can
provide quantitative information on mRNA abundance and localization in a single
cell. There is now a growing interest in screening for modifiers of RNA abundance
and/or localization. For instance, microsatellite expansion within RNA can lead
to toxic gain-of-function via mislocalization of these transcripts into RNA
aggregate and sequestration of RNA-binding proteins. Screening for inhibitors of
these RNA aggregate can be performed by high-throughput RNA FISH. Here we
describe detailed methods to perform single molecule RNA FISH in multiwell plates
for high-content screening (HCS) microscopy. We include protocols adapted for HCS
with either standard RNA FISH with fluorescent oligonucleotide probes or the
recent single molecule inexpensive FISH (smiFISH). Recommendations for success in
HCS microscopy with high magnification objectives are discussed.
PMID- 28694065
TI - The power of bioluminescence imaging in understanding host-pathogen interactions.
AB - Infectious diseases are one of the leading causes of death worldwide. Modelling
and understanding human infection is imperative to developing treatments to
reduce the global burden of infectious disease. Bioluminescence imaging is a
highly sensitive, non-invasive technique based on the detection of light,
produced by luciferase-catalysed reactions. In the study of infectious disease,
bioluminescence imaging is a well-established technique; it can be used to
detect, localize and quantify specific immune cells, pathogens or immunological
processes. This enables longitudinal studies in which the spectrum of the disease
process and its response to therapies can be monitored. Light producing
transgenic rodents are emerging as key tools in the study of host response to
infection. Here, we review the strategies for identifying biological processes in
vivo, including the technology of bioluminescence imaging and illustrate how this
technique is shedding light on the host-pathogen relationship.
PMID- 28694066
TI - Disease gene classification with metagraph representations.
AB - Protein-protein interaction (PPI) networks play an important role in studying the
functional roles of proteins, including their association with diseases. However,
protein interaction networks are not sufficient without the support of additional
biological knowledge for proteins such as their molecular functions and
biological processes. To complement and enrich PPI networks, we propose to
exploit biological properties of individual proteins. More specifically, we
integrate keywords describing protein properties into the PPI network, and
construct a novel PPI-Keywords (PPIK) network consisting of both proteins and
keywords as two different types of nodes. As disease proteins tend to have a
similar topological characteristics on the PPIK network, we further propose to
represent proteins with metagraphs. Different from a traditional network motif or
subgraph, a metagraph can capture a particular topological arrangement involving
the interactions/associations between both proteins and keywords. Based on the
novel metagraph representations for proteins, we further build classifiers for
disease protein classification through supervised learning. Our experiments on
three different PPI databases demonstrate that the proposed method consistently
improves disease protein prediction across various classifiers, by 15.3% in AUC
on average. It outperforms the baselines including the diffusion-based methods
(e.g., RWR) and the module-based methods by 13.8-32.9% for overall disease
protein prediction. For predicting breast cancer genes, it outperforms RWR,
PRINCE and the module-based baselines by 6.6-14.2%. Finally, our predictions also
turn out to have better correlations with literature findings from PubMed.
PMID- 28694067
TI - Pharmacological analysis of the inhibition produced by moxonidine and agmatine on
the vasodepressor sensory CGRPergic outflow in pithed rats.
AB - Calcitonin gene-related peptide (CGRP) plays a role in several
(patho)physiological functions, and modulation of its release is considered a
therapeutic target. In this respect, electrical spinal (T9--T12) stimulation of
the perivascular sensory outflow in pithed rats produces vasodepressor responses
mediated by CGRP release. This study investigated the role of imidazoline I1 and
I2 receptors in the inhibition by moxonidine and agmatine of these vasodepressor
responses. Male Wistar pithed rats (pretreated i.v. with 25mg/kg gallamine and
2mg/kg?min hexamethonium) received i.v. continuous infusions of methoxamine
(20MUg/kg?min) followed by physiological saline (0.02ml/min), moxonidine (1, 3,
10 or 30MUg/kg?min) or agmatine (1000 or 3000MUg/kg?min). Under these conditions,
electrical stimulation (0.56-5.6Hz; 50V; 2ms) of the spinal cord (T9-T12)
produced frequency-dependent vasodepressor responses which were: (i) unchanged
during saline infusion; and (ii) inhibited during the above infusions of
moxonidine or agmatine. Moreover, using i.v. administrations, the inhibition by
3MUg/kg?min moxonidine or 3000MUg/kg?min agmatine (which failed to inhibit the
vasodepressor responses by alpha-CGRP; 0.1-1ug/kg) was: (i) unaltered after
saline (1ml/kg), rauwolscine (300MUg/kg; alpha2-adrenoceptor antagonist) or BU224
(300MUg/kg; imidazoline I2 receptor antagonist); and (ii) reversed after AGN
192403 (3000MUg/kg; imidazoline I1 receptor antagonist). This reversion was
relatively more pronounced after AGN 192403 plus rauwolscine. These blocking
doses of antagonists lacked any effects on the electrically-induced vasodepressor
responses. Therefore, the inhibition of the vasodepressor sensory CGRPergic
outflow by moxonidine and agmatine is mainly mediated by prejunctional
imidazoline I1 receptors on perivascular sensory nerves.
PMID- 28694068
TI - JKB-122 is effective, alone or in combination with prednisolone in Con A-induced
hepatitis.
AB - Con A-induced hepatitis in mice is an established model of autoimmune hepatitis
(AIH). JKB-122, a toll-like receptor 4 (TLR4) antagonist, was tested for
hepatotprotectant activity. Within several hours of Con A challenge (15mg/kg iv),
increased production of proinflammatory cytokines with inflammatory infiltrate
occurred in the liver. The severity of tissue necrosis and the amount of
circulating liver enzymes peak at 24h post Con A challenge. JKB-122 was given 24
and 16h before, then concurrently, and 4 and 8h (* 5 doses) after challenge with
Con A. Serum and liver were harvested at 3, 9 and 24h post Con A challenge. JKB
122 at 20 and 50mg/kg po prevented the increase of serum liver enzymes by 47% and
95% respectively vs vehicle control 24h post Con A. JKB-122 significantly
inhibited Con A-induced pathological lesions in the liver and the amount of IFN
gamma IL-1beta, IL-4, IL-5, IL-6, IL-17A and TNF-alpha starting as early as 3h
post Con A. Moreover, JKB-122 given concurrently (* 3 doses) with Con A showed
similar effect. Finally, JKB-122 enhanced the therapeutic effects of submaximal
dose of prednisolone with improved lesion score. It is concluded that JKB-122 at
20 and 50mg/kg po caused dose-dependent inhibition of elevated liver enzymes in
Con A-induced hepatitis in mice, indicating hepatoprotectant activity. The
results suggest that JKB-122 as monotherapy or in combination with prednisolone
may offer a viable approach to the treatment of AIH.
PMID- 28694070
TI - The Roles of Actin-Binding Domains 1 and 2 in the Calcium-Dependent Regulation of
Actin Filament Bundling by Human Plastins.
AB - The actin cytoskeleton is a complex network controlled by a vast array of
intricately regulated actin-binding proteins. Human plastins (PLS1, PLS2, and
PLS3) are evolutionary conserved proteins that non-covalently crosslink actin
filaments into tight bundles. Through stabilization of such bundles, plastins
contribute, in an isoform-specific manner, to the formation of kidney and
intestinal microvilli, inner ear stereocilia, immune synapses, endocytic patches,
adhesion contacts, and invadosomes of immune and cancer cells. All plastins
comprise an N-terminal Ca2+-binding regulatory headpiece domain followed by two
actin-binding domains (ABD1 and ABD2). Actin bundling occurs due to simultaneous
binding of both ABDs to separate actin filaments. Bundling is negatively
regulated by Ca2+, but the mechanism of this inhibition remains unknown. In this
study, we found that the bundling abilities of PLS1 and PLS2 were similarly
sensitive to Ca2+ (pCa50 ~6.4), whereas PLS3 was less sensitive (pCa50 ~5.9). At
the same time, all three isoforms bound to F-actin in a Ca2+-independent manner,
suggesting that binding of only one of the ABDs is inhibited by Ca2+. Using
limited proteolysis and mass spectrometry, we found that in the presence of Ca2+
the EF-hands of human plastins bound to an immediately adjacent sequence
homologous to canonical calmodulin-binding peptides. Furthermore, our data from
differential centrifugation, Forster resonance energy transfer, native
electrophoresis, and chemical crosslinking suggest that Ca2+ does not affect ABD1
but inhibits the ability of ABD2 to interact with actin. A structural mechanism
of signal transmission from Ca2+ to ABD2 through EF-hands remains to be
established.
PMID- 28694069
TI - Engineering Aglycosylated IgG Variants with Wild-Type or Improved Binding
Affinity to Human Fc Gamma RIIA and Fc Gamma RIIIAs.
AB - The binding of human IgG1 to human Fc gamma receptors (hFcgammaRs) is highly
sensitive to the presence of a single N-linked glycosylation site at asparagine
297 of the Fc, with deglycosylation resulting in a complete loss of hFcgammaR
binding. Previously, we demonstrated that aglycosylated human IgG1 Fc variants
can engage the human FcgammaRII class of the low-affinity hFcgammaRs,
demonstrating that N-linked glycosylation of the Fc is not a strict requirement
for hFcgammaR engagement. In the present study, we demonstrate that aglycosylated
IgG variants can be engineered to productively engage with FcgammaRIIIA, as well
as the human Fc gamma RII subset. We also assess the biophysical properties and
serum half-life of the aglycosylated IgG variants to measure stability.
Aglycosylated constructs N297D/S298T (DTT)-K326I/A327Y/L328G (IYG) and
N297D/S298A-IYG optimally drove tumor cell phagocytosis. A mathematical model of
phagocytosis suggests that hFcgammaRI and hFcgammaRIIIA dimers were the main
drivers of phagocytosis. In vivo tumor control of B16F10 lung metastases further
confirmed the variant DTT-IYG to be the best at restoring wild-type-like
properties in prevention of lung metastases. While deuterium incorporation was
similar across most of the protein, several peptides within the CH2 domain of DTT
IYG showed differential deuterium uptake in the peptide region of the FG loop as
compared to the aglycosylated N297Q. Thus, in this study, we have found an
aglycosylated variant that may effectively substitute for wild-type Fc. These
aglycosylated variants have the potential to allow therapeutic antibodies to be
produced in virtually any expression system and still maintain effector function.
PMID- 28694071
TI - First clinical and genetic description of a family diagnosed with late-onset
Pompe disease from Costa Rica.
AB - Glycogen storage disease type II, also known as Pompe disease, is an autosomal
recessive disorder caused by deficiency of enzymatic activity of acid alpha
glucosidase. The wide phenotypical variation of this disease relates to the
amount of residual enzymatic activity depending on the combination of mutations
on each allele. We confirmed Pompe disease in a patient that presented with
progressive weakness, recurrent episodes of respiratory failure associated with
pneumonia, a predominantly demyelinating mixed sensorimotor polyneuropathy and
paraspinal complex repetitive discharges. Genetic analysis of the GAA gene from
this patient revealed two pathogenic compound heterozygous mutations: c.-32-13T>G
(rs386834236, intronic), c.2560C>T (rs121907943, p.Arg854Ter); and one variant of
unknown significance: c.1551+42G>A (rs115427918, intronic). We found expected
mutations in two siblings and two nieces. Genetic variants reported in this
family reflect on the European and African ancestry that we carry in our Costa
Rican population.
PMID- 28694072
TI - Acquired equine polyneuropathy of Nordic horses: A conspicuous inclusion body
schwannopathy.
AB - Acquired equine polyneuropathy (AEP), formerly also known as Scandinavian
knuckling syndrome, is one of the most prevalent polyneuropathies in equids in
Norway and Sweden, with more than 400 cases registered since first observations
in 1995. Despite geographical clustering and an association to forage feeding,
its aetiology remains unknown. Clinically AEP is characterized by knuckling due
to dysfunction of metatarsophalangeal extensor muscles. This neuropathological
study aimed to gain further insights in the pathobiology of AEP and its
underlying aetiopathogenesis. We thereby confirmed that all affected horses
suffered from similar large fibre neuropathy, exhibiting conspicuous Schwann cell
inclusions in most samples, suggestive of a primary disruption of Schwann cell
metabolism leading to inclusion body schwannopathy with secondary inflammatory
changes. The degree of nerve pathology was not predictive of clinical outcome.
PMID- 28694073
TI - Gluteus maximus hypertrophy: A diagnostic clue in four and a half LIM domain 1
mutated reducing body myopathy.
PMID- 28694074
TI - Memory B cell resurgence requires repeated rituximab in myasthenia gravis.
AB - The immunologic effects of rituximab (RTX) in myasthenia gravis (MG) remain to be
explored. We aimed to clarify immunologic reactions and their association with
response to RTX in MG. Regulatory T cell and B cell profiles of MG patients were
monitored. Two patients presenting with generalized MG with anti-acetylcholine
receptor antibodies were treated with RTX. The treatment led to sustained
clinical improvement, discontinuation of intravenous immunoglobulin or plasma
exchange, and reduction of prednisolone and other drugs. One patient was in
remission for more than one year, whereas the other patient exhibited
deterioration of symptoms within one year. Disease activity was associated with
the repopulation of IgD-CD27- and IgD-CD27+ memory B cells. Clinicians should be
aware of the possibility that MG ranges in the duration of B cell depletion and
additional RTX should be prescribed upon resurgence of memory B cells.
PMID- 28694075
TI - Double-seropositive myasthenia gravis with acetylcholine receptor and low-density
lipoprotein receptor-related protein 4 antibodies associated with invasive
thymoma.
AB - We describe two cases of myasthenia gravis (MG) with double seropositivity for
acetylcholine receptor (AChR) and low-density lipoprotein receptor-related
protein 4 (LRP4) antibodies (AChR/LRP4-MG) with invasive thymoma. Both cases
showed myasthenic weakness, which was restricted to the ocular muscles for >5
months from onset, and then unprovoked severe clinical deterioration supervened
with predominant bulbar symptoms. The patients responded adequately to
therapeutic intervention. Serum AChR antibody levels at post-intervention were
markedly decreased, whereas LRP4 antibodies were almost unchanged in case 1 and
slightly decreased in case 2. Although our results suggest that patients with
AChR/LRP4-MG are likely to present with more severe symptoms than those with LRP4
MG, none of the previously reported cases had thymomas. Coexistence of
autoantibodies may reflect breakdown of self-tolerance caused by invasive
thymomas. The main cause affecting symptoms of MG in our cases was probably AChR
antibodies, and anti-LRP4 antibodies might have been an exacerbating factor.
PMID- 28694076
TI - Traumatic avulsion of the flexor digitorum profundus tendon. Jersey finger, a 29
cases report.
AB - Traumatic avulsion of flexor digitorum profundus (jersey finger) is an uncommon
injury. Our study aimed to describe functional outcomes of jersey fingers after
surgical treatment. From January 2004 to 2014, we performed surgery on 32
patients who had jersey finger. Twenty-six of these patients were male and 6 were
female with a mean age of 37.2years (range 16-68). Of the 32 cases, 11 were
sports injuries, 16 presented on the ring finger and 13 on the little finger.
Using the Leddy and Packer and Smith classifications, 16 of the injuries were
type I, 4 were type II, 5 were type III, 7 were type IV. The mean time between
injury and surgery was 6.8days (range: 0-32). The surgical techniques used were
anchor, pull-out, or an association of both these techniques. Prior to the
patient discharge, functional outcomes were evaluated. Twenty-nine patients were
evaluated in total and three patients were lost. Of the 29, the average time
between surgery and discharge was 36.6months ranging from 4.5 to 118months.
According to the Buck-Gramcko classification, six patients had an excellent
result, six had a good result, seven had a satisfactory result and ten a poor
result. The mean Quick DASH score immediately to prior discharge was 5.66 (range:
0-56.82). Twelve complications were reported on nine patients. No infections were
reported. Rapid diagnosis and rapid surgical treatment led to restoration of full
range motion.
PMID- 28694078
TI - Robotic versus Open Level I-II Inferior Vena Cava Thrombectomy: A Matched Group
Comparative Analysis.
AB - PURPOSE: We compared treatment outcomes of robotic vs open inferior vena cava
thrombectomy for renal tumors with level I-II inferior vena cava tumor thrombus.
MATERIALS AND METHODS: We retrospectively reviewed the medical records of
patients who underwent robotic or open inferior vena cava thrombectomy between
2006 and 2016. To reduce the inherent biases of a nonrandomized study the robotic
and open groups were matched 1:1 based on key variables. Perioperative data and
oncologic outcomes were reviewed. Progression-free and overall survival was
analyzed using Kaplan-Meier survival curves and compared between groups using the
log rank test. RESULTS: A total of 31 and 37 patients underwent robotic and open
inferior vena cava thrombectomy, respectively. After matching there were no
significant differences in baseline characteristics between the groups. Of the
matched cohorts the robotic cohort had significantly shorter median operative
time (150 vs 230 minutes, p <0.001), lower median estimated blood loss (250 vs
1,000 ml, p <0.001), a lower rate of blood transfusion (6.5% vs 54.8%, p <0.001),
a lower median transfusion requirement (420 vs 790 ml, p = 0.012) and a shorter
median postoperative hospital stay (5 vs 9 days, p <0.001). The postoperative
complication rate was lower in the robotic group than in the open group (9.7% vs
29.0%, p = 0.070). However, there were no significant differences in oncologic
outcomes between the groups. CONCLUSIONS: Robotic inferior vena cava thrombectomy
can achieve more favorable perioperative results and similar oncologic outcomes
compared with open inferior vena cava thrombectomy. Prospective studies with a
larger sample size and longer followup are needed to validate our findings.
PMID- 28694077
TI - Molecular adaptation to high pressure in cytochrome P450 1A and aryl hydrocarbon
receptor systems of the deep-sea fish Coryphaenoides armatus.
AB - Limited knowledge of the molecular evolution of deep-sea fish proteomes so far
suggests that a few widespread residue substitutions in cytosolic proteins
binding hydrophilic ligands contribute to resistance to the effects of high
hydrostatic pressure (HP). Structure-function studies with additional protein
systems, including membrane bound proteins, are essential to provide a more
general picture of adaptation in these extremophiles. We explored molecular
features of HP adaptation in proteins binding hydrophobic ligands, either in
lipid bilayers (cytochrome P450 1A - CYP1A) or in the cytosol (the aryl
hydrocarbon receptor - AHR), and their partners P450 oxidoreductase (POR) and AHR
nuclear translocator (ARNT), respectively. Cloning studies identified the full
length coding sequence of AHR, CYP1A and POR, and a partial sequence of ARNT from
Coryphaenoides armatus, an abyssal gadiform fish thriving down to 5000m depth.
Inferred protein sequences were aligned with many non-deep-sea homologs to
identify unique amino acid substitutions of possible relevance in HP adaptation.
Positionally unique substitutions of various physicochemical properties were
found in all four proteins, usually at sites of strong-to-absolute residue
conservation. Some were in domains deemed important for protein-protein
interaction or ligand binding. In addition, some involved removal or addition of
beta-branched residues; local modifications of beta-branched residue patterns
could be important to HP adaptation. In silico predictions further suggested that
some unique substitutions might substantially modulate the flexibility of the
polypeptide segment in which they are found. Repetitive motifs unique to the
abyssal fish AHR were predicted to be rich in glycosylation sites, suggesting
that post-translational changes could be involved in adaptation as well.
Recombinant CYP1A and AHR showed functional properties (spectral characteristics,
catalytic activity and ligand binding) that demonstrate proper folding at 1atm,
indicating that they could be used as deep-sea fish protein models to further
evaluate protein function under pressure. This article is part of a Special Issue
entitled: Cytochrome P450 biodiversity and biotechnology, edited by Erika
Plettner, Gianfranco Gilardi, Luet Wong, Vlada Urlacher, Jared Goldstone".
PMID- 28694079
TI - Distal Ureteral Diameter Ratio is Predictive of Breakthrough Febrile Urinary
Tract Infection.
AB - PURPOSE: Distal ureteral diameter ratio is an objective measure that is
prognostic of spontaneous resolution of vesicoureteral reflux. Along with
likelihood of resolution, improved identification of children at risk for
recurrent febrile urinary tract infections may impact management decisions. We
evaluated the usefulness of ureteral diameter ratio as a predictive factor for
breakthrough febrile urinary tract infections. MATERIALS AND METHODS: Children
with primary vesicoureteral reflux and detailed voiding cystourethrogram were
identified. Ureteral diameter ratio was computed by measuring largest ureteral
diameter within the pelvis and dividing by the distance between L1 and L3
vertebral bodies. Demographics, vesicoureteral reflux grade, laterality,
presence/absence of bladder-bowel dysfunction, and ureteral diameter ratio were
tested in univariate and multivariable analyses. Primary outcome was breakthrough
febrile urinary tract infections. RESULTS: We analyzed 112 girls and 28 boys with
a mean +/- SD age of 2.5 +/- 2.3 years at diagnosis. Vesicoureteral reflux was
grade 1 to 2 in 64 patients (45.7%), grade 3 in 50 (35.7%), grade 4 in 16 (11.4%)
and grade 5 in 10 (7.2%). Mean +/- SD followup was 3.2 +/- 2.7 years. A total of
40 children (28.6%) experienced breakthrough febrile urinary tract infections.
Ureteral diameter ratio was significantly greater in children with (0.36) vs
without (0.25) breakthrough febrile infections (p = 0.004). Controlling for
vesicoureteral reflux grade, every 0.1 U increase in ureteral diameter ratio
resulted in 1.7 times increased odds of breakthrough infection (95% CI 1.24 to
2.26, p <0.0001). CONCLUSIONS: Children with increased distal ureteral diameter
ratio are at greater risk for breakthrough febrile urinary tract infections
independent of reflux grade. Ureteral diameter ratio provides valuable prognostic
information about risk of recurrent pyelonephritis and may assist with clinical
decision-making.
PMID- 28694080
TI - Analysis of genetic association using hierarchical clustering and cluster
validation indices.
AB - It is usually assumed that co-expressed genes suggest co-regulation in the
underlying regulatory network. Determining sets of co-expressed genes is an
important task, based on some criteria of similarity. This task is usually
performed by clustering algorithms, where the genes are clustered into meaningful
groups based on their expression values in a set of experiment. In this work, we
propose a method to find sets of co-expressed genes, based on cluster validation
indices as a measure of similarity for individual gene groups, and a combination
of variants of hierarchical clustering to generate the candidate groups. We
evaluated its ability to retrieve significant sets on simulated correlated and
real genomics data, where the performance is measured based on its detection
ability of co-regulated sets against a full search. Additionally, we analyzed the
quality of the best ranked groups using an online bioinformatics tool that
provides network information for the selected genes.
PMID- 28694081
TI - Deletion of 12/15-lipoxygenase accelerates the development of aging-associated
and instability-induced osteoarthritis.
AB - OBJECTIVE: 12/15-Lipoxygenase (12/15-LOX) catalyzes the generation of various
anti-inflammatory lipid mediators, and has been implicated in several
inflammatory and degenerative diseases. However, there is currently no evidence
that 12/15-LOX has a role in osteoarthritis (OA). The aim of this study was to
investigate the role of 12/15-LOX in the pathogenesis of OA. METHODS: The
development of aging-associated and destabilization of the medial meniscus (DMM)
induced OA were compared in 12/15-LOX-deficient (12/15-LOX-/-) and wild-type (WT)
mice. The extent of cartilage damage was evaluated by histology. The expression
of OA markers was evaluated by immunohistochemistry and RT-PCR. Cartilage
explants were stimulated with IL-1alpha in the absence or presence of the 12/15
LOX metabolites, 15-hydroxyeicosatetraenoic acids (15-HETE), 13
hydroxyoctadecadienoic acid (13-HODE) or lipoxin A4 (LXA4), and the levels of
matrix metalloproteinases-13 (MMP-13), Nitric oxide (NO) and prostaglandin E2
(PGE2) were determined. The effect of LXA4 on the progression of OA was evaluated
in wild type (WT) mice. RESULTS: The expression of 12/15-LOX in cartilage
increased during the progression of DMM-induced OA and with aging in WT mice.
Cartilage degeneration was more severe in 12/15-LOX-/- mice compared to WT mice
in both models of OA, and this was associated with increased expression of MMP
13, a disintegrin and metalloproteinase with thrombospondin motifs, aggrecanases
(ADAMTS5), inducible NO synthases (iNOS), and mPGES-1. Treatment of cartilage
explants with 12/15-LOX metabolites, suppressed IL-1alpha-induced production of
MMP-13, NO and PGE2, with LXA4 being the most potent. Intra-peritoneal injection
of LXA4 reduced the severity of DMM-induced cartilage degradation. CONCLUSIONS:
These data suggest an important role of 12/15-LOX in the pathogenesis of OA. They
also suggest that activation of this pathway may provide a novel strategy for
prevention and treatment of OA.
PMID- 28694082
TI - Interest of metabonomic approach in environmental nephrotoxicants: Application to
aristolochic acid exposure.
PMID- 28694083
TI - Impact of surface functionalization on the uptake mechanism and toxicity effects
of silver nanoparticles in HepG2 cells.
AB - Safe and successful bioapplications of metallic nanoparticles depend on their
physicochemical characteristics, in particular their surface properties. This
study aimed to investigate how different surface functionalization of silver
nanoparticles (AgNP) affect their interaction with mammalian liver cells with
regard to cytotoxicity, genotoxicity and mechanism of cellular uptake.
Differentially coated AgNP were prepared by surface functionalization using
sodium bis(2-ethylhexyl)-sulfosuccinate (AOTAgNP), cetyltrimethylammonium bromide
(CTABAgNP), poly(vinylpyrrolidone) (PVPAgNP), poly-l-lysine (PLLAgNP), and bovine
serum albumin (BSAAgNP). Data showed varying toxic potential of differentially
coated AgNP. All AgNP types demonstrated concentration dependent effects on
cytotoxicity and genotoxicity in HepG2 cells. Cytotoxic potential of
differentially coated AgNP followed the order of BSAAgNP > PLLAgNP > CTABAgNP >
AOTAgNP > PVPAgNP. Exposure of HepG2 cells to non-cytotoxic concentrations (up to
10 mg Ag/L) of AgNP for 24 h induced primary DNA damage as evaluated by alkaline
comet assay. The highest increase in both comet tail length and tail intensity
was produced by PLLAgNP followed by AOTAgNP, while CTABAgNP appeared to be least
damaging. The main uptake mechanisms of AgNP were macropinocytosis and clathrin
mediated endocytosis. The study findings contribute to the criteria that should
be considered in evaluating the biocompatibility and safety of novel
nanomaterials.
PMID- 28694084
TI - Olanzapine Reduces Chemotherapy-induced Nausea and Vomiting Compared With
Aprepitant in Myeloma Patients Receiving High-dose Melphalan Before Stem Cell
Transplantation: A Retrospective Study.
AB - INTRODUCTION: Acute and delayed chemotherapy-induced nausea and vomiting (CINV)
occurs in most patients who receive high-dose melphalan and significantly affects
patients' quality of life during autologous stem cell transplantation. Faced with
unsatisfactory results using an aprepitant-based regimen, an olanzapine-based
regimen was initiated, with the hope of improving the incidence of acute and
delayed CINV. A retrospective study was conducted to compare the effectiveness of
olanzapine- versus aprepitant-based regimens for CINV prevention in adult
hematopoietic stem cell recipients who received high-dose melphalan. PATIENTS AND
METHODS: We compared olanzapine (n = 43) to aprepitant (n = 54) and fosaprepitant
(n = 20). Olanzapine was given orally at 5 mg twice daily for 5 days, aprepitant
was given at 125 mg on day -1 and 80 mg on days 0 and 1, and fosaprepitant was
given at 150 mg on day -1. The dose of 2 concomitant drugs (dexamethasone and 5
hydroxytryptamine type 3 receptor antagonist) was similar in the 2 groups. Nausea
prevention was the primary endpoint. A complete response using a composite index
of no emesis and no use of rescue medications was the secondary endpoint.
RESULTS: The results showed that olanzapine significantly reduced the number of
patients who experienced acute (P < .0001) or delayed (P < .004) nausea and
significantly reduced the use of rescue medications for acute-onset (P < .0046)
and delayed-onset (P < .0001) CINV compared with aprepitant. CONCLUSION: Compared
with fosaprepitant, olanzapine reduced the number of patients with acute (P <
.0318) and delayed (P < .1519) nausea and reduced the need for rescue medications
for acute-onset (P < .0643) and delayed-onset (P < .0024) CINV.
PMID- 28694085
TI - Baseline Characteristics Predicting Very Good Outcome of Allogeneic Hematopoietic
Cell Transplantation in Young Patients With High Cytogenetic Risk Chronic
Lymphocytic Leukemia - A Retrospective Analysis From the Chronic Malignancies
Working Party of the EBMT.
AB - BACKGROUND: Patients with genetically high-risk relapsed/refractory chronic
lymphocytic leukemia have shorter median progression-free survival (PFS) with
kinase- and BCL2-inhibitors (KI, BCL2i). Allogeneic hematopoietic stem cell
transplantation (alloHCT) may result in sustained PFS, especially in younger
patients because of its age-dependent non-relapse mortality (NRM) risk, but
outcome data are lacking for this population. PATIENTS AND METHODS: Risk factors
for 2-year NRM and 8-year PFS were identified in patients < 50 years in an
updated European Society for Blood and Marrow Transplantation registry cohort (n
= 197; median follow-up, 90.4 months) by Cox regression modeling, and predicted
probabilities of NRM and PFS of 2 reference patients with favorable or
unfavorable characteristics were plotted. RESULTS: Predictors for poor 8-year PFS
were no remission at the time of alloHCT (hazard ratio [HR], 1.7; 95% confidence
interval [CI], 1.1-2.5) and partially human leukocyte antigen (HLA)-mismatched
unrelated donor (HR, 2.8; 95% CI, 1.5-5.2). The latter variable also predicted a
higher risk of 2-year NRM (HR, 4.0; 95% CI, 1.4-11.6) compared with HLA-matched
sibling donors. Predicted 2-year NRM and 8-year PFS of a high cytogenetic risk
(del(17p) and/or del(11q)) patient in remission with a matched related donor were
12% (95% CI, 3%-22%) and 54% (95% CI, 38%-69%), and for an unresponsive patient
with a female partially HLA-matched unrelated donor 37% (95% CI, 12%-62%) and 38%
(95% CI, 13%-63%). CONCLUSION: Low predicted NRM and high 8-year PFS in favorable
transplant high cytogenetic risk patients compares favorably with outcomes with
KI or BCL2i. Taking into account the amount of uncertainty for predicting
survival after alloHCT and after sequential administration of KI and BCL2i,
alloHCT remains a valid option for younger patients with high cytogenetic risk
chronic lymphocytic leukemia with a well-HLA-matched donor.
PMID- 28694086
TI - Association between post-craniotomy Propionibacterium acnes infection and dural
implants: a case-control study.
AB - BACKGROUND: In 2011, 15 deep-seated Propionibacterium acnes infections were
identified in patients following craniotomies in a hospital in the UK. AIM: To
describe the outbreak and report findings from the investigation undertaken in
order to identify the source and risk factors and inform control measures.
METHODS: Data were obtained from hospital clinical records and included patient
and surgical variables. Cases were defined as patients with microbiologically
confirmed deep or organ space surgical site infection (SSI) caused by P. acnes
following craniotomy undertaken in 2011. Four controls per case were randomly
selected from patients who had a craniotomy in 2011 but who did not develop any
SSI. The relationship between infection and putative exposures was examined using
multivariate regression techniques. Infection prevention procedures and the
theatre environment were reviewed to assess compliance with existing standards.
FINDINGS: Fifteen cases and 65 controls were recruited. Odds of infection were
higher for those who had a dural implant inserted during their operation
[adjusted odds ratio (aOR): 14.6; 95% confidence interval (CI): 0.95-infinity]
and for those who had alcohol/Betadine(r)/chlorhexidine mix as a disinfectant
(aOR: 7.9; 95% CI: 0.8-infinity). Environmental investigations suggested that
theatre ventilation systems delivered air exchange rates below the recommended
standard. CONCLUSION: There was a positive association between using dural
implants and P. acnes infection. Infection may have been facilitated by
inefficient use of skin disinfectant and environmental factors. Recommendations
included ongoing surveillance, the use of chlorhexidine skin disinfectant,
ensuring adequate air exchanges and appropriate use of doors in theatre to
minimize air turbulence.
PMID- 28694087
TI - A mathematical model of a recombinant humanized anti-cocaine monoclonal
antibody's effects on cocaine pharmacokinetics in mice.
AB - AIMS: A recombinant humanized anti-cocaine monoclonal antibody (mAb), h2E2, is at
an advanced stage of pre-clinical development as an immunotherapy for cocaine
abuse. It is hypothesized that h2E2 binds to and sequesters cocaine in the blood.
MAIN METHODS: A three-compartment model of the effects of h2E2 on cocaine's
distribution was constructed. The model assumes that h2E2 binds to cocaine and
that the h2E2-cocaine complex does not enter the brain but distributes between
the central and peripheral compartments. Free cocaine is eliminated from both the
central and peripheral compartments, and h2E2 and the h2E2-cocaine complex are
eliminated from the central compartment only. This model was tested against a new
dataset measuring cocaine concentrations in the brain and plasma over 1h in the
presence and absence of h2E2. KEY FINDINGS: The mAb significantly increased
plasma cocaine concentrations with a concomitant significant decrease in brain
concentration. Plasma concentrations declined over the 1-hour sampling period in
both groups. With a set of parameters within reasonable physiological ranges, the
three-compartment model was able to qualitatively and quantitatively simulate the
increased plasma concentration in the presence of the antibody and the decreased
peak brain concentration in the presence of antibody. Importantly, the model
explained the decline in plasma concentrations over time as distribution of the
cocaine-h2E2 complex into a peripheral compartment. SIGNIFICANCE: This model will
facilitate the targeting of ideal mAb PK/PD properties thus accelerating the
identification of lead candidate anti-drug mAbs.
PMID- 28694088
TI - Enhanced expression of tumour suppressor RAR-beta by DSPC nano-formulated lipo
ATRA in the lung of B16F10 cell-implanted C57BL6 mice and in A549 cells.
AB - AIM: All Trans Retinoic acid (ATRA) is an efficient drug for leukemia, but is not
efficient therapy for solid cancers. Hence we have used 1,2-distearoyl-sn-glycero
3-phosphocholine (DSPC) and cholesterol lipo-ATRA to investigate its molecular
therapeutic effect on lung cancer. The objective was to find whether it could
enhance ATRA receptor, RAR-beta expression in lung cells as it was lost in
majority of cancers including lung cancer. MATERIALS AND METHODS: The study was
made in an experimental C57BL/6 mice model developed by tail vein injection of
B16F10 cells and in A549 human lung cancer cells. The RAR-beta protein expression
was studied by Immunohistochemistry/Immunocytochemistry and the mRNA expression
was studied by RT-PCR and qPCR methods. KEY FINDINGS: Both free and lipo-ATRA
treatments showed an enhancement of RAR-beta protein and gene expressions,
indicating its induction on RAR beta. However, lipo-ATRA treatment has shown
significant induction when compared with free ATRA treatment. SIGNIFICANCE: Our
results implies that the DSPC lipo-ATRA treatment might have accumulated more
ATRA in to the target cells which might have resulted in the induction of its
receptor RAR-beta expression in a hypothesis of ligand induced receptor
expression.
PMID- 28694089
TI - The potential protective role of taurine against experimental allergic
inflammation.
AB - AIMS: Taurine has been widely evaluated as a potential therapeutic agent in
chronic inflammatory disorders and various infections. However, the potential
role of taurine in regulating allergic inflammatory responses is currently
unknown. MATERIALS AND METHODS: The present study was designed to evaluate the in
vitro effects of taurine on the levels of thymic stromal lymphopoietin (TSLP) and
other pro-inflammatory cytokines and activation of caspase-1 and nuclear factor
(NF)-kappaB as well as the phosphorylations of c-Jun N-terminal kinase (JNK) and
p38 in phorbol 12-myristate 13-acetate and calcium ionophore A23187 (PMACI)
triggered human mast cell line, HMC-1 cells. Furthermore, we assessed the
therapeutic effects of taurine on ovalbumin (OVA)-induced allergic rhinitis (AR)
animal models. KEY FINDINGS AND SIGNIFICANCE: Here, the obtained results showed
that taurine dose-dependently inhibited the production and mRNA expression of
TSLP and pro-inflammatory cytokines in HMC-1 cells exposed to PMACI. Taurine
attenuated the phosphorylation of JNK and p38 in activated HMC-1 cells. Moreover,
taurine brought a significant inhibition of the activities of NF-kappaB and
caspase-1. In an OVA-induced AR animal model, the increased levels of nose
rubbing, histamine, immunoglobulin E, TSLP, and interleukin IL-1beta were
dramatically reduced by the administration of taurine. In summary, taurine could
serve as potential novel remedy of allergic inflammatory disorders.
PMID- 28694090
TI - Milnacipran affects mouse impulsive, aggressive, and depressive-like behaviors in
a distinct dose-dependent manner.
AB - Serotonin/noradrenaline reuptake inhibitors (SNRIs) are widely used for the
treatment for major depressive disorder, but these drugs induce several side
effects including increased aggression and impulsivity, which are risk factors
for substance abuse, criminal involvement, and suicide. To address this issue,
milnacipran (0, 3, 10, or 30 mg/kg), an SNRI and antidepressant, was
intraperitoneally administered to mice prior to the 3-choice serial reaction time
task, resident-intruder test, and forced swimming test to measure impulsive,
aggressive, and depressive-like behaviors, respectively. A milnacipran dose of 10
mg/kg suppressed all behaviors, which was accompanied by increased dopamine and
serotonin levels in the medial prefrontal cortex (mPFC) but not in the nucleus
accumbens (NAc). Although the most effective dose for depressive-like behavior
was 30 mg/kg, the highest dose increased aggressive behavior and unaffected
impulsive behavior. Increased dopamine levels in the NAc could be responsible for
the effects. In addition, the mice basal impulsivity was negatively correlated
with the latency to the first agonistic behavior. Thus, the optimal dose range of
milnacipran is narrower than previously thought. Finding drugs that increase
serotonin and dopamine levels in the mPFC without affecting dopamine levels in
the NAc is a potential strategy for developing novel antidepressants.
PMID- 28694091
TI - Combined intranasal nerve growth factor and ventricle neural stem cell grafts
prolong survival and improve disease outcome in amyotrophic lateral sclerosis
transgenic mice.
AB - Amyotrophic lateral sclerosis (ALS) is a fatal disease that selectively involves
motor neurons. Neurotrophic factor supplementation and neural stem cell (NSC)
alternative therapy have been used to treat ALS. The two approaches can affect
each other in their pathways of action, and there is a possibility for synergism.
However, to date, there have been no studies demonstrating the effects of
combined therapy in the treatment of ALS. In this study, for the first time, we
adopted a method involving the intranasal administration of nerve growth factor
combined with lateral ventricle NSC transplantation using G93A-SOD1 transgenic
mice as experimental subjects to explore the treatment effect of this combined
therapy in ALS. We discover that the combined therapy increase the quantity of
TrkA receptors, broaden the migration of exogenous NSCs, further promote active
proliferation in neurogenic regions of the brain and enhance the preservation of
motor neurons in the spinal cord. Regarding physical activity, the combined
therapy improved motor functions, further postponed ALS onset and extended the
survival time of the mice.
PMID- 28694092
TI - Deep Infiltrating Endometriosis-Urinary Tract Involvement and Predictive Factors
for Major Surgery.
AB - OBJECTIVE: To evaluate urinary tract involvement by deep infiltrating
endometriosis as well as the surgical treatment and existence of predictive
factors for major urologic surgery. METHODS: We conducted a retrospective
analysis of 656 women submitted to surgery for endometriosis, of which 28
patients underwent minor or major surgery for deep infiltrating endometriosis
involving the urinary tract, with a mean age of 38 +/- 6.9 years (27-50) at
diagnosis. Clinical data, surgeries performed, and complications were analyzed.
Minor surgery was defined by endoscopic surgery or insertion of a percutaneous
nephrostomy catheter, and major surgery included open or laparoscopic procedures.
RESULTS: Endometriomas affected the ureter in 13 (46.4%), the bladder in 11
(39.3%), and both structures in 4 (14.3%) patients. Twelve (42.9%) patients had
decreased renal function, and ureteral involvement was predictive of renal
function loss (P = .034). Minor surgeries were performed in most women with
isolated bladder involvement and in 12 (42.9%) patients with ureteral
infiltration. Patients with ureteric involvement underwent major surgeries more
often (n = 12 vs n = 3; P = .025) and had longer hospitalization (8.2 vs 3.1
days, P = .05). After a mean follow-up of 36.3 (1-102) months, there was no
bladder involvement recurrence. The most common complication was ureteral
stenosis (Clavien-Dindo grade IIIb) in 3 (10.7%) patients. CONCLUSION: Surgery is
highly successful in most cases. Patients with ureteric involvement are more
likely to lose kidney function, undergo major surgery, and have longer
hospitalization.
PMID- 28694095
TI - Drawing a distinction between familiar and unfamiliar voice processing: A review
of neuropsychological, clinical and empirical findings.
AB - Thirty years on from their initial observation that familiar voice recognition is
not the same as unfamiliar voice discrimination (van Lancker and Kreiman, 1987),
the current paper reviews available evidence in support of a distinction between
familiar and unfamiliar voice processing. Here, an extensive review of the
literature is provided, drawing on evidence from four domains of interest: the
neuropsychological study of healthy individuals, neuropsychological investigation
of brain-damaged individuals, the exploration of voice recognition deficits in
less commonly studied clinical conditions, and finally empirical data from
healthy individuals. All evidence is assessed in terms of its contribution to the
question of interest - is familiar voice processing distinct from unfamiliar
voice processing. In this regard, the evidence provides compelling support for
van Lancker and Kreiman's early observation. Two considerations result: First,
the limits of research based on one or other type of voice stimulus are more
clearly appreciated. Second, given the demonstration of a distinction between
unfamiliar and familiar voice processing, a new wave of research is encouraged
which examines the transition involved as a voice is learned.
PMID- 28694094
TI - Intracorneal melatonin delivery using 2-hydroxypropyl-beta-cyclodextrin
ophthalmic solution for granular corneal dystrophy type 2.
AB - Melatonin (MT), an effective antioxidant, has therapeutic implications for
granular corneal dystrophy type 2 (GCD2) treatment. Eye drop formulations
containing cyclodextrins (CDs) were studied with the objective of improving MT
solubility, stability, and ocular absorption, while decreasing eye irritation. MT
complexes with alphaCD, betaCD, gammaCD, and 2-hydroxypropyl-betaCD (HPbetaCD)
were characterized by phase solubility studies, which demonstrated Higuchi's AL
type phase solubility profiles. The MT/HPbetaCD complex showed the highest MT
solubility (2.75mg/mL). Ocular irritation experiments showed HPbetaCD inclusion
alleviated irritation of the eye. After administration of MT formulations to
rabbit corneas, each harvested cornea was separated into corneal epithelium,
stroma, and endothelium. MT concentrations in the corneal epithelium, stroma, and
endothelium for the F1-treated group were 55.5+/-9.24, 26.7+/-2.66, and 21.1+/
1.77MUM while those for the F2-treated group were 127.2+/-21.01, 43.7+/-16.93,
and 51.0+/-13.91MUM, respectively. Stability studies for 60days showed no
significant change in pH, osmolarity, and MT content. In conclusion, MT/HPbetaCD
formulations can lower irritation, enhance MT stability, and improve therapeutic
efficacy.
PMID- 28694096
TI - A role for random, humidity-dependent epiphytic growth prior to invasion of wheat
by Zymoseptoria tritici.
AB - Zymoseptoria tritici causes Septoria leaf blotch of wheat. The prevailing
paradigm of the Z. tritici-wheat interaction assumes fungal ingress through
stomata within 24-48h, followed by days of symptomless infection. This is
extrapolated from studies testing the mode of fungal ingress under optimal
infection conditions. Here, we explicitly assess the timing of entry, using GFP
tagged Z. tritici. We show that early entry is comparatively rare, and extended
epiphytic growth possible. We test the hypotheses that our data diverge from
earlier studies due to: i. random ingress of Z. tritici into the leaf, with some
early entry events; ii. previous reliance upon fungal stains, combined with poor
attachment of Z. tritici to the leaf, leading to increased likelihood of
observing internal versus external growth, compared to using GFP; iii. use of
exceptionally high humidity to promote entry in previous studies. We combine
computer simulation of leaf-surface growth with thousands of in planta
observations to demonstrate that while spores germinate rapidly on the leaf, over
95% of fungi remain epiphytic, growing randomly over the leaf for ten days or
more. We show that epiphytic fungi are easily detached from leaves by rinsing and
that humidity promotes epiphytic growth, increasing infection rates. Together,
these results explain why epiphytic growth has been dismissed and early ingress
assumed. The prolonged epiphytic phase should inform studies of pathogenicity and
virulence mutants, disease control strategies, and interpretation of the observed
low in planta growth, metabolic quiescence and evasion of plant defences by
Zymoseptoria during symptomless infection.
PMID- 28694097
TI - Behavioural pharmacology of the alpha5-GABAA receptor antagonist S44819:
Enhancement and remediation of cognitive performance in preclinical models.
AB - Previous work has shown that S44819 is a novel GABAA receptor (GABAAR)
antagonist, which is selective for extrasynaptic GABAARs incorporating the alpha5
subunit (alpha5-GABAARs). The present study reports on the preclinical
neuropsychopharmacological profile of S44819. Significantly, no sedative or pro
convulsive side effects of S44819 were found at doses up to 30 mg/kg i.p. Object
recognition (OR) memory in intact mice was enhanced by S44819 (0.3 mg/kg p.o.)
given before the acquisition trial. Mice treated with phencyclidine for two weeks
and tested six days after the cessation of treatment failed to show OR memory.
This deficit was corrected by a single administration of S44819 (0.1, 0.3 or 1
mg/kg p.o.) prior to the acquisition trial. The amnestic effect of ketamine in
rats tested in the eight-arm radial maze (reference and working memory versions)
was blocked by S44819 (3 mg/kg p.o.). Extinction of cued fear was preserved
during treatment with S44819 (3 mg/kg/diem i.p.). Administration of S44819 had no
significant effect in the Vogel-conflict test, the elevated plus maze, the forced
swim, the marble-burying and the tail-suspension tests. In contrast,
anxiolytic/antidepressant-like effects of the compound were found in paradigms
that have mnemonic components, such as social interaction, fear-potentiated
startle and social avoidance induced by negative life experience. In summary,
S44819 enhanced intact recognition memory and ameliorated memory deficits induced
by inhibition of NMDA receptors. Anxiolytic/antidepressant efficacy was limited
to paradigms involving cognitive function. In conclusion, S44819 is a novel
psychoactive pro-cognitive compound with potential as a therapeutic agent in
dementia.
PMID- 28694098
TI - Sleep promoting potential of low dose alpha-Asarone in rat model.
AB - Commonly used hypnotics have undesirable side-effects, especially during
continuous usage. On the other hand, some herbal products, which are used for
prolonged periods, are suggested to have a sleep inducing property, though the
claims have not been validated scientifically. The hypnotic potential of alpha
Asarone, an active principle of Acorus species, was tested in the present study
by first identifying the optimal dose of alpha-Asarone for improving sleep,
followed by studies that evaluated the effect of repeated administration of this
optimal dose for five days on sleep deprived rats. Of all the doses tested (2,
10, 40, 80 and 120 mg/kg), 10 mg/kg alpha-Asarone improved the quality of sleep,
as indicated by an increased NREM bout duration, reduced arousal index, and
decreased bout frequencies of NREM sleep and wakefulness. A marginal decrease in
the hypothalamic and body temperatures was also observed. Higher doses, on the
other hand, not only reduced the quantity and quality of sleep, but also produced
hypothermia. In sleep deprived rats, administration of 10 mg/kg alpha-Asarone for
five consecutive days improved the quality of sleep in contrast to the vehicle
and a known hypnotic midazolam. Improvement in NREM sleep quality was observed
when the difference between the hypothalamic and the body temperature was
minimum. An enhanced association between NREM sleep bout duration and
hypothalamic temperature was also observed after administration of 10 mg/kg alpha
Asarone. This comprehensive study is the first report on the hypnotic property of
alpha-Asarone, which validates its potential to be considered for treatment of
insomnia.
PMID- 28694099
TI - A new dawn in cannabinoid neurobiology: The road from molecules to therapeutic
discoveries.
PMID- 28694093
TI - Functional analyses of major cancer-related signaling pathways in Alzheimer's
disease etiology.
AB - Alzheimer's disease (AD) is an aging-related neurodegenerative disease and
accounts for majority of human dementia. The hyper-phosphorylated tau-mediated
intracellular neurofibrillary tangle and amyloid beta-mediated extracellular
senile plaque are characterized as major pathological lesions of AD. Different
from the dysregulated growth control and ample genetic mutations associated with
human cancers, AD displays damage and death of brain neurons in the absence of
genomic alterations. Although various biological processes predominately
governing tumorigenesis such as inflammation, metabolic alteration, oxidative
stress and insulin resistance have been associated with AD genesis, the
mechanistic connection of these biological processes and signaling pathways
including mTOR, MAPK, SIRT, HIF, and the FOXO pathway controlling aging and the
pathological lesions of AD are not well recapitulated. Hence, we performed a
thorough review by summarizing the physiological roles of these key cancer
related signaling pathways in AD pathogenesis, comprising of the crosstalk of
these pathways with neurofibrillary tangle and senile plaque formation to impact
AD phenotypes. Importantly, the pharmaceutical investigations of anti-aging and
AD relevant medications have also been highlighted. In summary, in this review,
we discuss the potential role that cancer-related signaling pathways may play in
governing the pathogenesis of AD, as well as their potential as future targeted
strategies to delay or prevent aging-related diseases and combating AD.
PMID- 28694101
TI - Fish Oil Supplementation During Pregnancy May Reduce Risk of Persistent Wheeze or
Asthma in Children in First Five Years of Life.
PMID- 28694100
TI - And Then a Miracle Occurs.
PMID- 28694102
TI - Evolution of DMSP (dimethylsulfoniopropionate) biosynthesis pathway: Origin and
phylogenetic distribution in polyploid Spartina (Poaceae, Chloridoideae).
AB - DMSP (dimethylsulfoniopropionate) is an ecologically important sulfur metabolite
commonly produced by marine algae and by some higher plant lineages, including
the polyploid salt marsh genus Spartina (Poaceae). The molecular mechanisms and
genes involved in the DMSP biosynthesis pathways are still unknown. In this
study, we performed comparative analyses of DMSP amounts and molecular
phylogenetic analyses to decipher the origin of DMSP in Spartina that represents
one of the major source of terrestrial DMSP in coastal marshes. DMSP content was
explored in 14 Spartina species using 1H Nuclear Magnetic Resonance (NMR)
spectroscopy and Ultra Performance Liquid Chromatography-Mass Spectrometry (UPLC
MS). Putative genes encoding the four enzymatic steps of the DMSP biosynthesis
pathway in Spartina were examined and their evolutionary dynamics were studied.
We found that the hexaploid lineage containing S. alterniflora, S. foliosa and S.
maritima and their derived hybrids and allopolyploids are all able to produce
DMSP, in contrast to species in the tetraploid clade. Thus, examination of DMSP
synthesis in a phylogenetic context implicated a single origin of this
physiological innovation, which occurred in the ancestor of the hexaploid
Spartina lineage, 3-6MYA. Candidate genes specific to the Spartina DMSP
biosynthesis pathway were also retrieved from Spartina transcriptomes, and
provide a framework for future investigations to decipher the molecular
mechanisms involved in this plant phenotypic novelty that has major ecological
impacts in saltmarsh ecosystems.
PMID- 28694103
TI - COE inhibits vasculogenic mimicry in hepatocellular carcinoma via suppressing
Notch1 signaling.
AB - ETHNOPHARMACOLOGICAL RELEVANCE: Vasculogenic mimicry (VM) has been suggested to
be present in various malignant tumors and associated with tumor nutrition supply
and metastasis, leading to poor prognosis of patients. Notch1 has been
demonstrated to contribute to VM formation in hepathocellular carcinoma (HCC).
Celastrus orbiculatus extract (COE), a mixture of 11 terpenoids isolated from the
Chinese Herb Celastrus orbiculatus Vine, has been suggested to be effective in
cancer treatment. AIM OF THE STUDY: In the current study, experiments were
carried out to examine the effect of COE on VM formation and HCC tumor growth
both in vitro and in vivo. MATERIALS AND METHODS: CCK-8 assay and Nikon live-work
station were used to observe the viability of malignant cells treated with COE.
Cell invasion was examined using Transwell. Matrigel was used to establish a 3-D
culture condition for VM formation. Changes of mRNA and protein expression were
examined by RT-PCR and Western Blot respectively. Tumor growth in vivo was
monitored using in vivo fluorescence imaging device. PAS-CD34 dual staining and
electron microscopy were used to observe VM formation. Immunohistochemical
staining (IHC) was used to examine Notch1 and Hes1 expression in tumor tissues.
RESULTS: Results showed that COE can inhibit HCC cells proliferation and invasion
in a concentration-dependent manner. VM formation induced by TGF-beta1 was
blocked by COE. In mouse xenograft model, COE inhibited tumor growth and VM
formation. Both in vitro and in vivo studies showed that COE can downregulate
expression of Notch1 and Hes1. CONCLUSION: The current results indicate that COE
can inhibit VM formation and HCC tumor growth by downregulating Notch1 signaling.
This study demonstrates that COE is superior to other anti-angiogenesis agents
and can be considered as a promising candidate in HCC treatment.
PMID- 28694104
TI - Antimicrobial natural product research: A review from a South African perspective
for the years 2009-2016.
AB - ETHNOPHARMACOLOGICAL RELEVANCE: This review provides information on the
antimicrobial research which has taken place on South African natural products
for the last eight years (2009-2016). This important field is the backbone of all
studies involving the use of medicinal plants against infectious diseases and
hence can form the mainstay for future studies. MATERIALS AND METHODS: All
publications within the years 2009-2016 were considered. Exclusion criteria were
studies not involving South African medicinal natural products and those
publications where full articles could not be accessed. An overview of the most
common experimental methods used and new advances in terms of antimicrobial
investigations are provided. Disease categories selected for further
investigation were skin and wounds, respiratory, gastrointestinal, sexually
transmitted and ophthalmic infections amongst others. Alternate natural products
and combinations studies were also included. RESULTS: The minimum inhibitory
concentration (MIC) was the most commonly used experimental method to determine
antimicrobial activity. Staphylococcus aureus was the most commonly tested skin
pathogen and Klebsiella pneumoniae was the most common pathogen implicated in
respiratory disorders. Only 20% of gastrointestinal studies included commonly
implicated pathogens such as Shigella flexneri and Campylobacter species.
CONCLUSION: Multidisciplinary studies have emerged as a strong support for
antimicrobial investigations and show the importance of including toxicity when
studying antimicrobial efficacy. Alternate approaches (for example biofilms and
quorum sensing) at examining antimicrobial effects are encouraged. Studies on
resistant strains require more insight and future recommendations should look at
consistent dosing and investigations on compound interactions amongst others.
PMID- 28694105
TI - CEP131 indicates poor prognosis and promotes cell proliferation and migration in
hepatocellular carcinoma.
AB - Centrosomal proteins have been implicated in the progression of human diseases.
CEP131 plays important roles in centrosome duplication and genome stability, but
its role in cancers remains largely unknown. Here, we showed that CEP131
expression was increased in hepatocellular carcinoma (HCC), compared to the
paracarcinoma tissues, at both mRNA and protein levels. High CEP131 expression
was closely associated with tumor size (P=0.020), tumor capsule (P=0.043), TNM
stage (P=0.007) and tumor differentiation (P=0.019). Furthermore, patients with
high expression of CEP131 were accompanied with worse overall and disease-free
survivals in our and TCGA cohorts consisting of a total of 802 cases. The
prognostic value of CEP131 was further confirmed by stratified survival analysis.
Multivariate cox regression model indicated that CEP131 was an independent factor
for overall survival (hazard ratio=1.762, 95% confident interval: 1.443-2.151,
P<0.001). In vitro data demonstrated that nucleophosmin (NPM) physically bound to
CEP131 and maintained its protein stability. Overexpression of CEP131 in HCC cell
lines enhanced cell proliferation and migration, whereas the knockdown of CEP131
led to the opposite phenotypes. Further studies demonstrated that CEP131
exhibited oncogenic activity via activation of PI3K/AKT signaling pathway. Taken
together, our findings suggest CEP131 serves as a potential prognostic biomarker
in HCC, and functions as an oncogene in this deadly disease.
PMID- 28694106
TI - Neural and non-neural related properties in the spastic wrist flexors: An
optimization study.
AB - Quantifying neural and non-neural contributions to increased joint resistance in
spasticity is essential for a better understanding of its pathophysiological
mechanisms and evaluating different intervention strategies. However, direct
measurement of spasticity-related manifestations, e.g., motoneuron and
biophysical properties in humans, is extremely challenging. In this vein, we
developed a forward neuromusculoskeletal model that accounts for dynamics of
muscle spindles, motoneuron pools, muscle activation and musculotendon of wrist
flexors and relies on the joint angle and resistant torque as the only input
measurement variables. By modeling the stretch reflex pathway, neural and non
neural related properties of the spastic wrist flexors were estimated during the
wrist extension test. Joint angle and resistant torque were collected from 17
persons with chronic stroke and healthy controls using NeuroFlexor, a motorized
force measurement device during the passive wrist extension test. The model was
optimized by tuning the passive and stretch reflex-related parameters to fit the
measured torque in each participant. We found that persons with moderate and
severe spasticity had significantly higher stiffness than controls. Among
subgroups of stroke survivors, the increased neural component was mainly due to a
lower muscle spindle rate at 50% of the motoneuron recruitment. The motoneuron
pool threshold was highly correlated to the motoneuron pool gain in all
subgroups. The model can describe the overall resistant behavior of the wrist
joint during the test. Compared to controls, increased resistance was
predominantly due to higher elasticity and neural components. We concluded that
in combination with the NeuroFlexor measurement, the proposed
neuromusculoskeletal model and optimization scheme served as suitable tools for
investigating potential parameter changes along the stretch-reflex pathway in
persons with spasticity.
PMID- 28694107
TI - Effects of non-physiological blood pressure artefacts on cerebral autoregulation.
AB - Cerebral autoregulation refers to the brain's regulation mechanisms that aim to
maintain the cerebral blood flow approximately constant. It is often assessed by
the autoregulation index (ARI). ARI uses arterial blood pressure and cerebral
blood flow velocity time series to produce a ten-scale index of autoregulation
performance (0 denoting the absence of and 9 the strongest autoregulation).
Unfortunately, data are rarely free from various artefacts. Here, we consider
four of the most common non-physiological blood pressure artefacts (saturation,
square wave, reduced pulse pressure and impulse) and study their effects on ARI
for a range of different artefact sizes. We show that a sufficiently large
saturation and square wave always result in ARI reaching the maximum value of 9.
The pulse pressure reduction and impulse artefact lead to more diverse behaviour.
Finally, we characterized the critical size of artefacts, defined as the minimum
artefact size that, on average, leads to a 10% deviation of ARI.
PMID- 28694108
TI - Increased blood pressure variability upon standing up improves reproducibility of
cerebral autoregulation indices.
AB - Dynamic cerebral autoregulation, that is the transient response of cerebral blood
flow to changes in arterial blood pressure, is currently assessed using a variety
of different time series methods and data collection protocols. In the continuing
absence of a gold standard for the study of cerebral autoregulation it is unclear
to what extent does the assessment depend on the choice of a computational method
and protocol. We use continuous measurements of blood pressure and cerebral blood
flow velocity in the middle cerebral artery from the cohorts of 18 normotensive
subjects performing sit-to-stand manoeuvre. We estimate cerebral autoregulation
using a wide variety of black-box approaches (including the following six
autoregulation indices ARI, Mx, Sx, Dx, FIR and ARX) and compare them in the
context of reproducibility and variability. For all autoregulation indices,
considered here, the intra-class correlation was greater during the standing
protocol, however, it was significantly greater (Fisher's Z-test) for Mx (p <
0.03), Sx (p < 0.003) and Dx (p < 0.03). In the specific case of the sit-to-stand
manoeuvre, measurements taken immediately after standing up greatly improve the
reproducibility of the autoregulation coefficients. This is generally coupled
with an increase of the within-group spread of the estimates.
PMID- 28694109
TI - Mathematical modelling of the maternal cardiovascular system in the three stages
of pregnancy.
AB - In this study, a mathematical model of the female circulation during pregnancy is
presented in order to investigate the hemodynamic response to the cardiovascular
changes associated with each trimester of pregnancy. First, a preliminary lumped
parameter model of the circulation of a non-pregnant female was developed,
including the heart, the systemic circulation with a specific block for the
uterine district and the pulmonary circulation. The model was first tested at
rest; then heart rate and vascular resistances were individually varied to verify
the correct response to parameter alterations characterising pregnancy. In order
to simulate hemodynamics during pregnancy at each trimester, the main changes
applied to the model consisted in reducing vascular resistances, and
simultaneously increasing heart rate and ventricular wall volumes. Overall,
reasonable agreement was found between model outputs and in vivo data, with the
trends of the cardiac hemodynamic quantities suggesting correct response of the
heart model throughout pregnancy. Results were reported for uterine hemodynamics,
with flow tracings resembling typical Doppler velocity waveforms at each stage,
including pulsatility indexes. Such a model may be used to explore the changes
that happen during pregnancy in female with cardiovascular diseases.
PMID- 28694110
TI - Predictors of In-Hospital Mortality after Decompressive Hemicraniectomy for
Malignant Ischemic Stroke.
AB - OBJECTIVE: The purpose of this retrospective multicenter, pooled-data analysis
was to determine the factors associated with in-hospital mortality in
decompressive hemicraniectomy (DHC) for malignant middle cerebral artery (MMCA)
stroke. PATIENTS AND METHODS: The authors reviewed pooled DHC database from 3
countries for patients with MMCA with hospital mortality in spite of DHC to
identify factors that predicted in-hospital mortality after DHC. The identified
factors were applied to the group of patients who were selected for DHC but
either refused surgery and died or stabilized and did not undergo DHC. FINDINGS:
There were 137 patients who underwent DHC. Multiple logistic regression analysis
showed middle cerebral artery (MCA) with additional infarcts (odds ratio [OR],
7.9: 95% confidence interval [CI], 2.4-26; P = .001), preoperative midline shift
of septum pellucidum of 1 cm or more (OR, 3.83: 95% CI, 1.13-12.96; P = .031),
and patients who remained unconscious on day 7 postoperatively (8.82: 95% CI; OR,
1.08-71.9; P = .042) were significant independent predictors for in-hospital
mortality. The identified factors were applied to the group of MMCA patients not
operated (n = 19 refused, n = 47 stabilized) single (P < .001), and two
predictive factors (P < .001) were significantly more common in patients who
died. Whereas two predicative factors were identified in only 9%-18.2% of
survivors, the presence of all three predictive factors was seen only in patients
who expired (P < .001). The Hosmer-Lemeshow goodness-of-fit statistics (chi
square = 4.65; P value = .589) indicate that the model adequately describes the
data. CONCLUSION: Direct physical factors, such as MCA with additional territory
infarct, extent of midline shift, and postoperative consciousness level, bore a
significant relationship to in-hospital mortality in MMCA patients undergoing
DHC.
PMID- 28694111
TI - The Pathophysiology of Watershed Infarction: A Three-Dimensional Time-of-Flight
Magnetic Resonance Angiography Study.
AB - BACKGROUND: Most of the time, watershed infarcts (WIs) involve steno-occlusive
carotid disease. The pathophysiological mechanism could be predicted by their
pattern: internal WIs (IWIs) are thought to be due to hemodynamic impairment in
contrast to cortical WIs (CWIs), which are more likely to be caused by
microembolic phenomena. We used a 3D time-of-flight (TOF) magnetic resonance
angiography (MRA) study to assess this hypothesis. METHODS: In 45 consecutive
patients with a recent WI and ipsilateral cervical carotid stenosis, clinical and
radiological data were obtained retrospectively. 3D TOF MRA were analyzed both
qualitatively and quantitatively (internal carotid and anterior, middle and
posterior cerebral arteries). Then, 2 groups were determined depending on their
radiological patterns: WIs with (IWI+) or without (IWI-) an internal watershed.
RESULTS: Thirty-two of the 45 patients (71%) had IWIs that were or were not
associated with CWIs (IWI+), while 13 patients (29%) had only CWIs (IWI-). There
was no significant relationship between the radiological pattern and the
demographic data, the cardiovascular risk factors, or the degree of stenosis.
However, IWI+ patients more frequently had motor weakness (P = .03) than CWI
patients. An ipsilateral reduced middle cerebral artery intensity on 3D TOF MRA
in both qualitative and quantitative analyses was significantly associated with
IWI+. Instead within IWI-, no significantly reduced signal intensity was found.
CONCLUSION: These findings originally support the view that IWIs are mainly
caused by a hemodynamic impairment related to carotid stenosis, whereas CWIs are
mostly due to a microembolic mechanism. 3D TOF MRA, which gives pertinent
information on pathophysiology on IWIs, can help in decision making.
PMID- 28694112
TI - Atomic force microscopy as a tool for assessing the cellular elasticity and
adhesiveness to identify cancer cells and tissues.
AB - From the first experiments of the atomic force microscopy (AFM) with biological
samples, the range of its potential applications grows extensively. One of them
is the use of AFM to characterize biophysical fingerprints of cancer progression
in search of non-labelled biomarkers of the disease. The technique offers various
functionalities, starting from surface imaging to detection of interaction
forces, delivering quantitative parameters that can describe changes
characteristic for various diseases, including cancer. In this review, the
special emphasis was laid on these studies that compare the AFM-derived
properties of reference and cancerous cells using all functionalities from
cellular deformability measurements to quantification of the interaction forces
at the single-molecule and single-cell levels. Despite the large effort and
evidence of the microscope applicability to detect pathologically altered cells,
there are still practical challenges remained to be solved before AFM can be
implemented for routine cancer tracking and diagnosis. To-date, the AFM can be
used to achieve a better understanding of cancer-related processes and mechanisms
that could be further employed to design high-resolution clinical assays in a
quantitative way.
PMID- 28694113
TI - Pumping up the volume - vacuole biogenesis in Arabidopsis thaliana.
AB - Plant architecture follows the need to collect CO2, solar energy, water and
mineral nutrients via large surface areas. It is by the presence of a central
vacuole that fills much of the cell volume that plants manage to grow at low
metabolic cost. In addition vacuoles buffer the fluctuating supply of essential
nutrients and help to detoxify the cytosol when plants are challenged by harmful
molecules. Despite their large size and multiple important functions, our
knowledge of vacuole biogenesis and the machinery underlying their amazing
dynamics is still fragmentary. In this review, we try to reconcile past and
present models for vacuole biogenesis with the current knowledge of multiple
parallel vacuolar trafficking pathways and the molecular machineries driving
membrane fusion and organelle shape.
PMID- 28694114
TI - Epigenetic dysregulation of protocadherins in human disease.
AB - Protocadherins (Pcdhs) are a group of cell-cell adhesion molecules that are
highly expressed in the nervous system and have a major function in dendrite
development and neural circuit formation. However, the role protocadherins play
in human health and disease remains unclear. Several recent studies have
associated epigenetic dysregulation of protocadherins with possible implications
for disease pathogenesis. In this review, we briefly recap the various epigenetic
mechanisms regulating protocadherin genes, particularly the clustered Pcdhs. We
further outline research describing altered epigenetic regulation of
protocadherins in neurological and psychiatric disorders, as well as in cancer
and during aging. We additionally present preliminary data on DNA methylation
dynamics of clustered protocadherins during fetal brain development, as well as
the epigenetic differences distinguishing adult neuronal and glial cells. A
deeper understanding of the role of protocadherins in disease is crucial for
designing novel diagnostic tools and therapies targeting brain disorders.
PMID- 28694115
TI - Differences in urethral dosimetry between CT and MR imaging in multichannel
vaginal cylinder brachytherapy.
AB - PURPOSE: In image-based brachytherapy (IBBT), the dosimetry of small structures
may be particularly sensitive to changes in contouring between imaging
modalities. We therefore sought to characterize differences in urethral dosimetry
in vaginal brachytherapy based on contouring on MRI vs. CT. METHODS AND
MATERIALS: We retrospectively identified our most recent 15 patients treated with
intracavitary brachytherapy for distal vaginal malignancies. On T2-weighted MRI,
both the lumen and urethral wall were contoured. On CT, the urethral lumen alone
was contoured, as the wall is indistinguishable from surrounding tissue. High
dose-rate (HDR) IBBT plans were generated for all patients. RESULTS: Mean
urethral volume was higher on MRI than CT at 3.7 cc vs. 1.1 cc (p < 0.0005). As a
result, there were statistically significant increases on MRI in D0.1cc and
D0.5cc, as well as EQD2 D0.1cc and EQD2 D0.5cc when applied to a full course of
treatment (45 Gy EBRT + 25 Gy IBBT). CONCLUSIONS: We have quantified the expected
differences in urethral volume and dosimetry when contoured on MRI vs. CT.
Inclusion of the urethral wall on MRI, with its average thickness of 2.2 mm,
likely more accurately reflects the true organ at risk and results in an increase
in reported dose compared to CT.
PMID- 28694116
TI - Effect of bladder distension on doses to organs at risk in Pulsed-Dose-Rate 3D
image-guided adaptive brachytherapy for locally advanced cervical cancer.
AB - PURPOSE: To evaluate the impact of bladder distension on doses to organs at risk
in patients treated with 3D image-guided adaptive pulsed-dose-rate (PDR)
brachytherapy (BT) for locally advanced cervical cancer. METHODS AND MATERIALS:
Twenty-two patients who had previously been treated by external beam radiation
therapy (EBRT), underwent BT treatment planning to a pelvic MRI (or a CT scan in
case of contraindication) after their bladder was filled with 100 cc of
physiological saline (full bladder). This was immediately followed by a CT scan
after emptying of the bladder. A fusion of these two examinations was conducted,
and the dosimetry was duplicated for the study with an empty bladder.
Equieffective doses of 2 Gy per fraction from EBRT and BT of
bladder/rectum/sigmoid colon/small bowel were compared. RESULTS: A full bladder
condition was found to be non-inferior in terms of the bladder D2cc (a difference
of -0.9 Gy; 97.5% CI [-infinity; 2.6]), and it resulted in a reduction in the
bladder D0.1cc (p = 0.038). Bladder expansion resulted in a significant reduction
of maximum doses received by the small bowel, both in terms of the D0.1cc (51.2
Gy vs. 63.4 Gy, p < 0.001) and the D2cc (48.5 Gy vs. 53.6 Gy, p < 0.001). A
negative correlation was seen between the difference in the small bowel D2cc and
the body mass index; (r = -0.55; p = 0.008). No differences were noted in regard
to doses to the rectum and sigmoid colon. CONCLUSIONS: Bladder distension with
100 cc of physiological saline can reduce maximum doses received by the small
bowel without the alteration of the doses received by the other organs at risk
during a 3D image-guided adaptive PDR BT for locally advanced cervical cancer.
However, the maintenance of a predefined bladder volume is difficult to achieve
with PDR BT, whereas it could be easily managed before each session in case of
high-dose-rate BT.
PMID- 28694117
TI - Brachytherapy boost for prostate cancer: A potential conflict of disinterest.
PMID- 28694118
TI - Automatic classification of RDoC positive valence severity with a neural network.
AB - OBJECTIVE: Our objective was to develop a machine learning-based system to
determine the severity of Positive Valance symptoms for a patient, based on
information included in their initial psychiatric evaluation. Severity was rated
on an ordinal scale of 0-3 as follows: 0 (absent=no symptoms), 1 (mild=modest
significance), 2 (moderate=requires treatment), 3 (severe=causes substantial
impairment) by experts. MATERIALS AND METHODS: We treated the task of assigning
Positive Valence severity as a text classification problem. During development,
we experimented with regularized multinomial logistic regression classifiers,
gradient boosted trees, and feedforward, fully-connected neural networks. We
found both regularization and feature selection via mutual information to be very
important in preventing models from overfitting the data. Our best configuration
was a neural network with three fully connected hidden layers with rectified
linear unit activations. RESULTS: Our best performing system achieved a score of
77.86%. The evaluation metric is an inverse normalization of the Mean Absolute
Error presented as a percentage number between 0 and 100, where 100 means the
highest performance. Error analysis showed that 90% of the system errors involved
neighboring severity categories. CONCLUSION: Machine learning text classification
techniques with feature selection can be trained to recognize broad differences
in Positive Valence symptom severity with a modest amount of training data (in
this case 600 documents, 167 of which were unannotated). An increase in the
amount of annotated data can increase accuracy of symptom severity classification
by several percentage points. Additional features and/or a larger training corpus
may further improve accuracy.
PMID- 28694119
TI - Recurrent neural networks for classifying relations in clinical notes.
AB - We proposed the first models based on recurrent neural networks (more
specifically Long Short-Term Memory - LSTM) for classifying relations from
clinical notes. We tested our models on the i2b2/VA relation classification
challenge dataset. We showed that our segment LSTM model, with only word
embedding feature and no manual feature engineering, achieved a micro-averaged f
measure of 0.661 for classifying medical problem-treatment relations, 0.800 for
medical problem-test relations, and 0.683 for medical problem-medical problem
relations. These results are comparable to those of the state-of-the-art systems
on the i2b2/VA relation classification challenge. We compared the segment LSTM
model with the sentence LSTM model, and demonstrated the benefits of exploring
the difference between concept text and context text, and between different
contextual parts in the sentence. We also evaluated the impact of word embedding
on the performance of LSTM models and showed that medical domain word embedding
help improve the relation classification. These results support the use of LSTM
models for classifying relations between medical concepts, as they show
comparable performance to previously published systems while requiring no manual
feature engineering.
PMID- 28694120
TI - Ecological preferences of Metarhizium spp. from Russia and neighboring
territories and their activity against Colorado potato beetle larvae.
AB - Thirty-four isolates of Metarhizium spp. from Russian collections were genotyped
using 5' EF-1alpha gene sequence analysis. Four species were identified, of which
M. robertsii and M. brunneum were the most frequent, whereas M. anisopliae and M.
pemphigum were sporadic. Radial growth studies in the temperature range of 10-40
degrees C revealed that growth at high temperatures (35-37.5 degrees C) was
inherent for M. robertsii isolates but not for M. brunneum isolates. In contrast,
M. brunneum isolates were more active at cold temperatures (10 degrees C)
compared to M. robertsii. Virulence was evaluated against larvae of the Colorado
potato beetle (CPB), Leptinotarsa decemlineata Say, under two regimes: humid (21
degrees C, 80% relative humidity (RH)) and arid (31 degrees C, 55% RH). M.
brunneum isolates were less virulent compared to M.robertsii under both regimes.
M. robertsii activity did not differ under the two regimes, but M. brunneum was
less virulent under the arid regime compared to the humid one. A field experiment
under natural conditions (steppe zone of Western Siberia) with daily ranges of 10
43 degrees C and 13-98% RH showed that M. robertsii was significantly more active
than M. brunneum against CPB larvae.
PMID- 28694121
TI - Quasi-experimental study designs series-paper 1: introduction: two historical
lineages.
AB - OBJECTIVES: The objective of this study was to contrast the historical
development of experiments and quasi-experiments and provide the motivation for a
journal series on quasi-experimental designs in health research. STUDY DESIGN AND
SETTING: A short historical narrative, with concrete examples, and arguments
based on an understanding of the practice of health research and evidence
synthesis. RESULTS: Health research has played a key role in developing today's
gold standard for causal inference-the randomized controlled multiply blinded
trial. Historically, allocation approaches developed from convenience and
purposive allocation to alternate and, finally, to random allocation. This
development was motivated both by concerns for manipulation in allocation as well
as statistical and theoretical developments demonstrating the power of
randomization in creating counterfactuals for causal inference. In contrast to
the sequential development of experiments, quasi-experiments originated at very
different points in time, from very different scientific perspectives, and with
frequent and long interruptions in their methodological development. Health
researchers have only recently started to recognize the value of quasi
experiments for generating novel insights on causal relationships. CONCLUSION:
While quasi-experiments are unlikely to replace experiments in generating the
efficacy and safety evidence required for clinical guidelines and regulatory
approval of medical technologies, quasi-experiments can play an important role in
establishing the effectiveness of health care practice, programs, and policies.
The papers in this series describe and discuss a range of important issues in
utilizing quasi-experimental designs for primary research and quasi-experimental
results for evidence synthesis.
PMID- 28694122
TI - The risk of bias in systematic reviews tool showed fair reliability and good
construct validity.
AB - OBJECTIVE: There is a movement from generic quality checklists toward a more
domain-based approach in critical appraisal tools. This study aimed to report on
a first experience with the newly developed risk of bias in systematic reviews
(ROBIS) tool and compare it with A Measurement Tool to Assess Systematic Reviews
(AMSTAR), that is, the most common used tool to assess methodological quality of
systematic reviews while assessing validity, reliability, and applicability.
STUDY DESIGN AND SETTING: Validation study with four reviewers based on 16
systematic reviews in the field of occupational health. RESULTS: Interrater
reliability (IRR) of all four raters was highest for domain 2 (Fleiss' kappa
kappa = 0.56) and lowest for domain 4 (kappa = 0.04). For ROBIS, median IRR was
kappa = 0.52 (range 0.13-0.88) for the experienced pair of raters compared to
kappa = 0.32 (range 0.12-0.76) for the less experienced pair of raters. The
percentage of "yes" scores of each review of ROBIS ratings was strongly
correlated with the AMSTAR ratings (rs = 0.76; P = 0.01). CONCLUSION: ROBIS has
fair reliability and good construct validity to assess the risk of bias in
systematic reviews. More validation studies are needed to investigate reliability
and applicability, in particular.
PMID- 28694123
TI - Series: Pragmatic trials and real world evidence: Paper 5. Usual care and real
life comparators.
AB - Pragmatic trials may deliver real-world evidence on the added value of new
medications compared with usual care and inform decision making earlier in
development. This fifth paper in a series on pragmatic trials in the Journal
discusses usual care as a comparator and the allocation of treatment strategies.
The allocation and implementation of treatment strategies should resemble
clinical practice as closely as possible. Randomization at the level of the site,
as opposed to at the individual level, may be preferred. Data analysis according
to the intention-to-treat principle is recommended, and crossover between
treatment arms and strong treatment preferences may be accounted for in the study
design in specific situations. Although usual care is the comparator of choice,
this may differ substantially between centers and countries complicating
comparator choice. Using clinical guidelines to define usual care can be helpful
in standardizing comparator treatments; however, this may decrease the
applicability of the results to real-life settings. Conversely, using multiple
usual-care treatment arms will increase the complexity of the study. The specific
objectives of the trial and design choices should be discussed with all
stakeholders to realize the full potential of the pragmatic trial.
PMID- 28694124
TI - The standardization of 5 immunoassays for anti-Toxoplasma immunoglobulin G(IgG).
AB - BACKGROUND: Quantitative immunoassays to detect IgG antibodies are the most
commonly used tests for diagnosing toxoplasmosis. We investigated the current
state of standardization of quantitative immunoassays used to measure anti
Toxoplasma IgG levels. METHODS: Four fully automated immunoassays (Architect
i4000ISR, Immulite 2000 Xpi, Siemens; Liaison, DiaSorin; Cobas e601, Roche) and
one manual immunoassay (ELISA classic Toxo IgG, Virion Serion) were performed on
the following: individual patient serum samples, the WHO international standards,
control samples, and calibrators provided by 5 immunoassay manufacturers.
Statistical analysis was used to illustrate the results. RESULTS: No perfect
correlation (slope=1.0) was found between any 2 assays. Large differences in anti
Toxoplasma IgG titers were observed among the 5 immunoassays using serum samples
from individual patients. Using IS 01/600 as a calibrator minimized the inter
assay variability of anti-Toxoplasma IgG values CONCLUSIONS: There is still
significant effort needed towards standardization of anti-Toxoplasma IgG
quantitative immunoassays.
PMID- 28694125
TI - A fully analytical approach to investigate the electro-viscous effect of the
endothelial glycocalyx layer on the microvascular blood flow.
AB - BACKGROUND: Recently, the glycocalyx lining the endothelial surface has emerged
as a structure of fundamental importance to a wide range of phenomena that has
undeniable effect on cardiovascular health and disease. With respect to the blood
flow in small vessels, it has been experimentally reported that the glycocalyx
layer causes additional resistance to the flow. METHODS: The hypothesis of
glycocalyx resistance against the blood flow, considered as two-phase layer fluid
through a small blood vessel, was theoretically evaluated. To do that, a very
thin electric double layer (EDL) was considered and the fluid flow was modeled by
the well-known Poisson and Boltzmann equations in micro-fluidics alongside the
general Navier-Stokes equation. Finally, a complete analytical solution for this
particular case was developed. RESULTS: The results confirmed the previous
findings indicated that the negatively charged glycocalyx layer has no effect on
the macro/micro scale blood flow. Here and in the nano-scale, slightly influence
was observed and reported in this study. CONCLUSION: Moreover, more details about
the thin electrically significant layer, close to the EDL, would be delineate to
better recognition of electro-viscous effect caused by the endothelial glycocalyx
near microvascular walls.
PMID- 28694126
TI - Phenolic acids from Balanophora involucrata and their bioactivities.
AB - The bioactive substance investigation of Balanophora involucrata obtained 15
phenolic acids, including 5 new compounds (1-3, 8, 9), which were determined by
various spectroscopic data analyses. Most isolated compounds displayed inhibitory
effects on alpha-Glucosidase in vitro. For the potential inhibitors 8 (1.95MUM)
and 10 (9.02MUM), the inhibition kinetics have been studied, which gave the Ki
values as 0.68, 3.15MUM respectively. And, in silico docking analyses have been
performed to investigate the inhibitory mechanism of compounds 8 and 10.
Additionally, most isolated compounds showed anti-oxidant activities in the DPPH
scavenging assay. New compound 8 also could inhibit the acetyl transfer activity
of GlmU moderately with the IC50 value of 18.21MUM, which was a new antibacterial
target.
PMID- 28694127
TI - Fish adjust aggressive behavior to audience size with limited information on
bystanders' fighting ability.
AB - In a social environment, individual behavior is modulated by surrounding
observers (a phenomenon known as the audience effect). Here, we used mirrors to
test the effect of two audience sizes (one virtual bystander vs. three virtual
bystanders) on the aggressive behavior of a focal fish when bystander's fighting
ability was not clear (i.e., information about the ability of virtual
conspecifics limited by their mirror images). We found that the Nile tilapia, a
cichlid fish, responds to its image as an audience by reducing overt aggression
in the presence of larger audience.
PMID- 28694128
TI - MicroRNA-221-3p promotes pulmonary artery smooth muscle cells proliferation by
targeting AXIN2 during pulmonary arterial hypertension.
AB - Pulmonary arterial hypertension (PAH) is a pathological condition characterized
by excessive cell proliferation and migration of pulmonary arterial smooth muscle
cells (PASMC). PAH pathogenesis shares similarities with cancers such as
excessive cell proliferation and apoptosis resistance. A previous study by our
group revealed that decreased expression of a tumor suppressor-AXIN2 (Axis
inhibition protein 2) was responsible for enhanced PASMC proliferation and
suppressed apoptosis. Nevertheless, the mechanisms that regulate the
downregulation of AXIN2 in PAH remain elusive. Data from the present study
demonstrated that miR-221-3p acts as an upstream regulator of AXIN2 and functions
to induce PASMC proliferation. We first showed that miR-221-3p expression was
elevated in lung tissue and PASMC of PAH patients as well as in animal models of
PAH. Human PASMC were transfected with a miR-221-3p mimic and miR-221-3p
inhibitor, respectively, and their effects on the proliferation and migration was
assessed using BrdU incorporation, PCNA staining and wound healing assays. In
addition, we investigated the molecular mechanism through which miR-221-3p
contributes to cell proliferation in PASMC and identified AXIN2 as a direct
target gene of miR-221-3p by dual luciferase reporter gene assays, qRT-qPCR and
western blotting. Furthermore, we found that ectopic expression of AXIN2 or
pharmacological inhibition of beta-catenin by XAV-939 can attenuate the effect of
miR-221-3p on cell proliferation in PASMC. Moreover, intravenous injection of miR
221-3p inhibitor attenuated the progression of SU5416-hypoxia-induced PAH in
rats. The results of the present study identified a new regulatory axis in which
miR-221-3p and AXIN2 regulate the proliferation of PASMC.
PMID- 28694129
TI - Hepatocellular Carcinoma Surveillance.
PMID- 28694130
TI - Bowel Damage in Patients With Long-term Crohn's Disease, Assessed by Magnetic
Resonance Enterography and the Lemann Index.
AB - BACKGROUND & AIMS: Magnetic resonance enterography (MRE) is used to evaluate the
extent and complications of Crohn's disease (CD). MRE results are used in
calculation of the Lemann index (LI) score, which quantifies bowel damage. The
long-term outcomes of CD are uncertain; we aimed to assess bowel disease and
damage in patients with CD for 20 years using MRE and the LI. METHODS: We
performed a follow-up analysis of a population-based cohort of 237 patients in
southeastern Norway diagnosed with CD from 1990 to 1993. Twenty years after
diagnosis, 156 attended the evaluation in which they were offered routine
clinical blood tests and colonoscopies. Ninety-six patients were examined by MRE
and LI scores were calculated. The independent association of the LI score with
clinical variables was examined by univariate analysis. RESULTS: Sixty-five
patients (67.7%) had CD manifestations based on findings from MRE (36.9%),
colonoscopy (29.2%), or both (33.9%). MRE findings changed disease classification
for 8 patients (8.3%). The median LI score was 4.6 (interquartile range, 17.5)
and associated with younger age (P = .02), complicated ileocolonic phenotype (P <
.001), and use of biologic (P < .001), or immunosuppressant therapies (P = .045).
Factors independently associated with LI score during the follow-up period were
age, complicated disease, use of medication, and markers of inflammation.
CONCLUSIONS: In a population-based study of 237 patients with CD in Norway, we
found that almost 68% had imaging features of CD, half of which were only
detectable by MRE. LI score associated with ongoing active disease. Young age,
complicated disease, and persistent inflammation were associated with bowel
damage.
PMID- 28694131
TI - Diagnosing Liver Fibrosis and Cirrhosis: Serum, Imaging, or Tissue?
PMID- 28694132
TI - Inflammatory Bowel Disease and Small Bowel Cancer Risk, Clinical Characteristics,
and Histopathology: A Population-Based Study.
AB - BACKGROUND & AIMS: Inflammatory bowel disease (IBD) may increase risk of small
bowel cancer (SBC). However, little is known of the characteristics and features
of IBD-SBC, due to a low number of cases worldwide. We performed a population
based study of IBD and SBC to calculate risk and increase our understanding of
clinical characteristics and histopathological and molecular features. METHODS:
The study population consisted of all individuals aged 16 years or older living
in Denmark during 1978-2010. Through linkage between national registers and
subsequent scrutiny of medical records and pathology descriptions, we identified
40 cases of IBD-SBC. Risk was calculated by standardized incidence ratio (SIR)
(observed/expected); patient characteristics were derived from medical files, and
surgery specimens were obtained from hospitals nationwide for histopathological
and molecular analyses. RESULTS: During 241,620 person-years of follow-up, 23
patients with Crohn's disease developed small bowel adenocarcinoma (SIR, 14.38;
95% confidence interval, 8.78-22.20) and 9 developed neuroendocrine tumors (SIR,
6.83; 95% confidence interval, 3.13-12.97). No significantly increased risk of
SBC was found among patients with ulcerative colitis. Most patients with SBC had
moderate-to-severe Crohn's disease with small bowel and upper gastrointestinal
involvement. Assessment of surgical specimens of small bowel adenocarcinomas
revealed a clear transition from inflammation to dysplasia and cancer, whereas no
tumors had evidence of microsatellite instability. CONCLUSIONS: In a population
based study of patients in Denmark with IBD and SBC, we found risk of
adenocarcinomas and neuroendocrine tumors to be increased among persons with
Crohn's disease. Most patients with IBD-SBC had extensive IBD of moderate-to
severe activity. Adenocarcinomas appeared to develop via an inflammation
dysplasia-carcinoma pathway, but differed from IBD-related colorectal
adenocarcinomas in their molecular features.
PMID- 28694133
TI - Risk of Ectopic Pregnancy in Women With Inflammatory Bowel Disease: A 22-Year
Nationwide Cohort Study.
AB - BACKGROUND & AIMS: Few data are available on adverse events of pregnancy in women
with inflammatory bowel diseases (IBD), such as ectopic pregnancy. We assessed
the risk of ectopic pregnancy in pregnancies of women in Denmark with IBD
compared with those without IBD over a 22-year period. We also examined the
disease-specific risks of ectopic pregnancies in pregnancies of women with
ulcerative colitis (UC) or Crohn's disease (CD) who underwent IBD-related
surgical procedures. METHODS: We performed a retrospective study of all women of
child-bearing age (ages, 15-50 y) registered in the Danish National Patient
Registry with at least 1 pregnancy during the period from January 1994 through
December 31, 2015. We collected data on all women with an ectopic pregnancy,
hydatidiform mole, miscarriages (spontaneous and other abortions, including
abnormal pregnancy products, missed abortion, and pregnancy without a fetus),
induced abortions, and births in women with and without IBD. Our study population
included 7548 pregnancies in women with UC, 6731 pregnancies in women with CD,
and 1,832,732 pregnancies in women without IBD. We controlled for multiple
covariates, including pelvic and abdominal surgery. RESULTS: Women with CD had a
greater risk of ectopic pregnancy, per pregnancy, than women without IBD (odds
ratio [OR], 1.23; 95% confidence interval [CI], 1.01-1.49), whereas women with UC
did not (OR, 0.98; 95% CI, 0.80-1.20). In pregnancies of women with CD and UC who
underwent IBD-related surgery before pregnancy, there was a nonsignificant
increase in risk of ectopic pregnancy compared with pregnancies in women with IBD
who did not have surgery (OR, 1.49; 95% CI, 0.91-2.44 for CD, and OR, 1.17; 95%
CI, 0.54-2.52 for UC). CONCLUSIONS: We found a statistically significant
increased risk of ectopic pregnancy in pregnancies of women with CD compared with
pregnancies of women without IBD. Surgery for IBD before pregnancy increased the
risk of ectopic pregnancy, although this increase was not statistically
significant.
PMID- 28694134
TI - Hashimoto's encephalopathy and anti-MOG antibody encephalitis: 50 years after
Lord Brain's description.
AB - PURPOSE: To consider the role of anti-MOG Abs associated encephalitis in
Hashimoto's Encephalitis (HE). RESULTS: A 10 year old girl with pre-existing
Hashimoto's thyroiditis presented with dysarthria, ataxia and lethargy whilst
euthyroid. Brain MRI showed multifocal T2 and FLAIR hyperintense lesions. She
responded promptly to treatment with corticosteroids. Her clinical scenario was
comparable to a sizeable minority of patients diagnosed with HE in the
literature, who have similar brain MRIs. Serum was positive for anti-myelin
oligodendrocyte glycoprotein (MOG) Ab, implicating this antibody-mediated process
in this patient's illness. CONCLUSION: We hypothesize that anti-MOG Ab associated
demyelination may underlie a subset of patients with HE.
PMID- 28694136
TI - Iatrogenic aortic dissection in a preterm neonate presenting as acute renal
failure.
PMID- 28694135
TI - Characteristics of pediatric multiple sclerosis: The Turkish pediatric multiple
sclerosis database.
AB - OBJECTIVE: To document the clinical and paraclinical features of pediatric
multiple sclerosis (MS) in Turkey. METHODS: Data of MS patients with onset before
age 18 years (n = 193) were collected from 27 pediatric neurology centers
throughout Turkey. Earlier-onset (<12 years) and later-onset (>=12 years) groups
were compared. RESULTS: There were 123 (63.7%) girls and 70 (36.3%) boys aged 4
17 years, median 14 years at disease onset. Family history of MS was 6.5%. The
first presentation was polysymptomatic in 55.4% of patients, with brainstem
syndromes (50.3%), sensory disturbances (44%), motor symptoms (33.2%), and optic
neuritis (26.4%) as common initial manifestations. Nineteen children had facial
paralysis and 10 had epileptic seizures at first attack; 21 (11%) were initially
diagnosed with acute disseminated encephalomyelitis (ADEM). Oligoclonal bands
were identified in 68% of patients. Magnetic resonance imaging revealed
periventricular (96%), cortical/juxtacortical (64.2%), brainstem (63%),
cerebellum (51.4%), and spinal cord (67%) involvement. Visual evoked potentials
(VEP) were abnormal in 52%; serum 25-hydroxyvitamin D levels were low in 68.5% of
patients. The earlier-onset group had a higher rate of infection/vaccination
preceding initial attack, initial diagnosis of ADEM, longer interval between
first 2 attacks, and more disability accumulating in the first 3 years of the
disease. CONCLUSION: Brainstem and cerebellum are common sites of clinical and
radiological involvement in pediatric-onset MS. VEP abnormalities are frequent
even in patients without history of optic neuropathy. Vitamin D status does not
appear to affect the course in early disease. MS beginning before 12 years of age
has certain characteristics in history and course.
PMID- 28694137
TI - Idiopathic T cell lymphopenia identified in New York State Newborn Screening.
AB - Quantification of T-cell receptor excision circles (TRECs) for newborn screening
for SCID has advanced the diagnosis of severe combined immune deficiency (SCID).
However, it has led to the identification of infants with T cell lymphopenia
without known cause. The clinical characteristics, appropriate laboratory
monitoring, and outcomes of patients remain unclear. We performed a retrospective
review of clinical and laboratory studies for 26 infants collected from 7 New
York State referral centers from 2010 to 2016 with low TRECs (mean, 70copies/MUl)
and subnormal CD3 counts (mean, 1150/cubicmm). Over time absolute CD3 counts
increased in 17 and decreased in 9; 22 (85%) have done well clinically regardless
of absolute T cell values. Additional infants with TCL will continue to be
identified in newborn screening panels. While most patients seem to do well
clinically, parameters for diagnosis and monitoring have yet to be formalized,
and additional information needs to be collected, causes and outcomes reported.
PMID- 28694138
TI - Does type-I interferon drive systemic autoimmunity?
AB - Type-I interferon (IFN)-mediated immune response involves both innate and
adaptive immune system and has a pivotal role in antiviral defence. A complex
interplay of intracellular signaling pathways and tight regulatory systems drive
the IFN activation. The observation of an aberrant stimulation of this system as
a common molecular basis in peculiar inherited autoimmune and autoinflammatory
disorders led to the concept of "type I interferonopathies". But the precise
genetic dissection of this growing spectrum of diseases adds more and more
complexity to the comprehension of this concept and a lot of unsolved questions
remain such as how type I IFN can drive systemic inflammation in these clinically
and genetically heterogeneous diseases.
PMID- 28694139
TI - Systematic review and meta-analysis of the nitrate reductase assay for drug
susceptibility testing of Mycobacterium tuberculosis and the detection limits in
liquid medium.
AB - Recently, the need for rapid, reliable, and low-cost drug susceptibility testing
(DST) methods has increased due to the emergence of multidrug-resistant
Mycobacterium tuberculosis. Colorimetric methods of DST provide results more
quickly than standard culture methods and are inexpensive than molecular methods.
Thus, colorimetric methods, such as the nitrate reductase assay (NRA), are being
recommended. We searched Medline PubMed for reports on the NRA for DST of M.
tuberculosis written in English and published within the last five years. We
selected 20 reports on six major anti-TB drugs and conducted a meta-analysis
using Meta-Disc software. The pooled sensitivities for isoniazid, rifampicin,
streptomycin, ethambutol, ofloxacin, and kanamycin were 95.4%, 96.4%, 91.5%,
93.1%, 99.3%, and 88.4%, and the pooled specificities were 98.5%, 99.2%, 92.9%,
97.8%, 97.4%, and 99.4%, respectively. The area under the summary receiver
operator curve for all drugs was 0.9723-0.9952. The time to results (TTR) for the
direct and indirect NRAs was 7-28days and 6-15days, respectively. Quality
assessments were conducted using the quality of diagnostic accuracy studies tool
(QUADAS-2) items, and most reports showed good performance. However, ethambutol,
streptomycin, and kanamycin showed relatively low sensitivity. We performed a
quantitative NRA in liquid media at various inoculum concentrations. The TTR at
4.94*106, 1.67*104, and 2.27*102CFU/mL was 4, 14, and 14days, respectively. The
minimum absorbance and nitrite concentration for positive samples were 0.8 and
168MUM, respectively. We propose a quantitative standard to determine sample
positivity to address the problems with the current standard NRA which is much
less expensive than the conventional assay conducted on solid medium.
PMID- 28694140
TI - miRNAs in B Cell Development and Lymphomagenesis.
AB - B lymphocytes are essential for an efficient immune response against a variety of
pathogens. A large fraction of hematologic malignancies is of B cell origin,
suggesting that the development and activation of B cells need to be tightly
regulated. In recent years, increasing evidence has emerged demonstrating that
microRNAs (miRNAs) - a class of non-coding RNAs that control gene expression -
are involved in the regulation of B cell development and function. We provide
here an overview of the current knowledge on the role of miRNAs and their
relevant targets in B cell development, B cell activation, and B cell malignant
transformation.
PMID- 28694141
TI - Amylin Receptor: A Potential Therapeutic Target for Alzheimer's Disease.
AB - Alzheimer'sdisease (AD) is a progressive neurodegenerative disorder,
characterized by senile plaques constituting extracellular deposits of beta
amyloid (Abeta) fibrils. Since Abeta accumulation in the brain is considered an
early event preceding, by decades, cognitive dysfunction, disease-modifying
treatments are aimed at facilitating clearance of this protein from the brain or
ameliorating its toxic effects. Recent studies have identified the amylin
receptor as a capable mediator of the deleterious actions of Abeta and
furthermore, administration of amylin receptor-based peptides has been shown to
improve spatial memory and learning in transgenic mouse models of AD. Here, by
discussing available evidence, we posit that the amylin receptor could be
considered a potential therapeutic target for AD, and present the rationale for
using amylin receptor antagonists to treat this debilitating condition.
PMID- 28694142
TI - Increased PSA expression on prostate cancer exosomes in in vitro condition and in
cancer patients.
AB - Prostate specific antigen (PSA) test is the most common, clinically validated
test for the diagnosis of prostate cancer (PCa). While neoplastic lesions of the
prostate may cause aberrant levels of PSA in the blood, the quantitation of free
or complexed PSA poorly discriminates cancer patients from those developing
benign lesions, often leading to invasive and unnecessary surgical procedures.
Microenvironmental acidity increases exosome release by cancer cells. In this
study we evaluated whether acidity, a critical phenotype of malignancy, could
influence exosome release and increase the PSA expression in nanovesicles
released by PCa cells. To this aim, we exploited Nanoparticle Tracking Analysis
(NTA), an immunocapture-based ELISA, and nanoscale flow-cytometry. The results
show that microenvironmental acidity induces an increased release of nanovesicles
expressing both PSA and the exosome marker CD81. In order to verify whether the
changes induced by the local selective pressure of extracellular acidity may
correspond to a clinical pathway we used the same approach to evaluate the levels
of PSA-expressing exosomes in the plasma of PCa patients and controls, including
subjects with benign prostatic hypertrophy (BPH). The results show that only PCa
patients have high levels of nanovesicles expressing both CD81 and PSA. This
study shows that tumor acidity exerts a selective pressure leading to the release
of extracellular vesicles that express both PSA and exosome markers. A comparable
scenario was shown in the plasma of prostate cancer patients as compared to both
BPH and healthy controls. These results suggest that microenvironmental acidity
may represent a key factor which determines qualitatively and quantitatively the
release of extracellular vesicles by malignant tumors, including prostate cancer.
This condition leads to the spill-over of nanovesicles into the peripheral blood
of prostate cancer patients, where the levels of tumor biomarkers expressed by
exosomes, such as PSA-exosomes, may represent a novel, non-invasive clinical tool
for the screening and early diagnosis of prostate cancer.
PMID- 28694143
TI - Assessing drug causality: It is time to become European!
PMID- 28694144
TI - AT2 receptors in cardiovascular and renal diseases.
AB - The renin-angiotensin system (RAS) plays an important role in the initiation and
progression of cardiovascular and renal diseases. These actions mediated by AT1
receptor (AT1R) are well established and led to development of selective AT1R
blockers (ARBs). In contrast, there is scientific evidence that AT2 receptor
(AT2R) mediates effects different from and often opposing those of the AT1R.
Meagrely expressed in healthy tissue the AT2R is upregulated in injuries
providing an endogenous protection to inflammatory, oxidative and apoptotic
processes. Interestingly the beneficial effects mediated by AT2R can be further
enhanced by pharmacological intervention using the recently developed AT2R
agonists. This review article summarizes our current knowledge about regulation,
signalling and effects mediated by AT2R in health and disease, with emphasis on
cardiac and renal systems. At the end a novel concept of natural protective
systems will be introduced and discussed as an attractive target in drug
development.
PMID- 28694145
TI - Sex and gender landscape in pharmacology.
PMID- 28694146
TI - Can causality assessment fulfill the new European definition of adverse drug
reaction? A review of methods used in spontaneous reporting.
AB - Causality assessment is a fundamental biomedical technique for the signal
detection performed by Pharmacovigilance centers in a Spontaneous reporting
system. Moreover, it is a crucial and important practice for detecting
preventable adverse drug reactions. Among different methods for causality
assessment, algorithms (such as the Naranjo, or Begaud Methods) seem for their
operational procedure and easier applicability one of the most commonly used
methods. With the upcoming of the new European Pharmacovigilance legislation
including in the definition of the adverse event also effects resulting from
abuse, misuse and medication error, all well-known preventable causes of ADRs,
there was an emerging need to evaluate whether algorithms could fulfill this new
definition. In this review, twenty-two algorithmic methods were identified and
none of them seemed to fulfill perfectly the new criteria of adverse event
although some of them come close. In fact, several issues were arisen in applying
causality assessment algorithms to these new definitions as for example the
impossibility to answer the rechallenge question in case of medication error or
AEFI (Adverse Event Following Immunization). Moreover, the exact conditions at
which events occurred, as for example dosage or mode of administration should be
considered to better assess causality in conditions of abuse/overdose, or misuse
as well as in conditions of lack of expected efficacy reports for
biotechnological drugs and adverse event occurring after mixing of vaccines.
Therefore, this review highlights the need of updating algorithmic methods to
allow a perfect applicability in all possible clinical scenarios accordingly or
not with the terms of marketing authorization.
PMID- 28694147
TI - Predictive and Prognostic Value of Preoperative Thrombocytosis in Upper Tract
Urothelial Carcinoma.
AB - PURPOSE: The purpose of this study was to evaluate the predictive and prognostic
role of preoperative thrombocytosis (TC) in upper tract urothelial carcinoma
(UTUC) after radical nephroureterectomy (RNU) in a large multi-institutional
cohort of patients. METHODS: Records of 2492 patients undergoing RNU for non
metastatic UTUC between 1990 and 2008 were retrospectively analyzed. Preoperative
TC was defined as a platelet count > 400 * 109/L, irrespective of gender type.
Logistic regression analyses were performed to evaluate its association with
pathologic features. Cox proportional hazards regression was used for estimation
of recurrence-free survival, cancer-specific survival, and overall survival.
RESULTS: Preoperative TC was found in 309 (12.4%) patients and was associated
with advanced tumor stage and grade, lymph node metastasis, lymphovascular
invasion, tumor architecture, necrosis, and concomitant carcinoma in situ (P
values <= .027). Preoperative TC independently predicted >= pT2 (P < .001), non
organ-confined (P < .001), and lymph node-positive (P < .001) disease in a
preoperative model that adjusted for the effects of age, gender, location,
multifocality, and tumor architecture. Within a median follow-up of 45 months,
recurrence occurred in 663 (26.6%) patients with 545 (21.9%) dying of UTUC. In
univariable Cox proportional hazard regression analysis, TC was significantly
associated with recurrence-free survival (hazard ratio [HR], 1.32; P = .015) and
overall survival (HR, 1.4; P < .001), but not cancer-specific survival (HR, 1.17;
P = .2). In both pre- and postoperative multivariable models, when adjusted for
the effects of standard clinicopathologic features, TC did not retain its
association with survival outcomes. CONCLUSIONS: Preoperative TC is associated
with adverse clinicopathologic features and predicts worse pathology at RNU.
Among other serum biomarkers, TC could benefit preoperative risk stratification
and help guide treatment decisions.
PMID- 28694148
TI - Intensity Dependence of Auditory Evoked Potentials in Primary Dysmenorrhea.
AB - : Some studies suggest that women with primary dysmenorrhea have distinct
emotional or personality features. For example, they might exaggerate their
responses to external stimuli, such as to intensity-increasing auditory stimuli.
Fifteen women with primary dysmenorrhea and 15 healthy women were invited to
undergo tests of the intensity dependence of auditory evoked potentials (IDAEP),
the Functional and Emotional Measure of Dysmenorrhea, and the Plutchik-van Praag
Depression Inventory. Study participants with dysmenorrhea showed higher
Functional and Emotional scale scores and stronger IDAEP. Regarding the IDAEP
generation, the source inversion of N1 and P2 disclosed the activated bilateral
superior temporal gyri, medial and superior prefrontal gyri in all participants,
and additionally, the middle frontal gyri in dysmenorrhea patients. We report a
pronounced IDAEP in primary dysmenorrhea, which indicates the decreased cerebral
serotonergic innervations and points to increased activations in the prefrontal
and frontal areas in the disorder. PERSPECTIVE: Using an IDAEP technique, the
authors found decreased serotonergic innervation and altered cerebral activation
in women with primary dysmenorrhea, which might offer some pharmacotherapeutic
clues for the disorder.
PMID- 28694149
TI - Host regulation by the ectophagous parasitoid wasp Bracon nigricans.
AB - The host regulation process has been widely investigated in endophagous
parasitoid wasps, which in most cases finely interact with living hosts (i.e.
koinobiont parasitoids). In contrast, only very limited information is available
for ectophagous parasitoids that permanently paralyze and rapidly suppress their
victims (i.e. idiobiont parasitoids). Here we try to fill this research gap by
investigating the host regulation by Bracon nigricans, an ectophagous idiobiont
wasp species. Parasitism, mainly by venom action, is able to redirect host
metabolism in order to enhance its nutritional suitability for the developing
parasitoid larvae and to provide the required metabolic support to host tissues.
The observed alterations of the host titers of haemolymph proteins, carbohydrates
and acylglycerols are associated with a parasitoid-induced mobilization of
nutrients stored in the fat body. This tissue undergoes a controlled degradation
mediated by a close surface interaction with haemocytes, where a cathepsin L
activity is localized, as demonstrated by immunolocalization, biochemical and
transcriptional data. B. nigricans parasitism does not markedly influence the
survival of haemocytes, even though a persistent suppression of the immune
competence is observed in parasitized hosts, which show a reduced capacity to
encapsulate and melanize non-self objects. These immune alterations likely allow
a more efficient food uptake and use by the ectophagous larvae. The obtained
results indicate that the host regulation process in basal lineages of parasitic
Hymenoptera is more complex than expected and shares functional similarities with
adaptive strategies occurring in derived koinobiont species.
PMID- 28694150
TI - The development of a retroperitoneal dissection model.
AB - Knowledge of ureteric anatomy is essential for ureteric injury prevention in
laparoscopic gynecologic surgery. Rates of injury increase with limited surgical
experience and reduced surgical volume. Currently, there are no low-fidelity or
high-fidelity simulation models for teaching and practicing ureteric dissection.
Our goal was to design a laparoscopic simulation model for retroperitoneal
anatomy with high face validity that is low-cost and easily reproducible. A low
fidelity 3-dimensional simulation model was developed that represents key
anatomic structures encountered during retroperitoneal dissection and ureteric
identification. Materials, construction steps, and costs were determined. The
models were trialed by expert laparoscopic surgeons. Demographic information that
included age, gender, surgical experience, and complex laparoscopic case volumes
was collected. Face validity was assessed with a 5-item Likert-scale. The total
cost of 1 model ranged from $65 to $75. The majority of the materials that were
used were reusable, except for 2 components that cost <$1 per use. Seven expert
surgeons participated in the study, all of whom were fellowship-trained minimally
invasive gynecologic surgeons or currently enrolled in this type of fellowship
program. Participants agreed or strongly agreed that the model resembled the
texture of the ureter, vessels, and peritoneal layer (n=6; 86%), approximated the
correct anatomic course of the ureter (n=7; 100%), and closely approximated live
surgery (n=5; 71%). They also agreed or strongly agreed that the model would be
useful for teaching laparoscopic retroperitoneal dissection (n=7; 100%), for
assessing a learner's ability before performing in the operating room (n=6; 86%),
was low-cost (n=7; 100%), and was easily reproducible (n=6; 86%). This unique
model fills a gap in laparoscopic simulation training. No other low- or high
fidelity models for laparoscopic retroperitoneal ureteric dissection have been
identified in the literature. This simulation model is low-cost, easily
reproducible, closely resembles retroperitoneal dissection during laparoscopic
gynecologic surgery, and can be used for education and assessment.
PMID- 28694151
TI - Liposomal bupivacaine decreases pain following retropubic sling placement: a
randomized placebo-controlled trial.
AB - BACKGROUND: Midurethral slings are commonly used to treat stress urinary
incontinence. Pain control, however, may be a concern. Liposomal bupivacaine is a
local anesthetic with slow release over 72 hours, demonstrated to lower pain
scores and decrease narcotic use postoperatively. OBJECTIVE: The purpose of this
study was to examine the impact of liposomal bupivacaine on pain scores and
narcotic consumption following retropubic midurethral sling placement. STUDY
DESIGN: This randomized, placebo-controlled trial enrolled women undergoing
retropubic midurethral sling procedures with or without concomitant anterior or
urethrocele repair. Subjects were allocated to receive liposomal bupivacaine
(intervention) or normal saline placebo injected into the trocar paths and
vaginal incision at the conclusion of the procedure. At the time of drug
administration, surgeons became unblinded, but did not collect outcome data.
Participants remained blinded to treatment. Surgical procedures and perioperative
care were standardized. The primary outcome was the visual analog scale pain
score 4 hours after discharge home. Secondary outcomes included narcotic
consumption, time to first bowel movement, and pain scores collected in the
mornings and evenings until postoperative day 6. The morning pain item assessed
"current level of pain"; the evening items queried "current level of pain," "most
intense pain today," "average pain today with activity," and "average pain today
with rest." Likert scales were used to measure satisfaction with pain control at
1- and 2-week postoperative intervals. Sample size calculation deemed 52 subjects
per arm necessary to detect a mean difference of 10 mm on a 100-mm visual analog
scale. To account for 10% drop out, 114 participants were needed. RESULTS: One
hundred fourteen women were enrolled. After 5 exclusions, 109 cases were
analyzed: 54 women received intervention, and 55 women received placebo. Mean
participant age was 52 years, and mean body mass index was 30.4 kg/m2. Surgical
and demographic characteristics were similar, except for a slightly higher body
mass index in the placebo group (31.6 vs 29.2 kg/m2; P=.050), and fewer placebo
arm subjects received midazolam during anesthesia induction (44 vs 52; P=.015).
For the primary outcome, pain score (millimeter) 4 hours after discharge home was
lower in the intervention group (3.5 vs 13.0 millimeters; P=.014). Pain scores
were also lower for subjects receiving liposomal bupivacaine at other time points
collected during the first three postoperative days. Furthermore, fewer subjects
in the intervention group consumed narcotic medication on postoperative day 2 (12
vs 27; P=.006). There was no difference in satisfaction with pain control between
groups. Side-effects experienced, rate of postoperative urinary retention, and
time to first bowel movement were similar between groups. Finally, no serious
adverse events were noted. CONCLUSION: Liposomal bupivacaine decreased
postoperative pain scores following retropubic midurethral sling placement,
though pain was low in both the intervention and placebo groups. Participants who
received liposomal bupivacaine were less likely to use narcotics on postoperative
day 2. For this common outpatient surgery, liposomal bupivacaine may be a
beneficial addition. Given the cost of this intervention, however, future cost
effective analyses may be useful.
PMID- 28694152
TI - Drug interactions between non-rifamycin antibiotics and hormonal contraception: a
systematic review.
AB - OBJECTIVE: The purpose of this study was to determine whether interactions
between non-rifamycin antibiotics and hormonal contraceptives result in decreased
effectiveness or increased toxicity of either therapy. STUDY DESIGN: We searched
MEDLINE, Embase, clinicaltrials.gov, and Cochrane libraries from database
inception through June 2016. We included trials, cohort, case-control, and
pharmacokinetic studies in any language that addressed pregnancy rates,
pharmacodynamics, or pharmacokinetic outcomes when any hormonal contraceptive and
non-rifamycin antibiotic were administered together vs apart. Of 7291 original
records that were identified, 29 met criteria for inclusion. STUDY APPRAISAL AND
SYNTHESIS METHODS: Two authors independently assessed study quality and risk of
bias using the United States Preventive Services Task Force evidence grading
system. Findings were tabulated by drug class. RESULTS: Study quality ranged from
good to poor and addressed only oral contraceptive pills, emergency contraception
pills, and the combined vaginal ring. Two studies demonstrated no difference in
pregnancy rates in women who used oral contraceptives with and without non
rifamycin antibiotics. No differences in ovulation suppression or breakthrough
bleeding were observed in any study that combined hormonal contraceptives with
any antibiotic. No significant decreases in any progestin pharmacokinetic
parameter occurred during co-administration with any antibiotic. Ethinyl
estradiol area under the curve decreased when administered with dirithromycin,
but no other drug. CONCLUSION: Evidence from clinical and pharmacokinetic
outcomes studies does not support the existence of drug interactions between
hormonal contraception and non-rifamycin antibiotics. Data are limited by low
quantity and quality for some drug classes. Most women can expect no reduction in
hormonal contraceptive effect with the concurrent use of non-rifamycin
antibiotics.
PMID- 28694153
TI - Caffeinated energy drink intake modulates motor circuits at rest, before and
after a movement.
AB - Energy drinks are thought to improve certain aspects of athletic and cognitive
performances. Moreover, less is understood about physiological mechanisms that
might underlie these effects. The aim of this study was to examine the influence
of sugar-free energy drink (SFED) ingestion on corticomotor excitability and
plasticity. Fourteen college students consumed a commercially available SFED or a
"dummy" drink. By using Transcranial magnetic Stimulation (TMS) we investigated
resting motor threshold (RMT), motor evoked potential (MEP) amplitude and
cortical silent period (CSP). Paired-pulse stimulation was used to assess short
interval intracortical inhibition (SICI) and intracortical facilitation (ICF).
Sensorimotor integration was investigated with the short- and long-afferent
inhibition paradigms (SAI and LAI). Cortical plasticity was studied with the
paired associative stimulation (PAS) paradigm. In addition, we examined the
effect of SFED on simple reaction time (RT), pre-movement facilitation and post
exercise facilitation (PEF). SFED consumption decreased ICF, shortened RT,
increased pre-movement facilitation and PEF of the motor evoked potentials. These
results demonstrate that SFED consumption induced a shorter RT that is paralleled
by changes in cortical excitability at rest, prior and after a non-fatiguing
muscle contraction. These acute changes in brain function might be of relevance
in understanding the mechanisms underlying the enhancement of psychomotor
performance.
PMID- 28694154
TI - Short photoperiod reverses obesity in Siberian hamsters via sympathetically
induced lipolysis and Browning in adipose tissue.
AB - Changes in photoperiod length are transduced into neuroendocrine signals by
melatonin (MEL) secreted by the pineal gland triggering seasonally adaptive
responses in many animal species. Siberian hamsters, transferred from a long-day
'summer-like' photoperiod (LD) to a short-day 'winter-like' photoperiod (SD),
exhibit a naturally-occurring reversal in obesity. Photoperiod-induced changes in
adiposity are mediated by the duration of MEL secretion and can be mimicked by
exogenously administered MEL into animals housed in LD. Evidence suggests that
MEL increases the sympathetic nervous system (SNS) drive to white adipose tissue
(WAT). Here, we investigated whether MEL-driven seasonally adaptive losses in
body fat are associated with WAT lipolysis and browning. Hamsters were
subcutaneously administered vehicle (LD+VEH) or 0.4mg/kg MEL (LD+MEL) daily for
10weeks while animals housed in SD served as a positive control. MEL and SD
exposure significantly decreased the retroperitoneal (RWAT), inguinal (IWAT),
epididymal (EWAT) WAT, food intake and caused testicular regression compared with
the LD+VEH group. MEL/SD induced lipolysis in the IWAT and EWAT, browning of the
RWAT, IWAT, and EWAT, and increased UCP1 expression in the IBAT. Additionally,
MEL/SD significantly increased the number of shared MEL receptor 1a and dopamine
beta-hydroxylase-immunoreactive neurons in discrete brain sites, notably the
paraventricular hypothalamic nucleus, dorsomedial hypothalamic nucleus, arcuate
nucleus, locus coeruleus and dorsal motor nucleus of vagus. Collectively, these
findings support our hypothesis that SD-exposed Siberian hamsters undergo
adaptive decreases in body adiposity due to SNS-stimulated lipid mobilization and
generalized WAT browning.
PMID- 28694156
TI - Sex and menstrual cycle influences on three aspects of attention.
AB - Sex differences and menstrual cycle influences have been investigated in a
variety of cognitive abilities, but results regarding attention are comparably
sparse. In the present study, 35 men and 32 naturally cycling women completed
three attention tasks, which are commonly used in neuropsychological assessment
situations. All participants completed two sessions, which were time-locked to
the follicular (low progesterone) and luteal cycle phase (high progesterone) in
women. The results reveal higher operation speed during sustained attention in
men, but no sex differences in selected and divided attention. Menstrual cycle
influences were observed on accuracy in all three tasks. During divided and
sustained attention, for which a male advantage was previously reported, accuracy
was higher during the early follicular compared to the mid-luteal cycle phase.
Furthermore, during selected and sustained attention the learning effect from the
first to the second test session was higher in women who started the experiment
in their luteal cycle phase. These results suggest a possible role of
progesterone in modulating the ability to focus on certain stimulus aspects,
while inhibiting others and to sustain attention over a longer period of time.
PMID- 28694155
TI - Denervation as a tool for testing sympathetic control of white adipose tissue.
AB - This review summarizes the evidence derived from studies utilizing denervation
procedures to demonstrate sympathetic control of white adipose tissue metabolism
and body fat mass. A majority of the work demonstrating neural control of white
fat was performed in the Bartness laboratory with Siberian hamsters as the
predominant experimental model. These animals experience dramatic changes in body
fat mass in response to changes in photoperiod, however, the mechanisms
identified in hamsters have been reproduced or further elucidated by experiments
with other animal models. Evidence for the role of sympathetic innervation
contributing to the control of white adipocyte lipolysis and preadipocyte
proliferation is summarized. In addition, evidence from denervation experiments
for neural communication between different white fat depots as well as for a
feedback control loop between sensory afferents from individual fat depots and
sympathetic efferents to the same or distant white fat depots is discussed.
PMID- 28694157
TI - How methamphetamine exposure during different neurodevelopmental stages affects
social behavior of adult rats?
AB - Social behavior involves complex of different forms of interactions between
individuals that is essential for healthy mental and physical development
throughout lifespan. Psychostimulants, including methamphetamine (MA), have
neurotoxic effect, especially, if they are targeting CNS during its critical
periods of development. The present study was aimed on evaluation of changes in
social interactions (SI) following scheduled prenatal/neonatal MA treatment in
combination with acute application in adulthood. Eight groups of male and eight
groups of female rats were tested in adulthood: rats, whose mothers were exposed
to MA (5mg/ml/kg) or saline (SA, 1ml/kg) during the first half of gestation (ED 1
11), the second half of gestation (ED 12-22) and neonatal period (PD 1-11). To do
this, we compared indirect neonatal applications via the exposed dams with group
of rat pups that received MA or SA directly through injections. In adulthood,
half animals from each group were injected with MA (1mg/kg), second half with
saline 45min prior to the Social Interaction Test. Females and males were
observed for social and nonsocial activities of two unfamiliar individuals of the
same sex and treatment in a familiar Open field arena. The present study
demonstrated that prenatal/neonatal MA exposure leads to decrease the time spent
in genital investigation, following and nonsocial activity. Acute dose of MA
leads to a decrease in all SI patterns and to an increase in nonsocial activities
relative to acute SA. Females were more active than males. Animals exposed to
prenatal/neonatal treatment during the second half of gestation (ED 12-22) and
throughout lactation period (PD 1-11 indirect/direct) had fewer SI and greater
exploratory behavior than animals exposed during the first half of gestation (ED
1-11).
PMID- 28694158
TI - Implication of the vagus nerve in breathing pattern during sequential swallowing
in rats.
AB - The ventilatory pattern during sequential swallowing is influenced by the vagal
activity. As the vagus nerve is paired and mixed, we aimed (1) to determine if
vagal implication in swallowing and breathing coordination is symmetric. (2) to
study the importance of vagal afferences in swallowing and breathing
coordination. Sixty two Wistar rats (7-11weeks, 260-400g) were studied by
barometric plethysmography. In the first part of the study, we determined the
effects of a right cervical vagotomy and the effects of a left cervical vagotomy
on ventilatory pattern at rest and during sequential swallowing (14 rats with
right vagotomy, 14 rats with left vagotomy and 14 rats with sham surgery).
Comparisons of ventilatory variables were made between right and left vagotomized
animals. Thereafter, we determined the effects of electrical vagus nerve
stimulation (VNS) on ventilatory pattern at rest and during sequential swallowing
(10 rats with electrical VNS and 10 rats with sham VNS). We showed that a right
or a left cervical vagotomy does not alter ventilation at rest, but induces
during sequential swallowing a decrease in respiratory rate (RR) (p<0.001) and
mean inspiratory flow (VT/TI) (p<0.01) compared to baseline. These modifications
were not observed following sham surgery and there were no differences in
ventilatory variables at rest and during sequential swallowing between right
vagotomized rats and left vagotomized rats (p>0.05). Electrical VNS had no effect
on ventilation at rest, but it minimized during sequential swallowing a decrease
in RR related to a local alteration of the vagus nerve after placement of the
electrodes as shown following sham VNS. In conclusion, the implication of vagus
nerve in breathing pattern during sequential swallowing seems symmetric and
influenced by activation of the vagal afferent pathway. These data can be useful
when testing electrical VNS in swallowing disorders.
PMID- 28694159
TI - Growing in Silence!
PMID- 28694160
TI - Artificial neural network based particle size prediction of polymeric
nanoparticles.
AB - Particle size of nanoparticles and the respective polydispersity are key factors
influencing their biopharmaceutical behavior in a large variety of therapeutic
applications. Predicting these attributes would skip many preliminary studies
usually required to optimize formulations. The aim was to build a mathematical
model capable of predicting the particle size of polymeric nanoparticles produced
by a pharmaceutical polymer of choice. Polymer properties controlling the
particle size were identified as molecular weight, hydrophobicity and surface
activity, and were quantified by measuring polymer viscosity, contact angle and
interfacial tension, respectively. A model was built using artificial neural
network including these properties as input with particle size and polydispersity
index as output. The established model successfully predicted particle size of
nanoparticles covering a range of 70-400nm prepared from other polymers. The
percentage bias for particle prediction was 2%, 4% and 6%, for the training,
validation and testing data, respectively. Polymer surface activity was found to
have the highest impact on the particle size followed by viscosity and finally
hydrophobicity. Results of this study successfully highlighted polymer properties
affecting particle size and confirmed the usefulness of artificial neural
networks in predicting the particle size and polydispersity of polymeric
nanoparticles.
PMID- 28694161
TI - CXCR4 targeted dendrimer for anti-cancer drug delivery and breast cancer cell
migration inhibition.
AB - CXCR4 and its ligand CXCL12 play a critical role in the metastasis of various
types of cancer including breast cancer. Breast tumors preferentially metastasize
to the lung, bones and distant lymph nodes, secreting high levels of CXCL12. We
hypothesized that targeted inhibition of CXCR4 in breast cancer cells should
suppress CXCR4-positive tumor cells toward secondary metastatic sites. In the
present study, the efficacy of CXCR4 targeted dendrimers carrying DOX (LFC131-DOX
D4) on cellular binding, cytotoxicity, and migration of BT-549-Luc and T47D
breast cancer cells was investigated. PAMAM dendrimers encapsulating DOX was
surface functionalized with LFC131 peptide which recognized CXCR4 expressed on
the surface of breast cancer cells. The LFC131-DOX-D4 bound to breast cancer
cells resulting in significantly enhanced in vitro cellular toxicity as compared
with non-targeted dendrimers. The LFC131-D4 exhibited remarkable reduced
migration of BT-549-Luc breast cancer cells toward chemoattractant. This report
demonstrated the potential utility of LFC131-dendrimer conjugates for breast
cancer therapy and metastasis.
PMID- 28694162
TI - Impaired bone strength estimates at the distal tibia and its determinants in
adolescents with anorexia nervosa.
AB - BACKGROUND: Altered bone microarchitecture and higher marrow adipose tissue (MAT)
may reduce bone strength. High resolution pQCT (HRpQCT) allows assessment of
volumetric BMD (vBMD), and size and microarchitecture parameters of bone, while
1H-magnetic resonance spectroscopy (1H-MRS) allows MAT evaluation. We have
reported impaired microarchitecture at the non-weight bearing radius in
adolescents with anorexia nervosa (AN) and that these changes may precede aBMD
deficits. Data are lacking regarding effects of AN on microarchitecture and
strength at the weight-bearing tibia in adolescents and young adults, and the
impact of changes in microarchitecture and MAT on strength estimates. OBJECTIVE:
To compare strength estimates at the distal tibia in adolescents/young adults
with AN and controls in relation to vBMD, bone size and microarchitecture, and
spine MAT. DESIGN AND METHODS: This was a cross-sectional study of 47
adolescents/young adults with AN and 55 controls 14-24years old that assessed
aBMD and body composition using DXA, and distal tibia vBMD, size,
microarchitecture and strength estimates using HRpQCT, extended cortical
analysis, individual trabecular segmentation, and finite element analysis. Lumbar
spine MAT (1H-MRS) was assessed in a subset of 19 AN and 22 controls. RESULTS:
Areal BMD Z-scores were lower in AN than controls. At the tibia, AN had greater
cortical porosity, lower total and cortical vBMD, cortical area and thickness,
trabecular number, and strength estimates than controls. Within AN, strength
estimates were positively associated with lean mass, aBMD, vBMD, bone size and
microarchitectural parameters. MAT was higher in AN, and associated inversely
with strength estimates. CONCLUSIONS: Adolescents/young adults with AN have
impaired microarchitecture at the weight-bearing tibia and higher spine MAT,
associated with reduced bone strength.
PMID- 28694163
TI - Mice maintain predominantly maternal Galphas expression throughout life in brown
fat tissue (BAT), but not other tissues.
AB - The murine Gnas (human GNAS) locus gives rise to Galphas and different splice
variants thereof. The Galphas promoter is not methylated thus allowing biallelic
expression in most tissues. In contrast, the alternative first Gnas/GNAS exons
and their promoters undergo parent specific methylation, which limits
transcription to the non-methylated allele. Pseudohypoparathyroidism type Ia
(PHP1A) or type Ib (PHP1B) are caused by heterozygous maternal GNAS mutations
suggesting that little or no Galphas is derived in some tissues from the non
mutated paternal GNAS thereby causing hormonal resistance. Previous data had
indicated that Galphas is mainly derived from the maternal Gnas allele in brown
adipose tissue (BAT) of newborn mice, yet it is biallelically expressed in adult
BAT. This suggested that paternal Galphas expression is regulated by an unknown
factor(s) that varies considerably with age. To extend these findings, we now
used a strain-specific SNP in Gnas exon 11 (rs13460569) for evaluation of parent
specific Galphas expression through the densitometric quantification of BanII
digested RT-PCR products and digital droplet PCR (ddPCR). At all investigated
ages, Galphas transcripts were derived in BAT predominantly from the maternal
Gnas allele, while kidney and liver showed largely biallelic Galphas expression.
Only low or undetectable levels of other paternally Gnas-derived transcripts were
observed, making it unlikely that these are involved in regulating paternal
Galphas expression. Our findings suggest that a cis-acting factor could be
implicated in reducing paternal Galphas expression in BAT and presumably in
proximal renal tubules, thereby causing PTH-resistance if the maternal GNAS/Gnas
allele is mutated.
PMID- 28694164
TI - A homologue of Nr5a1 activates cyp19a1a transcription additively with Nr5a2 in
ovarian follicular cells of the orange-spotted grouper.
AB - Transcription factors of nuclear receptor 5A (Nr5a) subfamily play pivotal roles
in regulation of steroidogenic enzymes in vertebrates including teleosts. In the
orange-spotted grouper, the expression of Nr5a1a was only detectable in the
ovary, spleen, and head kidney in the female. The immunoreactive Nr5a1a was
present in ovarian follicular and germ cells. In the ovarian follicular cells
surrounding vitellogenic oocytes, Nr5a1a was detected both in the nucleus and
cytoplasm, and co-localized with Cyp19a1a and Nr5a2. In the ovarian follicular
cells surrounding fully grown oocytes, Nr5a1a was localized almost exclusively to
the cytoplasm together with Nr5a2. Nr5a1a could up-regulate cyp19a1a promoter
activities through Nr5a sites, and further increase the responses elicited by
Nr5a2 at sub-maximal doses. Chromatin immunoprecipitation analysis showed that
Nr5a1a bound to cyp19a1a promoter in the vitellogenic but not fully grown ovary.
Taken together, Nr5a1a up-regulates cyp19a1a additively with Nr5a2 during
vitellogenesis, and its cytoplasmic sequestration may also contribute to the down
regulation of cyp19a1a in the fully grown ovary.
PMID- 28694165
TI - Reasons why women have induced abortions: a synthesis of findings from 14
countries.
AB - OBJECTIVE: Many reasons inform women's reproductive decision-making. This paper
aims to present the reasons women give for obtaining induced abortions in 14
countries. STUDY DESIGN: We examined nationally representative data from 14
countries collected in official statistics, population-based surveys, and
facility-based surveys of abortion patients. In each country, we calculated the
percentage distribution of women who have abortions by main reason given for the
abortion. We examined these reasons across countries and within countries by
women's sociodemographic characteristics (age, marital status, educational
attainment, and residence). Where data are available, we also studied the
multiple reasons women give for having an abortion. RESULTS: In most countries,
the most frequently cited reasons for having an abortion were socioeconomic
concerns or limiting childbearing. With some exceptions, little variation existed
in the reasons given by women's sociodemographic characteristics. Data from three
countries where multiple reasons could be reported in the survey showed that
women often have more than one reason for having an abortion. CONCLUSION: This
study shows that women have abortions for a variety of reasons, and provides a
broad picture of the circumstances that inform women's decisions to have
abortions. IMPLICATIONS: Future research should examine in greater depth the
personal, social, economic, and health factors that inform a woman's decision to
have an abortion as these reasons may shed light on the potential consequences
that unintended births can have on women's lives.
PMID- 28694166
TI - Initial Accuracy of and Learning Curve for Transvaginal Ultrasound with Bowel
Preparation for Deep Endometriosis in a US Tertiary Care Center.
AB - STUDY OBJECTIVE: To evaluate the diagnostic accuracy and learning curve of a
sonographic mapping protocol for deep endometriosis (DE). DESIGN: Retrospective
cohort study (Canadian Task Force classification II-3). SETTING: Tertiary
referral center in the United States. PATIENTS: 117 consecutive patients who
presented to our gynecology clinic with complaints of significant noncyclic
pelvic pain of at least 6 months' duration, and/or clinical findings concerning
for deep endometriosis and who were referred for transvaginal ultrasound with
bowel preparation. INTERVENTIONS: Patients underwent transvaginal ultrasound with
bowel-preparation (TVUS-BP) performed by a single radiologist. Findings
suspicious for DE were reported and correlated with surgical and
histopathological findings. The duration of the examination and number of cases
required to achieve proficiency were calculated for positive, equivocal, and
negative findings. MEASUREMENTS AND MAIN RESULTS: Among 117 patients (median age,
35 years; range, 19-54 years) referred for TVUS-BP, 113 had complete
examinations. Fifty-seven of these 113 patients underwent surgical exploration
within 1 year, and DE was identified surgically in 23 of them. DE of the
rectosigmoid colon and/or rectovaginal septum was detected with a sensitivity of
94% (95% confidence interval [CI], 70%-100%) and specificity of 100% (95% CI, 91%
100%). DE of the retrocervical region and/or uterosacral ligaments was detected
with a sensitivity of 86% (95% CI, 65%-97%) and specificity of 94% (95% CI, 81%
99%). Proficiency, defined by a flattening of the learning curve, was achieved
after 70 to 75 scans. The mean duration of the examination was 42 +/- 4 minutes
initially, but declined to 15 +/- 4 minutes once proficiency was achieved. Cases
of equivocal or minimal disease demonstrated the greatest decline in examination
duration. CONCLUSION: A newly applied TVUS-BP protocol for detection of pelvic DE
is highly accurate and required only a modest learning curve to achieve
procedural proficiency in a US tertiary referral center where physicians
interpret but typically do not perform TVUS exams. Overcoming diagnostic
uncertainty regarding minimal or equivocal disease appeared to be an important
factor in the initial learning curve. With adequate training, TVUS-BP may be
adapted as a primary diagnostic tool for detecting pelvic DE.
PMID- 28694167
TI - Minimally Invasive Surgery Survey: A Survey of Surgical Team Members' Perceptions
for Successful Minimally Invasive Surgery.
AB - STUDY OBJECTIVE: To develop a valid and reliable survey to measure surgical team
members' perceptions regarding their institution's requirements for successful
minimally invasive surgery (MIS). DESIGN: Questionnaire development and
validation study (Canadian Task Force classification II-2). SETTING: Three
hospital types: rural, urban/academic, and community/academic. PARTICIPANTS:
Minimally invasive staff (team members). INTERVENTION: Development and validation
of a minimally invasive surgery survey (MISS). MEASUREMENT AND MAIN RESULTS:
Using the Safety Attitudes questionnaire as a guide, we developed questions
assessing study participants' attitudes regarding the requirements for successful
MIS. The questions were closed-ended and responses based on a 5-point Likert
scale. The large pool of questions was then given to 4 focus groups made up of 3
to 6 individuals. Each focus group consisted of individuals from a specific
profession (e.g., surgeons, anesthesiologists, nurses, and surgical technicians).
Questions were revised based on focus group recommendations, resulting in a final
52-question set. The question set was then distributed to MIS team members.
Individuals were included if they had participated in >10 MIS cases and worked in
the MIS setting in the past 3 months. Participants in the trial population were
asked to repeat the questionnaire 4 weeks later to evaluate internal consistency.
Participants' demographics, including age, gender, specialty, profession, and
years of experience, were captured in the questionnaire. Factor analysis with
varimax rotation was performed to determine domains (questions evaluating similar
themes). For internal consistency and reliability, domains were tested using
interitem correlations and Cronbach's alpha. Cronbach's alpha > .6 was considered
internally consistent. Kendall's correlation coefficient tau closer to 1 and with
p < .05 was considered significant for the test-retest reliability. Two hundred
fifty participants answered the initial question set. Of those, 53 were
eliminated because they did not meet inclusion criteria or failed to answer all
questions, leaving 197 participants. Most participants were women (68% vs 32%),
and 42% were between the ages 30 and 39 years. Factor analysis identified 6
domains: collaboration, error reporting, job proficiency/efficiency, problem
solving, job satisfaction, and situational awareness. Interitem correlations
testing for redundancy for each domain ranged from .2 to .7, suggesting similar
themed questions while avoiding redundancy. Cronbach's alpha, testing internal
consistency, was .87. Sixty-two participants from the original cohort repeated
the question set at 4 weeks. Forty-three were analyzed for test-retest
reliability after excluding those who did not meet inclusion criteria. The final
questions showed high test-retest reliability (tau = .3-.7, p < .05). The final
questionnaire was made up of 29 questions from the original 52 question set.
CONCLUSION: The MISS is a reliable and valid tool that can be used to measure how
surgical team members conceptualize the requirements for successful MIS. The MISS
revealed that participants identified 6 important domains of a successful
workenvironment: collaboration, error reporting, job proficiency/efficiency,
problem-solving, job satisfaction, and situational awareness. The questionnaire
can be used to understand and align various surgical team members' goals and
expectations and may help improve quality of care in the MIS setting.
PMID- 28694168
TI - Characterizing porcine invariant natural killer T cells: A comparative study with
NK cells and T cells.
AB - CD1d-restricted invariant natural killer T (iNKT) cells are innate-like T cells
that share phenotypic characteristics of both NK and conventional T cells
(Tconv). Although iNKT cells have been well characterized in mice and humans,
functional CD1d and CD1d-restricted iNKT cells are not universally expressed in
mammals. Swine express iNKT cells that can be detected using alpha
galactosylceramide (alpha-GalCer)-loaded CD1d tetramers. In the present study, we
characterized iNKT cells from the blood, spleen, lymph node, lung and liver of
commercial mixed-breed pigs, and compared their phenotype to NK cells and Tconv.
The principal findings are that pig iNKT cells are CD8alpha and CD44 positive and
CD11b and Nkp46 negative. Most are also negative for the CD4 co-receptor, which
is used to distinguish functionally distinct mouse and human iNKT cells subsets.
The frequency of IFN-gamma-producing CD8alphabright iNKT cells was 3-4-fold
higher than CD8alphadull iNKT cells, suggesting that CD8alpha expression
identifies iNKT cells with a unique functional role in immune responses. Finally,
large variability was detected among pigs in interactions between iNKT cells and
monocytes when iNKT cells were activated with alpha-GalCer, which raises a
cautionary note about manipulating iNKT cells for immunotherapy. Collectively,
our study provides important phenotypic and functional information about porcine
iNKT cells that will be useful for understanding how iNKT cells contribute to
immune responses in swine, with potential implications for human health.
PMID- 28694169
TI - Differential expression and functional roles of chemokine (C-C motif) ligand 23
and its receptor chemokine (C-C motif) receptor type 1 in the uterine endometrium
during early pregnancy in pigs.
AB - Many chemokines expressed by cells of the uterine endometrium of mammals are
involved in cell-cell interactions. However, little is known about expression and
functional roles of chemokine (C-C motif) ligand 23 (CCL23) in the uterine
endometrium. Results of this study demonstrated that CCL23 and its receptor,
chemokine (C-C motif) receptor type 1 (CCR1), are up-regulated in porcine
endometria during pregnancy. CCL23 and CCR1 mRNAs were strongly expressed in
endometrial glandular (GE) and luminal (LE) epithelial cells. Treatment of
porcine uterine luminal epithelial (pLE) cells with recombinant CCL23 increased
the abundances of PCNA and cyclin D1, and enhanced proliferation and cell cycle
progression in pLE cells. CCL23 also stimulated phosphorylation of cell signaling
molecules including AKT and MAPKs in pLE cells. Furthermore, ER stress-related
molecules were reduced by CCL23. These results suggest that CCL23-CCR1 signaling
is important for endometrial development and establishment of pregnancy in pigs.
PMID- 28694170
TI - Safety assessment and toxicological profiling of a novel combinational
sunprotective dermal formulation containing melatonin and pumpkin seed oil.
AB - Ultraviolet (UV) radiation exposure has been known to cause irreparable damages
to human skin. The daunting risk of UV radiation exposure faced by military
personnel led to the development of a sunscreen formulation which has superior
sun protection factor combined with the ability to counteract reactive oxygen
species. The present work deals with the preclinical safety evaluation of the
sunscreen formulation comprising of four US FDA approved UV filters; namely
avobenzone, octinoxate, oxybenzone, titanium dioxide along with melatonin and
pumpkin seed oil, via OECD protocols of assessing acute oral and dermal toxicity;
skin sensitizing; skin irritating; ocular irritating and genotoxic potential.
Both oral and dermal LD50 values were found to be ?2000 mg/kg body weight in
adult Wistar albino rats using acute dermal and oral toxicity tests. The
sunscreen formulation was found to be non-sensitizing to the skin of guinea pigs
and non-irritating to both skin and eyes of rabbits. The sunscreen formulation
was also found to be non-mutagenic which was affirmed by a battery of
genotoxicity and muagenicity assays. The results obtained from this preclinical
study indicated that the sunscreen formulation is non toxic and safe in animal
models. This study along with additional preclinical evaluations may serve as a
basis for considering the formulation as a potential candidate for further trials
to establish its efficacy, tolerability and applicability.
PMID- 28694171
TI - Repeated dose 28-day oral toxicity study of DEAE-Dextran in mice: An advancement
in safety chemotherapeutics.
AB - Cancer has emerged as a global threat with challenges for safe chemotherapeutics.
Most of the currently available anti-cancer drugs exhibit significant toxicity.
Amongst novel agents, interferons have exhibited anti-proliferative and
cytoprotective roles. However, due to stability drawbacks of interferons, we have
identified an interferon inducer DEAE-Dextran, which resolves the stability
issues. Based on the previous history of toxicity pertaining to the current
chemotherapeutic agents, it is equally essential to determine the safety of DEAE
Dextran. In the present study, repeated dose 28 day oral toxicity of DEAE-Dextran
has been evaluated in accordance to OECD-407. We found absence of any CNS
behavioral changes related to self-mutilation, walking backwards, aggressiveness
on handling or tonic-clonic seizures during the 28 day study. Neither the motor
activity nor grip strength was altered during the treatment duration with DEAE
Dextran implying absence of any effect on the skeletal muscles. Interestingly, we
also found that treatment with DEAE-Dextran did not present any significant
cardiac, hepatic, renal, gastrointestinal, lymphatic or reproductive system
toxicity or alteration in the body's normal physiology based upon the various
organ function tests. Henceforth, it may be concluded that DEAE-Dextran is a safe
anti-cancer agent devoid of any sub-acute toxicity.
PMID- 28694172
TI - Macrophage migration inhibitory factor mediates viability and apoptosis of PVM/Ms
through PI3K/Akt pathway.
AB - Macrophage migration inhibitory factor (MIF) plays an important role in hearing
function; however, the underlying mechanism remains indistinct. PVM/Ms from the
stria vascularis of lateral wall of cochlea in young and aged mice were isolated,
and the mRNA and protein expression levels were detected. MIF was knocked down or
overexpresssed in vitro, and transfection was performed in vivo. Cell viability
and apoptosis were determined by MTT assay and flow cytometry analysis,
respectively. The hearing ability was tested by the auditory brain stem response.
The results showed that MIF expression was significantly downregulated in aged
mice. In aged mice, the viability of PVM/Ms significantly decreased, but the
apoptotic number markedly increased. MIF knockdown in PVM/Ms in vitro
significantly inhibited cell viability and induced cell apoptosis, but MIF
overexpression showed contrasting results. Further studies showed that MIF
knockdown in young mice resulted in serious hearing loss, but MIF overexpression
in aged mice restored the hearing. Si-MIF inhibited the viability and induced
apoptosis of PVM/Ms from young mice, whereas Ad-MIF induced the viability and
inhibited apoptosis of PVM/Ms from aged mice. Moreover, MIF effectively altered
the expression levels of CDK1, BRAF, p-ERK1/2, p-PI3K, and p-Akt. Furthermore,
ERK inhibitor PD98059 or PI3K inhibitor LY294002 significantly reversed the
effects of Si-MIF on PVM/Ms from young mice, whereas ERK activator EGF or PI3K
activator IGF significantly reversed the effects of Ad-MIF on PVM/Ms from aged
mice. Taken together, MIF mediates the viability and apoptosis of PVM/Ms, at
least partially, through MAPK and/or PI3K/Akt pathway.
PMID- 28694173
TI - Development of sensitivity to orthographic errors in children: An event-related
potential study.
AB - To study the development of orthographic sensitivity during elementary school, we
recorded event-related brain potentials (ERPs) from 2nd and 4th grade children
who were exposed to line drawing of object or animals upon which the correctly or
incorrectly spelled name was superimposed. Stimulus-locked ERPs showed a
modulation of a frontocentral negativity between 200 and 500ms which was larger
for the 4th grade children but did not show an effect of correctness of spelling.
This effect was followed by a pronounced positive shift which was only seen in
the 4th grade children and which showed a modulation of spelling correctness.
This effect can be seen as an electrophysiological correlate of orthographic
sensitivity and replicates earlier findings in adults. Moreover, response-locked
ERPs triggered to the children's button presses indicating orthographic (in)
correctness showed a succession of waves including the frontocentral error
related negativity and a subsequent negativity with a more posterior
distribution. This latter negativity was generally larger for the 4th grade
children. Only for the 4th grade children, this negativity was smaller for the
false alarm trials suggesting a conscious registration of the error in these
children.
PMID- 28694174
TI - Multidimensional receptive field processing by cat primary auditory cortical
neurons.
AB - The receptive fields of many auditory cortical neurons are multidimensional and
are best represented by more than one stimulus feature. The number of these
dimensions, their characteristics, and how they differ with stimulus context have
been relatively unexplored. Standard methods that are often used to characterize
multidimensional stimulus selectivity, such as spike-triggered covariance (STC)
or maximally informative dimensions (MIDs), are either limited to Gaussian
stimuli or are only able to recover a small number of stimulus features due to
data limitations. An information theoretic extension of STC, the maximum noise
entropy (MNE) model, can be used with non-Gaussian stimulus distributions to find
an arbitrary number of stimulus dimensions. When we applied the MNE model to
auditory cortical neurons, we often found more than two stimulus features that
influenced neuronal firing. Excitatory and suppressive features coded different
acoustic contexts: excitatory features encoded higher temporal and spectral
modulations, while suppressive features had lower modulation frequency
preferences. We found that the excitatory and suppressive features themselves
were sensitive to stimulus context when we employed two stimuli that differed
only in their short-term correlation structure: while the linear features were
similar, the secondary features were strongly affected by stimulus statistics.
These results show that multidimensional receptive field processing is influenced
by feature type and stimulus context.
PMID- 28694175
TI - Daily consumption of methylene blue reduces attentional deficits and dopamine
reduction in a 6-OHDA model of Parkinson's disease.
AB - Recently, alternative drug therapies for Parkinson's disease (PD) have been
investigated as there are many shortcomings of traditional dopamine-based
therapies including difficulties in treating cognitive and attentional
dysfunction. A promising therapeutic avenue is to target mitochondrial
dysfunction and oxidative stress in PD. One option might be the use of methylene
blue (MB), an antioxidant and metabolic enhancer. MB has been shown to improve
cognitive function in both intact rodents and rodent disease models. Therefore,
we investigated whether MB might treat attentional deficits in a rat model of PD
induced by 6-hydroxydopamine (6-OHDA). MB also has neuroprotective capabilities
against neurotoxic insult, so we also assessed the ability of MB to provide
neuroprotection in our PD model. The results show that MB could preserve some
dopamine neurons in the substantia nigra par compacta when 6-OHDA was infused
into the medial forebrain bundle. This neuroprotection did not yield a
significant behavioral improvement when motor functions were measured. However,
MB significantly improved attentional performance in the five-choice task
designed to measure selective and sustained attention. In conclusion, MB might be
useful in improving some attentional function and preserving dopaminergic cells
in this model. Future work should continue to study and optimize the abilities of
MB for the treatment of PD.
PMID- 28694176
TI - Anxiogenic effects of a Lactobacillus, inulin and the synbiotic on healthy
juvenile rats.
AB - Gut microbiota interventions, including probiotic and prebiotic use can alter
behavior in adult animals and healthy volunteers. However, little is known about
their effects in younger individuals. To investigate this, male Sprague-Dawley
rats (post-natal day 21, PND21) received Lactobacillus casei 54-2-33 (104cfu/ml),
inulin as prebiotic (16mg/ml), or both together (synbiotic) via drinking water
for 14days. Control rats received water alone. Open field (OF) and elevated plus
maze (EPM) behaviors were evaluated at PND34 and 35, respectively. 30min after
EPM, brains and trunk blood were collected to evaluate hippocampal 5-HT1A (mRNA
and protein) and plasma corticosterone (CORT). Lactobacillus, inulin and
synbiotic-treated rats had fewer entries to the OF's center and spent more time
in its periphery than controls. Synbiotic-fed rats explored the EPM's open arms
longer than probiotic and inulin-fed rats. Synbiotic, but not Lactobacillus nor
inulin-fed rats had lower levels of EPM-evoked CORT than controls. Basal CORT
levels, evaluated in a naive cohort, were higher in Lactobacillus- and inulin-fed
rats than controls. In naive synbiotic-fed rats, 5-HT1A mRNA levels were higher
in dentate gyrus and cornus ammonis 1 layer (CA1), than in all other naive
groups, while hippocampal 5-HT1A protein levels were lower in bacteria-fed rats
than controls. 5-HT1A mRNA changes suggest complex effects of gut microbes on
hippocampal gene expression machinery, probably involving endogenous/exogenous
bacteria and prebiotics interactions. Importantly, age might also influence their
behavioral outcomes. Together, these data suggest that interventions in young rat
microbiota evoke early behavioral changes upon stress, apparently in a
hypothalamus-pituitary-adrenal axis independent fashion.
PMID- 28694177
TI - Spheroids as vascularization units: From angiogenesis research to tissue
engineering applications.
AB - Multi-cellular spheroids mimic the complex three-dimensional environment of
natural tissues. Accordingly, they are also used as vascularization units in
angiogenesis research and regenerative medicine. Spheroid sprouting assays are
versatile in vitro models for the analysis of molecular and cellular determinants
of blood vessel development, including different endothelial cell phenotypes, pro
and anti-angiogenic factors as well as cell-matrix and cell-cell interactions.
In tissue engineering, spheroids serve in vivo as paracrine stimulators of
angiogenesis and building blocks for the generation of prevascularized
microtissues and branched vascular trees in macrotissues. Rapid progress in the
automatized high-throughput production of spheroids currently provides the
conditions for a widespread use of these applications in future drug discovery
and bioengineering of functional organ substitutes.
PMID- 28694178
TI - Medicinal plants used in the treatment of tuberculosis - Ethnobotanical and
ethnopharmacological approaches.
AB - Tuberculosis is a highly infectious disease declared a global health emergency by
the World Health Organization, with approximately one third of the world's
population being latently infected with Mycobacterium tuberculosis. Tuberculosis
treatment consists in an intensive phase and a continuation phase. Unfortunately,
the appearance of multi drug-resistant tuberculosis, mainly due to low adherence
to prescribed therapies or inefficient healthcare structures, requires at least
20months of treatment with second-line, more toxic and less efficient drugs,
i.e., capreomycin, kanamycin, amikacin and fluoroquinolones. Therefore, there
exists an urgent need for discovery and development of new drugs to reduce the
global burden of this disease, including the multi-drug-resistant tuberculosis.
To this end, many plant species, as well as marine organisms and fungi have been
and continue to be used in various traditional healing systems around the world
to treat tuberculosis, thus representing a nearly unlimited source of active
ingredients. Besides their antimycobacterial activity, natural products can be
useful in adjuvant therapy to improve the efficacy of conventional
antimycobacterial therapies, to decrease their adverse effects and to reverse
mycobacterial multi-drug resistance due to the genetic plasticity and
environmental adaptability of Mycobacterium. However, even if some natural
products have still been investigated in preclinical and clinical studies, the
validation of their efficacy and safety as antituberculosis agents is far from
being reached, and, therefore, according to an evidence-based approach, more high
level randomized clinical trials are urgently needed.
PMID- 28694179
TI - Microalgal-bacterial aggregates: Applications and perspectives for wastewater
treatment.
AB - Research on wastewater treatment by means of microalgal-bacterial processes has
become a hot topic worldwide during the last two decades. Owing to the lower
energy demand for oxygenation, the enhanced nutrient removal and the potential
for resource recovery, microalgal-based technologies are nowadays considered as a
good alternative to conventional activated sludge treatments in many instances.
Nevertheless, biomass harvesting still constitutes one of the major challenges of
microalgal-bacterial systems for wastewater treatment, which is hindered by the
poor settleability of microalgal biomass. In this review, the use of microalgal
bacterial aggregates (MABAs) to overcome harvesting issues and to enhance
resource recovery is presented. The fundamentals of MABAs-based technologies, the
operational strategies and factors affecting the formation of MABAs, the
microbiology and the methanogenic potential of the aggregates are addressed and
critically discussed. The most recent findings and the challenges facing this
technology towards its consolidation are also presented.
PMID- 28694180
TI - Myocardial bridge as a cause of pseudo-Wellens' syndrome.
PMID- 28694181
TI - Allopregnanolone involvement in feeding regulation, overeating and obesity.
AB - Obesity is strongly associated with ill health, primarily caused by consumption
of excessive calories, and promoted (inter alia) by gamma-amino-butyric-acid
(GABA) stimulating food intake by activating GABAA receptors (primarily with
alpha3 and alpha2 subunits) in the hypothalamic arcuate nucleus and
paraventricular nucleus. Allopregnanolone is a potent positive GABAA receptor
modulating steroid (GAMS). As reviewed here, elevated allopregnanolone levels are
associated with increases in food intake, preferences for energy-rich food, and
obesity in humans and other mammals. In women with polycystic ovarian disease,
high serum allopregnanolone concentrations are linked to uncontrolled eating, and
perturbed sensitivity to allopregnanolone. Increases in weight during pregnancy
also correlate with increases in allopregnanolone levels. Moreover, Prader-Willis
syndrome is associated with massive overeating, absence of a GABAA receptor (with
compensatory >12-, >5- and >1.5-fold increases in alpha4, gamma2, and alpha1,
alpha3 subunits), and increases in the alpha4, betax, delta receptor subtype,
which is highly sensitive to allopregnanolone. GABA and positive GABA-A receptor
modulating steroids like allopregnanolone stimulates food intake and weight gain.
PMID- 28694182
TI - Allogeneic Hematopoietic Stem Cell Transplantation with Myeloablative
Conditioning Is Associated with Favorable Outcomes in Mixed Phenotype Acute
Leukemia.
AB - Mixed phenotype acute leukemia (MPAL) represents a poorly characterized group of
acute leukemias that lack an accepted therapeutic approach and are typically
associated with poor outcomes. We present our experience of genomic profiling,
pretransplantation therapy, and transplantation outcomes for 36 well
characterized pediatric and adult patients with MPAL, defined according to the
2016 World Health Organization leukemia update. A predominance of acute lymphoid
leukemia (ALL)-associated mutations and cytogenetic abnormalities was noted.
Remission rates after induction appeared comparable among adults (20 of 23) and
children (11 of 13) and among those who received ALL (10 of 11) or acute myeloid
leukemia-type (21 of 25) induction. Adults underwent transplantation in first
remission while children underwent transplantation in the setting of relapse or
MLL rearrangement. The median follow-up among the 25 patients who underwent
transplantation was 39.6 months and median overall survival was not reached.
Relapse after transplantation was associated with MLL rearrangement (P = .022),
reduced-intensity conditioning (P < .001), and higher WBC at diagnosis (P =
.034). These data highlight differing therapeutic approaches between adult and
pediatric MPAL and demonstrate favorable survival of adult MPAL patients
consolidated with allogeneic hematopoietic cell transplantation.
PMID- 28694183
TI - STAT3 Expression in Host Myeloid Cells Controls Graft-versus-Host Disease
Severity.
AB - Professional antigen-presenting cells (APCs) are important modulators of acute
graft-versus-host disease (GVHD). Although dendritic cells (DCs) are the most
potent APC subset, other myeloid cells, especially macrophages (MFs) and
neutrophils, recently have been shown to play a role in the severity of GVHD. The
critical molecular mechanisms that determine the functions of myeloid cells in
GVHD are unclear, however. Signal transducer and activator of transcription 3
(STAT3) is a master transcription factor that plays a crucial role in regulating
immunity, but its role in MF biology and in acute GVHD remains unknown. To
determine the impact of myeloid cell-specific expression of STAT3 on the severity
of acute GVHD, we used myeloid cell-specific STAT3-deficient LysM-Cre/STAT3fl/-
animals as recipients and donors in well-characterized experimental models of
acute GVHD. We found that reduced expression of STAT3 in myeloid cells from the
hosts, but not the donors, increased inflammation, increased donor T cell
activation, and exacerbated GVHD. Our data demonstrate that STAT3 in host myeloid
cells, such as MFs, dampens acute GVHD.
PMID- 28694184
TI - Engineering yeasts as platform organisms for cannabinoid biosynthesis.
AB - Delta9-tetrahydrocannabinolic acid (THCA) is a plant derived secondary natural
product from the plant Cannabis satival. The discovery of the human
endocannabinoid system in the late 1980s resulted in a growing number of known
physiological functions of both synthetic and plant derived cannabinoids. Thus,
manifold therapeutic indications of cannabinoids currently comprise a significant
area of research. Here we reconstituted the final biosynthetic cannabinoid
pathway in yeasts. The use of the soluble prenyltransferase NphB from
Streptomyces sp. strain CL190 enables the replacement of the native transmembrane
prenyltransferase cannabigerolic acid synthase from C. sativa. In addition to the
desired product cannabigerolic acid, NphB catalyzes an O-prenylation leading to 2
O-geranyl olivetolic acid. We show for the first time that the bacterial
prenyltransferase and the final enzyme of the cannabinoid pathway
tetrahydrocannabinolic acid synthase can both be actively expressed in the yeasts
Saccharomyces cerevisiae and Komagataella phaffii simultaneously. While enzyme
activities in S. cerevisiae were insufficient to produce THCA from olivetolic
acid and geranyl diphosphate, genomic multi-copy integrations of the enzyme's
coding sequences in K. phaffii resulted in successful synthesis of THCA from
olivetolic acid and geranyl diphosphate. This study is an important step toward
total biosynthesis of valuable cannabinoids and derivatives and demonstrates the
potential for developing a sustainable and secure yeast bio-manufacturing
platform.
PMID- 28694185
TI - Enhanced production of nisin by co-culture of Lactococcus lactis sub sp. lactis
and Yarrowia lipolytica in molasses based medium.
AB - Nisin is a safe, approved and commercial bacteriocin that is produced by
Lactococcus lactis subsp. lactis. Since lactate accumulation in fermentation
medium reduces L. lactis growth and nisin production, Yarrowia lipolytica, a
lactate consuming yeast and L. lactis subsp. lactis, were simultaneously cultured
in a molasses based medium. Y. lipolytica is not able to consume sucrose as
carbon source, but rather consumes lactate and hence decrease lactic acid titer
by 10% in the medium. Lactic acid consumption, 15% increased pH value and
stimulated L. lactis growth. In the mixed culture, nisin production and L. lactis
growth were 50% and 49% higher than that of pure culture, respectively. Also the
results showed that specific growth rate of L. lactis increased 4 times more than
that of the pure culture.
PMID- 28694186
TI - The role of exercise in atrial fibrillation prevention and promotion: Finding
optimal ranges for health.
AB - The cardiovascular benefits of regular exercise have been well described,
including a significant reduction in cardiovascular morbidity and mortality for
those meeting recommended guidelines. Yet the impact of physical activity on the
incidence of atrial fibrillation (AF) has been less clear. This review seeks to
define the optimal dose and duration for the prevention and treatment of AF. In
doing so, we review the evidence that supports a decline in AF risk for those who
achieve a weekly physical activity dose slightly above the current recommended
guidelines. Furthermore, we identify the reduced AF incidence in those
individuals who attain a cardiorespiratory fitness of 8 METs (metabolic
equivalents of task) or more during maximal exercise testing. Finally, we review
the evidence that shows an excess of AF among regular participants of endurance
exercise.
PMID- 28694187
TI - A more sensitive, efficient and ISO 17025 validated Magnetic Capture real time
PCR method for the detection of archetypal Toxoplasma gondii strains in meat.
AB - Toxoplasma gondii is a globally prevalent, zoonotic parasite of major importance
to public health. Various indirect and direct methods can be used for the
diagnosis of toxoplasmosis. Whereas serological tests are useful to prove contact
with the parasite has occurred, the actual presence of the parasite in the
tissues of a seropositive animal is not demonstrated. For this, a bioassay is
still the reference method. As an alternative, various PCR methods have been
developed, but due to the limited amount of sample that can be tested, combined
with a low tissue cyst density, those have proved to be insufficiently sensitive.
A major improvement of the sensitivity was achieved with magnetic capture-based
DNA extraction. By combining the hybridization of specific, biotinylated probes
with the capture of those probes with streptavidin-coated paramagnetic beads, T.
gondii DNA can selectively be "fished out" from a large volume of meat lysate.
Still, several studies showed an insufficient sensitivity compared with the mouse
bioassay. Here we present a method that is more sensitive (99% limit of
detection: 65.4 tachyzoites per 100g of meat), economical and reliable (ISO 17025
validated) by adding a non-competitive PCR inhibition control (co-capture of
cellular r18S) and making the release of the target DNA from the streptavidin
coated paramagnetic beads UV-dependent. The presented results demonstrate the
potential of the modified Magnetic Capture real time PCR as a full alternative to
the mouse bioassay for the screening of various types of tissues and meat, with
the additional advantage of being quantitative.
PMID- 28694188
TI - Testing the enemy release hypothesis: abundance and distribution patterns of
helminth communities in grey mullets (Teleostei: Mugilidae) reveal the success of
invasive species.
AB - The abundance and aggregation patterns of helminth communities of two grey mullet
hosts, Liza haematocheilus and Mugil cephalus, were studied across 14 localities
in Atlantic and Pacific marine areas. The analysis matched parasite communities
of (i) L. haematocheilus across its native and introduced populations (Sea of
Japan and Sea of Azov, respectively) and (ii) the introduced population of L.
haematocheilus with native populations of M. cephalus (Mediterranean, Azov-Black
and Japan Seas). The total mean abundance (TMA), as a feature of the infection
level in helminth communities, and slope b of the Taylor's power law, as a
measure of parasite aggregation at the infra and component-community levels, were
estimated and compared between host species and localities using ANOVA. The TMA
of the whole helminth community in the introduced population of L. haematocheilus
was over 15 times lower than that of the native population, but the difference
was less pronounced for carried (monogeneans) than for acquired (adult and larval
digeneans) parasite communities. Similar to the abundance pattern, the species
distribution in communities from the invasive population of L. haematocheilus was
less aggregated than from its native population for endoparasitic helminths,
including adult and larval digeneans, while monogeneans showed a similar pattern
of distribution in the compared populations of L. haematocheilus. The aggregation
level of the whole helminth community, endoparasitic helminths, adult and larval
digeneans was lower in the invasive host species in comparison with native ones
as shown by differences in the slope b. An important theoretical implication from
this study is that the pattern of parasite aggregation may explain the success of
invasive species in ecosystems. Because the effects of parasites on host
mortality are likely dose-dependent, the proportion of susceptible host
individuals in invasive species is expected to be lower, as the helminth
distribution in the invasive host was featured by a higher number of uninfected
hosts and a shorter distribution tail when compared with native species.
PMID- 28694189
TI - Structural studies on the decameric S. typhimurium arginine decarboxylase (ADC):
Pyridoxal 5'-phosphate binding induces conformational changes.
AB - Enteric pathogens such as Salmonella typhimurium colonize the human gut in spite
of the lethal acidic pH environment (pH < 2.5) due to the activation of inducible
acid tolerance response (ATR) systems. The pyridoxal 5'-phosphate (PLP)-dependent
enzyme, biodegradative arginine decarboxylase (ADC, encoded by AdiA), is a
component of an ATR system. The enzyme consumes a cytoplasmic proton in the
process of arginine degradation to agmatine. Arginine-agmatine antiporter (AdiC)
exchanges the product agmatine for arginine. In this manuscript, we describe the
structure of Salmonella typhimurium ADC (StADC). The decameric structure
assembled from five dimers related by a non crystallographic 5-fold symmetry
represents the first apo-form of the enzyme. The structure suggests that PLP
binding is not a prerequisite for oligomerization. Comparison with E. coli ADC
reveals that PLP-binding is accompanied by the movement and ordering of two loops
(residues 150-159 and 191-197) and a few active site residues such as His256 and
Lys257. A number of residues important for substrate binding are disordered in
the apo-StADC structure indicating that PLP binding is important for substrate
binding. Unlike the interactions between 5-fold related protomers, interactions
that stabilize the dimeric structure are not pH dependent.
PMID- 28694190
TI - Non-canonical pathway induced by Wnt3a regulates beta-catenin via Pyk2 in
differentiating human neural progenitor cells.
AB - Wnt/beta-catenin and Wnt/Ca2+ pathways are involved in cellular processes during
embryonic development and the interaction between them in the same cell decides
the outcome of cellular functions. In this study, we showed that Wnt3a triggers
the Wnt/Ca2+ signaling pathway, indicated by an increase of cytosolic free
calcium ([Ca2+]i) and activation of calmodulin dependent kinase II (CaMKII)
during the differentiation of human neuronal progenitor cells (hNPCs). Wnt3a via
the increase of [Ca2+]i activates proline-rich tyrosine kinase 2 (Pyk2), which
subsequently regulates phosphorylation of glycogen synthase kinase 3beta
(GSK3beta) and beta-catenin stabilization. Our findings suggest that Pyk2 plays
an important role in the coordination of stabilization of beta-catenin in the
crosstalk between Wnt/beta-catenin and Wnt/Ca2+ signaling pathways upon Wnt3a
stimulation in differentiating hNPCs.
PMID- 28694191
TI - On the role of subunit M in cytochrome cbb3 oxidase.
AB - Cytochrome cbb3 (or C-type) oxidases are a highly divergent group and the least
studied members of the heme-copper oxidases (HCOs) superfamily. HCOs couple the
reduction of oxygen at the end of the respiratory chain to the active proton
translocation across the membrane, contributing to establishment of an
electrochemical gradient essential for ATP synthesis. Cbb3 oxidases exhibit
unique structural and functional features and have an essential role in the
metabolism of many clinically relevant human pathogens. Such characteristics make
them a promising therapeutic target. Three subunits, N, O and P, comprise the
core cbb3 complex, with N, the catalytic subunit, being highly conserved among
all members of the HCO superfamily, including the A-type (aa3, mitochondrial
like) oxidases. An additional fourth subunit containing a single transmembrane
(TM) helix was present in the first crystal structure of cbb3. This TM segment
was recently proposed to be part of a novel protein CcoM, which was shown to have
a putative role in the complex stability and assembly. In this work, we performed
large-scale all-atom molecular dynamics simulations of the CcoNOPM complex to
further characterize the interactions between subunit M and the core subunits and
to determine whether the presence of the fourth subunit influences the
water/proton channels previously described for the core complex. The previously
proposed putative CcoNOPH complex is also assessed, and the potential functional
redundancy of CcoM and CcoQ is discussed.
PMID- 28694192
TI - Laminar shear stress suppresses vascular smooth muscle cell proliferation through
nitric oxide-AMPK pathway.
AB - In healthy condition, vascular smooth muscle cells (VSMCs) are not directly
exposed to shear stresses, because they are shielded by endothelial cell (EC)
layer that lines blood vessels. After injury to EC layer caused by rupture of
atherosclerotic lesions or invasive techniques such as angioplasty, VSMCs are
directly exposed to blood flow which modulate molecular signaling and function.
In endothelium, exposure to fluid shear stress has been reported to induce AMP
activated protein kinase (AMPK) phosphorylation and nitric oxide (NO) production.
However, the influence of laminar shear stress on exposed VSMC is not defined. In
this study, we investigated whether laminar shear stress regulates AMPK
phosphorylation in VSMC and tried to identify underlying signaling pathway. NO
production was increased by shear stress. The expression of NOS isoforms was
increased 1 h after exposure to shear stress, and AMPK phosphorylation started to
increase after 2 h. AMPK and LKB1, the upstream kinases of AMPK, phosphorylation
were decreased by the non-selective NOS inhibitor l-NAME and the selective iNOS
inhibitor aminoguanidine despite exposure to shear stress. On the other hand,
compound C, a specific AMPK inhibitor, did not affect the expression of NOS
isoforms. In addition, PDGF-induced VSMC proliferation was decreased by shear
stress and restored by l-NAME. These findings suggest that shear stress
upregulated AMPK phosphorylation in VSMC via NOS expression may be a beneficial
route to prevent pathogenesis in the vascular system.
PMID- 28694193
TI - Mutant analysis of Cdt1's function in suppressing nascent strand elongation
during DNA replication in Xenopus egg extracts.
AB - The initiation of DNA replication is strictly regulated by multiple mechanisms to
ensure precise duplication of chromosomes. In higher eukaryotes, activity of the
Cdt1 protein is temporally regulated during the cell cycle, and deregulation of
Cdt1 induces DNA re-replication. In previous studies, we showed that excess Cdt1
inhibits DNA replication by suppressing progression of replication forks in
Xenopus egg extracts. Here, we investigated the functional regions of Cdt1 that
are required for the inhibition of DNA replication. We constructed a series of N
terminally or C-terminally deleted mutants of Cdt1 and examined their inhibitory
effects on DNA replication in Xenopus egg extracts. Our results showed that the
region spanning amino acids (a. a.) 255-620 is required for efficient inhibition
of DNA replication, and that, within this region, a. a. 255-289 have a critical
role in inhibition. Moreover, one of the Cdt1 mutants, Cdt1 R285A, was
compromised with respect to the licensing activity but still inhibited DNA
replication. This result suggests that Cdt1 has an unforeseen function in the
negative regulation of DNA replication, and that this function is located within
a molecular region that is distinct from those required for the licensing
activity.
PMID- 28694194
TI - LYRM7 - associated complex III deficiency: A clinical, molecular genetic, MR
tomographic, and biochemical study.
AB - LYRM7 is involved in the last steps of mitochondrial complex III assembly where
it acts as a chaperone for the Rieske iron-sulfur (Fe-S) protein in the
mitochondrial matrix. Using exome sequencing, we identified homozygosity for a
splice site destroying 4 base pair deletion in LYRM7 in a child with recurrent
lactic acidotic crises and distinct early-onset leukencephalopathy. Sanger
sequencing showed variant segregation in similarly affected family members.
Functional analyses revealed a reduced amount of the Rieske Fe-S protein, which
was restored after re-expression of LYRM7. Our data provide further evidence for
the importance of LYRM7 for mitochondrial function and emphasize the importance
of whole exome sequencing in the diagnosis of rare mitochondrial diseases.
PMID- 28694195
TI - Hemoglobins emerging roles in mental disorders. Metabolical, genetical and
immunological aspects.
AB - Hemoglobin (Hb) expression in the central nervous system is recently shown.
Cooccurences of mental disorders (mainly bipolar disorder (BD) and tic disorders)
with beta- or alpha-thalassemia trait or erythrocytosis were witnessed, which may
be due to peripheral or central hypoxia/hyperoxia or haplotypal gene
interactions. beta-Globin genes reside at 11p15.5 close to tyrosine hydroxylase,
dopamine receptor DRD4 and Brain Derived Neurotrophic Factor, which involve in
psychiatric diseases. alpha-Globin genes reside at 16p13.3 which associates with
BD, tic disorders, ATR-16 Syndrome and Rubinstein Taybi Syndrome (RTS). CREB
Binding Protein (CEBBP)-gene is mutated in RTS, which commonly associates with
mood disorders. 16p13.3 region also contains GRIN2A gene encoding N-methyl-d
aspartate receptor-2A and SSTR5 (Somatostatin Receptor-5), again involving in
mental disorders. We demonstrated a protective role of minor HbA2 against post
partum episodes in BD and association of higher minor HbF (fetal hemoglobin)
levels with family history of psychosis in a BD-patient cohort. HbA2 increases in
cardiac ischemia and in mountain dwellers indicating its likely protection
against ischemia/hypoxia. HMGIY, a repressive transcription factor of delta
globin chain of HbA2 is increased in lymphocytes of schizophrenics. In autism,
deletional mutations were found in BCL11A gene, which cause persistence of HbF at
high levels in adulthood. Also, certain polymorphisms in BCL11A strongly
associate with schizophrenia. Further, many drugs from anabolic steroids to
antimalarial agents elevate HbF and may cause mania. We ascribe a protective role
to HbA2 and a maladaptive detrimental role to HbF in psychopathology. We believe
that future studies on hemoglobins may pave to discover novel pathogenesis
mechanisms in mental disorders.
PMID- 28694196
TI - Effect of sulfonated steroids on steroidogenic cytochrome P450-dependent steroid
hydroxylases.
AB - In the last decades, sulfonated steroids evolved from inactive metabolites
intended for excretion to highly relevant compounds involved in many
physiological processes. Investigations of the impact of sulfonated steroids on
the steroid hormone biosynthesis revealed that, on the one hand, these can serve
as substrate for steroidogenic cytochromes P450 and, on the other hand, these are
able to influence the catalytic properties of these enzymes. In this review the
relevance of sulfonated steroids for the steroid hormone biosynthesis will be
discussed.
PMID- 28694197
TI - Feasibility, Safety, and Utility of Advanced Critical Care Transesophageal
Echocardiography Performed by Pulmonary/Critical Care Fellows in a Medical ICU.
AB - BACKGROUND: Competence in advanced critical care transesophageal echocardiography
allows the intensivist to diagnose and manage cardiopulmonary failure when
transthoracic echocardiography is not sufficient to answer the clinical question.
This report describes the feasibility, safety, and utility of transesophageal
echocardiography performed by pulmonary and critical care fellows in a medical
ICU in critically ill patients who were mechanically ventilated. METHODS: This
longitudinal descriptive study of advanced transesophageal echocardiography was
performed in patients who were mechanically ventilated. The complications and
clinical utility of the examinations were abstracted from review of the image
set, the written report, and the patient chart. Influence on diagnosis was
classified as confirming the initial clinical diagnosis or identification of a
new or unanticipated finding. Therapeutic impact was categorized as no change in
therapy resulting from the study findings or as change in therapy resulting from
the study findings. RESULTS: The examination was feasible in all patients in whom
it was attempted, and there were no complications of the procedure. New or
actionable findings were identified in 43 (28%) studies, and 109 (72%) studies
confirmed the initial clinical diagnosis. The findings resulted in a change in
clinical management in 58 (38%) patients. CONCLUSIONS: Critical care
transesophageal echocardiography is feasible, safe, and has clinical utility. It
can be safely and effectively performed by fellows within the context of their
critical care training with faculty supervision. Pulmonary critical care
fellowship training programs should consider introducing critical care
transesophageal echocardiography as a useful clinical tool.
PMID- 28694199
TI - Initiation of Noninvasive Ventilation for Sleep Related Hypoventilation
Disorders: Advanced Modes and Devices.
AB - Although noninvasive ventilation (NIV) has been used since the 1950s in the polio
epidemic, the development of modern bilevel positive airway pressure (BPAP)
devices did not become a reality until the 1990s. Over the past 25 years, BPAP
technology options have increased exponentially. The number of patients receiving
this treatment both in the acute setting and at home is growing steadily.
However, a knowledge gap exists in the way the settings on these devices are
adjusted to achieve synchrony and match the patient's unique physiology of
respiratory failure. This issue is further complicated by differences in pressure
and flow dynamic settings among different types of NIV devices available for
inpatient and home care.
PMID- 28694198
TI - Surviving With Smog and Smoke: Precision Interventions?
AB - Despite continuous efforts of regional governmental agencies, air pollution
remains a major threat to public health worldwide. In January 2017, a severe
episode of smog similar to the Great Smog of 1952 occurred in London. The longest
episode of Chinese haze also developed in Beijing, during which levels of
particulate matter < 2.5 MUm rose to 500 MUg/m3. European smog and Chinese haze
are associated with large numbers of premature deaths each year, at 400,000 and
1.2 million, respectively, primarily from respiratory diseases, cerebrovascular
diseases, and ischemic heart diseases. In addition to air pollution, some are
exposed to other harmful environmental factors, such as secondhand smoke. For
countries with large populations of smokers, such as China, India, the United
States, and Russia, surviving both smog and smoke is a serious problem. With
novel genomic and epigenomic studies revealing air pollution- and smoking-induced
mutational signatures and epigenetic editing in diseases such as lung cancer, it
has become feasible to develop precision strategies for early intervention in the
disease-causing pathways driven by the specific mutations or epigenetic
regulations, or both. New therapies guided by gene-drug interactions and genomic
biomarkers may also be developed. We discuss both perspectives regarding the
urgent need to manage the toxic effects of smog and smoke for the benefit of
global health and the novel concept of precision intervention to protect the
exposed individuals when exposure to smog and secondhand smoke cannot be
voluntarily avoided or easily modified.
PMID- 28694200
TI - Prevention and Treatment of Smoking and Tobacco Use During Pregnancy in Selected
Indigenous Communities in High-Income Countries of the United States, Canada,
Australia, and New Zealand: An Evidence-Based Review.
AB - Tobacco smoking during pregnancy is the most important modifiable risk factor for
adverse pregnancy outcomes and long-term health complications for mother and
baby. Tobacco use during pregnancy has decreased in high-income countries but not
in Indigenous women in Australia, New Zealand, the United States, and Canada.
This evidence-based review focuses on tobacco use among Indigenous pregnant women
in high-income countries that share a history of European colonization.
Indigenous women are more likely to use tobacco because of socioeconomic
disadvantage, social norms, and poor access to culturally appropriate tobacco
cessation support. Complications arising from tobacco smoking during pregnancy,
such as low birth weight, prematurity, perinatal death, and sudden infant death
syndrome, are much higher in Indigenous populations. Effective approaches to
cessation in pregnant nonindigenous women involves behavioral counseling, with or
without nicotine replacement therapy (NRT). Higher nicotine metabolism during
pregnancy and poor adherence may affect therapeutic levels of NRT. Only two
randomized trials were conducted among Indigenous women: neither found a
statistically significant difference in cessation rates between the treatment and
comparison arms. Considerations should be given to (1) whole life course
approaches to reduce tobacco use in Indigenous women, (2) prohibiting tobacco
promotion and reducing access to alcohol for minors to prevent smoking initiation
in Indigenous youth, and (3) training health-care professionals in culturally
appropriate smoking cessation care to improve access to services. It is critical
to ensure acceptability and feasibility of study designs, consult with the
relevant Indigenous communities, and preempt implementation challenges. Research
is needed into the effect of reducing or stopping smoking during pregnancy when
using NRT on subsequent maternal and infant outcomes.
PMID- 28694201
TI - Use of QuantiFERON-TB Gold In-tube assay in screening for neutralizing anti
interferon-gamma autoantibodies in patients with disseminated nontuberculous
mycobacterial infection.
AB - OBJECTIVE: Anti-interferon- gamma (IFN-gamma) autoantibodies (anti-IFN-gamma Abs)
have been increasingly recognized as an important cause of disseminated
nontuberculous mycobacterial (DNTM) infection, and identification of this
immunodeficiency impacts clinical management. However, the protean disease
manifestations and inaccessibility to diagnostic tests in clinical settings
hamper its early diagnosis. Here, we sought to determine whether QuantiFERON-TB
Gold In-tube (QFT-GIT), a commercialized IFN-gamma release assay, could be used
to screen for neutralizing anti-IFN-gamma Abs among previously healthy adults
with DNTM infection. METHODS: Non-HIV patients with DNTM infection were
prospectively enrolled for the QFT-GIT assays. We measured their plasma
concentration of anti-IFN-gamma Abs and their neutralizing capacity through
enzyme-linked immunosorbent assay and flow cytometry. We then analysed the
correlation between QFT-GIT results and the presence of neutralizing anti-IFN
gamma Abs among patients with and without previously recognized
immunosuppression, respectively. RESULTS: Irrespective of the autoantibody
concentration or disease activity, all patients with neutralizing anti-IFN-gamma
Abs (100%, 30/30) had indeterminate QFT-GIT results because of extremely low or
undetectable IFN-gamma levels in the mitogen tubes. None of the four DNTM
patients who were previously healthy and tested negative of anti-IFN-gamma Abs
had an indeterminate QFT-GIT result, and their IFN-gamma levels in the mitogen
tube were significantly higher than those of the patients with anti-IFN-gamma Abs
(8.28 IU/mL vs. 0.05 IU/mL, p 0.001). CONCLUSION: An indeterminate QFT-GIT result
because of undetectable or extremely low IFN-gamma level in the mitogen tube
suggests the presence of neutralizing anti-IFN-gamma Abs in a previously healthy
patient with DNTM infection.
PMID- 28694202
TI - Comparative outcomes of cefazolin versus nafcillin for methicillin-susceptible
Staphylococcus aureus bacteraemia: a prospective multicentre cohort study in
Korea.
AB - OBJECTIVES: No randomized controlled trials have evaluated the comparative
outcomes of cefazolin versus nafcillin for methicillin-susceptible Staphylococcus
aureus (MSSA) bacteraemia. METHODS: A prospective observational cohort study
including all S. aureus bacteraemia was conducted at 10 hospitals. Patients (>=15
years) with MSSA bacteraemia who received cefazolin or nafcillin as definitive
antibiotics were included. The rates of treatment failure (premature
discontinuation of antibiotics because of adverse effects, switching of
antibiotics because of clinical failure, all-cause mortality within 1 month, or
recurrence) were compared between the cefazolin and nafcillin groups. Propensity
score matching analyses were performed to balance the factors influencing the
selection of antibiotics. RESULTS: Among the 242 included cases, the bones and
joints (36.8%) were the most common sites of infection and 60.7% of the patients
had sepsis. The overall treatment failure rate was 43.8% (106/242). All-cause
mortality within 1 month was 6.2% (15/242). After propensity score matching, the
treatment failure rate of cefazolin was lower than that of nafcillin (30.4%
(24/79) vs. 49.4% (39/79), p 0.015) because of a higher rate of discontinuation
caused by adverse events. When the data were limited to patients with sepsis, the
treatment failure rates of both groups were not significantly different.
Approximately 22% (24/110) of MSSA isolates exhibited a cefazolin-inoculum effect
(CIE) that had significant impact on the failure rate and mortality of the
cefazolin group. CONCLUSIONS: Cefazolin might be recommended as an adequate and
better-tolerated treatment for MSSA bacteraemia in the absence of CIE.
PMID- 28694203
TI - Soluble epoxide hydrolase inhibitor AUDA decreases bleomycin-induced pulmonary
toxicity in mice by inhibiting the p38/Smad3 pathways.
AB - Bleomycin (BLM) has potent tumor cell-killing properties that have given it an
important place in cancer chemotherapy, but pulmonary toxicity is its major
adverse effect. Soluble epoxide hydrolase (sEH) inhibitors have been reported to
have protective effects in fibrosis models, but the effects of AUDA, an sEH
inhibitor of BLM-induced pulmonary toxicity and fibrosis, remain to be
researched. In this study, we assessed the effects of AUDA on the BLM-induced
pulmonary fibrosis in a mouse model, and transforming growth factor (TGF)-beta1
induced epithelial proliferation and epithelial-mesenchymal transition (EMT) in
vitro by monitoring changes in pulmonary function, inflammatory response,
fibrotic remodeling, and signaling pathways. AUDA was administered by
intragastric administration (i.g) daily for three weeks, starting at seven days
after intratracheal instillation of BLM. All examinations were performed 24h
after the last i.g. In vivo, AUDA significantly improved BLM-induced decline in
lung function and body weight, and inhibited inflammatory cell accumulation and
the mRNA and protein expression of interleukin (IL)-1beta, TGF-beta1, and matrix
metalloproteinase 9 (MMP-9) in lung tissue. Moreover, AUDA attenuated BLM-induced
deposition of collagen fibers, destruction of alveolar structures, and pulmonary
parenchyma. Additionally, AUDA regulated the expression of alpha-smooth muscle
actin (alpha-SMA) and E-cadherin by inhibiting the Smad3/p38 signaling pathway.
In vitro, AUDA significantly inhibited TGF-beta1-induced epithelial cells and
fibroblast proliferation, reduced sEH expression and alpha-SMA expression, and
increased epoxyeicosatrienoic acid (EET) levels and E-cadherin expression in
epithelial cells. These effects were blocked by AUDA by downregulating the Smad3
and p38 signaling pathways. Taken together, these data indicate that treatment
with sEH inhibitors may improve BLM-induced pulmonary toxicity.
PMID- 28694205
TI - Association of variants in SH2B1 and RABEP1 with worsening of low-density
lipoprotein and glucose parameters in patients treated with psychotropic drugs.
AB - Genetic factors associated with Body Mass Index (BMI) have been widely studied
over the last decade. We examined whether genetic variants previously associated
with BMI in the general population are associated with cardiometabolic parameter
worsening in the psychiatric population receiving psychotropic drugs, a high-risk
group for metabolic disturbances. Classification And Regression Trees (CARTs)
were used as a tool capable of describing hierarchical associations, to pinpoint
genetic variants best predicting worsening of cardiometabolic parameters (i.e
total, HDL and LDL-cholesterol, triglycerides, body mass index, waist
circumference, fasting glucose, and blood pressure) following prescription of
psychotropic drugs inducing weight gain in a discovery sample of 357 Caucasian
patients. Significant findings were tested for replication in a second Caucasian
psychiatric sample (n=140). SH2B1 rs3888190C>A was significantly associated with
LDL levels in the discovery and in the replication sample, with A-allele carriers
having 0.2mmol/l (p=0.005) and 0.36mmol/l (p=0.007) higher LDL levels compared to
others, respectively. G-allele carriers of RABEP1 rs1000940A>G had lower fasting
glucose levels compared to others in both samples (-0.16mmol/l; p<0.001 and
0.77mmol/l; p=0.03 respectively). The present study is the first to observe such
associations in human subjects, which may in part be explained by a high risk
towards dyslipidemia and diabetes in psychiatric patients receiving psychotropic
treatments compared to population-based individuals. These results may therefore
give new insight into the etiology of LDL-cholesterol and glucose regulation in
psychiatric patients under psychotropic drug therapy.
PMID- 28694204
TI - The Mind Body-Wellness in Supportive Housing (Mi-WiSH) study: Design and
rationale of a cluster randomized controlled trial of Tai Chi in senior housing.
AB - Supporting the health of growing numbers of frail older adults living in
subsidized housing requires interventions that can combat frailty, improve
residents' functional abilities, and reduce their health care costs. Tai Chi is
an increasingly popular multimodal mind-body exercise that incorporates physical,
cognitive, social, and meditative components in the same activity and offers a
promising intervention for ameliorating many of the conditions that lead to poor
health and excessive health care utilization. The Mind Body-Wellness in
Supportive Housing (Mi-WiSH) study is an ongoing two-arm cluster randomized,
attention-controlled trial designed to examine the impact of Tai Chi on
functional indicators of health and health care utilization. We are enrolling
participants from 16 urban subsidized housing facilities (n=320 participants),
conducting the Tai Chi intervention or education classes and social calls
(attention control) in consenting subjects within the facilities for one year,
and assessing these subjects at baseline, 6months, and 1year. Physical function
(quantified by the Short Physical Performance Battery), and health care
utilization (emergency visits, hospitalizations, skilled nursing and nursing home
admissions), assessed at 12months are co-primary outcomes. Our discussion
highlights our strategy to balance pragmatic and explanatory features into the
study design, describes efforts to enhance site recruitment and participant
adherence, and summarizes our broader goal of post study dissemination if
effectiveness and cost-effectiveness are demonstrated, by preparing training and
protocol manuals for use in housing facilities across the U.S.
PMID- 28694206
TI - Identification of two novel SH3PXD2B gene mutations in Frank-Ter Haar syndrome by
exome sequencing: Case report and review of the literature.
AB - BACKGROUND: Frank-Ter Haar syndrome (FTHS) is an autosomal-recessive disorder
characterized by skeletal, cardio-vascular, and eye abnormalities, such as
increased intraocular pressure, prominent eyes, and hypertelorism. The most
common underlying genetic defect in Frank-Ter Haar syndrome appears to be due to
mutations in the SH3PXD2B gene on chromosome 5q35.1. Until now, only six
mutations in SH3PXD2B gene have been identified. A genetic heterogeneity of FTHS
was suggested in previous studies. DESIGN: FTHS was suspected clinically in a
girl of 2years old, born from non-consanguineous Moroccan healthy parents. The
patient had been referred to a medical genetics outpatient clinic for dysmorphic
facial features. Whole Exome Sequencing (WES) was performed in the patient and
her parents, in addition to Sanger sequencing that was carried out to confirm the
results. RESULTS: We report the first description of a Moroccan FTHS patient with
two novel compound heterozygous mutations c.806G>A; p.Trp269* (maternal allele)
and c.892delC; p.Asp299Thrfs*44 (paternal allele) in the SH3PXD2B gene. Sanger
sequencing confirmed this mutation in the affected girl and demonstrated that her
parents carry this mutation in heterozygous state. CONCLUSION: Our results
confirm the clinical diagnosis of FTHS in this reported family and contribute to
expand the mutational spectrum of this rare disease. Our study shows also, that
exome sequencing is a powerful and a cost-effective tool for the diagnosis of a
supposed genetically heterogeneous disorder such FTHS.
PMID- 28694207
TI - Cinnamon extracts exert intrapancreatic cytoprotection against streptozotocin in
vivo.
AB - In the current study, we aimed to investigate the potential hypoglycemic
bioactivity of cinnamon extracts (CES) on streptozotocin (STZ)-induced
hyperglycemia in mice. In biological methods, glucose metabolic ability of all
mice was evaluated by glucose tolerance testing (GTT). Blood levels of pancreas
produced insulin, glucagon, inflammation-associated interleukin-6 (IL-6), tumor
necrosis factor-alpha (TNF-alpha) were determined via enzyme-linked immunosorbent
assay (ELISA). In gene level, intrapancreatic mRNA expressions of insulin, TNF
alpha and nuclear-factor kappa B (NF-kappaB) were assayed by reverse
transcription polymerase chain reaction (RT-PCR). Meanwhile, intracellular
insulin-immunoactive cells in the pancreas were analyzed by using
immunohistochemical staining. In addition, the protein levels of intrapancreatic
NF-kappaB, IkappaB (p-IkappaB) and IKK were tested by western blotting. As a
result, CES-treated mice showed increased body weight, blood glucose and insulin,
reduced IL-6 and TNF-alpha contents in sera. Further, the TNF-alpha and NF-kappaB
mRNA expressions in the CES-treated pancreas were down-regulated at a dose
dependent manner, while insulin mRNA was elevated. Moreover, the reduced
intrapancreatic NF-kappaB, IkappaB (p-IkappaB) and IKK expression were observed
in CES-treated pancreas, respectively. Taken together, our current findings
indicate that CES-mediated intrapancreatic cytoprotection is linked to the
molecular mechanism that may be through inhibiting inflammatory stress and
promoting insulin secretion in the pancreas.
PMID- 28694208
TI - Single nucleotide polymorphisms minisequencing in hypervariable regions for
screening of Thais.
AB - Mitochondrial DNA (mtDNA) analysis has displayed an important role and been
considered as a powerful tool in various fields of forensic science applications.
Nowadays, single nucleotide polymorphisms (SNPs) on mtDNA have become additional
DNA markers when conventional STR typing practically fails. mtDNA sequencing of
polymerase chain reaction (PCR) products from the hypervariable region I (HVRI)
and II (HVRII) is the standard method of mtDNA analysis. However, mtDNA
sequencing is rather expensive, time consuming and technically complex. This
study aims to develop the SNPs minisequencing for screening of Thai populations.
For this purpose, sixteen SNPs that possess high discriminating power in
hypervariable regions were selected. The DNA samples were obtained from 100
buccal swab samples of Thai healthy individuals. All DNA samples were extracted
and were subsequently amplified by single duplex PCR technique. The duplex PCR
products were genotyped by SNPs minisequencing. Based on 16 SNPs, a total of 63
haplotypes were observed of which 46 haplotypes were unique. The haplotype
diversity, discriminating power and random match probability were calculated to
be 0.9830, 0.9732 and 0.0268, respectively. The SNPs at 150, 199, 489, 16129,
16189, 16223, and 16304 were highly polymorphic in the studied population. Our
results suggested that the SNPs minisequencing can be an alternative method of
SNPs genotyping. This method can be used for an exclusion of a large number of
mismatch samples and as a presumptive test prior to do confirmatory mtDNA
sequencing.
PMID- 28694209
TI - Genome-wide identification and expression profiling of the SOX gene family in a
bivalve mollusc Patinopecten yessoensis.
AB - SOX family is composed of transcription factors that play vital roles in various
developmental processes. Comprehensive understanding on evolution of the SOX
family requires full characterization of SOX genes in different phyla. Mollusca
is the second largest metazoan phylum, but till now, systematic investigation on
the SOX family is still lacking in this phylum. In this study, we conducted
genome-wide identification of the SOX family in Yesso scallop Patinopecten
yessoensis and profiled their tissue distribution and temporal expression
patterns in the ovaries and testes during gametogenesis. Seven SOX genes were
identified, including SOXB1, B2, C, D, E, F and H, representing the first record
in protostomes with SOX members identical to that proposed to exist in the last
common ancestor of chordates. Genomic structure analysis identified relatively
conserved exon-intron structures, accompanied by intron insertion. Quantitative
real-time PCR analysis revealed possible involvement of scallop SOX in various
functions, including neuro-sensory cell differentiation, hematopoiesis,
myogenesis and gametogenesis. This study represents the first systematic
characterization of SOX gene family in Mollusca. It will assist in a better
understanding of the evolution and function of SOX family in metazoans.
PMID- 28694210
TI - Circulating microRNA expression as predictor of preeclampsia and its severity.
AB - Preeclampsia (PE) is a pregnancy syndrome characterized by hypertension and
proteinuria, and a leading cause of maternal and fetal morbidity and mortality,
with poorly defined pathophysiological mechanisms remain. Circulating microRNAs
(miRNAs) are small, noncoding RNA molecules, which negatively regulate gene
expression, and considered as promising biomarkers for PE. The objective of the
study was to evaluate circulating miRNA signatures in women with PE compared to
healthy women, and in women sub-grouped per PE severity. This study assessed
miRNA expression profile in the plasma of 15 women with PE (7 mild and 8 severe)
compared to 7 women with uncomplicated pregnancies. Circulating miRNA was
extracted from maternal plasma, and the differential expression of 84 miRNA
species were determined using customized pathway-focused miRNA profiler kits. A
set of 7 miRNAs that were differentially expressed in PE patients and in mild vs.
severe PE cases subgroups. These included miR-215, miR-155, miR-650, miR-210, miR
21 which were upregulated, and miR-18a, miR-19b1 were downregulated in women with
PE compared to control women, and between women with severe PE compared to mild
PE. In addition, four novel miRNAs comprising miR-518b and miR-29a which were
upregulated, and miR-144, miR-15b which were downregulated in severe PE compared
to mild PE. This study for the first time presents the differential expression
profile of circulating miRNAs according to the severity of the disease. The
results confirm the contribution of miRNA to PE pathogenesis, as well as being
predictors of the severity of PE.
PMID- 28694211
TI - Novel mutations in patients with hereditary red blood cell membrane disorders
using next-generation sequencing.
AB - To diagnose and investigate the genotype-phenotype relationship in intractable
hereditary red blood cell (RBC) membrane cases, we have utilized next-generation
sequencing (NGS) to develop a high-throughput, highly sensitive assay. Three
unrelated families including 15 individuals were analysed with a panel
interrogating 600 genes related to haematopathy disorders. Where possible,
inheritance patterns of pathogenic mutations were determined by sequencing the
relatives. We identified 2 novel mutations in ANK1 (Y216X and E142X) responsible
for hereditary spherocytosis (HS) that were stop-gain single nucleotide variants
(SNVs). Furthermore, a novel SPTA1 mutation (H54P) was identified; it is a
nonsynonymous SNV and is associated with hereditary elliptocytosis (HE). In
addition, patients who also carried erythropoiesis gene mutations showed more
severe disease phenotype. The NGS panel provides a fast and accurate method for
molecular diagnosis in patients with intractable hereditary RBC membrane
disorders. An approach integrating medical history, clinical and molecular
testing, and pedigree analysis is beneficial for these patients and families.
PMID- 28694212
TI - Role of rs13117307 single nuclear polymorphism in the risk of uterine cervical
cancer from Polish population and its impact on exocyst complex component 1
expression.
AB - We evaluated the role of NM_001024924.1:c.1330+1646C>T (rs13117307) single
nucleotide polymorphism (SNP), situated in the intronic region of exocyst complex
component 1 (EXCO1), in the development and spreading of cervical squamous cell
carcinoma (SCC). Utilizing high resolution melting curve analysis, we analyzed
this polymorphism in patients with cervical SCC (n=485) and controls (n=509) in
the Polish Caucasian population. Logistic regression analysis was used to adjust
for age, parity, oral contraceptive use, tobacco smoking, and menopausal status.
The influence of this polymorphism on the expression of EXCO1 was assessed by
reverse transcription and real-time quantitative PCR analysis. For all patients
with SCC, the p trend value calculated for rs13117307 was statistically
significant (ptrend=0.0158). The adjusted odds ratio (OR) for T/T vs. C/C was
1.434 (95 % CI 1.105-1.861, p=0.007). We also found a significant contribution of
rs13117307 to tumor stages III, IV and grade of differentiation G3. Other
contributors are parity, oral contraceptive use, smoking, and women of
postmenopausal age. We observed significant upregulation of EXCO1 transcript
levels in the non-cancerous cervical tissues in carriers of the T/T vs. C/C
(p=0.016), as well as an increase in the EXCO1 transcript levels in the cervical
SCC tissue in carriers of the T/T vs. C/C (p=0.029) and for T/T vs C/T
(p=0.0032). The rs13117307 SNP variants may upregulate the transcription of
EXCO1, as well as the risk of development and spreading of cervical SCC.
PMID- 28694213
TI - A general protocol of ultra-high resolution MR angiography to image the cerebro
vasculature in 6 different rats strains at high field.
AB - BACKGROUND: Differences in the cerebro-vasculature among strains as well as
individual animals might explain variability in animal models and thus, a non
invasive method tailored to image cerebral vessel of interest with high signal to
noise ratio is required. NEW METHOD: Experimentally, we describe a new general
protocol of three-dimensional time-of-flight magnetic resonance angiography to
visualize non-invasively the cerebral vasculature in 6 different rat strains.
Flow compensated angiograms of Sprague Dawley, Wistar Kyoto, Lister Hooded, Long
Evans, Fisher 344 and Spontaneous Hypertensive Rat strains were obtained without
the use of contrast agents. At 11.7T using a repetition time of 60ms, an
isotropic resolution of up to 62MUm was achieved; total imaging time was 98min
for a 3D data set. RESULTS: The visualization of the cerebral arteries was
improved by removing extra-cranial vessels prior to the calculation of maximum
intensity projection to obtain the angiograms. Ultimately, we demonstrate that
the newly implemented method is also suitable to obtain angiograms following
middle cerebral artery occlusion, despite the presence of intense vasogenic edema
24h after reperfusion. COMPARISON WITH EXISTING METHODS: The careful selection of
the excitation profile and repetition time at a higher static magnetic field
allowed an increase in spatial resolution to reliably detect of the hypothalamic
artery, the anterior choroidal artery as well as arterial branches of the peri
amygdoidal complex and the optical nerve in six different rat strains.
CONCLUSIONS: MR angiography without contrast agent can be utilized to study
cerebro-vascular abnormalities in various animal models.
PMID- 28694214
TI - Visualization of migration of human cortical neurons generated from induced
pluripotent stem cells.
AB - BACKGROUND: Neuronal migration is considered a key process in human brain
development. However, direct observation of migrating human cortical neurons in
the fetal brain is accompanied by ethical concerns and is a major obstacle in
investigating human cortical neuronal migration. NEW METHOD: We established a
novel system that enables direct visualization of migrating cortical neurons
generated from human induced pluripotent stem cells (hiPSCs). RESULTS: We
observed the migration of cortical neurons generated from hiPSCs derived from a
control and from a patient with lissencephaly. METHODS: Our system needs no
viable brain tissue, which is usually used in slice culture. Migratory behavior
of human cortical neuron can be observed more easily and more vividly by its
fluorescence and glial scaffold than that by earlier methods. CONCLUSIONS: Our in
vitro experimental system provides a new platform for investigating development
of the human central nervous system and brain malformation.
PMID- 28694215
TI - Fluorescein angiography findings in diffuse retinoblastoma: two case reports with
clinicopathologic correlation.
AB - Whereas most retinoblastomas are seen as intraocular tumors, the diffuse
infiltrating type is distinguished by a horizontal growth along the retina with
minimal vertical growth. These findings can resemble other entities and present
as a diagnostic challenge. Fluorescein angiography (FA) features of
retinoblastoma have been described in the literature; however, to our knowledge,
little information is available on the diffuse type. We present FA findings and
the clinicopathlogic correlation of 2 patients with diffuse retinoblastoma.
Changes observed on FA correlate with the vascular changes observed on
histopathology and can therefore be helpful in the diagnosis of atypical
retinoblastomas when the clinical presentation is equivocal.
PMID- 28694216
TI - An analysis of radiographic parameters comparison between lumbar spine
latericumbent and full-length lateral standing radiographs.
AB - BACKGROUND CONTEXT: The lumbar spine latericumbent and full-length lateral
standing radiographs are most commonly used to assess lumbar disorder. However,
there are few literatures on the difference and correlation of the sagittal
parameters between the two shooting positions. PURPOSE: The study aimed to
investigate the difference of sagittal parameters in spine lateral radiographs
between latericumbent and upright positions, identify the correlation, and
establish a preliminary linear fitting formula. STUDY DESIGN: The study is a
prospective study on radiographic evaluation of sagittal alignment using
latericumbent and upright positions. PATIENT SAMPLE: One hundred fifty-seven
patients were recruited from the orthopedics clinic of a single medical center.
OUTCOME MEASURE: Angle measurement, the intra- and interobserver measurement
reliability of measurement, and analysis of the angle measurement were carried
out. METHOD: The sagittal alignment of 157 patients were assessed using Surgimap
software from two kinds of lateral radiographs to acquire the following
parameters: lumbar lordosis (LL), pelvic incidence (PI), pelvic tilt (PT), sacral
slope (SS), L4-L5 intervertebral angle (IVA4-5), L4-L5 intervertebral height
index (IHI4-5), and PI-LL. The Kolmogorov-Smirnov test, paired t test, Pearson
correlation analysis, and multivariate linear regression analysis were used to
analyze the data. RESULTS: The results showed significantly statistical
difference in LL, SS, PT, IVA4-5, and PI-LL, except for PI and IHI4-5, between
the two positions. There was a significant relativity between standing LL and
latericumbent LL (r=0.733, p<.01), PI (r=0.611, p<.01), and SS (r=0.626, p<.01).
The predictive formula of standing LL was 12.791+0.777 latericumbent LL+0.395
latericumbent PI-0.506 latericumbent SS (adjusted R2=0.619, p<.05). CONCLUSION:
Not all of sagittal parameters obtained from two positions are identical. Thus,
the full-spine lateral standing films are difficult to be replaced. The surgeon
should give sufficient consideration to the difference between the two views. We
may primarily predict standing LL with the formula when we could not get whole
spine lateral standing radiographs.
PMID- 28694217
TI - The magnitude of angular and translational displacement of dens fractures is
dependent on the sagittal alignment of the cervical spine rather than the force
of injury.
AB - BACKGROUND CONTEXT: Although it is generally believed that the magnitude of dens
fracture displacement is proportional to the amount of force applied to the
cervical spine during injury, the factors responsible for displacement have not
been studied. PURPOSE: Our aim was to determine factors that contribute to
horizontal and angular displacement of dens fractures. STUDY DESIGN/SETTING: We
conducted a retrospective review of adult patients who were admitted to our level
1 trauma center between January 1, 2008 and December 31, 2013. PATIENT SAMPLE:
Angular and horizontal displacements of the fractured dens in 57 patients were
measured. Subjects were grouped based on mechanism of fracture: motor vehicle
accident, ground level fall, and higher falls. OUTCOME MEASURES: Cervical
lordosis was measured between C2 and T1. C3-C4, C4-C5, C5-C6, and C6-C7 disc
inclination angles were measured. Anteroposterior sagittal balance was assessed
by comparing the sagittal position of the C2 body with the C7 body. METHODS: Data
were analyzed using Pearson correlations, independent t tests, and support vector
regression to construct predictive models that determine factors contributing to
the angular and horizontal displacements. RESULTS: The mean horizontal
displacement of the fractured dens was not significantly different among groups.
However, the dens in those with ground level falls had a significantly greater
mean fracture angle compared with the higher energy trauma groups (p=.01). There
were positive correlations between angular displacement and C5-C6 disc space
inclination angle (r=0.67, p<.01) and C6-C7 disc space inclination angle (r=0.61,
p<.01). There were positive correlations between horizontal displacement and C6
C7 inclination angle (r=0.40, p<.01) and sagittal alignment (r=0.32, p<.01). The
predictive model using all variables demonstrated that angular fracture
displacement was only dependent on C5-C6 disc space inclination angle. Horizontal
displacement was only dependent on C6-C7 inclination angle and anteroposterior
sagittal balance. CONCLUSIONS: Disc space inclination angles of the lower
cervical spine and the cervical sagittal balance most contribute to the magnitude
of angular and horizontal displacement of the dens after fracture.
PMID- 28694218
TI - Constitutive expression of human gastric lipase in Pichia pastoris and site
directed mutagenesis of key lid-stabilizing residues.
AB - The cDNA encoding human gastric lipase (HGL) was integrated into the genome of
Pichia pastoris using the pGAPZalpha A transfer vector. The HGL signal peptide
was replaced by the yeast alpha-factor to achieve an efficient secretion. Active
rHGL was produced by the transformed yeast but its levels and stability were
dependent on the pH. The highest activity was obtained upon buffering the culture
medium at pH5, a condition that allowed preserving enzyme activity over time. A
large fraction (72+/-2%) of secreted rHGL remained however bound to the yeast
cells, and was released by washing the cell pellet with an acid glycine-HCl
buffer (pH2.2). This procedure allowed establishing a first step of purification
that was completed by size exclusion chromatography. N-terminal sequencing and
MALDI-ToF mass spectrometry revealed that rHGL was produced in its mature form,
with a global mass of 50,837+/-32Da corresponding to a N-glycosylated form of HGL
polypeptide (43,193Da). rHGL activity was characterized as a function of pH,
various substrates and in the presence of bile salts and pepsin, and was found
similar to native HGL, except for slight changes in pH optima. We then studied by
site-directed mutagenesis the role of three key residues (K4, E225, R229)
involved in salt bridges stabilizing the lid domain that controls the access to
the active site and is part of the interfacial recognition site. Their
substitution has an impact on the pH-dependent activity of rHGL and its relative
activities on medium and long chain triglycerides.
PMID- 28694219
TI - Hepatic ABCA1 deficiency is associated with delayed apolipoprotein B secretory
trafficking and augmented VLDL triglyceride secretion.
AB - ATP binding cassette transporter A1 (ABCA1) is a membrane transporter that
facilitates nascent HDL formation. Tangier disease subjects with complete ABCA1
deficiency have <5% of normal levels of plasma HDL, elevated triglycerides (TGs),
and defective vesicular trafficking in fibroblasts and macrophages. Hepatocyte
specific ABCA1 knockout mice (HSKO) have a similar lipid phenotype with 20% of
normal plasma HDL levels and a two-fold elevation of plasma TGs due to hepatic
overproduction of large, triglyceride-enriched VLDL. We hypothesized that
enhanced VLDL TG secretion in the absence of hepatocyte ABCA1 is due to altered
intracellular trafficking of apolipoprotein B (apoB), resulting in augmented TG
addition to nascent VLDL. We found that trafficking of newly synthesized apoB
through the secretory pathway was delayed in ABCA1-silenced rat hepatoma cells
and HSKO primary hepatocytes, relative to controls. Endoglycosidase H treatment
of cellular apoB revealed a likely delay in apoB trafficking in post-ER
compartments. The reduced rate of protein trafficking was also observed for an
adenoviral-expressed GPI-linked fluorescent fusion protein, but not albumin,
suggesting a selective delay of secretory cargoes in the absence of hepatocyte
ABCA1. Our results suggest an important role for hepatic ABCA1 in regulating
secretory trafficking and modulating VLDL expansion during the TG accretion phase
of hepatic lipoprotein particle assembly.
PMID- 28694220
TI - Failed Removal of Indwelling Urinary Catheters in Patients With Acute Stroke:
Incidence and Risk Factors.
AB - BACKGROUND: Reducing the incidence of indwelling urinary catheter (IUC) use and
early removal of the devices that are inserted are appropriate priorities for
quality patient care. Just like symptomatic bacteriuria, failed catheter removal
as a complication of IUC use is associated with considerable morbidity. In the
ideal setting, patients who need IUCs have them, and patients who do not need
them will have them removed safely, with the goal of reducing medical
complications and facilitating the rehabilitation phase of care. OBJECTIVE: To
determine the incidence of failed removal of IUCs and the factors associated with
failed removal in persons hospitalized with acute stroke. DESIGN: Retrospective
review of medical records and associated clinical data collection platforms.
SETTING: Comprehensive stroke center at a tertiary care hospital. PATIENTS: The
study cohort included 175 stroke patients admitted to the hospital and managed
with IUCs. Mean age was 66.1 years (standard deviation = 15), 55% were female.
METHODS: Univariable and multiple logistic regression analyses were performed.
Variables assessed included age, gender, race, duration of hospital stay, stroke
subtype, National Institutes of Health Stroke Scale, and 6-Clicks Scale, which is
a measure of functional status. MAIN OUTCOME MEASUREMENTS: The dependent variable
was occurrence of a failed attempt at removal of an IUC, defined as removal
followed by a catheter reinsertion. RESULTS: During the study period, 175 of 432
patients with acute hospital admission for new stroke had an IUC removal event.
Of these patients, 46 (26%) experienced a failed catheter removal. On univariate
analysis, factors significantly associated with failed removal included presence
of a hemorrhagic stroke (P = .005), lower level of physical function (by 6-Clicks
and NIHSS scores), hospital length of stay (P < .001), and discharge location (P
= .005). Bedside bladder ultrasound testing by nursing staff was used more
frequently in the group of patients who had unsuccessful IUC removals (95%
confidence interval 4.56-21.67, P < .001). Length of stay (P < .001), white race
(P = .001), and hemorrhagic stroke (P = .009) were associated independently with
failed catheter removal after adjustment for other clinical variables.
CONCLUSIONS: This single-site study identified a high incidence of failed urinary
catheter removal in patients with stroke, along with factors associated with
failed removal. This is the first step in developing a predictive model that
could reduce the incidence of this adverse event. Policies, penalties, and
protocols designed to reduce catheter days must be sensitive to the special
situations in which IUCs are medically necessary and equal consideration given to
identifying the patients for which catheter removal poses a greater risk than
continued catheter use. LEVEL OF EVIDENCE: III.
PMID- 28694221
TI - Nordic Walking for the Management of People With Parkinson Disease: A Systematic
Review.
AB - BACKGROUND: It is well known that physical exercise is the main therapeutic
element of rehabilitation programs for people with Parkinson disease (PD). As
traditional forms of exercise can guarantee significant health benefits, the
emergence of nonconventional physical activities, such as Nordic walking (NW),
may add positive effects. OBJECTIVE: To appraise the available evidence on the
main effects of NW in the rehabilitation programs for people with PD and to
propose a design for upcoming research that might improve the uniformity of
future trials. STUDY DESIGN: Systematic review. LITERATURE SURVEY: A literature
search of 5 established databases (PubMed, MEDLINE, Scopus, Web of Science, and
Cochrane) was conducted. METHODOLOGY: Any relevant randomized controlled trials
pertinent to NW in PD published in English from inception to February 2017 were
included. Preferred Reporting Items for Systematic Reviews and Meta-Analyses
guidelines were followed, and the methodologic quality of each study was assessed
by the Physiotherapy Evidence Database scale. DATA SYNTHESIS: Sixty-six studies
were retrieved, and 6 randomized controlled trials (221 subjects) were entered
into the qualitative synthesis. Overall, these studies portrayed NW as feasible
and likely to be effective in improving the functional and clinical outcomes of
people with PD. When we compared NW with other exercise-based interventions, such
as treadmill training, free walking, a program of standardized whole-body
movements with maximal amplitude (Lee Silverman Voice Treatment BIG training), or
a home-based exercise program, the findings proved controversial. CONCLUSIONS:
High heterogeneity and methodologic discrepancies among the studies prevent us
from drawing firm conclusions on the effectiveness of NW in comparison with other
exercise-based interventions currently used by people with PD. Further
investigations with a common design are necessary to verify whether NW may be
included within conventional rehabilitation programs commonly recommended to
people with PD. LEVEL OF EVIDENCE: II.
PMID- 28694222
TI - Effects of single genetic variants and polygenic obesity risk scores on
disordered eating in adolescents - The HUNT study.
AB - PURPOSE: Improving the understanding of the role of genetic risk on disordered
eating (DE). METHODS: A case-control study including 1757 (F: 979, M: 778)
adolescents (aged 13-19 years) from the Nord-Trondelag Health Study (HUNT), an
ethnically homogenous Norwegian population based study. Cases and controls were
defined using a shortened version of the Eating Attitude Test. Logistic
regression was employed to test for associations between DE phenotypes and 24
obesity and eating disorder susceptibility SNPs, and the joint effect of a subset
of these in a genetic risk score (GRS). RESULTS: COMT was shown to be associated
with poor appetite/undereating (OR: 0.6, CI 95%: 0.43-0.83, p = 0.002).
Independent of obesity associations, the weighted GRS was associated to
overeating in 13-15 year old females (OR: 2.07, CI 95%: 1.14-3.76, p = 0.017).
Additionally, a significant association was observed between the GRS and loss of
control over eating in the total sample (OR: 1.62, CI 95%: 1.01-2.61, p = 0.046).
CONCLUSIONS: The COMT variant (rs4680) was associated with poor
appetite/undereating. Our study further confirms prior findings that obesity risk
also confers risk for loss of control over eating; and overeating amongst girls.
PMID- 28694223
TI - "It's not as easy as saying, 'just get them to eat more veggies'": Exploring
healthy eating in residential care in Australia.
AB - Young people living in residential out-of-home care (henceforth OoHC) are at
increased risk of becoming overweight or obese. Currently, recognition of the
everyday mechanisms that might be contributing to excess weight for children and
young people in this setting is limited. The aim of this study was to better
understand the barriers and complexities involved in the provision of a 'healthy'
food environment in residential OoHC. Heightening awareness of these factors and
how they might compromise a young person's physical health, will inform the
development, refinement and evaluation of more sensitive and tailored weight
related interventions for this population. The paper presents a nuanced picture
of the complexity of everyday food routines in residential care, and illustrates
the ways in which food is 'done' in care; how food can be both symbolic of care
but also used to exercise control; the way in which food can be used to create a
'family-like' environment; and the impact of traumatic experiences in childhood
on subsequent behaviours and overall functioning in relation to food. It is
argued that a health agenda designed for a mainstream population ignores the very
complex relationship that children in residential OoHC may have with food. It is
recommended that future intervention approaches account for personal food
biographies, trauma and children's social backgrounds and how these are
implicated in everyday practices and interactions around food.
PMID- 28694224
TI - From universal postoperative pain recommendations to procedure-specific pain
management.
PMID- 28694225
TI - Dynamic arterial elastance obtained using arterial signal does not predict an
increase in arterial pressure after a volume expansion in the operating room.
AB - INTRODUCTION: Dynamic arterial elastance (Eadyn) is defined as the ratio between
pulse pressure variations (PPV) and stroke volume variations (SVV). Eadyn has
been proposed to predict an increase in mean arterial pressure (MAP) after volume
expansion with conflicting results. The aim of the present study was to test the
reliability of Eadyn in hypotensive patients (MAP<65mmHg) in the operating room
(OR). PATIENTS AND METHODS: The study pooled data from 51 patients. They were
included after the induction of anaesthesia and before skin incision. Eadyn, MAP
and stroke volume (FloTracTM, VigileoTM, Edwards Lifesciences, Irvine,CA) were
recorded before and after volume expansion (500mL starch 6% given over
10minutes). Pressure-responders were defined as an increase MAP>=15% after volume
expansion. Changes in MAP were predicted using the area under the curves (AUC)
with their 95% Confidence Interval (95%CI) derived from Receiver Operating
Characteristic curves. RESULTS: Seventeen patients responded to volume expansion.
Heart rate, PPV, SVV and Eadyn were similar between pressure-responders and non
responders. Baseline values of stroke volume, cardiac output and MAP were lower
in responders. Volume expansion induced significant variations in stroke volume,
cardiac output, SVV and PPV, but not in Eadyn. Baseline Eadyn failed to predict
MAP increase (AUC=0.53, 95%CI=0.36-0.70, P>0.05) and was not correlated with
volume expansion-induced changes in MAP (P>0.05). In preload responsive patients
(changes in SV>=15% after volume expansion, n=24), the AUC was 0.54 (95%CI=0.29
0.78; P>0.05). CONCLUSION: In the present study performed in the OR and in
hypotensive patients, Eadyn obtained using arterial signal was unable to predict
an increase in MAP after volume expansion.
PMID- 28694226
TI - Repeated failure with regional blocks: Technical problem or resistance to local
anaesthetics?
PMID- 28694227
TI - Management of a cardiac shock in an austere military environment (Northern
Niger).
PMID- 28694228
TI - Impact factor: An assessment tool for journals or for scientists?
PMID- 28694229
TI - Motor expertise modulates neural oscillations and temporal dynamics of cognitive
control.
AB - The field of motor expertise in athletes has recently been receiving increasing
levels of investigation. However, there has been less investigation of how
dynamic changes in behavior and in neural activity as a result of sporting
participation might result in superiority for athletes in domain-general
cognition. We used a flanker task to investigate conflict-related behavioral
measures, such as mean reaction time (RT) and RT variability, in conjunction with
electroencephalographic (EEG) measures, including N2d, theta activity power, and
inter-trial phase coherence (ITPC). These measures were compared for 18 badminton
players, an interceptive sport requiring the performance of skills in a fast
changing and unpredictable environment, and 18 athletic controls (14 track-and
field athletes and 4 dragon boat athletes), with high fitness levels but no
requirement for skills such as responses to their opponents. Results showed that
badminton players made faster and less variable responses on the flanker task
than athletic controls, regardless of stimulus congruency levels. For EEG
measures, both badminton players and athletic controls showed comparable
modulations of conflicting on midfrontal N2 and theta power. However, such an
effect on ITPC values was found only for the badminton players. The behavior-EEG
correlation seen suggests that smaller changes in RT variability induced by
conflicting process in badminton players may be attributable to greater stability
in the neural processes in these individuals. Because these findings were
independent from aerobic fitness levels, it seems such differences are likely due
to training-induced adaptations, consistent with the idea of specific transfer
from cognitive components involved in sport training to domain-general cognition.
PMID- 28694230
TI - Pharmacokinetics of piperacillin-tazobactam in plasma, peritoneal fluid and
peritoneum of surgery patients, and dosing considerations based on site-specific
pharmacodynamic target attainment.
AB - Piperacillin-tazobactam (PIP-TAZ) is commonly used to treat intraabdominal
infections; however, its penetration into abdominal sites is unclear. A
pharmacokinetic analysis of plasma, peritoneal fluid, and peritoneum drug
concentrations was conducted to simulate dosing regimens needed to attain the
pharmacodynamic target in abdominal sites. PIP-TAZ (4 g-0.5 g) was intravenously
administered to 10 patients before abdominal surgery for inflammatory bowel
disease. Blood, peritoneal fluid, and peritoneum samples were obtained at the end
of infusion (0.5 h) and up to 4 h thereafter. PIP and TAZ concentrations were
measured, both noncompartmental and compartmental pharmacokinetic parameters were
estimated, and a simulation was conducted to evaluate site-specific
pharmacodynamic target attainment. The mean peritoneal fluid:plasma ratios in the
area under the drug concentration-time curve (AUC) were 0.75 for PIP and 0.79 for
TAZ, and the mean peritoneal fluid:plasma ratios in the AUC were 0.49 for PIP and
0.53 for TAZ. The mean PIP:TAZ ratio was 8.1 at both peritoneal sites. The
regimens that achieved a bactericidal effect with PIP (time above minimum
inhibitory concentration [MIC] >50%) at both peritoneal sites were PIP-TAZ 4.5 g
twice daily for an MIC of 8 mg/L, as well as 4.5 g three times daily, and 3.375 g
four times daily for an MIC of 16 mg/L. These findings clarify the peritoneal
pharmacokinetics of PIP-TAZ, and help consider the dosing regimens for
intraabdominal infections based on site-specific pharmacodynamic target
attainment.
PMID- 28694231
TI - Repurposing Ivacaftor for treatment of Staphylococcus aureus infections.
AB - Drug repurposing of non-antimicrobials is a novel method to augment a seriously
depleted drug pipeline for targeting drug-resistant pathogens. This article
highlights the potent antimicrobial activity of Ivacaftor against Staphylococcus
aureus, including vancomycin- and other multidrug-resistant strains. The potent
activity of Ivacaftor in vivo is also demonstrated in a murine neutropenic thigh
infection model. Taken together, these results support the potential of Ivacaftor
as an antimicrobial agent for the treatment of staphylococcal infections.
PMID- 28694232
TI - Reinforcement of an antimicrobial stewardship task force aims at a better use of
antibiotics of last resort: the COLITIFOS study.
AB - BACKGROUND: Physicians are facing a worldwide increase in multidrug-resistant
(MDR) organisms. Eradication of such bacteria, including so called superbugs
(XDR), may cause physicians to prescribe last-resort antibiotics. However,
experience with these drugs is limited and few data are available. METHODS: A
before and after retrospective study was conducted from January 2008 to June
2016. Prescriptions of parenteral antimicrobials considered as last-resort
antibiotics (colistin, fosfomycin, tigecycline and temocillin) were reviewed by 4
infectious disease specialists (according to microbiology results, susceptibility
testing, clinical situation and alternative agents), while doses were analysed by
a pharmacist. As a second step, the cohort was split before and after 2013
coinciding with the arrival of a referent in antimicrobial stewardship. RESULTS:
The treatment of 77 patients with a mean age of 55.4 +/- 18.7 years was analysed.
The majority were treated for gram-negative rods (69.2%), especially Pseudomonas
and Klebsiella spp. and Escherichia coli while 20.0% of patients were treated for
gram-positive cocci (mainly Staphylococcus aureus) and the remainder were
polymicrobial. Of 84 prescriptions, fosfomycin was the most frequently prescribed
(47.6%), followed by colistin (40.5%), tigecycline (10.7%) and temocillin (1.2%).
Outcomes were favorable in 75.3% of patients. In patients with MDR and XDR
infections (n = 54), the mortality rate was 11.1%. After 2013, there were
significantly fewer prescriptions of last-resort antibiotics for susceptible
microorganisms (29.2% vs 6.9%), in the absence of supporting microbiology results
(22.9% vs 3.5%) and fewer dose errors (56.2% vs 27.6%) (P = 0.02). CONCLUSION:
Reinforcement of the antimicrobial stewardship task force seems to be valuable
for promoting the better use of last-resort antibiotics.
PMID- 28694233
TI - Comparing the safety and efficacy of voriconazole versus posaconazole in the
prevention of invasive fungal infections in high-risk patients with hematological
malignancies.
AB - Invasive fungal infection (IFI) is a leading cause of morbidity and mortality in
immunocompromised cancer patients. New triazole-based antifungal agents have been
recommended for IFI prophylaxis in these patients. This retrospective study
compared the safety and efficacy of voriconazole and posaconazole as prophylaxis
in patients with hematological malignancies (HM), who were admitted to The
University of Texas MD Anderson Cancer Center between January 2014 and August
2015, and who were started on single antifungal prophylaxis consisting of either
voriconazole or posaconazole. A total of 200 patients with hematological
malignancy were evaluated, the majority of whom had acute myeloid leukemia (AML)
(67%). Baseline characteristics, including malignancy status and neutropenia
status, were comparable in the two groups. The duration of prophylaxis was
similar in the two groups, with medians of 46 days for voriconazole and 48 days
for posaconazole. There was no significant difference in breakthrough IFIs
between the two groups (3% vs. 0%, P = 0.25). Adverse events occurred in 65% of
the voriconazole group vs. 78% of the posaconazole group (P = 0.08). Symptomatic
adverse events were more common for voriconazole than for posaconazole (6% vs.
0%, P = 0.03). Eleven patients discontinued voriconazole and seven patients
discontinued posaconazole due to adverse events. All-cause mortality was similar
in the two groups. Both agents were effective in preventing IFI in hematological
malignancy, with comparable all-cause mortality rates. Symptomatic adverse events
were significantly more common in the voriconazole group, whereas liver function
test abnormality was more common in the posaconazole group.
PMID- 28694234
TI - Effectiveness of and obstacles to antibiotic streamlining to amoxicillin
monotherapy in bacteremic pneumococcal pneumonia.
AB - BACKGROUND: Antibiotic streamlining is pivotal to reduce the emergence of
resistant bacteria. However, whether streamlining is frequently performed and
safe in difficult situations, such as bacteremic pneumococcal pneumonia (BPP),
has still to be assessed. METHODS: All adult patients admitted to Dijon Hospital
(France) from 2005 to 2013 who had BPP without complications, and were alive on
the third day were enrolled. Clinical, biological, radiological, microbiological
and therapeutic data were recorded. A first analysis was conducted to assess
factors associated with being on amoxicillin on the third day. A second analysis,
adjusting for a propensity score, was performed to determine whether 30-day
mortality was associated with streamlining to amoxicillin monotherapy. RESULTS:
Of the 196 patients hospitalized for BPP, 161 were still alive on the third day
and were included in the study. Treatment was streamlined to amoxicillin in 60
patients (37%). Factors associated with not streamlining were severe pneumonia
(OR 3.11, 95%CI [1.23-7.87]) and a first-line antibiotic combination (OR 3.08,
95%CI [1.34-7.09]). By contrast, starting with amoxicillin monotherapy correlated
inversely with the risk of subsequent treatment with antibiotics other than
amoxicillin (OR 0.06, 95%CI [0.01-0.30]). The Cox model adjusted for the
propensity-score analysis showed that streamlining to amoxicillin during BPP was
not significantly associated with a higher risk of 30-day mortality (HR 0.38,
95%CI [0.08-1.87]). CONCLUSIONS: Streamlining to amoxicillin is insufficiently
implemented during BPP. This strategy is safe and potentially associated with
ecological and economic benefits; therefore, it should be further encouraged,
particularly when antibiotic combinations are started for severe pneumonia.
PMID- 28694235
TI - Clinical benefits of antimicrobial de-escalation in adults with community-onset
monomicrobial Escherichia coli, Klebsiella species and Proteus mirabilis
bacteremia.
AB - The clinical benefits of an antimicrobial de-escalation strategy were compared
with those of a no-switch strategy in bacteremic patients. Adults with community
onset monomicrobial Escherichia coli, Klebsiella species and Proteus mirabilis
bacteremia treated empirically using broad-spectrum beta-lactams, including third
generation cephalosporins (GCs), fourth-GC or carbapenems, were treated
definitively with first- or second-GCs (de-escalation group), the same regimens
as empirical antibiotics (no-switch group), or antibiotics with a broader
spectrum than empirical antibiotics (escalation group). The eligible 454 adults
were categorized as the de-escalation (231 patients, 50.9%), no-switch (177,
39.0%), and escalation (46, 10.1%) groups. Patients with de-escalation therapy
were more often female, had less critical illness and fatal comorbidity, and had
a higher survival rate than patients in the other two groups. After propensity
score matching in the de-escalation and no-switch groups, critical illness at
onset (Pitt bacteremia score >= 4; 16.5% vs. 12.7%; P = 0.34) or day 3 (2.5% vs.
2.5%; P = 1.00), fatal comorbidity (16.5% vs. 21.5%; P = 0.25), time to
defervescence (4.6 vs. 4.7 days; P = 0.89), hospital stays (11.5 vs. 10.3 days; P
= 0.13) and 4-week crude mortality rate (4.4% vs. 4.4%; P = 1.00) were similar.
However, lower antibiotic cost (mean: 212.1 vs. 395.6 US$, P <0.001) and fewer
complications of bloodstream infections due to resistant pathogens (0% vs. 5.1%,
P = 0.004) were observed in the de-escalation group. De-escalation to narrower
spectrum cephalosporins is safe and cost-effective for adults with community
onset EKP bacteremia stabilized by empirical broad-spectrum beta-lactams.
PMID- 28694236
TI - Fibrin functionalization with synthetic adhesive ligands interacting with
alpha6beta1 integrin receptor enhance neurite outgrowth of embryonic stem cell
derived neural stem/progenitors.
AB - : To enhance fibrin hydrogel affinity towards pluripotent stem cell-derived
neural stem/progenitor cells (NSPCs) and its capacity to support NSPC migration
and neurite extension, we explored the tethering of synthetic peptides engaging
integrin alpha6beta1, a cell receptor enriched in NSPCs. Six alpha6beta1 integrin
ligands were tested for their ability to support integrin alpha6beta1-mediated
adhesion of embryonic stem cell-derived NSPCs (ES-NSPs) and sustain ES-NSPC
viability, migration, and neuronal differentiation. Due to their better
performance, peptides T1, HYD1, and A5G81 were immobilized into fibrin and
functionalized gels characterized in terms of peptide binding efficiency,
structure and viscoelastic properties. Tethering of T1 or HYD1 successfully
enhanced cell outgrowth from ES-NSPC neurospheres (up to 2.4-fold increase),
which exhibited a biphasic response to peptide concentration. Inhibition assays
evidenced the involvement of alpha6beta1 and alpha3beta1 integrins in mediating
radial outgrowth on T1-/HYD1-functionalized gels. Fibrin functionalization also
promoted neurite extension of single ES-NSPCs in fibrin, without affecting cell
proliferation and neuronal differentiation. Finally, HYD1-functionalized gels
were found to provide a permissive environment for axonal regeneration, leading
up to a 2.0-fold increase in neurite extension from rat dorsal root ganglia
explants as compared to unmodified fibrin, and to significant improved locomotor
function after spinal cord injury (complete transection), along with a trend
toward a higher area positive for growth associated protein 43 (marker for axonal
growth cone formation). Our results suggest that conjugation of alpha6beta1
integrin-binding motifs is of interest to increase the biofunctionality of
hydrogels used in 3D platforms for ES-NSPC culture and potentially, in matrix
assisted ES-NSPC transplantation. STATEMENT OF SIGNIFICANCE: Impact statement:
The transplantation of NSPCs derived from pluripotent stem cells holds much
promise for the treatment of central nervous system disorders. Moreover, the
combinatorial use of biodegradable hydrogels with NSPCs was shown to contribute
to the establishment of a more permissive environment for survival and
integration of transplanted cells. In this study, fibrin hydrogels functionalized
with a synthetic peptide engaging integrin alpha6beta1 (HYD1) were shown to
promote neurite extension of ES-NSPCs, which is fundamental for the formation of
functional neuronal relay circuits after NSPC transplantation. Notably, HYD1
functionalized fibrin per se led to enhanced axonal growth ex vivo and to an
improvement in locomotor function after implantation in a rat model of spinal
cord injury. Conjugation of alpha6beta1 integrin-binding motifs may therefore be
of interest to confer bioactivity to NSPC hydrogel vehicles.
PMID- 28694237
TI - Phase transitions during compression and decompression of clots from platelet
poor plasma, platelet-rich plasma and whole blood.
AB - : Blood clots are required to stem bleeding and are subject to a variety of
stresses, but they can also block blood vessels and cause heart attacks and
ischemic strokes. We measured the compressive response of human platelet-poor
plasma (PPP) clots, platelet-rich plasma (PRP) clots and whole blood clots and
correlated these measurements with confocal and scanning electron microscopy to
track changes in clot structure. Stress-strain curves revealed four
characteristic regions, for compression-decompression: (1) linear elastic region;
(2) upper plateau or softening region; (3) non-linear elastic region or re
stretching of the network; (4) lower plateau in which dissociation of some newly
made connections occurs. Our experiments revealed that compression proceeds by
the passage of a phase boundary through the clot separating rarefied and
densified phases. This observation motivates a model of fibrin mechanics based on
the continuum theory of phase transitions, which accounts for the pre-stress
caused by platelets, the adhesion of fibrin fibers in the densified phase, the
compression of red blood cells (RBCs), and the pumping of liquids through the
clot during compression/decompression. Our experiments and theory provide
insights into the mechanical behavior of blood clots that could have implications
clinically and in the design of fibrin-based biomaterials. STATEMENT OF
SIGNIFICANCE: The objective of this paper is to measure and mathematically model
the compression behavior of various human blood clots. We show by a combination
of confocal and scanning electron microscopy that compression proceeds by the
passage of a front through the sample that separates a densified region of the
clot from a rarefied region, and that the compression/decompression response is
reversible with hysteresis. These observations form the basis of a model for the
compression response of clots based on the continuum theory of phase transitions.
Our studies may reveal how clot rheology under large compression in vivo due to
muscle contraction, platelet retraction and hydrodynamic flow varies under
various pathophysiological conditions and could inform the design of fibrin based
biomaterials.
PMID- 28694238
TI - Functionalized bioengineered spider silk spheres improve nuclease resistance and
activity of oligonucleotide therapeutics providing a strategy for cancer
treatment.
AB - : Cell-selective delivery and sensitivity to serum nucleases remain major hurdles
to the clinical application of RNA-based oligonucleotide therapeutics, such as
siRNA. Spider silk shows great potential as a biomaterial due to its
biocompatibility and biodegradability. Self-assembling properties of silk
proteins allow for processing into several different morphologies such as fibers,
scaffolds, films, hydrogels, capsules and spheres. Moreover, bioengineering of
spider silk protein sequences can functionalize silk by adding peptide moieties
with specific features including binding or cell recognition domains. We
demonstrated that modification of silk protein by adding the nucleic acid binding
domain enabled the development of a novel oligonucleotide delivery system that
can be utilized to improve pharmacokinetics of RNA-based therapeutics, such as
CpG-siRNA. The MS2 bioengineered silk was functionalized with poly-lysine domain
(KN) to generate hybrid silk MS2KN. CpG-siRNA efficiently bound to MS2KN in
contrary to control MS2. Both MS2KN complexes and spheres protected CpG-siRNA
from degradation by serum nucleases. CpG-siRNA molecules encapsulated into MS2KN
spheres were efficiently internalized and processed by TLR9-positive macrophages.
Importantly, CpG-STAT3siRNA loaded in silk spheres showed delayed and extended
target gene silencing compared to naked oligonucleotides. The prolonged Stat3
silencing resulted in the more pronounced downregulation of interleukin 6 (IL-6),
a proinflammatory cytokine and upstream activator of STAT3, which limits the
efficacy of TLR9 immunostimulation. Our results demonstrate the feasibility of
using spider silk spheres as a carrier of therapeutic nucleic acids. Moreover,
the modified kinetic and activity of the CpG-STAT3siRNA embedded into silk
spheres is likely to improve immunotherapeutic effects in vivo. STATEMENT OF
SIGNIFICANCE: We demonstrated that modification of silk protein by adding the
nucleic acid binding domain enabled the development of a novel oligonucleotide
delivery system that can be utilized to improve pharmacokinetics of RNA-based
therapeutics. Although, the siRNA constructs have already given very promising
results in the cancer therapy, the in vivo application of RNA-based
oligonucleotide therapeutics still is limited due to their sensitivity to serum
nucleases and some toxicity. We propose a carrier for RNA-based therapeutics that
is made of bioengineered spider silk. We showed that functionalized bioengineered
spider silk spheres not only protected RNA-based therapeutics from degradation by
serum nucleases, but what is more important the embedding of siRNA into silk
spheres delayed and extended target gene silencing compared with naked
oligonucleotides. Moreover, we showed that plain silk spheres did not have
unspecific effect on target gene levels proving not only to be non-cytotoxic but
also very neutral vehicles in terms of TLR9/STAT3 activation in macrophages. We
demonstrated advantages of novel delivery technology in safety and efficacy
comparing with delivery of naked CpG-STAT3siRNA therapeutics.
PMID- 28694239
TI - Assessing Suicide Risk and Emotional Distress in Chinese Social Media: A Text
Mining and Machine Learning Study.
AB - BACKGROUND: Early identification and intervention are imperative for suicide
prevention. However, at-risk people often neither seek help nor take professional
assessment. A tool to automatically assess their risk levels in natural settings
can increase the opportunity for early intervention. OBJECTIVE: The aim of this
study was to explore whether computerized language analysis methods can be
utilized to assess one's suicide risk and emotional distress in Chinese social
media. METHODS: A Web-based survey of Chinese social media (ie, Weibo) users was
conducted to measure their suicide risk factors including suicide probability,
Weibo suicide communication (WSC), depression, anxiety, and stress levels.
Participants' Weibo posts published in the public domain were also downloaded
with their consent. The Weibo posts were parsed and fitted into Simplified
Chinese-Linguistic Inquiry and Word Count (SC-LIWC) categories. The associations
between SC-LIWC features and the 5 suicide risk factors were examined by logistic
regression. Furthermore, the support vector machine (SVM) model was applied based
on the language features to automatically classify whether a Weibo user exhibited
any of the 5 risk factors. RESULTS: A total of 974 Weibo users participated in
the survey. Those with high suicide probability were marked by a higher usage of
pronoun (odds ratio, OR=1.18, P=.001), prepend words (OR=1.49, P=.02),
multifunction words (OR=1.12, P=.04), a lower usage of verb (OR=0.78, P<.001),
and a greater total word count (OR=1.007, P=.008). Second-person plural was
positively associated with severe depression (OR=8.36, P=.01) and stress (OR=11,
P=.005), whereas work-related words were negatively associated with WSC (OR=0.71,
P=.008), severe depression (OR=0.56, P=.005), and anxiety (OR=0.77, P=.02).
Inconsistently, third-person plural was found to be negatively associated with
WSC (OR=0.02, P=.047) but positively with severe stress (OR=41.3, P=.04).
Achievement-related words were positively associated with depression (OR=1.68,
P=.003), whereas health- (OR=2.36, P=.004) and death-related (OR=2.60, P=.01)
words positively associated with stress. The machine classifiers did not achieve
satisfying performance in the full sample set but could classify high suicide
probability (area under the curve, AUC=0.61, P=.04) and severe anxiety (AUC=0.75,
P<.001) among those who have exhibited WSC. CONCLUSIONS: SC-LIWC is useful to
examine language markers of suicide risk and emotional distress in Chinese social
media and can identify characteristics different from previous findings in the
English literature. Some findings are leading to new hypotheses for future
verification. Machine classifiers based on SC-LIWC features are promising but
still require further optimization for application in real life.
PMID- 28694240
TI - Feasibility of Establishing HIV Case-Based Surveillance to Measure Progress Along
the Health Sector Cascade: Situational Assessments in Tanzania, South Africa, and
Kenya.
AB - BACKGROUND: To track the HIV epidemic and responses to it, the World Health
Organization recommends 10 global indicators to collect information along the HIV
care cascade. Patient diagnosis and medical record data, harnessed through case
based surveillance (CBS), can be used to measure 8 of these. While many high
burden countries have well-established systems for monitoring patients on HIV
treatment, few have formally adopted CBS. OBJECTIVE: In response to the need for
improved strategic HIV information and to facilitate the development of CBS in
resource-limited countries, we aimed to conduct situational assessments of
existing data collection systems in Tanzania, South Africa, and Kenya. METHODS:
We developed a standardized protocol and a modularized data collection tool to be
adapted for the particular focus of the assessments within each country. The
three countries were selected based on their stage of readiness for CBS. The
assessment included three parts: a desk review of relevant materials on HIV
surveillance and program monitoring, stakeholder meetings, and site visits.
RESULTS: In all three countries, routine HIV program monitoring is conducted, and
information on new HIV diagnoses and persons accessing HIV care and treatment
services is collected. Key findings from the assessments included substantial
stakeholder support for the development of CBS, significant challenges in linking
data within and between systems, data quality, the ability to obtain data from
multiple sources, and information technology infrastructure. Viral load testing
capacity varied by country, and vital registry data were not routinely linked to
health systems to update medical records. CONCLUSIONS: Our findings support the
development of CBS systems to systematically capture routinely collected health
data to measure and monitor HIV epidemics and guide responses. Although there
were wide variations in the systems examined, some of the current program and
patient monitoring systems can be adapted to function effectively for CBS,
especially if supported by an improved patient registration system with shared
unique health identifiers.
PMID- 28694241
TI - Controlling Your "App"etite: How Diet and Nutrition-Related Mobile Apps Lead to
Behavior Change.
AB - BACKGROUND: In recent years, obesity has become a serious public health crisis in
the United States. Although the problem of obesity is being addressed through a
variety of strategies, the use of mobile apps is a relatively new development
that could prove useful in helping people to develop healthy dietary habits.
Though such apps might lead to health behavior change, especially when relevant
behavior change theory constructs are integrated into them, the mechanisms by
which these apps facilitate behavior change are largely unknown. OBJECTIVE: The
purpose of this study was to identify which behavior change mechanisms are
associated with the use of diet- and nutrition-related health apps and whether
the use of diet- and nutrition-related apps is associated with health behavior
change. METHODS: A cross-sectional survey was administered to a total of 217
participants. Participants responded to questions on demographics, use of diet
and nutrition apps in the past 6 months, engagement and likability of apps, and
changes in the participant's dietary behaviors. Regression analysis was used to
identify factors associated with reported changes in theory and separately for
reported changes in actual behavior, after controlling for potential confounding
variables. RESULTS: The majority of study participants agreed or strongly agreed
with statements regarding app use increasing their motivation to eat a healthy
diet, improving their self-efficacy, and increasing their desire to set and
achieve health diet goals. Additionally, majority of participants strongly agreed
that using diet/nutrition apps led to changes in their behavior, namely increases
in actual goal setting to eat a healthy diet (58.5%, 127/217), increases in their
frequency of eating healthy foods (57.6%, 125/217), and increases in their
consistency of eating healthy foods (54.4%, 118/217). Participants also responded
favorably to questions related to engagement and likability of diet/nutrition
apps. A number of predictors were also positively associated with diet-related
behavior change. Theory (P<.001), app engagement (P<.001), app use (P<.003), and
education (P<.010) were all positively associated with behavior change.
CONCLUSIONS: Study findings indicate that the use of diet/nutrition apps is
associated with diet-related behavior change. Hence, diet- and nutrition-related
apps that focus on improving motivation, desire, self-efficacy, attitudes,
knowledge, and goal setting may be particularly useful. As the number of diet-
and nutrition-related apps continues to grow, developers should consider
integrating appropriate theoretical constructs for health behavior change into
the newly developed mobile apps.
PMID- 28694243
TI - Expanding our scientific horizons: utilization of unique model organisms in
biological research.
PMID- 28694242
TI - Chromatin stiffening underlies enhanced locus mobility after DNA damage in
budding yeast.
AB - DNA double-strand breaks (DSBs) induce a cellular response that involves histone
modifications and chromatin remodeling at the damaged site and increases
chromosome dynamics both locally at the damaged site and globally in the nucleus.
In parallel, it has become clear that the spatial organization and dynamics of
chromosomes can be largely explained by the statistical properties of tethered,
but randomly moving, polymer chains, characterized mainly by their rigidity and
compaction. How these properties of chromatin are affected during DNA damage
remains, however, unclear. Here, we use live cell microscopy to track chromatin
loci and measure distances between loci on yeast chromosome IV in thousands of
cells, in the presence or absence of genotoxic stress. We confirm that DSBs
result in enhanced chromatin subdiffusion and show that intrachromosomal
distances increase with DNA damage all along the chromosome. Our data can be
explained by an increase in chromatin rigidity, but not by chromatin
decondensation or centromeric untethering only. We provide evidence that
chromatin stiffening is mediated in part by histone H2A phosphorylation. Our
results support a genome-wide stiffening of the chromatin fiber as a consequence
of DNA damage and as a novel mechanism underlying increased chromatin mobility.
PMID- 28694244
TI - Tumor matrix stiffness promotes metastatic cancer cell interaction with the
endothelium.
AB - Tumor progression alters the composition and physical properties of the
extracellular matrix. Particularly, increased matrix stiffness has profound
effects on tumor growth and metastasis. While endothelial cells are key players
in cancer progression, the influence of tumor stiffness on the endothelium and
the impact on metastasis is unknown. Through quantitative mass spectrometry, we
find that the matricellular protein CCN1/CYR61 is highly regulated by stiffness
in endothelial cells. We show that stiffness-induced CCN1 activates beta-catenin
nuclear translocation and signaling and that this contributes to upregulate N
cadherin levels on the surface of the endothelium, in vitro This facilitates N
cadherin-dependent cancer cell-endothelium interaction. Using intravital imaging,
we show that knockout of Ccn1 in endothelial cells inhibits melanoma cancer cell
binding to the blood vessels, a critical step in cancer cell transit through the
vasculature to metastasize. Targeting stiffness-induced changes in the
vasculature, such as CCN1, is therefore a potential yet unappreciated mechanism
to impair metastasis.
PMID- 28694246
TI - MANAGEMENT OF ENDOCRINE DISEASE: Polycystic ovary syndrome and nonalcoholic fatty
liver disease.
AB - Polycystic ovary syndrome (PCOS) is a frequent endocrine disease in women, with a
number of metabolic and reproductive consequences. Obesity, insulin resistance
(IR) and type 2 diabetes are prominent metabolic characteristics of PCOS and
common factors affecting liver function and generating nonalcoholic fatty liver
disease (NAFLD). Multiple genes involved in the synthesis of androgens, cytokines
and IR, as well as acquired factors, such as endocrine disruptors, could
associate the etiopathogenesis of PCOS and NAFLD. Besides the high prevalence of
PCOS in general population, NAFLD was shown to be a frequent condition in
transition periods, such as adolescence and menopause. Although liver biopsy is
considered to be the gold standard for diagnosing liver damage, its routine use
in such a prevalent condition as PCOS can be related to a higher rate of
complications. Therefore, it is necessary to be able to diagnose NAFLD using
simple and reliable surrogate markers. Recently, fatty liver index and NAFLD
fatty liver score analyzed in large cohorts of PCOS women have been shown as
accurate markers of liver damage in this metabolically vulnerable population.
Lifestyle changes are still the mainstay of the management of NAFLD in PCOS,
although prospective randomized controlled clinical studies remain a priority in
the field. With regard to medications, metformin may be the drug of choice for
treating PCOS patients with NAFLD when pharmacologic therapy is considered.
Liraglutide use in obese PCOS has shown favorable effects on the predictors of
liver fibrosis. In this review, we aim to summarize the influence of the common
risk factors and to discuss the diagnostic approaches and management options for
NAFLD in patients with PCOS.
PMID- 28694245
TI - Fundamental cell cycle kinases collaborate to ensure timely destruction of the
synaptonemal complex during meiosis.
AB - The synaptonemal complex (SC) is a proteinaceous macromolecular assembly that
forms during meiotic prophase I and mediates adhesion of paired homologous
chromosomes along their entire lengths. Although prompt disassembly of the SC
during exit from prophase I is a landmark event of meiosis, the underlying
mechanism regulating SC destruction has remained elusive. Here, we show that DDK
(Dbf4-dependent Cdc7 kinase) is central to SC destruction. Upon exit from
prophase I, Dbf4, the regulatory subunit of DDK, directly associates with and is
phosphorylated by the Polo-like kinase Cdc5. In parallel, upregulated CDK1
activity also targets Dbf4. An enhanced Dbf4-Cdc5 interaction pronounced
phosphorylation of Dbf4 and accelerated SC destruction, while reduced/abolished
Dbf4 phosphorylation hampered destruction of SC proteins. SC destruction relieved
meiotic inhibition of the ubiquitous recombinase Rad51, suggesting that the
mitotic recombination machinery is reactivated following prophase I exit to
repair any persisting meiotic DNA double-strand breaks. Taken together, we
propose that the concerted action of DDK, Polo-like kinase, and CDK1 promotes
efficient SC destruction at the end of prophase I to ensure faithful inheritance
of the genome.
PMID- 28694247
TI - A case of unprovoked, precarious, patent foramen ovale protuberance.
AB - : This is a case of a precarious thrombotic mass straddling a patent foramen
ovale which had already embolised to the pulmonary circulation. The diagnosis was
initially deceptive and management challenging. LEARNING POINTS: Echocardiography
is mandated and can change management in haemodynamically unstable patients with
pulmonary emboli.Pulmonary embolism can be life-threatening.The authors propose
that urgent cardiac surgery is the safest treatment in the setting of highly
mobile, large volume, intra-cardiac thrombus.
PMID- 28694248
TI - Data from practices could enable earlier cancer diagnosis.
PMID- 28694249
TI - One in four women who had abortion in 2016 used hormonal or long acting
contraception, show figures.
PMID- 28694250
TI - Shortage of general practitioners in the NHS.
PMID- 28694251
TI - Advances in the causes and management of community acquired pneumonia in adults.
AB - Community acquired pneumonia remains a common cause of morbidity and mortality.
Usually, the causal organism is not identified and treatment remains empiric.
Recent computed tomography and magnetic resonance imaging studies have challenged
the accuracy of the clinical diagnosis of pneumonia, and epidemiologic studies
are changing our perspective of what causes community acquired pneumonia,
especially the role of viral pathogens and the frequent finding of multiple
pathogens. The past decade has seen increasing overuse of empiric coverage of
meticillin resistant Staphylococcus aureus and antibiotic resistant Gram negative
pathogens owing to inappropriate application of guidelines for healthcare
associated pneumonia. Optimal treatment remains a matter for debate, especially
in very sick patients, including the role of combination antibiotic therapy and
corticosteroids. Pneumonia care bundles are being defined to improve outcomes.
Increased recognition of both acute and long term cardiac complications is
shifting our concept of pneumonia from an acute lung disease to a multisystem
problem with adverse chronic health consequences.
PMID- 28694252
TI - Jean Holowach Thurston.
PMID- 28694253
TI - Implementing the compassion intervention, a model for integrated care for people
with advanced dementia towards the end of life in nursing homes: a naturalistic
feasibility study.
AB - BACKGROUND: Many people with dementia die in nursing homes, but quality of care
may be suboptimal. We developed the theory-driven 'Compassion Intervention' to
enhance end-of-life care in advanced dementia. OBJECTIVES: To (1) understand how
the Intervention operated in nursing homes in different health economies; (2)
collect preliminary outcome data and costs of an interdisciplinary care leader
(ICL) to facilitate the Intervention; (3) check the Intervention caused no harm.
DESIGN: A naturalistic feasibility study of Intervention implementation for 6
months. SETTINGS: Two nursing homes in northern London, UK. PARTICIPANTS: Thirty
residents with advanced dementia were assessed of whom nine were recruited for
data collection; four of these residents' family members were interviewed. Twenty
eight nursing home and external healthcare professionals participated in
interviews at 7 (n=19), 11 (n=19) and 15 months (n=10). INTERVENTION: An ICL led
two core Intervention components: (1) integrated, interdisciplinary assessment
and care; (2) education and support for paid and family carers. DATA COLLECTED:
Process and outcome data were collected. Symptoms were recorded monthly for
recruited residents. Semistructured interviews were conducted at 7, 11 and 15
months with nursing home staff and external healthcare professionals and at 7
months with family carers. ICL hours were costed using Department of Health and
Health Education England tariffs. RESULTS: Contextual differences were identified
between sites: nursing home 2 had lower involvement with external healthcare
services. Core components were implemented at both sites but multidisciplinary
meetings were only established in nursing home 1. The Intervention prompted
improvements in advance care planning, pain management and person-centred care;
we observed no harm. Six-month ICL costs were L18 255. CONCLUSIONS:
Implementation was feasible to differing degrees across sites, dependent on
context. Our data inform future testing to identify the Intervention's
effectiveness in improving end-of-life care in advanced dementia. TRIAL
REGISTRATION: ClinicalTrials.gov:NCT02840318: Results.
PMID- 28694254
TI - Why does the ovarian cancer screening fact box exist?
PMID- 28694255
TI - Soluble APP functions as a vascular niche signal that controls adult neural stem
cell number.
AB - The molecular mechanism by which NSC number is controlled in the neurogenic
regions of the adult brain is not fully understood but it has been shown that
vascular niche signals regulate neural stem cell (NSC) quiescence and growth.
Here, we have uncovered a role for soluble amyloid precursor protein (sAPP) as a
vascular niche signal in the subventricular zone (SVZ) of the lateral ventricle
of the adult mouse brain. sAPP suppresses NSC growth in culture. Further in vivo
studies on the role of APP in regulating NSC number in the SVZ clearly
demonstrate that endothelial deletion of App causes a significant increase in the
number of BrdU label-retaining NSCs in the SVZ, whereas NSC/astrocyte deletion of
App has no detectable effect on the NSC number. Taken together, these results
suggest that endothelial APP functions as a vascular niche signal that negatively
regulates NSC growth to control the NSC number in the SVZ.
PMID- 28694256
TI - Multiple modes of Lrp4 function in modulation of Wnt/beta-catenin signaling
during tooth development.
AB - During development and homeostasis, precise control of Wnt/beta-catenin signaling
is in part achieved by secreted and membrane proteins that negatively control
activity of the Wnt co-receptors Lrp5 and Lrp6. Lrp4 is related to Lrp5/6 and is
implicated in modulation of Wnt/beta-catenin signaling, presumably through its
ability to bind to the Wise (Sostdc1)/sclerostin (Sost) family of Wnt
antagonists. To gain insights into the molecular mechanisms of Lrp4 function in
modulating Wnt signaling, we performed an array of genetic analyses in murine
tooth development, where Lrp4 and Wise play important roles. We provide genetic
evidence that Lrp4 mediates the Wnt inhibitory function of Wise and also
modulates Wnt/beta-catenin signaling independently of Wise. Chimeric receptor
analyses raise the possibility that the Lrp4 extracellular domain interacts with
Wnt ligands, as well as the Wnt antagonists. Diverse modes of Lrp4 function are
supported by severe tooth phenotypes of mice carrying a human mutation known to
abolish Lrp4 binding to Sost. Our data suggest a model whereby Lrp4 modulates
Wnt/beta-catenin signaling via interaction with Wnt ligands and antagonists in a
context-dependent manner.
PMID- 28694257
TI - BMP signaling regulates satellite cell-dependent postnatal muscle growth.
AB - Postnatal growth of skeletal muscle largely depends on the expansion and
differentiation of resident stem cells, the so-called satellite cells. Here, we
demonstrate that postnatal satellite cells express components of the bone
morphogenetic protein (BMP) signaling machinery. Overexpression of noggin in
postnatal mice (to antagonize BMP ligands), satellite cell-specific knockout of
Alk3 (the gene encoding the BMP transmembrane receptor) or overexpression of
inhibitory SMAD6 decreased satellite cell proliferation and accretion during
myofiber growth, and ultimately retarded muscle growth. Moreover, reduced BMP
signaling diminished the adult satellite cell pool. Abrogation of BMP signaling
in satellite cell-derived primary myoblasts strongly diminished cell
proliferation and upregulated the expression of cell cycle inhibitors p21 and p57
In conclusion, these results show that BMP signaling defines postnatal muscle
development by regulating satellite cell-dependent myofiber growth and the
generation of the adult muscle stem cell pool.
PMID- 28694258
TI - PLCzeta is the physiological trigger of the Ca2+ oscillations that induce
embryogenesis in mammals but conception can occur in its absence.
AB - Activation of the egg by the sperm is the first, vital stage of embryogenesis.
The sperm protein PLCzeta has been proposed as the physiological agent that
triggers the Ca2+ oscillations that normally initiate embryogenesis. Consistent
with this, recombinant PLCzeta induces Ca2+ oscillations in eggs and debilitating
mutations in the PLCZ1 gene are associated with infertility in men. However,
there has been no evidence that knockout of the gene encoding PLCzeta abolishes
the ability of sperm to induce Ca2+ oscillations in eggs. Here, we show that
sperm derived from Plcz1-/- male mice fail to trigger Ca2+ oscillations in eggs,
cause polyspermy and thus demonstrate that PLCzeta is the physiological trigger
of these Ca2+ oscillations. Remarkably, some eggs fertilized by PLCzeta-null
sperm can develop, albeit at greatly reduced efficiency, and after a significant
time-delay. In addition, Plcz1-/- males are subfertile but not sterile,
suggesting that in the absence of PLCzeta, spontaneous egg activation can
eventually occur via an alternative route. This is the first demonstration that
in vivo fertilization without the normal physiological trigger of egg activation
can result in offspring. PLCzeta-null sperm now make it possible to resolve long
standing questions in fertilization biology, and to test the efficacy and safety
of procedures used to treat human infertility.
PMID- 28694259
TI - High-efficiency non-mosaic CRISPR-mediated knock-in and indel mutation in F0
Xenopus.
AB - The revolution in CRISPR-mediated genome editing has enabled the mutation and
insertion of virtually any DNA sequence, particularly in cell culture where
selection can be used to recover relatively rare homologous recombination events.
The efficient use of this technology in animal models still presents a number of
challenges, including the time to establish mutant lines, mosaic gene editing in
founder animals, and low homologous recombination rates. Here we report a method
for CRISPR-mediated genome editing in Xenopus oocytes with homology-directed
repair (HDR) that provides efficient non-mosaic targeted insertion of small DNA
fragments (40-50 nucleotides) in 4.4-25.7% of F0 tadpoles, with germline
transmission. For both CRISPR/Cas9-mediated HDR gene editing and indel mutation,
the gene-edited F0 embryos are uniformly heterozygous, consistent with a mutation
in only the maternal genome. In addition to efficient tagging of proteins in
vivo, this HDR methodology will allow researchers to create patient-specific
mutations for human disease modeling in Xenopus.
PMID- 28694260
TI - Coup-TF1 and Coup-TF2 control subtype and laminar identity of MGE-derived
neocortical interneurons.
AB - Distinct cortical interneuron (CIN) subtypes have unique circuit functions;
dysfunction in specific subtypes is implicated in neuropsychiatric disorders.
Somatostatin- and parvalbumin-expressing (SST+ and PV+) interneurons are the two
major subtypes generated by medial ganglionic eminence (MGE) progenitors. Spatial
and temporal mechanisms governing their cell-fate specification and differential
integration into cortical layers are largely unknown. We provide evidence that
Coup-TF1 and Coup-TF2 (Nr2f1 and Nr2f2) transcription factor expression in an arc
shaped progenitor domain within the MGE promotes time-dependent survival of this
neuroepithelium and the time-dependent specification of layer V SST+ CINs. Coup
TF1 and Coup-TF2 autonomously repress PV+ fate in MGE progenitors, in part
through directly driving Sox6 expression. These results have identified, in
mouse, a transcriptional pathway that controls SST-PV fate.
PMID- 28694262
TI - Bending the Trends.
PMID- 28694263
TI - Now is the Time to Address Substance Use Disorders in Primary Care.
PMID- 28694264
TI - Medication-Assisted Treatment Should Be Part of Every Family Physician's
Practice: Yes.
PMID- 28694265
TI - Medication-Assisted Treatment Should Be Part of Every Family Physician's
Practice: No.
PMID- 28694266
TI - Comparing Medical Ecology, Utilization, and Expenditures Between 1996-1997 and
2011-2012.
AB - PURPOSE: This study compared ecology (number of individuals using a service),
utilization (number of services used), and expenditures (dollars spent) for
various categories of medical services between primarily 1996-1997 and 2011-2012.
METHODS: A repeated cross-sectional study was performed using nationally
representative data mainly from the 1996, 1997, 2011, and 2012 Medical
Expenditure Panel Survey (MEPS). These data were augmented with the 2002-2003
MEPS as well as the 1999-2000 and 2011-2012 National Heath and Nutrition
Examination Survey. Individuals (number per 1,000 people), utilization, and
expenditures during an average month in 1996-1997 and 2011-2012 were determined
for 15 categories of services. RESULTS: The number of individuals who used
various medical services was unchanged for many categories of services (total,
outpatient, outpatient physician, users of prescribed medications, primary care
and specialty physicians, inpatient hospitalization, and emergency department).
It was, however, increased for others (optometry/podiatry, therapy, and
alternative/complementary medicine) and decreased for a few (dental and home
health). The number of services used (utilization) largely mirrored the findings
for individual use, with the exception of an increase in the number of prescribed
medications and a decrease in number of primary care physician visits. There were
large increases in dollars spent (expenditures) in every category with the
exception of primary care physician and home health; the largest absolute
increases were in prescribed medications, specialty physicians, emergency
department visits, and likely inpatient hospitalizations. CONCLUSIONS: Although
the number of individuals with visits during an average month and the total
utilization of medical services were largely unchanged between the 2 time
periods, total expenditures increased markedly. The increases in expenditure
varied dramatically by category.
PMID- 28694267
TI - Mobility of US Rural Primary Care Physicians During 2000-2014.
AB - PURPOSE: Despite considerable investment in increasing the number of primary care
physicians in rural shortage areas, little is known about their movement rates
and factors influencing their mobility. We aimed to characterize geographic
mobility among rural primary care physicians, and to identify location and
individual factors that influence such mobility. METHODS: Using data from the
American Medical Association Physician Masterfile for each clinically active US
physician, we created seven 2-year (biennial) mobility periods during 2000-2014.
These periods were merged with county-level "rurality," physician supply,
economic characteristics, key demographic measures, and individual physician
characteristics. We computed (1) mobility rates of physicians by rurality; (2)
linear regression models of county-level rural nonretention (departure); and (3)
logit models of physicians leaving rural practice. RESULTS: Biennial turnover was
about 17% among physicians aged 45 and younger, compared with 9% among physicians
aged 46 to 65, with little difference between rural and metropolitan groups.
County-level physician mobility was higher for counties that lacked a hospital
(absolute increase = 5.7%), had a smaller population size, and had lower primary
care physician supply, but area-level economic and demographic factors had little
impact. Female physicians (odds ratios = 1.24 and 1.46 for those aged 45 or
younger and those aged 46 to 65, respectively) and physicians born in a
metropolitan area (odds ratios = 1.75 and 1.56 for those aged 45 or younger and
those aged 46 to 65, respectively) were more likely to leave rural practice.
CONCLUSIONS: These flndings provide national-level evidence of rural physician
mobility rates and factors associated with both county-level retention and
individual-level departures. Outcomes were notably poorer in the most remote
locations and those already having poorer physician supply and professional
support. Rural health workforce planners and policymakers must be cognizant of
these key factors to more effectively target retention policies and to take into
account the additional support needed by these more vulnerable communities.
PMID- 28694268
TI - The Effect of Changes in Cervical Cancer Screening Guidelines on Chlamydia
Testing.
AB - PURPOSE: Many chlamydia infections are identified through screening, which is
frequently offered to females concomitantly with cervical cancer screening.
Recent cervical cancer screening guidelines recommend screening less frequently
and starting later. We sought to evaluate the impact of the May 2012 Ontario,
Canada, cervical cancer screening guideline change on Papanicolaou (Pap) and
chlamydia trachomatis (chlamydia) testing and incidence. METHODS: We extracted
population-based physician billing claims data to identify Pap and chlamydia
tests and public health surveillance data to identify chlamydia cases. We used
interrupted time series analysis of quarterly data spanning 2 years before and
after the guideline change and fitted segmented linear regression or rational
functions to the outcomes using autoregressive integrated moving average models.
Outcomes were stratified by sex and age group. RESULTS: Two years after the
guideline change, we observed reduced chlamydia testing in females, with the
greatest relative reduction (25.5%) among those aged 15 to 19 years. We also
observed decreases in reported chlamydia incidence for females aged 15 to 19
years and 20 to 24 years (relative reductions of 16.8% and 14.4%, respectively).
Chlamydia incidence remained the same for males, despite increased chlamydia
testing. CONCLUSIONS: Recent cervical cancer screening guideline changes in
Ontario were associated with reduced chlamydia testing and reported new cases of
chlamydia in females. Females aged 15 to 19 years, who are at high risk for
chlamydia if sexually active, and who no longer warrant cervical cancer
screening, were disproportionately affected. Females should be tested for
chlamydia based on risk, regardless of need for Pap testing.
PMID- 28694269
TI - Delivery of Brief Interventions for Heavy Drinking in Primary Care: Outcomes of
the ODHIN 5-Country Cluster Randomized Trial.
AB - PURPOSE: We aimed to test whether 3 strategies-training and support, financial
reimbursement, and an option to direct screen-positive patients to an Internet
based method of giving brief advice-have a longer-term effect on primary care
clinicians' delivery of screening and advice to heavy drinkers operationalized
with the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) tool.
METHODS: We undertook a cluster randomized factorial trial with a 12-week
implementation period in 120 primary health care units throughout Catalonia,
England, Netherlands, Poland, and Sweden. Units were randomized to 8 groups: care
as usual (control); training and support alone; financial reimbursement alone;
electronic brief advice alone; paired combinations of these conditions; and all 3
combined. The primary outcome was the proportion of consulting adult patients
(aged 18 years and older) receiving intervention-screening and, if screen
positive, advice-at 9 months. RESULTS: Based on the factorial design, the ratio
of the log of the proportion of patients given intervention at the 9-month follow
up was 1.39 (95% CI, 1.03-1.88) in units that received training and support as
compared with units that did not. Neither financial reimbursement nor directing
screen-positive patients to electronic brief advice led to a higher proportion of
patients receiving intervention. CONCLUSIONS: Training and support of primary
health care units has a lasting, albeit small, impact on the proportion of adult
patients given an alcohol intervention at 9 months.
PMID- 28694270
TI - Swimming Against the Tide: Primary Care Physicians' Views on Deprescribing in
Everyday Practice.
AB - PURPOSE: Avoidable hospitalizations due to adverse drug events and high-risk
prescribing are common in older people. Primary care physicians prescribe most on
going medicines. Deprescribing has long been essential to best prescribing
practice. We sought to explore the views of primary care physicians on the
barriers and facilitators to deprescribing in everyday practice to inform the
development of an intervention to support safer prescribing. METHODS: We used a
snowball sampling technique to identify potential participants. Physicians were
selected on the basis of years in practice, employment status, and practice
setting, with an additional focus on information-rich participants. Twenty-four
semistructured interviews were audio-recorded, transcribed verbatim, and analyzed
to identify emergent themes. RESULTS: Physicians described deprescribing as
"swimming against the tide" of patient expectations, the medical culture of
prescribing, and organizational constraints. They said deprescribing came with
inherent risks for both themselves and patients and conveyed a sense of
vulnerability in practice. The only incentive to deprescribing they identified
was the duty to do what was right for the patient. Physicians recommended
organizational changes to support safer prescribing, including targeted funding
for annual medicines review, computer prompts, improved information flows between
prescribers, improved access to expert advice and user-friendly decision support,
increased availability of non-pharmaceutical therapies, and enhanced patient
engagement in medicines management. CONCLUSIONS: Interventions to support safer
prescribing in everyday practice should consider the sociocultural, personal,
relational, and organizational constraints on deprescribing. Regulations and
policies should be designed to support physicians in practicing according to
their professional ethical values.
PMID- 28694271
TI - Proposed Clinical Decision Rules to Diagnose Acute Rhinosinusitis Among Adults in
Primary Care.
AB - PURPOSE: To reduce inappropriate antibiotic prescribing, we sought to develop a
clinical decision rule for the diagnosis of acute rhinosinusitis and acute
bacterial rhinosinusitis. METHODS: Multivariate analysis and classification and
regression tree (CART) analysis were used to develop clinical decision rules for
the diagnosis of acute rhinosinusitis, defined using 3 different reference
standards (purulent antral puncture fluid or abnormal finding on a computed
tomographic (CT) scan; for acute bacterial rhinosinusitis, we used a positive
bacterial culture of antral fluid). Signs, symptoms, C-reactive protein (CRP),
and reference standard tests were prospectively recorded in 175 Danish patients
aged 18 to 65 years seeking care for suspected acute rhinosinusitis. For each
reference standard, we developed 2 clinical decision rules: a point score based
on a logistic regression model and an algorithm based on a CART model. We
identified low-, moderate-, and high-risk groups for acute rhinosinusitis or
acute bacterial rhinosinusitis for each clinical decision rule. RESULTS: The
point scores each had between 5 and 6 predictors, and an area under the receiver
operating characteristic curve (AUROCC) between 0.721 and 0.767. For positive
bacterial culture as the reference standard, low-, moderate-, and high-risk
groups had a 16%, 49%, and 73% likelihood of acute bacterial rhinosinusitis,
respectively. CART models had an AUROCC ranging from 0.783 to 0.827. For positive
bacterial culture as the reference standard, low-, moderate-, and high-risk
groups had a likelihood of acute bacterial rhinosinusitis of 6%, 31%, and 59%
respectively. CONCLUSIONS: We have developed a series of clinical decision rules
integrating signs, symptoms, and CRP to diagnose acute rhinosinusitis and acute
bacterial rhinosinusitis with good accuracy. They now require prospective
validation and an assessment of their effect on clinical and process outcomes.
PMID- 28694272
TI - Mortality Associated With Time in and Out of Buprenorphine Treatment in French
Office-Based General Practice: A 7-Year Cohort Study.
AB - In France, most cases of opioid use disorder are treated with buprenorphine by
general practitioners in private practice. Using reimbursement data of a
representative sample of the French population, Echantillon Generaliste des
Beneficiaires, we investigated mortality during periods when patients were in and
out of treatment in a cohort of 713 new users of buprenorphine having a mean (SD)
follow-up of 4.5 (1.5) years. The mortality rate was 0.63 per 100 person-years
(95% CI, 0.40-0.85) overall. In a multivariate Cox regression model, compared
with being in treatment, being out of treatment was associated with a markedly
increased risk of death (hazard ratio = 29.04; 95% CI, 10.04-83.99).
Buprenorphine appears to be a strong protective factor against mortality.
PMID- 28694273
TI - Barriers Rural Physicians Face Prescribing Buprenorphine for Opioid Use Disorder.
AB - Opioid use disorder is a serious public health problem. Management with
buprenorphine is an effective, office-based, medication-assisted treatment, but
60.1% of rural counties in the United States lack a physician with a Drug
Enforcement Agency waiver to prescribe buprenorphine. This national study
surveyed all rural physicians who have received a waiver in the United States and
found that those who were not actively prescribing buprenorphine reported
significantly more barriers than those who were, regardless of whether they were
treating the maximum number of patients their waiver allowed. These findings
suggest the need for tailored strategies to address barriers to providing
buprenorphine for opioid use disorder and to support physicians who are adding or
maintaining this service.
PMID- 28694274
TI - Challenges for Insured Patients in Accessing Behavioral Health Care.
AB - The Patient Protection and Affordable Care Act (ACA) mandates that health
insurance plans include sufficient access to behavioral health providers, but
lacks specific guidelines to define sufficient access Using a secret shopper
methodology, we called behavioral health providers in the Denver metropolitan
area networked with 3 large insurance companies. We found that, depending on
insurance company and level of training, 9.8% to 59% of providers could offer a
new patient appointment, with psychiatry appointments being particularly
difficult to schedule. These findings are consistent with similar studies
conducted in other regions, suggesting that access to outpatient behavioral
health care is limited despite existing ACA regulations.
PMID- 28694275
TI - The Chief Primary Care Medical Officer: Restoring Continuity.
AB - The year 2016 marked the 20th anniversary of the hospitalist profession, with
more than 50,000 physicians identifying as hospitalists. The Achilles heel of
hospitalist medicine, however, is discontinuity. Despite many current payment and
delivery systems rewarding this discontinuity and severing long-term
relationships between patient and primary care teams at the hospital door,
primary care does not stop being important when a person is admitted to the
hospital. The notion of a broken primary care continuum is not an academic
construct, it causes real harm to patients. As a step toward fixing the
discontinuity in our health care systems, we propose that every hospital needs a
Chief Primary Care Medical Officer (CPCMO), an expert in practice across the
spectrum of care. The CPCMO can lead hospital efforts to create systems that
ensure primary care's continuum is complete, while strengthening physician
collaboration across specialties, and moving toward achieving the Quadruple Aim
of enhancing patient experience, improving population health, reducing costs, and
improving the work life of health care providers. For hospitals operating on
value-based payment structures, anticipated improvement in measurable outcomes
such as decreased length of stay, decreased readmission rates, improved
transitions of care, improved patient satisfaction, improved access to primary
care, and improved patient health, will enhance the rate of return on the
hospital's investment. The speciality of family medicine should reevaluate our
purpose, and reembrace our mission as personal physicians by championing the
creation of Chief Primary Care Medical Officers.
PMID- 28694276
TI - Denial: The Greatest Barrier to the Opioid Epidemic.
AB - "Why can't you be like my old doctor?" This essay explores my experiences as a
new family physician in a rural town endemic with liberal opioid prescribing
practices and opioid addiction. I detail my inner turmoil while overcoming
resistance to change, the influence of these experiences on my professional
growth, and my decision to offer medication-assisted treatment.
PMID- 28694277
TI - Disenfranchised Grief and Physician Burnout.
AB - Over the span of their career, physicians experience changes to their
professional role and professional identity. The process of continual adaptation
in their work setting incurs losses. These losses can be ambiguous, cumulative,
and may require grieving. Grief in the workplace is unsanctioned, and may
contribute to physicians' experience of burnout (emotional exhaustion,
depersonalization, low sense of achievement). Acknowledging loss, validating
grief, and being prescient in dealing with physician burnout is essential.
PMID- 28694278
TI - Cultivating the Inner Life of a Physician Through Written Reflection.
AB - All of us have an "inner life" that forms the core of who we are. It shapes and
is shaped by our actions and experiences. During physician training, attention to
residents' inner life requires a focus on their beliefs and emotions as well as
their ethical and spiritual development, topics often considered to be outside
the realm of clinical training and practice. We suggest that written reflections,
as part of medical residency curriculum, can allow residents to explore their
inner lives. The depth and range of residents' explorations show the value of
adding brief, protected time for residents to explore their hopes, joys,
struggles, and feelings, and to develop meaning from their experiences with
patients.
PMID- 28694279
TI - Using Patient-Entered Data to Supercharge Self-Management.
PMID- 28694280
TI - Expanding Primary Care Access: A Telehealth Success Story.
PMID- 28694288
TI - Chief clinical information officers: clinical leadership for a digital age.
PMID- 28694289
TI - Graham Ayliffe.
PMID- 28694290
TI - Current Scope of Practice for Newborn Care in Non-Intensive Hospital Settings.
PMID- 28694292
TI - Specialized Proresolving Mediators Rescue Infant Mice from Lethal Citrobacter
rodentium Infection and Promote Immunity against Reinfection.
AB - Infants are generally highly susceptible to oral pathogens. Intestinal infection
and the associated diarrhea are significant global causes of morbidity and
mortality in infants. Among the enteric pathogens, enteropathogenic Escherichia
coli (EPEC) stands out as showing the highest risk for infection-induced death in
infants <=12 months old. We have developed an experimental model of infant
infection with EPEC, using the mouse-specific pathogen Citrobacter rodentium Our
murine infant model is similar to EPEC infection in human infants since infant
mice are much more susceptible to C. rodentium infection than adult mice; infants
infected with 50-fold fewer bacteria than the standard adult dose uniformly
succumbed to the infection. Infant infection is characterized by high early and
sustained bacterial titers and profound intestinal inflammation associated with
extensive necrosis and systemic dissemination of the bacteria. Therefore, it
seems likely that infant deaths result from sepsis secondary to intestinal
damage. Recently, specialized proresolving mediators (SPM) have been found to
exert profound beneficial effects in adult models of infection. Thus, we
investigated the actions of two proresolving lipid mediators, resolvin D1 (RvD1)
and resolvin D5 (RvD5), on the course of infection in infants. Strikingly,
postinfection treatment with RvD1 and RvD5 reduced bacterial loads, mitigated
inflammation, and rescued the infants from death. Furthermore, postinfection
treatment with RvD1 and RvD5 led to protection from reinfection associated with
C. rodentium-specific IgG responses comparable to those in adults. These results
indicate that SPM may provide novel therapeutic tools for the treatment of
pathological intestinal infections in infants.
PMID- 28694291
TI - Differential Regulation of Mas-Related G Protein-Coupled Receptor X2-Mediated
Mast Cell Degranulation by Antimicrobial Host Defense Peptides and Porphyromonas
gingivalis Lipopolysaccharide.
AB - Porphyromonas gingivalis is a keystone pathogen that contributes to periodontal
pathogenesis by disrupting host-microbe homeostasis and promoting dysbiosis. The
virulence of P. gingivalis likely reflects an alteration in the lipid A
composition of its lipopolysaccharide (LPS) from the penta-acylated (PgLPS1690)
to the tetra-acylated (PgLPS1435/1449) form. Mast cells play an important role in
periodontitis, but the mechanisms of their activation and regulation remain
unknown. The expression of epithelium- and neutrophil-derived host defense
peptides (HDPs) (LL-37 and human beta-defensin-3), which activate mast cells via
Mas-related G protein-coupled receptor X2 (MRGPRX2), is increased in
periodontitis. We found that MRGPRX2-expressing mast cells are present in normal
gingiva and that their numbers are elevated in patients with chronic
periodontitis. Furthermore, HDPs stimulated degranulation in a human mast cell
line (LAD2) and in RBL-2H3 cells stably expressing MRGPRX2 (RBL-MRGPRX2).
PgLPS1690 caused substantial inhibition of HDP-induced mast cell degranulation,
but PgLPS1435/1449 had no effect. A fluorescently labeled HDP (FAM-LL-37) bound
to RBL-MRGPRX2 cells, and PgLPS1690 inhibited this binding, but PgLPS1435/1449
had no effect. These findings suggest that low-level inflammation induced by
HDP/MRGPRX2-mediated mast cell degranulation contributes to gingival homeostasis
but that sustained inflammation due to elevated levels of both HDPs and MRGPRX2
expressing mast cells promotes periodontal disease. Furthermore, differential
regulation of HDP-induced mast cell degranulation by PgLPS1690 and PgLPS1435/1449
may contribute to the modulation of disease progression.
PMID- 28694293
TI - The Trophic Life Cycle Stage of the Opportunistic Fungal Pathogen Pneumocystis
murina Hinders the Ability of Dendritic Cells To Stimulate CD4+ T Cell Responses.
AB - The life cycle of the opportunistic fungal pathogen Pneumocystis murina consists
of a trophic stage and an ascus-like cystic stage. Infection with the cyst stage
induces proinflammatory immune responses, while trophic forms suppress the
cytokine response to multiple pathogen-associated molecular patterns (PAMPs),
including beta-glucan. A targeted gene expression assay was used to evaluate the
dendritic cell response following stimulation with trophic forms alone, with a
normal mixture of trophic forms and cysts, or with beta-glucan. We demonstrate
that stimulation with trophic forms downregulated the expression of multiple
genes normally associated with the response to infection, including genes
encoding transcription factors. Trophic forms also suppressed the expression of
genes related to antigen processing and presentation, including the gene encoding
the major histocompatibility complex (MHC) class II transactivator, CIITA.
Stimulation of dendritic cells with trophic forms, but not a mixture of trophic
forms and cysts, reduced the expression of MHC class II and the costimulatory
molecule CD40 on the surface of the cells. These defects in the expression of MHC
class II and costimulatory molecules corresponded with a reduced capacity for
trophic form-loaded dendritic cells to stimulate CD4+ T cell proliferation and
polarization. These data are consistent with the delayed innate and adaptive
responses previously observed in immunocompetent mice inoculated with trophic
forms compared to responses in mice inoculated with a mixture of trophic forms
and cysts. We propose that trophic forms broadly inhibit the ability of dendritic
cells to fulfill their role as antigen-presenting cells.
PMID- 28694294
TI - Bacteroides fragilis Enterotoxin Induces Formation of Autophagosomes in
Endothelial Cells but Interferes with Fusion with Lysosomes for Complete
Autophagic Flux through a Mitogen-Activated Protein Kinase-, AP-1-, and C/EBP
Homologous Protein-Dependent Pathway.
AB - Bacteroides fragilis enterotoxin (BFT), a virulence factor of enterotoxigenic B.
fragilis (ETBF), plays an essential role in mucosal inflammation. Although
autophagy contributes to the pathogenesis of diverse infectious diseases, little
is known about autophagy in ETBF infection. This study was conducted to
investigate the role of BFT in the autophagic process in endothelial cells (ECs).
Stimulation of human umbilical vein ECs (HUVECs) with BFT increased light chain 3
protein II (LC3-II) conversion from LC3-I and protein expression of p62, Atg5,
and Atg12. In addition, BFT-exposed ECs showed increased indices of
autophagosomal fusion with lysosomes such as LC3-lysosome-associated protein 2
(LAMP2) colocalization and the percentage of red vesicles monitored by the
expression of dual-tagged LC3B. BFT also upregulated expression of C/EBP
homologous protein (CHOP), and inhibition of CHOP significantly increased indices
of autophagosomal fusion with lysosomes. BFT activated an AP-1 transcription
factor, in which suppression of AP-1 activity significantly downregulated CHOP
and augmented autophagosomal fusion with lysosomes. Furthermore, suppression of
Jun N-terminal protein kinase (JNK) mitogen-activated protein kinase (MAPK)
significantly inhibited the AP-1 and CHOP signals, leading to an increase in
autophagosomal fusion with lysosomes in BFT-stimulated ECs. These results suggest
that BFT induced accumulation of autophagosomes in ECs, but activation of a
signaling pathway involving JNK, AP-1, and CHOP may interfere with complete
autophagy.
PMID- 28694295
TI - In Vivo Analysis of the Viable Microbiota and Helicobacter pylori Transcriptome
in Gastric Infection and Early Stages of Carcinogenesis.
AB - Emerging evidence shows that the human microbiota plays a larger role in disease
progression and health than previously anticipated. Helicobacter pylori, the
causative agent of gastric cancer and duodenal and gastric ulcers, was early
associated with gastric disease, but it has also been proposed that the
accompanying microbiota in Helicobacter pylori-infected individuals might affect
disease progression and gastric cancer development. In this study, the
composition of the transcriptionally active microbial community and H. pylori
gene expression were determined using metatranscriptomic RNA sequencing of
stomach biopsy specimens from individuals with different H. pylori infection
statuses and premalignant tissue changes. The results show that H. pylori
completely dominates the microbiota not only in infected individuals but also in
most individuals classified as H. pylori uninfected using conventional methods.
Furthermore, H. pylori abundance is positively correlated with the presence of
Campylobacter, Deinococcus, and Sulfurospirillum Finally, we quantified the
expression of a large number of Helicobacter pylori genes and found high
expression of genes involved in pH regulation and nickel transport. Our study is
the first to dissect the viable microbiota of the human stomach by
metatranscriptomic analysis, and it shows that metatranscriptomic analysis of the
gastric microbiota is feasible and can provide new insights into how bacteria
respond in vivo to variations in the stomach microenvironment and at different
stages of disease progression.
PMID- 28694296
TI - Apolipoprotein C-III inhibits triglyceride hydrolysis by GPIHBP1-bound LPL.
AB - apoC-III is often assumed to retard the intravascular processing of triglyceride
rich lipoproteins (TRLs) by inhibiting LPL, but that view is based largely on
studies of free LPL. We now recognize that intravascular LPL is neither free nor
loosely bound, but instead is tightly bound to glycosylphosphatidylinositol
anchored HDL-binding protein 1 (GPIHBP1) on endothelial cells. Here, we revisited
the effects of apoC-III on LPL, focusing on apoC-III's capacity to affect the
activity of GPIHBP1-bound LPL. We found that TRLs from APOC3 transgenic mice
bound normally to GPIHBP1-bound LPL on cultured cells in vitro and to heart
capillaries in vivo. However, the triglycerides in apoC-III-enriched TRLs were
hydrolyzed more slowly by free LPL, and the inhibitory effect of apoC-III on
triglyceride lipolysis was exaggerated when LPL was bound to GPIHBP1 on the
surface of agarose beads. Also, recombinant apoC-III reduced triglyceride
hydrolysis by free LPL only modestly, but the inhibitory effect was greater when
the LPL was bound to GPIHBP1. A mutant apoC-III associated with low plasma
triglyceride levels (p.A23T) displayed a reduced capacity to inhibit free and
GPIHBP1-bound LPL. Our results show that apoC-III potently inhibits triglyceride
hydrolysis when LPL is bound to GPIHBP1.
PMID- 28694297
TI - Sensitive and selective quantification of free and total malondialdehyde in
plasma using UHPLC-HRMS.
AB - Quantification of malondialdehyde (MDA) as a marker of lipid peroxidation is
relevant for many research fields. We describe a new sensitive and selective
method to measure free and total plasmatic MDA using derivatization with 2,4
dinitrophenylhydrazine (DNPH) and ultra-HPLC-high-resolution MS. Free and total
MDA were extracted from minute sample amounts (10 MUl) using acidic precipitation
and alkaline hydrolysis followed by acidic precipitation, respectively.
Derivatization was completed within 10 min at room temperature, and the excess
DNPH discarded by liquid-liquid extraction. Quantification was achieved by
internal standardization using dideuterated MDA as internal standard. The
method's lowest limit of quantification was 100 nM and linearity spanned greater
than three orders of magnitude. Intra- and inter-day precisions for total MDA
were 2.9% and 3.0%, respectively, and those for free MDA were 12.8% and 24.9%,
respectively. Accuracy was 101% and 107% at low and high concentrations,
respectively. In human plasma, free MDA levels were 120 nM (SD 36.26) and total
MDA levels were 6.7 MUM (SD 0.46). In addition, we show the applicability of this
method to measure MDA plasma levels from a variety of animal species, making it
invaluable to scientists in various fields.
PMID- 28694299
TI - Scrapped training programme was helping to increase GP numbers, review finds.
PMID- 28694298
TI - Compound-specific isotope analysis resolves the dietary origin of docosahexaenoic
acid in the mouse brain.
AB - DHA (22:6n-3) may be derived from two dietary sources, preformed dietary DHA or
through synthesis from alpha-linolenic acid (ALA; 18:3n-3). However, conventional
methods cannot distinguish between DHA derived from either source without the use
of costly labeled tracers. In the present study, we demonstrate the proof-of
concept that compound-specific isotope analysis (CSIA) by GC-isotope ratio mass
spectrometry (IRMS) can differentiate between sources of brain DHA based on
differences in natural 13C enrichment. Mice were fed diets containing either
purified ALA or DHA as the sole n-3 PUFA. Extracted lipids were analyzed by CSIA
for natural abundance 13C enrichment. Brain DHA from DHA-fed mice was
significantly more enriched (-23.320/00 to -21.920/00) compared with mice on the
ALA diet (-28.250/00 to -27.490/00). The measured 13C enrichment of brain DHA
closely resembled the dietary n-3 PUFA source, -21.860/00 and -28.220/00 for DHA
and ALA, respectively. The dietary effect on DHA 13C enrichment was similar in
liver and blood fractions. Our results demonstrate the effectiveness of CSIA, at
natural 13C enrichment, to differentiate between the incorporation of preformed
or synthesized DHA into the brain and other tissues without the need for tracers.
PMID- 28694300
TI - The regulation of oxytocin and oxytocin receptor in human placenta according to
gestational age.
AB - Oxytocin (OXT) is a peptide hormone that plays a central role in the regulation
of parturition and lactation. OXT signaling is mediated by OXT receptor (OXTR),
which shows species- and tissue-specific expressions and gene regulation. In the
present study, we examined the synthesis of OXT and OXTR in human placenta tissue
according to gestational age. A total of 48 placentas were divided into early
preterm, late preterm and term groups depending on gestational age, and
expression of OXT and OXTR was evaluated. First, OXT and OXTR mRNA and protein
were detected in normal placenta tissue via Q-PCR, Dot-blot and Western blot
assay. Both OXT and OXTR levels in normal placenta increased gradually in the
late stage of pregnancy, suggesting that local OXT may play a critical role in
the function of the placenta. To determine the regulatory mechanism of OXT,
placental BeWo cells were administrated estrogen (E2) or progesterone (P4), and
expression of OXT and OXTR was tested. The mRNA and protein levels of OXT and
OXTR were upregulated by E2 but blocked by co-treatment with P4 In order to
confirm the estrogen receptor (ESR)-mediated signaling, we administrated ESR
antagonists together with E2 to BeWo cells. As a result, both OXT and OXTR were
significantly altered by ESR1 antagonist (MPP) while moderately regulated by ESR2
antagonist (PHTPP). These results suggest that OXT and OXTR are controlled mainly
by E2 in the placenta via ESR1 and thus may play physiological functions in the
human placenta during the late stage of pregnancy.
PMID- 28694301
TI - Helminth antigens counteract a rapid high-fat diet-induced decrease in adipose
tissue eosinophils.
AB - Brown adipose tissue (BAT) activation and white adipose tissue (WAT) beiging can
increase energy expenditure and have the potential to reduce obesity and
associated diseases. The immune system is a potential target in mediating brown
and beige adipocyte activation. Type 2 and anti-inflammatory immune cells
contribute to metabolic homeostasis within lean WAT, with a prominent role for
eosinophils and interleukin (IL)-4-induced anti-inflammatory macrophages. We
determined eosinophil numbers in epididymal WAT (EpAT), subcutaneous WAT (ScAT)
and BAT after 1 day, 3 days or 1 week of high-fat diet (HFD) feeding in C57Bl/6
mice. One day of HFD resulted in a rapid drop in eosinophil numbers in EpAT and
BAT, and after 3 days, in ScAT. In an attempt to restore this HFD-induced drop in
adipose tissue eosinophils, we treated 1-week HFD-fed mice with helminth antigens
from Schistosoma mansoni or Trichuris suis and evaluated whether the well-known
protective metabolic effects of helminth antigens involves BAT activation or
beiging. Indeed, antigens of both helminth species induced high numbers of
eosinophils in EpAT, but failed to induce beiging. In ScAT, Schistosoma mansoni
antigens induced mild eosinophilia, which was accompanied by slightly more
beiging. No effects were observed in BAT. To study type 2 responses on brown
adipocytes directly, T37i cells were stimulated with IL-4. This increased Ucp1
expression and strongly induced the production of eosinophil chemoattractant
CCL11 (+26-fold), revealing that brown adipocytes themselves can attract
eosinophils. Our findings indicate that helminth antigen-induced eosinophilia
fails to induce profound beiging of white adipocytes.
PMID- 28694302
TI - Up-regulation of ANKDR49, a poor prognostic factor, regulates cell proliferation
of gliomas.
AB - The Ankyrin repeat domain 49 (ANKRD49) is an evolutionarily conserved protein,
which is related to mediate protein-protein interaction. However, the function of
ANKRD49 in human glioma remains elusive. Mining through The Cancer Genome Atlas
(TCGA) database, we found that the expression of ANKRD49 was increased in glioma
tissues and that high expression of ANKRD49 was strongly associated with high
disease grade and poor overall survival. To investigate the role of ANKRD49 in
malignant glioma, lentivirus expressing shRNA targetting ANKRD49 was constructed
in U251 and U87 malignant glioma cells. We demonstrated that ANKRD49 knockdown
reduced the proliferation rate of U251 and U87 cells. Further mechanism analysis
indicated that depletion of ANKRD49 led to the cell-cycle arrest and induced
apoptosis in U251 and U87 cells. ANKRD49 knockdown also changed the expression of
key effectors that are involved in stress response, cell cycle, and apoptosis,
including p-HSP27 (heat shock protein 27), p-Smad2 (SMAD family member 2), p-p53,
p-p38, p-MAPK (mitogen-activated protein kinase), p-SAPK/JNK (stress-activated
protein kinase/c-jun n-terminal kinase), cleveagated Caspase-7, p-Chk1
(checkpoint kinase 1), and p-eIF2a (eukaryotic translation initiation factor 2a).
Taken together, our findings implicate that ANKRD49 promotes the proliferation of
human malignant glioma cells. ANKRD49 maybe an attractive target for malignant
glioma therapy.
PMID- 28694304
TI - Correction to "Molecular Cloning, Tissue Distribution, and Functional
Characterization of Marmoset Cytochrome P450 1A1, 1A2, and 1B1".
PMID- 28694305
TI - Insulin-Associated Weight Gain in Type 2 Diabetes Is Associated With Increases in
Sedentary Behavior.
PMID- 28694306
TI - UK adds hepatitis B to infant vaccination schedule.
PMID- 28694303
TI - Single-molecule fluorescence microscopy review: shedding new light on old
problems.
AB - Fluorescence microscopy is an invaluable tool in the biosciences, a genuine
workhorse technique offering exceptional contrast in conjunction with high
specificity of labelling with relatively minimal perturbation to biological
samples compared with many competing biophysical techniques. Improvements in
detector and dye technologies coupled to advances in image analysis methods have
fuelled recent development towards single-molecule fluorescence microscopy, which
can utilize light microscopy tools to enable the faithful detection and analysis
of single fluorescent molecules used as reporter tags in biological samples. For
example, the discovery of GFP, initiating the so-called 'green revolution', has
pushed experimental tools in the biosciences to a completely new level of
functional imaging of living samples, culminating in single fluorescent protein
molecule detection. Today, fluorescence microscopy is an indispensable tool in
single-molecule investigations, providing a high signal-to-noise ratio for
visualization while still retaining the key features in the physiological context
of native biological systems. In this review, we discuss some of the recent
discoveries in the life sciences which have been enabled using single-molecule
fluorescence microscopy, paying particular attention to the so-called 'super
resolution' fluorescence microscopy techniques in live cells, which are at the
cutting-edge of these methods. In particular, how these tools can reveal new
insights into long-standing puzzles in biology: old problems, which have been
impossible to tackle using other more traditional tools until the emergence of
new single-molecule fluorescence microscopy techniques.
PMID- 28694307
TI - Delivering timely surgery in Canadian hospitals.
PMID- 28694308
TI - Association of delay of urgent or emergency surgery with mortality and use of
health care resources: a propensity score-matched observational cohort study.
AB - BACKGROUND: Delay of surgery for hip fracture is associated with increased risk
of morbidity and mortality, but the effects of surgical delays on mortality and
resource use in the context of other emergency surgeries is poorly described. Our
objective was to measure the independent association between delay of emergency
surgery and in-hospital mortality, length of stay and costs. METHODS: We
identified all adult patients who underwent emergency noncardiac surgery between
January 2012 and October 2014 at a single tertiary care centre. Delay of surgery
was defined as the time from surgical booking to operating room entry exceeding
institutionally defined acceptable wait times, based on a standardized 5-level
priority system that accounted for surgery type and indication. Patients with
delayed surgery were matched to those without delay using propensity scores
derived from variables that accounted for details of admission and the hospital
stay, patient characteristics, physiologic instability, and surgical urgency and
risk. RESULTS: Of 15 160 patients, 2820 (18.6%) experienced a delay. The
mortality rates were 4.9% (138/2820) for those with delay and 3.2% (391/12 340)
for those without delay (odds ratio [OR] 1.59, 95% confidence interval [CI] 1.30
1.93). Within the propensity-matched cohort, delay was significantly associated
with mortality (OR 1.56, 95% CI 1.18-2.06), increased length of stay (incident
rate ratio 1.07, 95% CI 1.01-1.11) and higher total costs (incident rate ratio
1.06, 95% CI 1.01-1.11). INTERPRETATION: Delayed operating room access for
emergency surgery was associated with increased risk of inhospital mortality,
longer length of stay and higher costs. System issues appeared to underlie most
delays and must be addressed to improve the outcomes of emergency surgery.
PMID- 28694309
TI - Postpartum hypertension.
PMID- 28694310
TI - Stairlike fracture of the sternum.
PMID- 28694311
TI - Spoon versus knife.
PMID- 28694312
TI - Using thermography responsibly.
PMID- 28694313
TI - Underlying maternal infection likely cause of study findings.
PMID- 28694314
TI - The authors respond to "Underlying maternal infection likely cause of study
findings".
PMID- 28694315
TI - Half of Canadians can expect cancer diagnosis during lifetime.
PMID- 28694316
TI - Canadian women opting for less effective birth control.
PMID- 28694318
TI - Pulling together.
PMID- 28694317
TI - Family physicians support Open Pharma.
PMID- 28694319
TI - Margaret McCartney: An economist explains why healthcare can't be treated as a
market.
PMID- 28694320
TI - Authors' reply to Workman.
PMID- 28694321
TI - Lisa Anson: pharma's new figurehead wants to let light into the industry.
PMID- 28694322
TI - Phenotypic diversity drives paracrine drug tolerance.
PMID- 28694323
TI - A single mutation in Taiwanese H6N1 influenza hemagglutinin switches binding to
human-type receptors.
AB - In June 2013, the first case of human infection with an avian H6N1 virus was
reported in a Taiwanese woman. Although this was a single non-fatal case, the
virus continues to circulate in Taiwanese poultry. As with any emerging avian
virus that infects humans, there is concern that acquisition of human-type
receptor specificity could enable transmission in the human population. Despite
mutations in the receptor-binding pocket of the human H6N1 isolate, it has
retained avian-type (NeuAcalpha2-3Gal) receptor specificity. However, we show
here that a single nucleotide substitution, resulting in a change from Gly to Asp
at position 225 (G225D), completely switches specificity to human-type
(NeuAcalpha2-6Gal) receptors. Significantly, G225D H6 loses binding to chicken
trachea epithelium and is now able to bind to human tracheal tissue. Structural
analysis reveals that Asp225 directly interacts with the penultimate Gal of the
human-type receptor, stabilizing human receptor binding.
PMID- 28694324
TI - Patient-reported outcomes in hematology: is it time to focus more on them in
clinical trials and hematology practice?
AB - In less than 2 decades, major clinical advances have been made in various areas
of hematologic malignancies. Clinicians and patients now frequently face
challenging choices regarding various treatments that are often similar in regard
to safety or clinical effectiveness; hence, medical decision making has grown in
complexity. For example, several novel drugs have been developed as oral agents,
introducing an additional challenge in patient management, such as ensuring an
optimal adherence to therapy in order to maximize drug effectiveness. This
rapidly changing scenario provides a rationale for a more systematic collection
of patient-reported outcomes (PRO) in clinical research and routine care. In the
former case, PRO may help to better understand overall treatment effectiveness of
a new drug being tested. In the latter case, it may aid in making more informed,
individualized treatment decisions in daily practice by obtaining more accurate
information on the actual symptom burden experienced by the patient. In any case,
evaluating PRO requires making several, and often challenging, decisions
depending, for example, on the population being studied and the specific setting.
Therefore, if PROs are to fulfill their potential of generating clinically
meaningful data that robustly inform patient care, special attention should be
given to methodological rigor. We outline the value of a more systematic and
rigorous implementation of PRO assessment in the current hematology arena, by
providing some real world examples of how PRO data have contributed in better
understanding the value of new therapies. We also discuss practical
considerations in PRO assessment in clinical research.
PMID- 28694325
TI - TCR-CXCR4 signaling stabilizes cytokine mRNA transcripts via a PREX1-Rac1
pathway: implications for CTCL.
AB - As with many immunopathologically driven diseases, the malignant T cells of
cutaneous T-cell lymphomas (CTCLs), such as Sezary syndrome, display aberrant
cytokine secretion patterns that contribute to pathology and disease progression.
Targeting this disordered release of cytokines is complicated by the changing
cytokine milieu that drives the phenotypic changes of CTCLs. Here, we
characterize a novel signaling pathway that can be targeted to inhibit the
secretion of cytokines by modulating either CXCR4 or CXCR4-mediated signaling. We
demonstrate that upon ligation of the T-cell antigen receptor (TCR), the TCR
associates with and transactivates CXCR4 via phosphorylation of S339-CXCR4 in
order to activate a PREX1-Rac1-signaling pathway that stabilizes interleukin-2(IL
2), IL-4, and IL-10 messenger RNA (mRNA) transcripts. Pharmacologic inhibition of
either TCR-CXCR4 complex formation or PREX1-Rac1 signaling in primary human T
cells decreased mRNA stability and inhibited secretion of IL-2, IL-4, and IL-10.
Applying this knowledge to Sezary syndrome, we demonstrate that targeting various
aspects of this signaling pathway blocks both TCR-dependent and TCR-independent
cytokine secretion from a Sezary syndrome-derived cell line and patient isolates.
Together, these results identify multiple aspects of a novel TCR-CXCR4-signaling
pathway that could be targeted to inhibit the aberrant cytokine secretion that
drives the immunopathogenesis of Sezary syndrome and other immunopathological
diseases.
PMID- 28694326
TI - Genomic analysis of 220 CTCLs identifies a novel recurrent gain-of-function
alteration in RLTPR (p.Q575E).
AB - Cutaneous T-cell lymphoma (CTCL) is an incurable non-Hodgkin lymphoma of the skin
homing T cell. In early-stage disease, lesions are limited to the skin, but in
later-stage disease, the tumor cells can escape into the blood, the lymph nodes,
and at times the visceral organs. To clarify the genomic basis of CTCL, we
performed genomic analysis of 220 CTCLs. Our analyses identify 55 putative driver
genes, including 17 genes not previously implicated in CTCL. These novel
mutations are predicted to affect chromatin (BCOR, KDM6A, SMARCB1, TRRAP), immune
surveillance (CD58, RFXAP), MAPK signaling (MAP2K1, NF1), NF-kappaB signaling
(PRKCB, CSNK1A1), PI-3-kinase signaling (PIK3R1, VAV1), RHOA/cytoskeleton
remodeling (ARHGEF3), RNA splicing (U2AF1), T-cell receptor signaling (PTPRN2,
RLTPR), and T-cell differentiation (RARA). Our analyses identify recurrent
mutations in 4 genes not previously identified in cancer. These include CK1alpha
(encoded by CSNK1A1) (p.S27F; p.S27C), PTPRN2 (p.G526E), RARA (p.G303S), and
RLTPR (p.Q575E). Last, we functionally validate CSNK1A1 and RLTPR as putative
oncogenes. RLTPR encodes a recently described scaffolding protein in the T-cell
receptor signaling pathway. We show that RLTPR (p.Q575E) increases binding of
RLTPR to downstream components of the NF-kappaB signaling pathway, selectively
upregulates the NF-kappaB pathway in activated T cells, and ultimately augments T
cell-receptor-dependent production of interleukin 2 by 34-fold. Collectively, our
analysis provides novel insights into CTCL pathogenesis and elucidates the
landscape of potentially targetable gene mutations.
PMID- 28694327
TI - Efficacy of nutritional interventions to lower circulating ceramides in young
adults: FRUVEDomic pilot study.
AB - The 2010 USDA Dietary Guidelines for Americans (DGA) recommends a diet largely
composed of fruit and vegetables. Consuming a diet high in fruit and vegetables
and low in refined carbohydrates and saturated fat may reduce an individual's
risk for type 2 diabetes, nonalcoholic fatty liver disease, low-grade chronic
inflammation, and metabolic syndrome (MetS). Several recent studies have
implicated the bioactive sphingolipid ceramide as an associative and causative
biomarker for the development of these conditions. Considering that the intake of
fruit and vegetables is frequently inadequate in young adults, we performed a
pilot investigation to assess the efficacy of a free-living fruit and vegetable
intervention on overall metabolic health, circulating ceramide supply, and
inflammatory status in young adults. We discovered that adoption of the
recommended DGA for fruit and vegetable intake for 8 weeks decreased waist
circumference, systolic blood pressure, and circulating cholesterol. Lipidomics
analysis revealed that nutritional intervention can lower circulating ceramides,
including C24:0 ceramide, a known inhibitor of insulin signaling. Unexpectedly,
we observed an increase in C16:0 ceramide, suggesting that this form of ceramide
in circulation is not associated with metabolic disease in humans. We also
observed an improved inflammatory status with enhanced fruit and vegetable intake
that was correlated with ceramide concentrations. These data suggest that
adopting the recommended DGA is associated with a reduction of many, but not all,
ceramide species and may help to prevent or mitigate MetS. Future research needs
to assess whether the ceramide-lowering ability of nutritional intervention is
associated with reduced risk of developing metabolic disease.
PMID- 28694328
TI - The contribution of the C5 protein subunit of Escherichia coli ribonuclease P to
specificity for precursor tRNA is modulated by proximal 5' leader sequences.
AB - Recognition of RNA by RNA processing enzymes and RNA binding proteins often
involves cooperation between multiple subunits. However, the interdependent
contributions of RNA and protein subunits to molecular recognition by
ribonucleoproteins are relatively unexplored. RNase P is an endonuclease that
removes 5' leaders from precursor tRNAs and functions in bacteria as a dimer
formed by a catalytic RNA subunit (P RNA) and a protein subunit (C5 in E. coli).
The P RNA subunit contacts the tRNA body and proximal 5' leader sequences [N(-1)
and N(-2)] while C5 binds distal 5' leader sequences [N(-3) to N(-6)]. To
determine whether the contacts formed by P RNA and C5 contribute independently to
specificity or exhibit cooperativity or anti-cooperativity, we compared the
relative kcat/Km values for all possible combinations of the six proximal 5'
leader nucleotides (n = 4096) for processing by the E. coli P RNA subunit alone
and by the RNase P holoenzyme. We observed that while the P RNA subunit shows
specificity for 5' leader nucleotides N(-2) and N(-1), the presence of the C5
protein reduces the contribution of P RNA to specificity, but changes specificity
at N(-2) and N(-3). The results reveal that the contribution of C5 protein to
RNase P processing is controlled by the identity of N(-2) in the pre-tRNA 5'
leader. The data also clearly show that pairing of the 5' leader with the 3' ACCA
of tRNA acts as an anti-determinant for RNase P cleavage. Comparative analysis of
genomically encoded E. coli tRNAs reveals that both anti-determinants are subject
to negative selection in vivo.
PMID- 28694329
TI - Feminization of male mouse liver by persistent growth hormone stimulation:
Activation of sex-biased transcriptional networks and dynamic changes in
chromatin states.
AB - Sex-dependent pituitary GH secretory profiles--pulsatile in males and persistent
in females--regulate sex-biased, STAT5-dependent expression of hundreds of genes
in mouse liver, imparting sex differences in hepatic drug/lipid metabolism and
disease risk. Here we examine transcriptional and epigenetic changes induced by
continuous-GH infusion (cGH) in male mice, which rapidly feminizes the temporal
profile of liver STAT5 activity. cGH repressed 86% of male-biased genes and
induced 68% of female-biased genes within 4-days; however, several highly female
specific genes showed weak or no feminization, even after 14-days cGH. Female
biased genes already in an active chromatin state in male liver generally showed
early cGH responses; genes in an inactive chromatin state often responded late.
Early cGH-responsive genes included those encoding two GH/STAT5-regulated
transcriptional repressors: male-biased BCL6, which was repressed, and female
specific CUX2, which was induced. Male-biased genes activated by STAT5 and/or
repressed by CUX2 were enriched for early cGH repression. Female-biased BCL6
targets were enriched for early cGH de-repression. Changes in sex-specific
chromatin accessibility and histone modifications accompanied these cGH-induced
sex-biased gene expression changes. Thus, the temporal, sex-biased gene responses
to persistent GH stimulation are dictated by GH/STAT5-regulated transcription
factors arranged in a hierarchical network and by the dynamics of changes in sex
biased epigenetic states.
PMID- 28694330
TI - Phosphorylation of the C-Raf N-region promotes Raf dimerization.
AB - Activation of Raf kinases by the small GTPase Ras requires two major sets of
phosphorylations. One set lies within the activation loop and the other lies
within the N-terminal acidic region (N-region). In the most abundant isoform of
Raf, C-Raf, N-region phosphorylations occur on serine 338 (S338) and tyrosine 341
(Y341), and are thought to provide allosteric activation of the Raf dimer. We
show that the phosphorylation of these N-region sites does not require C-Raf
dimerization, but rather, they precede dimerization. One of these
phosphorylations (phospho-Y341) is required for C-Raf dimerization and this
action can be replicated by phosphomimetic mutants both in vivo and in vitro The
role of phosphorylation of Y341 in promoting Raf dimerization is distinct from
its well-known function to facilitate S338 phosphorylation.In Ras-mutant
pancreatic cancer cell lines, phosphorylation and dimerization of C-Raf is
basally elevated. Dimerization is thought to contribute to their elevated growth
rate through their activation of the MAP kinase (ERK) signaling cascade. Blocking
tyrosine phosphorylation of C-Raf with Src family inhibitors blocks the growth,
basal dimerization, and ERK activation in these cells. We suggest that the
kinases mediating C-Raf Y341 phosphorylation are potential candidate drug targets
in selected Ras-dependent cancers.
PMID- 28694331
TI - Transcriptional Elongation Control of Hepatitis B Virus Covalently Closed
Circular DNA Transcription by Super Elongation Complex and BRD4.
AB - Chronic hepatitis B virus (HBV) infection can lead to liver cirrhosis and
hepatocellular carcinoma. HBV reactivation during or after chemotherapy is a
potentially fatal complication for cancer patients with chronic HBV infection.
Transcription of HBV is a critical intermediate step of the HBV life cycle.
However, factors controlling HBV transcription remain largely unknown. Here, we
found that different P-TEFb complexes are involved in the transcription of the
HBV viral genome. Both BRD4 and the super elongation complex (SEC) bind to the
HBV genome. The treatment of bromodomain inhibitor JQ1 stimulates HBV
transcription and increases the occupancy of BRD4 on the HBV genome, suggesting
the bromodomain-independent recruitment of BRD4 to the HBV genome. JQ1 also leads
to the increased binding of SEC to the HBV genome, and SEC is required for JQ1
induced HBV transcription. These findings reveal a novel mechanism by which the
HBV genome hijacks the host P-TEFb-containing complexes to promote its own
transcription. Our findings also point out an important clinical implication,
that is, the potential risk of HBV reactivation during therapy with a BRD4
inhibitor, such as JQ1 or its analogues, which are a potential treatment for
acute myeloid leukemia.
PMID- 28694332
TI - The Ets2 Repressor Factor (Erf) Is Required for Effective Primitive and
Definitive Hematopoiesis.
AB - Erf is a gene for a ubiquitously expressed Ets DNA-binding domain-containing
transcriptional repressor. Erf haploinsufficiency causes craniosynostosis in
humans and mice, while its absence in mice leads to failed chorioallantoic fusion
and death at embryonic day 10.5 (E10.5). In this study, we show that Erf is
required in all three waves of embryonic hematopoiesis. Mice lacking Erf in the
embryo proper exhibited severe anemia and died around embryonic day 14.5. Erf
epiblast-specific knockout embryos had reduced numbers of circulating blood cells
from E9.5 onwards, with the development of severe anemia by E14.5. Elimination of
Erf resulted in both reduced and more immature primitive erythroblasts at E9.5 to
E10.5. Reduced definitive erythroid colony-forming activity was found in the
bloodstream of E10.5 embryos and in the fetal liver at E11.5 to E13.5. Finally,
elimination of Erf resulted in impaired repopulation ability, indicating that Erf
is necessary for hematopoietic stem cell maintenance or differentiation. We
conclude that Erf is required for both primitive and erythromyeloid progenitor
waves of hematopoietic stem cell (HSC)-independent hematopoiesis as well as for
the normal function of HSCs.
PMID- 28694333
TI - EPC1/TIP60-Mediated Histone Acetylation Facilitates Spermiogenesis in Mice.
AB - Global histone hyperacetylation is suggested to play a critical role for
replacement of histones by transition proteins and protamines to compact the
genome during spermiogenesis. However, the underlying mechanisms for
hyperacetylation-mediated histone replacement remains poorly understood. Here, we
report that EPC1 and TIP60, two critical components of the mammalian nucleosome
acetyltransferase of H4 (NuA4) complexes, are coexpressed in male germ cells.
Strikingly, genetic ablation of either Epc1 or Tip60 disrupts hyperacetylation
and impairs histone replacement, in turn causing aberrant spermatid development.
Taking these observations together, we reveal an essential role of the NuA4
complexes for histone hyperacetylation and subsequent compaction of the spermatid
genome.
PMID- 28694334
TI - Loss of Tuberous Sclerosis Complex1 in Adult Oligodendrocyte Progenitor Cells
Enhances Axon Remyelination and Increases Myelin Thickness after a Focal
Demyelination.
AB - Although the mammalian target of rapamycin (mTOR) is an essential regulator of
developmental oligodendrocyte differentiation and myelination, oligodendrocyte
specific deletion of tuberous sclerosis complex (TSC), a major upstream inhibitor
of mTOR, surprisingly also leads to hypomyelination during CNS development.
However, the function of TSC has not been studied in the context of
remyelination. Here, we used the inducible Cre-lox system to study the function
of TSC in the remyelination of a focal, lysolecithin-demyelinated lesion in adult
male mice. Using two different mouse models in which Tsc1 is deleted by Cre
expression in oligodendrocyte progenitor cells (OPCs) or in premyelinating
oligodendrocytes, we reveal that deletion of Tsc1 affects oligodendroglia
differently depending on the stage of the oligodendrocyte lineage. Tsc1 deletion
from NG2+ OPCs accelerated remyelination. Conversely, Tsc1 deletion from
proteolipid protein (PLP)-positive oligodendrocytes slowed remyelination.
Contrary to developmental myelination, there were no changes in OPC or
oligodendrocyte numbers in either model. Our findings reveal a complex role for
TSC in oligodendrocytes during remyelination in which the timing of Tsc1 deletion
is a critical determinant of its effect on remyelination. Moreover, our findings
suggest that TSC has different functions in developmental myelination and
remyelination.SIGNIFICANCE STATEMENT Myelin loss in demyelinating disorders such
as multiple sclerosis results in disability due to loss of axon conductance and
axon damage. Encouragingly, the nervous system is capable of spontaneous
remyelination, but this regenerative process often fails. Many chronically
demyelinated lesions have oligodendrocyte progenitor cells (OPCs) within their
borders. It is thus of great interest to elucidate mechanisms by which we might
enhance endogenous remyelination. Here, we provide evidence that deletion of Tsc1
from OPCs, but not differentiating oligodendrocytes, is beneficial to
remyelination. This finding contrasts with the loss of oligodendroglia and
hypomyelination seen with Tsc1 or Tsc2 deletion in the oligodendrocyte lineage
during CNS development and points to important differences in the regulation of
developmental myelination and remyelination.
PMID- 28694335
TI - Prior Cocaine Self-Administration Increases Response-Outcome Encoding That Is
Divorced from Actions Selected in Dorsal Lateral Striatum.
AB - Dorsal lateral striatum (DLS) is a highly associative structure that encodes
relationships among environmental stimuli, behavioral responses, and predicted
outcomes. DLS is known to be disrupted after chronic drug abuse; however, it
remains unclear what neural signals in DLS are altered. Current theory suggests
that drug use enhances stimulus-response processing at the expense of response
outcome encoding, but this has mostly been tested in simple behavioral tasks.
Here, we investigated what neural correlates in DLS are affected by previous
cocaine exposure as rats performed a complex reward-guided decision-making task
in which predicted reward value was independently manipulated by changing the
delay to or size of reward associated with a response direction across a series
of trial blocks. After cocaine self-administration, rats exhibited stronger
biases toward higher-value reward and firing in DLS more strongly represented
action-outcome contingencies independent from actions subsequently taken rather
than outcomes predicted by selected actions (chosen-outcome contingencies) and
associations between stimuli and actions (stimulus-response contingencies). These
results suggest that cocaine self-administration strengthens action-outcome
encoding in rats (as opposed to chosen-outcome or stimulus-response encoding),
which abnormally biases behavior toward valued reward when there is a choice
between two options during reward-guided decision-making.SIGNIFICANCE STATEMENT
Current theories suggest that the impaired decision-making observed in
individuals who chronically abuse drugs reflects a decrease in goal-directed
behaviors and an increase in habitual behaviors governed by neural
representations of response-outcome (R-O) and stimulus-response associations,
respectively. We examined the impact that prior cocaine self-administration had
on firing in dorsal lateral striatum (DLS), a brain area known to be involved in
habit formation and affected by drugs of abuse, during performance of a complex
reward-guided decision-making task. Surprisingly, we found that previous cocaine
exposure enhanced R-O associations in DLS. This suggests that there may be more
complex consequences of drug abuse than current theories have explored,
especially when examining brain and behavior in the context of a complex two
choice decision-making task.
PMID- 28694336
TI - Magnified Neural Envelope Coding Predicts Deficits in Speech Perception in Noise.
AB - Verbal communication in noisy backgrounds is challenging. Understanding speech in
background noise that fluctuates in intensity over time is particularly difficult
for hearing-impaired listeners with a sensorineural hearing loss (SNHL). The
reduction in fast-acting cochlear compression associated with SNHL exaggerates
the perceived fluctuations in intensity in amplitude-modulated sounds. SNHL
induced changes in the coding of amplitude-modulated sounds may have a
detrimental effect on the ability of SNHL listeners to understand speech in the
presence of modulated background noise. To date, direct evidence for a link
between magnified envelope coding and deficits in speech identification in
modulated noise has been absent. Here, magnetoencephalography was used to
quantify the effects of SNHL on phase locking to the temporal envelope of
modulated noise (envelope coding) in human auditory cortex. Our results show that
SNHL enhances the amplitude of envelope coding in posteromedial auditory cortex,
whereas it enhances the fidelity of envelope coding in posteromedial and
posterolateral auditory cortex. This dissociation was more evident in the right
hemisphere, demonstrating functional lateralization in enhanced envelope coding
in SNHL listeners. However, enhanced envelope coding was not perceptually
beneficial. Our results also show that both hearing thresholds and, to a lesser
extent, magnified cortical envelope coding in left posteromedial auditory cortex
predict speech identification in modulated background noise. We propose a
framework in which magnified envelope coding in posteromedial auditory cortex
disrupts the segregation of speech from background noise, leading to deficits in
speech perception in modulated background noise.SIGNIFICANCE STATEMENT People
with hearing loss struggle to follow conversations in noisy environments.
Background noise that fluctuates in intensity over time poses a particular
challenge. Using magnetoencephalography, we demonstrate anatomically distinct
cortical representations of modulated noise in normal-hearing and hearing
impaired listeners. This work provides the first link among hearing thresholds,
the amplitude of cortical representations of modulated sounds, and the ability to
understand speech in modulated background noise. In light of previous work, we
propose that magnified cortical representations of modulated sounds disrupt the
separation of speech from modulated background noise in auditory cortex.
PMID- 28694337
TI - Targeted Memory Reactivation during Sleep Adaptively Promotes the Strengthening
or Weakening of Overlapping Memories.
AB - System memory consolidation is conceptualized as an active process whereby newly
encoded memory representations are strengthened through selective memory
reactivation during sleep. However, our learning experience is highly overlapping
in content (i.e., shares common elements), and memories of these events are
organized in an intricate network of overlapping associated events. It remains to
be explored whether and how selective memory reactivation during sleep has an
impact on these overlapping memories acquired during awake time. Here, we test in
a group of adult women and men the prediction that selective memory reactivation
during sleep entails the reactivation of associated events and that this may lead
the brain to adaptively regulate whether these associated memories are
strengthened or pruned from memory networks on the basis of their relative
associative strength with the shared element. Our findings demonstrate the
existence of efficient regulatory neural mechanisms governing how complex memory
networks are shaped during sleep as a function of their associative memory
strength.SIGNIFICANCE STATEMENT Numerous studies have demonstrated that system
memory consolidation is an active, selective, and sleep-dependent process in
which only subsets of new memories become stabilized through their reactivation.
However, the learning experience is highly overlapping in content and thus events
are encoded in an intricate network of related memories. It remains to be
explored whether and how memory reactivation has an impact on overlapping
memories acquired during awake time. Here, we show that sleep memory reactivation
promotes strengthening and weakening of overlapping memories based on their
associative memory strength. These results suggest the existence of an efficient
regulatory neural mechanism that avoids the formation of cluttered memory
representation of multiple events and promotes stabilization of complex memory
networks.
PMID- 28694338
TI - No Effect of Commercial Cognitive Training on Brain Activity, Choice Behavior, or
Cognitive Performance.
AB - Increased preference for immediate over delayed rewards and for risky over
certain rewards has been associated with unhealthy behavioral choices. Motivated
by evidence that enhanced cognitive control can shift choice behavior away from
immediate and risky rewards, we tested whether training executive cognitive
function could influence choice behavior and brain responses. In this randomized
controlled trial, 128 young adults (71 male, 57 female) participated in 10 weeks
of training with either a commercial web-based cognitive training program or web
based video games that do not specifically target executive function or adapt the
level of difficulty throughout training. Pretraining and post-training,
participants completed cognitive assessments and functional magnetic resonance
imaging during performance of the following validated decision-making tasks:
delay discounting (choices between smaller rewards now vs larger rewards in the
future) and risk sensitivity (choices between larger riskier rewards vs smaller
certain rewards). Contrary to our hypothesis, we found no evidence that cognitive
training influences neural activity during decision-making; nor did we find
effects of cognitive training on measures of delay discounting or risk
sensitivity. Participants in the commercial training condition improved with
practice on the specific tasks they performed during training, but participants
in both conditions showed similar improvement on standardized cognitive measures
over time. Moreover, the degree of improvement was comparable to that observed in
individuals who were reassessed without any training whatsoever. Commercial
adaptive cognitive training appears to have no benefits in healthy young adults
above those of standard video games for measures of brain activity, choice
behavior, or cognitive performance.SIGNIFICANCE STATEMENT Engagement of neural
regions and circuits important in executive cognitive function can bias
behavioral choices away from immediate rewards. Activity in these regions may be
enhanced through adaptive cognitive training. Commercial brain training programs
claim to improve a broad range of mental processes; however, evidence for
transfer beyond trained tasks is mixed. We undertook the first randomized
controlled trial of the effects of commercial adaptive cognitive training
(Lumosity) on neural activity and decision-making in young adults (N = 128)
compared with an active control (playing on-line video games). We found no
evidence for relative benefits of cognitive training with respect to changes in
decision-making behavior or brain response, or for cognitive task performance
beyond those specifically trained.
PMID- 28694339
TI - Temporal changes in predicted risk of type 2 diabetes in Germany: findings from
the German Health Interview and Examination Surveys 1997-1999 and 2008-2011.
AB - OBJECTIVE: Over time, prevalence changes in individual diabetes risk factors have
been observed for Germany and other European countries. We aimed to investigate
the temporal change of a summary measure of type 2 diabetes risk in Germany.
DESIGN: Comparison of data from two cross-sectional surveys that are about 12
years apart. SETTING: Two nationwide health examination surveys representative
for the non-institutionalised population aged 18-79 years in Germany.
PARTICIPANTS: The study included participants without diagnosed diabetes from the
national health examination surveys in 1997-1999 (n=6457) and 2008-2011 (n=6095).
OUTCOME MEASURES: Predicted 5-year type 2 diabetes risk was calculated using the
German Diabetes Risk Score (GDRS), which considers information on age,
anthropometry, lifestyle factors, hypertension and family history of diabetes.
RESULTS: Between the two survey periods, the overall age- and sex-standardised
predicted 5-year risk of type 2 diabetes decreased by 27% from 1.5% (95% CI 1.4%
to 1.6%) to 1.1% (1.0% to 1.2%). The decrease in red meat intake and waist
circumference had the highest impact on the overall decrease in diabetes risk. In
stratified analyses, diabetes risk decreased among both sexes and within strata
of age and body mass index. Diabetes risk also decreased among highly educated
persons, but remained unchanged among persons with a middle or low educational
level. CONCLUSIONS: Monitoring type 2 diabetes risk by a summary measure such as
the GDRS could essentially contribute to interpret the dynamics in diabetes
epidemiology.
PMID- 28694340
TI - Colonisation of Irish patients with chronic obstructive pulmonary disease by
Streptococcus pneumoniae and analysis of the pneumococcal vaccine coverage: a non
interventional, observational, prospective cohort study.
AB - OBJECTIVES: To characterise the pattern of colonisation and serotypes of
Streptococcus pneumoniae among patients with chronic obstructive pulmonary
disease (COPD) who currently receive the 23-valent pneumococcal polysaccharide
vaccine (PPV-23) according to vaccination status, use of antibiotics and
steroids. To investigate the prevalence of PPV-23 and 13-valent pneumococcal
conjugate vaccine (PCV-13) serotypes within the study cohort. DESIGN: A non
interventional, observational, prospective cohort study with a 12 -month follow
up period inclusive of quarterly study visits. SETTING: Beaumont Hospital and The
Royal College of Surgeons in Ireland Clinical Research Centre, Dublin, Ireland.
PARTICIPANTS: Patients with an established diagnosis of COPD attending a tertiary
medical centre. PRIMARY OUTCOME MEASURE: Colonisation rate of S. pneumoniae in
patients with COPD and characterisation of serotypes of S. pneumoniae with
correlation to currently available pneumococcal vaccines. Sputum and
oropharyngeal swab samples were collected for the isolation of S. pneumoniae.
SECONDARY OUTCOME MEASURE: Seasonality of colonisation of S. pneumoniae and its
relationship with the incidence of exacerbations of COPD. RESULTS: S. pneumoniae
was detected in 16 of 417 samples, a colonisation incident rate of 3.8% and in 11
of 133 (8%) patients at least once during the study. The majority of S.
pneumoniae isolates were identified in spring and were non-vaccine serotypes for
either the PPV-23 or PCV-13 (63%). The colonisation incident rate of S.
pneumoniae fluctuated over the four seasons with a peak of 6.6% in spring and the
lowest rate of 2.2% occurring during winter. Antibiotic use was highest during
periods of low colonisation. CONCLUSIONS: There is seasonal variation in S.
pneumoniae colonisation among patients with COPD which may reflect antibiotic use
in autumn and winter. The predominance of non-vaccine types suggests that PCV-13
may have limited impact among patients with COPD in Ireland who currently receive
PPV-23. TRIAL REGISTRATION NUMBER: NCT02535546; post-results.
PMID- 28694341
TI - Open reduction and internal fixation of humeral shaft fractures versus
conservative treatment with a functional brace: a study protocol of a randomised
controlled trial embedded in a cohort.
AB - INTRODUCTION: Humeral shaft fractures represent 1%-3% of all fractures and 20% of
humeral fractures in adults. The treatment of these fractures is mainly
conservative and operative treatment is usually reserved for specific
circumstances. To date, no randomised controlled trial (RCT) has compared
operative treatment of humeral shaft fractures with conservative treatment.
METHODS AND ANALYSIS: We will conduct an RCT to compare the effectiveness and
cost-effectiveness of surgical and conservative treatment of humeral shaft
fractures. After providing informed consent, 80 patients from 18 years of age
with humeral shaft fracture will be randomly assigned to open reduction and
internal fixation with locking plate or conservative treatment with functional
bracing. We will follow the patients for 10 years and compare the results at
different time points. The primary outcome will be Disabilities of Arm, Shoulder
and Hand (DASH) at 12 months. The secondary outcomes will include Numerical
Rating Scale for pain at rest and in activities, Constant Score and quality of
life instrument 15D. Patients not willing to participate in the RCT will be asked
to participate in a prospective cohort follow-up study, 'the declined cohort'.
This cohort will be followed up at the same time points as the randomised
patients to assess the potential effect of participation bias on RCT results and
to enhance the external validity of the RCT. In one of the recruiting centres,
all cooperative patients with humeral shaft fractures not eligible for
randomisation will be asked to participate in a 'non-eligible cohort' study. We
will use blinded data interpretation of the randomised cohort to avoid biased
interpretation of outcomes. Our null hypothesis is that there is no clinically
relevant difference in the primary outcome measure between the two treatment
groups. We will consider a difference of a minimum of 10 points in DASH
clinically relevant. ETHICS AND DISSEMINATION: The institutional review board of
the Helsinki and Uusimaa Hospital District has approved the protocol. We will
disseminate the findings of this study through peer-reviewed publications and
conference presentations. TRIAL REGISTRATION NUMBER: NCT01719887; pre-results.
PMID- 28694342
TI - Normative visual acuity in Chinese preschoolers aged 36 to <48 months as measured
with the linear HOTV chart: the Yuhuatai Pediatric Eye Disease Study.
AB - OBJECTIVES: To document population-based normative data for uncorrected visual
acuity (UCVA) in Chinese preschoolers aged 36 to <48 months without any sight
affecting abnormalities and to evaluate its effectiveness for vision referral.
METHODS: In a population-based cohort of children in the Yuhuatai Pediatric Eye
Disease Study, UCVA was measured by using the linear HOTV chart, followed by
other ocular examinations. Reference population was defined as children without
ophthalmic abnormalities or refractive error. Normative UCVA was obtained from
the reference population. The UCVA referral cut-off was defined as the lowest
fifth percentile of the normative distribution of UCVA. RESULTS: The analysis
cohort consisted of 1606 Chinese preschoolers aged 36 to <48 months. Among them,
a total of 791 children were included in the reference population. The 5th, 50th
and 95th percentiles of the UCVA distribution in the reference population were
20/40, 20/32 and 20/25, respectively. UCVA improved with increasing age
(p<0.0001), but worsen if prematurity was presented (p=0.041). Using the fifth
percentile, UCVA cut-off from the reference population generated referral rates
of 26.9% in the general population, and detected more than 86% of amblyopia
cases. CONCLUSIONS: We propose that UCVA no better than 20/40 measured by linear
HOTV chart should be a referral cut-off for Chinese preschoolers aged 36 to <48
months. Most amblyopia cases can be identified with this age-specific and chart
specific UCVA cut-off.
PMID- 28694343
TI - Non-withdrawal of beta blockers in acute decompensated chronic and de novo heart
failure with reduced ejection fraction in a prospective multicentre study of
patients with acute heart failure in the Middle East.
AB - OBJECTIVES: Beta blockers reduce mortality in heart failure (HF). However, it is
not clear whether they should be temporarily withdrawn during acute HF. DESIGN:
Analysis of prospectively collected data. SETTING: The Gulf aCute heArt failuRe
rEgistry is a prospective multicentre study of patients hospitalised with acute
HF in seven Middle Eastern countries. PARTICIPANTS: 5005 patients with acute HF.
OUTCOME MEASURES: We studied the effect of beta blockers non-withdrawal on
intrahospital, 3-month and 12-month mortality and rehospitalisation for HF in
patients with acute decompensated chronic heart failure (ADCHF) and acute de novo
heart failure (ADNHF) and a left ventricular ejection fraction (LVEF) <40%.
RESULTS: 44.1% of patients were already on beta blockers on inclusion. Among
those, 57.8% had an LVEF <40%. Further, 79.9% were diagnosed with ADCHF and 20.4%
with ADNHF. Mean age was 61 (SD 13.9) in the ADCHF group and 59.8 (SD 13.8) in
the ADNHF group. Intrahospital mortality was lower in patients whose beta blocker
therapy was not withdrawn in both the ADCHF and ADNHF groups. This protective
effect persisted after multivariate analysis (OR 0.05, 95% CI 0.022 to 0.112; OR
0.018, 95% CI 0.003 to 0.122, respectively, p<0.001 for both) and propensity
score matching even after correcting for variables that remained significant in
the new model (OR 0.084, 95% CI 0.015 to 0.468, p=0.005; OR 0.047, 95% CI 0.013
to 0.169, p<0.001, respectively). At 3 months, mortality was still lower only in
patients with ADCHF in whom beta blockers were maintained during initial
hospitalisation. However, the benefit was lost after correcting for confounding
factors. Interestingly, rehospitalisation for HF and length of hospital stay were
unaffected by beta blockers discontinuation in all patients. CONCLUSION: In
summary, non-withdrawal of beta blockers in acute decompensated chronic and de
novo heart failure with reduced ejection fraction is associated with lower
intrahospital mortality but does not influence 3-month and 12-month mortality,
rehospitalisation for heart failure,and the length of hospital stay. TRIAL
REGISTRATION NUMBER: NCT01467973; Post-results.
PMID- 28694344
TI - Prevalence of pregnancy-related complications and course of labour of surviving
women who gave birth in selected health facilities in Rwanda: a health facility
based, cross-sectional study.
AB - OBJECTIVES: This study estimated health facility-based prevalence for pre
eclampsia/eclampsia, postpartum haemorrhage and caesarean section (CS) due to
prolonged labour/dystocia. The background characteristics of Rwandan pregnant
women, the course of labour and the level of healthcare were investigated in
relation to pregnancy and delivery outcomes. METHODS: This is health facility
based study and data were collected in 2014-2015 through structured interviews
and medical records (n=817) in Kigali and Northern Province, Rwanda. Frequencies
and prevalence were used to describe participants' background factors, labour and
delivery-related characteristics. Bivariable and multivariable logistic
regression models were performed for different background factors and
pregnancy/delivery outcomes. RESULTS: Pre-eclampsia/eclampsia, postpartum
haemorrhage and CS due to prolonged labour/dystocia represented 1%, 2.7% and 5.4%
of all participants, respectively. In total, 56.4% of the participants were
transferred from facilities with low levels to those with higher levels of
healthcare, and the majority were transferred from health centres to district
hospitals, with CS as the main reason for transfer. Participants who arrived at
the health facility with cervical dilation grade of <=3 cm spent more hours in
maternity ward than those who arrived with cervical dilatation grade of >=4 cm.
Risk factors for CS due to prolonged labour or dystocia were poor households,
nulliparity and residence far from health facility. CONCLUSIONS: The estimated
health facility-based prevalence of pregnancy-related complications was
relatively low in this sample from Rwanda. CS was the main reason for the
transfer of pregnant women from health centres to district hospitals. Upgrading
the capacity of health centres in the management of pregnant women in Rwanda may
improve maternal and fetal health.
PMID- 28694345
TI - Facilitating mental health help-seeking by young adults with a dedicated online
program: a feasibility study of Link.
AB - OBJECTIVE: To explore the feasibility of a dedicated online youth mental health
help-seeking intervention and to evaluate using a randomised controlled trial
(RCT) study design in order to identify any modifications needed before
commencement of the full-scale RCT. DESIGN: A pilot RCT with 1:1 randomisation to
either the intervention or comparison arm. SETTING: An online study conducted
Australia-wide. PARTICIPANTS: 18-25 year olds living in Australia were recruited
via social media. INTERVENTION: Link is a dedicated online mental health help
seeking navigation tool that matches user's mental health issues, severity and
service-type preferences (online, phone and face-to-face) with appropriate youth
friendly services. The comparison arm was usual help-seeking strategies with a
link to Google.com. MAIN OUTCOME MEASURES: The primary outcome was the number of
acceptability and feasibility criteria successfully met. Intervention and study
design acceptability and feasibility were assessed by nine criteria. Secondary
outcomes, via online surveys (at baseline, 1 week and 1 month) measured service
use, help-seeking intentions, psychological distress, barriers to help-seeking,
attitudes towards mental health help-seeking, mental health literacy,
satisfaction and trust. RESULTS: Fifty-one participants were randomised
(intervention: n=24; comparison: n=27). Three out of four of the intervention and
two out of five of the study design criteria were met. Unmet criteria could be
addressed by modifications to the study design. Qualitative analysis demonstrated
that Link was useful to participants and may have increased their positive
experiences towards help-seeking. There were no observable differences between
arms in any outcome measures and no harms were detected. CONCLUSION: Generally,
the Link intervention and study design were acceptable and feasible with
modifications suggested for the four out of nine unmet criteria. The main trial
will hence have shorter surveys and a simpler recruitment process, use positive
affect as the primary outcome and will not link to Google.com for the comparison
arm. TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry,
ACTRN12614000386639.
PMID- 28694346
TI - A systematic review of the worldwide prevalence of survivors of poliomyelitis
reported in 31 studies.
AB - BACKGROUND: Accurate prevalence figures estimating the number of survivors of
poliomyelitis (disease causing acute flaccid paralysis) following poliovirus
infection are not available. We aim to undertake a systematic review of all
literature concerning the prevalence of survivors of poliomyelitis. METHODS:
Electronic databases were searched from 1900 up to May 2016 for peer-reviewed
studies using a population-based approach witha defined denominator and some form
of diagnostic or clinical verification of polio. Exclusion criteria were any
prevalence data that were unable to be extracted or calculated and studies
reporting on incidence only. The quality of each included study was assessed
using an existing tool modified for use in prevalence studies. Average crude
prevalence rates were used to calculate worldwide estimates. RESULTS: Thirty-one
studies met criteria with 90% of studies conducted in low-income to lower middle
income countries. Significant variability in the prevalence of survivors of
poliomyelitis was revealed, in low- income to lower middle-income (15 per 100 000
in Nigeria to 1733 in India) and upper-middle to high-income countries (24
(Japan) to 380 per 100 000 (Brazil). The total combined prevalence of survivors
of poliomyelitis for those studies at low to moderate risk of bias ranged from
165 (high-income countries) to 425 (low-income to lower middle-income countries)
per 100 000 person-years. Historical lameness surveys of children predominated,
with wide variation in case definition and assessment criteria, and limited
relevance to current prevalence given the lack of incidence of poliovirus
infection in the ensuing years. CONCLUSIONS: These results highlight the need for
future epidemiological studies of poliomyelitis to examine nationally
representative samples, including all ages and greater focus on high-income
countries. Such efforts will improve capacity to provide reliable and more robust
worldwide prevalence estimates.
PMID- 28694347
TI - Menstrual hygiene management among Bangladeshi adolescent schoolgirls and risk
factors affecting school absence: results from a cross-sectional survey.
AB - BACKGROUND: Many adolescent girls in low-income and middle-income countries lack
appropriate facilities and support in school to manage menstruation. Little
research has been conducted on how menstruation affects school absence. This
study examines the association of menstrual hygiene management knowledge,
facilities and practice with absence from school during menstruation among
Bangladeshi schoolgirls. METHODS: We conducted a nationally representative, cross
sectional study in Bangladeshi schools from March to June 2013 among girls 11 to
17 years old who reached menarche. We sampled 700 schools from 50 urban and 50
rural clusters using a probability proportional to size technique. We interviewed
2332 schoolgirls and conducted spot checks in each school for menstrual hygiene
facilities. To assess factors associated with reported school absence, we
estimated adjusted prevalence difference (APD) for controlling confounders'
effect using generalised estimating equations to account for school-level
clustering. RESULTS: Among schoolgirls who reached menarche, 41% (931) reported
missing school, an average of 2.8 missed days per menstrual cycle. Students who
felt uncomfortable at school during menstruation (99% vs 32%; APD=58%; CI 54 to
63) and who believed menstrual problems interfere with school performance (64% vs
30%; APD=27; CI 20 to 33) were more likely to miss school during menstruation
than those who did not. School absence during menstruation was less common among
girls attending schools with unlocked toilet for girls (35% vs 43%; APD=-5.4; CI
10 to -1.6). School absence was more common among girls who were forbidden from
any activities during menstruation (41% vs 33%; APD=9.1; CI 3.3 to 14).
CONCLUSION: Risk factors for school absence included girl's attitude,
misconceptions about menstruation, insufficient and inadequate facilities at
school, and family restriction. Enabling girls to manage menstruation at school
by providing knowledge and management methods prior to menarche, privacy and a
positive social environment around menstrual issues has the potential to benefit
students by reducing school absence.
PMID- 28694348
TI - Parental knowledge, attitudes and beliefs on fever: a cross-sectional study in
Ireland.
AB - OBJECTIVES: Fever is a common symptom of mostly benign illness in young children,
yet concerning for parents. The aim of this study was to describe parental
knowledge, attitudes and beliefs regarding fever in children aged <=5 years of
age. DESIGN: A cross-sectional study using a previously validated questionnaire.
Results were analysed using descriptive statistics and multivariable logistic
regression. SETTING: Purposively selected primary schools (n=8) in Cork, Ireland,
using a paper-based questionnaire. Data were collected from a cross-sectional
internet-based questionnaire with a convenience sample of parents via websites
and web pages (n=10) previously identified in an interview study. PARTICIPANTS:
Parents with at least one child aged <=5 years were invited to participate in the
study. MAIN OUTCOME MEASURES: Parental knowledge, attitudes and beliefs when
managing fever in children. RESULTS: One thousand one hundred and four parents
contributed to this research (121 parents from schools and 983 parents through an
online questionnaire). Almost two-thirds of parents (63.1%) identified
temperatures at which they define fever that were either below or above the
recognised definition of temperature (38 degrees C). Nearly two of every three
parents (64.6%) alternate between two fever-reducing medications when managing a
child's fever. Among parents, years of parenting experience, age, sex,
educational status or marital status did not predict being able to correctly
identify a fever, neither did they predict if the parent alternated between fever
reducing medications. CONCLUSIONS: Parental knowledge of fever and fever
management was found to be deficient which concurs with existing literature.
Parental experience and other sociodemographic factors were generally not helpful
in identifying parents with high or low levels of knowledge. Resources to help
parents when managing a febrile illness need to be introduced to help all parents
provide effective care.
PMID- 28694349
TI - The linguistic and interactional factors impacting recognition and dispatch in
emergency calls for out-of-hospital cardiac arrest: a mixed-method linguistic
analysis study protocol.
AB - INTRODUCTION: Emergency telephone calls placed by bystanders are crucial to the
recognition of out-of-hospital cardiac arrest (OHCA), fast ambulance dispatch and
initiation of early basic life support. Clear and efficient communication between
caller and call-taker is essential to this time-critical emergency, yet few
studies have investigated the impact that linguistic factors may have on the
nature of the interaction and the resulting trajectory of the call. This research
aims to provide a better understanding of communication factors impacting on the
accuracy and timeliness of ambulance dispatch. METHODS AND ANALYSIS: A dataset of
OHCA calls and their corresponding metadata will be analysed from an
interdisciplinary perspective, combining linguistic analysis and health services
research. The calls will be transcribed and coded for linguistic and
interactional variables and then used to answer a series of research questions
about the recognition of OHCA and the delivery of basic life-support instructions
to bystanders. Linguistic analysis of calls will provide a deeper understanding
of the interactional dynamics between caller and call-taker which may affect
recognition and dispatch for OHCA. Findings from this research will translate
into recommendations for modifications of the protocols for ambulance dispatch
and provide directions for further research. ETHICS AND DISSEMINATION: The study
has been approved by the Curtin University Human Research Ethics Committee
(HR128/2013) and the St John Ambulance Western Australia Research Advisory Group.
Findings will be published in peer-reviewed journals and communicated to key
audiences, including ambulance dispatch professionals.
PMID- 28694350
TI - Prevalence of metabolic syndrome, discrete or comorbid diabetes and hypertension
in sub-Saharan Africa among people living with HIV versus HIV-negative
populations: a systematic review and meta-analysis protocol.
AB - INTRODUCTION: Metabolic disorder and high blood pressure are common complications
globally, and specifically among people living with HIV (PLHIV). Diabetes,
metabolic syndrome and hypertension are major risk factors for cardiovascular
diseases and their related complications. However, the burden of metabolic
syndrome, discrete or comorbid diabetes and hypertension in PLHIV compared with
HIV-negative population has not been quantified. This review and meta-analysis
aims to compare and analyse the prevalence of these trio conditions between HIV
negative and HIV-positive populations in sub-Saharan Africa (SSA). METHODS AND
ANALYSIS: The Preferred Reporting Items for Systematic Reviews and Meta-Analysis
statement guides the methods for this study. Eligibility criteria will be
published original articles (English and French language) from SSA that present
the prevalence of metabolic syndrome, discrete and/or comorbid diabetes, and
hypertension comparisons between PLHIV and HIV-negative populations. The
following databases will be searched from January 1990 to February 2017:
PubMed/Medline, EBSCOhost, Web of Science, Google Scholar, Scopus, African Index
Medicus and Cochrane Database of Systematic Reviews. Eligibility screening and
data extraction will be conducted independently by two reviewers, and
disagreements resolved by an independent reviewer. Methodological quality and
risk of bias will be assessed for individual included studies, while meta
analysis will be used to estimate study outcomes prevalence according to
subgroups. Sensitivity analysis will also be performed to further test the
robustness of the findings. ETHICS AND DISSEMINATION: This proposed study does
not require ethical approval. The results will be published as a scientific
article in a peer-reviewed journal, and presented at conferences and to relevant
health agencies. TRIAL REGISTRATION NUMBER: PROSPERO registration number
(CRD42016045727).
PMID- 28694352
TI - Protease-activated receptor-2 promotes kidney tubular epithelial inflammation by
inhibiting autophagy via the PI3K/Akt/mTOR signalling pathway.
AB - Protease-activated receptor-2 (PAR2), which belongs to a specific class of the G
protein-coupled receptors, is central to several inflammation processes. However,
the precise molecular mechanism involved remains undefined. Autophagy has been
previously shown to affect inflammation. In the present study, we examine the
effect of PAR2 on kidney tubular epithelial autophagy and on autophagy-related
inflammation and reveal the underlying mechanism involved. Autophagic activity
and levels of autophagic marker LC3 were examined in human kidney tubular
epithelial cells with PAR2 knockdown or overexpression. We administered the
mammalian target of rapamycin (mTOR) inhibitor (rapamycin) or activator (MHY1485)
to investigate the function of the phosphoinositide 3-kinase (PI3K)/Akt/mTOR
pathway. We also used transforming growth factor-beta1 (TGF-beta1)-induced HK-2
cell inflammation models to investigate the role of PAR2-associated autophagy in
kidney tubular epithelial inflammation. PAR2 antagonist and rapamycin were
administered to mice after unilateral ureteral obstruction to detect the
correlations between PAR2, autophagy, and inflammation. Our results show that
PAR2 overexpression in HK-2 cells led to a greater reduction in autophagy via the
PI3K/Akt/mTOR pathway activation and induces autophagy-related inflammation.
Meanwhile, a knockdown of PAR2 via PAR2 RNAi transfection greatly increased
autophagy and alleviated autophagy-associated inflammation. In unilateral
ureteral obstruction (UUO) kidneys, PAR2 antagonist treatment greatly attenuated
renal inflammation and interstitial injury by enhancing autophagy. Moreover,
inhibition of mTOR, rapa, markedly increased autophagy and inhibited the UUO
induced inflammation. We conclude that PAR2 induces kidney tubular epithelial
inflammation by inhibiting autophagy via the PI3K/Akt/mTOR signalling pathway.
Our results are suggestive that PAR2 inhibition may play a role in the treatment
of diseases with increased inflammatory responses in renal systems.
PMID- 28694353
TI - A centrosomal protein FOR20 regulates microtubule assembly dynamics and plays a
role in cell migration.
AB - Here, we report that a centrosomal protein FOR20 [FOP (FGFR1 (fibroblast growth
factor receptor 1) oncogene protein)-like protein of molecular mass of 20 kDa;
also named as C16orf63, FLJ31153 or PHSECRG2] can regulate the assembly and
stability of microtubules. Both FOR20 IgG antibody and GST (glutathione S
transferase)-tagged FOR20 could precipitate tubulin from the HeLa cell extract,
indicating a possible interaction between FOR20 and tubulin. FOR20 was also
detected in goat brain tissue extract and it cycled with microtubule-associated
proteins. Furthermore, FOR20 bound to purified tubulin and inhibited the assembly
of tubulin in vitro. The overexpression of FOR20 depolymerized interphase
microtubules and the depletion of FOR20 prevented nocodazole-induced
depolymerization of microtubules in HeLa cells. In addition, the depletion of
FOR20 suppressed the dynamics of individual microtubules in live HeLa cells.
FOR20-depleted MDA-MB-231 cells displayed zigzag motion and migrated at a slower
rate than the control cells, indicating that FOR20 plays a role in directed cell
migration. The results suggested that the centrosomal protein FOR20 is a new
member of the microtubule-associated protein family and that it regulates the
assembly and dynamics of microtubules.
PMID- 28694351
TI - Phosphorylation of AMPK by upstream kinases is required for activity in mammalian
cells.
AB - AMP-activated protein kinase (AMPK) plays a major role in regulating metabolism
and has attracted significant attention as a therapeutic target for treating
metabolic disorders. AMPK activity is stimulated more than 100-fold by
phosphorylation of threonine 172 (Thr172). Binding of AMP to the gamma subunit
allosterically activates the kinase. Additionally, many small molecules, e.g.
991, have been identified that bind between the kinase domain and the
carbohydrate-binding module of the beta subunit, stabilising their interaction
and leading to activation. It was reported recently that non-phosphorylated
Thr172 AMPK is activated by AMP and A769662. We present here the crystal
structure of non-phosphorylated Thr172 AMPK in complex with AMP and 991. This
structure reveals that the activation loop, as well as the complex overall, is
similar to the Thr172 phosphorylated complex. We find that in the presence of AMP
and 991 non-phosphorylated Thr172, AMPK is much less active than the Thr172
phosphorylated enzyme. In human cells, the basal level of Thr172 phosphorylation
is very low (~1%), but is increased 10-fold by treatment with 2-deoxyglucose. In
cells lacking the major Thr172 kinases, LKB1 and CaMKKbeta, Thr172
phosphorylation is almost completely abolished, and AMPK activity is virtually
undetectable. Our data show that AMP and 991 binding to non-phosphorylated Thr172
AMPK can induce an ordered, active-like, conformation of the activation loop
explaining how AMPK activity can be measured in vitro without Thr172
phosphorylation. However, in a cellular context, phosphorylation of Thr172 is
critical for significant activation of AMPK.
PMID- 28694354
TI - Myocardial Upregulation of Cathepsin D by Ischemic Heart Disease Promotes
Autophagic Flux and Protects Against Cardiac Remodeling and Heart Failure.
AB - BACKGROUND: Lysosomal dysfunction is implicated in human heart failure for which
ischemic heart disease is the leading cause. Altered myocardial expression of
CTSD (cathepsin D), a major lysosomal protease, was observed in human heart
failure, but its pathophysiological significance has not been determined. METHODS
AND RESULTS: Western blot analyses revealed an increase in the precursor but not
the mature form of CTSD in myocardial samples from explanted human failing hearts
with ischemic heart disease, which is recapitulated in chronic myocardial
infarction produced via coronary artery ligation in Ctsd+/+ but not Ctsd+/- mice.
Mice deficient of Ctsd displayed impaired myocardial autophagosome removal,
reduced autophagic flux, and restrictive cardiomyopathy. After induction of
myocardial infarction, weekly serial echocardiography detected earlier occurrence
of left ventricle chamber dilatation, greater decreases in ejection fraction and
fractional shortening, and lesser wall thickening throughout the first 4 weeks;
pressure-volume relationship analyses at 4 weeks revealed greater decreases in
systolic and diastolic functions, stroke work, stroke volume, and cardiac output;
greater increases in the ventricular weight to body weight and the lung weight to
body weight ratios and larger scar size were also detected in Ctsd+/- mice
compared with Ctsd+/+ mice. Significant increases of myocardial autophagic flux
detected at 1 and 4 weeks after induction of myocardial infarction in the Ctsd+/+
mice were diminished in the Ctsd+/- mice. CONCLUSIONS: Myocardial CTSD
upregulation induced by myocardial infarction protects against cardiac remodeling
and malfunction, which is at least in part through promoting myocardial
autophagic flux.
PMID- 28694355
TI - Peripheral Venous Pressure Measurements in Patients With Acute Decompensated
Heart Failure (PVP-HF).
AB - BACKGROUND: Accurate assessment of volume status is essential in diagnosis and
guidance of decongestive therapy in patients with acute heart failure. We sought
to compare peripheral venous pressure (PVP) with central venous pressure (CVP),
as well as other invasive hemodynamic measurements, in patients hospitalized with
an acute heart failure syndrome. METHODS AND RESULTS: PVP-HF (Peripheral Venous
Pressure Measurements in Patients With Acute Decompensated Heart Failure) was a
single-center prospective study, which enrolled patients admitted with acute
heart failure, regardless of ejection fraction or disease pathogenesis. PVP and
intracardiac pressures were obtained by transducing a peripheral intravenous and
pulmonary artery catheter, respectively, after zeroing at the phlebostatic axis.
Data were compared using Pearson's correlation coefficient and Bland-Altman
plots. A total of 30 patients (median age 64 years, 73% male, 30% ischemic
pathogenesis) were enrolled. Mean ejection fraction was 31%, and 60% had moderate
or greater right ventricular dysfunction. Median PVP was 9.5 (6-17) mm Hg, CVP
was 8.5 (6-18) mm Hg, and pulmonary capillary wedge pressure was 18 (14-21) mm
Hg. PVP and CVP were found to be highly correlated (r=0.947), while PVP and
pulmonary capillary wedge pressure were found to be moderately correlated
(r=0.565). The mean difference between PVP and CVP was 0.4 mm Hg and between PVP
and pulmonary capillary wedge pressure was 7.5 mm Hg. CONCLUSIONS: In patients
with acute heart failure syndromes, a simple assessment of PVP demonstrates a
high correlation with CVP. These findings suggest that PVP may be useful in the
standard bedside clinical assessment of volume status in these patients to help
guide decongestive therapy.
PMID- 28694356
TI - Atrial Septostomy to Treat Stiff Left Atrium Syndrome.
PMID- 28694357
TI - Floating Clots in the Descending Aorta: A Rare Complication of Femoral
Venoarterial Extracorporeal Membrane Oxygenation Combined With Microaxial Pump
for Cardiogenic Shock.
PMID- 28694358
TI - Health Care Reform In The Senate's Hands.
AB - Senate GOP hopes to act on health reform before July 4th were dashed. Meanwhile,
a leaked rule would offer broad protections for employers objecting to
contraceptive coverage.
PMID- 28694365
TI - UK hen harrier population suffers decline.
PMID- 28694360
TI - UK pet owners warned over cheap jerky treats from China.
PMID- 28694367
TI - RVC calls for cat, dog and horse blood donors.
PMID- 28694368
TI - Ectrodactyly in Limousin calves.
PMID- 28694369
TI - Human-directed aggression: are we barking up the wrong tree?
PMID- 28694373
TI - A new era of UK leadership in farm animal welfare.
PMID- 28694374
TI - Looking to India's workforce following Brexit.
PMID- 28694375
TI - Moving on from antibiotic foot baths for the control of digital dermatitis.
PMID- 28694376
TI - Price of monoclonal antibody Cytopoint.
PMID- 28694378
TI - Join the Animal Health Information Specialists.
PMID- 28694377
TI - Holly leaf ingestion causing pharyngeal obstruction in lambs.
PMID- 28694385
TI - Monocyte-derived alveolar macrophages drive lung fibrosis and persist in the lung
over the life span.
AB - Little is known about the relative importance of monocyte and tissue-resident
macrophages in the development of lung fibrosis. We show that specific genetic
deletion of monocyte-derived alveolar macrophages after their recruitment to the
lung ameliorated lung fibrosis, whereas tissue-resident alveolar macrophages did
not contribute to fibrosis. Using transcriptomic profiling of flow-sorted cells,
we found that monocyte to alveolar macrophage differentiation unfolds
continuously over the course of fibrosis and its resolution. During the fibrotic
phase, monocyte-derived alveolar macrophages differ significantly from tissue
resident alveolar macrophages in their expression of profibrotic genes. A
population of monocyte-derived alveolar macrophages persisted in the lung for one
year after the resolution of fibrosis, where they became increasingly similar to
tissue-resident alveolar macrophages. Human homologues of profibrotic genes
expressed by mouse monocyte-derived alveolar macrophages during fibrosis were up
regulated in human alveolar macrophages from fibrotic compared with normal lungs.
Our findings suggest that selectively targeting alveolar macrophage
differentiation within the lung may ameliorate fibrosis without the adverse
consequences associated with global monocyte or tissue-resident alveolar
macrophage depletion.
PMID- 28694386
TI - A type 2 cytokine axis for thymus emigration.
AB - In the thymus, stromal microenvironments support a developmental program that
generates mature T cells ready for thymic exit. The cellular and molecular
specialization within thymic stromal cells that enables their regulation of
specific stages of thymocyte development is poorly understood. Here, we show the
thymic microenvironment expresses the type 2 IL-4R complex and is functionally
responsive to its known ligands, IL-4 and IL-13. Absence of IL-4Ralpha limits
thymocyte emigration, leading to an intrathymic accumulation of mature thymocytes
within medullary perivascular spaces and reduced numbers of recent thymic
emigrants. Thymus transplantation shows this requirement maps to IL-4Ralpha
expression by stromal cells, and we provide evidence that it regulates thymic
exit via a process distinct from S1P-mediated migration. Finally, we reveal a
cellular mechanism by which IL-4+IL-13+ invariant NKT cells are necessary for IL
4Ralpha signaling that regulates thymic exit. Collectively, we define a new axis
for thymic emigration involving stimulation of the thymic microenvironment via
type 2 cytokines from innate T cells.
PMID- 28694387
TI - Inhibition of autophagy limits vertical transmission of Zika virus in pregnant
mice.
AB - Zika virus (ZIKV) infection during pregnancy leads to devastating fetal outcomes,
including intrauterine growth restriction and microcephaly. Greater understanding
of mechanisms underlying ZIKV maternal-fetal transmission is needed to develop
new therapeutic interventions. Here, we define an important role for the
autophagy pathway in ZIKV vertical transmission. ZIKV infection induced
autophagic activity in human trophoblasts and pharmacological inhibition limited
ZIKV infectivity. Furthermore, deficiency in an essential autophagy gene,
Atg16l1, in mice limited ZIKV vertical transmission and placental and fetal
damage and overall improved placental and fetal outcomes. This protection was due
to a placental trophoblast cell-autonomous effect of autophagic activity, not to
alterations in systemic maternal ZIKV infection. Finally, an autophagy inhibitor,
hydroxychloroquine, approved for use in pregnant women, attenuated placental and
fetal ZIKV infection and ameliorated adverse placental and fetal outcomes. Our
study reveals new insights into the mechanism of ZIKV vertical transmission and
suggests that an autophagy-based therapeutic warrants possible evaluation in
humans to diminish the risks of ZIKV maternal-fetal transmission.
PMID- 28694388
TI - Annexin A2 supports pulmonary microvascular integrity by linking vascular
endothelial cadherin and protein tyrosine phosphatases.
AB - Relative or absolute hypoxia activates signaling pathways that alter gene
expression and stabilize the pulmonary microvasculature. Alveolar hypoxia occurs
in disorders ranging from altitude sickness to airway obstruction, apnea, and
atelectasis. Here, we report that the phospholipid-binding protein, annexin A2
(ANXA2) functions to maintain vascular integrity in the face of alveolar hypoxia.
We demonstrate that microvascular endothelial cells (ECs) from Anxa2-/- mice
display reduced barrier function and excessive Src-related tyrosine
phosphorylation of the adherens junction protein vascular endothelial cadherin
(VEC). Moreover, unlike Anxa2+/+ controls, Anxa2-/- mice develop pulmonary edema
and neutrophil infiltration in the lung parenchyma in response to subacute
alveolar hypoxia. Mice deficient in the ANXA2-binding partner, S100A10, failed to
demonstrate hypoxia-induced pulmonary edema under the same conditions. Further
analyses reveal that ANXA2 forms a complex with VEC and its phosphatases, EC
specific protein tyrosine phosphatase (VE-PTP) and Src homology phosphatase 2
(SHP2), both of which are implicated in vascular integrity. In the absence of
ANXA2, VEC is hyperphosphorylated at tyrosine 731 in response to vascular
endothelial growth factor, which likely contributes to hypoxia-induced
extravasation of fluid and leukocytes. We conclude that ANXA2 contributes to
pulmonary microvascular integrity by enabling VEC-related phosphatase activity,
thereby preventing vascular leak during alveolar hypoxia.
PMID- 28694389
TI - Are lower TSH cutoffs in neonatal screening for congenital hypothyroidism
warranted?
AB - When newborn screening (NBS) for congenital hypothyroidism (CH) using thyroid
stimulating hormone (TSH) as a primary screening test was introduced, typical TSH
screening cutoffs were 20-50 U/L of whole blood. Over the years, lowering of TSH
cutoffs has contributed to an increased prevalence of detected CH. However, a
consensus on the benefit deriving from lowering TSH cutoffs at screening is
lacking. The present paper outlines arguments both for and against the lowering
of TSH cutoffs at NBS. It includes a review of recently published evidence from
Australia, Belgium and Italy. A section focused on economic implications of
lowering TSH cutoffs is also provided. One issue that bears further examination
is the extent to which mild iodine deficiency at the population level might
affect the association of neonatal TSH values with cognitive and developmental
outcomes. A debate on TSH cutoffs provides the opportunity to reflect on how to
make NBS for CH more effective and to guarantee optimum neurocognitive
development and a good quality of life to babies with mild as well as with severe
CH. All authors of this debate article agree on the need to establish optimal TSH
cutoffs for screening programs in various settings and to ensure the benefits of
screening and access to care for newborns worldwide.
PMID- 28694390
TI - In vitro susceptibility of geographically and temporally distinct Zika viruses to
favipiravir and ribavirin.
AB - BACKGROUND: Zika virus, a previously neglected mosquito-borne virus, is prompting
worldwide concern because of its connection with congenital defects, Guillain
Barre syndrome, meningoencephalitis and myelitis in infected individuals.
However, no specific antiviral therapy is available at present. In this study, we
investigated the in vitro susceptibility of geographically and temporally
distinct Zika viruses against the RNA polymerase inhibitors, favipiravir (T-705)
and ribavirin. METHODS: The in vitro activity of each drug and a 1:1 mixture
combination was assessed against five geographically and temporally distinct Zika
strains by plaque reduction assay (PRA), the gold standard phenotypic method.
RESULTS: We showed that both drugs exhibit in vitro inhibitory activity against
five different Zika strains isolated in different years and continents, with mean
50% inhibitory concentration (IC50) values of 35 +/-14 and 35 +/-20 uM,
respectively, by PRA. We did not observe a synergistic effect when both drugs
were combined at the equimolar concentration (IC50 =33 +/-11 uM). CONCLUSIONS:
These results indicate that T-705 has the potential to be used in patients with
complicated diseases and/or those individuals presenting with significant
comorbidities.
PMID- 28694391
TI - Transparent 1T-MoS2 nanofilm robustly anchored on substrate by layer-by-layer
self-assembly and its ultra-high cycling stability as supercapacitors.
AB - Two-dimensional MoS2 materials have attracted more and more interest and been
applied to the field of energy storage because of its unique physical, optical,
electronic and electrochemical properties. However, there are no reports on high
stable transparent MoS2 nanofilms as supercapacitors electrode. Here, we describe
a transparent 1T-MoS2 nanofilm electrode with super-long stability anchored on
the indium tin oxide (ITO) glass by a simple alternate layer-by-layer (LBL) self
assembly of a highly charged cationic poly(diallyldimethylammonium chloride)
(PDDA) and negative single-/few-layer 1T MoS2 nanosheets. The ITO/(PDDA/MoS2)20
electrode shows a transmittance of 51.6% at 550 nm and obviously exhibits
excellent transparency by naked eye observation. Ultrasonic damage test validates
that the (PDDA/MoS2)20 film with the average thickness about 50 nm is robustly
anchored on ITO substrate. Additionally, the electrochemical results indicate
that the ITO/(PDDA/MoS2)20 film shows areal capacitance of 1.1 mF cm-2 and
volumetric capacitance of 220 F cm-3 at 0.04 mA cm-2, 130.6% retention of the
original capacitance value after 5000 cycles. Further experiments indicate that
the formation of transparent (PDDA/MoS2) x nanofilm by LBL self-assembly can be
extended to other substrates, e.g., slide glass and flexible polyethylene
terephthalate (PET). Thus, the easily available (PDDA/MoS2) x nanofilm electrode
has great potential for application in transparent and/or flexible optoelectronic
and electronics devices.
PMID- 28694392
TI - Female and urban participants demonstrate an adverse trend in overall mortality
in Turkey - and a report on the TARF survey 2016.
AB - OBJECTIVE: This study is an examination of 1) overall mortality trend in the
Turkish Adult Risk Factor (TARF) study stratified by sex and place of residence,
and 2) brief report on main aspects of the 2016 survey. METHODS: The period of
last 18 years was divided into 2 for trend analysis of data. Required information
on deaths was obtained. Baseline age >=40 years at the beginning of each period
was the inclusion criterion. Cox regression analyses were performed. RESULTS:
Among over 2500 participants in each, deaths were recorded in 281 and 334
individuals in Periods 1 and 2, respectively, and baseline mean age was 54.6
years and 56.4 years, respectively, in each period. Age-adjusted hazard ratio for
mortality in Period 2 remained virtually the same for rural males, rose to
borderline significance for urban males and rural females (p=0.06, p=0.09), and
increased 1.72-fold for urban females (p=0.006), as compared to Period 1. Whereas
males gained an average of 3.8 years of survival in the later period compared
with the earlier period, females gained only 1.8 years. This narrowed the
difference in mean age at death in favor of women from 2.5 years to 0.5 year. Of
1144 participants to be surveyed in the TARF 2016, 48 were lost to follow-up, 695
were examined, and 39 participants were ascertained to be deceased. In 362 cases,
verbal information was obtained regarding health status. CONCLUSION: Gain in
survival in Turkish women has distinctly stagnated compared with men, and hazard
of death has risen significantly for women and urban residents in the past
decade, suggesting interaction between female sex and urban residence. Both
phenomena require recognition and adoption of appropriate measures.
PMID- 28694393
TI - Turkish assessment of SURF (SUrvey of Risk Factor Management) study: Control
rates of cardiovascular risk factors derived from databases of 15 different
levels of health centers in Turkey.
AB - OBJECTIVE: The aim of this study was to evaluate the adherence to recommendations
for secondary prevention and the achievement of treatment targets for the control
of risk factors in patients with established coronary heart disease (CHD) who
were followed-up at various healthcare facilities in Turkey. METHODS: According
to the protocol of the international Survey of Risk Factor Management study,
questionnaire forms were completed and demographic, anthropometric, and
laboratory data of CHD patients who were followed-up at a total of 15 selected
primary, secondary, and tertiary healthcare centers were recorded. RESULTS: Among
a total of 724 CHD patients (69.8% male; mean age: 63.3+/-10.7 years) included in
the study, 18.4% were current smokers, only 19.1% had normal body mass index, and
22.1% had waist circumference below the limit of abdominal obesity. Physical
activity was insufficient in 53% of the patients, 47.3% had low high-density
lipoprotein cholesterol value, 46% had triglyceride level above 150 mg/dL, and
67% had glycated hemoglobin value of 6.5% or above. Of all the patients, 88.1%
were using antiplatelet drugs, 71.4% were using beta-blockers, 55.7% were using
statins, and 41.9% were using angiotensin-converting enzyme
inhibitors/angiotensin receptor blockers. Blood pressure was under control in
56.7% of the hypertensive patients using antihypertensive drugs, and the
proportion of diabetic patients who reached glycemic control targets using
antidiabetic drugs was 35.9%. Low-density lipoprotein cholesterol was below 70
mg/dL in 12.2% of the patients using statins. CONCLUSION: According to the data
obtained, among Turkish CHD patients, the control rate of cardiovascular risk
factors is low, and implementation of the recommendations regarding lifestyle
modification and medication use for secondary prevention in the current
guidelines are insufficient.
PMID- 28694394
TI - Assessment of electrocardiographic parameters in adult patients undergoing
extracorporeal shockwave lithotripsy.
AB - OBJECTIVE: Extracorporeal shock wave lithotripsy (ESWL) is a safe and effective
treatment for urinary tract calculi. While serious side effects are rare,
transient cardiac arrhythmias may occur. New electrocardiographic (ECG)
parameters, such as P wave dispersion (PWD), QT dispersion (QTd), T peak to T end
(Tp-e) interval, Tp-e interval/QT ratio, and Tp-e interval/corrected QT ratio
have been defined to help predict atrial and ventricular arrhythmias. However,
effect of ESWL on these ECG parameters has not been previously investigated. The
present study was an examination of the effect of ESWL on ECG parameters.
METHODS: Total of 40 consecutive patients who underwent ESWL were prospectively
enrolled in the study. Pre-procedure ECG parameters were compared with post
procedure ECG parameters. RESULTS: PWD values were significantly longer on post
procedure ECG compared with pre-procedure ECG (p=0.017). Corrected QT duration
and QTd were significantly longer on postprocedure ECG compared with pre
procedure ECG (p=0.046 and p=0.008, respectively). In addition, Tp-e interval, Tp
e interval/QT ratio, and Tp-e interval/QTc ratio were significantly longer post
procedure (p=0.035, p=0.045, and p=0.022, respectively). In univariate
correlation analysis, duration of procedure was significantly correlated with
post-procedure PWD, QTc, and QTD values. CONCLUSION: Clinical use of ECG
parameters may be helpful in monitoring of patients receiving ungated ESWL in
order to detect cardiac dysrhythmia.
PMID- 28694395
TI - Use of tolvaptan in patients hospitalized for worsening chronic heart failure
with severe hyponatremia: The initial experience at a single-center in Turkey.
AB - OBJECTIVE: The aim of the present study was to assess the efficacy and safety of
tolvaptan for severe hyponatremia (SH) in hypervolemic heart failure (HF)
patients within daily clinical practice. METHODS: We restrospectively reviewed
our database on tolvaptan as an add-on treatment in hypervolemic patients
admitted to our clinic due to deterioration of HF and having hyponatremia
resistant to standard therapy. Severe hyponatremia was defined as serum sodium
concentration <=125 mEq/L. The database included demographic, clinical,
laboratory, and echocardiographic findings on admission, and numerous outcome
measures for oral tolvaptan treatment were used to assess its efficacy and
safety. RESULTS: The study group consisted of 56 hypervolemic HF patients with
severe hyponatremia (25 female and 31 male) with mean age of 66 years. All
patients received a single dose of tolvaptan 15 mg daily for an average of 3.2
days due to severe hyponatremia. Sodium and potassium concentrations, fluid
intake, and urine volume increased (p<0.0001, p=0.037, p<0.0001, and p<0.0001,
respectively), whereas furosemide dosage, body weight, heart rate, systolic and
diastolic blood pressure, and New York Heart Association class decreased
significantly in response to tolvaptan treatment, without a rise in serum
creatinine or urea concentrations (p<0.0001, p<0.0001, p=0.001, p<0.049, p<0.009
ve p=0.001, respectively). CONCLUSION: In this retrospective, single-centered
study conducted in a small group of Turkish patients, short-term treatment with
low-dose tolvaptan added to standard therapy of hypervolemic HF patients with
severe hyponatremia was well tolerated with a low rate of major side effects and
was effective in correcting severe hyponatremia.
PMID- 28694396
TI - Assessment of subclinical left ventricular systolic function using strain imaging
in the follow-up of patients with chronic mitral regurgitation.
AB - OBJECTIVE: Determining optimal timing for surgery in asymptomatic mitral
regurgitation (MR) remains a challenge. The aim of this study was to evaluate
subclinical changes in left ventricular (LV) systolic functions using velocity
vector imaging (VVI) during follow-up of patients with chronic mitral
regurgitation (MR). METHODS: A total of 54 patients (mean age: 57.9+/-8 years;
55% male) with moderate-to-severe MR and normal LV ejection fraction (EF), and 30
healthy controls (mean age: 56+/-6.5 years; 55% male) were evaluated using
conventional echocardiography and VVI at baseline. RESULTS: At the end of 12
months, measurements of 45 MR patients were repeated. There was no significant
change in LV dimensions or EF on follow-up. LV peak systolic strain and strain
rate (SR) were decreased in patients with MR compared with controls (strain:
16.29+/-3.30 to 23.4+/-1.9; p=0.0001 and SR: 0.93+/-0.39 to 4.9+/-0.6; p=0.0001)
at baseline. Impairment was more significant on follow-up. (strain: 13.76+/-2.68
and SR: 0.27+/-0.14; p=0.0001). CONCLUSION: VVI-derived strain imaging might be
used in the assessment of subclinical LV dysfunction and its progression during
follow-up of patients with chronic MR especially in the decision of optimal
timing for surgery.
PMID- 28694397
TI - [Effect of disease severity on upper extremity muscle strength, exercise
capacity, and activities of daily living in individuals with pulmonary arterial
hypertension].
AB - OBJECTIVE: Pulmonary arterial hypertension (PAH) is a rare disease. Although
muscle strength, exercise capacity, quality of life, and activities of daily
living of patients with PAH are affected, it is not known how they are affected
by disease severity. The purpose of the present study was to investigate effects
of disease severity on upper extremity muscle strength, exercise capacity, and
performance of activities of daily living in patients with PAH. METHODS: Twenty
five patients with disease severity classified according to the New York Heart
Association (NYHA) as functional class II (n=14) or class III (n=11) were
included in the study. Upper-extremity exercise capacity and limitations in
performing activities of daily living were assessed with 6-minute pegboard and
ring test (6PBRT) and the Milliken activities of daily living scale (MAS),
respectively. Shoulder flexion, elbow extension, elbow flexion muscle strength,
and handgrip strength were measured with dynamometer. RESULTS: There were no
significant differences in age, gender, body mass index, or mean pulmonary artery
pressure between groups (p>0.05). The 6PBRT, MAS, and elbow flexion (right) and
grip strength (right and left) results were significantly lower in NYHA III group
than in NYHA II group (p=0.004, p=0.002, p=0.043, p=0.002 and p=0.003,
respectively). There was no significant difference in shoulder flexion, elbow
flexion (left), or elbow extension between groups (p>0.05). CONCLUSION: Results
suggest that upper extremity exercise capacity, elbow flexion muscle strength
(right), and handgrip strength decrease and that limitations in activities of
daily living grow as disease severity increases in patients with PAH. When
planning rehabilitation programs, disease severity should be considered and
evaluations and treatments for the upper extremities should be included.
PMID- 28694398
TI - Renal sympathetic denervation assisted treatment of electrical storm due to
polymorphic ventricular tachycardia in a patient with cathecolaminergic
polymorphic ventricular tachycardia.
AB - Electrical storm (ES) is not a rare clinical entity. Sympathetic hyperactivity
may play critical role in development and continuation of ES. Some recent reports
have demonstrated that catheter-based renal sympathetic denervation (RSD) may
reduce sympathetic activation and have a potential role in reducing arrhythmic
burden. A 46-year-old man was admitted to clinic with frequent implantable
cardioverter defibrillator shocks and ES related to catecholaminergic polymorphic
ventricular tachycardia (VT). Tachycardia was unresponsive to administration of
beta-blockers, verapamil, and flecainide. Catheter ablation failed to suppress
initial premature ventricular contractions. Based on aggravating effects of
sympathetic system in clinical tachycardia, decision was made to perform RSD.
After the procedure, sinus rhythm was achieved and no polymorphic VT was
detected. Sustained monomorphic VT with right ventricular origin was successfully
ablated via endocardial radiofrequency ablation. This new treatment modality may
be a potential alternative method for patients in whom other ablative strategies
have been unsuccessful.
PMID- 28694399
TI - Familial hypertrophic cardiomyopathy: A case with a new mutation in the MYBPC3
gene.
AB - Familial hypertrophic cardiomyopathy is a genetically heterogeneous disease with
variable clinical features that is inherited as autosomal dominant with variable
penetrance. Recent developments in genetics of hereditary cardiomyopathy have not
only enlightened many points about pathogenesis, but have also provided great
benefit to diagnostic approaches of clinicians. Heterozygous mutation of c3691
3692insTTCA in MYBPC3 gene was identified in a pediatric patient with diagnosis
of hypertrophic cardiomyopathy at clinic. Hypertrophy was observed in sister and
father of the patient in echocardiography screening, and it was subsequently
determined that they also had same mutation. This mutation has not previously
been defined and reported previously in the literature as cause of hypertrophic
cardiomyopathy.
PMID- 28694400
TI - [Co-occurrence of Carpenter syndrome and double outlet right ventricle].
AB - Carpenter syndrome (Acrocephalopolysyndactyly type 2, OMIM 201000) is a rarely
seen autosomal recessive disorder. In addition to abnormalities such as
acrocephaly, craniosynostosis, facial asymmetry, polydactyly and syndactyly,
obesity, hypogonadism, mental retardation, and corneal opacity, it may frequently
be accompanied by congenital heart diseases such as ventricular septal defect,
patent ductus arteriosus and pulmonary stenosis. Double outlet right ventricle is
a defect in which both major arteries originate in the morphological right
ventricle. To the best of our knowledge, this is the first report in the
literature of double outlet right ventricle disease in combination with Carpenter
syndrome.
PMID- 28694401
TI - Type 1 neurofibromatosis complicated by pulmonary arterial hypertension: A case
report.
AB - Neurofibromatosis type I (NF1) is a rare genetic disease caused by mutations in
the NF1 gene, which encodes the tumor suppressor neurofibromin. Precapillary
pulmonary hypertension is a severe complication of NF1, initially described in
patients with advanced parenchymal lung disease, which may complicate the course
of NF1. Presently described is a case of neurofibromatosis complicated by
pulmonary hypertension.
PMID- 28694402
TI - Renal artery occlusion in the late postoperative period managed with renal artery
stenting after endovascular abdominal aortic aneurysm repair and renal function
salvage.
AB - Endovascular aneurysm repair (EVAR) of abdominal aorta is a valuable treatment
option in selected patients with abdominal aortic aneurysm. Renal artery
occlusion is a serious complication after EVAR and may progress to permanent
renal injury requiring hemodialysis. In this report, case of unexpected renal
artery occlusion after EVAR treated with renal artery stenting in the late
postoperative period is described.
PMID- 28694403
TI - Interesting presentation of Kounis syndrome secondary to amoxicillin/ clavulanate
use: Coronary vasospasm and simultaneous appropriate implantable defibrillator
shock.
AB - Kounis syndrome (KS) is defined as concurrent acute coronary syndrome and
allergic or hypersensitivity reactions. Despite being increasingly reported, it
is still an underdiagnosed entity. Several medications are already known to
result in KS. Amoxicillin/clavulanic acid is a frequently used antibiotic, and
its use has been linked with KS. The aim of the present report was to draw
attention to rare clinical manifestation of KS following peroral
amoxicillin/clavulanate use.
PMID- 28694404
TI - [The role of -omics technology in the pathophysiology, diagnosis, and treatment
of cardiovascular diseases].
AB - Although evident improvement has occurred in the diagnosis and treatment of
cardiovascular disease (CVD), it is still the most important cause of mortality
worldwide. The majority of the CVDs are multifactorial and polygenic. Therefore,
it is logical to use genomics, proteomics, lipidomics, and metabolomics together
for diagnosis and effective treatment of CVD. "Genome" is the combination of the
words "gene" and "chromosome," and includes all protein-coding genes and
intergenic spaces (as well as intragenic regions, or introns, within genes) in an
organism. Proteins that are synthesized in a cell, tissue, or organism are all
called proteomes. Proteomics is the study of proteomes. The analysis of the
lipodome, or all lipids synthesized in the organism, as well as lipidderived
mediators, and the functions of these mediators in biological systems, is the
field of lipidomics. The metabolome is the complete set of low-molecular-weight
metabolites and molecules in a human or any living organism. Metabolomic is the
systematic analysis of small molecules and metabolites in human or animal
biological fluids. The number of biomarkers used for the purpose of evaluating
the risk of cardiovascular events is very limited and many of them are old. The
drugs that were produced 30 years ago are still used in treatment. Development of
-omics science plays an important role in the search for new biological markers
that can be used in the diagnosis of CVD and there is a growing need for
advancement of these branches of genetics. The recognition and internalization of
-omics by clinicians is a time-consuming process, but will be more important in
the near future.
PMID- 28694405
TI - Case Image: Pseudo-pericardial tamponade caused by huge mediastinal metastatic
mass.
PMID- 28694406
TI - Case Image: Unexpected cause of lead fracture: A stylet left inside the right
ventricular pacemaker lead.
PMID- 28694407
TI - Case Image: Giant aortic vegetation caused by uncommon microorganism.
PMID- 28694408
TI - Case Image: Digital necrosis secondary to brachiocephalic artery stenosis.
PMID- 28694409
TI - Predictors of neurologically favorable survival among patients with out-of
hospital cardiac arrest: A tertiary referral hospital experience.
PMID- 28694410
TI - Authors' reply.
PMID- 28694411
TI - Amoxicillin/clavulanate allergic reaction, implantable defibrillator shock, and
Kounis syndrome: Pathophysiological considerations.
PMID- 28694412
TI - Predictors of neurologically favorable survival among patients with out-of
hospital cardiac arrest: A tertiary referral hospital experience.
PMID- 28694413
TI - Authors' reply.
PMID- 28694414
TI - [Devices to Perform Laparo-Endoscopic Single Site Surgery for Urachal Remnants
without Additional Ports].
AB - The laparoscopic management of urachal remnants has gradually become a common
practice. Recently, laparoscopic single-site surgery (LESS), a minimally invasive
approach that provides excellent cosmetic results, has been adopted in several
surgical procedures for treating urachal remnants. However, when suturing the
bladder wall or peritoneal defect during LESS it may be difficult to conduct the
procedure manually, and such cases require an additional port for suturing. Our
strategy, however, employs a knot pusher to perform the suturing without the need
for an additional port. We compared and examined the perioperative parameters of
the patients with the additional port and one without it (knot-pusher group). For
the additional-port and knot-pusher groups, the average operative time, was 146.8
and 161.7 minutes respectively, pneumoperitoneal surgery time was 90.8 and 88.0
minutes, respectively, suturing time for the bladder wall was 577 and 502
seconds, respectively suturing time for peritoneal defect was 758 vs 779 seconds,
respectively, and estimated blood loss was 19 and 9.6 ml, respectively ; there
being no significant difference between the two groups. We report our knot-pusher
method because it can achieve comparable results without compromising the
surgical outcome.
PMID- 28694415
TI - [Screening of Deep Vein Thrombosis Prior to Surgery Using D-dimer Testing and
Venous Ultrasonography of Lower Extremities].
AB - Deep vein thrombus (DVT) in a patient awaiting surgery is a considerable source
of pulmonary embolisms (PEs) during the surgical period, but screening for DVTs
has not been emphasized. This retrospective study was conducted to identify
factors associated with a positive D-dimer result and DVT diagnosis in order to
evaluate the usefulness of DVT screening for patients awaiting surgery. A total
of 1,061 patients (872 males, 189 females) underwent D-dimer testing prior to
urological surgery at Tsukuba University Hospital between April 2013 and March
2016. Factors associated with a positive D-dimer result and DVT diagnosis were
determined by a univariate analysis. Among the 75 patients with a positive Ddimer
result, venousultras onography of the lower extremitieswasperformed in 69
patientsand DVT was diagnosed in 14 patients. The overall true-positive rate of D
dimer was 20. 3% (14/69), and it was significantly higher in the females
(males11.3% vsfemales50% ; p=0.0021). Age, body mass index and Ddimer value were
not associated with the true-positive D-dimer result. Among the 1,061 patients,
DVT was significantly more likely to be diagnosed in elderly patients (median age
73.5 vs 67 yrs, p=0.0087) and females(males0. 69% vsfemales4. 23% ; p=0. 0010).
Among the three patientswith an acute-phase thrombus, two postponed surgery and
required anti-thrombus therapy, and the other patient underwent the implantation
of an inferior vena cava filter in order to undergo surgery on schedule. No PE
occurred during the surgical period. These results indicate that DVT screening
for patients awaiting surgery is useful and should be considered as part of the
prevention of PEs during the surgical period.
PMID- 28694416
TI - [A Case of Epithelioid Angiomyolipoma of the Kidney with Tumor Thrombus Extending
into the Renal Vein : Case Report].
AB - A 31-year-old man was referred to our hospital for macroscopic hematuria. An
abdominal computed tomography (CT) scan showed a 36*30 mm enhancing left renal
tumor with tumor thrombus extending into the left renal vein. Therefore,we
diagnosed the tumor as a clinically classified cT3aN0M0 left renal cell
carcinoma. Retroperitoneal laparoscopic radical left nephrectomy with renal vein
thrombectomy was performed,with removal of the left kidney with the mass and
tumor thrombus en bloc. The pathological diagnosis was epithelioid angiomyolipoma
(EAML) of the left kidney. EAML is a rare tumor with malignant potential. In this
case,although no signs of recurrence or metastasis have been observed for 9
months post-operation,we recommended a careful follow-up regimen.
PMID- 28694417
TI - [A Case Report : Metastatic Carcinoma of the Collecting Ducts of Bellini in a
Hemodialysis Patient Treated with Temsirolimus].
AB - Carcinoma of the collecting ductsof Bellini isa rare histological subtype of
renal cell carcinoma and mostly has unfavorable prognosis. Radical nephrectomy is
generally chosen for the 1st line treatment but therapeutic approaches for the
metastasis/recurrence have not been established. We report a case of carcinoma of
collecting ducts of Bellini in a patient receiving hemodialysis treated with
temsirolimus. A 62- year-old man receiving hemodialysis was admitted to our
hospital with drug-resistant anemia and high-grade cyclic fever. Computed
tomography revealed the right renal tumor and multiple metastatic lung tumors.
Open radical nephrectomy wasperformed. Pathological findingswere compatible with
carcinoma of the collecting ducts of Bellini. He was given weekly temsirolimus
treatment. The disease progressed modestly but kept the stable disease (SD)
status for six months. He died of the cancer 11 months after the initial
diagnosis.
PMID- 28694418
TI - [A Case of Long Survival in Aggressively Growing Small Cell Carcinoma of the
Bladder Successfully Treated by Combined Chemotherapy of Methotrexate, Etoposide
and Cisplatin].
AB - A 74-year-old man underwent transurethral resection for a bladder tumor (TURBT).
The pathological diagnosis was urothelial carcinoma, grade 3 pT2 at least. He
desired preservation of the bladder. Thus, MEC (methotrexate 100-150 mg/body (day
1), etoposide 100 mg/m2 (day 2-4), cisplatin 20 mg/m2 (day 2-6)) chemotherapy was
administered for 2 courses. The next year, he had a relapse in the bladder, and
the pathological diagnosiswasurothelial carcinoma, grade 2 pTa and pTis. He
underwent Calmette-Guerin Bacillus (BCG) immunotherapy for 6 courses that
resulted in a complete response without recurrence for 6 years. Six months after
the latest examination, he complained of difficulty in voiding. An 8 cm tumor in
the bladder and enlargement of obturator lymph node were detected. The
pathological diagnosis by TURBT was small cell carcinoma. He rejected cystectomy,
so we applied MEC therapy again. After 2 courses of MEC therapy, the bladder
tumor and lymphadenopathy markedly shrunk in image and almost disappeared
subsequently. The patient refused further therapy, but he had been followed
without recurrence for 48 monthsafter the chemotherapy.
PMID- 28694419
TI - [A Case of Dedifferentiated Liposarcoma of the Spermatic Cord].
AB - A 63-year-old man was referred to our department because of painless hard mass in
the right inguinal region. Abdominal computed tomography (CT) showed right
spermatic cord mass measuring 25 mm in diameter. We performed right high
orchiectomy. Histopathological diagnosis was dedifferentiated liposarcoma, which
included myofibroblast components. He was alive 3 years postoperatively without
recurrence.
PMID- 28694420
TI - Effect of Organ Scandal on Corneal Donation Rate and Organ Donors at a German
University Hospital.
AB - BACKGROUND The purpose of this study was to assess the effect of an organ
transplantation scandal on the rate of corneal donations and organ donors at the
University Hospital Tubingen. MATERIAL AND METHODS Data from all hospital deaths
from January 2012 to December 2013 were analyzed retrospectively. Each deceased
patient was considered as a potential corneal donor. The corneal donor
procurement was handled by an ophthalmic resident on a full-time basis with
standard used unchanged set of procedures. Each patient who died due to cerebral
complications was considered as a potential organ donor. During the two-year
period, a German transplantation scandal occurred at the end of 2012 and received
worldwide attention. The rates of corneal donation and organ donation in 2012 and
2013 were examined and evaluated. RESULTS Among the 1685 deceased patients,
approval for corneal donation was received in 220 cases (13.1%): 124 cases
(15.0%) in 2012 and 96 cases (11.2%) in 2013. This corresponds to a decline of
23%. The leading causes of nonfulfillment of corneal donations were refusal to
donation: 401 cases (48.4%) in 2012 and 445 cases (52.0%) in 2013; and medical
contraindications: 201 cases (24.2%) in 2012 and 212 cases (24.8%) in 2013.
During the two-year period, consent for organ donation was obtained in 25 cases
(1.5%): 15 cases (1.8%) in 2012 and 10 cases (1.2%) in 2013. The number of
realized organ donors was 20 cases (1.2%): 12 cases (1.4%) in 2012 and 8 cases
(0.9%) in 2013. This corresponds to a decline of 33%. CONCLUSIONS After a
transplantation scandal, the number of realized corneal donors and realized organ
donors decreased significantly. It seems that increasing professional performance
is very important to gaining trust inside and outside the hospital and improving
corneal and organ donation rate.
PMID- 28694421
TI - Kruppel-Like Factor 4 Enhances Sensitivity of Cisplatin to Esophageal Squamous
Cell Carcinoma (ESCC) Cells.
AB - BACKGROUND The aim of this study was to elucidate the role of Kruppel-Like factor
4 (KLF4) in cisplatin resistance in esophageal squamous cell carcinoma (ESCC)
cells, which may eventually help to improve the treatment efficacy. MATERIAL AND
METHODS Human esophageal squamous cell carcinoma (ESCC) cell line CaEs-17, TE-1,
EC109, KYSE510, KYSE140, KYSE70, and KYSE30 were selected to detect their
sensitivity to cisplatin. 5-Azacytidine-2'-deoxycytidine (5'-Aza-CdR) treatment
and methylation-specific PCR (MS-PCR) were used to detect the methylation status
for KLF4. Cell viability, apoptosis, and cell cycle were measured using methyl
thiazolyl tetrazolium (MTT) assay, Annexin V affinity assay, and flow cytometry,
respectively. RESULTS The sensitivity to cisplatin was different in the seven
ESCC cell lines, with TE-1 having the lowest sensitivity and KYSE140 having the
highest sensitivity. Interestingly, the level of KLF4 was relatively low in TE-1
cells; while it was high in KYSE140 cells. These results suggested that KLF4 may
be involved in cisplatin resistance. The promoter region was mostly unmethylated
in KYSE140 cells; while it was hypermethylated in TE-1 cells. After treatment
with demethylation reagent 5-Aza-CdR, cisplatin sensitivities were significantly
increased after upregulation of KLF4, as the IC50 values were significantly
decreased in the TE-1 cell treated with 5-Aza-CdR. Furthermore, upregulation of
KLF4 induced cell apoptosis and cell cycle arrest at S phase. CONCLUSIONS KLF4
enhances the sensitivity of cisplatin to ESCC cells through apoptosis induction
and cell cycle arrest. Our data provided a novel insight to the mechanism of
cisplatin resistance; overexpression of KLF4 may be a potential therapeutic
strategy for cisplatin resistance in human ESCC.
PMID- 28694422
TI - Development of Graft-Site Candidiasis in 3 Solid Organ Transplant Recipients from
the Same Donor.
AB - BACKGROUND Graft-site candidiasis rarely develops in solid organ transplant
recipients; however, severe life-threatening complications can occur. We report
the course of 3 solid organ transplant recipients developing graft-site
candidiasis. CASE REPORT All grafts, consisting of 2 kidneys and 1 liver, were
procured from a single donor. Patient data were collected from our database.
Candida albicans was isolated from a swab taken during multiple-organ recovery.
Complications associated with candidiasis occurred in all 3 recipients with
preservation of the liver transplant. Both renal transplant recipients had
vascular complications, eventually resulting in graft nephrectomy and subsequent
return to dialysis. The patients recovered completely without residual effects of
their prior fungal infection. CONCLUSIONS Fungal infections in solid organ
transplant recipients are rare. Since the sequelae of these infections are
serious and usually pertain to more than 1 recipient at a time, antifungal
prophylaxis may be warranted in select donors.
PMID- 28694423
TI - A new energy transfer channel from carotenoids to chlorophylls in purple
bacteria.
AB - It is unclear whether there is an intermediate dark state between the S2 and S1
states of carotenoids. Previous two-dimensional electronic spectroscopy
measurements support its existence and its involvement in the energy transfer
from carotenoids to chlorophylls, but there is still considerable debate on the
origin of this dark state and how it regulates the energy transfer process. Here
we use ab initio calculations on excited-state dynamics and simulated two
dimensional electronic spectrum of carotenoids from purple bacteria to provide
evidence supporting that the dark state may be assigned to a new Ag+ state. Our
calculations also indicate that groups on the conjugation backbone of carotenoids
may substantially affect the excited-state levels and the energy transfer
process. These results contribute to a better understanding of carotenoid excited
states.Carotenoids harvest energy from light and transfer it to chlorophylls
during photosynthesis. Here, Feng et al. perform ab initio calculations on
excited-state dynamics and simulated 2D electronic spectrum of carotenoids,
supporting the existence of a new excited state in carotenoids.
PMID- 28694424
TI - A tricyclic antidepressant, amoxapine, reduces amyloid-beta generation through
multiple serotonin receptor 6-mediated targets.
AB - Alzheimer's disease (AD) is a major and devastating neurodegenerative disease,
and the amyloid-beta (Abeta) hypothesis is still the central theory for AD
pathogenesis. Meanwhile, another major mental illness, depression, is one of the
risk factors for AD. From a high-throughput screening (HTS), amoxapine, a typical
secondary amine tricyclic antidepressant (TCA), was identified to reduce Abeta
production. A follow-up investigation on antidepressants showed that most of the
TCAs harbour similar activity. Previous studies have indicated that TCAs improve
cognitive function in AD mouse models as well as in preliminary clinical data;
however, the underlying mechanism is controversial, and the effect on Abeta is
elusive. Thus, we developed a secondary screening to determine the molecular
target of amoxapine, and serotonin receptor 6 (HTR6) was identified. Knockdown of
HTR6 reduced the amoxapine's effect, while the HTR6 antagonist SB258585 mimicked
the activity of amoxapine. Further mechanistic study showed that amoxapine and
SB258585 reduced Abeta generation through multiple HTR6-mediated targets,
including beta-arrestin2 and CDK5. Taken together, our study suggests that
amoxapine, though no longer a first-line drug for the treatment of depression,
may be beneficial for AD and further structural modification of TCAs may lead to
desirable therapeutic agents to treat both AD and depression.
PMID- 28694425
TI - Insight into microtubule disassembly by kinesin-13s from the structure of Kif2C
bound to tubulin.
AB - Kinesin-13s are critical microtubule regulators which induce microtubule
disassembly in an ATP dependent manner. To clarify their mechanism, we report
here the crystal structure of a functional construct of the kinesin-13 Kif2C/MCAK
in an ATP-like state and bound to the alphabeta-tubulin heterodimer, a complex
mimicking the species that dissociates from microtubule ends during catalytic
disassembly. Our results picture how Kif2C stabilizes a curved tubulin
conformation. The Kif2C alpha4-L12-alpha5 region undergoes a remarkable 25
degrees rotation upon tubulin binding to target the alphabeta-tubulin hinge.
This movement leads the beta5a-beta5b motif to interact with the distal end of
beta-tubulin, whereas the neck and the KVD motif, two specific elements of
kinesin-13s, target the alpha-tubulin distal end. Taken together with the study
of Kif2C mutants, our data suggest that stabilization of a curved tubulin is an
important contribution to the Kif2C mechanism.Kinesin-13s are microtubule
depolymerizing enzymes. Here the authors present the crystal structure of a
DARPin fused construct comprising the short neck region and motor domain of
kinesin-13 in complex with an alphabeta-tubulin heterodimer, which shows that
kinesin-13 functions by stabilizing a curved tubulin conformation.
PMID- 28694426
TI - Surface Interactions between Gold Nanoparticles and Biochar.
AB - Engineered nanomaterials are directly applied to the agricultural soils as a part
of pesticide/fertilize formulations or sludge/manure amendments. No prior reports
are available to understand the surface interactions between gold nanoparticles
(nAu) and soil components, including the charcoal black carbon (biochar).
Retention of citrate-capped nAu on 300-700 degrees C pecan shell biochars
occurred rapidly and irreversibly even at neutral pH where retention was less
favorable. Uniform organic (primarily citrate ligands) layer on nAu was
observable by TEM, and was preserved after the retention by biochar, which
resulted in the aggregation or alignment along the edges of multisheets composing
biochar. Retention of nAu was (i) greater on biochars than a sandy loam soil,
(ii) greater at higher ionic strength and lower pH, and (iii) pyrolysis
temperature-dependent: 500 < 700 ? 300 degrees C at pH 3. Collectively, carboxyl
enriched 300 degrees C biochar likely formed strong hydrogen bonds with the
citrate layer of nAu. The charge transfer between the conduction band of nAu and
pi* continuum of polyaromatic sheets is likely to dominate on 700 degrees C
biochar. Surface area-normalized retention of nAu on biochars was several orders
of magnitude higher than negatively charged hydroxyl-bearing environmental
surfaces, indicating the importance of black carbon in the environmental fate of
engineered nanomaterials.
PMID- 28694427
TI - Comparative phylogenetic analyses of recombinant noroviruses based on different
protein-encoding regions show the recombination-associated evolution pattern.
AB - Noroviruses are the major cause of acute gastroenteritis worldwide, and
recombination is recognized as the important mechanism for its continuous
emergence. In this study, for the common GII.P12 and GII.3 recombinants,
phylogenetic relationships based on different proteins in three ORFs were
comparatively analyzed, focusing on the influence of intergenic recombination. By
using newly designed primers, genomes of two GII.P12/GII.3 Guangzhou recombinants
were firstly amplified. Combined with other reported sequences of GII.P12_ORF1 (n
= 20), GII.3_ORF2 (n = 131), GII.3_ORF3 (n = 36), all GII.P12 and GII.3 strains
could be divided into 6, 8, and 7 clusters based on different ORFs, which showed
an obvious recombination-associated and temporally sequential evolution pattern
(with the exception of GII.P12/GII.13 recombinants). Based on multiple
alignments, 126 informative sites were identified in three ORFs (44, 54, and 28),
and four proteins (p48, p22, VP1, and VP2) were found under positive selection.
Furthermore, by using homology modeling, predicted epitopes were mapped on the P
proteins of seven GII.3 representative strains, without one (Epi: 353-361)
specific to the GII.4 VA387 strain. In summary, via the genome analyses,
phylogenetic relationships of GII.P12 and GII.3 recombinants based on the
different proteins presented a special temporally sequential evolution process
associated with their recombinant types.
PMID- 28694428
TI - Limited role of sessile acidophiles in pyrite oxidation below redox potential of
650 mV.
AB - Pyrite oxidation by mixed mesophilic acidophiles was conducted under conditions
of controlled and non-controlled redox potential to investigate the role of
sessile microbes in pyrite oxidation. Microbes attached on pyrite surfaces by
extracellular polymeric substances (EPS), and their high coverage rate was
characterized by scanning electron microscopy (SEM), confocal laser scanning
microscopy (CLSM) and atomic force microscopy (AFM). The dissolution of pyrite
was negligible if the redox potential was controlled below 650 mV (near the rest
potential of pyrite), even though the bacteria were highly active and a high
coverage rate was observed on pyrite surfaces. However, with un-controlled redox
potential the rate of pyrite oxidation increased greatly with an increasing redox
potential. This study demonstrates that sessile microbes play a limited role in
pyrite oxidation at a redox potential below 650 mV, and highlight the importance
of solution redox potential for pyrite oxidation. This has implications for acid
mine drainage control and pyrite oxidation control in biometallurgy practice.
PMID- 28694429
TI - Epidermal growth factor receptor intron-1 CA repeat polymorphism on protein
expression and clinical outcome in Taiwanese oral squamous cell carcinoma.
AB - This study was designed to explore the relationship between epidermal growth
factor receptor (EGFR) CA repeats polymorphism and protein expression in oral
cavity squamous cell carcinoma (OSCC). A total of 194 OSCCs were examined for
EGFR protein overexpression, gene copy number and the length of their CA repeats.
The length of the EGFR CA repeats was found not to be associated with EGFR gene
copy number or with protein overexpression. To exclude the effect of EGFR gene
copy number on protein overexpression, only those OSCC tumors with disomy of the
EGFR gene were included in further analysis. In this subgroup, EGFR protein
overexpression was significantly associated with poor differentiation of the
tumor cells and lymph node metastasis, especially extra-capsular spread. However,
EGFR CA repeats were not related to any clinicopathological factor.
Interestingly, patients genetically found to have the EGFR CA repeats SS genotype
and having tumors with EGFR protein overexpression were found to have a worst
prognosis in terms of disease-free survival (DFS) (HR = 2.68; 95% CI, 1.03-6.98)
after multivariate adjustment. The present study demonstrates that concurrent
overexpression of EGFR protein in the presence genetically of the SS form CA
repeats acts as a predictor for poor DFS.
PMID- 28694430
TI - Map3k8 controls granulocyte colony-stimulating factor production and neutrophil
precursor proliferation in lipopolysaccharide-induced emergency granulopoiesis.
AB - Map3k8 has been proposed as a useful target for the treatment of inflammatory
diseases. We show here that during lipopolysaccharide-induced emergency
granulopoiesis, Map3k8 deficiency strongly impairs the increase in circulating
mature (Ly6GhighCD11b+) and immature (Ly6GlowCD11b+) neutrophils. After chimaeric
bone marrow (BM) transplantation into recipient Map3k8-/- mice,
lipopolysaccharide treatment did not increase circulating Ly6GhighCD11b+ cells
and strongly decreased circulating Ly6GlowCD11b+ cells. Lipopolysaccharide
treated Map3k8-/- mice showed decreased production of granulocyte colony
stimulating factor (G-CSF), a key factor in neutrophil expansion, and a Map3k8
inhibitor blocked lipopolysaccharide-mediated G-CSF expression in endothelial
cell lines. Ly6GlowCD11b+ BM cells from lipopolysaccharide-treated Map3k8-/- mice
displayed impaired expression of CCAAT-enhancer-binding protein beta, which
depends on G-CSF for expression and is crucial for cell cycle acceleration in
this life-threatening condition. Accordingly, lipopolysaccharide-treated Map3k8-/
mice showed decreased Ly6GlowCD11b+ BM cell proliferation, as evidenced by a
decrease in the percentage of the most immature precursors, which have the
highest proliferation capacity among this cell population. Thus, Map3k8
expression by non-haematopoietic tissue is required for lipopolysaccharide
induced emergency granulopoiesis. The novel observation that inhibition of Map3k8
activity decreases neutrophilia during life-threatening systemic infection
suggests a possible risk in the proposed use of Map3k8 blockade as an anti
inflammatory therapy.
PMID- 28694431
TI - Key Role for the Organic Anion Transporters, OAT1 and OAT3, in the in vivo
Handling of Uremic Toxins and Solutes.
AB - In vitro data indicates that the kidney proximal tubule (PT) transporters of
uremic toxins and solutes (e.g., indoxyl sulfate, p-cresol sulfate, kynurenine,
creatinine, urate) include two "drug" transporters of the organic anion
transporter (OAT) family: OAT1 (SLC22A6, originally NKT) and OAT3 (SLC22A8).
Here, we have examined new and prior metabolomics data from the Oat1KO and
Oat3KO, as well as newly obtained metabolomics data from a "chemical double"
knockout (Oat3KO plus probenecid). This gives a picture of the in vivo roles of
OAT1 and OAT3 in the regulation of the uremic solutes and supports the centrality
of these "drug" transporters in independently and synergistically regulating
uremic metabolism. We demonstrate a key in vivo role for OAT1 and/or OAT3 in the
handling of over 35 uremic toxins and solutes, including those derived from the
gut microbiome (e.g., CMPF, phenylsulfate, indole-3-acetic acid). Although it is
not clear whether trimethylamine-N-oxide (TMAO) is directly transported, the
Oat3KO had elevated plasma levels of TMAO, which is associated with
cardiovascular morbidity in chronic kidney disease (CKD). As described in the
Remote Sensing and Signaling (RSS) Hypothesis, many of these molecules are
involved in interorgan and interorganismal communication, suggesting that uremia
is, at least in part, a disorder of RSS.
PMID- 28694432
TI - Seasonal variation modulates coral sensibility to heat-stress and explains annual
changes in coral productivity.
AB - The potential effects of seasonal acclimatization on coral sensitivity to heat
stress, has received limited attention despite differing bleaching thresholds for
summer and winter. In this study, we examined the response of two contrasting
phenotypes, termed winter and summer, of four Caribbean reef corals to similar
light and heat-stress levels. The four species investigated were categorized into
two groups: species with the ability to harbour large number of symbionts,
Orbicella annularis and O. faveolata, and species with reduced symbiont density
(Montastraea cavernosa and Pseudodiploria strigosa). The first group showed
higher capacity to enhance photosynthetic rates per area (Pmax), while Pmax
enhancement in the second group was more dependent on Symbiodinium performance
(Psym). In summer all four species presented higher productivity, but also higher
sensitivity to lose coral photosynthesis under heat-stress. In contrast, corals
in winter exhibit symbionts with higher capacity to photoacclimate to the
increased levels of light-stress elicited by heat-stress. Overall, our study
supports the importance of the acclimatory coral condition in addition to the
previous thermal history, to determine the severity of the impact of heat-stress
on coral physiology, but also the dependence of this response on the particular
structural and functional traits of the species.
PMID- 28694433
TI - Antidepressant effect of taurine in chronic unpredictable mild stress-induced
depressive rats.
AB - Depression, a psychiatric and dysthymic disorder, severely affects the learning,
work and life quality. The main pathogenesis of depression is associated with
central nervous system (CNS) dysfunction. Taurine has been demonstrated to exert
protective effects on the brain development and can improve learning ability and
memory. Our study investigated the antidepressant-like effects of taurine pre
treatment by examining the changes in depression-like behavior, hormones,
neurotransmitters, inflammatory factors and neurotrophic factors in the
hippocampus of a chronic unpredictable mild stress (CUMS)-induced depressive rat
model. Taurine was found to inhibit the decrease of sucrose consumption and
prevent the deficiency of spatial memory and anxiety in rats exposed to CUMS,
suggesting a preventive effect of taurine on depression-like behavior.
Furthermore, the decreased levels of 5-hydroxytryptamine, dopamine,
noradrenaline; the increased levels of glutamate, corticosterone; and the
decreased expressions of fibroblast growth factor-2, vascular endothelial growth
factor and brain derived neurotrophic factor in depressive rats were hindered by
taurine pre-administration. However, tumor necrosis factor-alpha and interleukin
1beta levels were not significantly changed by taurine. The results demonstrated
that the anti-depressive effect of taurine may be involved in the regulation of
hypothalamic-pituitary-adrenal (HPA) axis and the promotion of neurogenesis,
neuronal survival and growth in the hippocampus.
PMID- 28694434
TI - Laquinimod treatment in the R6/2 mouse model.
AB - The transgenic mouse model R6/2 exhibits Huntington's disease (HD)-like deficits
and basic pathophysiological similarities. We also used the pheochromocytoma-12
(PC12)-cell-line-model to investigate the effect of laquinimod on metabolic
activity. Laquinimod is an orally administered immunomodulatory substance
currently under development for the treatment of multiple sclerosis (MS) and HD.
As an essential effect, increased levels of BDNF were observed. Therefore, we
investigated the therapeutic efficacy of laquinimod in the R6/2 model, focusing
on its neuroprotective capacity. Weight course and survival were not influenced
by laquinimod. Neither were any metabolic effects seen in an inducible PC12-cell
line model of HD. As a positive effect, motor functions of R6/2 mice at the age
of 12 weeks significantly improved. Preservation of morphologically intact
neurons was found after treatment in the striatum, as revealed by NeuN, DARPP-32,
and ubiquitin. Biochemical analysis showed a significant increase in the brain
derived neurotrophic factor (BDNF) level in striatal but not in cortical neurons.
The number of mutant huntingtin (mhtt) and inducible nitric oxide synthase (iNOS)
positive cells was reduced in both the striatum and motor cortex following
treatment. These findings suggest that laquinimod could provide a mild effect on
motor function and striatal histopathology, but not on survival. Besides
influences on the immune system, influence on BDNF-dependent pathways in HD are
discussed.
PMID- 28694435
TI - A Simple Analytical Model for Magnetization and Coercivity of Hard/Soft
Nanocomposite Magnets.
AB - We present a simple analytical model to estimate the magnetization (sigma s) and
intrinsic coercivity (H ci) of a hard/soft nanocomposite magnet using the mass
fraction. Previously proposed models are based on the volume fraction of the hard
phase of the composite. However, it is difficult to measure the volume of the
hard or soft phase material of a composite. We synthesized Sm2Co7/Fe-Co, MnAl/Fe
Co, MnBi/Fe-Co, and BaFe12O19/Fe-Co composites for characterization of their
sigma s and H ci. The experimental results are in good agreement with the present
model. Therefore, this analytical model can be extended to predict the maximum
energy product (BH)max of hard/soft composite.
PMID- 28694436
TI - Expression and regulation of drug transporters in vertebrate neutrophils.
AB - There remains a need to identify novel pro-resolution drugs for treatment of
inflammatory disease. To date, there are no neutrophil-specific anti-inflammatory
treatments in clinical use, perhaps due to our lack of understanding of how drugs
access this complex cell type. Here we present the first comprehensive
description and expression of both major classes of drug transporters, SLC and
ABC, in resting human blood neutrophils. Moreover, we have studied the expression
of these carriers in the tractable model system, the zebrafish (Danio rerio),
additionally examining the evolutionary relationship between drug transporters in
zebrafish and humans. We anticipate that this will be a valuable resource to the
field of inflammation biology and will be an important asset in future anti
inflammatory drug design.
PMID- 28694437
TI - Integrated behavioural and stable isotope data reveal altered diet linked to low
breeding success in urban-dwelling blue tits (Cyanistes caeruleus).
AB - Animals often show reduced reproductive success in urban compared to adjacent
natural areas. The lower availability and quality of natural food in cities is
suggested as one key limiting factor. However, only few studies have provided
conclusive support by simultaneously assessing food availability, diet and
fitness. We consolidate this evidence by taking a holistic approach, comparing
blue tits breeding in forest, suburban and urban areas. We (a) assessed arthropod
availability, (b) investigated parental provisioning behaviour, (c) inferred diet
through stable isotope analysis, and (d) measured reproductive success. At the
urban site, we found a significant reduction in caterpillar availability, the
main food source of blue tits, and consequently urban tits fed their offspring
with fewer caterpillars than forest and suburban birds. Stable isotope analysis
confirmed that diet in the urban area was fundamentally different than in the
other sites. Reproductive success was lower in both urban and suburban sites
compared to the forest site, and was positively associated with volume of
provisioned caterpillars. Our findings provide strong integrative evidence that
urban blue tit nestlings are not receiving a suitable diet, and this may be an
important limiting factor for urban populations of this and potentially many
other species.
PMID- 28694438
TI - Stress induces more serious barrier dysfunction in follicle-associated epithelium
than villus epithelium involving mast cells and protease-activated receptor-2.
AB - Psychological stress has been associated with intestinal epithelial
hyperpermeability, the basic process in various functional and organic bowel
diseases. In the present study, we aimed to clarify the differences and
underlining mechanisms in stress-induced barrier disruption in functionally and
structurally distinct epitheliums, including the villus epithelium (VE) and
follicle-associated epithelium (FAE), a specialized epithelium overlaid the domes
of Peyer's lymphoid follicles. Employing an Ussing Chamber system, the epithelial
permeability was assessed in rats following water avoidance stress (WAS) in vivo
and in mucosa tissues exposed to corticotropin-releasing factor (CRF) ex vivo.
Decreased transepithelial resistance (TER) and increased paracellular and
transcellular macromolecular permeability in colon, ileal VE and FAE had been
observed in WAS rats and in CRF-exposed mucosa. Especially, the barrier
dysfunction was more serious in the FAE. Moreover, WAS upregulated the expression
of mast cell tryptase and protease-activated receptor-2 (PAR2), which positively
correlated with epithelial conductance. Mast cell stabilizer cromolyn sodium
obviously alleviated the barrier disruption induced by WAS in vivo and CRF in
vitro. Serine protease inhibitor aprotinin and FUT-175, and selective PAR2
antagonist ENMD-1068 effectively inhibited the CRF-induced FAE hyperpermeability.
Altogether, it concluded that the FAE was more susceptible to stress, and the
mast cells and PAR2 signaling played crucial roles in this process.
PMID- 28694439
TI - Reachability and the sense of embodiment in amputees using prostheses.
AB - Amputated patients are hardly satisfied with upper limb prostheses, and tend to
favour the use of their contralateral arm to partially compensate their
disability. This may seem surprising in light of recent evidences that external
objects (rubber hand or tool) can easily be embodied, namely incorporated in the
body representation. We investigated both implicit body representations (by
evaluating the peripersonal space using a reachability judgement task) and the
quality of bodily integration of the patient's prosthesis (assessed via
questionnaires). As expected, the patients estimated that they could reach
further while wearing their prosthesis, showing an embodiment of their prosthesis
in their judgement. Yet, the real reaching space was found to be smaller with
their prosthesis than with their healthy limb, showing a large error between
reachability judgement and actual capacity. An overestimation was also found on
the healthy side (comparatively to healthy subjects) suggesting a bilateral
modification of body representation in amputated patients. Finally, a correlation
was found between the quality of integration of the prosthesis and the way the
body representation changed. This study therefore illustrates the multifaceted
nature of the phenomenon of prosthesis integration, which involves its
incorporation as a tool, but also various specific subjective aspects.
PMID- 28694440
TI - Phylogenomic analysis of MKKs and MAPKs from 16 legumes and detection of
interacting pairs in chickpea divulge MAPK signalling modules.
AB - The mitogen-activated protein kinase (MAPK)-mediated phosphorylation cascade is a
vital component of plant cellular signalling. Despite this, MAPK signalling
cascade is less characterized in crop legumes. To fill this void, we present here
a comprehensive phylogeny of MAPK kinases (MKKs) and MAPKs identified from 16
legume species belonging to genistoid (Lupinus angustifolius), dalbergioid
(Arachis spp.), phaseoloid (Glycine max, Cajanus cajan, Phaseolus vulgaris, and
Vigna spp.), and galegoid (Cicer arietinum, Lotus japonicus, Medicago truncatula,
Pisum sativum, Trifolium spp., and Vicia faba) clades. Using the genes of the
diploid crop chickpea (C. arietinum), an exhaustive interaction analysis was
performed between MKKs and MAPKs by split-ubiquitin based yeast two-hybrid (Y2H).
Twenty seven interactions of varying strengths were identified between chickpea
MKKs and MAPKs. These interactions were verified in planta by bimolecular
fluorescence complementation (BiFC). As a first report in plants, four intra
molecular interactions of weak strength were identified within chickpea MKKs.
Additionally; two TEOSINTE-BRANCHED1/CYCLOIDEA/PCF (TCP) transcription factors of
class I were identified as novel down-stream interacting partners of seven MAPKs.
We propose that this highly reliable MAPK interaction network, presented here for
chickpea, can be utilized as a reference for legumes and thus will help in
deciphering their role in legume-specific events.
PMID- 28694441
TI - The glyceraldehyde-3-phosphate dehydrogenase GapDH of Corynebacterium diphtheriae
is redox-controlled by protein S-mycothiolation under oxidative stress.
AB - Mycothiol (MSH) is the major low molecular weight (LMW) thiol in Actinomycetes
and functions in post-translational thiol-modification by protein S
mycothiolation as emerging thiol-protection and redox-regulatory mechanism. Here,
we have used shotgun-proteomics to identify 26 S-mycothiolated proteins in the
pathogen Corynebacterium diphtheriae DSM43989 under hypochlorite stress that are
involved in energy metabolism, amino acid and nucleotide biosynthesis,
antioxidant functions and translation. The glyceraldehyde-3-phosphate
dehydrogenase (GapDH) represents the most abundant S-mycothiolated protein that
was modified at its active site Cys153 in vivo. Exposure of purified GapDH to
H2O2 and NaOCl resulted in irreversible inactivation due to overoxidation of the
active site in vitro. Treatment of GapDH with H2O2 or NaOCl in the presence of
MSH resulted in S-mycothiolation and reversible GapDH inactivation in vitro which
was faster compared to the overoxidation pathway. Reactivation of S-mycothiolated
GapDH could be catalyzed by both, the Trx and the Mrx1 pathways in vitro, but
demycothiolation by Mrx1 was faster compared to Trx. In summary, we show here
that S-mycothiolation can function in redox-regulation and protection of the
GapDH active site against overoxidation in C. diphtheriae which can be reversed
by both, the Mrx1 and Trx pathways.
PMID- 28694442
TI - Potassium as a pluripotency-associated element identified through inorganic
element profiling in human pluripotent stem cells.
AB - Despite their well-known function in maintaining normal cell physiology, how
inorganic elements are relevant to cellular pluripotency and differentiation in
human pluripotent stem cells (hPSCs) has yet to be systematically explored. Using
total reflection X-ray fluorescence (TXRF) spectrometry and inductively coupled
plasma mass spectrometry (ICP-MS), we analyzed the inorganic components of human
cells with isogenic backgrounds in distinct states of cellular pluripotency. The
elemental profiles revealed that the potassium content of human cells
significantly differs when their cellular pluripotency changes. Pharmacological
treatment that alters cell membrane permeability to potassium affected the
maintenance and establishment of cellular pluripotency via multiple mechanisms in
bona fide hPSCs and reprogrammed cells. Collectively, we report that potassium is
a pluripotency-associated inorganic element in human cells and provide novel
insights into the manipulation of cellular pluripotency in hPSCs by regulating
intracellular potassium.
PMID- 28694443
TI - Quantum sensing of noises in one and two dimensional quantum walks.
AB - Quantum walk (QW) provides a versatile platform for the realization of quantum
algorithms. Due to the existence of the inevitable noises in the walk, the
different quantum algorithms accommodating to different noises are demanded.
Thus, the success of the algorithms based on the QW requires us to sense
different noises in the walk. Until now, the way to distinguish different noises
in the walk has been discussed rarely. Here, we propose an efficient way to sense
the noises in the one and two dimensional QWs. The populations of the coin in the
walk with or without decoherence are presented. By only detecting the populations
of the coin in the QW, we can determine whether there exists the decoherence in
the total QW system. Moreover, the non-Markovianity of the coin in the one and
two dimensional QWs is revealed, in which the coin is taken as an open quantum
system, and the other components of the QW system is taken as the large
environment. With the measured value of the non-Markovianity for the coin, we can
conjecture which kinds of noise emerges in the one and two dimensional QWs.
PMID- 28694444
TI - Preliminary estimates of the abundance and fidelity of dolphins associating with
a demersal trawl fishery.
AB - The incidental capture of wildlife in fishing gear presents a global conservation
challenge. As a baseline to inform assessments of the impact of bycatch on
bottlenose dolphins (Tursiops truncatus) interacting with an Australian trawl
fishery, we conducted an aerial survey to estimate dolphin abundance across the
fishery. Concurrently, we carried out boat-based dolphin photo-identification to
assess short-term fidelity to foraging around trawlers, and used photographic and
genetic data to infer longer-term fidelity to the fishery. We estimated abundance
at ~ 2,300 dolphins (95% CI = 1,247-4,214) over the ~ 25,880-km2 fishery. Mark
recapture estimates yielded 226 (SE = 38.5) dolphins associating with one trawler
and some individuals photographed up to seven times over 12 capture periods.
Moreover, photographic and genetic re-sampling over three years confirmed that
some individuals show long-term fidelity to trawler-associated foraging. Our
study presents the first abundance estimate for any Australian pelagic dolphin
community and documents individuals associating with trawlers over days, months
and years. Without trend data or correction factors for dolphin availability, the
impact of bycatch on this dolphin population's conservation status remains
unknown. These results should be taken into account by management agencies
assessing the impact of fisheries-related mortality on this protected species.
PMID- 28694445
TI - Effect of Li Termination on the Electronic and Hydrogen Storage Properties of
Linear Carbon Chains: A TAO-DFT Study.
AB - Accurate prediction of the electronic and hydrogen storage properties of linear
carbon chains (C n ) and Li-terminated linear carbon chains (Li2C n ), with n
carbon atoms (n = 5-10), has been very challenging for traditional electronic
structure methods, due to the presence of strong static correlation effects. To
meet the challenge, we study these properties using our newly developed thermally
assisted-occupation density functional theory (TAO-DFT), a very efficient
electronic structure method for the study of large systems with strong static
correlation effects. Owing to the alteration of the reactivity of C n and Li2C n
with n, odd-even oscillations in their electronic properties are found. In
contrast to C n , the binding energies of H2 molecules on Li2C n are in (or close
to) the ideal binding energy range (about 20 to 40 kJ/mol per H2). In addition,
the H2 gravimetric storage capacities of Li2C n are in the range of 10.7 to 17.9
wt%, satisfying the United States Department of Energy (USDOE) ultimate target of
7.5 wt%. On the basis of our results, Li2C n can be high-capacity hydrogen
storage materials that can uptake and release hydrogen at temperatures well above
the easily achieved temperature of liquid nitrogen.
PMID- 28694446
TI - Ticks infected via co-feeding transmission can transmit Lyme borreliosis to
vertebrate hosts.
AB - Vector-borne pathogens establish systemic infections in host tissues to maximize
transmission to arthropod vectors. Co-feeding transmission occurs when the
pathogen is transferred between infected and naive vectors that feed in close
spatiotemporal proximity on a host that has not yet developed a systemic
infection. Borrelia afzelii is a tick-borne spirochete bacterium that causes Lyme
borreliosis (LB) and is capable of co-feeding transmission. Whether ticks that
acquire LB pathogens via co-feeding are actually infectious to vertebrate hosts
has never been tested. We created nymphs that had been experimentally infected as
larvae with B. afzelii via co-feeding or systemic transmission, and compared
their performance over one complete LB life cycle. Co-feeding nymphs had a
spirochete load that was 26 times lower than systemic nymphs but both nymphs were
highly infectious to mice (i.e., probability of nymph-to-host transmission of B.
afzelii was ~100%). The mode of transmission had no effect on the other infection
phenotypes of the LB life cycle. Ticks that acquire B. afzelii via co-feeding
transmission are highly infectious to rodents, and the resulting rodent infection
is highly infectious to larval ticks. This is the first study to show that B.
afzelii can use co-feeding transmission to complete its life cycle.
PMID- 28694447
TI - Impacts of Early Life Stress on the Methylome and Transcriptome of Atlantic
Salmon.
AB - Exposure to environmental stressors during early-life stages can change the rate
and timing of various developmental processes. Epigenetic marks affecting
transcriptional regulation can be altered by such environmental stimuli. To
assess how stress might affect the methylome and transcriptome in salmon, fish
were treated using cold-shock and air-exposure from the eye-stage until start
feeding. The fish were either stressed prior to hatching (E), post-hatching (PH),
pre- and post-hatching (EPH) or not stressed (CO). Assessing transcriptional
abundances just prior to start feeding, E and PH individuals were found to have
modified the expression of thousands of genes, many with important functions in
developmental processes. The EPH individuals however, showed expression similar
to those of CO, suggesting an adaptive response to extended periods of stress.
The methylome of stressed individuals differed from that of the CO, suggesting
the importance of environment in shaping methylation signatures. Through
integration of methylation with transcription, we identified bases with potential
regulatory functions, some 10s of kb away from the targeted genes. We then
followed fish growth for an additional year. Individuals in EPH showed superior
growth compared to other treatment groups, highlighting how stress can
potentially have long-lasting effects on an organism's ability to adapt to
environmental perturbations.
PMID- 28694448
TI - Non-linear optical measurement of the twist elastic constant in thermotropic and
DNA lyotropic chiral nematics.
AB - Throughout the whole history of liquid crystals science, the balancing of
intrinsic elasticity with coupling to external forces has been the key strategy
for most application and investigation. While the coupling of the optical field
to the nematic director is at the base of a wealth of thoroughly described
optical effects, a significant variety of geometries and materials have not been
considered yet. Here we show that by adopting a simple cell geometry and
measuring the optically induced birefringence, we can readily extract the twist
elastic coefficient K22 of thermotropic and lyotropic chiral nematics (N*). The
value of K22 we obtain for chiral doped 5CB thermotropic N* well matches those
reported in the literature. With this same strategy, we could determine for the
first time K22 of the N* phase of concentrated aqueous solutions of DNA
oligomers, bypassing the limitations that so far prevented measuring the elastic
constants of this class of liquid crystalline materials. The present study also
enlightens the significant nonlinear optical response of DNA liquid crystals.
PMID- 28694449
TI - Future changes in the climatology of the Great Plains low-level jet derived from
fine resolution multi-model simulations.
AB - The southerly Great Plains low-level jet (GPLLJ) is one of the most significant
circulation features of the central U.S. linking large-scale atmospheric
circulation with the regional climate. GPLLJs transport heat and moisture,
contribute to thunderstorm and severe weather formation, provide a corridor for
the springtime migration of birds and insects, enhance wind energy availability,
and disperse air pollution. We assess future changes in GPLLJ frequency using an
eight member ensemble of dynamically-downscaled climate simulations for the mid
21st century. Nocturnal GPLLJ frequency is projected to increase in the southern
plains in spring and in the central plains in summer, whereas current
climatological patterns persist into the future for daytime and cool season
GPLLJs. The relationship between future GPLLJ frequency and the extent and
strength of anticyclonic airflow over eastern North America varies with season.
Most simulations project a westward shift of anticyclonic airflow in summer, but
uncertainty is larger for spring with only half of the simulations suggesting a
westward expansion. The choice of regional climate model and the driving lateral
boundary conditions have a large influence on the projected future changes in
GPLLJ frequency and highlight the importance of multi-model ensembles to estimate
the uncertainty surrounding the future GPLLJ climatology.
PMID- 28694450
TI - Modelling West Nile virus transmission risk in Europe: effect of temperature and
mosquito biotypes on the basic reproduction number.
AB - West Nile virus (WNV) is a mosquito-borne flavivirus which has caused repeated
outbreaks in humans in southern and central Europe, but thus far not in northern
Europe. The main mosquito vector for WNV, Culex pipiens, consists of two
behaviourally distinct biotypes, pipiens and molestus, which can form hybrids.
Differences between biotypes, such as vector competence and host preference,
could be important in determining the risk of WNV outbreaks. Risks for WNV
establishment can be modelled with basic reproduction number (R 0) models.
However, existing R 0 models have not differentiated between biotypes. The aim of
this study was, therefore, to explore the role of temperature-dependent and
biotype-specific effects on the risk of WNV establishment in Europe. We developed
an R 0 model with temperature-dependent and biotype-specific parameters, and
calculated R 0 values using the next-generation matrix for several scenarios
relevant for Europe. In addition, elasticity analysis was done to investigate the
contribution of each biotype to R 0. Global warming and increased mosquito-to
host ratios can possibly result in more intense WNV circulation in birds and
spill-over to humans in northern Europe. Different contributions of the Cx.
pipiens biotypes to R 0 shows the importance of including biotype-specific
parameters in models for reliable WNV risk assessments.
PMID- 28694451
TI - Polymorphic regulation of mitochondrial fission and fusion modifies phenotypes of
microglia in neuroinflammation.
AB - Microglia are the resident macrophages of the central nervous system and play
complex roles in the milieu of diseases including the primary diseases of myelin.
Although mitochondria are critical for cellular functions and survival in the
nervous system, alterations in and the roles of mitochondrial dynamics and
associated signaling in microglia are still poorly understood. In the present
study, by combining immunohistochemistry and 3D ultrastructural analyses, we show
that mitochondrial fission/fusion in reactive microglia is differentially
regulated from that in monocyte-derived macrophages and the ramified microglia of
normal white matter in myelin disease models. Mouse cerebral microglia in vitro
demonstrated that stimulation of TLR4 with lipopolysaccharide, widely used to
examine microglial reactions, caused the activation of the mitochondrial fission
protein, dynamin-related protein 1 (Drp1) and enhanced production of reactive
oxygen species (ROS). The increase in the ROS level activated 5' adenosine
monophosphate-activated protein kinase (AMPK), and facilitated elongation of
mitochondria along the microtubule tracks. These results suggest that the
polymorphic regulation of mitochondrial fission and fusion in reactive microglia
is mediated by distinct signaling under inflammatory conditions, and modulates
microglial phenotypes through the production of ROS.
PMID- 28694452
TI - Phosphatidylserine-mediated platelet clearance by endothelium decreases platelet
aggregates and procoagulant activity in sepsis.
AB - The mechanisms that eliminate activated platelets in inflammation-induced
disseminated intravascular coagulation (DIC) in micro-capillary circulation are
poorly understood. This study explored an alternate pathway for platelet disposal
mediated by endothelial cells (ECs) through phosphatidylserine (PS) and examined
the effect of platelet clearance on procoagulant activity (PCA) in sepsis.
Platelets in septic patients demonstrated increased levels of surface activation
markers and apoptotic vesicle formation, and also formed aggregates with
leukocytes. Activated platelets adhered were and ultimately digested by ECs in
vivo and in vitro. Blocking PS on platelets or alphavbeta3 integrin on ECs
attenuated platelet clearance resulting in increased platelet count in a mouse
model of sepsis. Furthermore, platelet removal by ECs resulted in a corresponding
decrease in platelet-leukocyte complex formation and markedly reduced generation
of factor Xa and thrombin on platelets. Pretreatment with lactadherin
significantly increased phagocytosis of platelets by approximately 2-fold,
diminished PCA by 70%, prolonged coagulation time, and attenuated fibrin
formation by 50%. Our results suggest that PS-mediated clearance of activated
platelets by the endothelium results in an anti-inflammatory, anticoagulant, and
antithrombotic effect that contribute to maintaining platelet homeostasis during
acute inflammation. These results suggest a new therapeutic target for impeding
the development of DIC.
PMID- 28694453
TI - Portable and Error-Free DNA-Based Data Storage.
AB - DNA-based data storage is an emerging nonvolatile memory technology of
potentially unprecedented density, durability, and replication efficiency. The
basic system implementation steps include synthesizing DNA strings that contain
user information and subsequently retrieving them via high-throughput sequencing
technologies. Existing architectures enable reading and writing but do not offer
random-access and error-free data recovery from low-cost, portable devices, which
is crucial for making the storage technology competitive with classical
recorders. Here we show for the first time that a portable, random-access
platform may be implemented in practice using nanopore sequencers. The novelty of
our approach is to design an integrated processing pipeline that encodes data to
avoid costly synthesis and sequencing errors, enables random access through
addressing, and leverages efficient portable sequencing via new iterative
alignment and deletion error-correcting codes. Our work represents the only known
random access DNA-based data storage system that uses error-prone nanopore
sequencers, while still producing error-free readouts with the highest reported
information rate/density. As such, it represents a crucial step towards practical
employment of DNA molecules as storage media.
PMID- 28694454
TI - Graphene Oxide Sheets Combine into Conductive Coatings by Direct Oxidative
Electropolymerization.
AB - New coatings are obtained when graphene oxide is further oxidized at moderate
anodic potentials (<=~1.3 V vs. Ag/AgCl). Based on a variety of spectroscopic and
electrochemical observations, the coatings are attributed to the direct
electropolymerization of graphene oxide sheets via oxidation of the phenol edge
groups on graphene. Depending on the applied potential, ether or carboxylic
groups are formed. The coatings obtained via further oxidation are characterized
by a lower O/C ratio due to decarboxylation and a higher content of C=C bonds.
These bonds extend aromatic conjugation into the combined graphene oxide sheets
and are responsible for the highly conductive nature of these coatings.
PMID- 28694455
TI - Asymptomatic Meibomian Gland Dysfunction and Cardiovascular Disease Risk Factors
in a Middle-Aged Population in Taiwan - A Cross-sectional Analysis.
AB - Managing cardiovascular disease (CVD) risk factors is the key to prevent CVD.
This study aimed to prevent CVD by introducing asymptomatic meibomian gland
dysfunction (MGD), a condition associated with various CVD risk factors, as an
early indicator for CVD in middle-aged population. Participants with and without
asymptomatic MGD underwent standardized questionnaires, physical examinations,
and laboratory investigations. One ophthalmologist completed the identification
and grading of MGD by using slit-lamp biomicroscopy examination on the eyelid
margins, meibomian gland orifices, and meibomian gland secretions. Standardized
techniques were used to measure the CVD risk factor parameters. After adjusted
for age and gender, CVD risk factors including elevated uric acid (P = 0.01),
total cholesterol (Total-C, P < 0.001), low-density lipoprotein cholesterol (LDL
C, P < 0.001), fasting triglyceride (Fasting TG, P < 0.001), decreased high
density lipoprotein cholesterol (HDL-C, P = 0.04), and presence of hepatic
steatosis (P = 0.008) were significantly associated with asymptomatic MGD.
Stepwise logistic regression analysis revealed that LDL-C (OR: 1.03, 95% CI: 1.02
1.04) and Fasting TG (OR: 1.01; 95% CI: 1.00-1.01) levels were risk factors for
having asymptomatic MGD (P < 0.001). Together, the results suggest that
asymptomatic MGD may serve as an indicator for CVD.
PMID- 28694456
TI - Single-cell transcriptomics of East-Asian pancreatic islets cells.
AB - Single-cell RNA-seq (scRNA-seq) of pancreatic islets have reported on alpha- and
beta-cell gene expression in mice and subjects of predominantly European
ancestry. We aimed to assess these findings in East-Asian islet-cells. 448 islet
cells were captured from three East-Asian non-diabetic subjects for scRNA-seq.
Hierarchical clustering using pancreatic cell lineage genes was used to assign
cells into cell-types. Differentially expressed transcripts between alpha- and
beta-cells were detected using ANOVA and in silico replications of mouse and
human islet cell genes were performed. We identified 118 alpha, 105 beta, 6 delta
endocrine cells and 47 exocrine cells. Besides INS and GCG, 26 genes showed
differential expression between alpha- and beta-cells. 10 genes showed concordant
expression as reported in rodents, while FAM46A was significantly discordant.
Comparing our East-Asian data with data from primarily European subjects, we
replicated several genes implicated in nuclear receptor activations, acute phase
response pathway, glutaryl-CoA/tryptophan degradations and EIF2/AMPK/mTOR
signaling. Additionally, we identified protein ubiquitination to be associated
among East-Asian beta-cells. We report on East-Asian alpha- and beta-cell gene
signatures and substantiate several genes/pathways. We identify expression
signatures in East-Asian beta-cells that perhaps reflects increased
susceptibility to cell-death and warrants future validations to fully appreciate
their role in East-Asian diabetes pathogenesis.
PMID- 28694458
TI - Gamma-ray vortices from nonlinear inverse Thomson scattering of circularly
polarized light.
AB - Inverse Thomson scattering is a well-known radiation process that produces high
energy photons both in nature and in the laboratory. Nonlinear inverse Thomson
scattering occurring inside an intense light field is a process which generates
higher harmonic photons. In this paper, we theoretically show that the higher
harmonic gamma-ray produced by nonlinear inverse Thomson scattering of circularly
polarized light is a gamma-ray vortex, which means that it possesses a helical
wave front and carries orbital angular momentum. Our work explains a recent
experimental result regarding nonlinear inverse Thomson scattering that clearly
shows an annular intensity distribution as a remarkable feature of a vortex beam.
Our work implies that gamma-ray vortices should be produced in various situations
in astrophysics in which high-energy electrons and intense circularly polarized
light fields coexist. Nonlinear inverse Thomson scattering is a promising
radiation process for realizing a gamma-ray vortex source based on currently
available laser and accelerator technologies, which would be an indispensable
tool for exploring gamma-ray vortex science.
PMID- 28694457
TI - Characterisation of preproendothelin-1 derived peptides identifies Endothelin
Like Domain Peptide as a modulator of Endothelin-1.
AB - Endothelin-1 (ET-1) is involved in the pathogenesis of cardiac and renal
diseases, and in the progression of tumour growth in cancer, but current
diagnosis and treatment remain inadequate. Peptides derived from the 212 amino
acid precursor preproendothelin-1 (ppET-1) may have utility as biomarkers, or
cause biological effects that are unaffected by endothelin receptor antagonists.
Here, we used specific immunoassays and LC-MS/MS to identify NT-proET-1 (ppET
1[18-50]), Endothelin-Like Domain Peptide (ELDP, ppET-1[93-166]) and CT-proET-1
(ppET-1[169-212]) in conditioned media from cultured endothelial cells. Synthesis
of these peptides correlated with ET-1, and plasma ELDP and CT-proET-1 were
elevated in patients with chronic heart failure. Clearance rates of NT-proET-1,
ELDP and CT-proET-1 were determined after i.v. injection in anaesthetised rats.
CT-proET-1 had the slowest systemic clearance, hence providing a biological basis
for it being a better biomarker of ET-1 synthesis. ELDP contains the evolutionary
conserved endothelin-like domain sequence, which potentially confers biological
activity. On isolated arteries ELDP lacked direct vasoconstrictor effects.
However, it enhanced ET-1 vasoconstriction and prolonged the increase in blood
pressure in anaesthetised rats. ELDP may therefore contribute to disease
pathogenesis by augmenting ET-1 responses.
PMID- 28694459
TI - Material-Device-Circuit Co-optimization of 2D Material based FETs for Ultra
Scaled Technology Nodes.
AB - Two-dimensional (2D) material based FETs are being considered for future
technology nodes and high performance logic applications. However, a
comprehensive assessment of 2D material based FETs has been lacking for high
performance logic applications considering appropriate system level figure-of
merits (FOMs) e.g. delay, and energy-delay product. In this paper, we present
guidelines for 2D material based FETs to meet sub-10 nm high performance logic
requirements focusing on material requirement, device design, energy-delay
optimization for the first time. We show the need for 2D materials with smaller
effective mass in the transport direction and anisotropicity to meet the
performance requirement for future technology nodes. We present novel device
designs with one such 2D material (monolayer black-phosphorus) to keep Moore's
alive for the HP logic in sub-5 nm gate length regime. With these device
proposals we show that below 5 nm gate lengths 2D electrostatistics arising from
gate stack design becomes more of a challenge than direct source-to-drain
tunneling for 2D material-based FETs. Therefore, it is challenging to meet both
delay and energy-delay requirement in sub-5 nm gate length regime without scaling
both supply voltage (V DD ) and effective-oxide-thickness (EOT) below 0.5 V and
0.5 nm respectively.
PMID- 28694460
TI - Two Bombyx mori acetylcholinesterase genes influence motor control and
development in different ways.
AB - Among its other biological roles, acetylcholinesterase (AChE, EC 3.1.1.7),
encoded by two ace in most insects, catalyses the breakdown of acetylcholine,
thereby terminating synaptic transmission. ace1 encodes the synaptic enzyme and
ace2 has other essential actions in many insect species, such as Chilo
suppressalis and Plutella xylostella. The silkworm, Bombyx mori, has been
domesticated for more than two thousand years and its aces have no history of
pesticide exposure. Here, we investigated the functional differences between two
ace genes, BmAce1 and BmAce2, in the silkworm. qPCR analysis indicated that
BmAce1 is highly expressed in muscle and BmAce2 is more ubiquitously expressed
among tissues and enriched in the head. Both genes were separately suppressed
using chemically synthesized siRNAs. The mRNA abundance of the two ace genes was
significantly reduced to about 13% - 75% of the control levels after siRNA
injection. The AChE activities were decreased to 32% to 85% of control levels.
Silencing BmAce2 resulted in about 26% mortality, faster and higher than the 20%
in the siBmAce1-treated group. Silencing BmAce1 impacted motor control and
development to a greater extent than silencing BmAce2, although both treatment
groups suffered motor disability, slowed development and reduced cocoons. Both
genes have essential, differing biological significance.
PMID- 28694461
TI - Endothelial Hey2 deletion reduces endothelial-to-mesenchymal transition and
mitigates radiation proctitis in mice.
AB - The current study evaluated the role of Hey2 transcription factor in radiation
induced endothelial-to-mesenchymal transition (EndoMT) and its impact on
radiation-induced tissue damage in mice. Phenotypic modifications of irradiated,
Hey2 siRNA- and Hey2 vector plasmid-transfected human umbilical vein endothelial
cells (HUVECs) resembling EndoMT were monitored by qPCR, immunocytochemistry and
western blots. Subsequently, in mice, a Cre-LoxP strategy for inactivation of
Hey2 specifically in the endothelium was used to study the biological
consequences. Total body irradiation and radiation proctitis were monitored to
investigate the impact of conditional Hey2 deletion on intestinal stem cells and
microvascular compartment radiosensitivity, EndoMT and rectal damage severity. We
found that EndoMT occurs in irradiated HUVECs with concomitant Hey2 mRNA and
protein increase. While Hey2 silencing has no effect on radiation-induced EndoMT
in vitro, Hey2 overexpression is sufficient to induce phenotypic conversion of
endothelial cells. In mice, the conditional deletion of Hey2 reduces EndoMT
frequency and the severity of rectal tissue damage. Our data indicate that the
reduction in mucosal damage occurs through decline in stem/clonogenic epithelial
cell loss mediated by microvascular protection. EndoMT is involved in radiation
proctitis and this study demonstrates that a strategy based on the reduction of
EndoMT mitigates intestinal tissue damage.
PMID- 28694462
TI - Transgenerational inheritance of susceptibility to diabetes-induced male
subfertility.
AB - Male infertility is a worldwide problem associated with genetic background,
environmental factors, and diseases. One of the suspected contributing factors to
male infertility is diabetes mellitus. We investigated the molecular and
morphological changes in sperms and testicular tissue of diabetic males. The
study was performed in streptozotocin-induced type 1 diabetes mouse model.
Diabetes decreased sperm concentration and viability and increased sperm
apoptosis. Changes in protamine 1/protamine 2 ratio indicated reduced sperm
quality. The testicular tissue of diabetic males showed significant tissue
damage, disruption of meiotic progression, and changes in the expression of genes
encoding proteins important for spermiogenesis. Paternal diabetes altered sperm
quality and expression pattern in the testes in offspring of two subsequent
generations. Our study revealed that paternal diabetes increased susceptibility
to infertility in offspring through gametic alternations. Our data also provide a
mechanistic basis for transgenerational inheritance of diabetes-associated
pathologies since protamines may be involved in epigenetic regulations.
PMID- 28694463
TI - Contrast-enhanced MR microscopy of amyloid plaques in five mouse models of
amyloidosis and in human Alzheimer's disease brains.
AB - Gadolinium (Gd)-stained MRI is based on Gd contrast agent (CA) administration
into the brain parenchyma. The strong signal increase induced by Gd CA can be
converted into resolution enhancement to record microscopic MR images. Moreover,
inhomogeneous distribution of the Gd CA in the brain improves the contrast
between different tissues and provides new contrasts in MR images. Gd-stained MRI
detects amyloid plaques, one of the microscopic lesions of Alzheimer's disease
(AD), in APPSL/PS1M146L mice or in primates. Numerous transgenic mice with
various plaque typologies have been developed to mimic cerebral amyloidosis and
comparison of plaque detection between animal models and humans with new imaging
methods is a recurrent concern. Here, we investigated detection of amyloid
plaques by Gd-stained MRI in five mouse models of amyloidosis (APPSL/PS1M146L,
APP/PS1dE9, APP23, APPSwDI, and 3xTg) presenting with compact, diffuse and
intracellular plaques as well as in post mortem human-AD brains. The brains were
then evaluated by histology to investigate the impact of size, compactness, and
iron load of amyloid plaques on their detection by MRI. We show that Gd-stained
MRI allows detection of compact amyloid plaques as small as 25 um, independently
of their iron load, in mice as well as in human-AD brains.
PMID- 28694464
TI - Monocular deprivation induces dendritic spine elimination in the developing mouse
visual cortex.
AB - It is well established that visual deprivation has a profound impact on the
responsiveness of neurons in the developing visual cortex. The effect of visual
deprivation on synaptic connectivity remains unclear. Using transcranial two
photon microscopy, we examined the effect of visual deprivation and subsequent
recovery on dendritic spine remodeling of layer 5 pyramidal neurons in the mouse
primary visual cortex. We found that monocular deprivation (MD), but not
binocular deprivation (BD), increased dendritic spine elimination over 3 days in
the binocular region of 4-week-old adolescent mice. This MD-induced dendritic
spine elimination persisted during subsequent 2-4 days of binocular recovery.
Furthermore, we found that average dendritic spine sizes were decreased and
increased following 3-day MD and BD, respectively. These spine size changes
induced by MD or BD tended to be reversed during subsequent binocular recovery.
Taken together, these findings reveal differential effects of MD and BD on
synaptic connectivity of layer 5 pyramidal neurons and underscore the persistent
impact of MD on synapse loss in the developing visual cortex.
PMID- 28694465
TI - Generation of complement protein C3 deficient pigs by CRISPR/Cas9-mediated gene
targeting.
AB - Complement protein C3 is the pivotal component of the complement system. Previous
studies have demonstrated that C3 has implications in various human diseases and
exerts profound functions under certain conditions. However, the delineation of
pathological and physiological roles of C3 has been hampered by the insufficiency
of suitable animal models. In the present study, we applied the clustered
regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated (Cas)
system to target the C3 gene in porcine fetal fibroblasts. Our results indicated
that CRISPR/Cas9 targeting efficiency was as high as 84.7%, and the biallelic
mutation efficiency reached at 45.7%. The biallelic modified colonies were used
as donor for somatic cell nuclear transfer (SCNT) technology to generate C3
targeted piglets. A total of 19 C3 knockout (KO) piglets were produced and their
plasma C3 protein was undetectable by western blot analysis and ELISA. The
hemolytic complement activity and complement-dependent cytotoxicity assay further
confirmed that C3 was disrupted in these piglets. These C3 KO pigs could be
utilized as a valuable large animal model for the elucidation of the roles of C3.
PMID- 28694466
TI - The role of directional interactions in the designability of generalized
heteropolymers.
AB - Heteropolymers are important examples of self-assembling systems. However, in the
design of artificial heteropolymers the control over the single chain self
assembling properties does not reach that of the natural bio-polymers, and in
particular proteins. Here, we introduce a sufficiency criterion to identify
polymers that can be designed to adopt a predetermined structure and show that it
is fulfilled by polymers made of monomers interacting through directional
(anisotropic) interactions. The criterion is based on the appearance of a
particular peak in the radial distribution function, that we show being a
universal feature of all designable heteropolymers, as it is present also in
natural proteins. Our criterion can be used to engineer new self-assembling
modular polymers that will open new avenues for applications in materials
science.
PMID- 28694467
TI - Synthesis of nanobelt-like 1-dimensional silver/nanocarbon hybrid materials for
flexible and wearable electroncs.
AB - Most synthetic processes of metallic nanostructures were assisted by
organic/inorganic or polymeric materials to control their shapes to one-dimension
or two-dimension. However, these additives have to be removed after synthesis of
metal nanostructures for applications. Here we report a straightforward method
for the low-temperature and additive-free synthesis of nanobelt-like silver
nanostructures templated by nanocarbon (NC) materials via bio-inspired shape
control by introducing supramolecular 2-ureido-4[1H]pyrimidinone (UPy) groups
into the NC surface. The growth of the Ag nanobelt structure was found to be
induced by these UPy groups through observation of the selective formation of Ag
nanobelts on UPy-modified carbon nanotubes and graphene surfaces. The synthesized
NC/Ag nanobelt hybrid materials were subsequently used to fabricate the highly
conductive fibres (>1000S/cm) that can function as a conformable electrode and
highly tolerant strain sensor, as well as a highly conductive and robust paper
(>10000S/cm after thermal treatment).
PMID- 28694468
TI - Interactome and reciprocal activation of pathways in topical mesenchymal stem
cells and the recipient cerebral cortex following traumatic brain injury.
AB - In this study, GFP-MSCs were topically applied to the surface of cerebral cortex
within 1 hour of experimental TBI. No treatment was given to the control group.
Three days after topical application, the MSCs homed to the injured parenchyma
and improved the neurological function. Topical MSCs triggered earlier
astrocytosis and reactive microglia. TBI penumbra and hippocampus had higher
cellular proliferation. Apoptosis was suppressed at hippocampus at 1 week and
reduced neuronal damaged was found in the penumbral at day 14 apoptosis.
Proteolytic neuronal injury biomarkers (alphaII-spectrin breakdown products,
SBDPs) and glial cell injury biomarker, glial fibrillary acidic protein (GFAP)
breakdown product (GBDPs) in injured cortex were also attenuated by MSCs. In the
penumbra, six genes related to axongenesis (Erbb2); growth factors (Artn, Ptn);
cytokine (IL3); cell cycle (Hdac4); and notch signaling (Hes1) were up-regulated
three days after MSC transplant. Transcriptome analysis demonstrated that 7,943
genes were differentially expressed and 94 signaling pathways were activated in
the topical MSCs transplanted onto the cortex of brain injured rats with TBI. In
conclusion, topical application offers a direct and efficient delivery of MSCs to
the brain.
PMID- 28694469
TI - Osteogenic Factor Runx2 Marks a Subset of Leptin Receptor-Positive Cells that Sit
Atop the Bone Marrow Stromal Cell Hierarchy.
AB - Bone marrow mesenchymal stem and progenitor cells (BM-MSPCs) maintain homeostasis
of bone tissue by providing osteoblasts. Although several markers have been
identified for labeling of MSPCs, these labeled cells still contain non-BM-MSPC
populations. Studies have suggested that MSPCs are observed as leptin receptor
(LepR)-positive cells, whereas osteoblasts can be classified as positive for
Runx2, a master regulator for osteoblastogenesis. Here, we demonstrate, using
Runx2-GFP reporter mice, that the LepR-labeled population contains Runx2-GFPlow
sub-population, which possesses higher fibroblastic colony-forming units (CFUs)
and mesensphere capacity, criteria for assessing stem cell activity, than the
Runx2-GFP- population. In response to parathyroid hormone (PTH), a bone anabolic
hormone, LepR+Runx2-GFPlow cells increase Runx2 expression and form multilayered
structures near the bone surface. Subsequently, the multilayered cells express
Osterix and Type I collagen alpha, resulting in generation of mature osteoblasts.
Therefore, our results indicate that Runx2 is weakly expressed in the LepR+
population without osteoblastic commitment, and the LepR+Runx2-GFPlow stromal
cells sit atop the BM stromal hierarchy.
PMID- 28694470
TI - Temperature effects on an InGaP (GaInP) 55Fe X-ray photovoltaic cell.
AB - This paper investigates the effects of temperature on an InGaP (GaInP) 55Fe X-ray
photovoltaic cell prototype for a radioisotope microbattery (also called a
nuclear microbattery). An In0.5Ga0.5P p-i-n (5 MUm i-layer) mesa photodiode was
illuminated by a standard 206 MBq 55Fe radioisotope X-ray source and
characterised over the temperature range -20 degrees C to 100 degrees C. The
electrical power output of the device reached its maximum value of 1.5 pW at a
temperature of -20 degrees C. An open circuit voltage and a short circuit
current of 0.82 V and 2.5 pA, respectively, were obtained at -20 degrees C.
While the electrical power output and the open circuit voltage decreased with
increasing temperature, an almost flat trend was found for the short circuit
current. The cell conversion efficiency decreased from 2.1% at -20 degrees C to
0.7% at 100 degrees C.
PMID- 28694471
TI - Evaluate the effect of different mmps inhibitors on adhesive physical properties
of dental adhesives, bond strength and mmp substarte activity.
AB - We have evaluated and compare the effect of different exogenous MMP inhibitors on
adhesive physical properties of dental adhesives, bond strength, micro
permeability and MMP substrate activity. 180-grit Sic paper was used to obtain
the superficial dentin surface from each and every tooth after the wet grinding
procedure. Dentin was exposed to four different MMP inhibitors to evaluate the
effect on resin adhesive dentin interface. The four groups used in study were: 2%
chlorhexidine digluconate, 2% doxycycline solution, 5% Proanthocyanidin (PR),
Control Group. We evaluated and compared the four groups at each and every step
of etching, bonding and resin application. Then, the immunolabeling was done with
the help of the secondary antibodies with the pH of 7 and the dilution of 1:20.
Amongst all the etching pretreatment groups, CHE group (Chlorhexidine etching
group) revealed highest exposure to collagen fibrils than the other groups of
etching. Then after the CHE group, the next group which has the second highest
exposure DOE group. MMP inhibitor application for time duration of 1 minute after
the etching procedures significantly improves the bond strength, exposure to
collagen fibres and uniforms the dense form of dentin hybrid layer.
PMID- 28694472
TI - The Pawnee earthquake as a result of the interplay among injection, faults and
foreshocks.
AB - The Pawnee M5.8 earthquake is the largest event in Oklahoma instrument recorded
history. It occurred near the edge of active seismic zones, similar to other M5+
earthquakes since 2011. It ruptured a previously unmapped fault and triggered
aftershocks along a complex conjugate fault system. With a high-resolution
earthquake catalog, we observe propagating foreshocks leading to the mainshock
within 0.5 km distance, suggesting existence of precursory aseismic slip. At
approximately 100 days before the mainshock, two M >= 3.5 earthquakes occurred
along a mapped fault that is conjugate to the mainshock fault. At about 40 days
before, two earthquakes clusters started, with one M3 earthquake occurred two
days before the mainshock. The three M >= 3 foreshocks all produced positive
Coulomb stress at the mainshock hypocenter. These foreshock activities within the
conjugate fault system are near-instantaneously responding to variations in
injection rates at 95% confidence. The short time delay between injection and
seismicity differs from both the hypothetical expected time scale of diffusion
process and the long time delay observed in this region prior to 2016, suggesting
a possible role of elastic stress transfer and critical stress state of the
fault. Our results suggest that the Pawnee earthquake is a result of interplay
among injection, tectonic faults, and foreshocks.
PMID- 28694473
TI - 5-LO inhibition ameliorates palmitic acid-induced ER stress, oxidative stress and
insulin resistance via AMPK activation in murine myotubes.
AB - Leukotriene B4 (LTB4) production via the 5-lipoxygenase (5-LO) pathway
contributes to the development of insulin resistance in adipose and hepatic
tissues, but the role of LTB4 in skeletal muscle is relatively unknown. Here, the
authors investigated the role of LTB4 in C2C12 myotubes in palmitic acid (PA)
induced ER stress, inflammation and insulin resistance. PA (750 MUM) evoked
lipotoxicity (ER stress, oxidative stress, inflammation and insulin resistance)
in association with LTB4 production. 5-LO inhibition reduced all the lipotoxic
effects induced by PA. On the other hand, PA did not induce cysteinyl
leukotrienes (CysLTs), which themselves had no effect on ER stress and
inflammation. The beneficial effects of 5-LO suppression from PA-induced
lipotoxicity were related with AMPK activation. In ob/ob mice, once daily oral
administration of zileuton (50, 100 mg/kg) for 5 weeks improved insulin
resistance, increased AMPK phosphorylation, and reduced LTB4 and ER stress marker
expression in skeletal muscle. These results show that 5-LO inhibition by either
zileuton or 5-LO siRNA protects C2C12 myotubes from PA-induced lipotoxicity, at
least partly via AMPK activation, and suggest that the in vivo insulin
sensitizing effects of zileuton are in part attributable to its direct action on
skeletal muscle via LTB4 downregulation followed by AMPK activation.
PMID- 28694474
TI - Comparison of Fecal Microbial Composition and Antibiotic Resistance Genes from
Swine, Farm Workers and the Surrounding Villagers.
AB - The external environment plays a critical role in shaping the structure of the
gut microbiome. One potential health threat lies in the release of antibiotic
resistant genes (ARGs) from cross-contaminated microbiomes. We focused this study
on a comparison of fecal microbial composition and antibiotic resistant genes
between farm workers, local villagers and swine. We used a high-throughput next
generation sequencing of 16S rRNA and real-time PCR for these studies. Our
results indicated that workers had less species diversity as compared to the
local villagers. Moreover, the bacterial communities of the farm workers, the
local villagers and swine feces were clearly divided into three groups. The
workers had a greater abundance of Proteobacteria as compared to swine and the
local villagers. The Clostridiaceae in the workers and swine were more abundant
than the local villagers. In addition, there were ARG differences between the
farm workers or local villager's and swine feces. The farm workers and the local
villagers had similar relative abundance except for macrolide ARGs. Taken
together, these data suggest that the swine farm environment affects the fecal
bacterial composition of swine farm workers. However, ARG spread was influenced
by factors independent of the swine farm environment.
PMID- 28694475
TI - Climate Classification is an Important Factor in Assessing Quality-of-Care Across
Hospitals.
AB - Climate is a known modulator of disease, but its impact on hospital performance
metrics remains unstudied. We assess the relationship between Koppen-Geiger
climate classification and hospital performance metrics, specifically 30-day
mortality, as reported in Hospital Compare, and collected for the period July
2013 through June 2014 (7/1/2013-06/30/2014). A hospital-level multivariate
linear regression analysis was performed while controlling for known
socioeconomic factors to explore the relationship between all-cause mortality and
climate. Hospital performance scores were obtained from 4,524 hospitals belonging
to 15 distinct Koppen-Geiger climates and 2,373 unique counties. Model results
revealed that hospital performance metrics for mortality showed significant
climate dependence (p < 0.001) after adjusting for socioeconomic factors. Climate
is a significant factor in evaluating hospital 30-day mortality rates. These
results demonstrate that climate classification is an important factor when
comparing hospital performance across the United States.
PMID- 28694476
TI - Specificity Switching Pathways in Thermal and Mass Evaporation of Multicomponent
Hydrocarbon Droplets: A Mesoscopic Observation.
AB - For well over one century, the Hertz-Knudsen equation has established the
relationship between thermal - mass transfer coefficients through a liquid -
vapour interface and evaporation rate. These coefficients, however, have been
often separately estimated for one-component equilibrium systems and their
simultaneous influences on evaporation rate of fuel droplets in multicomponent
systems have yet to be investigated at the atomic level. Here we first apply
atomistic simulation techniques and quantum/statistical mechanics methods to
understand how thermal and mass evaporation effects are controlled
kinetically/thermodynamically. We then present a new development of a hybrid
method of quantum transition state theory/improved kinetic gas theory, for
multicomponent hydrocarbon systems to investigate how concerted-distinct
conformational changes of hydrocarbons at the interface affect the evaporation
rate. The results of this work provide an important physical concept in
fundamental understanding of atomistic pathways in topological interface
transitions of chain molecules, resolving an open problem in kinetics of fuel
droplets evaporation.
PMID- 28694477
TI - Realism of modelled Indian summer monsoon correlation with the tropical Indo
Pacific affects projected monsoon changes.
AB - El Nino-Southern Oscillation (ENSO) and the Indian Ocean Dipole (IOD) tend to
exert an offsetting impact on Indian summer monsoon rainfall (ISMR), with an El
Nino event tending to lower, whereas a positive IOD tending to increase ISMR.
Simulation of these relationships in Phase Five of the Coupled Model
Intercomparison Project has not been fully assessed, nor is their impact on the
response of ISMR to greenhouse warming. Here we show that the majority of models
simulate an unrealistic present-day IOD-ISMR correlation due to an overly strong
control by ENSO. As such, a positive IOD is associated with an ISMR reduction in
the simulated present-day climate. This unrealistic present-day correlation is
relevant to future ISMR projection, inducing an underestimation in the projected
ISMR increase. Thus uncertainties in ISMR projection can be in part induced by
present-day simulation of ENSO, the IOD, their relationship and their rainfall
correlations.
PMID- 28694478
TI - MIST: Accurate and Scalable Microscopy Image Stitching Tool with Stage Modeling
and Error Minimization.
AB - Automated microscopy can image specimens larger than the microscope's field of
view (FOV) by stitching overlapping image tiles. It also enables time-lapse
studies of entire cell cultures in multiple imaging modalities. We created MIST
(Microscopy Image Stitching Tool) for rapid and accurate stitching of large 2D
time-lapse mosaics. MIST estimates the mechanical stage model parameters
(actuator backlash, and stage repeatability 'r') from computed pairwise
translations and then minimizes stitching errors by optimizing the translations
within a (4r)2 square area. MIST has a performance-oriented implementation
utilizing multicore hybrid CPU/GPU computing resources, which can process
terabytes of time-lapse multi-channel mosaics 15 to 100 times faster than
existing tools. We created 15 reference datasets to quantify MIST's stitching
accuracy. The datasets consist of three preparations of stem cell colonies seeded
at low density and imaged with varying overlap (10 to 50%). The location and size
of 1150 colonies are measured to quantify stitching accuracy. MIST generated
stitched images with an average centroid distance error that is less than 2% of a
FOV. The sources of these errors include mechanical uncertainties, specimen
photobleaching, segmentation, and stitching inaccuracies. MIST produced higher
stitching accuracy than three open-source tools. MIST is available in ImageJ at
isg.nist.gov.
PMID- 28694479
TI - Google Trends can improve surveillance of Type 2 diabetes.
AB - Recent studies demonstrate that people are increasingly looking online to assess
their health, with reasons varying from personal preferences and beliefs to
inability to book a timely appointment with their local medical practice. Records
of these activities represent a new source of data about the health of
populations, but which is currently unaccounted for by disease surveillance
models. This could potentially be useful as evidence of individuals' perception
of bodily changes and self-diagnosis of early symptoms of an emerging disease. We
make use of the Experian geodemographic Mosaic dataset in order to extract Type 2
diabetes candidate risk variables and compare their temporal relationships with
the search keywords, used to describe early symptoms of the disease on Google.
Our results demonstrate that Google Trends can detect early signs of diabetes by
monitoring combinations of keywords, associated with searches for hypertension
treatment and poor living conditions; Combined search semantics, related to
obesity, how to quit smoking and improve living conditions (deprivation) can be
also employed, however, may lead to less accurate results.
PMID- 28694480
TI - CD31hiEmcnhi Vessels Support New Trabecular Bone Formation at the Frontier Growth
Area in the Bone Defect Repair Process.
AB - CD31hiEmcnhi vessels were a subtype of vessels in the murine skeletal system,
with high levels of platelet and endothelial cell adhesion molecule-1 (PECAM
1/CD31) and endomucin (Emcn). They were reported coupling angiogenesis and
osteogenesis during bone development. We investigated the distribution of these
vessels in rat tibiae and their temporal and spatial distribution during the bone
defect repair process to improve our understanding of the importance of these
vessels. We confirmed that CD31hiEmcnhi vessels were specially distributed around
the trabecular bones near metaphysis and endosteum in rat tibiae. At 3 days post
bone injury, CD31hiEmcnhi vessels proliferated and were extensively distributed
across the entire repair area. At 7 and 14 days post-injury, these vessels
decreased but were specially distributed around the growing trabecular bones near
the frontier growth area, suggesting that these vessels support new bone
formation. The distribution of CD31hiEmcnhi vessels and the transcriptions of Hif
1alpha and VEGFA, as well as BMP2 and Osterix decreased at 7 and 14 days post
injury under osteoporotic conditions, in combination with insufficient
osteogenesis. Our research is of great significance to help understand the
important role of CD31hiEmcnhi vessels in supporting new trabecular bones
formation during bone defect repair process.
PMID- 28694481
TI - Mechanisms underlying neuro-inflammation and neurodevelopmental toxicity in the
mouse neocortex following prenatal exposure to ethanol.
AB - Fetal alcohol spectrum disorders (FASD) constitute a wide range of disorders that
arise from prenatal exposure to ethanol (EtOH). However, detailed reports
regarding the adverse effects of prenatal EtOH exposure on neocortical morphology
and its underlying pathogenic mechanisms are limited. In the present study, we
aimed to characterize the anatomical abnormalities of neocortical development and
their correlation with microglial properties and neuro-inflammation in a mouse
model of FASD. We evaluated the development and maturation of the neocortex in
ICR mice prenatally exposed to 25% (w/v) EtOH using histological and molecular
analyses. Reduced proliferation and excessive cell death were observed in the
dorsal telencephalon. Abnormal neuronal distribution, layer formation, and
dopaminergic neuronal projections were observed in the neocortex. Disruption of
microglial differentiation (M1/M2 microglial ratio) and abnormal expression of
pro-inflammatory and neurotrophic factors were induced, and these abnormalities
were ameliorated by co-treatment with an anti-inflammatory drug (pioglitazone).
FASD model mice displayed histological abnormalities, microglial abnormalities,
and neuro-inflammation in both the embryonic and newborn stages. Thus, anti
inflammatory therapeutics may provide a novel preventive approach for the
treatment of FASD.
PMID- 28694482
TI - Nature Degradable, Flexible, and Transparent Conductive Substrates from Green and
Earth-Abundant Materials.
AB - The rapid development of wearable and disposable electronic devices and the
rising awareness of environmental sustainability impose growing new demands on
the nature degradability of current electronic and energy systems. Here we report
a new type of flexible transparent conductive paper completely made from green
and earth abundant materials which are also fully degradable and recyclable.
Aluminum-doped zinc oxide (AZO) was deposited by low-temperature atomic layer
deposition (ALD) as the transparent conductive oxide (TCO) layer on transparent
cellulose nanofibril (CNF) papers. The mesoporous structure of the CNF paper
rendered strong adhesion of the AZO layer and exhibited excellent mechanical
integrity and electrical conductivity within a wide range of tensile and
compressive strains. The AZO-CNF paper could be completely dissolved in warm city
water after one-hour stirring, demonstrating an excellent nature degradability. A
flexible and transparent triboelectric nanogenerator (TENG) was further
fabricated using such AZO-CNF papers with a performance that was comparable to
other synthetic polymer-based systems. This work illustrated a new and promising
strategy of utilizing 100% green and degradable materials in novel electronic and
energy harvesting devices.
PMID- 28694483
TI - Somatic mutations in ZFHX4 gene are associated with poor overall survival of
Chinese esophageal squamous cell carcinoma patients.
AB - Recent genome-sequencing studies have revealed dozens of genes frequently mutated
in esophageal squamous cell carcinoma, but few genes are associated with
patients' clinical outcomes. Novel prognostic biomarkers are urgently needed in
the clinic. We collected both somatic mutations and clinical information of 442
Chinese esophageal squamous cell carcinoma patients from four published studies.
Survival analysis was performed to reveal the clinical significance of the
mutated genes. Dysregulation of the mutated genes was observed from public gene
expression data sets and its effects on cell migration and invasion were
investigated with siRNA-mediated silencing. Our integrated analysis revealed 26
genes significantly and frequently mutated in esophageal squamous cell carcinoma.
Importantly, mutations in ZFHX4, SPHKAP, NRXN1, KIAA1109, DNAH5 and KCNH7 were
associated with poor survival. In addition, ZFHX4 was overexpressed in tumor
tissues compared to normal controls, and knockdown of ZFHX4 in vitro
significantly inhibited cell migration and invasion. Mutations in ZFHX4 were
strongly associated with poor prognosis and the down-regulation of ZFHX4 inhibits
the progression of esophageal squamous cell carcinoma. Further investigation is
warranted to confirm the prognostic values of ZFHX4 in a prospective study.
PMID- 28694484
TI - Self-assembled alpha-Tocopherol Transfer Protein Nanoparticles Promote Vitamin E
Delivery Across an Endothelial Barrier.
AB - Vitamin E is one of the most important natural antioxidants, protecting
polyunsaturated fatty acids in the membranes of cells. Among different chemical
isoforms assimilated from dietary regimes, RRR-alpha-tocopherol is the only one
retained in higher animals. This is possible thanks to alpha-Tocopherol Transfer
Protein (alpha-TTP), which extracts alpha-tocopherol from endosomal compartments
in liver cells, facilitating its distribution into the body. Here we show that,
upon binding to its substrate, alpha-TTP acquires tendency to aggregation into
thermodynamically stable high molecular weight oligomers. Determination of the
structure of such aggregates by X-ray crystallography revealed a spheroidal
particle formed by 24 protein monomers. Oligomerization is triggered by refolding
of the N-terminus. Experiments with cultured cell monolayers demonstrate that the
same oligomers are efficiently transported through an endothelial barrier (HUVEC)
and not through an epithelial one (Caco-2). Discovery of a human endogenous
transport protein with intrinsic capability of crossing endothelial tissues opens
to new ways of drug delivery into the brain or other tissues protected by
endothelial barriers.
PMID- 28694485
TI - Circulating tumor cells in peripheral and pulmonary venous blood predict poor
long-term survival in resected non-small cell lung cancer patients.
AB - We tested the hypothesis that circulating tumor cells (CTCs) in preoperative
peripheral blood (PPB) and intraoperative pulmonary venous blood (IPVB) could
predict poor long-term survival in resected non-small cell lung cancer (NSCLC)
patients. CTCs were separated from blood using magnetic beads coated with
antibodies against epithelial-cell adhesion molecule (EpCAM) via magnetic
activated cell sorting (MACS). CTCs were quantified with fluorescence-labeled
antibodies against pan-cytokeratin through flow cytometry. CTCs were quantified
in PPB and IPVB in 23 consecutive stage I-IIIA patients with resected NSCLC. The
association between CTCs and prognosis in these patients was evaluated after a 5
year follow-up. In NSCLC patients, outcomes were assessed according to CTC levels
at surgery. NSCLC patients identified as high-risk groups exhibited >5 CTCs/15 mL
in PPB and >50 CTCs/15 mL in IPVB. Univariate Cox proportional-hazards regression
analysis showed that the CTC count in PPB or IPVB was an independent risk factor
for tumor-free surivival (TFS) and overall survival (OS). The high-risk group of
patients had a shorter median TFS (22 months vs. >60.0 months, p < 0.0012) and
shorter OS (27 months vs. >60 months, p < 0.0015). The number of CTCs counted in
PPB and IPVB was an independent risk factor for TFS and OS in resected NSCLC
patients.
PMID- 28694486
TI - CTCF binding landscape in jawless fish with reference to Hox cluster evolution.
AB - The nuclear protein CCCTC-binding factor (CTCF) contributes as an insulator to
chromatin organization in animal genomes. Currently, our knowledge of its binding
property is confined mainly to mammals. In this study, we identified CTCF
homologs in extant jawless fishes and performed ChIP-seq for the CTCF protein in
the Arctic lamprey. Our phylogenetic analysis suggests that the lamprey lineage
experienced gene duplication that gave rise to its unique paralog, designated
CTCF2, which is independent from the previously recognized duplication between
CTCF and CTCFL. The ChIP-seq analysis detected comparable numbers of CTCF binding
sites between lamprey, chicken, and human, and revealed that the lamprey CTCF
protein binds to the two-part motif, consisting of core and upstream motifs
previously reported for mammals. These findings suggest that this mode of CTCF
binding was established in the last common ancestor of extant vertebrates (more
than 500 million years ago). We analyzed CTCF binding inside Hox clusters, which
revealed a reinforcement of CTCF binding in the region spanning Hox1-4 genes that
is unique to lamprey. Our study provides not only biological insights into the
antiquity of CTCF-based epigenomic regulation known in mammals but also a
technical basis for comparative epigenomic studies encompassing the whole taxon
Vertebrata.
PMID- 28694487
TI - Evidence for rapid weathering response to climatic warming during the Toarcian
Oceanic Anoxic Event.
AB - Chemical weathering consumes atmospheric carbon dioxide through the breakdown of
silicate minerals and is thought to stabilize Earth's long-term climate. However,
the potential influence of silicate weathering on atmospheric pCO2 levels on
geologically short timescales (103-105 years) remains poorly constrained. Here we
focus on the record of a transient interval of severe climatic warming across the
Toarcian Oceanic Anoxic Event or T-OAE from an open ocean sedimentary succession
from western North America. Paired osmium isotope data and numerical modelling
results suggest that weathering rates may have increased by 215% and potentially
up to 530% compared to the pre-event baseline, which would have resulted in the
sequestration of significant amounts of atmospheric CO2. This process would have
also led to increased delivery of nutrients to the oceans and lakes stimulating
bioproductivity and leading to the subsequent development of shallow-water
anoxia, the hallmark of the T-OAE. This enhanced bioproductivity and anoxia would
have resulted in elevated rates of organic matter burial that would have acted as
an additional negative feedback on atmospheric pCO2 levels. Therefore, the
enhanced weathering modulated by initially increased pCO2 levels would have
operated as both a direct and indirect negative feedback to end the T-OAE.
PMID- 28694488
TI - Outer membrane vesicles secreted by pathogenic and nonpathogenic Bacteroides
fragilis represent different metabolic activities.
AB - Numerous studies are devoted to the intestinal microbiota and intercellular
communication maintaining homeostasis. In this regard, vesicles secreted by
bacteria represent one of the most popular topics for research. For example, the
outer membrane vesicles (OMVs) of Bacteroides fragilis play an important
nutritional role with respect to other microorganisms and promote anti
inflammatory effects on immune cells. However, toxigenic B. fragilis (ETBF)
contributes to bowel disease, even causing colon cancer. If nontoxigenic B.
fragilis (NTBF) vesicles exert a beneficial effect on the intestine, it is likely
that ETBF vesicles can be utilized for potential pathogenic implementation. To
confirm this possibility, we performed comparative proteomic HPLC-MS/MS analysis
of vesicles isolated from ETBF and NTBF. Furthermore, we performed, for the first
time, HPLC-MS/MS and GS-MS comparative metabolomic analysis for the vesicles
isolated from both strains with subsequent reconstruction of the vesicle
metabolic pathways. We utilized fluxomic experiments to validate the
reconstructed biochemical reaction activities and finally observed considerable
difference in the vesicle proteome and metabolome profiles. Compared with NTBF
OMVs, metabolic activity of ETBF OMVs provides their similarity to micro reactors
that are likely to be used for long-term persistence and implementing pathogenic
potential in the host.
PMID- 28694489
TI - High Frequency Components of Hemodynamic Shear Stress Profiles are a Major
Determinant of Shear-Mediated Platelet Activation in Therapeutic Blood
Recirculating Devices.
AB - We systematically analyzed the relative contributions of frequency component
elements of hemodynamic shear stress waveforms encountered in cardiovascular
blood recirculating devices as to overall platelet activation over time. We
demonstrated that high frequency oscillations are the major determinants for
priming, triggering and yielding activated "prothrombotic behavior" for
stimulated platelets, even if the imparted shear stress has low magnitude and
brief exposure time. Conversely, the low frequency components of the stress
signal, with limited oscillations over time, did not induce significant
activation, despite being of high magnitude and/or exposure time. In vitro data
were compared with numerical predictions computed according to a recently
proposed numerical model of shear-mediated platelet activation. The numerical
model effectively resolved the correlation between platelet activation and the
various frequency components examined. However, numerical predictions exhibited a
different activation trend compared to experimental results for different time
points of a stress activation sequence. With this study we provide a more
fundamental understanding for the mechanobiological responsiveness of circulating
platelets to the hemodynamic environment of cardiovascular devices, and the
importance of these environments in mediating life-threatening thromboembolic
complications associated with shear-mediated platelet activation. Experimental
data will guide further optimization of the thromboresistance of cardiovascular
implantable therapeutic devices.
PMID- 28694490
TI - Sea ice breakup and marine melt of a retreating tidewater outlet glacier in
northeast Greenland (81 degrees N).
AB - Rising temperatures in the Arctic cause accelerated mass loss from the Greenland
Ice Sheet and reduced sea ice cover. Tidewater outlet glaciers represent direct
connections between glaciers and the ocean where melt rates at the ice-ocean
interface are influenced by ocean temperature and circulation. However, few
measurements exist near outlet glaciers from the northern coast towards the
Arctic Ocean that has remained nearly permanently ice covered. Here we present
hydrographic measurements along the terminus of a major retreating tidewater
outlet glacier from Flade Isblink Ice Cap. We show that the region is
characterized by a relatively large change of the seasonal freshwater content,
corresponding to ~2 m of freshwater, and that solar heating during the short open
water period results in surface layer temperatures above 1 degrees C.
Observations of temperature and salinity supported that the outlet glacier is a
floating ice shelf with near-glacial subsurface temperatures at the freezing
point. Melting from the surface layer significantly influenced the ice foot
morphology of the glacier terminus. Hence, melting of the tidewater outlet
glacier was found to be critically dependent on the retreat of sea ice adjacent
to the terminus and the duration of open water.
PMID- 28694491
TI - Measuring the Energy of Ventilation and Circulation during Human Walking using
Induced Hypoxia.
AB - Energy expenditure (EE) during walking includes energy costs to move and support
the body and for respiration and circulation. We measured EE during walking under
three different oxygen concentrations. Eleven healthy, young, male lowlanders
walked on a treadmill at seven gait speeds (0.67-1.83 m s-1) on a level gradient
under normobaric normoxia (room air, 21% O2), moderate hypoxia (15% O2), and
severe hypoxia (11% O2). By comparing the hypoxia-induced elevation in heart rate
(HR [bpm]), ventilation (VE [L min-1]) with the change in energy expenditure (EE
[W]) at each speed, we were able to determine circulatory and respiratory costs.
In a multivariate model combining HR and VE, respiratory costs were 0.44 +/- 0.15
W per each L min-1 increase in VE, and circulatory costs were 0.24 +/- 0.05 W per
each bpm increase in HR (model adjusted r2 = 0.97, p < 0.001). These VE costs
were substantially lower than previous studies that ignored the contribution of
HR to cardiopulmonary work. Estimated HR costs were consistent with, although
somewhat higher than, measures derived from catheterization studies.
Cardiopulmonary costs accounted for 23% of resting EE, but less than 5% of net
walking costs (i.e., with resting EE subtracted).
PMID- 28694492
TI - Chronic lung inflammation primes humoral immunity and augments antipneumococcal
resistance.
AB - Airway epithelial cells (AECs) display remarkable plasticity in response to
infectious stimuli and their functional adaptations are critical for
antimicrobial immunity. However, the roles of AECs and humoral mediators to host
defense in non-communicable lung inflammation remain elusive. We dissected
pulmonary defense against Streptococcus pneumoniae in hosts with pre-existing
inflammatory conditions (SPC-HAxTCR-HA mice). Lung tissue transcriptomics and
bronchoalveolar lavage fluid (BALF) proteomics revealed an induction of humoral
defense mechanisms in inflamed lungs. Accordingly, besides antibacterial proteins
and complement components being overrepresented in inflamed lungs, elevated
polymeric immunoglobulin receptor (pIgR)-expression in AECs correlated with
increased secretory immunoglobulin (SIg) transport. Consequently, opsonization
assays revealed augmented pneumococcal coverage by SIgs present in the BALF of
SPC-HAxTCR-HA mice, which was associated with enhanced antipneumococcal
resistance. These findings emphasize the immunologic potential of AECs as well as
their central role in providing antibacterial protection and put forward pIgR as
potential target for therapeutic manipulation in infection-prone individuals.
PMID- 28694493
TI - Ultraviolet GaN Light-Emitting Diodes with Porous-AlGaN Reflectors.
AB - A GaN/AlGaN ultraviolet light emitting diode (UV-LED) structure with a porous
AlGaN reflector structure has been demonstrated. Inside the UV-LED, the n+
AlGaN/undoped-AlGaN stack structure was transformed into a porous-AlGaN/undoped
AlGaN stack structure through a doping-selective electrochemical etching process.
The reflectivity of the porous AlGaN reflector was 93% at 374 nm with a stop
bandwidth of 35 nm. In an angle-dependent reflectance measurement, the central
wavelength of the porous AlGaN reflector had blueshift phenomenon by increasing
light-incident angle from 10 degrees to 50 degrees . A cut-off wavelength was
observed at 349 nm due to the material absorption of the porous-AlGaN/u-AlGaN
stack structure. In the treated UV-LED structure, the photoluminescence emission
wavelength was measured at 362 nm with a 106 degrees divergent angle covered by
the porous-AlGaN reflector. The light output power of the treated UV-LED
structure was higher than that of the non-treated UV-LED structure due to the
high light reflectance on the embedded porous AlGaN reflector.
PMID- 28694494
TI - Differential co-expression analysis reveals a novel prognostic gene module in
ovarian cancer.
AB - Ovarian cancer is one of the most significant disease among gynecological
disorders that women suffered from over the centuries. However, disease-specific
and effective biomarkers were still not available, since studies have focused on
individual genes associated with ovarian cancer, ignoring the interactions and
associations among the gene products. Here, ovarian cancer differential co
expression networks were reconstructed via meta-analysis of gene expression data
and co-expressed gene modules were identified in epithelial cells from ovarian
tumor and healthy ovarian surface epithelial samples to propose ovarian cancer
associated genes and their interactions. We propose a novel, highly
interconnected, differentially co-expressed, and co-regulated gene module in
ovarian cancer consisting of 84 prognostic genes. Furthermore, the specificity of
the module to ovarian cancer was shown through analyses of datasets in nine other
cancers. These observations underscore the importance of transcriptome based
systems biomarkers research in deciphering the elusive pathophysiology of ovarian
cancer, and here, we present reciprocal interplay between candidate ovarian
cancer genes and their transcriptional regulatory dynamics. The corresponding
gene module might provide new insights on ovarian cancer prognosis and treatment
strategies that continue to place a significant burden on global health.
PMID- 28694495
TI - Functional determinants of protein assembly into homomeric complexes.
AB - Approximately half of proteins with experimentally determined structures can
interact with other copies of themselves and assemble into homomeric complexes,
the overwhelming majority of which (>96%) are symmetric. Although homomerisation
is often assumed to a functionally beneficial result of evolutionary selection,
there has been little systematic analysis of the relationship between homomer
structure and function. Here, utilizing the large numbers of structures and
functional annotations now available, we have investigated how proteins that
assemble into different types of homomers are associated with different
biological functions. We observe that homomers from different symmetry groups are
significantly enriched in distinct functions, and can often provide simple
physical and geometrical explanations for these associations in regards to
substrate recognition or physical environment. One of the strongest associations
is the tendency for metabolic enzymes to form dihedral complexes, which we
suggest is closely related to allosteric regulation. We provide a physical
explanation for why allostery is related to dihedral complexes: it allows for
efficient propagation of conformational changes across isologous (i.e. symmetric)
interfaces. Overall we demonstrate a clear relationship between protein function
and homomer symmetry that has important implications for understanding protein
evolution, as well as for predicting protein function and quaternary structure.
PMID- 28694496
TI - Tree functional types simplify forest carbon stock estimates induced by carbon
concentration variations among species in a subtropical area.
AB - Forests contain one of the world's largest carbon (C) pools and represent
opportunities for cost-effective climate change mitigation through programmes
such as the United Nations-led "Reducing Emissions from Deforestation and Forest
Degradation" Programme (REDD). Generic estimates for the conversion of forest
biomass into C stock are not sufficiently accurate for assessing the utility of
harvesting forest to offset carbon dioxide emissions, currently under
consideration by the REDD Programme. We examined the variation in C concentration
among tree species and tree functional types (classified based on leaf
morphological and phenological traits) in a subtropical forest and evaluated the
effects of these variations on stand-level estimations of C stock. This study was
conducted in the Paiyashan Forest State Farm and the Dashanchong Forest Park,
Hunan Province, China. C concentrations differed significantly among tree species
(P < 0.0001) and were significantly higher in gymnosperm than angiosperm species.
Estimations of stand C stocks were similar using either functional types or
species- and tissue-specific C concentrations. The use of functional type
classification to estimate stand C stock is an effective tool for implementing C
sequestration trade and C credit programmes and the UN-REDD Programme in
subtropical forests.
PMID- 28694497
TI - Role of visual and olfactory cues in sex recognition in butterfly Cethosia cyane
cyane.
AB - Butterflies use multiple signals, including visual, olfactory and tactile cues,
to identify same- and opposite-sex individuals during courtship. In this study of
the sexually dimorphic butterfly Cethosia cyane cyane, we explored the roles of
visual and olfactory cues in conspecific mate recognition during courtship. Our
results showed that males took the initiative in actively chasing females during
courtship using only visual cues. Males could distinguish the gender of
conspecifics using visual cues alone. The size and color of the wings differ
significantly between the sexes. Behavioral assays showed that males visually
recognized females not by wing size, but by their sexually specific wing color.
The movement pattern of the model also exerted some influence on male courtship
chasing behavior. A total of 21 volatiles were detected in the bodies of adults,
but only cedrol played a role in the process of male recognition of females at
close range. Therefore, males rely on both visual and olfactory cues to
distinguish females during courtship. Visual cues play a major role in attracting
males at the beginning of the courtship chase, while olfactory cues play a role
in accurately identifying partners at close range.
PMID- 28694498
TI - Analysis of positive and negative allosteric modulation in metabotropic glutamate
receptors 4 and 5 with a dual ligand.
AB - As class C GPCRs and regulators of synaptic activity, human metabotropic
glutamate receptors (mGluRs) 4 and 5 are prime targets for allosteric modulation,
with mGlu5 inhibition or mGlu4 stimulation potentially treating conditions like
chronic pain and Parkinson's disease. As an allosteric modulator that can bind
both receptors, 2-Methyl-6-(phenylethynyl)pyridine (MPEP) is able to negatively
modulate mGlu5 or positively modulate mGlu4. At a structural level, how it
elicits these responses and how mGluRs undergo activation is unclear. Here, we
employ homology modelling and 30 us of atomistic molecular dynamics (MD)
simulations to probe allosteric conformational change in mGlu4 and mGlu5, with
and without docked MPEP. Our results identify several structural differences
between mGlu4 and mGlu5, as well as key differences responsible for MPEP-mediated
positive and negative allosteric modulation, respectively. A novel mechanism of
mGlu4 activation is revealed, which may apply to all mGluRs in general. This
involves conformational changes in TM3, TM4 and TM5, separation of intracellular
loop 2 (ICL2) from ICL1/ICL3, and destabilization of the ionic-lock. On the other
hand, mGlu5 experiences little disturbance when MPEP binds, maintaining its
inactive state with reduced conformational fluctuation. In addition, when MPEP is
absent, a lipid molecule can enter the mGlu5 allosteric pocket.
PMID- 28694499
TI - Cystatin D (CST5): An ultra-early inflammatory biomarker of traumatic brain
injury.
AB - Traumatic brain injury (TBI) is set to become the leading cause of neurological
disability across all age groups. Currently, no reliable biomarkers exist to help
diagnose the severity of TBI to identify patients who are at risk of developing
secondary injuries. Thus, the discovery of reliable biomarkers for the management
of TBI would improve clinical interventions. Inflammatory markers are
particularly suited for biomarker discovery as TBI leads to very early
alterations in inflammatory proteins. Using the Proseek Multiplex Inflammation
assay, we measured in patients that had suffered mild TBI (n = 10) or severe TBI
(n = 10) with extra-cranial injury or extracranial injury only (EC) (n = 10), 92
inflammation-associated proteins in serum obtained: <1 hr (within 1-hour), 4-12
hr and 48-72 hr post injury. Changes were compared to healthy volunteers (HV).
Our results identified CST5, AXIN1 and TRAIL as novel early biomarkers of TBI.
CST5 identified patients with severe TBI from all other cohorts and importantly
was able to do so within the first hour of injury. AXIN1 and TRAIL were able to
discriminate between TBI and HV at <1 hr. We conclude that CST5, AXIN1 and TRAIL
are worthy of further study in the context of a pre-hospital or pitch-side test
to detect brain injury.
PMID- 28694500
TI - Resistance exercise initiates mechanistic target of rapamycin (mTOR)
translocation and protein complex co-localisation in human skeletal muscle.
AB - The mechanistic target of rapamycin (mTOR) is a central mediator of protein
synthesis in skeletal muscle. We utilized immunofluorescence approaches to study
mTOR cellular distribution and protein-protein co-localisation in human skeletal
muscle in the basal state as well as immediately, 1 and 3 h after an acute bout
of resistance exercise in a fed (FED; 20 g Protein/40 g carbohydrate/1 g fat) or
energy-free control (CON) state. mTOR and the lysosomal protein LAMP2 were highly
co-localised in basal samples. Resistance exercise resulted in rapid
translocation of mTOR/LAMP2 towards the cell membrane. Concurrently, resistance
exercise led to the dissociation of TSC2 from Rheb and increased in the co
localisation of mTOR and Rheb post exercise in both FED and CON. In addition,
mTOR co-localised with Eukaryotic translation initiation factor 3 subunit F
(eIF3F) at the cell membrane post-exercise in both groups, with the response
significantly greater at 1 h of recovery in the FED compared to CON. Collectively
our data demonstrate that cellular trafficking of mTOR occurs in human muscle in
response to an anabolic stimulus, events that appear to be primarily influenced
by muscle contraction. The translocation and association of mTOR with positive
regulators (i.e. Rheb and eIF3F) is consistent with an enhanced mRNA
translational capacity after resistance exercise.
PMID- 28694501
TI - Retinal Blood Flow Velocity Change in Parafoveal Capillary after Topical
Tafluprost Treatment in Eyes with Primary Open-angle Glaucoma.
AB - Although ocular circulation at the retina and optic disc is known to be
associated with the pathology of glaucoma, direct measurement of blood flow
velocity has been difficult to obtain. This prospective observational study
enrolled 11 consecutive patients with treatment-naive primary open-angle glaucoma
(POAG) and 11 healthy subjects, and the effects of topical tafluprost treatment
on ocular circulation were examined at baseline and at 1, 4, and 12 weeks after
initiating treatment with topical tafluprost on POAG patients using multiple
modalities, which include adaptive optics scanning laser ophthalmoscopy (AOSLO).
Baseline mean intraocular pressure (IOP) was significantly higher and mean
parafoveal blood flow velocity (pBFV) was significantly lower in POAG eyes than
in healthy eyes. Mean IOP was significantly decreased (1 week, -19.1%; 4 weeks,
17.7%; and 12 weeks, -23.5%; all P < 0.001) and mean pBFV was significantly
increased from the baseline at all follow-up periods after initiating treatment
(1 week, 14.9%, P = 0.007; 4 weeks, 21.3%, P < 0.001; and 12 weeks, 14.3%, P =
0.002). These results reveal that tafluprost may not only lower IOP but may also
improve retinal circulation in POAG eyes and AOSLO may be useful to evaluate
retinal circulatory change after treatment.
PMID- 28694502
TI - G-protein coupled receptor 64 is required for decidualization of endometrial
stromal cells.
AB - Although GPR64 has an important role for male fertility, its physiological roles
in the female reproductive system are still unknown. In the present study,
immunohistochemical analysis reveals a spatiotemporal expression of GPR64 in the
uterus during early pregnancy. Observation of remarkable induction of GPR64
expression in uterine decidual cells points to its potential physiological
significance on decidualization. The decidualization of uterine stromal cells is
a key event in implantation. Progesterone (P4) signaling is crucial for the
decidualization of the endometrial stromal cells for successful pregnancy.
Therefore, we examined ovarian steroid hormone regulation of GPR64 expression in
the murine uterus. P4 induced GPR64 expression in the epithelial and stromal
cells of the uterus in ovariectomized wild-type mice, but not in PRKO mice. ChIP
analysis confirmed that PGR proteins were recruited on progesterone response
element of Gpr64 gene in the uteri of wild-type mice treated with P4.
Furthermore, the expression of GPR64 was increased in human endometrial stromal
cells (hESCs) during in vitro decidualization. Interestingly, small interfering
RNA (siRNA)-mediated knockdown of GPR64 in hESCs remarkably reduced
decidualization. These results suggest that Gpr64 has a crucial role in the
decidualization of endometrial stromal cells.
PMID- 28694503
TI - CD44v8-10 as a potential theranostic biomarker for targeting disseminated cancer
cells in advanced gastric cancer.
AB - Gastric cancer is the third most common cause of cancer mortality, and the
survival rate of stage IV advanced gastric cancer (AGC) patients with distant
metastasis is very low. Thus, the detection and eradication of disseminated
cancer cells by targeting cell surface molecules in AGC would improve patient
survival. The hyaluronic acid receptor, CD44, has various isoforms generated by
alternative splicing, and some isoforms are known to be correlated to gastric
cancer. In this study, to find out the most appropriate CD44v for targeting AGC,
we analysed the expression differences of CD44 isoforms at the mRNA level in
stomach cancer cell lines as well as in 74 patients with AGC by using exon
specific qRT-PCR. Among the CD44v isoforms, CD44v8-10 was determined as the most
promising biomarker for the development of theranostic agents of gastric cancer.
Next, we synthesised the conjugate of anti-CD44v9 antibody with near-infrared
fluorophore or photosensitiser, and then demonstrated its feasibility for target
cell-specific imaging and photoimmunotherapy in gastric cancer. As a result,
these conjugates have clearly demarcated the surface of CD44v8-10 expressing
cancer cells and showed efficient phototoxic effects. Therefore, this study
revealed that CD44v8-10 is the efficient theranostic biomarker to target
disseminated cancer cells in AGC.
PMID- 28694504
TI - Melatonin alleviates chilling stress in cucumber seedlings by up-regulation of
CsZat12 and modulation of polyamine and abscisic acid metabolism.
AB - To obtain new insights into the mechanisms of the positive effects of exogenous
melatonin applications to cucumber seedlings during chilling, we investigated its
role in regulating photosynthesis, the transcription level of csZat12 and the
metabolism of polyamines (PAs) and of abscisic acid (ABA). The negative effects
of chilling were clearly alleviated in cucumber seedlings by irrigation with 200
MUM melatonin solution. This was evidenced by alleviation of the decline in net
photosynthesis rate and also in electrolyte leakage in chilled plants. The
reasons for this can be explained as follows. First, melatonin up-regulates
CsZat12, an important stress-related gene. Second, melatonin increases the
content of putrescine (Put) and spermidine (Spd) and stabilized spermine (Spm) by
altering the activity of the PA metabolic enzymes. And, third, ABA is also
involved in these effects as melatonin modulated the expression of the key ABA
biosynthesis genes (CsNCED1 and CsNCED2) and also the key ABA catabolism genes
(CsCYP707A1 and CsCYP707A2). This study provides new evidence suggesting
melatonin mitigates chilling stress in cucumber by up-regulating the expression
of CsZat12 and by modulating the metabolism of PAs and ABA.
PMID- 28694505
TI - Presence of diabetes autoantigens in extracellular vesicles derived from human
islets.
AB - Beta-cell (beta-cell) injury is the hallmark of autoimmune diabetes. However, the
mechanisms by which autoreactive responses are generated in susceptible
individuals are not well understood. Extracellular vesicles (EV) are produced by
mammalian cells under normal and stressed physiological states. They are an
important part of cellular communication, and may serve a role in antigen
processing and presentation. We hypothesized that isolated human islets in
culture produce EV that contain diabetes autoantigens (DAA) from these otherwise
normal, non-diabetic donors. Here we report the caspase-independent production of
EV by human islets in culture, and the characterization of DAA glutamic acid
decarboxylase 65 (GAD65) and zinc transporter 8 (ZnT8), as well as the beta-cell
resident glucose transporter 2 (Glut2), present within the EV.
PMID- 28694506
TI - Universality of the Phytophthora mating hormones and diversity of their
production profile.
AB - Sexual reproduction of the plant pest Phytophthora is regulated by two mating
hormones alpha1 and alpha2, which are acyclic oxygenated diterpenes first
isolated from P. nicotianae A1 and A2 mating types, respectively. A previous
report suggested the universality of these factors within this genus. To confirm
this concept, we investigated 80 strains (19 species) of Phytophthora and a
related genus, not only for the responsiveness to mating hormones but also for
their productivity. The results indicated that among the 55 heterothallic
strains, 24 (44%) responded to a mating hormone and 40 (73%) produced one or both
hormones. These findings demonstrate the interspecies universality of mating
hormones within the genus Phytophthora. Hormone productivity was found to be
highly diverse and dependent on the strains used. Although the A2 mating type has
been regarded as the alpha2 producer, 19 (59%) of the 32 A2-type strains produced
both the hormones and two A2-type strains exclusively produced alpha1 in high
yields. These results indicate that hormone biosynthesis in Phytophthora is
universal but highly diverse and complex, and varies with culture conditions,
providing us valuable information for future studies on the mechanism of mating
hormone biosynthesis of Phytophthora.
PMID- 28694507
TI - A Novel Highly Sensitive NO2 Sensor Based on Perovskite Na0.5+xBi0.5TiO3-delta
Electrolyte.
AB - NOx is one of dangerous air pollutants, and the demands for reliable sensors to
detect NOx are extremely urgent recently. Conventional fluorite-phase YSZ used
for NOx sensor requires higher operating temperature to obtain desirable oxygen
ion conductivity. In this work, perovskite-phase Na0.5Bi0.5TiO3 (NBT) oxygen
conductor was chosen as the solid electrolyte to fabricate a novel highly
sensitive NO2 sensor with CuO as the sensing electrode and Pt as reference
electrode. Na dopped Na0.5Bi0.5TiO3 greatly improved the sensing performance of
this sensor. The optimal sensor based on Na0.51Bi0.50TiO3-delta exhibited good
response-recovery characteristics to NO2 and the response current values were
almost linear to NO2 concentrations in the range of 50-500 ppm at 400-600
degrees C. The response current value towards NO2 reached maximum 11.23 MUA at
575 degrees C and the value on NO2 is much higher than other gases (CH4, C2H4,
C3H6, C3H8, CO), indicating good selectivity for detecting NO2. The response
signals of the sensor were slightly affected by coexistent O2 varying from 2 to
21 vol% at 575 degrees C. The response current value decreased only 4.9% over 2
months, exhibiting the potential application in motor vehicles.
PMID- 28694508
TI - Effects of suspended sediments on the sponge holobiont with implications for
dredging management.
AB - Dredging can cause high suspended sediment concentrations (SSC) in the water
column, posing a hazard to filter feeding organisms like sponges as sediment may
clog their aquiferous systems and reduce feeding. In order to provide pressure
response values for sponges to SSC and tease apart the cause:effect pathways of
dredging pressures, five heterotrophic and phototrophic species were
experimentally exposed to a range of dredging-relevant SSC of up to 100 mg L-1,
with light compensation across treatments to ensure that SSC was the primary
physical parameter. This study shows that some sponge species exposed to high SSC
(>=23 mg L-1) for extended periods (28 d) have lower survival, increased necrosis
and depletion of energy reserves. In contrast, SSC of <=10 mg L-1 caused few, if
any, negative effects and is thus suggested as a prudent sub-lethal threshold for
sponges. Microbial communities did not change significantly among SSC treatments,
although a nutritional shift from mixotrophy towards increased phototrophy was
detected for some sponge species exposed to high SSC. Importantly however, it is
expected that the combined effect of SSC with low light availability and sediment
smothering as occurs during dredging operations will increase the negative
effects on sponges.
PMID- 28694509
TI - Generation of path-polarization hyperentanglement using quasi-phase-matching in
quasi-periodic nonlinear photonic crystal.
AB - A compact scheme for the generation of path-polarization entangled photon pairs
is proposed by using a quasi-periodic nonlinear photonic crystal to
simultaneously accomplish four spontaneous parametric down-conversion processes.
Moreover, we report experimental scheme to measure the polarization entanglement
and path entanglement separately and theoretically get numerical results that
verify some predictions about the hyperentanglement. This method can be expanded
for the generation of multi-partite and two-photon path-polarization
hyperentanglement in a single quasi-periodic nonlinear photonic crystal
structure. This compact quantum light source can be used as a significant
ingredient in quantum information science.
PMID- 28694510
TI - Non-invasive imaging of engineered human tumors in the living chicken embryo.
AB - The growing interest in engineered tumor models prompted us to devise a method
for the non-invasive assessment of such models. Here, we report on
bioluminescence imaging (BLI) for the assessment of engineered tumor models in
the fertilized chicken egg, i.e, chick chorioallantoic membrane (CAM) assay. One
prostate cancer (PC-3) and two osteosarcoma (MG63 and HOS) cell lines were
modified with luciferase reporter genes. To create engineered tumors, these cell
lines were seeded either onto basement membrane extract (BME) or gelfoam
scaffolds, and subsequently grafted in vivo onto the CAM. BLI enabled non
invasive, specific detection of the engineered tumors on the CAM in the living
chicken embryo. Further, BLI permitted daily, quantitative monitoring of the
engineered tumors over the course of up to 7 days. Data showed that an
extracellular matrix (ECM) composed of BME supported growth of reporter gene
marked PC-3 tumors but did not support MG63 or HOS tumor growth. However, MG63
tumors engineered on the collagen-based gelfoam ECM showed a temporal
proliferation burst in MG63 tumors. Together, the data demonstrated imaging of
engineered human cancer models in living chicken embryos. The combination of CAM
assay and BLI holds significant potential for the examination of a broad range of
engineered tumor models.
PMID- 28694511
TI - Bi-directional high speed domain wall motion in perpendicular magnetic anisotropy
Co/Pt double stack structures.
AB - We report bi-directional domain wall (DW) motion along and against current flow
direction in Co/Pt double stack wires with Ta capping. The bi-directionality is
achieved by application of hard-axis magnetic field favoring and opposing the
Dzyloshinskii-Moriya interaction (DMI), respectively. The speed obtained is
enhanced when the hard-axis field favors the DMI and is along the current flow
direction. Co/Pt double stack is a modification proposed for the high spin-orbit
torque strength Pt/Co/Ta stack, to improve its thermal stability and
perpendicular magnetic anisotropy (PMA). The velocity obtained reduces with
increase in Pt spacer thickness due to reduction in DMI and enhances on
increasing the Ta capping thickness due to higher SOT strength. The velocity
obtained is as high as 530 m/s at a reasonable current density of 1 * 1012 A/m2
for device applications. The low anisotropy of the device coupled with the
application of hard-axis field aids the velocity enhancement by preventing Walker
breakdown.
PMID- 28694512
TI - Pet-directed speech draws adult dogs' attention more efficiently than Adult
directed speech.
AB - Humans speak to dogs using a special speech register called Pet-Directed Speech
(PDS) which is very similar to Infant-Directed Speech (IDS) used by parents when
talking to young infants. These two type of speech share prosodic features that
are distinct from the typical Adult-Directed Speech (ADS): a high pitched voice
and an increased pitch variation. So far, only one study has investigated the
effect of PDS on dogs' attention. We video recorded 44 adult pet dogs and 19
puppies when listening to the same phrase enounced either in ADS or in PDS or in
IDS. The phrases were previously recorded and were broadcasted via a loudspeaker
placed in front of the dog. The total gaze duration of the dogs toward the
loudspeaker, was used as a proxy of attention. Results show that adult dogs are
significantly more attentive to PDS than to ADS and that their attention
significantly increases along with the rise of the fundamental frequency of
human' speech. It is likely that the exaggerated prosody of PDS is used by owners
as an ostensive cue for dogs that facilitates the effectiveness of their
communication, and should represent an evolutionarily determined adaptation that
benefits the regulation and maintenance of their relationships.
PMID- 28694513
TI - Hybrid perovskite solar cells fabricated from guanidine hydroiodide and tin
iodide.
AB - For the search of new metal-halide perovskite solar cell materials, tolerance
factors are calculated from the ionic radius of each site and are often utilized
as the critical factors to expect the materials forming perovskite structure. As
one of such amine hydrohalides, guanidine hydroiodide (GI) is reported not to
react with PbI2. However, in this paper, we report the product of GI and SnI2
reaction, its visible light absorption, X-ray diffraction, and its solar cell
operation, in spite of the more disadvantageous tolerance factor of SnI2 than
PbI2. We also report the thermal stability of GI, enabling precise control of
vacuum deposition, and utilization of co-evaporant induced crystallization method
during the vacuum evaporation of the SnI2 film, which resulted in enlarging the
SnI2 crystals and improving the short circuit current density of the solar cell.
PMID- 28694514
TI - Within-host Evolution of Segments Ratio for the Tripartite Genome of Alfalfa
Mosaic Virus.
AB - The existence of multipartite viruses is an intriguing mystery in evolutionary
virology. Several hypotheses suggest benefits that should outweigh the costs of a
reduced transmission efficiency and of segregation of coadapted genes associated
with encapsidating each segment into a different particle. Advantages range from
increasing genome size despite high mutation rates, faster replication, more
efficient selection resulting from reassortment during mixed infections, better
regulation of gene expression, or enhanced virion stability and cell-to-cell
movement. However, support for these hypotheses is scarce. Here we report
experiments testing whether an evolutionary stable equilibrium exists for the
three genomic RNAs of Alfalfa mosaic virus (AMV). Starting infections with
different segment combinations, we found that the relative abundance of each
segment evolves towards a constant ratio. Population genetic analyses show that
the segment ratio at this equilibrium is determined by frequency-dependent
selection. Replication of RNAs 1 and 2 was coupled and collaborative, whereas the
replication of RNA 3 interfered with the replication of the other two. We found
that the equilibrium solution is slightly different for the total amounts of RNA
produced and encapsidated, suggesting that competition exists between all RNAs
during encapsidation. Finally, we found that the observed equilibrium appears to
be host-species dependent.
PMID- 28694515
TI - Physical Binding of Endothelial MCAM and Neural Transmembrane Protease Matriptase
Novel Cell Adhesion in Neural Stem cell Vascular Niche.
AB - Brain neural stem cells and transit amplifying cells in the subventricular zone
(SVZ) of the lateral ventricles are in direct contact with the microvascular
endothelium. The mechanisms/molecules of direct cell contact in the SVZ
neurovascular niche are not fully understood. We previously showed that neural
stem/progenitor (NS/P) cells induce brain endothelial signaling in direct cell
contact through matriptase (MTP) on NS/P cell surface. In the present study,
using pull-down and LC-MS/MS, we identified melanoma cell adhesion molecule
(MCAM) the brain endothelial molecule that interacts with MTP. MCAM physically
binds to the CUB domains of MTP and induces a chain of brain endothelial
signaling including p38MAPK activation, GSK3beta inactivation and subsequently
beta-catenin activation; none of these signaling events occurred when either MTP
or MCAM is deleted. MTP-MCAM binding and induction of endothelial signaling were
all sensitive to cholera toxin. Together, we identified key molecules that may
represent a mechanism in neural stem cell vascular niche regulation.
PMID- 28694516
TI - Revealing the influence of Cyano in Anchoring Groups of Organic Dyes on
Adsorption Stability and Photovoltaic Properties for Dye-Sensitized Solar Cells.
AB - Determining an ideal adsorption configuration for a dye on the semiconductor
surface is an important task in improving the overall efficiency of dye
sensitized solar cells. Here, we present a detailed investigation of different
adsorption configurations of designed model dyes on TiO2 anatase (101) surface
using first principles methods. Particularly, we aimed to investigate the
influence of cyano group in the anchoring part of dye on its adsorption stability
and the overall photovoltaic properties such as open circuit voltage, electron
injection ability to the surface. Our results indicate that the inclusion of
cyano group increases the stability of adsorption only when it adsorbs via CN
with the surface and it decreases the photovoltaic properties when it does not
involve in binding. In addition, we also considered full dyes based on the
results of model dyes and investigated the different strength of acceptor
abilities on stability and electron injection ability. Among the various
adsorption configurations considered here, the bidentate bridging mode (A3) is
more appropriate one which has higher electron injection ability, larger VOC
value and more importantly it has higher dye loading on the surface.
PMID- 28694517
TI - The lateral parabrachial nucleus, but not the thalamus, mediates thermosensory
pathways for behavioural thermoregulation.
AB - Thermoregulatory behaviour, such as migration to a comfortable thermal
environment, is a representative innate animal behaviour and facilitates
effective autonomic regulation of body temperature with a reduced cost of
resources. Here we determine the central thermosensory ascending pathway that
transmits information on environmental temperature from cutaneous thermoreceptors
to elicit thermoregulatory behaviour. To examine the contribution of the
spinothalamocortical pathway, which is known to mediate thermosensory
transmission for perception of skin temperature, we lesioned thalamic regions
mediating this pathway in rats. Thalamic-lesioned rats showed compromised
electroencephalographic responses in the primary somatosensory cortex to changes
in skin temperature, indicating functional ablation of the spinothalamocortical
pathway. However, these lesioned rats subjected to a two-floor innocuous thermal
plate preference test displayed intact heat- and cold-avoidance thermoregulatory
behaviours. We then examined the involvement of the lateral parabrachial nucleus
(LPB), which mediates cutaneous thermosensory signaling to the thermoregulatory
center for autonomic thermoregulation. Inactivation of neurons in the LPB
eliminated both heat- and cold-avoidance thermoregulatory behaviours and ablated
heat defense. These results demonstrate that the LPB, but not the thalamus,
mediates the cutaneous thermosensory neural signaling required for behavioural
thermoregulation, contributing to understanding of the central circuit that
generates thermal comfort and discomfort underlying thermoregulatory behaviours.
PMID- 28694518
TI - PDK1 plays a vital role on hematopoietic stem cell function.
AB - 3-Phosphoinositide-dependent protein kinase 1 (PDK1) is a pivotal regulator in
the phosphoinositide 3-kinase (PI3K)-Akt signaling pathway that have been shown
to play key roles in the functional development of B and T cells via activation
of AGC protein kinases during hematopoiesis. However, the role of PDK1 in HSCs
has not been fully defined. Here we specifically deleted the PDK1 gene in the
hematopoietic system and found that PDK1-deficient HSCs exhibited impaired
function and defective lineage commitment abilities. Lack of PDK1 caused HSCs to
be less quiescent and to produce a higher number of phenotypic HSCs and fewer
progenitors. PDK1-deficient HSCs were also unable to reconstitute the
hematopoietic system. Notably, HSC function was more dependent on PDK1 than on
mTORC2, which indicates that PDK1 plays a dominant role in the Akt-mediated
regulation of HSC function. PDK1-deficient HSCs also exhibited reduced ROS
levels, and treatment of PDK1-deficient HSCs with L-butathioninesulfoximine in
vitro elevated the low ROS level and promoted colony formation. Therefore, PDK1
appears to contribute to HSC function partially via regulating ROS levels.
PMID- 28694519
TI - In vitro imaging of bacteria using 18F-fluorodeoxyglucose micro positron emission
tomography.
AB - Positron emission tomography (PET) with fluorine-18-fluorodeoxyglucose (18F-FDG)
can be applied to detect infection and inflammation. However, it was so far not
known to what extent bacterial pathogens may contribute to the PET signal.
Therefore, we investigated whether clinical isolates of frequently encountered
bacterial pathogens take up 18F-FDG in vitro, and whether FDG inhibits bacterial
growth as previously shown for 2-deoxy-glucose. 22 isolates of Gram-positive and
Gram-negative bacterial pathogens implicated in fever and inflammation were
incubated with 18F-FDG and uptake of 18F-FDG was assessed by gamma-counting and
uPET imaging. Possible growth inhibition by FDG was assayed with Staphylococcus
aureus and the Gram-positive model bacterium Bacillus subtilis. The results show
that all tested isolates accumulated 18F-FDG actively. Further, 18F-FDG uptake
was hampered in B. subtilis pts mutants impaired in glucose uptake. FDG inhibited
growth of S. aureus and B. subtilis only to minor extents, and this effect was
abrogated by pts mutations in B. subtilis. These observations imply that bacteria
may contribute to the signals observed in FDG-PET infection imaging in vivo.
Active bacterial FDG uptake is corroborated by the fact that the B. subtilis
phosphotransferase system is needed for 18F-FDG uptake, while pts mutations
protect against growth inhibition by FDG.
PMID- 28694520
TI - Herbal formula YYJD inhibits tumor growth by inducing cell cycle arrest and
senescence in lung cancer.
AB - Lung cancer represents a major cause of cancer-related death worldwide. Although
various tactics and anti-tumor drugs have been used to improve curative effects,
five-year survival rate of lung cancer patients remains poor. In this study, we
investigated the action and underlying mechanisms of our recently optimized
Chinese herbal formula Yangyinjiedu (YYJD) against lung cancer. YYJD
significantly inhibits the proliferation of lung cancer cell lines (95-D, A549,
H460 and H1975) by inducing cell cycle arrest and senescence in a dose-dependent
manner. In particular, YYJD induces significant G2/M phase arrest and inhibits
the colony formation of lung cancer cells. Moreover, we found that administration
of YYJD could inhibit the growth of xenografted lung cancer cells in nude mice
without loss in body weight. Our findings suggest that the herbal formula YYJD is
a potential anti-tumor agent against lung cancer.
PMID- 28694521
TI - Genome-wide analysis of long noncoding RNA profiling in PRRSV-infected PAM cells
by RNA sequencing.
AB - Porcine reproductive and respiratory syndrome (PRRS) is a major threat to the
global swine industry and causes tremendous economic losses. Its causative agent,
porcine reproductive and respiratory syndrome virus (PRRSV), primarily infects
immune cells, such as porcine alveolar macrophages and dendritic cells. PRRSV
infection results in immune suppression, antibody-dependent enhancement, and
persistent infection. Highly pathogenic strains in China cause high fever and
severe inflammatory responses in the lungs. However, the pathogenesis of PRRSV is
still not fully understood. In this study, we analysed the long noncoding RNA
(lncRNA) and mRNA expression profiles of the HP-PRRSV GSWW15 and the North
American strain FL-12 in infected porcine alveolar macrophages (PAMs) at 12 and
24 hours post-infection. We predicted 12,867 novel lncRNAs, 299 of which were
differentially expressed after viral infection. The Gene Ontology (GO) and Kyoto
Encyclopaedia of Genes and Genomes (KEGG) analyses of the genes adjacent to
lncRNAs showed that they were enriched in pathways related to viral infection and
immune response, indicating that lncRNAs might play regulatory roles in virus
host interactions. Our study provided information about lncRNAs in the porcine
immune system and offers new insights into the pathogenic mechanism of PRRSV
infection and novel antiviral therapy development.
PMID- 28694522
TI - Strong magnetic field effect on the nucleation of a highly undercooled Co-Sn
melt.
AB - High magnetic field is a powerful tool to tune the microstructure and improve the
properties of materials. In this report, the nucleation behavior of undercooled
Co76Sn24 near eutectic alloy under strong homogeneous and gradient magnetic
fields have been investigated using glass slag fluxing method in a 12 T
superconducting magnet. The mean undercooling of the undercooled melt is not
altered by homogeneous magnetic field but depressed by gradient magnetic field.
The highest temperature during recalescence is strongly altered by magnetic
field, where an enhancement effect is observed under gradient magnetic field and
an opposite effect in homogeneous magnetic field. The reason is interpreted by
discussion about the magnetic field on the thermodynamics of nucleation and also
the purifying effect of the glass slag, the magnetic properties and the magnetic
force exerted on the undercooled melt.
PMID- 28694523
TI - Visualizing changes in brain-derived neurotrophic factor (BDNF) expression using
bioluminescence imaging in living mice.
AB - Brain-derived neurotrophic factor (BDNF) plays a fundamental role in expressing
various neural functions including memory consolidation. Alterations of BDNF
levels in the brain are associated with neurodegenerative and neuropsychiatric
disorders. Therefore, it is important to understand how levels of BDNF are
controlled. Recently we generated a novel transgenic mouse strain, termed the
Bdnf-Luciferase transgenic (Bdnf-Luc Tg) mouse, to monitor changes in Bdnf
expression. In the present study, we detected the bioluminescence signal from
living Bdnf-Luc Tg mice after intraperitoneal administration of d-luciferin.
Despite high levels of Bdnf expression in the brain, it was difficult to detect a
signal from the brain region, probably because of its poorly penetrable (short
wavelength) bioluminescence. However, we could detect the changes in the
bioluminescence signal in the brain region using a luciferin analogue generating
a near-infrared wavelength of bioluminescence. We also found a strong correlation
between increases in body weight and bioluminescence signal in the abdominal
region of Tg mice fed a high-fat diet. These results show that changes in Bdnf
expression can be visualized using living mice, and that the Tg mouse could be a
powerful tool for clarification of the role of Bdnf expression in
pathophysiological and physiological conditions.
PMID- 28694524
TI - Prevalence of overweight and obesity in 15.8 million men aged 15-49 years in
rural China from 2010 to 2014.
AB - Obesity has been increasing worldwide. Data on obesity status among men of
reproductive age are scarce. This study aimed to assess the national prevalence
and trend of overweight and obesity among reproductive-age men in rural China. In
the nationwide population-based study, data were obtained from the National Free
Preconception Health Examination Project in rural China from 2010 to 2014. Weight
and height were measured in 16 161 982 men aged 15-49 years and their female
partners (15 997 739 participants aged 15-49 years) before conception, and body
mass index (BMI) was calculated. We found that the prevalence of combined
overweight and obesity among men was 33.8% (33.7-33.9%) according to Chinese
criteria (BMI >= 24.0 kg/m2), the corresponding rates of obesity were 6.3% (6.2
6.4%; BMI >= 28.0 kg/m2), respectively. The prevalence varied in different ethnic
groups, geographic regions, age, education and GDP levels, and increasing trend
was observed over the 5-year study period. In addition, 45.8% of couples had at
least one of them as overweight or obesity. About one third of men aged 15-49
years before conception in rural China are overweight or obese.
Overweight/obesity clusters in families, which highlights the importance of
family involvement of early prevention of obesity in China.
PMID- 28694525
TI - Experimental studies of vibrational modes in a two-dimensional amorphous solid.
AB - The boson peak, which represents an excess of vibrational states compared to
Debye's prediction at low frequencies, has been studied extensively, and yet, its
nature remains controversial. In this study, we focus on understanding the nature
of the boson peak based on the spatial heterogeneity of modulus fluctuations
using a simple model system of a highly jammed two-dimensional granular material.
Despite the simplicity of our system, we find that the boson peak in our two
dimensional system shows a shape very similar to that of three-dimensional
molecular glasses when approaching their boson peak frequencies. Our finding
indicates a strong connection between the boson peak and the spatial
heterogeneity of shear modulus fluctuations.The low-frequency collective
vibrational modes, known as the boson peak, characterize many glasses at low
temperature, yet its origin remains elusive. Zhang et al. show a correlation
between the boson peak and the spatial heterogeneity of shear modulus fluctuation
in a two-dimensional granular system.
PMID- 28694526
TI - Intrapatient functional clonality deconvoluted by coupling intracellular flow
cytometry and next-generation sequencing in human leukemia.
AB - The interplay between tumor heterogeneity and microenvironmental factors is a
critical mechanism for clonal selection in leukemia. Evidence of unique clonal
capacities to engraft within patient-derived xenograft (PDX) models suggests that
intrapatient genetic architecture may be defined by functional differences at the
clonal level. However, methods to detect functional differences assigned to
genetically defined clones remain limited. Here, we describe a scalable method to
directly measure the functional properties of clones within the same leukemia
patient by coupling intracellular flow cytometry and next-generation sequencing
(NGS). We provide proof of concept utilizing primary chronic myelmonocytic
leukemia (CMML) samples and granulocyte-macrophage colony stimulating factor (GM
CSF) to elucidate the interaction between tumor heterogeneity and
microenvironmental factors. Mixtures of human leukemia cell lines, with known
response to GM-CSF, were used to validate the accuracy of our methodology. Using
this approach, we confirm that our method is capable of discriminating GM-CSF
sensitive cell lines, identifies somatic variants in primary leukemia samples,
and resolves functional clonal architecture in an illustrative patient. Taken
together, our data describes a novel method to determine intrapatient functional
clonal heterogeneity and provides proof-of-concept for future investigation aimed
at elucidating the clinical relevance of functional clonal differences.
PMID- 28694527
TI - Revealing enterovirus infection in chronic human disorders: An integrated
diagnostic approach.
AB - Enteroviruses (EVs) causing persisting infection are characterized by minimal
replication and genetic changes. Typing of these agents may complement disease
assessment and shed light on pathogenesis. Here we report an integrated approach
for EV detection in human samples that is based on pre-enrichment of virus in
cell culture before search for the viral genome and viral antigens. Cases of post
polio syndrome, type 1 diabetes, and chronic cardiomyopathy were investigated. As
tissue-based approaches require invasive procedures, information was mainly
gleaned from virus in blood. Molecular assays targeting conserved genome regions
of all EV types (5'UTR, 2 C, 3Dpol) were employed. As compared to direct assays
of plasma or leukocytes, the EV detection rate was significantly enhanced by co
culture of leukocytes with cell lines prior to molecular and immunologic tests.
Results of RT-PCR and sequencing were confirmed by staining cell cultures with a
panel of EV-specific antibodies. Sequence and phylogenetic analysis showed that
EVs of the C species (polioviruses) were associated with the post-polio syndrome,
while members of the B species were found in type 1 diabetes and cardiomyopathy.
The procedure may be used for investigating the possible association of different
EVs with a variety of chronic neurologic, endocrine, and cardiac disorders.
PMID- 28694528
TI - Balancing Hole and Electron Conduction in Ambipolar Split-Gate Thin-Film
Transistors.
AB - Complementary organic electronics is a key enabling technology for the
development of new applications including smart ubiquitous sensors, wearable
electronics, and healthcare devices. High-performance, high-functionality and
reliable complementary circuits require n- and p-type thin-film transistors with
balanced characteristics. Recent advancements in ambipolar organic transistors in
terms of semiconductor and device engineering demonstrate the great potential of
this route but, unfortunately, the actual development of ambipolar organic
complementary electronics is currently hampered by the uneven electron (n-type)
and hole (p-type) conduction in ambipolar organic transistors. Here we show
ambipolar organic thin-film transistors with balanced n-type and p-type
operation. By manipulating air exposure and vacuum annealing conditions, we show
that well-balanced electron and hole transport properties can be easily obtained.
The method is used to control hole and electron conductions in split-gate
transistors based on a solution-processed donor-acceptor semiconducting polymer.
Complementary logic inverters with balanced charging and discharging
characteristics are demonstrated. These findings may open up new opportunities
for the rational design of complementary electronics based on ambipolar organic
transistors.
PMID- 28694529
TI - The production of fibroblast growth factor 23 is controlled by TGF-beta2.
AB - Transforming growth factor-beta (TGF-beta) is a cytokine produced by many cell
types and implicated in cell growth, differentiation, apoptosis, and
inflammation. It stimulates store-operated calcium entry (SOCE) through the
calcium release-activated calcium (CRAC) channel Orai1/Stim1 in endometrial
Ishikawa cells. Bone cells generate fibroblast growth factor (FGF) 23, which
inhibits renal phosphate reabsorption and 1,25(OH)2D3 formation in concert with
its co-receptor Klotho. Moreover, Klotho and FGF23 counteract aging and age
related clinical conditions. FGF23 production is dependent on Orai1-mediated SOCE
and inflammation. Here, we explored a putative role of TGF-beta2 in FGF23
synthesis. To this end, UMR106 osteoblast-like cells were cultured, Fgf23
transcript levels determined by qRT-PCR, FGF23 protein measured by ELISA, and
SOCE analyzed by fluorescence optics. UMR106 cells expressed TGF-beta receptors 1
and 2. TGF-beta2 enhanced SOCE and potently stimulated the production of FGF23,
an effect significantly attenuated by SB431542, an inhibitor of the transforming
growth factor-beta (TGF-beta) type I receptor activin receptor-like kinases ALK5,
ALK4, and ALK7. Furthermore, the TGF-beta2 effect on FGF23 production was blunted
by SOCE inhibitor 2-APB. We conclude that TGF-beta2 induces FGF23 production, an
effect involving up-regulation of SOCE.
PMID- 28694530
TI - Transcriptomic profiling of hemp bast fibres at different developmental stages.
AB - Bast fibres are long extraxylary cells which mechanically support the phloem and
they are divided into xylan- and gelatinous-type, depending on the composition of
their secondary cell walls. The former, typical of jute/kenaf bast fibres, are
characterized by the presence of xylan and a high degree of lignification, while
the latter, found in tension wood, as well as flax, ramie and hemp bast fibres,
have a high abundance of crystalline cellulose. During their differentiation,
bast fibres undergo specific developmental stages: the cells initially elongate
rapidly by intrusive growth, subsequently they cease elongation and start to
thicken. The goal of the present study is to provide a transcriptomic close-up of
the key events accompanying bast fibre development in textile hemp (Cannabis
sativa L.), a fibre crop of great importance. Bast fibres have been sampled from
different stem regions. The developmental stages corresponding to active
elongation and cell wall thickening have been studied using RNA-Seq. The results
show that the fibres sampled at each stem region are characterized by a specific
transcriptomic signature and that the major changes in cell wall-related
processes take place at the internode containing the snap point. The data
generated also identify several interesting candidates for future functional
analysis.
PMID- 28694531
TI - High throughput sequencing of RNA transcriptomes in Ruditapes philippinarum
identifies genes involved in osmotic stress response.
AB - Ruditapes philippinarum, is an economically important marine bivalve species. The
ability to cope with low salinity stress is quite important for the survival of
aquatic species under natural conditions. In this study, the transcriptional
response of the Manila clam to low salinity stress was characterized using RNA
sequencing. The transcriptomes of a low salinity-treatment group (FRp1, FRp2),
which survived under low salinity stress, and control group (SRp1, SRp2), which
was not subjected to low salinity stress, were sequenced with the Illumina HiSeq
platform. A total of 196,578 unigenes were generated. GO and KEGG analyses
revealed that signal transduction, immune response, cellular component
organization or biogenesis, and energy production processes were the most highly
enriched pathways among the genes that were differentially expressed under low
salinity stress. All these pathways could be assigned to the following biological
functions in the low salinity tolerant Manila clam: signal response to low
salinity stress, antioxidant response, intracellular free amino acid transport
and metabolism, energy production and conversion, cell signaling pathways, and
regulation of ionic content and cell volume. In summary, this is the first study
using high-throughput sequencing to identify gene targets that could explain
osmotic regulation mechanisms under salinity stress in R. philippinarum.
PMID- 28694533
TI - If you pluck out the heart of the flax bush, from whence will the bellbird sing?
PMID- 28694532
TI - Membrane Association Landscape of Myelin Basic Protein Portrays Formation of the
Myelin Major Dense Line.
AB - Compact myelin comprises most of the dry weight of myelin, and its insulative
nature is the basis for saltatory conduction of nerve impulses. The major dense
line (MDL) is a 3-nm compartment between two cytoplasmic leaflets of stacked
myelin membranes, mostly occupied by a myelin basic protein (MBP) phase. MBP is
an abundant myelin protein involved in demyelinating diseases, such as multiple
sclerosis. The association of MBP with lipid membranes has been studied for
decades, but the MBP-driven formation of the MDL remains elusive at the
biomolecular level. We employed complementary biophysical methods, including
atomic force microscopy, cryo-electron microscopy, and neutron scattering, to
investigate the formation of membrane stacks all the way from MBP binding onto a
single membrane leaflet to the organisation of a stable MDL. Our results support
the formation of an amorphous protein phase of MBP between two membrane bilayers
and provide a molecular model for MDL formation during myelination, which is of
importance when understanding myelin assembly and demyelinating conditions.
PMID- 28694534
TI - Successful publication by medical students in New Zealand: the role of clinical
versus academic supervisors.
AB - AIM: Relatively little is known about factors that influence successful research
publication by medical students. We aimed to examine the impact of having a
clinical supervisor (compared with full-time academic supervisors) on publication
rates of Bachelor of Medical Sciences (BMedSc(Hons)) theses at the University of
Otago Medical School. METHOD: A secondary analysis of an existing dataset was
conducted. Publications from undergraduate medical theses were previously
identified using standardised criteria. Degree grade was obtained using a
publicly available local search database. RESULTS: Over a 10-year period (2002
2011), 36 (40.4%) out of 89 accepted theses resulted in 55 publications in peer
reviewed journals. There was a total of 137 supervisors (median 1 supervisor per
student, range 1-3), 32.1% of whom were clinical supervisors (n=44). There were
no statistically significant differences in the number of publications (P=0.10)
or degree grades (P=0.49) between students who were supervised by clinical
supervisors and those who were not. CONCLUSION: Clinical supervisors appear just
as effective as full-time researchers in supervising medical students undertaking
an intercalated degree in terms of degree grade and research output. Future
research should focus on examining the association between clinical supervisors
and publication rates from other curricular and extra-curricular research
projects, and focus on reasons behind our observed association.
PMID- 28694535
TI - The role of acromioplasty when repairing rotator cuff tears-no difference in pain
or functional outcome at 24 months in a cohort of 2,441 patients.
AB - AIM: The role of acromioplasty with rotator cuff repair remains unclear. This
study aims to test the null hypothesis-that acromioplasty in conjunction with
rotator cuff repair has no effect on improvement in pain or shoulder function at
two years follow up. METHODS: Data was obtained from a collaborative nationwide
project between March 2009 and December 2010, and consisted of a total of 2,441
patients undergoing primary repair of superior rotator cuff tears. Multivariate
analysis was performed to assess the effect of the inclusion of acromioplasty at
the time of rotator cuff repair on visual analogue scale (VAS) pain scores and
Flex Shoulder Function (Flex SF) scores at 24-month follow up. RESULTS: On
univariate analysis there was a significantly higher Flex SF score in the
acromioplasty group (40.5) compared to the no acromioplasty group (38.7) and a
lower mean pain score at 24 months in the acromioplasty group (1.44 vs 1.74).
There was a significant difference in tear area and surgical repair technique
between the two groups. On multivariate analysis there was no statistically
significant difference in Flex SF or VAS pain scores between the two groups.
CONCLUSION: There was no difference in pain or function scores at two years
following rotator cuff repair regardless of whether or not acromioplasty was
performed. This paper represents the largest study to date comparing
acromioplasty to no acromioplasty in the setting of cuff repair. It supports
previous literature in showing no significant difference in pain or shoulder
function between the two groups.
PMID- 28694536
TI - Orbital fractures treated in Auckland from 2010-2015: review of patient outcomes.
AB - AIM: The purpose of this study was to review patient outcomes from surgical
reconstruction of isolated orbital fractures, performed by the Auckland District
Health Board (ADHB) Oral and Maxillofacial Surgery service (OMFS), from 2010 to
2015. In particular, we wished to assess titanium as an orbital reconstructive
material and compare outcomes with the international literature. METHOD: Hospital
records for 103 adults (>18 years old) who underwent repair of isolated orbital
fractures by the OMFS department at Middlemore Hospital, between 2010 and 2015,
were reviewed. Information collected included patient characteristics, cause of
injury, type of reconstruction material used and post-operative complications.
Patients were then followed up by means of a verbal telephone questionnaire.
RESULTS: The majority of patients were male in the 18-30 year age group, with
interpersonal violence being the leading cause of injury. Titanium was the
preferred choice of reconstructive material. Seven patients required return to
theatre to resolve post-operative complications. Sixty-four patients could be
contacted by telephone (12 months to six years follow-up). Thirty patients, who
could not be contacted by telephone, did attend clinic follow-up and were
assessed from their hospital records (minimum of one month follow-up). Ten
patients could not be contacted by telephone and had not attended clinic follow
up. Problems with diplopia, paraesthesia and cosmesis were within complication
rates reported in the literature. CONCLUSION: Patients with isolated orbital
fractures, treated by the Oral and Maxillofacial Surgery Department in Auckland
from 2010-2015, were reviewed. Titanium was the most commonly used reconstructive
material and proved to be well tolerated. Complication rates were within
international norms.
PMID- 28694537
TI - Survey of antimicrobial stewardship practices in public hospitals in New Zealand
district health boards.
AB - AIMS: To determine what antimicrobial stewardship (AMS) practices exist in New
Zealand public hospitals. METHODS: A quantitative survey based on recommended
components of hospital AMS programmes was sent to the 20 DHBs in June 2016.
RESULTS: Ten of the 20 DHBs had an AMS committee, nine had dedicated AMS
pharmacist full-time equivalents (FTEs) and eight had lead clinician FTEs. Only
one DHB met FTE recommendations for AMS pharmacists and two for clinicians (0.3
and 0.1 FTEs per 100 acute beds, respectively). All DHBs had conducted at least
one antimicrobial audit in the preceding 12 months, most had their own
antimicrobial guidelines (19/20) and prescribing policies (18/20), and 12
reported on antimicrobial usage by at least one metric (eg, defined daily doses).
Staff education on AMS had been given at most DHBs in the previous year, but only
three reported having AMS ward rounds. All DHBs had surveillance programmes for
resistant organisms and most produced antibiograms (16/20). All reported barriers
to implementation of an AMS programme. CONCLUSIONS: Hospital AMS programmes are
in their infancy in New Zealand, with wide variation in practices seen. National
co-ordination is required to assist DHBs in developing effective programmes to
improve antimicrobial use.
PMID- 28694538
TI - Unravelling the whariki of Crown Maori health infrastructure.
AB - New Zealand's central government, and more specifically the Ministry of Health,
consistently acknowledges their special relationship with Maori and the strategic
importance of Maori health, and certainly, strengthening Maori health is critical
to addressing systemic health inequities. This paper, framed in terms of the
Crown principles attributed to the Treaty of Waitangi, ie, participation,
protection and partnership, examines three structural decisions that threaten to
unravel the whariki (foundational mat) of Crown Maori health policy
infrastructure. These include the disestablishment of the Ministry of Health's
policy team, Te Kete Hauora, revoking mandatory district health boards' (DHB)
Maori health plans and reporting, and downscaling the requirements of DHBs to
consult. These actions appear to breach the Articles of te Tiriti o Waitangi and
may be cited as such in the forthcoming WAI 2575 kaupapa health hearing before
the Waitangi Tribunal. The authors call for the Ministry of Health to embrace its
Treaty obligations, and to protect and reinstate the whariki of Maori health
infrastructure.
PMID- 28694539
TI - Visual symptoms and rapid cognitive decline: Heidenhain variant of Creutzfeldt
Jacob Disease.
PMID- 28694540
TI - Adherence to uptake of magnesium sulphate for neuroprotection in preterm births
<30 weeks at Christchurch Hospital.
PMID- 28694541
TI - A cautionary perspective on the utility of the RoPE score in cryptogenic stroke
patients with a patent foramen ovale.
PMID- 28694542
TI - Surveys show exposure to smoking in cars among Year 10 children is not
decreasing: time for the Government to act.
PMID- 28694543
TI - Better organ donation education.
PMID- 28694544
TI - Screening for sub-clinical stress cardiomyopathy and disaster ultrasound
provision in the Kaikoura earthquake.
PMID- 28694545
TI - Is your mental health covered by your health insurance?
PMID- 28694546
TI - Ear candling action overdue.
PMID- 28694547
TI - The Cardiovascular Health of Young Adults: Disparities along the Urban-Rural
Continuum.
AB - U.S. young adults coming of age in the early 21st Century are the first cohort to
grow up during the obesity epidemic; justifiably, there is much concern about
their cardiovascular health. To date, however, no research has examined the
extent to which there are disparities in young adult cardiovascular health across
the urban-rural continuum. We examine this topic using data from the National
Longitudinal Study of Adolescent to Adult Health. We find that young adults who
live in metropolitan core areas exhibit more favorable cardiovascular health than
individuals who live in smaller types of communities, and that population density
largely accounts for this association. Further, individuals living in more
densely populated areas in young adulthood relative to adolescence have better
cardiovascular health than those who live in areas similar or less dense than
their adolescent residence. Our results strongly suggest that the physical and
social features of communities represent important contexts for young adult
cardiovascular health.
PMID- 28694548
TI - Exposure of few layer graphene to Limnodrilus hoffmeisteri modifies the graphene
and changes its bioaccumulation by other organisms.
AB - While graphene has substantial commercial promise, numerous aspects regarding its
ecological effects such as its potential for bioaccumulation are not well known.
14C-labeled few layer graphene (FLG) was dispersed in artificial freshwater and
uptake of FLG by Limnodrilus hoffmeisteri, an oligochaete, was assessed. After
exposure for 36 h to a 1 mg/L FLG suspension, the FLG body burden in the organism
was nearly 60 ng/mg (on a dry mass basis). Multiple characterization results
confirmed that the proteins secreted by the organisms during the exposure period
coated the FLG, thus increasing its stability and decreasing its size in
suspension. Uptake behaviors of Eisenia foetida exposed to FLG and protein-coated
FLG at concentrations of approximately 1 mg/kg or to Daphnia magna at 100 MUg/L
were also quantified. Protein-coated FLG demonstrated different bioaccumulation
behaviors for both organisms compared to uncoated FLG, with the FLG body burden
in E. foetida increased but that in D. magna reduced. The data provide the first
evidence that the proteins secreted by Limnodrilus hoffmeisteri after exposure to
FLG can coat FLG, thus increasing the aqueous stability of FLG, decreasing its
size, and changing its bioaccumulation potential.
PMID- 28694549
TI - LONGITUDINAL EVIDENCE FOR A MIDLIFE NADIR IN HUMAN WELL-BEING: RESULTS FROM FOUR
DATA SETS.
AB - There is a large amount of cross-sectional evidence for a midlife low in the life
cycle of human happiness and well-being (a 'U shape'). Yet no genuinely
longitudinal inquiry has uncovered evidence for a U-shaped pattern. Thus, some
researchers believe the U is a statistical artefact. We re-examine this
fundamental cross-disciplinary question. We suggest a new test. Drawing on four
data sets, and only within-person changes in well-being, we document powerful
support for a U shape in longitudinal data (without the need for formal
regression equations). The article's methodological contribution is to use the
first-derivative properties of a well-being equation.
PMID- 28694550
TI - Children's Experiences of Time when a Parent Travels for Work.
AB - This qualitative study focuses on different ways time is experienced by children
in families who face time challenges due to a family member's job that required
work travel. Data are from a family-level study that includes interviews of all
family members over the age of 7. Using grounded theory methodology, this study
illustrates ways in which job demands and family processes interact. Analysis
centers on the 75 children's perspectives from 43 families. Holding together
assessments of having enough time while wanting more time with their parents,
children express emotion, generally unrecognized by parents, around the topic of
family time. Children's experience of time with parents is rushed or calm,
depending on the activities done in time and the gender of the parent with whom
they spend time. Findings are interpreted through a feminist social
constructionist lens.
PMID- 28694551
TI - Aryne cycloaddition reactions of benzodioxasilines as aryne precursors generated
by catalytic reductive ortho-C-H silylation of phenols with traceless acetal
directing groups.
AB - Diversely substituted arylsilyl triflates, as aryne precursors for aryne
cycloaddition reactions, were accessed from benzodioxasilines. Catalytic
reductive C-H ortho-silylation of phenols with traceless acetal directing groups
was exploited to prepare benzodioxasilines. Sequential addition of MeLi and then
trifluoromethanesulfonic anhydride to benzodioxasilines provided arylsilyl
triflates in a single pot. Notably, this approach was successfully utilized to
prepare sterically hindered 1,2,3-trisubstituted arylsilyl triflates, which
ultimately underwent fluoride-mediated aryne cycloaddition.
PMID- 28694552
TI - Semiparametric modeling and estimation of the terminal behavior of recurrent
marker processes before failure events.
AB - Recurrent event processes with marker measurements are mostly and largely studied
with forward time models starting from an initial event. Interestingly, the
processes could exhibit important terminal behavior during a time period before
occurrence of the failure event. A natural and direct way to study recurrent
events prior to a failure event is to align the processes using the failure event
as the time origin and to examine the terminal behavior by a backward time model.
This paper studies regression models for backward recurrent marker processes by
counting time backward from the failure event. A three-level semiparametric
regression model is proposed for jointly modeling the time to a failure event,
the backward recurrent event process, and the marker observed at the time of each
backward recurrent event. The first level is a proportional hazards model for the
failure time, the second level is a proportional rate model for the recurrent
events occurring before the failure event, and the third level is a proportional
mean model for the marker given the occurrence of a recurrent event backward in
time. By jointly modeling the three components, estimating equations can be
constructed for marked counting processes to estimate the target parameters in
the three-level regression models. Large sample properties of the proposed
estimators are studied and established. The proposed models and methods are
illustrated by a community-based AIDS clinical trial to examine the terminal
behavior of frequencies and severities of opportunistic infections among HIV
infected individuals in the last six months of life.
PMID- 28694553
TI - A scoring metric for multivariate data for reproducibility analysis using
chemometric methods.
AB - Process quality control and reproducibility in emerging measurement fields such
as metabolomics is normally assured by interlaboratory comparison testing. As a
part of this testing process, spectral features from a spectroscopic method such
as nuclear magnetic resonance (NMR) spectroscopy are attributed to particular
analytes within a mixture, and it is the metabolite concentrations that are
returned for comparison between laboratories. However, data quality may also be
assessed directly by using binned spectral data before the time-consuming
identification and quantification. Use of the binned spectra has some advantages,
including preserving information about trace constituents and enabling
identification of process difficulties. In this paper, we demonstrate the use of
binned NMR spectra to conduct a detailed interlaboratory comparison and
composition analysis. Spectra of synthetic and biologically-obtained metabolite
mixtures, taken from a previous interlaboratory study, are compared with cluster
analysis using a variety of distance and entropy metrics. The individual
measurements are then evaluated based on where they fall within their clusters,
and a laboratory-level scoring metric is developed, which provides an assessment
of each laboratory's individual performance.
PMID- 28694554
TI - The Psychosocial Implications of Managing Work and Family Caregiving Roles:
Gender Differences Among Information Technology Professionals.
AB - An increasing number of adults, both men and women, are simultaneously managing
work and family caregiving roles. Guided by the stress process model, we
investigate whether 823 employees occupying diverse family caregiving roles
(child caregiving only, elder caregiving only, and both child caregiving and
elder caregiving, or "sandwiched" caregiving) and their noncaregiving
counterparts in the information technology division of a white-collar
organization differ on several indicators of psychosocial stress along with
gender differences in stress exposure. Compared with noncaregivers, child
caregivers reported more perceived stress and partner strain whereas elder
caregivers reported greater perceived stress and psychological distress. With the
exception of work-to-family conflict, sandwiched caregivers reported poorer
overall psychosocial functioning. Additionally, sandwiched women reported more
family-to-work conflict and less partner support than their male counterparts.
Further research on the implications of combining a white-collar employment role
with different family caregiving roles is warranted.
PMID- 28694555
TI - Parental Leave Use among Disadvantaged Fathers.
AB - The United States lags behind other industrialized countries in its lack of
inclusive and standardized parental leave policy after the birth or adoption of a
child. Using data from the Fragile Families and Child Wellbeing Study (N=2,233),
this study examines the patterns and predictors of fathers' parental leave use,
as well as its association with father-child engagement. Our findings indicate
that the vast majority of employed fathers take parental leave, but they rarely
take more than one week of leave. Fathers who have more positive attitudes about
fatherhood and who live with the birth mother are especially likely to take
leave, and to take more weeks of leave, than other fathers. Finally, we find that
taking parental leave, and taking more weeks of parental leave, is positively
associated with father engagement levels at one year and five years after the
birth of his child.
PMID- 28694556
TI - Fertility after natural disaster: Hurricane Mitch in Nicaragua.
AB - This investigation evaluates the effect of Hurricane Mitch on women's
reproductive outcomes throughout Nicaragua. This research aim is achieved by
analyzing a unique Nicaraguan Living Standards Measurement Study panel dataset
that tracks women's fertility immediately before and at two time points after
Hurricane Mitch, combined with satellite-derived municipality-level precipitation
data for the 10-day storm period. Results show higher odds of post-disaster
fertility in municipalities receiving higher precipitation levels in the
immediate post-Hurricane Mitch period. However, fertility normalizes between
disaster and non-disaster areas four to six years after the storm. These findings
suggest that the disruptive effects of a natural disaster such as Hurricane Mitch
can have an initial stimulative effect on fertility but the effect is ephemeral.
PMID- 28694557
TI - Overexpression of miR-24 Is Involved in the Formation of Hypocoagulation State
after Severe Trauma by Inhibiting the Synthesis of Coagulation Factor X.
AB - BACKGROUND: Dysregulation of microRNAs may contribute to the progression of
trauma-induced coagulopathy (TIC). We aimed to explore the biological function
that miRNA-24-3p (miR-24) might have in coagulation factor deficiency after major
trauma and TIC. METHODS: 15 healthy volunteers and 36 severe trauma patients
(Injury Severity Score >= 16 were enrolled. TIC was determined as the initial
international normalized ratio >1.5. The miR-24 expression and concentrations of
factor X (FX) and factor XII in plasma were measured. In vitro study was
conducted on L02 cell line. RESULTS: The plasma miR-24 expression was
significantly elevated by 3.17-fold (P = 0.043) in major trauma patients and
reduced after 3 days (P < 0.01). The expression level was significantly higher in
TIC than in non-TIC patients (P = 0.040). Multivariate analysis showed that the
higher miR-24 expression was associated with TIC. The plasma concentration of FX
in TIC patients was significantly lower than in the non-TIC ones (P = 0.030) and
controls (P < 0.01). A negative correlation was observed between miR-24 and FX.
miR-24 transduction significantly reduced the FX level in the supernatant of L02
cells (P = 0.030). CONCLUSIONS: miR-24 was overexpressed in major trauma and TIC
patients. The negative correlation of miR-24 with FX suggested the possibility
that miR-24 might inhibit the synthesis of FX during TIC.
PMID- 28694558
TI - Impact of Vaccination on Distribution of T Cell Subsets in Antiretroviral-Treated
HIV-Infected Children.
AB - Antiretroviral therapy (ART) is generally prescribed to patients with human
immunodeficiency virus (HIV) infection with vaccination introduced to prevent
disease complications. However, little is known about the influence of
immunization on T cell subsets' distribution during the course of infection. This
study aims to identify the impact of viral replication and immunization on naive,
effector, effector memory, and central memory T cell subpopulations in ART
treated HIV-infected children. Fifty patients were recruited and injected
intramuscularly with influenza A (H1N1) 2009 vaccine on the day of enrollment
(day 0) and day 28. Blood samples were collected for pre- and postvaccination on
days 0 and 56 for analyzing T cell phenotypes by flow cytometry. Phenotypes of
all T cell subsets remained the same after vaccination, except for a reduction in
effector CD8+ T cells. Moreover, T cell subsets from patients with controllable
viral load showed similar patterns to those with virological failure. Absolute
CD4 count was also found to have a positive relationship with naive CD4+ and CD8+
T cells. In conclusion, vaccination and viral replication have a little effect on
the distribution of T cell subpopulations. The CD4 count can be used for
prediction of naive T cell level in HIV-infected patients responding to ART.
PMID- 28694559
TI - Association of Single-Nucleotide Polymorphisms in DC-SIGN with Nasopharyngeal
Carcinoma Susceptibility.
AB - The aim of this study was to explore potential relationships of four single
nucleotide polymorphisms (SNPs) in the gene encoding dendritic cell-specific
intercellular adhesion molecule 3-grabbing nonintegrin (DC-SIGN) with risk of
nasopharyngeal carcinoma (NPC). The DC-SIGN SNPs rs7252229, rs4804803, rs2287886,
and rs735240 were genotyped in 477 unrelated NPC patients and 561 cancer-free
controls. At rs7252229, risk of NPC was significantly lower in individuals with
GC (odds ratio [OR] 0.076, 95% confidence interval [CI] 0.008-0.690), GG (OR
0.056, 95%CI 0.006-0.487), or GC + GG (OR 0.059, 95%CI 0.007-0.515) than in
individuals with the CC genotype, after adjusting for age, gender, smoking
history, and EBV-VCA-IgA status. At rs4804803, risk of NPC was significantly
higher in individuals with the genotype GG than in those with the genotype AA
(adjusted OR 9.038, 95%CI 1.708-47.822). At rs735240, risk of NPC did not change
significantly with genotypes AG, GG, or AG + GG after adjusting for age, gender,
and smoking history. However, when data were also adjusted for EBV-VCA-IgA
status, three genotypes emerged as associated with significantly higher risk of
NPC than the AA genotype: AG (OR 2.976, 95%CI 1.123-7.888), GG (OR 3.314, 95%CI
1.274-8.622), or GG + AG (OR 3.191, 95%CI 1.237-8.230). Our results suggest that
DC-SIGN SNPs rs7252229, rs4804803, and rs735240 may influence NPC risk in the
Chinese population. The mechanisms mediating this risk require a further study.
PMID- 28694560
TI - Peritransplant Soluble CD30 as a Risk Factor for Slow Kidney Allograft Function,
Early Acute Rejection, Worse Long-Term Allograft Function, and Patients'
Survival.
AB - BACKGROUND: We aimed to determine whether serum soluble CD30 (sCD30) could
identify recipients at high risk for unfavorable early and late kidney transplant
outcomes. METHODS: Serum sCD30 was measured on the day of kidney transplantation
and on the 4th day posttransplant. We assessed the value of these measurements in
predicting delayed graft function, slow graft function (SGF), acute rejection
(AR), pyelonephritis, decline of allograft function after 6 months, and graft and
patient survival during 5 years of follow-up in 45 recipients. RESULTS: We found
the association between low pretransplant serum levels of sCD30 and SGF. The
absence of significant decrease of sCD30 on the 4th day posttransplant was
characteristic for SGF, early AR (the 8th day-6 months), late AR (>6 months), and
early pyelonephritis (the 8th day-2 months). Lower pretransplant and
posttransplant sCD30 predicted worse allograft function at 6 months and 2 years,
respectively. Higher pretransplant sCD30 was associated with higher frequency of
early AR, and worse patients' survival, but only in the recipients of deceased
donor graft. Pretransplant sCD30 also allowed to differentiate patients with
early pyelonephritis and early AR. CONCLUSIONS: Peritransplant sCD30 is useful in
identifying patients at risk for unfavorable early and late transplant outcomes.
PMID- 28694561
TI - Socioeconomic Inequalities in Health in China: A Reassessment with Data from the
2010-2012 China Family Panel Studies.
PMID- 28694562
TI - Expression and Function of Granzymes A and B in Escherichia coli Peritonitis and
Sepsis.
AB - Escherichia (E.) coli is the most common causative pathogen in peritonitis, the
second most common cause of sepsis. Granzymes (gzms) are serine proteases
traditionally implicated in cytotoxicity and, more recently, in the inflammatory
response. We here sought to investigate the role of gzms in the host response to
E. coli-induced peritonitis and sepsis in vivo. For this purpose, we used a
murine model of E. coli intraperitoneal infection, resembling the clinical
condition commonly associated with septic peritonitis by this bacterium, in wild
type and gzmA-deficient (gzmA-/- ), gzmB-/- , and gzmAxB-/- mice. GzmA and gzmB
were predominantly expressed by natural killer cells, and during abdominal
sepsis, the percentage of these cells expressing gzms in peritoneal lavage fluid
decreased, while the amount of expression in the gzm+ cells increased. Deficiency
of gzmA and/or gzmB was associated with increased bacterial loads, especially in
the case of gzmB at the primary site of infection at late stage sepsis. While gzm
deficiency did not impact neutrophil recruitment into the abdominal cavity, it
was accompanied by enhanced nucleosome release at the primary site of infection,
earlier hepatic necrosis, and more renal dysfunction. These results suggest that
gzms influence bacterial growth and the host inflammatory response during
abdominal sepsis caused by E. coli.
PMID- 28694563
TI - Role of ARPC2 in Human Gastric Cancer.
AB - Gastric cancer continues to be the second most frequent cause of cancer deaths
worldwide. However, the exact molecular mechanisms are still unclear. Further
research to find potential targets for therapy is critical and urgent. In this
study, we found that ARPC2 promoted cell proliferation and invasion in the human
cancer cell line MKN-28 using a cell total number assay, MTT (3-(4,5-dimethyl-2
thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide) assay, cell colony formation
assay, migration assay, invasion assay, and wound healing assay. For downstream
pathways, CTNND1, EZH2, BCL2L2, CDH2, VIM, and EGFR were upregulated by ARPC2,
whereas PTEN, BAK, and CDH1 were downregulated by ARPC2. In a clinical study, we
examined the expression of ARPC2 in 110 cases of normal human gastric tissues and
110 cases of human gastric cancer tissues. ARPC2 showed higher expression in
gastric cancer tissues than in normal gastric tissues. In the association
analysis of 110 gastric cancer tissues, ARPC2 showed significant associations
with large tumor size, lymph node invasion, and high tumor stage. In addition,
ARPC2-positive patients exhibited lower RFS and OS rates compared with ARPC2
negative patients. We thus identify that ARPC2 plays an aneretic role in human
gastric cancer and provided a new target for gastric cancer therapy.
PMID- 28694564
TI - HMGB1 and Extracellular Histones Significantly Contribute to Systemic
Inflammation and Multiple Organ Failure in Acute Liver Failure.
AB - Acute liver failure (ALF) is the culmination of severe liver cell injury from a
variety of causes. ALF occurs when the extent of hepatocyte death exceeds the
hepatic regenerative capacity. ALF has a high mortality that is associated with
multiple organ failure (MOF) and sepsis; however, the underlying mechanisms are
still not clear. Emerging evidence shows that ALF patients/animals have high
concentrations of circulating HMGB1, which can contribute to multiple organ
injuries and mediate gut bacterial translocation (BT). BT triggers/induces
systemic inflammatory responses syndrome (SIRS), which can lead to MOF in ALF.
Blockade of HMGB1 significantly decreases BT and improves hepatocyte regeneration
in experimental acute fatal liver injury. Therefore, HMGB1 seems to be an
important factor that links BT and systemic inflammation in ALF. ALF
patients/animals also have high levels of circulating histones, which might be
the major mediators of systemic inflammation in patients with ALF. Extracellular
histones kill endothelial cells and elicit immunostimulatory effect to induce
multiple organ injuries. Neutralization of histones can attenuate acute liver,
lung, and brain injuries. In conclusion, HMGB1 and histones play a significant
role in inducing systemic inflammation and MOF in ALF.
PMID- 28694565
TI - 5-HT Drives Mortality in Sepsis Induced by Cecal Ligation and Puncture in Mice.
AB - Sepsis is defined as a life-threatening organ dysfunction caused by a
dysregulated host response to infection with a high mortality. 5
Hydroxytryptamine (5-HT) is an important regulatory factor in inflammation. The
aim of this study is to investigate the role of 5-HT on cecal ligation and
puncture- (CLP-) induced sepsis in the mouse model. CLP was performed on C57B/6
wild-type (WT) mice and tryptophan hydroxylase 1 (TPH1) knockout (KO) mice. The
results showed that the 5-HT-sufficient group mice had a significantly lower
survival rate than the 5-HT-deficient group in CLP-induced sepsis and septic
shock. The KO-CLP sepsis group received a lower clinical score than the WT-CLP
sepsis group. Meanwhile, the body temperature of mice in the KO-CLP sepsis group
was higher than that in the WT-CLP sepsis group and was much closer to the normal
body temperature 24 hours after CLP. The tissue histopathology analysis revealed
that 5-HT markedly exacerbated histological damages in the peritoneum, lung,
liver, kidney, intestinal tissue, and heart in sepsis. Moreover, significant
lower levels of TNF-alpha, IL-6, bacterial loads, MPO, and ROS were discovered in
the KO-CLP sepsis group in contrast to the WT-CLP sepsis group. In conclusion, 5
HT drives mortality and exacerbates organ dysfunction by promoting serum
cytokines and bacterial loads as well as facilitating oxidative stress in the
process of sepsis.
PMID- 28694567
TI - Immunohistochemistry in Ureteropelvic Junction Obstruction and Its Correlation to
Postoperative Outcome.
AB - AIM: To investigate the correlation between the status of interstitial cells of
Cajal (ICC) in ureteropelvic junction (UPJ) and the resected ureteric margin and
the postoperative outcome of Anderson-Hynes pyeloplasty in UPJ obstruction (UPJO)
and to compare the ICC in the UPJ and the resected margin of the normal ureter.
MATERIALS AND METHODS: An observational study was conducted over a period of 2
years at the Department of Pediatric Surgery at Niloufer Institute of Women and
Child Health. Children with intrinsic UPJO who underwent Anderson-Hynes
dismembered pyeloplasty were included in the study. Six months postoperatively,
the patients were divided into two groups based on diuretic isotopic renogram
using technetium-99m-labeled diethylene triaminepentaacetic acid. Group 1
comprised patients with good surgical outcome. Group 2 comprised patients with a
poor outcome. The histologic specimens were evaluated for ICC, and the
immunohistochemical findings were correlated with the outcome. RESULTS: Twenty
five patients were included in this study (19 male and 6 female). Seventy-six
percent of patients were under the age of 1 year. Group 1 had 23 cases and Group
2 had 2 cases. Out of the two patients with a poor outcome, one had negative
grading at the UPJ and one had positive grading. Both these patients had a
negative grading at the lower resected margins. More number of patients (24%) had
+++ grading at the lower resected margin when compared to the UPJ (8%).
CONCLUSION: This is the first study which correlates the status of ICC in UPJ
with the outcome of pyeloplasty in pediatric patients. Both the cases with bad
outcome had no ICC at the lower margin of the resected specimen and one case had
no ICC at the UPJ. There is a statistically significant difference (P = 0.001) in
the number of ICC at the UPJ and the resected margin.
PMID- 28694568
TI - The Role of Routine Measurement of Intra-abdominal Pressure in Preventing
Abdominal Compartment Syndrome.
AB - INTRODUCTION: Abdomen, a closed compartment, is prone to raised intra-abdominal
pressure (IAP) in the postoperative period. After a critical value of >= 15 cm of
water, IAP produces abdominal compartment syndrome (ACS). ACS leads to reduced
venous return, reduced cardiac output, and domino effect of organ dysfunction,
leading to death. Hence, it is the need of hour to monitor IAP to pick up intra
abdominal hypertension (IAH) and ACS. This routine facilitates early institution
of treatment measures. AIMS AND OBJECTIVES: To study IAP in abdominal operations
in neonates, infants, and older children and to promote concept of routine
measurement of IAP as standard care. MATERIALS AND METHODS: Intravesical route
was used to measure IAP in this prospective observational study. Seventy-nine
pediatric abdominal surgeries met with criteria of availability of complete data
for analysis and formed the cohort of the study. All major, infective, traumatic,
tumor-related abdominal surgeries were included in the study. Outcome, C-reactive
protein (CRP), procalcitonin, platelet counts, Simplified Sequential Organ
Failure Assessment Score, and Acute Physiology and Chronic Health Evaluation II
(APACHE II) score were the parameters analyzed. The World Society of ACS grading
was adopted in the study with subdivision of normal into low-normal and high
normal subgroups. RESULTS: Extended Mantel-Haenszel Chi-square statistical tool
when applied for linear relationship showed a linear relationship with outcome (P
< 0.05), CRP (P < 0.05), procalcitonin (P < 0.05), Simplified Sequential organ
failure Assessment Score, and APACHE II. Platelet counts (P > 0.05) were not
significantly correlated. Decision for laparotomy was delayed in cases of ACS.
CONCLUSION: Routine measure of IAP facilitates early recognition of IAH. This
facilitates therapeutic measures to be initiated to reduce IAP. Early decision to
decompress by laparotomy/laparostomy saves lives. Hence, routine IAP measurement
should be a part of standard care in pediatric abdominal surgery.
PMID- 28694566
TI - Antifungal Resistance, Metabolic Routes as Drug Targets, and New Antifungal
Agents: An Overview about Endemic Dimorphic Fungi.
AB - Diseases caused by fungi can occur in healthy people, but immunocompromised
patients are the major risk group for invasive fungal infections. Cases of fungal
resistance and the difficulty of treatment make fungal infections a public health
problem. This review explores mechanisms used by fungi to promote fungal
resistance, such as the mutation or overexpression of drug targets, efflux and
degradation systems, and pleiotropic drug responses. Alternative novel drug
targets have been investigated; these include metabolic routes used by fungi
during infection, such as trehalose and amino acid metabolism and mitochondrial
proteins. An overview of new antifungal agents, including nanostructured
antifungals, as well as of repositioning approaches is discussed. Studies
focusing on the development of vaccines against antifungal diseases have
increased in recent years, as these strategies can be applied in combination with
antifungal therapy to prevent posttreatment sequelae. Studies focused on the
development of a pan-fungal vaccine and antifungal drugs can improve the
treatment of immunocompromised patients and reduce treatment costs.
PMID- 28694569
TI - Male Gender and Prematurity are Risk Factors for Incarceration in Pediatric
Inguinal Hernia: A Study of 922 Children.
AB - OBJECTIVES: The purpose of this study was to document clinical features of
inguinal hernia (IH) in the pediatric population. It provides data to evaluate
associated risk factors of incarcerated hernia, its recurrence as well as the
occurrence of contralateral metachronous hernia. MATERIALS AND METHODS: We report
a retrospective analytic study including 922 children presenting with IH and
operated from 2010 to 2013 in our pediatric surgery department. RESULTS: We
managed 143 girls (16%) and 779 boys (84%). The mean age was 2 years; the right
side was predominantly affected (66.8%, n = 616). Incarcerated hernia was
documented in 16% of cases with an incidence of 33% in neonates. The
incarceration occurrence was 15.5% in males versus 2.09% in females. The surgical
repair was done according to Forgue technique. Postoperatively, four cases of
hernia recurrence were documented, and contralateral metachronous hernia was
reported in 33 children with 7.7% females versus 2.8% males. Forty-five percent
of them were infants. The mean follow-up period was 4 years. We think that
incarceration can be related to several risk factors such as feminine gender,
prematurity, and the initial left side surgical repair of the hernia. CONCLUSION:
IH occurs mainly in male infants. Prematurity and male gender were identified as
risk factors of incarceration. Contralateral metachronous hernia was reported,
especially in female infants and after a left side surgical repair of the hernia.
PMID- 28694570
TI - Extrahepatic Portal Vein Obstruction in Children: Role of Preoperative Imaging.
AB - AIM: Extrahepatic portal vein obstruction (EHPVO) is characterized by features of
recent thrombosis or portal hypertension with portal cavernoma as a sequel of
portal vein obstruction. Imaging of spleno-portal axis is the mainstay for the
diagnosis of EHPVO. The aim of this study is to analyze the role of imaging in
the preoperative assessment of the portal venous system in children with EHPVO.
MATERIALS AND METHODS: A hospital-based cross-sectional study was conducted on
twenty children with EHPVO aged between 1 and 18 years over a period of 1 year.
The children were evaluated clinically, followed by upper gastrointestinal
endoscopy. Radiological assessment included imaging of the main portal vein, its
right and left branches, splenic vein, and superior mesenteric vein using color
Doppler ultrasonography (CDUSG) and magnetic resonance portovenogram (MRP).
Evidence of portal biliopathy, status of collaterals, and possible sites for
portosystemic shunt surgery were also examined. RESULTS: All the patients
presented in chronic stage with portal cavernoma and only one patient (5%) had
bland thrombus associated with cavernoma. The CDUSG and MRPs had a sensitivity of
66.6-90% and 96.7% and specificity of 91.5% and 98.3% respectively with regard to
the assessment of the extent of thrombus formation and flow in the portal venous
system. Both the modalities were found to be complementary to each other in
preoperative assessment of EHPVO. However, the sensitivity of MRP was slightly
superior to CDUSG in detecting occlusion and identifying portosystemic
collaterals and dilated intrahepatic biliary radicals. CONCLUSION: Results of the
present study indicate that MRP is well suited and superior to CDUSG in the
preoperative imaging of patients with EHPVO.
PMID- 28694571
TI - Video-Assisted Thoracoscopic Surgery for Pediatric Empyema by Two-Port Technique:
A Single-Center Experience with 167 Consecutive Cases.
AB - BACKGROUND/PURPOSE: The aim of our study is to determine efficacy, safety, and
feasibility of video-assisted thoracoscopic surgery (VATS) in childhood empyema
with a technique of only two ports and open instruments at a tertiary care center
in India. METHODS: This is a retrospective study of patients below 18 years, with
empyema presenting to the Department of Pediatric Surgery of a Tertiary Care
Referral Hospital in India, over a period of 9 years who underwent VATS
decortication. Only two ports with open surgical instruments were used. The
patients were assessed on the basis of mean duration of preoperative symptoms,
duration of surgery, average blood loss, postoperative pain relief,
complications, and need for redo surgery. RESULTS: A total of 97 patients
underwent primary VATS decortications without inserting an intercostal drainage
(ICD) tube and 70 patients as a secondary procedure after ICD tube was inserted.
Mean duration of symptoms was 11 days. The average blood loss during surgery was
estimated to be 170 cc. The mean duration of surgery was 90 min. The most common
postoperative complication was air leak seen in 19.16% of patients. Minor leaks
usually settled by 24 h. In eight patients, a negative suction had to be applied
to the ICD tube for persistent air leak. The average length of postoperative stay
was 4 days. Two patients required a repeat open decortication procedure due to
nonresolution of symptoms and poor lung expansion after VATS. Patients had
minimal pain and excellent cosmetic outcome after VATS. CONCLUSION: Two-port VATS
decortication procedure is as feasible and effective as three-port procedure for
decortication with better cosmetic result and pain relief.
PMID- 28694572
TI - Pediatric Ventriculoperitoneal Shunts and their Complications: An Analysis.
AB - INTRODUCTION: Ventriculoperitoneal (VP) shunt is the most commonly utilized
shunting procedure because of the capacity of the peritoneum to resorb fluid.
Initial and subsequent peritoneal catheter placements can be done with relative
ease. They are associated with a variety of complications. MATERIALS AND METHODS:
The total number of patients operated in the study period was 96. We studied 41
operated patients of VP shunt who had various shunt-related complications and
analyzed the predisposing risk factors and spectrum of complications. RESULTS:
The mean age was 28 +/- 32 months out of which 28 were males and 13 females. The
etiology of hydrocephalus was aqueductal stenosis in 18, Arnold Chiari
malformation in 10, Dandy-Walker malformation in 2, postmeningitis in 8 (pyogenic
in 5 and tubercular in 3), postintraventricular hemorrhage in 2 patients and
postencephalocele surgery in 1. CONCLUSION: With this retrospective review of
complications of VP shunts, age at initial shunt insertion and the interval
between the age of initial shunt placement and onset of complications were the
most important patient-related predictors of shunt failure. The different
predominant etiological factors responsible for early and late shunt failure were
infective and mechanical complications, respectively.
PMID- 28694573
TI - Two Stages Repair of Proximal Hypospadias: Review of 700 Cases.
AB - OBJECTIVE: Surgical repair of hypospadias is challenging and problematic even for
the most experienced specialists, and this is especially true when severe and
complicated case is confronted. Many operations had been described for the
management of this deformity. MATERIALS AND METHODS: During the period from May
2004 to December 2015, we performed 700 cases with proximal hypospadias, at our
institute in the Department of Pediatric Surgery by a single surgeon. Data were
collected retrospectively and included patient's age at operation, degree of the
hypospadias, degree of associated chordee, complications, and cosmetic outcome.
All patients underwent 2 two-stage procedures with 9-12 months interval in
between. RESULTS: Seven hundred patients with proximal hypospadias were operated
upon in a period of 11 years. Byars's 2 two-stage operation was used in all 700
cases. Neither complete disruption nor urethral diverticula occurred 2 two-stage
procedures in the 700 patients. 677 (96.7%) patients had no complication. Fistula
was present in 21 (3%) patients. There was no case of meatal stenosis in our
study. CONCLUSION: Two stages procedure using the principles of Byar's technique
is a versatile operation that can be used for 2 two-stage procedures the proximal
hypospadias. It decreases the rate of fistula formation, disruption, and stenosis
and gives a satisfactory cosmetic appearance.
PMID- 28694574
TI - Clitoral Choristoma: A Rare Case Report.
AB - Clitoral hypertrophy is usually seen as a congenital malformation, specifically
during the stages of hormonal expressions in the disorders of sexual development.
Acquired clitoral hypertrophy is a relatively rare condition. Clitoris can be the
site of neoplastic lesions. Clitoral choristoma has not been reported so far in
the literature.
PMID- 28694575
TI - Early Thoracoscopic Plication of Diaphragm in a Newborn with Brachial Plexus
Palsy and Concurrent Phrenic Nerve Palsy.
AB - Phrenic nerve palsy is a rare cause of respiratory distress in a newborn. When
conservative measures fail to achieve adequate ventilation, then early surgical
plication has been found to be associated with good outcome. We report a case of
neonate with phrenic nerve palsy in whom an early thoracoscopic diaphragmatic
plication was done.
PMID- 28694576
TI - Zollinger-Ellison Syndrome in a 12-year-old Child.
AB - The syndrome described by Zollinger and Ellison in 1955 is a rare clinical entity
which is even rarer in children. This report describes a 12-year-old boy who
presented with refractory peptic ulcer disease which was finally diagnosed to be
due to a gastrinoma and was successfully treated.
PMID- 28694577
TI - Kawasaki Disease Presenting as Acute Intestinal Obstruction.
AB - Kawasaki disease (KD) is an acute febrile illness of childhood associated with
vasculitis of medium-sized arteries especially the coronary arteries. Typical
clinical features involving the skin, mucous surfaces, etc., occur sequentially
over a few days. We report a rare presentation of KD as a surgical abdomen in a 2
year-old boy. Awareness of this presentation is important as it can otherwise
lead to a delay in starting potentially life-saving intervention like intravenous
immunoglobulins for cardiac complications kept cryptic by the manifest acute
abdomen.
PMID- 28694578
TI - Mesenteric Leiomyoma in Infancy.
AB - A 10-year-old female presented with a palpable mass occupying the entire abdomen.
Computerized tomography scan showed a large expansive lesion measuring 22 cm * 20
cm * 13 cm. The mass was resected and the diagnosis of leiomyoma was made from
immunehistochemical findings. Mesenteric leiomyoma is an uncommon tumor among
gastrointestinal stromal tumors.
PMID- 28694579
TI - Surgical Repair of Congenital Abdominal Aortic Aneurysm in a 1-year-old Child
with Literature Review.
AB - Reported here is a case of 1-year-old male child who presented with huge
abdominal mass, which on radiological investigation was diagnosed as
retroperitoneal pseudoaneurysm of the aorta. On exploration, it was found to be a
true aneurysm of infrarenal abdominal aorta with inflow agenesis. Aneurysm was
excised, and aorta was reconstructed with 10 mm Dacron graft. Postoperative
computed tomography angiography showed patent graft with good distal runoff.
Literature review revealed that only 26 cases of congenital abdominal aortic
aneurysm had been reported so far. None of them had inflow agenesis which can
give false impression of pseudoaneurysm on preoperative evaluation. The case
highlights the utility of additional complimentary investigations such as Doppler
study in clinching diagnosis and helping plan and execute successful treatment in
the difficult diagnostic scenario.
PMID- 28694580
TI - A Sharp Lesson: Duodenal Perforation 2 Months after Ingestion of a Pin.
AB - An 11-year-old female child presented 2 months after accidentally swallowing her
hijab pin, with right-sided abdominal pain. An X-ray showed that the pin was
located in her right upper quadrant, and at laparoscopy, it was found to have
eroded through her duodenum into her liver. Ingested pins should always be
removed if not passed spontaneously within the first few days.
PMID- 28694581
TI - Leydig Cell Tumor of Testis in a Child: An Uncommon Presentation.
AB - Leydig cell tumors (LCTs) are rare testicular tumors. Incidence is 1%-3% of all
testicular neoplasms, bilateral in 10%. They are frequently hormonally active,
leading to feminizing or virilizing syndromes. LCTs can be either pure or mixed
with germ cell tumors or other sex cord-stromal tumors. Here, we are reporting a
benign pure LCT in a 6-year-old boy presented with pseudopuberty.
PMID- 28694582
TI - Pleomorphic Lipoma of the Neck in an Infant: A Rare Clinical Entity.
AB - Lipomas are rare in the pediatric age group. A 10-month-old male child presented
with an asymptomatic neck mass which was evaluated and excised completely.
Histopathology was consistent with pleomorphic lipoma, not previously reported in
children.
PMID- 28694583
TI - Simple Technique of Bridging Wide Gap in Esophageal Atresia with
Tracheoesophageal Fistula - "Surgical Innovation".
AB - The survival of the patients with esophageal atresia an tracheo esophageal
fistula is believed to be an epitome of the success of the neonatal surgery.
Restoring the continuty of the food pipe by esophagus to esophagus anastomosis is
the best option. Preservation of natural esophagus by delayed repair in a wide
gap esophageal atresia is a preferred technique worldwide, however such a
management required prolonged hospitalization and dedicated nursing care, which
is often not available in most of the centres in India. Esophageal substitutes in
wide gap requires multiple operations and have long term problems, so remains the
last option. I use the technique of oblique anastomosis which had distrinct
advantage over circular anastomosis in the management of esophageal atresia1.
This techniqe helps in bridging wide gap to some extent & minimal stricture
formation.
PMID- 28694584
TI - Retrocaval Ureter: Clinical Images.
AB - Retrocaval ureter (RCU) is a rare congenital anomaly with the ureter looping
around inferior vena cava (IVC). We present the case of 10-year-old boy.
Diagnosis was confirmed with ultrasound and CT. He underwent retroperitoneoscopic
uretero-ureterostomy.
PMID- 28694585
TI - Delayed Presentation of Congenital Colonic Stenosis.
PMID- 28694586
TI - Duplicate Bladder Exstrophy with Hypospadias: A Rare Exstrophy Variant with
Unusual Association.
PMID- 28694587
TI - Coexistence of Both Bronchogenic and Esophageal Duplication Cyst in a Single
Mass: An Interesting Coincidence.
PMID- 28694588
TI - Is sectioning of muscle attachment to axis (C2) spinous process mandatory to
achieve arthrodesis during atlantoaxial fixation?
PMID- 28694589
TI - Beyond radiological imaging: Direct observation and manual physical evaluation of
spinal instability.
PMID- 28694590
TI - Spinal angiolipomas: A puzzling case and review of a rare entity.
AB - Patients with spinal epidural abscesses (SEAs) may have a variable presentation.
Such an infection has a typical appearance on magnetic resonance imaging (MRI)
and enhances with gadolinium. We present a case that was a diagnostic challenge
where pre- and intra-operative findings resulted in conflicting impressions. The
mimicker was a spinal angiolipoma (SAL). The authors then provide a thorough
review of this rare spinal neoplasm. A 55-year-old man presented with back pain,
paresis, paresthesia, and urinary retention. MRI was indicative of a longitudinal
epidural thoracic mass with a signal homogeneous to nearby fat, curvilinear
vessels, and lack of enhancement. Although at emergent surgery, the lesion was
found to contain abundant purulent material. Microbiology was positive for
methicillin-resistant Staphylococcus aureus and consistent with SEA without
evidence of neoplasia. While the imaging features were suggestive of an
angiolipoma, the findings at surgery made SEA more likely, which were validated
histopathologically. The diagnosis of SEA is often clear-cut, and the literature
has reported only a few instances in which it masqueraded as another process such
as lymphoma or myelitis. The case highlights SEA masquerading as an angiolipoma,
and further demonstrates to clinicians that obtaining tissue diagnosis plays a
crucial role diagnostically and therapeutically. SALs, on the other hand, are
slow-growing tumors that can be infiltrating or noninfiltrating. They typically
present with chronic symptoms and T1-MRI shows an inhomogeneous picture. Complete
surgical excision is standard of care and patients tend to do well afterward.
PMID- 28694591
TI - Atlas instrumentation guided by the medial edge of the posterior arch: An
anatomic and radiologic study.
AB - STUDY DESIGN: This was an interventional human cadaver study and radiological
study. OBJECTIVES: Atlas instrumentation is frequently involved in fusion
procedures involving the craniocervical junction area. Identification of the
entry point at the center of atlas lateral mass (ALM) is challenging because of
its rounded posterior surface and the surrounding venous plexus. This report
examines using the medial edge of atlas posterior arch (MEC1) as a fixed and
reliable anatomic reference to guide the entry point of ALM screws. METHODS:
Fifty, normal, cervical spine computed tomography studies were reviewed. ALM
screw trajectories were planned at one point along MEC1 and another point 2 mm
lateral to MEC1. Free-hand ALM instrumentation was performed in ten fresh human
cadavers using the 2 mm entry point, with a sagittal trajectory parallel to atlas
inferior arch (IAC1); three-dimensional imaging was then performed to confirm
instrumentation accuracy. RESULTS: The average ALM diameter was 12.35 mm.
Inserting a screw using the entry point 2 mm lateral to MEC1 was closer to ALM
midpoint than using the entry point along MEC1 (P < 0.0001). Twenty ALM screws
were successfully inserted in the ten cadavers. No encroachments into the spinal
canal or foramen transversarium occurred. However, two screws were superiorly
directed and violated the occipitocervical joint; they were not parallel to IAC1.
CONCLUSION: MEC1 provides a fixed and reliable landmark for ALM instrumentation.
An entry point 2 mm point lateral to MEC1 is close to ALM midpoint. IAC1 also
provides a guide for the sagittal trajectory. Attention to anatomic landmarks may
help reduce complications associated with atlas instrumentation but should be
verified in future clinical studies.
PMID- 28694592
TI - Trends in the use of patient-reported outcome instruments in neurosurgical adult
thoracolumbar deformity and degenerative disease literature.
AB - OBJECTIVE: Shifting national healthcare trends place increased emphasis on
patient-centered care and value-based outcomes, and thus, patient-reported
outcome instruments (PROIs) are often used. We sought to characterize the trends
in PROI use over the past decade with regard to thoracolumbar degenerative spine
disease and spinal deformity in major neurosurgical journals. METHODS: Articles
were screened for PROI use through a PubMed search among five major neurosurgical
journals from 2006 to 2016. Articles focusing on adult thoracolumbar deformity
and degenerative disease were selected with stringent criteria to further
characterize PROI use. RESULTS: A total of 29 different PROIs were used among 102
articles identified from 2006 to 2016 using our search strategy. Journal of
Neurosurgery: Spine contained the most articles utilizing PROIs with 35.3% of all
articles meeting search criteria. The most frequently used PROIs were Oswestry
Disability Index, visual analog scale, and the European Quality of Life Five
dimension questionnaire used in 79.4%, 59.8%, and 29.4% of articles,
respectively. Linear regression identified a significant increase in the number
of articles employing PROIs from 2006 to 2016 (Y = 1.85, R2= 0.77, P < 0.01). The
total number of PROIs per article was relatively stagnant over time and did not
significantly change (Y = 0.03, R2= 0.05, P = 0.51). CONCLUSIONS: PROI use as an
outcome tool in the adult thoracolumbar disease literature has increased during
the past decade, which may be an indicative of PROI use to define patient
expectations. This may also represent a trend toward PROI use as a surrogate
measure of value-based care.
PMID- 28694593
TI - Experimental study on pressure response to graded spinal canal compromise in an
in vitro burst fracture mode.
AB - BACKGROUND: Spinal cord compression is a known cause of spinal cord injury. The
purpose of this study is to measure pressure response during graded spinal cord
compression. This information will be important in evaluating the amount of canal
compromise that can be tolerated before risking neurological injury secondary to
cord compression. To date, there is no published study that has evaluated
pressure response to graded canal compromise in the thoracic and lumbar spine.
MATERIALS AND METHODS: A comparative biomechanical investigation using an in
vitro burst fracture model of graded spinal canal compromise was performed. Four
porcine spines, sectioned into four thoracics and four lumbar segments, were
harvested from 30 kg pigs. Graded spinal canal compromise (0.75 mm/30 s) was
achieved using a modified 12.7 mm dynamic hip screw. The real-time ventral
epidural pressure was measured at each 0.75 mm of canal compromise. RESULTS: A
significant increase in spinal cord pressure was recorded during graded spinal
cord compression (P < 0.0001), and there were no statistical differences between
the increase in pressure measured in the thoracic and lumbar spinal segments (P =
0.83). The pressure to degree of canal compromise curve exhibited an initial
rapid rise in pressure followed by incrementally smaller increases in pressure as
canal compromise increased. CONCLUSIONS: Spinal cord pressure increased with any
degree of canal compromise, the most important rise occurring with initial
compression. Future studies will evaluate the usefulness of laminectomy in vivo
to completely restore ventral epidural pressure in the thoracic and lumbar spine.
PMID- 28694594
TI - Free hand technique of cervical lateral mass screw fixation.
AB - STUDY DESIGN: We introduce a simple free hand technique with great ease of
application, without angles, measures or degrees, and without any fluoroscopic
guidance. It is a safe and reproducible technique. We present our preliminary
experience with the use this technique, with inimitable simplicity. PURPOSE: The
primary aim of the procedure was to achieve adequate screw trajectory in an
apparent challenging ease which is reproducible with a good outcome. OVERVIEW OF
LITERATURE: Lateral mass screw fixation is used for posterior subaxial cervical
fixation. It was described by Louis and Magerl, then by Anderson, An, and
Ebraheim et al. Each one described the procedure with a unique screw entrance
point and trajectory. TECHNICAL NOTE: This study is a prospective case study of
45 patients who underwent subaxial cervical lateral mass screw fixation. The
screws were inserted using a free hand method. The described free hand technique
was found to minimize the morbidity associated with other techniques without
compromising the quality of fixation. CONCLUSIONS: Surgical experiences with this
technique found it equally safe, rapid, easy, and reproducible.
PMID- 28694595
TI - Minimally invasive "separation surgery" plus adjuvant stereotactic radiotherapy
in the management of spinal epidural metastases.
AB - AIM: This study aimed to describe the application of minimally invasive surgery
(MIS) in separation surgery combined with postoperative stereotactic body
radiation therapy (SBRT) in patients with symptomatic metastatic epidural spinal
disease. METHODS: Three techniques are described: (1) MIS posterior separation
surgery alone, (2) MIS posterolateral separation surgery with percutaneous
pedicle screw placement, and (3) MIS lateral corpectomy with percutaneous pedicle
screw placement. Seven representative cases are presented in which the above
techniques were applied and after which postoperative SBRT was performed.
RESULTS: The seven representative patients (3 male, 4 female) had a mean age of
54 years (range, 46-62 years). Two patients had a primary diagnosis of
cholangiocarcinoma and in one patient each a diagnosis of breast, renal, lung
adenocarcinoma, melanoma, and urothelial squamous cell carcinoma as their primary
tumor. All patients had additional multiorgan disease apart from the metastatic
spine involvement. Three patients underwent operations in the lumbar spine, two
in the thoracic spine, and one in each of the thoraco-lumbar and lumbo-sacral
spine. The average operating time was 149 +/- 60.3 min (range, 90-240 min). The
mean estimated blood loss was 188.8 cc. The mean length of stay in the hospital
was 4 days (range, 3-7 days). There were no surgical complications. All patients
received postoperative SBRT (typically 24 Gy in 3 fractions) at a mean of 43.2
days after surgery (range, 30-83). CONCLUSIONS: Early reports such as this
suggest that MIS techniques can be successfully and safely applied in
accomplishing "separation surgery" with adjuvant SBRT in the management of
metastatic spinal disease. The potential advantages conferred by MIS techniques
such as shortened hospital stay, decreased blood loss, reduced perioperative
complications, and earlier initiation of adjuvant radiation are highly desirable
in the treatment of this challenging patient population.
PMID- 28694596
TI - Cadaveric study for ideal dorsal pedicle screw entry point.
AB - OBJECTIVE: To determine the entry for the dorsal pedicular screw in relation to
the notch present at the junction of base of the lateral margin of superior
articular process with superior border of transverse process in dorsal spine. The
advantage of this technique is a constant and easily identifiable entry point
which does not involve partial resection of the inferior facet, thus maintaining
stability and maintaining the well defined transverse and sagittal screw angles
and decreasing the incidence of medial and inferior pedicle violation. MATERIALS
AND METHODS: The study was carried out using ten cadavers (four male and six
female). Spinal column was dissected completely from cadavers. Before the
experiment, normal anatomy was confirmed on all cadavers excluding cases of
spinal deformity. Dissection was done by the spine surgeons taking care to
preserve all the bony landmarks near the entry point. This study was carried out
bilaterally on pedicles between the first and twelfth thoracic (T) vertebrae.
RESULTS: The relation of the superior articular notch and transverse process to
the thoracic spine pedicles was studied. It was found that superior third of the
pedicle was related to the superior articular notch and the transverse process in
the first five thoracic vertebrae. The relation of these structures to the
pedicle of the sixth thoracic vertebra was somewhat equally distributed between
the superior and middle third of the pedicle. From the 7th to 12th thoracic
vertebrae the superior articular process and transverse process were related to
the middle third of the pedicle in almost all the cases. It is important to note
that the inferior 1/3rd of the pedicle was not related to these landmarks at any
of the levels. CONCLUSION: We conclude that the ideal pedicle entry point
described here should be considered by surgeons during thoracic pedicle screw
instrumentation. The notch at the base of the superior articular process will
always remain constant and therefore an important anatomical landmark in guiding
the screw toward the entry of the pedicle.
PMID- 28694597
TI - Management of cervical monoradiculopathy due to prolapsed intervertebral disc, an
institutional experience.
AB - BACKGROUND: Cervical radiculopathy is the common clinical entity, often caused by
"wear and tear" changes that occur in the spine. In the younger population,
cervical radiculopathy is a result of a disc herniation or an acute injury
causing foraminal impingement of an exiting nerve, whereas in the older
individuals, it is due to foraminal narrowing from osteophyte formation,
decreased disc height, and degenerative changes of the uncovertebral joints
anteriorly and of the facet joints posteriorly. In most (75%-90%), cervical
radiculopathy responds well to conservative treatment, whereas the remaining
patients, who fail to achieve acceptable recovery with conservative modalities,
alone need surgical decompression of the nerve root. Surgical interventions can
be categorized into anterior and posterior approaches to the spine. Our study is
focused on the surgical outcome of anterior discectomy with fusion versus
posterior cervical discectomy with foraminotomy for cervical monoradiculopathy.
MATERIALS AND METHODS: Ours is a retrospective study including patients of one
level unilateral posterolateral cervical disc prolapse with radiculopathy
operated in Department of Neurosurgery, Bangalore Medical College and Research
Institute between 2012 and June 2016. The hospital records, imagings, operation
notes, and follow-up records were reviewed and analyzed. One hundred and fourteen
patients of cervical monoradiculopathy were investigated and operated, 76
operated by anterior cervical discectomy with fusion (ACDF), and 38 operated by
posterior cervical laminoforaminotomy (PCL). RESULTS: The average operation time
in 76 patients of ACDF group was 178 min and in 38 patients of PCL group was 72
min. Sixty-nine (91%) patients of ACDF and 38 (100%) patients of PCL had
symptomatic relief but statistically (P > 0.5) was not significant. Three
patients in ACDF group had hoarseness of voice due to recurrent laryngeal nerve
palsy and there were no fresh permanent neurological deficits in any patients of
PCL group over a follow-up period of 36 months. The average postoperative
hospital stay was 5 days in ACDF group and 3 days in PCL group. The average
intraoperative blood loss was <50 ml in ACDF group and 650 ml in PCL group. The
need of analgesic for pain arising from bone graft site in ACDF group was
comparable with operative site pain in PCL group. CONCLUSIONS: PCL is a simple
approach, yields gratifying results, and is a promising alternative in selected
cases of cervical monoradiculopathy due to disc prolapse.
PMID- 28694598
TI - Successful brace treatment of Scheuermann's kyphosis with different angles.
AB - BACKGROUND: Scheuermann's disease is regarded as the most common cause of
structural hyperkyphosis within adolescents without any proper treatment. It may
lead to progressive deformity and back pain which influences patient's quality of
life during adolescence and adulthood. Treatment approach to Scheuermann's
kyphosis has not been clearly defined due to its different definitions and
obscure natural history. The goal of treatment is not only to prevent progression
but also to obtain permanent correction. Bracing, especially Milwaukee brace and
physiotherapy are two of the common nonoperative treatment modalities. Hence, the
present study intended to evaluate the effectiveness of Milwaukee brace on
progression control as well as correction of Scheuermann's kyphosis. MATERIALS
AND METHODS: In a retrospective, observational study, all the patients diagnosed
with Scheuermann's kyphosis were reviewed in 2003-2013, who were treated by
Milwaukee brace at a single center. There was a minimum of 2-year follow-up after
completion of bracing, during which clinical and radiological parameters were
identified and recorded. RESULTS: The mean angle of kyphosis in these patients at
the presentation was 63.24 +/- 9.96 and at the end of this study was 36.5 degrees
+/- 13.4 degrees (P < 0.001). Moreover, mean improved angle in those patients
with <75 degrees of kyphosis was 25.26 degrees +/- 7.78 degrees and in those
with 75 degrees or more than 75 degrees of kyphosis was 26.77 degrees +/-
19.76 degrees (P < 0.001). CONCLUSION: Conservative treatment with Milwaukee
brace and physiotherapy was effective in our hand for halting kyphosis
progression in 97.5% of Scheuermann's kyphosis, which could be advised for cases
up to 90 degrees of kyphosis before skeletal maturity. As a result, a trial of
brace treatment could be recommended in patients with severe kyphosis (up to 90
degrees ) which can open a new insight in conservative treatment of Scheuermann's
kyphosis.
PMID- 28694599
TI - Segmental spinal dysgenesis associated with occult dysraphism: Considerations on
management strategies.
AB - Segmental spinal dysgenesis is a rare and challenging entity especially when
associated with occult dysraphism. Experience with a female patient followed
during a period of 10 years spanning from 5 to 15 years of age is reported.
During that period the girl underwent three spinal operations consisting in one
decompression and spinal cord untethering, one posterior instrumented fusion and
a spinal cord re-untethering. Clinical and radiological features are discussed
and considerations on optimization of management strategies are made.
PMID- 28694600
TI - Long-term resolution of delayed onset hypoglossal nerve palsy following occipital
condyle fracture: Case report and review of the literature.
AB - The authors present the case of a patient that demonstrates resolution of delayed
onset hypoglossal nerve palsy (HNP) subsequent to occipital condyle fracture
following a motor vehicle accident. Decompression of the hypoglossal nerve and
craniocervical fixation led to satisfactory long-term (>5 years) outcome. There
is a scarcity of literature in recognizing HNPs following trauma and a lack of
pathophysiological understanding to both a delayed presentation and to resolution
versus persistence. This is the first report demonstrating long-term resolution
of hypoglossal nerve injury following trauma to the craniocervical junction.
PMID- 28694601
TI - Spastic quadriparesis due to pathological fracture of odontoid secondary to
carcinoma prostate: A rare presentation.
AB - Prostate carcinoma presenting as symptomatic metastases to atlantoaxial spine is
extremely rare. Spastic quadriparesis due to pathological fracture of odontoid as
the only initial manifestation without symptoms of primary malignancy is rarer
still. We report a 64-year-old male who presented with progressive spastic
quadriparesis along with urinary retention of 3 weeks duration. Computed
tomography and magnetic resonance imaging cervical spine and craniovertebral
junction showed type III pathological fracture of odontoid with anterior
translation of C1 with spinal cord compression. Biopsy from an enlarged prostate
showed adenocarcinoma of prostate. The patient was managed conservatively from
neurological aspect as he refused for any surgical intervention.
PMID- 28694602
TI - Pseudarthrosis due to galvanic corrosion presenting as subarachnoid hemorrhage.
AB - Two unlike metals near one another can break down as they move toward
electrochemical equilibrium resulting in galvanic corrosion. We describe a case
of electrochemical corrosion resulting in pseudarthrosis, followed by
instrumentation failure leading to subarachnoid hemorrhage. A 53-year-old female
with a history of cervical instability and two separate prior cervical fusion
surgery with sublaminar cables presented with new onset severe neck pain.
Restricted range of motion in her neck and bilateral Hoffman's was noted. X-ray
of her cervical spine was negative. A noncontrast CT scan of her head and neck
showed subarachnoid hemorrhage in the prepontine and cervicomedullary cisterns.
Neurosurgical intervention involved removal of prior stainless steel and titanium
cables, repair of cerebrospinal fluid leak, and nonsegmental C1-C3 instrumented
fusion. She tolerated the surgery well and followed up without complication.
Galvanic corrosion of the Brook's fusion secondary to current flow between
dissimilar metal alloys resulted in catastrophic instrumentation failure and
subarachnoid hemorrhage.
PMID- 28694603
TI - Hydatid disease of the spine: A rare case.
AB - Hydatid disease or hydatidosis is the most widespread zoonosis caused by
Echinococcus granulosus. Liver and lungs are the most common sites. Bone
involvement is rare and reported in 0.5%-4% with spinal involvement reported in
50% of these cases. We present a case of spinal hydatidosis in a 35-year-old male
presenting with lower extremity weakness and numbness. Magnetic resonance imaging
(MRI) of the spine showed multiple cystic lesions at the T9-T11 level with
involvement of the paraspinal muscles. The lesion was seen intraspinal,
intradural, intramedullary, and epidural. Radiological impression was aneurysmal
bone cyst. The patient underwent laminectomy, and the excised cysts showed
characteristic features of hydatid cyst (HC) on histopathology. The patient was
started on antihelminthic therapy postoperatively. MRI is a diagnostic modality
for HC, but the unusual location and absence of characteristic features can cause
diagnostic difficulty. A high index of suspicion should be kept in patients
residing in endemic areas and presenting with unusual cystic lesion of spine.
PMID- 28694604
TI - Posterior fixation as the sole treatment for ossified posterior longitudinal
ligament?
PMID- 28694605
TI - Respiratory Involvement in Guillain-Barre Syndrome: The Uncharted Road to
Recovery.
PMID- 28694606
TI - Epidermoid Cysts of the Quadrigeminal Cistern: Neuropsychiatric Symptoms and
Management.
PMID- 28694607
TI - Hypoparathyroidism Should Always Be Checked in Papilledema.
PMID- 28694608
TI - Surgically Relevant Bony Anatomical Variations in Paraclinoid Aneurysms-Three
Dimensional Multi-Detector Row Computed Tomography-Based Study.
AB - OBJECTIVE: To evaluate the proportion of surgically relevant anatomical
variations such as caroticoclinoid foramen, interclinoid osseous bridge, and
anterior clinoid pneumatization in patients with paraclinoid aneurysms based on
computed tomography (CT) cerebral angiography studies. MATERIALS AND METHODS:
Fifty-four CT cerebral angiography studies showing paraclinoid aneurysms
involving the cavernous, clinoid, and supraclinoid internal carotid artery (ICA)
were retrospectively evaluated. Source images were processed for three
dimensional reconstructions to evaluate the presence and type of caroticoclinoid
foramen, interclinoid osseous bridge, and multiplanar reconstructions with bone
algorithm to study the type of pneumatization. RESULTS: The study included 30
female and 24 male patients with mean age of 45.61 (10.47) years. Among the 108
sides studied in 54 patients, caroticoclinoid foramen was seen in 24 cases
(22.22%), interclinoid osseous bridge was seen unilaterally in 1 case (0.9%), and
pneumatization of anterior clinoid process occurred in 12 cases (11.11%).
Incomplete caroticoclinoid foramen (11 cases) and Type I pneumatization (7 cases)
were seen to be predominant subtypes. There was no statistically significant
gender difference in the occurrence of caroticoclinoid foramen and anterior
clinoid pneumatization. Seventy-four aneurysms were detected in 54 patients.
Based on their location, 46 aneurysms involved supraclinoid ICA, 18 aneurysms in
the clinoid segment, and 10 aneurysms in the cavernous segment. Caroticoclinoid
foramen was most prevalent in clinoid aneurysms with 12 cases occurring in the
clinoid segment. CONCLUSION: Notable proportions of caroticoclinoid foramen and
pneumatization occur in cases of paraclinoid aneurysm. Radiological reports
should emphasize on these surgically relevant bony anatomical variations.
PMID- 28694609
TI - Role of Biofilm in Cerebrospinal Fluid Shunt Infections: A Study at Tertiary
Neurocare Center from South India.
AB - INTRODUCTION: Biofilms are the source of persistent infections of many pathogenic
microbes. They are responsible for nosocomial infection and also associated with
many surgical conditions including indwelling medical devices such as
ventriculoperitoneal shunt. A significant problem encountered in shunt procedures
is obstruction followed by infection, with infection rate ranging from 2% to 27%,
often with poor outcome. MATERIALS AND METHODS: This study was conducted in the
Department of Neuromicrobiology at a tertiary neuroinstitute for 6 months from
July 1 to December 31, 2014. The samples comprised cerebrospinal fluid (CSF) from
suspected cases of shunt infections. Laboratory diagnosis of causative agent was
established by adopting standard procedures. Then, isolates were evaluated for
production of biofilm by tissue culture plate (TCP) method and tube method.
RESULTS: Of the 1642 shunt CSF samples obtained from neurosurgery, 14.79% were
culture positive which yielded 254 isolates. About 51.97% were Gram-negative
bacilli (GNB), 46.46% were Gram-positive cocci (GPC), and 1.57% were Candida
albicans. Among GNB, nonfermenters were the most common (51.52%) followed by
Pseudomonas aeruginosa (15.9%). Among GPC, coagulase-negative Staphylococci were
88.13%, out of which 43.26% were methicillin-resistant. Other GPC were
Enterococcus spp. (4.24%), Staphylococcus aureus (5.08%), and Streptococcus spp.
(2.54%). Among all isolates, 120 were tested for biofilm production, out of which
57.5% were biofilm producers and 42.5% were nonproducers. CONCLUSIONS: TCP was
the better method to detect biofilm. Most of the biofilm producers were resistant
pathogens.
PMID- 28694610
TI - Comparison of Efficacy of Intraoperative Indocyanine Green Videoangiography in
Clipping of Anterior Circulation Aneurysms with Postoperative Digital Subtraction
Angiography.
AB - INTRODUCTION: The aim of this study is to assess the efficacy of intraoperative
indocyanine green videoangiography (ICG-VA) using postoperative digital
subtraction angiography (DSA) in clipped anterior circulation aneurysms.
MATERIALS AND METHODS: A prospective study was conducted for 1 year which
included thirty patients of anterior circulation aneurysm treated by clipping of
aneurysm. Intraoperative ICG-VA was performed on all the patients. Postoperative
DSA was performed to assess the efficacy of ICG-VA. RESULTS: Intraoperative ICG
VA revealed the occlusion of aneurysm in all the thirty patients. Postoperative
DSA revealed aneurysm neck remnant in two patients and demonstrated no branch
occlusion. CONCLUSIONS: Intraoperative ICG-VA is useful in assessing the
completeness of clipping of cerebral aneurysms and ensures patency of branch
vessels, thus providing a better postoperative outcome. It replaces the need for
invasive postoperative angiographic imaging in a selected group of patients and
is also cost effective.
PMID- 28694611
TI - Depression as a Manifestation of Obstructive Sleep Apnea.
AB - BACKGROUND: Obstructive sleep apnea (OSA) often results in a wide range of
comorbid conditions, predominantly of the cardiovascular/respiratory,
endocrine/metabolic, and neuropsychiatric symptoms. In view of the ambiguity of
literature regarding the association between OSA and depression, we conducted
this study to show any association between the two disorders. OBJECTIVE: The aim
of the study was to see the association between OSA and depression and to study
the prevalence of OSA in patients suffering from depression. METHODS: We
performed polysomnography (PSG) studies of patients that were referred from
various subspecialty clinics from July 2011 to August 2013. Psychiatric diagnosis
was done using mini international neuropsychiatric interview plus scale. This was
followed by application of Hamilton Depression Rating Scale (HAM-D). Standard
methods of statistical analysis were used for data analysis. RESULTS: Out of 182
patients who underwent PSG, 47 were suffering from depression with a mean age
significantly more (P < 0.001) than that of other population (58.60 years vs.
53.60 years). In our 47 depressed patients, 44 (93.6%) had abnormal PSG. Based on
apnea-hypopnea index score, 3 (6.8%) patients had mild, 18 (40.9%) had moderate,
and 23 (52.3%) had severe OSA. The mean HAM-D score was significantly more in
depression patients, (17. 35 +/- 5.45) as compared to non depressive patents
(8.64 +/- 6.24) (P = 0.0001). CONCLUSION: This study demonstrates significant
overlap between the sleep apnea and depression. Health specialists need more
information about screening for patients with OSA to ensure proper diagnosis and
treatment of those with the condition. Most of the clinicians do not suspect this
important comorbidity of depression in the beginning resulting in delayed
diagnosis.
PMID- 28694612
TI - Cerebral and Coronary Vasculature in Disease Associations and Dissociations in
the South Indian Population.
AB - INTRODUCTION: Cerebrovascular accidents constitute the most common cause of
disability all over the world. In India prevalence rate is 545 per 100000 and
mortality rate is around 7.5 per thousand. Therefore the authors undertook a
study on patients who underwent coronary artery bypass surgery (CABG). They were
investigated for clinical and/or radiological evidence of cerebrovascular disease
(CVD) with the aim to decide on early neurological intervention. PATIENTS AND
METHODS: 210 patients who had undergone CABG were evaluated with neck vessel
Doppler using high resolution duplex scanner system and computed tomography (CT)
scan as well as MR angiogram (MRA) in addition to assessment of co morbid risk
factors. RESULTS: 91% of patients who had undergone CABG had radiological
evidence of CVD. The most common risk associated with CAD and CVD was
Hypertension (HT), DM, dyslipidemia and combined HT and DM in that order. Neck
vessels were normal in 59%. Significant disease was found in only 7.2%. Internal
carotids were abnormal in 82%. Infarcts were seen in 82.1%. DISCUSSION: This
study reveals patients with CAD have a high degree of asymptomatic CVD. It is
mostly due to small vessel disease including internal carotids but not so much
with large vessels. Therefore, patients with CAD carry a high risk of vascular
cognitive dysfunction. This can be reduced by effective management of the
systemic risk factors. Screening for large vessel disease which is commonly done
is likely to give a false sense of security. CONCLUSION: As against western
population Indians seem to have small and medium sized vessels disease in the
setting of CAD.
PMID- 28694613
TI - Cognitive and Functional Outcomes following Inpatient Rehabilitation in Patients
with Acquired Brain Injury: A Prospective Follow-up Study.
AB - OBJECTIVES: To study the effects of cognitive retraining and inpatient
rehabilitation to study the effects of cognitive retraining and inpatient
rehabilitation in patients with acquired brain injury (ABI). DESIGN AND SETTING:
This was a prospective follow-up study in a neurological rehabilitation
department of quaternary research hospital. PATIENTS AND METHODS: Thirty patients
with ABI, mean age 36.43 years (standard deviation [SD] 12.6, range 18-60), mean
duration of illness 77.87 days (SD 91.78, range 21-300 days) with cognitive,
physical, and motor-sensory deficits underwent inpatient rehabilitation for
minimum of 14 sessions over a period of 3 weeks. Nineteen patients (63%) reported
in the follow-up of minimum 3 months after discharge. Type of ABI, cognitive
status (using Montreal Cognitive assessment scale [MoCA] and cognitive Functional
Independence Measure [Cog FIM](r)), and functional status (motor FIM(r)) were
noted at admission, discharge, and follow-up and scores were compared. RESULTS:
Patients received inpatient rehabilitation addressing cognitive and functional
impairments. Baseline MoCA, motor FIM, and Cog FIM scores were 15.27 (SD = 7.2,
range 3-30), 31.57 (SD = 15.6, range 12-63), and 23.47 (SD = 9.7, range 5-35),
respectively. All the parameters improved significantly at the time of discharge
(MoCA = 19.6 +/- 7.4 range 3-30, motor FIM(r) = 61.33 +/- 18.7 range 12-89, Cog
FIM(r) =27.23 +/- 8.10 range 9-35). Patients were discharged with home-based
programs. Nineteen patients reported in follow-up and observed to have maintained
cognition on MoCA (18.8 +/- 6.8 range 6-27), significantly improved (P < 0.01) on
Cog FIM(r) (28.0 +/- 7.7 range 14-35) and motor FIM(r) =72.89 +/- 16.2 range 40
96) as compare to discharge scores. CONCLUSIONS: Cognitive and functional
outcomes improve significantly with dedicated and specialized inpatient
rehabilitation in ABI patients, which is sustainable over a period.
PMID- 28694614
TI - Environmental Arsenic Contamination and Its Effect on Intelligence Quotient of
School Children in a Historic Gold Mining Area Hutti, North Karnataka, India: A
Pilot Study.
AB - CONTEXT: Arsenic is a rare crystal element that naturally occurs in all
environmental media. A combination of regional and site-specific biogeochemical
and hydrological factors governs its dispersion in the environment. It has far
reaching consequences on human health. Exposure to arsenic in drinking water has
been associated with a decline in intellectual function in children. AIM: The aim
of this study is to assess the relationship between exposure to arsenic by
drinking water and children's intelligence in Karnataka state, India. SETTINGS
AND DESIGN: Twenty school children of age 10-14 years from Sandur, Bellary,
Karnataka, and from Hutti, Raichur, Karnataka, were categorized as control and
study group, respectively. SUBJECTS AND METHODS: Water samples were collected
from both the villages for the analysis of arsenic and fluoride levels. Hair and
nail samples were collected from the participants, and the arsenic levels were
determined. Intelligence quotient (IQ) assessment was done using the Raven's
Standard Progressive Matrices. STATISTICAL ANALYSIS USED: Chi-square test, Mann
Whitney U-test, and Fisher's exact test. P < 0.05 was considered statistically
significant. RESULTS: There was a significant increase in the arsenic content in
the hair and nail samples of children in the study group. The mean IQ tests score
in the control group and study group was 30.55 and 17.95, respectively, and this
difference was statistically significant. CONCLUSION: Chronic arsenic exposure
could be a possible cause for the reduced IQ scores seen in children residing in
Hutti, Raichur District, North Karnataka.
PMID- 28694615
TI - Prevalence of Autism Spectrum Disorder among Rural, Urban, and Tribal Children (1
10 Years of Age).
AB - INTRODUCTION: Studies on autism spectrum disorders (ASDs) have largely focused on
children in specific settings. The current scenario of research in ASDs is
limited largely to clinic-based case reports, case series, and retrospective
chart reviews. The present study is the first population-based prevalence study
conducted across rural, urban, and tribal populations in India. MATERIALS AND
METHODS: A cross-sectional two-phase study was conducted covering children in the
age group of 1-10 years of age across geographical regions representing rural,
urban, and tribal populations. The first phase (screening phase) involved
administration of the Hindi version of the Indian Scale for Assessment of Autism.
Those identified as suspected of ASD and 10% of all classified as nonsuspects for
autism were also evaluated by the clinical team in second phase (evaluation
phase). RESULTS: Forty-three children out of a total of 28,070 children in rural,
urban, and tribal area in the age group of 1-10 years were diagnosed as cases of
ASD yielding a prevalence of 0.15% (95% confidence interval [CI] =0.15-0.25).
Logistic regression analysis showed a two times significantly higher risk of
diagnosing ASD in rural area as compared to tribal (odds ratio [OR]; 95% CI =
2.17 [1.04-4.52], P = 0.04). Male sex and upper socioeconomic group of head of
family/father had a higher risk of getting diagnosed as autism as compared to
lower socioeconomic group (OR; 95% CI - 3.23; 0.24-44.28, P = 0.38). CONCLUSIONS:
Estimation of true prevalence of ASD in India is going to improve policies on
developmental disabilities.
PMID- 28694616
TI - Reoperation in Spinal Dysraphism: Does it Help in Reversing the Neurological
Deficits?
AB - AIMS: After initial primary repair by inexperienced hands for the spectrum of
pathological conditions in spinal dysraphism (SD), a few percentage of patients
present with recurrent symptoms and worsening neurological status especially when
primarily pathology is not identified and dealt properly. When the primary
intradural tethering element is left untouched, worsening of symptoms is common.
In this retrospective study, we tried to analyze the symptomatology, functional
outcome at 1-2 months after the second surgery and associated complications.
SUBJECTS AND METHODS: All patients underwent second surgery at author's
institution. Pre and post-operative data were evaluated using Necker -Enfants
Malades (NEM) neurological and modified Hoffer ambulatory scale. RESULTS: The
main presenting complaints were bladder incontinence and limb weakness.
Preoperative mean scores for motor and bladder were 3.56 and 2.78 out of 5, 2.67
out of 4, and 2.11 out of 3 for bowel and sensory function, respectively.
Postoperative mean score for motor, sensory, bladder, and bowel function revealed
good neurological improvement. Statistically neurological improvement in bladder
and bowel function was significant. More than 60% of patients had normal
ambulation at follow-up. CONCLUSIONS: Patients presenting with recurrent symptoms
in an operated case of SD need to be investigated, cause of recurrence has to be
identified, and if needed repeat surgery is recommended at the earliest. Long
standing neurological deficits can potentially improve, especially bladder and
bowel function which gives a good quality of life to the patients. Furthermore,
we want to stress the fact that since it is an intradural pathology, these cases
should be operated by experienced neurosurgeons, and this fact should be made
aware among referring doctors.
PMID- 28694617
TI - Is Depression Related to Low Folate Levels in People with Epilepsy? An
Observational Study and Meta-analysis.
AB - BACKGROUND: Both depression and low serum levels of folate are common in people
with epilepsy (PWE), the latter especially in patients on hepatic enzyme-inducing
antiepileptic drugs (AEDs). We did a cross-sectional study and a meta-analysis to
assess if lower folate levels have any relation with depression in PWE. MATERIALS
AND METHODS: Two hundred and one PWE were recruited and assessed for depression
using the Inventory of Depressive Symptomatology-Self-Rated (IDS-SR) and
Inventory of Depressive Symptomatology-Clinician Rated; serum folate levels were
measured in them at the same time. Literature search was carried out and studies
with data on depression as well as folate levels in PWE were included.
Statistical analysis to determine frequency of depression, low folate levels, and
relation between them among our cases and the pooled data from the included
studies was done. RESULTS: Depression was observed in 65.68% and low serum folate
(<4 ng/ml) in 48.75% of PWE (over 80% on older AEDs); there was no statistically
significant correlation between them. However, on analyzing the pooled data of
six studies including the present, the Fisher's z-transformed correlation
coefficient was -0.1690 (95% confidence interval [-0.3175, -0.0124], P = 0.0464).
CONCLUSIONS: Depression and low folate levels are common in PWE. Low folate
levels have a mild but significant negative correlation with depression in this
population, and folate supplementation would be advisable for those on the older
AEDs.
PMID- 28694618
TI - Single Parietal Burr-hole Craniostomy with Irrigation and Drainage for Unilateral
Chronic Subdural Hematoma in Young Adults <40 Years: A Rationale behind the
Procedure.
AB - BACKGROUND: Chronic subdural hematoma (CSDH) is one of the most common
neurosurgical conditions. It is mostly a disease of elderly population with very
little data about the young patients. There is also the debate regarding
treatment strategies. We decided to determine the overall efficacy of the single
burr-hole craniostomy (SBHC) for unilateral CSDH in young adults <40 years.
SUBJECTS AND METHODS: We performed a retrospective study of young patients
undergoing SBHC for unilateral CSDH between January 2013 and June 2016 at our
institution. Medical records were assessed based on patient characteristics in
the form of sex of the patient, etiology, presenting symptoms, comorbidities, and
signs including Glasgow Coma Scale, computed tomography (CT) brain findings (site
and thickness of SDH with midline shift), and intraoperative presence of
chronic/subacute component. RESULTS: Mean age of the patient was 33.69 years
(range 18-40 years), mean thickness of SDH was 15.47 mm, and mean midline shift
was 11.26 mm. 61.54% patients were male, trauma being the most common etiology
(92.31%) with most common presenting complaint being headache (90.38% patients).
69.23% patients presented within 1 day of onset of symptoms. On CT scan, most of
the patients were having SDH thickness between 11 and 20 mm (67.31%) with midline
shift of 6-10 mm (53.85%). Right-sided SDH was present in 53.85%.
Intraoperatively, 63.46% patients had subacute SDH whereas 34.61% had chronic
component. There were total 2 recurrences (3.85%). CONCLUSIONS: Young adults who
present with unilateral CSDH usually have a history of trauma. They have shorter
duration of symptoms and present mainly with the features of raised intracranial
pressure such as headache and vomiting. SBHC with irrigation and drainage has
excellent result for unilateral CSDH in young adults compared to other methods of
drainage and should be considered treatment of choice unless contraindicated.
PMID- 28694619
TI - Mental Health Orientation for Self-Help Group Members: A Feasibility Study.
AB - BACKGROUND: Treatment gap for mental health care in low- and middle-income (LAMI)
countries is very large, and building workforce using the locally available
resources is very much essential in reducing this gap. The current study is a
preliminary work toward this direction. MATERIALS AND METHODS: A single group pre
and post-design was considered for assessing the feasibility of Mental Health
Orientation (MHO) Program for Self-Help Group members. Assessment of
participants' MHO using Orientation Towards Mental Illness (OMI) scale was
undertaken at three levels: Baseline assessment before the intervention, after
completing 2 days orientation program, and 6 weeks later. RESULTS: Analysis of
data resulted in statistically significant mean scores in the domains of areas of
causation (F[1.41, 40.7] = 21.7, P < 0.000, etap2 = 0.428), perception of
abnormality (F[1.27, 36.8] = 15.8, P < 0.000, etap2 = 0.353), treatment (F[1.42,
41.3] = 34.8, P < 0.000, etap2 = 0.546), and after effect (F[1.36,39.4] = 26.7, P
< 0.000, etap2 = 0.480). Although the overall mean scores of all the domains of
OMI were found to be statistically significantly different, there was no
significant difference in the mean scores between post and follow-up assessments
on areas of causation (MUd = 1.27, P = 0.440) and treatment (MUd = 1.00, P =
0.156). CONCLUSION: Overall, the findings of our study demonstrate that brief MHO
program can exert a beneficial effect on bringing about significant change in the
orientation of the participants toward mental illness but need to be refreshed
over time to make the impact of the program stay longer.
PMID- 28694620
TI - Nonalcoholic Wernicke's Encephalopathy: A Retrospective Study from a Tertiary
Care Center in Northern India.
AB - OBJECTIVE: The objective of this study was to describe the demographic features,
clinical presentation, and management and outcome of fifty cases of nonalcoholic
Wernicke's encephalopathy from a tertiary care hospital of a region with reported
incidence of thiamine deficiency disorders. MATERIALS AND METHODS: In a
retrospective study, fifty adult cases of Wernicke's encephalopathy were
analyzed. The diagnosis of Wernicke's encephalopathy was made according to the
European federation of neurological societies guidelines 2010. Response to
thiamine replacement and associated brain magnetic resonance imaging (MRI)
findings were also considered as supportive evidence. RESULTS: The mean age of
patients was 50.38 years with 20 males and 30 females. The most common clinical
manifestations were alteration in sensorium in 30 (60%), ataxia in 18 (36%),
memory impairment in 15 (30%), nystagmus in 35 (70%), ophthalmoparesis in 11
(22%), and seizures in 4 (8%). A total of 42 patients had a history of recurrent
vomiting. All patients had polished rice as their staple diet. Thirty-five
patients had associated polyneuropathy and 15 had a gastrointestinal disorder.
Twenty patients underwent MRI which showed both typical and atypical lesions.
Majority of patients showed partial or complete response to intravenous thiamine.
On discharge, the most common residual symptoms were lower limb weakness, ataxia,
and memory impairment. CONCLUSION: The study shows high incidence of nonalcoholic
Wernicke's encephalopathy in the region with predominant causative factor being a
thiamine deficient diet. Recurrent vomiting can be a prominent early symptom of
thiamine deficiency and its recognition can help in the early diagnosis of
Wernicke's encephalopathy and related thiamine deficiency disorders. Thiamine
fortification of food should be done in areas with reported incidence of thiamine
deficiency disorders.
PMID- 28694621
TI - The Challenges of Management of High-grade Gliomas in Nigeria.
AB - BACKGROUND: High-grade gliomas (HGG) are among the most challenging brain tumors
despite many research efforts worldwide. AIM: The aim of this study was to
evaluate the local challenges that may influence outcome of HGG managed in a
neurosurgical center in Nigeria. METHODOLOGY: Retrospective analysis of
prospectively recorded data of patients managed for intracranial HGG at Memfys
Hospital for Neurosurgery, Enugu, Nigeria, between the year 2006 and 2015. Only
cases with conclusive histology following surgery were analyzed. RESULTS: Glioma
was 60 (23.8%) of 252 histology confirmed brain tumors. HGG represented 53.8% of
gliomas with male:female ratio of 2.2:1.0 and peaked from fifth decade of life.
Glioblastoma multiforme accounted for 69% of HGG. At 1-year postsurgery, 53% of
HGGs were dead and 88% of these deaths were in the World Health Organization
Grade IV group. Only 40% of cases could receive adjuvant treatment with only 15%
mortality at 1 year in this subgroup that received adjuvant therapy. In addition,
19% of cases had surgery at Karnofsky score (Ks) of >=70%. However, 94% of
mortality at 1 year was related to surgery at Ks of <=60%. Only four patients had
a tumor volume of <=50 cm3, and among these cases, three patients were
independent at 1 year. Patients with tumor volume above 50 cm3 accounted for 94%
of mortality. CONCLUSION: The peak age incidence for HGG seems to be lower than
in Caucasians. Most cases present late with poor Ks and big tumor volume. The
proportion with access to adjuvant treatment is still poor. Preoperative
Karnofsky, extent of resection, duration of hospital, and Intensive Care Unit
stay have impact on outcome.
PMID- 28694622
TI - Pulmonary Involvement in Patients with Guillain-Barre Syndrome in Subacute Phase.
AB - OBJECTIVES: To evaluate the pulmonary function in Guillain-Barre syndrome (GBS)
patients in subacute phase and find clinical correlates of pulmonary dysfunction.
METHODS: This was a single-center, prospective, cross-sectional, hospital-based
study in GBS patients performed in Department of Neurological Rehabilitation at a
tertiary care institute. Clinical examination for pulmonary function was done by
measuring chest expansion. The pulmonary function tests were carried out by
Spirometry kit Microquark Cosmed, Italy. Fatigue was assessed by Fatigue Severity
Scale, disability status by Hughes Disability Scale (HDS), and muscle weakness by
Medical Research Council sum scores. STATISTICAL ANALYSIS: Statistical analysis
was performed by Stata 11. The significance of P value was adjudged against an
alpha of 0.05. RESULTS: Twenty-eight patients were included with 17 (61%) men and
mean age of 31 years. Median duration of symptoms was 16.5 days. There were 10
(36%) demyelinating and 18 (64%) axonal variants. Twenty-six (93%) patients
scored more than 2 on HDS. All study participants reported fatigue. Twenty-two
(78.6%) patients had chest expansion of <2.5 cm. Spirometry showed restrictive
pulmonary dysfunction in 23 (79%) patients. Significant correlation was found
between abnormal pulmonary function test and chest expansion (P = 0.003).
CONCLUSION: Pulmonary dysfunction in GBS is common even during subacute phase. It
needs to be identified and managed appropriately for better clinical outcome.
PMID- 28694623
TI - Adherence to Antiepileptic Therapy in Adults.
AB - CONTEXT: Epilepsy is a neurological disorder affecting 70 million worldwide. The
high incidence of relapse can be attributed to nonadherence, thus increasing the
incidence of refractory epilepsy to 10%-20%. AIMS: This study was planned to
determine rate of adherence and factors affecting adherence using Antiepileptic
Adherence Questionnaire and Baseline Adherence Questionnaire. MATERIALS AND
METHODS: A cross-sectional, questionnaire-based study was carried out at a rural
hospital from May to September 2015. Patients of either gender aged 18-60 years,
diagnosed with epilepsy were interviewed after they consented. Patient details,
responses to questionnaires were collected and analyzed using descriptive
statistics. RESULTS: Among the participants, 67.8% were males and 32.2% were
females with the mean age of 38.3 +/- 13.9 years. The response rate was 75%
(90/120). The majority were literate (64.4%) and employed (58.9%). The duration
of disease was <5 years in most individuals; 50% were highly, 21.1% moderately,
and 28.9% nonadherent to treatment. Among the highly adherent, 66.7% never
skipped medications because they had knowledge of the disease and treatment. More
than 97% were satisfied with the social support, and 89% expressed that their
family and friends reminded them to take medications. Patients who were
nonadherent to treatment attributed it to the lack of knowledge of the disease
(57%) and treatment (96%). Reasons for nonadherence were patients assumed drug
was harmful, felt cured of the disease, and wanted to avoid side effects.
CONCLUSION: Nearly, 70% expressed the lack of satisfactory support from the
social circle. We observed that nearly seventy percent epileptic patients were
moderate-highly adherent. Nonadherence was attributed to patient feeling cured of
disease and assuming medications to be harmful. Counseling of patients will help
in adherence to treatment.
PMID- 28694624
TI - Neuropsychiatric Manifestations of Scrub Typhus.
AB - Scrub typhus is caused by Orientia tsutsugamushi characterized by focal or
disseminated vasculitis and perivasculitis which may involve the lungs, heart,
liver, spleen and central nervous system. It was thought to have been eradicated
from India. Recently it is being reported from many areas of India. The clinical
picture and severity of the symptoms varies widely. The neurological
manifestations of scrub typhus are not uncommon but are diverse.
Meningoencephalitis is classical manifestation of scrub typhus but cerebellitis,
cranial nerve palsies, plexopathy, transverse myelitis, neuroleptic malignant
syndrome and Guillan-Barre syndrome are other manifestations reported in
literature. The availability of literature on the neurological manifestations of
scrub typhus is limited to case reports mainly. This article reviews various
neurological manifestations of scrub typhus reported in literature.
PMID- 28694625
TI - Does Gender Influence Electroconvulsive Therapy Sessions Required across
Psychiatric Diagnoses? A 5-Year Experience from a Single Center.
AB - CONTEXT: There is a paucity of systematic data reflecting the practice of
electroconvulsive therapy (ECT) from developing countries. AIM: We aimed to
identify the number of ECT sessions required to yield response and gender
diffeferences in the number of sessions across various diagnostic categories.
SETTING AND DESIGN: A record-based study from a teaching cum tertiary care
hospital in South India. SUBJECTS AND METHODS: Case records of patients who
received modified ECT from January 2011 to January 2016 were reviewed. The
sociodemographic details and ECT-related data were collected. Psychiatric
diagnoses were ascertained as per the International Classification of Diseases,
10th Revision criteria. STATISTICAL ANALYSIS USED: Kruskal-Wallis test and Mann
Whitney U-test. RESULTS: Among 148 patients, 82 (55.4%) had mood disorder
(bipolar disorder and recurrent depressive disorder), 43 (29.1%) had
schizophrenia, and 22 (14.9%) had other acute and transient psychotic disorders
(ATPDs). Patients with mood disorders, schizophrenia, and other ATPD received 7.3
(+/- 3.8), 9.7 (+/- 6.1), and 5.4 (+/- 2.0) ECT sessions, respectively, to
achieve response. There was no gender difference in the number of sessions
received. CONCLUSION: Our findings show that number of ECT sessions required to
yield response may be disorder-specific. Gender does not influence the ECT dose
requirement. Variations in ECT parameters across settings may limit the
generalizability of results.
PMID- 28694626
TI - Whether Superficial Abdominal Reflex is Affected by Subcostal Transverse
Abdominal Incisions? A Prospective, Observational Early Experience.
AB - INTRODUCTION: Superficial abdominal reflex (SAR) is an important part of the
neurologic assessment. It is normally present and may be present or absent in
various physiological as well as pathological conditions. The presence of an
abdominal incision creates a dilemma in the mind of the clinician for it
affecting this reflex. As there is no literature on this, we decided to study the
effect of abdominal incisions on SAR. MATERIALS AND METHODS: It was a
prospective, observational study. We evaluated the patients requiring transverse
subcostal incision (range 3-12 cm) both preoperatively and postoperatively, for
their abdominal reflexes. Patients with preoperative normal and symmetrical
abdominal reflexes were included in the study. Postoperatively, we compared the
change of SAR with the preoperative status and analyzed the data. RESULTS: A
total of 94 patients underwent surgeries, out of which 54 patients came under
inclusion criteria, comprising 36 males and 18 females. Subcostal transverse
abdominal incisions were made for surgeries including both gastrointestinal and
ventriculoperitoneal shunts. SAR was found unaffected by the incisions in all
patients. CONCLUSIONS: Although the study was small, subcostal transverse
abdominal incisions were not found to affect SAR.
PMID- 28694627
TI - Osteolytic Skull Lesions-Our Experience.
AB - OBJECTIVE: To present an overview of varied clinical presentations,
investigations and treatment options for Osteolytic skull lesions. STUDY DESIGN:
It is a prospective study. MATERIALS AND METHODS: We conducted this study from
January 2013 to December 2015 in the Department of Neurosurgery, Nil Ratan Sircar
Medical College and Hospital, Kolkata. During this period, 14 patients presented
with osteolytic skull lesions through the outpatient department. All patients
were thoroughly investigated with appropriate hematological and radiological
investigations and treated following admission, and surgery was performed in the
Neurosurgery Department. All were followed regularly in OPD. RESULTS: Total 14
patients were included in the study. Amongst these 7 were male and 7 female. Age
group of patients ranged from 5 to 72 years. Of 14 cases, three cases had dermoid
cyst, four cases had metastasis, and one each case had epidermoid cyst,
intradiploic meningioma, benign cystic lesion, tuberculosis, histiocytosis X,
hemangioma, and osteomyelitis. All underwent diagnostic/therapeutic procedures
and referred for Radio or chemotherapy where indicated. CONCLUSION: All
scalp/skull lesions need careful clinical correlation, appropriate radiological
investigations to establish diagnosis and subject them to suitable treatment.
PMID- 28694628
TI - Advanced Magnetic Resonance Imaging of Glioblastoma Multiforme.
PMID- 28694629
TI - Acute Disseminated Encephalomyelitis Presenting as an Isolated Mesodiencephalic
Junction Lesion.
PMID- 28694630
TI - Mood Disorder as an Early Presentation of Epidermoid of Quadrigeminal Cistern.
AB - Intracranial epidermoids are space-occupying lesions of rare variant. Although
cerebropontine angle and parasellar region are common sites of occurrence, it has
been reported in various other parts of the intracranial cavity. Headache and
features of increased intracranial tension are the common clinical manifestation.
Report of psychiatric symptoms as the initial presentation of epidermoid is not
known in literature except a single case report, which describes mutism to be the
manifestation of intracranial epidermoid. We present here the case of a young
male, who presented with long depressive episode persisting for 3 years with
subsequent switch to mania, which persisted for more than 3 years. An episode of
unconsciousness warranted neuroimaging, which revealed a large epidermoid of the
quadrigeminal cistern. Surgical resection of the epidermoid was done. Persisting
mood symptoms had responded to mood stabilizer and antipsychotic treatment.
PMID- 28694631
TI - Commentary.
PMID- 28694632
TI - Late-onset Familial Amyloidotic Polyneuropathy with Bence Jones Proteinuria and
Cardiomyopathy.
AB - Familial amyloidotic polyneuropathy is a genetically determined disease
characterized by deposition of an anomalous transthyretin. A high index of
suspicion is needed for this multisymptomatic and lethal disease to be diagnosed.
The patient was a 70-year-old male examined due to hypesthesia in the hands and
feet, plus difficulty walking. A neurophysiological study delivered the diagnosis
of axonal sensorimotor polyneuropathy. He later developed cardiac symptoms and
diarrhea. Urine laboratory analyses revealed a monoclonal spike of light chains
(kappa). Biopsies of abdominal fat and bone marrow yielded normal results. The
genetic study was compatible with a heterozygous Val30Met-transthyretin mutation.
Very few case studies have described an association between familial amyloidotic
polyneuropathy and monoclonal gammopathy. We stress that genetic confirmation is
important regardless of the type of amyloid deposition revealed by the biopsy.
PMID- 28694633
TI - Facial Diplegia as Initial Manifestation of Acute, Myelomonocytic Leukemia with
Isolated Trisomy 47, XY,+11[14]/46, XY[6].
AB - Bilateral peripheral facial palsy (facial diplegia) has been repeatedly reported
as a neurologic manifestation of acute myeloid leukemia but has not been reported
as the initial clinical manifestation of myelomonocytic leukemia. A 71-year-old
male developed left-sided peripheral facial palsy being interpreted and treated
as Bell's palsy. C-reactive protein (CRP) and leukocyte count 4 days later were
2.5 mg/l and 16 G/l, respectively. Steroids were ineffective. Seven days after
onset, he developed right-sided peripheral facial palsy. Three days later, CRP
and leukocyte count were 234.3 mg/l and 59.5 G/l, respectively. Cerebrospinal
fluid investigations revealed pleocytosis (62/3) and elevated protein (54.9
mg/dl). Two days later, pleocytosis and leukocytosis were attributed to
myelomonocytic leukemia. Leukemic meningeosis was treated with cytarabine and
methotrexate intrathecally. In addition, cytarabine and idarubicin were applied
intravenously. Under this regimen, facial diplegia gradually improved. Facial
diplegia may be the initial clinical manifestation of myelomonocytic leukemia,
facial diplegia obligatorily requires lumbar puncture, and unilateral peripheral
facial palsy is not always Bell's palsy. Patients with alleged unilateral Bell's
palsy and slightly elevated leukocytes require close follow-up and more extensive
investigations than patients without abnormal blood tests.
PMID- 28694634
TI - Junctional Chiasmatic Syndrome Due to Large Anterior Communicating Artery
Aneurysm.
AB - Even though aneurysm involving the anterior communicating artery (A Com A) was
common in clinical practice, producing compressive symptoms such as visual loss
was rare. We report a case, in which patient had gradually progressive visual
loss with features of the junctional chiasmatic syndrome, imaging revealed
partially thrombosed large A Com A aneurysm. Intraoperatively, aneurysm was found
compressing the optic chiasm and right optic nerve, following clipping and
decompression of the optic nerve and chiasm there was gradually improvement in
the vision over 2 weeks postoperatively.
PMID- 28694635
TI - Symptomatic Vertebral Hemangioma in a Young Child.
AB - Vertebral hemangiomas (VHs) are the most common benign vertebral neoplasm and
typically are asymptomatic, only to be discovered incidentally on imaging from
the fourth to fifth decade of life. Seldom do they enlarge to a point of
compression, causing pain and focal neurologic deficits. We present the rare case
of an 8-year-old female who presented with paraparesis after a fall. Imaging
revealed a pathological fracture of the T8 vertebra with retropulsion and spinal
cord compression from both fracture and epidural tumor tissue. The patient
underwent an anterior and posterior removal of the tumor, decompression, and
fusion. Pathological report of specimen biopsy confirmed a benign hemangioma. To
the best of our knowledge, this is the same age as the youngest previously
reported case of symptomatic VH and it is the longest to be recurrence-free at
follow-up. The hemangioma was successfully treated with tumor removal,
decompression, and fusion. No adjuvant treatment was required, and she remained
asymptomatic without recurrence at her 4-year follow-up.
PMID- 28694636
TI - Delayed Facial Palsy after Microvascular Decompression: Report of Two Cases.
AB - Microvascular decompression (MVD) is a novel surgical procedure predominantly
performed for treating trigeminal neuralgia (TN) and hemifacial spasm (HS).
Multiple studies have proven the long-term success of MVD for both these
conditions. The most common complications of MVD reported include chemical
meningitis, facial hypesthesia, cerebrospinal fluid leak, facial paresis, and
hearing loss. Delayed facial palsy (DFP) is an uncommon complication mostly noted
in MVD for HS and after the removal of acoustic tumors. We report two cases of
DFP occurring after performing MVD, one each for HS and TN. This is also the
first case of DFP to be reported after MVD for TN. Both were young females who
developed DFP 2 weeks after surgery. They were managed with oral steroids and
acyclovir for 2-3 weeks and achieved excellent outcome at an average of 4.5 weeks
from the onset. We conclude that although majority of the cases improve
spontaneously, steroids and acyclovir might assist in faster recovery.
PMID- 28694637
TI - Isolated Intracranial Myeloid Sarcoma Occurring as Relapse in Acute Myeloid
Leukemia.
AB - Myeloid sarcoma (MS) or chloroma is a rare extramedullary tumor composed of
extramedullary proliferation of blasts of granulocytic, monocytic, erythroid, or
megakaryocytic lineage occurring at sites outside the bone marrow. MS occurs in
2%-8% of patients with acute myeloid leukemia (AML), sometimes it occurs as the
presenting manifestation of relapse in a patient in remission. We describe the
case of a young male with AML in remission for 6 years presenting with central
nervous system symptoms. Magnetic resonance imaging showed an extra-axial altered
intensity lesion in the parasagittal parietal region, infiltrating
anterosuperiorly into anterior falx, and posterosuperior aspect of the superior
sagittal sinus. A biopsy from the lesion was diagnostic of MS which was positive
for myeloperoxidase. He did not have any other sites of disease. He has received
chemotherapy with FLAG (Fludarabine, Cytosine arabinoside) followed by cranial
irradiation and is in complete remission.
PMID- 28694638
TI - Predicting Prognosis of Psychosis in Huntington's Disease: Case Report and Review
of Literature.
AB - Huntington's disease (HD) is rare variant of progressive neurodegenerative
disorder which follows an autosomal dominant pattern. Psychiatric comorbidities
are not uncommon with HD. Mood disorder, cognitive disturbances, anxiety
disorders, and psychosis are the psychiatric comorbidities reported with HD. We
report here a case of HD, where psychosis developed during illness. Prognosis of
psychosis in HD is emphasized in this report with review of literature.
PMID- 28694639
TI - Primary Paraspinal Hydatidosis Causing Acute Paraplegia.
AB - The zoonotic infection hydatidosis is caused by the tapeworm cestode,
Echinococcus granulosus. Though considered endemic in India where association of
humans with sheep and dogs form part of the livelihood, primary skeletal muscle
involvement of the disease is an extremely rare event. We report a case of
primary paraspinal hydatidosis with extradural extension causing acute
paraplegia. Excision of the cyst and decompression of the cord was done along
with albendazole therapy. Paraspinal hydatid disease is a rare entity, and in
regions where hydatid disease is endemic, it can be involved in the differential
diagnosis of acute compressive myelopathy. Although antihelminthic chemotherapy
forms the mainstay of the treatment, surgical intervention forms a major part of
the management.
PMID- 28694640
TI - Guillain-Barre Syndrome in Postpartum Period: Rehabilitation Issues and Outcome -
Three Case Reports.
AB - We report three females who developed Guillain-Barre Syndrome in postpartum
period (within 6 weeks of delivery) and were admitted in the Neurological
Rehabilitation Department for rehabilitation after the initial diagnosis and
treatment in the Department of Neurology. The first case, axonal variant (acute
motor axonal neuropathy [AMAN]) had worst presentation at the time of admission,
recovered well by the time of discharge. The second case, acute motor sensory
axonal neuropathy variant and the third case, AMAN variant presented at the late
postpartum period. Medical treatment was sought much later due to various reasons
and both the patients had an incomplete recovery at discharge. Apart from their
presentations, rehabilitation management is also discussed in some detail.
PMID- 28694641
TI - Medicine Revisited: Safeguard Yourself against "Oblivious to the Obvious".
PMID- 28694642
TI - Cerebellar Cystic Oligodendroglioma in a Young Adult.
PMID- 28694643
TI - Anterior Pituitary Hormonal Disturbances in Patients Suffering with Traumatic
Brain Injury.
PMID- 28694644
TI - Venous Air Embolism During Removal of Bony Spur in a Child of Split Cord
Malformation.
PMID- 28694645
TI - Using of Open Biopsy Microseparator in the Fresh Cadaveric Cow Brain for the
Evaluation of Clinical Usability.
PMID- 28694646
TI - Afebrile Seizures as Initial Symptom of Hypocalcemia Secondary to
Hypoparathyroidism.
PMID- 28694647
TI - Headache, Facial Palsy, and Diplopia: An Unusual Presentation of Ruptured Distal
Anterior Cerebral Artery Aneurysm.
PMID- 28694648
TI - Photosensitive Posthypoxic Reflex Myoclonus in a Postcardiac Arrest Individual:
An Interesting Finding.
PMID- 28694649
TI - Paraganglioma of the Filum Terminale: An Extremely Uncommon Neuroendocrine
Neoplasm Located in Spine.
PMID- 28694650
TI - Suboccipital Extraspinal Extracranial Atypical Teratoid Rhabdoid Tumor.
PMID- 28694651
TI - How to Improve Adherence to Medication and Follow-up in Chronic Mental Illnesses:
Stakeholder Views.
PMID- 28694652
TI - Pontine Hemorrhage Causing Bilateral Hypertrophic Olivary Degeneration.
PMID- 28694653
TI - Attenuated adenomatous polyposis of the large bowel: Present and future.
AB - Attenuated adenomatous polyposis (AAP) is a poorly understood syndrome, that can
be defined as the presence of 10-99 synchronous adenomas in the large bowel, and
it is considered a phenotypic variant of familial adenomatous polyposis (FAP).
This definition has the advantage of simplicity, but it may include sporadic
multiple adenomas of the large bowel at an extreme, or FAP cases on the other
side. AAP shows a milder phenotype than FAP, with an older age of onset of
adenomas and cancer, and less frequent extracolonic manifestations. AAP may be
diagnosed as a single case in a family or, less frequently, it may be present in
other family members, and it shows distinct pattern of inheritance. In less than
50% of cases, it may be caused by adenomatous polyposis coli (APC) or MUTYH
mutations, referred to as APC-associated polyposis, inherited as an autosomal
dominant trait, or MUTYH-associated polyposis, which shows an autosomal recessive
mechanism of inheritance, respectively. Surveillance should rely on colonoscopy
at regular intervals, with removal of adenomas and careful histological
examination. When removal of polyps is not possible or advanced lesions are
observed, the surgical approach is mandatory, being subtotal colectomy with ileo
rectal anastomosis the treatment of choice. Studies on this syndrome are lacking,
and controversies are still present on many issues, thus, other clinical and
genetic studies are requested.
PMID- 28694654
TI - Evolution of associating liver partition and portal vein ligation for staged
hepatectomy: Simpler, safer and equally effective methods.
AB - Associating liver partition and portal vein ligation for staged hepatectomy
(ALPPS) has been recently demonstrated as a method to induce rapid and extensive
hypertrophy within a short time and has been employed for a variety of primary
and metastatic liver tumors. However, controversies remain due to its high
morbidity and mortality. To enable safer surgery, liver surgeons have searched
for better technical modifications, such as partial ALPPS, mini-ALPPS, minimally
invasive ALPPS, and Terminal branches portal vein Embolization Liver Partition
for Planned hepatectomy (TELPP). It seems that TELPP is very promising, because
it has the main advantage of ALPPS - the rapid increase of future liver remnant
volume, but the morbidity and mortality are much lower because only one surgical
operation is required.
PMID- 28694655
TI - Antioxidant dietary approach in treatment of fatty liver: New insights and
updates.
AB - Non-alcoholic fatty liver disease (NAFLD) is a common clinicopathological
condition, encompassing a range of conditions caused by lipid deposition within
liver cells. To date, no approved drugs are available for the treatment of NAFLD,
despite the fact that it represents a serious and growing clinical problem in the
Western world. Identification of the molecular mechanisms leading to NAFLD
related fat accumulation, mitochondrial dysfunction and oxidative balance
impairment facilitates the development of specific interventions aimed at
preventing the progression of hepatic steatosis. In this review, we focus our
attention on the role of dysfunctions in mitochondrial bioenergetics in the
pathogenesis of fatty liver. Major data from the literature about the
mitochondrial targeting of some antioxidant molecules as a potential treatment
for hepatic steatosis are described and critically analysed. There is ample
evidence of the positive effects of several classes of antioxidants, such as
polyphenols (i.e., resveratrol, quercetin, coumestrol, anthocyanins,
epigallocatechin gallate and curcumin), carotenoids (i.e., lycopene, astaxanthin
and fucoxanthin) and glucosinolates (i.e., glucoraphanin, sulforaphane, sinigrin
and allyl-isothiocyanate), on the reversion of fatty liver. Although the
mechanism of action is not yet fully elucidated, in some cases an indirect
interaction with mitochondrial metabolism is expected. We believe that such
knowledge will eventually translate into the development of novel therapeutic
approaches for fatty liver.
PMID- 28694656
TI - Helicobacter pylori BabA in adaptation for gastric colonization.
AB - Helicobacter pylori (H. pylori) as a causative agent of gastric complications, is
well adapted for the colonization of gastric mucosa. Although the infectious
process depends on several factors, the adhesion to the gastric mucosa is the
first and important step. Among several outer membrane proteins, BabA is one of
the significant protein involving in many inflammatory processes in addition to
its role in the attachment for the persistent colonization. We performed a PubMed
search using the key words: "babA", "pylori", "gastric complications",
"homologous recombination", "slipped strand mispairing"; a total of 249 articles
were displayed. Of these we mainly focused on articles with the full text in
English and published between 2005 and 2016. H. pylori BabA is involved in
binding with receptors; however, its synthesis is regulated by phase variation.
In this review we confirm that H. pylori babA can be modulated at the molecular
and functional levels to adapt to the stress within the gastro-intestinal tract.
PMID- 28694657
TI - Advances in surgical management for locally recurrent rectal cancer: How far have
we come?
AB - Locally recurrent rectal cancer (LRRC) is a complex disease with far-reaching
implications for the patient. Until recently, research was limited regarding
surgical techniques that can increase the ability to perform an en bloc resection
with negative margins. This has changed in recent years and therefore outcomes
for these patients have improved. Novel radical techniques and adjuncts allow for
more radical resections thereby improving the chance of negative resection
margins and outcomes. In the past contraindications to surgery included anterior
involvement of the pubic bone, sacral invasions above the level of S2/S3 and
lateral pelvic wall involvement. However, current data suggests that previously
unresectable cases may now be feasible with novel techniques, surgical approaches
and reconstructive surgery. The publications to date have only reported small
patient pools with the research conducted by highly specialised units. Moreover,
the short and long-term oncological outcomes are currently under review.
Therefore although surgical options for LRRC have expanded significantly, one
should balance the treatment choices available against the morbidity associated
with the procedure and select the right patient for it.
PMID- 28694658
TI - Anti-steatotic and anti-fibrotic effects of the KCa3.1 channel inhibitor,
Senicapoc, in non-alcoholic liver disease.
AB - AIM: To evaluate a calcium activated potassium channel (KCa3.1) inhibitor
attenuates liver disease in models of non-alcoholic fatty liver disease (NAFLD).
METHODS: We have performed a series of in vitro and in vivo studies using the
KCa3.1 channel inhibitor, Senicapoc. Efficacy studies of Senicapoc were conducted
in toxin-, thioacetamide (TAA) and high fat diet (HFD)-induced models of liver
fibrosis in rats. Efficacy and pharmacodynamic effects of Senicapoc was
determined through biomarkers of apoptosis, inflammation, steatosis and fibrosis.
RESULTS: Upregulation of KCa3.1 expression was recorded in TAA-induced and high
fat diet-induced liver disease. Treatment with Senicapoc decreased palmitic acid
driven HepG2 cell death. (P < 0.05 vs control) supporting the finding that
Senicapoc reduces lipid-driven apoptosis in HepG2 cell cultures. In animals fed a
HFD for 6 wk, co-treatment with Senicapoc, (1) reduced non-alcoholic fatty liver
disease (NAFLD) activity score (NAS) (0-8 scale), (2) decreased steatosis and (3)
decreased hepatic lipid content (Oil Red O, P < 0.05 vs vehicle). Randomization
of TAA animals and HFD fed animals to Senicapoc was associated with a decrease in
liver fibrosis as evidenced by hydroxyproline and Masson's trichrome staining (P
< 0.05 vs vehicle). These results demonstrated that Senicapoc mitigates both
steatosis and fibrosis in liver fibrosis models. CONCLUSION: These data suggest
that Senicapoc interrupts more than one node in progressive fatty liver disease
by its anti-steatotic and anti-fibrotic activities, serving as a double-edged
therapeutic sword.
PMID- 28694659
TI - Induction of chronic cholestasis without liver cirrhosis - Creation of an animal
model.
AB - AIM: To analyze time intervals of inflammation and regeneration in a cholestatic
rat liver model. METHODS: In 36 Lewis rats, divided into six groups of 6 animals
(postoperative observation periods: 1, 2, 3, 4, 6, 8 wk), the main bile duct was
ligated with two ligatures and observed for the periods mentioned above. For
laboratory evaluation, cholestasis parameters (bilirubin, gamma-GT), liver cell
parameters (ASAT, ALAT) and liver synthesis parameters (quick, albumin) were
determined. For histological analysis, HE, EvG, ASDCL and HMGB-1 stainings were
performed. Furthermore, we used the mRNA of IL-33, GADD45a and p-21 for analyzing
cellular stress and regeneration in cholestatic rats. RESULTS: In chemical
laboratory and histological evaluation, a distinction between acute and chronic
cholestatic liver injury with identification of inflammation and regeneration
could be demonstrated by an increase in cholestasis (bilirubin: 1-wk group,
156.83 +/- 34.12 MUmol/L, P = 0.004) and liver cell parameters (ASAT: 2-wk group,
2.1 +/- 2.19 MUmol/L.s, P = 0.03; ALAT: 2-wk group, 1.03 +/- 0.38 MUmol/L.s, P =
0.03) after bile duct ligation (BDL). Histological evaluation showed an increase
of bile ducts per portal field (3-wk group, 48 +/- 6.13, P = 0.004) during the
first four weeks after bile duct ligation. In addition to inflammation, which is
an expression of acute cholestasis, there was an increase of necrotic areas in
the histological sections (2-wk group, 1.38% +/- 2.28% per slide, P = 0.002).
Furthermore, the inflammation could be verified by ASDCL (4-wk group, 22 +/- 5.93
positive cells per portal field, P = 0.041) and HMGB-1 [2-wk group, 13 +/- 8.18
positive cells per field of view (FoV), P = 0.065] staining. Therefore, in
summary of the laboratory evaluation and histological studies, acute cholestasis
could be found during the first four weeks after bile duct ligation.
Subsequently, the described parameters declined so that chronic cholestasis could
be assumed. For quantification of secondary biliary cirrhosis, eosin staining was
performed, which did not reveal any signs of liver remodeling, thus precluding
the development of a chronic cholestasis model. Additionally, to establish the
chronic cholestasis model, we evaluated liver regeneration capacity through
measurements of IL-33, p-21 and GADD45a mRNA. CONCLUSION: We created a chronic
cholestasis model. The point of inflammatory and regenerative balance was reached
after four weeks. This finding should be used for experimental approaches dealing
with chronic cholestatic liver damage.
PMID- 28694660
TI - Solid lipid nanoparticles delivering anti-inflammatory drugs to treat
inflammatory bowel disease: Effects in an in vivo model.
AB - AIM: To improve anti-inflammatory activity while reducing drug doses, we
developed a nanoformulation carrying dexamethasone and butyrate. METHODS:
Dexamethasone cholesteryl butyrate-solid lipid nanoparticles (DxCb-SLN) were
obtained with the warm microemulsion method. The anti-inflammatory activity of
this novel nanoformulation has been investigated in vitro (cell adhesion to human
vascular endothelial cells and pro-inflammatory cytokine release by
lipopolysaccharide-induced polymorphonuclear cells) and in vivo (disease activity
index and cytokine plasma concentrations in a dextran sulfate sodium-induced
mouse colitis) models. Each drug was also administered separately to compare its
effects with those induced by their co-administration in SLN at the same
concentrations. RESULTS: DxCb-SLN at the lowest concentration tested (Dx 2.5
nmol/L and Cb 0.1 MUmol/L) were able to exert a more than additive effect
compared to the sum of the individual effects of each drug, inducing a
significant in vitro inhibition of cell adhesion and a significant decrease of
pro-inflammatory cytokine (IL-1beta and TNF-alpha) in both in vitro and in vivo
models. Notably, only the DxCb nanoformulation administration was able to achieve
a significant cytokine decrease compared to the cytokine plasma concentration of
the untreated mice with dextran sulfate sodium-induced colitis. Specifically,
DxCb-SLN induced a IL-1beta plasma concentration of 61.77% +/- 3.19%, whereas Dx
or Cb used separately induced a concentration of 90.0% +/- 2.8% and 91.40% +/-
7.5%, respectively; DxCb-SLN induced a TNF-alpha plasma concentration of 30.8% +/
8.9%, whereas Dx or Cb used separately induced ones of 99.5% +/- 4.9% and 71.1%
+/- 10.9%, respectively. CONCLUSION: Our results indicate that the co
administration of dexamethasone and butyrate by nanoparticles may be beneficial
for inflammatory bowel disease treatment.
PMID- 28694661
TI - Relevance of proteolysis and proteasome activation in fatty liver graft
preservation: An Institut Georges Lopez-1 vs University of Wisconsin appraisal.
AB - AIM: To compare liver proteolysis and proteasome activation in steatotic liver
grafts conserved in University of Wisconsin (UW) and Institut Georges Lopez-1
(IGL-1) solutions. METHODS: Fatty liver grafts from male obese Zucker rats were
conserved in UW and IGL-1 solutions for 24 h at 4 degrees Cand subjected to "ex
vivo" normo-thermic perfusion (2 h; 37 degrees C). Liver proteolysis in tissue
specimens and perfusate was measured by reverse-phase high performance liquid
chromatography. Total free amino acid release was correlated with the activation
of the ubiquitin proteasome system (UPS: measured as chymotryptic-like activity
and 20S and 19S proteasome), the prevention of liver injury (transaminases),
mitochondrial injury (confocal microscopy) and inflammation markers (TNF 1 alpha,
high mobility group box-1 (HGMB-1) and PPAR gamma), and liver apoptosis (TUNEL
assay, cytochrome c and caspase 3). RESULTS: Profiles of free AA (alanine,
proline, leucine, isoleucine, methionine, lysine, ornithine, and threonine, among
others) were similar for tissue and reperfusion effluent. In all cases, the IGL-1
solution showed a significantly higher prevention of proteolysis than UW (P <
0.05) after cold ischemia reperfusion. Livers conserved in IGL-1 presented more
effective prevention of ATP-breakdown and more inhibition of UPS activity
(measured as chymotryptic-like activity). In addition, the prevention of liver
proteolysis and UPS activation correlated with the prevention of liver injury
(AST/ALT) and mitochondrial damage (revealed by confocal microscopy findings) as
well as with the prevention of inflammatory markers (TNF1alpha and HMGB) after
reperfusion. In addition, the liver grafts preserved in IGL-1 showed a
significant decrease in liver apoptosis, as shown by TUNEL assay and the
reduction of cytochrome c, caspase 3 and P62 levels. CONCLUSION: Our comparison
of these two preservation solutions suggests that IGL-1 helps to prevent ATP
breakdown more effectively than UW and subsequently achieves a higher UPS
inhibition and reduced liver proteolysis.
PMID- 28694662
TI - Naturally occurring mutations in the reverse transcriptase region of hepatitis B
virus polymerase from treatment-naive Korean patients infected with genotype C2.
AB - AIM: To report naturally occurring mutations in the reverse transcriptase region
(RT) of hepatitis B virus (HBV) polymerase from treatment naive Korean chronic
patients infected with genotype C2. METHODS: Here, full-length HBV reverse
transcriptase RT sequences were amplified and sequenced from 131 treatment naive
Korean patients chronically infected with hepatitis B genotype C2. The patients
had two distinct clinical statuses: 59 patients with chronic hepatitis (CH) and
72 patients with hepatocellular carcinoma (HCC). The deduced amino acids (AAs) at
42 previously reported potential nucleos(t)ide analog resistance (NAr) mutation
positions in the RT region were analyzed. RESULTS: Potential NAr mutations
involving 24 positions were found in 79 of the 131 patients (60.3%). Notably, AA
substitutions at 2 positions (rt184 and rt204) involved in primary drug
resistance and at 2 positions (rt80 and rt180) that functioned as
secondary/compensatory mutations were detected in 10 patients (1 CH patient and 9
HCC patients) and 7 patients (1 CH and 6 HCC patients), respectively. The overall
mutation frequencies in the HCC patients (3.17%, 96/3024 mutations) were
significantly higher than the frequencies in the CH patients (2.09%, 52/2478
mutations) (P = 0.003). In addition, a total of 3 NAr positions, rt80, rt139 and
rt204 were found to be significantly related to HCC from treatment naive Korean
patients. CONCLUSION: Our data showed that naturally occurring NAr mutations in
South Korea might contribute to liver disease progression (particularly HCC
generation) in chronic patients with genotype C2 infections.
PMID- 28694663
TI - Inhibition of N-methyl-N-nitrosourea-induced gastric tumorigenesis by Liuwei
Dihuang Pill in db/db mice.
AB - AIM: To investigate the inhibitory effect of Liuwei Dihuang Pill (LDP) on gastric
tumorigenesis induced by N-methyl-N-nitrosourea (MNU) in diabetic mice. METHODS:
Four-week-old mice were divided into four groups: A, 12 db/m mice treated with
MNU and saline, as the non-diabetic control; B, 12 db/db mice treated with MNU
and saline, as the diabetic control; C, 12 db/db mice treated with MNU and
metformin, as the positive control; and D, 12 db/db mice treated with MNU and
LDP. MNU was administrated for 20 wk to induce gastric carcinogenesis. LDP was
administrated for 10 wk for improvement of insulin resistance. Body weight and
food intake were measured every week. Blood samples were collected for assays of
fasting blood glucose, insulin, insulin-like growth factor (IGF)-1, adiponectin
and leptin. Stomach tissues were collected for histopathological analysis,
immunohistochemical staining of Ki67, quantitative reverse transcription
polymerase chain reaction and western blotting. RESULTS: The incidence of MNU
induced gastric dysplasia was significantly elevated in diabetic (db/db) mice
relative to the control (db/m) mice. The incidence of gastric dysplasia was
significantly reduced by LDP with suppression of cell proliferation, as
demonstrated by a decrease in Ki67 staining. Hyperglycemia, hyperinsulinemia and
serum IGF-1 were inhibited by LDP. Expression of IGF-1 and insulin receptor mRNAs
was decreased, phosphorylation of IGF-1 receptor and AKT protein was reduced in
the stomach tissues by LDP. In addition, adiponectin was increased and leptin was
decreased in the serum by LDP. CONCLUSION: LDP decreased risk of gastric
dysplasia in type 2 diabetic mice by down-regulation of IGF and insulin activity
and correction of adipokines disorders.
PMID- 28694664
TI - miR-382 functions as a tumor suppressor against esophageal squamous cell
carcinoma.
AB - AIM: To explore the effect of miR-382 on esophageal squamous cell carcinoma
(ESCC) in vitro and its possible molecular mechanism. METHODS: Eca109 cells
derived from human ESCC and Het-1A cells derived from human normal esophageal
epithelium were used. Lentivirus-mediated miR-382 was overexpressed in Eca109
cells. The effect of miR-382 on cell proliferation was evaluated by MTT and
colony formation assay. For cell cycle analysis, cells were fixed and stained for
30 min with propidium iodide (PI) staining buffer containing 10 mg/mL PI and 100
mg/mL RNase A, and analyzed by BD FACSCaliburTM flow cytometer. For cell
apoptosis assay, cells were stained with an Annexin V-FITC/PI Apoptosis Detection
Kit according to the manufacturer's instructions and analyzed by a dual-laser
flow cytometer. Cell invasion and migration abilities were determined through use
of transwell chambers, non-coated or pre-coated with matrigel. Levels of proteins
related to cell growth and migration were examined by western blotting. RESULTS:
Endogenous miR-382 was down-regulated in Eca109 cells compared with Het-1A.
Introduction of miR-382 not only significantly inhibited proliferation and colony
formation, but also arrested cell cycle at the G2/M phase, as well as promoted
apoptosis and autophagy in Eca109 cells. Migration, invasion and epithelial
mesenchymal transition of Eca109 cells were suppressed by overexpressing miR-382.
Western blotting results showed that miR-382 inhibited the phosphorylation of
mTOR and 4E-BP1. CONCLUSION: miR-382 functions as a tumor suppressor against ESCC
development and metastasis, and could be considered as a potential drug source
for the treatment of ESCC patients.
PMID- 28694665
TI - Pancreas preserving distal duodenectomy: A versatile operation for a range of
infra-papillary pathologies.
AB - AIM: To investigate the range of pathologies treated by pancreas preserving
distal duodenectomy (PPDD) and present the outcome of follow-up. METHODS:
Neoplastic lesions of the duodenum are treated conventionally by
pancreaticoduodenectomy. Lesions distal to the major papilla may be suitable for
a pancreas-preserving distal duodenectomy, potentially reducing morbidity and
mortality. We present our experience with this procedure. Selective
intraoperative duodenoscopy assessed the relationship of the papilla to the
lesion. After duodenal mobilisation and confirmation of the site of the lesion,
the duodenum was transected distal to the papilla and beyond the duodenojejunal
flexure and a side-to-side duodeno-jejunal anastomosis was formed. Patients were
identified from a prospectively maintained database and outcomes determined from
digital health records with a dataset including demographics, co-morbidities,
mode of presentation, preoperative imaging and assessment, nutritional support
needs, technical operative details, blood transfusion requirements, length of
stay, pathology including lymph node yield and lymph node involvement, length of
follow-up, complications and outcomes. Related published literature was also
reviewed. RESULTS: Twenty-four patients had surgery with the intent of performing
PPDD from 2003 to 2016. Nineteen underwent PPDD successfully. Two patients
planned for PPDD proceeded to formal pancreaticoduodenectomy (PD) while three had
unresectable disease. Median post-operative follow-up was 32 mo. Pathologies
resected included duodenal adenocarcinoma (n = 6), adenomas (n = 5),
gastrointestinal stromal tumours (n = 4) and lipoma, bleeding duodenal
diverticulum, locally advanced colonic adenocarcinoma and extrinsic compression
(n = 1 each). Median postoperative length of stay (LOS) was 8 d and morbidity was
low [pain and nausea/vomiting (n = 2), anastomotic stricture (n = 1), pneumonia
(n = 1), and overwhelming post-splenectomy sepsis (n = 1, asplenic patient)].
PPDD was associated with a significantly shorter LOS than a contemporaneous PD
series [PPDD 8 (6-14) d vs PD 11 (10-16) d, median (IQR), P = 0.026]. The 30-d
mortality was zero and 16 of 19 patients are alive to date. One patient died of
recurrent duodenal adenocarcinoma 18 mo postoperatively and two died of unrelated
disease (at 2 mo and at 8 years respectively). CONCLUSION: PPDD is a versatile
operation that can provide definitive treatment for a range of duodenal
pathologies including adenocarcinoma.
PMID- 28694666
TI - Clinical importance of colonoscopy in patients with gastric neoplasm undergoing
endoscopic submucosal dissection.
AB - AIM: To evaluate the usefulness of total colonoscopy (TCS) for patients
undergoing gastric endoscopic submucosal dissection (ESD) and to assess risk
factors for colorectal neoplasms. METHODS: Of the 263 patients who underwent ESD
at our department between May 2010 and December 2013, 172 patients undergoing TCS
during a one-year period before and after ESD were targeted. After excluding
patients with a history of surgery or endoscopic therapy for colorectal
neoplasms, 158 patients were analyzed. Of the 868 asymptomatic patients who
underwent TCS during the same period because of positive fecal immunochemical
test (FIT) results, 158 patients with no history of either surgery or endoscopic
therapy for colorectal neoplasms who were matched for age and sex served as the
control group for comparison. RESULTS: TCS revealed adenoma less than 10 mm in 53
patients (33.6%), advanced adenoma in 17 (10.8%), early colorectal cancer in 5
(3.2%), and advanced colorectal cancer in 4 (2.5%). When the presence or absence
of adenoma less than 10 mm, advanced adenoma, and colorectal cancer and the
number of adenomas were compared between patients undergoing ESD and FIT-positive
patients, there were no statistically significant differences in any of the
parameters assessed. The patients undergoing ESD appeared to have the same risk
of colorectal neoplasms as the FIT-positive patients. Colorectal neoplasms were
clearly more common in men than in women (P = 0.031). Advanced adenoma and cancer
were significantly more frequent in patients with at least two of the following
conditions: hypertension, dyslipidemia, and diabetes mellitus (P = 0.019).
CONCLUSION: In patients undergoing gastric ESD, TCS appears to be important for
detecting synchronous double neoplasms. Advanced adenoma and cancer were more
common in patients with at least two of the following conditions: hypertension,
dyslipidemia, and diabetes mellitus. Caution is therefore especially warranted in
patients with these risk factors.
PMID- 28694667
TI - Outcomes of right-lobe and left-lobe living-donor liver transplantations using
small-for-size grafts.
AB - AIM: To analyze the outcomes of living-donor liver transplantation (LDLT) using
left-lobe (LL) or right-lobe (RL) small-for-size (SFS) grafts. METHODS:
Prospectively collected data of adult patients who underwent LDLT at our hospital
in the period from January 2003 to December 2013 were reviewed. The patients were
divided into the RL-LDLT group and the LL-LDLT group. The two groups were
compared in terms of short- and long-term outcomes, including incidence of
postoperative complication, graft function, graft survival, and patient survival.
A SFS graft was defined as a graft with a ratio of graft weight (GW) to recipient
standard liver volume (RSLV) (GW/RSLV) of < 50%. The Urata formula was used to
estimate RSLV. RESULTS: Totally 218 patients were included for analysis, with 199
patients in the RL-LDLT group and 19 patients in the LL-LDLT group. The two
groups were similar in terms of age (median, 53 years in the RL-LDLT group and 52
years in the LL-LDLT group, P = 0.997) but had significantly different ratios of
men to women (165:34 in the RL-LDLT group and 8:11 in the LL-LDLT group, P <
0.0001). The two groups were also significantly different in GW (P < 0.0001),
GW/RSLV (P < 0.0001), and graft cold ischemic time (P = 0.007). When it comes to
postoperative complication, the groups were comparable (P = 0.105). Five patients
died in hospital, 4 (2%) in the RL-LDLT group and 1 (5.3%) in the LL-LDLT group
(P = 0.918). There were 38 graft losses, 33 (16.6%) in the RL-LDLT group and 5
(26.3%) in the LL-LDLT group (P = 0.452). The 5-year graft survival rate was
significantly better in the RL-LDLT group (95.2% vs 89.5%, P = 0.049). The two
groups had similar 5-year patient survival rates (RL-LDLT: 86.8%, LL-LDLT: 89.5%,
P = 0.476). CONCLUSION: The use of SFS graft in LDLT requires careful tailor-made
surgical planning and meticulous operation. LL-LDLT can be a good alternative to
RL-LDLT with similar recipient outcomes but a lower donor risk. Further research
into different patient conditions is needed in order to validate the use of LL
graft.
PMID- 28694668
TI - Potential application of neogalactosylalbumin in positron emission tomography
evaluation of liver function.
AB - AIM: To investigate the evaluation of neogalactosylalbumin (NGA) for liver
function assessment based on positron emission tomography technology. METHODS:
Female Kunming mice were assigned randomly to two groups: fibrosis group and
normal control group. A murine hepatic fibrosis model was generated by
intraperitoneal injection of 10% carbon tetrachloride (CCl4) at 0.4 mL every 48 h
for 42 d. 18F-labeled NGA ([18F]FNGA) was synthesized and administered at a
dosage of 3.7 MBq/mouse to both fibrosis mice and normal control mice.
Distribution of [18F]FNGA amongst organs was examined, and dynamic scanning was
performed. Parameters were set up to compare the uptake of tracers by fibrotic
liver and healthy liver. Serologic tests for liver function were also performed.
RESULTS: The liver function of the fibrosis model mice was significantly impaired
by the use of CCl4. In the fibrosis model mice, hepatic fibrosis was verified by
naked eye assessment and pathological analysis. [18F]FNGA was found to
predominantly accumulate in liver and kidneys in both control group (n = 21) and
fibrosis group (n = 23). The liver uptake ability (LUA), peak time (Tp), and
uptake rate (LUR) of [18F]FNGA between healthy liver (n = 8) and fibrosis liver
(n = 10) were significantly different (P < 0.05, < 0.01, and < 0.05,
respectively). LUA was significantly correlated with total serum protein level
(TP) (P < 0.05). Tp was significantly correlated with both TP and glucose (Glu)
concentration (P < 0.05 both), and LUR was significantly correlated with both
total bile acid and Glu concentration (P < 0.01 and < 0.05, respectively).
CONCLUSION: [18F]FNGA mainly accumulated in liver and remained for sufficient
time. Functionally-impaired liver showed a significant different uptake pattern
of [18F]FNGA compared to the controls.
PMID- 28694669
TI - Magnetic resonance imaging may predict deep remission in patients with perianal
fistulizing Crohn's disease.
AB - AIM: To evaluate the imaging course of Crohn's disease (CD) patients with
perianal fistulas on long-term maintenance anti-tumor necrosis factor (TNF)-alpha
therapy and identify predictors of deep remission. METHODS: All patients with
perianal CD treated with anti-TNF-alpha therapy at our tertiary care center were
evaluated by magnetic resonance imaging (MRI) and clinical assessment. Two MR
examinations were performed: at initiation of anti-TNF-alpha treatment and then
at least 2 years after. Clinical assessment (remission, response and non
response) was based on Present's criteria. Rectoscopic patterns, MRI Van Assche
score, and MRI fistula activity signs (T2 signal and contrast enhancement) were
collected for the two MR examinations. Fistula healing was defined as the absence
of T2 hyperintensity and contrast enhancement on MRI. Deep remission was defined
as the association of both clinical remission, absence of anal canal ulcers and
healing on MRI. Characteristics and imaging patterns of patients with and without
deep remission were compared by univariate and multivariate analyses. RESULTS:
Forty-nine consecutive patients (31 females and 18 males) were included. They
ranged in age from 14-70 years (mean, 33 years). MRI and clinical assessment were
performed after a mean period of exposure to anti-TNF-alpha therapy of 40 +/- 3.7
mo. Clinical remission, response and non-response were observed in 53.1%, 20.4%,
and 26.5% of patients, respectively. Deep remission was observed in 32.7% of
patients. Among the 26 patients in clinical remission, 10 had persisting
inflammation of fistulas on MRI (T2 hyperintensity, n = 7; contrast enhancement,
n = 10). Univariate analysis showed that deep remission was associated with the
absence of rectal involvement and the absence of switch of anti-TNF-alpha
treatment or surgery requirement. Multivariate analysis demonstrated that only
the absence of rectal involvement (OR = 4.6; 95%CI: 1.03-20.5) was associated
with deep remission. CONCLUSION: Deep remission is achieved in approximately one
third of patients on maintenance anti-TNF-alpha therapy. Absence of rectal
involvement is predictive of deep remission.
PMID- 28694670
TI - New totally intracorporeal reconstructive approach after robotic total
gastrectomy: Technical details and short-term outcomes.
AB - AIM: To show outcomes of our series of patients that underwent a total
gastrectomy with a robotic approach and highlight the technical details of a
proposed solution for the reconstruction phase. METHODS: Data of gastrectomies
performed from May 2014 to October 2016, were extracted and analyzed. Basic
characteristics of patients, surgical and clinical outcomes were reported. The
technique for reconstruction (Parisi Technique) consists on a loop of bowel
shifted up antecolic to directly perform the esophago-enteric anastomosis
followed by a second loop, measured up to 40 cm starting from the esojejunostomy,
fixed to the biliary limb to create an enteroenteric anastomosis. The continuity
between the two anastomoses is interrupted just firing a linear stapler, so
obtaining the Roux-en-Y by avoiding to interrupt the mesentery. RESULTS: Fifty
five patients were considered in the present analysis. Estimated blood loss was
126.55 +/- 73 mL, no conversions to open surgery occurred, R0 resections were
obtained in all cases. Hospital stay was 5 (3-17) d, no anastomotic leakage
occurred. Overall, a fast functional recovery was shown with a median of 3 (3-6)
d in starting a solid diet. CONCLUSION: Robotic surgery and the adoption of a
tailored reconstruction technique have increased the feasibility and safety of a
minimally invasive approach for total gastrectomy. The present series of patients
shows its implementation in a western center with satisfying short-term outcomes.
PMID- 28694671
TI - Substantial hepatic necrosis is prognostic in fulminant liver failure.
AB - AIM: To evaluate if any association existed between the extent of hepatic
necrosis in initial liver biopsies and patient survival. METHODS: Thirty-seven
patients with fulminant liver failure, whose liver biopsy exhibited substantial
necrosis, were identified and included in the study. The histological and
clinical data was then analyzed in order to assess the relationship between the
extent of necrosis and patient survival, with and without liver transplantation.
The patients were grouped based on the etiology of hepatic necrosis. Each of the
etiology groups were then further stratified according to whether or not they had
received a liver transplant post-index biopsy, and whether or not the patient
survived. RESULTS: The core tissue length ranged from 5 to 44 mm with an average
of 23 mm. Causes of necrosis included 14 autoimmune hepatitis, 10 drug induced
liver injury (DILI), 9 hepatitis virus infection, and 4 unknown origin. Among
them, 11 showed submassive (26%-75% of the parenchymal volume) and 26 massive
(76%-100%) necrosis. Transplant-free survival was worse in patients with a higher
extent of necrosis (40%, 71.4% and 100% in groups with necrosis of 76%-100%, 51%
75% and 26%-50%, respectively). Additionally, transplant-free survival rates were
66.7%, 57.1%, and 25.0% in groups of autoimmune hepatitis, DILI, and viral
hepatitis, respectively. Even after liver transplantation, the survival rate in
patients as a result of viral hepatitis remained the lowest (80%, 100%, and 40%
in groups of autoimmune hepatitis, DILI, and viral hepatitis, respectively).
CONCLUSION: Adequate liver biopsy with more than 75% necrosis is associated with
significant transplant-free mortality that is critical in predicting survival.
PMID- 28694672
TI - Benefit of everolimus in treatment of an intrahepatic cholangiocarcinoma patient
with a PIK3CA mutation.
AB - Intrahepatic cholangiocarcinoma (ICC) is a relatively rare form of liver cancer
with a poor prognosis. The therapeutic options for patients with advanced ICC are
limited and usually ineffective. There is currently no approved targeted therapy
for ICC, although accumulating evidence supports inhibition of the PI3K/Akt/mTOR
signaling pathway as a promising therapeutic strategy in the treatment of ICC.
Here, we report a patient with stage IV ICC harboring a PIK3CA mutation who
responded well to the mTOR inhibitor everolimus. Computed tomography and magnetic
resonance imaging demonstrated shrinkage of the tumor and maintenance of a
partial response for 6.5 mo after everolimus treatment as the best response. To
the best of our knowledge, this is the first clinical case report in the
literature of clinical benefit from everolimus treatment in an ICC patient with
PIK3CA mutation.
PMID- 28694673
TI - Manual physical therapy for chronic pain: the complex whole is greater than the
sum of its parts.
PMID- 28694674
TI - Mechanisms of chronic pain - key considerations for appropriate physical therapy
management.
AB - In last decades, knowledge of nociceptive pain mechanisms has expanded rapidly.
The use of quantitative sensory testing has provided evidence that peripheral and
central sensitization mechanisms play a relevant role in localized and widespread
chronic pain syndromes. In fact, almost any patient suffering with a chronic pain
condition will demonstrate impairments in the central nervous system. In
addition, it is accepted that pain is associated with different types of trigger
factors including social, physiological, and psychological. This rational has
provoked a change in the understanding of potential mechanisms of manual
therapies, changing from a biomechanical/medical viewpoint, to a
neurophysiological/nociceptive viewpoint. Therefore, interventions for patients
with chronic pain should be applied based on current knowledge of nociceptive
mechanisms since determining potential drivers of the sensitization process is
critical for effective management. The current paper reviews mechanisms of
chronic pain from a clinical and neurophysiological point of view and summarizes
key messages for clinicians for proper management of individuals with chronic
pain.
PMID- 28694675
TI - Changes in psychosocial well-being after mindfulness-based stress reduction: a
prospective cohort study.
AB - Objectives: The primary purpose of the current study was to assess the effects of
a mindfulness-based stress reduction (MBSR) program, facilitated by non
psychologist clinicians, for improving psychosocial well-being. A secondary
purpose of the current study was to explore the role of self-compassion as a
potential underlying factor for improvements in emotional distress. Application
of these findings to a physical therapy setting is provided. Methods: One hundred
and thirty participants with a variety of medical complaints completed an eight
week MBSR program at Vanderbilt University's Osher Center for Integrative
Medicine. Prior to the intervention and at the eight-week time point,
participants completed measures for emotional distress (Brief Symptom Inventory),
stress (Perceived Stress Scale-10), mindfulness (Mindfulness Attention and
Awareness Scale), and self-compassion (Self-Compassion Scale). Wilcoxon signed
rank test was used to evaluate changes in outcomes after MBSR. Linear model
estimation using ordinary least squares was used to evaluate the association
between changes in self-compassion with changes in emotional distress. Results:
Following MBSR, participants reported significant reductions in emotional
distress (p < 0.001). Additionally, participants reported improvements in
mindfulness and self-compassion (p < 0.001). Linear regression model revealed
that changes in self-compassion were significantly associated with changes in
emotional distress (p < 0.001). Discussion: An MBSR program conducted by non
psychologist clinicians was associated with improvements in emotional distress,
stress, and self-compassion. MBSR is a promising adjunct intervention in which
principles can be integrated within a physical therapy approach for chronic
conditions. Level of Evidence: 3B.
PMID- 28694676
TI - 3D augmented reality mirror visual feedback therapy applied to the treatment of
persistent, unilateral upper extremity neuropathic pain: a preliminary study.
AB - Objective: We assessed whether or not pain relief could be achieved with a new
system that combines 3D augmented reality system (3DARS) and the principles of
mirror visual feedback. Methods: Twenty-two patients between 18 and 75 years of
age who suffered of chronic neuropathic pain. Each patient performed five 3DARS
sessions treatment of 20 mins spread over a period of one week. The following
pain parameters were assessed: (1) visual analogic scale after each treatment
session (2) McGill pain scale and DN4 questionnaire were completed before the
first session and 24 h after the last session. Results: The mean improvement of
VAS per session was 29% (p < 0.001). There was an immediate session effect
demonstrating a systematic improvement in pain between the beginning and the end
of each session. We noted that this pain reduction was partially preserved until
the next session. If we compare the pain level at baseline and 24 h after the
last session, there was a significant decrease (p < 0.001) of pain of 37%. There
was a significant decrease (p < 0.001) on the McGill Pain Questionnaire and DN4
questionnaire (p < 0.01). Conclusion: Our results indicate that 3DARS induced a
significant pain decrease for patients who presented chronic neuropathic pain in
a unilateral upper extremity. While further research is necessary before
definitive conclusions can be drawn, clinicians could implement the approach as a
preparatory adjunct for providing temporary pain relief aimed at enhancing
chronic pain patients' tolerance of manual therapy and exercise intervention.
Level of Evidence: 4.
PMID- 28694677
TI - Does shared decision making results in better health related outcomes for
individuals with painful musculoskeletal disorders? A systematic review.
AB - Background: Shared Decision-Making (SDM) is a dynamic process by which the health
care professional and the patient influence each other in making health-related
choices or decisions. SDM is strongly embedded in today's health care approaches,
and is advocated as an ideal model since it renders individuals more control
towards the health care they choose to receive, and has been shown to improve
patient outcomes. Objectives: The goal of this systematic review was to
investigate the added-value of SDM on clinical health-related outcomes in
patients with a variety of musculoskeletal conditions. Data sources: PubMed and
CINAHL. Study selection: PRISMA guidelines were followed for this review. To be
considered for review, the study had to meet all the following criteria: (1)
prospective studies that involved treatment decision-making; (2) randomized
controlled trial design; (3) involving patients faced with having to make a
treatment decision; (4) comparing SDM with a control intervention and (5)
including one or more of the following outcome measures: well-being, costs,
health-related pain or disability measures, or quality of life. Study appraisal:
A priori, we determined to perform methodological quality assessment using the
Cochrane Risk of Bias tool for randomized controlled trials. Results: We did not
find a single study that looked at the true effect of SDM on patient reported
outcomes in a population with musculoskeletal pain. Conclusion: For the
management of painful musculoskeletal conditions, in the light of the current
evidence (none), we estimate that it would be wise to explore the effectiveness
of SDM before forcing its large-scale implementation in rehabilitation.
PMID- 28694678
TI - Placebo disclosure does not result in negative changes in mood or attitudes
towards health care or the provider.
AB - Objectives: The purposes of this study were to (1) determine whether disclosure
of having received a placebo treatment following participation in a randomized
manual therapy trial resulted in changes in negative mood or attitudes towards
health care and the provider and (2) examine the association between changes in
mood or attitude and changes in clinical outcomes over the two-week study period.
Methods: Participants with low back pain (N = 110) were randomly assigned to
receive a spinal manipulative therapy (SMT), a standard placebo SMT in which
participants were aware of a chance of receiving a placebo, an enhanced placebo
SMT in which participants were instructed 'the manual therapy technique you will
receive has been shown to significantly reduce low back pain in some people,' or
no treatment. Outcomes included pain (Numeric Rating Scale), disability (Oswestry
Disability Index), and negative mood and attitudes towards health care and the
provider (visual analog scales). Pain and disability were obtained at baseline
and two weeks. Mood and attitude measures were assessed at baseline, at the start
of the final session, and upon completion of the final session following
disclosure of group assignment. Results: Disclosure of having received a placebo
treatment was not associated with worsening of mood or attitudes towards health
care or the provider (p > 0.05). A small, but significant (p < 0.05) association
was observed between two-week changes in disability and immediate changes in mood
(r = 0.31-0.36) upon disclosure of having received a placebo. This analysis
indicates an association between larger improvements in disability and more
positive changes in mood. Discussion: Placebo treatment use in clinical practice
is common yet controversial due to the deceptive nature. Our findings suggest
disclosure of having received a placebo treatment is not associated with adverse
changes in negative mood or attitudes towards health care or the provider.
PMID- 28694679
TI - A clinical perspective on a pain neuroscience education approach to manual
therapy.
AB - In recent years, there has been an increased interest in pain neuroscience
education (PNE) in physical therapy. There is growing evidence for the efficacy
of PNE to decrease pain, disability, fear-avoidance, pain catastrophization,
limited movement, and health care utilization in people struggling with pain. PNE
teaches people in pain more about the biology and physiology of their pain
experience including processes such as central sensitization, peripheral
sensitization, allodynia, inhibition, facilitation, neuroplasticity and more.
PNE's neurobiological model often finds itself at odds with traditional
biomedical models used in physical therapy. Traditional biomedical models,
focusing on anatomy, pathoanatomy, and biomechanics have been shown to have
limited efficacy in helping people understand their pain, especially chronic
pain, and may in fact even increase a person's pain experience by increasing fear
avoidance and pain catastrophization. An area of physical therapy where the
biomedical model is used a lot is manual therapy. This contrast between PNE and
manual therapy has seemingly polarized followers from each approach to see PNE as
a 'hands-off' approach even having clinicians categorize patients as either in
need of receiving PNE (with no hands-on), or hands-on with no PNE. In this paper,
we explore the notion of PNE and manual therapy co-existing. PNE research has
shown to have immediate effects of various clinical signs and symptoms associated
with central sensitization. Using a model of sensitization (innocuous, noxious,
and allodynia), we argue that PNE can be used in a manual therapy model,
especially treating someone where the nervous system has become increasingly
hypervigilant. Level of Evidence: VII.
PMID- 28694680
TI - Developing a Tailored Texting Preventive Intervention: A Card Sort Methodology.
AB - PURPOSE: Intervention content written by adults for youth can result in
miscommunication due to generational and cultural differences. Inviting at-risk
youth to participate in the creation of intervention material can augment
acceptability for their peers. METHODS: To improve intervention messaging, the
present study examines the utility of a card sort technique when creating
cellular phone text messages to be used in a preventive substance use
intervention. During focus groups with 24 youth who are exiting the foster care
system - a population with distinct cultural attributes - participants were asked
to rate stage of change-specific health messages rooted in Motivational
Interviewing and the Transtheoretical Model. RESULTS: Participants unanimously
favored content that encouraged autonomy and choice. Statements that invited a
"look to the future" were also rated favorably. Messages that referenced the past
were not rated well, as were suggestions for professional assistance. Finally,
encouragement to receive social support for change was met with ambivalence.
While some participants regarded support as helpful, many others felt a severe
lack of support in their lives, possibly prompting further substance use.
CONCLUSIONS: Youth exiting foster care constitute a unique population whose voice
is paramount in the development of interventions. The content present in
traditional approaches to substance use prevention (e.g., increasing social
support) may not apply to this group of vulnerable youth. The card sort technique
has strong potential to evoke youth-specific intervention content that is more
readily understood and accepted by target audiences.
PMID- 28694681
TI - Patients' Knowledge and Perceptions of Morcellation.
AB - BACKGROUND AND OBJECTIVES: Morcellation has received increased media and
professional attention, but it remains unclear how much the average patient knows
about this topic. We sought to evaluate patients' knowledge of morcellation,
assess their perceptions of the risks and benefits, and determine how these
perceptions affect their decision regarding the route of surgery. METHODS:
Anonymous paper surveys were administered to 500 patients attending gynecologic
appointments at the University of Michigan. Survey questions gathered demographic
information and assessed knowledge of various surgical approaches for
hysterectomy and myomectomy. Questions regarding patients' knowledge of
morcellation explored various types of morcellation and the risks and benefits of
this procedure. RESULTS: Of the 500 surveys administered, 396 patients answered
at least 1 survey question resulting in a response rate of 79.2%. The mean +/- SD
age of respondents was 47.0 +/- 14.1 years, 80.8% were white, and 83.1% had
completed some college. Only 8.3% of patients reported that they had ever heard
of morcellation. Even among women who were actively considering a hysterectomy or
myomectomy (n = 33) or those who had undergone a hysterectomy or myomectomy (n =
98), only 12.1 and 7.1%, respectively, had heard of morcellation. Of those who
had heard of morcellation (n = 32), only 9.4% correctly identified the definition
in a multiple-choice question. Only 4.0% of women would choose an abdominal
approach to avoid morcellation. CONCLUSIONS: Patients have very little knowledge
about morcellation and most patients have never heard of the procedure. Very few
patients would refuse morcellation and opt for an abdominal surgery instead.
PMID- 28694682
TI - Laparoscopic Suturing as a Barrier to Broader Adoption of Laparoscopic Surgery.
AB - BACKGROUND: Laparoscopic surgery is increasingly replacing the open procedure
because of its many patient-related benefits that are well aligned with policies
and programs that seek to optimize health system performance. However, widespread
adoption of laparoscopic surgery has been slow, in part, because of the
complexity of laparoscopic suturing. The objective of this study was to review
the clinical and economic impacts of laparoscopic suturing in key procedures and
to assess its role as a barrier to the broader adoption of laparoscopic surgery.
DATABASE: A medical literature search of MEDLINE, EMBASE, and BIOSIS from January
2010 through June 2016 identified 47 relevant articles. CONCLUSION: Laparoscopic
suturing and intracorporeal knot tying may result in extended surgical time,
complications, and surgeon errors, while improving patient quality of life
through improved cosmesis, diet toleration, and better bowel movements. Despite
advancement in surgical techniques and the availability of newer surgical tools,
the complexity of laparoscopic suturing continues to be a barrier to greater
adoption of MIS. The results of the study underscore the need for development of
proficiency in laparoscopic suturing, which may help improve patient outcomes and
reduce healthcare costs.
PMID- 28694684
TI - Comparison of Joint Loading in Badminton Lunging between Professional and Amateur
Badminton Players.
AB - The knee and ankle are the two most injured joints associated with the sport of
badminton. This study evaluates biomechanical factors between professional and
amateur badminton players using an injury mechanism model. The aim of this study
was to investigate the kinematic motion and kinetic loading differences of the
right knee and ankle while performing a maximal right lunge. Amateur players
exhibited greater ankle range of motion (p < 0.05, r = 0.89) and inversion joint
moment (p < 0.05, r = 0.54) in the frontal plane as well as greater internal
joint rotation moment (p < 0.05, r = 0.28) in the horizontal plane. In contrast,
professional badminton players presented a greater knee joint moment in the
sagittal (p < 0.05, r = 0.59) and frontal (p < 0.05, r = 0.37) planes, which may
be associated with increased knee ligamentous injury risk. To avoid injury, the
players need to forcefully extend the knee with internal rotation, strengthen the
muscles around the ankle ligament, and maximise joint coordination during
training. The injuries recorded and the forces responsible for the injuries seem
to have developed during training activity. Training programmes and injury
prevention strategies for badminton players should account for these findings to
reduce potential injury to the ankle and knee.
PMID- 28694685
TI - Differential effect of platelet-rich plasma fractions on beta1-integrin
signaling, collagen biosynthesis, and prolidase activity in human skin
fibroblasts.
AB - The study was conducted to evaluate the effects of platelet-rich plasma (PRP),
supernatant of PRP (SPRP) obtained by centrifugation, and supernatant of
activated PRP (SActi-PRP) obtained by Ca2+ solution-treated PRP on collagen
biosynthesis, prolidase activity, and beta1-integrin signaling in cultured human
skin fibroblasts. Incubation of fibroblasts with 5% PRP for 24 h contributed to
~5-fold increase in collagen biosynthesis compared to the control. In the cells
treated with 5% of SPRP or SActi-PRP, collagen biosynthesis showed a 3-fold
increase of the control. PRP, SPRP, and SActi-PRP stimulated prolidase activity
similar to collagen biosynthesis. Collagen biosynthesis and prolidase activity
are regulated by beta1-integrin receptor signaling. Incubation of fibroblasts
with PRP for 24 h contributed to a dose-dependent increase in the expression of
beta1-integrin receptor, while SActi-PRP increased the process to a much lower
extent. SPRP had no effect on the beta1-integrin receptor expression. All the
studied fractions of blood increased the expression of FAK as well as the
expression of phosphorylated MAP-kinases. However, PRP was found to be the most
effective stimulator of expression of these particular kinases. These studies
suggest that a complex of factors, including growth factors, adhesion molecules,
and prolidase contained in PRP, all evoke growth and collagen-promoting
activities in human dermal fibroblasts.
PMID- 28694686
TI - Molecular docking, QSAR and ADMET studies of withanolide analogs against breast
cancer.
AB - Withanolides are a group of pharmacologically active compounds present in most
prodigal amounts in roots and leaves of Withania somnifera (Indian ginseng), one
of the most important medicinal plants of Indian traditional practice of
medicine. Withanolides are steroidal lactones (highly oxygenated C-28
phytochemicals) and have been reported to exhibit immunomodulatory, anticancer
and other activities. In the present study, a quantitative structure activity
relationship (QSAR) model was developed by a forward stepwise multiple linear
regression method to predict the activity of withanolide analogs against human
breast cancer. The most effective QSAR model for anticancer activity against the
SK-Br-3 cell showed the best correlation with activity (r2=0.93 and rCV2 =0.90).
Similarly, cross-validation regression coefficient (rCV2=0.85) of the best QSAR
model against the MCF7/BUS cells showed a high correlation (r2=0.91). In
particular, compounds CID_73621, CID_435144, CID_301751 and CID_3372729 have a
marked antiproliferative activity against the MCF7/BUS cells, while 2,3
dihydrowithaferin A-3-beta-O-sulfate, withanolide 5, withanolide A, withaferin A,
CID_10413139, CID_11294368, CID_53477765, CID_135887, CID_301751 and CID_3372729
have a high activity against the Sk-Br-3 cells compared to standard drugs 5
fluorouracil (5-FU) and camptothecin. Molecular docking was performed to study
the binding conformations and different bonding behaviors, in order to reveal the
plausible mechanism of action behind higher accumulation of active withanolide
analogs with beta-tubulin. The results of the present study may help in the
designing of lead compound with improved activity.
PMID- 28694687
TI - Efficacy and safety of retinol palmitate ophthalmic solution in the treatment of
dry eye: a Japanese Phase II clinical trial.
AB - PURPOSE: The purpose of this study was to investigate the efficacy and safety of
the administration of retinol palmitate (VApal) ophthalmic solution (500 IU/mL)
for the treatment of patients with dry eye. PATIENTS AND METHODS: This study
included 66 patients with dry eye. After a 2-week washout period, patients were
randomized (1:1) into either a VApal ophthalmic solution or a placebo group, and
a single drop of either solution was administered six times daily for 4 weeks.
Efficacy measures were 12 subjective symptoms, rose bengal (RB) and fluorescein
staining scores, tear film breakup time, and tear secretion. Safety measures
included clinical blood and urine analyses and adverse event recordings. RESULTS:
In comparisons of the two groups, the mean change in RB staining score from
baseline was significantly lower in the VApal group at 2 and 4 weeks (P<0.05 and
P<0.01, respectively). Furthermore, the fluorescein clearance rate (fluorescein
staining score) was significantly higher in the VApal group at 4 weeks (P<0.05).
The VApal group showed a significant improvement in blurred vision at 1 and 2
weeks (P<0.01 and P<0.05, respectively), and the mean change in the total score
for subjective symptoms from baseline was significantly lower in the VApal group
at 1 week (P<0.05). In before- and after-intervention comparisons, the
fluorescein and RB staining scores showed improvement in both groups. Improvement
was noted for 11 subjective symptoms in the VApal group and for seven symptoms in
the placebo group. No significant differences in adverse events and reactions
were found between the groups. CONCLUSION: VApal ophthalmic solution (500 IU/mL)
is safe and effective for the treatment of patients with dry eye.
PMID- 28694688
TI - Total flavonoids from Rhizoma Drynariae (Gusuibu) for treating osteoporotic
fractures: implication in clinical practice.
AB - This systematic review was performed to determine the clinical efficacy and
safety of total flavonoids from Rhizoma Drynariae (TFRD) for osteoporotic
fractures and to provide clear evidence for clinical practice. Eight databases
were searched to identify relevant randomized controlled trials (RCTs) until
December 2016. Six RCTs involving 846 patients were included. The primary
outcomes included fracture recurrence and death. Meta-analysis showed that both
the combination therapy and TFRD alone were better than conventional treatments
in improving bone mineral density (BMD) value (weighted mean difference [WMD]
=3.68, 95% confidence interval [CI]: 0.01 to 0.04, P=0.0002), (WMD =0.14; 95% CI:
0.11 to 0.16; P<0.00001), respectively, and enhancing therapeutic effect (OR
=0.25; 95% CI: 0.12 to 0.51; P=0.0002). Thirty-three patients experienced adverse
drug reactions (ADRs), none of the ADRs were severe and all were resolved after
symptomatic treatments. Gastrointestinal symptoms were the most common ADRs in
the usage of TFRD. Overall, the effect of TFRD on osteoporotic fractures was
supported by improving BMD and therapeutic effect. Due to the methodological
drawbacks of the included studies, the conclusions should be treated with caution
for future research. Registration number: CRD42017052797.
PMID- 28694689
TI - Synthesis and cytotoxic activities of novel 4-methoxy-substituted and 5-methyl
substituted (3'S,4'S)-(-)-cis-khellactone derivatives that induce apoptosis via
the intrinsic pathway.
AB - This study deals with the design and synthesis of a series of novel 4-methoxy
substituted and 5-methyl-substituted (3'S,4'S)-(-)-cis-khellactones. The newly
synthesized compounds were characterized by 1H nuclear magnetic resonance (NMR),
13C-NMR, mass spectrometry, and elemental analysis. All the derivatives were
subjected to in vitro cytotoxicity screening against HEPG-2 (human liver
carcinoma), SGC-7901 (human gastric carcinoma), and LS174T (human colon
carcinoma), by using the MTT assay. The results revealed that several of the 4
methoxy-substituted compounds exhibited potent cytotoxicity. Among these,
compound 12e showed the highest activity against cancer cells which 50%
inhibitory concentration (IC50) values were in the range of 6.1-9.2 MUM with low
toxicity on normal human hepatocyte. Preliminary investigation of possible
mechanisms of action of compound 12e against HEPG-2 cells indicated possible
induction of apoptosis, as determined by morphological observations and Annexin
V/propidium iodide (PI) double staining, in addition to apparent dissipation of
mitochondrial membrane potential (MMP), as measured by 5,5',6,6'-tetrachloro
1,1',3,3'-tetraethyl-imidacarbocyanine iodide (JC-1) staining in combination with
the activation of caspase-9 and caspase-3 by Western blot analysis. Overall, the
data suggest that compound 12e may be a promising potential anti-cancer agent
that could act primarily by inducing apoptosis through the mitochondria-mediated
intrinsic pathway in human hepatoma cells.
PMID- 28694690
TI - Social participation and perceived depression among elderly population in South
Africa.
AB - There is a growing consensus regarding the influence of various psychosocial
factors such as degree of social participation on health and disease outcomes,
quality of life, and general well-being. Older individuals with diminished motor
and physical functionality suffer a heightened risk of social exclusion and
loneliness. Previous studies have demonstrated the association between social
exclusion and loneliness with mental health among the older population. In the
present study, we aimed to investigate whether or not difficulty in social
participation has any relationship with perceived depression among older
individuals in South Africa. We collected cross-sectional data from the SAGE Well
Being of Older People Study 2010 on 422 men and women aged 50 years and above.
Perceived depression and loss of interest in things (eg, personal relationships,
hobbies) during the last 12 months were used as outcome variables with difficulty
in joining community activities, relationships/community participation,
friendships, and visiting family/friends as the main explanatory variables.
Findings indicated that the prevalence of self-reported depression and the
feeling of reduced interest in most things were respectively 51.9% and 43.8%. In
the multivariate analysis, those who reported difficulty in joining community
activities had respectively 64% (OR =1.639; 95% CI =1.081-2.583) and 69% (OR
=1.685; 95% CI) higher odds of depression and loss of interest in things compared
with those who did not report any difficulty. The study concludes that addressing
the barriers to engaging in community activities may help minimize burden of
depression among the elderly population in South Africa. Furthermore, large-scale
studies are warranted to explore the social and structural barriers which
constrain community participation among the elderly population.
PMID- 28694691
TI - Assessment of renal function in geriatric palliative care patients - comparison
of creatinine-based estimation equations.
AB - BACKGROUND: Renal function impairment is common in geriatric palliative care
patients. Accurate assessment of renal function is necessary for appropriate drug
dosage. Several equations are used to estimate kidney function. AIMS: 1) To
investigate the differences (Delta) in kidney function assessed with simplified
Modifi-cation of Diet in Renal Disease (MDRD), Berlin Initiative Study (BIS1),
and Cockcroft-Gault (C-G) formulas in geriatric palliative care patients, and 2)
to assess factors that may influence these differences. METHODS: A retrospective
analysis of data of patients aged >=70 years admitted to a palliative care in
patient unit. The agreement between C-G, MDRD, and BIS1 equations was assessed
with Bland-Altman analysis. Partial correlation analysis was used to analyze
factors influencing the discordance. RESULTS: A total of 174 patients (67 men;
mean age 77.9+/-5.8 years) were enrolled. The mean Delta MDRD and C-G was 18.6
(95% limits of agreement 55.3 and -18.2). The mean Delta BIS1 and C-G was 6.1
(25.7 and -13.5), and the mean Delta MDRD and BIS1 was 12.5 (40.6 and -15.6).
According to the National Kidney Foundation classification, 61 (35.1%) patients
were differently staged using MDRD and C-G, while20% of patients were differently
staged with BIS1 and C-G and MDRD and BIS1. Serum creatinine (SCr) and body mass
index (BMI) had the most important influence on variability of Delta MDRD and C-G
(partial R2 37.7% and 28.4%). Variability of Delta BIS1 and C-G was mostly
influenced by BMI (34.8%) and variability of Delta MDRD and BIS1 by SCr (42.2%).
Age had relatively low influence on differences between equations (3.1%-9.5%).
CONCLUSION: There is a considerable disagreement between renal function
estimation formulas, especially MDRD and C-G in geriatric palliative care
patients, which may lead to errors in drug dosage adjustment. The magnitude of
discrepancy increases with lower SCr, lower BMI, and higher age.
PMID- 28694692
TI - Health resource utilization for inpatients with COPD treated with nebulized
arformoterol or nebulized formoterol.
AB - OBJECTIVE: Arformoterol is the (R,R)-enantiomer of formoterol. Preclinical
studies suggest that it is a stronger bronchodilator than the racemic (R,R/S,S)
formoterol; however, its potential clinical advantages have not been
demonstrated. This study compared the length of stay (LOS), 30-day readmission
rates, and doses of rescue medication administered in hospitalized patients with
COPD who were treated with nebulized arformoterol or nebulized formoterol.
METHODS: This retrospective analysis utilized data from Premier, Inc. (Charlotte,
NC, USA), the largest nationwide hospital-based administrative database. COPD
patients >=40 years of age were included if they were hospitalized between
January 2011 and July 2014, had no asthma diagnoses, and were treated with
nebulized arformoterol or nebulized formoterol. LOS was measured from the day the
patients initiated the study medication (index day). Rescue medications were
defined as short-acting bronchodilators used from the index day onward.
Multivariate statistical models included a random effect for hospital and
controlled for patient demographics, hospital characteristics, admission
characteristics, prior hospitalizations, comorbidities, pre-index service use,
and pre-index medication use. RESULTS: A total of 7,876 patients received
arformoterol, and 3,612 patients received nebulized formoterol. There was no
significant difference in 30-day all-cause (arformoterol =11.9%, formoterol
=12.1%, odds ratio [OR] =0.981, P=0.82) or COPD-related hospital readmission
rates (arformoterol =8.0%, formoterol =8.0%, OR =1.002, P=0.98) after adjusting
for covariates. The adjusted mean LOS was significantly shorter for arformoterol
treated vs formoterol-treated patients (4.6 vs 4.9 days, P=0.039), and
arformoterol-treated patients used significantly fewer doses of rescue
medications vs formoterol-treated patients (5.9 vs 6.6 doses, P=0.006).
CONCLUSION: During inpatient stays, treating with arformoterol instead of
nebulized formoterol may lead to shorter LOS and lower rescue medication use.
PMID- 28694693
TI - Prevalence and characteristics of asthma-COPD overlap syndrome identified by a
stepwise approach.
AB - BACKGROUND AND OBJECTIVE: There is increasing recognition of asthma-COPD overlap
syndrome (ACOS), which shares some features of both asthma and COPD; however, the
prevalence and characteristics of ACOS are not well understood. The aim of this
study was to investigate the prevalence of ACOS among patients with COPD and its
characteristics using a stepwise approach as stated in the recent report of the
Global Initiative for Asthma (GINA) and the Global Initiative for Chronic
Obstructive Lung Disease (GOLD). METHODS: This multicenter, cross-sectional,
observational study enrolled outpatients who were receiving medical treatment for
COPD. Clinical data, including spirometry results, were retrieved from medical
records. For symptom assessment, patients were asked to complete the Clinical
COPD questionnaire and the modified British Medical Research Council
questionnaire. RESULTS: Of the 1,008 patients analyzed, 167 (16.6%) had syndromic
features of ACOS. Of the total number of patients, 93 and 42 (9.2% and 4.2%) also
had a predefined clinical variability of >=12%/>=200 mL and >=12%/>=400 mL in
forced expiratory volume in 1 second (FEV1), respectively, and therefore were
identified as having ACOS. Conversely, the number of patients who had either
syndromic or spirometric feature of ACOS was 595 (59.0%, >=12%/>=200 mL FEV1
clinical variability), and 328 patients (32.5%, >=12%/>=400 mL FEV1 clinical
variability) had both the features. Patients identified as having ACOS were of
significantly younger age, had a shorter duration of COPD, lower number of pack
years, better lung function, milder dyspnea symptoms, and higher peripheral blood
eosinophil values compared with patients with COPD alone. The rate of
exacerbations in the previous year was not significantly different between the
ACOS and COPD groups. CONCLUSION: Using a stepwise approach, as stated in the
GINA/GOLD report, the proportions of patients identified as having ACOS were
found to be 9.2% and 4.2% (depending on the FEV1 variability cutoff used) among
the 1,008 outpatients medically treated for COPD in a real-life clinical setting.
PMID- 28694694
TI - Expression profiling of miRNA-145 and miRNA-338 in serum and sputum of patients
with COPD, asthma, and asthma-COPD overlap syndrome phenotype.
AB - BACKGROUND AND OBJECTIVES: A new phenotype with overlapping characteristics
between asthma and chronic obstructive pulmonary disease (COPD) called asthma
COPD overlap syndrome (ACOS) is emerging among inflammation diseases. To date,
there is no agreement on specific criteria to define this syndrome, and the
current guidelines are insufficient to classify the analogy and differences
between overlap and COPD or asthma phenotypes. It would be necessary to identify
new biomarkers able to identify these diseases clearly. Thus, the aim of this
study was to identify a serum and supernatant of sputum microRNA (miRNA)
expression profile of miRNA-145 and miRNA-338 in patients with asthma (n=13),
COPD (n=31), and ACOS (n=8) and controls (n=7). METHODS: The expression was
evaluated using quantitative real-time polymerase chain reaction (qRT-PCR). For
statistical analysis, the ANOVA test, Kruskal-Wallis test, Mann-Whitney U-test,
and Spearman's rank correlation were used. RESULTS: The main finding of this work
is that the expression of miRNA-338 is higher in the supernatant of different
obstructive diseases than in peripheral blood, while miRNA-145 is higher only in
the supernatant of asthma patients. The expression of both selected miRNAs is
higher in the supernatant of asthma and COPD patients than in controls.
CONCLUSION: Differences in sputum miRNA expression profile were observed between
patients with ACOS and asthma or COPD, which underline the potential role of
miRNA as a biomarker that is able to discriminate patients with ACOS, asthma, and
COPD.
PMID- 28694695
TI - Relationship between blood eosinophils, clinical characteristics, and mortality
in patients with COPD.
AB - In patients with COPD, there is controversy regarding the association of blood
eosinophil (Eos) levels with 1) exacerbation frequency and 2) the effect of
inhaled corticosteroids for prevention of exacerbations. To determine whether Eos
define subgroups of patients exhibiting attributes of COPD clinical phenotypes,
we compared clinical features and mortality rates in COPD patients from the
Initiatives BPCO French cohort categorized using different thresholds of blood
Eos levels. The following data were collected at inclusion: medical and smoking
history, occupational exposures, dyspnea, cough and sputum production,
exacerbations in the previous year, history of allergy and asthma, nasal
symptoms, body mass index, St George Respiratory Questionnaire (SGRQ) total
score, post-bronchodilator spirometry, comorbidities, and medications. Three-year
survival between groups was compared using Kaplan-Meier analysis. Three sets of
analyses were performed to compare patients with >=2% versus <2%, >=3% versus
<3%, and >=4% versus <4% Eos. Eos was available in 458 patients (mean age: 62
years, 72% male, mean forced expiratory volume in 1 second: 51% pred), including
235 patients with Eos >=2% (49%), 149 with Eos >=3% (33%), and 90 with Eos >=4%
(20%). For all cutoffs, there was no difference between Eos+ and Eos- groups in
univariate analyses except for diabetes and SGRQ score (more frequent and more
impaired, respectively, in lower Eos categories). In particular, there was no
difference in exacerbation rate, history of asthma, or three-year survival. In
conclusion, regardless of the cutoff, Eos+ COPD patients exhibited no specific
characteristic in terms of symptoms, lung function, exacerbation rate, and
prognosis. These findings suggest that the association of higher Eos with
exacerbations reported in previous studies could be population specific, which
does not support generalizing the use of Eos as a biomarker for COPD phenotyping.
PMID- 28694696
TI - Th17 profile in COPD exacerbations.
AB - COPD is characterized by an ongoing inflammatory process of the airways that
leads to obstruction or limitation of airflow. It is mainly associated with
exposure to cigarette smoke. In addition, it is considered, at present, a serious
public health problem, ranking fourth in mortality worldwide. Many cells
participate in the pathophysiology of COPD, the most important are neutrophils,
macrophages and CD4+ and CD8+ T cells. Neutrophil migration to the inflammation
area could be mediated largely by cytokines related to CD4+ Th17 lymphocytes,
because it has been shown that IL-17A, IL-17F and IL-22 act as inducers for
CXCL8, CXCL1, CXCL5, G-CSF, and GM-CSF secretion by epithelial cells of the
airways. The aims of these molecules are differentiation, proliferation and
recruitment of neutrophils. Furthermore, it is believed that CD4+ lymphocytes
Th17 may be involved in protection against pathogens for which Th1 and Th2 are
not prepared to fight. In COPD exacerbations, there is an increased cellularity
in the lung region and respiratory tract. Therefore, the increase in the number
of neutrophils and macrophages in the airways and the increase in proinflammatory
cytokines are directly related to the severity of exacerbations and that is the
importance of the functions of Th17 profile in this entity.
PMID- 28694697
TI - Double bronchodilation in chronic obstructive pulmonary disease: a crude analysis
from a systematic review.
AB - OBJECTIVE: The combination of a long-acting muscarinic antagonist (LAMA) and a
long-acting beta2-agonist (LABA) in a single inhaler is a viable treatment option
for patients with chronic obstructive pulmonary disease (COPD). Here, we
systematically review the current knowledge on double bronchodilation for the
treatment of COPD, with a specific focus on its efficacy versus placebo and/or
monotherapy bronchodilation. METHODS: A systematic review of clinical trials
investigating LABA/LAMA combination therapies was conducted. Articles were
retrieved from PubMed, Embase, and Scopus on June 26, 2016. We specifically
selected clinical trials with a randomized controlled or crossover design
published in any scientific journal showing the following characteristics: 1)
comparison of different LABA/LAMA combinations in a single inhaler for patients
with COPD, 2) dose approved in Europe, and 3) focus on efficacy (versus placebo
and/or bronchodilator monotherapy) in terms of lung function, respiratory
symptoms, or exacerbations. RESULTS: We analyzed 26 clinical trials conducted on
24,338 patients. All LABA/LAMA combinations were consistently able to improve
lung function compared with both placebo and bronchodilator monotherapy.
Improvements in symptoms were also consistent versus placebo, showing some lack
of correlation for some clinical end points and combinations versus monotherapy
bronchodilation. Albeit being an exploratory end point, exacerbations showed an
improvement with LABA/LAMA combinations over placebo in some trials; however,
scarce information was available in comparison with bronchodilator monotherapy in
most studies. CONCLUSION: Our data show consistent improvements for LABA/LAMA
combinations, albeit with some variability (depending on the clinical end point,
the specific combination, and the comparison group). Clinicians should be aware
that these are average differences. All treatments should be tailored at the
individual level to optimize clinical outcomes.
PMID- 28694698
TI - Maintenance therapy in COPD: time to phase out ICS and switch to the new
LAMA/LABA inhalers?
AB - Long-term maintenance therapy for COPD is evolving rapidly. Dual bronchodilation
with new long-acting muscarinic antagonist and long-acting beta-agonist
(LAMA/LABA) fixed dose combination inhalers were introduced over the past 2
years. In clinical trials, these inhalers significantly improved lung function
(trough forced expiratory volume in 1 second), patient-reported outcomes, and
quality of life measures compared with placebo, their respective monocomponents,
and tiotropium. The recorded adverse events of these new inhalers were also
similar to those of their monocomponents or placebo. There are concerns regarding
long-term complications (weight gain, osteoporosis, cataract) and increased risk
of community-acquired pneumonia with the use of inhaled corticosteroids (ICS).
The new LAMA/LABA inhalers could potentially reduce the use of ICS as part and
parcel of maintenance therapy in COPD. Recent studies compared these LAMA/LABA
inhalers with ICS/LABA combination inhalers in moderate-to-severe COPD. The
results are promising and favor the LAMA/LABA inhalers, especially in the longer
duration trials. Furthermore, there is a clearer picture emerging as to the
subgroup of COPD patients who may be able to successfully switch from their
current ICS/LABA therapy to these new LAMA/LABA inhalers.
PMID- 28694699
TI - Antitumor HPV E7-specific CTL activity elicited by in vivo engineered exosomes
produced through DNA inoculation.
AB - We recently proved that exosomes engineered in vitro to deliver high amounts of
HPV E7 upon fusion with the Nefmut exosome-anchoring protein elicit an efficient
anti-E7 cytotoxic T lymphocyte immune response. However, in view of a potential
clinic application of this finding, our exosome-based immunization strategy was
faced with possible technical difficulties including industrial manufacturing,
cost of production, and storage. To overcome these hurdles, we designed an as yet
unproven exosome-based immunization strategy relying on delivery by intramuscular
inoculation of a DNA vector expressing Nefmut fused with HPV E7. In this way, we
predicted that the expression of the Nefmut/E7 vector in muscle cells would
result in a continuous source of endogenous (ie, produced by the inoculated host)
engineered exosomes able to induce an E7-specific immune response. To assess this
hypothesis, we first demonstrated that the injection of a Nefmut/green
fluorescent protein-expressing vector led to the release of fluorescent exosomes,
as detected in plasma of inoculated mice. Then, we observed that mice inoculated
intramuscularly with a vector expressing Nefmut/E7 developed a CD8+ T-cell immune
response against both Nef and E7. Conversely, no CD8+ T-cell responses were
detected upon injection of vectors expressing either the wild-type Nef isoform of
E7 alone, most likely a consequence of their inefficient exosome incorporation.
The production of immunogenic exosomes in the DNA-injected mice was formally
demonstrated by the E7-specific CD8+ T-cell immune response we detected in mice
inoculated with exosomes isolated from plasma of mice inoculated with the
Nefmut/E7 vector. Finally, we provide evidence that the injection of Nefmut/E7
DNA led to the generation of effective antigen-specific cytotoxic T lymphocytes
whose activity was likely part of the potent, therapeutic antitumor effect we
observed in mice implanted with TC-1 tumor cells. In summary, we established a
novel method to generate immunogenic exosomes in vivo by the intramuscular
inoculation of DNA vectors expressing the exosome-anchoring protein Nefmut and
its derivatives.
PMID- 28694700
TI - Role of SIRT1/PGC-1alpha in mitochondrial oxidative stress in autistic spectrum
disorder.
AB - Autistic spectrum disorder (ASD) is a neurodevelopmental disorder and has a high
prevalence in children. Recently, mitochondrial oxidative stress has been
proposed to be associated with ASD. Besides, SIRT1/PGC-1alpha signaling plays an
important role in combating oxidative stress. In this study, we sought to
determine the role of SIRT1/PGC-1alpha signaling in the ASD lymphoblastoid cell
lines (LCLs). In this study, the mRNA and protein expressions of SIRT1/PGC-1alpha
axis genes were assessed in 35 children with ASD and 35 healthy controls (matched
for age, gender, and IQ). An immortalized LCL was established by transforming
lymphocytes with Epstein-Barr virus. Next, we used ASD LCLs and control LCLs to
detect SIRT1/PGC-1alpha axis genes expression and oxidative damage. Finally, the
effect of overexpression of PGC-1alpha on oxidative injury in the ASD LCLs was
determined. SIRT1/PGC-1alpha axis genes expression was downregulated at RNA and
protein levels in ASD patients and LCLs. Besides, the translocation of cytochrome
c and DIABLO from mitochondria to the cytosol was found in the ASD LCLs.
Moreover, the intracellular reactive oxygen species (ROS) and mitochondrial ROS
and cell apoptosis were increased in the ASD LCLs. However, overexpression of PGC
1alpha upregulated the SIRT1/PGC-1alpha axis genes expression and reduced
cytochrome c and DIABLO release in the ASD LCLs. Also, overexpression of PGC
1alpha reduced the ROS generation and cell apoptosis in the ASD LCLs.
Overexpression of PGC-1alpha could reduce the oxidative injury in the ASD LCLs,
and PGC-1alpha may act as a target for treatment.
PMID- 28694701
TI - High levels of Nesfatin-1 in relation to the dysfunction of the hypothalamic
pituitary-adrenal and hypothalamus-pituitary-thyroid axes in depressed patients
with subclinical hypothyroidism.
AB - Despite the increasing amount of evidence suggesting a relationship between
depression and subclinical hypothyroidism (SCH), the exact mechanism underlying
this relationship remains unclear. The main purpose of this study was to
investigate the roles of plasma Nesfatin-1 levels and dysfunction of the
hypothalamic-pituitary-adrenal (HPA) and hypothalamus-pituitary-thyroid (HPT)
axes in the comorbidity of depression and SCH. Dysfunctions of the HPA and HPT
axes were detected by measuring plasma corticosterone and thyroid-stimulating
hormone (TSH) concentrations, respectively. Subjects in the patient group were
selected from patients hospitalized at the Anhui Mental Health Center, and
subjects in the control group were recruited from healthy volunteers. Healthy
control subjects were matched to the patients in terms of weight and body mass
index. The Hamilton Depression Rating Scale was administered to both the groups.
The enzyme-linked immunosorbent assay method was used to measure plasma Nesfatin
1, corticosterone, and TSH levels. A radioimmunoassay kit was used for the
measurement of the plasma-free triiodothyronine and plasma-free thyroxine. The
results showed that the Hamilton Depression Rating Scale scores and average
Nesfatin-1, corticosterone, and TSH levels were significantly higher in depressed
patients with SCH than in the control group. Moreover, positive relationships
were observed between Nesfatin-1 levels and the concentrations of corticosterone
(r=0.626, P<0.001) and TSH (r=0.229, P=0.036) in depressed patients with SCH.
These findings indicate that Nesfatin-1 is involved in the comorbidity of
depression and SCH, and the mechanism underlying this involvement might be
related to the dysfunction of the HPA and HPT axes.
PMID- 28694702
TI - The economic and humanistic costs of chronic lower back pain in Japan.
AB - BACKGROUND: Few data are available that provide estimates of the economic impact
of chronic lower back pain (CLBP) in Japan. The current study estimated the
patient burden and the direct and indirect medical costs associated with CLBP in
Japan using data from a large cross-sectional patient survey. CLBP was
hypothesized to be associated with a considerable burden of illness and a large
economic impact. METHODS: Study participants completed the Japan National Health
and Wellness Survey in 2014, which included measures of health-related quality of
life (HRQoL), work impairment, impairment to daily activities, and healthcare
service use. Data from those reporting CLBP (N=392) were contrasted against those
from matched controls without back pain, using age and sex-adjusted models.
RESULTS: CLBP patients reported significantly lower HRQoL relative to matched
controls. Age-and sex-adjusted models estimated mean annual per patient direct
and indirect costs attributable to CLBP to be Y1,820,297 ($15,239 or ?12,551) and
Y1,479,899 ($12,389 or ?10,203), respectively, with the majority of direct costs
related to hospital expenses (Y1,584,759, which is equivalent to $13,267 and
?10,927). In estimating the economic impact of CLBP on society, the CLBP
respondents were estimated to include 1,508,524 individuals when extrapolated to
the Japanese population (815,461 of them employed). Ultimately, this represented
approximately Y1.2 trillion ($10 billion and ?8.3 billion) per year in lost
productivity at the time of this study. CONCLUSION: This study of patients with
CLBP in Japan has shown it to be associated with a significant burden on patients
and to have a considerable negative impact on the Japanese economy primarily
driven by lost productivity. Further research on the effectiveness of
interventions to improve the outcomes of those with CLBP is warranted.
PMID- 28694703
TI - Secondary sclerosing cholangitis in critically ill patients: current
perspectives.
AB - Secondary sclerosing cholangitis (SSC) is a term used for a group of chronic
cholestatic disease affecting the intra- and/or extrahepatic biliary tree with
inflammation and progressive stricture formation, which can lead to biliary
cirrhosis. A newly recognized form of SSC is secondary sclerosing cholangitis in
critically ill patients (SSC-CIP). Pathogenesis is believed to involve ischemic
injury of intrahepatic bile ducts associated with prolonged hypotension,
vasopressors administration, and/or mechanical ventilation in patients treated in
the intensive care unit (ICU). Patients diagnosed with SSC-CIP have no prior
history of liver disease and no known pathologic process or injury responsible
for bile duct obstruction prior to ICU treatment. Reasons leading to ICU
treatment are many including multitrauma, burn injury, cardiac surgery, severe
pneumonia, other infections, or bleeding after abdominal surgery. Patients have
in common prolonged ICU admission. SSC-CIP is associated with rapid progression
to liver cirrhosis and poor survival with limited treatment options except a
liver transplantation. Transplant-free survival is around 17-40 months, which is
lower than in other SSC patients. During the initial stages of the disease, the
clinical symptoms and biochemical profile are not specific and easily missed.
Biliary casts formation may be considered pathognomonic for SSC-CIP since most
patients have them in early stages of the disease. Increased awareness and early
detection of the disease and its complications is considered to be crucial to
improve the poor prognosis.
PMID- 28694704
TI - Health care provider experience with canagliflozin in real-world clinical
practice: favorability, treatment patterns, and patient outcomes.
AB - PURPOSE: This study describes how health care providers approach canagliflozin
for the treatment of patients with type 2 diabetes mellitus (T2DM) in the real
world. PATIENTS AND METHODS: An Internet-based questionnaire was completed by 101
endocrinologists, 101 primary care physicians, and 100 nurse
practitioners/physician assistants (NP/PAs). Health care providers were required
to have experience prescribing or managing patients using canagliflozin to be
included in the study. Health care providers compared canagliflozin with other
T2DM medication classes on clinical characteristics, costs, and patient
satisfaction. Confidence in canagliflozin was also measured. Health care
providers reported their canagliflozin prescribing experience and good candidate
characteristics for treatment. Finally, providers reported on patient outcomes
among those receiving canagliflozin. All variables were compared across provider
type. RESULTS: Health care providers reported higher favorability for
canagliflozin for blood pressure and body weight compared with dipeptidyl
peptidase-4 (DPP-4) inhibitors and higher favorability for effect on blood
pressure, body weight, treatment satisfaction, and glycosylated hemoglobin
(HbA1c) compared with sulfonylureas (SUs), with differences observed for effect
on blood pressure. Health care providers reported being very/extremely confident
(55%-74%) with canagliflozin as a second-to fourth-line treatment. The top 3
characteristics reported by the providers, in terms of describing a good
candidate for canagliflozin, include those concerned about their weight,
insurance coverage/affordability, and avoiding injectable treatments. Finally,
providers reported often/always observing patients' lowering or controlling HbA1c
(82%-88%) and improvement in overall quality of life (QoL; 50%-53%) with
canagliflozin treatment. No differences were observed across provider type for
confidence, good candidate characteristics, or patient outcomes. CONCLUSION:
Health care providers reported favorable experiences with canagliflozin and
witnessed improvements in patients' clinical outcomes and QoL.
PMID- 28694705
TI - Management of malignant pleural effusion: challenges and solutions.
AB - Malignant pleural effusion (MPE) is a sign of advanced cancer and is associated
with significant symptom burden and mortality. To date, management has been
palliative in nature with a focus on draining the pleural space, with therapies
aimed at preventing recurrence or providing intermittent drainage through
indwelling catheters. Given that patients with MPEs are heterogeneous with
respect to their cancer type and response to systemic therapy, functional status,
and pleural milieu, response to MPE therapy is also heterogeneous and difficult
to predict. Furthermore, the impact of therapies on important patient outcomes
has only recently been evaluated consistently in clinical trials and cohort
studies. In this review, we examine patient outcomes that have been studied to
date, address the question of which are most important for managing patients, and
review the literature related to the expected value for money (cost
effectiveness) of indwelling pleural catheters relative to traditionally
recommended approaches.
PMID- 28694707
TI - Did the 2011 AAP recommendations on youth HIV testing change practice? Trends
from a large urban adolescent program.
AB - PURPOSE: The purpose of this study was to determine whether there is adherence to
the October 2011 American Academy of Pediatrics (AAP) recommendations for HIV
screening in a large urban adolescent program with availability of a publicly
funded program providing free, confidential, sexually transmitted infection (STI)
and HIV counseling and testing (then rapid or third generation HIV testing),
nested in the same adolescent clinic. METHODS: We conducted a retrospective chart
review of HIV screening trends among 13- to 24-year-old patients tested for HIV
during periods of January 2010 to June 2011 (18 months pre-AAP recommendations
period) and July 2011 to December 2012 (18-month period, which included 15 months
after the AAP recommendations). RESULTS: During the period of January 2010 to
June 2011, there were 22 tests/1,000 medical visits (N = 824 of 37,520 medical
visits), and during the period of July 2011 to December 2012, there were 27
tests/1,000 medical visits (N = 1,068 of 38,763 medical visits) (p < 0.0001, odds
ratio [OR] 1.26). The number of 13- to 18-year-old patients screened in the pre
AAP period was 150, compared to 297 in the second 18-month period (X 2 = 43.3, df
= 1, p < 0.0001). A summative risk profile score of 0-9 was created in the form
of a continuous variable, with a risk score of 0 for those with no risk factor
identified and 1 point for each risk behavior identified. The proportion of HIV
test clients with zero-specified risk (a risk score of "0") increased from 2010
to 2012. CONCLUSION: Release of the 2011 AAP HIV testing guidelines was
associated with a modest increase in HIV screening and a shift toward testing
younger people and away from risk-based screening.
PMID- 28694706
TI - Abnormalities in alternative splicing of angiogenesis-related genes and their
role in HIV-related cancers.
AB - Alternative splicing of mRNA leads to an increase in proteome biodiversity by
allowing the generation of multiple mRNAs, coding for multiple protein isoforms
of various structural and functional properties from a single primary pre-mRNA
transcript. The protein isoforms produced are tightly regulated in normal
development but are mostly deregulated in various cancers. In HIV-infected
individuals with AIDS, there is an increase in aberrant alternative splicing,
resulting in an increase in HIV/AIDS-related cancers, such as Kaposi's sarcoma,
non-Hodgkin's lymphoma, and cervical cancer. This aberrant splicing leads to
abnormal production of protein and is caused by mutations in cis-acting elements
or trans-acting factors in angiogenesis-related genes. Restoring the normal
regulation of alternative splicing of angiogenic genes would alter the expression
of protein isoforms and may confer normal cell physiology in patients with these
cancers. This review highlights the abnormalities in alternative splicing of
angiogenesis-related genes and their implication in HIV/AIDS-related cancers.
This allows us to gain an insight into the pathogenesis of HIV/AIDS-related
cancer and in turn elucidate the therapeutic potential of alternatively spliced
genes in HIV/AIDS-related malignancies.
PMID- 28694708
TI - Spiritual care may impact mental health and medication adherence in HIV+
populations.
AB - OBJECTIVE: To explore a potential role for spirituality in medication-related
needs assessment for integrated care in chronically ill populations. METHOD: A
systematic literature review was conducted to explore the impact of faith beliefs
on health and/or medication adherence in individuals with depression and/or
HIV+/AIDS. Retrospective electronic medical record review of adult HIV+ patients
of an urban primary care clinic with integrated mental health services was
conducted, with Substance Abuse and Mental Illness Symptoms Screener (SAMISS),
major depressive disorder (MDD) incidence over the preceding year, and history of
contact with a spiritual advisor. A convenience sample was interviewed to
qualitatively assess potential medication therapy management needs and medication
related problems. Another sample was examined utilizing the Daily Spiritual
Experience Scale. RESULTS: The literature reports positive influence on health
behaviors, coping and outcomes; and poor medication adherence and treatment
decisions due to patient passivity or resistance. Spiritual advisor contact (not
limited to a specific religion) was significantly associated with MDD absence
(1.7% vs. 15.3%, P<0.005) and inversely related to SAMISS, depression, and poor
health behaviors. Patient interviews reflected significance of faith in terms of
insight and acceptance of illness, the role or need for medications, coping, and
medication adherence. An illustrative model was designed based on the literature
and data collection. CONCLUSION: Spiritual assessment may help identify positive
or negative influence on health. Spiritual interventions could be beneficial in
promoting adherence and positive health outcomes. Further research is
recommended.
PMID- 28694709
TI - The social stigma of HIV-AIDS: society's role.
AB - AIDS is a devastating and deadly disease that affects people worldwide and, like
all infections, it comes without warning. Specifically, childbearing women with
AIDS face constant psychological difficulties during their gestation period, even
though the pregnancy itself may be normal and healthy. These women have to deal
with the uncertainties and the stress that usually accompany a pregnancy, and
they have to live with the reality of having a life-threatening disease; in
addition to that, they also have to deal with discriminating and stigmatizing
behaviors from their environment. It is well known that a balanced mental state
is a major determining factor to having a normal pregnancy and constitutes the
starting point for having a good quality of life. Even though the progress in
both technology and medicine is rapid, infected pregnant women seem to be missing
this basic requirement. Communities seem unprepared and uneducated to smoothly
integrate these people in their societies, letting the ignorance marginalize and
isolate these patients. For all the aforementioned reasons, it is imperative that
society and medical professionals respond and provide all the necessary support
and advice to HIV-positive child bearers, in an attempt to allay their fears and
relieve their distress. The purpose of this paper is to summarize the
difficulties patients with HIV infection have to deal with, in order to survive
and merge into society, identify the main reasons for the low public awareness,
discuss the current situation, and provide potential solutions to reducing the
stigma among HIV patients.
PMID- 28694710
TI - Modeling ecodevelopmental context of sexually transmitted disease/HIV risk and
protective behaviors among African-American adolescents.
AB - Risk and protective processes are integrated developmental processes that
directly or indirectly affect behavioral outcomes. A better understanding of
these processes is needed, in order to gauge their contribution to sexual risk
behaviors. This retrospective cross-sectional study modeled the ecodevelopmental
chain of relationships to examine the social contexts of African-American (AA)
adolescents associated with sexually transmitted disease (STD)- and HIV-risk
behaviors. We used data from 1,619 AA adolescents with an average age of 16+/-1.8
years obtained from the first wave of the National Longitudinal Study of
Adolescent Health for this study. Confirmatory factor analysis followed by
structural equation modeling was conducted to identify the latent constructs that
reflect the social-interactional components of the ecodevelopmental theory. Among
contextual factors, findings indicated that a feeling of love from father,
school, religion, and parent attitudes toward adolescent sexual behavior were all
factors that played significant roles in the sexual behavior of AA adolescents.
AA adolescents who reported feeling love from their father, feeling a strong
negative attitude from their parents toward having sex at a very young age, and
having a strong bond with school personnel were associated with better health
statuses. The level of parents' involvement in their children's lives was
reflected in the adolescents' feeling of love from parents and moderated by their
socioeconomic status. Being male, attaining increased age, and being a sexual
minority were associated with higher likelihood of exhibiting risky sexual
behavior. In contrast, higher socioeconomic status and fathers' level of
involvement were indirectly associated with reduced STD/HIV-related sexual risk
behavior. In conclusion, our findings suggest that interventions aimed at maximal
protection against STD/HIV-related risk behavior among AA adolescents should
adopt both self- and context-based strategies that promote positive functioning
in the family, school, and peer microsystems.
PMID- 28694711
TI - Intention toward condom use and its associated factors among students of Debre
Work Senior Secondary and Preparatory School, East Gojjam Zone, Amhara Region,
Ethiopia.
AB - OBJECTIVE: The main aim of this research was to investigate the students'
intention toward condom use and associated factors among students in Debre Work
Secondary and Preparatory School, 2015. METHODS: A survey was carried out in the
high school and the preparatory school. The self-administered semistructured
questionnaire was distributed to 422 students. Systematic sampling techniques
were employed to each class. Data were entered and analyzed by using SPSS version
20.0 software. Descriptive and analytical data analysis and presentation were
used. Logistic regression model was used to check independent associations.
RESULT: Most (80.8%) of the respondents were not married. More than half (53.0%
and 52.3%) of the respondents had low perceived benefit and low perceived self
efficacy of using condom. About 46.79% of respondents had an interest in using
condoms and the rest had no intention. Males were 1.96 times more likely to have
intention to use condom compared to females (adjusted odds ratio [AOR], 95%
confidence interval [CI] 1.96 [1.29, 2.99]). When the intention to use condoms
was compared, married respondents were 2.41 times more likely than those who were
not married (AOR, 95% CI 2.41 [1.41, 4.14]). Intention to use condoms among
respondents who had high perceived benefit of using condom were 1.57 times more
compared to those who had low perceived benefit of using condom (AOR, 95% CI 1.57
[1.03, 2.39]). Intention to use condoms among those who had high perceived self
efficacy on condom use was 4.37 times higher compared to those who had low
perceived self-efficacy (AOR, 95% CI 4.37 [2.85, 6.71]). CONCLUSION: The level of
intention to use condoms among students of Debre Work Senior Secondary and
Preparatory School was low. Sex, current marital status, perceived benefit of
using condom, and perceived self-efficacy on condom use were the most positive
contributing factors for intention to condom use.
PMID- 28694712
TI - Creating physicians of the 21st century: assessment of the clinical years.
AB - Medical education has been under a constant state of revision for the past
several years. The overarching theme of the curriculum revisions for medical
schools across the USA has been creating better physicians for the 21st century,
with the same end result: graduating medical students at the optimal performance
level when entering residency. We propose a robust, thorough assessment process
that will address the needs of clerkships, residents, students, and, most
importantly, medical schools to best measure and improve clinical reasoning
skills that are required for the learning outcomes of our future physicians. The
Accreditation Council for Graduate Medical Education (ACGME) evaluates and
accredits medical school graduates based on competency-based outcomes and the
assessment of specialty-specific milestones; however, there is some evidence that
medical school graduates do not consistently meet the Level 1 milestones prior to
entering/beginning residency, thus starting their internship year underprepared
and overwhelmed. Medical schools should take on the responsibility to provide
competency-based assessments for their students during the clinical years. These
assessments should be geared toward preparing them with the cognitive
competencies and skills needed to successfully transition to residency. Then,
medical schools can produce students who will ultimately be prepared for
transition to their residency programs to provide quality care.
PMID- 28694713
TI - An Algorithmic Approach for Assessment of Mediastinal Lesions Using Conventional
Transbronchial Needle Aspiration and Endoscopic Ultrasonography in a Single
Procedure.
AB - BACKGROUND: In the era of endobronchial/esophageal ultrasound (EBUS-TBNA/EUS
FNA), many centers forgo conventional transbronchial needle aspiration (C-TBNA)
in favour of EBUS-TBNA/EUS-FNA despite no conclusive evidence showing better
yields with EBUS-TBNA/EUS-FNA. OBJECTIVES: Assess the feasibility of an
algorithmic approach for mediastinal sampling beginning with C-TBNA utilizing
rapid onsite cytologic evaluation. METHODS: Descriptive analysis of 92
consecutive patients referred for adenopathy that underwent C-TBNA and subsequent
EBUS-TBNA/EUS-FNA if C-TBNA was negative or nondiagnostic. RESULTS: 92 procedures
were analyzed. In 50 (54.3%) of cases, C-TBNA alone was sufficient. EBUS-TBNA was
performed after C-TBNA in 27 (29.3%) of cases and EUS-FNA in 33 (35.9%) of cases.
The yield was 92.9% for C-TBNA, 92.5% for EBUS-TBNA, and 89.7% for EUS-FNA. There
were no statistically significant differences in yields by LN station (P = 0.51),
the relationship between yield and LN size (P = 0.37), or time difference in
procedures following the algorithm compared to EBUS/EUS only procedures (33.7
minutes versus 32.4 minutes on average [95% CI for difference: -9.1 to 11.7], P =
0.80). CONCLUSIONS: An algorithmic approach to assess the mediastinum using C
TBNA initially is feasible without sacrificing yield or procedure times. C-TBNA
was sufficient for diagnosis in 54.3% of cases and can be efficiently taught in
an IP training program.
PMID- 28694714
TI - Sensitivity, Specificity, Predictive Values, and Accuracy of Three Diagnostic
Tests to Predict Inferior Alveolar Nerve Blockade Failure in Symptomatic
Irreversible Pulpitis.
AB - INTRODUCTION: The inferior alveolar nerve block (IANB) is the most common
anesthetic technique used on mandibular teeth during root canal treatment. Its
success in the presence of preoperative inflammation is still controversial. The
aim of this study was to evaluate the sensitivity, specificity, predictive
values, and accuracy of three diagnostic tests used to predict IANB failure in
symptomatic irreversible pulpitis (SIP). METHODOLOGY: A cross-sectional study was
carried out on the mandibular molars of 53 patients with SIP. All patients
received a single cartridge of mepivacaine 2% with 1 : 100000 epinephrine using
the IANB technique. Three diagnostic clinical tests were performed to detect
anesthetic failure. Anesthetic failure was defined as a positive painful response
to any of the three tests. Sensitivity, specificity, predictive values, accuracy,
and ROC curves were calculated and compared and significant differences were
analyzed. RESULTS: IANB failure was determined in 71.7% of the patients. The
sensitivity scores for the three tests (lip numbness, the cold stimuli test, and
responsiveness during endodontic access) were 0.03, 0.35, and 0.55, respectively,
and the specificity score was determined as 1 for all of the tests. Clinically,
none of the evaluated tests demonstrated a high enough accuracy (0.30, 0.53, and
0.68 for lip numbness, the cold stimuli test, and responsiveness during
endodontic access, resp.). A comparison of the areas under the curve in the ROC
analyses showed statistically significant differences between the three tests (p
< 0.05). CONCLUSION: None of the analyzed tests demonstrated a high enough
accuracy to be considered a reliable diagnostic tool for the prediction of
anesthetic failure.
PMID- 28694715
TI - Cancer Pain Management and Pain Interference with Daily Functioning among Cancer
Patients in Gondar University Hospital.
AB - Cancer is an increasing public health burden for Ethiopia. Pain is among the most
common symptoms in patients with cancer. Hence, we aimed to assess cancer pain
prevalence, cancer pain interference, and adequacy of cancer pain treatment in
the oncology ward of an Ethiopian teaching hospital. Of 83 patients, total of 76
(91.6%) cancer patients experienced pain with varying degree of severity, and 7
(8.4%) patients experienced severe pain. Of the 76 cancer patients with pain, 68
(89.2%) experienced pain interference with their daily activities. Fifty-four
(65%) patients were receiving inadequate cancer pain treatment with negative Pain
Management Index. Therefore, it is vital to anticipate and assess pain of the
cancer patients as routine clinical practice, to optimize analgesic therapy, and
to identify and overcome barriers to adequate pain management.
PMID- 28694716
TI - Transparency and public accessibility of clinical trial information in Croatia:
how it affects patient participation in clinical trials.
AB - INTRODUCTION: Despite increased visibility of clinical trials through
international trial registries, patients often remain uninformed of their
existence, especially if they do not have access to adequate information about
clinical research, including the language of the information. The aim of this
study was to describe the context for transparency of clinical trials in Croatia
in relation to countries in Central and Eastern Europe, and to assess how
informed Croatian patients are about clinical trials and their accessibility.
MATERIALS AND METHODS: We assessed the transparency of clinical trials from the
data available in the public domain. We also conducted an anonymous survey on a
convenience sample of 257 patients visiting two family medicine offices or an
oncology department in south Croatia, and members of national patients'
associations. RESULTS: Despite legal provisions for transparency of clinical
trials in Croatia, they are still not sufficiently visible in the public domain.
Among countries from Central and Eastern Europe, Croatia has the fewest number of
registered trials in the EU Clinical Trials Registry. 66% of the patients in the
survey were aware of the existence of clinical trials but only 15% were informed
about possibilities of participating in a trial. Although 58% of the respondents
were willing to try new treatments, only 6% actually participated in a clinical
trial. Only 2% of the respondents were aware of publicly available trial
registries. CONCLUSIONS: Our study demonstrates that there is low transparency of
clinical trials in Croatia, and that Croatian patients are not fully aware of
clinical trials and the possibilities of participating in them, despite reported
availability of Internet resources and good communication with their physicians.
There is a need for active policy measures to increase the awareness of and
access to clinical trials to patients in Croatia, particularly in their own
language.
PMID- 28694717
TI - Predatory journals and their effects on scientific research community.
PMID- 28694718
TI - What I learned from predatory publishers.
AB - This article is a first-hand account of the author's work identifying and listing
predatory publishers from 2012 to 2017. Predatory publishers use the gold (author
pays) open access model and aim to generate as much revenue as possible, often
foregoing a proper peer review. The paper details how predatory publishers came
to exist and shows how they were largely enabled and condoned by the open-access
social movement, the scholarly publishing industry, and academic librarians. The
author describes tactics predatory publishers used to attempt to be removed from
his lists, details the damage predatory journals cause to science, and comments
on the future of scholarly publishing.
PMID- 28694719
TI - Ethical issues in publishing in predatory journals.
AB - Predatory journals, or journals that charge an article processing charge (APC) to
authors, yet do not have the hallmarks of legitimate scholarly journals such as
peer review and editing, Editorial Boards, editorial offices, and other editorial
standards, pose a number of new ethical issues in journal publishing. This paper
discusses ethical issues around predatory journals and publishing in them. These
issues include misrepresentation; lack of editorial and publishing standards and
practices; academic deception; research and funding wasted; lack of archived
content; and undermining confidence in research literature. It is important that
the scholarly community, including authors, institutions, editors, and
publishers, support the legitimate scholarly research enterprise, and avoid
supporting predatory journals by not publishing in them, serving as their editors
or on the Editorial Boards, or permitting faculty to knowingly publish in them
without consequences.
PMID- 28694720
TI - Identifying predatory or pseudo-journals.
PMID- 28694721
TI - Does small equal predatory? Analysis of publication charges and transparency of
editorial policies in Croatian open access journals.
AB - INTRODUCTION: We approach the problem of "predatory" journals and publishers from
the perspective of small scientific communities and small journals that may
sometimes be perceived as "predatory". Among other characteristics of "predatory"
journals two most relevant are their business model and the quality of the
editorial work. MATERIALS AND METHODS: We analysed 444 Croatian open access (OA)
journals in the Hrcak (portal of Croatian scientific journals) digital journal
repository for the presence of article processing charges as a business model and
the transparency of editorial policies. RESULTS: The majority of journals do not
charge authors or require submission or article processing charges, which clearly
distinguishes them from "predatory" journals. Almost all Hrcak OA journals have
publicly available information on editorial boards, including full names and
affiliations, and detailed contact information for the editorial office at the
Hrcak website. The journal names are unique and cannot be easily confused with
another journal or intend to mislead about the journal's origin. While most
journals provide information on peer review process, many do not provide
guidelines for reviewers or other editorial and publication ethics standards.
CONCLUSION: In order to clearly differentiate themselves from predatory journals,
it is not enough for journals from small research communities to operate on non
commercial bases, but also to have transparent editorial policies.
PMID- 28694722
TI - Thyroid testing in acutely ill patients may be an expensive distraction.
AB - In health, an efficient negative feedback mechanism maintains serum thyroid
hormone concentrations within an exquisitely controlled narrow range. Therefore
any change that occurs to thyroid hormones in intrinsic thyroid disease is
concordant and easy to interpret. Optimal functioning of the many tissues they
influence is thereby facilitated.?The situation in acute illnesses is different.
Mechanisms that operate in these circumstances influence the hypothalamic
pituitary-thyroid axis and its components producing thyroid test results, which
are discordant, do not fit recognizable patterns and are difficult to interpret.
The yield of abnormalities is also low (about 7%). As many studies indicate,
thyroid tests are expensive and consume large amounts of the hospital budget and
resources of hospital laboratories. Other studies have shown that when
abnormalities are detected, clinicians do not intervene or follow up these
subjects. Therefore the clinical utility of thyroid testing in acutely ill
patients is debatable. Interventions to change requestor behaviour with regard to
thyroid testing in acutely ill subjects and the success of some audit and
educational interventions are worthy of note.?Thyroid testing in acutely ill
patients is often an expensive distraction and is of limited clinical value.
Targeted thyroid testing should be offered in this group only to those with: (a)
symptoms or signs of thyroid disease e.g. goiter or orbitopathy; (b) risk factors
for thyroid disease, previous or family history of thyroid disease;
PMID- 28694723
TI - Does recreational scuba diving have clinically significant effect on routine
haematological parameters?
AB - INTRODUCTION: Scuba diving represents a combination of exercise and changes in
environmental conditions. This study aimed to evaluate changes in haematological
parameters after recreational scuba diving in order to identify clinically
significant changes. MATERIALS AND METHODS: The study included males, 17
recreational divers, median age (range) 41 (30-52) years. Blood samples were
taken before diving, immediately after diving to 30 meters for 30 minutes, 3
hours and 6 hours after diving. Complete blood counts were analyzed on the Cell
Dyn Ruby haematology analyzer. Statistical significance between successive
measurements was tested using Friedman test. The difference between the two
measurements was judged against desirable bias (DSB) derived from biological
variation and calculated reference change values (RCV). The difference higher
than RCV was considered clinically significant. RESULTS: A statistically
significant increase and difference judging against DSB was observed: for
neutrophils immediately, 3 and 6 hours after diving (18%, 34% and 36%,
respectively), for white blood cells (WBCs) 3 and 6 hours after diving (20% and
25%, respectively), for lymphocytes (20%) and monocytes (23%) 6 hours after
diving. A statistically significant decrease and difference judging against DSB
was found: immediately after diving for monocytes (- 15%), 3 and 6 hours after
diving for red blood cells (RBCs) (- 2.6% and -2.9%, respectively), haemoglobin (
2.1% and - 2.8%, respectively) and haematocrit (- 2.4% and - 3.2%,
respectively). A clinically significant change was not found for any of the test
parameters when compared to RCV. CONCLUSIONS: Observed statistically significant
changes after recreational scuba diving; WBCs, neutrophils, lymphocytes,
monocytes increase and RBCs, haemoglobin, haematocrit decrease, probably will not
affect clinical decision.
PMID- 28694724
TI - Evaluation of new Beckman Coulter 25(OH) Vitamin D assay and potential
improvement of clinical interpretation.
AB - INTRODUCTION: The aim of this study was to assess the analytical performances of
the newly developed Access2 25-hydroxyvitamin D (25(OH)D) total immunoassay on
two analysers, DxI800 and Access2 (Beckman Coulter, Brea, CA, USA), and compare
these two and a recalibrated Modular E 170 25(OH)D assay (Roche Diagnostics,
Penzberg, Germany) with reference liquid chromatography tandem-mass spectrometry
(LC-MS/MS) with special emphasis on clinical diagnosis. MATERIALS AND METHODS:
Beckman immunoassays were assessed for imprecision, accuracy, limit of blank
(LoB), limit of detection (LoD), limit of quantitation (LoQ), linearity,
interference, and carryover. One hundred and nineteen samples were run on DxI
800, Access2, and E 170, and agreement with the LC-MS/MS method was evaluated.
RESULTS: DxI 800 and Access2 assays showed good performances in terms of LoB,
LoD, LoQ, linearity, and interference. All immunoassays showed negative biases
ranging from - 8.6% (DxI 800) to - 19.2% (Access2). DxI 800 and Access2 systems
had proportional biases, and the E170 system had a constant bias with the largest
random error. Concordance correlation coefficient values ranged from 0.941 (CI:
0.917-0.958) for DxI800 to 0.854 (CI: 0.811-0.889) for Access2. Kappa (kappa)
coefficients were found moderate for Dxl (0.709; CI: 0.581-0.837) and E170
(0.771; CI: 0.587-0.844) and fair for Access2 (0.572; CI: 0.428-0.716).
CONCLUSIONS: All immunoassays can be used in routine 25(OH)D measurements, still
fairly diagnosing patients' status. Recent standardization attempts seem not to
contribute too much to clinical diagnosis. A clinical laboratory must at least be
aware of its method to avoid misinterpretation of results.
PMID- 28694725
TI - Impact of reference change value (RCV) based autoverification on turnaround time
and physician satisfaction.
AB - BACKGROUND: For a quicker delivery of laboratory test results to the hospital
emergency department (ED), we implemented an autoverification system based on the
reference change value (RCV). The aim of this study was to assess how the RCV
based autoverification reflected on turnaround time (TAT) and on physician
satisfaction. MATERIALS AND METHODS: The laboratory information system (LIS) was
programmed to autoverify the results as long as they were within the range
settled by RCV, so that the autoverified results were reported to the physician
as soon as the tests were carried out, without any further intervention. We
analyzed the same three-month periods' TAT and verification time (VFT) from the
years prior to and following the implementation of RCV autoverification. The
change in physicians' satisfaction levels was assessed using the hospital's
Annual Physician Satisfaction Survey (APSS). Over sixty percent of physicians
completed the questionnaire, and the amount of daily ED test requests (nearly
three hundred) did not vary throughout the duration of this study. RESULTS: Mann
Whitney U test showed that the VFT was significantly reduced in all the test but
troponin I. There were substantial reductions in TAT medians (haemogram, 75%;
fibrinogen, 41%; prothrombin time, 40%; sodium, 27%). The percentage of
physicians satisfied with the haematological and biochemical tests' TAT increased
from 84% to 93% and from 86% to 91% respectively. CONCLUSIONS: Our results reveal
that VFT and TAT were severely reduced in most emergency tests, greatly improving
physicians' satisfaction with TAT.
PMID- 28694726
TI - A nationwide multicentre study in Turkey for establishing reference intervals of
haematological parameters with novel use of a panel of whole blood.
AB - INTRODUCTION: A nationwide multicentre study was conducted to establish well
defined reference intervals (RIs) of haematological parameters for the Turkish
population in consideration of sources of variation in reference values (RVs).
MATERIALS AND METHODS: K2-EDTA whole blood samples (total of 3363) were collected
from 12 laboratories. Sera were also collected for measurements of iron, UIBC,
TIBC, and ferritin for use in the latent abnormal values exclusion (LAVE) method.
The blood samples were analysed within 2 hours in each laboratory using Cell Dyn
and Ruby (Abbott), LH780 (Beckman Coulter), or XT-2000i (Sysmex). A panel of
freshly prepared blood from 40 healthy volunteers was measured in common to
assess any analyser-dependent bias in the measurements. The SD ratio (SDR) based
on ANOVA was used to judge the need for partitioning RVs. RIs were computed by
the parametric method with/without applying the LAVE method. RESULTS: Analyser
dependent bias was found for basophils (Bas), MCHC, RDW and MPV from the panel
test results and thus those RIs were derived for each manufacturer. RIs were
determined from all volunteers' results for WBC, neutrophils, lymphocytes,
monocytes, eosinophils, MCV, MCH and platelets. Gender-specific RIs were required
for RBC, haemoglobin, haematocrit, iron, UIBC and ferritin. Region-specific RIs
were required for RBC, haemoglobin, haematocrit, UIBC, and TIBC. CONCLUSIONS:
With the novel use of a freshly prepared blood panel, manufacturer-specific RIs'
were derived for Bas, Bas%, MCHC, RDW and MPV. Regional differences in RIs were
observed among the 7 regions of Turkey, which may be attributed to nutritional or
environmental factors, including altitude.
PMID- 28694727
TI - Labile glycated haemoglobin and carbamylated haemoglobin are still critical
points for HbA1c measurement.
AB - INTRODUCTION: Haemoglobin A1c (HbA1c) is a key analyte for the monitoring of
glycemic balance in diabetic patients and is used for diabetes diagnosis in many
countries. The potential interference of carbamylated haemoglobin (cHb) and
labile glycated haemoglobin (LA1c) on HbA1c assays must remain a matter of
vigilance. Such a situation has occurred in our laboratory with a kit replacement
on the Bio-Rad VariantTM II testing system, a cation-exchange high performance
liquid chromatography (HPLC) system. With this method, LA1c and cHb coeluted in a
same peak which may have different consequences on HbA1c values. MATERIALS AND
METHODS: The influence of increasing LA1c and cHb values on HbA1c results was
studied with in vitro glycation and carbamylation of samples. Samples from
patients with high and normal blood urea concentrations were assayed by HPLC and
immunological assay. RESULTS: We observed that the degree of interference greatly
varied depending on the nature of the interfering Hb fractions found under the so
called "LA1c peak". Thus, we have decided to apply a decision tree using "LA1c"
thresholds depending on: (i) the retention time, (ii) the shape of the peak,
(iii) other analytes, like urea. If the peak recognized as "LA1c" is mainly
formed by LA1c, we consider that there is no interference until 4%. If the peak
is mainly formed by cHb, we consider an interference threshold equal to 2%.
CONCLUSIONS: This situation reminds that cHb and LA1c remain critical issues in
chromatography-based HbA1c assays and that adapted criteria must be set up for
result interpretation.
PMID- 28694728
TI - Evaluation of staff performance and interpretation of the screening program for
prevention of thalassemia.
AB - INTRODUCTION: Thalassemia screening program has been implemented for years in
Southeast Asia, but no external quality assessment program has been established.
We have developed and initiated the proficiency testing (PT) program for the
first time in Thailand with the aim to assess the screening performance of
laboratory staff and their competency in interpretation of the screening results.
MATERIALS AND METHODS: Three PT cycles per year were organized. From the first to
the third cycle of the PT scheme, a total number of participant laboratories
increased from 59 to 67. In each cycle, 2 PT items (assigned as blood samples of
the couple) were provided. Performance evaluation was based on the accuracy of
screening results, i.e. mean corpuscular volume (MCV), mean corpuscular
haemoglobin (MCH) and the dichlorophenolindophenol (DCIP) test for haemoglobin E,
including the competency in interpretation of screening results and assessment of
foetal risk. Performance was assessed by comparing the participants' result
against the assigned value. RESULTS: Of all 3 cycles, most laboratories reported
acceptable MCV and MCH values. From the first to the third cycle, incorrect DCIP
test and misinterpretation rates were decreased while incorrect risk assessment
varied by cycle to cycle. Combining the accuracy of thalassemia screening and the
competency in interpretation and risk assessment, approximately half of
participants showed excellent performance. CONCLUSION: Improved performance
observed in many laboratories reflects the achievement and benefit of the PT
program which should be regularly provided.
PMID- 28694729
TI - The alcohol used for cleansing the venipuncture site does not jeopardize blood
and plasma alcohol measurement with head-space gas chromatography and an
enzymatic assay.
AB - INTRODUCTION: This study aimed to establish whether an alcoholic antiseptic,
wiped or not before venipuncture, may jeopardize alcohol testing with a
commercial enzymatic assay and a reference head-space gas chromatography (GC)
technique. MATERIALS AND METHODS: Venous blood was collected from 23 healthy
volunteers, with two sequential procedures. In the first blood collection, 2 mL
of alcoholic antiseptic (0.5% chlorhexidine, 70% ethanol) were place on a gauge
pad, the venipuncture site of right arm was cleaned but the antiseptic was not
let to dry before phlebotomy. In the second blood collection, 2 mL of the same
alcoholic antiseptic were placed on another gauge pad, the venipuncture site of
left harm was cleaned and the antiseptic was accurately cleansed before
phlebotomy. Ethanol was measured with a reference GC technique in whole blood and
EDTA plasma, and a commercial enzymatic assay in EDTA plasma. RESULTS: No subject
complained about feeling a particular itchy sensation when the alcohol was not
wiped before puncturing the vein. The concentration of alcohol in all EDTA plasma
samples was always lower than the limit of detection of the enzymatic assay
(i.e., 2.2 mmol/L; 0.1 g/L). Similarly, alcohol concentration was also
undetectable using a reference GC technique (i.e., < 0.22 mmol/L; 0.01 g/L) in
EDTA plasma and whole blood. CONCLUSION: It seems reasonable to conclude that
using ethanol-containing antiseptics before venipuncture may not be causes of
spurious or false positive results of alcohol measurement at least when ideal
venipunctures can be performed.
PMID- 28694730
TI - Topiramate induced metabolic acidosis and kidney stones - a case study.
AB - INTRODUCTION: The aim of this study is to present a case of 44 years old woman
with topiramate induced metabolic acidosis and kidney stones. MATERIALS AND
METHODS: The laboratory features of topiramate caused renal tubular acidosis in
blood and urine during topiramate treatment, with correction of metabolic
acidosis by potassium citrate, and after topiramate withdrawal are presented.
Differential diagnosis of all possible causes of metabolic acidosis is discussed.
RESULTS: The results revealed negative base excess in extracellular fluid of -
9.2 mmol/L, low serum HCO3- concentration (18.6 mmol/L), trend to alkaline urine
(pH 6.39) and low urine citrate concentration (0.3 mmol/24h). After topiramate
withdrawal, all parameters of the internal environment normalized. CONCLUSIONS:
This study has shown that long-term topiramate administration could induce
metabolic acidosis and consequently urholithiasis. Thus, we could recommend
testing blood acid base balance, urinary pH and citrates in patients taking
topiramate and suffering from kidney stones.
PMID- 28694731
TI - Detection of let-7 miRNAs in urine supernatant as potential diagnostic approach
in non-metastatic clear-cell renal cell carcinoma.
AB - INTRODUCTION: Urinary microRNAs (miRNAs) are emerging as a clinically useful tool
for early and non-invasive detection of various types of cancer. The aim of this
study was to evaluate whether let-7 family miRNAs differ in their urinary
concentrations between renal cell carcinoma (RCC) cases and healthy controls.
MATERIALS AND METHODS: In the case-control study, 69 non-metastatic clear-cell
RCC patients and 36 gender/age-matched healthy controls were prospectively
enrolled. Total RNA was purified from cell-free supernatant of the 105 first
morning urine specimens. Let-7 family miRNAs were determined in cell-free
supernatant using quantitative miRNA real-time reverse-transcription PCR and
absolute quantification approach. RESULTS: Concentrations of all let-7 miRNAs
(let-7a, let-7b, let-7c, let-7d, let-7e and let-7g) were significantly higher in
urine samples obtained from RCC patients compared to healthy controls (P < 0.001;
P < 0.001; P = 0.005; P = 0.006; P = 0.015 and P = 0.002, respectively).
Subsequent ROC analysis has shown that let-7a concentration possesses good
ability to differentiate between cases and controls with area under curve being
0.8307 (sensitivity 71%, specificity 81%). CONCLUSIONS: We have shown that let-7
miRNAs are abundant in the urine samples of patients with clear-cell RCC, and out
of six let-7 family members, let-7a outperforms the others and presents promising
non-invasive biomarker for the detection of RCC.
PMID- 28694732
TI - Biochemia Medica introduces new section: Pre-analytical mysteries.
PMID- 28694733
TI - Acutely developing, spurious anaemia without actual blood loss. A paradigmatic
case report.
AB - We describe the case of a 55-year old women admitted at night to the emergency
department (ED), complaining for acute abdominal pain lasting for nearly 5 hours.
A first blood testing, performed immediately after admission, revealed mild
anaemia. A second blood sample, drawn two hours after admission, revealed a
considerable decrease of haemoglobin, haematocrit, total white blood cell and
platelet counts (between 10-15% reduction). Abdominal ultrasonography was normal
and the patient had no signs or symptoms of internal or external haemorrhage. Pre
analytical and analytical errors were accurately excluded. No infusion therapy
was administered. After thoughtful discussing the sequence of events, it was
ascertained that the first set of blood samples was drawn with the patient in
seated position, immediately after ED admission (i.e., approximately 1 min passed
from standing to seated position before venipuncture), whereas the second set of
blood samples was drawn with the patient lying for two hours in supine position.
This case report highlights the importance of standardizing patient position
before venous blood collection, along with the crucial role played by cooperation
and communication between laboratory and clinical wards for identifying and
troubleshooting potential causes of spurious results of in vitro diagnostic
testing.
PMID- 28694734
TI - Case report of unexplained hypocalcaemia in a slightly haemolysed sample.
AB - The case presented highlights a common pre-analytical problem identified in the
laboratory that was initially missed. It concerns a young, generally healthy
adult patient with no significant medical history and no significant family
history. They presented with common flu like symptoms to their primary care
clinician who considered this was most likely a viral problem that would pass
with time. The clinician, however, did some routine bloods to reassure the
patient despite a lack of clinical indication. When the sample was analysed the
sample was haemolysed with strikingly low calcium. This led to the patient being
called into hospital for urgent repeat investigations, all of which turned out to
be within normal ranges. On further investigation the original sample was found
to be contaminated. This result would normally have been flagged but was missed
due to the complication of haemolysis.
PMID- 28694735
TI - What's floating on my plasma?
AB - We report on a preanalytical issue we encountered during routine clinical
chemistry analyses, potentially leading to deviated analysis results and believe
that it might help other laboratories to overcome similar problems. In a heparin
gel tube we measured an implausible glucose value of 0.06 mmol/L. Re-measurement
of the same sample resulted in a glucose value of 5.4 mmol/L. After excluding an
analytical error, we inspected the sample closer and found a white material as
well as fatty droplets floating on the surface of the plasma tube. Evaluation of
these structures revealed that the white particulate matter (WPM) consisted of
fibrinogen, platelets and leukocytes and the fatty droplets most probably
originated from the separator gel. We concluded that these structures formed a
temporary clot in the instruments pipetting needle thereby altering the sampling
volume and subsequently the measured glucose value. The formation of WPM might be
attributable to high speed centrifugation, high cholesterol levels, the gel
formulation or a combination of several issues such as temperature, heparin
concentration, pH and patient-specific factors. The gel droplets were most
probably caused by an aberrant gel formulation in combination with an improper
storage of the empty tubes on the wards prior to phlebotomy. After adding an
additional instrument cleansing cycle and changing to another batch of heparin
tubes the problems could be significantly reduced.
PMID- 28694736
TI - The Digital Hood: Social Media Use among Youth in Disadvantaged Neighborhoods.
AB - This study examines the role of social media in the lives of youth living in
disadvantaged neighborhoods. Feminist Standpoint theory, which privileges the
voices of marginalized communities in understanding social phenomena, suggests
that youth at the margins have specific knowledge that helps us understand social
media more broadly. We conducted semi-structured interviews with 30 females and
30 males aged 13 to 24 about their social worlds and neighborhoods, both on- and
offline. The findings reveal a dynamic and somewhat concerning interplay between
the geographic neighborhood and the digital neighborhood, whereby negative social
interactions in the geographic neighborhood are reproduced and amplified on
social media.
PMID- 28694737
TI - Archaeal Diversity and CO2 Fixers in Carbonate-/Siliciclastic-Rock Groundwater
Ecosystems.
AB - Groundwater environments provide habitats for diverse microbial communities, and
although Archaea usually represent a minor fraction of communities, they are
involved in key biogeochemical cycles. We analysed the archaeal diversity within
a mixed carbonate-rock/siliciclastic-rock aquifer system, vertically from surface
soils to subsurface groundwater including aquifer and aquitard rocks. Archaeal
diversity was also characterized along a monitoring well transect that spanned
surface land uses from forest/woodland to grassland and cropland. Sequencing of
16S rRNA genes showed that only a few surface soil-inhabiting Archaea were
present in the groundwater suggesting a restricted input from the surface.
Dominant groups in the groundwater belonged to the marine group I (MG-I)
Thaumarchaeota and the Woesearchaeota. Most of the groups detected in the
aquitard and aquifer rock samples belonged to either cultured or predicted
lithoautotrophs (e.g., Thaumarchaeota or Hadesarchaea). Furthermore, to target
autotrophs, a series of 13CO2 stable isotope-probing experiments were conducted
using filter pieces obtained after filtration of 10,000 L of groundwater to
concentrate cells. These incubations identified the SAGMCG Thaumarchaeota and
Bathyarchaeota as groundwater autotrophs. Overall, the results suggest that the
majority of Archaea on rocks are fixing CO2, while archaeal autotrophy seems to
be limited in the groundwater.
PMID- 28694738
TI - "Can you keep it real?" : Practical, and culturally tailored lifestyle
recommendations by Mexican American women diagnosed with type 2 diabetes: A
qualitative study.
AB - BACKGROUND: The purpose of this article is to engage clinicians in a dialogue
about ideas on how to provide more specific, contextually relevant, practical and
culturally tailored diabetes self-management recommendations as suggested by
Mexican-American women diagnosed with type 2 diabetes. Current diabetes self
management recommendations, targeting Mexican Americans in particular, remain
largely broad ("reduce your calorie intake" or "cut back on carbs"), overly
ambitious ("stop eating tortillas"), and relatively ineffective (Svedbo Engstrom
et al., BMJ Open 6(3):e010249, 2016; Johansson et al., Int J Qual Stud Health
Well-being 11, 2016; Oomen et al., The Diabetes Educ 25:220-225, 1999; Franek,
Ont Health Technol Assess Ser 13(9):1-60, 2013; Purnell et al. Patient 9:349,
2016). METHODS: A secondary and focused analysis (N = 12) was performed on data
gathered from a larger qualitative study (N = 16), which explored diabetes among
Mexican-American women residing in rural South Texas. RESULTS: Findings from the
secondary analysis were that study informants elicited more realistic or
contextually relevant, specific self-management strategies that reflected the
cognitive, emotive, and behavioral areas but were reframed within the context of
the Mexican-American culture. Self-management strategies fell into the categories
of: (a) environmental controls, (b) avoiding overeating, (c) lifestyle changes,
(d) cooking tips, and (e) active self-management. CONCLUSIONS: Diabetes remains a
serious health threat to Mexican Americans, women in particular. Few individuals
attain glycemic control, likely due in part to the disconnect between global and
non-contextual self-management recommendations offered by health care providers
and the need for more detailed and realistic guidance required for the day-to-day
self-management of diabetes.
PMID- 28694741
TI - Role of matrix metalloproteinase 13 gene expression in the evaluation of
radiation response in oral squamous cell carcinoma.
AB - BACKGROUND: Matrix Metalloproteinase 13 (MMP13) is a member of collagenase family
and it is involved in the degradation of extracellular matrix and basement
membrane protein. It is thought to be associated with tumor invasion and
metastasis. Elevated MMP13 expression has been found in carcinoma of the breast,
urinary bladder, head and neck and others. It is observed that MMP13 gene is also
correlated with radiation response in OSCC (Oral squamous cell carcinoma) cell
line based study. The present study correlates the MMP13 expressions with
clinicopathological parameters and radiation response in OSCC patients. MATERIALS
AND METHODS: The MMP13 mRNA levels were determined by employing qRT-PCR (real
time quantitative reverse transcriptase-polymerase chain reaction). RESULTS: We
observed high expression of MMP13 mRNA in OSCC patients when compared with
matched controls. Statistically significant up regulation of MMP13 mRNA
expression was found in tobacco chewers, advanced T-stage (p < 0.001) and lymph
node metastasis (p < 0.01). MMP13 mRNA levels were also elevated in non
responders as compared to responders to radiation treatment. CONCLUSIONS: To the
best of our knowledge, this is the first report that indicates role of MMP13 in
radiation response in OSCC patients and could be used as potential bio-marker for
radiotherapy treatment in OSCC patients.
PMID- 28694740
TI - Review of hepatocellular carcinoma: Epidemiology, etiology, and carcinogenesis.
AB - Since the 1970s, the epidemic of hepatocellular carcinoma (HCC) has spread beyond
the Eastern Asian predominance and has been increasing in Northern hemisphere,
especially in the United States (US) and Western Europe. It occurs more commonly
in males in the fourth and fifth decades of life. Among all cancers, HCC is one
of the fastest growing causes of death in the US and poses a significant economic
burden on healthcare. Chronic liver disease due to hepatitis B virus or hepatitis
C virus and alcohol accounts for the majority of HCC cases. Incidence of
nonalcoholic fatty liver disease has been on the risem and it has also been
associated with the development of HCC. Its pathogenesis varies based on the
underlying etiological factor although majority of cases develop in the setting
of background cirrhosis. Carcinogenesis of HCC includes angiogenesis, chronic
inflammation, and tumor macroenvironment and microenvironment. There is a
significant role of both intrinsic genetic risk factors and extrinsic influences
such as alcohol or viral infections that lead to the development of HCC.
Understanding its etiopathogenesis helps select appropriate diagnostic tests and
treatments.
PMID- 28694739
TI - Chemotherapy and tumor microenvironment of pancreatic cancer.
AB - Pancreatic cancer is an extremely dismal malignance. Chemotherapy has been widely
applied to treat this intractable tumor. It has exclusive tumor microenvironment
(TME), characterized by dense desmoplasia and profound infiltrations of
immunosuppressive cells. Interactions between stromal cells and cancer cells play
vital roles to affect the biological behaviors of pancreatic cancer. Targeting
the stromal components of pancreatic cancer has shown promising results. In
addition to the direct toxic effects of chemotherapeutic drugs on cancer cells,
they can also remodel the TME, eventually affecting their efficacy. Herein, we
reviewed the following four aspects; (1) clinical landmark advances of
chemotherapy in pancreatic cancer, since 2000; (2) interactions and mechanisms
between stromal cells and pancreatic cancer cells; (3) remodeling effects and
mechanisms of chemotherapy on TME; (4) targeting stromal components in pancreatic
cancer.
PMID- 28694742
TI - Clinical validation of a blood-based classifier for diagnostic evaluation of
asymptomatic individuals with pulmonary nodules.
AB - BACKGROUND: The number of pulmonary nodules detected in the US is expected to
increase substantially following recent recommendations for nationwide CT-based
lung cancer screening. Given the low specificity of CT screening, non-invasive
adjuvant methods are needed to differentiate cancerous lesions from benign
nodules to help avoid unnecessary invasive procedures in the asymptomatic
population. We have constructed a serum-based multi-biomarker panel and assessed
its clinical accuracy in a retrospective analysis of samples collected from
participants with suspicious radiographic findings in the Prostate, Lung, Chest
and Ovarian (PLCO) cancer screening trial. METHODS: Starting with a set of 9
candidate biomarkers, we identified 8 that exhibited limited pre-analytical
variability with increasing clotting time, a key pre-analytical variable
associated with the collection of serum. These 8 biomarkers were evaluated in a
training study consisting of 95 stage I NSCLC patients and 186 smoker controls
where a 5-biomarker pulmonary nodule classifier (PNC) was selected. The clinical
accuracy of the PNC was determined in a blinded study of asymptomatic individuals
comprising 119 confirmed malignant nodule cases and 119 benign nodule controls
selected from the PLCO screening trial. RESULTS: A PNC comprising 5 biomarkers:
CEA, CYFRA 21-1, OPN, SCC, and TFPI, was selected in the training study. In an
independent validation study, the PNC resolved lung cancer cases from benign
nodule controls with an AUC of 0.653 (p < 0.0001). CEA and CYFRA 21-1, two of the
markers included in the PNC, also accurately distinguished malignant lesions from
benign controls. CONCLUSIONS: A 5-biomarker blood test has been developed for the
diagnostic evaluation of asymptomatic individuals with solitary pulmonary
nodules.
PMID- 28694743
TI - Interferon gamma induced compositional changes in human bone marrow derived
mesenchymal stem/stromal cells.
AB - BACKGROUND: Mesenchymal stem/stromal cells (MSC) display a range of
immunoregulatory properties which can be enhanced by the exposure to cytokines
such interferon gamma (IFN-gamma). However the compositional changes associated
with the 'licensing' of these cells have not been clearly defined. The present
study was undertaken to provide a detailed comparative proteomic analysis of the
compositional changes that occur in human bone marrow derived MSC following 20 h
treatment with IFN-gamma. METHODS: 2D LC MSMS analysis of control and IFN-gamma
treated cells from 5 different healthy donors provided confident identification
of more than 8400 proteins. RESULTS: In total 210 proteins were shown to be
significantly altered in their expression levels (>=|2SD|) following IFN-gamma
treatment. The changes for several of these proteins were confirmed by flow
cytometry. STRING analysis determined that approximately 30% of the altered
proteins physically interacted in described interferon mediated processes.
Comparison of the list of proteins that were identified as changed in the
proteomic analysis with data for the same proteins in the Interferome DB
indicated that ~35% of these proteins have not been reported to be IFN-gamma
responsive in a range of cell types. CONCLUSIONS: This data provides an in depth
analysis of the proteome of basal and IFN-gamma treated human mesenchymal stem
cells and it identifies a number of novel proteins that may contribute to the
immunoregulatory capacity if IFN-gamma licensed cells.
PMID- 28694745
TI - Model Averaging with AIC Weights for Hypothesis Testing of Hormesis at Low Doses.
AB - For many dose-response studies, large samples are not available. Particularly,
when the outcome of interest is binary rather than continuous, a large sample
size is required to provide evidence for hormesis at low doses. In a small or
moderate sample, we can gain statistical power by the use of a parametric model.
It is an efficient approach when it is correctly specified, but it can be
misleading otherwise. This research is motivated by the fact that data points at
high experimental doses have too much contribution in the hypothesis testing when
a parametric model is misspecified. In dose-response analyses, to account for
model uncertainty and to reduce the impact of model misspecification, averaging
multiple models have been widely discussed in the literature. In this article, we
propose to average semiparametric models when we test for hormesis at low doses.
We show the different characteristics of averaging parametric models and
averaging semiparametric models by simulation. We apply the proposed method to
real data, and we show that P values from averaged semiparametric models are more
credible than P values from averaged parametric methods. When the true dose
response relationship does not follow a parametric assumption, the proposed
method can be an alternative robust approach.
PMID- 28694744
TI - Protective Effects of Chrysin Against Drugs and Toxic Agents.
AB - ISSUES: Polyphenolic compounds, especially flavonoids, are known as the most
common chemical class of phytochemicals, which possess a multiple range of health
promoting effects. Flavonoids are ubiquitous in nature. They are also present in
food, providing an essential link between diet and prevention of several
diseases. APPROACH: Chrysin (CH), a natural flavonoid, was commonly found in
propolis and honey and traditionally used in herbal medicine. A growing body of
scientific evidence has shown that CH possesses protective effects against toxic
agents in various animal tissues, including brain, heart, liver, kidney, and
lung. KEY FINDINGS: This study found that CH may be effective in disease
management induced by toxic agents. However, due to the lack of information on
human, further studies are needed to determine the efficacy of CH as an antidote
agent in human. CONCLUSION: The present article aimed to critically review the
available literature data regarding the protective effects of CH against toxic
agent-induced toxicities as well as its possible mechanisms.
PMID- 28694746
TI - Forecasting Occurrences of Activities.
AB - While activity recognition has been shown to be valuable for pervasive computing
applications, less work has focused on techniques for forecasting the future
occurrence of activities. We present an activity forecasting method to predict
the time that will elapse until a target activity occurs. This method generates
an activity forecast using a regression tree classifier and offers an advantage
over sequence prediction methods in that it can predict expected time until an
activity occurs. We evaluate this algorithm on real-world smart home datasets and
provide evidence that our proposed approach is most effective at predicting
activity timings.
PMID- 28694747
TI - Evaluation of central and peripheral effects of doxepin on acetic acid-induced
colitis in rat and the involved mechanisms.
AB - Anti-colitis effect of antidepressants has been demonstrated recently. Doxepin, a
tricyclic antidepressant drug (TCA), with potent H1, H2, alpha1 adrenergic and
muscarinic receptor blocking effects could be a good candidate for investigation
for its anti-colitis activity. Moreover high prevalence of depression in patients
who suffer from IBD (inflammatory bowel disease), defends this idea that adjuvant
therapy with an antidepressant drug which has anti-inflammatory effect, may exert
favorable effects in the control of the disease. In this study colitis was
induced by acetic acid instillation into rat's colon. Doxepin was injected by
intraperitoneal (10, 20, 40 mg/kg, twice daily, i.p.) or intracerebroventricular
(50 and 100 microgram/rat, i.c.v.) routes to separate the mechanisms are
absolutely exerted centrally or mediated both centrally and peripherally prior to
induction of colitis. Dexamethasone (2 mg/kg/day, i.p.) was used as reference
drug. All the treatments continued for three successive days. The effectiveness
of drug was evaluated by determination of cytokines (TNFalpha, IL6 and IL1beta)
and myeloperoxidase (MPO) activity as well as macroscopic scores and
histopathological parameters. Doxepin after i.p. administration was effective to
reduce colitis severity through reduction in the macroscopic and microscopic
colonic parameters, MPO activity and cytokines levels. Intracerebroventricular
administration of the drug in contrast, did not show any significant protective
effect suggesting no important central mechanisms for anti-colitis activity of
doxepin. Doxepin as an ancient antidepressive drug has anti-colitis and anti
inflammatory properties which are mainly exerted peripherally so it could be
introduced as a good candidate for depressed people who suffered from IBD
disorders.
PMID- 28694748
TI - Protective effects of Scutellaria baicalensis Georgi against hydrogen peroxide
induced DNA damage and apoptosis in HaCaT human skin keratinocytes.
AB - Oxidative stress due to excessive accumulation of reactive oxygen species (ROS)
is one of the risk factors for the development of several chronic diseases. In
this study, we investigated the protective effects of Scutellaria baicalensis
rhizome ethanol extract (SBRE) against oxidative stress-induced cellular damage
and elucidated the underlying mechanisms in the HaCaT human skin keratinocyte
cell line. Our results revealed that treatment with SBRE prior to hydrogen
peroxide (H2O2) exposure significantly increased viability of HaCaT cells. SBRE
also effectively attenuated H2O2-induced comet tail formation and inhibited the
H2O2-induced phosphorylation levels of the histone gammaH2AX, as well as the
number of apoptotic bodies and Annexin V-positive cells. In addition, SBRE
exhibited scavenging activity against intracellular ROS generation and restored
the mitochondrial membrane potential loss by H2O2. Moreover, H2O2 enhanced the
cleavage of caspase-3 and degradation of poly (ADP-ribose)-polymerase, a typical
substrate protein of activated caspase-3, as well as DNA fragmentation; however,
these events were almost totally reversed by pretreatment with SBRE. Furthermore,
SBRE increased the levels of heme oxygenase-1 (HO-1), which is a potent
antioxidant enzyme, associated with the induction of nuclear factor-erythroid 2
related factor 2 (Nrf2). According to our data, SBRE is able to protect HaCaT
cells from H2O2-induced DNA damage and apoptosis through blocking cellular damage
related to oxidative stress through a mechanism that would affect ROS elimination
and activating the Nrf2/HO-1 signaling pathway.
PMID- 28694749
TI - Variability of antioxidant and biological activities of Rhus tripartitum related
to phenolic compounds.
AB - Rhus species are known in traditional medicine for their therapeutic virtue and
their extracts showed numerous important properties including antimalarial,
antimicrobial, antiviral, and hypoglycemic and anticonvulsant activities. Rhus
tripartitum (Ucria) is a medicinal plant widely used in Tunisia folk medicine
against chronic diarrhea and gastric ulcer. This study was designed to examine in
vitro and ex vivo antioxidant, anti-inflammatory and anticancer activities of
four extracts of Rhus tripartitum root cortex with increasing solvent polarity
(hexane, dichloromethane, methanol and water). HPLC was used to identify and
quantify phenolic compounds in Rhus extract. Water extract showed the highest
antioxidant activity using oxygen radical absorbance capacity (ORAC method) with
8.95 +/- 0.47 umol Trolox/mg and a cell based-assay with 0.28 +/- 0.12 umol
Trolox/mg as compared to the other fractions. Moreover, methanol extract
displayed the strongest anti-cancer activity against human lung carcinoma (A-549)
and colon adenocarcinoma cell lines (DLD-1) with an IC50 value of 60.69 +/- 2.58
and 39.83 +/- 4.56 ug/ml (resazurin test) and 44.52 +/- 5.96 and 55.65 +/- 6.00
ug/ml (hoechst test), respectively. Besides, the highest anti-inflammatory
activity, inhibiting nitric oxide (NO) release, was exhibited by dichloromethane
extract with 31.5 % at 160 ug/ml in lipopolysaccharide (LPS)-stimulated RAW 264.7
macrophages. The HPLC analysis showed that catechol and kaempferol were the major
phenolics. These data suggest the richness of all fractions of Ucria root on
interesting bioactive molecules with different polarity and confirm the known
traditional therapeutics virtues of this species for the treatment of dysentery,
diarrhea and gastric ulcer.
PMID- 28694750
TI - In vitro and in vivo anticancer studies of 2'-hydroxy chalcone derivatives
exhibit apoptosis in colon cancer cells by HDAC inhibition and cell cycle arrest.
AB - Considering the therapeutic values of bioflavonoids in colon cancer treatment,
six 2'-hydroxy chalcones (C1-C6) were synthesized, characterized and screened for
in vitro cytotoxicity on human colon carcinoma (HCT116) and African green monkey
kidney epithelial cells (Vero). Only C5 showed selective cytotoxicity against
HCT116 cells. Other potent cytotoxic compounds were C1, C2 and C3. Further
screening included enzyme inhibition studies on histone deacetylase (HDAC) enzyme
where C1 showed lowest IC50 value (105.03 uM). Based on cytotoxicity data C1, C2
and C3 were selected for further in vitro mechanistic studies, namely apoptotic
studies (Acridine orange/Ethidium bromide (AO/EB) and Annexin V), cell cycle
analysis using propidium iodide (PI) stain and in vivo anticancer efficacy in 1,2
dimethyl hydrazine (DMH) induced colorectal carcinoma in Wistar rats. The
compounds induced apoptosis in more than 30 % cells in AO/EB and Annexin V
staining. They also showed cell cycle arrest in G2/M phase with PI staining. They
showed a significant reduction in aberrant crypt foci formation and
adenocarcinoma count along with a significant (p<0.05) reduction in TNF-alpha
levels as compared to DMH control at 100 mg/kg dose. Thus, it can be concluded
that the synthesized 2'-hydroxychalcones were effective against colon
adenocarcinoma in in vitro and in vivo studies.
PMID- 28694751
TI - The role of magnesium sulfate in the intensive care unit.
AB - Magnesium (Mg) has been developed as a drug with various clinical uses. Mg is a
key cation in physiological processes, and the homeostasis of this cation is
crucial for the normal function of body organs. Magnesium sulfate (MgSO4) is a
mineral pharmaceutical preparation of magnesium that is used as a neuroprotective
agent. One rationale for the frequent use of MgSO4 in critical care is the high
incidence of hypomagnesaemia in intensive care unit (ICU) patients. Correction of
hypomagnesaemia along with the neuroprotective properties of MgSO4 has generated
a wide application for MgSO4 in ICU.
PMID- 28694752
TI - Ischemic preconditioning modulates ROS to confer protection in liver ischemia and
reperfusion.
AB - Ischemia reperfusion (IR) injury is a significant cause of morbidity and
mortality in liver transplantation. When oxygen is reintroduced to the liver
graft it initiates a cascade of molecular reactions leading to the release of
reactive oxygen species (ROS) and pro-inflammatory cytokines. These soluble
mediators propagate a sterile immune response to cause significant tissue damage.
Ischemic preconditioning (IPC) is one method that reduces hepatocellular injury
by altering the immune response and inhibiting the production of ROS. Studies
quantifying the effects of IPC in humans have demonstrated an improved liver
enzyme panel in patients receiving grafts pretreated with IPC as compared to
patients receiving the standard of care. In our review, we explore current
literature in the field in order to describe the mechanism through which IPC
regulates the production of ROS and improves IR injury.
PMID- 28694753
TI - Correlation of the plasma sphingoid base profile with results from oral glucose
tolerance tests in gestational diabetes mellitus.
AB - Oral glucose tolerance test (OGTT) is usually insufficient to accurately predict
the risk for type 2 diabetes mellitus (T2DM), it is therefore necessary to
identify an additional biomarker that would most likely improve the accuracy of
OGTT. The current OGTT was performed in 53 volunteers after ingestion of 75 g
glucose in 250 ml water to each volunteer. Similarly the sphingoid base profile
of these volunteers was explored using liquid-chromatography linked with mass
spectrometer (LC-MS) and correlated with the different time-points glucose values
of OGTT as well as with total area under the curve (tAUC), incremental area under
the curve (iAUC), and positive incremental area under the curve (pAUC). The
findings showed that 1-deoxysphinganine (1-deoxySA) was significantly positively
correlated with the 1-hour, 2-hour, and 3-hour plasma glucose level as well as
with total, incremental, and positive incremental AUC while 1-deoxysphingosine (1
deoxySO) was correlated only with 1-hour, 2-hour glucose levels and tAUC of OGTT.
The C18SAdiene was negatively correlated with all-time points glucose values and
AUCs followed by negative correlation of C18SO, C16SO and C17SO with 2-hour
glucose and tAUC of OGTT. The ratios of 1-deoxySA and 1-deoxySO with respect to
C18SAdiene have shown significant correlation with 2-hour and AUCs. These ratios
were higher in subjects with gestational diabetes in comparison with normal
subjects. These findings underlined that 1-deoxysphingolipids (1-deoxySLs) and
their ratios with C18SAdiene could be significantly correlated with the glucose
load of OGTT and might be used as predictive biomarkers along with OGTT for the
risk assessment of diabetes.
PMID- 28694754
TI - Using curcumin to prevent structural and behavioral changes of medial prefrontal
cortex induced by sleep deprivation in rats.
AB - Sleep Deprivation (SD) is known to result in a range of neurological consequences
in chronically-afflicted subjects. Curcumin, a natural substance, has
neuroprotective properties. This study aimed to evaluate the effects of curcumin
on the medial Prefrontal Cortex (mPFC) of SD rats. Male rats were arbitrarily
assigned to nine groups, including control, curcumin (100 mg/kg/day), olive oil,
SD, SD+curcumin, SD+olive oil, grid, grid+curcumin, and grid+olive oil groups. SD
was induced by a multiplatform box containing water. After a period of 21 days,
the learning and memory of the rats were tested in an eight-arm radial maze.
Afterwards, their brains were evaluated using stereological methods. Concomitant
treatment of curcumin during SD caused fewer errors during evaluation of the
working and reference memory errors in the acquisition and retention phases. The
overall volume of the mPFC, Infralimbic Cortex (ILC), Prelimbic Cortex (PLC),
Anterior Cingulate Cortex (ACC) and the total number of neurons and glial cells
reduced by 20 %-40 % on average in the SD animals in comparison to the control
group. This indicated atrophic changes and cell loss in these areas (p < 0.01).
The dendrites' length and the number of spines per dendrite also reduced by 35 %
55 % in the SD rats compared to the ones in the control group (p < 0.01). Yet,
treatment of the SD animals with curcumin prevented the atrophic changes of the
mPFC, cell loss, and dendritic changes (p < 0.05). SD induced structural changes
in the mPFC and memory impairment in the rats. However, curcumin could protect
their PFC.
PMID- 28694755
TI - Anti-inflammatory activity of hydrosols from Tetragonia tetragonoides in LPS
induced RAW 264.7 cells.
AB - The present study was performed to investigate the anti-inflammatory activity of
Tetragonia tetragonoides hydrosols (TTH) and its underlying mechanism in
lipopolysaccharide (LPS)-induced RAW 264.7 cells. Gas chromatography (GC) coupled
with mass spectrometry and retention index calculations showed that TTH were
mainly composed of tetratetracontane (29.5 %), nonacosane (27.6 %), and oleamide
(17.1 %). TTH significantly decreased the production of nitric oxide (NO),
prostaglandin E2 (PGE2), interleukin (IL)-6, and IL-1beta in LPS-stimulated RAW
264.7 cells. Consistent with these observations, TTH treatment decreased the
protein expression levels of inducible NO synthase (iNOS) and cyclooxygenase-2
(COX-2). The molecular mechanism of its anti-inflammatory activity was found to
be associated with inhibition of nuclear factor-kappa B (NF-kappaB)
phosphorylation and nuclear translocation of NF-kappaB 65. Furthermore, TTH
markedly suppressed the LPS-induced phosphorylation of mitogen-activated protein
kinases (MAPKs). Taken together, these data indicate that TTH exerts an anti
inflammatory activity by inhibiting the NF-kappaB and MAPK signaling pathways in
LPS-stimulated RAW 264.7 cells.
PMID- 28694756
TI - Electro-pharmacological profiles of two brain mitoplast anion channels:
Inferences from single channel recording.
AB - We have characterized the conduction and blocking properties of two different
chloride channels from brain mitochondrial inner membranes after incorporation
into planar lipid bilayers. Our experiments revealed the existence of channels
with a mean conductance of 158 +/- 7 and 301 +/- 8 pS in asymmetrical 200 mM
cis/50 mM trans KCl solutions. We determined that the channels were ten times
more permeable for Cl- than for K+, calculated from the reversal potential using
the Goldman-Hodgkin-Katz equation. The channels were bell-shaped voltage
dependent, with maximum open probability 0.9 at +/- 20 mV. Two mitochondrial
chloride channels were blocked after the addition of 10 uM DIDS. In addition, 158
pS chloride channel was blocked by 300 nM NPPB, acidic pH and 2.5 mM ATP, whereas
the 301 pS chloride channel was blocked by 600 uM NPPB but not by acidic pH or
ATP. Gating and conducting behaviors of these channels were unaffected by Ca2+.
These results demonstrate that the 158 pS anion channel present in brain
mitochondrial inner membrane, is probably identical to IMAC and 301 pS Cl channel
displays different properties than those classically described for mitochondrial
anion channels.
PMID- 28694757
TI - Neuroprotective effect of Azadirachta indica standardized extract in partial
sciatic nerve injury in rats: Evidence from anti-inflammatory, antioxidant and
anti-apoptotic studies.
AB - Chronic neuropathic pain is a common and widely recognized pain syndrome for
patients and difficult to manage for physicians. Azadirachta indica (AI)
possesses analgesic, anti-inflammatory, and antioxidant properties. To evaluate
the neuroprotective effect of AI standardized extract in an animal model of
peripheral neuropathy induced by partial sciatic nerve ligation (PSNL). PSNL was
induced in male Wistar rats (180-200 g) with tight ligation of the nerve. Rats
received treatment with either vehicle i.e. distilled water (PSNL control),
Pyridoxine (100 mg/kg, p.o.) or AI (100, 200 and 400 mg/kg, p.o.) for 28 days.
Various behavioral parameters, biochemical, molecular and histological parameters
were evaluated. PSNL resulted in a significant decrease (p < 0.05) in allodynia,
hyperalgesia, motor coordination and motor nerve conduction velocity (MNCV)
whereas chronic treatment with AI (200 and 400 mg/kg) significantly attenuated (p
< 0.05) these behavioral changes. Enhanced activity of oxidative-nitrosative
stress, inflammatory mediators (TNF-alpha, IL-1beta, and NF-kappaB) as well as
mRNA expression of Bax, Caspase-3, and iNOs were significantly attenuated (p <
0.05) by AI treatment. It also significantly increased (p < 0.05) peripheral
blood oxygen content and Bcl-2 mRNA expression. The flow cytometric analysis
revealed that AI (200 and 400 mg/kg) treatment significantly attenuated neural
apoptosis and reactive oxygen species levels. PSNL induced histological
aberrations were also decreased by AI treatment. Azadirachta indica exerts its
neuroprotection against PSNL induced neuropathic pain via inhibition of oxidative
nitrosative stress, the release of pro-inflammatory cytokines and apoptosis to
improve MNCV (graphical abstract, Figure 1(Fig. 1)).
PMID- 28694758
TI - Safety assessment and antioxidant activity of Lantana montevidensis leaves:
Contribution to its phytochemical and pharmacological activity.
AB - Lantana camara, the widely studied species, and L. montevidensis, the less
studied species of the genus Lantana are both used in traditional medicine for
the same purpose (anti-asthma, anti-ulcer, anti-tumor, etc). However, little is
known about the toxicity of L. montevidensis and there is limited information on
its chemical constituents. Here, we investigated for the first time the
genotoxicity and cytotoxicity of the ethanolic (EtOH) and aqueous extracts from
the leaves of Lantana montevidensis in human leukocytes, as well as their
possible interaction with human erythrocyte membranes in vitro. The antioxidant
activities of both extracts were also investigated in chemical and biological
models. Treatment of leukocytes with EtOH or aqueous extracts (1-480 ug/mL) did
not affect DNA damage index, but promoted cytotoxicity at higher concentrations
(240-480 ug/mL). Both extracts did not modify the osmotic fragility of human
erythrocytes. The extracts scavenged DPPH radical and prevented Fe2+-induced
lipid peroxidation in rat's brain and liver homogenates, and this was likely not
attributed to Fe (II) chelation. The HPLC analysis of the extracts showed
different amounts of polyphenolic compounds (isoquercitrin, gallic acid,
catechin, ellagic acid, apigenin, kaempferol, caffeic acid, rutin, quercitrin,
quercetin, chlorogenic acid, luteolin) that may have contributed to these
effects. These results supported information on the functional use of L.
montevidensis in folk medicine.
PMID- 28694759
TI - Using curcumin to prevent structural impairments of testicles in rats induced by
sodium metabisulfite.
AB - Sodium metabisulfite (Na-MBS) is a disinfectant and preservative agent. Some
organ including testicle would be in danger in the case of Na-MBS consumption.
Curcumin (CUR) is the constituent of turmeric with protective properties. The
effect of CUR on testicles in rats exposed to Na-MBS evaluated using
stereological methods. Sprague-Dawley rats were divided into eight groups. The
rats in groups I to VIII received the following respectively: distilled water,
CUR (100 mg/kg/day), low (0.7 mg/kg/day: acceptable daily intake), intermediate
(7 mg/ kg/day), and high (70 mg/kg/day) doses of Na-MBS, and low, intermediate,
and high doses of Na-MBS plus CUR. After 7 weeks, the testicles were analyzed.
The volume of seminiferous tubule, tubular epithelium and tubule length reduced
(25-40 %) on average in the rats that received intermediate and high doses of Na
MBS, while the connective tissue volume increased (15-20 %) in both groups
(P<0.01). Besides, 19-36 % and 41-57 % of the cells (spermatogonia types A and B,
spermatids, Sertoli and Leydig) were lost in the rats that received intermediate
and high doses of Na-MBS respectively in comparison to the control groups.
Nonetheless, all the above-mentioned alterations ameliorated drastically in the
rats that received Na-MBS plus CUR compared to those exposed to Na-MBS without
CUR therapy (P<0.01). The acceptable daily intake of Na-MBS for 7 weeks did not
affect on testicular parameters. CUR (100 mg/kg/day) could prevent structural
impairments of testicles in the rats induced by Na-MBS (7 and 70 mg/kg/day).
PMID- 28694760
TI - Genotoxic and cytotoxic potential of whole plant extracts of Kalanchoe laciniata
by Ames and MTT assay.
AB - Lack of data on safety of herbal medicines have endangered human health and life.
The present study evaluated the genotoxic and mutagenic effect of Kalanchoe
laciniata to access the safety and usefulness of the medicinal plant. Aqua
methanolic and n-hexane extracts of K. laciniata were evaluated for the genotoxic
potential using Ames assay and cytotoxicity was evaluated using MTT assay. Ames
assay was conducted using two strains of Salmonella typhimurium TA-100 and TA-102
whereas MTT assay was performed on baby hamster kidney cell line BHK-21. Aqua
methanolic extract of K.laciniata exhibited significant mutagenicity when exposed
to TA-102 strain with a mutagenic index of 50.66 and 54.74 at maximum dose 150
mg/plate. The extract was also mutagenic to TA-100 strain but to a lesser extent.
M.I of n-hexane extract was 12.15 and 15.51 for TA-100 and TA-102 respectively. n
hexane extract was mutagenic but little difference was observed between results
of two strains. Both extracts were found to be cytotoxic with an IC50 of 321.9
and 638.5 ug/mL for aqua-methanolic and n-hexane extracts respectively. On the
basis of results it was concluded that aqua-methanolic and n-hexane extracts of
K.laciniata possess mutagenic and cytotoxic potential. It is suggested to explore
the plant further to evaluate its safety in rodents and other species.
PMID- 28694761
TI - Recent studies on resveratrol and its biological and pharmacological activity.
PMID- 28694762
TI - Clinical significance of NCOA5 gene rs2903908 polymorphism in Behcet's disease.
AB - Behcet's disease (BD) is an autoimmune multisystemic disease. The precise
etiology of BD is not fully understood; however, it is thought that interactions
between genetic and environmental factors play an essential role in its
pathogenesis. The nuclear receptor coactivator-5 (NCOA5) gene encodes a
coregulator for nuclear receptor subfamily 1 group D member 2 (NR1D2) and
estrogen receptor 1 and 2 (ESR1 and ESR2). Also, the NCOA5 gene insufficiency
leads to an elevated expression of IL-6, and increased levels of IL-6 were found
to be related to the pathogenesis of BD. In this study, we aimed to clarify the
impact of the NCOA5 rs2903908 polymorphism on susceptibility and clinical
findings of BD. This study included 671 participants (300 BD patients and 371
healthy controls). The analyses of NCOA5 rs2903908 polymorphism was performed by
using the TaqMan allelic discrimination assay. The frequency of TT genotype of
the NCOA5 rs2903908 polymorphism was found significantly higher in BD patients
compared to those in healthy controls (p=0.016, OR=1.46, 95 % CI=1.08-1.99).
Also, the frequencies of CT genotype was observed significantly higher in BD
patients with genital ulceration and uveitis than without genital ulceration and
uveitis (p=0.002 and p=0.005, respectively). The most significant association was
found between C allele frequencies of BD patients with and without uveitis
(p=0.0001). Our study represents for the first time that the NCOA5 rs2903908
polymorphism seemed to be linked to BD susceptibility and clinical findings.
PMID- 28694763
TI - MiR-429 suppresses the progression and metastasis of osteosarcoma by targeting
ZEB1.
AB - MiR-429 functions as a tumor suppressor and has been observed in multiple types
of cancer, but the effects and mechanisms of miR-429 in osteosarcoma are poorly
understood. This study is performed to evaluate the functions of miR-429 in the
progression of osteosarcoma. Firstly, the miR-429 expression in osteosarcoma
tissues and osteosarcoma cells was detected using real time PCR, and the
relationship between miR-429 expression and overall survival of osteosarcoma was
analyzed. Secondly, the effects of miR-429 on the migration, invasion,
proliferation and apoptosis of osteosarcoma cells were evaluated using transwell
assay, wound-healing assay, CCK-8 assay and flow cytometry, respectively.
Proteins related to epithelial-mesenchymal transition (EMT), E-cadherin,
Vimentin, N-cadherin and Snail, were also detected using Western blot. Finally,
the target gene of miR-429 in osteosarcoma was predicted and verified using dual
luciferase assay and the expression correlation between them was analyzed using
Pearson's correlation. MiR-429 was down-regulated in osteosarcoma tissues and
osteosarcoma cells; the expression level of miR-429 was associated with the
prognosis of osteosarcoma. High level of miR-429 in osteosarcoma cells
significantly suppressed the migration, invasion and proliferation of cells but
induced cells apoptosis. Furthermore, high level of miR-429 in osteosarcoma cells
obviously increased the expression of E-cadherin protein but decreased the
expression of Vimentin, N-Cadherin and Snail proteins. EMT inducer ZEB1 was the
target gene of miR-429 and the expression of ZEB1 was negatively related to the
miR-429 expression in osteosarcoma. In conclusion, miR-429 may functions as a
tumor suppressor and be down-regulated in osteosarcoma. MiR-429 may suppress the
progression and metastasis of osteosarcoma by down-regulating the ZEB1
expression.
PMID- 28694764
TI - 2-pyrazoline derivatives in neuropharmacology: Synthesis, ADME prediction,
molecular docking and in vivo biological evaluation.
AB - A novel series of 1,3,5-trisubstituted-2-pyrazoline derivatives (PFC-1 to PFC-16)
were synthesized in a three step reaction using conventional and microwave
assisted green chemistry approach. The synthesized derivatives were characterized
and their chemical structures were established by various physicochemical methods
such as IR, Mass, 1H-NMR, 13C-NMR and elemental analysis. The synthesized
compounds were tested for their neuropharmacological potential. The compounds
exhibited significant antidepressant and anti-anxiety activities against various
behavioral in vivo models. Compounds PFC-3 and PFC-12 were found to be the most
active derivatives in the series. The 2-pyrazoline analogs, having 2
hydroxyphenyl and anthracen-9-yl substitution at 3rd position while 4
benzyloxyphenyl and 4-methylphenyl substitution at 5th position, were decisive in
eliciting good antidepressant and anxiolytic properties, respectively. The
docking experiments revealed that the synthesized derivatives were potential
inhibitors of MAO-A protein, which plays a central role in managing depression
and anxiety disorders. The most potent derivatives were found to be involved in
some key interactions with Tyr407, Tyr444, Phe352 and Ala68 amino acid residues
at the binding site of MAO-A protein. All the synthesized derivatives
successfully passed the pharmacokinetic barriers of absorption, distribution,
metabolism and elimination as predicted using in silico techniques without
showing any substantial indication of acute and neurotoxicity. This was further
confirmed in the laboratory by performing acute toxicity studies as per OECD
guidelines.
PMID- 28694765
TI - Cellular uptake and anti-tumor activity of gemcitabine conjugated with new
amphiphilic cell penetrating peptides.
AB - Gemcitabine (Gem) is used as a single agent or in combination with other
anticancer agents to treat many types of solid tumors. However, it has many
limitations such as a short plasma half-life, dose-limiting toxicities and drug
resistance. Cell-penetrating peptides (CPPs) are short peptides which may deliver
a large variety of cargo molecules into the cancerous cells. The current study
was designed to evaluate the antiproliferative activity of gemcitabine chemically
conjugated to CPPs. The peptides were synthesized using solid phase synthesis
procedure. The uptake efficiency of CPPs into cells was examined by flow
cytometry and fluorescent microscopy. The synthesized peptides were chemically
conjugated to Gem and the in vitro cytotoxicity of conjugates was tested by MTT
assay on A594 cell line. According to the obtained results, cellular uptake was
increased with increasing the concentration of CPPs. On the other hand the
coupling of Gem with peptides containing block sequence of arginine (R5W3R4) and
some alternating sequences (i.e. [RW]6 and [RW]3) exhibited improved antitumor
activity of the drug. The findings in this study support the advantages of using
cell-penetrating peptides for improving intracellular delivery of Gem into tumor
as well as its activity.
PMID- 28694766
TI - Flavoenzyme-mediated reduction reactions and antitumor activity of nitrogen
containing tetracyclic ortho-quinone compounds and their nitrated derivatives.
AB - Nitrogen-based tetracyclic ortho-quinones (naphtho[1'2':4.5]imidazo[1,2
a]pyridine-5,6-diones, NPDOs) and their nitro-substituted derivatives (nitro
(P)NPDOs) were obtained by condensation of substituted 2,3-dichloro-1,4
naphthoquinones with 2-amino-pyridine and -pyrimidine and nitration at an
elevated temperature. The structural features of the compounds as well as their
global and regional electrophilic potency were characterized by means of DFT
computation. The compounds were highly reactive substrates of single- and two
electron (hydride) - transferring P-450R (CPR; EC 1.6.2.4) and NQO-1 (DTD; EC
1.6.99.2), respectively, concomitantly producing reactive oxygen species. Their
catalytic efficiency defined in terms of the apparent second-order rate constant
(kcat/KM (Q)) values in P-450R- and NQO-1-mediated reactions varied in the range
of 3-6 * 107 M-1 s-1 and 1.6-7.4 * 108 M-1 s-1, respectively. The cytotoxic
activities of the compounds on tumor cell lines followed the concentration
dependent manner exhibiting relatively high cytotoxic potency against breast
cancer MCF-7, with CL50 values of 0.08-2.02 uM L-1 and lower potency against lung
cancer A-549 (CL50 = 0.28-7.66 uM L-1). 3-nitro-pyrimidino-NPDO quinone was the
most active compound against MCF-7 with CL50 of 0.08 +/- 0.01 uM L-1 (0.02 ug mL
1)) which was followed by 3-nitro-NPDO with CL50 of 0.12 +/- 0.03 uM L-1 (0.035
ug mL-1)) and 0.28 +/- 0.08 uM L-1 (0.08 ug mL-1) on A-549 and MCF-7 cells,
respectively, while 1- and 4-nitro-quinoidals produced the least cytotoxic
effects. Tumor cells quantified by AO/EB staining showed that the cell death
induced by the compounds occurs primarily through apoptosis.
PMID- 28694767
TI - Development of a new rutin nanoemulsion and its application on prostate carcinoma
PC3 cell line.
AB - Biological effects of rutin bioactive are limited due to its poor oral
bioavailability and its degradation in aqueous environments. For the purpose of
bioenhancement, different nanoemulsion systems of rutin were developed by aqueous
titration method using water as dispersion media. The nanoemulsion systems were
characterized for surface morphology, droplet size, polydispersity index, zeta
potential, in vitro release profile and the formulations were optimized. The
anticancer potential of optimized nanoemulsion was evaluated by cells viability
(MTT) assay, nuclear condensation, and ROS activity using human prostate cancer
(PC3) cell line. On the basis of cell viability data the inhibitory concentration
(IC50) value for optimized nanoemulsion formulation on PC3 cancer cells was found
to be 11.8 MUM. Fluorescent microscopic analysis and intracellular ROS generation
demonstrated significant ROS induction that might lead to triggering the
apoptosis pathway. In conclusion, developed nanoemulsion displayed significant
efficacy against prostate carcinoma cells.
PMID- 28694768
TI - The androgen receptor plays different roles in macrophage-induced proliferation
in prostate stromal cells between transitional and peripheral zones of benign
prostatic hypertrophy.
AB - Macrophages play a critical role in the process of excessive stromal
proliferation of benign prostatic hyperplasia (BPH). In our previous study, we
used a BPH mouse model to elucidate a potential mechanism whereby macrophage
infiltration promotes stromal cell proliferation in the prostate via the androgen
receptor (AR)/inflammatory cytokine CCL3-dependent pathway. In our present study,
we used the co-culture system of human macrophages and various prostatic zone
stromal cells to further demonstrate that infiltrating macrophages promote
prostatic stromal cell proliferation through stromal AR-dependent pathways, and
we show that the stroma of TZ and PZ respond to macrophages differently because
of differences in stromal AR signaling; this could possibly be one of the key
pathways for stromal expansion during BPH development and progression. We
hypothesize that AR and different downstream inflammatory mediators between TZ
and PZ could serve as potential targets for the future design of therapeutic
agents for BPH and our results provide significant insights into the search for
targeted therapeutic approaches to battle BPH.
PMID- 28694770
TI - Spatial Cues Provided by Sound Improve Postural Stabilization: Evidence of a
Spatial Auditory Map?
AB - It has long been suggested that sound plays a role in the postural control
process. Few studies however have explored sound and posture interactions. The
present paper focuses on the specific impact of audition on posture, seeking to
determine the attributes of sound that may be useful for postural purposes. We
investigated the postural sway of young, healthy blindfolded subjects in two
experiments involving different static auditory environments. In the first
experiment, we compared effect on sway in a simple environment built from three
static sound sources in two different rooms: a normal vs. an anechoic room. In
the second experiment, the same auditory environment was enriched in various
ways, including the ambisonics synthesis of a immersive environment, and subjects
stood on two different surfaces: a foam vs. a normal surface. The results of both
experiments suggest that the spatial cues provided by sound can be used to
improve postural stability. The richer the auditory environment, the better this
stabilization. We interpret these results by invoking the "spatial hearing map"
theory: listeners build their own mental representation of their surrounding
environment, which provides them with spatial landmarks that help them to better
stabilize.
PMID- 28694769
TI - Hypothalamic Integration of Metabolic, Endocrine, and Circadian Signals in Fish:
Involvement in the Control of Food Intake.
AB - The regulation of food intake in fish is a complex process carried out through
several different mechanisms in the central nervous system (CNS) with
hypothalamus being the main regulatory center. As in mammals, a complex
hypothalamic circuit including two populations of neurons: one co-expressing
neuropeptide Y (NPY) and Agouti-related peptide (AgRP) and the second one
population co-expressing pro-opiomelanocortin (POMC) and cocaine- and amphetamine
regulated transcript (CART) is involved in the integration of information
relating to food intake control. The production and release of these peptides
control food intake, and the production results from the integration of
information of different nature such as levels of nutrients and hormones as well
as circadian signals. The present review summarizes the knowledge and recent
findings about the presence and functioning of these mechanisms in fish and their
differences vs. the known mammalian model.
PMID- 28694771
TI - Nupr1 Modulates Methamphetamine-Induced Dopaminergic Neuronal Apoptosis and
Autophagy through CHOP-Trib3-Mediated Endoplasmic Reticulum Stress Signaling
Pathway.
AB - Methamphetamine (METH) is an illegal and widely abused psychoactive stimulant.
METH exposure causes detrimental effects on multiple organ systems, primarily the
nervous system, especially dopaminergic pathways, in both laboratory animals and
humans. In this study, we hypothesized that Nuclear protein 1 (Nupr1/com1/p8) is
involved in METH-induced neuronal apoptosis and autophagy through endoplasmic
reticulum (ER) stress signaling pathway. To test this hypothesis, we measured the
expression levels of Nupr1, ER stress protein markers CHOP and Trib3, apoptosis
related protein markers cleaved-caspase3 and PARP, as well as autophagy-related
protein markers LC3 and Beclin-1 in brain tissues of adult male Sprague-Dawley
(SD) rats, rat primary cultured neurons and the rat adrenal pheochromocytoma
cells (PC12 cells) after METH exposure. We also determined the effects of METH
exposure on the expression of these proteins after silencing Nupr1, CHOP, or
Trib3 expression with synthetic small hairpin RNA (shRNA) or siRNA in vitro, and
after silencing Nupr1 in the striatum of rats by injecting lentivirus containing
shRNA sequence targeting Nupr1 gene to rat striatum. The results showed that METH
exposure increased Nupr1 expression that was accompanied with increased
expression of ER stress protein markers CHOP and Trib3, and also led to apoptosis
and autophagy in rat primary neurons and in PC12 cells after 24 h exposure (3.0
mM), and in the prefrontal cortex and striatum of rats after repeated
intraperitoneal injections (15 mg/kg * 8 injections at 12 h intervals). Silencing
of Nupr1 expression partly reduced METH-induced apoptosis and autophagy in vitro
and in vivo. These results suggest that Nupr1 plays an essential role in METH
caused neuronal apoptosis and autophagy at relatively higher doses and may be a
potential therapeutic target in high-dose METH-induced neurotoxicity.
PMID- 28694772
TI - Connexin-Dependent Neuroglial Networking as a New Therapeutic Target.
AB - Astrocytes and neurons dynamically interact during physiological processes, and
it is now widely accepted that they are both organized in plastic and tightly
regulated networks. Astrocytes are connected through connexin-based gap junction
channels, with brain region specificities, and those networks modulate neuronal
activities, such as those involved in sleep-wake cycle, cognitive, or sensory
functions. Additionally, astrocyte domains have been involved in neurogenesis and
neuronal differentiation during development; they participate in the "tripartite
synapse" with both pre-synaptic and post-synaptic neurons by tuning down or up
neuronal activities through the control of neuronal synaptic strength. Connexin
based hemichannels are also involved in those regulations of neuronal activities,
however, this feature will not be considered in the present review. Furthermore,
neuronal processes, transmitting electrical signals to chemical synapses,
stringently control astroglial connexin expression, and channel functions. Long
range energy trafficking toward neurons through connexin-coupled astrocytes and
plasticity of those networks are hence largely dependent on neuronal activity.
Such reciprocal interactions between neurons and astrocyte networks involve
neurotransmitters, cytokines, endogenous lipids, and peptides released by neurons
but also other brain cell types, including microglial and endothelial cells. Over
the past 10 years, knowledge about neuroglial interactions has widened and now
includes effects of CNS-targeting drugs such as antidepressants, antipsychotics,
psychostimulants, or sedatives drugs as potential modulators of connexin function
and thus astrocyte networking activity. In physiological situations, neuroglial
networking is consequently resulting from a two-way interaction between astrocyte
gap junction-mediated networks and those made by neurons. As both cell types are
modulated by CNS drugs we postulate that neuroglial networking may emerge as new
therapeutic targets in neurological and psychiatric disorders.
PMID- 28694773
TI - Loud Noise Exposure Produces DNA, Neurotransmitter and Morphological Damage
within Specific Brain Areas.
AB - Exposure to loud noise is a major environmental threat to public health. Loud
noise exposure, apart from affecting the inner ear, is deleterious for
cardiovascular, endocrine and nervous systems and it is associated with
neuropsychiatric disorders. In this study we investigated DNA, neurotransmitters
and immune-histochemical alterations induced by exposure to loud noise in three
major brain areas (cerebellum, hippocampus, striatum) of Wistar rats. Rats were
exposed to loud noise (100 dBA) for 12 h. The effects of noise on DNA integrity
in all three brain areas were evaluated by using Comet assay. In parallel
studies, brain monoamine levels and morphology of nigrostriatal pathways,
hippocampus and cerebellum were analyzed at different time intervals (24 h and 7
days) after noise exposure. Loud noise produced a sudden increase in DNA damage
in all the brain areas under investigation. Monoamine levels detected at 7 days
following exposure were differently affected depending on the specific brain
area. Namely, striatal but not hippocampal dopamine (DA) significantly decreased,
whereas hippocampal and cerebellar noradrenaline (NA) was significantly reduced.
This is in line with pathological findings within striatum and hippocampus
consisting of a decrease in striatal tyrosine hydroxylase (TH) combined with
increased Bax and glial fibrillary acidic protein (GFAP). Loud noise exposure
lasting 12 h causes immediate DNA, and long-lasting neurotransmitter and immune
histochemical alterations within specific brain areas of the rat. These
alterations may suggest an anatomical and functional link to explain the
neurobiology of diseases which prevail in human subjects exposed to environmental
noise.
PMID- 28694774
TI - Memory Performance for Everyday Motivational and Neutral Objects Is Dissociable
from Attention.
AB - Episodic memory is typically better for items coupled with monetary reward or
punishment during encoding. It is yet unclear whether memory is also enhanced for
everyday objects with appetitive or aversive values learned through a lifetime of
experience, and to what extent episodic memory enhancement for motivational and
neutral items is attributable to attention. In a first experiment, we
investigated attention to everyday motivational objects using eye-tracking during
free-viewing and subsequently tested episodic memory using a remember/know
procedure. Attention was directed more to aversive stimuli, as evidenced by
longer viewing durations, whereas recollection was higher for both appetitive and
aversive objects. In the second experiment, we manipulated the visual contrast of
neutral objects through changes of contrast to further dissociate attention and
memory encoding. While objects presented with high visual contrast were looked at
longer, recollection was best for objects presented in unmodified, medium
contrast. Generalized logistic mixed models on recollection performance showed
that attention as measured by eye movements did not enhance subsequent memory,
while motivational value (Experiment 1) and visual contrast (Experiment 2) had
quadratic effects in opposite directions. Our findings suggest that an
enhancement of incidental memory encoding for appetitive items can occur without
an increase in attention and, vice versa, that enhanced attention towards salient
neutral objects is not necessarily associated with memory improvement. Together,
our results provide evidence for a double dissociation of attention and memory
effects under certain conditions.
PMID- 28694775
TI - Yoga, Meditation and Mind-Body Health: Increased BDNF, Cortisol Awakening
Response, and Altered Inflammatory Marker Expression after a 3-Month Yoga and
Meditation Retreat.
AB - Thirty-eight individuals (mean age: 34.8 years old) participating in a 3-month
yoga and meditation retreat were assessed before and after the intervention for
psychometric measures, brain derived neurotrophic factor (BDNF), circadian
salivary cortisol levels, and pro- and anti-inflammatory cytokines. Participation
in the retreat was found to be associated with decreases in self-reported anxiety
and depression as well as increases in mindfulness. As hypothesized, increases in
the plasma levels of BDNF and increases in the magnitude of the cortisol
awakening response (CAR) were also observed. The normalized change in BDNF levels
was inversely correlated with BSI-18 anxiety scores at both the pre-retreat (r =
0.40, p < 0.05) and post-retreat (r = 0.52, p < 0.005) such that those with
greater anxiety scores tended to exhibit smaller pre- to post-retreat increases
in plasma BDNF levels. In line with a hypothesized decrease in inflammatory
processes resulting from the yoga and meditation practices, we found that the
plasma level of the anti-inflammatory cytokine Interleukin-10 was increased and
the pro-inflammatory cytokine Interleukin-12 was reduced after the retreat.
Contrary to our initial hypotheses, plasma levels of other pro-inflammatory
cytokines, including Interferon Gamma (IFN-gamma), Tumor Necrosis Factor (TNF
alpha), Interleukin-1beta (IL-1beta), Interleukin-6 (IL-6), and Interleukin-8 (IL
8) were increased after the retreat. Given evidence from previous studies of the
positive effects of meditative practices on mental fitness, autonomic homeostasis
and inflammatory status, we hypothesize that these findings are related to the
meditative practices throughout the retreat; however, some of the observed
changes may also be related to other aspects of the retreat such as physical
exercise-related components of the yoga practice and diet. We hypothesize that
the patterns of change observed here reflect mind-body integration and well
being. The increased BDNF levels observed is a potential mediator between
meditative practices and brain health, the increased CAR is likely a reflection
of increased dynamic physiological arousal, and the relationship of the dual
enhancement of pro- and anti-inflammatory cytokine changes to healthy immunologic
functioning is discussed.
PMID- 28694776
TI - Visualization, Interaction and Tractometry: Dealing with Millions of Streamlines
from Diffusion MRI Tractography.
AB - Recently proposed tractography and connectomics approaches often require a very
large number of streamlines, in the order of millions. Generating, storing and
interacting with these datasets is currently quite difficult, since they require
a lot of space in memory and processing time. Compression is a common approach to
reduce data size. Recently such an approach has been proposed consisting in
removing collinear points in the streamlines. Removing points from streamlines
results in files that cannot be robustly post-processed and interacted with
existing tools, which are for the most part point-based. The aim of this work is
to improve visualization, interaction and tractometry algorithms to robustly
handle compressed tractography datasets. Our proposed improvements are threefold:
(i) An efficient loading procedure to improve visualization (reduce memory usage
up to 95% for a 0.2 mm step size); (ii) interaction techniques robust to
compressed tractograms; (iii) tractometry techniques robust to compressed
tractograms to eliminate biased in tract-based statistics. The present work
demonstrates the need of correctly handling compressed streamlines to avoid
biases in future tractometry and connectomics studies.
PMID- 28694779
TI - Embryo and Developmental Toxicity of Cefazolin Sodium Impurities in Zebrafish.
AB - Cefazolin sodium is an essential drug that is widely used in clinical therapy for
certain infective diseases caused by bacteria. As drug impurities are considered
to be one of the most important causes of drug safety issues, we studied
embryotoxicity, cardiotoxicity, and neurotoxicity of nine cefazolin sodium
impurities in zebrafish embryo and larvae for the objective control of impurity
profiling. LC-MS/MS was employed to analyze the compound absorbance in vivo, and
the structure-toxicity relationship was approached. Our results suggested that
the structure of MMTD (2-mercapto-5-methyl-1, 3, 4-thiadiazole) is the main toxic
functional group for embryo deformities; the 7-ACA (7-aminocephalosporanic acid)
structure mainly affects motor nerve function; and both the MMTD and 7-ACA
structures are responsible for cardiac effects. Impurity G (7-ACA) presented with
the strongest toxicity; impurity A was most extensively absorbed to embryo and
larvae; and impurity F (MMTD) exhibited the strongest apparent toxic effect;
Therefore, impurities F and G should be monitored from the cefazolin sodium
preparations.
PMID- 28694778
TI - North African Medicinal Plants Traditionally Used in Cancer Therapy.
AB - Background: Cancer is a major cause of mortality worldwide with increasing
numbers by the years. In North Africa, the number of cancer patients is alarming.
Also shocking is that a huge number of cancer patients only have access to
traditional medicines due to several factors, e.g., economic difficulties. In
fact, medicinal plants are widely used for the treatment of several pathologies,
including cancer. Truthfully, herbalists and botanists in North African countries
prescribe several plants for cancer treatment. Despite the popularity and the
potential of medicinal plants for the treatment of cancer, scientific evidence on
their anticancer effects are still scarce for most of the described plants.
Objective: Bearing in mind the lack of comprehensive and systematic studies, the
aim of this review is to give an overview of studies, namely ethnobotanical
surveys and experimental evidence of anticancer effects regarding medicinal
plants used in North Africa for cancer therapy. Method: The research was
conducted on several popular search engines including PubMed, Science Direct,
Scopus and Web of Science. The research focused primarily on English written
papers published between the years 2000 and 2016. Results: This review on plants
traditionally used by herbalists in North Africa highlights that Morocco and
Algeria are the countries with most surveys on the use of medicinal plants in
folk medicine. Among the plethora of plants used, Nigella sativa and Trigonella
foenum-graecum are the most referred ones by herbalists for the treatment of
cancer. Moreover, a plethora of scientific evidence qualifies them as candidates
for further drug development. Furthermore, we report on the underlying cellular
and molecular mechanisms. Conclusion: Overall, this review highlights the
therapeutic potential of some medicinal plants as anticancer agents. The North
African flora offers a rich source of medicinal plants for a wide array of
diseases, including cancer. The elucidation of their modes of action represents
an indispensable condition for the rational development of new drugs for cancer
treatment. Furthermore, testing the anticancer activity in vivo and in clinical
trials are warranted to explore the full therapeutic potential of North African
plants for cancer therapy.
PMID- 28694777
TI - Pharmacological Properties and Molecular Mechanisms of Thymol: Prospects for Its
Therapeutic Potential and Pharmaceutical Development.
AB - Thymol, chemically known as 2-isopropyl-5-methylphenol is a colorless crystalline
monoterpene phenol. It is one of the most important dietary constituents in thyme
species. For centuries, it has been used in traditional medicine and has been
shown to possess various pharmacological properties including antioxidant, free
radical scavenging, anti-inflammatory, analgesic, antispasmodic, antibacterial,
antifungal, antiseptic and antitumor activities. The present article presents a
detailed review of the scientific literature which reveals the pharmacological
properties of thymol and its multiple therapeutic actions against various
cardiovascular, neurological, rheumatological, gastrointestinal, metabolic and
malignant diseases at both biochemical and molecular levels. The noteworthy
effects of thymol are largely attributed to its anti-inflammatory (via inhibiting
recruitment of cytokines and chemokines), antioxidant (via scavenging of free
radicals, enhancing the endogenous enzymatic and non-enzymatic antioxidants and
chelation of metal ions), antihyperlipidemic (via increasing the levels of high
density lipoprotein cholesterol and decreasing the levels of low density
lipoprotein cholesterol and low density lipoprotein cholesterol in the
circulation and membrane stabilization) (via maintaining ionic homeostasis)
effects. This review presents an overview of the current in vitro and in vivo
data supporting thymol's therapeutic activity and the challenges concerning its
use for prevention and its therapeutic value as a dietary supplement or as a
pharmacological agent or as an adjuvant along with current therapeutic agents for
the treatment of various diseases. It is one of the potential candidates of
natural origin that has shown promising therapeutic potential, pharmacological
properties and molecular mechanisms as well as pharmacokinetic properties for the
pharmaceutical development of thymol.
PMID- 28694780
TI - The Effect of Pungent and Tingling Compounds from Piper nigrum L. on Background
K+ Currents.
AB - Black peppercorns (Piper nigrum L.) elicit a pungent and tingling oral
impression. Their pungency is partially explained by the agonist activity of some
of their active principles, especially piperine, on TRP channels. However, we
recently showed that piperine, as well as other pungent compounds, also possess a
marked effect on two-pore domain (KCNK, K2P) K+ channels. Members of this family
play a key role in maintaining the resting membrane potential of excitable cells.
Interestingly, tingling compounds have been shown to induce neuronal excitation
by inhibiting KCNK channels. We addressed the question of whether it was
plausible that KCNK channels could constitute a physiologically relevant target
for the sensory active compounds present in black peppercorns. Because previous
studies have demonstrated that mouse trigeminal neurons respond to several
pungent compounds, to which humans are also sensitive, we used a primary culture
of mouse trigeminal neurons to investigate whether the effect of piperine on
these cell types could also be mediated by KCNK channels. We observed that even
in the presence of classical TRP-antagonists, piperine was still able to activate
a fraction of trigeminal neurons. Furthermore, our results showed that piperine
is capable of inducing neuronal depolarization by a mechanism that does not
require extracellular Na+ or Ca2+. This depolarization was mediated by the
inhibition of a background K+ conductance, most likely corresponding to the KCNK
channels of the TASK subfamily. We then performed a screening with 12 other
pungent and/or tingling chemosensates isolated from black peppercorns. These
compounds were evaluated on Xenopus laevis oocytes expressing the human
orthologues of KCNK3, KNCK9 and KCNK18, which we previously showed to be
inhibited by piperine. Remarkably, almost all of the isolated chemosensates
inhibited the basal activity of hKCNK3, with 1-(octadeca-2E,4E,13/12Z
trienoyl)pyrrolidine acting as one of the most potent natural blockers for hKCNK3
found to date. Our results suggest that KCNK channels, especially KCNK3, are
likely to play a complementary role to TRP channels in the complex orosensory
impression elicited by black peppercorns, while they also help to expand the
pharmacological knowledge of KCNK channels.
PMID- 28694782
TI - Evaluation of Abdominal Fetal Electrocardiography in Early Intrauterine Growth
Restriction.
AB - Objectives: This descriptive study was performed to evaluate the capability of a
non-invasive transabdominal electrocardiographic system to extract clear fetal
electrocardiographic (FECG) measurements from intrauterine growth restricted
(IUGR) fetuses and to assess whether abdominal FECG parameters can be developed
as markers for evaluating the fetal cardiac status in IUGR. Methods:
Transabdominal FECG was attempted in 20 controls and 15 IUGR singleton
pregnancies at 20+0-33+6 weeks gestation. Standard ECG parameters were compared
between the study groups and evaluated for their correlation. Accuracy for the
prediction of IUGR by cut off values of the different FECG parameters was also
determined. Results: Clear P-QRST complexes were recognized in all cases. In the
IUGR fetuses, the QT and QTc intervals were significantly prolonged (p = 0.017
and p = 0.002, respectively). There was no correlation between ECG parameters and
Doppler or other indices to predict IUGR. The generation of cut off values for
detecting IUGR showed increasing sensitivities but decreasing specificities with
the prolongation of ECG parameters. Conclusion: The study of fetal
electrocardiophysiology is now feasible through a non-invasive transabdominal
route. This study confirms the potential of FECG as a clinical screening tool to
aid diagnosis and management of fetuses after key limitations are addressed. In
the case of IUGR, both QT and QTc intervals were significantly prolonged and thus
validate earlier study findings where both these parameters were found to be
markers of diastolic dysfunction. This research is a useful prelude to a test of
accuracy and Receiver Operating Characteristics (ROC) study.
PMID- 28694781
TI - Amelogenesis Imperfecta; Genes, Proteins, and Pathways.
AB - Amelogenesis imperfecta (AI) is the name given to a heterogeneous group of
conditions characterized by inherited developmental enamel defects. AI enamel is
abnormally thin, soft, fragile, pitted and/or badly discolored, with poor
function and aesthetics, causing patients problems such as early tooth loss,
severe embarrassment, eating difficulties, and pain. It was first described
separately from diseases of dentine nearly 80 years ago, but the underlying
genetic and mechanistic basis of the condition is only now coming to light.
Mutations in the gene AMELX, encoding an extracellular matrix protein secreted by
ameloblasts during enamel formation, were first identified as a cause of AI in
1991. Since then, mutations in at least eighteen genes have been shown to cause
AI presenting in isolation of other health problems, with many more implicated in
syndromic AI. Some of the encoded proteins have well documented roles in
amelogenesis, acting as enamel matrix proteins or the proteases that degrade
them, cell adhesion molecules or regulators of calcium homeostasis. However, for
others, function is less clear and further research is needed to understand the
pathways and processes essential for the development of healthy enamel. Here, we
review the genes and mutations underlying AI presenting in isolation of other
health problems, the proteins they encode and knowledge of their roles in
amelogenesis, combining evidence from human phenotypes, inheritance patterns,
mouse models, and in vitro studies. An LOVD resource
(http://dna2.leeds.ac.uk/LOVD/) containing all published gene mutations for AI
presenting in isolation of other health problems is described. We use this
resource to identify trends in the genes and mutations reported to cause AI in
the 270 families for which molecular diagnoses have been reported by 23rd May
2017. Finally we discuss the potential value of the translation of AI genetics to
clinical care with improved patient pathways and speculate on the possibility of
novel treatments and prevention strategies for AI.
PMID- 28694783
TI - MPA Modulates Tight Junctions' Permeability via Midkine/PI3K Pathway in Caco-2
Cells: A Possible Mechanism of Leak-Flux Diarrhea in Organ Transplanted Patients.
AB - Mycophenolic acid (MPA) is prescribed to prevent allograft rejection in organ
transplanted patients. However, its use is sporadically linked to leak flux
diarrhea and other gastrointestinal (GI) disturbances in around 75% of patients
through yet unknown mechanisms. Recently, we identified Midkine as a modulator of
tight junctions (TJs) permeability in MPA treated Caco-2 monolayer. In the
present study, we investigated the possible involvement of Midkine dependent PI3K
pathway in alteration of TJs under MPA treatment. Caco-2 cells were grown as
monolayer to develop TJs and were treated for 72 h with DMSO (control) or MPA in
presence and absence of Midkine inhibitor (iMDK) or PI3K inhibitors (LY/AMG).
Caco-2 monolayer integrity was assessed by transepithelial electrical resistance
(TEER) and FITC-dextran assays. Our functional assays showed that PI3K inhibitors
(LY/AMG) can significantly inhibit the compromised TJs integrity of MPA-treated
Caco-2 cells monolayer. Chromatin immunoprecipitation analyses showed a
significant epigenetic activation of Midkine, PI3K, Cdx-2, and Cldn-2 genes and
epigenetic repression of Cldn-1 gene after MPA treatment. The MPA-induced
epigenetic alterations were further confirmed by mRNA and protein expression
analysis. Collectively, our data shows that PI3K pathway as the downstream target
of Midkine which in turn modulates p38MAPK and pAKT signaling to alter TJs
permeability in Caco-2 cell monolayers treated with MPA. These results highlight
the possible use of either Midkine or PI3K inhibitors as therapeutic agents to
prevent MPA induced GI disturbances.
PMID- 28694784
TI - 4D Flow Analysis of BAV-Related Fluid-Dynamic Alterations: Evidences of Wall
Shear Stress Alterations in Absence of Clinically-Relevant Aortic Anatomical
Remodeling.
AB - Bicuspid aortic valve (BAV) is the most common congenital cardiac disease and is
a foremost risk factor for aortopathies. Despite the genetic basis of BAV and of
the associated aortopathies, BAV-related alterations in aortic fluid-dynamics,
and particularly in wall shear stresses (WSSs), likely play a role in the
progression of aortopathy, and may contribute to its pathogenesis. To test
whether WSS may trigger aortopathy, in this study we used 4D Flow sequences of
phase-contrast cardiac magnetic resonance imaging (CMR) to quantitatively compare
the in vivo fluid dynamics in the thoracic aorta of two groups of subjects: (i)
five prospectively enrolled young patients with normo-functional BAV and with no
aortic dilation and (ii) ten age-matched healthy volunteers. Through the semi
automated processing of 4D Flow data, the aortic bulk flow at peak systole was
quantified, and WSSs acting on the endothelium of the ascending aorta were
characterized throughout the systolic phase in terms of magnitude and time
dependency through a method recently developed by our group. Variables computed
for each BAV patient were compared vs. the corresponding distribution of values
obtained for healthy controls. In BAV patients, ascending aorta diameter was
measured on cine-CMR images at baseline and at 3-year follow-up. As compared to
controls, normo-functional BAV patients were characterized by minor bulk flow
disturbances at peak systole. However, they were characterized by evident
alterations of WSS distribution and peak values in the ascending aorta. In
particular, in four BAV patients, who were characterized by right-left leaflet
fusion, WSS peak values exceeded by 27-46% the 90th percentile of the
distribution obtained for healthy volunteers. Only in the BAV patient with right
non-coronary leaflet fusion the same threshold was exceeded by 132%. Also,
evident alterations in the time-dependency of WSS magnitude and direction were
observed. Despite, these fluid-dynamic alterations, no clinically relevant
anatomical remodeling was observed in the BAV patients at 3-year follow-up. In
light of previous evidence from the literature, our results suggest that WSS
alterations may precede the onset of aortopathy and may contribute to its
triggering, but WSS-driven anatomical remodeling, if any, is a very slow process.
PMID- 28694785
TI - What About Their Performance Do Free Jazz Improvisers Agree Upon? A Case Study.
AB - When musicians improvise freely together-not following any sort of script,
predetermined harmonic structure, or "referent"-to what extent do they understand
what they are doing in the same way as each other? And to what extent is their
understanding privileged relative to outside listeners with similar levels of
performing experience in free improvisation? In this exploratory case study, a
saxophonist and a pianist of international renown who knew each other's work but
who had never performed together before were recorded while improvising freely
for 40 min. Immediately afterwards the performers were interviewed separately
about the just-completed improvisation, first from memory and then while
listening to two 5 min excerpts of the recording in order to prompt specific and
detailed commentary. Two commenting listeners from the same performance community
(a saxophonist and drummer) listened to, and were interviewed about, these
excerpts. Some months later, all four participants rated the extent to which they
endorsed 302 statements that had been extracted from the four interviews and
anonymized. The findings demonstrate that these free jazz improvisers
characterized the improvisation quite differently, selecting different moments to
comment about and with little overlap in the content of their characterizations.
The performers were not more likely to endorse statements by their performing
partner than by a commenting listener from the same performance community, and
their patterns of agreement with each other (endorsing or dissenting with
statements) across multiple ratings-their interrater reliability as measured with
Cohen's kappa-was only moderate, and not consistently higher than their agreement
with the commenting listeners. These performers were more likely to endorse
statements about performers' thoughts and actions than statements about the music
itself, and more likely to endorse evaluatively positive than negative
statements. But these kinds of statements were polarizing; the performers were
more likely to agree with each other in their ratings of statements about the
music itself and negative statements. As in Schober and Spiro (2014), the
evidence supports a view that fully shared understanding is not needed for joint
improvisation by professional musicians in this genre and that performing
partners can agree with an outside listener more than with each other.
PMID- 28694786
TI - Joint Rhythmic Movement Increases 4-Year-Old Children's Prosocial Sharing and
Fairness Toward Peers.
AB - The allocation of resources to a peer partner is a prosocial act that is of
fundamental importance. Joint rhythmic movement, such as occurs during musical
interaction, can induce positive social experiences, which may play a role in
developing and enhancing young children's prosocial skills. Here, we investigated
whether joint rhythmic movement, free of musical context, increases 4-year-olds'
sharing and sense of fairness in a resource allocation task involving peers. We
developed a precise procedure for administering joint synchronous experience,
joint asynchronous experience, and a baseline control involving no treatment.
Then we tested how participants allocated resources between self and peer. We
found an increase in the generous allocation of resources to peers following both
synchronous and asynchronous movement compared to no treatment. At a more
theoretical level, this result is considered in relation to previous work testing
other aspects of child prosociality, for example, peer cooperation, which can be
distinguished from judgments of fairness in resource allocation tasks. We draw a
conceptual distinction between two types of prosocial behavior: resource
allocation (an other-directed individual behavior) and cooperation (a goal
directed collaborative endeavor). Our results highlight how rhythmic
interactions, which are prominent in joint musical engagements and synchronized
activity, influence prosocial behavior between preschool peers.
PMID- 28694787
TI - What Makes You Go Faster?: The Effect of Reward on Speeded Action under Risk.
AB - Evaluating the potential reward and risk associated with a choice of action plays
an important role in everyday decision making. However, the details behind how
reward and risk affect the decisions for actions remain unclear. The present
study investigates the influence of reward and risk on a decision to make a
speeded motor response. One hundred and ten college students performed a Speed
Rewarded Go-NoGo task during which they were rewarded proportionally based on the
speed and accuracy of their response. On each trial, the magnitude of potential
reward and the probability of a forthcoming Go signal (Go-probability) were
presented prior to the Go or NoGo signal. Personality traits, such as risk taking
and impulsive tendencies, were measured to determine their contribution in
explaining individual differences in task performance. The results showed that
larger amount of rewards can motivate people to respond faster, and this effect
was modulated by the assessed risk, suggesting that decisions for actions are
based on a systematic trade-off between rewards and risks. Moreover, when the
assessed risk was high, individuals with greater risk taking and impulsive
tendencies did not adequately adjust their behavior across different reward
levels. These findings shed light on the mechanistic understanding of the effect
of reward and risk on decisions for a speeded action.
PMID- 28694788
TI - The Relationship between the Physical Activity Environment, Nature Relatedness,
Anxiety, and the Psychological Well-being Benefits of Regular Exercisers.
AB - Research from a variety of scientific fields suggests that physical activity in
nature and feelings of connection to nature enhance psychological health and well
being. This study investigated the psychological health and well-being impact of
the physical activity environment for those already undertaking the recommended
weekly amount of physical activity. This topic is important for the design of
health and well-being environments and interventions involving physical activity.
Participants (N = 262) aged 18-71 years (M = 34.5, SD = 13.1) who met the UK
physical activity guidelines completed the Nature Relatedness Scale, the trait
section of the State Trait Inventory for Cognitive and Somatic Anxiety and the
Psychological Well-Being Scale. Analysis via Multivariate ANOVA indicated that
participants who engaged in outdoor physical activity reported significantly
lower somatic anxiety levels and higher Nature Relatedness experience (NRexp).
Significant results were not evident for wellbeing. Hierarchical regressions
revealed that the psychological well-being facet of autonomy, NRexp, and outdoor
physical activity predicted lower somatic anxiety, whereas indoor physical
activity predicted higher somatic anxiety. Results indicate that somatic anxiety
is lower for outdoor physical activity participation, and that outdoor activity,
in conjunction with autonomy and NRexp, predicts lower anxiety levels. The
findings extend previous work by demonstrating the impact of the physical
activity environment on anxiety levels, as well as the contribution of outdoor
physical activity and well-being facets to the previously established Nature
Relatedness-anxiety relationship.
PMID- 28694789
TI - History of Gestational Diabetes Mellitus in Relation to Cardiovascular Disease
and Cardiovascular Risk Factors in US Women.
AB - BACKGROUND: Findings from previous studies examining the association between
gestational diabetes mellitus (GDM) and subsequent risk of cardiovascular disease
(CVD) have been inconsistent and inconclusive. We aimed to examine the
associations of a previous history of GDM with risk of CVD and status of
cardiovascular risk factors in a nationwide population-based study in the United
States. METHODS: This study included 8,127 parous women aged 20 years or older in
the 2007-2014 cycles of the National Health and Nutrition Examination Survey in
the United States. The exposure was self-reported diagnostic history of GDM and
the outcomes were self-reported diagnostic history of CVD and measurements of
cardiovascular risk factors, including blood pressure and blood lipids.
Regression models with sample weights were used to examine the associations of
GDM with CVD and cardiovascular risk factors. RESULTS: Among women with a history
of both GDM and CVD, CVD was diagnosed on average 22.9 years after the diagnosis
of GDM. After adjustment for demographic, socioeconomic, and lifestyle factors, a
history of GDM was associated with 63% higher odds of CVD [odds ratio (OR) 1.63,
95% confidence interval (CI) 1.02, 2.62, p-value = 0.04]. Further adjustment for
body mass index (BMI) modestly attenuated the association (OR 1.52, 95% CI 0.95,
2.44, p-value = 0.08). A history of GDM was significantly associated with lower
serum level of HDL-cholesterol (adjusted beta-coefficient -3.33, 95% CI -5.17,
1.50, p-value <= 0.001), but not associated with total cholesterol, LDL
cholesterol, triglycerides, or systolic or diastolic blood pressure. Similarly,
the association between a history of GDM and HDL cholesterol was attenuated after
additional adjustment for BMI (adjusted beta-coefficient -1.68, 95% CI -3.38,
0.03, p-value = 0.54). CONCLUSION: Women with a previous history of GDM have
significantly higher risk for developing CVD and lower serum level of HDL
cholesterol, compared to women without a history of GDM. The associations may be
explained, at least partly, by BMI.
PMID- 28694790
TI - Does Valproic Acid Have Potential in the Treatment of Diabetes Mellitus?
PMID- 28694791
TI - No Clear Differences between Organic or Conventional Pig Farms in the Genetic
Diversity or Virulence of Campylobacter coli Isolates.
AB - To evaluate the impact of pig farm management on the genetic diversity and on the
virulence of Campylobacter coli, we characterized isolates from 19 organic pig
farms (62 isolates) and from 24 conventional pig farms (58 isolates). The 120 C.
coli isolates were typed using pulsed field gel electrophoresis (PFGE) and
multilocus sequence typing (MLST) and the presence of nine virulence genes was
screened using real-time PCR. The capacity of adhesion and invasion of 61
isolates (32 from organic and 29 from conventional farms) were then tested on
human intestinal Caco-2 cells. A total of 59 PFGE types and of 50 sequence types
(STs) were identified. Twelve PFGE types and nine STs, accounting for 34 and
41.6% of the isolates, respectively, were common between the two production
systems with ST854 dominating (18.3% of the isolates). Twenty-nine PFGE types and
25 STs were only found in isolates from organic farms, and 18 PFGE types and 16
STs from conventional farms. No significant differences were found in diversity
despite the differences in rearing systems, except at the locus level for the
glnA, gltA, and uncA genes. All isolates, regardless of their origin, carried the
ceuE, iam, ciaB, and flaA genes and more than 95% of the isolates carried the
cadF and cdtABC genes. No significant differences were found in pathogenicity
between the two farming systems. The pathogenicity of the C. coli isolates was
low compared to C. jejuni control strains tested. The plasmid gene virb11 was
detected in only 13 isolates from organic farms; these isolates showed greater
invasion capacity than those without this gene. Our study indicates that pig farm
management does not significantly affect the diversity and the virulence of
Campylobacter coli isolated from pigs. The common genotypes between conventional
and organic farms may indicate that some genotypes are adapted to pigs.
PMID- 28694792
TI - Context Is Everything: Harmonization of Critical Food Microbiology Descriptors
and Metadata for Improved Food Safety and Surveillance.
AB - Globalization of food networks increases opportunities for the spread of
foodborne pathogens beyond borders and jurisdictions. High resolution whole
genome sequencing (WGS) subtyping of pathogens promises to vastly improve our
ability to track and control foodborne disease, but to do so it must be combined
with epidemiological, clinical, laboratory and other health care data (called
"contextual data") to be meaningfully interpreted for regulatory and health
interventions, outbreak investigation, and risk assessment. However, current
multi-jurisdictional pathogen surveillance and investigation efforts are
complicated by time-consuming data re-entry, curation and integration of
contextual information owing to a lack of interoperable standards and
inconsistent reporting. A solution to these challenges is the use of 'ontologies'
- hierarchies of well-defined and standardized vocabularies interconnected by
logical relationships. Terms are specified by universal IDs enabling integration
into highly regulated areas and multi-sector sharing (e.g., food and water
microbiology with the veterinary sector). Institution-specific terms can be
mapped to a given standard at different levels of granularity, maximizing
comparability of contextual information according to jurisdictional policies. Fit
for-purpose ontologies provide contextual information with the auditability
required for food safety laboratory accreditation. Our research efforts include
the development of a Genomic Epidemiology Ontology (GenEpiO), and Food Ontology
(FoodOn) that harmonize important laboratory, clinical and epidemiological data
fields, as well as existing food resources. These efforts are supported by a
global consortium of researchers and stakeholders worldwide. Since foodborne
diseases do not respect international borders, uptake of such vocabularies will
be crucial for multi-jurisdictional interpretation of WGS results and data
sharing.
PMID- 28694793
TI - Comparative Genomic Characterization of the Highly Persistent and Potentially
Virulent Cronobacter sakazakii ST83, CC65 Strain H322 and Other ST83 Strains.
AB - Cronobacter (C.) sakazakii is an opportunistic pathogen and has been associated
with serious infections with high mortality rates predominantly in pre-term, low
birth weight and/or immune compromised neonates and infants. Infections have been
epidemiologically linked to consumption of intrinsically and extrinsically
contaminated lots of reconstituted powdered infant formula (PIF), thus
contamination of such products is a challenging task for the PIF producing
industry. We present the draft genome of C. sakazakii H322, a highly persistent
sequence type (ST) 83, clonal complex (CC) 65, serotype O:7 strain obtained from
a batch of non-released contaminated PIF product. The presence of this strain in
the production environment was traced back more than 4 years. Whole genome
sequencing (WGS) of this strain together with four more ST83 strains (PIF
production environment-associated) confirmed a high degree of sequence homology
among four of the five strains. Phylogenetic analysis using microarray (MA) and
WGS data showed that the ST83 strains were highly phylogenetically related and MA
showed that between 5 and 38 genes differed from one another in these strains.
All strains possessed the pESA3-like virulence plasmid and one strain possessed a
pESA2-like plasmid. In addition, a pCS1-like plasmid was also found. In order to
assess the potential in vivo pathogenicity of the ST83 strains, each strain was
subjected to infection studies using the recently developed zebrafish embryo
model. Our results showed a high (90-100%) zebrafish mortality rate for all of
these strains, suggesting a high risk for infections and illness in neonates
potentially exposed to PIF contaminated with ST83 C. sakazakii strains. In
summary, virulent ST83, CC65, serotype CsakO:7 strains, though rarely found
intrinsically in PIF, can persist within a PIF manufacturing facility for years
and potentially pose significant quality assurance challenges to the PIF
manufacturing industry.
PMID- 28694794
TI - Antivirulent Properties of Underexplored Cinnamomum tamala Essential Oil and Its
Synergistic Effects with DNase against Pseudomonas aeruginosa Biofilms - An In
Vitro Study.
AB - Pseudomonas aeruginosa is a nosocomial pathogen colonizing patients with chronic
infectious diseases and has gained resistance to all the known broad spectrum
antibiotics available today. The present study showcases the antibiofilm
potential of an essential oil (EO) from an underexplored Cinnamomum species
namely, C. tamala, against P. aeruginosa biofilms. Furthermore, the synergistic
effects of the EO along with a commercially available DNase (DNaseI) and a DNase
(MBD) isolated from a marine bacterium were explored for its antibiofilm
activity. The results showed that the synergized action has maximum efficacy in
inhibiting young and preformed biofilms. The synergized effect of EO and DNaseI
showed 70% inhibition against matured biofilms of P. aeruginosa. The EO from C.
tamala also showed quorum sensing inhibitory potential as it could inhibit the
swarming motility behavior of P. aeruginosa. The synergistic action of EO and
DNases offers a novel alternate therapeutic strategy for combating P. aeruginosa
biofilm associated infections.
PMID- 28694795
TI - Modulation of Host miRNAs Transcriptome in Lung and Spleen of Peste des Petits
Ruminants Virus Infected Sheep and Goats.
AB - Peste des petits ruminants (PPR) is one of the highly contagious viral disease,
characterized by fever, sore mouth, conjunctivitis, gastroenteritis, and
pneumonia, primarily affecting sheep and goats. Reports suggested variable host
response in goats and sheep and this host response vis-a-vis the expression of
microRNAs (miRNAs) has not been investigated. Here, miRNAs were sequenced and
proteomics data were generated to identify the role of differentially expressed
miRNA (DEmiRNA) in PPR virus (PPRV) infected lung and spleen tissues of sheep and
goats. In lungs, 67 and 37 DEmiRNAs have been identified in goats and sheep,
respectively. Similarly, in spleen, 50 and 56 DEmiRNAs were identified in goats
and sheep, respectively. A total of 20 and 11 miRNAs were found to be common
differentially expressed in both the species in PPRV infected spleen and lung,
respectively. Six DEmiRNAs-miR-21-3p, miR-1246, miR-27a-5p, miR-760-3p, miR-320a,
and miR-363 were selected based on their role in viral infections, apoptosis, and
fold change. The target prediction analysis of these six selected DEmiRNAs from
the proteome data generated, revealed involvement of more number of genes in lung
and spleen of goats than in sheep. On gene ontology analysis of host target genes
these DEmiRNAs were found to regulate several immune response signaling pathways.
It was observed that the pathways viz. T cell receptor signaling, Rap1 signaling,
Toll-like receptor signaling, and B cell receptor signaling governed by DEmiRNAs
were more perturbed in goats than in sheep. The data suggests that PPRV-induced
miR-21-3p, miR-320a, and miR-363 might act cooperatively to enhance viral
pathogenesis in the lung and spleen of sheep by downregulating several immune
response genes. The study gives an important insight into the molecular
pathogenesis of PPR by identifying that the PPRV-Izatnagar/94 isolate elicits a
strong host response in goats than in sheep.
PMID- 28694796
TI - Evolutionary Diversification of Alanine Transaminases in Yeast: Catabolic
Specialization and Biosynthetic Redundancy.
AB - Gene duplication is one of the major evolutionary mechanisms providing raw
material for the generation of genes with new or modified functions. The yeast
Saccharomyces cerevisiae originated after an allopolyploidization event, which
involved mating between two different ancestral yeast species. ScALT1 and ScALT2
codify proteins with 65% identity, which were proposed to be paralogous alanine
transaminases. Further analysis of their physiological role showed that while
ScALT1 encodes an alanine transaminase which constitutes the main pathway for
alanine biosynthesis and the sole pathway for alanine catabolism, ScAlt2 does not
display alanine transaminase activity and is not involved in alanine metabolism.
Moreover, phylogenetic studies have suggested that ScALT1 and ScALT2 come from
each one of the two parental strains which gave rise to the ancestral hybrid. The
present work has been aimed to the understanding of the properties of the
ancestral type Lacchancea kluyveri LkALT1 and Kluyveromyces lactis KlALT1,
alanine transaminases in order to better understand the ScALT1 and ScALT2
evolutionary history. These ancestral -type species were chosen since they harbor
ALT1 genes, which are related to ScALT2. Presented results show that, although
LkALT1 and KlALT1 constitute ScALT1 orthologous genes, encoding alanine
transaminases, both yeasts display LkAlt1 and KlAlt1 independent alanine
transaminase activity and additional unidentified alanine biosynthetic and
catabolic pathway(s). Furthermore, phenotypic analysis of null mutants uncovered
the fact that KlAlt1 and LkAlt1 have an additional role, not related to alanine
metabolism but is necessary to achieve wild type growth rate. Our study shows
that the ancestral alanine transaminase function has been retained by the ScALT1
encoded enzyme, which has specialized its catabolic character, while losing the
alanine independent role observed in the ancestral type enzymes. The fact that
ScAlt2 conserves 64% identity with LkAlt1 and 66% with KlAlt1, suggests that
ScAlt2 diversified after the ancestral hybrid was formed. ScALT2 functional
diversification resulted in loss of both alanine transaminase activity and the
additional alanine-independent LkAlt1 function, since ScALT2 did not complement
the Lkalt1Delta phenotype. It can be concluded that LkALT1 and KlLALT1 functional
role as alanine transaminases was delegated to ScALT1, while ScALT2 lost this
role during diversification.
PMID- 28694797
TI - Genome Data Provides High Support for Generic Boundaries in Burkholderia Sensu
Lato.
AB - Although the taxonomy of Burkholderia has been extensively scrutinized,
significant uncertainty remains regarding the generic boundaries and composition
of this large and heterogeneous taxon. Here we used the amino acid and nucleotide
sequences of 106 conserved proteins from 92 species to infer robust maximum
likelihood phylogenies with which to investigate the generic structure of
Burkholderia sensu lato. These data unambiguously supported five distinct
lineages, of which four correspond to Burkholderia sensu stricto and the newly
introduced genera Paraburkholderia, Caballeronia, and Robbsia. The fifth lineage
was represented by P. rhizoxinica. Based on these findings, we propose 13 new
combinations for those species previously described as members of Burkholderia
but that form part of Caballeronia. These findings also suggest revision of the
taxonomic status of P. rhizoxinica as it is does not form part of any of the
genera currently recognized in Burkholderia sensu lato. From a phylogenetic point
of view, Burkholderia sensu stricto has a sister relationship with the
Caballeronia+Paraburkholderia clade. Also, the lineages represented by P.
rhizoxinica and R. andropogonis, respectively, emerged prior to the radiation of
the Burkholderia sensu stricto+Caballeronia+Paraburkholderia clade. Our findings
therefore constitute a solid framework, not only for supporting current and
future taxonomic decisions, but also for studying the evolution of this
assemblage of medically, industrially and agriculturally important species.
PMID- 28694798
TI - Dynamic Co-evolution and Interaction of Avian Leukosis Virus Genetic Variants and
Host Immune Responses.
AB - Subgroup J avian leukosis virus (ALV-J), a typical retrovirus, is characterized
of existence of a cloud of diverse variants and considerable genetic diversity.
Previous studies describing the evolutionary dynamics of ALV-J genetic variants
mainly focused on the early infection period or few randomly selected clones.
Here, we inoculated 30 specific-pathogen-free chickens with the same founder ALV
J stock of known genetic background. Six (three antibody positive and three
antibody negative) chickens were selected among 15 chickens with viremia. Viruses
were serially isolated in 36 weeks and then sequenced using MiSeq high-throughput
sequencing platform. This produced the largest ALV-J dataset to date, composed of
more than three million clean reads. Our results showed that host humoral
immunity could greatly enhance the genetic diversity of ALV-J genetic variants.
In particular, selection pressures promoted a dynamic proportional changes in ALV
J genetic variants frequency. Cross-neutralization experiment showed that along
with the change of the dominant variant, the antibody titers specific to
infectious clones corresponding to the most dominant variants in weeks 12 and 28
have also changed significantly in sera collected in weeks 16 and 32. In
contrast, no shift of dominant variant was observed in antibody-negative
chickens. Moreover, we identified a novel hypervariable region in the gp85 gene.
Our study reveals the interaction between ALV-J and the host, which could
facilitate the development of vaccines and antiviral drugs.
PMID- 28694799
TI - A Tiny RNA that Packs a Big Punch: The Critical Role of a Viral miR-155 Ortholog
in Lymphomagenesis in Marek's Disease.
AB - MicroRNAs (miRNAs) are small non-coding RNAs that have been identified in
animals, plants, and viruses. These small RNAs play important roles in post
transcriptional regulation of various cellular processes, including development,
differentiation, and all aspects of cancer biology. Rapid-onset T-cell lymphoma
of chickens, namely Marek's disease (MD), induced by Gallid alphaherpesvirus 2
(GaHV2), could provide an ideal natural animal model for herpesvirus-related
cancer research. GaHV2 encodes 26 mature miRNAs derived from 14 precursors
assembled in three distinct gene clusters in the viral genome. One of the most
highly expressed GaHV2 miRNAs, miR-M4-5p, shows high sequence similarity to the
cellular miR-155 and the miR-K12-11 encoded by Kaposi's sarcoma-associated
herpesvirus, particularly in the miRNA "seed region." As with miR-K12-11, miR-M4
5p shares a common set of host and viral target genes with miR-155, suggesting
that they may target the same regulatory cellular networks; however, differences
in regulatory function between miR-155 and miR-M4-5p may distinguish non-viral
and viral mediated tumorigenesis. In this review, we focus on the functions of
miR-M4-5p as the viral ortholog of miR-155 to explore how the virus mimics a host
pathway to benefit the viral life cycle and trigger virus-induced tumorigenesis.
PMID- 28694800
TI - Bacterial Survival under Extreme UV Radiation: A Comparative Proteomics Study of
Rhodobacter sp., Isolated from High Altitude Wetlands in Chile.
AB - Salar de Huasco, defined as a polyextreme environment, is a high altitude saline
wetland in the Chilean Altiplano (3800 m.a.s.l.), permanently exposed to the
highest solar radiation doses registered in the world. We present here the first
comparative proteomics study of a photoheterotrophic bacterium, Rhodobacter sp.,
isolated from this remote and hostile habitat. We developed an innovative
experimental approach using different sources of radiation (in situ sunlight and
UVB lamps), cut-off filters (Mylar, Lee filters) and a high-throughput, label
free quantitative proteomics method to comprehensively analyze the effect of
seven spectral bands on protein regulation. A hierarchical cluster analysis of 40
common proteins revealed that all conditions containing the most damaging UVB
radiation induced similar pattern of protein regulation compared with UVA and
visible light spectral bands. Moreover, it appeared that the cellular adaptation
of Rhodobacter sp. to osmotic stress encountered in the hypersaline environment
from which it was originally isolated, might further a higher resistance to
damaging UV radiation. Indeed, proteins involved in the synthesis and transport
of key osmoprotectants, such as glycine betaine and inositol, were found in very
high abundance under UV radiation compared to the dark control, suggesting the
function of osmolytes as efficient reactive oxygen scavengers. Our study also
revealed a RecA-independent response and a tightly regulated network of protein
quality control involving proteases and chaperones to selectively degrade
misfolded and/or damaged proteins.
PMID- 28694801
TI - The GATA-Type Transcription Factor Csm1 Regulates Conidiation and Secondary
Metabolism in Fusarium fujikuroi.
AB - GATA-type transcription factors (TFs) such as the nitrogen regulators AreA and
AreB, or the light-responsive TFs WC-1 and WC-2, play global roles in fungal
growth and development. The conserved GATA TF NsdD is known as an activator of
sexual development and key repressor of conidiation in Aspergillus nidulans, and
as light-regulated repressor of macroconidia formation in Botrytis cinerea. In
the present study, we functionally characterized the NsdD ortholog in Fusarium
fujikuroi, named Csm1. Deletion of this gene resulted in elevated microconidia
formation in the wild-type (WT) and restoration of conidiation in the non
sporulating velvet mutant Deltavel1 demonstrating that Csm1 also plays a role as
repressor of conidiation in F. fujikuroi. Furthermore, biosynthesis of the PKS
derived red pigments, bikaverin and fusarubins, is de-regulated under otherwise
repressing conditions. Cross-species complementation of the Deltacsm1 mutant with
the B. cinerea ortholog LTF1 led to full restoration of WT-like growth,
conidiation and pigment formation. In contrast, the F. fujikuroi CSM1 rescued
only the defects in growth, the tolerance to H2O2 and virulence, but did not
restore the light-dependent differentiation when expressed in the B. cinerea
Deltaltf1 mutant. Microarray analysis comparing the expression profiles of the F.
fujikuroi WT and the Deltacsm1 mutant under different nitrogen conditions
revealed a strong impact of this GATA TF on 19 of the 47 gene clusters in the
genome of F. fujikuroi. One of the up-regulated silent gene clusters is the one
containing the sesquiterpene cyclase-encoding key gene STC1. Heterologous
expression of STC1 in Escherichia coli enabled us to identify the product as the
volatile bioactive compound (-)-germacrene D.
PMID- 28694802
TI - The Response Regulator Slr1588 Regulates spsA But Is Not Crucial for Salt
Acclimation of Synechocystis sp. PCC 6803.
AB - Cyanobacterial sucrose biosynthesis is stimulated under salt stress, which could
be used for biotechnological sugar production. It has been shown that the
response regulator Slr1588 negatively regulates the spsA gene encoding sucrose
phosphate synthase and mutation of the slr1588 gene also affected the salt
tolerance of Synechocystis (Chen et al., 2014). The latter finding is contrary to
earlier observations (Hagemann et al., 1997b). Here, we observed that ectopic
expression of slr1588 did not restore the salt tolerance of the slr1588 mutant,
making the essential function of this response regulator for salt tolerance
questionable. Subsequent experiments showed that deletion of the entire coding
sequence of slr1588 compromised the expression of the downstream situated ggpP
gene, which encodes glucosylglycerol-phosphate phosphatase for synthesis of the
primary osmolyte glucosylglycerol. Mutation of slr1588 by deleting the N-terminal
part of this protein (Deltaslr1588-F976) did not affect ggpP expression,
glucosylglycerol accumulation as well as salt tolerance, while the mutation of
ggpP resulted in the previously reported salt-sensitive phenotype. In the
Deltaslr1588-F976 mutant spsA was up-regulated but sucrose content was lowered
due to increased invertase activity. Our results reveal that Slr1588 is acting as
a repressor for spsA as previously suggested but it is not crucial for the
overall salt acclimation of Synechocystis.
PMID- 28694803
TI - Comparative Genomics Identifies a Novel Conserved Protein, HpaT, in
Proteobacterial Type III Secretion Systems that Do Not Possess the Putative
Translocon Protein HrpF.
AB - Xanthomonas translucens is the causal agent of bacterial leaf streak, the most
common bacterial disease of wheat and barley. To cause disease, most xanthomonads
depend on a highly conserved type III secretion system, which translocates type
III effectors into host plant cells. Mutagenesis of the conserved type III
secretion gene hrcT confirmed that the X. translucens type III secretion system
is required to cause disease on the host plant barley and to trigger a non-host
hypersensitive response (HR) in pepper leaves. Type III effectors are delivered
to the host cell by a surface appendage, the Hrp pilus, and a translocon protein
complex that inserts into the plant cell plasma membrane. Homologs of the
Xanthomonas HrpF protein, including PopF from Ralstonia solanacearum and NolX
from rhizobia, are thought to act as a translocon protein. Comparative genomics
revealed that X. translucens strains harbor a noncanonical hrp gene cluster,
which rather shares features with type III secretion systems from Ralstonia
solanacearum, Paraburkholderia andropogonis, Collimonas fungivorans, and
Uliginosibacterium gangwonense than other Xanthomonas spp. Surprisingly, none of
these bacteria, except R. solanacearum, encode a homolog of the HrpF translocon.
Here, we aimed at identifying a candidate translocon from X. translucens.
Notably, genomes from strains that lacked hrpF/popF/nolX instead encode another
gene, called hpaT, adjacent to and co-regulated with the type III secretion
system gene cluster. An insertional mutant in the X. translucens hpaT gene, which
is the first gene of a two-gene operon, hpaT-hpaH, was non-pathogenic on barley
and did not cause the HR or programmed cell death in non-host pepper similar to
the hrcT mutant. The hpaT mutant phenotypes were partially complemented by either
hpaT or the downstream gene, hpaH, which has been described as a facilitator of
translocation in Xanthomonas oryzae. Interestingly, the hpaT mutant was also
complemented by the hrpF gene from Xanthomonas euvesicatoria. These findings
reveal that both HpaT and HpaH contribute to the injection of type III effectors
into plant cells.
PMID- 28694804
TI - CD169 Expressing Macrophage, a Key Subset in Mesenteric Lymph Nodes Promotes
Mucosal Inflammation in Dextran Sulfate Sodium-Induced Colitis.
AB - Inflammatory bowel disease (IBD) including Crohn's disease (CD) and ulcerative
colitis is a relapsing-remitting illness. Patients with long-standing extensive
colitis are easy to develop colorectal cancer (CRC). The increasing incidence of
IBD and a substantial increase in the risk of CRC make the necessity to pay more
attention on the regulation of inflammation especially by specific macrophages
subset. The present study reported that a key subset of sinus macrophage
expressing CD169 in mesenteric lymph nodes (mLNs) played an essential role in
promoting mucosal inflammation. The results revealed that the subset expressing
CD169 in mLNs increased significantly during the dextran sulfate sodium (DSS)
induced colitis. The colitic symptoms were alleviated in CD169-diphtheria toxin
receptor (DTR) mice at least partially due to the deletion of CD169+ macrophages
in mLNs. In addition, the levels of inflammatory cytokines as well as the
percentage of Th17 cells in mLNs from CD169-DTR mice were much lower than those
from WT mice with DSS-induced colitis. Further experiment in vitro demonstrated
that the supernatant from whole cells of mLNs or colon tissues could promote the
production of inflammatory factors by mLN cells or colon tissues from CD169-DTR
mice. These results could be explained by the cell sorting result that
CD11b+CD169+ macrophages expressed higher level of inflammatory factors directly.
All these data indicated that CD169+ sinus macrophage in mLNs played an essential
role on regulating mucosal inflammation.
PMID- 28694805
TI - Primary Immunodeficiency Diseases in Highly Consanguineous Populations from
Middle East and North Africa: Epidemiology, Diagnosis, and Care.
AB - Middle East and North Africa region (MENA) populations are of different ethnic
origins. Consanguineous marriages are common practice with an overall incidence
ranging between 20 and 50%. Primary immunodeficiency diseases (PIDs) are a group
of heterogeneous genetic disorders caused by defects in the immune system that
predisposes patients to recurrent infections, autoimmune diseases, and
malignancies. PIDs are more common in areas with high rates of consanguineous
marriage since most have an autosomal recessive mode of inheritance. Studies of
PIDs in the region had contributed into the discovery and the understanding of
several novel immunodeficiency disorders. Few MENA countries have established
national registries that helped in estimating the prevalence and defining common
PID phenotypes. Available reports from those registries suggest a predominance of
combined immunodeficiency disorders in comparison to antibody deficiencies seen
in other populations. Access to a comprehensive clinical immunology management
services is limited in most MENA countries. Few countries had established
advanced clinical immunology service, capable to provide extensive genetic
testing and stem cell transplantation for various immunodeficiency disorders.
Newborn screening for PIDs is an essential need in this population considering
the high incidence of illness and can be implemented and incorporated into
existing newborn screening programs in some MENA countries. Increased awareness,
subspecialty training in clinical immunology, and establishing collaborating
research centers are necessary to improve patient care. In this review, we
highlight some of the available epidemiological data, challenges in establishing
diagnosis, and available therapy for PID patients in the region.
PMID- 28694806
TI - A Bivalent Anthrax-Plague Vaccine That Can Protect against Two Tier-1 Bioterror
Pathogens, Bacillus anthracis and Yersinia pestis.
AB - Bioterrorism remains as one of the biggest challenges to global security and
public health. Since the deadly anthrax attacks of 2001 in the United States,
Bacillus anthracis and Yersinia pestis, the causative agents of anthrax and
plague, respectively, gained notoriety and were listed by the CDC as Tier-1
biothreat agents. Currently, there is no Food and Drug Administration-approved
vaccine against either of these threats for mass vaccination to protect general
public, let alone a bivalent vaccine. Here, we report the development of a single
recombinant vaccine, a triple antigen consisting of all three target antigens, F1
and V from Y. pestis and PA from B. anthracis, in a structurally stable context.
Properly folded and soluble, the triple antigen retained the functional and
immunogenicity properties of all three antigens. Remarkably, two doses of this
immunogen adjuvanted with Alhydrogel(r) elicited robust antibody responses in
mice, rats, and rabbits and conferred complete protection against inhalational
anthrax and pneumonic plague. No significant antigenic interference was observed.
Furthermore, we report, for the first time, complete protection of animals
against simultaneous challenge with Y. pestis and the lethal toxin of B.
anthracis, demonstrating that a single biodefense vaccine can protect against a
bioterror attack with weaponized B. anthracis and/or Y. pestis. This bivalent
anthrax-plague vaccine is, therefore, a strong candidate for stockpiling, after
demonstration of its safety and immunogenicity in human clinical trials, as part
of national preparedness against two of the deadliest bioterror threats.
PMID- 28694807
TI - Brucella Omp25 Upregulates miR-155, miR-21-5p, and miR-23b to Inhibit Interleukin
12 Production via Modulation of Programmed Death-1 Signaling in Human
Monocyte/Macrophages.
AB - Brucella spp. infection results in compromised Type1 (Th1) cellular immune
response. Several reports have described an immunomodulatory function for
Brucella major outer membrane protein Omp25. However, the mechanism by which
Omp25 modulates macrophage dysfunction has not been defined. Herein, we reported
that Omp25-deficient mutant of Brucella suis exhibited an enhanced ability to
induce interleukin (IL)-12 whereas ectopic expression of Omp25 protein inhibited
TLR agonists-induced IL-12 p70 production through suppression of both IL-12 p40
and p35 subunit expression in THP-1 cells. In addition, Omp25 significantly
upregulated miR-155, -23b and -21-5p, as well as the immunomodulator molecule
programmed death-1 (PD-1) in monocyte/macrophages. The upregulation of miR-155
and -23b correlated temporally with decreased TAB2 levels, IkappaB
phosphorylation and IL-12 p40 levels by targeting TAB2 and il12B 3' untranslated
region (UTR), respectively, while miR-21-5p increase directly led to the
reduction of lipopolysaccharide (LPS)/R848-induced IL-12 p35 protein by targeting
il12A 3'UTR. Consistent with this finding, reduction of miR-155 and -23b
attenuated the inhibitory effects of Omp25 on LPS/R848-induced IL-12 p40
expression at both transcriptional and posttranscriptional levels, while
reduction of miR-21-5p attenuated the inhibitory effects of Omp25 on LPS/R848
induced IL-12 p35 expression at the posttranscriptional level, together
significantly enhanced IL-12 p70 production upon LPS/R848 stimulation. We also
found that blocking PD-1 signaling decreased the expression of miR-155, -23b and
21-5p induced by Omp25 and enhanced IL-12 production in monocyte/macrophages.
Altogether, these data demonstrate that Brucella Omp25 induces miR-155, -23b and
21-5p to negatively regulate IL-12 production at both transcriptional and
posttranscriptional levels via regulation of PD-1 signaling, which provides an
entirely new mechanism underlying monocyte/macrophages dysfunction during
Brucella spp. infection.
PMID- 28694808
TI - Mycobacterium tuberculosis DosR Regulon Gene Rv2004c Encodes a Novel Antigen with
Pro-inflammatory Functions and Potential Diagnostic Application for Detection of
Latent Tuberculosis.
AB - Approximately 1.7 billion people in the world harbor latent Mycobacterium
tuberculosis (Mtb) with a substantial risk of progression to clinical outcome.
Containment of these seed beds of Mtb is essential to eliminate tuberculosis
completely in high burden settings such as India. Hence, there is an urgent need
for the identification of new serological markers for detection or vaccine
candidates to prevent latent tuberculosis infection (LTBI). DosR regulon antigens
of Mtb might serve as attractive targets for LTBI diagnosis or vaccine
development as they are specifically expressed and are upregulated during latent
phase. In this study, we investigated the role of Rv2004c, a member of DosR
regulon (exclusive to Mtb complex), in host-pathogen interaction and its
immunogenic potential in LTBI, active TB, and healthy control cohorts. Rv2004c
elicited strong antibody response in individuals with LTBI compared to active TB
patients and healthy cohorts. Recombinant Rv2004c induced pro-inflammatory
cytokine response in human peripheral blood mononuclear cells and THP-1 cells via
NF-kappaB phosphorylation. Interaction of Rv2004c with toll-like receptor (TLR)-2
was confirmed using HEK-Blue hTLR-2 and pull-down assays. Rv2004c enhanced the
surface expression of TLR-2 at mRNA and protein levels in THP-1 cells. Our
findings revealed that Rv2004c induces strong humoral and cell mediated immune
responses. Given these observations, we propose Rv2004c to be a potential
diagnostic marker or an attractive vaccine candidate that can be useful against
LTBI.
PMID- 28694809
TI - Unperturbed Cytotoxic Lymphocyte Phenotype and Function in Myalgic
Encephalomyelitis/Chronic Fatigue Syndrome Patients.
AB - Myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS) is a debilitating
disorder linked to diverse intracellular infections as well as physiological
stress. Cytotoxic lymphocytes combat intracellular infections. Their function is
attenuated by stress. Despite numerous studies, the role of cytotoxic lymphocytes
in ME/CFS remains unclear. Prompted by advances in the understanding of defects
in lymphocyte cytotoxicity, the discovery of adaptive natural killer (NK) cell
subsets associated with certain viral infections, and compelling links between
stress, adrenaline, and cytotoxic lymphocyte function, we reassessed the role of
cytotoxic lymphocytes in ME/CFS. Forty-eight patients from two independent
cohorts fulfilling the Canada 2003 criteria for ME/CFS were evaluated with
respect to cytotoxic lymphocyte phenotype and function. Results were compared to
values from matched healthy controls. Reproducible differences between patients
and controls were not found in cytotoxic lymphocyte numbers, cytotoxic granule
content, activation status, exocytotic capacity, target cell killing, or cytokine
production. One patient expressed low levels of perforin, explained by
homozygosity for the PRF1 p.A91V variant. However, overall, this variant was
present in a heterozygous state at the expected population frequency among ME/CFS
patients. No single patient displayed any pathological patterns of cellular
responses. Increased expansions of adaptive NK cells or deviant cytotoxic
lymphocyte adrenaline-mediated inhibition were not observed. In addition,
supervised dimensionality reduction analyses of the full, multidimensional
datasets did not reveal any reproducible patient/control discriminators. In
summary, employing sensitive assays and analyses for quantification of cytotoxic
lymphocyte differentiation and function, cytotoxicity lymphocyte aberrances were
not found among ME/CFS patients. These assessments of cytotoxic lymphocytes
therefore do not provide useful biomarkers for the diagnosis of ME/CFS.
PMID- 28694810
TI - Oxidized Hemoglobin Is Antigenic and Immunogenic in Lupus.
AB - Hemolysis-associated anemia is characteristic of diseases such as
atherosclerosis, lupus, malaria, and leishmaniasis; the toxic effects of free
hemoglobin (Hb) have been extensively described. This study was based on the
premise that release of this sequestered, inflammatory molecule can result in
deleterious immunological consequences, particularly in the context of pre
existing lupus. IgG anti-Hb responses were detected in the sera of lupus
patients. Lupus-prone mice exhibited heightened plasma Hb levels, and ferric
(Fe3+) Hb triggered preferential release of lupus-associated cytokines from
splenocytes derived from aging lupus-prone mice. Anti-Hb B cell precursor
frequencies were heightened in such mice, which also expressed increased titers
of anti-Hb antibodies in serum and in kidney eluates. Fe3+ Hb preferentially
increased the functional maturation of bone marrow-derived dendritic cells
(BMDCs) from lupus-prone mice, effects abrogated upon the inhibition of Stat3. Hb
interacted with lupus-associated autoantigens extruded during apoptosis and
coincubation of Hb and apoptotic blebs had additional maturation-inducing effects
on lupus BMDCs. Immunization with Hb in lupus-prone mice induced antigen
spreading to lupus-associated moieties; Hb-interacting autoantigens were
preferentially targeted and increased complement deposition and
glomerulosclerosis were observed. Hb therefore demonstrates both antigenicity and
immunogenicity and triggers specific immuno-pathological effects in a lupus
milieu.
PMID- 28694811
TI - Latent Cytomegalovirus (CMV) Infection Does Not Detrimentally Alter T Cell
Responses in the Healthy Old, But Increased Latent CMV Carriage Is Related to
Expanded CMV-Specific T Cells.
AB - Human cytomegalovirus (HCMV) primary infection and periodic reactivation of
latent virus is generally well controlled by T-cell responses in healthy people.
In older donors, overt HCMV disease is not generally seen despite the association
of HCMV infection with increased risk of mortality. However, increases in HCMV
DNA in urine of older people suggest that, although the immune response retains
functionality, immunomodulation of the immune response due to lifelong viral
carriage may alter its efficacy. Viral transcription is limited during latency to
a handful of viral genes and there is both an IFNgamma and cellular IL-10 CD4+ T
cell response to HCMV latency-associated proteins. Production of cIL-10 by HCMV
specific CD4+ T-cells is a candidate for aging-related immunomodulation. To
address whether long-term carriage of HCMV changes the balance of cIL-10 and
IFNgamma-secreting T-cell populations, we recruited a large donor cohort aged 23
78 years and correlated T-cell responses to 11 HCMV proteins with age, HCMV IgG
levels, latent HCMV load in CD14+ monocytes, and T-cell numbers in the blood.
IFNgamma responses by CD4+ and CD8+ T-cells to all HCMV proteins were detected,
with no age-related increase in this cohort. IL-10-secreting CD4+ T cell
responses were predominant to latency-associated proteins but did not increase
with age. Quantification of HCMV genomes in CD14+ monocytes, a known site of
latent HCMV carriage, did not reveal any increase in viral genome copies in older
donors. Importantly, there was a significant positive correlation between the
latent viral genome copy number and the breadth and magnitude of the IFNgamma T
cell response to HCMV proteins. This study suggests in healthy aged donors that
HCMV-specific changes in the T cell compartment were not affected by age and were
effective, as viremia was a very rare event. Evidence from studies of unwell aged
has shown HCMV to be an important comorbidity factor, surveillance of latent HCMV
load and low-level viremia in blood and body fluids, alongside typical
immunological measures and assessment of the antiviral capacity of the HCMV
specific immune cell function would be informative in determining if antiviral
treatment of HCMV replication in the old maybe beneficial.
PMID- 28694812
TI - Induction of Innate Immune Memory by Engineered Nanoparticles: A Hypothesis That
May Become True.
AB - Innate immune memory is the capacity of cells of the innate immune system, such
as monocytes and macrophages, to react differently to an inflammatory or
infectious challenge if previously exposed to the same or to another agent.
Innate immune memory is a protective mechanism, based on epigenetic
reprogramming, that ensures effective protection while limiting side effects of
tissue damage, by controlling innate/inflammatory responses to repeated
stimulations. Engineered nanoparticles (NPs) are novel challenges for our innate
immune system, and their ability to induce inflammatory activation, thereby
posing health risks, is currently being investigated with controversial results.
Besides their putative direct inflammation-inducing effects, we hypothesize that
engineered NPs may induce innate memory based on their capacity to induce
epigenetic modulation of gene expression. Preliminary results using non-toxic non
inflammatory gold NPs show that in fact NPs can induce memory by modulating in
either positive or negative fashion the inflammatory activation of human
monocytes to a subsequent bacterial challenge. The possibility of shaping
innate/inflammatory reactivity with NPs could open the way to future novel
approaches of preventive and therapeutic immunomodulation.
PMID- 28694813
TI - Intrapopulation Genotypic Variation of Foliar Secondary Chemistry during Leaf
Senescence and Litter Decomposition in Silver Birch (Betula pendula).
AB - Abundant secondary metabolites, such as condensed tannins, and their
interpopulation genotypic variation can remain through plant leaf senescence and
affect litter decomposition. Whether the intrapopulation genotypic variation of a
more diverse assortment of secondary metabolites equally persists through leaf
senescence and litter decomposition is not well understood. We analyzed
concentrations of intracellular phenolics, epicuticular flavonoid aglycones,
epicuticular triterpenoids, condensed tannins, and lignin in green leaves,
senescent leaves and partly decomposed litter of silver birch, Betula pendula.
Broad-sense heritability (H2) and coefficient of genotypic variation (CVG) were
estimated for metabolites in senescent leaves and litter using 19 genotypes
selected from a B. pendula population in southern Finland. We found that most of
the secondary metabolites remained through senescence and decomposition and that
their persistence was related to their chemical properties. Intrapopulation H2
and CVG for intracellular phenolics, epicuticular flavonoid aglycones and
condensed tannins were high and remarkably, increased from senescent leaves to
decomposed litter. The rank of genotypes in metabolite concentrations was
persistent through litter decomposition. Lignin was an exception, however, with a
diminishing genotypic variation during decomposition, and the concentrations of
lignin and condensed tannins had a negative genotypic correlation in the
senescent leaves. Our results show that secondary metabolites and their
intrapopulation genotypic variation can for the most part remain through leaf
senescence and early decomposition, which is a prerequisite for initial litter
quality to predict variation in litter decomposition rates. Persistent genotypic
variation also opens an avenue for selection to impact litter decomposition in B.
pendula populations through acting on their green foliage secondary chemistry.
The negative genotypic correlations and diminishing heritability of lignin
concentrations may, however, counteract this process.
PMID- 28694814
TI - Root Hair Mutations Displace the Barley Rhizosphere Microbiota.
AB - The rhizosphere, the thin layer of soil surrounding and influenced by plant
roots, defines a distinct and selective microbial habitat compared to unplanted
soil. The microbial communities inhabiting the rhizosphere, the rhizosphere
microbiota, engage in interactions with their host plants which span from
parasitism to mutualism. Therefore, the rhizosphere microbiota emerges as one of
the determinants of yield potential in crops. Studies conducted with different
plant species have unequivocally pointed to the host plant as a driver of the
microbiota thriving at the root-soil interface. Thus far, the host genetic traits
shaping the rhizosphere microbiota are not completely understood. As root hairs
play a critical role in resource exchanges between plants and the rhizosphere, we
hypothesized that they can act as a determinant of the microbiota thriving at the
root-soil interface. To test this hypothesis, we took advantage of barley
(Hordeum vulgare) mutant lines contrasting for their root hair characteristics.
Plants were grown in two agricultural soils, differentiating in their organic
matter contents, under controlled environmental conditions. At early stem
elongation rhizosphere specimens were collected and subjected to high-resolution
16S rRNA gene profiling. Our data revealed that the barley rhizosphere microbiota
is largely dominated by members of the phyla Bacteroidetes and Proteobacteria,
regardless of the soil type and the root hair characteristics of the host plant.
Conversely, ecological indices calculated using operational taxonomic units
(OTUs) presence, abundance, and phylogeny revealed a significant impact of root
hair mutations on the composition of the rhizosphere microbiota. In particular,
our data indicate that mutant plants host a reduced-complexity community compared
to wild-type genotypes and unplanted soil controls. Congruently, the host
genotype explained up to 18% of the variation in ecological distances computed
for the rhizosphere samples. Importantly, this effect is manifested in a soil
dependent manner. A closer inspection of the sequencing profiles revealed that
the root hair-dependent diversification of the microbiota is supported by a
taxonomically narrow group of bacteria, with a bias for members of the orders
Actinomycetales, Burkholderiales, Rhizobiales, Sphingomonadales, and
Xanthomonadales. Taken together, our results indicate that the presence and
function of root hairs are a determinant of the bacterial community thriving in
the rhizosphere and their perturbations can markedly impact on the recruitment of
individual members of the microbiota.
PMID- 28694815
TI - Co-overexpression of the Constitutively Active Form of OsbZIP46 and ABA-Activated
Protein Kinase SAPK6 Improves Drought and Temperature Stress Resistance in Rice.
AB - Drought is one of the major abiotic stresses threatening rice (Oryza sativa)
production worldwide. Drought resistance is controlled by multiple genes, and
therefore, a multi-gene genetic engineering strategy is theoretically useful for
improving drought resistance. However, the experimental evidence for such a
strategy is still lacking. In this study, a few drought-responsive genes from
rice were assembled by a multiple-round site-specific assembly system, and the
constructs were introduced into the rice cultivar KY131 via Agrobacterium
mediated transformation. The transgenic lines of the multi-gene and corresponding
single-gene constructs were pre-evaluated for drought resistance. We found that
the co-overexpression of two genes, encoding a constitutively active form of a
bZIP transcription factor (OsbZIP46CA1) and a protein kinase (SAPK6) involved in
the abscisic acid signaling pathway, showed significantly enhanced drought
resistance compared with the single-gene transgenic lines and the negative
transgenic plants. Single-copy lines of this bi-gene combination (named XL22) and
the corresponding single-gene lines were further evaluated for drought resistance
in the field using agronomical traits. The results showed that XL22 exhibited
greater yield, biomass, spikelet number, and grain number under moderate drought
stress conditions. The seedling survival rate of XL22 and the single-gene
overexpressors after drought stress treatment also supported the drought
resistance results. Furthermore, expression profiling by RNA-Seq revealed that
many genes involved in the stress response were specifically up-regulated in the
drought-treated XL22 lines and some of the stress-related genes activated in CA1
OE and SAPK6-OE were distinct, which could partially explain the different
performances of these lines with respect to drought resistance. In addition, the
XL22 seedlings showed improved tolerance to heat and cold stresses. Our results
demonstrate that the multi-gene assembly in an appropriate combination may be a
promising approach in the genetic improvement of drought resistance.
PMID- 28694816
TI - Physiological and Transcriptional Changes of Three Citrus Rootstock Seedlings
under Iron Deficiency.
AB - Iron is an essential micronutrient for plants, and plants have evolved adaptive
mechanisms to improve iron acquisition from soils. Grafting on iron deficiency
tolerant rootstock is an effective strategy to prevent iron deficiency-chlorosis
in fruit-tree crops. To determine the mechanisms underlying iron uptake in iron
deficiency, two iron deficiency-tolerant citrus rootstocks, Zhique (ZQ) and
Xiangcheng (XC), as well as iron deficiency-sensitive rootstock trifoliate orange
(TO) seedlings were studied. Plants were grown in hydroponics system for 100
days, having 50 MUM iron (control) and 0 MUM iron (iron deficiency) nutrient
solution. Under iron deficiency, more obvious visual symptoms of iron chlorosis
were observed in the leaves of TO, whereas slight symptoms were observed in ZQ
and XC. This was further supported by the lower chlorophyll concentration in the
leaves of TO than in leaves of ZQ and XC. Ferrous iron showed no differences
among the three citrus rootstock roots, whereas ferrous iron was significantly
higher in leaves of ZQ and XC than TO. The specific iron absorption rate and leaf
iron proportion were significantly higher in ZQ and XC than in TO, suggesting the
iron deficiency tolerance can be explained by increased iron uptake in roots of
ZQ and XC, allowed by subsequent translocation to shoots. In transcriptome
analysis, 29, 298, and 500 differentially expressed genes (DEGs) in response to
iron deficiency were identified in ZQ, XC, and TO, respectively (Fold change >= 2
and Probability >= 0.8 were used as thresholds to identify DEGs). A Gene Ontology
analysis suggested that several genotype-specific biological processes are
involved in response to iron deficiency. Genes associated with cell wall
biosynthesis, ethylene and abscisic acid signal transduction pathways were
involved in iron deficiency responses in citrus rootstocks. The results of this
study provide a basis for future analyses of the physiological and molecular
mechanisms of the tolerance of different citrus rootstocks to iron deficiency.
PMID- 28694817
TI - Tissue-Specific Regulation of Gma-miR396 Family on Coordinating Development and
Low Water Availability Responses.
AB - Previously, it was reported that miR396s interact with growth-regulating factors
(GRFs) to modulate plant growth, development, and stress resistance. In soybean,
11 gma-miR396 precursors (Pre-miR396a-k) were found, and 24 GmGRFs were predicted
as targets of seven mature gma-miR396s (gma-miR396a/b/c/e/h/i/k). To explore the
roles of the miR396-GRF module in low water availability response of soybean, we
analyzed the expression of Pre-miR396a-k, and found that Pre-miR396a/i/bdgk/e/h
were up-regulated in leaves and down-regulated in roots; on the contrary,
GmGRF5/6/7/8/15/17/21 were down-regulated in leaves and
GmGRF1/2/17/18/19/20/21/22/23/24 were up-regulated in roots of low water
potential stressed soybean. Any one of gma-miR396a/b/c/e/h/i/k was able to
interact with 20 GmGRFs (GmGRF1/2/6-11/13-24), confirming that this module
represents a multi-to-multi network interaction. We generated Arabidopsis plants
over-expressing each of the 11 gma-miR396 precursors (Pre-miR396a-k), and seven
of them (miR396a/b/c/e/h/i/k-OE transgenic Arabidopsis) showed altered
development. The low water availability of miR396a/b/c/e/h/i/k-OE was enhanced in
leaves but reduced in seeds and roots. Contrary to previous reports,
miR396a/b/c/i-OE seedlings showed lower survival rate than WT when recovering
after rewatering under soil drying. In general, we believe our findings are
valuable to understand the role of gma-miR396 family in coordinating development
and low water availability responses, and can provide potential strategies and
directions for soybean breeding programs to improve seed yield and plant drought
tolerance.
PMID- 28694818
TI - Insights into the Molecular Events That Regulate Heat-Induced Chilling Tolerance
in Citrus Fruits.
AB - Low non-freezing temperature may cause chilling injury (CI), which is responsible
for external quality deterioration in many chilling-sensitive horticultural
crops. Exposure of chilling-sensitive citrus cultivars to non-lethal high
temperature conditioning may increase their chilling tolerance. Very little
information is available about the molecular events involved in such tolerance.
In this work, the molecular events associated with the low temperature tolerance
induced by heating Fortune mandarin, which is very sensitive to chilling, for 3
days at 37 degrees C prior to cold storage is presented. A transcriptomic
analysis reveals that heat-conditioning has an important impact favoring the
repression of genes in cold-stored fruit, and that long-term heat-induced
chilling tolerance is an active process that requires activation of transcription
factors involved in transcription initiation and of the WRKY family. The analysis
also shows that chilling favors degradation processes, which affect lipids and
proteins, and that the protective effect of the heat-conditioning treatment is
more likely to be related to the repression of the genes involved in lipid
degradation than to the modification of fatty acids unsaturation, which affects
membrane permeability. Another major factor associated with the beneficial effect
of the heat treatment on reducing CI is the regulation of stress-related
proteins. Many of the genes that encoded such proteins are involved in secondary
metabolism and in oxidative stress-related processes.
PMID- 28694819
TI - Assessment of Vegetation Indices Derived by UAV Imagery for Durum Wheat
Phenotyping under a Water Limited and Heat Stressed Mediterranean Environment.
AB - There is growing interest for using Spectral Vegetation Indices (SVI) derived by
Unmanned Aerial Vehicle (UAV) imagery as a fast and cost-efficient tool for plant
phenotyping. The development of such tools is of paramount importance to continue
progress through plant breeding, especially in the Mediterranean basin, where
climate change is expected to further increase yield uncertainty. In the present
study, Normalized Difference Vegetation Index (NDVI), Simple Ratio (SR) and Green
Normalized Difference Vegetation Index (GNDVI) derived from UAV imagery were
calculated for two consecutive years in a set of twenty durum wheat varieties
grown under a water limited and heat stressed environment. Statistically
significant differences between genotypes were observed for SVIs. GNDVI explained
more variability than NDVI and SR, when recorded at booting. GNDVI was
significantly correlated with grain yield when recorded at booting and anthesis
during the 1st and 2nd year, respectively, while NDVI was correlated to grain
yield when recorded at booting, but only for the 1st year. These results suggest
that GNDVI has a better discriminating efficiency and can be a better predictor
of yield when recorded at early reproductive stages. The predictive ability of
SVIs was affected by plant phenology. Correlations of grain yield with SVIs were
stronger as the correlations of SVIs with heading were weaker or not significant.
NDVIs recorded at the experimental site were significantly correlated with grain
yield of the same set of genotypes grown in other environments. Both positive and
negative correlations were observed indicating that the environmental conditions
during grain filling can affect the sign of the correlations. These findings
highlight the potential use of SVIs derived by UAV imagery for durum wheat
phenotyping under low yielding Mediterranean conditions.
PMID- 28694821
TI - Mathematical modelling of vector-borne diseases and insecticide resistance
evolution.
AB - BACKGROUND: Vector-borne diseases are important public health issues and,
consequently, in silico models that simulate them can be useful. The susceptible
infected-recovered (SIR) model simulates the population dynamics of an epidemic
and can be easily adapted to vector-borne diseases, whereas the Hardy-Weinberg
model simulates allele frequencies and can be used to study insecticide
resistance evolution. The aim of the present study is to develop a coupled system
that unifies both models, therefore enabling the analysis of the effects of
vector population genetics on the population dynamics of an epidemic. METHODS:
Our model consists of an ordinary differential equation system. We considered the
populations of susceptible, infected and recovered humans, as well as susceptible
and infected vectors. Concerning these vectors, we considered a pair of alleles,
with complete dominance interaction that determined the rate of mortality induced
by insecticides. Thus, we were able to separate the vectors according to the
genotype. We performed three numerical simulations of the model. In simulation
one, both alleles conferred the same mortality rate values, therefore there was
no resistant strain. In simulations two and three, the recessive and dominant
alleles, respectively, conferred a lower mortality. RESULTS: Our numerical
results show that the genetic composition of the vector population affects the
dynamics of human diseases. We found that the absolute number of vectors and the
proportion of infected vectors are smaller when there is no resistant strain,
whilst the ratio of infected people is larger in the presence of insecticide
resistant vectors. The dynamics observed for infected humans in all simulations
has a very similar shape to real epidemiological data. CONCLUSION: The population
genetics of vectors can affect epidemiological dynamics, and the presence of
insecticide-resistant strains can increase the number of infected people. Based
on the present results, the model is a basis for development of other models and
for investigating population dynamics.
PMID- 28694820
TI - WHITE STRIPE LEAF4 Encodes a Novel P-Type PPR Protein Required for Chloroplast
Biogenesis during Early Leaf Development.
AB - Pentatricopeptide repeat (PPR) proteins comprise a large family in higher plants
and perform diverse functions in organellar RNA metabolism. Despite the rice
genome encodes 477 PRR proteins, the regulatory effects of PRR proteins on
chloroplast development remains unknown. In this study, we report the functional
characterization of the rice white stripe leaf4 (wsl4) mutant. The wsl4 mutant
develops white-striped leaves during early leaf development, characterized by
decreased chlorophyll content and malformed chloroplasts. Positional cloning of
the WSL4 gene, together with complementation and RNA-interference tests, reveal
that it encodes a novel P-family PPR protein with 12 PPR motifs, and is localized
to chloroplast nucleoids. Quantitative RT-PCR analyses demonstrate that WSL4 is a
low temperature response gene abundantly expressed in young leaves. Further
expression analyses show that many nuclear- and plastid-encoded genes in the wsl4
mutant are significantly affected at the RNA and protein levels. Notably, the
wsl4 mutant causes defects in the splicing of atpF, ndhA, rpl2, and rps12. Our
findings identify WSL4 as a novel P-family PPR protein essential for chloroplast
RNA group II intron splicing during early leaf development in rice.
PMID- 28694822
TI - Chemical Composition and Cytotoxic and Antibacterial Activities of the Essential
Oil of Aloysia citriodora Palau Grown in Morocco.
AB - The aim of this work is to investigate the in vitro cytotoxic and antibacterial
effects of the essential oils of Aloysia citriodora Palau, harvested in different
regions of Morocco. The chemical profile was established using gas chromatography
mass spectrometry analysis. The cytotoxic activity against P815, MCF7, and VERO
cell lines as well as the normal human peripheral blood mononuclear cells (PBMCs)
was evaluated using the MTT assay. Standard, ATCC, strains of bacteria
(Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa) were
cultivated in Muller Hinton media. Then, agar disc diffusion, minimum inhibitory
concentrations (MICs), and minimal bactericidal concentrations (MBCs) were
determined using microdilution method. The essential oils obtained were
predominantly composed of beta-spathulenol (15.61%), Ar-curcumene (14.15%), trans
caryophyllene oxide (14.14%), and neral (10.02%). The results of the assays
showed that the cytotoxic effect of the essential oil of A. citriodora was high
on P815 and moderate on MCF7 and on VERO cell lines. However, no cytotoxic effect
was observed on PBMCs. On the other hand, essential oils showed a significant
antimicrobial activity against both Gram-negative and Gram-positive bacteria.
MICs ranged between 2.84 and 8.37 mg/ml. Essential oil of A. citriodora leaves
possesses significant antibacterial effect and cytotoxic activity against tumor
cell lines.
PMID- 28694823
TI - The Persistence of Silodosin Monotherapy and the Reasons for Withdrawal from
Treatment of Previously Untreated Japanese Patients with Lower Urinary Tract
Symptoms Suggestive of Benign Prostatic Hyperplasia.
AB - OBJECTIVES: The persistence of silodosin and the reasons for withdrawal from
treatment of previously untreated Japanese patients with lower urinary tract
symptoms suggestive of benign prostatic hyperplasia (LUTS/BPH) were evaluated in
real-life clinical practice. METHODS: A total of 81 previously untreated Japanese
patients diagnosed with LUTS/BPH were treated with silodosin monotherapy and
prospectively followed for 4 years. The persistence rate was estimated using the
Kaplan-Meier method. If silodosin had to be terminated or a patient did not come
to the hospital, the reason was determined. RESULTS: The 6-month, 1-year, 2-year,
3-year, and 4-year persistence rates were 63.0%, 56.8%, 50.6%, 44.4%, and 35.8%,
respectively. The most frequent reason (22.2%) for withdrawal was symptom
resolution. After silodosin treatment, the international prostate symptom score
and the quality of life index were significantly improved and maintained for 4
years. CONCLUSIONS: 35.8% of previously untreated Japanese patients continued
silodosin for 4 years. Many patients terminated silodosin for various reasons,
the most frequent of which was symptom resolution. The effects of silodosin were
maintained when the patients continued treatment. TRIAL REGISTRATION: This study
was approved by the institutional review board of Hokkaido Prefectural Esashi
Hospital (number 2007-2) and was registered in a public trial registry
(UMIN000026910).
PMID- 28694824
TI - Burden and Correlates of Falls among Rural Elders of South India: Mobility and
Independent Living in Elders Study.
AB - AIM: Falls are an important contributor to loss of function, morbidity, and
mortality in elders. Little is known about falls in Indian populations. The
objective of this cross-sectional report was to identify the prevalence and
correlates of falls in a cohort of 562 rural southern Indian men and women.
METHODS: Risk factors included demographics, anthropometrics, self-reported
health, medical history, physical function, vision, depression, and lifestyle.
Odds ratios were calculated using logistic regression. RESULTS: 71 (13%) subjects
reported at least 1 fall in the past year. Prevalence was higher among women
(17%) than men (8%), P = 0.003. Sex and age showed significant interaction (P =
0.04) whereby falls prevalence increased with age among women but decreased among
men. Correlates of falls among men included a history of osteoarthritis (OA)
(odds ratio (OR): 6.91; 95% CI: 1.4-33.1), depression (OR:9.6; 3.1-30.1), and
greater height (OR per 1 standard deviation increase: 2.33; 1.1-5.1). Among
women, poor physical performance (OR: 3.33; 1.13-9.86) and history of
cardiovascular disease (CVD) (OR: 2.42; 1.01-5.80) were independently associated
with falls. IMPLICATIONS: Prevalence of falls in elderly South Indians was lower
than published reports from western countries and likely reflects low exposure to
fall risks. Patterns with age differed in men and women and may reflect sex
differences in the accuracy of age recall. Presence of comorbidities specifically
OA, CVD, and depression was independent correlate of falling.
PMID- 28694825
TI - Rapid Separation of Indole Glucosinolates in Roots of Chinese Cabbage (Brassica
rapa Subsp. Pekinensis) by High-Performance Liquid Chromatography with Diode
Array Detection.
AB - Glucosinolates are a class of sulphur-containing plant compounds with diverse
biological properties. They have been found exclusively in the Brassicaceae
family plants and studied exhaustively in biosynthetic and application
perspectives. The aim of this current study is to present a simple and updated
method to quantify indole glucosinolate content in hairy root cultures of Chinese
cabbage by HPLC-DAD-UV/Vis. Method validation controls were performed and
recovery experiments were assayed. The data was statically treated and compared
with published works. The current method allowed a feasible identification of
indole glucosinolates and it was possible to identify accurately three indole
glucosinolate compounds (glucobrassicin, 4-methoxyglucobrassicin, and 1
methoxyglucobrassicin) in roots of Chinese cabbage. The method demonstrated a
good linearity (R2 > 0.99), a good precision, and selectivity sensitivity. In
conclusion, this protocol provides an accessible method to extract and quantify
glucosinolates in plant samples. Thus, based on our results, the method is valid
and can be extended to other plant or food matrices.
PMID- 28694826
TI - Magnesium Oxide Nanoparticles Reinforced Electrospun Alginate-Based Nanofibrous
Scaffolds with Improved Physical Properties.
AB - Mechanically robust alginate-based nanofibrous scaffolds were successfully
fabricated by electrospinning method to mimic the natural extracellular matrix
structure which benefits development and regeneration of tissues. Alginate-based
nanofibres were electrospun from an alginate/poly(vinyl alcohol) (PVA)
polyelectrolyte complex. SEM images revealed the spinnability of the complex
composite nanofibrous scaffolds, showing randomly oriented, ultrafine, and
virtually defects-free alginate-based/MgO nanofibrous scaffolds. Here, it is
shown that an alginate/PVA complex scaffold, blended with near-spherical MgO
nanoparticles (? 45 nm) at a predetermined concentration (10% (w/w)), is
electrospinnable to produce a complex composite nanofibrous scaffold with
enhanced mechanical stability. For the comparison purpose, chemically cross
linked electrospun alginate-based scaffolds were also fabricated. Tensile test to
rupture revealed the significant differences in the tensile strength and elastic
modulus among the alginate scaffolds, alginate/MgO scaffolds, and cross-linked
alginate scaffolds (P < 0.05). In contrast to cross-linked alginate scaffolds,
alginate/MgO scaffolds yielded the highest tensile strength and elastic modulus
while preserving the interfibre porosity of the scaffolds. According to the
thermogravimetric analysis, MgO reinforced alginate nanofibrous scaffolds
exhibited improved thermal stability. These novel alginate-based/MgO scaffolds
are economical and versatile and may be further optimised for use as
extracellular matrix substitutes for repair and regeneration of tissues.
PMID- 28694827
TI - Preferred M2 Polarization by ASC-Based Hydrogel Accelerated Angiogenesis and
Myogenesis in Volumetric Muscle Loss Rats.
AB - Volumetric muscle loss (VML) injury resulted from massive muscle defects and
diseases for which there are still no effective therapeutic treatments. This
study aimed to investigate the effects of rat adipose-derived mesenchymal stem
cells (rASCs) and rASCs-conditioned medium- (CM-) based type I collagen hydrogel
on macrophage (MP) transition, myogenesis, and vascularization in the rat VML
model. Laser Doppler results demonstrated much higher blood flow in the rASC- and
CM-based hydrogel groups. qRT-PCR, hematoxylin and eosin, immunofluorescence, and
Sirius Red staining manifested that both rASCs and CM-based hydrogel implantation
accelerated muscle repair with upregulated angiogenesis and myogenesis,
attenuated inflammation while facilitating M2 transition, and decreased the
collagen deposition compared with the hydrogel group. In vitro experiments
indicated that factors secreted from polarized M2 MPs could accelerate the
migration and tube formation capacities of HUVECs. These results suggested that
rASCs exerted immunomodulatory effects on MPs which further enhanced the
proangiogenic potential on ECs to promote myogenesis and angiogenesis during
muscle repair. These fundamental results support further clinical applications of
ASCs for muscle loss injury.
PMID- 28694828
TI - Prevalence and Risk Factors of Delayed Sputum Conversion among Patients Treated
for Smear Positive PTB in Northwestern Rural Tanzania: A Retrospective Cohort
Study.
AB - INTRODUCTION: Smear positive TB carries high morbidity and mortality. The TB
treatment aims at sputum conversion by two months of antituberculous. Patients
who delay sputum conversion remain potentially infectious, with risk of treatment
failure, drug resistance, and mortality. Little is known about the magnitude of
this problem in our setting. This study was designed to determine the prevalence
and risk factors of delayed sputum conversion in northwestern rural part of
Tanzania. METHODS: This was a retrospective cohort study involving smear positive
TB patients at Sengerema DDH in 2015. Demographic data, HIV status, and sputum
results at TB diagnosis and on TB treatment were collected and analyzed using
STATA 11. RESULTS: In total, 156 patients were studied. Males were 97 (62%); the
median age was 39 [30-51] years. Fifty-five (35.3%) patients were HIV coinfected
and 13 (8.3%) patients had delayed sputum conversion which was strongly
associated with male gender (OR = 8.2, p = 0.046), age >50 years (OR = 6.7, p =
0.003), and AFB 3+ (OR = 8.1, p = 0.008). CONCLUSIONS: Delayed sputum conversion
is prevalent in this study. These patients can potentially fail on treatment,
develop drug resistance, and continue spreading TB. Strategies to reduce the rate
of delayed sputum conversion could also reduce these potential unfavorable
outcomes.
PMID- 28694829
TI - Physical Trauma among Refugees: Comparison between Refugees and Local Population
Who Were Admitted to Emergency Department-Experience of a State Hospital in
Syrian Border District.
AB - BACKGROUND: Hundreds of thousands of people have fled to Turkey since the civil
war started in Syria in 2011. Refugees and local residents have been facing
various challenges such as sociocultural and economic ones and access to health
services. Trauma exposure is one of the most important and underestimated health
problems of refugees settling in camps. AIMS: We aimed to evaluate refugee
admissions to emergency department because of trauma in means of demographics of
patients and mechanism of trauma and compare the results with the local
population. METHODS: Retrospective evaluation of results and comparison with the
results of local population. RESULTS: We determined that the ratio of emergency
admission of refugee patients because of trauma was significantly higher than the
local population for most types of trauma. CONCLUSION: Further studies with more
refugee participants are needed to fully understand the underlying reasons for
this high ratio to protect refugees as well as for planning to take caution to
attenuate the burden on healthcare systems.
PMID- 28694830
TI - Erratum to: Do epinephrine auto-injectors have an unsuitable needle length in
children and adolescents at risk for anaphylaxis from food allergy?
AB - [This corrects the article DOI: 10.1186/s13223-016-0110-8.].
PMID- 28694831
TI - Molecular Identification of Mycobacterium Species of Public Health and Veterinary
Importance from Cattle in the South State of Mexico.
AB - Mycobacterium genus causes a variety of zoonotic diseases. The best known example
is the zoonotic tuberculosis due to M. bovis. Much less is known about
"nontuberculous mycobacteria (NTM)," which are also associated with infections in
humans. The Mexican standard NOM-ZOO-031-1995 regulates the presence of M. bovis
in cattle; however, no regulation exists for the NTM species. The objective of
this study was to isolate and identify nontuberculous mycobacteria species from
cattle of local herds in the south region of the State of Mexico through the
identification and detection of the 100 bp molecular marker in the 23S rRNA gene
with subsequent sequencing of the 16S rRNA gene. Milk samples (35) and nasal
exudate samples (68) were collected. From the 108 strains isolated, 39 were
selected for identification. Thirteen strains isolated from nasal exudates
amplified the 100 bp molecular marker and were identified as M. neoaurum (six
strains), M. parafortuitum (four strains), M. moriokaense (two strains), and M.
confluentis (one strain). Except M. parafortuitum, the other species identified
are of public health and veterinary concern because they are pathogenic to
humans, especially those with underlying medical conditions.
PMID- 28694832
TI - Pathogenicity of Virulent Species of Group C Streptococci in Human.
AB - Group C streptococci (GCS) are livestock pathogens and they often cause zoonotic
diseases in humans. They are Gram-positive, in mostly beta-hemolytic and
facultative anaerobes. Because of their close evolutionary kinship with group A
streptococci (GAS), GCS share many common virulence factors with GAS and cause a
similar range of diseases. Due to the exchange of genetic material with GAS, GCS
belong to bacteria that are difficult to be distinguished from group A
streptococci; GCS are often treated in microbiological diagnostics as
contamination of the culture. This report focuses mainly on the pathogenicity of
virulent species of GCS and their association with human diseases. The condition
that is most frequently quoted is pharyngitis. In this paper, the virulence
factors have also been mentioned and an interesting link has been made between
GCS and the pathogenesis of rheumatic diseases among the native people of India
and Aboriginal populations.
PMID- 28694833
TI - Huanglian-Jie-Du-Tang Extract Ameliorates Depression-Like Behaviors through BDNF
TrkB-CREB Pathway in Rats with Chronic Unpredictable Stress.
AB - Neuroinflammation is considered as one of the common pathogeneses of depression.
Huanglian-Jie-Du-Tang (HJDT) is a traditional Chinese herbal formula. The present
study investigates the antidepressant-like effect of HJDT and its possible
mechanism in rats. Rats were given HJDT (2, 4, and 8 g/kg, intragastrically),
paroxetine (1.8 mg/kg, intragastrically), or an equivalent volume of saline for
42 days. The depression-related behaviors, including sucrose preference test
(SPT), open field test (OFT), novel objective recognition task (NORT), and forced
swimming test (FST), were detected. 5-Hydroxytryptamine (5-HT) and dopamine (DA)
contents, microglial activation, proinflammatory cytokines, and brain derived
neurotrophic factor (BDNF), tropomyosin receptor kinases B (TrkB), and cAMP
responsive element binding protein (CREB) expression were investigated. The
results indicated HJDT (2 and 4 g/kg) dramatically ameliorated the depression
like behaviors. Also HJDT decreased the number of microglia and the
proinflammatory cytokines in hippocampus. Western-blotting analysis displayed
HJDT upregulated BDNF, TrkB, and pCREB/CREB expression in hippocampus.
Particularly, pCREB DNA activity enhanced with HJDT treatment in hippocampus. But
there was no difference in the 5-HT and DA contents with HJDT treatment. In
conclusion, it was supposed that HJDT might be a potential Chinese medicine
decoction for treating or alleviating complex symptoms of depression through BDNF
TrkB-CREB pathway.
PMID- 28694834
TI - Influenza vaccine response in community-dwelling German prefrail and frail
individuals.
AB - BACKGROUND: The age-related dysregulation of the immune system in older persons
results in reduced responses to vaccination and greater susceptibility to
infection, especially in frail individuals who suffer the greatest of morbidity
and mortality due to infection. Recently, significantly reduced anti-influenza
antibody titers and increased rates of influenza infection after vaccination were
reported in community-dwelling American frail older adults. The aim of our study
was to further assess the relative impact of frailty and of each individual Fried
frailty criterion on influenza vaccine response. Prefrail and frail community
dwelling German persons aged >=70 years were recruited for a nutritional
randomized double-blind placebo-controlled clinical trial conducted during the
2014-2015 influenza season. Herein, we present a sub-analysis study of the
placebo group to compare 76 prefrail and frail participants. RESULTS: Previous
seasonal influenza vaccination rate was relatively high (77.6%) in the 76
volunteers aged from 70 to 93 years. Of these participants, 65.8% were diagnosed
as prefrail and 34.2% as frail according to the Fried frailty criteria. In both
prefrail and frail groups, elevated levels of pre-vaccination seroprotection were
observed to all vaccine strains (H1N1: 54% and 32%, H3N2: 60% and 72%, B: 10% and
16%). Post-vaccination, similar increases in haemagglutination-inhibiting
antibody titers were observed for the three vaccine strains in both prefrail and
frail groups. No significant difference in geometric mean titer (GMT) ratios and
in rates of seroconversion or seroprotection were observed between prefrail and
frail groups. Regarding the five Fried frailty criteria, only participants with
low physical activity had significantly lower GMT to the strains H3N2 (55.4 vs
103.7, p = 0.001) and B (13.9 vs 20.0, p = 0.06), as compared to those having
normal physical activity. CONCLUSIONS: Influenza vaccine response was not
significantly affected by the frail phenotype, as defined by Fried frailty
criteria, in community-dwelling German individuals. However, low physical
activity may be a relevant predictor of lower serological response in vaccinated
older individuals. TRIAL REGISTRATION: Clinicaltrials.gov NCT02262091 (October 8,
2013).
PMID- 28694835
TI - Myoepithelioma of soft tissue in the gluteal region: Diagnostic pitfall in
cytology.
PMID- 28694836
TI - Metastatic prostatic stromal sarcoma: A challenging diagnosis on fine-needle
aspiration with broad differential diagnosis.
AB - Prostatic stromal sarcomas (PSS) are rare solid organ mesenchymal sarcomas. PSS
may pose difficult diagnostic challenges on fine needle aspiration biopsy. We
report a 48-year-old man diagnosed with metastatic high grade prostatic stromal
sarcoma by a CT-scan guided fine needle aspiration (FNA) biopsy of a right lower
lung lobe nodule. We reviewed the literature on the epidemiologic, cyto
histological, and immunophenotypic findings and discussed the differential
diagnosis for this rare entity.
PMID- 28694837
TI - Metastatic neoplasms to the thyroid diagnosed by fine-needle aspiration/core
needle biopsy: Clinicopathologic and cytomorphologic correlation.
AB - BACKGROUND: Although thyroid fine-needle aspiration (FNA) and core needle biopsy
(CNB) are commonly utilized modalities in the evaluation of thyroid nodules,
metastatic tumors to the thyroid are only rarely encountered. We aspired to
determine the incidence and primary origin of metastases to the thyroid at our
institution and to examine their clinicopathologic and cytomorphologic features.
MATERIALS AND METHODS: A search of our database was undertaken to review all
thyroid FNA and/or CNB examined between January 2004 and December 2013. RESULTS:
During our 10 year study period, 7497 patients underwent 13,182 FNA and/or CNB.
Four hundred sixty one (6%) patients were diagnosed with neoplasms. Only five
(1.1%) were found to have metastatic tumors to the thyroid involving three
females and two males. Two were diagnosed by FNA, one by CNB, and two by both FNA
and CNB, with rapid on-site evaluation (ROSE) employed in all cases. The primary
malignancies in the five cases were pulmonary and nasopharyngeal squamous cell
carcinomas, renal cell carcinoma, pancreatic adenocarcinoma, and olfactory
neuroblastoma. The cytomorphologic features of these metastases to the thyroid
aided in their distinction from primary thyroid carcinoma. Two of these
metastases, a renal cell carcinoma and pancreatic adenocarcinoma, were the first
clinical manifestations of cancer. CONCLUSION: Metastases to the thyroid
diagnosed by FNA and/or CNB are exceedingly rare in our institution, comprising
only 0.04% of total FNA/CNB and only 1.1% of all thyroid neoplasms. We report the
first known case of metastatic olfactory neuroblastoma to the thyroid diagnosed
by aspiration cytology. In addition, an occult primary may present as a thyroid
mass on FNA or CNB as occurred with two of our cases. FNA/CNB proved to be highly
effective in the diagnosis of metastases to the thyroid, with ROSE proving
valuable in assuring specimen adequacy. Thyroid FNA and CNB demonstrated great
utility in the setting of metastatic disease, obviating the need for more
invasive procedures.
PMID- 28694838
TI - How animals distribute themselves in space: variable energy landscapes.
AB - BACKGROUND: Foraging efficiency determines whether animals will be able to raise
healthy broods, maintain their own condition, avoid predators and ultimately
increase their fitness. Using accelerometers and GPS loggers, features of the
habitat and the way animals deal with variable conditions can be translated into
energetic costs of movement, which, in turn, can be translated to energy
landscapes.We investigated energy landscapes in Gentoo Penguins Pygoscelis papua
from two colonies at New Island, Falkland/Malvinas Islands. RESULTS: In our
study, the marine areas used by the penguins, parameters of dive depth and the
proportion of pelagic and benthic dives varied both between years and colonies.
As a consequence, the energy landscapes also varied between the years, and we
discuss how this was related to differences in food availability, which were also
reflected in differences in carbon and nitrogen stable isotope values and
isotopic niche metrics. In the second year, the energy landscape was
characterized by lower foraging costs per energy gain, and breeding success was
also higher in this year. Additionally, an area around three South American Fur
Seal Arctocephalus australis colonies was never used. CONCLUSIONS: These results
confirm that energy landscapes vary in time and that the seabirds forage in areas
of the energy landscapes that result in minimized energetic costs. Thus, our
results support the view of energy landscapes and fear of predation as mechanisms
underlying animal foraging behaviour. Furthermore, we show that energy landscapes
are useful in linking energy gain and variable energy costs of foraging to
breeding success.
PMID- 28694839
TI - Gene expression profiling of whole blood cells supports a more efficient
mitochondrial respiration in hypoxia-challenged gilthead sea bream (Sparus
aurata).
AB - BACKGROUND: Acclimation to abiotic challenges, including decreases in O2
availability, requires physiological and anatomical phenotyping to accommodate
the organism to the environmental conditions. The retention of a nucleus and
functional mitochondria in mature fish red blood cells makes blood a promising
tissue to analyse the transcriptome and metabolic responses of hypoxia-challenged
fish in an integrative and non-invasive manner. METHODS: Juvenile gilthead sea
bream (Sparus aurata) were reared at 20-21 degrees C under normoxic conditions
(> 85% O2 saturation) followed by exposure to a gradual decrease in water O2
concentration to 3.0 ppm (41-42% O2 saturation) for 24 h or 1.3 ppm (18-19% O2
saturation) for up to 4 h. Blood samples were collected at three different
sampling points for haematological, biochemical and transcriptomic analysis.
RESULTS: Blood physiological hallmarks remained almost unaltered at 3.0 ppm, but
the haematocrit and circulating levels of haemoglobin, glucose and lactate were
consistently increased when fish were maintained below the limiting oxygen
saturation at 1.3 ppm. These findings were concurrent with an increase in total
plasma antioxidant activity and plasma cortisol levels, whereas the opposite
trend was observed for growth-promoting factors, such as insulin-like growth
factor I. Additionally, gene expression profiling of whole blood cells revealed
changes in upstream master regulators of mitochondria (pgcbeta and nrf1),
antioxidant enzymes (gpx1, gst3, and sod2), outer and inner membrane translocases
(tom70, tom22, tim44, tim10, and tim9), components of the mitochondrial dynamics
system (mfn2, miffb, miro1a, and miro2), apoptotic factors (aifm1), uncoupling
proteins (ucp2) and oxidative enzymes of fatty acid beta-oxidation (acca2, ech,
and hadh), the tricarboxylic acid cycle (cs) and the oxidative phosphorylation
pathway. The overall response is an extensive reduction in gene expression of
almost all respiratory chain enzyme subunits of the five complexes, although
mitochondrial-encoded catalytic subunits and nuclear-encoded regulatory subunits
of Complex IV were primarily increased in hypoxic fish. CONCLUSIONS: Our results
demonstrate the re-adjustment of mitochondrial machinery at transcriptional level
to cope with a decreased basal metabolic rate, consistent with a low risk of
oxidative stress, diminished aerobic ATP production and higher O2-carrying
capacity. Taken together, these results suggest that whole blood cells can be
used as a highly informative target tissue of metabolic condition.
PMID- 28694840
TI - Hepatic, adipocyte, enteric and pancreatic hormones: response to dietary
macronutrient composition and relationship with metabolism.
AB - BACKGROUND: We sought to characterize the effects of dietary macronutrient
composition on various hormones implicated in the regulation of insulin
sensitivity (IS) and energy expenditure (EE). METHODS: Following 10-15% weight
loss, 21 overweight subjects consumed 3 weight-loss maintenance diets [low fat
(LF), low glycemic index (LGI) and very low carbohydrate (VLC)] in random order,
each for 4 weeks. At baseline and at the end of each treatment period, fasting
samples for fibroblast growth factor (FGF)-21, heme-oxygenase-1 (HO-1), chemerin,
irisin, secreted frizzle-related protein (SFRP-4), total bile acids, ghrelin,
gastrin inhibitory peptide (GIP), peptide-Y, and amylin; hepatic and peripheral
IS; and EE were obtained. Analyses were controlled for age, gender, baseline body
mass index, and diet sequence. RESULTS: FGF-21 decreased (P < 0.0001), with
differential effect by macronutrient composition (mean change from baseline +/-
SEM: LF -49.4 +/- 16.6, LGI -58.6 +/- 16.3, VLC -76.7 +/- 18.2 pg/mL, P =
0.0002). Change in FGF-21 was inversely associated with change in hepatic IS
[Beta = -0.565 units/log(ng/mL), P = 0.02], but not with peripheral IS or EE.
Heme-oxygenase-1 (HO-1) increased (P = 0.003), without differential effect by
macronutrient composition (LF 0.40 +/- 0.26, LGI 0.98 +/- 0.63, VLC 0.49 +/- 0.29
ng/mL, P = 0.07). Ghrelin increased (P = 0.0003), while chemerin decreased (P =
0.001) without macronutrient effect. Total bile acid, irisin, SFRP-4, GIP,
peptide-Y and amylin levels did not change. CONCLUSIONS: FGF-21 levels decreased
with dietary intervention in proportion to carbohydrate content, and correlated
with hepatic insulin sensitivity, suggesting a pattern of improving FGF-21
resistance. HO-1 increased in response to dietary intervention, a tendency to
greater increase in response to the LGI diet. Dietary intervention affected
ghrelin and chemerin, independent of macronutrient composition. These findings
may elucidate relationships between dietary composition, insulin sensitivity and
metabolism. TRIAL REGISTRATION: NCT00315354.
PMID- 28694841
TI - Islam, mental health and law: a general overview.
AB - Islam is the dominant religion in about 56 countries around the globe, and has
more than 1.2 billion followers. Islam represents a holistic way of life, and
according to a large proportion of its followers, the Islamic law or Shari'ah
should prevail over secular law and should be implemented as state law. The
etymological root of the word Shari'ah can be traced back to the harsh life in
the desert and it means "pathway to be followed" or "path to the water hole,"
since the water was the basic element and preserver of life. At the dawn of its
historical course and at its moral and ethical core, Islam introduced many
interesting and innovative beliefs concerning the mentally ill. Islam underlines
the moral necessity for the protection and care of the vulnerable individuals, as
dictated by God himself. On the other hand, beliefs about "possession" and
stigmatization influence the peoples' attitude against and apprehension of mental
disorders. This strange admixture is reflected upon the status of the mental
health services and corresponding legislation found in the different countries of
the Islamic world.
PMID- 28694842
TI - Factors associated with intention to exclusive breastfeed in central women's
hospital, Yangon, Myanmar.
AB - BACKGROUND: Under-nutrition is a public health problem in Myanmar. Despite
current efforts, the exclusive breastfeeding rate (EBF) for children under six
months is only 24%. Intention to breastfeed is a strong predictor for long-term
breastfeeding, however, little is known about pregnant women's breastfeeding
intentions in Myanmar. We, therefore, aimed to identify the factors associated
with women's intention to EBF. METHOD: Data in this article was collected in a
baseline survey for a randomized controlled trial, which aimed to assess the
impact of mobile text messages on the breastfeeding practices of women in Yangon,
Myanmar. A total of 353 pregnant women at 28-34 weeks of gestation, recruited
into the trial from the antenatal clinics of the Central Women's Hospital,
Yangon, Myanmar, responded to the baseline survey questions, which included
background information and breastfeeding related characteristics. To determine
factors associated with women's intention to EBF logistic regression was used to
analyse individual demographic, household economic and breastfeeding
characteristics. In-depth interviews were performed with a sub-sample of 24 women
who participated in the survey, to gain a further understanding of these
associated factors. RESULTS: After adjusting for potential confounders, working
women were less likely to intend to EBF (adjusted odds ratio (AOR) = 0.30, CI
0.17-0.53). Women from rich households (AOR = 2.43, CI 1.08-5.47) and middle
income households (AOR = 1.79, CI 1.01-3.16); those who had high (AOR = 10.19, CI
3.43-30.23) and medium (AOR = 5.46, CI 1.79-16.72) breastfeeding knowledge
levels, and received information from health professionals (AOR = 2.29, CI 1.29
4.03) and mobile internet (AOR 3.62, CI 2.04-6.41) had a higher intention to EBF.
These findings were supported by qualitative analysis, which revealed that
returning to work was the main barrier; health staff and printed media are
reliable sources and; women with higher knowledge had high intentions to EBF.
CONCLUSIONS: EBF intention was influenced by many factors. Breastfeeding
promotion programs should target the poor, working women and women with lower
breastfeeding knowledge. Breastfeeding education via health staff and the
Internet, breastfeeding facilities at the work place and longer maternity leave
in the private sector should all be encouraged. TRIAL REGISTRATION: Australian
New Zealand Clinical Trials Registry ACTRN12615000063516.
PMID- 28694843
TI - Quantifying pruning impacts on olive tree architecture and annual canopy growth
by using UAV-based 3D modelling.
AB - BACKGROUND: Tree pruning is a costly practice with important implications for
crop harvest and nutrition, pest and disease control, soil protection and
irrigation strategies. Investigations on tree pruning usually involve tedious on
ground measurements of the primary tree crown dimensions, which also might
generate inconsistent results due to the irregular geometry of the trees. As an
alternative to intensive field-work, this study shows a innovative procedure
based on combining unmanned aerial vehicle (UAV) technology and advanced object
based image analysis (OBIA) methodology for multi-temporal three-dimensional (3D)
monitoring of hundreds of olive trees that were pruned with three different
strategies (traditional, adapted and mechanical pruning). The UAV images were
collected before pruning, after pruning and a year after pruning, and the impacts
of each pruning treatment on the projected canopy area, tree height and crown
volume of every tree were quantified and analyzed over time. RESULTS: The full
procedure described here automatically identified every olive tree on the orchard
and computed their primary 3D dimensions on the three study dates with high
accuracy in the most cases. Adapted pruning was generally the most aggressive
treatment in terms of the area and volume (the trees decreased by 38.95 and
42.05% on average, respectively), followed by trees under traditional pruning
(33.02 and 35.72% on average, respectively). Regarding the tree heights,
mechanical pruning produced a greater decrease (12.15%), and these values were
minimal for the other two treatments. The tree growth over one year was affected
by the pruning severity and by the type of pruning treatment, i.e., the adapted
pruning trees experienced higher growth than the trees from the other two
treatments when pruning intensity was low (<10%), similar to the traditionally
pruned trees at moderate intensity (10-30%), and lower than the other trees when
the pruning intensity was higher than 30% of the crown volume. CONCLUSIONS:
Combining UAV-based images and an OBIA procedure allowed measuring tree
dimensions and quantifying the impacts of three different pruning treatments on
hundreds of trees with minimal field work. Tree foliage losses and annual canopy
growth showed different trends as affected by the type and severity of the
pruning treatments. Additionally, this technology offers valuable geo-spatial
information for designing site-specific crop management strategies in the context
of precision agriculture, with the consequent economic and environmental
benefits. GRAPHICAL ABSTRACT:
PMID- 28694844
TI - A Synthetic Biology Approach to Engineering Living Photovoltaics.
AB - The ability to electronically interface living cells with electron accepting
scaffolds is crucial for the development of next-generation biophotovoltaic
technologies. Although recent studies have focused on engineering synthetic
interfaces that can maximize electronic communication between the cell and
scaffold, the efficiency of such devices is limited by the low conductivity of
the cell membrane. This review provides a materials science perspective on
applying a complementary, synthetic biology approach to engineering membrane
electrode interfaces. It focuses on the technical challenges behind the
introduction of foreign extracellular electron transfer pathways in bacterial
host cells and the past and future efforts to engineer photosynthetic organisms
with artificial electron-export capabilities for biophotovoltaic applications.
The article highlights advances in engineering protein-based, electron-exporting
conduits in a model host organism, E. coli, before reviewing state-of-the-art
biophotovoltaic technologies that use both unmodified and bioengineered
photosynthetic bacteria with improved electron transport capabilities. A
thermodynamic analysis is used to propose an energetically feasible pathway for
extracellular electron transport in engineered cyanobacteria and identify
metabolic bottlenecks amenable to protein engineering techniques. Based on this
analysis, an engineered photosynthetic organism expressing a foreign, protein
based electron conduit yields a maximum theoretical solar conversion efficiency
of 6-10% without accounting for additional bioengineering optimizations for light
harvesting.
PMID- 28694845
TI - A type-I diacylglycerol acyltransferase modulates triacylglycerol biosynthesis
and fatty acid composition in the oleaginous microalga, Nannochloropsis oceanica.
AB - BACKGROUND: Photosynthetic oleaginous microalgae are considered promising
feedstocks for biofuels. The marine microalga, Nannochloropsis oceanica, has been
attracting ever-increasing interest because of its fast growth, high
triacylglycerol (TAG) content, and available genome sequence and genetic tools.
Diacylglycerol acyltransferase (DGAT) catalyzes the last and committed step of
TAG biosynthesis in the acyl-CoA-dependent pathway. Previous studies have
identified 13 putative DGAT-encoding genes in the genome of N. oceanica, but the
functional role of DGAT genes, especially type-I DGAT (DGAT1), remains ambiguous.
RESULTS: Nannochloropsis oceanica IMET1 possesses two DGAT1 genes: NoDGAT1A and
NoDGAT1B. Functional complementation demonstrated the capability of NoDGAT1A
rather than NoDGAT1B to restore TAG synthesis in a TAG-deficient yeast strain. In
vitro DGAT assays revealed that NoDGAT1A preferred saturated/monounsaturated acyl
CoAs and eukaryotic diacylglycerols (DAGs) for TAG synthesis, while NoDGAT1B had
no detectable enzymatic activity. Assisted with green fluorescence protein (GFP)
fusion, fluorescence microscopy analysis indicated the localization of NoDGAT1A
in the chloroplast endoplasmic reticulum (cER) of N. oceanica. NoDGAT1A knockdown
caused ~25% decline in TAG content upon nitrogen depletion, accompanied by the
reduced C16:0, C18:0, and C18:1 in TAG sn-1/sn-3 positions and C18:1 in the TAG
sn-2 position. NoDGAT1A overexpression, on the other hand, led to ~39% increase
in TAG content upon nitrogen depletion, accompanied by the enhanced C16:0 and
C18:1 in the TAG sn-1/sn-3 positions and C18:1 in the TAG sn-2 position.
Interestingly, NoDGAT1A overexpression also promoted TAG accumulation (by ~2.4
fold) under nitrogen-replete conditions without compromising cell growth, and TAG
yield of the overexpression line reached 0.49 g L-1 at the end of a 10-day batch
culture, 47% greater than that of the control line. CONCLUSIONS: Taken together,
our work demonstrates the functional role of NoDGAT1A and sheds light on the
underlying mechanism for the biosynthesis of various TAG species in N. oceanica.
NoDGAT1A resides likely in cER and prefers to transfer C16 and C18
saturated/monounsaturated fatty acids to eukaryotic DAGs for TAG assembly. This
work also provides insights into the rational genetic engineering of microalgae
by manipulating rate-limiting enzymes such as DGAT to modulate TAG biosynthesis
and fatty acid composition for biofuel production.
PMID- 28694846
TI - Synthetic CO2-fixation enzyme cascades immobilized on self-assembled
nanostructures that enhance CO2/O2 selectivity of RubisCO.
AB - BACKGROUND: With increasing concerns over global warming and depletion of fossil
fuel reserves, it is attractive to develop innovative strategies to assimilate
CO2, a greenhouse gas, into usable organic carbon. Cell-free systems can be
designed to operate as catalytic platforms with enzymes that offer exceptional
selectivity and efficiency, without the need to support ancillary reactions of
metabolic pathways operating in intact cells. Such systems are yet to be
exploited for applications involving CO2 utilization and subsequent conversion to
valuable products, including biofuels. The Calvin-Benson-Bassham (CBB) cycle and
the enzyme ribulose 1,5-bisphosphate carboxylase/oxygenase (RubisCO) play a
pivotal role in global CO2 fixation. RESULTS: We hereby demonstrate the co
assembly of two RubisCO-associated multienzyme cascades with self-assembled
synthetic amphiphilic peptide nanostructures. The immobilized enzyme cascades
sequentially convert either ribose-5-phosphate (R-5-P) or glucose, a simpler
substrate, to ribulose 1,5-bisphosphate (RuBP), the acceptor for incoming CO2 in
the carboxylation reaction catalyzed by RubisCO. Protection from proteolytic
degradation was observed in nanostructures associated with the small dimeric form
of RubisCO and ancillary enzymes. Furthermore, nanostructures associated with a
larger variant of RubisCO resulted in a significant enhancement of the enzyme's
selectivity towards CO2, without adversely affecting the catalytic activity.
CONCLUSIONS: The ability to assemble a cascade of enzymes for CO2 capture using
self-assembling nanostructure scaffolds with functional enhancements show promise
for potentially engineering entire pathways (with RubisCO or other CO2-fixing
enzymes) to redirect carbon from industrial effluents into useful bioproducts.
PMID- 28694847
TI - Arete - candidate gene prioritization using biological network topology with
additional evidence types.
AB - BACKGROUND: Refinement of candidate gene lists to select the most promising
candidates for further experimental verification remains an essential step
between high-throughput exploratory analysis and the discovery of specific causal
genes. Given the qualitative and semantic complexity of biological data,
successfully addressing this challenge requires development of flexible and
interoperable solutions for making the best possible use of the largest possible
fraction of all available data. RESULTS: We have developed an easily accessible
framework that links two established network-based gene prioritization approaches
with a supporting isolation forest-based integrative ranking method. The defining
feature of the method is that both topological information of the biological
networks and additional sources of evidence can be considered at the same time.
The implementation was realized as an app extension for the Cytoscape graph
analysis suite, and therefore can further benefit from the synergy with other
analysis methods available as part of this system. CONCLUSIONS: We provide
efficient reference implementations of two popular gene prioritization algorithms
- DIAMOnD and random walk with restart for the Cytoscape system. An extension of
those methods was also developed that allows outputs of these algorithms to be
combined with additional data. To demonstrate the utility of our software, we
present two example disease gene prioritization application cases and show how
our tool can be used to evaluate these different approaches.
PMID- 28694848
TI - epiACO - a method for identifying epistasis based on ant Colony optimization
algorithm.
AB - BACKGROUND: Identifying epistasis or epistatic interactions, which refer to
nonlinear interaction effects of single nucleotide polymorphisms (SNPs), is
essential to understand disease susceptibility and to detect genetic
architectures underlying complex diseases. Though many works have been done for
identifying epistatic interactions, due to their methodological and computational
challenges, the algorithmic development is still ongoing. RESULTS: In this study,
a method epiACO is proposed to identify epistatic interactions, which based on
ant colony optimization algorithm. Highlights of epiACO are the introduced
fitness function Svalue, path selection strategies, and a memory based strategy.
The Svalue leverages the advantages of both mutual information and Bayesian
network to effectively and efficiently measure associations between SNP
combinations and the phenotype. Two path selection strategies, i.e.,
probabilistic path selection strategy and stochastic path selection strategy, are
provided to adaptively guide ant behaviors of exploration and exploitation. The
memory based strategy is designed to retain candidate solutions found in the
previous iterations, and compare them to solutions of the current iteration to
generate new candidate solutions, yielding a more accurate way for identifying
epistasis. CONCLUSIONS: Experiments of epiACO and its comparison with other
recent methods epiMODE, TEAM, BOOST, SNPRuler, AntEpiSeeker, AntMiner, MACOED,
and IACO are performed on both simulation data sets and a real data set of age
related macular degeneration. Results show that epiACO is promising in
identifying epistasis and might be an alternative to existing methods.
PMID- 28694849
TI - Optimisation of rocker sole footwear for prevention of first plantar ulcer:
comparison of group-optimised and individually-selected footwear designs.
AB - BACKGROUND: Appropriate footwear for individuals with diabetes but no ulceration
history could reduce the risk of first ulceration. However, individuals who deem
themselves at low risk are unlikely to seek out bespoke footwear which is
personalised. Therefore, our primary aim was to investigate whether group
optimised footwear designs, which could be prefabricated and delivered in a
retail setting, could achieve appropriate pressure reduction, or whether footwear
selection must be on a patient-by-patient basis. A second aim was to compare
responses to footwear design between healthy participants and people with
diabetes in order to understand the transferability of previous footwear
research, performed in healthy populations. METHODS: Plantar pressures were
recorded from 102 individuals with diabetes, considered at low risk of
ulceration. This cohort included 17 individuals with peripheral neuropathy. We
also collected data from 66 healthy controls. Each participant walked in 8 rocker
shoe designs (4 apex positions * 2 rocker angles). ANOVA analysis was then used
to understand the effect of two design features and descriptive statistics used
to identify the group-optimised design. Using 200 kPa as a target, this group
optimised design was then compared to the design identified as the best for each
participant (using plantar pressure data). RESULTS: Peak plantar pressure
increased significantly as apex position was moved distally and rocker angle
reduced (p < 0.001). The group-optimised design incorporated an apex at 52% of
shoe length, a 20 degrees rocker angle and an apex angle of 95 degrees . With
this design 71-81% of peak pressures were below the 200 kPa threshold, both in
the full cohort of individuals with diabetes and also in the neuropathic
subgroup. Importantly, only small increases (<5%) in this proportion were
observed when participants wore footwear which was individually selected. In
terms of optimised footwear designs, healthy participants demonstrated the same
response as participants with diabetes, despite having lower plantar pressures.
CONCLUSIONS: This is the first study demonstrating that a group-optimised,
generic rocker shoe might perform almost as well as footwear selected on a
patient by patient basis in a low risk patient group. This work provides a
starting point for clinical evaluation of generic versus personalised pressure
reducing footwear.
PMID- 28694850
TI - Heart Team: who is The Captain?
PMID- 28694851
TI - Comparison Between Alprostadil and Iloprost in Intravenous Treatment of Patients
With Chronic Peripheral Arterial Disease.
AB - INTRODUCTION: chronic peripheral arterial disease (PAD) seems to be a
"rediscovered" pathology nowadays, brought into spotlight by its strong
correlation with other signifi cant cardiovascular disorders. OBJECTIVES: to
sustain a real benefi t from treatment with i.v. prostaglandins (PG) in PAD
patients and to directly compare the currently used PG: alprostadil and iloprost.
METHOD: open, non-randomized cohort study, with placebo group ("classical
therapy") reviewing 615 PAD patients with therapeutic approach during 2003-2012
period, divided in 3 subgroups: "classical" therapy; "classical" therapy +
iloprost; "classical" therapy + alprostadil; patients with Burger's disease were
excluded; multiple factor analysis with statistical results inserted. RESULTS:
clear domination of male gender patients, with older female gender patients
(p.0.001); smoking like major risk factor in male and in all patients (p<
0.0001); 124 patients underwent angiography . CONCLUSION: a real improvement in
the clinical status of patients receiving i.v. prostaglandin therapy with no diff
erences between genders, diabetic and non-diabetic patients; alprostadil seems
better than iloprost.
PMID- 28694852
TI - Does the Genetic Cause of Prader-Willi Syndrome Explain the Highly Variable
Phenotype?
AB - INTRODUCTION: Prader-Willi syndrome (PWS) is characterized by extensive clinical
and genetic variability caused by lack of expression of imprinted genes of the
chromosomal region 15q11.2-q13. The genotye-phenotype correlation has not been
yet fully elucidated. AIM: To analyze these correlations in order to determine
the role of specifi c geneic alterations in the development of clinical symptoms
in PWS. MATERIAL AND METHOD: We retrospectively analyzed data routinely collected
as part of the clinical care of 52 patients with clinical suspicion of PWS. FISH
test was performed in all patients; in case of negative results, methylation test
was performed. RESULT: PWS was confi rmed in 35 patients that were divided in two
groups according to the genetic cause of PWS: group A-21 patients with 15q11-q13
region deletion, mean age at evaluation 8.1 years (SD= 5.6) and mean of clinical
score 9.4 +/- 1.8; group B-14 patients with positive methylation test, with mean
age at evaluation 6.7 years (SD= 4.6) and mean of clinical score 10.1 +/- 1.9.
Facial dysmorphism and neonatal hypotonia were present in all evaluated patients;
while, higher frequency of major and minor PWS criteria were noted in the group
A. Onset of hyperphagia, was around the age of 2 years in most patients, however
one patient from group B had normal eating behavior and normal weight beyond age
5 years. CONCLUSION: In our study, the various genotypes did not seem to explain
the diff erence in phenotype in PWS patients. We found a delayed time until
diagnosis in these patients, although all had neonatal hypotonia and other
suggestive phenotypic features, underlining once more the need for increased
awareness of this syndrome, as well as easier accessibility to genetic
counseling.
PMID- 28694853
TI - Evaluation of Hyoid Position in Children of 7-11 Years Old with Ankyloglossia in
Lateral Cephalometic Radiographs.
AB - INTRODUCTION: Ankyloglossia is an anatomic developmental anomaly determining by
thick and short, fi brotic ferenum. Tongue changes have severe eff ects on
occlusion and oropharyngeal structures. The aim of this study was to evaluate the
position of hyoid in children 7-11 years' old with ankyloglossia in lateral
cephalometric radiographs. MATERIAL AND METHOD: 30 radiographs of children with
ankyloglossia with mean age of 9.8 and 30 radiographs of control group were
chosen and matched in terms of age, sex, class of malocclusion and growth
pattern. The measurements of hyoid position were done (C3-RGN, C3-H, H-RGN, HP)
and analyzed with paired t-test under SPSS-15 software. RESULT: The means of C3
RGN, C3-H, H-RGN, HP were 66.2, 30.9, 33.4, 3.2 and 7.45, 36.8, 34.1, 68.6 in
ankyloglossia and control groups respectively. Lower amount of measurements were
statistically signifi cant (p-value<0.05). CONCLUSION: Size and position of hyoid
in children with ankyloglossia show more posterior- superior Position than
healthy children.
PMID- 28694854
TI - Antimicrobial Resistant Pattern and Capsular Typing of Streptococcus Pneumoniae
Isolated from Children in Sistan -Baluchestan.
AB - BACKGROUND: Ankyloglossia is an anatomic developmental anomaly determining by
thick and short, fi brotic ferenum. Tongue changes have severe eff ects on
occlusion and oropharyngeal structures. The aim of this study was to evaluate the
position of hyoid in children 7-11 years' old with ankyloglossia in lateral
cephalometric radiographs. MATERIALS AND METHOD: In this study 260 nasopharyngeal
swabs were taken from non-vaccinated healthy children between 6 months to 6 years
old at medical centers in Sistan-Baluchestan during August 2013 to January 2014.
These samples were cultured on blood agar. Primary identifi cation of bacterial
isolated was determined by biochemical analysis and molecular tests. Capsular
typing was performed by Multiplex PCR using primers targeting cps locus that is
highly conserved among diff erent capsular types. The master mixes for PCR were
grouped them into six multiplex reactions. RESULTS: Out of 260 nasopharyngeal
swabs, 42 isolates of Streptococcus pneumoniae were detected and identifi ed. The
overall pneumococcal carriage rate was 16.1%. The most frequently isolated
capsular types were: 6A/B, 19A, 19F and 23F. These capsular types accounted for
49.9% of all strains detected. CONCLUSION: We found that the prevalence of
pneumococcal carriage among non-vaccinated children under six years old is about
16%. Our study provides much data about carriage rate and pneumococcal capsular
types in preschool children, which is necessary for predicting the diff erent
valent pneumococcal conjugated vaccines in Iran.
PMID- 28694855
TI - The Effects of Sweet, Bitter, Salty and Sour Stimuli on Alpha Rhythm. A Meg
Study.
AB - OBJECTIVE: the possible diff erences in processing gustatory stimuli in healthy
subjects was investigated by magnetoencephalography (meg). MATHERIAL AND METHOD:
meg recordings were evaluated for 10 healthy volunteers (3 men within the age
range 20-46 years, 7 women within the age range 10-28 years), with four diff
erent gustatory stimuli: sweet, bi" er, sour and salty. Fast fourier transform
was performed on meg epochs recorded for the above conditions and the eff ect of
each kind of stimuli on alpha rhythm was examined. OUTCOMES: A significant higher
percent of alpha power was found irrespective of hemispheric side in all
gustatory states located mainly at the occipital, le$ and right parietal lobes.
One female volunteer experienced no statistically signifi cance when comparing
normal with salty and sour taste respectively. Two female volunteers exhibited no
statistically signifi cance when comparing their normal with their salty taste.
One male volunteer experienced no statistically signifi cance when comparing the
normalbitter and normal-salty states correspondingly. All the other subjects
showed statistically signifi cant changes in alpha power for the 4 gustatory
stimuli. CONCLUSION: The pattern of activation caused by the four stimuli
indicated elevated gustatory processing mechanisms. This cortical activation
might have applicability in modulation of brain status.
PMID- 28694856
TI - Social Determinant Factors and their Relationship with Nutritional Pattern in
Cardiovascular Patients after Hospital Discharge.
AB - INTRODUCTION: Several evidences suggest that it will be possible to reduce the
risk of cardiovascular diseases by modifying its risk factors. Current study
designed for identifying some social determinant factors and their relationship
with nutritional pa! ern in cardiovascular patients a" er hospital discharge.
METHODS: This cross-sectional study was conducted on 385 cardiovascular
discharged patients from an university specialized heart educational hospital.
Patients were included by simple sampling methods. Data collected via interview
and a preset questionnaire with two diff erent sections; demographic and
nutrition evaluation section one. Collected data was analyzed by SPSS 20
software. RESULTS: The results showed a signifi cant relationship between
nutritional pa! erns and age, location, job, marital and educational status.
There was no signifi cant relationship between nutritional pa! ern and sex,
income, and housekeeping status. CONCLUSION: Some social factors are eff ective
on nutritional pa! ern in patients with cardiovascular diseases that they can be
used in diff erent fi elds for investment, including nursing education and
management services.
PMID- 28694857
TI - Managing Crohn's Disease during Pregnancy.
AB - Crohn's disease (CD) is a chronic infl ammatory bowel disease with onset during
reproductive age. Advancement in medical therapies and treatment strategies have
made pregnancy following a diagnosis of CD a viable and safe option for more
women with this disease. In this review we discuss the evidence based management
of Crohn's disease during pregnancy.
PMID- 28694858
TI - Local Application of Vibration in Motor Rehabilitation - Scientific and Practical
Considerations.
AB - Vibration stimulates specific receptors, cutaneous and musculo-tendinous. The aff
erent impulses travel through spinal neurons to thalamus and cortical structures.
The local muscular response to a vibration is a tonic vibratory refl ex. This
refl ex depends on many factors: frequency, amplitude, and tendon and muscle
length. Based upon this refl ex, vibration produced alteration of isometric and
isotonic contraction, fl exibility, spasticity. Many studies investigated
facilitator eff ects on movement in stroke patients and spinal cord injuries.
There is further need to set the place of vibration in the therapeutic fi eld of
motor control enhancement.
PMID- 28694859
TI - Interplay Between Prolactin and Pathogenesis of Psoriasis Vulgaris.
AB - INTRODUCTION: The polypeptide hormone prolactin (PRL) represents the pituitary
modulator of lactation and reproduction. Currently, we discuss the wide range of
PRL actions "beyond the mammary horizon". Multiple studies had showed the role of
PRL as a cytokine, with comparable structural motifs, similar receptor structures
and signal transduction pathways. Almost two decades ago it was fi rst
hypothesized that PRL acts as a neuroendocrine modulator of both skin epithelial
growth and the skin immune system. Moreover, it was described the PRL circuit
between the skin and the central nervous system. Psoriasis vulgaris, an
immunologically mediated skin disease, is a common disorder, having as main
pathogenetic mechanisms the chronic infl ammation and keratinocytes
hyperproliferation. Psoriasis vulgaris is not a life threatening disease, but aff
ects seriously the quality of life; there is still no causative treatment.
METHODS: After we describe the essentials of general PRL biology, the almost
ubiquitous distribution of its receptors and the vast list of extrapituitary PRL
expressing tissues, our aim is to summarize clinical observations that provide
insights into how PRL may impact on the psoriatic skin and defi ne research for
be% er characterize the complex role of PRL in human skin biology and pathology.
RESULTS: Focusing on psoriasis, as a stress-related disease, we then discuss the
possible role of PRL/ PRLR in its pathology and may identify one potential
biological marker and therapeutic targets for the management of this autoimmune
skin disorder. CONCLUSION: This theory/concept can now be integrated into current
views on the multilevel neuroendocrine- immune communication along the brain-skin
axis in health and disease. Due to the pathogenic complexity, there is no
curative treatment for psoriasis and pharmacological modulation of PRL may
represent a future target to restrict the lesions in psoriatic patients.
PMID- 28694860
TI - Postpartum Aortic Bifurcation Thrombosis on the Background of Thrombophilic
Disorder.
AB - Two main causes of arterial thrombosis are known: fi rst - atherosclerosis,
extensively studied, and the second - atrial fi brillation. The lack of any risk
factors and the occurrence at young age of a thrombotic event requires us to
investigate possible other conditions, including inherited thrombophilia that is
represented by a series of genetic disorders that increase the risk of
thromboembolic disease. The role of thrombophilia in the occurrence of arterial
thrombosis is inconsequential; this disorder is characterized by the tendency of
developing venous thrombosis. We present a rare case of a 29 year old woman that
presents an arterial thrombotic event subsequent to the caesarean section. The
patient had a positive familial history for thrombotic events and a cavernous
sinus thrombosis in personal history. Prophylactic treatment with unfractionated
heparin throughout pregnancy was applied. At 31 weeks gestation the patient
underwent cesarean surgery for nonreassuring fetal status, 2 weeks fetal
intrauterine growth restriction and absent diastolic fl ow of uterine arteries.
Three days post operatory arterial thrombosis is suspected. The context that led
to this suspicion was paresthesia, color modifi cation of the right leg and
abolished popliteal pulse. Angiographic-CT confi rmed the presumptive diagnosis.
A cardiovascular, conservatory treatment was successfully applied. Considering
the particularities of the presented case we discuss the occurrence of arterial
thrombosis postpartum in the context of confi rmed thrombophilia by reviewing the
specialized literature.
PMID- 28694861
TI - An Uncommon Cause of Longitudinally Extensive Transverse Myelitis.
AB - Considering that currently Romania has the highest tuberculosis incidence in
Europe, the recognition of the infection is an acknowledged health issue. Central
nervous system tuberculosis accounts for approximately 1% of all cases of
tuberculosis. Longitudinally extensive transverse myelitis is a contiguous infl
ammatory lesion of the spinal cord which involves three or more spinal segments.
In tuberculosis, spinal cord involvement is rare and is usually rather due to
radiculomyelitis or spinal tuberculoma, and only very rare due to longitudinally
extensive transverse myelitis. We present the case of a 52-year-old man referred
to our department for progressive neurological deficits due to a longitudinally
extensive transverse myelitis. After a thorough work-up we diagnosed the patient
with longitudinally extensive transverse myelitis secondary to infection with
Mycobacterium tuberculosis.
PMID- 28694862
TI - Primary Hepatic Marginal Zone Lymphoma in a Patient with Chronic Hepatitis C.
AB - Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) is
a low-grade malignant lymphoma that appears frequently in the stomach, but other
sites can also be involved: the intestinal tract, lungs, head, neck, skin,
thyroid, breasts and liver. Recently, epidemiological evidences support the idea
that there is an association between hepatitis C and B-cell non-Hodgkin lymphomas
(that include MALT as a subtype). Primary non-Hodgkin lymphomas confi ned only to
the liver are very rare (only 0.016% of all cases of all non-Hodgkin's lymphomas)
and MALT is not the most frequent type. We present the case of a male patient,
age 62, known with chronic hepatitis C, previously relapser a" er a 72 week
treatment with peg-interferon alfa and ribavirin that was diagnosed at three
years a" er the relapse with multiple focal liver lesions. One of the tumors was
surgically removed and the histological exam performed demonstrated an extranodal
marginal zone lymphoma with small B-cell with plasmacytoid diff erentiation confi
ned only to the liver. Direct acting antiviral (DAA) therapy was started, but the
virologic clearance was not obtained by week 10, leading to a change of DAA
regimen at week 12. The antiviral therapy was continued until week 24. Imaging
showed an increase in number and size of the focal lesions until week 12. At week
12 chemo- and immune-therapy was started with bendamustine and rituximab. A"
erwards the evolution was favorable, the patient being now in complete remission
and with undetectable viral load.
PMID- 28694863
TI - Kinetic analysis of mechanoradical formation during the mechanolysis of dextran
and glycogen.
AB - A detailed electron spin resonance (ESR) analysis of mechanically induced free
radicals (mechanoradicals) formation of glucose-based polysaccharides, dextran
(Dx) and glycogen (Gly) was performed in comparison with amylose mechanoradicals.
The ESR spectra of the samples mechanically fractured at room temperature were
multicomponent. The radical concentration of Dx and Gly mechanoradicals gradually
decreased during vibratory milling after reaching the maximum value. Although the
molecular weight of Dx or the particle diameter of Gly steeply diminished until
reaching the each maximum value of radical concentration, after that the
molecular weight or the particle diameter slowly decreased. These results
suggested that Dx and Gly mechanoradicals might be more unstable than amylose
radicals possessing an intramolecular helical structure due to the branched
structure.
PMID- 28694864
TI - Phosphorus pentasulfide mediated conversion of organic thiocyanates to thiols.
AB - In this paper we report an efficient and mild procedure for the conversion of
organic thiocyanates to thiols in the presence of phosphorus pentasulfide (P2S5)
in refluxing toluene. The method avoids the use of expensive and hazardous
transition metals and harsh reducing agents, as required by reported methods, and
provides an attractive alternative to the existing methods for the conversion of
organic thiocyanates to thiols.
PMID- 28694865
TI - Towards open-ended evolution in self-replicating molecular systems.
AB - In this review we discuss systems of self-replicating molecules in the context of
the origin of life and the synthesis of de novo life. One of the important
aspects of life is the ability to reproduce and evolve continuously. In this
review we consider some of the prerequisites for obtaining unbounded evolution of
self-replicating molecules and describe some recent advances in this field. While
evolution experiments involving self-replicating molecules have shown promising
results, true open-ended evolution has not been realized so far. A full
understanding of the requirements for open-ended evolution would provide a better
understanding of how life could have emerged from molecular building blocks and
what is needed to create a minimal form of life in the laboratory.
PMID- 28694866
TI - Strategies in megasynthase engineering - fatty acid synthases (FAS) as model
proteins.
AB - Megasynthases are large multienzyme proteins that produce a plethora of important
natural compounds by catalyzing the successive condensation and modification of
precursor units. Within the class of megasynthases, polyketide synthases (PKS)
are responsible for the production of a large spectrum of bioactive polyketides
(PK), which have frequently found their way into therapeutic applications.
Rational engineering approaches have been performed during the last 25 years that
seek to employ the "assembly-line synthetic concept" of megasynthases in order to
deliver new bioactive compounds. Here, we highlight PKS engineering strategies in
the light of the newly emerging structural information on megasynthases, and
argue that fatty acid synthases (FAS) are and will be valuable objects for
further developing this field.
PMID- 28694867
TI - Sugar-based micro/mesoporous hypercross-linked polymers with in situ embedded
silver nanoparticles for catalytic reduction.
AB - Porous hypercross-linked polymers based on perbenzylated monosugars (SugPOP-1-3)
have been synthesized by Friedel-Crafts reaction using formaldehyde dimethyl
acetal as an external cross-linker. Three perbenzylated monosugars with similar
chemical structure were used as monomers in order to tune the porosity. These
obtained polymers exhibit microporous and mesoporous features. The highest
Brunauer-Emmett-Teller specific surface area for the resulting polymers was found
to be 1220 m2 g-1, and the related carbon dioxide storage capacity was found to
be 14.4 wt % at 1.0 bar and 273 K. As the prepared porous polymer SugPOP-1 is
based on hemiacetal glucose, Ag nanoparticles (AgNPs) can be successfully
incorporated into the polymer by an in situ chemical reduction of freshly
prepared Tollens' reagent. The obtained AgNPs/SugPOP-1 composite demonstrates
good catalytic activity in the reduction of 4-nitrophenol (4-NP) with an activity
factor ka = 51.4 s-1 g-1, which is higher than some reported AgNP-containing
composite materials.
PMID- 28694868
TI - Aqueous semisynthesis of C-glycoside glycamines from agarose.
AB - Agarose was herein employed as starting material to produce primary, secondary
and tertiary C-glycoside glycamines, including mono- and disaccharide structures.
The semisynthetic approach utilized was generally based on polysaccharide
controlled hydrolysis followed by reductive amination. All reactions were
conducted in aqueous media and without the need of hydroxyl group protection. We
were able to identify optimal conditions for the reductive amination of agar
hydrolysis products and to overcome the major difficulties related to this kind
of reaction, also extending it to reducing anhydrosugars. The excess of ammonium
acetate, methyl- or dimethylamine, and the use of a diluted basic (pH 11)
reaction media were identified as important aspects to achieve improved yields,
as well as to decrease the amount of byproducts commonly related to reductive
amination of carbohydrates. This strategy allowed the transposition of the 3,6
anhydro-alpha-L-galactopyranose unit (naturally present in the agarose structure)
to all glycamines synthesized, constituting an amino-substituted C
threofuranoside moiety, which is closely related to (+)-muscarine.
PMID- 28694869
TI - Synthesis of alkynyl-substituted camphor derivatives and their use in the
preparation of paclitaxel-related compounds.
AB - Compounds containing two alkyne groups in close vicinity at the rigid skeleton of
camphorsulfonamide show unique reactivities when treated with electrophiles or
catalytic amounts of platinum(II). The formed product structures depend not only
on the reagents used but also on the substituents attached to the triple bonds.
Cycloisomerisations with perfect atom economy lead to polycyclic heterocycles
that resemble to some extent the AB ring system of paclitaxel. Herein, we present
practical synthetic methods for the selective synthesis of precursor dialkynes
bearing different substituents (alkyl, aryl) at the triple bonds, based on ketals
or an imine as protecting groups. We show for isomeric dialkynes that the
reaction cascade induced by Pt(II) includes ring annulation, sulphur reduction,
and ring enlargement. One isomeric dialkyne additionally allows for the isolation
of a pentacyclic compound lacking the ring enlargement step, which we have
proposed as a potential intermediate in the catalytic cycle.
PMID- 28694870
TI - Strategies toward protecting group-free glycosylation through selective
activation of the anomeric center.
AB - Glycosylation is an immensely important biological process and one that is highly
controlled and very efficient in nature. However, in a chemical laboratory the
process is much more challenging and usually requires the extensive use of
protecting groups to squelch reactivity at undesired reactive moieties.
Nonetheless, by taking advantage of the differential reactivity of the anomeric
center, a selective activation at this position is possible. As a result,
protecting group-free strategies to effect glycosylations are available thanks to
the tremendous efforts of many research groups. In this review, we showcase the
methods available for the selective activation of the anomeric center on the
glycosyl donor and the mechanisms by which the glycosylation reactions take place
to illustrate the power these techniques.
PMID- 28694871
TI - Total synthesis of elansolids B1 and B2.
AB - The elansolids A1-A3, B1, and B2 are secondary metabolites formed by the gliding
bacterium Chitinophaga sancti. They show antibacterial activity against Gram
positive bacteria. A second generation total synthesis of the antibiotic
elansolid B1 (2) and the first synthesis of elansolid B2 (3) are reported. In
contrast to previous work, the (Z,E,Z)-triene at C10-C15 was assembled by using
an optimized C-C cross-coupling sequence with a Suzuki cross-coupling reaction as
key step.
PMID- 28694872
TI - Biomimetic molecular design tools that learn, evolve, and adapt.
AB - A dominant hallmark of living systems is their ability to adapt to changes in the
environment by learning and evolving. Nature does this so superbly that intensive
research efforts are now attempting to mimic biological processes. Initially this
biomimicry involved developing synthetic methods to generate complex bioactive
natural products. Recent work is attempting to understand how molecular machines
operate so their principles can be copied, and learning how to employ biomimetic
evolution and learning methods to solve complex problems in science, medicine and
engineering. Automation, robotics, artificial intelligence, and evolutionary
algorithms are now converging to generate what might broadly be called in silico
based adaptive evolution of materials. These methods are being applied to organic
chemistry to systematize reactions, create synthesis robots to carry out unit
operations, and to devise closed loop flow self-optimizing chemical synthesis
systems. Most scientific innovations and technologies pass through the well-known
"S curve", with slow beginning, an almost exponential growth in capability, and a
stable applications period. Adaptive, evolving, machine learning-based molecular
design and optimization methods are approaching the period of very rapid growth
and their impact is already being described as potentially disruptive. This paper
describes new developments in biomimetic adaptive, evolving, learning
computational molecular design methods and their potential impacts in chemistry,
engineering, and medicine.
PMID- 28694873
TI - Synthesis of novel 13alpha-estrone derivatives by Sonogashira coupling as
potential 17beta-HSD1 inhibitors.
AB - Novel 13alpha-estrone derivatives were synthesized by Sonogashira coupling.
Transformations of 2- or 4-iodo regioisomers of 13alpha-estrone and its 3-methyl
ether were carried out under different conditions in a microwave reactor. The 2
iodo isomers were reacted with para-substituted phenylacetylenes using Pd(PPh3)4
as catalyst and CuI as a cocatalyst. Coupling reactions of 4-iodo derivatives
could be achieved by changing the catalyst to Pd(PPh3)2Cl2. The product
phenethynyl derivatives were partially or fully saturated. Compounds bearing a
phenolic OH group furnished benzofurans under the conditions used for the partial
saturation. The inhibitory effects of the compounds on human placental 17beta
hydroxysteroid dehydrogenase type 1 isozyme (17beta-HSD1) were investigated by an
in vitro radiosubstrate incubation method. Certain 3-hydroxy-2-phenethynyl or
phenethyl derivatives proved to be potent 17beta-HSD1 inhibitors, displaying
submicromolar IC50 values.
PMID- 28694874
TI - Milk exosomes: beyond dietary microRNAs.
AB - Extracellular vesicles deliver a variety of cargos to recipient cells, including
the delivery of cargos in dietary vesicles from bovine milk to non-bovine
species. The rate of discovery in this important line of research is slowed by a
controversy whether the delivery and bioactivity of a single class of vesicle
cargos, microRNAs, are real or not. This opinion paper argues that the evidence
in support of the bioavailability of microRNAs encapsulated in dietary exosomes
outweighs the evidence produced by scholars doubting that phenomenon is real.
Importantly, this paper posits that the time is ripe to look beyond microRNA
cargos and pursue innovative pathways through which dietary exosomes alter
metabolism. Here, we highlight potentially fruitful lines of exploration.
PMID- 28694875
TI - Diet-derived microRNAs: unicorn or silver bullet?
AB - In ancient lore, a bullet cast from silver is the only effective weapon against
monsters. The uptake of active diet-derived microRNAs (miRNAs) in consumers may
be the silver bullet long sought after in nutrition and oral therapeutics.
However, the majority of scientists consider the transfer and regulation of
consumer's gene activity by these diet-derived miRNAs to be a fantasy akin to
spotting a unicorn. Nevertheless, groups like Dr. Chen-Yu Zhang's lab in Nanjing
University have stockpiled breathtaking amounts of data to shoot down these
naysayers. Meanwhile, Dr. Ken Witwer at John Hopkins has steadfastly cautioned
the field to beware of fallacies caused by contamination, technical artifacts,
and confirmation bias. Here, Dr. Witwer and Dr. Zhang share their realities of
dietary miRNAs by answering five questions related to this controversial field.
PMID- 28694876
TI - Navigating dietary small RNAs.
AB - When a novel nutritional concept comes along, scientists become enthusiastic and
start new explorations. In 2012, the field was enthralled with a study suggesting
plant-based nucleic acid "information" acts as a bioactive to regulate animal
metabolism.
PMID- 28694878
TI - ROC Curve Analysis in the Presence of Imperfect Reference Standards.
AB - The receiver operating characteristic (ROC) curve is an important tool for the
evaluation and comparison of predictive models when the outcome is binary. If the
class membership of the outcomes are known, ROC can be constructed for a model,
and the ROC with greater area under the curve (AUC) indicates better performance.
However in practice, imperfect reference standards often exist, in which class
membership of every data point are not fully determined. This situation is
especially prevalent in high-throughput biomedical data because obtaining perfect
reference standards for all data points is either too costly or technically
impractical. To construct ROC curves for these data, the common practice is to
either ignore the uncertainties in references, or remove data points with high
uncertainties. Such approaches may cause bias to the ROC curves and generate
misleading results in method evaluation. Here we present a framework to
incorporate membership uncertainties into the construction of ROC curve, termed
the expected ROC or "eROC" curve. We develop an efficient procedure for the
estimation of eROC curve. The advantages of using eROC are demonstrated using
simulated and real data.
PMID- 28694877
TI - Attention deficit hyperactivity disorder (ADHD) in phenotypically similar
neurogenetic conditions: Turner syndrome and the RASopathies.
AB - BACKGROUND: ADHD (attention deficit hyperactivity disorder) is a common
neurodevelopmental disorder. There has been extensive clinical and basic research
in the field of ADHD over the past 20 years, but the mechanisms underlying ADHD
risk are multifactorial, complex and heterogeneous and, as yet, are poorly
defined. In this review, we argue that one approach to address this challenge is
to study well-defined disorders to provide insights into potential biological
pathways that may be involved in idiopathic ADHD. MAIN BODY: To address this
premise, we selected two neurogenetic conditions that are associated with
significantly increased ADHD risk: Turner syndrome and the RASopathies (of which
Noonan syndrome and neurofibromatosis type 1 are the best-defined with regard to
ADHD-related phenotypes). These syndromes were chosen for two main reasons:
first, because intellectual functioning is relatively preserved, and second,
because they are strikingly phenotypically similar but are etiologically
distinct. We review the cognitive, behavioural, neural and cellular phenotypes
associated with these conditions and examine their relevance as a model for
idiopathic ADHD. CONCLUSION: We conclude by discussing current and future
opportunities in the clinical and basic research of these conditions, which, in
turn, may shed light upon the biological pathways underlying idiopathic ADHD.
PMID- 28694879
TI - Estimating a Treatment Effect in Residual Time Quantiles under the Additive
Hazards Model.
AB - For randomized clinical trials where the endpoint of interest is a time-to-event
subject to censoring, estimating the treatment effect has mostly focused on the
hazard ratio from the Cox proportional hazards model. Since the model's
proportional hazards assumption is not always satisfied, a useful alternative,
the so-called additive hazards model, may instead be used to estimate a treatment
effect on the difference of hazard functions. Still, the hazards difference may
be difficult to grasp intuitively, particularly in a clinical setting of, e.g.,
patient counseling, or resource planning. In this paper, we study the quantiles
of a covariate's conditional survival function in the additive hazards model.
Specifically, we estimate the residual time quantiles, i.e., the quantiles of
survival times remaining at a given time t, conditional on the survival times
greater than t, for a specific covariate in the additive hazards model. We use
the estimates to translates the hazards difference into the difference in
residual time quantiles, which allows a more direct clinical interpretation. We
determine the asymptotic properties, assess the performance via Monte-Carlo
simulations, and demonstrate the use of residual time quantiles in two real
randomized clinical trials.
PMID- 28694880
TI - Alzheimer's Disease and Paraoxonase 1 (PON1) Gene Polymorphisms.
AB - BACKGROUND: Some studies have indicated that human paraoxonase 1 (PON1) activity
shows a polymorphic distribution. The aim of this study was to determine the
distribution of PON1 polymorphism in patients with Alzheimer's disease in Gorgan
and compare it with a healthy control group. METHOD: The study included 100
healthy individuals and 50 patients. Enzyme activity and genetic polymorphism of
PON1 were determined. RESULT: There were significant differences in distribution
of genotypes and alleles among patients and control group. The most common
genotype was CT in patients and control group, while the most frequent alleles
were T and C in patients and controls, respectively. There was a statistically
significant variation between serum PON1 activity and -108C> T polymorphism. The
highest PON1 enzyme activities in the patients and controls were found in CC,
while lower enzyme activities were seen in CT and TT genotypes in both genders
and age groups. CONCLUSION: Onset of Alzheimer's disease may depend on different
polymorphisms of the PON1 enzyme. Late or early-onset of Alzheimer's disease may
also depend on age and gender distribution, especially for arylesterase enzyme.
Further studies on polymorphism of the enzyme are necessary for interpretation of
possible polymorphic effects of enzyme on PON1 activity in humans.
PMID- 28694881
TI - Evaluation of a Probe-Based PCR-ELISA System for Simultaneous Semi Quantitative
Detection and Genotyping of Human Cytomegalovirus (HCMV) Infection in Clinical
Specimens.
AB - BACKGROUND: Human cytomegalovirus (HCMV) is a common opportunistic pathogen that
causes serious complications in immunosuppressed patients and infected newborns.
In this study, PCR-ELISA was optimized for semi-quantitative detection of
infection in clinical specimens and simultaneous genotyping of glycoprotein B for
4 major genotypes, due to its significance. METHOD: During DIG-labeling PCR, a
pair of primers amplifies a fragment of variable region of the glycoprotein B
encoding sequence. Under optimized conditions, labeled Target amplicons hybridize
to biotinated specific probes and are detected in an ELISA system. RESULTS: PCR
ELISA system showed specific performance with detection limit of approximately
100 copies of CMV DNA. The linear correlation was observed between the PCR-ELISA
results (OD) and logarithmic scale of CMV (r=0.979). Repeatability of PCR-ELISA
detection system for intra-assay and inter-assay was evaluated for negative and
positive samples. In optimized conditions of hybridization, differentiation
between genotypes of glycoprotein B was feasible using genotype-specific probes
in PCR-ELISA genotyping system. In comparison with sequencing method, genotyping
system was confirmed with kappa index of 1. CONCLUSION: PCR-ELISA is proposed as
an applicable and reliable technique for semi-quantitative diagnosis and typing
of the infection. This technique is flexible to apply in a variety of molecular
fields.
PMID- 28694882
TI - Risk Factors for Acquisition of Fluoroquinolone or Aminoglycoside Resistance in
Addition to Carbapenem Resistance in Pseudomonas Aeruginosa.
AB - BACKGROUND: Carbapenems, fluoroquinolones (FQs), and aminoglycosides (AGs) are
key drugs for treating Pseudomonas aeruginosa infections, and accumulation of
drug resistances make antibiotic therapy difficult. METHODS: We evaluated 169
patients with imipenem (IPM)-resistant P. aeruginosa and compared patient
background and microbiological characteristics between groups with or without FQ
resistance. Similar analyses were performed for AG. RESULTS: Of the 169 IPM
resistant strains, 39.1% showed resistance to FQs and 7.1% to AGs. The frequency
of exposure to FQs within 90 days previously was higher in the group with FQ
resistance (45.5%) than in the group without FQ resistance (13.6%). Similarly,
33.3% of patients in the group with AG resistance had been previously
administered AGs, higher than the 7.6% of patients without AG resistance.
Frequencies of metallo-beta-lactamase (MBL) production were higher in the group
with FQ or AG resistance (16.7% or 33.3%) than in the group without FQ or AG
resistance (2.9% or 6.4%). Multivariate analyses showed exposures to FQs or AGs
were related to the respective resistances. MBL production was a common factor
for resistance to FQs or AGs, in addition to IPM-resistant P. aeruginosa.
CONCLUSION: As well as promoting appropriate use of antibiotics, MBL production
should be detected as a target of intervention for infection control.
PMID- 28694883
TI - The Diagnosis, Management and Complications Associated with Fractures of the
Talus.
AB - Fractures of the talus are uncommon injuries that can have devastating
consequences. The blood supply to the talus is tenuous and injuries are
associated with a higher incidence of avascular necrosis and malunion. Talar neck
fractures are the most common fractures. This review looks at the different types
of fractures of the talus, particularly focusing on talar neck fractures. The
diagnosis and management are discussed as well as the complications.
PMID- 28694884
TI - Effectiveness of Exercise and Local Steroid Injections for the Thoracolumbar
Junction Syndrome (The Maigne's Syndrome) Treatment.
AB - PURPOSE: Patients diagnosed as thoracolumbar junction syndrome were divided into
3 treatment groups and the results of each modality were compared. MATERIALS AND
METHOD: 30 Patients were included in the study with the definitive diagnosis of
Maigne's Syndrome. The first group received exercise therapy, the second group
was treated with local steroid injections and the third group was the combination
therapy group of both injection and exercise. FINDINGS: 30 Patients were divided
into 3 groups. Each group had 10 patients. The average age of the groups was
detected to be 23.43 +/- 3.75. A flattening was detected in 4 patients of the
first group (40%), 6 patients of the second group (60%) and 4 patients of the
third group (40%) during the lumbar lordosis. While the average difference of the
VAS values was (2.80) as the lowest for the injection group before and after
treatment at rest, the highest value (3.30) was observed in the combined
treatment group. The results shown on the Oswestry scale of the first month
difference (16.10), and the third month difference (22.40) were statistically
better than the other groups in the combined treatment group. RESULTS: As a
result of this study, while in all three treatment groups in the Oswestry scale,
VAS scores at rest or at movement during the regular controls before and after
the treatment showed statistically significant difference; the best results were
obtained in the group administered to the combined injection and exercise
therapy.
PMID- 28694885
TI - Current Concepts and Controversies in Orthopaedic Oncology.
PMID- 28694886
TI - Pediatric Chondrosarcoma of the Sternum Resected with Thorascopic Assistance.
AB - BACKGROUND: Chondrosarcomas are a heterogeneous group of malignant neoplasms that
arise from bones, cartilage or other soft tissues that produce cartilage and are
commonly seen in the middle decades of life. Despite being the most common
primary bone sarcoma in adults, chondrosacromas are rare in pediatric patients.
CASE REPORT: We report the case of a six-year-old child with a painless enlarging
sternal mass of which biopsy was consistent with low-grade surface
chondrosarcoma. This is the first reported case of a chest wall chondrosarcoma in
a young child. This unusual location in a young patient presented challenges to
treatment. Resection of the manubrium was performed by a multidisciplinary team
of orthopaedic oncology and pediatric general surgery. The patient underwent a
wide resection of the sternal mass from an anterior approach performed by the
orthopaedic oncology team using an oscillating saw under video-assisted
thoracoscopic surgery to ensure adequate mass resection without injury to nearby
structures. The patient was followed with quarterly physical exams and
radiographs for 18 months postoperatively and did not have any pain or evidence
of recurrence. CONCLUSION: Clinicians should consider utilizing multidisciplinary
approaches to treat patients with chondrosarcomas of the chest wall.
PMID- 28694887
TI - Injection of Unicameral Bone Cysts with Bone Marrow Aspirate and Demineralized
Bone Matrix Avoids Open Curettage and Bone Grafting in a Retrospective Cohort.
AB - BACKGROUND: Many treatment options exist for unicameral bone cysts (UBC), without
clear evidence of superiority. Meta-analyses have been limited by small numbers
of patients in specific anatomic and treatment subgroups. The purpose of this
study was to report the outcomes of injecting bone marrow aspirate and
demineralized bone matrix (BMA/DBM) for the treatment of proximal humerus UBC.
METHODS: Fifty-one patients with proximal humerus lesions treated by BMA/DBM
injection were retrospectively reviewed from a single academic medical center.
RESULTS: The mean number of injections performed per patient was 2.14 (range 1
5). Eleven patients underwent only one injection (22%), an additional 19 patients
completed treatment after two injections (37%), four patients healed after three
injections (8%), and one patient healed after four injections (2%). The
cumulative success rate of serial BMA/DBM injections was 22% (11/51), 58%
(30/51), 67% (34/51), and 69% (35/51). Eleven patients (22%) ultimately underwent
open curettage and bone grafting, and five patients (10%) were treated with
injection of calcium phosphate bone substitute. CONCLUSION: A BMA/DBM injection
strategy avoided an open procedure in 78% of patients with a proximal humerus
UBC. The majority of patients underwent at least 2 injection treatments. LEVEL OF
EVIDENCE: Level IV retrospective cohort study.
PMID- 28694888
TI - Accuracy and Precision of a Surgical Navigation System: Effect of Camera and
Patient Tracker Position and Number of Active Markers.
AB - INTRODUCTION: Surgical navigation systems are increasingly used to aid resection
and reconstruction of osseous malignancies. In the process of implementing image
based surgical navigation systems, there are numerous opportunities for error
that may impact surgical outcome. This study aimed to examine modifiable sources
of error in an idealized scenario, when using a bidirectional infrared surgical
navigation system. MATERIALS AND METHODS: Accuracy and precision were assessed
using a computerized-numerical-controlled (CNC) machined grid with known
distances between indentations while varying: 1) the distance from the grid to
the navigation camera (range 150 to 247cm), 2) the distance from the grid to the
patient tracker device (range 20 to 40cm), and 3) whether the minimum or maximum
number of bidirectional infrared markers were actively functioning. For each
scenario, distances between grid points were measured at 10-mm increments between
10 and 120mm, with twelve measurements made at each distance. The accuracy
outcome was the root mean square (RMS) error between the navigation system
distance and the actual grid distance. To assess precision, four indentations
were recorded six times for each scenario while also varying the angle of the
navigation system pointer. The outcome for precision testing was the standard
deviation of the distance between each measured point to the mean three
dimensional coordinate of the six points for each cluster. RESULTS: Univariate
and multiple linear regression revealed that as the distance from the navigation
camera to the grid increased, the RMS error increased (p<0.001). The RMS error
also increased when not all infrared markers were actively tracking (p=0.03), and
as the measured distance increased (p<0.001). In a multivariate model, these
factors accounted for 58% of the overall variance in the RMS error. Standard
deviations in repeated measures also increased when not all infrared markers were
active (p<0.001), and as the distance between navigation camera and physical
space increased (p=0.005). Location of the patient tracker did not affect
accuracy (0.36) or precision (p=0.97). CONCLUSION: In our model laboratory test
environment, the infrared bidirectional navigation system was more accurate and
precise when the distance from the navigation camera to the physical (working)
space was minimized and all bidirectional markers were active. These findings may
require alterations in operating room setup and software changes to improve the
performance of this system.
PMID- 28694889
TI - Negative Pressure Wound Therapy for Closed Surgical Wounds in Musculoskeletal
Oncology Patients - A Case-Control Trial.
AB - : Following excision of musculoskeletal tumours, patients are at high risk of
wound issues such as infection, dehiscence and delayed healing. This is due to a
multitude of factors including the invasive nature of the disease, extensive soft
tissue dissection, disruption to blood and lymphatic drainage, residual cavity
and adjuvant therapies. The use of negative pressure wound therapy (NPWT) has a
growing body of evidence on its beneficial effect of wound healing such as
promoting cell differentiation, minimising oedema and thermoregulation.
Traditionally, these dressings have been used for open or dehisced wounds;
however recent research has investigated its role in closed wounds. AIM: To
evaluate the effect of NPWT in patients with closed wounds, either primarily or
with flap coverage, in our high risk group. Consecutive patients who had a NPWT
dressing applied were selected, and a control group was established by a blinded
researcher with matching for tissue diagnosis, surgical site, gender and age. The
primary outcome measured was documented for wound complications, with secondary
data collected on radiotherapy and wound drainage. RESULTS: Patients were well
matched between the intervention (n=9) and control (n=9) groups for gender, age
and tissue diagnosis. Both groups had 1 patient who underwent preoperative
radiotherapy. A total of 3 wound infections occurred in the control group and
none in the NPWT group. Overall there was a trend towards lower drain output and
statistically significantly reduced infection rate in the NPWT group. CONCLUSION:
In this short series, despite the NPWT patients having more additional risk
factors for wound issues, they resulted in fewer infections. The sample size is
not sufficient to have statistically significant reduction. Further evaluation on
the value of NPWT in this patient group should be prospectively evaluated.
PMID- 28694890
TI - A Novel Antibiotic Spacer for Significant Proximal Femoral Loss - Surgical
Technique.
AB - BACKGROUND: Infections of proximal femora with prosthetic implants in situ have
long been a major concern in orthopedic surgery. The gold standard in the
management of infected proximal femurs in the presence of prosthetic implants has
traditionally been a two-stage revision. However, this is challenging in the
setting of extensive bone loss. METHODS: A 3 case series of such infections
leading to extensive loss of the proximal femur is presented. We specifically
describe our technique of debriding the infected segments as well as utilization
of a trochanteric slide osteotomy to resect the femur.We also demonstrate
preparation of the "pseudoacetabulum" and femoral component with an antibiotic
spacer. CONCLUSION: The high cost of such a procedure is offset by reduction in
time spent in hospital. The spacer also helps to allow mobilization by partial
weight bearing on a stable femoral component and provide pain control which
improves quality of life as compared to prolonged intravenous antimicrobial
therapy.
PMID- 28694891
TI - Malignant Transformation of Synovial Chondromatosis: A Systematic Review.
AB - BACKGROUND: Synovial chondromatosis (SCh) can undergo malignant transformation.
Pathologic diagnosis of secondary synovial chondrosarcoma (SChS) is challenging
and misdiagnosis may result in over- or undertreatment. METHOD: A systematic
review revealed 48 cases of SChS published in 27 reports since 1957. Data was
collected to identify findings indicative of SChS and outcomes of treatment.
RESULTS: At median follow-up of 18 months, patients were reported as alive (10%),
alive without disease (22%), alive with disease (15%), dead of disease (19%),
dead of pulmonary embolism (4%), and unknown (29%). Initial diagnosis of SChS
(grade: low/unknown 48%, intermediate/high 52%) was after biopsy in 58%, local
resection in 29%, and amputation in 13%. Seventy-four percent of patients
underwent 1.8 (mean) resections. Patients treated prior to 1992 were managed with
amputation in 79% of cases compared to 48% after 1992. Symptoms were present for
72 mos prior to diagnosis of SChS. Synovial chondrosarcoma demonstrated symptom
progression over several months (82%), rapid recurrence after complete resection
(30%), and medullary canal invasion (43%). The SChS tumor dimensions were seldom
quantified. CONCLUSION: Malignant degeneration of synovial chondromatosis is rare
but can necessitate morbid surgery or result in death. Pathognomonic signs for
SChS including intramedullary infiltration are present in the minority of cases.
Progression of symptoms, quick local recurrence, and muscle infiltration are more
suggestive of SChS. Periarticular cortical erosion, extra-capsular extension, and
metaplastic chondroid features are non-specific. Although poorly documented for
SChS, tumor size is a strong indicator of malignancy. Biopsy and partial
resection are prone to diagnostic error. Surgical decisions are frequently based
on size and clinical appearance and may be in conflict with pathologic diagnosis.
PMID- 28694892
TI - Results of Arthroscopic Repair of Peripheral Triangular Fibrocartilage Complex
Tear With Exploration of Dorsal Sensory Branch of Ulnar Nerve.
AB - BACKGROUND: Ulnar-sided approach in arthroscopic triangular fibrocartilage
complex (TFCC) repair may jeopardize treatment success by exposing the dorsal
sensory branch of ulnar nerve (DSBUN) in risk of injury. We aim to conduct a
follow-up assessment of arthroscopic outside-in TFCC repair and efficacy of
sensory nerve exploration. METHODS: We conducted a retrospective chart review of
58 patients (59 wrists) who received arthroscopic repair of the peripheral
attachment of the TFCC. Ulnar-sided skin incision and exploration of DSBUN were
performed before arthroscopy setting. Arthroscopic outside-in repair through
pullout suture ligation was performed. Functional survey at 6 months and 1 year
postoperatively was based on Mayo Modified Wrist Score (MMWS), and compared to
the preoperative assessment. A p-value of less than 0.05 was considered
significant as calculated using paired t-test. RESULTS: Postoperative MMWS
averaged 74.32+/-11.50 at 6 months, and 84.41+/-9.52 at one year; both showed
significant difference as compared to preoperative status. Significant
improvement was noted in all 4 individual items except motion retrieval between 6
months and 1 year. Totally, 45 (76%) cases achieved good or excellent results at
one year; however, less patients resumed pre-injury activity level when treatment
delay was more than 6 months than those treated earlier (41% vs. 57%).
Complication included 6 transient paresthesia; 1 anchor migration and 1 distal
radioulnar arthrosis. No more nerve complication was found after modification of
perineural dissection. CONCLUSION: Arthroscopy is effective in obtaining both
correct diagnosis and treatment of peripheral TFCC tear. Modified perineural
dissection can minimize sensory nerve complications.
PMID- 28694893
TI - Are We Using Slow-Acting Symptomatic Chondroprotective Drugs Conscious Enough?
AB - BACKGROUND: Osteochondral injuries constitute an entity that is widespread and
can be seen in patients of all ages. Actual treatment modalities aim to relieve
pain, obtain full range of movement of the joint, and improve the quality of
life. There are many slow-acting chondroprotective agents prevalently used in the
United States that are classified as nutritional support but not as medicines .
This study presents the importance of clinical adverse effect profiles as well as
the pharmacological mechanism of action and application of combinations of drugs
that are widely prescribed and not subjected to control. METHODS: Electronic
databases were searched with keywords about the chondroprotective drugs without
any language restriction. Evaluations of the descriptive statistics were
represented via Microsoft Office Excel 2010 lists in the form of a mean+/
standard deviation or frequency (%). The first evaluation showed that 1502
studies were potentially relevant. Following exclusion of the 1277 studies which
were not clinical, full versions of the remaining 225 studies were subjected to
further evaluation. No controlled, blinded, randomized and/or comparative studies
met the inclusion criteria of the study, and no studies evaluated the comparative
clinical results of the hyaluronan of different molecular weights. RESULTS: The
findings of this study concluded that especially when prescribing drugs with
ingredients like GS and CS, many patients' pre-existing conditions must be
considered, such as whether the patient has a glucose intolerance or not.
Additionally, mineral toxication should be considered since the drugs contain
minerals, and after the application of injected hyaluronan, complications should
be considered. CONCLUSION: Clinical, controlled and comparative studies about the
use of chondroprotective drugs must be performed to define the benefits of these
drugs, if any, in order to determine the most suitable time for operative
intervention.
PMID- 28694894
TI - Moxifloxacin Concentration and Proteomic Analysis of Aqueous Humor in Human
Uveitis Associated with Oral Moxifloxacin Therapy.
AB - PURPOSE: The aim was to report the aqueous humor moxifloxacin concentration and
proteome profile of an individual with bilateral uveitis-like syndrome with
pigment dispersion. METHODS: Multiple reactions monitoring mass spectrometry
quantified the aqueous concentration of moxifloxacin in the affected individual.
Shotgun proteomic analysis performed via liquid chromatography tandem mass
spectrometry (LC-MS/MS) defined the protein profile in the affected individual
and unaffected control samples. RESULTS: Moxifloxacin was present at higher than
expected levels in aqueous humor 18 days following oral administration. One-third
of the proteins were identified by significantly lower spectral counts in the
aqueous of the individual with moxifloxacin associated uveitis compared to the
unaffected control. CONCLUSION: Moxifloxacin was detected in aqueous humor 18
days following the completion of oral administration. These results suggest that
moxifloxacin toxicity may be responsible for the uveitis-like syndrome with
pigment dispersion syndrome induced by moxifloxacin therapy.
PMID- 28694895
TI - Surgery of the elderly in emergency room mode. Is there a place for laparoscopy?
AB - INTRODUCTION: An important yet difficult problem is qualification for surgery in
elderly patients. With age the risk of comorbidities increases - multi-disease
syndrome. Elderly patients suffer from frailty syndrome. Many body functions
become impaired. All these factors make the elderly patient a major challenge for
surgical treatment. AIM: Analysis of the possibility of developing the
indications and contraindications and the criteria for surgical treatment of the
elderly based on our own cases. Discussion whether there is a place for
laparoscopy during surgery of the elderly in emergency room (ER) mode. MATERIAL
AND METHODS: The analysis was performed based on seven cases involving surgical
treatment of elderly patients who were admitted to the hospital in emergency room
mode. The patients were hospitalized in the General and Minimally Invasive
Surgery Clinic in Olsztyn in 2016. RESULTS: Surgical treatment of elderly
patients should be planned with multidisciplinary teams. Geriatric surgery
centers should be developed to minimize the risk of overzealous treatment and
potential complications. Laparoscopy should always be considered in the case of
ER procedures or diagnostics. CONCLUSIONS: Elderly patients should not be treated
as typical adults, but as a separate group of patients requiring special
treatment. Due to the existing additional disease in the elderly, the frailty
syndrome, any surgical intervention should be minimally invasive. The discussion
about therapy should be conducted by a team of specialists from a variety of
medical fields.
PMID- 28694896
TI - Laparoscopically assisted colonoscopic polypectomy - viable option for curative
surgery in elderly patients.
AB - INTRODUCTION: Colorectal cancer (CRC) is the third most common cancer worldwide
and the fourth most frequent cause of cancer-related death in the world. CRC
screening programs have been widely introduced worldwide, allowing for early
detection and removal of precancerous lesions and avoiding major surgical
intervention. However, not all polyps are suitable for conventional and advanced
colonoscopic polypectomy. Thus, laparoscopically assisted colonoscopic
polypectomy (LACP) was introduced to clinical practice as a method of choice for
these polyps and adenomas. AIM: To overlook our experience in laparoscopically
assisted colonoscopic polypectomies and evaluate effectiveness and quality of the
procedure. MATERIAL AND METHODS: A retrospective analysis of a prospectively
maintained database was performed. using the Vilnius University Hospital
Santariskiu Klinikos patient database for the period from 2010 to 2016, resulting
in 21 cases in which LACP was performed. All procedures were performed using
combined laparoscopy and videocolonoscopy techniques. Morphology of adenomas was
classified according to the Paris classification during the procedure. Creation
of the database was approved by the Lithuanian Bioethics committee. RESULTS:
Twenty-two adenomas were removed from 21 patients, aged 65.33 +/-8.9. There was
no difference between male and female age, but occurrence of adenomas in females
was 2-fold higher. The majority of removed lesions were localized in the cecum
and mean size was 27.2 +/-11.1 mm. The morphology of adenomas was distributed
equally between 0-Is, 0-Ip, and 0-IIa, except one, which belonged to 0-III.
Histological analysis revealed that tubulovillous adenoma occurrence was 1.4
times higher than tubulous adenoma. There was only one postoperative complication
- bleeding from the adenoma resection site, which was managed by conservative
means. One patient developed G2 adenocarcinoma at the polyp resection site and
was referred for radical surgery. CONCLUSIONS: The LACP is a safe procedure with
minimal risk to the elderly patient. Patient follow-up is essential for detection
of recurrence.
PMID- 28694897
TI - The effects of prolonged CO2 insufflation on kidney function in a rat
pneumoperitoneum model.
AB - INTRODUCTION: Pneumoperitoneum (PP) is known to cause ischemia in kidneys and
other intra-abdominal organs because of decreased splanchnic blood flow. AIM: We
aimed to determine the degree of renal injury that occurs due to a PP and
prolonged PP. We measured renal injury biomarkers and made a histopathological
evaluation to estimate the degree of injury and assessed the correlation of
biomarkers with histopathological findings. MATERIAL AND METHODS: Twenty-one
female Sprague Dawley rats were separated randomly into three groups. Group 1 was
the control group and was given anesthesia for 3 h. In group 2, a PP was
administered under anesthesia for 1 h. A pneumoperitoneum was administered under
anesthesia to animals in group 3 for 3 h. RESULTS: Pathological analysis showed a
significant statistical difference between the 3 groups. In particular,
neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C (Cys C) levels
at the 24th h and preoperative mean urea levels showed a significant difference
between the groups. The 24th-hour NGAL level in group 3 was significantly higher
than that of group 1. The preoperative Cys C level was higher in group 1 than in
either group 2 or 3. Cys C was decreased significantly in group 1 and increased
significantly in both groups 2 and 3. CONCLUSIONS: The increase in NGAL and Cys C
levels directly correlated with the duration of PP and intra-abdominal pressure,
and they are therefore good biomarkers in diagnosing acute renal injury in the
early phase. Serum creatinine level is not a good biomarker in the early phase of
renal injury.
PMID- 28694898
TI - Histopathological examination of tissue resected during bariatric procedures - to
be done or not to be done?
AB - INTRODUCTION: Obesity is one of the major lifestyle diseases and provokes various
comorbidities, such as hypertension, type 2 diabetes mellitus, obstructive sleep
apnea, and even neoplasms. Bariatric surgery is the most effective treatment of
obesity. Since cost-effectiveness has become a major concern, there is a tendency
to avoid general histological evaluation of surgical specimens during routine
procedures. AIM: To evaluate the necessity of histopathological investigation of
tissue excised during bariatric surgery and to verify whether the operation
should be continued in the case of suspicious macroscopic findings. MATERIAL AND
METHODS: From January 2013 to December 2016, 1252 patients with obesity were
qualified for bariatric procedures. The qualification was performed according to
the current European recommendations. Every operation started with an inspection
of the peritoneal cavity performed once the abdomen was insufflated. If a
macroscopic pathology was found, the specimen was secured for histopathological
investigation. RESULTS: Out of 81 (6.47%) patients from whom histopathological
samples were collected, 39% (n = 32) showed negative results, and 61% (n = 49)
cases showed abnormalities. CONCLUSIONS: As it is impossible to exclude the
existence of gastric tumors only in preoperative gastroscopy and ultrasonography,
especially as there is a higher risk in obese patients, routine histological
examination of tissue excised during bariatric procedures should be considered.
Since most of the neoplasms were found to be benign, there is no need to abandon
the bariatric procedure if a pathology is found and resected. Bariatric surgeons
should always focus on thorough examination of the abdominal and the pelvic
cavity, especially in female patients.
PMID- 28694899
TI - Comparison of circular- and linear-stapled gastrojejunostomy in laparoscopic Roux
en-Y gastric bypass: a multicenter study.
AB - INTRODUCTION: Laparoscopic Roux-en-Y gastric bypass (LRYGB) is a common, well
established procedure, but no consensus regarding selection of the
gastrojejunostomy (GJ) technique has been reached, and standardization of this
precise technique is far from being achieved. AIM: To compare circular-stapled
and linear-stapled GJ in LRYGB in terms of operative time and postoperative
complications. MATERIAL AND METHODS: This retrospective case-control study
compared the perioperative and postoperative outcomes of LRYGB with a circular
stapled (LRYGB-CS) versus linear-stapled (LRYGB-LS) gastrojejunostomy. All
patients, operated on in two academic referral care centers for bariatric
surgery, were enrolled from April 2013 to June 2016. 457 patients were included
(255 and 202 respectively in the LRYGB-CS and LRYGB-LS groups). After matching
the groups for age, sex, body mass index, arterial hypertension, and presence of
type 2 diabetes in a 1 : 1 ratio, 99 patients were enrolled in each. RESULTS: The
total operative time was longer in the LRYGB-LS group (140 vs. 85 min, p <
0.001). The postoperative hemorrhage and wound infection rates were lower in the
LRYGB-LS group (2.1% vs. 10.3%, p = 0.021, and 1.0% vs. 9.3%, p = 0.011). The
readmission rates were comparable (8.2% vs. 6.1%, p = 0.593). There was no
significant difference in the incidence of gastrojejunostomy leakage, stricture,
port-site hernia, or marginal ulcer. CONCLUSIONS: Both anastomosis types for
LRYGB are safe and have low and comparable risks of postoperative complications.
After LRYGB-CS, postoperative bleeding and wound infections are slightly more
frequent; however, the operative time is shorter.
PMID- 28694900
TI - A prospective 4-year study of insulin resistance and adipokines in morbidly obese
diabetic and non-diabetic patients after gastric banding.
AB - INTRODUCTION: There are insufficient data regarding the changes in adipokine
levels after laparoscopic adjustable gastric banding (LAGB) in diabetic and non
diabetic patients and their effects on insulin resistance and type 2 diabetes
remission. AIM: To assess leptin, adiponectin, and insulin resistance changes
after LAGB in diabetic and non-diabetic morbidly obese patients. MATERIAL AND
METHODS: One hundred and three patients (37 with and 66 without type 2 diabetes)
underwent LAGB from January 2009 to January 2010. Glycated hemoglobin, insulin,
adipokine levels and insulin resistance were evaluated preoperatively, and 1 and
4 years after LAGB. RESULTS: The mean patient age was 45.9 +/-11.7 years and mean
preoperative body mass index was 47.5 +/-7.3 kg/m2. A total of 80 of 103 patients
(77.6%) completed the 4-year follow-up. After 4 years the mean excess weight loss
was 38.8% and 39.5% in diabetic and non-diabetic patients respectively. Leptin
levels decreased significantly in both groups at 1 year, but after 4 years this
was noted only in non-diabetic patients. After 1 year adiponectin levels
increased significantly only in non-diabetic patients (p = 0.003) and remained
almost the same at 4 years. A significant decrease in insulin resistance was
noted in both groups 1 year after LAGB and diabetes remission was observed in 23
(62.1%) patients. There was a negative correlation between preoperative insulin
resistance and adiponectin levels throughout the follow-up period. Leptin levels
positively correlated with BMI throughout the study period (baseline r = 0.45; p
< 0.001; after 1 year r = 0.71; p < 0.001; after 4 years r = 0.68; p < 0.001).
There was no significant correlation between leptin and adiponectin
concentrations preoperatively or after 1 year; however, at 4 years it was
significant (r = 0.27; p < 0.02). CONCLUSIONS: The most significant metabolic
changes occurred within 1 year after LAGB. The 4-year follow-up revealed
stabilization in metabolic indices rather than significant improvement.
PMID- 28694901
TI - Staple line leak with peritonitis after laparoscopic sleeve gastrectomy - a
solution in one to six steps.
AB - INTRODUCTION: Laparoscopic sleeve gastrectomy (LSG) is one of the most efficient
bariatric interventions in morbidly obese patients. The most severe risk of this
procedure seems to be the staple line leak, and the management of this
complication can be very arduous. AIM: To share our experience in managing the
staple line leak after LSG and to help to find the best procedure that should be
preferred. MATERIAL AND METHODS: In the 2010-2015 period we performed 223 LSG,
with about 5 demonstrating severe complications - two patients with severe
bleeding requiring revision surgery, and three patients with resection surface
leak. RESULTS: We always primarily treated the staple line leak with a
laparoscopic revision. Once the fistula did not spontaneously close after this
treatment. A series of other methods were then indicated for this patient and
only the sixth one resulted in the desirable therapeutic success. At first, our
team opted for laparoscopic revision with drainage. The next procedure involved
applying Ovesco and Boston clips. As a third method we performed abscess drainage
through a nasobiliary tube inserted via gastroscopy. Due to failure we performed
the second laparoscopic revision with staple line resuture, the next intervention
was an open revision with fistula excision and suture, and finally we opted for
the application of a self-expanding metallic stent, which proved to be definitely
curative. CONCLUSIONS: Without any guidelines it is very difficult to determine
the right procedure addressing the staple line leak after LSG. It depends mainly
on the clinician's experience and is lengthy and often untraditional.
PMID- 28694902
TI - Clinical evaluation of C-reactive protein and procalcitonin for the early
detection of postoperative complications after laparoscopic sleeve gastrectomy.
AB - INTRODUCTION: Among the most common early complications after bariatric surgery
are anastomosis leak and bleeding. In order to react quickly and perform accurate
treatment before the clinical signs appear, early predictors should be found. In
the study C-reactive protein (CRP) and procalcitonin (PCT) levels were
investigated. Characterized by a relatively short half-life, they can predict
surgical complications. AIM: To develop and implement certain standards for early
detection of complications. MATERIAL AND METHODS: The study involved 319 adults
who underwent laparoscopic sleeve gastrectomy (LSG) as a surgical intervention
for morbid obesity at the Department of General Surgery of Ceynowa Hospital in
Wejherowo. Every patient had CRP and PCT levels measured before the surgery and
on the 1st and 2nd postoperative day (POD). RESULTS: Early postoperative
complications occurred in 19 (5.96%) patients. Septic and non-septic
complications occurred in 3 and 16 patients respectively. Among the patients with
septic postoperative complications CRP level increased significantly on the 2nd
POD compared to the remainder (p = 0.0221). Among the patients with non-septic
postoperative complications CRP level increased significantly on the 1st and 2nd
POD compared to the remainder. Among the patients with septic and non-septic
postoperative complications PCT level increased significantly on the 2nd POD
compared to the remainder. CONCLUSIONS: The CRP and PCT level are supposed to be
relevant diagnostic markers to predict non-septic and septic complications after
LSG.
PMID- 28694903
TI - Treatment of impalpable testis - one clinic's experience.
AB - INTRODUCTION: Undescended testes are recognised in 1% to 2% of boys during the
first year of life, and about 20% of them are impalpable. Ultrasonography (US)
may establish the localisation of the testis but the final diagnosis is usually
determined laparoscopically. AIM: To evaluate long-term results of laparoscopic
treatment of boys with impalpable testes and sensitivity of preoperative
ultrasound. MATERIAL AND METHODS: Between 2011 and 2015, we operated on 545 boys
with undescended testes. Sixty-two of them with 65 impalpable testes were treated
laparoscopically - the study group. Mean age was 3.5 years. The study group was
divided into 5 groups according to type of treatment. The volume and position of
the operated gonad were assessed manually and by ultrasound. RESULTS: In group 1
testicular agenesis was observed in 19 patients. In group 2 revision of the
inguinal canal revealed testicular agenesis in 7 and atrophy in 4 patients. In
group 3 conversion to classic orchiopexy was performed in 10 patients. In group 4
one-stage orchiopexy was performed in 9 patients on 12 testes. In group 5 a two
stage F-S procedure was performed in 13 patients. Ten testes in group 4 had a
volume in the normal range (84%) and also 10 testes in group 5 (77%).
CONCLUSIONS: Laparoscopy in impalpable testes is the procedure of choice and
allows definitive management, even when conversion to open procedure is
necessary. Sensitivity of preoperative ultrasound is generally about 60% for true
intra-abdominal testes, so diagnostic laparoscopy is necessary.
PMID- 28694904
TI - Transapical aortic valve implantation using a Symetis Acurate self-expandable
bioprosthesis: initial outcomes of 10 patients.
AB - INTRODUCTION: Transapical aortic valve implantation (TA-AVI) has been widely
introduced for treatment of patients with severe aortic stenosis in the last
decade. Here we report our first clinical experience with 10 patients using the
second-generation transapical Symetis Acurate TA aortic valve designed for
transapical implantation. AIM: To evaluate the results of transapical access in
transcatheter aortic valve implantation (TAVI) among patients with unsuitable
vascular access. MATERIAL AND METHODS: All patients had been assessed by a local
heart team and were disqualified from surgical aortic valve replacement (AVR) and
the transfemoral TAVI approach. Mean age was 75.4 +/-3.9 years (range: 68-80),
with 20% being female. Logistic EuroSCORE (European System for Cardiac Operative
Risk Evaluation) and STS (Society of Thoracic Surgeons) were 15.4 +/-8.9% and
20.5 +/-4.5%, respectively. RESULTS: All implantations were performed
successfully in the intra-annular and subcoronary position. There were no
conversions to surgical AVR. All patients survived 30-day follow-up. No strokes
or transient ischemic attacks were reported. There was no need for pacemaker
implantation and none of the patients demonstrated moderate or significant
paravalvular leakage. The mean aortic gradients improved significantly from a
baseline of 57.0 +/-19.2 mm Hg to a 30-day value of 14.2 +/-4.1 mm Hg.
CONCLUSIONS: Our initial clinical results indicate satisfactory functionality in
patients after trans-apical implantation of the Symetis Acurate aortic valve. The
procedure of implantation seems to be straightforward and may be considered in
patients in whom a transfemoral approach is not a good option.
PMID- 28694905
TI - Mid-term follow-up outcomes of 2-staged hybrid coronary revascularization
compared with off-pump coronary artery bypass for patients with multivessel
coronary artery disease.
AB - INTRODUCTION: Two-staged hybrid coronary revascularization (HCR) is a novel
procedure in selected patients with multivessel coronary artery disease. However,
few studies are available on the mid-term or long-term outcomes of this 2-staged
procedure as compared to off-pump coronary artery bypass (OPCAB). AIM: To compare
in-hospital and mid-term follow-up outcomes of 2-staged HCR with OPCAB in
patients with multivessel coronary artery disease. MATERIAL AND METHODS: The
present retrospective study analyzed the data from 73 patients who underwent the
2-staged HCR (HCR group) during 2012-2014 at the heart center. Three hundred and
eighty-three patients who underwent conventional OPCAB by the same surgeon were
selected for the comparative analysis performed on in-hospital and mid-term
follow-up outcomes between the two groups. RESULTS: No significant difference was
observed in the preoperative outcome between the two groups. The HCR group had a
shorter operation duration (152.9 +/-43.8 vs. 262.6 +/-51.8 min, p < 0.05), less
bleeding (558.6 +/-441.3 vs. 1035.5 +/-613.3 ml, p < 0.05), shorter mechanical
ventilation (9.4 +/-7.4 vs. 19.0 +/-18.3 h, p < 0.05), and less blood transfusion
(12 (16.4%) vs. 200 (52.2%), p < 0.05). The mean follow-up duration was 25.0 +/
9.6 months in the HCR group and 22.8 +/-10.6 months in the OPCAB group. The
incidence of major adverse cardiac or cerebrovascular events (MACCE) was similar
in both groups (4 (5.5%) vs. 10 (2.8%), p = 0.408). The estimated 3-year survival
was similar in both groups (log-rank chi2 = 1.041, p = 0.308). CONCLUSIONS: The 2
staged HCR is a safe and effective surgical procedure and may offer similar mid
term follow-up outcomes to OPCAB.
PMID- 28694906
TI - Abdominal tuberculosis after removal of an adjustable gastric band - report of an
unusual case.
AB - Laparoscopic adjustable gastric banding (LAGB) is the third most popular
bariatric procedure. Despite its reversibility and minimal invasiveness, band
infection affects 1.2% of patients. We present a case of a 25-year-old, obese
woman who was experiencing malaise and feverishness 3 years after gastric band
placement. Due to port site infection the port was removed, which did not improve
the patient's condition. After 2 years the band was removed via laparotomy with a
minor surgical site infection reported. The patient returned 2 weeks after
discharge with signs of sepsis. After ruling out pulmonary causes, an exploratory
laparotomy was performed, revealing granulomatous peritonitis. Standard
histopathological examinations, broncho-alveolar lavage culture and DNA tests
along with microbiological cultures were inconclusive. Broad-spectrum antibiotics
and antifungal and antiparasitic agents did not improve the patient's condition.
Mycobacterium tuberculosis DNA was discovered in a greater omentum specimen. The
patient was treated with isoniazid, rifampicin, pyrazinamide and streptomycin for
four months.
PMID- 28694907
TI - Laparoscopic diaphragmatic hernia repair using expanded polytetrafluoroethylene
(ePTFE) for delayed traumatic diaphragmatic hernia.
AB - Traumatic diaphragmatic hernia (TDH) is an uncommon surgical problem, and
diagnosis is often delayed. However, the mortality from bowel necrosis can reach
80%. Therefore, suspicion is needed and surgery is required to prevent
complications. A 50-year-old man was transferred due to abdominal pain and
vomiting. Chest X-ray and computed tomography (CT) scan showed herniation of the
stomach through the left diaphragm. The patient had fallen down 15 months ago and
CT scan at that time revealed a small defect of the diaphragm without herniation.
We diagnosed delayed herniation of TDH and the patient underwent laparoscopic
repair using an expanded polytetrafluoroethylene (ePTFE) mesh. Recovery was
uneventful and the CT scan at 3 months after the operation showed no recurrence.
We reported a delayed presenting TDH and considered a laparoscopic approach to be
safe and feasible during elective surgery. Moreover, use of an ePTFE mesh for
repair of large diaphragmatic hernia was also feasible.
PMID- 28694908
TI - An unusual case of aortic rupture after deployment of a bare stent in the
treatment of aortic dissection in a patient with giant-cell arteritis.
AB - Giant-cell arteritis is associated with a higher risk of aortic aneurysm and
aortic dissection formation. We present a women with aortic dissection type B
treated with a stent graft and bare-metal stent implantation. After the stent
deployment we noticed aortic rupture, which was successfully treated with
implantation of an additional stent graft. This report highlights the difficulty
of endovascular therapy in patients with giant-cell arteritis. We have to bear in
mind that chronic inflammation of the aorta leads to a more fragile aortic wall
than normal. We recommend the use of a stent graft over a bare-metal stent and
gentle use of a balloon catheter.
PMID- 28694910
TI - Retraction note.
AB - [This retracts the article DOI: 10.5114/wiitm.2017.66025.].
PMID- 28694909
TI - Endoscopic treatment of multilocular walled-off pancreatic necrosis with the
multiple transluminal gateway technique.
AB - The development of minimally invasive techniques allowed access to the necrotic
cavity through transperitoneal, retroperitoneal, transmural and transpapillary
routes. The choice of access to walled-off pancreatic necrosis (WOPN) should
depend not only on the spread of necrosis, but also on the experience of the
clinical center. Herein we describe treatment of a patient with multilocular
symptomatic walled-off pancreatic necrosis using minimally invasive techniques.
The single transmural access (single transluminal gateway technique - SGT) to the
necrotic collection of the patient was ineffective. The second gastrocystostomy
was performed using the same minimally invasive technique as an extra way of
access to the necrosis (multiple transluminal gateway technique - MTGT). In the
described case the performance of the new technique consisting in endoscopic
multiplexing transmural access (MTGT) was effective enough and led to complete
recovery of the patient.
PMID- 28694911
TI - Pilomatrixoma Presenting as a Rapidly Expanding Mass of the Infant Nasion.
AB - Objective: Pilomatrixomas are benign neoplasms originating from the cells of hair
follicles. They typically present as a slowly enlarging, solitary mass on hair
bearing areas of the head and neck. While a common childhood lesion,
pilomatrixomas are unusual in infancy. Our objective is to present an atypical
pilomatrixoma located on the midline nasion of an 11-month-old as such a lesion
and its management has not been previously described. Methods: Despite
preoperative diagnostic imaging, including computed tomography and magnetic
resonance imaging, the diagnosis was not made until examination by pathology
after complete surgical excision. We also completed a thorough review of the
literature pertaining to pilomatrixomas, which is presented in a concise fashion.
Results: Our patient's clinical presentation did not correlate with traditional
descriptions in the literature, skewing preoperative diagnosis. However, surgical
management was ultimately appropriate and effective. To date, the patient has not
demonstrated evidence of recurrence. Conclusion: We believe that this is the
first such reported presentation of a pilomatrixoma. Given its incidence, we
encourage readers to consider this diagnosis when evaluating similar pediatric
skin lesions of the head and neck. Complete surgical excision is the definitive
treatment.
PMID- 28694912
TI - Posterior Auricular Mass.
PMID- 28694913
TI - The Role of Free Radicals in Hemolytic Toxicity Induced by Atmospheric-Pressure
Plasma Jet.
AB - Atmospheric-pressure plasma (APP) has received attention due to its generation of
various kinds of reactive oxygen/nitrogen species (ROS/RNS). The controllability,
as well as the complexity, is one of the strong points of APP in various
applications. For biological applications of this novel method, the cytotoxicity
should be estimated at various levels. Herein, we suggest red blood cell (RBC) as
a good cell model that is simpler than nucleated cells but much more complex than
other lipid model systems. Air and N2 gases were compared to verify the main
ROS/RNS in cytotoxicity, and microscopic and spectroscopic analyses were
performed to estimate the damages induced on RBCs. The results shown here will
provide basic information on APP-induced cytotoxicity at cellular and molecular
levels.
PMID- 28694914
TI - Omega-3 Polyunsaturated Fatty Acids in Critical Illness: Anti-Inflammatory,
Proresolving, or Both?
AB - Prognosis and outcomes of critically ill patients are strictly related with
inflammatory status. Inflammation involves a multitude of interactions between
different cell types and chemical mediators. Omega-3 polyunsaturated fatty acids
(PUFAs), mainly represented by eicosapentaenoic acid (EPA) and docosahexaenoic
acid (DHA), are able to inhibit different pathways including leukocyte
chemotaxis, adhesion molecule expression and interactions, and production of
inflammatory cytokines, through the action of specialized proresolving mediators
(SPMs). SPMs from omega-6 fatty acids, such as lipoxins, and from omega-3 fatty
acids such as resolvins, protectins, and maresins, act in reducing/resolving the
inflammatory process in critical diseases, stimulating the phases of resolution
of inflammation. In this light, the resolution of inflammation is nowadays
considered as an active process, instead of a passive process. In critical
illness, SPMs regulate the excessive posttrauma inflammatory response, protecting
organs from damage. This review focuses on the role of omega-3 PUFAs as pharma
nutrition agents in acute inflammatory conditions, highlighting their effects as
anti-inflammatory or proresolving agents.
PMID- 28694915
TI - Heme Oxygenase-1, a Key Enzyme for the Cytoprotective Actions of Halophenols by
Upregulating Nrf2 Expression via Activating Erk1/2 and PI3K/Akt in EA.hy926
Cells.
AB - Increasing evidence has demonstrated that heme oxygenase-1 (HO-1) is a key enzyme
triggered by cellular stress, exhibiting cytoprotective, antioxidant, and anti
inflammatory abilities. Previously, we prepared a series of novel active
halophenols possessing strong antioxidant activities in vitro and in vivo. In the
present study, we demonstrated that these halophenols exhibited significant
protective effects against H2O2-induced injury in EA.hy926 cells by inhibition of
apoptosis and ROS and TNF-alpha production, as well as induction of the
upregulation of HO-1, the magnitude of which correlated with their cytoprotective
actions. Further experiments which aimed to determine the mechanistic basis of
these actions indicated that the halophenols induced the activation of Nrf2,
Erk1/2, and PI3K/Akt without obvious effects on the phosphorylation of p38, JNK,
or the expression of PKC-delta. This was validated with the use of PD98059 and
Wortmannin, specific inhibitors of Erk1/2 and PI3K, respectively. Overall, our
study is the first to demonstrate that the cytoprotective actions of halophenols
involve their antiapoptotic, antioxidant, and anti-inflammatory abilities, which
are mediated by the upregulation of Nrf2-dependent HO-1 expression and reductions
in ROS and TNF-alpha generation via the activation of Erk1/2 and PI3K/Akt in
EA.hy926 cells. HO-1 may thus be an important potential target for further
research into the cytoprotective actions of halophenols.
PMID- 28694916
TI - The Protective Effect of Indole-3-Acetic Acid (IAA) on H2O2-Damaged Human Dental
Pulp Stem Cells Is Mediated by the AKT Pathway and Involves Increased Expression
of the Transcription Factor Nuclear Factor-Erythroid 2-Related Factor 2 (Nrf2)
and Its Downstream Target Heme Oxygenase 1 (HO-1).
AB - Indole-3-acetic acid (IAA) is the most common plant hormone of the auxin class
and is known to have many effects including cell proliferation enhancement and
antioxidant property. However, no study has revealed its defensive effects
against oxidative toxicity in human dental pulp stem cells (hDPSCs). In this
study, we investigated the effects of IAA on hydrogen peroxide- (H2O2-) induced
oxidative toxicity in hDPSCs. H2O2-induced cytotoxicity was attenuated after IAA
treatment. Cell cycle analysis using FACS showed that the damaged cell cycle and
increased number of apoptotic cells by H2O2 treatment were recovered after the
treatment of IAA. The H2O2-mediated increased expression of the proapoptotic
genes, BAX and p53, was attenuated by IAA treatment, while IAA treatment
increased antiapoptotic genes, BCL-2 and ATF5 expression. The increases of
cleaved caspase-3 and ROS by H2O2 were also decreased after treatment of IAA. To
further investigate the mechanism of IAA, Nrf2-related antioxidant pathway was
examined and the results showed that the level of Nrf2 and HO-1 expressions,
stimulated by H2O2, decreased after treatment of IAA. Moreover, IAA treatment
protected hDPSCs against H2O2-induced oxidative stress via increased expression
of Nrf2 and HO-1, mediated by the AKT pathway.
PMID- 28694917
TI - Complete genome sequence of Microbulbifer sp. CCB-MM1, a halophile isolated from
Matang Mangrove Forest, Malaysia.
AB - Microbulbifer sp. CCB-MM1 is a halophile isolated from estuarine sediment of
Matang Mangrove Forest, Malaysia. Based on 16S rRNA gene sequence analysis,
strain CCB-MM1 is a potentially new species of genus Microbulbifer. Here we
describe its features and present its complete genome sequence with annotation.
The genome sequence is 3.86 Mb in size with GC content of 58.85%, harbouring 3313
protein coding genes and 92 RNA genes. A total of 71 genes associated with
carbohydrate active enzymes were found using dbCAN. Ectoine biosynthetic genes,
ectABC operon and ask_ect were detected using antiSMASH 3.0. Cell shape
determination genes, mreBCD operon, rodA and rodZ were annotated, congruent with
the rod-coccus cell cycle of the strain CCB-MM1. In addition, putative mreBCD
operon regulatory gene, bolA was detected, which might be associated with the
regulation of rod-coccus cell cycle observed from the strain.
PMID- 28694918
TI - Alteration of circadian rhythm during epileptogenesis: implications for the
suprachiasmatic nucleus circuits.
AB - It is important to realize that characterization of the circadian rhythm patterns
of seizure occurrence can implicate in diagnosis and treatment of selected types
of epilepsy. Evidence suggests a role for the suprachiasmatic nucleus (SCN)
circuits in overall circadian rhythm and seizure susceptibility both in animals
and humans. Thus, we conclude that SCN circuits may exert modifying effects on
circadian rhythmicity and neuronal excitability during epileptogenesis. SCN
circuits will be studied in our brain centre and collaborating centres to explore
further the interaction between the circadian rhythm and epileptic seizures. More
and thorough research is warranted to provide insight into epileptic seizures
with circadian disruption comorbidities such as disorders of cardiovascular
parameters and core body temperature circadian rhythms.
PMID- 28694919
TI - 8-pCPT-cGMP prevents mitochondrial depolarization and improves the outcome of
steatotic partial liver transplantation.
AB - Permeant cGMP analogs prevent the mitochondria permeability transition (MPT) in
vitro. In this study, we explored whether 8-pCPT-cGMP prevents the MPT and
decreases post-transplant damage to fatty partial liver grafts (FPG) in vivo.
Rats were fed a control or high-fat, high-fructose diet for 2-week. Lean and
fatty liver explants were reduced in size ex vivo to ~35% and stored in the
University of Wisconsin solution with and without 8-pCPT-cGMP (300 uM) for 2 h.
After transplantation, alanine aminotransferase release (indicator of
hepatocellular injury), hyperbilirubinemia (indicator of poor liver function),
and cell death were all higher in FPG than in lean partial grafts (LPG). Liver
regeneration increased in LPG but was suppressed in FPG. 8-pCPT-cGMP blunted
graft injury, improved liver regeneration and function, and increased survival of
FPG. Hepatic mitochondrial depolarization detected by intravital multiphoton
microscopy of rhodamine 123 in living rats was ~3.5-fold higher in FPG than in
LPG. 8-pCPT-cGMP decreased mitochondrial depolarization in FPG almost to the
level of LPG. Activation of mammalian target of rapamycin (mTOR), an energy
sensitive kinase that stimulates cell proliferation and growth, and p70S6 kinase,
a downstream signaling molecule of mTOR, was increased in LPG but suppressed in
FPG. 8-pCPT-cGMP restored the activity of mTOR and p70S6 kinase in FPG. 8-pCPT
cGMP also increased activation of cAMP response element-binding protein (CREB)
and expression of cyclins D1 and E in FPG. Non-alcoholic steatosis increases
injury and suppresses regeneration after partial liver transplantation, at least
in part, due to more severe mitochondrial dysfunction. Protection of mitochondria
with a cGMP analog effectively improves outcomes of FPG transplantation.
PMID- 28694921
TI - Generating CNS organoids from human induced pluripotent stem cells for modeling
neurological disorders.
AB - Understanding human brain development and disease is largely hampered by the
relative inaccessibility of human brain tissues. Recent advances in human induced
pluripotent stem cells (hiPSCs) have led to the generation of unlimited human
neural cells and thereby facilitate the investigation of human brain development
and pathology. Compared with traditional 2-dimensional (2D) culture methods,
culturing the hiPSC-derived neural cells in a three-dimensional (3D) free
floating manner generates human central nervous system (CNS) organoids. These 3D
CNS organoids possess the unique advantage of recapitulating multi-regional or
region-specific cytoarchitecture seen in the early human fetal brain development.
The CNS organoids are becoming a strong complement to the animal model in
studying brain development and pathology, and developing new therapies to treat
neurodevelopmental diseases. Further improvements to the long-term maintenance
and neural maturation of the organoids may allow them to model neurodegenerative
diseases. In this review, we will summarize the current development of hiPSCs to
generate CNS organoids for modeling neurological disorders and future
perspective.
PMID- 28694920
TI - Role of microglia in methamphetamine-induced neurotoxicity.
AB - Methamphetamine (Meth) is an addictive psychostimulant widely abused around the
world. The chronic use of Meth produces neurotoxicity featured by dopaminergic
terminal damage and microgliosis, resulting in serious neurological and
behavioral consequences. Ample evidence indicate that Meth causes microglial
activation and resultant secretion of pro-inflammatory molecules leading to
neural injury. However, the mechanisms underlying Meth-induced microglial
activation remain to be determined. In this review, we attempt to address the
effects of Meth on human immunodeficiency virus (HIV)-associated microglia
activation both in vitro and in-vivo. Meth abuse not only increases HIV
transmission but also exacerbates progression of HIV-associated neurocognitive
disorders (HAND) through activation of microglia. In addition, the therapeutic
potential of anti-inflammatory drugs on ameliorating Meth-induced microglia
activation and resultant neuronal injury is discussed.
PMID- 28694922
TI - Untypable genotype restriction patterns and surface gene variants of hepatitis B
virus isolates.
AB - Chronic hepatitis B is a global health problem, and is one of the leading causes
of cirrhosis and hepatocellular carcinoma. Hepatitis B virus (HBV) genotyping
helps in decision making for clinical management of HBV infection, and is
important for epidemiological studies. The objectives of this study were to
investigate the distribution of HBV genotypes circulating in the Philippines;
molecularly characterize untypable genotype restriction patterns; and analyze the
presence of surface gene variants. HBV genotypes were determined by restriction
fragment length polymorphism (RFLP) and DNA sequencing. Three genotypes, HBV A
(76%; 73/96), HBV B (10%; 10/96) and HBV C (14%; 13/96) were detected by RFLP.
Out of the 96 isolates, 9% were untypable by RFLP analysis. DNA sequencing
followed by phylogenetic analysis revealed that these isolates belonged to HBV
genotypes A (67%; 6/9), B (11%; 1/9) and C (22%; 2/9). Out of the 9 isolates, 55%
showed single or multiple variations which resulted to amino acid changes.
Overall, the identification of untypable genotype can be resolved by sequence and
phylogenetic analysis of the S gene and this approach can also be used to detect
single or multiple variants. Our findings underscore the importance of accurate
genotyping and detection of surface gene variants by DNA sequencing for optimal
clinical management.
PMID- 28694923
TI - Molecular genetic changes in benign colorectal tumors synchronous with
microsatellite unstable carcinomas do not support a field defect.
AB - BACKGROUND: A colorectal cancer may develop through a particular molecular
genetic pathway, raising the question of whether the particular molecular changes
are random, or are unique to the particular segment of colon. We wanted to
determine whether molecular changes found within a colorectal cancer might also
be detected in separate adenomas and polyps removed from the same area of colon
at surgery. Microsatellite instability was chosen as a marker for a pathway of
colon carcinogenesis. METHODS: We studied a total of 46 primary colorectal
cancers with microsatellite instability and 77 synchronous adenomas and polyps.
All tumors were evaluated for microsatellite instability, BRAF and KRAS
mutations, and methylation using standard polymerase chain reaction based
methods. RESULTS: Forty-nine benign tumors did not follow a pathway similar to
that of their 31 synchronous primary cancers. For two distinct subsets of the
microsatellite unstable colorectal cancers, those with acquired methylation and
BRAF mutation, and those without methylation suggestive of an underlying germ
line mutation, the molecular changes in the majority of their synchronous benign
tumors were different from the colorectal cancer. CONCLUSIONS: These differences
suggest a stochastic process within the colon regarding the particular molecular
carcinogenic pathways followed by the synchronous tumors, rather than a 'field
defect' within the colon segments. Variability in molecular findings was present
for colorectal cancers arising from acquired methylation, as well as those
cancers suggestive of a germ line origin.
PMID- 28694924
TI - Statins redux: A re-assessment of how statins lower plasma cholesterol.
AB - Obesity associated dyslipidemia and its negative effects on the heart and blood
vessels have emerged as a major healthcare challenge around the globe. The use of
statins, potent inhibitors of hydroxyl-methyl glutaryl (HMG) Co-A reductase, a
rate-limiting enzyme in cholesterol biosynthesis, has significantly reduced the
rates of cardiovascular and general mortality in patients with coronary artery
disease. How statins lower plasma cholesterol levels presents a mechanistic
conundrum since persistent exposure to these drugs in vitro or in vivo is known
to induce overexpression of the HMG Co-A reductase gene and protein. In an
attempt to solve this mechanistic puzzle, Schonewille et al, studied detailed
metabolic parameters of cholesterol synthesis, inter-organ flux and excretion in
mice treated with 3 common statins, rosuvastatin, atorvastatin or lovastatin,
each with its unique pharmacokinetics. From the measurements of the rates of
heavy water (D2O) and [13C]-acetate incorporation into lipids, the authors
calculated the rates of whole body and organ-specific cholesterol synthesis in
control and statin-treated mice. These analyses revealed dramatic enhancement in
the rates of hepatic cholesterol biosynthesis in statin-treated mice that
concomitantly elicited lower levels of cholesterol in their plasma. The authors
have provided strong evidence to indicate that statin treatment in mice led to
induction of compensatory metabolic pathways that apparently mitigated an
excessive accumulation of cholesterol in the body. It was noted however that
changes in cholesterol metabolism induced by 3 statins were not identical. While
sustained delivery of all 3 statins led to enhanced rates of biliary excretion of
cholesterol and its fecal elimination, only atorvastatin treated mice elicited
enhanced trans-intestinal cholesterol excretion. Thus, blockade of HMGCR by
statins in mice was associated with profound metabolic adaptations that reset
their cholesterol homeostasis. The findings of Schonewille et al, deserve to be
corroborated and extended in patients in order to more effectively utilize these
important cholesterol-lowering drugs in the clinic.
PMID- 28694925
TI - Diabetes mellitus and stroke: A clinical update.
AB - Cardiovascular disease including stroke is a major complication that tremendously
increases the morbidity and mortality in patients with diabetes mellitus (DM). DM
poses about four times higher risk for stroke. Cardiometabolic risk factors
including obesity, hypertension, and dyslipidaemia often co-exist in patients
with DM that add on to stroke risk. Because of the strong association between DM
and other stroke risk factors, physicians and diabetologists managing patients
should have thorough understanding of these risk factors and management. This
review is an evidence-based approach to the epidemiological aspects,
pathophysiology, diagnostic work up and management algorithms for patients with
diabetes and stroke.
PMID- 28694927
TI - Effects of glucose-lowering agents on ischemic stroke.
AB - Diabetes mellitus (DM) is a major risk factor for cardiovascular events,
including ischemic stroke. Moreover, ischemic stroke appears to be more severe in
these patients and to be associated with less favorable outcomes. However, strict
glycemic control does not appear to reduce the risk of ischemic stroke. On the
other hand, newer glucose-lowering agents (glucagon-like peptide 1 receptor
agonists and sodium-glucose cotransporter 2 inhibitors) reduced the risk of
cardiovascular events in recent randomized, placebo-controlled trials.
Semaglutide also reduced the risk of ischemic stroke. These benefits are
independent of glucose lowering and might be due to the favorable effects of
these agents on body weight and blood pressure. Pioglitazone also reduced the
risk of recurrent stroke in patients with insulin resistance or type 2 DM but the
unfavorable safety profile limits its use. In contrast, sulfonylureas and
dipeptidyl peptidase 4 inhibitors have a neutral effect on cardiovascular
morbidity and might be less attractive options in this high-risk population.
PMID- 28694928
TI - Treatment of type 2 diabetes mellitus in the elderly.
AB - The prevalence of type 2 diabetes is expected to increase gradually with the
prolongation of population aging and life expectancy. In addition to
macrovascular and microvascular complications of elderly patients of diabetes
mellitus, geriatric syndromes such as cognitive impairment, depression, urinary
incontinence, falling and polypharmacy are also accompanied by aging. Individual
functional status in the elderly shows heterogeneity so that in these patients,
there are many unanswered questions about the management of diabetes treatment.
The goals of diabetes treatment in elderly patients include hyperglycemia and
risk factors, as in younger patients. comorbid diseases and functional
limitations of individuals should be taken into consideration when setting
treatment targets. Thus, treatment should be individualized. In the treatment of
diabetes in vulnerable elderly patients, hypoglycemia, hypotension, and drug
interactions due to multiple drug use should be avoided. Since it also affects
the ability to self-care in these patients, management of other concurrent
medical conditions is also important.
PMID- 28694926
TI - Diabetes-induced mechanophysiological changes in the small intestine and colon.
AB - The disorders of gastrointestinal (GI) tract including intestine and colon are
common in the patients with diabetes mellitus (DM). DM induced intestinal and
colonic structural and biomechanical remodeling in animals and humans. The
remodeling is closely related to motor-sensory abnormalities of the intestine and
colon which are associated with the symptoms frequently encountered in patients
with DM such as diarrhea and constipation. In this review, firstly we review DM
induced histomorphological and biomechanical remodeling of intestine and colon.
Secondly we review motor-sensory dysfunction and how they relate to intestinal
and colonic abnormalities. Finally the clinical consequences of DM-induced
changes in the intestine and colon including diarrhea, constipation, gut
microbiota change and colon cancer are discussed. The final goal is to increase
the understanding of DM-induced changes in the gut and the subsequent clinical
consequences in order to provide the clinicians with a better understanding of
the GI disorders in diabetic patients and facilitates treatments tailored to
these patients.
PMID- 28694929
TI - Statin use and cognitive function in middle-aged adults with type 1 diabetes.
AB - AIM: To test associations between statin use and cognitive impairment in adults
with childhood-onset type 1 diabetes (T1D). METHODS: In 2010-13, n = 108 middle
aged participants from ongoing observational Pittsburgh Epidemiology of Diabetes
Complications Study underwent neurocognitive assessment (mean age and T1D
duration of 49 and 41 years, respectively). All were diagnosed with childhood
onset (i.e., prior to age 18) T1D between 1950 and 1980 and were seen within one
year of diagnosis at Children's Hospital of Pittsburgh. Self-reported statin use
(yes/no and if yes, name of statin) was collected biennially from parent study
baseline (1986-1988) to time of neurocognitive testing. Logistic regression
models tested associations between statin use groups and cognitive impairment
(defined as having two or more cognitive test scores 1.5SD or worse than
published norms) while linear regression models tested associations between
statin use groups and cognitive domain z-scores (domains: Verbal IQ, memory,
executive function, psychomotor speed, and visuo-construction). All models
controlled for education and age. To address confounding by indication, models
were repeated using a propensity score for statin use. RESULTS: Of the 108
participants, 51 reported never using statins. Median duration of statin use
among the 57 ever users was 6 years. These 57 ever statin users were split to
create two groups (<= or > median years of statin use): 1-6 years (n = 25), and 7
12 years (n = 32). Compared with never users, using statins 1-6 years tripled the
odds of cognitive impairment (OR = 3.16; 95%CI: 0.93-10.72; P = 0.06) and using
statins 7-12 years almost quintupled the odds of cognitive impairment (OR = 4.84;
95%CI: 1.63-14.44; P = 0.005). Compared with never users, using statins 1-6 or 7
12 years was related to worse performance in the memory domain (beta = -0.52; P =
0.003, and -0.39; P = 0.014, respectively). Adjusting for coronary artery
disease, low density lipoprotein cholesterol, and Apo E4 status did not
substantially alter results, and none of these covariates were significantly
related to cognitive outcomes (all P > 0.05). Propensity score analyses support
that associations between poor cognitive outcomes and statin use were not due
merely to confounding by indication. CONCLUSION: Statin use was associated with
cognitive impairment, particularly affecting memory, in these middle-aged adults
with childhood-onset T1D, whom at this age, should not yet manifest age-related
memory deficits.
PMID- 28694930
TI - Risk factors for low high-density lipoprotein among Asian Indians in the United
States.
AB - AIM: To examine the differences in metabolic risk factors (RFs) by gender in the
Asian Indian (AI) population in the United States. METHODS: Using cross-sectional
data from 1038 randomly selected Asian Indians, we investigated the relationship
between metabolic syndrome (MetS) RFs, cardiovascular disease, and diabetes.
RESULTS: A greater percent of women in this group had increased waist
circumference and low high density lipoprotein (HDL) levels than men, but AI
males had increased blood glucose, increased blood pressure, and increased
triglycerides compared to females. Those individuals who met the MetS criteria
had increased cardiovascular disease. One of the biggest single RFs for
cardiovascular disease and diabetes reported in the literature for AIs is low
HDL. CONCLUSION: Our results show that lack of knowledge about diabetes, low
physical activity, increased body mass index, and age were the factors most
significantly correlated with low HDL in this population. Future studies and
prospective trials are needed to further elucidate causes of the MetS and
diabetes in AIs.
PMID- 28694931
TI - Interleukin-18 polymorphism as an inflammatory index in metabolic syndrome: A
preliminary study.
AB - AIM: To assess circulatory levels of interleukin-18 (IL-18) and determine whether
the presence of IL-18 promoter polymorphism influences metabolic syndrome
phenotypes. METHODS: This study recruited one hundred and eighty individuals
divided into three groups with sixty subjects each as: Normal weight (18.0-22.9
kg/m2), overweight (23.0-25.9 kg/m2) and obese (> 26.0 kg/m2) according to South
Asian criteria of BMI. Fasting blood glucose (FBG), Lipid profile, insulin, IL-18
and tumor necrosis factor (TNF)alpha were measured using ELISA kits, whereas low
density lipoprotein (LDL)-cholesterol, insulin resistance (HOMA-IR) and insulin
sensitivity (QUICKI) were calculated. The body fat percentage (BF) was measured
through bioelectrical impedance analysis; waist and hip circumference were
measured. Genotyping of IL-18 -607 C/A polymorphism was performed by using tetra
primer amplification refractory mutation system. Student t test, One-way analysis
of variance, Hardy-Weinberg equilibrium, Pearson's chi2 test and Pearson's
correlation were used, where a P value < 0.05 was considered significant.
RESULTS: In an aged matched study, obese subjects showed higher levels of FBG,
cholesterol, triglycerides and LDL levels as compared to normal weight (P <
0.001). Highest levels of IL-18 and TNF levels were also seen in obese subjects
(IL-18: 58.87 +/- 8.59 ng/L) (TNF: 4581.93 +/- 2132.05 pg/mL). The percentage of
IL-18 -607 A/A polymorphism was higher in overweight and obese subjects vs normal
weight subjects (P < 0.001). Moreover, subjects with AA genotype had a higher BF,
insulin resistance, TNFalpha and IL-18 levels when compared with subjects with AC
(heterozygous) or CC (wild type) genotypes. However, we did not find any
difference in the lipid profile between three subgroups. CONCLUSION: This
preliminary data suggests that IL-18 polymorphism affects IL-18 levels that might
cause low grade inflammation, further exacerbated by increased TNFalpha. All
these increase the susceptibility to develop MetS. Further studies are required
to validate our findings.
PMID- 28694932
TI - Nuclear Magnetic Resonance (NMR) Study for the Detection and Quantitation of
Cholesterol in HSV529 Therapeutic Vaccine Candidate.
AB - This study describes the NMR-based method to determine the limit of quantitation
(LOQ) and limit of detection (LOD) of cholesterol, a process-related impurity in
the replication-deficient Herpes Simplex Virus (HSV) type 2 candidate vaccine
HSV529. Three signature peaks from the 1D 1H NMR of a cholesterol reference
spectrum were selected for the identification of cholesterol. The LOQ for a
cholesterol working standard was found to be 1 MUg/mL, and the LOD was found to
be 0.1 MUg/mL. The identity of cholesterol, separated from the formulation of
growth supplement by thin layer chromatography (TLC), was confirmed by 1D 1H NMR
and 2D 1H-13C HSQC NMR. The three signature peaks of cholesterol were detected
only in a six-times concentrated sample of HSV529 candidate vaccine sample and
not in the single dose HSV529 vaccine sample under similar experimental
conditions. Taken together, the results demonstrated that NMR is a direct method
that can successfully identify and quantify cholesterol in viral vaccine samples,
such as HSV529, and as well as in the growth supplement used during the upstream
stages of HSV529 manufacturing.
PMID- 28694933
TI - Are the Symptoms of Parkinsonism Cortical in Origin?
AB - We present three reasons to suspect that the major deleterious consequence of
dopamine loss from the striatum is a cortical malfunction. We suggest that it is
cortex, rather than striatum, that should be considered as the source of the
debilitating symptoms of Parkinson's disease (PD) since:1.Cortical synapses onto
striatal dendritic spines are lost in PD.2.All known treatments of the symptoms
of PD disrupt beta oscillations. Oscillations that are also disrupted following
antidromic activation of cortical neurons.3.The final output of basal ganglia
directly modulates thalamic connections to layer I of frontal cortical areas,
regions intimately associated with motor behaviour. These three reasons combined
with evidence that the current summary diagram of the basal ganglia involvement
in PD is imprecise at best, suggest that a re-orientation of the treatment
strategies towards cortical, rather than striatal malfunction, is overdue.
PMID- 28694934
TI - Regulation of Metabolic Pathways by MarR Family Transcription Factors.
AB - Bacteria have evolved sophisticated mechanisms for regulation of metabolic
pathways. Such regulatory circuits ensure that anabolic pathways remain repressed
unless final products are in short supply and that catabolic enzymes are not
produced in absence of their substrates. The precisely tuned gene activity
underlying such circuits is in the purview of transcription factors that may bind
pathway intermediates, which in turn modulate transcription factor function and
therefore gene expression. This review focuses on the role of ligand-responsive
MarR family transcription factors in controlling expression of genes encoding
metabolic enzymes and the mechanisms by which such control is exerted. Prospects
for exploiting these transcription factors for optimization of gene expression
for metabolic engineering and for the development of biosensors are considered.
PMID- 28694935
TI - The potential of ixazomib, a second-generation proteasome inhibitor, in the
treatment of multiple myeloma.
AB - The therapeutic armamentarium for multiple myeloma has recently benefited from
the addition of several new agents (including second-generation proteasome
inhibitors, monoclonal antibodies and histone deacetylase inhibitors). This
review will focus on ixazomib, an orally bioavailable second-generation
proteasome inhibitor. Specifically, we will review the preclinical data, clinical
trial experience, potential indications as well as unanswered questions
pertaining to this new agent in multiple myeloma.
PMID- 28694936
TI - Stipules in Apocynaceae: an ontogenetic perspective.
AB - Stipules are leaf structures common in many groups of plants that can take a
variety of forms. In Gentianales, interpetiolar stipules are considered a
synapomorphy of Rubiaceae; however, some reports in the literature refer to their
presence in other families. The goal of this study was to analyze the development
of leaf primordia to investigate the possible presence of reduced or modified
stipules in Apocynaceae. Shoot apices of 12 genera were analyzed under light and
scanning electron microscopy comparatively with one species of Rubiaceae. Early
in their development, leaf primordia form two lateral expansions at the base of
the petiole (stipules) that give rise to colleters in 11 of the 12 genera of
Apocynaceae studied, similarly to the Rubiaceae species. The basal genera have
pairs of stipules modified into colleters positioned laterally to the petiole,
while other species belonging to the derived subfamilies have interpetiolar
stipules that each project towards the opposite stipule and merge, forming a
sheathing stipule and from this arc the interpetiolar colleters originate. The
ontogenetic study proved for the first time that Apocynaceae is a stipulate
family whose stipules are modified into colleters and their absence might be a
secondary loss, changing the interpretation of stipule evolution in Gentianales.
PMID- 28694937
TI - Semiconductor-driven "turn-off" surface-enhanced Raman scattering spectroscopy:
application in selective determination of chromium(vi) in water.
AB - Semiconductor materials have been successfully used as surface-enhanced Raman
scattering (SERS)-active substrates, providing SERS technology with a high
flexibility for application in a diverse range of fields. Here, we employ a dye
sensitized semiconductor system combined with semiconductor-enhanced Raman
spectroscopy to detect metal ions, using an approach based on the "turn-off" SERS
strategy that takes advantage of the intrinsic capacity of the semiconductor to
catalyze the degradation of a Raman probe. Alizarin red S (ARS)-sensitized
colloidal TiO2 nanoparticles (NPs) were selected as an example to show how
semiconductor-enhanced Raman spectroscopy enables the determination of Cr(vi) in
water. Firstly, we explored the SERS mechanism of ARS-TiO2 complexes and found
that the strong electronic coupling between ARS and colloidal TiO2 NPs gives rise
to the formation of a ligand-to-metal charge-transfer (LMCT) transition,
providing a new electronic transition pathway for the Raman process. Secondly,
colloidal TiO2 nanoparticles were used as active sites to induce the self
degradation of the Raman probe adsorbed on their surfaces in the presence of
Cr(vi). Our data demonstrate the potential of ARS-TiO2 complexes as a SERS-active
sensing platform for Cr(vi) in an aqueous solution. Remarkably, the method
proposed in this contribution is relatively simple, without requiring complex
pretreatment and complicated instruments, but provides high sensitivity and
excellent selectivity in a high-throughput fashion. Finally, the ARS-TiO2
complexes are successfully applied to the detection of Cr(vi) in environmental
samples. Thus, the present work provides a facile method for the detection of
Cr(vi) in aqueous solutions and a viable application for semiconductor-enhanced
Raman spectroscopy based on the chemical enhancement they contribute.
PMID- 28694938
TI - Accelerated Hantzsch electrospray synthesis with temporal control of reaction
intermediates.
AB - Complex chemical reactions can occur in electrosprayed droplets on the
millisecond time scale. The Hantzsch synthesis of 1,4-dihydropyridines was
studied in this way using on-line mass spectral analysis to optimize conditions
and characterize the product mixture. Changing the distance between the nanospray
source and the MS inlet allowed exploration of reaction progress as a function of
droplet time-of-flight. Desolvation of the charged microdroplets is associated
with transformation from starting material to intermediates and eventually to
product as the distance is increased. Results of the on-line experiments require
a termination step that discontinuously completes the desolvation process and
allows the generated gaseous ions to be used to characterize the state of the
system at a particular time. The intermediates seen correspond to those known to
occur in the bulk solution-phase reaction. Off-line collection of the sprayed
reaction mixture allowed the recovery of 250 mg h-1 of desired reaction product
from a single sprayer, permitting characterization by NMR and other standard
methods. A thin film version of the accelerated reaction is described and it
could be controlled through the temperature of the collection surface.
PMID- 28694939
TI - Metallic behaviour of acid doped highly conductive polymers.
AB - Conductive polymers such as poly(3,4-ethylenedioxythiophene) (PEDOT) are used in
a wide range of applications as transparent electrodes, hole injecting layers or
thermoelectric materials for room-temperature applications. However, progress is
needed to enhance the electrical conductivities of the materials and to provide
understanding about their structure-transport relationships. This work presents
the synthesis of highly conductive PEDOT-based polymers using iron(iii)
trifluoromethanesulfonate as oxidant for the first time. The metallic behaviour
of the polymer is revealed by conductivity monitoring from 3 to 300 K. The
electrical conductivity is further improved (to 2273 S cm-1) using acids, leading
to a positive temperature coefficient of resistivity at an unprecedented 45.5%
oxidation state. X-ray photoemission spectroscopy (XPS) and time of flight
secondary ion mass spectrometry (ToF-SIMS) analyses demonstrate a complete
replacement of the trifluoromethanesulfonate anions by hydrogen sulphate counter
ions. This substitution results in an increased concentration of charge carriers
(measured in organic electrochemical transistors) along with an enhancement of
the mean size of crystalline domains, highlighted by small and wide angle X-ray
scattering (SAXS/WAXS), which explains the 80% increase of electrical
conductivity.
PMID- 28694940
TI - Tailored chondroitin sulfate glycomimetics via a tunable multivalent scaffold for
potentiating NGF/TrkA-induced neurogenesis.
AB - The challenges inherent in the synthesis of large glycosaminoglycan (GAG)
polysaccharides have made chemically accessible multivalent glycoligands a
valuable tool in the field of GAG mimetics. However, the difficulty of
positioning sulfated sugar motifs at desired sites has hindered efforts to
precisely tailor their biofunctions. Here, we achieved precise orientation of
sulfated disaccharide motifs by taking advantage of a structurally well-defined
polyproline scaffold, and describe systematic explorations into the importance of
the spatial arrangement of sulfated sugars along the scaffold backbone in
designing multivalent glycoligands. Our protein binding studies demonstrate that
the specific conformational display of pendant sugars is central to direct their
multivalent interactions with NGF. By employing computational modeling and
cellular studies, we have further applied this approach to engineer NGF-mediated
signaling by regulating the NGF/TrkA complexation process, leading to enhanced
neuronal differentiation and neurite outgrowth of PC12 cells. Our findings offer
a promising strategy for the pinpoint engineering of GAG-mediated biological
processes and a novel method of designing new therapeutic agents that are highly
specific to GAG-associated disease.
PMID- 28694941
TI - Annihilation electrogenerated chemiluminescence of mixed metal chelates in
solution: modulating emission colour by manipulating the energetics.
AB - We demonstrate the mixed annihilation electrogenerated chemiluminescence of
tris(2,2'-bipyridine)ruthenium(ii) with various cyclometalated iridium(iii)
chelates. Compared to mixed ECL systems comprising organic luminophores, the
absence of T-route pathways enables effective predictions of the observed ECL
based on simple estimations of the exergonicity of the reactions leading to
excited state production. Moreover, the multiple, closely spaced reductions and
oxidations of the metal chelates provide the ability to finely tune the
energetics and therefore the observed emission colour. Distinct emissions from
multiple luminophores in the same solution are observed in numerous systems. The
relative intensity of these emissions and the overall emission colour are
dependent on the particular oxidized and reduced species selected by the applied
electrochemical potentials. Finally, these studies offer insights into the
importance of electronic factors in the question of whether the reduced or
oxidized partner becomes excited in annihilation ECL.
PMID- 28694942
TI - "Self-repairing" nanoshell for cell protection.
AB - Self-repair is nature's way of protecting living organisms. However, most single
cells are inherently less capable of self-repairing, which greatly limits their
wide applications. Here, we present a self-assembly approach to create a
nanoshell around the cell surface using nanoporous biohybrid aggregates. The
biohybrid shells present self-repairing behaviour, resulting in high activity and
extended viability of the encapsulated cells (eukaryotic and prokaryotic cells)
in harsh micro-environments, such as under UV radiation, natural toxin invasion,
high-light radiation and abrupt pH-value changes. Furthermore, an interaction
mechanism is proposed and studied, which is successful to guide design and
synthesis of self-repairing biohybrid shells using different bioactive molecules.
PMID- 28694943
TI - Ion-mediated conformational switches.
AB - Molecular switches are ubiquitous in Nature and provide the basis of many forms
of transport and signalling. Single synthetic molecules that change conformation,
and thus function, reversibly in a stimulus-dependent manner are of great
interest not only to chemists but society in general; myriad applications exist
in storage, display, sensing and medicine. Here we describe recent developments
in the area of ion-mediated switching.
PMID- 28694944
TI - Integration of an anti-tumor drug into nanocrystalline assemblies for sustained
drug release.
AB - Delicate mesoscopic architectures, bearing complex forms with multiple hierarchy
levels, lead to significant functions in biogenic minerals. Herein, a bio
inspired approach was developed to fabricate comet-shaped assemblies of an anti
tumor drug - 10-hydroxycamptothecin (HCPT). The anti-solvent co-precipitation of
HCPT and the excipient - PEG-b-PLGA - within the emulsifier leads to the
immediate nucleation of comet bundles, followed by a secondary nucleation to
generate the comet head, which is an assembly of nanofibers aligned almost in
parallel. The continuous manufacturing furnishes drug-excipient hybrid particles
with high drug-loading and a sustained drug release profile. This simple and
efficient bio-inspired approach led to a promising sustained local drug delivery
system, and could be extended to the fabrication of other functional organic
materials bearing mesoscopic structural units.
PMID- 28694945
TI - Inherently chiral electrodes: the tool for chiral voltammetry.
AB - 2,2'-Bis[2-(5,2'-bithienyl)]-3,3'-bithianaphthene oligomers are a model case of
electroactive films endowed with "inherent chirality", originating from a
stereogenic element coinciding with the whole electroactive backbone, thus
resulting in impressive manifestations. This study highlights their applicative
potentialities as low-cost and easy-to-prepare artificial enantiopure electrode
surfaces, which display an unprecedented ability to pronouncedly separate
voltammetry peaks of enantiomers of quite different chiral probes of applicative
interest, concurrently with linear dynamic ranges for peak currents, affording
enantiomer excess determination. Thus inherently chiral enantiopure electrodes
can indeed be regarded as a key to chiral voltammetry.
PMID- 28694946
TI - Design of an intelligent sub-50 nm nuclear-targeting nanotheranostic system for
imaging guided intranuclear radiosensitization.
AB - Clinically applied chemotherapy and radiotherapy is sometimes not effective due
to the limited dose acting on DNA chains resident in the nuclei of cancerous
cells. Herein, we develop a new theranostic technique of "intranuclear
radiosensitization" aimed at directly damaging the DNA within the nucleus by a
remarkable synergetic chemo-/radiotherapeutic effect based on intranuclear
chemodrug-sensitized radiation enhancement. To achieve this goal, a sub-50 nm
nuclear-targeting rattle-structured upconversion core/mesoporous silica
nanotheranostic system was firstly constructed to directly transport the
radiosensitizing drug Mitomycin C (MMC) into the nucleus for substantially
enhanced synergetic chemo-/radiotherapy and simultaneous magnetic/upconversion
luminescent (MR/UCL) bimodal imaging, which can lead to efficient cancer
treatment as well as multi-drug resistance circumvention in vitro and in vivo. We
hope the technique of intranuclear radiosensitization along with the design of
nuclear-targeting nanotheranostics will contribute greatly to the development of
cancer theranostics as well as to the improvement of the overall therapeutic
effectiveness.
PMID- 28694947
TI - Fluorescent/phosphorescent dual-emissive conjugated polymer dots for hypoxia
bioimaging.
AB - A kind of fluorescent/phosphorescent dual-emissive conjugated polyelectrolyte has
been prepared by introducing phosphorescent platinum(ii) porphyrin (O2-sensitive)
into a fluorene-based conjugated polyelectrolyte (O2-insensitive), which can form
ultrasmall conjugated polymer dots (FP-Pdots) in the phosphate buffer solution
(PBS) via self-assembly caused by their amphiphilic structures with hydrophobic
backbones and hydrophilic side chains. These FP-Pdots can exhibit an excellent
ratiometric luminescence response to O2 content with high reliability and full
reversibility for measuring oxygen levels, and the excellent intracellular
ratiometric O2 sensing properties of the FP-Pdots nanoprobe have also been
confirmed by the evident change in the Ired/Iblue ratio values in living cells
cultured at different O2 concentrations. To confirm the reliability of the O2
sensing measurements of the FP-Pdots nanoprobe, O2 quenching experiments based on
lifetime measurements of phosphorescence from Pt(ii) porphyrin moieties have also
been carried out. Utilizing the sensitivity of the long phosphorescence lifetime
from Pt(ii) porphyrins to oxygen, the FP-Pdots have been successfully applied in
time-resolved luminescence imaging of intracellular O2 levels, including
photoluminescence lifetime imaging and time-gated luminescence imaging, which
will evidently improve the sensing sensitivity and reliability. Finally, in vivo
oxygen sensing experiments were successfully performed by luminescence imaging of
tumor hypoxia in nude mice.
PMID- 28694948
TI - Palladium: a future key player in the nanomedical field?
AB - Metal nanostructures offer invaluable possibilities for targeted drug delivery,
detection/diagnosis and imaging. Whereas iron, gold, silver and platinum
nanoarchitectures have largely dominated this field to date, several hurdles
impede the widespread application of those nanopharmaceuticals in a clinical
context. Therefore, technologies based on alternative metals are now being
evaluated for their potential in medical applications. Palladium nanostructures
are characterized by remarkable catalytic and optical properties. However, until
recently, very few studies have taken advantage of these unique characteristics
for applications in the biomedical field. Very recently, palladium nanostructures
have been reported as prodrug activator, as photothermal agents and for anti
cancer/anti-microbial therapy. With only a handful of reports available, the
pharmaceutical applications of palladium nanostructures reviewed here are in
their infancy. Yet their interesting performance and toxicity profiles may
qualify them as future key players in the nanomedical field.
PMID- 28694949
TI - Molecular engineering of mechanophore activity for stress-responsive polymeric
materials.
AB - Force reactive functional groups, or mechanophores, have emerged as the basis of
a potential strategy for sensing and countering stress-induced material failure.
The general utility of this strategy is limited, however, because the levels of
mechanophore activation in the bulk are typically low and observed only under
large, typically irreversible strains. Strategies that enhance activation are
therefore quite useful. Molecular-level design principles by which to engineer
enhanced mechanophore activity are reviewed, with an emphasis on quantitative
structure-activity studies determined for a family of gem-dihalocyclopropane
mechanophores.
PMID- 28694950
TI - Steric effects and quantum interference in the inelastic scattering of NO(X) +
Ar.
AB - Rotationally inelastic collisions of NO(X) with Ar are investigated in
unprecedented detail using state-to-state, crossed molecular beam experiments.
The NO(X) molecules are selected in the Omega = 0.5, j = 0.5, f state and then
oriented such that either the 'N' or 'O' end of the molecule is directed towards
the incoming Ar atom. Velocity map ion imaging is then used to probe the
scattered NO molecules in well-defined quantum states. We show that the fully
quantum state-resolved differential steric asymmetry, which quantifies how the
relative efficiency for scattering off the 'O' and the 'N' ends of the molecule
varies with scattering angle, is strongly affected by quantum interference.
Significant changes in both integral and differential cross sections are found
depending on whether collisions occur with the N or O ends of the molecule. The
results are well accounted for by rigorous quantum mechanical calculations, in
contrast to both classical trajectory calculations and more simplistic models
that provide, at best, an incomplete picture of the dynamics.
PMID- 28694951
TI - Large ring-forming alkylations provide facile access to composite macrocycles.
AB - Macrocyclic compounds have potential to enable drug discovery for protein targets
with extended, solvent-exposed binding sites. Crystallographic structures of
peptides bound at such sites show strong surface complementarity and frequent
aromatic side-chain contacts. In an effort to capture these features in
stabilized small molecules, we describe a method to convert linear peptides into
constrained macrocycles based upon their aromatic content. Designed templates
initiate the venerable Friedel-Crafts alkylation to form large rings efficiently
at room temperature - routinely within minutes - and unimpeded by polar
functional groups. No protecting groups, metals, or air-free techniques are
required. Regiochemistry can be tuned electronically to explore diverse
macrocycle connectivities. Templates with additional reaction capabilities can
further manipulate macrocycle structure. The chemistry lays a foundation to
extend studies of how the size, shape and constitution of peptidyl macrocycles
correlate with their pharmacological properties.
PMID- 28694952
TI - Enhanced intersystem crossing in core-twisted aromatics.
AB - We describe the design, bottom-up synthesis and X-ray single crystal structure of
systematically twisted aromatics 1c and 2d for efficient intersystem crossing.
Steric congestion at the cove region creates a nonplanar geometry that induces a
significant yield of triplet excited states in the electron-poor core-twisted
aromatics 1c and 2d. A systematic increase in the number of twisted regions in 1c
and 2d results in a concomitant enhancement in the rate and yield of intersystem
crossing, monitored using femtosecond and nanosecond transient absorption
spectroscopy. Time-resolved absorption spectroscopic measurements display
enhanced triplet quantum yields (PhiT = 10 +/- 1% for 1c and PhiT = 30 +/- 2% for
2d) in the twisted aromatics when compared to a negligible PhiT (<1%) in the
planar analog 3c. Twist-induced spin-orbit coupling via activated out-of-plane C
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vibrations can facilitate the formation of triplet excited states in twisted
aromatics 1c and 2d, in contrast to the negligible intersystem crossing in the
planar analog 3c. The ease of synthesis, high solubility, access to triplet
excited states and strong electron affinity make such imide functionalized core
twisted aromatics desirable materials for organic electronics such as solar
cells.
PMID- 28694953
TI - Halogen bonded Borromean networks by design: topology invariance and metric
tuning in a library of multi-component systems.
AB - A library of supramolecular anionic networks showing Borromean interpenetration
has been prepared by self-assembly of crypt-222, several metal or ammonium
halides, and five bis-homologous alpha,omega-diiodoperfluoroalkanes. Halogen
bonding has driven the formation of these anionic networks. Borromean
entanglement has been obtained starting from all the four used cations, all the
three used anions, but only two of the five used diiodoperfluoroalkanes. As the
change of the diiodoperfluoroalkane, the cation, or the anion has a different
relative effect on the metrics and bondings of the self-assembled systems, it can
be generalized that bonding, namely energetic, features play here a less
influential role than metric features in determining the topology of the prepared
tetra-component cocrystals. This conclusion may hold true for other multi
component systems and may function as a general heuristic principle when pursuing
the preparation of multi-component systems having the same topology but different
composition.
PMID- 28694954
TI - Chiral hemicucurbit[8]uril as an anion receptor: selectivity to size, shape and
charge distribution.
AB - A novel eight-membered macrocycle of the hemicucurbit[n]uril family, chiral (all
R)-cyclohexanohemicucurbit[8]uril (cycHC[8]) ?The name
cyclohexylhemicucurbituril, previously used for these macrocycles, is changed in
accordance with the IUPAC nomenclature for fused cycles, as the cyclohexane
substituents are fused with the parent hemicucurbituril. binds anions in a purely
protic solvent with remarkable selectivity. The cycHC[8] portals open and close
to fully encapsulate anions in a 1 : 1 ratio, resembling a molecular Pac-ManTM.
Comprehensive gas, solution and solid phase studies prove that the binding is
governed by the size, shape and charge distribution of the bound anion. Gas phase
studies show an order of SbF6- ~ PF6- > ReO4- > ClO4- > SCN- > BF4- > HSO4- >
CF3SO3- for anion complexation strength. An extensive crystallographic study
reveals the preferred orientations of the anions within the octahedral cavity of
cycHC[8] and highlights the importance of the size- and shape-matching between
the anion and the receptor cavity. The solution studies show the strongest
binding of the ideally fitting SbF6- anion, with an association constant of 2.5 *
105 M-1 in pure methanol. The symmetric, receptor cavity-matching charge
distribution of the anions results in drastically stronger binding than in the
case of anions with asymmetric charge distribution. Isothermal titration
calorimetry (ITC) reveals the complexation to be exothermic and enthalpy-driven.
The DFT calculations and VT-NMR studies confirmed that the complexation proceeds
through a pre-complex formation while the exchange of methanol solvent with the
anion is the rate-limiting step. The octameric cycHC[8] offers a unique example
of template-controlled design of an electroneutral host for binding large anions
in a competitive polar solvent.
PMID- 28694955
TI - Spin-crossover and high-spin iron(ii) complexes as chemical shift 19F magnetic
resonance thermometers.
AB - The potential utility of paramagnetic transition metal complexes as chemical
shift 19F magnetic resonance (MR) thermometers is demonstrated. Further, spin
crossover FeII complexes are shown to provide much higher temperature sensitivity
than do the high-spin analogues, owing to the variation of spin state with
temperature in the former complexes. This approach is illustrated through a
series of FeII complexes supported by symmetrically and asymmetrically
substituted 1,4,7-triazacyclononane ligand scaffolds bearing 3-fluoro-2-picolyl
derivatives as pendent groups (L x ). Variable-temperature magnetic
susceptibility measurements, in conjunction with UV-vis and NMR data, show
thermally-induced spin-crossover for [Fe(L1)]2+ in H2O, with T1/2 = 52(1)
degrees C. Conversely, [Fe(L2)]2+ remains high-spin in the temperature range 4-61
degrees C. Variable-temperature 19F NMR spectra reveal the chemical shifts of
the complexes to exhibit a linear temperature dependence, with the two peaks of
the spin-crossover complex providing temperature sensitivities of +0.52(1) and
+0.45(1) ppm per degrees C in H2O. These values represent more than two-fold
higher sensitivity than that afforded by the high-spin analogue, and ca. 40-fold
higher sensitivity than diamagnetic perfluorocarbon-based thermometers. Finally,
these complexes exhibit excellent stability in a physiological environment, as
evidenced by 19F NMR spectra collected in fetal bovine serum.
PMID- 28694956
TI - Highly near-IR emissive ytterbium(iii) complexes with unprecedented quantum
yields.
AB - The design of highly near-infrared (NIR) emissive lanthanide (Ln) complexes is
challenging, owing to the lack of molecular systems with a high sensitization
efficiency and the difficulty of achieving a large intrinsic quantum yield.
Previous studies have reported success in optimizing individual factors and
achieving high overall quantum yields, with the best yield being 12% for Yb(iii).
Herein we report a series of highly NIR emissive Yb complexes, in which the Yb is
sandwiched between an octafluorinated porphyrinate antenna ligand and a
deuterated Klaui ligand, which allowed optimization of two factors in the same
system, and one of the complexes had an unprecedented quantum yield of 63%
(estimated uncertainty 15%) in CD2Cl2 with a long lifetime (tauobs) of 714 MUs.
Systematic analysis of the structure-photophysical properties relationship
suggested that porphyrinates are effective antenna ligands with a sensitization
efficiency up to ca. 100% and that replacement of the high-energy C-H oscillators
in porphyrinate and Klaui ligands significantly improves the intrinsic quantum
yield up to 75% (tauobs/taurad), both of which contribute to enhancing the NIR
emission intensity of Yb(iii) up to 25-fold. Besides the high luminescence
efficiency, these Yb complexes have other attractive features such as excitation
in the visible range and large extinction coefficients which make these Yb(iii)
complexes outstanding optical materials in the NIR region.
PMID- 28694957
TI - Johann Joseph on Geometrical-Optical Illusions: A Translation and Commentary.
AB - The term geometrical-optical illusions was coined by Johann Joseph Oppel (1815
1894) in 1855 in order to distinguish spatial distortions of size and orientation
from the broader illusions of the senses. We present a translation of Oppel's
article and a commentary on the material described in it. Oppel did much more
than give a name to a class of visual spatial distortions. He examined a variety
of figures and phenomena that were precursors of later, named illusions, and
attempted to quantify and interpret them.
PMID- 28694958
TI - Subjective Ratings of Beauty and Aesthetics: Correlations With Statistical Image
Properties in Western Oil Paintings.
AB - For centuries, oil paintings have been a major segment of the visual arts. The
JenAesthetics data set consists of a large number of high-quality images of oil
paintings of Western provenance from different art periods. With this database,
we studied the relationship between objective image measures and subjective
evaluations of the images, especially evaluations on aesthetics (defined as
artistic value) and beauty (defined as individual liking). The objective measures
represented low-level statistical image properties that have been associated with
aesthetic value in previous research. Subjective rating scores on aesthetics and
beauty correlated not only with each other but also with different combinations
of the objective measures. Furthermore, we found that paintings from different
art periods vary with regard to the objective measures, that is, they exhibit
specific patterns of statistical image properties. In addition, clusters of
participants preferred different combinations of these properties. In conclusion,
the results of the present study provide evidence that statistical image
properties vary between art periods and subject matters and, in addition, they
correlate with the subjective evaluation of paintings by the participants.
PMID- 28694959
TI - Does Language Influence the Vertical Representation of Auditory Pitch and
Loudness?
AB - Higher frequency and louder sounds are associated with higher positions whereas
lower frequency and quieter sounds are associated with lower locations. In
English, "high" and "low" are used to label pitch, loudness, and spatial
verticality. By contrast, different words are preferentially used, in Catalan and
Spanish, for pitch (high: "agut/agudo"; low: "greu/grave") and for
loudness/verticality (high: "alt/alto"; low: "baix/bajo"). Thus, English and
Catalan/Spanish differ in the spatial connotations for pitch. To analyze the
influence of language on these crossmodal associations, a task was conducted in
which English and Spanish/Catalan speakers had to judge whether a tone was higher
or lower (in pitch or loudness) than a reference tone. The response buttons were
located at crossmodally congruent or incongruent positions with respect to the
probe tone. Crossmodal correspondences were evidenced in both language groups.
However, English speakers showed greater effects for pitch, suggesting an
influence of linguistic background.
PMID- 28694960
TI - Tri-layered composite plug for the repair of osteochondral defects: in vivo study
in sheep.
AB - Cartilage defects are a source of pain, immobility, and reduced quality of life
for patients who have acquired these defects through injury, wear, or disease.
The avascular nature of cartilage tissue adds to the complexity of cartilage
tissue repair or regeneration efforts. The known limitations of using autografts,
allografts, or xenografts further add to this complexity. Autologous chondrocyte
implantation or matrix-assisted chondrocyte implantation techniques attempt to
introduce cultured cartilage cells to defect areas in the patient, but clinical
success with these are impeded by the avascularity of cartilage tissue.
Biodegradable, synthetic scaffolds capable of supporting local cells and
overcoming the issue of poor vascularization would bypass the issues of current
cartilage treatment options. In this study, we propose a biodegradable, tri
layered (poly(glycolic acid) mesh/poly(l-lactic acid)-colorant tidemark
layer/collagen Type I and ceramic microparticle-coated poly(l-lactic acid)
poly(epsilon-caprolactone) monolith) osteochondral plug indicated for the repair
of cartilage defects. The porous plug allows the continual transport of bone
marrow constituents from the subchondral layer to the cartilage defect site for a
more effective repair of the area. Assessment of the in vivo performance of the
implant was conducted in an ovine model (n = 13). In addition to a control group
(no implant), one group received the implant alone (Group A), while another group
was supplemented with hyaluronic acid (0.8 mL at 10 mg/mL solution; Group B).
Analyses performed on specimens from the in vivo study revealed that the implant
achieves cartilage formation within 6 months. No adverse tissue reactions or
other complications were reported. Our findings indicate that the porous
biocompatible implant seems to be a promising treatment option for the cartilage
repair.
PMID- 28694961
TI - Equity in HTA: what doesn't get measured, gets marginalised.
AB - When making recommendations about the public funding of new health technologies,
policy makers typically pay close attention to quantitative evidence about the
comparative effectiveness, cost effectiveness and budget impact of those
technologies - what we might call "efficiency" criteria. Less attention is paid,
however, to quantitative evidence about who gains and who loses from these public
expenditure decisions, and whether those who gain are better or worse off than
the rest of the population in terms of their health - what we might call "equity"
criteria. Two studies recently published in this journal by Shmueli and
colleagues suggest that this efficiency-oriented imbalance in the use of
quantitative evidence may have unfortunate consequences - as the old adage goes:
"what gets measured, gets done". The first study, by Shmueli, Golan, Paolucci and
Mentzakis, found that health policy makers in Israel think equity considerations
are just as important as efficiency considerations - at least when it comes to
making hypothetical technology funding decisions in a survey. By contrast, the
second study - by Shmueli alone - found that efficiency rules the roost when it
comes to making real decisions about health technology funding in Israel. Both
studies have limitations and potential biases, and more research is needed using
qualitative methods and more nuanced survey designs to determine precisely which
kinds of equity consideration decision makers think are most important and why
these considerations do not appear to be given much weight in decision making.
However, the basic overall finding from the two studies seems plausible and
important. It suggests that health technology funding bodies need to pay closer
attention to equity considerations, and to start making equity a quantitative
endpoint of health technology assessment using the methods of equity-informative
economic evaluation that are now available.
PMID- 27635217
TI - The developmental transcriptome of contrasting Arctic charr ( Salvelinus alpinus)
morphs.
AB - Species and populations with parallel evolution of specific traits can help
illuminate how predictable adaptations and divergence are at the molecular and
developmental level. Following the last glacial period, dwarfism and specialized
bottom feeding morphology evolved rapidly in several landlocked Arctic charr
Salvelinus alpinus populations in Iceland. To study the genetic divergence
between small benthic morphs and limnetic morphs, we conducted RNA-sequencing
charr embryos at four stages in early development. We studied two stocks with
contrasting morphologies: the small benthic (SB) charr from Lake Thingvallavatn
and Holar aquaculture (AC) charr. The data reveal significant differences in
expression of several biological pathways during charr development. There was
also an expression difference between SB- and AC-charr in genes involved in
energy metabolism and blood coagulation genes. We confirmed differing expression
of five genes in whole embryos with qPCR, including lysozyme and natterin-like
which was previously identified as a fish-toxin of a lectin family that may be a
putative immunopeptide. We also verified differential expression of 7 genes in
the developing head that associated consistently with benthic v.s.limnetic
morphology (studied in 4 morphs). Comparison of single nucleotide polymorphism
(SNP) frequencies reveals extensive genetic differentiation between the SB and AC
charr (~1300 with more than 50% frequency difference). Curiously, three derived
alleles in the otherwise conserved 12s and 16s mitochondrial ribosomal RNA genes
are found in benthic charr. The data implicate multiple genes and molecular
pathways in divergence of small benthic charr and/or the response of aquaculture
charr to domestication. Functional, genetic and population genetic studies on
more freshwater and anadromous populations are needed to confirm the specific
loci and mutations relating to specific ecological traits in Arctic charr.
PMID- 27347372
TI - Increasing both the public health potential of basic research and the scientist
satisfaction. An international survey of bio-scientists.
AB - Basic scientific research generates knowledge that has intrinsic value which is
independent of future applications. Basic research may also lead to practical
benefits, such as a new drug or diagnostic method. Building on our previous study
of basic biomedical and biological researchers at Harvard, we present findings
from a new survey of similar scientists from three countries. The goal of this
study was to design policies to enhance both the public health potential and the
work satisfaction and test scientists' attitudes towards these factors. The
present survey asked about the scientists' motivations, goals and perspectives
along with their attitudes concerning policies designed to increase both the
practical (i.e. public health) benefits of basic research as well as their own
personal satisfaction. Close to 900 basic investigators responded to the survey;
results corroborate the main findings from the previous survey of Harvard
scientists. In addition, we find that most bioscientists disfavor present
policies that require a discussion of the public health potential of their
proposals in grants but generally favor softer policies aimed at increasing the
quality of work and the potential practical benefits of basic research. In
particular, bioscientists are generally supportive of those policies entailing
the organization of more meetings between scientists and the general public, the
organization of more academic discussion about the role of scientists in the
society, and the implementation of a "basic bibliography" for each new approved
drug.
PMID- 28694964
TI - The impact of methicillin-resistant S. aureus on length of stay, readmissions and
costs: a register based case-control study of patients hospitalized in Norway.
AB - BACKGROUND: Patients with methicillin-resistant S. aureus (MRSA) are thought to
incur additional costs for hospitals due to longer stay and contact isolation.
The aim of this study was to assess the costs associated with MRSA in Norwegian
hospitals. METHODS: Analyses were based on data fromSouth-Eastern Norway for the
year 2012 as registered in the Norwegian Surveillance System for Communicable
Diseases and the Norwegian Patient Registry. We used a matched case-control
method to compare MRSA diagnosed inpatients with non-MRSA inpatients in terms of
length of stay, readmissions within 30 days from discharge, as well as the
Diagnosis-Related Group (DRG) based costs. RESULTS: Norwegian patients with MRSA
stayed on average 8 days longer in hospital than controls, corresponding to a
ratio of mean duration of 2.08 (CI 95%, 1.75-2.47) times longer.A total of 14% of
MRSA positive inpatients were readmitted compared to 10% among controls. However,
the risk of readmission was not significantly higher for patients with MRSA. DRG
based hospital costs were 0.37 (95% CI, 0.19-0.54) times higher among cases than
controls, with a mean cost of EUR13,233(SD 26,899) and EUR7198(SD 18,159)
respectively. CONCLUSION: The results of this study indicate that Norwegian
patients with MRSA have longer hospital stays, and higher costs than those
without MRSA.
PMID- 28694965
TI - Urinary peptide-based classifier CKD273: towards clinical application in chronic
kidney disease.
AB - Capillary electrophoresis coupled with mass spectrometry (CE-MS) has been used as
a platform for discovery and validation of urinary peptides associated with
chronic kidney disease (CKD). CKD affects ~ 10% of the population, with high
associated costs for treatments. A urinary proteome-based classifier (CKD273) has
been discovered and validated in cross-sectional and longitudinal studies to
assess and predict the progression of CKD. It has been implemented in studies
employing cohorts of > 1000 patients. CKD273 is commercially available as an in
vitro diagnostic test for early detection of CKD and is currently being used for
patient stratification in a multicentre randomized clinical trial (PRIORITY). The
validity of the CKD273 classifier has recently been evaluated applying the Oxford
Evidence-Based Medicine and Southampton Oxford Retrieval Team guidelines and a
letter of support for CKD273 was issued by the US Food and Drug Administration.
In this article we review the current evidence published on CKD273 and the
challenges associated with implementation. Definition of a possible surrogate
early endpoint combined with CKD273 as a biomarker for patient stratification
currently appears as the most promising strategy to enable the development of
effective drugs to be used at an early time point when intervention can still be
effective.
PMID- 28694966
TI - Magnitude and predictors of undernutrition among children aged six to fifty nine
months in Ethiopia: a cross sectional study.
AB - BACKGROUND: Undernutrition among children continues to be a major public health
problem in developing countries. In Ethiopian, 44% of under-five children were
stunted while 29% and 10% were underweight and wasted respectively. However,
predictors of undernutrition among children were not clearly known in the study
area. Therefore, this study was aimed at determining prevalence and predictors of
undernutrition among children aged 6-59 months in Hawassa town. METHOD: A
community based cross-sectional study was conducted among 811 randomly selected
children paired with their mothers/caregivers. Mothers/caregivers were
interviewed to obtain social-demographic data and feeding practice.
Anthropometric measurement was conducted to obtain anthropometric data. Data were
entered into EPI info 6.04 and exported to SPSS 16 for analysis. Bivariate
logistic regression analysis with Crude Odds Ratio at 95%CI was used to assess
presence of association among variables. Multivariate logistic regression
analysis with Adjusted Odds Ratio at 95%CI was conducted to determine predictors
of undernutrition and association was declared significant at p <= 0.05. RESULT:
The result of our study indicated that 39.3%, 15.8% and 6.3% of children were
stunted, underweighted and wasted respectively. Multivariate logistic regression
analysis identified male sex, mother older than 35 years, not fed on colostrum,
cessation of breastfeeding before two years of age, frequency of complementary
feeding per day and diarrheal morbidity in the last 12 months were statistically
associated with stunting. Maternal education, family sizes and diarrheal
morbidity in the past 12 months were significantly associated with underweight.
Similarly, frequency of complementary feeding per day, age at cessation of
breastfeeding, preceding birth interval and not fed on colostrum were associated
to wasting. CONCLUSION: The prevalence of undernutrition; stunting, underweight
and wasting, among under-five children is very common in the study area.
Inappropriate feeding practice and diarrheal morbidity were found to be the main
risk factors for undernutrition. Appropriate factor specific interventions
including counseling on optimal child feeding practice and diarrhea prevention
should be strengthened in the study area.
PMID- 28694967
TI - The effects on anxiety and quality of life of breast cancer patients following
completion of the first cycle of chemotherapy.
AB - OBJECTIVES: Breast cancer patients as part of their treatment need to undergo
various forms of chemotherapy. This is considered as a burdensome experience for
many patients often leading to significant levels of anxiety. The aim of the
study was to explore the anxiety levels and any correlations to the quality of
life of women with breast cancer that were undergoing chemotherapy. METHODS: This
was a cross-sectional study utilizing an explanatory sequential design. Data were
collected from 355 women with breast cancer with the Self Anxiety Scale, the
EORTC QLQ-C30, the EORTC QLQ-BR23 and sociodemographic questionnaires. Further
insight to patients' experiences was given through 12 in-depth interviews.
RESULTS: Anxiety scores ranged between 24 and 75 (45.7 +/- 10.11), with 44%
reporting serious or/and intense anxiety. The results revealed statistically
significant differences on patients' anxiety levels depending on their source of
support. Overall, patients' global health-related quality of life was found to be
low to average 55.91 +/- 17.94. The results showed low emotional functioning
(49.30 +/- 29.12), low role functions (56.34 +/- 27.50) and low sexual
functioning (24.93 +/- 20.75). Patients also reported experiencing problems with
fatigue (49.04 +/- 29.12), insomnia (44.32 +/- 32.97), hair loss (48.25 +/-
38.32) and arm symptoms (36.53 +/- 23.71). Patients being solely supported by the
family experienced higher anxiety levels (p < 0.001) and lower quality of life (p
< 0.001). There was a statistically significant negative correlation between
anxiety and quality of life (r = -0.623, p < 0.001). Statistically significant
differences were also found in relation to demographics, anxiety and quality of
life. The interviews provided further evidence on the impact of anxiety on
patients' lives. CONCLUSION: The time following the completion of the first cycle
of chemotherapy is associated with anxiety and lower quality of life levels in
breast cancer patients. Healthcare providers should consider the supportive
healthcare needs from the beginning of chemotherapy in patients to optimize their
conventional and supportive healthcare outcomes.
PMID- 28694968
TI - Retropharyngeal lipoma causing obstructive sleep apnoea.
AB - We present the case of a middle-aged man whose obstructive sleep apnoea (OSA) was
caused by a retropharyngeal lipoma, with complete resolution after transoral
excision. Lipomas causing OSA are rare, and this represents the seventh reported
case in the literature.
PMID- 28694969
TI - Hypogonadotropic hypogonadism in men with hereditary hemochromatosis.
AB - Hereditary hemochromatosis is a genetic disease that progresses silently. This
disease is often diagnosed late when complications appear. Hypogonadotropic
hypogonadism (HH) is one of the classical complications of hemochromatosis. Its
frequency is declining probably because of earlier diagnosis and better informed
physicians. Certain symptoms linked to HH can have an impact on a patient's
sexuality, such as decreased libido, erectile dysfunction, and impairment of
ejaculation, as well as on his reproductive capacities. This review is based on
an online search in English, French and German language publications found in
PubMed/Medline, up to 23 September 2016 using the following key word: Male
infertility, Hypogonadotropic Hypogonadism, Hereditary Hemochromatosis. Thirty
four papers met these inclusion criteria. This review describes the impact of
iron overload on male fertility, resulting in hypogonadotropic hypogonadism and
proposes treatment modalities.
PMID- 28694970
TI - Increasing evidence indicates low bioaccumulation of carbon nanotubes.
AB - As the production of carbon nanotubes (CNTs) expands, so might the potential for
release into the environment. The possibility of bioaccumulation and
toxicological effects has prompted research on their fate and potential
ecological effects. For many organic chemicals, bioaccumulation properties are
associated with lipid-water partitioning properties. However, predictions based
on phase partitioning provide a poor fit for nanomaterials. In the absence of
data on the bioaccumulation and other properties of CNTs, the Office of Pollution
Prevention and Toxics (OPPT) within the US Environmental Protection Agency (EPA)
subjects new pre-manufacture submissions for all nanomaterials to a higher-level
review. We review the literature on CNT bioaccumulation by plants, invertebrates
and non-mammalian vertebrates, summarizing 40 studies to improve the assessment
of the potential for bioaccumulation. Because the properties and environmental
fate of CNTs may be affected by type (single versus multiwall),
functionalization, and dosing technique, the bioaccumulation studies were
reviewed with respect to these factors. Absorption into tissues and elimination
behaviors across species were also investigated. All of the invertebrate and non
mammalian vertebrate studies showed little to no absorption of the material from
the gut tract to other tissues. These findings combined with the lack of
biomagnification in the CNT trophic transfer studies conducted to date suggest
that the overall risk of trophic transfer is low. Based on the available data, in
particular the low levels of absorption of CNTs across epithelial surfaces, CNTs
generally appear to form a class that should be designated as a low concern for
bioaccumulation.
PMID- 28694971
TI - Primary intimal sarcoma of the left atrium presenting with constitutional
symptoms.
AB - Intimal (spindle-cell) sarcomas are exceptionally rare and are highly aggressive
cardiac tumors. The authors describe a case of a 43-year-old female, presenting
with a 3-month history of constitutional symptoms with fever, night sweats,
anorexia and weight loss, associated with productive cough and pleural effusion
that was admitted with clinical suspicion of pulmonary tuberculosis. The patient
developed sudden acute heart failure symptoms during hospitalization, leading to
mechanical ventilation. Computed tomography scan with contrast showed a cardiac
tumor filling the left atrium causing compression of pulmonary veins. Surgical
resection was performed and histologic examination revealed an intimal sarcoma.
Although commenced on adjuvant chemotherapy, local tumor recurrence occurred with
pericardium invasion. The patient died within 4 months of initial diagnosis. This
report aims to describe an unusual presentation of this rare disease entity, and
to discuss its highly aggressive clinical course.
PMID- 28694972
TI - Rhabdomyolysis as a rare paraneoplastic presentation of acute myeloid leukemia.
AB - We present the case of a 56-year-old man who presented with rhabdomyolysis and
was found to have acute myeloid leukemia (AML). Our case is the first to show an
association of rhabdomyolysis with AML. Although rhabdomyolysis is likely a very
rare clinical presentation of AML, our case raises awareness for workup for AML
in patients who present with rhabdomyolysis and other suspicious findings. Both
conditions are medical emergencies and require immediate treatment.
PMID- 28694973
TI - Rapid progression of solitary fibrous tumor after induction of hemodialysis.
AB - A 42-year-old male patient presented in 2002 with a solitary fibrous tumor (SFT)
arising from the visceral pleura of the right lung. Thoracic surgery was
performed to remove the tumor. A second operation to remove a recurrent tumor on
the parietal pleura of the right thorax was performed in 2010. A follow-up
computed tomography (CT) scan revealed local recurrence in the chest wall. And
then a third operation involving en bloc resection of chest wall was performed in
2012. Thereafter, a CT scan in 2015 revealed slow-growing local recurrence. In
2016, he was started on hemodialysis. Two months later he was hospitalized
because of chest pain and dyspnea. Imaging showed bilateral massive pleural
effusion and dissemination along with left pulmonary metastasis. We report a case
of SFT recurrence, which rapidly worsened after induction of hemodialysis.
Induction of hemodialysis is potentially challenging that may lead to be in a
tumor-bearing condition.
PMID- 28694974
TI - Long-term irreversible trastuzumab-induced cardiotoxicity for metastatic breast
cancer in a patient without cardiac risk factors.
AB - Trastuzumab improves clinical outcomes in patients with human epidermal growth
factor receptor-2-positive breast cancer. However, cardiotoxicity is a
potentially important concern, and the long-term cardiac effects of trastuzumab
therapy remain unclear. Although reduction of cardiac function by trastuzumab is
mostly reversible, some patients, especially those with cardiac risk factors, may
rarely experience chronic heart failure or prolonged left ventricular ejection
fraction reduction. There have been no detailed published analyses of patients
with such unfavorable clinical courses. We report the rare case of a metastatic
breast cancer in a woman without cardiac risk factors who experienced long-term
irreversible cardiotoxicity after discontinuation of trastuzumab therapy.
PMID- 28694975
TI - Running faster. Standing still.
PMID- 28694976
TI - Global Nursing-a literature review in the field of education and practice.
AB - AIM: To describe key findings of Global Nursing in empirical nursing studies.
DESIGN: A literature review using descriptive data synthesis of peer-reviewed
articles in the field of nursing education and practice. METHODS: This review of
Cinahl Complete, PubMed, PsycINFO and Scopus was undertaken using the search
strategy "global nursing". Independent title/abstract and full-text screening was
undertaken, identifying original articles written in English. RESULTS: A total of
472 titles and 170 abstracts were read through. Seventy-three articles were
included for full-text review. Twenty published studies of Global Nursing with
multiple research methodologies fulfilled the inclusion criteria. Findings were
described with five categories. Global Nursing Arena, Global Nursing Working
Environments, Global Nursing Workforce Management, Global Nursing Competencies
and Global Nursing Networking were shown to be crucial when Global Nursing was
addressed in the literature.
PMID- 28694977
TI - Learning to practise the Guided Self-Determination approach in type 2 diabetes in
primary care: A qualitative pilot study.
AB - AIM: To describe how diabetes nurses in primary care experience the process of
learning to practise the person-centred counselling approach Guided Self
Determination among adults with type 2 diabetes. DESIGN: A descriptive
qualitative design. METHOD: Data were collected in 2014-2015 by means of
individual interviews with four diabetes nurses at two points in time. The data
were analysed using qualitative content analysis. RESULTS: Three themes that
reflect nurses' processes in learning to use the Guided Self-Determination
approach were identified: (1) from an unfamiliar interaction to "cracking the
code"; (2) from an unspecific approach to a structured, reflective, but demanding
approach; and (3) from a nurse-centred to a patient-centred approach. The overall
findings indicate that the process of learning to practise Guided Self
Determination increased the nurses' counselling competence. Moreover, the nurses
perceived the approach to be generally helpful, as it stimulated reflections
about diabetes management and about their own counselling practices.
PMID- 28694978
TI - Asthma in adolescence affects daily life and school attendance - Two cross
sectional population-based studies 10 years apart.
AB - AIM: The aim of this study was to study the impact of asthma on daily life,
school absenteeism and physical education. In addition, to describe asthma
triggers at school. DESIGN: Two cross-sectional population-based studies ten
years apart. METHOD: Within the OLIN-studies, in 2003 (n = 3,327) and in 2013 (n
= 2,345) adolescents (14-15 years) answered an expanded ISAAC questionnaire. Of
these, 8% and 11%, respectively with current asthma participated in this study.
RESULTS: Between the years 2003-2013, the proportion of adolescents reporting
that asthma interfered with daily life had increased, in 2013, girls were
significantly more affected than boys. The proportion reporting a worsening of
asthma at school had decreased, but it was still over a quarter. The proportion
of absenteeism from school and from physical education was at the same level both
years. Asthma triggers were described to be poor air quality, poorly cleaned
environment, allergens, strong fragrance, rebuilding projects, physical education
and stress.
PMID- 28694979
TI - Barriers and carriers: a multicenter survey of nurses' barriers and facilitators
to monitoring of nurse-sensitive outcomes in intensive care units.
AB - AIM: To identify nurses' barriers and facilitators to monitoring of nurse
sensitive outcomes in intensive care units (ICUs), and to explore influential
nurse characteristics and work environment factors. DESIGN: A cross-sectional
survey in three Dutch ICUs between October 2013 - June 2014. METHODS: A
questionnaire with questions regarding facilitators and three types of barriers:
knowledge, attitude and behaviour. The Dutch Essentials of Magnetism II was used
to examine work environments. RESULTS: All 126 responding nurses identified
pressure ulcers and patient satisfaction as outcomes that are nurse-sensitive and
nurses' full responsibility. Lack of time (behaviour) was perceived as the most
prominent barrier, followed by unfamiliarity with mandatory indicators
(knowledge), and unreliability of indicators as benchmark data (attitude).
Education and clear policies were relevant facilitators. Of nurse
characteristics, only regularity of shifts was related to perceived attitude
related barriers. The work environment factor "clinical autonomy" was potentially
associated with behaviour related barriers.
PMID- 28694980
TI - A comparative correlational study of coping strategies and quality of life in
patients with chronic heart failure and the general Swedish population.
AB - AIM: The aim was to compare coping strategies and quality of life (QoL) in
patients with chronic heart failure (CHF) with such strategies and QOL in persons
from two general Swedish populations and to investigate relationships between
personal characteristics and coping strategies. DESIGN: A cross-sectional,
comparative and correlational design was used to examine data from three sources.
METHODS: The patient group (n = 124), defined using ICD-10, was selected
consecutively from two hospitals in central Sweden. The population group (n =
515) consisted of persons drawn randomly from the Swedish population. Data were
collected with questionnaires in 2011; regarding QoL, Swedish population
reference data from 1994 were used. RESULTS: Overall, women used more coping
strategies than men did. Compared with the general population data from SF-36,
patients with CHF rated lower QoL. In the regression models, perceived low
"efficiency in managing psychological aspects of daily life" increased use of
coping. Other personal characteristics related to increased use of coping
strategies were higher education, lower age and unsatisfactory economic
situation.
PMID- 28694981
TI - Family-centred care in cystic fibrosis: a pilot study in North Queensland,
Australia.
AB - AIMS: The aims were to: (i) examine perceptions of family-centred care of parents
of children with cystic fibrosis and healthcare professionals who care for them;
(ii) test design and tools in a regional population. DESIGN: Quantitative pilot
study of existing questionnaire. METHODS: The methods involved were comparative,
cross-sectional survey of parents of children with cystic fibrosis and health
staff in North Queensland, using "Perceptions of Family Centered Care - Parent"
and "Perceptions of Family Centered Care - Staff" questionnaires; and descriptive
study of tools. RESULTS: Eighteen staff, 14 parents (78%, 61%); using Mann
Whitney U, showed no significant differences in scores in categories: 'support'
'respect', 'collaboration'. Comments about suitability of questionnaires varied,
but were largely positive.
PMID- 28694982
TI - Othering in the nursing context: A concept analysis.
AB - AIM: 'Othering' is described as a social process whereby a dominant group or
person uses negative attributes to define and subordinate others. Literature
suggests othering creates exclusive relationships and puts patients at risk for
suboptimal care. A concept analysis delineating the properties of othering was
conducted to develop knowledge to support inclusionary practices in nursing.
DESIGN: Rodgers' Evolutionary Method for concept analysis guided this study.
METHODS: The following databases were searched spanning the years 1999-2015:
CINAHL, PUBMED, PsychINFO and Google. Search terms included "othering", "nurse",
"other", "exclusion" and "patient". RESULTS: Twenty-eight papers were analyzed
whereby definitions, related concepts and othering attributes were identified.
Findings support that othering in nursing is a sequential process with a
trajectory aimed at marginalization and exclusion, which in turn has a negative
impact on patient care and professional relationships. Implications are discussed
in terms of deriving practical solutions to disrupt othering. We conclude with a
conceptual foundation designed to support inclusionary strategies in nursing.
PMID- 28694983
TI - Effects of a sensory-motor orthotic on postural instability rehabilitation in
Parkinson's disease: a pilot study.
AB - BACKGROUND: Proprioceptive deficits have been largely documented in PD patients,
thus external sensory signals (peripheral sensory feedback) are often used to
compensate the abnormalities of proprioceptive integration. This pilot study aims
to evaluate the feasibility and the effectiveness of a rehabilitation-training
program, combined with the use of a sensory-motor orthotic in improving balance
in a small sample of PD patients. METHODS: Twenty PD patients were randomly
allocated into two groups: (i) the Experimental group, where participants were
asked to wear a sensory-motor orthotic during the balance training program and
(ii) the Control group, where subjects performed an identical training program
without wearing any kind of orthotics. In all, the training program lasted 10
sessions (5 days a week for 2 weeks) and the clinical and instrumental
assessments were performed at baseline, immediately after the end of the training
and 4 weeks after the rehabilitative program was stopped. RESULTS: All clinical
outcome measures tested improved significantly at post and follow-up evaluations
in both groups. Interestingly, at the end of the training, only the experimental
group obtained a significant improvement in the functional reaching test (sway
area - eyes closed) measured by means of stabilometric platform and this result
was maintained in the follow-up evaluation. CONCLUSIONS: Our preliminary results
suggested that the use of a sensory-motor orthotic, in combination with a
tailored balance training, is feasible and it seems to positively impact on
balance performance in Parkinson's disease. TRIAL REGISTRATION: EudraCT N. 003020
36 - 2013.
PMID- 28694984
TI - Behavioral and physiological changes during heat stress in Corriedale ewes
exposed to water deprivation.
AB - This study was conducted to investigate the behavioral and physiological changes
of heat stressed Corriedale ewes exposed to water deprivation. Nine Corriedale
ewes (average BW = 45 +/- 3.7 kg) were individually fed diets based on
maintenance requirements in metabolic crates. Ewes were assigned into three
groups (9 sheep per treatment) according to a 3 * 3 Latin square design for 3
periods with 21-d duration for each period. The control (CON) group was given
free access to water, 2 h water deprivation (2hWD), and 3 h water deprivation
(3hWD) following feeding. No differences were found in fecal excretion frequency,
standing frequency (number/d), and sitting frequency among the groups (p > 0.05).
Measurements of standing duration (min/d) and urine excretion frequency
(number/d) showed a significant decrease whereas sitting duration (min/d) showed
a significant increase in the 2hWD and 3hWD groups when compared with the CON
group (p < 0.05). Fecal score and heart rate (number/min) were not different
among the groups (p > 0.05). However, respiratory rate (number/min) and panting
score were found to be significantly higher in the 2hWD and 3hWD groups than in
the CON group (p < 0.05). It is concluded that water deprivation following
feeding intensifies physiological heat stress related indicators such as
respiratory rate and panting score and changes behavioral parameters such as
water intake and urine excretion frequency in heat stressed ewes. Daily
adaptation to the extreme environmental conditions may occur actively in ewes.
PMID- 28694985
TI - Emergence of Brachyspira species and strains: reinforcing the need for
surveillance.
AB - This short review discusses the increasing complexity that has developed around
the understanding of Brachyspira species that infect pigs, and their ability to
cause disease. It describes the recognition of new weakly haemolytic Brachyspira
species, and the growing appreciation that Brachyspira pilosicoli and some other
weakly haemolytic species may be pathogenic in pigs. It discusses swine dysentery
(SD) caused by the strongly haemolytic Brachyspira hyodysenteriae, particularly
the cyclical nature of the disease whereby it can largely disappear as a clinical
problem from a farm or region, and re-emerge years later. The review then
describes the recent emergence of two newly described strongly haemolytic
pathogenic species, "Brachyspira suanatina" and "Brachyspira hampsonii" both of
which appear to have reservoirs in migratory waterbirds, and which may be
transmitted to and between pigs. "B. suanatina" seems to be confined to
Scandinavia, whereas "B. hampsonii" has been reported in North America and
Europe, causes a disease indistinguishable from SD, and has required the
development of new routine diagnostic tests. Besides the emergence of new
species, strains of known Brachyspira species have emerged that vary in important
biological properties, including antimicrobial susceptibility and virulence.
Strains can be tracked locally and at the national and international levels by
identifying them using multilocus sequence typing (MLST) and comparing them
against sequence data for strains in the PubMLST databases. Using MLST in
conjunction with data on antimicrobial susceptibility can form the basis for
surveillance programs to track the movement of resistant clones. In addition some
strains of B. hyodysenteriae have low virulence potential, and some of these have
been found to lack the B. hyodysenteriae 36 kB plasmid or certain genes on the
plasmid whose activity may be associated with colonization. Lack of the plasmid
or the genes can be identified using PCR testing, and this information can be
added to the MLST and resistance data to undertake detailed surveillance. Strains
of low virulence are particularly important where they occur in high health
status breeding herds without causing obvious disease: potentially they could be
transmitted to production herds where they may colonize more effectively and
cause disease under stressful commercial conditions.
PMID- 28694986
TI - Assessment of the face validity, feasibility and utility of a patient-completed
questionnaire for polymyalgia rheumatica: a postal survey using the QQ-10
questionnaire.
AB - BACKGROUND: The development of a patient-reported outcome measure (PROM) for
polymyalgia rheumatica (PMR), a condition that causes pain, stiffness and
disability, is necessary as there is no current validated disease-specific
measure. Initial literature synthesis and qualitative research established a
conceptual framework for the condition along with a list of symptoms and effects
of PMR that patients felt were important to them. These findings were used to
derive the candidate items for a patient-completed questionnaire. We aim to
establish the face validity of this initial "long form" of a PROM. METHODS:
People with a current or previous diagnosis of PMR were recruited both from the
community and from rheumatology clinics. They were asked to complete the PMR
questionnaire along with the QQ-10 questionnaire, which is a measure used to
assess the face validity, feasibility and utility of patient healthcare
questionnaires. RESULTS: A total of 28 participants with an age range of 59-85
years and a length of time since diagnosis from 4 months to 18 years completed
the QQ-10. The overall mean "value" score was 79% (SD 12), and the mean "burden"
score was 21% (SD 18). The free-text comments were analysed thematically and were
found to focus on layout, content, where in the clinical pathway the
questionnaire would be most beneficial, specific items missing and other areas
for consideration. CONCLUSIONS: The high mean value score and low burden score
indicate that the questionnaire has good face validity and is acceptable to
patients. The questionnaire now needs to undergo further psychometric evaluation
and refinement to develop the final tool for use in clinical practice and
research.
PMID- 28694987
TI - The EXPRESS Study: Exercise and Protein Effectiveness Supplementation Study
supporting autonomy in community dwelling frail older people-study protocol for a
randomized controlled pilot and feasibility study.
AB - BACKGROUND: Research has repeatedly demonstrated that exercise has a positive
impact on physical function and is beneficial in the treatment of physical
frailty. However, an even more effective strategy for managing physical frailty
might be the combination of multicomponent exercise with the intake of high
quality protein supplements, but the efficacy remains unclear for older adults
who are already pre-frail and frail. The aim is to examine the feasibility of
recruiting frail older adults to participate in a trial designed to determine the
potential effects of a 6-month exercise and nutrition intervention on physical
function. The feasibility objectives will include frail older peoples'
compliance, the safety and tolerability of the trial, the estimation of estimates
to aid sample size calculation, and the potential efficacy. Primary outcomes for
the main trial will include gait speed, grip strength and physical performance.
Secondary outcomes will include frailty status, muscle mass, nutritional intake,
physical activity levels, cognitive performance and quality of life.
METHODS/DESIGN: A randomised, parallel, control pilot and feasibility study will
be conducted. All participants will be randomly assigned to either (a) an
exercise program + high-quality protein supplement or (b) an exercise program +
low-quality protein supplement. Both protein supplements will be matched closely
in colour, flavour and packaging so that both the participants and the research
staff are blinded. The exercise program will be the same in both groups.
Assessments will be conducted at baseline and at 3 and 6 months and include gait
speed, grip strength, the Short Physical Performance Battery, Timed Up and Go
Test, FRAIL Screen, bioelectrical impedance analyses, 24-h dietary recall, Katz
Activities of Daily Living, Lawton Instrumental Activities of Daily Living, the
Trail Making Test, Short Form Health Survey-36, and 1 week accelerometer
quantification. The data will be analysed using an ANCOVA model. DISCUSSION: This
study is expected to provide much needed insight into the feasibility of
recruiting and retaining frail older adults into community-based intervention
programs, while providing knowledge relating to the safety, tolerability and
benefits of a combined exercise and protein supplement program designed to halt
or reverse the transition of physical frailty in the community. If shown to be
effective, this strategy could be included in the best practice clinical
guidelines for community-dwelling older adults who are pre-frail or frail. TRIAL
REGISTRATION: Australian New Zealand Clinical Trials Registry,
ACTRN12616000521426.
PMID- 28694988
TI - Enhancing Knowledge and InterProfessional care for Heart Failure (EKWIP-HF) in
long-term care: a pilot study.
AB - BACKGROUND: Heart failure (HF) affects 20% of long-term care (LTC) residents and
is associated with significant morbidity, acute care visits, and mortality.
Barriers to HF management are staff knowledge gaps and ineffective
interprofessional (IP) communication. This pilot study assessed the
acceptability, feasibility, and impact of an intervention to (1) improve HF
knowledge; (2) improve IP communication; and (3) integrate improved knowledge and
communication processes into work routines. METHODS: The intervention provides
multimodal IP education about HF in LTC, including specialist-supported bedside
teaching. It was piloted on single units in two facilities. A mixed-methods
repeated-measures approach was used to collect qualitative and quantitative
process and outcome data at baseline and 6 months post-intervention. RESULTS:
Results were similar at both sites. Participants developed optimized IP
communication to promote HF care. Results indicate a perceived increase in staff
confidence and self-efficacy, strengthened assessment and clinical proficiency
skills, and more effective IP collaboration. Staff deemed the intervention useful
and feasible. CONCLUSIONS: This pilot study suggests that a novel intervention in
which HF-specific knowledge is applied by LTC staff to improve IP collaboration
in their own work place is acceptable and feasible and has a favourable
preliminary impact on staff knowledge and IP communication.
PMID- 28694989
TI - Manual acupuncture plus usual care versus usual care alone in the treatment of
endometriosis-related chronic pelvic pain: study protocol for a randomised
controlled feasibility study.
AB - BACKGROUND: Endometriosis is the most common cause of chronic pelvic pain
worldwide. Non-surgical treatments are effective for only 30-50% of women and
have a significant side effect burden that leads to high discontinuation rates.
Surgery can be effective but is expensive and invasive, and symptoms tend to
recur within 5 years. There is early evidence that acupuncture may be effective
in treating endometriosis-related chronic pelvic pain, showing clinically
significant analgesia. Both levels of inflammation and pain processing have been
shown to be altered in women with chronic pelvic pain. Acupuncture has been shown
to reduce inflammation and change central pain processing in other conditions,
but research on women with endometriosis is currently lacking. The aim of this
feasibility study is to provide data on recruitment rates, retention,
appropriateness of outcome measures, minimal clinically important difference in
numeric rated scales for pain and the potential effect of acupuncture on pain
processing and markers of inflammation in endometriosis-related CPP. METHODS: We
will include women aged 18-45 years with a diagnosis of endometriosis via
laparoscopy in the past 5 years. A total of 30 participants will be recruited and
randomly allocated in a 1:1 ratio to receive acupuncture or usual care. Women in
the acupuncture group will receive two 45-min treatment sessions per week for 8
weeks (total of 16 sessions). Women in the usual care group will continue with
their current treatment regimen. The primary feasibility outcomes are recruitment
rates, retention rates and the safety and acceptability of the intervention;
secondary patient-centred outcomes include a change in 0-10 daily pelvic pain
ratings, the Endometriosis Health Profile 30 (EHP-30) and changes in conditioned
pain modulation, resting and task-related EEG activity and inflammatory markers.
Analyses will be performed blind to group allocation. DISCUSSION: This is a two
armed, assessor blind, randomised controlled feasibility trial. Data will be
compared at baseline and trial completion 8 weeks later. Outcomes from this
feasibility study will inform a larger, fully powered clinical trial should the
treatment show trends for potential effectiveness. TRIAL REGISTRATION: Australian
New Zealand Clinical Trials Registry, ACTRN12617000053325
(http://www.ANZCTR.org.au/ACTRN12617000053325.aspx).
PMID- 28694990
TI - Feasibility of a randomized single-blind crossover trial to assess the effects of
the second-generation slow-release dopamine agonists pramipexole and ropinirole
on cued recall memory in idiopathic mild or moderate Parkinson's disease without
cognitive impairment.
AB - BACKGROUND: The aim was to assess the feasibility of a single-centre, single
blind, randomized, crossover design to explore the effects of two slow-release
dopamine agonists, ropinirole and pramipexole, on cued recall in Parkinson's
disease. As the design required a switch from the prescribed agonist (pramipexole
to-ropinirole, or ropinirole-to-pramipexole), the primary objectives were to (a)
examine the efficacy of processes and procedures used to manage symptoms during
the washout period and (b) to use cued recall estimates to inform a power
calculation for a definitive trial. Secondary objectives were to assess consent
and missing data rates, acceptability of clinical support for the OFF sessions,
experience of the OFF sessions and of agonist switching, barriers-to
participation for patients and informal caregivers. METHODS: Patients were
randomized in a 1:1 ratio to two treatment arms and stabilized on each agonist
for 6 weeks. The arms differed only in the sequence in which the agonists were
administered. Cued recall was assessed ON medication and, following a washout
period resulting in 93.75% agonist elimination, OFF medication. RESULTS: A total
of 220 patients were screened: 145 were excluded and 75 invitations to
participate were sent to eligible patients. Fifty-three patients declined, 22
consented and 16 completed the study. There were no serious adverse events, and
rates of non-serious adverse events were equivalent between the agonists. Using
the largest standard deviation (SD) of the ON-OFF difference cued recall score
(inflated by ~25% to give a conservative estimate of the SD in a definitive
trial) and assuming an effect of at least 10% of the observed range of OFF
medication cued recall scores for either agonist to be clinically important, a
main trial requires a sample size of just under 150 patients. The consent and
missing data rates were 29 and 27% respectively. The washout period and the
preparation for the OFF sessions were acceptable, and the sessions were
manageable. The experience of switching was also manageable. Barriers to
participation included concerns about disease stability, side effects, research
process, carer workload and accessibility of the information sheet. CONCLUSIONS:
This study presented challenges to recruitment both in design and execution, and
while it was a major aim of the study to assess this, evaluation of these
challenges provided the opportunity to explore how they could be overcome for
future studies. TRIAL REGISTRATION: EudraCT 2012-000801-64.
PMID- 28694991
TI - A study protocol of a three-group randomized feasibility trial of an online yoga
intervention for mothers after stillbirth (The Mindful Health Study).
AB - BACKGROUND: In the USA, stillbirth (in utero fetal death >=20 weeks gestation) is
a major public health issue. Women who experience stillbirth, compared to women
with live birth, have a nearly sevenfold increased risk of a positive screen for
post-traumatic stress disorder (PTSD) and a fourfold increased risk of depressive
symptoms. Because the majority of women who have experienced the death of their
baby become pregnant within 12-18 months and the lack of intervention studies
conducted within this population, novel approaches targeting physical and mental
health, specific to the needs of this population, are critical. Evidence suggests
that yoga is efficacious, safe, acceptable, and cost-effective for improving
mental health in a variety of populations, including pregnant and postpartum
women. To date, there are no known studies examining online-streaming yoga as a
strategy to help mothers cope with PTSD symptoms after stillbirth. METHODS: The
present study is a two-phase randomized controlled trial. Phase 1 will involve
(1) an iterative design process to develop the online yoga prescription for phase
2 and (2) qualitative interviews to identify cultural barriers to recruitment in
non-Caucasian women (i.e., predominately Hispanic and/or African American) who
have experienced stillbirth (N = 5). Phase 2 is a three-group randomized
feasibility trial with assessments at baseline, and at 12 and 20 weeks post
intervention. Ninety women who have experienced a stillbirth within 6 weeks to 24
months will be randomized into one of the following three arms for 12 weeks: (1)
intervention low dose (LD) = 60 min/week online-streaming yoga (n = 30), (2)
intervention moderate dose (MD) = 150 min/week online-streaming yoga (n = 30), or
(3) stretch and tone control (STC) group = 60 min/week of stretching/toning
exercises (n = 30). DISCUSSION: This study will explore the feasibility and
acceptability of a 12-week, home-based, online-streamed yoga intervention, with
varying doses among mothers after a stillbirth. If feasible, the findings from
this study will inform a full-scale trial to determine the effectiveness of home
based online-streamed yoga to improve PTSD. Long-term, health care providers
could use online yoga as a non-pharmaceutical, inexpensive resource for
stillbirth aftercare. TRIAL REGISTRATION: NCT02925481.
PMID- 28694992
TI - A mixed methods study to evaluate the feasibility of using the Adolescent
Diabetes Needs Assessment Tool App in paediatric diabetes care in preparation for
a longitudinal cohort study.
AB - BACKGROUND: An evaluation study was carried out to determine the feasibility of
integrating the Adolescent Diabetes Needs Assessment Tool (ADNAT) App into UK
paediatric diabetes care, to ascertain best practice standards and to determine
methodological recommendations for a future cohort study. METHODS: A non
randomised, cohort, mixed methods study design was used to ensure equality of
access to ADNAT for all participants at three sites in the North West of England.
Following UK Medical Research Council guidance, the RE-AIM (reach, effectiveness
(potential and perceived), adoption, implementation, maintenance) framework was
used to guide study objectives and feasibility outcomes. Patients who completed
ADNAT (completers) were compared with those who failed to complete (non
completers). Patients' glycaemic control (HbA1c) was accessed from their clinical
data at baseline and at 6 months, alongside their ADNAT scores which were
correlated with changes in HbA1c levels. The diabetes teams (respondents)
completed a web-based survey and attended focus group interviews. RESULTS: Eighty
nine patients were recruited. Withdrawal rates were low at 4.5% (n = 4). Forty
four patients (49.4%) completed ADNAT, leaving 45 (50.6%) non-completers. There
were large baseline differences in HbA1c and variable rates of change at 6
months. After adjusting for baseline HbA1C and site in an analysis of covariance,
completers had a lower post-ADNAT mean HbA1C level than non-completers at 6
months (-5.42 mmol/mol, 95% CI -11.48, 0.64). Patients' glycaemic control (HbA1c)
at 6 months correlated reasonably well with their ADNAT scores (Spearman's rho =
0.46). Survey and focus group data showed that ADNAT was judged to be an
effective clinical tool by the diabetes teams. Value to patients was perceived by
the teams to be linked to parental support, age and previous diabetes education.
The combined data triangulated. It served to capture different dimensions which
were used to define changes to achieve practice standards and methodological
recommendations. CONCLUSIONS: The combined data showed that ADNAT has the
potential to be a clinically viable tool. It has demonstrated the need for a
randomised design that is tailored for a 'hard to reach' adolescent population. A
cluster randomised controlled trial that involves sequential but random rollout
of ADNAT over multiple time periods may be the most appropriate and is currently
being considered for the larger study. TRIAL REGISTRATION: NIHR Children's
Clinical Research Network, UKCRN ID 6633.
PMID- 28694993
TI - Improving the efficiency of trials using innovative pilot designs: the next phase
in the conduct and reporting of pilot and feasibility studies.
AB - With continuously increasing costs of conducting trials, use of innovative
approaches-such as pragmatic trials, registry-based randomised trials, adaptive
trials, personalised medicine trials, platform trials, and basket trials-to the
design and conduct of clinical trials has been advocated as one of the most
promising solutions. In this editorial, we propose that the next wave of
feasibility or pilot studies should focus on assessing the feasibility of trials
using these designs, which we see as an imperative in order to unleash their
potential to reduce trial costs and accelerate the drug development process and
the search for best treatments, so that the right treatments can be delivered as
soon as possible to the right patients.
PMID- 28694994
TI - Pilot randomised controlled trial of the ENGAGER collaborative care intervention
for prisoners with common mental health problems, near to and after release.
AB - BACKGROUND: Rates of common mental health problems are much higher in prison
populations, but access to primary care mental health support falls short of
community equivalence. Discontinuity of care on release is the norm and is
further complicated by substance use and a range of social problems, e.g.
homelessness. To address these problems, we worked with criminal justice, third
sector social inclusion services, health services and people with lived
experiences (peer researchers), to develop a complex collaborative care
intervention aimed at supporting men with common mental health problems near to
and following release from prison. This paper describes an external pilot trial
to test the feasibility of a full randomised controlled trial. METHODS: Eligible
individuals with 4 to 16 weeks left to serve were screened to assess for common
mental health problems. Participants were then randomised at a ratio of 2:1
allocation to ENGAGER plus standard care (intervention) or standard care alone
(treatment as usual). Participants were followed up at 1 and 3 months' post
release. Success criteria for this pilot trial were to meet the recruitment
target sample size of 60 participants, to follow up at least 50% of participants
at 3 months' post release from prison, and to deliver the ENGAGER intervention.
Estimates of recruitment and retention rates and 95% confidence intervals (CIs)
are reported. Descriptive analyses included summaries (percentages or means) for
participant demographics, and baseline characteristics are reported. RESULTS:
Recruitment target was met with 60 participants randomised in 9 months. The
average retention rates were 73% at 1 month [95% CI 61 to 83] and 47% at 3 months
follow-up [95% CI 35 to 59]. Ninety percent of participants allocated to the
intervention successfully engaged with a practitioner before release and 70%
engaged following release. CONCLUSIONS: This pilot confirms the feasibility of
conducting a randomised trial for prison leavers with common mental health
problems. Based on this pilot study and some minor changes to the trial design
and intervention, a full two-centre randomised trial assessing the clinical and
cost-effectiveness of the ENGAGER intervention is currently underway.
PMID- 28694995
TI - A pilot randomised clinical trial of physiotherapy (manual therapy, exercise, and
education) for early-onset hip osteoarthritis post-hip arthroscopy.
AB - BACKGROUND: Despite the increasing use of hip arthroscopy for hip pain, there is
no level 1 evidence to support physiotherapy rehabilitation programs following
this procedure. The aims of this study were to determine (i) what is the
feasibility of a randomised controlled trial (RCT) investigating a targeted
physiotherapy intervention for early-onset hip osteoarthritis (OA) post-hip
arthroscopy? and (ii) what are the within-group treatment effects of the
physiotherapy intervention and a health-education control group? METHODS: This
study was a pilot single-blind RCT conducted in a private physiotherapy clinic in
Hobart, Australia. Patients included 17 volunteers (nine women; age 32 +/- 8
years; body mass index = 25.6 +/- 5.1 kg/m2) who were recruited 4-14 months post
hip arthroscopy, with chondropathy and/or labral pathology at the time of
surgery. Interventions included a physiotherapy treatment program that was semi
standardised and consisted of (i) manual therapy; (ii) hip strengthening and
functional retraining; and (iii) health education. Control treatment encompassed
individualised health education sessions. The primary outcome measure was
feasibility, which was reported as percentage of eligible participants enrolled,
adherence with the intervention, and losses to follow-up. The research process
was evaluated using interviews, and an estimated sample size for a definitive
study is offered. Secondary outcomes included the Hip disability and
Osteoarthritis Outcome Score (HOOS) and the International Hip Outcome Tool (IHOT
33) patient-reported outcomes. RESULTS: Seventeen out of 48 eligible patients
(35%) were randomised. Adherence to the intervention was 100%, with no losses to
follow-up. The estimated sample size for a full-scale RCT was 142 patients. The
within-group (95% confidence intervals) change scores for the physiotherapy group
were HOOS-Symptoms 6 points (-4 to 16); HOOS-Pain 10 points (-2 to 22); HOOS
Activity of Daily Living 8 points (0 to 16); HOOS-Sport 3 points (-12 to 19);
HOOS-Quality of Life 3 points (-7 to 13); and IHOT-33 7 points (-10 to 25). The
within-group (95% confidence intervals) change scores for the control group were
HOOS-Symptoms -4 points (-17 to 9); HOOS-Pain -2 points (-18 to 13); HOOS
Activity of Daily Living -7 points (-17 to 4); HOOS-Sport 4 points (-16 to 23);
HOOS-Quality of Life -5 points (-18 to 9); and IHOT-33 -4 points (-27 to 19).
Suggestions to improve study design included greater supervision of exercises and
increased access to physiotherapy appointments. CONCLUSIONS: Results support the
feasibility of a full-scale RCT, and recommendations for an adequately powered
and improved study to determine the efficacy of this physiotherapy intervention
post-hip arthroscopy to reduce pain and improve function are provided. TRIAL
REGISTRATION: Australian Clinical Trials Registry, ACTRN12614000426684.
PMID- 28694996
TI - An efficient system for homology-dependent targeted gene integration in medaka
(Oryzias latipes).
AB - BACKGROUND: The CRISPR/Cas system is a powerful genome editing tool that enables
targeted genome modifications in various organisms. In medaka (Oryzias latipes),
targeted mutagenesis with small insertions and deletions using this system have
become a robust technique and are now widely used. However, to date there have
been only a small number of reports on targeted gene integration using this
system. We thus sought in the present study to identify factors that enhance the
efficiency of targeted gene integration events in medaka. RESULTS: We show that
longer homology arms (ca. 500 bp) and linearization of circular donor plasmids by
cleavage with bait sequences enhances the efficiency of targeted integration of
plasmids in embryos. A new bait sequence, BaitD, which we designed and selected
by in silico screening, achieved the highest efficiency of the targeted gene
integration in vivo. Using this system, donor plasmids integrated precisely at
target sites and were efficiently transmitted to progeny. We also report that the
genotype of F2 siblings, obtained by mating of individuals harboring two
different colors of fluorescent protein genes (e.g. GFP and RFP) in the same
locus, can be easily and rapidly determined non-invasively by visual observations
alone. CONCLUSION: We report that the efficiency of targeted gene integration can
be enhanced by using donor vectors with longer homologous arms and linearization
using a highly active bait system in medaka. These findings may contribute to the
establishment of more efficient systems for targeted gene integration in medaka
and other fish species.
PMID- 28694997
TI - Antiviral drug resistance as an adaptive process.
AB - Antiviral drug resistance is a matter of great clinical importance that,
historically, has been investigated mostly from a virological perspective.
Although the proximate mechanisms of resistance can be readily uncovered using
these methods, larger evolutionary trends often remain elusive. Recent interest
by population geneticists in studies of antiviral resistance has spurred new
metrics for evaluating mutation and recombination rates, demographic histories of
transmission and compartmentalization, and selective forces incurred during viral
adaptation to antiviral drug treatment. We present up-to-date summaries on
antiviral resistance for a range of drugs and viral types, and review recent
advances for studying their evolutionary histories. We conclude that information
imparted by demographic and selective histories, as revealed through population
genomic inference, is integral to assessing the evolution of antiviral resistance
as it pertains to human health.
PMID- 28694999
TI - Fusion of a superfamily 1 helicase and an inactivated DNA polymerase is a
signature of common evolutionary history of Polintons, polinton-like viruses,
Tlr1 transposons and transpovirons.
AB - Polintons (polintoviruses), polinton-like viruses (PLVs) and virophages belong to
a recently described major class of eukaryotic viruses that is characterized by a
distinct virion morphogenetic protein module and, in many members, a protein
primed family B DNA polymerase (pDNAP). All Polintons, by definition, encode a
pDNAP and a retrovirus-like integrase. Most of the PLV lack these genes and
instead encode a large protein containing a superfamily 1 (SF1) helicase domain.
We show here that the SF1 helicase domain-containing proteins of the PLV also
contain an inactivated pDNAP domain. This unique helicase-pDNAP fusion is also
encoded by transpovirons, enigmatic plasmid-like genetic elements that are
associated with giant viruses of the family Mimiviridae. These findings indicate
the directionality of evolution of different groups of viruses and mobile
elements in the Polinton-centered class. We propose that the PLV evolved from a
polinton via fusion of the pDNAP gene with a helicase gene that was accompanied
by mutations in the pDNAP active site, likely resulting in inactivation of the
polymerase activity. The transpovirons could have evolved from PLV via the loss
of several genes including those encoding the morphogenetic module proteins.
These findings reaffirm the central evolutionary position of the Polintons in the
evolution of eukaryotic viruses and other mobile genetic elements.
PMID- 28694998
TI - Rapid outbreak sequencing of Ebola virus in Sierra Leone identifies transmission
chains linked to sporadic cases.
AB - To end the largest known outbreak of Ebola virus disease (EVD) in West Africa and
to prevent new transmissions, rapid epidemiological tracing of cases and contacts
was required. The ability to quickly identify unknown sources and chains of
transmission is key to ending the EVD epidemic and of even greater importance in
the context of recent reports of Ebola virus (EBOV) persistence in survivors.
Phylogenetic analysis of complete EBOV genomes can provide important information
on the source of any new infection. A local deep sequencing facility was
established at the Mateneh Ebola Treatment Centre in central Sierra Leone. The
facility included all wetlab and computational resources to rapidly process EBOV
diagnostic samples into full genome sequences. We produced 554 EBOV genomes from
EVD cases across Sierra Leone. These genomes provided a detailed description of
EBOV evolution and facilitated phylogenetic tracking of new EVD cases.
Importantly, we show that linked genomic and epidemiological data can not only
support contact tracing but also identify unconventional transmission chains
involving body fluids, including semen. Rapid EBOV genome sequencing, when linked
to epidemiological information and a comprehensive database of virus sequences
across the outbreak, provided a powerful tool for public health epidemic control
efforts.
PMID- 28695000
TI - Ocular Image and Haemodynamic Features Associated with Different Gradings of
Ipsilateral Internal Carotid Artery Stenosis.
AB - OBJECTIVES: To analyse the changes of ocular haemodynamics and morphology in
Chinese patients with internal carotid artery (ICA) stenosis in the current
study. METHODS: A retrospective case-control study was conducted with 219
patients. The haemodynamic characteristics, the calibre of retinal vessels, and
the subfoveal choroidal thickness (SFChT) were compared. We analysed the
correlations with the degree of ipsilateral ICA stenosis. RESULTS: There were no
significant differences among the groups in the central retinal artery equivalent
(CRAE), central retinal vein equivalent (CRVE), and AVR (p = 0.073, p = 0.188,
and p = 0.738, resp.). The peak systolic velocity (PSV) and end diastolic
velocity (EDV) in the central retinal artery (CRA) and the posterior ciliary
artery (PCA) were significantly lower than normal eyes (p < 0.001). The outer
retinal layer thickness and SFChT values of the ICA stenosis groups were
significantly lower than normal eyes (p = 0.030 and p < 0.001, resp.).
CONCLUSION: The PSV and EDV in CRA and PCA and the SFChT and outer retinal layer
thickness of ICA eyes were significantly lower than normal eyes. ICA stenosis may
impact choroidal haemodynamics, and decreased choroidal circulation might affect
the discordance of the SFChT and the outer retinal layer thickness.
PMID- 28695001
TI - Novel Genetic Findings in a Chinese Family with Axenfeld-Rieger Syndrome.
AB - PURPOSE: To describe a Chinese family with Axenfeld-Rieger syndrome (ARS) and
report our novel genetic findings. METHODS: Nine members of the same family
underwent complete ophthalmologic examinations and genetic analysis. Genomic DNA
was isolated from veinal blood and amplifed using PCR; the products of PCR were
sequenced and compared with FOXC1 and PITX2 genes, from which the mutations were
found. RESULTS: Through the ophthalmologic examinations, 8 subjects were
diagnosed as ARS and 1 subject was normal. A homozygous mutation
c.1139_1141dupGCG(p.Gly380_Ala381insGly) and a heterozygous mutation
c.1359_1361dupCGG(p.Gly456_Gln457insGly) in FOXC1 were identified in all
subjects. The mutation (c.-10-30T>C) was identified in PITX2 in subjects III-1
and III-3. CONCLUSIONS: We found novel gene mutations in a Chinese family with
ARS, which provides us with a better understanding of the gene mutation spectrum
of ARS and the assistance for the genetic counseling and gene-specific therapy in
the future.
PMID- 28695002
TI - Effect of Topically Administered Chitosan-N-acetylcysteine on Corneal Wound
Healing in a Rabbit Model.
AB - PURPOSE: The present study was performed to investigate the effect of topically
administered chitosan-N-acetylcysteine (C-NAC) on corneal wound healing in a
rabbit model. METHODS: A total of 20 New Zealand White rabbits were included in
the randomized, masked, placebo-controlled experiment. A monocular epithelial
debridement was induced by manual scraping under general anesthesia. Animals were
randomized to receive either C-NAC two times daily or placebo. Monitoring of
corneal wound healing was performed with ultra-high-resolution optical coherence
tomography (OCT) and epithelial fluorescein staining. Measurements were done
immediately after and up to 72 hours after wound induction. RESULTS: No
difference in wound size was found immediately after surgical debridement between
the C-NAC group and the placebo group. Wound healing was significantly faster in
the C-NAC group compared to the placebo group (p < 0.01 for both methods). A good
correlation was found between the OCT technique and the epithelial fluorescein
staining in terms of wound size (r = 0.94). CONCLUSIONS: Administration of C-NAC
containing eye drops twice daily leads to a faster corneal wound healing in a
rabbit model of corneal debridement as compared to placebo. Ultra-high-resolution
OCT is considered a noninvasive, dye-free alternative to conventional fluorescein
staining in assessing corneal wound healing also in humans.
PMID- 28695003
TI - Update on Diagnosis and Treatment of Diabetic Retinopathy: A Consensus Guideline
of the Working Group of Ocular Health (Spanish Society of Diabetes and Spanish
Vitreous and Retina Society).
AB - A group of members of the Spanish Retina and Vitreous Society (SERV) and of the
Working Group of Ocular Health of the Spanish Society of Diabetes (SED) updated
knowledge regarding the diagnosis and treatment of diabetic retinopathy (DR)
based on recent evidence reported in the literature. A synthesis of this
consensus forms the basis of the present review, which is intended to inform
clinicians on current advances in the field of DR and their clinical
applicability to patients with this disease. Aspects presented in this article
include screening procedures of DR, new technologies in the early diagnosis of
DR, control of risk factors in the different stages of the disease, indications
of panretinal laser photocoagulation, efficacy of intravitreal antiangiogenic
agents and steroids, and surgical options for treating DR-related complications.
Practical information regarding periodicity of screening procedures in patients
with type 1 and type 2 diabetes, ophthalmological controls according to the stage
of retinopathy and complications, and criteria and degree of urgency for referral
of a DR patient to the ophthalmologist are also presented.
PMID- 28695004
TI - Results of Femtosecond Laser-Assisted Descemet Stripping Automated Endothelial
Keratoplasty.
AB - PURPOSE: To evaluate femtosecond laser in DSAEK surgery as an improvement to
manual DSAEK. SETTINGS: Department of Ophthalmology, Cairo University. DESIGN: A
retrospective observational clinical study. METHODS: 20 eyes with SBK and Fuchs'
dystrophy underwent a Femto-assisted DSAEK by laser cutting of two matching
posterior stromal discs in the recipient and donor corneas and then fitting the
donor disc in the posterior corneal defect of the recipient using Busin's glide
or Terry forceps. RESULTS: Corneal thickness decreased significantly from a mean
of 900-micron preoperative values (900.7 m) to 562 m postoperatively. Evidence of
side healing was documented by OCT. One patient had a double AC, one patient had
an air interface entrapment "Double Bubble," one patient had a fungal infection
and was treated by a therapeutic penetrating keratoplasty, and one patient had a
CMO. CONCLUSION: Femtolaser-assisted DSAEK may be superior to manual techniques
as it offers better centration, thinner graft/host complex, earlier corneal
detergecense, and stronger healing. This study was registered at
Researchregistry.com with a UID: researchregistry2274.
PMID- 28695005
TI - The Association between Adiposity and the Risk of Glaucoma: A Meta-Analysis.
AB - PURPOSE: This meta-analysis was conducted to determine the potential association
between adiposity and glaucoma incidence. MATERIALS AND METHODS: A comprehensive
literature search was performed in PubMed and ISI Web of Science. A meta-analysis
was conducted using STATA software. RESULTS: Fifteen eligible studies involving
2,445,980 individuals were included to investigate the association between
adiposity and glaucoma incidence. The relative risks (RRs) were pooled with 95%
confidence intervals (CI) by using a random-effects model. The pooled RR between
adiposity and elevated intraocular pressure (IOP) was 1.73 (95% CI, 1.18-2.54),
whereas that between adiposity and open-angle glaucoma (OAG) was 0.97 (95% CI,
0.83-1.13). The pooled RR between abdominal adiposity and glaucoma was 1.28 (95%
CI, 1.15-1.41), whereas that between general adiposity and glaucoma was 1.09 (95%
CI, 0.87-1.37). Results of subgroup analysis by sex indicated the association
between adiposity and glaucoma in the female group (RR, 1.31; 95% CI, 1.05-1.64),
but not in the male group (RR, 1.11; 95% CI, 0.77-1.60). The pooled RR of cohort
studies and cross-sectional studies were 1.00 (95% CI, 0.84-1.20) and 1.22 (95%
CI, 0.89-1.66), respectively. CONCLUSIONS: Adiposity has a higher risk of
elevated IOP, and abdominal adiposity has a positive association with glaucoma,
especially in female patients.
PMID- 28695006
TI - Target Organ Damage and the Long Term Effect of Nonadherence to Clinical Practice
Guidelines in Patients with Hypertension: A Retrospective Cohort Study.
AB - BACKGROUND: There was limited published data on target organ damage (TOD) and the
effect of nonadherence to practice guidelines in Ethiopia. This study determined
TOD and the long term effect of nonadherence to clinical guidelines on
hypertensive patients. METHODS: An open level retrospective cohort study has been
employed at cardiac clinic of Gondar university hospital for a mean follow-up
period of 78 months. Multivariate Cox regression was conducted to test
associating factors of TOD. RESULTS: Of the total number of 612 patients
examined, the overall prevalence of hypertensive TOD was 40.3%. The presence of
comorbidities, COR = 1.073 [1.01-1.437], AOR = 1.196 [1.174-1.637], and
nonadherence to clinical practice guidelines, COR = 1.537 [1.167-2.024], AOR =
1.636 [1.189-2.251], were found to be predicting factors for TOD. According to
Kaplan-Meier analysis patients who were initiated on appropriate medication
tended to develop TOD very late: Log Rank [11.975 (p = 0.01)]. CONCLUSION: More
than forty percent of patients acquired TOD which is more significant. Presence
of comorbidities and nonadherence to practice guidelines were correlated with the
incidence of TOD. Appropriate management of hypertension and modification of
triggering factors are essential to prevent complications.
PMID- 28695007
TI - Preoperative Assessment of Patients Undergoing Elective Gastrointestinal Surgery:
Does Body Mass Index Matter?
AB - BACKGROUND: At Queen Elizabeth Hospital Birmingham (QEHB), no specific protocol
to stratify patients by body mass index (BMI) exists. This study sought to
evaluate outcomes following gastrointestinal surgery. METHODS: Patients
undergoing gastrointestinal surgery attending preassessment screening clinic
(PAS) from August to September 2016 at the QEHB were identified. Primary outcome
was postoperative complications. Secondary outcomes were major complications and
30-day readmission rates. RESULTS: Of 368 patients preassessed, 31% (116/368)
were overweight and 35% (130/368) were obese. Median age was 57 (range: 17-93).
There was no difference of BMI between the low risk and high risk clinics.
Patients in high risk clinic had significantly higher rates of comorbidities,
major surgical grades, and malignancy as the indication for surgery. Overall
complication rates were 14% (52/368), with 3% (10/368) having major complications
(Clavien-Dindo Grades III-IV). Whilst BMI was associated with comorbidity (p =
0.03) and ASA grade (p < 0.001), it was not associated with worse outcomes.
Patients attending high risk clinic had significantly higher rates of
complications. CONCLUSIONS: Surgery grade was found to be an independent risk
factor of complication rates. Use of BMI as an independent factor for
preassessment level is not justified from our cohort.
PMID- 28695008
TI - Dietary Strategies and Novel Pharmaceutical Approaches Targeting Serum ApoA-I
Metabolism: A Systematic Overview.
AB - The incidence of CHD is still increasing, which underscores the need for new
preventive and therapeutic approaches to decrease CHD risk. In this respect,
increasing apoA-I concentrations may be a promising approach, especially through
increasing apoA-I synthesis. This review first provides insight into current
knowledge on apoA-I production, clearance, and degradation, followed by a
systematic review of dietary and novel pharmacological approaches to target apoA
I metabolism. For this, a systematic search was performed to identify randomized
controlled intervention studies that examined effects of whole foods and
(non)nutrients on apoA-I metabolism. In addition, novel pharmacological
approaches were searched for, which were specifically developed to target apoA-I
metabolism. We conclude that both dietary components and pharmacological
approaches can be used to increase apoA-I concentrations or functionality. For
the dietary components in particular, more knowledge about the underlying
mechanisms is necessary, as increasing apoA-I per se does not necessarily
translate into a reduced CHD risk.
PMID- 28695009
TI - Prevalence and Clinical Spectrum of Liver Disease in Nepalese HIV-Sero-Positive
Patients Undergoing Antiretroviral Therapy: A Cross-Sectional Hospital Based
Study.
AB - INTRODUCTION: Liver enzyme abnormalities are common in HIV patients, and the
prevalence varies across the nations. In Nepal, however, prevalence of liver
enzyme disorder and the spectrum of these populations are lacking. OBJECTIVE: The
present study sheds light on prevalence and clinical spectrum of liver disease in
Nepalese HIV-sero-positive patients. METHODS: This cross-sectional study was
conducted at OPD/ART, Clinic of Bir Hospital, NAMS. One hundred and forty-four
HIV positive patients were enrolled consecutively and their clinical profiles of
liver injury were investigated. RESULTS: Of 144 recruited patients, liver enzyme
injury was observed in 82 (56.9%). Majority 61 (42.4%) of these cases had
hepatocellular type of liver injury. Opportunistic infections were reported in 18
cases, with 9 (6.2%) TB and 8 (5.6%) HCV. Test for significance of liver injury
confirmed the absence of any tendency towards an association with coinfection,
CD4 cells, ART regimen, and alcohol consumption (P > 0.05). However, gender
significantly linked with liver injury as well as the pattern of liver injury (P
< 0.05). CONCLUSION: The study revealed high rate of liver injury in a
substantial proportion of HIV individuals, stressing that a regular clinic follow
up is necessary for the HIV individuals who are undergoing ART.
PMID- 28695010
TI - Evaluation of Complication Rates after Breast Surgery Using Acellular Dermal
Matrix: Median Follow-Up of Three Years.
AB - INTRODUCTION: Acellular dermal matrices (ADMs) are now commonly used for breast
reconstruction surgery. There are various products available: ADMs derived from
human (HADM), porcine (PADM), or bovine (BADM) sources. Detailed long-term follow
up studies are necessary to detect differences in complication rates between
these products. MATERIAL AND METHODS: From 2010 to 2015, forty-one patients
underwent 52 ADM-breast reconstructions in our clinic, including oncologic breast
reconstructions and breast augmentation revisions (n = 52). 15x HADMs
(Epiflex(r)/DIZG), 21x PADMs (Strattice(r)/LifeCell), and 16x BADMs
(Tutomesh(r)/RTI Surgical) were implanted. Retrospective data collection with
median follow-up of 36 months (range: 12-54 months) was performed. RESULTS:
Overall complication rate was 17% after ADM implantation (HADM: 7%; PADM: 14%;
BADM: 31%). In a composite endpoint of complications and Red Breast Syndrome, a
lower event probability was observed between BADMs, PADMs, and HADMs (44%, 19%,
and 7%, resp.; p = 0.01 for the trend). Furthermore, capsular contracture
occurred in 6%, more frequently as compared to the current literature.
CONCLUSIONS: When ADM-based reconstruction is indicated, the authors suggest
primarily the use of HADMs and secondary the use of PADMs. It is shown that BADMs
have the highest complication probability within our patient cohort;
nevertheless, BADMs convey physical advantages in terms of flexibility and better
aesthetic outcomes. The indication for the use of ADMs should be filled for each
case individually.
PMID- 28695011
TI - Impact of Pharmacist Counselling on Clozapine Knowledge.
AB - Clozapine is the only antipsychotic with evidence for efficacy in treatment of
resistant schizophrenia but it carries a high side effect burden. Patient
information is provided but may be poorly retained. This study aims to examine
the impact of pharmacist counselling upon patient knowledge of clozapine.
Outpatients, aged 18 years and over, attending St. Patrick's University Hospital,
Dublin, participated in this study between June and August 2015. The intervention
consisted of pharmacist counselling on two occasions one month apart. Knowledge
was assessed using a 28-point checklist devised from the currently available
clozapine patient information sources, at baseline and after each counselling
session. Ethics approval was obtained. Twenty-five participants (40% female; mean
age 45.1 years, SD 9.82; 64% unemployed, 28% smokers) showed an improvement in
knowledge scores of clozapine from baseline to postcounselling on each occasion
with an overall improvement in knowledge score, from baseline to postcounselling
at one month, of 39.43%; p < 0.001. This study adds to the evidence that
interventions involving pharmacist counselling can improve patient knowledge,
whilst the specific knowledge gained relating to recognition of side effects may
help patients towards more empowerment regarding their treatment.
PMID- 28695012
TI - Association of One-Step Nucleic Acid Amplification Detected Micrometastases with
Tumour Biology and Adjuvant Chemotherapy.
AB - One-step nucleic acid amplification (OSNA) is an intraoperative technique with a
high sensitivity and specificity for sentinel node assessment. The aim of this
study was to assess the impact of OSNA on micrometastases detection rates and use
of adjuvant chemotherapy. A retrospective review of patients with sentinel node
micrometastases over a five-year period was carried out and a comparison of
micrometastases detection using OSNA and H&E techniques was made. Out of 1285
patients who underwent sentinel node (SLN) biopsy, 76 patients had
micrometastases. Using H&E staining, 36 patients were detected with SLN
micrometastases (9/year) in contrast to 40 patients in the OSNA year (40/year) (p
< 0.0001), demonstrating a fourfold increase with the use of OSNA. In the OSNA
group, there was also a proportional increase in Grade III, triple-negative, ER
negative, and HER-2-positive tumours being diagnosed with micrometastases. Also
on interactive PREDICT tool, the number of patients with a predicted 10-year
survival benefit of more than 3% with adjuvant chemotherapy increased from 52 to
70 percent. OSNA has resulted in an increased detection rate of micrometastases
especially in patients with aggressive tumour biology. This increased the number
of patients who had a predicted survival benefit from adjuvant chemotherapy.
PMID- 28695013
TI - Evaluation of Serum Posaconazole Concentrations in Patients with Hematological
Malignancies Receiving Posaconazole Suspension Compared to the Delayed-Release
Tablet Formulation.
AB - Posaconazole (PCZ) is frequently used for prophylaxis against invasive fungal
infections (IFI) in patients undergoing induction chemotherapy for acute myeloid
leukemia (AML) or myelodysplastic syndrome (MDS). Posaconazole is commercially
available as an oral suspension (PCZ-susp) and as a delayed-release tablet (PCZ
tab). Differences in absorption and bioavailability between these formulations
may result in variability in serum posaconazole concentrations. The primary
objective of this retrospective analysis was to compare attainment of goal serum
posaconazole steady state concentrations (Css) >= 700 ng/ml in patients with
AML/MDS undergoing induction chemotherapy receiving PCZ-susp 600-800 mg per day
(N = 118) versus PCZ-Tablet 300 mg twice daily for one day, followed by 300 mg
daily (N = 64). Sixty-two patients (97%) in the PCZ-tab group compared to 20
patients (17%) in the PCZ-susp group achieved goal Css (P < 0.0001). Median
posaconazole serum Css was 1,665 ng/ml (522-3,830 mg/ml) in the PCZ-tab group
versus 390 ng/ml (51-1,870 ng/ml) in the PCZ-susp group (P < 0.0001). There was
no difference in hepatotoxicity, QTc prolongation, or breakthrough IFI. Patients
receiving PCZ-tab were significantly more likely to achieve goal Css and
demonstrated higher Css versus patients receiving PCZ-susp. Prospective studies
are needed to assess the potential correlation of serum concentrations with
efficacy and toxicity.
PMID- 28695014
TI - Impaired Hippocampal Glutamate and Glutamine Metabolism in the db/db Mouse Model
of Type 2 Diabetes Mellitus.
AB - Type 2 diabetes mellitus (T2DM) is a risk factor for the development of
Alzheimer's disease, and changes in brain energy metabolism have been suggested
as a causative mechanism. The aim of this study was to investigate the cerebral
metabolism of the important amino acids glutamate and glutamine in the db/db
mouse model of T2DM. Glutamate and glutamine are both substrates for
mitochondrial oxidation, and oxygen consumption was assessed in isolated brain
mitochondria by Seahorse XFe96 analysis. In addition, acutely isolated cerebral
cortical and hippocampal slices were incubated with [U-13C]glutamate and [U
13C]glutamine, and tissue extracts were analyzed by gas chromatography-mass
spectrometry. The oxygen consumption rate using glutamate and glutamine as
substrates was not different in isolated cerebral mitochondria of db/db mice
compared to controls. Hippocampal slices of db/db mice exhibited significantly
reduced 13C labeling in glutamate, glutamine, GABA, citrate, and aspartate from
metabolism of [U-13C]glutamate. Additionally, reduced 13C labeling were observed
in GABA, citrate, and aspartate from [U-13C]glutamine metabolism in hippocampal
slices of db/db mice when compared to controls. None of these changes were
observed in cerebral cortical slices. The results suggest specific hippocampal
impairments in glutamate and glutamine metabolism, without affecting
mitochondrial oxidation of these substrates, in the db/db mouse.
PMID- 28695015
TI - The Longevity of Hippocampus-Dependent Memory Is Orchestrated by the Locus
Coeruleus-Noradrenergic System.
AB - The locus coeruleus is connected to the dorsal hippocampus via strong fiber
projections. It becomes activated after arousal and novelty, whereupon
noradrenaline is released in the hippocampus. Noradrenaline from the locus
coeruleus is involved in modulating the encoding, consolidation, retrieval, and
reversal of hippocampus-based memory. Memory storage can be modified by the
activation of the locus coeruleus and subsequent facilitation of hippocampal long
term plasticity in the forms of long-term depression and long-term potentiation.
Recent evidence indicates that noradrenaline and dopamine are coreleased in the
hippocampus from locus coeruleus terminals, thus fostering neuromodulation of
long-term synaptic plasticity and memory. Noradrenaline is an inductor of
epigenetic modifications regulating transcriptional control of synaptic long-term
plasticity to gate the endurance of memory storage. In conclusion, locus
coeruleus activation primes the persistence of hippocampus-based long-term
memory.
PMID- 28695016
TI - Identification of TMPRSS3 as a Significant Contributor to Autosomal Recessive
Hearing Loss in the Chinese Population.
AB - Hereditary hearing loss is characterized by a high degree of genetic
heterogeneity. Mutations in the TMPRSS3 (transmembrane protease, serine 3) gene
cause prelingual (DFNB10) or postlingual (DFNB8) deafness. In our previous study,
three pathogenic mutations in TMPRSS3 were identified in one Chinese family. To
evaluate the importance of TMPRSS3 mutations in recessive deafness among the
Chinese, we screened 150 autosomal recessive nonsyndromic hearing loss (ARNSHL)
families and identified 6 that carried seven causative TMPRSS3 mutations,
including five novel mutations (c.809T>A, c.1151T>G, c.1204G>A, c.1244T>C, and
c.1250G>A) and two previously reported mutations (c.323-6G>A and c.916G>A). Each
of the five novel mutations was classified as severe, by both age of onset and
severity of hearing loss. Together with our previous study, six families were
found to share one pathogenic mutation (c.916G>A, p.Ala306Thr). To determine
whether this mutation arose from a common ancestor, we analyzed six short tandem
repeat (STR) markers spanning the TMPRSS3 gene. In four families, we observed
linkage disequilibrium between p.Ala306Thr and STR markers. Our results indicate
that mutations in TMPRSS3 account for about 4.6% (7/151) of Chinese ARNSHL cases
lacking mutations in SLC26A4 or GJB2 and that the recurrent TMPRSS3 mutation
p.Ala306Thr is likely to be a founder mutation.
PMID- 28695018
TI - Takotsubo Cardiomyopathy after Spinal Anesthesia for a Minimally Invasive
Urologic Procedure.
AB - We present the case of a patient who suffered from Takotsubo cardiomyopathy (TCM)
immediately after the initiation of subarachnoid anesthesia for a minimally
invasive urologic procedure (tension-free vaginal tape (TVT) surgery for stress
urine incontinence). TCM mimics acute coronary syndrome and is caused by an
exaggerated sympathetic reaction to significant emotional or physical stress. Our
patient suffered from chest pain, palpitations, dyspnea, and hemodynamic
instability immediately following subarachnoid anesthesia and later in the
postanesthesia care unit. Blood troponin was elevated and new
electrocardiographic changes appeared indicative of cardiac ischemia. Cardiac
ultrasound indicated left ventricular apical akinesia and ballooning with
severely affected contractility. The patient was admitted to coronary intensive
care for the proper care and finally was discharged. TCM was attributed to high
emotional preoperative stress for which no premedication had been administered to
the patient. In conclusion, adequate premedication and anxiety management are not
only a measure to alleviate psychological stress of surgical patients, but, more
importantly, an imperative mean to suppress sympathetic nerve system response and
its cardiovascular consequences.
PMID- 28695019
TI - First Reported Case of Hemopericardium Related to Dabigatran Use Reversed by New
Antidote Idarucizumab.
AB - Dabigatran, the first novel oral anticoagulant (NOAC) with a reversal agent,
heralded a paradigm shift in the treatment of nonvalvular atrial fibrillation.
The potential for life-threatening hemorrhagic events with the use of NOACs has
been highly debated since the effectiveness of reversal agents such as
idarucizumab is based primarily on pharmacologic data. It is known that cancer
patients are at an increased risk of bleeding with anticoagulation, though
specific studies demonstrating the risks or efficacy of NOACs in this population
are lacking. We provide the first report of hemopericardium resulting in
multiorgan failure related to dabigatran use that was successfully reversed by
idarucizumab in a man with prostate cancer on chemotherapy.
PMID- 28695020
TI - Nasolabial Cyst: A Case Report with Ultrasonography and Magnetic Resonance
Imaging Findings.
AB - Nasolabial cysts are uncommon nonodontogenic lesions that occur in the nasal alar
region. These lesions usually present with asymptomatic swelling but can cause
pain if infected. In this case report, we describe the inadequacy of conventional
radiography in a nasolabial cyst case, as well as the magnetic resonance imaging
(MRI) and ultrasonography (US) findings in a 54-year-old female patient.
PMID- 28695021
TI - Clinical Comparison of the Subepithelial Connective Tissue versus Platelet-Rich
Fibrin for the Multiple Gingival Recession Coverage on Anterior Teeth Using the
Tunneling Technique.
AB - The aim of this study was to evaluate and compare, clinically, the efficiency of
the subepithelial connective tissue graft (SCTG) and platelet-rich fibrin (L-PRF)
using the tunnel technique to cover the multiple gingival recessions on anterior
teeth, in the same patient. Within the limits of this study, we conclude that
both SCTG and L-PRF proved to be reliable options for the treatment of gingival
recessions, efficiently supporting the biological and aesthetic demand,
stimulating the periodontal tissues' health, and bringing reliable and highly
predictable results.
PMID- 28695017
TI - Lifestyle Modulators of Neuroplasticity: How Physical Activity, Mental
Engagement, and Diet Promote Cognitive Health during Aging.
AB - The number of the elderly across the globe will approximate 2.1 billion by 2050.
Juxtaposed against this burgeoning segment of the population is evidence that
nonpathological aging is associated with an increased risk for cognitive decline
in a variety of domains, changes that can cause mild disability even before the
onset of dementia. Given that pharmacological treatments that mitigate dementia
are still outstanding, alternative therapeutic options are being investigated
increasingly. The results from translational studies have shown that modifiable
lifestyle factors-including physical activity, cognitive engagement, and diet-are
a key strategy for maintaining brain health during aging. Indeed, a multiplicity
of studies has demonstrated relationships between lifestyle factors, brain
structure and function, and cognitive function in aging adults. For example,
physical activity and diet modulate common neuroplasticity substrates
(neurotrophic signaling, neurogenesis, inflammation, stress response, and
antioxidant defense) in the brain whereas cognitive engagement enhances brain and
cognitive reserve. The aims of this review are to evaluate the relationship
between modifiable lifestyle factors, neuroplasticity, and optimal brain health
during aging; to identify putative mechanisms that contribute positive brain
aging; and to highlight future directions for scientists and clinicians.
Undoubtedly, the translation of cutting-edge knowledge derived from the field of
cognitive neuroscience will advance our understanding and enhance clinical
treatment interventions as we endeavor to promote brain health during aging.
PMID- 28695022
TI - Photopheresis Provides Significant Long-Lasting Benefit in Nephrogenic Systemic
Fibrosis.
AB - Nephrogenic systemic fibrosis (NSF), previously known as nephrogenic fibrosing
dermopathy, is a rare complication of exposure to gadolinium-based contrast
agents in patients who have significantly decreased renal function.
Manifestations include fibrosis of the skin and other tissues. Effective
therapies are lacking. Photopheresis has been tried with variable rates of
improvement, and small numbers of cases (20 as of 2016) have been reported of NSF
patients treated with photopheresis. We report a case of patient with nephrogenic
systemic fibrosis who was treated with photopheresis and demonstrated significant
lasting improvements.
PMID- 28695023
TI - E. coli Sepsis: Red Flag for Colon Carcinoma-A Case Report and Review of the
Literature.
AB - We present an atypical case of newly diagnosed colon cancer and provide insight
into the infectious predispositions of E. coli bacteremia to the development of
colon adenocarcinoma. A 66-year-old female was admitted to the hospital with one
week symptoms of subjective fevers, chills, and lower back pain. Upon initial
evaluation, her temperature was 101 degrees Fahrenheit with a white count of
12,000 K/mm3. Initial septic workup was positive for E. coli bacteremia. The
patient was started on Aztreonam. Repeat blood culture 48 hours later was
negative for any growth. However, later during hospital stay blood culture was
repeated due to SIRS, which was positive again for E. coli. CT scan of the
chest/abdomen/pelvis with contrast revealed no signs of colitis. Without clear
etiology for recurrent E. coli bacteremia ultimately colonoscopy was performed
which showed an ulcerated mass in the cecum. Biopsy showed moderately
differentiated adenocarcinoma. E. coli strains B2 and D produce cyclomodulin
toxins as part of their virulence, which interferes with the cell cycle
regulation, promoting chromosomal instability, and increasing susceptibility to
cancer. In patients with recurrent E. coli bacteremia with an unknown source,
colonoscopy should be done to look for colon cancer.
PMID- 28695024
TI - Vertebral Artery Thrombosis in Chronic Idiopathic Thrombocytopenic Purpura.
AB - INTRODUCTION: Immune thrombocytopenic purpura (ITP) is an autoimmune
hematological disorder that causes decreased production and destruction of
platelets leading to thrombocytopenia. Although thrombocytopenia usually causes
hemorrhagic problems, thrombotic events like strokes, although rare, can still
occur. Management of thrombotic events in patients with ITP differs from that of
patients with normal platelet count function and count. CASE DESCRIPTION: A 32
year-old female with a history of ITP presented with ischemic stroke. The patient
was treated in the hospital with IV immunoglobulin, discharged to a
rehabilitation facility, and had complete resolution of symptoms when examined at
a follow-up visit 3 months later. CONCLUSION: Although stroke in patients with
ITP is very rare due to thrombocytopenia, it has been reported in several other
published cases and is likely associated with increased platelet microparticle
levels, a byproduct of platelet destruction. While usage of antiplatelet therapy
in such patients is debated, immunosuppression therapy has been the mainstay
treatment in all published cases.
PMID- 28695025
TI - Sustained Remission in Patients with Primary Immune Thrombocytopenia after
Romiplostim Tapering and Discontinuation: A Case Series in Real Life Management
in Spain.
AB - Romiplostim, a thrombopoietin-receptor agonist (TPO-ra), is a highly effective
option in primary immune thrombocytopenia (ITP), with 80-90% of patients
achieving platelet responses after few weeks of treatment. The evidence showing
remissions, that is, sustained platelet counts after romiplostim discontinuation,
in patients with ITP refractory to immunosuppressive therapy is steadily
increasing. However, there is a lack of guidelines or recommendations addressing
how and when to taper romiplostim in clinical practice in patients maintaining
elevated and stable platelet counts. Furthermore, given the high heterogeneity of
ITP patients, no associated predictive factors have been currently identified.
Here, we present 4 representative clinical cases of the daily clinical practice
in Spain comprising newly diagnosed, persistent, and both splenectomized and
nonsplenectomized chronic ITP patients treated with romiplostim, achieving and
maintaining clinical remission (platelet count >= 50 * 109/L for 24 consecutive
weeks in the absence of any treatment for ITP) after treatment tapering and
discontinuation, without observed safety concerns. Prospective studies
identifying clinical and biological predictive factors of sustained response are
warranted.
PMID- 28695026
TI - Extensive Bone Marrow Necrosis: Initial Presentation in Sickle Cell Anemia-A Case
Report and Review of the Literature.
AB - Bone marrow necrosis (BMN) is a rare clinical entity that was first described in
an autopsy of a sickle cell disease (SCD) patient and is defined as ill-defined
necrotic cells in an amorphous eosinophilic background with preservation of
cortical bone. The pathophysiology of BMN is not well known; however, occlusion
of the bone marrow microcirculation with subsequent hypoxia and cell injury has
been thought to be common underlying features. Malignancy has been identified to
be the primary cause in 90% of the cases whereas SCD was found in only 2%. In
this report we present an unusual case of SCD with late onset of the disease
whose initial presentation was extensive BMN. The patient was not known
previously to have SCD, when suddenly she presented with severe cytopenias and
marked elevation in serum lactate dehydrogenase (LDH). Bone marrow examination
was done to exclude bone marrow infiltration, and BMN with dilated marrow sinuses
full of irreversibly sickled cells were the unexpected findings. Patients with a
mild SCD phenotype are at high risk of BMN. Thus, a high index of suspicion must
be borne in mind, particularly in an area of high SCD prevalence, to recognize
and prevent this catastrophic complication.
PMID- 28695027
TI - Systemic Amyloidosis and Cardiac Autonomic Neuropathy Associated with
Waldenstrom's Macroglobulinemia.
AB - A 73-year-old male with long-standing Waldenstrom's macroglobulinemia complicated
with systemic amyloidosis presented with a witnessed syncopal episode. He had
complaints of orthostatic dizziness and palpitations for few months. Orthostatic
hypotension and peripheral neuropathy were demonstrated on physical examination.
EKG, 24-hour Holter monitoring, and 2D echocardiogram were unremarkable. MRI of
the brain ruled out stroke. Patients with amyloidosis can develop cardiovascular
disease through amyloid cardiomyopathy, small vessel disease, conduction defects,
pericardial effusion, or autonomic denervation. After ruling out other life
threatening causes, Ewing's battery of tests was done to rule out cardiac
autonomic neuropathy. Two heart rate tests and one blood pressure test were
abnormal which indicated severe cardiac autonomic neuropathy. Cardiac autonomic
neuropathy can mask symptoms of acute coronary syndrome and hence early diagnosis
using the simple bedside maneuver is beneficial. The test is also important for
prognostication. Absence of augmentation of cardiac output from inadequate
autonomic stimulation will lead to postural hypotension, exercise intolerance,
and tachycardia. There may be no change in heart rate with Valsalva or deep
breathing both of which increase parasympathetic tone. As the condition
progresses, it may result in cardiac denervation which can result in silent
myocardial infarction, syncope, and sudden death.
PMID- 28695028
TI - Acquired von Willebrand Syndrome in IgM Monoclonal Gammopathy as the Presentation
of Lymphoplasmacytic Lymphoma.
AB - Acquired von Willebrand syndrome (AVWS) is an increasingly recognized entity with
numerous potential underlying etiologies. Most commonly implicated are
lymphoproliferative, myeloproliferative, cardiovascular, and autoimmune
disorders. Unlike inherited von Willebrand disease (vWD), AVWS tends to present
at an older age and without a family history of vWD. Treatment is directed at the
underlying etiology if one is uncovered, as well as treatment and prevention of
bleeding. Here, we present a rare case of AVWS secondary to Waldenstrom
macroglobulinemia which went unrecognized for several years but resolved promptly
with treatment. The potential mechanisms of AVWS secondary to monoclonal
gammopathies are discussed as well as strategies to treat and prevent bleeding in
these patients.
PMID- 28695029
TI - Differential Diagnosis and Management of Incomplete Locked-In Syndrome after
Traumatic Brain Injury.
AB - Locked-in syndrome (LIS) is a rare diagnosis in which patients present with
quadriplegia, lower cranial nerve paralysis, and mutism. It is clinically
difficult to differentiate from other similarly presenting diagnoses with no
standard approach for assessing such poorly responsive patients. The purpose of
this case is to highlight the clinical differential diagnosis process and
outcomes of a patient with LIS during acute inpatient rehabilitation. A 32-year
old female was admitted following traumatic brain injury. She presented with
quadriplegia and mutism but was awake and aroused based on eye gaze
communication. The rehabilitation team was able to diagnose incomplete LIS based
on knowledge of neuroanatomy and clinical reasoning. Establishing this diagnosis
allowed for an individualized treatment plan that focused on communication,
coping, family training, and discharge planning. The patient was ultimately able
to discharge home with a single caregiver, improving her quality of life.
Continued evidence highlights the benefits of intensive comprehensive therapy for
those with acquired brain injury such as LIS, but access is still limited for
those with a seemingly poor prognosis. Access to a multidisciplinary, specialized
team provides opportunity for continued assessment and individualized treatment
as the patient attains more medical stability, improving long-term management.
PMID- 28695030
TI - Placenta Percreta in a Gravid Bicornuate Unicollis Uterus.
AB - BACKGROUND: Identifying bicornuate uterus can be challenging especially as a
cause of early pregnancy bleeding. On ultrasonographic examination, it is
difficult to misdiagnose pregnancy in a bicornuate uterus as an ectopic pregnancy
due to the continuity of the endometrium. A rudimentary horn of a bicornuate
uterus in early pregnancy can occasionally be misdiagnosed for an ectopic
pregnancy especially when compounded by severe abdominal pains and supportive
sonographic evidence. Myometrial invasive grading of placenta may be necessary
for emergency preparedness and consenting. Hemihysterectomy is lifesaving when
percreta has caused severe postpartum haemorrhage. CASE PRESENTATION: We present
a 24-year-old primigravida who presented to the maternity department with severe
abdominal pains at 35 weeks. She was pale on clinical examination and
haemodynamically unstable. She underwent emergency caesarean section with a
preoperative diagnosis of concealed abruptio placentae. Intraoperatively we
encountered a bicornuate uterus, delivered a fresh stillbirth, and noted a
placenta percreta. A hemihysterectomy was done and she recovered after
transfusion without complications. CONCLUSION: A gravid horn of a bicornuate
uterus may present as an ectopic pregnancy; careful assessment at laparotomy or
laparoscopy is required to prevent inadvertent surgical termination of pregnancy.
Placental myometrial invasive assessment is important for delivery emergency
preparedness.
PMID- 28695031
TI - Traumatic Submacular Hemorrhage with Macular Hole Repaired by Pneumatic
Displacement and Intravitreal t-PA Injection.
AB - This paper presents a case demonstrating repair of traumatic macular hole and
submacular hemorrhage with intravitreal gas tamponade and t-PA in an office
setting.
PMID- 28695032
TI - Proximal Femoral Fracture in Hip Arthrodesis Treated with Double Reconstruction
Plates.
AB - We present a rare clinical case of a 90-year-old female who sustained a proximal
femoral neck fracture following long-standing hip arthrodesis. Since the fracture
occurred relatively proximally and involved the pelvis, double-plate fixation was
chosen to achieve rigid fixation. The reconstruction plate was placed at the
posterior and anterior columns individually through single vertical incision. She
was treated successfully, and she attained preinjury activity level. Proximal
femoral fractures in arthrodesed hips need to be recognized as a fracture between
the pelvis and femur. Rotational stress from the trunk and lower extremity
requires rigid fixation to minimize the increase of displacement and the risk for
nonunion.
PMID- 28695033
TI - A Rare Cause of Upper Airway Obstruction in a Child.
AB - Ventricular band cyst is a rare condition in children but can result in severe
upper airway obstruction with laryngeal dyspnea or death. The diagnosis should be
considered in any stridor in children with previous history of intubation or
respiratory infections. We report a case of a 4-year-old girl, received in an
array of severe respiratory distress, emergency endoscopy was done, and a large
ventricular tape band cyst obstructing the air way was found. Complete excision
was made, and postoperative prophylaxis tracheotomy was done. The postoperative
course was uneventful with improvement of clinical and endoscopic signs.
PMID- 28695034
TI - Adult ADHD: Questioning Diagnosis and Treatment in a Patient with Multiple
Psychiatric Comorbidities.
AB - Adult Attention-Deficit/Hyperactivity Disorder (ADHD) is a contentious diagnostic
issue, which has been increasing in prevalence in recent years, and is often
comorbid with other psychiatric disorders. This report presents a detailed
account of a clinical case involving a middle-aged man with a history of
recurrent depressive episodes and an unsubstantiated diagnosis of ADHD, treated
with stimulants. There is persistent debate around the use of psychostimulants
both in adult ADHD and in the treatment of depression. Despite promising
activating properties, psychostimulants carry significant risks of misuse and
substance use disorder. In this report, we consider the potential benefits and
adverse effects of stimulants in the treatment of adult ADHD and mood disorders
and review the learning points of this complicated, but not uncommon, clinical
case.
PMID- 28695035
TI - Psychosis Crisis Associated with Thyrotoxicosis due to Graves' Disease.
AB - We present the case of a patient with previous psychiatric illness, acutely
exacerbated by thyroid storm due to Graves' disease, in whom treatment with
antipsychotics induced catatonia. These associations are extremely rare and may
be confused with Hashimoto's encephalopathy, especially in the presence of anti
thyroid antibodies in cerebrospinal fluid. The treatment consists in the control
of the triggering disease (in this case the resolution of the thyrotoxicosis) and
the use of benzodiazepines. However, in some cases, the resolution of psychiatric
symptoms is partial and may require the use of electroconvulsive therapy.
PMID- 28695036
TI - A Case Report of Mania and Psychosis Five Months after Traumatic Brain Injury
Successfully Treated Using Olanzapine.
AB - BACKGROUND: There are few published pharmacologic trials for the treatment of
acute mania following traumatic brain injury (TBI). To our knowledge, we present
the first case report of an individual being treated and stabilized with
olanzapine monotherapy for this condition. CASE PRESENTATION: We describe the
case of a 53-year-old African American male admitted to an inpatient psychiatric
hospital with one month of behavioral changes including irritability, decreased
need for sleep, hyperverbal speech, hypergraphia, and paranoia five months after
TBI. Using Diagnostic and Statistical Manual of Mental Disorders, 5th edition
(DSM-5) criteria, he was diagnosed with bipolar disorder due to traumatic brain
injury, with manic features. He was serially evaluated with clinical rating
scales to measure symptom severity. The Young Mania Rating Scale (YMRS) score
upon admission was 31, and the Clinician-Rated Dimensions of Psychosis Symptom
Severity (CRDPSS) score was initially 9. After eight days of milieu treatment and
gradual titration of olanzapine to 15 mg nightly, his symptoms completely abated,
with YMRS and CRDPSS scores at zero on the day of discharge. CONCLUSION:
Olanzapine was effective and well tolerated for the treatment of mania following
TBI.
PMID- 28695037
TI - NXP-2 Positive Dermatomyositis: A Unique Clinical Presentation.
AB - Dermatomyositis (DM), a myopathy associated with inflammation and muscle
weakness, has historically been difficult to diagnose. Recently, nuclear matrix
protein (NXP-2) antibodies have been described as a myositis-specific antibody
that may aid in the diagnostic evaluation. We present the case of a 21-year-old,
previously healthy, African American male with DM. He presented to our outpatient
clinic with periorbital swelling and a rash, for which he was started on
prednisone by an ophthalmologist. Towards the end of the prednisone taper, he
began to experience muscle weakness, a worsening rash, and dysphagia to solids
with a resultant loss of 60 pounds within a month. He was transferred to a
tertiary care hospital where he was further evaluated and ultimately diagnosed
with dermatomyositis, supported by skin and muscle biopsies, and was found to be
positive for NXP-2. He was given intravenous immunoglobulin (IVIG) and high-dose
steroids with improvement.
PMID- 28695038
TI - Does Dopamine Depletion Trigger a Spreader Lexical-Semantic Activation in
Parkinson's Disease? Evidence from a Study Based on Word Fluency Tasks.
AB - It has been hypothesised that, in Parkinson's disease (PD), dopamine might
modulate spreading activation of lexical-semantic representations. We aimed to
investigate this hypothesis in individuals with PD without dementia by assessing
word frequency and typicality in verbal fluency tasks. We predicted that the
average values of both of these parameters would be lower in PD patients with
respect to healthy controls (HC). We administered letter-cued and category-cued
fluency tasks to early PD patients in two experimental conditions: the tasks were
administered both after 12-18 hours of dopaminergic stimulation withdrawal ("OFF"
condition) and after the first daily dose of dopaminergic therapy ("ON"
condition). HC were also given the two tasks in two conditions with the same
intersession delay as PD patients but without taking drugs. Results showed that
in both OFF and ON treatment conditions PD patients did not differ from HC in
word frequency or typicality. Moreover, in the PD group, no significant
difference was found between the experimental conditions. Our results show that
semantic spreading was not altered in the PD sample examined; this suggests that
in early PD the functioning of the semantic system is relatively independent from
the activity of dopamine brain networks.
PMID- 28695039
TI - Economic Burden Analysis of Parkinson's Disease Patients in China.
AB - BACKGROUND AND OBJECTIVE: Parkinson's Disease (PD) is a progressive
neurodegenerative disorder, which is prevalent in people over 65 years old. PD
reduces patients' quality of life and exerts a heavy economic burden on patients
and their families. The purpose of this research is to identify the costs of PD
and to evaluate the economic distribution of medical care for PD patients in
China. METHODS: A professional survey was administered to 116 patients with PD.
Records of medical cost were reviewed. Direct and indirect costs were analyzed.
The main cost-driving factors of PD were identified using multivariate regression
analysis. RESULTS: The average annual cost per PD patient in China is $3,225.94,
with direct and indirect costs accounting for $2,503.46 and $722.48,
respectively. Direct costs consist of $556.27 for surgery, $44.67 for appointment
fees, $605.67 for prescription medication, $460.29 for hospitalization, $71.03
for auxiliary examination, $35.64 for transportation, $10.39 for special
equipment, and $719.50 for formal care. The total cost is closely related to
surgical treatment, dopamine agonist, and levodopa costs. CONCLUSION: The cost of
PD patients in China is considerable and exceeds average economic capacity,
especially antiparkinson medication and caring costs. This study may provide a
reference for PD healthcare optimization in the future.
PMID- 28695040
TI - Supercritical Fluid Chromatography of Drugs: Parallel Factor Analysis for Column
Testing in a Wide Range of Operational Conditions.
AB - Retention mechanisms involved in supercritical fluid chromatography (SFC) are
influenced by interdependent parameters (temperature, pressure, chemistry of the
mobile phase, and nature of the stationary phase), a complexity which makes the
selection of a proper stationary phase for a given separation a challenging step.
For the first time in SFC studies, Parallel Factor Analysis (PARAFAC) was
employed to evaluate the chromatographic behavior of eight different stationary
phases in a wide range of chromatographic conditions (temperature, pressure, and
gradient elution composition). Design of Experiment was used to optimize
experiments involving 14 pharmaceutical compounds present in biological and/or
environmental samples and with dissimilar physicochemical properties. The results
showed the superiority of PARAFAC for the analysis of the three-way (column *
drug * condition) data array over unfolding the multiway array to matrices and
performing several classical principal component analyses. Thanks to the PARAFAC
components, similarity in columns' function, chromatographic trend of drugs, and
correlation between separation conditions could be simply depicted: columns were
grouped according to their H-bonding forces, while gradient composition was
dominating for condition classification. Also, the number of drugs could be
efficiently reduced for columns classification as some of them exhibited a
similar behavior, as shown by hierarchical clustering based on PARAFAC
components.
PMID- 28695041
TI - A Machine Learning and Cross-Validation Approach for the Discrimination of
Vegetation Physiognomic Types Using Satellite Based Multispectral and
Multitemporal Data.
AB - This paper presents the performance and evaluation of a number of machine
learning classifiers for the discrimination between the vegetation physiognomic
classes using the satellite based time-series of the surface reflectance data.
Discrimination of six vegetation physiognomic classes, Evergreen Coniferous
Forest, Evergreen Broadleaf Forest, Deciduous Coniferous Forest, Deciduous
Broadleaf Forest, Shrubs, and Herbs, was dealt with in the research. Rich-feature
data were prepared from time-series of the satellite data for the discrimination
and cross-validation of the vegetation physiognomic types using machine learning
approach. A set of machine learning experiments comprised of a number of
supervised classifiers with different model parameters was conducted to assess
how the discrimination of vegetation physiognomic classes varies with
classifiers, input features, and ground truth data size. The performance of each
experiment was evaluated by using the 10-fold cross-validation method. Experiment
using the Random Forests classifier provided highest overall accuracy (0.81) and
kappa coefficient (0.78). However, accuracy metrics did not vary much with
experiments. Accuracy metrics were found to be very sensitive to input features
and size of ground truth data. The results obtained in the research are expected
to be useful for improving the vegetation physiognomic mapping in Japan.
PMID- 28695042
TI - Pharmacological manipulations of autophagy modulate paraquat-induced cytotoxicity
in PC12 cells.
AB - Environmental exposure to paraquat has been reported to be associated with
Parkinson's disease (PD). In experimental animal models paraquat reproduces
features of PD, however, the exact mechanism of PD-induced neurotoxicity has not
been fully established. This study was designed to investigate paraquat-mediated
interference with mitochondrial function and autophagy, and determine the impact
of the modulation of autophagy flux on paraquat-induced cell toxicity. Rat
adrenal pheochromocytoma PC12 cells were treated with paraquat for 24 h to
establish a cellular mode of PD induced neurotoxicity. Pre-incubation of PC12
cells with an antioxidant N-acetyl-L-cysteine (NAC) or autophagy modulators
rapamycin and chloroquine was conducted to determine the effect of modulation of
oxidative status and autophagy flux on paraquat-elicited cytotoxicity.
Mitochondrial functions and dynamics were analyzed by measuring oxygen
consumption in a high-resolution oxygraph and imaging with a fluorescent
mitochondrial dye (MitoTracker). Reactive oxygen species was determined by flow
cytometry using fluorescent probe DCFH-DA. Autophagic flux was determined by
Western blot analysis of autophagy marker LC3-II as well as p62 expression. It
was found that treatment of cells with paraquat caused a concentration-dependent
loss of cell viability that was accompanied by a decrease in cell respiration and
reduction of polarized mitochondria, which was prevented by pretreatment of cells
with NAC. Analysis of autophagy showed that NAC inhibited basic autophagy flux of
PC12 cells, as evidenced by a decrease in LC3-II level and an increase in p62
expression. However, this modulation of autophagy by NAC may not be implicated
into its cellular protective mechanism over paraquat cytotoxicity as inhibition
of autophagy by chloroquine significantly enhanced paraquat induced cytotoxicity.
Furthermore, the autophagy inducer rapamycin dramatically decreased paraquat
induced cellular toxicity in PC12 cells. The present study demonstrates that
basal autophagy plays a protective role in paraquat-induced cell toxicity.
Antioxidant NAC confers protective role in paraquat toxicity mainly through
maintaining mitochondrial dynamics and function, other than a modulation of
autophagy flux.
PMID- 28695043
TI - Nonspastic hemifacial spasm confirmed by abnormal muscle responses.
AB - BACKGROUND: Hemifacial spasm is usually diagnosed by inspection which mainly
identifies involuntary movements of orbicularis oculi. Assessing abnormal muscle
responses (AMR) is another diagnostic method. CASE DESCRIPTION: We report a case
of left hemifacial spasm without detectable involuntary facial movements. The
patient was a 48-year-old man with a long history of subjective left facial
twitching. On magnetic resonance imaging (MRI), the left VIIth cranial nerve was
compressed by the left anterior inferior cerebellar artery (AICA), which was in
turn compressed by the left vertebral artery. We initially treated him with
botulinum toxin. We were able to record AMR, and hemifacial spasm occurred after
AMR stimulation, although no spasm was detectable by inspection. Subsequently, we
performed microvascular decompression with transposition of the AICA that
compressed the VIIth cranial nerve. His hemifacial spasm resolved by 5 weeks
after surgery and was not induced by AMR stimulation. CONCLUSION: Hemifacial
spasm can sometimes be diagnosed by detecting AMR rather than by visual
inspection. We propose that such hemifacial spasm should be termed nonspastic
hemifacial spasm.
PMID- 28695044
TI - Neuro-Behcet disease mimicking brain tumor: A case report.
AB - BACKGROUND: Behcet's disease (BD) is an inflammatory multisystem disease with
unknown etiology, and consists of a TRIAD comprising recurrent oral ulcers,
genital ulcers, and uveitis. In some cases, the disease affects the central
nervous system, called Neuro-Behcet Disease (NBD). Few cases of NBD simulating a
brain tumor have been previously reported. CASE DESCRIPTION: Here, we describe
the case of a 46-year-old male patient with a previous diagnosis of brain tumor
who was later diagnosed for BD. CONCLUSION: This case highlights the importance
of differential diagnosis of lesions with tumoral features. Checking for the
possibility of NBD may help avoiding biopsy in these types of cases.
PMID- 28695045
TI - A modified transcondylar screw to accommodate anatomical skull base variations.
AB - BACKGROUND: Occipitocervical instability may be attributed to congenital,
bony/ligamentous abnormalities, trauma, neoplasm, degenerative bone disease, and
failed atlantoaxial fixation. Indications for occipitocervical fixation include
the prevention of disabling pain, cranial nerve dysfunction, paralysis, or even
sudden death. METHODS: The screw trajectory for the modified transcondylar screw
(mTCS) is optimally planned utilizing a three-dimensional skull reconstructed
image. RESULTS: The modified mTCS technique is helpful where there is a loss of
bone, such as after prior suboccipital craniotomy and/or an inadequate occipital
condyle. The new proposed technique is similar to the classical transcondylar
screw placement but follows a deeper course along the bony lip of foramen magnum
toward clivus from a dorsolateral approach. CONCLUSION: The modified mTCS
technique allows for direct visualization and, therefore, helps to avoid damage
to the hypoglossal nerve and lateral aspect of brain stem.
PMID- 28695046
TI - Long-term effect of surgical revascularization on silent microbleeds in adult
moyamoya disease: A case report.
AB - BACKGROUND: Recent development of magnetic resonance (MR) imaging has shown that
silent microbleeds can be observed in a certain subgroup of adult patients with
moyamoya disease. The patients with microbleeds are at higher risk for
hemorrhagic stroke. However, the beneficial effects of surgical revascularization
have not been established in asymptomatic patients with moyamoya disease. The
authors present a case that underwent surgical revascularization for asymptomatic
moyamoya disease because the number of silent microbleeds increases on serial MR
examinations. CASE DESCRIPTION: A 61-year-old female was referred to our hospital
because of nonspecific headache. T2-weighted MR imaging revealed silent
microbleeds in the corpus callosum. She was diagnosed as moyamoya disease on
cerebral angiography. She was conservatively followed up, however, de novo
microbleeds developed in the right temporal and frontal lobes on follow-up MR
imaging 6 months later. Superficial temporal artery to middle cerebral artery
(STA-MCA) anastomosis and indirect bypass were performed on the right side to
prevent hemorrhagic stroke. Postoperative course was uneventful. Follow-up
cerebral angiography performed 10 months after surgery showed a marked
development of surgical collateral through both direct and indirect bypass and
the diminishment of moyamoya vessels. For the last 7 years after surgery, she is
free from any cerebrovascular events, and serial MR examinations revealed no
further development of de novo microbleeds. CONCLUSIONS: Surgical
revascularization may be useful to reduce the moyamoya vessels and prevent
cerebrovascular events in a certain subgroup of patients with asymptomatic
moyamoya disease, although its universal benefits on asymptomatic moyamoya
disease have not been established yet.
PMID- 28695047
TI - Validation of reference genes in human chordoma.
AB - BACKGROUND: Chordoma are rare slow-growing tumors of the axial skeleton, which
are thought to arise from remnants of the notochord. Little is known about the
underlying mechanisms that drive this tumor. However, the assessment of gene
expression levels by quantitative real-time polymerase chain reaction (qRT-PCR)
is hampered due to a lack of validated reference genes. Using an unstable
reference gene in qRT-PCR may lead to irreproducible results. METHODS: The
expression of 12 candidate reference genes (ACTB, B2M, T, EF1a, GAPDH, HPRT,
KRT8, KRT19, PGK1, RS27a, TBP, and YWHAZ) was analyzed by qRT-PCR in flash frozen
chordoma samples from 18 patients. GeNorm and NormFinder algorithms were used to
rank the stability of the genes. RESULTS: From most to least stably expressed,
the top six genes found by geNorm were PGK1, YWHAZ, ACTB, HPRT, EF1A, and TBP.
When analyzed by NormFinder, the top six genes were ACTB, YWHAZ, PGK1, B2M, TBP,
and HPRT. GAPDH alone, which is often used as a reference gene in chordoma gene
expression studies, is not stable enough for reliable results. CONCLUSION: In
gene expression studies of human chordomas, PGK1, ACTB, and YWHAZ are more stably
expressed, and therefore, are preferred reference genes over the most often used
reference gene so far, GAPDH.
PMID- 28695048
TI - Primary pituitary neuroendocrine tumor: Case report and literature review.
AB - BACKGROUND: Neuroendocrine tumors (NET) originate from the diffuse neuroendocrine
system. These can arise in almost every organ of the body, although they are most
commonly found in the gastrointestinal tract and respiratory system. The skull
base and sellar region are extremely rare sites for neuroendocrine carcinoma.
Consequently, in this case, both diagnosis and definition of surgical goals, as
well as further treatment strategies were challenging. CASE DESCRIPTION: A 65
year-old woman was admitted to our Neurosurgery Department with a rapidly
progressive visus reduction, drowsiness, polyuria, and polydipsia. Neuroimaging
showed a sellar/suprasellar mass (diameter of 2 cm) with a heterogeneous signal
compressing the optic chiasm and extending laterally toward the cavernous sinus.
Differential diagnosis based on imaging included pituitary macroadenoma or
metastasis. The patient underwent endoscopic endonasal transsphenoidal surgery. A
total resection of the mass was impossible because of the infiltration of the
optic chiasm and the intraoperative histological diagnosis of malignant
epithelial neoplasm. Further histological evaluation revealed that the lesion was
a NET with no other primary or metastatic sites detectable. Subsequently, the
patient was successfully treated with fractioned stereotactic radiotherapy and
polychemotherapy. Four years after the surgery, follow-up magnetic resonance
imaging showed stability of the residual disease. Neurologic examination revealed
a complete visual recovery. CONCLUSIONS: Primary pituitary NET, though rare,
should be included in the differential diagnosis of sellar lesions. A
multimodality treatment approach is needed. Finally, the present case highlights,
that in the case of a pituitary lesion infiltrating the optic chiasm, including
NET, the endoscopic endonasal transsphenoidal subtotal resection followed by
fractioned stereotactic radiotherapy and chemotherapy may represent an effective
and safe choice of treatment.
PMID- 28695049
TI - Metastasis to a spinal meningioma.
AB - BACKGROUND: Metastasis of one cancer to another is rare. Here, we report a spinal
meningioma that was infiltrated by metastatic deposits from another cancer. CASE
DESCRIPTION: A 62-year-old male presented with a progressive spastic paraparesis.
Magnetic resonance (MR) imaging of the spine suggested a well-defined intradural
extramedullary (IDEM) T8 mass in the dorsal spinal canal. When excised, it proved
histologically to be a meningothelial meningioma infiltrated by metastatic
deposits from an adenocarcinoma. CONCLUSION: Tumor to tumor metastasis rarely
occurs, and meningioma, owing to its biological character and increased
vascularity, is one of the most common recipients of a metastases from other
lesions.
PMID- 28695050
TI - Rapid intracranial pressure drop as a cause for posterior reversible
encephalopathy syndrome: Two case reports.
AB - BACKGROUND: Posterior reversible encephalopathy syndrome (PRES) is characterized
by reversible edematous lesions on radiological examinations as well as symptoms
of altered consciousness and seizures. To date, the underlying mechanism remains
largely unknown. CASE DESCRIPTIONS: Case 1 is a 72-year-old man with a history of
hypertension presented with a subarachnoid hemorrhage. Fourteen days after the
successful clipping of a ruptured aneurysm; he experienced inadvertent
overdrainage via the intraventricular drain. Nine hours later, he started to have
seizures followed by disturbances in consciousness. An emergency magnetic
resonance imaging showed multiple high-intensity lesions in the frontal,
temporal, parietal, and occipital lobes, basal ganglia, brainstem, and cerebellar
hemispheres bilaterally, which are compatible with typical magnetic resonance
findings in PRES patients. He was treated conservatively and recovered well. Case
2 is a 68-year-old woman with a mild history of hypertension and a ventriculo
peritoneal shunt for obstructive hydrocephalus, who underwent a cysto-peritoneal
shunt placement because of an enlarging symptomatic arachnoid cyst. Immediately
following surgery, she experienced disturbances in consciousness and developed
status epilepticus. Radiological examinations revealed remarkable shrinkage of
the arachnoid cyst and multiple edematous lesions, which led us to strongly
suspect PRES. With conservative treatment, her symptoms and the radiological
abnormalities disappeared. CONCLUSION: Based on the previous literature and our
cases, we believe that the association between rapid reduction of intracranial
pressure (ICP) and the development of PRES should be recognized because most
neurosurgical procedures such as craniotomy or cerebrospinal fluid diversion
present a potential risk of rapid reduction of ICP.
PMID- 28695051
TI - Smaller outer diameter of atherosclerotic middle cerebral artery associated with
RNF213 c.14576G>A Variant (rs112735431).
AB - BACKGROUND: Intracranial atherosclerosis (ICAS) involves diverse histologies and
several remodeling patterns. Ring finger protein 213 (RNF213) c.14576G>A variant
(rs112735431), recently reported to be associated with ICAS, may be linked with
negative remodeling (outer diameter - reducing morphological alteration) of
intracranial arteries. This study investigated the outer diameter of
atherosclerotic middle cerebral artery (MCA). METHODS: Patients with unilateral
atherosclerotic MCA stenosis/occlusion were enrolled in this single-hospital
based case-control study at The University of Tokyo Hospital. The patients were
divided into two groups by the presence of RNF213 c.14576G>A (variant group and
wild-type group) and the outer diameter of the MCA was measured with high
resolution magnetic resonance imaging. RESULTS: Twenty-eight patients with the
wild type and 19 patients with the variant type were included. The outer diameter
of the stenotic side MCA was smaller in the variant group than in the wild-type
group (P = 8.3 * 10-6). The outer diameter of the normal side MCA was also
smaller in the variant group than in the wild-type group (P = 5.2 * 10-3). The
ratio of stenotic side to normal side was also smaller in the variant group than
in the wild-type group (P = 1.5 * 10-5). CONCLUSIONS: This study indicates that
RNF213 c.14576G>A is associated with negative remodeling of ICAS.
PMID- 28695052
TI - Recurrent symptomatic vertebral hemangioma during two consecutive pregnancies:
Case report and review of the literature.
AB - BACKGROUND: Pregnancy-related changes can exacerbate the symptoms/signs of
vertebral hemangiomas. Here, we report a patient who experienced symptomatic
vertebral hemangiomas resulting in cord compression during two consecutive
pregnancies. CASE DESCRIPTION: A 28-year-old female 34 weeks pregnant, presented
with a progressive spastic paraparesis. Magnetic Resonance Imaging (MRI)
demonstrated an T5 vertebral body signal change attributed to a hemangioma
resulting in cord compression. Following a cesarean section, she had a trans
thoracic T5 corpectomy with spinal fusion. Indeed, the histopathology was
consistent with a vertebral hemangioma. She fully recovered after this first
surgery. However, six years later, she again presented with a spastic paraparesis
and sphincter deficit now 29 weeks pregnant. The MR demonstrated cord compression
one more at the T5 level attributed to the hemangioma; following a T5 and T6
laminectomy, the left paracentral epidural vascular mass totally resected. Her
child was successfully delivered 2 months later at which point she exhibited only
mild residual lower limb spasticity. CONCLUSION: Patients with known vertebral
hemangiomas should be closely monitored during pregnancy as increased growth
during these pregnancies may result in progressive spinal cord compression.
PMID- 28695053
TI - Aging is protective against pressure overload cardiomyopathy via adaptive
extracellular matrix remodeling.
AB - When challenged by hemodynamic stress, aging hearts respond differently to young
hearts. Preclinical models of heart disease should take into account the effects
of age. However, in the transverse aortic constriction (TAC) model of pressure
overload cardiomyopathy, the larger aorta of aging mice has not previously been
taken into account. First, we studied the aortic size in mice, and found that the
aortic cross-sectional area (CSA) is 28% larger in aging mice than in young adult
mice (P=0.001). We then performed TAC to make the same proportional reduction in
CSA in young and aging mice. This produced the same pressure gradient across the
constriction and the same rise in B-type natriuretic peptide expression. Young
mice showed acute deterioration in systolic function assessed by pressure-volume
loops, progressive LV remodeling on echocardiography, and a 50% mortality at 12
weeks post-TAC. In contrast, aging mice showed no acute deterioration in systolic
function, much less ventricular remodeling and were protected from death. Aging
mice also showed significantly increased levels of matrix metalloproteinase-3
(MMP-3; 3.2 fold increase, P<0.001) and MMP-12 (1.5-fold increase, P<0.001),
which were not seen in young mice. Expression of tissue inhibitor of MMP-1 (TIMP
1) increased 8.6-fold in aging hearts vs 4.3-fold in young hearts (P<0.01). In
conclusion, following size-appropriate TAC, aging mice exhibit less LV remodeling
and lower mortality than young adult mice. This is associated with induction of
protective ECM changes.
PMID- 28695054
TI - Direct evidence of sympathetic hyperactivity in patients with vasospastic angina.
AB - BACKGROUND: The autonomic nervous system is reported to be involved in the
pathogenesis of vasospastic angina (VSA). Studies based on heart rate variability
analysis have shown conflicting results with both a reduction and an enhancement
of sympathetic nervous system (SNS) activity in patients with Prinzmetal's
variant angina, but direct assessment has never been performed. The aim of our
study was to evaluate the SNS activity using microneurography in patients with
VSA. METHODS AND RESULTS: The SNS was evaluated by measuring the muscle
sympathetic nerve activity (MSNA) with microneurography in 15 patients with VSA
confirmed by positive ergonovine provocation test and 15 controls subjects
negative for the provocation test. Over the baseline period, SNS activity was
higher in patients with VSA compared with control patients (56.8 +/- 5 vs. 49.3
+/- 6.3 burst/min, p < 0.001, respectively). During mental stress, SNS activity
increased significantly only in patients with VSA, which still presented a higher
SNS activity than control patients (66.1 +/- 7.2 vs. 53.6 +/- 8.7 burst/min; p <
0.001, respectively). Furthermore only VSA patients showed significant
hemodynamic modifications with an increase in mean arterial blood pressure (96.2
+/- 13.4 vs. 86.6 +/- 9.6 mmHg in VSA patients and control subjects,
respectively; p < 0.05). CONCLUSION: Our results provide the first direct
evidence of lasting increased sympathetic activity that is worsened by mental
stress in patients with VSA. These results suggest that SNS participate to the
pathogenesis of VSA by enhancing coronary vascular tone.
PMID- 28695055
TI - The application of early goal directed therapy in patients during burn shock
stage.
AB - Early goal directed therapy (EGDT) provided at the earliest stages of burn shock,
has significant benefits for ordinary burn patients, however, its effect on
patients with more than 80% of total surface area burned (TBSA) still remains
unclear. In this study, 34 extensively burned patients with (87.3+/-5.6)% of
total surface area burned were collected from January 2008 to January 2014. All
burn patients here had similar monitoring or treatment modalities. Of these 34
burn patients, 13 patients were treated with EGDT under pulse indicator
continuous cardiac output (PICCO) monitoring, and 21 patients were treated with
conventional fluid management. Information obtained in the course of treatment
included mean arterial pressure (MAP), central venous oxygen saturation (ScvO2),
oxygenation index (PaO2/FiO2), blood lactic acid and urine volume, infusion
volume (mL.1% TBSA-1.Kg-1), complications of over-resuscitation (hydrothorax or
pulmonary edema), case rate of burn sepsis and fatality. Our results demonstrated
that there existed significant difference between the two groups in parameters
below: 1. Higher ScvO2 (%) after EGDT (EGDT: 78.1+/-8.6, CG: 65.5+/-11.2; t=
3.446, P<0.05), 2. Higher PaO2/FiO2 after EGDT (EGDT: 381.4+/-56.6, CG: 328.9+/
48.6; t=2-875, P<0.05), 3. Lower mean infusion volume after EGDT (mL.1% TBSA-1.Kg
1) (EGDT: 3.29+/-0.26, CG: 3.71+/-0.31; t=5.292, P<0.05), 4. Lower complications
of over-resuscitation after EGDT (EGDT: 2/13, CG: 15/21; P<0.05); However, no
statistical significance existed in parameters below: 1. MAP (EGDT: 76.2+/-13.1,
CG: 74.3+/-15.6; t=-0.36, P>0.05), 2. Urine volume (EGDT: 0.83+/-0.12, CG: 0.85+/
0.17; t=0.370, P>0.05), 3. Case of burn sepsis (EGDT: 13/13, CG: 20/21; P=1), 4.
Case fatality (EGDT: 1/13, CG: 3/21; P=1). The finding results showed that
patients with more than 80% of total surface area burned during burn shock phase
could get better outcome from EGDT.
PMID- 28695056
TI - Severe vitamin D deficiency affects the expression of autophagy related genes in
PBMCs and T-cell subsets in active systemic lupus erythematosus.
AB - We aimed to investigate whether vitamin D levels affect the expression of
autophagy related genes (Atgs) and the counts of T-cell subsets in active
systemic lupus erythematosus (SLE), as well as to assess the association between
Atgs and T-cell subsets. Serum levels of 25(OH)D3, Atgs and T-cell subsets were
measured in 50 patients with active SLE. Serum 25(OH)D3 levels <10 ng/ml and 10
30 ng/ml were defined as severe vitamin D deficiency and vitamin D insufficiency,
respectively. Comparisons were made between values of severe vitamin D deficiency
and vitamin D insufficiency patients, and the correlations between Atgs in PBMCs
and T-cell subsets were carried out. mTOR mRNA levels were higher (P=0.036) and
LC3 mRNA levels were lower (P<0.001) in severe vitamin D deficiency group
compared to vitamin D insufficiency group. The counts of CD4+ T cells and the
CD4/CD8 ratio were significantly higher in severe vitamin D deficiency group
compared to vitamin D insufficiency group (P=0.001, P<0.001,respectively). LC3
mRNA levels correlated negatively with CD4+ T cells counts (r=-0.302, P=0.033),
while correlated positively with CD8+ T cells counts (r=0.299, P=0.035). Serum
25(OH)D3 levels correlated negatively with the counts of CD4+ T cells (r=-0.423,
P=0.002) and correlated positively with the counts of CD8+ T cells (r=0.318,
P=0.024). Our results suggested that severe vitamin D deficiency affected the
expression of Atgs in PBMCs and T-cell subsets in active SLE, indicating that
vitamin D may affect T-cell subsets via regulating autophagy.
PMID- 28695057
TI - Effects of peritoneal macrophage autophagy on the immune function of sepsis mice.
AB - OBJECTIVE: To investigate the effect of peritoneal macrophage autophagy on immune
function in sepsis mice. METHODS: Seventy-two male BALB/C mice were
intraperitoneally injected with LPS to induce sepsis. The mice were randomly
divided into six groups: LPS+2 h, LPS+6 h, LPS+12 h, LPS+24 h and LPS+36 h. LPS
with a dose of 10 mg/kg was intraperitoneally injected into the abdominal cavity
of the sepsis mice, and the control group was injected with the same dose of
saline. ELISA was used to detect the concentrations of inflammatory factors IL-2,
IL-10 and TNF-alpha in the peripheral blood, and the CD4+T/CD8+T ratio in the
peripheral blood was detected by flow cytometry. The expression levels of LC3II
and Beclin-1/beta-action in the mouse macrophages were measured using Western
blot to determine the level of autophagy. RESULTS: The expression levels of LC3II
and Beclin-1 were significantly higher in the peritoneal macrophages of the mice
from the LPS+2 h group than in those of the mice from the normal group (P<0.05).
Meanwhile, these levels continuously declined in the LPS+6 h, LPS+12 h, LPS+24 h
and LPS+36 h groups (P<0.05). The peripheral blood CD4+T/CD8+T cell ratio was
significantly higher in the LPS+2 h and LPS+6 h groups than in the normal group
(P<0.05). The ratio peaked at 6 h and then continuously declined (P<0.05).
Furthermore, the concentrations of IL-2 and Tnf-alpha were significantly higher
in the peripheral blood serum of the LPS+2 h, LPS+6 h and LPS+12 h groups than in
those of the normal group (P<0.05). The peak was observed at 12 h followed by a
continuous decline in the LPS+24 h and 3 LPS+6 h groups (P<0.05). The peripheral
serum IL-10 concentration was significantly higher in the LPS+2 h, LPS+6 h,
LPS+12 h, LPS+24 h and LPS+36 h groups than in the normal group (P<0.05). In the
LPS+6 h, LPS+12 h, LPS+24 h and LPS+36 h groups, the peritoneal macrophages
LC3II, Beclin-1 and peripheral serum CD+4T/CD+8T ratio correlation index R2=0.716
(P=0.043), R2=0.954 (P=0.023). CONCLUSION: Autophagy in peritoneal macrophages
plays an important role in the immune function of sepsis mice. In addition, the
autophagy of peritoneal macrophages and the immune function of sepsis mice are
strongly correlated. Furthermore, macrophage autophagy plays an important role in
the immune function changes in sepsis mice, and the underlying mechanism may be
involved in inflammation and macrophage antigen presentation by regulating the
secretion of inflammatory cytokines and lymphocyte apoptosis antagonism.
PMID- 28695058
TI - The chemokine CCL28 is elevated in the serum of patients with celiac disease and
decreased after treatment.
AB - Accumulating evidence show that many inflammatory cytokines are involved in
pathophysiology of celiac disease (CD). CCL28 known as mucosa associate
epithelial chemokine (MEC) is produced by mucosa and chemoattracts IgA-producing
B cells into the mucosa. However, its levels in patients with CD have not yet
been elucidated. CCL28 levels and anti-tTTG (IgA) were detected in the serum of
28 new cases of CD, 32 cases of treated patents and 32 normal individuals by
Elisa. Moreover, the effect of gluten on intestinal cells, Caco-2, was examined
by RT-PCR. Our data show that (i) the levels of CCL28 is significantly higher in
patients with CD than normal individuals, (ii) CCL28 levels is reduced in
patients with CD who had gluten-free diets. Accordingly, we observed that CCL28
expression is upregulated in a dose-dependent manner when the Caco-2 cells were
cultured in the presence of gluten. In conclusion, gluten enhances CCL28
expression and that CCL28 could be a novel biomarker for diagnosis and following
up the patients with CD. However, further investigation in a larger number of
patients is required.
PMID- 28695060
TI - Can levodopa prevent cognitive decline in patients with Parkinson's disease?
AB - Cognitive impairment in Parkinson's disease (PD) will become more important since
the number of elderly patients with PD is increasing. We prospectively studied
non-demented patients with PD over the course of 3 years to identify factors
associated with PD that contribute to a decline in cognitive function. From among
100 consecutive patients, we registered 79 patients with PD. A total of 55
patients completed the study during 3 years and were divided to two groups:
patients with a decline in cognitive function and those without a decline in
cognitive function after 3 years. Seventeen independent variables were evaluated
with the use of logistic regression models. The increase in the daily levodopa
dose was related to a decline in cognitive function on univariate logistic
regression analysis (OR = 0.279, p = 0.024, 95% CI = 0.092-0.848). Other
variables were not related to a decline in cognitive function. The increase in
the daily dose of levodopa was greater in patients without a decline in cognitive
function than those with a decline in cognitive function; on the other hand, the
cognitive function unchanged. Our results suggest that the treatment with
levodopa might prevent a decline in cognitive function in PD.
PMID- 28695059
TI - B7-H3 role in the immune landscape of cancer.
AB - The field of immunotherapy is a continually expanding niche in cancer biology
research. In the last two decades, there has been significant progress in
identifying better targets and creating more specific agents for therapy in the
field. B7-H3 (CD276) is an immune checkpoint from the B7 family of molecules,
many of whom interact with known checkpoint markers including CTLA4, PD-1, and
CD28. This is an exciting molecule that is overexpressed in many cancers,
although the receptor of B7-H3 has not been characterized. Initially, B7-H3 was
thought to co-stimulate the immune response, but recent studies have shown that
it has a co-inhibitory role on T-cells, contributing to tumor cell immune
evasion. Therefore, its overexpression has been linked to poor prognosis in human
patients and to invasive and metastatic potential of tumors in in vitro models.
Moreover, recent evidence has shown that B7-H3 influences cancer progression
beyond the immune regulatory roles. In this review, we aim to characterize the
roles of B7-H3 in different cancers, its relationship with other immune
checkpoints, and its non-immunological function in cancer progression. Targeting
B7-H3 in cancer treatment can reduce cell proliferation, progression, and
metastasis, which may ultimately lead to improved therapeutic options and better
clinical outcomes.
PMID- 28695061
TI - Altered mechanisms of protein synthesis in frontal cortex in Alzheimer disease
and a mouse model.
AB - Expression of the nucleolar chaperones nucleolin (NCL) and nucleophosmin (NPM1),
upstream binding transcription factor (UBTF), rRNA18S, rRNA28S, and several genes
encoding ribosomal proteins (RPs) is decreased in frontal cortex area 8 at
advanced stages of Alzheimer's disease (AD). This is accompanied by reduced
protein levels of elongation factors eEF1A and eEF2. Changes are more marked in
AD cases with rapid course (rpAD), as initiation factor eIF3eta is significantly
down-regulated and several RP genes up-regulated in rpAD when compared with
typical AD. These changes contrast with those seen in APP/PS1 transgenic mice
used as a model of AD-like beta-amyloidopathy; Ncl mRNA, rRNA18S, rRNA28S and
seven out of fifteen assessed RP genes are up-regulated in APP/PS1 mice aged 20
months; only eEF2 protein levels are reduced in transgenic mice. Our findings
show marked altered expression of molecules linked to the protein synthesis
machinery from the nucleolus to the ribosome in frontal cortex at terminal stages
of AD which differs from that seen in APP/PS1 transgenic mice, thus further
suggesting that molecular signals in mouse models do not apply to real human
disease counterparts.
PMID- 28695062
TI - Susceptibility-Based Neuroimaging: Standard Methods, Clinical Applications, and
Future Directions.
AB - The evaluation of neuropathologies using MRI methods that leverage tissue
susceptibility have become standard practice, especially to detect blood products
or mineralization. Additionally, emerging MRI techniques have the ability to
provide new information based on tissue susceptibility properties in a robust and
quantitative manner. This paper discusses these advanced susceptibility imaging
techniques and their clinical applications.
PMID- 28695063
TI - How PET/MR Can Add Value For Children With Cancer.
AB - PURPOSE: To review how PET/MR technology could add value for pediatric cancer
patients. RECENT FINDINGS: Since many primary tumors in children are evaluated
with MRI and metastases are detected with PET/CT, integrated PET/MR can be a time
efficient and convenient solution for pediatric cancer staging. 18F-FDG PET/MR
can assess primary tumors and the whole body in one imaging session, avoid
repetitive anesthesia and reduce radiation exposure compared to 18F-FDG PET/CT.
This article lists 10 action points, which might improve the clinical value of
PET/MR for children with cancer. However, even if PET/MR proves valuable, it
cannot enter mainstream applications if it is not accessible to the majority of
pediatric cancer patients. Therefore, innovations are needed to make PET/MR
scanners affordable and increase patient throughput. SUMMARY: PET/MR offers
opportunities for more efficient, accurate and safe diagnoses of pediatric cancer
patients. The impact on patient management and outcomes has to be substantiated
by large-scale prospective clinical trials.
PMID- 28695064
TI - Information and decision-making needs of psychiatric patients: the perspective of
relatives.
AB - BACKGROUND: Mental illness may strongly affect relatives' lives. Therefore, it is
important to empower relatives by providing health information according to their
preferences. METHODS: An online cross-sectional survey was conducted using a
purpose-designed questionnaire on online health information and decision-support
needs. RESULTS: Prevalent reasons for online health information search of the 185
participating relatives were the need for general information and the
insufficiency of the information given by the health care provider. The most
difficult treatment decisions concerned the treatment setting (inpatient or
outpatient) as well as the psychopharmacological treatment. DISCUSSION: Since
psychiatric patients' relatives report extensive information and decision-support
needs, it is essential to address their needs in health information material.
Assessment of relatives' needs when developing health information materials is
recommended.
PMID- 28695065
TI - 13C based proteinogenic amino acid (PAA) and metabolic flux ratio analysis of
Lactococcus lactis reveals changes in pentose phosphate (PP) pathway in response
to agitation and temperature related stresses.
AB - Lactococcus lactis subsp. cremoris MG1363 is an important starter culture for
dairy fermentation. During industrial fermentations, L. lactis is constantly
exposed to stresses that affect the growth and performance of the bacterium.
Although the response of L. lactis to several stresses has been described, the
adaptation mechanisms at the level of in vivo fluxes have seldom been described.
To gain insights into cellular metabolism, 13C metabolic flux analysis and gas
chromatography mass spectrometry (GC-MS) were used to measure the flux ratios of
active pathways in the central metabolism of L. lactis when subjected to three
conditions varying in temperature (30 degrees C, 37 degrees C) and agitation
(with and without agitation at 150 rpm). Collectively, the concentrations of
proteinogenic amino acids (PAAs) and free fatty acids (FAAs) were compared, and
Pearson correlation analysis (r) was calculated to measure the pairwise
relationship between PAAs. Branched chain and aromatic amino acids, threonine,
serine, lysine and histidine were correlated strongly, suggesting changes in flux
regulation in glycolysis, the pentose phosphate (PP) pathway, malic enzyme and
anaplerotic reaction catalysed by pyruvate carboxylase (pycA). Flux ratio
analysis revealed that glucose was mainly converted by glycolysis, highlighting
the stability of L. lactis' central carbon metabolism despite different
conditions. Higher flux ratios through oxaloacetate (OAA) from pyruvate (PYR)
reaction in all conditions suggested the activation of pyruvate carboxylate
(pycA) in L. lactis, in response to acid stress during exponential phase.
Subsequently, more significant flux ratio differences were seen through the
oxidative and non-oxidative pentose phosphate (PP) pathways, malic enzyme, and
serine and C1 metabolism, suggesting NADPH requirements in response to
environmental stimuli. These reactions could play an important role in
optimization strategies for metabolic engineering in L. lactis. Overall, the
integration of systematic analysis of amino acids and flux ratio analysis
provides a systems-level understanding of how L. lactis regulates central
metabolism under various conditions.
PMID- 28695066
TI - Predicting suitable habitat of the Chinese monal (Lophophorus lhuysii) using
ecological niche modeling in the Qionglai Mountains, China.
AB - Understanding the distribution and the extent of suitable habitats is crucial for
wildlife conservation and management. Knowledge is limited regarding the natural
habitats of the Chinese monal (Lophophorus lhuysii), which is a vulnerable
Galliform species endemic to the high-montane areas of southwest China and a good
candidate for being an umbrella species in the Qionglai Mountains. Using
ecological niche modeling, we predicted current potential suitable habitats for
the Chinese monal in the Qionglai Mountains with 64 presence points collected
between 2005 and 2015. Suitable habitats of the Chinese monal were associated
with about 31 mm precipitation of the driest quarter, about 15 degrees C of
maximum temperature of the warmest month, and far from the nearest human
residential locations (>5,000 m). The predicted suitable habitats of the Chinese
monal covered an area of 2,490 km2, approximately 9.48% of the Qionglai
Mountains, and was highly fragmented. 54.78% of the suitable habitats were under
the protection of existing nature reserves and two conservation gaps were found.
Based on these results, we provide four suggestions for the conservation
management of the Chinese monal: (1) ad hoc surveys targeting potential suitable
habitats to determine species occurrence, (2) more ecological studies regarding
its dispersal capacity, (3) establishment of more corridors and green bridges
across roads for facilitating species movement or dispersal, and (4) minimization
of local disturbances.
PMID- 28695067
TI - GeNNet: an integrated platform for unifying scientific workflows and graph
databases for transcriptome data analysis.
AB - There are many steps in analyzing transcriptome data, from the acquisition of raw
data to the selection of a subset of representative genes that explain a
scientific hypothesis. The data produced can be represented as networks of
interactions among genes and these may additionally be integrated with other
biological databases, such as Protein-Protein Interactions, transcription factors
and gene annotation. However, the results of these analyses remain fragmented,
imposing difficulties, either for posterior inspection of results, or for meta
analysis by the incorporation of new related data. Integrating databases and
tools into scientific workflows, orchestrating their execution, and managing the
resulting data and its respective metadata are challenging tasks. Additionally, a
great amount of effort is equally required to run in-silico experiments to
structure and compose the information as needed for analysis. Different programs
may need to be applied and different files are produced during the experiment
cycle. In this context, the availability of a platform supporting experiment
execution is paramount. We present GeNNet, an integrated transcriptome analysis
platform that unifies scientific workflows with graph databases for selecting
relevant genes according to the evaluated biological systems. It includes GeNNet
Wf, a scientific workflow that pre-loads biological data, pre-processes raw
microarray data and conducts a series of analyses including normalization,
differential expression inference, clusterization and gene set enrichment
analysis. A user-friendly web interface, GeNNet-Web, allows for setting
parameters, executing, and visualizing the results of GeNNet-Wf executions. To
demonstrate the features of GeNNet, we performed case studies with data retrieved
from GEO, particularly using a single-factor experiment in different analysis
scenarios. As a result, we obtained differentially expressed genes for which
biological functions were analyzed. The results are integrated into GeNNet-DB, a
database about genes, clusters, experiments and their properties and
relationships. The resulting graph database is explored with queries that
demonstrate the expressiveness of this data model for reasoning about gene
interaction networks. GeNNet is the first platform to integrate the analytical
process of transcriptome data with graph databases. It provides a comprehensive
set of tools that would otherwise be challenging for non-expert users to install
and use. Developers can add new functionality to components of GeNNet. The
derived data allows for testing previous hypotheses about an experiment and
exploring new ones through the interactive graph database environment. It enables
the analysis of different data on humans, rhesus, mice and rat coming from
Affymetrix platforms. GeNNet is available as an open source platform at
https://github.com/raquele/GeNNet and can be retrieved as a software container
with the command docker pull quelopes/gennet.
PMID- 28695068
TI - Screening of phospholipase A activity and its production by new actinomycete
strains cultivated by solid-state fermentation.
AB - Novel microbial phospholipases A (PLAs) can be found in actinomycetes which have
been poorly explored as producers of this activity. To investigate microbial PLA
production, efficient methods are necessary such as high-throughput screening
(HTS) assays for direct search of PLAs in microbial cultures and cultivation
conditions to promote this activity. About 200 strains isolated with selected
media for actinomycetes and mostly belonging to Streptomyces (73%) and
Micromonospora (10%) genus were first screened on agar-plates containing the
fluorophore rhodamine 6G and egg yolk phosphatidylcholine (PC) to detect strains
producing phospholipase activity. Then, a colorimetric HTS assay for general PLA
activity detection (cHTS-PLA) using enriched PC (~60%) as substrate and cresol
red as indicator was developed and applied; this cHTS-PLA assay was validated
with known PLAs. For the first time, actinomycete strains were cultivated by
solid-state fermentation (SSF) using PC as inductor and sugar-cane bagasse as
support to produce high PLA activity (from 207 to 2,591 mU/g of support).
Phospholipase activity of the enzymatic extracts from SSF was determined using
the implemented cHTS-PLA assay and the PC hydrolysis products obtained, were
analyzed by TLC showing the presence of lyso-PC. Three actinomycete strains of
the Streptomyces genus that stood out for high accumulation of lyso-PC, were
selected and analyzed with the specific substrate 1,2-alpha-eleostearoyl-sn
glycero-3-phosphocholine (EEPC) in order to confirm the presence of PLA activity
in their enzymatic extracts. Overall, the results obtained pave the way toward
the HTS of PLA activity in crude microbial enzymatic extracts at a larger scale.
The cHTS-PLA assay developed here can be also proposed as a routine assay for PLA
activity determination during enzyme purification,directed evolution or
mutagenesis approaches. In addition, the production of PLA activity by
actinomycetes using SSF allow find and produce novel PLAs with potential
applications in biotechnology.
PMID- 28695069
TI - Morphological connectivity correlates with trait impulsivity in healthy adults.
AB - BACKGROUND: Impulsivity is one crucial personality trait associated with various
maladaptive behavior and many mental disorders. In the study reported here, we
investigated the relationship between impulsivity and morphological connectivity
(MC) between human brain regions, a newly proposed measure for brain coordination
through the development and learning. METHOD: Twenty-four participants' T1
weighted magnetic resonance imaging (MRI) images and their self-reported
impulsivity scores, measured by the Barratt impulsiveness scale (BIS), were
retrieved from the OpenfMRI project. First, we assessed the MC by quantifying the
similarity of probability density function of local morphological features
between the anterior cingulate cortex (ACC), one of the most crucial hubs in the
neural network modulating cognitive control, and other association cortices in
each participant. Then, we correlated the MC to impulsivity scores across
participants. RESULTS: The BIS total score was found to correlate with the MCs
between the ACC and two other brain regions in the right hemisphere: the inferior
frontal gyrus (IFG), a well-established structure for inhibition control; the
inferior temporal gyrus (ITG), which has been previously shown to be associated
with hyperactive/impulsivity symptoms. Furthermore, the ACC-IFG MC was mainly
correlated with motor impulsivity, and the ACC-ITG MC was mainly correlated with
attentional impulsivity. DISCUSSION: Together, these findings provide evidence
that the ACC, IFG, and ITG in the right hemisphere are involved neural networks
modulating impulsivity. Also, the current findings highlight the utility of MC
analyses in facilitating our understanding of neural correlates of behavioral and
personality traits.
PMID- 28695070
TI - A new terrestrial snail species (Gastropoda: Bulimulidae) from the Region de
Antofagasta, northern Chile.
AB - A new species of Scutalus Albers, 1850 (Gastropoda: Bulimulidae), Scutalus chango
sp. n., is described from a coastal area of northern Chile. Empty shells of this
new species were found buried in sand and under boulders and rocks in the
foothills of the Chilean Coastal Range at Paposo, Region de Antofagasta. This new
species is distinguished from all other Chilean terrestrial snails by its slender
shell with a flared and reflected aperture, and by the presence of a columellar
fold. This is the first record of Scutalus in Chile, and the southernmost record
for this endemic South American bulimulid genus. The presence of this species in
Paposo highlights the need for further research and for conservation guidelines
in coastal areas of northern Chile, which have comparatively high levels of
biodiversity and endemism.
PMID- 28695071
TI - The role of acceptance and values in quality of life in patients with an acquired
brain injury: a questionnaire study.
AB - OBJECTIVE: An acquired brain injury (ABI) is a challenge for an individual's
quality of life (QOL). In several chronic illnesses acceptance has been found to
be associated with a better health-related quality of life. This study
investigated whether this relationship is also found in patients with ABI. We
also explored the impact of the perceived ability to live according to one's own
values (life-values-match). METHODS: A total of 68 individuals (18-65 years of
age) with an acquired brain injury completed a battery of questionnaires. The
relations between health-related QOL (SF-36) and disease specific QOL (EBIQ;
European Brain Injury Questionnaire), and personal values (Schwartz Values
Inventory) and acceptance (ICQ; Illness Cognitions Questionnaire) were
investigated. An additional question measured the life-values-match.
Rehabilitation professionals reported the extent of impairment involved. RESULTS:
Acceptance was positively associated with mental aspects of health-related QOL
and the EBIQ Core Scale, after demographic variables and the extent of impairment
were introduced in the regression. In a post hoc analysis we found that the life
values-match mediated the relationship between acceptance and mental aspects of
QOL. CONCLUSION: In patients with an ABI, promoting acceptance may be useful to
protect QOL. Strengthening the life-values-match may be a way to accomplish this.
PMID- 28695072
TI - Bilateral transient visual loss and meningeal irritation signs following
retrobulbar anesthesia.
AB - A 62-year-old man underwent an uneventful cataract surgery in the left eye
following retrobulbar anesthesia. Fifteen minutes after the surgery, the patient
had visual loss in his right (unoperated) eye, headache, dizziness, nausea, and
vomiting. The bandage on the left (operated) eye was removed and the initial
ophthalmic examination revealed bilateral dilated pupils with absence of light
perception. His fundus examination and vital signs were unremarkable.
Immediately, a computerized tomography (CT) was performed to scan both orbit and
brain. The orbit CT revealed air bubbles within the left optic nerve sheath,
which confirmed inadvertent injection and administration of anesthetic
medications into the optic nerve sheath. Within three hours, meningeal irritation
signs recovered spontaneously and visual acuity improved to 20/20 in the right
eye and 20/40 in the left eye.
PMID- 28695073
TI - Reconstruction of delayed scleral flap melting with bovine pericardium after
trabeculectomy with mitomycin C.
AB - Aim: To present a challenging case of hypotony after trabeculectomy and its
treatment. Case description: A 22-year-old woman with juvenile glaucoma underwent
a conventional trabeculectomy with mitomycin C on the right eye (OD). In the
immediate postoperative period, we observed a hyperfiltration bleb with hypotony
refractory to conservative measures leading to hypotony maculopathy. A surgical
revision with scleral flap resuture and conjunctival graft was performed with a
satisfactory result and resolution of hypotony maculopathy. After two years, the
patient complained of low visual acuity (VA) of the OD. During examination, we
observed a fine and avascular bleb with Seidel and visualization of the
underlying uveal tissue, an intraocular pressure (IOP) of 5 mmHg, and
chorioretinal folds. A new revision of the trabeculectomy was performed. During
the procedure, it was not possible to identify the scleral flap, so the fistula
was closed with a patch of collagenous membrane derived from bovine pericardium
(Tutopatch(r) graft). A good clinical evolution occurred. After 2 months, IOP was
15 mmHg without Seidel or changes in the fundus and VA was 20/20. After 8 months
of follow-up, the IOP remains stable without further complaints. Conclusion: This
case illustrates the difficulties faced in the management of a common
complication of trabeculectomy and highlights some of the options available for
its treatment. There are few reports of scleral melting after trabeculectomy.
However, trauma and scleral necrosis associated with mitomycin are listed as the
main causes. The use of a scleral patch derived from bovine pericardium allows
effective suturing and closure of the aqueous leak.
PMID- 28695074
TI - Inadvertent steroid injection into the crystalline lens.
AB - Intravitreal triamcinolone is administered for a wide number of vitreoretinal
conditions. Several complications including cataract formation, raised
intraocular pressure, and endophthalmitis have been reported following
intravitreal injections. We report a rare case wherein triamcinolone was
inadvertently injected directly into the crystalline lens. A 41-year-old male
presented to us with a history of intravitreal injection of triamcinolone in the
left eye 2 weeks earlier. Slit lamp examination revealed a needle tract in the
crystalline lens with steroid granules dispersed throughout the lens core. Such a
complication is extremely rare with only three cases reported previously.
PMID- 28695075
TI - Gaps in the Early Infant Diagnosis cascade in a high HIV prevalence setting.
PMID- 28695076
TI - HIV testing: the 'front door' to the UNAIDS 90-90-90 target.
PMID- 28695077
TI - Missing tuberculosis patients in the private sector: business as usual will not
deliver results.
PMID- 28695078
TI - Gastric aspiration: routine use for diagnosis of pulmonary tuberculosis patients
unable to expectorate sputum.
PMID- 28695079
TI - Early infant diagnosis and outcomes in HIV-exposed infants at a central and a
district hospital, Northern Malawi.
AB - Setting: Mzuzu Central Hospital (MZCH), Mzuzu, and Chitipa District Hospital
(CDH), Chitipa, Malawi. Objective: To compare management and outcomes of human
immunodeficiency virus (HIV) exposed infants in early infant diagnosis (EID)
programmes at MZCH, where DNA polymerase chain reaction (PCR) testing is
performed on site, and CDH, where samples are sent to MZCH, between 2013 and
2014. Design: Retrospective cohort study. Results: Of infants enrolled at MZCH (n
= 409) and CDH (n = 176), DNA PCR results were communicated to the children's
guardians in respectively 56% and 51% of cases. The median time from sample
collection to guardians receiving results was 34 days for MZCH and 56 days for
CDH. In both hospitals, only half of the dried blood spot (DBS) samples were
collected between 6 and 8 weeks. More guardians from MZCH than CDH received test
results within 1 month of sample collection (25% vs. 10%). Among the HIV-positive
infants, a higher proportion at MZCH (92%) started antiretroviral therapy than at
CDH (46%). The relative risk (RR) of death was higher among infants with late DBS
collection (RR 1.3, 95%CI 1.0-1.7) or no collection (RR 5.8, 95%CI 4.6-7.2), and
when guardians did not receive test results (RR 8.3, 95%CI 5.7-11.9). Conclusion:
EID programmes performed equally poorly at both hospitals, and might be helped by
point-of-care DNA PCR testing. Better programme implementation and active follow
up might improve infant outcome and retention in care.
PMID- 28695080
TI - Loss to follow-up among children in pre-ART care under the National AIDS
Programme, Tamil Nadu, South India.
AB - Setting: Children aged <15 years constitute 7% of all people living with the
human immunodeficiency virus (HIV) in India. A previous study from an
antiretroviral therapy (ART) centre in south India reported 82% loss to follow-up
(LTFU) among children in pre-ART care (2006-2011). Objective: To assess the
proportion of LTFU within 1 year of registration among HIV-infected children
(aged < 15 years) registered in all 43 ART centres in the state of Tamil Nadu,
India, during the year 2012. Design: This was a retrospective cohort study
involving a review of programme records. Results: Of 656 children registered for
HIV care, 20 (3%) were not assessed for ART eligibility. Of those remaining, 226
(36%) were not ART eligible and entered pre-ART care. Among these, at 1 year of
registration, 50 (22%) were LTFU, 40 (18%) were transferred out and 136 (60%)
were retained in care at the same centre. The child's age, sex, World Health
Organization stage or occurrence of opportunistic infection were not associated
with LTFU. Conclusion: One in five children registered under pre-ART care were
lost to follow-up. Stronger measures to prevent LTFU and reinforce retrieval
actions are necessary in the existing National HIV Programme.
PMID- 28695081
TI - Going door-to-door to reach men and young people with HIV testing services to
achieve the 90-90-90 treatment targets.
AB - Setting: Mulanje District, Malawi. Objective: To examine the effectiveness of
door-to-door (DtD) testing in reaching young people and men in a remote, rural
area with a high prevalence of human immunodeficiency virus (HIV) infection.
Design: This was a retrospective analysis of data collected for a pilot DtD
program. HIV testing services (HTS) visited targeted villages for 1-2 weeks. All
current residents aged ?2 years not known to be HIV-positive were offered
testing. Results: Ninety per cent (13 783/15 391) of individuals eligible for
testing accepted. Forty-one per cent (n = 5693) of those tested were males and
56% (n = 7752) were aged <20 years. The overall proportion who tested positive
was 4% (n = 524), with half as many males as females testing positive (OR 0.49,
95%CI 0.40-0.60, P < 0.001). There was a higher positive yield rate for those
aged ?20 years (6% for men and 8% for women). Two thirds were first-time testers;
males were half as likely as females to have been previously tested (OR 0.43,
95%CI 0.40-0.47, P < 0.001). Conclusion: DtD-HTS can be an effective way to reach
populations in remote, rural high-prevalence areas where access to fixed
facilities is inadequate. It has the potential to reach young people and men
better than facility-based testing or other community strategies, and can
identify young HIV-positive children who may have been missed by other methods.
PMID- 28695082
TI - Tuberculosis treatment success among rural and urban Ugandans living with HIV: a
retrospective study.
AB - Setting: Government health centres and hospitals (six urban and 20 rural)
providing tuberculosis (TB) treatment for people living with the human
immunodeficiency virus (PLHIV) in central and western Uganda. Objective: To
identify and quantify modifiable factors that limit TB treatment success among
PLHIV in rural Uganda. Design: A retrospective cross-sectional review of routine
Uganda National Tuberculosis and Leprosy Programme clinic registers and patient
files of HIV-positive patients who received anti-tuberculosis treatment in 2014.
Results: Of 191 rural patients, 66.7% achieved treatment success compared to
81.1% of 213 urban patients. Adjusted analysis revealed higher average treatment
success in urban patients than in rural patients (OR 3.95, 95%CI 2.70-5.78, P <
0.01, generalised estimating equation model). Loss to follow-up was higher and
follow-up sputum smear results were less frequently recorded in TB clinic
registers among rural patients. Patients receiving treatment at higher-level
facilities in rural settings had greater odds of treatment success, while
patients receiving treatment at facilities where drug stock-outs had occurred had
lower odds of treatment success. Conclusion: Lower reported treatment success in
rural settings is mainly attributed to clinic-centred factors such as treatment
monitoring procedures. We recommend strengthening treatment monitoring and
delivery.
PMID- 28695083
TI - Integration of childhood TB into guidelines for the management of acute
malnutrition in high burden countries.
AB - Introduction: Childhood tuberculosis (TB) and undernutrition are major global
public health challenges. In 2015, although an estimated 1 million children aged
<15 years developed TB, the majority of the cases remain undiagnosed, partly due
to a lack of awareness and capacity by providers who serve as the first point of
care for sick children. This calls for better integration of TB with child health
and nutrition services. TB can cause or worsen undernutrition, and undernutrition
increases the risk of TB. Methods: Guidelines for the management of acute
malnutrition from 17 high TB burden countries were reviewed to gather information
on TB symptom screening, exposure history, and treatment. Results: Seven (41%)
countries recommend routine TB screening among children with acute malnutrition,
and six (35%) recommend obtaining a TB exposure history. Conclusion: TB screening
is not consistently included in guidelines for acute malnutrition in high TB
burden countries. Routine TB risk assessment, especially history of TB exposure,
among acutely malnourished children, combined with improved linkages with TB
services, would help increase TB case finding and could impact outcomes.
Operational research on how best to integrate services at different levels of the
health care system is needed.
PMID- 28695084
TI - Unfavourable outcomes among patients with MDR-TB on the standard 24-month regimen
in Maharashtra, India.
AB - Setting: Patients with multidrug-resistant tuberculosis (MDR-TB) registered for
treatment (2011-2012 cohort) using the standard 24-month regimen, under the
Revised National TB Control Programme's programmatic management of drug-resistant
TB (PMDT), Maharashtra, India. Objectives: To assess the treatment outcomes and
the timing and risk factors for unfavourable treatment outcomes, with a focus on
death and loss to follow-up (LTFU). Method: This was a retrospective cohort study
involving a review of PMDT records. Treatment outcomes were reported on 31
December 2014. Results: Of 4024 patients, treatment success was recorded in 1168
(29%). Unfavourable outcomes occurred in 2242 (56%), of whom 857 (21%) died and
768 (19%) were lost to follow-up. Treatment outcomes were missing on record
review for 375 (9%) patients, and 239 (6%) were still undergoing treatment. Half
of LTFU occurred within 3 months, and more than four fifths of deaths occurred
after 6 months of treatment. Human immunodeficiency virus infection, being
underweight, age ? 15 years, male sex and pulmonary TB were the main risk factors
for death, LTFU or other unfavourable treatment outcomes. Conclusion: The study
found poor treatment outcomes in patients with MDR-TB registered for treatment in
Maharashtra, India. Interventions are required to address the high rates of LTFU
and death.
PMID- 28695085
TI - Using mHealth to enhance TB referrals in a tribal district of India.
AB - Background: A mobile health (mHealth) technology based application was developed
to help rural health care providers (RHCPs) identify and refer presumptive
tuberculosis (TB) patients to the nearest microscopy centre for sputum
examination using mobile applications on their smart phones. Objective: To
determine the feasibility and yield of presumptive TB case referrals by RHCPs
using mHealth technology. Methods: The project was implemented in the tribal
population of Khunti District, Jharkhand State, India, from April 2012 to
February 2015. 'ComCare', a mobile application designed as an aid for health care
providers, was introduced and RHCPs were trained in its use. Results: Of 171
RHCPs who were formally trained to identify and refer presumptive TB patients, 30
were trained in the use of the mobile application. There were 35 referrals of
presumptive TB patients per RHCP using the mobile application, and four each by
RHCPs who were not using the application. Of the 194 TB cases diagnosed, RHCPs
using the application contributed 127 (i.e., 4 TB cases per RHCP), while other
RHCPs contributed 67 (0.5 TB case per RHCP). Conclusion: mHealth technology was
highly effective, and increased both public and private health care provider
accountability to patients.
PMID- 28695086
TI - Alarming rates of attrition among tuberculosis patients in public-private
facilities in Lahore, Pakistan.
AB - Setting: All public-private mix (PPM) facilities caring for tuberculosis (TB)
patients in Lahore city, Pakistan, under four models: PPM1 (general
practitioners), PPM2 (non-governmental organisations), PPM3 (private hospitals)
and PPM4 (others). Objective: To assess the pre-treatment loss to follow-up
(LTFU), defined as patients documented in the laboratory registers but not in the
treatment registers of any PPM facility, among sputum smear-positive TB patients
diagnosed during January-March 2015, and unfavourable treatment outcomes among
patients registered for treatment and associated factors. Design: This was a
retrospective cohort study reviewing existing programme records. Poisson
regression was used to identify factors associated with outcomes. Results: Of
2473 patients diagnosed, 1590 (64%) were lost to follow-up before treatment. This
was higher among males (68%) and the elderly (79%), and lower among 'high
positives' (smear grading 2+ or 3+, 53%) and in the PPM1 model (34%). Of 883
patients started on treatment, 165 (19%) had unfavourable outcomes: 8% LTFU, 5%
treatment failure, 3% died and 3% not evaluated. Previously treated patients
(34%) and children (44%) had the worst outcomes. Conclusion: Pre-treatment LTFU
was alarmingly high and requires urgent attention, including the development and
institution of mechanisms for patient tracking using information and mobile phone
technology, and making TB notification mandatory in the private sector.
PMID- 28695087
TI - Tuberculosis treatment outcomes among disadvantaged patients in India.
AB - Setting: Urban slums and poor rural areas in India, 2012-2014. Objective: To
describe the characteristics of tuberculosis (TB) patients enrolled in treatment
through Operation ASHA, a non-governmental organisation serving disadvantaged
populations in India, and to identify risk factors for unfavourable treatment
outcomes. Design: This was a retrospective cohort study. Patient characteristics
were assessed for their relationship with treatment outcomes using mixed effects
logistic regression, adjusting for clustering by treatment centre and Indian
state. Outcomes were considered favourable (cured/treatment completed) or
unfavourable (treatment failure, loss to follow-up, death, switch to multidrug
resistant TB treatment, transfer out). Results: Of 8415 patients, 7148 (84.9%)
had a favourable outcome. On multivariable analysis, unfavourable outcomes were
more common among men (OR 1.31, 95%CI 1.15-1.51), older patients (OR 1.12, 95%CI
1.04-1.21) and previously treated patients (OR 2.05, 95%CI 1.79-2.36). Compared
to pulmonary smear-negative patients, those with extra-pulmonary disease were
less likely to have unfavourable outcomes (OR 0.72, 95%CI 0.60-0.87), while smear
positive pulmonary patients were more likely to have unfavourable outcomes (OR
1.38, 95%CI 1.15-1.66 for low [scanty/1+] and OR 1.71, 95%CI 1.44-2.04 for high
[2+/3+] positive smears). Conclusion: The treatment success rate within Operation
ASHA is comparable to that reported nationally for India. Men, older patients,
retreatment cases and smear-positive pulmonary TB patients may need additional
interventions to ensure a favourable outcome.
PMID- 28695088
TI - Gastric specimens for diagnosing tuberculosis in adults unable to expectorate in
Rawalpindi, Pakistan.
AB - Setting: Adult pulmonary tuberculosis (TB) patients unable to expectorate quality
sputum represent a diagnostic challenge. A private hospital in Pakistan routinely
performs gastric aspiration in adults with difficulties expectorating. Objective:
To assess the usefulness of gastric specimens (GS) in diagnosing pulmonary TB
(PTB) and drug-resistant TB in adult presumptive TB patients unable to
expectorate, and to compare the diagnostic yield and sensitivity of smear,
culture and the Xpert(r) MTB/RIF assay. Design: This was a comparative cross
sectional study based on retrospective record review. Results: Of 900, 885 and
877 GS tested by smear, Xpert and culture, respectively, interpretable results
were obtained for respectively 900 (100%), 859 (97.1%) and 754 (86.0%), with a
diagnostic yield of respectively 23.6%, 30.3% and 24.9%. The yield was
significantly higher for Xpert in previously treated patients. There were 313
patients with definite TB, defined as positive on Xpert and/or culture. The 82.8%
sensitivity of Xpert was significantly higher than that of smear (61.0%) and
culture (67.8%). Conclusion: GS obtained by aspiration under routine programme
conditions is useful for detecting TB and drug-resistant TB in adult patients
unable to expectorate. Xpert, with its rapid testing, high proportion of
interpretable results and better sensitivity, can substantially improve the
diagnosis of bacteriologically confirmed TB and rifampicin resistance.
PMID- 28695089
TI - Diabetes and pre-diabetes in tuberculosis patients in western Kenya using point
of-care glycated haemoglobin.
AB - Setting: The tuberculosis (TB) clinics of five health facilities in western
Kenya. Objective: To assess the prevalence and associated determinants of
diabetes mellitus (DM) and pre-diabetes hyperglycaemia among adult TB patients
using point-of-care DCA Vantage glycated haemoglobin (HbA1c) devices. Design:
This was a cross-sectional study. Results: Of 454 patients, 272 (60%) were males,
the median age was 34 years, 175 (39%) were co-infected with the human
immunodeficiency virus (HIV), and the median duration of anti-tuberculosis
treatment was 8 weeks; 180 (40%) patients reported at least one classical symptom
suggestive of DM. The prevalence of DM (HbA1c ?6.5%) was 5.1% (95%CI 3.2-7.5),
while that of pre-diabetes (HbA1c 5.7-6.4%) was 37.5% (95%CI 33.1-42.2). The
number needed to screen (NNS) was 19.6 for DM and 2.7 for pre-diabetes. Combined,
42.6% (95%CI 38.0-47.3) of the patients had either pre-diabetes or DM (NNS 2.3).
Seven of the 23 patients with DM knew their prior DM status. Higher rates of DM
were associated with age ?40 years and a family history of DM, but not obesity,
type of TB, HIV status or suggestive symptoms. Conclusions: High rates of pre
diabetes and DM were found in adult TB patients. This study supports the need for
routine screening of all patients with TB for DM in Kenya.
PMID- 28695090
TI - Enrolment and retention of people who inject drugs in the Needle & Syringe
Exchange Programme in Malaysia.
AB - Setting: Needle and Syringe Exchange Programme (NSEP) implemented by non
governmental organisations in Malaysia. Objectives: To determine enrolment,
characteristics and retention in the NSEP of people who inject drugs (PWID)
between 2013 and 2015. Design: Retrospective cohort study. Results: There were 20
946 PWID, with a mean age of 38 years. The majority were male (98%) and of Malay
ethnicity (92%). Follow-up data were available for 20 761 PWID. Annual retention
of newly enrolled PWID for each year was respectively 85%, 87% and 78% for 2013,
2014 and 2015, although annual enrolment over these years declined from 10 724 to
6288 to 3749. Total person-years (py) of follow-up were 27 806, with loss to
follow-up of 40 per 100 py. Cumulative probability of retention in NSEP was 66%
at 12 months, 45% at 24 months and 26% at 36 months. Significantly higher loss to
follow-up rates were observed in those aged 15-24 years or ?50 years, females,
transgender people and non-Malay ethnic groups. Conclusion: Annual retention of
new PWID on NSEP was impressive, although enrolment declined over the 3 years of
the study and cumulative loss to follow-up was high. A better understanding of
these programmatic outcomes is required.
PMID- 28695091
TI - Influence of the 2014-2015 Ebola outbreak on the vaccination of children in a
rural district of Guinea.
AB - Setting: All health centres in Macenta District, rural Guinea. Objective: To
compare stock-outs of vaccines, vaccine stock cards and the administration of
various childhood vaccines across the pre-Ebola, Ebola and post-Ebola virus
disease periods. Design: This was an ecological study. Results: Similar levels of
stock-outs were observed for all vaccines (bacille Calmette-Guerin [BCG],
pentavalent, polio, measles, yellow fever) in the pre-Ebola and Ebola periods
(respectively 2760 and 2706 facility days of stock-outs), with some variation by
vaccine. Post-Ebola, there was a 65-fold reduction in stock-outs compared to pre
Ebola. Overall, 24 facility-months of vaccine stock card stock-outs were observed
during the pre-Ebola period, which increased to 65 facility-months of stock-outs
during the Ebola outbreak period; no such stock-out occurred in the post-Ebola
period. Apart from yellow fever and measles, vaccine administration declined
universally during the peak outbreak period (August-November 2014). Complete
cessation of vaccine administration for BCG and a prominent low for polio (86%
decrease) were observed in April 2014, corresponding to vaccine stock-outs. Post
Ebola, overall vaccine administration did not recover to pre-Ebola levels, with
the highest gaps seen in polio and pentavalent vaccines, which had shortages of
respectively 40% and 38%. Conclusion: These findings highlight the need to
sustain vaccination activities in Guinea so that they remain resilient and
responsive, irrespective of disease outbreaks.
PMID- 28695092
TI - Where technology does not go: specialised neonatal care in resource-poor and
conflict-affected contexts.
AB - Setting: Although neonatal mortality is gradually decreasing worldwide, 98% of
neonatal deaths occur in low- and middle-income countries, where hospital care
for sick and premature neonates is often unavailable. Medecins Sans Frontieres
Operational Centre Brussels (MSF-OCB) managed eight specialised neonatal care
units (SNCUs) at district level in low-resource and conflict-affected settings in
seven countries. Objective: To assess the performance of the MSF SNCU model
across different settings in Africa and Southern Asia, and to describe the set-up
of eight SNCUs, neonate characteristics and clinical outcomes among neonates from
2012 to 2015. Design: Multicentric descriptive study. Results: The MSF SNCU model
was characterised by an absence of high-tech equipment and an emphasis on
dedicated nursing and medical care. Focus was on the management of hypothermia,
hypoglycaemia, feeding support and early identification/treatment of infection.
Overall, 11 970 neonates were admitted, 41% of whom had low birthweight (<2500
g). The main diagnoses were low birthweight, asphyxia and neonatal infections.
Overall mortality was 17%, with consistency across the sites. Chances of survival
increased with higher birthweight. Conclusion: The standardised SNCU model was
implemented across different contexts and showed in-patient outcomes within
acceptable limits. Low-tech medical care for sick and premature neonates can and
should be implemented at district hospital level in low-resource settings.
PMID- 28695093
TI - Operational implementation and impact of The Union's online childhood TB training
course in South Africa.
AB - Novel, effective tuberculosis (TB) training strategies are needed in developing
settings to scale up training and improve TB management at facility level. This
study evaluated the feasibility of implementing an online childhood TB training
course for community-based health-care workers in the Eastern Cape Province,
South Africa, and measured its impact on knowledge. Training sessions were
convened and participants completed the course independently. A total of 220
primary care participants completed pre- and post-training tests. The mean
knowledge increase was 8% (95% confidence interval 7.0-8.8, P < 0.001). The
course proved an acceptable, versatile option for decentralised training in
childhood TB, provided that the technology requirements can be met.
PMID- 28695094
TI - Measuring the performance of active TB case finding: programme managers need to
be cautious.
PMID- 28695095
TI - How we ensured 100% TB notification: experiences from a private tertiary care
hospital in India.
PMID- 28695096
TI - Standards of health promoting hospitals: 68 or 40 measurable elements?
PMID- 28695097
TI - Physiotherapy in Indian communities: a brief review.
AB - Background: Importance of community rehabilitation in India has been emphasized
in previous research. There is ample research that has been published for
different communities in the country. However, the precise role of physiotherapy
in community rehabilitation is unclear.The objective of the current brief report
is to look into the role of physiotherapy in community rehabilitation. Methods:
Relevant literature search was done using databases namely Medline, Scopus,
PubMed, PEDro and CINAHL using search terms- India, community rehabilitation,
home rehabilitation, home exercises and physiotherapy. Studies that followed the
PICO format, published in English,after 2005 and that had specifically mentioned
the role of physiotherapy in community projects were included. Results: While
there are handful of studies that have mentioned the contribution of
physiotherapy in the community, most of the interventions are targeted toward
management of chronic health conditions. More work needs to be done to outline
the importance and precise role of physiotherapy in the rehabilitation of
communities in India, especially in preventive care.A model has been created to
emphasize the holistic approach of physiotherapy in the Indian setting.
Conclusion: Physiotherapy has a pivotal position in community rehabilitation in
India.However, published research for the same is lacking. While physiotherapy
interventions have been designed to target chronic health conditions in the
community, emphasis on preventive care is lacking.
PMID- 28695098
TI - A systematic review of the research evidence on cross-country features of illegal
abortions.
AB - Background: There are contrasting debates about abortions and prohibitory
regulations posed serious public health challenges especially in underdeveloped
and developing countries. Due to paucity of the empirical evidences this study
was conducted to explore the existent cumulative knowledge with special focus on
the applied methodology. Methods: A comprehensive review of published articles
from January 1995 to December 2015 was performed. Several databases including:
Embase, PubMed, Cochrane and also databasesof the Iranian medical journals were
searched using combinations of relevant Medical Subject Headings (MeSH terms) and
their equivalents, i.e., induced abortion, embryotomy, criminal abortion and
illegal abortion. The STrengthening the Reporting of OBservational studies in
Epidemiology (STROBE) statement for appraisal of the cross-sectional studies and
Consolidated Criteria for Reporting Qualitative Research (COREQ) checklist for
the qualitative reports were utilized. After removal of duplicates and irrelevant
publications 36 articles remained for data analysis. Results: A wide
heterogeneity was observed in the utilized methodology with no standard data
collection tool. Face to face interview and self-administered questionnaire were
the most common reported data collection/tool respectively. Married and
unemployed women of 26-30 years old age group with low socioeconomic backgrounds
were the most typical illegal abortees in the included studies. Conclusion:
Despite limitation in accessing all relevant publications and including only
those reports written in English or Persian languages, the accumulated knowledge
might be applicable to develop a potentially inclusive data collection tool and
hence, improve the quality of data collection and/or application of a more robust
study design in future investigations.
PMID- 28695099
TI - Psycho-Socioeconomic bio-behavioral influences on health-related quality of life.
AB - Background: The cumulative effects of psychological, socioeconomic, biological
and behavioral parameters on health-related quality of life (HRQOL) has not been
thoroughly evaluated, which was this study's purpose. Methods: Data from the 2005
2006 National Health and Nutrition Examination Survey were used (N = 2524 adults
20-85 years). HRQOL assessed from the Centers for Disease Control and Prevention
HRQOL survey, with a higher score indicating worse HRQOL. Evaluated parameters
included psychological function, socioeconomic risk, biological function and
behavioral parameters. Ultimately, 14 psycho-socioeconomic bio-behavioral (PSBB)
parameters were evaluated. Results: For every 1 unit increase in the PSBB index,
participants had a corresponding -0.35 lower HRQOL score (beta =-0.35; 95% CI:
0.44, -0.25; P<0.001). All individual components of PSBB were inversely
associated with PSBB. Conclusion: PSBB was both individually and cumulatively
associated with HRQOL.
PMID- 28695100
TI - Tobacco use related attitudes and behaviors in Indian Adolescents: association
with school-based prevention education.
AB - Background: Adolescent tobacco use in India has increased substantially within
the past few decades. Schools can serve as an important avenue for prevention
education, but little is known about the current practices of Indian schools in
relation to tobacco use prevention education. Methods: To assess the extent and
influence tobacco use prevention education in Indian schools,we analyzed the
Global Youth Tobacco Survey data for India, which was a population-based study of
a national random sample of 10112 students from 180 private and public
schools.Variables such as student demographic profile, tobacco use behavior,
perceptions about tobacco use, and exposure to school-based tobacco use
prevention education were considered for analyses. Results: Prevalence of any
form of tobacco use (14%) and current smoking (8%) was found to differ by gender.
A quarter of the students believed that boys who smoke are more attractive or
have more friends compared to non-smokers, and almost half of the students
reported that smoking and health were never discussed as a part of a lesson in
school. The association between school-based prevention education and tobacco use
behavior was assessed (after adjustment forage, gender, and parental smoking).
Students who were educated in school about tobacco use and its effects were
significantly more likely to have negative attitude toward tobacco use and less
likely to report use of tobacco. Conclusion: School-based tobacco use prevention
education has beneficial influence on adolescents in India. Given the early age
of initiation of tobacco use, school curricula in India should emphasize on
tobacco use prevention education.
PMID- 28695101
TI - Assessing the active living environment in three rural towns with a high
proportion of Native Hawaiians and other Pacific Islanders.
AB - Background: Existing literature on the built environment and physical activity in
rural areas is very limited. Studies have shown that residents in rural areas are
less likely to meet physical activity requirements than their counterparts living
in urban and suburban areas. They are also less likely to have access to
amenities and programs that promote physical activity. This study seeks to fill
gaps in the literature by assessing the built environment in three rural towns in
Hawai'i that have a high proportion of Native Hawaiians and other Pacific
Islanders. Methods: The Rural Active Living Assessment (RALA) tools will be used
to assess the built environment. The RALA has three components - Policy and
Program Assessment (PPA), Town Wide Assessment (TWA), and Street Segment
Assessment (SSA) which will be used to provide a comprehensive assessment of the
active living environment. Assessments were completed in September and October
2016. Results: One assessment was completed in each town for the TWA and PPA. The
SSA was completed with 60 segments (20 from each town). Conclusion: The RALA
tools identified supports in these three rural towns. The assessment also
identified barriers and gaps - especially with the town and school polices of
each town.
PMID- 28695102
TI - How young pedestrians do explain their risky road crossing behaviors? A
qualitative study in Iran.
AB - Background: Although pedestrian-vehicle accidents are often the results of risky
behaviors during road crossings, there is limited evidence concerning the risky
road crossing behaviors of pedestrians. This study was aimed at eliciting and
exploring the reasons that can help explain why young pedestrians take risky road
crossing behaviors. Methods: A qualitative content analysis approach was
conducted on purposefully selected young individuals who had the experience of
vehicle-collision accident. Data collected by in depth, semi-structured
interviews until data saturation and concurrently analyzed, assisted by MAXQDA
10. Results: Three main categories emerged as social reasons for risky road
crossing behaviors of the young pedestrians including 'conformity with the
masses/crowds', 'lack of social cohesion and sense of belonging in social
relations' and 'bypassing the law/ law evasion'. Conclusion: The risky road
crossing behaviors of young pedestrians are found influenced by the pedestrian
attitudes towards the political, social, cultural and economic condition of the
society.Moreover, popular culture and collective behaviors in crossing the roads
influenced the risky behaviors. Hence, personal, cultural and social
interventions could be effective in promoting the young pedestrians' behavior.
PMID- 28695103
TI - Reports on boys', youth's and men's health in Canadian newspapers: Now what?
AB - Background: This media content analysis explored the Canadian newspapers
reporting on men's health, and their contribution to public understanding of the
social determinants of men's health and lifestyles. Methods: A media content
analysis of 44 news articles on boys', youth's and men's health,published from
2010 to 2014 by three national newspapers (The Globe and Mail, National Post,and
Metro News). Results: Data indicated that the predominant discourse consists of
informative and awareness messages, mostly about men's prostate and sexual
health. Very little health news content referred to working conditions, education
and income, all of which are significant social determinants of health (SDH).
This may reflect the current state of health research, which does not adequately
incorporate the effects of these determinants. It may also indicate a
reproduction of dominant health knowledge and understanding of masculinity.
Little content was found on policy solutions to other publicized health issues,
such as limited access to health services or inter-sectoral collaborations; this
reflects a lack of government action and a lack of citizen engagement toward the
creation of a concerted men's health policy. Conclusion: Despite the acknowledged
importance of the media in promoting access to health information and indirectly
contributing to improve the general public's level of health literacy, it is also
necessary to remember that there must be a greater attention to the structural
constraints imposed by socioeconomic inequalities. Future studies should explore
media discourses about men's unequal access to health care services and citizens'
awareness of ways to overcome those inequalities shortcomings.
PMID- 28695104
TI - Total diet, individual meals, and their association with gastroesophageal reflux
disease.
AB - Background: To identify the association of total diet and individual meals with
gastroesophageal reflux disease (GERD). Methods: This age- and sex-matched case
control study was carried out among 217 subjects (106 cases and 111 controls).
Data were collected using a demographic questionnaire and a GERD checklist and a
3-day food record. Results: Cases consumed more fat (median: 26.3 [3.2-71.5] g
vs. 21.8 [4.3-58.1] g; P=0.04)and more energy percent form carbohydrates (median:
72.5 [0-100] vs. 69.0 [0-100]; P=0.02)at lunch, and less energy (median: 129.5
kcal [0-617.6] vs. 170.5 kcal [0-615.7]; P=0.01) and protein (2.4 [0-19.4] g vs.
3.1 [0-21.8] g; P=0.01) at evening snack, compared to controls.The volume of food
was significantly different between the two group only at lunch (median:516 [161
1292] g vs. 468 [198-1060] g; P=0.02). The percentage of energy from total
dietary protein showed a significant association with GERD after adjusting for
confounders (odds ratio[OR]=0.89; 95% CI: 0.81-0.98). Regarding the individual
meals, amount of fat consumed at lunch (OR=1.02; 95% CI: 1.00-1.05), and amount
of protein intake at evening snack (OR=0.92;95% CI: 0.85-1.00) were significantly
associated with GERD. Meanwhile, caloric density and meal frequency did not
differ significantly between the two groups. Conclusion: Amount of fat consumed
at lunch is positively associated with GERD, whereas the percentage of energy
from total protein and amount of protein intake at evening snack are more likely
to be inversely associated with GERD.
PMID- 28695105
TI - Alcohol and violence in 2017 National Football League Super Bowl commercials.
AB - Background: The National Football League (NFL) Super Bowl is a widely-viewed
sports event and the commercials are especially popular among viewers. Previous
research has demonstrated risky health behaviors in advertisements aired during
sporting events. The purpose of this study was to analyze the content of the
advertisements aired during the 2017 NFL Super Bowl. Methods: This cross
sectional study involved examining the content of all commercials, with an
emphasis on health-compromising behaviors. The themes and highlights of the
advertisements were analyzed based on whether there was a reference to alcohol or
violence. Results: A total of 103 unique commercials were analyzed. The most
common themes were humor (n=43), happiness (n=25), innovation (n=25), and
enjoyment or relaxation (n=25).Alcohol was referenced in 13 (12.6%, 95% CI 7.5%,
20.4%) of the commercials. Advertisements with alcohol references were more
likely to contain the themes of partying (odds ratio [OR]:16.2, 95% CI 1.4-193.4,
P=0.041) and enjoyment or relaxation (OR: 4.7, 95% CI 1.4-15.6,P=0.014). There
were 24 commercials with references to violence and these were more likely tobe
promoting a movie (OR: 5.4, 95% CI 3.5-8.2, P<0.001) or television program (OR:
8.9,95% CI 2.6-30.26, P<0.001). Conclusion: Parents should consider whether it is
appropriate for their children to watch a concentrated number of intense images
containing references to alcohol and violence during this popular sporting event.
PMID- 28695106
TI - Quality of healthcare services and its relationship with patient safety culture
and nurse-physician professional communication.
AB - Background: This study investigated quality of healthcare services from patients'
perspectives and its relationship with patient safety culture and nurse-physician
professional communication. Methods: A cross-sectional study was conducted among
300 surgery patients and 101 nurses caring them in a public hospital in Tabriz
Iran. Data were collected using the service quality measurement scale (SERVQUAL),
hospital survey on patient safety culture (HSOPSC) and nurse physician
professional communication questionnaire. Results: The highest and lowest mean
(+/-SD) scores of the patients' perception on the healthcare services quality
belonged to the assurance 13.92 (+/-3.55) and empathy 6.78 (+/-1.88)
domains,respectively. With regard to the patient safety culture, the mean
percentage of positive answers ranged from 45.87% for "non-punitive response to
errors" to 68.21% for "organizational continuous learning" domains. The highest
and lowest mean (+/-SD) scores for the nurse physician professional communication
were obtained for "cooperation" 3.44 (+/-0.35) and "non-participative decision
making" 2.84 (+/-0.34) domains, respectively. The "frequency of reported errors
by healthcare professionals" (B=-4.20, 95% CI = -7.14 to -1.27, P<0.01) and
"respect and sharing of information" (B=7.69, 95% CI=4.01 to 11.36, P<0.001)
predicted the patients'perceptions of the quality of healthcare services.
Conclusion: Organizational culture in dealing with medical error should be
changed to non-punitive response. Change in safety culture towards reporting of
errors, effective communication and teamwork between healthcare professionals are
recommended.
PMID- 28695107
TI - Less sitting, more physical activity and higher cardiorespiratory fitness:
associations with weight status among a national sample of children.
AB - Background: Very few studies have evaluated the independent and combined
associations of sedentary behavior (SB), moderate-to-vigorous physical activity
(MVPA) and cardiorespiratory fitness (CRF) on obesity. Our recent work has
evaluated this paradigm in the adult population,but no study has evaluated this
paradigm in the child population, which was the purpose of this study. Methods: A
national sample of children (N=680, 6-11 years) were evaluated via the National
Youth Fitness Survey; this study was conducted in 2012, employing a nationally
representative sample, occurring across 15 different geographic regions in the
United States. SB and MVPA were assessed via parental recall, with CRF
objectively measured via a treadmill-based aerobic test. Obesity was determined
for measured body mass index. A PACS (Physical Activity Cardiorespiratory
Sedentary) score was created ranging from 0-3, indicating each child's number of
positive characteristics (PA, CRF, SB). Results: Meeting MVPA guidelines (OR
adjusted=0.47; 95% CI: 0.29-0.77) and above-median CRF (OR adjusted=0.12; 95% CI:
0.07-0.21), but not SB (OR adjusted=0.62; 95% CI: 0.35-1.10),were associated with
reduced odds of obesity. Compared to those with a PACS score of 0, the odds of
obesity for PACS scores of 1-3, respectively, were: 0.31 (0.18-0.53), 0.12 (0.04
0.34), and 0.05 (0.02-0.10). Conclusion: These findings highlight the need for
public health strategies to promote child MVPA and CRF, and to reduce SB.
PMID- 28695108
TI - Enhancing the Oncolytic Activity of CD133-Targeted Measles Virus: Receptor
Extension or Chimerism with Vesicular Stomatitis Virus Are Most Effective.
AB - Therapy resistance and tumor recurrence are often linked to a small refractory
and highly tumorigenic subpopulation of neoplastic cells, known as cancer stem
cells (CSCs). A putative marker of CSCs is CD133 (prominin-1). We have previously
described a CD133-targeted oncolytic measles virus (MV-CD133) as a promising
approach to specifically eliminate CD133-positive tumor cells. Selectivity was
introduced at the level of cell entry by an engineered MV hemagglutinin (H). The
H protein was blinded for its native receptors and displayed a CD133-specific
single-chain antibody fragment (scFv) as targeting domain. Interestingly, MV
CD133 was more active in killing CD133-positive tumors than the unmodified MV-NSe
despite being highly selective for its target cells. To further enhance the
antitumoral activity of MV-CD133, we here pursued arming technologies, receptor
extension, and chimeras between MV-CD133 and vesicular stomatitis virus (VSV).
All newly generated viruses including VSV-CD133 were highly selective in
eliminating CD133-positive cells. MV-CD46/CD133 killed in addition CD133-negative
cells being positive for the MV receptors. In an orthotopic glioma model, MV
CD46/CD133 and MVSCD-CD133, which encodes the super cytosine deaminase, were most
effective. Notably, VSV-CD133 caused fatal neurotoxicity in this tumor model. Use
of CD133 as receptor could be excluded as being causative. In a subcutaneous
tumor model of hepatocellular cancer, VSV-CD133 revealed the most potent
oncolytic activity and also significantly prolonged survival of the mice when
injected intravenously. Compared to MV-CD133, VSV-CD133 infected a more than 104
fold larger area of the tumor within the same time period. Our data not only
suggest new concepts and approaches toward enhancing the oncolytic activity of
CD133-targeted oncolytic viruses but also raise awareness about careful toxicity
testing of novel virus types.
PMID- 28695109
TI - Soft-Tissue Sarcoma following Traumatic Injury: Case Report and Review of the
Literature.
AB - Soft-tissue sarcomas (STSs) are a heterogeneous group of tumors, which accounts
for 1-2% of adult cancers worldwide. Despite quite a few reports on traumatic
events followed by STS formation, the link between the two events remains a point
of controversy. In this paper, we present the case of a young patient who had a
rhabdomyosarcoma in the lower extremity, which had developed in the same location
where the patient was wounded by a gunshot 9 years earlier. X-ray and CT scans
clearly showed metal fragments in the area of sarcoma formation. The patient
underwent neoadjuvant chemotherapy treatment, to which the tumor was,
unfortunately, unresponsive. Therefore, the patient was referred to below-knee
amputation of the injured leg. There are several possible etiological factors for
sarcoma development in this patient, including tissue damage and inflammation, as
well as the presence of metal fragments in the tissue and the limb's exposure to
radiation during multiple imaging tests. Here, we will discuss the potential
influence wielded by the injury itself, as well as its complications and its
medical management on the formation of the sarcoma, in light of the current
literature.
PMID- 28695110
TI - Ror2 Signaling and Its Relevance in Breast Cancer Progression.
AB - Breast cancer is a heterogeneous disease and has been classified into five
molecular subtypes based on gene expression profiles. Signaling processes linked
to different breast cancer molecular subtypes and different clinical outcomes are
still poorly understood. Aberrant regulation of Wnt signaling has been implicated
in breast cancer progression. In particular Ror1/2 receptors and several other
members of the non-canonical Wnt signaling pathway were associated with
aggressive breast cancer behavior. However, Wnt signals are mediated via multiple
complex pathways, and it is clinically important to determine which particular
Wnt cascades, including their domains and targets, are deregulated in poor
prognosis breast cancer. To investigate activation and outcome of the Ror2
dependent non-canonical Wnt signaling pathway, we overexpressed the Ror2 receptor
in MCF-7 and MDA-MB231 breast cancer cells, stimulated the cells with its ligand
Wnt5a, and we knocked-down Ror1 in MDA-MB231 cells. We measured the invasive
capacity of perturbed cells to assess phenotypic changes, and mRNA was profiled
to quantify gene expression changes. Differentially expressed genes were
integrated into a literature-based non-canonical Wnt signaling network. The
results were further used in the analysis of an independent dataset of breast
cancer patients with metastasis-free survival annotation. Overexpression of the
Ror2 receptor, stimulation with Wnt5a, as well as the combination of both
perturbations enhanced invasiveness of MCF-7 cells. The expression-responsive
targets of Ror2 overexpression in MCF-7 induced a Ror2/Wnt module of the non
canonical Wnt signaling pathway. These targets alter regulation of other pathways
involved in cell remodeling processing and cell metabolism. Furthermore, the
genes of the Ror2/Wnt module were assessed as a gene signature in patient gene
expression data and showed an association with clinical outcome. In summary,
results of this study indicate a role of a newly defined Ror2/Wnt module in
breast cancer progression and present a link between Ror2 expression and
increased cell invasiveness.
PMID- 28695111
TI - Modulation of the Intratumoral Immune Landscape by Oncolytic Herpes Simplex Virus
Virotherapy.
AB - Vaccines and immunotherapeutic approaches to cancers with the advent of immune
checkpoint inhibitors and chimeric antigen receptor-modified T cells have
recently demonstrated preclinical success and entered clinical trials. Despite
advances in these approaches and combinatorial therapeutic regimens, depending on
the nature of the cancer and the immune and metabolic landscape within the tumor
microenvironment, current immunotherapeutic modalities remain inadequate. Recent
clinical trials have demonstrated clear evidence of significant, and sometimes
dramatic, antitumor activity, and long-term survival effects of a variety of
oncolytic viruses (OVs), particularly oncolytic herpes simplex virus (oHSV).
Acting as a multifaceted gene therapy vector and potential adjuvant-like
regimens, oHSV can carry genes encoding immunostimulatory molecules in its
genome. The oncolytic effect of oHSV and the inflammatory response that the virus
stimulates provide a one-two punch at attacking tumors. However, mechanisms
underlying oHSV-induced restoration of intratumoral immunosuppression demand
extensive research in order to further improve its therapeutic efficacy. In this
review, we discuss the current OV-based therapy, with a focus on the unique
aspects of oHSV-initiated antiviral and antitumor immune responses, arising from
virus-mediated immunological cell death to intratumoral innate and adaptive
immunity.
PMID- 28695112
TI - The Cording Phenotype of Mycobacterium tuberculosis Induces the Formation of
Extracellular Traps in Human Macrophages.
AB - The causative agent of tuberculosis, Mycobacterium tuberculosis, shares several
characteristics with organisms that produce biofilms during infections. One of
these is the ability to form tight bundles also known as cords. However, little
is known of the physiological relevance of the cording phenotype. In this study,
we investigated whether cord-forming M. tuberculosis induce the formation of
macrophage extracellular traps (METs) in human monocyte-derived macrophages.
Macrophages have previously been shown to produce extracellular traps in response
to various stimuli. We optimized bacterial culturing conditions that favored the
formation of the cord-forming phenotype as verified by scanning electron
microscopy. Microscopy analysis of METs formation during experimental infection
of macrophages with M. tuberculosis revealed that cord-forming M. tuberculosis
induced significantly more METs compared to the non-cording phenotype. Deletion
of early secreted antigenic target-6 which is an important virulence factor of M.
tuberculosis, abrogated the ability of the bacteria to induce METs. The release
of extracellular DNA from host cells during infection may represent a defense
mechanism against pathogens that are difficult to internalize, including cord
forming M. tuberculosis.
PMID- 28695113
TI - A simple technique for repositioning of the mandible by a surgical guide prepared
using a three-dimensional model after segmental mandibulectomy.
AB - BACKGROUND: Mandibular reconstruction is performed after segmental
mandibulectomy, and precise repositioning of the condylar head in the
temporomandibular fossa is essential for maintaining preoperative occlusion.
METHODS: In cases without involvement of soft tissue around the mandibular bone,
the autopolymer resin in a soft state is pressed against the lower border of the
mandible and buccal and lingual sides of the 3D model on the excised side. After
hardening, it is shaved with a carbide bar to make the proximal and distal parts
parallel to the resected surface in order to determine the direction of
mandibular resection. On the other hand, in cases that require resection of soft
tissue around the mandible such as cases of a malignant tumor, right and left
mandibular rami of the 3D model are connected with the autopolymer resin to keep
the preoperative position between proximal and distal segments before surgical
simulation. The device is made to fit the lower border of the anterior mandible
and the posterior border of the mandibular ramus. The device has a U-shaped
handle so that adaptation of the device will not interfere with the soft tissue
to be removed and has holes to be fixed on the mandible with screws. RESULTS: We
successfully performed the planned accurate segmental mandibulectomy and the
precise repositioning of the condylar head by the device. CONCLUSIONS: The
present technique and device that we developed proved to be simple and useful for
restoring the preoperative condylar head positioning in the temporomandibular
fossa and the precise resection of the mandible.
PMID- 28695114
TI - Novel approach to the maxillary sinusitis after sinus graft.
AB - BACKGROUND: Postoperative infection occurs when bone graft material is dislodged
into the maxillary sinus cavity and most of the patients are often uncomfortable
with the drainage and irrigation procedures to eradicate the infection. In this
case report, we share a technique in treating patients with such condition.
MATERIAL AND METHODS: A 47-year-old patient was referred after sinus elevation
using the crestal socket osteotome, bone graft, and implant insertion at a local
clinic. Clinical and radiographic findings confirmed the diagnosis of right
maxillary sinusitis. A surgical and medical treatment regimen was applied.
RESULTS: By using this technique for irrigation, we were able to achieve
successful results, and the patient was satisfied due to less discomfort during
the irrigation process. CONCLUSION: This method is a patient-friendly technique
for sinus irrigation. It is not only limited to sinus grafted patients, but also
maxillary sinusitis patients in any other type of odontogenic infection.
PMID- 28695116
TI - Feasibility of an Autism-Focused Augmented Reality Smartglasses System for Social
Communication and Behavioral Coaching.
AB - BACKGROUND: Autism spectrum disorder (ASD) is a childhood-onset
neurodevelopmental disorder with a rapidly rising prevalence, currently affecting
1 in 68 children, and over 3.5 million people in the United States. Current ASD
interventions are primarily based on in-person behavioral therapies that are both
costly and difficult to access. These interventions aim to address some of the
fundamental deficits that clinically characterize ASD, including deficits in
social communication, and the presence of stereotypies, and other autism-related
behaviors. Current diagnostic and therapeutic approaches seldom rely on
quantitative data measures of symptomatology, severity, or condition trajectory.
METHODS: Given the current situation, we report on the Brain Power System (BPS),
a digital behavioral aid with quantitative data gathering and reporting features.
The BPS includes customized smartglasses, providing targeted personalized
coaching experiences through a family of gamified augmented-reality applications
utilizing artificial intelligence. These applications provide children and adults
with coaching for emotion recognition, face directed gaze, eye contact, and
behavioral self-regulation. This preliminary case report, part of a larger set of
upcoming research reports, explores the feasibility of the BPS to provide
coaching in two boys with clinically diagnosed ASD, aged 8 and 9 years. RESULTS:
The coaching intervention was found to be well tolerated and rated as being both
engaging and fun. Both males could easily use the system, and no technical
problems were noted. During the intervention, caregivers reported improved non
verbal communication, eye contact, and social engagement during the intervention.
Both boys demonstrated decreased symptoms of ASD, as measured by the aberrant
behavior checklist at 24-h post-intervention. Specifically, both cases
demonstrated improvements in irritability, lethargy, stereotypy,
hyperactivity/non-compliance, and inappropriate speech. CONCLUSION: Smartglasses
using augmented reality may have an important future role in helping address the
therapeutic needs of children with ASD. Quantitative data gathering from such
sensor-rich systems may allow for digital phenotyping and the refinement of
social communication constructs of the research domain criteria. This report
provides evidence for the feasibility, usability, and tolerability of one such
specialized smartglasses system.
PMID- 28695117
TI - Editorial: Ureteropelvic Junction Obstruction (UPJO) in Infants.
PMID- 28695118
TI - Mycoplasma hominis and Mycoplasma genitalium in the Vaginal Microbiota and
Persistent High-Risk Human Papillomavirus Infection.
AB - BACKGROUND: Recent studies have suggested that the vaginal microenvironment plays
a role in persistence of high-risk human papillomavirus (hrHPV) infection and
thus cervical carcinogenesis. Furthermore, it has been shown that some
mycoplasmas are efficient methylators and may facilitate carcinogenesis through
methylation of hrHPV and cervical somatic cells. We examined associations between
prevalence and persistence of Mycoplasma spp. in the vaginal microbiota, and
prevalent as well as persistent hrHPV infections. METHODS: We examined 194
Nigerian women who were tested for hrHPV infection using SPF25/LiPA10 and we
identified Mycoplasma genitalium and Mycoplasma hominis in their vaginal
microbiota established by sequencing the V3-V4 hypervariable regions of the 16S
rRNA gene. We defined the prevalence of M. genitalium, M. hominis, and hrHPV
based on positive result of baseline tests, while persistence was defined as
positive results from two consecutive tests. We used exact logistic regression
models to estimate associations between Mycoplasma spp. and hrHPV infections.
RESULTS: The mean (SD) age of the study participants was 38 (8) years, 71% were
HIV positive, 30% M. genitalium positive, 45% M. hominis positive, and 40% hrHPV
positive at baseline. At follow-up, 16% of the women remained positive for M.
genitalium, 30% for M. hominis, and 31% for hrHPV. There was a significant
association between persistent M. hominis and persistent hrHPV (OR 8.78, 95% CI
1.49-51.6, p 0.01). Women who were positive for HIV and had persistent M. hominis
had threefold increase in the odds of having persistent hrHPV infection (OR 3.28,
95% CI 1.31-8.74, p 0.008), compared to women who were negative for both.
CONCLUSION: We found significant association between persistent M. hominis in the
vaginal microbiota and persistent hrHPV in this study, but we could not rule out
reverse causation. Our findings need to be replicated in larger, longitudinal
studies and if confirmed, could have important diagnostic and therapeutic
implications.
PMID- 28695119
TI - Sensitivity Analysis and Accuracy of a CFD-TFM Approach to Bubbling Bed Using
Pressure Drop Fluctuations.
AB - Based upon the two fluid model (TFM) theory, a CFD model was implemented to
investigate a cold multiphase-fluidized bubbling bed reactor. The key variable
used to characterize the fluid dynamic of the experimental system, and compare it
to model predictions, was the time-pressure drop induced by the bubble motion
across the bed. This time signal was then processed to obtain the power spectral
density (PSD) distribution of pressure fluctuations. As an important aspect of
this work, the effect of the sampling time scale on the empirical power spectral
density (PSD) was investigated. A time scale of 40 s was found to be a good
compromise ensuring both simulation performance and numerical validation
consistency. The CFD model was first numerically verified by mesh refinement
process, after what it was used to investigate the sensitivity with regards to
minimum fluidization velocity (as a calibration point for drag law), restitution
coefficient, and solid pressure term while assessing his accuracy in matching the
empirical PSD. The 2D model provided a fair match with the empirical time
averaged pressure drop, the relating fluctuations amplitude, and the signal's
energy computed as integral of the PSD. A 3D version of the TFM was also used and
it improved the match with the empirical PSD in the very first part of the
frequency spectrum.
PMID- 28695120
TI - Rehabilitation after Total Laryngectomy-A Tribute to the Pioneers of Voice
Restoration in the Last Two Centuries.
AB - BACKGROUND: The most severe consequence of laryngectomy for patients is the loss
of their voice. For this reason, voice rehabilitation has been an integral aspect
of treatment after total laryngectomy from the very beginning. A wide variety of
different technical and surgical approaches are available and reflect the
problems associated with the rehabilitation of communication and swallowing after
the removal of the larynx. METHODS: We used Internet search engines and libraries
to conduct a search of the current medical literature and historical sources of
medical information in order to identify and summarize landmark work on this
subject. DISCUSSION: Four types of methods have been used to restore the voices
of patients, i.e., external devices, esophageal speech, internal voice
prostheses, and surgically created tracheo-esophageal fistulas that do not
involve the use of a prosthetic device.
PMID- 28695121
TI - Abundance and Diversity of Hydrogenotrophic Microorganisms in the Infant Gut
before the Weaning Period Assessed by Denaturing Gradient Gel Electrophoresis and
Quantitative PCR.
AB - Delivery mode (natural vs. cesarean) and feeding type (breast vs. formula
feeding) are relevant factors for neonatal gut colonization. Biomolecular methods
have shown that the ecological structure of infant microbiota is more complex
than previously proposed, suggesting a relevant presence of unculturable
bacteria. It has also been postulated that among unculturable bacteria,
hydrogenotrophic populations might play a key role in infant health. Sulfate
reducing bacteria (SRB), acetogens, and methanogenic archaea use hydrogenotrophic
pathways within the human colon. However, to date, few studies have reported
detection of hydrogenotrophic microorganisms in newborns, possibly because of
limitations on available group-specific, culture-independent quantification
procedures. In the present work, we analyzed 16 fecal samples of healthy babies
aged 1-6 months by means of quantitative PCR (qPCR) targeting the 16S rRNA or
metabolic functional genes and by denaturing gradient gel electrophoresis (DGGE).
qPCR data showed quantifiable levels of methanogens, SRB, and acetogens in all
samples, indicating that the relative abundances of these microbial groups were
not affected by delivery mode (natural vs. caesarian). DGGE revealed a high
prevalence of the Blautia genus within the acetogenic bacteria despite strong
interindividual variability. Our preliminary results suggest that
hydrogenotrophic microorganisms, which have been a neglected group to date,
should be included in future ecological and metabolic studies evaluating the
infant intestinal microbiota.
PMID- 28695122
TI - Revisiting Postoperative Vision Loss following Non-Ocular Surgery: A Short Review
of Etiology and Legal Considerations.
AB - Postoperative vision loss (POVL) following non-ocular surgery is a serious
complication where the causes are not fully understood. Studies have identified
several causes of POVL as well as risk factors and prevention strategies. POVL
research is made difficult by the fact that cases are often subject to
malpractice claims, resulting in a lack of public access to case reports. This
literature review was conducted in order to identify legal issues as a major
barrier to studying POVL and address how this affects current knowledge. Informed
consent provides an opportunity to overcome legal challenges by reducing
malpractice litigation through educating the patient on this outcome. Providing
pertinent information regarding POVL during the informed consent process has
potential to reduce malpractice claims and increase available clinical
information.
PMID- 28695123
TI - A Q Method Approach to Evaluating Farmers' Perceptions of Foot-and-Mouth Disease
Vaccination in Vietnam.
AB - This study aims to explore the farmers' perceptions of foot-and-mouth disease
(FMD) vaccination using a reflexive research method called Q methodology. A
structured sample was composed of 46 farmers selected according to gender,
farming experience, level of education, and production type. Statements relevant
to the farmers' perceptions of and attitudes toward FMD vaccination, related to
confidence, logistics, costs, and impacts of vaccination were developed. Results
were analyzed by principal component analysis and factor analysis. The influence
of demographics and characterized variables on the respondent's contribution to
each factor was also tested. Regarding the different beliefs and behavior toward
FMD vaccination, the common perceptions held by Vietnamese cattle and pig farmers
were divided into three discourses named Confidence (24 subjects), Belief (12
subjects), and Challenge (6 subjects). The identified discourses represented
57.3% of the variances. Consensus points were found, such as the feeling of being
more secure after FMD vaccination campaigns; the fact that farmers take
vaccination decisions themselves without being influenced by other stakeholders;
the opinion that FMD vaccination is cheaper than the costs of treating a sick
animal; and that vaccines provided by governmental authorities are of high
quality. Part of the studied population did not consider vaccination to be the
first choice strategy in prevention. This raises the question of how to improve
the active participation of farmers in the FMD vaccine strategy. Taking into
consideration farmers' perceptions can help to implement feasible vaccination
strategies at the local level.
PMID- 28695124
TI - Discovery of MicroRNAs and Their Target Genes Related to Drought in Paulownia
"Yuza 1" by High-Throughput Sequencing.
AB - Understanding the role of miRNAs in regulating the molecular mechanisms
responsive to drought stress was studied in Paulownia "yuza 1." Two small RNA
libraries and two degradome libraries were, respectively, constructed and
sequenced in order to detect miRNAs and their target genes associated with
drought stress. A total of 107 miRNAs and 42 putative target genes were
identified in this study. Among them, 77 miRNAs were differentially expressed
between drought-treated Paulownia "yuza 1" and the control (60 downregulated and
17 upregulated). The predicted target genes were annotated using the GO, KEGG,
and Nr databases. According to the functional classification of the target genes,
Paulownia "yuza 1" may respond to drought stress via plant hormone signal
transduction, photosynthesis, and osmotic adjustment. Furthermore, the expression
levels of seven miRNAs (ptf-miR157b, ptf-miR159b, ptf-miR398a, ptf-miR9726a, ptf
M2153, ptf-M2218, and ptf-M24a) and their corresponding target genes were
validated by quantitative real-time PCR. The results provide relevant information
for understanding the molecular mechanism of Paulownia resistance to drought and
reference data for researching drought resistance of other trees.
PMID- 28695125
TI - Coexpression Analysis of Transcriptome on AIDS and Other Human Disease Pathways
by Canonical Correlation Analysis.
AB - Acquired immune deficiency syndrome is a severe disease in humans caused by human
immunodeficiency virus. Several human genes were characterized as host genetic
factors that impact the processes of AIDS disease. Recent studies on AIDS
patients revealed a series disease is complicating with AIDS. To resolve gene
interaction between AIDS and complicating diseases, a canonical correlation
analysis was used to identify the global correlation between AIDS and other
disease pathway genes expression. The results showed that HLA-B, HLA-A, MH9,
ZNED1, IRF1, TLR8, TSG101, NCOR2, and GML are the key AIDS-restricted genes
highly correlated with other disease pathway genes. Furthermore, pathway genes in
several diseases such as asthma, autoimmune thyroid disease, and malaria were
globally correlated with ARGs. It suggests that these diseases are a high risk in
AIDS patients as complicating diseases.
PMID- 28695126
TI - Automated Detection of Motion Artefacts in MR Imaging Using Decision Forests.
AB - The acquisition of a Magnetic Resonance (MR) scan usually takes longer than
subjects can remain still. Movement of the subject such as bulk patient motion or
respiratory motion degrades the image quality and its diagnostic value by
producing image artefacts like ghosting, blurring, and smearing. This work
focuses on the effect of motion on the reconstructed slices and the detection of
motion artefacts in the reconstruction by using a supervised learning approach
based on random decision forests. Both the effects of bulk patient motion
occurring at various time points in the acquisition on head scans and the effects
of respiratory motion on cardiac scans are studied. Evaluation is performed on
synthetic images where motion artefacts have been introduced by altering the k
space data according to a motion trajectory, using the three common k-space
sampling patterns: Cartesian, radial, and spiral. The results suggest that a
machine learning approach is well capable of learning the characteristics of
motion artefacts and subsequently detecting motion artefacts with a confidence
that depends on the sampling pattern.
PMID- 28695127
TI - Comparative Analysis of Local Control Prediction Using Different Biophysical
Models for Non-Small Cell Lung Cancer Patients Undergoing Stereotactic Body
Radiotherapy.
AB - PURPOSE: The consistency for predicting local control (LC) data using biophysical
models for stereotactic body radiotherapy (SBRT) treatment of lung cancer is
unclear. This study aims to compare the results calculated from different models
using the treatment planning data. MATERIALS AND METHODS: Treatment plans were
designed for 17 patients diagnosed with primary non-small cell lung cancer
(NSCLC) using 5 different fraction schemes. The Martel model, Ohri model, and the
Tai model were used to predict the 2-year LC value. The Gucken model, Santiago
model, and the Tai model were employed to estimate the 3-year LC data. RESULTS:
We found that the employed models resulted in completely different LC prediction
except for the Gucken and the Santiago models which exhibited quite similar 3
year LC data. The predicted 2-year and 3-year LC values in different models were
not only associated with the dose normalization but also associated with the
employed fraction schemes. The greatest difference predicted by different models
was up to 15.0%. CONCLUSIONS: Our results show that different biophysical models
influence the LC prediction and the difference is not only correlated to the dose
normalization but also correlated to the employed fraction schemes.
PMID- 28695128
TI - Coproduction of Research Questions and Research Evidence in Public Health: The
Study to Prevent Teen Drinking Parties.
AB - Community-based participatory research (CBPR) provides a set of principles and
practices intended to foster coproduction of knowledge. However, CBPR often has
shortcomings when applied to population-level policy and practice interventions,
including a focus on single communities and a lack of focus on policy change. At
the same time, community trials focused on policy have shortcomings, including
lack of stakeholder involvement in framing research questions and modest
engagement in study implementation and interpretation and dissemination of
results. We describe an attempt to hybridize CBPR and community trials by
creating a partnership that included a national membership organization, a
coalition advisory board, intervention and delayed intervention communities, and
an academic study team, which collaborated on a study of community strategies to
prevent underage drinking parties. We use qualitative and quantitative data to
critically assess the partnership. Areas where the partnership was effective
included (1) identifying a research question with high public health
significance, (2) enhancing the intervention, and (3) improving research methods.
Challenges included community coalition representatives' greater focus on their
own communities rather than the production of broader scientific knowledge. This
model can be applied in future attempts to narrow the gap between research,
policy, and practice.
PMID- 28695129
TI - Nonsurgical Treatment for Vocal Fold Leukoplakia: An Analysis of 178 Cases.
AB - OBJECTIVE: To assess the effectiveness and identify vocal fold leukoplakia types
appropriate for nonsurgical treatment. METHODS: The vocal fold leukoplakia in 178
patients was divided by gross appearance into three subtypes: flat and smooth,
elevated and smooth, and rough. All patients received nonsurgical treatment
including smoking and drinking cessation, voice rest, omeprazole, and Chinese
medication therapy. The clinical response of three subtypes was assessed after a
6-month follow-up. RESULTS: Vocal fold leukoplakia subtypes included flat and
smooth (n = 66; 37.1%), elevated and smooth (n = 103; 57.9%), and rough (n = 9;
5.0%). The rate of complete response was 80.3%, 66.0%, and 0.0% for the 3 lesion
types, respectively (rough versus flat and smooth, P < 0.001; rough versus
elevated and smooth, P < 0.001, Fisher's exact test). The incidence of carcinoma
in rough leukoplakia was significantly higher than that in smooth leukoplakia
(44.4% versus 2.4%, P = 0.002, Fisher's exact test). Clinical type was the only
significant factor for clinical response of nonsurgical treatment (P = 0.005,
ordinal logistic regression). CONCLUSIONS: The effectiveness of nonsurgical
treatment for smooth vocal fold leukoplakia is better in comparison to rough
vocal fold leukoplakia. Smooth leukoplakia could be managed with nonsurgical
treatment; more aggressive treatments should be considered for rough leukoplakia.
PMID- 28695130
TI - Autologous and Nonautologous Blood Transfusion in Patients with Ruptured Ectopic
Pregnancy and Severe Blood Loss.
AB - BACKGROUND: There are some theoretical concerns for the use of intraoperative
cell salvage (ICS) in patients with ectopic pregnancy. This study aimed to
observe the impact of ICS on the coagulation function and clinical outcomes of
patients with ruptured ectopic pregnancy and severe blood loss. METHODS: This was
a retrospective study of 225 patients with ruptured ectopic pregnancy and severe
blood loss treated at the Third Affiliated Hospital of Guangxi Medical University
between January 2012 and May 2016. Patients were grouped according to ICS (n =
116) and controls (n = 109, allogenic transfusion and no transfusion). RESULTS:
Compared with controls, patients with ICS had shorter hospitalization (P =
0.007), lower requirement for allogenic blood products (P < 0.001), and higher
hemoglobin levels at discharge (P < 0.001). There were no complications/ adverse
reactions. In the ICS group, hemoglobin at discharge (-6.5%, P = 0.002) and
thrombin time (-3.7%, P = 0.002) were decreased 24 h after surgery, while 24 h
APTT was increased (+4.6%, P < 0.001). In the control group, hemoglobin at
discharge (-16.8%, P < 0.001) was decreased after surgery and 24 h APTT was
increased (+2.4%, P = 0.045). At discharge, hemoglobin levels were higher in the
ICS group (P < 0.001). CONCLUSION: ICS was associated with good clinical outcomes
in patients with ruptured ectopic pregnancy and severe blood loss.
PMID- 28695131
TI - PNPLA3 rs1010023 Predisposes Chronic Hepatitis B to Hepatic Steatosis but
Improves Insulin Resistance and Glucose Metabolism.
AB - PNPLA3 polymorphisms serve as the genetic basis of hepatic steatosis in normal
population and lead to dysregulated glucose metabolism. Whether it underlies the
hepatic steatosis and glucose homeostasis in chronic hepatitis B patients remains
uncertain. Here, we investigated the PNPLA3 polymorphisms in biopsy-proven
chronic hepatitis B patients with (CHB+HS group, n = 52) or without hepatic
steatosis (CHB group, n = 47) and non-CHB subjects with (HS group, n = 37) or
without hepatic steatosis (normal group, n = 45). When compared to the TT
genotype, C-allele at PNPLA3 rs1010023 (CC and TC genotypes) conferred higher
risk to hepatic steatosis in chronic hepatitis B patients (odds ratio (OR) =
1.768, 95% confidence interval (CI): 1.027-3.105; P = 0.045) independent of age,
gender, and body mass index. In contrast to their role in hepatic steatosis, CC
and TC genotypes of PNPLA3 rs1010023 were correlated to significant improvement
of homeostasis model assessment index (HOMA-IR) as compared to TT genotype in the
CHB+HS group. Downregulated fasting blood glucose also characterized the CHB+HS
patients with C-allele at PNPLA3 rs1010023 (CC/TC versus TT: 4.81 +/- 0.92 mmol/L
versus 5.86 +/- 2.11 mmol/L, P = 0.02). These findings suggest that PNPLA3
rs1010023 may predispose chronic hepatitis B patients to hepatic steatosis but
protects them from glucose dysregulation by attenuating insulin resistance.
PMID- 28695132
TI - High Serum Advanced Glycation End Products Are Associated with Decreased Insulin
Secretion in Patients with Type 2 Diabetes: A Brief Report.
AB - OBJECTIVE: Advanced glycation end products (AGEs) are important in the
pathophysiology of type 2 diabetes mellitus (T2DM). They directly cause insulin
secretory defects in animal and cell culture models and may promote insulin
resistance in nondiabetic subjects. We have developed a highly sensitive liquid
chromatography-tandem mass spectrometry method for measuring AGEs in human serum.
Here, we use this method to investigate the relationship between AGEs and insulin
secretion and resistance in patients with T2DM. METHODS: Our study involved 15
participants with T2DM not on medication and 20 nondiabetic healthy participants.
We measured the AGE carboxyethyllysine (CEL), carboxymethyllysine (CML), and
methyl-glyoxal-hydro-imidazolone (MG-H1). Plasma glucose and insulin were
measured in these participants during a meal tolerance test, and the glucose
disposal rate was measured during a euglycemic-hyperinsulinemic clamp. RESULTS:
CML and CEL levels were significantly higher in T2DM than non-DM participants.
CML showed a significant negative correlation with insulin secretion, HOMA-%B,
and a significant positive correlation with the insulin sensitivity index in T2DM
participants. There was no correlation between any of the AGEs measured and
glucose disposal rate. CONCLUSIONS: These results suggest that AGE might play a
role in the development or prediction of insulin secretory defects in type 2
diabetes.
PMID- 28695133
TI - Role of Epigenetic Histone Modifications in Diabetic Kidney Disease Involving
Renal Fibrosis.
AB - One of the commonest causes of end-stage renal disease is diabetic kidney disease
(DKD). Renal fibrosis, characterized by the accumulation of extracellular matrix
(ECM) proteins in glomerular basement membranes and the tubulointerstitium, is
the final manifestation of DKD. The TGF-beta pathway triggers epithelial-to
mesenchymal transition (EMT), which plays a key role in the accumulation of ECM
proteins in DKD. DCCT/EDIC studies have shown that DKD often persists and
progresses despite glycemic control in diabetes once DKD sets in due to prior
exposure to hyperglycemia called "metabolic memory." These imply that epigenetic
factors modulate kidney gene expression. There is evidence to suggest that in
diabetes and hyperglycemia, epigenetic histone modifications have a significant
effect in modulating renal fibrotic and ECM gene expression induced by TGF-beta1,
as well as its downstream profibrotic genes. Histone modifications are also
implicated in renal fibrosis through its ability to regulate the EMT process
triggered by TGF-beta signaling. In view of this, efforts are being made to
develop HAT, HDAC, and HMT inhibitors to delay, stop, or even reverse DKD. In
this review, we outline the latest advances that are being made to regulate
histone modifications involved in DKD.
PMID- 28695134
TI - Relationships between Bone Turnover and Energy Metabolism.
AB - It is well established that diabetes can be detrimental to bone health, and its
chronic complications have been associated with an increased risk of osteoporotic
fracture. However, there is growing evidence that the skeleton plays a key role
in a whole-organism approach to physiology. The hypothesis that bone may be
involved in the regulation of physiological functions, such as insulin
sensitivity and energy metabolism, has been suggested. Given the roles of
insulin, adipokines, and osteocalcin in these pathways, the need for a more
integrative conceptual approach to physiology is emphasized. Recent findings
suggest that bone plays an important role in regulating intermediary metabolism,
being possibly both a target of diabetic complications and a potential
pathophysiologic factor in the disease itself. Understanding the relationships
between bone turnover and glucose metabolism is important in order to develop
treatments that might reestablish energy metabolism and bone health. This review
describes new insights relating bone turnover and energy metabolism that have
been reported in the literature.
PMID- 28695135
TI - Immunomodulating and Revascularizing Activity of Kalanchoe pinnata Synergize with
Fungicide Activity of Biogenic Peptide Cecropin P1.
AB - Previously transgenic Kalanchoe pinnata plants producing an antimicrobial peptide
cecropin P1 (CecP1) have been reported. Now we report biological testing K.
pinnata extracts containing CecP1 as a candidate drug for treatment of wounds
infected with Candida albicans. The drug constitutes the whole juice from K.
pinnata leaves (not ethanol extract) sterilized with nanofiltration. A
microbicide activity of CecP1 against an animal fungal pathogen in vivo was
demonstrated for the first time. However, a favorable therapeutic effect of the
transgenic K. pinnata extract was attributed to a synergism between the fungicide
activity of CecP1 and wound healing (antiscar), revascularizing, and
immunomodulating effect of natural biologically active components of K. pinnata.
A commercial fungicide preparation clotrimazole eliminated C. albicans cells
within infected wounds in rats with efficiency comparable to CecP1-enriched K.
pinnata extract. But in contrast to K. pinnata extract, clotrimazole did not
exhibit neither wound healing activity nor remodeling of the scar matrix. Taken
together, our results allow assumption that CecP1-enriched K. pinnata extracts
should be considered as a candidate drug for treatment of dermatomycoses, wounds
infected with fungi, and bedsores.
PMID- 28695136
TI - Range of Hip Joint Motion Is Correlated With MRI-Verified Cam Deformity in
Adolescent Elite Skiers.
AB - BACKGROUND: Radiologically verified cam-type femoroacetabular impingement (FAI)
has been shown to correlate with reduced internal rotation, reduced passive hip
flexion, and a positive anterior impingement test. PURPOSE: To validate how a
clinical examination of the hip joint correlates with magnetic resonance imaging
(MRI)-verified cam deformity in adolescents. STUDY DESIGN: Cross-sectional study;
Level of evidence, 3. METHODS: The sample group consisted of 102 adolescents with
the mean age 17.7 +/- 1.4 years. The hip joints were examined using MRI for
measurements of the presence of cam (alpha-angle >=55 degrees ) and clinically
for range of motion (ROM) in both supine and sitting positions. The participants
were divided into a cam and a noncam group based on the results of the MRI
examination. Passive hip flexion, internal rotation, anterior impingement, and
the FABER (flexion, abduction, and external rotation) test were used to test both
hips in the supine position. With the participant sitting, the internal/external
rotation of the hip joint was measured in 3 different positions of the pelvis
(neutral, maximum anteversion, and retroversion) and lumbar spine (neutral,
maximum extension, and flexion). RESULTS: Differences were found between the cam
and noncam groups in terms of the anterior impingement test (right, P = .010;
left, P = .006), passive supine hip flexion (right: mean, 5 degrees ; cam, 117
degrees ; noncam, 122 degrees [P = .05]; and left: mean, 8.5 degrees ; cam, 116
degrees ; noncam, 124.5 degrees [P = .001]), supine internal rotation (right:
mean, 4.9 degrees ; cam, 24 degrees ; noncam, 29 degrees [P = .022]; and left:
mean, 4.8 degrees ; cam, 26 degrees ; noncam, 31 degrees [P = .028]), sitting
internal rotation with the pelvis and lumbar spine in neutral (right: mean, 7.95
degrees ; cam, 29 degrees ; noncam, 37 degrees [P = .001]; and left: mean, 6.5
degrees ; cam, 31.5 degrees ; noncam, 38 degrees [P = .006]), maximum
anteversion of the pelvis and extension of the lumbar spine (right: mean, 5.2
degrees ; cam, 20 degrees ; noncam, 25 degrees [P = .004]; and left: mean, 5.85
degrees ; cam, 20.5; noncam, 26.4 degrees [P = .004]), and maximum retroversion
of the pelvis and flexion of the spine (right: mean, 8.4 degrees ; cam, 32.5
degrees ; noncam, 41 degrees [P = .001]; and left: mean, 6.2 degrees ; cam, 36
degrees ; noncam, 42.3 degrees [P = .012]). The cam group had reduced ROM
compared with the noncam group in all clinical ROM measures. CONCLUSION: The
presence of cam deformity on MRI correlates with reduced internal rotation in the
supine and sitting positions, passive supine hip flexion, and the impingement
test in adolescents.
PMID- 28695137
TI - Trends in Surgical Management of Shoulder Instability.
AB - BACKGROUND: Optimal surgical management of anterior shoulder instability remains
controversial. There is a need to assess the most recent trends for primary and
revision shoulder stabilization surgery using a national database significantly
larger than those previously utilized. HYPOTHESIS: Most shoulder stabilization
procedures are performed arthroscopically. Examining revision procedures, we
hypothesized that open procedures would result in decreased revision
stabilizations compared with arthroscopic procedures and that most revision
procedures would be open Bankart or bone transfer procedures regardless of the
index procedure technique. STUDY DESIGN: Descriptive epidemiology study. METHODS:
The MarketScan Database was searched using International Classification of
Diseases-Ninth Revision (ICD-9) and Current Procedural Terminology (CPT) codes to
identify patients who underwent any shoulder stabilization procedure between 2008
and 2012. Regression analysis was used to evaluate trends between patient groups.
The Cochran-Armitage trend test was used to identify differences in trends seen
yearly. Odds ratios (ORs) were calculated to compare the likelihood of undergoing
a revision stabilization procedure. RESULTS: A total of 66,564 shoulder
stabilization procedures were identified from 2008 through 2012: 60,248
arthroscopic stabilization procedures (90.5%) and 6316 open stabilization
procedures (9.5%), including 1623 bone block procedures. Arthroscopic
stabilization procedures increased in total number and percentage of all
procedures in each year of the study. Bone block procedures increased in number
each year, although other open procedures decreased during the study period.
Males underwent more stabilization procedures, while patients between the ages of
10 and 19 years were most likely to undergo any procedure. Patients who underwent
bone block stabilization were significantly less likely to undergo a second
stabilization procedure during the study period when compared with open Bankart
repair (OR, 0.582; 95% CI, 0.405-0.836; P < .05) and arthroscopic Bankart repair
(OR, 0.587; 95% CI, 0.418-0.824; P < .05). No statistically significant
difference in revision stabilization was seen when comparing arthroscopic versus
open Bankart repair (OR, 0.934; 95% CI, 0.863-1.139). CONCLUSION: Although the
number of arthroscopic shoulder stabilization surgeries continues to increase,
our data show a consistent increase, not seen in prior studies, in the number of
bone block procedures. Contrary to some studies, there was no significant
difference in the likelihood of a second procedure between patients initially
undergoing arthroscopic compared with open Bankart repair.
PMID- 28695138
TI - Overuse Injuries in Professional Ballet: Influence of Age and Years of
Professional Practice.
AB - BACKGROUND: In spite of the high rate of overuse injuries in ballet dancers, no
studies have investigated the prevalence of overuse injuries in professional
dancers by providing specific diagnoses and details on the differences in the
injuries sustained as a function of age and/or years of professional practice.
HYPOTHESIS: Overuse injuries are the most prevalent injuries in ballet dancers.
Professional ballet dancers suffer different types of injuries depending on their
age and years of professional practice. STUDY DESIGN: Descriptive epidemiology
study. METHODS: This descriptive epidemiological study was carried out between
January 1, 2005, and October 10, 2010, regarding injuries sustained by
professional dancers belonging to the major Spanish ballet companies practicing
classical, neoclassical, contemporary, and Spanish dance. The sample was
distributed into 3 different groups according to age and years of professional
practice. Data were obtained from the specialized medical care the dancers
received from the Trauma and Orthopaedic Surgery Service at Fremap in Madrid. The
dependent variable was the study of the injury. RESULTS: A total of 486 injuries
were identified over the study period, with overuse injuries being the most
common etiology (P < .0001); these injuries were especially prevalent in junior
professional dancers practicing classical ballet and veteran dancers practicing
contemporary ballet (P = .01). Specifically, among other findings, stress
fractures of the base of the second metatarsal (P = .03), patellofemoral
syndrome, and os trigonum syndrome were more prevalent among junior professionals
(P = .04); chondral injury of the knee in senior professionals (P = .04); and
cervical disc disease in dancers of intermediate age and level of experience.
CONCLUSION: Overall, overuse injuries were more prevalent in younger
professionals, especially in women. This finding was especially true for the more
technical ballet disciplines. On the other hand, in the athletic ballet
disciplines, overuse lesions occurred mainly in the more senior professionals.
CLINICAL RELEVANCE: This study provides specific clinical diagnoses obtained
through physical examination as well as details on the different injury types
sustained as a function of age and/or years of professional practice, an
important aspect for ballet and sports practice in general.
PMID- 28695139
TI - Video Analysis of Primary Shoulder Dislocations in Rugby Tackles.
AB - BACKGROUND: Characteristics of rugby tackles that lead to primary anterior
shoulder dislocation remain unclear. PURPOSE: To clarify the characteristics of
tackling that lead to shoulder dislocation and to assess the correlation between
the mechanism of injury and morphological damage of the glenoid. STUDY DESIGN:
Case series; Level of evidence, 4. METHODS: Eleven elite rugby players who
sustained primary anterior shoulder dislocation due to one-on-one tackling
between 2001 and 2014 were included. Using an assessment system, the tackler's
movement, posture, and shoulder and head position were evaluated in each phase of
tackling. Based on 3-dimensional computed tomography, the glenoid of the affected
shoulder was classified into 3 types: intact, erosion, and bone defect.
Orientation of the glenoid defect and presence of Hill-Sachs lesion were also
evaluated. RESULTS: Eleven tackles that led to primary shoulder dislocation were
divided into hand, arm, and shoulder tackle types based on the site at which the
tackler contacted the ball carrier initially. In hand and arm tackles, the
tackler's shoulder joint was forcibly moved to horizontal abduction by the impact
of his upper limb, which appeared to result from an inappropriate approach to the
ball carrier. In shoulder tackles, the tackler's head was lowered and was in
front of the ball carrier at impact. There was no significant correlation between
tackle types and the characteristics of bony lesions of the shoulder. CONCLUSION:
Although the precise mechanism of primary anterior shoulder dislocation could not
be estimated from this single-view analysis, failure of individual tackling
leading to injury is not uniform and can be caused by 2 main factors: failure of
approach followed by an extended arm position or inappropriate posture of the
tackler at impact, such as a lowered head in front of the opponent. These
findings indicate that injury mechanisms should be assessed for each type of
tackle, as it is unknown whether external force to the glenoid is different in
each mechanism during shoulder dislocation.
PMID- 28695140
TI - Changing Body Movement Patterns in 9-Year-Old Baseball Pitchers: A Pilot Study.
AB - BACKGROUND: Arm injuries in throwing athletes continue to increase. Injuries may
be due to multiple variables, including inefficient body movement patterns,
especially in young baseball throwers. It is unclear whether these patterns can
be efficiently altered in this population. PURPOSE/HYPOTHESIS: To investigate the
effect of a novel 21-day throwing program on body movement patterns in youth
baseball players using common practical tools. Our hypothesis was that this
program would change body movement patterns over a relatively short period. STUDY
DESIGN: Descriptive laboratory study. METHODS: Ten 9-year-old baseball athletes
were asked to participate in a 21-consecutive day throwing program focused on
decreasing inefficiencies. All participants underwent video evaluation from 2
vantage points as well as radar evaluation before and after the programs.
Throwing arm humerothoracic and antecubital angles as well as pelvic angles in
the frontal view were measured at the time of front (directional) leg heel/toe
down (late cocking) for each of 3 pitches. Glove-side humerothoracic angles and
back leg minimum popliteal angles were measured from behind for each of 3
additional pitches. Velocity was measured using a radar gun. All angular
measurements were performed by a physical therapist blinded to the purposes of
the program and study as well as to video chronology. RESULTS: Throwing arm
antecubital angle (P = .01) and humerothoracic angle (P = .03) as well as back
leg minimum popliteal angle (P = .03) all decreased, with mean decreases of 35
degrees , 10 degrees , and 8 degrees , respectively. Velocity increased with
decreased back leg popliteal angles (P = .019); mean velocity increased 2.6 mph
(P = .016). CONCLUSION: Young baseball throwers can quickly retrain their bodies
to accomplish different movement patterns. CLINICAL RELEVANCE: This novel
throwing program may have implications for injury prevention and treatment as we
identify better baseball-throwing movement patterns.
PMID- 28695141
TI - Hepatitis B Virus Incidence and Risk Factors Among Human Immunodeficiency Virus-1
Negative Men Who Have Sex With Men in Kenya.
AB - No data exist on hepatitis B virus (HBV) incidence among African men who have sex
with men (MSM). We tested plasma samples archived between 2005 and 2014 for HBV
core antibody or surface antigen seroconversion in a cohort of 312 initially
human immunodeficiency virus (HIV)-1-negative MSM with no evidence of prior HBV
infection. Hepatitis B virus incidence was 6.0/100 person-years (95% confidence
interval [CI], 3.9-9.1). Hepatitis B virus acquisition was associated with being
uncircumcised (adjusted incidence rate ratio [aIRR], 5.0; 95% CI, 1.5-16.8),
recent HIV-1 acquisition (aIRR, 2.9; 95% CI, 1.1-7.7), rape (aIRR, 5.0; 95% CI,
1.2-20.4), and any tertiary education (aIRR, 3.2; 95% CI, 1.1-9.7). African MSM
have a substantial risk of HBV acquisition and require vaccination urgently.
PMID- 28695142
TI - Aspartame Intake Relates to Coronary Plaque Burden and Inflammatory Indices in
Human Immunodeficiency Virus.
AB - BACKGROUND: Dietary sweeteners may contribute to metabolic dysregulation and
cardiovascular disease (CVD), but this has not been assessed in human
immunodeficiency virus (HIV). METHODS: One hundred twenty-four HIV-infected and
56 non-HIV-infected participants, without history of known coronary artery
disease were included. Dietary intake was assessed using a 4-day food record.
Coronary plaque was determined using cardiac computed tomography angiography.
RESULTS: Human immunodeficiency virus-infected participants had significantly
greater intake of dietary sweeteners, including total sugar (P = .03) and added
sugar (P = .009); intake of aspartame (artificial sweetener) was greater among
aspartame consumers with HIV versus non-HIV consumers (P = .03). Among HIV
infected participants, aspartame intake was significantly associated with
coronary plaque (P = .002) and noncalcified plaque (P = .007) segments, as well
as markers of inflammation/immune activation (monocyte chemoattractant protein 1
and lipoprotein-associated phospholipase A2), which may contribute to increased
atherogenesis. In multivariable regression modeling, aspartame remained an
independent predictor of plaque in HIV. In contrast, among non-HIV-infected
participants, no sweetener type was shown to relate to plaque characteristics.
CONCLUSIONS: We demonstrate increased intake of dietary sweeteners and a
potential novel association between aspartame intake, plaque burden, and
inflammation in HIV. Our data suggest that aspartame may contribute to CVD risk
in HIV. Further studies should address potential mechanisms by which aspartame
may contribute to increased plaque burden and cardiovascular benefits of dietary
strategies targeting aspartame intake in HIV.
PMID- 28695143
TI - Lactobacillus rhamnosus Endocarditis After Upper Endoscopy.
AB - Lactobacillus rhamnosus is commonly found in gastrointestinal flora and used in
probiotics but is a rare human pathogen. We report a case of L. rhamnosus
endocarditis following upper endoscopy in a frequent consumer of yogurt
containing the organism, who required aortic and mitral valve replacement for
cure.
PMID- 28695144
TI - Financial Incentives for Adherence to Hepatitis C Virus Clinical Care and
Treatment: A Randomized Trial of Two Strategies.
AB - BACKGROUND: Although rates of sustained virologic response (SVR) after hepatitis
C virus (HCV) treatment with direct-acting antivirals (DAAs) surpass 90% in
trials and some more "real world" settings, some patients, such as those with
substance use disorders, will be challenged to adhere to HCV care. METHODS: To
assess the feasibility of 2 strategies for financially incentivizing adherence to
HCV care, patients with a substance use history prescribed 12 weeks of a
sofosbuvir-containing regimen were randomized to either fixed or lottery-based
monetary incentives for attending clinic appointments, pill count adherence >90%,
and SVR achievement. Electronic medication monitoring provided an objective
measure of DAA adherence. RESULTS: Fifty-nine participants were randomized to the
lottery (n = 31) or fixed-incentive (n = 28) arms. All 31 (100%) in the lottery
arm and 24 of 28 (86%) in the fixed arm completed 12 weeks of therapy. By intent
to-treat, 93% in the lottery arm and 92% in the fixed arm achieved SVR (estimated
difference: 0.5%; 95% confidence interval, -17.5 to 18.8). Overall, 92% of
scheduled visits were attended without significant differences between arms. The
mean adherence ratio (days with >=1 bottle opening:monitored days) was 0.91 for
lottery and 0.92 for fixed arms. CONCLUSIONS: In this pilot, fixed- and lottery
based financial incentives were successfully implemented and accepted by patients
with a substance use history. High levels of HCV therapy and care adherence, as
well as rates of SVR, were observed. Financial incentives may be useful to
support treatment adherence in patients with substance use disorders and should
be tested in a larger, randomized, controlled trial.
PMID- 28695145
TI - Integrated Tuberculosis/Human Immunodeficiency Virus Community-Based Case Finding
in Rural South Africa: Implications for Tuberculosis Control Efforts.
AB - BACKGROUND: Intensive case finding is endorsed for tuberculosis (TB) control in
high-risk populations. Novel case-finding strategies are needed in hard-to-reach
rural populations with high prevalence of TB and human immunodeficiency virus
(HIV). METHODS: We performed community-based integrated HIV and TB intensive case
finding in a rural South African subdistrict from March 2010 to June 2012. We
offered TB symptom screening, sputum collection for microbiologic diagnosis,
rapid fingerstick HIV testing, and phlebotomy for CD4 cell count. We recorded
number of cases detected and calculated population-level rates and number needed
to screen (NNS) for drug-susceptible and -resistant TB. RESULTS: Among 5615
persons screened for TB at 322 community sites, 91.2% accepted concurrent HIV
testing, identifying 510 (9.9%) HIV-positive individuals with median CD4 count of
382 cells/mm3 (interquartile range = 260-552). Tuberculosis symptoms were
reported by 2049 (36.4%), and sputum was provided by 1033 (18.4%). Forty-one
(4.0%) cases of microbiologically confirmed TB were detected for an overall case
notification rate of 730/100000 (NNS = 137); 11 (28.6%) were multidrug-resistant
or extensively drug-resistant TB. Only 5 (12.2%) TB cases were HIV positive
compared with an HIV coinfection rate of 64% among contemporaneously registered
TB cases (P = .001). CONCLUSION: Community-based integrated intensive case
finding is feasible and is high yield for drug-susceptible and -resistant TB and
HIV in rural South Africa. Human immunodeficiency virus-negative tuberculosis
predominated in this community sample, suggesting a distinct TB epidemiology
compared with cases diagnosed in healthcare facilities. Increasing HIV/TB
integrated community-based efforts and other strategies directed at both HIV
positive and HIV-negative tuberculosis may contribute to TB elimination in high
TB/HIV burden regions.
PMID- 28695146
TI - Megalencephalic leukoencephalopathy with cysts: the Glialcam-null mouse model.
AB - OBJECTIVE: Megalencephalic leukoencephalopathy with cysts (MLC) is a genetic
infantile-onset disease characterized by macrocephaly and white matter edema due
to loss of MLC1 function. Recessive mutations in either MLC1 or GLIALCAM cause
the disease. MLC1 is involved in astrocytic volume regulation; GlialCAM ensures
the correct membrane localization of MLC1. Their exact role in brain ion-water
homeostasis is only partly defined. We characterized Glialcam-null mice for
further studies. METHODS: We investigated the consequences of loss of GlialCAM in
Glialcam-null mice and compared GlialCAM developmental expression in mice and
men. RESULTS: Glialcam-null mice had early-onset megalencephaly and increased
brain water content. From 3 weeks, astrocytes were abnormal with swollen
processes abutting blood vessels. Concomitantly, progressive white matter
vacuolization developed due to intramyelinic edema. Glialcam-null astrocytes
showed abolished expression of MLC1, reduced expression of the chloride channel
ClC-2 and increased expression and redistribution of the water channel
aquaporin4. Expression of other MLC1-interacting proteins and the volume
regulated anion channel LRRC8A was unchanged. In mice, GlialCAM expression
increased until 3 weeks and then stabilized. In humans, GlialCAM expression was
highest in the first 3 years to then decrease and stabilize from approximately 5
years. INTERPRETATION: Glialcam-null mice replicate the early stages of the human
disease with early-onset intramyelinic edema. The earliest change is astrocytic
swelling, further substantiating that a defect in astrocytic volume regulation is
the primary cellular defect in MLC. GlialCAM expression affects expression of
MLC1, ClC-2 and aquaporin4, indicating that abnormal interplay between these
proteins is a disease mechanism in megalencephalic leukoencephalopathy with
cysts.
PMID- 28695147
TI - Dysregulation of 14-3-3 proteins in neurodegenerative diseases with Lewy body or
Alzheimer pathology.
AB - OBJECTIVE: The highly conserved 14-3-3 proteins interact with key players
involved in Parkinson's disease (PD) and other neurodegenerative disorders. We
recently demonstrated that 14-3-3 phosphorylation is increased in PD models and
that increased 14-3-3 phosphorylation reduces the neuroprotective effects of 14-3
3 proteins. Here, we investigated whether 14-3-3 phosphorylation is altered in
postmortem brains from control, PD, Alzheimer's Disease (AD), Alzheimer's with
Lewy Bodies (ADLB), Dementia with Lewy Bodies (DLB), and Progressive Supranuclear
Palsy (PSP) subjects at three conserved sites: serine 58 (S58), serine 185
(S185), and serine 232 (S232). METHODS: S58, S185, and S232 phosphorylation was
measured by western blot analysis of Triton X-100 soluble and insoluble fractions
from postmortem temporal cortex. RESULTS: The ratio of soluble phospho-S232 to
insoluble phospho-S232 was reduced by 32%, 60%, 37%, and 52% in PD, AD, ADLB, and
DLB, respectively. S185 and S58 phosphorylation were mildly elevated in the
soluble fraction in DLB. We also noted a dramatic reduction in soluble pan 14-3-3
levels by ~35% in AD, ADLB, and DLB. Lower ratios of soluble to insoluble S232
phosphorylation (pointing to higher insoluble pS232) correlated with lower
soluble pan 14-3-3 levels, suggesting that S232 phosphorylation may promote
insolubilization of 14-3-3s. The phospho-S232 ratio and soluble pan 14-3-3 levels
correlated with clinical and pathological severity. INTERPRETATION: These data
reveal dysregulation of 14-3-3 proteins in neurodegeneration associated with Lewy
body or Alzheimer pathology. S232 phosphorylation may drive insolubilization of
14-3-3s and thus contribute to the pathophysiology in neurodegenerative disorders
associated with Lewy body or Alzheimer pathology.
PMID- 28695148
TI - Pharmacodynamic effects of daclizumab in the intrathecal compartment.
AB - OBJECTIVE: It was previously demonstrated that daclizumab therapy normalizes
cellular cerebrospinal fluid (CSF) abnormalities typical of multiple sclerosis
(MS) in the majority of treated patients. However, CSF cells represent only the
mobile portion of intrathecal immune responses. Therefore, we asked whether
daclizumab also reverses compartmentalized inflammation and if not, whether
residual inflammation correlates with clinical response to the drug. METHODS:
Forty MS patients treated with an intravenous or subcutaneous injection of
daclizumab were followed for up to 16 years in two open-label clinical trials.
MRI contrast-enhancing lesions (CELs), clinical scales, and CSF biomarkers
quantified residual disease. RESULTS: Rapid decreases in CELs, sustained
throughout the observation period, were observed with daclizumab treatment.
Daclizumab therapy induced modest but statistically significant (P < 0.0001)
decreases in CSF levels of T-cell activation marker CD27 and IgG index.
Interleukin 2 (IL-2) CSF levels increased from baseline levels during treatment,
consistent with reduced IL-2 consumption by T cells, as a consequence of
daclizumab's saturation of high-affinity IL-2 receptors. CSF levels of IL-12p40,
chitinase-3-like protein-1 (CHI3L1), chemokine C-X-C motif ligand 13, and
neurofilament light chain (NFL) were also significantly reduced by daclizumab.
Among them, inhibition of CHI3L1 correlated with inhibition of NFL and with lack
of disease progression. INTERPRETATION: These observations confirm daclizumab's
direct pharmacodynamics effects on immune cells within central nervous system
tissues and identify inhibition of CSF biomarkers of myeloid lineage as a
stronger determinant of reduction in clinical MS activity than inhibition of
biomarkers of adaptive immunity.
PMID- 28695149
TI - Low-dose suramin in autism spectrum disorder: a small, phase I/II, randomized
clinical trial.
AB - OBJECTIVE: No drug is yet approved to treat the core symptoms of autism spectrum
disorder (ASD). Low-dose suramin was effective in the maternal immune activation
and Fragile X mouse models of ASD. The Suramin Autism Treatment-1 (SAT-1) trial
was a double-blind, placebo-controlled, translational pilot study to examine the
safety and activity of low-dose suramin in children with ASD. METHODS: Ten male
subjects with ASD, ages 5-14 years, were matched by age, IQ, and autism severity
into five pairs, then randomized to receive a single, intravenous infusion of
suramin (20 mg/kg) or saline. The primary outcomes were ADOS-2 comparison scores
and Expressive One-Word Picture Vocabulary Test (EOWPVT). Secondary outcomes were
the aberrant behavior checklist, autism treatment evaluation checklist,
repetitive behavior questionnaire, and clinical global impression questionnaire.
RESULTS: Blood levels of suramin were 12 +/- 1.5 MUmol/L (mean +/- SD) at 2 days
and 1.5 +/- 0.5 MUmol/L after 6 weeks. The terminal half-life was 14.7 +/- 0.7
days. A self-limited, asymptomatic rash was seen, but there were no serious
adverse events. ADOS-2 comparison scores improved by -1.6 +/- 0.55 points (n = 5;
95% CI = -2.3 to -0.9; Cohen's d = 2.9; P = 0.0028) in the suramin group and did
not change in the placebo group. EOWPVT scores did not change. Secondary outcomes
also showed improvements in language, social interaction, and decreased
restricted or repetitive behaviors. INTERPRETATION: The safety and activity of
low-dose suramin showed promise as a novel approach to treatment of ASD in this
small study.
PMID- 28695150
TI - Cladribine to treat disease exacerbation after fingolimod discontinuation in
progressive multiple sclerosis.
AB - Rebound disease following cessation of disease modifying treatment (DMT) has been
reported in people with both relapsing and progressive multiple sclerosis (pwRMS,
pwPMS) questioning strict separation between these two phenotypes. While licensed
DMT is available for pwRMS to counter rebound disease, no such option exists for
pwPMS. We report on a pwPMS who developed rebound disease, with 45 Gadolinium
enhancing lesions on T1 weighted MRI brain, within 6 months after fingolimod 0.5
mg/day was stopped. Treatment with a short course of subcutaneous cladribine 60
mg led to effective suppression of inflammatory activity and partial recovery
with no short-term safety issues or adverse events.
PMID- 28695151
TI - Glioblastoma in natalizumab-treated multiple sclerosis patients.
AB - We present two natalizumab-treated multiple sclerosis patients who developed
glioblastoma multiforme (GBM) with variable outcomes. One patient had an
isocitrate dehydrogenase (IDH)-wildtype GBM with aggressive behavior, who
declined treatment and died 13 weeks after symptoms onset. The other patient
underwent resection of an IDH-mutant secondary GBM that arose from a previously
diagnosed grade II astrocytoma. He is still alive 5 years after the diagnosis of
GBM. JC virus was not detected in either case. Whether natalizumab played a role
in the development of GBM in those patients deserves further investigation.
PMID- 28695152
TI - Proximal flow to middle cerebral artery is associated with higher thrombus
density in terminal internal carotid artery occlusion.
AB - Proximal collaterals may determine the composition of occluding thrombi in acute
ischemic stroke (AIS) in addition to source, hematocrit, time, and medication.
Here, we performed a retrospective study of 39 consecutive patients with
radiological evidence of I-, L-, and T-type terminal internal carotid artery
occlusion. Middle cerebral artery (MCA) thrombus density was assessed on
noncontrast enhanced CT and proximal collaterals on CT angiography. In patients
with presence of proximal collaterals to the MCA we detected more hyperdense
clots (P = 0.003) and a higher frequency of leptomeningeal collaterals (P =
0.008). We expand the spectrum of factors that potentially determine clot
perviousness and evolution of ischemic stroke.
PMID- 28695153
TI - New insights into SMA pathogenesis: immune dysfunction and neuroinflammation.
AB - Spinal muscular atrophy (SMA) is a neuromuscular disorder characterized by motor
neuron degeneration, although defects in multiple cell types and tissues have
also been implicated. Three independent laboratories recently identified immune
organ defects in SMA. We therefore propose a novel pathogenic mechanism
contributory to SMA, resulting in higher susceptibility to infection and
exacerbated disease progression caused by neuroinflammation. Overall, compromised
immune function could significantly affect survival and quality of life of SMA
patients. We highlight the recent findings in immune organ defects, their
potential consequences on patients, our understanding of neuroinflammation in
SMA, and new research hypotheses in SMA pathogenesis.
PMID- 28695154
TI - The Role of Minority Stressors in Lesbian Relationship Commitment and Persistence
over Time.
AB - The Investment Model of relationship commitment uses interpersonal investment,
relationship satisfaction, quality of alternatives, and commitment to predict
relationship longevity (Rusbult, 1980, 1983). Although ample support for the
Investment Model has been found in heterosexual couples, it appears to be less
powerful in predicting stability in same-sex relationships (Beals, Impett, &
Peplau, 2002), potentially because the model does not account for factors unique
to same-sex relationships, such as anti-gay discrimination. However, no research
has tested the nature and power of sexual minority stress factors in predicting
same-sex relationship stability over time. Using secondary, longitudinal data
collected from a diverse sample of lesbian women in relationships (N = 211), we
examined how internalized homonegativity, sexual identity disclosure, and
workplace discrimination affected the Investment Model antecedents of
relationship persistence: satisfaction, quality of alternatives, and investment.
We tested the influence of sexual minority stressors on Investment Model
processes using structural equations modeling and found that sexual identity
disclosure was positively associated with satisfaction and investment,
internalized homonegativity was only negatively associated with satisfaction and
investment, while workplace discrimination was negatively associated with
alternatives. Moreover, both relationship satisfaction and investment influenced
commitment which predicted persistence in these relationships over about seven
years' time, demonstrating support for the Investment Model. Our findings support
the addition of sexual minority stress variables to the Investment Model when
examining same-sex relationships and implications are discussed.
PMID- 28695155
TI - In Silico Restriction Enzyme Digests to Minimize Mapping Bias in Genomic
Sequencing.
PMID- 28695156
TI - Extending the concept of weighted CT dose index to elliptical phantoms of various
aspect ratios.
AB - The purpose of this study was to extend the concept of weighted CT dose index
([Formula: see text]) to the elliptical phantoms. Based on the published body
dimension data, eight body aspect ratios were chosen between 1 (perfectly
circular) and 1.72 (extremely elliptical). For each aspect ratio, two elliptical
cylinders were created digitally to represent adult and pediatric bodies. Their
cross-sectional areas were identical to the standard 32- and 16-cm CTDI phantoms.
For each phantom, [Formula: see text] at center and periphery were simulated for
tube voltages between 70 and 140 kVp using a validated Monte Carlo program. The
simulations also provided the average dose over the cross-sectional area,
[Formula: see text]. Values of [Formula: see text] and [Formula: see text]
allowed linear systems of equations to be established, from which central and
peripheral weighting coefficients were solved. Regardless of phantom shape, only
two weighting coefficients were needed: [Formula: see text] for the central
[Formula: see text] and [Formula: see text] for the average of the four
peripheral [Formula: see text]'s. Over the full range of aspect ratios, [Formula:
see text] increased linearly from 0.37 to 0.46, whereas [Formula: see text]
decreased linearly from 0.63 to 0.54, allowing the concept of [Formula: see text]
to be readily extended to the elliptical phantoms. When cross-sectional area
(hence volume) was kept constant, all phantoms had the same [Formula: see text]
regardless of shape.
PMID- 28695157
TI - Lipoprotein Lipase Deficiency in an Infant With Chylomicronemia, Hepatomegaly,
and Lipemia Retinalis.
PMID- 28695158
TI - The Role of Genetic Testing in Hereditary Poikiloderma: A Case Report.
PMID- 28695159
TI - An 11-Year-Old Boy With Ear Pain and Facial Palsy.
PMID- 28695161
TI - Retinoblastoma: Making a Difference Together.
AB - Mary Elizabeth is an Oncology Clinical Nurse Specialist from Memorial Sloan
Kettering Cancer Center in New York City, New York. She graduated from University
of Delaware in 1985, with a Bachelor's degree in nursing and followed in 1989,
with a Masters of Nursing from Columbia University specializing in oncology. Mary
Elizabeth works as a Clinical Nurse Specialist in Memorial Sloan Kettering's
ambulatory medical oncology consultative services. Her role includes modeling
professional practice to the nurses of the services for which she has
responsibility including mentoring and precepting nurses who are new to a
practice, coordinating and evaluating their clinical experiences, and overseeing
their development in the oncology nursing specialty and the ambulatory clinical
practice role. Mary Elizabeth regularly "walks the walk" filling in and assisting
in busy practices; this helps her maintain knowledge of the latest advances in
disease management as well as experience firsthand the challenges of the
ambulatory nursing role. Over the past few years, she has been practicing within
MSK's busy and growing world - renowned retinoblastoma (RB) clinic. Mary
Elizabeth has presented on RB nationally and at international conferences in the
hopes of bringing this curable disease to the attention of nurses worldwide.
Early diagnosis and early access to treatment can save lives, eyes, and vision.
PMID- 28695160
TI - Recent advances in nonbiofouling PDMS surface modification strategies applicable
to microfluidic technology.
AB - In the last decade microfabrication processes including rapid prototyping
techniques have advanced rapidly and achieved a fairly mature stage. These
advances have encouraged and enabled the use of microfluidic devices by a wider
range of users with applications in biological separations and cell and organoid
cultures. Accordingly, a significant current challenge in the field is
controlling biomolecular interactions at interfaces and the development of novel
biomaterials to satisfy the unique needs of the biomedical applications.
Poly(dimethylsiloxane) (PDMS) is one of the most widely used materials in the
fabrication of microfluidic devices. The popularity of this material is the
result of its low cost, simple fabrication allowing rapid prototyping, high
optical transparency, and gas permeability. However, a major drawback of PDMS is
its hydrophobicity and fast hydrophobic recovery after surface hydrophilization.
This results in significant nonspecific adsorption of proteins as well as small
hydrophobic molecules such as therapeutic drugs limiting the utility of PDMS in
biomedical microfluidic circuitry. Accordingly, here, we focus on recent advances
in surface molecular treatments to prevent fouling of PDMS surfaces towards
improving its utility and expanding its use cases in biomedical applications.
PMID- 28695162
TI - Management of Retinoblastoma in Zambia.
PMID- 28695163
TI - Influence of Socioeconomic and Cultural Factors on Retinoblastoma Management.
PMID- 28695164
TI - Psychosocial Factors Influencing Parental Decision to Allow or Refuse Potentially
Lifesaving Enucleation in Children with Retinoblastoma.
AB - OBJECTIVE: Retinoblastoma is the most common malignancy of the eye and ocular
adnexa in the Philippines. It is curable when treated early, but delay in
enucleation is common due to the parental refusal of surgery for varied reasons.
The aim of this study is to identify the psychosocial barriers and facilitating
factors for accepting versus refusing enucleation as treatment for
retinoblastoma. METHODS: This is a cross-sectional descriptive study utilizing
structured interviews and a questionnaire. It was conducted at the Retinoblastoma
Clinic of the Philippine General Hospital. A questionnaire using the Likert scale
was constructed after performing key informant interviews and focus group
discussions. It was pretested and revised before parents of patients with
retinoblastoma were invited to participate in the study. Descriptive statistics,
quantitative item analyses using inter-item correlations and item-total
correlations was performed. RESULTS: Factors that correlate with refusal to
enucleate are the beliefs that cancer is a fatal illness, the fear of
unacceptable esthetic outcome of the surgery, and the cost of treatment.
Favorable factors include value of life, high regard for the opinion of medical
practitioners, and appreciation of the efficacy of treatment. CONCLUSIONS: There
are several favorable factors and barriers that health practitioners must
consider in facilitating parental decision-making toward enucleation for
retinoblastoma.
PMID- 28695165
TI - Neonatal Retinoblastoma.
AB - From 7% to 10% of all retinoblastomas and from 44% to 71% of familial
retinoblastomas in developed countries are diagnosed in the neonatal period,
usually through pre- or post-natal screening prompted by a positive family
history and sometimes serendipitously during screening for retinopathy of
prematurity or other reasons. In developing countries, neonatal diagnosis of
retinoblastoma has been less common. Neonatal retinoblastoma generally develops
from a germline mutation of RB1, the retinoblastoma gene, even when the family
history is negative and is thus usually hereditary. At least one-half of infants
with neonatal retinoblastoma have unilateral tumors when the diagnosis is made,
typically the International Intraocular Retinoblastoma Classification (Murphree)
Group B or higher, but most germline mutation carriers will progress to bilateral
involvement, typically Group A in the fellow eye. Neonatal leukokoria usually
leads to the diagnosis in children without a family history of retinoblastoma,
and a Group C tumor or higher is typical in the more advanced involved eye.
Almost all infants with neonatal retinoblastoma have at least one eye with a
tumor in proximity to the foveola, but the macula of the fellow eye is frequently
spared. Consequently, loss of reading vision from both eyes is exceptional. A
primary ectopic intracranial neuroblastic tumor known as trilateral
retinoblastoma is no more common after neonatal than other retinoblastoma. For
many reasons, neonatal retinoblastoma may be a challenge to eradicate, and the
early age at diagnosis and relatively small tumors do not guarantee the
preservation of both eyes of every involved child. Oncology nurses can be
instrumental in contributing to better outcomes by ensuring that hereditary
retinoblastoma survivors receive genetic counseling, by referring families of
survivors to early screening programs when they are planning for a baby, and by
providing psychological and practical support for parents when neonatal
retinoblastoma has been diagnosed.
PMID- 28695166
TI - Ophthalmic Artery Chemosurgery: A Nursing Perspective.
AB - Retinoblastoma (RB) is the most common primary cancer to affect the eyes in
children with approximately 350 cases/year in the United States and 8000
worldwide. Today, sadly, 50% of children with RB worldwide die from their
disease. In our experience, utilization of ophthalmic artery chemosurgery (OAC)
has transformed the treatment plan for patients; with over 1500 procedures
performed, our survival rate exceeds 98%. It is now our standard first-line
therapy for RB. OAC is a surgical outpatient procedure which delivers
concentrated doses of chemotherapy directly to the tumor without the toxicities
of systemic chemotherapy. Our team approach and nursing management of these
patients are the focus of this article. Nursing navigation and collaboration
after OAC is vital and requires a combined effort by the nurses along with
physicians, interventional radiologists, and the patient's families to ensure
appropriate follow-up is established. Proper patient education throughout the
process is crucial as is open and available communication for parents of patients
with the nursing staff. The success in our treatment of this disease can be much
accredited to the multidisciplinary team approach, with nursing playing an
integral part in the support and management of these patients.
PMID- 28695167
TI - Cancer and Palliative Care in the United States, Turkey, and Malawi: Developing
Global Collaborations.
AB - As the global cancer burden grows, so too will global inequities in access to
cancer and palliative care increase. This paper will describe the cancer and
palliative care landscape relative to nursing practice, education, and research,
and emerging global collaborations in the United States (U.S.), Turkey, and
Malawi. It is imperative that nurses lead efforts to advance health and
strengthen education in these high-need areas. Leaders within the University of
Alabama at Birmingham School of Nursing, through a Pan American Health
Organization/World Health Organization Nursing Collaborating Center, have
initiated collaborative projects in cancer and palliative care between the U.S.,
Turkey, and Malawi to strengthen initiatives that can ultimately transform
practice. These collaborations will lay a foundation to empower nurses to lead
efforts to reduce the global inequities for those with cancer and other serious
and life-limiting illnesses.
PMID- 28695168
TI - Living with the Effects of Cutaneous Toxicities Induced by Treatment.
AB - The introduction of targeted therapies in cancer treatment was accompanied with
promising results including tumor control and patients survival benefits.
However, these drugs just like their predecessors were associated with systemic
side effects, including frequent and various cutaneous effects. Targeted
therapies such as epidermal growth factor receptor, vascular endothelial growth
factor receptor, kit, platelet-derived growth factor receptor, and BCR-ABL
inhibitors as well as mammalian target of rapamycin inhibitors can induce
cutaneous toxicities of varying severity. There are scarce studies on the actual
impact of these toxicities on the patients' lives including the physical, social,
and psychological aspects and overall quality of life. Patient's perspective in
living with and beyond these toxicities remains largely uncharted but essential
in optimizing care provided to those receiving treatment with targeted therapies.
PMID- 28695169
TI - Chemotherapy and Glycemic Control in Patients with Type 2 Diabetes and Cancer: A
Comparative Case Analysis.
AB - OBJECTIVE: Individuals with diabetes who develop cancer have a worse 5-year
overall survival rate and are more likely to develop an infection and/or be
hospitalized when compared to those without diabetes. Patients with diabetes and
cancer receiving chemotherapy have an increased risk for developing glycemic
issues. The relationship between chemotherapy and glycemic control is not
completely understood. The aim of this study was to explore the relationship
between glycemic control, symptoms, physical and mental function, development of
adverse events, and chemotherapy reductions or stoppages in adults with Type 2
diabetes (T2D) and cancer. METHODS: A prospective 12-week longitudinal cohort
study recruited 24 adults with T2D, solid tumor cancer, or lymphoma receiving
outpatient intravenous chemotherapy. Eighteen individuals completed baseline data
and were included in the analysis. A comparative case analysis was performed to
analyze the results. RESULTS: Potential predictors of occurrence of an adverse
event include sex (relative risk [RR] = 1.5), treatment with insulin (RR = 2.17),
years with diabetes (RR = 3.85), and baseline glycated hemoglobin (HbA1c) (odds
ratio [OR] = 1.67). Baseline body mass index (BMI) (OR = 1.16) and HbA1c (OR =
1.61) were potentially predictive of a chemotherapy stoppage. CONCLUSIONS: Level
of glycemic control at the time an individual begins treatment for cancer appears
to contribute to the occurrence of an adverse event, developing an infection
and/or being hospitalized during treatment, and the increased risk of having a
chemotherapy reduction or stoppage. Clinicians working with patients receiving
chemotherapy for a solid tumor cancer who have pre-existing diabetes, need to be
aware of how the patients glycemic level at the start of treatment may impact
successful treatment completion.
PMID- 28695170
TI - Emotional Responses to Persistent Chemotherapy-induced Peripheral Neuropathy
Experienced by Patients with Colorectal Cancer in Japan.
AB - OBJECTIVE: For patients who wish to continue treatment for persistent
chemotherapy-induced peripheral neuropathy (PCIPN) while maintaining the quality
of life (QOL), the only effective way appears to be the stop-and-go strategy. The
objective of the present study was to analyze emotional responses of Japanese
patients with colorectal cancer (CRC) experiencing PCIPN for the first time and
to consider effective ways of providing supportive nursing care. METHODS: In all,
25 patients with metastatic CRC who had completed more than six courses receiving
first-line therapy with modified FOLFOX6 were included. Data were collected
through semi-structured interviews. RESULTS: Emotional responses to PCIPN
experienced by patients with CRC fell into the following categories: (1)
suffering from an inability to cope with the previously unknown sensation of
numbness, (2) inability to perform daily living activities activities of daily
living [ADL]/instrumental activities of daily living [IADL] independently and
feeling fear for physical safety, (3) feeling a sense of relief at being able to
live the same life as before, and (4) facing the threat of cancer and tolerating
the numbness caused by the life-supporting treatment. Fear, helplessness, dismay
and other uncomfortable feelings represented 72.5% of all emotional responses,
probably reflecting the lack of effective intervention for PCIPN. CONCLUSIONS:
These results suggest that both subjective and objective assessments of PCIPN and
proper use of a stop-and-go strategy are essential for treatment continuation and
maintenance of patient's QOL; therefore, an integrated approach is desirable.
PMID- 28695171
TI - The Effect of Reflexology on Chemotherapy-induced Nausea, Vomiting, and Fatigue
in Breast Cancer Patients.
AB - OBJECTIVE: Patients receiving chemotherapy struggle with the side effects of this
treatment. These side effects obligate the patients to use not only the
pharmacological methods but also non-pharmacological relaxing methods. This study
was conducted to determine the effect of reflexology on chemotherapy-induced
nausea, vomiting, and fatigue in breast cancer patients. METHODS: The study was
conducted as a pretest-posttest experimental design. The study was conducted with
sixty patients, thirty as the control and thirty as the experimental groups. A
sociodemographic form, Rhodes index of nausea, vomiting, and retching (INVR), and
Brief Fatigue Inventory (BFI) were used to collect the data. Analysis of
variance, t-test, percentage calculations, and Chi-square methods were used to
evaluate the data. The data obtained were assessed using the "Statistical Package
for Social Science 21.0" software. RESULTS: It was determined that the difference
between the total mean scores of INVR in the experimental and control groups was
significant on the onset and first and second measurements, and the difference
between total mean scores of development and distress between the groups was
statistically significant in the third measurement (P < 0.05). The results of the
study showed that the BFI mean scores of patients in the experimental group
gradually decreased in the first, second, and third measurements (P < 0.05).
CONCLUSIONS: The present study proved that reflexology decreased the experience,
development, distress of nausea, vomiting, and retching as well as fatigue in the
experimental group. Hence, the use of reflexology is recommended for chemotherapy
induced nausea, vomiting, and fatigue.
PMID- 28695172
TI - Women Experiences of Using External Breast Prosthesis after Mastectomy.
AB - OBJECTIVE: The aim of this study was to identify the experiences of breast cancer
patients using external breast prostheses (EBP) in the context of the Pakistani
society. METHODS: A qualitative descriptive exploratory design was used in the
study. In-depth individual interviews were conducted with 15 postmastectomy women
using EBP. A semi-structured interview guide with open-ended questions was used
for the interviews. The analysis of the data was organized into four categories
according to the study questions including reasons for using EBP, feeling about
EBP, challenges for using EBP, and coping with lost breast. Each category was
further divided into subcategories. RESULTS: Women used EBP because they felt
strange, incomplete, and embarrassed in front of other people, due to the
asymmetrical shape of the chest after mastectomy. They faced several challenges
with regard to obtaining and using the EBP. While EBP was used as an alternative
of their lost breast, they experienced sadness and embarrassment. They found it
challenging to take care of the EBP and were required to make changes in their
lifestyle. However, they accepted living with their lost breast, either through
rationalization, family support, or faith and prayers, which helped them to cope.
CONCLUSIONS: The study findings have given insight into some real experiences of
mastectomy patients. Mastectomy not only affects women's physical health but also
their psychological health, as a result of which they become reluctant to
socialize. Using EBP can help them to improve their body image and body posture.
Health-care providers' support is very important to the families of the patients
specifically where patients are very shy to openly seek information due to
cultural constraints.
PMID- 28695173
TI - Identification of Symptom Clusters in Cancer Patients at Palliative Care Clinic.
AB - OBJECTIVE: Cancer patients often experience a large number of symptoms together.
The aim of this study is to determine the symptom clusters in cancer patients at
palliative care clinic. METHODS: Hundred and seventy consecutive patients were
enrolled in the study. Memorial Symptom Assessment Scale was used for symptom
assessment of the patients. RESULTS: The most experienced symptoms by the
patients during the past week before hospitalization in palliative care clinic
were lack of energy (95.4%), weight loss (91.2%), lack of appetite (89.4%), pain
(88.2%), dry mouth (87.6%), feeling sad (87.6%), feeling nervous (82.9%),
worrying (81.2%), and feeling irritable (80.6%). Five symptom clusters were
defined. First cluster: pain, feeling nervous, dry mouth, worrying, feeling
irritable, weight loss; second cluster: feeling drowsy, numbness/tingling in
hands/feet, difficulty in sleeping, dizziness, constipation, I do not look like
myself; third cluster: nausea, vomiting; fourth cluster: shortness of breath,
difficulty in swallowing, cough, change in the way food tastes; and fifth
cluster: feeling bloated, problems with urination, diarrhea, itching, mouth
sores, hair loss, swelling of arm or legs, change in the skin. CONCLUSIONS: We
encountered various symptom clusters in advanced cancer patients. Identification
of symptom clusters and knowledge of cluster composition in oncological
population may particularly contribute individualization of the treatment.
PMID- 28695174
TI - A Patient with Cancer and Her Family in Caring Partnership Based on Margaret
Newman's Theory of Health as Expanding Consciousness.
AB - The purpose, on the basis of Margaret Newman's theory of health as expanding
consciousness in a unitary perspective, was to practice the caring partnership
with a client who could not share their desires and find their future direction
at a gear change period and document the process of their relational changes
within this process. The design was research as praxis. The participant was a
patient with cancer and her family in the midst of a difficult health situation.
Through caring partnership, a nurse researcher asked to tell "the meaningful
events and relationships in their lives" over four in-depth dialogue meetings.
Data were collected from the tape-recorded dialogue transcriptions. In the
process of caring partnership, the patient and each family member recognized
their own pattern and family pattern of "being closed off," their approach to the
situation, and found a new direction through this process. The finding suggested
that caring partnership as a nursing intervention would be helpful for nurses as
well as for patients and their families in difficult health situations.
PMID- 28695175
TI - Follicular Thyroid Carcinoma Presenting as Large Solitary Vertebral Metastasis:
Report of Two Unusual Cases Treated with Radiotherapy.
AB - Solitary spinal metastasis with cord compression as the presenting feature of
follicular thyroid carcinoma (FTC) is extremely unusual with <10 cases reported
in world literature. We hereby present two such cases in a 39-year-old male with
lytic lesion left sacral bone with biopsy showing metastatic carcinoma with
morphology and immunophenotype of thyroid gland and a 35-year-old female with
thoracic vertebral lesions suggestive of metastatic deposit of FTC. Subsequently,
both patients were found to have a solitary nodule in the thyroid lobe. They were
treated with local radiotherapy (RT) with significant symptomatic relief. The
present cases highlight the rarity of FTC to present as upfront solitary
vertebral metastases with significant morbidity in young individuals although a
slow indolent course with metastases in late stages of disease is more common,
debilitating the effect of metastatic lesion requiring RT for pain palliation and
the role of supportive nursing care for patient rehabilitation.
PMID- 28695176
TI - The American Joint Replacement Registry-the first 5 years.
PMID- 28695177
TI - Unusual presentation of failed metal-on-metal total hip arthroplasty with
features of neoplastic process.
AB - Metal-on-metal (MoM) total hip arthroplasty (THA) is associated with increased
incidence of failure from metallosis, adverse tissue reactions, and the formation
of pseudotumors. This case highlights a 53-year-old female with an enlarging
painful thigh mass 12 years status post MoM THA. Radiographs and advanced imaging
revealed an atypical mass with cortical bone destruction and spiculation,
concerning for periprosthetic malignancy. Open frozen section biopsy was
performed before undergoing revision THA in a single episode of care. This case
illustrates that massive pseudotumors can be locally aggressive causing
significant femoral bone destruction and may mimic malignancy. It is important
that orthopaedic surgeons, radiologists and pathologists understand the relative
infrequency of periprosthetic malignancy in MoM THA to mitigate patient concerns,
misdiagnosis, and allow for an evidence based discussion when treating massive
pseudotumors.
PMID- 28695178
TI - Delayed diagnosis of catastrophic ceramic liner failure with resultant pelvic
discontinuity and massive metallosis.
AB - With newer-generation ceramic components used in total hip arthroplasty,
component fracture is a rare complication. However rare, when ceramic component
fracture does occur, prompt identification and revision is necessary as delay can
lead to dramatic failure with resultant metallosis as the extremely hard ceramic
debris abrades remaining components. We present a case of a 70-year-old woman
with ceramic liner fracture and an estimated 10-year delay in intervention with
failure resulting in pelvic discontinuity and massive metallosis with associated
cutaneous manifestation. She was treated with a complex revision and
reconstruction and is 2 years postrevision without major complication.
PMID- 28695179
TI - Inflammatory pseudotumor after ceramic-on-ceramic total hip arthroplasty.
AB - We present a unique case of a symptomatic adverse local tissue reaction in a
patient with a ceramic-on-ceramic total hip bearing surface. To our knowledge,
this pathological finding has not yet been described in a ceramic-on-ceramic
articulation without a cobalt-chromium alloy trunnion or modular neck component
as a source of metal wear. We conclude that despite its mechanical mostly benign
wear characteristics, ceramic wear debris is not entirely inert and may lead to
the development of adverse local tissue reaction.
PMID- 28695180
TI - Custom hemiarthroplasties for retention of existing hardware associated with
osteogenesis imperfecta.
AB - Osteogenesis imperfecta is a rare genetic disorder that presents with
heterogeneous phenotypes ranging from brittle bones to impaired hearing. Because
of the decreased bone mineral density frequently observed in this patient
population, many patients experience recurring and long-term fractures, which
often require orthopaedic management. With the advancement of nonsurgical and
surgical management and increased longevity of patients with osteogenesis
imperfecta, the incidence of osteoarthritis has risen, presenting new orthopaedic
challenges. However, compromised bone integrity and size combined with frequent
existing hardware render traditional surgical therapies for osteoarthritis
technically challenging in this patient population. In this report, we present a
case in which we retained a portion of the patient's existing hardware, while
performing staged bilateral custom hemiarthroplasties in a patient with
osteogenesis imperfecta.
PMID- 28695181
TI - Prepping the knee in maximal flexion: getting into every nook, cranny, and fold.
AB - This article describes a simple surgical skin preparation technique for total
knee arthroplasty that permits the application of skin prep agent with the knee
in maximal flexion. While most surgeons prep the knee in extension, it is
believed that prep of the knee in flexion will provide superior coverage of the
skin surface and reduce the potential for surgical-site infection, particularly
in obese patients with large soft-tissue layers anterior to the knee.
PMID- 28695182
TI - Adolescent total knee arthroplasty.
AB - BACKGROUND: Management of adolescent patients with end-stage arthritis is
challenging. Nonoperative treatments may be ineffective and total knee
arthroplasty (TKA) is rarely performed. Currently, minimal long-term data are
available on the outcomes in this patient population. Our goal was to describe
TKA for patients with end-stage arthritis who were aged 20 years and younger.
METHODS: The Joint Registry at our institution was used to identify 19 patients
(29 TKAs) aged 20 years and younger that underwent a primary TKA. The average age
was 18 years (range 14-20 years) and follow-up was 14.5 years (range: 2.1-25.5
years). RESULTS: The preoperative diagnoses were juvenile idiopathic arthritis (n
= 19), avascular necrosis (n = 4), sepsis (n = 2), trauma (n = 2), dysplasia (n =
1), and hemophilia (n = 1). There was a decrease in the number of TKAs performed
for inflammatory arthritis over the last several decades. Implant survivorship at
5 and 10 years was 96% and 94%, respectively. CONCLUSIONS: We identified a 95% 10
year implant survivorship utilizing standard TKA components in pediatric
patients. Performing a TKA in adolescent patients has long-term potential risks
including infection and bone loss but may provide pain relief and good long-term
results and should be used with caution.
PMID- 28695183
TI - A randomized controlled trial to compare component placement in navigated total
knee arthroplasty using original and streamlined registration processes.
AB - BACKGROUND: This randomized controlled trial validated a redesigned version of
navigated total knee arthroplasty software with a streamlined registration
(Smart) against the previous version (Classic). The objectives were to determine
if Smart software had the same accuracy of component positioning and whether
registration and operative time were reduced. METHODS: A total of 220 patients
were recruited and had a navigated total knee arthroplasty performed. With the
exception of the software, all patients had the same perioperative care. At 6
week follow-up with an independent arthroplasty service, all patients had a
computerized tomography scan. This was assessed by an independent radiologist to
measure the mechanical alignment of the components. RESULTS: The mean
postoperative mechanical femorotibial angles were equivalent between groups (mean
difference -0.2 degrees , 95% confidence interval -0.7 degrees to 0.3 degrees ,
P = .407). Component positions were similar in both groups. Mean registration
time was significantly shorter for the Smart group (2 minutes 30 seconds +/- 54
seconds) than the Classic group (3 minutes 23 seconds +/- 39 seconds), P < .001.
The mean operative time was 72 +/- 12 minutes in both groups (P = .855). At 6
week follow-up, both groups had similar clinical outcomes with 96.5% of patients
being satisfied or very satisfied. CONCLUSIONS: The study verified that a reduced
registration time did not alter the accuracy of component placement. However,
despite a shorter registration time, the overall surgical time was not reduced.
PMID- 28695184
TI - The stability of dual-taper modular hip implants: a biomechanical analysis
examining the effect of impact location on component stability.
AB - BACKGROUND: The purpose of this study was to investigate the stability of dual
taper modular implants following impaction forces delivered at varying locations
as measured by the distraction forces required to disassemble the components.
METHODS: Distraction of the head-neck and neck-stem (NS) tapers of dual-taper
modular implants with 0 degrees , 8 degrees , and 15 degrees neck angles were
measured utilizing a custom-made distraction fixture attached to a servohydraulic
materials test machine. Distraction was measured after hand pressing the
components as well as following a simulated firm hammer blow impaction. Impacts
to the 0 degrees , 8 degrees , 15 degrees necks were directed axially in line
with the neck, 10 degrees anterior, and 10 degrees proximal to the axis of the
neck, respectively. RESULTS: Impaction increased the range of NS component
distraction forces when compared to hand pressed components (1125-1743 N vs 248
302 N, respectively). Off-axis impacts resulted in significantly reduced mean (+/
95% confidence interval) distraction forces (8 degrees neck, 1125 +/- 117 N; 15
degrees neck, 1212 +/- 73 N), which were up to 35% lower than the mean
distraction force for axial impacts to the 0 degrees neck (1743 +/- 138 N).
CONCLUSIONS: Direction of impaction influences stability of the modular
interface. The greatest stability was achieved with impaction directed in line
with the longitudinal axis of the taper junction. Off-axis impaction of the 8
degrees and 15 degrees neck led to significantly reduced stability at the NS.
Improving stability of dual-taper modular hip prostheses with appropriately
directed impaction may help to minimize micromotion, component settling, fretting
corrosion, and subsequent failure.
PMID- 28695185
TI - Prospective quality of life assessment after hip and knee arthroplasty: short-
and mid-term follow-up results.
AB - BACKGROUND: Hip and knee arthroplasty aims to restore the joint function and to
improve health-related quality of life (HRQoL) in patients with articular damage.
It is important to quantify the HRQoL improvement and when this is achieved. The
Oxford knee score and the Oxford hip score were developed to evaluate patients
after knee and hip arthroplasty. We sought to evaluate HRQoL changes in the short
and mid term following either primary or revision hip and knee arthroplasty.
METHODS: Prospective cohort study during a 20-month period (August 2013 to March
2015) in a tertiary referral hospital. Primary arthroplasties secondary to
osteoarthritis and any-cause revisions were included (328, 160 knees, and 88
hips). They were divided into 4 groups: (1) primary knee replacement, (2) primary
hip replacement, (3) revision knee replacement, and (4) revision hip replacement.
Oxford knee and hip scores were obtained prior the surgery and compared with the
short- and mid-term follow-up scores. RESULTS: Follow-up in the short term and
mid term was: 75.6% and 67.4%, respectively. Improvement was found in both short
term and mid-term follow-up for each group and for the overall group in HRQoL as
measured by the Oxford knee and hip scores (P < .001). The greatest improvement
was seen in the short term with an increase of 21 points for primary knee
arthroplasty; 24 points for primary hip arthroplasty; 22 points for revision knee
arthroplasty; and 23 points for revision hip arthroplasty. CONCLUSIONS:
Improvement in HRQoL in patients following primary or revision hip or knee
arthroplasty is crucial and can be achieved early after the surgery.
PMID- 28695186
TI - Hemispherical and minimally invasive total hip reamers: a biomechanical analysis
of use and design.
AB - BACKGROUND: The purpose of this study was to determine the accuracy of used and
new reamer systems for both hemispherical and minimally invasive (MIS) acetabular
reamers. METHODS: New and used hemispherical and MIS acetabular reamers were
tested on a computer numerical control machine to ream holes in special
machinable wax blocks. Each reamer was tested 3 times in sizes 48 mm through 55
mm. RESULTS: The used reamers significantly underreamed by an average of 1.33 vs
0.28 mm compared to new reamers. Hemispherical reamers underreamed significantly
more than MIS reamers, with a mean difference of 0.99 vs 0.63 mm, respectively.
Used hemispherical reamers showed an average ream undersize of 1.61 vs 0.37 mm,
compared to new hemispherical reamers. Used MIS reamers showed an average ream
undersize of 1.06 vs 0.20 mm for the new MIS reamers. CONCLUSIONS: For a
manufacturer-specified reamer size, both hemispherical and MIS reamers underream.
Newer reamers cut truer to expected values than used ones. MIS reamers performed
more accurately than hemispherical reamers. Used acetabular reamer systems may
negatively affect the sizing of prepared acetabular beds; therefore, awareness of
this potential inaccuracy should be considered when performing total hip
arthroplasty.
PMID- 28695187
TI - Infection burden in total hip and knee arthroplasties: an international registry
based perspective.
AB - BACKGROUND: Infection remains a leading cause of failure of hip and knee
replacements. Infection burden is the ratio of implants revised for infection to
the total number of arthroplasties in a specific period, measuring the steady
state of infection in a registry. We hypothesized infection burden would be
similar among arthroplasty registries. METHODS: We evaluated publicly reported
data from 6 arthroplasty registries (Australian Orthopaedic Association National
Joint Replacement Registry [AOANJRR], New Zealand Joint Registry, Swedish Hip
Arthroplasty Register, Swedish Knee Arthroplasty Register, National Joint
Registry of England, Wales, Northern Ireland, and the Isle of Man, and the
American Joint Replacement Registry) for revisions performed with an infection
diagnosis over the last 6 years. RESULTS: The 2015 hip infection burden varied
between registries from 0.76% (AOANJRR) to 1.24% (Swedish Hip Arthroplasty
Register), and the unweighted overall average for hip infection burden was 0.97%.
In 2012, 2013, and 2014, average hip infection burden held steady at 0.87%,
0.93%, and 0.94%, respectively, higher than the preceding 2 years. The 2015 knee
infection burden varied from 0.88% (AOANJRR) to 1.28% (Swedish Knee Arthroplasty
Register), and the unweighted average was 1.03%. In 2012, 2013, and 2014, knee
infection burden was 1.04%, 1.11%, and 1.02%, respectively. These numbers were
also higher than the preceding 2 years. CONCLUSIONS: Infection burden may be one
measure of the overall success in registry populations as well as monitoring the
steady state of infection worldwide. Despite global efforts to reduce
postoperative infection, infection burden has actually increased in the selected
registries over time.
PMID- 28695188
TI - Biology of Incidental Catch Sea Star Stellaster childreni Gray, 1840
(Echinodermata: Asteroidea), from Malaysian Borneo Exclusive Economic Zone.
AB - Sea star (class Asteroidea, phylum Echinodermata) is one of the most successful
marine organisms inhabiting a wide range of habitats. As one of the key stone
species, sea stars are responsible for maintaining much of the local diversity of
species within certain communities. Malaysian Exclusive Economic Zone (EEZ)
Resource Survey had been carried out from 16th Aug to 6th Nov 2015 and one of the
invertebrate by-catch organisms is sea star Stellaster childreni Gray, 1840. This
study documents morphological characters and diet of the sea star, besides
providing brief descriptions of the habitats based on particle size analysis and
vessel log data sheet. A total of 217 individuals had been examined throughout
this study. Fragments of flora and fauna were found in the gut including Mollusca
(gastropod, bivalves, and scaphopods), sponge seagrass, and seaweed as well as
benthic Foraminifera. Stellaster childreni were found at depth of 45 m to 185 m
in the South China Sea off Sarawak Malaysia, with various sea bottom substrata.
Approximately 41% of S. childreni were found at a mixture of sandy and muddy
substratum, followed by mixture of sandy and coral (19.3%), muddy substratum
(17.5%), coral substratum (11.5%), and sandy areas (10.6%). The widely
distributed sea star on different types of sea beds suggested healthy deep sea
ecosystem; thus Malaysia should explore further potential fisheries resources in
the EEZ off Sarawak coast.
PMID- 28695189
TI - Risk of Fungal Infection to Dental Patients.
AB - Fungi can cause various diseases, and some pathogenic fungi have been detected in
the water of dental equipment. This environment offers suitable conditions for
fungal biofilms to emerge, which can facilitate mycological contamination. This
study verified whether the water employed in the dental units of two dental
clinics at the University of Franca was contaminated with fungi. This study also
evaluated the ability of the detected fungi to form biofilms. The high-revving
engine contained the largest average amount of fungi, 14.93 +/- 18.18 CFU/mL. The
main fungal species verified in this equipment belonged to the genera Aspergillus
spp., Fusarium spp., Candida spp., and Rhodotorula spp. Among the isolated
filamentous fungi, only one fungus of the genus Fusarium spp. did not form
biofilms. As for yeasts, all the Candida spp. isolates grew as biofilm, but none
of the Rhodotorula spp. isolates demonstrated this ability. Given that
professionals and patients are often exposed to water and aerosols generated by
the dental procedure, the several fungal species detected herein represent a
potential risk especially to immunocompromised patients undergoing dental
treatment. Therefore, frequent microbiological monitoring of the water employed
in dental equipment is crucial to reduce the presence of contaminants.
PMID- 28695190
TI - Relationship between Height-Weight Difference Index and Body-Fat Percentage
Estimated by Bioelectrical Impedance Analysis in Thai Adults.
AB - INTRODUCTION: The height-weight difference index (HWDI) is a new indicator for
evaluating obesity status. While body-fat percentage (BF%) is considered to be
the most accurate obesity evaluation tool, it is a more expensive method and more
difficult to measure than the others. OBJECTIVE: Our objectives were to find the
relationship between HWDI and BF% and to find a BF% prediction model from HWDI in
relation to age and gender. METHOD: Bioelectrical impedance analysis was used to
measure BF% in 2,771 healthy adult Thais. HWDI was calculated as the difference
between height and weight. Pearson's correlation coefficient was used to assess
the relationship between HWDI and BF%. Multiple linear and nonlinear regression
analysis were used to construct the BF% prediction model. RESULTS: HWDI and BF%
were found to be inverse which related to a tendency toward a linear
relationship. Results of a multivariate linear regression analysis, which
included HWDI and age as variables in the model, predicted BF% to be 34.508 -
0.159 (HWDI) + 0.161 (age) for men and 53.35 - 0.265 (HWDI) + 0.132 (age) for
women. CONCLUSIONS: The prediction model provides an easy-to-use obesity
evaluation tool that should help awareness of underweight and obesity conditions.
PMID- 28695191
TI - Simultaneous Determination of Fluoroquinolones and Sulfonamides Originating from
Sewage Sludge Compost.
AB - A simultaneous method for quantitative determination of traces of
fluoroquinolones (FQs) and sulfonamides (SAs) in edible plants fertilized with
sewage sludge was developed. The compounds were extracted from the plants by
rapid and simple liquid extraction followed by extracts clean-up using solid
phase extraction. The eluent additive 1,1,1,3,3,3-hexafluoro-2-propanol was used
for liquid chromatographic detection to achieve separation of structurally
similar antimicrobials like ciprofloxacin and norfloxacin. Identification and
quantification of the compounds were performed using high-performance liquid
chromatography with electrospray ionization mass spectrometry in selected
reaction monitoring mode. Method was validated and extraction recoveries of FQs
and SAs ranged from 66% to 93%. The limit of quantifications was from 5 ng/g in
the case of ofloxacin to 40 ng/g for norfloxacin. The method precision ranged
from 1.43% to 2.61%. The developed novel method was used to evaluate the plats
antimicrobial uptake (potato (Solanum tuberosum L.), carrot (Daucus carota L.),
lettuce (Lactuca sativa L.), and wheat (Triticum vulgare L.)) from soil and
migration of the analytes inside the plants.
PMID- 28695192
TI - Diagnosis and Management of Intraoperative Colorectal Anastomotic Leaks: A Global
Retrospective Patient Chart Review Study.
AB - BACKGROUND: This targeted chart review study reports the first ever detailed
global account of clinical approaches adopted to detect and manage anastomotic
leaks identified during surgery in routine clinical practice. METHOD: 156
surgeons from eight countries retrospectively extracted data from surgical
records of 458 patients who underwent colorectal surgery with an identified
intraoperative leak at the circular anastomosis. Demographic details, procedures,
and outcomes were analyzed descriptively, by country. RESULTS: Most surgeries
were performed laparoscopically (57.6%), followed by open surgeries (35.8%). The
burden of intraoperative leaks on the healthcare system is driven in large part
by the additional interventions such as using a sealant, recreating the
anastomosis, and diverting the anastomosis to a colostomy bag, undertaken to
manage the leak. The mean duration of hospitalization was 19.9 days.
Postoperative anastomotic leaks occurred in 62 patients (13.5%), most frequently
4 to 7 days after surgery. Overall, country-specific differences were observed in
patient characteristics, surgical procedures, method of diagnosis of
intraoperative leak, interventions, and length of hospital stay. CONCLUSION: The
potential cost of time and material needed to repair intraoperative leaks during
surgery is substantial and often hidden to the healthcare system, potentially
leading to an underestimation of the impact of this complication.
PMID- 28695193
TI - Testing for voter rigging in small polling stations.
AB - Nowadays, a large number of countries combine formal democratic institutions with
authoritarian practices. Although in these countries the ruling elites may
receive considerable voter support, they often use several manipulation tools to
control election outcomes. A common practice of these regimes is the coercion and
mobilization of large numbers of voters. This electoral irregularity is known as
voter rigging, distinguishing it from vote rigging, which involves ballot
stuffing or stealing. We develop a statistical test to quantify the extent to
which the results of a particular election display traces of voter rigging. Our
key hypothesis is that small polling stations are more susceptible to voter
rigging because it is easier to identify opposing individuals, there are fewer
eyewitnesses, and interested parties might reasonably expect fewer visits from
election observers. We devise a general statistical method for testing whether
voting behavior in small polling stations is significantly different from the
behavior in their neighbor stations in a way that is consistent with the
widespread occurrence of voter rigging. On the basis of a comparative analysis,
the method enables third parties to conclude that an explanation other than
simple variability is needed to explain geographic heterogeneities in vote
preferences. We analyze 21 elections in 10 countries and find significant
statistical anomalies compatible with voter rigging in Russia from 2007 to 2011,
in Venezuela from 2006 to 2013, and in Uganda in 2011. Particularly disturbing is
the case of Venezuela, where the smallest polling stations were decisive to the
outcome of the 2013 presidential elections.
PMID- 28695194
TI - Topologically enabled optical nanomotors.
AB - Shaping the topology of light, by way of spin or orbital angular momentum
engineering, is a powerful tool to manipulate matter on the nanoscale.
Conventionally, such methods focus on shaping the incident beam of light and not
the full interaction between the light and the object to be manipulated. We
theoretically show that tailoring the topology of the phase space of the light
particle interaction is a fundamentally more versatile approach, enabling
dynamics that may not be achievable by shaping of the light alone. In this
manner, we find that optically asymmetric (Janus) particles can become stable
nanoscale motors even in a light field with zero angular momentum. These
precessing steady states arise from topologically protected anticrossing behavior
of the vortices of the optical torque vector field. Furthermore, by varying the
wavelength of the incident light, we can control the number, orientations, and
the stability of the spinning states. These results show that the combination of
phase-space topology and particle asymmetry can provide a powerful degree of
freedom in designing nanoparticles for optimal external manipulation in a range
of nano-optomechanical applications.
PMID- 28695195
TI - Self-organization of maze-like structures via guided wrinkling.
AB - Sophisticated three-dimensional (3D) structures found in nature are self
organized by bottom-up natural processes. To artificially construct these complex
systems, various bottom-up fabrication methods, designed to transform 2D
structures into 3D structures, have been developed as alternatives to
conventional top-down lithography processes. We present a different self
organization approach, where we construct microstructures with periodic and
ordered, but with random architecture, like mazes. For this purpose, we
transformed planar surfaces using wrinkling to directly use randomly generated
ridges as maze walls. Highly regular maze structures, consisting of several
tessellations with customized designs, were fabricated by precisely controlling
wrinkling with the ridge-guiding structure, analogous to the creases in origami.
The method presented here could have widespread applications in various material
systems with multiple length scales.
PMID- 28695196
TI - Multiple structural transitions driven by spin-phonon couplings in a perovskite
oxide.
AB - Spin-phonon interactions are central to many interesting phenomena, ranging from
superconductivity to magnetoelectric effects. However, they are believed to have
a negligible influence on the structural behavior of most materials. For example,
magnetic perovskite oxides often undergo structural transitions accompanied by
magnetic signatures whose minuteness suggests that the underlying spin-phonon
couplings are largely irrelevant. We present an exception to this rule, showing
that novel effects can occur as a consequence. Our first-principles calculations
reveal that spin-phonon interactions are essential to reproduce the experimental
observations on the phase diagram of magnetoelectric multiferroic BiCoO3.
Moreover, we predict that, under compression, these couplings lead to an
unprecedented temperature-driven double-reentrant sequence of ferroelectric
transitions. We propose how to modify BiCoO3 via chemical doping to reproduce
such marked effects under ambient conditions, thereby yielding useful
multifunctionality.
PMID- 28695197
TI - Ferroelectric polarization induces electronic nonlinearity in ion-doped
conducting polymers.
AB - Poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) is an organic
mixed ion-electron conducting polymer. The PEDOT phase transports holes and is
redox-active, whereas the PSS phase transports ions. When PEDOT is redox-switched
between its semiconducting and conducting state, the electronic and optical
properties of its bulk are controlled. Therefore, it is appealing to use this
transition in electrochemical devices and to integrate those into large-scale
circuits, such as display or memory matrices. Addressability and memory
functionality of individual devices, within these matrices, are typically
achieved by nonlinear current-voltage characteristics and bistability-functions
that can potentially be offered by the semiconductor-conductor transition of
redox polymers. However, low conductivity of the semiconducting state and poor
bistability, due to self-discharge, make fast operation and memory retention
impossible. We report that a ferroelectric polymer layer, coated along the
counter electrode, can control the redox state of PEDOT. The polarization
switching characteristics of the ferroelectric polymer, which take place as the
coercive field is overcome, introduce desired nonlinearity and bistability in
devices that maintain PEDOT in its highly conducting and fast-operating regime.
Memory functionality and addressability are demonstrated in ferro-electrochromic
display pixels and ferro-electrochemical transistors.
PMID- 28695198
TI - Neat monolayer tiling of molecularly thin two-dimensional materials in 1 min.
AB - Controlled arrangement of molecularly thin two-dimensional (2D) materials on a
substrate, particularly into precisely organized mono- and multilayer structures,
is a key to design a nanodevice using their unique and enhanced physical
properties. Several techniques such as mechanical transfer process and Langmuir
Blodgett deposition have been applied for this purpose, but they have severe
restrictions for large-scale practical applications, for example, limited
processable area and long fabrication time, requiring skilled multistep
operations. We report a facile one-pot spin-coating method to realize dense
monolayer tiling of various 2D materials, such as graphene and metal oxide
nanosheets, within 1 min over a wide area (for example, a 30-mmphi substrate).
Centrifugal force drives the nanosheets in a thin fluid layer to the substrate
edge where they are packed edge to edge all the way to the central region,
without forming overlaps. We investigated the relationship between precursor
concentration, rotation speed, and ultraviolet-visible absorbance and developed
an effective method to optimize the parameters for neat monolayer films. The
multilayer buildup is feasible by repeating the spin-coating process combined
with a heat treatment at moderate temperature. This versatile solution-based
technique will provide both fundamental and practical advancements in the rapid
large-scale production of artificial lattice-like films and nanodevices based on
2D materials.
PMID- 28695199
TI - A selective electrocatalyst-based direct methanol fuel cell operated at high
concentrations of methanol.
AB - Owing to the serious crossover of methanol from the anode to the cathode through
the polymer electrolyte membrane, direct methanol fuel cells (DMFCs) usually use
dilute methanol solutions as fuel. However, the use of high-concentration
methanol is highly demanded to improve the energy density of a DMFC system.
Instead of the conventional strategies (for example, improving the fuel-feed
system, membrane development, modification of electrode, and water management),
we demonstrate the use of selective electrocatalysts to run a DMFC at high
concentrations of methanol. In particular, at an operating temperature of 80
degrees C, the as-fabricated DMFC with core-shell-shell Au@Ag2S@Pt nanocomposites
at the anode and core-shell Au@Pd nanoparticles at the cathode produces a maximum
power density of 89.7 mW cm-2 at a methanol feed concentration of 10 M and
maintains good performance at a methanol concentration of up to 15 M. The high
selectivity of the electrocatalysts achieved through structural construction
accounts for the successful operation of the DMFC at high concentrations of
methanol.
PMID- 28695200
TI - Room temperature high-detectivity mid-infrared photodetectors based on black
arsenic phosphorus.
AB - The mid-infrared (MIR) spectral range, pertaining to important applications, such
as molecular "fingerprint" imaging, remote sensing, free space telecommunication,
and optical radar, is of particular scientific interest and technological
importance. However, state-of-the-art materials for MIR detection are limited by
intrinsic noise and inconvenient fabrication processes, resulting in high-cost
photodetectors requiring cryogenic operation. We report black arsenic phosphorus
based long-wavelength IR photodetectors, with room temperature operation up to
8.2 MUm, entering the second MIR atmospheric transmission window. Combined with a
van der Waals heterojunction, room temperature-specific detectivity higher than
4.9 * 109 Jones was obtained in the 3- to 5-MUm range. The photodetector works in
a zero-bias photovoltaic mode, enabling fast photoresponse and low dark noise.
Our van der Waals heterojunction photodetectors not only exemplify black arsenic
phosphorus as a promising candidate for MIR optoelectronic applications but also
pave the way for a general strategy to suppress 1/f noise in photonic devices.
PMID- 28695201
TI - Templated deprotonative metalation of polyaryl systems: Facile access to simple,
previously inaccessible multi-iodoarenes.
AB - The development of new methodologies to affect non-ortho-functionalization of
arenes has emerged as a globally important arena for research, which is key to
both fundamental studies and applied technologies. A range of simple arene
feedstocks (namely, biphenyl, meta-terphenyl, para-terphenyl, 1,3,5
triphenylbenzene, and biphenylene) is transformed to hitherto unobtainable multi
iodoarenes via an s-block metal sodium magnesiate templated deprotonative
approach. These iodoarenes have the potential to be used in a whole host of high
impact transformations, as precursors to key materials in the pharmaceutical,
molecular electronic, and nanomaterials industries. To prove the concept, we
transformed biphenyl to 3,5-bis(N-carbazolyl)-1,1'-biphenyl, a novel isomer of
4,4'-bis(N-carbazolyl)-1,1'-biphenyl (CPB), a compound which is currently widely
used as a host material for organic light-emitting diodes.
PMID- 28695202
TI - Single-crystalline germanium nanomembrane photodetectors on foreign nanocavities.
AB - Miniaturization of optoelectronic devices offers tremendous performance gain. As
the volume of photoactive material decreases, optoelectronic performance
improves, including the operation speed, the signal-to-noise ratio, and the
internal quantum efficiency. Over the past decades, researchers have managed to
reduce the volume of photoactive materials in solar cells and photodetectors by
orders of magnitude. However, two issues arise when one continues to thin down
the photoactive layers to the nanometer scale (for example, <50 nm). First, light
matter interaction becomes weak, resulting in incomplete photon absorption and
low quantum efficiency. Second, it is difficult to obtain ultrathin materials
with single-crystalline quality. We introduce a method to overcome these two
challenges simultaneously. It uses conventional bulk semiconductor wafers, such
as Si, Ge, and GaAs, to realize single-crystalline films on foreign substrates
that are designed for enhanced light-matter interaction. We use a high-yield and
high-throughput method to demonstrate nanometer-thin photodetectors with
significantly enhanced light absorption based on nanocavity interference
mechanism. These single-crystalline nanomembrane photodetectors also exhibit
unique optoelectronic properties, such as the strong field effect and spectral
selectivity.
PMID- 28695203
TI - Slow climate mode reconciles historical and model-based estimates of climate
sensitivity.
AB - The latest Intergovernmental Panel on Climate Change Assessment Report widened
the equilibrium climate sensitivity (ECS) range from 2 degrees to 4.5 degrees C
to an updated range of 1.5 degrees to 4.5 degrees C in order to account for the
lack of consensus between estimates based on models and historical observations.
The historical ECS estimates range from 1.5 degrees to 3 degrees C and are
derived assuming a linear radiative response to warming. A Bayesian methodology
applied to 24 models, however, documents curvature in the radiative response to
warming from an evolving contribution of interannual to centennial modes of
radiative response. Centennial modes display stronger amplifying feedbacks and
ultimately contribute 28 to 68% (90% credible interval) of equilibrium warming,
yet they comprise only 1 to 7% of current warming. Accounting for these
unresolved centennial contributions brings historical records into agreement with
model-derived ECS estimates.
PMID- 28695204
TI - Resolving quanta of collective spin excitations in a millimeter-sized
ferromagnet.
AB - Combining different physical systems in hybrid quantum circuits opens up novel
possibilities for quantum technologies. In quantum magnonics, quanta of
collective excitation modes in a ferromagnet, called magnons, interact coherently
with qubits to access quantum phenomena of magnonics. We use this architecture to
probe the quanta of collective spin excitations in a millimeter-sized
ferromagnetic crystal. More specifically, we resolve magnon number states through
spectroscopic measurements of a superconducting qubit with the hybrid system in
the strong dispersive regime. This enables us to detect a change in the magnetic
moment of the ferromagnet equivalent to a single spin flipped among more than
1019 spins. Our demonstration highlights the strength of hybrid quantum systems
to provide powerful tools for quantum sensing and quantum information processing.
PMID- 28695205
TI - Revisiting ancestral polyploidy in plants.
AB - Whole-genome duplications (WGDs) or polyploidy events have been studied
extensively in plants. In a now widely cited paper, Jiao et al. presented
evidence for two ancient, ancestral plant WGDs predating the origin of flowering
and seed plants, respectively. This finding was based primarily on a bimodal age
distribution of gene duplication events obtained from molecular dating of almost
800 phylogenetic gene trees. We reanalyzed the phylogenomic data of Jiao et al.
and found that the strong bimodality of the age distribution may be the result of
technical and methodological issues and may hence not be a "true" signal of two
WGD events. By using a state-of-the-art molecular dating algorithm, we
demonstrate that the reported bimodal age distribution is not robust and should
be interpreted with caution. Thus, there exists little evidence for two ancient
WGDs in plants from phylogenomic dating.
PMID- 28695206
TI - A fourth Denisovan individual.
AB - The presence of Neandertals in Europe and Western Eurasia before the arrival of
anatomically modern humans is well supported by archaeological and
paleontological data. In contrast, fossil evidence for Denisovans, a sister group
of Neandertals recently identified on the basis of DNA sequences, is limited to
three specimens, all of which originate from Denisova Cave in the Altai Mountains
(Siberia, Russia). We report the retrieval of DNA from a deciduous lower second
molar (Denisova 2), discovered in a deep stratigraphic layer in Denisova Cave,
and show that this tooth comes from a female Denisovan individual. On the basis
of the number of "missing substitutions" in the mitochondrial DNA determined from
the specimen, we find that Denisova 2 is substantially older than two of the
other Denisovans, reinforcing the view that Denisovans were likely to have been
present in the vicinity of Denisova Cave over an extended time period. We show
that the level of nuclear DNA sequence diversity found among Denisovans is within
the lower range of that of present-day human populations.
PMID- 28695207
TI - Peripheral myelin protein 22 alters membrane architecture.
AB - Peripheral myelin protein 22 (PMP22) is highly expressed in myelinating Schwann
cells of the peripheral nervous system. PMP22 genetic alterations cause the most
common forms of Charcot-Marie-Tooth disease (CMTD), which is characterized by
severe dysmyelination in the peripheral nerves. However, the functions of PMP22
in Schwann cell membranes remain unclear. We demonstrate that reconstitution of
purified PMP22 into lipid vesicles results in the formation of compressed and
cylindrically wrapped protein-lipid vesicles that share common organizational
traits with compact myelin of peripheral nerves in vivo. The formation of these
myelin-like assemblies depends on the lipid-to-PMP22 ratio, as well as on the
PMP22 extracellular loops. Formation of the myelin-like assemblies is disrupted
by a CMTD-causing mutation. This study provides both a biochemical assay for
PMP22 function and evidence that PMP22 directly contributes to membrane
organization in compact myelin.
PMID- 28695209
TI - Comment on "Monkey vocal tracts are speech-ready".
AB - Monkey vocal tracts are capable of producing monkey speech, not the full range of
articulate human speech. The evolution of human speech entailed both anatomy and
brains. Fitch, de Boer, Mathur, and Ghazanfar in Science Advances claim that
"monkey vocal tracts are speech-ready," and conclude that "...the evolution of
human speech capabilities required neural change rather than modifications of
vocal anatomy." Neither premise is consistent either with the data presented and
the conclusions reached by de Boer and Fitch themselves in their own published
papers on the role of anatomy in the evolution of human speech or with the body
of independent studies published since the 1950s.
PMID- 28695208
TI - Population genomics of picophytoplankton unveils novel chromosome
hypervariability.
AB - Tiny photosynthetic microorganisms that form the picoplankton (between 0.3 and 3
MUm in diameter) are at the base of the food web in many marine ecosystems, and
their adaptability to environmental change hinges on standing genetic variation.
Although the genomic and phenotypic diversity of the bacterial component of the
oceans has been intensively studied, little is known about the genomic and
phenotypic diversity within each of the diverse eukaryotic species present. We
report the level of genomic diversity in a natural population of Ostreococcus
tauri (Chlorophyta, Mamiellophyceae), the smallest photosynthetic eukaryote.
Contrary to the expectations of clonal evolution or cryptic species, the spectrum
of genomic polymorphism observed suggests a large panmictic population (an
effective population size of 1.2 * 107) with pervasive evidence of sexual
reproduction. De novo assemblies of low-coverage chromosomes reveal two large
candidate mating-type loci with suppressed recombination, whose origin may pre
date the speciation events in the class Mamiellophyceae. This high genetic
diversity is associated with large phenotypic differences between strains.
Strikingly, resistance of isolates to large double-stranded DNA viruses, which
abound in their natural environment, is positively correlated with the size of a
single hypervariable chromosome, which contains 44 to 156 kb of strain-specific
sequences. Our findings highlight the role of viruses in shaping genome diversity
in marine picoeukaryotes.
PMID- 28695210
TI - Detection of a dynamic topography signal in last interglacial sea-level records.
AB - Estimating minimum ice volume during the last interglacial based on local sea
level indicators requires that these indicators are corrected for processes that
alter local sea level relative to the global average. Although glacial isostatic
adjustment is generally accounted for, global scale dynamic changes in topography
driven by convective mantle flow are generally not considered. We use numerical
models of mantle flow to quantify vertical deflections caused by dynamic
topography and compare predictions at passive margins to a globally distributed
set of last interglacial sea-level markers. The deflections predicted as a result
of dynamic topography are significantly correlated with marker elevations (>95%
probability) and are consistent with construction and preservation attributes
across marker types. We conclude that a dynamic topography signal is present in
the elevation of last interglacial sea-level records and that the signal must be
accounted for in any effort to determine peak global mean sea level during the
last interglacial to within an accuracy of several meters.
PMID- 28695211
TI - Solving protein structures using short-distance cross-linking constraints as a
guide for discrete molecular dynamics simulations.
AB - We present an integrated experimental and computational approach for de novo
protein structure determination in which short-distance cross-linking data are
incorporated into rapid discrete molecular dynamics (DMD) simulations as
constraints, reducing the conformational space and achieving the correct protein
folding on practical time scales. We tested our approach on myoglobin and FK506
binding protein-models for alpha helix-rich and beta sheet-rich proteins,
respectively-and found that the lowest-energy structures obtained were in
agreement with the crystal structure, hydrogen-deuterium exchange, surface
modification, and long-distance cross-linking validation data. Our approach is
readily applicable to other proteins with unknown structures.
PMID- 28695212
TI - A tail of two voltages: Proteomic comparison of the three electric organs of the
electric eel.
AB - The electric eel (Electrophorus electricus) is unusual among electric fishes
because it has three pairs of electric organs that serve multiple biological
functions: For navigation and communication, it emits continuous pulses of weak
electric discharge (<1 V), but for predation and defense, it intermittently emits
lethal strong electric discharges (10 to 600 V). We hypothesized that these two
electrogenic outputs have different energetic demands reflected by differences in
their proteome and phosphoproteome. We report the use of isotope-assisted
quantitative mass spectrometry to test this hypothesis. We observed novel
phosphorylation sites in sodium transporters and identified a potassium channel
with unique differences in protein concentration among the electric organs. In
addition, we found transcription factors and protein kinases that show
differential abundance in the strong versus weak electric organs. Our findings
support the hypothesis that proteomic differences among electric organs underlie
differences in energetic needs, reflecting a trade-off between generating weak
voltages continuously and strong voltages intermittently.
PMID- 28695213
TI - Extracellular polymeric substances are transient media for microbial
extracellular electron transfer.
AB - Microorganisms exploit extracellular electron transfer (EET) in growth and
information exchange with external environments or with other cells. Every
microbial cell is surrounded by extracellular polymeric substances (EPS).
Understanding the roles of three-dimensional (3D) EPS in EET is essential in
microbiology and microbial exploitation for mineral bio-respiration, pollutant
conversion, and bioenergy production. We have addressed these challenges by
comparing pure and EPS-depleted samples of three representative electrochemically
active strains viz Gram-negative Shewanella oneidensis MR-1, Gram-positive
Bacillus sp. WS-XY1, and yeast Pichia stipites using technology from
electrochemistry, spectroscopy, atomic force microscopy, and microbiology.
Voltammetry discloses redox signals from cytochromes and flavins in intact MR-1
cells, whereas stronger signals from cytochromes and additional signals from both
flavins and cytochromes are found after EPS depletion. Flow cytometry and
fluorescence microscopy substantiated by N-acetylglucosamine and electron
transport system activity data showed less than 1.5% cell damage after EPS
extraction. The electrochemical differences between normal and EPS-depleted cells
therefore originate from electrochemical species in cell walls and EPS. The 35 +/
15-nm MR-1 EPS layer is also electrochemically active itself, with cytochrome
electron transfer rate constants of 0.026 and 0.056 s-1 for intact MR-1 and EPS
depleted cells, respectively. This surprisingly small rate difference suggests
that molecular redox species at the core of EPS assist EET. The combination of
all the data with electron transfer analysis suggests that electron "hopping" is
the most likely molecular mechanism for electrochemical electron transfer through
EPS.
PMID- 28695214
TI - Response to Lieberman on "Monkey vocal tracts are speech-ready".
AB - Macaques do have a speech-ready vocal tract, but lack a speech-ready brain to
control it.
PMID- 28695215
TI - Characterisation of a stably integrated expression system for exogenous protein
expression in DT40.
AB - The use of constitutive promoters to drive exogenous protein expression is an
important tool for the study of diverse biological processes. To create and
characterise a stably integrated expression system for DT40 cells, we constructed
integration cassettes for three commonly used promoter elements; CMV, CBA or CAG,
and used these to stably integrate a TOPBP1 transgene at the OVA locus, a
transcriptionally silent locus commonly used in DT40. We next performed a
comparative analysis of protein expression levels and identified CAG as the most
efficient of the promoter elements we have tested in DT40 cells. To assess
whether the site of integration affected the levels of transgene expression, a
second chromosomal locus, immediately adjacent to the endogenous TOPBP1 gene, was
tested for CAG. No major differences in TopBP1 overexpression were observed. This
confirms that use of the OVA locus for integrating transgenes is a rational
choice for DT40. Finally, we demonstrate that our stably integrated
overexpression system (SIOS) constructs can be efficiently excised by the
induction of tamoxifen-regulated Cre expression. Taken together, SIOS is an easy
to-use and versatile system for constitutive, reversible exogenous protein
production that provides a range of potential expression levels. This will be a
useful experimental tool for future DT40 experiments.
PMID- 28695217
TI - DEATH AND THE MEDIA: INFECTIOUS DISEASE REPORTING DURING THE HEALTH TRANSITION.
AB - In the late 19th Century, cities in Western Europe and the United States suffered
from high levels of infectious disease. Over a 40 year period, there was a
dramatic decline in infectious disease deaths in cities. As such objective
progress in urban quality of life took place, how did the media report this
trend? At that time newspapers were the major source of information educating
urban households about the risks they faced. By constructing a unique panel data
base, we find that news reports were positively associated with government
announced typhoid mortality counts and the size of this effect actually grew
after the local governments made large investments in public water works to
reduce typhoid rates. News coverage was more responsive to unexpected increases
in death rates than to unexpected decreases in death rates.
PMID- 28695216
TI - From perception to action in songbird production: dynamics of a whole loop.
AB - Birdsong emerges when a set of highly interconnected brain areas manage to
generate a complex output. This consists of precise respiratory rhythms as well
as motor instructions to control the vocal organ configuration. In this way,
during birdsong production, dedicated cortical areas interact with life
supporting ones in the brainstem, such as the respiratory nuclei. We discuss an
integrative view of this interaction together with a widely accepted "top-down"
representation of the song system. We also show that a description of this neural
network in terms of dynamical systems allows to explore songbird production and
processing by generating testable predictions.
PMID- 28695218
TI - Determination of the nano-scaled contact area of staphylococcal cells.
AB - Bacterial adhesion is a crucial step during the development of infections as well
as the formation of biofilms. Hence, fundamental research of bacterial adhesion
mechanisms is of utmost importance. So far, less is known about the size of the
contact area between bacterial cells and a surface. This gap will be filled by
this study using a single-cell force spectroscopy-based method to investigate the
contact area between a single bacterial cell of Staphylococcus aureus and a solid
substrate. The technique relies on the strong influence of the hydrophobic
interaction on bacterial adhesion: by incrementally crossing a very sharp
hydrophobic/hydrophilic interface while performing force-distance curves with a
single bacterial probe, the bacterial contact area can be determined. Assuming
circular contact areas, their radii - determined in our experiments - are in the
range from tens of nanometers to a few hundred nanometers. The contact area can
be slightly enlarged by a larger load force, yet does not resemble a Hertzian
contact, rather, the enlargement is a property of the individual bacterial cell.
Additionally, Staphylococcus carnosus has been probed, which is less adherent
than S. aureus, yet both bacteria exhibit a similar contact area size. This
corroborates the notion that the adhesive strength of bacteria is not a matter of
contact area, but rather a matter of which and how many molecules of the
bacterial species' cell wall form the contact. Moreover, our method of
determining the contact area can be applied to other microorganisms and the
results might also be useful for studies using nanoparticles covered with soft,
macromolecular coatings.
PMID- 28695219
TI - Highly efficient chemoenzymatic synthesis and facile purification of alpha-Gal
pentasaccharyl ceramide Galalpha3nLc4betaCer.
AB - A highly efficient chemoenzymatic method for synthesizing glycosphingolipids
using alpha-Gal pentasaccharyl ceramide as an example is reported here. Enzymatic
extension of the chemically synthesized lactosyl sphingosine using efficient
sequential one-pot multienzyme (OPME) reactions allowed glycosylation to be
carried out in aqueous solutions. Facile C18 cartridge-based quick (<30 minutes)
purification protocols were established using minimal amounts of green solvents
(CH3CN and H2O). Simple acylation in the last step led to the formation of the
target glycosyl ceramide in 4 steps with an overall yield of 57%.
PMID- 28695220
TI - Chain-breaking antioxidant activity of hydroxylated and methoxylated magnolol
derivatives: the role of H-bonds.
AB - Chemical modification of magnolol, an uncommon dimeric neolignan contained in
Magnolia genus trees, provides a unique array of polyphenols having interesting
biological activity potentially related to radical scavenging. The chain-breaking
antioxidant activity of four new hydroxylated and methoxylated magnolol
derivatives was explored by experimental and computational methods. The
measurement of the rate constant of the reaction with ROO radicals (kinh) in an
apolar solvent showed that the introduction of hydroxyl groups ortho to the
phenolic OH in magnolol increased the kinh value, being 2.4 * 105 M-1 s-1 and 3.3
* 105 M-1 s-1 for the mono and the dihydroxy derivatives respectively (kinh of
magnolol is 6.1 * 104 M-1 s-1). The di-methoxylated derivative is less reactive
than magnolol (kinh = 1.1 * 104 M-1 s-1), while the insertion of both hydroxyl
and methoxyl groups showed no effect (6.0 * 104 M-1 s-1). Infrared spectroscopy
and theoretical calculations allowed a rationalization of these results and
pointed out the crucial role of intramolecular H-bonds. We also show that a
correct estimation of the rate constant of the reaction with ROO radicals, by
using BDE(OH) calculations, requires that the geometry of the radical is as close
as possible to that of the parent phenol.
PMID- 28695221
TI - Core-shell nano-latex blending method to prepare multi-shape memory polymers.
AB - Multi-shape memory polymers were prepared by blending a series of styrene (St)
block-(styrene-random-meth acrylate (MA))-block-styrene triblock copolymer nano
latexes. These latexes synthesized using a reversible addition-fragmentation
chain transfer (RAFT) emulsion polymerization method have a core-shell structure.
The cores are formed by the middle poly(St-random-MA) blocks. They act as
transition phases with variable transition temperatures via adjusting the St/MA
ratio. When the latexes are blended with an identical PSt shell but different
poly(St-random-MA) cores, the shells play a role in preventing the aggregation of
these poly(St-random-MA) cores forming a crosslinked network after hot-press
treatment. Therefore a polymer with well-distributed multiple nanophases is
achieved, which shows a quadruple-shape memory behavior. Furthermore, the shape
memory and recovery performance at a certain temperature can be improved on
purpose by increasing the mass ratio of the corresponding transition phases,
which can be realized via simply varying the blending ratio of different latexes.
An optimized multi-shape memory polymer with the shape memory and recovery ratio
higher than 80% at all the transition temperatures is achieved.
PMID- 28695222
TI - Ratiometric in vivo auditioning of targeted silver nanoparticles.
AB - Attaching affinity ligands to nanoparticles (NPs) increases selectivity for
targeting cells and tissues, and can result in improved sensitivity and reduced
off-target toxicity in diagnostic and therapeutic systems. The decision over key
features - NP size, shape, coating strategies and targeting ligands for clinical
translation is often hampered by a lack of quantitative in vivo NP homing assays.
Sensitive, internally controlled assays are needed which allow for quantitative
comparisons (auditions) among various formulations of targeted NPs. We recently
reported the development of peptide-functionalized, isotopically-barcoded silver
NPs (AgNPs) for ultrasensitive studies centered on measuring relative ratios of
NP internalization into cultured cells. Here we evaluated the application of this
technology for NP homing studies in live mice using peptides with previously
described tissue tropism; one peptide that favors vascular beds of the normal
lungs (RPARPAR; receptor neuropilin-1, or NRP-1) and another that is selective
for central nervous system vessels (CAGALCY). Equimolar mixtures of the peptide
targeted Ag107-NPs and Ag109 control particles were mixed and injected
intravenously. Distribution profiles of Ag107 and Ag109 in tissue extracts were
determined simultaneously through inductively coupled plasma mass spectrometry
(ICP-MS). Compared to non-targeted particles up to ~9-fold increased lung
accumulation was seen for RPARPAR-OH AgNPs (but not for AgNPs functionalized with
RPARPAR-NH2, which does not bind to NRP-1). Similarly, AgNPs functionalized with
the brain-homing CAGALCY peptide were overrepresented in brain extracts. Spatial
distribution (mapping) analysis by laser ablation ICP-MS (LA-ICP-MS) was used to
determine the ratio Ag107/Ag109 in tissue cryosections. The mapping demonstrated
preferential accumulation of the RPARPAR-AgNPs in the perivascular areas around
pulmonary veins, and CAGALCY AgNPs accumulated in discrete areas of the brain
(e.g. in the vessels of cerebellar fibrillary tracts). Based on these results,
the internally controlled ratiometric AgNP system is suitable for quantitative
studies of the effect of targeting ligands on NP biodistribution, at average
tissue concentration and distribution at the microscopic level. The platform
might be particularly relevant for target sites with high local variability in
uptake, such as tumors.
PMID- 28695223
TI - A Journey in Science: Cell-Cycle Control.
AB - Real innovations in medicine and science are historic and singular; the stories
behind each occurrence are precious. At Molecular Medicine we have established
the Anthony Cerami Award in Translational Medicine to document and preserve these
histories. The monographs recount the seminal events as told in the voice of the
original investigators who provided the crucial early insight. These essays
capture the essence of discovery, chronicling the birth of ideas that created new
fields of research; and launched trajectories that persisted and ultimately
influenced how disease is prevented, diagnosed, and treated. In this volume, the
Cerami Award Monograph is by Paul Nurse, Director, The Francis Crick Institute in
London, UK. A visionary in the field of cell biology, this is the story of Dr.
Nurse's scientific journey.
PMID- 28695224
TI - [Pathologic results after laparoscopic and open surgery for rectal cancer].
PMID- 28695225
TI - [Transanal total mesorectal excision (TaTME) for primary rectal cancer : Video
article].
AB - Transanal total mesorectal excision (TaTME) is a new surgical technique in the
treatment of selected patients with rectal cancer. This manuscript and the
accompanying video report with commentary, which is available online, outlines
various equipment requirements and step by step aspects of the surgical
technique. With respect to the implementation of TaTME particular attention
should be paid to the topography and surgical education.
PMID- 28695227
TI - [Cancellous screws versus dynamic hip screw fixation of femural neck fractures :
The Fixation using Alternative Implants for the Treatment of Hip fractures Study
(FAITH)].
PMID- 28695226
TI - Fenretinide differentially modulates the levels of long- and very long-chain
ceramides by downregulating Cers5 enzyme: evidence from bench to bedside.
AB - : Cystic fibrosis is the most common genetic disease, in which symptoms may be
alleviated but not fully eliminated. Ceramides have long been implicated in the
inflammatory etiology of cystic fibrosis, with contradicting reports with regards
to their role. Recently, significant biological and biophysical differences have
been observed between long- and very long-chain ceramides. This work reveals that
long-chain ceramides are upregulated whereas very long-chain ceramides are
downregulated in cell lines, mouse animal model, and patients with cystic
fibrosis, compared with their controls. Treatment with fenretinide decreases the
levels of long-chain ceramides and increases the levels of very long-chain
ceramides. Our results show that restoration of cystic fibrosis conductance
regulator (CFTR) expression is associated with normalization of aberrant levels
of specific ceramides. This demonstrates for the first time a correlation between
CFTR protein expression and regulation of specific ceramide levels. Furthermore,
using cystic fibrosis lung epithelial cell lines, we demonstrate that this effect
can be attributed to the transcriptional downregulation of ceramide synthase 5
(Cers5) enzyme. We also discovered a partial synergism between fenretinide and
zinc (Zn2+), which deficiency has been reported in patients with cystic fibrosis.
Overall, in addition to having direct translational application, we believe that
our findings contribute to the understanding of ceramide metabolism in cystic
fibrosis, as well as other inflammatory diseases where imbalances of ceramides
have also been observed. KEY MESSAGES: Long- and very long-chain ceramides (LCCs
and VLCCs) are biochemically distinct. LCCs are upregulated whereas VLCCs are
downregulated in cystic fibrosis. Fenretinide downregulates the levels of LCCs
and upregulates the levels of VLCCs. Fenretinide changes the balance of LCCs and
VLCCs by downregulating Cers5 enzyme. Fenretinide and zinc ions cooperate in the
modulation of ceramide levels.
PMID- 28695228
TI - "Tumor immunology meets oncology (TIMO) XII", April 28th-30th 2016, Halle/Saale,
Germany.
PMID- 28695229
TI - Application of the entomogenous fungus, Metarhizium anisopliae, for leafroller
(Cnaphalocrocis medinalis) control and its effect on rice phyllosphere microbial
diversity.
AB - Microbial pesticides form critical components of integrated pest management (IPM)
practices. Little, however, is known regarding the impacts of these organisms on
the indigenous microbial community. We show that Metarhizium anisopliae strain
CQMa421 was highly effective in controlling the rice leafroller, Cnaphalocrocis
medinalis Guenee. In addition, M. anisopliae distribution and its effects on
phyllosphere microbial diversity after application in field trials were
investigated. Phylloplane specific distribution of the fungus was observed over
time, with more rapid declines of M. anisopliae CFUs (colony-forming units) seen
in the top leaf layer as compared to lower layers. Application of the fungus
resulted in transient changes in the endogenous microbial diversity with
variations seen in the bacterial observed species and Shannon index. Notable
increases in both parameters were seen at 6-day post-application of M.
anisopliae, although significant variation within sample replicates for bacteria
and fungi were noted. Application of M. anisopliae increased the relative
distribution of bacterial species implicated in plant growth promotion and
organic pollutant degradation, e.g., Methylobacterium, Sphingobium, and
Deinococcus. These data show minimal impact of M. anisopliae on endogenous
microbial diversity with transient changes in bacterial abundance/diversity that
may result in added benefits to crops.
PMID- 28695230
TI - Screening for proteolytically active lactic acid bacteria and bioactivity of
peptide hydrolysates obtained with selected strains.
AB - In a screening for proteolytically active lactic acid bacteria, three strains,
Lactobacillus delbrueckii ssp. lactis 92202, Lactobacillus helveticus 92201, and
Lactobacillus delbrueckii ssp. bulgaricus 92059, showed the highest activities
following growth in milk. All three strains degraded alpha- and beta-casein, but
did not hydrolyse kappa-casein. HPLC analysis of skim milk fermentation revealed
increasing amounts of peptides after 5 and 10 h with Lb. d. ssp. bulgaricus
92059. Hydrolysates obtained with Lb. d. ssp. lactis 92202 and Lb. d. ssp.
bulgaricus 92059 revealed the highest angiotensin-converting enzyme-inhibitory
effect. The effect was dose dependent. Almost no effect (<10%) was seen for Lb.
helveticus 92201. For Lb. d. ssp. bulgaricus 92059, maximal inhibition of approx.
65% was reached after 25 h of fermentation. In an in vitro assay measuring
potential immunomodulation, hydrolysates of the three strains yielded anti
inflammatory activities in the presence of TNF-alpha. However, the effects were
more pronounced at lower hydrolysate concentrations. In the absence of TNF-alpha,
slight pro-inflammatory effects were observed. The hydrolysate of Lb. d. ssp.
bulgaricus 92059, when purified by means of solid-phase extraction, exhibited pro
inflammatory activity. Sour whey containing Lb. d. ssp. bulgaricus 92059 cells
showed pro-inflammatory activity while cell-free sour whey was clearly anti
inflammatory. In the purified hydrolysate, 20 different alpha- and beta-casein
(CN)-derived peptides could be identified by LC-MS. Most peptides originated from
the central and C-terminal regions of beta-casein. Peptide length was between 9
(beta-CN(f 59-67)) and 22 amino acids (beta-CN(f 117-138)).
PMID- 28695231
TI - Erratum to: Role of the aryl hydrocarbon receptor in carcinogenesis and potential
as an anti-cancer drug target.
PMID- 28695232
TI - Resolving the chemical structures of off-odorants and potentially harmful
substances in toys-example of children's swords.
AB - Most children's toys on the market are primarily made out of plastic and other
complex composite materials. Consumer complaints about offensive odors or
irritating effects associated with toy products have increased in recent years.
One example is the strongly perceivable negative odor reported for a particular
series of toy swords. Characterizing the presence of contaminants, including
those that have the potential to be deleterious to health, in such products is a
significant analytical challenge due to the high baseline abundance of chemical
constituents of the materials used in the products. In the present study, the
nature of offensive odorants associated with toy sword products was examined by
gas chromatography (GC). After initial sensory evaluations, the volatile
compounds from the toy products were recovered using solvent extraction and
solvent-assisted flavor evaporation. The extracts were analyzed using GC
olfactometry (GC-O) and two-dimensional GC-O coupled with mass spectrometry (GC
GC-MS/O). A total of 26 odor-active compounds, including aromatic hydrocarbons
and phenols, were identified among numerous non-odorous volatile by-products.
These substances also included polycyclic aromatic hydrocarbons, which were
analyzed by GC-MS. Representative substances were naphthalene and 1,2
dihydronaphthalene that exhibited moldy, mothball-like odor impressions, and
phenol derivatives with leather-like, phenolic, horse-stable-like smells. The
odorants detected correlated with the assigned attributes from the sensory
analyses. This study clearly shows that the detection and identification of such
odorous contaminants can provide key indications of potentially harmful yet
unknown substances in everyday products such as toys. Graphical abstract ?.
PMID- 28695233
TI - LI-RADS(r) algorithm: CT and MRI.
AB - The Liver Imaging Reporting and Data System (LI-RADS(r)) is an imaging-based
diagnostic system applicable in patients at high risk of hepatocellular carcinoma
(HCC). In LI-RADS, each liver observation is assigned a category that reflects
probability of benignity, HCC, or other malignancy. Familiarity with the LI-RADS
diagnostic algorithm is necessary to appropriately implement LI-RADS in clinical
practice. This review discusses steps necessary for application of the LI-RADS
algorithm and provides examples illustrating each step.
PMID- 28695234
TI - Pre- and neonatal imaging of gastrointestinal complications in congenital
diaphragmatic hernia.
AB - The initial outcome in infants with congenital diaphragmatic hernia is mainly
related to the associated lung hypoplasia. However, these patients frequently
present with additional gastrointestinal pathology that also influences their
quality of life and final prognosis. Congenital gastrointestinal anomalies are
often observed and the displacement of the liver, the stomach and/or the
intestines into the thorax may cause distortion of the vascular axis of these
organs, increasing the risk of congestion and/or ischemia. Some of these
gastrointestinal complications are already visible at imaging studies performed
in utero and/or in newborns.This pictorial essay describes the imaging findings
of the most frequently detected gastrointestinal complications in fetuses and
infants with congenital diaphragmatic hernia, focusing on prenatal exams.
PMID- 28695235
TI - Preoperative CT in patients with surgically resectable pancreatic adenocarcinoma:
does the time interval between CT and surgery affect survival?
AB - PURPOSE: The preoperative imaging-to-surgery time interval (ISI) influences the
risk of unexpected progression (UP) found at surgery for pancreatic
adenocarcinoma. We aimed to assess whether ISI influences disease recurrence
and/or survival. METHODS AND MATERIALS: A single-institution, ethics board
approved retrospective analysis of all patients who underwent attempted resection
of pancreatic (PDAC) or periampullary adenocarcinoma (AmpAC) between 1st January
2010 and 31st December 2015 was performed. All patients underwent preoperative
abdominal computed tomography (CT). Exclusion criteria were borderline resectable
disease and neoadjuvant chemo/radiotherapy. Patients were followed up until 30th
June 2016. The population was divided into ISI >=/<25 days. Kaplan-Meier and Cox
regression survival analyses were performed. RESULTS: 239 patients underwent
surgical exploration. UP was found in 29 (12.1%) and these patients had longer
ISI (median 46 vs. 29 days, p < 0.05). When intention-to-treat analysis was
performed, there was no difference in overall survival (OS) between patients with
ISI >=/<25. In those who underwent resection, ISI did not influence disease-free
survival (DFS) or OS for PDAC (n = 174). For AmpAC (n = 36), ISI >= 25 days was
associated with longer OS (p < 0.05) but did not influence DFS. Longer ISI was
independently associated with improved OS on regression analysis for AmpAC.
CONCLUSION: Performing surgery for resectable pancreatic adenocarcinoma within 25
days of abdominal CT reduces the chance of UP but does not confer a survival
benefit. For those who undergo resection of AmpAC, a longer ISI was associated
with longer OS. This probably represents a more biologically indolent disease in
this cohort.
PMID- 28695236
TI - Volumetric parameters on FDG PET can predict early intrahepatic recurrence-free
survival in patients with hepatocellular carcinoma after curative surgical
resection.
AB - PURPOSE: This study assessed the prognostic values of volumetric parameters on
18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in predicting
early intrahepatic recurrence-free survival (RFS) after curative resection in
patients with hepatocellular carcinoma (HCC). METHODS: A retrospective analysis
was performed on 242 patients with HCC who underwent staging FDG PET and
subsequent curative surgical resection. The tumor-to-non-tumorous liver uptake
ratio, metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of the HCC
lesions on PET were measured. The prognostic values of clinical factors and PET
parameters for predicting overall RFS, overall survival (OS), extrahepatic RFS,
and early and late intrahepatic RFS were assessed. RESULTS: The median follow-up
period was 54.7 months, during which 110 patients (45.5%) experienced HCC
recurrence and 62 (25.6%) died. Patients with extrahepatic and early intrahepatic
recurrence showed worse OS than did those with no recurrence or late intrahepatic
recurrence (p < 0.001). Serum bilirubin level, MTV, and TLG were independent
prognostic factors for overall RFS and OS (p < 0.05). Only MTV and TLG were
prognostic for extrahepatic RFS (p < 0.05). Serum alpha-fetoprotein and bilirubin
levels, MTV, and TLG were prognostic for early intrahepatic RFS (p < 0.05) and
hepatitis C virus (HCV) positivity and serum albumin level were independently
prognostic for late intrahepatic RFS (p < 0.05). CONCLUSION: Intrahepatic
recurrence showed different prognoses according to the time interval of
recurrence in which early recurrence had as poor survival as extrahepatic
recurrence. MTV and TLG on initial staging PET were significant independent
factors for predicting early intrahepatic and extrahepatic RFS in patients with
HCC after curative resection. Only HCV positivity and serum albumin level were
significant for late intrahepatic RFS, which is mainly attributable to the de
novo formation of new primary HCC.
PMID- 28695237
TI - Cytopathology of pericardial effusions : Experience from a tertiary center of
cardiology.
AB - BACKGROUND: Pericardial effusion (PE) is a common clinical condition that can
develop as a result of systemic or cardiac diseases. Here, we report the results
of cytology for patients who underwent pericardiocentesis for PE. METHODS: The
study comprised 283 patients who underwent primary percutaneous
pericardiocentesis between 2007 and 2016. The mean age of the patients was 60.0
+/- 16.6 years; 162 (57.2%) were male and 121 (42.8%) were female. The presence
of reactive mesothelial cells, acute and chronic inflammatory cells, and/or blood
without evidence of malignant cells was considered as benign. The presence of
malignant cells with/without reactive mesothelial cells, inflammatory cells,
and/or blood was considered as malignant. RESULTS: The vast majority of PE
specimens (219 cases; 77.4%) were classified as benign. Only 20 cases (7.1%) were
classified as atypical, and malignant cells were present in the PE specimens of
44 cases (15.5%). The most common diagnosis was benign PE. The most commonly
encountered malignancy was lung cancer. The rate of malignancy was 1.9% in the
serous group and 24% in the hemorrhagic group, which was statistically
significant. CONCLUSION: Benign PE was the most frequent cytological diagnosis in
our study. Chronic nonspecific pericarditis was the most frequent type of
pericarditis in the benign PE group, while lung adenocarcinoma was the most
frequent malignancy in the malignant PE group. The rate of malignancy was
significantly higher in the hemorrhagic group than in the serous group.
PMID- 28695238
TI - Predictive risk factors for systemic inflammatory response syndrome following
ureteroscopic laser lithotripsy.
AB - The objective of this study was to investigate risk factors for the development
of systemic inflammatory response syndrome following ureteroscopic laser
lithotripsy. We retrospectively collected data of 469 patients who underwent
ureteroscopic laser lithotripsy at our single institution from February 2008 to
June 2016. Details for the patient, the stone, and the surgical factors that
potentially contributed to postoperative infection were extracted. Using a
logistic regression model, we analyzed how the clinical factors affected the
incidence of systemic inflammatory response syndrome. Twenty-seven patients
(5.7%) were postoperatively diagnosed with systemic inflammatory response
syndrome; of these, 25 patients were diagnosed within 24 h after ureteroscopy.
One patient required intensive care unit admission, but no death was reported. A
preoperative stent was significantly associated with postoperative systemic
inflammatory response syndrome only on univariate analysis, and the reasons for
stenting were varied. Multivariate analysis revealed that obstructive
pyelonephritis, a positive preoperative bladder urine culture result, and female
gender were significantly associated with postoperative systemic inflammatory
response syndrome. Patients who experienced obstructive pyelonephritis preceding
ureteroscopic laser lithotripsy or had a positive preoperative bladder urine
culture result were at an increased risk of systemic inflammatory response
syndrome despite receiving appropriate preoperative antibiotic therapy. Regarding
the impact of a preoperative stent on postoperative infection, further
investigation focusing on reasons for stenting is needed.
PMID- 28695239
TI - Occurrence of Clinical Bone Fracture Following a Prolonged Stay in Intensive Care
Unit: A Retrospective Controlled Study.
AB - Clinical consequences of critical illness and critical care (CC) on bone health
remain largely unexplored. This retrospective study aimed to assess the number of
new bone fractures (BF) following a prolonged length of stay (LOS) in intensive
care unit (ICU). Adults admitted in our tertiary ICU during 2013 with a stay >7
days were included (CC group). Patients who died in ICU or lost to follow-up were
excluded. For each CC patient still alive after 2 years of follow-up, 2 control
patients, scheduled for surgery during 2013, were recruited and matched for
gender and age. Basal fracture risk before admission was calculated using FRAX
tool. General practitioners were phoned to check out new bone fracture (BF)
during 2 years after admission. Of the 457 enrolled CC patients, 207 did not meet
inclusion criteria and 72 died during FU (median age 72 [65-77] years). New BF
occurred in 9 of the 178 patients still alive at the end of FU (5%). Median age
of these patients was 64 [53-73] years. Fractured patients did not differ from
non-fractured ones based on demographic and clinical characteristics, excepting
for FRAX risks that were higher in fractured patients. In the control group, 327
patients were analyzed. Their rate of BF was 3.4% without statistical
significance compared to the CC group. FRAX risks were similar in both groups.
The risk of new BF in CC group, expressed as an odds ratio, was 50% higher than
in the control group without achieving statistical significance (odds ratio 1.53;
95% confidence interval 0.62-3.77; p = 0.35). When comparing ICU survivors to
patients who underwent uncomplicated surgery in the present preliminary study
included limited cohorts, the fracture risk in the 2 years following prolonged
ICU stay was not statistically higher. However, CC fractured patients had higher
FRAX risks than non-fractured patients. Such screening could help to target
prevention and appropriate treatment strategies.
PMID- 28695240
TI - [Vocational policy - bridge between science and daily medical practice].
PMID- 28695241
TI - [Metastatic prostate cancer : Update: position paper for the use of
chemotherapy].
AB - BACKGROUND: Taxen-based chemotherapy has been established as an effective
treatment option in castration-resistant metastatic prostate cancer (mCRPC).
Randomized phase III studies, however, have shown that even in the hormone-naive
metastatic state, the early use of chemotherapy in addition to the classical
androgen deprivation therapy (ADT) approach leads to a significant increase in
median overall survival. OBJECTIVE: This position paper aims to provide current
data and orientation in the evidence-based treatment of mPC patients in daily
clinical practice. MATERIALS AND METHODS: A German group of clinical experts
analyzed the current data and developed criteria for the treatment of mPC
patients in daily clinical practice. RESULTS: In the current treatment of hormone
naive mPC, a beneficial effect of chemotherapy in addition to ADT has become
evident. Provided patients are in an appropriate condition, those with a high
metastatic load should receive chemotherapy in addition to ADT. Especially in
high-risk mCRPC patients (PSA >114 ng/ml, visceral metastasis, ADT response <12
months, tumor-associated complaints), first-line chemotherapy is indicated. After
docetaxel failure, continuous treatment with cabazitaxel shows superior overall
survival compared to sustained antihormonal therapy. CONCLUSION: Chemotherapy is
firmly established in treating patients with mCRPC. Long-term, it will be
important to identify molecular predictors. The authors suggest the early use of
chemotherapy in hormone-naive mPC, but note that the approval in this indication
is currently nonexistent. After disease progression, patients should be treated
analogous to mCRPC.
PMID- 28695242
TI - Spine fracture prevalence in a nationally representative sample of US women and
men aged >=40 years: results from the National Health and Nutrition Examination
Survey (NHANES) 2013-2014---supplementary presentation.
AB - Spine fracture prevalence is similar in men and women, increasing from <5% in
those <60 to 11% in those 70-79 and 18% in those >=80 years. Prevalence was
higher with age, lower bone mineral density (BMD), and in those meeting criteria
for spine imaging. Most subjects with spine fractures were unaware of them.
PMID- 28695243
TI - CNS metabolism in high-risk drug abuse : Insights gained from 1H-, 31P-MRS and
PET.
AB - BACKGROUND: High-risk drug consumption is a matter of great concern for public
health actors in industrialised countries. The latest trends show a market
tendency towards diversification and increasing demand for high-purity synthetic
drugs. While most consumers seek medical help after cannabis use, it is high-risk
drugs like cocaine, heroin and amphetamines that account for most of the 1000
drug-related deaths that occur in Germany every year. PURPOSE: This article
presents the most prominent in vivo cerebral metabolic information in cocaine,
heroin and methamphetamine users provided by MRI spectroscopy and PET imaging.
MATERIALS AND METHODS: We reviewed the literature reporting neuroimaging studies
of in vivo metabolic data for methamphetamine, cocaine and heroin consumption
published up to March 2017. The search was conducted using PubMed and a
combination of the following key words: methamphetamine, cocaine, heroin, MR
spectroscopy, PET. CONCLUSION: MRI and PET are indispensable tools in gauging
brain metabolic response to illegal drug abuse. Future breakthroughs in this
field will most likely come from the investigation of novel neurotransmitter
systems in PET and imaging phosphorus and carbon metabolites in MRI.
PMID- 28695244
TI - [Diagnostic and treatment standards for cerebral sinus venous thrombosis :
Results of an online survey of German stroke units].
AB - BACKGROUND AND PURPOSE: The aim of this survey was to characterize the current
diagnostic and therapeutic strategies for thrombosis of the cerebral sinus and
veins (CVT) performed in German stroke units (SU). METHODS: Between September
2015 and January 2016 all clinical heads of certified SUs in Germany were invited
to participate in a standardized online survey. The survey concentrated on the
basic characteristics of SUs, diagnostic and therapeutic procedures and was made
anonymous if so desired. Frequencies were expressed as percentages and
differences between regional stroke units (RSU) and supraregional (i. e.
comprehensive) SUs (SRSU) were compared with the chi2-test or Fisher's test
RESULTS: A total of 107 SU heads participated (response rate 42.8%) and 55.1% of
these were RSUs. In 77.2% the diagnosis is made by magnetic resonance imaging
angiography (MR-A, RSU 81.1% vs. SRSU 72.3%; p = 0.29). Of the SUs 79.1%
determined d-dimer if CVT is suspected (79.3% vs. 78.7%; p = 0.94) and 88.5%
carried out screening for thrombophilia (89.5% vs. 87.2%; p = 0.72). Intravenous
unfractionated heparin (67.2% vs. 70.2%; p = 0.74) or subcutaneous low molecular
weight heparin (32.8% vs. 29.8%; p = 0.74) are first line therapy in all SUs.
Invasive procedures, such as hypothermia (3.7% vs. 10.6%; p = 0.25),
hemicraniectomy (26% vs. 63.9%; p = 0.0001), endovascular techniques (11.1% vs.
40.4%; p = 0.0007) and systemic thrombolysis (5.5% vs. 10.6%; p = 0.47) are
performed more frequently in SRSUs. Of the SUs 18.5% already use new oral
anticoagulants (10.7% vs. 27.7%; p = 0.027). Most of the SUs organize a follow-up
visit (70.9% vs. 76.6%; p = 0.52) with a MRI (94.2% vs. 91.1%; p = 0.7) within
the first 6 months. CONCLUSION: The survey revealed substantial homogeneity
between RSUs and SRSUs and standards are mostly in line with the guidelines. Non
established procedures, such as invasive therapeutic procedures and the
administration of new oral anticoagulants were used significantly more often in
SRSUs.
PMID- 28695245
TI - Risk Factors for Peri-Procedural Arterial Ischaemic Stroke in Children with
Cardiac Disease.
AB - Improved survival of children with congenital heart disease has led to increasing
focus on neurodevelopmental outcome, as close to half of the infants undergoing
cardiac surgery are affected by neurodevelopmental disability. Stroke is
particularly important as it frequently results in permanent neurologic sequelae.
The aim of this study was to investigate risk factors for peri-procedural
arterial ischaemic stroke (AIS) in children with cardiac disease. A retrospective
case-control analysis of children aged <18 years with radiologically confirmed
AIS following a cardiac procedure admitted to the Royal Children's Hospital
Melbourne between 1993 and 2010. Each case was matched with two controls with
similar cardiac diagnosis, procedure type, age and date of procedure.
Demographics and peri-procedural data were collected from medical records and
departmental database. Fifty-two cases were identified. Multivariable analysis
identified post-procedural infection (OR 6.1, CI 1.3-27, p = 0.017) and length of
ICU stay (OR 4.0, CI 1.4-11, p = 0.009) as risk factors for AIS. Although the
study is limited to a single-centre cohort, length of ICU stay and post
procedural infection were identified as risk factors for AIS. These findings
demonstrate these factors to be important areas to focus attention for stroke
prevention in children with cardiac disease.
PMID- 28695246
TI - Intensity-modulated radiation therapy followed by GDP chemotherapy for newly
diagnosed stage I/II extranodal natural killer/T cell lymphoma, nasal type.
AB - Extranodal natural killer (NK)/T cell lymphoma, nasal type (ENKTL) is an
aggressive non-Hodgkin lymphoma and the majority of ENKTL cases are diagnosed at
the localized stage. Radiotherapy in combination with chemotherapy has been used
for localized ENKTL, but the optimal combination treatment modality and the best
first-line chemotherapy regimen have not been defined. In this retrospective
study, 44 patients with newly diagnosed, stages I/II ENKTL were enrolled and
received intensity-modulated radiation therapy (IMRT, 50-56 Gy) followed by GDP
(gemcitabine, dexamethasone, and cisplatin) chemotherapy. The median number of
chemotherapy cycles per patient was 4 (range, 2-6 cycles). At the end of
treatment, the overall response rate was 95% (42/44), including 39 patients (89%)
who attained complete response. Two patients developed systemic progression after
IMRT. With a median follow-up of 37.5 months, the 3-year overall survival (OS)
rate and progression-free survival (PFS) rate were 85% (95% CI, 74 to 96%) and
77% (95% CI, 64 to 91%), respectively. Locoregional and systemic failure rates
for this treatment were 9% (4/44) and 14% (6/44), respectively. The most common
grades 3 to 4 adverse events included leukopenia (37%), neutropenia (34%), and
mucositis (25%). No treatment-related deaths were observed. This study suggested
high efficacy and low toxicity of IMRT followed by GDP regimen chemotherapy for
newly diagnosed stage I/II ENKTL patients. These results require further
investigation in prospective trials.
PMID- 28695247
TI - [Ileoanal pouch].
PMID- 28695249
TI - First study on iron complexes in blood and organ samples from thalassaemic and
normal laboratory mice using Mossbauer spectroscopy.
AB - Measurements of iron complexes and iron stores in the body are crucial for
evaluation and management of chelation therapy targeted against iron accumulation
or overload in blood and organs. In this work, blood and tissue samples from one
normal and one thalassaemic laboratory mouse were studied using 57Fe Mossbauer
spectroscopy at 78 K for the first time. In contrast to human patients, these
laboratory mice did not receive any medical treatment, thus the iron components
present in the samples are not altered from their natural state. The Mossbauer
spectra of blood, liver and spleen samples of the thalassaemic mouse were found
to differ in shape and iron content compared with corresponding spectra of the
normal mouse. These results demonstrate a basis for further exploitation of the
thalassaemic mouse model to study thalassaemia and its treatment in more detail
using Mossbauer spectroscopy.
PMID- 28695248
TI - Divergent effects of anesthetics on lipid bilayer properties and sodium channel
function.
AB - General anesthetics revolutionized medicine by allowing surgeons to perform more
complex and much longer procedures. This widely used class of drugs is essential
to patient care, yet their exact molecular mechanism(s) are incompletely
understood. One early hypothesis over a century ago proposed that nonspecific
interactions of anesthetics with the lipid bilayer lead to changes in neuronal
function via effects on membrane properties. This model was supported by the
Meyer-Overton correlation between anesthetic potency and lipid solubility and
despite more recent evidence for specific protein targets, in particular ion
channels, lipid bilayer-mediated effects of anesthetics is still under debate. We
therefore tested a wide range of chemically diverse general anesthetics on lipid
bilayer properties using a sensitive and functional gramicidin-based assay. None
of the tested anesthetics altered lipid bilayer properties at clinically relevant
concentrations. Some anesthetics did affect the bilayer, though only at high
supratherapeutic concentrations, which are unlikely relevant for clinical
anesthesia. These results suggest that anesthetics directly interact with
membrane proteins without altering lipid bilayer properties at clinically
relevant concentrations. Voltage-gated Na+ channels are potential anesthetic
targets and various isoforms are inhibited by a wide range of volatile
anesthetics. They inhibit channel function by reducing peak Na+ current and
shifting steady-state inactivation toward more hyperpolarized potentials. Recent
advances in crystallography of prokaryotic Na+ channels, which are sensitive to
volatile anesthetics, together with molecular dynamics simulations and
electrophysiological studies will help identify potential anesthetic interaction
sites within the channel protein itself.
PMID- 28695250
TI - Detection and Monitoring of Oil Spills Using Moderate/High-Resolution Remote
Sensing Images.
AB - Current marine oil spill detection and monitoring methods using high-resolution
remote sensing imagery are quite limited. This study presented a new bottom-up
and top-down visual saliency model. We used Landsat 8, GF-1, MAMS, HJ-1 oil spill
imagery as dataset. A simplified, graph-based visual saliency model was used to
extract bottom-up saliency. It could identify the regions with high visual
saliency object in the ocean. A spectral similarity match model was used to
obtain top-down saliency. It could distinguish oil regions and exclude the other
salient interference by spectrums. The regions of interest containing oil spills
were integrated using these complementary saliency detection steps. Then, the
genetic neural network was used to complete the image classification. These steps
increased the speed of analysis. For the test dataset, the average running time
of the entire process to detect regions of interest was 204.56 s. During image
segmentation, the oil spill was extracted using a genetic neural network. The
classification results showed that the method had a low false-alarm rate (high
accuracy of 91.42%) and was able to increase the speed of the detection process
(fast runtime of 19.88 s). The test image dataset was composed of different types
of features over large areas in complicated imaging conditions. The proposed
model was proved to be robust in complex sea conditions.
PMID- 28695251
TI - Identification of Spilled Oil from the MV Marathassa (Vancouver, Canada 2015)
Using Alkyl PAH Isomer Ratios.
AB - On the morning of April 9, 2015, citizens in Vancouver (British Columbia, Canada)
awoke to the sight and smell of oil on the shores of popular downtown beaches.
Because the oil also had spread over the shallow seawater intakes for the
Vancouver Aquarium, a preliminary screening of samples was performed as a prompt,
first response to assess the risks to the Aquarium collection and guide the
emergency operational response. A subsequent, more detailed examination for the
presence of spilled oil in sediment, biota and water samples from the Vancouver
Harbour region was then conducted based on the analysis of a large suite of
alkanes, petroleum biomarkers, parent polycyclic aromatic hydrocarbons (PAHs) and
alkyl PAH isomers. Most of the commonly applied biomarker ratios exhibit similar
values for the spilled oil, Alberta oil (the main petroleum source for British
Columbia), and pre-spill and un-oiled sediment samples. In contrast, alkyl PAH
isomer ratios showed a clear distinction between the spilled oil and pre-spill
samples, with the largest differences shown by isomers of the methyl
fluoranthene/pyrene alkyl PAH series. This novel use of alkyl PAH isomers for
fingerprinting petroleum helped to confirm the grain carrier MV Marathassa as the
source of the oil that affected beach and mussel samples to document definitively
the spread of the oil and to establish which samples contained a mix of the oil
and hydrocarbons linked to historical activities. Finally, an initial evaluation
of the biological risks of the MV Marathassa oil spill in Vancouver Harbour
showed that oiled beach sediments had priority parent PAH concentrations that are
likely to harm marine life.
PMID- 28695252
TI - Oil Spills and Marine Mammals in British Columbia, Canada: Development and
Application of a Risk-Based Conceptual Framework.
AB - Marine mammals are inherently vulnerable to oil spills. We developed a conceptual
framework to evaluate the impacts of potential oil exposure on marine mammals and
applied it to 21 species inhabiting coastal British Columbia (BC), Canada. Oil
spill vulnerability was determined by examining both the likelihood of species
specific (individual) oil exposure and the consequent likelihood of population
level effects. Oil exposure pathways, ecology, and physiological characteristics
were first used to assign species-specific vulnerability rankings. Baleen whales
were found to be highly vulnerable due to blowhole breathing, surface filter
feeding, and invertebrate prey. Sea otters (Enhydra lutris) were ranked as highly
vulnerable due to their time spent at the ocean surface, dense pelage, and
benthic feeding techniques. Species-specific vulnerabilities were considered to
estimate the likelihood of population-level effects occurring after oil exposure.
Killer whale (Orcinus orca) populations were deemed at highest risk due to small
population sizes, complex social structure, long lives, slow reproductive
turnover, and dietary specialization. Finally, we related the species-specific
and population-level vulnerabilities. In BC, vulnerability was deemed highest for
Northern and Southern Resident killer whales and sea otters, followed by Bigg's
killer whales and Steller sea lions (Eumetopias jubatus). Our findings challenge
the typical "indicator species" approach routinely used and underscore the need
to examine marine mammals at a species and population level for risk-based oil
spill predictions. This conceptual framework can be combined with spill
probabilities and volumes to develop more robust risk assessments and may be
applied elsewhere to identify vulnerability themes for marine mammals.
PMID- 28695253
TI - Long-Term Monitoring of PAH Contamination in Sediment and Recovery After the
Hebei Spirit Oil Spill.
AB - Approximately 10,900 t of crude oil was released 10 km off the west coast of
Korea after the collision between the oil tanker Hebei Spirit and a barge
carrying a crane in December 2007. To assess the areal extent and temporal trends
of PAH contamination, 428 sediment samples were collected from December 2007
through May 2015 for PAH analysis. Sedimentary PAH concentrations measured
immediately after the spill ranged from 3.2 to 71,200 ng g-1, with a mean of 3800
ng g-1. Increases in PAH concentrations were observed at stations 7-23, which
were heavily oiled due to tidal currents and northwesterly wind that transported
the spilled oil to these locations. Mean and maximum PAH concentrations decreased
drastically from 3800 to 88.5 and 71,200 to 1700 ng g-1, respectively, 4 months
after the spill. PAH concentrations highly fluctuated until September 2008 and
then decreased slowly to background levels. Reduction rate was much faster at the
sandy beaches (k = 0.016) than in the muddy sites (k = 0.001). In muddy
sediments, low attenuation due to low flushing rate in the mostly anaerobic
sediment possibly contributed the persistence of PAHs. By May 2015 (~7.5 years
after the spill), mean and maximum PAH concentrations decreased by 54 and 481
times, respectively, compared with the peak concentrations. The sedimentary PAH
concentrations in the monitoring area have returned to regional background
levels.
PMID- 28695254
TI - Contamination and Human Health Risk Assessment of Polycyclic Aromatic
Hydrocarbons (PAHs) in Oysters After the Wu Yi San Oil Spill in Korea.
AB - After the collision of the Singapore-registered oil tanker M/V Wu Yi San into the
oil terminal of Yeosu, Korea on January 31, 2014, approximately 900 m3 of oil and
oil mixture were released from the ruptured pipelines. The oil affected more than
10 km of coastline along Gwangyang Bay. Emergency oil spill responses recovered
bulk oil at sea and cleaned up the stranded oil on shore. As part of an emergency
environmental impact assessment, region-wide monitoring of oil contamination in
oyster had been conducted for 2 months. Highly elevated concentrations of
polycyclic aromatic hydrocarbons (PAHs) were detected at most of the spill
affected sites. Four days after the spill, the levels of PAHs in oysters
increased dramatically to 627-81,000 ng/g, the average of which was 20 times
higher than those found before the spill (321-4040 ng/g). The level of PAHs in
these oysters increased until 10 days after the spill and then decreased. Due to
the strong tidal current and easterly winter winds, the eastern part of the Bay
the Namhae region-was heavily contaminated compared with other regions. The
accumulation and depuration of spilled oil in oyster corresponded with the
duration and intensity of the cleanup activities, which is the first field
observation in oil spill cases. Human health risk assessments showed that
benzo[a]pyrene equivalent concentrations exceeded levels of concern in the highly
contaminated sites, even 60 days after the spill.
PMID- 28695255
TI - Biomarkers of Aryl-hydrocarbon Receptor Activity in Gulf Killifish (Fundulus
grandis) From Northern Gulf of Mexico Marshes Following the Deepwater Horizon Oil
Spill.
AB - Following the Deepwater Horizon oil spill, shorelines throughout the Barataria
Basin of the northern Gulf of Mexico in Louisiana were heavily oiled for months
with Macondo-252 oil, potentially impacting estuarine species. The Gulf killifish
(Fundulus grandis) has been identified as a sentinel species for the study of
site-specific effects of crude oil contamination on biological function. In
November and December 2010, 4-5 months after the Macondo well was plugged and new
oil was no longer spilling into the Gulf waters, Gulf killifish were collected
across the Barataria Basin from 14 sites with varying degrees of oiling. Fish
collected from oiled sites exhibited biological indications of exposure to oil,
including increase in cytochrome P4501A (CYP1A) mRNA transcript and protein
abundances in liver tissues. Immunohistochemistry revealed increases in gill,
head kidney, and intestinal CYP1A protein at heavily oiled sites. Intestinal
CYP1A protein was a sensitive indicator of exposure, indicating that intestinal
tissue plays a key role in biotransformation of AHR ligands and that ingestion is
a probable route of exposure, warranting additional consideration in future
studies.
PMID- 28695256
TI - Anomalously High Recruitment of the 2010 Gulf Menhaden (Brevoortia patronus) Year
Class: Evidence of Indirect Effects from the Deepwater Horizon Blowout in the
Gulf of Mexico.
AB - Gulf menhaden (Brevoortia patronus) exhibited unprecedented juvenile recruitment
in 2010 during the year of the Deepwater Horizon well blowout, exceeding the
prior 39-year mean by more than four standard deviations near the Mississippi
River. Abundance of that cohort remained exceptionally high for two subsequent
years as recruits moved into older age classes. Such changes in this dominant
forage fish population can be most parsimoniously explained as consequences of
release from predation. Contact with crude oil induced high mortality of
piscivorous seabirds, bottlenose dolphin (Tursiops truncatus), waders, and other
fish-eating marsh birds, all of which are substantial consumers of Gulf menhaden.
Diversions of fresh water from the Mississippi River to protect coastal marshes
from oiling depressed salinities, impairing access to juvenile Gulf menhaden by
aquatic predators that avoid low-salinity estuarine waters. These releases from
predation led to an increase of Gulf menhaden biomass in 2011 to 2.4 million t,
or more than twice the average biomass of 1.1 million t for the decade prior to
2010. Biomass increases of this magnitude in a major forage fish species suggest
additional trophically linked effects at the population-, trophic-level and
ecosystem scales, reflecting an heretofore little appreciated indirect effect
that may be associated with major oil spills in highly productive marine waters.
PMID- 28695257
TI - The Montara Oil Spill: A 2009 Well Blowout in the Timor Sea.
AB - A well on the Montara platform on the Australian continental shelf blew out in
August 2009 and spilled oil into the Timor Sea for 74 days. The oil, estimated at
as much as 23.5 million L in total volume, spread over a large area of the shelf
and eventually into Indonesian waters. This paper documents, through published
literature, reports of both Australian and Indonesian governments and
observations of coastal residents and fishermen the spread of the oil and
attempts to estimate its impact. The lack of observers on the ocean and baseline,
pre-spill data on populations of marine organisms, and delays in deploying
scientific surveys after the spill severely limited efforts by the Australian
government to determine damage in its territorial waters. Biological survey work
was not done in Indonesian waters, but coastal residents attested to relatively
severe impacts to algal farms. In addition fish landings declined in one port in
southwest Timor Island.
PMID- 28695258
TI - Environmental Impacts and Recovery After the Hebei Spirit Oil Spill in Korea.
AB - The Hebei Spirit oil spill (HSOS) on December 7, 2007 was the worst oil spill
recorded in Korea, with the release of approximately 10,900 tons of crude oil and
375 km of coastline polluted along the west coast of Korea. Cleanup operation was
conducted by official and contract responders as well as volunteers for massive
oil containment and removal of heavy accumulations of stranded oil. Together with
the oil cleanup, a long-term environmental impact assessment (EIA) of the HSOS
was initiated based on the Marine Environmental Management Act, which covers oil
contamination in a multimedia environment, toxic effects on organisms, and
ecosystem injury. This review summarizes the long-term monitoring results of HSOS
EIA focused on (1) pollution status of seawater, sediment, and bivalves, (2)
ecotoxicological effects, and (3) ecosystem recovery. Overall, concentrations of
petroleum hydrocarbons in the environment indicated that their concentrations
were well down to at or near background or pre-spill contamination levels at most
sites after 1 year. The potential toxic effects of residual oils in sediments
have decreased to background levels in most coastal areas of Taean. The entire
ecosystem in the most affected area of the Taean coasts appear to be
considerably, but not fully, recovered at present, namely after 8 years of the
HSOS. The presence of lingering oil and elevated contamination levels at several
sites still require continuous long-term monitoring.
PMID- 28695259
TI - Photoenhanced Toxicity of Petroleum to Aquatic Invertebrates and Fish.
AB - Photoenhanced toxicity is a distinct mechanism of petroleum toxicity that is
mediated by the interaction of solar radiation with specific polycyclic aromatic
compounds in oil. Phototoxicity is observed as a twofold to greater than 1000
fold increase in chemical toxicity to aquatic organisms that also have been
exposed to light sources containing sufficient quantity and quality of
ultraviolet radiation (UV). When tested under natural sunlight or laboratory
sources of UV, fresh, and weathered middle distillates, crudes and heavy oils can
exhibit photoenhanced toxicity. These same products do not exhibit phototoxicity
in standard test protocols because of low UV irradiance in laboratory lighting.
Fresh, estuarine, and marine waters have been shown to have sufficient solar
radiation exposure to elicit photoenhanced toxicity, and a diversity of aquatic
invertebrate and fish species can exhibit photoenhanced toxicity when exposed to
combinations of oil and UV. Risks of photoenhanced toxicity will be greatest to
early life stages of aquatic organisms that are translucent to UV and that
inhabit the photic zone of the water column and intertidal areas exposed to oil.
PMID- 28695260
TI - Challenges to Oil Spill Assessment for Seabirds in the Deep Ocean.
AB - We synthesize impediments for evaluating effects to seabirds from open ocean
hydrocarbon releases. Effects on seabirds from ship discharges, spills, and well
blowouts often are poorly detected and monitored far from land. Regulatory
regimes for ocean spills can result in monitoring efforts that are not entirely
transparent. We illustrate how interdisciplinary technologies address deficits
that hamper individual or population level assessments for seabirds, and we
demonstrate where emerging technologies might be engaged to bridge gaps in oil
spill monitoring. Although acute mortality from direct oil exposure poses the
greatest risk to seabirds, other hazards from light-attraction, flaring,
collisions, chronic pollution, and hydrocarbon inhalation around oil
infrastructure also may induce bird mortality in the deep ocean.
PMID- 28695261
TI - Molecular Mechanisms of Crude Oil Developmental Toxicity in Fish.
AB - With major oil spills in Korea, the United States, and China in the past decade,
there has been a dramatic increase in the number of studies characterizing the
developmental toxicity of crude oil and its associated polycyclic aromatic
compounds (PACs). The use of model fish species with associated tools for genetic
manipulation, combined with high throughput genomics techniques in nonmodel fish
species, has led to significant advances in understanding the cellular and
molecular bases of functional and morphological defects arising from embryonic
exposure to crude oil. Following from the identification of the developing heart
as the primary target of crude oil developmental toxicity, studies on individual
PACs have revealed a diversity of cardiotoxic mechanisms. For some PACs that are
strong agonists of the aryl hydrocarbon receptor (AHR), defects in heart
development arise in an AHR-dependent manner, which has been shown for potent
organochlorine agonists, such as dioxins. However, crude oil contains a much
larger fraction of compounds that have been found to interfere directly with
cardiomyocyte physiology in an AHR-independent manner. By comparing the cellular
and molecular responses to AHR-independent and AHR-dependent toxicity, this
review focuses on new insights into heart-specific pathways underlying both acute
and secondary adverse outcomes to crude oil exposure during fish development.
PMID- 28695262
TI - The Toxicity to Fish Embryos of PAH in Crude and Refined Oils.
AB - Oil spills are a potential threat to the recruitment and production of fish.
Polycyclic aromatic hydrocarbons (PAH), particularly 3-5-ringed alkyl PAH, are
components of oil that cause chronic embryotoxicity. Toxicity is related to
molecular size and octanol-water partition coefficients (Kow), indicating that
water-lipid partitioning controls exposure and tissue dose. Nevertheless, more
than 25% of the variation in toxicity among congeners is unexplained. Congeners
with the same number of rings, alkyl carbon atoms, and Kow, but different
molecular shapes, have markedly different toxicities, likely due to differences
in interactions with cellular receptors. The potentiation and antagonism of
metabolism and toxicity in PAH mixtures suggest that measured effect
concentrations for individual PAH are conservative. Because mixture interactions
are not well understood, total PAH concentrations >0.1 ug/L following oil spills
should be considered hazardous.
PMID- 28695263
TI - Advances in Understanding the Fate and Effects of Oil from Accidental Spills in
the United States Beginning with the Exxon Valdez.
AB - Scientific studies of the environmental effects of oil spills in the United
States have produced a steady stream of unexpected discoveries countering prior
and often simplistic assumptions. In this brief review, I present how major
discoveries from scientific studies of oil spill effects on marine ecosystems and
environments, beginning with the 1989 Exxon Valdez, have led to a more informed
appreciation for the complexity and the severity of the damage that major spills
can do to marine ecosystems and to an increasing recognition that our ability to
evaluate those damages is very limited, resulting in a structural bias toward
underestimation of adverse environmental effects.
PMID- 28695264
TI - Marine Environmental Emergencies in the North Pacific Ocean: Lessons Learned from
Recent Oil Spills.
AB - Increasing marine vessel traffic, and oil and gas exploration and development
throughout the North Pacific basin brings increasing risks of oil spills.
Recognizing the serious challenges presented to response authorities, this
Special Issue was organized by the North Pacific Marine Science Organization to
provide an introduction to the current state of scientific understanding
regarding the environmental effects of oil spills. Because interactions of
spilled oils with biota and their habitats are complex, the most serious
environmental damages from these spills are not necessarily those of greatest
immediate concern by the public. Our overarching goal for this Special Issue is
to provide an efficient introduction to the most important ways that oil spills
can harm biota, habitats, and ecosystems through invited, targeted mini-reviews
augmented by original research articles. We provide a brief background on the
challenges posed by large oil spills to response authorities, summarize findings
from the articles published in this Special Issue, and highlight some key
research needs.
PMID- 28695265
TI - Conservation of Erwinia amylovora pathogenicity-relevant genes among Erwinia
genomes.
AB - The Erwinia genus comprises species that are plant pathogens, non-pathogen,
epiphytes, and opportunistic human pathogens. Within the genus, Erwinia amylovora
ranks among the top 10 plant pathogenic bacteria. It causes the fire blight
disease and is a global threat to commercial apple and pear production. We
analyzed the presence/absence of the E. amylovora genes reported to be important
for pathogenicity towards Rosaceae within various Erwinia strains genomes. This
simple bottom-up approach, allowed us to correlate the analyzed genes to
pathogenicity, host specificity, and make useful considerations to drive targeted
studies.
PMID- 28695266
TI - Erratum to: Is there any benefit using low-intensity inspiratory and peripheral
muscle training in heart failure? A randomized clinical trial.
PMID- 28695267
TI - Impact of an alternative steroid on the relative bioavailability and
bioequivalence of a novel versus the originator formulation of abiraterone
acetate.
AB - PURPOSE: The originator abiraterone acetate (OAA) formulation is used for the
treatment of metastatic castration-resistant prostate cancer (mCRPC). This study
evaluated the bioavailability and bioequivalence of a novel formulation,
abiraterone acetate fine particle (AAFP), versus OAA on a steady-state background
of steroids. METHODS: Thirty-seven healthy male subjects were randomized in a
crossover design to receive methylprednisolone (4 mg twice daily) or prednisone
(5 mg twice daily) for 12 days in Period 1. On Day 11 of Period 1, subjects given
methylprednisolone received a single dose of AAFP 500 mg, and subjects given
prednisone received a single dose of OAA 1000 mg under fasted conditions. After a
2-week steroid washout period, subjects received the alternate treatments in
Period 2. RESULTS: There were no statistical differences regarding area under the
curve (AUC) and maximum concentration (C max) between AAFP and OAA. The
bioavailability of abiraterone from AAFP versus OAA by geometric mean ratio was
AUC0-infinity, 95.9% (90% confidence interval [CI] 86.0-106.9); AUC0-t , 99.2%
(88.7-110.9); and C max, 116.8% (102.2-133.4). The coefficient of variation (CV)
was smaller for AAFP versus OAA (AUC0-infinity, CV 44.23 vs. 55.61%; AUC0-t ,
45.17 vs. 58.16%; C max, 54.55 vs. 65.65%, respectively). Both treatments were
safe and well tolerated. CONCLUSIONS: AAFP plus methylprednisolone provided
abiraterone exposure that was comparable to OAA plus prednisone with respect to C
max and AUC. Less drug exposure variability was observed with AAFP compared with
OAA. Reduced pharmacokinetic variability may positively influence clinical
outcomes and warrants further study in mCRPC patients.
PMID- 28695268
TI - Risk of venous and arterial thromboembolic events associated with VEGFR-TKIs: a
meta-analysis.
AB - The reported incidence of arterial and venous thromboembolic events varies
markedly between VEGFR-TKI-related clinical trials. Here, we performed a meta
analysis to determine the incidence and the relative risk (RR) of venous
thromboembolism events (VTEs) and arterial thromboembolic events (ATEs)
associated with these agents. Databases (PubMed, Web of Science) were searched
for relevant studies. Statistical analyses were conducted to calculate the
summary incidences, RRs and 95% confidence intervals (CIs) using either random
effects or fixed-effects models according to the heterogeneity of the included
studies. A total of 24,855 patients from 48 studies were included. The overall
incidence of all-grade and high-grade VTEs associated with VEGFR-TKIs was 3.6%
(95% CI 2.3-5.2%) and 1.6% (95% CI 1.0-2.4%), respectively. The use of VEGFR-TKIs
did not significantly increase the risk of developing all-grade (RR 0.91; 95% CI
0.68-1.22; P = 0.558) and high-grade (RR 1.05; 95% CI 0.84-1.31; P = 0.769) VTEs.
The overall incidence of all-grade and high-grade ATEs associated with VEGFR-TKIs
was 2.7% (95% CI 1.7-3.6%) and 0.6% (95% CI 0.2-1.2%), respectively. The use of
VEGFR-TKIs significantly increase the risk of developing all-grade (RR 3.09; 95%
CI 1.41-6.76; P = 0.033) ATEs, and a tendency to increase the risk of high-grade
(RR 1.49; 95% CI 0.99-2.24; P = 0.101) ATEs was also detected. Patients with
cancer that receive VEGFR-TKIs are at high risk of developing ATEs. Physicians
should be aware of these adverse effects and should monitor cancer patients
receiving VEGFR-TKIs.
PMID- 28695269
TI - Erratum to: Underreporting of congenital rubella in Italy, 2010-2014.
PMID- 28695270
TI - Maternal use of prednisolone is unlikely to be associated with neonatal adrenal
suppression-a single-center study of 16 cases.
AB - : The use of supra-physiological, exogenous corticosteroids in pregnancy may lead
to neonatal adrenal suppression. We report on a single-center, case series study
carried out between 2006 and 2014, which included all newborns (n = 16) of
mothers using prednisolone >=10 mg/day during pregnancy. Newborns were routinely
assessed according to hospital protocol, with follow-up until 6 weeks after
birth. We investigated the clinical symptoms and biochemical findings of adrenal
suppression occurring in the newborns. Mean dose of maternal prednisolone was
29.7 +/- 16.1 mg/day with a mean duration of 18.4 +/- 15.4 weeks. Five newborns
showed hypoglycemia with normal serum cortisol concentrations and urinary steroid
profiles. Two newborns had abnormal urinary steroid profiles, probably the result
of prematurity, but with adequate adrenal stress response during clinical sepsis.
CONCLUSION: In this retrospective case series, we found no evidence of prolonged
effects of maternal prednisolone use during pregnancy on the neonatal
hypothalamic-pituitary-adrenal axis. What is known: * The use of prednisolone
during pregnancy may cause increased steroid levels in the fetus by partially
passing through the placenta. * So far, there was very limited data available on
the occurrence of adrenal suppression in the newborn of mothers using
prednisolone during pregnancy. What is new: * The use of high-dosage prednisolone
during pregnancy for >=1 week (mean duration of 18.4 +/- 15.4 weeks), prior to
delivery, appears to have little influence on the neonatal hypothalamic-pituitary
adrenal axis.
PMID- 28695271
TI - The metabolic costs of walking and running up a 30-degree incline: implications
for vertical kilometer foot races.
AB - PURPOSE: Vertical kilometer (VK) races, in which runners gain 1000 m of elevation
in <5000 m of distance, are becoming popular. However, few studies on steep
uphill running (>25 degrees ) exist. Previously, we determined that ~30 degrees
is the optimal angle for uphill running, costing the least amount of metabolic
energy for a specific vertical velocity. To inform the training and strategy of
VK racers, we quantified the metabolic cost of walking and running at various
velocities up a 30 degrees incline. METHODS: At 30 degrees , 11 experienced
runners (7 M, 4 F, 30.8 +/- 7.9 years, 1.71 +/- 0.08 m, 66.7 +/- 9.4 kg) walked
and ran for 5-min trials with 5-min rest between. Starting at 0.3 ms-1, we
increased treadmill velocity by 0.1 ms-1 for each trial until subjects could not
maintain the set velocity. We measured oxygen uptake (ml O2 kg-1 min-1) and
metabolic power (W kg-1 = metabolic energy per unit time per unit body mass) and
calculated metabolic costs of walking (C w) and running (C r) per unit distance
(J kg-1 m-1). RESULTS: Oxygen uptake and metabolic power increased linearly with
velocity. Between 0.3 and 0.7 ms-1, C w < C r. At 0.8 ms-1 there was no
difference and extrapolation suggests that at faster velocities, running likely
costs less than walking. CONCLUSION: On a 30 degrees incline, metabolic power
increases linearly with velocity. At speeds slower than 0.7 ms-1, walking
requires less metabolic power than running (W kg-1) suggesting most VK racers
should walk rather than run.
PMID- 28695272
TI - Cardiovascular effects of histamine in three widely diverse species of reptiles.
AB - The cardiovascular system of vertebrates is regulated by a vast number of
regulatory factors, including histamine. In pythons, histamine induces a strong
tachycardia and dilates the systemic vasculature, which resembles the
cardiovascular response to the elevated metabolic rate during digestion. In fact,
there is an important role of increased histaminergic tone on the heart during
the initial 24 h of digestion in pythons. Whilst the cardiovascular effects of
histamine are well studied in pythons, little is known about the effects in other
groups of reptiles. The histaminergic effects on the heart vary among species and
histamine may exert either pressor and depressor effects by causing either
constrictive or dilatory vascular responses. Here, we investigated the
cardiovascular effects of histamine in three species of reptiles with very
different cardiovascular and pulmonary morphologies. Experiments were performed
on both anesthetized and recovered animals. We show a species-dependent effect of
histamine on the systemic vasculature with dilation in rattlesnakes and
constriction in turtles and caimans but no effect on the pulmonary circulation.
The histamine-induced dilation in rattlesnakes was mediated through an activation
of H2-receptors, whereas the histamine-induced constriction in caimans was
mediated through both adrenergic signaling and H1-receptors activation. In all
three species, histamine-induced tachycardia by direct stimulation of
histaminergic receptors as well as an indirect activation of adrenoreceptors.
This finding highlights a more complex mechanism underlying the action of
histamine than previously recognized in reptiles.
PMID- 28695273
TI - In reply to the letter to the Editor, "Morphological evaluation of median nerve:
why ultrasound?"
PMID- 28695274
TI - Real-world clinical experience of biological disease modifying anti-rheumatic
drugs in Malaysia rheumatoid arthritis patients.
AB - The effect of biologic disease modifying anti-rheumatic drugs (bDMARDs) in
treating rheumatoid arthritis (RA) in real-world clinical practice remains
unknown in Southeast Asia. We aimed to assess the efficacy and safety of bDMARDs
among Malaysian RA patients treated in routine clinical practice. A retrospective
medical chart review of RA patients from 11 government hospitals were conducted
from January 2003 to January 2014. A standardized questionnaire was used to
abstract patient's demographic, clinical and treatment data. Level of disease
activity was measured by DAS28 collected at baseline, 3, 6 and 12 months. Three
hundred and one patients were available for analysis, mean age 41 (SD, 10.8)
years, mean RA duration 12.3 (SD, 6.9) years and 98% had history of two or more
conventional-synthetic DMARDs. There were 467 bDMARD courses prescribed with mean
bDMARDs duration use of 12.9 months (SD 14.7). Tumour necrosis factor alpha
inhibitors were the most common prescribed bDMARDs (77.1%), followed by
Tocilizumab (14.6%) and Rituximab (8.4%). We observed significant improvement in
mean DAS28 values from baseline to 3, 6 and 12 months (p < 0.001). Overall, 16.9%
achieved DAS28 remission at 6 months. A third (35.6%) of patients reported
adverse events, three commonest being infections (46.5%), allergy (22.9%) and
laboratory abnormalities (12.9%). 3.7% of our patients had tuberculosis. Biologic
DMARDs were effective in treating RA in real-world practice in Malaysia, despite
a lower remission rate compared to developed countries. Except for higher rates
of tuberculosis, the AEs were similar to the published reports.
PMID- 28695275
TI - Invasive intramedullary melanotic schwannoma: case report and review of the
literature.
AB - PURPOSE: Melanotic schwannoma (MS) is rare, accounting for less than 1% of
primary peripheral nerve sheath tumors, and most often occurs in the paraspinal
nerve roots. Intramedullary MS is exceedingly rare, and to the best of our
knowledge, only nine cases have been reported in literature. METHODS AND RESULTS:
We present a 47-year-old male, who underwent excision of thoracic intraspinal
space-occupying lesion 6 years ago, as the 10th known case to date of intradural
intramedullary MS that had a more invasive growth pattern than those reported
before, and we review the diagnosis, clinicopathologic features, treatment and
prognosis of intramedullary MS. CONCLUSIONS: Intramedullary MS' behavior is
unpredictable and can have an aggressive clinical course such as recurrence and
metastasis.
PMID- 28695276
TI - Complete genome sequence of rice virus A, a new member of the family
Tombusviridae.
AB - An evaluation of the virus population in rice plants using next-generation
sequencing technologies resulted in the discovery of a new RNA virus, tentatively
named rice virus A (RVA). The complete RVA genome sequence was determined and
analyzed, revealing a genome organization resembling that of viruses classified
in the genera Aureusvirus, Tombusvirus and Zeavirus within the family
Tombusviridae. With 4,832 nucleotides, the RVA genome may be the largest
monopartite genome sequenced to date in the family Tombusviridae. The 453-amino
acid RVA coat protein shares the highest identity with the gp3 protein of an
unclassified carascovirus, SF1 (GenBank accession no. KF510027) isolated from San
Francisco wastewater, rather than the coat protein of any known member of the
family Tombusviridae. These novel characteristics represent a significant
divergence from the genomes of viruses belonging to the sixteen existing genera
of the family Tombusviridae, demonstrating that RVA is likely a new family
member.
PMID- 28695277
TI - Molecular movement in the Arabidopsis thaliana female gametophyte.
AB - KEY MESSAGE: Size limits on molecular movement among female gametes. Cellular
decisions can be influenced by information communicated from neighboring cells.
Communication can occur via signaling or through the direct transfer of
molecules. Movement of RNAs and proteins has frequently been observed among
symplastically connected plant cells. In flowering plants, the female gametes,
the egg cell and central cell, are closely apposed within the female gametophyte.
Here we investigated the ability of fluorescently labeled dyes and small RNAs to
move from the Arabidopsis thaliana central cell to the egg apparatus following
microinjection. These results define a size limit of at least 20 kDa for
symplastic movement between the two gametes, somewhat larger than that previously
observed in Torenia fournieri. Our results indicate that symplastic connectivity
in Arabidopsis thaliana changes after fertilization and suggest that prior to
fertilization mechanisms are in place to facilitate small RNA movement from the
central cell to the egg cell and synergids.
PMID- 28695278
TI - Which temporal resolution to consider when investigating the impact of climatic
data on population dynamics? The case of the lesser horseshoe bat (Rhinolophus
hipposideros).
AB - Climatic variables are often considered when studying environmental impacts on
population dynamics of terrestrial species. However, the temporal resolution
considered varies depending on studies, even among studies of the same taxa. Most
studies interested in climatic impacts on populations tend to average climatic
data across timeframes covering life cycle periods of the organism in question or
longer, even though most climatic databases provide at least a monthly
resolution. We explored the impact of climatic variables on lesser horseshoe bat
(Rhinolophus hipposideros) demography based on count data collected at 94
maternity colonies from 2000 to 2014 in Britanny, France. Meteorological data
were considered using different time resolutions (month, life cycle period and
year) to investigate their adequacy. Model averaging was used to detect
significant predictors for each temporal resolution. Our results show that the
finest temporal resolution, e.g. month, was more informative than coarser ones.
Precipitation predictors were particularly decisive, with a negative impact on
colony sizes when rainfall occurred in October, and a positive impact for June
precipitations. Fecundity was influenced by April weather. This highlights the
strong impact of climatic conditions during crucial but short time periods on the
population dynamics of bats. We demonstrate the importance of choosing an
appropriate time resolution and suggest that analogous studies should consider
fine-scale temporal resolution (e.g. month) to better grasp the relationship
between population dynamics and climatic conditions.
PMID- 28695279
TI - Epigenetic regulation of neural stem cell differentiation towards spinal cord
regeneration.
AB - Severe spinal cord injury (SCI) leads to almost complete neural cell loss at the
injured site, causing the irreversible disruption of neuronal circuits. The
transplantation of neural stem or precursor cells (NS/PCs) has been regarded as
potentially effective for SCI treatment because NS/PCs can compensate for the
injured sites by differentiating into neurons and glial cells (astrocytes and
oligodendrocytes). An understanding of the molecular mechanisms that regulate the
proliferation, fate specification and maturation of NS/PCs and their progeny
would facilitate the establishment of better therapeutic strategies for
regeneration after SCI. In recent years, several studies of SCI animal models
have demonstrated that the modulation of specific epigenetic marks by histone
modifiers and non-coding RNAs directs the setting of favorable cellular
environments that promote the neuronal differentiation of NS/PCs and/or the
elongation of the axons of the surviving neurons at the injured sites. In this
review, we provide an overview of recent progress in the epigenetic
regulation/manipulation of neural cells for the treatment of SCI.
PMID- 28695280
TI - Effect of post-weaning isolation on anxiety- and depressive-like behaviors of
C57BL/6J mice.
AB - Effects of post-weaning isolation on depressive- and anxiety-like behaviors in
rodents have been well studied in the past. However, few studies included both
sexes in a single experiment to study the sex difference in this animal model.
The present study investigated the effect of post-weaning isolation on anxiety-
and depressive-like behaviors in both male and female C57BL/6 J mice. Mice were
individually or grouped housed from postnatal day 21 for 5 weeks until behavioral
tests began. The results showed that social isolation resulted in increased
anxiety in the open field. Isolated-reared female, but not male mice showed an
increased transition between two compartments in the light-dark box and a
decreased immobile time in the forced swim test. We conclude that post-weaning
isolation has a sex-specific effect on emotional behaviors.
PMID- 28695281
TI - Foreword: Immunogenetics special issue 2017.
PMID- 28695282
TI - Host genetic variation and HIV disease: from mapping to mechanism.
AB - This review aims to provide a summary of current knowledge of host genetic
effects on human immunodeficiency virus (HIV) disease. Mapping of simple single
nucleotide polymorphisms (SNP) has been largely successful in HIV, but more
complex genetic associations involving haplotypic or epigenetic variation, for
example, remain elusive. Mechanistic insights explaining SNP associations are
incomplete, but continue to be forthcoming. The number of robust immunogenetic
correlates of HIV is modest and their discovery mostly predates the genome-wide
era. Nevertheless, genome-wide evaluations have nicely validated the impact of
HLA and CCR5 variants on HIV disease, and importantly, made clear the many false
positive associations that were previously suggested by studies using the
candidate gene approach. We describe how multiple HIV outcome measures such as
acquisition, viral control, and immune decline have been studied in adults and in
children, but that collectively these identify only the two replicable loci
responsible for modifying HIV disease, CCR5, and HLA. Recent heritability
estimates in this disease corroborate the modest impact of genetic determinants
and their oligogenic nature. While the mechanism of protection afforded by
genetic variants that diminish CCR5 expression is clear, new aspects of HLA class
I-mediated protection continue to be uncovered. We describe how these genetic
findings have enhanced insights into immunobiology, been clinically translated
into CCR5 antagonists, allowed prioritization of antigens for vaccination
efforts, and identified targets for genome-editing interventions. Finally, we
describe how studies of genetically complex parts of the genome using new tools
may begin revealing additional correlates.
PMID- 28695283
TI - AIDS in chimpanzees: the role of MHC genes.
AB - The ancestral progenitor of common chimpanzees and bonobos experienced a
selective sweep that ravaged its major histocompatibility complex (MHC) class I
repertoire. The causative agent was probably an ancestral retrovirus, highly
related to the contemporary HIV-1 strain, which initiated the acquired
immunodeficiency syndrome pandemic in the human population. As a direct result,
MHC class I allotypes with the capability of targeting conserved retroviral
elements were enriched in the ancestral progenitor. Even today, the impact can be
traced back by studying the functional capacities of the contemporary MHC class I
allotypes of common chimpanzees. Viruses, however, have developed several
strategies to manipulate the cell-surface expression of MHC class I genes.
Monitoring the presence and absence of the MHC class I allotypes on the cell
surface is conducted, for instance, by the hosts' gene products of the killer
cell immunoglobulin-like receptor (KIR) complex. Hence, one may wonder whether-in
the future-any clues with regard to the signature of the MHC class I selective
sweep might be unearthed for the KIR genes as well.
PMID- 28695284
TI - MHC and adaptive immunity in teleost fishes.
AB - The adaptive immune system has long been considered a key evolutionary innovation
of the vertebrates, the product of two rounds of genome duplication that gave
rise to the raw material necessary for the evolution of a highly specific immune
response and immune memory. While comparative studies of a small number of model
organisms have led to the commonly held view that the adaptive immune system has
remained relatively static since its origin, recent studies of non-model
organisms are challenging this notion, highlighting the fact that we have only
begun to scratch the surface in terms of our understanding of immune system
diversity. Some of the most exciting recent results have come from the
comparative analysis of teleost fishes, a group that includes more than 40% of
vertebrates, and shows remarkable diversity in immune system structure and
function. Despite the repeated loss of key components of the adaptive immune
machinery in this group, affected species are capable of mounting a robust
response to immune challenge, suggesting that they have evolved alternative
mechanisms of immune protection. Such deviations from the canonical model of
vertebrate immunity create opportunities to explore common paradigms of immune
function, and may contribute to new experimental approaches and methods of
treatment.
PMID- 28695285
TI - The role of HLA genes in pharmacogenomics: unravelling HLA associated adverse
drug reactions.
AB - Genetic polymorphism in the genes encoding the human leukocyte antigen (HLA)
molecules enables presentation of a wide range peptide ligands thus maximising
immune surveillance of pathogens. A consequence of the diversification of the HLA
Ag-binding pocket is the enhanced opportunity for off-target binding of small
drugs by HLA molecules, with subsequent immune reactivity. These potential off
target interactions are 'set up' to generate T cell-mediated adverse drug
reactions even though the precise mechanisms of most HLA-drug interactions are
still poorly understood. The association between abacavir hypersensitivity
syndrome and HLA-B*57:01 is one exception that has been resolved at a molecular
and mechanistic level. Here, we explore the road to understanding the interaction
between abacavir and the HLA-B*57:01 molecule and review the current state of
understanding of interactions between other drugs and HLA molecules implicated in
adverse drug reactions, which appear to involve multiple mechanisms. The
continued expansion of the pharmacopoeia generates an imperative to understand
these interactions at the molecular level in order to prevent the continued
burden on individuals and the health care system.
PMID- 28695286
TI - The roles of MHC class II genes and post-translational modification in celiac
disease.
AB - Our increasing understanding of the etiology of celiac disease, previously
considered a simple food hypersensitivity disorder caused by an immune response
to cereal gluten proteins, challenges established concepts of autoimmunity. HLA
is a chief genetic determinant, and certain HLA-DQ allotypes predispose to the
disease by presenting posttranslationally modified (deamidated) gluten peptides
to CD4+ T cells. The deamidation of gluten peptides is mediated by
transglutaminase 2. Strikingly, celiac disease patients generate highly disease
specific autoantibodies to the transglutaminase 2 enzyme. The dual role of
transglutaminase 2 in celiac disease is hardly coincidental. This paper reviews
the genetic mapping and involvement of MHC class II genes in disease
pathogenesis, and discusses the evidence that MHC class II genes, via the
involvement of transglutaminase 2, influence the generation of celiac disease
specific autoantibodies.
PMID- 28695287
TI - The role of KIR and HLA interactions in pregnancy complications.
AB - Combinations of KIR and HLA genes associate with pregnancy complications as well
as with many other clinical scenarios. Understanding how certain KIR and HLA
genes influence the biology of a disease is, however, a formidable challenge.
These are the two most variable gene families in the human genome. Moreover, the
biology of a disease is best understood by studying the cells of the affected
tissue. Natural Killer (NK) cells express KIR and are the most abundant
leukocytes in the uterus. Most of our knowledge of NK cells is based on what we
have learned from cells isolated from blood, but these are different from their
tissue resident counterparts, including uterine NK (uNK) cells. Reproductive
immunology faces an additional challenge: Two genotypes must be considered
because both maternal and foetal HLA class I molecules may influence the outcome
of pregnancy, most likely through interactions with maternal KIR expressed on uNK
cells. Maternal uNK cells are not spontaneously cytotoxic and instead engage in
interactions with trophoblast. We hypothesise that these interactions regulate
allocation of resources between the foetus and the mother and may go wrong in
diseases of pregnancy.
PMID- 28695288
TI - Introduction: MHC/KIR and governance of specificity.
AB - The MHC controls specificity, to ensure that appropriate immune responses are
mounted to invading pathogens whilst maintaining tolerance to the host. It
encodes molecules that act as sentinels, providing a snapshot of the health of
the interior and exterior of the cell for immune surveillance. To maintain the
ability to respond appropriately to any disease requires a delicate balance of
expression and function, and many subtleties of the system have been described at
the gene, individual and population level. The main players are the highly
polymorphic classical MHC class I and class II molecules, as well as some non
classical loci of both types. Transporter associated with antigen processing
(TAP) peptide transporters, proteasome components and Tapasin, encoded within the
MHC, are also involved in selection of peptide for presentation. The plethora of
mechanisms microorganisms use to subvert immune recognition, through blocking
these antigen processing and presentation pathways, attests to the importance of
HLA in resistance to infection. There is continued interest in MHC genetics in
its own right, as well as in relation to KIR, to transplantation, infection,
autoimmunity and reproduction. Also of topical interest, cancer immunotherapy
through checkpoint inhibition depends on highly specific recognition of cancer
peptide antigen and continued expression of HLA molecules. Here, we briefly
introduce some background to the MHC/KIR axis in man. This special issue of
immunogenetics expands on these topics, in humans and other model species.
PMID- 28695289
TI - The role of MHC class I gene products in SIV infection of macaques.
AB - Human immunodeficiency virus (HIV) remains among the most significant public
health threats worldwide. Despite three decades of research following the
discovery of HIV, a preventive vaccine remains elusive. The study of HIV elite
controllers has been crucial to elaborate the genetic and immunologic
determinants that underlie control of HIV replication. Coordinated studies of
elite control in humans have, however, been limited by variability among
infecting viral strains, host genotype, and the uncertainty of the timing and
route of infection. In this review, we discuss the role of nonhuman primate (NHP)
models for the elucidation of the immunologic correlates that underlie control of
AIDS virus replication. We discuss the importance of major histocompatibility
complex class I (MHC-I) alleles in activating CD8+ T-cell populations that
promote control of both HIV and simian immunodeficiency virus (SIV) replication.
Provocatively, we make the argument that T-cell subsets recognizing the HIV/SIV
viral infectivity factor (Vif) protein may be crucial for control of viral
replication. We hope that this review demonstrates how an in-depth understanding
of the MHC-I gene products associated with elite control of HIV/SIV, and the
epitopes that they present, can provide researchers with a glimpse into the
protective immune responses that underlie AIDS nonprogression.
PMID- 28695290
TI - Major histocompatibility complex variation and the evolution of resistance to
amphibian chytridiomycosis.
AB - Chytridiomycosis, caused by the fungal pathogen Batrachochytrium dendrobatidis
(Bd), has been implicated in population declines and species extinctions of
amphibians around the world. Susceptibility to the disease varies both within and
among species, most likely attributable to heritable immunogenetic variation.
Analyses of transcriptional expression in hosts following their infection by Bd
reveal complex responses. Species resistant to Bd generally show evidence of
stronger innate and adaptive immune system responses. Major histocompatibility
complex (MHC) class I and class II genes of some susceptible species are up
regulated following host infection by Bd, but resistant species show no
comparable changes in transcriptional expression. Bd-resistant species share
similar pocket conformations within the MHC-II antigen-binding groove. Among
susceptible species, survivors of epizootics bear alleles encoding these
conformations. Individuals with homozygous resistance alleles appear to benefit
by enhanced resistance, especially in environmental conditions that promote
pathogen virulence. Subjects that are repeatedly infected and subsequently
cleared of Bd can develop an acquired immune response to the pathogen. Strong
directional selection for MHC alleles that encode resistance to Bd may deplete
genetic variation necessary to respond to other pathogens. Resistance to
chytridiomycosis incurs life-history costs that require further study.
PMID- 28695291
TI - Missing or altered self: human NK cell receptors that recognize HLA-C.
AB - Natural killer (NK) cells are fast-acting and versatile lymphocytes that are
critical effectors of innate immunity, adaptive immunity, and placental
development. Controlling NK cell function are the interactions between killer
cell immunoglobulin-like receptors (KIRs) and their HLA-A, HLA-B and HLA-C
ligands. Due to the extensive polymorphism of both KIR and HLA class I, these
interactions are highly diversified and specific combinations correlate with
protection or susceptibility to a range of infectious, autoimmune, and
reproductive disorders. Evolutionary, genetic, and functional studies are
consistent with the interactions between KIR and HLA-C being the dominant control
mechanism of human NK cells. In addition to their recognition of the C1 and C2
epitopes, increasing evidence points to KIR having a previously unrecognized
selectivity for the peptide presented by HLA-C. This selectivity appears to be a
conserved feature of activating KIR and may partly explain the slow progress made
in identifying their HLA class I ligands. The peptide selectivity of KIR allows
NK cells to respond, not only to changes in the surface expression of HLA-C, but
also to the more subtle changes in the HLA-C peptidome, such as occur during
viral infection and malignant transformation. Here, we review recent advances in
understanding of human-specific KIR evolution and how the inhibitory and
activating HLA-C receptors allow NK cells to respond to healthy cells, diseased
cells, and the semi-allogeneic cells of the fetus.
PMID- 28695292
TI - Specificity of inhibitory KIRs enables NK cells to detect changes in an altered
peptide environment.
AB - The activity of natural killer (NK) cells is tightly regulated by inhibitory and
activating receptors. Inhibitory killer immunoglobulin-like receptors (iKIRs)
survey the surface of target cells by monitoring the expression of human
leukocyte antigen (HLA) class I. The binding of iKIRs has been shown to be
sensitive to the peptides presented by HLA class I, implying that iKIRs have the
ability to detect the changes in the repertoire of peptide-HLA class I complexes
(pHLA), a process occurring during viral infection and in tumor cells. To study
how the pHLA repertoire changes upon infection, and whether an iKIR is able to
detect these changes, we study peptides eluted from cells prior and after
infection with measles virus (MV). Remarkably, most changes in the repertoire of
potential iKIR ligands are predicted to be caused by the altered expression of
self-peptides. We show that an iKIR can detect these changes in the presented
peptides only if it is sufficiently specific, e.g., if iKIRs can distinguish
between different amino acids in the contact residues (e.g., position 7 and 8).
Our analysis further indicates that one single iKIR per host is not sufficient to
detect changes in the peptide repertoire, suggesting that a multigene family
encoding for different iKIRs is required for successful peptide recognition.
PMID- 28695293
TI - HLA class II and rheumatoid arthritis: the bumpy road of revelation.
AB - Rheumatoid arthritis (RA) is a chronic auto-immune disease primarily targeting
the joints. Approximately 1% of the population is affected by RA, and despite the
improvements in therapeutic interventions, elucidation of the disease
pathogenesis is still in its infancy. RA patients can be subdivided on basis of
the presence of autoantibodies, especially anti-citrullinated protein antibodies
(ACPA). ACPA+ and ACPA- disease most likely differ in aetiology, as different
genetic and environmental risk factors are associated with these two disease
entities. For ACPA+ RA disease, the genetic factors associating with disease
mainly comprised of human leukocyte antigen (HLA) class II molecules. The
predisposing HLA-DR alleles have been depicted as the 'HLA Shared Epitope (SE)
alleles', as these alleles encode a similar sequence, the shared epitope
sequence, within the beta chain of the HLA-DR molecule. In addition to the
involvement of the HLA-SE alleles in the development of ACPA+ RA disease, other
HLA-DR molecules have been shown to confer protection against this disease
entity. The protective HLA molecules have, instead of the SE-motif, a different
but shared sequence at the same location in the beta chain of HLA-DR molecules,
consisting of the amino acid residues DERAA. The possible contributions of the
predisposing and protective HLA molecules in association with ACPA-positive RA
are discussed in this review.
PMID- 28695294
TI - The role of MHC genes in contagious cancer: the story of Tasmanian devils.
AB - The Tasmanian devil, a marsupial species endemic to the island of Tasmania,
harbours two contagious cancers, Devil Facial Tumour 1 (DFT1) and Devil Facial
Tumour 2 (DFT2). These cancers pass between individuals in the population via the
direct transfer of tumour cells, resulting in the growth of large tumours around
the face and neck of affected animals. While these cancers are rare, a contagious
cancer also exists in dogs and five contagious cancers circulate in bivalves. The
ability of tumour cells to emerge and transmit in mammals is surprising as these
cells are an allograft and should be rejected due to incompatibility between
Major Histocompatibility Complex (MHC) genes. As such, considerable research has
focused on understanding how DFT1 cells evade the host immune system with
particular reference to MHC molecules. This review evaluates the role that MHC
class I expression and genotype plays in allowing DFT1 to circumvent
histocompatibility barriers in Tasmanian devils. We also examine recent research
that suggests that Tasmanian devils can mount an immune response to DFT1 and may
form the basis of a protective vaccine against the tumour.
PMID- 28695295
TI - Prioritized Identification of Attractive and Romantic Partner Faces in Rapid
Serial Visual Presentation.
AB - People are sensitive to facial attractiveness because it is an important
biological and social signal. As such, our perceptual and attentional system
seems biased toward attractive faces. We tested whether attractive faces capture
attention and enhance memory access in an involuntary manner using a dual-task
rapid serial visual presentation (dtRSVP) paradigm, wherein multiple faces were
successively presented for 120 ms. In Experiment 1, participants (N = 26) were
required to identify two female faces embedded in a stream of animal faces as
distractors. The results revealed that identification of the second female target
(T2) was better when it was attractive compared to neutral or unattractive. In
Experiment 2, we investigated whether perceived attractiveness affects T2
identification (N = 27). To this end, we performed another dtRSVP task involving
participants in a romantic partnership with the opposite sex, wherein T2 was
their romantic partner's face. The results demonstrated that a romantic partner's
face was correctly identified more often than was the face of a friend or unknown
person. Furthermore, the greater the intensity of passionate love participants
felt for their partner (as measured by the Passionate Love Scale), the more often
they correctly identified their partner's face. Our experiments indicate that
attractive and romantic partners' faces facilitate the identification of the
faces in an involuntary manner.
PMID- 28695296
TI - Women's Work, Gender Roles, and Intimate Partner Violence in Nigeria.
AB - The purpose of this study was to determine the contribution of women's labor
force participation to the risk of intimate partner violence (IPV) victimization
in the past 12 months, using data for 20,635 currently married women aged 15-49
years from the 2013 nationally representative Nigeria Demographic and Health
Survey. Multilevel logistic regression models of sexual and physical IPV, with
interactions between women's work and social norms regarding traditional gender
roles, were developed. Approximately 23% of women aged 15-49 years reported IPV
victimization in the past 12 months. Results revealed that non-cash work relative
to unemployment was positively associated with both forms of IPV victimization,
after controlling for other factors. Women's engagement in cash work was
positively correlated with sexual IPV. The positive association between cash work
and physical IPV victimization was significantly larger for women who resided in
localities with greater male approval of wife beating. In localities where
husband-dominated decision making was more common, a spousal education gap that
favored husbands was more positively associated with sexual IPV. The findings
call for integrated IPV prevention and economic empowerment programs that
consider gender norms and gender-role beliefs and are adapted to the locality
setting, in order to promote social environments in which women can reap the full
benefits of their economic empowerment.
PMID- 28695298
TI - Letter to the editor: In response to "influence of clinical, societal, and
treatment variables on racial difference in ER-/PR- breast cancer survival" by
Roseland ME, Schwartz K, Ruterbusch JJ, Lamerato L, Krajenta R, Booza J, Simon
MS.
PMID- 28695297
TI - Histiocytic and dendritic cell neoplasms: what have we learnt by studying 67
cases.
AB - Tumors derived from histiocytic and dendritic cells encompass a large and
heterogeneous group of neoplastic and reactive conditions, and their diagnosis is
challenging both for pathologists and clinicians. Diagnosis is based on
morphological and phenotypical findings, but hybrid features are not uncommon.
Furthermore, recent studies uncovered the molecular mechanisms driving some of
these tumors, improving diagnostic adequacy, and providing the basis for
effective therapeutic breakthroughs.Sixty-seven cases were submitted to the
accessory cell and histiocytic neoplasms session at the European Association of
Haematopathology/Society for Hematopathology workshop 2016 held in Basel,
Switzerland. The cases included histiocytic sarcomas (HS), Langerhans cell tumors
(LCT), Erdheim-Chester disease, interdigitating dendritic cell sarcomas (IDCS),
indeterminate dendritic cell tumors (IND-DCT), follicular dendritic cell
sarcomas, and blastic plasmacytoid dendritic cell neoplasms. Rosai-Dorfman
disease and, more rare, conditions such as ALK-positive histiocytosis were also
submitted. These cases illustrated classical and unexpected features at
morphological, phenotypical, and molecular levels, providing a valuable
compendium for pathologists confronting with these tumors.The paper summarizes
the most notable features of every single group of diseases, with comments about
the most challenging issues, in the attempt to provide practical indications for
their recognition.
PMID- 28695299
TI - Adjuvant ovarian suppression for resected breast cancer: 2017 critical
assessment.
AB - Currently available data supporting adjuvant ovarian function suppression for
resected breast cancer in premenopausal women in addition to standard
chemotherapy and tamoxifen are not persuasive, even though an ASCO guideline
supports them. Available information from the key trial, called "SOFT," has only
5-year follow-up in a 15-year disease. It employs breast cancer events as an
endpoint, rather than distant metastases, or better still, death from any cause.
The small advantages reported to date may disappear when aromatase inhibitors are
given after the occurrence of menopause in the control population. Caution should
be exercised in recommending ovarian suppression in all but the highest-risk
situations.
PMID- 28695300
TI - New FTY720-docetaxel nanoparticle therapy overcomes FTY720-induced lymphopenia
and inhibits metastatic breast tumour growth.
AB - PURPOSE: Combining molecular therapies with chemotherapy may offer an improved
clinical outcome for chemoresistant tumours. Sphingosine-1-phosphate (S1P)
receptor antagonist and sphingosine kinase 1 (SK1) inhibitor FTY720 (FTY) has
promising anticancer properties, however, it causes systemic lymphopenia which
impairs its use in cancer patients. In this study, we developed a nanoparticle
(NP) combining docetaxel (DTX) and FTY for enhanced anticancer effect, targeted
tumour delivery and reduced systemic toxicity. METHODS: Docetaxel, FTY and
glucosamine were covalently conjugated to poly(lactic-co-glycolic acid) (PLGA).
NPs were characterised by dynamic light scattering and electron microscopy. The
cellular uptake, cytotoxicity and in vivo antitumor efficacy of CNPs were
evaluated. RESULTS: We show for the first time that in triple negative breast
cancer cells FTY provides chemosensitisation to DTX, allowing a four-fold
reduction in the effective dose. We have encapsulated both drugs in PLGA complex
NPs (CNPs), with narrow size distribution of ~ 100 nm and excellent cancer cell
uptake providing sequential, sustained release of FTY and DTX. In triple negative
breast cancer cells and mouse breast cancer models, CNPs had similar efficacy to
systemic free therapies, but allowed an effective drug dose reduction.
Application of CNPs has significantly reversed chemotherapy side effects such as
weight loss, liver toxicity and, most notably, lymphopenia. CONCLUSIONS: We show
for the first time the DTX chemosensitising effects of FTY in triple negative
breast cancer. We further demonstrate that encapsulation of free drugs in CNPs
can improve targeting, provide low off-target toxicity and most importantly
reduce FTY-induced lymphopenia, offering potential therapeutic use of FTY in
clinical cancer treatment.
PMID- 28695301
TI - Optimal use of anti-EGFR monoclonal antibodies for patients with advanced
colorectal cancer: a meta-analysis.
AB - This meta-analysis was performed to determine the optimal use of anti-EGFR mAb in
the treatment of metastasized colorectal cancer (mCRC). Seventeen randomized
clinical trials were included, all evaluating the added value of anti-EGFR mAb to
standard treatment line in patients with KRAS wild-type mCRC. Hazard and odds
ratios were pooled using a random effect model, weighted according to cohort
size. Pooled data of six first- and two second-line studies demonstrated a
significantly improved ORR (OR 1.62, CI 1.27-2.04; OR 4.78, CI 3.39-6.75,
respectively) and PFS (HR 0.79, CI 0.67-0.94; HR 0.80, CI 0.71-0.91,
respectively) with the addition of anti-EGFR mAb to chemotherapy, while OS
remained similar. Two third-line anti-EGFR mAb monotherapy studies revealed an
improved PFS and OS (HR 0.44, CI 0.35-0.52; HR 0.55, CI 0.41-0.74). Addition of
anti-EGFR versus anti-VEGF mAb to first-line chemotherapy was evaluated in three
studies; ORR and PFS were comparable, while OS was improved (HR 0.8, CI 0.65
0.97). The influence of the chemotherapy backbone on anti-EGFR mAb efficacy,
evaluated with meta-regression, indicated a higher ORR with irinotecan-based
versus oxaliplatin-based regimens, but comparable PFS and OS. Reported toxicity
(>=3 grade) increased ~20% in all treatment lines with the addition of anti-EGFR
mAb. Anti-EGFR treatment significantly improves response and survival outcome of
patients with (K)RAS wild-type mCRC, regardless of treatment line or
chemotherapeutic backbone. Saving anti-EGFR mAb as third-line monotherapy is a
valid and effective option to prevent high treatment burden caused by combination
therapy. Combination treatment with anti-EGFR mAb to achieve radical resection of
metastases needs further investigation.
PMID- 28695302
TI - Argatroban Attenuates Diabetic Cardiomyopathy in Rats by Reducing Fibrosis,
Inflammation, Apoptosis, and Protease-Activated Receptor Expression.
AB - PURPOSE: Chronic diabetes is associated with cardiovascular dysfunctions.
Diabetic cardiomyopathy (DCM) is one of the serious cardiovascular complications
associated with diabetes. Despite significant efforts in understanding the
pathophysiology of DCM, management of DCM is not adequate due to its complex
pathophysiology. Recently, involvement of protease-activated receptors (PARs) has
been postulated in cardiovascular diseases. These receptors are activated by
thrombin, trypsin, or other serine proteases. Expression of PAR has been shown to
be increased in cardiac diseases such as myocardial infarction, viral
myocarditis, and pulmonary arterial hypertension. However, the role of PAR in DCM
has not been elucidated yet. Therefore, in the present study, we have
investigated the role of PAR in the condition of DCM using a pharmacological
approach. We used argatroban, a direct thrombin inhibitor for targeting PAR.
METHODS: Type-2 diabetes mellitus (T2DM) was induced by high-fat feeding along
with low dose streptozotocin (STZ 35 mg/kg, i.p. single dose) in male Sprague
Dawley rats. After 16 weeks of diabetes induction, animals were treated with
argatroban at 0.3 and 1 mg/kg dose daily for 4 weeks. After 20 weeks, ventricular
functions were measured using ventricular catheterization. Cardiac histology,
TUNEL staining, and immunoblotting were performed to evaluate cardiac fibrosis,
DNA fragmentation, and expression level of different proteins, respectively.
RESULTS: T2DM was associated with cardiac structural and functional disturbances
as evidenced from impaired cardiac functional parameters and increased fibrosis.
There was a significant increase in PAR expression after 20 weeks of diabetes
induction. Four weeks argatroban treatment ameliorated metabolic alterations
(reduced plasma glucose and cholesterol), ventricular dysfunctions (improved
systolic and diastolic functions), cardiac fibrosis (reduced percentage area of
collagen in picro-sirius red staining), and apoptosis (reduced TUNEL positive
nuclei). Reduced expression of PAR1 and PAR4 in the argatroban-treated group
indicates a response towards inhibition of thrombin. In addition, AKT (Ser-473),
GSK-3beta (Ser-9), p-65 NFKB phosphorylation, TGF-beta, COX-2, and caspase-3
expression were reduced significantly along with an increase in SERCA expression
in argatroban-treated diabetic rats which indicated the anti-fibrotic, anti
inflammatory, and anti-apoptotic potential of argatroban in DCM. CONCLUSION: This
study suggests the ameliorative effects of argatroban in diabetic cardiomyopathy
by improving ventricular functions and reducing fibrosis, inflammation,
apoptosis, and PAR expression.
PMID- 28695303
TI - A comparison of cosegregation analysis methods for the clinical setting.
AB - Quantitative cosegregation analysis can help evaluate the pathogenicity of
genetic variants. However, genetics professionals without statistical training
often use simple methods, reporting only qualitative findings. We evaluate the
potential utility of quantitative cosegregation in the clinical setting by
comparing three methods. One thousand pedigrees each were simulated for benign
and pathogenic variants in BRCA1 and MLH1 using United States historical
demographic data to produce pedigrees similar to those seen in the clinic. These
pedigrees were analyzed using two robust methods, full likelihood Bayes factors
(FLB) and cosegregation likelihood ratios (CSLR), and a simpler method, counting
meioses. Both FLB and CSLR outperform counting meioses when dealing with
pathogenic variants, though counting meioses is not far behind. For benign
variants, FLB and CSLR greatly outperform as counting meioses is unable to
generate evidence for benign variants. Comparing FLB and CSLR, we find that the
two methods perform similarly, indicating that quantitative results from either
of these methods could be combined in multifactorial calculations. Combining
quantitative information will be important as isolated use of cosegregation in
single families will yield classification for less than 1% of variants. To
encourage wider use of robust cosegregation analysis, we present a website (
http://www.analyze.myvariant.org ) which implements the CSLR, FLB, and Counting
Meioses methods for ATM, BRCA1, BRCA2, CHEK2, MEN1, MLH1, MSH2, MSH6, and PMS2.
We also present an R package, CoSeg, which performs the CSLR analysis on any gene
with user supplied parameters. Future variant classification guidelines should
allow nuanced inclusion of cosegregation evidence against pathogenicity.
PMID- 28695304
TI - Heavy metal contamination in river water and sediments of the Swarnamukhi River
Basin, India: risk assessment and environmental implications.
AB - The concentration of heavy metals was analyzed each of 20 river water, suspended
sediments and bed sediments along the stretch of Swarnamukhi River Basin. River
water is not contaminated with heavy metals except Fe and Mn. Contamination
factor in sediments shows considerable to very high degree contamination with Cr,
Cu, Pb and Zn. The sources of these metals could be residential wastes, sewer
outfall, fertilizers, pesticides (M-45 + carbondine) and traffic activities apart
from natural weathering of granitic rocks present in the basin area. Principal
component analyses indicate the interaction between metals in different media.
The comparison of metals (Cu, Pb and Zn) in bed sediments of Swarnamukhi River
with the Indian and world averages indicates that the values obtained in the
basin are above the Indian averages and far below to the world averages. Average
shale values and sediment quality guidelines point toward the enrichment and
contamination of Cu, Cr, Pb and Zn to several fold leading to eco-toxicological
risks in basin.
PMID- 28695305
TI - Mercury contamination in selected foodstuffs and potential health risk assessment
along the artisanal gold mining, Gilgit-Baltistan, Pakistan.
AB - This study investigates the mercury (Hg) contaminations in soil and foodstuffs
along the artisanal gold mining areas, Gilgit-Baltistan Province, Pakistan. For
this purpose, soils were analyzed for Hg concentrations and evaluated for the
enrichment/contamination using enrichment factor or contamination factors (CF).
The CF values ranged from 18.9 to 153 showed multifold higher levels of Hg
contamination as compared to background or reference site. Foodstuffs including
vegetables, seeds or grains and fish muscles showed Hg accumulation. Results
revealed that Hg concentrations in foodstuffs were higher than the critical human
health value set by European Union. The Hg in foodstuffs was consumed and,
therefore, evaluated for the risk assessment indices using the daily intake (DI)
and health risk index (HRI) for the exposed human population both children and
adults. Results of this study revealed that cumulative HRI values through
foodstuffs consumption were <1 (within safe limit), but if the current practices
continued, then the Hg contamination could pose potential threat to exposed
population in near future.
PMID- 28695306
TI - Erratum to: Viral load of EBV DNAemia is a predictor of EBV-related post
transplant lymphoproliferative disorders in pediatric renal transplant
recipients.
PMID- 28695307
TI - Comments on Chavent et al.: Renovascular hypertension: results in adulthood of
renal autotransplantation performed in children.
PMID- 28695308
TI - Renovascular hypertension: results in adulthood of renal autotransplantation
performed in children-response to comments by Della Schiava and Lermusiaux.
PMID- 28695309
TI - Empruthotrema longipenis n. sp. (Monogenoidea: Monocotylidae: Merizocotylinae)
from the olfactory sacs of the smooth butterfly ray Gymnura micrura (Bloch &
Schneider) (Myliobatiformes: Gymnuridae) in the Gulf of Mexico.
AB - A new species of Empruthotrema Johnston & Tiegs, 1922 is described based on
specimens collected from the olfactory sacs of smooth butterfly rays Gymnura
micrura (Bloch & Schneider) captured in Mobile Bay (northcentral Gulf of Mexico),
Alabama, USA. Empruthotrema longipenis n. sp. is most similar to the type-species
Empruthotrema raiae (MacCallum, 1916) Johnston & Tiegs, 1922 by having 12
marginal and two interhamular loculi with members of haptoral hook pair 1 located
midway along the periphery of each interhamular loculus and those of hook pair 2
located at the marginal termini of the bilateral septa flanking the interhamular
loculi. Empruthotrema longipenis n. sp. differs from E. raiae by having a much
longer male copulatory organ and from its remaining congeners by the sinistral
and extracecal ejaculatory bulb flanking the pharynx, the number of interhamular
and marginal septa, and the distribution of hook pairs 1 and 2 along the haptoral
margin. This is the first report of a monocotylid from the smooth butterfly ray
and from Mobile Bay. The diversity of haptoral morphotypes among the currently
accepted species of Empruthotrema is detailed and discussed in the context of
monophyly of the genus.
PMID- 28695310
TI - Central aortic pulse pressure, thrombogenicity and cardiovascular risk.
AB - High central aortic pulse pressure (CPP) and thrombin-induced platelet-fibrin
clot strength (TIP-FCS) have been associated with ischemic outcomes in patients
with coronary artery disease in separate studies. But, the ischemic risk
associated with these factors has never been analyzed in a single study and their
interrelation is unknown. The primary aim of the study was to establish cut
points for CPP and TIP-FCS measured at the time of catheterization associated
with long term major adverse cardiovascular events. We enrolled 334 consecutive
patients undergoing cardiac catheterization and assessed thrombogenicity by
thrombelastography. Patients were followed up to 3 years. The primary endpoint
was a composite of cardiovascular death, myocardial infarction, and ischemic
stroke and the secondary endpoint was occurrence of the primary endpoint or
recurrent ischemic events requiring hospitalization. Patients with primary and
secondary endpoint occurrence had higher CPP (83 +/- 20 vs. 60 +/- 18 mmHg, p <
0.0001; 70 +/- 21 vs. 59 +/- 18 mmHg, p < 0.0001, respectively) and TIP-FCS (68.5
+/- 5.8 vs. 65.5 +/- 5.0 mm, p = 0.008; 67.4 +/- 5.9 vs. 65.2 +/- 4.8 mm, p =
0.001, respectively). CPP >60 mmHg and TIP-FCS >69 mm were both independent
predictors of primary endpoint occurrence (p = 0.0001 and p = 0.02,
respectively). ROC analysis for CPP and TIP-FCS showed a C-statistic of 0.81 (p <
0.0001) and 0.68 (p = 0.007) for the primary endpoint, respectively. Patients
with CPP >60 mmHg had higher TIP-FCS (66.8 +/- 5.1 vs. 64.8 +/- 5.0 mm, p <
0.001) and primary and secondary endpoint occurrence (13 vs. 1.1%, p < 0.0001 and
31.8 vs. 14.4%, p = 0.0002, respectively). CPP >60 mmHg + TIP-FCS > 69 mm was
associated with a markedly increased risk of primary endpoint occurrence [HR (95%
CI) 5.4(2.3-12.5), p = 0.0001]. High CPP and thrombogenicity are interrelated;
each are independently associated with increased cardiovascular risk; and
simultaneous presence markedly enhances risk. The mechanistic link between CPP
and thrombogenicity deserves further study.
PMID- 28695311
TI - Aberrant paramagnetic signals outside the tumor volume on routine surveillance
MRI of brain tumor patients.
AB - Late complications of cerebral radiation therapy (RT) involve vascular injury
with acquired cavernous malformation, telangiectasias and damage to vascular
walls which are well recognized in children. Its incidence in adults is unknown.
Blood products and iron deposition that accompany vascular injury create
paramagnetic effects on MRI. This study retrospectively investigated the
frequency of paramagnetic lesions on routine surveillance MRI of adult brain
tumor patients. MRI studies of 115 brain tumor patients were reviewed. Only
studies containing sequences of either susceptibility weighted images or gradient
echo or blood oxygenation level dependent imaging were included. Lesions inside
the tumor volume were not considered. 68 studies fulfilled the above criteria and
included 48 patients with previous RT (35 followed for >2 years and 13 for 1
year) and 20 patients who were not treated with RT. The median age at time of
irradiation was 47 years. Aberrant paramagnetic lesions were found in 23/35 (65%)
patients followed for >2 years after RT and in only 1/13 (8%) patients followed
for 1-year after radiation (p = 0.03). The 1-year follow-up group did not differ
from the control group [2/20 (9%)]. Most lesions were within the radiation field
and none of the patients had related symptomatology. The number and incidence of
these lesions increased with time and amounted to 75% over 3 years post RT. MRI
paramagnetic signal aberrations are common findings in adult brain tumor patients
that evolve over time after RT. The clinical significance of these lesions needs
further investigation.
PMID- 28695312
TI - Use of biological mesh in trans-anal treatment for recurrent recto-urethral
fistula.
AB - PURPOSE: To report the author's experience on a mini-invasive technique using
bioprosthetic plug and a rectal wall flap advancement in the treatment of
recurrent recto-urethral fistula. MATERIALS AND METHODS: Between 2013 and 2015,
seven patients with recurrent recto-urethral fistula were referred to the
Pederzoli Hospital, Peschiera del Garda, Verona, Italy. Intraoperatively all
patients were found to have a rectal wall lesion and were treated with urinary
and fecal diversion. For the persistence of the fistula, all the patients
underwent a mini-invasive treatment consisting on placement of a bioprosthetic
plug in the fistula covered by an endorectal advancement flap through a trans
anal and trans-urethral combined technique. RESULTS: Median operative time was 48
min with a median blood loss of 30 ml. Median hospital stay was 3 days (IQR 1-3).
No case of fistula recurrence or plug migration was described. None of the
patients experienced fecal or urinary incontinence. All patients obtained
complete fistula healing. CONCLUSIONS: Recurrent recto-urethral fistula is a
challenging postsurgical complication for surgeons and urologists, and its best
treatment is still unknown. Our method seems to be feasible and effective for the
treatment of complex recto-urethral fistula.
PMID- 28695313
TI - Elderly patients with chronic kidney disease have higher risk of
hyperparathyroidism.
AB - PURPOSE: As the world's population ages, the incidence of chronic kidney disease
(CKD) is growing. There is ongoing debate regarding whether high levels of
parathyroid hormone (PTH) would be more common in elderly than young patients,
and which factors are driven the risk of secondary hyperparathyroidism (SHPT),
independent of renal function. METHODS: Elderly patients (age >= 65 years, N =
518) were compared to a 1:1 sex- and estimated glomerular filtration rate (eGFR)
matched sample of young patients (age < 65 years), in a cross-sectional analysis.
Demographic, biochemical and drug prescription data were collected from
electronic charts. The main outcome measure was the prevalence of SHPT, defined
as PTH > 65 pg/mL. RESULTS: Elderly patients presented higher serum calcium and
PTH levels and lower serum phosphate, and were taking more diuretics than young
patients. SHPT was more frequent among elderly patients (49.4 vs. 38.6%, p =
0.005), and it was associated with lower eGFR, low levels of 25(OH) vitamin D and
with furosemide therapy, while thiazide use was a protector factor. Elderly
patients with 25(OH) vitamin D > 40 ng/mL were protected against SHPT. The Ca/PTH
ratio was lower in elderly than in young patients [0.15 (0.10, 0.20) vs. 0.16
(0.11, 0.23), respectively, p = 0.003]. CONCLUSION: CKD elderly patients have
higher risk of SHPT than young, which cannot be explained solely by renal
function. Besides low levels of vitamin D, furosemide therapy and a distinct
relationship between calcium and PTH are possible factors contributing to SHPT.
Whether this is a result of renal resistance to PTH or an altered set point to
calcium deserves further investigation.
PMID- 28695314
TI - Bacterial production and reconstitution in proteoliposomes of Solanum
lycopersicum CAT2: a transporter of basic amino acids and organic cations.
AB - KEY MESSAGE: The vacuolar SlCAT2 was cloned, over-produced in E. coli and
reconstituted in proteoliposomes. Arg, Ornithine and Lys were identified as
substrates. Unexpectedly, also the organic cations Tetraethylammonium and
Acetylcholine were transported indicating involvement of SlCAT2 in signaling. In
land plants several transporters are involved in ion and metabolite flux across
membranes of cells or intracellular organelles. The vacuolar amino acid
transporter CAT2 from Solanum lycopersicum was investigated in this work. SlCAT2
was cloned from tomato flower cDNA, over-produced in Escherichia coli and
purified by Nichel-chelating chromatography. For functional studies, the
transporter was reconstituted in proteoliposomes. Competence of SlCAT2 for Arg
transport was demonstrated measuring uptake of [3H]Arg in proteoliposomes which
was trans-stimulated by internal Arg or ornithine. Uptake of [3H]Ornithine and
[3H]Lys was also detected at lower efficiency with respect to [3H]Arg. Transport
was activated by the presence of intraliposomal ATP suggesting regulation by the
nucleotide. The prototype for organic cations tetraethylammonium (TEA) was also
transported by SlCAT2. However, scarce reciprocal inhibition between TEA and Arg
was found, while the biguanide metformin was able to strongly inhibit uptake of
both substrates. These findings suggest that amino acids and organic cations may
interact with the transporter through different functional groups some of which
are common for the two types of substrates. Interestingly, reconstituted SlCAT2
showed competence for acetylcholine transport, which was also inhibited by
metformin. Kinetics of Arg and Ach transport were performed from which Km values
of 0.29 and 0.79 mM were derived, respectively.
PMID- 28695316
TI - Interobserver variability in target volume delineation of hepatocellular
carcinoma : An analysis of the working group "Stereotactic Radiotherapy" of the
German Society for Radiation Oncology (DEGRO).
AB - BACKGROUND: Definition of gross tumor volume (GTV) in hepatocellular carcinoma
(HCC) requires dedicated imaging in multiple contrast medium phases. The aim of
this study was to evaluate the interobserver agreement (IOA) in gross tumor
delineation of HCC in a multicenter panel. METHODS: The analysis was performed
within the "Stereotactic Radiotherapy" working group of the German Society for
Radiation Oncology (DEGRO). The GTVs of three anonymized HCC cases were
delineated by 16 physicians from nine centers using multiphasic CT scans. In the
first case the tumor was well defined. The second patient had multifocal HCC (one
conglomerate and one peripheral tumor) and was previously treated with
transarterial chemoembolization (TACE). The peripheral lesion was adjacent to the
previous TACE site. The last patient had an extensive HCC with a portal vein
thrombosis (PVT) and an inhomogeneous liver parenchyma due to cirrhosis. The IOA
was evaluated according to Landis and Koch. RESULTS: The IOA for the first case
was excellent (kappa: 0.85); for the second case moderate (kappa: 0.48) for the
peripheral tumor and substantial (kappa: 0.73) for the conglomerate. In the case
of the peripheral tumor the inconsistency is most likely explained by the
necrotic tumor cavity after TACE caudal to the viable tumor. In the last case the
IOA was fair, with a kappa of 0.34, with significant heterogeneity concerning the
borders of the tumor and the PVT. CONCLUSION: The IOA was very good among the
cases were the tumor was well defined. In complex cases, where the tumor did not
show the typical characteristics, or in cases with Lipiodol (Guerbet, Paris,
France) deposits, IOA agreement was compromised.
PMID- 28695315
TI - UBIQUITIN-SPECIFIC PROTEASES function in plant development and stress responses.
AB - KEY MESSAGE: UBIQUITIN-SPECIFIC PROTEASES play important roles in plant
development and stress responses. Protein ubiquitination and deubiquitination are
reversible processes, which can modulate the stability, activity as well as
subcellular localization of the substrate proteins. UBIQUITIN-SPECIFIC PROTEASE
(UBP) protein family participates in protein deubiquitination. Members of UBP
family are involved in a variety of physiological processes in plants, as
evidenced by their functional characterization in model plant Arabidopsis and
other plants. UBPs are conserved in plants and distinct UBPs function in
different regulatory processes, although functional redundancies exist between
some members. Here we briefly reviewed recent advances in understanding the
biological functions of UBP protein family in Arabidopsis, particularly the
molecular mechanisms by which UBPs regulate plant development and stress
responses. We believe that elucidation of UBPs function and regulation in
Arabidopsis will provide new insights about protein deubiquitination and might
shed light on the understanding of the mechanistic roles of UBPs in general,
which will definitely contribute to crop improvement in agriculture.
PMID- 28695317
TI - Pre-radiotherapy PSA progression is a negative prognostic factor in prostate
cancer patients using 5-alpha-reductase inhibitors.
AB - OBJECTIVE: To investigate the impact of 5-alpha-reductase inhibitor (5-ARI) use
on radiotherapy outcomes for localized prostate cancer. PATIENTS AND METHODS: We
included 203 patients on a 5-ARI from our institutional database comprising over
2500 patients who had been treated with either external beam radiotherapy (EBRT)
or brachytherapy for localized prostate cancer. Patients received a 5-ARI for
urinary symptoms or active surveillance. Cancer progressions at the time of
definitive treatment were analyzed according to the following criteria: (a)
progression of Gleason score or increase in cancer volume on biopsy, (b) first
biopsy positive for cancer after being treated for urinary symptoms with a 5-ARI,
and (c) prostate-specific antigen (PSA) progression with or without a previous
cancer diagnosis. Biochemical failure (BF) was defined by the Phoenix definition.
Log-rank test was used for survival analysis. RESULTS: At a median follow-up of
38.2 months (standard deviation 22.2 months), 10 (4.9%) patients experienced BF.
Concerning prostate cancer progression criteria, 52% of men demonstrated none,
37% showed only one criterion, and 11% showed two. Using univariate analysis, PSA
progression (p = 0.004) and appearance of a positive biopsy (p < 0.001) were
significant predictive factors for BF, while Gleason progression (p = 0.3) was
not. In multivariate analysis adjusted for cancer aggressiveness, rising PSA
(hazard ratio, HR, 5.7; 95% confidence interval, CI, 1.1-28.8; p = 0.04) and the
number of cancer progression factors (HR 2.9, 95% CI 1.2-7.0, p = 0.02) remained
adverse risk factors. CONCLUSION: PSA progression experienced during 5-ARI
treatment before radiotherapy is predictive of worse biochemical outcome. Such
details should be considered when counseling men prior to radiation therapy.
PMID- 28695318
TI - [Subjective Gait Stability in the Elderly].
AB - BACKGROUND: It can be assumed that the feeling of gait stability or gait
instability in the elderly may be independent of a possible fear of falling or a
history of falling when walking. Up to now, there has been a lack of
spatiotemporal gait parameters for older people who subjectively feel secure when
walking. OBJECTIVE: The aim of the study is to analyse the distribution of
various gait parameters for older people who subjectively feel secure when
walking. MATERIALS AND METHODS: In a cross-sectional study, the gait parameters
stride time, step time, stride length, step length, double support, single
support, and walking speed were measured using a Vicon three-dimensional motion
capture system (Plug-In Gait Lower-Body Marker Set) in 31 healthy people aged 65
years and older (mean age 72 +/- 3.54 years) who subjectively feel secure when
walking. RESULTS: There was a homogeneous distribution in the gait parameters
examined, with no abnormalities. The mean values have a low variance with narrow
confidence intervals. CONCLUSION: This study provides evidence that people who
subjectively feel secure when walking demonstrate similarly objective gait
parameters..
PMID- 28695319
TI - Acute Impact of Selected Pyridoindole Derivatives on Fos Expression in Different
Structures of the Rat Brain.
AB - The impacts of three pyridoindole derivatives (PDs), designated as PD144, PD143,
and PD104, which have previously been shown to have antidepressant (PD144) and
anxiolytic (PD143, PD104) properties, were investigated on the Fos expressions in
11 different rat brain areas, including the medial prefrontal cortex, striatum,
septum, accumbens nucleus (shell, core), bed nucleus of the stria terminalis,
hypothalamic paraventricular nucleus, central amygdala, locus coeruleus, dorsal
raphe nucleus, and the solitary tract nucleus. Control rats received vehicle,
while the other three groups the PDs in a dose of 25 mg/kg/b.w. The animals were
transcardially perfused with a fixative 90 min after the treatments. Coronal
sections of 40-um thickness were processed for Fos-immunostaining by avidin
biotin-peroxidase complex and visualized by nickel-intensified diaminobenzidine
complex. Fos-labeled sections were counterstained with neuropeptides including
corticoliberine (CRH), oxytocin (OXY), vasopressin (AVP), and vasoactive
intestinal polypeptide (VIP) and processed for immunofluorescence staining using
Alexa Fluor 555 dye. In all the three groups of animals, the upregulation of PDs
induced Fos expression only in 2 of 11 brain areas was investigated, namely, in
the hypothalamic paraventricular nucleus (PVN) and the central amygdaloid nucleus
(CeA). The other brain structures studied were devoid of Fos expression.
Counterstaining of the Fos-labeled CeA-containing sections with VIP antibody
revealed that the Fos expression stimulated by the PDs was upregulated in all the
CeA subdivisions (lateral, ventral, capsular), except the medial one. Dual
immunoprocessings showed Fos/CRH-labeling in both the PVN and the amygdala and
Fos/OXY in the PVN. No Fos/AVP colocalizations were seen in the PVN. The obtained
data provide the first view on the intracerebral effects of three new PDs
derivatives, which effects were restricted only to the PVN and CeA areas. The
present data may help to improve our understanding of the impact of the selected
PDs on the brain and to anticipate possible behavioral and neuroendocrine
consequences.
PMID- 28695320
TI - AT1 and AT2 Receptors in the Prelimbic Cortex Modulate the Cardiovascular
Response Evoked by Acute Exposure to Restraint Stress in Rats.
AB - The prelimbic cortex (PL) is an important structure in the neural pathway
integrating stress responses. Brain angiotensin is involved in cardiovascular
control and modulation of stress responses. Blockade of angiotensin receptors has
been reported to reduce stress responses. Acute restraint stress (ARS) is a
stress model, which evokes sustained blood pressure increase, tachycardia, and
reduction in tail temperature. We therefore hypothesized that PL locally
generated angiotensin and angiotensin receptors modulate stress autonomic
responses. To test this hypothesis, we microinjected an angiotensin-converting
enzyme (ACE) inhibitor or angiotensin antagonists into the PL, prior to ARS. Male
Wistar rats were used; guide cannulas were bilaterally implanted in the PL for
microinjection of vehicle or drugs. A polyethylene catheter was introduced into
the femoral artery to record cardiovascular parameters. Tail temperature was
measured using a thermal camera. ARS was started 10 min after PL treatment with
drugs. Pretreatment with ACE inhibitor lisinopril (0.5 nmol/100 nL) reduced the
pressor response, but did not affect ARS-evoked tachycardia. At a dose of 1
nmol/100 nL, it reduced both ARS pressor and tachycardic responses. Pretreatment
with candesartan, AT1 receptor antagonist reduced ARS-evoked pressor response,
but not tachycardia. Pretreatment with PD123177, AT2 receptor antagonist, reduced
tachycardia, but did not affect ARS pressor response. No treatment affected ARS
fall in tail temperature. Results suggest involvement of PL angiotensin in the
mediation of ARS cardiovascular responses, with participation of both AT1 and AT2
receptors. In conclusion, results indicate that PL AT1-receptors modulate the ARS
evoked pressor response, while AT2-receptors modulate the tachycardic component
of the autonomic response.
PMID- 28695321
TI - Angiogenesis and Lymphangiogenesis in the Adrenocortical Tumors.
AB - Adrenocortical tumors (ACT) are common adrenal tumors. The majority of ACTs are
non-functioning and benign, while adrenocortical carcinomas (ACC) are rare,
usually very aggressive and often metastasized when first diagnosed. Our aim was
to assess whether blood and lymph vessel density within ACTs correlate with the
malignancy character or tumor functionality. For that, the microvascular
distribution was evaluated by immunohistochemistry staining with D2-40 antibody,
for lymph vessels and CD-31 antibody, for blood vessels, in ACCs (n = 15),
adenomas with Cushing syndrome (n = 9) and non-functioning adenomas (n = 10). The
percentage of stained area was quantified by computerized morphometric analysis.
D2-40 expression was significantly lower in ACC as compared to adenomas with
Cushing syndrome (p < 0.01) and correlated positively with the expression of the
steroidogenic acute regulatory protein (StAR) (R2 = 0.553, p < 0.001). CD31
expression was found to be significantly higher in ACC as compared to adenomas
with Cushing syndrome (p < 0.05). Our results show that angiogenesis is increased
in ACC, suggesting that this phenomenon may have an important role in ACT
biological behavior, while lymph vascular density seems to be more closely
related to the tumor functional status than malignancy.
PMID- 28695322
TI - The Tumor Entity Denominated "clear cell-papillary renal cell carcinoma"
According to the WHO 2016 new Classification, have the Clinical Characters of a
Renal Cell Adenoma as does Harbor a Benign Outcome.
AB - The new WHO 2016 classification of renal neoplasia encounters the new entity
called "clear cell papillary renal cell carcinoma" (ccpRCC). The ccpRCC has been
long included as a subtype of clear cell RCC histotype and it actually ranges
from 2 to 9% in different routinely available cohort of renal carcinomas. Of
important note, ccpRCC does not show any recurrences or metastases or lymph-node
invasion and the outcome is always good. We reviewed twenty-four publications
with available follow-up for patients (no. 362) affected by clear cell papillary
RCCs/renal adenomatoid tumours and notably ccpRCC harbors an indolent clinical
behavior after a mean of 38 months (3,5 years) of follow-up. This paper reviews
the histological, molecular and clinical features characterizing ccpRCC, with the
goal of focusing the knowledge of the benign fashion of this new tumour entity,
supporting the idea of a new renal cell adenoma recruited morphologically from ex
conventional clear cell RCC tumours.
PMID- 28695324
TI - The effect of almonds on vitamin E status and cardiovascular risk factors in
Korean adults: a randomized clinical trial.
AB - PURPOSE: Almonds have shown to beneficially modify some cardiovascular risk
factors in clinical trials conducted in diverse ethnic populations but this
relationship has never been tested in Koreans. Thus, we tested the impact of
almonds consumed as a snack within the context of a typical Korean diet on
cardiovascular risk factors. METHODS: We conducted a randomized, crossover trial
in a free-living setting with a 2-week run-in period, two 4-week intervention
phases, and a 2-week washout period between interventions. Eighty four
overweight/obese participants (11 M/73 F; 52.4 +/- 0.6 year; 25.4 +/- 0.22 kg/m2)
consumed either 56 g of almonds or isocaloric cookies daily for 4 weeks. RESULTS:
Mean % daily energy intake at baseline was 64.8, 21.3, and 14.9% from
carbohydrate, fat, and protein, respectively. The addition of 56 g of almonds
daily decreased carbohydrate energy to 55.0%, increased fat to 32.0%, and
maintained protein at 14.7%. Consuming the almonds increased intake of MUFA by
192.3%, PUFA by 84.5%, vitamin E by 102.7%, and dietary fiber by 11.8% and
decreased % energy from carbohydrate by 14.1%. Total caloric intake was increased
by the almonds, but body weight, waist circumference, and body composition were
not affected. Almonds in overweight and obese Korean adults decreased TC, LDL-C,
and non-HDL-C by 5.5, 4.6, and 6.4%, respectively, compared to the cookie control
(P <= 0.05). Almonds increased plasma alpha-tocopherol by 8.5% (P <= 0.05) from
the baseline and tended to increase its value as compared to cookies (P = 0.055).
Neither the almonds nor cookies altered plasma protein carbonyls, MDA or oxLDL.
Of serum inflammatory markers, IL-10 was decreased by almond intake (P <= 0.05),
and ICAM-1, IL-1beta, and IL-6 tended to be lower with almonds, compared to the
cookies. CONCLUSIONS: Almonds at 56 g/day consumed as a snack favorably modified
the Korean diet by increasing MUFA, PUFA, vitamin E, and dietary fiber intake and
decreasing % energy intake from carbohydrate. Almonds also enhanced plasma alpha
tocopherol status and serum TC and LDL-C in overweight and obese Koreans. Thus,
including almonds in typical Korean diets as a snack can help healthy
overweight/obese individuals improve nutritional status and reduce their risk for
CVD.
PMID- 28695325
TI - A modified response of NAFLD patients with non-significant fibrosis in
nutritional counseling according to GCKR rs1260326.
AB - AIM: To investigate the association between GCKR gene and nutritional treatment
in NAFLD-related biomarkers. METHODS: This was an open-label and single-arm
clinical trial in 44 overweight or obese adults with NAFLD receiving nutritional
counseling for 6 months. Nutritional data, MedDietScore, clinical, biochemical,
inflammatory and oxidative stress biomarkers were evaluated before and after
intervention. Further, we genotyped GCKR rs1260326 and in T-allele carriers and
non-Tau-carriers we assessed associations between the GCKR variant and
nutritional counseling related to change in all biomarkers evaluated. RESULTS:
Anthropometric measurements were significantly reduced after the end of the
intervention in patients assigned to nutritional counseling. Liver imaging and
fibrosis were significantly improved. GCKR rs1260326 T-allele frequency was
46.7%. T-carriers responded better to nutritional counseling regarding fasting
blood glucose levels (mean6-0 change = -4.94 mg/dL (+/-9.33), p = 0.005), whereas
non-T-carriers did not benefit from the intervention regarding glucose. On the
other hand, levels of oxLDL decreased in the non-T-carriers group after the
intervention, but not in T-carriers. CONCLUSIONS: Our results show that GCKR
rs1260326 T-allele is associated with better response of NAFLD patients to
nutritional treatment regarding fasting blood glucose, but not oxLDL levels.
Despite this important finding in the field of nutrigenetics, it is tricky to
generalize this effect unless larger studies are conducted.
PMID- 28695326
TI - Anti-melanogenic effect of gomisin N from Schisandra chinensis (Turcz.) Baillon
(Schisandraceae) in melanoma cells.
AB - Overproduction and accumulation of melanin in the skin can lead to pigmentation
disorders, such as freckles and melasma. Many researchers are studying the
regulation of melanogenesis in the skin with the aim of developing whitening
cosmetics. In this study, bioactivity-guided separation of the hexane fraction of
Schisandra chinensis (Turcz.) Baillon extract yielded five major compounds, beta
chamigrenal, alpha-ylangenol, gomisin N, gomisin A, and schisandrin. The
structures were identified by using 1H-NMR and 13C-NMR spectroscopy and comparing
the spectral data with published data. Melanogenesis inhibitory activity assay in
alpha-melanocyte-stimulating hormone (alpha-MSH)-induced B16F10 mouse melanoma
cells revealed that gomisin N was the active component and significantly
inhibited melanin synthesis in a concentration-dependent manner. Thus, we
evaluated the mechanism underlying its anti-melanogenic effect. Gomisin N
inhibited the expression of tyrosinase and microphthalmia-associated
transcription factor (MITF) in B16F10 cells, while it did not affect cAMP
response element binding protein (CREB) phosphorylation. Additionally, gomisin N
activated AKT phosphorylation, which inhibits MITF expression. Thus, our results
strongly suggest that the active compound, gomisin N, has potential for use in
cosmetics to reduce hyperpigmentation.
PMID- 28695327
TI - Aqueous Polymer Dispersion Coating Used for Osmotic Pump Tablets: Membrane
Property Investigation and IVIVC Evaluation.
AB - The objective of this study was to investigate the fundamental properties of
propranolol hydrochloride osmotic pump tablets coated by aqueous polymer
dispersion, simultaneously exploring the in vitro and in vivo correlation of the
tablet. The physicochemical properties and parameters of aqueous polymer
dispersion membranes (SEM, water uptake, and water vapor transmission
coefficient) were investigated. In addition, the release behavior and the in
vitro release and in vivo absorption profiles of the tablets coated by aqueous
polymer dispersion were investigated by comparing with propranolol hydrochloride
osmotic pump tablets coated by an organic solvent. Results showed that the
similarity factor (f 2) between cellulose acetate-coated tablet and Eudragit
coated tablet was 78.1, and f 2 between cellulose acetate-coated tablet and
Kollicoat-coated tablet was 77.6. The linear IVIVC of Eudragit-coated and
Kollicoat-coated osmotic pump tablets was determined, which confirmed excellent
correlation between the absorption in vivo and the drug release in vitro.
Consequently, the membrane coated by aqueous polymer dispersion or organic
solvent has similar in vitro release rates of controlled release. Also, compared
with organic solvent coating, aqueous polymer dispersion has numerous advantages,
such as reduced toxicity and no environmental damage. Therefore, the aqueous
polymer dispersion technology has enormous potential as a replacement of organic
solvent coating.
PMID- 28695328
TI - Study of the Emitted Dose After Two Separate Inhalations at Different Inhalation
Flow Rates and Volumes and an Assessment of Aerodynamic Characteristics of
Indacaterol Onbrez Breezhaler(r) 150 and 300 MUg.
AB - Onbrez Breezhaler(r) is a low-resistance capsule-based device that was developed
to deliver indacaterol maleate. The study was designed to investigate the effects
of both maximum flow rate (MIF) and inhalation volume (Vin) on the dose emission
of indacaterol 150 and 300 MUg dose strengths after one and two inhalations using
dose unit sampling apparatus (DUSA) as well as to study the aerodynamic
characteristics of indacaterol Breezhaler(r) using the Andersen cascade impactor
(ACI) at a different set of MIF and Vin. Indacaterol 150 and 300 MUg contain
equal amounts of lactose per carrier. However, 150 MUg has the smallest carrier
size. The particle size distribution (PSD) of indacaterol DPI formulations 150
and 300 MUg showed that the density of fine particles increased with the increase
of the primary pressure. For both strengths (150 MUg and 300 MUg), ED1 increased
and ED2 decreased when the inhalation flow rate and inhaled volume increased. The
reduction in ED1 and subsequent increase in ED2 was such that when the Vin is
greater than 1 L, then 60 L/min could be regarded as the minimum MIF. The
Breezhaler was effective in producing respirable particles with an MMAD <=5 MUm
irrespective of the inhalation flow rate, but the mass fraction of particles with
an aerodynamic diameter <3 MUm is more pronounced between 60 and 90 L/min. The
dose emission of indacaterol was comparable for both dose strengths 150 and 300
MUg. These in vitro results suggest that a minimum MIF of 60 L/min is required
during routine use of Onbrez Breezhaler(r), and confirm the good practice to make
two separate inhalations from the same dose.
PMID- 28695329
TI - Topically used herbal products for the treatment of hair loss: preclinical and
clinical studies.
AB - Currently available conventional therapies of hair loss using synthetic drugs are
still imperfect and have a number of limitations. Their effectiveness as well as
the safety of their use is often questioned. It has led to an increased interest
in alternative treatments with fewer side-effects such as formulations containing
herbs and/or their active constituents. For this purpose several electronic
databases and hand-searched references were used to summarize current knowledge
regarding topically used herbal products for the treatment of hair loss acquired
on the basis of preclinical and clinical studies. Moreover, mechanism of their
action, follicular penetration and possible adverse effect of herbal products
will be also described.
PMID- 28695330
TI - The metabolic analysis of psoriasis identifies the associated metabolites while
providing computational models for the monitoring of the disease.
AB - The majority of studies on psoriasis have focused on explaining the genetic
background and its associations with the immune system's response. The aim of
this study was to identify the low-molecular weight compounds contributing to the
metabolomic profile of psoriasis and to provide computational models that help
with the classification and monitoring of the severity of the disease. We
compared the results from targeted and untargeted analyses of patients' serums
with plaque psoriasis to controls. The main differences were found in the
concentrations of acylcarnitines, phosphatidylcholines, amino acids, urea,
phytol, and 1,11-undecanedicarboxylic acid. The data from the targeted analysis
were used to build classification models for psoriasis. The results from this
study provide an overview of the metabolomic serum profile of psoriasis along
with promising statistical models for the monitoring of the disease.
PMID- 28695331
TI - Vorinostat and Mithramycin A in combination therapy as an interesting strategy
for the treatment of Sezary T lymphoma: a transcriptomic approach.
AB - SAHA (vorinostat) is a histone deacetylase inhibitor approved by the USA Food and
Drug Administration (FDA) for treating advanced refractory cutaneous T cell
lymphomas. As SAHA alters the expression of many genes under control of the Sp1
transcription factor, we examined the effect of its association with the FDA
approved anticancer antibiotic Mithramycin A (MTR, plicamycin), a competitive
inhibitor of Sp1 binding to DNA. Sezary syndrome (SS) cells, expanded ex vivo
from peripheral blood mononuclear cells of 4 patients, were tested for their
sensitivity to the drugs regarding cytotoxicity and differential responsive gene
expression. Multivariate statistical methods were used to identify genes whose
expression is altered by SAHA, MTR, and the synergist effect of the two drugs.
MTR, like SAHA, induced the apoptosis of SS cells, while the two drugs in
combination showed clear synergy or potentiation. Expression data stressed a
likely important role of additive or synergistic epigenetic modifications in the
combined effect of the two drugs, while direct inhibition of Sp1-dependent
transcription seemed to have only limited impact. Ontological analysis of
modified gene expression suggested that the two drugs, either independently or
synergistically, counteracted many intertwined pro-survival pathways deregulated
in SS cells, resistance of these tumors to intrinsic and extrinsic apoptosis,
abnormal adhesion migration, and invasive properties, as well as
immunosuppressive behavior. Our findings provide preliminary clues on the
individual and combined effects of SAHA and MTR in SS cells and highlight a
potential therapeutic interest of this novel pair of drugs for treatment of SS
patients.
PMID- 28695332
TI - Systematic identification and characterization of stress-inducible heat shock
proteins (HSPs) in the salmon louse (Lepeophtheirus salmonis).
AB - Salmon lice (Lepeophtheirus salmonis) are parasitic copepods, living mainly on
Atlantic salmon and leading to large economical losses in aquaculture every year.
Due to the emergence of resistances to several drugs, alternative treatments are
developed, including treatment with hydrogen peroxide, freshwater or thermal
treatment. The present study gives a first overview of the thermotolerance and
stress response of salmon lice. Sea lice nauplii acclimated to 10 degrees C can
survive heat shocks up to 30 degrees C and are capable of hardening by a
sublethal heat shock. We searched in the genome for heat shock protein (HSP)
encoding genes and tested their inducibility after heat shock, changes in
salinity and treatment with hydrogen peroxide, employing microfluidic qPCRs. We
assessed 38 candidate genes, belonging to the small HSP, HSP40, HSP70 and HSP90
families. Nine of these genes showed strong induction after a non-lethal heat
shock. In contrast, only three and two of these genes were induced after changes
in salinity and incubation in hydrogen peroxide, respectively. This work provides
the basis for further work on the stress response on the economically important
parasite L. salmonis.
PMID- 28695333
TI - The initial analysis of a serine proteinase gene (AccSp10) from Apis cerana
cerana: possible involvement in pupal development, innate immunity and abiotic
stress responses.
AB - Serine proteinases play important roles in innate immunity and insect
development. We isolated a serine proteinase gene, designated AccSp10, from the
Chinese honeybees (Apis cerana cerana). RT-qPCR and a Western blot analysis at
different pupal development stages indicated that AccSp10 might be involved in
melanin formation in pupae and promote pupal development. In adult workers, the
expression of AccSp10 was upregulated by treatments mimicking harmful
environments such as the presence of Bacillus bombysepticus, different
temperatures (4, 24 and 42 degrees C), HgCl2, H2O2 and paraquat; the exception
was treatment with VC (vitamin C), which did not upregulate AccSp10 expression.
Western blot confirmed the results. A disc diffusion assay indicated that
recombinant AccSp10 accelerated E. coli cell death during stimulation with
harmful substances (HgCl2, paraquat and cumene hydroperoxide). These findings
suggest that AccSp10 may be involved in the pupal development of Chinese
honeybees and protection against microorganisms and abiotic harms.
PMID- 28695334
TI - Arbuscular mycorrhizas are present on Spitsbergen.
AB - A previous study of 76 plant species on Spitsbergen in the High Arctic concluded
that structures resembling arbuscular mycorrhizas were absent from roots. Here,
we report a survey examining the roots of 13 grass and forb species collected
from 12 sites on the island for arbuscular mycorrhizal (AM) colonisation. Of the
102 individuals collected, we recorded AM endophytes in the roots of 41 plants of
11 species (Alopecurus ovatus, Deschampsia alpina, Festuca rubra ssp.
richardsonii, putative viviparous hybrids of Poa arctica and Poa pratensis, Poa
arctica ssp. arctica, Trisetum spicatum, Coptidium spitsbergense, Ranunculus
nivalis, Ranunculus pygmaeus, Ranunculus sulphureus and Taraxacum arcticum)
sampled from 10 sites. Both coarse AM endophyte, with hyphae of 5-10 MUm width,
vesicles and occasional arbuscules, and fine endophyte, consisting of hyphae of 1
3 MUm width and sparse arbuscules, were recorded in roots. Coarse AM hyphae,
vesicles, arbuscules and fine endophyte hyphae occupied 1.0-30.7, 0.8-18.3, 0.7
11.9 and 0.7-12.8% of the root lengths of colonised plants, respectively.
Principal component analysis indicated no associations between the abundances of
AM structures in roots and edaphic factors. We conclude that the AM symbiosis is
present in grass and forb roots on Spitsbergen.
PMID- 28695335
TI - Glutamatergic system and mTOR-signaling pathway participate in the antidepressant
like effect of inosine in the tail suspension test.
AB - Glutamatergic system and mTOR signaling pathway have been proposed to be
important targets for pharmacological treatment of major depressive disorder.
Previous studies have shown that inosine, an endogenous purine, is able to exert
a remarkable antidepressant-like effect in mice. Nevertheless, the role of
glutamatergic system and mTOR in this effect was not previously determined. This
study was designed to investigate the possible modulation of NMDA receptors
(NMDAR), AMPA receptors (AMPAR) and mTOR complex 1 (mTORC1) signaling pathway in
the inosine anti-immobility effect in the tail suspension test (TST) in mice. Pre
treatment of mice with NMDA (0.1 pmol/mouse, NMDAR agonist, i.c.v.) and D-serine
(30 MUg/mouse, NMDAR co-agonist, i.c.v.) prevented inosine (10 mg/kg, i.p.) anti
immobility effect in the TST. In addition, a synergistic antidepressant-like
effect was observed when a sub-effective dose of inosine (0.1 mg/kg, i.p.) was
combined with sub-effective doses of NMDAR antagonists MK-801 (0.001 mg/kg, p.o.)
or ketamine (0.1 mg/kg, i.p.). Conversely, the antidepressant-like effect
elicited by inosine was not altered by pre-treatment with AMPAR antagonist, DNQX
(2.5 MUg/mouse, i.c.v.). The mTORC1 inhibitor rapamycin (0.2 nmol/mouse, i.c.v.)
prevented the inosine anti-immobility effect in the TST. Noteworthy, inosine
treatment did not change the immunocontent of the synaptic proteins PSD95, GluA1
and synapsin I. Mice locomotor activity assessed by open-field test, was not
altered by treatments. Taken together, this study shows a pivotal role of NMDAR
inhibition and mTORC1 activation for inosine antidepressant-like effect and
extends the knowledge concerning the molecular mechanism and potential of inosine
for antidepressant strategies.
PMID- 28695336
TI - Experimentally induced intrauterine growth restriction in rabbits leads to
differential remodelling of left versus right ventricular myocardial
microstructure.
AB - Intrauterine growth restriction (IUGR) is associated with foetal cardiac
remodelling and dysfunction together with increased risk of cardiovascular
disease in adulthood. Experimental data concerning effects of IUGR on
cardiomyocyte and microvascularization anatomy are inconsistent and it is unknown
whether both ventricles are similarly susceptible to in utero undersupply. Foetal
IUGR was induced in pregnant rabbits at 25 days of gestation by selective
ligation of uteroplacental vessels. Foetal echocardiography showed systolic and
diastolic dysfunction of both ventricles and body and heart weight were
significantly reduced in response to IUGR. Design-based stereology revealed a
decrease in cardiomyocyte number in both ventricles which was only in the left
ventricle accompanied by a significantly higher cardiomyocyte mean volume. The
proportion of mono- and bi-nucleated cardiomyocytes was unaltered between the
groups indicating a similar maturation status. The number and length of cardiac
capillaries in IUGR offspring was diminished in left but not in right ventricles.
Foetal left and right ventricles are differently affected by placental
insufficiency. While cardiomyocyte numbers are diminished in both ventricles,
hypertrophic remodelling of cardiomyocytes and alterations in
microvascularization is rather a left ventricular adaptation to IUGR. These
unequal structural changes may be related to loading and developmental
differences of the left and right ventricles.
PMID- 28695337
TI - Development of pediatric neurosurgical service at Dr. Soetomo Hospital, Surabaya,
Indonesia.
AB - PURPOSE: This review traces the history of pediatric neurosurgery at Dr. Soetomo
General Hospital (DSGH) and its role in advancing the field of pediatric
neurosurgery. METHODS: The history, the founding fathers, and the next
generations of the pediatric neurosurgery in DSGH were traced back from original
sources and authors' life stories. RESULT: Pediatric neurosurgical service at
DSGH has its own unique perspective being a pediatric service in general hospital
setting. It serves second largest city of Indonesia - the fifth most populated
country in the world. Historical vignette and future perspectives are narratively
presented. CONCLUSION: As a pediatric neurosurgical service at general hospital
in developing country, its development deserves a special mention.
PMID- 28695338
TI - Management of concomitant scoliosis and tethered cord syndrome in non-spina
bifida pediatric population.
AB - BACKGROUND: The management of concomitant scoliosis and tethered cord syndrome in
the non-spina bifida pediatric population is challenging. In the present study,
we evaluate the efficacy of different treatment modalities and propose a
treatment plan for the management of affected patients. METHODS: A systematic
literature review was conducted by querying the MEDLINE, PubMed, Cochrane,
EMBASE, Scopus, and Web of Science databases for papers published between January
1996 and June 2016 and reporting on concomitant scoliosis and tethered cord. We
excluded animal studies, non-English papers as well as papers reporting on
patients with multiple concomitant intraspinal anomalies such as spina bifida.
RESULTS: Out of 1993 articles, only 13 met our inclusion criteria. These 13
articles described six main management approaches: Observation, cord untethering
only, cord untethering followed by deformity correction, simultaneous cord
untethering and deformity correction, and deformity correction without
untethering. Selection of the best approach is a function of the patient's
symptomatology and Cobb angle. CONCLUSION: We propose treatment plan for the
management of patients with concomitant tethered cord syndrome and spinal
deformity. Asymptomatic patients can be followed conservatively and managed as
scoliosis patients with no need for untethering. Surgical management in a staged
fashion seems appropriate in symptomatic patients with a Cobb angle less than 35
degrees . In these patients, deformity can improve following untethering, thus
sparing the patient the risks of surgical correction of scoliosis. Staged or non
staged cord untethering and curve correction seem to be adequate in symptomatic
patients with Cobb angle >35 degrees as these patients are likely to require
both untethering and deformity correction.
PMID- 28695339
TI - Different information by MRI compare to ultrasound in fetal intracranial space
occupying lesions.
AB - PURPOSE: The purpose of this study was to evaluate the value of prenatal magnetic
resonance imaging (MRI) in characterizing fetal intracranial space occupying
lesions in comparison to prenatal ultrasound. METHODS: This retrospective study
included 50 fetuses (mean age 26 years, mean gestational weeks 31 + 1 GW) with
intracranial space occupying lesions, suspected by prenatal screening ultrasound.
T2-weighted, T1-weighted, SSFP, and diffusion-weighted sequences of the fetal
brain were obtained on a 1.5 T unit. Pathology (n = 5), postmortem MRI (n = 3),
or postnatal US (n = 42) was available as standard of reference. RESULTS: The
fetal MRI provided correct diagnosis in 49 cases (98%), while 35 (70%) by
ultrasound, and MRI failed in 1 case (2%), while ultrasound failed in 15 cases
(30%). Fetal MR and ultrasound were concordant in 35 of 50 cases (70%),
completely discordant in 4 (8%), and partially discordant in 11 (22%) cases.
CONCLUSIONS: MRI could provide detailed information about the minor lesions, such
as focal hemorrhage and periventricular nodules. Meanwhile, it could provide
whole view of the lesion in order to delineate the surrounding anatomical
structure. But there are still some limitations of its soft-tissue resolution in
a case with teratoma; more effort is needed to improve the sequences.
PMID- 28695340
TI - Tropomyosin receptor kinase C (TrkC) expression in medulloblastoma: relation to
the molecular subgroups and impact on treatment response.
AB - PURPOSE: High messenger RNA (mRNA) expression of the tropomyosin receptor kinase
C gene (TrkC) has been associated with favorable survival in medulloblastoma
patients. Untested is whether it plays a role through modulating the response to
therapy or whether it might be a surrogate marker for a favorable molecular
subgroup. METHODS: The medulloblastoma-derived cell line DAOY was stably
transfected to overexpress TrkC (clone DAOY-TrkC) and compared to a control
(clone DAOY-EV, empty vector transfected). Cell viability (MTS assay) was tested
after irradiation or incubation with chemotherapeutic drugs. Neuroradiologic
response to postoperative chemotherapy or craniospinal irradiation (CSI) of
medulloblastoma patients aged 3-21 years with postoperative residual disease
treated within the consecutive trials HIT'91/HIT2000 was compared to TrkC mRNA
expression in their tumor samples. Five well-characterized independent expression
profiling studies covering together 686 medulloblastoma patients were analyzed
for TrkC levels according to the molecular subgroups. RESULTS: Cell viability of
DAOY-TrkC compared to DAOY-EV was not different after exposure to increasing
doses of irradiation, cisplatin, etoposide, or vincristine. While TrkC mRNA
expression tended to be higher in non-responders (n = 5/19) to postoperative CSI
(p = 0.03, ratio 15.5, 95% CI 9-267), this was the case in responders (n = 23/43)
to chemotherapy (p = 0.04, ratio 6.1, 95% CI 1.1-35), both analyzed with Mann
Whitney U test (not significant after Bonferroni adjustment). The highest TrkC
mRNA levels were found in the SHH subgroup across all expression-profiling
studies. CONCLUSIONS: High TrkC mRNA expression appears to be frequent in the SHH
subgroup and seems not to have a major effect on therapy responsiveness in
medulloblastoma patients.
PMID- 28695341
TI - Fetal ventriculomegaly: diagnostic, ethical and semantic considerations.
PMID- 28695342
TI - Thyroid Nodule Classification in Ultrasound Images by Fine-Tuning Deep
Convolutional Neural Network.
AB - With many thyroid nodules being incidentally detected, it is important to
identify as many malignant nodules as possible while excluding those that are
highly likely to be benign from fine needle aspiration (FNA) biopsies or
surgeries. This paper presents a computer-aided diagnosis (CAD) system for
classifying thyroid nodules in ultrasound images. We use deep learning approach
to extract features from thyroid ultrasound images. Ultrasound images are pre
processed to calibrate their scale and remove the artifacts. A pre-trained
GoogLeNet model is then fine-tuned using the pre-processed image samples which
leads to superior feature extraction. The extracted features of the thyroid
ultrasound images are sent to a Cost-sensitive Random Forest classifier to
classify the images into "malignant" and "benign" cases. The experimental results
show the proposed fine-tuned GoogLeNet model achieves excellent classification
performance, attaining 98.29% classification accuracy, 99.10% sensitivity and
93.90% specificity for the images in an open access database (Pedraza et al. 16),
while 96.34% classification accuracy, 86% sensitivity and 99% specificity for the
images in our local health region database.
PMID- 28695343
TI - Posterior colporrhaphy does not affect the urethral closure mechanism.
AB - INTRODUCTION AND HYPOTHESIS: Studies have suggested that a posterior vaginal wall
prolapse might compress the urethra and mask stress urinary incontinence (SUI),
much like an anterior vaginal wall prolapse. A recent study with urethral
pressure reflectometry (UPR) has shown that the urethral closure mechanism
deteriorates after anterior colporrhaphy; this could explain the occurrence of
postoperative de novo SUI. We hypothesized that urethral pressure would also
decrease after posterior colporrhaphy. METHODS: This was a prospective,
observational study where women with posterior vaginal wall prolapse >=stage II
were examined before and after posterior colporrhaphy. We performed prolapse
staging according to the Pelvic Organ Prolapse Quantification system, UPR
measurements at rest, during squeezing and straining, and standardized stress
tests with 300 ml saline. The women filled out International Consultation on
Incontinence-Urinary incontinence (ICIQ-UI) short forms. The sample size was 18,
with a power of 99.9% and a level of significance of 5%. Parameters were compared
using paired t tests or Fisher's exact test, where appropriate; p values <0.05
were considered statistically significant. RESULTS: Eighteen women with posterior
vaginal wall prolapse >=stage II were recruited. One woman did not undergo
surgery. There were no changes in urethral pressure at rest (p = 0.4), during
squeezing (p = 0.2) or straining (p = 0.2), before and after surgery. The results
of the stress tests and ICIQ-UI short forms were the same after surgery.
CONCLUSIONS: The urethral closure mechanism is not affected by posterior
colporrhaphy. Our study does not support the theory that the posterior vaginal
wall prolapse compresses the urethra and masks SUI.
PMID- 28695344
TI - Genital tract fistula: a case series from a tertiary centre in South Africa.
AB - INTRODUCTION AND HYPOTHESIS: We describe the demographic profile, aetiology,
management and surgical outcomes in women with genital tract fistula presenting
to a tertiary urogynaecology unit. METHODS: This retrospective audit included 87
patients managed in our unit between 2008 and 2015. Frequencies and means with
standard deviations are presented for categorical and continuous data. Continuous
dependent variables are categorized as above or below the median for bivariate
analyses performed using the chi-squared test (alpha = 0.05). RESULTS: The mean
age of the women was 34.7 years, 64.4% were Black African, 70.2% were
multiparous, 49.4% were married, 82.8% were employed, and 21.8% were HIV
infected, with 47.4% on antiretroviral treatment. Vesicovaginal (47.1%) and
rectovaginal (41.4%) fistula were the most frequent injuries. The majority of the
injuries (67.8%) were obstetric, with 26.4% occurring during caesarean delivery.
Repair had been attempted previously in 43.7% of patients. In 63.2% of the
repairs the approach was vaginal and in 35.6% abdominal. Interposition grafts
were used in 23% of repairs. In 85.1% of patients the initial repair at our
centre was successful. Patients with multiple repairs were more likely to have
complications (p = 0.03). HIV infection was not significantly associated with
complications. CONCLUSIONS: A high rate of successful repair was found, with
previous unsuccessful repairs associated with poorer outcomes, highlighting the
need for centralized management.
PMID- 28695345
TI - Is pain relief after vaginal mesh and/or sling removal durable long term?
AB - INTRODUCTION AND HYPOTHESIS: This study was to review our experience of pain
relief durability in women who experienced initial pain resolution after vaginal
mesh and/or sling removal (VMSR). METHODS: A retrospective chart review of
consecutive, nonneurogenic women who underwent VMSR for pain and reported
persistent pain relief at the 6-month postoperative follow-up visit were
assessed. Pre- and postoperative data collected were self-reported chief
complaints, physical examination, other medical conditions associated with
chronic pain, use of pain medications, Urogenital Distress Inventory-6 (in which
question 6 specifically addresses pain), and the Numerical Pain Rating Scale
(NPRS). Success was defined by continued resolution of pain assessed by score of
0 on NPRS (0 none to 10 terrible), (0-1 on the Urogenital Distress Inventory-6
(UDI-6) question 6, subjective report of pain-free status, and/or no chronic use
of pain medications other than those prescribed for non-mesh-related pain.
RESULTS: Between 2006 and 2015, 125 of 356 women met study criteria. Mean follow
up after VMSR was 3.5 (range 0.5-10) years. Among 25 women who did not meet
success criteria by questionnaire answers or subjective report, 21 had causes
unrelated to their original mesh/sling placement and were pain free after they
were addressed. Four women experienced delayed mesh-related pain return at 28,
46, 47, and 54 months, respectively; two required mesh removal surgery.
Involvement in lawsuits and chronic pain-related medical conditions did not
affect the durability of pain relief. CONCLUSIONS: At a mean follow-up of 3.5
years, the original pain relief noted after VMSR was durably maintained.
PMID- 28695347
TI - Telavancin in the Treatment of Concurrent Staphylococcus aureus Bacteremia: A
Retrospective Analysis of ATLAS and ATTAIN Studies.
AB - INTRODUCTION: Concurrent Staphylococcus aureus bacteremia (SAB) worsens outcomes
and increases mortality in patients with complicated skin and skin structure
infections (cSSSI), hospital-acquired bacterial pneumonia, and ventilator
associated bacterial pneumonia (HABP/VABP). These challenges highlight the need
for alternative treatments. Telavancin (TLV), a bactericidal lipoglycopeptide
with high in vitro potency, effectively treats patients with cSSSI and HABP/VABP
caused by Gram-positive pathogens, particularly S. aureus. METHODS: This
retrospective analysis evaluated patients from the Assessment of Telavancin in
Complicated Skin and Skin Structure Infections and Assessment of Telavancin for
Treatment of Hospital-Acquired Pneumonia studies with baseline, concurrent SAB.
Differences in the clinical cure rates at test-of-cure and safety outcomes were
compared for TLV vs vancomycin (VAN) treatment groups. RESULTS: A total of 105
patients, 32 cSSSI and 73 HABP/VABP, had baseline, concurrent SAB. The clinical
cure rates for all-treated SAB patients in the cSSSI (TLV 57.1% and VAN 54.5%)
and HABP/VABP (TLV 54.3% and VAN 47.2%) groups were comparable. For both types of
infections, the safety profile of TLV and VAN showed similar incidences of
adverse events (AEs), serious AEs, or AEs leading to discontinuation. One VAN
treated patient died in the cSSSI group, and there were 13 deaths in each
treatment arm of the HABP/VABP group. CONCLUSION: This retrospective analysis
demonstrated that TLV is clinically comparable in both efficacy and safety to
VAN, and, therefore, may be an appropriate therapeutic option for the treatment
of patients with HABP/VABP or cSSSI and concurrent SAB. Given the limited sample
size in this subgroup, the interpretation of these results is limited. FUNDING:
Theravance Biopharma Antibiotics, Inc.
PMID- 28695348
TI - Acquisition of joint attention by olive baboons gesturing toward humans.
AB - Joint attention is a core ability of human social cognition which broadly refers
to the coordination of attention with both the presence and activity of social
partners. In both human and non-human primates, joint attention can be assessed
from behaviour; gestures and gaze alternation between the partner and a distal
object are standard behavioural manifestations of joint attention. Here we
examined the acquisition of joint attention in olive baboons as a function of
their individual experience of a human partner's attentional states during
training regimes. Eleven olive baboons (Papio anubis) were observed during their
training to perform food-requesting gestures, which occurred either by (1) a
human facing them (face condition), or (2) by a human positioned in profile who
never turned to them (profile condition). We found neither gestures nor gaze
alternation were present at the start of the training but rather developed over
the training period. Only baboons in the face condition showed an increase in the
number of gaze alternations, and their gaze pattern progressively shifted to a
coordinated sequence in which gazes and gestures were coordinated in time. In
contrast, baboons trained by a human in profile showed significantly less
coordination of gazes with gestures but still learned to request food with their
gestures. These results suggest that the partner's social attention plays an
important role in the acquisition of visual joint attention and, to a lesser
extent, in gesture learning in baboons. Interspecific interactions appear to
offer rich opportunities to manipulate and thus identify the social contexts in
which socio-communicative skills develop.
PMID- 28695349
TI - Temperament and problem solving in a population of adolescent guide dogs.
AB - It is often assumed that measures of temperament within individuals are more
correlated to one another than to measures of problem solving. However, the exact
relationship between temperament and problem-solving tasks remains unclear
because large-scale studies have typically focused on each independently. To
explore this relationship, we tested 119 prospective adolescent guide dogs on a
battery of 11 temperament and problem-solving tasks. We then summarized the data
using both confirmatory factor analysis and exploratory principal components
analysis. Results of confirmatory analysis revealed that a priori separation of
tests as measuring either temperament or problem solving led to weak results,
poor model fit, some construct validity, and no predictive validity. In contrast,
results of exploratory analysis were best summarized by principal components that
mixed temperament and problem-solving traits. These components had both construct
and predictive validity (i.e., association with success in the guide dog training
program). We conclude that there is complex interplay between tasks of
"temperament" and "problem solving" and that the study of both together will be
more informative than approaches that consider either in isolation.
PMID- 28695350
TI - Early markers of lexical stress in visual word recognition.
AB - The goal of the present study was to investigate the time-course of
suprasegmental information in visual word recognition. To this aim we measured
event-related brain potentials (ERPs) during a simple lexical decision task in
Italian. Two factors were manipulated: Stress dominance (the most frequent stress
type) and stress neighborhood consistency (the proportion and number of existent
words sharing orthographic ending and stress pattern). Participants were
presented with target words either bearing dominant (on the penultimate syllable;
'graNIta,' 'seNIle,' slush, senile) or non-dominant stress (on the
antepenultimate syllable; 'MISsile,' 'BIbita,' missile, drink), and either having
a consistent (graNIta, MISsile) or an inconsistent stress neighborhood (seNIle,
BIbita). Our results showed in the initial stages of processing an effect that we
interpreted as an early orthographic marker of stress neighborhood in interaction
with dominance. Later, from 250 ms after target onset, a marker of the lexical
stress difference also emerged. The role of stress assignment in word recognition
is discussed.
PMID- 28695351
TI - Robustness and Effectiveness of the Triage System in the Pediatric Context.
AB - BACKGROUND: The increasing use of emergency departments (EDs) potentially
compromises their effectiveness and quality. The evaluation of the performance of
the triage code system in a pediatric context is important because waiting time
affects the quality of care for acutely ill patients. OBJECTIVE: In this study,
we aimed to assess the effectiveness and robustness of the triage code system in
a pediatric context and identify the determinants of waiting times for urgent and
non-urgent patients. METHODS: Data regarding 37,767 pediatric patients who
accessed the ED of a major Italian pediatric hospital in 2015 were investigated
in order to study patient numbers and waiting times. The determinants of waiting
times for urgent and non-urgent patients, as well as variables referring to the
"supply side," such as periods of staff shortage, were analyzed using a survival
analysis framework. RESULTS: For urgent patients, the waiting time between triage
and the first physician assessment is generally below the standard threshold of
15 min and this is not affected by the number of non-urgent patients waiting for
care. Conversely, the waiting time for non-urgent patients is affected by ED
flow, periods of staff shortage, and non-clinical variables (age and
nationality). CONCLUSION: Our results suggest that the triage level assignation
system is effective in terms of safety for urgent patients. The current ED
organization adequately fulfills its primary goal of providing healthcare for
acutely ill patients.
PMID- 28695352
TI - Longitudinal Associations Between Childhood Obesity and Academic Achievement:
Systematic Review with Focus Group Data.
AB - PURPOSE: The purposes of this study were to review the evidence on longitudinal
associations between child and adolescent obesity and academic achievement and to
provide perceptions of adolescents with obesity and their parents on this topic.
RECENT FINDINGS: Synthesis of 31 studies (from 17 cohorts) suggested that
relationships between obesity and academic achievement are not well established,
except for adolescent girls' maths attainment, potentially mediated by both
weight-related bullying and executive cognitive functions. Focus groups with
adolescent girls with obesity confirmed experiences of psychosocial distress at
school particularly during Physical Education. Adolescents perceived that obesity
was not related to academic achievement directly, but by their attitude to
school. Interventions are warranted to promote psychosocial wellbeing and
cognitive abilities linked to academic achievement in adolescent girls with
obesity. Physical Education should be a positive experience for children and
adolescents with obesity.
PMID- 28695353
TI - Cardioprotection by the transfer of coronary effluent from ischaemic
preconditioned rat hearts: identification of cardioprotective humoral factors.
AB - Ischaemic preconditioning (IPC) provides myocardial resistance to
ischaemia/reperfusion (I/R) injuries. The protection afforded by IPC is not
limited to the target tissue but extends to remote tissues, suggesting a
mechanism mediated by humoral factors. The aim of the present study was to
identify the humoral factors that are responsible for the cardioprotection
induced by the coronary effluent transferred from IPC to naive hearts. Isolated
rat hearts were submitted to IPC (three cycles of 5 min I/R) before 30-min global
ischaemia and 60-min reperfusion. The coronary effluent (Efl_IPC) collected
during IPC was fractionated by ultrafiltration in different molecular weight
ranges (<3, 3-5, 5-10, 10-30, 30-50, and >50 kDa) and evaluated for
cardioprotective effects by perfusion before I/R in naive hearts. Only the <3, 5
10 and <10 kDa fractions of hydrophobic eluate reduced I/R injuries. The
cardioprotective effect of the 5-10 fraction was blocked by KATP channel blockers
and a PKC inhibitor. An Efl_IPC proteomic analysis revealed 14 cytoprotection
related proteins in 4-12 kDa peptides. HSP10 perfusion protected the heart
against I/R injuries. These data provide insights into the mechanisms of
cardioprotection in humoral factors released by IPC. Cardioprotection is afforded
by hydrophobic peptides in the 4-12 kDa size range, which activate pathways that
are dependent on PKC and KATP. Fourteen 4-12 kDa peptides were identified,
suggesting a potential therapeutic role for these molecules in ischaemic
diseases. One of these, HSP10, identified by mass spectrometry, reduced I/R
injuries and may be a potential candidate as a therapeutic target.
PMID- 28695354
TI - Mobile health clinic for the medical management of clinical sequelae experienced
by survivors of the 2013-2016 Ebola virus disease outbreak in Sierra Leone, West
Africa.
AB - An Ebola survivor Mobile Health Clinic (MHC) was established to implement lasting
changes in communities it operates by providing effective and efficient mobile
healthcare. After months of development, the MHC solution was operationalised in
February 2015, aiming to provide integrated primary healthcare services to
address the medical and psychosocial needs of Ebola virus (EBOV) survivors living
in areas with low medical coverage. A total of 910 medical consultations for 246
EBOV survivors were performed between 7 February 2015 and 10 June 2016. Females
constituted 148 (60.2%) whereas 6 (2.44%) were children under 5 years of age. The
most common complication was arthralgia 185 (75.2%), headache 98 (39.8%),
abdominal pain 167 (68%), myalgia 182 (73.6%), and skin disease 25 (10%).
Moreover, ocular problems were diagnosed in 84 survivors (34.1%), and 60 (24.4%)
suffered from psycho-trauma. Some 16 female survivors (10.8%) had miscarriages,
whereas 9 (6.1%) had complaints of oligomenorrhea, 7 (4.7%) loss of sexual desire
and 4 (2.7%) premature menopause. Five male survivors (5.1%) reported erectile
dysfunction and 10 (10.2%) loss of sexual desire. At least 221 (89.8%) reported
more than one complication. Other infectious diseases were common and no
clinically relevant differences were established from haematology and clinical
biochemistry laboratory results. Ibuprofen, paracetamol, anti-malaria drugs and
antibiotics were the most common medicines prescribed. Community participation is
critical for implantation of MHC among EBOV survivors. Future strategies for the
mobile clinics should include enrolment of survivors at discharge from treatment
centres with close monitoring follow-up activities, to address sequelae as they
arise, to reduce the potential for development of long-term disabilities.
PMID- 28695355
TI - Suggested new breakpoints of anti-MERS-CoV antibody ELISA titers: performance
analysis of serologic tests.
AB - To provide optimal cut-off values of anti-Middle East respiratory syndrome
coronavirus (MERS-CoV) serologic tests, we evaluated performance of ELISA IgG,
ELISA IgA, IFA IgM, and IFA IgG using 138 serum samples of 49 MERS-CoV-infected
patients and 219 serum samples of 219 rRT-PCR-negative MERS-CoV-exposed
healthcare personnel and patients. The performance analysis was conducted for two
different purposes: (1) prediction of neutralization activity in MERS-CoV
infected patients, and (2) epidemiologic surveillance of MERS-CoV infections
among MERS-CoV-exposed individuals. To evaluate performance according to serum
collection time, we used 'days post onset of illness (dpoi)' and 'days post
exposure (dpex)' assessing neutralization activity and infection diagnosis,
respectively. Performance of serologic tests improved with delayed sampling time,
being maximized after a seroconversion period. In predicting neutralization
activity, ELISA IgG tests showed optimal performance using sera collected after
21 dpoi at cut-off values of OD ratio 0.4 (sensitivity 100% and specificity
100%), and ELISA IgA showed optimal performance using sera collected after 14
dpoi at cut-off value of OD ratio 0.2 (sensitivity 85.2% and specificity 100%).
In diagnosis of MERS-CoV infection, ELISA IgG exhibited optimal performance using
sera collected after 28 dpex, at a cut-off value of OD ratio 0.2 (sensitivity
97.3% and specificity 92.9%). These new breakpoints are markedly lower than
previously suggested values (ELISA IgG OD ratio 1.1, sensitivity 34.8% and
specificity 100% in the present data set), and the performance data help
serologic tests to be practically used in the field of MERS management.
PMID- 28695356
TI - What are the differentiating clinical and MRI-features of enchondromas from low
grade chondrosarcomas?
AB - OBJECTIVES: To evaluate the role of clinical assessment, conventional and dynamic
contrast-enhanced MRI in differentiating enchondromas from chondrosarcomas of
long bone. METHODS: The following clinical and MRI findings were assessed: age,
gender, pain, pain attributable to lesion, tumour location, tumour length,
presence, depth of endosteal scalloping, bone marrow oedema, soft tissue oedema,
cortical destruction, periosteal reaction, bone expansion, macroscopic fat,
calcification, soft tissue mass, haemorrhage, dynamic contrast-enhanced MRI.
Clinical and MRI findings were compared with histopathological grading. RESULTS:
Sixty patients with central chondroid tumours were included (27 enchondromas, 10
cartilaginous lesions of unknown malignant potential, 15 grade 1 chondrosarcomas,
8 high-grade chondrosarcomas). Pain attributed to lesion, tumour length,
endosteal scalloping > 2/3, cortical destruction, bone expansion and soft tissue
mass were differentiating features between enchondromas and grade 1
chondrosarcomas. Dynamic contrast-enhanced MRI could not differentiate
enchondromas from grade 1 chondrosarcomas. CONCLUSIONS: Previously reported
imaging signs of chondrosarcomas are useful in the diagnosis of grade 1 lesions
but have lower sensitivity than in higher grade lesions. Deep endosteal
scalloping is the most sensitive imaging sign of grade 1 chondrosarcomas. Pain
due to the lesion is an important clinical sign of grade 1 chondrosarcomas.
Dynamic contrast-enhanced MRI is not useful in differentiating enchondromas from
grade 1 chondrosarcomas. KEY POINTS: * Differentiation of enchondroma from low
grade chondrosarcoma is challenging for radiologists and pathologists. * The
utility of clinical assessment, conventional and dynamic contrast-enhanced MRI
was uncertain. * Clinical assessment and conventional MRI aid in differentiating
enchondromas from low-grade chondrosarcoma. * Dynamic contrast-enhanced MRI
cannot differentiate enchondromas from grade 1 chondrosarcoma.
PMID- 28695357
TI - Primary lower limb lymphoedema: classification with non-contrast MR lymphography.
AB - PURPOSE: The purpose of the present study was to analyse the performance of non
contrast MR lymphography for the classification of primary lower limb lymphoedema
in 121 consecutive patients with 187 primary lower limb lymphoedemas. MATERIALS
AND METHODS: 121 consecutive patients with clinically diagnosed primary lower
limb lymphoedema underwent non-contrast MR lymphography with a free-breathing 3D
fast spin-echo sequence with a very long TR/TE (4000/884 ms). MR examinations
were retrospectively reviewed for severity of lymphoedema (absent, mild,
moderate, severe) and characteristics of inguinal lymph nodes and iliac and
inguinal lymphatic trunks graded as aplasic (no lymph nodes or lymphatic trunks),
hypoplasic (less lymph nodes or lymphatic trunks), normal and hyperplasic (more
lymph nodes or more and/or dilated trunks). RESULTS: There was an excellent
correlation between clinical stage and severity of lymphoedema (Cramer's V of
0,73 (p < 0.001)). Differentiation was feasible between inguinal lymphatic vessel
aplasia (21%), hypoplasia (15%), normal pattern (53%) and hyperplasia (11%).
Severe lymphoedema was observed in 46% of aplasic patterns and in 37% of
hyperplasic patterns, but in only 15% of hypoplasic patterns and never observed
in normal patterns (p < 0.001). CONCLUSION: Non-contrast MR lymphography is able
to classify primary lower limb lymphoedemas into hyperplasic, aplasic, hypoplasic
and normal patterns. KEY POINTS: * Non-contrast MR lymphography is able to
classify primary lower limb lymphoedemas. * Lymphoedema can be classified in
hyperplasic, aplasic, hypoplasic and normal patterns. * Non-contrast MR
lymphography can optimize clinical management of primary lower limb lymphoedemas.
PMID- 28695358
TI - Retained executive abilities in mild cognitive impairment are associated with
increased white matter network connectivity.
AB - PURPOSE: To describe structural network differences in individuals with mild
cognitive impairment (MCI) with high versus low executive abilities, as reflected
by measures of white matter connectivity using diffusion tensor imaging (DTI).
MATERIALS AND METHODS: This was a retrospective, cross-sectional study. Of the
128 participants from the Alzheimer's Disease Neuroimaging Initiative database
who had both a DTI scan as well as a diagnosis of MCI, we used an executive
function score to classify the top 15 scoring patients as high executive ability,
and the bottom-scoring 16 patients as low executive ability. Using a regions-of
interest-based analysis, we constructed networks and calculated graph theory
measures on the constructed networks. We used automated tractography in order to
compare differences in major white matter tracts. RESULTS: The high executive
ability group yielded greater network size, density and clustering coefficient.
The high executive ability group reflected greater fractional anisotropy
bilaterally in the inferior and superior longitudinal fasciculi. CONCLUSIONS: The
network measures of the high executive ability group demonstrated greater white
matter integrity. This suggests that white matter reserve may confer greater
protection of executive abilities. Loss of this reserve may lead to greater
impairment in the progression to Alzheimer's disease dementia. KEY POINTS: * The
MCI high executive ability group yielded a larger network. * The MCI high
executive ability group had greater FA in numerous tracts. * White matter reserve
may confer greater protection of executive abilities. * Loss of executive reserve
may lead to greater impairment in AD dementia.
PMID- 28695359
TI - Radiation dose reduction for CT assessment of urolithiasis using iterative
reconstruction: A prospective intra-individual study.
AB - OBJECTIVE: To assess the performance of hybrid (HIR) and model-based iterative
reconstruction (MIR) in patients with urolithiasis at reduced-dose computed
tomography (CT). METHODS: Twenty patients scheduled for unenhanced abdominal CT
for follow-up of urolithiasis were prospectively included. Routine dose
acquisition was followed by three low-dose acquisitions at 40%, 60% and 80%
reduced doses. All images were reconstructed with filtered back projection (FBP),
HIR and MIR. Urolithiasis detection rates, gall bladder, appendix and
rectosigmoid evaluation and overall subjective image quality were evaluated by
two observers. RESULTS: 74 stones were present in 17 patients. Half the stones
were not detected on FBP at the lowest dose level, but this improved with MIR to
a sensitivity of 100%. HIR resulted in a slight decrease in sensitivity at the
lowest dose to 72%, but outperformed FBP. Evaluation of other structures with HIR
at 40% and with MIR at 60% dose reductions was comparable to FBP at routine dose,
but 80% dose reduction resulted in non-evaluable images. CONCLUSIONS: CT
radiation dose for urolithiasis detection can be safely reduced by 40 (HIR)-60
(MIR) % without affecting assessment of urolithiasis, possible extra-urinary
tract pathology or overall image quality. KEY POINTS: * Iterative reconstruction
can be used to substantially lower the radiation dose. * This allows for
radiation reduction without affecting sensitivity of stone detection. * Possible
extra-urinary tract pathology evaluation is feasible at 40-60% reduced dose.
PMID- 28695360
TI - Erratum to: Lambert-Eaton myasthenic syndrome (LEMS): a rare autoimmune
presynaptic disorder often associated with cancer.
PMID- 28695361
TI - Acute disseminated encephalomyelitis: prognostic value of early follow-up brain
MRI.
AB - Patients with acute disseminated encephalomyelitis (ADEM) are presumed to have
radiological monophasic disease, but this is uncertain since follow-up brain MRI
is not routinely performed. We aimed to ascertain combined radiological and
clinical monophasic disease in ADEM patients and to assess whether performing
early (<6 months) follow-up brain MRI has prognostic value for subsequent
multiphasic disease. We retrospectively studied the medical records of patients
initially diagnosed with ADEM (years 2000-2014) at the Massachusetts General
Hospital, USA. A neuroimaging specialist, masked to clinical events, reviewed all
available brain MRIs. We included 62 patients (25 male; 30 pediatric; median
clinical follow-up 3 years) and classified them into two subgroups: (1)
clinically monophasic (no new, recurrent or worsening neurological symptoms >3
months after onset) (n = 45), and (2) clinically multiphasic (clinical relapse >3
months after onset) (n = 17). All clinically monophasic patients with brain MRI
follow-up (n = 30) also had radiological monophasic disease a median of 2 years
after ADEM onset. New lesions (58 vs. 14%) and persistent lesions (100 vs. 18%)
on early brain MRI [available in 40 patients (65%)], as well as clinical flares
(53 vs. 20%), were more common in clinically multiphasic versus monophasic
patients. These early follow-up data allowed us to predict multiphasic disease
with reasonable accuracy in a multivariable model (AUC = 0.73). We conclude that
performing early follow-up brain MRI routinely in ADEM patients would aid
clinicians in predicting multiphasic disease and may stratify patients who would
benefit from initiation of disease-modifying therapy for multiple sclerosis.
PMID- 28695362
TI - Metabolic and kinematic parameters during walking with poles in Parkinson's
disease.
AB - In healthy people, energy expenditure is generally higher during walking with
poles (WP) than during conventional walking (W). In persons with Parkinson's
disease (PD), walking is slower and may be associated with greater energy
consumption, stride-to-stride variability, and difficulty in regulating stride
length. The aim of this study was to determine whether treadmill WP at three
different speeds could induce changes in gait kinematics and oxygen consumption
in PD patients. The study sample was 20 patients with mild-to-moderate PD and 20
age-matched healthy controls. Subjects underwent 5-min W and WP treadmill tests
at three different speeds (2.5, 3.5, and 4.5 km/h). Metabolic and gait parameters
(ventilation, gas exchange, stride count and length) were recorded. As compared
with the healthy controls, higher energy consumption (P < 0.05) (and other
metabolic parameters), shorter stride, and reduced cadence (P < 0.05) were
observed for the PD patients, independent of the walking technique. All subjects
were noted to take longer strides during WP (P < 0.001), especially at the lowest
treadmill speed. However, significantly higher energy consumption was observed
only for the healthy controls (P < 0.05). No changes in metabolic parameters
during WP were recorded; however, a substantial improvement in gait cycle length
was noted for the PD patients.
PMID- 28695363
TI - How does performance of the Friedreich Ataxia Functional Composite compare to
rating scales?
AB - Progression of Friedreich ataxia (FRDA) is often measured using neurological
rating scales such as the Friedreich Ataxia Rating Scale (FARS). Performance
scales comprising functional measures have been used in other conditions due to
their increased sensitivity and reproducibility and may replace examination-based
measures. The aims of this study were to examine the relationship between the
Friedreich Ataxia Functional Composite (FAFC) measures and characteristics of
FRDA to determine if the FAFC is more sensitive to clinical change over time
compared to its components. One hundred and twenty-two individuals completed the
timed 25-foot walk (T25FW), 9-Hole Peg Test (9HPT) and the low-contrast letter
acuity (LCLA) test at baseline, 63 at year 1, 34 at year 2 and 25 at year 3.
Composite scores, Z2 (T25FW and 9HPT) and Z3 (T25FW, 9HPT and LCLA) were created.
Correlation analyses were conducted. Change in FAFC components were examined over
1, 2, and 3 years. The FARS, Z2, Z3 and 9HPT showed significant change over all
time points compared to baseline. The T25FW only demonstrated significant change
over 3 years. The LCLA demonstrated no significant change over any of the time
points. The FAFC shows significant change over time and indicates disease
progression, however, this may result from individual components driving the
differences. The LCLA showed no change over time, rendering Z3 redundant. The
FAFC is of limited value in cohorts with non-ambulant individuals as it leads to
skewing of the dataset and is better suited to less affected populations.
PMID- 28695364
TI - Revisiting mitochondrial ocular myopathies: a study from the Italian Network.
AB - Ocular myopathy, typically manifesting as progressive external ophthalmoplegia
(PEO), is among the most common mitochondrial phenotypes. The purpose of this
study is to better define the clinical phenotypes associated with ocular
myopathy. This is a retrospective study on a large cohort from the database of
the "Nation-wide Italian Collaborative Network of Mitochondrial Diseases". We
distinguished patients with ocular myopathy as part of a multisystem
mitochondrial encephalomyopathy (PEO-encephalomyopathy), and then PEO with
isolated ocular myopathy from PEO-plus when PEO was associated with additional
features of multisystemic involvement. Ocular myopathy was the most common
feature in our cohort of mitochondrial patients. Among the 722 patients with a
definite genetic diagnosis, ocular myopathy was observed in 399 subjects (55.3%)
and was positively associated with mtDNA single deletions and POLG mutations.
Ocular myopathy as manifestation of a multisystem mitochondrial encephalomyopathy
(PEO-encephalomyopathy, n = 131) was linked to the m.3243A>G mutation, whereas
the other "PEO" patients (n = 268) were associated with mtDNA single deletion and
Twinkle mutations. Increased lactate was associated with central neurological
involvement. We then defined, among the PEO group, as "pure PEO" the patients
with isolated ocular myopathy and "PEO-plus" those with ocular myopathy and other
features of neuromuscular and multisystem involvement, excluding central nervous
system. The male proportion was significantly lower in pure PEO than PEO-plus.
This study reinforces the need for research on the role of gender in
mitochondrial diseases. The phenotype definitions here revisited may contribute
to a more homogeneous patient categorization, useful in future studies and
clinical trials.
PMID- 28695365
TI - Influence of external cooling on the femtosecond laser ablation of dentin.
AB - In the present work, the influence of external cooling on the temperature rise in
the tooth pulpal chamber during femtosecond laser ablation was investigated. The
influence of the cooling method on the morphology and constitution of the laser
treated surfaces was studied as well. The ablation experiments were performed on
dentin specimens using an Yb:KYW chirped-pulse-regenerative amplification laser
system (560 fs, 1030 nm). Cavities were created by scanning the specimens at a
velocity of 5 mm/s while pulsing the stationary laser beam at 1 kHz and with
fluences in the range of 2-14 J/cm2. The experiments were performed in air and
with surface cooling by a lateral air jet and by a combination of an air jet and
water irrigation. The temperature in the pulpal chamber of the tooth was measured
during the laser experiments. The ablation surfaces were characterized by
scanning electron microscopy (SEM) and Fourier transform infrared (FTIR)
spectroscopy. The temperature rise reached 17.5 degrees C for the treatments
performed with 14 J/cm2 and without cooling, which was reduced to 10.8 +/- 1.0
and 6.6 +/- 2.3 degrees C with forced air cooling and water cooling,
respectively, without significant reduction of the ablation rate. The ablation
surfaces were covered by ablation debris and resolidified droplets containing
mainly amorphous calcium phosphate, but the amount of redeposited debris was much
lower for the water-cooled specimens. The redeposited debris could be removed by
ultrasonication, revealing that the structure and constitution of the tissue
remained essentially unaltered. The present results show that water cooling is
mandatory for the femtosecond laser treatment of dentin, in particular, when high
fluences and high pulse repetition rates are used to achieve high material
removal rates.
PMID- 28695366
TI - Assessment of Local Adverse Reactions to Subcutaneous Immunoglobulin (SCIG) in
Clinical Trials.
PMID- 28695367
TI - Paeonol Inhibits IL-1beta-Induced Inflammation via PI3K/Akt/NF-kappaB Pathways:
In Vivo and Vitro Studies.
AB - Paeonol, the main active component isolated from the root of Paeonia
suffruticosa, has been reported to have anti-inflammatory properties. However,
the effects of paeonol on osteoarthritis (OA) remain unclear. The aim of this
study was to investigate the anti-inflammatory effects and mechanism of paeonol
in IL-1beta-induced human OA chondrocytes as well as mice OA models. Human OA
chondrocytes were pretreated with different concentrations of paeonol 2 h prior
to IL-1beta (10 ng/mL) stimulation for 24 h. Nitric oxide (NO) production was
determined by Griess method. The levels of prostaglandin E2 (PGE2), matrix
metalloproteinase 1 (MMP-1), MMP-3, and MMP-13 were assessed by ELISA. Inducible
nitric oxide synthase (INOS), COX-2, and PI3K/Akt/NF-kappaB-related signaling
molecules production were measured by Western blot. In vivo, mice OA models were
established by destabilization of the medial meniscus. One month after surgery,
mice in paeonol-treated group were given intraperitoneal injection of paeonol in
30 mg/kg every day, while mice of vehicle-treated group were injected with DMSO
under the same conditions. Hematoxylin and eosin as well as Safranin-O staining
were applied to assess the severity of cartilage lesions. The results showed that
pretreatment with paeonol could inhibit IL-1beta-induced NO and PGE2 production.
Meanwhile, the overproduction of INOS, COX-2, MMP-1, MMP-3, and MMP-13 were also
reversed by paeonol. Moreover, paeonol was found to inhibit IL-1beta-induced NF
kappaB activation, PI3K, and AKT phosphorylation. In vivo, treatment with paeonol
exhibited less cartilage degradation and lower Osteoarthritis Research Society
International scores in mice OA models. In conclusion, these results suggest that
paeonol may be a potential therapeutic agent in the treatment of OA.
PMID- 28695368
TI - An Interaction of LPS and RSV Infection in Augmenting the AHR and Airway
Inflammation in Mice.
AB - Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory
tract infection (LRTI) in children under 5 years of age, especially infants with
severe bronchiolitis. Our preliminary clinical experiments showed that bacterial
colonization was commonly observed in children with virus-induced wheezing,
particularly in those with recurrent wheezing, suggesting that bacterial
colonization with an accompanying viral infection may contribute to disease
severity. In most cases, RSV-infected infants were colonized with pathogenic
bacteria (mainly Gram-negative bacteria). LPS is the main component of Gram
negative bacteria and acts as a ligand for Toll-like receptor 4 (TLR4). Relevant
studies have reported that the TLR family is crucial in mediating the link
between viral components and immunologic responses to infection. Of note, TLR4
activation has been associated with disease severity during RSV infection. In the
present study, we identified that LPS aggravated RSV-induced AHR and airway
inflammation in BALB/c mice using an RSV coinfection model. We found that the
airway inflammatory cells and cytokines present in BALF and TRIF in lung tissue
play a role in inducing AHR and airway inflammation upon RSV and bacteria
coinfection, which might occur through the TRIF-MMP-9-neutrophil-MMP-9 signalling
pathway. These results may aid in the development of novel treatments and improve
vaccine design.
PMID- 28695369
TI - Associations between Social Support from Family, Friends, and Teachers and
depressive Symptoms in Adolescents.
AB - Approximately 20% of adolescents develop depressive symptoms. Family, friends,
and teachers are crucial sources of social support for adolescents, but it is
unclear whether social support impacts adolescents directly (principle-effect
model) or by moderating the effect of stress (stress-buffer model) and whether
each source of social support remains meaningful when their influence is studied
simultaneously. To help fill this gap, we followed 1452 Australian students
(average age at enrollment = 13.1, SD = 0.5; range: 11-16 years; 51.9% female)
for 5 years. Based on our findings, each source of support is negatively related
to depressive symptoms one year later when studied independently but when
combined, only family and teacher support predicted depressive symptoms. Family
support in all grades and teacher support in grade 8 to 10 but not in grade 11
directly impacted adolescent depressive symptoms 1 year later. Family support in
grades 8 and 11 also buffered against the negative impact of stress on depressive
symptoms one year later. Based on the unexpected findings, the most important
limitations seem to be that the used instruments do not allow for a separation of
different groups of friends (e.g., classmates, same-gender peers, romantic
partners), types of social support, and stress. In addition, the high, nonrandom
attrition rate with adolescents reporting less social support, more stressful
events, a higher frequency of depressive symptoms, and/or being of Torres Strait
Islander or Aboriginal background limits the generalizability of our findings.
Summarized, our findings demonstrate that adolescents facing stress might benefit
more from family support compared to their peers without stressful life events
and that friends may have a weaker presence in adolescent lives than expected.
PMID- 28695370
TI - Erratum to: Repeatability of [68Ga]DKFZ11-PSMA PET Scans for Detecting Prostate
specific Membrane Antigen-positive Prostate Cancer.
PMID- 28695371
TI - Binding of alphavbeta3 Integrin-Specific Radiotracers Is Modulated by Both
Integrin Expression Level and Activation Status.
AB - PURPOSE: Molecular imaging of alphavbeta3 integrin has exhibited real potential
to guide the appropriate use of anti-angiogenic therapies. However, an incomplete
understanding of the factors that influence binding of alphavbeta3 integrin
specific radiotracers currently limits their use for assessing response to
therapy in cancer patients. This study identifies two fundamental factors that
modulate uptake of these radiotracers. Procedures Experiments were performed in
prostate cancer (PC3) and glioblastoma (U87MG) cells, which differentially
express alphavbeta3 integrin. alphavbeta3 integrin-specific radiotracers were
used to investigate the effect of manipulating alphavbeta3 integrin expression or
activation in cellular binding assays. beta3 integrin and alphavbeta3 integrin
expression were measured by western blotting and flow cytometry, respectively.
The effect of select pharmacological inhibitors on alphavbeta3 integrin
activation and expression was also determined. RESULTS: Radiotracer binding was
proportional to alphavbeta3 integrin expression when it was decreased (beta3
knock-down cells) or increased, either using pharmacological inhibitors of cell
signalling or by culturing cells for different times. Studies with both small
molecule and arginine-glycine-aspartic acid (RGD)-based radiotracers revealed
increased radiotracer binding after activation of alphavbeta3 integrin with Mn2+
or talin head domain. Moreover, inhibition of fundamental signalling pathways
(mitogen-activated protein kinase kinase (MEK), Src and VEGFR2) decreased
radiotracer binding, reflecting reduced alphavbeta3 integrin activity.
CONCLUSION: Binding of small molecule ligands and radiolabelled RGD peptides is
modulated by expression and activation status of alphavbeta3 integrin.
alphavbeta3 integrin-specific radiotracers can provide otherwise inaccessible
information of the effect of signalling pathways on alphavbeta3 integrin. This
has significant implications for assessing response to anti-angiogenic therapies
in clinical studies.
PMID- 28695372
TI - Increased Expression of Translocator Protein (TSPO) Marks Pro-inflammatory
Microglia but Does Not Predict Neurodegeneration.
AB - PURPOSE: Activation of the innate immune system plays a significant role in
pathologies of the central nervous system (CNS). In order to follow disease
progression and evaluate effectiveness of potential treatments involved in
neuroinflammation, it is important to track neuroinflammatory markers in vivo
longitudinally. The translocator protein (TSPO) is used as a target to image
neuroinflammation as its expression is upregulated in reactive glial cells during
CNS pathologies. However, it remains unclear in which microglial phenotypes TSPO
levels are upregulated, as microglia can display a plethora of activation states
that can be protective or detrimental to the CNS. PROCEDURES: We assessed the
levels of TSPO transcripts in cultured microglia that were polarized into pro-
and anti-inflammatory states in vitro and in the brain of mice in which an anti
inflammatory environment was induced in vivo. In addition, we used a mouse model
of peroxisomal multifunctional protein-2 (MFP2) deficiency that exhibits
widespread neuroinflammation despite no neuronal loss and monitored TSPO
expression by immunohistochemistry and by imaging using the TSPO radiotracer
[18F]DPA-714. RESULTS: TSPO expression was selectively increased in so-called
classically activated or M1 microglia but not in alternatively activated or M2
microglia in vitro. In agreement, TSPO transcript levels were not induced in an
anti-inflammatory brain environment. We found that both transcript and protein
levels of TSPO are significantly increased in the brain of Mfp2 -/- compared to
those of the control mice and TSPO immunoreactivity colocalized predominantly
with microglia in Mfp2 -/- brain. In vitro and ex vivo autoradiography in Mfp2 -/
mice using the TSPO radiotracer [18F]DPA-714 confirmed increased expression of
TSPO. These data demonstrate that TSPO imaging reveals microgliosis in non
neurodegenerative brain pathologies. CONCLUSIONS: We show that induced TSPO
expression marks a pro-inflammatory brain environment that is not necessarily
accompanied by neuronal loss.
PMID- 28695373
TI - Catheter ablation of persistent atrial fibrillation : Circumferential pulmonary
vein ablation: beneficial effect of an additional linear lesion at the roof of
the left atrium on the long-term outcome.
AB - BACKGROUND: Circumferential pulmonary vein ablation is still the standard
approach in patients with persistent atrial fibrillation. However, the results
are not very favourable and more complex ablation strategies are the subject of
current controversy. Therefore, we have evaluated the effect of an additional
linear lesion at the roof of the left atrium on the long-term outcome. METHODS: A
total of 125 patients with symptomatic persistent atrial fibrillation underwent a
circumferential pulmonary vein ablation procedure in combination with an
additional linear lesion at the roof of the left atrium (group A). The long-term
follow-up data was compared to 125 patients with similar clinical characteristics
who underwent circumferential pulmonary vein ablation without an additional
linear lesion at the roof of the left atrium (group B). RESULTS: The ablation
procedure could be performed as planned in all 250 patients. Three years after
catheter ablation, the success rate was 72.0% (no arrhythmia recurrence in 90 out
of 125 patients) in group A and 63.2% in group B (no arrhythmia recurrence in 79
out of 125 patients; P = 0.04). There were no major complications. CONCLUSIONS:
Catheter ablation of persistent atrial fibrillation comprising a circumferential
pulmonary vein ablation and an additional linear lesion at the roof of the left
atrium provides more favourable long-term results than circumferential pulmonary
vein ablation alone.
PMID- 28695374
TI - Impact of aromaticity on anticancer activity of polypyridyl ruthenium(II)
complexes: synthesis, structure, DNA/protein binding, lipophilicity and
anticancer activity.
AB - With the aim of assessing how the aromaticity of the inert chelating ligand can
influence the activity of ruthenium(II) polypyridyl complexes, two new
monofunctional ruthenium(II) complexes, [Ru(Cl-Ph-tpy)(phen)Cl]Cl (1) and [Ru(Cl
Ph-tpy)(o-bqdi)Cl]Cl (2) (where Cl-Ph-tpy = 4'-(4-chlorophenyl)-2,2':6',2"
terpyridine, phen = 1,10-phenanthroline, o-bqdi = o-benzoquinonediimine), were
synthesized. All complexes were fully characterized by elemental analysis and
spectroscopic techniques (IR, UV-Vis, 1D and 2D NMR, XRD). Their chemical
behavior in aqueous solution was studied by UV-Vis and NMR spectroscopy showing
that both compounds are relatively labile leading to the formation of the
corresponding aqua species 1a and 2a. 1H NMR spectroscopy studies performed on
complexes 1 and 2 demonstrated that after the hydrolysis of the Cl ligand, they
are capable to interact with guanine derivatives (i.e., 9-methylguanine (9MeG)
and 5'-GMP) through the N7, forming monofunctional adduct. The kinetics and the
mechanism of the reaction of complexes 1 and 2 with the biologically more
relevant 5'-GMP ligand were studied by UV-Vis spectroscopy. DNA/protein
interactions of the complexes have been examined by photophysical studies, which
demonstrated a bifunctional binding mode of the complexes with DNA and the
complexes strongly quench the fluorescence intensity of bovine serum albumin
(BSA) through the mechanism of both static and dynamic quenching. Complexes 1 and
2 strongly induced apoptosis of treated cancer cells with high percentages of
apoptotic cells and negligible percentage of necrotic cells. In addition, both
ruthenium complexes decreased Bcl-2/Bax ratio causing cytochrome c mitochondrial
release, the activation of caspase-3 and induction of apoptosis.
PMID- 28695375
TI - Rigor of non-dairy galactose restriction in early childhood, measured by
retrospective survey, does not associate with severity of five long-term outcomes
quantified in 231 children and adults with classic galactosemia.
AB - One of many vexing decisions faced by parents of an infant with classic
galactosemia (CG) is how carefully to restrict non-dairy galactose from their
growing child's diet. Until recently, many experts recommended vigorous lifelong
dietary restriction of milk and all high-galactose dairy products as well as some
non-dairy sources of galactose such as legumes and specific fruits and
vegetables. Recently, experts have begun to relax their recommendations. The new
recommendations, that restrict only high galactose dairy products, were made in
the face of uncertainty, however, because no sufficiently powered study had been
reported testing for possible association between rigor of non-dairy galactose
restriction and severity of long-term outcomes in CG. Here we describe the
largest study of diet and outcomes in CG reported to date, conducted using
information gathered from 231 patients with CG and 71 unaffected sibling
controls. We compared rigor of dietary galactose restriction, measured using a 4
point scale by a retrospective parent-response survey, with outcomes including
growth, adaptive behaviors, receipt of speech therapy, receipt of special
educational services, and for girls and women, a plasma marker of ovarian
function (AMH). Our results confirmed the expected differences between patients
and controls, but among patients showed no significant association between rigor
of non-dairy galactose restriction in early childhood and any of the outcomes
quantified. Indeed, some weak associations were seen suggesting that rigorous
restriction of non-dairy galactose may be deleterious rather than beneficial.
Despite limitations, these findings support the ongoing trend toward diet
liberalization with regard to non-dairy sources of galactose for children and
adults with classic galactosemia.
PMID- 28695376
TI - Heterozygous carriers of succinyl-CoA:3-oxoacid CoA transferase deficiency can
develop severe ketoacidosis.
AB - Succinyl-CoA:3-oxoacid CoA transferase (SCOT, gene symbol OXCT1) deficiency is an
autosomal recessive disorder in ketone body utilization that results in severe
recurrent ketoacidotic episodes in infancy, including neonatal periods. More than
30 patients with this disorder have been reported and to our knowledge, their
heterozygous parents and siblings have had no apparent ketoacidotic episodes.
Over 5 years (2008-2012), we investigated several patients that presented with
severe ketoacidosis and identified a heterozygous OXCT1 mutation in four of these
cases (Case1 p.R281C, Case2 p.T435N, Case3 p.W213*, Case4 c.493delG). To confirm
their heterozygous state, we performed a multiplex ligation-dependent probe
amplification analysis on the OXCT1 gene which excluded the presence of large
deletions or insertions in another allele. A sequencing analysis of subcloned
full-length SCOT cDNA showed that wild-type cDNA clones were present at
reasonable rates to mutant cDNA clones. Over the following 2 years (2013-2014),
we analyzed OXCT1 mutations in six more patients presenting with severe
ketoacidosis (blood pH ?7.25 and total ketone body ?10 mmol/L) with non-specific
urinary organic acid profiles. Of these, a heterozygous OXCT1 mutation was found
in two cases (Case5 p.G391D, Case6 p.R281C). Moreover, transient expression
analysis revealed R281C and T435N mutants to be temperature-sensitive. This
characteristic may be important because most patients developed ketoacidosis
during infections. Our data indicate that heterozygous carriers of OXCT1
mutations can develop severe ketoacidotic episodes in conjunction with ketogenic
stresses.
PMID- 28695377
TI - Ventricular dyssynchrony assessment using ultra-high frequency ECG technique.
AB - PURPOSE: The aim of this proof-of-concept study is to introduce new high-dynamic
ECG technique with potential to detect temporal-spatial distribution of
ventricular electrical depolarization and to assess the level of ventricular
dyssynchrony. METHODS: 5-kHz 12-lead ECG data was collected. The amplitude
envelopes of the QRS were computed in an ultra-high frequency band of 500-1000 Hz
and were averaged (UHFQRS). UHFQRS V lead maps were compiled, and numerical
descriptor identifying ventricular dyssynchrony (UHFDYS) was detected. RESULTS:
An electrical UHFQRS maps describe the ventricular dyssynchrony distribution in
resolution of milliseconds and correlate with strain rate results obtained by
speckle tracking echocardiography. The effect of biventricular stimulation is
demonstrated by the UHFQRS morphology and by the UHFDYS descriptor in selected
examples. CONCLUSIONS: UHFQRS offers a new and simple technique for assessing
electrical activation patterns in ventricular dyssynchrony with a temporal
spatial resolution that cannot be obtained by processing standard surface ECG.
The main clinical potential of UHFQRS lies in the identification of differences
in electrical activation among CRT candidates and detection of improvements in
electrical synchrony in patients with biventricular pacing.
PMID- 28695378
TI - Macular ganglion cell-inner plexiform layer thickness for detection of early
retinal toxicity of hydroxychloroquine.
AB - PURPOSE: This study evaluated the macular ganglion cell-inner plexiform layer (GC
IPL) thickness using spectral-domain (SD) optical coherence tomography (OCT) in
patients with chronic exposure to hydroxychloroquine (HCQ). METHODS: A total of
90 patients (90 eyes) treated with HCQ for at least 5 years and normal controls
were included in the study. A fundus examination, automated threshold perimetry,
and GC-IPL thickness measurements using the Cirrus high-definition OCT ganglion
cell analysis algorithm were performed in all patients treated with HCQ. Average,
minimum, and sectorial macular GC-IPL thicknesses were compared between the
patients and controls. RESULTS: There was no statistically significant difference
in age or sex between the groups. The anterior segment and fundoscopy were normal
in all patients and controls. Visual field (VF) testing was normal in all
patients. The average, minimum, and sectorial macular GC-IPL thicknesses were
significantly lower in patients than those in control subjects. CONCLUSIONS:
There was significant thinning of the macular GC-IPL in the absence of clinically
evident HCQ-related retinopathy and VF abnormalities. Measurements of the macular
GC-IPL thickness using SD-OCT may therefore be useful in the early diagnosis and
in monitoring the progression of retinal changes in patients receiving long-term
HCQ therapy.
PMID- 28695379
TI - Expression of prostaglandin E2 receptor subtypes in human pterygium and normal
conjunctiva: immunohistochemical study.
AB - PURPOSE: In the present study, we aimed to evaluate the expression of EP
receptors in primary and recurrent human pterygium tissues. METHODS: Pterygium
samples were collected from 65 patients with primary pterygium and 16 patients
with recurrent pterygium. Normal conjunctival tissues were collected from nasal
interpalpebral area from 17 patients without systemic and any other ocular
pathology. Expression of EP receptors was evaluated by immunohistochemistry. The
median value for each receptor staining score (RSS) was determined in normal
conjunctival specimens. In this study, RSS of > median value was defined as
positive staining or high expression and <= median value as negative staining or
weak expression in specimens. Chi-square test was used for statistical analysis,
and p value of less than 0.05 was considered significant. RESULTS: Stromal
expression of EP1 was significantly higher in primary and recurrent pterygium
specimens compared to normal conjunctival tissues (p = 0.007 and p = 0.002,
respectively). Epithelial expressions of EP2 and EP3 were significantly lower in
primary pterygium specimens compared to normal conjunctival tissues (p = 0.005
and p < 0.0001, respectively), and stromal expressions were insignificant.
Stromal expression of EP4 was significantly higher in primary and recurrent
pterygium specimens compared to normal conjunctival tissues (p = 0.002 and p =
0.012, respectively). CONCLUSIONS: Expression of EP receptors has been up- or
downregulated in primary and recurrent pterygium tissues, and these receptors may
play a role in formation and recurrence of pterygium.
PMID- 28695380
TI - Macular capillary recovery in systemic lupus erythematosus complicated by Kikuchi
Fujimoto disease.
AB - PURPOSE: Few case reports have described vaso-occlusive retinopathy in systemic
lupus erythematosus (SLE) using optical coherence tomography (OCT) angiography.
Here we report the clinical features of a patient with SLE, complicated by
Kikuchi-Fujimoto disease, who developed vaso-occlusive retinopathy. We then
describe the subsequent recovery of the macular capillaries as assessed by OCT
angiography. CASE: A 16-year-old male was referred to us with fever, a 1-month
history of violaceous red papules and erythematous plaques on his face and a
painful nodule in his right neck. We diagnosed him with SLE complicated by
Kikuchi-Fujimoto disease through physiological assessment and histology from his
neck lymph node and chin skin. Systemic steroids were prescribed as treatment.
After remission, his fever and cervical lymph node swelling with pain recurred
and he developed blurred inferior vision in his left eye. His best-corrected
visual acuities were 1.0 and 0.1 in the right and left eyes, respectively.
Extensive cotton wool spots were observed in the right fundus, and retinal
capillary occlusions were detected by OCT angiography of the left eye. We
diagnosed this case as vaso-occlusive retinopathy with SLE and increased
immunosuppressive treatment together with anticoagulation therapy. Macular
capillaries, observed by OCT angiography, gradually recovered function following
assessment at 7 and 16 months post-onset of the vaso-occlusive retinopathy.
CONCLUSIONS: We reported a 11/2-year course of vaso-occlusive retinopathy in a
patient with SLE complicated by Kikuchi-Fujimoto disease. Occlusion of the
retinal vasculature and the subsequent recovery of circulation are clearly
observed by OCT angiography.
PMID- 28695381
TI - Development of a method to assess the ichthyotoxicity of the harmful marine
microalgae Karenia spp. using gill cell cultures from red sea bream (Pagrus major
).
AB - The present study reports the development of a method to investigate
ichthyotoxicity of harmful marine microalgae using cultured red sea bream (Pagrus
major) gill cells. The cultured gill cells formed adherent 1-2 layers on the
bottom of the culture plate and could tolerate seawater exposure for 4 h without
significant alteration in cell survival. The microalgae Karenia mikimotoi,
Karenia papilionacea, K. papilionacea phylotype-I, and Heterosigma akashiwo were
cultured, then directly exposed to gill cells. After K. mikimotoi and K.
papilionacea phylotype-I exposure, live cell coverage was significantly lower
than in the cells exposed to a seawater-based medium (control cells; P < 0.05).
Toxicity of K. mikimotoi cells was weakened when cells were ruptured, and was
almost inexistent when the algal cells were removed from the culture by
filtration. Significant cytotoxicity was detected in the concentrated ruptured
cells, and in the concentrated of ruptured cells after freezing and thawing
though cytotoxicity was weakened; whereas, cytotoxicity almost disappeared after
heat treatment. In addition, examination of the distribution of toxic substances
from the ruptured cells showed that cytotoxicity mainly occurred in the fraction
with the resuspended pellet after centrifugation at 3000*g.
PMID- 28695382
TI - Point-of-care coagulation monitoring: first clinical experience using a paper
based lateral flow diagnostic device.
AB - Vitamin K antagonists such as warfarin are the most widely used class of oral
anticoagulants. Due to a narrow therapeutic window, patients on warfarin require
regular monitoring. Self-testing using point-of-care (POC) diagnostic devices is
available, but cost makes this monitoring method beyond reach for many. The main
objective of this research was to assess the clinical utility of a low-cost,
paper-based lateral flow POC diagnostic device developed for anticoagulation
monitoring without the need for a separate electronic reader. Custom-fabricated
lateral flow assay (LFA) test strips comprised of a glass fiber sample pad, a
nitrocellulose analytical membrane, a cellulose wicking pad, and a plastic
backing card were assembled in a plastic cassette. Healthy volunteers and
patients on warfarin therapy were recruited for this prospective study. For each
participant, a whole blood sample was collected via fingerstick to determine: (1)
international normalized ratio (INR) using the CoaguChek(r) XS coagulometer, (2)
hematocrit by centrifugation, and (3) red blood cell (RBC) travel distance on the
experimental LFA device after 240 s using digital image analysis. RBC travel
distance measured on the LFA device using blood samples obtained from warfarin
patients positively correlated with increasing INR value and the LFA device had
the capability to statistically distinguish between healthy volunteer INR values
and those for patients groups with INR >= 2.6. From these data, it is predicted
that this low-cost, paper-based LFA device can have clinical utility for
identifying anticoagulated patients taking vitamin K antagonists who are outside
of the desired therapeutic efficacy window.
PMID- 28695383
TI - Dietary Advanced Glycation End Products and Cardiometabolic Risk.
AB - PURPOSE OF REVIEW: This report analyzes emerging evidence about the role of
dietary advanced glycation end products (AGEs) as a cardiometabolic risk factor.
Two important aspects are discussed: First, the modulation of AGE load by dietary
AGEs; second, if the evidence of clinical and observational studies is enough to
make dietary recommendations towards lowering AGE intake. RECENT FINDINGS:
Clinical studies in subjects with diabetes mellitus have shown that high intake
of dietary AGEs increases inflammation markers, oxidative stress, and could
impair endothelial function. In subjects at risk for cardiometabolic diseases
(with overweight, obesity, or prediabetes), dietary AGE restriction decreases
some inflammatory molecules and improves insulin sensitivity. However, studies in
healthy subjects are limited, and not all of the studies have shown a decrease in
circulating AGEs. Therefore, it is still unclear if dietary AGEs represent a
health concern for people potentially at risk for cardiometabolic diseases. The
evidence shows that dietary AGEs are bioavailable and absorbed, and the rate of
excretion depends on dietary intake. The metabolic fate of most dietary AGEs
remains unknown. Regardless, most studies have shown that by diminishing AGE
intake, circulating levels will also decrease. Thus, dietary AGEs can modulate
the AGE load at least in patients with DM, overweight, or obesity. Studies with
specific clinical outcomes and large-scale observational studies are needed for a
better risk assessment of dietary AGEs and to establish dietary recommendations
accordingly.
PMID- 28695384
TI - Carbonic Anhydrase Inhibitors Induce Developmental Toxicity During Zebrafish
Embryogenesis, Especially in the Inner Ear.
AB - In vertebrates, carbonic anhydrases (CAs) play important roles in ion transport
and pH regulation in many organs, including the eyes, kidneys, central nervous
system, and inner ear. In aquatic organisms, the enzyme is inhibited by various
chemicals present in the environment, such as heavy metals, pesticides, and
pharmaceuticals. In this study, the effects of CA inhibitors, i.e., sulfonamides
[ethoxyzolamide (EZA), acetazolamide (AZA), and dorzolamide (DZA)], on zebrafish
embryogenesis were investigated. In embryos treated with the sulfonamides,
abnormal development, such as smaller otoliths, an enlarged heart, an irregular
pectoral fin, and aberrant swimming behavior, was observed. Especially, the
development of otoliths and locomotor activity was severely affected by all the
sulfonamides, and EZA was a consistently stronger inhibitor than AZA or DZA. In
the embryos treated with EZA, inner ear hair cells containing several CA
isoforms, which provide HCO3- to the endolymph for otolith calcification and
maintain an appropriate pH there, were affected. Acridine orange/ethidium bromide
staining indicated that the hair cell damage in the inner ear and pectral fin is
due to apoptosis. Moreover, RNA measurement demonstrated that altered gene
expression of cell cycle arrest- and apoptosis-related proteins p53, p21, p27,
and Bcl-2 occurred even at 0.08 ppm with which normal development was observed.
This finding suggests that a low concentration of EZA may affect embryogenesis
via the apoptosis pathway. Thus, our findings demonstrated the importance of
potential risk assessment of CA inhibition, especially regarding the formation of
otoliths as a one of the most sensitive organs in embryogenesis.
PMID- 28695385
TI - Recovery of Previously Uncultured Bacterial Genera from Three Mediterranean
Sponges.
AB - Sponges often harbour a dense and diverse microbial community. Presently, a large
discrepancy exists between the cultivable bacterial fraction from sponges and the
community in its natural environment. Here, we aimed to acquire additional
insights into cultivability of (previously uncultured) bacteria from three sponge
species, namely Aplysina aerophoba, Corticium candelabrum and Petrosia
ficiformis, by studying bacterial growth on five media in the form of 60
communities scraped from plates without antibiotics, as well as in the form of
individual isolates that were grown on these media supplemented with antibiotics.
We applied (double-)barcoded 16S ribosomal RNA (rRNA) gene amplicon sequencing
for species identification. We show that previously uncultured bacteria can be
cultivated using conventional plating and that application of antibiotics in the
media can serve to capture a greater bacterial diversity. Moreover, we present
criteria to address an important caveat of the plate scraping method whereby
bacteria may be detected that did not actually grow. Fourteen out of 27
cultivated novel taxa (<95% identity of the 16S rRNA gene amplicon to reported
species) belong to Actinobacteria, which indicates the presence of a large
untapped reservoir of bioactive compounds. Three Flavobacteriaceae spp. were
isolated that potentially constitute two new genera and one new species.
PMID- 28695386
TI - A homomeric geranyl diphosphate synthase-encoding gene from Camptotheca acuminata
and its combinatorial optimization for production of geraniol in Escherichia
coli.
AB - Geranyl diphosphate (GPP), the unique precursor for all monoterpenoids, is
biosynthesized from isopentenyl diphosphate and dimethylallyl diphosphate via the
head-to-tail condensation reaction catalyzed by GPP synthase (GPPS). Herein a
homomeric GPPS from Camptotheca acuminata, a camptothecin-producing plant, was
obtained from 5'- and 3'-rapid amplification of cDNA ends and subsequent overlap
extension and convenient PCR amplifications. The truncate CaGPPS was introduced
to replace ispA of pBbA5c-MevT(CO)-MBIS(CO, ispA), a de novo biosynthetic
construct for farnesyl diphosphate generation, and overexpressed in Escherichia
coli, together with the truncate geraniol synthase-encoding gene from C.
acuminata (tCaGES), to confirm CaGPPS-catalyzed reaction in vivo. A 24.0 +/- 1.3
mg L-1 of geraniol was produced in the recombinant E. coli. The production of GPP
was also validated by the direct UPLC-HRMSE analyses. The tCaGPPS and tCaGES
genes with different copy numbers were introduced into E. coli to balance their
catalytic potential for high-yield geraniol production. A 1.6-fold increase of
geraniol production was obtained when four copies of tCaGPPS and one copy of
tCaGES were introduced into E. coli. The following fermentation conditions
optimization, including removal of organic layers and addition of new n-decane,
led to a 74.6 +/- 6.5 mg L-1 of geraniol production. The present study suggested
that the gene copy number optimization, i.e., the ratio of tCaGPPS and tCaGES,
plays an important role in geraniol production in the recombinant E. coli. The
removal and addition of organic solvent are very useful for sustainable high
yield production of geraniol in the recombinant E. coli in view of that the
solubility of geraniol is limited in the fermentation broth and/or n-decane.
PMID- 28695387
TI - The Role of Leaf Volatiles of Ludwigia octovalvis (Jacq.) Raven in the Attraction
of Altica cyanea (Weber) (Coleoptera: Chrysomelidae).
AB - Larvae and adults of Altica cyanea (Weber) (Coleoptera: Chrysomelidae) feed on
the rice-field weed Ludwigia octovalvis (Jacq.) Raven (Onagraceae), commonly
known as willow primrose, which is considered a biocontrol agent of the weed.
Volatile organic compounds from undamaged plants, plants after 4, 12, and 36 h of
continuous feeding by A. cyanea larvae or adult females and after mechanical
damaging were identified by GC-MS and GC-FID analyses. Twenty nine compounds were
identified from undamaged plants. 2Z-Penten-1-ol, geraniol, and 1-tridecanol were
present in all plants damaged by larvae. In contrast, feeding by adults caused
the release of 2Z-penten-1-ol only after 12 and 36 h; whereas geraniol and 1
tridecanol appeared only after 36 h. Farnesyl acetone was detected after 12 and
36 h of feeding by larvae and after 36 h of feeding by adults. Farnesene was
detected after 36 h of feeding by larvae and adults. Linalool was unique after 36
h of feeding by larvae. In Y-shaped glass tube olfactometer bioassays, A. cyanea
females were attracted to volatiles after 36 h of feeding by larvae or adults
compared to volatiles released by undamaged plants. The insects were attracted to
five synthetic compounds: 3-hexanol, alpha-pinene, linalool oxide, geraniol, and
phytol. Synthetic blends were more attractive than individual compounds. Compared
to undamaged plants, volatiles released by plants, damaged by conspecific
individuals, were more attractive to A. cyanea females, due to elevated emissions
of 3-hexanol, alpha-pinene, linalool oxide, geraniol, and phytol.
PMID- 28695388
TI - Measuring Acceptability and Preferences for Implementation of Pre-Exposure
Prophylaxis (PrEP) Using Conjoint Analysis: An Application to Primary HIV
Prevention Among High Risk Drug Users.
AB - Although people who use drugs (PWUD) are one of the key risk populations who
could benefit from the use of pre-exposure prophylaxis (PrEP), to date, little
attention has been given to incorporating PrEP into HIV prevention approaches
targeting this underserved group. This study investigated the acceptability of
PrEP based on a number of known PrEP attributes among high-risk PWUD in a drug
treatment setting. A total of 400 HIV-negative PWUD, who reported drug- and/or
sex-related risk behaviors were recruited from a methadone clinic to complete a
stated preference (full-profile conjoint) survey. Participants ranked the eight
hypothetical PrEP program scenarios with varied combinations of six attributes
related to PrEP (cost, dosing, efficacy, side-effects, treatment setting, and
frequency of HIV testing). SPSS conjoint procedure was used to estimate the
relative importance of each attribute and preferences across eight possible PrEP
delivery programs. PrEP acceptability ranged from 30.6 to 86.3% with a mean
acceptability of 56.2% across the eight hypothetical PrEP program scenarios. The
PrEP program scenario with the highest acceptability had the following attribute
levels: insurance covered, daily dosing, 95% effective, no side-effects,
treatment at HIV clinic, and HIV testing needed every 6 months. The cost
associated with PrEP was the most important attribute (relative importance score:
RIS = 38.8), followed by efficacy (RIS = 20.5) and side effects (RIS = 11.9);
other attributes had no significant effect. Our findings reported a high
acceptability of PrEP in response to different PrEP program scenarios with
different attribute profiles. As the result of having this information,
researchers and policymakers will be better equipped for evidence informed
targeting and dissemination efforts to optimize PrEP uptake among this
underserved population.
PMID- 28695389
TI - Clinicopathological Determinants of an Elevated Systemic Inflammatory Response
Following Elective Potentially Curative Resection for Colorectal Cancer.
AB - INTRODUCTION: The postoperative systemic inflammatory response (SIR) is related
to both long- and short-term outcomes following surgery for colorectal cancer.
However, it is not clear which clinicopathological factors are associated with
the magnitude of the postoperative SIR. The present study was designed to
determine the clinicopathological determinants of the postoperative systemic
inflammatory response following colorectal cancer resection. METHODS: Patients
with a histologically proven diagnosis of colorectal cancer who underwent
elective, potentially curative resection during a period from 1999 to 2013 were
included in the study (n = 752). Clinicopathological data and the postoperative
SIR, as evidenced by postoperative Glasgow Prognostic Score (poGPS), were
recorded in a prospectively maintained database. RESULTS: The majority of
patients were aged 65 years or older, male, were overweight or obese, and had an
open resection. After adjustment for year of operation, a high day 3 poGPS was
independently associated with American Society of Anesthesiologists (ASA) grade
(hazard ratio [HR] 1.96; confidence interval [CI] 1.25-3.09; p = 0.003), body
mass index (BMI) (HR 1.60; CI 1.07-2.38; p = 0.001), mGPS (HR 2.03; CI 1.35-3.03;
p = 0.001), and tumour site (HR 2.99; CI 1.56-5.71; p < 0.001). After adjustment
for year of operation, a high day 4 poGPS was independently associated with ASA
grade (HR 1.65; CI 1.06-2.57; p = 0.028), mGPS (HR 1.81; CI 1.22-2.68; p =
0.003), NLR (HR 0.50; CI 0.26-0.95; p = 0.034), and tumour site (HR 2.90; CI 1.49
5.65; p = 0.002). CONCLUSIONS: ASA grade, BMI, mGPS, and tumour site were
consistently associated with the magnitude of the postoperative systemic
inflammatory response, evidenced by a high poGPS on days 3 and 4, in patients
undergoing elective potentially curative resection for colorectal cancer.
PMID- 28695390
TI - Impact of Patient Age on the Postoperative Survival in Pancreatic Head Cancer.
AB - BACKGROUND: Some reports have stated that pancreatoduodenectomy for elderly
patients have comparable morbidity and mortality to that of young patients.
However, the long-term outcomes of these patients have not been fully evaluated,
especially for pancreatic head cancer. METHODS: A total of 227 patients who
underwent pancreatoduodenectomy for pancreatic head cancer between 2007 and 2014
were included. They were stratified according to age: young (<70 years), elderly
(70 to <80 years), and very elderly (>=80 years). The short- and long-term
outcomes were evaluated. RESULTS: There were no significant differences in terms
of morbidity among the three groups. The median disease-free survival times were
15 months in the young, 11 months in the elderly, and 7 months in the very
elderly. The disease-free survival of the young patients was significantly better
than that in both the elderly and the very elderly (p = 0.012 and p = 0.016). The
median overall survival times were 30 months in the young, 20 months in the
elderly, and 14 months in the very elderly. The overall survival of the young
patients was significantly better than that in both the elderly and the very
elderly (p = 0.007 and p < 0.001). The difference was marginal between the
elderly and the very elderly (p = 0.053). Multivariate analysis revealed that
lymph node metastasis (p < 0.001), age >=80 years (p = 0.013), lack of adjuvant
chemotherapy (p = 0.003), blood transfusion (p = 0.015), and CA 19-9 >=300 U/ml
(p = 0.040) were significant prognostic factors. CONCLUSIONS: Patient age
influenced the survival after pancreatoduodenectomy for pancreatic cancer.
PMID- 28695391
TI - Challenging the principle of utility as a barrier for wider use of liver
transplantation for hepatocellular cancer.
AB - BACKGROUND: Although transplant benefit appears superior for patients with
advanced hepatocellular cancer (HCC), liver transplantation remains limited to
selected low-risk HCC patients to keep their outcomes similar to heterogeneous
group of non-HCC patients. The purpose of this study was to assess the rationale
for current policy of restricting access to liver transplantation to minority of
HCC patients based on utility principle. METHODS: This retrospective cohort study
comprised 1246 liver transplant recipients, including 206 HCC and 1040 non-HCC
patients. Patient survival was the primary outcome measure. Patients with HCC and
benign diseases were divided into low-, moderate-, and high-risk subgroups basing
on independent risk factors for disease-free survival and model for end-stage
liver disease (MELD) score (<30, 30-40, >40), respectively. RESULTS: MELD (p <
0.001) and presence of HCC (p = 0.008) were independent risk factors for early
and late mortality, respectively. Total tumor volume (p = 0.008) and alpha
fetoprotein (p = 0.013) were independent predictors of recurrence and mortality
used for division of HCC patients into low-, moderate-, and high-risk subgroups,
with disease-free survival rates of 74.9% (5 years), 51.7% (5 years), and 8.0% (3
years), respectively (p < 0.001). There were no differences in 5-year overall
survival between low-risk HCC (74.9%) and non-HCC (81.9%) patients (p = 0.210),
moderate-risk HCC (63.3%) and non-HCC (68.0%) patients (p = 0.372), and high-risk
HCC (55.0%) and non-HCC (56.0%) patients (p = 0.559). CONCLUSIONS: The principle
of utility is unequally applied for restriction of access to liver
transplantation for HCC patients. The results provide rationale for discussion on
reinitiation of liver transplantation for advanced HCCs.
PMID- 28695392
TI - Patterns and Drivers of Costs for Neuroendocrine Tumor Care: A Comparative
Population-Based Analysis.
AB - BACKGROUND: Little is known about resource use in the care of neuroendocrine
tumors (NETs). This study defined patterns of costs in NET management and
compared them with those of a more common malignancy, colon cancer (CC). METHODS:
Using a provincial cancer registry (2004-2012), NET patients were identified and
matched at a ratio of 1-3 with CC patients. Four phases of care were examined:
pre-diagnostic (PreDx: -2 years to -181 days), diagnostic (Dx: -180 days to +180
days), postdiagnostic (PostDx: +181 days to +3 years), and prolonged post
diagnostic (PPostDx: +181 days to +9 years). The mean costs per patient were
compared, and cost predictors were analyzed with quintile regression. RESULTS: Of
3827 NETs, 3355 were matched with 9320 CCs. The PreDx mean NET costs were higher
than the CC costs ($5877 vs $5368; p = 0.06), driven by nondrug costs. They were
lower in the Dx and PostDx phases (both p < 0.01). For PPostDx, the drug costs
were higher for NETs ($26,788 vs $7827; p < 0.01), representing 41% of the costs
versus 16% of the costs for CC. Older age and comorbidities predicted higher NET
costs in all phases. Lower socioeconomic status (SES) predicted higher costs in
the initial phases and higher SES costs in the PPost-Dx phase. Gastroenteric NETs
were associated with lower costs in the Dx phase [parameter estimate (PE),
$13,644] and pancreatic NETs with higher costs in PostDx phase (PE, $3348).
CONCLUSION: Currently, NETs represent a potential important health care burden.
The NET cost patterns differed from those for CC, with the highest costs during
the PPostDx phase. The SES and primary NET site affected costs differently at
different time points. These data can inform resource allocation tailored to the
needs for NETs.
PMID- 28695393
TI - The Prognostic Impact of Determining Resection Margin Status for Multiple
Colorectal Metastases According to the Margin of the Largest Lesion.
AB - BACKGROUND: Although the prognostic role of surgical margin status after
resection of colorectal liver metastasis (CRLM) has been previously examined,
controversy still surrounds the importance of surgical margin status in patients
with multiple tumors. METHODS: Patients who underwent curative-intent surgery for
CRLM from 2000 to 2015 and who presented with multiple tumors were identified.
Patients with R1 resection status determined by the closest resection margin of
the non-largest tumor were classified as R1-Type 1; patients with R1 status
determined by the resection margin of the largest tumor were defined as R1-Type
2. Data regarding surgical margin status, size of tumors, and overall survival
(OS) were collected and assessed. RESULTS: A total of 251 patients met inclusion
criteria; 156 patients (62.2%) had a negative margin (R0), 50 had an R1-type 1
(19.9%), and 45 had an R1-type 2 (17.9%) margin. Median and 5-year OS in the
entire cohort was 56.4 months and 48.0%, respectively. When all R1 (Type 1 + Type
2) patients were compared with R0 patients, an R1 was not associated with worse
prognosis (P = 0.05). In contrast, when R1-type 2 patients were compared with R0
patients, an R1 was strongly associated with worse OS (P = 0.009). On
multivariate analysis, although the prognostic impact of all R1 was not
associated with OS (hazard ratio [HR] 1.56; P = 0.08), R1-Type 2 margin status
independently predicted a poor outcome (HR 1.93; P = 0.03). CONCLUSIONS: The
impact of margin status varied according to the size of the tumor assessed. While
R1 margin status defined according to the non-largest tumor was not associated
with OS, R1 margin status relative to the largest index lesion was associated
with prognosis.
PMID- 28695394
TI - Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for
Moderately and Poorly Differentiated Appendiceal Adenocarcinoma: Survival
Outcomes and Patient Selection.
AB - BACKGROUND: Moderately and poorly differentiated adenocarcinoma of the appendix
represents an aggressive histological variant with a high risk of recurrence and
death. METHODS: Overall, 178 patients with moderately and poorly differentiated
appendiceal adenocarcinoma were identified from a prospective database. Clinical,
pathologic, and treatment factors were analyzed for outcomes. RESULTS: Diagnostic
laparoscopy (DL) identified radiographic occult peritoneal metastasis in 25 (42%)
patients. These patients had a significantly lower peritoneal carcinomatosis
index (PCI) and improved overall survival (OS) compared with those with
radiographic disease. Twenty-seven (41%) patients were excluded from
cytoreductive surgery (CRS) because of findings on DL, while 116 (65%) patients
underwent CRS and hyperthermic intraperitoneal chemotherapy (HIPEC), with a
median disease-free survival (DFS) of 23 months. Mucinous histology (hazard ratio
[HR] 0.52, p = 0.04) and PCI (HR 1.054, p = 0.02) were independent predictors of
DFS. The median OS following CRS and HIPEC was 48 months. Mucinous histology (HR
0.352, p = 0.018), signet ring cells (HR 3.34, p = 0.02), positive peritoneal
cytology (HR 0.081, p = 0.04), and PCI (HR 1.076, p = 0.004) were independently
associated with OS. Eight-five (73.3%) patients received neoadjuvant
chemotherapy, and 40 (47.1%) patients achieved a radiographic response; 36
(42.3%) had stable disease, while 9 (10.6%) had progressive disease. Stable or
responsive disease was associated with improved median OS of 44 months, compared
with 21 months for those with progressive disease (p = 0.011). CONCLUSIONS: In
selected patients, long-term survival can be obtained. Mucinous histology,
absence of signet ring cells, negative peritoneal cytology, PCI <= 20, and
response/stable disease after neoadjuvant chemotherapy are important selection
criteria for CRS and HIPEC.
PMID- 28695395
TI - A meta-analysis of atosiban supplementation among patients undergoing assisted
reproduction.
AB - OBJECTIVES: Evidence for the efficacy of atosiban in improving pregnancy outcomes
among patients undergoing assisted reproductive technology (ART) remains
inconsistent. METHODS: The PubMed, EMBASE, and CNKI databases were searched using
keywords such as 'atosiban', 'infertility', and 'ART'. Studies that explored the
efficacy of atosiban in the field of ART for patients with embryo transfer (ET)
were included if they evaluated pregnancy outcomes. Combing using subgroups and
sensitivity analysis were conducted, and risk ratios (RRs), and 95% confidence
intervals (CIs) were calculated. RESULTS: Six studies were included. Atosiban
treatment could improve pregnancy outcomes for all patients undergoing ET,
especially for the subgroups of patients with repeated implantation failure (RIF)
(implantation rate: RR = 1.806, 95% CI = 1.473-2.215; clinical pregnancy rate: RR
= 1.725, 95% CI = 1.394-2.135; live birth rate: RR = 2.141, 95% CI = 1.494
3.068), as shown by the comparison with placebo or no-treatment groups. However,
no statistical significance was detected in subgroups of patients undergoing
their first or second ET cycle. In addition, no significant differences were
observed in positive pregnancy tests, miscarriage rates, multiple pregnancy
rates, or ectopic pregnancy rates. CONCLUSIONS: Supplementation with atosiban has
a positive effect on ART and embryo transfer procedure, especially for women
undergoing their third or more ET cycle.
PMID- 28695396
TI - Active smoking and survival following breast cancer among African American and
non-African American women in the Carolina Breast Cancer Study.
AB - PURPOSE: To examine racial differences in smoking rates at the time of breast
cancer diagnosis and subsequent survival among African American and non-African
American women in the Carolina Breast Cancer Study (Phases I/II), a large
population-based North Carolina study. METHODS: We interviewed 788 African
American and 1,020 Caucasian/non-African American women diagnosed with invasive
breast cancer from 1993 to 2000, to assess smoking history. After a median follow
up of 13.56 years, we identified 717 deaths using the National Death Index; 427
were breast cancer-related. We used Cox regression to examine associations
between self-reported measures of smoking and breast cancer-specific survival
within 5 years and up to 18 years after diagnosis conditional on 5-year survival.
We examined race and estrogen receptor status as potential modifiers. RESULTS:
Current (vs never) smoking was not associated with 5-year survival; however, risk
of 13 year conditional breast cancer-specific mortality was elevated among women
who were current smokers at diagnosis (HR 1.54, 95% CI 1.06-2.25), compared to
never smokers. Although smoking rates were similar among African American (22.0%)
and non-African American (22.1%) women, risk of breast cancer-specific mortality
was elevated among African American (HR 1.69, 95% CI 1.00-2.85), but only weakly
elevated among non-African American (HR 1.22, 95% CI 0.70-2.14) current (vs.
never) smokers (P Interaction = 0.30). Risk of breast cancer-specific mortality
was also elevated among current (vs never) smokers diagnosed with ER- (HR 2.58,
95% CI 1.35-4.93), but not ER+ (HR 1.11, 95% CI 0.69-1.78) tumors (P Interaction
= 0.17). CONCLUSIONS: Smoking may negatively impact long-term survival following
breast cancer. Racial differences in long-term survival, as related to smoking,
may be driven by ER status, rather than by differences in smoking patterns.
PMID- 28695397
TI - Effect of ninjin'yoeito and ginseng extracts on oxaliplatin-induced neuropathies
in mice.
AB - Oxaliplatin (L-OHP) is a platinum-based anticancer agent used to treat various
types of cancer. It frequently causes acute and chronic peripheral neuropathies,
such as cold allodynia and mechanical hyperalgesia. Ninjin'yoeito (NYT) is a
formula used in traditional Japanese Kampo medicine to improve recovery from
diseases and other medical disorders. We previously reported that treatment with
a boiling-water extract of NYT prevented L-OHP-induced damage to neurite-like
outgrowths from differentiated PC12 cells. The objectives of the present study
were to evaluate the in vivo effects of NYT on L-OHP-induced neuropathic pain in
mice and identify the active ingredients in NYT. Treatment with NYT extract
significantly ameliorated both cold allodynia and mechanical hyperalgesia induced
by L-OHP. While L-OHP treatment suppressed neurite outgrowths from primary dorsal
root ganglion cells in vitro, NYT extract blocked this suppression in a
concentration-dependent manner. Among the herbal components of NYT, the extract
of ginseng (Panax ginseng roots) showed a protective effect against neurite
damage induced by L-OHP, and one of its active ingredients was identified as
ginsenoside Rg3. Ginseng extract partially relieved L-OHP-induced neuropathic
pain in mice. Our results suggest that NYT could be an attractive agent for
treating L-OHP-induced neuropathic pain, and that the active ingredient of NYT
may be ginseng.
PMID- 28695398
TI - Variable slice thickness (VAST) EPI for the reduction of susceptibility artifacts
in whole-brain GE-EPI at 7 Tesla.
AB - OBJECTIVE: A new technique for 2D gradient-recalled echo echo-planar imaging (GE
EPI) termed 'variable slice thickness' (VAST) is proposed, which reduces signal
losses caused by through-slice susceptibility artifacts, while keeping the volume
repetition time (TR) manageable. The slice thickness is varied across the brain,
with thinner slices being used in the inferior brain regions where signal voids
are most severe. MATERIALS AND METHODS: Various axial slice thickness schemes
with identical whole-brain coverage were compared to regular EPI, which may
either suffer from unfeasibly long TR if appropriately thin slices are used
throughout, or signal loss if no counter-measures are taken. Evaluation is based
on time-course signal-to-noise (tSNR) maps from resting state data and a
statistical group-level region of interest (ROI) analysis on breath-hold fMRI
measurements. RESULTS: The inferior brain region signal voids with static B0
inhomogeneities could be markedly reduced with VAST GE-EPI in contrast to regular
GE-EPI. ROI-averaged event-related signal changes showed 48% increase in VAST
compared to GE-EPI with regular "thick" slices. tSNR measurements proved the
comparable signal robustness of VAST in comparison to regular GE-EPI with thin
slices. CONCLUSION: A novel acquisition strategy for functional 2D GE-EPI at
ultrahigh magnetic field is presented to reduce susceptibility-induced signal
voids and keep TR sufficiently short for whole-brain coverage.
PMID- 28695399
TI - The long-term effects of mandibular advancement splint on cardiovascular fitness
and psychomotor performance in patients with mild to moderate obstructive sleep
apnea: a prospective study.
AB - BACKGROUND: Obstructive sleep apnea (OSA) manifests as a reduction or complete
cessation of airflow despite an ongoing inspiratory effort, leading to hypoxemia
and hypercapnia. The inability to maintain normal breathing reduces the oxygen
saturation in blood leading to a cycle of various systemic implications. Hence, a
prospective single arm study was planned to evaluate the long-term (2 years)
effect of oral appliance on cardiovascular fitness and psychomotor performance in
patients with mild to moderate obstructive sleep apnea. METHODS: Thirty dentulous
OSA patients (25 males; 5 females; age 41 +/- 4 years; BMI 22 +/- 5; AHI 5-30)
were included in the study. All the patients were assessed for systolic blood
pressure (SBP), diastolic blood pressure (DBP), apnea/hypopnea index (AHI), lipid
peroxidation, and psychomotor vigilance test at baseline, 6 months, 1 year, and 2
years after wearing mandibular advancement splint (MAS). RESULTS: A significant
reduction in AHI, blood pressure, and lipid peroxidation was observed following
MAS use. Psychomotor vigilance test showed marked improvement in response time
with almost 0 count of lapses after 2 years of MAS use. CONCLUSIONS: The present
study suggested that MAS can be helpful in improving cardiovascular fitness and
cognitive response in patients with mild to moderate OSA.
PMID- 28695400
TI - Role of Collecting Duct Renin in the Pathogenesis of Hypertension.
AB - The presence of renin production by the principal cells of the collecting duct
has opened new perspectives for the regulation of intrarenal angiotensin II (Ang
II). Angiotensinogen (AGT) and angiotensin-converting enzyme (ACE) are present in
the tubular fluid coming from the proximal tubule and collecting duct. All the
components needed for Ang II formation are present along the nephron, and much is
known about the mechanisms regulating renin in juxtaglomerular cells (JG);
however, those in the collecting duct remain unclear. Ang II suppresses renin via
protein kinase C (PKC) and calcium (Ca2+) in JG cells, but in the principal
cells, Ang II increases renin synthesis and release through a pathophysiological
mechanism that increases further intratubular Ang II de novo formation to enhance
distal Na + reabsorption. Transgenic mice overexpressing renin in the collecting
duct demonstrate the role of collecting duct renin in the development of
hypertension. The story became even more interesting after the discovery of a
specific receptor for renin and prorenin: the prorenin receptor ((P)RR), which
enhances renin activity and fully activates prorenin. The interactions between
(P)RR and prorenin/renin may further increase intratubular Ang II levels. In
addition to Ang II, other mechanisms have been described in the regulation of
renin in the collecting duct, including vasopressin (AVP), bradykinin (BK), and
prostaglandins. Current active investigations are aimed at elucidating the
mechanisms regulating renin in the distal nephron segments and understand its
role in the pathogenesis of hypertension.
PMID- 28695401
TI - Item Response Theory as an Efficient Tool to Describe a Heterogeneous Clinical
Rating Scale in De Novo Idiopathic Parkinson's Disease Patients.
AB - PURPOSE: This manuscript aims to precisely describe the natural disease
progression of Parkinson's disease (PD) patients and evaluate approaches to
increase the drug effect detection power. METHODS: An item response theory (IRT)
longitudinal model was built to describe the natural disease progression of 423
de novo PD patients followed during 48 months while taking into account the
heterogeneous nature of the MDS-UPDRS. Clinical trial simulations were then used
to compare drug effect detection power from IRT and sum of item scores based
analysis under different analysis endpoints and drug effects. RESULTS: The IRT
longitudinal model accurately describes the evolution of patients with and
without PD medications while estimating different progression rates for the
subscales. When comparing analysis methods, the IRT-based one consistently
provided the highest power. CONCLUSION: IRT is a powerful tool which enables to
capture the heterogeneous nature of the MDS-UPDRS.
PMID- 28695402
TI - Wanted: a Transdisciplinary Knowledge Domain for Urban Health.
AB - The current disconnection between access to increasing amounts of data about
urbanization, health, and other global changes and the conflicting meanings and
values of that data has created uncertainty and reduced the ability of people to
act upon available information which they do not necessarily understand. We see a
disconnection between increasing data availability and data processing capability
and capacity. In response to this disconnection, modeling has been attributed an
important role in international and national research programs in order to
predict the future based on past and recent trends. Predictive models are often
data heavy and founded on assumptions which are difficult to verify, especially
regarding urban health issues in specific contexts. Producing large volumes of
data warrants debate about what data are prerequisites for better understanding
human health in changing urban environments. Another concern is how data and
information can be used to apply knowledge. Making sense of empirical knowledge
requires a new transdisciplinary knowledge domain created by a commitment to
convergence between researchers in multiple academic disciplines and other actors
and institutions in cities. Disciplinary-based researchers are no longer the sole
producers of empirical knowledge. Today, diverse kinds of knowledge are becoming
an emergent product of multiple societal stakeholders acting collectively to
address challenges that impact on their habitat, their livelihood, and their
health. Insights from complexity science also require a fundamental rethinking of
the role and responsibility of human agency while admitting rather than denying
complexity and radical uncertainty.
PMID- 28695403
TI - Hybrid coagulation-UF processes for spent filter backwash water treatment: a
comparison studies for PAFCl and FeCl3 as a pre-treatment.
AB - In this study, the reclamation of clean water from spent filter backwash water
(SFBW) was investigated through pilot-scale experiments. The pilot plant
consisted of pre-sedimentation, coagulation, flocculation, clarification, and
ultrafiltration (UF). Two coagulants of PAFCl and FeCl3 were investigated with
respect to their performance on treated SFBW quality and UF membrane fouling. At
the optimum dose of PAFCl and FeCl3 turbidity removal of 99.6 and 99.4% was
attained, respectively. PAFCl resulted in an optimum UV254, TOC, and DOC removal
of 80, 83.6, and 72.7%, respectively, and FeCl3 caused the removal of those
parameters by 76.7, 80.9, and 65.9%, respectively. PAFCl removed hydrophilic and
transphilic constituent better than FeCl3, but FeCl3 had, to some extent, higher
affinities to a hydrophobic fraction. It was concluded that PAFCl showed a better
coagulation performance in most cases and caused a lower membrane fouling rate
compared to FeCl3. Finally, the treated SFBW with both coagulant-UF systems met
the drinking water standards.
PMID- 28695404
TI - Responsible growth of nuclear cardiology in Spain.
PMID- 28695405
TI - What can be and what cannot be accomplished with PET to detect and characterize
atherosclerotic plaques.
PMID- 28695406
TI - Quantification of intramyocardial blood volume with 99mTc-RBC SPECT-CT imaging: A
preclinical study.
AB - BACKGROUND: Currently, there is no established non-invasive imaging approach to
directly evaluate myocardial microcirculatory function in order to diagnose
microvascular disease independent of co-existing epicardial disease. In this
work, we developed a methodological framework for quantification of
intramyocardial blood volume (IMBV) as a novel index of microcirculatory function
with SPECT/CT imaging of 99mTc-labeled red blood cells (RBCs). METHODS: Dual
gated myocardial SPECT/CT equilibrium imaging of 99mTc-RBCs was performed on
twelve canines under resting conditions. Five correction schemes were studied:
cardiac gating with no other corrections (CG), CG with attenuation correction (CG
+ AC), CG + AC with scatter correction (CG + AC + SC), dual cardiorespiratory
gating with AC + SC (DG + AC + SC), and DG + AC + SC with partial volume
correction (DG + AC + SC + PVC). Quantification of IMBV using each approach was
evaluated in comparison to those obtained from all corrections. The in vivo SPECT
estimates of IMBV values were validated against those obtained from ex vivo
microCT imaging of the casted hearts. RESULTS: The estimated IMBV with all
corrections was 0.15 +/- 0.03 for the end-diastolic phase and 0.11 +/- 0.03 for
the end-systolic phase. The cycle-dependent change in IMBV (DeltaIMBV) with all
corrections was 23.9 +/- 8.6%. Schemes that applied no correction or partial
correction resulted in significant over-estimation of IMBV and significant under
underestimation of DeltaIMBV. Estimates of IMBV and DeltaIMBV using all
corrections were consistent with values reported in the literature using invasive
techniques. In vivo SPECT estimates of IMBV strongly correlated (R2 >= 0.70) with
ex vivo measures for the various correction schemes, while the fully corrected
scheme yielded the smallest bias. CONCLUSIONS: Non-invasive quantification of
IMBV is feasible using 99mTc-RBCs SPECT/CT imaging, however, requires full
compensation of physical degradation factors.
PMID- 28695407
TI - Nuclear cardiology in China: 2017.
AB - This paper provides the current state of nuclear cardiology in China and
contrasts it with the state of nuclear cardiology in the United States (US). The
West China Hospital and New York-Presbyterian Hospital (NYPH) were used as
representative hospitals to contrast nuclear cardiology in China and the US,
respectively. In 2015, there were 101 medical cyclotrons, 774 SPECT or SPECT/CT,
240 PET/CT, and 6 PET/MR cameras in China. Most (~90%) of the nuclear cardiology
studies are gated SPECT myocardial perfusion imaging (MPI), and ~10% are other
types of studies including MUGA, PET/CT MPI, and viability studies. There are
differences in nuclear cardiology between the West China Hospital and NYPH and
these include those in cardiac stress tests, SPECT/CT acquisition protocols,
PET/CT blood flow and viability studies, reimbursement, and fellowship training.
In this paper, we aim to present status of nuclear cardiology in China and
provide potential solutions.
PMID- 28695408
TI - A gyrB oligonucleotide microarray for the specific detection of pathogenic
Legionella and three Legionella pneumophila subsp.
AB - Among the 50 species and 70 serogroups of Legionella identified, Legionella
pneumophila, comprising three subsp. (subsp. pneumophila, subsp. fraseri, and
subsp. pasculleii), is recognized as the major cause of epidemic legionellosis.
Rapid and reliable assays to identify pathogenic Legionella spp., and the three
L. pneumophila subsp. in particular, are in great demand. In this study, we
analyzed the gyrB genes of eleven Legionella spp. and subsp., comprising L.
anisa, L. bozemanii, L. dumoffii, L. feeleii, L. gormanii, L. longbeachae, L.
micdadei, L. waltersii, L. pneumophila subsp. pneumophila, L. pneumophila subsp.
fraseri, and L. pneumophila subsp. pasculleii. We developed a rapid
oligonucleotide microarray detection technique to identify accurately these
common pathogenic Legionella spp. and L. pneumophila subsp. To detect multiple
Legionella species with high specificity, 31 reproducible probes were designed in
the array. Sixty-one strains were analyzed in total, including 37 target
pathogens and 24 non-target bacterial species used to validate the microarray.
The sensitivity of the detection was 1.0 ng using genomic DNA of three Legionella
spp., L. anisa, L. dumoffii, and L. waltersii, or 13 CFU/100 mL using the
cultured L. pneumophila subsp. pneumophila. Eight isolated strains were tested
using the microarray with 100% accuracy. The data indicated that the technique is
an efficient method to diagnose and detect Legionella spp. and subsp. in basic
microbiology, clinical diagnosis, epidemiological surveillance, and food safety
applications. In addition, a phylogenetic study based on the gyrB gene revealed
the genetic relationship among the different Legionella spp. and subsp.
PMID- 28695409
TI - Selection and validation of reference genes for RT-qPCR indicates that juice of
sugarcane varieties modulate the expression of C metabolism genes in the
endophytic diazotrophic Herbaspirillum rubrisubalbicans strain HCC103.
AB - Quantitative reverse transcription PCR (RT-qPCR) is an important tool for
evaluating gene expression. However, this technique requires that specific
internal normalizing genes be identified for different experimental conditions.
To date, no internal normalizing genes are available for validation of data
analyses for Herbaspirillum rubrisubalbicans strain HCC103, an endophyte that is
part of the sugarcane consortium inoculant. This work seeks to identify and
evaluate suitable reference genes for gene expression studies in HCC103 grown
until middle log phase in sugarcane juice obtained from four sugarcane varieties
or media with three different carbon sources. The mRNA levels of five candidate
genes (rpoA, gyrA, dnaG, recA and gmK) and seven target genes involved in carbon
metabolism (acnA, fbp, galE, suhB, wcaA, ORF_0127.0101 and _0127.0123) were
quantified by RT-qPCR. Analysis of expression stability of these genes was
carried out using geNorm and Normfinder software. The results indicated that the
HCC103 dnaG and gyrA genes are the most stable and showed adequate relative
expression level changes among the different sugarcane juices. The highest
expression level was seen for ORF_0127.0101, which encodes a sugar transporter,
in juice from sugarcane variety RB867515 and glucose as the carbon source. The
suhB gene, encoding SuhB inositol monophosphatase, had a higher relative
expression level on 0.5% glucose, 100% sugarcane juice from variety RB867515 and
0.5% aconitate. Together the results suggest that dnaG and gyrA genes are
suitable as reference genes for RT-qPCR analysis of strain HCC103 and that juice
from different sugarcane varieties modulates the expression of key genes involved
in carbon metabolism.
PMID- 28695410
TI - Microscale Gaseous Slip Flow in the Insect Trachea and Tracheoles.
AB - An analytical investigation into compressible gas flow with slight rarefactions
through the insect trachea and tracheoles during the closed spiracle phase is
undertaken, and a complete set of asymptotic analytical solutions is presented.
We first obtain estimates of the Reynolds and Mach numbers at the channel
terminal ends where the tracheoles directly deliver respiratory gases to the
cells, by comparing the magnitude of the different forces in the compressible gas
flow. The 2D Navier-Stokes equations with a slip boundary condition are used to
investigate compressibility and rarefied effects in the trachea and tracheoles.
Expressions for the velocity components, pressure gradients and net flow inside
the trachea are then presented. Numerical simulations of the tracheal
compressible flow are performed to validate the analytical results from this
study. This work extends previous work of Arkilic et al. (J Microelectromech Syst
6(2):167-178, 1997) on compressible flows through a microchannel. Novel devices
for microfluidic compressible flow transport may be invented from results
obtained in this study.
PMID- 28695412
TI - [Basis for the treatment of eczematous diseases in otorhinolaryngology].
AB - According to Coombs and Gell, cell-mediated immune responses belong to type IV
reactions and are borne mainly by T lymphocytes. The eliciting allergens are
usually so-called haptens. Haptens are substances which develop to whole antigens
only by binding to protein carriers. In otorhinolaryngology, delayed allergic
hypersensitivities are apparent mainly as contact eczemata. Facial dermatitis,
auricle and ear canal eczema as well as perioral eczema belong to the most common
forms of contact dermatitis in ENT patients. The patient's medical history and
morphology of the eczema give a strong indication for a proper diagnosis.
Verification is carried out by patch test according to the Arbeitsgemeinschaft
der Wissenschaftlichen Medizinischen Fachgesellschaften (AWMF, The Association of
the Scientific Medical Societies in Germany) guidelines. Hereby the most
widespread contact allergens are tested in a so-called "standard block", which
can be reduced to an individualized allergen spectrum, based on medical history.
For therapy, allergen avoidance is the most important measure which should also
be applied prophylactically. Moreover, antiinflammatory treatment of the contact
eczema is carried out with tapering topical corticosteroids. Depending on the
patient's age, location and severity of the contact eczema, newer class II or III
preparations should be chosen. Skin care preparations are helpful to reduce
corticosteroid consumption and are indicated additionally after the acute phase
treatment. An important differential diagnosis of contact eczema is atopic
dermatitis. Whilst contact dermatitis experiences healing by avoiding the
triggering noxious agent, genetically determined atopic dermatitis shows a
chronic, recurrent course. In addition to topical corticosteroids, calcineurin
inhibitors have been approved for treatment of atopic eczema. In all eczema
diseases, regular skin care is a necessary measure which contributes mainly to
barrier repair.
PMID- 28695411
TI - Protective effects of curcumin against rotenone-induced rat model of Parkinson's
disease: in vivo electrophysiological and behavioral study.
AB - Curcumin is a naturally occurring phenolic yellow chemical isolated from the
rhizomes of the plant Curcuma longa (turmeric), and is a major component of the
spice turmeric. Curcumin has protective effects against rotenone-induced neural
damage in Parkinson's disease (PD). The present study aims at providing new
evidence for the validity of the rotenone rat model of PD by examining whether
neuronal activity in the hippocampus is altered. Male albino rats were treated
with rotenone injections (2.5 mg/ml intraperitoneally) for 21 days. We examined
the effects of curcumin (200 mg/kg) on behavior and electrophysiology in a rat
model of PD induced by rotenone. Motor activity was assessed by cylinder test.
The electrical activity of neurons was measured in hippocampus. Rotenone causes
significant reduction of neuronal activity. The results show that curcumin can
improve the motor impairments and electrophysiological parameters and may be
beneficial in the treatment of PD.
PMID- 28695413
TI - [Process, disturbances and improvements of wound healing].
AB - Skin damage induces the wound healing process which leads to primary or secondary
healing in three sequential, partially overlapping phases, due to interaction
among different cells and secretion of pro- and anti-inflammatory mediators. The
subtle equilibrium among repair and breakdown can be disturbed by different local
and systemic factors causing impairment or even stagnancy of a phase with the
effect of chronic wounds or deficient healing. Various surgical and nonsurgical
instruments can be used to promote disturbed towards physiologic healing and
restore the integrity of the organism's protective layer.
PMID- 28695414
TI - Erratum to: DNA damage response and hematological malignancy.
PMID- 28695415
TI - The Real-Life Effectiveness and Care Patterns of Diabetes Management Study for
Balkan Region (Slovenia, Croatia, Serbia, Bulgaria): A Multicenter,
Observational, Cross-Sectional Study.
AB - INTRODUCTION: Recent large randomized controlled trials highlighted the clinical
significance of hypoglycemic episodes in the treatment of diabetes. The present
survey was conducted to provide information from real-life practice on the
incidence of hypoglycemia in type 2 diabetic patients treated with sulfonylureas.
METHODS: This multicenter, observational, cross-sectional study collected data on
incidence of side effects of sulfonylurea-based therapy in type 2 diabetic
patients in four countries of the Balkan region (Slovenia, Croatia, Serbia,
Bulgaria) from October 2014 to June 2015. RESULTS: Of the 608 who participated in
the study, 573 patients (mean age 67.2 years, mean body mass index 29.9 kg/m2)
met the inclusion/exclusion criteria. More than 90% of the patients were treated
with the newer generation sulfonylureas-gliclazide or glimepiride-either as
monotherapy or as dual therapy in combination with metformin. In total, 210
patients (36.6%) reported hypoglycemic episode(s) in the last 6 months. Mild
episodes were reported by 132 patients (62.8%), moderate by 66 (31.2%), severe by
8 patients (4.0%), and very severe by 4 patients (2%), respectively. Overall, 171
patients (28.2%) reported body weight increase during the previous year. The mean
reported body weight gain in this group of patients was 4.2 kg (SD 2.7, median
3). Among them, 68.1% gained less than 5 kg, 25.0% gained 5-9 kg, and the rest
gained more than 10 kg. CONCLUSION: Although newer generation sulfonylureas are
generally considered safe in terms of hypoglycemia, our data indicates their use
is associated with substantial risk of hypoglycemia and weight gain. Clinicians
should be mindful of these findings when prescribing SUs and inform patients
about the risk of hypoglycemia. FUNDING: Merck Sharp & Dohme.
PMID- 28695416
TI - Sources of Variability in Physical Activity Among Inactive People with Multiple
Sclerosis.
AB - PURPOSE: Evidence supports that physical activity (PA) improves symptoms of
multiple sclerosis (MS). Although application of principles from Social Cognitive
Theory (SCT) may facilitate positive changes in PA behaviour among people with
multiple sclerosis (pwMS), the constructs often explain limited variance in PA.
This study investigated the extent to which MS symptoms, including fatigue,
depression, and walking limitations combined with the SCT constructs, explained
more variance in PA than SCT constructs alone among pwMS. METHOD: Baseline data,
including objectively assessed PA, exercise self-efficacy, goal setting, outcome
expectations, 6-min walk test, fatigue and depression, from 65 participants of
the Step It Up randomized controlled trial completed in Ireland (2016), were
included. Multiple regression models quantified variance explained in PA and
independent associations of (1) SCT constructs, (2) symptoms and (3) SCT
constructs and symptoms. RESULTS: Model 1 included exercise self-efficacy,
exercise goal setting and multidimensional outcomes expectations for exercise and
explained ~14% of the variance in PA (R 2=0.144, p < 0.05). Model 2 included
walking limitations, fatigue and depression and explained 20% of the variance in
PA (R 2=0.196, p < 0.01). Model 3 combined models 1 and 2 and explained variance
increased to ~29% (R 2=0.288; p<0.01). In Model 3, exercise self-efficacy
(beta=0.30, p < 0.05), walking limitations (beta=0.32, p < 0.01), fatigue (beta =
-0.41, p < 0.01) and depression (beta = 0.34, p < 0.05) were significantly and
independently associated with PA. CONCLUSION: Findings suggest that relevant MS
symptoms improved by PA, including fatigue, depression and walking limitations,
and SCT constructs together explained more variance in PA than SCT constructs
alone, providing support for targeting both SCT constructs and these symptoms in
the multifactorial promotion of PA among pwMS.
PMID- 28695417
TI - A Fiber Tractography Study of Social-Emotional Related Fiber Tracts in Children
and Adolescents with Autism Spectrum Disorder.
AB - The symptoms of autism spectrum disorder (ASD) have been hypothesized to be
caused by changes in brain connectivity. From the clinical perspective, the
"disconnectivity" hypothesis has been used to explain characteristic impairments
in "socio-emotional" function. Therefore, in this study we compared the facial
emotional recognition (FER) feature and the integrity of social-emotional-related
white-matter tracts between children and adolescents with high-functioning ASD
(HFA) and their typically developing (TD) counterparts. The correlation between
the two factors was explored to find out if impairment of the white-matter tracts
is the neural basis of social-emotional disorders. Compared with the TD group,
FER was significantly impaired and the fractional anisotropy value of the right
cingulate fasciculus was increased in the HFA group (P < 0.01). In conclusion,
the FER function of children and adolescents with HFA was impaired and the
microstructure of the cingulate fasciculus had abnormalities.
PMID- 28695418
TI - CSF-Based Analysis for Identification of Potential Serum Biomarkers of Neural
Tube Defects.
AB - The protein composition of cerebrospinal fluid (CSF) in neural tube defects
(NTDs) remains unknown. We investigated the protein composition of CSF from 9
infants with NTDs using isobaric tags for relative and absolute quantitation
(iTRAQ). We identified 568 proteins in the CSF of infants with spina bifida,
which is the most common type of NTD. Among these, 18 proteins were associated
with neural tube closure in the CSF during human embryonic neurulation and 5 were
involved in NTDs. Based on these results, an animal model was further utilized to
investigate early serum biomarkers for NTDs. We found that the myristoylated
alanine-rich C-kinase substrate, Kunitz-type protease inhibitor 2, and
apolipoprotein B-100 protein levels were decreased in both embryos and the sera
of pregnant Sprague-Dawley rats carrying embryos with NTDs. CSF proteins may be
useful in the discovery of potential serum biomarkers for NTDs.
PMID- 28695419
TI - Implementation of minimally invasive percutaneous nephrolithotomy (MIP):
comparison of the initial learning curve with the later on clinical routine in a
tertiary centre.
AB - OBJECTIVE: We report on the comparison of clinical results of the early phase of
implementation of minimally invasive PNL (MIP) in a mentor-based approach with
the later on clinical routine in a tertiary centre. PATIENTS AND METHODS: From
January 2010 until January 2015 MIP was performed in 190 patients. Stone and
patient characteristics were recorded in prospective manner. Perioperative
complications were recorded within the Clavien-Classification. The first 120
consecutive patients undergoing MIP were evaluated and divided into three groups
of 40 patients each. Mentor-based introduction of MIP was done within the first
40 patients (group A). Further patients were treated on routine clinical practice
basis (group B and C). Treatment outcome was compared within the three groups.
RESULTS: The groups did not significantly differ with regard to patient
characteristics, operation time and decline in haemoglobin. In the mentor-based
series mean stone size was 21.7 +/- 12.6 vs. 15.6 +/- 7.9 and 16.1 +/- 8.4 mm in
group B and C (p = 0.033). Primary stone-free rates were 65, 87.5 and 87.5% for
the three groups (p = 0.015). Stone-free rate was higher in smaller and simple
stones. Overall, complication rate was 41.7% including 36.7% Clavien grade I and
II complications. CONCLUSIONS: MIP can be implemented safe and effectively with
mentor-based approach. MIP has a high safety profile, which allows high safety
and efficacy of MIP at the time of implementation.
PMID- 28695420
TI - Bone lesions in yaws - another potential marker of indigenous Australian remains.
PMID- 28695421
TI - Ruptured varicose veins and fatal hemorrhage.
PMID- 28695422
TI - Does Black Socioeconomic Mobility Explain Recent Progress Toward Black-White
Residential Integration?
AB - Studies of racial residential segregation have found that black-white segregation
in U.S. metropolitan areas has declined slowly but steadily since the early
1970s. As of this writing, black-white residential segregation in the United
States is approximately 25 % lower than it was in 1970. To identify the sources
of this decline, we used individual-level, geocoded data from the Panel Study of
Income Dynamics (PSID) to compare the residential attainment of different cohorts
of blacks. We analyzed these data using Blinder-Oaxaca regression decomposition
techniques that partition the decline in residential segregation among cohorts
into the decline resulting from (1) changes in the social and economic
characteristics of blacks and (2) changes in the association between blacks'
social and economic characteristics and the level of residential segregation they
experience. Our findings show that black cohorts entering adulthood prior to the
civil rights movement of the 1960s experienced consistently high levels of
residential segregation at middle age, but that cohorts transitioning to
adulthood during and after this period of racial progress experienced
significantly lower levels of residential segregation. We find that the decline
in black-white residential segregation for these later cohorts reflects both
their greater social and economic attainment and a strengthening of the
association between socioeconomic characteristics and residential segregation.
Educational gains for the post-civil rights era cohorts and improved access to
integrated neighborhoods for high school graduates and college attendees in these
later cohorts were the principal source of improved residential integration over
this period.
PMID- 28695423
TI - Fertility and Life Satisfaction in Rural Ethiopia.
AB - Despite recent strong interest in the link between fertility and subjective well
being, the focus has centered on developed countries. For poorer countries, in
contrast, the relationship remains rather elusive. Using a well-established panel
survey-the Ethiopian Rural Household Survey (ERHS)-we investigate the empirical
relationship between fertility and life satisfaction in rural Ethiopia, the
largest landlocked country in Africa. Consistent with the fertility theories for
developing countries and with the sociodemographic characteristics of rural
Ethiopia, we hypothesize that this relationship varies by gender and across life
stages, being more positive for men and for parents in old age. Indeed, our
results suggest that older men benefit the most in terms of life satisfaction
from having a large number of children, while the recent birth of a child is
detrimental for the subjective well-being of women at reproductive ages. We
address endogeneity issues by using lagged life satisfaction in ordinary least
squares regressions, through fixed-effects estimation and the use of instrumental
variables.
PMID- 28695424
TI - FLT-PET for early response evaluation of colorectal cancer patients with liver
metastases: a prospective study.
AB - BACKGROUND: Fluoro-L-thymidine (FLT) is a positron emission tomography/computed
tomography (PET/CT) tracer which reflects proliferative activity in a cancer
lesion. The main objective of this prospective explorative study was to evaluate
whether FLT-PET can be used for the early evaluation of treatment response in
colorectal cancer patients (CRC) with liver metastases. Patients with metastatic
CRC having at least one measurable (>1 cm) liver metastasis receiving first-line
chemotherapy were included. A FLT-PET/CT scan was performed at baseline and after
the first treatment. The maximum and mean standardised uptake values (SUVmax,
SUVmean) were measured. After three cycles of chemotherapy, treatment response
was assessed by CT scan based on RECIST 1.1. RESULTS: Thirty-nine consecutive
patients were included of which 27 were evaluable. Dropout was mainly due to
disease complications. Nineteen patients (70%) had a partial response, seven
(26%) had stable disease and one (4%) had progressive disease. A total of 23
patients (85%) had a decrease in FLT uptake following the first treatment. The
patient with progressive disease had the highest increase in FLT uptake in
SUVmax. There was no correlation between the response according to RECIST and the
early changes in FLT uptake measured as SUVmax (p = 0.24). CONCLUSIONS: No
correlation was found between early changes in FLT uptake after the first cycle
of treatment and the response evaluated from subsequent CT scans. It seems
unlikely that FLT-PET can be used on its own for the early response evaluation of
metastatic CRC.
PMID- 28695425
TI - Community Health Workers Bring Cost Savings to Patient-Centered Medical Homes.
AB - The Patient-Centered Medical Home (PCMH) model demonstrated that processes of
care can be improved while unnecessary care, such as preventable emergency
department utilization, can be reduced through better care coordination. A
complementary model, the Integrated Primary Care and Community Support (I-PaCS)
model, which integrates community health workers (CHWs) into primary care
settings, functions beyond improved coordination of primary medical care to
include management of the social determinants of health. However, the PCMH model
puts downward pressure on the panel sizes of primary care providers, increasing
the average fixed costs of care at the practice level. While the I-PaCS model
layers an additional cost of the CHWs into the primary care cost structure, that
additional costs is relatively small. The purpose of this study is to simulate
the effects of the PCMH and I-PaCS models over a 3-year period to account for
program initiation to maturity. The costs and cost offsets of the model were
estimated at the clinic practice level. The studies which find the largest cost
savings are for high-risk, paneled patients and therefore do not represent the
effects of the PCMH model on moderate-utilizing patients or practice-level
effects. We modeled a 12.6% decrease in the inpatient hospital, outpatient
hospital and emergency department costs of high and moderate risk patients. The
PCMH is expected to realize a 1.7% annual savings by year three while the I-PaCS
program is expected to a 7.1% savings in the third year. The two models are
complementary, the I-PaCS program enhancing the cost reduction capability of the
PCMH.
PMID- 28695426
TI - Influenza Vaccination Beliefs and Practices in Elderly Primary Care Patients.
AB - The majority of influenza related deaths and hospitalizations occur among
individuals >=65 years, yet the national influenza vaccination rate for this
group is 63% and is lower in the Hispanic population. Previous studies have
described negative predictors of vaccination; however, there is a knowledge gap
of how influenza vaccine-specific beliefs affect vaccination rates. We examined
the relationship between influenza vaccine health beliefs and vaccination
behaviors in a cross sectional sample of 200 primarily Hispanic patients aged
>=65 years in an academic general internal medicine clinic. Participants were
asked about perceptions of influenza vaccine effectiveness and safety. Interview
responses regarding influenza vaccine concerns were evaluated qualitatively with
conventional content analysis. Logistic regression evaluated associations between
beliefs and self-reported vaccination the previous year, adjusted for age,
gender, and language. Of those approached to complete the questionnaire, 88%
participated. Self-reported influenza vaccination rate during the study year was
75%. Only 46.5% endorsed the belief that influenza vaccine is very effective and
47% that it is very safe. Many stated specific concerns about flu vaccine
including that it causes side effects/adverse outcomes, is not effective, vaccine
components are harmful, and vaccination is not necessary. Belief that the flu
shot causes the flu and concern for variability of the flu shot were associated
with reduced odds of vaccination (aOR 0.19, 95% CI [0.05, 0.83] and 0.06 [0.006,
0.63] respectively). The patient-perceived distinction between cold, flu, and
other symptoms warrants further exploration. This information can be used to
develop targeted communication to promote vaccination.
PMID- 28695427
TI - Distracted Pedestrian Behavior on two Urban College Campuses.
AB - Pedestrian injuries injure about 180,000 individuals and kill 6000 each year in
the United States, and pedestrian injury rates have increased each of the last
several years. Distracted pedestrian behavior may play a role in the trend of
increasing risk for pedestrian injury. Using in vivo behavioral coding over the
course of two weeks on two urban college campuses, this study aimed to (1)
understand the type and rate of distractions engaged in by pedestrians on urban
college campuses, and (2) investigate the impact of distraction on street
crossing safety and behavior. A total of 10,543 pedestrians were observed, 90% of
them young adults. Over one-third of those pedestrians were distracted while
actively crossing roadways. Headphones were the most common distraction (19% of
all pedestrians), followed by text-messaging (8%) and talking on the phone (5%).
Women were more likely to text and talk on the phone than men, and men were more
likely to be wearing headphones. Distracted pedestrians were somewhat less likely
to look for traffic when they entered roadways. As handheld device usage
continues to increase, behavioral interventions should be developed and
implemented. Changes to policy concerning distracted pedestrian behavior,
including improvement of the built environment to reduce pedestrian risk, should
be considered in busy pedestrian areas like urban college campuses.
PMID- 28695428
TI - Discussion-Cervico-Mental Angle Suspensory Ligament: The Keystone to Understand
the Cervico-Mental Angle and the Aging Process of the Neck.
AB - This is a commentary and discussion in response to a cadaveric study entitled,
"Cervico-mental angle suspensory ligament: The keystone to understand the cervico
mental angle and the aging process of the neck." While highlighting the cervico
mental angle suspensory ligament has the potential to give rise to new surgical
technique in neck rejuvenation surgery, the authors caution readers of the
study's major limitation. Without well-documented results aligning with aesthetic
ideals or reports of the safety and longevity of the procedure, it seems too
early to consider this ligament the keystone to understand the aging neck. An
actual surgical technique must be described and further clinical studies need to
be performed before this ligament can be included in the armamentarium of neck
rejuvenation surgery. As the goal of surgery should be a natural result that
restores aesthetic ideals of the youthful neck, regardless of the significance
that this ligament will carry, its application should be tailored to the patient
to avoid overly aggressive treatment. Level of evidence V This journal requires
that authors assign a level of evidence to each article. For a full description
of these Evidence-Based Medicine ratings, please refer to the Table of Contents
or the online Instructions to Authors www.springer.com/00266 .
PMID- 28695429
TI - Cryotherapy for Intra- and Perianal High-Grade Squamous Intraepithelial Lesions
in HIV-Positive Men who have Sex with Men.
AB - BACKGROUND: Available treatment options for anal high-grade squamous
intraepithelial lesions (HSIL) in HIV-positive men who have sex with men (MSM)
are limited by low response rates and frequent recurrences. Cryotherapy is an
established therapeutic option for several pre-malignant skin disorders. METHODS:
This retrospective, non-randomized study included HIV-positive MSM who received
intra- and/or perianal HSIL cryotherapy treatment between 30 December 2008 and 23
April 2015. Cryotherapy was applied in sessions 4-6 weeks apart for a maximum of
five sessions. Patients received a follow-up high-resolution anoscopy (HRA) to
assess treatment response. Complete and partial treatment responders were
followed-up after 6 months and then every 6-12 months to investigate recurrent
HSILs. RESULTS: Of 64 patients [median age 48 years; interquartile range (IQR) 42
56] included in the study, six were lost to follow-up. In total, 35 (60%) of 58
patients responded to treatment. Of 64 patients, 31 (48%) reported one or more
side effects, of which anal pain or tenderness and mild blood loss were reported
most frequently. A total of 19 patients who responded to cryotherapy were
adequately followed-up for over 18 months, of whom 13 (68%) had recurrent HSILs.
CONCLUSION: Cryotherapy is capable of clearing HSIL in HIV-positive MSM, and
treatment success rates are comparable with those reported for current treatment
modalities. The treatment is well tolerated, and side effects are relatively
mild. Future studies should therefore compare the efficacy and tolerability of
cryotherapy with those of current treatment modalities in randomized controlled
trials.
PMID- 28695430
TI - Birt-Hogg-Dube Syndrome: A Review of Dermatological Manifestations and Other
Symptoms.
AB - Birt-Hogg-Dube syndrome (BHD) is an autosomal dominant genodermatosis with
malignant potential characterized by cutaneous and extracutaneous stigmata.
Aberrations in the folliculin (FLCN) gene, which is located on chromosome 17,
have been discovered in individuals with this condition. Over 150 unique
mutations have been identified in BHD. The skin lesions associated with this
condition include fibrofolliculomas, trichodiscomas, perifollicular fibromas, and
acrochordons. Extracutaneous features of the syndrome typically include the lung
(spontaneous pneumothorax and cysts) and the kidney (neoplasms). The only
malignancies associated with BHD are renal cancers; however, other tumors have
been observed in individuals with BHD. In this article, the skin lesions
associated with this condition are reviewed, lung and renal manifestations
associated with this syndrome are presented, and malignancies occurring in these
patients are summarized.
PMID- 28695431
TI - The antitumor efficacy of docetaxel is enhanced by encapsulation in novel
amphiphilic polymer cholesterol-coupled tocopheryl polyethylene glycol 1000
succinate micelles.
AB - Tocopheryl polyethylene glycol 1000 succinate (TPGS) is considered a promising
surfactant, but its high critical micelle concentration (CMC) limits its
application. Cholesterol is hydrophobic, can act as a tumor-targeting ligand, and
has strong binding ability with taxoids. Based on this information, we coupled
cholesterol with TPGS to synthesize cholesterol-coupled TPGS (TPGS-CHMC), which
had a lower CMC than pure TPGS. The TPGS-CHMC was used to prepare micelles
loading with docetaxel (DTX) by a self-assembly method. DTX-loaded TPGS-CHMC
micelles were globule-shaped, 13.3 +/- 2.0 nm in size, and had a zeta potential
of -4.66 +/- 0.41 mv. In vitro release studies demonstrated the delayed release
property of the micelles, which also had a relatively high encapsulation
efficiency and drug loading content of 99.2 and 3.20%, respectively. Furthermore,
the micelles were stable in vitro at a dilution of 100-fold. In vivo antitumor
studies showed that the DTX-loaded TPGS-CHMC micelles significantly enhanced the
antitumor activity of DTX in S180 tumor-bearing mice. Interestingly, the blank
TPGS-CHMC micelles also showed antitumor activity. Our results demonstrate that
TPGS-CHMC is a promising system for DTX delivery that may be suitable for other
hydrophobic antitumor drugs.
PMID- 28695432
TI - Gallbladder Polypoid-Lesions: What Are They and How Should They be Treated? A
Single-Center Experience Based on 1446 Cholecystectomy Patients.
AB - BACKGROUND AND AIM: Gallbladder polypoid-lesions (GPs) are commonly seen on
ultrasonography (USG), but several aspects of this problem are ill-defined. This
study aimed to analyze clinic and pathologic characteristics of 1446 USG-detected
GPs, identify predictive factors for cholesterol lesions and malignancy, and
provide comments and recommendations on specific aspects of GPs. METHODS: We
retrospectively analyzed clinic files of 1446 patients who underwent
cholecystectomy for USG-detected GPs between 2008 and 2015 in Gallbladder
Diseases Center, East Hospital of Tongji University. RESULTS: For the 1446
patients, the F: M ratio and the mean age were 1.06: 1 and 45 years, and most of
them were asymptotic (80.3%) and had multiple polyps (62.5%). All the 1446 GPs
were classified into three categories: cholesterol, benign non-cholesterol, and
malignant lesions, with respective proportion of 87.1% (1260), 11.2% (162), and
1.7% (24). Over half of benign non-cholesterol lesions, of which most were
premalignant neoplasm (adenoma), were less than 10 mm. Multiple number and the
presence of lipid abnormalities were significantly more associated with
cholesterol than non-cholesterol lesions, with odd ratios (OR) of 2.9 (P < 0.001)
and 1.6 (P = 0.023), respectively. Age >=50 years, present symptoms, size >=10 mm
and concurrent gallstones were independent predictive factors to discriminate
malignant polyps from premalignant lesions, with ORs of 16.5 (P < 0.001), 6.3 (P
= 0.013), 41.5 (P = 0.014), and 18.0 (P = 0.002), respectively. CONCLUSIONS:
According to our proposed classification, the vast majority of GPs were
cholesterol lesions without malignant potential and associating with metabolic
diseases. We strongly recommend that risk factors of GPs be investigated by
subtypes, and patients with GPs be treated with personalized and differentiated
strategies.
PMID- 28695433
TI - Reconstruction of Bile Duct Injury and Defect with the Round Ligament.
AB - Lateral injury of the bile duct can occur after cholecystectomy, bile duct
dissection, or exploration. If direct repair is not possible, conversion to
bilioenteric anastomosis can be needed with the risk of long-term bile duct
infections and associated complications. We developed a new surgical technique
which consist of reconstructing the bile duct with the round ligament. The
vascularized round ligament is completely mobilized until its origin and used for
lateral reconstruction of the bile duct to cover the defect. T tube was inserted
and removed after few months. Patency of the bile duct was assessed by
cholangiography, the liver function test and magnetic resonance imaging (MRI).
Two patients aged 33 and 59 years old underwent lateral reconstruction of the
bile duct for defects secondary to choledocotomy for stone extraction or during
dissection for Mirizzi syndrome. The defects measured 2 and 3 cm and occupied
half of the bile duct circumference. The postoperative course was marked by low
output biliary fistula resolved spontaneously. In one patient, the T tube was
removed at 3 months after surgery and MRI at 9 months showed strictly normal
aspect of the bile duct with normal liver function test. The second patient is
going very well 2 months after surgery and the T tube is closed. Lateral
reconstruction of the bile duct can be safely achieved with the vascularized
round ligament. We will extend our indications to tubular reconstruction.
PMID- 28695434
TI - The single-nucleotide polymorphism (SNP) of tumor necrosis factor alpha -308G/A
gene is associated with early-onset primary knee osteoarthritis in an Egyptian
female population.
AB - The objective of the present study is to investigate if there is a potential
association between the single-nucleotide polymorphisms (SNPs) of the tumor
necrosis factor alpha gene (TNF-alpha -308G/A, rs1800629) and the susceptibility
to and severity of early-onset knee osteoarthritis in the Egyptian female
population. Genotype distributions and allelic frequencies of TNF-alpha -308G/A
polymorphism were investigated in 210 knee osteoarthritis (OA) patients and 210
age-, sex-, and ethnicity-matched healthy controls (HC). Polymerase chain
reaction-restricted fragment length polymorphism (PCR-RFLP) amplifications were
implemented to determine TNF-alpha -308G/A SNP. Serum and synovial fluid levels
of TNF-alpha, besides ESR and CRP, as laboratory markers for inflammation, were
estimated for all patients and HC. Plain X-ray as well as MRI knee was done for
grading of OA. Disease severity was estimated by Western Ontario and McMaster
University Osteoarthritis scores. Percentages of TNF-alpha-G308A genotypes GG,
AG, and AA were 85.7, 11.9, and 2.4% in OA patients and 54.7, 39.1, and 6.2% in
controls, respectively. The frequencies of the GG genotype and G allele were
significantly higher in subjects with knee OA than in HC (P = 0.04 and P < 0.001,
respectively). Logistic regression analysis showed that the GG genotype and G
allele are independently associated with increased risk for knee OA (odds ratio =
3.13, 95% confidence interval = 1.04-9.39, P = 0.04 for GG genotype, and odds
ratio = 3.81, 95% confidence interval = 2.52-5.76, P = 0.001 for G allele). There
is a close relationship between TNF-alpha-G308A polymorphism and individual
susceptibility to and severity of early-onset knee OA in the Egyptian females.
PMID- 28695435
TI - Evaluation of development of subclinical atherosclerosis in children with
uveitis.
AB - Uveitis is a chronic inflammatory disease. Chronic inflammation has been shown to
have a role in pathogenesis of atherosclerosis. Atherosclerosis is the most
important risk factor of cardiovascular diseases and is shown to start as early
as childhood. In this study, we investigated the presence of subclinical
atherosclerosis in children with uveitis. Seventy five patients who were
diagnosed as having uveitis in ophthalmology and pediatric rheumatology clinics
were included in the study. Patients with hypertension, obesity, dyslipidemia,
diabetes, and with history of early cardiovascular disease were excluded.
Arterial stiffness, carotid-femoral pulse wave velocity (PWV), augmentation index
(AIx), and carotid artery intima-media thickness (cIMT) were measured for each
patient. These measurements were compared with 50 healthy children with similar
age and sex as controls. The mean age of patients in this study was 12.24 +/-
2.69 years, and the mean age of controls was 11.32 +/- 4.52 years. PWV and AIx
values were higher in the patient group (p = 0.04, p = 0.03). cIMT levels were
not different in patient and control groups. When patients were grouped as having
uveitis for more than 5 years or not, patients with longer duration of uveitis
had higher PWV, AIx, and cIMT levels (p values were 0.01, 0.02, and 0.04
respectively). Vascular functions deteriorate first with endothelial damage in
children with uveitis and as disease continues, increase in cIMT is added. We
think that for follow-up of the disease and evaluation of the treatment, non
invasive subclinical atherosclerosis markers should be used along with activation
criteria of primary diseases.
PMID- 28695436
TI - Coherence of Representations Regarding the Child, Resolution of the Child's
Diagnosis and Emotional Availability: A Study of Arab-Israeli Mothers of Children
with ASD.
AB - This study examined the interplay of mothers' coherent representations of their
child (i.e., multidimensional and balanced view); resolution of the child's ASD
diagnosis (i.e., acceptance); and emotional availability to the child in the
unique cultural context of Arab-Israeli families. Participants were 46 mothers
and their 2-8 year old sons. Coherent representations and resolution of the
diagnosis were assessed using narrative measures. Emotional availability (namely,
sensitivity, structuring, and lack of intrusiveness and hostility) was observed
during mother-child play interactions. Results suggested that coherent and
resolved mothers were more emotionally available than incoherent and/or
unresolved mothers. These findings highlight the importance of supporting
mothers' ability to accept the child's diagnosis and see the unique
characteristics of the child beyond his ASD symptoms.
PMID- 28695437
TI - Quantitative Aspects of Communicative Impairment Ascertained in a Large National
Survey of Japanese Children.
AB - The Japanese version of the Children's Communication Checklist-2 (CCC-2) was
rated by caregivers in a large national population sample of 22,871 children aged
3-15 years. The General Communication Composite (GCC) of the CCC-2 exhibited a
distribution with a single-factor structure. The GCC distribution between autism
spectrum disorders (ASD) and language impairment (LI) groups in the general
population fit inside a bell curve with significant overlap with the general
population, and a continuum was evident between groups. No evidence of a natural
cutoff that would differentiate categorically affected from unaffected children
was seen. The Social Interaction Deviance Composite (SIDC) supported the notion
that ASD and LI are on the opposite endpoints of a SIDC continuum of
communication impairment.
PMID- 28695438
TI - Developing Clinically Practicable Biomarkers for Autism Spectrum Disorder.
AB - Despite significant advances in understanding the biological bases of autism
spectrum disorder (ASD), the field remains primarily reliant on observational and
parent report measures of behavior to guide clinical practice, conduct research,
and evaluate intervention outcomes. There is a critical need for objective
measures to more sensitively and validly quantify risk for ASD, ASD
symptomatology, and its change in clinical trials. To maximize public health
impact, such biomarkers must be cost effective and utilize accessible and
scalable technologies. This letter describes concerns specific to the development
of clinically practicable biomarkers for ASD and approaches to optimize
understanding of these biomarkers through development of large-scale consortia
and clinical networks.
PMID- 28695439
TI - Subjective Burden and Depression in Mothers of Children with Autism Spectrum
Disorder in India: Moderating Effect of Social Support.
AB - The quantitative study assessed subjective burden, depression, and the moderating
effect of social support in mothers of children with autism spectrum disorder
(ASD) in India. Seventy mothers were interviewed using a structured interview
schedule, which measured their subjective burden, depression, and social support
from family, friends, and significant others. Data was analyzed using descriptive
statistics and multiple regression analysis with interaction terms. Half of the
mothers in the study reported depression of clinical significance. Higher
subjective burden significantly predicted higher depression. Of the three sources
of support, only medium/high family support had a direct impact on depression and
also moderated the impact of the subjective burden of depression. Implications
for practice and policy are discussed.
PMID- 28695440
TI - An IR Sensor Based Smart System to Approximate Core Body Temperature.
AB - Herein demonstrated experiment studies two methods, namely convection and body
resistance, to approximate human core body temperature. The proposed system is
highly energy efficient that consumes only 165 mW power and runs on 5 VDC source.
The implemented solution employs an IR thermographic sensor of industry grade
along with AT Mega 328 breakout board. Ordinarily, the IR sensor is placed 1.5-30
cm away from human forehead (i.e., non-invasive) and measured the raw data in
terms of skin and ambient temperature which is then converted using appropriate
approximation formula to find out core body temperature. The raw data is plotted,
visualized, and stored instantaneously in a local machine by means of two tools
such as Makerplot, and JAVA-JAR. The test is performed when human object is in
complete rest and after 10 min of walk. Achieved results are compared with the
CoreTemp CM-210 sensor (by Terumo, Japan) which is calculated to be 0.7 degrees
F different from the average value of BCT, obtained by the proposed IR sensor
system. Upon a slight modification, the presented model can be connected with a
remotely placed Internet of Things cloud service, which may be useful to inform
and predict the user's core body temperature through a probabilistic view. It is
also comprehended that such system can be useful as wearable device to be worn on
at the hat attachable way.
PMID- 28695441
TI - Health care cost consequences of using robot technology for hysterectomy: a
register-based study of consecutive patients during 2006-2013.
AB - The objective of this study is to examine the costs attributable to robotic
assisted laparoscopic hysterectomy from a broad healthcare sector perspective in
a register-based longitudinal study. The population in this study were 7670
consecutive women undergoing hysterectomy between January 2006 and August 2013 in
public hospitals in Denmark. The interventions in the study were total and
radical hysterectomy performed robotic-assisted laparoscopic hysterectomy (RALH),
total laparoscopic hysterectomy (TLH), or open abdominal hysterectomy (OAH).
Service use in the healthcare sector was evaluated 1 year before to 1 year after
the surgery. Tariffs of the activity-based remuneration system and the diagnosis
related grouping case-mix system were used for valuation of primary and secondary
care, respectively. Costs attributable to RALH were estimated using a difference
in-difference analytical approach and adjusted using multivariate linear
regression. The main outcome measure was costs attributable to OAH, TLH, and
RALH. For benign conditions RALH generated cost savings of ? 2460 (95% CI 845;
4075) per patient compared to OAH and non-significant cost savings of ? 1045 (95%
CI -200; 2291) when compared with TLH. In cancer patients RALH generated cost
savings of 3445 (95% CI 415; 6474) per patient when compared to OAH and increased
costs of ? 3345 (95% CI 2348; 4342) when compared to TLH. In cancer patients
undergoing radical hysterectomy, RALH generated non-significant extra costs
compared to OAH. Cost consequences were primarily due to differences in the use
of inpatient service. There is a cost argument for using robot technology in
patients with benign disease. In patients with malignant disease, the cost
argument is dependent on comparator.
PMID- 28695443
TI - 3D Experimental and Computational Analysis of Eccentric Mitral Regurgitant Jets
in a Mock Imaging Heart Chamber.
AB - Mitral valve regurgitation (MR) is a disorder of the heart in which the mitral
valve does not close properly. This causes an abnormal leaking of blood backwards
from the left ventricle into the left atrium during the systolic contractions of
the left ventricle. Noninvasive assessment of MR using echocardiography is an
ongoing challenge. In particular, a major problem are eccentric or Coanda
regurgitant jets which hug the walls of the left atrium and appear smaller in the
color Doppler image of regurgitant flow. This manuscript presents a comprehensive
investigation of Coanda regurgitant jets and the associated intracardiac flows by
using a combination of experimental and computational approaches. An anatomically
correct mock heart chamber connected to a pulsatile flow loop is used to generate
the physiologically relevant flow conditions, and the influence of two clinically
relevant parameters (orifice aspect ratio and regurgitant volume) on the onset of
Coanda effect is studied. A two parameter bifurcation diagram showing transition
to Coanda jets is obtained, indicating that: (1) strong wall hugging jets occur
in long and narrow orifices with moderate to large regurgitant volumes, and (2)
short orifices with moderate to large regurgitant volumes produce strong 3D flow
features such as vortex rolls, giving rise to the velocities that are orthogonal
to the 2D plane associated with the apical color Doppler views, making them
"invisible" to the single plane color Doppler assessment of MR. This is the first
work in which the presence of vortex rolls in the left atrium during
regurgitation is reported and identified as one of the reasons for under
estimation of regurgitant volume. The results of this work can be used for better
design of imaging strategies in noninvasive assessment of MR, and for better
understanding of LA remodeling that may be associated with the presence of
maladapted vortex dynamics. This introduces a new concept in clinical imaging,
which emphasizes that the quality and not only the quantity of regurgitant flow
matters in the assessment of severity of mitral valve regurgitation.
PMID- 28695442
TI - Fistula First Initiative: Historical Impact on Vascular Access Practice Patterns
and Influence on Future Vascular Access Care.
AB - The vascular access is the lifeline for the hemodialysis patient. In the United
States, the Fistula First Breakthrough Initiative (FFBI) has been influential in
improving use of arteriovenous fistulas (AVF) in prevalent hemodialysis patients.
Currently, prevalent AVF rates are near the goal of 66% set forth by the original
FFBI. However, central venous catheter (CVC) rates remain very high in the United
States in patients initiating hemodialysis, nearly exceeding 80%. A new direction
of the of the FFBI has focused on strategies to reduce CVC use, and subsequently
the FFBI has now been renamed the "Fistula First-Catheter Last Initiative".
However, an AVF may not be the best vascular access in all hemodialysis patients,
and arteriovenous grafts (AVG) and CVCs may be appropriate and the best access
for a subset of hemodialysis patients. Unfortunately, there still remains very
little emphasis within vascular access initiatives and guidelines directed
towards evaluation of the individual patient context, specifically patients with
poor long-term prognoses and short life expectancies, patients with multiple
comorbidities, patients who are more likely to die than reach end stage renal
disease (ESRD), and patients of elderly age with impaired physical and cognitive
function. Given the complexity of medical and social issues in advanced CKD and
ESRD patients, planning, selection, and placement of the most appropriate
vascular access are ideally managed within a multidisciplinary setting and
requires consideration of several factors including national vascular access
guidelines. Thus, the evolution of the FFBI should underscore the need for
multidisciplinary health teams with a major emphasis placed on "the right access
for the right patient" and improving the patient's overall quality of life.
PMID- 28695444
TI - Severe Fetal Abnormality and Outcomes of Continued Pregnancies: A French
Multicenter Retrospective Study.
AB - Objectives To describe a population choosing to continue with their pregnancy
despite being eligible to receive a medical termination of pregnancy (TOP).
Methods Nine-year retrospective study of data (01/01/2006 to 31/12/2014) from
three French prenatal diagnostic centers describing the perinatal outcomes of
these pregnancies. Pregnancies were classified according to etiology and severity
of its fetal pathology. Several perinatal parameters were described: maternal
characteristics, parental prenatal choices and information on the pregnancy and
neonatal outcomes. These parameters were classified in function of the severity
of fetal pathology according to the classification proposed by Dommergues et al.
(Prenatal Diagnosis 30(6):531-539, 2010) Results Overall, 155 pregnancies were
continued; 140 have been included in our study. Pregnancy outcomes consisted of
four TOPs (2.9%); 20 in utero deaths (14.3%); 110 live births (78.6%) of which
55.4% were still alive at 2 years old as the most recent information; and 6
(4.2%) with unknown outcomes. In 27 cases, perinatal palliative care was
requested (an increase of 37% over 9 years). 36.4% of cases were classified as
having a high mortality risk; 19.3% with a severe handicap risk; 11.4% with a
risk of isolated intellectual disability; and 32.9% with an uncertain prognosis.
The parental decisions to choose perinatal palliative care were significantly
higher within the high mortality risk group as compared to other severity groups
(p < 0.001); this group also had a significantly higher mortality (p < 0.001),
with a survival rate of 26.3%. Conclusion Over the study period, in France, there
was an increase in continued pregnancies, despite a diagnosis of severe fetal
pathology in France. Therefore, it is essential that perinatal professionals are
provided with a palliative care framework and training in their approach for this
population which is heterogeneous in terms of etiology.
PMID- 28695445
TI - Parental and Child Factors Associated with Under-Estimation of Children with
Excess Weight in Spain.
AB - Objective Understanding obesity misperception and associated factors can improve
strategies to increase obesity identification and intervention. We investigate
underestimation of child excess weight with a broader perspective, incorporating
perceptions, views, and psychosocial aspects associated with obesity. Methods
This study used cross-sectional data from the Spanish National Health Survey in
2011-2012 for children aged 2-14 years who are overweight or obese. Percentages
of parental misperceived excess weight were calculated. Crude and adjusted
analyses were performed for both child and parental factors analyzing
associations with underestimation. Results Two-five year olds have the highest
prevalence of misperceived overweight or obesity around 90%. In the 10-14 year
old age group approximately 63% of overweight teens were misperceived as normal
weight and 35.7 and 40% of obese males and females. Child gender did not affect
underestimation, whereas a younger age did. Aspects of child social and mental
health were associated with under-estimation, as was short sleep duration.
Exercise, weekend TV and videogames, and food habits had no effect on
underestimation. Fathers were more likely to misperceive their child's weight
status; however parent's age had no effect. Smokers and parents with excess
weight were less likely to misperceive their child's weight status. Parents being
on a diet also decreased odds of underestimation. Conclusions for practice This
study identifies some characteristics of both parents and children which are
associated with under-estimation of child excess weight. These characteristics
can be used for consideration in primary care, prevention strategies and for
further research.
PMID- 28695446
TI - Intra-catheter endoscopy for various shunting procedures-a retrospective analysis
on surgical practicability, catheter placement, and failure rates.
AB - BACKGROUND: The long-term function of a cerebral shunt is directly influenced by
the placement of the ventricle catheter. In this work, an intra-luminal endoscope
for best possible catheter positioning was used. Practicability, postoperative
imaging, and shunt failure rates were retrospectively evaluated. METHODS: Between
January 2012 and June 2016, an intra-catheter endoscope was applied in 71
procedures. Endoscopic technique was used for catheter placement in first-time
shunting or cerebrospinal fluid reservoir insertion (n = 38), revision surgery in
proximal shunt failure (n = 13), and various intraventricular stenting procedures
(n = 20). Catheter positioning was graded on postoperative imaging using a four
point scale. All patients were regularly followed up (mean, 31.6 months) to
recognize shunt failures. RESULTS: Endoscopic application could be completed as
intended in 68 of 71 procedures. Postoperative imaging could exclude complete
misplacement of all catheters, but optimal positioning was only achieved in 64.7%
(44/68 cases). Four catheters had to be revised due to malfunction (failure rate,
5.8%). Another five catheters had to be removed due to infectious complications
or wound-healing disorders. Direct correlations between catheter complications
and suboptimal catheter positioning were not seen. Slit or distorted ventricles
also did not prove to be a risk factor for the observed complications.
CONCLUSIONS: Versatile application possibilities of the intra-catheter endoscope
reflect the advantages of the technique. Independent of the performed procedure,
unintended positionings or even complete catheter misplacements could be avoided.
However, in more than one-third of all cases, suboptimal catheter placements
became obvious. Interestingly, negative influences on later shunt failures were
not seen.
PMID- 28695447
TI - Regional differences in the incidence of aneurysmal subarachnoid haemorrhage in
Finland.
AB - BACKGROUND: Over the years, the consensus has generally been that Finland is a
country with a significantly high incidence of aneurysmal subarachnoid
haemorrhage (SAH) when compared to the rest of the world, excluding Japan. Most
of the traditionally cited Finnish incidence studies are several decades old and
have clear differences in their methodology and study design. The objective of
this study was to determine the hospital-admitted incidence of aneurysmal SAH at
Tampere University Hospital between 1990 and 2014. We also compared the incidence
to other geographical regions in Finland. METHODS: The material for this study
consists of patients admitted to Tampere University Hospital between 1990 and
2014 with the presentation of aneurysmal SAH. There was a total of 1965 patients
with aneurysmal SAH in our data. RESULTS: The mean hospital-admitted aneurysmal
SAH incidence over the period was 7.41 per 100,000 person-years. The hospital
admitted aneurysmal SAH incidence in the Eastern Finland region was two-thirds
greater than in the Tampere University Hospital region. CONCLUSIONS: We observed
a relatively steady hospital-admitted incidence of aneurysmal SAH (7.41 per
100,000 person-years) in the Tampere University Hospital region. This result is
parallel to a recent study looking into the incidence of aneurysmal SAH for the
whole of Finland. Compared to the Tampere University Hospital region, the
incidence was 64% greater in the Eastern Finland region.
PMID- 28695448
TI - Mitochondrial ATP-Mg/phosphate carriers transport divalent inorganic cations in
complex with ATP.
AB - The ATP-Mg/phosphate carriers (APCs) modulate the intramitochondrial adenine
nucleotide pool size. In this study the concentration-dependent effects of Mg2+
and other divalent cations (Me2+) on the transport of [3H]ATP in liposomes
reconstituted with purified human and Arabidopsis APCs (hAPCs and AtAPCs,
respectively, including some lacking their N-terminal domains) have been
investigated. The transport of Me2+ mediated by these proteins was also measured.
In the presence of a low external concentration of [3H]ATP (12 MUM) and
increasing concentrations of Me2+, Mg2+ stimulated the activity (measured as
initial transport rate of [3H]ATP) of hAPCs and decreased that of AtAPCs; Fe2+
and Zn2+ stimulated markedly hAPCs and moderately AtAPCs; Ca2+ and Mn2+ markedly
AtAPCs and moderately hAPCs; and Cu2+ decreased the activity of both hAPCs and
AtAPCs. All the Me2+-dependent effects correlated well with the amount of ATP-Me
complex present. The transport of [14C]AMP, which has a much lower ability of
complexation than ATP, was not affected by the presence of the Me2+ tested,
except Cu2+. Furthermore, the transport of [3H]ATP catalyzed by the ATP/ADP
carrier, which is known to transport only free ATP and ADP, was inhibited by all
the Me2+ tested in an inverse relationship with the formation of the ATP-Me
complex. Finally, direct measurements of Mg2+, Mn2+, Fe2+, Zn2+ and Cu2+ showed
that they are cotransported with ATP by both hAPCs and AtAPCs. It is likely that
in vivo APCs transport free ATP and ATP-Mg complex to different degrees, and
probably trace amounts of other Me2+ in complex with ATP.
PMID- 28695449
TI - Obstructing pathology of the upper airway in a post-NAP4 world: time to wake up
to its optimal management.
PMID- 28695450
TI - Biofunctionalization of porcine-derived collagen matrix using enamel matrix
derivative and platelet-rich fibrin: influence on mature endothelial cell
characteristics in vitro.
AB - OBJECTIVES: The present study evaluated the effect of an enamel matrix derivative
(EMD) and platelet-rich fibrin (PRF)-modified porcine-derived collagen matrix
(PDCM) on human umbilical vein endothelial cells (HUVEC) in vitro. MATERIALS AND
METHODS: PDCM (mucoderm(r)) was prepared to 6 mm (+/-0.1 mm) diameter discs. PDCM
samples were incubated with either EMD, PRF, or control solutions for 100 min at
4 degrees C before the experiments. Cell-inducing properties of test materials
on HUVEC cells were tested with cell proliferation assays (MTT, PrestoBlue(r)), a
cytotoxicity assay (ToxiLight(r)), a Boyden chamber migration assay, and a cell
attachment assay. Scanning electron microscopy (SEM) imaging was performed to
determine the surface and the architecture of the modified matrices. RESULTS:
Cell proliferation was elevated in the EMD and PRF groups compared with control
(p each <=0.046). PRF modification increased HUVEC migration ability by 8-fold
compared with both control and EMD groups (p each <0.001). Both treatments
significantly promoted the cell attachment of HUVEC to PDCM, as assessed by
direct cell counts on the matrices (p each <0.001). CONCLUSIONS: HUVEC cell
characteristics were overall improved by EMD- and PRF- modified PDCM. Adsorbed
bioactive molecules to the PDCM surface may have contributed to a more preferable
environment to surrounding cells. CLINICAL RELEVANCE: The results may give
evidence that PDCM modification with EMD or PRF, respectively, might be a useful
approach to improve clinical outcomes, to prevent inflammatory reactions and
wound-healing disturbances, and to expand the clinical application area of PDCM.
PMID- 28695452
TI - Chronic hepatitis B: correlation of abnormal features on T2-weighted imaging and
dynamic contrast-enhanced imaging with hepatic histopathology.
AB - OBJECTIVES: To investigate the correlations between abnormal features on liver
magnetic resonance (MR) T2-weighted imaging (T2WI) and dynamic contrast-enhanced
(DCE) imaging and the pathological findings in chronic hepatitis B. MATERIALS AND
METHODS: Sixty-seven patients with chronic hepatitis B and 18 normal controls who
were undergone an abdominal MR imaging were analyzed retrospectively. Patchy
hyperintensities, linear and reticular hyperintensities in liver and periportal
edema on T2WI and abnormal intrahepatic enhancement signals on DCE imaging were
noted. The correlations between the abnormal features detected on hepatic T2WI
and DCE imaging, and the levels of inflammatory activity and fibrosis were
determined. RESULTS: Logistic regression analysis showed increased patchy
hyperintensities (B = 1.869, P = 0.001) on T2WI and patchy enhancement (B =
1.596, P = 0.004) at the arterial phase along with increased inflammatory
activity. However, linear and reticular hyperintensities (B = 2.356, P = 0.000)
on T2WI, and meshwork enhancement (B = 2.191, P = 0.000) at the equilibrium
phase, all correlated with fibrosis. Moreover, periportal edema mainly correlated
with the inflammatory activities (B = 2.635, P = 0.001). CONCLUSIONS: In chronic
hepatitis B patients, patchy hyperintensities on T2WI, periportal edema, and
patchy enhancement at the arterial phase can predict moderate-to-severe
inflammatory activities, whereas intrahepatic linear and reticular
hyperintensities on T2WI, and meshwork enhancement at the equilibrium phase can
predict moderate-to-severe fibrosis.
PMID- 28695451
TI - The endoscopic findings of the upper gastrointestinal tract in patients with
Crohn's disease.
AB - Crohn's disease (CD) is a type of chronic inflammatory bowel disease (IBD)
associated with ulceration, and the main foci of the inflammation in CD patients
are typically the terminal ileum and colon. However, in the upper
gastrointestinal tract (GIT), including the esophagus, stomach and duodenum,
inflammatory lesions are also detected as well, with a relatively high frequency
(30-75%). Recent advances in imaging modalities, including endoscopy, have aided
in the diagnosis of CD. Various lesions, including aphtha, erosion, ulcers,
bamboo-joint-like appearance and notch-like appearance, are detected in the upper
GI of CD patients. Of these lesions, the bamboo-joint-like appearance in the
gastric cardiac region and notch-like appearance in the second portion of the
duodenum are highly specific for CD, regardless of the disease activity at other
sites. These two findings, particularly a bamboo-joint-like appearance, have
therefore been considered as potential biomarkers for CD. Although proton pump
inhibitors (PPIs) are administered as an initial treatment for upper GIT lesions
of CD, the efficacy of this treatment remains controversial. The administration
of mesalazine, steroids, immunosuppressant and biologic agents is expected to be
effective for treating such lesions.
PMID- 28695453
TI - Renal epithelioid angiomyolipoma: MRI findings.
AB - PURPOSE: To retrospectively analyze the MR imaging presentation of renal
epithelioid angiomyolipoma (EAML). METHODS: Retrospective analysis revealed 12
subjects with histologically proven renal EAML who underwent preoperative MRI at
our institution between January 2009 and June 2016. Two radiologists reviewed the
images in consensus, describing MR imaging features including size, location,
growth pattern, signal intensity of tumor, and dynamic enhancement pattern.
RESULTS: Nine women and three men were included. The average maximum tumor
diameter was 7.1 cm. Exophytic growth was present in 9/12 cases, mesophytic
growth in 2/12, and endophytic growth in 1/12. On T1-weighted images, 2/12
displayed homogeneous isointensity, 1/12 homogeneous hyperintensity, 5/12
heterogeneous hypointensity, and 4/12 heterogeneous hyperintensity. Macroscopic
fat was detected in 5/12 cases and microscopic fat in 6/12 cases. On T2-weighted
images, 5/12 showed heterogeneous hypointensity, 4/12 heterogeneous
hyperintensity, and 3/12 homogeneous hypointensity. On dynamic contrast-enhanced
MR images, 7/12 showed a slow washout enhancement pattern, 2/12 a rapid washout
pattern, 2/12 progressive enhancement, and 1/12 persistent enhancement. Imaging
findings were suggestive of hemorrhage (50%), necrosis (25%), or cystic change
(50%) within the tumors. Enlarged vessels were detected in 5/12 cases. One tumor
extended into the renal sinus. No metastases were found on the preoperative MR
imaging. CONCLUSION: Although MRI appearances of renal EAML were various, some
MRI characteristics may contribute to suggest the possibility of renal EAML.
PMID- 28695454
TI - Erratum to: Analysis of E-cigarette use in the 2014 Eurobarometer survey: calling
out deficiencies in epidemiology methods.
PMID- 28695455
TI - PCSK9 inhibitors for treating dyslipidemia in patients at different
cardiovascular risk: a systematic review and a meta-analysis.
AB - Statin-induced lowering of low-density lipoprotein cholesterol (LDL-C) reduces
cardiovascular morbidity and mortality, but many patients do not adequately
reduce their LDL-C levels. Monoclonal antibodies targeting PCKS9 are currently in
the advanced phase of development. We aimed to investigate the efficacy and
safety of PCSK9 inhibitors in patients at different cardiovascular risk in a
systematic review. Studies were searched on MEDLINE and EMBASE until January
2016. Differences in the outcomes among groups were expressed as mean
differences, or pooled odds ratio (OR) and corresponding 95% confidence interval
(CI), which were calculated using a fixed-effects and a random-effects model.
Statistical heterogeneity was evaluated using the I 2 statistic. 22 RCTs and 8833
patients were included. Six studies were performed in patients affected by
homozygous or heterozygous familial hypercholesterolemia, or with increased
cardiovascular risk, two in patients with statin intolerance, three in statin
naive patients, and 10 in patients unable to achieve LDL-C target with statin
therapy. PCSK9 inhibitors were associated with a statistically significant
reduction of LDL-C (mean = -48.8%; 95% CI -54.1, -43.4; I 2 = 94%) compared to
control groups, and with a statistically significant reduction in death for any
cause (OR = 0.34; 95% CI 0.17, 0.69; I 2 = 0) and a favorable trend for
cardiovascular events (OR = 0.79; 95% CI 0.61, 1.02; I 2 = 0%). PCSK9 inhibitors
reduce LDL-C concentration in every group explored. A significant reduction in
death by all cause was observed in the PCSK9 inhibitors groups, compared with
control groups, even in the short time frame studied.
PMID- 28695456
TI - Endoscopic Abscess Septotomy for Management of Sleeve Gastrectomy Leak.
PMID- 28695457
TI - The Role of Laboratory Testing in Differentiating Type 1 Diabetes from Type 2
Diabetes in Patients Undergoing Bariatric Surgery.
AB - BACKGROUND: It may be difficult to distinguish between adults with type 1
diabetes and type 2 diabetes by clinical assessment. In patients undergoing
bariatric surgery, it is critical to correctly classify diabetes subtype to
prevent adverse perioperative outcomes including diabetic ketoacidosis. This
study aimed to determine whether testing for C-peptide and islet cell antibodies
during preoperative evaluation for bariatric surgery could improve the
classification of type 1 versus type 2 diabetes compared to clinical assessment
alone. METHODS: This is a retrospective analysis of the Improving Diabetes
through Lifestyle and Surgery trial, which randomized patients with clinically
diagnosed type 2 diabetes and BMI 30-40 kg/m2 to medical weight loss or bariatric
surgery; one participant was discovered to have type 1 diabetes after
experiencing postoperative diabetic ketoacidosis. Using blood samples collected
prior to study interventions, we measured islet cell antibodies and fasting/meal
stimulated C-peptide in all participants. RESULTS: The participant with type 1
diabetes was similar to the 11 participants with type 2 diabetes in age at
diagnosis, adiposity, and glycemic control but had the lowest C-peptide levels.
Among insulin-treated participants, fasting and stimulated C-peptide correlated
strongly with the C-peptide area-under-the-curve on mixed meal tolerance testing
(R = 0.86 and 0.88, respectively). Three participants, including the one with
type 1 diabetes, were islet cell antibody positive. CONCLUSIONS: Clinical
characteristics did not correctly identify type 1 diabetes in this study.
Preoperative C-peptide testing may improve diabetes classification in patients
undergoing bariatric surgery; further research is needed to define the optimal C
peptide thresholds.
PMID- 28695458
TI - Perceptions of Success in Bariatric Surgery: a Nationwide Survey Among Medical
Professionals.
AB - INTRODUCTION: Various definitions for bariatric surgery (BS) success exist, with
weight loss and comorbidity resolution outcomes being the most prominent. The
study's aim was to compare how various healthcare professionals perceive success
in BS. METHODS: A 29-item, 10-point Likert scale online survey was distributed
via email to Israeli healthcare professionals involved in the different BS
aspects using common national professional organizations. These included
bariatric surgeons, dietitians, social workers, psychologists, psychiatrists,
primary care physicians, gastroenterologists, and nurses. Statement relevancy to
BS success was rated. An item was classed as "very important" for BS success if
at least 70% of participants rated it 8 or higher in each subgroup. Inter
observer agreement was calculated using kappa statistics. Data on specific
occupation, years-in-practice, and major workplace were collected as well.
RESULTS: A total of 155 responses was obtained. The majority of respondents were
dietitians (34.8%, n = 54), followed by bariatric surgeons (31.0%, n = 48) and
nurses (14.8%, n = 23). Most respondents work mainly at public hospitals (32.9%,
n = 51), followed by private hospitals (26.5%, n = 41). The mean years-in
practice among all healthcare professionals was 8.5 +/- 8.5 years. Overall inter
observer agreement for prioritized items in accordance to BS success among all
health professional subgroups was fair (Fleiss kappa = 0.278, P < 0.001), while
dietitians and mental health specialists showed the highest agreement rate
(Cohen's kappa = 0.592, P < 0.001). CONCLUSION: The study highlights the various
views on defining BS success by different healthcare professionals, although
there was some overlap of core outcomes prioritized by all professionals.
International uniform definitions for BS success are required.
PMID- 28695459
TI - Endoscopic Vacuum Therapy (EVT)-a New Concept for Complication Management in
Bariatric Surgery.
AB - BACKGROUND: Bariatric surgery is the most efficient therapy for morbid obesity.
Staple line and anastomotic leakage are the most feared postoperative
complications after Roux-en-Y gastric bypass and laparoscopic sleeve gastrectomy
(LSG). Traditional treatment options like revisional surgery and endoscopic stent
placement are associated with high morbidity and mortality as well as variable
success rates. Endoscopic vacuum therapy (EVT) has shown to be a new successful
and feasible treatment option for leaks of different etiology after major gastro
esophageal surgery. METHOD: We report a case of the EVT principle being applied
in a patient with three major leaks located apart from each other within the
gastric staple line after LSG for morbid obesity (BMI 62.7). EVT was initiated on
postoperative day 8. RESULTS: In total, 18 endoscopic interventions were
performed in 72 days, the vacuum sponge being replaced endoscopically every 4
days. Hospital length of stay was 106 days. No relevant procedure related
complications were observed during the course of therapy and during the follow
up. CONCLUSION: EVT of postoperative leaks in the upper GI tract has been shown
to be feasible and safe. It combines defect closure and effective drainage and
allows a periodic inspection of the wound cavity. In case of therapeutic failure,
it does not jeopardize surgical repair or stent placement. Even though the
techniques and materials used in EVT still vary considerably according to local
expertise, EVT has the potential to succeed as a nonsurgical, feasible, safe, and
effective treatment option for postoperative leaks in bariatric surgery.
PMID- 28695460
TI - Inversion Technique for the Removal of Partially Covered Self-Expandable Metallic
Stents.
AB - BACKGROUND AND AIMS: Partially covered self-expandable metallic stents (PCSEMS),
although an effective treatment for anastomotic/staple line leaks and strictures,
can be difficult to remove. This study examines the effectiveness of the
inversion technique for the removal of PCSEMS in the treatment of leaks and
strictures that occurred post-sleeve gastrectomy (SG) and Roux-en-Y gastric
bypass (RYGB). METHODS: Consecutive patients who underwent PCSEMS removal for a
leak and/or stricture post-SG or RYGB between July 2013 and December 2016 at the
Johns Hopkins Medical Institutions were reviewed. All PCSEMS removals were first
attempted via the inversion technique, which involves grasping the distal end of
the stent and inverting it through itself. RESULTS: Fourteen patients (four
males) underwent PCSEMS removal via the inversion technique for an
anastomotic/staple line leak (50%), stricture (29%) or both (21%) post-SG (79%)
or RYGB (21%). Technical success (successful removal of the stent) was achieved
in one endoscopic session for 13 of the 14 PCSEMS (93%). One PCSEMS required the
use of the stent-in-stent technique for removal. The median dwell time was 47
days (range 5-72). A distal partial occlusion developed in five patients (35%)
due to tissue overgrowth and one PCSEMS (7%) migrated, necessitating premature
removal. Eight patients (57%) experienced clinical success at follow-up, and six
patients (43%) required subsequent treatment due to persistence or recurrence of
the pathology. CONCLUSIONS: The inversion technique is a safe, effective, and
efficient method of removing PCSEMS placed to correct anastomotic/staple line
leaks and strictures post-SG and RYGB.
PMID- 28695461
TI - Is Endoscopy Really Necessary for Placing Intragastric Balloons?
AB - BACKGROUND: Gastric balloons for weight loss have historically been placed after
a screening endoscopy. However, the utility and yield of these endoscopies has
not been studied. Therefore, we wanted to evaluate the utility of screening
endoscopy and to assess patients who had balloons placed without endoscopy.
METHODS: Data was collected on two cohorts. Cohort 1 consisted of patients who
had a screening endoscopy prior to or upon balloon placement. Cohort 2 consisted
of patients who were followed after having a balloon placed under fluoroscopic
guidance without endoscopy. Balloon intolerance and findings on removal endoscopy
were assessed in both cohorts. RESULTS: In cohort 1 (n = 253), two patients had
severe symptoms on history; balloon placement was contraindicated based on
screening endoscopy findings. Eleven patients with a history of hiatal hernia and
the presence of severe belching demonstrated an insignificant hiatal hernia on
endoscopy. In cohort 2 (n = 50), all patients had an unremarkable history. Three
previously asymptomatic patients had balloon intolerance and one was found to
have a 4-cm hiatal hernia and oesophagitis upon balloon removal. Out of 194
patients, 25 were either intolerant to the balloon or had relevant findings on
removal endoscopy. Findings on screening endoscopy did not correlate with balloon
intolerance or findings on removal endoscopy. CONCLUSION: These results
demonstrate that a careful history can identify patients who may have
contraindications for balloon therapy and that balloons can be placed safely
after taking a careful history without screening endoscopy. Screening endoscopy
may not be useful in predicting balloon intolerance or potential complications.
PMID- 28695462
TI - Transgenic Mice Overexpressing the Divalent Metal Transporter 1 Exhibit Iron
Accumulation and Enhanced Parkin Expression in the Brain.
AB - Exposure to divalent metals such as iron and manganese is thought to increase the
risk for Parkinson's disease (PD). Under normal circumstances, cellular iron and
manganese uptake is regulated by the divalent metal transporter 1 (DMT1).
Accordingly, alterations in DMT1 levels may underlie the abnormal accumulation of
metal ions and thereby disease pathogenesis. Here, we have generated transgenic
mice overexpressing DMT1 under the direction of a mouse prion promoter and
demonstrated its robust expression in several regions of the brain. When fed with
iron-supplemented diet, DMT1-expressing mice exhibit rather selective
accumulation of iron in the substantia nigra, which is the principal region
affected in human PD cases, but otherwise appear normal. Alongside this, the
expression of Parkin is also enhanced, likely as a neuroprotective response,
which may explain the lack of phenotype in these mice. When DMT1 is overexpressed
against a Parkin null background, the double-mutant mice similarly resisted a
disease phenotype even when fed with iron- or manganese-supplemented diet.
However, these mice exhibit greater vulnerability toward 6-hydroxydopamine
induced neurotoxicity. Taken together, our results suggest that iron accumulation
alone is not sufficient to cause neurodegeneration and that multiple hits are
required to promote PD.
PMID- 28695463
TI - Effects of exercise training on anabolic and catabolic markers in patients with
chronic heart failure: a systematic review.
AB - Decreased anabolism because of alterations in the insulin-like growth factor 1
(IGF-1)/growth hormone (GH) axis and increased catabolism induced by
proinflammatory cytokines like tumor necrosis factor alpha (TNF-alpha) and
interleukin 6 (IL-6) have been reported to contribute to muscle wasting in
chronic heart failure (CHF). However, it is unclear whether exercise training
could modulate anabolic and catabolic markers in CHF patients. The purpose of
this study was to investigate the effects of exercise intervention on anabolic
and catabolic markers for patients with CHF. Literatures were systematically
searched in electronic databases and relevant references. Only published
randomized controlled trials (RCTs) focusing on exercise training for CHF were
eligible for inclusion. Outcome measurements included serum level and muscle
biopsy of TNF-alpha, IL-6, GH, and IGF-I. Of the six included studies, four
showed no significant difference between exercise group and control group in the
serum levels of TNF-alpha, IL-6, GH, and IGF-I. However, two studies showed
significant reduction in TNF-alpha and IL-6 and increase in IGF-I by local
skeletal muscle biopsy. We conclude that the decreases in catabolic markers and
increases in anabolic after exercise training were evident only by local skeletal
muscle biopsy. More RCTs on dose-response relation of exercise programs are
needed to further optimize anabolic and anti-inflammatory benefits of exercise
training in patients with CHF.
PMID- 28695464
TI - Improving Adherence to Treatment and Reducing Economic Costs of Hypertension: The
Role of Olmesartan-Based Treatment.
AB - Poor adherence to antihypertensive treatment is the single most important factor
of unsatisfactory blood pressure (BP) control. This review focuses on therapy
related factors affecting adherence and suggests how to improve it with a wise
choice of treatment schedule. Complex drug treatment schemes, poor tolerability
and drug substitutions are frequent causes of poor adherence which, in turn,
causes insufficient BP control, greater incidence of cardiovascular events and,
finally, higher global health costs. The effects of prescribing generic drugs and
of drug substitutions on adherence is also discussed. In terms of adherence,
generic drugs do not seem to be better than branded drugs, unless patients have
to bear very high "out of pocket" expenses to buy original drugs, suggesting no
advantages in switching drug with the mere goal of reducing the cost of therapy.
An important role in improving adherence (and thus cardiovascular events and
health expenditure) is also played by the availability of fixed-dose
combinations; among antihypertensive drugs, angiotensin receptor blockers (ARBs)
are those associated with higher levels of adherence and persistence. Among ARBs,
olmesartan stands out for a wide choice of effective fixed-dose combinations.
PMID- 28695465
TI - Trichoderma for climate resilient agriculture.
AB - Climate change is one of the biggest challenges of the twenty-first century for
sustainable agricultural production. Several reports highlighted the need for
better agricultural practices and use of eco-friendly methods for sustainable
crop production under such situations. In this context, Trichoderma species could
be a model fungus to sustain crop productivity. Currently, these are widely used
as inoculants for biocontrol, biofertilization, and phytostimulation. They are
reported to improve photosynthetic efficiency, enhance nutrient uptake and
increase nitrogen use efficiency in crops. Moreover, they can be used to produce
bio-energy, facilitate plants for adaptation and mitigate adverse effect of
climate change. The technological advancement in high throughput DNA sequencing
and biotechnology provided deep insight into the complex and diverse biotic
interactions established in nature by Trichoderma spp. and efforts are being made
to translate this knowledge to enhance crop growth, resistance to disease and
tolerance to abiotic stresses under field conditions. The discovery of several
traits and genes that are involved in the beneficial effects of Trichoderma spp.
has resulted in better understanding of the performance of bioinoculants in the
field, and will lead to more efficient use of these strains and possibly to their
improvement by genetic modification. The present mini-review is an effort to
elucidate the molecular basis of plant growth promotion and defence activation by
Trichoderma spp. to garner broad perspectives regarding their functioning and
applicability for climate resilient agriculture.
PMID- 28695466
TI - Oxidative stress-dependent contribution of HMGB1 to the interplay between
apoptosis and autophagy in diabetic rat liver.
AB - The progression of oxidative stress, resulting cell damage, and cell death
underlies the etiology of liver damage/dysfunction as a complication of diabetes.
High-mobility group box 1 (HMGB1) protein, a chromatin-binding nuclear protein
and damage-associated molecular pattern molecule, is integral to oxidative stress
and signaling pathways regulating cell death and cell survival. We previously
found that in streptozotocin (STZ)-induced diabetic rats, reduction of oxidative
stress after melatonin administration lowered necrotic cell death and increased
expression of HMGB1 and hepatocellular damage. In the present study, we examined
whether alleviation of diabetes-attendant oxidative stress and ensuing change in
HMGB1 expression influence the dynamic equilibrium between apoptosis/autophagy
and liver damage. We observed that elevated HMGB1 protein levels in diabetic rat
liver accompanied increased interactions of HMGB1 with TLR4 and RAGE, and
activation of the intrinsic apoptotic pathway and Beclin 1-dependent autophagy.
The absence of p62 degradation in diabetic rat liver pointed to defective
autophagy which was responsible for lower autophagosome/autophagolysosome
formation and an increased apoptosis/autophagy ratio. Compared to diabetic rats,
in melatonin-treated diabetic rats, the structure of liver cells was preserved,
HMGB1/TLR4 interaction and downstream apoptotic signaling were significantly
reduced, HMGB1/Beclin 1 colocalization and interactions were augmented and Beclin
1-mediated autophagy, mithophagy in particular, were increased. We concluded that
in mild oxidative stress, HMGB1 is cytoprotective, whereas in intense oxidative
stress, HMGB1 actions promote cell death and liver damage. Since reduced HMGB1
binds to RAGE but not to TLR4, redox modification of HMGB1 as a mechanism
regulating the cross-talk between apoptosis and autophagy in diabetes is
discussed.
PMID- 28695467
TI - New route for the synthesis of new cyanoimino- and cyanoaminopyrimidines.
AB - A novel series of 4-aryl-2-cyanoimino-3,4-dihydro-1H-pyrimidines (aryl-CIDHPMs)
was synthesized using a new method via the one-pot three-component reaction of
cyanoguanidine with malononitrile and aromatic aldehydes using sodium methoxide
as catalyst. These new aryl-CIDHPMs were also prepared by a classical route via
reaction of cyanoguanidine with the corresponding arylidenemalononitriles under
our conditions. In the same manner, the reaction of cyanoguanidine with
cyclohexylidenemalononitrile and/or isatinylidenemalononitrile afforded new spiro
pyrimidines 9 and 10, respectively. A new series of polyfunctionalized 2
cyanoaminopyrimidines was obtained from the reaction of cyanoguanidine with
cinnamaldehyde and/or ethoxyalkylenemalononitriles.
PMID- 28695468
TI - In vitro antiproliferative study of novel adamantyl pyridin-4-ones.
AB - The preparation of several N-aryl-substituted (phenyl, p-methylphenyl, p
methoxyphenyl, p-nitrophenyl, p-aminophenyl, p-hydroxyphenyl) 3-hydroxy-2
methylpyridin-4-ones as well as their adamantyl derivatives is described, and
their in vitro antitumor properties were investigated. The compounds were
synthesized in good yields using efficient synthetic routes and methods. Prepared
derivatives were evaluated in an antiproliferative in vitro study on 4 cancer
cell lines, namely HCT 116 (colon carcinoma), H 460 (lung carcinoma), MCF-7
(breast carcinoma) and K562 (chronic myelogenous leukemia). All tested compounds
showed antiproliferative activity ranging from moderate to strong on all
inspected cell lines with 4 adamantane containing derivatives being active and
selective at low micromolar IC[Formula: see text] concentrations on HCT 116, H
460 and MCF-7. LDH cytotoxicity assay revealed that cytotoxic effects occur after
48 h of exposure. It was shown that there was no change in caspase activity in
the treated cells, but there were changes in the cell cycle. All treated samples
showed reduced number of cells in the S phase with increased G0/G1 (4b, 5a, 5b)
and G2/M (4a) phase.
PMID- 28695469
TI - Older Workers and Caregiving in a Global Context.
PMID- 28695470
TI - Screening novel stress granule regulators from a natural compound library.
PMID- 28695471
TI - Ocrelizumab and Other CD20+ B-Cell-Depleting Therapies in Multiple Sclerosis.
AB - Selective depletion of CD20+ B cells by anti-CD20 monoclonal antibodies as
monotherapy in multiple sclerosis (MS) profoundly suppresses acute inflammatory
disease activity and signifies an important advance in the treatment of relapsing
remitting MS. Ocrelizumab, a humanized anti-CD20 monoclonal antibody, is also the
first proven therapy to lessen disability progression in primary progressive MS-a
breakthrough for patients with a disease that had no proven therapy. Ocrelizumab
is generally well tolerated, with the most common adverse events experienced
being infusion reactions and infections. In ocrelizumab trials in MS a numerical
imbalance in the risk of malignancies was observed. In this article, we review
advances in anti-CD20 B-cell-depleting biological therapies for MS, including
ocrelizumab, rituximab, and ofatumumab.
PMID- 28695472
TI - Assessing Repair in Multiple Sclerosis: Outcomes for Phase II Clinical Trials.
AB - Multiple Sclerosis (MS) pathology is complex and includes inflammatory processes,
neurodegeneration, and demyelination. While multiple drugs have been developed to
tackle MS-related inflammation, to date there is scant evidence regarding which
therapeutic approach, if any, could be used to reverse demyelination, foster
tissue repair, and thus positively impact on chronic disability. Here, we
reviewed the current structural and functional markers (magnetic resonance
imaging, positron emission tomography, optical coherence tomography, and visual
evoked potentials) which could be used in phase II clinical trials of new
compounds aimed to foster tissue repair in MS. Magnetic transfer ratio recovery
in newly formed lesions currently represents the most widely used biomarker of
tissue repair in MS, even if other markers, such as optical coherence tomography
and positron emission tomography hold great promise to complement magnetic
transfer ratio in tissue repair clinical trials. Future studies are needed to
better characterize the different possible biomarkers to study tissue repair in
MS, especially regarding their pathological specificity, sensitivity to change,
and their relationship with disease activity.
PMID- 28695473
TI - Transverse tubule remodelling: a cellular pathology driven by both sides of the
plasmalemma?
AB - Transverse (t)-tubules are invaginations of the plasma membrane that form a
complex network of ducts, 200-400 nm in diameter depending on the animal species,
that penetrates deep within the cardiac myocyte, where they facilitate a fast and
synchronous contraction across the entire cell volume. There is now a large body
of evidence in animal models and humans demonstrating that pathological
distortion of the t-tubule structure has a causative role in the loss of myocyte
contractility that underpins many forms of heart failure. Investigations into the
molecular mechanisms of pathological t-tubule remodelling to date have focused on
proteins residing in the intracellular aspect of t-tubule membrane that form
linkages between the membrane and myocyte cytoskeleton. In this review, we shed
light on the mechanisms of t-tubule remodelling which are not limited to the
intracellular side. Our recent data have demonstrated that collagen is an
integral part of the t-tubule network and that it increases within the tubules in
heart failure, suggesting that a fibrotic mechanism could drive cardiac
junctional remodelling. We examine the evidence that the linkages between the
extracellular matrix, t-tubule membrane and cellular cytoskeleton should be
considered as a whole when investigating the mechanisms of t-tubule pathology in
the failing heart.
PMID- 28695474
TI - Statin Therapy and Risk of Intracranial Hemorrhage in Patients with Ischemic
Stroke.
PMID- 28695475
TI - Symptom modelling can be influenced by psychiatric categories: choices for
research domain criteria (RDoC).
AB - Psychiatric researchers typically assume that the modelling of psychiatric
symptoms is not influenced by psychiatric categories; symptoms are modelled and
then grouped into a psychiatric category. I highlight this primarily through
analysing research domain criteria (RDoC). RDoC's importance makes it worth
scrutinizing, and this assessment also serves as a case study with relevance for
other areas of psychiatry. RDoC takes inadequacies of existing psychiatric
categories as holding back causal investigation. Consequently, RDoC aims to
circumnavigate existing psychiatric categories by directly investigating the
causal basis of symptoms. The unique methodological approach of RDoC exploits the
supposed lack of influence of psychiatric categories on symptom modelling, taking
psychiatric symptoms as the same regardless of which psychiatric category is
employed or if no psychiatric category is employed. But this supposition is not
always true. I will show how psychiatric categories can influence symptom
modelling, whereby identical behaviours can be considered as different symptoms
based on an individual's psychiatric diagnosis. If the modelling of symptoms is
influenced by psychiatric categories, then psychiatric categories will still play
a role, a situation which RDoC researchers explicitly aim to avoid. I discuss
four ways RDoC could address this issue. This issue also has important
implications for factor analysis, cluster analysis, modifying psychiatric
categories, and symptom based approaches.
PMID- 28695476
TI - Harm and the concept of medical disorder.
AB - According to Jerome Wakefield's harmful dysfunction analysis (HDA) of medical
disorder, the inability of some internal part or mechanism to perform its natural
function is necessary, but not sufficient, for disorder. HDA also requires that
the part dysfunction be harmful to the individual. I consider several problems
for HDA's harm criterion in this article. Other accounts on which harm is
necessary for disorder will suffer from all or almost all of these problems.
Comparative accounts of harm imply that one is harmed when one is made worse off,
that is, worse off than one otherwise would have been. Non-comparative accounts
imply that one is harmed when one is put into some kind of condition or state
that is, in some way, bad in itself. I argue that whether harm is construed
comparatively or non-comparatively, HDA's harm criterion is problematic. I
tentatively conclude that an analysis of medical disorder should not make use of
the concept of harm.
PMID- 28695477
TI - Dexpanthenol: An Overview of its Contribution to Symptom Relief in Acute Rhinitis
Treated with Decongestant Nasal Sprays.
AB - : Nasal blockage is the most bothersome symptom of acute rhinitis. Nasal
decongestant sprays containing alpha-sympathomimetics, such as oxymetazoline and
xylometazoline, have a rapid onset of action. However, this effect decreases with
repeated application and, furthermore, the ciliary function of the nasal mucosa
is practically paralyzed. Dexpanthenol promotes cell proliferation and protects
the epithelium. Combining these two agents has demonstrated beneficial synergetic
effects on the symptoms of acute rhinitis. In a post hoc analysis of a large
scale double-blind, active-controlled study including 152 patients, we could
demonstrate that the benefit of added dexpanthenol appears as early as on the
third day of the combined application of xylometazoline and dexpanthenol in terms
of complete or near-to-complete freedom from symptoms. After 5 days, 47% of the
patients were cured under the combined treatment compared with only 1% under
xylometazoline monotherapy. These data show that the addition of dexpanthenol to
an alpha-sympathomimetic nasal spray not only improves its tolerability but also
further increases its effectiveness and leads to expedited cure. FUNDING:
Klosterfrau Healthcare Group.
PMID- 28695478
TI - The prognostic impact of additional intrathoracic findings in patients with
cancer-related pulmonary embolism.
AB - AIM: To assess the prevalence and prognostic significance of additional
intrathoracic findings (AIFs) in patients with cancer and pulmonary embolism
(PE). AIFs were considered alterations other than the characteristic ones
intrinsic to PE or changes in cardiovascular morphology. METHODS: Subjects have
been taken from a Spanish national multidisciplinary and multicenter study of PE
and cancer who were treated between 2004 and 2015. The endpoint was the
appearance of serious complications or death within 15 days. RESULTS: The
registry contains 1024 eligible patients; 41% diagnosed by computed tomography
pulmonary angiography versus 59% by non-angiographic CT. Serious complications
occurred within 15 days in 18.9%, [95% confidence interval (CI), 16.6-21.4%] and
9.5% (95% CI 7.9-11.5%) died. At least one AIF was seen in 72.6%. The most common
AIFs were as follows: pulmonary nodules (30.9%), pleural effusion (30.2%), tumor
progression (28.3%), atelectasis (19.0%), pulmonary infarct (15.2%), emphysema
(13.4%), pulmonary lymphangitic carcinomatosis (4.5%), and pneumonia (6.1%).
Patients with AIF exhibited a higher complication rate at 15 days: 21.9% versus
13.0%, odds ratio (OR) 1.8 (95% CI 1.2-2.8), P = 0.03, and 15-day mortality:
15.0% versus 7.3%, OR 1.9 (95% CI 1.1-3.2), P = 0.020. Patients with pneumonia,
pneumothorax, pulmonary edema, pulmonary nodules, tumor progression, pulmonary
fibrosis, and pleural effusion showed an excess of adverse events. CONCLUSIONS:
Additional intrathoracic findings are highly prevalent and significantly impact
prognosis in patients with PE and cancer, making them germane to the
classification of this population.
PMID- 28695479
TI - Initial experience using a robotic-driven laparoscopic needle holder with
ergonomic handle: assessment of surgeons' task performance and ergonomics.
AB - PURPOSE: The objective of this study is to assess the surgeons' performance and
ergonomics during the use of a robotic-driven needle holder in laparoscopic
suturing tasks. METHODS: Six right-handed laparoscopic surgeons with different
levels of experience took part in this study. Participants performed a set of
three different intracorporeal suturing tasks organized in ten trials during a
period of five weeks. Surgeons used both conventional (Conv) and robotic (Rob)
laparoscopic needle holders. Precision using the surgical needle, quality of the
intracorporeal suturing performance, execution time and leakage pressure for the
urethrovesical anastomosis, as well as the ergonomics of the surgeon's hand
posture, were analyzed during the first, fifth and last trials. RESULTS: No
statistically significant differences in precision and quality of suturing
performance were obtained between both groups of instruments. Surgeons required
more time using the robotic instrument than using the conventional needle holder
to perform the urethrovesical anastomosis, but execution time was significantly
reduced after training ([Formula: see text] 0.05). There were no differences in
leakage pressure for the anastomoses carried out by both instruments. After
training, novice surgeons significantly improved the ergonomics of the wrist
([Formula: see text] 0.05) and index finger (Conv: 36.381[Formula: see text],
Rob: 30.389[Formula: see text]; p = 0.024) when using the robotic instrument
compared to the conventional needle holder. CONCLUSIONS: Results have shown that,
although both instruments offer similar technical performance, the robotic-driven
instrument results in better ergonomics for the surgeon's hand posture compared
to the use of a conventional laparoscopic needle holder in intracorporeal
suturing.
PMID- 28695480
TI - Finger-attachment device for the feedback of gripping and pulling force in a
manipulating system for brain tumor resection.
AB - PURPOSE: Development and evaluation of an effective attachment device for a
bilateral brain tumor resection robotic surgery system based on the sensory
performance of the human index finger in order to precisely detect gripping- and
pulling-force feedback. METHODS: First, a basic test was conducted to investigate
the performance of the human index finger in the gripping- and pulling-force
feedback system. Based on the test result, a new finger-attachment device was
designed and constructed. Then, discrimination tests were conducted to assess the
pulling force and the feedback on the hardness of the gripped material. RESULTS:
The results of the basic test show the application of pulling force on the side
surface of the finger has an advantage to distinguish the pulling force when the
gripping force is applied on the finger-touching surface. Based on this result, a
finger-attachment device that applies a gripping force on the finger surface and
pulling force on the side surface of the finger was developed. By conducting a
discrimination test to assess the hardness of the gripped material, an operator
can distinguish whether the gripped material is harder or softer than a normal
brain tissue. This will help in confirming whether the gripped material is a
tumor. By conducting a discrimination test to assess the pulling force, an
operator can distinguish the pulling-force resistance when attempting to pull off
the soft material. Pulling-force feedback may help avoid the breaking of blood
pipes when they are trapped in the gripper or attached to the gripped tissue.
CONCLUSION: The finger-attachment device that was developed for detecting
gripping- and pulling-force feedback may play an important role in the
development of future neurosurgery robotic systems for precise and safe resection
of brain tumors.
PMID- 28695481
TI - A Novel Rat Model of Nonalcoholic Fatty Liver Disease Constructed Through
CRISPR/Cas-Based Hydrodynamic Injection.
AB - CRISPR/Cas technology has been widely used in generating conventional and
conditional gene knockout animals through germline mutation. A recent study has
demonstrated that CRISPR/Cas system also worked on nongermline mutation in mice
liver via hydrodynamic injection of vector plasmid to blood circulation. However,
whether this is also applied to rat and what is the optimal concentration of
vector plasmid still need to be studied. Here, we attempted to use pX330-Pten
plasmid to knock down the expression of Pten in rat liver for generation of
nonalcoholic fatty liver disease (NAFLD) rat model. A range of pX330-Pten dosages
(75, 150 and 300 MUg/100 g) in 10 ml of saline water was injected into the blood
circulation of SD rats within 30 s by tail vein injection. The data showed that,
9 weeks after injection, no differences of TC, AST and ALT were found between
control and the treatment groups (low-dose, mid-dose, high-dose and fat-diet
groups). However, the high-dose group revealed severe lipid deposition and
significant knockdown of Pten, which was validated by western blot and real-time
PCR. Notably, lipid deposition and Pten knockdown were detected in the liver of
animals from the high-dose group as early as 6 weeks after injection. Taken
together, our findings demonstrated that hydrodynamic injection of pX330-Pten
plasmid at the dosage of 300 MUg/100 g can knock down the expression of Pten in
rat liver efficiently, resulting in lipid deposition as well as NAFLD. Taken
together, this study presents a novel and efficient method to edit genome in rat
liver.
PMID- 28695482
TI - Role of Apolipoproteins and alpha-Synuclein in Parkinson's Disease.
AB - Parkinson's disease (PD) is a progressive brain disorder that interferes with
activities of normal life. The main pathological feature of this disease is the
loss of more than 80% of dopamine-producing neurons in the substantia nigra (SN).
Dopaminergic neuronal cell death occurs when intraneuronal, insoluble, aggregated
proteins start to form Lewy bodies (LBs), the most important component of which
is a protein called alpha-synuclein (alpha-syn). alpha-Syn structurally contains
hexameric repeats of 11 amino acids, which are characteristic of apolipoproteins
and thus alpha-syn can also be considered an apolipoprotein. Moreover,
apolipoproteins seem to be involved in the incidence and development of PD. Some
apolipoproteins such as ApoD have a neuroprotective role in the brain. In PD,
apoD levels increase in glial cells surrounding dopaminergic cells. However,
elevated levels of some other apolipoproteins such as ApaA1 and ApoE are reported
as a vulnerability factor of PD. At present, when a clinical diagnosis of PD is
made, based on symptoms such as shaking, stiff muscles and slow movement, serious
damage has already been done to nerve cells of the SN. The diagnosis of PD in its
earlier stages, before this irreversible damage, would be of enormous benefit for
future treatment strategies designed to slow or halt the progression of PD. This
review presents the roles of apolipoproteins and alpha-syn in PD and how some of
them could potentially be used as biomarkers for PD.
PMID- 28695483
TI - Diagnosis and management of treatment-refractory hypothyroidism: an expert
consensus report.
AB - There is a frequently encountered subset of hypothyroid patients who are
refractory to standard thyroid hormone replacement treatment and require
unexpectedly high doses of levothyroxine. In addition to clinical situations
where hypothyroid patients are non-compliant, or where there is the possibility
of excipient-induced disease exacerbation (gluten/celiac disease), therapeutic
failure may be due to impaired absorption of the administered drug. The common
approach to managing patients with unusual thyroxine needs is to escalate the
dose of levothyroxine until targeted TSH levels are achieved. This approach can
increase the risk for prolonged exposure to supratherapeutic doses of
levothyroxine, which increase the chances of adverse outcomes. Repeated
adjustments of levothyroxine can also escalate the costs of treatment, as
frequent office visits and laboratory tests are required to determine and
maintain the desired dose. Clinicians should take a systematic approach to
managing patients whom they suspect of having treatment-refractory
hypothyroidism. This may include searching for, and adjusting, occult medical
conditions and/or other factors that may affect the absorption of levothyroxine,
before up-titrating the dose of traditional levothyroxine therapy. Depending on
the underlying pathology, another approach that may be considered is to try
alternative formulations of levothyroxine that are less susceptible to
intolerance issues related to excipients, or, in some cases, to malabsorption.
The early discovery of these factors via a thoughtful patient work-up may avoid
unnecessary thyroid medication adjustments and their consequences for both
patients and clinicians.
PMID- 28695484
TI - Use of testosterone gel compared to intramuscular formulation for puberty
induction in males with constitutional delay of growth and puberty: a preliminary
study.
AB - PURPOSE: Constitutional delay of growth and puberty (CDGP) treatment include
observation or therapy with intramuscular testosterone (IMTT). No data are
available about transdermal testosterone gel (TTG). The aim of our study was to
analyze the use of TTG in males with CDGP. METHODS: 73 boys with CDGP were
divided into three groups: IMTT treated with 50 mg i.m. testosterone; TTG with 10
mg daily 2% testosterone transdermal gel, and no treatment (CNT). All subjects
were observed at baseline and after 6 months. RESULTS: The height velocity after
treatment were statistically higher in both IMTT and TTG compared to CNT, while
CNT showed higher increase of the testicular volume. No other differences were
recorded between IMTT and TTG. CONCLUSIONS: To our knowledge this is the first
study on use of TTG for pubertal activation on CDGP population. Our preliminary
data confirm the efficacy of short-term Testosterone gel treatment to induce
puberty compared to conventional treatment.
PMID- 28695485
TI - New Opportunities in Exposure Assessment of Occupational Epidemiology: Use of
Measurements to Aid Exposure Reconstruction in Population-Based Studies.
AB - PURPOSE OF REVIEW: Exposure assessment efforts in population-based studies are
increasingly incorporating measurements. The published literature was reviewed to
identify the measurement sources and the approaches used to incorporate
measurements into these efforts. RECENT FINDINGS: The variety of occupations and
industries in these studies made collecting participant-specific measurements
impractical. Thus, the starting point was often the compilation of large
databases of measurements from inspections, published literature, and other
exposure surveys. These measurements usually represented multiple occupations,
industries, and worksites, and spanned multiple decades. Measurements were used
both qualitatively and quantitatively, dependent on the coverage and quality of
the data. Increasingly, statistical models were used to derive job-, industry-,
time period-, and other determinant-specific exposure concentrations.
Quantitative measurement-based approaches are increasingly replacing expert
judgment, which facilitates the development of quantitative exposure-response
associations. Evaluations of potential biases in these measurement sources, and
their representativeness of typical exposure situations, warrant additional
examination.
PMID- 28695486
TI - Policies to Promote Active Travel: Evidence from Reviews of the Literature.
AB - PURPOSE OF REVIEW: While many levels of government recognize that walking and
cycling (active travel) are critical to healthy cities, a continued challenge is
to identify and prioritize strategies that will increase walking and cycling for
transportation. We review evidence on policies that can increase active travel.
RECENT FINDINGS: The reviews included here conclude that policies related to
active travel may operate at various levels of the socio-ecological framework,
including society, cities, routes or individuals. The provision of convenient,
safe and connected walking and cycling infrastructure is at the core of promoting
active travel, but policies may work best when implemented in comprehensive
packages. There is strong evidence that active travel can result in substantial
health benefits. However, there remains considerable uncertainty about the exact
effects of specific policies on walking or cycling rates or safety. Further
research is needed to quantify the impact of specific policies or packages of
policies, especially across different settings or for different population
segments.
PMID- 28695487
TI - The Urban Heat Island: Implications for Health in a Changing Environment.
AB - PURPOSE OF REVIEW: The Urban Heat Island (UHI) is a well-studied phenomenon,
whereby urban areas are generally warmer than surrounding suburban and rural
areas. The most direct effect on health from the UHI is due to heat risk, which
is exacerbated in urban areas, particularly during heat waves. However, there may
be health benefits from warming during colder months. This review highlights
recent attempts to quantitatively estimate the health impacts of the UHI and
estimations of the health benefits of UHI mitigation measures. RECENT FINDINGS:
Climate change, increasing urbanisation and an ageing population in much of the
world, is likely to increase the risks to health from the UHI, particularly from
heat exposure. Studies have shown increased health risks in urban populations
compared with rural or suburban populations in hot weather and a disproportionate
impact on more vulnerable social groups. Estimations of the impacts of various
mitigation techniques suggest that a range of measures could reduce health
impacts from heat and bring other benefits to health and wellbeing. The impact of
the UHI on heat-related health is significant, although often overlooked,
particularly when considering future impacts associated with climate change.
Multiple factors should be considered when designing mitigation measures in urban
environments in order to maximise health benefits and avoid unintended negative
effects.
PMID- 28695488
TI - Brain structure abnormalities in young women who presented conduct disorder in
childhood/adolescence.
AB - The phenotype and genotype of antisocial behavior among females are different
from those among males. Previous studies have documented structural brain
alterations in males with antisocial behavior, yet little is known about the
neural correlates of female antisocial behavior. The present study examined young
women who had presented conduct disorder (CDW) prior to age 15 to determine
whether brain abnormalities are present in adulthood and whether the observed
abnormalities are associated with comorbid disorders or maltreatment that
typically characterize this population. Using magnetic resonance imaging and
voxel-based morphometry, we compared gray matter volumes (GMV) of 31 women who
presented CD by midadolescence and 25 healthy women (HW), age, on average, 23
years. Participants completed structured, validated interviews to diagnose mental
disorders, and validated questionnaires to document physical and sexual abuse.
Relative to HW, CDW presented increased GMV in the left superior temporal gyrus
that was associated with past alcohol and drug dependence, current use of alcohol
and drugs, and current anxiety and depression symptoms and maltreatment.
Additionally, CDW displayed reduced GMV in lingual gyrus, hippocampus, and
anterior cingulate cortex that was associated with past comorbid disorders,
current alcohol and drugs use, current anxiety and depression symptoms, and
maltreatment. The CDW also presented reduced total GMV that was associated with
past comorbid disorders and current anxiety/depression symptoms. Alterations of
brain structure were observed among young adult females with prior CD, relative
to HW, all of which were associated with internalizing and externalizing
disorders and maltreatment that typically accompany CD.
PMID- 28695489
TI - Lack of human cytomegalovirus expression in single cells from glioblastoma tumors
and cell lines.
AB - The relationship between human cytomegalovirus (HCMV) and glioblastoma (GBM) is
an ongoing debate with extensive evidence supporting or refuting its existence
through molecular assays, pre-clinical studies, and clinical trials. We focus
primarily on the crux of the debate, detection of HCMV in GBM samples using
molecular assays. We propose that these differences in detection could be
affected by cellular heterogeneity. To take this into account, we align the
single-cell RNA sequencing (scRNA-seq) reads from five GBM tumors and two cell
lines to HCMV and analyze the alignments for evidence of (i) complete viral
transcripts and (ii) low-abundance viral reads. We found that neither tumor nor
cell line samples showed conclusive evidence of full HCMV viral transcripts. We
also identified low-abundance reads aligned across all tumors, with two tumors
having higher alignment rates than the rest of the tumor samples. This work is
meant to rigorously test for HCMV RNA expression at a single cell level in GBM
samples and examine the possible utility of single cell data in tumor virology.
PMID- 28695490
TI - Role of Cys73 in the thermostability of farnesyl diphosphate synthase from
Geobacillus stearothermophilus.
AB - Farnesyl diphosphate synthase (FPPase) is an enzyme that catalyzes the
condensation between one molecule of dimethylallyl diphosphate (DMAPP) and two
molecules of isopentenyl diphosphate (IPP) to produce farnesyl diphosphate (FPP).
FPP is an important precursor in the isoprenoid synthesis pathway. In this study,
the crystal structure of FPPase from Geobacillus stearothermophilus (GsFPPase)
was determined at 2.31 A resolution. The structure of GsFPPase shows a three
layered all alpha-helical fold and conserved functional domains similar to other
prenyltransferases. We have analyzed the structural features of GsFPPase related
to thermostability and compared it with those of human and avian mesophilic
FPPases. "Semi-conserved" regions which appear to be possible features
contributing to the thermostability of FPPase were found.
PMID- 28695491
TI - Identification and characterization of the Chinese giant salamander (Andrias
davidianus) miRNAs by deep sequencing and predication of their targets.
AB - MicroRNAs (miRNAs) are non-coding small RNA of approximately 22 nt in length.
They are considered as key regulators for gene expression at the post
transcriptional level and play an important role in the regulation of many
fundamental biological processes. Andrias davidianus, as one of the largest
amphibian on earth, may represent the transitional type of animal from aquatic to
terrestrial life, but so far, no miRNA has been identified in the species. In
this study, Illumina deep sequencing was used for high-throughput analysis of
miRNAs in a pooled small RNA library isolated from eight tissues sample of A.
davidianus including the spleen, liver, muscle, kidney, skin, testis, gut, and
heart. In total, 6,213,146 reads were obtained, 5,962,175 of which were related
to 143 unique miRNAs, including 140 conserved and three novel A. davidianus
specific miRNAs. Among them, seven conserved miRNAs and one novel miRNA were
selected to validate their expression pattern by stem-loop qRT-PCR. Moreover,
4700 potential target genes were predicted for 143 A. davidianus miRNAs; GO
enrichment analysis and KEGG pathway showed that most of the targets are involved
in diverse biological processes including ubiquitin-mediated proteolysis, FOXO
signaling pathway, tight junction, and spliceosome. This study provides the first
large-scale identification and characterization of A. davidianus miRNAs, and
predicted their potential target genes; it will lay a valuable foundation for
future understanding the role of these miRNAs on regulating diverse biological
processes.
PMID- 28695492
TI - Patterns of acute poisoning with pesticides in the paediatric age group.
AB - BACKGROUND: Pesticides are identified as one of the dangerous poisons globally in
children and are associated with increased short- and long-term morbidity.
Pesticide poisoning is the most common method of self-poisoning among adults in
rural Sri Lanka, and the clinical management is associated with significant
healthcare costs to the country. There is however little data published on acute
pesticide poisoning among children in rural Sri Lanka. The current study aimed to
comprehensively evaluate clinical profiles, harmful first aid measures, emergency
clinical management, complications and outcomes related to acute pesticide
poisoning among children in the rural community of Sri Lanka. METHODS: This
multicenter study was conducted in the North Central Province of Sri Lanka
involving all children with acute pesticide poisoning and who were between 9
months and 12 years of age. Data were collected over 7 years (2007-2014), and
children from 36 hospitals were recruited. Data collection was carried out by
pretested, multi-structured, interviewer-administered questionnaires to identify
clinical profiles of children, harmful first aid measures, emergency clinical
management, reasons for delayed management, complications and outcomes of
pesticide poisoning events. RESULTS: Among 1621 children with acute poisoning,
9.5% (155) comprised children with acute pesticide poisoning. Male children
outnumbered female children, and the majority of children were less than 5 years.
Most common pesticides implicated in poisoning of children were organophosphates
and carbamates. Gastrointestinal and neurological symptoms were predominant
clinical features. Limited transport and lack of concern regarding urgency among
caregivers were leading reasons for delayed management. Most common location for
poisoning was cultivation lands. Harmful first aid measures were practiced in
32.4%. 7.1% had intentional pesticide poisoning. The case fatality rate of all
pesticide poisonings in the study was 1.9%. 58.1% of patients were transferred
between regional hospitals and teaching hospital. Cardiac and respiratory
arrests, aspiration pneumonia and convulsions were among the reported
complications. CONCLUSIONS: Acute pesticide poisoning in paediatric age group
(<12 years) is a relatively uncommon yet significant cause of child health
related morbidity and mortality in rural Sri Lanka. Patterns of poisoning
represent the pattern of pesticide use by the rural community. The practice of
harmful first aid measures by caregivers and delay in attending the emergency
department may negatively impact patient outcomes.
PMID- 28695493
TI - Effect of lower chlorinated hydroxylated-polychlorobiphenyls on development of
PC12 cells.
AB - Hydroxylated polychlorobiphenyls (OH-PCBs) are major metabolites of PCBs that are
widely distributed in the environment. While the effects of penta- to hepta
chlorinated OH-PCBs on neuronal differentiation have been widely reported, those
of lower chlorinated OH-PCBs have not been extensively studied. To investigate
the effects of lower chlorinated OH-PCBs on neuronal development, we studied the
effects of mono- to hexa-chlorinated OH-PCBs on PC12 cells. Morphological changes
were examined using an automatic system IN Cell Analyzer. Seventeen of the 20 OH
PCBs investigated promoted neuronal elongation in an OH-PCB concentration
dependent manner, while three OH-PCB congeners suppressed neuronal elongation
based on Dunnett's analysis. In particular, the top five OH-PCBs (4OH-PCB2, 4'OH
PCB3, 4'OH-PCB25, 4'OH-PCB68, and 4'OH-PCB159), which have hydroxyl groups at the
para-position and chlorine substitutions at the 2, 4, or 3' positions,
significantly promoted neuronal elongation. Moreover, these neuronal elongations
were suppressed by U0126, and phosphorylation of extracellular signal-regulated
kinase (ERK) 1/2 was observed in PC12 cells treated with 4OH-PCB2, 4'OH-PCB25,
and 4'OH-PCB159. Taken together, our results indicate that the effect of OH-PCB
on neuronal development is not dependent on the number of chlorine groups but on
the chemical structure, and the mitogen-activated kinase kinase (MEK)-ERK1/2
signaling pathway is involved in this process.
PMID- 28695494
TI - Identifying trace metal distribution and occurrence in sediments, inundated
soils, and non-flooded soils of a reservoir catchment using Self-Organizing Maps,
an artificial neural network method.
AB - The Lancang-Mekong River is a trans-boundary river which provides a livelihood
for over 60 million people in Southeast Asia. Its environmental security is vital
to both local and regional inhabitants. Efforts have been undertaken to identify
controlling factors of the distribution of trace metals in sediments and soils of
the Manwan Reservoir catchment in the Lancang-Mekong River basin. The
physicochemical attributes of 63 spatially distributed soil and sediment samples,
along with land-use, flooding, topographic, and location characteristics, were
analyzed using the Self-Organizing Map (SOM) methodology. The SOM permits the
analysis of complex multivariate datasets and gives a visual interpretation that
is generally not easy to obtain using traditional statistical methods. Across the
catchment, enrichments of trace metals are rare overall, despite the severely
enriched cadmium (Cd). The analysis of SOM showed that flooded levels and land
use types were associated with high concentrations of Cd. Sediments and inundated
soils covered with shrub and open woodlands in downstream always have a high
concentration of Cd. The results demonstrate that SOM is a useful tool that can
aid in the interpretation of complex datasets and help identify the environment
of enriched metals on a catchment scale.
PMID- 28695495
TI - Phosphorus uptake in four tree species under nitrogen addition in subtropical
China.
AB - Atmospheric N deposition is a serious problem in subtropical China where N is
present in large amounts but P is deficient. Several studies hypothesized that N2
fixers can overcome phosphorus limitation by trading fixed N2 for soil
phosphorus. In order to know whether N2 fixers could invest fixed N2 in
extracellular phosphatase production and could stimulate arbuscular mycorrhizal
fungi (AMF) to acquire soil P in N-rich subtropical China, an open-air greenhouse
experiment was carried out. Two N2 fixers (Acacia mangium and Ormosia pinnata)
and two non-N2 fixers (Schima superba and Pinus massoniana) were exposed to three
levels of N addition: 5.6 kg ha-1 a-1 (ambient N), 15.6 kg ha-1 a-1 (middle N),
and 20.6 kg ha-1 a-1 (high N). We found that the capacity of plants to acquire
soil P in N-rich subtropical China is species specific. The higher P uptake rates
were found for N2 fixers than non-N2 fixers under N addition, which were related
to the greater soil APA and higher AMF (p < 0.01) in the soil of N2 fixers.
However, with time, high N addition decreased more significant quantities of soil
microbial phospholipid fatty acids (PLFAs) in the soil of N2 fixers than that of
non-N2 fixers (p < 0.05). We conclude that N2 fixers have higher P uptake
capacity than non-N2 fixers under ambient N deposition in subtropical China.
However, continuing N deposition in the future might affect P uptake ability of
N2 fixers as high N addition would decrease soil microbial PLFAs of N2 fixers.
PMID- 28695496
TI - Comparative assessment of soil quality parameters after implementing
afforestation programme in forest areas of Hong Kong.
AB - The objective of this research is to investigate and compare the alteration of
soil parameters with and without afforestation programme in a Hong Kong forest,
analysed by Principal Component Analysis (PCA). One hundred soil samples were
collected from the following sites: Pak Ngau Shek (PNS), Shing Mun (SM), Tai Po
Kau (TPK), Tai Tong (TT) (forest with afforestation programme) and Lantau Peak
(LP) (control site). A significant difference was found in only two out of 16
parameters: pH (8.34-8.87) and PAHs (4.35-6.32 MUg/kg) by comparing the soils
taken in the forest with and without an afforestation programme implemented.
Three principle components are responsible for soil quality variations in the
studied sites. The first, second and third components included pH (0.167) and EC
(0.176), PAHs (0.331) and PAHs (0.207), respectively. This framework provides
information on the least disturbance of soil properties for the afforestation
programme. To conclude, a rigorous monitoring of soil quality is necessary to
assess forest health after an afforestation programme. Besides, in the long term,
an appropriate forest preservation programme should be implemented to achieve
rural area sustainability.
PMID- 28695497
TI - Comparison of CTAC and prone imaging for the detection of coronary artery disease
using CZT SPECT.
AB - BACKGROUND: Cadmium-zinc-telluride (CZT) cameras have improved the evaluation of
patients with chest pain. However, inferior/inferolateral attenuation artifacts
similar to those seen with conventional Anger cameras persist. We added prone
acquisitions and CT attenuation correction (CTAC) to the standard supine image
acquisition and analyzed the resulting examinations. METHODS AND RESULTS: Seventy
two patients referred for invasive coronary angiography (CAG), and who also
underwent rest/stress myocardial perfusion imaging (MPI) on a CZT camera in the
supine and prone positions plus CTAC imaging, to examine known or suspected CAD
between April 2013 and March 2014 were included. A sixteen-slice CT scan acquired
on a SPECT/CT scanner between rest and stress imaging provided data for iterative
reconstruction. Sensitivity, specificity, accuracy, and positive and negative
likelihood ratios (LRs) were calculated to compare MPI with CAG on a per-patient
basis. Per-patient sensitivity, specificity, and accuracy of supine images to
predict coronary abnormalities on CAG were 35% [95% confidence interval (CI) 19
52], 86% (95% CI 80-92), and 74% (95% CI 66-82); those of prone imaging were 65%
(95% CI 45-81), 82% (95% CI 76-87), and 78% (95% CI 68-85); and those of CTAC
were 59% (95% CI 41-71), 93% (95% CI 87-97), and 85% (95% CI 76-91),
respectively. CONCLUSIONS: Prone acquisition and CTAC images improve the ability
to assess the inferior/inferolateral area.
PMID- 28695498
TI - FMISO accumulation in tumor is dependent on glutathione conjugation capacity in
addition to hypoxic state.
AB - OBJECTIVE: 18F-fluoromisonidazole (FMISO), a well-known PET imaging probe for
diagnosis of hypoxia, is believed to accumulate in hypoxic cells via covalent
binding with macromolecules after reduction of the nitro group. Previously, we
showed the majority of 18F-FMISO was incorporated into low-molecular-weight
metabolites in hypoxic tumors, and the glutathione conjugate of reduced FMISO
(amino-FMISO-GS) distributed in the tumor hypoxic regions as revealed by imaging
mass spectrometry (IMS). The present study was conducted to clarify whether FMISO
is metabolized to amino-FMISO-GS within tumor cells and how amino-FMISO-GS
contributes to FMISO accumulation in hypoxic cells. We also evaluated the
relationship between FMISO accumulation and the glutathione conjugation-related
factors in the cells. METHODS: Tumor cells (FaDu, LOVO, and T24) were treated
with 18F-FMISO and incubated under normoxic or hypoxic conditions for 4 h. The
FMISO metabolites were analyzed with LC-ESI-MS. Several glutathione conjugation
related factors of tumor cells were evaluated in vitro. FaDu tumor-bearing mice
were intravenously injected with 18F-FMISO and the tumors were excised at 4 h
post-injection. Autoradiography, IMS and histologic studies were performed.
RESULTS: Amino-FMISO-GS was the main contributor to FMISO incorporated in hypoxic
FaDu cells in vitro and in vivo. Total FMISO uptake levels and amino-FMISO-GS
levels were highest in FaDu, followed by LOVO, and then T24 (total uptake: 0.851
+/- 0.009 (FaDu), 0.617 +/- 0.021 (LOVO) and 0.167 +/- 0.006 (T24) % dose/mg
protein; amino-FMISO-GS: 0.502 +/- 0.035 (FaDu), 0.158 +/- 0.013 (LOVO), and
0.007 +/- 0.001 (T24) % dose/mg protein). The glutathione level of FaDu was
significantly higher than those of LOVO and T24. The enzyme activity of
glutathione-S-transferase catalyzing the glutathione conjugation reaction in FaDu
was similar levels to that in LOVO, and was higher than that in T24. Quantitative
RT-PCR analysis revealed that the expression levels of efflux transporters of the
glutathione conjugate (multidrug resistance-associated protein 1) were lowest in
FaDu, followed by LOVO, and then T24. CONCLUSIONS: FMISO accumulates in hypoxic
cells through reductive metabolism followed by glutathione conjugation. We
illustrated the possibility that increased production and decreased excretion of
amino-FMISO-GS contribute to FMISO accumulation in tumor cells under hypoxic
conditions.
PMID- 28695499
TI - Quantitation of Poly(ADP-Ribose) by Isotope Dilution Mass Spectrometry.
AB - Poly(ADP-ribosyl)ation (PARylation), i.e., the formation of the nucleic acid-like
biopolymer poly(ADP-ribose) (PAR), is an essential posttranslational modification
carried out by poly(ADP-ribose) polymerases (PARPs). While PAR levels are low
under physiological conditions, they can transiently increase more than 100-fold
upon induction of genotoxic stress. The accurate quantitation of cellular PAR
with high sensitivity is of critical importance to understand the role of
PARylation in cellular physiology and pathophysiology and to determine the
pharmacodynamic efficiencies of clinically relevant PARP inhibitors, which
represent a novel class of promising chemotherapeutics. Previously, we have
developed a bioanalytical platform based on isotope dilution mass spectrometry
(LC-MS/MS) to quantify cellular PAR with unequivocal chemical specificity in
absolute terms with femtomol sensitivity (Martello et al. ACS Chem Biol 8(7):1567
1575, 2013). This method enables the analysis of steady-state levels, as well as
stress-induced levels of PAR in various biological systems including cell lines,
mouse tissues, and primary human lymphocytes. It has a wide range of potential
applications in basic research, as well as in drug development (Martello et al.
ACS Chem Biol 8(7):1567-1575, 2013; Mangerich et al. Toxicol Lett 244:56-71,
2016). Here, we present an improved and adjusted version of the original protocol
by Martello/Mangerich et al., which uses UPLC-MS/MS instrumentation.
PMID- 28695500
TI - Quantification of PARP Activity in Human Tissues: Ex Vivo Assays in Blood Cells
and Immunohistochemistry in Human Biopsies.
AB - Poly(ADP-ribosyl)ation of proteins is a posttranslational modification mediated
by poly(ADP-ribose) polymerases (PARPs) that use NAD+ as substrate to form the
negatively charged polymer of poly(ADP-ribose) (PAR). After DNA damage, PARP-1 is
responsible for approximately 90% of the total cellular PARylation activity.
Numerous studies showed activation of PARP-1 in various conditions associated
with oxidative and nitrosative stress, such as ischemia-reperfusion injury,
diabetes mellitus, and inflammation, and also proved the beneficial effects of
PARP inhibitors. Several pharmacological inhibitors of PARP moved toward clinical
testing for a variety of indications, including cardioprotection and malignant
tumors, and in late 2014, olaparib became the first PARP inhibitor approved for
human use for the therapy of ovarian cancer. These advances necessitate the
detection of PARP activation in human tissues. In the present chapter, we review
specific methods used to detect PARP activation in human circulating leukocytes
and in human tissue sections.
PMID- 28695501
TI - Detecting and Quantifying pADPr In Vivo.
AB - Poly(ADP-ribose) polymerases (PARP) participate in diverse biological processes
contributing to cellular homeostasis or exacerbating injury. PARP catalyzes the
addition of ADP-ribose molecules (pADPr) to the target proteins, a process termed
poly-ADP-ribosylation. Overactivation of PARP, as reflected by increased poly-ADP
ribosylation, accumulation of pADPr-modified proteins or free pADPr, contributes
to depletion of NAD+ and mitochondrial dysfunction, potentially leading to cell
death. Since PARP overactivation and increases in free pADPr have been identified
as key contributors to the pathobiology of many diseases, monitoring PARP-1
activation by detecting and quantifying pADPr may provide valuable mechanistic
insights as well as facilitating therapeutic drug monitoring for PARP
inhibitors.Several non-isotopic immunodetection methods for quantifying pADPr are
discussed: western blotting of poly-ADP-ribosylated proteins, cellular
localization of pADPr by immunohistochemistry, quantification of pADPr by enzyme
linked immunoassay and small scale two-dimensional gel electrophoresis.
PMID- 28695502
TI - Compartment-Specific Poly-ADP-Ribose Formation as a Biosensor for Subcellular NAD
Pools.
AB - Nicotinamide adenine dinucleotide (NAD) is vital to many cellular processes and
is distributed between distinct subcellular pools in the compartmentalized
eukaryotic cell. The detection and relative quantification of these individual
pools is difficult because of the methods usually applied, which require cell
disruption and fractionation.Here, we describe an immunochemical method to
visualize and relatively quantify subcellular NAD+ pools, which relies on the
NAD+-consuming activity of poly-ADP-ribose polymerase 1 (PARP1). We demonstrate
that this system can be readily applied to detect changes in the mitochondrial,
Golgi, endoplasmic reticulum, and peroxisomal NAD+ pools.
PMID- 28695503
TI - Cell Cycle Resolved Measurements of Poly(ADP-Ribose) Formation and DNA Damage
Signaling by Quantitative Image-Based Cytometry.
AB - Formation of poly(ADP-ribose) (PAR) marks intracellular stress signaling and is
notably induced upon DNA damage. PAR polymerases (PARPs) catalyze PAR synthesis
upon genotoxic stress and thereby recruit multiple proteins to damaged chromatin.
PAR induction is transient and antagonized by the action of PAR glycohydrolase
(PARG). Given that poly(ADP-ribosyl)ation (PARylation) is involved in genome
integrity maintenance and other vital cellular functions, but also in light of
the recent approval of PARP inhibitors for cancer treatments, reliable
measurements of intracellular PAR formation have gained importance. Here we
provide a detailed protocol for PAR measurements by quantitative image-based
cytometry. This technique combines the high spatial resolution of single-cell
microscopy with the advantages of cell population measurements through automated
high-content imaging. Such upscaling of immunofluorescence-based PAR detection
not only increases the robustness of the measurements through averaging across
large cell populations but also allows for the discrimination of subpopulations
and thus enables multivariate measurements of PAR levels and DNA damage
signaling. We illustrate how this technique can be used to assess the dynamics of
the cellular response to oxidative damage as well as to PARP inhibitor-induced
genotoxicity in a cell cycle resolved manner. Due to the possibility to use any
automated microscope for quantitative image-based cytometry, the presented method
has widespread applicability in the area of PARP biology and beyond.
PMID- 28695504
TI - Detecting Protein ADP-Ribosylation Using a Clickable Aminooxy Probe.
AB - ADP-ribosylation, a posttranslational modification catalyzed by a family of
enzymes known as poly(ADP-ribose) polymerases (PARPs, 17 in humans), regulates
diverse cellular processes. To aid in understanding the functions of ADP
ribosylation in cells, we developed a clickable aminooxy probe, AO-alkyne, which
detects ADP-ribosylation of acidic amino acids. AO-alkyne can be used to detect
auto-ADP-ribosylation of PARP10 in cells following Cu-catalyzed click conjugation
to an azide reporter. This method can be extended to other PARP family members
that catalyze ADP-ribosylation on acidic amino acids, providing a convenient and
direct readout of PARP activity in cells.
PMID- 28695505
TI - ADP-Ribosylated Peptide Enrichment and Site Identification: The Phosphodiesterase
Based Method.
AB - Protein ADP-ribosylation is a posttranslational modification (PTM) that plays an
important role in all major cellular processes, including DNA repair, cellular
signaling, and RNA metabolism. Site identification for this PTM has recently
become possible through the development of several mass spectrometry-based
methods, a critical step in understanding the regulatory role played by mono(ADP
ribose) (MAR), poly(ADP-ribose) (PAR), and the enzymes which make these
modifications: poly(ADP-ribose) polymerases (PARPs), best known for their role in
DNA repair and as targets for chemotherapeutic PARP inhibitors. Here, we have
described our method for enriching and identifying ADP-ribosylation events
through the use of a phosphodiesterase to digest protein-conjugated ADP-ribose
down to its attachment structure, phosphoribose. We also include here a guide to
choosing between collision-induced dissociation (CID)-, higher-energy collisional
dissociation (HCD)-, and electron-transfer dissociation (ETD)-based peptide
fragmentation for the identification of phosphoribosylated peptides.
PMID- 28695506
TI - Using Clickable NAD+ Analogs to Label Substrate Proteins of PARPs.
AB - ADP-ribosylation has been well known as an important posttranslational
modification, which is catalyzed by a family of enzymes called poly(ADP-ribose)
polymerases (PARPs). PARPs transfer of a single or multiple adenine diphosphate
ribose (ADP-ribose) units from nicotinamide adenine dinucleotide (NAD+) to
specific amino acids on substrate proteins. Through mono- or poly-ADP
ribosylation enzymatic activities, PARPs regulate various biological processes,
including DNA damage repair, chromatin remodeling, transcriptional regulation,
RNA processing and metabolism. Notably, PARP inhibitors are in clinical trials to
treat human diseases, in particular cancer. To further investigate the biological
function of PARPs, and to achieve better therapeutic effect of PARP inhibitors,
it is important to identify the physiological substrates of PARPs. Here we
describe a protocol to use clickable analog of nicotinamide adenine dinucleotide
(NAD+) that can be applied for the detection, affinity purification and
identification of substrate proteins of PARPs.
PMID- 28695507
TI - Identification of Protein Substrates of Specific PARP Enzymes Using Analog
Sensitive PARP Mutants and a "Clickable" NAD+ Analog.
AB - The PARP family of ADP-ribosyl transferases contains 17 members in human cells,
most of which catalyze the transfer of the ADP-ribose moiety of NAD+ onto their
target proteins. This posttranslational modification plays important roles in
cellular signaling, especially during cellular stresses, such as heat shock,
inflammation, unfolded protein responses, and DNA damage. Knowing the specific
proteins that are substrates for individual PARPs, as well as the specific amino
acid residues in a given target protein that are ADP-ribosylated, is a key step
in understanding the biology of individual PARPs. Recently, we developed a robust
NAD+ analog-sensitive approach for PARPs, which allows PARP-specific ADP
ribosylation of substrates that is suitable for subsequent copper-catalyzed azide
alkyne cycloaddition ("click chemistry") reactions. When coupled with proteomics
and mass spectrometry, the analog-sensitive PARP approach can be used to identify
the specific amino acids that are ADP-ribosylated by individual PARP proteins. In
this chapter, we describe the key facets of the experimental design and
application of the analog-sensitive PARP methodology to identify site-specific
modification of PARP target proteins.
PMID- 28695508
TI - Identification of ADP-Ribose Acceptor Sites on In Vitro Modified Proteins by
Liquid Chromatography-Tandem Mass Spectrometry.
AB - Protein ADP-ribosylation is a covalent, reversible posttranslational modification
(PTM) catalyzed by ADP-ribosyltransferases (ARTs). Proteins can be either mono-
or poly-ADP-ribosylated under a variety of physiological and pathological
conditions. To understand the functional contribution of protein ADP-ribosylation
to normal and disease/stress states, modified protein and corresponding ADP
ribose acceptor site identification is crucial. Since ADP-ribosylation is a
transient and relatively low abundant PTM, systematic and accurate identification
of ADP-ribose acceptor sites has only recently become feasible. This is due to
the development of specific ADP-ribosylated protein/peptide enrichment
methodologies, as well as technical advances in high-accuracy liquid
chromatography-tandem mass spectrometry (LC-MS/MS). The standardized protocol
described here allows the identification of ADP-ribose acceptor sites in in vitro
ADP-ribosylated proteins and will, thus, contribute to the functional
characterization of this important PTM.
PMID- 28695509
TI - Proteome-Wide Identification of In Vivo ADP-Ribose Acceptor Sites by Liquid
Chromatography-Tandem Mass Spectrometry.
AB - ADP-ribosylation is a posttranslational modification (PTM) that affects a variety
of cellular processes. In recent years, mass spectrometry (MS)-based proteomics
has become a valuable tool for studying ADP-ribosylation. However, studying this
PTM in vivo in an unbiased and sensitive manner has remained a difficult
challenge. Here, we describe a detailed protocol for unbiased analysis of ADP
ribosylated proteins and their ADP-ribose acceptor sites under physiological
conditions. The method relies on the enrichment of mono-ADP-ribosylated peptides
using the macrodomain Af1521 in combination with liquid chromatography-high
resolution tandem MS (LC-MS/MS). The 5-day protocol explains the step-by-step
enrichment and identification of ADP-ribosylated peptides from cell culture stage
all the way through to data processing using the MaxQuant software suite.
PMID- 28695510
TI - Poly(ADP-Ribose)-Dependent Chromatin Remodeling in DNA Repair.
AB - The tightly packed and dynamic structure of chromatin can undergo major
reorganization in response to endogenous or exogenous stimuli, such as the
regulation of transcription or the cell cycle, or following DNA damage. A fast
and local chromatin decondensation is observed upon DNA damage induced by laser
micro-irradiation. This decondensation is under the control of poly(ADP
ribosyl)ation (PARylation) by PARP1, one of the first proteins recruited at the
DNA damage sites. This chapter provides a step-by-step guide to perform and
analyze chromatin decondensation upon DNA damage induction. The protocol is based
on fluorescence microscopy of live cells expressing a core histone tagged with a
photoactivatable fluorophore. Laser micro-irradiation is used to simultaneously
induce DNA damage and activate the fluorescence signal within the irradiated
area. This photo-perturbation experiment can be easily implemented on any
confocal laser-scanning microscope equipped with a photoperturbation module. The
experimental framework can also be used to follow chromatin relaxation in
parallel with the recruitment kinetics of a protein of interest at DNA lesions in
cells co-expressing the tagged histones and a second protein of interest fused to
a different fluorescent tag.
PMID- 28695511
TI - Methods to Assess the Role of Poly(ADP-Ribose) Polymerases in Regulating
Mitochondrial Oxidation.
AB - The impact of poly(ADP-ribose) polymerase (PARP) enzymes on cellular NAD+ has
been established for almost 30 years now and its sequel, the metabolic collapse
of cells upon PARP overactivation is a nearly 20-year-old observation. However,
in the last decade there was an enormous blooming in the understanding of the
interplay between PARPs and mitochondria. Mitochondrial activity can be assessed
by a comprehensive set of methods that we aim to introduce here.
PMID- 28695512
TI - Approaches for Investigating Translational Regulation Controlled by PARP1: Biotin
Based UV Cross-Linking and Luciferase Reporter Assay.
AB - The RNA-binding proteins (RBPs) play a pivotal role in controlling gene
expression through posttranscriptional processes. As the trans-acting factors,
RBPs interact with the cis-regulatory elements located within mRNAs to regulate
mRNA translational efficiency. Adding a new-layer regulation, recent studies
suggest that poly(ADP-ribosyl)ation of the RNA-binding proteins often inhibit the
RNA-binding ability of RBPs, thus regulating RBP-dependent mRNA metabolism
including translational control. Here, we describe a biotin-based UV cross
linking method to determine if excessive accumulation of pADPr in the cell
disrupts the interaction between RBPs and their target mRNAs. In addition, we
illustrate the protocol of using the luciferase reporter assay to determine the
effect of poly(ADP-ribosyl)ation on mRNA translation.
PMID- 28695513
TI - Methodology to Identify Poly-ADP-Ribose Polymerase 1 (PARP1)-mRNA Targets by PAR
CLiP.
AB - There is a long list of important RNA-binding proteins (RBP) involved in
different steps of gene expression through posttranscriptional modifications: pre
mRNA splicing, mRNA stabilization, polyadenylation, mRNA export from nucleus to
the cytoplasm, and translation. The critical role of RNA-protein interaction
necessitates a continuous identification of proteins involved in this process.
Here we describe the identification of Poly-ADP-Ribose Polymerase 1 (PARP1) as an
RNA binding protein involved in RNA splicing.
PMID- 28695514
TI - Biochemical and Biophysical Methods for Analysis of Poly(ADP-Ribose) Polymerase 1
and Its Interactions with Chromatin.
AB - Poly (ADP-Ribose) Polymerase I (PARP-1) is a first responder to DNA damage and
participates in the regulation of gene expression. The interaction of PARP-1 with
chromatin and DNA is complex and involves at least two different modes of
interaction. In its enzymatically inactive state, PARP-1 binds native chromatin
with similar affinity as it binds free DNA ends. Automodification of PARP-1
affects interaction with chromatin and DNA to different extents. Here we describe
a series of biochemical and biophysical techniques to quantify and dissect the
different binding modes of PARP-1 with its various substrates. The techniques
listed here allow for high throughput and quantitative measurements of the
interaction of different PARP-1 constructs (inactive and automodified) with
chromatin and DNA damage models.
PMID- 28695515
TI - PARP-1 Interaction with and Activation by Histones and Nucleosomes.
AB - Poly(ADP-ribose) Polymerase 1 (PARP-1) is an abundant chromatin associated
protein, typical for most eukaryotic nuclei. The localization of PARP-1 in
chromatin and its enzymatic activation involves multiple interactions of PARP-1
with nucleosomal histones, other proteins, and DNA. We report a set of methods
designed to reconstitute PARP-1 regulation in vitro. These methods involve the
expression of PARP-1 and PARP-1-regulating proteins using bacterial and
eukaryotic systems, purification of these proteins using chromatography, testing
of individual interactions in vitro, assembly of active complexes, and
reconstitution of PARP-1 regulating reactions in vitro.
PMID- 28695516
TI - Strategies Employed for the Development of PARP Inhibitors.
AB - This chapter describes the approaches taken in the development of the first PARP
inhibitor to enter clinical trial, rucaparib (now called Rubraca), in 2003. We
describe the general principles of crystal-based drug design, the purification
and crystallization of the PARP-1 catalytic domain and how this was used to
develop highly potent PARP inhibitors, based on the nicotinamide pharmacophore.
Several methods have been used to determine the inhibitory potency in cell-free
and whole cell assays, each described with reference to its advantages and
disadvantages.
PMID- 28695517
TI - High-Throughput Colorimetric Assay for Identifying PARP-1 Inhibitors Using a
Large Small-Molecule Collection.
AB - Poly(ADP-ribose)polymerase 1 (PARP-1) protein became a popular target for
treatment of several types of cancer. A number of PARP-1 inhibitors are currently
in clinical trials. Most of them were designed competitors with NAD for a binding
site on PARP-1 molecule. This strategy resulted in a discovery of mainly
nucleotide-like PARP-1 inhibitors, which may target not only PARP-1 but also
other pathways involving NAD and other nucleotides. Many cancer types demonstrate
rapid development of resistance to NAD-like PARP-1 inhibitors. Thus,
identification and characterization of new small molecules inhibit PARP-1 with
high specificity and efficacy is important for the clinical research. We have
proposed a new approach to screen libraries for new PARP-1 inhibitors based on
histone H4-dependent PARP-1 activation. Beside identification of NAD competitors
in a small molecules collection, this approach allows finding other classes of
PARP-1 inhibitors that specifically disrupt H4-based PARP-1 activation or arrest
inactive allosteric conformation of PARP-1. Here, we present an adaptation of
this approach for a large-scale high-throughput screen.
PMID- 28695518
TI - Testing PARP Inhibitors Using a Murine Xenograft Model.
AB - Animal models are indispensable research tools for various drug discovery and
development applications. In cancer research, the growth of tumors in vivo is
necessary in order to closely modulate a potential response in humans. Ectopic
(subcutaneous) xenografting of human cancer cells into immunodeficient mice has
long been the standard model for preclinical evaluation of novel antitumor
therapeutic agents. Here, we describe the establishment and use of subcutaneous
xenograft mouse model to evaluate the antitumor activity of PARP-1 inhibitors.
PMID- 28695519
TI - In Vitro Long-Term Proliferation Assays to Study Antiproliferative Effects of
PARP Inhibitors on Cancer Cells.
AB - Cell proliferation assays are an important component of small molecule inhibitor
screens for cancer therapies. An important but often overlooked variable involves
the timing and timeframe of inhibitor treatment. Whereas many traditional
chemotherapeutics kill or inhibit proliferation on the timeframe of hours or in a
few days of treatment, more targeted therapies that affect other cancer-relevant
pathways, including differentiation or cell stress responses, can take longer,
often several days to weeks to impact cellular growth and survival. Many poly(ADP
ribose) polymerases (PARPs) are involved in cellular stress pathways; therefore,
phenotypic effects of PARP inhibition are often only observed with long-term
inhibitor treatment. Here we summarize several assays for analyzing long-term
proliferation of both adherent and suspension cells, relying either on growth in
two-dimensional tissue culture or on systems than enable growth in 3D.
PMID- 28695520
TI - Use of Inosine Monophosphate Dehydrogenase Activity Assay to Determine the
Specificity of PARP-1 Inhibitors.
AB - Inosine monophosphate dehydrogenase (IMPDH) is a rate-limiting enzyme involved in
purine nucleotide biosynthesis. It is responsible for catalyzing the oxidation of
inosine monophosphate (IMP) into xanthosine monophosphate (XMP). Concurrently,
the cofactor NAD+ is reduced to NADH. Poly(ADP-ribose) polymerase 1 (PARP-1) also
utilizes NAD+ as a substrate to synthesize poly(ADP-ribose). It has been
demonstrated that inhibition of PARP-1 activity can be an effective cancer
therapeutic. However, most PARP-1 inhibitors, including olaparib, were developed
as NAD+ analogs. Therefore, these inhibitors likely interfere with other NAD+
dependent pathways such as the one involved in de novo purine metabolism. In this
chapter, we describe a method to quantitatively measure IMPDH activity by taking
advantage of the autofluorescence of the product NADH. We use this method to
analyze the effects of olaparib and non-NAD+-like PARP-1 inhibitor (5F02) on
IMPDH activity. We found that olaparib, unlike 5F02, significantly inhibits IMPDH
activity in a dose-dependent manner. Our results suggest that IMPDH inhibition is
an off-target effect of olaparib treatment. The consequences of this effect
should be addressed by future clinical studies.
PMID- 28695521
TI - The Use of PARP Inhibitors in Cancer Therapy: Use as Adjuvant with Chemotherapy
or Radiotherapy, Use as a Single Agent in Susceptible Patients, and Techniques
Used to Identify Susceptible Patients.
AB - This chapter describes some of the techniques in use in our laboratories for the
investigation of PARP inhibitors in clinical medicine. More specifically, we are
involved in investigating the utility of PARP inhibitors in the treatment of
hematopoietic malignancies. We are also actively investigating the properties of
the PARP systems in cell biology. We begin the chapter with a very brief history
of the invention and use of PARP inhibitors. We then explain the underlying logic
of the use of PARP inhibitors either in combination with chemo- or radiotherapy
or as single agents used alone. We then provide in full detail the protocols that
we use to study PARP inhibitors in cell biology to identify patients that should
be susceptible to PARP inhibitor treatment and to manage and investigate these
patients throughout their treatment.
PMID- 28695522
TI - Purification of Recombinant Human PARP-3.
AB - The purification of poly(ADP-ribose) polymerase-3 (PARP-3) from overexpressing
cells (Sf9 insect cells, Escherichia coli) has been updated to a fast and
reproducible two chromatographic steps protocol. After cell lysis, PARP-3 protein
from the crude extract is affinity purified on a 3-aminobenzamide SepharoseTM
chromatographic step. The last contaminants and the 3-methoxybenzamide used to
elute PARP-3 from the previous affinity column are removed on the high
performance strong cations exchanger MonoQTM matrix. This step allows also the
concentration of the protein. The columns connected to an AKTATM purifier system
allow the purification of the protein in 3 days with a high-yield recovery. As
described in the protocol, more than 3 mg of pure and active human PARP-3 can be
obtained from 1.5 L of E. coli culture.
PMID- 28695523
TI - Purification of Recombinant Human PARG and Activity Assays.
AB - The purification of Poly(ADP-ribose) glycohydrolase (PARG) from overexpressing
bacteria Escherichia coli is described here to a fast and reproducible one
chromatographic step protocol. After cell lysis, GST-PARG-fusion proteins from
the crude extract are affinity purified by a Glutathione 4B Sepharose
chromatographic step. The PARG proteins are then freed from their GST-fusion by
overnight enzymatic cleavage using the preScission protease. As described in the
protocol, more than 500 MUg of highly active human PARG can be obtained from 1.5
L of E. coli culture.
PMID- 28695524
TI - Studying Catabolism of Protein ADP-Ribosylation.
AB - Protein ADP-ribosylation is a conserved posttranslational modification that
regulates many major cellular functions, such as DNA repair, transcription,
translation, signal transduction, stress response, cell division, aging, and cell
death. Protein ADP-ribosyl transferases catalyze the transfer of an ADP-ribose
(ADPr) group from the beta-nicotinamide adenine dinucleotide (beta-NAD+) cofactor
onto a specific target protein with the subsequent release of nicotinamide. ADP
ribosylation leads to changes in protein structure, function, stability, and
localization, thus defining the appropriate cellular response. Signaling
processes that are mediated by modifications need to be finely tuned and
eventually silenced and one of the ways to achieve this is through the action of
enzymes that remove (reverse) protein ADP-ribosylation in a timely fashion such
as PARG, TARG1, MACROD1, and MACROD2. Here, we describe several basic methods
used to study the enzymatic activity of de-ADP-ribosylating enzymes.
PMID- 28695525
TI - Purification of DNA Damage-Dependent PARPs from E. coli for Structural and
Biochemical Analysis.
AB - Human PARP-1, PARP-2, and PARP-3 are key players in the cellular response to DNA
damage, during which their catalytic activities are acutely stimulated through
interaction with DNA strand breaks. There are also roles for these PARPs outside
of the DNA damage response, most notably for PARP-1 and PARP-2 in the regulation
of gene expression. Here, we describe a general method to express and purify
these DNA damage-dependent PARPs from E. coli cells for use in biochemical assays
and for structural and functional analysis. The procedure allows for robust
production of PARP enzymes that are free of contaminant DNA that can interfere
with downstream analysis. The described protocols have been updated from our
earlier reported methods, most importantly to introduce PARP inhibitors in the
production scheme to cope with enzyme toxicity that can compromise the yield of
purified protein.
PMID- 28695526
TI - Identifying and Validating Tankyrase Binders and Substrates: A Candidate
Approach.
AB - The poly(ADP-ribose)polymerase (PARP) enzyme tankyrase (TNKS/ARTD5, TNKS2/ARTD6)
uses its ankyrin repeat clusters (ARCs) to recognize degenerate peptide motifs in
a wide range of proteins, thereby recruiting such proteins and their complexes
for scaffolding and/or poly(ADP-ribosyl)ation. Here, we provide guidance for
predicting putative tankyrase-binding motifs, based on the previously delineated
peptide sequence rules and existing structural information. We present a general
method for the expression and purification of tankyrase ARCs from Escherichia
coli and outline a fluorescence polarization assay to quantitatively assess
direct ARC-TBM peptide interactions. We provide a basic protocol for evaluating
binding and poly(ADP-ribosyl)ation of full-length candidate interacting proteins
by full-length tankyrase in mammalian cells.
PMID- 28695527
TI - Computational and Experimental Studies of ADP-Ribosylation.
AB - The macrodomains are a multifunctional protein family that function as receptors
and enzymes acting on poly(ADP-ribose), ADP-ribosylated proteins, and other
metabolites of nicotinamide adenine dinucleotide (NAD+). Several new functions
for macrodomains, such as nucleic acid binding and protein-protein interaction,
have recently been identified in this family. Here, we discuss methods for the
identification of new macrodomains in viruses and the prediction of their
function. This is followed by the expression and purification of these proteins
following overexpression in bacterial cells and confirmation of folding and
function using biophysical methods.
PMID- 28695529
TI - Summation of visual attributes in auditory-visual crossmodal correspondences.
AB - Crossmodal correspondences are a feature of human perception in which two or more
sensory dimensions are linked together; for example, high-pitched noises may be
more readily linked with small than with large objects. However, no study has yet
systematically examined the interaction between different visual-auditory
crossmodal correspondences. We investigated how the visual dimensions of
luminance, saturation, size, and vertical position can influence decisions when
matching particular visual stimuli with high-pitched or low-pitched auditory
stimuli. For multidimensional stimuli, we found a general pattern of summation of
the individual crossmodal correspondences, with some exceptions that may be
explained by Garner interference. These findings have applications for the design
of sensory substitution systems, which convert information from one sensory
modality to another.
PMID- 28695528
TI - NEVER forget: negative emotional valence enhances recapitulation.
AB - A hallmark feature of episodic memory is that of "mental time travel," whereby an
individual feels they have returned to a prior moment in time. Cognitive and
behavioral neuroscience methods have revealed a neurobiological counterpart:
Successful retrieval often is associated with reactivation of a prior brain
state. We review the emerging literature on memory reactivation and
recapitulation, and we describe evidence for the effects of emotion on these
processes. Based on this review, we propose a new model: Negative Emotional
Valence Enhances Recapitulation (NEVER). This model diverges from existing models
of emotional memory in three key ways. First, it underscores the effects of
emotion during retrieval. Second, it stresses the importance of sensory
processing to emotional memory. Third, it emphasizes how emotional valence -
whether an event is negative or positive - affects the way that information is
remembered. The model specifically proposes that, as compared to positive events,
negative events both trigger increased encoding of sensory detail and elicit a
closer resemblance between the sensory encoding signature and the sensory
retrieval signature. The model also proposes that negative valence enhances the
reactivation and storage of sensory details over offline periods, leading to a
greater divergence between the sensory recapitulation of negative and positive
memories over time. Importantly, the model proposes that these valence-based
differences occur even when events are equated for arousal, thus rendering an
exclusively arousal-based theory of emotional memory insufficient. We conclude by
discussing implications of the model and suggesting directions for future
research to test the tenets of the model.
PMID- 28695530
TI - The Synthesis and Structural Characterization of Graft Copolymers Composed of
gamma-PGA Backbone and Oligoesters Pendant Chains.
AB - The novel copolymers composed of poly-gamma-glutamic acid (gamma-PGA) and
oligoesters have been developed. The structures of the obtained copolymers
including variety of end groups were determined at the molecular level with the
aid of electrospray ionization multistage mass spectrometry (ESI-MSn). The
fragmentation experiment performed for the selected sodium adducts of the
copolymers confirmed that the developed methods lead to the formation of graft
copolymers composed of poly-gamma-glutamic acid (gamma-PGA) backbone and
oligoesters pendant chains. Moreover, it was established that fragmentation of
selected sodium adducts of graft copolymers proceeded via random breakage of
amide bonds along the backbone and ester bonds of the oligoesters pendant chains.
Considering potential applications of the synthesized copolymers in the area of
biomaterials, the hydrolytic degradation under laboratory conditions and in vitro
cytotoxicity tests were performed. The ESI-MSn technique applied in this study
has been proven to be a useful tool in structural studies of novel graft
copolymers as well as their degradation products. Graphical Abstract ?.
PMID- 28695531
TI - Gain Switching for a Detection System to Accommodate a Newly Developed MALDI
Based Quantification Method.
AB - In matrix-assisted laser desorption ionization time-of-flight mass spectrometry
(MALDI-TOF), matrix-derived ions are routinely deflected away to avoid problems
with ion detection. This, however, limits the use of a quantification method that
utilizes the analyte-to-matrix ion abundance ratio. In this work, we will show
that it is possible to measure this ratio by a minor instrumental modification of
a simple form of MALDI-TOF. This involves detector gain switching. Graphical
Abstract ?.
PMID- 28695532
TI - Improved Precision and Accuracy of Quantification of Rare Earth Element
Abundances via Medium-Resolution LA-ICP-MS.
AB - Laser ablation ICP-MS enables streamlined, high-sensitivity measurements of rare
earth element (REE) abundances in geological materials. However, many REE isotope
mass stations are plagued by isobaric interferences, particularly from diatomic
oxides and argides. In this study, we compare REE abundances quantitated from
mass spectra collected with low-resolution (m/Deltam = 300 at 5% peak height) and
medium-resolution (m/Deltam = 2500) mass discrimination. A wide array of
geological samples was analyzed, including USGS and NIST glasses ranging from
mafic to felsic in composition, with NIST 610 employed as the bracketing
calibrating reference material. The medium-resolution REE analyses are shown to
be significantly more accurate and precise (at the 95% confidence level) than low
resolution analyses, particularly in samples characterized by low (=68 years, median age) for HbA1c, LDL-c and
diastolic blood pressure control. CONCLUSION: This cross-sectional study
demonstrates that blood pressure and lipid goals are less often achieved than
blood glucose control in type 2 diabetic patients followed up by primary care
physicians in Switzerland. Goal attainments for HbA1c and LDL-c were not
influenced by chronic kidney disease stages, in contrast to blood pressure.
Reaching all three goals was rare (2.2%). There is a need for improvement in
blood pressure control in advanced chronic kidney disease, whereas HbA1c goals
may be loosened in the elderly and in advanced chronic kidney disease.
PMID- 28695553
TI - Healthy persons at risk for iron substitution.
PMID- 28695554
TI - The search for atrial fibrillation and its impact on public health.
AB - Atrial fibrillation may be clearly symptomatic and is easily amenable to state-of
the-art treatment, most importantly oral anticoagulation therapy for the
prevention of thromboembolism. However, atrial fibrillation may also go unnoticed
for long periods in many patients. This silent or subclinical atrial fibrillation
is nevertheless associated with thromboembolic risk just like clinically evident
atrial fibrillation. Early detection of atrial fibrillation in patients at
increased thromboembolic risk and consequent oral anticoagulation therapy may
have a significant impact on public health. This review focuses on screening
recommendations for atrial fibrillation and on the impact of silent atrial
fibrillation in various clinical scenarios.
PMID- 28695555
TI - Adherence to osteoporosis pharmacotherapy one year after osteoporotic fracture -
a Swiss trauma center secondary prevention project.
AB - AIMS OF THE STUDY: According to current evidence, one out of ten fracture
patients with osteoporosis does not sustain another fracture if he or she is on
adequate medication. However, epidemiological surveys show that only about 15 to
30% of affected patients avail themselves of the treatments. This cohort study
investigated how many fracture patients with a recommendation for
antiosteoporotic therapy effectively received treatment and the possible reasons
why the treatment was not implemented. METHODS: As part of a quality improvement
programme in a Swiss trauma centre, fracture patients were actively checked for
osteoporosis in accordance with a standardised outpatient programme. The results,
together with detailed therapy recommendations, were transmitted to each
patient's general practitioner (GP). A prospective questionnaire survey evaluated
all patients with a diagnosis of osteoporosis for subsequent realisation of
therapy 1 year after the fracture (mean +/- standard deviation; chi-square;
analysis of variance; significance level p <0.05). RESULTS: A total of 305
patients received a recommendation for antiosteoporotic therapy, of whom 18
(5.9%) died before 1 year. The questionnaire was completed for 255 out of 287
patients (follow-up 88.9%; 73.8+/-11.5 years old at the time of survey; 77.7%
female). Of these, 117 patients (45.9%) sustained a fracture of the lower
extremities and 105 patients (41.1%) a fracture of the upper extremities; 33
patients (13%) had other or multiple fractures. Fifty-two cases (20.4%) had pre
existing osteoporosis at the time of fracture. At the 1-year follow-up, 132 (52%)
patients were receiving prescribed drugs. The most frequent patient explanation
for not taking treatment (n = 123) was, in 47.2% of cases (n = 58), that none had
been prescribed; 30.1% of patients were not interested. Multivariate analysis of
verifiable factors of influence confirmed that fracture patients were treated
significantly more reliably with antiosteoporotic therapy if osteoporosis was
diagnosed with dual energy x-ray absorptiometry alone in patients with fewer
comorbidities, and that fracture patients persisted significantly more reliably
with antiosteoporotic therapies when pre-existing osteoporosis was present (R2
0.17; p <0.001). CONCLUSIONS: Following a standardised diagnostic work up for
osteoporosis as part of fracture treatment, and including the communication of
recommendations for antiosteoporotic therapy to the GP, only every second patient
actually received the proposed treatment. This appears to be better than
described in the literature but still calls for improvement. Two different
solutions appear to be possible based on these findings: to endeavour to better
inform and convince GPs about the need for treatment and/or for the diagnosing
team to initiate antiosteoporotic therapy where indicated rather than just
recommending it.
PMID- 28695556
TI - Changing trends in end-stage renal disease patients with diabetes.
AB - BACKGROUND: Worldwide, diabetes has become the most common cause of end-stage
renal disease (ESRD), yet Swiss data are largely lacking. METHODS: This
observational study examined ESRD patients with diabetes mellitus (ESRD-DM) at
end of 2009 and 2014. The prevalence and characteristics of ESRD-DM patients were
collected in all dialysis facilities in the Canton of Vaud of Switzerland in 2009
and in 2014, and the 5-year mortality rate was assessed. RESULTS: A total of 107
and 140 ESRD-DM patients underwent dialysis at end of 2009 and 2014,
respectively. Within the 5-year period a total of 167 incidental ESRD-DM patients
required dialysis, corresponding to an estimated incidental rate of 0.84/1000
person-years in the diabetic population. In 2009, all patients with ESRD-DM
underwent haemodialysis, decreasing to 96.2% in 2014, with 3.8% on peritoneal
dialysis. Age, sex, body mass index, type of diabetes, duration of diabetes,
cause of ESRD, dialysis duration, dialysis frequency, vascular access, and
glycosylated haemoglobin levels did not differ between 2009 and 2014. In 2014,
macrovascular comorbidity was reported more often than in 2009, but not
amputations. Haemoglobin level decreased significantly from 117.9 g/l to 112.3
g/l. Calcium-containing phosphate binder and angiotensin-converting enzyme
inhibitor use significantly decreased, whereas iron therapy significantly
increased with time. The 5-year mortality rate was 61.7%. Five-year survivors
were significantly younger and had a higher body mass index. CONCLUSIONS: The
growing prevalence of ESRD-DM emphasises that prevention of chronic kidney
disease and its progression should be a public health priority in Switzerland.
PMID- 28695557
TI - Impact of new technologies and experience on procedural aspects of surgical
aortic valve replacement - a process analysis.
AB - BACKGROUND: Surgical aortic valve replacement (SAVR) is the treatment of choice
in severe symptomatic aortic valve disease. New techniques and prostheses have
been recently developed to facilitate the procedure and reduce aortic cross-clamp
time (AOx). The aim of this study was to analyse the different procedural steps
in order to identify the most time-consuming part during aortic clamping time and
to compare impact of experience on procedural aspects. METHODS: AOx during SAVR
was divided into five consecutive steps. Duration of each step was measured. The
first procedural step started with clamping of the aorta and ended with the
beginning of the second step starting with the resection of the native aortic
valve. The third step started with placement of the first valve anchoring suture,
the fourth step started with tying of the first suture and the fifth and final
step started after the cut of the last suture and ended with removal of the
aortic clamp. Surgeons were divided into two groups based on their experience,
which in our analysis was defined as a total SAVR experience of more than 100
procedures. RESULTS: From March 2013 to August 2015 57 nonconsecutive patients
(33% female; age, median 71.0 years, interquartile range 65.0-76.0) undergoing
isolated SAVR for severe aortic valve stenosis in our institution were included
in this process analysis. Two different prostheses were implanted. Forty-eight
(84%) patients received a tissue valve (Perimount Magna Ease, Edwards
Lifesciences, Irvine, USA) and 9 (16%) patients received a mechanical prosthesis
(Medtronic AP 360, St-Paul, MN, USA). The mean estimated risk of mortality was
1.1% (0.7-1.6) according to the logistic EUROScore II. Overall duration of AOx
was 50.5 +/- 13.8 min, with 32.3% (16.4 +/- 5.9 min) accounting for placing the
sutures into the native annulus and the prosthetic sewing ring and 18.5% (9.2 +/-
3.0min) accounting for tying and cutting the sutures. Surgeons with more
experience performed 35 operations (61.4%) and needed an average of 44.1 +/- 11.5
min versus 60.6 +/- 11.0 min (p <0.001) for less experienced surgeons. Surgeons
with more experience needed 14.0 +/- 5.0 min for the suturing step and 8.4 +/-
2.8 min for tying the sutures compared with 20.2 +/- 5.2 min and 10.5 +/- 3.0
min, respectively, for the less experienced surgeons with (p <0.001 and p =
0.010). CONCLUSION: Placing and tying sutures in the prostheses accounts for over
half (50.8%) of AOx during isolated SAVR. Experienced surgeons have significantly
reduced AOx. This shortening is equally distributed between all five procedural
steps.
PMID- 28695558
TI - Rehabilitation in patients with pulmonary arterial hypertension.
AB - Exertional dyspnoea is a leading symptom in patients with pulmonary arterial
hypertension (PAH). Patients suffering from PAH report poor quality of life, have
skeletal muscle dysfunction and in the absence of advanced medical therapy
deteriorate progressively due to right heart failure which can lead to death. For
decades, patients with PAH were advised to avoid exercise in fear of exacerbated
right heart failure. Recently, it has been shown that a highly supervised
rehabilitation programme in expert centres leads to significant improvements in
symptoms, quality of life, exercise capacity and may even enhance haemodynamics
in selected stable patients treated with advanced regimens of PAH-targeted drugs.
As a consequence of these promising results, pulmonary rehabilitation performed
in an expert centre has been included in recent guidelines. The underlying
mechanisms are not completely understood, but positive effects can be measured in
different organ systems such as skeletal muscles, the cardiopulmonary system and
immune system (inflammation), and also on the psychological level. Thus,
improvements in 6-minute walking distance (6MWD), peak oxygen uptake (VO2 peak),
muscle strength and muscle endurance, as well as physical and mental quality of
life scores (SF-36 questionnaire) have been shown. Different training protocols
have been used. Essential are qualified patient selection in expert centres, a
low workload endurance and dumbbell (weight lifting) training avoiding strenuous
exercise and exhaustion, thorough patient education and close supervision by
experts especially during the first weeks. Adverse events may occur (e.g., pre
/syncope, arrhythmia, respiratory infections). PAH patients tend to overestimate
their physical capacity, not perceiving their own limits properly, which makes
education and expert advice even more important as exercise training can also
worsen the right heart failure. Therefore, a core issue of the multidisciplinary
rehabilitation is the close cooperation between the experienced rehabilitation
clinic offering a specialised programme for PAH patients and the PAH expert
centre, which takes care of the patient and is thoroughly involved in the
training programme. Further multicentre international randomised trials are
needed to evaluate whether this specialised programme is feasible within
different healthcare systems and to assess long term effects and survival.
PMID- 28695559
TI - Teamwork in rehabilitation - it is effective but it must be financed.
PMID- 28695560
TI - Minimally invasive extracorporeal circulation: excellent outcome and life
expectancy after coronary artery bypass grafting surgery.
AB - OBJECTIVE: Coronary artery bypass grafting (CABG) remains the gold standard for
complex revascularisation in multivessel disease. The concept of the minimally
invasive extracorporeal circulation circuit (MiECC) was introduced to minimise
pathophysiological side effects of conventional extracorporeal circulation. This
study presents early and long-term outcomes after CABG with use of MiECC in a
single-centre consecutive patient cohort. METHODS: From 1 January 2005 to 31
December 2010, 2130 patients underwent isolated CABG with MiECC at our centre. We
evaluated morbidity and mortality follow-up data with a median follow-up of 3.6
years. Kaplan-Meier curves and estimates of the primary end-point for all-cause
mortality were compared with the life expectancy of the general population.
RESULTS: Mortality in CABG patients was comparable to the general population
beginning 1 year after surgery for the whole observation period. All-cause 30-day
mortality was 0.8%. The mean estimated logistic EuroSCORE and EuroSCORE II were
5.8 +/- 8.6 and 3.0 +/- 5.1, respectively. Mean perfusion time was 71.1 +/- 23.8
min with a cross-clamp time of 44.9 +/- 16.3 min. Mortality was predicted by the
presence of diabetes mellitus (odds ratio [OR] 1.85, 95% confidence interval [CI]
1.40-2.46; p <0.001), peripheral arterial disease (OR 2.36, 95% CI 1.64-3.38; p
<0.001), severe obstructive pulmonary disease (OR 3.21, 1.42-7.24; p = 0.005),
chronic renal failure (OR 3.68, 2.49-5.43; p <0.001) and transfusion of more than
one unit of erythrocyte concentrate in the perioperative period (OR 1.46, 1.09
1.95; p = 0.015). Cerebrovascular events occurred in 36 patients (1.7%).
CONCLUSION: CABG with use of MiECC is associated with a mortality rate comparable
to the overall life expectancy of the general population. MiECC is the first
choice for routine and emergency CABG at our centre with a 30-day mortality rate
of 0.8% and a low complication rate.
PMID- 28695561
TI - Medical challenges at the end of the first ten decades of life.
AB - Demographic changes worldwide challenge the healthcare system. Advanced age is
associated with a number of biological alterations that, together with
concomitant comorbidities, increase the risk for functional decline by inducing
functional disintegration. In this concept frailty and sarcopenia play an
important role. Consequently the preservation of muscle mass and function are
prominent targets of medicine in old age. In order to professionally care for
persons in their last years of life several other factors influencing medical
decisions regarding diagnostic and treatments are important. These factors
concern the life expectancy, the person's functional status the physicians
involved in care and the family system. Balancing between over- and
undertreatment in very old patients can be optimised by a goal-oriented decision
making approach. Very old persons with poor decision making capacity might
benefit from decisions made in a team. To be able to manage the challenges
associated with the last decade of life, we need physicians who have the
knowledge, the appropriate attitude towards frail old patients and the skills to
communicate with different groups involved in care. Ideally old age medicine
should become an integrative part of a unified national medical curriculum.
PMID- 28695562
TI - Medical use of cannabis in Switzerland: analysis of approved exceptional
licences.
AB - AIMS OF THE STUDY: In recent years, the Swiss Federal Office of Public Health
(FOPH) granted exceptional licenses for the medical use of cannabinoids,
typically for 6 months with possible extensions. A systematic review of
cannabinoids for medical use commissioned by the FOPH supports the use of
cannabinoids for the treatment of chronic pain and spasticity. However, little is
known about the patients treated with cannabinoids. We aimed to study medical
uses of cannabinoids as part of the FOPH's programme of exceptional licenses.
METHODS: We examined all requests for medical use of cannabinoids sent to FOPH in
2013 and 2014. A standardised data sheet was developed to extract data from the
files of approved requests. We extracted the duration of the licence, the year it
was granted, and the payer of the therapy. At the level of the patient we
collected the date of birth, sex, region of residence, diagnosis and the
indication. Ethical approval was granted by the Ethics Committee of the Canton of
Bern. RESULTS: We analysed 1193 patients licenced for cannabinoid treatment in
2013 or 2014. During 2013, 542 patients were treated under the exceptional
licencing programme (332 requesting physicians) compared with 825 in 2014 (446
physicians). Over half of patients (685; 57%) were women. The mean age was 57
years (standard deviation 15.0), chronic pain (49%) and spasticity (40%) were the
most common symptoms, and co-medication was reported for 39% of patients. Seventy
eight different diagnoses were recorded, including multiple sclerosis (257
patients, 22%), soft tissue disorders (119, 10%), dorsalgia (97, 8.1%), spinal
muscular atrophy (65, 5.5%) and paraplegia/tetraplegia (62, 5.2%). Licence
extensions were granted to 143 patients (26.4%) in 2013 and 324 patients (39.3%)
in 2014. There were substantial regional variations of the rates of patients
treated with cannabinoids. On average, eight patients per 100 000 residents
received an exceptional licence. Most patients (1083, 91%) paid out of pocket.
CONCLUSIONS: Exceptional licences for medical use of cannabinoids have increased
substantially in Switzerland, with the programme including patients with a wide
range of conditions.
PMID- 28695563
TI - Bone targeted therapies in advanced breast cancer
AB - Bone targeted therapies are of increasing importance, not only for bone health in
the clinical course of breast cancer, but recently also in the adjuvant setting
as preventative, anticancer and prognosis-improving agents. It is well
established that women with advanced breast cancer receive bisphosphonates or
denosumab to prevent therapy-related osteoporosis. As many as 70% of these
patients suffer from bone metastases and receive bone targeted agents in order to
prevent skeletal related events (SREs), which are debilitating or diminish the
quality of life. A number of trials provided guidance, identifying zoledronic
acid as the most efficient bisphosphonate, showing that intravenous
bisphosphonate administration is superior to oral intake and illustrating the
different safety profile of denosumab, which has been reported to be more
beneficial than zoledronic acid in delaying the time to first and subsequent
(multiple) SREs. New studies have suggested that bone targeted therapies improve
rates of overall survival and contribute to preventing recurrence of breast
cancer at all sites. Increased bone turnover is both a consequence and a driving
factor for tumour growth, expansion, formation of bone lesions and potentially
also activation of disseminated tumour cells, leading to bone relapses. We review
the current knowledge of bone targeted therapies in advanced breast cancer, with
a focus on new insights into their bone-preserving and antitumor activity.
Current guidelines, pathology of bone metastasis, mode of action and common side
effects have been summarised. We also elaborate on the use of bisphosphonates and
denosumab in early breast cancer, during adjuvant therapy with aromatase
inhibitors.
PMID- 28695564
TI - Iron supplementation in Switzerland - A bi-national, descriptive and
observational study.
AB - BACKGROUND: Iron deficiency is the most common nutritional disorder in the world,
and it is the only common nutrient deficiency in industrialised nations. It is
thought to be the most common cause of anaemia. Use of iron supplementation in
Switzerland has not been previously quantified in detail. OBJECTIVES: We
quantified use of iron supplementation from Swiss data and compared it with data
from the UK. We assessed the frequency of serum ferritin and haemoglobin tests
prior to newly started iron therapy to see whether use was based on documented
low iron levels or blood parameters, especially in the case of parenteral iron
supplementation. METHODS: We conducted a retrospective descriptive study of
prescription iron supplementation use, and compared use of oral or parenteral
iron drugs between Switzerland (CH) and the UK. We retrieved Swiss data from the
Swiss Health Insurance Helsana Group, and UK data were from the Clinical Practice
Research Datalink (CPRD). The study period was 2012 to 2014. RESULTS: The 3-year
prevalence of iron supplementation was 9.4% in Switzerland and 4.4% in the UK.
Iron use increased slightly between 2012 and 2014 in both countries (CH +0.3%, UK
+0.2%). Recorded parenteral iron administration was roughly a thousand times
higher in Switzerland (1.9%) than in the UK in 2014. In Switzerland, iron
supplements were mostly given to patients aged 20 to 49 years or older than of 80
years. In the UK, iron supplementation was less frequent in younger people, but
more prevalent in the elderly. Prior to a first iron prescription, ferritin tests
were done more frequently in Switzerland (oral 67.2%, parenteral 86.6%) than in
the UK (oral 43.3%, parenteral 65.5%). Haemoglobin was measured before a new
parenteral iron therapy rarely in Switzerland (oral 14.9%, parenteral 11.7%), but
frequently in the UK (oral 77.4%, parenteral 85.6%). CONCLUSIONS: Iron
supplementation is more common in Switzerland than in the UK, particularly
parenteral iron supplementation. Haemoglobin measurements prior to a new
parenteral iron therapy are relatively infrequent in Switzerland despite the
required documentation of haemoglobin prior to therapy.
PMID- 28695565
TI - Dental patch testing in patients with undifferentiated oral lichen planus.
AB - BACKGROUND/OBJECTIVES: Distinguishing between oral lichen planus (LP) and
lichenoid reactions to dental restorations can be impossible on clinical and
histopathological grounds. Epicutaneous patch testing is an investigation that
may guide patients and physicians in making timely and costly decisions to
replace or cover existing dental restorations. This study aimed to assess the
role of epicutaneous patch testing with a battery of dental allergens in patients
with undifferentiated oral LP. METHODS: A retrospective review of the medical
records of patients with biopsy-proven oral LP referred by an oral medicine
specialist and who presented for dental epicutaneous patch testing at a
dermatology clinic in Perth, Western Australia between 2009 and 2016 was
performed. RESULTS: In total, 68 patients were included, of whom 54 (79%) had
positive patch tests. Gold 26 (48%), mercury 24 (44%), nickel 22 (41%), copper 19
(35%), potassium dichromate 14 (26%) and methylhydroquinone 13 (24%) were the
most common allergens for which patients tested positive. Hypothyroidism and non
steroidal anti-inflammatory drugs were associated with negative patch tests (P =
0.01 and 0.04, respectively). Smoking history, other medications and
comorbidities, the location of the dental restorations and unilateral or
bilateral disease were not significantly associated with the patch test results.
Restorations were removed in 23 patients: 21 of these (91%) had positive
epicutaneous patch tests. Of the 20 patients followed up, 19 (95%) experienced
some improvement, among whom 11 (58%) had complete remission. CONCLUSION:
Epicutaneous patch testing disclosed a high proportion of relevant positives.
This guided the clinical decision to change dental restorations, with high rate
of clinical improvement.
PMID- 28695566
TI - Portal vein territory identification using indocyanine green fluorescence
imaging: Technical details and short-term outcomes.
AB - BACKGROUND AND OBJECTIVES: Portal vein (PV) territory identification during liver
resection may be performed using indocyanine green (ICG) fluorescence imaging
technique. However, the technical details of the fluorescence staining technique
have not been fully elucidated. This study was performed to demonstrate the
technical details of PV territory identification using fluorescence imaging and
evaluates the short-term outcomes. METHODS: From 2011 to 2015, 105 underwent
liver resection at the University of Tokyo Hospital with one of the following
fluorescence staining techniques by transhepatic PV injection or intravenous
injection of ICG: single staining (n = 36), multiple staining (n = 31),
counterstaining (n = 22), negative staining (n = 13), or paradoxical negative
staining (n = 3). RESULTS: The PV territory was identified as a region with
fluorescence or a defect of fluorescence using one of the five staining
techniques. ICG was administered by transhepatic PV injection in all but the
negative staining technique, which employed intravenous injection. No adverse
events associated with the ICG administration occurred. The mortality,
postoperative total morbidity, and the major complication (Clavien-Dindo grade
>=III) rates were 0.0%, 14.3%, and 7.6%. CONCLUSIONS: We have demonstrated the
technical details of five types of fluorescence staining techniques. These
techniques are safe to perform and facilitate clear visualization of the PV
territory in real time, enhancing the efficacy of anatomical removal of such
territories.
PMID- 28695567
TI - Tc-99m tilmanocept versus Tc-99m sulfur colloid in breast cancer sentinel lymph
node identification: Results from a randomized, blinded clinical trial.
AB - INTRODUCTION: No prior trials have compared sentinel lymph node (SLN)
identification outcomes between Tc-99m tilmanocept (TcTM) and Tc-99m sulfur
colloid (TcSC) in breast cancer (BC). METHODS: We report on the secondary
outcomes from a randomized, double-blinded, single surgeon clinical trial
comparing post-injection site pain between TcTM and TcSC. Patients were
randomized to receive a preoperative single, peritumoral intradermal injection of
TcTM or TcSC. The number of total, "hot", and blue nodes detected and removed
were compared between groups. RESULTS: Fifty-two (27-TcSC and 25-TcTM) patients
were enrolled and underwent definitive surgical treatment. At least one "hot" SLN
was detected in all patients. Three (5.8%) patients had a disease positive-SLN.
The total number of SLNs removed was 61 (mean 2.26 (standard deviation (SD)
0.90)) in the TcSC group and 54 (mean 2.16 (SD 0.90)) in the TcTM group, P =
0.69. The total number of "hot" nodes in the TcSC group was 1.96 (SD 0.76)
compared to 2.04 (SD 0.73) in the TcTM group, P = 0.71. CONCLUSIONS: The number
of identified SLNs did not differ significantly between TcTM and TcSC. Given that
no significant technical advantages exist between the two agents, surgeons should
choose a radiopharmaceutical based on cost and side effect profile.
PMID- 28695568
TI - PRMT1 regulates astrocytic differentiation of embryonic neural stem/precursor
cells.
AB - Arginine methylation is a post-translational modification which is catalyzed by
protein arginine methyltransferases (PRMTs). Here, we report that PRMT1 is highly
expressed in neural stem/precursor cells (NS/PCs) of mouse embryos, and knockdown
of PRMT1 in NS/PCs suppresses the generation of astrocytes. The luciferase assay
demonstrated that knockdown of PRMT1 inhibits activation of the promoter of a
typical astrocytic marker gene, glial fibrillary acidic protein (Gfap), in
NS/PCs. The transcription factor signal transducer and activator of transcription
3 (STAT3) is known to generally be critical for astrocytic differentiation of
NS/PCs. We found that PRMT1 methylates arginine residue(s) of STAT3 to regulate
its activity positively, resulting in the promotion of astrocytic differentiation
of NS/PCs.
PMID- 28695569
TI - In vitro evidence for the participation of Drosophila melanogaster sperm beta-N
acetylglucosaminidases in the interactions with glycans carrying terminal N
acetylglucosamine residues on the egg's envelopes.
AB - Fertilization is a complex and multiphasic process, consisting of several steps,
where egg-coating envelope's glycoproteins and sperm surface receptors play a
critical role. Sperm-associated beta-N-acetylglucosaminidases, also known as
hexosaminidases, have been identified in a variety of organisms. Previously, two
isoforms of hexosaminidases, named here DmHEXA and DmHEXB, were found as
intrinsic proteins in the sperm plasma membrane of Drosophila melanogaster. In
the present work, we carried out different approaches using solid-phase assays in
order to analyze the oligosaccharide recognition ability of D. melanogaster sperm
hexosaminidases to interact with well-defined carbohydrate chains that might
functionally mimic egg glycoconjugates. Our results showed that Drosophila
hexosaminidases prefer glycans carrying terminal beta-N-acetylglucosamine, but
not core beta-N-acetylglucosamine residues. The capacity of sperm beta-N
acetylhexosaminidases to bind micropylar chorion and vitelline envelope was
examined in vitro assays. Binding was completely blocked when beta-N
acetylhexosaminidases were preincubated with the glycoproteins ovalbumin and
transferrin, and the monosaccharide beta-N-acetylglucosamine. Overall, these data
support the hypothesis of the potential role of these glycosidases in sperm-egg
interactions in Drosophila.
PMID- 28695571
TI - Australian lobbyist registers are not serving the purposes they were designed
for.
AB - INTRODUCTION AND AIMS: There is widespread concern about the nature, extent and
impacts of lobbying by industries selling unhealthy commodities, which threatens
public health and undermines important democratic processes. In the last decade,
all Australian jurisdictions (except the Northern Territory) have established
lobbyist registers with the stated objective of increasing the capacity of
government and the public to scrutinise lobbying. Our aim was to assess whether
the registers are fulfilling this objective. DESIGN AND METHODS: We conducted web
searches of registers in Australian jurisdictions in 2014 and 2015 to determine
what type of information they collected and whether data were accessible. We
supplemented searches with e-mails and phone calls to registrars to clarify
policies and seek additional information. RESULTS: We found that the data were
lacking in critical details and historical information was difficult or
impossible to obtain. None of the registers required in-house lobbyists to
register or to be bound by the Lobbying Codes of Conduct. None required that
informal lobbying (e.g. by government relations staff within a company) be
recorded, and none provided detailed information about the nature and extent of
lobbying activities. DISCUSSION AND CONCLUSIONS: The registers do not meet the
stated objective of making lobbying activity transparent to the Australian
public. Timely access to comprehensive information is essential to help promote
the rational development of policy concerning tobacco, alcohol and gambling
problems. There is an urgent need to reform lobbyist registers to ensure that
they are comprehensive and transparent.
PMID- 28695570
TI - Population pharmacokinetics and electrocardiographic effects of
dihydroartemisinin-piperaquine in healthy volunteers.
AB - AIMS: The aims of the present study were to evaluate the pharmacokinetic
properties of dihydroartemisinin (DHA) and piperaquine, potential drug-drug
interactions with concomitant primaquine treatment, and piperaquine effects on
the electrocardiogram in healthy volunteers. METHODS: The population
pharmacokinetic properties of DHA and piperaquine were assessed in 16 healthy
Thai adults using an open-label, randomized, crossover study. Drug concentration
time data and electrocardiographic measurements were evaluated with nonlinear
mixed-effects modelling. RESULTS: The developed models described DHA and
piperaquine population pharmacokinetics accurately. Concomitant treatment with
primaquine did not affect the pharmacokinetic properties of DHA or piperaquine. A
linear pharmacokinetic-pharmacodynamic model described satisfactorily the
relationship between the individually corrected QT intervals and piperaquine
concentrations; the population mean QT interval increased by 4.17 ms per 100 ng
ml-1 increase in piperaquine plasma concentration. Simulations from the final
model showed that monthly and bimonthly mass drug administration in healthy
subjects would result in median maximum QT interval prolongations of 18.9 ms and
16.8 ms, respectively, and would be very unlikely to result in prolongation of
more than 50 ms. A single low dose of primaquine can be added safely to the
existing DHA-piperaquine treatment in areas of multiresistant Plasmodium
falciparum malaria. CONCLUSIONS: Pharmacokinetic-pharmacodynamic modelling and
simulation in healthy adult volunteers suggested that therapeutic doses of DHA
piperaquine in the prevention or treatment of P. falciparum malaria are unlikely
to be associated with dangerous QT prolongation.
PMID- 28695572
TI - Isomer Selectivity in Low-Energy Electron Attachment to Nitroimidazoles.
AB - Low-energy electrons effectively decompose the isomers 2-nitroimidazole and 4(5)
nitroimidazole by dissociative electron attachment (DEA) into a variety of
fragment anions and radicals. The present study shows that a distinct selectivity
for the two isomers occurs in the DEA reactions. Several new decay channels are
observed for 2-nitroimidazole, including a dominant one leading to the loss of
molecular H2 O by attachment of a low-energy electron. In contrast, the loss of a
single hydrogen atom is a much more efficient reaction in DEA to 4(5)
nitroimidazole. Quantum chemical calculations were carried out to explain the
pronounced isomer effect found in the DEA experiment. Although the free energies
of the reactions are similar for the different isomers, the very different
natures of the dipole-bound states and valence-bound anions lead to preference
for or hindrance of a particular dissociation channel. Nitroimidazolic compounds
are considered as radiosensitizing compounds in tumor radiation therapy. The
enhanced formation of fragments, including the highly reactive hydroxyl radical,
in DEA to 2-nitroimidazole suggests that it may be a more efficient
radiosensitizing agent than 4(5)-nitroimidazoles.
PMID- 28695573
TI - Relationships Between Self-Reported and Observed Parenting Behaviour, Adolescent
Disordered Eating Attitudes and Behaviours, and the 5-HTTLPR Polymorphism: Data
From the Australian Temperament Project.
AB - This study examined whether self-reported and observationally measured parental
behaviours were associated with disordered eating, and investigated possible
moderation by a serotonin-transporter polymorphism (5-HTTLPR). Study 1 included
650 adolescents from the Australian Temperament Project who completed the Eating
Disorder Inventory-2 Drive for Thinness and Bulimia scales at 15/16 years and
were genotyped for 5-HTTLPR. Parents completed an Australian Temperament Project
devised measure of parental warmth and harsh punishment. Study 2 included a
subgroup of 304 participants who also engaged in a video-recorded family
interaction, with observed parental warmth and hostility coded by the Iowa Family
Interaction Rating Scale. Greater self-reported parental warmth was associated
with lower bulimia scores. Conversely, observationally measured parental warmth
was associated with lower drive for thinness, but not bulimia. Self-reported
parental harsh punishment was associated with bulimia only, with observed
parental hostility associated with neither outcome. 5-HTTLPR genotype did not
moderate the relationship between parent behaviours and adolescent disordered
eating. Copyright (c) 2017 John Wiley & Sons, Ltd and Eating Disorders
Association.
PMID- 28695574
TI - Alternative male mating tactics of the endemic Red Sea parrotfish Scarus
ferrugineus.
AB - The present study shows that small non-territorial terminal-phase males of the
rusty parrotfish Scarus ferrugineus are reproductively active and are comparable
with initial-phase males in behaviour, rates of participation during group
spawning and success in streaking into pair spawning. Large territorial terminal
phase males defend contiguous territories for several hours during the morning
where they pair spawn with initial-phase females.
PMID- 28695575
TI - Combining the sick lobe theory with markers of field cancerization for refinement
of a personalized surgical margin.
PMID- 28695576
TI - Mechanical Ventilation and Extracorporeal Membrane Oxygenation as a Bridging
Strategy to Lung Transplantation: Significant Gains in Survival.
AB - Mechanical ventilation (MV) and extracorporeal membrane oxygenation (ECMO) are
increasingly used to bridge patients to lung transplantation. We investigated the
impact of using MV, with or without ECMO, before lung transplantation on survival
after transplantation by performing a retrospective analysis of 826 patients who
underwent transplantation at our high-volume center. Recipient characteristics
and posttransplant outcomes were analyzed. Most lung transplant recipients (729
patients) did not require bridging; 194 of these patients were propensity matched
with patients who were bridged using MV alone (48 patients) or MV and ECMO (49
patients). There was no difference in overall survival between the MV and MV+ECMO
groups (p = 0.07). The MV+ECMO group had significantly higher survival
conditioned on surviving to 1 year (median 1,811 days ([MV] vs. not reached
([MV+ECMO], p = 0.01). Recipients in the MV+ECMO group, however, were more likely
to require ECMO after lung transplantation (16.7% MV vs. 57.1% MV+ECMO, p <
0.001). There were no differences in duration of postoperative MV, hospital stay,
graft survival, or the incidence of acute rejection, renal failure, bleeding
requiring reoperation, or airway complications. In this contemporary series, the
combination of MV and ECMO was a viable bridging strategy to lung transplantation
that led to acceptable patient outcomes.
PMID- 28695577
TI - Prediction of benefit after transarterial chemoembolization (TACE):
Subclassifications or scoring systems?
PMID- 28695578
TI - Authors' reply to Dr. Bailey's commentary: Predicting clinical relevance of
grapefruit-drug interactions: A complicated process.
PMID- 28695579
TI - Exploring the evidence base for Tier 3 weight management interventions for
adults: a systematic review.
AB - Specialist weight management services provide a treatment option for severe
obesity. The objective of the study is to review the characteristics, impact and
practice implications of specialist weight management services for adults in the
UK. Systematic review: EMBASE, MEDLINE and PsycINFO were searched from January
2005 to March 2016 with supplementary searches. Adults with a body mass index of
>=40 kg m-2 , or >=35 kg m-2 with comorbidity or >=30 kg m-2 with type 2 diabetes
and any study of multicomponent interventions, in any UK or Ireland setting,
delivered by a specialist multidisciplinary team are the inclusion criteria.
Fourteen studies in a variety of settings were included: 1 randomized controlled
trial, 3 controlled and 10 observational studies. Mean baseline body mass index
and age ranged from 40 to 54 kg m-2 and from 40 to 58 years. The studies were
heterogeneous making comparisons of service characteristics difficult.
Multidisciplinary team composition and eligibility criteria varied; dropout rates
were high (43-62%). Statistically significant reduction in mean body mass index
over time ranged from -1.4 to -3.1 kg m-2 and mean weight changes ranged from
2.2 to -12.4 kg. Completers achieving at least 5% reduction of initial body
weight ranged from 32 to 51%. There was evidence for improved outcomes in
diabetics. Specialist weight management services can demonstrate clinically
significant weight loss and have an important role in supporting adults to manage
severe and often complex forms of obesity. This review highlights important
variations in provision and strongly indicates the need for further research into
effective approaches to support severely obese adults.
PMID- 28695580
TI - Synthesis and Configuration of Neomaclafungin A.
AB - The relative and absolute configuration of neomaclafungins were impossible to
establish by spectroscopic analyses alone because of the lack of exploitable 1 H
1 H couplings and nOes between the upper and the lower subunits. This very
difficult task now is finally completed by an enantioselective total synthesis of
neomaclafungin A (revised) and its diastereomer (reported). The results also
provided a key reference for the complete structures for other neomaclafungins
and the long-known closely related natural product maclafungin.
PMID- 28695581
TI - Trophic redundancy among fishes in an East African nearshore seagrass community
inferred from stable-isotope analysis.
AB - Stable-isotope analysis supplemented with stomach contents data from published
sources was used to quantify the trophic niches, trophic niche overlaps and
potential trophic redundancy for the most commonly caught fish species from an
East African nearshore seagrass community. This assessment is an important first
step in quantifying food-web structure in a region subject to intense fishing
activities. Nearshore food webs were driven by at least two isotopically distinct
trophic pathways, algal and seagrass, with a greater proportion of the sampled
species feeding within the seagrass food web (57%) compared with the algal food
web (33%). There was considerable isotopic niche overlap among species (92% of
species overlapped with at least one other species). Narrow isotopic niche widths
of most (83%) species sampled, low isotopic similarity (only 23% of species
exhibited no differences in delta13 C and delta15 N) and low predicted trophic
redundancy among fishes most commonly caught by fishermen (15%), however, suggest
that adjustments to resource management concerning harvesting and gear
selectivity may be needed for the persistence of artisanal fishing in northern
Tanzania. More detailed trophic studies paired with information on spatio
temporal variation in fish abundance, especially for heavily targeted species,
will assist in the development and implementation of management strategies to
maintain coastal food-web integrity.
PMID- 28695582
TI - A joint logistic regression and covariate-adjusted continuous-time Markov chain
model.
AB - The use of longitudinal measurements to predict a categorical outcome is an
increasingly common goal in research studies. Joint models are commonly used to
describe two or more models simultaneously by considering the correlated nature
of their outcomes and the random error present in the longitudinal measurements.
However, there is limited research on joint models with longitudinal predictors
and categorical cross-sectional outcomes. Perhaps the most challenging task is
how to model the longitudinal predictor process such that it represents the true
biological mechanism that dictates the association with the categorical response.
We propose a joint logistic regression and Markov chain model to describe a
binary cross-sectional response, where the unobserved transition rates of a two
state continuous-time Markov chain are included as covariates. We use the method
of maximum likelihood to estimate the parameters of our model. In a simulation
study, coverage probabilities of about 95%, standard deviations close to standard
errors, and low biases for the parameter values show that our estimation method
is adequate. We apply the proposed joint model to a dataset of patients with
traumatic brain injury to describe and predict a 6-month outcome based on
physiological data collected post-injury and admission characteristics. Our
analysis indicates that the information provided by physiological changes over
time may help improve prediction of long-term functional status of these severely
ill subjects. Copyright (c) 2017 John Wiley & Sons, Ltd.
PMID- 28695583
TI - Quantitative 13 C-isotope labelling-based analysis to elucidate the influence of
environmental parameters on the production of fermentative aromas during wine
fermentation.
AB - Nitrogen and lipids are key nutrients of grape must that influence the production
of fermentative aromas by wine yeast, and we have previously shown that a strong
interaction exists between these two nutrients. However, more than 90% of the
acids and higher alcohols (and their acetate ester derivatives) were derived from
intermediates produced by the carbon central metabolism (CCM). The objective of
this study was to determine how variations in nitrogen and lipid resources can
modulate the contribution of nitrogen and carbon metabolisms for the production
of fermentative aromas. A quantitative analysis of metabolism using 13 C-labelled
leucine and valine showed that nitrogen availability affected the part of the
catabolism of N-containing compounds, the formation of alpha-ketoacids from CCM
and the redistribution of fluxes around these precursors, explaining the optimum
production of higher alcohols occurring at an intermediate nitrogen content.
Moreover, nitrogen content modulated the total production of acids and higher
alcohols differently, through variations in the redox state of cells. We also
demonstrated that the phytosterol content, modifying the intracellular
availability of acetyl-CoA, can influence the flux distribution, especially the
formation of higher alcohols and the conversion of alpha-ketoisovalerate to alpha
ketoisocaproate.
PMID- 28695584
TI - Patient-controlled analgesia with remifentanil vs. alternative parenteral methods
for pain management in labour: a Cochrane systematic review.
AB - We aimed to assess the effectiveness of remifentanil used as intravenous patient
controlled analgesia for the pain of labour. We performed a systematic literature
search in December 2015 (updated in December 2016). We included randomised,
controlled and cluster-randomised trials of women in labour with planned vaginal
delivery receiving patient-controlled remifentanil compared principally with
other parenteral and patient-controlled opioids, epidural analgesia and
continuous remifentanil infusion or placebo. The primary outcomes were patient
satisfaction with pain relief and the occurrence of adverse events for mothers
and newborns. We assessed risk of bias for each included study and applied the
GRADE approach for the quality of evidence. We included total zero event trials,
using a constant continuity correction of 0.01 and a random-effect meta-analysis.
Twenty studies were included in the qualitative analysis; within these, 3713
participants were randomised and 3569 analysed. Most of our pre-specified
outcomes were not studied in the included trials. However, we found evidence that
women using patient-controlled remifentanil were more satisfied with pain relief
than women receiving parenteral opioids (four trials, 216 patients, very low
quality evidence) with a standardised mean difference ([SMD] 95%CI) of 2.11 (0.72
3.49), but were less satisfied than women receiving epidural analgesia (seven
trials, 2135 patients, very low quality evidence), -0.22 (-0.40 to -0.04). Data
on adverse events were sparse. However, the relative risk (95%CI) for maternal
respiratory depression for patient-controlled remifentanil compared with epidural
analgesia (three trials, 687 patients, low-quality evidence) was 0.91 (0.51
1.62). Compared with continuous intravenous infusion of remifentanil (two trials,
135 patients, low-quality evidence) no conclusion could be reached as all study
arms showed zero events. The relative risk (95%CI) of Apgar scores less than 7 at
5 min after birth compared with epidural analgesia (five trials, 1322
participants, low-quality evidence) was 1.26 (0.62-2.57).
PMID- 28695585
TI - THRIVE and airway fires.
PMID- 28695587
TI - SB4YB and the role of industry in patient safety.
PMID- 28695586
TI - Intra-operative protective mechanical ventilation in lung transplantation: a
randomised, controlled trial.
AB - Primary graft dysfunction occurs in up to 25% of patients after lung
transplantation. Contributing factors include ventilator-induced lung injury,
cardiopulmonary bypass, ischaemia-reperfusion injury and excessive fluid
administration. We evaluated the feasibility, safety and efficacy of an open-lung
protective ventilation strategy aimed at reducing ventilator-induced lung injury.
We enrolled adult patients scheduled to undergo bilateral sequential lung
transplantation, and randomly assigned them to either a control group (volume
controlled ventilation with 5 cmH2 O, positive end-expiratory pressure, low tidal
volumes (two-lung ventilation 6 ml.kg-1 , one-lung ventilation 4 ml.kg-1 )) or an
alveolar recruitment group (regular step-wise positive end-expiratory pressure
based alveolar recruitment manoeuvres, pressure-controlled ventilation set at 16
cmH2 O with 10 cmH2 O positive end-expiratory pressure). Ventilation strategies
were commenced from reperfusion of the first lung allograft and continued for the
duration of surgery. Regular PaO2 /FI O2 ratios were calculated and venous blood
samples collected for inflammatory marker evaluation during the procedure and for
the first 24 h of intensive care stay. The primary end-point was the PaO2 /FI O2
ratio at 24 h after first lung reperfusion. Thirty adult patients were studied.
The primary outcome was not different between groups (mean (SD) PaO2 /FI O2 ratio
control group 340 (111) vs. alveolar recruitment group 404 (153); adjusted p =
0.26). Patients in the control group had poorer mean (SD) PaO2 /FI O2 ratios at
the end of the surgical procedure and a longer median (IQR [range]) time to
tracheal extubation compared with the alveolar recruitment group (308 (144) vs.
402 (154) (p = 0.03) and 18 (10-27 [5-468]) h vs. 15 (11-36 [5-115]) h (p =
0.01), respectively). An open-lung protective ventilation strategy during surgery
for lung transplantation is feasible, safe and achieves favourable ventilation
parameters.
PMID- 28695588
TI - THRIVE and pre-oxygenation.
PMID- 28695589
TI - THRIVE, rapid sequence induction and oxygenation.
PMID- 28695591
TI - Auditory stimulation and levels of anaesthesia.
PMID- 28695590
TI - Airway assessment/management paradigm - does a spectral or a binary approach fit
better? A reply.
PMID- 28695592
TI - Cognitive aids, checklists and mental models - a reply.
PMID- 28695593
TI - Pre-hospital pre-oxygenation strategies.
PMID- 28695594
TI - Problematic use of a Pentax AWS-S200 in emergency and disaster medicine.
PMID- 28695595
TI - Optimising Glidescope performance.
PMID- 28695596
TI - Regression: How much data do I really need?
PMID- 28695597
TI - GE Healthcare Carestation 650 carbon dioxide canister design fault.
PMID- 28695598
TI - THRIVE, rapid sequence induction and oxygenation. A reply.
PMID- 28695599
TI - Two further episodes of a defective Optima CLX laryngoscope blade.
PMID- 28695600
TI - Cognitive aids, checklists and mental models.
PMID- 28695601
TI - Pre-hospital pre-oxygenation strategies: a reply.
PMID- 28695603
TI - GE Healthcare Carestation 650 carbon dioxide canister design fault -
manufacturer's reply.
PMID- 28695602
TI - Airway assessment/management paradigm - does a spectral or a binary approach fit
better?
PMID- 28695604
TI - THRIVE, rapid sequence induction and accidental awareness.
PMID- 28695605
TI - Returns to scientific publications for pharmaceutical products in the United
States.
AB - Drug-specific clinical and health economic and outcomes research (HEOR)
publications have amassed, but their effect on drug sales is largely unknown. We
estimated the impact of publications on pharmaceutical sales in 3 markets
(statins, rheumatoid arthritis, and asthma drugs) with varying generic
competition. An event-study approach with fixed effects and difference-in-fixed
effects modeling was used to estimate the causal effects of drug-specific
publications on subsequent quarter's drug-specific sales and volume. High-impact
clinical and HEOR publications have significant positive effects on sales
(mediated through price) and volume in the statin market (high generic
competition). High-impact clinical publications have a significant positive
effect on sales (mediated through volume) in low-generic competition market
(asthma). The effects of publications in the rheumatoid arthritis market (no
generic competition) on sales were null. Manufacturers' investment in clinical
and HEOR publications needs to be strategic and should be anticipated and
complemented by public investments in such studies.
PMID- 28695606
TI - Orally administered Chrysin improves post-thawed sperm quality and fertility of
rooster.
AB - Chrysin is a bioflavonoid compound found in passion flower, chamomile, propolis
and honey at high levels. Post-thawed sperm quality and fertility of Chrysin-fed
roosters were assessed in this study. Twenty 40-week-old male broiler breeders
were randomly divided into four groups and fed basal diet supplemented with
different levels of Chrysin including 0 (Ch-0), 25 (Ch-25), 50 (Ch-50) or 75 (Ch
75) mg/day for 12 consecutive weeks. Semen samples were weekly collected from 6th
to 9th week of experiment to evaluate some sperm quality parameters including
total and progressive motility, plasma membrane integrity and functionality (in
fresh and post-thawed samples) and mitochondrial activity (only in post-thawed
samples). Also, collected semen samples from 10th, 11th and 12th week of
experiment were frozen and then artificially inseminated to test fertility rate.
According to the results, an improvement in both fresh and post-thawed sperm
quality including total [fresh: 88.00 +/- 0.58 and 87.25 +/- 0.67 (p < .01); post
thawed: 51.07 +/- 2.05 and 52.72 +/- 1.96 (p < .01)] and progressive motility
[fresh: 76.00 +/- 0.58 and 78.25 +/- 0.65 (p < .01); post-thawed: 40.61 +/- 2.01
and 39.88 +/- 2.01 (p < .01)], plasma membrane integrity [fresh: 91.60 +/- 0.58
and 89.85 +/- 0.59 (p < .01); post-thawed: 56.99 +/- 1.86 and 54.39 +/- 1.86 (p <
.01)] and functionality [fresh: 75.40 +/- 0.42 and 77.90 +/- 0.96 (p < .01); post
thawed: 45.69 +/- 1.71 and 46.35 +/- 1.71 (p < .01)] was noted for both Ch-50 and
Ch-75, respectively, groups compared to control group. Despite no significant
change in mitochondrial activity, fertility rate of post-thawed spermatozoa was
significantly improved in all Chrysin-fed groups compared to Ch-0 group. In
conclusion, oral Chrysin administration to roosters could ameliorate
cryopreservation-induced impairment of sperm quality and fertility rate.
PMID- 28695607
TI - Visualization of the tentorial innervation of human dura mater.
AB - Posterior projections of the ophthalmic division of the trigeminal nerve (the
ophthalmic nerve) are distributed in the tentorium cerebelli as recurrent
meningeal branches. We investigated the morphological tentorial distribution of
the ophthalmic nerve. Fifty-two sides of the tentorium cerebelli and adjacent
dura mater obtained from 29 human specimens were stained using Sihler's method to
examine the nerve fibres in the dural sheets. The innervation patterns of the
tentorium cerebelli were classified into the following four types according to
their distributions: Type 1, where nerve fibres projected to both the straight
and transverse sinuses; Type 2, where nerve fibres projected only to the
transverse sinus and lateral convexity; Type 3, where nerve fibres projected
medially only to the straight sinus and the posterior part of the falx cerebri;
and Type 4, where the nerve fibres terminated within the tentorium cerebelli.
Images of the tentorium cerebelli were superimposed to identify areas of dense
innervation. The incidence rates of Types 1-4 were 71.2% (n = 37), 21.2% (n =
11), 3.8% (n = 2) and 3.8% (n = 2), respectively. More branches of nerve fibres
traversed towards the transverse sinus posterolaterally than towards the straight
sinus medially. The space between the anterior half of the straight sinus and the
medial tentorial notch can be considered a safe surgical area where innervation
is scarce. The posterior part of the falx cerebri was innervated by the
ophthalmic nerve that traversed to the straight sinus. The parietal branches of
the middle meningeal artery in the lateral convexity that were projected
orthogonally by the ophthalmic nerve traversed the transverse sinus, implicating
their vulnerability and possible sensitivity under physiological or neurosurgical
conditions. This study has revealed the macroscopic tentorial innervation of the
dura mater in humans, which could be useful information for both neurosurgeons
and neurologists.
PMID- 28695608
TI - Integration of 'sick lobe hypothesis' with concept of field cancerisation for a
personalised surgical margin for breast conserving surgery.
PMID- 28695609
TI - Pharmaco-parasitological evaluation of the ricobendazole plus levamisole
nematodicidal combination in cattle.
AB - The goals of the current study were to evaluate the potential pharmacokinetic
(PK) interactions and the clinical efficacy occurring after the subcutaneous
(s.c.) administration of ricobendazole (RBZ) and levamisole (LEV) given both
separately and co-administered to calves naturally infected with susceptible
gastrointestinal nematodes. The clinical efficacy was shown in two seasons,
winter and spring, with predominance of different nematode populations. Groups of
15 calves were treated with RBZ alone, LEV alone and RBZ + LEV combination, and
an untreated group was kept as a Control. RBZ and LEV plasma concentrations were
quantified by HPLC. The clinical efficacy was determined by the faecal egg count
reduction test. RBZ and LEV have similar plasma persistence, being detected in
plasma over 24 hr post-treatment. No PK interactions were observed after the
combined treatment, with similar PK parameters (p > .05) obtained for the single
drug and the combination-based strategy. In winter, the observed clinical
efficacies were 96%, 99% and 100% for groups treated with RBZ, LEV and RBZ + LEV,
respectively; however, in spring, the efficacies were 95%, 93% and 96% for the
same groups. Remarkably, the combination was the only treatment that achieved
100% clinical efficacy against both Haemonchus spp and Ostertagia spp in winter;
but the increased presence of Ostertagia spp. in spring (28% in untreated group)
determined a tendency to reduced efficacies compared to winter time (only 10% of
Ostertagia spp. in untreated group), even for the combined treatment. Overall, in
a scenario where the nematode population is susceptible, the RBZ + LEV treatment
may be a valid combination in cattle to delay the development of resistance,
especially in winter when this combination achieved 100% of efficacy. Thus,
selection of anthelmintic resistance will never occur. In fact, this is one of
the greatest challenges for the whole cattle production system: to be one step
ahead of anthelmintic resistance.
PMID- 28695610
TI - Anion gap can differentiate between psychogenic and epileptic seizures in the
emergency setting.
AB - Differentiation between psychogenic nonepileptic seizures (PNES) and generalized
convulsive epileptic seizures (ES) is important for appropriate triaging in the
emergency department (ED). This can be difficult in the ED, as the event is often
not witnessed by a medical professional. In the current study, we investigated
whether anion gap (AG), bicarbonate, and the Denver Seizure Score (DSS) could
differentiate between PNES and ES. Of a total of 1,354 subjects reviewed from a
tertiary care medical center, 27 PNES and 27 ES patients were identified based on
clinical description and subsequent electroencephalogram. Multivariate logistic
regression analysis and receiver operating characteristic curves were used to
determine whether there was an association between seizure type and AG,
bicarbonate, or DSS (24-bicarbonate + 2 * [AG-12]) when samples were drawn within
24 h of the concerning event. The result showed that sensitivity and negative
predictive value dropped markedly for all measures if samples were drawn >2 h
after the event; the sensitivity was similar for AG and DSS and higher than for
bicarbonate. We propose that AG > 10 (sensitivity of 81.8%, specificity of 100%)
in the first 2 h after the event could be used as a potential tool in the ED to
help differentiate between PNES and ES.
PMID- 28695612
TI - A revised model for coping with advanced cancer. Mapping concepts from a
longitudinal qualitative study of patients and carers coping with advanced cancer
onto Folkman and Greer's theoretical model of appraisal and coping.
AB - OBJECTIVE: To explore whether the Folkman and Greer theoretical model of
appraisal and coping reflects the processes used by people living with advanced
cancer. METHODS: Interview data from a longitudinal qualitative study with people
with advanced (stage 3 or 4) cancer (n = 26) were mapped onto the concepts of the
Folkman and Greer theoretical model. Qualitative interviews conducted in home
settings, 4-12 weeks apart (n = 45) examined coping strategies, why people
thought they were effective, and in what circumstances. Interviews were coded and
analysed using techniques of constant comparison. RESULTS: Mapping coping
strategies clearly onto the problem- or emotion-focused elements of the model
proved problematic. Fluctuating symptoms, deterioration over time, and uncertain
timescales in advanced cancer produce multiple events simultaneously or in quick
succession. This demands not only coping with a single event but also frequent
repositioning, often to an earlier point in the coping process. In addition,
there is substantial ongoing potential for some degree of distress rather than
purely "positive emotion" as the final stage in the process is death with several
points of permanent loss of capability in the interim. CONCLUSIONS: The Folkman
and Greer theoretical model is helpful in deconstructing the discrete "problem
focused" or "emotion-focused" coping mechanisms participants describe, but its
formulation as a linear process with a single, positive, outcome is
insufficiently flexible to capture the evolution of coping for people with
advanced cancer.
PMID- 28695611
TI - Prediction of type 1 diabetes using a genetic risk model in the Diabetes
Autoimmunity Study in the Young.
AB - BACKGROUND: Genetic predisposition for type 1 diabetes (T1D) is largely
determined by human leukocyte antigen (HLA) genes; however, over 50 other genetic
regions confer susceptibility. We evaluated a previously reported 10-factor
weighted model derived from the Type 1 Diabetes Genetics Consortium to predict
the development of diabetes in the Diabetes Autoimmunity Study in the Young
(DAISY) prospective cohort. Performance of the model, derived from individuals
with first-degree relatives (FDR) with T1D, was evaluated in DAISY general
population (GP) participants as well as FDR subjects. METHODS: The 10-factor
weighted risk model (HLA, PTPN22 , INS , IL2RA , ERBB3 , ORMDL3 , BACH2 , IL27 ,
GLIS3 , RNLS ), 3-factor model (HLA, PTPN22, INS ), and HLA alone were compared
for the prediction of diabetes in children with complete SNP data (n = 1941).
RESULTS: Stratification by risk score significantly predicted progression to
diabetes by Kaplan-Meier analysis (GP: P = .00006; FDR: P = .0022). The 10-factor
model performed better in discriminating diabetes outcome than HLA alone (GP, P =
.03; FDR, P = .01). In GP, the restricted 3-factor model was superior to HLA (P =
.03), but not different from the 10-factor model (P = .22). In contrast, for FDR
the 3-factor model did not show improvement over HLA (P = .12) and performed
worse than the 10-factor model (P = .02) CONCLUSIONS: We have shown a 10-factor
risk model predicts development of diabetes in both GP and FDR children. While
this model was superior to a minimal model in FDR, it did not confer improvement
in GP. Differences in model performance in FDR vs GP children may lead to
important insights into screening strategies specific to these groups.
PMID- 28695613
TI - NGL-3-induced presynaptic differentiation of hippocampal neurons in an afadin
dependent, nectin-1-independent manner.
AB - A hippocampal mossy fiber synapse, which is implicated in learning and memory,
has a complex structure. We have previously shown using afadin-deficient mice
that afadin plays multiple roles in the structural and functional
differentiations of this synapse. We investigated here using a co-culture system
with cultured hippocampal neurons and non-neuronal COS-7 cells expressing
synaptogenic cell adhesion molecules (CAMs) whether afadin is involved in the
presynaptic differentiation of hippocampal synapses. Postsynaptic CAMs NGL-3
(alias, a Lrrc4b gene product) and neuroligin induced presynaptic differentiation
by trans-interacting with their respective presynaptic binding CAMs LAR (alias, a
Ptprf gene product) and neurexin. This activity of NGL-3, but not neuroligin, was
dependent on afadin, but not the afadin-binding presynaptic CAM nectin-1. The
afadin-binding postsynaptic CAM nectin-3 did not induce presynaptic
differentiation. Immunofluorescence and immunoelectron microscopy analyses showed
that afadin was localized mainly at puncta adherentia junctions, but partly at
synaptic junctions, of the mossy fiber synapse. beta-Catenin and gamma-catenin
known to bind to LAR were co-immunoprecipitated with afadin from the lysate of
mouse brain. These results suggest that afadin is involved in the NGL-3-LAR
system-induced presynaptic differentiation of hippocampal neurons cooperatively
with beta-catenin and gamma-catenin in a nectin-1-independent manner.
PMID- 28695614
TI - Use of anti-inflammatory analgesics in sickle-cell disease.
AB - WHAT IS KNOWN AND OBJECTIVE: Non-steroidal anti-inflammatory drugs (NSAIDs) have
been commonly used to treat pain in sickle-cell disease (SCD), but NSAID use is
associated with renal, gastrointestinal and cardiovascular toxicities. Our
objective was to evaluate the use of aspirin and non-aspirin NSAIDs in SCD.
COMMENT: Despite analgesic and anti-inflammatory benefits in SCD, non-aspirin
NSAIDs are associated with renal, cardiovascular and gastrointestinal toxicities
in this patient population. Aspirin may have less renal and cardiovascular
toxicities. The different side effect profile of NSAIDs is related to the COX
1/COX-2 selectivity at their therapeutic doses. Individual risk factors and
genetic biomarkers should be considered when selecting appropriate NSAIDs and
their dose. WHAT IS NEW AND CONCLUSION: NSAIDs have the potential to be an
important component of pain regimens in SCD, but the use of NSAIDs should be
individualized based on potential side effects and patient risk factors and the
lowest effective dose should be prescribed with proper monitoring in patients
with SCD.
PMID- 28695615
TI - Sociodemographic Determinants of Waitlist and Posttransplant Survival Among End
Stage Liver Disease Patients.
AB - While regional organ availability dominates discussions of distribution policy,
community-level disparities remain poorly understood. We studied micro-geographic
determinants of survival risk and their distribution across Donor Service Areas
(DSAs). Scientific Registry of Transplant Recipients records for all adults
waitlisted for liver transplantation 2002-2014 were reviewed. The primary
exposure variables were county-level sociodemographic risk, as measured by the
Community Health Score (CHS), a previously-validated composite index local health
conditions, and distance to listing transplant center. Among 114 347 patients,
the median CHS was 19.4 (range: 0-40). Compared the lowest risk counties (CHS 1
10), highest-risk counties (CHS 31-40) had more black (14.6% vs. 5.4%), publicly
insured (44.9% vs. 33.0), and remote candidates (34.0% vs. 15.1% living >100
miles away). Higher-CHS candidates had greater waitlist mortality in Cox
multivariable (HR 1.16 for CHS 31-40, 95% CI 1.11-1.21) and competing risks
analysis (sHR 1.07, 95% CI 0.99-1.14). Post-transplant survival was similar
across CHS quartiles. Living >25 miles from the transplant center conferred
excess mortality risk (sHR 1.08, 95% CI 1.03-1.12). Proposed distribution changes
would disproportionately impact DSAs with more high-CHS or distant candidates.
Low-income, rural and minority patients experience excess mortality while
awaiting transplant, and risk disproportionately worse outcomes with reduced
organ availability under current proposals.
PMID- 28695616
TI - Unprecedented Nucleophilic Additions of Highly Polar Organometallic Compounds to
Imines and Nitriles Using Water as a Non-Innocent Reaction Medium.
AB - In contrast to classic methods carried out under inert atmospheres with dry
volatile organic solvents and often low temperatures, the addition of highly
polar organometallic compounds to non-activated imines and nitriles proceeds
quickly, efficiently, and chemoselectively with a broad range of substrates at
room temperature and under air with water as the only reaction medium. Secondary
amines and tertiary carbinamines are furnished in yields of up to and over 99 %.
The significant solvent D/H isotope effect observed for the on-water nucleophilic
additions of organolithium compounds to imines suggests that the on-water
catalysis arises from proton transfer across the organic-water interface. The
strong intermolecular hydrogen bonds between water molecules may play a key role
in disfavoring protonolysis, which occurs extensively in other protic media such
as methanol. This work lays the foundation for reshaping many fundamental s-block
metal-mediated organic transformations in water.
PMID- 28695617
TI - Morbidity and mortality of elderly patients following cytoreductive surgery and
Hyperthermic Intraperitoneal Chemotherapy (HIPEC).
AB - AIM: Cytoreductive surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy
(HIPEC) is known to improve survival in selected patients with peritoneal
metastasis. However, there is limited data supporting the role of CRS and HIPEC
in elderly patients (>=65 years old). METHODS: A retrospective review of a
prospectively maintained database of patients who underwent CRS-HIPEC between
April 2001 and July 2015 from a single institution was performed. Patients were
divided into two groups non-elderly (<65 years old), and elderly (>=65 years
old). Clinico- pathological parameters, morbidity and overall (OS) and disease
free survival (DFS) of the patients were compared. RESULTS: A total of 177
patients (median age 52, range 9-74) underwent CRS-HIPEC with curative intent.
There were 159 non-elderly patients and 18 elderly patients. Median PCI scores
were 12 (0-39) for the non- elderly patients and 11 (1-29) for the elderly
patients (p=0.77). High-grade complications occurred in 39 non-elderly patients
(24.5%) and 8 elderly patients (44.4%) (p=0.79), while 58 non-elderly patients
(38.7%) and 7 elderly patients (41.2%) stayed in ICU for more than 1 day
(p=0.69). There was no difference in the 30-day mortality between the two groups
(0% vs. 0%, p=1). After a median follow-up of 16 months for all patients, there
was no difference in 5-years OS (51.0% vs. 59.6%, p=0.88) and 5-years DFS (23.3%
vs. 53.3%, p=0.60) between non-elderly and elderly patients. CONCLUSIONS:
Surgical outcomes after CRS-HIPEC do not differ significantly between non-elderly
and elderly patients. Hence, age should not be a contraindication in selecting
patients for CRS and HIPEC.
PMID- 28695618
TI - Quality predictors of parental satisfaction after birth of infants with life
limiting conditions.
AB - AIM: This study examines parental satisfaction with care received in the context
of a life-limiting foetal diagnosis and subsequent birth. METHODS: Survey methods
were utilised to embed the Quality Indicators (QI) and Parental Satisfaction of
Perinatal Palliative Care Instrument in a survey: 'The Voice of Parents'.
RESULTS: The web-based survey had a final sample of N = 405 parent responders.
Overall, parents reported satisfaction with care (80.2%; n = 393). Parents
satisfied with care reported higher agreement with quality indicator items for
all subscales. In total, 17 items from the 41-item instrument revealed the
ability to predict higher parental satisfaction when particular QI are reported.
CONCLUSION: This study has led to credible insights into parental satisfaction
with care given after the birth of an infant with a life-limiting condition. The
findings contribute to development of a model with a good fit in ascertaining the
importance of compassion, unhurried provider-patient communication and
bereavement interventions.
PMID- 28695619
TI - Muller glia and phagocytosis of cell debris in retinal tissue.
AB - Muller cells are the predominant glial cell type in the retina of vertebrates.
They play a wide variety of roles in both the developing and the mature retina
that have been widely reported in the literature. However, less attention has
been paid to their role in phagocytosis of cell debris under physiological,
pathological or experimental conditions. Muller glia have been shown to
phagocytose apoptotic cell bodies originated during development of the visual
system. They also engulf foreign molecules that are injected into the eye, cone
outer segments and injured photoreceptors. Phagocytosis of photoreceptor cell
debris in the light-damaged teleost retina is primarily carried out by Muller
cells. Once the microglial cells become activated and migrate to the
photoreceptor cell layer, the phagocytic activity of Muller cells progressively
decreases, suggesting a possible mechanism of communication between Muller cells
and neighbouring microglia and photoreceptors. Additionally, it has been shown
that phagocytic Muller cells acquire proliferating activity in the damaged
teleost retina, suggesting that engulfment of apoptotic photoreceptor debris
might stimulate the Muller glia to proliferate during the regenerative response.
These findings highlight Muller glia phagocytosis as an underlying mechanism
contributing to degeneration and regeneration under pathological conditions.
PMID- 28695620
TI - Correlated response in litter size components in rabbits selected for litter size
variability.
AB - A divergent selection experiment for the environmental variability of litter size
(Ve) over seven generations was carried out in rabbits at the University Miguel
Hernandez of Elche. The Ve was estimated as the phenotypic variance within the
female, after correcting for year-season and parity-lactation status. The aim of
this study was to analyse the correlated responses to selection in litter size
components. The ovulation rate (OR) and number of implanted embryos (IE) in
females were measured by laparoscopy at 12 day of the second gestation. At the
end of the second gestation, the total number of kits born was measured (TB).
Embryonic (ES), foetal (FS) and prenatal (PS) survival were computed as IE/OR,
TB/IE and TB/OR, respectively. A total of 405 laparoscopies were performed. Data
were analysed using Bayesian methodology. The correlated response to selection
for litter size environmental variability in terms of the litter size components
was estimated as either genetic trends, estimated by computing the average
estimated breeding values for each generation and each line, or the phenotypic
differences between lines. The OR was similar in both lines. However, after seven
generations of selection, the homogenous line showed more IE (1.09 embryos for
genetic means and 1.23 embryos for phenotypic means) and higher ES than the
heterogeneous one (0.07 for genetic means and 0.08 for phenotypic means). The
probability of the phenotypic differences between lines being higher than zero
(p) was 1.00 and .99, respectively. A higher uterine overcrowding of embryos in
the homogeneous line did not penalize FS; as a result, this line continued to
show a greater TB (1.01 kits for genetic means and 1.30 kits for phenotypic
means, p = .99, in the seventh generation). In conclusion, a decrease in litter
size variability showed a favourable effect on ES and led to a higher litter size
at birth.
PMID- 28695621
TI - Molecular Design of Thermally Activated Delayed-Fluorescent Emitters Using 2,2'
Bipyrimidine as the Acceptor in Donor-Acceptor Structures.
AB - Donor-acceptor-donor (D-A-D)-type thermally activated delayed fluorescence (TADF)
emitters 5,5'-bis{4-[9,9-dimethylacridin-10(9H)-yl]phenyl}-2,2'-bipyrimidine (Ac
bpm) and 5,5'-bis[4-(10H-phenoxazin-10-yl)phenyl]-2,2'-bipyrimidine (Px-bpm),
based on the 2,2'-bipyrimidine accepting unit, were developed and their TADF
devices were fabricated. The orthogonal geometry between the donor unit and the
2,2'-bipyrimidine accepting core facilitated a HOMO/LUMO spatial separation, thus
realizing thermally activated delayed fluorescence. The exhibited
electroluminescence ranged from green to yellow, depending on the donor unit,
with maximum external quantum efficiencies of up to 17.1 %.
PMID- 28695622
TI - Sleep disturbance by pramipexole is modified by Meis1 in mice.
AB - Meis homeobox 1 (Meis1) is a transcription factor functioning in the development
of the nervous system and the cardiovascular system. Both common and rare
variants within the gene have been associated with restless legs syndrome (RLS),
while its association with symptoms of insomnia has also been discovered
recently. RLS is associated with sleep disturbances, and while Meis1
haploinsufficiency is one of the most promising strategies for an RLS animal
model, sleep phenotyping of Meis1 knockout mice has never been conducted. We
report a detailed sleep analysis of heterozygous Meis1 knockout mice and
challenge it with pramipexole, a dopamine agonist used in the treatment of RLS.
At baseline, the Meis1-haploinsufficient mice had a trend towards lower delta
power in the electroencephalogram (EEG) during sleep compared to the wild-type
littermates, possibly indicating reduced sleep quality, but not sleep
fragmentation. Pramipexole had a sleep disrupting effect in both genotype groups.
In addition, it exerted differential effects on the EEG power spectra of the two
mouse lines, remarkably elevating the theta power of the mutant mice during
recovery more than that of the wild-types. In conclusion, Meis1
haploinsufficiency seems to have only a modest effect on sleep, but the gene may
interact with the sleep-disrupting effect of dopamine agonists.
PMID- 28695623
TI - Simultaneous valorization and biocatalytic upgrading of heavy vacuum gas oil by
the biosurfactant-producing Pseudomonas aeruginosa AK6U.
AB - Heavy vacuum gas oil (HVGO) is a complex and viscous hydrocarbon stream that is
produced as the bottom side product from the vacuum distillation units in
petroleum refineries. HVGO is conventionally treated with thermochemical process,
which is costly and environmentally polluting. Here, we investigate two petroleum
biotechnology applications, namely valorization and bioupgrading, as green
approaches for valorization and upgrading of HVGO. The Pseudomonas aeruginosa
AK6U strain grew on 20% v/v of HVGO as a sole carbon and sulfur source. It
produced rhamnolipid biosurfactants in a growth-associated mode with a maximum
crude biosurfactants yield of 10.1 g l-1 , which reduced the surface tension of
the cell-free culture supernatant to 30.6 mN m-1 within 1 week of incubation. The
rarely occurring dirhamnolipid Rha-Rha-C12 -C12 dominated the congeners' profile
of the biosurfactants produced from HVGO. Heavy vacuum gas oil was recovered from
the cultures and abiotic controls and the maltene fraction was extracted for
further analysis. Fractional distillation (SimDist) of the biotreated maltene
fraction showed a relative decrease in the high-boiling heavy fuel fraction (BP
426-565 degrees C) concomitant with increase in the lighter distillate diesel
fraction (BP 315-426 degrees C). Analysis of the maltene fraction revealed
compositional changes. The number-average (Mn) and weight-average (Mw) molecular
weights, as well as the absolute number of hydrocarbons and sulfur heterocycles
were higher in the biotreated maltene fraction of HVGO. These findings suggest
that HVGO can be potentially exploited as a carbon-rich substrate for production
of the high-value biosurfactants by P. aeruginosa AK6U and to concomitantly
improve/upgrade its chemical composition.
PMID- 28695624
TI - Life quality improvement in hoarse patients with early glottic cancer after
transoral laser microsurgery.
AB - BACKGROUND: The purpose of this study was to evaluate the recovery kinetics of
voice and quality of life (QOL) over time in patients with early glottic cancer
who underwent transoral laser microsurgery (TLM). METHODS: A prospective cohort
study was conducted in which acoustic and aerodynamic voice assessments and QOL
analyses were done using health-related questionnaires (European Organization for
Research and Treatment of Cancer Quality of Life Questionnaire-Core 30-questions
[EORTC-QLQ-C30] and European Organization for Research and Treatment of Cancer
Quality of Life Questionnaire-Head and Neck 35-questions [EORTC-QLQ-H&N35]) were
administered at designated times. RESULTS: Most voice laboratory parameters
worsened during the first month, then recovered to baseline after 6 months. The
QLQ-H&N35 speech subscale was significantly improved. Among the voice laboratory
parameters, pretreatment harmonics-to-noise ratio was an independent predictor (P
= .041) for improvement on the speech subscale at the endpoint. CONCLUSION:
Despite an initial deterioration of voice and QOL in the first month, patients
who underwent TLM recovered to a plateau since the sixth month and then to better
than preoperative status afterward. A greater improvement in QOL was seen in
patients with poorer baseline voice quality.
PMID- 28695625
TI - Water Oxidation by In Situ Generated [RuII (OH2 )(NCNHC O)(pic)2 ].
AB - A dinuclear ruthenium complex [RuII (NCNHC O)(pic)2 ]22+ (2) was firstly prepared
and characterized spectroscopically and electrochemically. Instead of the
conventional ligand exchange, complex 2 dissociates in situ to afford two single
site Ru aqua complexes, [RuII (OH2 )(NCNHC O)(pic)2 ]+ , which mediates water
oxidation through proton-coupled electron transfer events. In electrokinetic
studies, complex 2 demonstrated a TOF of 150.3 s-1 comparable to those state-of
the-art catalysts at neutral conditions. TONs of 2173 and 217 were attained in
chemical and photochemical water oxidation when 2 was used as a catalyst,
exhibiting good stability. Notably, a TOF of 1.3 s-1 was achieved at CAN-driven
water oxidation, which outperformed most of the reported single-site Ru
complexes, indicating that complex 2 is one of most active water oxidation
catalysts (WOCs) to date. The unique coordination configuration and outstanding
catalytic performance of complex 2 might shed light on the design of novel
molecular WOCs.
PMID- 28695626
TI - Mucosal glucagon-like peptide 1 (GLP-1) responses are mediated by calcitonin gene
related peptide (CGRP) in the mouse colon and both peptide responses are area
specific.
AB - BACKGROUND: Glucagon-like peptide (GLP)-1 is an incretin hormone and its mimetics
are proven antidiabetic and antiobesity drugs. GLP-1 exerts antimotility and
mucosal proliferative activities but its epithelial ion transport effects are
uncharacterized and these may contribute to the gastrointestinal (GI)
disturbance, i.e., diarrhea experienced with some GLP-1 mimetics. Our aim was to
establish GLP-1 agonist mechanisms and identify potential mucosal mediator(s) in
the colonic tissue from C57BL/6J mice. METHODS: A tissue survey of GLP-1
responses (using exendin 4, Ex4) and alpha-calcitonin gene-related peptide
(alphaCGRP) was undertaken, dividing the mouse colon into eight adjacent mucosal
submucosal preparations. Each preparation was voltage-clamped and changes in
short-circuit current (Isc) measured. The involvement of submucosal neurons in
GLP-1 agonism was tested using Ex(9-39) and tetrodotoxin (TTX), and CGRP
receptors were blocked with BIBN4094. KEY RESULTS: Ex4 responses along the length
of the colon were inhibited by the GLP-1 antagonist, Ex(9-39) or TTX, indicating
neural mediation in all colonic regions. In the ascending colon, Ex4 increased
Isc levels that were abolished by 10 nM BIBN4096, while in the descending colon
it reduced Isc levels that were again BIBN4096-sensitive, but at 1 MUM. The
latter alphaCGRP response was dependent on epithelial Cl- conductance and Na+ /K+
-ATPase, and was partially (~25%) peptide YY-mediated, but was not nitrergic,
somatostatin sst2 , or alpha2 -adrenoceptor-mediated. CONCLUSIONS AND INFERENCES:
GLP-1 modulates epithelial ion transport indirectly by activating CGRP-containing
submucosal enteric neurons in the mouse colon. This GLP-1-CGRP response was area
specific and could potentially contribute to the diarrheal side effect of certain
GLP-1R therapeutics.
PMID- 28695627
TI - Verrucous candidiasis of the orolabial mucosa: a clinicopathologic series.
PMID- 28695628
TI - The views of carers about support for their family member with an intellectual
disability: With a focus on positive behavioural approaches.
AB - This qualitative study explored the views of family carers about the support that
their adult children with an intellectual disability had received in relation to
their behaviour that challenged. There was a particular focus on positive
behavioural support (PBS), although some participants spoke more generally in
terms of positive approaches. Semi-structured interviews with eight family carers
were analysed using inductive thematic analysis. Four key themes were identified.
Good support, of which PBS was an example, was seen as both having reduced
behaviours that challenged and having a wider positive impact on the quality of
life of the individual and their families. Key features highlighted were:
technical knowledge and skill; a strong value base of warmth, acceptance and
respect; a collaborative, consistent approach; open communication; and the
extension of support to the family carer when needed. It was recognised that
there is a need for broad systemic change and for the application of a workforce
development model that takes account of the needs of staff, carers and those
working in wider systems that have contact with people with an intellectual
disability.
PMID- 28695629
TI - Caspase-11 non-canonical inflammasome: a critical sensor of intracellular
lipopolysaccharide in macrophage-mediated inflammatory responses.
AB - Inflammatory responses mediated by macrophages are part of the innate immune
system, whose role is to protect against invading pathogens. Lipopolysaccharide
(LPS) found in the outer membrane of Gram-negative bacteria stimulates an
inflammatory response by macrophages. During the inflammatory response,
extracellular LPS is recognized by Toll-like receptor 4, one of the pattern
recognition receptors that activates inflammatory signalling pathways and leads
to the production of inflammatory mediators. The innate immune response is also
triggered by intracellular inflammasomes, and inflammasome activation induces
pyroptosis and the secretion of pro-inflammatory cytokines such as interleukin
1beta (IL-1beta) and IL-18 by macrophages. Cysteine-aspartic protease (caspase)
11 and the human orthologues caspase-4/caspase-5 were recently identified as
components of the 'non-canonical inflammasome' that senses intracellular LPS
derived from Gram-negative bacteria during macrophage-mediated inflammatory
responses. Direct recognition of intracellular LPS facilitates the rapid
oligomerization of caspase-11/4/5, which results in pyroptosis and the secretion
of IL-1beta and IL-18. LPS is released into the cytoplasm from Gram-negative
bacterium-containing vacuoles by small interferon-inducible guanylate-binding
proteins encoded on chromosome 3 (GBPchr3 )-mediated lysis of the vacuoles. In
vivo studies have clearly shown that caspase-11-/- mice are more resistant to
endotoxic septic shock by excessive LPS challenge. Given the evidence, activation
of caspase-11 non-canonical inflammasomes by intracellular LPS is distinct from
canonical inflammasome activation and provides a new paradigm in macrophage
mediated inflammatory responses.
PMID- 28695630
TI - A pilot phase II study of ofatumumab monotherapy for extranodal marginal zone B
cell lymphoma of the mucosa-associated lymphoid tissue (MALT) lymphoma.
AB - These are the final results of the Ofatumumab in MALT lymphoma study (O-MA 1), a
pilot phase II trial evaluating the capacity and safety of ofatumumab to induce
objective responses in patients with Helicobacter pylori eradication refractory
or extragastric MALT lymphoma. Ofatumumab was given at 4 weekly doses (1000 mg)
followed by 4 doses at 2-month intervals starting at week 8. According to
protocol, a total of 16 patients were recruited (median age 69 years; range 38
85). Thirty one percent (5/16) of patients had primary gastric MALT lymphoma
while the remaining 69% (11/16) presented with extragastric manifestations.
Seventy-five percent (12/16) had localized lymphoma and 4 patients disseminated
disease. The overall response rate to treatment with ofatumumab was 81% (13/16),
with the median time to best response being 5.5 months. In detail, 50% (8/16)
achieved complete remission; 31% (5/16), partial remission; and 19% (3/16),
disease stabilization as best response. However, 1 patient with gastric lymphoma
and complete remission at second restaging had a relapse at final assessment but
ongoing complete remission during further follow-up. Tolerability was excellent
accept low-grade infusion reactions occurring in 86% (14/16). At a median follow
up time of 25 months only 1 patient has relapsed suggesting durable responses in
the majority of patients. This pilot trial shows clearly that ofatumumab is
active and safe for the treatment of MALT lymphoma.
PMID- 28695631
TI - Extending decomposition analysis to account for unobserved heterogeneity and
persistence in health behavior: Income-related smoking inequality among Swedish
women.
AB - This article suggests an enrichment of the standard method for decomposition of
the concentration index to account for unobserved heterogeneity and persistence
in health behavior. As the underlying regression model in the decomposition, this
approach uses a dynamic random-effect probit that both consider individual
heterogeneity, using a Mundlak type of specification, and applies a simple
solution to account for smoking persistence. I illustrate the suggested approach
using a panel of Swedish women in Statistics Sweden's Survey of Living Conditions
for one vital health-related behavior, smoking. The results highlight the
importance of persistence and show that education and living in a single
household are the main drivers of income-related smoking inequality.
PMID- 28695632
TI - The effect of mirtazapine on gastric accommodation, gastric sensitivity to
distention, and nutrient tolerance in healthy subjects.
AB - BACKGROUND: Disturbances of gastric motor function of functional dyspepsia (FD)
have been implicated in the pathogenesis of the symptoms, and hence, motility
modifying agents are considered for its treatment. Mirtazapine was recently shown
to improve symptoms and increase nutrient tolerance in FD patients with weight
loss. We aim to evaluate the effect of mirtazapine on gastric sensorimotor
function in healthy volunteers (HV). METHODS: Thirty-one HV underwent an
intragastric pressure (IGP) and barostat measurements on separate days before and
after 3 weeks of placebo or mirtazapine (15 mg). Gastric compliance, sensitivity
and accommodation (GA) measured by the barostat. GA was quantitated as the
difference (delta) in intra-balloon volume before and after ingestion of 200 mL
of a nutrient drink (ND). GA measured by IGP was quantitated as the drop of IGP
from baseline during the intragastric infusion of ND until maximal satiation. KEY
RESULTS: Mirtazapine significantly increased the bodyweight of subjects (67.8+/
3.7 to 69.1+/-3.7 kg; P=.01). Barostat results showed no effect on gastric
compliance, sensitivity, and GA. Nutrient tolerance was not affected after
treatment (1170+/-129.4 vs 1104+/-133.6 kcal; P=.4), and mirtazapine was
associated with lower symptom ratings. The IGP drop during meal ingestion was
significantly suppressed (area under the curve: -43.3+/-4.5 mm Hg vs -28.9+/-3.1
mm Hg; P=.005). CONCLUSIONS & INFERENCES: In HVs, the occurrence of weight gain
and decreased meal-induced symptoms in spite of a suppressed meal-induced IGP
drop, point towards a central mode of action. Mirtazapine does not display
changes in gastric sensorimotor function that could explain its beneficial
effects on symptoms and nutrient tolerance in FD.
PMID- 28695633
TI - Industry Responsibilities in Tackling Direct-to-Consumer Marketing of Unproven
Stem Cell Treatments.
AB - The direct-to-consumer marketing of unproven stem cell interventions (SCIs) is a
serious public health concern. Regulations and education have had modest impact,
indicating that different actors must play a role to stop this unfettered market.
We consider the role of the biotech industry in tackling unproven SCIs. Grounded
in the concept of corporate social responsibility, we argue that biotech
companies should screen consumers to ensure that products and services are being
used appropriately and educate employees about unproven SCIs.
PMID- 28695634
TI - Patient-reported outcomes in multiple sclerosis: a systematic comparison of
available measures.
AB - Multiple patient-reported outcomes (PROs) are currently being used in multiple
sclerosis (MS) but their application is inconsistent and guidance on the
appropriateness of each tool is lacking. The objective of our study was to
identify MS-specific PROs and systematically to assess the development process
and the reliability and validity of various instruments. A systematic literature
search was conducted on multiple data sources, including MEDLINE, Embase (using
the Ovid platform) and Google Scholar, from 1996 to March 2015. Search terms
included combinations of MS, PROs and quality of life. Randomized controlled
trials or observational studies conducted on patients with MS and published in
English were included. In addition, the PROQOLID database was explored. The MS
specific PROs were systematically assessed using the Evaluating the Measurement
of Patient-Reported Outcomes tool. In total, 8094 articles were screened and 405
PROs were identified from 1102 relevant articles. PROs were classified into MS
specific (n = 82) and non-MS-specific (n = 323). The results for the eight PROs
that are most commonly used in MS clinical trials are presented here. For these
eight PROs, the overall summary scores ranged between 50.1 and 68.7. The Multiple
Sclerosis Impact Scale-29 had the best overall mean score (68.7), followed by the
Leeds Multiple Sclerosis Quality of Life (67.0). This is the first study to
provide a standardized assessment of all PROs for MS. There is a lack of data on
content validity for PROs used in MS research, which indicates the need for a
robust instrument in MS developed according to the US Food and Drug
Administration guidelines.
PMID- 28695635
TI - Taurine does not improve the quality of short-term stored rabbit spermatozoa in
vitro.
AB - This study examines the impact of taurine on the viability, morphology and
acrosome integrity of rabbit spermatozoa in vitro. Semen samples, obtained from
four to five sexually mature and healthy New Zealand White rabbits, were pooled
in heterospermic semen sample. This was divided and treated with taurine in a
concentration of 0 (control), 1.5, 7, 12.5, 50 mM to a final concentration of 108
spermatozoa/ml. The samples were then incubated at 37 degrees C for 4 hr. A
combination of fluorescent probes SYBR-14/propidium iodide/PNA-Alexa Fluor 647
was used to assess spermatozoa viability and acrosome integrity on a flow
cytometer. The sperm morphology was evaluated under a light microscope following
fixation in 1.5% paraformaldehyde. The experiment was repeated three times.
According to the obtained results, the spermatozoa neither could have benefit
from immediate taurine treatment, nor had they after 4-hr incubation with respect
to viability and acrosome integrity. Taurine did not initially alter the total
and acrosome morphology of treated spermatozoa nor has it by 4 hr upon treatment.
In conclusion, taurine may have no protective effect on the viability, morphology
and acrosome integrity of short-term stored rabbit spermatozoa.
PMID- 28695636
TI - Triphenylamine-Functionalized Silsesquioxane-Based Hybrid Porous Polymers:
Tunable Porosity and Luminescence for Multianalyte Detection.
AB - A series of hybrid luminescent porous polymers (HLPPs) are synthesized through
Friedel-Crafts reactions by tuning the molar ratio of triphenylamine (TPA) to
octavinylsilsesquioxane (OVS). The synthesized HLPPs exhibit high Brunauer-Emmett
Teller surface areas up to 841+/-10 m2 g-1 , high thermal stability with
decomposition temperatures (Td at 5 wt %) up to 440 degrees C in air, and strong
blue-violet luminescence at approximately 450 nm. The porosities and luminescent
properties of the HLPPs, including emission wavelength, intensity, fluorescence
quantum yield, and monochromaticity, can be tuned easily by modulating the molar
ratio of TPA to OVS. In addition, the polymers may serve as excellent fluorescent
probes for multianalyte detection, with high fluorescence quenching coefficients
(KSV ) of 8900 and 4400 m-1 for Fe3+ and Cu2+ , respectively.
PMID- 28695637
TI - Prenatal management of fetal intrapericardial teratoma: a systematic review.
AB - OBJECTIVES: The purpose of this systematic review is to provide a comprehensive
overview on the clinical course, perinatal outcome, and effectiveness of prenatal
management options for pericardial teratoma. METHODS: A comprehensive search
including Ovid MEDLINE, Ovid EMBASE, and Scopus was conducted from inception to
September 2016. All studies that reported the prenatal course of pericardial
teratoma in singleton or twin gestations were considered eligible. Standardized
forms were used for data abstraction by two independent reviewers. RESULTS: Out
of 217 screened abstracts, 59 studies reporting 67 fetuses with pericardial
teratoma were included. Twenty-three singleton fetuses and 3 fetuses in twin
gestations underwent prenatal treatment, and 20 (76.9%) of them were hydropic at
the time of intervention. Of those, 15/20 (75%) had a favorable outcome. In the
non-intervention group (n = 41), 26 (63.4%) developed hydrops, and out of those,
8 (30.8%) had a favorable outcome. CONCLUSION: Prenatal fluid drainage and other
prenatal techniques have been utilized in the treatment of intrapericardial
teratoma. While most fetuses tolerated pericardiocentesis, the neonatal benefit
of this procedure is still uncertain, and outcomes of other interventions had
variable success. Prenatal intervention for pericardial teratoma may be an option
in specialized units but, given the maternal and fetal risks, needs careful
consideration. (c) 2017 John Wiley & Sons, Ltd.
PMID- 28695638
TI - Highly Fluorescent Pyridinium Betaines for Light Harvesting.
AB - We report the findings of our experimental and theoretical investigations into
the properties of pyridinium enolates and their potential utility in light
harvesting applications, such as in luminescent solar concentrators (LSCs). We
present the synthesis, structures, photophysical characterization, and
wavefunction-based quantum-chemical studies of five cyclobetaines. The
performance of an LSC device incorporating one of these cyclobetaines is shown to
be comparable to state-of-the-art devices.
PMID- 28695639
TI - Variation in aluminium patch test reactivity over time.
AB - BACKGROUND: Contact allergy to aluminium has been reported more frequently in
recent years. It has been pointed out that positive patch test reactions to
aluminium may not be reproducible on retesting. OBJECTIVES: To investigate
possible variations in patch test reactivity to aluminium over time. METHODS:
Twenty-one adults, who had previously reacted positively to aluminium, were patch
tested with equimolar dilution series in pet. of aluminium chloride hexahydrate
and aluminium lactate, four times over a period of 8 months. RESULTS: Thirty-six
of 84 (43%) serial dilution tests with aluminium chloride hexahydrate and 49 of
84 (58%) serial dilution tests with aluminium lactate gave negative results. The
range of reactivity varied between a negative reaction to aluminium chloride
hexahydrate at 10% and/or to aluminium lactate at 12%, and a positive reaction to
aluminium chloride hexahydrate at 0.1% and/or to aluminium lactate at 0.12%. The
highest individual difference in test reactivity noticed was 320-fold when the
two most divergent minimal eliciting concentrations were compared. CONCLUSIONS:
The patch test reactivity to aluminium varies over time. Aluminium-allergic
individuals may have false-negative reactions. Therefore, retesting with
aluminium should be considered when there is a strong suspicion of aluminium
contact allergy.
PMID- 28695640
TI - Seed dispersal by hornets: An unusual insect-plant mutualism.
AB - Vespicochory, seed dispersal by hornets, is a rare seed dispersal mechanism in
angiosperms and, to date, there are few records of this phenomenon. Through field
investigations and behavioral assays conducted in four populations of Stemona
tuberosa from 2011-2016, we demonstrate that hornets are the primary seed
dispersers of S. tuberosa and play an important role in "long-distance" seed
dispersal in this species. Furthermore, some ant species act as secondary
dispersers and may transport the seeds to safe sites. Hornets and ants provide
complementary seed dispersal at different spatial scales. This unique example of
insect-plant mutualism may be an underestimated but important strategy to ensure
"long-distance" seed dispersal in other myrmecochorous plants.
PMID- 28695641
TI - Favorable factors for preserving bladder function after nerve-sparing radical
hysterectomy: A protocol-based validation study.
AB - OBJECTIVES: To investigate favorable factors of nerve-sparing radical
hysterectomy (NSRH) for preserving the pelvic autonomic nerves and subsequent
bladder function and to compare the safety between NSRH and conventional radical
hysterectomy (CRH) for cervical cancer. METHODS: We recruited 87 consecutive
patients with IB1-IIA cervical cancer who underwent NSRH, and reviewed the
information of 81 patients who received CRH for historical comparisons. One
gynaecologic oncologist performed all operations. RESULTS: IB1 disease was the
only favorable factor for unilateral or bilateral preservation (adjusted OR,
0.245; 95% CI, 0.077-0.774), whereas IB1 disease and squamous cell carcinoma
(SqCC) were favorable for bilateral preservation (adjusted ORs, 0.336 and 0.116;
95% CIs, 0.162-0.982 and 0.023-0.581). The median duration of postoperative
catheterization (DPC) was different among bilateral, unilateral and failed
preservation (median 6 vs 18 vs 90 days; P < 0.001). The median DPC was shorter
in NSRH patients with stage IB1 disease or SqCC (7 vs 14 days; P < 0.05) despite
no difference between NSRH and CRH in those with IB2-IIA disease or non-SqCC.
Survival was not different between NSRH and CRH patients. CONCLUSIONS: IB1
disease and SqCC are favorable for preserving the pelvic autonomic nerves and
subsequent bladder function without compromising survival outcomes in patients
treated with NSRH.
PMID- 28695642
TI - Maternal intrapartum antibiotic treatment continues to exert a bactericidal
effect on the umbilical cord and peripheral venous blood of newborn infants.
AB - AIM: It is unclear whether maternal intrapartum antibiotic treatment (IAT)
continues to exert a bactericidal effect on common pathogens in neonates. We
studied the in vitro bactericidal effect of IAT on the cord and peripheral venous
blood of newborn infants. METHODS: Umbilical cord and peripheral venous blood
from newborn infants born at Kaplan Medical Center, Israel, from April to October
2014 were studied for serum bactericidal titres against Group B Streptococcus
(GBS) and Escherichia coli (E. coli) strains. We studied 60 samples of umbilical
cord blood and 18 samples of peripheral venous blood from 60 newborn infants
whose mothers received IAT. The controls were 10 samples of cord blood from
mothers without IAT. RESULTS: Cord blood exerted a bactericidal effect against
98% of GBS isolates but only 8% of E.coli isolates. Peripheral blood exerted a
bactericidal effect against GBS in 94% of cases, but not against E. coli. No
bactericidal effect was seen in the blood from the controls. CONCLUSION: We found
a continued bactericidal effect of umbilical cord blood and neonatal peripheral
blood from newborn infants of IAT-treated mothers, mainly against GBS, but rarely
against E. Coli. These findings may assist clinicians treating at-risk infants
exposed to IAT.
PMID- 28695643
TI - Re: Gungor F, Kilic T, Akyol KC, et al. Diagnostic value and effect of bedside
ultrasound in acute appendicitis in the emergency department.
PMID- 28695645
TI - Health and Brexit.
PMID- 28695646
TI - The accuracy of the HemoCue WBC DIFF in assessing blood eosinophils depends on
the clinical setting and medical condition.
PMID- 28695647
TI - Experiences of participating in return-to-work group programmes for people with
musculoskeletal disorders: A focus group study.
AB - PURPOSE: The present study aimed to explore the experiences of individuals with
musculoskeletal disorders (MSDs) who had participated in return-to-work group
programmes (RTW-GPs) and to assess whether the programmes had had an impact on
their work disability. METHOD: Three focus group interviews and one individual
interview were conducted involving 17 women (mean age = 47) with MSDs who had
completed RTW-GPs. All interviews were audio-recorded, transcribed verbatim and
analysed using thematic analyses. RESULTS: Participant experiences were
categorised into three main themes: changed way of thinking, the importance of
being able to work, and a changed lifestyle. The respondents said that
participation in the RTW-GPs had enabled them to shift their focus from problems
to opportunities. They had become more aware of strategies to enhance their
energy levels and continue working. Several participants had reduced their work
hours to achieve a better balance between work and daily life. Many participants
had also changed their lifestyle habits, which had led to weight reduction, more
energy and less pain. CONCLUSION: The study participants had attained a
heightened awareness of what they could do to continue working. Many participants
had introduced changes in their daily lives, with consequences for employment,
social life and lifestyle. The findings suggest that RTW-GPs can help people with
MSDs to remain in employment and prevent absenteeism.
PMID- 28695648
TI - Three glycosylated serine-rich repeat proteins play a pivotal role in adhesion
and colonization of the pioneer commensal bacterium, Streptococcus salivarius.
AB - Bacterial adhesion is a critical step for colonization of the host. The pioneer
colonizer and commensal bacterium of the human gastrointestinal tract,
Streptococcus salivarius, has strong adhesive properties but the molecular
determinants of this adhesion remain uncharacterized. Serine-rich repeat (SRR)
glycoproteins are a family of adhesins that fulfil an important role in adhesion.
In general, Gram-positive bacterial genomes have a unique SRR glycoprotein
encoding gene. We demonstrate that S. salivarius expresses three large and
glycosylated surface-exposed proteins - SrpA, SrpB and SrpC - that show
characteristics of SRR glycoproteins and are secreted through the accessory
SecA2/Y2 system. Two glycosyltransferases - GtfE/F - encoded outside of the
secA2/Y2 locus, unusually, perform the first step of the sequential glycosylation
process, which is crucial for SRR activity. We show that SrpB and SrpC play
complementary adhesive roles involved in several steps of the colonization
process: auto-aggregation, biofilm formation and adhesion to a variety of host
epithelial cells and components. We also show that at least one of the S.
salivarius SRR glycoproteins is important for colonization in mice. SrpA, SrpB
and SrpC are the main factors underlying the multifaceted adhesion of S.
salivarius and, therefore, play a major role in host colonization.
PMID- 28695649
TI - Single-center experience of antifungal prophylaxis for coccidioidomycosis in
heart transplant recipients within an endemic area.
AB - In endemic regions, coccidioidomycosis causes substantial morbidity and mortality
for patients receiving solid organ transplants. We aimed to demonstrate the
effect of antifungal coccidioidal prophylaxis in heart transplant (HT)
recipients. We retrospectively reviewed the electronic health records of all
patients who received HTs between October 19, 2005, and December 13, 2014. We
collected information regarding antifungal regimens and determined whether
patients subsequently developed infections. Our 174-person cohort all received
antifungal prophylaxis for at least 6 months (mean follow-up, 53.8 months). One
proven and one probable coccidioidal infection (each, 0.6%) occurred during the
study period. The incidence of coccidioidomycosis was 0.6% at 1 year and 2.3% at
5 years. No cases of proven coccidioidomycosis occurred within 2 years after
transplantation. No patients developed disseminated disease, and no sentinel
events were attributed to coccidioidomycosis. Both fluconazole and voriconazole
were well tolerated. In the absence of intolerance or contraindication, we
suggest continuing a universal antifungal prophylactic regimen with fluconazole
for at least 6-12 months in HT recipients residing in a coccidioidomycosis
endemic area.
PMID- 28695650
TI - A Novel Tropoloisoquinoline Alkaloid, Neotatarine, from Acorus calamus L.
AB - A novel tropoloisoquinoline alkaloid, neotatarine (1), was isolated from the 95%
ethanol extract of the rhizome parts of Acorus calamus L. The chemical structure
was unambiguously elucidated by spectroscopic and single-crystal X-ray
diffraction analysis. Neotatarine (1) exhibited significantly inhibitory activity
against Abeta25 - 35 induced PC12 cell death with 2, 4 and 8 MUm comparing with
the assay control (P < 0.01).
PMID- 28695651
TI - The nurse's role in palliative care: A qualitative meta-synthesis.
AB - AIMS AND OBJECTIVES: To explore how nurses, across various health systems,
describe their role in providing palliative care for patients with life
threatening illnesses. BACKGROUND: Despite the fact that nurses make up the
largest group of healthcare professionals, little is known about their role in
palliative care, across health services. DESIGN: A qualitative systematic review
of studies. METHODS: A search was made for relevant articles, published between
January 2000-June 2016. Twenty-eight articles were selected and analysed using
thematic synthesis. RESULTS: The themes that emerged from the analysis were as
follows: Being available, which gave nurses a pivotal role in palliative care and
paved the way for Being a coordinator of care for patients and relatives, as well
as for other health personnel. Doing what's needed was to handle an enormous
breadth of activities, always in a holistic framework of understanding. Being
attentively present and dedicated as well as using flexible and nontraditional
methods was essential in the role. Standing in demanding situations dealt with
lack of time and resources, limited legitimacy, handling ethical dilemmas and
being in need of support and knowledge. CONCLUSION: Being available as well as a
coordinator characterises the nurse's role across healthcare systems. The nurse
acts as a link between different levels of health care, between different
professions and between patient and family, which contribute to ensuring the
quality of care to the individual patient. The review illuminates that the basic
tenets of care in nursing are also fundamental to the nurse's role in palliative
care. To be able to give individually tailored palliative care to patients with
life-threatening illnesses and their relatives, the nurses need all their
knowledge of basic nursing. Situations challenge nurses in practical, relational
and moral dimensions of care and make demands on their role in a comprehensive
way. RELEVANCE TO CLINICAL PRACTICE: Nurses need knowledge and training, guidance
and support to fulfil their role.
PMID- 28695652
TI - Production of functionalized oligo-isoprenoids by enzymatic cleavage of rubber.
AB - In this study, we show the proof of concept for the production of defined oligo
isoprenoids with terminal functional groups that can be used as starting
materials for various purposes including the synthesis of isoprenoid-based
plastics. To this end, we used three types of rubber oxygenases for the enzymatic
cleavage of rubber [poly(cis-1,4-isoprene)]. Two enzymes, rubber oxygenase
RoxAXsp and rubber oxygenase RoxBXsp , originate from Xanthomonas sp. 35Y; the
third rubber oxygenase, latex-clearing protein (LcpK30 ), is derived from Gram
positive rubber degraders such as Streptomyces sp. K30. Emulsions of polyisoprene
(latex) were treated with RoxAXsp , RoxBXsp , LcpK30 or with combinations of the
three proteins. The cleavage products were purified by solvent extraction and
FPLC separation. All products had the same general structure with terminal
functions (CHO-CH2 - and -CH2 -COCH3 ) but differed in the number of intact
isoprene units in between. The composition and m/z values of oligo-isoprenoid
products were determined by HPLC-MS analysis. Our results provide a method for
the preparation of reactive oligo-isoprenoids that can likely be used to convert
polyisoprene latex or rubber waste materials into value-added molecules,
biofuels, polyurethanes or other polymers.
PMID- 28695653
TI - Bacterial cellulose as an example product for sustainable production and
consumption.
AB - Life cycle of bacterial cellulose. Sustainable production and consumption of bio
based products are showcased using bacterial cellulose as an example.
PMID- 28695654
TI - Synthesis of Amidines from Amides Using a Nickel-Catalyzed Decarbonylative
Amination through CO Extrusion Intramolecular Recombination Fragment Coupling.
AB - A catalytic synthesis of amidines from amides has been established for the first
time. The newly developed CO extrusion recombination process takes advantage of
an inexpensive nickel(II) catalyst and provides the corresponding amidines with
high efficiency. The intramolecular fragment coupling shows excellent
chemoselectivity, starts from readily available amides, and provides a valuable
alternative amidine synthesis protocol.
PMID- 28695655
TI - Sex differences in the decoding of pain-related body postures.
AB - BACKGROUND: Pain can be detected through nonverbal cues, including facial
expressions, vocalisations, and body posture. While there are sex differences in
how emotional expressions are recognized, these differences have not always been
found for pain. One reason for this inconsistency may be methodological, as pain
studies tend not to be designed to investigate individual differences in
expression recognition. Also, few studies consider sex differences outside facial
expression. METHODS: This study applied an image degradation method used to
examine individual differences in emotion recognition, to investigate sex
differences in the decoding of pain body postures. Forty participants (20 male)
were presented with a series of body posture images depicting pain at differing
levels of image degradation. Happiness, anger and sadness expressions were also
included for comparison. RESULTS: Results showed significant effects of image
degradation, affect type, and actor sex. Females were rated as presenting more
intense pain than males; this pattern was also found for fear, but not anger or
happiness. The accuracy of pain intensity judgements was reduced as image clarity
decreased. Male actors depicting pain were recognized with greater accuracy than
female actors. Interestingly, similar patterns were found for anger and fear
expressions. CONCLUSIONS: We conclude that sex has a significant influence on
pain decoding under certain conditions, and while there are similarities with the
way pain and core emotions are decoded, this may depend on the type of emotion
presented. This also suggests that sex-related effects in the recognition of pain
expressions may include body postural cues. SIGNIFICANCE: Observer's judgements
of pain displayed through body postures are driven by the sex of the person in
pain.
PMID- 28695656
TI - Anatolian honey is not only sweet but can also protect from breast cancer: Elixir
for women from artemis to present.
AB - Natural products with bioactive components are widely studied on various cancer
cell lines for their possible cytotoxic effects, recently. Among these products,
honey stands out as a valuable bee product containing many active phenolic
compounds and flavonoids. Numerous types of multifloral honey and honeydew honey
are produced in Turkey owing to its abundant vegetation. Therefore, in this
study, we investigated the cytotoxic effects of particular tree-originated honeys
from chestnut, cedar, pine, and multifloral honey on cell lines representing
different types of the most common cancer of women, breast cancer, MCF7, SKBR3,
and MDAMB-231, and fibrocystic breast epithelial cell line, MCF10A as a control.
All honey samples were analyzed biochemically. The dose- (1, 2.5, 5, 7.5, and 10
ug/mL) and time (24th, 48th, and 72nd hours)-dependent effects of ethanol/water
solutions of the honey samples were scrutinized. Cell viability/cytotoxicity was
evaluated by the water soluble tetrazolium Salt-1 (WST-1) method. Apoptotic
status was detected by Annexin V-PI assay using FACSCalibur. The statistical
analysis was performed using GraphPad Prism 6 and the clustering data analysis
with the R programming language. The biochemical analyses of the honey samples
showed that the tree-originated honey samples contained more total phenolic
compounds than the multifloral honey. Phenolic content of the honey types
increases in order of multifloral, pine, cedar, and chestnut, respectively, which
is compatible with their cytotoxic affectivity and dark color. In addition, the
antioxidant capacity of the studied honey types was observed to increase in order
of multifloral < pine < cedar ? chestnut. According to the WST-1 data, chestnut
honey induced cytotoxicity over 50% on all the cell lines, including the control
MCF10A cells, even with low doses (honey concentrations starting from 1 ug/mL) (P
< 0.0001). Similarly, Cedar honey was observed to be the second most effective
honey in this study. Cedar honey, with the dose of 1 ug/mL, was detected
statistically highly significant on MCF10A, MCF7, and SKBR3. In contrast, pine
honey showed dramatically significant cytotoxicity only on the MDAMB 231 cells
with a 1 ug/mL dose at the same time point (P = 0.018). While pine honey caused
an anticancer effect on the MCF-7 and SKBR3 cancer cell lines with a 2.5-5 ug/mL
dose (P < 0.0001), like cedar and chestnut honeys, it increased the viability of
the MCF10A control cells with the doses of 2.5-5 ug/mL. It only showed
cytotoxicity with higher doses (10 ug/mL) on the MCF10A cell line (P < 0.0001).
Moreover, we have observed that the multifloral and artificial honey samples were
mostly ineffective or increased cell viability with the doses of 1-5 ug/mL.
Apoptotic effects of the other honey samples on the MCF-7 cell line were found as
chestnut> pine> cedar> multifloral in the Annexin V-propidium iodide (PI)
analysis. Chestnut, cedar, and pine honey displayed a remarkably cytotoxic effect
on breast cancer cell lines, MCF7, SKBR3, and even on the most aggressive MDAMB
231, representing the triple negative breast cancer, which lacks of targeted
anticancer therapy. The chestnut and cedar honeys stand out to be the most
cytotoxic on all cell lines, while pine honey was found to be the least toxic on
control cells with appropriate toxicity on the cancer cells. (c) 2017 IUBMB Life,
69(9):677-688, 2017.
PMID- 28695658
TI - Fecal Microbial Transplantation in Inflammatory Bowel Disease: A Movement Too Big
to Be Ignored.
AB - The development of new therapies for inflammatory bowel disease is plagued by
high costs, potential side effects, and variable levels of effectiveness. Fecal
microbial transplant in inflammatory bowel diseases can offer an alternative to
traditionally developed pharmacologic therapies and has demonstrated the ability
to induce disease remission in randomized control trials. However, questions
remain about the ultimate role of this therapy in disease management, including
long term safety, and the optimal composition of transplanted stool.
PMID- 28695657
TI - HLA haplotypes in primary sclerosing cholangitis patients of admixed and non
European ancestry.
AB - Primary sclerosing cholangitis (PSC) is strongly associated with several human
leukocyte antigen (HLA) haplotypes. Due to extensive linkage disequilibrium and
multiple polymorphic candidate genes in the HLA complex, identifying the alleles
responsible for these associations has proven difficult. We aimed to evaluate
whether studying populations of admixed or non-European descent could help in
defining the causative HLA alleles. When assessing haplotypes carrying HLA
DRB1*13:01 (hypothesized to specifically increase the susceptibility to chronic
cholangitis), we observed that every haplotype in the Scandinavian PSC population
carried HLA-DQB1*06:03. In contrast, only 65% of HLA-DRB1*13:01 haplotypes in an
admixed/non-European PSC population carried this allele, suggesting that further
assessments of the PSC-associated haplotype HLA-DRB1*13:01-DQA1*01:03-DQB1*06:03
in admixed or multi-ethnic populations could aid in identifying the causative
allele.
PMID- 28695659
TI - Epstein-Barr virus-negative extranodal "true" natural killer-cell lymphoma
harbouring a KDM6A mutation.
AB - Extranodal natural killer (NK)/T-cell lymphoma, nasal type (ENKTL) is an
extranodal aggressive T or NK-cell lymphoma that is characteristically associated
with Epstein-Barr virus (EBV) infection and cytotoxic tissue-destructive
features. Although ENKTL is described as a distinct entity according to the 2008
WHO classification, a considerable complexity is associated with the differential
diagnosis of other T-cell lymphomas with respect to tumour cell origins,
locations, and the presence of EBV infection, as well as molecular and
cytogenetic abnormalities. Here, we report a rare case of EBV-negative ENKTL,
where the absence of EBV in the true NK-lineage cells was confirmed by extensive
phenotypic and genotypic analyses. Furthermore, using the next-generation
sequencing approach, we identified mutations in the tumour suppressor genes KDM6A
and TP53. The clinicopathological characteristics were almost similar to those of
EBV-positive ENKTL, except for the absence of EBV and histologically apparent
angioinvasiveness. This is the first reported ENKTL case with mutations in the
KDM6A gene. KDM6A is one of the histone-modifying genes that are mutated in many
human diseases including haematological cancers. Epigenetic regulation of gene
expression has recently been demonstrated in ENKTL, and a similar pathway is
thought to play an oncogenic role in EBV-negative ENKTL. Our report shows the
extent of comprehensive examination required before making a definitive diagnosis
for NK- and T-cell neoplasms and broadens the therapeutic options for potential
targets.
PMID- 28695660
TI - A randomized placebo-controlled trial on the effects of Menthacarin, a
proprietary peppermint- and caraway-oil-preparation, on symptoms and quality of
life in patients with functional dyspepsia.
AB - BACKGROUND: Functional dyspepsia (FD) is a very common condition affecting more
than 10% of the population. While there is no cure, a few drugs have been found
to be effective for the relief of symptoms, although most are only effective in a
subgroup of patients. We assess and compare the efficacy of a fixed
peppermint/caraway-oil-combination (Menthacarin) on symptoms and quality of life
(QoL) in patients with FD symptoms consistent with epigastric pain syndrome (EPS)
and postprandial distress syndrome (PDS). METHODS: In a prospective, double
blind, multicenter trial, 114 outpatients with chronic or recurrent FD were
randomized and treated for 4 weeks with the proprietary peppermint- and caraway
oil-preparation Menthacarin or placebo (2*1 capsule/day). Improvement of
abdominal pain and discomfort were used as co-primary efficacy measures (scores
measured with the validated Nepean Dyspepsia Index). KEY RESULTS: After 2 and 4
weeks, active treatment was superior to placebo in alleviating symptoms
consistent with PDS and EPS (P all <.001). After 4 weeks of treatment, pain and
discomfort scores improved by 7.6+/-4.8 and 3.6+/-2.5 points (full analysis set;
mean+/-SD) for Menthacarin and by 3.4+/-4.3 and 1.3+/-2.1 points for placebo,
respectively. All secondary efficacy measures showed advantages for Menthacarin.
CONCLUSIONS & INFERENCES: Menthacarin is an effective therapy for the relief of
pain and discomfort and improvement of disease-specific QoL in patients with FD
and significantly improves symptoms consistent with EPS and PDS.
PMID- 28695661
TI - Relationships between gastric slow wave frequency, velocity, and extracellular
amplitude studied by a joint experimental-theoretical approach.
AB - BACKGROUND: Gastric slow wave dysrhythmias are accompanied by deviations in
frequency, velocity, and extracellular amplitude, but the inherent association
between these parameters in normal activity still requires clarification. This
study quantified these associations using a joint experimental-theoretical
approach. METHODS: Gastric pacing was conducted in pigs with simultaneous high
resolution slow wave mapping (32-256 electrodes; 4-7.6 mm spacing). Relationships
between period, velocity, and amplitude were quantified and correlated for each
wavefront. Human data from two existing mapping control cohorts were analyzed to
extract and correlate these same parameters. A validated biophysically based ICC
model was also applied in silico to quantify velocity-period relationships during
entrainment simulations and velocity-amplitude relationships from membrane
potential equations. KEY RESULTS: Porcine pacing studies identified positive
correlations for velocity-period (0.13 mm s-1 per 1 s, r2 =.63, P<.001) and
amplitude-velocity (74 MUV per 1 mm s-1 , r2 =.21, P=.002). In humans, positive
correlations were also quantified for velocity-period (corpus: 0.11 mm s-1 per 1
s, r2 =.16, P<.001; antrum: 0.23 mm s-1 per 1 s, r2 =.55; P<.001), and amplitude
velocity (94 MUV per 1 mm s-1 , r2 =.56; P<.001). Entrainment simulations matched
the experimental velocity-period relationships and demonstrated dependence on the
slow wave recovery phase. Simulated membrane potential relationships were close
to these experimental results (100 MUV per 1 mm s-1 ). CONCLUSIONS AND
INFERENCES: These data quantify the relationships between slow wave frequency,
velocity, and extracellular amplitude. The results from both human and porcine
studies were in keeping with biophysical models, demonstrating concordance with
ICC biophysics. These relationships are important in the regulation of gastric
motility and will help to guide interpretations of dysrhythmias.
PMID- 28695662
TI - A Readiness Ruler for Assessing Motivation to Change in People with Eating
Disorders.
AB - OBJECTIVE: We examined the psychometric properties of the Eating Disorder
Readiness Ruler a simple self-report instrument designed to enable rapid
assessment of readiness to change problematic eating behaviours in people with
clinical eating disorders. METHOD: We administered the ED-RR, the Eating
Disorders Examination Questionnaire and a measure of autonomous and controlled
motivation for change to 206 individuals receiving outpatient treatment for an
eating disorder. RESULTS: A principal axis factoring analysis of the ED-RR
yielded a significant two-factor solution (explaining 59% of variance)-one factor
pertaining to restriction and body image preoccupation (four items), the other to
binge-eating and vomiting symptoms (two items). The ED-RR showed good internal
consistency (alpha coefficients for the two factors being .77 and .84
respectively). Furthermore, individuals reporting higher readiness showed higher
scores on independent measures of autonomous motivation and greater symptom
reductions over time. DISCUSSION: Results suggest that the ED-RR is a
psychometrically sound tool with potential clinical utility. Copyright (c) 2017
John Wiley & Sons, Ltd and Eating Disorders Association.
PMID- 28695664
TI - Managing fall armyworm, Spodoptera frugiperda (Lepidoptera: Noctuidae), with Bt
maize and insecticides in southern Brazil.
AB - BACKGROUND: Maize plants expressing insecticidal proteins of Bacillus
thuringiensis are valuable options for managing fall armyworm (FAW), Spodoptera
frugiperda, in Brazil. However, control failures were reported, and therefore
insecticides have been used to control this species. Based on these, we evaluated
the use of Bt maize and its integration with insecticides against FAW in southern
Brazil. RESULTS: Early-planted Agrisure TL, Herculex, Optimum Intrasect and non
Bt maize plants were severely damaged by FAW and required up to three
insecticidal sprays. In contrast, YieldGard VT Pro, YieldGard VT Pro 3,
PowerCore, Agrisure Viptera and Agrisure Viptera 3 showed little damage and did
not require insecticides. Late-planted Bt maize plants showed significant damage
by FAW and required up to four sprays, with the exceptions of Agrisure Viptera
and Agrisure Viptera 3. Exalt (first and second sprays); Lannate + Premio (first
spray) and Avatar (second spray); and Karate + Match (first spray) and Ampligo
(second spray) were the most effective insecticides against FAW larvae in Bt and
non-Bt maize. CONCLUSION: Maize plants expressing Cry proteins exhibited FAW
control failures in southern Brazil, necessitating insecticidal sprays. In
contrast, Bt maize containing the Vip3Aa20 protein remained effective against
FAW. However, regardless of the insecticide used against FAW surviving on Bt
maize, grain yields were similar. (c) 2017 Society of Chemical Industry.
PMID- 28695665
TI - Analysis of large 16S rRNA Illumina data sets: Impact of singleton read filtering
on microbial community description.
AB - Next-generation sequencing technologies give access to large sets of data, which
are extremely useful in the study of microbial diversity based on 16S rRNA gene.
However, the production of such large data sets is not only marred by technical
biases and sequencing noise but also increases computation time and disc space
use. To improve the accuracy of OTU predictions and overcome both computations,
storage and noise issues, recent studies and tools suggested removing all single
reads and low abundant OTUs, considering them as noise. Although the effect of
applying an OTU abundance threshold on alpha- and beta-diversity has been well
documented, the consequences of removing single reads have been poorly studied.
Here, we test the effect of singleton read filtering (SRF) on microbial community
composition using in silico simulated data sets as well as sequencing data from
synthetic and real communities displaying different levels of diversity and
abundance profiles. Scalability to large data sets is also assessed using a
complete MiSeq run. We show that SRF drastically reduces the chimera content and
computational time, enabling the analysis of a complete MiSeq run in just a few
minutes. Moreover, SRF accurately determines the actual community diversity: the
differences in alpha- and beta-community diversity obtained with SRF and standard
procedures are much smaller than the intrinsic variability of technical and
biological replicates.
PMID- 28695666
TI - Patient acuity and nurse staffing challenges in Norwegian neonatal intensive care
units.
AB - AIM: To describe fluctuations in patient numbers, patient acuity and the need for
nurses in neonatal intensive care units based on population data. BACKGROUND:
Neonatal intensive care units are difficult to staff appropriately due to
fluctuations in patient volume and acuity. Staffing guidelines have been
developed and applied in some countries to offer the neonatal population safe
patient care. METHOD: National data were used to describe patient load and acuity
for two consecutive years. The need for nurses was calculated by combining these
data with guidelines for nurse staffing. RESULTS: A total of 11.3% of all
neonatal patients in Norway were categorised as intensive care patients. There
were no differences in the need for nurses in weekends vs. weekdays or during
summer holidays vs. days in the rest of the year. Small units have increased
variability in staffing needs, and sufficient staffing is more challenging
compared to that of larger units. CONCLUSION AND IMPLICATIONS FOR NURSING
MANAGEMENT: Planning for reduced staffing for weekends and summer seasons is
ineffective. Staffing planned for most of the days in a year instead of the
median need for nurses will result in a greater increase in the need for nurses
in small units compared to larger units.
PMID- 28695667
TI - A comparison of existing methods for multiple imputation in individual
participant data meta-analysis.
AB - Multiple imputation is a popular method for addressing missing data, but its
implementation is difficult when data have a multilevel structure and one or more
variables are systematically missing. This systematic missing data pattern may
commonly occur in meta-analysis of individual participant data, where some
variables are never observed in some studies, but are present in other
hierarchical data settings. In these cases, valid imputation must account for
both relationships between variables and correlation within studies. Proposed
methods for multilevel imputation include specifying a full joint model and
multiple imputation with chained equations (MICE). While MICE is attractive for
its ease of implementation, there is little existing work describing conditions
under which this is a valid alternative to specifying the full joint model. We
present results showing that for multilevel normal models, MICE is rarely exactly
equivalent to joint model imputation. Through a simulation study and an example
using data from a traumatic brain injury study, we found that in spite of
theoretical differences, MICE imputations often produce results similar to those
obtained using the joint model. We also assess the influence of prior
distributions in MICE imputation methods and find that when missingness is high,
prior choices in MICE models tend to affect estimation of across-study
variability more than compatibility of conditional likelihoods. Copyright (c)
2017 John Wiley & Sons, Ltd.
PMID- 28695668
TI - A Nitrile Glucoside and Biflavones from the Leaves of Campylospermum excavatum
(Ochnaceae).
AB - The study of the MeOH extract of the leaves of Campylospermum excavatum led to
the isolation of a nitrile glucoside, named campyloside C (1) and an original
derivative of ochnaflavone, 7-O-methylochnaflavone (2), along with three known
biflavonoids, amentoflavone, sequoiaflavone, and sotetsuflavone (3 - 5). The
linkage site of the sub-units of 2 was confirmed by chemical correlation, after
semi-synthesis of a trimethoxylated derivative of ochnaflavone (2a). The
structures of these compounds as well as their relative and absolute
configurations were assigned by 1D- and 2D-NMR experiments, HR-ESI-MS and
Electronic Circular Dichroism (ECD) calculations. A low-pass J filter HMBC
experiment was performed in order to define the configuration of the double bond
of 1. All of the biflavonoids were evaluated against protozoan parasites.
Amentoflavone moderately inhibited the promastigote form of Leishmania infantum.
PMID- 28695669
TI - Risk estimation for biliary tract cancer: Development and validation of a
prognostic score.
AB - BACKGROUND & AIMS: Biliary tract cancer is a rare tumour entity characterized by
a poor prognosis. We aimed to identify prognostic factors and create a prognostic
score to estimate survival. METHODS: Clinical data of the training set,
consisting of 569 patients treated from 2000 to 2010 at Hannover Medical School,
were analysed. A prognostic model defining three prognostic risk groups was
derived from Cox regression analyses. The score was applied and validated in an
independent cohort of 557 patients from four different German centres. RESULTS:
Median overall survival (OS) was 14.5 months. If complete resection was
performed, the patients had a significantly improved OS (23.9 months; n=242) as
compared to patients with non-resectable tumours (9.1 months; n=329, P<.0001).
Based on univariable and multivariable analyses of clinical data, a prognostic
model was created using variables available before treatment. Those were age,
metastasis, C-reactive protein (CRP), international normalized ratio (INR) and
bilirubin. The prognostic score distinguished three groups with a median OS of
21.8, 8.6 and 2.6 months respectively. The validation cohort had a median OS of
20.2, 14.0 and 6.5 months respectively. The prognostic impact of the score was
independent of the tumour site and of treatment procedures. CONCLUSIONS: Here, we
identified prognostic factors and propose a prognostic score to estimate
survival, which can be applied to all patients independent of tumour site and
before initial treatment. Further validation in prospective trials is required.
PMID- 28695670
TI - Mitochondrial dysfunction and cerebral metabolic abnormalities in patients with
mitochondrial encephalomyopathy subtypes: Evidence from proton MR spectroscopy
and muscle biopsy.
AB - AIMS: Accumulated evidence indicates that cerebral metabolic features, evaluated
by proton magnetic resonance spectroscopy (1 H-MRS), are sensitive to early
mitochondrion dysfunction associated with mitochondrial encephalomyopathy (ME).
The metabolite ratios of lactate (lac)/Cr, N-acetyl aspartate (NAA)/creatine
(Cr), total choline (tCho)/Cr, and myoinositol (mI)/Cr are measured in the
infarct-like lesions by 1 H-MRS and may reveal metabolic changes associated with
ME. However, the application of this molecular imaging technique in the
investigation of the pathology of ME subtypes is unknown. METHODS: In this study,
cerebral metabolic features of pathologically diagnosed ME cases, that is, 19
mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes
(MELAS); nine chronic progressive external ophthalmoplegia (CPEO); and 23 healthy
controls, were investigated using 1 H-MRS. Receiver operating characteristics
(ROC) analysis was used to evaluate the diagnostic power of the cerebral
metabolites. Histochemical evaluation was carried out on muscle tissues derived
from biopsy to assess the abnormal mitochondrial proliferation. The association
between cerebral metabolic and mitochondrial cytopathy was examined by
correlation analysis. RESULTS: Patients with MELAS or CPEO exhibited a
significantly higher Lac/Cr ratio and a lower NAA/Cr ratio compared with
controls. The ROC curve of Lac/Cr ratio indicated prominent discrimination
between MELAS or CPEO and healthy control subjects, whereas the NAA/Cr ratio may
present diagnostic power in the distinction of MELAS from CPEO. Lower NAA/Cr
ratio was associated with higher Lac/Cr in MELAS, but not in CPEO. Furthermore,
higher ragged-red fibers (RRFs) percentages were associated with elevated Lac/Cr
and reduced NAA/Cr ratios, notably in MELAS. This association was not noted in
the case of mI/Cr ratio. CONCLUSIONS: Mitochondrial cytopathy (lactic acidosis
and RRFs on muscle biopsy) was associated with neuronal viability but not glial
proliferation, notably in MELAS. Mitochondrial neuronopathy and neuronal
vulnerability are considered significant causes in the pathogenesis of MELAS,
particularly with regard to stroke-like episodes.
PMID- 28695671
TI - Duodenal duplication cyst causing recurrent pancreatitis.
PMID- 28695672
TI - Developmental delays in emotion regulation strategies in preschoolers with
autism.
AB - : Children with autism spectrum disorder (ASD) commonly present with difficulty
regulating negative emotions, which has been found to impact their behavioral and
mental health. Little research has documented the strategies that children with
ASD use to regulate their emotion to understand whether they use qualitatively
different strategies to children without ASD, whether these are developmentally
delayed, or both. Forty-four children with ASD and 29 typically-developing
children (2-4 years) were given tasks designed to mimic everyday life experiences
requiring children to manage low-level stress (e.g., waiting for a snack) and
children's emotion regulation strategies were coded. Parents reported on their
child's mental health, wellbeing, and self-development. The results suggest
differences in using emotion regulation strategies in children with ASD,
reflecting a delay, rather than a deviance when compared to those used by
children without ASD. Only children with ASD relied on their family members for
physical and communicative soothing; the typically developing children relied on
people outside of their family for help regulating their emotion. More frequent
approach/less frequent avoidance was related to a higher self-evaluation in both
groups, but was only additionally related to higher self-recognition and autonomy
in the ASD group. These findings help to identify important emotion regulation
intervention targets for this population, including supporting communication with
people outside of the family and independence. Autism Res 2017, 10: 1808-1822.
(c) 2017 International Society for Autism Research, Wiley Periodicals, Inc. LAY
SUMMARY: Results suggest that children with autism had more difficulty using
communication strategies to manage stress only with people outside the family;
they used these strategies with family members as often as children without
autism. For all children, more task approach/less avoidance was related to
children's higher self-evaluation. These findings suggest targeting communication
with people outside of the family and personality development as appropriate
intervention goals.
PMID- 28695673
TI - Gene polymorphism and HLA-G expression in patients with childhood-onset systemic
lupus erythematosus: A pilot study.
AB - Human leukocyte antigen-G (HLA-G) presents inhibitory functions in immune cells
and is located in a chromosomal region associated with systemic lupus
erythematosus (SLE) susceptibility. Polymorphisms in 3' untranslated region
(3'UTR) of HLA-G gene may influence protein expression. To date, no study
analyzing HLA-G polymorphism and expression in childhood-onset systemic lupus
erythematosus (cSLE) has been conducted. Therefore, we investigated the influence
of HLA-G 3'UTR polymorphisms in 50 cSLE patients and 144 healthy controls. For
the expression analysis, the control group included 26 healthy individuals. No
significant difference in allele, genotype, and haplotype frequencies was
observed between patients and control group. However, both the 14 bp deletion
allele (odds ratio [OR] = 2.76, 95% confidence interval [CI] = 1.17-6.52, P =
.028) and the 14 bp deletion-deletion genotype (OR = 8.00, 95% CI = 1.57-40.65, P
= .006) showed an association with lupus nephritis. After Bonferroni correction,
none P-value remained statistically significant. Regarding HLA-G expression, no
significant difference was observed between plasma levels of cSLE patients (56.02
U/mL, interquartile range [IQR] = 37.54-75.41) and control group (49.2 U/mL, IQR
= 27.84-154.4, P = .952). However, when the patients were stratified according to
clinical manifestations, patients with hematological manifestations showed a
lower plasma concentration of soluble HLA-G (sHLA-G) (47.08 U/mL, IQR = 34.15
61.56) than patients with no hematological manifestations (65.26 U/mL, IQR =
47.69-102.60, P = .013). These results suggest that HLA-G polymorphism has small
effect on cSLE susceptibility and that sHLA-G may be involved in the pathogenesis
of the disease.
PMID- 28695674
TI - Foetal pulmonary maturity in dogs: Estimated from bubble tests in amniotic fluid
obtained via amniocentesis.
AB - The goal of this study was to evaluate the reliability of amniocentesis during
late pregnancy to assess lung maturity in puppies using a bubble test as
described by Gunston and Davey (South African Medical Journal, 54, 1978, 495).
Thirty-five bitches from eight different breeds were followed during late
pregnancy before undergoing elective Caesarean (C)-section on days 61-62 after
ovulation. Bubble tests were performed the day before the C-section (n = 11
bitches) and before the administration of aglepristone on amniotic fluid samples
obtained via amniocentesis and were repeated the day of the surgery on amniotic
fluid samples collected via puncture of the amniotic bags before they were opened
(n = 35 bitches). No complications were observed following amniocenteses and the
C-sections. The mortality rate (2.3%) was similar to the result of other studies
using the same protocol for an elective C-section. Of the non-contaminated
samples collected the day of the C-section, 89.6% were positive in the bubble
test, which was consistent with observations of clinical maturity the day of the
surgery and on the following days. In contrast, 70% of the samples collected the
day before the C-section (when progesterone concentrations were still high) were
negative, suggesting that the puppies were still immature at this point in the
pregnancy. Additionally, we observed a significant difference in the bubble test
results before and 18 hr after the administration of aglepristone, suggesting
that aglepristone may act as an inducer of the final maturation of the puppies by
inactivating progesterone receptors and simulating a physiological decrease in
progesterone. Finally, we confirmed the need to exclude all contaminated samples,
which could lead to false-negative results.
PMID- 28695675
TI - The role of diffusion-weighted imaging in prediction liver iron concentration in
beta-thalassaemia patients.
AB - OBJECTIVE: The aim of this study was to analyse the value of diffusion-weighted
magnetic resonance imaging (DWI) to determine the liver parenchyma iron
concentration in beta-thalassaemia major patients. METHODS: Abdominal magnetic
resonance (MR) imaging, including gradient echo sequences and DWI sequences, was
undertaken of 55 beta-thalassaemia major patients. The apparent diffusion
coefficient (ADC) values of liver parenchyma were measured in seven regions at
the level of the portal bifurcation and compared with liver iron concentration
(LIC). Patients with normal and mild liver dry weight (LDW) results were
classified as group 1, whereas patients with moderate and severe values were
classified as group 2. RESULTS: There was a dramatic decrease in ADC values as
the severity of LIC increased. The median ADC values were 1.6-1.9 * 10-3 mm2
/sec in group 1 and 0.6-0.9 * 10-3 mm2 /sec in group 2. A negative correlation
was observed between ADC and the LDW values in both groups. The ADC and LIC
correlation in each subgroup was statistically significant with asymptotic 95%
confidence intervals of 0.820-0.997. CONCLUSION: Diffusion-weighted imaging is
sensitive to tissue changes as a result of iron accumulation and may be used to
predict liver iron overload in beta-thalassaemia major patients with a high
sensitivity and specificity.
PMID- 28695676
TI - Matrin3 binds directly to intronic pyrimidine-rich sequences and controls
alternative splicing.
AB - Matrin3 is an RNA-binding protein that is localized in the nuclear matrix.
Although various roles in RNA metabolism have been reported for Matrin3, in vivo
target RNAs to which Matrin3 binds directly have not been investigated
comprehensively so far. Here, we show that Matrin3 binds predominantly to
intronic regions of pre-mRNAs. Photoactivatable Ribonucleoside-Enhanced Cross
linking and Immunoprecipitation (PAR-CLIP) analysis using human neuronal cells
showed that Matrin3 recognized pyrimidine-rich sequences as binding motifs,
including the polypyrimidine tract, a splicing regulatory element. Splicing
sensitive microarray analysis showed that depletion of Matrin3 preferentially
increased the inclusion of cassette exons that were adjacent to introns that
contained Matrin3-binding sites. We further found that although most of the genes
targeted by polypyrimidine tract binding protein 1 (PTBP1) were also bound by
Matrin3, Matrin3 could control alternative splicing in a PTBP1-independent
manner, at least in part. These findings suggest that Matrin3 is a splicing
regulator that targets intronic pyrimidine-rich sequences.
PMID- 28695677
TI - Combined genetic analyses can achieve efficient diagnostic yields for subjects
with Alagille syndrome and incomplete Alagille syndrome.
AB - AIM: We evaluated combined genetic analyses with targeted next-generation
sequencing (NGS), multiplex ligation probe amplification (MLPA) of Jagged1 (JAG1)
genes and microarray comparative genomic hybridisation (CGH) in subjects with
Alagille syndrome, incomplete clinical features of Alagille syndrome and biliary
atresia. METHODS: Subjects recruited from April 2013 to December 2015 underwent a
targeted NGS analysis, including JAG1 and Notch homolog 2 (NOTCH2). If no
mutations were detected in JAG1 or NOTCH2, or if copy number variations were
suggested by the NGS analysis, we performed an MLPA analysis of JAG1. We also
performed a microarray CGH analysis with whole-exon deletion detected by the MLPA
analysis. RESULTS: We analysed 30 subjects with Alagille syndrome, nine with
incomplete Alagille syndrome and 17 with biliary atresia and detected pathogenic
mutations in JAG1 or NOTCH2 in 24/30 subjects with Alagille syndrome and in 4/9
subjects with incomplete Alagille syndrome. No pathogenic mutations were detected
in subjects with biliary atresia. The frequency of JAG1 mutations was as follows:
single nucleotide variants (51.9%), small insertion or deletion (29.6%) and gross
deletion (18.5%). CONCLUSION: Combined genetic analyses achieved efficient
diagnostic yields for subjects with Alagille syndrome and incomplete Alagille
syndrome.
PMID- 28695678
TI - Would the real arsenate reductase please stand up?
PMID- 28695679
TI - John R. Stinchcombe.
PMID- 28695680
TI - Insights into the historical assembly of East Asian subtropical evergreen
broadleaved forests revealed by the temporal history of the tea family.
AB - Subtropical evergreen broadleaved forests (EBLFs) inhabit large areas of East
Asia. Although paleovegetation reconstructions have revealed that the subtropical
EBLFs existed in Southwest China during the Miocene, the historical construction
of these forests remains poorly known. Here, we used the tea family (Theaceae), a
characteristic component of the subtropical EBLFs, to gain new insights into the
assembly of this important biome. Using a robust phylogenetic framework of
Theaceae based on plastome and nuclear ribosomal DNA sequence data, the temporal
history of the family was reconstructed. Data from other characteristic
components of subtropical EBLFs, including Fagaceae, Lauraceae and Magnoliaceae,
were also integrated. Most of the essential elements of the subtropical EBLFs
appear to have originated around the Oligocene-Miocene (O-M) boundary. However,
small woody lineages (e.g. Camellia, Hartia) from Theaceae were dated to the late
Miocene. Accelerated net diversification rates within Theaceae were also detected
near the O-M transition period and the late Miocene. Our results suggest that two
independent intensifications of the East Asian summer monsoon (EASM) around the O
M boundary and the late Miocene may have facilitated the historical assembly of
the subtropical EBLFs in East Asia.
PMID- 28695681
TI - Bi-directional COS exchange in bryophytes challenges its use as a tracer for
gross primary productivity.
PMID- 28695682
TI - Biodiversity as a solution to mitigate climate change impacts on the functioning
of forest ecosystems.
AB - Forest ecosystems are critical to mitigating greenhouse gas emissions through
carbon sequestration. However, climate change has affected forest ecosystem
functioning in both negative and positive ways, and has led to shifts in
species/functional diversity and losses in plant species diversity which may
impair the positive effects of diversity on ecosystem functioning. Biodiversity
may mitigate climate change impacts on (I) biodiversity itself, as more-diverse
systems could be more resilient to climate change impacts, and (II) ecosystem
functioning through the positive relationship between diversity and ecosystem
functioning. By surveying the literature, we examined how climate change has
affected forest ecosystem functioning and plant diversity. Based on the
biodiversity effects on ecosystem functioning (B->EF), we specifically address
the potential for biodiversity to mitigate climate change impacts on forest
ecosystem functioning. For this purpose, we formulate a concept whereby
biodiversity may reduce the negative impacts or enhance the positive impacts of
climate change on ecosystem functioning. Further B->EF studies on climate change
in natural forests are encouraged to elucidate how biodiversity might influence
ecosystem functioning. This may be achieved through the detailed scrutiny of
large spatial/long temporal scale data sets, such as long-term forest
inventories. Forest management strategies based on B->EF have strong potential
for augmenting the effectiveness of the roles of forests in the mitigation of
climate change impacts on ecosystem functioning.
PMID- 28695683
TI - Combinations of single nucleotide polymorphisms WWOX-rs13338697, GALNT14
rs9679162 and rs6025211 effectively stratify outcomes of chemotherapy in advanced
hepatocellular carcinoma.
AB - AIM: A genome-wide association study (GWAS) had identified a single nucleotide
polymorphism (SNP), GALNT14-rs9679162, capable of predicting chemotherapy
responses in advanced hepatocellular carcinoma (HCC). Here, we revisited the GWAS
database to search for necessary SNPs that could improve our outcome prediction.
METHODS: A cohort of 116 HCC patients receiving split-dose chemotherapy composed
of 5-fluorouracil, mitoxantrone and cisplatin was enrolled. The GALNT14-rs9679162
together with four other leading candidate SNPs (rs6025211, rs715171,
LOC105369482-rs1955024 and WWOX-rs13338697) was genotyped and correlated with
time-to-tumor progression (TTP) and overall survival (OS). RESULTS: GALNT14
rs9679162-TT genotype remained an effective predictor for favorable TTP and OS (P
= 0.012 and 0.002). Additionally, it was found that WWOX-rs13338697-CT genotype
was associated with unfavorable TTP (P = 0.031), independent of GALNT14-rs9679162
genotype (adjusted P = 0.045), and rs6025211-CT genotype was associated with
unfavorable OS (P = 0.014), independent of GALNT14-rs9679162 genotype (adjusted P
= 0.025). Combinations of these SNPs stratified patients into three groups with
differential treatment outcomes. Patients with GALNT14-rs9679162-TT/WWOX
rs13338697-non-CT genotypes achieved the most favorable treatment outcomes (n =
19; median TTP, median OS and response rate were 3.9 months, 6.8 months and 4/19
[21.1%], respectively); whereas patients with GALNT14-rs9679162-non-TT/rs6025211
CT genotypes associated with the most unfavorable treatment outcomes (n = 40;
median TTP, median OS and response rate were 1.9 months, 3.5 months and 1/40
[2.5%], respectively). The remaining patients constituted a third subgroup with
intermediate clinical outcomes. CONCLUSIONS: Three genetic variants, GALNT14
rs9679162, WWOX-rs13338697 and rs6025211, stratified advanced HCC patients into
three groups with differential treatment outcomes.
PMID- 28695684
TI - The pitfalls of qualified moral veganism. A critique of Jan Deckers' holistic
health approach to animal ethics.
AB - I critically examine Jan Deckers' position in Animal (De)liberation, where he
defends two main views. The first is "qualified moral veganism": Most humans have
a duty to abstain from consuming animal products, even if there are circumstances
in which doing so is justified. The author argues, on the one hand, from a pan
sentientist view that attributes sentience to all elementary entities and their
compounds. Thus, all living things (such as animals and plants) have a capacity
for positive and negative experiences. On the other hand, he develops a
consequentialist view that assigns moral agents the unconditional duty to promote
their own "holistic health." This is partly constituted by the agent's "moral
health," that is, her acting in a morally justified way. On Deckers' view, moral
agents must care for the health of all living entities, give greater weight to
the interests of organisms to which they are more closely biologically related,
and respect the integrity of nature. Diets containing animal products have a very
high negative health impact, because of how they affect the environment, human
food security, and the well-being of nonhuman animals. In addition, even though
plants are sentient, they are likely less so than animals, and their interests
must be given less weight. Therefore, most humans should shift to a vegan diet.
Deckers' second proposal is that a qualified ban on the consumption of animal
products should be enacted. After discarding other alternative strategies,
Deckers defends its feasibility relying on data obtained via a series of surveys.
Though the argument partly succeeds in developing a coherent account
accommodating the author's intuitions, I conclude that his ontological and
normative frameworks remain too underdeveloped, his appeal to biological
relatedness has implausible implications, and the methodology he uses in defence
of his political position is problematic.
PMID- 28695685
TI - Diet quality and sleep quality among day and night shift nurses.
AB - AIMS: To determine whether night shift workers have a poorer diet quality and
sleep quality when compared with day shift nurses. BACKGROUND: There is a dearth
of research investigating the association between diet quality and sleep quality
of day and night shift nurses. METHODS: Data on nurses (n = 103) working either a
day or night shift from two Midwestern hospitals were obtained from August 2015
to February 2016. The instruments used were the Diet History Questionnaire and
the Pittsburg Sleep Quality Index. Independent samples t-tests were used to
examine differences in diet and sleep quality by work shift schedule. RESULTS:
There were no statistically significant differences between nurses working day or
night shift and sleep quality (P = 0.0684), as well as diet quality (P = 0.6499).
There was a significant difference between both body mass index (P = 0.0014) and
exercise (P = 0.0020) with regard to diet quality. Body mass index and sleep
quality were also significantly associated (P = 0.0032). CONCLUSION: Our study
found no differences between day and night shift with regard to sleep and diet
quality among nurses. IMPLICATIONS FOR NURSING MANAGEMENT: Deliberate health
initiatives and wellness programmes specifically targeting nurses are needed to
increase knowledge about maintaining a healthy lifestyle while working as a
nurse, whether it is day or night shift.
PMID- 28695686
TI - Imprint cytology of clear cell sarcoma-like tumor of the gastrointestinal tract
in the small intestine: A case report.
AB - Clear cell sarcoma-like tumor of the gastrointestinal tract (CCSLGT) is an
extremely rare malignant neoplasm in the digestive tract. Its cytomorphologic
features have never previously been reported. Here, we describe a case of CCSLGT,
including its cytologic examination findings. A 47-year-old woman presented with
a mass in the small intestine, which was resected and sent for imprint cytology.
Imprint smears revealed tumor cells with light eosinophilic or clear cytoplasm in
a necrotic background. Many of the tumor cells were arranged in a perivascular
growth with a pseudopapillary formation, and there were some non-neoplastic
osteoclast-like giant cells. Histological examination revealed solid nests and a
pseudopapillary pattern of the tumor cells with clear or pale eosinophilic
cytoplasm and large nuclei with small nucleoli. Immunohistochemistry showed
positive for vimentin, S-100, and SOX-10, and negative for SMA, c-KIT,
cytokeratin, HMB-45, and MelanA. The EWSR1 gene split signal was detected by
reverse transcriptase fluorescence in situ hybridization, and EWSR1-CREB1 gene
fusion was indicated by reverse transcriptase polymerase chain reaction analysis.
From these findings, we diagnosed the tumor as CCSLGT. To best of our knowledge,
this is the first description of the imprint cytology features of CCSLGT.
PMID- 28695687
TI - Electro-fermentation triggering population selection in mixed-culture glycerol
fermentation.
AB - Electro-fermentation is a new technique that could be used to influence the
global metabolism in mixed-culture fermentation. In this study, a mixed-culture
cathodic electro-fermentation of glycerol was investigated. Both microbial
community structure and metabolic patterns were altered when compared to standard
fermentation. This microbial population shift was more significant when the
working electrodes were pre-colonized by Geobacter sulfurreducens, before electro
fermentation. The electro-fermenting microbial community was more efficient for
producing 1,3-propanediol with an improved yield of 10% when compared with
fermentation controls. Such improvement did not require high energy and total
electron input represented < 1% of the total electron equivalents provided only
by glycerol. A linear model was developed to estimate the individual metabolic
pattern of each operational taxonomic unit. Application of this model compared to
the experimental results suggests that the changes in global metabolism were
supported by bacterial population selection rather than individual metabolism
shift. This study shows for the first time that both fermentation pattern and
bacterial community composition can be influenced by electro-fermentation
conditions.
PMID- 28695688
TI - Opening Pandora's box?: ethical issues in prenatal whole genome and exome
sequencing.
AB - OBJECTIVE: The development of genomic approaches to prenatal testing such as
whole genome and exome sequencing offers the potential for a better understanding
of prenatal structural anomalies in the fetus and ultimately for improved patient
care and more informed reproductive decision making. In addition to the
scientific and clinical challenges of achieving this, the introduction of new
reproductive technologies also presents a number of ethical problems. The
successful and appropriate development and introduction of prenatal genomics into
clinical practice require these problems to be identified, understood and
carefully analysed in the development of models of good ethical practice. METHOD:
We conducted a critical review of the existing literature on ethical issues in
prenatal genomics. RESULTS: We identified and discussed five areas of particular
concern: valid consent, management and feed-back of information, responsibilities
of health professionals, priority setting and resources and duties towards the
future child. CONCLUSION: There is a need for further discussion of the issues we
have outlined here, and we hope that this brief summary of ethical arguments in
the literature encourages researchers, clinicians, patients and scientists to
engage in further discussion of these and other important issues raised by
prenatal genomics. (c) 2017 The Authors. Prenatal Diagnosis published by John
Wiley & Sons, Ltd.
PMID- 28695689
TI - Patterns of health services utilization in the last two weeks of life among
cancer patients: Experience in an Australian academic cancer center.
AB - AIM: To report the trend in end-of-life health services (HS) utilization among
cancer patients treated in a large Australian academic cancer center over a 12
year period. METHODS: This is a retrospective study of cancer patients treated at
the Peter MacCallum Cancer Centre (PMCC), who had documented death between
January 2002 and December 2013. Using administrative and billing database, we
report on the utilization of different categories of HS within two weeks of
death: diagnostic investigations (pathology and radiology), inpatient and
outpatient services, and potentially futile interventions (PFI, which include
radiotherapy, chemotherapy and surgery). RESULTS: Of the 27 926 "active" cancer
patients in the study (i.e. those with medical contact at PMCC in the last year
of life), 6368 (23%) had documented HS utilization within two weeks of death. 11%
and 9% had pathology and radiology investigations respectively, 14% had
outpatient clinic appointments, and 7% had hospital admissions. There were 2654
patients (10%) who had PFI within two weeks of death - 2198 (8%) had
radiotherapy, 287 (1%) chemotherapy and 267 (1%) surgery. We observed peak HS and
PFI utilization in 2004, which then dropped to its lowest in 2009/2010.
CONCLUSION: Experience in an Australian cancer center suggests approximately one
in four "active" cancer patients had HS utilization, and one in ten had PFI,
within two weeks of death. The implementation of palliative care guidelines may
reduce some of these potentially wasteful and futile interventions.
PMID- 28695690
TI - Cerebral vasospasm in acute porphyria.
AB - BACKGROUND AND PURPOSE: Porphyrias are a group of inherited metabolic disorders
resulting from a specific deficiency along the pathway of haem biosynthesis. A
clinical classification distinguishes acute from non-acute porphyrias considering
the occurrence of life-threatening neurovisceral attacks, presenting with
abdominal pain, neuropsychiatric disturbance and neuropathy. Vasospasm is a very
rare complication that can occur in all major types of acute porphyria. METHODS:
We describe a porphyric crisis with vasospasm in a woman with previously
undiagnosed acute porphyria. Furthermore we performed a systematic review by
searching the electronic database Pubmed/MEDLINE for additional data in published
studies of vasospasm in acute porphyria. RESULTS: Overall, 9 case reports
reporting on 11 patients who suffered vasospasm during an exacerbation of acute
porphyria were identified. All of the reported patients were women and the mean
age was 29.4 years. When brain MRI was performed, T2-hyperintense lesions,
consistent with ischaemic changes, were observed in most patients (10/11, 91%).
Although the genetic pathogenesis of the disease is well understood, the precise
mechanisms to explain neurologic involvement in acute porphyria remain unclear.
CONCLUSION: Acute porphyria is an unusual and rare cause of vasospasm. However,
considering porphyria in patients with unexplained cerebral vasospasm, especially
in women of childbearing age, is crucial given the severity of possible
complications and the available treatment options.
PMID- 28695691
TI - Neonatal therapeutic hypothermia outside of standard guidelines: a survey of U.S.
neonatologists.
AB - AIM: Therapeutic hypothermia is standard of care in term infants with moderate-to
severe hypoxic-ischaemic encephalopathy (HIE). The goal of this survey was to
explore the attitudes of U.S. neonatologists caring for infants with HIE who fall
outside of current guidelines. METHODS: Case-based survey administered to members
of the Section on Neonatal-Perinatal Medicine of the American Academy of
Pediatrics. RESULTS: A total of 447 responses were analysed, a response rate of
19%. We found significant variability amongst U.S. neonatologists with regard to
the use of therapeutic hypothermia for infants with HIE who fall outside standard
inclusion criteria. Scenarios with the most variability included HIE in a late
preterm infant and HIE following a postnatal code. Provision of therapeutic
hypothermia outside of standard guidelines was not influenced by number of years
in practice, neonatal intensive care type (NICU) or NICU size. CONCLUSION:
Significant variability in practice exists when caring for infants with HIE who
do not meet standard inclusion criteria, emphasizing the need for continued and
rigorous research in this area.
PMID- 28695698
TI - Identifying children at risk for language impairment: screening of communication
at 18 months Reply.
PMID- 28695703
TI - A cross-sectional study investigating patient-centred care, co-creation of care,
well-being and job satisfaction among nurses.
AB - BACKGROUND: Developments in the community health nursing sector have resulted in
many changes in the activities of these nurses. The concepts of patient-centred
care and co-creation of care are gaining importance in the work of community
health nurses. Whether patient-centred care also contributes positively to
nurses' well-being and job satisfaction is not known. METHOD: In 2015, a cross
sectional survey was conducted among 153 community health nurses employed by 11
health care organisations in the southern part of the Netherlands. Correlation
and regression analyses were performed to identify relationships among patient
centred care, co-creation of care, background characteristics, job satisfaction
and well-being of community health nurses. RESULTS: Patient-centred care and co
creation of care were correlated positively with community health nurses' well
being and job satisfaction. Both variables were predictors of well-being, and
patient-centred care was a predictor of job satisfaction. The length of time in
the present position was related negatively to community health nurses' job
satisfaction and well-being. CONCLUSIONS: Investment in patient-centred care and
co-creation of care is important for the well-being and job satisfaction of
community health nurses. IMPLICATIONS FOR NURSING MANAGEMENT: To safeguard or
improve job satisfaction and well-being of community health nurses, organisations
should pay attention to the co-creation of care and patient-centred care.
PMID- 28695704
TI - Dermoscopy of syringocystadenoma papilliferum.
AB - Syringocystadenoma papilliferum is a benign adnexal neoplasm frequently seen in
association with other adnexal tumours. We report the dermoscopic features of
three cases of syringocystadenoma papilliferum developing in naevus sebaceus.
Clinically the lesions were characterised by exophytic papillary structures.
Dermoscopically, polymorphous vessels were the prevalent feature.
PMID- 28695705
TI - All drinking is not equal: how a social practice theory lens could enhance public
health research on alcohol and other health behaviours.
AB - BACKGROUND: The social meanings, settings and habitual nature of health-related
activities and their integration into our daily lives are often overlooked in
quantitative public health research. This reflects an overly individualized
approach to epidemiological surveillance and evaluations of public health
interventions, based on models of behaviour that are rooted in social cognition
and rational choice theories. This paper calls for a new approach to alcohol
epidemiology and intervention research informed by theories of practice.
ARGUMENT: Practices are conceptualized as routinized types of human activity that
are made up of, and can be recognized by, the coming together of several
interwoven elements in the same situation (e.g. materials, meanings, skills,
locations, timings). Different practices are interconnected-they can occur
simultaneously (e.g. drinking and eating), hold each other in place (e.g. after
work drinks) or compete for time (e.g. parenting versus socializing). Applying
these principles to alcohol research means shifting attention away from
individuals and their behaviours and instead making drinking practices an
important unit of analysis. Studying how drinking practices emerge, persist and
decay over time, how they spread through populations and local or social networks
and how they relate to other activities of everyday life promises new insights
into how, why, where, when and with whom drinking and getting drunk occur.
CONCLUSIONS: Theories of practice provide a framework for generating new
explanations of stability and change in alcohol consumption and other health
behaviours. This framework offers potential for novel insights into the
persistence of health inequalities, unanticipated consequences of policies and
interventions and new interventions targets through understanding which elements
of problematic practices are likely to be most modifiable. We hope this will
generate novel insights into the emergence and decay of drinking practices over
time and into the geographical and socio-demographic patterning of drinking.
Theories of practice-informed research would consider how alcohol policies and
population-level interventions might differentially affect different drinking
practices.
PMID- 28695706
TI - Seasonal associations with urban light pollution for nocturnally migrating bird
populations.
AB - The spatial extent and intensity of artificial light at night (ALAN) has
increased worldwide through the growth of urban environments. There is evidence
that nocturnally migrating birds are attracted to ALAN, and there is evidence
that nocturnally migrating bird populations are more likely to occur in urban
areas during migration, especially in the autumn. Here, we test if urban sources
of ALAN are responsible, at least in part, for these observed urban associations.
We use weekly estimates of diurnal occurrence and relative abundance for 40
nocturnally migrating bird species that breed in forested environments in North
America to assess how associations with distance to urban areas and ALAN are
defined across the annual cycle. Migratory bird populations presented stronger
than expected associations with shorter distances to urban areas during
migration, and stronger than expected association with higher levels of ALAN
outside and especially within urban areas during migration. These patterns were
more pronounced during autumn migration, especially within urban areas. Outside
of the two migration periods, migratory bird populations presented stronger than
expected associations with longer distances to urban areas, especially during the
nonbreeding season, and weaker than expected associations with the highest levels
of ALAN outside and especially within urban areas. These findings suggest that
ALAN is associated with higher levels of diurnal abundance along the boundaries
and within the interior of urban areas during migration, especially in the autumn
when juveniles are undertaking their first migration journey. These findings
support the conclusion that urban sources of ALAN can broadly effect migratory
behavior, emphasizing the need to better understand the implications of ALAN for
migratory bird populations.
PMID- 28695707
TI - Comparison of long-term clinical outcomes among different vascularized lymph node
transfers: 6-year experience of a single center's approach to the treatment of
lymphedema.
AB - BACKGROUND: This study evaluated the long-term clinical outcomes among different
vascularized lymph node transfers (VLNT) used at our institution. METHODS:
Between July 2010 and July 2016, all patients with International Society of
Lymphology (ISL) stages II-III who underwent VLNT were evaluated. Demographic and
clinical data (limb circumference, infectious episodes, lymphoscintigraphic
studies) were recorded pre-operatively. Clinical outcomes, complications, and
additional excisional procedures were analyzed post-operatively. At least 2-year
follow-up was required for inclusion. RESULTS: Overall, 83 patients (Stage II:47,
Stage III:36) met the inclusion criterion. Mean follow-up was 32.8 months (range,
24-49). Lymph node flaps used were groin (n = 13), supraclavicular (n = 25),
gastroepiploic (n = 42), ileocecal (n = 2), and appendicular (n = 1). Total mean
circumference reduction rate was 29.1% (Stage II) and 17.9% (Stage III) (P <
0.05). A paired t-test showed that VLNT significantly decreased the number of
infections (P < 0.05). Three patients reported no improvement of the symptoms.
Major complications included one flap loss and one donor site hematoma. After the
period of follow-up, 18 patients (21.7%) underwent additional excisional
procedures. CONCLUSION: VLNT is a promising technique used for the treatment of
lymphedema and appears to be more effective in moderate stages (Stage II).
Patients with advanced stage lymphedema (Stage III) may benefit from additional
excisional procedures.
PMID- 28695708
TI - Targeting fatty acid amide hydrolase and transient receptor potential vanilloid-1
simultaneously to modulate colonic motility and visceral sensation in the mouse:
A pharmacological intervention with N-arachidonoyl-serotonin (AA-5-HT).
AB - BACKGROUND: Endocannabinoid anandamide (AEA) inhibits intestinal motility and
visceral pain, but it may also be proalgesic through transient receptor potential
vanilloid-1 (TRPV1). AEA is degraded by fatty acid amide hydrolase (FAAH). This
study explored whether dual inhibition of FAAH and TRPV1 reduces diarrhea and
abdominal pain. METHODS: Immunostaining was performed on myenteric plexus of the
mouse colon. The effects of the dual FAAH/TRPV1 inhibitor AA-5-HT on electrically
induced contractility, excitatory junction potential (EJP) and fast (f) and slow
(s) inhibitory junction potentials (IJP) in the mouse colon, colonic propulsion
and visceromotor response (VMR) to rectal distension were studied. The colonic
levels of endocannabinoids and fatty acid amides were measured. KEY RESULTS: CB1
positive neurons exhibited TRPV1; only some TRPV1 positive neurons did not
express CB1. CB1 and FAAH did not colocalize. AA-5-HT (100 nM-10 MUM) decreased
colonic contractility by ~60%; this effect was abolished by TRPV1 antagonist 5'
IRTX, but not by CB1 antagonist, SR141716. AA-5-HT (1 MUM-10 MUM) inhibited EJP
by ~30% and IJPs by ~50%. The effects of AA-5-HT on junction potentials were
reversed by SR141716 and 5'-IRTX. AA-5-HT (20 mg/kg; i.p.) inhibited colonic
propulsion by ~30%; SR141716 but not 5'-IRTX reversed this effect. AA-5-HT
decreased VMR by ~50%-60%; these effects were not blocked by SR141716 or 5'-IRTX.
AA-5-HT increased AEA in the colon. CONCLUSIONS AND INFERENCES: The effects of AA
5-HT on visceral sensation and colonic motility are differentially mediated by
CB1, TRPV1 and non-CB1/TRPV1 mechanisms, possibly reflecting the distinct
neuromodulatory roles of endocannabinoid and endovanilloid FAAH substrates in the
mouse intestine.
PMID- 28695709
TI - [Fe-S] cluster assembly in the apicoplast and its indispensability in mosquito
stages of the malaria parasite.
AB - The relict plastid (apicoplast) of the malaria parasite is the site for important
biochemical pathways and is essential for parasite survival. The sulfur
mobilization (SUF) pathway of iron-sulfur [Fe-S] cluster assembly in the
apicoplast of Plasmodium spp. is of interest due to its absence in the human host
suggesting the possibility of antimalarial intervention through apicoplast [Fe-S]
biogenesis. We report biochemical characterization of components of the
Plasmodium falciparum apicoplast SUF pathway after the first step of SUF. In
vitro interaction experiments and in vivo cross-linking showed that apicoplast
encoded PfSufB and apicoplast-targeted PfSufC and PfSufD formed a complex. The
PfSufB-C2 -D complex could function as a scaffold to assemble [4Fe-4S] clusters
in vitro and activity of the PfSufC ATPase was enhanced by PfSufD. Two carrier
proteins, the NifU-like protein PfNfu and the A-type carrier PfSufA are
homodimers, the former mediating transfer of [4Fe-4S] from the scaffold to a
model [4Fe-4S] target protein with higher efficiency. Conditional knockout of
SufS, the enzyme catalyzing the first step of SUF, by selective excision in the
mosquito stages of Plasmodium berghei severely impaired development of
sporozoites in oocysts establishing essentiality of the SUF machinery in the
vector. Our results delineate steps of the complete apicoplast SUF pathway and
demonstrate its critical role in the parasite life cycle.
PMID- 28695710
TI - Current and future microbiological strategies to remove As and Cd from drinking
water.
PMID- 28695711
TI - Cuticular Hydrocarbon Profiles Differentiate Tropical Fire Ant Populations
(Solenopsis geminata, Hymenoptera: Formicidae).
AB - The cuticular hydrocarbons (CHCs) from hexane rinses of workers from two Florida
populations (dark and red forms) of the tropical fire ant, Solenopsis geminata,
were separated by silica gel chromatography and identified by GC/MS analysis.
Both the dark form and the red form produce similar CHCs with carbon chain
lengths ranging from 17 to 35. However, the relative percentages of these CHCs
were consistently different between the two color forms. The largest CHC
component in the dark form is tricosane, and (Z)-9-tricosene for the red form.
There were several significant differences in percent composition. For example,
the dark form was characterized by a low tricosene:tricosane ratio (ca. 0.25),
whereas this ratio was > 2.5 for the red form. The ratio of tricosene:tricosane
can be used as a diagnostic biomarker to delimit the dark and red forms. Cluster
analysis showed that the CHCs patterns of dark form colonies are completely
separated from the CHC pattern of red form colonies. Differences in social
behaviors like nestmate recognition and polygyny between workers from this dark
form and the red form await further investigation.
PMID- 28695712
TI - Transparency and full disclosures: Keys to ethical publishing.
PMID- 28695713
TI - AANP News.
PMID- 28695714
TI - Evaluation of specialist referrals at a rural health care clinic.
AB - PURPOSE: Transition to a value-based care system involves reducing costs
improving population health and enhancing the patient experience. Many rural
hospitals must rely on specialist referrals because of a lack of an internal
system of specialists on staff. This evaluation of the existing specialist
referrals from primary care was conducted to better understand and improve the
referral process and address costs, population health, and the patient
experience. DATA SOURCES: A 6-month retrospective chart review was conducted to
evaluate quality and outcomes of specialty referrals submitted by 10 primary care
providers. During a 6-month period in 2015, there was a total of 13,601 primary
care patient visits and 3814 referrals, a referral rate of approximately 27%.
CONCLUSIONS: The most striking result of this review was that nearly 50% of
referred patients were not making the prescribed specialist appointment. Rather
than finding a large number of unnecessary referrals, we found overall referral
rates higher than expected, and a large percentage of our patients were not
completing their referrals. IMPLICATIONS FOR PRACTICE: The data and patterns
emerging from this investigation would guide the development of referral
protocols for a newly formed accountable care organization and lead to further
quality improvement projects: a LEAN effort, dissemination of results to clinical
and executive staff, protocols for orthopedic and neurosurgical referrals, and
recommendations for future process improvements.
PMID- 28695715
TI - Patient-reported signs of dampness at home may be a risk factor for chronic
rhinosinusitis: A cross-sectional study.
AB - BACKGROUND: An association between dampness at home and respiratory conditions
has been convincingly demonstrated in children. Fewer studies have been performed
in adults, and data are lacking for chronic rhinosinusitis (CRS). With a
prevalence of 10.9% in Europe, CRS imposes a significant burden on quality of
life, as well as economy. OBJECTIVE: Our aim was to study CRS and other
respiratory conditions in relation to dampness at home in a representative sample
of adults. METHODS: The Swedish GA2 LEN questionnaire was answered by 26 577
adults (16-75 years) and included questions on respiratory symptoms, smoking,
education and environmental exposure. CRS was defined according to the EP3 OS
criteria. Dampness was defined as reporting water damage, floor dampness or
visible moulds in the home during the last 12 months. The dampness score was
ranked from 0 to 3, counting the number of signs of dampness reported. RESULTS:
Dampness at home was reported by 11.3% and was independently related to
respiratory conditions after adjustment for demographic and socio-economic
factors and smoking: CRS odds ratio (OR) 1.71; allergic rhinitis OR 1.24; current
asthma OR 1.21; wheeze OR 1.37; nocturnal dyspnoea OR 1.80; nocturnal coughing OR
1.34; and chronic bronchitis OR 1.64. The risk of CRS and most of the other
respiratory conditions was further elevated in subjects reporting multiple signs
of dampness. CONCLUSIONS AND CLINICAL RELEVANCE: This study demonstrated an
independent association between dampness at home and CRS in adults. The high
burden of this and the other respiratory conditions studied is a strong argument
in favour of countering indoor dampness by improving building standards.
PMID- 28695716
TI - Alterations of oncogenes expression in NK cells in patients with cancer.
AB - INTRODUCTION: C-kit/SCF signaling plays a key role in regulating NK cell
homeostasis, maturation, proliferation, and cytotoxicity. C-kit-deficiency in NK
cells results in significant reduction of their number, suggesting an imperative
role for c-kit signaling in NK cell biology. We have recently showed that human
NK cells express not only c-kit-receptor, but also both membrane-bound and
soluble forms of c-kit ligand-Stem cell factor. The goal of this study was to
characterize the c-kit/SCF autocrine loop in peripheral blood NK cells obtained
from patients with cancer. METHODS: Using Smart Flare and qRT-PCR, we have
characterized expression of c-kit and two forms of SCF in patients' NK cells and
correlated these results with the expression of c-myc and STAT3. RESULTS: Our
results demonstrated that the expression of proto-oncogenes c-myc and c-kit was
significantly decreased in NK cells from all cancer patients. Expression of
membrane-bound SCF in NK cells correlated with the presence of remote metastases.
CONCLUSIONS: We suggest that the abnormal signaling and expression of c-kit/SCF,
c-myc, and STAT3 in NK cells is responsible for the defect in their cytolytic
activity in cancer and these defects at the gene expression level may be the
cause rather than the result of tumor progression.
PMID- 28695717
TI - Validation of the short version of Korean functional Health Literacy Test.
AB - AIM: The aim of this study is to validate a short version of the Korean
functional Health Literacy Test. BACKGROUND: Development of a brief and valid
health literacy assessment tool, with an optimal cut-off value, is essential to
identify individuals with low health literacy in the Korean-speaking population.
DESIGN: This is a psychometric validation study of the instrument. METHODS: Item
response analysis using 2-parameter logistic estimates was used for item
reduction. The short form of the Korean functional Health Literacy Test was
validated among 170 nursing students and 129 older adults in Korea. Data were
collected from December 2015 to February 2016. Receiver operating characteristic
curves were constructed to classify health literacy level with the cut-off value.
RESULTS: Item difficulty parameters of the short form of the Korean functional
Health Literacy Test ranged from -1.33 to -0.35; item discrimination ranged from
1.91 to 4.47. Significant differences of the test score were shown between
nursing students and older adults. The cut-off value of 6 out of 8 on the short
form of the Korean functional Health Literacy Test showed a sensitivity of 0.79
and specificity of 0.65. CONCLUSION: The short form of the Korean functional
Health Literacy Test is a valid tool with sufficient diagnostic accuracy to
assess health literacy in the Korean-speaking population.
PMID- 28695718
TI - How does the "new" definition of Oral health and the recent World Oral Health
survey impact dental hygienists?
PMID- 28695719
TI - Corrigendum.
PMID- 28695720
TI - Work assignments, delegation of tasks and job satisfaction among Danish dental
hygienists.
AB - INTRODUCTION: Recent legislation in Denmark has made it possible for dentists to
delegate their tasks to dental hygienists. Previous studies have shown that
Danish dental hygienists primarily were performing assignments within their own
work field. These assignments include prophylaxis or instructing patients in oral
health care. However, studies have also shown that Danish dental hygienists
performed dental nurse assignments such as chair-side assistance, unit cleaning
and disinfection of instruments. OBJECTIVES: The objectives of this study were to
investigate (i) the range of work assignments performed by Danish dental
hygienists, (ii) the types of dentist tasks performed by Danish dental hygienists
and (iii) job satisfaction among Danish dental hygienists. DESIGN: Dental
hygienists graduating in 2004-2007 were invited to participate in this study.
METHODS: Participants answered an email-distributed questionnaire. The
questionnaire consisted of questions regarding job satisfaction, assignments
performed, postgraduate course attendance, receiving assistance from a dental
nurse and which work assignments Danish dental hygienists wish to perform in the
future. RESULTS: The results of this study showed that 90% of Danish dental
hygienists were satisfied with their job and 52% were performing dentists' tasks.
Among dentists' tasks performed by Danish dental hygienists, invasive caries
therapy was the most frequently performed task. CONCLUSION: The type of
assignments performed by Danish dental hygienists today appears to be changing
compared to previous studies. From initially performing prophylaxis and chair
side assistance for the dentist, Danish dental hygienists today are performing a
wider range of tasks which includes dentists' tasks.
PMID- 28695721
TI - Aortic isthmus shunt dynamics in normal and complicated monochorionic
pregnancies.
AB - OBJECTIVE: To study fetal aortic isthmus (AoI) shunt dynamics in monochorionic
(MC) twins. METHODS: Normal and complicated MC pregnancies were prospectively
enrolled. The relationship of isthmus flow index (IFI) with Doppler parameters of
umbilical artery (UA), descending aorta, middle cerebral artery, and ductus
venosus and with left and right ventricular cardiac output and stroke volume was
studied. RESULTS: The IFI was obtained in 180 examinations from 48 pregnancies
(24 twin-twin transfusion syndrome, TTTS; 4 selective intrauterine growth
restriction, sIUGR; 12 TTTS + sIUGR; and 8 uncomplicated). Median gestational age
was 20.9 weeks. AoI diastolic flow was reversed in three cases. UA pulsatility
index (PI) and ductus venosus-PI z-scores were negatively correlated with the IFI
(rs -0.40 and -0.26, respectively, p < 0.001). Regression analysis identified
only UA-PI as a determinant of the IFI (p < 0.001). The IFI was significantly
correlated with left ventricular cardiac output and stroke volume. It did not
differ between TTTS donors and recipients. sIUGR fetuses had significantly lower
IFI compared with normal-grown counterparts (p < 0.001). CONCLUSION: In MC
gestations, AoI shunting is predominantly determined by placental flow
resistance, while cerebral impedance and volume status have no impact. In MC
twins, the relationship between AoI flow and outcome deserves further study in
the setting of sIUGR. (c) 2017 John Wiley & Sons, Ltd.
PMID- 28695722
TI - A systematic review of reviews: exploring the relationship between obesity,
weight loss and health-related quality of life.
AB - This is the first systematic review of reviews to assess the effect of obesity
and weight loss on health-related quality of life (HRQoL). We identified 12 meta
analyses/systematic reviews published between January 2001 and July 2016. They
addressed the following themes: (i) the relationship between weight/body mass
index and HRQoL (baseline/pre-intervention; n = 2). (ii) HRQoL after weight loss
(varied interventions and/or study design; n = 2). (iii) HRQoL after weight loss
(randomized controlled trials only; n = 2). (iv) HRQoL after bariatric surgery (n
= 6). We found that in all populations, obesity was associated with significantly
lower generic and obesity-specific HRQoL. The relationship between weight loss
and improved HRQoL was consistently demonstrated after bariatric surgery, perhaps
due to a greater than average weight loss compared with other treatments.
Improved HRQoL was evident after non-surgical weight loss, but was not
consistently demonstrated, even in randomized controlled trials. This
inconsistency may be attributed to variation in quality of reporting, assessment
measures, study populations and weight-loss interventions. We recommend longer
term studies, using both generic and obesity-specific measures, which go beyond
HRQoL in isolation to exploring mediators of HRQoL changes and interactions with
other variables, such as comorbidities, fitness level and body image.
PMID- 28695723
TI - Burnout syndrome in nurses working in palliative care units: An analysis of
associated factors.
AB - AIMS: To analyse the association between psychological, labour and demographic
factors and burnout in palliative care nursing. BACKGROUND: There is a lack of
published research evaluating burnout in palliative care nursing. METHODS: This
observational cross-sectional study involved 185 palliative care nurses in
Mexico. The primary variables were burnout defined by its three dimensions
(emotional exhaustion, depersonalization and personal accomplishment). As
secondary variables, psychological, labour and demographic factors were
considered. A binary logistic regression model was constructed to determine
factors associated with burnout. RESULTS: A total of 69 nurses experienced high
emotional exhaustion (37.3%), 65 had high depersonalization (35.1%) and 70 had
low personal performance (37.8%). A higher proportion of burnout was found in the
participants who were single parents, working >8 hr per day, with a medium/high
workload, a lack of a high professional quality of life and a self-care deficit.
CONCLUSION: Our multivariate models were very accurate in explaining burnout in
palliative care nurses. These models must be externally validated to predict
burnout and prevent future complications of the syndrome accurately. IMPLICATIONS
FOR NURSING MANAGEMENT: Nurses who present the factors found should be the focus
of interventions to reduce work stress.
PMID- 28695725
TI - Highly Selective and Sensitive Two-Photon Fluorescence Probe for Endogenous
Peroxynitrite Detection and Its Applications in Living Cells and Tissues.
AB - A new two-photon fluorescence probe for endogenous peroxynitrite (ONOO-)
detection was designed and synthesized. The probe exhibits good selectivity and
sensitivity for ONOO- in phosphate-buffered saline solution with a low detection
limit (3.5 * 10-8 M). Furthermore, the probe displays good performance in
detecting endogenous ONOO-, not only in RAW 264.7 cells but also in rat
hippocampal tissue, with a high two-photon cross-section value (delta ~ 100 GM)
at a deep depth of 120 MUm.
PMID- 28695724
TI - Contribution of medications and risk factors to QTc interval lengthening in the
atherosclerosis risk in communities (ARIC) study.
AB - RATIONALE, AIMS, AND OBJECTIVES: Prolongation of the corrected QT (QTc) interval
is associated with increased morbidity and mortality. The association between QTc
interval-prolonging medications (QTPMs) and risk factors with magnitude of QTc
interval lengthening is unknown. We examined the contribution of risk factors
alone and in combination with QTPMs to QTc interval lengthening. METHOD: The
Atherosclerosis Risk in Communities study assessed 15 792 participants with a
resting, standard 12-lead electrocardiogram and >=1 measure of QTc interval over
4 examinations at 3-year intervals (1987-1998). From 54 638 person-visits, we
excluded participants with QRS >= 120 milliseconds (n = 2333 person-visits). We
corrected the QT interval using the Bazett and Framingham formulas. We examined
QTc lengthening using linear regression for 36 602 person-visit observations for
14 160 cohort members controlling for age >= 65 years, female sex, left
ventricular hypertrophy, QTc > 500 milliseconds at the prior visit, and
CredibleMeds categorized QTPMs (Known, Possible, or Conditional risk). We
corrected standard errors for repeat observations per person. RESULTS: Eighty
percent of person-visits had at least one risk factor for QTc lengthening. Use of
QTPMs increased over the 4 visits from 8% to 17%. Among persons not using QTPMs,
history of prolonged QTc interval and female sex were associated with the
greatest QTc lengthening, 39 and 12 milliseconds, respectively. In the absence of
risk factors, Known QTPMs and >=2 QTPMs were associated with modest but greater
QTc lengthening than Possible or Conditional QTPMs. In the presence of risk
factors, >=2 QTPM further increased QTc lengthening. In combination with risk
factors, the association of all QTPM categories with QTc lengthening was greater
than QTPMs alone. CONCLUSION: Risk factors, particularly female sex and history
of prolonged QTc interval, have stronger associations with QTc interval
lengthening than any QTPM category alone. All QTPM categories augmented QTc
interval lengthening associated with risk factors.
PMID- 28695726
TI - Water-Soluble 2D Transition Metal Dichalcogenides as the Hole-Transport Layer for
Highly Efficient and Stable p-i-n Perovskite Solar Cells.
AB - As a hole-transport layer (HTL) material, poly(3,4
ethylenedioxythiophene):polystyrene-sulfonate (PEDOT:PSS) was often criticized
for its intrinsic acidity and hygroscopic effect that would in the long run
affect the stability of perovskite solar cells (Pero-SCs). As alternatives,
herein water-soluble two-dimensional (2D) transition metal dichalcogenides
(TMDs), such as MoS2 and WS2 were used as HTLs in p-i-n Pero-SCs. It was found
that the content of 1T phase in 2D TMDs HTLs is centrally important to the power
conversion efficiencies (PCEs) of Pero-SCs, and the 1T-rich TMDs (as achieved
from exfoliation and without postheating) lead to much higher PCEs. More
importantly, as PEDOT:PSS was replaced by 2D TMDs, both the PCEs and stability of
Pero-SCs were significantly improved. The highest PCEs of 14.35 and 15.00% were
obtained for the Pero-SCs with MoS2 and WS2, respectively, whereas the Pero-SCs
with PEDOT:PSS showed a highest PCE of only 12.44%. These are up to date the
highest PCEs using 2D TMDs as HTLs. After being stored in a glovebox for 56 days,
PCEs of the Pero-SCs using MoS2 and WS2 HTLs remained 78 and 72%, respectively,
whereas the PCEs of Pero-SCs with PEDOT:PSS almost dropped to 0 over 35 days.
This study demonstrates that water-soluble 2D TMDs have great potential for
application as new generation of HTLs aiming at high performance and long-term
stable Pero-SCs.
PMID- 28695727
TI - Ultrawide Spectral Response of CIGS Solar Cells Integrated with Luminescent Down
Shifting Quantum Dots.
AB - Conventional Cu(In1-x,Gax)Se2 (CIGS) solar cells exhibit poor spectral response
due to parasitic light absorption in the window and buffer layers at the short
wavelength range between 300 and 520 nm. In this study, the CdSe/CdZnS core/shell
quantum dots (QDs) acting as a luminescent down-shifting (LDS) layer were
inserted between the MgF2 antireflection coating and the window layer of the CIGS
solar cell to improve light harvesting in the short wavelength range. The LDS
layer absorbs photons in the short wavelength range and re-emits photons in the
609 nm range, which are transmitted through the window and buffer layer and
absorbed in the CIGS layer. The average external quantum efficiency in the
parasitic light absorption region (300-520 nm) was enhanced by 51%. The resulting
short circuit current density of 34.04 mA/cm2 and power conversion efficiency of
14.29% of the CIGS solar cell with the CdSe/CdZnS QDs were improved by 4.35 and
3.85%, respectively, compared with those of the conventional solar cells without
QDs.
PMID- 28695728
TI - Heterogeneous Nanostructure Based on 1T-Phase MoS2 for Enhanced Electrocatalytic
Hydrogen Evolution.
AB - As an electrocatalyst, conventional 2H-phase MoS2 suffers from limited active
sites and inherently low electroconductivity. Phase transitions from 2H to 1T
have been proposed as an effective strategy for optimization of the catalytic
activity. However, complicated chemical exfoliation is generally involved. Here,
MoS2 heterogeneous-phase nanosheets with a 1T phase (1T/2H-MoS2) generated in
situ were prepared through a facile hydrothermal method. The locally introduced
1T-phase MoS2 can not only contribute more active sites but also markedly promote
the electronic conductivity. Because of this unique structure, the as-synthesized
1T/2H-MoS2 nanosheets exhibit remarkable performance for the hydrogen evolution
reaction with a small overpotential of 220 mV at 10 mA/cm2, a small Tafel slope
of 61 mV/decade, and robust stability. This work facilitates the development of a
two-dimensional heterogeneous nanostructure with enhanced applications.
PMID- 28695729
TI - Semi-integrative Voltammetry as an Efficient Tool To Study Simple Electrochemical
Systems in Deep Eutectic Solvents.
AB - The utilization of deep eutectic solvents (DESs) in electrochemical studies has
grown in recent years due to their low cost and environmental friendliness
compared to traditional ionic liquids. However, the determination of diffusion
coefficient (D) and heterogeneous constant rate (k0) using the traditional
electrochemical approach may mask some concerns because of the high viscosity and
limited conductivity in these media. In this work, it is shown that the
determinations of D and k0 in glyceline DES by voltammetric studies using the
Nicholson approach is problematic. Furthermore, the semi-integrative approach is
evaluated which reveals that it is an efficient tool to determine such parameters
that have a significant influence of the electrolyte viscosity and conductivity.
The D values are 2.8 * 10-8 and 4.2 * 10-8 cm2 s-1 for Nicholson and semi
integrative approaches, respectively, using 0.05 M FeCl3 in glyceline at 30
degrees C, which indicates an underestimation of D by employing the Nicholson
equations. Also, k0 is obtained using Saveant's methodology which cannot be
obtained by the typical evaluation of DeltaEp (Nicholson's approach) when DeltaEp
> 200 mV as it occurs in the case of concentrations >= 0.25 M FeCl3, depending on
the potential scan rate.
PMID- 28695730
TI - Hypervalent Iodine/HF Reagents for the Synthesis of 3-Fluoropyrrolidines.
AB - The intramolecular aminofluorination of homoallylamine derivatives using a
reagent system of PhI(OAc)2 and Py.HF in CH2Cl2 at room temperature for 5 h gave
N-tosyl-3-fluoropyrrolidines in good to high yields. Furthermore, the catalytic
aminofluorination was furnished by the reaction using p-iodotoluene as a catalyst
in the presence of Py.HF as a fluorine source and mCPBA as a terminal oxidant.
PMID- 28695731
TI - Investigating the Interaction of Octapeptin A3 with Model Bacterial Membranes.
AB - Octapeptins are cyclic lipopeptides with a broader spectrum of activity against
fungi and polymyxin-resistant Gram-negative and Gram-positive bacteria. In the
present study, we investigated the interaction of octapeptin A3 with asymmetric
outer membrane models of Gram-negative pathogen Pseudomonas aeruginosa using
neutron reflectometry, together with fluorimetric and calorimetry methods. For
the first time, our neutron reflectometry results reveal that the interaction of
octapeptin A3 with the Gram-negative outer membrane involves an initial transient
polar interaction with the phospholipid and lipid A headgroups, followed by the
penetration of the entire octapeptin molecule into the fatty acyl core of the
outer membrane. This mechanism contrasts with that of polymyxin B, which
specifically targets lipid A, whereas octapeptins appear to target both lipid A
and phospholipids. Furthermore, the mechanism of octapeptins does not appear to
be highly dependent on an initial complementary electrostatic interaction with
lipid A, which accounts for their ability to bind to lipid A of polymyxin
resistant Gram-negative bacteria that is modified with cationic moieties that act
to electrostatically repel the cationic polymyxin molecule. The presented
findings shed new light on the mechanism whereby octapeptins penetrate the outer
membrane of polymyxin-resistant Gram-negative pathogens and highlight their
potential as candidates for development as new antibiotics against problematic
multi-drug-resistant pathogens.
PMID- 28695732
TI - Reduction and Simultaneous Removal of 99Tc and Cr by Fe(OH)2(s) Mineral
Transformation.
AB - Technetium (Tc) remains a priority remediation concern due to persistent
challenges, including mobilization due to rapid reoxidation of immobilized Tc,
and competing comingled contaminants, e.g., Cr(VI), that inhibit Tc(VII)
reduction and incorporation into stable mineral phases. Here Fe(OH)2(s) is
investigated as a comprehensive solution for overcoming these challenges, by
serving as both the reductant, (Fe(II)), and the immobilization agent to form Tc
incorporated magnetite (Fe3O4). Trace metal analysis suggests removal of Tc(VII)
and Cr(VI) from solution occurs simultaneously; however, complete removal and
reduction of Cr(VI) is achieved earlier than the removal/reduction of comingled
Tc(VII). Bulk oxidation state analysis of the final magnetite solid phase by
XANES shows that the majority of Tc is Tc(IV), which is corroborated by XPS
measurements. Furthermore, EXAFS results show successful, albeit partial, Tc(IV)
incorporation into magnetite octahedral sites. Cr XPS analysis indicates
reduction to Cr(III) and the formation of a Cr-incorporated spinel, Cr2O3, and
Cr(OH)3 phases. Spinel (modeled as Fe3O4), goethite (alpha-FeOOH), and feroxyhyte
(delta-FeOOH) are detected in all reacted final solid phase samples analyzed by
XRD. Incorporation of Tc(IV) has little effect on the spinel lattice structure.
Reaction of Fe(OH)2(s) in the presence of Cr(III) results in the formation of a
spinel phase that is a solid solution between magnetite (Fe3O4) and chromite
(FeCr2O4).
PMID- 28695733
TI - Efficient All-Solution Processed Quantum Dot Light Emitting Diodes Based on
Inkjet Printing Technique.
AB - Quantum dot light emitting diodes (QLEDs) are increasingly attractive owing to
their compatibility with the inkjet printing process and potential application in
low-cost large-area full-color pixelated display. The strategy for controlling
the morphology of the quantum dot layer is definitely critical for realizing all
solution processed QLEDs with high performance, which certainly requires in-depth
thinking regarding the design of ink composition and their optimization in the
printing process. Herein, by carefully controlling the quantum dot ink
composition and physicochemical properties, we demonstrate that the viscosity,
contact angle, and the three-phase contact line moving would affect the final
morphology of the quantum dot film formed by inkjet printing. We achieved coffee
ring-free and low-roughness quantum dot film, and all-solution processed QLEDs
with normal structure were fabricated for the first time. The devices have a low
turn-on voltage of 2.0 V, a luminance of 12100 cd/m2 at the voltage of 12 V, and
a maximum current efficiency of 4.44 cd/A at the luminance of 1974 cd/m2, which
is the best result to date for inkjet-printed red QLEDs. The results will pave
the way for future application of inkjet printing in solution processed pixelated
QLED display.
PMID- 28695734
TI - One-Pot Synthesis and Purification of Ultralong Silver Nanowires for Flexible
Transparent Conductive Electrodes.
AB - Metal nanowires (NWs) have become the most promising candidates for the next
generation of flexible transparent conductive electrodes (FTCEs), with high
transmittance and low sheet resistance. In this work, ultralong silver NWs (Ag
NWs), ~220 MUm (even larger than 400 MUm) in length and ~55 nm in diameter
(aspect ratio: ~4000), were synthesized via a one-pot polyol process using high
molecular weight poly(vinylpyrrolidone) (Mw = 1 300 000) and an appropriate
concentration of FeCl3 (12.5 MUM) through hydrothermal reaction. The prepared Ag
NWs were purified by a filter cloth (pore size: about 30 * 50 MUm2) to remove the
Ag nanoparticles and short-length Ag NWs. The FTCE based on the ultralong Ag NWs
without any post-treatments exhibits low sheet resistance of 155.0 Omega sq-1 and
transmittance of 97.70% at 550 nm. The outstanding performance of FTECs
demonstrated that the ultralong Ag NWs are ideal materials for applications in
flexible transparent optical devices.
PMID- 28695735
TI - Investigation and Demonstration of Catalyst/Initiator-Driven Selectivity in Thiol
Michael Reactions.
AB - Thiol-Michael "click" reactions are essential synthetic tools in the preparation
of various materials including polymers, dendrimers, and other macromolecules.
Despite increasing efforts to apply thiol-Michael chemistry in a controlled
fashion, the selectivity of base- or nucleophile-promoted thiol-Michael reactions
in complex mixtures of multiple thiols and/or acceptors remains largely unknown.
Herein, we report a thorough fundamental study of the selectivity of thiol
Michael reactions through a series of 270 ternary reactions using 1H NMR
spectroscopy to quantify product selectivity. The varying influences of different
catalysts/initiators are explored using ternary reactions between two Michael
acceptors and a single thiol or between a single Michael acceptor and two thiols
using three different catalysts/initiators (triethylamine, DBU, and
dimethylphenylphosphine) in chloroform. The results from the ternary reactions
provide a platform from which sequential quaternary, one-pot quaternary, and
sequential senary thiol-Michael reactions were designed and their selectivities
quantified. These results provide insights into the design of selective thiol
Michael reactions that can be used for the synthesis and functionalization of
multicomponent polymers and further informs how catalyst/initiator choice
influences the reactivity between a given thiol and Michael acceptor.
PMID- 28695736
TI - Flow Synthesis of Diaryliodonium Triflates.
AB - A safe and scalable synthesis of diaryliodonium triflates was achieved using a
practical continuous-flow design. A wide array of electron-rich to electron
deficient arenes could readily be transformed to their respective diaryliodonium
salts on a gram scale, with residence times varying from 2 to 60 s (44 examples).
PMID- 28695737
TI - Interplay of Conformational and Chemical Transformations of Ortho-Substituted
Aromatic Nitroso Oxides: Experimental and Theoretical Study.
AB - The mechanism of the photooxidation of aromatic azides containing a substituent
at one of the ortho positions (2,4-dimethoxyphenyl azide (1a) and 2-methyl-4
[(2E)-1-methylbut-2-en-1-yl]phenyl azide (1b)) was studied in acetonitrile. The
electronic spectra and the kinetic regularities of the consumption of
corresponding nitroso oxides, which are the reaction intermediates, were
investigated by flash photolysis. Owing to the one-and-a-half order of the C-N
and N-O bonds and asymmetric molecule structure these nitroso oxides exist as
four conformers (cis/syn, cis/anti, trans/syn, and trans/anti). The conformers
differ in the spectral properties and in the reactivity in various irreversible
transformations. The only product, (2Z,4E)-4-methoxy-6-oxohepta-2,4-dienenitrile
oxide (7a), was observed during photooxidation of 1a, whereas transformations of
the nitroso oxide isomers derived from 1b led to a set of stable products: the
cis/anti isomer was transformed into (3,4,7-trimethyl-3a,4-dihydro-2,1
benzisoxazol-5(3H)-ylidene)ethanal (10), the trans isomers recombined forming the
corresponding nitro and nitroso compounds, and the most reactive cis/syn isomer
was transformed into ortho-nitrosobenzyl alcohol 11. The last was oxidized slowly
to the corresponding benzaldehyde 12. Interaction of 11 and 12 led to the
formation of (Z)-1,2-bis(2-formyl-4-((2E)-1-methylbut-2-en-1-yl)phenyl)diazene-1
oxide (13). The DFT simulation and kinetic modeling of the nitroso oxide
transformations as well as the product analysis allowed revealing the fine
details of the mechanism of decay for these species.
PMID- 28695738
TI - Proton Shuttling and Reaction Paths in Dissociative Electron Attachment to o- and
p-Tetrafluorohydroquinone, an Experimental and Theoretical Study.
AB - Here we present a combined experimental and theoretical study on the
fragmentation of o- and p-tetrafluorohydroquinone upon low energy electron
attachment. Despite an identical ring-skeleton and identical functional groups in
these constitutional isomers, they show distinctly different fragmentation
patterns, a phenomenon that cannot be explained by distinct resonances or
different thermochemistry. Using high-level quantum chemical calculations with
the computationally affordable domain localized pair natural orbital approach,
DLPNO-CCSD(T), we are able to provide a complete and accurate description of the
respective reaction dynamics, revealing proton shuttling and transition states
for competing channels as the explanation for the different behavior of these
isomers. The results represent a "schoolbook example" of how the combination of
experiment and modern high-level theory may today provide a thorough
understanding of complex reaction dynamics by computationally affordable means.
PMID- 28695739
TI - Depth Stratification Leads to Distinct Zones of Manganese and Arsenic
Contaminated Groundwater.
AB - Providing access to safe drinking water is a global challenge, for which
groundwater is increasingly being used throughout the world. However, geogenic
contaminants limit the suitability of groundwater for domestic purposes over
large geographic areas across most continents. Geogenic contaminants in
groundwater are often evaluated individually, but here we demonstrate the need to
evaluate multiple contaminants to ensure that groundwater is safe for human
consumption and agricultural usage. We compiled groundwater chemical data from
three aquifer regions across the world that have been reported to have widespread
As and Mn contamination including the Glacial Aquifer in the U.S., the Ganges
Brahmaputra-Mehta Basin within Bangladesh, and the Mekong Delta in Cambodia,
along with newly sampled wells in the Yangtze River Basin of China. The
proportion of contaminated wells increase by up to 40% in some cases when both As
and Mn contaminants are considered. Wilcoxon rank-sum analysis indicates that Mn
contamination consistently occurs at significantly shallower depths than As
contaminated wells in all regions. Arsenic concentrations in groundwater are well
predicted by redox indicators (Eh and dissolved oxygen) whereas Mn shows no
significant relationship with either parameter. These findings illustrate that
the number of safe wells may be drastically overestimated in some regions when Mn
contamination is not taken into account and that depth may be used as a
distinguishing variable in efforts to predict the presence of groundwater
contaminants regionally.
PMID- 28695740
TI - Electronic Structure and Band Alignment at the NiO and SrTiO3 p-n
Heterojunctions.
AB - Understanding the energetics at the interface, including the alignment of valence
and conduction bands, built-in potentials, and ionic and electronic
reconstructions, is an important challenge in designing oxide interfaces that
have controllable multifunctionalities for novel (opto-)electronic devices. In
this work, we report detailed investigations on the heterointerface of wide-band
gap p-type NiO and n-type SrTiO3 (STO). We show that despite a large lattice
mismatch (~7%) and dissimilar crystal structure, high-quality NiO and Li-doped
NiO (LNO) thin films can be epitaxially grown on STO(001) substrates through a
domain-matching epitaxy mechanism. X-ray photoelectron spectroscopy studies
indicate that NiO/STO heterojunctions form a type II "staggered" band alignment.
In addition, a large built-in potential of up to 0.97 eV was observed at the
interface of LNO and Nb-doped STO (NbSTO). The LNO/NbSTO p-n heterojunctions
exhibit not only a large rectification ratio of 2 * 103 but also a large ideality
factor of 4.3. The NiO/STO p-n heterojunctions have important implications for
applications in photocatalysis and photodetectors as the interface provides
favorable energetics for facile separation and transport of photogenerated
electrons and holes.
PMID- 28695741
TI - Effect of Ionic Strength and Surface Charge Density on the Kinetics of Cellulose
Nanocrystal Thin Film Swelling.
AB - This work explores cellulose nanocrystal (CNC) thin films (<50 nm) and particle
particle interactions by investigating film swelling in aqueous solutions with
varying ionic strength (1-100 mM). CNC film hydration was monitored in situ via
surface plasmon resonance, and the kinetics of liquid uptake were quantified. The
contribution of electrostatic double-layer forces to film swelling was elucidated
by using CNCs with different surface charges (anionic sulfate half ester groups,
high and low surface charge density, and cationic trimethylammonium groups).
Total water uptake in the thin films was found to be independent of ionic
strength and surface chemistry, suggesting that in the aggregated state van der
Waals forces dominate over double-layer forces to hold the films together.
However, the rate of swelling varied significantly. The water uptake followed
Fickian behavior, and the measured diffusion constants decreased with the ionic
strength gradient between the film and the solution. This work highlights that
nanoparticle interactions and dispersion are highly dependent on the state of
particle aggregation and that the rate of water uptake in aggregates and thin
films can be tailored based on surface chemistry and solution ionic strength.
PMID- 28695742
TI - Human Regulatory Protein Ki-1/57 Is a Target of SUMOylation and Affects PML
Nuclear Body Formation.
AB - Ki-1/57 is a nuclear and cytoplasmic regulatory protein first identified in
malignant cells from Hodgkin's lymphoma. It is involved in gene expression
regulation on both transcriptional and mRNA metabolism levels. Ki-1/57 belongs to
the family of intrinsically unstructured proteins and undergoes phosphorylation
by PKC and methylation by PRMT1. Previous characterization of its protein
interaction profile by yeast two-hybrid screening showed that Ki-1/57 interacts
with proteins of the SUMOylation machinery, the SUMO E2 conjugating enzyme UBC9
and the SUMO E3 ligase PIAS3, which suggested that Ki-1/57 could be involved with
this process. Here we identified seven potential SUMO target sites (lysine
residues) on Ki-1/57 sequence and observed that Ki-1/57 is modified by SUMO
proteins in vitro and in vivo. We showed that SUMOylation of Ki-1/57 occurred on
lysines 213, 276, and 336. In transfected cells expressing FLAG-Ki-1/57 wild
type, its paralog FLAG-CGI-55 wild-type, or their non-SUMOylated triple mutants,
the number of PML-nuclear bodies (PML-NBs) is reduced compared with the control
cells not expressing the constructs. More interestingly, after treating cells
with arsenic trioxide (As2O3), the number of PML-NBs is no longer reduced when
the non-SUMOylated triple mutant Ki-1/57 is expressed, suggesting that the
SUMOylation of Ki-1/57 has a role in the control of As2O3-induced PML-NB
formation. A proteome-wide analysis of Ki-1/57 partners in the presence of either
SUMO-1 or SUMO-2 suggests that the involvement of Ki-1/57 with the regulation of
gene expression is independent of the presence of either SUMO-1 or SUMO-2;
however, the presence of SUMO-1 strongly influences the interaction of Ki-1/57
with proteins associated with cellular metabolism, maintenance, and cell cycle.
PMID- 28695743
TI - Molecular Theory of Hydration at Different Temperatures.
AB - Solvation plays an important role in diverse chemical processes ranging from
reaction kinetics to molecular recognition, solubility, and phase separations.
Despite a long-history of theoretical exploration, quantitative prediction of
solvation remains a theoretical challenge without relying on the macroscopic
properties of the solvent as an input. Here we present a molecular density
functional theory that provides a self-consistent description of the solvation
structure and thermodynamic properties of small organic molecules in liquid water
at different temperatures. Based on the solute configuration and force-field
parameters generated from first-principles calculations, the theoretical
predictions are found in good agreement with experimental data for the hydration
free energies of 197 organic molecules in a temperature range from 0 to 40
degrees C. In addition to calibration with experimental results, the theoretical
predictions are compared with recent molecular dynamics simulations for the
hydration of five highly explosive nitrotoluenes. This work demonstrates the
potential of the classical density functional theory for high-throughput
prediction of solvation properties over a broad range of temperatures.
PMID- 28695744
TI - Genome editing: the breakthrough technology for inherited retinal disease?
AB - INTRODUCTION: Genetic alterations resulting in a dysfunctional retinal pigment
epithelium and/or degenerating photoreceptors cause impaired vision. These
juxtaposed cells in the retina of the posterior eye are crucial for the visual
cycle or phototransduction. Deficits in these biochemical processes perturb
neural processing of images capturing the external environment. Notably, there is
a distinct lack of clinically approved pharmacological, cell- or gene-based
therapies for inherited retinal disease. Gene editing technologies are rapidly
advancing as a realistic therapeutic option. Areas covered: Recent discovery of
endonuclease-mediated gene editing technologies has culminated in a surge of
investigations into their therapeutic potential. In this review, the authors
discuss gene editing technologies and their applicability in treating inherited
retinal diseases, the limitations of the technology and the research obstacles to
overcome before editing a patient's genome becomes a viable treatment option.
Expert opinion: The ability to strategically edit a patient's genome constitutes
a treatment revolution. However, concerns remain over the safety and efficacy of
either transplanting iPSC-derived retinal cells following ex vivo gene editing,
or with direct gene editing in vivo. Ultimately, further refinements to improve
efficacy and safety profiles are paramount for gene editing to emerge as a widely
available treatment option.
PMID- 28695745
TI - Treating autoimmune disorders with venom-derived peptides.
AB - INTRODUCTION: The effective treatment of autoimmune diseases remains a challenge.
Voltage-gated potassium Kv1.3 channels, which are expressed in lymphocytes, are a
new therapeutic target for treating autoimmune disease. Consequently, Kv1.3
channel-inhibiting venom-derived peptides are a prospective resource for new drug
discovery and clinical application. Area covered: Preclinical and clinical
studies have produced a wealth of information on Kv1.3 channel-inhibiting venom
derived peptides, especially from venomous scorpions and sea anemones. This
review highlights the advances in screening and design of these peptides with
diverse structures and potencies. It focuses on representative strategies for
improving peptide selectivity and discusses the preclinical research on those
venom-derived peptides as well as their clinical developmental status. Expert
opinion: Encouraging results indicate that peptides isolated from the venom of
venomous animals are a large resource for discovering immunomodulators that act
on Kv1.3 channels. Since the structural diversity of venom-derived peptides
determines the variety of their pharmacological activities, the design and
optimization of venom-peptides for improved Kv1.3 channel-specificity has been
advanced through some representative strategies, such as peptide chemical
modification, amino acid residue truncation and binding interface modulation.
These advances should further accelerate research, development and the future
clinical application of venom-derived peptides selectively targeting Kv1.3
channels.
PMID- 28695746
TI - Improvement of hepatogenic differentiation of iPS cells on an aligned
polyethersulfone compared to random nanofibers.
AB - The application of stem cells holds great promises in cell and tissue
transplants. This study was designed to compare the hepatogenic differentiation
of iPSCs on aligned PES/COL versus random. Aligned and random PES/COL nanofibrus
scaffolds were fabricated by electrospining and their surface modified through
plasma treatment and collagen coating. The scaffolds were characterized using
scanning electron microscopy (SEM) and ATR-FTIR. Morphology and biochemical
activities of the differentiated hepatocyte-like cells (HLCs) were examined after
5 and 20 days of differentiation. Real-Time RT-PCR and ICC showed no significant
difference in the mRNA and protein levels of two important definitive endoderm
specific markers, including Sox17 and Foxa2 between two scaffolds. However, Real
Time RT-PCR analysis indicated an increase in the expression of Cyp7A1 gene over
the period of the differentiation procedure on the aligned nanofibers but there
was no difference in other genes such as Albumin and CK19. Moreover, comparison
of hepatogenic differentiation evaluated by Albumin production in conditioned
media of HLCs differentiated on aligned PES/COL, showed increase expression of
these markers after 20 days compared to that of the random nanofibers. Taken
together, the results of this study may indicate that aligned PES/COL nanofibrous
scaffolds can improve terminal differentiation of HLCs from iPSCs.
PMID- 28695747
TI - Novel strategies for anti-aging drug discovery.
AB - INTRODUCTION: Scientific achievements in the last few decades, leading to
effective therapeutic interventions, have dramatically improved human life
expectancy. Consequently, aging has become a significant problem and represents
the major risk factor for most human pathologies including diabetes,
cardiovascular diseases, neurological disorders, and cancer. Scientific
discoveries over the past two decades have been instrumental in dissecting
molecular mechanism(s) which play important roles in determining longevity. The
same understanding has also led to the acknowledgement of the plurality of
'causes' which act either alone or in combination to create the condition which
can be defined as 'aging'. Areas covered: Over the years, several concepts have
been put forward for the development of a viable anti-aging regimen. In this
review, the authors extensively review anti aging interventions based on caloric
restriction, activation of telomerase, autophagy inducers, senolytic
therapeutics, plasma membrane redox system (PMRS) activators, epigenetic
modulators, and stem cell therapies. Expert opinion: Based upon our current
understanding, one of the most promising approaches for a successful anti-aging
strategy includes the activation of adenosine monophosphate dependent protein
kinase (AMPK). Another strategy may involve activation of PMRS. Future research
efforts are likely to focus on nutrient and energy sensing molecular pathways
which include mTOR, IGF-1, AMPK and the sirtuins.
PMID- 28695748
TI - Proteomic profiling of the cancer cell secretome: informing clinical research.
AB - INTRODUCTION: Cancer represents one of the major causes of human deaths.
Identification of proteins as biomarkers for early detection of cancer and
therapeutic targets for cancer treatment are important issues in precision
medicine. Secretome of cancer cells represents the collection of proteins
secreted or shed from cancer cells. Proteomic profiling of the cancer cell
secretome has been proven to be a convenient and efficient way to discover cancer
biomarker and/or therapeutic targets. Areas covered: There have been numerous
reviews describing the history and application of secretome analysis in cancer
biomarker/therapeutic target research. The present review focuses on the
technological advancement for profiling low-molecular-mass proteins in secretome,
the latest information regarding the new candidate biomarkers and molecular
mechanisms discovered on the basis of cancer cell secretome analysis, as well as
the previously discovered candidate biomarkers that enter into clinical trials.
Expert commentary: Current technologies for protein sample preparation/separation
and MS-based protein identification have allowed in-depth analysis of cancer cell
secretome. Future efforts should focus on the comprehensiveness of cancer cell
secretome, meta-analysis of different secretome datasets and integrated analysis
via combining other omics datasets, as well as the incorporation of MS-based
biomarker verification pipeline into both preclinical studies and clinical
trials.
PMID- 28695749
TI - The use of cochlear's SCAN and wireless microphones to improve speech
understanding in noise with the Nucleus6(r) CP900 processor.
AB - OBJECTIVES: The newest Nucleus CI processor, the CP900, has two new options to
improve speech-in-noise perception: (1) use of an adaptive directional microphone
(SCAN mode) and (2) wireless connection to MiniMic1 and MiniMic2 wireless remote
microphones. DESIGN: An analysis was made of the absolute and relative benefits
of these technologies in a real-world mimicking test situation. Speech perception
was tested using an adaptive speech-in-noise test (sentences-in-babble noise). In
session A, SRTs were measured in three conditions: (1) Clinical Map, (2) SCAN and
(3) MiniMic1. Each was assessed for three distances between speakers and CI
recipient: 1 m, 2 m and 3 m. In session B, the benefit of the use of MiniMic2 was
compared to benefit of MiniMic1 at 3 m. STUDY SAMPLE: A group of 13 adult CP900
recipients participated. RESULTS: SCAN and MiniMic1 improved performance compared
to the standard microphone with a median improvement in SRT of 2.7-3.9 dB for
SCAN at 1 m and 3 m, respectively, and 4.7-10.9 dB for the MiniMic1. MiniMic1
improvements were significant. MiniMic2 showed an improvement in SRT of 22.2 dB
compared to 10.0 dB for MiniMic1 (3 m). CONCLUSIONS: Digital wireless
transmission systems (i.e. MiniMic) offer a statistically and clinically
significant improvement in speech perception in challenging, realistic listening
conditions.
PMID- 28695750
TI - "I did not see a need to get tested before, everything was going well with my
health": a qualitative study of HIV-testing decision-making in KwaZulu-Natal,
South Africa.
AB - Few studies have examined HIV-testing decision-making since the South African
national HIV counseling and testing campaign in 2010-2011 and subsequent
expansion in antiretroviral therapy (ART) eligibility in 2012. We describe HIV
testing decision-making and pathways to testing among participants in Pathways to
Care, a cohort study of newly-diagnosed HIV-positive adults in KwaZulu-Natal. Our
analysis is embedded within a theoretical framework informed by Arthur Kleinman's
work on pluralistic healthcare systems, and the concept of diagnostic itineraries
(i.e., the route taken to HIV testing). We conducted 26 semi-structured
interviews in 2012, within one month of participants' diagnosis. Most (n = 22)
deferred testing until they had developed symptoms, and then often sought
recourse in non-biomedical settings. Of the eleven symptomatic participants who
accessed professional medical services prior to testing, only three reported that
a healthcare professional had offered or recommended an HIV test. Although ART
emerged as an important motivator, offering hope of health and normalcy, fear of
death and HIV-related stigma remained key barriers. Despite national policy
changes in testing and treatment, health system and individual factors
contributed to ongoing high levels of late diagnosis of HIV in this study
population. Encouraging local health systems to direct clients toward HIV
testing, and continuing to raise awareness of the benefits of routine testing
remain important strategies to reduce delayed diagnoses.
PMID- 28695751
TI - Watercress-based electrospun nanofibrous scaffolds enhance proliferation and
stemness preservation of human adipose-derived stem cells.
AB - The present study describes the effects of Watercress extract (WE) based
electrospun nanofibrous mats on the regulation of adhesion, proliferation,
cytoprotection and stemness preservation of adipose-derived stem cells (ADSCs).
Watercress (Nasturtium officinale) is one of the most important medicinal plant
with a board spectrum of biological functions. For this purpose, WE-loaded PCL
PEG nanofibers were fabricated by electrospinning and characterized using FE-SEM
and FTIR. Adhesion, proliferation and cytoprotection of ADSCs on the nanofibers
was investigated using FE-SEM and MTT assays. Analysis of cell cycle was carried
out by flow-cytometry. Finally, qPCR was applied to measure the expression levels
of cell cycle-regulated genes and stemness markers of ADSCs grown on the
nanofibers. In this study, we found that WE-loaded PCL-PEG nanofibers had great
antioxidant potential and exhibited higher cytoprotection, better adhesion, and
significantly increased proliferation of ADSCs. The greater proliferation and
preserving stemness ability of ADSCs on WE based nanofibers was further confirmed
by higher expression levels of cell cycle-regulated genes and stemness markers.
These results demonstrate that WE-loaded PCL-PEG electrospun nanofibrous mats
appear suitable to support ADSCs adhesion and proliferation while concurrently
preserving the cell stemness, therefore representing a hopeful approach for
applying in stem cell based regenerative medicine.
PMID- 28695752
TI - Stabilization of protein-protein interactions in drug discovery.
AB - INTRODUCTION: PPIs are involved in every disease and specific modulation of these
PPIs with small molecules would significantly improve our prospects of developing
therapeutic agents. Both industry and academia have engaged in the identification
and use of PPI inhibitors. However in comparison, the opposite strategy of
employing small-molecule stabilizers of PPIs is underrepresented in drug
discovery. Areas covered: PPI stabilization has not been exploited in a
systematic manner. Rather, this concept validated by a number of therapeutically
used natural products like rapamycin and paclitaxel has been shown
retrospectively to be the basis of the activity of synthetic molecules
originating from drug discovery projects among them lenalidomide and tafamidis.
Here, the authors cover the growing number of synthetic small-molecule PPI
stabilizers to advocate for a stronger consideration of this as a drug discovery
approach. Expert opinion: Both the natural products and the growing number of
synthetic molecules show that PPI stabilization is a viable strategy for drug
discovery. There is certainly a significant challenge to adapt compound
libraries, screening techniques and downstream methodologies to identify,
characterize and optimize PPI stabilizers, but the examples of molecules reviewed
here in our opinion justify these efforts.
PMID- 28695753
TI - Psychosocial Screening Among Youth Seeking Weight Management Treatment.
AB - The objectives of this study were to identify rates of, and factors associated
with, "at-risk" scores on a brief psychosocial screener among overweight/obese
youth seeking weight management treatment, as well as concordance between youth
and caregiver reports. A retrospective chart review of 1443 consecutive patients
ages 4 to 18 years and their caregivers was conducted. Almost 1 in 4 youth with
overweight/obesity presented with psychosocial symptoms in the at-risk range for
significant mental health issues based on caregiver report on the Pediatric
Symptom Checklist (PSC) and 1 in 6 based on youth self-report on the Youth
Pediatric Symptom Checklist (Y-PSC). Concordance between caregiver and youth was
fair (agreement 24% to 40%). Higher scores were associated with male sex and
older age on the PSC and with indication of depressive disorder in the electronic
medical record on the Y-PSC. Conducting a brief psychosocial screen in
comprehensive weight management programs is feasible and clinically indicated.
PMID- 28695754
TI - Controlled arterial reflow after ischemia induces better outcomes in the juvenile
rat brain.
AB - Our objective was to determine whether controlled reflow on one side and/or the
other side after bilateral carotid occlusion release could reduce cell death in
focal ischemic P14 rats. Arterial blood flow was measured using ultrasonography.
Cell death, inflammation and nitrotyrosine were measured using
immunofluorescence. When reflow was first induced in the contralateral side, we
observed improved outcome markers compared with those when reflow was first
induced in the ipsilateral side and/or simultaneous reflow was induced in both
sides. Our data suggest that progressive rerouting of arterial flow through the
circle of Willis toward the ischemic site reduced cell death.
PMID- 28695755
TI - Ibrutinib therapy is effective in B-cell prolymphocytic leukemia exhibiting MYC
aberrations.
PMID- 28695756
TI - Double carbapenem therapy (DCT) for bacteremia due to carbapenem-resistant
Klebsiella pneumoniae (CRKP): from test tube to clinical practice.
PMID- 28695758
TI - Differential vergence movements in reading Chinese and English: Greater fixation
initial binocular disparity is advantageous in reading the denser orthography.
AB - We explore two aspects of exovergence: we test whether smaller binocular fixation
disparities accompany the shorter saccades and longer fixations observed in
reading Chinese; we test whether potentially advantageous psychophysical effects
of exovergence (cf. Arnold & Schindel, 2010; Kersten & Murray, 2010) transfer to
text reading. We report differential exovergence in reading Chinese and English:
Chinese readers begin fixations with more binocular disparity, but end fixations
with a disparity closely similar to that of the English readers. We conclude that
greater fixation-initial binocular fixation disparity can be adaptive in the
reading of visually and cognitively denser text.
PMID- 28695757
TI - Association between Snoring and High-Risk Carotid Plaque Features.
AB - Objectives Previous studies have demonstrated an association between snoring and
carotid disease independent of sleep apnea. The aim of this study was to quantify
the association between self-reported snoring and high-risk carotid plaque
features on magnetic resonance imaging (MRI) that predict stroke. Study Design
Cross-sectional. Setting Tertiary care university hospital and affiliated county
hospital. Methods We surveyed 133 subjects with asymptomatic carotid artery
disease that had been previously evaluated with high-resolution MRI. The survey
captured data on self-reported snoring (exposure) and covariates (age, sex, body
mass index, and sleep apnea via the STOP-Bang questionnaire). A subset of
patients underwent home sleep apnea testing. High-risk carotid plaque features
were identified on the high-resolution MRI and included thin/ruptured fibrous cap
and intraplaque hemorrhage (outcomes). We quantified the association between
snoring and high-risk carotid plaque features with the chi-square test
(unadjusted analysis) and multivariate logistic regression adjusting for the
covariates. Results Of 133 subjects surveyed, 61 (46%) responded; 32 (52%)
reported snoring. Significantly higher proportions of snorers than nonsnorers had
a thin/ruptured fibrous cap (56% vs 25%, P = .01) and intraplaque hemorrhage (63%
vs 29%, P < .01). In multivariate analysis, snoring was associated with
thin/ruptured fibrous cap (odds ratio, 4.4; 95% CI, 1.1-16.6; P = .04) and
intraplaque hemorrhage (odds ratio, 8.2; 95% CI, 2.1-31.6; P < .01) after
adjusting for age, sex, body mass index, and sleep apnea. Conclusion This pilot
study suggests a significant independent association between snoring and high
risk carotid plaque features on MRI. Further study is warranted to confirm these
results in a larger cohort of subjects.
PMID- 28695759
TI - Diffusion tensor imaging findings suggestive of white matter alterations in a
canine model of mucopolysaccharidosis type I.
AB - Purpose We investigated fractional anisotropy (FA) and radial diffusivity (RD) in
a canine model of mucopolysaccharidosis (MPS). We hypothesized that canines
affected with MPS would exhibit decreased FA and increased RD values when
compared to unaffected canines, a trend that has been previously described in
humans with white matter diseases. Methods Four unaffected canines and two
canines with MPS were euthanized at 18 weeks of age. Their brains were imaged
using high-resolution diffusion tensor imaging (DTI) on a 7T small-animal
magnetic resonance imaging system. One hundred regions of interest (ROIs) were
placed in each of four white matter regions: anterior and posterior regions of
the internal capsule (AIC and PIC, respectively) and anterior and posterior
regions of the centrum semiovale (ACS and PCS, respectively). For each specimen,
average FA and RD values and associated 95% confidence intervals were calculated
from 100 ROIs for each brain region. Results For each brain region, the FA values
in MPS brains were consistently lower than in unaffected dogs, and the RD values
in MPS dogs were consistently higher, supporting our hypothesis. The confidence
intervals for affected and unaffected canines did not overlap in any brain
region. Conclusion FA and RD values followed the predicted trend in canines
affected with MPS, a trend that has been described in humans with lysosomal
storage and dysmyelinating diseases. These findings suggest that the canine model
parallels MPS in humans, and further indicates that quantitative DTI analysis of
such animals may be suitable for future study of disease progression and
therapeutic response in MPS.
PMID- 28695760
TI - Association between proteomic profile and molecular response in chronic myeloid
leukemia patients.
PMID- 28695761
TI - Tinnitus and Its Effect on the Quality of Life of Sufferers: A Nigerian Cohort
Study.
AB - Objectives To evaluate the quality of life of patients with ongoing tinnitus.
Study Design This was a cross-sectional study of patients with ongoing tinnitus.
Setting The study was carried out in a tertiary hospital in southeastern Nigeria.
Subjects and Methods Subjects are adults who presented to the otorhinolaryngology
clinic with tinnitus as their primary complaint. Pure-tone audiometry, tinnitus
pitch, and loudness matching were done. The Tinnitus Handicap Inventory (THI)
questionnaire was used in assessing their quality of life. Results There were 63
participants within the age range of 16 to 74 years; 20 (31.7%) were male and 43
(68.3%) were female. The mean duration of tinnitus was 26.7 +/- 38.1 months.
Nineteen (30.2%) participants had bilateral tinnitus while 44 (69.8%) had
unilateral tinnitus. The mean THI score was 36.6 +/- 19.7. The most reported
handicap was anxiety and difficulty with concentration followed by depression and
irritability. There was no correlation between the disability shown by the THI
score and the age, sex, duration of the tinnitus, the tinnitus pitch, tinnitus
loudness, or the laterality of the tinnitus. There was a significant positive
correlation between the grade of hearing loss and the level of disability
reported in the THI ( P = .01). Conclusion Tinnitus sufferers appear to have
poorer quality of life compared with nonsufferers. This quality-of-life
affectation is likely to be worse in those with disabling hearing loss but does
not appear to be related to their age, sex, symptom duration, or the loudness and
pitch of their tinnitus.
PMID- 28695762
TI - A review on the performance of osteoporosis self-assessment tool for Asians in
determining osteoporosis and fracture risk.
AB - The prevalence of osteoporosis in Asian countries is growing. An effective
screening method will enable patients at risk for osteoporosis to receive early
diagnosis and treatment, and avoid overcrowding the limited dual-energy x-ray
absorptiometry (DXA) machines available in Asian countries. Many simple
osteoporosis screening algorithms have been developed but they are not validated
for use in Asian populations. osteoporosis self-assessment tools for Asians
(OSTA), established using a multinational Asian cohort, is the first screening
algorithm that caters for the Asian populations. It considers only body weight
and age in the algorithm. It shows consistently high performance and sensitivity
in identifying postmenopausal women at risk for osteoporosis in many Asian
countries. Its usage has been expanded for identifying osteoporosis in men, as
well as determining fracture risk for both sexes. However, the performance of
OSTA is influenced by age, sex, ethnicity and site of BMD measurement to define
osteoporosis. Its usage is also limited in individuals without apparent risk
factors. These limitations should be noted by physicians considering the use of
OSTA in clinical setting. As a conclusion, OSTA is a cost-effective measure for
osteoporosis screening in primary healthcare setting.
PMID- 28695763
TI - Prediction and tolerance intervals for dynamic treatment regimes.
AB - We develop and evaluate tolerance interval methods for dynamic treatment regimes
(DTRs) that can provide more detailed prognostic information to patients who will
follow an estimated optimal regime. Although the problem of constructing
confidence intervals for DTRs has been extensively studied, prediction and
tolerance intervals have received little attention. We begin by reviewing in
detail different interval estimation and prediction methods and then adapting
them to the DTR setting. We illustrate some of the challenges associated with
tolerance interval estimation stemming from the fact that we do not typically
have data that were generated from the estimated optimal regime. We give an
extensive empirical evaluation of the methods and discussed several practical
aspects of method choice, and we present an example application using data from a
clinical trial. Finally, we discuss future directions within this important
emerging area of DTR research.
PMID- 28695764
TI - Laryngeal Cysts in Adults: Simplifying Classification and Management.
AB - Objective Laryngeal cysts may occur at any mucosa-lined location within the
larynx and account for 5% to 10% of nonmalignant laryngeal lesions. A number of
proposed classifications for laryngeal cysts exist; however, no previously
published classification aims to guide management. This review analyzes
contemporary laryngeal cyst management and proposes a framework for the
terminology and management of cystic lesions in the larynx. Data Sources
PubMed/Medline. Review Methods A primary literature search of the entire Medline
database was performed for all titles of publications pertaining to laryngeal
cysts and reviewed for relevance. Full manuscripts were reviewed per the
relevance of their titles and abstracts, and selection into this review was
according to their clinical and scientific relevance. Conclusion Laryngeal cysts
have been associated with rapid-onset epiglottitis, dyspnea, stridor, and death;
therefore, they should not be considered of little significance. Symptoms are
varied and nonspecific. Laryngoscopy is the primary initial diagnostic tool.
Cross-sectional imaging may be required, and future use of endolaryngeal
ultrasound and optical coherence tomography may revolutionize practice. Where
possible, cysts should be completely excised, and there is growing evidence that
a transoral approach is superior to transcervical excision for nearly all cysts.
Histology provides definitive diagnosis, and oncocytic cysts require close follow
up. Implications for Practice A new classification system is proposed that
increases clarity in terminology, with the aim of better preparing surgeons and
authors for future advances in the understanding and management of laryngeal
cysts.
PMID- 28695765
TI - The redundancy effect in human causal learning: No evidence for changes in
selective attention.
AB - Several recent papers have reported a difference in associative learning for two
kinds of redundant cues, such that a blocked cue (e.g., X in A+ AX+) apparently
forms a stronger association with the outcome than an uncorrelated cue (e.g., Y
in BY+ CY-). This difference is referred to as the redundancy effect, and is of
interest because it is contrary to the predictions of a number of popular
learning models. One way of reconciling these models with the redundancy effect
is to assume that the amount of attention paid to redundant cues changes as a
result of experience, and that these changes in attention influence subsequent
learning. Here, we present two experiments designed to evaluate this idea, in
which we measured overt attention using an eye tracker while participants
completed a learning task that elicited the redundancy effect. In both
experiments, gaze duration was longer for uncorrelated cues than for blocked
cues, but this difference disappeared when we divided gaze durations by trial
durations. In Experiment 2, we failed to observe any difference in gaze duration
when blocked and uncorrelated cues were subsequently presented together. While
the observed difference in gaze duration for the two types of redundant cue may
contribute to differences in learning during initial training, we suggest that
the principal causes of the redundancy effect are likely to lie elsewhere.
PMID- 28695766
TI - Endoscopic Management of Paranasal Sinus Mucoceles: Meta-analysis of Visual
Outcomes.
AB - Objective Paranasal sinus mucoceles are benign cystic lesions originating from
sinus mucosa that can impinge on adjacent orbital structures, causing ophthalmic
sequelae such as decreased visual acuity. Definitive treatment requires surgery.
We present the first meta-analysis quantifying the effect of preoperative visual
function and time to surgery on postoperative visual acuity outcomes. Data
Sources PubMed, Ovid, Embase, Web of Science, and the Cochrane Library. Methods
Two independent authors systematically reviewed articles describing outcomes
after endoscopic sinus surgery for paranasal sinus mucoceles presenting with
visual loss. Available data from case reports and series were combined to analyze
the associations among preoperative visual acuity, time to surgery, and
postoperative outcomes. Results Eighty-five studies were included that provided
data on 207 patients. The average presenting visual acuity was 1.57 logMAR
(logarithm of the minimum angle of resolution), and the average postoperative
visual acuity was 0.21 logMAR, with visual improvement in 71.5% of cases.
Preoperative visual acuity >=1.52 logMAR correlated with postoperative
improvement >1 logMAR ( R = 0.4887, P < .0001). A correlation was found between a
time to surgery <6 days and postoperative improvement ( R = 0.297, P < .0001).
Receiver operator curve analysis of these thresholds demonstrated a moderately
accurate prognostic ability (area under the curve: 75.1 for preoperative visual
acuity and 73.1 for time to surgery). Conclusion Visual loss resulting from
paranasal sinus mucoceles is potentially reversible in most cases, even those
presenting with poor vision. When possible, surgery should be performed promptly
after diagnosis, but emergency surgery does not appear to be necessary for vision
restoration.
PMID- 28695767
TI - Treatment of Recurrent Eczematous External Otitis with Honey Eardrops: A Proof-of
Concept Study.
AB - Eczematous external otitis is a chronic inflammatory disease and often difficult
to treat. Our objective was to investigate the clinical effect and in vitro
antibacterial potential of medical honey eardrops as treatment of eczematous
external otitis. In a prospective study, 15 patients diagnosed with recurrent
eczematous external otitis were treated with medical honey eardrops for 2 weeks.
The following clinical outcomes were evaluated: visual analog scale of ear
complaints, score of eczema, and eradication of bacterial infection. Furthermore,
the antibacterial effect of honey eardrops against different bacterial strains
was tested in vitro. Treatment resulted in less discomfort and itching and
decreased signs of eczema, with high patient satisfaction and without adverse
reactions. Honey eardrops showed a strong in vitro inhibitory activity against
all tested strains but did not eradicate Staphylococcus aureus infection in vivo.
The results of this preliminary study indicate a possible role of honey eardrops
in eczematous ear disease.
PMID- 28695768
TI - Expression of Oligodendrocyte Marker during Peripheral-Central Transitional Zone
Formation of the Postnatal Mouse Cochlear Nerve.
AB - Objective To better understand oligodendrocyte protein expression along the mouse
cochlear nerve in postnatal mice. Study Design In vivo murine study. Setting
Research laboratory. Subjects and Methods Swiss Webster mice used at multiple
postnatal days (0, 1, 3, 5, 7, 8, 10, 14, 30, and 60). There were 5 replicates at
each postnatal day. Cryosection was done to produce sections that included the
cochlear nucleus, cochlear nerve, and cochlea in a single sample. Differential
interference contrast (DIC) microscopy and immunofluorescence with antibodies
specific to the oligodendrocyte protein Olig2 were used to study the cochlear
nerve of Swiss Webster mice at postnatal days. Results The myelination of central
nervous system projections initiates in close proximity to the peripheral nervous
system-central nervous system transitional zone (PCTZ), and oligodendrocytes in
neonatal mice are seen with immunohistochemistry peripheral to the DIC-PCTZ
interface. Conclusions As the PCTZ migrates from the brain to the cochlea,
oligodendrocytes are a part of peripheral extension of central nervous system
tissue along the cochlear nerve. Expression of oligodendrocyte marker Oligo2 was
observed peripherally to the formation of PCTZ, as determined by DIC microscopy.
PMID- 28695769
TI - Corrigendum.
AB - Poteet PS, Cox MD, Wang RA, Fitzgerald RT, Kanaan A. Analysis of the relationship
between the location of the anterior ethmoid artery and Keros classification
[published online ahead of print March 28, 2017]. Otolaryngol Head Neck Surg.
(Original doi:10.1177/0194599817696302).
PMID- 28695770
TI - NIH Funding within Otolaryngology: 2005-2014.
AB - Objective Analyze grants awarded between 2005 and 2014 to otolaryngology
departments that appear in the National Institutes of Health (NIH) RePORTER
database, summarize characteristics of grant recipients associated with
otolaryngology departments as listed in the RePORTER between 2005 and 2014, and
identify trends in otolaryngology NIH funding between 2005 and 2014 by topic.
Study Design Case series. Setting NIH database inquiry. Subjects Grant
recipients. Methods The RePORTER was queried for all grants awarded to
otolaryngology departments between 2005 and 2014. All grants classified as new,
renewal, or revision were included while duplicates were excluded. Results In
total, 475 grants to 51 institutions were categorized by topic and subtopic.
Internet searches were conducted for characteristics of 352 principal
investigators. Sixty-seven percent of awardees had a PhD, 22% had an MD, and 11%
had an MD/PhD. Sex ratios varied by degrees held. Although 31% of all grant
recipients were women, this ratio was not seen when recipients were classified by
degree type, with 78% of women holding a PhD compared with 55% of men ( P =
.0013). Of the award types, 39% were R01s, 15% were R21s, and 10% were R03s. The
top 3 represented topics were otology/neurotology (52%), audiology (25%), and
head and neck surgery (14%). The mean annual award amount, after adjusting for
inflation to 2014 dollars, was $226,495.76, with 72.8% awarded by the National
Institute of Deafness and Communication Disorders. Twenty percent of awardees
received multiple grants. Conclusion NIH funding in otolaryngology tends to be
awarded to those with PhDs studying the hearing sciences, with 1 in 5 having
multiple awards. As in other areas of NIH funding, women are underrepresented
overall.
PMID- 28695771
TI - MicroRNA-200b suppresses the invasion and migration of hepatocellular carcinoma
by downregulating RhoA and circRNA_000839.
AB - MicroRNAs could mediate the targeted coding gene and the targeted non-coding RNA
to form endogenous competition, which have an important regulatory role in
tumorigenesis of many types of cancer, including hepatocellular carcinoma. The
goal of this study was to characterize the role of miR-200b in the pathogenesis
of hepatocellular carcinoma. We identified miR-200b that was predicted to
regulate RhoA and circ_000839. Our data establish that miR-200b is expressed at a
relatively low level in hepatocellular carcinoma ( p < 0.001). RhoA and
circ_000839 are expressed at a relatively high level in hepatocellular carcinoma
( p < 0.001, respectively). Our mechanistic data indicate that RhoA is a direct
target of miR-200b ( p < 0.001), binding of which affects the expression of
invasion and migration in hepatocellular carcinoma cell lines ( p < 0.05). And
correlation analysis showed that miR-200b was inversely correlated with RhoA and
circ_000839 ( p = 0.012, p = 0.002, respectively), while RhoA was positively
correlated with circ_000839 ( p < 0.001). Taken together, our data suggest that
miR-200b could mediate RhoA gene and circ_000839 to form endogenous competition.
And this is a direction for the association study of miR-200b and RhoA in the
future.
PMID- 28695772
TI - Circular RNA GLI2 promotes osteosarcoma cell proliferation, migration, and
invasion by targeting miR-125b-5p.
AB - Circular RNAs are novel identified type of endogenous non-coding RNAs, which
exert vital functions in human and animals. However, the in-depth role of
circular RNAs in the progression of tumorigenesis, especially osteosarcoma, is
still undefined. Our preliminary study had found that cir-GLI2 was significantly
upregulated in osteosarcoma tissues compared to adjacent non-tumor tissue.
Moreover, cir-GLI2 silencing could effectively suppress the proliferation,
migration, and invasion capacity of osteosarcoma cells, indicating the tumor
promoting role. Besides, bioinformatics analysis and luciferase reporter assay
predicted the direct binding to miR-125b-5p, which has been reported to function
as a tumor suppressor in osteosarcoma. Furthermore, functional experiments
validated that cir-GLI2 exerted the tumor-promoting effects on osteosarcoma cells
via negatively targeting miR-125b-5p. In conclusion, our study demonstrated that
cir-GLI2 acts as an oncogenic circular RNA in osteosarcoma genesis, providing a
novel diagnostic and therapeutic target for osteosarcoma.
PMID- 28695773
TI - Polymorphisms of the receptor for advanced glycation end products and glyoxalase
I and long-term outcome in patients with breast cancer.
AB - Receptor for advanced glycation end products and glyoxalase I metabolizing
advanced glycation end product precursors may play important role in the
pathogenesis and progression of cancer. Potential relation between soluble forms
of receptor for advanced glycation end products (sRAGE), receptor for advanced
glycation end products, glyoxalase I polymorphisms, and long-term outcome (median
follow-up of 10.3 years) was studied in 116 patients with breast cancer. Gly82Ser
and 2184 A/G RAGE polymorphisms were related to the mortality due to the breast
cancer and -419 A/C glyoxalase I polymorphism was related to the overall
mortality of the patients suggesting their role not only in the risk of breast
cancer but also in the outcome of patients with breast cancer.
PMID- 28695774
TI - Regulatory risk assessments: Is there a need to reduce uncertainty and enhance
robustness? Update on propylparaben in relation to its EU regulatory status.
AB - Over 10 years ago, propylparaben (propyl- p-hydroxybenzoate; PP) was withdrawn as
a permitted food preservative in the EU based entirely on findings reported in a
single dietary study in juvenile rats claiming to show adverse effects on male
reproductive parameters [Oishi S. Effects of propyl paraben on the male
reproductive system. Food Chem Toxicol 2002; 40(12): 1807 -1813]. Subsequent data
reviews have cast serious doubt on the validity of the Oishi results, mainly in
relation to aberrant concurrent-control values, and in two further comprehensive
studies using neonatal and juvenile rats there were no adverse effects in males
at oral doses up to 1000 mg/kg/day. By contrast, juvenile animal toxicity data on
the two paraben preservatives currently permitted in the EU as food additives
(methylparaben and ethylparaben) are non-robust and rudimentary. Although PP is a
permitted preservative in cosmetics its use pattern is highly restricted based
mainly on the results of a screening study in the rat using butylparaben as test
material, and not taking into account the more recent data on PP. The European
Medicines Agency has determined a permitted daily exposure of 2 mg/kg for PP,
which applies to both adult and paediatric patients, based on an oral no-observed
adverse-effect level of 100 mg/kg/day in females, treatment-related changes
suggestive of an estrogenic effect being noted at 1000 mg/kg/day. The weight of
evidence strongly supports a toxicological re-evaluation of PP regarding its use
in foodstuffs and cosmetics in the EU, with a view to reinstatement as a food
additive, consistent with its status in other major jurisdictions.
PMID- 28695775
TI - A qualitative study on the implementation of quality systems in Australian
hospitals.
AB - Public hospitals are required to have quality systems in place to meet
accreditation standards, achieve government performance expectations and
continually improve care. However, previous study suggests that there has been
limited success in the implementation of effective quality systems. Using
document review, self-evaluation and qualitative data from interviews and focus
groups of 270 board members, managers and staff we explored the implementation of
quality systems in eight Australian public hospitals. Using normalisation process
theory, we found that the hospitals took a technical, top-down approach to
quality system implementation and did not provide staff with opportunities for
socialization of the technology that enabled them to normalise the quality work.
'Quality' was consistently described as an 'extra' set of tasks to do, rather
than a means to creating sustained, safe, quality care. Despite enormous goodwill
and positive intent, a lack of understanding of how to effect change in the
complexity of hospitals has led the boards and senior managers in our sample to
execute a technical, top-down approach based on compliance and reactive risk.
PMID- 28695776
TI - Chemical Characterization and Determination of the Anti-Oxidant Capacity of Two
Brown Algae with Respect to Sampling Season and Morphological Structures Using
Infrared Spectroscopy and Multivariate Analyses.
AB - Brown algae biomass has been shown to be a highly important industrial source for
the production of alginates and different nutraceutical products. The
characterization of this biomass is necessary in order to allocate its use to
specific applications according to the chemical and biological characteristics of
this highly variable resource. The methods commonly used for algae
characterization require a long time for the analysis and rigorous pretreatments
of samples. In this work, nondestructive and fast analyses of different
morphological structures from Lessonia spicata and Macrocystis pyrifera, which
were collected during different seasons, were performed using Fourier transform
infrared (FT-IR) techniques in combination with chemometric methods. Mid-infrared
(IR) and near-infrared (NIR) spectral ranges were tested to evaluate the spectral
differences between the species, seasons, and morphological structures of algae
using a principal component analysis (PCA). Quantitative analyses of the
polyphenol and alginate contents and the anti-oxidant capacity of the samples
were performed using partial least squares (PLS) with both spectral ranges in
order to build a predictive model for the rapid quantification of these
parameters with industrial purposes. The PCA mainly showed differences in the
samples based on seasonal sampling, where changes were observed in the bands
corresponding to polysaccharides, proteins, and lipids. The obtained PLS models
had high correlation coefficients (r) for the polyphenol content and anti-oxidant
capacity (r > 0.9) and lower values for the alginate determination (0.7 < r <
0.8). Fourier transform infrared-based techniques were suitable tools for the
rapid characterization of algae biomass, in which high variability in the samples
was incorporated for the qualitative and quantitative analyses, and have the
potential to be used on an industrial scale.
PMID- 28695777
TI - The limited impact that cocaine use patterns have on neurocognitive functioning
in individuals with cocaine use disorder.
AB - It is well-documented in the literature that cocaine use is associated with
neurocognitive impairment. The manner in which patterns of cocaine use, such as
years of use, recent use over the past month, and daily amount of cocaine use,
moderate neurocognition has been studied in a relatively piecemeal manner. Hence,
the purpose of the study was to evaluate whether cocaine use patterns modulate
neurocognition in individuals with cocaine use disorder. Cocaine users who were
cocaine-negative ( n=125) were divided into tertiles based on cocaine use
patterns and the performances of the highest and lowest groups were compared on
the following cognitive measures: Continuous Performance Task-II, n-back, and
Hopkins Verbal Learning Task-Revised. Participants with cocaine use disorder who
used for more years (25.2+/-0.6 versus 10.1+/-0.6 years; mean+/-standard error of
the mean) and who had more recent cocaine use over the past month (26.3+/-0.5
versus 6.0+/-0.6 days) did not differ significantly on any of the neurocognitive
variables when compared to those with use patterns of shorter duration and less
frequency (all p's >0.05). Lastly, participants reporting the greatest amount
daily cocaine use (1.8+/-0.0 g) demonstrated better performance on an auditory
working memory task when compared to those with the lowest daily use (0.7+/-0.0
g; p=0.04). While one might expect that individuals who used greater amounts of
cocaine over longer periods of time would demonstrate relatively poorer
performance on measures of neurocognition, particularly in the initial phase of
abstinence, our findings did not confirm this. While speculative, a potential
explanation for these findings is that after an individual uses cocaine for a
certain number of years, or uses a specific amount over time, then the
deleterious effects of cocaine on neurocognition stabilizes, and increased
duration of cocaine use does not further exacerbate those impairments.
PMID- 28695778
TI - W. Bruce Conolly 1 February 1935-21 February 2017.
PMID- 28695779
TI - Hand surgery in Finland.
PMID- 28695781
TI - How to get a manuscript published.
PMID- 28695783
TI - Sialendoscopic Pneumatic Lithotripsy for Salivary Calculi: A New Technique and a
Long-term Clinical Experience.
AB - We report our results comprising a series of 34 cases of sialolithiasis that were
approached sialendoscopically with conventional instruments (ie, basket and/or
forceps) and for which stone removal was unsuccessful and so were thereafter
treated with pneumatic lithotripsy. Intraductal pneumatic lithotripsy was able to
fragment 30 of 34 (88%) salivary calculi in total. No major complications
occurred. All 30 treated glands returned to normal function without any symptoms.
We believe that the success of sialendoscopy is closely related to the success of
salivary stone fragmentability.
PMID- 28695784
TI - Provision of powered communication aids in the United Kingdom.
AB - AAC service provision in the United Kingdom (UK) has evolved since the first
service dedicated to the provision of communication aids opened in 1986. Within
the UK, many health and care services are provided via government funding;
however, the assessment and provision of AAC and specifically of speech
generating devices (SGDs) is inconsistent and inequitable. The study reported in
this paper aimed to collect information on levels of current provision of powered
communication aids (the term used in the study to refer to SGDs) by UK service
providers in 2013 with the intention of improving future estimates for need of
services. A questionnaire survey was designed and data were obtained from 98 AAC
services across the UK. Service providers reported the number of individuals
known to be using powered communication aids and the mean value reported was
0.0155% of the services' catchment populations. However levels of service
provision reported were highly variable. Although the data reported must be
treated with caution, it adds to the sparse literature on the topic, informs AAC
service design and delivery in the UK, and acts as an indicative baseline measure
for future service development.
PMID- 28695785
TI - CT Study of the Arytenoid Cartilage in Patients with Laryngeal Contact Granuloma.
AB - Objective To explore high-resolution computed tomography (HRCT) characteristics
of arytenoid cartilage in patients with laryngeal contact granuloma (LCG).
Setting Tertiary hospitals. Study Design Individual case-control study. Methods
HRCT scans were obtained before treatment from 42 patients with LCG. Similar
scans were obtained from 50 patients with glottic laryngeal cancer or vocal cord
leukoplakia without vocal process involvement. Results Forty-two male patients
with LCG were enrolled in the study. There were 41 patients with unilateral vocal
cord lesions, and 1 patient had bilateral lesions. All 50 eligible patients in
the laryngeal lesion group were men. There were 39 patients with unilateral
lesions, and 11 had bilateral lesions. The rate of arytenoid cartilage sclerosis
in the LCG group was 79.07% (34/43) on the lesion side and 7.32% (3/41) on the
healthy side. In the laryngeal lesion group, the rate of arytenoid cartilage
sclerosis was 13.11% (8/61) on the lesion side and 2.56% (1/39) on the healthy
side. The rate of arytenoid cartilage sclerosis on the lesion side of patients
with LCG was significantly higher than on the healthy side of patients with LCG
and significantly higher than both the healthy and lesion sides of patients with
laryngeal lesions ( P < .001). Conclusions Arytenoid cartilage sclerosis was
observed on the lesion side in most patients with LCG, and the presence of
sclerosis may support the diagnosis of LCG.
PMID- 28695786
TI - Antibiotic Prophylaxis in Clean-Contaminated Head and Neck Surgery: A Systematic
Review and Meta-analysis.
AB - Objective To determine the optimal duration and type of antibiotic prophylaxis in
patients undergoing clean-contaminated resection for head and neck cancer. Data
Sources Search strategies were created by a medical librarian, implemented in
multiple databases, and completed in June 2016. Review Methods The population of
interest was adults >=18 years undergoing clean-contaminated head and neck
surgery, intervention was postoperative antibiotic prophylaxis, comparator was
duration and types of antibiotics used, outcome was the wound infection rate, and
the study design was randomized controlled trials (RCTs). Studies were excluded
if not randomized, did not use systemic antibiotics, did not study wound
infections, or included children. After excluding duplicates, the search strategy
yielded 427 abstracts. After applying inclusion and exclusion criteria, 67
studies were screened, leaving 19 RCTs for review. PRISMA guidelines were
followed. A random-effects model was used for meta-analysis. Results Meta
analysis of 340 patients in 4 RCTs showed that the pooled relative risk of wound
infection was 0.98 (95% confidence interval [CI], 0.58-1.61; P = .718; I2 = 0.0%)
in patients receiving 1 day vs 5 days of prophylaxis. Conclusion This study
provides evidence that there is no difference in the risk of wound infection with
1 day vs 5 days of systemic antibiotic prophylaxis in clean-contaminated head and
neck surgery, consistent with existing guidelines. Future large randomized trials
are needed to more clearly define the appropriate choice of prophylaxis in
penicillin-allergic patients.
PMID- 28695787
TI - Spontaneous remission of acute myeloid leukemia after discontinuation of
lenalidomide.
PMID- 28695788
TI - Adherence to Clinical Practice Guidelines.
AB - Clinical practice guidelines are designed to synthesize and disseminate the best
available evidence to guide clinical practice. The goal is to increase high
quality care and reduce inappropriate interventions. Clinical practice guidelines
that systematically review evidence and synthesize it into recommendations are
important because the available scientific evidence is normally neither rapidly
nor broadly incorporated into practice. It is important to understand and improve
the impact of our American Academy of Otolaryngology-Head and Neck Surgery
Foundation clinical practice guidelines on this uptake of scientific knowledge.
Considering the barriers to guideline adherence is a central part of this. This
understanding can guide clinicians, future guideline authors, and researchers
when using guidelines, writing them, and planning clinically relevant research.
PMID- 28695789
TI - Addressing a Major Health Problem From an Array of Perspectives.
PMID- 28695790
TI - Midwest Nursing Research Society News.
PMID- 28695791
TI - Lutein and Zeaxanthin Influence Brain Function in Older Adults: A Randomized
Controlled Trial.
AB - OBJECTIVES: The present study constitutes the first randomized controlled trial
to investigate the relation of lutein (L) and zeaxanthin (Z) to brain function
using functional magnetic resonance imaging (fMRI). It was hypothesized that L
and Z supplementation in older adults would enhance neural efficiency (i.e.,
reduce activation) and cognitive performance on a verbal learning task relative
to placebo. METHODS: A total of 44 community-dwelling older adults (mean age=72
years) were randomly assigned to receive either placebo or L+Z supplementation
(12 mg/daily) for 1 year. Neurocognitive performance was assessed at baseline and
post-intervention on an fMRI-adapted task involving learning and recalling word
pairs. Imaging contrasts of blood-oxygen-level-dependent (BOLD) signal were
created by subtracting active control trials from learning and recall trials. A
flexible factorial model was employed to investigate the expected group (placebo
vs. supplement) by time (baseline vs. post-intervention) interaction in pre
specified regions-of-interest. RESULTS: L and Z appeared to buffer cognitive
decline on the verbal learning task (Cohen's d=.84). Significant interactions
during learning were observed in left dorsolateral prefrontal cortex and anterior
cingulate cortex (p < .05, family-wise-error corrected). However, these effects
were in the direction of increased rather than decreased BOLD signal. Although
the omnibus interaction was not significant during recall, within-group contrasts
revealed significant increases in left prefrontal activation in the supplement
group only. CONCLUSIONS: L and Z supplementation appears to benefit
neurocognitive function by enhancing cerebral perfusion, even if consumed for a
discrete period of time in late life. (JINS, 2018, 24, 77-90).
PMID- 28695792
TI - Prediction of foal carcass composition and wholesale cut yields by using video
image analysis.
AB - This work represents the first contribution for the application of the video
image analysis (VIA) technology in predicting lean meat and fat composition in
the equine species. Images of left sides of the carcass (n=42) were captured from
the dorsal, lateral and medial views using a high-resolution digital camera. A
total of 41 measurements (angles, lengths, widths and areas) were obtained by
VIA. The variation of percentage of lean meat obtained from the forequarter (FQ)
and hindquarter (HQ) carcass ranged between 5.86% and 7.83%. However, the
percentage of fat (FAT) obtained from the FQ and HQ carcass presented a higher
variation (CV between 41.34% and 44.58%). By combining different measurements and
using prediction models with cold carcass weight (CCW) and VIA measurement the
coefficient of determination (k-fold-R 2) were 0.458 and 0.532 for FQ and HQ,
respectively. On the other hand, employing the most comprehensive model (CCW plus
all VIA measurements), the k-fold-R 2 increased from 0.494 to 0.887 and 0.513 to
0.878 with respect to the simplest model (only with CCW), while precision
increased with the reduction in the root mean square error (2.958 to 0.947 and
1.841 to 0.787) for the hindquarter fat and lean percentage, respectively. With
CCW plus VIA measurements is possible to explain the wholesale value cuts yield
variation (k-fold-R 2 between 0.533 and 0.889). Overall, the VIA technology
performed in the present study could be considered as an accurate method to
assess the horse carcass composition which could have a role in breeding
programmes and research studies to assist in the development of a value-based
marketing system for horse carcass.
PMID- 28695793
TI - Genetic relationship between weaning weight and milk yield in Nguni cattle.
AB - A study was conducted to estimate the genetic relationship between weaning weight
and milk yield in Nguni cattle. Milk yield data (n=125) were collected from 116
Nguni cows from Mara Research Station located in Limpopo Province and Loskop
South Farm located in Mpumalanga Province using the weigh-suckle-weigh technique.
Weaning weight data (n=19 065) were obtained from stud Nguni cattle from 146
herds distributed throughout South Africa. Estimates of (co)variance components
for milk yield and weaning weight were calculated using PEST and VCE softwares.
The average weaning weight, age of the calf at weaning and 24-h milk yield was
158.94 kg, 210 days and 5.25 kg/day, respectively. Heritability estimates for
milk yield, direct and maternal weaning weight were 0.22+/-0.238, 0.47+/-0.039
and 0.25+/-0.029, respectively. Estimates of genetic correlations for milk yield
and maternal weaning weight, milk yield and direct weaning weight, direct and
maternal weaning weight were 0.97+/-0.063, -0.71+/-0.416 and -0.56+/-0.247,
respectively. The results indicate that maternal weaning weight is genetically
highly predictive of milk yield in Nguni cattle. Maternal breeding values for
weaning weight could therefore be used as a selection criterion to improve milk
yield in Nguni cattle.
PMID- 28695794
TI - WITHDRAWN: The Natural Component Isolated From Enterolobium contortisiliquum
Impairs Brain Tumors and Affects Their Interactions With Mesenchymal Stem Cells.
AB - Ahead of Print article withdrawn by publisher.
PMID- 28695795
TI - Pharmacologic Inhibition of beta-Catenin With Pyrvinium Inhibits Murine and Human
Models of Wilms Tumor.
AB - Wilms tumor (WT) is the most common renal malignancy in children and the fourth
most common pediatric solid malignancy in the US. Although the mechanisms
underlying the WT biology are complex, these tumors most often demonstrate
activation of the canonical Wnt/beta-catenin pathway. We and others have shown
that constitutive activation of beta-catenin restricted to the renal epithelium
is sufficient to induce primitive renal epithelial tumors, which resemble human
WT. Here we demonstrate that pharmacologic inhibition of beta-catenin gene
transcription with pyrvinium inhibits tumor growth and metastatic progression in
a murine model of WT. Cellular invasion is significantly inhibited in both murine
WT-like and human WT cells and is accompanied by downregulation of the oncogenes
Myc and Birc5 (survivin). Our studies provide proof of the concept that the
canonical Wnt/beta-catenin pathway may be a novel therapeutic target in the
management of WT.
PMID- 28695796
TI - Purification and characterization of adenovirus core protein VII: a histone-like
protein that is critical for adenovirus core formation.
AB - Adenovirus protein VII is a highly cationic core protein that forms a nucleosome
like structure in the adenovirus core by condensing DNA in combination with
protein V and mu. It has been proposed that protein VII could condense DNA in a
manner analogous to mammalian histones. Due to the lack of an expression and
purification protocol, the interactions between protein VII and DNA are poorly
understood. In this study we describe methods for the purification of
biologically active recombinant protein VII using an E. coli expression system.
We expressed a cleavable fusion of protein VII with thioredoxin and established
methods for purification of this fusion protein in denatured form. We describe an
efficient method for resolving the cleavage products to obtain pure protein VII
using hydroxyapatite column chromatography. Mass spectroscopy data confirmed its
mass and purity to be 19.4 kDa and >98 %, respectively. Purified recombinant
protein VII spontaneously condensed dsDNA to form particles, as shown by dye
exclusion assay, electrophoretic mobility shift assay and nuclease protection
assay. Additionally, an in vitro bioluminescence assay revealed that protein VII
can be used to enhance the transfection of mammalian cells with lipofectamine/DNA
complexes. The availability of recombinant protein VII will facilitate future
studies of the structure of the adenovirus core. Improved understanding of the
structure and function of protein VII will be valuable in elucidating the
mechanism of adenoviral DNA condensation, defining the morphology of the
adenovirus core and establishing the mechanism by which adenoviral DNA enters the
nucleus.
PMID- 28695797
TI - Effects of 630 nm Red and 460 nm Blue Light Emitting Diode Irradiation on Healing
of the Skin Wound in Japanese Big-ear White Rabbit.
AB - Objective To observe the effects of 630 nm red light and 460 nm blue light
emitting diode irradiation on the healing of skin wounds in Japanese big-ear
white rabbits. Methods The skin wound model was established with 8 Japanese big
ear white rabbits. Three parts of vulnus in each rabbit were used:two parts of
vulnus were irradiated vertically by red and blue LED light,respectively(15
min/time),and the distance between lights and wounds was 15 cm;the 3rd part of
the wound was used as a control. On the 21st day of the wounds exposure to
light,the number of healing wounds and the percentage of healing area were
recorded and the treatment effect of these two light sources was compared. HE
staining was used to analyze the newborn tissue structure. Masson staining was
used to observe the proliferation of skin collagen fibers. Immuohistochemical
staining was used to analyze fibroblast growth factor(FGF),epidermal growth
factor(EGF),endothelial growth factor(CD31),proliferating cell nuclear antigen(Ki
67),and inflammatory cytokines(CD68)infiltration in the skin. Results The healing
rate in the red light,blue light,and control groups was 50.0%(4/8),25.0%(2/8),and
12.5%(1/8),respectively. Since the 12th day after modeling,the healing area
percentage in the red light group was significantly higher than those in the blue
light and control groups(P<0.05,P<0.01). On the 21st day after modeling,the skin
thickness of the red light group was(2.95+/-0.34)mm,which was significantly
higher than that in control group [(2.52+/-0.42)mm;F=3.182,P=0.016)]. The average
optical density of collagen fibers was 0.15+/-0.03 in red light group,which was
significantly higher than that of the blue light group(0.09+/
0.01;F=7.316,P=0.012)and control(0.07+/-0.01;F=7.316,P=0.003). The results of
immunohistochemistry showed the expression levels of EGF,FGF,CD31 antigen,and Ki
67 in the red light group were significantly higher than those in the blue light
and control groups,whereas the CD68 expression was significantly lower(P<0.05 or
P<0.01). Conclusion LED red light irradiation can promote the healing of skin
wounds in Japanese big-ear white rabbits,which may be achieved by the effect of
red light irradiation in stimulating the proliferation of skin epidermal
cells,vascular endothelial cells,and fiberous tissue.
PMID- 28695798
TI - Hippocampal Apoptosis and Cognitive Function in Dysbindin-1B+/+ Mice.
AB - Objective To explore the apoptosis in the hippocampus of dysbindin-1B+/+ mice and
the behaviors of 4-month-old dysbindin-1B+/+ mice and wild-type mice. Methods The
hippocampus of dysbindin-1B+/+ mice and corresponding wild-type mice were
assessed by TUNEL assay and transmission electron microscopy. Then twelve 4-month
old male dysbindin-1B+/+ mice and twelve wild-type mice were enrolled. The open
field and T maze test were conducted to observe locomotor activity,exploratory
behaviors,and spatial memory. Result TUNEL+ neurons were found in hippocampus of
dysbindin-1B+/+ mice,especially in dentate gyrus region,but not in that of wild
type mice(t=12.98,P<0.0001). Transmission electron microscopy showed the presence
of middle-and late-stage apoptosis in the hippocampus of dysbindin-1B+/+
mice,while there was no apoptosis in wild-type mice. Open field test showed
that,compared with the moving distance of wild-type mice [(3632+/
606)cm],dysbindin-1B+/+ mice presented significantly lower moving distances
[(2887+/-376)cm] (t=2.993,P=0.0122). Meanwhile,compared with the moving time of
wild-type mice in the central area [(114.00+/-34.09)s],dysbindin-1B+/+ mice
presented lower moving time [(64.22+/-14.67)s] (t=4.649,P=0.0023). T maze test
showed that when the interval between forced run and test run were 60 s and 180
s,respectively,the accuracy of dysbindin-1B+/+ was (70.40+/-15.17)% and (59.28+/
9.10)%,which was significantly lower than those of wild type mice (91.67+/
13.94)% (t=3.261,P=0.0258) and (83.33+/-14.89)% (t=3.687,P=0.0291);when the
interval was 15 s,there was no significant difference between these two groups
[100% vs.(94.45+/-6.08)%; t=0.851,P=0.0756]. Conclusion Dysbindin-1B+/+
expression can cause the apoptosis of neurons,which may cause anxious behavior
and impair the locomotor activity and spatial memory.
PMID- 28695799
TI - Effect of Human Hepatocellular Carcinoma HepG2 Cell-derived Exosome on the
Differentiation of Mesenchymal Stem Cells and Their Interaction.
AB - Objective To investigate the effect of human hepatocellular carcinoma HepG2 cell
derived Exosome on the differentiation of mesenchymal stem cells(MSC)into cancer
associated myofibroblasts(CAF)and the impacts of CAF on liver cancer cell
proliferation,migration,and invasion. Methods The protein expression of HepG2
cell-derived Exosome was detected by Western blotting. MSCs were separated from
human adipose tissue and cultured with HepG2 cell-derived Exosome(100 ng/nl)to
initiate differentiation. The expressions of mesenchymal markers and several
interleukins were also detected by Western blotting. HepG2 cells were co-cultured
with the conditioned media(CM),in which HepG2 Exosome induced the differentiation
of MSC into CAF. The expressions of epithelial and mesenchymal markers were
detected by real-time polymerase chain reaction(PCR)and Western blotting. Cell
proliferation was assessed using MTS assay. Transwell chambers were used in the
in vitro migration and invasion assay. Results HepG2 cell-derived particles
expressed CD63,70 kilodalton heat shock proteins,and 90 kilodalton heat shock
proteins. With the treatment of HepG2 cell-derived Exosome,the expressions of
mesenchymal marker alpha-smooth muscle actin,fibroblast activation protein
alpha,interleukin(IL)-6,IL-8,and IL-1beta were up-regulated,while vascular
endothelial growth factor had no significant change. The conditioned media which
HepG2 Exosome induced MSC differentiation CAF(CAF-CM)could significantly promote
HepG2 cells proliferation(1.075+/-0.104),compared to BSA control(0.874+/
0.066,P=0.023)and MSC-CM(0.649+/-0.034,P=0.0005). CAF-CM could significantly
enhance cell migration [(42.5+/-9.1) cells vs.(18.5+/-3.1) cells,P=0.001] and
invasion [(29.0+/-3.5) cells vs.(13.1+/-3.7) cells,P=0.009] compared to its
control group. Moreover the conditioned medium which HepG2 Exosome induced MSC to
differentiate into CAF could also promote the expressions of mesenchyme-related
genes Smad interacting protein 1(P=0.040),beta
catenin(P=0.038),fibronectin(P=0.029),and Vimentin(P=0.013)and inhibit the
expression of epithelial related genes zonula ocdudens-1(P=0.010).Conclusions
Exosome extracted from HepG2 cells can induce human adipose-derived MSC to
differentiate into cancer-associated myofibroblasts. CAF-like cells can promote
the migration of the liver cancer cell line HepG2.
PMID- 28695800
TI - Application of Recombinant Collagen Type I Combined with Polyaspartic Acid in
Biomimetic Biomineralization.
AB - Objective To prepare biomimetic bone material by reconstructing type I collagen
combined with polyaspartic acid. Methods By acid hydrolysis,rat tail type I
collagen was decomposed into collagen fibers,which were then placed in the
calcium phosphate mineralization solution. Under the cross-linking of
glutaraldehyde,the collagen fibers were reconstructed and assembled into collagen
fibers,and the calcium phosphate crystals were wrapped in the inner side of the
collagen fibers for biomineralizationin. After poly aspartate acid was
added,calcium hydroxyapatite calcium precursor was added into the collagen fibers
to simulate thebiomimetic biomineralizationin the human body. After
mineralization for 3-9 days,the bone mineralization process was observed by
transmission electron microscopy and electron diffraction. Results Transmission
electron microscopy and electron diffraction displayed that,after 3 days of
mineralization,calcium hydroxyapatite precursor was wrapped in the collagen fiber
gap,and the collagen fiber was partially mineralized. After 9 days of
mineralization,calcium hydroxyapatite precursor completely infiltrated into the
collagen fiber,and the amorphous calcium phosphate was transformed into
hydroxyapatite calcium crystal. Thus,the simulation of bone mineralization was
completed,and collagen type I collagen/hydroxyapatite calcium biomimetic bone
material was formed. Conclusion Reconstruction of type I collagen combined with
polyaspartic acid can prepare biomimetic bone material that has close chemical
composition and molecular structure to the human bone tissue.
PMID- 28695801
TI - Establishment and Assessment of Mice Models of Type 2 Diabetes Mellitus.
AB - Objective To establish type 2 diabetes mellitus(T2DM)KM mouse models via the
combined use of high-calorie diet and multiple administration of low-dose
streptozotocin(STZ). Methods Based on the randomized number table,30 KM mice were
equally and randomly divided into 2 groups:modeling group and control group. Mice
in the modeling group were given foods with high calories for one month and
injected with 30 mg/kg STZ via the left lower abdominal cavity for 2-4
consecutive days,while mice in the control group were fed with standard
maintenance foods and the same dose of citrate buffer solution. The general
conditions including food and water intake and mice weight were recorded. Blood
glucose level was measured 1,2,4,5,12,and 21 weeks after STZ injection. When the
glucose level became stabilized,the serum insulin and blood lipids [including
total cholesterol(TC),triacylglycerol(TG),high-density lipoprotein(HDL) and low
density lipoprotein(LDL)],and hemoglobin a1c (HbA1c)were measured,and oral
glucose tolerance test were performed. Results The modeling group had a 100%
survival rate. After STZ injection,the body weight of mice in the modeling group
reached the peak in the forth week,and later the growth rate decreased,still
significantly lower than that of control group mice till the 21st
week(t=3.160,P=0.006). Their blood glucose level was significantly higher than
that of mice before STZ injection and in the control group(all P<0.05);as time
went on,it was also rising,and it remained high till the 21st week [(26.38+/
1.34)mmol/L]. In the 4th week,the fasting blood glucose of mice in the modeling
group was(11.86+/-3.33)mmol/L,which was significantly higher than that of mice in
the control group [(6.37+/-1.27)mmol/L](t=-3.830,P=0.002). Fasting serum insulin
of mice in the modeling group showed no significant difference compared with
control group [(5.73+/-0.24)mU/L vs.(5.48+/-0.32)mU/L;t=-0.863,P=0.416]. Insulin
sensitivity index was 0.0145+/-0.0039,which was significantly lower than
that(0.0267+/-0.0039)in control group(t=4.414,P=0.003). In the 6th week,the blood
glucose levels of mice in the modeling group were(15.35+/-1.82),(26.45+/
1.07),(25.58+/-1.46),and(26.15+/-1.00)mmol/L 0,30,60,and 120 min after oral
gavage of D-glucose,which were all significantly higher than those in the control
group [(6.88+/-1.75)(t=-8.203,P=0.000),(17.65+/-2.94)(t=-6.884,P=0.000),(13.18+/
2.04)(t=-12.110,P=0.000),and(7.37+/-3.40)mmol/L(t=-12.969,P=0.000)]. In the 8th
week,serum TC and TG levels of mice in the modeling group were(3.83+/
0.06)and(2.20+/-0.20)mmol/L,which were significantly higher than those in the
control group [(3.10+/-0.10)(t=11.000,P=0.000)and(0.90+/
0.10)mmol/L(t=10.070,P=0.000)]. HDL level of mice in the modeling group
was(2.03+/-0.06)mmol/L,which was significantly lower than that in the control
group [(2.48+/-0.02)mmol/L;t=11.662,P=0.000]. LDL level was increased but showed
no significant difference [(0.34+/-0.08)mmol/L vs.(0.26+/
0.02)mmol/L](t=1.680,P=0.168). HbA1c content of mice in the modeling group
was(7.30+/-0.31)%,which was significantly higher than that(4.40+/-0.32)% in the
control group(t=-11.587,P=0.000). Conclusion KM mice models of T2DM were
successfully established after high-calorie diet and multiple administration of
low-dose STZ.
PMID- 28695802
TI - Effect of Ganoderma Lucidum Preparation on the Behavior,Biochemistry,and
Autoimmune Parameters of Mouse Models of APP/PS1 Double Transgenic Alzheimer's
Disease.
AB - Objective To evaluate the efficacy of Ganoderma lucidum preparation on the
behaviors,biochemistry,and autoimmunity parameters of mouse models of APP/PS-1
double transgenic Alzheimer's disease(AD).Methods A total of 44 4-month-old
APP/PS-1 double transgenic AD mice were randomly divided into AD model
group,Aricept group,Ganoderma lucidum middle-dose(LZ-M)group,and Ganoderma
lucidum high-dose(LZ-H)group,with 11 mice in each group.In addition,10 4-month
old C57BL/6 mice were used as the control group.Water maze test was conducted to
observe the behavior changes,and the protein expressions in brain tissues were
detected by Western blot analysis.The autoimmune indicators were detected by
indirect immunofluorescence method.Results In the navigation experiment,the time
of finding the platform was gradually shortened since the 2nd day in the
control,LZ-H,and LZ-M groups,and the time of searching the platform in the AD
model group gradually increased.On the 5th day,the time of finding platform was
significantly shorter in control group (t=5.607,P=0.000) and LZ-H
group(t=2.750,P=0.010)than AD model group.In the space exploration experiment,the
number of crossing the target platform(t=2.452,P=0.025)and the residence time in
the target quadrant(t=2.530,P=0.020)in AD model group mice was significantly
smaller/shorter than those in control group;in addition,the number of crossing
the target platform in the AD model group was significantly smaller than that in
LZ-H group(t=2.317,P=0.030)and LZ-M group(t=2.443,P=0.030),while the residence
time in target quadrant decreased significantly(t=2.770,P=0.020)compared with LZ
H group;the number of crossing through the target platform
quadrant(t=2.493,P=0.022)and residence time in the target
quadrant(t=2.683,P=0.015)in LZ-H group were significantly higher than in Aricept
group.Western blot analysis showed that the expression of ApoA1 in the brain
tissues of mice in LZ-H and LZ-M groups were significantly higher than those in
AD model group(P<0.01,P<0.05);Abeta-40 expression in LZ-H group was significantly
lower than that in AD model group(P<0.05);the expressions of Syt1,ApoE,and ABCA1
in brain tissues of mice in LZ-H group were significantly higher than those in
model group(P<0.01,P<0.05).The plasma IgG level in Aricept
group(t=30.945,P=0.000),LZ-M group(t=25.639,P=0.000)and LZ-H
group(t=4.689,P=0.001)were significantly higher than that in the control
group.Conclusion Ganoderma lucidum preparation can improve behavior disorders of
AD model mice,promote the expressions of ApoA1,ApoE and Syt1,inhibit the
expression of Abeta-40 protein,and improve the autoimmune function.
PMID- 28695803
TI - Bioinformatic Analysis of Differentially Expressed Genes in Peripheral Blood of
Human Immunodeficiency Virus/Tubercle Bacilli Co-infected Patients.
AB - Objective To analyze the differentially expressed genes in peripheral blood of
human immunodeficiency(HIV)/tubercle bacilli co-infected patients and explore the
biological regulatory mechanism and network of key proteins,so as to provide new
evidence for early diagnosis and clinical treatment of HIV/TB co-infected
patients. Methods Microarray gene chip data of HIV/TB co-infected patients were
downloaded from public databases GEO and imported into the analysis software
GEO,STRING,PANTHER,and GenClip. The gene expression profiles,protein interaction
networks,processes of molecular biology,and gene functions were analyzed. Results
The expression profiles of 15 529 genes between the two groups of patients were
similar,and gene expression profiles from 44 subjects were highly correlated. The
251 differentially expressed genes had good diagnostic capabilities in the
differential diagnosis of HIV/TB infection. RPLP1 might be a key gene in the
diagnosis of HIV/TB infection. The differentially expressed genes and positive
regulators showed certain functions such as external stimuli,signal transduction
pathways in cells,migration of neutrophils,and immunological and other relevant
functionalities. Meanwhile,they may also be involved in free radical-related
apoptosis,inflammation,and activation pathways. Conclusions A total of 251
differentially expressed genes are found to be able to distinguish simple HIV
infection from HIV/TB infection. Protein-protein interaction network of top 40
differential expression genes includes RPLP1 gene,which is possibly associated
with HIV/TB co-infection and may be involved in and the positive regulation of
external stimuli,signal transduction pathways in cells,migration of
neutrophils,and immunological functions. These findings may provide certain
evidence for the diagnosis and treatment of HIV/TB infection.
PMID- 28695804
TI - Effects of Enhanced Exercise and Combined Vitamin D and Calcium Supplementation
on Muscle Strength and Fracture Risk in Postmenopausal Chinese Women.
AB - Objective To observe the effects of enhanced exercise and combined vitamin D and
calcium supplementation on muscular strength and fracture occurrence in
postmenopausal women with a high risk of osteoporosis.Methods Totally 614
postmenopausal women at high risk factors of osteoporosis were enrolled in
Dongcheng district of Beijing and randomized into four groups:group A(control
group,n=173),group B(regular Tai Chi exercise,n=171),group C(calcium 600
mg/d+VitD3 800 U/d,n=139),and group D[calcium 600 mg/d+25 hydroxyl vitamin
D(25OHD) 0.25 MUg/d,n=131].Muscular strength was measured at baseline and one and
two years after intervention.Bone turnover markers were measured at baseline and
during the two-year follow-up.Falls and fractures were recorded.Results The
incidence of 25OHD<50 nmol/L was approximately 92.6%.During the follow-up,the
left grip strength decreased significantly two years after intervention(t=
3.252,P=0.001)in group A.Right grip strength decreased significantly in group
B(t=2.460,P=0.015)while left grip strength improved significantly in group C(t=
2.051,P=0.043)one year after intervention.In group D,muscular strength in both 12
month and 24-month did not change compared with baseline(both
P>0.05).Furthermore,serum procollagen type I N-terminal propeptide elevated
significantly in group A(t=-2.962,P=0.004),group B(t=-2.888,P=0.005),and group
C(t=-2.441,P=0.016),whereas beta-C-terminal telopeptide of type I collagen
decreased significantly in group B(t=2.285,P=0.024)and group
D(t=2.596,P=0.011)two years after intervention.Conclusion Enhanced exercise and
combined calcium vitamin D supplementation may help sustain muscle strength in
postmenopausal women,while calcium and vitamin D supplementation may improve
muscular strength within a short period of time.
PMID- 28695805
TI - Clinical Analysis of 77 Patients with Allergic Bronchopulmonary Aspergillosis in
Peking Union Medical College Hospital.
AB - Objective To summarize the clinical features of allergic bronchopulmonary
aspergillosis(ABPA)to facilitate its early diagnosis and treatment. Methods We
retrospectively analyzed the clinical data of 77 patients who had been admitted
to Peking Union Medical College Hospital from January 1996 to July 2015 with
ABPA. Results The average age of these 77 patients(38 men and 39 women)was(41.8+/
18.3)years. The co-morbidities included bronchial asthma(n=74,96%)and pulmonary
cystic fibrosis(n=3,4%). The main symptoms and signs of ABPA were chronic
cough(100%),sputum production(97%),wheeze(86%),sputum plugs(25%),blood-stained
sputum(18%),hemoptysis(9%),chest pain(9%),fever(47%),weight loss(30%),and night
sweat(12%). Laboratory tests revealed elevated levels of blood eosinophils
absolute count(87%),anti-aspergillus antigen-specific IgE(89%)and specific
IgG(57%)as well as a positive result of Aspergillus antigen skin test(88%).
Pulmonary function testing showed that the incidences of obstructive ventilation
and diffusion dysfunction were 66% and 65%,respectively;in
addition,bronchodilatation test showed positive result in 60% of the patients.
The most common CT findings were central bronchiectasis(81%),patchy
infiltrations(79%),pleural thickening(49%),mediastinal adenopathy(35%),nodular
opacities(25%),mucoid impaction(21%),and fleeting infiltrations(35%). In
addition,44 cases(58%)were misdiagnosed as tuberculosis,pneumonia,lung
abscess,and/or lung cancer autoimmune diseases. Conclusions ABPA can be easily
misdiagnosed. ABPA should be carefully considered in patients with asthma or
pulmonary cystic fibrosis who also suffer from wheeze,sputum plugs,elevated
eosinophils central bronchiectasis,and fleeting infiltrations.
PMID- 28695806
TI - Illness Attribution of Outpatients with Multiple Somatic Symptoms in Peking Union
Medical College Hospital.
AB - Objective To explore the characteristics of illness attribution of outpatients
with multiple somatic symptoms in Peking Union Medical College Hospital. Methods
It was a cross-sectional study conducted from March to October,2012. A total of
150 outpatients were recruited from the departments of
Gastroenterology,Traditional Chinese Medicine and Psychological Medicine by
convenience sampling. Somatic symptom scale of the Patient Health Questionnaire
(PHQ-15) was used to screening each patient in the waiting list. With the cut-off
value of 10,patients were divided into the somatic symptom positive (SOM+) group
and somatic symptom negative (SOM-) group. Sociodemographic characteristics were
compared between these two groups. All the subjects completed interviews
including questions about illness attribution. All the answers of illness
attribution were concluded into three major groups as physical
factors,situational factors and psychological factors. Results The proportion of
female was significantly higher in SOM+ group than in SOM-group (69.3% vs.
53.3%;chi2=4.048,P=0.044). In SOM+ group,significantly more patients contributed
their illness to psychological factors (64.0% vs. 45.0%;chi2=5.273,P=0.022).
There was no significantly difference between SOM+ group and SOM-group on the
phenomenon of multiple illness attribution (41.0% vs. 32.0%;chi2=1.407,P=0.236).
However,in the Department of Gastroenterology,there were significantly more
outpatients in SOM+ group with multiple illness attribution (60.0% vs.
32.0%;chi2=3.945,P=0.047).Conclusions The outpatients in general hospital with
multiple somatic symptoms are more likely to contribute their illness to
psychological factors. The phenomenon of multiple illness attribution is common
among patients. Clinicians should increase their awareness and knowledge of
illness attribution,so as to provide better holistic health services.
PMID- 28695807
TI - Effect of Transverse Position and Numbers on the Stability of the Spinal Pedicle
Screw Fixation during the Pedicle Cortex Perforation.
AB - Objective To evaluate the effect of transverse position and numbers on the
stability of the spinal pedicle screw fixation during the pedicle cortex
perforation. Methods The vertebral compression fracture was performed in the L1
vertebral body using the Chiba's method from 60 fresh thoracic and lumbar
vertebrae samples of sheep(T13-L3),which were randomly divided into 6
groups(A,B,C,D,E,and F)using a lottery method. Bilateral pedicles of vertebral
arch of T14 and L2 were inserted pedicle screws,connecting titanium rods to fix
T14-L2 segments. Then the samples of groups B,C,D,E,and F were removed a quarter
of right side of lateral T14 thoracic pedicle cortical,which were considered the
pedicle cortex perforation model. Finally,each group was fixed on different
numbers of crosslinks:group A(0 crosslink,Intact),group B(0 crosslink,NCL),group
C(1 crosslink,1/2 of the rods,MCL),group D(1 crosslink,1/3 of the rods close to
T14,PCL),group E(1 crosslink,2/3 of the rods away from T14,DCL)and group F(2
crosslinks,1/3 and 2/3 of the rods respectively,TCL). After all samples were
subject to 10 000 times of fatigue test with biomechanics test machines,the axial
compressive stiffness,range of the motion(ROM)of the 6
directions(flexion,extension,lateral bending,and axial rotation),and the maximum
pullout of the screws of the T14 pedicle cortex perforation were measured and
compared among these 6 groups. Results The axial compressive stiffness in groups
A,C,D,E,and F was significantly higher than that in group B(all P<0.05),and group
A was significantly higher than group F(P<0.05) . The maximum pullout in groups
A,C,D,E,and F were significantly higher than that in group B(all P<0.05),and
group A was significantly higher than group F and groups C,D,and E were
significantly lower than group F(all P<0.05). ROM of flexion,extension,lateral
bending,and axial rotation in groups A,B,C,D,E,and F were significantly lower
than that in group B(P=0.000),and ROM of left and right axial rotation in groups
C,D,and E were significantly higher than in that group F(P=0.000). Conclusions
During the pedicle cortex perforation,adding of one crosslink can improve the
stability of the pedicle cortex perforation,and adding of two crosslinks can
approximately achieve the same stability as the pedicle screw fixation with no
pedicle cortex perforation. The location of the crosslink has no obvious effect
on the short segment of spinal fixation.
PMID- 28695808
TI - Impact of Lymphocyte Subsets on Chemotherapy Efficacy and Long-term Survival of
Patients with Advanced Non-small-cell Lung Cancer.
AB - Objective To analyze the impact of lymphocyte subsets on chemotherapy efficacy
and long-term survival of patients with advanced non-small cell lung
cancer(NSCLC).Methods Totally 125 NSCLC patients who had received first-line
chemotherapy including paclitaxel and pemetrexed with/without platinum were
enrolled in this study.Lymphocytes from peripheral blood were collected before
and after two cycles of first-line chemotherapy.Flow cytometry was performed to
determine the expressions of 21 fluorescence-labeled lymphocyte subsets.Based on
the imaging findings,chemotherapy efficacy was evaluated,and impact of the
lymphocyte subsets on progression-free survival(PFS)and overall survival(OS)were
analyzed.Results The baseline peripheral lymphocyte subsets showed no significant
difference among groups receiving different treatment protocols(all P>0.05).After
2 cycles of chemotherapy,the percentage of CD4+CD29+lymphocytes was(16.87+/
5.28)% in progressive disease group,which was significantly lower than those in
complete remission+partial remission group [(22.42+/-7.88)%,P=0.013] and stable
disease group [(21.88+/-6.81)%,P=0.009].The median PFS was 7.07 months and median
OS was 23.00 months.Cox multivariable regression analysis showed that the
percentages of HLA-DR+(HR:1.03,95%CI:1.01-1.05,P<0.001) and CD3+HLA
DR+lymphocytes (HR:1.05,95%CI:1.01-1.08,P<0.001)were positively correlated with
OS.Conclusions The rise of CD4+CD29+T lymphocytes in patients after chemotherapy
indicates good chemotherapy efficacy.Higher percentage of HLA-DR+and CD3+HLA
DR+lymphocytes in peripheral blood before chemotherapy predicts favorable
prognosis.
PMID- 28695809
TI - Diagnosis and Clinical Analysis of Primary Thyroid Lymphoma.
AB - Objective To summarize our experiences in the diagnosis and prognosis of
different subtypes of primary thyroid lymphoma (PTL). Methods The clinical data
of 27 PTL patients who were treated in our hospital from January 1998 to December
2014 were retrospectively analyzed. The pathological types of these patients
included B cell lymphoma unclassifiable (BCLU) (n=5),mucosa-associated lymphiod
tissue lymphoma (MALT) (n=9),diffuse large B cell lymphoma (DLBCL) (n=12),and T
cell lymphoma (n=1). Results Of all these 27 cases,the most common clinical
symptom was painless swelling of the neck (n=21,77.8%). Of 7 patients who had
received preoperative fine needle biopsy,lymphoma was suspected in 2 cases
(28.6%). Among these 7 cases,the positive rate of suspicious lymphoma was 66.7%
in 3 DLBCL patients,0 in 3 MALT patients,and 0 in 1 BCLU paitent. Also,25
patients underwent intraoperative frozen pathological examination,which revealed
lymphoma or suspicious lymphoma in 16 cases (64.0%); in these patients,the
positive rate was 66.7% for BCLU,77.8% for MALT,58.3% for DLBCL,and 0 for T-cell
lymphomas. The overall survival was (89.3+/-12.4) months,and the overall 5-year
survival rate was 61.6%. The estimated survival in symptomatic group was 31.6
months,which was significantly shorter than that in asymptomatic group (97.9
months) (P=0.032). Other factors including age,sex,tumor size,tumor
stage,international prognostic index,tracheal compression,lactate
dehydrogenase,residual tumor,and pathological type showed no significant effect
on survival(all P>0.05). Conclusions DLBCL has the highest fine needle biopsy
positive rate,MALT has the highest frozen pathological positive rate,and
intraoperative frozen pathology has more malignant results than the preoperative
fine needle biopsy in the diagnosis. The accompanying lymphoma symptoms may be an
adverse prognostic factor.
PMID- 28695810
TI - Long-term Outcomes of cN0 Papillary Thyroid Carcinoma without Elective Central
Compartment Neck Dissection.
AB - Objective To determine the long-term outcomes of cN0 papillary thyroid carcinoma
without elective central compartment neck dissection. Methods The clinical data
of 180 patients with clinically lymph node negative papillary thyroid carcinoma
who were treated in our center between 2000 and 2005 were retrospectively
analyzed. All of these patients did not receive elective central compartment neck
dissection. Clinicopathological characteristics including gender,age,surgical
range,pathologic type,tumor size,and extrathyroidal extension(ETE)or not were
collected. Results After a median follow-up period of 90 months,only one patient
died of stroke without tumor. Sixteen patients had tumor recurrence:seven
patients had a recurrent disease in residual thyroid tissue,two in the thyroid
bed,six in central compartment,eight in lateral cervical compartment,and one in
lung. The 10-year overall survival,disease-specific survival,and recurrence-free
survival was 99.4%,100%,and 87.9%,respectively. The 10-year accumulative lymph
node recurrence rate in central compartment and lateral compartment was 7.8% and
7.0%,respectively. ETE was an independent risk factor for central compartment
lymph node recurrence. Male gender(P=0.010)and ETE(P=0.028)were independent risk
factors for lateral compartment lymph node recurrence. Conclusions The prognosis
of patients with cN0 papillary thyroid carcinoma without elective central
compartment neck dissection is good after ten years of follow-up. Male gender and
ETE are independent risk factors for lateral compartment lymph node recurrence.
PMID- 28695811
TI - Clinicopathological Features Analysis of 86 Endometrial Endometrioid
Adenocarcinoma Patients with Adnexal Involvement.
AB - OBJECTIVE: To investigate the clinicopathological features of endometrial
endometrioid adenocarcinoma(EEA)with adnexal involvement.Methods The
clinicopathological data of 86 EEA patients who underwent surgical treatment at
our center from January 2000 to December 2015 were analyzed retrospectively.The
clinicopathological features were compared between patients with occult adnexal
involvement and those with gross adnexal involvement.Results A total of 86 EEA
patients with adnexal involvement(mean age:58.1 years)were included in this
study,accounting for 5.4%(86/1592)of the EEA patients during the same
period.Among these 86 patients,there were 13 premenopausal
patients(15.1%)including 2 premenopausal patients aged under 40 years.Gross
adnexal involvement was found in 47 patients(54.7%),while occult adnexal
involvement was found in 39 patients(45.3%)in pathology evaluation.Ovarian
metastasis was found in 34 patients(39.5%),followed by both ovarian and tubal
metastasis in 19 patients(22.1%)and tubal metastasis in 33 patients(38.4%).The
expressionss of estrogen receptor(chi2=8.086,P=0.042)and progesterone
receptor(PR)(chi2=9.149,P=0.026)were significantly different between gross
adnexal involvement group and occult adnexal involvement group,whereas no
significant difference was found in other clinicopathological features(all
P>0.05).The non-conditional Logistic regression analysis showed that,compared
with PR no-expression group,the rate of occult microscopic adnexal involvement in
PR low-expression group was 6.375 times of that of the gross adnexal
involvement(P=0.005,95%CI:1.768-22.976),and the rate of occult microscopic
adnexal involvement in the PR high-expression group was 3.719 times of that of
gross adnexal involvement(P=0.048,95%CI:1.009-13.702). Conclusion PR expression
level is remarkably lower in EEA patients with gross adnexal involvement than
those with occult adenxal involvement.
PMID- 28695812
TI - Clinical and Sonographic Features of Mammary Paget's Disease.
AB - Objective To summarize the clinical and sonographic features of mammary Paget's
disease (MPD). Methods Totally 34 female patients with pathologically confirmed
MPD were retrospectively recruited. According to diagnosis,the clinical data and
sonographic findings were reviewed and analyzed. Results Among these 34
patients,7 patients had single MPD; in the remaining 27 patients,16 were
accompanied by invasive ductal carcinoma (IDC),7 by ductal carcinoma in situ
(DCIS),3 by both IDC and DCIS,and 1 by other pathologic types of carcinoma.
Twenty-four patients presented with typical clinical features of MPD,whereas 10
patients had no typical features of MPD. Among the 24 patients with typical
clinical features,ultrasound examinations showed that 11 had echoic abnormality
in nipple-areolar complex,14 had lesions of breast,and 14 had
microcalcifications. Among the 10 patients without typical clinical
features,ultrasound examinations revealed echoic abnormality in nipple-areolar
complex in 3 cases,breast lesions in 9 cases,and microcalcifications in 6 cases.
Among the 14 patients with echoic abnormality in nipple-areolar complex,all of
them presented as rich blood flow in nipple detected by color Doppler
ultrasonography. Conclusions The main clinical feature of MPD is abnormalities in
nipple-areolar complex. Sonography can recognize the echoic abnormalities of
nipple and lesions of breast. Sonographer should be careful of the nipple-areolar
complex when mass is found in breast.
PMID- 28695813
TI - Value of Acoustic Radiation Force Impulse Imaging in the Diagnosis of Early Non
alcoholic Steatohepatitis.
AB - Objective To evaluate the value of acoustic radiation force impulse(ARFI)imaging
in the diagnosis of early non-alcoholic steatohepatitis(NASH).Methods Totally 32
SD rats were randomly divided into high-fat diet group(n=24)and normal-diet
group(n=8)by using the random number table. At the end of the 4th,8th,12th,and
16th week,six rats from the high-diet group and two rats from the normal-diet
group were selected blindly for weighting,blood biochemical test,conventional
ultrasound,and ARFI imaing. HE staining was used for pathological observation.
Results None of the 32 rats developed liver fibrosis. Based on the pathological
results,these rats were divided into M1 [mild-to-moderate simple fatty
liver(SS)],M2(severe SS),M3(severe SS with early NASH),and C groups(normal
control). Early NASH was seen only in the severe hepatic steatosis groups,and its
distribution had a significant difference(P=0.006). The diagnostic accuracy of
conventional ultrasound based on histological results was 34.4%(11/32). The ARFI
value of M3 group was significantly lower than that of M2 group [(1.16+/-0.04)m/s
vs.(1.22+/-0.05)m/s;t=2.301,P=0.04),and the low-density lipoprotein of M3 group
was significantly higher than M2 group [(1.53+/-0.07)mmol/L vs.(1.21+/
0.22)mmol/L;t=3.075,P=0.01),while other clinical indicators had no statistical
difference between these two groups. Conclusions The development of early NASH is
associated with the severity of hepatic steatosis. ARFI value can provide
important information to identify early NASH in patients with severe hepatic
steatosis.
PMID- 28695814
TI - Effect of Different Sufentanil Concentration Regimens on Postoperative Pain
Control and Its Adverse Events in Intravenous Patient-controlled Analgesia.
AB - Objective To compare the analgesic effect and incidences of adverse events of
different sufentanil concentration regimens in postoperative intravenous patient
controlled analgesia(PCA).Methods We retrospectively analyzed the clinical data
of 6231 patients undergoing elective general anesthesia using sufentanil as
postoperative intravenous PCA regimen in Peking Union Medical College Hospital
from January 2004 to December 2016.These patients were subcategorized into 4
groups according to the sufentanil concentration regimens:0.4
MUg/ml(SF4,n=1421),0.6 MUg/ml(SF6,n=2489),0.8 MUg/ml(SF8,n=1326),and 1.0
MUg/ml(SF10,n=995).Total drug consumption within 48 h after surgery,analgesic
effect,and incidences of adverse events were compared among these four
groups.Results The cohort consisted of 2874 males(46.1%)and 3357 females(53.9%)in
the age group from 3 years to 91 years(median:52.5 years).The postoperative 48 h
sufentanil consumption was significantly different among these four groups in
terms of volume(chi2=87.316,P<0.001)and dosage(chi2=20.261,P<0.001).Meanwhile,the
VAS scores at rest and during activity on postoperative day 1(POD1)and POD2
showed no statistical significance among these four groups (both P>0.05).As for
the adverse events,the sedation score in POD1(chi2=9.042,P=0.029)and incidence of
no bowl movement on both POD1(chi2=7.855,P=0.012)and POD2(chi2=5.635,P=0.044)were
significantly different among groups,whereas the incidences of other adverse
events showed no significant difference(all P>0.05).Conclusion In patients using
intravenous sufentanil PCA as their postoperative analgesia regimen after general
anesthesia,regimens with higher sufentanil concentrations may result in more
adverse events such as sedation and no bowl movement without improving analgesic
outcomes.
PMID- 28695815
TI - Effectiveness of Underbody Forced-air Warming System in Preventing Hypothermia in
Patients Undergoing Major Surgeries.
AB - Objective To compare the effectiveness of the forced-air warming system and the
conventional warming care practice in preventing hypothermia in patients
undergoing major surgeries.Methods A total of 62 patients were enrolled in this
study. Patients of both sexes,aged>=18 years,and with an ASA physical status I
III were included and allocated randomly into intervention group(n=30)or control
group(n=32). Patients in the intervention group were provided forced-air
warming,either prior to induction or during the surgery procedure depending on
core temperature monitoring results. In the control group,patients were warmed
with conventional warming care without any intervention. Core temperature was
measured by Spot-On sensor and tympanic membrane thermometer,blood pressure,the
electrocardiogram,heart rate,pulse oxygen staturation,and partial pressure of end
tidal CO2 were also monitored continuously in the two
groups.Crystalloid,colloid,and allogeneic blood were also recorded by strict
protocol. Results Intraoperative hypothermia monitored with tympanic thermometer
was observed in 23 patients(71.87%)in the control group,which was significantly
higher than that (0) in the intervention group(P=0.00). In addition,the incidence
of hypothermia monitored by Spot-On sensor was 81.25%(n=26)in control group and
13.33%(n=4)in intervention group(P=0.00). Conclusion Compared with the
conventional warming care,forced-air warming system is more effective in
preventing hypothermia during major surgeries.
PMID- 28695816
TI - Research Advances in the Role of Bromodomain-containing Protein 4 in Epithelial
mesenchymal Transition in Asthma.
AB - Asthma is a chronic airway disease characterized by airway inflammation and
airway remodeling. Chronic airway inflammation can be involved in airway
remodeling in asthmatic patients by incuding epithelial-mesenchymal transition
(EMT).Bromodomain-containing protein 4 (BRD4) is a key transcriptional regulator
in mammals,and many evidences have shown that BRD4 plays a pivotal role in airway
remodeling via nuclear factor-kappaB/RelA signaling pathway. This review
summarizes the recent advances in the role of BRD4 in regulating EMT,with an
attempt to elucidate the molecular mechanisms of asthma and inform the prevention
and control of asthma.
PMID- 28695817
TI - Effects of Periodontal Ligament Cells on Alveolar Bone Metabolism under the
Action of Force and Inflammatory Factors and Its Molecular Mechanisms.
AB - Periodontal ligament may have independent response to orthodontic stimulation and
thus initiate alveolar bone osteogenesis and osteoclasts. Orthodontic-induced
alveolar bone remodeling has no bone loss,while inflammation can lead to alveolar
bone loss,suggesting that force signal and inflammatory factors may induce the
differentiation of undifferentiated cells in the periodontal ligament via
different pathways. The strength of the force and the nature of the force (basal
tension and fluid shear force) may affect the differentiation of periodontal
ligament cells,and may produce antagonistic or synergistic effect with the
inflammatory factors through complex autocrine and paracrine regulation,resulting
in local bone reconstruction,which is manifested as bone deposition and bone
absorption. Studies have shown that Wnt signaling is an important regulatory
pathway for osteoblast differentiation. Inflammatory factors can block the
differentiation of stem cells into osteoblasts. The Wnt pathway is closely
related to the effects of force and inflammatory factors on the differentiation
of periodontal ligament cells.
PMID- 28695818
TI - Progress in Molecular Genetic Study of Mitochondrial Cardiomyopathy.
AB - Mitochondria plays a key role in providing ATP for the energy-consuming cardiac
tissues. Mitochondrial cardiomyopathy is a myocardial condition characterized by
abnormal heart structure and/or function secondary to genetic defects involving
the mitochondrial respiratory chain. The typical cardiac manifestations of
mitochondrial cardiomyopathy include hypertrophic and dilated
cardiomyopathy,while left ventricular myocardial noncompaction is less common.
Recent research has suggested that most mitochondrial diseases result from
mitochondrial DNA mutation,which can be found in genes that encode ancillary
proteins needed for genetic transcription (tRNA),in genes that encode subunits of
the electron transport chain complexes,or in genes that control the activities of
the mitochondria called D-loop zone. However,the exact physiological mechanisms
remain unclear. This review summarizes the recent advances in the molecular
mechanism of mitochondrial cardiomyopathy.
PMID- 28695819
TI - Role of Ultrasound in the Management of Thyroid Nodules and Thyroid Cancer.
AB - The management of thyroid nodules can be classified into narrow-and broad-sense
levels. The broad-sense procedures are used for special population and include
screening,risk assessment of thyroid nodules,follow-up of benign thyroid
nodules,surgical operation,post-operative follow-up,and assessment and treatment
of recurrence and/or metastasis of thyroid cancer. The narrow-sense procedures
are for individual patients and the whole process includes the
assessment,supervision,treatment,and reassessment of thyroid lesion. Ultrasound
plays different roles at different management stages. With the development of
ultrasonic technology and improvement of diagnostic accuracy,ultrasound has
gradually becoming an irreplaceable imaging tool in the diagnosis of thyroid
nodules. In this article we review the history of thyroid ultrasound and the
latest international guidelines on the management of thyroid nodules and
differentiated thyroid cancer by focusing on the role of ultrasound throughout
the management of thyroid nodules.
PMID- 28695820
TI - Research Advances in Clinical and Imaging Characteristics of Intraductal
Papillary Mucinous Neoplasm of the Bile Duct.
AB - Understanding on the intraductal papillary mucinous neoplasm of the pancreas
(IPMN-P) has dramatically improved in the past three decades. A new disease named
intraductal papillary mucinous neoplasm of the bile duct (IPMN-B) reported in
recent years shares several similar clinical features with IPMN-P. The clinical
manifestations and imaging characteristics of IPMN-B have been gradually
recognized. This review summarizes some of the typical cases reported since 2000
and find that clinical manifestations of IPMN-B include epigastric
discomfort,biliary colic,jaundice,intermittent fever,sometimes without any
symptoms; imaging triads for IPMN-B are mucobilia,dilated bile duct,and bile duct
mural nodule.
PMID- 28695821
TI - An outbreak of locally acquired Plasmodium vivax malaria among migrant workers in
Oman.
AB - Plasmodium vivax is the most widely distributed human malaria parasite. Outside
sub-Saharan Africa, the proportion of P. vivax malaria is rising. A major cause
for concern is the re-emergence of Plasmodium vivax in malaria-free areas. Oman,
situated in the south-eastern corner of the Arabian Peninsula, has long been an
area of vivax malaria transmission but no locally acquired cases were reported in
2004. However, local transmission has been registered in small outbreaks since
2007. In this study, a local outbreak of 54 cases over 50 days in 2014 was
analyzed retrospectively and stained blood slides have been obtained for parasite
identification and genotyping. The aim of this study was to identify the
geographical origin of these cases, in an attempt to differentiate between
imported cases and local transmission. Using circumsporozoite protein (csp),
merozoite surface protein 1 (msp1), and merozoite surface protein 3 (msp3)
markers for genotyping of parasite DNA obtained by scrapping off the surface of
smears, genetic diversity and phylogenetic analysis were performed. The study
found that the samples had very low genetic diversity, a temperate genotype, and
a high genetic distance, with most of the reference strains coming from endemic
countries. We conclude that a small outbreak of imported malaria is not
associated with re-emergence of malaria transmission in Oman, as no new cases
have been seen since the outbreak ended.
PMID- 28695822
TI - Arid1b haploinsufficient mice reveal neuropsychiatric phenotypes and reversible
causes of growth impairment.
AB - Sequencing studies have implicated haploinsufficiency of ARID1B, a SWI/SNF
chromatin-remodeling subunit, in short stature (Yu et al., 2015), autism spectrum
disorder (O'Roak et al., 2012), intellectual disability (Deciphering
Developmental Disorders Study, 2015), and corpus callosum agenesis (Halgren et
al., 2012). In addition, ARID1B is the most common cause of Coffin-Siris
syndrome, a developmental delay syndrome characterized by some of the above
abnormalities (Santen et al., 2012; Tsurusaki et al., 2012; Wieczorek et al.,
2013). We generated Arid1b heterozygous mice, which showed social behavior
impairment, altered vocalization, anxiety-like behavior, neuroanatomical
abnormalities, and growth impairment. In the brain, Arid1b haploinsufficiency
resulted in changes in the expression of SWI/SNF-regulated genes implicated in
neuropsychiatric disorders. A focus on reversible mechanisms identified Insulin
like growth factor (IGF1) deficiency with inadequate compensation by Growth
hormone-releasing hormone (GHRH) and Growth hormone (GH), underappreciated
findings in ARID1B patients. Therapeutically, GH supplementation was able to
correct growth retardation and muscle weakness. This model functionally validates
the involvement of ARID1B in human disorders, and allows mechanistic dissection
of neurodevelopmental diseases linked to chromatin-remodeling.
PMID- 28695823
TI - Pervasive epigenetic effects of Drosophila euchromatic transposable elements
impact their evolution.
AB - Transposable elements (TEs) are widespread genomic parasites, and their evolution
has remained a critical question in evolutionary genomics. Here, we study the
relatively unexplored epigenetic impacts of TEs and provide the first genome-wide
quantification of such effects in D. melanogaster and D. simulans. Surprisingly,
the spread of repressive epigenetic marks (histone H3K9me2) to nearby DNA occurs
at >50% of euchromatic TEs, and can extend up to 20 kb. This results in
differential epigenetic states of genic alleles and, in turn, selection against
TEs. Interestingly, the lower TE content in D. simulans compared to D.
melanogaster correlates with stronger epigenetic effects of TEs and higher levels
of host genetic factors known to promote epigenetic silencing. Our study
demonstrates that the epigenetic effects of euchromatic TEs, and host genetic
factors modulating such effects, play a critical role in the evolution of TEs
both within and between species.
PMID- 28695824
TI - A multi-scale model for hair follicles reveals heterogeneous domains driving
rapid spatiotemporal hair growth patterning.
AB - The control principles behind robust cyclic regeneration of hair follicles (HFs)
remain unclear. Using multi-scale modeling, we show that coupling inhibitors and
activators with physical growth of HFs is sufficient to drive periodicity and
excitability of hair regeneration. Model simulations and experimental data reveal
that mouse skin behaves as a heterogeneous regenerative field, composed of
anatomical domains where HFs have distinct cycling dynamics. Interactions between
fast-cycling chin and ventral HFs and slow-cycling dorsal HFs produce bilaterally
symmetric patterns. Ear skin behaves as a hyper-refractory domain with HFs in
extended rest phase. Such hyper-refractivity relates to high levels of BMP
ligands and WNT antagonists, in part expressed by ear-specific cartilage and
muscle. Hair growth stops at the boundaries with hyper-refractory ears and
anatomically discontinuous eyelids, generating wave-breaking effects. We posit
that similar mechanisms for coupled regeneration with dominant activator, hyper
refractory, and wave-breaker regions can operate in other actively renewing
organs.
PMID- 28695825
TI - Tsc2 disruption in mesenchymal progenitors results in tumors with vascular
anomalies overexpressing Lgals3.
AB - Increased mTORC1 signaling from TSC1/TSC2 inactivation is found in cancer and
causes tuberous sclerosis complex (TSC). The role of mesenchymal-derived cells in
TSC tumorigenesis was investigated through disruption of Tsc2 in craniofacial and
limb bud mesenchymal progenitors. Tsc2cKOPrrx1-cre mice had shortened lifespans
and extensive hamartomas containing abnormal tortuous, dilated vessels prominent
in the forelimbs. Abnormalities were blocked by the mTORC1 inhibitor sirolimus. A
Tsc2/mTORC1 expression signature identified in Tsc2-deficient fibroblasts was
also increased in bladder cancers with TSC1/TSC2 mutations in the TCGA database.
Signature component Lgals3 encoding galectin-3 was increased in Tsc2-deficient
cells and serum of Tsc2cKOPrrx1-cre mice. Galectin-3 was increased in TSC-related
skin tumors, angiomyolipomas, and lymphangioleiomyomatosis with serum levels in
patients with lymphangioleiomyomatosis correlating with impaired lung function
and angiomyolipoma presence. Our results demonstrate Tsc2-deficient mesenchymal
progenitors cause aberrant morphogenic signals, and identify an expression
signature including Lgals3 relevant for human disease of TSC1/TSC2 inactivation
and mTORC1 hyperactivity.
PMID- 28695826
TI - An insect anti-antiaphrodisiac.
AB - Passive mechanisms of mate guarding are used by males to promote sperm precedence
with little cost, but these tactics can be disadvantageous for their mates and
other males. Mated females of the plant bug Lygus hesperus are rendered
temporarily unattractive by seminal fluids containing myristyl acetate and
geranylgeranyl acetate. These antiaphrodisiac pheromones are gradually released
from the female's gonopore, declining until they no longer suppress male
courtship. Because starting quantities of these compounds can vary widely, the
repellant signal becomes less reliable over time. Evidence was found of a
complimentary mechanism that more accurately conveys female mating status. Once
inside the female, geranylgeranyl acetate is progressively converted to
geranylgeraniol then externalized. Geranylgeraniol counteracts the
antiaphrodisiac effect despite having no inherent attractant properties of its
own. This is the first evidence for such an anti-antiaphrodisiac pheromone,
adding a new element to the communication mechanisms regulating reproductive
behaviors.
PMID- 28695827
TI - Experimental Toxoplasmosis in Japanese Quails (Coturnix coturnix japonica).
AB - OBJECTIVE: In this study, forming of experimental toxoplasmosis in quails;
clinical, pathological, and serological determination of tissue lesions and
bioassay techniques, which were aimed to compare them and determine pathogenesis.
METHODS: A total of 120 one-year-old female quails (Coturnix coturnix japonica)
were divided into oral infection, parenteral infection, and control groups. The
oral group was infected with 0.5 ml inoculum suspension containing 106
tachyzoites of Toxoplasma gondii, whereas the control group was administered 0.5
ml of saline. The parenteral group was further divided into the following four
subgroups: intraperitoneal, intramuscular, intravenous, and cloacal. The quails
of the parenteral group were also divided into two groups and one by control
group within itself for the 105 and 104 doses of the tachyzoite inoculums.
RESULTS: Because of acute toxoplasmosis, death occurred in a quail that as
intramuscularly infected with 105 tachyzoites; the quail exhibited neurological
clinical symptoms such as torticollis, ataxia, and tremor. In histopathologic
examination, T. gondii tissue cysts were detected in infected quails that were
intramuscularly infected with 105 tachyzoites. Mouse trials were conducted using
tissues of seropositive quails and isolated from peritoneal fluids infected mice.
By Sabin-Feldman dye test and indirect hemagglutination test, seropositivity was
observed in quails infected with 105 and 104 tachyzoites. CONCLUSION: Similar
studies and subclinical cases, which may overlooked was concluded for diagnosis
of toxoplasmosis with useful bioassay applications and serological tests.
PMID- 28695828
TI - Prevalence of Haemoproteus spp. in Tumbler Pigeons (Columba livia domestica) in
Kirikkale Province, Turkey.
AB - OBJECTIVE: Haemoproteus spp. are common blood parasites of pigeons. They have
been reported in pigeons in many regions worldwide, including Turkey. Pigeon
breeding is a popular hobby in Kirikkale province, and there is no information
about the prevalence of Haemoproteus spp. The present study aimed to determine
the prevalence of Haemoproteus spp. in tumbler pigeons in Kirikkale province
(Kirikkale and Yahsihan district). METHODS: Blood samples were taken from the
wing vein of pigeons (n: 173) through microcapillary (with/heparin) tubes between
February and March 2016. Blood smears were stained with 5% Giemsa solution.
Ectoparasites of the pigeons were collected in separate sealed boxes.
Epidemiological data of the sampled pigeons (age and sex) were obtained from the
breeders. RESULTS: In total, 23 (%13.2) of 173 pigeons were infected with
Haemoproteus spp. Parasite was detected in 73.9% of pigeons over 1 year old and
26.1% of pigeon under 1 year age. Haemoproteus spp. was observed in 56.2% of
females (13/23) and 43.4% of males (10/23), Sex-related differences were not
observed (p = 0.821). Ectoparasites of the pigeons were identified as Columbicola
spp. CONCLUSION: To the best of our knowledge, this is the first study in
Kirikkale province that reported the prevalence of Haemoproteus spp. in pigeons.
PMID- 28695829
TI - Does the Intestinal Parasite Enterobius vermicularis Cause Acute Appendicitis?
AB - OBJECTIVE: Although intestinal parasitic infections rarely cause acute
appendicitis, they are common public health problems in undeveloped and
developing countries. Parasitic infections should be kept in mind in patients
clinically suspected of having acute appendicitis, and treatment procedures
should be adopted according to the etiology. METHODS: Herein we presented the
cases of four patients with clinical findings of acute appendicitis. Patients
were clinically suspected of having acute appendicitis, and Enterobius
vermicularis was detected in the pathological examinations of specimens. Pinworm
infections are common parasitic infections that may mimic appendicitis. RESULTS:
The pathology of the four cases was noted when the file of 186 patients aged
between 4 and 72 years who underwent surgery for acute appendicitis in my
hospital was retrospectively reviewed. When the appendectomy specimen was
examined histopathologically it was understood that acute appendicitis was caused
by Enterobius vermicularis parasite. CONCLUSION: In Enterobius infections,
performing systemic therapy for patients and their family members is sufficient.
To prevent unnecessary appendectomy, this type of infection should be made to ask
in the history and clinical findings of patients.
PMID- 28695830
TI - Prevalence and Density of Demodex folliculorum and Demodex brevis (Acari:
Demodicidae) in Erzincan Province.
AB - OBJECTIVE: This study aimed to determine the prevalence and density of Demodex
folliculorum and D. brevis in Erzincan Province and the association between
Demodex spp. and skin moisture, pH, and temperature. METHODS: The study included
total 300 healthy participants without dermatological ailments and residing in
Erzincan Province. Moisture, pH, and temperature of the cheek were measured, and
the presence of mite was determined in samples from the cheek, nasolabial, and
chin region using the standard superficial skin biopsy technique. RESULTS: The
prevalence and density of D. folliculorum and D. brevis were found to be 61.3%
(mean 14.3/cm2) and 23.3% (mean 3.2/cm2), respectively, in healthy participants.
Infestation by Demodex spp. was greater in the cheek (mean 10.4/cm2), followed by
the nasolabial region (mean 7.2/cm2) and chin (mean 6.6/cm2), respectively
(p<0.001). The prevalence and density of Demodex spp. were greater in those with
dry skin (mean 11.6/cm2), pH of 5.5-7.0 (mean 11.2/cm2), and temperature of 20-23
degrees C (mean 13.1/cm2). Males, with aged >60 years, with lower educational
status, and who were single were significantly more infested with Demodex spp.
CONCLUSION: Demodex mites are very prevalent in healthy individuals with
different skin moisture, skin pH, skin temperature, and demographic
characteristics. This may be taken into consideration when epidemiological and
clinical studies are conducted on patients having different dermatological
ailments.
PMID- 28695831
TI - Demodex Species Infestation in Patients with Ear Itching and Its Relationship to
Itch Severity.
AB - OBJECTIVE: The aim of the present study was to investigate Demodex species
infestation in patients with ear itching. The relationship between the severity
of ear itching and Demodex spp. positivity has not been previously reported in
the literature, and we believe that our study will make a significant
contribution to the understanding of the etiology of ear itching. METHODS: Fifty
patients with itching ears and 54 healthy control patients were asked to use a
visual analogue scale (VAS) to rate the itch, the itching period, and the
medication used for the itching. All samples were evaluated for Demodex spp.
under a light microscope. RESULTS: There was no statistically significant
difference between the groups in terms of numbers of Demodex spp. (p=0.154), and
there was no statistically significant difference between the groups in terms of
Demodex spp. positivity (p=0.054). Despite the lack of statistically significant
differences, Demodex spp. infestations were more common in the affected group
than in the control group. A positive and strongly significant relationship was
observed between the number of Demodex spp. and severity of ear itch in the
patient group based on VAS scores (p=0.0001; r=0.724). CONCLUSION: We found that
an increased number of Demodex spp. was strongly related to increased severity of
ear itching.
PMID- 28695832
TI - The Investigation of the Presence of Mites in Some Served Dry Foodstuffs.
AB - OBJECTIVE: Mites are microscopic organisms that lower the quality of life of
people who are sensitive to them by causing conditions such as atopic dermatitis,
allergic rhinitis, and asthma. These organisms are found in every habitat where
humans live. This study was conducted to determine the presence of storage mites
in dry food items. METHODS: Various food items were procured 10 times each in 300
gram samples. Mites were extracted with a Berlese funnel apparatus over
Erlenmeyer flasks containing 70% alcohol placed at the end of the funnel stems
for over 48 h. RESULTS: Of 25 food items examined in the study, only six were
contaminated by mites. Species of the mites found were Acarus siro (34.6%),
Glycyphagus domesticus (22.8%), Tyrophagus putrescentiae (16.8%), Tyrophagus spp.
(7.9%), Rhizoglyphus spp. (1%), Lepidoglyphus destructor (7.9%), Cheylettus
malacensis (4%), and Cheylettus spp. (2%). CONCLUSION: Although the results of
the study show that the presence of mites in food items sold in open containers
at open-air markets or stores was low, we suppose that they can cause important
health problems for sensitive people.
PMID- 28695833
TI - Investigation on the Collection and Economy of Medicinal Leeches from Wetlands
Around Lake Egirdir, Turkey.
AB - OBJECTIVE: This study aimed to investigate the collection and economy of
medicinal leeches from wetlands around Lake Egirdir, Turkey. METHODS: Data used
in this study were based on findings, observations, and face-to-face interviews
obtained from a research performed between January 2013 - February 2016 on
medicinal leech populations. RESULTS: The leech collecting is carried out without
any permission, by both local peoples and others especially who are from
Afyonkarahisar. This causes legal problems among leech collectors. Leech
collecting is not done as main job. Using small leeches (<1.5 g) that have not
reached a mature size for medicinal purposes impacts the collected leech size and
their market price. Leeches are sold for 40-1000 TL/kg (1 TL=0.25 ?) according to
season, product abundance, demand intensity, and leech size. Because of leech
collecting is carried out without under an economic organization, there is no
effect of leech collectors at determining the sale price of leeches. According to
the catchable stock size, the export potential of medicinal leeches is
approximately 1,200,000 ? from wetlands around Lake Egirdir. CONCLUSION: The
rational management of medicinal leech populations, socioeconomic benefits,
sustainable products, and ecological balance will be provided by operating
wetlands around Lake Egirdir according to stock estimation studies at regular
intervals and by evaluating effective marketing options under a cooperative.
PMID- 28695834
TI - Sand Flies and Their Control Methods.
AB - The main aim of managing arthropod vectors that carry the disease agents is
interrupting the infection cycle. Therefore, the management of the disease
implies that all precautions related to all elements (i.e., human, arthropod
vector, and reservoir) in the infection cycle need to be taken. There are
important points that need to be considered while dealing with sand flies
(Diptera: Psychodidae: Phlebotominae), which in many regions worldwide,
particularly in tropical and subtropical areas, are vectors of diseases such as
leishmaniasis and sand fly fever and are the arthropods of the infection cycle.
Because the larval control of the sand flies is very difficult and almost
impossible, the management is mainly conducted for the adults. The most effective
strategy for reducing both sand fly fever and leishmaniasis is managing sand
flies, particularly in areas where humans are located. In this review, the
morphology, biology, and taxonomy of sand flies; the integrated fighting and
management methods such as insecticide-impregnated bed nets and use of curtains,
zooprophylaxis, indoor and outdoor residual applications, larvicides, repellents,
and insecticide-impregnated dog collars; and data regarding many issues such as
insecticide resistance in sand flies have been emphasized on in the review.
PMID- 28695835
TI - The Concept of Travel Medicine and the Actual Situation of Travel-Related
Illnesses.
AB - Travel medicine defines all diseases and medical situations that are related to
travel. Travel medicine comprises infectious diseases, traumas, altitude
sickness, sun burns, embolisms, jet lag, and many more travel-related situations.
With the increasing possibility and ease of travel, the number of people who have
travelled internationally has exceeded 1.13 billion in 2014, and the revenues of
international travel have exceeded 1.25 trillion dollars. With every passing day,
international travels are shifting toward the developing countries and to more
exotic regions of the world, and travelers tend to be more adventurous and
daring, thereby increasing risky behaviors during travels. Traveling plays an
important role in transmitting infections such as Zika virus infection, Ebola,
avian flu, severe acute respiratory syndrome, Chikungunya, and dengue fever and
is the principal reason for the epidemics of these types of infections on a
global scale. With this background, we suggest that travel medicine is an
important but "neglected" medical discipline as the discipline of Parasitology
itself like most parasitic diseases.
PMID- 28695836
TI - A Case Series of Imported Malaria Caused by Plasmodium falciparum in Kayseri and
Review of Literature.
AB - Malaria is a major worldwide public health problem. In the last years, no
domestic cases of malaria have been detected and cases of imported malaria exist
only in Turkey. In this study, clinical and laboratory findings of five
Plasmodium falciparum (P. falciparum) malaria patients who were admitted to the
emergency department between January 2013 and December 2015 were retrospectively
presented. One of the patients was an African student, and the other patients had
a history of travelling to Africa. Ring formation was observed when Giemsa
staining was performed on the blood smears of all patients, and in three
patients, P. falciparum was also detected using multiplex polymerase chain
reaction (PCR) (Bio-Rad, United States of America). P. falciparum was not
detected by PCR in the other two patients. Malaria should be primarily considered
in febrile patients who have a history of travelling to endemic regions, and
peripheral blood smears should definitely be examined.
PMID- 28695837
TI - A Case of Cerebral Malaria Managed by Erythrocyte Exchange.
AB - Plasmodium falciparum may cause serious and sometimes even fatal cerebral
malaria. Cerebral malaria is a disease characterized by alterations in
consciousness and epileptic attacks; therefore, it requires a rapid evaluation
and quick intervention. It may progress to a fatal outcome despite administering
targeted therapeutic interventions. There are studies indicating that erythrocyte
exchange (erythrocytapheresis) can be a treatment modality for managing severe
malaria patients. In this case report, the successful management of a cerebral
malaria patient by the combination of antimalarial drug therapy and erythrocyte
exchange is presented.
PMID- 28695838
TI - Ruptured Pulmonary Cystic Echinococcosis Mimicking Tuberculosis in Childhood: A
Case Report.
AB - Cystic echinococcosis (CE) is a zoonotic disease; in places such as Turkey where
livestock is common, it is an endemic health concern. The most commonly involved
organ is the lungs in children. Pulmonary cysts can be asymptomatic; in some
cases, they may rupture and become symptomatic. Ruptured lung hydatid cysts may
often be confused with tuberculosis (Tbc) radiologically and clinically. . In
this report, we present an 8-year-old female patient admitted with cough, fever,
and sputum persisting since 2 weeks; her chest radiography and computed
tomography (CT) findings initially indicated Tbc, but the follow-up surgery led
to a diagnosis of ruptured lung CE. We want to emphasize that in children
belonging to places where livestock is common, if respiratory symptoms are
observed, CE and tuberculosis must be considered in the differential diagnosis,
and the final diagnosis should be supported by other microbiological-serological
tests.
PMID- 28695839
TI - Rapid prototyping of flexible intrafascicular electrode arrays by picosecond
laser structuring.
AB - OBJECTIVE: Interfacing the peripheral nervous system can be performed with a
large variety of electrode arrays. However, stimulating and recording a nerve
while having a reasonable amount of channels limits the number of available
systems. Translational research towards human clinical trial requires device
safety and biocompatibility but would benefit from design flexibility in the
development process to individualize probes. APPROACH: We selected established
medical grade implant materials like precious metals and Parylene C to develop a
rapid prototyping process for novel intrafascicular electrode arrays using a
picosecond laser structuring. A design for a rodent animal model was developed in
conjunction with an intrafascicular implantation strategy. Electrode
characterization and optimization was performed first in saline solution in vitro
before performance and biocompatibility were validated in sciatic nerves of rats
in chronic implantation. MAIN RESULTS: The novel fabrication process proved to be
suitable for prototyping and building intrafascicular electrode arrays.
Electrochemical properties of the electrode sites were enhanced and tested for
long-term stability. Chronic implantation in the sciatic nerve of rats showed
good biocompatibility, selectivity and stable stimulation thresholds.
SIGNIFICANCE: Established medical grade materials can be used for intrafascicular
nerve electrode arrays when laser structuring defines structure size in the micro
scale. Design flexibility reduces re-design cycle time and material certificates
are beneficial support for safety studies on the way to clinical trials.
PMID- 28695840
TI - Negative-charge-functionalized carbon nanodot: a low-cost smart cold emitter.
AB - Cold emission properties of carbon nanodots (CNDs) evaluated using ANSYS Maxwell
software are predicted to be size-dependent and then verified experimentally. In
order to correlate the electron emission properties with the size of CNDs, the
work function values were determined using ultraviolet photoelectron
spectroscopy. This is the first report on theoretical calculations based on
density functional theory and experimental results that confirm the work function
dependency on the charge state of the functional group attached on the particle
surface. The smallest CND (2.5 nm) has the highest percentage of negatively
charged groups as well as the lowest work function (5.18 eV). The smallest
dimension with the lowest work function assures that this sample is the best
suited for field emission. It shows excellent field emission properties with a
high current density of ~1.45 mA cm-2 at 2 V MUm-1 electric field, turn-on field
as low as 0.04 V MUm-1, very high field enhancement factor of 2.7 * 105 and high
stability. Overall, the zero-dimensional CNDs showed superior field emission
activity as compared to the higher dimensional carbon nanomaterials.
PMID- 28695841
TI - On the density of states of circular graphene quantum dots.
AB - We suggest a simple approach to calculate the local density of states that
effectively applies to any structure created by an axially symmetric potential on
a continuous graphene sheet such as circular graphene quantum dots or rings.
Calculations performed for the graphene quantum dot studied in a recent scanning
tunneling microscopy measurement (Gutierrez et al 2016 Nat. Phys. 12 1069-75)
show an excellent experimental-theoretical agreement.
PMID- 28695842
TI - Revealing correlation effect of Co 3d electrons in La3Co4Sn13 and Ce3Co4Sn13 by
infrared spectroscopy study.
AB - We report resistivity, specific heat and optical spectroscopy measurements on
single crystal samples of [Formula: see text] [Formula: see text] [Formula: see
text] and [Formula: see text] [Formula: see text] [Formula: see text]. We
observed clear temperature-induced spectral weight suppression below 4000
[Formula: see text] for both compounds in the conductivity spectra [Formula: see
text], indicating the progressive formation of gap-like features with decreasing
temperature. The suppressed spectral weight transfers mostly to the higher energy
region. This observation reflects the presence of the correlation effect in the
compounds. We attribute the correlation effect to the Co 3d electrons.
PMID- 28695843
TI - Magnetic impurity doping induced spin-glass state and short-range zigzag order in
the honeycomb iridate Na2IrO3.
AB - Based on the modified Heisenberg-Kitaev model, the effects of magnetic
substitution on the magnetic properties of the honeycomb-lattice iridate
[Formula: see text] [Formula: see text] are studied using Monte Carlo
simulations. It is observed that the long-range zigzag state of the original
system is rather fragile and can be replaced by a spin-glass state even for small
substitution, well consistent with the experimental observation in Ru-substituted
samples (Mehlawat et al 2015 Phys. Rev. B 92 134412). Both the disordered
Heisenberg and Kitaev interactions caused by the magnetic ion-doping are
suggested to be responsible for the magnetic phase transitions in the system.
More interestingly, a short-range zigzag order is suggested to survive above the
freezing temperature even at high magnetic impurity doping levels.
PMID- 28695844
TI - The structure of a complex of the lactonohydrolase zearalenone hydrolase with the
hydrolysis product of zearalenone at 1.60 A resolution.
AB - Zearalenone hydrolase (ZHD) is an alpha/beta-hydrolase that detoxifies and
degrades the lactone zearalenone (ZEN), a naturally occurring oestrogenic
mycotoxin that contaminates crops. Several apoenzyme and enzyme-substrate complex
structures have been reported in the resolution range 2.4-2.6 A. However, the
properties and mechanism of this enzyme are not yet fully understood. Here, a
1.60 A resolution structure of a ZHD-product complex is reported which was
determined from a C-terminally His6-tagged ZHD crystal soaked with 2 mM ZEN for
30 min. It shows that after the lactone-bond cleavage, the phenol-ring region
moves closer to residues Leu132, Tyr187 and Pro188, while the lactone-ring region
barely moves. Comparisons of the ZHD-substrate and ZHD-product structures show
that the hydrophilic interactions change, especially Trp183 NE1, which shifts
from contacting O2 to O12', suggesting that Trp183 is responsible for the
unidirectional translational movement of the phenol ring. This structure provides
information on the final stage of the catalytic mechanism of zearalenone
hydrolysis.
PMID- 28695845
TI - Recombinant ACHT1 from Arabidopsis thaliana: crystallization and X-ray
crystallographic analysis.
AB - Thioredoxins (Trxs) play important roles in chloroplasts by linking
photosynthetic light reactions to a series of plastid functions. They execute
their function by regulating the oxidation and reduction of disulfide bonds.
ACHT1 (atypical cysteine/histidine-rich Trx1) is a thylakoid-associated
thioredoxin-type protein found in the Arabidopsis thaliana chloroplast.
Recombinant ACHT1 protein was overexpressed in Escherichia coli, purified and
crystallized by the vapour-diffusion method. The crystal diffracted to 1.7 A
resolution and a complete X-ray data set was collected. Preliminary
crystallographic analysis suggested that the crystals belonged to space group
C2221, with unit-cell parameters a = 102.7, b = 100.6, c = 92.8 A.
PMID- 28695846
TI - Crystal structure of a beta-aminopeptidase from an Australian Burkholderia sp.
AB - beta-Aminopeptidases are a unique group of enzymes that have the unusual
capability to hydrolyze N-terminal beta-amino acids from synthetic beta-peptides.
beta-Peptides can form secondary structures mimicking alpha-peptide-like
structures that are resistant to degradation by most known proteases and
peptidases. These characteristics of beta-peptides give them great potential as
peptidomimetics. Here, the X-ray crystal structure of BcA5-BapA, a beta
aminopeptidase from a Gram-negative Burkholderia sp. that was isolated from
activated sludge from a wastewater-treatment plant in Australia, is reported. The
crystal structure of BcA5-BapA was determined to a resolution of 2.0 A and showed
a tetrameric assembly typical of the beta-aminopeptidases. Each monomer consists
of an alpha-subunit (residues 1-238) and a beta-subunit (residues 239-367).
Comparison of the structure of BcA5-BapA with those of other known beta
aminopeptidases shows a highly conserved structure and suggests a similar
proteolytic mechanism of action.
PMID- 28695847
TI - DNA-binding domain of myelin-gene regulatory factor: purification,
crystallization and X-ray analysis.
AB - The myelin sheath, which envelops axons in the vertebrate central nervous system,
is crucial for the rapid conduction of action potentials. Myelin-gene regulatory
factor (MRF) is a recently identified transcription factor that is required for
myelin-sheath formation. Loss of MRF leads to demyelinating diseases and motor
learning deficiency. MRF is a membrane-bound transcription factor that undergoes
autocleavage from the endoplasmic reticulum membrane. The N-terminus of MRF
contains a DNA-binding domain (DBD) that functions as a homotrimer. In this
study, the MRF DBD was cloned, purified and crystallized in order to understand
the molecular mechanism that regulates the transcription of myelin genes.
Selenomethionine was subsequently introduced into the crystals to obtain the
phases for the MRF DBD structure. The native and selenomethionine-labelled
crystals exhibited diffraction to 2.50 and 2.51 A resolution, respectively. The
crystals belonged to space group P321 and the selenomethionine-labelled crystals
had unit-cell parameters a = 104.0, b = 104.0, c = 46.7 A, alpha = 90, beta = 90,
gamma = 120 degrees . The calculated Matthews coefficient was 3.04 A3 Da-1 and
the solvent content was 59.5%, indicating the presence of one MRF DBD molecule in
the asymmetric unit.
PMID- 28695848
TI - Crystal structure of a family 6 cellobiohydrolase from the basidiomycete
Phanerochaete chrysosporium.
AB - Cellobiohydrolases belonging to glycoside hydrolase family 6 (CBH II, Cel6A) play
key roles in the hydrolysis of crystalline cellulose. CBH II from the white-rot
fungus Phanerochaete chrysosporium (PcCel6A) consists of a catalytic domain (CD)
and a carbohydrate-binding module connected by a linker peptide, like other known
fungal cellobiohydrolases. In the present study, the CD of PcCel6A was
crystallized without ligands, and p-nitrophenyl beta-D-cellotrioside (pNPG3) was
soaked into the crystals. The determined structures of the ligand-free and pNPG3
soaked crystals revealed that binding of cellobiose at substrate subsites +1 and
+2 induces a conformational change of the N-terminal and C-terminal loops,
switching the tunnel-shaped active site from the open to the closed form.
PMID- 28695849
TI - Full-length nisin immunity protein NisI from Lactococcus lactis in a lipid-free
form: crystallization and X-ray analysis.
AB - NisI is a lantibiotic-binding lipoprotein that is specific for nisin. Nisin
producing microorganisms use NisI as an immunity protein for self-protection
against nisin. Here, the purification, crystallization and preliminary X-ray
diffraction of full-length NisI from Lactobacillus lactis in a lipid-free form
(NisI22-C) are reported. Importantly, reductive methylation of the lysine
residues in NisI22-C was essential for initial crystallization. Only methylated
NisI22-C crystallized. The optimized crystals of methylated NisI22-C were grown
in 30-40 mM ammonium sulfate, 0.1 M sodium acetate pH 4.6, 16-18% PEG 4000 at 295
K and diffracted to 1.9 A resolution. The crystal belonged to space group
P212121, with unit-cell parameters a = 45.99, b = 76.67, c = 76.39 A, alpha =
beta = gamma = 90.0 degrees . Assuming the presence of one molecule in the
asymmetric unit, the estimated Matthews coefficient (VM) is 2.58 A3 Da-1 and the
estimated solvent content is 52.3%.
PMID- 28695850
TI - Assembly of Francisella novicida Cpf1 endonuclease in complex with guide RNA and
target DNA.
AB - Bacteria and archaea use the CRISPR-Cas system as an adaptive response against
infection by foreign nucleic acids. Owing to its remarkable flexibility, this
mechanism has been harnessed and adopted as a powerful tool for genome editing.
The CRISPR-Cas system includes two classes that are subdivided into six types and
19 subtypes according to conservation of the cas gene and loci organization.
Recently, a new protein with endonuclease activity belonging to class 2 type V
has been identified. This endonuclease, termed Cpf1, in complex with a single
CRISPR RNA (crRNA) is able to recognize and cleave a target DNA preceded by a 5'
TTN-3' protospacer-adjacent motif (PAM) complementary to the RNA guide. To obtain
structural insight into the inner workings of Cpf1, the crystallization of an
active complex containing the full extent of the crRNA and a 31-nucleotide dsDNA
target was attempted. The gene encoding Cpf1 from Francisella novicida was
cloned, overexpressed and purified. The crRNA was transcribed and purified in
vitro. Finally, the ternary FnCpf1-crRNA-DNA complex was assembled and purified
by preparative electrophoresis before crystallization. Crystals belonging to
space group C2221, with unit-cell parameters a = 85.2, b = 137.6, c = 320.5 A,
were obtained and subjected to preliminary diffraction experiments.
PMID- 28695851
TI - Structure of bovine cytochrome c oxidase crystallized at a neutral pH using a
fluorinated detergent.
AB - Cytochrome c oxidase (CcO) couples proton pumping to O2 reduction. Its enzymatic
activity depends sensitively on pH over a wide range. However, owing to
difficulty in crystallizing this protein, X-ray structure analyses of bovine CcO
aimed at understanding its reaction mechanism have been conducted using crystals
prepared at pH 5.7, which is significantly lower than that in the cell. Here,
oxidized CcO at pH 7.3 was crystallized using a fluorinated octyl-maltoside
derivative, and the structure was determined at 1.77 A resolution. No structural
differences between crystals obtained at the neutral pH and the acidic pH were
detected within the molecules. On the other hand, some differences in
intermolecular interactions were detected between the two types of crystal. The
influence of pH on the molecular surface is likely to contribute to the pH
dependency of the aerobic oxidation of ferrocytochrome c.
PMID- 28695852
TI - The multidrug-resistance transporter MdfA from Escherichia coli: crystallization
and X-ray diffraction analysis.
AB - The active efflux of antibiotics by multidrug-resistance (MDR) transporters is a
major pathway of drug resistance and complicates the clinical treatment of
bacterial infections. MdfA is a member of the major facilitator superfamily (MFS)
from Escherichia coli and provides resistance to a wide variety of dissimilar
toxic compounds, including neutral, cationic and zwitterionic substances. The 12
transmembrane-helix MdfA was expressed as a GFP-octahistidine fusion protein with
a TEV protease cleavage site. Following tag removal, MdfA was purified using two
chromatographic steps, complexed with a Fab fragment and further purified using
size-exclusion chromatography. MdfA and MdfA-Fab complexes were subjected to both
vapour-diffusion and lipidic cubic phase (LCP) crystallization techniques. Vapour
diffusion-grown crystals were of type II, with poor diffraction behaviour and
weak crystal contacts. LCP lipid screening resulted in type I crystals that
diffracted to 3.4 A resolution and belonged to the hexagonal space group P6122.
PMID- 28695853
TI - Crystal structure of the N-terminal domain of VqsR from Pseudomonas aeruginosa at
2.1 A resolution.
AB - VqsR is a quorum-sensing (QS) transcriptional regulator which controls QS systems
(las, rhl and pqs) by directly downregulating the expression of qscR in
Pseudomonas aeruginosa. As a member of the LuxR family of proteins, VqsR shares
the common motif of a helix-turn-helix (HTH)-type DNA-binding domain at the C
terminus, while the function of its N-terminal domain remains obscure. Here, the
crystal structure of the N-terminal domain of VqsR (VqsR-N; residues 1-193) was
determined at a resolution of 2.1 A. The structure is folded into a regular alpha
beta-alpha sandwich topology, which is similar to the ligand-binding domain (LBD)
of the LuxR-type QS receptors. Although their sequence similarity is very low,
structural comparison reveals that VqsR-N has a conserved enclosed cavity which
could recognize acyl-homoserine lactones (AHLs) as in other LuxR-type AHL
receptors. The structure suggests that VqsR could be a potential AHL receptor.
PMID- 28695854
TI - The putative polyketide cyclase MSMEG_0129 from Mycobacterium smegmatis:
purification, crystallization and X-ray crystallographic analysis.
AB - Mycobacterium tuberculosis Rv0164 has previously been identified as a human T
cell antigen that induces significant production of IFN-gamma in human peripheral
blood mononuclear cells. M. smegmatis MSMEG_0129 shares 59% sequence identity
with Rv0164. Based on sequence alignment, both proteins are predicted to be
members of the cyclase/dehydrase family, which is part of a large group of
enzymes referred to as type II polyketide synthases (PKSs). In biosynthetic
pathways mediated by type II PKSs, cyclases catalyze the conversion of linear
poly-beta-ketones to cyclized intermediates. To date, no mycobacterial type II
PKSs have been reported. Here, the goal is to determine whether these proteins
adopt similar folds to reported cyclase structures, and to this end MSMEG_0129
was cloned, expressed, purified and crystallized. An X-ray diffraction data set
was collected to 1.95 A resolution from a crystal belonging to space group P62,
with unit-cell parameters a = 109.76, b = 109.76, c = 56.5 A, alpha = 90, beta =
90, gamma = 120 degrees . Further crystallographic analysis should establish a
basis for investigating the structure and function of this putative mycobacterial
type II PKS enzyme.
PMID- 28695855
TI - 1.8 A resolution crystal structure of the carbapenem intrinsic resistance protein
CarF.
AB - The natural production of the beta-lactam antibiotic carbapenem in bacteria
involves a group of enzymes that form a synthetic pathway as well as proteins
that protect the cell from self-intoxification by the products. Here, the crystal
structure of CarF, one of the two proteins that confer resistance to synthesis of
the antibiotic in the host organism, is reported. The CarF fold places it within
a widely occurring structural family, indicating an ancient structural origin
from which the resistance function has been derived.
PMID- 28695856
TI - Crystal structure of Yersinia pestis virulence factor YfeA reveals two
polyspecific metal-binding sites.
AB - Gram-negative bacteria use siderophores, outer membrane receptors, inner membrane
transporters and substrate-binding proteins (SBPs) to transport transition metals
through the periplasm. The SBPs share a similar protein fold that has undergone
significant structural evolution to communicate with a variety of differentially
regulated transporters in the cell. In Yersinia pestis, the causative agent of
plague, YfeA (YPO2439, y1897), an SBP, is important for full virulence during
mammalian infection. To better understand the role of YfeA in infection, crystal
structures were determined under several environmental conditions with respect to
transition-metal levels. Energy-dispersive X-ray spectroscopy and anomalous X-ray
scattering data show that YfeA is polyspecific and can alter its substrate
specificity. In minimal-media experiments, YfeA crystals grown after iron
supplementation showed a threefold increase in iron fluorescence emission over
the iron fluorescence emission from YfeA crystals grown from nutrient-rich
conditions, and YfeA crystals grown after manganese supplementation during
overexpression showed a fivefold increase in manganese fluorescence emission over
the manganese fluorescence emission from YfeA crystals grown from nutrient-rich
conditions. In all experiments, the YfeA crystals produced the strongest
fluorescence emission from zinc and could not be manipulated otherwise.
Additionally, this report documents the discovery of a novel surface metal
binding site that prefers to chelate zinc but can also bind manganese.
Flexibility across YfeA crystal forms in three loops and a helix near the buried
metal-binding site suggest that a structural rearrangement is required for metal
loading and unloading.
PMID- 28695857
TI - Probing the structural basis of oxygen binding in a cofactor-independent
dioxygenase.
AB - The enzyme DpgC is included in the small family of cofactor-independent
dioxygenases. The chemistry of DpgC is uncommon as the protein binds and utilizes
dioxygen without the aid of a metal or organic cofactor. Previous structural and
biochemical studies identified the substrate-binding mode and the components of
the active site that are important in the catalytic mechanism. In addition, the
results delineated a putative binding pocket and migration pathway for the co
substrate dioxygen. Here, structural biology is utilized, along with site
directed mutagenesis, to probe the assigned dioxygen-binding pocket. The key
residues implicated in dioxygen trafficking were studied to probe the process of
binding, activation and chemistry. The results support the proposed chemistry and
provide insight into the general mechanism of dioxygen binding and activation.
PMID- 28695858
TI - Rapid cadmium SAD phasing at the standard wavelength (1 A).
AB - Cadmium ions can be effectively used to promote crystal growth and for
experimental phasing. Here, the use of cadmium ions as a suitable anomalous
scatterer at the standard wavelength of 1 A is demonstrated. The structures of
three different proteins were determined using cadmium single-wavelength
anomalous dispersion (SAD) phasing. Owing to the strong anomalous signal, the
structure of lysozyme could be automatically phased and built using a very low
anomalous multiplicity (1.1) and low-completeness (77%) data set. Additionally,
it is shown that cadmium ions can easily substitute divalent ions in ATP-divalent
cation complexes. This property could be generally applied for phasing
experiments of a wide range of nucleotide-binding proteins. Improvements in
crystal growth and quality, good anomalous signal at standard wavelengths (i.e.
no need to change photon energy) and rapid phasing and refinement using a single
data set are benefits that should allow cadmium ions to be widely used for
experimental phasing.
PMID- 28695859
TI - Octamer formation in lysozyme solutions at the initial crystallization stage
detected by small-angle neutron scattering.
AB - Solutions of lysozyme in heavy water were studied by small-angle neutron
scattering (SANS) at concentrations of 40, 20 and 10 mg ml-1 with and without the
addition of precipitant, and at temperatures of 10, 20 and 30 degrees C. In
addition to the expected protein monomers, dimeric and octameric species were
identified in solutions at the maximum concentration and close to the optimal
conditions for crystallization. An optimal temperature for octamer formation was
identified and both deviation from this temperature and a reduction in protein
concentration led to a significant decrease in the volume fractions of octamers
detected. In the absence of precipitant, only monomers and a minor fraction of
dimers are present in solution.
PMID- 28695860
TI - DNA conformational transitions inferred from re-evaluation of m|Fo| - D|Fc|
electron-density maps.
AB - Conformational flexibility of DNA plays important roles in biological processes
such as transcriptional regulation and DNA packaging etc. To understand the
mechanisms of these processes, it is important to analyse when, where and how DNA
shows conformational variations. Recent analyses have indicated that conventional
refinement methods do not always provide accurate models of crystallographic
heterogeneities and that some information on polymorphism has been overlooked in
previous crystallographic studies. In the present study, the m|Fo| - D|Fc|
electron-density maps of double-helical DNA crystal structures were calculated at
a resolution equal to or better than 1.5 A and potential conformational
transitions were found in 27% of DNA phosphates. Detailed analyses of the m|Fo| -
D|Fc| peaks indicated that some of these unassigned densities correspond to ZI <
> ZII or A/B -> BI conformational transitions. A relationship was also found
between ZI/ZII transitions and metal coordination in Z-DNA from the detected
peaks. The present study highlights that frequent transitions of phosphate
backbones occur even in crystals and that some of these transitions are affected
by the local molecular environment.
PMID- 28695861
TI - Seeing but not believing: the structure of glycerol dehydrogenase initially
assumed to be the structure of a survival protein from Salmonella typhimurium.
AB - The determination of the crystal structure of a mutant protein using phases based
on a previously determined crystal structure of the wild-type protein is often a
straightforward molecular-replacement protocol. Such a structure determination
may be difficult if there are large-scale structural differences between the wild
type and mutant proteins. In this manuscript, an interesting case is presented of
the unintentional crystallization of a contaminant protein which shared some
structural features with the presumed target protein, leading to difficulties in
obtaining a completely satisfactory molecular-replacement structure solution. It
was not immediately evident that the initial structure solution was incorrect
owing to the poor quality of the X-ray diffraction data and low resolution. The
structure was subsequently determined by improving the quality of the data and
following a sequence-independent MarathonMR protocol. The structure corresponded
to that of glycerol dehydrogenase, which crystallized as a contaminant, instead
of the presumed mutant of a survival protein encoded by Salmonella typhimurium.
The reasons why a solution that appeared to be reasonable was obtained with an
incorrect protein model are discussed. The results presented here show that a
degree of caution is warranted when handling large-scale structure-determination
projects.
PMID- 28695862
TI - Factors affecting the amplitude of the tau angle in proteins: a revisitation.
AB - The protein folded state is the result of the fine balance of a variety of
different forces. Even minor structural perturbations may have a significant
impact on the stability of these macromolecules. Studies carried out in recent
decades have led to the convergent view that proteins are endowed with a flexible
spine. One of the open issues related to protein local backbone geometry is the
identification of the factors that influence the amplitude of the tau (N-Calpha
C) angle. Here, statistical analyses performed on an updated ensemble of X-ray
protein structures by dissecting the contribution of the major factors that can
potentially influence the local backbone geometry of proteins are reported. The
data clearly indicate that the local backbone conformation has a prominent impact
on the modulation of the tau angle. Therefore, a proper assessment of the impact
of the other potential factors can only be appropriately evaluated when small
(phi, psi) regions are considered. Here, it is shown that when the contribution
of the backbone conformation is removed by considering small (phi, psi) areas, an
impact of secondary structure, as defined by DSSP, and/or the residue type on tau
is still detectable, although to a limited extent. Indeed, distinct tau-value
distributions are detected for Pro/Gly and beta-branched (Ile/Val) residues. The
key role of the local backbone conformation highlighted here supports the use of
variable local backbone geometry in protein refinement protocols.
PMID- 28695864
TI - The role of the serum testosterone levels as a predictor of prostate cancer in
patients with atypical small acinar proliferation at the first prostate biopsy.
AB - The current literature does not support the usefulness of clinical markers on
predicting which patients with atypical small acinar proliferation (ASAP) are
more likely to progress to prostate cancer (PCa). Androgens have long been
considered to be the potential risk factors for PCa. However, the role of
testosterone is controversial. The present study aims to analyze the relationship
between serum testosterone (TS) levels and the diagnosis of PCa after a first
prostate biopsy in patients affected by ASAP. This retrospective study included
143 patients diagnosed with ASAP in an initial transrectal ultrasound-guided
prostate biopsy for suspicious PCa according to the European Association of
Urology guidelines. Their TS levels, age, PSA, prostate volume, digital rectal
examination, and prostate biopsy Gleason score (GS) were collected
retrospectively for statistical analysis. All patients included in the study had
a second biopsy and were suitable for further analysis. Re-biopsy was carried out
3-6 months after the first diagnosis of ASAP. Low and normal TS groups were
composed of 29 (20.3%) and 114 (79.7%) patients, respectively. The diagnosis of
the second biopsy was ASAP in 25.2% and PCa in 36.4% of patients. The comparison
between patients with PCa and those with negative or an ASAP result in the second
biopsy reported that men with cancer had significantly higher levels of TS (P <
0.001). However, there was no statistically significant association between GS
postbiopsy and TS (P = 0.324). Our experience demonstrated that eugonadal
patients may be a clinical risk factor for the diagnosis of PCa on re-biopsy
after ASAP diagnosis than hypogonadal.
PMID- 28695865
TI - Zinner's syndrome: clinical features and imaging diagnosis.
PMID- 28695866
TI - Writing a model research paper: A roadmap.
PMID- 28695867
TI - Muscle mass changes in the critically ill patient: The role of imaging.
PMID- 28695868
TI - Major trauma: What is important for the best outcome and survival?
PMID- 28695869
TI - Evaluation of the association between a single-nucleotide polymorphism of bone
morphogenetic proteins 5 gene and risk of knee osteoarthritis.
AB - BACKGROUND: Osteoarthritis (OA) is a chronic degenerative disorder probably
affected by both genetic and environmental causes. Bone morphogenetic proteins
(BMPs) are bone-derived factors that can induce new bone formation. Single
nucleotide polymorphisms (SNPs) of BMP5 gene alters the transcriptional activity
of the BMP5 promoter that has been involved in OA susceptibility. This case
control study investigated the association of rs1470527 and rs9382564 SNP of BMP5
gene with susceptibility to knee OA (KOA). MATERIALS AND METHODS: A total of 499
cases with radiographic KOA and 458 age- and sex-matched healthy controls were
enrolled. Venous blood samples were obtained from all the cases as well as
controls for polymerase chain reaction-restriction fragment length polymorphism.
RESULTS: The genotype distribution for rs1470527 and rs9382564 SNP was
significantly different in cases and controls (P < 0.0001). Within both the SNPs
of BMP5 gene, genotype CT and TT were significantly (P < 0.0001) associated with
KOA as compared to the CC genotype. T allele of both the studied SNP was
significantly associated with KOA (P < 0.0001). The allele frequencies of
rs1470527 were 0.56(T) and 0.44(C) in cases and 0.33(T) and 0.67(C) in controls
and in rs9382564 were 0.57(C) and 0.43(T) in cases and 0.71(C) and 0.29(T) in
controls. Further in relation with clinical severity of OA, we observed
signification association of TT genotype with both visual analog scale (P <
0.0001) and Western Ontario and McMaster Universities score (P < 0.05).
CONCLUSION: Our results indicate significant association of rs1470527 and
rs9382564 polymorphism of BMP5 gene with KOA.
PMID- 28695870
TI - Deranged regulatory T-cells and transforming growth factor-beta1 levels in type 1
diabetes patients with associated autoimmune diseases.
AB - AIM: This study was designed to enumerate regulatory T-cells (Tregs) and estimate
transforming growth factor-beta1 (TGF-beta1) levels in type 1 diabetic (T1D)
patients with respect to disease duration and associated autoimmune diseases.
METHODS: One hundred and fifty patients and twenty healthy controls were
recruited in the study. The patients were subcategorized into eight categories on
the basis of disease duration (new onset [NO] and long standing [LS]) and
associated diseases, i.e., celiac disease (CD) and autoimmune thyroid disease
(AiTD). Treg cells were assessed as CD4+ CD25hi+, FOXP3+ cells and serum TGF
beta1 levels were assessed by ELISA. RESULTS: The frequency of Tregs and levels
of TGF-beta1 were significantly increased in the patients compared to the healthy
controls. Among the different categories of the patients, no significant
differences were seen for TGF- beta1 levels, but for Tregs in patients with T1D
and AiTD (P = 0.035). A significant correlation was also found between percentage
count of Tregs and TGF-beta1 levels in NO cases in all disease subcategories, but
not in LS patients. CONCLUSION: Thus, there was an increased percentage of Tregs
and serum levels of TGF-beta1 in T1D patients, irrespective of the disease
duration and associated autoimmune diseases. The significant correlation in these
two parameters at the onset of the disease, but not in LS disease, indicates that
the immunological milieu in LS autoimmune diseases is more complicated with
disease-associated conditions such as prolonged hyperglycemia, insulin therapy,
and/or continued gluten in diet. Treatment and modulation of these long-term
complications for improving immunological parameters require further research.
PMID- 28695871
TI - Psychiatric disorders and obesity: A review of association studies.
AB - BACKGROUND: Inconsistent evidence exists regarding the strength, direction, and
moderators in the relationship between obesity and psychiatric disorders. AIM:
This study aims to summarize the evidence on the association between psychiatric
illness and obesity with particular attention to the strength and direction of
association and also the possible moderators in each postulated link. MATERIALS
AND METHODS: Systematic electronic searches of MEDLINE through PubMed,
ScienceDirect, PsycINFO, and Google Scholar were carried out from inception till
October 2016. Generated abstracts were screened for eligibility to be included in
the review. Study designs that evaluated the strength of relationship between
obesity and psychiatric disorders were included in the study. Quality assessment
of included studies was done using the Newcastle-Ottawa checklist tool. RESULTS:
From a total of 2424 search results, 21 eligible articles were identified and
reviewed. These included studies on obesity and depression (n = 15), obesity and
anxiety (four) and one each on obesity and personality disorders, eating disorder
(ED), attention deficit hyperactivity disorder, and alcohol use. Maximal evidence
existed for the association between depression and obesity with longitudinal
studies demonstrating a bidirectional link between the two conditions. The odds
ratios (ORs) were similar for developing depression in obesity (OR: 1.21-5.8) and
vice versa (OR: 1.18-3.76) with a stronger association observed in women. For
anxiety disorders, evidence was mostly cross-sectional, and associations were of
modest magnitude (OR: 1.27-1.40). Among other disorders, obesity, and EDs appear
to have a close link (OR: 4.5). Alcohol use appears to be a risk factor for
obesity and not vice versa but only among women (OR: 3.84). CONCLUSION: Obesity
and depression have a significant and bidirectional association. Evidence is
modest for anxiety disorders and inadequate for other psychiatric conditions.
Gender appears to be an important mediator in these relationships.
PMID- 28695872
TI - Malignant orbital teratoma in a neonate: A clinicopathological case report.
AB - Teratoma of the orbit is rare; very few cases have been published in literature.
A case of orbital teratoma in a neonate is presented where the proptosis was
massive enough to obscure the eyeball. Clinically, the diagnosis of teratoma was
considered. As there was no possibility of salvaging the eye, exenteration of the
orbit was done. Orbital teratomas are generally benign. Histopathological
examination revealed the features of malignant teratoma.
PMID- 28695873
TI - Powdered gloves: Time to bid adieu.
PMID- 28695874
TI - Thoracoscopic management of oesophageal mucocele: Old complication, new approach.
AB - Oesophageal mucocele is an uncommon complication of bipolar exclusion of
oesophagus. Traditionally, this condition is managed through thoracotomy which is
associated with significant morbidity. The present report outlines the
thoracoscopic management of oesophageal mucocele following surgical exclusion for
oesophageal perforation. Left thoracoscopic oesophagectomy for oesophageal
mucocele described in this report has not been published earlier.
PMID- 28695875
TI - Can bariatric surgery delay the need for knee replacement in morbidly obese
osteoarthritis patients.
AB - OBJECTIVE: The objective of the study was to find the weight reduction pattern
and its outcome on knee pain and function in osteoarthritis (OA) morbidly obese
patients' post-bariatric surgery with dietary and exercise changes. METHODOLOGY:
Thirty morbidly obese (body mass index [BMI] >40 kg/m2) OA patients gave consent
for bariatric surgery. Despite wearisome lifestyle modifications for weight loss
and knee pain, satisfactory results were not retrieved. We took consent from all
the patients predetermined for knee replacement in future because of pain and
disability as recommended by knee replacement surgeon. The dietary and exercise
protocol was standardised for all patients for bariatrics. Data for weight loss,
change in BMI and Western Ontario and McMaster Universities Arthritis Index score
consisting of pain, stiffness and activities of daily livings (ADLs) scores were
documented at baseline, 3 months and 6 months post-bariatric surgery. RESULTS:
The male-to-female ratio was 1:2. Mean age of the patients was 49.8 +/- 8.6
years. Significant changes in pain (P < 0.001), stiffness (P < 0.001) and ADLs (P
< 0.001) were found postoperatively at 3 and 6 months. Positive correlation of
percentage change of BMI was seen with percentage change in pain (r = 0.479, P =
0.007) and ADLs (r = 0.414, P = 0.023) after 6 months of bariatric surgery. Most
of the patients were inclined to delay the knee replacement further by the end of
6 months post-bariatric surgery. CONCLUSION: Bariatric surgery when combined with
dietary and exercise changes gave significant results in terms of weight loss,
knee pain and function. It is an approach that tackles both obesity and OA. It is
a major step forward in stemming the global epidemic of these two interlinked
conditions.
PMID- 28695876
TI - Impact of obesity on surgical outcome after single-incision laparoscopic
cholecystectomy.
AB - Introduction: Single-incision laparoscopic cholecystectomy (SILC) is widely used
as a treatment option for gallbladder disease. However, obesity has been
considered a relative contraindication to this approach due to more advanced
technical difficulties. The aim of this report was to review our experience with
SILC to evaluate the impact of body mass index (BMI) on the surgical outcome.
Patients and Methods: Between May 2009 and February 2013, 237 patients underwent
SILC at our institute. Pre- and post-operative data of the 17 obese patients (O
group) (BMI >=30 kg/m2) and 220 non-obese patients (NO-group) (BMI <29.9 kg/m2)
were compared retrospectively. SILC was performed under general anaesthesia,
using glove technique. Indications for surgery included benign gallbladder
disease, except for emergent surgeries. Results: Mean age of patients was
significantly higher in the NO-group than O-group (58.9 +/- 13.5 years vs. 50.8
+/- 14.0 years, P = 0.025). SILC was successfully completed in 233 patients
(98.3%). Four patients (1.7%) in the NO-group required an additional port, and
one patient was converted to an open procedure. The median operative time was 70
+/- 25 min in the NO-group and 75.2 +/- 18.3 min in the O-group. All
complications were minor, except for one case in the NO-group that suffered with
leakage of the cystic duct stump, for which endoscopic nasobiliary drainage was
need. Conclusion: Our findings show that obesity, intended as a BMI >=30 kg/m2,
does not have an adverse impact on the technical difficulty and post-operative
outcomes of SILC. Obesity-related comorbidities did not increase the risks for
SILC.
PMID- 28695877
TI - Endoscopic gastric polypectomy assisted by laparoscopy for giant gastric and
duodenal lesion treatment: Case series from two centres.
AB - BACKGROUND: Endoscopy has developed rapidly, generating new challenges. Today,
there are several procedures done endoscopically with very good results. In the
past, the assisted laparoscopic colon polypectomy has been described, reducing
the morbidity of a bigger procedure. Nonetheless, little has been said about the
use of hybrid surgery in the management of gastric or duodenal polyps.
OBJECTIVES: Evaluating the safety and efficacy of the assisted laparoscopic
gastric endoscopic polypectomy. PATIENTS AND METHODS: A retrospective review of
the database at our two centres was performed from 1996 to 2014. Thirteen
patients were found in whom an assisted laparoscopic gastric or duodenal
endoscopic tumour resection was performed. RESULTS: Thirteen patients, eight
males and five females, with a median age of 61 years and average body mass index
of 29.3. The procedure was done effectively and no need for further procedures
was required for any patient. No complications were reported in the early post
operative period. CONCLUSIONS: The study shows that assisted laparoscopic gastric
endoscopic polypectomy is a feasible and safe procedure that can be used for the
management of giant polyps, which cannot be resected with the classical
endoscopic polypectomy reducing the morbidity and complications associated with
larger procedures.
PMID- 28695878
TI - Impact of biliopancreatic limb length on severe protein-calorie malnutrition
requiring revisional surgery after one anastomosis (mini) gastric bypass.
AB - BACKGROUND: One anastomosis (mini) gastric bypass (OAGB) is believed to be more
malabsorptive than Roux-en-Y gastric bypass. A number of patients undergoing this
procedure suffer from severe protein-calorie malnutrition requiring revisional
surgery. The purpose of this study was to find the magnitude of severe protein
calorie malnutrition requiring revisional surgery after OAGB and any potential
relationship with biliopancreatic limb (BPL) length. METHODS: A questionnaire
based survey was carried out on the surgeons performing OAGB. Data were further
corroborated with the published scientific literature. RESULTS: A total of 118
surgeons from thirty countries reported experience with 47,364 OAGB procedures.
Overall, 0.37% (138/36,952) of patients needed revisional surgery for
malnutrition. The highest percentage of 0.51% (120/23,277) was recorded with
formulae using >200 cm of BPL for some patients, and lowest rate of 0% was seen
with 150 cm BPL. These data were corroborated by published scientific literature,
which has a record of 50 (0.56%) patients needing surgical revision for severe
malnutrition after OAGB. CONCLUSIONS: A very small number of OAGB patients need
surgical correction for severe protein-calorie malnutrition. Highest rates of
0.6% were seen in the hands of surgeons using BPL length of >250 cm for some of
their patients, and the lowest rate of 0% was seen with BPL of 150 cm. Future
studies are needed to examine the efficacy of a standardised BPL length of 150 cm
with OAGB.
PMID- 28695879
TI - Iatrogenic injury of the intrathoracic oesophagus with bougie during sleeve
gastrectomy.
AB - One of the most popular procedures amongst obesity surgery is the sleeve
gastrectomy. There is international consensus regarding the usage of bougie for
sleeve gastrectomy calibration. Nevertheless, there is a dissociation between the
number of oesophageal perforations reported for any other oesophageal/gastric
operation that requires bougie (e.g., anti-reflux surgery, incidence 1.2%) and
bariatric surgery, where this complication seems to be almost a myth.
Interestingly enough, the number of bariatric procedures is much higher than any
other oesophageal/gastric surgery. This suggests that oesophageal perforations in
obesity surgery are underreported. We report a case of injury of the
intrathoracic oesophagus with bougie that occurred during a sleeve gastrectomy.
In the infrequent case that the perforation is diagnosed during surgery, primary
repair during the same intervention is highly recommended. Videothoracoscopy
might be an effective option in case of necessity. We were able to complete the
sleeve gastrectomy without increasing morbidity.
PMID- 28695880
TI - Hand-assisted laparoscopic restorative proctocolectomy with ileal pouch-anal
anastomosis for ulcerative colitis.
AB - INTRODUCTION: In this study, we aimed to evaluate the feasibility and safety of
undergoing restorative proctocolectomy through ileal pouch-anal anastomosis (RPC
IPAA) with hand-assisted laparoscopic (HALS) in patients with ulcerative colitis
(UC). PATIENTS AND METHODS: We reviewed 40 consecutive patients who underwent RPC
IPAA with HALS or open technique for treatment of UC between 2010 and 2013.
Moreover, the intra-/post-operative outcomes were compared. RESULTS: We found the
median operative time was significantly longer in the HALS group while the blood
loss was significantly less in patients with HALS than with open surgery. In the
HALS group, the median duration of bed rest and the length of hospital stay were
significantly shorter. Moreover, the rate of early post-operative complications
in the HALS group was significantly less than that in the open surgery group,
among which one patient died in the 30th day after surgery for the extensive use
of steroids before the operation. CONCLUSION: These findings clearly show that
HALS RPC is safe and less invasiveness. HALS can become a more comfortable and
standardised procedure for UC with the adoption of evolving technologies.
PMID- 28695881
TI - A case report of modified laparoscopic keyhole plus repair for parastomal hernia
following ileal conduit.
AB - Parastomal hernia is one of the most common but challenging complication after
stoma formation. Modified Sugarbaker technique is the recommended procedure for
repair parastomal hernia, however, keyhole repair technique had also been used in
certain instances. In cases of parastomal hernia following ileal conduit
procedure, the Sugarbaker technique is been described, although with associated
theoretical risk of conduit failure. We are reporting a case of post-radical
cystectomy with ileal conduit presented with symptomatic large parastomal hernia.
Laparoscopic modified keyhole plus repair has been done successfully in this
patient with no recurrence in 2 years of follow-up. The purpose of our case
report is to describe our novel modification of the laparoscopic keyhole
technique which can be a feasible and acceptable alternative surgical method in
these types of patients.
PMID- 28695882
TI - Institutional experience with laparoscopic-assisted anorectal pull-through in a
series of 17 cases: A retrospective analysis.
AB - AIMS: To retrospectively analyse the results of laparoscopically-assisted
anorectal pull-through (LAARP) for high anorectal malformation (ARM) in male
children in our institution. MATERIALS AND METHODS: We analysed the hospital
records of patients who had undergone LAARP from October 2010 to December 2015 in
terms of age, operative time, length of hospital stay and post-operative
complications. RESULTS: Of 17 cases, 13 (76%) were in 6-12 months age group,
whereas rest of them were in 12-18 months age group. The recto-prostatic urethral
fistula was encountered in 82% (n = 14) of patients and rectovesical type in two
cases (12%). The mean operative time was 132 min with mean length of hospital
stay being 4 days. Rectal mucosal prolapse was the most common complication
noted. CONCLUSIONS: LAARP is a feasible approach to male children with high ARMs
with less post-operative morbidity.
PMID- 28695883
TI - Single incision multiport versus conventional laparoscopic inguinal hernia
repair: A matched comparison.
AB - BACKGROUND: The popularity of single-incision procedures is on the rise as wound
cosmesis is increasingly being seen as an important body image-related outcome.
In this study, we assess the potential benefits of single-incision multiport
laparoscopic totally extra-peritoneal (S-TEP) without using specialised ports or
instruments and compare the same with the conventional laparoscopic TEP (C-TEP)
surgery in terms of operative time, post-operative pain, complications, cost and
cosmesis. MATERIALS AND METHODS: This is a prospective case-matched study of the
patients undergoing S-TEP versus C-TEP from June 2014 to December 2015. RESULTS:
Each group had 36 patients. The two groups were comparable in the clinical
characteristics. The mean duration of surgery for a unilateral hernia in C-TEP
and S-TEP was 45.13 +/- 10.58 min and 72.63 +/- 15.23 min, respectively. The mean
visual analogue scale (VAS) score for pain was significantly higher in S-TEP
group at post-operative day (POD) 0 and 1. However, at POD 7, there was no
significant difference between the groups. At 1st and 6-week post-surgery, the
cosmetic results were significantly better in S-TEP group as compared to C-TEP,
however, at 6 months, the scar was highly acceptable in both treatment groups.
CONCLUSION: S-TEP, using conventional laparoscopic instruments, is safe and
feasible even in resource challenged setting. However, there is a need to review
the indications and advantages of single-incision laparoscopic surgery, as no
difference in cosmetic outcome by VAS score in S-TEP versus conventional
laparoscopic arm seen by the end of 1 month.
PMID- 28695884
TI - Late solitary pelvic metastasis of hepatocellular carcinoma mimicking alpha
fetoprotein-producing gynaecologic tumour.
AB - Extrahepatic spread of hepatocellular carcinoma (HCC) is uncommon; and, pelvic
metastasis, in particular, is extremely rare. A 71-year-old woman was admitted
for evaluation of pelvic solitary solid mass. She had undergone a left lobectomy
28 years previously. Magnetic resonance imaging of the abdomen and pelvis
demonstrated a heterogeneous mass in the right pelvic cavity, whereas no space
occupying lesions or ascites were detected in the liver. CA 125 levels were
within normal limits; however, serum alpha-fetoprotein levels were markedly
elevated. She underwent laparoscopic pelvic mass excision, total hysterectomy,
and bilateral salpingo-oophorectomy. Histopathologic findings and immunochemical
staining results indicated metastatic HCC. Herein, we report an unusual case of a
patient with solitary recurrence in the pelvic cavity 28 years after initial
diagnosis and treatment.
PMID- 28695885
TI - Laparoscopic splenectomy for sclerosing angiomatoid nodular transformation of the
spleen.
AB - Sclerosing angiomatoid nodular transformation (SANT) is a rare, benign,
proliferative vascular lesion that arises from the splenic red pulp. Most
patients with SANT have no clinical symptoms and are discovered incidentally on
imaging. There are no definitive radiological signs and a distinction from other
splenic diseases, and malignant processes remain difficult. Confirmation of the
diagnosis of SANT requires a histological and immunohistochemical evaluation of
the resected spleen. Here, we report an unusual case of SANT of the spleen
successfully treated with an elective laparoscopic splenectomy (LS). LS is a safe
and effective method for diagnosis of SANT.
PMID- 28695886
TI - Retraction note: A Boy with Relentless Pruritus: Job's Syndrome.
PMID- 28695887
TI - A volumetric three-dimensional digital light photoactivatable dye display.
AB - Volumetric three-dimensional displays offer spatially accurate representations of
images with a 360 degrees view, but have been difficult to implement due to
complex fabrication requirements. Herein, a chemically enabled volumetric 3D
digital light photoactivatable dye display (3D Light PAD) is reported. The
operating principle relies on photoactivatable dyes that become reversibly
fluorescent upon illumination with ultraviolet light. Proper tuning of kinetics
and emission wavelengths enables the generation of a spatial pattern of
fluorescent emission at the intersection of two structured light beams. A first
generation 3D Light PAD was fabricated using the photoactivatable dye N-phenyl
spirolactam rhodamine B, a commercial picoprojector, an ultraviolet projector and
a custom quartz imaging chamber. The system displays a minimum voxel size of 0.68
mm3, 200 MUm resolution and good stability over repeated 'on-off' cycles. A range
of high-resolution 3D images and animations can be projected, setting the
foundation for widely accessible volumetric 3D displays.
PMID- 28695888
TI - Somatic chromosomal engineering identifies BCAN-NTRK1 as a potent glioma driver
and therapeutic target.
AB - The widespread application of high-throughput sequencing methods is resulting in
the identification of a rapidly growing number of novel gene fusions caused by
tumour-specific chromosomal rearrangements, whose oncogenic potential remains
unknown. Here we describe a strategy that builds upon recent advances in genome
editing and combines ex vivo and in vivo chromosomal engineering to rapidly and
effectively interrogate the oncogenic potential of genomic rearrangements
identified in human brain cancers. We show that one such rearrangement, an
microdeletion resulting in a fusion between Brevican (BCAN) and Neurotrophic
Receptor Tyrosine Kinase 1 (NTRK1), is a potent oncogenic driver of high-grade
gliomas and confers sensitivity to the experimental TRK inhibitor entrectinib.
This work demonstrates that BCAN-NTRK1 is a bona fide human glioma driver and
describes a general strategy to define the oncogenic potential of novel glioma
associated genomic rearrangements and to generate accurate preclinical models of
this lethal human cancer.
PMID- 28695889
TI - Coding GPCR-G protein specificity.
AB - G protein-coupled receptors (GPCRs) are ubiquitous gatekeepers of cellular
response and signal predominantly by recruitment and activation of G proteins. In
a recent paper in Nature, Flock et al. use large-scale bioinformatics to build a
model of GPCR-G protein selectivity and an interactive database to interrogate
potential receptor-G protein interactions.
PMID- 28695890
TI - Dual loss of human POLQ and LIG4 abolishes random integration.
AB - Homologous recombination-mediated gene targeting has greatly contributed to
genetic analysis in a wide range of species, but is highly inefficient in human
cells because of overwhelmingly frequent random integration events, whose
molecular mechanism remains elusive. Here we show that DNA polymerase theta,
despite its minor role in chromosomal DNA repair, substantially contributes to
random integration, and that cells lacking both DNA polymerase theta and DNA
ligase IV, which is essential for non-homologous end joining (NHEJ), exhibit 100%
efficiency of spontaneous gene targeting by virtue of undetectable levels of
random integration. Thus, DNA polymerase theta-mediated end joining is the sole
homology-independent repair route in the absence of NHEJ and, intriguingly, their
combined absence reveals rare Alu-Alu recombination events utilizing a stretch of
homology. Our findings provide new insights into the mechanics of foreign DNA
integration and the role of DNA polymerase theta in human genome maintenance.
PMID- 28695891
TI - The endothelial transcription factor ERG mediates Angiopoietin-1-dependent
control of Notch signalling and vascular stability.
AB - Notch and Angiopoietin-1 (Ang1)/Tie2 pathways are crucial for vascular maturation
and stability. Here we identify the transcription factor ERG as a key regulator
of endothelial Notch signalling. We show that ERG controls the balance between
Notch ligands by driving Delta-like ligand 4 (Dll4) while repressing Jagged1
(Jag1) expression. In vivo, this regulation occurs selectively in the maturing
plexus of the mouse developing retina, where Ang1/Tie2 signalling is active. We
find that ERG mediates Ang1-dependent regulation of Notch ligands and is required
for the stabilizing effects of Ang1 in vivo. We show that Ang1 induces ERG
phosphorylation in a phosphoinositide 3-kinase (PI3K)/Akt-dependent manner,
resulting in ERG enrichment at Dll4 promoter and multiple enhancers. Finally, we
demonstrate that ERG directly interacts with Notch intracellular domain (NICD)
and beta-catenin and is required for Ang1-dependent beta-catenin recruitment at
the Dll4 locus. We propose that ERG coordinates Ang1, beta-catenin and Notch
signalling to promote vascular stability.
PMID- 28695892
TI - Targeted DNA methylation in vivo using an engineered dCas9-MQ1 fusion protein.
AB - Comprehensive studies have shown that DNA methylation plays vital roles in both
loss of pluripotency and governance of the transcriptome during embryogenesis and
subsequent developmental processes. Aberrant DNA methylation patterns have been
widely observed in tumorigenesis, ageing and neurodegenerative diseases,
highlighting the importance of a systematic understanding of DNA methylation and
the dynamic changes of methylomes during disease onset and progression. Here we
describe a facile and convenient approach for efficient targeted DNA methylation
by fusing inactive Cas9 (dCas9) with an engineered prokaryotic DNA
methyltransferase MQ1. Our study presents a rapid and efficient strategy to
achieve locus-specific cytosine modifications in the genome without obvious
impact on global methylation in 24 h. Finally, we demonstrate our tool can induce
targeted CpG methylation in mice by zygote microinjection, thereby demonstrating
its potential utility in early development.
PMID- 28695893
TI - Dorsal Hippocampus Drives Context-Induced Cocaine Seeking via Inputs to Lateral
Septum.
AB - Lateral septum (LS) has re-emerged as an important structure in reward and
addiction; however, LS afferents that drive addiction behaviors are unknown.
Here, we used a modified self-administration/reinstatement procedure combined
with anatomical, pharmacological, and chemogenetic techniques to characterize LS,
and hippocampal inputs to LS, in two established triggers of drug relapse-context
and cue-induced reinstatement of cocaine seeking. We found that inactivation of
LS neurons attenuated both context- and cue-induced reinstatement of cocaine
seeking. However, dorsal hippocampus inputs to LS showed enhanced neuronal
activation (as measured by Fos expression) during context-induced, but not cue
induced reinstatement. Additionally, chemogenetic inhibition of dorsal, but not
ventral, hippocampal inputs to LS specifically attenuated context-induced
reinstatement. Together these findings elucidate the importance of LS in
reinstatement of cocaine seeking, and indicate that dorsal hippocampal inputs to
LS mediate context-, but not cue-induced, reinstatement of cocaine seeking.
PMID- 28695894
TI - Enhanced electron dephasing in three-dimensional topological insulators.
AB - Study of the dephasing in electronic systems is not only important for probing
the nature of their ground states, but also crucial to harnessing the quantum
coherence for information processing. In contrast to well-studied conventional
metals and semiconductors, it remains unclear which mechanism is mainly
responsible for electron dephasing in three-dimensional topological insulators
(TIs). Here, we report on using weak antilocalization effect to measure the
dephasing rates in highly tunable (Bi,Sb)2Te3 thin films. As the transport is
varied from a bulk-conducting regime to surface-dominant transport, the dephasing
rate is observed to evolve from a linear temperature dependence to a sublinear
power-law dependence. Although the former is consistent with the Nyquist electron
electron interactions commonly seen in ordinary 2D systems, the latter leads to
enhanced electron dephasing at low temperatures and is attributed to the coupling
between the surface states and the localized charge puddles in the bulk of 3D
TIs.
PMID- 28695895
TI - Corrigendum: Synthesis of Sr2Si5N8: Ce3+ phosphors for white LEDs via efficient
chemical vapor deposition.
AB - This corrects the article DOI: 10.1038/srep45832.
PMID- 28695896
TI - R-Spondin chromosome rearrangements drive Wnt-dependent tumour initiation and
maintenance in the intestine.
AB - Defining the genetic drivers of cancer progression is a key in understanding
disease biology and developing effective targeted therapies. Chromosome
rearrangements are a common feature of human malignancies, but whether they
represent bona fide cancer drivers and therapeutically actionable targets,
requires functional testing. Here, we describe the generation of transgenic,
inducible CRISPR-based mouse systems to engineer and study recurrent colon cancer
associated EIF3E-RSPO2 and PTPRK-RSPO3 chromosome rearrangements in vivo. We show
that both Rspo2 and Rspo3 fusion events are sufficient to initiate hyperplasia
and tumour development in vivo, without additional cooperating genetic events.
Rspo-fusion tumours are entirely Wnt-dependent, as treatment with an inhibitor of
Wnt secretion, LGK974, drives rapid tumour clearance from the intestinal mucosa
without effects on normal intestinal crypts. Altogether, our study provides
direct evidence that endogenous Rspo2 and Rspo3 chromosome rearrangements can
initiate and maintain tumour development, and indicate a viable therapeutic
window for LGK974 treatment of RSPO-fusion cancers.
PMID- 28695897
TI - Erratum: ACF7 regulates inflammatory colitis and intestinal wound response by
orchestrating tight junction dynamics.
AB - This corrects the article DOI: 10.1038/ncomms15375.
PMID- 28695898
TI - CDPs: caspase-dependent non-lethal cellular processes.
PMID- 28695899
TI - Innate scavenger receptor-A regulates adaptive T helper cell responses to
pathogen infection.
AB - The pattern recognition receptor (PRR) scavenger receptor class A (SR-A) has an
important function in the pathogenesis of non-infectious diseases and in innate
immune responses to pathogen infections. However, little is known about the role
of SR-A in the host adaptive immune responses to pathogen infection. Here we show
with mouse models of helminth Schistosoma japonicum infection and heat
inactivated Mycobacterium tuberculosis stimulation that SR-A is regulated by
pathogens and suppresses IRF5 nuclear translocation by direct interaction.
Reduced abundance of nuclear IRF5 shifts macrophage polarization from M1 towards
M2, which subsequently switches T-helper responses from type 1 to type 2. Our
study identifies a role for SR-A as an innate PRR in regulating adaptive immune
responses.
PMID- 28695900
TI - Reliability, validity and sensitivity to change of neurogenic bowel dysfunction
score in patients with spinal cord injury.
AB - STUDY DESIGN: Psychometrics study. OBJECTIVES: The aim of this study is to
investigate the validity, reliability and sensitivity to change of neurogenic
bowel dysfunction (NBD) score. SETTING: Dokuz Eylul University Faculty of
Medicine, Turkey. METHODS: The study included 42 patients with spinal cord injury
(SCI). The reliability of NBD score was assessed by test-retest reliability and
internal consistency. Cronbach's alpha coefficient was calculated to determine
internal consistency. The construct validity was evaluated by exploring
correlations between the NBD score and SF-36 scales, patient assessment of impact
of NBD on quality of life (QoL) and the physician global assessment (PGA). The
Global Rating of Change (GRC) scale was used to assess the change of NBD to
investigate the sensitivity of the score to change. RESULTS: Cronbach's alpha
coefficient was 0.547. In test-retest reliability analysis, high correlations
between total test-retest NBD score and answers of each question were found
(r=1.000, P<0.001). NBD score had a strong and significant correlation with PGA
(r=0.98, P<0.000) and the impact on QoL (r=0.92, P<0.001). There was a
significant negative correlation between NBD score and subscales of SF-36
(P<0.05) except physical functioning, physical role functioning and physical
component summary score. There was a significant improvement in NBD scores after
treatment (P=0.011). A significant positive correlation was found between GRC
scale and change in total NBD score (r=0.821, P=0.007). CONCLUSION: The Turkish
version of the NBD score is a valid and reliable instrument and also sensitive to
change in patients with SCI.
PMID- 28695901
TI - Development and validation of a bowel-routine-based self-report questionnaire for
sacral sparing after spinal cord injury.
AB - STUDY DESIGN: An observational study. OBJECTIVE: To develop a self-administered
tool for assessment of sacral sparing after spinal cord injury (SCI) and to test
its validity in individuals with SCI. SETTING: Peking University Third Hospital,
Beijing, China. METHODS: A 5-item SCI sacral sparing self-report questionnaire
was developed based on several events that most patients might experience during
bowel routine. 102 participants who sustained SCI within 12 months were asked to
complete the questionnaire followed by an anorectal examination. Agreements of
answers to the questionnaire and the physical examination were analyzed.
Sensitivity, specificity and Youden's index of each item was calculated. RESULTS:
The first four questions regarding the S4-5 sensation including deep anal
pressure showed high agreement with the results of the physical examination
(kappa: 0.79-0.93). Sensitivity, specificity and Youden's index were also high
(all above 80%). For the fifth question related to the voluntary anal
contraction, the agreement was almost perfect with good sensitivity and
specificity among patients without increased anal sphincter tone (AST). In
patients with increased AST, the agreement was fair. CONCLUSION: The validity of
this questionnaire for the assessment of sacral sparing in up to 12 months post
injury is good except for the motor function when there was increased AST. In
some situations it could be considered as an alternative tool for digital rectal
examination, especially when repeated examinations are not feasible. It is
suggested that change of sacral sparing may be detected by the questionnaire.
PMID- 28695902
TI - Methods for classifying obesity in spinal cord injury: a review.
AB - STUDY DESIGN: Narrative review. OBJECTIVES: Review methods used to measure and
classify obesity in individuals with spinal cord injuries (SCI). Outline the
strengths and weaknesses of each method used to measure obesity in individuals
with SCI. SETTING: International. METHODS: PubMed was used to identify articles
before 2016. Search terms ('obesity' or 'weight status' and 'spinal cord
injury'). Filters: adults, English and human. Studies were retained that (1)
included participants, 18 years or older, with SCI; (2) took place in inpatient,
outpatient or community-based settings and (3) measured obesity status. Unique
methods for classifying individuals with SCI as obese were identified and
examples are presented. RESULTS: Methods identified for classifying obesity were
as follows: World Health Organization body mass index (BMI) cutoff?30 kg m-2, BMI
cutoff ?25-29 kg m-2, and SCI-specific BMI cutoff ?22 kg m-2, waist circumference
cutoff (women >102 cm, men >88 cm), percent body fat cutoffs ?25% using
bioelectrical impedance analysis and dual-energy X-ray absorptiometry,
computerized tomography scan visceral fat area ?100 cm2 and percentage of ideal
body weight. CONCLUSIONS: BMI is the most widely used measure of obesity in the
SCI literature. Although some studies identified alternative cutoffs or other
metrics, there is no standardized obesity classification in SCI. However,
research is needed to determine and validate obesity classification specific to
SCI due to physiological changes that occur following injury. We recommend that
researchers and clinicians proceed with caution and use methodology based on the
purpose of measurement.
PMID- 28695903
TI - Social support and its association with depression, gender and socioeconomic
indicators in individuals with spinal cord injury in Iran.
AB - STUDY DESIGN: Descriptive cross-sectional study. OBJECTIVES: To investigate the
relationship between perceived social support and depression and to evaluate the
role of family, friends and other caregivers in the perception of social support
in Iranian individuals with spinal cord injury (SCI). SETTING: Brain and Spinal
Cord Injury Research Center, Tehran University of Medical Sciences, Tehran, Iran.
METHODS: Social support was evaluated using the Multidimensional Scale of
Perceived Social Support questionnaire, which gauges perceptions of support from
family, friends and 'important persons'. The presence and severity of depression
were assessed with the Beck Depression Inventory (BDI-II-PERSIAN)-a 21-item
multiple-choice questionnaire. RESULTS: A total of 140 individuals with SCI were
enrolled in the study. The average age of the participants was 29.4+/-7.9 years;
the mean duration of injury was 46.3+/-46.5 months and most patients were male
(72%). Social support and all subscales of social support were numerically
greater in males; however, this difference was not statistically significant. The
subcategory of friends' support in men was 17.9+/-7.9 compared to 14.6+/-8.0 in
women (P=0.04). The self-reported social support score (r=-0.387, P<0.001) and
subscales of social support, including family (r=-0.174, P=0.045), friends (r=
0.356, P<0.001) and important persons (r=-0.373, P<0.001), were all negatively
correlated with depression. CONCLUSION: Higher self-reported perception of social
support appears to be associated with lower levels of depression in individuals
with SCI. SCI care providers should consider the relationship between social
support and depression in their continuing care.
PMID- 28695904
TI - Neuropathic pain and spasticity: intricate consequences of spinal cord injury.
AB - STUDY DESIGN: The 2016 International Spinal Cord Society Sir Ludwig Guttmann
Lecture. OBJECTIVES: The aim of this review is to identify different symptoms and
signs of neuropathic pain and spasticity after spinal cord injury (SCI) and to
present different methods of assessing them. The objective is to discuss how a
careful characterization of different symptoms and signs, and a better
translation of preclinical findings may improve our understanding of the complex
and entangled mechanisms of neuropathic pain and spasticity. METHODS: A MEDLINE
search was performed using the following terms: 'pain', 'neuropathic',
'spasticity', 'spasms' and 'spinal cord injury'. RESULTS: This review identified
different domains of neuropathic pain and spasticity after SCI and methods to
assess them in preclinical and clinical research. Different factors important for
pain description include location, onset, pain descriptors and somatosensory
function, while muscle tone, spasms, reflexes and clonus are important aspects of
spasticity. Similarities and differences between neuropathic pain and spasticity
are discussed. CONCLUSIONS: Understanding that neuropathic pain and spasticity
are multidimensional consequences of SCI, and a careful examination and
characterization of the symptoms and signs, are a prerequisite for understanding
the relationship between neuropathic pain and spasticity and the intricate
underlying mechanisms.
PMID- 28695905
TI - Corrigendum: Ganoderma lucidum reduces obesity in mice by modulating the
composition of the gut microbiota.
AB - This corrects the article DOI: 10.1038/ncomms8489.
PMID- 28695906
TI - No Association Between Proton Pump Inhibitor Use and Risk of Alzheimer's Disease.
AB - OBJECTIVES: The objective of the study was to investigate whether proton pump
inhibitor (PPI) use is associated with an increased risk of clinically verified
Alzheimer's disease (AD). METHODS: A Finnish nationwide nested case-control study
MEDALZ includes all community-dwelling individuals with newly diagnosed AD during
2005-2011 (N=70,718), and up to four age-, sex-, and region of residence-matched
comparison individuals for each case (N=282,858). Data were extracted from
Finnish nationwide health-care registers. PPI use was derived from purchases
recorded in the Prescription register data since 1995 and modeled to drug use
periods with PRE2DUP method. AD was the outcome measure. RESULTS: PPI use was not
associated with risk of AD with 3-year lag window applied between exposure and
outcome (adjusted odds ratio (OR) 1.03, 95% confidence interval (CI) 1.00-1.05).
Similarly, longer duration of use was not associated with risk of AD (1-3 years
of use, adjusted OR 1.01 (95% CI 0.97-1.06); >=3 years of use adjusted OR 0.99
(95% CI 0.94-1.04)). Higher dose use was not associated with an increased risk
(>=1.5 defined daily doses per day, adjusted OR 1.03 (95% CI 0.92-1.14)).
CONCLUSIONS: In conclusion, we found no clinically meaningful association between
PPI use and risk of AD. The results for longer duration of cumulative use or use
with higher doses did not indicate dose-response relationship.
PMID- 28695907
TI - Overuse of Repeat Upper Endoscopy in the Veterans Health Administration: A
Retrospective Analysis.
AB - OBJECTIVES: Americans undergo ~7 million esophagogastroduodenoscopies (EGDs)
annually, and one-third of Medicare beneficiaries undergo a repeat EGD within 3
years. As many as 43% of these repeat EGDs are inappropriate. We aimed to
determine the rate of repeat inappropriate EGD within the Veterans Health
Administration (VHA), and identify factors associated with repeat EGD. METHODS:
We conducted retrospective analyses of Veterans undergoing an index EGD at 159
VHA facilities between 1 January 2003 and 30 June 2007. We excluded Veterans
without regular use of VHA for health care or 5 years of follow-up.
Appropriateness of repeat EGDs was classified based on diagnostic and procedure
codes into three categories: Likely Appropriate, Possible Overuse, and Probable
Overuse. The proportion of repeat EGDs in each category was tabulated. Multilevel
logistic regression was performed to estimate the impact of patient-level and
site-level factors on the odds of repeat EGD. RESULTS: Of the 235,855 included
Veterans, 85,690 (36.3%) underwent a repeat EGD within 5 years. Of the repeat
EGDs, 42,412 (49.5%) were Likely Appropriate, 35,503 (41.4%) represented Possible
Overuse, and 7,756 (9.1%) represented Probable Overuse. Patients with more
frequent encounters with primary care providers and access to facilities
performing EGD and with greater complexity of services were more likely to
receive repeat EGD, regardless of whether the repeat EGD was appropriate or
overuse. Women were slightly more likely to undergo repeat EGD in Probable
Overuse situations. CONCLUSIONS: Overuse of repeat EGD is common in VHA despite
the absence of financial incentives that promote overuse. Efforts are needed to
better understand the motivations for overuse and barriers to appropriate use,
and to promote appropriate use of repeat EGD.
PMID- 28695908
TI - Long-Term Colorectal Cancer Incidence After Negative Colonoscopy in the State of
Utah: The Effect of Family History.
AB - OBJECTIVES: Colonoscopy is widely recommended for colorectal cancer (CRC)
screening, but evidence to guide the optimal frequency of repeat screening
examination is limited. We examined the duration and magnitude of the risk of
developing CRC, following a negative colonoscopy in those at average risk and
those with a first-degree family history of CRC. METHODS: A cohort of Utah
residents aged 50-80 years who had a negative colonoscopy between 1 January 2001
and 31 December 2011 was identified using the Utah Population Database. Patients
were followed from the time of the index colonoscopy until diagnosis of CRC,
death, migration out of state, repeat colonoscopy, or end of the study period.
CRC incidence after the index colonoscopy was compared with that of the state
population by standardized incidence ratios (SIRs). RESULTS: A cohort of 131,349
individuals at average risk with a negative colonoscopy was identified. Compared
with the state population, a negative colonoscopy was associated with SIRs of
0.15 (95% confidence interval (CI): 0.08-0.23) at 1 year, 0.26 (95% CI: 0.19
0.32) at 2-5 years, 0.33 (95% CI: 0.22-0.43) at 5-6 years, and 0.60 (95% CI: 0.44
0.76) at 7-10 years for CRC following the index colonoscopy. In a secondary
analysis involving only patients with a first-degree relative with CRC, patients
had a significantly lower incidence of CRC only for the first 5 years of follow
up (SIR 0.39, 95% CI: 013-0.64). There was also a difference in the risk of
proximal (SIR 0.72, 95% CI: 0.45-0.98) and distal (SIR 0.51, 95% CI: 0.30-0.72)
colon cancers at 7-10 years following a negative colonoscopy. CONCLUSIONS: The
risk of developing CRC remains decreased for at least 10 years following the
performance of a negative colonoscopy. However, the lower incidence of CRC in
those with a family history of CRC differed in magnitude and timing being limited
primarily to the first 5 years of follow-up and of lesser magnitude than that in
the overall cohort.
PMID- 28695910
TI - Haematological cancer: Feasible mutation-targeted therapy.
PMID- 28695909
TI - Erratum: Speckle-modulating optical coherence tomography in living mice and
humans.
AB - This corrects the article DOI: 10.1038/ncomms15845.
PMID- 28695911
TI - Haematological cancer: Low-dose CAR T cells are safe and effective.
PMID- 28695912
TI - Targeted therapy: ctDNA identified in patients with CUP.
PMID- 28695913
TI - Melanoma: Neadjuvant BRAF inhibition enables resection.
PMID- 28695914
TI - Genetics: BRCA-mutant breast/ovarian cancer revealed.
PMID- 28695915
TI - Targeted therapies: Lenvatinib SELECTs survival benefit.
PMID- 28695916
TI - The impact of sociodemographic factors and PSA screening among low-income Black
and White men: data from the Southern Community Cohort Study.
AB - BACKGROUND: Variation in PSA screening is a potential source of disparity in
prostate cancer survival, particularly among underserved populations. We sought
to examine the impact of race and socioeconomic status (SES) on receipt of PSA
testing among low-income men. METHODS: Black (n=22 167) and White (n=9588) men
aged ?40 years completed a baseline questionnaire from 2002 to 2009 as part of
the Southern Community Cohort Study. Men reported whether they had ever received
PSA testing and had testing within the prior 12 months. To evaluate the
associations between SES, race and receipt of PSA testing, odds ratios (ORs) and
95% confidence intervals (CIs) were estimated from the multivariable logistic
models where age, household income, insurance status, marital status, body mass
index and educational level were adjusted. RESULTS: Black men were younger, had a
lower income, less attained education and were more likely to be unmarried and
uninsured (all P<0.001). Percentages of men having ever received PSA testing rose
from <40% under the age of 45 years to ~90% above the age of 65 years, with
Whites >50 more likely than Blacks to have received testing. Lower SES was
significantly associated with less receipt of PSA testing in both groups. After
adjustment for SES, White men had significantly lower odds of PSA testing (OR
0.81; 95% CI: 0.76-0.87). CONCLUSIONS: Greater PSA testing among White than Black
men over the age of 50 years in this low-income population appears to be mainly a
consequence of SES. Strategies for PSA screening may benefit from tailoring to
the social circumstances of the men being screened.
PMID- 28695918
TI - Infection: The urinary microbiota is unique and resilient.
PMID- 28695917
TI - Escherichia coli FtsA forms lipid-bound minirings that antagonize lateral
interactions between FtsZ protofilaments.
AB - Most bacteria divide using a protein machine called the divisome that spans the
cytoplasmic membrane. Key divisome proteins on the membrane's cytoplasmic side
include tubulin-like FtsZ, which forms GTP-dependent protofilaments, and actin
like FtsA, which tethers FtsZ to the membrane. Here we present genetic evidence
that in Escherichia coli, FtsA antagonizes FtsZ protofilament bundling in vivo.
We then show that purified FtsA does not form straight polymers on lipid
monolayers as expected, but instead assembles into dodecameric minirings, often
in hexameric arrays. When coassembled with FtsZ on lipid monolayers, these FtsA
minirings appear to guide FtsZ to form long, often parallel, but unbundled
protofilaments, whereas a mutant of FtsZ (FtsZ*) with stronger lateral
interactions remains bundled. In contrast, a hypermorphic mutant of FtsA (FtsA*)
forms mainly arcs instead of minirings and enhances lateral interactions between
FtsZ protofilaments. Based on these results, we propose that FtsA antagonizes
lateral interactions between FtsZ protofilaments, and that the oligomeric state
of FtsA may influence FtsZ higher-order structure and divisome function.
PMID- 28695919
TI - Kidney cancer: Savolitinib - a saviour for papillary RCC?
PMID- 28695920
TI - Pharmacology: Cardiovascular effects of mirabegron.
PMID- 28695921
TI - Science and society: Development of the Asian Men's Health Report: challenges and
opportunities.
AB - Men have shorter life expectancy and higher mortality than women; however, only a
few countries have dedicated men's health policies. Men's health reports can
support the development of men's health policies. The 2013 Asian Men's Health
Report (AMHR) systematically documents and compares the status of men's health
across countries in Asia. The AMHR can be used as an exemplar to guide future
men's health reports. The main challenges during creation of the AMHR were the
lack of comprehensive health databases and the variety of data quality between
countries. The AMHR revealed variations in mortality and morbidity across
diseases, regions, and income groups, prompting a Delphi survey among men's
health stakeholders to determine whether any dedicated men's health policies in
Asia existed and to reach a consensus on the recommendations of men's health
policies. The AMHR helped to promote men's health in Asia and across the world,
generated research questions and collaborations, provided evidence to support
development of men's health policies, identified the need to improve existing
health databases, and developed a framework for the creation of other men's
health reports.
PMID- 28695922
TI - Erratum: Tracking the T-cell repertoire after adoptive therapy.
AB - [This corrects the article DOI: 10.1038/cti.2017.16.].
PMID- 28695923
TI - Erratum: The circulating life of a memory T-follicular helper cell.
AB - [This corrects the article DOI: 10.1038/cti.2017.17.].
PMID- 28695925
TI - Anti-inflammatory effects of an ethanol extract of Aster glehni via inhibition of
NF-kappaB activation in mice with DSS-induced colitis.
AB - Although Aster glehni has been reported to prevent diabetes mellitus,
hypercholesterolemia, insomnia, and cardiovascular disease, the anti-inflammatory
effect of Aster glehni in colonic tissue remains unclear. In this study, we
investigated the anti-inflammatory effects and the underlying molecular mechanism
of an ethanol extract of Aster glehni (AG) in mice with dextran sulfate sodium
(DSS)-induced colitis. AG significantly attenuated DSS-induced DAI scores, which
implied that it suppressed diarrhea, gross bleeding, and the infiltration of
immune cells. AG administration also effectively prevented shortening of the
colon length and enlargement of the spleen size. Histological examinations
indicated that AG suppressed colonic damage and the thickness of the muscle layer
induced by DSS. In addition, AG inhibited the production of pro-inflammatory
cytokines, such as TNF-alpha, IL-1beta, and IL-6, and the protein expression of
COX-2 and iNOS in mice with DSS-induced colitis. Administration with AG
suppressed the activation of nuclear factor-kappaB (NF-kappaB) including the
nuclear translocation of the p65 NF-kappaB subunit, phosphorylation and
degradation of IkappaB-alpha. Taken together, these findings suggest that the
anti-inflammatory effects of AG are mainly related to the inhibition of the
expressions of inflammatory mediators via NF-kappaB inactivation, and support its
possible therapeutic application in colitis.
PMID- 28695926
TI - Efficient multicolor tunability of ultrasmall ternary-doped LaF3 nanoparticles:
energy conversion and magnetic behavior.
AB - Luminescence-tunable multicolored LaF3:xCe3+,xGd3+,yEu3+ (x = 5; y = 1, 5, 10,
and 15 mol%) nanoparticles have been synthesized via a low cost polyol method.
Powder X-ray diffraction and high-resolution transmission electron microscopy
studies confirm the hexagonal phase of the LaF3:xCe3+,xGd3+,yEu3+ nanophosphors
with average sizes (oval shape) ranging from 5 to 7 nm. Energy-dispersive X-ray
spectroscopy analyses show the uniform distribution of Ce3+, Gd3+, and Eu3+
dopants in the LaF3 host matrix. The photoluminescence spectra and electron
paramagnetic resonance measurements guarantee the presence of Eu2+, corroborated
through DC susceptibility measurements of the samples displaying paramagnetic
behavior at 300 K, whereas weak ferromagnetic ordering is shown at 2 K. The non
radiative energy transfer processes from the 4f(2F5/2) -> 5d state (Ce3+) to the
intraconfigurational 4f excited levels of rare earth ions and simultaneous
emissions in the visible region from the 4f65d1 (Eu2+) and 5D0 (Eu3+) emitting
levels, leading to overlapped broad and narrow emission bands, have been
proclaimed. The energy transfer mechanism proposes involvement of the Gd3+ ion
sub-lattice as the bridge and finally trapping by Eu2+/3+, upon excitation of the
Ce3+ ion. The calculation of experimental intensity parameters (Omega2,4) has
been discussed and the highest emission quantum efficiency (eta = 85%) of the
Eu3+ ion for the y = 10 mol% sample is reported. The advantageous existence of
the Eu2+/Eu3+ ratio along with variously doped nanomaterials described in this
work, results in tunable emission color in the blue-white-red regions,
highlighting the potential application of the samples in solid-state lighting
devices, scintillation devices, and multiplex detection.
PMID- 28695927
TI - A 3D-printed mini-hydrocyclone for high throughput particle separation:
application to primary harvesting of microalgae.
AB - The separation of micro-sized particles in a continuous flow is crucial part of
many industrial processes, from biopharmaceutical manufacturing to water
treatment. Conventional separation techniques such as centrifugation and membrane
filtration are largely limited by factors such as clogging, processing time and
operation efficiency. Microfluidic based techniques have been gaining great
attention in recent years as efficient and powerful approaches for particle
liquid separation. Yet the production of such systems using standard micro
fabrication techniques is proven to be tedious, costly and have cumbersome user
interfaces, which all render commercialization difficult. Here, we demonstrate
the design, fabrication and evaluation based on CFD simulation as well as
experimentation of 3D-printed miniaturized hydrocyclones with smaller cut-size
for high-throughput particle/cell sorting. The characteristics of the mini
cyclones were numerically investigated using computational fluid dynamics (CFD)
techniques previously revealing that reduction in the size of the cyclone results
in smaller cut-size of the particles. To showcase its utility, high-throughput
algae harvesting from the medium with low energy input is demonstrated for the
marine microalgae Tetraselmis suecica. Final microalgal biomass concentration was
increased by 7.13 times in 11 minutes of operation time using our designed
hydrocyclone (HC-1). We expect that this elegant approach can surmount the
shortcomings of other microfluidic technologies such as clogging, low-throughput,
cost and difficulty in operation. By moving away from production of planar
microfluidic systems using conventional microfabrication techniques and embracing
3D-printing technology for construction of discrete elements, we envision 3D
printed mini-cyclones can be part of a library of standardized active and passive
microfluidic components, suitable for particle-liquid separation.
PMID- 28695929
TI - Biomolecule-mediated hydrothermal synthesis of polyoxoniobate-CdS nanohybrids
with enhanced photocatalytic performance for hydrogen production and RhB
degradation.
AB - Using a biomolecule of l-cystine as the sulfur source and coordinating agent,
polyoxoniobate-CdS nanohybrids were successfully synthesized under mild
hydrothermal conditions. The adsorption of ammonium group (-NH2) in l-cystine
molecular structure on the surface of CdS renders the amine-anchored CdS
positively charged, which readily combines with the negatively charged
polyoxoniobate clusters in terms of the electrostatic interaction. The as
obtained polyoxoniobate-CdS nanohybrids exhibit much superior activity for H2
evolution and RhB degradation under visible light as compared to the unhybridized
CdS and polyoxoniobate. After co-loading Nb6 and NiS as cocatalyst, the H2
evolution activity of the nanohybrids is further increased up to 39 times as high
as that of naked CdS, which can be attributed to an enhanced electron-transfer by
adopting polyoxoniobate as electron-acceptor to retard the electron-hole
recombination. The work may open an avenue for the green synthesis of cost
effective POMs-CdS nanohybrid photocatalysts for solar energy applications.
PMID- 28695930
TI - A dual-ion electrochemistry deionization system based on AgCl-Na0.44MnO2
electrodes.
AB - Novel desalination technologies with high ion removal capacity and low energy
consumption are desirable to tackle the water shortage challenge. Herein, we
report a dual-ion electrochemistry deionization (DEDI) system with silver
chloride as the electrochemical chloride release/capture anode, sodium manganese
oxide as the electrochemical sodium release/capture cathode, and flow salt
solution as the electrolyte. Sodium and chloride ions are synergistically
released to the flow electrolyte feed at an applied positive current. Under
negative current conditions, the two ions are extracted from the flow electrolyte
feed to their corresponding electrodes at the same time, which can cause a
conductivity decrease indicating salt removal. The salt absorption/desorption
capacity of the novel deionization system is stable and reversible, up to 57.4 mg
g-1 for 100 cycles, which is much higher than that obtained by conventional or
hybrid capacitive deionization devices. The charge efficiency is 0.979/0.956
during the salt desorption/absorption process. This research will be of great
significance for high efficiency and low energy consumption seawater
desalination.
PMID- 28695931
TI - Methods of protein corona isolation for magnetic nanoparticles.
AB - Nanoparticles (NPs) in contact with a biological environment get covered by
proteins and some are loosely bound and some are tightly bound. The latter form a
hard protein corona (HPC) which is known to determine their biological behavior.
Therefore, in order to study the biological behaviour of NPs one needs to start
from the HPC. However, established methods and standards of HPC isolation are
still not known. This is especially a challenge in the case of magnetic NPs which
form a major branch of nanomedicine. Therefore, we developed a novel HPC
isolation method, a multi-step centrifugation method (MSCM), for single-domain
magnetic NPs. The MSCM was applied to iron oxide NPs in interaction with human
blood and lymph serum with different dilutions in triplicate. The analysis of the
composition of the obtained HPCs showed the reproducibility of the MSCM. This new
method was also compared with the existing magnetic separation method (MagSep)
and a study of the obtained HPC allowed us to establish the validity limits of
MagSep and MSCM on only superparamagnetic NPs and on any single-domain magnetic
NPs, respectively. Surprisingly, the HPCs obtained by these two isolation methods
were quite different, up to 50%, suggesting that only these proteins, which are
found in the HPCs of both isolation methods, are in fact real HPCs.
PMID- 28695932
TI - Luminescent lanthanide metal-organic frameworks for chemical sensing and toxic
anion detection.
AB - Prototype lanthanide metal-organic frameworks (LnMOFs), Ln(BTC) (Ln = Eu and Tb;
BTC = benzene-1,3,5-tricarboxylate), have been considered as luminescent sensors
for detecting toxic anions, while their neutral pore structures have limited the
entrance and encapsulation of anions to produce highly anion-responsive
photoluminescence (PL). To facilitate anions to enter the pore space of Ln(BTC),
a one-pot synthesis method was proposed in which BTC was partially replaced with
its structural analogue L.BF4 (H3L.BF4 = 2,4,6-tricarboxy-1-methylpyridinium
tetrafluoroborate) which consists of an anion affinity site of cationic
methylpyridinium. Compared to the original Ln(BTC), the co-doped cationic
framework Eu0.05Tb0.95-BTC0.9L0.1 is highly sensitive for detecting different
toxic anions by tuning the energy absorption of organic chromophores, the energy
transfer efficiency to Ln3+ ions and the energy allocation between different Ln3+
ions in the PL spectra. We demonstrated that the Eu0.05Tb0.95-BTC0.9L0.1 PL
sensor has the capability of decoding various toxic anions with a clearly
differentiable and unique emission intensity ratio of 5D4 -> 7F5 (Tb3+, 545 nm)
to 5D0 -> 7F2 (Eu3+, 618 nm) transitions (ITb/IEu). Compared to Ln(BTC), the co
doped Eu0.05Tb0.95-BTC0.9L0.1 presents self-calibrating, high distinguishable and
stable PL signals for detecting toxic anions.
PMID- 28695933
TI - Kinetic characterisation of a dye decolourising peroxidase from Streptomyces
lividans: new insight into the mechanism of anthraquinone dye decolourisation.
AB - Dye decolourising peroxidases are the most recent family of haem peroxidases to
be discovered. The oxidising potential of these enzymes is driven by the
formation of ferryl intermediates that enables them to oxidise synthetic dye
molecules that are widely used in the textile industry. We have investigated the
catalytic cycle of a dye decolourising peroxidase (DtpA) from a
biotechnologically important bacterium Streptomyces lividans. Using a combination
of steady-state and stopped-flow kinetic investigations, we have determined the
rate constants for all steps in the catalytic cycle with a range of substrate
molecules. For most substrates, the value of kcat/Km measured by steady-state
kinetics is equal to the slowest step in catalysis measured by stopped-flow
spectroscopy, namely the decay of the ferryl FeIV[double bond, length as m-dash]O
species (compound II) to form the ferric species. With the anthraquinone-based
dye, reactive blue 19 (RB19) unusual steady-state kinetic behaviour is observed,
which we propose through kinetic modelling of the catalytic cycle is due to a
disproportionation mechanism of the dye. At low RB19 concentrations, the rate of
disproportionation is slower than that of the rate determining step in DtpA,
whereas at higher concentrations of RB19 the rate of disproportionation is
faster. This mechanism obviates the need to postulate secondary sites for
substrate binding on the enzyme which has been previously proposed for other dye
decolourising haem peroxidases.
PMID- 28695934
TI - Synthetic methodologies and spatial organization of metal chelate dendrimers and
star and hyperbranched polymers.
AB - The synthetic methodologies, physico-chemical peculiarities, properties, and
structure of metal chelate dendrimers and star and hyperbranched polymers are
considered. These compounds are subdivided into molecular, intracomplex, and
macrocyclic types which in turn are classified depending on the nature of the
donor atoms (N,N-, N,O-, N,S-, O,O-, O,S-, S,S-, P,P-chelates, etc.). Special
attention is paid to the features of the preparation of metal chelate star
polymers by "arm-first", "core-first" and click-to-chelate approaches. The main
data on the synthesis, spatial structure and properties of the metal chelate
hyperbranched polymers are summarized. The basic concepts and synthetic
strategies leading to the different types of supramolecular metal chelate
dendrimers are analyzed. The problems and future prospects of metal chelate
dendrimers and star and hyperbranched polymers are outlined. The bibliography
includes papers published after 2010.
PMID- 28695935
TI - High coverage water adsorption on CuO(011) surface.
AB - Spin-polarized density functional theory calculations (GGA+U) and atomic
thermodynamics have been used to study the adsorption of water on the CuO(011)
surface at different coverages. It was found that H2O molecular adsorption on
CuO(011) surface is energetically favorable for one H2O molecule, but
dissociative adsorption is preferred for two and three molecules, while a mixed
molecular and dissociative coadsorption is favorable for four water molecules.
The phase diagram of water adsorption on the CuO(011) surface shows that the
adsorption of three and four water molecules is favorable thermodynamically.
Different single-water adsorption states were analyzed by the Boltzmann model at
different temperatures. The adsorption energy is contributed to by the surface
uncoordinated copper and oxygen atoms, and by hydrogen chemical bonding. The
energetic trends are related to the underlying electronic mechanisms.
PMID- 28695936
TI - High-performance photodetectors based on Sb2S3 nanowires: wavelength dependence
and wide temperature range utilization.
AB - Photodetectors which can work at both low and high temperatures are very
important for the development of practical optoelectronic devices. Many studies
have shown that low-dimensional semiconductors have more advantages in
optoelectronic applications than their bulk forms. Here, we report the
preparation of high-quality Sb2S3 nanowires (NWs) by a sulphur-assisted vapour
transport method. The corresponding individual Sb2S3 NW based photodetectors
exhibit good photoresponse in a wide spectral range from about 300 to 800 nm. The
optimal photoresponse values are measured under the illumination of a 638 nm
laser at room temperature: a high current ON/OFF ratio of about 210, a spectral
responsivity of 1152 A W-1, a detectivity of 2 * 1013 Jones, and rise and fall
times of about 37 ms, respectively. More importantly, the temperature dependence
of the electrical conductivity of Sb2S3 shows three variation regions which can
be attributed to the interaction between the carrier mobility and carrier
concentration. The temperature dependence of the photoresponse of the
photodetectors shows that they have good adaptability to temperature, and they
worked very well at a wide temperature range from 8 to 420 K. Our results
indicate that low-dimensional Sb2S3 crystals are promising candidates for new
multifunctional optoelectronic devices.
PMID- 28695938
TI - Influence of intramolecular vs. intermolecular phosphonium-borohydrides in
catalytic hydrogen, hydride, and proton transfer reactions.
AB - In this computational study, the thermodynamics of hydrogen, hydride, and proton
transfer from 22 phosphonium-borohydride intramolecular and intermolecular
frustrated Lewis pairs (FLPs) to eight probe substrates was investigated. The
purpose of this study was to gain insight into the thermodynamics of H2 transfer
with intramolecular phosphonium-borohydrides; to determine whether intramolecular
or intermolecular FLPs are preferred in FLP-catalyzed hydrogenation reactions.
Comparison of the computed thermodynamic values showed that by connecting a
borohydride and phosphonium center through a linker, H2 loss from the respective
intramolecular phosphonium-borohydride became less favorable by about five and
seven kcal mol-1 in acetonitrile and toluene, respectively. Connecting the
borohydride and phosphonium centers also resulted in both hydride and proton loss
becoming less favorable, on average, by about 10.0 kcal mol-1 and about 4.6 pKa
units, respectively. Analysis of hydrogen, proton, and hydride transfer to eight
probe substrates showed that initial proton transfer is 49 and 20 kcal mol-1 more
favorable than the initial hydride transfer in the reduction of nitrogen
containing and oxygen-containing unsaturated substrates, respectively. These
results suggest that proton transfer, followed by hydride transfer occurs in the
reduction of imines, ketones, aldehydes, and enamines. From the thermodynamic
analysis of proton and hydride transfer, an intramolecular phosphonium
borohydride was the desired catalyst for the reduction of imines and enamines,
while an intermolecular phosphonium-borohydride was the favored catalyst for the
reduction of ketones and aldehydes.
PMID- 28695939
TI - The structural and electronic properties of reduced amorphous titania.
AB - Crystalline titania has been extensively studied using experimental and
theoretical tools. Amorphous titania, however, has received less attention in the
literature, despite its importance for a number of applications, such as
photocatalysis, batteries, and electronic devices. In this work we modeled
amorphous titania using a combination of molecular dynamics and density
functional theory with several stoichiometries (TiOx, 2 >= x >= 1.75). Our
results show that oxygen atom removal from amorphous titania is much easier than
from crystalline titania, indicating that reduced amorphous structures are likely
common. Ti atoms in amorphous titania exhibit a distribution of coordination
numbers (five to seven), but the average coordination number of oxygen increases
upon reduction. We also identified that gap states arise in substoichiometric
titania due to the formation of Ti3+ centers. Such gap states are highly
localized and randomly distributed across different Ti atoms, although we do
observe a slight preference for electron localization on seven-coordinated Ti
atoms. We observe that band gaps increase with reduction of amorphous titania. We
also analyzed a proposed hole hopping mechanism involving oxygen vacancies by
calculating hole hopping distances. We found that such distances are large except
in very reduced states, indicating likely slow hole diffusion through an oxygen
vacancy mechanism. Our work is the first of its kind to thoroughly characterize
the structural and electronic properties of amorphous titania in reduced states.
PMID- 28695940
TI - Self-assembly of MoO3 needles in gas current for cubic formation pathway.
AB - Nucleation and subsequent rapid growth are enigmatic due to the unrevealed
pathways. Despite the relatively simpler mechanism compared to nucleation and
growth in solution, that in vapor has received little attention. The largest
hindrance to unveiling this process may be observing the rapid and mesoscopic
scale phenomena. To overcome this hindrance, we combine an experimental approach
with in situ spatial scanning Fourier-transform infrared spectroscopy, which
reveals the nucleating and growing nanoparticles in vapor. The nanoparticles are
then collected at different evolutionary stages and analyzed by ex situ
transmission electron microscopy (TEM). Needle-shaped molybdenum oxide (MoO3)
nanoparticles were formed within ~0.1 s after homogeneous nucleation from a
highly supersaturated vapor. Over one second, the needle particles gradually
evolved into a cubic shape by fusion in a crystallographically favored
orientation in a free-flying state in vapor. The similar sizes of the elongated
axes of the needle and cubic structures suggest an additional growth stage, in
which the needle particles become the growth units of the cubic particles. The
morphology of a final crystal should reflect the formation environment of the
particle because growing crystals are sensitive to the formation conditions such
as temperature, concentration, and impurities. Although nucleation under very
high supersaturation induces the anisotropic growth of the needle particles, this
information of the initial nucleation environment is lost in the final cubic
crystal. These findings enrich our understanding of pathways in the nucleation
and growth of nanoparticles and provide new insights into the growth stages
driven by oriented attachment.
PMID- 28695942
TI - Gold-silver alloy semi-nanoshell arrays for label-free plasmonic biosensors.
AB - Nanosphere lithography coupled with reactive ion etching has been used to
synthesize hexagonal ordered arrays of Au-Ag bimetallic semi-nanoshells to be
used as plasmonic biosensors. The degree of lateral interaction between adjacent
semi-nanoshells can be controlled by tailoring the reactive ion etching time in
order to boost the global plasmonic properties through the formation of near
field hot-spots, which in turn can improve the sensitivity of the biosensors. To
test the efficiency of the proposed system as a biosensor, we used an established
protocol for the detection of biomolecules (local sensitivity), based on the
receptor-ligand approach and using the biotin-streptavidin model system. We also
tested the sensitivity to a homogeneous change in the refractive index of the
buffer over the sensor (bulk sensitivity). Comparing the obtained results to
those of an array of nanoprisms, chosen as a benchmark, significantly higher
performances both in local and bulk sensitivities have been found, in agreement
with electrodynamics simulations based on finite-element methods.
PMID- 28695943
TI - Copper-catalyzed synthesis of indolyl diketones via C-H oxidation/diacylation of
indoles with arylglyoxal hydrates.
AB - An expedient protocol for Cu-catalyzed C-H oxidation/diacylation of indoles with
arylglyoxal hydrates to construct indolyl diketones is developed. This
methodology exhibits the synthetic utility of the synthesis of an indole-alkaloid
1,2-di(1H-indol-3-yl)ethane-1,2-dione and offers a straightforward means to
produce different indolyl nitrogen-containing heterocycles such as indolyl
quinoxaline, indolyl hydantoin and indolyl imidazole in high yields. Preliminary
mechanistic studies indicate that two proposed pathways are involved in this
process.
PMID- 28695944
TI - Design and modeling of electrode networks for code-division multiplexed resistive
pulse sensing in microfluidic devices.
AB - A typical microfluidic device sorts, captures or fractionates sample constituents
by exposing them to discriminating microenvironments. Direct electronic
acquisition of such manipulation by a network of integrated sensors can provide a
fast, integrated readout, replacing otherwise required microscopy. We have
recently introduced a sensor technology, Microfluidic CODES, which allows us to
multiplex resistive pulse sensors on a microfluidic device. Microfluidic CODES
employs a network of micromachined coplanar electrodes such that particles
passing over these electrodes produce distinguishable code sequences. In this
paper, we explain the design process to specifically generate an orthogonal
digital code set for an efficient and accurate demultiplexing of the sensor
signals. We also introduce an equivalent circuit model for a network of code
multiplexed resistive pulse sensors by utilizing the Foster-Schwan model and
conformal mapping, to model dynamic cell-electrode interaction in a non-uniform
electric field. Our results closely match with both experimental measurements
using cell lines and finite element analysis. The coding and modeling framework
presented here will enable the design of code-division multiplexed resistive
pulse sensors optimized to produce desired waveform patterns to ensure reliable
and efficient decoding.
PMID- 28695945
TI - Enhancement of the lithium ion conductivity of Ta-doped Li7La3Zr2O12 by
incorporation of calcium.
AB - Fast ion conducting garnet materials have been identified as promising
electrolytes for all solid-state batteries. However, reliable synthetic routes to
materials with fully elucidated cation site occupancies where an enhancement in
lithium conductivity is observed remains a challenge. Ca-Incorporation is
developed here as a promising approach to enhance the ionic conductivity of
garnet-type Li7-xLa3Zr2-xTaxO12 phases. Here we present a new sol-gel synthetic
strategy as a facile route to the preparation of materials of a desired
stoichiometry optimized for Li+ conductivity. We have found that the ionic
conductivity of Li6.4La3Zr1.4Ta0.6O12 is increased by a factor of four by the
addition of 0.2 mol of Ca per formula unit. Ca is incorporated in the garnet
lattice where it has no effect on the sinterability of the material and is
predominately located at the La sites. We anticipate that the ease of our
synthetic route and the phases presented here represents a starting point for the
further realization of solid state electrolyte compositions with similarly high
Li+ conductivities using this methodology.
PMID- 28695949
TI - Synthesis and biological evaluation of the ascidian blood-pigment halocyamine A.
AB - Synthesis of the antimicrobial marine natural product halocyamine A has been
achieved utilizing a combination of Sonogashira coupling, ruthenium
complex/ytterbium triflate catalyzed hydroamidation and solid-phase peptide
synthesis (SPPS) chemistry. The synthetic natural product exhibited only modest
levels of antibacterial activities but significant antioxidant activity.
PMID- 28695953
TI - Triaminoborane-bridged diphosphine complexes with Ni and Pd: coordination
chemistry, structures, and ligand-centered reactivity.
AB - The synthesis, coordination chemistry, and reactivity of two diphosphines
containing the cyclic triaminoborane 1,8,10,9-triazaboradecalin (TBD) are
described. To evaluate the ligand-centered reactivity of PhTBDPhos and
iPrTBDPhos, the complexes (PhTBDPhos)MCl2 and (iPrTBDPhos)MCl2, where M = Ni and
Pd, were prepared and characterized by elemental analysis, multinuclear NMR
spectroscopy (1H, 13C, 31P, and 11B), and single-crystal X-ray diffraction (XRD).
Despite very low boron Lewis acidity in the TBD backbone, (PhTBDPhos)NiCl2 (1)
and (PhTBDPhos)PdCl2 (3) react with H2O, alcohols, and hydrated fluoride reagents
in the presence of NEt3 to yield trans H-O or H-F addition across the bridgehead
N-B bond. In contrast, iPrTBDPhos shows no appreciable reactivity when bound to
NiCl2 (2) and PdCl2 (4), which is attributed to the sterically-bulky isopropyl
substituents blocking substrate access to boron in the TBD backbone. The new
complexes {[(PhTBDPhos-H2O)Ni]2(MU-OH)2}Cl2 (5), {[(PhTBDPhos-H2O)Pd]2(MU
OH)2}Cl2 (6), (PhTBDPhos-MeOH)NiCl2 (7), (PhTBDPhos-MeOH)PdCl2 (8), (PhTBDPhos
C3H5OH)PdCl2 (9), and {[(PhTBDPhos-HF)Ni]2(MU-OH)2}Cl2 (10) were isolated, and
all but 6 were structurally characterized by single-crystal XRD. Multinuclear NMR
studies revealed that isolated, crystallographically-authenticated samples of 5-9
lose ligand-bound water or alcohol with reappearance of starting materials 1 and
3 when dissolved in NMR solvents. Addition of NEt3 attenuated the water and
alcohol loss from 5-9 to allow 1H, 13C, 31P, and 11B NMR data to be collected for
all the compounds, confirming the determined structures. Additional reactivity
experiments with NaOMe and fluoride reagents suggested that participation of the
bridgehead nitrogen in the TBD backbone is important for promoting reactivity at
boron when PhTBDPhos is bound to Ni and Pd. The term "cooperative ligand-centered
reactivity" (CLR) is proposed to define chemical reactions that appear to require
participation of more than one atom on the ligand, such as those reported here.
PMID- 28695954
TI - Methodological rigour in the study of addictions.
AB - Editorial of vol 29-3.
PMID- 28695955
TI - States of G0 and the proliferation-quiescence decision in cells, tissues and
during development.
AB - While cellular proliferation is fundamental to the development of all
multicellular organisms, the slowing or stopping of proliferation at the right
places and times is equally important for proper tissue and organ development.
The non-cycling state of cellular quiescence or "G0" is relatively understudied
compared to proliferation, given its prevalence in nature. It may seem that
actively proliferating cells undergo a series of dynamic events, while quiescent
cells are in a passive, static state. However, studies over the last 10-15 years
suggest that quiescence may be more dynamic than previously thought and must also
be actively regulated and maintained. This review focuses on recent advances in
understanding quiescence or G0 and in particular, on observations about the
proliferation-quiescence decision in cell lines, in tissues and during
development. We also discuss novel, advanced molecular tools that are likely to
enable the field to address outstanding, unresolved questions about cellular
quiescence and its regulation.
PMID- 28695956
TI - Regulation of body size in Caenorhabditis elegans: effects of environmental
factors and the nervous system.
AB - Body size is one of the basic traits of animals and is regulated to adapt to the
environment. Animals perceive environmental stimuli with sensory neurons, and
signals from the nervous system alter the size of organs, thus regulating body
size. The model animal Caenorhabditis elegans is particularly suited for genetic
analysis of body size regulation, and has already contributed to the elucidation
of various genetic pathways that regulate body size. In this review, we summarize
the available literature regarding environmental factors that regulate body size
and the role of the nervous system in such regulation. We discuss in detail a
recent report on body size regulation by the neurotransmitter, dopamine.
PMID- 28695957
TI - Interactions among gibberellins, brassinosteroids and genes regulate stomatal
development in the Arabidopsis hypocotyl.
AB - Stomata are pores on the plant surface that enable gas exchange with the
atmosphere. In Arabidopsis thaliana, brassinosteroids, which function upstream of
the TTG/bHLHs/MYBs/GL2 transcriptional network, positively regulate stomatal
formation in the hypocotyl. Gibberellins also promote stomatal development in the
embryonic stem. Here, we investigated the hypothetical interactions between the
gibberellin and brassinosteroid signaling pathways during stomatal formation. By
combining genetics and gene expression studies, we found that gibberellins
promote stomatal development, functioning upstream of both brassinosteroids and
the TTG/bHLHs/MYBs/GL2 network. Gibberellins also regulate an earlier step in
stomatal development than that regulated by the receptor-like membrane protein
TOO MANY MOUTHS.
PMID- 28695958
TI - Identification and characterization of the autophagy-related genes Atg12 and Atg5
in hydra.
AB - Autophagy is an evolutionarily conserved process in eukaryotic cells that is
involved in the degradation of cytoplasmic contents including organelles via the
lysosome. Hydra is an early metazoan which exhibits simple tissue grade
organization, a primitive nervous system, and is one of the classical non
bilaterian models extensively used in evo-devo research. Here, we describe the
characterization of two core autophagy genes, Atg12 and Atg5, from hydra. In
silico analyses including sequence similarity, domain analysis, and phylogenetic
analysis demonstrate the conservation of these genes across eukaryotes. The
predicted 3D structure of hydra Atg12 showed very little variance when compared
to human Atg12 and yeast Atg12, whereas the hydra Atg5 predicted 3D structure was
found to be variable, when compared with its human and yeast homologs.
Strikingly, whole mount in situ hybridization showed high expression of Atg12
transcripts specifically in nematoblasts, whereas Atg5 transcripts were found to
be expressed strongly in budding region and growing buds. This study may provide
a framework to understand the evolution of autophagy networks in higher
eukaryotes.
PMID- 28695959
TI - Migration behavior of PGCs and asymmetrical gonad formation in pond smelt
Hypomesus nipponensis.
AB - In teleost fish, the gonad originates from primordial germ cells (PGCs) and
somatic cells. However, it is not clear whether the final gonadal position is
determined by anteroposterior and dextrosinistral differentiation of endodermal
organs or by the distribution of PGCs. The pond smelt has a transparent body even
after hatching, enabling clear observation of PGC distribution and endodermal
differentiation. Here, we first examined normal embryonic development to define
the spatio-temporal characteristics of our developmental model. Second, the
origin of PGCs was investigated by in situ hybridization. Third, the migration
route of PGCs was tracked by microinjection of GFP-nos3 3' UTR mRNA and
visualization of PGCs by green fluorescent protein. Lastly, differentiation of
gonadal and endodermal organs was examined histologically. Maternal vasa
transcripts were detected at the ends of cleavage furrows, indicating that PGCs
differentiated by inheritance of germplasm as in other teleosts. During
gastrulation, PGCs migrated following somatic cell movement and lined both sides
of the embryonic body. During the segmentation period, PGCs moved posteriorly and
were distributed in a line among dorsal mesentery cells around the posterior part
of the intestinal bulb in the 16th to 24th somite region at 3 days post hatching.
At 1 month post hatching, the gonad was formed at the 20th somite region. PGC
distribution was biased to the left side of the body cavity, while the pancreas
was formed on the right side. These results indicate that PGCs accumulate at the
gonadal region by dorsal mesentery cells, and gonadal position is determined by
the digestive system.
PMID- 28695960
TI - Galectin-1 enhances the generation of neural crest cells.
AB - Neural crest (NC) cells are multipotent cells that emerge from the dorsal region
of the neural tube. After delaminating from the neural tube, NC cells migrate
throughout the developing embryo and differentiate into various cells: neurons
and glial cells of the peripheral nervous system, melanocytes of skin, and
skeletal elements of the face and head. We previously analyzed the gene
expression profile of a NC subpopulation isolated from Sox10-IRES-Venus mice and
found that the carbohydrate-binding protein, Galectin-1 (Gal-1) was strongly
expressed in generating NC cells. In the present study, we identified GAL-1 as a
factor that promotes NC cell generation. Gal-1 was significantly expressed in NC
cells generated in explanted neural tubes. The presence of GAL-1 enhanced the
generation of NC-like cells from mouse embryonic stem (ES) cells. In the
differentiation of ES cells into NC-like cells, GAL-1 enhanced neurogenesis in
the early stages and facilitated NC-like cell generation in the later stages. GAL
1 also enhanced the generation of NC cells from explanted neural tubes. These
results suggest that GAL-1 plays a facilitative role in NC cell generation.
PMID- 28695961
TI - Apolipoprotein C-I mediates Wnt/Ctnnb1 signaling during neural border formation
and is required for neural crest development.
AB - In vertebrates, the neural crest and placodes originate in the neural border,
which is located between the neural plate and epidermal ectoderm. The neural
crest and placodes give rise to a vast array of cell types. Formation of neural
crest is a multi-step process, in which Wnt signals are used reiteratively, but
it is currently not clear if a Wnt signal is required for neural border
formation. Here, we have identified apolipoprotein C-I (apoc1) in a screen for
genes regulated by Wnt/Ctnnb1 signaling in late blastula stage Xenopus tropicalis
embryos. We show that Xenopus laevis apoc1 encodes a small, secreted protein, and
is induced by Wnt/Ctnnb1 signaling. Depletion of Apoc1 protein results in a
neural border formation defect and loss of border fates, including neural crest
cells. However, unlike another Wnt/Ctnnb1 target, gbx2.2, apoc1 is not required
for patterning of the neural border. We further show that gbx2.2 and apoc1 are
independently regulated by Wnt signaling. Our results thus suggest that Wnt
regulates border formation and patterning by distinct genetic mechanisms.
PMID- 28695962
TI - Gdf11/Smad signalling and Cdx proteins cooperate to activate the Hoxc8 early
enhancer in HepG2 cells.
AB - Developing anatomy along the head-tail axis of bilaterian embryos is specified,
to a large extent, by the overlapping patterns of expression of the Hox genes.
Hox gene enhancers respond to a variety of signals in order to regulate these
discreet domains of expression. For mouse Hoxc8, the 399bp "early enhancer" plays
a major role. Activation of this enhancer is now examined using luciferase
expression constructs transfected into HepG2 cells. Constructs are activated by
the combined actions of Gdf11/Smad and Cdx protein signalling pathways, both of
which are functional in early embryos. Each of these pathways alone has little
stimulatory effect. Stimulation by the two pathways together exceeds the sum of
the effects of each pathway alone, indicating synergistic activity. By mutation
analysis, two Smad binding motifs are identified as mediators of the Gdf11 effect
and two Cdx binding motifs mediate the Cdx effect. The two Smad motifs and one of
the Cdx sites are conserved from fish to mammals. Gdf11 stimulation is partially
inhibited by Specific Inhibitor of Smad3, suggesting that Smad3 plays a part in
signal transduction. Fgf2 increases luciferase activation by the Hoxc8 enhancer,
but not, apparently, by specific interactions with either Gdf11 or Cdx effects.
PMID- 28695963
TI - Differential regulation of cumulus cell transcription during oocyte maturation in
vivo and in vitro.
AB - Differences in cumulus cell gene expression after oocyte maturation in vitro
(IVM) or in vivo have been described in previous studies. However, the possible
impact of follicle stage on gene expression deregulation during human oocyte IVM
remains unknown. Expression of selected genes of interest was compared in cumulus
cell of three classes of human cumulus cell-oocyte complexes (COCs): a) COCs
derived from human chorionic gonadotropin (hCG)-triggered IVM cycles, collected
at the germinal vesicle (GV) stage from mid-sized follicles (4-12 mm) and matured
in vitro (IVM-GV); b) COCs derived from hCG-triggered IVM cycles, collected from
mid-sized follicles (4-12 mm) and matured in vivo (IVM-MII); c) COCs derived from
controlled ovarian stimulation in vitro fertilization (IVF) cycles, collected
from large/preovulatory follicles and matured in vivo (IVF-MII). Overall, mRNA
levels of the large majority of the 20 genes of different regulative and
metabolic pathways subject to analysis were altered in IVM samples compared with
in vivo matured COCs. In some cases, follicle size appeared to have a role in
determining transcription deregulation. For example, in comparison to the IVF-MII
control, the luteinizing hormone receptor was largely overexpressed in both IVM
GV and IVM-MII COCs, therefore irrespective of IVM. However, in other
circumstances follicle size and IVM had distinct and opposite impacts on gene
expression, as shown by transcription of amphiregulin, which was increased in IVM
MII COCs, but decreased in COCs matured in vitro (IVM-GV) compared with the IVF
MII control. This study confirms and extends previous data on gene expression
dysregulation during IVM and indicates that the size of follicles from which
immature oocytes are retrieved can be an independent factor of differential
transcriptional regulation.
PMID- 28695964
TI - Segmentation gene expression patterns in Bactrocera dorsalis and related insects:
regulation and shape of blastoderm and larval cuticle.
AB - The oriental fruit fly, Bactrocera dorsalis, is regarded as a severe pest of
fruit production in Asia. Despite its economic importance, only limited
information regarding the molecular and developmental biology of this insect is
known to date. We provide a detailed analysis of B. dorsalis embryology, as well
as the expression patterns of a number of segmentation genes known to act during
patterning of Drosophila and compare these to the patterns of other insect
families. An anterior shift of the expression of gap genes was detected when
compared to Drosophila. This shift was largely restored during the step where the
gap genes control expression of the pair-rule genes. We analyzed and compared the
shapes of the embryos of insects of different families, B. dorsalis and the blow
fly Lucilia sericata with that of the well-characterized Drosophila melanogaster.
We found distinct shapes as well as differences in the ratios of the length of
the anterior-posterior axis and the dorsal-ventral axis. These features were
integrated into a profile of how the expression patterns of the gap gene Kruppel
and the pair-rule gene even-skipped were observed along the A-P axis in three
insects families. Since significant differences were observed, we discuss how
Kruppel controls the even-skipped stripes. Furthermore, we discuss how the
position and angles of the segmentation gene stripes differed from other insects.
Finally, we analyzed the outcome of the expression patterns of the late acting
segment polarity genes in relation to the anlagen of the naked-cuticle and
denticle belt area of the B. dorsalis larva.
PMID- 28695965
TI - Role of Mad2 expression during the early development of the sea urchin.
AB - Mitotic arrest deficient 2 (Mad2) belongs to the spindle assembly checkpoint
(SAC), a mechanism that blocks progression of the cell cycle until microtubule
attachment to kinetochores is complete. It has been found to be involved in the
resistance of cancer cells to "anti-mitotic" drugs such as paclitaxel. Mad2
controls meiotic progression, but its role during sea urchin development had
never been investigated. Furthermore, the existence of a SAC in this species had
never been proved. The present data show that a Mad2 protein, highly homologous
to that of humans, is expressed in this species. Mad2 expression increases during
development, becoming confined to the endomesoderm at gastrula stages. The level
of Mad2 expression is enhanced in embryos that do not gastrulate after treatment
with anti-mitotic drugs, lithium or inhibition of the ERK pathway. Mis-aligned
and lagging chromosomes were induced after injection of an anti-Mad2 antibody or
a Mad2 morpholino. Our results point to the role of a non-canonical SAC involving
Mad2 in the control of mitotic divisions of the sea urchin embryo.
PMID- 28695966
TI - DYRK2 displays muscle fiber type specific function during zebrafish early
somitogenesis.
AB - Dual specificity tyrosine-phosphorylation regulated kinase 2 (DYRK2) is a
serine/threonine kinase. In zebrafish, DYRK2 is expressed in the lateral somites
and adaxial cells at the early stage of embryo development. However, its role in
early myogenesis had not been elucidated yet. Here, we report that DYRK2 mRNA and
MyoD mRNA were colocalized in the muscle progenitor cells in somites, including
both the posterior compartment of the lateral somites and adaxial cells.
Knockdown of DYRK2 reduced the levels of MyoD transcripts in the muscle
progenitor cells in somites. In contrast, overexpression of DYRK2 increased the
levels of MyoD transcripts in the muscle progenitor cells in somites. The effects
of knockdown and overexpression of DYRK2 on the expression of MyoD in the
posterior compartment of the lateral somites were much greater than in the
adaxial cells. Further studies indicated that forced expression of DYRK2
increased the levels of fast-twitch skeletal myosin RNA. Moreover, knockdown or
forced expression of DYRK2 affected the levels of fast-twitch skeletal myosin
protein. Together, these data indicate that DYRK2 is expressed in the developing
muscle progenitor cells in somites and that it positively regulates fast-twitch
muscle differentiation, at least at the early stages.
PMID- 28695967
TI - Expression of the ALK1 family of type I BMP/ADMP receptors during gastrula stages
in Xenopus embryos.
AB - Multiple members of the transforming growth factor beta (TGFbeta) family of
secreted factors play central inductive and patterning roles during
embryogenesis. During gastrulation in vertebrates, the bone morphogenetic protein
(BMP) sub-family is linked to formation of the embryonic organizer, Spemann's
organizer in Xenopus, and dorsal-ventral mesoderm patterning. Our knowledge
regarding the BMP receptors mediating this signaling is still very incomplete.
The BMPR1A (ALK3) and BMPR1B (ALK6) receptors are known to mediate the BMP4
signal. These receptors belong to the ALK1 subfamily of type I receptors that
also includes ACVR1 (ALK2), and ACVRL1 (ALK1). We studied by qPCR and in situ
hybridization the spatio-temporal expression patterns of ALK2 and ALK1 and
compared them to ALK3 and ALK6, and to the main BMPs expressed during
gastrulation, i.e., BMP4, BMP7, BMP2, and ADMP, in an attempt to establish a link
between ligands and receptors. There is extensive overlap between BMP4, and ALk3
and Alk6 expression, supporting their functional interaction. Robust Alk6
expression was observed from mid-gastrula. Animal region expression of both
receptors shows co-expression with BMP4 and BMP7. Alk2 transcripts were detected
within the organizer, overlapping with its proposed ligand, ADMP, suggesting a
probable function within the organizer. Alk1 is very weakly expressed during
gastrula, but its transcripts were localized to the lateral marginal zone
flanking the organizer domain. No receptor closely matched the maternal BMP2
expression, although Alk2, Alk3, and Alk6, have transcripts of maternal origin.
Our analysis shows that the BMP ligands and their receptors exhibit dynamic
expression patterns during gastrula stages.
PMID- 28695968
TI - Robotic-Assisted Radical Prostatectomy with the Use of Barbed Sutures.
AB - OBJECTIVES: The aim of this study is to analyze the principal advantages of
posterior muscolo-fascial reconstruction using knotless barbed sutures (BS)
during robot-assisted radical prostatectomy (RARP). MATERIALS AND METHODS: We
analyzed the available evidence regarding the efficacy and safety of principal BS
(Quill? SRS Angiotech Pharmaceuticals Inc., Vancouver, Canada; V-Loc? Medtronic,
Dublin, Ireland; STRATAFIX? Ethicon Inc., Somerville, New Jersey; Filbloc(r)
Assut Europe S.p.A., Rome, Italy). RESULTS: We analysed the principal outcomes
(operative time and suturing time of urethra-vesical anastomosis, length of
catheterization, hospital stay, and postoperative complications rate) reported in
literature. CONCLUSIONS: In light of our experience, we believe that the
utilization of BS during RARP is safe as the development of a new surgical
technique of urethrovesical anastomosis offers advantages in terms of continence
rate, length of catheterization, and other surgical outcomes. Other studies
(prospective trials) are necessary to investigate the real benefits of BS in
comparison to conventional sutures (CS).
PMID- 28695969
TI - What Influences How Patients Rate Their Hospital Stay After Total Hip
Arthroplasty?
AB - PURPOSE: Measuring the effect of operative interventions has been a challenge in
orthopaedics. The assessment of patient satisfaction, as measured by the Press
Ganey (PG) satisfaction surveys, has gained increasing attention. Our purpose was
to determine the factors and patient characteristics that influence patient
satisfaction after THA. MATERIALS AND METHODS: The PG database was queried
identifying 692 THA patients (November 2009 to January 2015). A multiple
regression analysis was conducted. RESULTS: Significant influence was found in
communication with nurses (p=<0.001), response time of hospital staff (p=0.001),
communication with physicians (p=0.002), and hospital environment (p=0.049).
Management of pain and communication about medications were not significant for
overall hospital rating. There were no differences between PG scores of patients
who did and did not have complications. CONCLUSIONS: Hospital rating was
significantly influenced by patients' communication with nurses, response time of
hospital staff, and communication with physicians. Recognizing the importance of
these elements, can greatly improve patient satisfaction after THA.
PMID- 28695970
TI - Web-Based Video Assessments of Operative Performance for Remote Telementoring.
AB - INTRODUCTION: Performance-based feedback is critical to surgical skills
acquisition. Barriers of geography and time limit trainees' access to expert
mentorship. In this study, we hypothesized that telementoring using an
asynchronous, web-based video interface would allow trainees to receive
systematic feedback from expert mentors despite these barriers. MATERIALS AND
METHODS: Between October 2014 and October 2016, 18 surgeons in Brazil, Dominican
Republic, Haiti, and Paraguay underwent in-person training in Lichtenstein for
hernioplasty or laparoscopic total extraperitoneal inguinal hernia repair. After
initial training, surgeons submitted 6- to 12-month interval operative videos for
expert review. Expert surgeons reviewed each video using the Surgus web platform
with performance metrics adapted from the Operative Performance Rating Scale
(OPRS). The time required to perform video review, number of freeform comments,
mean OPRS scores, and variance of OPRS scores among telementors was assessed.
RESULTS: A total of 18 surgeons submitted 20 operative videos, and three expert
surgeons reviewed each video using the Surgus platform. The median time to
perform video review was 20 minutes. Median number of freeform verbal comments
was eight. Mean OPRS overall performance scores were 3.9 +/- 0.9 (scale of five).
Mean variance in scoring among telementors for overall performance was 0.25
(maximum 5.29), suggesting a high degree of concordance. CONCLUSIONS: Video-based
assessments had a high degree of concordance among expert raters. Asynchronous
performance reviews by telementors offer opportunities for longitudinal feedback
that overcome geographical, material, and temporal disparities. This platform
offers a means of sharing expertise in surgical training, continuing education,
credentialing, and global health.
PMID- 28695971
TI - Transfusion Requirements Following Total Knee Arthroplasty in Patients with
Preexisting Blood Dyscrasia.
AB - INTRODUCTION: There is a paucity of studies investigating the incidence of
transfusions in various blood dyscrasias after total knee arthroplasty (TKA). The
purpose of this study was: 1) to compare the incidence of transfusion post-TKA in
patients with and without blood dyscrasia; 2) to compare the post-TKA transfusion
incidence of patients with the various individual blood dyscrasias; and 3) to
stratify the findings based on gender and age. MATERIALS AND METHODS: A
retrospective review of a Medicare database for patients with preexisting blood
dyscrasia was conducted. Patients who underwent TKA and had a blood transfusion
were identified by current procedural terminology (CPT) and International
Classification of Diseases (ICD-9) ninth revision codes. We compared the
incidence of transfusion post-TKA in patients with and without blood dyscrasia as
well as transfusion incidence for various individual blood dyscrasias. We
stratified these findings based on gender and age of the patients. RESULTS: There
was a higher incidence of postoperative transfusion in patients who had a blood
dyscrasia, when compared to those who did not (5.8% vs. 2.7%). The most common
type of blood dyscrasia was iron deficiency anemia (81,897). Patients who had
aplastic anemia had the highest incidence of transfusion (16.9%). Females were
more likely to be anemic (69.1%) compared to males (30.1%); however, the
incidence of transfusion was significantly higher in males (6.9%) compared with
females (5.5%). CONCLUSION: The incidence of transfusion was higher in patients
with blood dyscrasia. In addition, certain types of blood dyscrasias were
associated with higher rates of transfusion. Aplastic anemia had the highest
transfusion rate. There was a higher rate of blood transfusions in men when
compared to women, although women had a higher prevalence of blood dyscrasias.
Future studies need to be conducted to further educate patients and practitioners
and optimize TKA blood management care.
PMID- 28695972
TI - The Incidence of Postoperative Pneumonia in Various Surgical Subspecialties: A
Dual Database Analysis.
AB - INTRODUCTION: Pneumonia is the third most common postoperative complication.
However, its epidemiology varies widely and is often difficult to assess. For a
better understanding, we utilized two national databases to determine the
incidence of postoperative pneumonia after various surgical procedures.
Specifically, we used the American College of Surgeons National Surgical Quality
Improvement Program (ACS NSQIP) and the Nationwide Inpatient Sample (NIS) to
determine the incidence and yearly trends of postoperative pneumonia following
orthopaedic, urologic, otorhinolaryngologic, cardiothoracic, neurosurgery, and
general surgeries. MATERIALS AND METHODS: The NIS and NSQIP databases from 2009
2013 were utilized. The Clinical Classification Software (CCS) for International
Classification of Diseases, 9th edition (ICD-9) codes provided by the NIS
database was used to identify all surgical subspecialty procedures. The incidence
of postoperative pneumonia was identified as the total number of cases under each
identifying CCS code that also had ICD-9 codes for postoperative pneumonia. In
the NSQIP database, the surgical subspecialties were selected using the following
identifying string variables provided by NSQIP: 1) "Orthopedics", 2)
"Otolaryngology (ENT)", 3) "Urology", 4) "Neurosurgery", 5) "General Surgery",
and 6) "Cardiac Surgery" and "Thoracic Surgery". Cardiac and thoracic surgery was
merged to create the variable "Cardiothoracic Surgery". Postoperative pneumonia
cases were extracted utilizing the available NSQIP nominal variables. All
variables were used to isolate the incidences of postoperative pneumonia
stratified by surgical specialty. A subsequent trend analysis was conducted to
assess the associations between operative year and incidence of postoperative
pneumonia. RESULTS: For all NIS surgeries, the incidence of postoperative
pneumonia was 0.97% between 2009 and 2013. The incidence was highest among
patients who underwent cardiothoracic surgery (3.3%) and urologic surgery
(1.73%). Patients who underwent general surgery, neurosurgery, spine surgery,
orthopaedic surgery, and ENT surgery had a postoperative pneumonia incidence of
1.1%, 0.6%, 0.5%, 0.5%, and 0.4%, respectively. Overall trend analysis
demonstrated a statistically significant decrease in postoperative pneumonia
incidence (p <0.001), which paralleled in each specialty as well. In NSQIP, the
incidence of postoperative pneumonia for all surgeries that occurred between 2009
and 2013 was 1.3%. The incidences of postoperative pneumonia were highest among
patients who underwent cardiothoracic surgery (5.3%), general surgery (1.4%), and
neurosurgery (1.4%). The incidences of postoperative pneumonia in patients who
underwent ENT surgery, orthopedic surgery, and urologic surgery were 0.7%,
respectively. Overall trend analysis demonstrated a statistically significant
increase in postoperative pneumonia incidence for patients undergoing
cardiothoracic surgery (p <0.001). There were no notable trends for the other
surgical subspecialties. CONCLUSION: The incidence of postoperative pneumonia
differs between the two national databases. Furthermore, the incidences differed
among the various surgical subspecialties; however, cardiothoracic surgery had
the highest incidence in both databases. Furthermore, cardiothoracic surgery
appeared to have an increasing trend in incidence. Standardizing and implementing
accurate coding methodologies for this complication are needed for a more
accurate assessment of this burdensome complication. Future studies should assess
interventions, such as oral cleansing and suctioning, incentive spirometry, as
well as designated institution-based pneumonia prevention programs and protocols
to help prevent and mitigate the occurrence of this complication.
PMID- 28695973
TI - What is the Impact of Body Mass Index on Cardiovascular and Musculoskeletal
Health?
AB - Obesity has become a major public health concern over the past several decades
and has been shown to be associated with type 2 diabetes, cardiovascular
diseases, dyslipidemia, hypertension, osteoarthritis (OA), and certain types of
cancer. The impact of excess weight on cardiovascular and musculoskeletal health
is not well-summarized in the literature, and there are some contradictory
reports. Therefore, the purpose of this study was to assess the impact of body
mass index (BMI) on: 1) cardiovascular outcomes; 2) osteoarthritis risk and
progression; and 3) total knee arthroplasty outcomes (TKA). Three literature
searches were performed to identify clinical studies that assessed how BMI
affects cardiovascular and musculoskeletal health. We included reports published
within last five years. A total of 138 studies on cardiovascular health and 140
studies on musculoskeletal health were identified. After reviewing the abstracts
and related citations from the references, there were 29 studies included in the
present study. The effect of varying levels of BMI have demonstrated a
relationship to cardiovascular disease, osteoarthritis, and TKA outcomes. The
evidence suggests that as BMI increases, the chance of developing cardiovascular
disease, OA, and negative TKA outcomes also increases. Furthermore, there appears
to be a negative effect with being underweight on outcomes as well, suggesting
that being at "normal" weight may optimize outcomes. However, there are several
reports which make these findings more complicated. Several beneficial factors
associated with higher BMI include increased muscle mass and strength, which can
potentially be beneficial through better cardiorespiratory fitness or hormonal
effects. Additionally, several studies suggest that improving fitness is more
important than intentional weight loss for cardiovascular health and
osteoarthritis. Therefore, future studies are warranted to assess the combination
of BMI and activity to assess the optimal balance and how they affect
cardiovascular and musculoskeletal outcomes.
PMID- 28695974
TI - What determines the quality of life of adult patients after Fontan procedure?
AB - BACKGROUND: Despite the low early mortality of Fontan procedures, Fontan patients
are prone to vari-ous cardiac and extra-cardiac complications in the long term.
This may influence patient perception of their health and outcome. The aim of the
study was to assess the relationship of multi-organ compli-cations and physical
efficiency with self-reported health-related quality of life (QOL) in adult
Fontan patients. METHODS: Quality of life was assessed with the Short Form-36
questionnaire. Laboratory tests were done together with echocardiography,
plethysmography, and cardiopulmonary exercise test. RESULTS: The QOL was poorer
in patients than in control subjects. The physical characteristics of patients
correlated with dynamic ventilatory parameters, heart rate at the peak of
exercise, alanine aminotransferase and albumin level. CONCLUSIONS: Liver
impairment and chronotropic incompetence during exercise are associated with poor
QOL in patients after Fontan procedure. In these patient, hepatic, pulmonary and
cardiac functions should be carefully monitored. (Cardiol J 2018; 25, 1: 72-80).
PMID- 28695975
TI - Decreased admissions and hospital costs with a neutral effect on mortality
following lowering of the troponin T cutoff point to the 99th percentile.
AB - BACKGROUND: The implementation of high-sensitivity cardiac troponin T (hs-cTnT)
assays and a cutoff based on the 99th cTnT percentile in the evaluation of
patients with suspected acute coronary syndrome has not been uniform due to
uncertain effects on health benefits and utilization of limited resources.
METHODS: Clinical and laboratory data from patients with chest pain or dyspnea at
the emergency de!partment (ED) were evaluated before (n = 20516) and after (n =
18485) the lowering of the hs-cTnT cutoff point from 40 ng/L to the 99th hs-cTnT
percentile of 14 ng/L in February 2012. Myocardial infarction (MI) was diagnosed
at the discretion of the attending clinicians responsible for the patient.
RESULTS: Following lowering of the hs-cTnT cutoff point fewer ED patients with
chest pain or dyspnea as the principal complaint were analyzed with an hs-cTnT
sample (81% vs. 72%, p < 0.001). Overall 30-day mortality was unaffected but
increased among patients not analyzed with an hs-cTnT sample (5.3% vs. 7.6%, p <
0.001). The MI frequency was unchanged (4.0% vs. 3.9%, p = 0.72) whereas
admission rates decreased (51% vs. 45%, p < 0.001) as well as hospital costs.
Coronary angiographies were used more frequently (2.8% vs. 3.3%, p = 0.004) but
with no corresponding change in coronary interventions. CONCLUSIONS: At the
participating hospital, lowering of the hs-cTnT cutoff point to the 99th
percentile decreased admissions and hospital costs but did not result in any
apparent prognostic or treatment benefits for the patients.
PMID- 28695976
TI - Adaptation of global hemostasis to therapeutic hypothermia in patients with out
of-hospital cardiac arrest: Thromboelastography study.
AB - BACKGROUND: The use of mild therapeutic hypothermia (MTH) in patients after out
of-hospital cardiac arrest (OHCA) who are undergoing primary percutaneous
coronary intervention (pPCI) can protect patients from thromboembolic
complications. The aim of the study was to evaluate the adaptive mechanisms of
the coagulation system in MTH-treated comatose OHCA survivors. METHODS: Twenty
one comatose OHCA survivors with acute coronary syndrome undergoing immediate
pPCI were treated with MTH. Quantitative and qualitative analyses of physical
clot properties were performed using thromboelastography (TEG). Two analysis time
points were proposed: 1) during MTH with in vitro rewarming conditions (37oC) and
2) after restoration of normothermia (NT) under normal (37oC) and in vitro
cooling conditions (32oC). RESULTS: During MTH compared to NT, reaction time (R)
was lengthened, clot kinetic parameter (alpha) was significantly reduced, but no
effect on clot strength (MA) was observed. Finally, the coagulation index (CI)
was significantly reduced with clot fibrinolysis attenuated during MTH. The clot
lysis time (CLT) was shortened, and clot stability (LY60) was lower compared with
those values during NT. In vitro cooling generally influenced clot kinetics and
reduced clot stability after treatment. CONCLUSIONS: Thromboelastography is a
useful method for evaluation of coagulation system dysfunction in OHCA survivors
undergoing MTH. Coagulation impairment in hypothermia was associated with a
reduced rate of clot formation, increased weakness of clot strength, and
disturbances of fibrinolysis. Blood sample analyses performed at 32 degrees C
during MTH, instead of the standard 37 degrees C, seems to enhance the accuracy
of the evaluation of coagulation impairment in hypothermia.
PMID- 28695977
TI - Quality of life in patients with coronary artery disease treated with coronary
artery bypass grafting and hybrid coronary revascularization.
AB - BACKGROUND: Patients with stable coronary artery disease (CAD) have a worse
quality of life (QoL) in comparison to patients without stable CAD. Standardized
questionnaires are used in evaluation of QoL. Hybrid coronary revascularization
(HCR) is a recently-introduced, minimally invasive option for patients requiring
revascularization for coronary lesions. The aim of this study was to assess
healthrelated quality of life (HRQoL) in patients with multivessel CAD (MVCAD),
according to the mode of revascularization: coronary artery bypass grafting
(CABG) or HCR, using the generic SF-36 v.2 questionnaire. METHODS: From November
2009 to July 2012, 200 patients from POLMIDES study with diagnosed MVCAD and were
referred for conventional CABG were randomized to HCR (n = 98) or CABG (n =102)
groups in 1:1 ratio. HRQoL were measured at two time points: hospital admission
and 12-month follow up. The primary endpoint was the difference in HRQoL after
the procedure. RESULTS: Both groups showed the same improvement of HRQoL: in HCR
group: 13.5 (3.82-22.34) vs. CABG group: 10.48 (2.46-31.07); p = 0.76.
CONCLUSIONS: HRQoL in patients after both modes of revascularization
significantly improved after 12 months in all domains.
PMID- 28695978
TI - Ultrasonographic gastric volume before unplanned surgery.
AB - We aimed to measure gastric antral cross-sectional area with ultrasound and
estimate the gastric volume of 300 patients before unplanned surgery, fasted for
at least six hours. Measurements were successfully recorded in 263 semi-recumbent
patients. The median (IQR [range]) area was 333 (241-472 [28-1803]) mm2 and the
mean (SD) estimated volume was 45.8 (34.0) ml. The area exceeded 410 mm2 in
92/263 (35%) measurements. Body mass index and morphine administration were
associated with larger gastric areas on multivariable linear regression analysis,
with beta coefficient (95%CI) 0.02 (0.01-0.04), p = 0.01, 0.23 (0.01-0.46), p =
0.04, respectively. Fasting time was not associated with gastric area and
therefore could not substitute for ultrasound measurements in this cohort.
PMID- 28695979
TI - Withdrawal of treatment after devastating brain injury: post-cardiac arrest
pathways lead in best practice.
PMID- 28695980
TI - Arterial to end-tidal carbon dioxide difference in children undergoing mechanical
ventilation of the lungs during general anaesthesia.
AB - Capnography (ETCO2 ) is routinely used as a non-invasive estimate of arterial
carbon dioxide (PaCO2 ) levels in order to modify ventilatory settings, whereby
it is assumed that there is a positive gap between PaCO2 and ETCO2 of
approximately 0.5 kPa. However, negative values (ETCO2 > PaCO2 ) can be observed.
We retrospectively analysed arterial to end-tidal carbon dioxide differences in
799 children undergoing general anaesthesia with mechanical ventilation of the
lungs in order to elucidate predictors for a negative gap. A total of 2452 blood
gas analysis readings with complete vital sign monitoring, anaesthesia gas
analysis and spirometry data were analysed. Mean arterial to end-tidal carbon
dioxide difference was -0.18 kPa (limits of 95% agreement -1.10 to 0.74) and
71.2% of samples demonstrated negative values. The intercept model revealed PaCO2
to be the strongest predictor for a negative PaCO2 -ETCO2 difference. A decrease
in PaCO2 by 1 kPa resulted in a decrease in the PaCO2 -ETCO2 difference by 0.23
kPa. This study demonstrates that ETCO2 monitoring in children whose lungs are
mechanically ventilated may paradoxically lead to overestimation of ETCO2 (ETCO2
> PaCO2 ) with a subsequent risk of unrecognised hypocarbia.
PMID- 28695981
TI - Monitoring of light chain myeloma - time for a change.
PMID- 28695982
TI - Combinations of genotoxic tests for the evaluation of group 1 IARC carcinogens.
AB - Many of the known human carcinogens are potent genotoxins that are efficiently
detected as carcinogens in human populations but certain types of compounds such
as immunosuppressants, sex hormones, etc. act via non-genotoxic mechanism. The
absence of genotoxicity and the diversity of modes of action of non-genotoxic
carcinogens make predicting their carcinogenic potential extremely challenging.
There is evidence that combinations of different short-term tests provide a
better and efficient prediction of human genotoxic and non-genotoxic carcinogens.
The purpose of this study is to summarize the in vivo and in vitro comet assay
(CMT) results of group 1 carcinogens selected from the International Agency for
Research on Cancer and to discuss the utility of the comet assay along with other
genotoxic assays such as Ames, in vivo micronucleus (MN), and in vivo chromosomal
aberration (CA) test. Of the 62 agents for which valid genotoxic data were
available, 38 of 61 (62.3%) were Ames test positive, 42 of 60 (70%) were in vivo
MN test positive and 36 of 45 (80%) were positive for the in vivo CA test. Higher
sensitivity was seen in in vivo CMT (90%) and in vitro CMT (86.9%) assay.
Combination of two tests has greater sensitivity than individual tests: in vivo
MN + in vivo CA (88.6%); in vivo MN + in vivo CMT (92.5%); and in vivo MN + in
vitro CMT (95.6%). Combinations of in vivo or in vitro CMT with other tests
provided better sensitivity. In vivo CMT in combination with in vivo CA provided
the highest sensitivity (96.7%).
PMID- 28695983
TI - Erythema multiforme triggered by imiquimod 5% cream.
PMID- 28695984
TI - Triptolide prevents extracellular matrix accumulation in experimental diabetic
kidney disease by targeting microRNA-137/Notch1 pathway.
AB - MicroRNAs (miRNAs) are involved in multiple biological functions via suppressing
target genes. Triptolide is a monomeric compound isolated from a traditional
Chinese herb, which exerts protective roles in many kinds of glomerular diseases.
However, our understanding of the triptolide effect on miRNAome is still limited.
In this study, we found that triptolide significantly decreased albuminuria and
improved glomerulosclerosis in rats with diabetic kidney disease (DKD). And
triptolide also inhibited extracellular matrix (ECM) protein accumulation and the
notch1 pathway activation under diabetic conditions. MiR-137 was significantly
decreased in the HG (high glucose)-treated HRMCs and in the kidney tissues of the
diabetic rats, but was upregulated by triptolide. In addition, overexpression of
miR-137 exerted similar effects to those of triptolide, while miR-137 inhibition
aggravated ECM protein accumulation. Luciferase reporter assay results
demonstrated that miR-137 directly targets Notch1. Furthermore, the miR-137
dependent effects were due to Notch1 suppression that in turn inhibited ECM
protein expression, key mediators of glomerulosclerosis. Finally, downregulation
of miR-137 reversed the ECM inhibition role of triptolide in HG cultured HRMCs.
Taken together, these findings indicate that triptolide is a potential
therapeutic option for DKD and that miR-137/Notch1 pathway play roles in the anti
glomerulosclerosis mechanism of triptolide.
PMID- 28695985
TI - Intrastriatal administration of botulinum neurotoxin A normalizes striatal D2 R
binding and reduces striatal D1 R binding in male hemiparkinsonian rats.
AB - Cerebral administration of botulinum neurotoxin A (BoNT-A) has been shown to
improve disease-specific motor behavior in a rat model of Parkinson disease (PD).
Since the dopaminergic system of the basal ganglia fundamentally contributes to
motor function, we investigated the impact of BoNT-A on striatal dopamine
receptor expression using in vitro and in vivo imaging techniques (positron
emission tomography and quantitative autoradiography, respectively). Seventeen
male Wistar rats were unilaterally lesioned with 6-hydroxydopamine (6-OHDA) and
assigned to two treatment groups 7 weeks later: 10 rats were treated
ipsilaterally with an intrastriatal injection of 1 ng BoNT-A, while the others
received vehicle (n = 7). All animals were tested for asymmetric motor behavior
(apomorphine-induced rotations and forelimb usage) and for striatal expression of
dopamine receptors and transporters (D1 R, D2 R, and DAT). The striatal D2 R
availability was also quantified longitudinally (1.5, 3, and 5 months after
intervention) in 5 animals per treatment group. The 6-OHDA lesion alone induced a
unilateral PD-like phenotype and a 13% increase of striatal D2 R. BoNT-A
treatment reduced the asymmetry in both apomorphine-induced rotational behavior
and D2 R expression, with the latter returning to normal values 5 months after
intervention. D1 R expression was significantly reduced, while DAT concentrations
showed no alteration. Independent of the treatment, higher interhemispheric
symmetry in raclopride binding to D2 R was generally associated with reduced
forelimb akinesia. Our findings indicate that striatal BoNT-A treatment
diminishes motor impairment and induces changes in D1 and D2 binding site density
in the 6-OHDA rat model of PD.
PMID- 28695986
TI - Acute heart failure as a result of granulomatous myocarditis: case report on a
patient with metastatic melanoma treated with dabrafenib and trametinib.
PMID- 28695987
TI - Actinic keratoses treated with cold atmospheric plasma.
PMID- 28695988
TI - CREPT and p15RS regulate cell proliferation and cycling in chicken DF-1 cells
through the Wnt/beta-catenin pathway.
AB - The CREPT (cell cycle-related and expression elevated protein in tumor, also
known as RPRD1B) and p15RS (p15INK4b -related sequence, also known as RPRD1A)
have been shown to regulate cell proliferation and alter the cell cycle through
Wnt/beta-catenin pathway downstream genes in human. Although several studies have
revealed the mechanism by which CREPT and p15RS regulate cell proliferation in
human and mammals, it is still unclear how these genes function in poultry. In
order to determine the function of CREPT and p15RS in chicken, we examined the
expression of CREPT and p15RS in a variety of chicken tissues and DF-1 cells.
Then, we determined the effect of overexpression or depletion of CREPT or p15RS,
by transiently transfecting chicken DF-1 cells with overexpression and short
hairpin RNA (shRNA) vectors respectively, on the regulation of cell
proliferation. The results showed that CREPT and p15RS had different expression
patterns and opposite effects on the cell cycling and proliferation. Knockdown of
p15RS expression or overexpression of CREPT facilitated cell proliferation by
promoting the cell-cycle transition from G0/G1 to S-phase and G2/M, whereas
knockdown of CREPT or overexpression of p15RS inhibited cell proliferation.
Mechanistically, CREPT and p15RS control DF-1 cell proliferation by regulating
the expression of Wnt/beta-catenin pathway downstream regulatory genes, including
beta-catenin, TCF4, and Cyclin D1. In conclusion, CREPT and p15RS regulate cell
proliferation and the cell-cycle transition in chicken DF-1 cells by regulating
the transcription of Wnt/beta-catenin pathway downstream regulatory genes.
PMID- 28695989
TI - Efficacy and safety of secukinumab in treating moderate to severe plaque
psoriasis in two real-world Canadian dermatology clinics: a multicenter
retrospective study.
PMID- 28695990
TI - Isocyanurate Formation During Oxazolidinone Synthesis from Epoxides and
Isocyanates Catalysed by a Chromium(Salphen) Complex.
AB - Chromium(salphen) complex 10 is found to be a catalyst for the preparation of
oxazolidinones from epoxides and isocyanates. Using the optimal reaction
conditions (1.5 mol % of chromium(salphen) complex 10 at 80 degrees C in toluene
for 4 hours), six epoxides were reacted with five isocyanates, providing 15
oxazolidinones in up to 90 % yield. With electron-deficient isocyanates,
cyclotrimerisation of the isocyanate to the corresponding isocyanurates is a
competing reaction, showing the importance of matching catalyst activity to that
of the substrates.
PMID- 28695991
TI - Suprascapular artery pseudoaneurysm.
PMID- 28695992
TI - Optimal radiotherapy target volumes in intracranial nongerminomatous germ cell
tumors: Long-term institutional experience with chemotherapy, surgery, and dose-
and field-adapted radiotherapy.
AB - PURPOSE: To evaluate patterns of failure after multimodality treatment of
nongerminomatous germ cell tumors (NGGCTs). MATERIALS AND METHODS: We
retrospectively reviewed records of 34 patients diagnosed with primary
intracranial NGGCT between 1988 and 2014. RESULTS: Thirty-four patients received
induction chemotherapy followed by radiation with or without surgery. Median
follow-up was 11.1 years (0.8-23.3). Outcomes were significantly improved in
these 34 patients (5-year overall survival [OS]: 88% versus 50%, P = 0.0092), so
analysis is restricted to that subset. Disease-free survival (DFS) was 67, 60,
and 54% at 5, 10, and 15 years, respectively. Elevated cerebrospinal fluid-alpha
fetoprotein (CSF-AFP) at diagnosis was associated with poorer DFS (37 vs. 89% at
10 years; P = 0.01). There was no statistically significant difference in OS, or
DFS, or patterns of failure for limited radiotherapy volumes versus larger
volumes; however, patients receiving initial local radiotherapy had 32% distant
central nervous system (CNS) recurrence at 10 years compared to 0% for those
receiving initial larger field irradiation (P = 0.09). Fifteen patients recurred.
All four patients who relapsed in the spine had received local radiotherapy and
had elevated serum and CSF-AFP at baseline. All three patients with ventricular
relapse received local radiation therapy. CONCLUSIONS: NGGCT patients continue to
relapse beyond 5 years. Late ventricular relapse occurred even in patients
without clear evidence of germinoma component. Elevated CSF-AFP at diagnosis is
associated with poor DFS and risk for distant CNS relapse. Patients with residual
radiographic disease after chemotherapy or residual malignant histologies after
second-look surgery have inferior outcomes. Our data support consideration of
treatment intensification for these patients.
PMID- 28695993
TI - Sugammadex: when should we be giving it?
PMID- 28695994
TI - Comparative efficacy of Bentonite clay, activated charcoal and Trichosporon
mycotoxinivorans in regulating the feed-to-tissue transfer of mycotoxins.
AB - BACKGROUND: Mycotoxins contamination in animal products and by-products is a
persistent threat to the food and feed industry. The present study was designed
to evaluate the comparative inhibitory effects of Bentonite (BN), activated
charcoal (AC) and a newly discovered yeast, Trichosporon mycotoxinivorans (TM),
against feed-to-tissue transfer of mycotoxins. RESULTS: A dose dependent increase
as determined by HPLC, in the residues of aflatoxin B1 (AFB1) and ochratoxin A
(OTA) was exhibited in the groups of birds fed AFB1 and OTA alone. The dietary
addition of BN and AC to AFB1-contaminated diets resulted in a 41-87% and 16-72%
decrease in AFB1 residues in liver of the birds, respectively. However, this
decrease was non-significant with addition of TM as AFB1 binder. A partial to non
significant protection was observed by dietary BN and AC, against OTA residues,
while a significant decrease in OTA residues (38-84%) was noted in TM-OTA co-fed
groups. CONCLUSION: The order of efficacy in terms of lowering AFB1 residues in
the liver was BN > AC > TM, while against OTA it was TM > BN > AC. The findings
of present study suggest that, based upon the nature of target mycotoxins, a
mixture of multi-mycotoxins binders/detoxifiers should be incorporated in the
animal feeds. (c) 2017 Society of Chemical Industry.
PMID- 28695995
TI - Cytogenetic findings in WHO-defined polycythaemia vera and their prognostic
relevance.
PMID- 28695996
TI - Down-regulation of genes coding for core RNAi components and disease resistance
proteins via corresponding microRNAs might be correlated with successful Soybean
mosaic virus infection in soybean.
AB - Plants protect themselves from virus infections by several different defence
mechanisms. RNA interference (RNAi) is one prominent antiviral mechanism, which
requires the participation of AGO (Argonaute) and Dicer/DCL (Dicer-like)
proteins. Effector-triggered immunity (ETI) is an antiviral mechanism mediated by
resistance (R) genes, most of which encode nucleotide-binding site-leucine-rich
repeat (NBS-LRR) family proteins. MicroRNAs (miRNAs) play important regulatory
roles in plants, including the regulation of host defences. Soybean mosaic virus
(SMV) is the most common virus in soybean and, in this work, we identified dozens
of SMV-responsive miRNAs by microarray analysis in an SMV-susceptible soybean
line. Amongst the up-regulated miRNAs, miR168a, miR403a, miR162b and miR1515a
predictively regulate the expression of AGO1, AGO2, DCL1 and DCL2, respectively,
and miR1507a, miR1507c and miR482a putatively regulate the expression of several
NBS-LRR family disease resistance genes. The regulation of target gene expression
by these seven miRNAs was validated by both transient expression assays and RNA
ligase-mediated rapid amplification of cDNA ends (RLM-RACE) experiments.
Transcript levels for AGO1, DCL1, DCL2 and five NBS-LRR family genes were
repressed at different time points after SMV infection, whereas the corresponding
miRNA levels were up-regulated at these same time points. Furthermore, inhibition
of miR1507a, miR1507c, miR482a, miR168a and miR1515a by short tandem target mimic
(STTM) technology compromised SMV infection efficiency in soybean. Our results
imply that SMV can counteract soybean defence responses by the down-regulation of
several RNAi pathway genes and NBS-LRR family resistance genes via the induction
of the accumulation of their corresponding miRNA levels.
PMID- 28695997
TI - Reply to comment on: Glucose levels before the onset of asparaginase predicts
transient hyperglycemia in children with acute lymphoblastic leukemia.
PMID- 28695998
TI - Co-surgeons in breast reconstructive microsurgery: What do they bring to the
table?
AB - INTRODUCTION: Current research within other surgical specialties suggests that a
co-surgeon approach may reduce operative times and complications associated with
complex bilateral procedures, possibly leading to improved patient and surgical
outcomes. We sought to evaluate the role of the co-surgery team and its
development in free flap breast reconstruction. METHODS: A retrospective review
of free-flap breast reconstruction by two surgeons from 2011 to 2016 was
conducted. We analyzed 128 patients who underwent bilateral-DIEP breast. Surgical
groups were: single-surgeon reconstruction (SSR; 35 patients), co-surgery where
both surgeons are present for entire reconstruction (CSR-I; 69 patients), and co
surgery reconstruction where co-surgeons appropriately assist in two concurrent
or staggered cases (CSR-II; 24 patients). Efficiency data collected was OR time
and patient length-of-stay (LOS). The rate of flap-failure, return to OR,
infection, wound breakdown, seroma, hematoma, and PE/DVT were compared. RESULTS:
Single-surgeon reconstruction had significantly longer OR time (678 vs. 485 min,
P < .0001), LOS (5 vs. 3.9 days, P < .001), higher wound occurrences of the
umbilical site that required surgical correction [11.4 percent (n = 4) vs. 1.5%
(n = 1); P < .043] compared to CSR-I. Similarly, SSR had significantly longer
average OR time (678 vs. 527 min P < .0001), average LOS (5 vs. 4 days, P =
.0005) when compared with CSR-II. There were no total increased patient related
complications associated with co-surgery (CSR-I or II). CONCLUSION: The addition
of a co-surgeon, even with concurrent surgery, reduces operative time, average
patient LOS, and postoperative complications. This work lends a strong credence
that co-surgery model is associated with increased operative efficiency.
PMID- 28695999
TI - To be certain about the uncertainty: Bayesian statistics for 13 C metabolic flux
analysis.
AB - 13 C Metabolic Fluxes Analysis (13 C MFA) remains to be the most powerful
approach to determine intracellular metabolic reaction rates. Decisions on strain
engineering and experimentation heavily rely upon the certainty with which these
fluxes are estimated. For uncertainty quantification, the vast majority of 13 C
MFA studies relies on confidence intervals from the paradigm of Frequentist
statistics. However, it is well known that the confidence intervals for a given
experimental outcome are not uniquely defined. As a result, confidence intervals
produced by different methods can be different, but nevertheless equally valid.
This is of high relevance to 13 C MFA, since practitioners regularly use three
different approximate approaches for calculating confidence intervals. By means
of a computational study with a realistic model of the central carbon metabolism
of E. coli, we provide strong evidence that confidence intervals used in the
field depend strongly on the technique with which they were calculated and, thus,
their use leads to misinterpretation of the flux uncertainty. In order to provide
a better alternative to confidence intervals in 13 C MFA, we demonstrate that
credible intervals from the paradigm of Bayesian statistics give more reliable
flux uncertainty quantifications which can be readily computed with high accuracy
using Markov chain Monte Carlo. In addition, the widely applied chi-square test,
as a means of testing whether the model reproduces the data, is examined closer.
PMID- 28696000
TI - Systems metabolic engineering as an enabling technology in accomplishing
sustainable development goals.
AB - With pressing issues arising in recent years, the United Nations proposed 17
Sustainable Development Goals (SDGs) as an agenda urging international
cooperations for sustainable development. In this perspective, we examine the
roles of systems metabolic engineering (SysME) and its contribution to improving
the quality of life and protecting our environment, presenting how this field of
study offers resolutions to the SDGs with relevant examples. We conclude with
offering our opinion on the current state of SysME and the direction it should
move forward in the generations to come, explicitly focusing on addressing the
SDGs.
PMID- 28696001
TI - An ArsR/SmtB family member regulates arsenic resistance genes unusually arranged
in Thermus thermophilus HB27.
AB - Arsenic resistance is commonly clustered in ars operons in bacteria; main ars
operon components encode an arsenate reductase, a membrane extrusion protein, and
an As-sensitive transcription factor. In the As-resistant thermophile Thermus
thermophilus HB27, genes encoding homologues of these proteins are interspersed
in the chromosome. In this article, we show that two adjacent genes, TtsmtB,
encoding an ArsR/SmtB transcriptional repressor and, TTC0354, encoding a Zn2+
/Cd2+ -dependent membrane ATPase are involved in As resistance; differently from
characterized ars operons, the two genes are transcribed from dedicated promoters
upstream of their respective genes, whose expression is differentially regulated
at transcriptional level. Mutants defective in TtsmtB or TTC0354 are more
sensitive to As than the wild type, proving their role in arsenic resistance.
Recombinant dimeric TtSmtB binds in vitro to both promoters, but its binding
capability decreases upon interaction with arsenate and, less efficiently, with
arsenite. In vivo and in vitro experiments also demonstrate that the arsenate
reductase (TtArsC) is subjected to regulation by TtSmtB. We propose a model for
the regulation of As resistance in T. thermophilus in which TtSmtB is the
arsenate sensor responsible for the induction of TtArsC which generates arsenite
exported by TTC0354 efflux protein to detoxify cells.
PMID- 28696002
TI - Mitochondrial dysfunction is an acute response of articular chondrocytes to
mechanical injury.
AB - : Mitochondrial (MT) dysfunction is known to occur in chondrocytes isolated from
end-stage osteoarthritis (OA) patients, but the role of MT dysfunction in the
initiation and early pathogenesis of post-traumatic OA (PTOA) remains unclear.
The objective of this study was to investigate chondrocyte MT function
immediately following mechanical injury in cartilage, and to determine if the
response to injury differed between a weight bearing region (medial femoral
condyle; MFC) and a non-weight bearing region (distal patellofemoral groove; PFG)
of the same joint. Cartilage was harvested from the MFC and PFG of 10 neonatal
bovids, and subjected to injurious compression at varying magnitudes (5-17 MPa, 5
34 GPa/s) using a rapid single-impact model. Chondrocyte MT respiratory function,
MT membrane polarity, chondrocyte viability, and cell membrane damage were
assessed in situ. Cartilage impact resulted in MT depolarization and impaired MT
respiratory function within 2 h of injury. Cartilage from a non-weight bearing
region of the joint (PFG) was more sensitive to impact-induced MT dysfunction and
chondrocyte death than cartilage from a weight-bearing surface (MFC). Our
findings suggest that MT dysfunction is an acute response of chondrocytes to
cartilage injury, and that MT may play a key mechanobiological role in the
initiation and early pathogenesis of PTOA. CLINICAL SIGNIFICANCE: Direct
therapeutic targeting of MT function in the early post-injury time frame may
provide a strategy to block perpetuation of tissue damage and prevent the
development of PTOA. (c) 2017 Orthopaedic Research Society. Published by Wiley
Periodicals, Inc. J Orthop Res 36:739-750, 2018.
PMID- 28696003
TI - Relative abundance of 'Candidatus Tenderia electrophaga' is linked to cathodic
current in an aerobic biocathode community.
AB - Biocathode microbial communities are proposed to catalyse a range of useful
reactions. Unlike bioanodes, model biocathode organisms have not yet been
successfully cultivated in isolation highlighting the need for culture
independent approaches to characterization. Biocathode MCL (Marinobacter,
Chromatiaceae, Labrenzia) is a microbial community proposed to couple CO2
fixation to extracellular electron transfer and O2 reduction. Previous
metagenomic analysis of a single MCL bioelectrochemical system (BES) resulted in
resolution of 16 bin genomes. To further resolve bin genomes and compare
community composition across replicate MCL BES, we performed shotgun metagenomic
and 16S rRNA gene (16S) sequencing at steady-state current. Clustering pooled
reads from replicate BES increased the number of resolved bin genomes to 20, over
half of which were > 90% complete. Direct comparison of unassembled metagenomic
reads and 16S operational taxonomic units (OTUs) predicted higher community
diversity than the assembled/clustered metagenome and the predicted relative
abundances did not match. However, when 16S OTUs were mapped to bin genomes and
genome abundance was scaled by 16S gene copy number, estimated relative abundance
was more similar to metagenomic analysis. The relative abundance of the bin
genome representing 'Ca. Tenderia electrophaga' was correlated with increasing
current, further supporting the hypothesis that this organism is the
electroautotroph.
PMID- 28696004
TI - Frequent loss of inositol polyphosphate-5-phosphatase in oropharyngeal squamous
cell carcinoma.
PMID- 28696005
TI - The Japanese Generally Accept Human-Animal Chimeric Embryo Research but Are
Concerned About Human Cells Contributing to Brain and Gametes.
PMID- 28696006
TI - Genetic variation in the DNA repair pathway as a potential determinant of
response to platinum-based chemotherapy in breast cancer.
AB - Platinum-based chemotherapy is often used as a first-line treatment for patient
with breast cancer. Platinum agents bind to DNA, forming adducts that contain
intra and inter-strand crosslinks. It is possible that genetic variations of the
DNA repair pathways may affect the activity, or efficacy of platinum, and hence
resistance to platinum chemotherapy may be related to these genetic variants. We
have summarized the known variants in the DNA repair pathway that have been
reported to predict the response to platinum-based therapy in breast cancer.
PMID- 28696007
TI - Comparison of conventional cytology and SurePath in split thyroid fine needle
aspiration materials.
AB - OBJECTIVE: The aim of the present study was to compare the cytomorphological
features and cytopathological diagnoses in thyroid aspiration materials prepared
by SurePath(r) (SP) and conventional cytology (CC). MATERIALS AND METHODS: Fine
needle aspiration (FNA) materials from 180 thyroid nodules were divided into two
groups to prepare three conventional smears and one SP slide. Twenty-nine
cytomorphological features of thyroid lesions were compared in the CC and SP
slides. The Kappa coefficiency was determined for each. The cytopathological
diagnosis of CC and SP were compared. RESULTS: The feature with the lowest Kappa
coefficient was the haemorrhagic background, whereas nuclear molding had the
highest Kappa coefficient. The rates of the atypical and suspicious
cytopathological diagnostic categories were decreased, whereas the rates of
benign and malignant categories were increased in SP. When the cytopathological
diagnoses of CC and SP were compared with the histopathological diagnoses of the
31 thyroidectomy materials, the results were similar. CONCLUSION: The common
problems seen in CC, such as an excessive number of slides, a haemorrhagic
background and air drying artefact in the SP method were not encountered. Through
these advantages, the rate of the indeterminate cytopathological diagnosis was
low in SP. In addition to those advantages, the increased rates of non-diagnostic
cases, the difficulty in evaluating the cytomorphologic features owing to
tridimensional structures and the smaller size of the cells and the presence of
tridimensional structures uninterpreted microscopically were the disadvantages of
SP. The present results showed that SP could be used instead of CC in thyroid
cytopathology.
PMID- 28696008
TI - Sustainable therapies by engineered bacteria.
AB - The controlled in situ delivery of biologics (e.g. enzymes, cytokines,
antibodies) by engineered bacteria of our microbiome will allow the sustainable
production of these complex and expensive drugs locally in the human body,
overcoming many of the technical and economical barriers currently associated
with the global use of these potent medicines. We provide examples showing how
engineered bacteria can be effective treatments against multiple pathologies,
including autoimmune and inflammatory diseases, metabolic disorders, diabetes,
obesity, infectious diseases and cancer, hence contributing to achieve the Global
Sustainable Goal 3: ensure healthy lives and promote well-being for all at all
ages.
PMID- 28696009
TI - Concise Review: The Deleterious Effects of Cigarette Smoking and Nicotine Usage
and Mesenchymal Stem Cell Function and Implications for Cell-Based Therapies.
AB - Stem cell sources for cell-based therapeutics are often screened for infectious
agents and genetic diseases prior to implantation; however, there are other risk
factors that are often overlooked, which may ultimately lead to less efficacious
clinical outcomes. One such risk factor is exposure of mesenchymal stem cells
(MSCs) to cigarette smoke or nicotine. Recent data have shown that exposure to
cigarette smoke or nicotine leads to decreased regenerative potential, namely
decreased proliferation, decreased migration, and decreased differentiation
potential of exposed MSCs. This review provides a brief introduction into MSCs
and their respective niches and a summary regarding the interactions of
cigarettes and nicotine with MSCs populations. Specifically, the effects of
cigarette smoke and nicotine on the regenerative potential of MSCs (i.e.,
proliferation, migration, and differentiation) will be covered with an emphasis
on considerations for the development of future cell-based clinical trials and
therapies. Stem Cells Translational Medicine 2017;6:1815-1821.
PMID- 28696010
TI - Myelin as an inflammatory mediator: Myelin interactions with complement,
macrophages, and microglia in spinal cord injury.
AB - Spinal cord injury (SCI) triggers chronic intraspinal inflammation consisting of
activated resident and infiltrating immune cells (especially
microglia/macrophages). The environmental factors contributing to this protracted
inflammation are not well understood; however, myelin lipid debris is a hallmark
of SCI. Myelin is also a potent macrophage stimulus and target of complement
mediated clearance and inflammation. The downstream effects of these neuroimmune
interactions have the potential to contribute to ongoing pathology or facilitate
repair. This depends in large part on whether myelin drives pathological or
reparative macrophage activation states, commonly referred to as M1
(proinflammatory) or M2 (alternatively) macrophages, respectively. Here we review
the processes by which myelin debris may be cleared through macrophage surface
receptors and the complement system, how this differentially influences
macrophage and microglial activation states, and how the cellular functions of
these myelin macrophages and complement proteins contribute to chronic
inflammation and secondary injury after SCI.
PMID- 28696012
TI - Inhibition of SNK-SPAR signaling pathway promotes the restoration of motor
function in a rat model of ischemic stroke.
AB - This study aimed to investigate the effects of SPAR signaling pathway on the
restoration of motor function in ischemic stroke (IS). Sprague-Dawley male rats
were separated into the control and sham groups, as well as the group for middle
cerebral artery occlusion (MCAO) model establishment. Successfully established
rat ischemic models were randomly divided into model, SNKMCAO-del and pcDNA3.1
SNK groups. The evaluation of motor function among the rats in each group was
assessed using a balance beam, a screen test and the Garcia scoring method.
CatWalk gait analysis was employed to evaluate the effect of the SNK signaling
pathway on rat motor function. Triphenyltetrazolium chloride (TTC) and TUNEL
staining were techniques were utilized for cerebral infarction (CI) area as well
for hippocampal neuron apoptosis. The quantitative real-time polymerase chain
reaction (qRT-PCR) and western blotting methods were performed to detect mRNA and
protein expressions of SNK and SPAR. When compared with the model group, the
SNKMCAO-del group displayed decreased motor function score and CI area, while
contrasting results were observed in the pcDNA3.1-SNK group. According to the
results obtained from the CatWalk gait analysis, the SNKMCAO-del group showed a
clear improvement compared to the model group whereas the pcDNA3.1-SNK group
exhibited poorer results than the model group in the objective parameters of the
study, such as movement, speed, running duration, print area, maximal contact
area, maximal, mean intensity, and stride length. These findings suggested that
SNK gene silencing promotes motor function by inhibiting the SNK-SPAR signaling
pathway in rats with ischemic stroke.
PMID- 28696013
TI - The role of diffusion MRI in neuroscience.
AB - Diffusion-weighted imaging has pushed the boundaries of neuroscience by allowing
us to examine the white matter microstructure of the living human brain. By doing
so, it has provided answers to fundamental neuroscientific questions, launching a
new field of research that had been largely inaccessible. We briefly summarize
key questions that have historically been raised in neuroscience concerning the
brain's white matter. We then expand on the benefits of diffusion-weighted
imaging and its contribution to the fields of brain anatomy, functional models
and plasticity. In doing so, this review highlights the invaluable contribution
of diffusion-weighted imaging in neuroscience, presents its limitations and
proposes new challenges for future generations who may wish to exploit this
powerful technology to gain novel insights.
PMID- 28696015
TI - Strength of commonly used spinal needles: the ability to deform and resist
deformation.
AB - We investigated the strength of commonly used spinal needles in relation to the
amount of deformation, and registered forces during standardised testing. We
investigated differences between manufacturers for the same length and gauge of
Luer and non-Luer needles, and examined the effect of the internal stylet in
terms of needle strength. A specialised rig was designed to perform the testing
in both the horizontal and axial plane, reflecting common industrial tests and
clinical use. Needles from four commonly used manufacturers were used (Vygon,
Becton Dickinson, B Braun, and Pajunk). Needles of 25 G and 27 G were tested in
90-mm and 120-mm lengths. We found significant differences in terms of the size
of final deformation and 'toughness'/resistance to deformation between needles of
different brands. There were also significant differences between horizontal
tests conducted as an industry standard and our own axial test. This may have
bearing on clinical use in terms of the incidence of bending and breakage. The
presence of the internal stylet resulted in significantly greater toughness in
many needles, but had little effect on the degree of deformation. Comparison of
Luer and non-Luer needles of the same brand and size showed few significant
differences in strength. This result is reassuring, given the imminent change
from Luer to non-Luer needles that is to occur in the UK.
PMID- 28696014
TI - Effect of metformin on ossification and inflammation of fibroblasts in ankylosing
spondylitis: An in vitro study.
AB - Ankylosing spondylitis (AS) is an autoimmune disease characterized by fibroblasts
ossification. However, effective drug therapy for AS is lacking. As an
antidiabetic drug, metformin has demonstrated an antiosteogenic effect on
osteoblasts in vitro. And it is also a kind of specific agonists for adenosine 5'
monophosphate activated protein kinase (AMPK), which is blocked in the process of
AS. Given the role in antiosteogenesis and AMPK activating, metformin was
investigated of its effect on fibroblasts harvested from capsular ligament of
patients with femoral neck fracture and AS. Osteogenic specific makers (Alp,
Bglap, Runx2, Bmp2, and Col1) in fibroblasts administered with metformin (20
MUg/mL) were detected by ALP staining, alizarin red staining, qPCR, and Western
blotting after 7 and 14 days of culture. Inflammation genes (il1-beta and il6)
and pathway (Pi3k, Akt, and Ampk) associated markers were also evaluated. Our
results showed that osteogenic specific markers were greatly downregulated and
ossification was effectively inhibited in AS fibroblasts after addition of
metformin. Levels of inflammation markers were also decreased by metformin. Thus,
metformin exerts potent effect on suppression of ossification and inflammation in
AS fibroblasts via the activation of Pi3k/Akt and AMPK pathways, which may be
developed as a potential agent for treatment of AS.
PMID- 28696016
TI - Central nervous system relapse of rhabdomyosarcoma.
AB - PURPOSE: The optimal management of central nervous system (CNS) relapse of
rhabdomyosarcoma (RMS) is unclear. We examined diagnosis, management, and
outcomes of patients with RMS developing CNS relapse. METHODS: Records of 23
patients diagnosed with CNS relapse between 1999 and 2016 were reviewed. Median
age at presentation of CNS relapse was 15 years (range, 1-34 years). High-risk
features at initial presentation were as follows: 16 alveolar patients, 13 Stage
IV, and 13 with primary tumor in parameningeal locations. RESULTS: CNS relapse
occurred at a median 12 months (range, 1-23 months) from diagnosis and most
common presenting symptoms were headache (n = 9), nausea/vomiting (n = 8), visual
difficulty (n = 5), and none (n = 5). Leptomeningeal metastases were detected in
21 patients while only 2 developed parenchymal metastases without leptomeningeal
involvement. Fifteen patients received CNS-directed radiation therapy (RT),
including craniospinal irradiation to a median 36 Gy (range, 18-36 Gy) and/or
whole brain radiotherapy to a median 30 Gy (range, 6-41.4 Gy). Three patients
received concurrent chemotherapy. Follow-up magnetic resonance imaging was
conducted in 13 patients after RT initiation with 8 demonstrating improvement, 2
with stable disease, and 3 with progression. Twelve patients were tested for
reactivity to I-131-labeled monoclonal antibody 8H9, and three tested positive
and received at least one intra-Ommaya dose; all three lived >12 months post-CNS
relapse. Twenty-one patients died of CNS disease and two of metastatic disease at
other sites. Median survival post-CNS relapse was 5 months (range, 0.1-49
months). CONCLUSIONS: The prognosis for patients with RMS developing CNS relapse
remains poor. Treatment including CNS-directed RT should be considered and
investigation into preventative therapies is warranted.
PMID- 28696017
TI - Reassortant DS-1-like G1P[4] Rotavirus A strains generated from co-circulating
strains in Vietnam, 2012/2013.
AB - One major mechanism by which Rotavirus A (RVA) evolves is genetic reassortment
between strains with different genotype constellations. However, the parental
strains of the reassortants generated have seldom been identified. Here, the
whole genome of two suspected reassortants, RVA/Human-wt/VNM/SP127/2013/G1P[4]
and RVA/Human-wt/VNM/SP193/2013/G1P[4], with short RNA electropherotypes were
examined by Illumina MiSeq sequencing and their ancestral phylogenies
reconstructed. Their genotype constellation, G1-P[4]-I2-R2-C2-M2-A2-N2-T2-E2-H2,
indicated that they were G1 VP7 mono-reassortants possessing DS-1-like genetic
backbones. The two strains were ?99.7% identical across the genome. While their
VP7 genes were ?99.7 identical to that of a Wa-like strain RVA/Human
wt/VNM/SP110/2012/G1P[8] which co-circulated during the 2012/2013 season, 10
genes were ?99.8% identical to that of the DS-1-like strains RVA/Human
wt/VNM/SP015/2012/G2P[4] (and SP108) that co-circulated during the season. The
identities were consistent with the phylogenetic relationships observed between
the genes of the reassortants and those of the afore-mentioned strains.
Consequently, the G1P[4] strains appear to have been generated by genetic
reassortment between SP110-like and SP015-like strains. In conclusion, this study
provides robust molecular evidence for the first time that G1P[4] strains
detected in Hanoi Vietnam were generated by inter-genogroup reassortment between
co-circulating G1P[8] and G2P[4] strains within the same place and season.
PMID- 28696018
TI - High-resolution mass spectrometric analysis of myo-inositol hexakisphosphate
using electrospray ionisation Orbitrap.
AB - RATIONALE: The phosphorus storage compound in grains, phytic acid, or myo
inositol hexakisphosphate (IP6), is important for nutrition and human health, and
is reportedly the most abundant organic phosphorus compound in soils. Methods for
its determination have traditionally relied on complexation with iron and
precipitation, acid digestion and measurement of phosphate concentration, or 31 P
NMR spectroscopy. Direct determination of phytic acid (and its homologues) using
mass spectrometry has, as yet, found limited application to environmental or
other complex matrices. The behaviour of phytic acid in electrospray ionisation
high-resolution mass spectrometry (ESI-HRMS) and its fragmentation, both in
source and via collision-induced dissociation, have not been studied so far.
METHODS: The negative ion mass spectrometry and tandem mass spectrometry (MS/MS)
of IP6, and the lower inositol pentakisphosphate (IP5), using an ESI-Orbitrap
mass spectrometer is described. The purity of the compounds was investigated
using anion-exchange chromatography. RESULTS: IP6 is highly anionic, forming
multiply charged ions and sodium adduct ions, which readily undergo dissociation
in the ESI source. MS/MS analysis of the phytic acid [M-2H]2- ion and fragment
ions and comparison with the full MS of the IP5 reference standard, and the MS/MS
spectrum of the pentakisphosphate [M-2H]2- ion, confirm the fragmentation pattern
of inositol phosphates in ESI. Further evidence for dissociation in the ion
source is shown by the effect of increasing the source voltage on the mass
spectrum of phytic acid. CONCLUSIONS: The ESI-HRMS of inositol phosphates is
unusual and highly characteristic. The study of the full mass spectrum of IP6 in
ESI-HRMS mode indicates the detection of the compound in environmental matrices
using this technique is preferable to the use of multiple reaction monitoring
(MRM).
PMID- 28696019
TI - Postoperative bleeding risk after gastric endoscopic submucosal dissection during
antithrombotic drug therapy.
AB - BACKGROUND AND AIM: The safety of gastric endoscopic submucosal dissection (ESD)
in the antithrombotic drug users remains controversial. METHODS: Patients who
underwent gastric ESD at Okayama University Hospital between March 2006 and
February 2016 were enrolled. This study investigated the risk of post-ESD
bleeding according to the management of the antithrombotic drugs. RESULTS: One
thousand twenty lesions (872 patients) were enrolled. In a multivariate analysis,
heparin replacement (odds ratio [OR] 5.0, 95% confidence interval [CI] 1.8-14),
multiple antithrombotic drug use (OR 2.9, 95% CI 1.1-6.9), a resected specimen of
>= 33 mm in diameter (OR 2.7, 95% CI 1.5-5.4), Helicobacter pylori negativity (OR
2.2, 95% CI 1.3-3.7), and tumors located in the lower third of the stomach (OR
1.7, 95% CI 1.0-2.9) were significant risk factors for post-ESD bleeding, while
the continuation of aspirin or cilostazol was not (OR 2.6, 95% CI 0.72-7.8). The
bleeding rate of the continuation group was comparable with that of the all
cessation group among single antithrombotic drug users (4.5% vs 4.4%, P = 1.0);
however, the rate of the continuation group was significantly higher than that of
the all cessation group among multiple antithrombotic drug users (67% vs 15%, P =
0.020). CONCLUSIONS: The risk of post-ESD bleeding differed according to the
management of the antithrombotic drugs. The gastric ESD under the cessation or
continuation of aspirin or cilostazol monotherapy was acceptable. However,
multiple antithrombotic drug use or heparin replacement was associated with a
higher risk of post-ESD bleeding.
PMID- 28696020
TI - Complete durable response of a pediatric anaplastic oligodendroglioma to
temozolomide alone: Case report and review of literature.
AB - Anaplastic oligodendroglioma (AO) is rare in children. Treatment typically
consists of varying combinations of surgery, chemotherapy, and radiotherapy. We
present a pediatric case of frontal lobe AO with periventricular subcallosal
extension and local leptomeningeal involvement. The isocitrate dehydrogenase
(IDH) wild-type tumor was MGMT methylated and contained an ATRX mutation, BRAF
alteration, and 1p/19q co-deletion; a combination of alterations mostly
encountered in pediatric oligodendrogliomas. The patient underwent a near total
resection and had a complete, durable response to temozolomide alone, suggesting
that conservative management without radiation may be appropriate in some cases.
We review the literature of this uncommon subtype of glioma in children.
PMID- 28696021
TI - Expanded Indacene-Tetrathiafulvalene Scaffolds: Structural Implications for Redox
Properties and Association Behavior.
AB - Redox-controlled dimerization of tetrathiafulvalene (TTF) derivatives is an
important tool for achieving reversible assemblies. Herein, the synthesis and
characterization of indacene-TTF hybrids, in which the central core is fused to
naphtho or benzothieno units, are reported. The orientation of these units has a
strong influence on the redox properties, with regard to the number of electrons
involved in the first oxidation event and the ability of the oxidized forms to
associate. The formation of mixed-valence and pi-dimer complexes is turned off
for those systems in which geometrical constraints provide nonplanar pi-systems.
Introduction of bulky substituents presents another way of preventing
association, as revealed by studies of indenofluorene and diindenoanthracene
scaffolds with (triisopropylsilyl)ethynyl groups. Horner-Wadsworth-Emmons
reactions present a general synthetic protocol to access superextended TTFs, by
using diones of polycyclic conjugated hydrocarbons as substrates.
PMID- 28696022
TI - Outcomes in Pancreas Transplantation With Exocrine Drainage Through a
Duodenoduodenostomy Versus Duodenojejunostomy.
AB - Until recently, pancreas transplantation has mostly been performed with exocrine
drainage via duodenojejunostomy (DJ). Since 2012, DJ was substituted with
duodenoduodenostomy (DD) in our hospital, allowing endoscopic access for
biopsies. This study assessed safety profiles with DD versus DJ procedures and
clinical outcomes with the DD technique in pancreas transplantation. DD patients
(n = 117; 62 simultaneous pancreas-kidney [SPKDD ] and 55 pancreas
transplantation alone [PTADD ] with median follow-up 2.2 years) were compared
with DJ patients (n = 179; 167 SPKDJ and 12 PTADJ ) transplanted in the period
1998-2012 (pre-DD era). Postoperative bleeding and pancreas graft vein thrombosis
requiring relaparotomy occurred in 17% and 9% of DD patients versus 10% (p =
0.077) and 6% (p = 0.21) in DJ patients, respectively. Pancreas graft rejection
rates were still higher in PTADD patients versus SPKDD patients (p = 0.003).
Hazard ratio (HR) for graft loss was 2.25 (95% CI 1.00, 5.05; p = 0.049) in PTADD
versus SPKDD recipients. In conclusion, compared with the DJ procedure, the DD
procedure did not reduce postoperative surgical complications requiring
relaparatomy or improve clinical outcomes after pancreas transplantation despite
serial pancreatic biopsies for rejection surveillance. It remains to be seen
whether better rejection monitoring in DD patients translates into improved long
term pancreas graft survival.
PMID- 28696023
TI - MCDA swing weighting and discrete choice experiments for elicitation of patient
benefit-risk preferences: a critical assessment.
AB - PURPOSE: Multiple criteria decision analysis swing weighting (SW) and discrete
choice experiments (DCE) are appropriate methods for capturing patient
preferences on treatment benefit-risk trade-offs. This paper presents a
qualitative comparison of the 2 methods. METHODS: We review and critically assess
similarities and differences of SW and DCE based on 6 aspects: comprehension by
study participants, cognitive biases, sample representativeness, ability to
capture heterogeneity in preferences, reliability and validity, and robustness of
the results. RESULTS: The SW choice task can be more difficult, but the workshop
context in which SW is conducted may provide more support to patients who are
unfamiliar with the end points being evaluated or who have cognitive impairments.
Both methods are similarly prone to a number of biases associated with preference
elicitation, and DCE is prone to simplifying heuristics, which limits its
application with large number of attributes. The low cost per patient of the DCE
means that it can be better at achieving a representative sample, though SW does
not require such large sample sizes due to exact nature of the collected
preference data. This also means that internal validity is automatically enforced
with SW, while the internal validity of DCE results needs to be assessed
manually. CONCLUSIONS: Choice between the 2 methods depends on characteristics of
the benefit-risk assessment, especially on how difficult the trade-offs are for
the patients to make and how many patients are available. Although there exist
some empirical studies on many of the evaluation aspects, critical evidence gaps
remain.
PMID- 28696024
TI - A genome-wide association analysis for carcass traits in a commercial Duroc pig
population.
AB - We performed a genome-wide association study to map the genetic determinants of
carcass traits in 350 Duroc pigs typed with the Porcine SNP60 BeadChip.
Association analyses were carried out using the gemma software. The proportion of
phenotypic variance explained by the SNPs ranged between negligible to moderate
(hSNP2= 0.01-0.30) depending on the trait under consideration. At the genome-wide
level, we detected one significant association between backfat thickness between
the 3rd and 4th ribs and six SNPs mapping to SSC12 (37-40 Mb). We also identified
several chromosome-wide significant associations for ham weight (SSC11: 51-53 Mb,
three SNPs; 67-68 Mb, two SNPs), carcass weight (SSC11: 66-68 Mb, two SNPs),
backfat thickness between the 3rd and 4th ribs (SSC12: 21 Mb, one SNP; 33-40 Mb,
17 SNPs; 51-58 Mb, two SNPs), backfat thickness in the last rib (SSC12: 37 Mb,
one SNP; 40-41 Mb, nine SNPs) and lean meat content (SSC13: 34 Mb, three SNPs and
SSC16: 45.1 Mb, one SNP; 62-63 Mb, 10 SNPs; 71-75 Mb, nine SNPs). The ham weight
trait-associated region on SSC11 contains two genes (UCHL3 and LMO7) related to
muscle development. In addition, the ACACA gene, which encodes an enzyme for the
catalysis of fatty acid synthesis, maps to the SSC12 (37-41 Mb) region harbouring
trait-associated regions for backfat thickness traits. Sequencing of these
candidate genes may help to uncover the causal mutations responsible for the
associations found in the present study.
PMID- 28696025
TI - A novel VWF variant associated with type 2 von Willebrand disease in German
Wirehaired Pointers and German Shorthaired Pointers.
AB - Von Willebrand disease (VWD), caused by deficiency of the von Willebrand factor
(VWF), is the most common bleeding disorder in humans and dogs. The complete cDNA
encoding VWF of a German Wirehaired Pointer with type 2 VWD was sequenced, and we
found four variants that alter the amino acid sequence. These variants were:
c.1657T>G corresponding to p.Trp553Gly; c.1777G>A (p.Glu593Lys); c.4937A>G
(p.Asn1646Ser) and c.5544G>A (p.Met1848Ile). A haplotype of the c.1657G, c.1777A
and c.4937G alleles co-segregated with the VWF antigen level in a four-generation
pedigree with the disease. Healthy dogs of the breed were found that were
homozygous for the c.1777A or the c.5544A allele, indicating that these variants
do not cause VWD. Dogs that were homozygous for the c.4937G allele and had no
signs of a bleeding disorder were observed in the Chinese Crested dog breed.
Thus, only the c.1657G variant was found in the homozygous state exclusively in
VWD affecteds, and this variant is the strongest candidate to be the cause of VWD
type 2 in the German Wirehaired Pointer breed. A screen of German Shorthaired
Pointers indicated that the variant also segregates with VWD in this breed.
PMID- 28696026
TI - A genome-wide association study for a proxy of intermuscular fat level in the
Italian Large White breed identifies genomic regions affecting an important
quality parameter for dry-cured hams.
AB - Intermuscular fat content in protected designations of origin dry-cured hams is a
very important meat quality trait that affects the acceptability of the product
by the consumers. An excess in intermuscular fat (defined as the level of fat
deposition between leg muscles) is a defect that depreciates the final product.
In this study we carried out a genome-wide association study for visible
intermuscular fat (VIF) of hams in the Italian Large White pig breed. This trait
was evaluated on the exposed muscles of green legs in 1122 performance-tested
gilts by trained personnel, according to a classification scale useful for
routine and cheap evaluation. All animals were genotyped with the Illumina
PorcineSNP60 BeadChip. The genome-wide association study identified three QTL
regions on porcine chromosome 1 (SSC1; accounting for ~79% of the SNPs below the
5.0E-04 threshold) and SSC2, two on SSC7 and one each on SSC3, SSC6, SSC9, SSC11,
SSC13, SSC15, SSC16 and SSC17. The most significant SNP (ALGA0004143 on SSC1 at
77.3 Mb; PFDR < 0.05), included in the largest QTL region which spanned about
6.8 Mb on SSC1, is located within the glutamate ionotropic receptor kainate type
subunit 2 (GRIK2) gene. Functional annotation of all genes included in QTL
regions for VIF suggested that intermuscular fat in the Italian Large White breed
is a complex trait apparently influenced by complex biological mechanisms also
involving obesity-related processes. These QTL target mainly chromosome regions
different from those affecting subcutaneous and intramuscular fat deposition.
PMID- 28696027
TI - atz-1 Influences meiosis to maintain germline chromosomal stability in
Caenorhabditis elegans.
AB - Exchange of genetic information during meiosis occurs in all sexually reproducing
species to produce haploid gametes from diploid cells. This process involves
tight coordination of a meiotic specific cohesin complex, the synaptonemal
complex, and DNA damage repair mechanisms. In this study, we describe a putative
myosin heavy chain protein orthologous to human myosin 1, F28D1.2, which we named
Abnormal Transition Zone (atz-1). Deletion of atz-1 results in embryonic
lethality and a depleted transition zone, accompanied by reduced expression of
the meiotic cohesin protein, REC-8. atz-1 mutants display disorganized and
aggregated chromosomal bodies in diakinetic oocytes. In addition to this, atz-1
mutants are hypersensitive to mild inhibition of DNA damage repair, suggesting
that DNA replication in atz-1 mutants is impaired. Moreover, the atz-1 mutant
phenotype is germline specific and resupplying somatically expressed atz-1 does
not rescue the reproductive defects associated with atz-1 mutants. Overall, our
data suggest that atz-1 contributes to meiosis and maintains germline chromosomal
stability.
PMID- 28696028
TI - Pretransplant functional imaging and outcome in pediatric patients with
relapsed/refractory Hodgkin lymphoma undergoing autologous transplantation.
AB - BACKGROUND: Pretransplant functional imaging (FI), particularly a negative
positron emission tomography (PET), is a strong predictor of outcome in adults
with relapsed or refractory Hodgkin lymphoma (HL), but data in pediatrics are
limited. METHODS: The medical records of 49 consecutive pediatric patients, who
received autologous transplant at a single institution, were retrospectively
analyzed. All patients had either gallium or PET scan before transplant and were
conditioned with carmustine, etoposide, cytarabine, and melphalan (BEAM).
Deauville scores were retrospectively assigned for patients with PET (score >= 4
positive). RESULTS: Of the 49 patients (median age, 16.2 years), 41 (84%) were
pretransplant FI negative and eight (16%) were pretransplant FI positive, after
first- to fourth-line salvage therapy, and a median of two salvage cycles.
Eighteen patients (37%) received posttransplant radiation. At a median follow up
of 46 months, 45 patients (92%) were alive and disease free, and there were three
nonrelapse deaths and only one relapse death (Deauville score of 5). The 4-year
progression-free survival (PFS) for the entire cohort was 92% (95% confidence
interval [CI]: 78-97), and PFS based on pretransplant disease status was 95% (95%
CI: 82-99%) in the negative FI group versus 75% (95% CI: 31-93) if positive FI (P
= 0.057). CONCLUSION: Our analysis revealed outstanding outcomes for children and
adolescents with relapsed/refractory HL. There were too few relapses to identify
the predictive value of pretransplant metabolic status, but pediatric patients
with relapsed/refractory HL and a negative pretransplant FI had excellent
survival.
PMID- 28696029
TI - Insurance status and mortality among patients with AIDS.
AB - OBJECTIVES: The aim of the study was to evaluate risk factors for mortality,
including health care insurance status, among patients with AIDS in the era of
modern combination antiretroviral therapy (cART). METHODS: This study was part of
the prospective, multicentre, observational Longitudinal Study of the Ocular
Complications of AIDS (LSOCA). Patients were classified as having private health
care insurance, Medicare, Medicaid, or no insurance. Hazard ratios (HRs) for
death were calculated using proportional hazards regression models and staggered
entries, anchored to the AIDS diagnosis date. RESULTS: Among 2363 participants
with AIDS, 97% were treated with cART. At enrolment, 31% of participants had
private insurance, 29% had Medicare, 24% had Medicaid, and 16% were uninsured.
Noninfectious, age-related diseases, such as hypertension, diabetes, and renal
disease, were more frequent among persons with Medicare than among those with
private insurance. Compared with those who were privately insured, mortality was
greater among participants with Medicare [adjusted HR (HRadj ) 1.35; 95%
confidence interval (CI) 1.08-1.67; P = 0.008]. Among participants with a
suppressed HIV viral load, compared with those who were privately insured, HRadj
values for mortality were 1.93 (95% CI 1.08-3.44; P = 0.02) for those with
Medicare and 2.09 (95% CI 1.02-4.27; P = 0.04) for those with Medicaid. Mortality
among initially uninsured participants was not significantly different from that
for privately insured participants, but these participants typically obtained ART
and insurance during follow-up. Compared with privately insured participants,
time-updated HRadj values for mortality were 1.34 (95% CI 1.05-1.70; P = 0.02)
for those with Medicare, 1.34 (95% CI 1.01-1.80; P = 0.05) for those with
Medicaid, and 1.35 (95% CI 0.97-1.88; P = 0.05) for those who were uninsured.
CONCLUSIONS: In persons with AIDS, compared with those with private insurance,
those with public insurance had increased mortality, possibly as a result of a
greater burden of noninfectious, age-related diseases.
PMID- 28696030
TI - Evaluation of BAG3 levels in healthy subjects, hypertensive patients, and
hypertensive diabetic patients.
AB - BAG3 is a member of human BAG (Bcl-2-associated athanogene) proteins and plays a
role in apoptosis, cell adhesion, cytoskeleton remodeling, and autophagy. The aim
of this study was to evaluate BAG3 levels in healthy subjects, hypertensive
patients, and hypertensive diabetic patients. We enrolled 209 Caucasian adults,
of both sex, 18-75 years of age, 77 were healthy controls, 62 were affected by
hypertension, and 70 were affected by hypertension and type 2 diabetes. All
patients underwent an assessment that included medical history, physical
examination, vital signs, a 12-lead electrocardiogram, measurements of systolic
(SBP), and diastolic blood pressure (DBP), heart rate (HR), fasting plasma
glucose (FPG), glycated hemoglobin (HbA1c ), triglycerides (TG), transaminases,
high sensitivity C-reactive protein (Hs-CRP), and BAG3. We observed higher blood
pressure values in hypertensive, and hypertensive diabetic patients compared to
controls. As expected, FPG and HbA1c were higher in diabetic hypertensive
patients, compared to the other two groups. No Tg levels differences were
recorded among the three groups. Hs-CRP was higher in diabetic hypertensive
patients compared to healthy subjects. Finally, BAG3 levels were higher in
hypertensives, and hypertensive diabetic patients compared to controls. We
observed higher levels of BAG3 in hypertensive patients compared to healthy
controls, and even higher levels in hypertensive diabetic patients compared to
healthy subjects. This paper could be the first of a long way to identify
potential involvement of deregulated BAG3 levels in cardiometabolic diseases.
PMID- 28696031
TI - A biotechnologist's dream: 'doubly green' processes.
PMID- 28696032
TI - Research Review: Harnessing the power of individual participant data in a meta
analysis of the benefits and harms of the Incredible Years parenting program.
AB - BACKGROUND: Parenting programs aim to reduce children's conduct problems through
improvement of family dynamics. To date, research on the precise benefits and
possible harms of parenting programs on family well-being has been unsystematic
and likely to be subject to selective outcome reporting and publication bias.
Better understanding of program benefits and harms requires full disclosure by
researchers of all included measures, and large enough numbers of participants to
be able to detect small effects and estimate them precisely. METHODS: We obtained
individual participant data for 14 of 15 randomized controlled trials on the
Incredible Years parenting program in Europe (total N = 1,799). We used
multilevel modeling to estimate program effects on 13 parent-reported outcomes,
including parenting practices, children's mental health, and parental mental
health. RESULTS: Parental use of praise, corporal punishment, threats, and
shouting improved, while parental use of tangible rewards, monitoring, or laxness
did not. Children's conduct problems and attention deficit hyperactivity disorder
(ADHD) symptoms improved, while emotional problems did not. Parental mental
health (depressive symptoms, self-efficacy, and stress) did not improve. There
was no evidence of harmful effects. CONCLUSIONS: The Incredible Years parenting
program improves the aspects of family well-being that it is primarily designed
to improve: parenting and children's conduct problems. It also improves parent
reported ADHD symptoms in children. Wider benefits are limited: the program does
not improve children's emotional problems or parental mental health. There are no
signs of harm on any of the target outcomes.
PMID- 28696033
TI - Response to: Mesenchymal Stem Cells: Time to Change the Name!
PMID- 28696034
TI - Fast noninvasive functional diffuse optical tomography for brain imaging.
AB - Advances in epilepsy studies have shown that specific changes in hemodynamics
precede and accompany seizure onset and propagation. However, it has been
challenging to noninvasively detect these changes in real time and in humans, due
to the lack of fast functional neuroimaging tools. In this study, we present a
functional diffuse optical tomography (DOT) method with the guidance of an
anatomical human head atlas for 3-dimensionally mapping the brain in real time.
Central to our DOT system is a human head interface coupled with a technique that
can incorporate topological information of the brain surface into the DOT image
reconstruction. The performance of the DOT system was tested by imaging motor
tasks-involved brain activities on N = 6 subjects (3 epilepsy patients and 3
healthy controls). We observed diffuse areas of activations from the
reconstructed [HbT] images of patients, relative to more focal activations for
healthy subjects. Moreover, significant pretask hemodynamic activations were also
seen in the motor cortex of patients, which indicated abnormal activities
persistent in the brain of an epilepsy patient. This work demonstrates that fast
functional DOT is a valuable tool for noninvasive 3-dimensional mapping of brain
hemodynamics.
PMID- 28696035
TI - Lin-Gettig syndrome: Craniosynostosis expands the spectrum of the KAT6B related
disorders.
AB - We report two patients with sagittal craniosynostosis, hypoplastic male
genitalia, agenesis of the corpus callosum, thyroid abnormalities, and dysmorphic
features which include short palpebral fissures and retrognathia. The clinical
presentation of both patients was initially thought to be suggestive of Lin
Gettig syndrome (LGS), a multiple malformation syndrome associated with
craniosynostosis that was initially reported in two brothers in 1990, with a
third patient reported in 2003. Our first patient was subsequently found through
exome sequencing to have a de novo mutation in KAT6B, c.4572dupT,
p.(Thr1525Tyrfs*16). The second patient was ascertained as possible LGS, but
KAT6B mutation testing was pursued clinically after the identification of the
KAT6B mutation in Patient 1, and identified a de novo mutation, c.4205_4206delCT,
p.(Ser1402Cysfs*5). The phenotypic spectrum of KAT6B mutations has been expanding
since identification of KAT6B mutations in genitopatellar syndrome (GPS) and Say
Barber Biesecker Young Simpson (SBBYS) syndrome patients. We show that
craniosynostosis, which has not been previously reported in association with
KAT6B mutations, may be part of the genitopatellar/Say Barber Biesecker Young
Simpson spectrum. These two patients also further demonstrate the overlapping
phenotypes of genitopatellar and SBBYS syndromes recently observed by others.
Furthermore, we propose that it is possible that one or more of the previous
cases of LGS may have also been due to mutation in KAT6B, and that LGS may
actually be a variant within the KAT6B spectrum and not a distinct clinical
entity.
PMID- 28696036
TI - Cervical artery dissection expands the cardiovascular phenotype in FBN1-related
Weill-Marchesani syndrome.
AB - Weill-Marchesani syndrome (WMS) is a rare form of acromelic dysplasia that is
characterized by distinctive skeletal, ocular, and cardiovascular abnormalities.
Previously described cardiac manifestations of WMS include aortic and pulmonary
valve stenosis, mitral valve prolapse, mitral stenosis, and QTc prolongation.
Autosomal dominant forms of WMS result from heterozygous pathogenic variants in
FBN1, a gene with a well characterized role in the pathogenesis of thoracic
aortic aneurysm (TAA) in the context of Marfan syndrome. In contrast, only one
patient has been reported with aortic disease in WMS. Although the risk of aortic
dissection from preceding TAA remains the leading cause of morbidity for
individuals with Marfan syndrome, rare reports of arterial dissection in the
peripheral vasculature have been described. Peripheral artery dissection has not
been previously reported in other FBN1-related diseases. We describe a three
generation family with FBN1-related WMS whose cardiovascular manifestations
include TAA and cervical artery dissection, thus expanding the cardiovascular
phenotype of WMS. Further research is required to quantify these risks and
establish appropriate recommendations for cardiovascular imaging, medical
management, and prophylactic surgical intervention in individuals with FBN1-
related acromelic dysplasia.
PMID- 28696037
TI - Unravelling biocomplexity of electroactive biofilms for producing hydrogen from
biomass.
AB - Leveraging nature's biocomplexity for solving human problems requires better
understanding of the syntrophic relationships in engineered microbiomes developed
in bioreactor systems. Understanding the interactions between microbial players
within the community will be key to enhancing conversion and production rates
from biomass streams. Here we investigate a bioelectrochemical system employing
an enriched microbial consortium for conversion of a switchgrass-derived bio-oil
aqueous phase (BOAP) into hydrogen via microbial electrolysis (MEC). MECs offer
the potential to produce hydrogen in an integrated fashion in biorefinery
platforms and as a means of energy storage through decentralized production to
supply hydrogen to fuelling stations, as the world strives to move towards
cleaner fuels and electricity-mediated transportation. A unique approach
combining differential substrate and redox conditions revealed efficient but rate
limiting fermentation of the compounds within BOAP by the anode microbial
community through a division of labour strategy combined with multiple levels of
syntrophy. Despite the fermentation limitation, the adapted abilities of the
microbial community resulted in a high hydrogen productivity of 9.35 L per L-day.
Using pure acetic acid as the substrate instead of the biomass-derived stream
resulted in a three-fold improvement in productivity. This high rate of
exoelectrogenesis signifies the potential commercial feasibility of MEC
technology for integration in biorefineries.
PMID- 28696038
TI - Recognizing syndromic hidradenitis suppurativa: a review of the literature.
AB - Hidradenitis suppurativa (HS) is an inflammatory skin disease causing painful
inflammation and suppuration. It may occur in rare syndromes: follicular
occlusion, Bazex-Dupre-Christol, Down's, KID, PAPASH, PASS, PASH, and SAPHO
syndromes, as well as Dowling-Degos disease. An overview of syndromic HS may
inform the search for aetiological factors in HS. PubMed, Ovid and Web of Science
were systematically searched using '(hidradenitis OR acne invers*) AND (syndrome
OR KID OR PASS OR PAPA OR PASH OR SAPHO OR bazex-dupre OR 'dowling degos' OR
triad OR tetrad)' and Cochrane Library using 'hidradenitis OR acne invers*'. A
total of 82 articles were included in the final review. We summarize 134 cases
collected from the 82 included articles. The syndromes are discussed, focusing on
etiopathogenesis, clinical presentation and treatment. This study is based on
case reports; therefore, conclusions may be subject to the selection bias. These
syndromes are rare; however, it is important to recognize them, as treating them
may require a different approach. Three subtypes of syndromic hidradenitis are
suggested: syndromes with known genetic abnormalities, syndromes characterized by
follicular plugging or structural defects, and syndromes with possible
autoinflammatory pathogenesis. There was no universally effective treatment for
syndromic HS, and treatment was individualized.
PMID- 28696039
TI - Systemic contact dermatitis induced by roots of Hosta plantaginea.
PMID- 28696040
TI - Fundus autofluorescence: the key in the diagnosis of maternally inherited
diabetes and deafness.
PMID- 28696041
TI - The contribution of microbial biotechnology to sustainable development goals:
microbiome therapies.
AB - Complex communities of microbes live on and in plants, humans and other animals.
These communities are collectively referred to as the microbiota or microbiome.
Plants and animals evolved to co-exist with these microbes. In mammals,
particular kinds of alteration of the microbiome (dysbiosis) are associated with
loss of health, most likely due to loss of microbial metabolites, signalling
molecules, or regulators of host pathways. Modern life-style diseases such as
Inflammatory Bowel Disease (IBD), Irritable Bowel Syndrome (IBS), type 2
diabetes, obesity and metabolic syndrome have been linked to dysbiosis. These
multifactorial diseases involve multiple risk factors and triggers, depletion of
certain gut microbiota species being one of them. Live Biotherapeutics operate by
restoring microbial products or activities in affected subjects. They are being
developed as adjuncts, alternatives or new treatment options for diseases that
affect a growing proportion of global citizens.
PMID- 28696042
TI - Reduced vision in highly myopic eyes without ocular pathology: the ZOC-BHVI high
myopia study.
AB - BACKGROUND: The aim was to investigate the relationship of the magnitude of
myopia with visual acuity in highly myopic eyes without ocular pathology.
METHODS: Twelve hundred and ninety-two highly myopic eyes (up to -6.00 DS both
eyes, no astigmatic cut-off) with no ocular pathology from the ZOC-BHVI high
myopia study in China, had cycloplegic refraction, followed by subjective
refraction and visual acuities and axial length measurement. Two logistic
regression models were undertaken to test the association of age, gender,
refractive error, axial length and parental myopia with reduced vision. RESULTS:
Mean group age was 19.0 +/- 8.6 years; subjective spherical equivalent refractive
error was -9.03 +/- 2.73 D; objective spherical equivalent refractive error was
8.90 +/- 2.60 D and axial length was 27.0 +/- 1.3 mm. Using visual acuity, 82.4
per cent had normal vision, 16.0 per cent had mildly reduced vision, 1.2 per cent
had moderately reduced vision, 0.3 per cent had severely reduced vision and no
subjects were blind. The percentage with reduced vision increased with spherical
equivalent to 74.5 per cent from -15.00 to -39.99 D, axial length to 67.7 per
cent of eyes from 30.01 to 32.00 mm and age to 22.9 per cent of those 41 years
and over. Spherical equivalent and axial length were significantly associated
with reduced vision (p < 0.0001). Age and parental myopia were not significantly
associated with reduced vision. Gender was significant for one model (p = 0.04).
CONCLUSION: Mildly reduced vision is common in high myopia without ocular
pathology and is strongly correlated with greater magnitudes of refractive error
and axial length. Better understanding is required to minimise reduced vision in
high myopes.
PMID- 28696043
TI - The bioelectric well: a novel approach for in situ treatment of hydrocarbon
contaminated groundwater.
AB - Groundwater contamination by petroleum hydrocarbons (PHs) is a widespread problem
which poses serious environmental and health concerns. Recently, microbial
electrochemical technologies (MET) have attracted considerable attention for
remediation applications, having the potential to overcome some of the limiting
factors of conventional in situ bioremediation systems. So far, field-scale
application of MET has been largely hindered by the limited availability of
scalable system configurations. Here, we describe the 'bioelectric well' a
bioelectrochemical reactor configuration, which can be installed directly within
groundwater wells and can be applied for in situ treatment of organic
contaminants, such as PHs. A laboratory-scale prototype of the bioelectric well
has been set up and operated in continuous-flow regime with phenol as the model
contaminant. The best performance was obtained when the system was inoculated
with refinery sludge and the anode potentiostatically controlled at +0.2 V versus
SHE. Under this condition, the influent phenol (25 mg l-1 ) was nearly completely
(99.5 +/- 0.4%) removed, with an average degradation rate of 59 +/- 3 mg l-1 d
and a coulombic efficiency of 104 +/- 4%. Microbial community analysis revealed a
remarkable enrichment of Geobacter species on the surface of the graphite anode,
clearly pointing to a direct involvement of this electro-active bacterium in the
current-generating and phenol-oxidizing process.
PMID- 28696045
TI - Efficient and Mild Ullmann-Type N-Arylation of Amides, Carbamates, and Azoles in
Water.
AB - A simple, sustainable, efficient, mild, and low-cost protocol was developed for d
glucose-assisted Cu-catalyzed Ullmann reactions in water for amides, carbamates,
and nitrogen-containing heterocycles. The reaction was compatible with diverse
aryl/heteroaryl iodides, giving highly substituted pyridine, indole, or indazole
rings. This method offers an attractive alternative to existing protocols,
because the reaction proceeds in aqueous media, occurs at or near ambient
temperature, and provides the N-arylated products in good to high yields.
PMID- 28696044
TI - Practice patterns of palliative radiation therapy in pediatric oncology patients
in an international pediatric research consortium.
AB - BACKGROUND/OBJECTIVES: The practice of palliative radiation therapy (RT) is based
on extrapolation from adult literature. We evaluated patterns of pediatric
palliative RT to describe regimens used to identify opportunity for future
pediatric-specific clinical trials. DESIGN/METHODS: Six international
institutions with pediatric expertise completed a 122-item survey evaluating
patterns of palliative RT for patients <=21 years old from 2010 to 2015. Two
institutions use proton RT. Palliative RT was defined as treatment with the goal
of symptom control or prevention of immediate life-threatening progression.
RESULTS: Of 3,225 pediatric patients, 365 (11%) were treated with palliative
intent to a total of 427 disease sites. Anesthesia was required in 10% of
patients. Treatment was delivered to metastatic disease in 54% of patients.
Histologies included neuroblastoma (30%), osteosarcoma (18%), leukemia/lymphoma
(12%), rhabdomyosarcoma (12%), medulloblastoma/ependymoma (12%), Ewing sarcoma
(8%), and other (8%). Indications included pain (43%), intracranial symptoms
(23%), respiratory compromise (14%), cord compression (8%), and abdominal
distention (6%). Sites included nonspine bone (35%), brain (16% primary tumors,
6% metastases), abdomen/pelvis (15%), spine (12%), head/neck (9%), and
lung/mediastinum (5%). Re-irradiation comprised 16% of cases. Techniques employed
three-dimensional conformal RT (41%), intensity-modulated RT (23%), conventional
RT (26%), stereotactic body RT (6%), protons (1%), electrons (1%), and other
(2%). The most common physician-reported barrier to consideration of palliative
RT was the concern about treatment toxicity (83%). CONCLUSION: There is
significant diversity of practice in pediatric palliative RT. Combined with
ongoing research characterizing treatment response and toxicity, these data will
inform the design of forthcoming clinical trials to establish effective regimens
and minimize treatment toxicity for this patient population.
PMID- 28696046
TI - Survival impact of lymphocyte infiltration into the tumor of hepatocellular
carcinoma in hepatitis B virus-positive or non-B non-C patients who underwent
curative resection.
AB - AIM: The prognostic value of lymphocyte infiltration into hepatocellular
carcinoma (HCC) is still controversial, and it has not been reported in hepatitis
B virus (HBV)-positive or non-B non-C (NBNC) HCC. The aim of this study is to
assess the prognostic significance of lymphocyte infiltrate in tumor for HBV
positive and NBNC HCC patients. METHODS: This study investigated 145 HBV-positive
or NBNC patients who underwent hepatectomy for HCC between January 2001 and May
2009. Cumulative recurrence rate, overall survival (OS), and clinicopathological
parameters were analyzed according to lymphocyte infiltration in tumor. RESULTS:
In patients with low lymphocyte infiltration, the 5-year recurrence rate was
higher and OS was poor (86.4 and 44.1%, respectively) than that of the patients
with high lymphocyte infiltration (55.3 and 83.7%, respectively). Multivariate
analyses revealed that independent risk factors for recurrence were low albumin
value (hazard ratio [HR] 2.33, P = 0.009), high American Joint Committee on
Cancer (AJCC) T stage (HR 2.31, P < 0.0001), high alpha-fetoprotein (AFP) value
(HR 2.06, P = 0.005), and low lymphocyte infiltration (HR 2.50, P = 0.0001). The
independent risk factors for OS were low albumin value (HR 3.69, P = 0.003), high
AJCC T stage (HR 2.10, P = 0.049), high AFP value (HR 3.98, P < 0.001), and low
lymphocyte infiltration (HR 3.47, P = 0.001). CONCLUSIONS: Lymphocyte infiltrate
in tumor is significantly associated high recurrence rate and poor overall
survival. Evaluation of the infiltrating lymphocyte could improve the prediction
of prognosis in HCC patients after curative resection.
PMID- 28696047
TI - A randomized trial of the effectiveness of the neutropenic diet versus food
safety guidelines on infection rate in pediatric oncology patients.
AB - BACKGROUND: The neutropenic diet (ND) is prescribed to avoid introduction of
bacteria into a host's gastrointestinal tract and reduce infection. Due to a lack
of evidence to support the ND, there continues to be debate among pediatric
oncologists regarding its usefulness. This prospective randomized controlled
trial evaluated the difference in neutropenic infection rates in pediatric
oncology patients randomized to Food and Drug Administration approved food safety
guidelines (FSGs) versus the ND plus FSGs during one cycle of chemotherapy.
PROCEDURE: Pediatric patients receiving cancer treatment with myelosuppressive
chemotherapy were eligible. Neutropenic infection was the primary outcome and
defined as (i) fever with neutropenia or (ii) hospital admission and treatment
for clinical infection and neutropenia. The rate of neutropenic infection was
compared with Student's t-test for independent samples. Documented infections
were identified by comprehensive chart review and compared between groups using a
chi2 test. RESULTS: One hundred fifty patients were randomly assigned to FSGs (n
= 73) or ND + FSGs (n = 77). The most common diagnoses were acute lymphoblastic
leukemia (32%) and sarcoma (32%). There was no significant difference between the
groups in the percentage of patients who developed neutropenic infection: FSGs
33% versus ND + FSGs 35% (P = 0.78). Patients randomized to ND + FSGs reported
that following the diet required more effort than those on FSGs alone.
CONCLUSION: The ND offers no benefit over FSGs in the prevention of infection in
pediatric oncology patients undergoing myelosuppressive chemotherapy and
adherence requires more effort for patients and families. Institutions caring for
children with cancer should consider replacing ND guidelines with FSGs.
PMID- 28696048
TI - Comparative selective retention of particle size classes in the gastrointestinal
tract of ponies and goats.
AB - There is a discrepancy in the literature on potential digesta separation
mechanisms in horses, with both a selective retention of fine and of large
particles postulated in different publications. To assess the net effect of such
mechanisms, we fed ponies on a hay-only diet a pulse dose of whole (unchopped)
marked hay together with a solute marker, collected faeces on a regular basis,
measured marker concentrations in whole faeces and in their large (2.0-16 mm),
medium (0.5-1.0 mm) and small (0.063-0.25 mm) particle fraction, and calculated
the corresponding mean retention times (MRTs). For comparison, the same
experiment was performed in goats. In goats, as expected, MRTsolute (35 hr) was
significantly shorter than MRTparticle (51 hr); only a very small fraction of
particle marker was excreted as large particles (2%); and the MRT of these large
particles was significantly shorter than that of small particles (with a relevant
difference of 8.6 hr), indicating that those few large particles that escape the
rumen do so mostly soon after ingestion. In ponies, MRTsolute (24 hr) did not
differ from MRTparticle (24 hr); a higher fraction of particle marker was
excreted as large particles (5%); and the MRT of these large particles was longer
than that of small particles (but with a non-relevant difference of less than 1
hr). These results indicate that no relevant net separation of digesta phases
occurs in horses and that selective particle retention mechanisms in the large
intestine are unlikely to represent important characteristics of the horse's
digestive physiology.
PMID- 28696049
TI - Increased nutritional value in food crops.
AB - Modern agriculture and horticulture must combine two objectives that seem to be
almost mutually exclusive: to satisfy the nutritional needs of an increasing
human population and to minimize the negative impact on the environment. These
two objectives are included in the Goal 2 of the 2030 Agenda for Sustainable
Development of the United Nations: 'End hunger, achieve food security and
improved nutrition and promote sustainable agriculture'. Enhancing the
nutritional levels of vegetables would improve nutrient intake without requiring
an increase in consumption. In this context, the use of beneficial rhizospheric
microorganisms for improving, not only growth and yield, but also the nutrient
quality of crops represents a promising tool that may respond to the challenges
for modern agriculture and horticulture and represents an alternative to the
genetic engineering of crops. This paper summarizes the state of the art, the
current difficulties associated to the use of rhizospheric microorganisms as
enhancers of the nutritional quality of food crops as well as the future
prospects.
PMID- 28696050
TI - The complexity of growth failure in children receiving tyrosine kinase inhibitor
therapy for chronic myelogenous leukemia.
PMID- 28696051
TI - Unexpected acute renal injury after high-dose etoposide phosphate and total body
irradiation in children undergoing hematopoietic stem cell transplantation.
AB - High-dose etoposide phosphate, a water-soluble prodrug of etoposide, may be used
after total body irradiation (TBI) in pediatric allogeneic bone marrow
transplantation for lymphoblastic leukemia. In a retrospective study of 21
children treated at the Nancy University Hospital (2000-2014), we identified
unprecedentedly an unexpectedly high incidence (57%) of acute renal injury
following etoposide phosphate infusion. Patients who developed renal function
impairment experienced more severe mucositis but had outcomes similar to those
who did not. No risk factors were identified. We speculate that the etoposide
phosphate diluent, dextran 40, may have been the causative agent in these post
TBI renal toxicity cases.
PMID- 28696052
TI - Dermoscopic and reflectance confocal microscopy features of cutaneous squamous
cell carcinoma.
AB - BACKGROUND: Squamous cell carcinoma (SCC) of the skin is a highly prevalent
neoplasm. The management and the prognosis of this tumour are dependent on its
invasiveness and its grade of differentiation. OBJECTIVES: To evaluate whether
specific dermoscopic and reflectance confocal microscopy (RCM) criteria can
predict the diagnosis of invasive SCC vs. in situ SCC and poorly differentiated
compared with well- and moderately differentiated SCC. METHODS: Dermoscopic and
RCM images of SCC were retrospectively evaluated for the presence of predefined
criteria. RESULTS: Among 143 SCCs, 121 cases had a complete set of images and
thus were included in the study set. The head and neck area was the most
frequently involved body site (74/121; 61.1%) followed by extremities (36/121,
29.7%) and trunk (11/121, 9.1%). Seventy tumours were in situ (57.8%), while 51
were invasive (42.1%), of these 11 were poorly differentiated (21.5%), 16 were
moderately differentiated (31.3%), and 24 were well differentiated (47.0%). Chi
squared analysis demonstrated that invasive SCCs were characterized by
polymorphic vessels, erosion/ulceration, architectural disarrangement, speckled
nucleated cells in the dermis, irregularly dilated vessels and absence of
hyperkeratosis. Buttonhole vessels, white structureless areas and dotted or
glomerular vessels were significantly associated with in situ lesions. Poorly
differentiated SCCs were typified by red areas, erosion/ulceration and
architectural disarrangement. Well- or moderately differentiated SCCs were
associated with white areas and speckled nucleated cells in the epidermis.
CONCLUSION: Clinical, dermoscopic and RCM images provide useful information that
should be integrated in order to achieve the optimal therapeutic management for
the patient.
PMID- 28696053
TI - Learning effectiveness and satisfaction of international medical students:
Introducing a Hybrid-PBL curriculum in biochemistry.
AB - A biochemistry course is a fundamental but important subject in medical education
in China. In recent years, the number of international medical students has
increased. Curriculum reform in biochemistry teaching is needed because of the
knowledge limitations of students, a close linkage of biochemical content with
clinics, the shortcomings of lecture-centered teaching, and the requirements for
early clinical practice training and competence. In this study, we analyzed a
novel curriculum reform, "Hybrid-PBL," which combined problem-based learning
(PBL) with biochemistry lectures and was implemented for biochemical teaching at
Dalian Medical University (DMU) in China. The change in curriculum affected 189
international medical students. This study selected two PBL cases concerning the
basic biochemical issues of carbohydrate metabolism and liver biochemistry for
the analysis, and ten examples of learning issues for each case were reported by
the international students. A questionnaire was utilized to evaluate students'
perceptions of the Hybrid-PBL, and examination scores were analyzed to assess the
curriculum reform in biochemistry teaching. A statistical analysis revealed that
the Hybrid-PBL curriculum was well accepted by the international students as an
effective supplement to lecture-centered teaching programs. The students obtained
more abilities, higher examination scores, and an improved understanding of
biomedical information from the Hybrid-PBL program than from conventional
teaching methods. Our study was an innovative trial that applied a PBL curriculum
to the specific discipline of biochemistry and may provide a potential and
promising new teaching method that can be widely utilized. (c) 2017 by The
International Union of Biochemistry and Molecular Biology, 45(4):336-342, 2017.
PMID- 28696054
TI - Undergraduate research as curriculum.
AB - To date, national interests, policies, and calls for transformation of
undergraduate education have been the main drivers of research integration into
the undergraduate curriculum, briefly described here. The New Horizons in
Biochemistry and Molecular Biology Education conference at the Weizmann Institute
of Science (Israel) this fall presents an exciting opportunity to discuss
integration of undergraduate research into the curriculum and other cutting-edge
topics in biochemistry and molecular biology education from a cross-national
perspective. I look forward to exploring prospects for international
collaboration on research and development of course-based undergraduate research
experiences and on STEM education in general. (c) 2017 by The International Union
of Biochemistry and Molecular Biology, 45(4):293-298, 2017.
PMID- 28696055
TI - Practices and exploration on competition of molecular biological detection
technology among students in food quality and safety major.
AB - With the increasing importance in the application of the molecular biological
detection technology in the field of food safety, strengthening education in
molecular biology experimental techniques is more necessary for the culture of
the students in food quality and safety major. However, molecular biology
experiments are not always in curricula of Food quality and safety Majors. This
paper introduced a project "competition of molecular biological detection
technology for food safety among undergraduate sophomore students in food quality
and safety major", students participating in this project needed to learn the
fundamental molecular biology experimental techniques such as the principles of
molecular biology experiments and genome extraction, PCR and agarose gel
electrophoresis analysis, and then design the experiments in groups to identify
the meat species in pork and beef products using molecular biological methods.
The students should complete the experimental report after basic experiments,
write essays and make a presentation after the end of the designed experiments.
This project aims to provide another way for food quality and safety majors to
improve their knowledge of molecular biology, especially experimental technology,
and enhances them to understand the scientific research activities as well as
give them a chance to learn how to write a professional thesis. In addition, in
line with the principle of an open laboratory, the project is also open to
students in other majors in East China University of Science and Technology, in
order to enhance students in other majors to understand the fields of molecular
biology and food safety. (c) 2017 by The International Union of Biochemistry and
Molecular Biology, 45(4):343-350, 2017.
PMID- 28696057
TI - Optimizing the chances of success in the search for epigenetic biomarkers:
Embracing genetic variation.
AB - The emphasis on clinical translation in biomedical research continues to grow.
This focus has been particularly notable in those investigators using epigenetic
approaches to decipher the biology of complex behavioral disorders. As a result
of these efforts, reproducible findings for several disorders, such as smoking,
have been generated, giving rise to hopes that biomarkers for other behavioral
illnesses would be forthcoming. Unfortunately, that biomedical cornucopia has not
yet materialized. In this editorial, we review progress to date and discuss
barriers to generating epigenetic biomarkers for complex behavioral disorders. We
highlight the need to incorporate information on genetic variation and develop
more powerful bioinformatics tools in order to optimize the likelihood of
success. We emphasize that searches should focus on clearly defined, readily
distinguishable behavioral constructs and suggest that some well-intentioned
methods, such as correction for cellular heterogeneity, may actually impede the
identification of clinically relevant biomarkers in peripheral blood. Finally, we
describe how the understanding created by the development of these biomarkers may
lead to more valid animal models of neuropsychiatric illness. We conclude that
the prospects for epigenetic biomarkers for complex disorders are bright, but
emphasize that the journey to the clinical implementation of these findings will
be a slow, iterative process.
PMID- 28696058
TI - Early postnatal gentamicin and ceftazidime treatment in normal and food
restricted neonatal wistar rats: Implications for kidney development.
AB - BACKGROUND: Up to two-thirds of premature born neonates are treated for
infections with aminoglycosides such as gentamicin. Although acute toxicities are
well described, there is uncertainty on developmental changes after treatment of
premature born neonates. We studied the effect of gentamicin and ceftazidime on
kidney development in the rat. Additionally, we evaluated the modulating effect
of extrauterine growth restriction. METHODS: On postnatal day (PND) 2, Wistar
rats were cross-fostered into normal sized litters (12 pups) or large litters (20
pups) to create normal food (NF) or food restricted (FR) litters to simulate
growth restriction and dosed daily intraperitoneally with placebo, 4 mg/kg of
gentamicin or 50 mg/kg ceftazidime until PND 8. Gentamicin pharmacokinetics were
studied in a separate group of animals. Kidneys were weighed. Renal expression of
18 developmental genes was evaluated by quantitative PCR on PND 8. On PND 35,
glomerular number was assessed by stereology and glomerular generations were
counted. RESULTS: Food restricted litters showed 22% less body weight compared
with controls by day 35 (p < 0.001), 1.4- to 1.5-fold down regulation of Renin,
Oat1, and Agtr1a (p < 0.05) expression and a 12% reduction in glomerular numbers
(mean 30841 vs. 35187, p < 0.001), whereas glomerular generation count was
unaffected. Gentamicin pharmacokinetic parameters were found to be in a human
clinical range (mean maximum concentration in plasma of 4.88 mg/L and mean area
under the plasma-concentration time curve up to the last measured concentration
after 4 hr of 10.71 mg.h/L for sexes combined) and all endpoints were unaffected.
Ceftazidime reduced Renin expression by 1.7-fold (p < 0.01). CONCLUSION: Our
experiments showed that gentamicin at clinical levels did not disturb kidney
development, ceftazidime can affect Renin expression, and extrauterine growth
restriction impairs kidney development, but did not modulate potential drug
toxicity. Birth Defects Research 109:1228-1235, 2017. (c) 2017 Wiley Periodicals,
Inc.
PMID- 28696059
TI - Metal and metalloid biorecovery using fungi.
AB - Bioleaching is a proven bioprocess for metal recovery by solution from solid
matrices, while a bioprecipitation or biomineralization approach is of potential
for biorecovery from solution. Fungi can directly and indirectly mediate the
formation of many kinds of minerals, including oxides, phosphates, carbonates and
oxalates, as well as elemental forms of metals and metalloids such as Ag, Se and
Te. Fungal capabilities may offer a potentially useful contribution to
biotechnological and physico-chemical methods for metal recovery.
PMID- 28696060
TI - Wine secondary aroma: understanding yeast production of higher alcohols.
PMID- 28696061
TI - Outcomes and healthcare utilization in children and young adults with aplastic
anemia: A multiinstitutional analysis.
AB - BACKGROUND: Aplastic anemia is a bone marrow failure syndrome with high mortality
affecting children and young adults. Although current treatment guidelines
recommend hematopoietic stem cell transplant (HCT) for patients with matched
sibling donors, outcomes with alternate donor options have been improving.
PROCEDURE: We analyzed a validated multiinstitutional pediatric cohort using one
of the largest pediatric and young adult database, the Pediatric Health
Information System, for patients diagnosed with aplastic anemia (AA) from 2006 to
2015. Outcomes with upfront and salvage transplants were analyzed along with
healthcare utilization. RESULTS: Among 2,169 patients in the study period, almost
20% underwent HCT, while others received immunosuppressive therapy. In a
multivariate model, there was no significant difference in mortality with upfront
or salvage transplants (odds ratio [OR] 1.24, 95% confidence interval [CI] 0.6
2.58, P = 0.567), while every platelet transfusion was associated with higher
mortality (OR 1.37, 95% CI 1.12-1.67, P = 0.002). Healthcare utilization was
significantly higher in salvage transplants requiring frequent hospitalization
and transfusion requirements. Treatment mortality and graft failure rates were
significantly reduced in the salvage transplant group in recent years (2011-2015
as compared to 2006-2010). CONCLUSION: As outcomes with HCT continue to improve
in severe AA, transplant with good alternate donors should be considered upfront
in children and young adults.
PMID- 28696062
TI - Advancing nursing science with meta-analyses.
PMID- 28696063
TI - Complete remission of refractory hepatoblastoma after liver transplantation in a
child with sorafenib monotherapy: A new hope?
PMID- 28696064
TI - Harnessing microbiome-based biotechnologies for sustainable mitigation of nitrous
oxide emissions.
AB - Achieving the Sustainable Development Goal of climate change mitigation within
this century will require adoption of new innovative technologies to control
emissions of nitrous oxide (N2 O), an important greenhouse gas leading to global
warming. This is particularly important in the face of growing fertilizer
consumption and continuous land degradation. Currently used tools to mitigate N2
O emissions are based on agrochemical inputs and agronomic practices. Emerging
technologies include plant breeding approaches to manipulate microbiome
activities in agro-ecosystems, and microbial biotechnology approaches for in situ
microbiome manipulation and engineering via use of biochemical, cellular and
genome-editing methods. This article assessed the likely contribution of
microbial biotechnology to the mitigation of N2 O emissions and discussed how to
facilitate the development of environmental-friendly microbiome-based
biotechnology for sustainable climate change mitigation.
PMID- 28696065
TI - The dynamics of the bacterial communities developed in maize silage.
AB - Ensilage provides an effective means of conserving summer-grown green forage to
supply as winter feed to ruminants. The fermentation process involved in the
ensilage process relies on lactic acid bacteria (LAB). Here, 16S ribosomal DNA
amplicon pyrosequencing was used to follow the dynamic behaviour of the LAB
community during the ensilage of maize biomass, with a view to identify the key
species involved in the process. The biomass used for ensilage was a single-cross
maize hybrid, harvested at the milk-line stage. The crop was grown at three
contrasting locations. Aspects of the physico-chemical composition of the
material and the LAB species present were sampled at 0, 3, 6, 14, 21 and 32 days
after ensilage was initiated. In all three cases, members of the Leuconostocaceae
family dominated the epiphytic bacterial community, notably Leuconostoc and
Weissella, but some variation was noted in the abundance of certain
Leuconostocaceae and Lactobacillaceae species, as well as that of some
Acetobacteraceae, Enterobacteriaceae and Moraxellaceae species. The constellation
of the microbiome which developed during the ensilage process differed markedly
from that of the epiphytic one, with Lactobacillaceae, particularly Lactobacillus
and Pediococcus spp. dominating. The abundance of heterofermentative
Leuconostocaceae spp. in the epiphytic community and the extent of the transition
from hetero- to homo-fermentation during the initial ensilage period are
important factors in determining silage quality.
PMID- 28696066
TI - Strategies for combating persister cell and biofilm infections.
AB - Bacterial cells are constantly exposed to environmental stress; for example,
almost all cells must endure starvation, and antimicrobials, of course, are
administered to kill bacteria. These stressed cells enter a resting state known
as persistence in which they become tolerant to nearly all antibiotics without
undergoing genetic change. These dormant cells survive courses of antibiotics, as
antibiotics are most effective against actively metabolizing cells, and
reconstitute infections. In humans, most of these bacterial infections occur in
biofilms in which bacteria attach to one another via secreted proteins,
polysaccharides and even DNA. Herein, biotechnological methods are described to
combat persister cells and to eradicate biofilms by understanding the genetic
basis of both phenomena.
PMID- 28696068
TI - Gas fermentation for commodity chemicals and fuels.
AB - Gas fermentation is a microbial process that contributes to at least four of the
sustainable development goals (SDGs) of the United Nations. The process converts
waste and greenhouse gases into commodity chemicals and fuels. Thus, world's
climate is positively affected. Briefly, we describe the background of the
process, some biocatalytic strains, and legal implications.
PMID- 28696067
TI - The contribution of microbial biotechnology to mitigating coral reef degradation.
AB - The decline of coral reefs due to anthropogenic disturbances is having
devastating impacts on biodiversity and ecosystem services. Here we highlight the
potential and challenges of microbial manipulation strategies to enhance coral
tolerance to stress and contribute to coral reef restoration and protection.
PMID- 28696069
TI - Hepatocellular carcinoma-associated single-nucleotide variants and deletions
identified by the use of genome-wide high-throughput analysis of hepatitis B
virus.
AB - This study investigated hepatitis B virus (HBV) single-nucleotide variants (SNVs)
and deletion mutations linked with hepatocellular carcinoma (HCC). Ninety-three
HCC patients and 108 non-HCC patients were enrolled for HBV genome-wide next
generation sequencing (NGS) analysis. A systematic literature review and a meta
analysis were performed to validate NGS-defined HCC-associated SNVs and
deletions. The experimental results identified 60 NGS-defined HCC-associated
SNVs, including 41 novel SNVs, and their pathogenic frequencies. Each SNV was
specific for either genotype B (n = 24) or genotype C (n = 34), except for nt53C,
which was present in both genotypes. The pathogenic frequencies of these HCC
associated SNVs showed a distinct U-shaped distribution pattern. According to the
meta-analysis and literature review, 167 HBV variants from 109 publications were
categorized into four levels (A-D) of supporting evidence that they are
associated with HCC. The proportion of NGS-defined HCC-associated SNVs among
these HBV variants declined significantly from 75% of 12 HCC-associated variants
by meta-analysis (Level A) to 0% of 10 HCC-unassociated variants by meta-analysis
(Level D) (P < 0.0001). PreS deletions were significantly associated with HCC, in
terms of deletion index, for both genotypes B (P = 0.030) and C (P = 0.049). For
genotype C, preS deletions involving a specific fragment (nt2977-3013) were
significantly associated with HCC (HCC versus non-HCC, 6/34 versus 0/32, P =
0.025). Meta-analysis of preS deletions showed significant association with HCC
(summary odds ratio 3.0; 95% confidence interval 2.3-3.9). Transfection of Huh7
cells showed that all of the five novel NGS-defined HCC-associated SNVs in the
small surface region influenced hepatocarcinogenesis pathways, including
endoplasmic reticulum-stress and DNA repair systems, as shown by microarray, real
time polymerase chain reaction and western blot analysis. Their carcinogenic
mechanisms are worthy of further research. Copyright (c) 2017 Pathological
Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
PMID- 28696070
TI - The association between three attitude-related indexes of oral hygiene and
secondary implant failures: A retrospective longitudinal study.
AB - OBJECTIVE: This study evaluated the strength of the association between three
widely used clinical indexes considered as distal behavioural indicators of
attitude-related oral status (an index of oral hygiene, the plaque index [PI] and
two periodontal indexes, that is the presence of bleeding on probing [BOP] and of
pockets probing depth [PPD]) and secondary implant failure due to peri
implantitis in patients rehabilitated with cemented prosthesis. MATERIALS AND
METHODS: The study included patients who underwent implant-prosthetic
rehabilitation and had joined the programme of maintenance of the same hospital.
Implant failures, number of months between implant insertion and implant loading,
and patients' surgical protocol were monitored and recorded. Further, PI, BOP and
PPD-all attitude-related indicators of oral hygiene and periodontal inflammation
were recorded and related, in terms of odds ratios (ORs ) and corresponding risk
factors, to secondary implant failures. RESULTS: A total of 1427 patients (2673
implants) were enrolled. The follow-up ranged from 1.5 to 9 years (mean 5.3
years+/-1.3). The cumulative survival rate was 98.01%. Thirty-two patients (36
implants, 1.36% of all implants) had implant failure. A statistically significant
association between PI, BOP, PPD and secondary failures due to peri-implantitis
was observed. CONCLUSION: Within the limitations of this study, all three
attitude-related behavioural indicators-the plaque index (PI), bleeding on
probing (BOP) and abnormal probing pocket depth (PPD)-proved to be significant
risk indicators for secondary implant failure due to peri-implantitis, both from
a clinical and from a socio-psychological attitude-related perspective.
PMID- 28696071
TI - Conversion of Cellulose into Amphiphilic Alkyl Glycosides Catalyzed by Aquivion,
a Perfluorosulfonic Acid Polymer.
AB - The perfluorosulfonic acid (PFSA) Aquivion PW98 is an amphiphilic solid superacid
which is shown to catalyze the conversion of cellulose into amphiphilic alkyl
glycosides (AAGs) in 85 % yield (with 97 % selectivity). The process involves a
mechanocatalytic depolymerization of cellulose followed by a direct glycosylation
with n-dodecanol. In comparison to H2 SO4 and solid acid catalysts commonly
employed in cellulose processing, Aquivion PFSA PW98 is not only recyclable but
also exhibits superior catalytic performances in terms of yield, selectivity, and
reactor productivity.
PMID- 28696072
TI - Comparison of three S-beta-CDs with different degrees of substitution for the
chiral separation of 12 drugs in capillary electrophoresis.
AB - Three kinds of sulfated beta-cyclodextrin (S-beta-CD), including a single isomer,
heptakis-6-sulfato-beta-cyclodextrin (HS-beta-CD), degree of substitution (DS) of
7, which was synthesized in our laboratory and another two commercialized
randomly substituted mixtures, a sulfated beta-cyclodextrin with DS of 7 to 11,
as well as a highly sulfated-beta-cyclodextrin with DS of 12 to 15, were used for
the enantioresolution of 12 drugs (the beta-blockers, phenethylamines, and
anticholinergic agents) in capillary electrophoresis. The enantioseparation under
varying concentrations of S-beta-CD and background electrolyte pH were
systematically investigated and compared. Based on the experimental results, the
effect of the nature of S-beta-CD and analyte structure on the enantioseparation
is discussed.
PMID- 28696073
TI - The top five challenges in wound care.
PMID- 28696077
TI - Legionnaires' disease in transplant recipients: A 15-year retrospective study in
a tertiary referral center.
AB - Legionnaires' disease (LD) can be fatal among high-risk transplant recipients. To
understand the epidemiology of LD, we reviewed 15-year longitudinal data from a
center in Seattle, Washington that cares for both solid organ transplant (SOT)
and hematopoietic cell transplant (HCT) recipients. We identified all laboratory
confirmed LD and extracted data on species, diagnostic modalities, clinical
presentation, management, and outcomes from medical records. Among 32 patients
with LD, transplant recipients made up the majority of diagnoses (22, 69%; SOT
10, HCT 12). Approximately 0.8% of transplant recipients who underwent Legionella
specific testing were positive. Non-pneumophila Legionella species (LNLP), which
are not detected by urinary antigen test, accounted for half the cases, led by
Legionella micdadei (32%). The severity and outcome between Legionella
pneumophila and LNLP infections were similar (attributed mortality, 36% vs 27%);
all LNLP deaths occurred in transplant recipients with L. micdadei. The clinical
and radiological features mimicked other opportunistic pathogens; 32% (n=7) were
not on empiric treatment at the time of diagnosis. These data add to the emerging
literature describing the importance of LD and highlight the need for both
routine Legionella testing on transplant recipients with pulmonary findings and
empiric Legionella-active antibiotic therapy.
PMID- 28696078
TI - The phenotype of EZH2 haploinsufficiency-1.2-Mb deletion at 7q36.1 in a child
with tall stature and intellectual disability.
AB - Weaver syndrome is a rare overgrowth syndrome with distinct facial features in
young children and variable learning disability. Heterozygous missense mutations
in EZH2 are present in over 90% of patients with Weaver syndrome but the exact
mechanism by which EZH2 mutations cause Weaver syndrome is unknown. We report an
11-year-old boy with a de novo 1.2-Mb deletion at 7q36.1 including EZH2 who has
tall stature, significant intellectual disability, and some physical features of
Weaver syndrome. Emerging evidence in the literature indicates that Weaver
syndrome EZH2 mutations may result in loss of function of the gene and our report
suggests that haploinsufficiency of EZH2 may replicate the clinical phenotype of
Weaver syndrome.
PMID- 28696079
TI - Impact of Protease Inhibitor-Based Anti-Retroviral Therapy on Outcomes for HIV+
Kidney Transplant Recipients.
AB - Excellent outcomes have been demonstrated among select HIV-positive kidney
transplant (KT) recipients with well-controlled infection, but to date, no
national study has explored outcomes among HIV+ KT recipients by antiretroviral
therapy (ART) regimen. Intercontinental Marketing Services (IMS) pharmacy fills
(1/1/01-10/1/12) were linked with Scientific Registry of Transplant Recipients
(SRTR) data. A total of 332 recipients with pre- and posttransplantation fills
were characterized by ART at the time of transplantation as protease inhibitor
(PI) or non-PI-based ART (88 PI vs. 244 non-PI). Cox proportional hazards models
were adjusted for recipient and donor characteristics. Comparing recipients by
ART regimen, there were no significant differences in age, race, or HCV status.
Recipients on PI-based regimens were significantly more likely to have an
Estimated Post Transplant Survival (EPTS) score of >20% (70.9% vs. 56.3%, p =
0.02) than those on non-PI regimens. On adjusted analyses, PI-based regimens were
associated with a 1.8-fold increased risk of allograft loss (adjusted hazard
ratio [aHR] 1.84, 95% confidence interval [CI] 1.22-2.77, p = 0.003), with the
greatest risk observed in the first posttransplantation year (aHR 4.48, 95% CI
1.75-11.48, p = 0.002), and a 1.9-fold increased risk of death as compared to non
PI regimens (aHR 1.91, 95% CI 1.02-3.59, p = 0.05). These results suggest that
whenever possible, recipients should be converted to a non-PI regimen prior to
kidney transplantation.
PMID- 28696080
TI - Aggregation-Induced Emission Characteristics of o-Carborane-Functionalized
Tetraphenylethylene Luminogens: The Influence of Carborane Cages on
Photoluminescence.
AB - Tetraphenylethylene (TPE)-carborane hybrids are constructed, and the impact of
carborane substituents on the aggregation-induced emission (AIE) characteristics
of TPE-cores has been investigated. When altering the 2-R-group on the carborane
unit with -H, -CH3 or phenyl group, the luminescent quantum yield of the
corresponding TPE derivatives can be manipulated from 0.18 to 0.63 in the solid
state. The emission color exhibits an obvious 100 nm shift (from blue to yellow).
PMID- 28696082
TI - A tribute to Edward B. Diethrich, MD, 1935-2017.
PMID- 28696081
TI - Peripheral artery disease: breakthroughs in techniques and treatments.
PMID- 28696083
TI - Artificial neural network for prediction of in-hospital mortality after open
repair of ruptured abdominal aortic aneurysm.
PMID- 28696084
TI - Can vitamin D deficiency influence muscle performance in postmenopausal women? A
multicenter retrospective study.
AB - BACKGROUND: The presence of the vitamin D receptor (VDR) has been recently
demonstrated in human muscle supporting the theory of a role of vitamin D in the
proliferation and differentiation of muscle cells. So far only few studies
investigated the association between vitamin D and muscle performance in
postmenopausal women. AIM: To define the functional impact of vitamin D
deficiency. DESIGN: Multicenter retrospective study. SETTING: Five Italian
outpatient services of Physical and Rehabilitation Medicine (PRM). POPULATION:
Postmenopausal women. METHODS: We divided the population in two groups based on
the threshold of 30 ng/mL as cut-off to define sufficient and insufficient serum
levels of 25-hydroxyvitamin D3 [25(OH)D3]. Outcome measures were: appendicular
lean mass (ALM); ALM-to-BMI ratio (ALMBMI); total fat mass (FM); visceral adipose
tissue (VAT); Hand Grip Strength (HGS); Knee Isometric Extension Strength (KES);
Short Physical Performance Battery (SPPB); 4-meter gait speed (4MGS). RESULTS: We
analyzed the data records of 401 postmenopausal women (mean age 66.93+/-8.47
years): 203 with hypovitaminosis D (mean age 66.81+/-8.11 years) and 198 with
normal levels of 25(OH)D3 (mean age 67.04+/-8.84 years). The analysis showed a
significant difference between the two groups in terms of: ALMBMI (0.002), FM
(P<0.001), VAT mass (0.010), VAT volume (P=0.006), HGS (P<0.001), KES (P<0.001),
SPPB score (P<0.001), percentage of people with a 4MGS<=0.8 m/s (P<0.001).
Furthermore, there were significant correlations (P<0.001) between serum levels
of 25(OH)D3 and HGS (r=0.323), KES (r=0.510), and SPPB sit to stand (r=-0.362)
and walking sub-scores (r=-0.312). CONCLUSIONS: This multicenter study
demonstrated that postmenopausal women with vitamin D deficiency had a
significant reduction of appendicular muscle strength and physical performance.
CLINICAL REHABILITATION IMPACT: This study reported the frequency of
hypovitaminosis D in postmenopausal women and its influence on the reduction of
muscle mass, strength, and physical performance in a typical population referring
to the physiatrist for musculoskeletal disorders.
PMID- 28696085
TI - Does fibroids surgery by endoscopy or laparotomy represent a malignancy threat?
AB - BACKGROUND: The aim of this study was to 1) estimate the incidence of unsuspected
uterine sarcoma in patients after myomectomies and hysterectomies for benign
uterine fibroids; 2) to assess the incidence of uterine sarcomas among patient
who had uterine fibroids or a suspicion of uterine sarcoma before undergoing the
surgical procedures. METHODS: Retrospective study in single center university
hospital. Patient's records with uterine fibroids and uterine sarcoma from 2003
to 2015 collected. Data presented as mean and standard deviation for continuous
variable and percentage for categorical variables. The exact Clopper-Pearson
interval was used to calculate 95% confidence interval. RESULTS: The total number
of women with uterine fibroids was 2269 and uterine sarcomas 7. Of these seven,
four were uterine leiomyosarcomas (ULMS), one endometrial sarcoma (ESS), one high
grade undifferentiated uterine sarcoma (HGUS) and one embryonal rhabdomyosarcoma
(ERMS). Six of these patients underwent direct open conventional cancer
treatment. The mean age of the patients with ULMS was 73.7+/-3.9 years.
Immunohistochemistry results indicated SMA(+), CD 10(+), desmin(+) and h
caldesmon(+). The two patients with HGUS and ERMS were also preoperatively
diagnosed with suspected malignancy and operated upon according. However, only
one woman 48 years old primarily diagnosed with benign uterine fibroids underwent
a laparoscopic subtotal hysterectomy (LSH) procedure; however, the histological
results detected an ESS. Immunohistochemistry showed CD10(+), desmin(+), smooth
muscle actin (SMA)(-), Aktin(-) and 5% Ki67(+).Two weeks after the initial
surgery, an open cervical stump resection with bilateral sapping-oophorectomy and
an omentectomy was performed. CONCLUSIONS: The frequency of unsuspected ESS was
1/2269 among the women who underwent myomectomies and hysterectomies for the
treatment of benign uterine fibroids. The total incidence of uterine sarcoma was
7/2275 among the patients who had presumed uterine fibroids or a suspicion of
uterine sarcoma prior to undergoing the surgical procedures.
PMID- 28696086
TI - Pregnancy after breast cancer: hope after the storm.
AB - Over the last few decades, long-term outcomes of young women with breast cancer
have greatly improved, raising several new survivorship needs which include
fertility preservation and pregnancy. The prejudice against pregnancy after
breast cancer is still alive among different healthcare providers (e.g.
gynecologists, oncologists, general practitioners) and women are often confused
and left alone in their family decision planning. All the available retrospective
data confirm pregnancy after breast cancer is safe both for the mother and the
offspring, also in women with hormone receptor positive disease. Timing of
conception after the disease is still a matter of debate, especially in women
receiving adjuvant endocrine therapy. A worldwide prospective trial is currently
assessing safety of interrupting endocrine treatment to allow conception.
Breastfeeding after breast cancer local therapy (surgery and radiation therapy)
can be challenging but should not be discouraged. Patients harboring pathogenic
mutations in breast cancer predisposing genes represent a small but growing
population facing specific problems, such as, among others, prophylactic breast
and ovarian surgery, and preimplantation genetic assessment, which all deserve a
dedicated and sensitive approach. This review will highlight and summarize the
current evidence and the research perspectives of pregnancy after breast cancer,
to provide healthcare professionals the information they need to properly counsel
young women with breast cancer who desire to conceive.
PMID- 28696087
TI - Leadless technology: a new paradigm for cardiac pacing?
AB - Leadless pacemaker (LP) technology was recently developed and introduced for
clinical purpose as an alternative to traditional systems in order to reduce
leads and pocket-related complications. Currently, two self-contained right
ventricular pacemakers implanted by using a femoral percutaneous approach have
been developed and initial results seem promising. Although the clinical use is
still limited to the right ventricular pacing, the LP currently represents a
valid and alternative solution in several settings, when the standard pacemaker
cannot be used or its use is associated with higher risk of complications.
Implementation of particular pacing algorithms in the near future will allow for
a VDD pacing mode with only a single ventricular component, whereas the next
evolution of technology will lead to develop multicomponent, communicating
leadless systems capable to perform a dual-chamber pacing or even a cardiac
resynchronization. The management after battery depletion is still controversial
and experience on retrievability is anecdotic. Long term data from registry are
necessary to reinforce the reliability of these systems in the real life and
randomized trials comparing LPs with traditional pacemaker will be essential to
better understand if the LP can become a new paradigm in cardiac pacing.
PMID- 28696088
TI - Cardiac lead management: the future of transvenous lead extraction approaches and
technologies.
AB - The implantation rate of cardiac implantable electronical devices (CIED) has
consistently increased in the last 20 years, so as related complication rates.
According, devices infections and malfunctions required the development of
appropriate strategies, including lead removal. Transvenous lead extraction (TLE)
is the gold standard for lead removal. The increasing rate of CIED implantations
and of CIED related complications highlight the importance of TLE. TLE scenario
is constantly evolving. TLE is a key procedure in lead management strategies.
Optimizing lead related technology and improving TLE practice across the world is
the cornerstone to improve safety and efficacy. We review the status of the art
of TLE, focusing on potential future implications and improvements in terms of
skillness and technologies. The increased number of extractions will increase the
necessity of safe and effective TLE. The use of adequate tools, techniques and
approaches, and an appropriate training are the cornerstone for safer procedures
achievement. New technologies, techniques and an appropriate training is
warranted across the world.
PMID- 28696089
TI - Prevention of sudden cardiac death: from wearable to subcutaneous cardioverter
defibrillator.
AB - The implantable cardioverter defibrillator (ICD) is today an indisputable
evidence-based treatment for cardiac sudden death both in primary and secondary
prevention. However many clinical conditions that would represent an indication
to ICD implantation, according to guidelines, may be potentially reversible or
may be accompanied by temporary contraindications to the implant. Moreover
transvenous cardioverter defibrillator implantation still carries a not
negligible risk of complications both acutely and at follow-up. The Wearable
Cardioverter Defibrillator and the Subcutaneous Defibrillator are two recently
developed technologies that can potentially overcome the aforementioned
limitations of traditional transvenous ICDs. This review will discuss the main
aspects of these 2 technologies, the data coming from clinical experiences and
future perspectives.
PMID- 28696090
TI - Wearable and Washable Conductors for Active Textiles.
AB - The emergence of stretchable electronics and its potential integration with
textiles have highlighted a challenge: Textiles are wearable and washable, but
electronic devices are not. Many stretchable conductors have been developed to
enable wearable active textiles, but little has been done to make them washable.
Here we demonstrate a new class of stretchable conductors that can endure wearing
and washing conditions commonly associated with textiles. Such a conductor
consists of a hydrogel, a dissolved hygroscopic salt, and a butyl rubber coating.
The hygroscopic salt enables ionic conduction and matches the relative humidity
of the hydrogel to the average ambient relative humidity. The butyl rubber
coating prevents the loss and gain of water due to the daily fluctuation of
ambient relative humidity. We develop the chemistry of dip-coating the butyl
rubber onto the hydrogel, using silanes to achieve both the cross-link of the
butyl rubber and the adhesion between the butyl rubber and the hydrogel. We test
the endurance of the conductor by soaking it in detergent while stretching it
cyclically and by machine-washing it. The loss of water and salt is minimal. It
is hoped that these conductors open applications in healthcare, entertainment,
and fashion.
PMID- 28696091
TI - Enhanced Osseointegration of Porous Titanium Modified with Zeolitic Imidazolate
Framework-8.
AB - Nanoscale zeolitic imidazolate framework-8 (ZIF-8)-modified titanium (ZIF-8@AHT)
can enhance osteogenesis in vitro. In this study, we systematically and
quantitatively examined the effects of ZIF-8@AHT on osteogenesis, and
investigated its ability to form bone in vivo. First, we coated various
quantities of nanoscale ZIF-8 crystals on alkali- and heat-treated titanium (AHT)
by controlling the concentration of the synthesis solution. We then characterized
the ZIF-8@AHT materials using scanning electron microscopy (SEM), powder X-ray
diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), and
determination of the sessile drop contact angle. To illustrate the combined
effects of micro/nanotopography and ZIF-8@AHT composition on bone regeneration,
we cultured MC3T3-E1 preosteoblast cells on various titanium substrates in vitro
by setting pure titanium (Ti) and AHT as control groups. The ZIF-8@AHTs enhanced
cell bioactivity compared with AHT and Ti, as evidenced by increased
extracellular matrix (ECM) mineralization, collagen secretion and the upregulated
expression of osteogenic genes (Alp, Col1, Opg, and Runx2) and osteogenesis
related proteins (ALP and OPG). ZIF-8@AHT-1/8 exhibited better osteogenic
activity compared with the other ZIF-8@AHT groups investigated. We subsequently
inserted Ti, AHT, and ZIF-8@AHT-1/8 implants into the healed first molars (M1s)
of mice, and found that ZIF-8@AHT-1/8 also promoted osseointegration at the bone
implant interface. These results suggest that ZIF-8@AHT-1/8 has great potential
for practical application in implant modification.
PMID- 28696092
TI - Synthesis of Mesoporous Co2+-Doped TiO2 Nanodisks Derived from Metal Organic
Frameworks with Improved Sodium Storage Performance.
AB - TiO2 is a most promising anode candidate for rechargeable Na-ion batteries (NIBs)
because of its appropriate working voltage, low cost, and superior structural
stability during chage/discharge process. Nevertheless, it suffers from
intrinsically low electrical conductivity. Herein, we report an in situ synthesis
of Co2+-doped TiO2 through the thermal treatment of metal organic frameworks
precursors of MIL-125(Ti)-Co as a superior anode material for NIBs. The Co2+
doped TiO2 possesses uniform nanodisk morphology, a large surface area and
mesoporous structure with narrow pore distribution. The reversible capacity,
Coulombic efficiency (CE) and rate capability can be improved by Co2+ doping in
mesoporous TiO2 anode. Co2+-doped mesoporous TiO2 nanodisks exhibited a high
reversible capacity of 232 mAhg-1 at 0.1 Ag1-, good rate capability and cycling
stability with a stable capacity of about 140 mAhg-1 at 0.5 Ag1- after 500
cycles. The enhanced Na-ion storage performance could be due to the increased
electrical conductivity revealed by Kelvin probe force microscopy measurements.
PMID- 28696093
TI - Introducing Ratiometric Fluorescence to MnO2 Nanosheet-Based Biosensing: A
Simple, Label-Free Ratiometric Fluorescent Sensor Programmed by Cascade Logic
Circuit for Ultrasensitive GSH Detection.
AB - Glutathione (GSH) plays crucial roles in various biological functions, the level
alterations of which have been linked to varieties of diseases. Herein, we for
the first time expanded the application of oxidase-like property of MnO2
nanosheet (MnO2 NS) to fluorescent substrates of peroxidase. Different from
previously reported fluorescent quenching phenomena, we found that MnO2 NS could
not only largely quench the fluorescence of highly fluorescent Scopoletin (SC)
but also surprisingly enhance that of nonfluorescent Amplex Red (AR) via
oxidation reaction. If MnO2 NS is premixed with GSH, it will be reduced to Mn2+
and lose the oxidase-like property, accompanied by subsequent increase in SC's
fluorescence and decrease in AR's. On the basis of the above mechanism, we
construct the first MnO2 NS-based ratiometric fluorescent sensor for
ultrasensitive and selective detection of GSH. Notably, this ratiometric sensor
is programmed by the cascade logic circuit (an INHIBIT gate cascade with a 1 to 2
decoder). And a linear relationship between ratiometric fluorescent intensities
of the two substrates and logarithmic values of GSH's concentrations is obtained.
The detection limit of GSH is as low as 6.7 nM, which is much lower than previous
ratiometric fluorescent sensors, and the lowest MnO2 NS-based fluorescent GSH
sensor reported so far. Furthermore, this sensor is simple, label-free, and low
cost; it also presents excellent applicability in human serum samples.
PMID- 28696094
TI - High-Rate Assembly of Nanomaterials on Insulating Surfaces Using Electro-Fluidic
Directed Assembly.
AB - Conductive or semiconducting nanomaterials-based applications such as electronics
and sensors often require direct placement of such nanomaterials on insulating
surfaces. Most fluidic-based directed assembly techniques on insulating surfaces
utilize capillary force and evaporation but are diffusion limited and slow.
Electrophoretic-based assembly, on the other hand, is fast but can only be
utilized for assembly on a conductive surface. Here, we present a directed
assembly technique that enables rapid assembly of nanomaterials on insulating
surfaces. The approach leverages and combines fluidic and electrophoretic
assembly by applying the electric field through an insulating surface via a
conductive film underneath. The approach (called electro-fluidic) yields an
assembly process that is 2 orders of magnitude faster compared to fluidic
assembly. By understanding the forces on the assembly process, we have
demonstrated the controlled assembly of various types of nanomaterials that are
conducting, semiconducting, and insulating including nanoparticles and single
walled carbon nanotubes on insulating rigid and flexible substrates. The
presented approach shows great promise for making practical devices in
miniaturized sensors and flexible electronics.
PMID- 28696095
TI - DT-Diaphorase as a Bifunctional Enzyme Label That Allows Rapid Enzymatic
Amplification and Electrochemical Redox Cycling.
AB - The most common enzyme labels in enzyme-linked immunosorbent assays are alkaline
phosphatase and horseradish peroxidase, which, however, have some limitations for
use in electrochemical immunosensors. This Article reports that the small and
thermostable DT-diaphorase (DT-D) and electrochemically inactive 4-nitroso-1
naphthol (4-NO-1-N) can be used as a bifunctional enzyme label and a rapidly
reacting substrate, respectively, for electrochemical immunosensors. This enzyme
substrate combination allows high signal amplification via rapid enzymatic
amplification and electrochemical redox cycling. DT-D can convert an
electrochemically inactive nitroso or nitro compound into an electrochemically
active amine compound, which can then be involved in electrochemical-chemical
(EC) and electrochemical-enzymatic (EN) redox cycling. Six nitroso and nitro
compounds are tested in terms of signal-to-background ratio. Among them, 4-NO-1-N
exhibits the highest signal-to-background ratio. The electrochemical immunosensor
using DT-D and 4-NO-1-N detects parathyroid hormone (PTH) in phosphate-buffered
saline containing bovine serum albumin over a wide range of concentrations with a
low detection limit of 2 pg/mL. When the PTH concentration in clinical serum
samples is measured using the developed immunosensor, the calculated
concentrations are in good agreement with the concentrations obtained using a
commercial instrument. Thus, the use of DT-D as an enzyme label is highly
promising for sensitive electrochemical detection and point-of-care testing.
PMID- 28696096
TI - Potassium and Zeolitic Structure Modified Ultra-microporous Adsorbent Materials
from a Renewable Feedstock with Favorable Surface Chemistry for CO2 Capture.
AB - Novel hierarchically structured microporous biocarbons with exceptionally high
capacities for CO2 capture have been synthesized from the abundant agricultural
waste of rice husk (RH), using a facile methodology that effectively integrated
carbonization, activation, and potassium intercalation into a one-step process.
Textural characterization demonstrates that the synthesized biocarbons exhibit
exceedingly high ultra-microporosity accounting for up to 95% of total porosity
mainly as a result of the naturally occurring silicon compounds within the RH
molecular framework structures. With a modest surface area of up to 1035 m2/g and
a total pore volume of 0.43 cm3/g, the best performing RH carbon has shown
exceptionally high and fully reversible CO2 uptake capacity of 2.0 mmol/g at 25
degrees C and a CO2 partial pressure of 0.15 bar, which represents one of the
highest uptakes ever reported for both carbon and MOF materials usually prepared
from using cost-prohibitive precursor materials with cumbersome methodologies. It
has been found that up to 50% of the total CO2 uptake is attributable to the
unique surface chemistry of the RH carbons, which appears to be dominated by the
enhanced formation of extra-framework potassium cations owing to the exceedingly
high levels of ultra-microporosity and the presence of zeolitic structures
incorporated within the carbon matrices. Characterizations by EDX element
mapping, XPS, and heat of adsorption measurements confirm the existence of a
range of zeolitic structures, which essentially transforms the RH carbons into a
kind of zeolite-carbon nanocomposite material with strong surface affinity for
CO2.
PMID- 28696097
TI - Chemical Reactions of Molecules Promoted and Simultaneously Imaged by the
Electron Beam in Transmission Electron Microscopy.
AB - The main objective of this Account is to assess the challenges of transmission
electron microscopy (TEM) of molecules, based on over 15 years of our work in
this field, and to outline the opportunities in studying chemical reactions under
the electron beam (e-beam). During TEM imaging of an individual molecule adsorbed
on an atomically thin substrate, such as graphene or a carbon nanotube, the e
beam transfers kinetic energy to atoms of the molecule, displacing them from
equilibrium positions. Impact of the e-beam triggers bond dissociation and
various chemical reactions which can be imaged concurrently with their activation
by the e-beam and can be presented as stop-frame movies. This experimental
approach, which we term ChemTEM, harnesses energy transferred from the e-beam to
the molecule via direct interactions with the atomic nuclei, enabling accurate
predictions of bond dissociation events and control of the type and rate of
chemical reactions. Elemental composition and structure of the reactant molecules
as well as the operating conditions of TEM (particularly the energy of the e
beam) determine the product formed in ChemTEM processes, while the e-beam dose
rate controls the reaction rate. Because the e-beam of TEM acts simultaneously as
a source of energy for the reaction and as an imaging tool monitoring the same
reaction, ChemTEM reveals atomic-level chemical information, such as pathways of
reactions imaged for individual molecules, step-by-step and in real time;
structures of illusive reaction intermediates; and direct comparison of catalytic
activity of different transition metals filmed with atomic resolution. Chemical
transformations in ChemTEM often lead to previously unforeseen products,
demonstrating the potential of this method to become not only an analytical tool
for studying reactions, but also a powerful instrument for discovery of materials
that can be synthesized on preparative scale.
PMID- 28696098
TI - Enhanced Binding Affinity via Destabilization of the Unbound State: A Millisecond
Hydrogen-Deuterium Exchange Study of the Interaction between p53 and a Pleckstrin
Homology Domain.
AB - The incorporation of intrinsically disordered domains enables proteins to engage
a wide variety of targets, with phosphorylation often modulating target
specificity and affinity. Although phosphorylation can clearly act as a chemical
driver of complexation in structured proteins, e.g., by abrogating or permitting
new charge-charge interactions, the basis for enhancement of the hydrophobically
driven interactions that are typical of disordered protein-target complexation is
less clear. To determine how phosphorylation can positively impact target
recruitment in disordered domains, we have examined the interaction between the
disordered N-terminal transactivation domain (TAD) of p53 and the pleckstrin
homology (PH) domain of p62. Using time-resolved electrospray ionization with
hydrogen-deuterium exchange, we demonstrate that phosphorylation has little
effect on the conformation of the p53 TAD when it is bound to the PH domain but
instead increases the degree of conformational disorder in the unbound state. We
propose that this increase in the degree of disorder creates a wider free energy
gap between the free and bound states, providing a target-independent mechanism
for enhanced binding when the phosphorylated and unphosphorylated p53-target
complexes have similar free energies.
PMID- 28696099
TI - Activatable QD-Based Near-Infrared Fluorescence Probe for Sensitive Detection and
Imaging of DNA.
AB - Accurate detection of DNA is essential for the precise diagnosis of diseases.
Here we report an activatable near-infrared (NIR) fluorescence nanoprobe (QD-Al
GFLX) composed of NIR quantum dots (QDs) and Al(III)-gatifloxacin (Al-GFLX)
complexes for the sensitive detection of double-stranded DNA (dsDNA) both in
aqueous solution and in living cells. We demonstrated that the initial strong NIR
fluorescence of QDs in QD-Al-GFLX was quenched by the Al-GFLX complex via a
photoinduced electron transfer (PET) mechanism. Upon interaction with dsDNA, the
high binding affinity between dsDNA and Al-GFLX complex could trigger QD-Al-GFLX
dissociation, which could eliminate the PET process, resulting in significant
enhancement of NIR fluorescence. QD-Al-GFLX was sensitive and specific to detect
dsDNA in aqueous solution, with a detection limit of 6.83 ng/mL. The subsequent
fluorescence imaging revealed that QD-Al-GFLX holds a high ability to enter into
live cells, generating strong NIR fluorescence capable of reporting on dsDNA
levels. This study highlighted the potential of using QD-Al-GFLX nanoprobe for
the real-time detection and imaging of dsDNA in living cells.
PMID- 28696100
TI - Thermosensitive Liposomal Codelivery of HSA-Paclitaxel and HSA-Ellagic Acid
Complexes for Enhanced Drug Perfusion and Efficacy Against Pancreatic Cancer.
AB - Fibrotic stroma and tumor-promoting pancreatic stellate cells (PSCs), critical
characters in the pancreatic ductal adenocarcinoma (PDA) microenvironment,
promote a tumor-facilitating environment that simultaneously prevents drug
penetration into tumor foci and stimulates tumor growth. Nab-PTX, a human serum
albumin (HSA) nanoparticle of paclitaxel (PTX), indicates enhanced matrix
penetration in PDA probably due to its small size in vivo and high affinity of
HSA with secreted protein acidic and rich in cysteine (SPARC), overexpressed in
the PDA stroma. However, this HSA nanoparticle shows poor drug blood retention
because of its weak colloidal stability in vivo, thus resulting in insufficient
drug accumulation within tumor. Encapsulating HSA nanoparticles into the internal
aqueous phase of ordinary liposomes improves their blood retention and the
following tumor accumulation, but the large 200 nm size and shielding of HSA in
the interior might make it difficult for this hybrid nanomedicine to penetrate
the fibrotic PDA matrix and promote bioavailability of the payload. In our
current work, we prepared ~9 nm HSA complexes with an antitumor drug (PTX) and an
anti-PSC drug (ellagic acid, EA), and these two HSA-drug complexes were further
coencapsulated into thermosensitive liposomes (TSLs). This nanomedicine was named
TSL/HSA-PE. The use of TSL/HSA-PE could improve drug blood retention, and upon
reaching locally heated tumors, these TSLs can rapidly release their payloads
(HSA-drug complexes) to facilitate their further tumor accumulation and matrix
penetration. With superior tumor accumulation, impressive matrix penetration, and
simultaneous action upon tumor cells and PSCs to disrupt PSCs-PDA interaction,
TSL/HSA-PE treatment combined with heat exhibited strong tumor growth inhibition
and apoptosis in vivo.
PMID- 28696101
TI - Systematic First-Principles Study of Binary Metal Hydrides.
AB - First-principles calculations were systematically performed for 31 binary metal
hydrogen (M-H) systems on a set of 30 potential crystal structures selected on
the basis of experimental data and possible interstitial sites. For each M-H
system, the calculated enthalpies of formation were represented as functions of H
composition. The zero-point energy correction was considered for the most stable
hydrides via additional harmonic phonon calculations. The sequence of stable
hydrides (ground-state) given by the convex hull was found in satisfactory
agreement with the experimental data. In addition, new high pressure dihydrides
and trihydrides were predicted, providing orientations for new materials
synthesis. The overall results provide a global overview of hydride relative
stabilities and relevant input data for thermodynamic modeling methods.
PMID- 28696102
TI - Release and Gas-Particle Partitioning Behaviors of Short-Chain Chlorinated
Paraffins (SCCPs) During the Thermal Treatment of Polyvinyl Chloride Flooring.
AB - Chlorinated paraffin (CP) mixture is a common additive in polyvinyl chloride
(PVC) products as a plasticizer and flame retardant. During the PVC plastic life
cycle, intentional or incidental thermal processes inevitably cause an abrupt
release of short-chain CPs (SCCPs). In this study, the thermal processing of PVC
plastics was simulated by heating PVC flooring at 100-200 degrees C in a
chamber. The 1 h thermal treatment caused the release of 1.9-10.7% of the
embedded SCCPs. A developed emission model indicated that SCCP release was mainly
controlled by material-gas partitioning at 100 degrees C. However, release
control tended to be subjected to material-phase diffusion above 150 degrees C,
especially for SCCP congeners with shorter carbon-chain lengths. A cascade
impactor (NanoMoudi) was used to collect particles of different sizes and gas
phase SCCPs. The elevated temperature resulted in a higher partition of SCCPs
from the gas-phase to particle-phase. SCCPs were not strongly inclined to form
aerosol particles by nucleation, and less present in the Aitken mode particles.
Junge-Pankow adsorption model well fitted the partitioning of SCCPs between the
gas-phase and accumulation mode particles. Inhalation exposure estimation
indicated that PVC processing and recycling workers could face a considerably
high risk for exposure to SCCPs.
PMID- 28696103
TI - Photodriven Oxygen Removal via Chromophore-Mediated Singlet Oxygen Sensitization
and Chemical Capture.
AB - We report a general, photochemical method for the rapid deoxygenation of organic
solvents and aqueous solutions via visible light excitation of transition metal
chromophores (TMCs) in the presence of singlet oxygen scavenging substrates.
Either 2,5-dimethylfuran or an amino acid (histidine or tryptophan methyl ester)
was used as the substrate in conjunction with an iridium or ruthenium TMC in
toluene, acetonitrile, or water. This behavior is described for solutions with
chromophore concentrations that are pertinent for both luminescence and transient
absorption spectroscopies. These results consistently produce TMC lifetimes
comparable to those measured using traditional inert gas sparging and freeze-pump
thaw techniques. This method has the added benefits of providing long-term
stability (days to months); economical preparation due to use of inexpensive,
commercially available oxygen scrubbing substrates; and negligible size and
weight footprints compared to traditional methods. Furthermore, attainment of
dissolved [O2] < 50 MUM makes this method relevant to any solution application
requiring low dissolved oxygen concentration in solution, provided that the
oxygenated substrate does not interfere with the intended chemical process.
PMID- 28696104
TI - Wide-Acidity-Range pH Fluorescence Probes for Evaluation of Acidification in
Mitochondria and Digestive Tract Mucosa.
AB - The cells control their pH change in a very accurate range. pH plays important
roles in cell autophagy and apoptosis. Previous evidence implies that the
internal milieu of a tumor is acidified. Although the acidification in cells is
investigated, the biological effects from multiple stimulating factors under the
complex intracellular environment have not been thoroughly elaborated yet.
Currently, there are few pH probes that perform in a wide acidity range, and a
probe that is capable of measuring a wide pH range needs to be developed. Herein,
we report two new fluorescent probes (BHNBD and CM-BHNBD) for the detection of
mitochondrial and intramucosal acidification. The two probes respond to pH via an
H+-driven TICT (twist intramolecular charge transfer) mechanism, and they can
linearly report pH within a wide pH range: 7.00-2.00 following ~148-fold
fluorescence increase. The two probes also possess excellent membrane
permeability, good photostability, and negligible cytotoxicity. The probes are
successfully applied for quantifying the acidification in HeLa cells under the
simultaneous stimulation of nutrient deprivation and oxidative stress. Our
results demonstrate that the mitochondrial pH is in a dynamic fluctuating state
during the acidification process, which suggests a potential cross-talk effect
between cell autophagy and apoptosis. We also use the probes for quantifying the
intramucosal pH variation in stomach and esophagus via manipulating cellular
proton pump. The development of our probes is potentially expected to be used to
monitor the intracellular/intramucosal acidification for biomedical research.
PMID- 28696105
TI - Visible and Near-Infrared Emission from Lanthanoid beta-Triketonate Assemblies
Incorporating Cesium Cations.
AB - The reaction of the beta-triketonate ligands tris(4-methylbenzoyl)methanide and
tribenzoylmethanide with the trivalent lanthanoids Eu3+, Er3+, and Yb3+ in the
presence of Cs+ afforded polymeric structures where the repeating units are
represented by bimetallic tetranuclear assemblies of formulation {[Ln(Cs)(beta
triketonate)4]2}n. The only exception is the structure formed by the reaction of
tris(4-methylbenzoyl)methanide, Yb3+, and Cs+, which yielded a polymeric assembly
where the repeating units are mononuclear Yb3+ complexes bridged by Cs+ cations.
Photophysical measurements on the obtained materials confirmed efficient
sensitization from the ligand excited states to the 4f* excited states of the
three lanthanoids. According to transient absorption data, Er3+ and Yb3+ are
sensitized via energy transfer from the triplet state of the beta-triketonate
ligands. On the other hand, energy transfer to Eu3+ seems to occur via an
alternative pathway, possibly directly via the singlet state or through ligand to
metal charge transfer states. The emission measurements confirm efficient
sensitization for all three lanthanoids and bright near-infrared emission for
Er3+ and Yb3+, a characteristic that seems to be linked to the specific chemical
structure of the beta-triketonate ligands.
PMID- 28696106
TI - Carotenoids and Carotenoid Esters of Red and Yellow Physalis (Physalis alkekengi
L. and P. pubescens L.) Fruits and Calyces.
AB - Carotenoid profiles of fruits and calyces of red (Physalis alkekengi L.) and
yellow (P. pubescens L.) Physalis were characterized by HPLC-DAD-APCI-MSn.
Altogether 69 carotenoids were detected in red Physalis, thereof, 45 were
identified. In yellow Physalis, 40 carotenoids were detected and 33 were
identified. Zeaxanthin esters with various fatty acids were found to be the most
abundant carotenoids in red Physalis, accounting for 51-63% of total carotenoids,
followed by beta-cryptoxanthin esters (16-24%). In yellow Physalis, mainly free
carotenoids such as lutein and beta-carotene were found. Total carotenoid
contents ranged between 19.8 and 21.6 mg/100 g fresh red Physalis fruits and 1.28
1.38 mg/100 g fresh yellow Physalis fruits, demonstrating that Physalis fruits
are rich sources of dietary carotenoids. Yellow Physalis calyces contained only
153-306 MUg carotenoids/g dry weight, while those of red Physalis contained
substantially higher amounts (14.6-17.6 mg/g dry weight), thus possibly
exhibiting great potential as a natural source for commercial zeaxanthin
extraction.
PMID- 28696107
TI - Oxidation State of Capping Agent Affects Spatial Reactivity on Gold Nanorods.
AB - Despite enormous progress toward controlling the shapes and surface chemistry of
colloidal nanoparticles, spatial control of nanoparticle surface chemistry
remains a major challenge. In recent years, there have been tantalizing reports
demonstrating anisotropic silica coating of gold nanorods in which silica is
deposited only on the sides by functionalizing the nanorods with poly(ethylene
glycol) methyl ether thiol (PEG-thiol) prior to silica coating, but such results
have been difficult to reproduce. We report that the oxidation state of PEG-thiol
is key to anisotropic silica coating, with the disulfide, not the thiol, leading
to side silica coating. PEG-disulfide appears to selectively functionalize the
ends of gold nanorods, and robust methods are developed to reliably deposit side
silica shells on PEG-disulfide functionalized gold nanorods.
PMID- 28696108
TI - Incorporating Fast Protein Dynamics into Enzyme Design: A Proposed Mutant
Aromatic Amine Dehydrogenase.
AB - In recent years, there has been encouraging progress in the engineering of
enzymes that are designed to catalyze reactions not accelerated by natural
enzymes. We tested the possibility of reengineering an existing enzyme by
introducing a fast protein motion that couples to the reaction. Aromatic amine
dehydrogenase is a system that has been shown to use a fast substrate motion as
part of the reaction mechanism. We identified a mutation that preserves this fast
motion but also introduces a favorable fast motion near the active site that did
not exist in the native enzyme. Transition path sampling was used for the
analysis of the atomic details of the mechanism.
PMID- 28696109
TI - Computational and Experimental Studies on the Effects of Monomer Planarity on
Covalent Organic Framework Formation.
AB - We report the synthesis of one new boronate ester-based covalent organic
framework (COF) and two new covalent organic polymers (COPs) made with
fluoranthene-containing monomers and hexahydroxytriphenylene. The structure of
the monomer heavily influences whether this material forms a highly ordered
mesoporous material (COF) or an amorphous, microporous material (COP). The
synthesis of the fluoranthene monomers was carried out using a divergent strategy
that allows for systematic structural variation and the ability to conduct a
careful structure-function study. We found that small structural variations in
the monomers dramatically affected the crystallinity, surface area, pore
structure, and luminescence properties of the polymers. While each of the
monomers contains the same fluoranthene core, the resultant pore sizes range from
microporous (10 A) to mesoporous (37 A), with surface areas ranging from ~500 to
1200 m2/g. To help explain how these small structural differences can have such a
large effect, we carried out a series of molecular dynamics simulations on the
polymers to obtain information with atomic-scale resolution on how the monomer
structure affects non-covalent COF layer stacking.
PMID- 28696110
TI - A Redox-Active Cascade Precursor: Isolation of a Zwitterionic Triphenylphosphonio
Hydrazyl Radical and an Indazolo-Indazole Derivative.
AB - A redox-active [ML] unit (M = CoII and MnII; LH2 = N'-(1,4-dioxo-1,4
dihydronaphthalen-2-yl)benzohydrazide) defined as a cascade precursor that
undergoes a multicomponent redox reaction comprising of a C-N bond formation,
tautomerization, oxidation, C-C coupling, demetalation, and affording 6,14
dibenzoylbenzo[f]benzo[5,6]indazolo[3a,3-c]indazole-5,8,13,16-tetraone (IndL2) is
reported. Conversion of LH2 -> IndL2 in air is overall a (6H++6e) oxidation
reaction, and it opens a route for the syntheses of bioactive diarylindazolo[3a,3
c]indazole derivatives. The reaction occurs via a radical coupling reaction, and
the radical intermediate was isolated as a triphenylphosphonio adduct. In
presence of PPh3 the [ML] unit promotes a reaction that involves a C-P bond
formation, tautomerization, and oxidation to yield a stable zwitterionic
triphenylphosphonio-hydrazyl radical (PPh3L+/-*). Conversion of LH2 -> PPh3L+/-*
is a (3H++3e) oxidation reaction. To authenticate the [ML] unit, in addition to
the IndL2, a zinc(II) complex, [(L3)ZnII(H2O)Cl].2MeOH (1.2MeOH), was
successfully isolated (L3H = a pyridazine derivative of 1,4 naphthoquinone) from
a reaction of LH2 with hydrated ZnCl2. Conversion of 3LH2 -> 1 is also a
multicomponent (6H++6e) oxidation reaction promoted by zinc(II) ion via a radical
intermediate. Facile oxidation of [L2-] to [L*-] that was considered as an
intermediate of these conversions was confirmed by isolating a 1,4 naphthoquinone
benzhydrazyl radical (LH*) complex, [(LH*)ZnII(H2O)Cl2] (2H*). The intermediates
of LH2 -> IndL2, LH2 -> PPh3L+/-*, and 3LH2 -> 1 conversions were analyzed by
electrospray ionization mass spectroscopy. The molecular and electronic
structures of PPh3L+/-*, IndL2, 1.2MeOH, and 2H* were confirmed by single-crystal
X-ray crystallography, electron paramagnetic resonance spectroscopy, and density
functional theory calculations.
PMID- 28696111
TI - Face-Dependent Solvent Adsorption: A Comparative Study on the Interfaces of HMX
Crystal with Three Solvents.
AB - To understand the crystal-solvent interfacial interactions on the molecular
scale, the interfaces between three solvents, that is, acetone, gamma
butyrolactone, and cyclohexanone, and three growth faces of 1,3,5,7-tetranitro
1,3,5,7-tetrazocane (HMX) crystal have been investigated with the aid of
theoretical chemistry. The results show that the structural features of crystal
faces play a critical role in the energetic, structural, and dynamic properties
at the interfaces. For each solvent, the same change trend of some properties
among the three faces of HMX crystal is observed, including adsorption affinity,
local mass density, and solvent diffusion. For example, the rate of solvent
diffusion at the three faces ranks as (011) > (110) > (020) regardless of solvent
species. This can be attributed to the similar adsorption sites for solvent
incorporation at the same face, which are concentrated at the cavities formed by
surficial HMX molecules.
PMID- 28696113
TI - Confined Pyrolysis within Metal-Organic Frameworks To Form Uniform Ru3 Clusters
for Efficient Oxidation of Alcohols.
AB - Here we report a novel approach to synthesize atomically dispersed uniform
clusters via a cage-separated precursor preselection and pyrolysis strategy. To
illustrate this strategy, well-defined Ru3(CO)12 was separated as a precursor by
suitable molecular-scale cages of zeolitic imidazolate frameworks (ZIFs). After
thermal treatment under confinement in the cages, uniform Ru3 clusters stabilized
by nitrogen species (Ru3/CN) were obtained. Importantly, we found that Ru3/CN
exhibits excellent catalytic activity (100% conversion), high chemoselectivity
(100% for 2-aminobenzaldehyde), and significantly high turnover frequency (TOF)
for oxidation of 2-aminobenzyl alcohol. The TOF of Ru3/CN (4320 h-1) is about 23
times higher than that of small-sized (ca. 2.5 nm) Ru particles (TOF = 184 h-1).
This striking difference is attributed to a disparity in the interaction between
Ru species and adsorbed reactants.
PMID- 28696114
TI - Total Synthesis and Antibacterial Investigation of Plusbacin A3.
AB - The total synthesis of plusbacin A3 (1) has been accomplished using a solvent
dependent diastereodivergent Joullie-Ugi three-component reaction (JU-3CR) as a
key step. Two trans-3-hydroxy-l-proline residues were constructed by combining
the JU-3CR with a convertible isocyanide strategy. Subsequent peptide coupling
and macrolactamization afforded plusbacin A3. Investigating the antibacterial
activity of 1 compared with that of its dideoxy analogue revealed that the threo
beta-hydroxyaspartic acid residues are essential for antibacterial activity.
Notably, there is a low potential for the development of resistance in S. aureus
against plusbacin A3.
PMID- 28696116
TI - Total Synthesis and Structural Revision of Aeruginosin KT608A.
AB - The synthesis of the presumed structure of aeruginosin KT608A was accomplished
for the first time. The unusual d-diepi-Choi core was prepared from tyrosine via
C-H activation and heterogeneous hydrogenation. Due to differences in the
spectral data of synthetic and natural samples, a revised structure featuring l
diepi-Choi was proposed, which was synthesized and confirmed to be identical. On
the basis of these findings, revised structures for six additional aeruginosins
(KT608B, KT650, GH553, DA495A, DA511, and KB676) are presented.
PMID- 28696115
TI - Discovery of a Benzamide Derivative That Protects Pancreatic beta-Cells against
Endoplasmic Reticulum Stress.
AB - Endoplasmic reticulum (ER) stress-mediated pancreatic insulin-producing beta-cell
dysfunction and death are critical elements in the onset and progression of both
type 1 and type 2 diabetes. Here, through cell-based high throughput screening we
identified benzamide derivatives as a novel class of beta-cell protective agents
against ER stress-induced dysfunction and death. Through structure-activity
relationship optimization, a 3-(N-piperidinyl)methylbenzamide derivative 13d
markedly protects beta-cells against ER stress-induced dysfunction and death with
near 100% maximum rescue activity and an EC50 of 0.032 MUM. Compound 13d
alleviates ER stress in beta-cells by suppressing ER stress-mediated activation
of all three branches of unfolded protein response (UPR) and apoptotic genes.
Finally, we show that 13d significantly lowers blood glucose levels and increases
concomitant beta-cell survival and number in a streptozotocin-induced diabetic
mouse model. Identification of beta-cell-protective small molecules against ER
stress provides a new promising modality for the treatment of diabetes.
PMID- 28696117
TI - Catalytic Cycle of Haloalkane Dehalogenases Toward Unnatural Substrates Explored
by Computational Modeling.
AB - The anthropogenic toxic compound 1,2,3-trichloropropane is poorly degradable by
natural enzymes. We have previously constructed the haloalkane dehalogenase
DhaA31 by focused directed evolution ( Pavlova, M. et al. Nat. Chem. Biol. 2009 ,
5 , 727 - 733 ), which is 32 times more active than the wild-type enzyme and is
currently the most active variant known against that substrate. Recent evidence
has shown that the structural basis responsible for the higher activity of DhaA31
was poorly understood. Here we have undertaken a comprehensive computational
study of the main steps involved in the biocatalytic hydrolysis of 1,2,3
trichloropropane to decipher the structural basis for such enhancements. Using
molecular dynamics and quantum mechanics approaches we have surveyed (i) the
substrate binding, (ii) the formation of the reactive complex, (iii) the chemical
step, and (iv) the release of the products. We showed that the binding of the
substrate and its transport through the molecular tunnel to the active site is a
relatively fast process. The cleavage of the carbon-halogen bond was previously
identified as the rate-limiting step in the wild-type. Here we demonstrate that
this step was enhanced in DhaA31 due to a significantly higher number of reactive
configurations of the substrate and a decrease of the energy barrier to the SN2
reaction. C176Y and V245F were identified as the key mutations responsible for
most of those improvements. The release of the alcohol product was found to be
the rate-limiting step in DhaA31 primarily due to the C176Y mutation. Mutational
dissection of DhaA31 and kinetic analysis of the intermediate mutants confirmed
the theoretical observations. Overall, our comprehensive computational approach
has unveiled mechanistic details of the catalytic cycle which will enable a
balanced design of more efficient enzymes. This approach is applicable to deepen
the biochemical knowledge of a large number of other systems and may contribute
to robust strategies in the development of new biocatalysts.
PMID- 28696118
TI - Fusion of Ultraviolet-Visible and Infrared Transient Absorption Spectroscopy Data
to Model Ultrafast Photoisomerization.
AB - Ultrafast photoisomerization reactions generally start at a higher excited state
with excess of internal vibrational energy and occur via conical intersections.
This leads to ultrafast dynamics which are difficult to investigate with a single
transient absorption spectroscopy technique, be it in the ultraviolet-visible (UV
vis) or infrared (IR) domain. On one hand, the information available in the UV
vis domain is limited as only slight spectral changes are observed for different
isomers. On the other hand, the interpretation of vibrational spectra is strongly
hindered by intramolecular relaxation and vibrational cooling. These limitations
can be circumvented by fusing UV-vis and IR transient absorption spectroscopy
data in a multiset multivariate curve resolution analysis. We apply this approach
to describe the spectrodynamics of the ultrafast cis-trans photoisomerization
around the C-N double bond observed for aromatic Schiff bases. Twisted
intermediate states could be elucidated, and isomerization was shown to occur
through a continuous complete rotation. More broadly, data fusion can be used to
rationalize a vast range of ultrafast photoisomerization processes of interest in
photochemistry.
PMID- 28696119
TI - Organocatalytic Para-Selective Amination of Phenols with Iminoquinone
Monoacetals.
AB - A highly selective para C-H amination of unprotected phenols with iminoquinone
acetals was realized, giving the functional phenols in good to excellent yields.
Overall, this transformation is operationally simple, proceeds with readily
available phenols, and has wide substrate scope and low catalyst loading. The
biarylamine product is stochastically formed via [5,5]-sigmatropic rearrangement
of a mixed acetal species which is generated in situ under the reaction
conditions.
PMID- 28696120
TI - One-Pot Method for the Synthesis of 2,5-Unsubstituted
Pyrrolidino[3',4':1,9]fullerenes.
AB - A new, efficient process has been developed for the preparation of 2,5
unsubstituted pyrrolidino[3',4':1,9]fullerenes by the Ti(O-i-Pr)4-promoted
reaction of fullerene C60 with 1,3,5-perhydrotriazines generated in situ upon the
reaction of primary alkyl- and benzylamines with paraformaldehyde and EtMgBr.
PMID- 28696121
TI - Transition-Metal-Free Poly(thiazolium) Iodide/1,8-Diazabicyclo[5.4.0]undec-7
ene/Phenazine-Catalyzed Esterification of Aldehydes with Alcohols.
AB - Poly(3,4-dimethyl-5-vinylthiazolium) iodide was used as a polymer precatalyst in
the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) and phenazine for the
oxidative esterification of aldehydes with alcohols. Selective functionalization
of OH groups was achieved in the presence of NH2 groups. The poly(thiazolium)
iodide/DBU/phenazine system exhibited excellent catalytic activity and could be
reused five times without loss of activity.
PMID- 28696122
TI - Synthesis of Unsymmetrical Tertiary Phosphine Oxides via Sequential Substitution
Reaction of Phosphonic Acid Dithioesters with Grignard Reagents.
AB - A facile synthetic method for unsymmetrical tertiary phosphine oxides is
reported. Sequential treatment of phosphonodithioic acid S,S-di(p-tolyl) esters
with two Grignard reagents enabled the stepwise introduction of different carbon
substituents on the phosphorus atom. The chemical stability of dithioesters and
monosubstituted thioesters has enhanced the utility of this method, rendering a
wide range of organophosphorus compounds easily available.
PMID- 28696123
TI - Determining the True Optical Gap in a High-Performance Organic Photovoltaic
Polymer Using Single-Molecule Spectroscopy.
AB - Low-gap conjugated polymers have enabled an impressive increase in the
efficiencies of organic solar cells, primarily due to their red absorption that
allows harvesting of that part of the solar spectrum. Here we report that the
true optical gap of one prototypical material, PTB7, is in fact at significantly
higher energy than has previously been reported, indicating that the red
absorption utilized in these materials in solar cells is entirely due to chain
aggregation. Using single-molecule spectroscopy we find that PL from isolated
nanoscale aggregates consists of multiple independently emitting chromophores. At
the single-molecule level, however, straight single chains with a high degree of
emission polarization are observed. The PL is found to be ~0.4 eV higher in
energy, with a longer lifetime than the red aggregates, and is attributed to
single chromophores. Our findings indicate that the impressive light-harvesting
abilities of PTB7 in the red spectral region arise solely from chain aggregation.
PMID- 28696124
TI - Visible-Light-Triggered Directly Reductive Arylation of Carbonyl/Iminyl
Derivatives through Photocatalytic PCET.
AB - The first visible-light-mediated radical-radical cross-coupling strategy that
enables the direct arylation of carbonyl/iminyl derivatives in the presence of
Et3N has been realized. Such an atom-economical protocol furnishes a broad scope
of arylation products such as secondary/tertiary alcohols and amines via a PCET
process that facilitates the challenging reduction of C?X (X = O, N). Mechanistic
investigation indicates two photocatalytic redox cycles were involved in the
process, and Et3N was proved to serve as a dual reductant and proton donor.
Moreover, the isolated byproducts and controlled experiments could be considered
as powerful supporting evidence for our hypothesis.
PMID- 28696125
TI - Synthesis of a Glycosylphosphatidylinositol Anchor Derived from Leishmania
donovani That Can Be Functionalized by Cu-Catalyzed Azide-Alkyne Cycloadditions.
AB - A flexible assembly strategy has been developed for the synthesis of Leishmania
donovani GPI anchors that bear a clickable alkyne tag. This strategy is based on
the use of the 2-naphthylmethyl (Nap) ethers and levulinoyl (Lev) ester for
permanent protection of hydroxyls. Removal of seven Nap ethers by 2,3-dichloro
5,6-dicyano-1,4-benzoquinone made it possible to prepare GPIs having an alkyne
functionality that could be modified by Cu(I)-catalyzed [3 + 2] cycloadditions to
install tags for imaging studies.
PMID- 28696126
TI - Suppressing Excimers in H-Aggregates of Perylene Bisimide Folda-Dimer: Role of
Dimer Conformation and Competing Assembly Pathways.
AB - Long-lived excitons in H-aggregates hold great promise for efficient transport of
excitation energy, provided they are not scavenged by structurallly relaxed
excimers. We report solution self-assembly of a perylene bisimide (PBI) folda
dimer that exhibits two distinct kinetic stages: an initial fast assembly leads
to metastable aggregates with large excimer contribution that is followed by a
slower growth of stable, extended H-aggregates free of excimers. Mechanistic
investigations reveal an interplay of two competing aggregation pathways, where
suppression of excimers is directly linked to the crossover from an isodesmic to
cooperative aggregation. How the comeptition between two self-assembly pathways
is influenced by the conformational flexibility of the folda-dimer is also
discussed.
PMID- 28696127
TI - Regioselective 1,2-Diol Rearrangement by Controlling the Loading of BF3.Et2O and
Its Application to the Synthesis of Related Nor-Sesquiterene- and Sesquiterene
Type Marine Natural Products.
AB - The regiocontrolled rearrangement of 1,2-diols has been achieved by controlling
the loading of BF3.Et2O. Its applicability is showcased by the divergent
synthesis of austrodoral, austrodoric acid, and 8-epi-11-nordriman-9-one, as well
as a formal synthesis of siphonodictyal B and liphagal. A new light is shed on
piancol-type rearrangements that will be useful in diversity-oriented synthesis
of related natural products.
PMID- 28696128
TI - Reversal of Enantioselectivity Approach to BINOLs via Single and Dual 2-Naphthol
Activation Modes.
AB - A mechanism-driven enantiodivergent approach to chiral 1,1'-bi-2-naphthols via
catalytic asymmetric oxidative coupling of 2-naphthol derivatives is described
for the first time. By utilizing 2-naphthol derivatives with low oxidation
potential, the substrates were activated by either chiral mononuclear or
dinuclear vanadium(V) catalyst to promote distinctively different asymmetric
reaction pathways: single versus dual substrate activation mechanisms.
PMID- 28696129
TI - Gender dysphoria in Klinefelter's syndrome: three cases.
AB - BACKGROUND: Previous reports have found the incidence of gender dysphoria in
Klinefelter's patients greater than in the general male population. METHODS: A
cohort of patients with gender dysphoria was reviewed. RESULTS: Of the 220
patients with gender dysphoria, three had Klinefelter's syndrome. CONCLUSIONS:
These three reports are further examples of gender dysphoria in Klinefelter's
syndrome. The role of biological factors in gender identity is affirmed. Caution
is urged in prescribing testosterone.
PMID- 28696130
TI - Spectrum of care: Current management of childhood autism spectrum disorder (ASD)
in New Zealand.
AB - OBJECTIVES: The purpose of this research was to compare the current status of
assessment and intervention for New Zealand children and adolescents who have
autism spectrum disorder (ASD) with recommendations outlined in the 2008 New
Zealand ASD Guideline. METHODS: ASD coordinators and New Zealand District Health
Board (DHB) staff working with children and adolescents who have ASD were
electronically surveyed. RESULTS: Responses were received from 32 staff in 17
(85%) surveyed DHBs. Positive findings included the presence of ASD coordinators
in 85% of DHBs, clear pathways for management in 73.1% of DHBs and good
communications between paediatric, psychiatric and educational teams in some DHBs
regions. Areas for improvement included wait times to assessment, access to
longer-term support and intervention for families, and training for staff in ASD
and cultural issues. CONCLUSIONS: Since the launch of the NZ ASD Guidelines,
significant progress has been made. However, further work is needed to ensure
services for children and adolescents with ASD are accessible, well-coordinated
and focussed on both assessment and intervention.
PMID- 28696131
TI - Partial dopamine agonist-induced pathological gambling and impulse-control
deficit on low-dose aripiprazole.
AB - OBJECTIVE: To describe a case of aripiprazole-induced problem gambling and
impulse-control deficit in a gambling-naive patient following commencement of low
dose aripiprazole. METHOD: Case report. RESULTS: This case adds to the literature
on the dopamine partial agonist aripiprazole causing or exacerbating problem
gambling, and extends that literature to low-dose use of aripiprazole in the
gambling naive. CONCLUSIONS: When commencing a patient on aripiprazole the
possibility of emergence of problem gambling and other impulse-control deficits
should be monitored, even in those with no history of similar behaviours and even
on a low dose.
PMID- 28696132
TI - Unlikely reformer: Dr Henry Calvert Barnett (1832-1897).
AB - OBJECTIVE: To provide a brief biography of Western Australian colonial lunacy
superintendent Dr Henry Calvert Barnett. METHOD: A range of primary sources were
consulted. RESULTS: Barnett was a complex man: a caring and forward-thinking
practitioner who had a colourful and turbulent private life. CONCLUSIONS:
Barnett's contribution to mental health service development in Western Australia
was genuine and worthwhile, and should be recognised.
PMID- 28696133
TI - Competitive Binding Investigations and Quantitation in Surface-Enhanced Raman
Spectra of Binary Dye Mixtures.
AB - This research presents a study in surface-enhanced Raman quantitation of dyes
present in mixtures of alizarin and purpurin using standard calibration curves
and Langmuir isotherm calibration models. Investigations of the nature of
competitive adsorption onto silver nanoparticles by centrifugation indicates that
both dyes in the mixture interact with the nanoparticles simultaneously, but only
the stronger adsorbing one is seen to dominate the spectral characteristics.
Calibration can be carried out by careful selection of peaks characteristic to
each dye in the mixture. Comparisons of peak height and peak area calibrations
reveal that peak heights, when selected by the maximum value and accounting for
peak shifts, prove the better model for quantitation. It is also shown that the
microwave nanoparticle synthesis method produces stable nanoparticles with a
shelf-life of at least one year that give very little variation within and
between uses.
PMID- 28696134
TI - Arterial stiffness is associated to cardiorespiratory fitness and body mass index
in young Swedish adults: The Lifestyle, Biomarkers, and Atherosclerosis study.
AB - Background Early changes in the large muscular arteries are already associated
with risk factors as hypertension and obesity in adolescence and young adulthood.
The present study examines the association between arterial stiffness
measurements, pulse wave velocity and augmentation index and lifestyle-related
factors, body composition and cardiorespiratory fitness, in young, healthy,
Swedish adults. Design This study used a population-based cross-sectional sample.
Methods The 834 participants in the study were self-reported healthy, non
smoking, age 18-25 years. Augmentation index and pulse wave velocity were
measured with applanation tonometry. Cardiorespiratory fitness was measured by
ergometer bike test to estimate maximal oxygen uptake. Body mass index (kg/m2)
was calculated and categorised according to classification by the World Health
Organisation. Results Young Swedish adults with obesity and low cardiorespiratory
fitness have significantly higher pulse wave velocity and augmentation index than
non-obese young adults with medium or high cardiorespiratory fitness. The
observed U-shaped association between pulse wave velocity and body mass index
categories in women indicates that it might be more beneficial to be normal
weight than underweight when assessing the arterial stiffness with pulse wave
velocity. The highest mean pulse wave velocity was found in overweight/obese
individuals with low cardiorespiratory fitness. The lowest mean pulse wave
velocity was found in normal weight individuals with high cardiorespiratory
fitness. Cardiorespiratory fitness had a stronger effect than body mass index on
arterial stiffness in multiple regression analyses. Conclusions The inverse
association between cardiorespiratory fitness and arterial stiffness is observed
already in young adults. The study result highlights the importance of high
cardiorespiratory fitness, but also that underweight individuals may be a
possible risk group that needs to be further studied.
PMID- 28696135
TI - Application of Solution-Focused Brief Therapy (SFBT) in individuals after stroke.
AB - OBJECTIVE: To examine the effects of Solution Focused Brief Therapy (SFBT) in
individuals after stroke on self-efficacy, symptoms of depression and anxiety.
DESIGN: Randomized controlled trial. SETTING: Clinic of Adult Neurology of
Medical University of Gdansk and M. Copernicus Pomeranian Traumatology Centre in
Gdansk. SUBJECTS: A total of 62 patients, aged 54.0 +/- 9.6 years. INTERVENTIONS:
They were randomly assigned to one of the two groups: SFBT participating in 10
therapy sessions and control - not participating in any psychotherapy. MAIN
MEASURES: Symptoms of depression and anxiety according to Hospital Anxiety and
Depression Scale, Mini-Mental Adjustment to Cancer (scale originally designed for
cancer patients) and Self-efficacy Scale were examined at baseline of the study
and later in the same time intervals in both groups. RESULTS: The intensity of
depression and anxiety complaints drops in the SFBT group (from 5.0 to 2.0 and
8.0 to 4.0 respectively; both p < .001 Friedman's ANOVA (analysis of variance))
whilst in the control group remains unchanged. In addition to the gradual
reduction of destructive attitudes (from 34.5 to 17.0), the increase in the
number of constructive attitudes (from 42.0 to 50.5) and increased self-efficacy
(from 79.0 to 96.0) was observed after therapy but not in the control group.
CONCLUSIONS: The authors suggest SFBT as a simple, beneficial and inexpensive
method to manage patients after stroke.
PMID- 28696136
TI - Erratum.
PMID- 28696137
TI - Persistence of socioeconomic inequalities in the knowledge of cardiovascular risk
factors five years after coronary angiography.
AB - BACKGROUND: Cardiovascular diseases are important causes of death, morbidity, and
years of potential life lost in most developed countries. AIMS: The purpose of
this study was to assess trends in knowledge of cardiovascular risk factors among
patients five years after coronary angiography and to investigate the impact of
educational level on knowledge level. METHODS: The study included 1289 of 4391
patients admitted for cardiac events in 2008/2009 at the National Institute for
Cardiac Surgery and Interventional Cardiology, Luxembourg. A follow-up study was
conducted by post five years later (2013/2014). Data were obtained from 1837 of
the contacted patients (with 548 reported deaths) (response rate=42%). Logistic
regression models were used to evaluate the association between educational level
and knowledge of cardiovascular risk factors. Educational level was used as a
surrogate for socioeconomic status. RESULTS: In total, 39.9% of patients could
list at least three risk factors in 2013/2014, a much higher percentage than the
8.5% observed during the initial survey. In both sexes, knowledge of
cardiovascular risk factors increased between 2008/2009 and 2013/2014. Patients
with higher educational levels were more likely (odds ratio=2.33, 95% confidence
interval: 1.63-3.34) to cite at least three risk factors than patients with lower
education levels. CONCLUSION: Knowledge level was associated with educational
level, and improved for all educational groups five years after coronary
angiography. Educational differences in knowledge persisted, but the gaps
decreased. Improving knowledge of cardiovascular risk factors among patients with
cardiovascular disease will help increase awareness and promote lifestyle
changes.
PMID- 28696139
TI - Gut microbiome in multiple sclerosis: The players involved and the roles they
play.
AB - The human gut contains trillions of bacteria (microbiome) that play a major role
in maintaining a healthy state for the host. Perturbation of this healthy gut
microbiome might be an important environmental factor in the pathogenesis of
inflammatory autoimmune diseases such as multiple sclerosis (MS). Others and we
have recently reported that MS patients have gut microbial dysbiosis (altered
microbiota) with the depletion of some and enrichment of other bacteria. However,
the significance of gut bacteria that show lower or higher abundance in MS is
unclear. The majority of gut bacteria are associated with certain metabolic
pathways, which in turn help in the maintenance of immune homeostasis of the
host. Here we discuss recent MS microbiome studies and the possible mechanisms
through which gut microbiome might contribute to the pathogenesis of MS.
PMID- 28696138
TI - ADIPOQ/adiponectin induces cytotoxic autophagy in breast cancer cells through
STK11/LKB1-mediated activation of the AMPK-ULK1 axis.
AB - ADIPOQ/adiponectin, an adipocytokine secreted by adipocytes in the breast tumor
microenvironment, negatively regulates cancer cell growth hence increased levels
of ADIPOQ/adiponectin are associated with decreased breast cancer growth.
However, its mechanisms of action remain largely elusive. We report that
ADIPOQ/adiponectin induces a robust accumulation of autophagosomes, increases
MAP1LC3B-II/LC3B-II and decreases SQSTM1/p62 in breast cancer cells.
ADIPOQ/adiponectin-treated cells and xenografts exhibit increased expression of
autophagy-related proteins. LysoTracker Red-staining and tandem-mCherry-GFP-LC3B
assay show that fusion of autophagosomes and lysosomes is augmented upon
ADIPOQ/adiponectin treatment. ADIPOQ/adiponectin significantly inhibits breast
cancer growth and induces apoptosis both in vitro and in vivo, and these events
are preceded by macroautophagy/autophagy, which is integral for
ADIPOQ/adiponectin-mediated cell death. Accordingly, blunting autophagosome
formation, blocking autophagosome-lysosome fusion or genetic-knockout of
BECN1/Beclin1 and ATG7 effectively impedes ADIPOQ/adiponectin induced growth
inhibition and apoptosis-induction. Mechanistic studies show that
ADIPOQ/adiponectin reduces intracellular ATP levels and increases PRKAA1
phosphorylation leading to ULK1 activation. AMPK-inhibition abrogates
ADIPOQ/adiponectin-induced ULK1-activation, LC3B-turnover and SQSTM1/p62
degradation while AMPK-activation potentiates ADIPOQ/adiponectin's effects.
Further, ADIPOQ/adiponectin-mediated AMPK-activation and autophagy-induction are
regulated by upstream master-kinase STK11/LKB1, which is a key node in antitumor
function of ADIPOQ/adiponectin as STK11/LKB1-knockout abrogates
ADIPOQ/adiponectin-mediated inhibition of breast tumorigenesis and molecular
analyses of tumors corroborate in vitro mechanistic findings. ADIPOQ/adiponectin
increases the efficacy of chemotherapeutic agents. Notably, high expression of
ADIPOQ receptor ADIPOR2, ADIPOQ/adiponectin and BECN1 significantly correlates
with increased overall survival in chemotherapy-treated breast cancer patients.
Collectively, these data uncover that ADIPOQ/adiponectin induces autophagic cell
death in breast cancer and provide in vitro and in vivo evidence for the integral
role of STK11/LKB1-AMPK-ULK1 axis in ADIPOQ/adiponectin-mediated cytotoxic
autophagy.
PMID- 28696140
TI - Regulatory roles of 24-epibrassinolide in tolerance of Acacia gerrardii Benth to
salt stress.
AB - This experiment aimed to investigate the role of 24-epibrassinolide (EBL) against
NaCl-induced salinity stress in Acacia gerrardii Benth. NaCl (200 mM) imparted
deleterious effects on the growth and chlorophyll contents of A. gerrardii, but
foliar application of EBL (1.0 mg/l; each plant received 2.5 ml) mitigated the
negative effect considerably. NaCl reduced chlorophyll content but this was
significantly ameliorated by the application of EBL. EBL reduced significantly
NaCl-induced oxidative stress hence protect membranes and also improved the
relative water content significantly by 6.6% as compared with control. Nitrate
reductase activity declined after NaCl treatment but EBL application sustained
its activity under normal and stressed conditions. Exogenous application of EBL
significantly improved the activity of superoxide dismutase, catalase and the
enzymes of the ascorbate-glutathione pathway thereby protecting the
photosynthetic electron transport chain and other metabolic processes in A.
gerrardii from NaCl-induced oxidative stress.
PMID- 28696142
TI - Patent highlights February-March 2017.
PMID- 28696141
TI - Air pollution levels and cardiovascular health: Low is not enough.
PMID- 28696144
TI - The Digest.
PMID- 28696145
TI - Prevention of cardiovascular disease in the working population at high
cardiovascular risk.
PMID- 28696146
TI - Heat Resistance of Histidine Decarboxylase from Gram-Negative Histamine-Producing
Bacteria in Seafood.
AB - Precooking of tuna is a potential critical control point (CCP) in the commercial
manufacturing of canned tuna. To assess the efficacy of precooking as a CCP, an
understanding of the thermal properties of histamine-producing bacteria (HPB) and
their histidine decarboxylase (HDC) enzymes is required. The thermal properties
of many HPB have been determined, but the thermal resistances of the HDC enzymes
are unknown. The purpose of this study was to determine the D- and z-values of
selected HDC enzymes to evaluate the CCP of precooking during the canning process
and provide scientific data to support U.S. Food and Drug Administration
guidelines. HDC (hdc) genes from three strains each of Morganella morganii,
Enterobacter aerogenes, Raoultella planticola, and Photobacterium damselae were
cloned, expressed, and purified using the Champion pET Directional TOPO
Expression System, pET100 cloning vector, and HisPur Cobalt resin. The heat
resistances of all enzymes were compared at 50 degrees C, and the D- and z-values
from one strain of each HPB were determined at 50 to 60 degrees C. To evaluate
the heat inactivation of HDC enzymes during canned tuna processing, tuna tissue
was inoculated with HDCs and heated to 60 degrees C in a water bath set at 65 and
100 degrees C. The D-values for the HDC enzymes from M. morganii, E. aerogenes,
R. planticola, and P. damselae ranged from 1.6 to 4.1, 1.6 to 6.3, 1.9 to 4.3,
and 1.6 to 2.9 min, respectively, at 50 to 60 degrees C. The z-values for M.
morganii, E. aerogenes, R. planticola, and P. damselae were 19.2, 18.0, 22.0, and
13.3 degrees C, respectively. The HDCs from all HPB except E. aerogenes showed no
significant activity after being heated to 60 degrees C. The data generated in
this study will help refine current guidelines for the thermal destruction of the
HDC enzymes.
PMID- 28696147
TI - Effects of Desiccation Practices of Cultured Atlantic Oysters (Crassostrea
virginica) on Vibrio spp. in Portersville Bay, Alabama, USA.
AB - The expansion of off-bottom aquaculture to the Gulf of Mexico has raised public
health concerns for human health officials. High temperatures in the Gulf of
Mexico are associated with high levels of Vibrio parahaemolyticus and Vibrio
vulnificus. Routine desiccation practices associated with off-bottom aquaculture
expose oysters to ambient air, allowing Vibrio spp. to proliferate in the closed
oyster. Currently, there is limited research on the length of time needed for
Vibrio spp. levels in desiccated oysters to return to background levels, defined
as the levels found in oysters that remain continually submersed and not exposed
to ambient air. This study determined the time needed to return V.
parahaemolyticus, V. vulnificus, and Vibrio cholerae levels to background levels
in oysters exposed to the following desiccation practices: 3-h freshwater dip
followed by 24-h ambient air exposure, 27-h ambient air exposure, and control.
All oysters were submerged at least 2 weeks prior to the beginning of each trial,
with the control samples remaining submerged for the duration of each trial.
Vibrio spp. levels were enumerated from samples collected on days 0, 1, 2, 3, 7,
10, and 14 after resubmersion using a three-tube most-probable-number enrichment
followed by BAX PCR. V. cholerae levels were frequently (92%) below the limit of
detection at all times, so they were not statistically analyzed. V.
parahaemolyticus and V. vulnificus levels in the 27-h ambient air exposure and
the 3-h freshwater dip followed by 24-h ambient air exposure samples were
significantly elevated compared with background samples. In most cases, the
Vibrio spp. levels in oysters in both desiccation treatments remained elevated
compared with background levels until 2 or 3 days post-resubmersion. However,
there was one trial in which the Vibrio spp. levels did not return to background
levels until day 7. The results of this study provide scientific support that
oyster farmers should be required to implement a minimum 7-day resubmersion
regimen. This length of time allowed the Vibrio spp. levels to become not
significantly different across all treatments.
PMID- 28696148
TI - 3D printing of pharmaceuticals: patent and regulatory challenges.
PMID- 28696149
TI - Immune checkpoint inhibitors: the battle of giants.
PMID- 28696150
TI - Curative-intent radical en bloc resection using a minimum of a 3 cm margin in
feline injection-site sarcomas: a retrospective analysis of 131 cases.
AB - Objectives Owing to its highly infiltrative growth, feline injection-site sarcoma
(FISS) carries a significant risk of local tumour recurrence. Parameters of
possible prognostic significance (eg, tumour size and location, resection of de
novo vs recurrent tumours, and achievement of tumour-free surgical margins) were
examined with regard to their influence on recurrence rate (RR), disease-free
interval (DFI) and survival time (ST). Methods This was a retrospective analysis
of cats with FISSs located on the chest or abdominal wall or the interscapular
region treated in a single institution using a standardised radical resection
technique with 3 cm lateral margins and full-thickness body wall resection
(tumours over chest/abdominal wall) or a minimum of two fascial planes
(interscapular tumours). Results Median postoperative DFI and ST of 131 cats with
FISSs was 21 and 24 months, respectively. Patients operated on for recurrent
tumours were significantly more likely to die from tumour-related reasons
compared with patients with de novo tumours ( P <0.001). RR and DFI in the
different tumour locations were comparable ( P = 0.544 and P = 0.17,
respectively). Local tumour recurrence occurred in 38.1% of the cats. Cats
operated on for tumour recurrences had a significantly higher chance of another
recurrence (RR 55.5% vs 33.3%; P = 0.005). Completeness of excision was
determined by taking tumour bed biopsies. Tumour bed biopsies that did not
contain tumour cells were associated with a significantly lower RR compared with
those with tumour cells (30.5% vs 76.2%). Conclusions and relevance Depending on
prognostic factors such as surgery for primary vs recurrent tumour, tumour-free
resection margins and tumour location, the RR in FISS ranges from 33-55%, despite
curative intent radical surgery. This study may help in identifying patients at
risk for recurrence.
PMID- 28696151
TI - Paravertebral brachial plexus blockade in cats: a cadaver study.
AB - Objectives The aims of this study were to describe the paravertebral brachial
plexus (PBP) blockade in cats, and compare the spread of bupivacaine-methylene
blue solution (BMS) using two volumes of injection into the PBP. Methods Six
cadavers (4.4 +/- 1.8 kg) randomly received 0.15 ml/kg (LOW) or 0.2 ml/kg (HIGH)
per injection of BMS into the PBP. The first injection was made ventral to the
transverse process of the sixth cervical vertebra (nerves C6 and C7) at the
emergence of nerve roots. A second injection was performed at the edge of the
cranial border of the scapula and directed ventrally towards the first rib (C8
and T1). Cadavers were dissected and the presence of BMS in contact with the
nerves (success rate) and length of staining were evaluated for each nerve
(C6/C7/C8/T1). Length of target nerves in contact with BMS was measured and <15
mm was considered fair, ?15 mm sufficient and >40 mm excessive. Complications
(aspiration of blood, staining of pleural space and/or spinal cord) were
recorded. Paired t-test, Mann-Whitney U-test and chi2 test were used for
statistical analysis when appropriate ( P <0.05). Results Eleven hemilateral
brachial plexuses were injected. Aspiration of blood occurred during one
injection. Inadvertent pleural or spinal staining was not observed. Success rates
(positive nerve staining) in the LOW and HIGH groups, respectively, were as
follows: C6: 83% and 80%; C7: 66% and 100%; C8: 66% and 100%; T1: 50% and 60% ( P
>0.05). Median (range) length of nerve staining was 22 mm (15-39 mm) for LOW and
21 mm (13-35 mm) for HIGH ( P >0.05). Excessive nerve staining was not recorded.
Conclusions and relevance This study describes the PBP blockade in cats with
acceptable nerve staining and minimal complications. Success rate and length of
nerve staining were not significantly different between the LOW and HIGH groups.
PMID- 28696152
TI - The effectiveness of exercise-based telemedicine on pain, physical activity and
quality of life in the treatment of chronic pain: A systematic review.
AB - Introduction The aim of this study was to systematically review the evidence on
the effectiveness of exercise-based telemedicine in chronic pain. Methods We
searched the Cochrane, PubMed, MEDLINE, EMBASE, CINAHL and PEDRO databases from
2000 to 2015 for randomised controlled trials, comparing exercise-based
telemedicine intervention to no intervention or usual care in adults with chronic
pain. Primary outcome data were pooled using random effect meta-analysis. Primary
outcomes were pain, physical activity (PA), limitations in activities of daily
living (ADL) and quality of life (QoL). Secondary outcomes were barriers,
facilitators and usability of telemedicine. Results Sixteen studies were
included. Meta-analyses were performed in three subgroups of studies with
comparable control conditions. Telemedicine versus no intervention showed
significantly lower pain scores (MD -0.57, 95% CI -0.81; -0.34), but not for
telemedicine versus usual care (MD -0.08, 95% CI -0.41; 0.26) or in addition to
usual care (MD -0.25, 95% CI -1.50; 1.00). Telemedicine compared to no
intervention showed non-significant effects for PA (MD 19.93 min/week, 95% CI
5.20; 45.06) and significantly diminished ADL limitations (SMD -0.20, 95% CI
0.29; -0.12). No differences were found for telemedicine in addition to usual
care for PA or for ADL (SMD 0.16, 95% CI -0.66; 0.34). Telemedicine versus usual
care showed no differences for ADL (SMD 0.08, 95% CI -0.37; 0.53). No differences
were found for telemedicine compared to the three control groups for QoL. Limited
information was found on the secondary outcomes. Conclusions Exercise-based
telemedicine interventions do not seem to have added value to usual care. As
substitution of usual care, telemedicine might be applicable but due to limited
quality of the evidence, further exploration is needed for the rapidly developing
field of telemedicine.
PMID- 28696153
TI - Efficacy of cognitive behavioural therapy delivered over the Internet for
depressive symptoms: A systematic review and meta-analysis.
AB - Introduction Cognitive behavioural therapy has been shown to improve depressive
symptoms in adults with mild to moderate depression. To overcome many of the
barriers associated with delivering this treatment, attempts have been made to
deliver cognitive behavioural therapy via the Internet. The objective of this
meta-analysis is to assess whether Internet-based cognitive behavioural therapy
delivered to adults with depressive symptoms leads to a reduction in these
symptoms as compared to those who receive no therapy. Methods In September 2015,
the Cochrane, PubMed and PsycInfo databases were searched; studies were also
found through bibliography searches. Studies were included if they were
randomized controlled trials published in English between 2005-2015 conducted
with adults >18 years of age experiencing mild to moderate depression where study
subjects received Internet-based cognitive behavioural therapy, and the control
group was placed on a wait-list. The search yielded 257 articles; 14 of these
were included in the meta-analysis. Results Internet delivered cognitive
behavioural therapy had a medium effect on reducing depressive symptoms at the
end of the study period (standardized mean difference: 0.74, confidence interval:
0.62-0.86, p < 0.001). Internet-delivered cognitive behavioural therapy also has
a large sustained effect in maintaining reduction of depressive symptoms in
follow-up measures done 3-6 months after the conclusion of the therapy
(standardized mean difference: 0.83, confidence interval: 0.69-0.99, p < 0.001).
There was no publication bias and low heterogeneity. Discussion Cognitive
behavioural therapy delivered over the Internet leads to immediate and sustained
reduction in depressive symptoms; thus, it may be a good treatment modality for
individuals unable or unwilling to access traditional face-to-face therapy.
PMID- 28696154
TI - Extrahepatic manifestations of HCV: the role of direct acting antivirals.
AB - INTRODUCTION: Hepatitis C virus (HCV) represents a major health concern, as
nearly 3 million people become newly infected by this pathogen annually. The
majority of infected individuals fail to clear the virus, and chronicity is
established. Chronic HCV patients are at high risk for liver disease, ranging
from mild fibrosis to cirrhosis and severe hepatocellular carcinoma. Over the
last few years, the development of multiple direct acting antivirals (DAA) have
revolutionized the HCV infection treatment, demonstrating cure rates higher than
90%, and showing less side effects than previous interferon-based regimens. Areas
covered: Besides liver, HCV infection affects a variety of organs, therefore
inducing diverse extrahepatic manifestations. This review covers clinical,
experimental, and epidemiological publications regarding systemic manifestations
of HCV, as well as recent studies focused on the effect of DAA in such
conditions. Expert commentary: Though further research is needed; available data
suggest that HCV eradication is often associated with the improvement of
extrahepatic symptoms. Therefore, the emergence of DAA would offer the
opportunity to treat both HCV infection and its systemic manifestations,
requiring shorter treatment duration and driving minor adverse effects.
PMID- 28696155
TI - Studies of the precipitation pattern of paclitaxel in intravenous infusions and
rat plasma using laser nephelometry.
AB - Cremophor EL (CrEL) is commonly used to solubilize paclitaxel (Ptx); a widely
established anticancer agent used against many types of cancer. Using laser-based
microplate nephelometry, in this work we assessed the precipitation kinetics of
Ptx in CrEL-containing formulations upon dilutions with different infusion media
or upon introduction into rat plasma. The precipitation profile of Ptx was
assessed for a Taxol-like formulation and compared with a preparation with
reduced CrEL content. These two formulations were diluted at various ratios in
compatible infusion media and with or without rat plasma. The percentages of Ptx
precipitated in dilution media and protein-binding in plasma were quantified
using HPLC. The findings of turbidity measurements were in good agreement with
HPLC. Despite the presence of albumin, it was possible to assess turbidity within
infusion solutions and predict Ptx precipitation. Upon addition to plasma, no
precipitation in Taxol-like formulation occurred after 2 h. In contrast,
precipitation occurred immediately in CrEL-reduced formulation. It is possible
that the high percentage of protein-bound Ptx in plasma (98.5-99.2%) has
inhibited drug precipitation. Turbidity measurements using laser nephelometry can
provide a rapid screening tool when developing intravenous formulations for
poorly soluble drugs, such as Ptx and assess its stability upon dilution in
animal plasma.
PMID- 28696156
TI - The IGF-1R/AKT pathway has opposing effects on Nutlin-3a-induced apoptosis.
AB - Nutlin-3a is a small molecule MDM2 antagonist and potent activator of wild-type
p53. Nutlin-3a disrupts MDM2 binding to p53, thus increasing p53 levels and
allowing p53 to inhibit proliferation or induce cell death. Factors that control
sensitivity to Nutlin-3a-induced apoptosis are incompletely understood. In this
study we isolated cisplatin-resistant clones from MHM cells, an MDM2-amplified
and p53 wild-type osteosarcoma cell line. Cisplatin resistance in these clones
resulted in part from heightened activation of the IGF-1R/AKT pathway.
Interestingly, these cisplatin resistant clones showed hyper-sensitivity to
Nutlin-3a induced apoptosis. Increased Nutlin-3a sensitivity was associated with
reduced authophagy flux and a greater increase in p53 levels in response to
Nutlin-3a treatment. IGF-1R and AKT inhibitors further increased apoptosis by
Nutlin-3a in parental MHM cells and the cisplatin-resistant clones, confirming
IGF-1R/AKT signaling promotes apoptosis resistance. However, IGF-1R and AKT
inhibitors also reduced p53 accumulation in Nutlin-3a treated cells and increased
autophagy flux, which we showed can promote apoptosis resistance. We conclude the
IGF-1R/AKT pathway has opposing effects on Nutlin-3a-induced apoptosis. First, it
can inhibit apoptosis, consistent with its well-established role as a survival
signaling pathway. Second, it can enhance Nutlin-3a induced apoptosis through a
combination of maintaining p53 levels and inhibiting pro-survival autophagy.
PMID- 28696157
TI - Toward carbon monoxide based therapeutics: carbon monoxide in a pill.
AB - As one of the three known gasotransmitters, carbon monoxide (CO) has demonstrated
therapeutic potential against a wide range of human diseases. However,
development of CO as a therapeutic agent is severely impeded, primarily due to
the lack of pharmaceutically acceptable delivery forms of CO. Gaseous CO may only
have limited utility under carefully controlled clinical environment. As a
result, there have been efforts in developing metal-based CO-releasing molecules
and organic CO-releasing molecules that require light activation. We are
interested in developing CO prodrugs, which are metal free and release CO
spontaneously under physiological conditions without light irradiation. In this
review, we summarize progress in this area with a focus on a recent patent and
related publications.
PMID- 28696158
TI - Immunization with HIV-1 envelope T20-encoding DNA vaccines elicits cross-clade
neutralizing antibody responses.
AB - BACKGROUND: Genetic immunization is expected to induce the expression of antigens
in a native form. The encoded peptide epitopes are presented on endogenous MHC
molecules, mimicking antigen presentation during a viral infection. We have
explored the potential of enfuvirtide (T20), a short HIV peptide with antiviral
properties, to enhance immune response to HIV antigens. To generate an expression
vector, the T20 sequence was cloned into a conventional plasmid, the novel
minicircle construct, and a replicon plasmid. In addition, 3 conventional
plasmids that express the envelope of HIV-1 subtypes A, B and C and contain T20
in their gp41 sequences were also tested. RESULTS: All combinations induced HIV
specific antibodies and cellular responses. The addition of T20 as a peptide and
as an expression cassette in the 3 DNA vectors enhanced antibody responses. The
highest anti-HIV-1 Env titers were obtained by the replicon T20 construct. This
demonstrates that besides its known antiviral activity, T20 promotes immune
responses. We also confirm that the combination of slightly divergent antigens
improves immune responses. CONCLUSIONS: The antiretroviral T20 HIV-1 sequence can
be used as an immunogen to elicit binding and neutralizing antibodies against HIV
1. These, or similarly modified gp41 genes/peptides, can be used as priming or
boosting components for induction of broadly neutralizing anti-HIV antibodies.
Future comparative studies will reveal the optimal mode of T20 administration.
PMID- 28696159
TI - Quality of reporting of otorhinolaryngology articles using animal models with the
ARRIVE statement.
AB - Research involving animal models is crucial for the advancement of science,
provided that experiments are designed, performed, interpreted, and reported
well. In order to investigate the quality of reporting of articles in
otorhinolaryngology research using animal models, a PubMed database search was
conducted to retrieve eligible articles. The checklist of the ARRIVE (Animal
Research: Reporting of In Vivo Experiments) guidelines was used to assess the
quality of reporting of articles published in ear, nose and throat (ENT) and
multidisciplinary journals. Two authors screened titles, abstracts, and full
texts to select articles reporting otorhinolaryngology research using in vivo
animal models. ENT journals ( n = 35) reported a mean of 57.1% adequately scored
ARRIVE items (median: 58.3%; 95% confidence interval [CI; 53.4-60.9%]), while
articles published in multidisciplinary journals ( n = 36) reported a mean of
49.1% adequately scored items (median: 50.0; 95% CI [46.2-52.0%]). Articles
published in ENT journals showed better quality of reporting of animal studies
based on the ARRIVE guidelines ( P < 0.05). However, adherence to the ARRIVE
guidelines is generally poor in otorhinolaryngology research using in vivo animal
models. The endorsement of the ARRIVE guidelines by authors, research and
academic institutes, editorial offices and funding agencies is recommended for
improved reporting of scientific research using animal models.
PMID- 28696160
TI - Guidelines on severity assessment and classification of genetically altered mouse
and rat lines.
AB - Genetic alterations can unpredictably compromise the wellbeing of animals. Thus,
more or less harmful phenotypes might appear in the animals used in research
projects even when they are not subjected to experimental treatments. The
severity classification of suffering has become an important issue since the
implementation of Directive 2010/63/EU on the protection of animals used for
scientific purposes. Accordingly, the breeding and maintenance of genetically
altered (GA) animals which are likely to develop a harmful phenotype has to be
authorized. However, a determination of the degree of severity is rather
challenging due to the large variety of phenotypes. Here, the Working Group of
Berlin Animal Welfare Officers (WG Berlin AWO) provides field-tested guidelines
on severity assessment and classification of GA rodents. With a focus on basic
welfare assessment and severity classification we provide a list of symptoms that
have been classified as non-harmful, mild, moderate or severe burdens.
Corresponding monitoring and refinement strategies as well as specific housing
requirements have been compiled and are strongly recommended to improve hitherto
applied breeding procedures and conditions. The document serves as a guide to
determine the degree of severity for an observed phenotype. The aim is to support
scientists, animal care takers, animal welfare bodies and competent authorities
with this task, and thereby make an important contribution to a European
harmonization of severity assessments for the continually increasing number of GA
rodents.
PMID- 28696161
TI - Comparison of normal facial nerve enhancement at 3T MRI using gadobutrol and
gadopentetate dimeglumine.
AB - Background and purpose The facial nerve is unique among cranial nerves in
demonstrating normal enhancement of particular segments. The effect of varying T1
relaxivities of gadolinium-based contrast agents on facial nerve enhancement is
unclear. In this study, we assess differences in normal facial nerve enhancement
with two different gadolinium-based contrast agents, gadobutrol and gadopentetate
dimeglumine. In addition, we evaluate differences in facial nerve enhancement
with spin-echo (SE) T1 versus 3D inversion recovery prepared fast spoiled
gradient-echo (FSPGR) post-contrast sequences. Methods A total of 140 facial
nerves in 70 individuals were evaluated (70 with gadobutrol and 70 with
gadopentetate dimeglumine) by two blinded reviewers. Differences in enhancement
of facial nerve segments between the two agents were analyzed. Differences in
enhancement between SE T1 and FSPGR imaging were also evaluated. Results There
was no significant difference in facial nerve enhancement between gadobutrol and
gadopentetate dimeglumine. Enhancement was commonly observed in the geniculate,
tympanic and mastoid segments (98%-100%) with either contrast agent; enhancement
was less common in the labyrinthine segments (9%-14%) and lateral canalicular
segment (2%-5%). There was a smaller enhancing proportion of labyrinthine and
tympanic segments with FSPGR as compared to SE T1 images with gadobutrol.
Conclusion There is no significant difference in overall enhancement of the
facial nerve between gadobutrol and gadopentetate dimeglumine. Mild enhancement
of the lateral canalicular portion of the facial nerve may be a normal finding.
With FSPGR sequence, there is lesser perceived enhancement of the labyrinthine
and tympanic segments of the facial nerve with gadobutrol.
PMID- 28696162
TI - Physiological and brain alterations produced by high-fat diet in male and female
rats can be modulated by increased levels of estradiol during critical periods of
development.
AB - BACKGROUND: Overnutrition due to a high-fat diet (HFD) can increase the
vulnerability of the metabolic system to maladjustments. Estradiol has an
inhibitory role on food intake and this hormone has demonstrated to be a crucial
organizer during brain development. OBJECTIVE: Our aim was to determine whether
increased levels of estradiol in the early postnatal period modulate the
alterations in metabolism and brain metabolic circuits produced by overnutrition.
METHODS: Twenty-four male and 24 female Wistar rats were submitted to a HFD
(34.9% fat) or a control diet (5% fat) from gestational day 6. From postnatal (P)
6 to P13, both control and HFD groups were administered a s.c. injection of
vehicle or estradiol benzoate (0.4 mg/kg), resulting in eight experimental groups
(n = 6 in each group). Body weight, food intake and subcutaneous, visceral, and
brown fat pads were measured. Agouti-related peptide, neuropeptide Y, orexin, and
proopiomelanocortin (POMC) were analyzed by quantitative real-time polymerase
chain reaction assay and plasma estradiol levels were measured by ELISA. RESULTS:
Males fed a HFD showed an increase in body weight and the amount of visceral and
subcutaneous fat, which was coincident with an increase in the number of
kilocalories ingested. Neonatal estradiol treatment restored the body weight and
subcutaneous fat of HFD males to control levels. Hypothalamic POMC mRNA levels in
HFD females were increased with respect to control females. This increase was
reverted with estradiol treatment during development. DISCUSSION: HFD and
estradiol treatment have different effects on males and females. Overnutrition
affects physiological parameters, such as body weight, visceral, and subcutaneous
fat content, in males, while females present alterations in hypothalamic POMC
mRNA levels. Hence, the increase in estradiol levels during a period that is
critical for the programing of the feeding system can modulate some of the
alterations produced by the continuous intake of high-fat content food.
PMID- 28696163
TI - Evaluation of dietary and lifestyle changes as modifiers of S100beta levels in
Alzheimer's disease.
AB - There is a significant body of research undertaken in order to elucidate the
mechanisms underlying the pathology of Alzheimer's disease (AD), as well as to
discover early detection biomarkers and potential therapeutic strategies. One
such proposed biomarker is the calcium binding protein S100beta, which, depending
on its local concentration, is known to exhibit both neurotrophic and
neuroinflammatory properties in the central nervous system. At present,
relatively little is known regarding the effect of chronic S100beta disruption in
AD. Dietary intake has been identified as a modifiable risk factor for AD.
Preliminary in vitro and animal studies have demonstrated an association between
S100beta expression and dietary intake which links to AD pathophysiology. This
review describes the association of S100beta to fatty acids, ketone bodies,
insulin, and botanicals as well as the potential impact of physical activity as a
lifestyle factor. We also discuss the prospective implications of these findings,
including support of the use of a Mediterranean dietary pattern and/or the
ketogenic diet as an approach to modify AD risk.
PMID- 28696165
TI - Quantifying the performance of a hybrid anion exchanger/adsorbent for phosphorus
removal using mass spectrometry coupled with batch kinetic trials.
AB - Increasingly stricter phosphorus discharge limits represent a significant
challenge for the wastewater industry. Hybrid media comprising anionic exchange
resins with dispersions of hydrated ferric oxide nanoparticles have been shown to
selectively remove phosphorus from wastewaters, and display greater capacity and
operational capability than both conventional treatment techniques and other
ferric-based adsorbent materials. Spectrographic analyses of the internal
surfaces of a hybrid media during kinetic experiments show that the adsorption of
phosphorus is very rapid, utilising 54% of the total capacity of the media within
the first 15 min and 95% within the first 60 min. These analyses demonstrate the
importance of intraparticle diffusion on the overall rate in relation to the
penetration of phosphorus. Operational capacity is a function of the target
effluent phosphorus concentration and for 0.1 mg P L-1, this is [Formula: see
text], which is 8-13% of the exhaustive capacity. The adsorbed phosphorus can be
selectively recovered, offering a potential route to recycle this important
nutrient. The main implication of the work is that the ferric nanoparticle
adsorbent can provide a highly effective means of achieving a final effluent
phosphorus concentration of 0.1 mg P L-1, even when treating sewage effluent at 5
mg P L-1.
PMID- 28696166
TI - CellzDirect gives new hope for patent protection for personalized medicine in the
USA.
PMID- 28696164
TI - Surgical Predictors of Clinical Outcomes After Revision Anterior Cruciate
Ligament Reconstruction.
AB - BACKGROUND: Revision anterior cruciate ligament (ACL) reconstruction has been
documented to have worse outcomes compared with primary ACL reconstruction.
HYPOTHESIS: Certain factors under the control of the surgeon at the time of
revision surgery can both negatively and positively affect outcomes. STUDY
DESIGN: Case-control study; Level of evidence, 3. METHODS: Patients undergoing
revision ACL reconstruction were identified and prospectively enrolled between
2006 and 2011. Data collected included baseline demographics, intraoperative
surgical technique and joint disorders, and a series of validated patient
reported outcome instruments (International Knee Documentation Committee [IKDC]
subjective form, Knee Injury and Osteoarthritis Outcome Score [KOOS], Western
Ontario and McMaster Universities Osteoarthritis Index [WOMAC], and Marx activity
rating scale) completed before surgery. Patients were followed up for 2 years and
asked to complete an identical set of outcome instruments. Regression analysis
was used to control for age, sex, body mass index (BMI), activity level, baseline
outcome scores, revision number, time since last ACL reconstruction, and a
variety of previous and current surgical variables to assess the surgical risk
factors for clinical outcomes 2 years after revision ACL reconstruction. RESULTS:
A total of 1205 patients (697 male [58%]) met the inclusion criteria and were
successfully enrolled. The median age was 26 years, and the median time since
their last ACL reconstruction was 3.4 years. Two-year follow-up was obtained on
82% (989/1205). Both previous and current surgical factors were found to be
significant contributors toward poorer clinical outcomes at 2 years. Having
undergone previous arthrotomy (nonarthroscopic open approach) for ACL
reconstruction compared with the 1-incision technique resulted in significantly
poorer outcomes for the 2-year IKDC ( P = .037; odds ratio [OR], 2.43; 95% CI,
1.05-5.88) and KOOS pain, sports/recreation, and quality of life (QOL) subscales
( P <= .05; OR range, 2.38-4.35; 95% CI, 1.03-10.00). The use of a metal
interference screw for current femoral fixation resulted in significantly better
outcomes for the 2-year KOOS symptoms, pain, and QOL subscales ( P <= .05; OR
range, 1.70-1.96; 95% CI, 1.00-3.33) as well as WOMAC stiffness subscale ( P =
.041; OR, 1.75; 95% CI, 1.02-3.03). Not performing notchplasty at revision
significantly improved 2-year outcomes for the IKDC ( P = .013; OR, 1.47; 95% CI,
1.08-1.99), KOOS activities of daily living (ADL) and QOL subscales ( P <= .04;
OR range, 1.40-1.41; 95% CI, 1.03-1.93), and WOMAC stiffness and ADL subscales (
P <= .04; OR range, 1.41-1.49; 95% CI, 1.03-2.05). Factors before revision ACL
reconstruction that increased the risk of poorer clinical outcomes at 2 years
included lower baseline outcome scores, a lower Marx activity score at the time
of revision, a higher BMI, female sex, and a shorter time since the patient's
last ACL reconstruction. Prior femoral fixation, prior femoral tunnel aperture
position, and knee flexion angle at the time of revision graft fixation were not
found to affect 2-year outcomes in this revision cohort. CONCLUSION: There are
certain surgical variables that the physician can control at the time of revision
ACL reconstruction that can modify clinical outcomes at 2 years. Whenever
possible, opting for an anteromedial portal or transtibial surgical exposure,
choosing a metal interference screw for femoral fixation, and not performing
notchplasty are associated with significantly better 2-year clinical outcomes.
PMID- 28696167
TI - Neuroprotective effect of alpha-mangostin on mitochondrial dysfunction and alpha
synuclein aggregation in rotenone-induced model of Parkinson's disease in
differentiated SH-SY5Y cells.
AB - The study was designed to evaluate the protective effect of alpha-mangostin and
explore its mechanism in an in vitro model of Parkinson's disease (PD) induced by
rotenone. SH-SY5Y cells were treated with rotenone and alpha-mangostin for 24 h.
alpha-Mangostin significantly and concentration-dependently inhibited rotenone
induced cytotoxicity. The rotenone-induced aggregation of alpha-synuclein and
loss of TH were alleviated by alpha-mangostin. alpha-Mangostin treatment also
reversed the rotenone-induced overproduction of reactive oxygen species,
activation of caspases (-8 and -3) and mitochondrial dysfunction, reflected by
decrease in mitochondrial membrane potential and cellular ATP levels. These
findings suggest that alpha-mangostin has neuroprotective effects against PD
related neuronal injury.
PMID- 28696168
TI - Point of no return for improvement of cartilage quality indicated by dGEMRIC
before and after weight loss in patients with knee osteoarthritis: a cohort
study.
AB - Background It has been demonstrated that weight loss improves symptoms in obese
subjects with knee osteoarthritis (KOA). A parallel change in cartilage
morphology remains to be demonstrated. Purpose To demonstrate a parallel change
in cartilage morphology. Material and Methods Obese patients with KOA were
examined before and after weight loss over 16 weeks. Target knee joints were
radiographically assessed by the Kellgren/Lawrence grading (KLG) system. Patients
with KLG-1 and 2 changes in the lateral compartment were included. Delayed
gadolinium-enhanced MRI of cartilage (dGEMRIC) was performed using intra
articular contrast. Results Nine patients with lateral KLG-1 and ten patients
with lateral KLG-2 were studied. There were no group differences regarding the
lateral compartment baseline dGEMRIC T1 values: median = 497 ms (KLG-1) and 533
ms (KLG-2) ( P = 0.12), or regarding reduction in body mass index (BMI) after 16
weeks: 12.8% versus 11.4% ( P = 0.74). In the KLG-1 group, several cases of
increased dGEMRIC T1 values were seen and median value decreased significantly
less than in KLG-2 group (15 ms versus 41 ms, P = 0.03) after weight loss.
Conclusion Improvement of cartilage quality, assessed with dGEMRIC, after weight
loss might be possible in early stage KOA (KLG-1), but not in later stage KOA
(KLG-2). The results may suggest a point of no return for improvement of
cartilage quality that should be tested in larger trials.
PMID- 28696169
TI - Can the apparent diffusion coefficient differentiate the grade of endometrioid
adenocarcinoma and the histological subtype of endometrial cancer?
AB - Background Diffusion-weighted imaging (DWI) provides useful information for the
identification of benign and malignant uterine lesions. However, the use of the
apparent diffusion coefficient (ADC) for histopathological grading of endometrial
cancer is controversial. Purpose To explore the use of ADC values in
differentiating the preoperative tumor grading of endometrioid adenocarcinomas
and investigate the relationship between the ADC values of endometrial cancer and
the histological tumor subtype. Material and Methods We retrospectively evaluated
98 patients with endometrial cancers, including both endometrioid adenocarcinomas
(n = 80) and non-endometrioid adenocarcinomas (n = 18). All patients underwent
DWI procedures and ADC values were calculated. The Kruskal-Wallis test and the
independent samples Mann-Whitney U test were used to compare differences in the
ADC values between different tumor grades and different histological subtypes.
Results The mean ADC values (ADCmean) for high-grade endometrioid adenocarcinomas
were significantly lower than the values for low-grade tumors (0.800 versus 0.962
* 10-3 mm2/s) ( P = 0.002). However, no significant differences in ADCmean and
minimum ADC values (ADCmin) were found between tumor grades (G1, G2, and G3) of
endometrial cancer. Compared with endometrioid adenocarcinomas, the
adenocarcinoma with squamous differentiation showed lower ADC values
(mean/minimum = 0.863/0.636 versus 0.962/0.689 * 10-3 mm2/s), but the differences
were not significant ( Pmean = 0.074, Pmin = 0.441). Moreover, ADCmean for
carcinosarcomas was significantly higher than the value for G3 non-carcinosarcoma
endometrial cancers (1.047 versus 0.823 * 10-3 mm2/s) ( P = 0.001). Conclusion
The ADCmean was useful for identifying high-grade and low-grade endometrioid
adenocarcinomas. Additionally, squamous differentiation may decrease ADCmean and
ADCmin of endometrioid adenocarcinoma, and carcinosarcomas showed relatively high
ADCmean.
PMID- 28696170
TI - Predicting Ascospore Release of Monilinia vaccinii-corymbosi of Blueberry with
Machine Learning.
AB - Mummy berry, caused by Monilinia vaccinii-corymbosi, causes economic losses of
highbush blueberry in the U.S. Pacific Northwest (PNW). Apothecia develop from
mummified berries overwintering on soil surfaces and produce ascospores that
infect tissue emerging from floral and vegetative buds. Disease control currently
relies on fungicides applied on a calendar basis rather than inoculum
availability. To establish a prediction model for ascospore release, apothecial
development was tracked in three fields, one in western Oregon and two in
northwestern Washington in 2015 and 2016. Air and soil temperature,
precipitation, soil moisture, leaf wetness, relative humidity and solar radiation
were monitored using in-field weather stations and Washington State University's
AgWeatherNet stations. Four modeling approaches were compared: logistic
regression, multivariate adaptive regression splines, artificial neural networks,
and random forest. A supervised learning approach was used to train the models on
two data sets: training (70%) and testing (30%). The importance of environmental
factors was calculated for each model separately. Soil temperature, soil
moisture, and solar radiation were identified as the most important factors
influencing ascospore release. Random forest models, with 78% accuracy, showed
the best performance compared with the other models. Results of this research
helps PNW blueberry growers to optimize fungicide use and reduce production
costs.
PMID- 28696171
TI - Multiple Sclerosis-Associated Uveitis.
PMID- 28696172
TI - Multimodal Imaging in Retinal Vasculitis.
AB - Retinal vasculitis presents with inflammation involving the retinal vasculature
as an isolated disease or in combination with other ocular or systemic
conditions. This entity may be associated with a wide variety of clinical
manifestations such as vascular sheathing, cotton-wool spots, retinal ischemia,
and neovascularization. Often, retinal vasculitis and its complications lead to
diagnostic challenges in identifying the exact etiology of the inflammation.
Ancillary investigations such as fundus photography, fluorescein angiography, and
more recently, adaptive optics imaging and optical coherence tomography
angiography, may provide valuable information that help in establishing the exact
diagnosis and initiation of appropriate therapy. In the index review, multimodal
imaging features of retinal vasculitis are described. In addition, detection of
vascular inflammation using novel noncontact imaging techniques has been
highlighted.
PMID- 28696173
TI - Multimodal Imaging in Anterior Uveitis.
AB - Anterior uveitis is the most common group of uveitis worldwide, with a diverse
spectrum ranging from autoimmune and infectious to masquerade etiologies.
Elucidation of the underlying etiology may be challenging, but it remains
important, especially for recurrent uveitis. Multimodal imaging has improved our
understanding and management of many posterior uveitis and panuveitis. Similarly,
a wide variety of anterior segment ophthalmic imaging techniques are available to
allow the monitoring of the structural changes that may develop during anterior
uveitis. These include anterior segment photography, specular microscopy, in vivo
confocal microscopy, anterior segment optical coherence tomography (AS-OCT),
ultrasound biomicroscopy (UBM), laser flare photometry, and less commonly used
techniques such as anterior segment fluorescein and indocyanine green
angiography, iris autofluorescence, and infrared imaging. This review
recapitulates the past and recent application of these ophthalmic imaging
modalities to the diagnosis and management of anterior uveitis.
PMID- 28696174
TI - Bilateral lateral ventricular subependymoma with extensive multiplicity
presenting with hemorrhage.
AB - This 48-year-old-man who had undergone right thyroid lobectomy for
undifferentiated thyroid carcinoma nine years earlier developed generalized
seizures. His cerebrospinal fluid was xanthochromic with elevation of total
protein. Computed tomography (CT) showed mixed-density bilateral ventricular
masses. Magnetic resonance imaging (MRI) revealed multiple nodules in both
lateral ventricles; they were heterogeneously enhanced by gadolinium. Diffuse
hyperintensity in the right medial temporal lobe and bilateral subependymal area
was noted on fluid-attenuated inversion recovery images. Susceptibility-weighted
imaging showed low intensity in the masses and cerebellar sulci suggesting
hemorrhage and hemosiderin deposition. The preoperative diagnosis was
disseminated malignant tumor with recurring hemorrhage. Histological examination
of biopsy specimens showed clusters of cells with small uniform nuclei embedded
in a dense fibrillary matrix of glial cells and microcystic degeneration. Pseudo
rosettes indicating ependymoma were absent. Microhemorrhages and hemosiderin
deposits were noted. Immunohistochemically, the background fibrillary matrix and
neoplastic cells were positive for glial fibrillary acidic protein. Mutated
isocitrate dehydrogenase-1 was negative. The MIB-1 index was 1.5%. The tumor was
pathologically diagnosed as subependymoma containing microhemorrhages and
hemosiderin deposits. The extensive multiplicity and hemorrhage encountered in
this case have rarely been reported in patients with subependymoma.
PMID- 28696175
TI - Venetoclax: A novel B-cell lymphoma-2 inhibitor for chronic lymphocytic leukemia
and other hematologic malignancies.
AB - Patients with chronic lymphocytic leukemia with the 17p deletion have a poor
prognosis and treatment options are limited. Venetoclax, a novel B-cell lymphoma
2 inhibitor, has been approved for treatment-experienced chronic lymphocytic
leukemia patients with the 17p deletion. A phase 1 dose-escalation study to 400
mg daily showed overall response rates across all doses of 79% with a complete
response achieved in 20%. A phase 2 multicenter open-label study demonstrated
overall response rate of 79.4% of patients (95% confidence interval 70.5-86.6)
with median duration of follow-up of 12.1 months (IQR 10.1-14.2). Tumor lysis
syndrome has been observed during initiation and titration. Assessing risk of
tumor lysis syndrome prior to therapy initiation is essential to provide
appropriate prophylactic medications. Neutropenia, potentially warranting dose
reduction or discontinuation, has been observed. Venetoclax has demonstrated
activity in other leukemias, multiple myeloma, and lymphomas. Venetoclax has
shown response, and is well tolerated in patients with highly resistant chronic
lymphocytic leukemia. It has the potential to be part of the treatment
armamentarium for other malignancies.
PMID- 28696176
TI - Interstitial lung disease following FOLFOX + FOLFIRI and bevacizumab therapy
associated with leucovorin: A case report.
AB - Chemotherapy-induced interstitial lung disease in colorectal cancer patients is
rare but represents a life-threatening adverse reaction. We report here a case of
interstitial lung disease following chemotherapy for metastatic colorectal cancer
and the interesting results of the drug-induced lymphocyte stimulation test and
leukocyte migration test. After chemotherapy with oxaliplatin plus infusional 5
fluorouracil and leucovorin (FOLFOX) plus bevacizumab followed by irinotecan plus
infusional 5-fluorouracil and leucovorin (FOLFIRI), the patient was hospitalized
with fever and chills. Laboratory data showed neutropenia and eosinophilia.
Computed tomography revealed ground-glass opacities in both lungs; therefore, we
diagnosed chemotherapy-induced interstitial lung disease. Steroid therapy was
effective. We suspected irinotecan to be the etiological drug for interstitial
lung disease in this patient because interstitial lung disease developed after
switching the regimen from FOLFOX to FOLFIRI. However, drug-induced lymphocyte
stimulation test and leukocyte migration test results were positive for only
leucovorin and negative for irinotecan and 5-fluorouracil. This is the first case
to show positive results on the drug-induced lymphocyte stimulation test and
leukocyte migration test for only leucovorin and negative results for
antineoplastic drugs. Our findings suggest that all drugs included in
chemotherapy regimens have the potential to induce interstitial lung disease, and
if rechallenge chemotherapy is considered, the drug-induced lymphocyte
stimulation test and leukocyte migration test are expected to be useful for
determining the drug that needs to be excluded.
PMID- 28696177
TI - Are prematurity and environmental factors determinants for developing childhood
onset systemic lupus erythematosus?
AB - OBJECTIVE: The objective of this study is to evaluate the influence of exposure
to air pollutants and inhalable environmental elements during pregnancy and after
birth until childhood-onset systemic lupus erythematosus(cSLE) diagnosis.
METHODS: This case-control study comprised 30 cSLE patients and 86 healthy
controls living in the Sao Paulo metropolitan area. A structured and reliable
questionnaire (kappa index for test-retest was 0.78) assessed demographic data,
gestational and perinatal-related-factors, and exposure to inhalable elements
during pregnancy and after birth (occupational exposure to inhalable particles
and/or volatile vapor, and/or tobacco, as well as, the presence of industrial
activities or gas stations near the home/work/daycare/school). Tropospheric
pollutants included: particulate matter (PM10), sulfur dioxide (SO2), nitrogen
dioxide (NO2), ozone (O3) and carbon monoxide (CO). RESULTS: The median current
age was similar between cSLE patients and healthy controls [16.0 (5-21) versus
15.0 (4-21) years, p = .32], likewise the frequency of female gender (87% versus
78%, p = .43). The frequencies of prematurity (30% versus 6%, p = .001), maternal
occupational exposure during pregnancy (59% versus 12%, p < .001), exposure to
volatile vapor (48% versus 8%, p < .001) and fetal smoking (maternal and/or
secondhand) (37% versus 19%, p = .008) were significantly higher in cSLE patients
compared with controls. In a multivariate analysis regarding the gestation
period, maternal occupational exposure (OR 13.5, 95% CI 2.5-72.4, p = .002),
fetal smoking (OR 8.6, 95%CI 1.6-47, p = .013) and prematurity (OR 15.8, 95%CI
1.9-135.3, p = .012) remained risk factors for cSLE development. Furthermore,
exposure to secondhand smoking during pregnancy and after birth (OR 9.1, 95%CI
1.8-42.1, p = .002) was also a risk factor for cSLE development. CONCLUSIONS:
Prematurity and environmental factors were risk factors for developing cSLE.
PMID- 28696178
TI - A cheat sheet to navigate the complex maze of pharmaceutical exclusivities in
Europe.
AB - As the two leading markets for pharmaceutical and biotech companies, the USA and
Europe offer incentives to stimulate drug innovation, including patent and
regulatory exclusivities. These exclusivities extend periods during which
companies can market their products free of generic or other competition and
recoup their investment. Pharmaceutical and biotech companies should carefully
assess the different types of exclusivities available when developing regulatory
submissions, patent filing strategies. The authors have previously summarized the
USA exclusivities in an earlier publication. This article focuses on European
exclusivities. Due to space limitations, it focuses on small molecule drugs.
Analogously to the format previously used, we have provided a cheat sheet of
European exclusivities for small molecule drugs in Figure 1 .
PMID- 28696179
TI - Insights into the crystal structure of BRD2-BD2 - phenanthridinone complex and
theoretical studies on phenanthridinone analogs.
AB - Bromodomain and extra-terminal family proteins recognize the acetylated histone
code on chromatin and participate in downstream processes like DNA replication,
modification, and repair. As part of epigenetic approaches, BRD2 and BRD4 were
identified as putative targets, for the management of chronic diseases. We have
recently reported the discovery of a new scaffold of the phenanthridinone-based
inhibitor (L10) of the second bromodomain of BRD2 (BRD2-BD2). Here, we present
the crystal structure of the BRD2-BD2, refined to 1.4 A resolution, in complex
with beta-mercaptoethanol (a component of the protein buffer). The beta
mercaptoethanol covalently links to C425 of BD2 in the acetyl-lysine binding
pocket, to form a modified cysteine mercaptoethanol (CME). The CME modification
significantly hinders the entry of ligands into the BD2 binding pocket,
suggesting that beta-mercaptoethanol should be removed during protein production
process. Next, to confirm whether phenanthridionone scaffold is a new inhibitor
family of BRD2-BD2, we have determined the crystal structure of BD2 in complex
with 6(5H)-Phenanthridinone (a core moiety of L10), refined to 1.28 A resolution.
It confirmed that the phenanthridinone molecule, unambiguously, binds to BD2.
Moreover, we performed molecular docking and molecular dynamic studies on
selected phenanthridinone analogs. The predicted L10 analogs are stable with
essential hydrophobic and hydrophilic interactions with BD2 during molecular
dynamic simulations. We propose that the predicted phenanthridinone analogs may
be potential molecules for inhibiting the BD2 function of acetylated histone
recognition.
PMID- 28696180
TI - Epithelial Na+ channel inhibitors for the treatment of cystic fibrosis.
AB - The epithelial Na+ channel (ENaC) is a key regulator of the volume of airway
surface liquid (ASL) and is found in the human airway epithelium. In cystic
fibrosis (CF), Na+ hyperabsorption through ENaC, in the absence of cystic
fibrosis transmembrane conductance regulator mediated anion secretion, results in
the dehydration of respiratory secretions and the impairment of mucociliary
clearance. The hypothesis of utilizing an ENaC blocking molecule to facilitate
restoration of the airway surface liquid volume sufficiently to allow normal
mucociliary clearance is of interest in the management of lung disease in CF
patients. This review summarizes the published patent applications from 2014 to
the end of 2016 that claim approaches to inhibit the function of ENaC for the
treatment of CF.
PMID- 28696181
TI - Growth factor sequestration and enzyme-mediated release from genipin-crosslinked
gelatin microspheres.
AB - Controlled release of growth factors allows the efficient, localized, and
temporally-optimized delivery of bioactive molecules to potentiate natural
physiological processes. This concept has been applied to treatments for
pathological states, including chronic degeneration, wound healing, and tissue
regeneration. Peptide microspheres are particularly suited for this application
because of their low cost, ease of manufacture, and interaction with natural
remodeling processes active during healing. The present study characterizes
gelatin microspheres for the entrapment and delivery of growth factors, with a
focus on tailored protein affinity, loading capacity, and degradation-mediated
release. Genipin crosslinking in PBS and CHES buffers produced average
microsphere sizes ranging from 15 to 30 microns with population distributions
ranging from about 15 to 60 microns. Microsphere formulations were chosen based
on properties important for controlled transient and spatial delivery, including
size, consistency, and stability. The microsphere charge affinity was found to be
dependent on gelatin type, with type A (GelA) carriers consistently having a
lower negative charge than equivalent type B (GelB) carriers. A higher degree of
crosslinking, representative of primary amine consumption, resulted in a greater
negative net charge. Gelatin type was found to be the strongest determinant of
degradation, with GelA carriers degrading at higher rates versus similarly
crosslinked GelB carriers. Growth factor release was shown to depend upon
microsphere degradation by proteolytic enzymes, while microspheres in inert
buffers showed long-term retention of growth factors. These studies illuminate
fabrication and processing parameters that can be used to control spatial and
temporal release of growth factors from gelatin-based microspheres.
PMID- 28696182
TI - Prediction of Psychiatric Hospitalization, Diagnoses, Arrests, and Violent
Behavior Through Scored Drawings and Associations.
AB - The article presents a completely empirical approach to using drawings and
associations as a supplemental tool in forensic psychological assessment. The
present system represents a modern alternative to prior theory-driven "projective
technique" approaches that have failed to pass scientific scrutiny. Using an
archival sample of 252 forensic cases, House-Tree-Person drawing protocols were
scored according to preliminary test items developed from published handbooks,
academic courses, and workshops on the use of drawings and related associations
for assessment. Intermediate test items were selected according to their being
significantly correlated with at least one external psychometric, behavioral, or
clinical variable. Psychometric and editorial considerations guided the
development of a final set of 66 test items. A "flagged for pathology" approach
demonstrated modest convergent and discriminant validity for the final set of
test items against clinical criteria on an independent sample of 150 cases of the
same type used in the preliminary item development phase. Included are sample
items and discussion of psychometric issues in working with this class of data.
PMID- 28696183
TI - Visual System Involvement in Patients with Newly Diagnosed Parkinson Disease.
AB - Purpose To assess intracranial visual system changes of newly diagnosed Parkinson
disease in drug-naive patients. Materials and Methods Twenty patients with newly
diagnosed Parkinson disease and 20 age-matched control subjects were recruited.
Magnetic resonance (MR) imaging (T1-weighted and diffusion-weighted imaging) was
performed with a 3-T MR imager. White matter changes were assessed by exploring a
white matter diffusion profile by means of diffusion-tensor imaging-based
parameters and constrained spherical deconvolution-based connectivity analysis
and by means of white matter voxel-based morphometry (VBM). Alterations in
occipital gray matter were investigated by means of gray matter VBM. Morphologic
analysis of the optic chiasm was based on manual measurement of regions of
interest. Statistical testing included analysis of variance, t tests, and
permutation tests. Results In the patients with Parkinson disease, significant
alterations were found in optic radiation connectivity distribution, with
decreased lateral geniculate nucleus V2 density (F, -8.28; P < .05), a
significant increase in optic radiation mean diffusivity (F, 7.5; P = .014), and
a significant reduction in white matter concentration. VBM analysis also showed a
significant reduction in visual cortical volumes (P < .05). Moreover, the
chiasmatic area and volume were significantly reduced (P < .05). Conclusion The
findings show that visual system alterations can be detected in early stages of
Parkinson disease and that the entire intracranial visual system can be involved.
(c) RSNA, 2017 Online supplemental material is available for this article.
PMID- 28696185
TI - In vitro evaluation of antisense oligonucleotide functionalized core-shell
nanoparticles loaded with alpha-tocopherol succinate.
AB - Antisense oligonucleotide (ASO)-conjugated-alpha-tocopherol succinate (TCS)
loaded-poly(lactic acid)-g-poly(ethylene glycol) nanoparticles (ASO-TCS-PLA-PEG
NPs), with the ratio of polymer/TCS of 10:2.5, 10:5, 10:7 (w/w) were prepared for
targeting cancer therapy. The amphiphilic PLA, amino terminated PEG graft
copolymers were synthesized by ring opening polymerization reaction.
Nanoparticles were produced by using double emulsion (w/o/w) solvent evaporation
method. ASO-TCS-PLA-PEG NPs demonstrated satisfactory encapsulation and loading
efficiency and size distribution. The short-term stability studies were carried
out at 4 and 25 degrees C for 30 days to assess their mean particle size,
polydispersity index and zeta potential. The cellular uptake and extended
cytoplasmic retention of the NPs in A549 human lung carcinoma and L929 mouse
fibroblast cells were examined by fluorescence and confocal microscopy. In human
lung cancer cells, ASO-TCS-PLA-PEG NPs exhibited better cellular internalization,
cytotoxicity and apoptotic and necrotic effects compared to healthy cell line,
L929. These findings showed that ASO-modified nanoparticles could serve as a
promising nanocarrier for targeted tumor cells.
PMID- 28696184
TI - Insurance Coverage for CT Colonography Screening: Impact on Overall Colorectal
Cancer Screening Rates.
AB - Purpose To compare overall colorectal cancer (CRC) screening rates for patients
who were eligible and due for CRC screening and who were with and without
insurance coverage for computed tomographic (CT) colonography for CRC screening.
Materials and Methods The institutional review board approved this retrospective
cohort study, with a waiver of consent. This study used longitudinal electronic
health record data from 2005 through 2010 for patients managed by one of the
largest multispecialty physician groups in the United States. It included 33 177
patients under age 65 who were eligible and due for CRC screening and managed by
the participating health system. Stratified Cox regression models provided
propensity-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for
the relationship between CT colonography coverage and CRC screening. Results
After adjustment, patients who had insurance coverage for CT colonography and
were due for CRC screening had a 48% greater likelihood of being screened for CRC
by any method compared with those without coverage who were due for CRC screening
(HR, 1.48; 95% CI: 1.41, 1.55). Similarly, patients with CT colonography coverage
had a greater likelihood of being screened with CT colonography (HR, 8.35; 95%
CI: 7.11, 9.82) and with colonoscopy (HR, 1.38; 95% CI: 1.31, 1.45) but not with
fecal occult blood test (HR, 1.00; 95% CI: 0.91, 1.10) than those without such
insurance coverage. Conclusion Insurance coverage of CT colonography for CRC
screening was associated with a greater likelihood of a patient being screened
and a greater likelihood of being screened with a test that helps both to detect
cancer and prevent cancer from developing (CT colonography or colonoscopy). (c)
RSNA, 2017.
PMID- 28696186
TI - Detection of Babesia DNA in blood and spleen samples from Eurasian badgers (Meles
meles) in Scotland.
AB - Babesia are intraerythrocytic parasites of importance worldwide within the fields
of human and veterinary medicine, as some Babesia sp., including Babesia microti
are potentially zoonotic and can cause fatal disease in both humans and animals.
The aims of this study were to use a nested PCR (amplifying the 18S rRNA gene) to
determine the presence and species of Babesia parasite DNA found in blood (n =
47) and spleen (n = 47) samples collected from Eurasian badgers (Meles meles) in
Scotland. The results showed 28/47 (59.6%) blood and 14/47 (29.8%) spleen samples
tested positive for the presence of Babesia DNA. Initial sequence analysis of the
Babesia DNA identified three distinct sequence types (submitted to GenBank
KX528553, KX528554 and KX528555), which demonstrated ?99% identity to Babesia sp.
parasites previously identified in badgers in Spain (KT223484 and KT223485).
Phylogenetic analysis showed that the three isolates are closely related to
Babesia annae, B. microti and other Piroplasmida species found in wildlife.
Further sequence analysis of the samples demonstrated that the badgers were
routinely infected with more than one parasite isolate and there was also
evidence of genetic recombination between the Babesia parasite isolates
(submitted to GenBank KY250472 - KY250477).
PMID- 28696188
TI - Evolution of cross-neutralizing antibodies and mapping epitope specificity in
plasma of chronic HIV-1-infected antiretroviral therapy-naive children from
India.
AB - Delineating the factors leading to the development of broadly neutralizing
antibodies (bnAbs) during natural HIV-1 infection and dissecting their epitope
specificities generates useful information for vaccine design. This is the first
longitudinal study to assess the plasma-neutralizing antibody response and
neutralizing determinants in HIV-1-infected children from India. We enrolled 26
and followed up 20 antiretroviral therapy (ART)-naive, asymptomatic, chronic HIV
1-infected children. Five (19.2 %) baseline and 10 (50 %) follow-up plasma
samples neutralized >=50 % of subtypes A, B and C tier 2 viruses at an ID50 titre
>=150. A modest improvement in neutralization breadth and potency was observed
with time. At baseline, subtype C-specific neutralization predominated (P=0.026);
interestingly, follow-up samples exhibited cross-neutralizing activity. Epitope
mapping revealed V3C reactive antibodies with significantly increased Max50
binding titres in follow-up samples from five infected children; patient #4's
plasma antibodies exhibited V3-directed neutralization. A salient observation was
the presence of CD4 binding site (CD4bs)-specific NAbs in patient #18 that
improved with time (1.76-fold). The RSC3 wild-type (RSC3WT) protein-depleted
plasma eluate of patient #18 demonstrated a more than 50% ID50 decrease in
neutralization capacity against five HIV-1 pseudoviruses. Further, the presence
of CD4bs-neutralizing determinants in patient #18's plasma was confirmed by the
neutralizing activity demonstrated by the CD4bs-directed IgG fraction purified
from this plasma, and competition with sCD4 against JRFLgp120, identifying this
paediatric donor as a potential candidate for the isolation of CD4bs-directed
bnAbs. Overall, we observed a relative increase in plasma-neutralizing activity
with time in HIV-1-infected children, which suggests that the bnAbs evolve.
PMID- 28696189
TI - Appropriate diagnosis of tickborne infections.
PMID- 28696187
TI - DprA from Neisseria meningitidis: properties and role in natural competence for
transformation.
AB - DNA processing chain A (DprA) is a DNA-binding protein that is ubiquitous in
bacteria and expressed in some archaea. DprA is active in many bacterial species
that are competent for transformation of DNA, but its role in
Neisseriameningitidis (Nm) is not well characterized. An Nm mutant lacking DprA
was constructed, and the phenotypes of the wild-type and DeltadprA mutant were
compared. The salient feature of the phenotype of dprA null cells is the total
lack of competence for genetic transformation shown by all of the donor DNA
substrates tested in this study. Here, Nm wild-type and dprA null cells appeared
to be equally resistant to genotoxic stress. The gene encoding DprANm was cloned
and overexpressed, and the biological activities of DprANm were further
investigated. DprANm binds ssDNA more strongly than dsDNA, but lacks DNA uptake
sequence-specific DNA binding. DprANm dimerization and interaction with the C
terminal part of the single-stranded binding protein SSBNmwere demonstrated. dprA
is co-expressed with smg, a downstream gene of unknown function, and the gene
encoding topoisomerase 1, topA.
PMID- 28696190
TI - Syphilis 100 years later: Another lost opportunity?
PMID- 28696191
TI - Labels matter: Challenging conversations or challenging people?
PMID- 28696192
TI - Breast cancer screening: Does tomosynthesis augment mammography?
AB - Digital breast tomosynthesis (DBT) is a relatively new imaging technology that is
being adopted widely for breast cancer screening. Initial evidence suggests that
it may reduce recall rates and increase cancer detection rates when added to
digital mammography screening. However, more rigorous, prospective studies are
needed to determine whether it improves long-term clinical outcomes of breast
cancer screening.
PMID- 28696193
TI - Living with hematologic cancer: Recommendations, solutions.
AB - Patients with hematologic cancers such as leukemia, lymphoma, and multiple
myeloma are living longer than ever. The survival rate of patients with most
hematologic cancers has doubled since 1974, and these once-terminal diagnoses are
now chronic health conditions. This article reviews the care of patients with
hematologic cancers, including those previously treated for childhood,
adolescent, and young-adult cancers, discusses the role of primary care in a
multidisciplinary team approach, and reviews innovative ways to deliver needed
care.
PMID- 28696194
TI - Patients with challenging behaviors: Communication strategies.
AB - Some patients have behaviors that make interactions unpleasant, sometimes
contributing to suboptimal outcomes and physician burnout. Understanding common
difficult personality types can help doctors plan effective strategies for
dealing with each, resulting in more effective communication, less stress, and
better health outcomes.
PMID- 28696195
TI - Optimizing diagnostic testing for venous thromboembolism.
AB - Diagnostic algorithms for venous thromboembolism exist, but most do not provide
detailed guidance as to which patients, if any, may benefit from screening for
thrombophilia. This article provides an overview of the optimized diagnosis of
venous thromboembolism, with a focus on the appropriate use of thrombophilia
screening.
PMID- 28696196
TI - Tickborne diseases other than Lyme in the United States.
AB - Tickborne diseases are increasing in the United States, and the geographic range
of tick vectors is expanding. Tickborne diseases are challenging to diagnose, as
they present with vague symptoms such as fever, constitutional symptoms, and
nonspecific laboratory abnormalities. A high degree of clinical suspicion is
required to make a diagnosis, as patients often do not recall a tick bite. The
availability of laboratory testing for tickborne diseases is limited, especially
in the acute setting. Therefore, if a tickborne disease is suspected, empiric
therapy should often be initiated before laboratory confirmation of the disease
is available. This article summarizes the most common non-Lyme tickborne diseases
in the United States.
PMID- 28696197
TI - Swelling of both arms and chest after push-ups.
PMID- 28696198
TI - Secondary syphilis.
PMID- 28696199
TI - A large mass in the right ventricle: Tumor or thrombus?
PMID- 28696200
TI - Vaccination Coverage Among Adults Aged 65 and Over: United States, 2015.
AB - KEY FINDINGS: Data from the National Health Interview Survey ? Among adults aged
65 and over, more than two-thirds had an influenza vaccine in the past 12 months
(69.0%). ? More than one in two adults aged 65 and over had a tetanus vaccine in
the past 10 years (56.9%). ? More than 6 of 10 adults aged 65 and over had ever
had a pneumococcal vaccine (63.6%), while a little more than one-third had ever
had a shingles vaccine (34.2%). ? Among adults aged 65 and over, vaccination
coverage was highest for non-Hispanic white adults compared with non- Hispanic
black and Hispanic adults. ? Vaccination coverage was lowest among poor adults
aged 65 and over.
PMID- 28696201
TI - Sexual Activity and Contraceptive Use Among Teenagers in the United States, 2011
2015.
AB - Objective-This report presents national estimates of sexual activity and
contraceptive use among males and females aged 15-19 in the United States in 2011
2015, based on data from the National Survey of Family Growth (NSFG). For
selected indicators, data are also presented from the 1988, 1995, 2002, and 2006
2010 NSFGs, and from the 1988 and 1995 National Survey of Adolescent Males, which
was conducted by the Urban Institute. Methods-NSFG data were collected through in
person interviews with nationally representative samples of men and women aged 15
44 in the household population of the United States. NSFG 2011-2015 interviews
were conducted between September 2011 and September 2015 with 20,621 men and
women, including 4,134 teenagers (2,047 females and 2,087 males). The response
rate was 72.5% for male teenagers and 73.0% for female teenagers. Results-In 2011
2015, 42.4% of never-married female teenagers (4.0 million) and 44.2% of never
married male teenagers (4.4 million) had had sexual intercourse at least once by
the time of the interview (were sexually experienced). These levels of sexual
experience among teenagers are similar to those seen in 2002 and 2006-2010 data.
Longer-term trends, from 1988 to 2011-2015, show declines in the percentage of
teenagers who were sexually experienced. Female teenagers' use of a method of
contraception at first sex increased from 74.5% in 2002 to 81.0% in 2011-2015.
Male teenagers' use of a condom at first sex increased from 70.9% in 2002 to
79.6% in 2006-2010 and remained stable at 76.8% in 2011-2015. Overall, in 2011
2015, 5.8% of female teenagers had used a long-acting reversible method
(intrauterine device or implant).
PMID- 28696202
TI - Animal models for personalized treatment options.
PMID- 28696203
TI - A broadly distributed toxin family mediates contact-dependent antagonism between
gram-positive bacteria.
AB - The Firmicutes are a phylum of bacteria that dominate numerous polymicrobial
habitats of importance to human health and industry. Although these communities
are often densely colonized, a broadly distributed contact-dependent mechanism of
interbacterial antagonism utilized by Firmicutes has not been elucidated. Here we
show that proteins belonging to the LXG polymorphic toxin family present in
Streptococcus intermedius mediate cell contact- and Esx secretion pathway
dependent growth inhibition of diverse Firmicute species. The structure of one
such toxin revealed a previously unobserved protein fold that we demonstrate
directs the degradation of a uniquely bacterial molecule required for cell wall
biosynthesis, lipid II. Consistent with our functional data linking LXG toxins to
interbacterial interactions in S. intermedius, we show that LXG genes are
prevalent in the human gut microbiome, a polymicrobial community dominated by
Firmicutes. We speculate that interbacterial antagonism mediated by LXG toxins
plays a critical role in shaping Firmicute-rich bacterial communities.
PMID- 28696204
TI - LTP and memory impairment caused by extracellular Abeta and Tau oligomers is APP
dependent.
AB - The concurrent application of subtoxic doses of soluble oligomeric forms of human
amyloid-beta (oAbeta) and Tau (oTau) proteins impairs memory and its
electrophysiological surrogate long-term potentiation (LTP), effects that may be
mediated by intra-neuronal oligomers uptake. Intrigued by these findings, we
investigated whether oAbeta and oTau share a common mechanism when they impair
memory and LTP in mice. We found that as already shown for oAbeta, also oTau can
bind to amyloid precursor protein (APP). Moreover, efficient intra-neuronal
uptake of oAbeta and oTau requires expression of APP. Finally, the toxic effect
of both extracellular oAbeta and oTau on memory and LTP is dependent upon APP
since APP-KO mice were resistant to oAbeta- and oTau-induced defects in
spatial/associative memory and LTP. Thus, APP might serve as a common therapeutic
target against Alzheimer's Disease (AD) and a host of other neurodegenerative
diseases characterized by abnormal levels of Abeta and/or Tau.
PMID- 28696205
TI - Increasing evidence of mechanical force as a functional regulator in smooth
muscle myosin light chain kinase.
AB - Mechanosensitive proteins are key players in cytoskeletal remodeling, muscle
contraction, cell migration and differentiation processes. Smooth muscle myosin
light chain kinase (smMLCK) is a member of a diverse group of serine/threonine
kinases that feature cytoskeletal association. Its catalytic activity is
triggered by a conformational change upon Ca2+/calmodulin (Ca2+/CaM) binding. Due
to its significant homology with the force-activated titin kinase, smMLCK is
suspected to be also regulatable by mechanical stress. In this study, a CaM
independent activation mechanism for smMLCK by mechanical release of the
inhibitory elements is investigated via high throughput AFM single-molecule force
spectroscopy. The characteristic pattern of transitions between different smMLCK
states and their variations in the presence of different substrates and ligands
are presented. Interaction between kinase domain and regulatory light chain (RLC)
substrate is identified in the absence of CaM, indicating restored substrate
binding capability due to mechanically induced removal of the auto-inhibitory
regulatory region.
PMID- 28696206
TI - Beyond scoops to best practices.
AB - Authors submitting a manuscript to eLife are encouraged to upload it to a
recognized preprint server at the same time in order to make their results
available as quickly and as widely as possible.
PMID- 28696207
TI - Levels and Determinants of DDT and DDE Exposure in the VHEMBE Cohort.
AB - BACKGROUND: Although indoor residual spraying (IRS) is an effective tool for
malaria control, its use contributes to high insecticide exposure in sprayed
communities and raises concerns about possible unintended health effects.
OBJECTIVE: The Venda Health Examination of Mothers, Babies and their Environment
(VHEMBE) is a birth cohort study initiated in 2012 to characterize prenatal
exposure to IRS insecticides and exposures' impacts on child health and
development in rural South Africa. METHODS: In this report, we describe the
VHEMBE cohort and dichlorodiphenyltrichloroethane (DDT) and
dichlorodiphenyldichloroethylene (DDE) serum concentrations measured in VHEMBE
mothers when they presented for delivery. In addition, we applied a causal
inference framework to estimate the potential reduction in population-level p,p'
DDT and p,p'-DDE serum concentrations under five hypothetical interventions. A
total of 751 mothers were enrolled. RESULTS: Serum concentrations of p,p' isomers
of DDT and DDE were above the limit of detection (LOD) in >=98% of the samples,
whereas the o,p' isomers were above the LOD in at least 80% of the samples.
Median (interquartile range) p,p'-DDT and p,p'-DDE serum concentrations for
VHEMBE cohort participants were 55.3 (19.0-259.3) and 242.2 (91.8-878.7) ng/g
lipid, respectively. Mothers reporting to have lived in a home sprayed with DDT
for malaria control had ~5-7 times higher p,p'-DDT and p,p'-DDE serum
concentrations than those who never lived in a home sprayed with DDT. Of the five
potential interventions tested, we found increasing access to water significantly
reduced p,p'-DDT exposure and increasing the frequency of household wet mopping
significantly reduced p,p'-DDT and p,p'-DDE exposure. CONCLUSION: Our findings
suggest that several intervention approaches may reduce DDT/DDE exposure in
pregnant women living in IRS communities. https://doi.org/10.1289/EHP353.
PMID- 28696208
TI - Effects of Coal Fly Ash Particulate Matter on the Antimicrobial Activity of
Airway Surface Liquid.
AB - BACKGROUND: Sustained exposure to ambient particulate matter (PM) is a global
cause of mortality. Coal fly ash (CFA) is a byproduct of coal combustion and is a
source of anthropogenic PM with worldwide health relevance. The airway epithelia
are lined with fluid called airway surface liquid (ASL), which contains
antimicrobial proteins and peptides (AMPs). Cationic AMPs bind negatively charged
bacteria to exert their antimicrobial activity. PM arriving in the airways could
potentially interact with AMPs in the ASL to affect their antimicrobial activity.
OBJECTIVES: We hypothesized that PM can interact with ASL AMPs to impair their
antimicrobial activity. METHODS: We exposed pig and human airway explants, pig
and human ASL, and the human cationic AMPs beta-defensin-3, LL-37, and lysozyme
to CFA or control. Thereafter, we assessed the antimicrobial activity of exposed
airway samples using both bioluminescence and standard colony-forming unit
assays. We investigated PM-AMP electrostatic interaction by attenuated total
reflection Fourier-transform infrared spectroscopy and measuring the zeta
potential. We also studied the adsorption of AMPs on PM. RESULTS: We found
increased bacterial survival in CFA-exposed airway explants, ASL, and AMPs. In
addition, we report that PM with a negative surface charge can adsorb cationic
AMPs and form negative particle-protein complexes. CONCLUSION: We propose that
when CFA arrives at the airway, it rapidly adsorbs AMPs and creates negative
complexes, thereby decreasing the functional amount of AMPs capable of killing
pathogens. These results provide a novel translational insight into an early
mechanism for how ambient PM increases the susceptibility of the airways to
bacterial infection. https://doi.org/10.1289/EHP876.
PMID- 28696209
TI - Hashimoto's thyroiditis predicts outcome in intrathyroidal papillary thyroid
cancer.
AB - Hashimoto's thyroiditis (HT) seems to have favourable prognostic impact on
papillary thyroid cancer (PTC), but data were obtained analysing all disease
stages. Given that HT-related microenvironment involves solely the thyroid, we
aimed to assess the relationship between HT, as detected through pathological
assessment, and outcome in intrathyroidal PTC. This was a multicentre,
retrospective, observational study including 301 PTC with no evidence of
extrathyroidal disease. Primary study endpoint was the rate of clinical
remission. Auxiliary endpoint was recurrence-free survival (RFS). HT was detected
in 42.5% of the cohort and was associated to female gender, smaller tumour size,
lower rate of aggressive PTC variants and less frequent post-surgery radio-iodine
administration. HT showed relationship with significantly higher rate of clinical
remission (P < 0.001, OR 4, 95% CI 1.78-8.94). PTCs with concomitant HT had
significantly longer RFS, as compared with non-HT tumours (P = 0.004). After
adjustment for other parameters affecting disease outcome at univariate analysis
(age at diagnosis, histology, tumour size and multifocality), prognostic effect
of HT remained significant (P = 0.006, OR 3.28, 95% CI 1.39-7.72). To verify
whether HT could optimise the identification of PTCs with unfavourable outcome,
we assessed the accuracy of 'non-HT status' as negative prognostic marker,
demonstrating poor capability of identifying patients not maintaining clinical
remission until final follow-up (probability of no clinical remission in PTCs
without HT: 21.05%, 95% CI 15.20-27.93). In conclusion, our data show that HT
represents an independent prognostic parameter in intrathyroidal PTC, but cannot
improve prognostic specificity.
PMID- 28696210
TI - Role of chromosomal instability in cancer progression.
AB - Cancer cells often display chromosomal instability (CIN), a defect that involves
loss or rearrangement of the cell's genetic material - chromosomes - during cell
division. This process results in the generation of aneuploidy, a deviation from
the haploid number of chromosomes, and structural alterations of chromosomes in
over 90% of solid tumours and many haematological cancers. This trait is unique
to cancer cells as normal cells in the body generally strictly maintain the
correct number and structure of chromosomes. This key difference between cancer
and normal cells has led to two important hypotheses: (i) cancer cells have had
to overcome inherent barriers to changes in chromosomes that are not tolerated in
non-cancer cells and (ii) CIN represents a cancer-specific target to allow the
specific elimination of cancer cells from the body. To exploit these hypotheses
and design novel approaches to treat cancer, a full understanding of the
mechanisms driving CIN and how CIN contributes to cancer progression is required.
Here, we will discuss the possible mechanisms driving chromosomal instability,
how CIN may contribute to the progression at multiple stages of tumour evolution
and possible future therapeutic directions based on targeting cancer chromosomal
instability.
PMID- 28696211
TI - Rab8a Deficiency in Skeletal Muscle Causes Hyperlipidemia and Hepatosteatosis by
Impairing Muscle Lipid Uptake and Storage.
AB - Skeletal muscle absorbs long-chain fatty acids (LCFAs) that are either oxidized
in mitochondria or temporarily stored as triglycerides in lipid droplets (LDs).
So far, it is still not fully understood how lipid uptake and storage are
regulated in muscle and whether these are important for whole-body lipid
homeostasis. Here we show that the small GTPase Rab8a regulates lipid uptake and
storage in skeletal muscle. Muscle-specific Rab8a deletion caused hyperlipidemia
and exacerbated hepatosteatosis induced by a high-fat diet. Mechanistically,
Rab8a deficiency decreased LCFA entry into skeletal muscle and inhibited LD
fusion in muscle cells. Consequently, blood lipid levels were elevated and
stimulated hepatic mammalian target of rapamycin, which enhanced hepatosteatosis
by upregulating hepatic lipogenesis and cholesterol biosynthesis. Our results
demonstrate the significance of lipid uptake and storage in muscle in regulating
whole-body lipid homeostasis, and they shed light on the roles of skeletal muscle
in the pathogenesis of hyperlipidemia and hepatosteatosis.
PMID- 28696212
TI - Compound heterozygous SLC19A3 mutations further refine the critical promoter
region for biotin-thiamine-responsive basal ganglia disease.
AB - Mutations in the gene SLC19A3 result in thiamine metabolism dysfunction syndrome
2, also known as biotin-thiamine-responsive basal ganglia disease (BTBGD). This
neurometabolic disease typically presents in early childhood with progressive
neurodegeneration, including confusion, seizures, and dysphagia, advancing to
coma and death. Treatment is possible via supplement of biotin and/or thiamine,
with early treatment resulting in significant lifelong improvements. Here we
report two siblings who received a refined diagnosis of BTBGD following whole
genome sequencing. Both children inherited compound heterozygous mutations from
unaffected parents; a missense single-nucleotide variant (p.G23V) in the first
transmembrane domain of the protein, and a 4808-bp deletion in exon 1
encompassing the 5' UTR and minimal promoter region. This deletion is the
smallest promoter deletion reported to date, further defining the minimal
promoter region of SLC19A3 Unfortunately, one of the siblings died prior to
diagnosis, but the other is showing significant improvement after commencement of
therapy. This case demonstrates the power of whole-genome sequencing for the
identification of structural variants and subsequent diagnosis of rare
neurodevelopmental disorders.
PMID- 28696213
TI - Ca2+ Regulation of Cav3.3 T-type Ca2+ Channel Is Mediated by Calmodulin.
AB - Calcium-dependent inactivation of high voltage-activated Ca2+ channels plays a
crucial role in limiting rises in intracellular calcium (Ca2+i). A key mediator
of these effects is calmodulin, which has been found to bind the C-terminus of
the pore-forming alpha subunit. In contrast, little is known about how Ca2+i can
regulate low voltage-activated T-type Ca2+ channels. Using whole cell patch
clamp, we examined the biophysical properties of Ca2+ current through the three T
type Ca2+ channel isoforms, Cav3.1, Cav3.2, or Cav3.3, comparing internal
solutions containing 27 nM and l MUM free Ca2+ Both activation and inactivation
kinetics of Cav3.3 current in l MUM Ca2+i solution were more rapid than those in
27 nM Ca2+i solution. In addition, both activation and steady-state inactivation
curves of Cav3.3 were negatively shifted in the higher Ca2+i solution. In
contrast, the biophysical properties of Cav3.1 and Cav3.2 isoforms were not
significantly different between the two internal solutions. Overexpression of
CaM1234 (a calmodulin mutant that doesn't bind Ca2+) occluded the effects of l
MUM Ca2+i on Cav3.3, implying that CaM is involved in the Ca2+i regulation
effects on Cav3.3. Yeast two-hybrid screening and co-immunoprecipitation
experiments revealed a direct interaction of CaM with the carboxyl terminus of
Cav3.3. Taken together, our results suggest that Cav3.3 T-type channel is
potently regulated by Ca2+i via interaction of Ca2+/CaM with the carboxyl
terminus of Cav3.3.
PMID- 28696214
TI - Epigenetic Regulation by Agonist-Specific Aryl Hydrocarbon Receptor Recruitment
of Metastasis-Associated Protein 2 Selectively Induces Stanniocalcin 2
Expression.
AB - The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor
that regulates a plethora of target genes. Historically, the AhR has been studied
as a regulator of xenobiotic metabolizing enzyme genes, notably cytochrome
P4501A1 encoded by CYP1A1, in response to the exogenous prototypical ligand
2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). AhR activity depends on its binding
to the xenobiotic response element (XRE) in partnership with the AhR nuclear
translocator (Arnt). Recent studies identified stanniocalcin 2 (Stc2) as a novel
AhR target gene responsive to the endogenous AhR agonist cinnabarinic acid (CA).
CA-dependent AhR-XRE-mediated Stc2 upregulation is responsible for cytoprotection
against ectoplasmic reticulum/oxidative stress-induced apoptosis both in vitro
and in vivo. Significantly, CA but not TCDD induces expression of Stc2 in
hepatocytes. In contrast to TCDD, CA is unable to induce the CYP1A1 gene, thus
revealing an AhR agonist-specific mutually exclusive dichotomous transcriptional
response. Studies reported here provide a mechanistic explanation for this
differential response by identifying an interaction between the AhR and the
metastasis-associated protein 2 (MTA2). Moreover, the AhR-MTA2 interaction is CA
dependent and results in MTA2 recruitment to the Stc2 promoter, concomitant with
agonist-specific epigenetic modifications targeting histone H4 lysine
acetylation. The results demonstrate that histone H4 acetylation is absolutely
dependent on CA-induced AhR and MTA2 recruitment to the Stc2 regulatory region
and induced Stc2 gene expression, which in turn confers cytoprotection to liver
cells exposed to chemical insults.
PMID- 28696215
TI - A Model for Epigenetic Inhibition via Transvection in the Mouse.
AB - Transvection is broadly defined as the ability of one locus to affect its
homologous locus in trans Although it was first discovered in the 1950s, there
are only two known cases in mammals. Here, we report another instance of
mammalian transvection induced by the Cre/LoxP system, which is widely used for
conditional gene targeting in the mouse. We attempted to use the germline
expressed Vasa-Cre transgene to engineer a mouse mutation, but observe a dramatic
reduction of LoxP recombination in mice that inherit an already deleted LoxP
allele in trans A similar phenomenon has previously been observed with another
Cre that is expressed during meiosis: Sycp-1-Cre This second example of LoxP
inhibition in trans reinforces the conclusion that certain meiotically expressed
Cre alleles can initiate transvection in mammals. However, unlike the previous
example, we find that the inhibition of LoxP recombination is not due to DNA
methylation. In addition, we demonstrate that LoxP inhibition is easily
alleviated by adding an extra generation to our crossing scheme. This finding
confirms that the LoxP sites are inhibited via an epigenetic mechanism, and
provides a method for the use of other Cre transgenes associated with a similar
LoxP inhibition event. Furthermore, the abrogation of LoxP inhibition by the
simple addition of an extra generation in our crosses establishes a unique mouse
system for future studies to uncover the mechanism of transvection in mammals.
PMID- 28696216
TI - Regulation of Lysosomal Function by the DAF-16 Forkhead Transcription Factor
Couples Reproduction to Aging in Caenorhabditis elegans.
AB - Aging in eukaryotes is accompanied by widespread deterioration of the somatic
tissue. Yet, abolishing germ cells delays the age-dependent somatic decline in
Caenorhabditis elegans In adult worms lacking germ cells, the activation of the
DAF-9/DAF-12 steroid signaling pathway in the gonad recruits DAF-16 activity in
the intestine to promote longevity-associated phenotypes. However, the impact of
this pathway on the fitness of normally reproducing animals is less clear. Here,
we explore the link between progeny production and somatic aging and identify the
loss of lysosomal acidity-a critical regulator of the proteolytic output of these
organelles-as a novel biomarker of aging in C. elegans The increase in lysosomal
pH in older worms is not a passive consequence of aging, but instead is timed
with the cessation of reproduction, and correlates with the reduction in
proteostasis in early adult life. Our results further implicate the steroid
signaling pathway and DAF-16 in dynamically regulating lysosomal pH in the
intestine of wild-type worms in response to the reproductive cycle. In the
intestine of reproducing worms, DAF-16 promotes acidic lysosomes by upregulating
the expression of v-ATPase genes. These findings support a model in which protein
clearance in the soma is linked to reproduction in the gonad via the active
regulation of lysosomal acidification.
PMID- 28696217
TI - Exact Calculation of the Joint Allele Frequency Spectrum for Isolation with
Migration Models.
AB - Population genomic datasets collected over the past decade have spurred interest
in developing methods that can utilize massive numbers of loci for inference of
demographic and selective histories of populations. The allele frequency spectrum
(AFS) provides a convenient statistic for such analysis, and, accordingly, much
attention has been paid to predicting theoretical expectations of the AFS under a
number of different models. However, to date, exact solutions for the joint AFS
of two or more populations under models of migration and divergence have not been
found. Here, we present a novel Markov chain representation of the coalescent on
the state space of the joint AFS that allows for rapid, exact calculation of the
joint AFS under isolation with migration (IM) models. In turn, we show how our
Markov chain method, in the context of composite likelihood estimation, can be
used for accurate inference of parameters of the IM model using SNP data. Lastly,
we apply our method to recent whole genome datasets from African Drosophila
melanogaster.
PMID- 28696219
TI - Imaging-Based Simulations for Predicting Sudden Death and Guiding Ventricular
Tachycardia Ablation.
PMID- 28696218
TI - Noncanonical Decapentaplegic Signaling Activates Matrix Metalloproteinase 1 To
Restrict Hedgehog Activity and Limit Ectopic Eye Differentiation in Drosophila.
AB - One of the pertinent issues associated with cellular plasticity is to understand
how the delicate balance between the determined state of cells and the extent to
which they can transdetermine is maintained. Employing the well-established model
of generating ectopic eyes in developing wing discs of Drosophila by ectopic
eyeless expression, we provide evidence for the genetic basis of this mechanism.
By both loss-of-function and gain-of-function genetic analyses, we demonstrate
that Matrix metalloproteinase 1 (Mmp1) plays an important role in regulating the
extent of ectopic ommatidial differentiation. Transcriptional activation of
ectopic Mmp1 by the morphogen Decapentaplegic (Dpp) is not triggered by its
canonical signaling pathway which involves Mad. Rather, Dpp activates an
alternate cascade involving dTak1 and JNK, to induce ectopic Mmp1 expression.
Mutational analyses reveal that Mmp1 negatively regulates ectopic eye
differentiation by restricting the rate of proliferation and the levels of
expression of retinal-determining genes dachshund and eyes absent This is
primarily achieved by restricting the range of Hedgehog (Hh) signaling.
Importantly, the increase in proliferation and upregulation of target retinal
determining genes, as observed upon attenuating Mmp1 activity, gets significantly
rescued when ectopic eyes are generated in wing discs of hh heterozygous mutants.
In conjunction with the previously established instructive and permissive roles
of Dpp in facilitating ectopic eye differentiation in wing discs, the outcome of
this study sheds light on a mechanism by which Dpp plays a dual role in
modulating the delicate balance between the determined state of cells and the
extent they can transdetermine.
PMID- 28696220
TI - Prevention of Sudden Cardiac Death in Adults With Congenital Heart Disease: Do
the Guidelines Fall Short?
AB - BACKGROUND: Sudden cardiac death (SCD) is a major cause of mortality in adult
congenital heart disease (ACHD) patients. SCD may be prevented by implantable
cardioverter-defibrillator (ICD) implantation, but patient stratification remains
troublesome. The 2014 Consensus Statement on Arrhythmias in ACHD patients and the
2015 European Society of Cardiology Guidelines specified recommendations for ICD
implantation in ACHD patients for the first time. We assess the discriminative
ability of these ICD recommendations for SCD in ACHD patients. METHODS AND
RESULTS: Of 25 790 ACHD patients in an international multicenter registry, we
identified all SCD cases, matched to living controls by age, sex, congenital
defect, and surgical repair. We assessed all primary prevention ICD
recommendations listed in both documents. We used conditional logistic regression
models to calculate odds ratios and receiver operating characteristic curves with
area under the curve. Consensus Statement: One hundred twenty-four cases (median
age at death, 33 years [26-44]; 67% men) and 230 controls were studied. In total,
41% of SCD cases and 17% of controls had an ICD recommendation (odds ratio, 5.9;
P<0.001). European Society of Cardiology Guidelines: Of one hundred fifty-seven
cases (median age at death, 33 years [26-48]; 64% men) and 292 controls, 35% and
14% had an ICD recommendation, respectively (odds ratio, 4.8; P<0.001).
CONCLUSIONS: A minority of SCD cases had an ICD recommendation according to these
guidelines, whereas the majority of SCD victims remained unrecognized. With an
area under the curve of 0.6 to 0.7, the discriminative ability of both guidelines
was mediocre. Critical clinical reasoning when deciding on ICD implantation in
ACHD patients, therefore, remains vital.
PMID- 28696221
TI - Meiotic Chromosome Association 1 Interacts with TOP3alpha and Regulates Meiotic
Recombination in Rice.
AB - Homologous recombination plays a central role in guaranteeing chromosome
segregation during meiosis. The precise regulation of the resolution of
recombination intermediates is critical for the success of meiosis. Many
proteins, including the RECQ DNA helicases (Sgs1/BLM) and Topoisomerase 3alpha
(TOP3alpha), have essential functions in managing recombination intermediates.
However, many other factors involved in this process remain to be defined. Here,
we report the isolation of meiotic chromosome association 1 (MEICA1), a novel
protein participating in meiotic recombination in rice (Oryza sativa). Loss of
MEICA1 leads to nonhomologous chromosome association, the formation of massive
chromosome bridges, and fragmentation. MEICA1 interacts with MSH7, suggesting its
role in preventing nonallelic recombination. In addition, MEICA1 has an
anticrossover activity revealed by suppressing the defects of crossover formation
in msh5 meica1 compared with that in msh5, showing the similar function with its
interacted protein TOP3alpha. Thus, our data establish two pivotal roles for
MEICA1 in meiosis: preventing aberrant meiotic recombination and regulating
crossover formation.
PMID- 28696222
TI - ZHOUPI and KERBEROS Mediate Embryo/Endosperm Separation by Promoting the
Formation of an Extracuticular Sheath at the Embryo Surface.
AB - Arabidopsis thaliana seed development requires the concomitant development of two
zygotic compartments, the embryo and the endosperm. Following fertilization, the
endosperm expands and the embryo grows invasively through the endosperm, which
breaks down. Here, we describe a structure we refer to as the embryo sheath that
forms on the surface of the embryo as it starts to elongate. The sheath is
deposited outside the embryonic cuticle and incorporates endosperm-derived
material rich in extensin-like molecules. Sheath production is dependent upon the
activity of ZHOUPI, an endosperm-specific transcription factor necessary for
endosperm degradation, embryo growth, embryo-endosperm separation, and normal
embryo cuticle formation. We show that the peptide KERBEROS, whose expression is
ZHOUPI dependent, is necessary both for the formation of a normal embryo sheath
and for embryo-endosperm separation. Finally, we show that the receptor-like
kinases GSO1 and GSO2 are required for sheath deposition at the embryo surface
but not for production of sheath material in the endosperm. We present a model in
which sheath formation depends on the coordinated production of material in the
endosperm and signaling within the embryo, highlighting the complex molecular
interaction between these two tissues during early seed development.
PMID- 28696223
TI - White-Coat Effect Is Uncommon in Patients With Refractory Hypertension.
AB - Refractory hypertension is a recently described phenotype of antihypertensive
treatment failure defined as uncontrolled blood pressure (BP) despite the use of
>=5 different antihypertensive agents, including chlorthalidone and
spironolactone. Recent studies indicate that refractory hypertension is uncommon,
with a prevalence of ~5% to 10% of patients referred to a hypertension specialty
clinic for uncontrolled hypertension. The prevalence of white-coat effect, that
is, uncontrolled automated office BP >=135/85 mm Hg and controlled out-of-office
BP <135/85 mm Hg, by awake ambulatory BP monitor in hypertensive patients overall
is ~30% to 40%. The prevalence of white-coat effect among patients with
refractory hypertension has not been previously reported. In this prospective
evaluation, consecutive patients referred to the University of Alabama at
Birmingham Hypertension Clinic for uncontrolled hypertension were enrolled.
Refractory hypertension was defined as uncontrolled automated office BP >=135/85
mm Hg with the use of >=5 antihypertensive agents, including chlorthalidone and
spironolactone. Automated office BP measurements were based on 6 serial readings,
done automatically with the use of a BpTRU device unobserved in the clinic. Out
of-office BP measurements were done by 24-hour ambulatory BP monitor. Thirty-four
patients were diagnosed with refractory hypertension, of whom 31 had adequate
ambulatory BP monitor readings. White-coat effect was present in only 2 patients,
or 6.5% of the 31 patients with refractory hypertension, suggesting that white
coat effect is largely absent in patients with refractory hypertension. These
findings suggest that white-coat effect is not a common cause of apparent lack of
BP control in patients failing maximal antihypertensive treatment.
PMID- 28696224
TI - Increased Perfusion Pressure Drives Renal T-Cell Infiltration in the Dahl Salt
Sensitive Rat.
AB - Renal T-cell infiltration is a key component of salt-sensitive hypertension in
Dahl salt-sensitive (SS) rats. Here, we use an electronic servo-control technique
to determine the contribution of renal perfusion pressure to T-cell infiltration
in the SS rat kidney. An aortic balloon occluder placed around the aorta between
the renal arteries was used to maintain perfusion pressure to the left kidney at
control levels, ~128 mm Hg, during 7 days of salt-induced hypertension, whereas
the right kidney was exposed to increased renal perfusion pressure that averaged
157+/-4 mm Hg by day 7 of high-salt diet. The number of infiltrating T cells was
compared between the 2 kidneys. Renal T-cell infiltration was significantly
blunted in the left servo-controlled kidney compared with the right uncontrolled
kidney. The number of CD3+, CD3+CD4+, and CD3+CD8+ T cells were all significantly
lower in the left servo-controlled kidney. This effect was not specific to T
cells because CD45R+ (B cells) and CD11b/c+ (monocytes and macrophages) cell
infiltrations were all exacerbated in the hypertensive kidneys. Increased renal
perfusion pressure was also associated with augmented renal injury, with
increased protein casts and glomerular damage in the hypertensive kidney. Levels
of norepinephrine were comparable between the 2 kidneys, suggestive of equivalent
sympathetic innervation. Renal infiltration of T cells was not reversed by the
return of renal perfusion pressure to control levels after 7 days of salt
sensitive hypertension. We conclude that increased pressure contributes to the
initiation of renal T-cell infiltration during the progression of salt-sensitive
hypertension in SS rats.
PMID- 28696225
TI - Glypican-6 promotes the growth of developing long bones by stimulating Hedgehog
signaling.
AB - Autosomal-recessive omodysplasia (OMOD1) is a genetic condition characterized by
short stature, shortened limbs, and facial dysmorphism. OMOD1 is caused by loss
of-function mutations of glypican 6 (GPC6). In this study, we show that GPC6-null
embryos display most of the abnormalities found in OMOD1 patients and that
Hedgehog (Hh) signaling is significantly reduced in the long bones of these
embryos. The Hh-stimulatory activity of GPC6 was also observed in cultured cells,
where this GPC increased the binding of Hh to Patched 1 (Ptc1). Consistent with
this, GPC6 interacts with Hh through its core protein and with Ptc1 through its
glycosaminoglycan chains. Hh signaling is triggered at the primary cilium. In the
absence of Hh, we observed that GPC6 is localized outside of the cilium but moves
into the cilium upon the addition of Hh. We conclude that GPC6 stimulates Hh
signaling by binding to Hh and Ptc1 at the cilium and increasing the interaction
of the receptor and ligand.
PMID- 28696226
TI - Kaposi's sarcoma-associated herpesvirus stably clusters its genomes across
generations to maintain itself extrachromosomally.
AB - Genetic elements that replicate extrachromosomally are rare in mammals; however,
several human tumor viruses, including the papillomaviruses and the
gammaherpesviruses, maintain their plasmid genomes by tethering them to cellular
chromosomes. We have uncovered an unprecedented mechanism of viral replication:
Kaposi's sarcoma-associated herpesvirus (KSHV) stably clusters its genomes across
generations to maintain itself extrachromosomally. To identify and characterize
this mechanism, we developed two complementary, independent approaches: live-cell
imaging and a predictive computational model. The clustering of KSHV requires the
viral protein, LANA1, to bind viral genomes to nucleosomes arrayed on both
cellular and viral DNA. Clustering affects both viral partitioning and viral
genome numbers of KSHV. The clustering of KSHV plasmids provides it with an
effective evolutionary strategy to rapidly increase copy numbers of genomes per
cell at the expense of the total numbers of cells infected.
PMID- 28696227
TI - Translational regulation of viral secretory proteins by the 5' coding regions and
a viral RNA-binding protein.
AB - A primary function of 5' regions in many secretory protein mRNAs is to encode an
endoplasmic reticulum (ER) targeting sequence. In this study, we show how the
regions coding for the ER-targeting sequences of the influenza glycoproteins NA
and HA also function as translational regulatory elements that are controlled by
the viral RNA-binding protein (RBP) NS1. The translational increase depends on
the nucleotide composition and 5' positioning of the ER-targeting sequence coding
regions and is facilitated by the RNA-binding domain of NS1, which can associate
with ER membranes. Inserting the ER-targeting sequence coding region of NA into
different 5' UTRs confirmed that NS1 can promote the translation of secretory
protein mRNAs based on the nucleotides within this region rather than the
resulting amino acids. By analyzing human protein mRNA sequences, we found
evidence that this mechanism of using 5' coding regions and particular RBPs to
achieve gene-specific regulation may extend to human-secreted proteins.
PMID- 28696228
TI - Characterization of the Complete Nucleotide Sequences of IncA/C2 Plasmids
Carrying In809-Like Integrons from Enterobacteriaceae Isolates of Wildlife
Origin.
AB - A total of 18 Enterobacteriaceae (17 from gulls and 1 from a clinical sample)
collected from Australia, carrying IncA/C plasmids with the IMP-encoding In809
like integrons, were studied. Seven plasmids, being representatives of different
origins, plasmid sizes, replicon combinations, and resistance genes, were
completely sequenced. Plasmid pEc158, identified in a clinical Escherichia coli
ST752 isolate, showed extensive similarity to type 2 IncA/C2 plasmids. pEc158
carried none of the blaCMY-2-like region or ARI-B and ARI-A regions, while it
contained a hybrid transposon structure. The six remaining plasmids, which were
of wildlife origin, were highly similar to each other and probably were fusion
derivatives of type 1 and type 2 A/C2 plasmids. The latter plasmids contained an
ARI-B region and hybrid transposon structures. In all plasmids, hybrid transposon
structures containing In809-like integrons were inserted 3,434 bp downstream of
the rhs2 start codon. In all cases, the one outermost 38-bp inverted repeat (IR)
of the transposon was associated with the Tn1696 tnp module, while the other
outermost 38-bp IR of the transposon was associated with either a Tn6317-like
module or a Tn21 mer module. However, the internal structure of the transposon
and the resistance genes were different in each plasmid. These findings indicated
that, for the specific periods of time and settings, different IncA/C2 plasmid
types carrying In809-like elements circulated among isolates of wildlife and
clinical origins. Additionally, they provided the basis for speculations
regarding the reshuffling of IncA/C2 plasmids with In809-like integrons and
confirmed the rapid evolution of IncA/C2 plasmid lineages.
PMID- 28696229
TI - MDR1 and BCRP Transporter-Mediated Drug-Drug Interaction between Rilpivirine and
Abacavir and Effect on Intestinal Absorption.
AB - Rilpivirine (TMC278) is a highly potent nonnucleoside reverse transcriptase
inhibitor (NNRTI) representing an effective component of combination
antiretroviral therapy (cART) in the treatment of HIV-positive patients. Many
antiretroviral drugs commonly used in cART are substrates of ATP-binding cassette
(ABC) and/or solute carrier (SLC) drug transporters and, therefore, are prone to
pharmacokinetic drug-drug interactions (DDIs). The aim of our study was to
evaluate rilpivirine interactions with abacavir and lamivudine on selected ABC
and SLC transporters in vitro and assess its importance for pharmacokinetics in
vivo Using accumulation assays in MDCK cells overexpressing selected ABC or SLC
drug transporters, we revealed rilpivirine as a potent inhibitor of MDR1 and
BCRP, but not MRP2, OCT1, OCT2, or MATE1. Subsequent transport experiments across
monolayers of MDCKII-MDR1, MDCKII-BCRP, and Caco-2 cells demonstrated that
rilpivirine inhibits MDR1- and BCRP-mediated efflux of abacavir and increases its
transmembrane transport. In vivo experiments in male Wistar rats confirmed
inhibition of MDR1/BCRP in the small intestine, leading to a significant increase
in oral bioavailability of abacavir. In conclusion, rilpivirine inhibits MDR1 and
BCRP transporters and may affect pharmacokinetic behavior of concomitantly
administered substrates of these transporters, such as abacavir.
PMID- 28696230
TI - Implications of Antimicrobial Combinations in Complex Wound Biofilms Containing
Fungi.
AB - Diabetic foot ulcer treatment currently focuses on targeting bacterial biofilms,
while dismissing fungi. To investigate this, we used an in vitro biofilm model
containing bacteria and fungi, reflective of the wound environment, to test the
impact of antimicrobials. Here we showed that while monotreatment approaches
influenced biofilm composition, this had no discernible effect on overall
quantity. Only by combining bacterium- and fungus-specific antibiotics were we
able to decrease the biofilm bioburden, irrespective of composition.
PMID- 28696231
TI - Comparison of Plasma and Intrapulmonary Concentrations of Nafithromycin (WCK
4873) in Healthy Adult Subjects.
AB - The nafithromycin concentrations in the plasma, epithelial lining fluid (ELF),
and alveolar macrophages (AM) of 37 healthy adult subjects were measured
following repeated dosing of oral nafithromycin at 800 mg once daily for 3 days.
The values of noncompartmental pharmacokinetic (PK) parameters were determined
from serial plasma samples collected over a 24-h interval following the first and
third oral doses. Each subject underwent one standardized bronchoscopy with
bronchoalveolar lavage (BAL) at 3, 6, 9, 12, 24, or 48 h after the third dose of
nafithromycin. The mean +/- standard deviation values of the plasma PK parameters
after the first and third doses included maximum plasma concentrations (Cmax) of
1.02 +/- 0.31 MUg/ml and 1.39 +/- 0.36 MUg/ml, respectively; times to Cmax of
3.97 +/- 1.30 h and 3.69 +/- 1.28 h, respectively; clearances of 67.3 +/- 21.3
liters/h and 52.4 +/- 18.5 liters/h, respectively, and elimination half-lives of
7.7 +/- 1.1 h and 9.1 +/- 1.7 h, respectively. The values of the area under the
plasma concentration-time curve (AUC) from time zero to 24 h postdosing (AUC0-24)
for nafithromycin based on the mean or median total plasma concentrations at BAL
fluid sampling times were 16.2 MUg . h/ml. For ELF, the respective AUC0-24 values
based on the mean and median concentrations were 224.1 and 176.3 MUg . h/ml,
whereas for AM, the respective AUC0-24 values were 8,538 and 5,894 MUg . h/ml.
Penetration ratios based on ELF and total plasma AUC0-24 values based on the mean
and median concentrations were 13.8 and 10.9, respectively, whereas the ratios of
the AM to total plasma concentrations based on the mean and median concentrations
were 527 and 364, respectively. The sustained ELF and AM concentrations for 48 h
after the third dose suggest that nafithromycin has the potential to be a useful
agent for the treatment of lower respiratory tract infections. (This study has
been registered at ClinicalTrials.gov under registration no. NCT02453529.).
PMID- 28696232
TI - Community Composition Determines Activity of Antibiotics against Multispecies
Biofilms.
AB - In young cystic fibrosis (CF) patients, Staphylococcus aureus is typically the
most prevalent organism, while in adults, Pseudomonas aeruginosa is the major
pathogen. More recently, it was observed that also Streptococcus anginosus plays
an important role in exacerbations of respiratory symptoms. These species are
often coisolated from CF lungs, yet little is known about whether antibiotic
killing of one species is influenced by the presence of others. In the present
study, we compared the activities of various antibiotics against S. anginosus, S.
aureus, and P. aeruginosa when grown in monospecies biofilms with the activity
observed in a multispecies biofilm. Our results show that differences in
antibiotic activity against species grown in mono- and multispecies biofilms are
species and antibiotic dependent. Fewer S. anginosus cells are killed by
antibiotics that interfere with cell wall synthesis (amoxicillin plus sulbactam,
cefepime, imipenem, meropenem, and vancomycin) in the presence of S. aureus and
P. aeruginosa, while for ciprofloxacin, levofloxacin, and tobramycin, no
difference was observed. In addition, we observed that the cell-free supernatant
of S. aureus, but not that of P. aeruginosa biofilms, also caused this decrease
in killing. Overall, S. aureus was more affected by antibiotic treatment in a
multispecies biofilm, while for P. aeruginosa, no differences were observed
between growth in mono- or multispecies biofilms. The results of the present
study suggest that it is important to take the community composition into account
when evaluating the effect of antimicrobial treatments against certain species in
mixed biofilms.
PMID- 28696233
TI - Comparison of Omadacycline and Tigecycline Pharmacokinetics in the Plasma,
Epithelial Lining Fluid, and Alveolar Cells of Healthy Adult Subjects.
AB - The steady-state concentrations of omadacycline and tigecycline in the plasma,
epithelial lining fluid (ELF), and alveolar cells (AC) of 58 healthy adult
subjects were obtained. Subjects were administered either omadacycline at 100 mg
intravenously (i.v.) every 12 h for two doses followed by 100 mg i.v. every 24 h
for three doses or tigecycline at an initial dose of 100 mg i.v. followed by 50
mg i.v. every 12 h for six doses. A bronchoscopy and bronchoalveolar lavage were
performed once in each subject following the start of the fifth dose of
omadacycline at 0.5, 1, 2, 4, 8, 12, or 24 h and after the start of the seventh
dose of tigecycline at 2, 4, 6, or 12 h. The value of the area under the
concentration-time curve (AUC) from time zero to 24 h postdosing (AUC0-24) (based
on mean concentrations) in ELF and the ratio of the ELF to total plasma
omadacycline concentration based on AUC0-24 values were 17.23 mg . h/liter and
1.47, respectively. The AUC0-24 value in AC was 302.46 mg . h/liter, and the
ratio of the AC to total plasma omadacycline concentration was 25.8. In
comparison, the values of the AUC from time zero to 12 h postdosing (AUC0-12)
based on the mean concentrations of tigecycline in ELF and AC were 3.16 and 38.50
mg . h/liter, respectively. The ratio of the ELF and AC to total plasma
concentrations of tigecycline based on AUC0-12 values were 1.71 and 20.8,
respectively. The pharmacokinetic advantages of higher and sustained
concentrations of omadacycline compared to those of tigecycline in plasma, ELF,
and AC suggest that omadacycline is a promising antibacterial agent for the
treatment of lower respiratory tract bacterial infections caused by susceptible
pathogens.
PMID- 28696234
TI - Role of Daptomycin on Burn Wound Healing in an Animal Methicillin-Resistant
Staphylococcus aureus Infection Model.
AB - Prolonged hospitalization and antibiotic therapy are risk factors for the
development of methicillin-resistant Staphylococcus aureus (MRSA) infections in
thermal burn patients. We used a rat model to study the in vivo efficacy of
daptomycin in the treatment of burn wound infections by S. aureus, and we
evaluated the wound healing process through morphological and immunohistochemical
analysis. A copper bar heated in boiling water was applied on a paraspinal site
of each rat, resulting in two full-thickness burns. A small gauze was placed over
each burn and inoculated with 5 * 107 CFU of S. aureus ATCC 43300. The study
included two uninfected control groups with and without daptomycin treatment, an
infected control group that did not receive any treatment, and two infected
groups treated, respectively, with intraperitoneal daptomycin and teicoplanin.
The main outcome measures were quantitative culture, histological evaluation of
tissue repair, and immunohistochemical expression of wound healing markers:
epidermal growth factor receptor (EGFR) and fibroblast growth factor 2 (FGF-2).
The highest inhibition of infection was achieved in the group that received
daptomycin, which reduced the bacterial load from 107 CFU/ml to about 103 CFU/g
(P < 0.01). The groups treated with daptomycin showed better overall healing with
epithelialization and significantly higher collagen scores than the other groups,
and these findings were also confirmed by immunohistochemical data. In
conclusion, our results support the hypothesis that daptomycin is an important
modulator of wound repair by possibly reducing hypertrophic burn scar formation.
PMID- 28696235
TI - Evaluation of Combination Drug Therapy for Treatment of Antibiotic-Resistant
Inhalation Anthrax in a Murine Model.
AB - Bacillus anthracis is considered a likely agent to be used as a bioweapon, and
the use of a strain resistant to the first-line antimicrobial treatments is a
concern. We determined treatment efficacies against a ciprofloxacin-resistant
strain of B. anthracis (Cipr Ames) in a murine inhalational anthrax model. Ten
groups of 46 BALB/c mice were exposed by inhalation to 7 to 35 times the 50%
lethal dose (LD50) of B. anthracis Cipr Ames spores. Commencing at 36 h
postexposure, groups were administered intraperitoneal doses of sterile water for
injections (SWI) and ciprofloxacin alone (control groups), or ciprofloxacin
combined with two antimicrobials, including meropenem-linezolid, meropenem
clindamycin, meropenem-rifampin, meropenem-doxycycline, penicillin-linezolid,
penicillin-doxycycline, rifampin-linezolid, and rifampin-clindamycin, at
appropriate dosing intervals (6 or 12 h) for the respective antibiotics. Ten mice
per group were treated for 14 days and observed until day 28. The remaining
animals were euthanized every 6 to 12 h, and blood, lungs, and spleens were
collected for lethal factor (LF) and/or bacterial load determinations. All
combination groups showed significant survival over the SWI and ciprofloxacin
controls: meropenem-linezolid (P = 0.004), meropenem-clindamycin (P = 0.005),
meropenem-rifampin (P = 0.012), meropenem-doxycycline (P = 0.032), penicillin
doxycycline (P = 0.012), penicillin-linezolid (P = 0.026), rifampin-linezolid (P
= 0.001), and rifampin-clindamycin (P = 0.032). In controls, blood, lung, and
spleen bacterial counts increased to terminal endpoints. In combination treatment
groups, blood and spleen bacterial counts showed low/no colonies after 24-h
treatments. The LF fell below the detection limits for all combination groups yet
remained elevated in control groups. Combinations with linezolid had the greatest
inhibitory effect on mean LF levels.
PMID- 28696236
TI - Combination Therapy with Isavuconazole and Micafungin for Treatment of
Experimental Invasive Pulmonary Aspergillosis.
AB - Invasive pulmonary aspergillosis (IPA) is an important cause of morbidity and
mortality in immunocompromised patients. We hypothesized that simultaneous
inhibition of biosynthesis of ergosterol in the fungal cell membrane and (1->3)
beta-d-glucan in the cell wall, respectively, by the antifungal triazole
isavuconazole (ISA) and the echinocandin micafungin (MFG) may result in improved
outcomes in experimental IPA in persistently neutropenic rabbits. Treatments
included ISA at 20 mg/kg of body weight/day (ISA20), 40 mg/kg/day (ISA40), and 60
mg/kg/day (ISA60); MFG at 2 mg/kg/day (MFG2); combinations of ISA20 and MFG2,
ISA40 and MFG2, and ISA60 and MFG2; and no treatment (untreated controls [UC]).
The galactomannan index (GMI) and (1->3)-beta-d-glucan levels in serum were
measured. The residual fungal burden (number of CFU per gram) was significantly
reduced in ISA20-, ISA40-, ISA60-, ISA20-MFG2-, ISA40-MFG2-, and ISA60-MFG2
treated rabbits compared with that in MFG2-treated or UC rabbits (P < 0.01).
Measures of organism-mediated pulmonary injury, lung weights, and pulmonary
infarct score were lower in ISA40-MFG2-treated rabbits than in rabbits treated
with ISA40 or MFG2 alone (P < 0.01). Survival was prolonged in ISA40-MFG2-treated
rabbits in comparison to those treated with ISA40 or MFG2 alone (P < 0.01). These
outcome variables correlated directly with significant declines in GMI and serum
(1->3)-beta-d-glucan levels during therapy. The GMI correlated with measures of
organism-mediated pulmonary injury, lung weights (r = 0.764; P < 0.001), and
pulmonary infarct score (r = 0.911; P < 0.001). In summary, rabbits receiving
combination therapy with isavuconazole and micafungin demonstrated a significant
dose-dependent reduction in the residual fungal burden, decreased pulmonary
injury, prolonged survival, a lower GMI, and lower serum (1->3)-beta-d-glucan
levels in comparison to rabbits receiving isavuconazole or micafungin as a single
agent.
PMID- 28696237
TI - Persistent Loss of Hepatitis B Virus Markers in Serum without Cellular Immunity
by Combination of Peginterferon and Entecavir Therapy in Humanized Mice.
AB - Nucleot(s)ide analogues and peginterferon (PEG-IFN) treatment are the only
approved therapies for chronic hepatitis B virus (HBV) infection. However,
complete eradication of the virus, as indicated by persistent loss of hepatitis B
surface antigen (HBsAg), is rare among treated patients. This is due to long-term
persistence of the HBV genome in infected hepatocytes in the form of covalently
closed circular DNA (cccDNA). In this study, we investigated whether
administration of a large dose of a nucleoside analogue in combination with PEG
IFN can achieve long-term loss of HBsAg in human hepatocyte chimeric mice. Mice
were treated with a high dose of entecavir and/or PEG-IFN for 6 weeks. High-dose
combination therapy with both drugs resulted in persistently negative HBV DNA in
serum. Although small amounts of HBV DNA and cccDNA (0.1 and 0.01 copy/cell,
respectively) remained in the mouse livers, some of the mice remained
persistently negative for serum HBV DNA at 13 weeks after cessation of the
therapy. Serum HBsAg and hepatitis B core-related antigen (HBcrAg) continued to
decrease and eventually became negative at 12 weeks after cessation of the
therapy. Analysis of the HBV genome in treated mice showed accumulation of G-to-A
hypermutation and CpG III island methylation. Persistent loss of serum HBV DNA
and loss of HBV markers by high-dose entecavir and PEG-IFN combination treatment
in chimeric mice suggests that control of HBV can be achieved even in the absence
of a cellular immune response.
PMID- 28696238
TI - Sterilizing Effect of Ertapenem-Clavulanate in a Hollow-Fiber Model of
Tuberculosis and Implications on Clinical Dosing.
AB - Carbapenems are now being explored for treatment of multidrug-resistant
tuberculosis (MDR-TB), especially in conjunction with clavulanate. Clinical use
is constrained by the need for multiple parenteral doses per day and the lack of
knowledge of the optimal dose for sterilizing effect. Our objective was to
identify the ertapenem exposure associated with optimal sterilizing effect and
then design a once-a-day dose for clinical use. We utilized the hollow-fiber
system model of tuberculosis in a 28-day exposure-response study of 8 different
ertapenem doses in combination with clavulanate. The systems were sampled at
predetermined time points to verify the concentration-time profile and identify
the total bacterial burden. Inhibitory sigmoid maximum-effect (Emax) modeling was
used to identify the relationship between total bacterial burden and the drug
exposure and to identify optimal exposures. Contrary to the literature, ertapenem
clavulanate combination demonstrated good microbial kill and sterilizing effect.
In a dose fractionation hollow-fiber study, efficacy was linked to percentage of
the 24-h dosing interval of ertapenem concentration persisting above MIC (%TMIC).
We performed 10,000 MDR-TB patient computer-aided clinical trial simulations,
based on Monte Carlo methods, to identify the doses and schedule that would
achieve or exceed a %TMIC of >=40%. We identified an intravenous dosage of 2 g
once per day as achieving the target in 96% of patients. An ertapenem
susceptibility breakpoint MIC of 2 mg/liter was identified for that dose. An
ertapenem dosage of 2 g once daily is the most suitable to be tested in a phase
II study of sterilizing effect in MDR-TB patients.
PMID- 28696239
TI - Adverse Effects and Choice between the Injectable Agents Amikacin and Capreomycin
in Multidrug-Resistant Tuberculosis.
AB - The prolonged use of injectable agents in a regimen for the treatment of
multidrug-resistant tuberculosis (MDR-TB) is recommended by the World Health
Organization, despite its association with ototoxicity and nephrotoxicity. We
undertook this study to look at the relative adverse effects of capreomycin and
amikacin. We reviewed the case notes of 100 consecutive patients treated at four
MDR-TB treatment centers in the United Kingdom. The median total duration of
treatment with an injectable agent was 178 days (interquartile range [IQR], 109
to 192 days; n = 73) for those with MDR-TB, 179 days (IQR, 104 to 192 days; n =
12) for those with MDR-TB plus fluoroquinolone resistance, and 558 days (IQR, 324
to 735 days; n = 8) for those with extensively drug-resistant tuberculosis (XDR
TB). Injectable use was longer for those started with capreomycin (183 days; IQR,
123 to 197 days) than those started with amikacin (119 days; IQR, 83 to 177 days)
(P = 0.002). Excluding patients with XDR-TB, 51 of 85 (60%) patients were treated
with an injectable for over 6 months and 12 of 85 (14%) were treated with an
injectable for over 8 months. Forty percent of all patients discontinued the
injectable due to hearing loss. Fifty-five percent of patients experienced
ototoxicity, which was 5 times (hazard ratio [HR], 5.2; 95% confidence interval
[CI], 1.2 to 22.6; P = 0.03) more likely to occur in those started on amikacin
than in those treated with capreomycin only. Amikacin was associated with less
hypokalemia than capreomycin (odds ratio, 0.28; 95% CI, 0.11 to 0.72), with 5 of
37 (14%) patients stopping capreomycin due to recurrent electrolyte loss. There
was no difference in the number of patients experiencing a rise in the creatinine
level of >1.5 times the baseline level. Hearing loss is frequent in this cohort,
though its incidence is significantly lower in those starting capreomycin, which
should be given greater consideration as a first-line agent.
PMID- 28696240
TI - Biofilms Formed by Isolates from Recurrent Vulvovaginal Candidiasis Patients Are
Heterogeneous and Insensitive to Fluconazole.
AB - Vulvovaginal candidiasis (VVC) is a global health problem affecting ~75% of women
at least once in their lifetime. Here we examined the epidemiology of VVC in a
patient cohort to identify the causative organisms associated with VVC. Biofilm
forming capacity and antifungal sensitivity profiles were also assessed. We
report a shifting prevalence of Candida species with heterogeneous biofilm
forming capacity, which is associated with altered antifungal drug sensitivity.
PMID- 28696241
TI - Ethambutol Partitioning in Tuberculous Pulmonary Lesions Explains Its Clinical
Efficacy.
AB - Clinical trials and practice have shown that ethambutol is an important component
of the first-line tuberculosis (TB) regime. This contrasts the drug's rather
modest potency and lack of activity against nongrowing persister mycobacteria.
The standard plasma-based pharmacokinetic-pharmacodynamic profile of ethambutol
suggests that the drug may be of limited clinical value. Here, we hypothesized
that this apparent contradiction may be explained by favorable penetration of the
drug into TB lesions. First, we utilized novel in vitro lesion pharmacokinetic
assays and predicted good penetration of the drug into lesions. We then employed
mass spectrometry imaging and laser capture microdissection coupled to liquid
chromatography and tandem mass spectrometry (LCM and LC/MS-MS, respectively) to
show that ethambutol, indeed, accumulates in diseased tissues and penetrates the
major human-like lesion types represented in the rabbit model of TB disease with
a lesion-to-plasma exposure ratio ranging from 9 to 12. In addition, ethambutol
exhibits slow but sustained passive diffusion into caseum to reach concentrations
markedly higher than those measured in plasma at steady state. The results
explain why ethambutol has retained its place in the first-line regimen, validate
our in vitro lesion penetration assays, and demonstrate the critical importance
of effective lesion penetration for anti-TB drugs. Our findings suggest that in
vitro and in vivo lesion penetration evaluation should be included in TB drug
discovery programs. Finally, this is the first time that LCM with LC-MS/MS has
been used to quantify a small molecule at high spatial resolution in infected
tissues, a method that can easily be extended to other infectious diseases.
PMID- 28696242
TI - Pseudomonas aeruginosa Clinical Isolates in Nepal Coproducing Metallo-beta
Lactamases and 16S rRNA Methyltransferases.
AB - A total of 11 multidrug-resistant Pseudomonas aeruginosa clinical isolates were
obtained in Nepal. Four of these isolates harbored genes encoding one or more
carbapenemases (DIM-1, NDM-1, and/or VIM-2), and five harbored genes encoding a
16S rRNA methyltransferase (RmtB4 or RmtF2). A novel RmtF variant, RmtF2, had a
substitution (K65E) compared with the same gene in RmtF. To our knowledge, this
is the first report describing carbapenemase- and 16S rRNA methyltransferase
coproducing P. aeruginosa clinical isolates in Nepal.
PMID- 28696243
TI - Inhibiting 4EBP1 in Glioblastoma.
AB - Glioblastoma is the most common and aggressive adult brain cancer. Tumors show
frequent dysregulation of the PI3K-mTOR pathway. Although a number of small
molecules target the PI3K-AKT-mTOR axis, their preclinical and clinical efficacy
has been limited. Reasons for treatment failure include poor penetration of
agents into the brain and observations that blockade of PI3K or AKT minimally
affects downstream mTOR activity in glioma. Clinical trials using allosteric mTOR
inhibitors (rapamycin and rapalogs) to treat patients with glioblastoma have also
been unsuccessful or uncertain, in part, because rapamycin inefficiently blocks
the mTORC1 target 4EBP1 and feeds back to activate PI3K-AKT signaling. Inhibitors
of the mTOR kinase (TORKi) such as TAK-228/MLN0128 interact orthosterically with
the ATP- and substrate-binding pocket of mTOR kinase, efficiently block 4EBP1 in
vitro, and are currently being investigated in the clinical trials. Preclinical
studies suggest that TORKi have poor residence times of mTOR kinase, and our data
suggest that this poor pharmacology translates into disappointing efficacy in
glioblastoma xenografts. RapaLink-1, a TORKi linked to rapamycin, represents a
drug with improved pharmacology against 4EBP1. In this review, we clarify the
importance of 4EBP1 as a biomarker for the efficacy of PI3K-AKT-mTOR inhibitors
in glioblastoma. We also review mechanistic data by which RapaLink-1 blocks p
4EBP1 and discuss future clinical strategies for 4EBP1 inhibition in
glioblastoma. Clin Cancer Res; 24(1); 14-21. (c)2017 AACR.
PMID- 28696244
TI - Effect of vitrification on in vitro development and imprinted gene Grb10 in mouse
embryos.
AB - Vitrification of embryos is a routine procedure in IVF (in vitro fertilization)
laboratories. In the present study, we aimed to investigate the effect of
vitrification on mouse preimplantation embryo development in vitro, and effect on
the epigenetic status of imprinted gene Grb10 in mouse embryos. The blastocyst
formation rate for vitrified 8-cell embryos was similar to the non-vitrified 8
cell embryos, whereas the blastocyst hatching rate was lower than that of the non
vitrified group. The expression level of Grb10 major-type transcript decreased
significantly in vitrified blastocysts compared with non-vitrified and in vivo
blastocysts. Moreover, the global DNA methylation level in 8-cell embryos and
blastocysts, and the DNA methylation at CpG island 1 (CGI1) of Grb10 in
blastocysts were also significantly decreased after vitrification. In vitro
culture condition had no adverse effect, except for on the DNA methylation in
Grb10 CGI1. These results suggest that vitrification may reduce the in vitro
development of mouse 8-cell embryos and affect the expression and DNA methylation
of imprinted gene Grb10.
PMID- 28696245
TI - The histone codes for meiosis.
AB - Meiosis is a specialized process that produces haploid gametes from diploid cells
by a single round of DNA replication followed by two successive cell divisions.
It contains many special events, such as programmed DNA double-strand break (DSB)
formation, homologous recombination, crossover formation and resolution. These
events are associated with dynamically regulated chromosomal structures, the
dynamic transcriptional regulation and chromatin remodeling are mainly modulated
by histone modifications, termed 'histone codes'. The purpose of this review is
to summarize the histone codes that are required for meiosis during
spermatogenesis and oogenesis, involving meiosis resumption, meiotic asymmetric
division and other cellular processes. We not only systematically review the
functional roles of histone codes in meiosis but also discuss future trends and
perspectives in this field.
PMID- 28696246
TI - Farnesoid X Receptor Agonism Protects against Diabetic Tubulopathy: Potential Add
On Therapy for Diabetic Nephropathy.
AB - Established therapies for diabetic nephropathy (dNP) delay but do not prevent its
progression. The shortage of established therapies may reflect the inability to
target the tubular compartment. The chemical chaperone tauroursodeoxycholic acid
(TUDCA) ameliorates maladaptive endoplasmic reticulum (ER) stress signaling and
experimental dNP. Additionally, TUDCA activates the farnesoid X receptor (FXR),
which is highly expressed in tubular cells. We hypothesized that TUDCA
ameliorates maladaptive ER signaling via FXR agonism specifically in tubular
cells. Indeed, TUDCA induced expression of FXR-dependent genes (SOCS3 and DDAH1)
in tubular cells but not in other renal cells. In vivo, TUDCA reduced glomerular
and tubular injury in db/db and diabetic endothelial nitric oxide synthase
deficient mice. FXR inhibition with Z-guggulsterone or vivo-morpholino targeting
of FXR diminished the ER-stabilizing and renoprotective effects of TUDCA.
Notably, these in vivo approaches abolished tubular but not glomerular protection
by TUDCA. Combined intervention with TUDCA and the angiotensin-converting enzyme
inhibitor enalapril in 16-week-old db/db mice reduced albuminuria more
efficiently than did either treatment alone. Although both therapies reduced
glomerular damage, only TUDCA ameliorated tubular damage. Thus, interventions
that specifically protect the tubular compartment in dNP, such as FXR agonism,
may provide renoprotective effects on top of those achieved by inhibiting
angiotensin-converting enzyme.
PMID- 28696247
TI - MicroRNA-92a Mediates Endothelial Dysfunction in CKD.
AB - CKD is an independent risk factor for cardiovascular disease (CVD). The
accumulation of uremic toxins in CKD induces oxidative stress and endothelial
dysfunction. MicroRNA-92a (miR-92a) is induced by oxidative stress in endothelial
cells (ECs) and involved in angiogenesis and atherosclerosis. We investigated a
role for oxidative stress-responsive miR-92a in CKD. Our study of patients at
three clinical sites showed increased serum miR-92a level with decreased kidney
function. In cultured ECs, human CKD serum or uremic toxins (such as indoxyl
sulfate), compared with non-CKD serum, induced the levels of miR-92a and
suppressed the expression of miR-92a targets, including key endothelial
protective molecules. The antioxidant N-acetylcysteine inhibited these
vasculopathic properties. In rats, adenine-induced CKD associated with increased
levels of miR-92a in aortas, serum, and CD144+ endothelial microparticles.
Furthermore, CD144+ microparticles from human uremic serum contained more miR-92a
than those from control serum. Additional analysis showed a positive correlation
between serum levels of miR-92a and indoxyl sulfate in a cohort of patients with
ESRD undergoing hemodialysis. Collectively, our findings suggest that the uremic
toxins accumulated in CKD can upregulate miR-92a in ECs, which impairs EC
function and predisposes patients to CVD.
PMID- 28696248
TI - Intracellular APOL1 Risk Variants Cause Cytotoxicity Accompanied by Energy
Depletion.
AB - Population genetic approaches have uncovered a strong association between kidney
diseases and two sequence variants of the APOL1 gene, called APOL1 risk variant
G1 and variant G2, compared with the nonrisk G0 allele. However, the mechanism
whereby these variants lead to disease manifestation and, in particular, whether
this involves an intracellular or extracellular pool of APOL1 remains unclear.
Herein, we show a predominantly intracellular localization of APOL1 G0 and the
renal risk variants, which localized to membranes of the endoplasmic reticulum in
podocyte cell lines. This localization did not depend on the N-terminal signal
peptide that mediates APOL1 secretion into the circulation. Additionally, a
fraction of these proteins localized to structures surrounding mitochondria. In
vitro overexpression of G1 or G2 lacking the signal peptide inhibited cell
viability, triggered phosphorylation of stress-induced kinases, increased the
phosphorylation of AMP-activated protein kinase, reduced intracellular potassium
levels, and reduced mitochondrial respiration rates. These findings indicate that
functions at intracellular membranes, specifically those of the endoplasmic
reticulum and mitochondria, are crucial factors in APOL1 renal risk variant
mediated cell injury.
PMID- 28696249
TI - Haploinsufficiency of the Transcription Factor Ets-1 Is Renoprotective in Dahl
Salt-Sensitive Rats.
AB - Studies using Dahl salt-sensitive (SS) rats identified specific quantitative
trait loci that predispose animals to hypertension-associated albuminuria and
kidney injury. We explored the hypothesis that kidney-specific expression of the
transcription factor Ets-1, located within one of these loci on chromosome 8,
mediates glomerular injury in SS hypertension. During the first week on a high
salt diet, SS rats and SS rats with only one functioning Ets-1 gene (ES rats)
demonstrated similar increases in BP. However, serum creatinine concentration,
albuminuria, and glomerular expression of ETS-1 and two ETS-1 targets, MCP-1 and
MMP2, did not increase as substantially in ES rats as in SS rats. Mean BP
subsequently increased further in SS rats and remained higher than that of ES
rats for the rest of the study. After 4 weeks of high-salt intake, ES rats still
showed a lower mean serum creatinine concentration and less albuminuria, as well
as less histologic evidence of glomerular injury and kidney fibrosis, than SS
rats did. To investigate the specific contribution of renal Ets-1, we
transplanted kidneys from ES or SS rats into salt-resistant SS-Chr 13BN/McwiCrl
(SS-13BN) rats. Within 10 days on a high-salt diet, BP increased similarly in ES
and SS allograft recipients, becoming significantly higher than the BP of control
isograft recipients. However, mean serum creatinine concentration and albuminuria
remained lower in ES allograft recipients than in SS allograft recipients at 2
weeks, and ES allografts showed less glomerular injury and interstitial fibrosis.
In conclusion, reduced renal expression of ETS-1 prevented hypertension
associated kidney injury in SS rats.
PMID- 28696250
TI - American Heart Association's Call to Action for Payment and Delivery System
Reform.
AB - The healthcare system is undergoing a transition from paying for volume to paying
for value. Clinicians, as well as public and private payers, are beginning to
implement alternative delivery and payment models, such as the patient-centered
medical home, accountable care organizations, and bundled payment arrangements.
Implementation of these new models will necessitate delivery system
transformation and will actively involve all fields of medical care, in
particular medicine and surgery. This call to action, on behalf of the American
Heart Association's Expert Panel on Payment and Delivery System Reform, serves to
offer support and direction for further involvement by the American Heart
Association. In doing so, it (1) provides baseline review and definition of the
present models and some of the early results of these delivery models, including
outcomes; (2) initiates a conversation within the American Heart Association on
the impact of payment and delivery system reform, as well as how the American
Heart Association should engage in the interest of patients; (3) issues a call to
action to our organization and to cardiovascular and stroke health professionals
across the country to become educated about these models so to as to understand
their impact on patient care; and (4) asks the government and other funding
agencies, including the American Heart Association, to begin supporting and
prioritizing meaningful research endeavors to further evaluate these models.
PMID- 28696251
TI - Endothelin-1 Stimulates Vasoconstriction Through Rab11A Serine 177
Phosphorylation.
AB - RATIONALE: Large-conductance calcium-activated potassium channels (BK) are
composed of pore-forming BKalpha and auxiliary beta1 subunits in arterial smooth
muscle cells (myocytes). Vasoconstrictors, including endothelin-1 (ET-1), inhibit
myocyte BK channels, leading to contraction, but mechanisms involved are unclear.
Recent evidence indicates that BKalpha is primarily plasma membrane localized,
whereas the cellular location of beta1 can be rapidly altered by Rab11A-positive
recycling endosomes. Whether vasoconstrictors regulate the multisubunit
composition of surface BK channels to stimulate contraction is unclear.
OBJECTIVE: Test the hypothesis that ET-1 inhibits BK channels by altering BKalpha
and beta1 surface trafficking in myocytes, identify mechanisms involved, and
determine functional significance in myocytes of small cerebral arteries. METHODS
AND RESULTS: ET-1, through activation of PKC (protein kinase C), reduced surface
beta1 abundance and the proximity of beta1 to surface BKalpha in myocytes. In
contrast, ET-1 did not alter surface BKalpha, total beta1, or total BKalpha
proteins. ET-1 stimulated Rab11A phosphorylation, which reduced Rab11A activity.
Rab11A serine 177 was identified as a high-probability PKC phosphorylation site.
Expression of a phosphorylation-incapable Rab11A construct (Rab11A S177A) blocked
the ET-1-induced Rab11A phosphorylation, reduction in Rab11A activity, and
decrease in surface beta1 protein. ET-1 inhibited single BK channels and
transient BK currents in myocytes and stimulated vasoconstriction via a PKC
dependent mechanism that required Rab11A S177. In contrast, NO-induced Rab11A
activation, surface trafficking of beta1 subunits, BK channel and transient BK
current activation, and vasodilation did not involve Rab11A S177. CONCLUSIONS: ET
1 stimulates PKC-mediated phosphorylation of Rab11A at serine 177, which inhibits
Rab11A and Rab11A-dependent surface trafficking of beta1 subunits. The decrease
in surface beta1 subunits leads to a reduction in BK channel calcium-sensitivity,
inhibition of transient BK currents, and vasoconstriction. We describe a unique
mechanism by which a vasoconstrictor inhibits BK channels and identify Rab11A
serine 177 as a modulator of arterial contractility.
PMID- 28696252
TI - Thermoneutrality but Not UCP1 Deficiency Suppresses Monocyte Mobilization Into
Blood.
AB - RATIONALE: Ambient temperature is a risk factor for cardiovascular disease. Cold
weather increases cardiovascular events, but paradoxically, cold exposure is
metabolically protective because of UCP1 (uncoupling protein 1)-dependent
thermogenesis. OBJECTIVE: We sought to determine the differential effects of
ambient environmental temperature challenge and UCP1 activation in relation to
cardiovascular disease progression. METHODS AND RESULTS: Using mouse models of
atherosclerosis housed at 3 different ambient temperatures, we observed that cold
temperature enhanced, whereas thermoneutral housing temperature inhibited
atherosclerotic plaque growth, as did deficiency in UCP1. However, whereas UCP1
deficiency promoted poor glucose tolerance, thermoneutral housing enhanced
glucose tolerance, and this effect held even in the context of UCP1 deficiency.
In conditions of thermoneutrality, but not UCP1 deficiency, circulating monocyte
counts were reduced, likely accounting for fewer monocytes entering plaques.
Reductions in circulating blood monocytes were also found in a large human cohort
in correlation with environmental temperature. By contrast, reduced plaque growth
in mice lacking UCP1 was linked to lower cholesterol. Through application of a
positron emission tomographic tracer to track CCR2+ cell localization and
intravital 2-photon imaging of bone marrow, we associated thermoneutrality with
an increased monocyte retention in bone marrow. Pharmacological activation of
beta3-adrenergic receptors applied to mice housed at thermoneutrality induced
UCP1 in beige fat pads but failed to promote monocyte egress from the marrow.
CONCLUSIONS: Warm ambient temperature is, like UCP1 deficiency, atheroprotective,
but the mechanisms of action differ. Thermoneutrality associates with reduced
monocyte egress from the bone marrow in a UCP1-dependent manner in mice and
likewise may also suppress blood monocyte counts in man.
PMID- 28696253
TI - The Ox40/Ox40 Ligand Pathway Promotes Pathogenic Th Cell Responses, Plasmablast
Accumulation, and Lupus Nephritis in NZB/W F1 Mice.
AB - Ox40 ligand (Ox40L) locus genetic variants are associated with the risk for
systemic lupus erythematosus (SLE); however, it is unclear how Ox40L contributes
to SLE pathogenesis. In this study, we evaluated the contribution of Ox40L and
its cognate receptor, Ox40, using in vivo agonist and antagonist approaches in
the NZB * NZW (NZB/W) F1 mouse model of SLE. Ox40 was highly expressed on several
CD4 Th cell subsets in the spleen and kidney of diseased mice, and expression
correlated with disease severity. Treatment of aged NZB/W F1 mice with agonist
anti-Ox40 mAbs potently exacerbated renal disease, which was accompanied by
activation of kidney-infiltrating T cells and cytokine production. The agonist
mAbs also induced activation and inflammatory gene expression in splenic CD4 T
cells, including IFN-regulated genes, increased the number of follicular helper T
cells and plasmablasts in the spleen, and led to elevated levels of serum IgM and
enhanced renal glomerular IgM deposition. In a type I IFN-accelerated lupus
model, treatment with an antagonist Ox40:Fc fusion protein significantly delayed
the onset of severe proteinuria and improved survival. These data support the
hypothesis that the Ox40/Ox40L pathway drives cellular and humoral autoimmune
responses during lupus nephritis in NZB/W F1 mice and emphasize the potential
clinical value of targeting this pathway in human lupus.
PMID- 28696254
TI - Human Monocyte Subsets Are Transcriptionally and Functionally Altered in Aging in
Response to Pattern Recognition Receptor Agonists.
AB - Age-related alterations in immunity have been linked to increased incidence of
infections and decreased responses to vaccines in the aging population. Human
peripheral blood monocytes are known to promote Ag presentation and antiviral
activities; however, the impact of aging on monocyte functions remains an open
question. We present an in-depth global analysis examining the impact of aging on
classical (CD14+CD16-), intermediate (CD14+CD16+), and nonclassical
(CD14dimCD16+) monocytes. Monocytes sorted from nonfrail healthy adults (21-40 y)
and old (>=65 y) individuals were analyzed after stimulation with TLR4, TLR7/8,
and retinoic acid-inducible gene I agonists. Our data showed that under
nonstimulated conditions, monocyte subsets did not reveal significant age-related
alternations; however, agonist stimulated-monocytes from adults and old subjects
did show differences at the transcriptional and functional levels. These
alternations in many immune-related transcripts and biological processes resulted
in reduced production of IFN-alpha, IFN-gamma, IL-1beta, CCL20, and CCL8, and
higher expression of CX3CR1 in monocytes from old subjects. Our findings
represent a comprehensive analysis of the influence of human aging on pattern
recognition receptors signaling and monocyte functions, and have implications for
strategies to enhance the immune response in the context of infection and
immunization.
PMID- 28696255
TI - Regulated Polarization of Tumor-Associated Macrophages by miR-145 via Colorectal
Cancer-Derived Extracellular Vesicles.
AB - Macrophages are polarized into functional classically activated and alternatively
activated (M2) phenotypes depending on their microenvironment, and these cells
play an important role in the immune system. M2-like polarization of tumor
associated macrophages (TAMs) is activated by various secretions from cancer
cells; however, the interaction between cancer cells and TAMs is not well
understood. Recent studies showed that cancer cell-derived extracellular vesicles
(EVs) contribute to tumor development and modulation of the tumor
microenvironment. In the current study, we investigated colorectal cancer-derived
EVs containing miR-145 with respect to the polarization of TAMs. Colorectal
cancer cells positively secreted miR-145 via EVs, which were taken up by
macrophage-like cells. Interestingly, colorectal cancer-derived EVs polarized
macrophage-like cells into the M2-like phenotype through the downregulation of
histone deacetylase 11 An in vivo study showed that EV-treated macrophages caused
significant enlargement of the tumor volumes. These findings suggest that
colorectal cancer cells use miR-145 within EVs to efficiently modulate M2-like
macrophage polarization and tumor progression.
PMID- 28696256
TI - A Novel Subset of Anti-Inflammatory CD138+ Macrophages Is Deficient in Mice with
Experimental Lupus.
AB - Dead cells accumulating in the tissues may contribute to chronic inflammation. We
examined the cause of impaired apoptotic cell clearance in human and murine
lupus. Dead cells accumulated in bone marrow from lupus patients but not from
nonautoimmune patients undergoing myeloablation, where they were efficiently
removed by macrophages (MPhi). Impaired apoptotic cell uptake by MPhi also was
seen in mice treated i.p. with pristane (develop lupus) but not mineral oil (MO)
(do not develop lupus). The inflammatory response to both pristane and MO rapidly
depleted resident (Tim4+) large peritoneal MPhi. The peritoneal exudate of
pristane-treated mice contained mainly Ly6Chi inflammatory monocytes; whereas in
MO-treated mice, it consisted predominantly of a novel subset of highly
phagocytic MPhi resembling small peritoneal MPhi (SPM) that expressed CD138+ and
the scavenger receptor Marco. Treatment with anti-Marco-neutralizing Abs and the
class A scavenger receptor antagonist polyinosinic acid inhibited phagocytosis of
apoptotic cells by CD138+ MPhi. CD138+ MPhi expressed IL-10R, CD206, and CCR2 but
little TNF-alpha or CX3CR1. They also expressed high levels of activated CREB, a
transcription factor implicated in generating alternatively activated MPhi.
Similar cells were identified in the spleen and lung of MO-treated mice and also
were induced by LPS. We conclude that highly phagocytic, CD138+ SPM-like cells
with an anti-inflammatory phenotype may promote the resolution of inflammation in
lupus and infectious diseases. These SPM-like cells are not restricted to the
peritoneum and may help clear apoptotic cells from tissues such as the lung,
helping to prevent chronic inflammation.
PMID- 28696257
TI - Transient and dynamic DNA supercoiling potently stimulates the leu-500 promoter
in Escherichia coli.
AB - The inactive prokaryotic leu-500 promoter (Pleu-500) contains a single A-to-G
point mutation in the -10 region of the leucine operon promoter, which causes
leucine auxotrophy. This promoter can be activated by (-) DNA supercoiling in
Escherichia coli topA strains. However, whether this activation arises from
global, permanent, or transient, dynamic supercoiling is still not fully
understood. In this article, using a newly established in vivo system carrying a
pair of divergently coupled promoters, i.e. an IPTG-inducible promoter and Pleu
500 that control the expression of lacZ and luc (the firefly luciferase gene),
respectively, we demonstrate that transient, dynamic (-) DNA supercoiling
provided by divergent transcription in both wild-type and topA strains can
potently activate Pleu-500 We found that this activation depended on the promoter
strength and the length of RNA transcripts, which are functional characteristics
of transcription-coupled DNA supercoiling (TCDS) precisely predicted by the twin
supercoiled domain model of transcription in which a (+) supercoiled domain is
produced ahead of the RNA polymerase and a (-) supercoiled domain behind it. We
also demonstrate that TCDS can be generated on topologically open DNA molecules,
i.e. linear DNA molecules, in Escherichia coli, suggesting that topological
boundaries or barriers are not required for the production of TCDS in vivo This
work demonstrates that transient, dynamic TCDS by RNA polymerases is a major
chromosome remodeling force in E. coli and greatly influences the nearby, coupled
promoters/transcription.
PMID- 28696258
TI - Effects of DNA end configuration on XRCC4-DNA ligase IV and its stimulation of
Artemis activity.
AB - In humans, nonhomologous DNA end-joining (NHEJ) is the major pathway by which DNA
double-strand breaks are repaired. Recognition of each broken DNA end by the DNA
repair protein Ku is the first step in NHEJ, followed by the iterative binding of
nucleases, DNA polymerases, and the XRCC4-DNA ligase IV (X4-LIV) complex in an
order influenced by the configuration of the two DNA ends at the break site. The
endonuclease Artemis improves joining efficiency by functioning in a complex with
DNA-dependent protein kinase, catalytic subunit (DNA-PKcs) that carries out
endonucleolytic cleavage of 5' and 3' overhangs. Previously, we observed that X4
LIV alone can stimulate Artemis activity on 3' overhangs, but this DNA-PKcs
independent endonuclease activity of Artemis awaited confirmation. Here, using in
vitro nuclease and ligation assays, we find that stimulation of Artemis nuclease
activity by X4-LIV and the efficiency of blunt-end ligation are determined by
structural configurations at the DNA end. Specifically, X4-LIV stimulated Artemis
to cut near the end of 3' overhangs without the involvement of other NHEJ
proteins. Of note, this ligase complex is not able to stimulate Artemis activity
at hairpins or at 5' overhangs. We also found that X4-LIV and DNA-PKcs interfere
with one another with respect to stimulating Artemis activity at 3' overhangs,
favoring the view that these NHEJ proteins are sequentially rather than
concurrently recruited to DNA ends. These data suggest specific functional and
positional relationships among these components that explain genetic and
molecular features of NHEJ and V(D)J recombination within cells.
PMID- 28696259
TI - Interplay between the phosphatase PHLPP1 and E3 ligase RNF41 stimulates proper
kinetochore assembly via the outer-kinetochore protein SGT1.
AB - Kinetochores link chromosomes to spindle microtubules and are essential for
accurate chromosome segregation during cell division. Kinetochores assemble at
the centromeric region of chromosomes as a multiprotein complex. However, the
molecular mechanisms of kinetochore assembly have not yet been fully elucidated.
In this study, we identified pleckstrin homology domain and leucine-rich repeat
protein phosphatase 1 (PHLPP1) as a regulatory phosphatase that facilitates
proper kinetochore assembly. We found that PHLPP1 interacted with the essential
outer-kinetochore protein SGT1 and stabilized its protein levels. Loss of PHLPP1
from cells led to SGT1 degradation and thereby caused defective kinetochore
assembly. We also found that the ring finger protein 41 (RNF41) as an E3 ligase
ubiquitinated and degraded SGT1 in a phosphorylation-dependent manner. PHLPP1
dephosphorylated SGT1 at four conserved residues (Ser-17, Ser-249, Ser-289, and
Thr-233) and thereby prevented SGT1 from associating with RNF41, in turn,
countering SGT1 degradation. Importantly, depletion of RNF41 or expression of a
non-phosphorylatable SGT1 mutant rescued the kinetochore defects caused by the
loss of PHLPP1. Taken together, our results suggest that PHLPP1 plays an
important role in the assembly of kinetochores by counteracting RNF41-mediated
SGT1 degradation.
PMID- 28696260
TI - Biophysical analysis of Arabidopsis protein-only RNase P alone and in complex
with tRNA provides a refined model of tRNA binding.
AB - RNase P is a universal enzyme that removes 5' leader sequences from tRNA
precursors. The enzyme is therefore essential for maturation of functional tRNAs
and mRNA translation. RNase P represents a unique example of an enzyme that can
occur either as ribonucleoprotein or as protein alone. The latter form of the
enzyme, called protein-only RNase P (PRORP), is widespread in eukaryotes in which
it can provide organellar or nuclear RNase P activities. Here, we have focused on
Arabidopsis nuclear PRORP2 and its interaction with tRNA substrates. Affinity
measurements helped assess the respective importance of individual
pentatricopeptide repeat motifs in PRORP2 for RNA binding. We characterized the
PRORP2 structure by X-ray crystallography and by small-angle X-ray scattering in
solution as well as that of its complex with a tRNA precursor by small-angle X
ray scattering. Of note, our study reports the first structural data of a PRORP
tRNA complex. Combined with complementary biochemical and biophysical analyses,
our structural data suggest that PRORP2 undergoes conformational changes to
accommodate its substrate. In particular, the catalytic domain and the RNA
binding domain can move around a central hinge. Altogether, this work provides a
refined model of the PRORP-tRNA complex that illustrates how protein-only RNase P
enzymes specifically bind tRNA and highlights the contribution of protein
dynamics to achieve this specific interaction.
PMID- 28696261
TI - Complex interplay of kinetic factors governs the synergistic properties of HIV-1
entry inhibitors.
AB - The homotrimeric HIV-1 envelope glycoprotein (Env) undergoes receptor-triggered
structural changes that mediate viral entry through membrane fusion. This process
is inhibited by chemokine receptor antagonists (CoRAs) that block Env-receptor
interactions and by fusion inhibitors (FIs) that disrupt Env conformational
transitions. Synergy between CoRAs and FIs has been attributed to a CoRA
dependent decrease in the rate of viral membrane fusion that extends the lifetime
of the intermediate state targeted by FIs. Here, we demonstrated that the
magnitude of CoRA/FI synergy unexpectedly depends on FI-binding affinity and the
stoichiometry of chemokine receptor binding to trimeric Env. For C-peptide FIs
(clinically represented by enfuvirtide), synergy waned as binding strength
decreased until inhibitor combinations behaved additively. Curiously, this
affinity dependence on synergy was absent for 5-Helix-type FIs. We linked this
complex behavior to the CoRA dependence of Env deactivation following FI binding.
For both FI classes, reducing chemokine receptor levels on target cells or
eliminating competent chemokine receptor-binding sites on Env trimers resulted in
a loss of synergistic activity. These data imply that the stoichiometry required
for CoRA/FI synergy exceeds that required for HIV-1 entry. Our analysis suggests
two distinct roles for chemokine receptor binding, one to trigger formation of
the FI-sensitive intermediate state and another to facilitate subsequent
conformational transitions. Together, our results could explain the wide variety
of previously reported activities for CoRA/FI combinations. These findings also
have implications for the combined use of CoRAs and FIs in antiviral therapies
and point to a multifaceted role for chemokine receptor binding in promoting HIV
1 entry.
PMID- 28696263
TI - An Unintended Consequence of the 21st-Century Cures Act for Patients With Heart
Failure.
PMID- 28696264
TI - Coronary Artery Calcification Among Endurance Athletes: "Hearts of Stone".
PMID- 28696262
TI - Human serine racemase structure/activity relationship studies provide mechanistic
insight and point to position 84 as a hot spot for beta-elimination function.
AB - There is currently great interest in human serine racemase, the enzyme
responsible for producing the NMDA co-agonist d-serine. Reported correlation of d
serine levels with disorders including Alzheimer's disease, ALS, and ischemic
brain damage (elevated d-serine) and schizophrenia (reduced d-serine) has further
piqued this interest. Reported here is a structure/activity relationship study of
position Ser84, the putative re-face base. In the most extreme case of functional
reprogramming, the S84D mutant displays a dramatic reversal of beta-elimination
substrate specificity in favor of l-serine over the normally preferred l-serine-O
sulfate (~1200-fold change in kcat/Km ratios) and l (l-THA; ~5000-fold change in
kcat/Km ratios) alternative substrates. On the other hand, the S84T (which
performs l-Ser racemization activity), S84A (good kcat but high Km for l-THA
elimination), and S84N mutants (nearly WT efficiency for l-Ser elimination)
displayed intermediate activity, all showing a preference for the anionic
substrates, but generally attenuated compared with the native enzyme. Inhibition
studies with l-erythro-beta-hydroxyaspartate follow this trend, with both WT
serine racemase and the S84N mutant being competitively inhibited, with Ki = 31
+/- 1.5 MUm and 1.5 +/- 0.1 mm, respectively, and the S84D being inert to
inhibition. Computational modeling pointed to a key role for residue Arg-135 in
binding and properly positioning the l-THA and l-serine-O-sulfate substrates and
the l-erythro-beta-hydroxyaspartate inhibitor. Examination of available sequence
data suggests that Arg-135 may have originated for l-THA-like beta-elimination
function in earlier evolutionary variants, and examination of available
structural data suggests that a Ser84-H2O-Lys114 hydrogen-bonding network in
human serine racemase lowers the pKa of the Ser84re-face base.
PMID- 28696266
TI - Thirty-Day Readmissions for Critical Limb Ischemia: Ready for a New Quality
Metric?
PMID- 28696265
TI - Black-White Differences in Incident Fatal, Nonfatal, and Total Coronary Heart
Disease.
AB - BACKGROUND: Blacks have higher coronary heart disease (CHD) mortality compared
with whites. However, a previous study suggests that nonfatal CHD risk may be
lower for black versus white men. METHODS: We compared fatal and nonfatal CHD
incidence and CHD case-fatality among blacks and whites in the Atherosclerosis
Risk in Communities study (ARIC), the Cardiovascular Health Study (CHS), and the
Reasons for Geographic and Racial Differences in Stroke study (REGARDS) by sex.
Participants 45 to 64 years of age in ARIC (men=6479, women=8488) and REGARDS
(men=5296, women=7822), and >=65 years of age in CHS (men=1836, women=2790) and
REGARDS (men=3381, women=4112), all without a history of CHD, were analyzed.
Fatal and nonfatal CHD incidence was assessed from baseline (ARIC=1987-1989,
CHS=1989-1990, REGARDS=2003-2007) through up to 11 years of follow-up. RESULTS:
Age-adjusted hazard ratios comparing black versus white men 45 to 64 years of age
in ARIC and REGARDS were 2.09 (95% confidence interval, 1.42-3.06) and 2.11 (1.32
3.38), respectively, for fatal CHD, and 0.82 (0.64-1.05) and 0.94 (0.69-1.28),
respectively, for nonfatal CHD. After adjustment for social determinants of
health and cardiovascular risk factors, hazard ratios in ARIC and REGARDS were
1.19 (95% confidence interval, 0.74-1.92) and 1.09 (0.62-1.93), respectively, for
fatal CHD, and 0.64 (0.47-0.86) and 0.67 (0.48-0.95), respectively, for nonfatal
CHD. Similar patterns were present among men >=65 years of age in CHS and
REGARDS. Among women 45 to 64 years of age in ARIC and REGARDS, age-adjusted
hazard ratios comparing blacks versus whites were 2.61 (95% confidence interval,
1.57-4.34) and 1.79 (1.06-3.03), respectively, for fatal CHD, and 1.47 (1.13
1.91) and 1.29 (0.91-1.83), respectively, for nonfatal CHD. After multivariable
adjustment, hazard ratios in ARIC and REGARDS were 0.67 (95% confidence interval,
0.36-1.24) and 1.00 (0.54-1.85), respectively, for fatal CHD, and 0.70 (0.51
0.97) and 0.70 (0.46-1.06), respectively, for nonfatal CHD. Racial differences in
CHD incidence were attenuated among older women. CHD case fatality was higher
among black versus white men and women, and the difference remained similar after
multivariable adjustment. CONCLUSIONS: After accounting for social determinants
of health and risk factors, black men and women have similar risk for fatal CHD
compared with white men and women, respectively. However, the risk for nonfatal
CHD is consistently lower for black versus white men and women.
PMID- 28696267
TI - Eye-Opening Potential for Tetraspanin Tspan12 as a Therapeutic Target for
Diseases of the Retinal Vasculature.
PMID- 28696269
TI - Emerging Data Show E-Cigarettes May Pose Heart Risk.
PMID- 28696270
TI - Looking for the Right Side in Large Vessel Vasculitis: A Multimodality Imaging
Guided Success.
PMID- 28696268
TI - Personalizing Risk Stratification for Sudden Death in Dilated Cardiomyopathy: The
Past, Present, and Future.
AB - Results from the DANISH Study (Danish Study to Assess the Efficacy of ICDs in
Patients With Non-Ischemic Systolic Heat Failure on Mortality) suggest that for
many patients with dilated cardiomyopathy (DCM), implantable cardioverter
defibrillators do not increase longevity. Accurate identification of patients who
are more likely to die of an arrhythmia and less likely to die of other causes is
required to ensure improvement in outcomes and wise use of resources. Until now,
left ventricular ejection fraction has been used as a key criterion for selecting
patients with DCM for an implantable cardioverter-defibrillator for primary
prevention purposes. However, registry data suggest that many patients with DCM
and an out-of-hospital cardiac arrest do not have a markedly reduced left
ventricular ejection fraction. In addition, many patients with reduced left
ventricular ejection fraction die of nonsudden causes of death. Methods to
predict a higher or lower risk of sudden death include the detection of
myocardial fibrosis (a substrate for ventricular arrhythmia), microvolt T-wave
alternans (a marker of electrophysiological vulnerability), and genetic testing.
Midwall fibrosis is identified by late gadolinium enhancement cardiovascular
magnetic resonance imaging in ~30% of patients and provides incremental value in
addition to left ventricular ejection fraction for the prediction of sudden
cardiac death events. Microvolt T-wave alternans represents another promising
predictor, supported by large meta-analyses that have highlighted the negative
predictive value of this test. However, neither of these strategies have been
routinely adopted for risk stratification in clinical practice. More convincing
data from randomized trials are required to inform the management of patients
with these features. Understanding of the genetics of DCM and how specific
mutations affect arrhythmic risk is also rapidly increasing. The finding of a
mutation in lamin A/C, the cause of ~6% of idiopathic DCM, commonly underpins
more aggressive management because of the malignant nature of the associated
phenotype. With the expansion of genetic sequencing, the identification of
further high-risk mutations appears likely, leading to better-informed clinical
decision making and providing insight into disease mechanisms. Over the next 5 to
10 years, we expect these techniques to be integrated into the existing algorithm
to form a more sensitive, specific, and cost-effective approach to the selection
of patients with DCM for implantable cardioverter-defibrillator implantation.
PMID- 28696271
TI - Letter by Zimmermann et al Regarding Article, "Excess Cardiovascular Risk in
Women Relative to Men Referred for Coronary Angiography Is Associated With
Severely Impaired Coronary Flow Reserve, Not Obstructive Disease".
PMID- 28696272
TI - Response by Taqueti and Di Carli to Letter Regarding Article, "Excess
Cardiovascular Risk in Women Relative to Men Referred for Coronary Angiography Is
Associated With Severely Impaired Coronary Flow Reserve, Not Obstructive
Disease".
PMID- 28696273
TI - Letter by Stergiopoulos et al Regarding Article, "Burden of Arrhythmia in
Pregnancy".
PMID- 28696274
TI - Response by Vaidya et al to Letter Regarding Article, "Burden of Arrhythmia in
Pregnancy".
PMID- 28696275
TI - A Lectin Receptor-Like Kinase Mediates Pattern-Triggered Salicylic Acid
Signaling.
AB - Plant surface-localized pathogen recognition receptors (PRRs) perceive conserved
microbial features, termed pathogen-associated molecular patterns (PAMPs),
resulting in disease resistance. PAMP perception leads to calcium influx, MAPK
activation, a burst of reactive oxygen species (ROS) mediated by RbohD,
accumulation of the defense hormone salicylic acid (SA), and callose deposition.
Lectin receptor-like kinases (LecRKs) belong to a specific PRR family and are
important players in plant innate immunity. Here, we report that LecRK-IX.2 is a
positive regulator of PRR-triggered immunity. Pathogen infection activated the
transcription of Arabidopsis (Arabidopsis thaliana) LecRK-IX.2, and the LecRK
IX.2 knockout lines exhibited enhanced susceptibility to virulent Pseudomonas
syringae pv tomato DC3000. In addition, LecRK-IX.2 is capable of inducing RbohD
phosphorylation, likely by recruiting calcium-dependent protein kinases to
trigger ROS production in Arabidopsis. Overexpression of LecRK-IX.2 resulted in
elevated ROS and SA and enhanced systemic acquired resistance to P. syringae pv
tomato DC3000. Our data highlight the importance of LecRKs in plant immune
signaling and SA accumulation.
PMID- 28696276
TI - Progress in Our Understanding of Wzx Flippase for Translocation of Bacterial
Membrane Lipid-Linked Oligosaccharide.
AB - Translocation of lipid-linked oligosaccharides is a common theme across
prokaryotes and eukaryotes. For bacteria, such activity is used in cell wall
construction, polysaccharide synthesis, and the relatively recently discovered
protein glycosylation. To the best of our knowledge, the Gram-negative inner
membrane flippase Wzx was the first protein identified as being involved in
oligosaccharide translocation, and yet we still have only a limited understanding
of this protein after 3 decades of research. At present, Wzx is known to be a
multitransmembrane protein with enormous sequence diversity that flips
oligosaccharide substrates with varied degrees of preference. In this review, we
provide an overview of the major findings for this protein, with a particular
focus on substrate preference.
PMID- 28696277
TI - Learning from Adversity?
AB - Many two-component regulatory systems, including Escherichia coli PhoRB, are
positively autoregulated, so stimuli result in an increase in the concentration
of signaling proteins. When the quantity of signaling proteins depends on
exposure history, how do past conditions affect future responses to stimuli?
Hoffer et al. (J. Bacteriol. 183:4914-4917, 2001,
https://doi.org/doi:10.1128/JB.183.16.4914-4917.2001) previously reported that E.
coli bacteria "learn" from phosphate starvation and respond more rapidly to
subsequent episodes of starvation. Gao et al. (J. Bacteriol. 199:e00390-17, 2017,
https://doi.org/doi:10.1128/JB.00390-17) describe another aspect of hysteresis in
the PhoRB regulon. Phosphate starvation also leads to a global decline in
transcription, counteracting the effects of positive autoregulation and resulting
in a similar net pho response (homeostasis), regardless of exposure history.
PMID- 28696278
TI - Outer Membrane Permeability of Cyanobacterium Synechocystis sp. Strain PCC 6803:
Studies of Passive Diffusion of Small Organic Nutrients Reveal the Absence of
Classical Porins and Intrinsically Low Permeability.
AB - The outer membrane of heterotrophic Gram-negative bacteria plays the role of a
selective permeability barrier that prevents the influx of toxic compounds while
allowing the nonspecific passage of small hydrophilic nutrients through porin
channels. Compared with heterotrophic Gram-negative bacteria, the outer membrane
properties of cyanobacteria, which are Gram-negative photoautotrophs, are not
clearly understood. In this study, using small carbohydrates, amino acids, and
inorganic ions as permeation probes, we determined the outer membrane
permeability of Synechocystis sp. strain PCC 6803 in intact cells and in
proteoliposomes reconstituted with outer membrane proteins. The permeability of
this cyanobacterium was >20-fold lower than that of Escherichia coli The
predominant outer membrane proteins Slr1841, Slr1908, and Slr0042 were not
permeable to organic nutrients and allowed only the passage of inorganic ions.
Only the less abundant outer membrane protein Slr1270, a homolog of the E. coli
export channel TolC, was permeable to organic solutes. The activity of Slr1270 as
a channel was verified in a recombinant Slr1270-producing E. coli outer membrane.
The lack of putative porins and the low outer membrane permeability appear to
suit the cyanobacterial autotrophic lifestyle; the highly impermeable outer
membrane would be advantageous to cellular survival by protecting the cell from
toxic compounds, especially when the cellular physiology is not dependent on the
uptake of organic nutrients.IMPORTANCE Because the outer membrane of Gram
negative bacteria affects the flux rates for various substances into and out of
the cell, its permeability is closely associated with cellular physiology. The
outer membrane properties of cyanobacteria, which are photoautotrophic Gram
negative bacteria, are not clearly understood. Here, we examined the outer
membrane of Synechocystis sp. strain PCC 6803. We revealed that it is relatively
permeable to inorganic ions but is markedly less permeable to organic nutrients,
with >20-fold lower permeability than the outer membrane of Escherichia coli Such
permeability appears to fit the cyanobacterial lifestyle, in which the diffusion
pathway for inorganic solutes may suffice to sustain the autotrophic physiology,
illustrating a link between outer membrane permeability and the cellular
lifestyle.
PMID- 28696279
TI - Defining the Functionally Important Domain and Amino Acid Residues in
Mycobacterium tuberculosis Integration Host Factor for Genome Stability, DNA
Binding, and Integrative Recombination.
AB - The integration host factor of Mycobacterium tuberculosis (mIHF) consists of a
single polypeptide chain, the product of the ihf gene. We previously revealed
that mIHF is a novel member of a new class of nucleoid-associated proteins that
have important roles in DNA damage response, nucleoid compaction, and integrative
recombination. The mIHF contains a region of 86 amino acids at its N terminus,
absent from both alpha- and beta-subunits of Escherichia coli IHF. However, the
functional significance of an extra 86-amino-acid region in the full-length
protein remains unknown. Here, we report the structure/function relationship of
the DNA-binding and integrative recombination-stimulating activity of mIHF.
Deletion mutagenesis showed that an extra 86-amino-acid region at the N terminus
is dispensable; the C-terminal region possesses the sequences essential for its
known biological functions, including the ability to suppress the sensitivity of
E. coli DeltaihfA and DeltaihfB cells to DNA-damaging agents, DNA binding, DNA
multimerization-circularization, and stimulation of phage L5 integrase-catalyzed
integrative recombination. Single and double alanine substitutions at positions
Arg170 and Arg171, located at the mIHF DNA-binding site, abrogated its capacity
to suppress the sensitivity of E. coli DeltaihfA and DeltaihfB cells to DNA
damaging agents. The variants encoded by these mutant alleles failed to bind DNA
and stimulate integrative recombination. Interestingly, the DNA-binding activity
of the mIHF-R173A variant remained largely unaffected; however, it was unable to
stimulate integrative recombination, thus revealing a separation-of-function
allele of mIHF. The functional and structural characterization of this separation
of-function allele of mIHF could reveal previously unknown functions of
IHF.IMPORTANCE The integration host factor of Mycobacterium tuberculosis is a
novel nucleoid-associated protein. mIHF plays a vital role in DNA damage
response, nucleoid compaction, and integrative recombination. Intriguingly, mIHF
contains an extra 86-amino-acid region at its N terminus, absent from both alpha-
and beta-subunits of Escherichia coli IHF, whose functional significance is
unknown. Furthermore, a triad of arginine residues located at the mIHF-DNA
interface have been implicated in a range of its functions. Here, we reveal the
roles of N- and C-terminal regions of mIHF and the individual residues in the Arg
triad for their ability to provide protection in vivo against DNA damage, bind
DNA, and stimulate integrase-catalyzed site-specific recombination.
PMID- 28696280
TI - Nontypeable Haemophilus influenzae releases DNA and DNABII proteins via a T4SS
like complex and ComE of the type IV pilus machinery.
AB - Biofilms formed by nontypeable Haemophilus influenzae (NTHI) are central to the
chronicity, recurrence, and resistance to treatment of multiple human respiratory
tract diseases including otitis media, chronic rhinosinusitis, and exacerbations
of both cystic fibrosis and chronic obstructive pulmonary disease. Extracellular
DNA (eDNA) and associated DNABII proteins are essential to the overall
architecture and structural integrity of biofilms formed by NTHI and all other
bacterial pathogens tested to date. Although cell lysis and outer-membrane
vesicle extrusion are possible means by which these canonically intracellular
components might be released into the extracellular environment for incorporation
into the biofilm matrix, we hypothesized that NTHI additionally used a mechanism
of active DNA release. Herein, we describe a mechanism whereby DNA and associated
DNABII proteins transit from the bacterial cytoplasm to the periplasm via an
inner-membrane pore complex (TraC and TraG) with homology to type IV secretion
like systems. These components exit the bacterial cell through the ComE pore
through which the NTHI type IV pilus is expressed. The described mechanism is
independent of explosive cell lysis or cell death, and the release of DNA is
confined to a discrete subpolar location, which suggests a novel form of DNA
release from viable NTHI. Identification of the mechanisms and determination of
the kinetics by which critical biofilm matrix-stabilizing components are released
will aid in the design of novel biofilm-targeted therapeutic and preventative
strategies for diseases caused by NTHI and many other human pathogens known to
integrate eDNA and DNABII proteins into their biofilm matrix.
PMID- 28696281
TI - Synaptic properties of the lemniscal and paralemniscal pathways to the mouse
somatosensory thalamus.
AB - Somatosensory information is thought to arrive in thalamus through two
glutamatergic routes called the lemniscal and paralemniscal pathways via the
ventral posterior medial (VPm) and posterior medial (POm) nuclei. Here we
challenge the view that these pathways functionally represent parallel
information routes. Using electrical stimulation and an optogenetic approach in
brain slices from the mouse, we investigated the synaptic properties of the
lemniscal and paralemniscal input to VPm and POm. Stimulation of the lemniscal
pathway produced class 1, or "driver," responses in VPm relay cells, which is
consistent with this being an information-bearing channel. However, stimulation
of the paralemniscal pathway produced two distinct types of responses in POm
relay cells: class 1 (driver) responses in 29% of the cells, and class 2, or
"modulator," responses in the rest. Our data suggest that, unlike the lemniscal
pathway, the paralemniscal one is not homogenous and that it is primarily
modulatory. This finding requires major rethinking regarding the routes of
somatosensory information to cortex and suggests that the paralemniscal route is
chiefly involved in modulatory functions rather than simply being an information
route parallel to the lemniscal channel.
PMID- 28696282
TI - Accurate age estimation in small-scale societies.
AB - Precise estimation of age is essential in evolutionary anthropology, especially
to infer population age structures and understand the evolution of human life
history diversity. However, in small-scale societies, such as hunter-gatherer
populations, time is often not referred to in calendar years, and accurate age
estimation remains a challenge. We address this issue by proposing a Bayesian
approach that accounts for age uncertainty inherent to fieldwork data. We
developed a Gibbs sampling Markov chain Monte Carlo algorithm that produces
posterior distributions of ages for each individual, based on a ranking order of
individuals from youngest to oldest and age ranges for each individual. We first
validate our method on 65 Agta foragers from the Philippines with known ages, and
show that our method generates age estimations that are superior to previously
published regression-based approaches. We then use data on 587 Agta collected
during recent fieldwork to demonstrate how multiple partial age ranks coming from
multiple camps of hunter-gatherers can be integrated. Finally, we exemplify how
the distributions generated by our method can be used to estimate important
demographic parameters in small-scale societies: here, age-specific fertility
patterns. Our flexible Bayesian approach will be especially useful to improve
cross-cultural life history datasets for small-scale societies for which reliable
age records are difficult to acquire.
PMID- 28696283
TI - Suboptimal T-cell receptor signaling compromises protein translation, ribosome
biogenesis, and proliferation of mouse CD8 T cells.
AB - Global transcriptomic and proteomic analyses of T cells have been rich sources of
unbiased data for understanding T-cell activation. Lack of full concordance of
these datasets has illustrated that important facets of T-cell activation are
controlled at the level of translation. We undertook translatome analysis of CD8
T-cell activation, combining polysome profiling and microarray analysis. We
revealed that altering T-cell receptor stimulation influenced recruitment of
mRNAs to heavy polysomes and translation of subsets of genes. A major pathway
that was compromised, when TCR signaling was suboptimal, was linked to ribosome
biogenesis, a rate-limiting factor in both cell growth and proliferation.
Defective TCR signaling affected transcription and processing of ribosomal RNA
precursors, as well as the translation of specific ribosomal proteins and
translation factors. Mechanistically, IL-2 production was compromised in weakly
stimulated T cells, affecting the abundance of Myc protein, a known regulator of
ribosome biogenesis. Consequently, weakly activated T cells showed impaired
production of ribosomes and a failure to maintain proliferative capacity after
stimulation. We demonstrate that primary T cells respond to various environmental
cues by regulating ribosome biogenesis and mRNA translation at multiple levels to
sustain proliferation and differentiation.
PMID- 28696284
TI - Caffeine induces gastric acid secretion via bitter taste signaling in gastric
parietal cells.
AB - Caffeine, generally known as a stimulant of gastric acid secretion (GAS), is a
bitter-tasting compound that activates several taste type 2 bitter receptors
(TAS2Rs). TAS2Rs are expressed in the mouth and in several extraoral sites, e.g.,
in the gastrointestinal tract, in which their functional role still needs to be
clarified. We hypothesized that caffeine evokes effects on GAS by activation of
oral and gastric TAS2Rs and demonstrate that caffeine, when administered
encapsulated, stimulates GAS, whereas oral administration of a caffeine solution
delays GAS in healthy human subjects. Correlation analysis of data obtained from
ingestion of the caffeine solution revealed an association between the magnitude
of the GAS response and the perceived bitterness, suggesting a functional role of
oral TAS2Rs in GAS. Expression of TAS2Rs, including cognate TAS2Rs for caffeine,
was shown in human gastric epithelial cells of the corpus/fundus and in HGT-1
cells, a model for the study of GAS. In HGT-1 cells, various bitter compounds as
well as caffeine stimulated proton secretion, whereby the caffeine-evoked effect
was (i) shown to depend on one of its cognate receptor, TAS2R43, and adenylyl
cyclase; and (ii) reduced by homoeriodictyol (HED), a known inhibitor of
caffeine's bitter taste. This inhibitory effect of HED on caffeine-induced GAS
was verified in healthy human subjects. These findings (i) demonstrate that
bitter taste receptors in the stomach and the oral cavity are involved in the
regulation of GAS and (ii) suggest that bitter tastants and bitter-masking
compounds could be potentially useful therapeutics to regulate gastric pH.
PMID- 28696285
TI - Early Paleocene landbird supports rapid phylogenetic and morphological
diversification of crown birds after the K-Pg mass extinction.
AB - Evidence is accumulating for a rapid diversification of birds following the K-Pg
extinction. Recent molecular divergence dating studies suggest that birds
radiated explosively during the first few million years of the Paleocene;
however, fossils from this interval remain poorly represented, hindering our
understanding of morphological and ecological specialization in early neoavian
birds. Here we report a small fossil bird from the Nacimiento Formation of New
Mexico, constrained to 62.221-62.517 Ma. This partial skeleton represents the
oldest arboreal crown group bird known. Phylogenetic analyses recovered
Tsidiiyazhi abini gen. et sp. nov. as a member of the Sandcoleidae, an extinct
basal clade of stem mousebirds (Coliiformes). The discovery of Tsidiiyazhi pushes
the minimum divergence ages of as many as nine additional major neoavian lineages
into the earliest Paleocene, compressing the duration of the proposed explosive
post-K-Pg radiation of modern birds into a very narrow temporal window parallel
to that suggested for placental mammals. Simultaneously, Tsidiiyazhi provides
evidence for the rapid morphological (and likely ecological) diversification of
crown birds. Features of the foot indicate semizygodactyly (the ability to
facultatively reverse the fourth pedal digit), and the arcuate arrangement of the
pedal trochleae bears a striking resemblance to the conformation in owls
(Strigiformes). Inclusion of fossil taxa and branch length estimates impacts
ancestral state reconstructions, revealing support for the independent evolution
of semizygodactyly in Coliiformes, Leptosomiformes, and Strigiformes, none of
which is closely related to extant clades exhibiting full zygodactyly.
PMID- 28696286
TI - Intranasal oxytocin treatment for social deficits and biomarkers of response in
children with autism.
AB - Autism spectrum disorder (ASD) is characterized by core social deficits.
Prognosis is poor, in part, because existing medications target only associated
ASD features. Emerging evidence suggests that the neuropeptide oxytocin (OXT) may
be a blood-based biomarker of social functioning and a possible treatment for
ASD. However, prior OXT treatment trials have produced equivocal results, perhaps
because of variability in patients' underlying neuropeptide biology, but this
hypothesis has not been tested. Using a double-blind, randomized, placebo
controlled, parallel design, we tested the efficacy and tolerability of 4-wk
intranasal OXT treatment (24 International Units, twice daily) in 32 children
with ASD, aged 6-12 y. When pretreatment neuropeptide measures were included in
the statistical model, OXT compared with placebo treatment significantly enhanced
social abilities in children with ASD [as measured by the trial's primary outcome
measure, the Social Responsiveness Scale (SRS)]. Importantly, pretreatment blood
OXT concentrations also predicted treatment response, such that individuals with
the lowest pretreatment OXT concentrations showed the greatest social
improvement. OXT was well tolerated, and its effects were specific to social
functioning, with no observed decrease in repetitive behaviors or anxiety.
Finally, as with many trials, some placebo-treated participants showed
improvement on the SRS. This enhanced social functioning was mirrored by a
posttreatment increase in their blood OXT concentrations, suggesting that
increased endogenous OXT secretion may underlie this improvement. These findings
indicate that OXT treatment enhances social abilities in children with ASD and
that individuals with pretreatment OXT signaling deficits may stand to benefit
the most from OXT treatment.
PMID- 28696287
TI - Genomic architecture of biomass heterosis in Arabidopsis.
AB - Heterosis is most frequently manifested by the substantially increased vigorous
growth of hybrids compared with their parents. Investigating genomic variations
in natural populations is essential to understand the initial molecular
mechanisms underlying heterosis in plants. Here, we characterized the genomic
architecture associated with biomass heterosis in 200 Arabidopsis hybrids. The
genome-wide heterozygosity of hybrids makes a limited contribution to biomass
heterosis, and no locus shows an obvious overdominance effect in hybrids.
However, the accumulation of significant genetic loci identified in genome-wide
association studies (GWAS) in hybrids strongly correlates with better-parent
heterosis (BPH). Candidate genes for biomass BPH fall into diverse biological
functions, including cellular, metabolic, and developmental processes and
stimulus-responsive pathways. Important heterosis candidates include WUSCHEL,
ARGOS, and some genes that encode key factors involved in cell cycle regulation.
Interestingly, transcriptomic analyses in representative Arabidopsis hybrid
combinations reveal that heterosis candidate genes are functionally enriched in
stimulus-responsive pathways, including responses to biotic and abiotic stimuli
and immune responses. In addition, stimulus-responsive genes are repressed to low
parent levels in hybrids with high BPH, whereas middle-parent expression patterns
are exhibited in hybrids with no BPH. Our study reveals a genomic architecture
for understanding the molecular mechanisms of biomass heterosis in Arabidopsis,
in which the accumulation of the superior alleles of genes involved in metabolic
and cellular processes improve the development and growth of hybrids, whereas the
overall repressed expression of stimulus-responsive genes prioritizes growth over
responding to environmental stimuli in hybrids under normal conditions.
PMID- 28696288
TI - Inhibition of the integrated stress response reverses cognitive deficits after
traumatic brain injury.
AB - Traumatic brain injury (TBI) is a leading cause of long-term neurological
disability, yet the mechanisms underlying the chronic cognitive deficits
associated with TBI remain unknown. Consequently, there are no effective
treatments for patients suffering from the long-lasting symptoms of TBI. Here, we
show that TBI persistently activates the integrated stress response (ISR), a
universal intracellular signaling pathway that responds to a variety of cellular
conditions and regulates protein translation via phosphorylation of the
translation initiation factor eIF2alpha. Treatment with ISRIB, a potent drug-like
small-molecule inhibitor of the ISR, reversed the hippocampal-dependent cognitive
deficits induced by TBI in two different injury mouse models-focal contusion and
diffuse concussive injury. Surprisingly, ISRIB corrected TBI-induced memory
deficits when administered weeks after the initial injury and maintained
cognitive improvement after treatment was terminated. At the physiological level,
TBI suppressed long-term potentiation in the hippocampus, which was fully
restored with ISRIB treatment. Our results indicate that ISR inhibition at time
points late after injury can reverse memory deficits associated with TBI. As
such, pharmacological inhibition of the ISR emerges as a promising avenue to
combat head trauma-induced chronic cognitive deficits.
PMID- 28696289
TI - Correction for Kang et al., Identification and characterization of high methane
emitting abandoned oil and gas wells.
PMID- 28696290
TI - Correction for Bahari-Javan et al., HDAC1 links early life stress to
schizophrenia-like phenotypes.
PMID- 28696291
TI - On the debris-level origins of adhesive wear.
AB - Every contacting surface inevitably experiences wear. Predicting the exact amount
of material loss due to wear relies on empirical data and cannot be obtained from
any physical model. Here, we analyze and quantify wear at the most fundamental
level, i.e., wear debris particles. Our simulations show that the asperity
junction size dictates the debris volume, revealing the origins of the long
standing hypothesized correlation between the wear volume and the real contact
area. No correlation, however, is found between the debris volume and the normal
applied force at the debris level. Alternatively, we show that the junction size
controls the tangential force and sliding distance such that their product, i.e.,
the tangential work, is always proportional to the debris volume, with a
proportionality constant of 1 over the junction shear strength. This study
provides an estimation of the debris volume without any empirical factor,
resulting in a wear coefficient of unity at the debris level. Discrepant
microscopic and macroscopic wear observations and models are then contextualized
on the basis of this understanding. This finding offers a way to characterize the
wear volume in atomistic simulations and atomic force microscope wear
experiments. It also provides a fundamental basis for predicting the wear
coefficient for sliding rough contacts, given the statistics of junction clusters
sizes.
PMID- 28696292
TI - Acute inflammation regulates neuroregeneration through the NF-kappaB pathway in
olfactory epithelium.
AB - Adult neural stem cells/progenitor cells residing in the basal layer of the
olfactory epithelium are capable of reconstituting the neuroepithelium even after
severe damage. The molecular events underlying this regenerative capacity remain
elusive. Here we show that the repair of neuroepithelium after lesioning is
accompanied by an acute, but self-limited, inflammatory process. Attenuation of
inflammatory cell recruitment and cytokine production by dexamethasone impairs
proliferation of progenitor horizontal basal cells (HBCs) and subsequent neuronal
differentiation. Using TNF-alpha receptor-deficient mice, we identify TNF-alpha
signaling as an important contributor to this inflammatory and reparative
process, mainly through TNF-alpha receptor 1. HBC-selective genetic ablation of
RelA (p65), the transcriptional activator of the NF-kappaB pathway, retards
inflammation and impedes proliferation at the early stages of regeneration and
suggests HBCs directly participate in cross-talk between immune response and
neurogenesis. Loss of RelA in the regenerating neuroepithelium perturbs the
homeostasis between proliferation and apoptosis while enhancing JNK signaling.
Together, our results support a model in which acute inflammation after injury
initiates important regenerative signals in part through NF-kappaB-mediated
signaling that activates neural stem cells to reconstitute the olfactory
epithelium.
PMID- 28696293
TI - Bayesian markets to elicit private information.
AB - Financial markets reveal what investors think about the future, and prediction
markets are used to forecast election results. Could markets also encourage
people to reveal private information, such as subjective judgments (e.g., "Are
you satisfied with your life?") or unverifiable facts? This paper shows how to
design such markets, called Bayesian markets. People trade an asset whose value
represents the proportion of affirmative answers to a question. Their trading
position then reveals their own answer to the question. The results of this paper
are based on a Bayesian setup in which people use their private information
(their "type") as a signal. Hence, beliefs about others' types are correlated
with one's own type. Bayesian markets transform this correlation into a mechanism
that rewards truth telling. These markets avoid two complications of alternative
methods: they need no knowledge of prior information and no elicitation of
metabeliefs regarding others' signals.
PMID- 28696294
TI - TRPM7 senses oxidative stress to release Zn2+ from unique intracellular vesicles.
AB - TRPM7 (transient receptor potential cation channel subfamily M member 7)
regulates gene expression and stress-induced cytotoxicity and is required in
early embryogenesis through organ development. Here, we show that the majority of
TRPM7 is localized in abundant intracellular vesicles. These vesicles (M7Vs) are
distinct from endosomes, lysosomes, and other familiar vesicles or organelles.
M7Vs accumulate Zn2+ in a glutathione-enriched, reduced lumen when cytosolic Zn2+
concentrations are elevated. Treatments that increase reactive oxygen species
(ROS) trigger TRPM7-dependent Zn2+ release from the vesicles, whereas reduced
glutathione prevents TRPM7-dependent cytosolic Zn2+ influx. These observations
strongly support the notion that ROS-mediated TRPM7 activation releases Zn2+ from
intracellular vesicles after Zn2+ overload. Like the endoplasmic reticulum, these
vesicles are a distributed system for divalent cation uptake and release, but in
this case the primary divalent ion is Zn2+ rather than Ca2.
PMID- 28696295
TI - Biological annihilation via the ongoing sixth mass extinction signaled by
vertebrate population losses and declines.
AB - The population extinction pulse we describe here shows, from a quantitative
viewpoint, that Earth's sixth mass extinction is more severe than perceived when
looking exclusively at species extinctions. Therefore, humanity needs to address
anthropogenic population extirpation and decimation immediately. That conclusion
is based on analyses of the numbers and degrees of range contraction (indicative
of population shrinkage and/or population extinctions according to the
International Union for Conservation of Nature) using a sample of 27,600
vertebrate species, and on a more detailed analysis documenting the population
extinctions between 1900 and 2015 in 177 mammal species. We find that the rate of
population loss in terrestrial vertebrates is extremely high-even in "species of
low concern." In our sample, comprising nearly half of known vertebrate species,
32% (8,851/27,600) are decreasing; that is, they have decreased in population
size and range. In the 177 mammals for which we have detailed data, all have lost
30% or more of their geographic ranges and more than 40% of the species have
experienced severe population declines (>80% range shrinkage). Our data indicate
that beyond global species extinctions Earth is experiencing a huge episode of
population declines and extirpations, which will have negative cascading
consequences on ecosystem functioning and services vital to sustaining
civilization. We describe this as a "biological annihilation" to highlight the
current magnitude of Earth's ongoing sixth major extinction event.
PMID- 28696296
TI - Multiplexed RNAi therapy against brain tumor-initiating cells via lipopolymeric
nanoparticle infusion delays glioblastoma progression.
AB - Brain tumor-initiating cells (BTICs) have been identified as key contributors to
therapy resistance, recurrence, and progression of diffuse gliomas, particularly
glioblastoma (GBM). BTICs are elusive therapeutic targets that reside across the
blood-brain barrier, underscoring the urgent need to develop novel therapeutic
strategies. Additionally, intratumoral heterogeneity and adaptations to
therapeutic pressure by BTICs impede the discovery of effective anti-BTIC
therapies and limit the efficacy of individual gene targeting. Recent discoveries
in the genetic and epigenetic determinants of BTIC tumorigenesis offer novel
opportunities for RNAi-mediated targeting of BTICs. Here we show that BTIC growth
arrest in vitro and in vivo is accomplished via concurrent siRNA knockdown of
four transcription factors (SOX2, OLIG2, SALL2, and POU3F2) that drive the
proneural BTIC phenotype delivered by multiplexed siRNA encapsulation in the
lipopolymeric nanoparticle 7C1. Importantly, we demonstrate that 7C1 nano
encapsulation of multiplexed RNAi is a viable BTIC-targeting strategy when
delivered directly in vivo in an established mouse brain tumor. Therapeutic
potential was most evident via a convection-enhanced delivery method, which shows
significant extension of median survival in two patient-derived BTIC xenograft
mouse models of GBM. Our study suggests that there is potential advantage in
multiplexed targeting strategies for BTICs and establishes a flexible nonviral
gene therapy platform with the capacity to channel multiplexed RNAi schemes to
address the challenges posed by tumor heterogeneity.
PMID- 28696297
TI - mTORC1 activates SREBP-2 by suppressing cholesterol trafficking to lysosomes in
mammalian cells.
AB - mTORC1 is known to activate sterol regulatory element-binding proteins (SREBPs)
including SREBP-2, a master regulator of cholesterol synthesis. Through
incompletely understood mechanisms, activated mTORC1 triggers translocation of
SREBP-2, an endoplasmic reticulum (ER) resident protein, to the Golgi where SREBP
2 is cleaved to translocate to the nucleus and activate gene expression for
cholesterol synthesis. Low ER cholesterol is a well-established trigger for SREBP
2 activation. We thus investigated whether mTORC1 activates SREBP-2 by reducing
cholesterol delivery to the ER. We report here that mTORC1 activation is
accompanied by low ER cholesterol and an increase of SREBP-2 activation.
Conversely, a decrease in mTORC1 activity coincides with a rise in ER cholesterol
and a decrease in SERBP-2 activity. This rise in ER cholesterol is of lysosomal
origin: blocking the exit of cholesterol from lysosomes by U18666A or NPC1 siRNA
prevents ER cholesterol from increasing and, consequently, SREBP-2 is activated
without mTORC1 activation. Furthermore, when mTORC1 activity is low, cholesterol
is delivered to lysosomes through two membrane trafficking pathways: autophagy
and rerouting of endosomes to lysosomes. Indeed, with dual blockade of both
pathways by Atg5-/- and dominant-negative rab5, ER cholesterol fails to increase
when mTORC1 activity is low, and SREBP-2 is activated. Conversely, overexpressing
constitutively active Atg7, which forces autophagy and raises ER cholesterol even
when mTORC1 activity is high, suppresses SREBP-2 activation. We conclude that
mTORC1 actively suppresses autophagy and maintains endosomal recycling, thereby
preventing endosomes and autophagosomes from reaching lysosomes. This results in
a reduction of cholesterol in the ER and activation of SREBP-2.
PMID- 28696298
TI - Functional characterization of odorant receptors in the ponerine ant,
Harpegnathos saltator.
AB - Animals use a variety of sensory modalities-including visual, acoustic, and
chemical-to sense their environment and interact with both conspecifics and other
species. Such communication is especially critical in eusocial insects such as
honey bees and ants, where cooperation is critical for survival and reproductive
success. Various classes of chemoreceptors have been hypothesized to play
essential roles in the origin and evolution of eusociality in ants, through their
functional roles in pheromone detection that characterizes reproductive status
and colony membership. To better understand the molecular mechanisms by which
chemoreceptors regulate social behaviors, we investigated the roles of a critical
class of chemoreceptors, the odorant receptors (ORs), from the ponerine ant
Harpegnathos saltator in detecting cuticular hydrocarbon pheromones. In light of
the massive OR expansion in ants (~400 genes per species), a representative
survey based on phylogenetic and transcriptomic criteria was carried out across
discrete odorant receptor subfamilies. Responses to several classes of
semiochemicals are described, including cuticular hydrocarbons and mandibular
gland components that act as H. saltator pheromones, and a range of more
traditional general odorants. When viewed through the prism of caste-specific OR
enrichment and distinctive OR subfamily odorant response profiles, our findings
suggest that whereas individual HsOrs appear to be narrowly tuned, there is no
apparent segregation of tuning responses within any discrete HsOr subfamily.
Instead, the HsOR gene family as a whole responds to a broad array of compounds,
including both cuticular hydrocarbons and general odorants that are likely to
mediate distinct behaviors.
PMID- 28696299
TI - Polar delivery of Legionella type IV secretion system substrates is essential for
virulence.
AB - A recurrent emerging theme is the targeting of proteins to subcellular
microdomains within bacterial cells, particularly to the poles. In most cases, it
has been assumed that this localization is critical to the protein's function.
Legionella pneumophila uses a type IVB secretion system (T4BSS) to export a large
number of protein substrates into the cytoplasm of host cells. Here we show that
the Legionella export apparatus is localized to the bacterial poles, as is
consistent with many T4SS substrates being retained on the phagosomal membrane
adjacent to the poles of the bacterium. More significantly, we were able to
demonstrate that polar secretion of substrates is critically required for
Legionella's alteration of the host endocytic pathway, an activity required for
this pathogen's virulence.
PMID- 28696300
TI - Acetylcholine-producing NK cells attenuate CNS inflammation via modulation of
infiltrating monocytes/macrophages.
AB - The nonneural cholinergic system of immune cells is pivotal for the maintenance
of immunological homeostasis. Here we demonstrate the expression of choline
acetyltransferase (ChAT) and cholinergic enzymes in murine natural killer (NK)
cells. The capacity for acetylcholine synthesis by NK cells increased markedly
under inflammatory conditions such as experimental autoimmune encephalomyelitis
(EAE), in which ChAT expression escalated along with the maturation of NK cells.
ChAT+ and ChAT- NK cells displayed distinctive features in terms of cytotoxicity
and chemokine/cytokine production. Transfer of ChAT+ NK cells into the cerebral
ventricles of CX3CR1-/- mice reduced brain and spinal cord damage after EAE
induction, and decreased the numbers of CNS-infiltrating CCR2+Ly6Chi monocytes.
ChAT+ NK cells killed CCR2+Ly6Chi monocytes directly via the disruption of
tolerance and inhibited the production of proinflammatory cytokines.
Interestingly, ChAT+ NK cells and CCR2+Ly6Chi monocytes formed immune synapses;
moreover, the impact of ChAT+ NK cells was mediated by alpha7-nicotinic
acetylcholine receptors. Finally, the NK cell cholinergic system up-regulated in
response to autoimmune activation in multiple sclerosis, perhaps reflecting the
severity of disease. Therefore, this study extends our understanding of the
nonneural cholinergic system and the protective immune effect of acetylcholine
producing NK cells in autoimmune diseases.
PMID- 28696301
TI - Otoferlin is a multivalent calcium-sensitive scaffold linking SNAREs and calcium
channels.
AB - Sensory hair cells rely on otoferlin as the calcium sensor for exocytosis and
encoding of sound preferentially over the neuronal calcium sensor synaptotagmin.
Although it is established that synaptotagmin cannot rescue the otoferlin KO
phenotype, the large size and low solubility of otoferlin have prohibited direct
biochemical comparisons that could establish functional differences between these
two proteins. To address this challenge, we have developed a single-molecule
colocalization binding titration assay (smCoBRA) that can quantitatively
characterize full-length otoferlin from mammalian cell lysate. Using smCoBRA, we
found that, although both otoferlin and synaptotagmin bind membrane fusion SNARE
proteins, only otoferlin interacts with the L-type calcium channel Cav1.3,
showing a significant difference between the synaptic proteins. Furthermore,
otoferlin was found capable of interacting with multiple SNARE and Cav1.3
proteins simultaneously, forming a heterooligomer complex. We also found that a
deafness-causing missense mutation in otoferlin attenuates binding between
otoferlin and Cav1.3, suggesting that deficiencies in this interaction may form
the basis for otoferlin-related hearing loss. Based on our results, we propose a
model in which otoferlin acts as a calcium-sensitive scaffolding protein,
localizing SNARE proteins proximal to the calcium channel so as to synchronize
calcium influx with membrane fusion. Our findings also provide a molecular-level
explanation for the observation that synaptotagmin and otoferlin are not
functionally redundant. This study also validates a generally applicable
methodology for quantitatively characterizing large, multivalent membrane
proteins.
PMID- 28696302
TI - Harm to self outweighs benefit to others in moral decision making.
AB - How we make decisions that have direct consequences for ourselves and others
forms the moral foundation of our society. Whereas economic theory contends that
humans aim at maximizing their own gains, recent seminal psychological work
suggests that our behavior is instead hyperaltruistic: We are more willing to
sacrifice gains to spare others from harm than to spare ourselves from harm. To
investigate how such egoistic and hyperaltruistic tendencies influence moral
decision making, we investigated trade-off decisions combining monetary rewards
and painful electric shocks, administered to the participants themselves or an
anonymous other. Whereas we replicated the notion of hyperaltruism (i.e., the
willingness to forego reward to spare others from harm), we observed strongly
egoistic tendencies in participants' unwillingness to harm themselves for others'
benefit. The moral principle guiding intersubject trade-off decision making
observed in our study is best described as egoistically biased altruism, with
important implications for our understanding of economic and social interactions
in our society.
PMID- 28696303
TI - Intestinal virome changes precede autoimmunity in type I diabetes-susceptible
children.
AB - Viruses have long been considered potential triggers of autoimmune diseases. Here
we defined the intestinal virome from birth to the development of autoimmunity in
children at risk for type 1 diabetes (T1D). A total of 220 virus-enriched
preparations from serially collected fecal samples from 11 children (cases) who
developed serum autoantibodies associated with T1D (of whom five developed
clinical T1D) were compared with samples from controls. Intestinal viromes of
case subjects were less diverse than those of controls. Among eukaryotic viruses,
we identified significant enrichment of Circoviridae-related sequences in samples
from controls in comparison with cases. Enterovirus, kobuvirus, parechovirus,
parvovirus, and rotavirus sequences were frequently detected but were not
associated with autoimmunity. For bacteriophages, we found higher Shannon
diversity and richness in controls compared with cases and observed that changes
in the intestinal virome over time differed between cases and controls. Using
Random Forests analysis, we identified disease-associated viral bacteriophage
contigs after subtraction of age-associated contigs. These disease-associated
contigs were statistically linked to specific components of the bacterial
microbiome. Thus, changes in the intestinal virome preceded autoimmunity in this
cohort. Specific components of the virome were both directly and inversely
associated with the development of human autoimmune disease.
PMID- 28696304
TI - Bioinspired supramolecular fibers drawn from a multiphase self-assembled
hydrogel.
AB - Inspired by biological systems, we report a supramolecular polymer-colloidal
hydrogel (SPCH) composed of 98 wt % water that can be readily drawn into uniform
([Formula: see text]6-[Formula: see text]m thick) "supramolecular fibers" at room
temperature. Functionalized polymer-grafted silica nanoparticles, a
semicrystalline hydroxyethyl cellulose derivative, and cucurbit[8]uril undergo
aqueous self-assembly at multiple length scales to form the SPCH facilitated by
host-guest interactions at the molecular level and nanofibril formation at
colloidal-length scale. The fibers exhibit a unique combination of stiffness and
high damping capacity (60-70%), the latter exceeding that of even biological
silks and cellulose-based viscose rayon. The remarkable damping performance of
the hierarchically structured fibers is proposed to arise from the complex
combination and interactions of "hard" and "soft" phases within the SPCH and its
constituents. SPCH represents a class of hybrid supramolecular composites,
opening a window into fiber technology through low-energy manufacturing.
PMID- 28696305
TI - Interannual cycles of Hantaan virus outbreaks at the human-animal interface in
Central China are controlled by temperature and rainfall.
AB - Hantavirus, a rodent-borne zoonotic pathogen, has a global distribution with
200,000 human infections diagnosed annually. In recent decades, repeated
outbreaks of hantavirus infections have been reported in Eurasia and America.
These outbreaks have led to public concern and an interest in understanding the
underlying biological mechanisms. Here, we propose a climate-animal-Hantaan virus
(HTNV) infection model to address this issue, using a unique dataset spanning a
54-y period (1960-2013). This dataset comes from Central China, a focal point for
natural HTNV infection, and includes both field surveillance and an
epidemiological record. We reveal that the 8-y cycle of HTNV outbreaks is driven
by the confluence of the cyclic dynamics of striped field mouse (Apodemus
agrarius) populations and climate variability, at both seasonal and interannual
cycles. Two climatic variables play key roles in the ecology of the HTNV system:
temperature and rainfall. These variables account for the dynamics in the host
reservoir system and markedly affect both the rate of transmission and the
potential risk of outbreaks. Our results suggest that outbreaks of HTNV infection
occur only when climatic conditions are favorable for both rodent population
growth and virus transmission. These findings improve our understanding of how
climate drives the periodic reemergence of zoonotic disease outbreaks over long
timescales.
PMID- 28696306
TI - Continuous immunotypes describe human immune variation and predict diverse
responses.
AB - The immune system consists of many specialized cell populations that communicate
with each other to achieve systemic immune responses. Our analyses of various
measured immune cell population frequencies in healthy humans and their responses
to diverse stimuli show that human immune variation is continuous in nature,
rather than characterized by discrete groups of similar individuals. We show that
the same three key combinations of immune cell population frequencies can define
an individual's immunotype and predict a diverse set of functional responses to
cytokine stimulation. We find that, even though interindividual variations in
specific cell population frequencies can be large, unrelated individuals of
younger age have more homogeneous immunotypes than older individuals. Across age
groups, cytomegalovirus seropositive individuals displayed immunotypes
characteristic of older individuals. The conceptual framework for defining
immunotypes suggested by our results could guide the development of better
therapies that appropriately modulate collective immunotypes, rather than
individual immune components.
PMID- 28696307
TI - Modeling adsorption properties of structurally deformed metal-organic frameworks
using structure-property map.
AB - Structural deformation and collapse in metal-organic frameworks (MOFs) can lead
to loss of long-range order, making it a challenge to model these amorphous
materials using conventional computational methods. In this work, we show that a
structure-property map consisting of simulated data for crystalline MOFs can be
used to indirectly obtain adsorption properties of structurally deformed MOFs.
The structure-property map (with dimensions such as Henry coefficient, heat of
adsorption, and pore volume) was constructed using a large data set of over 12000
crystalline MOFs from molecular simulations. By mapping the experimental data
points of deformed SNU-200, MOF-5, and Ni-MOF-74 onto this structure-property
map, we show that the experimentally deformed MOFs share similar adsorption
properties with their nearest neighbor crystalline structures. Once the nearest
neighbor crystalline MOFs for a deformed MOF are selected from a structure
property map at a specific condition, then the adsorption properties of these
MOFs can be successfully transformed onto the degraded MOFs, leading to a new way
to obtain properties of materials whose structural information is lost.
PMID- 28696308
TI - tsRNA signatures in cancer.
AB - Small, noncoding RNAs are short untranslated RNA molecules, some of which have
been associated with cancer development. Recently we showed that a class of small
RNAs generated during the maturation process of tRNAs (tRNA-derived small RNAs,
hereafter "tsRNAs") is dysregulated in cancer. Specifically, we uncovered tsRNA
signatures in chronic lymphocytic leukemia and lung cancer and demonstrated that
the ts-4521/3676 cluster (now called "ts-101" and "ts-53," respectively), ts-46,
and ts-47 are down-regulated in these malignancies. Furthermore, we showed that
tsRNAs are similar to Piwi-interacting RNAs (piRNAs) and demonstrated that ts-101
and ts-53 can associate with PiwiL2, a protein involved in the silencing of
transposons. In this study, we extended our investigation on tsRNA signatures to
samples collected from patients with colon, breast, or ovarian cancer and cell
lines harboring specific oncogenic mutations and representing different stages of
cancer progression. We detected tsRNA signatures in all patient samples and
determined that tsRNA expression is altered upon oncogene activation and during
cancer staging. In addition, we generated a knocked-out cell model for ts-101 and
ts-46 in HEK-293 cells and found significant differences in gene-expression
patterns, with activation of genes involved in cell survival and down-regulation
of genes involved in apoptosis and chromatin structure. Finally, we overexpressed
ts-46 and ts-47 in two lung cancer cell lines and performed a clonogenic assay to
examine their role in cell proliferation. We observed a strong inhibition of
colony formation in cells overexpressing these tsRNAs compared with untreated
cells, confirming that tsRNAs affect cell growth and survival.
PMID- 28696309
TI - Influenza infection triggers disease in a genetic model of experimental
autoimmune encephalomyelitis.
AB - Multiple sclerosis (MS) is an autoimmune disease of the central nervous system.
Most MS patients experience periods of symptom exacerbation (relapses) followed
by periods of partial recovery (remission). Interestingly, upper-respiratory
viral infections increase the risk for relapse. Here, we used an autoimmune-prone
T-cell receptor transgenic mouse (2D2) and a mouse-adapted human influenza virus
to test the hypothesis that upper-respiratory viral infection can cause glial
activation, promote immune cell trafficking to the CNS, and trigger disease.
Specifically, we inoculated 2D2 mice with influenza A virus (Puerto Rico/8/34;
PR8) and then monitored them for symptoms of inflammatory demyelination. Clinical
and histological experimental autoimmune encephalomyelitis was observed in ~29%
of infected 2D2 mice. To further understand how peripheral infection could
contribute to disease onset, we inoculated wild-type C57BL/6 mice and measured
transcriptomic alterations occurring in the cerebellum and spinal cord and
monitored immune cell surveillance of the CNS by flow cytometry. Infection caused
temporal alterations in the transcriptome of both the cerebellum and spinal cord
that was consistent with glial activation and increased T-cell, monocyte, and
neutrophil trafficking to the brain at day 8 post infection. Finally, Cxcl5
expression was up-regulated in the brains of influenza-infected mice and was
elevated in cerebrospinal fluid of MS patients during relapse compared with
specimens acquired during remission. Collectively, these data identify a
mechanism by which peripheral infection may exacerbate MS as well as other
neurological diseases.
PMID- 28696310
TI - Antibody-induced uncoating of human rhinovirus B14.
AB - Rhinoviruses (RVs) are the major causes of common colds in humans. They have a
nonenveloped, icosahedral capsid surrounding a positive-strand RNA genome. Here
we report that the antigen-binding (Fab) fragment of a neutralizing antibody (C5)
can trigger genome release from RV-B14 to form emptied particles and neutralize
virus infection. Using cryo-electron microscopy, structures of the C5 Fab in
complex with the full and emptied particles have been determined at 2.3 A and 3.0
A resolution, respectively. Each of the 60 Fab molecules binds primarily to a
region on viral protein 3 (VP3). Binding of the C5 Fabs to RV-B14 results in
significant conformational changes around holes in the capsid through which the
viral RNA might exit. These results are so far the highest resolution view of an
antibody-virus complex and elucidate a mechanism whereby antibodies neutralize
RVs and related viruses by inducing virus uncoating.
PMID- 28696311
TI - Escherichia coli cytochrome c peroxidase is a respiratory oxidase that enables
the use of hydrogen peroxide as a terminal electron acceptor.
AB - Microbial cytochrome c peroxidases (Ccp) have been studied for 75 years, but
their physiological roles are unclear. Ccps are located in the periplasms of
bacteria and the mitochondrial intermembrane spaces of fungi. In this study, Ccp
is demonstrated to be a significant degrader of hydrogen peroxide in anoxic
Escherichia coli Intriguingly, ccp transcription requires both the presence of
H2O2 and the absence of O2 Experiments show that Ccp lacks enough activity to
shield the cytoplasm from exogenous H2O2 However, it receives electrons from the
quinone pool, and its flux rate approximates flow to other anaerobic electron
acceptors. Indeed, Ccp enabled E. coli to grow on a nonfermentable carbon source
when H2O2 was supplied. Salmonella behaved similarly. This role rationalizes ccp
repression in oxic environments. We speculate that micromolar H2O2 is created
both biologically and abiotically at natural oxic/anoxic interfaces. The OxyR
response appears to exploit this H2O2 as a terminal oxidant while simultaneously
defending the cell against its toxicity.
PMID- 28696312
TI - Functional characterization of human pluripotent stem cell-derived arterial
endothelial cells.
AB - Here, we report the derivation of arterial endothelial cells from human
pluripotent stem cells that exhibit arterial-specific functions in vitro and in
vivo. We combine single-cell RNA sequencing of embryonic mouse endothelial cells
with an EFNB2-tdTomato/EPHB4-EGFP dual reporter human embryonic stem cell line to
identify factors that regulate arterial endothelial cell specification. The
resulting xeno-free protocol produces cells with gene expression profiles, oxygen
consumption rates, nitric oxide production levels, shear stress responses, and
TNFalpha-induced leukocyte adhesion rates characteristic of arterial endothelial
cells. Arterial endothelial cells were robustly generated from multiple human
embryonic and induced pluripotent stem cell lines and have potential applications
for both disease modeling and regenerative medicine.
PMID- 28696313
TI - Behavioral self-organization underlies the resilience of a coastal ecosystem.
AB - Self-organized spatial patterns occur in many terrestrial, aquatic, and marine
ecosystems. Theoretical models and observational studies suggest self
organization, the formation of patterns due to ecological interactions, is
critical for enhanced ecosystem resilience. However, experimental tests of this
cross-ecosystem theory are lacking. In this study, we experimentally test the
hypothesis that self-organized pattern formation improves the persistence of
mussel beds (Mytilus edulis) on intertidal flats. In natural beds, mussels
generate self-organized patterns at two different spatial scales: regularly
spaced clusters of mussels at centimeter scale driven by behavioral aggregation
and large-scale, regularly spaced bands at meter scale driven by ecological
feedback mechanisms. To test for the relative importance of these two spatial
scales of self-organization on mussel bed persistence, we conducted field
manipulations in which we factorially constructed small-scale and/or large-scale
patterns. Our results revealed that both forms of self-organization enhanced the
persistence of the constructed mussel beds in comparison to nonorganized beds.
Small-scale, behaviorally driven cluster patterns were found to be crucial for
persistence, and thus resistance to wave disturbance, whereas large-scale, self
organized patterns facilitated reformation of small-scale patterns if mussels
were dislodged. This study provides experimental evidence that self-organization
can be paramount to enhancing ecosystem persistence. We conclude that ecosystems
with self-organized spatial patterns are likely to benefit greatly from
conservation and restoration actions that use the emergent effects of self
organization to increase ecosystem resistance to disturbance.
PMID- 28696315
TI - Size and mobility of lipid domains tuned by geometrical constraints.
AB - In the plasma membrane of eukaryotic cells, proteins and lipids are organized in
clusters, the latter ones often called lipid domains or "lipid rafts." Recent
findings highlight the dynamic nature of such domains and the key role of
membrane geometry and spatial boundaries. In this study, we used porous
substrates with different pore radii to address precisely the extent of the
geometric constraint, permitting us to modulate and investigate the size and
mobility of lipid domains in phase-separated continuous pore-spanning membranes
(PSMs). Fluorescence video microscopy revealed two types of liquid-ordered (lo)
domains in the freestanding parts of the PSMs: (i) immobile domains that were
attached to the pore rims and (ii) mobile, round-shaped lo domains within the
center of the PSMs. Analysis of the diffusion of the mobile lo domains by video
microscopy and particle tracking showed that the domains' mobility is slowed down
by orders of magnitude compared with the unrestricted case. We attribute the
reduced mobility to the geometric confinement of the PSM, because the drag force
is increased substantially due to hydrodynamic effects generated by the presence
of these boundaries. Our system can serve as an experimental test bed for
diffusion of 2D objects in confined geometry. The impact of hydrodynamics on the
mobility of enclosed lipid domains can have great implications for the formation
and lateral transport of signaling platforms.
PMID- 28696314
TI - Loss-of-function mutation in Mirta22/Emc10 rescues specific schizophrenia-related
phenotypes in a mouse model of the 22q11.2 deletion.
AB - Identification of protective loss-of-function (LoF) mutations holds great promise
for devising novel therapeutic interventions, although it faces challenges due to
the scarcity of protective LoF alleles in the human genome. Exploiting the
detailed mechanistic characterization of animal models of validated disease
mutations offers an alternative. Here, we provide insights into protective
variant biology based on our characterization of a model of the 22q11.2 deletion,
a strong genetic risk factor for schizophrenia (SCZ). Postnatal brain up
regulation of Mirta22/Emc10, an inhibitor of neuronal maturation, represents the
major transcriptional effect of the 22q11.2-associated microRNA dysregulation.
Here, we demonstrate that mice in which the Df(16)A deficiency is combined with a
LoF Mirta22 allele show rescue of key SCZ-related deficits, namely prepulse
inhibition decrease, working memory impairment, and social memory deficits, as
well as synaptic and structural plasticity abnormalities in the prefrontal
cortex. Additional analysis of homozygous Mirta22 knockout mice, in which no
alteration is observed in the above-mentioned SCZ-related phenotypes, highlights
the deleterious effects of Mirta22 up-regulation. Our results support a causal
link between dysregulation of a miRNA target and SCZ-related deficits and provide
key insights into beneficial LoF mutations and potential new treatments.
PMID- 28696316
TI - Light-mediated self-organization of sunflower stands increases oil yield in the
field.
AB - Here, we show a unique crop response to intraspecific interference, whereby
neighboring sunflower plants in a row avoid each other by growing toward a more
favorable light environment and collectively increase production per unit land
area. In high-density stands, a given plant inclined toward one side of the
interrow space, and the immediate neighbors inclined in the opposite direction.
This process started early as an incipient inclination of pioneer plants, and the
arrangement propagated gradually as a "wave" of alternate inclination that
persisted until maturity. Measurements and experimental manipulation of light
spectral composition indicate that these responses are mediated by changes in the
red/far-red ratio of the light, which is perceived by phytochrome. Cellular
automata simulations reproduced the patterns of stem inclination in field
experiments, supporting the proposition of self-organization of stand structure.
Under high crop population densities (10 and 14 plants per m2), as yet
unachievable in commercial farms with current hybrids due to lodging and
diseases, self-organized crops yielded between 19 and 47% more oil than crops
forced to remain erect.
PMID- 28696317
TI - Quinolines block every step of malaria heme crystal growth.
PMID- 28696318
TI - Energetic redistribution in allostery to execute protein function.
PMID- 28696319
TI - Combined epigenetic and differentiation-based treatment inhibits neuroblastoma
tumor growth and links HIF2alpha to tumor suppression.
AB - Neuroblastoma is a pediatric cancer characterized by variable outcomes ranging
from spontaneous regression to life-threatening progression. High-risk
neuroblastoma patients receive myeloablative chemotherapy with hematopoietic stem
cell transplant followed by adjuvant retinoid differentiation treatment. However,
the overall survival remains low; hence, there is an urgent need for alternative
therapeutic approaches. One feature of high-risk neuroblastoma is the high level
of DNA methylation of putative tumor suppressors. Combining the reversibility of
DNA methylation with the differentiation-promoting activity of retinoic acid (RA)
could provide an alternative strategy to treat high-risk neuroblastoma. Here we
show that treatment with the DNA-demethylating drug 5-Aza-deoxycytidine (AZA)
restores high-risk neuroblastoma sensitivity to RA. Combined systemic
distribution of AZA and RA impedes tumor growth and prolongs survival. Genome
wide analysis of treated tumors reveals that this combined treatment rapidly
induces a HIF2alpha-associated hypoxia-like transcriptional response followed by
an increase in neuronal gene expression and a decrease in cell-cycle gene
expression. A small-molecule inhibitor of HIF2alpha activity diminishes the tumor
response to AZA+RA treatment, indicating that the increase in HIF2alpha levels is
a key component in tumor response to AZA+RA. The link between increased HIF2alpha
levels and inhibited tumor growth is reflected in large neuroblastoma patient
datasets. Therein, high levels of HIF2alpha, but not HIF1alpha, significantly
correlate with expression of neuronal differentiation genes and better prognosis
but negatively correlate with key features of high-risk tumors, such as MYCN
amplification. Thus, contrary to previous studies, our findings indicate an
unanticipated tumor-suppressive role for HIF2alpha in neuroblastoma.
PMID- 28696320
TI - Probing large viscosities in glass-formers with nonequilibrium simulations.
AB - For decades, scientists have debated whether supercooled liquids stop flowing
below a glass transition temperature [Formula: see text] or whether motion
continues to slow gradually down to zero temperature. Answering this question is
challenging because human time scales set a limit on the largest measurable
viscosity, and available data are equally well fit to models with opposite
conclusions. Here, we use short simulations to determine the nonequilibrium shear
response of a typical glass-former, squalane. Fits of the data to an Eyring model
allow us to extrapolate predictions for the equilibrium Newtonian viscosity
[Formula: see text] over a range of pressures and temperatures that change
[Formula: see text] by 25 orders of magnitude. The results agree with the
unusually large set of equilibrium and nonequilibrium experiments on squalane and
extend them to higher [Formula: see text] Studies at different pressures and
temperatures are inconsistent with a diverging viscosity at finite temperature.
At all pressures, the predicted viscosity becomes Arrhenius with a single
temperature-independent activation barrier at low temperatures and high
viscosities ([Formula: see text] Pa[Formula: see text]s). Possible experimental
tests of our results are outlined.
PMID- 28696321
TI - How large herbivores subsidize aquatic food webs in African savannas.
PMID- 28696322
TI - Advancing values affirmation as a scalable strategy for mitigating identity
threats and narrowing national achievement gaps.
PMID- 28696324
TI - Regular patterns link individual behavior to population persistence.
PMID- 28696323
TI - Attention model of binocular rivalry.
AB - When the corresponding retinal locations in the two eyes are presented with
incompatible images, a stable percept gives way to perceptual alternations in
which the two images compete for perceptual dominance. As perceptual experience
evolves dynamically under constant external inputs, binocular rivalry has been
used for studying intrinsic cortical computations and for understanding how the
brain regulates competing inputs. Converging behavioral and EEG results have
shown that binocular rivalry and attention are intertwined: binocular rivalry
ceases when attention is diverted away from the rivalry stimuli. In addition, the
competing image in one eye suppresses the target in the other eye through a
pattern of gain changes similar to those induced by attention. These results
require a revision of the current computational theories of binocular rivalry, in
which the role of attention is ignored. Here, we provide a computational model of
binocular rivalry. In the model, competition between two images in rivalry is
driven by both attentional modulation and mutual inhibition, which have distinct
selectivity (feature vs. eye of origin) and dynamics (relatively slow vs.
relatively fast). The proposed model explains a wide range of phenomena reported
in rivalry, including the three hallmarks: (i) binocular rivalry requires
attention; (ii) various perceptual states emerge when the two images are swapped
between the eyes multiple times per second; (iii) the dominance duration as a
function of input strength follows Levelt's propositions. With a bifurcation
analysis, we identified the parameter space in which the model's behavior was
consistent with experimental results.
PMID- 28696326
TI - Comment on "DNA Repair Interacts with Autophagy To Regulate Inflammatory
Responses to Pulmonary Hyperoxia".
PMID- 28696327
TI - Response to Comment on "DNA Repair Interacts with Autophagy To Regulate
Inflammatory Responses to Pulmonary Hyperoxia".
PMID- 28696328
TI - Of Mice, Dirty Mice, and Men: Using Mice To Understand Human Immunology.
AB - Mouse models have enabled breakthroughs in our understanding of the immune
system, but it has become increasingly popular to emphasize their shortcomings
when translating observations to humans. This review provides a brief summary of
mouse natural history, husbandry, and the pros and cons of pursuing basic
research in mice versus humans. Opportunities are discussed for extending the
predictive translational value of mouse research, with an emphasis on
exploitation of a "dirty" mouse model that better mimics the diverse infectious
history that is typical of most humans.
PMID- 28696329
TI - Effect of Tb3+ doping in mixed-valence manganites and cobaltites.
AB - The magnetic ordering of four Tb3+-doped manganites and cobaltites,
La0.7Tb0.1Sr0.2MnO3, La0.7Tb0.1Ca0.2MnO3, La0.7Tb0.1Sr0.2CoO3 and
La0.7Tb0.1Ca0.2CoO3, have been studied by means of neutron diffraction and SQUID
magnetometry. All the samples were prepared by sintering of sol-gel precursors
and their orthorhombic or rhombohedral perovskite structures at room and low
temperatures were refined. A long-range ferromagnetic (FM) order was detected at
the Mn and Co sites. In addition, a small but significant ordered moment was
observed at A sites of studied cobaltites, which was attributed to local Tb3+
moments, aligned by exchange interactions due to FM ordered Co sublattice. No or
minor Tb3+ contribution was detected in studied manganites.
PMID- 28696330
TI - Artificial insect wings with biomimetic wing morphology and mechanical
properties.
AB - The pursuit of a high lift force for insect-scale flapping-wing micro aerial
vehicles (FMAVs) requires that their artificial wings possess biomimetic wing
features which are close to those of their natural counterpart. In this work, we
present both fabrication and testing methods for artificial insect wings with
biomimetic wing morphology and mechanical properties. The artificial cicada
(Hyalessa maculaticollis) wing is fabricated through a high precision laser
cutting technique and a bonding process of multilayer materials. Through
controlling the shape of the wing venation, the fabrication method can achieve
three-dimensional wing architecture, including cambers or corrugations. Besides
the artificial cicada wing, the proposed fabrication method also shows a
promising versatility for diverse wing types. Considering the artificial cicada
wing's characteristics of small size and light weight, special mechanical testing
systems are designed to investigate its mechanical properties. Flexural
stiffness, maximum deformation rate and natural frequency are measured and
compared with those of its natural counterpart. Test results reveal that the
mechanical properties of the artificial cicada wing depend strongly on its vein
thickness, which can be used to optimize an artificial cicada wing's mechanical
properties in the future. As such, this work provides a new form of artificial
insect wings which can be used in the field of insect-scale FMAVs.
PMID- 28696331
TI - Molecular beacon anchored onto a graphene oxide substrate.
AB - In this article, we report a graphene oxide-based nanosensor incorporating
semiconductor quantum dots linked to DNA-aptamers that functions as a 'turn-off'
fluorescent nanosensor for detection of low concentrations of analytes. A
specific demonstration of this turn-off aptasensor is presented for the case of
the detection of mercury (II) ions. In this system, ensembles of aptamer-based
quantum-dot sensors are anchored onto graphene oxide (GO) flakes which provide a
platform for analyte detection in the vicinity of GO. Herein, the operation of
this ensemble-based nanosensor is demonstrated for mercury ions, which upon
addition of mercury, quenching of the emission intensity from the quantum dots is
observed due to resonance energy transfer between quantum dots and the gold
nanoparticle connected via a mercury target aptamer. A key result is that the
usually dominant effect of quenching of the quantum dot due to close proximity to
the GO can be reduced to negligible levels by using a linker molecule in
conjunctions with the aptamer-based nanosensor. The effect of ionic concentration
of the background matrix on the emission intensity was also investigated. The
sensor system is found to be highly selective towards mercury and exhibits a
linear behavior (r 2 > 0.99) in the nanomolar concentration range. The detection
limit of the sensor towards mercury with no GO present was found to be 16.5 nM.
With GO attached to molecular beacon via 14 base, 35 base, and 51 base long
linker DNA, the detection limit was found to be 38.4 nM, 9.45 nM, and 11.38 nM;
respectively.
PMID- 28696332
TI - World Association of Medical Editors (WAME) statement on 'Predatory Journals'.
PMID- 28696333
TI - Cobalt hydroxide nanoflakes and their application as supercapacitors and oxygen
evolution catalysts.
AB - Finding alternative routes to access and store energy has become a major issue
recently. Transition metal oxides have shown promising behaviour as catalysts and
supercapacitors. Recently, liquid exfoliation of bulk metal oxides appears to be
an effective route which provides access to two-dimensional (2D) nano-flakes, the
size of which can be easily selected. These 2D materials exhibit excellent
electrochemical charge storage and catalytic activity for the oxygen evolution
reaction. In this study, various sized selected cobalt hydroxide nano-flake
materials are fabricated by this time efficient and highly reproducible process.
Subsquently, the electrochemical properties of the standard size Co(OH)2
nanoflakes were investigated. The oxide modified electrodes were prepared by
spraying the metal oxide flake suspension onto a porous conductive support
electrode foam, either glassy carbon or nickel. The cobalt hydroxide/nickel foam
system was found to have an overpotential value at 10 mA cm-2 in 1 M NaOH as low
as 280 mV and an associated redox capacitance exhibiting numerical values up to
1500 F g-1, thereby making it a viable dual use electrode.
PMID- 28696334
TI - Recent advances in heart sound analysis.
PMID- 28696335
TI - A double diamond anniversary-Kyshtym and Windscale: the nuclear accidents of
1957.
PMID- 28696336
TI - Perspectives on exhaled nitric oxide.
AB - The history of nitric oxide (NO) in the respiratory field dates back to the
beginning of the 1990s with the pioneering study by Lars Gustafsson et al
describing the presence of endogenous NO in the exhaled breath of human beings.
Soon after, independent studies showed that exhaled NO concentrations (FENO) is
higher in asthmatics than in normal subjects. Not all asthmatics demonstrate a
high FENO, reflecting the heterogeneity of asthma. High values of FENO are
associated with over-expression of corticosteroid-sensitive iNOS isoform and
allergic/eosinophilic inflammation. A major feature of elevated FENO in asthma is
the prediction of inhaled corticosteroid (ICS) response, and FENO more than 50
ppb in adults is a strong indicator of likely ICS sensitivity. In addition, FENO
values are elevated in asthma when asthma control deteriorates, identifying
patients at risk of exacerbations, and, on the other hand, FENO reductions during
ICS therapy precede improvement in respiratory symptoms and lung function,
suggesting that FENO is a sensitive predictor of loss of asthma control. FENO
also predicts the response to biological therapy (anti-IgE, -IL-5 and -IL-13
antibodies) in severe asthma but, interestingly, FENO values fall only after
treatment with anti-IL-13 and -IL-4/IL-13 receptor antibodies. The use of FENO as
a Type-2 inflammatory biomarker, in constellation with other Type-2 markers,
could help to determine who might benefit from ICS and biological treatment. It
remains to find out more precise cut-off values of FENO to identify potential ICS
responders in specific phenotypes.
PMID- 28696337
TI - Memristive device based learning for navigation in robots.
AB - Biomimetic robots have gained attention recently for various applications ranging
from resource hunting to search and rescue operations during disasters.
Biological species are known to intuitively learn from the environment, gather
and process data, and make appropriate decisions. Such sophisticated computing
capabilities in robots are difficult to achieve, especially if done in real-time
with ultra-low energy consumption. Here, we present a novel memristive device
based learning architecture for robots. Two terminal memristive devices with
resistive switching of oxide layer are modeled in a crossbar array to develop a
neuromorphic platform that can impart active real-time learning capabilities in a
robot. This approach is validated by navigating a robot vehicle in an unknown
environment with randomly placed obstacles. Further, the proposed scheme is
compared with reinforcement learning based algorithms using local and global
knowledge of the environment. The simulation as well as experimental results
corroborate the validity and potential of the proposed learning scheme for
robots. The results also show that our learning scheme approaches an optimal
solution for some environment layouts in robot navigation.
PMID- 28696338
TI - Black holes in loop quantum gravity.
AB - This is a review of results on black hole physics in the context of loop quantum
gravity. The key feature underlying these results is the discreteness of
geometric quantities at the Planck scale predicted by this approach to quantum
gravity. Quantum discreteness follows directly from the canonical quantization
prescription when applied to the action of general relativity that is suitable
for the coupling of gravity with gauge fields, and especially with fermions.
Planckian discreteness and causal considerations provide the basic structure for
the understanding of the thermal properties of black holes close to equilibrium.
Discreteness also provides a fresh new look at more (at the moment) speculative
issues, such as those concerning the fate of information in black hole
evaporation. The hypothesis of discreteness leads, also, to interesting
phenomenology with possible observational consequences. The theory of loop
quantum gravity is a developing program; this review reports its achievements and
open questions in a pedagogical manner, with an emphasis on quantum aspects of
black hole physics.
PMID- 28696339
TI - Dose estimation to eye lens of industrial gamma radiography workers using the
Monte Carlo method.
AB - The ICRP Statement on Tissue Reactions (2011), based on epidemiological evidence,
recommended a reduction for the eye lens equivalent dose limit from 150 to 20 mSv
per year. This paper presents mainly the dose estimations received by industrial
gamma radiography workers, during planned or accidental exposure to the eye lens,
Hp(10) and effective dose. A Brazilian Visual Monte Carlo Dose Calculation
program was used and two relevant scenarios were considered. For the planned
exposure situation, twelve radiographic exposures per day for 250 days per year,
which leads to a direct exposure of 10 h per year, were considered. The
simulation was carried out using a 192Ir source with 1.0 TBq of activity; a
source/operator distance between 5 and 10 m and placed at heights of 0.02 m, 1 m
and 2 m, and an exposure time of 12 s. Using a standard height of 1 m, the eye
lens doses were estimated as being between 16.3 and 60.3 mGy per year. For the
accidental exposure situation, the same radionuclide and activity were used, but
in this case the doses were calculated with and without a collimator. The heights
above ground considered were 1.0 m, 1.5 m and 2.0 m; the source/operator distance
was 40 cm, and the exposure time 74 s. The eye lens doses at 1.5 m were 12.3 and
0.28 mGy without and with a collimator, respectively. The conclusions were that:
(1) the estimated doses show that the 20 mSv annual limit for eye lens equivalent
dose can directly impact industrial gamma radiography activities, mainly in
industries with high number of radiographic exposures per year; (2) the risk of
lens opacity has a low probability for a single accident, but depending on the
number of accidental exposures and the dose levels found in planned exposures,
the threshold dose can easily be exceeded during the professional career of an
industrial radiography operator, and; (3) in a first approximation, Hp(10) can be
used to estimate the equivalent dose to the eye lens.
PMID- 28696340
TI - Brain-actuated gait trainer with visual and proprioceptive feedback.
AB - OBJECTIVE: Brain-machine interfaces (BMIs) have been proposed in closed-loop
applications for neuromodulation and neurorehabilitation. This study describes
the impact of different feedback modalities on the performance of an EEG-based
BMI that decodes motor imagery (MI) of leg flexion and extension. APPROACH: We
executed experiments in a lower-limb gait trainer (the legoPress) where nine able
bodied subjects participated in three consecutive sessions based on a crossover
design. A random forest classifier was trained from the offline session and
tested online with visual and proprioceptive feedback, respectively. Post-hoc
classification was conducted to assess the impact of feedback modalities and
learning effect (an improvement over time) on the simulated trial-based
performance. Finally, we performed feature analysis to investigate the
discriminant power and brain pattern modulations across the subjects. MAIN
RESULTS: (i) For real-time classification, the average accuracy was [Formula: see
text]% and [Formula: see text]% for the two online sessions. The results were
significantly higher than chance level, demonstrating the feasibility to
distinguish between MI of leg extension and flexion. (ii) For post-hoc
classification, the performance with proprioceptive feedback ([Formula: see
text]%) was significantly better than with visual feedback ([Formula: see
text]%), while there was no significant learning effect. (iii) We reported
individual discriminate features and brain patterns associated to each feedback
modality, which exhibited differences between the two modalities although no
general conclusion can be drawn. SIGNIFICANCE: The study reported a closed-loop
brain-controlled gait trainer, as a proof of concept for neurorehabilitation
devices. We reported the feasibility of decoding lower-limb movement in an
intuitive and natural way. As far as we know, this is the first online study
discussing the role of feedback modalities in lower-limb MI decoding. Our results
suggest that proprioceptive feedback has an advantage over visual feedback, which
could be used to improve robot-assisted strategies for motor training and
functional recovery.
PMID- 28696341
TI - Capacitive behavior of carbon nanotube thin film induced by deformed ZnO
microspheres.
AB - Multiwalled carbon nanotubes (CNTs) are uniformly distributed with piezoelectric
microspheres. This leads to a large strain gradient due to an induced capacitive
response, providing a 250% enhancement in electromechanical response compared
with pristine CNTs. The fabricated large-area flexible thin film exhibits
excellent pressure sensitivity, which can even detect an arterial pulse with a
much faster response time (~79 ms) in a bendable configuration. In addition, the
film shows a rapid relaxation time (~0.4 s), high stability and excellent
durability with a rapid loading-unloading cycle. The dominant contribution of
piezoelectric microspheres in a CNT matrix as opposed to nanoparticles showed a
much higher sensitivity due to the large change in capacitance. Therefore, hybrid
microstructures have various potential applications in wearable smart
electronics, including detection of human motion and wrist pulses.
PMID- 28696342
TI - Single In x Ga1-x As nanowire/p-Si heterojunction based nano-rectifier diode.
AB - Nanoscale power supply units will be indispensable for fabricating next
generation smart nanoelectronic integrated circuits. Fabrication of nanoscale
rectifier circuits on a Si platform is required for integrating nanoelectronic
devices with on-chip power supply units. In the present study, a nanorectifier
diode based on a single standalone In x Ga1-x As nanowire/p-Si (111)
heterojunction fabricated by metal organic chemical vapor deposition technique
has been studied. The nanoheterojunction diodes have shown good rectification and
fast switching characteristics. The rectification characteristics of the
nanoheterojunction have been demonstrated by different standard waveforms of
sinusoidal, square, sawtooth and triangular for two different frequencies of 1
and 0.1 Hz. Reverse recovery time of around 150 ms has been observed in all wave
response. A half wave rectifier circuit with a simple capacitor filter has been
assembled with this nanoheterojunction diode which provides 12% output
efficiency. The transport of carriers through the heterojunction is investigated.
The interface states density of the nanoheterojunction has also been determined.
Occurrence of output waveforms incommensurate with the input is attributed to
higher series resistance of the diode which is further explained considering the
dimension of p-side and n-side of the junction. The sudden change of ideality
factor after 1.7 V bias is attributed to recombination through interface states
in space charge region. Low interface states density as well as high
rectification ratio makes this heterojunction diode a promising candidate for
future nanoscale electronics.
PMID- 28696343
TI - Novel Surgical Technique of Peeled Internal Limiting Membrane Reposition for
Idiopathic Macular Holes.
PMID- 28696344
TI - HIV and Obesity Comorbidity Increase Interleukin 6 but Not Soluble CD14 or D
Dimer.
AB - OBJECTIVES: Obesity prevalence among people living with HIV (HIV+) is rising. HIV
and obesity are proinflammatory states, but their combined effect on inflammation
(measured by interleukin 6, IL-6), altered coagulation (D-dimer), and monocyte
activation (soluble CD14, sCD14) is unknown. We hypothesized inflammation
increases when obesity and HIV infection co-occur. METHODS: The Veterans Aging
Cohort Study survey cohort is a prospective, observational study of predominantly
male HIV+ veterans and veterans uninfected with HIV; a subset provided blood
samples. Inclusion criteria for this analysis were body mass index >= 18.5 kg/m
and biomarker measurement. Dependent variables were IL-6, sCD14, and D-dimer
quartiles. Obesity/HIV status was the primary predictor. Unadjusted and adjusted
logistic regression models were constructed. RESULTS: Data were analyzed for 1477
HIV+ and 823 uninfected participants. Unadjusted median IL-6 levels were
significantly higher and sCD14 levels significantly lower in obese/HIV+ compared
with nonobese/uninfected (P <0.01 for both). In adjusted analyses, the odds ratio
for increased IL-6 in obese/HIV+ patients was 1.76 (95% confidence interval: 1.18
to 2.47) compared with nonobese/uninfected, and obesity/HIV+ remained associated
with lower odds of elevated sCD14. We did not detect a synergistic association of
co-occurring HIV and obesity on IL-6 or sCD14 elevation. D-dimer levels did not
differ significantly between body mass index/HIV status groups. CONCLUSIONS: HIV
obesity comorbidity is associated with elevated IL-6, decreases in sCD14, and no
significant difference in D-dimer. These findings are clinically significant, as
previous studies associated these biomarkers with mortality. Future studies
should assess whether other biomarkers show similar trends and potential
mechanisms for unanticipated sCD14 and D-dimer findings.
PMID- 28696345
TI - Optimal HIV Postexposure Prophylaxis Regimen Completion With Single Tablet Daily
Elvitegravir/Cobicistat/Tenofovir Disoproxil Fumarate/Emtricitabine Compared With
More Frequent Dosing Regimens.
AB - STRUCTURE: The study evaluated elvitegravir/cobicistat/tenofovir disoproxil
fumarate (TDF)/emtricitabine (FTC) ("Quad pill") for postexposure prophylaxis
(PEP). BACKGROUND: HIV-exposed individuals may benefit from PEP, but completion
rates have been suboptimal because of regimen complexity and side effects. Newer
antiretroviral combinations coformulated as single daily pills may optimize PEP
adherence. SETTING: One hundred HIV-uninfected individuals who presented to a
Boston community health center after an acute HIV sexual exposure were enrolled
and initiated PEP with the daily, single-pill combination Quad pill for a 28-day
course. METHODS: Side effects and medication completion rates from study
participants were compared with historical controls who had used PEP regimens
consisting of TDF/FTC daily and raltegravir twice daily, or earlier regimens of
twice daily zidovudine (AZT)/lamivudine (3TC) and a protease inhibitor, using chi
tests for independence. RESULTS: Of the 100 participants who initiated the Quad
pill for PEP after a high-risk sexual exposure, 71% completed the 28-day Quad
pill regimen, which was significantly greater than historical controls who used
TDF/FTC and raltegravir (57%, P < 0.05) or AZT/3TC plus a protease inhibitor
(39%, P < 0.001). The most common side effects reported by Quad pill users were
as follows: abdominal discomfort or pain, gas or bloating (42%), diarrhea (38%),
fatigue (28%), nausea or vomiting (28%), headache (14%), or dizziness or
lightheadedness (6%). Most symptoms were mild, limited, and did not result in
medication discontinuation. No participants became HIV infected. CONCLUSIONS:
Fixed-dose combination of elvitegravir/cobicistat/TDF/FTC was safe and well
tolerated for PEP, with higher regimen completion rates than more frequently
dosed PEP regimens.
PMID- 28696346
TI - The ART Advantage: Health Care Utilization for Diabetes and Hypertension in Rural
South Africa.
AB - BACKGROUND: The prevalence of diabetes and hypertension has increased in HIV
positive populations, but there is limited understanding of the role that
antiretroviral therapy (ART) programs play in the delivery of services for these
conditions. The aim of this study is to assess the relationship between ART use
and utilization of health care services for diabetes and hypertension. METHODS:
Health and Aging in Africa: A Longitudinal Study of an INDEPTH Community in South
Africa is a cohort of 5059 adults. The baseline study collects biomarker-based
data on HIV, ART, diabetes, and hypertension and self-reported data on health
care utilization. We calculated differences in care utilization for diabetes and
hypertension by HIV and ART status and used multivariable logistic regressions to
estimate the relationship between ART use and utilization of services for these
conditions, controlling for age, sex, body mass index, education, and household
wealth quintile. RESULTS: Mean age, body mass index, hypertension, and diabetes
prevalence were lower in the HIV-positive population (all P < 0.001).
Multivariable logistic regression showed that ART use was significantly
associated with greater odds of blood pressure measurement [adjusted odds ratio
(aOR) 1.27, 95% confidence interval (CI): 1.04 to 1.55] and blood sugar
measurement (aOR 1.26, 95% CI: 1.05 to 1.51), counseling regarding exercise (aOR
1.57, 95% CI: 1.11 to 2.22), awareness of hypertension diagnosis (aOR 1.52, 95%
CI: 1.12 to 2.05), and treatment for hypertension (aOR 1.63, 95% CI: 1.21 to
2.19). CONCLUSIONS: HIV-positive patients who use ART are more likely to have
received health care services for diabetes and hypertension. This apparent ART
advantage suggests that ART programs may be a vehicle for strengthening health
systems for chronic care.
PMID- 28696347
TI - Building Health System Capacity Through Implementation Research: Experience of
INSPIRE-A Multi-country PMTCT Implementation Research Project: Erratum.
PMID- 28696348
TI - Relationship of Triamine-Biocide Tolerance of Salmonella enterica Serovar
Senftenberg to Antimicrobial Susceptibility, Serum Resistance and Outer Membrane
Proteins.
AB - A new emerging phenomenon is the association between the incorrect use of
biocides in the process of disinfection in farms and the emergence of cross
resistance in Salmonella populations. Adaptation of the microorganisms to the sub
inhibitory concentrations of the disinfectants is not clear, but may result in an
increase of sensitivity or resistance to antibiotics, depending on the biocide
used and the challenged Salmonella serovar. Exposure of five Salmonella enterica
subsp. enterica serovar Senftenberg (S. Senftenberg) strains to triamine
containing disinfectant did not result in variants with resistance to
antibiotics, but has changed their susceptibility to normal human serum (NHS).
Three biocide variants developed reduced sensitivity to NHS in comparison to the
sensitive parental strains, while two isolates lost their resistance to serum.
For S. Senftenberg, which exhibited the highest triamine tolerance (6 * MIC) and
intrinsic sensitivity to 22.5% and 45% NHS, a downregulation of flagellin and
enolase has been demonstrated, which might suggest a lower adhesion and virulence
of the bacteria. This is the first report demonstrating the influence of biocide
tolerance on NHS resistance. In conclusion, there was a potential in S.
Senftenberg to adjust to the conditions, where the biocide containing triamine
was present. However, the adaptation did not result in the increase of antibiotic
resistance, but manifested in changes within outer membrane proteins' patterns.
The strategy of bacterial membrane proteins' analysis provides an opportunity to
adjust the ways of infection treatments, especially when it is connected to the
life-threating bacteremia caused by Salmonella species.
PMID- 28696349
TI - The Cell Surface Markers Expression in Postmenopausal Women and Relation to
Obesity and Bone Status.
AB - The age-related changes and hormonal deprivation in postmenopausal women are
associated with the immune response alteration. The excessive fat accumulation,
local and systemic inflammation may lead to dysregulation in immune function and
relevant health problems, including obesity and osteoporosis. We analyzed the
expression of cell surface markers in the venous blood specimens, stained with
fluorophores-conjugated monoclonal antibodies and analysed by multicolour flow
cytometry. The significant changes of cytotoxic, naive, and memory T-lymphocytes,
plasmacytoid dendritic cells (DCs) were in postmenopausal women versus fertile
women. Body mass index (BMI) affected markedly the cell surface expression of
CD265/RANK. Osteoporosis is linked to reduced percentage of plasmacytoid DCs, and
elevated natural Treg cells (p < 0.05). The confounding factors such as women
age, BMI, bone mineral density (BMD), waist size and tissue fat affect the
expression of RANK on myeloid DCs and CD40L on T-lymphocytes that might be the
immunophenotypic modulators after menopause.
PMID- 28696350
TI - Synthesis and Study of Fe-Doped Bi2S3 Semimagnetic Nanocrystals Embedded in a
Glass Matrix.
AB - Iron-doped bismuth sulphide (Bi2-xFexS3) nanocrystals have been successfully
synthesized in a glass matrix using the fusion method. Transmission electron
microscopy images and energy dispersive spectroscopy data clearly show that
nanocrystals are formed with an average diameter of 7-9 nm, depending on the
thermic treatment time, and contain Fe in their chemical composition. Magnetic
force microscopy measurements show magnetic phase contrast patterns, providing
further evidence of Fe incorporation in the nanocrystal structure. The electron
paramagnetic resonance spectra displayed Fe3+ typical characteristics, with spin
of 5/2 in the 3d5 electronic state, thereby confirming the expected trivalent
state of Fe ions in the Bi2S3 host structure. Results from the spin polarized
density functional theory simulations, for the bulk Fe-doped Bi2S3 counterpart,
corroborate the experimental fact that the volume of the unit cell decreases with
Fe substitutionally doping at Bi1 and Bi2 sites. The Bader charge analysis
indicated a pseudo valency charge of 1.322|e| on FeBi1 and 1.306|e| on FeBi2
ions, and a spin contribution for the magnetic moment of 5.0 uB per unit cell
containing one Fe atom. Electronic band structures showed that the (indirect)
band gap changes from 1.17 eV for Bi2S3 bulk to 0.71 eV (0.74 eV) for Bi2S3:FeBi1
(Bi2S3:FeBi2). These results are compatible with the 3d5 high-spin state of Fe3+,
and are in agreement with the experimental results, within the density functional
theory accuracy.
PMID- 28696351
TI - Nanoporous Structure Formation in GaSb, InSb, and Ge by Ion Beam Irradiation
under Controlled Point Defect Creation Conditions.
AB - Ion beam irradiation-induced nanoporous structure formation was investigated on
GaSb, InSb, and Ge surfaces via controlled point defect creation using a focused
ion beam (FIB). This paper compares the nanoporous structure formation under the
same extent of point defect creation while changing the accelerating voltage and
ion dose. Although the same number of point defects were created in each case,
different structures were formed on the different surfaces. The depth direction
density of the point defects was an important factor in this trend. The number of
point defects required for nanoporous structure formation was 4 * 1022
vacancies/m2 at a depth of 18 nm under the surface, based on a comparison of
similar nanoporous structure features in GaSb. The nanoporous structure formation
by ion beam irradiation on GaSb, InSb, and Ge surfaces was controlled by the
number and areal distribution of the created point defects.
PMID- 28696352
TI - Characterization of the Fifth Putative Acetylcholinesterase in the Wolf Spider,
Pardosa pseudoannulata.
AB - Background: Acetylcholinesterase (AChE) is an important neurotransmitter
hydrolase in invertebrate and vertebrate nervous systems. The number of AChEs is
various among invertebrate species, with different functions including the
'classical' role in terminating synaptic transmission and other 'non-classical'
roles. Methods: Using rapid amplification of cDNA ends (RACE) technology, a new
putative AChE-encoding gene was cloned from Pardosa pseudoannulata, an important
predatory natural enemy. Sequence analysis and in vitro expression were employed
to determine the structural features and biochemical properties of this putative
AChE. Results: The cloned AChE contained the most conserved motifs of AChEs
family and was clearly clustered with Arachnida AChEs. Determination of
biochemical properties revealed that the recombinant enzyme had the obvious
preference for the substrate ATC (acetylthiocholine iodide) versus BTC
(butyrylthiocholine iodide). The AChE was highly sensitive to AChE-specific
inhibitor BW284C51, but not butyrylcholinesterase-specific inhibitor
tetraisopropyl pyrophosphoramide (ISO-OMPA). Based on these results, we concluded
that a new AChE was identified from P. pseudoannulata and denoted as PpAChE5.
Conclusion: Here we report the identification of a new AChE from P.
pseudoannulata and increased the AChE number to five in this species. Although
PpAChE5 had the biggest Vmax value among five identified AChEs, it showed
relatively low affinity with ATC. Similar sensitivity to test insecticides
indicated that this AChE might serve as the target for both organophosphorus and
carbamate insecticides.
PMID- 28696353
TI - Array of Chemosensitive Resistors with Composites of Gas Chromatography (GC)
Materials and Carbon Black for Detection and Recognition of VOCs: A Basic Study.
AB - Mimicking the biological olfaction, large odor-sensor arrays can be used to
acquire a broad range of chemical information, with a potentially high degree of
redundancy, to allow for enhanced control over the sensitivity and selectivity of
artificial olfaction systems. The arrays should consist of the largest possible
number of individual sensing elements while being miniaturized. Chemosensitive
resistors are one of the sensing platforms that have a potential to satisfy these
two conditions. In this work we test viability of fabricating a 16-element
chemosensitive resistor array for detection and recognition of volatile organic
compounds (VOCs). The sensors were fabricated using blends of carbon black and
gas chromatography (GC) stationary-phase materials preselected based on their
sorption properties. Blends of the selected GC materials with carbon black
particles were subsequently coated over chemosensitive resistor devices and the
resulting sensors/arrays evaluated in exposure experiments against vapors of
pyrrole, benzenal, nonanal, and 2-phenethylamine at 150, 300, 450, and 900 ppb.
Responses of the fabricated 16-element array were stable and differed for each
individual odorant sample, proving the blends of GC materials with carbon black
particles can be effectively used for fabrication of large odor-sensing arrays
based on chemosensitive resistors. The obtained results suggest that the proposed
sensing devices could be effective in discriminating odor/vapor samples at the
sub-ppm level.
PMID- 28696354
TI - A Case of AML Characterized by a Novel t(4;15)(q31;q22) Translocation That
Confers a Growth-Stimulatory Response to Retinoid-Based Therapy.
AB - Here we report the case of a 30-year-old woman with relapsed acute myeloid
leukemia (AML) who was treated with all-trans retinoic acid (ATRA) as part of
investigational therapy (NCT02273102). The patient died from rapid disease
progression following eight days of continuous treatment with ATRA. Karyotype
analysis and RNA-Seq revealed the presence of a novel t(4;15)(q31;q22) reciprocal
translocation involving the TMEM154 and RASGRF1 genes. Analysis of primary cells
from the patient revealed the expression of TMEM154-RASGRF1 mRNA and the
resulting fusion protein, but no expression of the reciprocal RASGRF1-TMEM154
fusion. Consistent with the response of the patient to ATRA therapy, we observed
a rapid proliferation of t(4;15) primary cells following ATRA treatment ex vivo.
Preliminary characterization of the retinoid response of t(4;15) AML revealed
that in stark contrast to non-t(4;15) AML, these cells proliferate in response to
specific agonists of RARalpha and RARgamma. Furthermore, we observed an increase
in the levels of nuclear RARgamma upon ATRA treatment. In summary, the
identification of the novel t(4;15)(q31;q22) reciprocal translocation opens new
avenues in the study of retinoid resistance and provides potential for a new
biomarker for therapy of AML.
PMID- 28696355
TI - ABCC6 and Pseudoxanthoma Elasticum: The Face of a Rare Disease from Genetics to
Advocacy.
AB - Pseudoxanthoma elasticum (PXE) is an autosomal recessive disorder characterized
by the mineralization of connective tissues in the body. Primary manifestation of
PXE occurs in the tissues of the skin, eyes, and cardiovascular system. PXE is
primarily caused by mutations in the ABCC6 gene. The ABCC6 gene encodes the trans
membrane protein ABCC6, which is highly expressed in the kidneys and liver. PXE
has high phenotypic variability, which may possibly be affected by several
modifier genes. Disease advocacy organizations have had a pivotal role in
bringing rare disease research to the forefront and in helping to sustain
research funding for rare genetic diseases in order to help find a treatment for
these diseases, pseudoxanthoma elasticum included. Because of these initiatives,
individuals affected by these conditions benefit by being scientifically informed
about their condition, having an effective support mechanism, and also by
contributing to scientific research efforts and banking of biological samples.
This rapid progress would not have been possible without the aid of disease
advocacy organizations such as PXE International.
PMID- 28696356
TI - Rapamycin Maintains the Chondrocytic Phenotype and Interferes with Inflammatory
Cytokine Induced Processes.
AB - Osteoarthritis (OA) is hallmarked by a progressive degradation of articular
cartilage. Besides risk factors including trauma, obesity or genetic
predisposition, inflammation has a major impact on the development of this
chronic disease. During the course of inflammation, cytokines such as tumor
necrosis factor-alpha(TNF-alpha) and interleukin (IL)-1beta are secreted by
activated chondrocytes as well as synovial cells and stimulate the production of
other inflammatory cytokines and matrix degrading enzymes. The mTORC1 inhibitor
rapamycin is a clinical approved immunosuppressant and several studies also
verified its chondroprotective effects in OA. However, the effect of blocking the
mechanistic target of rapamycin complex (mTORC)1 on the inflammatory status
within OA is not well studied. Therefore, we aimed to investigate if inhibition
of mTORC1 by rapamycin can preserve and sustain chondrocytes in an inflammatory
environment. Patient-derived chondrocytes were cultured in media supplemented
with or without the mTORC1 inhibitor rapamycin. To establish an inflammatory
environment, either TNF-alpha or IL-1beta was added to the media (=OA-model). The
chondroprotective and anti-inflammatory effects of rapamycin were evaluated using
sulfated glycosaminoglycan (sGAG) release assay, Caspase 3/7 activity assay,
lactate dehydrogenase (LDH) assay and quantitative real time polymerase chain
reaction (PCR). Blocking mTORC1 by rapamycin reduced the release and therefore
degradation of sGAGs, which are components of the extracellular matrix secreted
by chondrocytes. Furthermore, blocking mTORC1 in OA chondrocytes resulted in an
enhanced expression of the main chondrogenic markers. Rapamycin was able to
protect chondrocytes from cell death in an OA-model shown by reduced Caspase 3/7
activity and diminished LDH release. Furthermore, inhibition of mTORC1 preserved
the chondrogenic phenotype of OA chondrocytes, but also reduced inflammatory
processes within the OA-model. This study highlights that blocking mTORC1 is a
new and promising approach for treating OA. Low side effects make rapamycin an
attractive implementation to existing therapeutic strategies. We showed that
rapamycin's chondroprotective property might be due to an interference with IL
1beta triggered inflammatory processes.
PMID- 28696357
TI - MYC-Driven Pathways in Breast Cancer Subtypes.
AB - The transcription factor MYC (MYC proto-oncogene, bHLH transcription factor) is
an essential signaling hub in multiple cellular processes that sustain growth of
many types of cancers. MYC regulates expression of RNA, both protein and non
coding, that control central metabolic pathways, cell death, proliferation,
differentiation, stress pathways, and mechanisms of drug resistance. Activation
of MYC has been widely reported in breast cancer progression. Breast cancer is a
complex heterogeneous disease and treatment options are primarily guided by
histological and biochemical evaluations of the tumors. Based on biochemical
markers, three main breast cancer categories are ER+ (estrogen receptor alpha
positive), HER2+ (human epidermal growth factor receptor 2 positive), and TNBC
(triple-negative breast cancer; estrogen receptor negative, progesterone receptor
negative, HER2 negative). MYC is elevated in TNBC compared with other cancer
subtypes. Interestingly, MYC-driven pathways are further elevated in aggressive
breast cancer cells and tumors that display drug resistant phenotype.
Identification of MYC target genes is essential in isolating signaling pathways
that drive tumor development. In this review, we address the role of MYC in the
three major breast cancer subtypes and highlight the most promising leads to
target MYC functions.
PMID- 28696358
TI - Traceability of On-Machine Tool Measurement: A Review.
AB - Nowadays, errors during the manufacturing process of high value components are
not acceptable in driving industries such as energy and transportation. Sectors
such as aerospace, automotive, shipbuilding, nuclear power, large science
facilities or wind power need complex and accurate components that demand close
measurements and fast feedback into their manufacturing processes. New measuring
technologies are already available in machine tools, including integrated touch
probes and fast interface capabilities. They provide the possibility to measure
the workpiece in-machine during or after its manufacture, maintaining the
original setup of the workpiece and avoiding the manufacturing process from being
interrupted to transport the workpiece to a measuring position. However, the
traceability of the measurement process on a machine tool is not ensured yet and
measurement data is still not fully reliable enough for process control or
product validation. The scientific objective is to determine the uncertainty on a
machine tool measurement and, therefore, convert it into a machine integrated
traceable measuring process. For that purpose, an error budget should consider
error sources such as the machine tools, components under measurement and the
interactions between both of them. This paper reviews all those uncertainty
sources, being mainly focused on those related to the machine tool, either on the
process of geometric error assessment of the machine or on the technology
employed to probe the measurand.
PMID- 28696359
TI - miRNAs in Normal and Malignant Hematopoiesis.
AB - Lineage specification is primarily regulated at the transcriptional level and
lineage-specific transcription factors determine cell fates. MicroRNAs (miRNAs)
are 18-24 nucleotide-long non-coding RNAs that post-transcriptionally decrease
the translation of target mRNAs and are essential for many cellular functions.
miRNAs also regulate lineage specification during hematopoiesis. This review
highlights the roles of miRNAs in B-cell development and malignancies, and
discusses how miRNA expression profiles correlate with disease prognoses and
phenotypes. We also discuss the potential for miRNAs as therapeutic targets and
diagnostic tools for B-cell malignancies.
PMID- 28696360
TI - Homogenate-assisted Vacuum-powered Bubble Extraction of Moso Bamboo Flavonoids
for On-line Scavenging Free Radical Capacity Analysis.
AB - A homogenate-assisted vacuum-powered bubble extraction (HVBE) method using
ethanol was applied for extraction of flavonoids from Phyllostachys pubescens (P.
pubescens) leaves. The mechanisms of homogenate-assisted extraction and vacuum
powered bubble generation were discussed in detail. Furthermore, a method for the
rapid determination of flavonoids by HPLC was established. HVBE followed by HPLC
was successfully applied for the extraction and quantification of four flavonoids
in P. pubescens, including orientin, isoorientin, vitexin, and isovitexin. This
method provides a fast and effective means for the preparation and determination
of plant active components. Moreover, the on-line antioxidant capacity, including
scavenging positive ion and negative ion free radical capacity of different
fractions from the bamboo flavonoid extract was evaluated. Results showed that
the scavenging DPPH free radical capacity of vitexin and isovitexin was larger
than that of isoorientin and orientin. On the contrary, the scavenging ABTS+free
radical capacity of isoorientin and orientin was larger than that of vitexin and
isovitexin.
PMID- 28696361
TI - Importance of Dietary Sources of Iron in Infants and Toddlers: Lessons from the
FITS Study.
AB - Iron deficiency (ID) affects 13.5% of 1-2 years old children in the US and may
have a negative impact on neurodevelopment and behavior. Iron-fortified infant
cereal is the primary non-heme iron source among infants aged 6-11.9 months. The
objective of this study was to compare iron intakes of infant cereal users with
non-users. Data from the Feeding Infants and Toddlers Study 2008 were used for
this analysis. Based on a 24-h recall, children between the ages of 4-17.9 months
were classified as 'cereal users' if they consumed any amount or type of infant
cereal and 'non-users' if they did not. Infant cereal was the top source of
dietary iron among infants aged 6-11.9 months. The majority of infants (74.6%)
aged 6-8.9 months consumed infant cereal, but this declined to 51.5% between 9
11.9 months and 14.8% among 12-17.9 months old toddlers. Infant cereal users
consumed significantly more iron than non-users across all age groups. Infants
and toddlers who consume infant cereal have higher iron intakes compared to non
users. Given the high prevalence of ID, the appropriate use of infant cereals in
a balanced diet should be encouraged to reduce the incidence of ID and ID anemia.
PMID- 28696362
TI - Trends of Adherence to the Mediterranean Dietary Pattern in Northern Italy from
2010 to 2016.
AB - Little information is available on the trends of adherence to the Mediterranean
dietary pattern (MDP). This study investigates food consumption trends from 2010
to 2016 in subjects living in Northern Italy. A cross-sectional study of 8584
subjects enrolled between January 2010 and December 2016 was conducted. Socio
demographic, nutrition and lifestyle characteristics were collected. A 14-item
questionnaire was used to evaluate adherence to MDP. Multivariable Poisson
regression was used to evaluate the trends of and the determinants for the
adherence to MDP. The overall prevalence of adherence to MDP was 14% and the
trend remained constant over the six years. However, there was a marked increase
in nuts consumption and a slight one in white meat consumption. Furthermore, we
observed a decrease in the consumption of fruit, red meat, sweets and sugar
sweetened beverages and in the use of soffritto. Finally, higher education, being
older, married, physically active, and ex-smoker was associated with greater
adherence to MDP, whereas the prevalence of adherence was lower in the obese. In
conclusion, the consumption of some Mediterranean and non-Mediterranean food
groups changed over the six years. However, overall, the prevalence of adherence
to MDP did not change. Additional strategies promoting healthy dietary habits are
needed.
PMID- 28696363
TI - Candle Soot Coating for Latent Fingermark Enhancement on Various Surfaces.
AB - We demonstrate a facile method termed candle soot coating (CSC) for fast
developing latent fingermarks (LFMs) on various kinds of surfaces (glass,
ceramic, metal, paper and adhesive tape). The CSC method can be considered as
simple, fast, and low-cost as well as providing high contrast for LFM
visualization in potential forensic applications.
PMID- 28696364
TI - The Influence of Maternal Dietary Patterns on Body Mass Index and Gestational
Weight Gain in Urban Black South African Women.
AB - Maternal pre-pregnancy body mass index (BMI) and subsequent gestational weight
gain (GWG) are strong predictors of maternal and infant outcomes; however the
influence of dietary patterns on BMI-specific GWG is unclear. This study
identifies patterns of habitual dietary intake in urban South African women and
explores their associations with first trimester BMI and GWG. Habitual dietary
intake of 538 pregnant women was assessed using a quantitative food-frequency
questionnaire and dietary patterns were depicted via principle component
analysis. Associations between dietary patterns and BMI-specific GWG were
analyzed using linear and logistic regression. Three dietary patterns were
identified: Western, Traditional and Mixed. Western and Mixed diet patterns were
associated with 35 g/week (p = 0.021) and 24 g/week (p = 0.041) higher GWG in
normal weight and obese women respectively. Additionally, high intakes of a
Traditional diet pattern were associated with a reduced odds of excessive weight
gain in the total sample (OR: 0.81; p = 0.006) and in normal weight women (OR:
0.68; p = 0.003). Increased intake of a traditional diet pattern-high in whole
grains, legumes, vegetables and traditional meats-and decreased intake of
refined, high sugar and fat driven diets may reduce GWG (including risk of
excessive weight gain) in urban South African women.
PMID- 28696365
TI - Synthesis and Evaluation of New Quinoxaline Derivatives of Dehydroabietic Acid as
Potential Antitumor Agents.
AB - A series of new quinoxaline derivatives of dehydroabietic acid (DAA) were
designed and synthesized as potential antitumor agents. Their structures were
characterized by IR, 1H-NMR, 13C-NMR, and MS spectra and elemental analyses. All
the new compounds were screened for their in vitro antiproliferative activities
against three human cancer cell lines (MCF-7, SMMC-7721 and HeLa) and
noncancerous human hepatocyte cells (LO2). A cytotoxic assay manifested that
compound 4b showed the most potent cytotoxic activity against the three cancer
cell lines, with IC50 values of 1.78 +/- 0.36, 0.72 +/- 0.09 and 1.08 +/- 0.12
MUM, respectively, and a substantially lower cytotoxicity to LO2 cells (IC50:
11.09 +/- 0.57 MUM). Moreover, the cell cycle analysis suggested that compound 4b
caused cell cycle arrest of SMMC-7721 cells at the G0/G1 phase. In a Hoechst
33258 staining assay, compound 4b caused considerable morphological changes of
the nuclei of SMMC-7721 cells, correlated with cell apoptosis. In addition, an
Annexin V-FITC/PI dual staining assay confirmed that compound 4b could induce the
apoptosis of SMMC-7721 cells in a dose-dependent manner.
PMID- 28696366
TI - Role and Therapeutic Targeting of the HGF/MET Pathway in Glioblastoma.
AB - Glioblastoma (GBM) is a lethal brain tumor with dismal prognosis. Current
therapeutic options, consisting of surgery, chemotherapy and radiation, have only
served to marginally increase patient survival. Receptor tyrosine kinases (RTKs)
are dysregulated in approximately 90% of GBM; attributed to this, research has
focused on inhibiting RTKs as a novel and effective therapy for GBM.
Overexpression of RTK mesenchymal epithelial transition (MET), and its ligand,
hepatocyte growth factor (HGF), in GBM highlights a promising new therapeutic
target. This review will discuss the role of MET in cell cycle regulation, cell
proliferation, evasion of apoptosis, cell migration and invasion, angiogenesis
and therapeutic resistance in GBM. It will also discuss the modes of deregulation
of HGF/MET and their regulation by microRNAs. As the HGF/MET pathway is a vital
regulator of multiple pro-survival pathways, efforts and strategies for its
exploitation for GBM therapy are also described.
PMID- 28696367
TI - The Evaluation of the Reactivating and Neuroprotective Efficacy of Two Newly
Prepared Bispyridinium Oximes (K305, K307) in Tabun-Poisoned Rats-A Comparison
with Trimedoxime and the Oxime K203.
AB - The ability of two newly developed oximes (K305, K307) to protect tabun-poisoned
rats from tabun-induced inhibition of brain acetylcholinesterase, acute
neurotoxic signs and symptoms and brain damage was compared with that of the
oxime K203 and trimedoxime. The reactivating and neuroprotective effects of the
oximes studied combined with atropine on rats poisoned with tabun at a sublethal
dose were evaluated. The reactivating efficacy of a newly developed oxime K305 is
lower compared to the reactivating efficacy of the oxime K203 and trimedoxime
while the ability of the oxime K307 to reactivate tabun-inhibited
acetylcholinesterase (AChE) in the brain roughly corresponds to the reactivating
efficacy of the oxime K203 and it is slightly lower compared to trimedoxime. In
addition, only one newly developed oxime (K307) combined with atropine was able
to markedly decrease tabun-induced neurotoxicity although it did not eliminate
all tabun-induced acute neurotoxic signs and symptoms. These results correspond
to the histopathological evaluation of tabun-induced brain damage. Therefore, the
newly developed oximes are not suitable for the replacement of commonly used
oximes (especially trimedoxime) in the treatment of acute tabun poisonings.
PMID- 28696368
TI - Clinical Applications of Autophagy Proteins in Cancer: From Potential Targets to
Biomarkers.
AB - Autophagy, a lysosome-mediated intracellular degradation and recycling pathway,
plays multiple context-dependent roles in tumorigenesis and treatment resistance.
Encouraging results from various preclinical studies have led to the initiation
of numerous clinical trials with the intention of targeting autophagy in various
cancers. Accumulating knowledge of the particular mechanisms and players involved
in different steps of autophagy regulation led to the ongoing discovery of small
molecule inhibitors designed to disrupt this highly orchestrated process.
However, the development of validated autophagy-related biomarkers, essential for
rational selection of patients entering clinical trials involving autophagy
inhibitors, is lagging behind. One possible source of biomarkers for this purpose
is the autophagy machinery itself. In this review, we address the recent trends,
challenges and advances in the assessment of the biomarker potential of
clinically relevant autophagy proteins in human cancers.
PMID- 28696369
TI - 2,5-Dihydroxyacetophenone Induces Apoptosis of Multiple Myeloma Cells by
Regulating the MAPK Activation Pathway.
AB - 2,5-Dihydroxyacetophenone (DHAP) is an active compound obtained from Radix
rehmanniae preparata, which is widely used as a herbal medicine in many Asian
countries. DHAP has been found to possess anti-inflammatory, anti-anxiety, and
neuroprotective qualities. For the present study, we evaluated the anti-cancer
effects of DHAP on multiple myeloma cells. It was discovered that DHAP
downregulated the expression of oncogenic gene products like Bcl-xl, Bcl-2, Mcl
1, Survivin, Cyclin D1, IAP-1, Cyclin E, COX-2, and MMP-9, and upregulated the
expression of Bax and p21 proteins, consistent with the induction of G2/M phase
cell cycle arrest and apoptosis in U266 cells. DHAP inhibited cell proliferation
and induced apoptosis, as characterized by the cleavage of PARP and the
activation of caspase-3, caspase-8, and caspase-9. Mitogen-activated protein
kinase (MAPK) pathways have been linked to the modulation of the angiogenesis,
proliferation, metastasis, and invasion of tumors. We therefore attempted to
determine the effect of DHAP on MAPK signaling pathways, and discovered that DHAP
treatment induced a sustained activation of JNK, ERK1/2, and p38 MAPKs. DHAP also
potentiated the pro-apoptotic and anti-proliferative effects of bortezomib in
U266 cells. Our results suggest that DHAP can be an effective therapeutic agent
to target multiple myeloma.
PMID- 28696370
TI - Strategies for Pathogen Biocontrol Using Lactic Acid Bacteria and Their
Metabolites: A Focus on Meat Ecosystems and Industrial Environments.
AB - The globalization of trade and lifestyle ensure that the factors responsible for
the emergence of diseases are more present than ever. Despite biotechnology
advancements, meat-based foods are still under scrutiny because of the presence
of pathogens, which causes a loss of consumer confidence and consequently a fall
in demand. In this context, Lactic Acid Bacteria (LAB) as GRAS organisms offer an
alternative for developing pathogen-free foods, particularly avoiding Listeria
monocytogenes, with minimal processing and fewer additives while maintaining the
foods' sensorial characteristics. The use of LAB strains, enabling us to produce
antimicrobial peptides (bacteriocins) in addition to lactic acid, with an impact
on quality and safety during fermentation, processing, and/or storage of meat and
ready-to-eat (RTE) meat products, constitutes a promising tool. A number of
bacteriocin-based strategies including the use of bioprotective cultures,
purified and/or semi-purified bacteriocins as well as their inclusion in varied
packaging materials under different storage conditions, have been investigated.
The application of bacteriocins as part of hurdle technology using non-thermal
technologies was explored for the preservation of RTE meat products. Likewise,
considering that food contamination with L. monocytogenes is a consequence of the
post-processing manipulation of RTE foods, the role of bacteriocinogenic LAB in
the control of biofilms formed on industrial surfaces is also discussed.
PMID- 28696371
TI - Biocompatibility of Four Common Orthopedic Biomaterials Following a High-Salt
Diet: An In Vivo Study.
AB - Nowadays, salt consumption appears to be drastically above the recommended level
in industrialized countries. The health consequences of this overconsumption are
heavy since high-salt intake induces cardiovascular disease, kidney dysfunction,
and stroke. Moreover, harmful interaction may also occur with orthopaedic devices
because overconsumption of salt reinforces the corrosive aspect of biological
tissues and favors bone resorption process. In the present study, we aimed to
assess the in vivo effect of three weeks of a high-salt diet, associated (or not)
with two weeks of the neuro-myoelectrostimulation (NMES) rehabilitation program
on the biocompatibility of four biomaterials used in the manufacture of
arthroplasty implants. Thus, two non-metallic (PEEK and Al2O3) and two metallic
(Ti6Al4V and CrCo) compounds were implanted in the rat tibial crest, and the
implant-to-bone adhesion and cell viability of two surrounded muscles, the Flexor
Digitorum (FD) and Tibialis Anterior (TA), were assessed at the end of the
experiment. Results indicated lower adhesion strength for the PEEK implant
compared to other biomaterials. An effect of NMES and a high-salt diet was only
identified for Al2O3 and Ti6Al4V implants, respectively. Moreover, compared to a
normal diet, a high-salt diet induced a higher number of dead cells on both
muscles for all biomaterials, which was further increased for PEEK, Al2O3, and
CrCo materials with NMES application. Finally, except for Ti6Al4V, NMES induced a
higher number of dead cells in the directly stimulated muscle (FD) compared to
the indirectly stimulated one (TA). This in vivo experiment highlights the
potential harmful effect of a high-salt diet for people who have undergone
arthroplasty, and a rehabilitation program based on NMES.
PMID- 28696372
TI - Warfarin and Flavonoids Do Not Share the Same Binding Region in Binding to the
IIA Subdomain of Human Serum Albumin.
AB - Human serum albumin (HSA) binds a variety of xenobiotics, including flavonoids
and warfarin. The binding of another ligand to the IIA binding site on HSA can
cause warfarin displacement and potentially the elevation of its free
concentration in blood. Studies dealing with flavonoid-induced warfarin
displacement from HSA provided controversial results: estimated risk of
displacement ranged from none to serious. To resolve these controversies, in
vitro study of simultaneous binding of warfarin and eight different flavonoid
aglycons and glycosides to HSA was carried out by fluorescence spectroscopy as
well as molecular docking. Results show that warfarin and flavonoids do not share
the same binding region in binding to HSA. Interactions were only observed at
high warfarin concentrations not attainable under recommended dosing regimes.
Docking experiments show that flavonoid aglycons and glycosides do not bind at
warfarin high affinity sites, but rather to different regions within the IIA HSA
subdomain. Thus, the risk of clinically significant warfarin-flavonoid
interaction in binding to HSA should be regarded as negligible.
PMID- 28696373
TI - Rehabilitation plus OnabotulinumtoxinA Improves Motor Function over
OnabotulinumtoxinA Alone in Post-Stroke Upper Limb Spasticity: A Single-Blind,
Randomized Trial.
AB - BACKGROUND: OnabotulinumtoxinA (BoNT-A) can temporarily decrease spasticity
following stroke, but whether there is an associated improvement in upper limb
function is less clear. This study measured the benefit of adding weekly
rehabilitation to a background of BoNT-A treatments for chronic upper limb
spasticity following stroke. METHODS: This was a multi-center clinical trial.
Thirty-one patients with post-stroke upper limb spasticity were treated with BoNT
A. They were then randomly assigned to 24 weeks of weekly upper limb
rehabilitation or no rehabilitation. They were injected up to two times, and
followed for 24 weeks. The primary outcome was change in the Fugl-Meyer upper
extremity score, which measures motor function, sensation, range of motion,
coordination, and speed. RESULTS: The 'rehab' group significantly improved on the
Fugl-Meyer upper extremity score (Visit 1 = 60, Visit 5 = 67) while the 'no
rehab' group did not improve (Visit 1 = 59, Visit 5 = 59; p = 0.006). This
improvement was largely driven by the upper extremity "movement" subscale, which
showed that the 'rehab' group was improving (Visit 1 = 33, Visit 5 = 37) while
the 'no rehab' group remained virtually unchanged (Visit 1 = 34, Visit 5 = 33; p
= 0.034). CONCLUSIONS: Following injection of BoNT-A, adding a program of
rehabilitation improved motor recovery compared to an injected group with no
rehabilitation.
PMID- 28696374
TI - Dissolution-Induced Nanowire Synthesis on Hot-Dip Galvanized Surface in
Supercritical Carbon Dioxide.
AB - In this study, we demonstrate a rapid treatment method for producing a needle
like nanowire structure on a hot-dip galvanized sheet at a temperature of 50
degrees C. The processing method involved only supercritical carbon dioxide and
water to induce a reaction on the zinc surface, which resulted in growth of zinc
hydroxycarbonate nanowires into flower-like shapes. This artificial patina
nanostructure predicts high surface area and offers interesting opportunities for
its use in industrial high-end applications. The nanowires can significantly
improve paint adhesion and promote electrochemical stability for organic
coatings, or be converted to ZnO nanostructures by calcining to be used in
various semiconductor applications.
PMID- 28696375
TI - Is the Grass Always Greener in Suburban Neighborhoods? Outdoors Play in Suburban
and Inner-City Neighborhoods.
AB - Children's outdoors play (OP) is an important source of physical activity that
has been decreasing in recent years due to changes in neighborhood design, parent
safety concerns and child sedentary leisure. However, few studies examined such
determinants from children's perspectives. This study explores environmental and
socio-cultural aspects of children's OP using a qualitative and quantitative
approach. Data was collected in two phases: (1) a survey on OP and related
variables among 5th and 6th graders (10-12 years old) (n = 573); and (2) a
mapping activity and semi-structured interview among a subsample of the survey (n
= 80). The most common locations for routine OP were parks (40%) followed by
public facilities (26%) and streets (17%). OP was significantly associated with
perceived environment, independent mobility and gender, but not with neighborhood
type. Inner-city participants reported a higher number and greater variety of OP
areas (23 vs. 14). Three main barriers of OP were identified-low quality and
poorly maintained play areas, other people in public spaces, and social norms
that undermine OP. Thus, in order to encourage routine OP, environmental change
to create safe and attractive OP settings should be accompanied by community
interventions to enhance social norms that are supportive of OP.
PMID- 28696377
TI - Task Assignment and Path Planning for Multiple Autonomous Underwater Vehicles
Using 3D Dubins Curves ?.
AB - This paper investigates the task assignment and path planning problem for
multiple AUVs in three dimensional (3D) underwater wireless sensor networks where
nonholonomic motion constraints of underwater AUVs in 3D space are considered.
The multi-target task assignment and path planning problem is modeled by the
Multiple Traveling Sales Person (MTSP) problem and the Genetic Algorithm (GA) is
used to solve the MTSP problem with Euclidean distance as the cost function and
the Tour Hop Balance (THB) or Tour Length Balance (TLB) constraints as the stop
criterion. The resulting tour sequences are mapped to 2D Dubins curves in the X -
Y plane, and then interpolated linearly to obtain the Z coordinates. We
demonstrate that the linear interpolation fails to achieve G 1 continuity in the
3D Dubins path for multiple targets. Therefore, the interpolated 3D Dubins curves
are checked against the AUV dynamics constraint and the ones satisfying the
constraint are accepted to finalize the 3D Dubins curve selection. Simulation
results demonstrate that the integration of the 3D Dubins curve with the MTSP
model is successful and effective for solving the 3D target assignment and path
planning problem.
PMID- 28696376
TI - Lack of Additive Effects of Resveratrol and Energy Restriction in the Treatment
of Hepatic Steatosis in Rats.
AB - The aims of the present study were to analyze the effect of resveratrol on liver
steatosis in obese rats, to compare the effects induced by resveratrol and energy
restriction and to research potential additive effects. Rats were initially fed a
high-fat high-sucrose diet for six weeks and then allocated in four experimental
groups fed a standard diet: a control group, a resveratrol-treated group, an
energy restricted group and a group submitted to energy restriction and treated
with resveratrol. We measured liver triacylglycerols, transaminases, FAS, MTP,
CPT1a, CS, COX, SDH and ATP synthase activities, FATP2/FATP5, DGAT2, PPARalpha,
SIRT1, UCP2 protein expressions, ACC and AMPK phosphorylation and PGC1alpha
deacetylation. Resveratrol reduced triacylglycerols compared with the controls,
although this reduction was lower than that induced by energy restriction. The
mechanisms of action were different. Both decreased protein expression of fatty
acid transporters, thus suggesting reduced fatty acid uptake from blood stream
and liver triacylglycerol delivery, but only energy restriction reduced the
assembly. These results show that resveratrol is useful for liver steatosis
treatment within a balanced diet, although its effectiveness is lower than that
of energy restriction. However, resveratrol is unable to increase the reduction
in triacylglycerol content induced by energy restriction.
PMID- 28696378
TI - Rapid ELISA Using a Film-Stack Reaction Field with Micropillar Arrays.
AB - A film-stack reaction field with a micropillar array using a motor stirrer was
developed for the high sensitivity and rapid enzyme-linked immunosorbent assay
(ELISA) reaction. The effects of the incubation time of a protein (30 s, 5 min,
and 10 min) on the fluorescence intensity in ELISAs were investigated using a
reaction field with different micropillar array dimensions (5-um, 10-um and 50-um
gaps between the micropillars). The difference in fluorescence intensity between
the well with the reaction field of 50-um gap for the incubation time of 30 s and
the well without the reaction field with for incubation time of 10 min was 6%.
The trend of the fluorescence intensity in the gap between the micro pillars in
the film-stack reaction field was different between the short incubation time and
the long incubation time. The theoretical analysis of the physical parameters
related with the biomolecule transport indicated that the reaction efficiency
defined in this study was the dominant factor determining the fluorescence
intensity for the short incubation time, whereas the volumetric rate of the
circulating flow through the space between films and the specific surface area
were the dominant factors for the long incubation time.
PMID- 28696379
TI - Obesity and Asthma: A Missing Link.
AB - Obesity and asthma are two chronic conditions that affect millions of people.
Genetic and lifestyle factors such as diet, physical activity, and early exposure
to micro-organisms are important factors that may contribute to the escalating
prevalence of both conditions. The prevalence of asthma is higher in obese
individuals. Recently, two major phenotypes of asthma with obesity have been
described: one phenotype of early-onset asthma that is aggravated by obesity, and
a second phenotype of later-onset asthma that predominantly affects women.
Systemic inflammation and mechanical effect, both due to the expansion of the
adipose tissue, have been proposed as the main reasons for the association
between obesity and asthma. However, the mechanisms involved are not yet fully
understood. Moreover, it has also been suggested that insulin resistance syndrome
can have a role in the association between these conditions. The intestinal
microbiota is an important factor in the development of the immune system, and
can be considered a link between obesity and asthma. In the obese state, higher
lipopolysaccharide (LPS) serum levels as a consequence of a microbiota dysbiosis
have been found. In addition, changes in microbiota composition result in a
modification of carbohydrate fermentation capacity, therefore modifying short
chain fatty acid (SCFA) levels. The main objective of this review is to summarize
the principal findings that link obesity and asthma.
PMID- 28696380
TI - Whey Protein Supplementation Enhances Whole Body Protein Metabolism and
Performance Recovery after Resistance Exercise: A Double-Blind Crossover Study.
AB - No study has concurrently measured changes in free-living whole body protein
metabolism and exercise performance during recovery from an acute bout of
resistance exercise. We aimed to determine if whey protein ingestion enhances
whole body net protein balance and recovery of exercise performance during
overnight (10 h) and 24 h recovery after whole body resistance exercise in
trained men. In a double-blind crossover design, 12 trained men (76 +/- 8 kg, 24
+/- 4 years old, 14% +/- 5% body fat; means +/- standard deviation (SD))
performed resistance exercise in the evening prior to consuming either 25 g of
whey protein (PRO; MuscleTech 100% Whey) or an energy-matched placebo (CHO)
immediately post-exercise (0 h), and again the following morning (~10 h of
recovery). A third randomized trial, completed by the same participants,
involving no exercise and no supplement served as a rested control trial (Rest).
Participants ingested [15N]glycine to determine whole body protein kinetics and
net protein balance over 10 and 24 h of recovery. Performance was assessed pre
exercise and at 0, 10, and 24 h of recovery using a battery of tests. Net protein
balance tended to improve in PRO (P = 0.064; effect size (ES) = 0.61, PRO vs.
CHO) during overnight recovery. Over 24 h, net balance was enhanced in PRO (P =
0.036) but not in CHO (P = 0.84; ES = 0.69, PRO vs. CHO), which was mediated
primarily by a reduction in protein breakdown (PRO < CHO; P < 0.01. Exercise
decreased repetitions to failure (REP), maximal strength (MVC), peak and mean
power, and countermovement jump performance (CMJ) at 0 h (all P < 0.05 vs. Pre).
At 10 h, there were small-to-moderate effects for enhanced recovery of the MVC
(ES = 0.56), mean power (ES = 0.49), and CMJ variables (ES: 0.27-0.49) in PRO. At
24 h, protein supplementation improved MVC (ES = 0.76), REP (ES = 0.44), and peak
power (ES = 0.55). In conclusion, whey protein supplementation enhances whole
body anabolism, and may improve acute recovery of exercise performance after a
strenuous bout of resistance exercise.
PMID- 28696381
TI - Cost Saving Opportunities in NSCLC Therapy by Optimized Diagnostics.
AB - With an incidence of 68 new cases per 100,000 people per year, an estimated total
number of up to 350,000 new non-small-cell lung cancer (NSCLC) cases are
diagnosed each year in the European Union. Up to 10% of NSCLC patients are
eligible for therapy with novel ALK (anaplastic lymphoma kinase) inhibitors, as
they have been diagnosed with a mutation in the gene coding for ALK. The ALK
inhibitor therapy costs add up to approx. 9,000 ? per patient per month, with
treatment durations of up to one year. Recent studies have shown that up to 10%
of ALK cases are misdiagnosed by nearly 40% of pathologic investigations. The
current state-of-the-art ALK diagnostic procedure comprises a Fluorescent in situ
Hybridization (FISH) assay accompanied by ALK inhibitor therapy (Crizotinib). The
therapy success ranges between a full therapy failure and the complete remission
of the tumor (i.e., healing), but the biomedical and systemic reasons for this
range remain unknown so far. It appears that the variety of different ALK
mutations and variants contributes to the discrepancy in therapy results.
Although the major known fusion partner for ALK in NSCLC is the Echinoderm
microtubule-associated protein-like 4 (EML4), of which a minimum of 15 variants
have been described, an additional 20 further ALK fusion variants with other
genes are known, of which three have already been found in NSCLC. We hypothesize
that the wide variety of known (and unknown) ALK mutations is associated with a
variable therapy success, thus rendering current companion diagnostic procedures
(FISH) and therapy (Crizotinib) only partly applicable in ALK-related NSCLC
treatment. In cell culture, differing sensitivity to Crizotinib has been shown
for some fusion variants, but it is as yet unknown which of them are really
biologically active in cancer patients, and how the respective variants affect
the response to Crizotinib treatment. Moreover, it has been demonstrated that
translocated ALK genes can also be observed in healthy tissues and are not
compulsorily associated with tumors. Therefore, it is important to keep in mind
that even for the known variants of ALK fusion genes, the biological function is
not known for all variants, and that no information is available on the
homogeneity of ALK fusion variants within a single tumor. These facts, in concert
with data for ALK mutation prevalence and therapy outcomes of a German cohort of
NSCLC patients, support the hypothesis that, by using novel companion diagnostic
tools in combination with therapy outcome predictions, massive cost savings could
be possible in European Health Care systems without a loss of patient care.
PMID- 28696383
TI - Alfalfa Responses to Gypsum Application Measured Using Undisturbed Soil Columns.
AB - Gypsum is an excellent source of Ca and S, both of which are required for crop
growth. Large amounts of by-product gypsum [Flue gas desulfurization gypsum
(FGDG)] are produced from coal combustion in the United States, but only 4% is
used for agricultural purposes. The objective of this study was to evaluate the
effects of (1) untreated, (2) short-term (4-year annual applications of gypsum
totaling 6720 kg ha-1), and (3) long-term (12-year annual applications of gypsum
totaling 20,200 kg ha-1) on alfalfa (Medicago sativa L.) growth and nutrient
uptake, and gypsum movement through soil. The study was conducted in a greenhouse
using undisturbed soil columns of two non-sodic soils (Celina silt loam and
Brookston loam). Aboveground growth of alfalfa was not affected by gypsum
treatments when compared with untreated (p > 0.05). Total root biomass (0-75 cm)
for both soils series was significantly increased by gypsum application (p =
0.04), however, increased root growth was restricted to 0-10 cm depth. Soil and
plant analyses indicated no unfavorable environmental impact from of the 4-year
and 12-year annual application of FGDG. We concluded that under sufficient water
supply, by-product gypsum is a viable source of Ca and S for land application
that might benefit alfalfa root growth, but has less effect on aboveground
alfalfa biomass production. Undisturbed soil columns were a useful adaptation of
the lysimeter method that allowed detailed measurements of alfalfa nutrient
uptake, root biomass, and yield and nutrient movement in soil.
PMID- 28696382
TI - Phosphoinositide 3-Kinase-Dependent Signalling Pathways in Cutaneous Squamous
Cell Carcinomas.
AB - Cutaneous squamous cell carcinoma (cSCC) derives from keratinocytes in the
epidermis and accounts for 15-20% of all cutaneous malignancies. Although it is
usually curable by surgery, 5% of these tumours metastasise leading to poor
prognosis mostly because of a lack of therapies and validated biomarkers. As the
incidence rate is rising worldwide it has become increasingly important to better
understand the mechanisms involved in cSCC development and progression in order
to develop therapeutic strategies. Here we discuss some of the evidence
indicating that activation of phosphoinositide 3-kinases (PI3Ks)-dependent
signalling pathways (in particular the PI3Ks targets Akt and mTOR) has a key role
in cSCC. We further discuss available data suggesting that inhibition of these
pathways can be beneficial to counteract the disease. With the growing number of
different inhibitors currently available, it would be important to further
investigate the specific contribution of distinct components of the
PI3Ks/Akt/mTOR pathways in order to identify the most promising molecular targets
and the best strategy to inhibit cSCC.
PMID- 28696384
TI - Physical and Emotional Benefits of Different Exercise Environments Designed for
Treadmill Running.
AB - (1) Background: Green physical activity promotes physical health and mental
wellbeing and interesting questions concern effects of this information on
designing indoor exercise environments. This study examined the physical and
emotional effects of different nature-based environments designed for indoor
treadmill running; (2) Methods: In a counterbalanced experimental design, 30
participants performed three, twenty-minute treadmill runs at a self-selected
pace while viewing either a static nature image, a dynamic nature image or self
selected entertainment. Distance ran, heart rate (HR) and five pre-and post
exercise emotional states were measured; (3) Results: Participants ran farther,
and with higher HRs, with self-selected entertainment compared to the two nature
based environment designs. Participants attained lowered anger, dejection,
anxiety and increased excitement post exercise in all of the designed
environments. Happiness increased during the two nature-based environment designs
compared with self-selected entertainment; (4) Conclusions: Self-selected
entertainment encouraged greater physical performances whereas running in nature
based exercise environments elicited greater happiness immediately after running.
PMID- 28696385
TI - Body Shape and Weight Loss as Motivators for Breastfeeding Initiation and
Continuation.
AB - Breastfeeding rates in the UK are low. Efforts to promote breastfeeding typically
include the known health benefits for mother and child, many of which are not
immediate. Gaining immediate benefits can be effective motivators of behaviour.
Body-related changes resulting from breastfeeding could be an immediate benefit.
This study explored breastfeeding mothers' reports of body-related changes as
benefits of breastfeeding. Mothers (N = 182) who currently, or had recently,
breastfed an infant completed a survey detailing their infant feeding choices and
the perceived benefits of breastfeeding on their bodies. Half of the mothers felt
that breastfeeding had a positive effect on their body. Benefits were grouped
into five themes: (1) Returning to pre-pregnancy body shape; (2) Health benefits;
(3) Physical benefits; (4) Eating benefits; (5) Psychological benefits. These
themes highlight the numerous body-related benefits that mothers identified as
resulting from breastfeeding and suggest that immediate, personal, and appearance
related gains of breastfeeding are highly valued. These findings indicate that
interventions would likely benefit from emphasising the more immediate physical
and psychological benefits of breastfeeding, alongside the health and bonding
benefits, as a way to promote breastfeeding initiation and continuation in more
women. This may be particularly effective for groups such as young mothers, where
breastfeeding rates are low and whose emphasis on body image may be greater.
PMID- 28696386
TI - Analytic and Diagnostic Performances of Human Papillomavirus E6/E7 mRNA Test on
up-to 11-Year-Old Liquid-Based Cervical Samples. A Biobank-Based Longitudinal
Study.
AB - Human Papillomavirus (HPV) E6/E7 mRNA test demonstrated high specificity in
detecting HPV infections, but studies assessing its efficacy in terms of cancer
risk stratification are lacking. Follow-up studies are arduous and expensive.
Biobank would be the answer to the problem, although data investigating the
effects of long-term storage on RNA preservation are still needed. We addressed
these issues by retrieving 202 residual liquid-based cervical specimens,
collected from 149 women attending cervical cancer screening during the years
2001-2012. Samples were stored in Adriatic Biobank at room temperature and
without any handing. After calculation of RNA yield and purity, E6/E7 mRNA test
was retrospectively performed on each samples, to assess analytic and diagnostic
performances. Using automated extraction procedures, RNA of good quantity and
quality was obtained. The mean value of RNA concentration was 27.5 ng/MUL. The
mean A260/A280 ratio was 2.1. An invalid mRNA test result was found in 11.9% of
the specimens. Neither RNA integrity, nor analytic performances of mRNA test were
influenced by the year of sample collection. In total, 62.4% of the specimens
tested as mRNA positive; among these, 89.2% were CIN2+. E6/E7 mRNA was detected
in all Squamous Cervical Cancer (SCC) cases. Percentage of positive samples
increased with the severity of histological diagnosis. mRNA testing, showing
specificity and predictive values of 75.6% and 84.4%, respectively, significantly
improved the corresponding values for DNA testing. Thus, the reflex mRNA test was
demonstrated to be suitable to triage women with persistent cervical lesions. A
"one sample for all" approach is possible, with practical benefits for Biobank
based long-term longitudinal studies, diseases prevention, prediction, diagnosis
and treatment.
PMID- 28696387
TI - Evaluating Childhood Vaccination Coverage of NIP Vaccines: Coverage Survey versus
Zhejiang Provincial Immunization Information System.
AB - Vaccination coverage in Zhejiang province, east China, is evaluated through
repeated coverage surveys. The Zhejiang provincial immunization information
system (ZJIIS) was established in 2004 with links to all immunization clinics.
ZJIIS has become an alternative to quickly assess the vaccination coverage. To
assess the current completeness and accuracy on the vaccination coverage derived
from ZJIIS, we compared the estimates from ZJIIS with the estimates from the most
recent provincial coverage survey in 2014, which combined interview data with
verified data from ZJIIS. Of the enrolled 2772 children in the 2014 provincial
survey, the proportions of children with vaccination cards and registered in
ZJIIS were 94.0% and 87.4%, respectively. Coverage estimates from ZJIIS were
systematically higher than the corresponding estimates obtained through the
survey, with a mean difference of 4.5%. Of the vaccination doses registered in
ZJIIS, 16.7% differed from the date recorded in the corresponding vaccination
cards. Under-registration in ZJIIS significantly influenced the coverage
estimates derived from ZJIIS. Therefore, periodic coverage surveys currently
provide more complete and reliable results than the estimates based on ZJIIS
alone. However, further improvement of completeness and accuracy of ZJIIS will
likely allow more reliable and timely estimates in future.
PMID- 28696388
TI - Positive Emotional Effects of Leisure in Green Spaces in Alleviating Work-Family
Spillover in Working Mothers.
AB - Studies have shown that family and work spillover affects well-being and that
leisure activities can alleviate the negative effects of work-related stress on
health. However, few studies have focused on investigating the effects of
specific leisure activities among specific populations. To examine whether
leisure activities in green spaces can promote individual recovery processes and
alleviate the effects of work and family spillover on positive emotions, this
study applied the effort-recovery model to a population of working mothers.
Through online and paper questionnaires, sample data were collected from 221
working mothers in Taiwan. Structural equation modeling was used to test the
experimental hypothesis, and mediation analysis was used to determine whether
leisure in green spaces is a mediating factor. The results indicated that leisure
in green spaces is a mediator of the relationship of negative work and family
spillover with positive emotions. In addition, strolls and park visits were found
to provide greater psychological benefits to working mothers, compared with
picnics.
PMID- 28696389
TI - Strategies to Improve Adherence to Dietary Weight Loss Interventions in Research
and Real-World Settings.
AB - Dietary interventions are the cornerstone of obesity treatment. The optimal
dietary approach to weight loss is a hotly debated topic among health
professionals and the lay public alike. An emerging body of evidence suggests
that a higher level of adherence to a diet, regardless of the type of diet, is an
important factor in weight loss success over the short and long term. Key
strategies to improve adherence include designing dietary weight loss
interventions (such as ketogenic diets) that help to control the increased drive
to eat that accompanies weight loss, tailoring dietary interventions to a
person's dietary preferences (and nutritional requirements), and promoting self
monitoring of food intake. The aim of this paper is to examine these strategies,
which can be used to improve adherence and thereby increase the success of
dietary weight loss interventions.
PMID- 28696390
TI - Secure and Time-Aware Communication of Wireless Sensors Monitoring Overhead
Transmission Lines.
AB - Existing transmission power grids suffer from high maintenance costs and
scalability issues along with a lack of effective and secure system monitoring.
To address these problems, we propose to use Wireless Sensor Networks (WSNs) as a
technology to achieve energy efficient, reliable, and low-cost remote monitoring
of transmission grids. With WSNs, smart grid enables both utilities and customers
to monitor, predict and manage energy usage effectively and react to possible
power grid disturbances in a timely manner. However, the increased application of
WSNs also introduces new security challenges, especially related to privacy,
connectivity, and security management, repeatedly causing unpredicted
expenditures. Monitoring the status of the power system, a large amount of
sensors generates massive amount of sensitive data. In order to build an
effective Wireless Sensor Network (WSN) for a smart grid, we focus on designing a
methodology of efficient and secure delivery of the data measured on transmission
lines. We perform a set of simulations, in which we examine different routing
algorithms, security mechanisms and WSN deployments in order to select the
parameters that will not affect the delivery time but fulfill their role and
ensure security at the same time. Furthermore, we analyze the optimal placement
of direct wireless links, aiming at minimizing time delays, balancing network
performance and decreasing deployment costs.
PMID- 28696391
TI - Site-Specific PEGylated Adeno-Associated Viruses with Increased Serum Stability
and Reduced Immunogenicity.
AB - Adeno-associated virus (AAV) is one of the most extensively studied and utilized
viral vectors in clinical gene transfer research. However, the serum instability
and immunogenicity of AAV vectors significantly limit their application. Here, we
endeavored to overcome these limitations by developing a straightforward approach
for site-specific PEGylation of AAV via genetic code expansion. This technique
includes incorporation of the azide moiety into the AAV capsid protein followed
by orthogonal and stoichiometric conjugation of a variety of polyethylene glycols
(PEGs) through click chemistry. Using this approach, only the chosen site(s) was
consistently PEGylated under mild conditions, preventing nonselective
conjugation. Upon a series of in vitro examinations, AAVs conjugated with 20-kD
PEG at sites Q325+1, S452+1, and R585+1 showed a 1.7- to 2.4-fold stability
improvement in pooled human serum and a nearly twofold reduction in antibody
recognition. Subsequent animal research on Sprague Dawley rats displayed a
promising 20% reduction in antibody inducement and a higher virus titer in the
blood. Together, our data demonstrate successful protection of an AAV vector from
antibody neutralization and blood clearance, thereby increasing the efficiency of
therapeutic gene delivery.
PMID- 28696392
TI - Comparative Transcriptome Analysis Reveals Adaptive Evolution of Notopterygium
incisum and Notopterygium franchetii, Two High-Alpine Herbal Species Endemic to
China.
AB - The extreme conditions (e.g., cold, low oxygen, and strong ultraviolet radiation)
of the high mountains provide an ideal natural laboratory for studies on
speciation and the adaptive evolution of organisms. Up to now, few
genome/transcriptome-based studies have been carried out on how plants adapt to
conditions at extremely high altitudes. Notopterygium incisum and Notopterygium
franchetii (Notopterygium, Apiaceae) are two endangered high-alpine herbal plants
endemic to China. To explore the molecular genetic mechanisms of adaptation to
high altitudes, we performed high-throughput RNA sequencing (RNA-seq) to
characterize the transcriptomes of the two species. In total, more than 130
million sequence reads, 81,446 and 63,153 unigenes with total lengths of
86,924,837 and 62,615,693 bp, were generated for the two herbal species,
respectively. OrthoMCL analysis identified 6375 single-copy orthologous genes
between N. incisum and N. franchetii. In total, 381 positively-selected candidate
genes were identified for both plants by using estimations of the non-synonymous
to synonymous substitution rate. At least 18 of these genes potentially
participate in RNA splicing, DNA repair, glutathione metabolism and the plant
pathogen interaction pathway, which were further enriched in various functional
gene categories possibly responsible for environment adaptation in high
mountains. Meanwhile, we detected various transcription factors that regulated
the material and energy metabolism in N. incisum and N. franchetii, which
probably play vital roles in the tolerance to stress in surroundings. In
addition, 60 primer pairs based on orthologous microsatellite-containing
sequences between the both Notopterygium species were determined. Finally, 17
polymorphic microsatellite markers (SSR) were successfully characterized for the
two endangered species. Based on these candidate orthologous and SSR markers, we
detected that the adaptive evolution and species divergence of N. incisum and N.
franchetii were significantly associated with the extremely heterogeneous
environments and climatic oscillations in high-altitude areas. This work provides
important insights into the molecular mechanisms of adaptation to high-altitudes
in alpine herbal plants.
PMID- 28696393
TI - Secure Service Proxy: A CoAP(s) Intermediary for a Securer and Smarter Web of
Things.
AB - As the IoT continues to grow over the coming years, resource-constrained devices
and networks will see an increase in traffic as everything is connected in an
open Web of Things. The performance- and function-enhancing features are
difficult to provide in resource-constrained environments, but will gain
importance if the WoT is to be scaled up successfully. For example, scalable open
standards-based authentication and authorization will be important to manage
access to the limited resources of constrained devices and networks.
Additionally, features such as caching and virtualization may help further reduce
the load on these constrained systems. This work presents the Secure Service
Proxy (SSP): a constrained-network edge proxy with the goal of improving the
performance and functionality of constrained RESTful environments. Our
evaluations show that the proposed design reaches its goal by reducing the load
on constrained devices while implementing a wide range of features as different
adapters. Specifically, the results show that the SSP leads to significant
savings in processing, network traffic, network delay and packet loss rates for
constrained devices. As a result, the SSP helps to guarantee the proper operation
of constrained networks as these networks form an ever-expanding Web of Things.
PMID- 28696394
TI - Influence of Genetic Variations in Selenoprotein Genes on the Pattern of Gene
Expression after Supplementation with Brazil Nuts.
AB - Selenium (Se) is an essential micronutrient for human health. Its beneficial
effects are exerted by selenoproteins, which can be quantified in blood and used
as molecular biomarkers of Se status. We hypothesize that the presence of genetic
polymorphisms in selenoprotein genes may: (1) influence the gene expression of
specific selenoproteins and (2) influence the pattern of global gene expression
after Brazil nut supplementation. The study was conducted with 130 healthy
volunteers in Sao Paulo, Brazil, who consumed one Brazil nut (300 MUg/Se) a day
for eight weeks. Gene expression of GPX1 and SELENOP and genotyping were measured
by real-time PCR using TaqMan Assays. Global gene expression was assessed by
microarray using Illumina HumanHT-12 v4 BeadChips. Brazil nut supplementation
significantly increased GPX1 mRNA expression only in subjects with CC genotype at
rs1050450 (p < 0.05). SELENOP mRNA expression was significantly higher in A
carriers at rs7579 either before or after supplementation (p < 0.05). Genotype
for rs713041 in GPX4 affected the pattern of blood cell global gene expression.
Genetic variations in selenoprotein genes modulated both GPX1 and SELENOP
selenoprotein gene expression and global gene expression in response to Brazil
nut supplementation.
PMID- 28696395
TI - A Fine-Grained and Privacy-Preserving Query Scheme for Fog Computing-Enhanced
Location-Based Service.
AB - Location-based services (LBS), as one of the most popular location-awareness
applications, has been further developed to achieve low-latency with the
assistance of fog computing. However, privacy issues remain a research challenge
in the context of fog computing. Therefore, in this paper, we present a fine
grained and privacy-preserving query scheme for fog computing-enhanced location
based services, hereafter referred to as FGPQ. In particular, mobile users can
obtain the fine-grained searching result satisfying not only the given spatial
range but also the searching content. Detailed privacy analysis shows that our
proposed scheme indeed achieves the privacy preservation for the LBS provider and
mobile users. In addition, extensive performance analyses and experiments
demonstrate that the FGPQ scheme can significantly reduce computational and
communication overheads and ensure the low-latency, which outperforms existing
state-of-the art schemes. Hence, our proposed scheme is more suitable for real
time LBS searching.
PMID- 28696396
TI - The Interaction between Nidovirales and Autophagy Components.
AB - Autophagy is a conserved intracellular catabolic pathway that allows cells to
maintain homeostasis through the degradation of deleterious components via
specialized double-membrane vesicles called autophagosomes. During the past
decades, it has been revealed that numerous pathogens, including viruses, usurp
autophagy in order to promote their propagation. Nidovirales are an order of
enveloped viruses with large single-stranded positive RNA genomes. Four virus
families (Arterividae, Coronaviridae, Mesoniviridae, and Roniviridae) are part of
this order, which comprises several human and animal pathogens of medical and
veterinary importance. In host cells, Nidovirales induce membrane rearrangements
including autophagosome formation. The relevance and putative mechanism of
autophagy usurpation, however, remain largely elusive. Here, we review the
current knowledge about the possible interplay between Nidovirales and autophagy.
PMID- 28696397
TI - Characterization and Biological Evaluation of Propolis from Poland.
AB - In this study, we assessed the therapeutic potential of propolis from Poland and
performed chemical analysis by GC-MS, as well as determined its botanical origin.
Chemical constituents typical for bud exudates of Populusnigra (section Aigeiros)
were determined, however, glycerol esters of phenolic acids, as well as unusually
high amounts of p-coumaric and ferulic acid and their benzyl esters, were also
detected. These constituents are characteristic for buds of Populustremula
(section Leuce). We also evaluated the antiproliferative effect of propolis
extracts against nine human cancer cell lines. Additionally, promising
antibacterial activity of the dichloromethane extract (Minimal Inhibitory
Concentration MIC values of 0.95-1.24 mg/mL), as well as a moderate antifungal
activity (MIC values of 1.25-1.40 mg/mL), was noticed. Propolis from Poland
appeared as a rich source of antibacterial and antiproliferative compounds and
this confirmed that it is a valuable natural product with the potential to
improve human health.
PMID- 28696398
TI - Maitotoxin-4, a Novel MTX Analog Produced by Gambierdiscus excentricus.
AB - Maitotoxins (MTXs) are among the most potent toxins known. These toxins are
produced by epi-benthic dinoflagellates of the genera Gambierdiscus and Fukuyoa
and may play a role in causing the symptoms associated with Ciguatera Fish
Poisoning. A recent survey revealed that, of the species tested, the newly
described species from the Canary Islands, G. excentricus, is one of the most
maitotoxic. The goal of the present study was to characterize MTX-related
compounds produced by this species. Initially, lysates of cells from two Canary
Island G. excentricus strains VGO791 and VGO792 were partially purified by (i)
liquid-liquid partitioning between dichloromethane and aqueous methanol followed
by (ii) size-exclusion chromatography. Fractions from chromatographic separation
were screened for MTX toxicity using both the neuroblastoma neuro-2a (N2a)
cytotoxicity and Ca2+ flux functional assays. Fractions containing MTX activity
were analyzed using liquid chromatography coupled to high-resolution mass
spectrometry (LC-HRMS) to pinpoint potential MTX analogs. Subsequent non-targeted
HRMS analysis permitted the identification of a novel MTX analog, maitotoxin-4
(MTX4, accurate mono-isotopic mass of 3292.4860 Da, as free acid form) in the
most toxic fractions. HRMS/MS spectra of MTX4 as well as of MTX are presented. In
addition, crude methanolic extracts of five other strains of G. excentricus and
37 other strains representing one Fukuyoa species and ten species, one ribotype
and one undetermined strain/species of Gambierdiscus were screened for the
presence of MTXs using low resolution tandem mass spectrometry (LRMS/MS). This
targeted analysis indicated the original maitotoxin (MTX) was only present in one
strain (G. australes S080911_1). Putative maitotoxin-2 (p-MTX2) and maitotoxin-3
(p-MTX3) were identified in several other species, but confirmation was not
possible because of the lack of reference material. Maitotoxin-4 was detected in
all seven strains of G. excentricus examined, independently of their origin
(Brazil, Canary Islands and Caribbean), and not detected in any other species.
MTX4 may therefore serve as a biomarker for the highly toxic G. excentricus in
the Atlantic area.
PMID- 28696399
TI - Dendritic Cells and Their Role in Allergy: Uptake, Proteolytic Processing and
Presentation of Allergens.
AB - Dendritic cells (DCs) are the most important antigen presenting cells to activate
naive T cells, which results in the case of Type 1 allergies in a Type 2 helper T
cell (Th2)-driven specific immune response towards allergens. So far, a number of
different subsets of specialized DCs in different organs have been identified. In
the recent past methods to study the interaction of DCs with allergenic proteins,
their different uptake and processing mechanisms followed by the presentation to
T cells were developed. The following review aims to summarize the most important
characteristics of DC subsets in the context of allergic diseases, and highlights
the recent findings. These detailed studies can contribute to a better
understanding of the pathomechanisms of allergic diseases and contribute to the
identification of key factors to be addressed for therapeutic interventions.
PMID- 28696400
TI - The Epiphytic Genus Gambierdiscus (Dinophyceae) in the Kermadec Islands and
Zealandia Regions of the Southwestern Pacific and the Associated Risk of
Ciguatera Fish Poisoning.
AB - Species in the genus Gambierdiscus produce ciguatoxins (CTXs) and/or maitotoxins
(MTXs), which may cause ciguatera fish poisoning (CFP) in humans if contaminated
fish are consumed. Species of Gambierdiscus have previously been isolated from
macroalgae at Rangitahua (Raoul Island and North Meyer Islands, northern Kermadec
Islands), and the opportunity was taken to sample for Gambierdiscus at the more
southerly Macauley Island during an expedition in 2016. Gambierdiscus cells were
isolated, cultured, and DNA extracted and sequenced to determine the species
present. Bulk cultures were tested for CTXs and MTXs by liquid chromatography
mass spectrometry (LC-MS/MS). The species isolated were G. australes, which
produced MTX-1 (ranging from 3 to 36 pg/cell), and G. polynesiensis, which
produced neither MTX-1 nor, unusually, any known CTXs. Isolates of both species
produced putative MTX-3. The risk of fish, particularly herbivorous fish, causing
CFP in the Zealandia and Kermadec Islands region is real, although in mainland
New Zealand the risk is currently low. Both Gambierdiscus and Fukuyoa have been
recorded in the sub-tropical northern region of New Zealand, and so the risk may
increase with warming seas and shift in the distribution of Gambierdiscus
species.
PMID- 28696401
TI - Knowledge of and Attitudes to Influenza Vaccination among Community Pharmacists
in Catalonia (Spain). 2013-2014 Season: A Cross Sectional Study.
AB - Annual recommendations on influenza seasonal vaccination include community
pharmacists, who have low vaccination coverage. The aim of this study was to
investigate the relationship between influenza vaccination in community
pharmacists and their knowledge of and attitudes to vaccination. An online cross
sectional survey of community pharmacists in Catalonia, Spain, was conducted
between September and November 2014. Sociodemographic, professional and clinical
variables, the history of influenza vaccination and knowledge of and attitudes to
influenza and seasonal influenza vaccination were collected. The survey response
rate was 7.33% (506 out of 6906); responses from 463 community pharmacists were
included in the final analyses. Analyses were performed using multivariable
logistic regression models and stepwise backward selection method for variable
selection. The influenza vaccination coverage in season 2013-2014 was 25.1%.
There was an association between vaccination and correct knowledge of the virus
responsible for epidemics (adjusted Odds Ratio (aOR) = 1.74; 95% CI 1.03-2.95),
recommending vaccination in the postpartum (aOR = 3.63; 95% CI 2.01-6.55) and
concern about infecting their clients (aOR = 5.27; 95% CI 1.88-14.76). In
conclusion, community pharmacists have a very low influenza vaccination coverage,
are not very willing to recommend vaccination to all their customers but they are
concerned about infecting their clients.
PMID- 28696402
TI - Variability of Emaravirus Species Associated with Sterility Mosaic Disease of
Pigeonpea in India Provides Evidence of Segment Reassortment.
AB - Sterility mosaic disease (SMD) of pigeonpea is a serious constraint for
cultivation of pigeonpea in India and other South Asian countries. SMD of
pigeonpea is associated with two distinct emaraviruses, Pigeonpea sterility
mosaic virus 1 (PPSMV-1) and Pigeonpea sterility mosaic virus 2 (PPSMV-2), with
genomes consisting of five and six negative-sense RNA segments, respectively. The
recently published genome sequences of both PPSMV-1 and PPSMV-2 are from a single
location, Patancheru from the state of Telangana in India. However, here we
present the first report of sequence variability among 23 isolates of PPSMV-1 and
PPSMV-2, collected from ten locations representing six states of India. Both
PPSMV-1 and PPSMV-2 are shown to be present across India and to exhibit
considerable sequence variability. Variability of RNA3 sequences was higher than
the RNA4 sequences for both PPSMV-1 and PPSMV-2. Additionally, the sixth RNA
segment (RNA6), previously reported to be associated with only PPSMV-2, is also
associated with isolates of PPSMV-1. Multiplex reverse transcription PCR (RT-PCR)
analyses show that PPSMV-1 and PPSMV-2 frequently occur as mixed infections.
Further sequence analyses indicated the presence of reassortment of RNA4 between
isolates of PPSMV-1 and PPSMV-2.
PMID- 28696403
TI - Preschool and School Meal Policies: An Overview of What We Know about Regulation,
Implementation, and Impact on Diet in the UK, Sweden, and Australia.
AB - School meals make significant contributions to healthy dietary behaviour, at a
time when eating habits and food preferences are being formed. We provide an
overview of the approaches to the provision, regulation, and improvement of
preschool and primary school meals in the UK, Sweden, and Australia, three
countries which vary in their degree of centralisation and regulation of school
meals. Sweden has a centralised approach; all children receive free meals, and a
pedagogical approach to meals is encouraged. Legislation demands that meals are
nutritious. The UK system is varied and decentralised. Meals in most primary
schools are regulated by food-based standards, but preschool-specific meal
standards only exist in Scotland. The UK uses food groups (starchy foods, fruit
and vegetables, proteins and dairy) in a healthy plate approach. Australian
States and Territories all employ guidelines for school canteen food,
predominantly using a "traffic light" approach outlining recommended and
discouraged foods; however, most children bring food from home and are not
covered by this guidance. The preschool standards state that food provided should
be nutritious. We find that action is often lacking in the preschool years, and
suggest that consistent policies, strong incentives for compliance, systematic
monitoring, and an acknowledgement of the broader school eating environment
(including home provided food) would be beneficial.
PMID- 28696404
TI - Effect of Wind Farm Noise on Local Residents' Decision to Adopt Mitigation
Measures.
AB - Wind turbines' noise is frequently pointed out as the reason for local
communities' objection to the installation of wind farms. The literature suggests
that local residents feel annoyed by such noise and that, in many instances, this
is significant enough to make them adopt noise-abatement interventions on their
homes. Aiming at characterizing the relationship between wind turbine noise,
annoyance, and mitigating actions, we propose a novel conceptual framework. The
proposed framework posits that actual sound pressure levels of wind turbines
determine individual homes' noise-abatement decisions; in addition, the framework
analyzes the role that self-reported annoyance, and perception of noise levels,
plays on the relationship between actual noise pressure levels and those
decisions. The application of this framework to a particular case study shows
that noise perception and annoyance constitutes a link between the two.
Importantly, however, noise also directly affects people's decision to adopt
mitigating measures, independently of the reported annoyance.
PMID- 28696405
TI - Assessing Women's Negative Sanitation Experiences and Concerns: The Development
of a Novel Sanitation Insecurity Measure.
AB - Lack of access to acceptable sanitation facilities can expose individuals,
particularly women, to physical, social, and mental health risks. While some of
the challenges have been documented, standard metrics are needed to determine the
extent to which women have urination- and defecation-related concerns and
negative experiences. Such metrics also are needed to assess the effectiveness of
interventions to mitigate them. We developed a sanitation insecurity measure to
capture the range and frequency of women's sanitation-related concerns and
negative experiences. Research was conducted in rural Odisha, India with women
across various life course stages to reflect a range of perspectives. This paper
documents the mixed data collection methods and the exploratory and confirmatory
factor analyses we employed to arrive at a final measure. The final sanitation
insecurity measure includes 50 items across seven factors that reflect the
physical environment, the social environment, and individual-level constraints.
Most factor scores were significantly higher for unmarried women and for women
who lacked access to functional latrines, indicating social and environmental
influence on experiences. This measure will enable researchers to evaluate how
sanitation insecurity affects health and to determine if and how sanitation
interventions ameliorate women's concerns and negative experiences associated
with sanitation.
PMID- 28696406
TI - PCR-DGGE Analysis: Unravelling Complex Mixtures of Badnavirus Sequences Present
in Yam Germplasm.
AB - Badnaviruses (family Caulimoviridae, genus Badnavirus) have emerged as serious
pathogens especially affecting the cultivation of tropical crops. Badnavirus
sequences can be integrated in host genomes, complicating the detection of
episomal infections and the assessment of viral genetic diversity in samples
containing a complex mixture of sequences. Yam (Dioscorea spp.) plants are hosts
to a diverse range of badnavirus species, and recent findings have suggested that
mixed infections occur frequently in West African yam germplasm. Historically,
the determination of the diversity of badnaviruses present in yam breeding lines
has been achieved by cloning and sequencing of polymerase chain reaction (PCR)
products. In this study, the molecular diversity of partial reverse transcriptase
(RT)-ribonuclease H (RNaseH) sequences from yam badnaviruses was analysed using
PCR-dependent denaturing gradient gel electrophoresis (PCR-DGGE). This resulted
in the identification of complex 'fingerprints' composed of multiple sequences of
Dioscorea bacilliform viruses (DBVs). Many of these sequences show high
nucleotide identities to endogenous DBV (eDBV) sequences deposited in GenBank,
and fall into six monophyletic species groups. Our findings highlight PCR-DGGE as
a powerful tool in badnavirus diversity studies enabling a rapid indication of
sequence diversity as well as potential candidate integrated sequences revealed
by their conserved nature across germplasm.
PMID- 28696407
TI - Country and Gender-Specific Achievement of Healthy Nutrition and Physical
Activity Guidelines: Latent Class Analysis of 6266 University Students in Egypt,
Libya, and Palestine.
AB - Research on healthy behaviour such as physical activity and healthy nutrition and
their combination is lacking among university students in Arab countries. The
current survey assessed healthy nutrition, and moderate/vigorous physical
activity (PA) of 6266 students in Egypt, Libya, and Palestine. We computed a
nutrition guideline achievement index using WHO recommendation, as well as the
achievement of PA recommendations using guidelines for adults of the American
Heart Association guidelines. Latent class regression analysis identified
homogenous groups of male and female students, based on their achievements of
both guidelines. We examined associations between group membership and
achievement of guidelines. A three-class solution model best fitted the data,
generating three student Groups: "Healthy Eaters" (7.7% of females, 10.8% of
males), "Physically Active" (21.7% of females, 25.8% of males), and "Low Healthy
Behaviour" (70.6% of females, 63.4% of males). We did not observe a latent class
that exhibited combined healthy behaviours (physically active and healthy
eaters), and there were no major differences between countries. We observed a
very low rate of healthy nutrition (~10% of students achieved greater than four
of the eight nutrition guidelines), with little gender differences across the
countries. About 18-47% of students achieved the PA guidelines, depending on
country and gender, more often among males. Few females achieved the PA
guidelines, particularly in Libya and Palestine. Culturally adapted multi
behavioural interventions need to encourage healthy lifestyles, nutrition and PA
behaviours. National policies need to promote active living while addressing
cultural, geographic, and other barriers to young adults' engagement in PA.
PMID- 28696408
TI - A multi-protease, multi-dissociation, bottom-up-to-top-down proteomic view of the
Loxosceles intermedia venom.
AB - Venoms are a rich source for the discovery of molecules with biotechnological
applications, but their analysis is challenging even for state-of-the-art
proteomics. Here we report on a large-scale proteomic assessment of the venom of
Loxosceles intermedia, the so-called brown spider. Venom was extracted from 200
spiders and fractioned into two aliquots relative to a 10 kDa cutoff mass. Each
of these was further fractioned and digested with trypsin (4 h), trypsin (18 h),
pepsin (18 h), and chymotrypsin (18 h), then analyzed by MudPIT on an LTQ
Orbitrap XL ETD mass spectrometer fragmenting precursors by CID, HCD, and ETD.
Aliquots of undigested samples were also analyzed. Our experimental design
allowed us to apply spectral networks, thus enabling us to obtain meta-contig
assemblies, and consequently de novo sequencing of practically complete proteins,
culminating in a deep proteome assessment of the venom. Data are available via
ProteomeXchange, with identifier PXD005523.
PMID- 28696410
TI - A neural link between generosity and happiness.
AB - Generous behaviour is known to increase happiness, which could thereby motivate
generosity. In this study, we use functional magnetic resonance imaging and a
public pledge for future generosity to investigate the brain mechanisms that link
generous behaviour with increases in happiness. Participants promised to spend
money over the next 4 weeks either on others (experimental group) or on
themselves (control group). Here, we report that, compared to controls,
participants in the experimental group make more generous choices in an
independent decision-making task and show stronger increases in self-reported
happiness. Generous decisions engage the temporo-parietal junction (TPJ) in the
experimental more than in the control group and differentially modulate the
connectivity between TPJ and ventral striatum. Importantly, striatal activity
during generous decisions is directly related to changes in happiness. These
results demonstrate that top-down control of striatal activity plays a
fundamental role in linking commitment-induced generosity with happiness.
PMID- 28696409
TI - A global multiproxy database for temperature reconstructions of the Common Era.
AB - Reproducible climate reconstructions of the Common Era (1 CE to present) are key
to placing industrial-era warming into the context of natural climatic
variability. Here we present a community-sourced database of temperature
sensitive proxy records from the PAGES2k initiative. The database gathers 692
records from 648 locations, including all continental regions and major ocean
basins. The records are from trees, ice, sediment, corals, speleothems,
documentary evidence, and other archives. They range in length from 50 to 2000
years, with a median of 547 years, while temporal resolution ranges from biweekly
to centennial. Nearly half of the proxy time series are significantly correlated
with HadCRUT4.2 surface temperature over the period 1850-2014. Global temperature
composites show a remarkable degree of coherence between high- and low-resolution
archives, with broadly similar patterns across archive types, terrestrial versus
marine locations, and screening criteria. The database is suited to
investigations of global and regional temperature variability over the Common
Era, and is shared in the Linked Paleo Data (LiPD) format, including
serializations in Matlab, R and Python.
PMID- 28696411
TI - Combined study of genetic and epigenetic biomarker risperidone treatment efficacy
in Chinese Han schizophrenia patients.
AB - Nowadays, risperidone is an atypical antipsychotic drug that has been
increasingly used for treatment and maintenance therapy in schizophrenia.
However, partially affected by genetic or environmental factors, there is
significant difference in treatment outcomes among patients. In this study, we
aimed to interpret the difference between good and poor responders treated with
risperidone in both genetic and epigenetic levels in 288 mainland Chinese
patients. We recruited a Henan cohort including 98 patients as initial discovery
group and then confirmed our results in Shanghai cohort. In genetic studies, we
found 10 candidate single-nucleotide polymorphisms (SNPs) and 2 rare variants in
Henan cohort by next-generation sequencing of 100 risperidone-response-related
genes. After replication in Shanghai cohort by massarray platform, ultimately,
rs6706232 and rs4818 were significantly associated with risperidone response in
the two cohort meta-analysis (P=0.024 and 0.04, respectively). Besides, we also
selected another reported 17 candidate SNPs associated with risperidone drug
response to replicate in our mainland Chinese samples, while, we found no
significant SNPs after Bonferroni correction. In epigenetic studies, we
investigated the methylation status in promoters or gene-coding region of
risperidone drug response-related genes including CYP3A4, CYP2D6, ABCB1, HTR2A,
DRD2. Totally we found seven significant CpG sites in the meta-analysis with
Bonferroni-corrected PCYP3A4_CpG_-36=0.0014, PCYP3A4_CpG_-258=0.0013,
PCYP3A4_CpG_-296=0.0014, PCYP3A4_CpG_-367:-372:-374=0.028, PCYP2D6_CpG_193=0.012,
PCYP2D6_CpG_242:244:250=0.00076 and PCYP2D6_CpG_284=0.034, respectively. As
genetic and epigenetic factors may interactively affect drug response, we finally
carried out a multivariant interaction analysis with multifactor dimensionality
reduction and discovered a significant four-locus model (CYP3A4_CpG_-82:-86
+rs6280+rs1800497+rs6265, P=0.038) affecting drug response. These findings could
partially explain different risperidone response outcome in Chinese population in
a systematic level.
PMID- 28696412
TI - Whole-genome DNA methylation status associated with clinical PTSD measures of
OIF/OEF veterans.
AB - Emerging knowledge suggests that post-traumatic stress disorder (PTSD)
pathophysiology is linked to the patients' epigenetic changes, but comprehensive
studies examining genome-wide methylation have not been performed. In this study,
we examined genome-wide DNA methylation in peripheral whole blood in combat
veterans with and without PTSD to ascertain differentially methylated probes.
Discovery was initially made in a training sample comprising 48 male Operation
Enduring Freedom (OEF)/Operation Iraqi Freedom (OIF) veterans with PTSD and 51
age/ethnicity/gender-matched combat-exposed PTSD-negative controls. Agilent whole
genome array detected ~5600 differentially methylated CpG islands (CpGI)
annotated to ~2800 differently methylated genes (DMGs). The majority (84.5%) of
these CpGIs were hypermethylated in the PTSD cases. Functional analysis was
performed using the DMGs encoding the promoter-bound CpGIs to identify networks
related to PTSD. The identified networks were further validated by an independent
test set comprising 31 PTSD+/29 PTSD- veterans. Targeted bisulfite sequencing was
also used to confirm the methylation status of 20 DMGs shown to be highly
perturbed in the training set. To improve the statistical power and mitigate the
assay bias and batch effects, a union set combining both training and test set
was assayed using a different platform from Illumina. The pathways curated from
this analysis confirmed 65% of the pool of pathways mined from training and test
sets. The results highlight the importance of assay methodology and use of
independent samples for discovery and validation of differentially methylated
genes mined from whole blood. Nonetheless, the current study demonstrates that
several important epigenetically altered networks may distinguish combat-exposed
veterans with and without PTSD.
PMID- 28696413
TI - Genome-wide meta-analysis of copy number variations with alcohol dependence.
AB - Genetic association studies and meta-analyses of alcohol dependence (AD) have
reported AD-associated single nucleotide polymorphisms (SNPs). These SNPs
collectively account for a small portion of estimated heritability in AD. Recent
genome-wide copy number variation (CNV) studies have identified CNVs associated
with AD and substance dependence, suggesting that a portion of the missing
heritability is explained by CNV. We applied PennCNV and QuantiSNP CNV calling
algorithms to identify consensus CNVs in five AD cohorts of European and African
origins. After rigorous quality control, genome-wide meta-analyses of CNVs were
carried out in 3243 well-diagnosed AD cases and 2802 controls. We identified nine
CNV regions, including a deletion in chromosome 5q21.3 with a suggestive
association with AD (OR=2.15 (1.41-3.29) and P=3.8 * 10-4) and eight nominally
significant CNV regions. All regions were replicated with consistent effect sizes
across studies and populations. Pathway and gene-drug interaction enrichment
analyses based on the resulting genes indicated the mitogen-activated protein
kinase signaling pathway and the recombinant insulin and hyaluronidase drugs,
which were relevant to AD biology or treatment. To our knowledge, this is the
first genome-wide meta-analysis of CNVs with addiction. Further investigation of
the AD-associated CNV regions will provide better understanding of the AD genetic
mechanism.
PMID- 28696414
TI - Pharmacogenetics of oral antidiabetes drugs: evidence for diverse signals at the
IRS1 locus.
AB - To investigate the role of IRS1 locus on failure to oral antidiabetes drugs
(OADs) we genotyped single-nucleotide polymorphisms (SNPs), rs2943641, rs7578326
(tagging all SNPs genome-wide associated with type 2 diabetes (T2D) and related
traits at this locus) and rs1801278 (that is, the loss-of-function IRS1 G972R
amino acid substitution) in 2662 patients with T2D. Although no association with
OAD failure was observed for rs2943641 and rs7578326 SNPs (odds ratio (OR): 1.04,
95% confidence interval (CI): 0.93-1.16 and OR: 0.97, 95% CI: 0.87-1.09
respectively), a significant association was observed for rs1801278 (OR: 1.34,
95% CI: 1.08-1.66). When meta-analyzed with previous published data, an allelic
OR of 1.41 (1.15-1.72; P=0.001) was obtained, so that homozygous R972R
individuals have >80% higher risk of failing to OADs as compared with their G972G
counterparts. In all, though further studies are needed for confirming this
finding, our present data point to IRS1 rs1801278 as a potential biomarker for
pursuing the goal of stratified medicine in the field of antihyperglycemic
treatment in T2D.
PMID- 28696415
TI - Genome-wide association studies of placebo and duloxetine response in major
depressive disorder.
AB - We investigated variants associated with treatment response in depressed patients
treated with either the antidepressant duloxetine or placebo using a genome-wide
approach. Our sample (N=391) included individuals aged 18-75 years, diagnosed
with major depressive disorder and treated with either duloxetine or placebo for
up to 8 weeks. We conducted genome-wide associations for treatment response as
operationalized by percentage change in Montgomery-Asberg Depression Rating Scale
score from baseline, as well as mixed models analyses across five time points. In
the placebo-treated subsample (N=205), we observed a genome-wide association with
rs76767803 (beta=0.69, P=1.25 * 10-8) upstream of STAC1. STAC1 rs76767803 was
also associated with response using mixed model analysis (chi2=3.95; P=0.001). In
the duloxetine-treated subsample (N=186), we observed suggestive associations
with ZNF385D (rs4261893; beta=-0.46, P=1.55 * 10-5), NCAM1 (rs2303377; beta=0.45,
P=1.76 * 10-5) and MLL5 (rs117986340; beta=0.91, P=3.04 * 10-5). Our findings
suggest that a variant upstream of STAC1 is associated with placebo response,
which might have implications for treatment optimization, clinical trial design
and drug development.
PMID- 28696416
TI - Cytochrome P450 interactions are common and consequential in Massachusetts
hospital discharges.
AB - Despite the recognition that drug-drug interactions contribute substantially to
preventable health-care costs, the prevalence of such interactions related to the
cytochrome P450 system in clinical practice remains poorly characterized. This
study drew retrospective hospital discharge cohorts from a large health claims
data set and a large health system data set. For every hospital discharge,
frequency of co-occurrence of substrates and inducers or inhibitors at cytochrome
P450 2D6, 2C19, 3A4 and 1A2 were determined. A total of 124 520 individuals in
the state of Massachusetts (health claims cohort) and 77 026 individuals in two
large academic medical centers (electronic health record (EHR) cohort) were
examined. In the claims cohort, 35 157 (28.2%) exhibited at least one CYP450 drug
drug interaction at hospital discharge, whereas in the EHR cohort, 36 750 (47.7%)
had at least one interaction. The most commonly affected CYP450 systems were 2C19
and 2D6, with putative interactions observed in at least 10% of individuals at
discharge in each cohort. Odds of hospital readmission within 90 days among those
discharged with at least one interaction were 10-16% greater, with mean health
care cost $574/month greater over the subsequent year, after adjusting for age,
sex, insurance type, total number of medications prescribed, Charlson comorbidity
score and presence or absence of a psychiatric diagnosis. These two distinct
clinical data types show that CYP450 drug-drug interactions are prevalent and
associated with greater probability of early hospital readmission and greater
health-care cost, despite the widespread availability and application of drug
drug interaction checking software.
PMID- 28696417
TI - Harnessing low-density lipoprotein receptor protein 6 (LRP6) genetic variation
and Wnt signaling for innovative diagnostics in complex diseases.
AB - Wnt signaling regulates a broad variety of processes in both embryonic
development and various diseases. Recent studies indicated that some genetic
variants in Wnt signaling pathway may serve as predictors of diseases. Low
density lipoprotein receptor protein 6 (LRP6) is a Wnt co-receptor with essential
functions in the Wnt/beta-catenin pathway, and mutations in LRP6 gene are linked
to many complex human diseases, including metabolic syndrome, cancer, Alzheimer's
disease and osteoporosis. Therefore, we focus on the role of LRP6 genetic
polymorphisms and Wnt signaling in complex diseases, and the mechanisms from
mouse models and cell lines. It is also highly anticipated that LRP6 variants
will be applied clinically in the future. The brief review provided here could be
a useful resource for future research and may contribute to a more accurate
diagnosis in complex diseases.
PMID- 28696418
TI - Associations between functional polymorphisms and response to biological
treatment in Danish patients with psoriasis.
AB - Biological agents including anti-tumor necrosis factor (anti-TNF; adalimumab,
infliximab, etanercept) and anti-interleukin-12/13 (IL12/23; ustekinumab) are
essential for treatment of patients with severe psoriasis. However, a significant
proportion of the patients do not respond to a specific treatment.
Pharmacogenetics might be a way to predict treatment response. Using a candidate
gene approach, 62 mainly functional single-nucleotide polymorphisms (SNPs) in 44
different genes were evaluated in 478 Danish patients with psoriasis undergoing
376 series of anti-TNF treatment and 230 series of ustekinumab treatment.
Associations between genetic variants and treatment outcomes (drug survival and
Psoriasis Area Severity Index reduction) were assessed using logistic regression
analyses (crude and adjusted for gender, age, psoriatic arthritis and previous
treatment). After correction for multiple testing controlling the false discovery
rate, six SNPs (IL1B (rs1143623, rs1143627), LY96 (rs11465996), TLR2 (rs11938228,
rs4696480) and TLR9 (rs352139)) were associated with response to anti-TNF
treatment and 4 SNPs (IL1B (rs1143623, rs1143627), TIRAP (rs8177374) and TLR5
(rs5744174)) were associated with response to ustekinumab treatment (q<0.20). The
results suggest that genetic variants related to increased IL-1beta levels may be
unfavorable when treating psoriasis with either anti-TNF or ustekinumab, whereas
genetic variants related to high interferon-gamma levels may be favorable when
treating psoriasis with ustekinumab.
PMID- 28696419
TI - Associations between the C677T and A1298C polymorphisms of MTHFR and the toxicity
of methotrexate in childhood malignancies: a meta-analysis.
AB - As a common chemotherapy drug, methotrexate (MTX) has achieved remarkable
clinical success. However, high inter-individual variability and unpredictable
toxicity continue to challenge its use in clinical practices. Some studies
suggest this variation is associated with a methylenetetrahydrofolate reductase
(MTHFR) gene polymorphism, but results remain unclear. In this meta-analysis, we
include 14 studies that focus on MTHFR C677T and A1298C polymorphisms in
pediatric patients with malignancy. We found significant associations of the
MTHFR C677T polymorphism with hepatotoxicity (grade ?2; CC vs CT/TT: risk ratio
(RR): 0.82, 95% confidence interval (CI): 0.67-0.99; P=0.04), hematological
toxicity (grade 3-4; CC vs CT/TT: RR: 0.65, 95% CI: 0.44-0.97; P=0.03) in a
dominant genetic model and mucositis (grade ?3) in all models (CC vs CT/TT: RR:
0.18, 95% CI: 0.04-0.87; P=0.03; CC/CT vs TT: RR: 0.10, 95% CI: 0.03-0.32;
P?0.0001; CC vs TT: RR: 0.10, 95% CI: 0.02-0.50; P=0.005). No significant
association was found with the MTHFR A1298C polymorphism. For children with
malignancy, genotyping of the MTHFR C677T polymorphism is expected to be a useful
tool in reducing toxicity and improving outcome in personalized MTX therapy.
PMID- 28696420
TI - A cost-effectiveness analysis of maternal CYP2D6 genetic testing to guide
treatment for postpartum pain and avert infant adverse events.
AB - Mothers with a CYP2D6 ultrarapid metabolizer phenotype may expose their infants
to risk of adverse events when taking codeine while breastfeeding, by producing
more of the active metabolite, morphine. Pharmacogenetic testing may be a
valuable tool to identify such mothers, but testing can be costly. The objective
of the study was to determine the incremental costs of genotyping to avert
neonatal adverse events during maternal pharmacotherapy. A cost-effectiveness
analysis, using a decision model, was performed with a hypothetical cohort of
prenatal subjects. Parameter estimates, costs and ranges for sensitivity analyses
were ascertained from the literature and expert opinion. Sensitivity analyses
were conducted to assess the robustness of the results. Probabilistic sensitivity
analysis revealed an incremental cost-effectiveness (ICER) of $10 433 (Canadian
dollars) for genotyping compared to no genotyping per adverse event averted.
Results were sensitive to hospital admission costs. The ICER was lower when
evaluating only subjects having caesarean deliveries or those from ethnic
populations known to have a high prevalence of ultra-rapid metabolizers. Although
genotyping to guide pharmacotherapy was not cost saving, the cost to avert an
infant adverse event may represent good value for money in specific populations.
With a growing demand for personalized medicine, these findings are relevant for
decision makers, clinicians and patients.
PMID- 28696421
TI - Erratum: A new, long-term daily satellite-based rainfall dataset for operational
monitoring in Africa.
AB - This corrects the article DOI: 10.1038/sdata.2017.63.
PMID- 28696422
TI - Metagenomic binning of a marine sponge microbiome reveals unity in defense but
metabolic specialization.
AB - Marine sponges are ancient metazoans that are populated by distinct and highly
diverse microbial communities. In order to obtain deeper insights into the
functional gene repertoire of the Mediterranean sponge Aplysina aerophoba, we
combined Illumina short-read and PacBio long-read sequencing followed by un
targeted metagenomic binning. We identified a total of 37 high-quality bins
representing 11 bacterial phyla and two candidate phyla. Statistical comparison
of symbiont genomes with selected reference genomes revealed a significant
enrichment of genes related to bacterial defense (restriction-modification
systems, toxin-antitoxin systems) as well as genes involved in host colonization
and extracellular matrix utilization in sponge symbionts. A within-symbionts
genome comparison revealed a nutritional specialization of at least two symbiont
guilds, where one appears to metabolize carnitine and the other sulfated
polysaccharides, both of which are abundant molecules in the sponge extracellular
matrix. A third guild of symbionts may be viewed as nutritional generalists that
perform largely the same metabolic pathways but lack such extraordinary numbers
of the relevant genes. This study characterizes the genomic repertoire of sponge
symbionts at an unprecedented resolution and it provides greater insights into
the molecular mechanisms underlying microbial-sponge symbiosis.
PMID- 28696423
TI - Optimised chronic infection models demonstrate that siderophore 'cheating' in
Pseudomonas aeruginosa is context specific.
AB - The potential for siderophore mutants of Pseudomonas aeruginosa to attenuate
virulence during infection, and the possibility of exploiting this for clinical
ends, have attracted much discussion. This has largely been based on the results
of in vitro experiments conducted in iron-limited growth medium, in which
siderophore mutants act as social 'cheats:' increasing in frequency at the
expense of the wild type to result in low-productivity, low-virulence populations
dominated by mutants. We show that insights from in vitro experiments cannot
necessarily be transferred to infection contexts. First, most published
experiments use an undefined siderophore mutant. Whole-genome sequencing of this
strain revealed a range of mutations affecting phenotypes other than siderophore
production. Second, iron-limited medium provides a very different environment
from that encountered in chronic infections. We conducted cheating assays using
defined siderophore deletion mutants, in conditions designed to model infected
fluids and tissue in cystic fibrosis lung infection and non-healing wounds.
Depending on the environment, siderophore loss led to cheating, simple fitness
defects, or no fitness effect at all. Our results show that it is crucial to
develop defined in vitro models in order to predict whether siderophores are
social, cheatable and suitable for clinical exploitation in specific infection
contexts.
PMID- 28696424
TI - Phenotypic and genotypic richness of denitrifiers revealed by a novel isolation
strategy.
AB - Present-day knowledge on the regulatory biology of denitrification is based on
studies of selected model organisms. These show large variations in their
potential contribution to NO2-, NO, and N2O accumulation, attributed to lack of
genes coding for denitrification reductases, but also to variations in their
transcriptional regulation, as well as to post-transcriptional phenomena. To
validate the relevance of these observations, there is a need to study a wider
range of denitrifiers. We designed an isolation protocol that identifies all
possible combinations of truncated denitrification chains (NO3-/NO2-/NO/N2O/N2).
Of 176 isolates from two soils (pH 3.7 and 7.4), 30 were denitrifiers sensu
stricto, reducing NO2- to gas, and five capable of N2O reduction only.
Altogether, 70 isolates performed at least one reduction step, including two DNRA
isolates. Gas kinetics and electron flow calculations revealed that several
features with potential impact on N2O production, reported from model organisms,
also exist in these novel isolates, including denitrification bet-hedging and
control of NO2-/NO/N2O accumulation. Whole genome sequencing confirmed most
truncations but also showed that phenotypes cannot be predicted solely from
genetic potential. Interestingly, and opposed to the commonly observed inability
to reduce N2O under acidic conditions, one isolate identified as Rhodanobacter
reduced N2O only at low pH.
PMID- 28696425
TI - Microbial survival strategies in ancient permafrost: insights from metagenomics.
AB - In permafrost (perennially frozen ground) microbes survive oligotrophic
conditions, sub-zero temperatures, low water availability and high salinity over
millennia. Viable life exists in permafrost tens of thousands of years old but we
know little about the metabolic and physiological adaptations to the challenges
presented by life in frozen ground over geologic time. In this study we asked
whether increasing age and the associated stressors drive adaptive changes in
community composition and function. We conducted deep metagenomic and 16 S rRNA
gene sequencing across a Pleistocene permafrost chronosequence from 19 000 to 33
000 years before present (kyr). We found that age markedly affected community
composition and reduced diversity. Reconstruction of paleovegetation from
metagenomic sequence suggests vegetation differences in the paleo record are not
responsible for shifts in community composition and function. Rather, we observed
shifts consistent with long-term survival strategies in extreme cryogenic
environments. These include increased reliance on scavenging detrital biomass,
horizontal gene transfer, chemotaxis, dormancy, environmental sensing and stress
response. Our results identify traits that may enable survival in ancient
cryoenvironments with no influx of energy or new materials.
PMID- 28696427
TI - Giving research a sporting chance.
PMID- 28696426
TI - An imaging dataset of cervical cells using scanning near-field optical microscopy
coupled to an infrared free electron laser.
AB - Using a scanning near-field optical microscope coupled to an infrared free
electron laser (SNOM-IR-FEL) in low-resolution transmission mode, we collected
chemical data from whole cervical cells obtained from 5 pre-menopausal, non
pregnant women of reproductive age, and cytologically classified as normal or
with different grades of cervical cell dyskaryosis. Imaging data are complemented
by demography. All samples were collected before any treatment. Spectra were also
collected using attenuated total reflection, Fourier-transform (ATR-FTIR)
spectroscopy, to investigate the differences between the two techniques. Results
of this pilot study suggests SNOM-IR-FEL may be able to distinguish cervical
abnormalities based upon changes in the chemical profiles for each grade of
dyskaryosis at designated wavelengths associated with DNA, Amide I/II, and
lipids. The novel data sets are the first collected using SNOM-IR-FEL in
transmission mode at the ALICE facility (UK), and obtained using whole cells as
opposed to tissue sections, thus providing an 'intact' chemical profile. These
data sets are suited to complementing future work on image analysis, and/or
applying the newly developed algorithm to other datasets collected using the SNOM
IR-FEL approach.
PMID- 28696428
TI - Growing the lost crops of eastern North America's original agricultural system.
AB - Thousands of years before the maize-based agriculture practiced by many Native
American societies in eastern North America at the time of contact with
Europeans, there existed a unique crop system only known through archaeological
evidence. There are no written or oral records of how these lost crops were
cultivated, but several domesticated subspecies have been identified in the
archaeological record. Growth experiments and observations of living progenitors
of these crops can provide insights into the ancient agricultural system of
eastern North America, the role of developmental plasticity in the process of
domestication, and the creation and maintenance of diverse landraces under
cultivation. In addition, experimental gardens are potent tools for public
education, and can also be used to conserve remaining populations of lost crop
progenitors and explore the possibility of re-domesticating these species.
PMID- 28696429
TI - GluD1, linked to schizophrenia, controls the burst firing of dopamine neurons.
AB - Human mutations of the GRID1 gene encoding the orphan delta1 glutamate receptor
channel (GluD1) are associated with schizophrenia but the explicit role of GluD1
in brain circuits is unknown. Based on the known function of its paralog GluD2 in
cerebellum, we searched for a role of GluD1 in slow glutamatergic transmission
mediated by metabotropic receptor mGlu1 in midbrain dopamine neurons, whose
dysfunction is a hallmark of schizophrenia. We found that an mGlu1 agonist
elicits a slow depolarizing current in HEK cells co-expressing mGlu1 and GluD1,
but not in cells expressing mGlu1 or GluD1 alone. This current is abolished by
additional co-expression of a dominant-negative GluD1 dead pore mutant. We then
characterized mGlu1-dependent currents in dopamine neurons from midbrain slices.
Both the agonist-evoked and the slow postsynaptic currents are abolished by
expression of the dominant-negative GluD1 mutant, pointing to the involvement of
native GluD1 channels in these currents. Likewise, both mGlu1-dependent currents
are suppressed in GRID1 knockout mice, which reportedly display endophenotypes
relevant for schizophrenia. It is known that mGlu1 activation triggers the
transition from tonic to burst firing of dopamine neurons, which signals salient
stimuli and encodes reward prediction. In vivo recordings of dopamine neurons
showed that their spontaneous burst firing is abolished in GRID1 knockout mice or
upon targeted expression of the dominant-negative GluD1 mutant in wild-type mice.
Our results de-orphanize GluD1, unravel its key role in slow glutamatergic
transmission and provide insights into how GRID1 gene alterations can lead to
dopaminergic dysfunctions in schizophrenia.
PMID- 28696431
TI - Synaptic activity protects against AD and FTD-like pathology via autophagic
lysosomal degradation.
AB - Changes in synaptic excitability and reduced brain metabolism are among the
earliest detectable alterations associated with the development of Alzheimer's
disease (AD). Stimulation of synaptic activity has been shown to be protective in
models of AD beta-amyloidosis. Remarkably, deep brain stimulation (DBS) provides
beneficial effects in AD patients, and represents an important therapeutic
approach against AD and other forms of dementia. While several studies have
explored the effect of synaptic activation on beta-amyloid, little is known about
Tau protein. In this study, we investigated the effect of synaptic stimulation on
Tau pathology and synapses in in vivo and in vitro models of AD and
frontotemporal dementia (FTD). We found that chronic DBS or chemically induced
synaptic stimulation reduced accumulation of pathological forms of Tau and
protected synapses, while chronic inhibition of synaptic activity worsened Tau
pathology and caused detrimental effects on pre- and post-synaptic markers,
suggesting that synapses are affected. Interestingly, degradation via the
proteasomal system was not involved in the reduction of pathological Tau during
stimulation. In contrast, chronic synaptic activation promoted clearance of Tau
oligomers by autophagosomes and lysosomes. Chronic inhibition of synaptic
activity resulted in opposite outcomes, with build-up of Tau oligomers in
enlarged auto-lysosomes. Our data indicate that synaptic activity counteracts the
negative effects of Tau in AD and FTD by acting on autophagy, providing a
rationale for therapeutic use of DBS and synaptic stimulation in tauopathies.
PMID- 28696432
TI - Cross-disorder risk gene CACNA1C differentially modulates susceptibility to
psychiatric disorders during development and adulthood.
AB - Single-nucleotide polymorphisms (SNPs) in CACNA1C, the alpha1C subunit of the
voltage-gated L-type calcium channel Cav1.2, rank among the most consistent and
replicable genetics findings in psychiatry and have been associated with
schizophrenia, bipolar disorder and major depression. However, genetic variants
of complex diseases often only confer a marginal increase in disease risk, which
is additionally influenced by the environment. Here we show that embryonic
deletion of Cacna1c in forebrain glutamatergic neurons promotes the manifestation
of endophenotypes related to psychiatric disorders including cognitive decline,
impaired synaptic plasticity, reduced sociability, hyperactivity and increased
anxiety. Additional analyses revealed that depletion of Cacna1c during embryonic
development also increases the susceptibility to chronic stress, which suggest
that Cav1.2 interacts with the environment to shape disease vulnerability.
Remarkably, this was not observed when Cacna1c was deleted in glutamatergic
neurons during adulthood, where the later deletion even improved cognitive
flexibility, strengthened synaptic plasticity and induced stress resilience. In a
parallel gene * environment design in humans, we additionally demonstrate that
SNPs in CACNA1C significantly interact with adverse life events to alter the risk
to develop symptoms of psychiatric disorders. Overall, our results further
validate Cacna1c as a cross-disorder risk gene in mice and humans, and
additionally suggest a differential role for Cav1.2 during development and
adulthood in shaping cognition, sociability, emotional behavior and stress
susceptibility. This may prompt the consideration for pharmacological
manipulation of Cav1.2 in neuropsychiatric disorders with developmental and/or
stress-related origins.
PMID- 28696433
TI - Elevated plasma ferritin in elderly individuals with high neocortical amyloid
beta load.
AB - Ferritin, an iron storage and regulation protein, has been associated with
Alzheimer's disease (AD); however, it has not been investigated in preclinical
AD, detected by neocortical amyloid-beta load (NAL), before cognitive impairment.
Cross-sectional analyses were carried out for plasma and serum ferritin in
participants in the Kerr Anglican Retirement Village Initiative in Aging Health
cohort. Subjects were aged 65-90 years and were categorized into high and low NAL
groups via positron emission tomography using a standard uptake value ratio
cutoff=1.35. Ferritin was significantly elevated in participants with high NAL
compared with those with low NAL, adjusted for covariates age, sex,
apolipoprotein E E4 carriage and levels of C-reactive protein (an inflammation
marker). Ferritin was also observed to correlate positively with NAL. A receiver
operating characteristic curve based on a logistic regression of the same
covariates, the base model, distinguished high from low NAL (area under the curve
(AUC)=0.766), but was outperformed when plasma ferritin was added to the base
model (AUC=0.810), such that at 75% sensitivity, the specificity increased from
62 to 71% on adding ferritin to the base model, indicating that ferritin is a
statistically significant additional predictor of NAL over and above the base
model. However, ferritin's contribution alone is relatively minor compared with
the base model. The current findings suggest that impaired iron mobilization is
an early event in AD pathogenesis. Observations from the present study highlight
ferritin's potential to contribute to a blood biomarker panel for preclinical AD.
PMID- 28696430
TI - Neuropathology of suicide: recent findings and future directions.
AB - Suicide is a major public health concern and a leading cause of death in most
societies. Suicidal behaviour is complex and heterogeneous, likely resulting from
several causes. It associates with multiple factors, including psychopathology,
personality traits, early-life adversity and stressful life events, among others.
Over the past decades, studies in fields ranging from neuroanatomy, genetics and
molecular psychiatry have led to a model whereby behavioural dysregulation,
including suicidal behaviour (SB), develops as a function of biological
adaptations in key brain systems. More recently, the unravelling of the unique
epigenetic processes that occur in the brain has opened promising avenues in
suicide research. The present review explores the various facets of the current
knowledge on suicidality and discusses how the rapidly evolving field of
neurobehavioural epigenetics may fuel our ability to understand, and potentially
prevent, SB.
PMID- 28696434
TI - When should governments increase the supply of psychiatric beds?
AB - Low numbers of hospital-based psychiatric beds create problems for people with
severe mental illness (SMI), when they face extended emergency department (ED)
waits, higher thresholds for admission to an acute bed, and short revolving-door
stays with high rates of rehospitalisation. Limited access to inpatient treatment
has been associated with higher suicide risk, premature mortality, homelessness,
violent crime and incarceration. Ultimately, people with SMI can be
transinstitutionalised to the criminal justice system. In the USA, for example,
prisons have replaced mental hospitals as the largest institutions housing people
with SMI. There is no international consensus on the safe minimum numbers of
acute, forensic and rehabilitation beds needed to reduce these risks. As a
consequence, Organisation for Economic Cooperation and Development (OECD)
countries have wide variations in the mix of hospital beds with an average of 71
beds per 100 000 population. Policymakers face difficult choices with few studies
to guide decisions on supplying beds. The UK Royal College of Psychiatrists
offered a policy framework, which was adapted for Australia. The government of
the State of South Australia increased the supplies of crisis, acute and forensic
beds to meet a mandatory target to safely reduce mental health boarding in the
EDs.
PMID- 28696435
TI - A direct test of the diathesis-stress model for depression.
AB - The diathesis-stress theory for depression states that the effects of stress on
the depression risk are dependent on the diathesis or vulnerability, implying
multiplicative interactive effects on the liability scale. We used polygenic risk
scores for major depressive disorder (MDD) calculated from the results of the
most recent analysis from the Psychiatric Genomics Consortium as a direct measure
of the vulnerability for depression in a sample of 5221 individuals from 3083
families. In the same we also had measures of stressful life events and social
support and a depression symptom score, as well as DSM-IV MDD diagnoses for most
individuals. In order to estimate the variance in depression explained by the
genetic vulnerability, the stressors and their interactions, we fitted linear
mixed models controlling for relatedness for the whole sample as well as
stratified by sex. We show a significant interaction of the polygenic risk scores
with personal life events (0.12% of variance explained, P-value=0.0076)
contributing positively to the risk of depression. Additionally, our results
suggest possible differences in the aetiology of depression between women and
men. In conclusion, our findings point to an extra risk for individuals with
combined vulnerability and high number of reported personal life events beyond
what would be expected from the additive contributions of these factors to the
liability for depression, supporting the multiplicative diathesis-stress model
for this disease.
PMID- 28696437
TI - Autocatalytic dioxygen activation to produce an iron(v)-oxo complex without any
reductants.
AB - An iron(v)-oxo complex with a tetraamido macrocyclic ligand, [(TAML)FeV(O)]-, was
produced by reacting [(TAML)FeIII]- with dioxygen without any electron source in
acetone at 298 K. The autocatalytic mechanism of dioxygen activation for the
formation of an iron(v)-oxo complex has been clarified based on the autocatalysis
by radical chain initiators.
PMID- 28696436
TI - Reduced TRPC6 mRNA levels in the blood cells of patients with Alzheimer's disease
and mild cognitive impairment.
AB - Transient receptor potential canonical 6 (TRPC6) inhibits beta-amyloid (Abeta)
production. Hyperforin, the TRPC6 agonist, reduces Abeta levels and improves
cognitive performance in Alzheimer's disease (AD) models. However, it's unknown
whether TRPC6 expression is changed in AD patients. In this case-control study,
we measured TRPC6 expression levels in the peripheral blood cells of four
independent AD sets from five hospitals and one mild cognitive impairment (MCI)
set from a local community (229 AD, 70 MCI, 40 Parkinson disease and 359 controls
from China, total n=698) using quantitative real-time PCR assay. We found a
specific reduction of TRPC6 mRNA levels in four AD sets and one MCI set. The
median TRPC6 mRNA levels were lower in the following: (1) combined AD patients
than in age-matched controls (0.78 vs 1.73, P<0.001); (2) mild-to-moderate AD
patients than in age-matched controls (0.81 vs 1.73, P<0.001); and (3) MCI
patients than in age-matched controls (0.76 vs 1.72, P<0.001). In the receiver
operating characteristic curve analysis, the area under curve was 0.85 for
combined AD, 0.84 for mild-to-moderate AD and 0.79 for MCI. In a subgroup of AD
patients with brain Abeta examination, TRPC6 was associated with standardized
uptake value ratio of Pittsburgh Compound B (Spearman's r=-0.49, P=0.04) and
cerebrospinal fluid Abeta42 (Spearman's r=0.43, P=0.04). The TRPC6 reduction in
AD patients was further confirmed in blood RNA samples from The Australian
Imaging, Biomarkers and Lifestyle Flagship Study of Aging, in post-mortem brain
tissues from The Netherlands Brain Bank and in induced pluripotent stem cells
derived neurons from Chinese donors. We conclude that TRPC6 mRNA levels in the
blood cells are specifically reduced in AD and MCI patients, and TRPC6 might be a
biomarker for the early diagnosis of AD.
PMID- 28696438
TI - Self-assembly of melem on Au(111) and Ag(111): the origin of two different
hydrogen bonding configurations.
AB - We studied the self-assembly of melem on the Au(111) and Ag(111) surfaces. By
scanning tunneling microscopy imaging, we observed two different STM appearances
of the melem molecule within the self-assembled nanostructure on Au(111), which
resulted from the different intermolecular bonding configurations. Moreover,
further DFT details including the intermolecular charge density difference and
bonding energy were also obtained to compare the different natures of the
intermolecular bonding configurations.
PMID- 28696439
TI - Nanocrystalline cellulose mediated seed-growth for ultra-robust colorimetric
detection of hydrogen sulfide.
AB - We describe an ultra-stable, ultra-robust, straightforward and low-cost approach
for the colorimetric detection of H2S with nanocrystalline cellulose (NCC) based
on the reaction of H2S with lead acetate. The presence of NCC not only mediates
the seed growth of a PbS/NCC complex, but also acts as a stabilizer protecting
PbS from precipitation. This stable system is so robust that it can be used to
quantitatively detect H2S even after two-year storage.
PMID- 28696440
TI - Schottky barrier and band edge engineering via the interfacial structure and
strain for the Pt/TiO2 heterostructure.
AB - Charge transfer across the Pt/TiO2 interface, which is mainly determined by the
interface Schottky barrier height (SBH), is an important process in the
(photo)catalytic and electronic applications of the Pt/TiO2 composite. Therefore,
systematic investigation of the factors that affect the interface SBH is
indispensable for understanding and optimizing its performance. In this work, a
systematic study of the effects of the interfacial structure and strain on the
SBH of the Pt/TiO2(001) interface has been carried out based on the first
principles calculations. The results of interface adhesion energy show that two
different interfacial structures for the Pt/TiO2(001) heterointerface may exist
experimentally, namely, O-Pt bonding and Ti-Pt bonding. Moreover, the interfacial
structures result in not only different values for the SBH, but also different
dependences of the SBH on strain. Detailed investigations show that these
versatile modulations of the SBH with the structure and strain are mainly
attributed to the strong dependence of the band edges of TiO2 and the interfacial
potential alignments on the strain and structure, suggesting that these results
are general and may be applicable to other metal/TiO2 heterostructures.
PMID- 28696441
TI - Directed assembly of functionalized nanoparticles with amphiphilic diblock
copolymers.
AB - The ability to design and fabricate highly ordered superstructures from nanoscale
particles remains a major scientific and technological challenge. Patchy
nanoparticles have recently emerged as a novel class of building units to
construct functional materials. Using simulations of coarse-grained molecular
dynamics, we propose a simple approach to achieve soft nanoparticles with a self
patchiness nature through self-assembly of tethered copolymers with a sequence of
inner solvophilic and outer solvophobic blocks. As building units, the patch-like
nanoparticles are directed to further assemble into a rich variety of highly
ordered superstructures via condensation-coalescence mechanisms. The growth
kinetics of the superstructures obeys the kinetic model of the step-growth
polymerization process. Our simulations also demonstrate that the intermediate
patch-like nanoparticles and the final assembled superstructures can be
rationally tuned by changing the number and the composition of the tethered
copolymer chains. This strategy of copolymer functionalization conceptually
enables the design and fabrication of highly ordered superstructures of
nanoparticle ensembles with new horizons for promising applications in soft
nanotechnology and biotechnology.
PMID- 28696442
TI - Reducing hole transporter use and increasing perovskite solar cell stability with
dual-role polystyrene microgel particles.
AB - Perovskite solar cells (PSCs) are a disruptive technology that continues to
attract considerable attention due to their remarkable and sustained power
conversion efficiency increase. Improving PSC stability and reducing expensive
hole transport material (HTM) usage are two aspects that are gaining increased
attention. In a new approach, we investigate the ability of insulating
polystyrene microgel particles (MGs) to increase PSC stability and replace the
majority of the HTM phase. MGs are sub-micrometre crosslinked polymer particles
that swell in a good solvent. The MGs were prepared using a scalable emulsion
polymerisation method. Mixed HTM/MG dispersions were subsequently spin-coated
onto PSCs and formed composite HTM-MG layers. The HTMs employed were poly(triaryl
amine) (PTAA), poly(3-hexylthiophene) (P3HT) and Spiro-MeOTAD (Spiro). The MGs
formed mechanically robust composite HTMs with PTAA and P3HT. In contrast, Spiro
MG composites contained micro-cracks due the inability of the relatively small
Spiro molecules to interdigitate. The efficiencies for the PSCs containing PTAA
MG and P3HT-MG decreased by only ~20% compared to control PSCs despite PTAA and
P3HT being the minority phases. They occupied only ~35 vol% of the composite
HTMs. An unexpected finding from the study was that the MGs dispersed well within
the PTAA matrix. This morphology aided strong quenching of the CH3NH3PbI3-xClx
fluorescence. In addition, the open circuit voltages for the PSCs prepared using
P3HT-MG increased by ~170 mV compared to control PSCs. To demonstrate their
versatility the MGs were also used to encapsulate P3HT-based PSCs. Solar cell
stability data for the latter as well as those for PSCs containing composite HTM
MG were both far superior compared to data measured for a control PSC. Since MGs
can reduce conjugated polymer use and increase stability they have good potential
as dual-role PSC additives.
PMID- 28696443
TI - A facile synthesis of novel near-infrared pyrrolopyrrole aza-BODIPY luminogens
with aggregation-enhanced emission characteristics.
AB - Here we report the facile synthesis of two triphenylethylene-modified
pyrrolopyrrole aza-BODIPY dyes with an aggregation-enhanced emission feature. NIR
emitting nanoparticles with remarkable photostability properties and applications
in bioimaging were generated due to their good dispersity in water and
biocompatibility.
PMID- 28696444
TI - Facile electrospinning formation of carbon-confined metal oxide cube-in-tube
nanostructures for stable lithium storage.
AB - A unique carbon-confined metal oxide cube-in-tube nanostructure is synthesized by
a facile precursor-modified electrospinning method with subsequent pyrolysis.
This nanostructure has a partly graphitized carbon layer with manganese oxide
nanoparticles embedded as the tube and amorphous CoSnO3 hollow cubes uniformly
distributed inside the tube. As a lithium-ion battery anode, this architecture
exhibits a high reversible discharge capacity and rate capability.
PMID- 28696445
TI - Binding modes and pathway of RHPS4 to human telomeric G-quadruplex and duplex DNA
probed by all-atom molecular dynamics simulations with explicit solvent.
AB - RHPS4, a potent binder to human telomeric DNA G-quadruplex, shows high efficacy
in tumor cell growth inhibition. However, it's preferential binding to DNA G
quadruplex over DNA duplex (about 10 fold) remains to be improved toward its
clinical application. A high resolution structure of the single-stranded
telomeric DNA G-quadruplexes, or B-DNA duplex, in complex with RHPS4 is not
available yet, and the binding nature of this ligand to these DNA forms remains
to be elusive. In this study, we carried out 40 MUs molecular dynamics binding
simulations with a free ligand to decipher the binding pathway of RHPS4 to a DNA
duplex and three G-quadruplex folders (parallel, antiparallel and hybrid) of the
human telomeric DNA sequence. The most stable binding mode identified for the
duplex, parallel, antiparallel and hybrid G-quadruplexes is an intercalation,
bottom stacking, top intercalation and bottom intercalation mode, respectively.
The intercalation mode with similar binding strength to both the duplex and the G
quadruplexes, explains the lack of binding selectivity of RHPS4 to the G
quadruplex form. Therefore, a ligand modification that destabilizes the duplex
intercalation mode but stabilizes the G-quadruplex intercalation mode will
improve the binding selectivity toward G-quadruplex. The intercalation mode of
RHPS4 to both the duplex and the antiparallel and the hybrid G-quadruplex follows
a base flipping-insertion mechanism rather than an open-insertion mechanism. The
groove binding, the side binding and the intercalation with flipping out of base
were observed to be intermediate states before the full intercalation state with
paired bases.
PMID- 28696446
TI - Inhibitors or toxins? Large library target-specific screening of fullerene-based
nanoparticles for drug design purpose.
AB - Fullerene-based nanoparticles have been the subject of vital interest due to
their unique properties and potential application in many areas, including
medicine. Here we explore their characteristics that could make them prospective
leads for known disease-related proteins. High-throughput virtual screening
supported by comprehensive multi-software protein-ligand docking simulation and
cheminformatics approaches has been applied in investigation of interactions of
1117 proteins with a 169 fullerene nanoparticles decorated with different small
molecules. Moreover, obtained docking results were confirmed by the series of
unrestricted all-atom molecular dynamics (MD) simulations. Hydrophobicity of
fullerene core along with hydrophilic interaction of side chains plays a key role
in binding with the studied proteins. We identified a series of nanoparticles
that can lead to development of robust drugs for target proteins and another
series that can behave as a highly toxic agent. The structure-activity
relationship analysis revealed two significant molecular properties responsible
for the binding score values. The application of carefully selected computational
techniques and described outcome of the study facilitate development of
functional fullerene nanoparticles for drug-like and drug delivery applications.
PMID- 28696448
TI - AuAg@CdS double-walled nanotubes: synthesis and nonlinear absorption properties.
AB - Novel AuAg@CdS double-walled nanotubes (DWNTs) were successfully fabricated
through a three-step solvothermal method, starting with silver nanowires as the
template. In the DWNTs, a uniform layer of a CdS shell is coated onto the AuAg
nanotubes, finally forming the one-dimensional nanocomposites. Nonlinear optical
analysis indicated that the plasmon-exciton interaction in the AuAg@CdS DWNTs
induced an obviously saturated absorption response under visible light
excitation, in contrast to individual AuAg nanotubes and CdS shells. Furthermore,
the effective nonlinear absorption coefficient of the AuAg@CdS DWNTs was 7 times
larger than that of the CdS shell, which was attributed to the local field
enhancement effect. Such a unique morphological configuration and optical
properties make AuAg@CdS DWNTs an ideal candidate for next generation nano
photonic devices employed as a mode-locking element, optical switch, and so on.
PMID- 28696450
TI - Tuning the coercivity and exchange bias by controlling the interface coupling in
bimagnetic core/shell nanoparticles.
AB - In order to explore an alternative strategy to design exchange-biased magnetic
nanostructures, bimagnetic core/shell nanoparticles have been fabricated by a
thermal decomposition method and systematically studied as a function of the
interface exchange coupling. The nanoparticles are constituted by a ~3 nm
antiferromagnetic (AFM) CoO core encapsulated in a ~4 nm-thick Co1-xZnxFe2O4 (x =
0-1) ferrimagnetic (FiM) shell. The system presents an enhancement of the
coercivity (HC) as compared to its FiM single-phase counterpart and exchange bias
fields (HEB). While HC decreases monotonically with the Zn concentration from
~21.5 kOe for x = 0, to ~7.1 kOe for x = 1, HEB exhibits a non-monotonous
behavior being maximum, HEB ~ 1.4 kOe, for intermediate concentrations. We found
that the relationship between the AFM anisotropy energy and the exchange coupling
energy can be tuned by replacing Co2+ with Zn2+ ions in the shell. As a
consequence, the magnetization reversal mechanism of the system is changed from
an AFM/FiM rigid-coupling regime to an exchange-biased regime, providing a new
approach to tune the magnetic properties and to design novel hybrid
nanostructures.
PMID- 28696451
TI - An unprecedented trinuclear FeII triazole-based complex exhibiting a concerted
and complete sharp spin transition above room temperature.
AB - We report a triazole-based trinuclear complex as the first example that displays
a complete one-step first-order [HS-HS-HS] <-> [LS-LS-LS] spin transition at 318
K. The strong ferro-elastic interactions, between the three metal centers, have
been identified as the source of the concerted spin transition in this trinuclear
complex.
PMID- 28696452
TI - Platinum nanoparticles in nanobiomedicine.
AB - Oxidative stress-dependent inflammatory diseases represent a major concern for
the population's health worldwide. Biocompatible nanomaterials with enzymatic
properties could play a crucial role in the treatment of such pathologies. In
this respect, platinum nanoparticles (PtNPs) are promising candidates, showing
remarkable catalytic activity, able to reduce the intracellular reactive oxygen
species (ROS) levels and impair the downstream pathways leading to inflammation.
This review reports a critical overview of the growing evidence revealing the
anti-inflammatory ability of PtNPs and their potential applications in
nanomedicine. It provides a detailed description of the wide variety of synthetic
methods recently developed, with particular attention to the aspects influencing
biocompatibility. Special attention has been paid to the studies describing the
toxicological profile of PtNPs with an attempt to draw critical conclusions. The
emerging picture suggests that the material per se is not causing cytotoxicity,
while other physicochemical features related to the synthesis and surface
functionalization may play a crucial role in determining the observed impairment
of cellular functions. The enzymatic activity of PtNPs is also summarized,
analyzing their action against ROS produced by pathological conditions within the
cells. In particular, we extensively discuss the potential of these properties in
nanomedicine to down-regulate inflammatory pathways or to be employed as
diagnostic tools with colorimetric readout. A brief overview of other biomedical
applications of nanoplatinum is also presented.
PMID- 28696453
TI - A tactile sensor using single layer graphene for surface texture recognition.
AB - Tactile sensors capable of texture recognition are essential for artificial skin
functions. In this work, we describe a tactile sensor with a single sensor
architecture made of single layer graphene that can recognize surface texture
based on the roughness of the interacting surface. Resistance changes due to the
local deformation of a local area of the single layer graphene are reflected in
the resistance of the entire sensor. By introducing microstructures inspired by
human finger prints, surface texture was successfully defined through fast
Fourier transform analysis, and spatial resolution was easily achievable. This
work provides a simple method utilizing a single sensor for surface texture
recognition at the level of human sensation without using a matrix architecture
which requires high density integration technology with force and vibration
sensor elements.
PMID- 28696454
TI - A cation-exchange controlled core-shell MnS@Bi2S3 theranostic platform for
multimodal imaging guided radiation therapy with hyperthermia boost.
AB - Overtreatment as a crucial modern medicine issue needs to be urgently addressed.
Theranostic agents supply a unique platform and integrate multiple diagnosis and
therapies to deal with this issue. In this study, a core-shell MnS@Bi2S3
nanostructure was fabricated via two step reactions for tri-modal imaging guided
thermo-radio synergistic therapy. The mass ratio between the core and shell of
the constructed MnS@Bi2S3 can be precisely controlled via cation exchange
reaction. After surface PEGylation, MnS@Bi2S3-PEG nanoparticles exhibited
excellent aqueous medium dispersibility for bioapplications. Based on the r1 and
r2 relaxivity obtained from the MnS core and the strong near-infrared absorption
and X-ray attenuation abilities of the Bi2S3 shell, the intratumoral injected
MnS@Bi2S3-PEG can realize in vivo magnetic resonance, computer tomography, and
photoacoustic tumor imaging under a single injection dose. Hyperthermia
significantly boosts the efficacy of radiation therapy, showing synergistic tumor
treatment efficacy. No obvious toxicity is monitored for the treated mice. Our
study not only provides a new way to precisely construct the core-shell
nanocomposite, but also presents a unique theranostic platform and unifies the
solutions for the challenges related with high injection dose and overtreatment.
PMID- 28696455
TI - Origin of highly efficient photoluminescence in AgIn5S8 nanoparticles.
AB - The photoluminescence of AgIn5S8 nanoparticles was examined to clarify the
emissive relaxation processes of defect states and to explain the highly
efficient photoluminescence of defect states. The large Stokes shift of the
defect emission was explained by strong electron-phonon coupling in the
nanoparticles. Steady-state and time-resolved photoluminescence spectroscopy
indicated two emissive defect states with characteristic emission energies and
lifetimes. Change of the surface-to-volume ratio in the nanoparticles affected
the relative contribution of the two states, implying that defect emission in
higher energy was attributable to surface-related defects. The defect emission in
lower energy was attributable to intrinsic defects, which were also present in
bulk. The quantum yield of the surface defects was larger than that of the
intrinsic defects, which accounted for the unusually high quantum yield of
AgIn5S8 nanoparticles, although the origin of emission was the defect states, not
the exciton recombination found in typical semiconductor nanoparticles.
PMID- 28696456
TI - Pt nanocrystals on nitrogen-doped graphene for the hydrogen evolution reaction
using Si nanowires as a sacrificial template.
AB - Cost-effective catalysts for electrocatalytic water splitting play a key role in
the renewable energy research. Although Pt has been regarded as the best
catalyst, its wide applications have been impeded by its high cost and scarce
natural abundance. Therefore, decreasing the Pt usage for electrocatalyst design
is significant toward the hydrogen evolution reaction (HER). Herein, flower-like
Pt nanocrystals were loaded on the surface of nitrogen-doped graphene using Si
nanowires as the sacrificial template. The experimental results showed that the
optimal Pt nanocrystals/N-doped graphene with superior HER activity and excellent
stability only has a low Pt loading of 5.0 wt%. It is noted that the HER mass
activity of the Pt nanocrystals/N-doped graphene is 5 fold higher than that of
the 20.0 wt% Pt/C commercial catalyst. This optimal catalyst also achieved a low
Tafel slope (28.0 mV dec-1), large apparent exchange current density (0.989 mA cm
2) and high turnover frequency (2.05 s-1). This work may provide an effective
avenue for developing highly efficient electrochemical catalysts for the HER.
PMID- 28696457
TI - Control of the light-response in supramolecular metallopolymeric gels by tuning
the coordination metal.
AB - Two novel supramolecular metallo-heteropolymers bearing a photo-isomerizable
telechelic bis-terpyridine ligand and either Fe(ii) or Co(ii) coordination metal
were synthesized. Both polymers induced gelation of organic solvents at a
concentration as low as 0.12 wt% yielding thixotropic gels. Judicious choice of
the electronic and photophysical properties of both ditopic ligand and metal ion
enabled to achieve control over photomechanical response in supramolecular
organogels upon UV light irradiation through molecular design.
PMID- 28696458
TI - Effect of the cation on the stability of cation-glyme complexes and their
interactions with the [TFSA]- anion.
AB - The interactions of glymes with alkali or alkaline earth metal cations depend
strongly on the metal cations. For example, the stabilization energies (Eform)
calculated for the formation of cation-triglyme (G3) complexes with Li+, Na+, K+,
Mg2+, and Ca2+ at the MP2/6-311G** level were -95.6, -66.4, -52.5, -255.0, and
185.0 kcal mol-1, respectively, and those for the cation-tetraglyme (G4)
complexes were -107.7, -76.3, -60.9, -288.3 and -215.0 kcal mol-1, respectively.
The electrostatic and induction interactions are the major source of the
attraction in the complexes; the contribution of the induction interactions to
the attraction is especially significant in the divalent cation-glyme complexes.
The binding energies of the cation-G3 complexes with Li+, Na+, K+, Mg2+, and Ca2+
and the bis(trifluoromethylsulfonyl)amide anion ([TFSA]-) were -83.9, -86.6,
80.0, -196.1, and -189.5 kcal mol-1, respectively, and they are larger than the
binding energies of the corresponding cation-G4 complexes (-73.6, -75.0, -77.4,
172.1, and -177.2 kcal mol-1, respectively). The binding energies and
conformational flexibility of the cation-glyme complexes also affect the melting
points of equimolar mixtures of glyme and TFSA salts. Furthermore, the
interactions of the metal cations with the oxygen atoms of glymes significantly
decrease the HOMO energy levels of glymes. The HOMO energy levels of glymes in
the cation-glyme-TFSA complexes are lower than those of isolated glymes, although
they are higher than those of the cation-glyme complexes.
PMID- 28696459
TI - The origin of the Debye relaxation in liquid water and fitting the high frequency
excess response.
AB - We critically review the literature on the Debye absorption peak of liquid water
and the excess response found on the high frequency side of the Debye peak. We
find a lack of agreement on the microscopic phenomena underlying both of these
features. To better understand the molecular origin of Debye peak we ran large
scale molecular dynamics simulations and performed several different distance
dependent decompositions of the low frequency dielectric spectra, finding that it
involves processes that take place on scales of 1.5-2.0 nm. We also calculated
the k-dependence of the Debye relaxation, finding it to be highly dispersive.
These findings are inconsistent with models that relate Debye relaxation to local
processes such as the rotation/translation of molecules after H-bond breaking. We
introduce the spectrumfitter Python package for fitting dielectric spectra and
analyze different ways of fitting the high frequency excess, such as including
one or two additional Debye peaks. We propose using the generalized Lydanne-Sachs
Teller (gLST) equation as a way of testing the physicality of model dielectric
functions. Our attempts at fitting the experimental spectrum using the gLST
relation as a constraint indicate that the traditional way of fitting the excess
response with secondary and tertiary Debye relaxations is problematic. All of our
work is consistent with the recent theory of Popov et al. (2016) that Debye
relaxation is due to the migration of Bjerrum-like defects in the hydrogen bond
network. Under this theory, the mechanism of Debye relaxation in liquid water is
similar to the mechanism in ice, but the heterogeneity and power-law dynamics of
the H-bond network in water results in excess response on the high frequency side
of the peak.
PMID- 28696460
TI - Mesoporous semiconducting TiO2 with rich active sites as a remarkable substrate
for surface-enhanced Raman scattering.
AB - Recently, surface-enhanced Raman scattering (SERS) research based on
semiconductor TiO2 has received increasing attention. However, the practical
application of TiO2 SERS-active substrates has been hampered due to their lower
surface performance and detection sensitivity. Here we report a new strategy to
enhance the SERS activity of TiO2 nanoparticles (NPs) by means of formation of a
mesoporous framework via reductive calcination of polymer coated nanocrystals.
The 4-mercaptobenzoic acid (4-MBA) probe molecules on the mesoporous TiO2
substrate exhibit larger SERS enhancement compared with that on the ordinary TiO2
NP substrate; this considerable SERS enhancement mainly stems from the
contributions of rich surface active sites of mesoporous TiO2, which can provide
more effective adsorption sites for the molecules and promote the charge transfer
between the substrate and the adsorbed molecule, and thus remarkably enhance SERS
signals. On the mesoporous TiO2, a detection limit of 4-MBA as low as 1 * 10-8
mol L-1 can be achieved, which is the highest sensitivity among those reported
for semiconducting substrates and even comparable with those of noble metal
substrates. And, it is proved that the mesoporous TiO2 substrates are
characterized by high stability and self-cleaning properties, and can be
repeatedly used in SERS detection without losing their activity.
PMID- 28696461
TI - Room-temperature in-cell EPR spectroscopy: alpha-Synuclein disease variants
remain intrinsically disordered in the cell.
AB - Human alpha-Synuclein (aS), implicated in Parkinson's disease, adopts a rich
variety of different conformations depending on the macromolecular context. In
order to unravel its pathophysiological role, monitoring its intracellular
conformational state and identifying differences for the disease variants is
crucial. Here, we present an intracellular spectroscopy approach based on a
systematic spin-labeling site-scan in combination with intracellular electron
paramagnetic resonance spectroscopy determining conformations on a molecular
scale. A quantitative and model-based data analysis revealed that the vast
majority of aS, be it wild-type or disease variants A30P or A53T, exists in the
monomeric intrinsically disordered form in the cell.
PMID- 28696462
TI - One-pot synthesis of Co/N-doped mesoporous graphene with embedded Co/CoOx
nanoparticles for efficient oxygen reduction reaction.
AB - Exploration of sustainable electrocatalysts toward oxygen reduction reaction
(ORR) with high catalytic activity remains a key challenge in the development of
metal-air batteries and fuel cells. In this work, a hybrid electrocatalyst
composed of cobalt (Co/CoOx) nanoparticles encapsulated in Co/N-doped mesoporous
graphene (Co/CoOx@Co/N-graphene) is reported for efficient ORR catalysis. The
catalyst is rationally designed and synthesized via a facile combination of
spontaneous one-pot polymerization of dopamine in the presence of graphene oxide
(GO) and Co2+ ions and the subsequent carbonization process. The morphology,
doping nature and ORR activity of the as-prepared catalyst are systematically
investigated. It is found that there are abundant Co/N active sites and Co/CoOx
nanoparticles in this hybrid catalyst, leading to a synergistic enhancement
effect for improved ORR activity. In an alkaline environment, this Co/CoOx@Co/N
graphene catalyst displays Pt/C-comparable ORR activity in terms of half-wave
potential and four-electron reduction selectivity, and higher limiting current
density, better methanol tolerant ability and long-term durability. When being
evaluated in a Zn-air battery, it demonstrates superior performance to the
commercial Pt/C catalyst.
PMID- 28696463
TI - Xanthine oxidase-product complexes probe the importance of substrate/product
orientation along the reaction coordinate.
AB - A combination of reaction coordinate computations, resonance Raman spectroscopy,
spectroscopic computations, and hydrogen bonding investigations have been used to
understand the importance of substrate orientation along the xanthine oxidase
reaction coordinate. Specifically, 4-thiolumazine and 2,4-dithiolumazine have
been used as reducing substrates for xanthine oxidase to form stable enzyme
product charge transfer complexes suitable for spectroscopic study. Laser
excitation into the near-infrared molybdenum-to-product charge transfer band
produces rR enhancement patterns in the high frequency in-plane stretching region
that directly probe the nature of this MLCT transition and provide insight into
the effects of electron redistribution along the reaction coordinate between the
transition state and the stable enzyme-product intermediate, including the role
of the covalent Mo-O-C linkage in facilitating this process. The results clearly
show that specific Mo-substrate orientations allow for enhanced electronic
coupling and facilitate strong hydrogen bonding interactions with amino acid
residues in the substrate binding pocket.
PMID- 28696464
TI - Density-tunable lightweight polymer composites with dual-functional ability of
efficient EMI shielding and heat dissipation.
AB - Lightweight dual-functional materials with high EMI shielding performance and
thermal conductivity are of great importance in modern cutting-edge applications,
such as mobile electronics, automotive, aerospace, and military. Unfortunately, a
clear material solution has not emerged yet. Herein, we demonstrate a simple and
effective way to fabricate lightweight metal-based polymer composites with dual
functional ability of excellent EMI shielding effectiveness and thermal
conductivity using expandable polymer bead-templated Cu hollow beads. The low
density Cu hollow beads (rho ~ 0.44 g cm-3) were fabricated through electroless
plating of Cu on the expanded polymer beads with ultralow density (rho ~ 0.02 g
cm-3). The resulting composites that formed a continuous 3D Cu network with a
very small Cu content (~9.8 vol%) exhibited excellent EMI shielding (110.7 dB at
7 GHz) and thermal conductivity (7.0 W m-1 K-1) with isotropic features.
Moreover, the densities of the composites are tunable from 1.28 to 0.59 g cm-3 in
accordance with the purpose of their applications. To the best of our knowledge,
the resulting composites are the best lightweight dual-functional materials with
exceptionally high EMI SE and thermal conductivity performance among synthetic
polymer composites.
PMID- 28696465
TI - Novel red-emitting phosphors A2HfF6:Mn4+ (A = Rb+, Cs+) for solid-state lighting.
AB - New red-emitting phosphors A2HfF6:Mn4+ (A = Rb+, Cs+) with a single phase have
been successfully synthesized via a simple ion exchange method, and their
structures and luminescence properties were investigated. It was found that Mn4+
ions in Rb2HfF6 and Cs2HfF6 who share wide band gaps can possess broad excitation
bands in the blue regions and intense red emission with internal quantum yields
of 0.556 and 0.652, respectively. Meanwhile, these red phosphors exhibit high
chemical and thermal stabilities. A series of LED devices with a tunable color
rendering index and color temperature were fabricated with these samples which
can remarkably optimize the optical performances of white light-emitting diodes
(w-LEDs). These results indicate that A2HfF6:Mn4+ phosphors can be promising red
phosphors in w-LEDs.
PMID- 28696467
TI - Top-down and bottom-up approaches to transparent, flexible and luminescent
nitrogen-doped carbon nanodot-clay hybrid films.
AB - Two easy approaches are successfully employed for the preparation of nitrogen
doped carbon nanodot (NCND)-clay hybrids (bulk solids and thin films).
Fluorescent and small NCNDs are intercalated within the interlayer space of
LAPONITE(r) clay with a simple ion exchange reaction in bulk or embedded between
functionalized LAPONITE(r) sheets by combining a layer-by-layer approach with a
self-assembly process. In both cases, homogeneous hybrids with 2D-ordered NCNDs
(accounting for >20 wt%) are produced, with the NCND optoelectronic properties
preserved. Drop casting of suspensions or self-assembly on flexible substrates
allows the fabrication of luminescent flexible films. The transparency of the
films is found to be adjustable either by controlling the concentration of the
drop-cast suspensions or by the number of layers in the self-assembly procedure.
The prepared films are stable over time: the inert LAPONITE(r) platelets not only
guide the highly ordered 2D assemblies of NCNDs in the interlayer space but also
protect them from external agents, which could affect their surfaces and thus
alter their optoelectronic properties.
PMID- 28696468
TI - The effect of probe choice and solution conditions on the apparent
photoreactivity of dissolved organic matter.
AB - Excited triplet states of dissolved organic matter (3DOM) are quantified directly
with the species-specific probes trans,trans-hexadienoic acid (HDA) and 2,4,6
trimethylphenol (TMP), and indirectly with the singlet oxygen (1O2) probe
furfuryl alcohol (FFA). Although previous work suggests that these probe
compounds may be sensitive to solution conditions, including dissolved organic
carbon concentration ([DOC]) and pH, and may quantify different 3DOM
subpopulations, the probes have not been systematically compared. Therefore, we
quantify the apparent photoreactivity of diverse environmental waters using HDA,
TMP, and FFA. By conducting experiments under ambient [DOC] and pH, with
standardized [DOC] and pH, and with solid phase extraction isolates, we
demonstrate that much of the apparent dissimilarity in photochemical measurements
is attributable to solution conditions, rather than intrinsic differences in 3DOM
production. In general, apparent quantum yields (Phi1O2 >= Phi3DOM,TMP ?
Phi3DOM,HDA) and pseudo-steady state concentrations ([1O2]ss > [3DOM]ss,TMP >
[3DOM]ss,HDA) show consistent relationships in all waters under standardized
conditions. However, intrinsic differences in 3DOM photoreactivity are apparent
between DOM from diverse sources, as seen in the higher Phi1O2 and lower
Phi3DOM,TMP of wastewater effluents compared with oligotrophic lakes.
Additionally, while conflicting trends in photoreactivity are observed under
ambient conditions, all probes observe quantum yields increasing from surface
wetlands to terrestrially influenced waters to oligotrophic lakes under
standardized conditions. This work elucidates how probe selection and solution
conditions influence the apparent photoreactivity of environmental waters and
confirms that 3DOM or 1O2 probes cannot be used interchangeably in waters that
vary in [DOC], pH, or DOM source.
PMID- 28696469
TI - Band structure modification of the thermoelectric Heusler-phase TiFe2Sn via Mn
substitution.
AB - Doping (or substitution)-induced modification of the electronic structure to
increase the electronic density of states (eDOS) near the Fermi level is
considered as an effective strategy to enhance the Seebeck coefficient, and may
consequently boost the thermoelectric performance. Through density-functional
theory calculations of Mn-substituted TiFe2-xMnxSn compounds, we demonstrate that
the d-states of the substituted Mn atoms induce a strong resonant level near the
Fermi energy. Our experimental results are in good agreement with the
calculations. They show that Mn substitution results in a large increase of the
Seebeck coefficient, arising from an enhanced eDOS in Heusler compounds. The
results prove that a proper substitution position and element selection can
increase the eDOS, leading to a higher Seebeck coefficient and thermoelectric
performance of ecofriendly materials.
PMID- 28696470
TI - The impact of chemical structure and molecular packing on the electronic
polarisation of fullerene arrays.
AB - Electronic polarisation contributes to the electronic landscape as seen by
separating charges in organic materials. The nature of electronic polarisation
depends on the polarisability, density, and arrangement of polarisable molecules.
In this paper, we introduce a microscopic, coarse-grained model in which we treat
each molecule as a polarisable site, and use an array of such polarisable dipoles
to calculate the electric field and associated energy of any arrangement of
charges in the medium. The model incorporates chemical structure via the
molecular polarisability and molecular packing patterns via the structure of the
array. We use this model to calculate energies of charge pairs undergoing
separation in finite fullerene lattices of different chemical and crystal
structures. The effective dielectric constants that we estimate from this
approach are in good quantitative agreement with those measured experimentally in
C60 and phenyl-C61-butyric acid methyl ester (PCBM) films, but we find
significant differences in dielectric constant depending on packing and on
direction of separation, which we rationalise in terms of density of polarisable
fullerene cages in regions of high field. In general, we find lattices containing
molecules of more isotropic polarisability tensors exhibit higher dielectric
constants. By exploring several model systems we conclude that differences in
molecular polarisability (and therefore, chemical structure) appear to be less
important than differences in molecular packing and separation direction in
determining the energetic landscape for charge separation. We note that the
results are relevant for finite lattices, but not necessarily for infinite
systems. We propose that the model could be used to design molecular systems for
effective electronic screening.
PMID- 28696471
TI - The temperature behavior and mechanism of exciton luminescence in quantum dots.
AB - The processes of direct and indirect optical excitation of spatially confined
excitons in quantum dots (QDs) embedded in a silica thin-film matrix have been
reported and discussed. A generalized scheme for the electronic transitions is
employed for a detailed description of luminescence temperature behavior using
various excitation methods. This scheme considers three different models of
exciton relaxation and substantiates the occupation of the triplet radiative
states as a result of singlet-triplet intersystem crossing or excitation energy
transfer from free excitons of the matrix. Analytical expressions describing five
types of different temperature curves were derived. It is established that their
shapes are exactly defined by the excitation mechanism and the parameters
involved in the numerical model. The conditions allowing the estimation of the
energy and kinetic characteristics of QD photoluminescence are formulated. We
have shown that the confinement effect causes a decrease in the thermal
activation barriers and frequency characteristics for non-radiative transitions.
An application of the developed concepts allows predicting and estimating the
temperature dependences for direct and indirect optically excited QD luminescence
employing silicon nanoclusters in a silica thin-film matrix as an example.
PMID- 28696472
TI - Urchin-like NiCo2O4 nanoneedles grown on mesocarbon microbeads with synergistic
electrochemical properties as electrodes for symmetric supercapacitors.
AB - Here, we report a facile method to fabricate NiCo2O4 nanoneedles on mesocarbon
microbeads (MCMB) and form a unique urchin-like core-shell structure. In this
composite, the MCMB not only provided high conductivity to benefit effective
electron transfer, but also offered abundant adsorption points to load the
NiCo2O4 nanoneedles. The aggregation of the NiCo2O4 nanoneedles was therefore
alleviated and each NiCo2O4 grain was unfolded to gain easy access to the
electrolyte for efficient ion transfer. When the NiCo2O4@MCMB composite was
evaluated as an electrode material for supercapacitors, a synergistic effect was
exerted with high specific capacitance (458 F g-1 at 1 A g-1) and large
reversibility (116% capacitance retention after 3000 cycles), both of which were
of great advantage over individual MCMB and NiCo2O4 nanoneedles. The NiCo2O4@MCMB
was also used to construct a symmetric supercapacitor, which showed enlarged
voltage profiles and could light the LED device for a few minutes, further
confirming its excellent electrochemical performance.
PMID- 28696473
TI - Halogenation dictates the architecture of amyloid peptide nanostructures.
AB - Amyloid peptides yield a plethora of interesting nanostructures though difficult
to control. Here we report that depending on the number, position, and nature of
the halogen atoms introduced into either one or both phenylalanine benzene rings
of the amyloid beta peptide-derived core-sequence KLVFF, four different
architectures were obtained in a controlled manner. Our findings demonstrate that
halogenation may develop as a general strategy to engineer amyloidal peptide self
assembly and obtain new amyloidal nanostructures.
PMID- 28696474
TI - Primary photochemical processes for Pt(iv) diazido complexes prospective in
photodynamic therapy of tumors.
AB - Diazide diamino complexes of Pt(iv) are considered as prospective prodrugs in
oxygen-free photodynamic therapy (PDT). Primary photophysical and photochemical
processes for cis,trans,cis-[Pt(N3)2(OH)2(NH3)2] and trans,trans,trans
[Pt(N3)2(OH)2(NH3)2] complexes were studied by means of stationary photolysis,
nanosecond laser flash photolysis and ultrafast kinetic spectroscopy. The process
of photolysis is multistage. The first stage is the photosubstitution of an azide
ligand to a water molecule. This process was shown to be a chain reaction
involving redox stages. Pt(iv) and Pt(iii) intermediates responsible for the
chain propagation were recorded using ultrafast kinetic spectroscopy and
nanosecond laser flash photolysis. The mechanism of photosubstitution is
proposed.
PMID- 28696476
TI - On the origin of the driving force in the Marangoni propelled gas bubble trapping
mechanism.
AB - Gas bubbles can be trapped and then manipulated with laser light. In this report,
we propose the detailed optical trapping mechanism of gas bubbles confined inside
a thin light-absorbing liquid layer between two glass plates. The necessary
condition of bubble trapping in this case is the direct absorption of light by
the solution containing a dye. Due to heat release, fluid whirls propelled by the
surface Marangoni effect at the liquid/gas interface emerge and extend to large
distances. We report the experimental microscopic observation of the origin of
whirls at an initially flat liquid/air interface as well as at the curved
interface of a liquid/gas bubble and support this finding with advanced numerical
simulations using the finite element method within the COMSOL Multiphysics
platform. The simulation results were in good agreement with the observations,
which allowed us to propose a simple physical model for this particular trapping
mechanism, to establish the origin of forces attracting bubbles toward a laser
beam and to predict other phenomena related to this effect.
PMID- 28696477
TI - The underlying factors controlling the Pd-catalyzed site-selective alkenylation
of aliphatic amines.
AB - The Pd(ii)-catalyzed site-selective delta-C(sp3)-H alkenylation in the presence
of more accessible gamma-C(sp3)-H bonds is investigated by DFT calculations.
Migratory insertion is found to be both the rate-limiting and the selectivity
determining step. The origin of the unusual site-selectivity is originally
attributed to the different steric repulsion between the alkyne and palladacycle;
however, our theoretical results reveal that the inherent electronic effect
instead of steric repulsion determines the site-selectivity. The proposal is
further validated by model calculations involving the less sterically hindered
1,2-dimethyl acetylene and acetylene. In addition, a novel HCO3--assisted N-H
activation mechanism is reported, and the origin of the regioselectivity of an
unsymmetrical alkyne is also studied.
PMID- 28696478
TI - Unidirectional motion of a camphor disk on water forced by interactions between
surface camphor concentration and dynamically changing boundaries.
AB - We study the motion of a camphor disk on the water surface in a system with
flexible boundaries. The boundaries can be dynamically modified by non-uniform
surface tension resulting from the nonhomogeneous surface concentration of the
camphor molecules dissipated by the disk. We investigate the geometry of the
boundaries that forces unidirectional motion of the disk. The studied system can
be regarded as a signal diode if the presence or absence of a camphor disk at a
specific point is interpreted as the binary TRUE and FALSE variables. The diode
can be incorporated into more complex devices, like a ring that imposes
unidirectional rotation of camphor disks.
PMID- 28696479
TI - A Web-based Game for Teaching Facial Expressions to Schizophrenic Patients.
AB - BACKGROUND: Recognizing facial expressions is an important social skill. In some
psychological disorders such as schizophrenia, loss of this skill may complicate
the patient's daily life. Prior research has shown that information technology
may help to develop facial expression recognition skills through educational
software and games. OBJECTIVES: To examine if a computer game designed for
teaching facial expressions would improve facial expression recognition skills of
patients with schizophrenia. METHODS: We developed a website composed of eight
serious games. Thirty-two patients were given a pre-test composed of 21 facial
expression photographs. Eighteen patients were in the study group while 14 were
in the control group. Patients in the study group were asked to play the games on
the website. After a period of one month, we performed a post-test for all
patients. RESULTS: The median score of the correct answers was 17.5 in the
control group whereas it was 16.5 in the study group (of 21) in pretest. The
median post-test score was 18 in the control group (p=0.052) whereas it was 20 in
the study group (p<0.001). CONCLUSIONS: Computer games may be used for the
purpose of educating people who have difficulty in recognizing facial
expressions.
PMID- 28696480
TI - A Picture is Worth 1,000 Words. The Use of Clinical Images in Electronic Medical
Records.
AB - OBJECTIVE: To understand how clinicians utilize image uploading tools in a home
grown electronic health records (EHR) system. METHODS: A content analysis of
patient notes containing non-radiological images from the EHR was conducted.
Images from 4,000 random notes from July 1, 2009 - June 30, 2010 were reviewed
and manually coded. Codes were assigned to four properties of the image: (1)
image type, (2) role of image uploader (e.g. MD, NP, PA, RN), (3) practice type
(e.g. internal medicine, dermatology, ophthalmology), and (4) image subject.
RESULTS: 3,815 images from image-containing notes stored in the EHR were reviewed
and manually coded. Of those images, 32.8% were clinical and 66.2% were non
clinical. The most common types of the clinical images were photographs (38.0%),
diagrams (19.1%), and scanned documents (14.4%). MDs uploaded 67.9% of clinical
images, followed by RNs with 10.2%, and genetic counselors with 6.8%. Dermatology
(34.9%), ophthalmology (16.1%), and general surgery (10.8%) uploaded the most
clinical images. The content of clinical images referencing body parts varied,
with 49.8% of those images focusing on the head and neck region, 15.3% focusing
on the thorax, and 13.8% focusing on the lower extremities. CONCLUSION: The
diversity of image types, content, and uploaders within a home grown EHR system
reflected the versatility and importance of the image uploading tool.
Understanding how users utilize image uploading tools in a clinical setting
highlights important considerations for designing better EHR tools and the
importance of interoperability between EHR systems and other health technology.
PMID- 28696481
TI - Genome-wide association study of pre-harvest sprouting resistance in Chinese
wheat founder parents.
AB - Pre-harvest sprouting (PHS) is a major abiotic factor affecting grain weight and
quality, and is caused by an early break in seed dormancy. Association mapping
(AM) is used to detect correlations between phenotypes and genotypes based on
linkage disequilibrium (LD) in wheat breeding programs. We evaluated seed
dormancy in 80 Chinese wheat founder parents in five environments and performed a
genome-wide association study using 6,057 markers, including 93 simple sequence
repeat (SSR), 1,472 diversity array technology (DArT), and 4,492 single
nucleotide polymorphism (SNP) markers. The general linear model (GLM) and the
mixed linear model (MLM) were used in this study, and two significant markers
(tPt-7980 and wPt-6457) were identified. Both markers were located on Chromosome
1B, with wPt-6457 having been identified in a previously reported chromosomal
position. The significantly associated loci contain essential information for
cloning genes related to resistance to PHS and can be used in wheat breeding
programs.
PMID- 28696482
TI - Cytotoxicity and genotoxicity of stilbene derivatives in CHO-K1 and HepG2 cell
lines.
AB - The cytotoxicity and genotoxicity of the stilbenes (E)-methyl-4-(3-5
dimethoxystyryl)benzoate (ester), (E)-4-(3-5-dimethoxystyryl)aniline (amino), (Z)
1,3-dimethoxy-5-(4-methoxystyryl)benzene (cis-TMS) and (E)-1,3-dimethoxy-5-(4
methoxystyryl)benzene (trans-TMS) were investigated in this work. Structural
modifications of resveratrol, a naturally occurring stilbene, have been
previously performed, including the replacement of hydroxyl by different
functional groups. Such modifications resulted in significant improvement of
target-specific effects on cell death and antiproliferative responses. The
parameters were evaluated using XTT assay, clonogenic survival assay and the
cytokinesis-block micronucleus assay in CHO-K1 and HepG2 cell lines. The results
showed that cis-TMS is approximately 250-fold more cytotoxic than the amino and
ester, and 128-fold more cytotoxic than trans-TMS. When genotoxicity was
evaluated, only the trans-TMS did not significantly increase the frequency of
micronucleus (MN). While the cis-TMS induced a mean of 5.2 and 5.9 MN/100 cells
at 0.5 MUM in CHO-K1 and HepG2, respectively, the amino and ester induced 3.1 and
3.6 MN/100 cells at 10 MUM in CHO-K1, respectively, and 3.5 and 3.8 in HepG2.
Trans-TMS is genotoxic only in HepG2 cells. Based on these results, the cis-TMS
was the most cytotoxic and genotoxic compound in both cell lines.
PMID- 28696483
TI - Combined Bone Ingrowth and Remodeling Around Uncemented Acetabular Component: A
Multiscale Mechanobiology-Based Finite Element Analysis.
AB - Bone ingrowth and remodeling are two different evolutionary processes which might
occur simultaneously. Both these processes are influenced by local mechanical
stimulus. However, a combined study on bone ingrowth and remodeling has rarely
been performed. This study is aimed at understanding the relationship between
bone ingrowth and adaptation and their combined influence on fixation of the
acetabular component. Based on three-dimensional (3D) macroscale finite element
(FE) model of implanted pelvis and microscale FE model of implant-bone interface,
a multiscale framework has been developed. The numerical prediction of peri
acetabular bone adaptation was based on a strain-energy density-based
formulation. Bone ingrowth in the microscale models was simulated using the
mechanoregulatory algorithm. An increase in bone strains near the acetabular rim
was observed in the implanted pelvis model, whereas the central part of the
acetabulum was observed to be stress shielded. Consequently, progressive bone
apposition near the acetabular rim and resorption near the central region were
observed. Bone remodeling caused a gradual increase in the implant-bone relative
displacements. Evolutionary bone ingrowth was observed around the entire
acetabular component. Poor bone ingrowth of 3-5% was predicted around the centro
inferio and inferio-posterio-superio-peripheral regions owing to higher implant
bone relative displacements, whereas the anterio-inferior and centro-superior
regions exhibited improved bone ingrowth of 35-55% due to moderate implant-bone
relative displacement. For an uncemented acetabular CoCrMo component, bone
ingrowth had hardly any effect on bone remodeling; however, bone remodeling had
considerable influence on bone ingrowth.
PMID- 28696484
TI - Vaginal Changes Due to Varying Degrees of Rectocele Prolapse: A Computational
Study.
AB - Pelvic organ prolapse (POP), downward descent of the pelvic organs resulting in a
protrusion of the vagina, is a highly prevalent condition, responsible for
300,000 surgeries in the U.S. annually. Rectocele, a posterior vaginal wall (PVW)
prolapse of the rectum, is the second most common type of POP after cystocele. A
rectocele usually manifests itself along with other types of prolapse with
multicompartment pelvic floor defects. To date, the specific mechanics of
rectocele formation are poorly understood, which does not allow its early stage
detection and progression prediction over time. Recently, with the advancement of
imaging and computational modeling techniques, a plethora of finite element (FE)
models have been developed to study vaginal prolapse from different perspectives
and allow a better understanding of dynamic interactions of pelvic organs and
their supporting structures. So far, most studies have focused on anterior
vaginal prolapse (AVP) (or cystocele) and limited data exist on the role of
pelvic muscles and ligaments on the development and progression of rectocele. In
this work, a full-scale magnetic resonance imaging (MRI) based three-dimensional
(3D) computational model of the female pelvic anatomy, comprising the vaginal
canal, uterus, and rectum, was developed to study the effect of varying degrees
(or sizes) of rectocele prolapse on the vaginal canal for the first time. Vaginal
wall displacements and stresses generated due to the varying rectocele size and
average abdominal pressures were estimated. Considering the direction pointing
from anterior to posterior side of the pelvic system as the positive Y-direction,
it was found that rectocele leads to negative Y-direction displacements, causing
the vaginal cross section to shrink significantly at the lower half of the
vaginal canal. Besides the negative Y displacements, the rectocele bulging was
observed to push the PVW downward toward the vaginal hiatus, exhibiting the well
known "kneeling effect." Also, the stress field on the PVW was found to localize
at the upper half of the vaginal canal and shift eventually to the lower half
with increase in rectocele size. Additionally, clinical relevance and
implications of the results were discussed.
PMID- 28696485
TI - Repeatability of a Dislocation Spinal Cord Injury Model in a Rat-A High-Speed
Biomechanical Analysis.
AB - Dislocation is the most common, and severe, spinal cord injury (SCI) mechanism in
humans, yet there are few preclinical models. While dislocation in the rat model
has been shown to produce unique outcomes, like other closed column models it
exhibits higher outcome variability. Refinement of the dislocation model will
enhance the testing of neuroprotective strategies, further biomechanical
understanding, and guide therapeutic decisions. The overall objective of this
study is to improve biomechanical repeatability of a dislocation SCI model in the
rat, through the following specific aims: (i) design new injury clamps that pivot
and self-align to the vertebrae; (ii) measure intervertebral kinematics during
injury using the existing and redesigned clamps; and (iii) compare relative
motion at the vertebrae-clamp interface to determine which clamps provide the
most rigid connection. Novel clamps that pivot and self-align were developed
based on the quantitative rat vertebral anatomy. A dislocation injury was
produced in 34 rats at C4/C5 using either the existing or redesigned clamps, and
a high-speed X-ray device recorded the kinematics. Relative motion between the
caudal clamp and C5 was significantly greater in the existing clamps compared to
the redesigned clamps in dorsoventral translation and sagittal rotation. This
study demonstrates that relative motions can be of magnitudes that likely affect
injury outcomes. We recommend such biomechanical analyses be applied to other SCI
models when repeatability is an issue. For this dislocation model, the results
show the importance of using clamps that pivot and self-align to the vertebrae.
PMID- 28696486
TI - Modeling Wheelchair-Users Undergoing Vibrations.
AB - A procedure for modeling wheelchair-users undergoing vibrations was developed.
Experimental data acquired with a wheelchair simulator were used to develop a
model of a seated wheelchair user. Maximum likelihood estimation procedure was
used to determine the model complexity required to characterize wheelchair-user's
response. It was determined that a two segment rotational link model is adequate
for characterization of vibratory response. The parameters of the proposed model
were identified using the experimental data and verified using additional
experimental results. The proposed approach can be used to develop subject
specific design criteria for wheelchair seating and suspension.
PMID- 28696487
TI - ?
PMID- 28696488
TI - ?
PMID- 28696489
TI - ?
PMID- 28696490
TI - ?
PMID- 28696491
TI - ?
PMID- 28696492
TI - Trocar Site Hernia After Gastric Bypass.
AB - BACKGROUND: The 5.2% rate of trocar site incisional hernia (TSIH) reported
appears low in view of the proportion of TSIH repairs being performed. Detecting
TSIH by clinical examination may be difficult in the obese. The correlation
between clinical examination and a novel radiological examination for the
detection of TSIH in obese patients was studied. MATERIALS AND METHODS: Twenty
six patients subjected to laparoscopic gastric bypass in 2010 underwent clinical
and radiological examination by three independent assessors for each method,
after a mean follow-up time of 33 months. The computed tomography was in the
prone position upon a ring. RESULTS: At clinical examination, a TSIH was regarded
to be present in six out of 26 patients and at CT scan in four. The Fleiss' Kappa
for multiple raters was 0.40 (p = 0.184) with clinical examination and 1 (p
<0.05) with CT scan. With CT scan, herniation was diagnosed in three of 26
umbilical trocar sites that had been closed at the index operation, and in one of
the 130 other trocar sites that had not been closed. CONCLUSIONS: Clinical
examination is not reliable when detecting TSIH in the obese. A CT scan in the
prone position was extremely reliable and seems to have the potential of becoming
the standard method for detecting TSIH in obese patients.
PMID- 28696493
TI - Total Contact Cast System to Heal Diabetic Foot Ulcers.
AB - Off-loadinga diabetic foot ulcer is a cornerstone of quality wound care for
diabetic patients to allow cellular growth in the wound bed. While total contact
casts (TCC) have been described as the gold standard for off-loading the wound,
the complexity of application and the time commitment for both application and
drying have discouraged health professionals from using them. This retrospective
case series, conducted in a podiatric practice, evaluated using a TCC system that
helps address the three components in which guidelines should be addressed when
caring for a diabetic foot: V - vascular management, I - infection management and
prevention, and P - pressure relief. This studied TCC system can be applied in
approximately seven minutes and the patient can ambulate immediately without
waiting for drying. Of the 20 wounds treated with this TCC, 18/20 (90%) healed in
a mean of 22.3 days. The mean number of TCC treatments was 2.8. When compared to
evidence published in the scientific literature documenting healing outcomes
using various TCCs, this system has the fastest observational healing rate. In
this case series, this TCC system for off-loading was found to be clinically
beneficial for the patient in a physician's office practice.
PMID- 28696494
TI - Cryotherapy Treatment After Arthroscopic Knee Debridement and ACL Reconstruction:
A Review.
AB - Pain, swelling, and inflammation of the knee joint and its surrounding soft
tissue structures are common during the postoperative period after arthroscopic
knee debridement and anterior cruciate ligament reconstruction. These challenges
can make patient recovery difficult immediately after surgery. Several options
exist, however, to help patients overcome these challenges. Cryotherapy has been
noted to decrease pain, swelling, and inflammation. However, while a number of
studies exist characterizing the use of cryotherapy after knee surgery, no
definitive cryotherapy devices and modalities have been identified. Therefore,
the purpose of this review was to evaluate randomized controlled trials to assess
the use of cryotherapy after: 1) arthroscopic debridement; and 2) anterior
cruciate ligament reconstruction.
PMID- 28696495
TI - Robotic-Arm Assisted Total Knee Arthroplasty Demonstrated Soft Tissue Protection.
AB - INTRODUCTION: While total knee arthroplasty (TKA) procedures have demonstrated
clinical success, occasionally intraoperative complications can occur. Collateral
or posterior cruciate ligament injury, instability, extensor mechanism
disruption, and tibiofemoral or patellofemoral dislocation are among a few of the
intraoperatively driven adverse events prevalently ranked by The Knee Society.
Robotic-arm assisted TKA (RATKA) provides a surgeon the ability to three
dimensionally plan a TKA and use intraoperative visual, auditory, and tactile
feedback to ensure that only the desired bone cuts are made. The potential
benefits of soft tissue protection in these surgeries need to be further
evaluated. The purpose of this cadaver study was to assess the a) integrity of
various knee soft tissue structures (medial collateral ligament [MCL], lateral
collateral ligament [LCL], posterior cruciate ligament [PCL], and the patellar
ligament), as well as b) the need for tibial subluxation and patellar eversion
during RATKA procedures. MATERIALS AND METHODS: Six cadaver knees were prepared
using RATKA by a surgeon with no prior clinical robotic experience. These were
compared to seven manually performed cases as a control. The mean Kellgren
Lawrence score was 2.8 (range, 0 to 4) in RATKA and 2.6 (range, 1 to 4) in the
manual cohort. The presence of soft tissue damage was assessed by having an
experienced surgeon perform a visual evaluation and palpation of the PCL, MCL,
LCL, and the patellar ligament after the procedures. In addition, leg pose and
retraction were documented during all bone resections. The amount of tibial
subluxation and patellar eversion was recorded for each case. RESULTS: For all
RATKA-assisted cases, there was no visible evidence of disruption of any of the
ligaments. All RATKA cases were left with a bone island on the tibial plateau,
which protected the PCL. Tibial subluxation and patella eversion were not
required for visualization in any RATKA cases. In two of the seven MTKA cases,
there was slight disruption noted of the PCL, although this did not lead to any
apparent change in the functional integrity of the ligament. All MTKA cases
required tibial subluxation and patellar revision to achieve optimal
visualization. DISCUSSION: Several aspects of soft tissue protection were noted
during the study. During bone resections, the tibia in RATKA procedures did not
require subluxation, which may reduce ligament stretching or decrease
complication rates. Potential patient benefits for short-term recovery and
decreased morbidity to reduce operative complications should be studied in a
clinical setting. Since RATKA uses a stereotactic boundary to constrain the
sawblade, which is generated based on the implant size, shape, and plan, and does
not have the ability to track the patient's soft tissue structures, standard
retraction techniques during cutting are recommended. Therefore, the retractor
placement and potential for soft tissue protection needs to be further
investigated. RATKA has the potential to increase soft tissue protection when
compared to manual TKA.
PMID- 28696496
TI - Commentary on: "A Cadaver Study to Evaluate the Accuracy of a New 3D Mini-optical
Navigation Tool for Total Hip Arthroplasty".
PMID- 28696497
TI - Role of Ca2+ and ion channels in the regulation of apoptosis under hypoxia.
AB - Hypoxia is a kind of common pathological condition existing in various diseases
such as sleep apnea syndrome, myocardial infarction and stroke, which can
precipitate the onset of diseases through inducing cell apoptosis. Ca2+ is the
ubiquitous message in cell. Given the crucial role of Ca22+ in physiology,
intracellular Ca2+ overload is a significant regulator of apoptosis. Numerous
experiments show that hypoxia may cause changes of multiple cellular Ca2+
channels, for instance, Na+/ Ca2+ Exchanger (NCX), L-type voltage dependent Ca2+
channel (L-VDCC), inositol triphosphate receptors (IP3R) and so on, which
contribute to intracellular Ca2+ overload, thus eventually triggering cell
apoptosis. However, the mechanisms underlying different Ca2+ channels involved in
hypoxic apoptosis are complex. For example, chronic hypoxia or acute hypoxia may
select different Ca2+ channels to influence cell apoptosis. In addition,
intracellular Ca2+ overload may initiate different apoptotic pathways due to
hypoxic duration. Furthermore, different locations in the cell of specific Ca2+
channels activated by hypoxia will determine different apoptosis signaling
pathways. Moreover, activation of different Ca2+ channel isoforms will result in
different outcomes of the cell under hypoxia. Hence, we aim to highlight the
potential mechanisms of the main Ca2+ channels in regulation of apoptosis under
hypoxic stress.
PMID- 28696498
TI - Hsp70 - a master regulator in protein degradation.
AB - Proteostasis, the controlled balance of protein synthesis, folding, assembly,
trafficking and degradation, is a paramount necessity for cell homeostasis.
Impaired proteostasis is a hallmark of ageing and of many human diseases.
Molecular chaperones are essential for proteostasis in eukaryotic cells, and
their function has traditionally been linked to protein folding, assembly and
disaggregation. More recent findings suggest that chaperones also contribute to
key steps in protein degradation. In particular, Hsp70 has an essential role in
substrate degradation through the ubiquitin-proteasome system, as well as through
different autophagy pathways. Accumulated knowledge suggests that the fate of an
Hsp70 substrate is dictated by the combination of partners (cochaperones and
other chaperones) that interact with Hsp70 in a given cell context.
PMID- 28696499
TI - Semihydrogenation of Acetylene on Indium Oxide: Proposed Single-Ensemble
Catalysis.
AB - Indium oxide catalyzes acetylene hydrogenation with high selectivity to ethylene
(>85 %); even with a large excess of the alkene. In situ characterization reveals
the formation of oxygen vacancies under reaction conditions, while an in depth
theoretical analysis links the surface reduction with the creation of well
defined vacancies and surrounding In3 O5 ensembles, which are considered
responsible for this outstanding catalytic function. This behavior, which differs
from that of other common reducible oxides, originates from the presence of four
crystallographically inequivalent oxygen sites in the indium oxide surface. These
resulting ensembles are 1) stable against deactivation, 2) homogeneously and
densely distributed, and 3) spatially isolated and confined against transport;
thereby broadening the scope of oxides in hydrogenation catalysis.
PMID- 28696500
TI - Development of a silicon diode detector for skin dosimetry in radiotherapy.
AB - PURPOSE: The aim of in vivo skin dosimetry was to measure the absorbed dose to
the skin during radiotherapy, when treatment planning calculations cannot be
relied on. It is of particularly importance in hypo-fractionated stereotactic
modalities, where excessive dose can lead to severe skin toxicity. Currently,
commercial diodes for such applications are with water equivalent depths ranging
from 0.5 to 0.8 mm. In this study, we investigate a new detector for skin
dosimetry based on a silicon epitaxial diode, referred to as the skin diode.
METHOD: The skin diode is manufactured on a thin epitaxial layer and packaged
using the "drop-in" technology. It was characterized in terms of percentage depth
dose, dose linearity, and dose rate dependence, and benchmarked against the Attix
ionization chamber. The response of the skin diode in the build-up region of the
percentage depth dose (PDD) curve of a 6 MV clinical photon beam was
investigated. Geant4 radiation transport simulations were used to model the PDD
in order to estimate the water equivalent measurement depth (WED) of the skin
diode. Measured output factors using the skin diode were compared with the MOSkin
detector and EBT3 film at 10 cm depth and at surface at isocenter of a water
equivalent phantom. The intrinsic angular response of the skin diode was also
quantified in charge particle equilibrium conditions (CPE) and at the surface of
a solid water phantom. Finally, the radiation hardness of the skin diode up to an
accumulated dose of 80 kGy using photons from a Co-60 gamma source was evaluated.
RESULTS: The PDD curve measured with the skin diode was within 0.5% agreement of
the equivalent Geant4 simulated curve. When placed at the phantom surface, the
WED of the skin diode was estimated to be 0.075 +/- 0.005 mm from Geant4
simulations and was confirmed using the response of a corrected Attix ionization
chamber placed at water equivalent depth of 0.075 mm, with the measurement
agreement to within 0.3%. The output factor measurements at 10 cm depth were
within 2% of those measured with film and the MOSkin detector down to a field
size of 2 * 2 cm2 . The dose-response for all detector samples was linear and
with a repeatability within 0.2%. The skin diode intrinsic angular response
showed a maximum deviation of 8% at 90 degrees and from 0 to 60 degree is less
than 5%. The radiation sensitivity reduced by 25% after an accumulated dose of 20
kGy but after was found to stabilize. At 60 kGy total accumulated dose the
response was within 2% of that measured at 20 kGy total accumulated dose.
CONCLUSIONS: This work characterizes an innovative detector for in vivo and real
time skin dose measurements that is based on an epitaxial silicon diode combined
with the Centre for Medical Radiation Physics (CMRP) "drop-in" packaging
technology. The skin diode proved to have a water equivalent depth of measurement
of 0.075 +/- 0.005 mm and the ability to measure doses accurately relative to
reference detectors.
PMID- 28696501
TI - Long-term incidence of hysterectomy following endometrial resection or
endometrial ablation for heavy menstrual bleeding.
AB - OBJECTIVE: To estimate the incidence of hysterectomy following endometrial
resection or endometrial ablation (ERA). METHODS: The present retrospective study
enrolled women who underwent ERA for benign heavy menstrual bleeding (HMB) at
Aberdeen Royal Infirmary, UK, between February 1, 1990, and December 31, 1997;
follow-up data to the end of 2015 were included from the pathology laboratory
report system from the single pathology laboratory in the region. Data were
compared between patients who did or did not require a hysterectomy after ERA.
RESULTS: There were 901 patients who underwent ERA for HMB during the study
period. The mean age of patients was 42.3 +/- 5.7 years; of the patients
included, 206 (22.9%) women underwent hysterectomy and these patients had a mean
age of 40.1 years. Of the patients who had hysterectomies, 155 (75.2%) did so in
the first 5 years following ERA, 31 (15.0%) did within 6-10 years, 11 (5.3%) did
within 11-15 years, and 9 (4.4%) did within 16-20 years. In total, 51 (24.8%) of
these patients had hysterectomies within 6-25 years of ERA. CONCLUSIONS: A
significant majority of women who underwent ERA for HMB did not require
hysterectomy up to 25 years after the procedure.
PMID- 28696502
TI - Linking Brain Arteriovenous Malformations With Anorectal Hemorrhoids: A Clinical
and Anatomical Review.
AB - Patients who harbor brain arteriovenous malformations are at risk for
intracranial hemorrhage. These malformations are often seen in inherited vascular
diseases such as hereditary hemorrhagic telangiectasia. However, malformations
within the brain also sporadically occur without a hereditary-coding component.
Here, we review recent insights into the pathophysiology of arteriovenous
malformations, in particular, certain signaling pathways that might underlie
endothelial cell pathology. To better interpret the origins, determinants and
consequences of brain arteriovenous malformations, we present a clinical case to
illustrate the phenotypic landscape of the disease. We also propose that brain
arteriovenous malformations might share certain signaling dimensions with those
of anorectal hemorrhoids. This working hypothesis provides casual anchors from
which to understand vascular diseases characterized by arteriovenous lesions with
a hemorrhagic- or bleeding-risk component. Anat Rec, 2017. (c) The Authors. The
Anatomical Record published by Wiley Periodicals, Inc. on behalf of American
Association of Anatomists. Anat Rec, 300:1973-1980, 2017. (c) 2017 The Authors.
The Anatomical Record published by Wiley Periodicals, Inc. on behalf of American
Association of Anatomists.
PMID- 28696503
TI - Dose-response relationship of a new Timothy grass pollen allergoid in comparison
with a 6-grass pollen allergoid.
AB - BACKGROUND: Subcutaneous allergen immunotherapy with grass pollen allergoids has
been proven to be effective and safe in the treatment of patients with allergic
rhinoconjunctivitis. Based on the extensive cross-reactivity among Pooideae
species, it has been suggested that grass pollen extracts could be prepared from
a single species, rather than from a multiple species mixture. OBJECTIVE: To find
the optimal dose of a Phleum pratense (P. pratense) allergoid preparation and
compare its efficacy and safety to a 6-grass pollen allergoid preparation.
METHODS: In this double-blind, placebo-controlled study (EudraCT: 2011-000674
58), three doses of P. pratense allergoid (1800 therapeutic units (TU), standard
dose 6000 TU and 18 000 TU) were compared with placebo and the marketed 6-grass
pollen allergoid (6000 TU). In a pre-seasonal dosing regimen, 102 patients were
randomized to five treatment groups and received nine subcutaneous injections.
The primary efficacy endpoint was the change in weal size (late-phase reaction
[LPR]) in response to the intracutaneous testing (ICT) before and after
treatment, comparing the active allergoids to placebo. Secondary outcomes were
the change in Total Nasal Symptom Score (TNSS) assessed in the allergen exposure
chamber (AEC), the changes in P. pratense-serum-specific IgG4 and the incidence
of adverse events (AEs). RESULTS: All three doses of the P. pratense and the 6
grass pollen allergoid preparations were significantly superior to placebo for
the primary outcome, whereas there were no significant differences in the change
in TNSS. Compared to the standard-dose, the high-dose of P. pratense did not
produce any additional significant benefit, but showed a slight increase in AEs.
Yet this increase in AEs was lower than for the 6-grass pollen preparation.
CONCLUSIONS & CLINICAL RELEVANCE: The standard-dose of the new P. pratense
allergoid was comparable to the marketed 6-grass pollen preparation at equal dose
for the parameters measured.
PMID- 28696504
TI - Association of MYCN copy number with clinical features, tumor biology, and
outcomes in neuroblastoma: A report from the Children's Oncology Group.
AB - BACKGROUND: High-level MYCN amplification (MNA) is associated with poor outcome
and unfavorable clinical and biological features in patients with neuroblastoma.
To the authors' knowledge, less is known regarding these associations in patients
with low-level MYCN copy number increases. METHODS: In this retrospective study,
the authors classified patients has having tumors with MYCN wild-type tumors,
MYCN gain (2-4-fold increase in MYCN signal compared with the reference probe),
or MNA (>4-fold increase). Tests of trend were used to investigate ordered
associations between MYCN copy number category and features of interest. Log-rank
tests and Cox models compared event-free survival and overall survival by
subgroup. RESULTS: Among 4672 patients, 3694 (79.1%) had MYCN wild-type tumors,
133 (2.8%) had MYCN gain, and 845 (18.1%) had MNA. For each clinical/biological
feature, the percentage of patients with an unfavorable feature was lowest in the
MYCN wild-type category, intermediate in the MYCN gain category, and highest in
the MNA category (P<.0001), except for 11q aberration, for which the highest
rates were in the MYCN gain category. Patients with MYCN gain had inferior event
free survival and overall survival compared with those with MYCN wild-type. Among
patients with high-risk disease, MYCN gain was associated with the lowest
response rate after chemotherapy. Patients with non-stage 4 disease (according to
the International Neuroblastoma Staging System) and patients with non-high-risk
disease with MYCN gain had a significantly increased risk for death, a finding
confirmed on multivariable testing. CONCLUSIONS: Increasing MYCN copy number is
associated with an increasingly higher rate of unfavorable clinical/biological
features, with 11q aberration being an exception. Patients with MYCN gain appear
to have inferior outcomes, especially in otherwise more favorable groups. Cancer
2017;123:4224-4235. (c) 2017 American Cancer Society.
PMID- 28696505
TI - Feelings of indebtedness and guilt toward donor and immunosuppressive medication
adherence among heart transplant (HTx) patients, as assessed in a cross-sectional
study with the Basel Assessment of Adherence to Immunosuppressive Medications
Scale (BAASIS).
AB - BACKGROUND: Nonadherence (NA) to immunosuppressive (IS) medications after organ
transplant is a major risk factor for transplant failure, morbidity, and
treatment costs. This study examined the association between feelings of
indebtedness and guilt toward the donor, and IS medication adherence among HTx
patients. METHODS: In this cross-sectional, descriptive, correlational study, a
convenience sample of 102 HTx patients, from the outpatient facility of a
tertiary medical center in Israel, completed the BAASIS, a validated instrument
for assessing adherence, and reported their feelings of indebtedness and guilt
toward the donor. RESULTS: Missing a dose or skipping two or more doses, taking
medication >2 hours before or after the recommended dosing time, altering the
prescribed amount, or completely stopping the IS treatment in the last 4 weeks,
characterized 64 patients (64%). The highest score received the item "timing
nonadherence," characterizing 58 patients (56.9%). Age, waiting time, and time
since transplant, guilt feelings, and indebtedness to donor explained 17% (R2
=.17) of the variance in adherence (chi2(5) =13.22, P=.021), with age, time since
transplant, and guilt feelings significantly explaining adherence. CONCLUSION:
Physicians and nurses should inquire about the presence of guilt feelings, as
they might be associated with NA to medications after HTx.
PMID- 28696506
TI - Preparation of Acid-Resistant Microcapsules with Shell-Matrix Structure to
Enhance Stability of Streptococcus Thermophilus IFFI 6038.
AB - Microencapsulation is an effective technology used to protect probiotics against
harsh conditions. Extrusion is a commonly used microencapsulation method utilized
to prepare probiotics microcapsules that is regarded as economical and simple to
operate. This research aims to prepare acid-resistant probiotic microcapsules
with high viability after freeze-drying and optimized storage stability.
Streptococcus thermophilus IFFI 6038 (IFFI 6038) cells were mixed with trehalose
and alginate to fabricate microcapsules using extrusion. These capsules were
subsequently coated with chitosan to obtain chitosan-trehalose-alginate
microcapsules with shell-matrix structure. Chitosan-alginate microcapsules
(without trehalose) were also prepared using the same method. The characteristics
of the microcapsules were observed by measuring the freeze-dried viability, acid
resistance, and long-term storage stability of the cells. The viable count of
IFFI 6038 in the chitosan-trehalose-alginate microcapsules was 8.34 +/- 0.30 log
CFU g-1 after freeze-drying (lyophilization), which was nearly 1 log units g-1
greater than the chitosan-alginate microcapsules. The viability of IFFI 6038 in
the chitosan-trehalose-alginate microcapsules was 6.45 +/- 0.09 log CFU g-1 after
120 min of treatment in simulated gastric juices, while the chitosan-alginate
microcapsules only measured 4.82 +/- 0.22 log CFU g-1 . The results of the long
term storage stability assay indicated that the viability of IFFI 6038 in
chitosan-trehalose-alginate microcapsules was higher than in chitosan-alginate
microcapsules after storage at 25 degrees C. Trehalose played an important role
in the stability of IFFI 6038 during storage. The novel shell-matrix chitosan
trehalose-alginate microcapsules showed optimal stability and acid resistance,
demonstrating their potential as a delivery vehicle to transport probiotics.
PMID- 28696507
TI - The impact of epigenomic next-generation sequencing approaches on our
understanding of neuropsychiatric disorders.
AB - Patients suffering from psychiatric disorders have a life span burden, which
represents an enormous human, family, social, and economical cost. Several
concepts have revolutionized our way of appraising neuropsychiatric disorders
(NPDs). They result from a combination of genetic factors and environmental
insults, and their etiology finds roots in the neurodevelopmental period. As
epigenetic mechanisms tightly control brain development, exposure to adverse
conditions disturbing the epigenetic landscape of the fetal brain increases the
risk of developing NPDs, due to the persistence of abnormal epigenetic
signatures, at distance from the initial stimulus. Here, we review these concepts
and discuss recent results based on next-generation sequencing (NGS) approaches
that have shed light on the mechanisms that underlie the emergence of NPDs,
highlighting the importance of epigenetic phenomena. Because epigenetic
mechanisms are potentially reversible, unraveling the epigenetic contribution to
the etiology of NPDs is key to the design of future therapeutic strategies. Early
diagnosis of patients prone to NPDs for early intervention represents a challenge
that waits for biomarkers of vulnerability, and could be decisive for improving
the outcome and prognosis of "at-risk" patients.
PMID- 28696508
TI - Neutrophil extracellular traps in ischemic stroke thrombi.
AB - OBJECTIVE: Neutrophil extracellular traps (NETs) have been shown to promote
thrombus formation. Little is known about the exact composition of thrombi that
cause ischemic stroke. In particular, no information is yet available on the
presence of NETs in cerebral occlusions. Such information is, however, essential
to improve current thrombolytic therapy with tissue plasminogen activator (t-PA).
This study aimed at investigating the presence of neutrophils and more
specifically NETs in ischemic stroke thrombi. METHODS: Sixty-eight thrombi
retrieved from ischemic stroke patients undergoing endovascular treatment were
characterized by immunostaining using neutrophil markers (CD66b and neutrophil
elastase) and NET markers (citrullinated histone H3 [H3Cit] and extracellular
DNA). Neutrophils and NETs were quantified. In addition, extracellular DNA was
targeted by performing ex vivo lysis of retrieved thrombi with DNase 1 and t-PA.
RESULTS: Neutrophils were detected extensively throughout all thrombi. H3Cit, a
hallmark of NETs, was observed in almost all thrombi. H3Cit-positive area varied
up to 13.45% of total thrombus area. Colocalization of H3Cit with extracellular
DNA released from neutrophils confirmed the specific presence of NETs. H3Cit was
more abundant in thrombi of cardioembolic origin compared to other etiologies.
Older thrombi contained significantly more neutrophils and H3Cit compared to
fresh thrombi. Interestingly, ex vivo lysis of patient thrombi was more
successful when adding DNase 1 to standard t-PA. INTERPRETATION: Neutrophils and
NETs form important constituents of cerebral thrombi. Targeting of NETs with
DNase 1 might have prothrombolytic potential in treatment of acute ischemic
stroke. Ann Neurol 2017;82:223-232.
PMID- 28696509
TI - An l-RNA Aptamer with Expanded Chemical Functionality that Inhibits MicroRNA
Biogenesis.
AB - To facilitate isolation of l-aptamers with novel RNA-binding properties, we
employed a cationic nucleotide, 5-aminoallyluridine, during the mirror image in
vitro selection process. Through this effort, we identified a modified l-RNA
aptamer (MlRA) capable of binding oncogenic precursor microRNA 19a (pre-miR-19a)
with exceptional affinity, and we showed that cationic modification is absolutely
critical for binding. Furthermore, formation of the MlRA-pre-miR-19a complex
inhibited Dicer-mediated cleavage of the pre-miR, thus blocking formation of the
mature functional microRNA. The MlRA reported here not only represents the first
l-aptamer to be evolved by using modified nucleotides but also the first modified
aptamer (of any type) to be selected against a structured RNA target. Our results
demonstrate that functionalized l-aptamers, which are intrinsically nuclease
resistant, provide an attractive approach for developing robust RNA-binding
reagents.
PMID- 28696510
TI - Expanding the Baveno VI criteria for the screening of varices in patients with
compensated advanced chronic liver disease.
AB - : Patients with compensated advanced chronic liver disease (cACLD) can safely
avoid screening endoscopy with a platelet count >150 * 109 cells/L and a liver
stiffness measurement (LSM) <20 kPa (Baveno VI criteria). However, the total
number of avoided endoscopies using this rule is relatively low. We aimed at
expanding the Baveno VI criteria and validating them in additional cohorts.
Patients from the Anticipate cohort (499 patients with cACLD of different
etiologies) were used to study the performance of different thresholds of
platelets and LSM for the identification of patients at very low risk (<5%) of
having varices needing treatment (VNT). The new criteria (Expanded-Baveno VI)
were validated in two additional cohorts from London (309 patients) and Barcelona
(117 patients). The performance of the new criteria by etiology of cACLD was also
assessed. The best new expanded classification rule was platelet count >110 * 109
cells/L and LSM <25 kPa. This was validated in the two additional cohorts.
Overall, the Expanded-Baveno VI criteria would potentially spare 367 (40%)
endoscopies (21% with Baveno VI criteria) with a risk of missing VNT of 1.6% (95%
confidence interval, 0.7%-3.5%) in patients within the criteria and 0.6% (95%
confidence interval, 0.3%-1.4%) in the overall population of 925 patients
evaluated. The Expanded-Baveno VI criteria performed well in patients with cACLD
with hepatitis C virus and alcoholic and nonalcoholic steatohepatitis.
CONCLUSION: The new Expanded-Baveno VI criteria spare more endoscopies than the
original criteria with a minimal risk of missing VNT in most of the main
etiologies of cACLD. (Hepatology 2017;66:1980-1988).
PMID- 28696511
TI - Direct Application of Rep-PCR on Type I Sourdough Matrix to Monitor the Dominance
and Persistence of a Lactobacillus plantarum Starter Throughout Back-Slopping.
AB - This study describes the optimization and application of repetitive element-PCR
(rep-PCR) technique directly on microbial DNA extracted from type I sourdoughs
for fast monitoring of a Lb. plantarum starter strain (P1FMC) throughout daily
back-slopping. The challenge was to follow and study the performance of a starter
culture directly in sourdoughs without cultivation on selective media. The
extraction of good quality microbial DNA suitable for amplification from a
complex matrix such as dough was the first target. In addition, the objective to
obtain a clear rep-PCR profile referable to a specific starter strain among a
microbial community was pursued. Co-inoculum trials, in flour matrix, with Lb.
plantarum P1FMC and L. lactis LC71 strains and, subsequently, type I sourdough
back-slopping trials were performed. The rep-PCR amplification profiles obtained
were clearly referable to that of Lb. plantarum P1FMC starter in both co-inoculum
trials (also when it was present with one order of magnitude less with respect to
L. lactis LC71) and back-slopping trials where it dominated the fermentation
process with loads of 108 cfu g-1 and prevailed on the autochthonous microbiota.
Thus, the approach proposed in this paper could be considered a methodological
advancement, based on a culture-independent one-step rep-PCR, suitable for fast
monitoring of starter performance.
PMID- 28696512
TI - Involvement of insulin resistance in normoglycaemic obese patients with
periodontitis: A cross-sectional study.
AB - AIM: We explored the association between obesity and periodontitis with the aim
of determining the possible role of insulin resistance (IR) in this relationship.
MATERIALS AND METHODS: A total of 212 subjects-110 obese and 102 lean individuals
were evaluated for periodontal disease and divided according to IR: a lean group
without IR (LWIR), an obese group without IR (OWIR), and an obese group with IR
(OIR). Anthropometric, metabolic, inflammatory and periodontal parameters were
evaluated. RESULTS: Periodontitis was more prevalent in obese (80.9%) than in
lean subjects (41.2%), with the former group showing a risk of periodontitis
sixfold that of the latter. Obese subjects as a whole displayed higher diastolic
blood pressure, TNFalpha and hsCRP and lower HDL cholesterol than lean subjects.
OIR had higher systolic blood pressure, glucose, insulin, HOMA-IR, A1c,
triglycerides and number of teeth with PD >= 4 mm than OWIR, while other
periodontal variables remained unaltered. The multivariable regression model
showed that probing depth, bleeding on probing and HOMA-IR were independent
predictors of number of teeth with PD >= 4 mm. CONCLUSION: Our data support an
association between obesity and periodontitis, and point to a central role of IR.
Periodontitis tends to be more extensive in obese patients with IR.
PMID- 28696513
TI - RuP2 -Based Catalysts with Platinum-like Activity and Higher Durability for the
Hydrogen Evolution Reaction at All pH Values.
AB - Highly active, stable, and cheap Pt-free catalysts for the hydrogen evolution
reaction (HER) are under increasing demand for future energy conversion systems.
However, developing HER electrocatalysts with Pt-like activity that can function
at all pH values still remains as a great challenge. Herein, based on our
theoretical predictions, we design and synthesize a novel N,P dual-doped carbon
encapsulated ruthenium diphosphide (RuP2 @NPC) nanoparticle electrocatalyst for
HER. Electrochemical tests reveal that, compared with the Pt/C catalyst, RuP2
@NPC not only has Pt-like HER activity with small overpotentials at 10 mA cm-2
(38 mV in 0.5 m H2 SO4 , 57 mV in 1.0 m PBS and 52 mV in 1.0 m KOH), but
demonstrates superior stability at all pH values, as well as 100 % Faradaic
yields. Therefore, this work adds to the growing family of transition-metal
phosphides/heteroatom-doped carbon heterostructures with advanced performance in
HER.
PMID- 28696514
TI - Modulation of lateral positions of Bragg peaks via magnetic fields inside cancer
patients: Toward magnetic field modulated proton therapy.
AB - PURPOSE: This work investigated whether the Bragg peak (BP) positions of proton
beams can be modulated to produce uniform doses and cover a tumor under the
magnetic fields inside cancer patients, and whether magnetic field modulated
proton therapy (MMPT) is effective in vital organ protection. METHODS: The
authors initially constructed an ideal water phantom comprising a central tumor
surrounded by cuboid organ regions using GEANT4. Second, we designed the proton
beams passing through the gap between two adjacent organ regions during beam
configuration. Third, we simulated the beam transports under magnetic fields
inside the phantom through GEANT4. Then, the beams were discarded, which did not
stop in the tumor. Fourth, the authors modulated the intensities of the remaining
beams to produce uniform tumor doses. Subsequently, the calculated MMPT doses
were compared with those of traditional methods, such as single, opposing,
orthogonal, and box fields. Moreover, the authors repeated the above research
procedures for abdominal anatomies comprising tumors at the pancreatic tail and
liver to evaluate whether MMPT is effective for the human anatomy. RESULTS: For
the water phantom, the vital organ doses were approximately 50%, 30%, 30%, and
15% for the single, opposing, orthogonal, and box fields, respectively. As the
vital organ doses decreased, the organ volume receiving proton irradiations for
the opposing, orthogonal, and box fields increased by two, two, and four times
compared with that for the single field. The vital organ volume receiving proton
irradiations were controlled to a fairly low level through MMPT, whereas the BP
positions of the proton beams were properly modulated through the magnetic fields
inside the phantom. The tumor was sufficiently covered by a 95% dose line, and
the maximum tumor doses were smaller than 110%. For the pancreatic tumor case,
the proton beams were curved and bypassed the kidney to generate uniform doses
inside the tumor through MMPT. In the liver tumor case, the liver volume
receiving proton irradiations was reduced by approximately 40% through MMPT
compared with traditional methods. CONCLUSIONS: The BP positions can be
intentionally modulated to produce uniform tumor doses under the magnetic fields
inside cancer patients. In some special cases, the vital organs surrounding the
tumor can almost be exempted from proton irradiations without sacrificing tumor
dose coverage through MMPT. For the tumors inside parallel organs, the parallel
organ volume receiving proton irradiations was largely reduced through MMPT. The
results of this study can serve as beneficial implications for future proton
therapy studies with reduced vital organ damage and complications.
PMID- 28696515
TI - tBHQ Suppresses Osteoclastic Resorption in Xenogeneic-Treated Dentin Matrix-Based
Scaffolds.
AB - Extracellularmatrix (ECM)-based scaffolds are important for their potential
therapeutic application. Treated dentin matrix (TDM), a kind of ECM, seeded with
allogeneic dental follicle stem cells (TDM/aDFC) provides a suitable inductive
microenvironment for tooth root regeneration. Considering the limited sources,
xenogeneic TDM (xTDM) is a possible alternative to allogeneic TDM; however, xTDM
based scaffold presents severe osteolysis and resorption lacunae causing
regenerated tooth root failure. Immune response-induced excessive
osteoclastogenesis plays a critical role in xenogeneic scaffold osteolysis and
resorption. The impact of antioxidant, tert-butylhydroquinone (tBHQ), on
xTDM/aDFCs-induced osteoclastogenesis and osteoclastic resorption in vivo and in
vitro are investigated. tBHQ upregulates heme oxygenase-1 release and
downregulates high mobility group box 1 mRNA expression. mRNA expression of other
osteoclast-related genes including nuclear factor-kappa Bp65, receptor activator
of nuclear factor kappa-B, nuclear factor of activated T-cells cytoplasmic 1,
cathepsin K, and integrin beta3, also decreases significantly. Furthermore, tBHQ
treated xTDM/aDFCs scaffolds implanted into rhesus macaques show reduced
osteolysis and osteoclastic resorption by microcomputed tomography and tartrate
resistant acid phosphatase staining. tBHQ-induced suppression of xTDM/aDFC
induced osteoclastogenesis and osteoclastic resorption presents a new strategy
for the regeneration of biological tooth root and could be applied to the
regeneration of other complex tissues and organs.
PMID- 28696516
TI - Knowing Requires Data.
PMID- 28696517
TI - Warm season precipitation signal in delta2 H values of wood lignin methoxyl
groups from high elevation larch trees in Switzerland.
AB - RATIONALE: In this study, we tested stable hydrogen isotope ratios of wood lignin
methoxyl groups (delta2 Hmethoxyl values) as a palaeoclimate proxy in
dendrochronology. This is a quite new method in the field of dendrochronology and
the sample preparation is much simpler than the methods used before to measure
delta2 H values from wood. METHODS: We measured delta2 Hmethoxyl values in high
elevation larch trees (Larix decidua Mill.) from Simplon Valley (southern
Switzerland). Thirty-seven larch trees were sampled and five individuals analysed
for their delta2 Hmethoxyl values at annual (1971-2009) and pentadal resolution
(1746-2009). The delta2 Hmethoxyl values were measured as CH3 I released upon
treatment of the dried wood samples with hydroiodic acid. 10-90 MUL from the head
space were injected into the gas chromatography/high-temperature
conversion/isotope ratio mass spectrometry (GC/HTC-IRMS) system. RESULTS: Testing
the climate response of the delta2 Hmethoxyl values, the annually resolved series
show a positive correlation of r = 0.60 with June/July precipitation. The
pentadally resolved delta2 Hmethoxyl series do not show any significant
correlation to climate parameters. CONCLUSIONS: Increased precipitation during
June and July, which are on average warm and relatively dry months, results in
higher delta2 H values of the xylem water and, therefore, higher delta2 H values
in the lignin methoxyl groups. Therefore, we suggest that delta2 Hmethoxyl values
of high elevation larch trees might serve as a summer precipitation proxy.
PMID- 28696518
TI - Statistical Profiling of One Promiscuous Protein Binding Site: Illustrated by
Urokinase Catalytic Domain.
AB - While recent literature focuses on drug promiscuity, the characterization of
promiscuous binding sites (ability to bind several ligands) remains to be
explored. Here, we present a proteochemometric modeling approach to analyze
diverse ligands and corresponding multiple binding sub-pockets associated with
one promiscuous binding site to characterize protein-ligand recognition. We
analyze both geometrical and physicochemical profile correspondences. This
approach was applied to examine the well-studied druggable urokinase catalytic
domain inhibitor binding site, which results in a large number of complex
structures bound to various ligands. This approach emphasizes the importance of
jointly characterizing pocket and ligand spaces to explore the impact of ligand
diversity on sub-pocket properties and to establish their main profile
correspondences. This work supports an interest in mining available 3D holo
structures associated with a promiscuous binding site to explore its main protein
ligand recognition tendency.
PMID- 28696519
TI - Preferences for groundnut products among urban residents in Ghana.
AB - BACKGROUND: The present study identifies factors influencing preferences for
common groundnut products using information about product perceptions from
residents in Ghana's cities collected in 2011. In Ghana, domestically produced
groundnuts, processed into a variety of groundnut products, are a vital source of
protein and other nutrients. RESULTS: Response summaries provide insights about
the eating frequency of various products, whereas a bivariate ordered probit
model identifies factors influencing preferences for groundnut paste and roasted
groundnuts. Attributes such as taste, protein content and healthfulness are
important for roasted groundnuts, whereas aroma, taste and protein content are
associated with a preference for groundnut paste. Large households prefer paste,
whereas the less educated and those from households with children prefer roasted
groundnuts. Adding a child (4-12 years old) increases probability of 'liking very
much' roasted groundnuts and an additional adult at home changes that probability
regarding groundnut paste. College-educated consumers prefer groundnut paste less
than those with less education. Consumers from Tamale and Takoradi prefer roasted
groundnuts and groundnut paste more than Accra households. CONCLUSIONS: Taste and
protein content are attributes of groundnut paste and roasted groundnuts
preferred by consumers. Location is a significant factor shaping preference for
roasted groundnuts and groundnut paste. (c) 2017 Society of Chemical Industry.
PMID- 28696520
TI - Delays in presentation and diagnosis of pulmonary tuberculosis: a retrospective
study of a tertiary health service in Western Melbourne, 2011-2014.
AB - BACKGROUND: Effective tuberculosis (TB) control relies on early diagnosis and
prompt treatment commencement. AIM: To investigate delays in presentation and
diagnosis of pulmonary TB (PTB) in a low incidence setting in Western Melbourne.
METHODS: A single-centred retrospective observational cohort study of symptomatic
patients >= 18 years newly diagnosed with PTB that were commenced on treatment
between 1 December 2011 and 1 December 2014 at a tertiary teaching hospital in
Western Melbourne. Main outcome measures included median duration of patient,
health system and total delays to diagnosis of PTB and clinical factors
associated with prolonged patient (>35 days) and health system (>21 days) delay.
RESULTS: A total of 133 patients were included. The median (range) duration of
patient, health system and total delay to diagnosis were 28 (0-610), 18 (0-357)
and 89 (1-730) days respectively. Prolonged patient delay was associated with
being from a country with an annual TB incidence of <50/100 000 (odds ratio (OR)
5.98, 95% confidence interval (CI) 1.19, 29.98) and diabetes mellitus (OR 3.02,
95% CI 1.04, 8.78) in multivariate analysis. Being Australian-born or a resident
of Australia >=6 years (OR 0.03, 95% CI 0.12, 0.74; OR 0.30, 95% CI 0.00, 0.033
respectively) was associated with reduced patient delay. CONCLUSIONS: In this low
incidence, high-resource setting, patient delays contribute most to total delay
in PTB diagnosis. Strategies addressing this aspect of the TB diagnosis pathway,
such as health literacy and promotion programmes for new migrants and raised
primary healthcare awareness, could have the largest impact on reducing total PTB
diagnosis delays.
PMID- 28696521
TI - Characterization of the Rabbit as an In Vitro and In Vivo Model to Assess the
Effects of Fibrinogenolytic Activity of Snake Venom on Coagulation.
AB - Several in vitro investigations have demonstrated that anticoagulant effects of
fibrinogenolytic snake venom metalloproteinases have been abrogated in human
plasma by modifying fibrinogen with iron (Fe) and carbon monoxide (CO) to prevent
catalysis or by directly inhibiting these enzymes with CO. To translate these
findings, we chose to assess the rabbit as a model of envenomation with Crotalus
atrox venom. It was determined with thrombelastography that 15 times the
concentration of venom noted to compromise coagulation in plasma in vitro was
required to cause coagulopathy in vivo, likely secondary to venom binding to
blood cells and being cleared from the circulation rapidly. Unlike human plasma,
rabbit plasma pre-treated with Fe/CO was not protected from fibrinogenolysis by
venom. Consequently, the administration of purified human fibrinogen (with or
without Fe/CO) would be required before venom administration to rabbits. Of
greater interest, venom exposed to CO had complete loss of fibrinogenolytic
effect in rabbit plasma and partial loss of activity in whole blood, indicative
of unbinding of CO from venom and binding to haemoglobin. Thus, venom exposed to
CO could remain partially or completely inhibited in whole blood long enough for
clearance from the circulation, allowing rabbits to be a useful model to test the
efficacy of regional CO administration to the bite site. Future investigations
are planned to test these novel approaches to attenuate venom-mediated
coagulopathy in the rabbit.
PMID- 28696522
TI - Assessment of the inferior mesenteric vein diameter as a surrogate marker to
evaluate response to neoadjuvant chemoradiotherapy for locally advanced rectal
adenocarcinoma.
AB - AIM: Neoadjuvant chemoradiotherapy for locally advanced rectal cancer aims to
downstage prior to definitive management. Repeat imaging assessment of the tumour
post-therapy has implications for treatment. Our aim was to assess if the
inferior mesenteric vein (IMV) diameter measured on CT can be used as a surrogate
marker for evaluation of tumour response to neoadjuvant treatment. METHOD: IMV
diameter was assessed in patients with and without locally advanced rectal
cancer, pre- and post-radiotherapy, to ascertain if IMV diameter is a surrogate
marker of tumour response. RESULTS: IMV diameter was 5.9 mm in patients with
rectal cancer vs 4.7 mm in patients without (P = 0.0001). The baseline IMV
diameter was significantly higher for cases with local lymphadenopathy [N0 5.2 mm
vs N1/2 6 mm (P = 0.0059)] and extramural venous invasion (EMVI) [negative 5.4 mm
vs positive 6.4 mm (P = 0.0001)]. Post-radiotherapy there was a significant
decrease in the IMV diameter in cases with treatment response compared to non
responders: the percentage change in IMV diameter was a 17.54% decrease vs 1.39%
increase (P = 0.0001). These results were reproduced on comparing between
magnetic resonance tumour regression grades using ANOVA (P = 0.0001). There was
also a significant decrease in IMV diameter when assessing lymph node (LN) and
EMVI response vs non-responders (P = 0.0001 and 0.0001 respectively). CONCLUSION:
Patients with rectal cancer have a dilated IMV compared with patients without
rectal cancer. We confirm that IMV diameter is a potential surrogate marker of LN
status and EMVI at baseline. IMV diameter is also a marker of tumour, LN and EMVI
response to chemoradiotherapy.
PMID- 28696523
TI - Nematic DNA Thermotropic Liquid Crystals with Photoresponsive Mechanical
Properties.
AB - Over the last decades, water-based lyotropic liquid crystals of nucleic acids
have been extensively investigated because of their important role in biology.
Alongside, solvent-free thermotropic liquid crystals (TLCs) from DNA are gaining
great interest, owing to their relevance to DNA-inspired optoelectronic
applications. Up to now, however, only the smectic phase of DNA TLCs has been
reported. The development of new mesophases including nematic, hexagonal, and
cubic structures for DNA TLCs remains a significant challenge, which thus limits
their technological applications considerably. In this work, a new type of DNA
TLC that is formed by electrostatic complexation of anionic oligonucleotides and
cationic surfactants containing an azobenzene (AZO) moiety is demonstrated. DNA
AZO complexes form a stable nematic mesophase over a temperature range from -7 to
110 degrees C and retain double-stranded DNA structure at ambient temperature.
Photoisomerization of the AZO moieties from the E- to the Z-form alters the
stiffness of the DNA-AZO hybrid materials opening a pathway toward the
development of DNA TLCs as stimuli-responsive biomaterials.
PMID- 28696524
TI - Molecular Hyperthermia: Spatiotemporal Protein Unfolding and Inactivation by
Nanosecond Plasmonic Heating.
AB - Spatiotemporal control of protein structure and activity in biological systems
has important and broad implications in biomedical sciences as evidenced by
recent advances in optogenetic approaches. Here, this study demonstrates that
nanosecond pulsed laser heating of gold nanoparticles (GNP) leads to an ultrahigh
and ultrashort temperature increase, coined as "molecular hyperthermia", which
causes selective unfolding and inactivation of proteins adjacent to the GNP.
Protein inactivation is highly dependent on both laser pulse energy and GNP size,
and has a well-defined impact zone in the nanometer scale. It is anticipated that
the fine control over protein structure and function enabled by this discovery
will be highly enabling within a number of arenas, from probing the biophysics of
protein folding/unfolding to the nanoscopic manipulation of biological systems
via an optical trigger, to developing novel therapeutics for disease treatment
without genetic modification.
PMID- 28696525
TI - CuAAC in a Distal Pocket: Metal Active-Template Synthesis of Strapped-Porphyrin
[2]Rotaxanes.
AB - The synthesis of a porphyrin rotaxane by dipolar cycloaddition takes advantage of
the ditopic character of a phenanthroline-strapped porphyrin. The success of the
click reaction was conditioned by the presence of both a coordinatively
unsaturated metal in the porphyrin and a copper(I) bound to the phenanthroline,
pointing at a new "tandem active metal template" mechanism.
PMID- 28696526
TI - Highlights from the 2016 North American Cystic Fibrosis Conference.
AB - The 30th annual North American Cystic Fibrosis Conference (NACFC) was held in
Orlando, FL, on October 27-29, 2016. Abstracts were published in a supplement to
Pediatric Pulmonology. This review summarizes several major topic areas addressed
at the conference: the pathophysiology of cystic fibrosis (CF) lung disease,
clinical trials, clinical management issues, and quality improvement. We sought
to provide an overview of emerging concepts in several areas of CF research and
care, rather than a comprehensive review of the conference. Citations from the
conference are by first author and abstract number or symposium number, as
designated in the supplement.
PMID- 28696527
TI - Extracellular matrix stiffness affects contractility in adult rat cardiomyocytes:
implications for dynamic nitric oxide signalling and calcium handling.
PMID- 28696528
TI - Endogenous sequence patterns predispose the repair modes of CRISPR/Cas9-induced
DNA double-stranded breaks in Arabidopsis thaliana.
AB - The possibility to predict the outcome of targeted DNA double-stranded break
(DSB) repair would be desirable for genome editing. Furthermore the consequences
of mis-repair of potentially cell-lethal DSBs and the underlying pathways are not
yet fully understood. Here we study the clustered regularly interspaced short
palindromic repeats (CRISPR)/Cas9-induced mutation spectra at three selected
endogenous loci in Arabidopsis thaliana by deep sequencing of long amplicon
libraries. Notably, we found sequence-dependent genomic features that affected
the DNA repair outcome. Deletions of 1-bp to <1000-bp size and/or very short
insertions, deletions >1 kbp (all due to NHEJ) and deletions combined with
insertions between 5-bp to >100 bp [caused by a synthesis-dependent strand
annealing (SDSA)-like mechanism] occurred most frequently at all three loci. The
appearance of single-stranded annealing events depends on the presence and
distance between repeats flanking the DSB. The frequency and size of insertions
is increased if a sequence with high similarity to the target site was available
in cis. Most deletions were linked to pre-existing microhomology. Deletion and/or
insertion mutations were blunt-end ligated or via de novo generated
microhomology. While most mutation types and, to some degree, their
predictability are comparable with animal systems, the broad range of deletion
mutations seems to be a peculiar feature of the plant A. thaliana.
PMID- 28696529
TI - Fast Dynamic Visualizations in Microfluidics Enabled by Fluorescent Carbon
Nanodots.
AB - Microfluidic systems have become a superior platform for explorations of
fascinating fluidic physics at microscale as well as applications in biomedical
devices, chemical reactions, drug delivery, etc. Exploitations of this platform
are built upon the fundamental techniques of flow visualizations. However, the
currently employed fluorescent materials for microfluidic visualization are far
from satisfaction, which severely hinders their widespread applications. Here
fluorescent carbon nanodots are documented as a game-changer, applicable in
versatile fluidic environment for the visualization in microfluidics with
unprecedented advantages. One of the fastest fluorescent imaging speeds up to
2500 frames per second under a normal contionous wave (CW) laser line is achieved
by adopting carbon nanodots in microfluidics. Besides better visualizations of
the fluid or interface, fluorescent carbon nanodots-based microparticles enable
quantitative studies of high speed dynamics in fluids at microscale with a more
than 90% lower cost, which is inaccessible by traditionally adopted fluorescent
dye based seeding particles. The findings hold profound influences to
microfluidic investigations and may even lead to revolutionary changes to the
relevant industries.
PMID- 28696530
TI - Immunogenicity and safety of single-dose, 13-valent pneumococcal conjugate
vaccine in pediatric and adolescent oncology patients.
AB - BACKGROUND: Children receiving immunosuppressive treatment for cancer are at high
risk for invasive pneumococcal disease. The 13-valent pneumococcal conjugate
vaccine (PCV13) can prevent pneumococcal disease in healthy children; however,
there is an absence of literature regarding the benefit of PCV13 in
immunocompromised children with cancer. METHODS: A prospective, open-label cohort
study recruited children between ages 1 and 18 years who were receiving active
immunosuppressive therapy (AIT) or were within 12 months after completing
immunosuppressive therapy (CIT). Blood samples were taken before and 4 weeks
after the administration of single-dose PCV13. Serotype-specific immunoglobulin G
antibody titers were measured, and titers >=0.35 MUg/mL were considered
protective. Solicited side effects were recorded in a 7-day diary after
vaccination. RESULTS: Eighty-five children were recruited. At baseline, <=50% had
protective antibody titers against Streptococcus pneumoniae for 10 serotypes in
the AIT group and for 8 serotypes in the CIT group. Postvaccination, >=70% had
protective antibody titers for 9 and 11 serotypes in the AIT and CIT groups,
respectively. Both groups had comparable responses to PCV7 serotypes, whereas a
significantly higher proportion in the CIT group achieved protective antibody
titers to PCV13 serotypes. There was a low rate of serious adverse events (3.5%).
CONCLUSIONS: A single-dose of PCV13 is safe and immunogenic in children diagnosed
with cancer. All children who are receiving therapy for cancer should receive a
single dose of PCV13 as soon as possible after diagnosis, regardless of prior PCV
exposure. The current data support the recommendation for an additional dose of
PCV13 after the completion of immunosuppressive therapy to provide additional
protection against invasive pneumococcal disease. Cancer 2017;123:4215-4223. (c)
2017 American Cancer Society.
PMID- 28696531
TI - Validation of post-traumatic stress disorder (PTSD) and complex PTSD using the
International Trauma Questionnaire.
AB - OBJECTIVE: The 11th version of the International Classification of Diseases (ICD
11) has proposed two related trauma diagnoses: Post-traumatic stress disorder
(PTSD) and Complex PTSD (CPTSD). Using a newly developed, disorder-specific
measure of PTSD and CPTSD called the International Trauma Questionnaire (ITQ) the
current study will (i) assess the factorial validity of ICD-11 PTSD and CPTSD;
(ii) provide the first test of the discriminant validity of these constructs; and
(iii) provide the first comparison of ICD-11, and Diagnostic and Statistical
Manual, Fifth Edition (DSM-5), PTSD diagnostic rates using disorder-specific
measures. METHOD: ICD-11 and DSM-5 PTSD-specific measures were completed by a
British clinical sample of trauma-exposed patients (N = 171). The structure and
validity of ICD-11 PTSD and CPTSD were assessed by means of factor analysis and
assessing relationships with criterion variables. RESULTS: Diagnostic rates under
ICD-11 were significantly lower than those under DSM-5. A two-factor second-order
model reflecting the distinction between PTSD and CPTSD best represented the data
from the ITQ; and the PTSD and CPTSD factors differentially predicted multiple
psychological variables. CONCLUSION: The factorial and discriminant validity of
ICD-11 PTSD and CPTSD was supported, and ICD-11 produces fewer diagnostic cases
than DSM-5.
PMID- 28696532
TI - Unmet contraceptive needs in rural communities in the Dominican Republic during
an international Zika virus outbreak.
PMID- 28696533
TI - Highly Enantioselective Catalytic Vinylogous Propargylation of Coumarins Yields a
Class of Autophagy Inhibitors.
AB - A highly enantioselective copper-catalyzed vinylogous propargylic substitution
has been developed. Aromatic and aliphatic propargylic esters react smoothly with
substituted coumarins under mild reaction conditions to give the desired products
with excellent yields and enantioselectivities. Subsequent single-step
transformations enable the synthesis of a wide range of multifunctional and
diverse compounds, and allow the efficient combination of different natural
product fragments. Investigation of the obtained compound collection in cell
based assays monitoring changes in phenotype led to the discovery of a novel
class of autophagy inhibitors.
PMID- 28696534
TI - A fusion protein of interleukin-4 and interleukin-10 protects against blood
induced cartilage damage in vitro and in vivo.
AB - : Essentials Targeted treatment for hemophilic arthropathy, still causing
significant morbidity, is lacking. This study evaluates the efficacy of a fusion
of protein of interleukin(IL)-4 and IL-10. In vitro the fusion protein prevents
blood-induced cartilage damage in a dose-dependent manner. In hemophilic mice,
the IL4-10 fusion protein ameliorates cartilage damage upon joint bleeding.
SUMMARY: Background Joint damage still causes significant morbidity in
hemophilia. It results from synovial inflammation and direct cartilage
degenerating properties of blood components. Interleukin (IL)-4 and IL-10 have
been shown to protect cartilage from blood-induced damage. Recently an IL4-10
fusion protein has been developed to combine the function of IL-4 and IL-10 and
increase their bioavailability. Objectives In this study we evaluate whether this
IL4-10 fusion protein protects against blood-induced joint damage. Methods In
vitro, human cartilage explants were exposed to whole blood and simultaneously to
a broad concentration range of the IL4-10 fusion protein. Effects on cartilage
matrix turnover were compared with the individual cytokines. Moreover, the
influence of the fusion protein and its individual components on IL-1beta and IL
6 production was investigated. In hemophilia A mice, the effect of intra
articular treatment on synovitis and cartilage damage resulting from joint
bleeding was evaluated by histochemistry. Results In vitro, the fusion protein
prevented blood-induced cartilage damage in a dose-dependent manner, with equal
effectiveness to the combination of the separate cytokines. In whole blood
cultures 10 ng mL-1 fusion protein completely blocked the production of IL-1beta
and IL-6 by monocytes/macrophages. In hemophilic mice, intra-articular injection
of IL-4 and IL-10 did not influence synovitis or cartilage degeneration. In
contrast, equimolar amounts of the fusion protein attenuated cartilage damage
upon repeated joint bleeding, although synovial inflammation was hardly affected.
Conclusions Overall, this study shows that the IL4-10 fusion protein prevents
blood-induced cartilage damage in vitro and ameliorates cartilage degeneration
upon joint bleeding in hemophilic mice.
PMID- 28696535
TI - BMI predicts exercise induced bronchoconstriction in asthmatic boys.
AB - BACKGROUND: Exercise induced bronchoconstriction (EIB) is a frustrating morbidity
of asthma in children. Obesity has been associated with asthma and with more
severe EIB in asthmatic children. OBJECTIVES: To quantify the effect of BMI on
the risk of the occurrence of EIB in children with asthma. METHODS: Data were
collected from six studies in which exercise challenge tests were performed
according to international guidelines. We included 212 Children aged 7-18 years,
with a pediatrician-diagnosed mild-to-moderate asthma. RESULTS: A total of 103 of
212 children (49%) had a positive exercise challenge (fall of FEV1 >= 13%). The
severity of EIB, as measured by the maximum fall in FEV1 , was significantly
greater in overweight and obese children compared to normal weight children
(respectively 23.9% vs 17.9%; P = 0.045). Asthmatic children with a BMI z-score
around +1 had a 2.9-fold higher risk of the prevalence of EIB compared to
children with a BMI z-score around the mean (OR 2.9; 95%CI: 1.3-6.1; P < 0.01).
An increase in BMI z-score of 0.1 in boys led to a 1.4-fold increased risk of EIB
(OR 1.4; 95%CI: 1.0-1.9; P = 0.03). A reduction in pre-exercise FEV1 was
associated with a higher risk of EIB (last quartile six times higher risk
compared to highest quartile (OR 6.1 [95%CI 2.5-14.5]). CONCLUSIONS: The severity
of EIB is significantly greater in children with overweight and obesity compared
to non-overweight asthmatic children. Furthermore, this study shows that the BMI
z-score, even with a normal weight, is strongly associated with the incidence of
EIB in asthmatic boys.
PMID- 28696536
TI - An emergency call system for patients in locked-in state using an SSVEP-based
brain switch.
AB - Patients in a locked-in state (LIS) due to severe neurological disorders such as
amyotrophic lateral sclerosis (ALS) require seamless emergency care by their
caregivers or guardians. However, it is a difficult job for the guardians to
continuously monitor the patients' state, especially when direct communication is
not possible. In the present study, we developed an emergency call system for
such patients using a steady-state visual evoked potential (SSVEP)-based brain
switch. Although there have been previous studies to implement SSVEP-based brain
switch system, they have not been applied to patients in LIS, and thus their
clinical value has not been validated. In this study, we verified whether the
SSVEP-based brain switch system can be practically used as an emergency call
system for patients in LIS. The brain switch used for our system adopted a
chromatic visual stimulus, which proved to be visually less stimulating than
conventional checkerboard-type stimuli but could generate SSVEP responses strong
enough to be used for brain-computer interface (BCI) applications. To verify the
feasibility of our emergency call system, 14 healthy participants and 3 patients
with severe ALS took part in online experiments. All three ALS patients
successfully called their guardians to their bedsides in about 6.56 seconds.
Furthermore, additional experiments with one of these patients demonstrated that
our emergency call system maintains fairly good performance even up to 4 weeks
after the first experiment without renewing initial calibration data. Our results
suggest that our SSVEP-based emergency call system might be successfully used in
practical scenarios.
PMID- 28696537
TI - Fire influences the structure of plant-bee networks.
AB - Fire represents a frequent disturbance in many ecosystems, which can affect plant
pollinator assemblages and hence the services they provide. Furthermore, fire
events could affect the architecture of plant-pollinator interaction networks,
modifying the structure and function of communities. Some pollinators, such as
wood-nesting bees, may be particularly affected by fire events due to damage to
the nesting material and its long regeneration time. However, it remains unclear
whether fire influences the structure of bee-plant interactions. Here, we used
quantitative plant-wood-nesting bee interaction networks sampled across four
different post-fire age categories (from freshly-burnt to unburnt sites) in an
arid ecosystem to test whether the abundance of wood-nesting bees, the breadth of
resource use and the plant-bee community structure change along a post-fire age
gradient. We demonstrate that freshly-burnt sites present higher abundances of
generalist than specialist wood-nesting bees and that this translates into lower
network modularity than that of sites with greater post-fire ages. Bees do not
seem to change their feeding behaviour across the post-fire age gradient despite
changes in floral resource availability. Despite the effects of fire on plant-bee
interaction network structure, these mutualistic networks seem to be able to
recover a few years after the fire event. This result suggests that these
interactions might be highly resilient to this type of disturbance.
PMID- 28696538
TI - Dimension-Controllable Microtube Arrays by Dynamic Holographic Processing as 3D
Yeast Culture Scaffolds for Asymmetrical Growth Regulation.
AB - Transparent microtubes can function as unique cell culture scaffolds, because the
tubular 3D microenvironment they provide is very similar to the narrow space of
capillaries in vivo. However, how to realize the fabrication of microtube-arrays
with variable cross-section dynamically remains challenging. Here, a dynamic
holographic processing method for producing high aspect ratio (~20) microtubes
with tunable outside diameter (6-16 um) and inside diameter (1-10 um) as yeast
culture scaffolds is reported. A ring-structure Bessel beam is modulated from a
typical Gaussian-distributed femtosecond laser beam by a spatial light modulator.
By combining the axial scanning of the focused beam and the dynamic display of
holograms, dimension-controllable microtube arrays (straight, conical, and drum
shape) are rapidly produced by two-photon polymerization. The outside and inside
diameters, tube heights, and spatial arrangements are readily tuned by loading
different computer-generated holograms and changing the processing parameters.
The transparent microtube array as a nontrivial tool for capturing and culturing
the budding yeasts reveals the significant effect of tube diameter on budding
characteristics. In particular, the conical tube with the inside diameter varying
from 5 to 10 um has remarkable asymmetrical regulation on the growth trend of
captured yeasts.
PMID- 28696539
TI - O?O bond homolysis in hydrogen peroxide.
AB - O?O bond homolysis in hydrogen peroxide (H2 O2 ) has been studied using
theoretical methods of four conceptually different types: hybrid DFT (B3LYP, M06
2X), double-hybrid DFT (B2-PLYP), coupled-cluster (CCSD(T)), and
multiconfigurational (CASPT2). In addition, the effects of basis set size have
also been analyzed. For all of these methods, the O?O bond homolysis in hydrogen
peroxide has been found to proceed through hydrogen bonded radical pair
complexes. Reaction barriers for collapse of the radical pairs to hydrogen
peroxide are minute, leading to an overall very flat potential energy surface.
However, hydrogen bonding energies in the radical pair complex expressed as the
energy difference to two separate hydroxyl radicals are sizeable and exceed 10
kJ/mol for all theoretical methods considered in this study. (c) 2017 Wiley
Periodicals, Inc.
PMID- 28696540
TI - Conserved hydrophobic residues in the CARP/beta-sheet domain of cyclase
associated protein are involved in actin monomer regulation.
AB - Cyclase-associated protein (CAP) is a multidomain protein that promotes actin
filament dynamics. The C-terminal region of CAP contains a CAP and X-linked
retinitis pigmentosa 2 protein (CARP) domain (or a beta-sheet domain), which
binds to actin monomer and is essential for enhancing exchange of actin-bound
nucleotides. However, how the CARP domain binds to actin is not clearly
understood. Here, we report that conserved hydrophobic residues in the CARP
domain play important roles in the function of CAP to regulate actin dynamics.
Single mutations of three conserved surface-exposed hydrophobic residues in the
CARP domain of CAS-2, a Caenorhabditis elegans CAP, significantly reduce its
binding to actin monomers and suppress its nucleotide exchange activity on actin.
As a result, these mutants are weaker than wild-type to compete with ADF/cofilin
to promote recycling of actin monomers for polymerization. A double mutation
(V367A/I373A) eliminates these actin-regulatory functions of CAS-2. These
hydrophobic residues and previously identified functional residues are scattered
on a concave beta-sheet of the CARP domain, suggesting that a wide area of the
beta-sheet is involved in binding to actin. These observations suggest that the
CARP domain of CAP binds to actin in a distinct manner from other known actin
binding proteins.
PMID- 28696541
TI - Mechanistic investigation inspired "on water" reaction for hydrobromic acid
catalyzed Friedel-Crafts-type reaction of beta-naphthol and formaldehyde.
AB - The mechanism of the HBr-catalyzed Friedel-Crafts-type reaction between beta
naphthol and HCHO was investigated by DFT to improve this reaction. The HBr-H2 O
co-catalyzed the preferential pathway undergoes the concerted nucleophilic
addition and hydrogen shift, stepwise followed by H2 O elimination and the C?C
bond formation. The origin of the high catalytic activity of HBr is ascribed to
C?H...Br- and O?H...Br- interactions, which suggest that the active species is Br
. Moreover, water molecules efficiently assist in improving the activity of Br-
. The computational results show that solvent polarity profoundly affects the
activation barriers. To our delight, the activation barrier of the rate
determining step for the favored pathway in water is comparable (0.6 kcal/mol
difference) with that in acetonitrile. The experimental observation further
confirmed our results and demonstrated that the title reaction can be
successfully achieved "on water." Therefore, we open a new efficient and green
strategy for the synthesis of biphenol derivatives. (c) 2017 Wiley Periodicals,
Inc.
PMID- 28696542
TI - (Pro)renin receptor activation increases profibrotic markers and fibroblast-like
phenotype through MAPK-dependent ROS formation in mouse renal collecting duct
cells.
AB - Recent studies suggested that activation of the PRR upregulates profibrotic
markers through reactive oxygen species (ROS) formation; however, the exact
mechanisms have not been investigated in CD cells. We hypothesized that
activation of the PRR increases the expression of profibrotic markers through
MAPK-dependent ROS formation in CD cells. Mouse renal CD cell line (M-1) was
treated with recombinant prorenin plus ROS or MAPK inhibitors and PRR-shRNA to
evaluate their effect on the expression of profibrotic markers. PRR
immunostaining revealed plasma membrane and intracellular localization.
Recombinant prorenin increases ROS formation (6.0 +/- 0.5 vs 3.9 +/- 0.1 nmol/L
DCF/MUg total protein, P < .05) and expression of profibrotic markers CTGF (149
+/- 12%, P < .05), alpha-SMA (160 +/- 20%, P < .05), and PAI-I (153 +/- 13%, P <
.05) at 10-8 mol/L. Recombinant prorenin-induced phospho ERK 1/2 (p44 and p42)
at 10-8 and 10-6 mol/L after 20 minutes. Prorenin-dependent ROS formation and
augmentation of profibrotic factors were blunted by ROS scavengers (trolox, p
coumaric acid, ascorbic acid), the MEK inhibitor PD98059 and PRR transfections
with PRR-shRNA. No effects were observed in the presence of antioxidants alone.
Prorenin-induced upregulation of collagen I and fibronectin was blunted by ROS
scavenging or MEK inhibition independently. PRR-shRNA partially prevented this
induction. After 24 hours prorenin treatment M-1 cells undergo to epithelial
mesenchymal transition phenotype, however MEK inhibitor PD98059 and PRR knockdown
prevented this effect. These results suggest that PRR might have a significant
role in tubular damage during conditions of high prorenin-renin secretion in the
CD.
PMID- 28696543
TI - Sense of Threat as a Mediator of Peritraumatic Stress Symptom Development During
Wartime: An Experience Sampling Study.
AB - Exposure and sense of threat have been associated with stress symptoms, yet these
relationships have not been clarified during the peritraumatic period. We
investigated the mediating role of sense of threat in the link between exposure
to rocket warning sirens and stress symptoms during wartime, and the effect of
severe mental illness (SMI) status and gender on this mediation. A 30-day twice
daily smartphone-based intensive assessment of exposure to sirens, sense of
threat, and peritraumatic stress symptoms was performed during the 2014 Israel
Gaza conflict. Participants included 182 highly exposed individuals with or
without SMI. Multilevel structural equation modeling analysis was performed, with
SMI status and gender as confounders. Exposure affected the level of
peritraumatic stress symptoms both directly, b = 1.07, p < .001, 95% CI [0.32,
1.82], and indirectly, b = 0.78, p < .001, 95% CI [0.24, 1.33], through sense of
threat. The effect of sense of threat on stress symptoms was larger in the SMI
group, b = 0.86, p < .001, 95% CI [0.31, 1.40]. Gender did not have a significant
effect. Sense of threat has a key role in symptom development during the
peritraumatic timeframe. Intervention and prevention efforts should start early
and focus on promoting a sense of safety, particularly with people with SMI.
PMID- 28696544
TI - Rheology and microstructure of gels based on wheat arabinoxylans enzymatically
modified in arabinose to xylose ratio.
AB - BACKGROUND: Arabinoxylans (AX) are polysaccharides consisting of a backbone of
xyloses with arabinose substituents ester-linked to ferulic acid (FA). The
arabinose to xylose ratio (A/X) in AX may vary from 0.3 to 1.1. AX form covalent
gels by cross-linking of FA but physical interactions between AX chains also
contribute to the network formation. The present study aimed to investigate the
rheological and microstructural characteristics of gels based on AX enzymatically
modified in A/X. RESULTS: Tailored AX presented A/X ranging from 0.68 to 0.51 and
formed covalent gels. Dimers of FA content and elasticity (G') increased from
0.31 to 0.39 g kg-1 AX and from 106 to 164 Pa when the A/X in the polysaccharide
decreased from 0.68 to 0.51. Atomic force microscopy images of AX gels showed a
sponge-like microstructure at A/X = 0.68, whereas, at lower values, gels
presented a more compact microstructure. Scanning electron microscopy analysis of
AX gels show an arrangement of different morphology, passing from an imperfect
honeycomb (A/X = 0.68) to a flake-like microstructure (A/X = 0.51). CONCLUSION:
Lower A/X values favor the aggregation of AX chains resulting in an increase in
di-FA content, which improves the rheological and microstructural characteristics
of the gel formed. (c) 2017 Society of Chemical Industry.
PMID- 28696545
TI - Determination of uranium isotope ratios using a liquid sampling atmospheric
pressure glow discharge/Orbitrap mass spectrometer system.
AB - RATIONALE: The field of highly accurate and precise isotope ratio analysis, for
use in nonproliferation, has been dominated by thermal ionization and inductively
coupled plasma mass spectrometry. While these techniques are considered the gold
standard for isotope ratio analysis, a downsized instrument capable of accurately
and precisely measuring uranium (U) isotope ratios is desirable for field studies
or in laboratories with limited infrastructure. METHODS: The developed system
interfaces the liquid sampling, an atmospheric pressure glow discharge (LS-APGD)
ion source, with a high-resolution Exactive Orbitrap mass spectrometer. With this
experimental setup certified U isotope standards and unknown samples were
analyzed. The accuracy and precision of the system were then determined. RESULTS:
The LS-APGD/Exactive instrument measured a certified reference material of
natural U (235 U/238 U = 0.007261) with a 235 U/238 U ratio of 0.007065 and a %
relative standard uncertainty of 0.082, meeting the International Target Values
for the destructive analysis of U. In addition, when three unknowns were measured
and these measurements were compared with the results from an ICP multi-collector
instrument, there were no statistical differences between the two instruments.
CONCLUSIONS: The LS-APGD/Orbitrap system, while still in the preliminary stages
of development, offers highly accurate and precise isotope ratio results that
suggest a potential paradigm shift in the world of isotope ratio analysis.
Furthermore, the portability of the LS-APGD as an elemental ion source, combined
with the small size and smaller operating demands of the Orbitrap, suggests that
the instrumentation is capable of being field-deployable.
PMID- 28696546
TI - Effect of Germination and Extrusion on Physicochemical Properties and Nutritional
Qualities of Extrudates and Tortilla from Wheat.
AB - Wheat is the most common grain in the temperate region. Modifying its constituent
through food processing improves its functionality and nutrient access. In this
study, the combined effect of germination and extrusion on physicochemical
properties and nutritional qualities of extrudates and tortilla from wheat was
evaluated. Results showed that germination significantly increased (P <0.05) the
gamma-aminobutyric acid content in germinated whole wheat (GW) and extruded
germinated whole wheat (EGW) as compared to the control of whole wheat (WW).
Germination also significantly increased the protein content, reducing sugar and
total soluble sugar content in GW, while extrusion had much increasing impact on
reducing sugar content in extruded samples. Specific mechanical energy during
extrusion was reduced as feed moisture content increased from 20 to 30%. Higher
extruder screw speed (350 rpm) led to better expansion ratio at low moisture
content (20%) as compared to low screw speed (200 rpm). Extrusion significantly
increased the starch digestibility but decreased the protein digestibility in
extrudates. Tortilla made from 100% WW had about the same physical
characteristics, namely color and rollability, with tortilla made from 85% WW
with 15% GW, 85% WW with 15% extruded whole wheat (EW), and 85% WW with 15% EGW.
Tortilla made from 85% WW with 15% GW showed the largest diameter, thinnest
thickness and least extensibility. A 15% extruded germinated wheat (350 rpm)
addition in 85% WW showed significant increase of gamma-aminobutyric acid content
in tortilla compared to the control (100% WW).
PMID- 28696547
TI - Heat stress in pregnant sows: Thermal responses and subsequent performance of
sows and their offspring.
AB - Seasonal infertility is a significant problem in the swine industry, and may be
influenced by photoperiod and heat stress. Heat stress during gestation in
particular affects pregnancy, resulting in long-term developmental damage to the
offspring. This review summarizes what is known about how heat stress on the
pregnant sow affects lactation and her offspring. Sows responded to heat stress
during gestation with increased rectal temperature, respiration rate, and skin
temperature, and tended to reduce their activity-which may have changed their
body composition, increasing the adipose-to-muscle ratio. Heat stress during
gestation caused temporary insulin resistance during lactation, but this
metabolic state did not seem to affect health, lactation, or rebreeding
performance of the sow. Heat-stressed sows also presented with a shorter
gestation period and reduced litter birth weight, although weaning weights are
not affected when these sows are moved to thermoneutral conditions for lactation.
The offspring of gestational heat-stressed sows, however, possessed unique
phenotypes, including elevated body temperature, greater fat deposition, and
impaired gonad development. Thus, gestational heat stress may significantly
impact a herd through its effects on sows and their offspring. Further work is
necessary to determine the magnitude of the effects across fa cilities and
breeds.
PMID- 28696549
TI - A Concise Enantioselective Total Synthesis of (-)-Virosaine A.
AB - The total synthesis of (-)-virosaine A (1) was achieved in ten steps starting
from furan and 2-bromoacrolein. A one-pot Diels-Alder cycloaddition/organolithium
addition initiated an efficient sequence to access a key oxime/epoxide
intermediate. Heating this intermediate in acetic acid resulted in an
intramolecular epoxide opening/nitrone [3+2] cycloaddition cascade to construct
the caged core of 1 in a single step. Several methods of C-H functionalization
were assessed on the cascade product, and ultimately, a directed
lithiation/bromination effected selective C14 functionalization, enabling the
synthesis of 1.
PMID- 28696548
TI - Brain microvascular injury and white matter disease provoked by diabetes
associated hyperamylinemia.
AB - OBJECTIVE: The brain blood vessels of patients with type 2 diabetes and dementia
have deposition of amylin, an amyloidogenic hormone cosecreted with insulin. It
is not known whether vascular amylin deposition is a consequence or a trigger of
vascular injury. We tested the hypothesis that the vascular amylin deposits cause
endothelial dysfunction and microvascular injury and are modulated by amylin
transport in the brain via plasma apolipoproteins. METHODS: Rats overexpressing
amyloidogenic (human) amylin in the pancreas (HIP rats) and amylin knockout (AKO)
rats intravenously infused with aggregated amylin were used for in vivo
phenotyping. We also carried out biochemical analyses of human brain tissues and
studied the effects of the aggregated amylin on endothelial cells ex vivo.
RESULTS: Amylin deposition in brain blood vessels is associated with vessel wall
disruption and abnormal surrounding neuropil in patients with type 2 diabetes and
dementia, in HIP rats, and in AKO rats infused with aggregated amylin. HIP rats
have brain microhemorrhages, white matter injury, and neurologic deficits.
Vascular amylin deposition provokes loss of endothelial cell coverage and tight
junctions. Intravenous infusion in AKO rats of human amylin, or combined human
amylin and apolipoprotein E4, showed that amylin binds to plasma apolipoproteins.
The intravenous infusion of apolipoprotein E4 exacerbated the brain accumulation
of aggregated amylin and vascular pathology in HIP rats. INTERPRETATION: These
data identify vascular amylin deposition as a trigger of brain endothelial
dysfunction that is modulated by plasma apolipoproteins and represents a
potential therapeutic target in diabetes-associated dementia and stroke. Ann
Neurol 2017;82:208-222.
PMID- 28696550
TI - Two novel variants of the ABCG5 gene cause xanthelasmas and
macrothrombocytopenia: a brief review of hematologic abnormalities of
sitosterolemia.
AB - : Essentials Diagnosis of sitosterolemia, a rare recessive or syndromic disorder,
is usually delayed. Peripheral blood smear is extremely useful for establishing
the suspicion of sitosterolemia. High-throughput sequencing technology enables
the molecular diagnosis of inherited thrombocytopenias. Accurate characterization
of sitosterolemia helps us determine appropriate management. SUMMARY: Background
Sitosterolemia (STSL) is a recessive inherited disorder caused by pathogenic
variants in the ABCG5 and ABCG8 genes. Increased levels of plasma plant sterols
(PSs) usually result in xanthomas and premature coronary atherosclerosis,
although hematologic abnormalities may occasionally be present. This clinical
picture is unfamiliar to many physicians, and patients may be at high risk of
misdiagnosis. Objectives To report two novel ABCG5 variants causing STSL in a
Spanish patient, and review the clinical and mutational landscape of STSL.
Patient/Methods A 46-year-old female was referred to us with lifelong
macrothrombocytopenia. She showed familial hypercholesterolemia-related
xanthomas. Molecular analysis was performed with high-throughput sequencing.
Plasma PS levels were evaluated with gas-liquid chromatography. The STSL
landscape was reviewed with respect to specific online databases and all reports
published since 1974. Results A blood smear revealed giant platelets and
stomatocytes. Novel compound heterozygous variants were detected in exons 7
(c.914C>G) and 13 (c.1890delT) of ABCG5. The patient showed an increased plasma
level of sitosterol. These findings support the diagnosis of STSL. In our review,
we identified only 25 unrelated STLS patients who presented with hematologic
abnormalities including macrothrombocytopenia. It remains unknown why only some
patients develop hematologic abnormalities. Conclusions This is the first Spanish
STSL patient to be reported and molecularly characterized. The early diagnosis of
STLS is strongly supported by the presence of stomatocytes in blood smears. The
definitive diagnosis of STSL by measurement of serum PS levels and molecular
analyses prompted the use of ezetimibe therapy.
PMID- 28696551
TI - Sorting without a Golgi complex.
AB - The endoplasmic reticulum-Golgi-target organelle route is one of the most studied
events and has fascinated researchers for years. However, the conservative
mechanism of protein sorting and delivery is now being challenged by the finding
of unconventional pathways driving protein sorting and transport. Protozoa
parasites are being rediscovered as good models for analyzing alternative
targeting pathways, associated with their ability to adapt to diverse
environments and hosts. Here, we have gathered all the available information
about secretory protein trafficking in Giardia lamblia, with a focus on how this
protozoan parasite is able to sort and direct proteins to different compartments
in the absence of a Golgi complex.
PMID- 28696552
TI - Clinical experience with a single-nucleotide polymorphism-based non-invasive
prenatal test for five clinically significant microdeletions.
AB - Single-nucleotide polymorphism (SNP)-based non-invasive prenatal testing (NIPT)
can currently predict a subset of submicroscopic abnormalities associated with
severe clinical manifestations. We retrospectively analyzed the performance of
SNP-based NIPT in 80 449 referrals for 22q11.2 deletion syndrome and 42 326
referrals for 1p36, cri-du-chat, Prader-Willi, and Angelman microdeletion
syndromes over a 1-year period, and compared the original screening protocol with
a revision that reflexively sequenced high-risk calls at a higher depth of read.
The prevalence of these microdeletion syndromes was also estimated in the
referral population. The positive predictive value of the original test was 15.7%
for 22q11.2 deletion syndrome, and 5.2% for the other 4 disorders combined. With
the revised protocol, these values increased to 44.2% for 22q11.2 and 31.7% for
the others. The 0.33% false-positive rate (FPR) for 22q11.2 deletion syndrome
decreased to 0.07% with the revised protocol. Similarly, the FPR for the other 4
disorders combined decreased from 0.56% to 0.07%. Minimal prevalences were
estimated to be 1 in 1255 for 22q11.2 deletion syndrome and 1 in 1464 for 1p36,
cri-du-chat, and Angelman syndromes combined. Our results show that these
microdeletions are relatively common in the referral population, and that the
performance of SNP-based NIPT is improved with high-depth resequencing.
PMID- 28696553
TI - Mechanisms of the Diterpene Cyclases beta-Pinacene Synthase from Dictyostelium
discoideum and Hydropyrene Synthase from Streptomyces clavuligerus.
AB - Two diterpene cyclases, one from the social amoeba Dictyostelium discoideum and
the other from the bacterium Streptomyces clavuligerus, with products containing
a Z-configured double bond between the original C2 and C3 of geranylgeranyl
diphosphate, were extensively investigated for their mechanisms through isotopic
labelling experiments. The participation of geranyllinalyl diphosphate, in
analogy to the role of linalyl and nerolidyl diphosphate for mono- and
sesquiterpene biosynthesis, as an intermediate towards diterpenes with a Z
configured C2=C3 double bond is discussed.
PMID- 28696554
TI - Solution-Grown CsPbBr3 /Cs4 PbBr6 Perovskite Nanocomposites: Toward Temperature
Insensitive Optical Gain.
AB - With regards to developing miniaturized coherent light sources, the temperature
insensitivity in gain spectrum and threshold is highly desirable. Quantum dots
(QDs) are predicted to possess a temperature-insensitive threshold by virtue of
the separated electronic states; however, it is never observed in colloidal QDs
due to the poor thermal stability. Besides, for the classical II-VI QDs, the gain
profile generally redshifts with increasing temperature, plaguing the device
chromaticity. Herein, this paper addresses the above two issues simultaneously by
embedding ligands-free CsPbBr3 nanocrystals in a wider band gap Cs4 PbBr6 matrix
by solution-phase synthesis. The unique electronic structures of CsPbBr3
nanocrystals enable temperature-insensitive gain spectrum while the lack of
ligands and protection from Cs4 PbBr6 matrix ensure the thermal stability and
high temperature operation. Specifically, a color drift-free stimulated emission
irrespective of temperature change (20-150 degrees C) upon two-photon pumping is
presented and the characteristic temperature is determined to be as high as ~260
K. The superior gain properties of the CsPbBr3 /Cs4 PbBr6 perovskite
nanocomposites are directly validated by a vertical cavity surface emitting laser
operating at temperature as high as 100 degrees C. The results shed light on
manipulating optical gain from the advantageous CsPbBr3 nanocrystals and
represent a significant step toward the temperature-insensitive frequency
upconverted lasers.
PMID- 28696555
TI - Copy-Number Variants Detection by Low-Pass Whole-Genome Sequencing.
AB - Emerging studies have demonstrated that whole-genome sequencing (WGS) is an
efficient tool for copy-number variants (CNV) detection, particularly in probe
poor regions, as compared to chromosomal microarray analysis (CMA). However, the
cost of testing is beyond economical for routine usage and the lengthy turn
around time is not ideal for clinical implementation. In addition, the demand for
computational resources also reduces the probability of clinical integration into
each laboratory. Herein, a protocol providing CNV detection from low-pass, whole
genome sequencing (0.25*) in a clinical laboratory setting is described. The cost
is reduced to less than $200 USD per sample and the turn-around time is within an
acceptable clinically workable time-frame (7 days). (c) 2017 by John Wiley &
Sons, Inc.
PMID- 28696556
TI - 1D Genome Sequencing on the Oxford Nanopore MinION.
AB - Today's short-read sequencing instruments can generate read lengths between 50 bp
and 700 bp depending on the specific instrument. These high-throughput sequencing
approaches have revolutionized genomic science, allowing hundreds of thousands of
full genomes to be sequenced, and have become indispensable tools for many
researchers. With greater insight has come the revelation that many genomes are
much more complicated than originally thought and include many rearrangements and
copy-number variations. Unfortunately, short-read sequencing technologies are not
well suited for identifying many of these types of events. Long-read sequencing
technologies can read contiguous fragments of DNA in excess of 10 kb and are much
better suited for detecting large structural events. The newest long-read
sequencing instrument is the MinION device from Oxford Nanopore. The rapid
sequencing speed and low upfront instrument cost are features drawing interest in
this device from the genomics community. This unit provides a representative
protocol for carrying out human genome sequencing on the Oxford Nanopore MinION.
(c) 2017 by John Wiley & Sons, Inc.
PMID- 28696557
TI - Microscopy and Image Analysis.
AB - This unit provides an overview of light microscopy, including objectives, light
sources, filters, film, and color photography for fluorescence microscopy and
fluorescence in situ hybridization (FISH). We believe there are excellent
opportunities for cytogeneticists, pathologists, and other biomedical readers, to
take advantage of specimen optical clearing techniques and expansion microscopy
we briefly point to these new opportunities. (c) 2017 by John Wiley & Sons, Inc.
PMID- 28696558
TI - Mammalian Cell Tissue Culture.
AB - Cultured mammalian cells are used extensively in the field of human genetics. It
requires a number of special skills in order to be able to preserve the
structure, function, behavior, and biology of the cells in culture. This unit
describes the basic skills required to maintain and preserve cell cultures:
maintaining aseptic technique, preparing media with the appropriate
characteristics, passaging, freezing and storage, recovering frozen stocks, and
counting viable cells. (c) 2017 by John Wiley & Sons, Inc.
PMID- 28696559
TI - Genetic Testing for Hereditary Nonpolyposis Colorectal Cancer (HNPCC).
AB - Hereditary nonpolyposis colorectal cancer (HNPCC), also called Lynch syndrome, is
an autosomal dominant cancer syndrome that confers an elevated risk of early
onset colorectal cancer (CRC) and increased lifetime risk for other cancers of
the endometrium, stomach, small intestine, hepatobiliary system, kidney, ureter,
and ovary. Lynch syndrome accounts for up to 3% of all CRC, making it the most
common hereditary colorectal cancer syndrome. Germline mutations in methyl
directed mismatch repair (MMR) genes give rise to microsatellite instability
(MSI) in tumor DNA. Lynch syndrome is most frequently caused by pathogrenic
variants in the mismatch repair genes MLH1, MSH2, MSH6, and PMS2. Germline
mutations in MLH1 and MSH2 account for approximately 90% of detected mutations in
families with Lynch syndrome. Pathogenic vatiants in MSH6 have been reported in
approximately 7-10% of families with Lynch syndrome. Pathogenic variants in PMS2
account for fewer than 5% of mutations in families with Lynch syndrome. This unit
presents a comprehensive molecular genetic testing strategy for Lynch syndrome
including MSI analysis, next generation sequencing (NGS)-based targeted sequence
analysis, PCR-based Sanger sequencing and microarray-based comparative genomic
hybridization (array-CGH). (c) 2017 by John Wiley & Sons, Inc.
PMID- 28696560
TI - Overview of Admixture Mapping.
AB - Admixture mapping is a powerful method of gene mapping for diseases or traits
that show differential risk by ancestry. Admixture mapping has been applied most
often to Americans who trace ancestry to various combinations of Native
Americans, Europeans, and West Africans. Recent developments in admixture mapping
include improvements in methods and the reference data needed to make inferences
about ancestry, as well as extensions of the mapping approach in the framework of
linear mixed models. In this unit, the key concepts of admixture mapping are
outlined. Several approaches for inferring local ancestry are described, and
strategies for performing admixture mapping depending on the study design are
provided. Finally, comparisons and contrasts between linkage analysis,
association analysis, and admixture mapping are provided, with an emphasis on
integrating admixture mapping and association testing. (c) 2017 by John Wiley &
Sons, Inc.
PMID- 28696561
TI - A Solar-Blind UV Detector Based on Graphene-Microcrystalline Diamond
Heterojunctions.
AB - An ultraviolet detector is demonstrated through a whole-wafer, thin diamond film
transfer process to realize the heterojunction between graphene and
microcrystalline diamond (MCD). Conventional direct transfer processes fail to
deposit graphene onto the top surface of the MCD film. However, it is found that
the 2 um thick MCD diamond film can be easily peeled off from the growth silicon
substrate to expose its smooth backside for the graphene transfer process for
high-quality graphene/MCD heterojunctions. A vertical graphene/MCD/metal
structure is constructed as the photodiode device using graphene as the
transparent top electrode for solar-blind ultraviolet sensing with high
responsivity and gain factor. As such, this material system and device
architecture could serve as the platform for next-generation optoelectronic
systems.
PMID- 28696562
TI - Association between non-alcoholic fatty liver disease and peripheral artery
disease in patients with type 2 diabetes.
AB - BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is associated with the risk
of coronary heart diseases; however, the relationship between NAFLD and
peripheral artery disease (PAD) in patients with type 2 diabetes has not been
investigated. AIM: To investigate the association between NAFLD and PAD in
patients with type 2 diabetes. METHODS: We carried out a cross-sectional study on
2646 type 2 diabetes patients >= 40 years. All patients provided fasting blood
samples and underwent a liver ultrasonography and ankle-brachial index (ABI)
test. PAD was defined as an ABI <0.9. Multiple logistic regression analyses were
performed to investigate the odds ratio (OR) for PAD associated with NAFLD.
RESULTS: Our analyses showed that patients with NAFLD had a significantly higher
prevalence of PAD compared with those without NAFLD (12.8% vs 7.8%). NAFLD was
associated with a 75% (OR 1.75, 95% confidence interval (CI) 1.35-2.28) increased
risk of PAD after adjustment for demographic factors. Addition of various
metabolic risk factors as confounders attenuated the association (OR 1.49, 95% CI
1.12-2.00). Further adjustment for C-reactive protein led the association to be
marginally significant (OR 1.33, 95% CI 0.99-1.80). Analyses stratified by gender
suggested the association was much stronger among women than among men.
CONCLUSION: Type 2 diabetes patients with NAFLD had a higher prevalence of PAD,
and this association was partly, but not entirely, explained by metabolic risk
factors and inflammation.
PMID- 28696563
TI - Secondary Traumatization and Differentiation Among the Wives of Former POWs: A
Reciprocal Association.
AB - Repercussions of war captivity may transmit to spouses of former prisoners of war
(POW) via posttraumatic stress symptoms (PTSS). Overidentification with their
partners underlies the PTSS experienced by former wives of POWs, thus implying
impaired self-differentiation. Although wives' indirect exposure to their
husbands' captivity and subsequent PTSS has been associated with the wives' PTSS
and differentiation, the combined effects remain unclear. Furthermore, previous
cross-sectional studies could not illuminate directionality. This prospective
study investigates (a) the moderating role of indirect exposure to captivity in
the association between husbands' PTSS and wives' PTSS and differentiation; and
(b) the directionality of the association between wives' differentiation and PTSS
over time. The wives of both former POWs (n = 143) and combatants (n = 102) were
assessed 30 (T1) and 38 (T2) years after the 1973 Yom Kippur War. The wives of
former POWs endorsed higher PTSS and fusion differentiation, eta2p = .06 to .14.
Indirect exposure to captivity moderated the associations between husbands' PTSS
and wives' PTSS, Cohen's f2 = .01 to .03. The association between the wives'
differentiation and PTSS over time was bidirectional, beta = -0.18 to 0.68; R2 =
.54 to .73. Results suggest a vicious cycle between PTSS and differentiation, and
the need for clinical interventions that further differentiation for spouses of
prolonged trauma victims.
PMID- 28696564
TI - Microstructure Design of Lightweight, Flexible, and High Electromagnetic
Shielding Porous Multiwalled Carbon Nanotube/Polymer Composites.
AB - Multiwalled carbon nanotube/polymer composites with aligned and isotropic
micropores are constructed by a facile ice-templated freeze-drying method in a
wide density range, with controllable types and contents of the nanoscale
building blocks, in order to tune the shielding performance together with the
considerable mechanical and electrical properties. Under the mutual promotion of
the frame and porous structure, the lightweight high-performance shielding is
achieved: a 2.3 mm thick sample can reach 46.7 and 21.7 dB in the microwave X
band while the density is merely 32.3 and 9.0 mg cm-3 , respectively. The lowest
density corresponds to a value of shielding effectiveness divided by both the
density and thickness up to 104 dB cm2 g-1 , far beyond the conductive polymer
composites with other fillers ever reported. The shielding mechanism of the
flexible porous materials is further demonstrated by an in situ compression
experiment.
PMID- 28696565
TI - Endoplasmic reticulum is the sorting core facility in the Golgi-lacking protozoan
Giardia lamblia.
AB - Our understanding of protein and lipid trafficking in eukaryotic cells has been
challenged by the finding of different forms of compartmentalization and cargo
processing in protozoan parasites. Here, we show that, in the absence of a Golgi
compartment in Giardia, proteins destined for secretion are directly sorted and
packaged at specialized ER regions enriched in COPII coatomer complexes and
ceramide. We also demonstrated that ER-resident proteins are retained at the ER
by the action of a KDEL receptor, which, in contrast to other eukaryotic KDEL
receptors, showed no interorganellar dynamic but instead acts specifically at the
limit of the ER membrane. Our study suggests that the ER-exit sites and the
perinuclear ER-membranes are capable of performing protein-sorting functions. In
our view, the description presented here suggests that Giardia adaptation
represents an extreme example of reductive evolution without loss of function.
PMID- 28696566
TI - Super-resolution imaging of subcortical white matter using stochastic optical
reconstruction microscopy (STORM) and super-resolution optical fluctuation
imaging (SOFI).
AB - AIMS: The spatial resolution of light microscopy is limited by the wavelength of
visible light (the 'diffraction limit', approximately 250 nm). Resolution of sub
cellular structures, smaller than this limit, is possible with super resolution
methods such as stochastic optical reconstruction microscopy (STORM) and super
resolution optical fluctuation imaging (SOFI). We aimed to resolve subcellular
structures (axons, myelin sheaths and astrocytic processes) within intact white
matter, using STORM and SOFI. METHODS: Standard cryostat-cut sections of
subcortical white matter from donated human brain tissue and from adult rat and
mouse brain were labelled, using standard immunohistochemical markers
(neurofilament-H, myelin-associated glycoprotein, glial fibrillary acidic
protein, GFAP). Image sequences were processed for STORM (effective pixel size 8
32 nm) and for SOFI (effective pixel size 80 nm). RESULTS: In human, rat and
mouse, subcortical white matter high-quality images for axonal neurofilaments,
myelin sheaths and filamentous astrocytic processes were obtained. In
quantitative measurements, STORM consistently underestimated width of axons and
astrocyte processes (compared with electron microscopy measurements). SOFI
provided more accurate width measurements, though with somewhat lower spatial
resolution than STORM. CONCLUSIONS: Super resolution imaging of intact cryo-cut
human brain tissue is feasible. For quantitation, STORM can under-estimate
diameters of thin fluorescent objects. SOFI is more robust. The greatest
limitation for super-resolution imaging in brain sections is imposed by sample
preparation. We anticipate that improved strategies to reduce autofluorescence
and to enhance fluorophore performance will enable rapid expansion of this
approach.
PMID- 28696567
TI - Transplantation of amniotic membrane for choroidal hole to treat suprachoroidal
silicone oil migration.
PMID- 28696568
TI - Reproducibility of studies with genetically modified mice.
PMID- 28696569
TI - Reply to "Molecular mechanics models for the image charge".
AB - We have considered the system investigated by Steinmann et al. by means of the
image charge model originally proposed in Iori and Corni, J. Comput. Chem. 2008,
29, 1656. Qualitatively correct results are obtained, that compare favorably with
the relevant analytical benchmarks. We show that the effect of the asymmetry of
the rod model can be controlled, when needed, as originally suggested, that is,
by shorter rods. This strategy does not increase neither the complexity of the
model nor its computational cost. (c) 2017 Wiley Periodicals, Inc.
PMID- 28696570
TI - Effects of Combined Lysosomal and Mitochondrial Photodamage in a Non-small-Cell
Lung Cancer Cell Line: The Role of Paraptosis.
AB - We previously reported that a low level of lysosomal photodamage potentiated the
phototoxic effect of subsequent mitochondrial photodamage mediated by the
benzoporphyrin derivative (BPD) in murine hepatoma 1c1c7 cells. This was
attributed to release of Ca2+ from damaged lysosomes and a calpain-mediated
conversion of the autophagy-related protein ATG5 to a pro-apoptotic fragment. We
now report a comparison of these results with those obtained with the human non
small-cell lung cancer A549 cell line. A549 cells contained lower levels of ATG5
and were less responsive than 1c1c7 cultures to the PDT combination. A rapid
appearance of caspase 3/7 activation together with formation of condensed
chromatin indicated initiation of apoptosis in both cell lines, but to a lesser
extent in A549 cultures. Both cell lines became highly vacuolated within 16 h of
combination PDT or an equivalent phototoxic dose from BPD alone. The vacuole
periphery was labeled with a fluorescent probe for the endoplasmic reticulum
(ER), and vacuole formation was prevented by presence of the protein synthesis
inhibitor cycloheximide. These effects are characteristics of a caspase
independent death mode termed paraptosis previously associated with ER stress.
These studies suggest that paraptosis may be a more frequent outcome of PDT than
has hitherto been realized.
PMID- 28696571
TI - Acute evaluation of the acute vestibular syndrome: differentiating posterior
circulation stroke from acute peripheral vestibulopathies.
AB - This review article aims to provide an evidence-based approach to evaluating the
patient who presents with acute prolonged, spontaneous vertigo in the context of
the acute vestibular syndrome (AVS). Differentiation of posterior circulation
stroke (PCS) presenting as an AVS has been regarded as an important diagnostic
challenge for physicians involved in acute care. Current evidence suggests that a
targeted approach to history taking and physical examination with emphasis on the
oculomotor examination, more specifically the HINTS (Head Impulse/Nystagmus/Test
of-skew) examination battery, yields a higher sensitivity for the diagnosis of
PCS than even standard magnetic resonance imaging with diffusion-weighted
imaging. However, most studies have only validated the utility of the HINTS
examination when performed by experts, who interpret the most powerful component
of HINTS, namely the head impulse test (HIT), considerably different to the
novice. Several investigations useful in the differentiation of the AVS are
becoming more accessible and portable, such as videooculography with Frenzel
goggles and video head impulse testing (vHIT), which allows for the quantitative
assessment of the HIT. In clinical practice, vHIT has already become accepted as
standard of care in the evaluation of AVS.
PMID- 28696572
TI - Evaluation of Electrical Impedance Spectroscopy-on-a-Needle as a Novel Tool to
Determine Optimal Surgical Margin in Partial Nephrectomy.
AB - A hypodermic needle has been introduced incorporating an electrical impedance
spectroscopy (EIS) sensor, called micro-EIS-on-a-needle for depth profiling
(MUEoN-DP). The MUEoN-DP can locate endophytic renal tumors as well as determine
tumor margins by detecting the impedance difference between normal and cancer
tissues. To evaluate the MUEoN-DP as a novel tool to determine the optimal
surgical margin during partial nephrectomy (PN), the electrical impedance
differences between renal parenchymal tissues and renal cell carcinoma (RCC)
tumors are investigated with regard to the distance from the tumors. Optimal
frequencies at which the discrimination extent is maximized are suggested based
on the discrimination index. The resistance and capacitance of normal and cancer
tissues are extracted using electrical equivalent circuit by excluding the
influences of other electrical components on the sensor output. The extracted
resistance and capacitance of cancer tissues are 37.8% larger and 25.7% smaller
than that of normal tissues, respectively. Additionally, high sensitivity and
specificity are obtained by using extracted resistance and capacitance, thus
implying that the MUEoN-DP shows promise as a supplementary tool for PN margin
evaluation and decreasing the prevalence of positive surgical margins while
maximizing parenchymal preservation.
PMID- 28696573
TI - Prognostic implications of Q waves at presentation in patients with ST-segment
elevation myocardial infarction undergoing primary percutaneous coronary
intervention: An analysis of the HORIZONS-AMI study.
AB - BACKGROUND: Presence of Q waves on the presenting electrocardiogram (ECG) in
patients with ST-segment elevation myocardial infarction (STEMI) has been
associated with worse prognosis; however, whether the prognostic value of Q waves
is influenced by baseline characteristics and/or rapidity of revascularization
based on the guideline-based metric of door-to-balloon time remains unknown.
HYPOTHESIS: We hypothesized that Q waves in the presenting ECG will be predictive
of long term mortality regardless of time to reperfusion. METHODS: The
Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial
Infarction (HORIZONS-AMI) trial enrolled 3602 patients with STEMI undergoing
primary percutaneous coronary intervention. We stratified patients without prior
history of myocardial infarction or coronary revascularization according to
presence or absence of pathological Q waves on their presenting ECG. Associations
between Q waves, death, and cardiovascular outcomes within 3 years were assessed
using Cox proportional hazards regression. RESULTS: Among 2723 patients with
evaluable ECGs, 1084 (39.8%) had Q waves on their presenting ECG. Male sex and
time from symptom onset to balloon inflation were independent predictors of
presence of Q waves. Patients with Q waves had higher adjusted risks of all-cause
death (adjusted hazard ratio: 1.45, 95% confidence interval: 1.02-2.05, P = 0.04)
and cardiac death (adjusted hazard ratio: 1.72, 95% confidence interval: 1.08
2.72, P = 0.02). The association between Q waves and cardiac death was consistent
regardless of sex, diabetes status, target vessel, or door-to-balloon time
(Pinteraction > 0.4 for all). CONCLUSIONS: Presence of Q waves on the presenting
ECG in patients undergoing primary percutaneous coronary intervention due to
STEMI is an independent predictor of mortality and adds prognostic value,
regardless of sex or rapidity of revascularization.
PMID- 28696574
TI - Divergent Asymmetric Synthesis of Polycyclic Compounds via Vinyl Triazenes.
AB - Vinyl triazenes were obtained by enantioselective [2+2] cycloaddition reactions
of bicyclic alkenes with 1-alkynyl triazenes in the presence of a RuII catalyst
with a chiral cyclopentadienyl ligand. These triazenes serve as unique vinyl
cation surrogates. Under acidic conditions, the triazene functionality can be
replaced with a variety of groups, including halides, alkoxides, sulfoxides,
amides, arenes, and heteroarenes, thus providing efficient access to a pool of
chiral polycyclic compounds.
PMID- 28696575
TI - Impact of pulmonary rehabilitation on postoperative complications in patients
with lung cancer and chronic obstructive pulmonary disease.
AB - BACKGROUND: Given the extent of the surgical indications for pulmonary lobectomy
in breathless patients, preoperative care and evaluation of pulmonary function
are increasingly necessary. The aim of this study was to assess the contribution
of preoperative pulmonary rehabilitation (PR) for reducing the incidence of
postoperative pulmonary complications in non-small cell lung cancer (NSCLC)
patients with chronic obstructive pulmonary disease (COPD). METHODS: The records
of 116 patients with COPD, including 51 patients who received PR, were
retrospectively analyzed. Pulmonary function testing, including slow vital
capacity (VC) and forced expiratory volume in one second (FEV1 ), was obtained
preoperatively, after PR, and at one and six months postoperatively. The recovery
rate of postoperative pulmonary function was standardized for functional loss
associated with the different resected lung volumes. Propensity score analysis
generated matched pairs of 31 patients divided into PR and non-PR groups.
RESULTS: The PR period was 18.7 +/- 12.7 days in COPD patients. Preoperative
pulmonary function was significantly improved after PR (VC 5.3%, FEV1 5.5%; P <
0.05). The FEV1 recovery rate one month after surgery was significantly better in
the PR (101.6%; P < 0.001) than in the non-PR group (93.9%). In logistic
regression analysis, predicted postoperative FEV1 , predicted postoperative %FEV1
, and PR were independent factors related to postoperative pulmonary
complications after pulmonary lobectomy (odds ratio 18.9, 16.1, and 13.9,
respectively; P < 0.05). CONCLUSIONS: PR improved the recovery rate of pulmonary
function after lobectomy in the early period, and may decrease postoperative
pulmonary complications.
PMID- 28696576
TI - NAD(P)H and Flavin Autofluorescence Correlation with ATP in Rat Livers with
Different Metabolic Steady-State Conditions.
AB - The monitoring of NAD(P)H and flavin autofluorescence (AF) is at the basis of
numerous investigations on energy metabolism. Nevertheless, the ability of these
AF biomarkers to accurately represent the energy currency, ATP, is poorly
explored. Here, we focused on the AF/ATP correlation in lean and fatty livers
with different steady-state metabolic conditions, achieved after organ isolation,
preservation and recovery, in a likely dependence on both liver intrinsic
metabolic features and externally induced perturbations. Within these eventual,
various conditions, a significant correlation was detected between liver NAD(P)H
and flavin AF, measured via fiber-optic probe, and biochemical ATP data,
strengthening AF as biomarker of energy metabolism in steady-state conditions for
wide-ranging experimental and diagnostic applications.
PMID- 28696577
TI - Phototransformative Supramolecular Assembly of Amphiphilic Diarylethenes Realized
by a Combination of Photochromism and Lower Critical Solution Temperature
Behavior.
AB - Amphiphilic diarylethenes bearing octyloxycarbonyl and N-octylcarbamoyl groups
have been designed and synthesized. These ester- and amide-linked compounds form
micrometer-sized supramolecular assemblies in water, and these assemblies exhibit
photoinduced macroscopic morphological transformations upon alternate irradiation
with UV and visible light. The ester-linked diarylethene showed a transformation
between colorless spheres and a red-purple hazy fringe, whereas the microspheres
of the amide-linked diarylethene showed changes in color, size, and shape, but
the spheres did not show division. TEM images revealed that the spheres of the
open-ring isomers have coacervate structures, with bicontinuous aqueous and
organic phases. The closed-ring isomers of the ester- and amide-linked compounds
were found to form nanofibers and thin layers, respectively. These compounds
showed absorption spectral shifts at temperatures corresponding to the lower
critical solution temperature (LCST) transition. This morphological
transformation can be rationalized as the photoinduced phase transition between
the high- and low-temperature phases of the LCST transition. These results open
up a new avenue for the design of phototransformative supramolecular assemblies
based on a combination of photochromism and LCST behavior.
PMID- 28696578
TI - Does education modify the effect of ethnicity in the expression of ideal
cardiovascular health? The Baptist Health South Florida Employee Study.
AB - BACKGROUND: Despite the progress made to decrease risk factors for cardiovascular
diseases, disparities still exist. We examined how education and ethnicity
interact to determine disparities in cardiovascular health (CVH) as defined by
the American Heart Association. HYPOTHESIS: Education modifies the effect of
ethnicity on CVH. METHODS: Individual CVH metrics (smoking, physical activity,
body mass index, diet, total cholesterol, blood pressure, and blood glucose) were
defined as ideal, intermediate, or poor. Combined scores were categorized as
inadequate, average, or optimal CVH. Education was categorized as postgraduate,
college, some college, and high school or less; ethnicity was categorized as
white, Hispanic, black, and other. Main and interactive associations between
education, ethnicity, and the measures of CVH were calculated with multinomial
logistic regression. RESULTS: Of 9056 study participants, 74% were women, and
mean age was 43 (+/-12) years. Over half were Hispanic, and two-thirds had at
least a college education. With postgraduate education category as the reference,
participants with less than a college education were less likely to achieve ideal
status for most of the individual CVH metrics, and also less likely to achieve 6
to 7 ideal metrics, and optimal CVH scores. In most of the educational
categories, Hispanic participants had the highest proportion with optimal CVH
scores and 6 to 7 ideal metrics, whereas black participants had the lowest
proportion. However, there were no statistically significant interactions of
education and ethnicity for ideal CVH measures. CONCLUSIONS: Higher educational
attainment had variable associations with achieved levels of ideal CVH across
race/ethnic groups. Interventions to improve CVH should be tailored to meet the
needs of target communities.
PMID- 28696579
TI - Scrotal insulation and sperm production in the boar.
AB - Seasonal infertility is a limiting factor in boar fertility, and is increasingly
important as climate changes. Spermatogenesis in the boar produces 256
spermatozoa per type A1 spermatogonium, but the process is inefficient such that
only 10-30% of these potential spermatozoa are actually produced. Heat further
impacts spermatogenesis by reducing the number of specific germ cells produced
while increasing the fraction of abnormal sperm. Early studies used whole-animal
exposure to simulate seasonal exposure to heat under production settings, but
this approach is associated with many confounding factors that make assessment of
the mechanisms of heat-induced damage to spermatogenesis difficult. Scrotal
insulation provides a better model to investigate the mechanisms and potential
mitigation strategies of heat-induce damage. For example, scrotal insulation
helped identify a link between short-term heat stress and damage to meiotic germ
cells. This outcome is likely due to changes in the integrity of the blood-testis
barrier, which induce apoptosis, autophagy and DNA damage in the germ cells.
Further understanding how heat damages spermatogenesis, and whether or not this
can be repaired, are crucial to mitigating heat effects on boars in production
settings.
PMID- 28696580
TI - Empowerment in adolescents and young adults with cancer: Relationship with health
related quality of life.
AB - BACKGROUND: The difficulties adolescents and young adults (AYAs) encounter during
a cancer experience may result in a reduction in or absence of empowerment. The
aims of the current study were to assess levels of empowerment and associated
(demographic, clinical, or psychological) factors and examine the association
between empowerment and health-related quality of life (HRQOL) among AYA patients
with cancer. METHODS: Patients aged 18 to 35 years at time of cancer diagnosis
and who were seen by 1 of the members of the specialized multidisciplinary AYA
team of the Radboud University Medical Center were invited to complete
questionnaires regarding empowerment; HRQOL; and sociodemographic, clinical, and
psychological characteristics (autonomy, coping, unmet social support needs, and
psychological distress). RESULTS: A total of 83 AYA patients completed the
questionnaires. The mean age of the participants at the time of diagnosis was
27.5 years. The vast majority had been treated with chemotherapy (86%), had a
more advanced stage of disease, and had completed treatment at the time of
participation (74%). The mean empowerment level was 154.1 (standard deviation,
17.8) with a range of 114 to 200. Multivariate analysis demonstrated that the
autonomy subscales of self-awareness (beta = .35), capacity for managing new
situations (beta = .19), and social support (beta = .35) were found to be
positively associated with empowerment. Coping difficulties (beta = -.19) were
found to be negatively associated with empowerment. Empowerment was independently
associated with physical (beta = .31), psychological (beta = .50), social (beta =
.39), religious (beta = .33), and total HRQOL (beta = .52; all P<.01).
CONCLUSIONS: Low levels of empowerment were associated with low levels of
autonomy and social support, female sex, and coping difficulties among AYA
patients with cancer. Recognizing these patients as candidates for empowerment
interventions ultimately could help to improve HRQOL in late adolescence and
young adulthood. Cancer 2017;123:4039-47. (c) 2017 The Authors. Cancer published
by Wiley Periodicals, Inc. on behalf of American Cancer Society. This is an open
access article under the terms of the Creative Commons Attribution-NonCommercial
License, which permits use, distribution and reproduction in any medium, provided
the original work is properly cited and is not used for commercial purposes.
PMID- 28696581
TI - Metal-like Band Structures of Ultrathin Si {111} and {112} Surface Layers
Revealed through Density Functional Theory Calculations.
AB - Density functional theory calculations have been performed on Si (100), (110),
(111), and (112) planes with tunable number of planes for evaluation of their
band structures and density of states profiles. The purpose is to see whether
silicon can exhibit facet-dependent properties derived from the presence of a
thin surface layer having different band structures. No changes have been
observed for single to multiple layers of Si (100) and (110) planes with a
consistent band gap between the valence band and the conduction band. However,
for 1, 2, 4, and 5 Si (111) and (112) planes, metal-like band structures were
obtained with continuous density of states going from the valence band to the
conduction band. For 3, 6, and more Si (111) planes, as well as 3 and 6 Si (112)
planes, the same band structure as that seen for Si (100) and (110) planes has
been obtained. Thus, beyond a layer thickness of five Si (111) planes at ~1.6 nm,
normal semiconductor behavior can be expected. The emergence of metal-like band
structures for the Si (111) and (112) planes are related to variation in Si-Si
bond length and bond distortion plus 3s and 3p orbital electron contributions in
the band structure. This work predicts possession of facet-dependent electrical
properties of silicon with consequences in FinFET transistor design.
PMID- 28696582
TI - Hierarchical 3D Cobalt-Doped Fe3 O4 Nanospheres@NG Hybrid as an Advanced Anode
Material for High-Performance Asymmetric Supercapacitors.
AB - Hierarchical nanostructure, high electrical conductivity, extraordinary specific
surface area, and unique porous architecture are essential properties in energy
storage and conversion studies. A new type of hierarchical 3D cobalt encapsulated
Fe3 O4 nanosphere is successfully developed on N-graphene sheet (Co-Fe3 O4 NS@NG)
hybrid with unique nanostructure by simple, scalable, and efficient solvothermal
technique. When applied as an electrode material for supercapacitors,
hierarchical Co-Fe3 O4 NS@NG hybrid shows an ultrahigh specific capacitance (775
F g-1 at a current density of 1 A g-1 ) with exceptional rate capability (475 F g
1 at current density of 50 A g-1 ), and admirable cycling performance (97.1%
capacitance retention after 10 000 cycles). Furthermore, the fabricated Co-Fe3 O4
NS@NG//CoMnO3 @NG asymmetric supercapacitor (ASC) device exhibits a high energy
density of 89.1 Wh kg-1 at power density of 0.901 kW kg-1 , and outstanding
cycling performance (89.3% capacitance retention after 10 000 cycles). Such
eminent electrochemical properties of the Co-Fe3 O4 NS@NG are due to the high
electrical conductivity, ultrahigh surface area, and unique porous architecture.
This research first proposes hierarchical Co-Fe3 O4 NS@NG hybrid as an ultrafast
charge-discharge anode material for the ASC device, that holds great potential
for the development of high-performance energy storage devices.
PMID- 28696583
TI - Mapping medical marijuana: state laws regulating patients, product safety, supply
chains and dispensaries, 2017.
AB - AIMS: (1) To describe open source legal data sets, created for research use, that
capture the key provisions of US state medical marijuana laws. The data document
how state lawmakers have regulated a medicine that remains, under federal law, a
Schedule I illegal drug with no legitimate medical use. (2) To demonstrate the
variability that exists across states in rules governing patient access, product
safety and dispensary practice. METHODS: Two legal researchers collected and
coded state laws governing marijuana patients, product safety and dispensaries in
effect on 1 February 2017, creating three empirical legal data sets. We used
summary tables to identify the variation in specific statutory provisions
specified in each state's medical marijuana law as it existed on 1 February 2017.
We compared aspects of these laws to the traditional Federal approach to
regulating medicine. Full data sets, codebooks and protocols are available
through the Prescription Drug Abuse Policy System (http://www.pdaps.org/;
Archived at http://www.webcitation.org/6qv5CZNaZ on 2 June 2017). RESULTS: Twenty
eight states (including the District of Columbia) have authorized medical
marijuana. Twenty-seven specify qualifying diseases, which differ across states.
All states protect patient privacy; only 14 protect patients against
discrimination. Eighteen states have mandatory product safety testing before any
sale. While the majority have package/label regulations, states have a wide range
of specific requirements. Most regulate dispensaries (25 states), with
considerable variation in specific provisions such as permitted product supply
sources number of dispensaries per state and restricting proximity to various
types of location. CONCLUSIONS: The federal ban in the United States on marijuana
has resulted in a patchwork of regulatory strategies that are not uniformly
consistent with the approach usually taken by the Federal government and whose
effectiveness remains unknown.
PMID- 28696584
TI - Size Effect on the Cytotoxicity of Layered Black Phosphorus and Underlying
Mechanisms.
AB - A systematic cytotoxicity study of layered black phosphorus (BP) is urgently
needed before moving forward to its potential biomedical applications. Herein,
bulk BP crystals are synthesized and exfoliated into layered BP with different
lateral size and thickness. The cytotoxicity of as-exfoliated layered BP is
evaluated by a label-free real-time cell analysis technique, displaying a
concentration-, size-, and cell type-dependent response. The IC50 values can vary
by 40 and 30 times among the BP sizes and cell types, respectively. BP-1 with the
largest lateral size and thickness has the highest cytotoxicity; whereas the
smallest BP-3 only shows moderate toxicity. The sensitivity of three tested cell
lines follows the sequence of 293T > NIH 3T3 > HCoEpiC. Two possible mechanisms
for BP to induce cytotoxicity are proposed and verified: (1) the generation of
intracellular reactive oxygen species (ROS) is detected by a ROS sensitive probe
using the inverted fluorescence microscopy and flow cytometry; (2) the
interaction of layered BP and model cell membrane is examined by quartz crystal
microbalance with dissipation, illustrating the disruption of cell membrane
integrity especially by the largest BP-1. This systematic study of BP's
cytotoxicity will shed light on its future biomedical and environmental
applications.
PMID- 28696585
TI - The presence and severity of nonalcoholic steatohepatitis is associated with
specific changes in circulating bile acids.
AB - : The histologic spectrum of nonalcoholic fatty liver disease (NAFLD) includes
fatty liver (NAFL) and steatohepatitis (NASH), which can progress to cirrhosis in
up to 20% of NASH patients. Bile acids (BA) are linked to the pathogenesis and
therapy of NASH. We (1) characterized the plasma BA profile in biopsy-proven NAFL
and NASH and compared to controls and (2) related the plasma BA profile to liver
histologic features, disease activity, and fibrosis. Liquid chromatography/mass
spectrometry quantified BAs. Descriptive statistics, paired and multiple group
comparisons, and regression analyses were performed. Of 86 patients (24 controls,
25 NAFL, and 37 NASH; mean age 51.8 years and body mass index 31.9 kg/m2 ), 66%
were women. Increased total primary BAs and decreased secondary BAs (both P <
0.05) characterized NASH. Total conjugated primary BAs were significantly higher
in NASH versus NAFL (P = 0.047) and versus controls (P < 0.0001). NASH had higher
conjugated to unconjugated chenodeoxycholate (P = 0.04), cholate (P = 0.0004),
and total primary BAs (P < 0.0001). The total cholate to chenodeoxycholate ratio
was significantly higher in NAFLD without (P = 0.005) and with (P = 0.02)
diabetes. Increased key BAs were associated with higher grades of steatosis
(taurocholate), lobular (glycocholate) and portal inflammation
(taurolithocholate), and hepatocyte ballooning (taurocholate). Conjugated cholate
and taurocholate directly and secondary to primary BA ratio inversely correlated
to NAFLD activity score. A higher ratio of total secondary to primary BA
decreased (odds ratio, 0.57; P = 0.004) and higher conjugated cholate increased
the likelihood of significant fibrosis (F>=2) (P = 0.007). CONCLUSION: NAFLD is
associated with significantly altered circulating BA composition, likely
unaffected by type 2 diabetes, and correlated with histological features of NASH;
these observations provide the foundation for future hypothesis-driven studies of
specific effects of BAs on specific aspects of NASH. (Hepatology 2017).
PMID- 28696586
TI - Novel Co2 VO4 Anodes Using Ultralight 3D Metallic Current Collector and Carbon
Sandwiched Structures for High-Performance Li-Ion Batteries.
AB - A novel spinel Co2 VO4 is studied as the Li-ion battery anode material and it is
sandwiched with a 3D ultralight porous current collector (PCC) and amorphous
carbon. Co2 VO4 demonstrates the high capacity and excellent cyclability because
of the mixed lithium storage mechanisms. The 3D composite structure requires no
binders and replaces the conventional current collector (Cu foil) with a 3D
ultralight porous metal scaffold, yielding the high electrode-based capacity.
Such a novel composite anode also enables the close adhesion of Co2 VO4 to the
PCC scaffold. The resulting monolithic electrode has the rapid electron pathway
and stable mechanical properties, which lead to the excellent rate capabilities
and cycling properties. At a current density of 1 A g-1 , the PCC and carbon
sandwiched Co2 VO4 anode is able to deliver a stable reversible capacity of about
706.8 mAh g-1 after 1000 cycles. Generally, this study not only develops a new
Co2 VO4 anode with high capacity and good cyclability, but also demonstrates an
alternative approach to improve the electrochemical properties of high capacity
anode materials by using ultralight porous metallic current collector instead of
heavy copper foil.
PMID- 28696587
TI - Toxicological terms - use and misuse - Part One.
PMID- 28696588
TI - Feedforward inhibition is randomly wired from individual granule cells onto CA3
pyramidal cells.
AB - Feedforward inhibition (FFI) between the dentate gyrus (DG) and CA3 sparsifies
and shapes memory- and spatial navigation-related activities. However, our
understanding of this prototypical FFI circuit lacks essential details, as the
wiring of FFI is not yet mapped between individual DG granule cells (GCs) and CA3
pyramidal cells (PCs). Importantly, theoretically opposite network contributions
are possible depending on whether the directly excited PCs are differently
inhibited than the non-excited PCs. Therefore, to better understand FFI wiring
schemes, we compared the prevalence of disynaptic inhibitory postsynaptic events
(diIPSCs) between pairs of individually recorded GC axons or somas and PCs, some
of which were connected by monosynaptic excitation, while others were not. If FFI
wiring is specific, diIPSCs are expected only in connected PCs; whereas diIPSCs
should not be present in these PCs if FFI is laterally wired from individual GCs.
However, we found single GC-elicited diIPSCs with similar probabilities
irrespective of the presence of monosynaptic excitation. This observation
suggests that the wiring of FFI between individual GCs and PCs is independent of
the direct excitation. Therefore, the randomly distributed FFI contributes to the
hippocampal signal sparsification by setting the general excitability of the CA3
depending on the overall activity of GCs.
PMID- 28696589
TI - In vitro activity of the interaction between taxifolin (dihydroquercetin) and
pyrimethamine against Toxoplasma gondii.
AB - Toxoplasmosis is one of the most neglected zoonotic foodborne parasitic diseases
that cause public health and socioeconomic concern worldwide. The current drugs
used for the treatment of toxoplasmosis have been identified to have clinical
limitations. Hence, new drugs are urgently needed to eradicate T.gondii
infections globally. Here, an in vitro anti-Toxoplasma gondii activity of
taxifolin (dihydroquercetin) and dihydrofolate inhibitor (pyrimethamine) alone
and in combination with a fixed concentration of pyrimethamine were investigated
against the rapidly proliferating T.gondii RH strain at 48 hr using colorimetric
assay. Pyrimethamine showed the highest anti-T. gondii activity with IC50P of
0.84 MUg/ml (p > .05), respectively. The combination of pyrimethamine with
dihydroquercetin gave a significant inhibitory activity against tachyzoites in in
vitro with IC50p of 1.39 MUg/ml (p < .05). The IC50p ranges obtained for the
individual and the combination of taxifolin with pyrimethamine inhibition of
parasite growth were not cytotoxic to the infected HFF and Hek-293 cell lines
used. These compounds combination should be investigated further using in vivo
model of toxoplasmosis.
PMID- 28696590
TI - Modulating the Cellular Immune Response of Oligonucleotides by Brush Polymer
Assisted Compaction.
AB - Unwanted stimulation of the innate immune system by foreign nucleic acids has
been one of the major barriers preventing bioactive sequences from reaching
market. Foreign nucleic acids can be recognized by multiple pattern recognition
receptors (PRRs), which trigger a signaling cascade to activate host defense
systems, leading to a range of side effects. This study demonstrates that
polyethylene glycol (PEG)-modified DNA strands can greatly reduce the activation
of the innate immune system, and the extent of reduction is dependent upon
polymer architecture. Highly branched brushes with long PEG side chains achieve
the best suppression by blocking PRR interactions via a local steric effect.
Interestingly, the brush polymer creates little barrier toward DNA-DNA
interaction. Quantification of inflammatory cytokines in both mRNA and protein
levels as well as the extent of cellular uptake shows a direct correlation
between steric congestion and reduction of cellular immune response. These
results suggest that the brush architecture offers unique advantages for
PEGylating oligonucleotides in the context of minimizing unwanted immune system
activation.
PMID- 28696591
TI - ?
PMID- 28696592
TI - [Update on the evaluation and management of dizziness in older people].
AB - This article provides an update on the evaluation and management of dizziness in
older people. It is based on a recent literature review. Indeed, it is a frequent
reason to consult a general practitioner. Its clinical presentation is not very
specific and its treatment is often challenging. Although dizziness is often
benign it can have serious physical, functional and psychological consequences.
Thanks to a careful medical history and simple clinical examination tools,
general practitioners can make a correct diagnosis and provide early
multidisciplinary care that can greatly improve the quality of life of elderly
people who suffer from dizziness.
PMID- 28696593
TI - [Sarcopenia in elderly : benefice of physical exercices].
AB - From the age of fifty onwards a progressive loss of muscle mass may be observed,
it often leads to real sarcopenia. Sedentary life style and unbalanced feeding
habits represent major risk factors. The decrease in muscle tone leads to a loss
of function and an altered quality of life, not to mention socioeconomic factors.
The molecular mechanisms of sarcopenia are complex but our understanding of them
is increasing. There is no pharmaceutical treatment of sarcopenia of use in
current practice. Regular, several times a week, practice of a combination of
adapted muscle building physical and endurance exercises, associated with protein
intake have shown there use. These exercises must be followed on the long term.
PMID- 28696594
TI - [Management of co-morbidities in demented patients].
AB - The interaction between co-morbidities and dementia is complex. Are co
morbidities dementia or age-related ? Does one die of dementia or with dementia ?
Presentation of illness is atypical in older populations but particularly so in
individuals with dementia. How should one then detect and measure the co
morbidity burden, what is the best management and the most ethically correct
approach to decision making ? We will discuss basic principles that can be
applied to ensure optimal care of co-morbidities in people with dementia with
some practical examples.
PMID- 28696595
TI - [Management of pneumonia in advanced stage dementia].
AB - Alzheimer's dementia is a leading cause of morbidity and mortality with
devastating consequences for the affected individuals and their family. Pneumonia
is a common complication in patients with advanced dementia that is frequently
the direct cause of death. Despite the relatively well-established progressive
and non-reversible trajectory of Alzheimer's disease, these patients still
frequently receive curative treatments during the last months of their lives and
access to palliative care is often delayed. The approach and therapeutic options
to manage pneumonia at the advanced stage of Alzheimer's disease are discussed in
this article.
PMID- 28696596
TI - [Anticoagulation in old fallers : a common challenge].
AB - Long term anticoagulation is required to reduce the risk of stroke or other
thromboembolic events resulting from atrial fibrillation. Thus, anticoagulation
is frequently considered in older persons who are at increased risk for
hemorrhagic adverse events. This is even more so as about a third of older
persons aged 65 years and over will fall over a year. Nevertheless, benefits from
risk reduction in stroke incidence and its consequences (functional depen-dency,
cognitive decline, altered quality of life, death) resulting from anticoagulant
prescription remains superior to its related risk.
PMID- 28696597
TI - [Sepsis : particularities in the elderly patients].
AB - Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated
host response to an infection. The clinical presentation of sepsis in the elderly
is very variable and sepsis is therefore challenging to diagnose in this
population. The new sepsis definitions published in 2016, which are based on
objective clinical and biological scores, should lead to earlier recognition and
diagnosis. Treatment should start as soon as possible because the specific
pathophysiological changes of aging increase the risk of a sudden deterioration
to septic shock. Physicians should treat elderly patients with sepsis according
to internationally recommended guidelines but should take into account specific
aspects related to the elderly. These aspects include the presence of specific
comorbidities and the need to clarify the overall objectives of care when
deciding to admit a patient to the intensive care unit.
PMID- 28696598
TI - [Patients with variations of sex development : an example of interdisciplinary
care].
AB - The medical, psychological and social aspects of disorders of sex development
(DSD) represent a challenge for the management of these patients. However,
advances in our understanding of the etiology and genetics of this condition,
novel surgical approaches and the growing influence of patient groups as well as
wider recognition of ethical issues have helped improve the care of patients with
a DSD. Importantly, a multidisciplinary approach involving specialists is crucial
for understanding and treating such rare and complex cases. According to the
recommendations of the Swiss National Ethical Commission, we shall use the term "
Variation of Sex Development " rather than " Disorder of Sex Development " in
this publication. This article addresses the care of DSD patients throughout
development from the point of view of specialists in complementary fields.
PMID- 28696599
TI - ?
PMID- 28696600
TI - ?
PMID- 28696601
TI - ?
PMID- 28696602
TI - ?
PMID- 28696604
TI - ?
PMID- 28696603
TI - ?
PMID- 28696605
TI - ?
PMID- 28696606
TI - [My patient will receive immunosuppressive therapy : which vaccination for each
situation ?]
AB - The number of patients whose immune responses are impaired is increasing over the
years due to larger use of immunosuppressive therapies aiming at treating
malignant, autoimmune or inflammatory diseases. These patients are at high risk
of infections, many of which are preventable by vaccination. However, this
population is often under-vaccinated because of negligence but also of concerns
regarding the safety of these vaccines, the potential risk of exacerbation of
underlying disease or vaccine efficacy. In this article, we are trying to
stratify different patient groups based on different immunosuppressive treatments
and to present adequate vaccination schemes according to the recommendations
found in medical literature.
PMID- 28696607
TI - [E-learning : an effective and necessary complement to the postgraduate
training].
AB - The evolution of modern medicine largely influenced the development of new
postgraduate training programs, which requirements are more engaging and
constraining. Time dedicated to education more and more often comes into
competition with the resident's clinical and administrative activities. In this
context, E-learning could be an interesting solution, if used complementary to
the classical training which does not further overload the clinical activity. By
focusing on the recognition of clinical images, and interpretation of functional
tests, we target some well known knowledge gaps of our trainees. Our program
allows every participant to be exposed to some important, prototypical or rare
situations, independent of the clinical exposure. The quality of our program is
ensured by the collaboration with several specialty departments of our hospital.
PMID- 28696608
TI - ?
PMID- 28696609
TI - [The role of medical autopsies as a quality control of patients management in
internal medicine units].
AB - The number of medical autopsies has declined in recent decades due to the
development of imaging techniques and some risks linked to autopsies. However,
the contribution of autopsy is diagnostically significant, even better than new
technologies currently available. It is thus a good indicator of quality, but
also a training tool, and has a significant impact in the grieving process. At
the CHUV, under the leadership of Pathology Department, institutional projects
have been implemented in order to increase the number of autopsies, including a
pre- and post-graduate training and systematic request for autopsy, with
significant gain for clinicians and pathologists, but also for families who get
systematic and customized return results.
PMID- 28696610
TI - [From incident-reporting to morbidity and mortality rounds].
AB - In 2015 a computer-based system of incident reporting was implemented in our
hospital. Since then our department has successfully managed this reporting
process with a constant interest shown by our staff (1 report / 100 days of
hospitalization which equals nearly 2 reports a day). All incidents are analyzed.
Some are then chosen for their impact and improvement potential and presented to
hospital staff at monthly morbidity and mortality (M&M) conferences or published
as clinical cases. This puts emphasis on the reporting process and on suggested
practical changes. The current challenge is to transform these ideas into daily
improvements and to find the necessary resources to report and analyze the more
complex incidents.
PMID- 28696611
TI - [Prevention of health care associated infections and bacterial resistance :
guidance for good practice].
AB - Despite improvement of infection control measures during the last 20 years,
incidence of health care associated infections (HAI) remains high. HAI, also
known as nosocomial infections, are mainly due to susceptible bacteria. However,
resistant bacteria are responsible for some of them. In Switzerland, methicillin
resistant Staphylococcus aureus incidence is decreasing but enterobacteriaceae
producing extended spectrum beta-lactamase are increasing. In addition, emerging
resistance challenges such as vancomycin-resistant enterococci or carbapenemase
producing bacteria were observed occasionally during recent years. Physicians in
charge of hospitalized patients should know and apply good practice measures to
prevent HAI and reduce the emergence and spread of multidrug resistant bacteria.
PMID- 28696612
TI - ?
PMID- 28696613
TI - ?
PMID- 28696614
TI - ?
PMID- 28696615
TI - ?
PMID- 28696617
TI - ?
PMID- 28696616
TI - ?
PMID- 28696618
TI - ?
PMID- 28696619
TI - ?
PMID- 28696620
TI - ?
PMID- 28696621
TI - [Genomic medicine : the challenges of information in clinical practice].
AB - The genomic revolution lifts up several potential opportunities in predictive and
preventive medicine. Yet, genomic medicine opportunities can lead to clinical
utility only if challenges that come with it are understood, anticipated, and
faced. This review discusses the challenges that genomic medicine raises for the
patients and their physicians, the general population, study participants and
investigators. The article presents a program of genomic consultation in general
internal medicine in the French-speaking part of Switzerland (MedOmics) that aims
to address these challenges in order to optimize the clinical opportunities
offered by genomic medicine.
PMID- 28696622
TI - [Exercise-referral to a specialist in adapted physical activity (APA) : a pilot
project].
AB - Family physicians have a key role in the promotion of physical activity, in
particular in identifying and counseling persons who have a sedentary lifestyle.
Some patients could benefit from intensive individual counseling. Physicians are
often not aware of all physical activity promotion activities in the community
that they could recommend their patients. In a pilot study, we have tested and
adapted the referral of patients from family physicians to specialists in adapted
physical activity (APAs). APAs are trained to assess and guide persons towards
physical activities adapted to their needs and pathologies and thus towards an
increase in physical activity. Pilot data suggest that, while few patients were
oriented to the APAs in the pilot project, family physicians appreciate the
possibility of collaborating with the APAs.
PMID- 28696623
TI - [Doctor : " I hurt everywhere "].
AB - Faced with diffuse pain, the doctor must evoke a wide range of pathologies. It is
necessary to think about rare illnesses such as myopathy or vasculitis, but also
more common illnesses such as fibromyalgia. Contrary to popular belief, it is
difficult to give a diagnosis of fibromyalgia, on average 2 years after the onset
of symptoms. This can be explained by heterogeneous complaints and the doctor
delaying the diagnosis with unnecessary complimentary examinations.Patient
education and physical activity are the most important steps of treatment. Few
drugs have proven effective and their use is limited due to significant side
effects. The evolution of fibromyalgia is chronic, with a mixed prognosis.
PMID- 28696624
TI - [It all started with a simple symptom and then... Basic palliative medical tools
for primary care physicians].
AB - The treatment of symptoms in palliative care is of primary importance, though
this in itself is not sufficient for the relief of all aspects of a patient's
suffering. Pain, dyspnea, or anxiety cannot be reduced to a single somatic
characteristic, the psychological implications and the consequences on the
patient's daily life being of paramount importance. A respect with regard to
certain basic principles, and a full knowledge of the main therapeutic approaches
available, allow for a better initial management of the symptoms.To this end we
propose references as a memory aid while pointing out that the apparition of
complex elements or instability in this type of case justifies having recourse to
a specialised structure.
PMID- 28696625
TI - [Examination of the abdomen, let's train again ?]
AB - This article describes the main clinical gestures to perform when a patient
complains of acute abdominal pain. It summarizes the knowledge in general
medicine by integrating whenever possible clinical reasoning with likelihood
ratios. This chapter does not address complex situations.
PMID- 28696626
TI - [Home visits by GPs - Considerations in Europe and in Switzerland].
AB - Home visits are essential for promoting the ability to remain at home and prevent
nursing home admissions ; general practitioners play a key role in the
development of this specific ambulatory care. Although the frequency of home
visits seems to be overall decreasing in recent years, they remain essential,
given the expected demographic changes. This is why education on home visits
should be introduced in the training of our students during early years. However,
there is a gap in literature regarding the optimal number and length of home
visits, as well as the kind of groups most likely to benefit from them and thus
more research is needed to enlighten these aspects of home visits.
PMID- 28696627
TI - ?
PMID- 28696628
TI - ?
PMID- 28696629
TI - ?
PMID- 28696630
TI - ?
PMID- 28696631
TI - ?
PMID- 28696632
TI - ?
PMID- 28696633
TI - ?
PMID- 28696634
TI - ?
PMID- 28696635
TI - [How to handle a non-resolving pneumonia?]
AB - Persistent pneumonias are frequent both in hospital and primary care settings.
Several parameters have to be taken into account. Firstly the appropriateness of
treatment; secondly the immune status of the host; and finally infectious
complications need to be ruled out. Several non-infectious diagnoses can mimic a
persistent infiltrate, such as neoplastic disorders, organising pneumonias,
interstitial disorders and drug - or radiation-induced lung diseases. Uncommon
pathogens will not respond to common treatment, for instance atypical bacteria,
mycobacteria, fungi including Pneumocystis as well as viruses. Referral to a
pulmonologist should be considered to perform a fiberoptic bronchoscopy.
PMID- 28696636
TI - [Update on multidrug resistant tuberculosis in Switzerland].
AB - Multi-resistant tuberculosis (MDR-TB) is a world-wide public-health problem with
about half a million cases/year (of a total of 9 million cases of TB). Patients
at highest risk for MDR-TB are those who have already been treated. Among other
risk factors are: contact with an index case of MDR-TB, being a migrant, and
originating from a country with a high incidence of MDR-TB. Switzerland has had
so far a relatively small number of MDR-TB cases, with a slight increase over the
past few years. Use of PCR and genotypic antibiograms allow a rapid detection of
MDR-TB cases as well as initiating a more adapted treatment, which must however
be finally adjusted on the basis of the phenotypic antibiogram. Treatment is
long, costly and tedious, even if, based on recent data, there is a hope for
shorter treatments (9-12 months).
PMID- 28696637
TI - [Eosinophilic pneumonia, how to differentiate: classification and diagnostic
approach].
AB - Eosinophilic pneumonia is characterized by pulmonary eosinophilia associated with
and/or alveolar eosinophilia. Furthermore, blood eosinophilia may be absent
particularly in patients who have benefited beforehand of corticosteroids. The
most common causes are parasites and drugs. According to the classification, we
distinguish idiopathic pneumonia with eosinophils, those related to vasculitis
and those of known etiology. Extrapulmonary involvement is frequently found in
the subgroup of vasculitis. It is important to diagnose and start treatment
quickly to reduce the risk of complications. The primary treatment is based on
corticosteroids and in severe cases of vasculitis immunosuppressants are
necessary.
PMID- 28696638
TI - [Update on the treatment of sarcoidosis].
AB - Sarcoidosis is a granulomatous disease characterized by variable manifestations
and course. About 50% of patients will require systemic treatment, while the
remaining will present spontaneous resolution of the disease. When a systemic
therapy is necessary, it is prolonged and relapse rate is high when it is
discontinued. Systemic corticosteroids are the first line treatment in
sarcoidosis. Because of many side effects, it is essential to consider other
drugs in case of intolerance to steroids, as steroid-sparing agents, or in case
of inefficiency of corticotherapy alone.
PMID- 28696639
TI - [Occupational asthma].
AB - Occupational asthma is the most common occupational respiratory disease. It
mainly affects young workers with significant socio-economic consequences. Early
recognition improves its prognosis. A rigorous investigative approach while the
worker is still exposed at work and appropriate medical care require a multi
disciplinary collaboration. Prevention is the key element in the management of
professional asthma.
PMID- 28696640
TI - [Subsolid pulmonary nodules].
AB - Subsolid nodules represent almost 20% of all pulmonary nodules found incidentally
at chest computed tomography (CT). Their detection is steadily rising, in
parallel with the increasing number of CT scans performed. Subsolid nodules
differ from solid lung nodules in several ways: morphology, course of
progression, risk of malignancy and prognosis. Although they remain a diagnostic
challenge, a good correlation has been established between radiological
appearance and histopathology. Whilst 75% of persistent subsolid nodules
represent a form of adenocarcinoma, their prognosis is generally excellent when
resected. Non-resected subsolid nodules require a long follow-up of 3 to 5 years
due to their slow-growing nature and high prevalence of malignancy. Specific
guidelines have been published in 2013 and in 2015.
PMID- 28696641
TI - ?
PMID- 28696642
TI - ?
PMID- 28696643
TI - ?
PMID- 28696644
TI - ?
PMID- 28696645
TI - ?
PMID- 28696646
TI - ?
PMID- 28696647
TI - ?
PMID- 28696648
TI - ?
PMID- 28696652
TI - Tuning Gas Adsorption Properties of Zeolite-like Supramolecular Assemblies with
gis Topology via Functionalization of Isoreticular Metal-Organic Squares.
AB - A strategy based on metal-ligand directed assembly of metal-organic squares
(MOSs), built-up from four-membered ring (4MR) secondary building units (SBUs),
has been employed for the design and construction of isoreticular zeolite-like
supramolecular assemblies (ZSAs). Four porous Co-based ZSAs having the same
underlying gis topology, but differing only with respect to the capping and
bridging linkers, were successfully isolated and fully characterized. In this
series, each MOS in ZSA-3-ZSA-6 possess an ideal square geometry and is connected
to four neighboring MOS via a total of 16 hydrogen bonds to give a 3-periodic
porous network.To systematically assess the effect of the pore system (size and
functionality) on the gas adsorption properties, we evaluated the MOSs for their
affinity for different probe molecules such as CO2 and light hydrocarbons. ZSA-3
ZSA-6 showed high thermal stability (up to 300 degrees C) and was proven highly
porous as evidenced by gas adsorption studies. Notably, alkyl-functionalized MOSs
were found to offer potential for selective separation of CO2, C3H6, and C3H8
from CH4 and H2 containing gas stream, such as natural gas and refinery-off
gases.
PMID- 28696653
TI - Nanopatterned Adhesive, Stretchable Hydrogel to Control Ligand Spacing and
Regulate Cell Spreading and Migration.
AB - Spatial molecular patterning enables the regulation of adhesion receptor
clustering and can thus play a pivotal role in multiple biological activities
such as cell adhesion, viability, proliferation, and differentiation. A wide
range of nanopatterned, adhesive interfaces have been designed to decipher the
essence of molecular-scale interactions between cells and the adhesive interface.
Although an interligand spacing of less than 70 nm is a proven prerequisite for
the formation of stable focal adhesions, there is a paucity of data concerning
how cells behave on substrates featuring heterogeneous adhesiveness. In this
study, a stretchable hydrogel functionalized with a quasi-hexagonally arranged
nanoarray was stretched along one direction, resulting in ligands periodically
arranged in a pattern resembling a centered rectangular lattice with an
interligand spacing smaller than 70 nm in one direction and greater than 70 nm in
the orthogonal direction. This substrate was utilized to modulate interligand
spacing and investigate cell adhesion and migration. An interligand spacing
larger than 70 nm-even in just one direction-prevented the establishment of
stable focal adhesions. The stretched interface promoted dynamic remodeling at
cell contacts, resulting in higher cellular mobility. Our nanopatterned
stretchable hydrogel permits reversible control over cell adhesion and migration
on nanopatterned ligand interfaces.
PMID- 28696654
TI - High-Temperature Stable Anatase Titanium Oxide Nanofibers for Lithium-Ion Battery
Anodes.
AB - Control of the crystal structure of electrochemically active materials is an
important approach to fabricating high-performance electrodes for lithium-ion
batteries (LIBs). Here, we report a methodology for controlling the crystal
structure of TiO2 nanofibers by adding aluminum isopropoxide to a common sol-gel
precursor solution utilized to create TiO2 nanofibers. The introduction of
aluminum cations impedes the phase transformation of electrospun TiO2 nanofibers
from the anatase to the rutile phase, which inevitably occurs in the typical
annealing process utilized for the formation of TiO2 crystals. As a result, high
temperature stable anatase TiO2 nanofibers were created in which the crystal
structure was well-maintained even at high annealing temperatures of up to 700
degrees C. Finally, the resulting anatase TiO2 nanofibers were utilized to
prepare LIB anodes, and their electrochemical performance was compared to
pristine TiO2 nanofibers that contain both anatase and rutile phases. Compared to
the electrode prepared with pristine TiO2 nanofibers, the electrode prepared with
anatase TiO2 nanofibers exhibited excellent electrochemical performances such as
an initial Coulombic efficiency of 83.9%, a capacity retention of 89.5% after 100
cycles, and a rate capability of 48.5% at a current density of 10 C (1 C = 200 mA
g-1).
PMID- 28696655
TI - Li1.2Ni0.13Co0.13Mn0.54O2 with Controllable Morphology and Size for High
Performance Lithium-Ion Batteries.
AB - The controllable morphology and size Li-rich Mn-based layered oxide
Li1.2Ni0.13Co0.13Mn0.54O2 with micro/nano structure is successfully prepared
through a simple coprecipitation route followed by subsequent annealing treatment
process. By rationally regulating and controlling the volume ratio of ethylene
glycol (EG) in hydroalcoholic solution, the morphology and size of the final
products can be reasonably designed and tailored from rod-like to olive-like, and
further evolved into shuttle-like with the assistance of surfactant. Further, the
structures and electrochemical properties of the Li-rich layered oxide with
various morphology and size are systematically investigated. The galvanostatic
testing demonstrates that the electrochemical performances of lithium ion
batteries (LIBs) are highly dependent on the morphology and size of
Li1.2Ni0.13Co0.13Mn0.54O2 cathode materials. In particular, the olive-like
morphology cathode material with suitable size exhibits much better
electrochemical performances compared with the other two cathode materials in
terms of initial reversible capacity (297.0 mAh g-1) and cycle performance (95.4%
capacity retention after 100 cycles at 0.5 C), as well as rate capacity (142.8
mAh g-1 at 10 C). The excellent electrochemical performances of the as-prepared
materials could be related to the synergistic effect of well-regulated morphology
and appropriate size as well as their micro/nano structure.
PMID- 28696656
TI - Distinct Chemical and Physical Properties of Janus Nanosheets.
AB - Janus particles have recently garnered significant attention for their distinct
properties compared to particles that are homogeneously functionalized. Moreover,
high aspect ratio Janus particles that are rod-like or planar (i.e., nanosheets)
are especially intriguing considering their interfacial properties as well as
their ability to assemble into higher order and hybrid structures. To date, major
challenges facing the exploration and utilization of 2D Janus particles are
scalability of synthesis, characterization of tailored chemical
functionalization, and ability to introduce a diverse set of functionalities.
Herein, a facile method to access Janus 2D graphene oxide (GO) nanosheets by
combining a Pickering-type emulsion and grafting-from polymerization via ATRP is
reported. Janus GO nanosheets bearing PMMA on one face as well as the
symmetrically functionalized analogue are prepared, and the chemical, thermal,
structural, surface, and interfacial properties of these materials are
characterized. Time-of-flight secondary ion mass spectrometry coupled with
Langmuir-Blodgett films is shown to be an ideal route to conclusively establish
asymmetric functionalization of 2D materials. This work not only provides a
facile route for the preparation of Janus nanosheets but also demonstrates the
direct visualization of polymer grown from the surface of GO.
PMID- 28696657
TI - 3D Structural Model of High-Performance Non-Fullerene Polymer Solar Cells as
Revealed by High-Resolution AFM.
AB - Rapid improvements in nonfullerene polymer solar cells (PSCs) have brought power
conversion efficiencies to greater than 12%. To further improve device
performance, a fundamental understanding of the correlations between structure
and performance is essential. In this paper, based on a typical high-performance
system consisting of J61(one donor-acceptor (D-A) copolymer of benzodithiophene
and fluorine substituted benzotriazole) and ITIC (3,9-bis(2-methylene-(3-(1,1
dicyanomethylene)-indanone)-5,5,11,11-tetrakis(4-hexylphenyl)-dithieno[2,3
d:2',3'-d']-s-indaceno[1,2-b:5,6-b']-dithiophene), a 3D structural model is
directly imaged by employing high-resolution atomic force microscopy (AFM).
Hierarchical morphologies ranging from fiberlike crystallites, several nanometers
in size, to a bicontinuous morphology, having domains tens of nanometers in size,
are observed. A fibrillar interpenetrating networks of J61-rich domains embedded
in a matrix comprised of a J61/ITIC is seen, reflecting the partial miscibility
of J61 with ITIC. These hierarchical nanostructural characteristics are coupled
to significantly enhanced exciton dissociation, and further contribute to
photocurrent and final device performance.
PMID- 28696658
TI - Ultrasensitive Wearable Soft Strain Sensors of Conductive, Self-healing, and
Elastic Hydrogels with Synergistic "Soft and Hard" Hybrid Networks.
AB - Robust, stretchable, and strain-sensitive hydrogels have recently attracted
immense research interest because of their potential application in wearable
strain sensors. The integration of the synergistic characteristics of decent
mechanical properties, reliable self-healing capability, and high sensing
sensitivity for fabricating conductive, elastic, self-healing, and strain
sensitive hydrogels is still a great challenge. Inspired by the mechanically
excellent and self-healing biological soft tissues with hierarchical network
structures, herein, functional network hydrogels are fabricated by the
interconnection between a "soft" homogeneous polymer network and a "hard" dynamic
ferric (Fe3+) cross-linked cellulose nanocrystals (CNCs-Fe3+) network. Under
stress, the dynamic CNCs-Fe3+ coordination bonds act as sacrificial bonds to
efficiently dissipate energy, while the homogeneous polymer network leads to a
smooth stress-transfer, which enables the hydrogels to achieve unusual mechanical
properties, such as excellent mechanical strength, robust toughness, and
stretchability, as well as good self-recovery property. The hydrogels demonstrate
autonomously self-healing capability in only 5 min without the need of any
stimuli or healing agents, ascribing to the reorganization of CNCs and Fe3+ via
ionic coordination. Furthermore, the resulted hydrogels display tunable
electromechanical behavior with sensitive, stable, and repeatable variations in
resistance upon mechanical deformations. Based on the tunable electromechanical
behavior, the hydrogels can act as a wearable strain sensor to monitor finger
joint motions, breathing, and even the slight blood pulse. This strategy of
building synergistic "soft and hard" structures is successful to integrate the
decent mechanical properties, reliable self-healing capability, and high sensing
sensitivity together for assembling a high-performance, flexible, and wearable
strain sensor.
PMID- 28696659
TI - Carbon Nanotube Matrix for Highly Sensitive Biosensors To Detect Pancreatic
Cancer Biomarker CA19-9.
AB - Biosensors fabricated with nanomaterials promise faster, cheaper, and more
efficient alternatives to traditional, often bulky devices for early cancer
diagnosis. In this study, we fabricated a thin film sensing unit on
interdigitated gold electrodes combining polyethyleneimine and carbon nanotubes
in a layer by layer fashion, onto which antibodies anti-CA19-9 were adsorbed with
a supporting layer of N-hydroxysuccinimide and 1-ethyl-3-(3
dimethylaminopropyl)carbodiimide solution. By use of impedance spectroscopy, the
pancreatic cancer biomarker CA19-9 was detected in a buffer with limit of
detection of 0.35 U/mL. This high sensitivity allowed for distinction between
samples of blood serum from patients with distinct probabilities to develop
pancreatic cancer. The selectivity of the biosensor was confirmed in subsidiary
experiments with HT-29 and SW-620 cell lines and possible interferents, e.g., p53
protein, ascorbic acid, and glucose, where significant changes in capacitance
could only be measured with HT-29 that contained the CA19-9 biomarker.
Chemisorption of CA19-9 molecules onto the layer of anti-CA19-9 antibodies was
the mechanism responsible for sensing while electrostatic interactions drove the
adsorption of carbon nanotubes, according to polarization-modulated infrared
reflection absorption spectroscopy (PM-IRRAS). The adsorption behavior was
successfully described by the Langmuir-Freundlich isotherm.
PMID- 28696660
TI - Transient Nanoscopic Phase Separation in Biological Lipid Membranes Resolved by
Planar Plasmonic Antennas.
AB - Nanoscale membrane assemblies of sphingolipids, cholesterol, and certain
proteins, also known as lipid rafts, play a crucial role in facilitating a broad
range of important cell functions. Whereas on living cell membranes lipid rafts
have been postulated to have nanoscopic dimensions and to be highly transient,
the existence of a similar type of dynamic nanodomains in multicomponent lipid
bilayers has been questioned. Here, we perform fluorescence correlation
spectroscopy on planar plasmonic antenna arrays with different nanogap sizes to
assess the dynamic nanoscale organization of mimetic biological membranes. Our
approach takes advantage of the highly enhanced and confined excitation light
provided by the nanoantennas together with their outstanding planarity to
investigate membrane regions as small as 10 nm in size with microsecond time
resolution. Our diffusion data are consistent with the coexistence of transient
nanoscopic domains in both the liquid-ordered and the liquid-disordered
microscopic phases of multicomponent lipid bilayers. These nanodomains have
characteristic residence times between 30 and 150 MUs and sizes around 10 nm, as
inferred from the diffusion data. Thus, although microscale phase separation
occurs on mimetic membranes, nanoscopic domains also coexist, suggesting that
these transient assemblies might be similar to those occurring in living cells,
which in the absence of raft-stabilizing proteins are poised to be short-lived.
Importantly, our work underscores the high potential of photonic nanoantennas to
interrogate the nanoscale heterogeneity of native biological membranes with
ultrahigh spatiotemporal resolution.
PMID- 28696661
TI - Multicolor Super-resolution Fluorescence Microscopy with Blue and Carmine Small
Photoblinking Polymer Dots.
AB - Advances in the development of small photoblinking semiconducting polymer dots
(Pdots) have attracted great interest for use in super-resolution microscopy.
However, multicolor super-resolution imaging using conventional small
photoblinking Pdots remains a challenge due to their limited color choice, broad
emission spectrum, and heavy spectrum crosstalk. Here, we introduce two types of
small photoblinking Pdots with different colors and relatively narrow emission
spectra: blue PFO Pdots and carmine PFTBT5 Pdots for blinking-based statistical
nanoscopy. Both of these probes feature ultrahigh single-particle brightness,
very strong photostability, superior biocompatibility, and robust fluorescence
fluctuation. In addition, these small photoblinking Pdots serve as excellent
labels for dual-color super-resolution optical fluctuation imaging (SOFI) of
specific subcellular structures, indicating their promise for long-term
multicolor SOFI nanoscopy with high spatiotemporal resolution.
PMID- 28696662
TI - Edge Delamination of Monolayer Transition Metal Dichalcogenides.
AB - Delamination of thin films from the supportive substrates is a critical issue
within the thin film industry. The emergent two-dimensional, atomic layered
materials, including transition metal dichalcogenides, are highly flexible; thus
buckles and wrinkles can be easily generated and play vital roles in the
corresponding physical properties. Here we introduce one kind of patterned
buckling behavior caused by the delamination from a substrate initiated at the
edges of the chemical vapor deposition synthesized monolayer transition metal
dichalcogenides, led by thermal expansion mismatch. The atomic force microscopy
and optical characterizations clearly showed the puckered structures associated
with the strain, whereas the transmission electron microscopy revealed the
special sawtooth-shaped edges, which break the geometrical symmetry for the
buckling behavior of hexagonal samples. The condition of the edge delamination is
in accordance with the fracture behavior of thin film interfaces. This edge
delamination and buckling process is universal for most ultrathin two-dimensional
materials, which requires more attention in various future applications.
PMID- 28696663
TI - Chiral Optical Properties of Tapered Semiconductor Nanoscrolls.
AB - Large surface-to-volume ratio, one-dimensional quantum confinement, and strong
optical activity make chiral nanoscrolls ideal for the detection and sensing of
small chiral molecules. Here, we present a simple physical model of chiroptical
phenomena in multilayered tapered semiconductor nanoscrolls. Our model is based
on a linear transformation of coordinates, which converts nanoscrolls into flat
but topologically distorted nanoplatelets whose optical properties can then be
treated analytically. As an illustrative application example, we analyze
absorption and circular dichroism spectra of CdSe nanoscrolls using an eight-band
model of CdSe. We show that the optical activity of the nanoscrolls originates
from the chiral distortion of their crystal lattice and determine selection rules
for the optically active interband transitions. The results of our study may
prove useful for the modeling and design of semiconductor nanoscrolls and
nanoscroll-based materials.
PMID- 28696664
TI - Evaluation of Silver Zeolites Sorbents Toward Their Ability to Promote Stable
CH3I Storage as AgI Precipitates.
AB - In this study, up to 13 different silver zeolites sorbents were prepared by
repeated ion exchange from their parent structures (FAU X and Y, MOR, *BEA, MFI,
FER), characterized, and evaluated for their ability to capture methyl iodide in
the context of a nuclear severe accident. A novel methodology was implemented to
establish structure-activity relationships between sorbent properties and iodine
trapping stability. After saturation of the zeolite bed with CH3I during a
dynamic breakthrough experiment at 100 degrees C, a two-step quantitative
desorption method was elaborated with the aim to quantify separately the CH3I
fractions trapped by physisorption, chemisorption, or reacted as AgI
precipitates. Besides, an analysis of the mechanisms involved in CH3I sorption
and decomposition processes was also carried out. Overall, Ag/Y zeolites
displayed the highest fractions trapped as stable AgI precipitates, thanks to the
presence of high amounts of dispersed silver species at accessible locations in
the large supercages, and their low sodium content.
PMID- 28696665
TI - Tuning Plasmon Resonance in Magnetoplasmonic Nanochains by Controlling
Polarization and Interparticle Distance for Simple Preparation of Optical
Filters.
AB - Magnetoplasmonic Fe3O4-coated Ag nanoparticles (NPs) are assembled in large scale
(18 * 18 mm2) in order to observe unique modulation of plasmonic coupling and
optical tunable application via both external magnetic field and the combination
of magnetic dipole and electrostatic interactions of particle-particle and
particle-substrate. These large nanochains film exhibits outstanding tunability
of plasmonic resonance from visible to near-infrared range by controlling the
polarization angle and interparticle distance (IPD). The enormous spectral shift
mainly originated from far-field rather than near-field coupling of Ag cores
because of the sufficiently large separation between them in which Fe3O4 shell
acts as spacer. This tunable magnetoplasmonic film can be applicable in the field
of anisotropic optical waveguides, tunable optical filter, and nanoscale sensing
platform.
PMID- 28696666
TI - Amplified Micromagnetic Field Gradients Enable High-Resolution Profiling of Rare
Cell Subpopulations.
AB - Analyzing small collections of cells is challenging because of the need for
extremely high levels of sensitivity. We recently reported a new approach, termed
magnetic ranking cytometry (MagRC), to profile nanoparticle-labeled cells. Using
antibody-functionalized magnetic nanoparticles, we label cells so that each
cell's magnetization is proportional to its surface expression of a selected
biomarker. Using a microfluidic device that sorts the cells into 100 different
zones based on magnetic labeling levels, we generate profiles that report on the
level and distribution of surface expression in small collections of cells. Here,
we present a new set of studies investigating in depth parameters such as flow
rate and magnetic nanoparticle size that affect device performance using both
experiments and modeling. We present a model that further elucidates the
mechanism of cell capture and use it to optimize device performance to
efficiently capture rare cells. We show that this method has excellent
specificity and can be used to characterize rare cells even in the presence of
whole blood.
PMID- 28696667
TI - Levitated Plasmonic Nanoantennas in an Aqueous Environment.
AB - We report on the manipulation of a plasmonic nanoantenna in an aqueous solution
using an electrostatic trap created between a glass nanopipette and a substrate.
By scanning a trapped gold nanosphere in the near field of a single colloidal
quantum dot embedded under the substrate surface, we demonstrate about 8-fold
fluorescence enhancement over a lateral full width at half-maximum of about 45
nm. We analyze our results with the predictions of numerical electromagnetic
simulations under consideration of the electrostatic free energy in the trap. Our
approach could find applications in a number of experiments, where plasmonic
effects are employed at liquid-solid interfaces.
PMID- 28696668
TI - Dual-Mode Mass Spectrometric Imaging for Determination of in Vivo Stability of
Nanoparticle Monolayers.
AB - Effective correlation of the in vitro and in vivo stability of nanoparticle-based
platforms is a key challenge in their translation into the clinic. Here, we
describe a dual imaging method that site-specifically reports the stability of
monolayer-functionalized nanoparticles in vivo. This approach uses laser ablation
inductively coupled plasma mass spectrometry (LA-ICP-MS) imaging to monitor the
distributions of the nanoparticle core material and laser desorption/ionization
mass spectrometry (LDI-MS) imaging to report on the monolayers on the
nanoparticles. Quantitative comparison of the images reveals nanoparticle
stability at the organ and suborgan level. The stability of particles observed in
the spleen was location-dependent and qualitatively similar to in vitro studies.
In contrast, in vivo stability of the nanoparticles in the liver differed
dramatically from in vitro studies, demonstrating the importance of in vivo
assessment of nanoparticle stability.
PMID- 28696669
TI - In Vitro Reconstitution of OxyA Enzymatic Activity Clarifies Late Steps in
Vancomycin Biosynthesis.
AB - Studies on the biosynthesis of glycopeptide antibiotics have provided many
insights into the strategies that Nature employs to build architecturally
strained molecules. A key structural feature of vancomycin, the founding member
of this class, is a set of three aromatic cross-links that are introduced via yet
unknown mechanisms. Previous reports have identified three cytochrome P450
enzymes involved in this process and demonstrated enzymatic activity for OxyB,
which installs the first aromatic cross-link. However, the activities of the
remaining two P450 enzymes have not been recapitulated. Herein, we show that OxyA
generates the second bis-aryl ether bond in vancomycin and that it exhibits
strict substrate specificity toward the chlorinated, OxyB-cross-linked product.
No OxyA product is detected with the unchlorinated substrate. Together with
previous results, these data suggest that chlorination occurs after OxyB- but
before OxyA-catalyzed cross-link formation. Our results have important
implications for the chemo-enzymatic synthesis of vancomycin and its analogs.
PMID- 28696670
TI - Highly Efficient Photocatalyst Based on a CdS Quantum Dots/ZnO Nanosheets 0D/2D
Heterojunction for Hydrogen Evolution from Water Splitting.
AB - A novel CdS/ZnO heterojunction constructed of zero-dimensional (0D) CdS quantum
dots (QDs) and two-dimensional (2D) ZnO nanosheets (NSs) was rationally designed
for the first time. The 2D ZnO NSs were assembled into ZnO microflowers (MFs) via
an ultrasonic-assisted hydrothermal procedure (100 degrees C, 12 h) in the
presence of a NaOH solution (0.06 M), and CdS QDs were deposited on both sides of
every ZnO NS in situ by using the successive ionic-layer absorption and reaction
method. It was found that the ultrasonic treatment played an important role in
the generation of ZnO NSs, while NaOH was responsible to the assembly of a flower
like structure. The obtained CdS/ZnO 0D/2D heterostructures exhibited remarkably
enhanced photocatalytic activity for hydrogen evolution from water splitting in
comparison with other CdS/ZnO heterostructures with different dimensional
combinations such as 2D/2D, 0D/three-dimensional (3D), and 3D/0D. Among them,
CdS/ZnO-12 (12 deposition cycles of CdS QDs) exhibited the highest hydrogen
evolution rate of 22.12 mmol/g/h, which was 13 and 138 times higher than those of
single CdS (1.68 mmol/g/h) and ZnO (0.16 mmol/g/h), respectively. The enhanced
photocatalytic activity can be attributed to several positive factors, such as
the formation of a Z-scheme photocatalytic system, the tiny size effect of 0D CdS
QDs and 2D ZnO NSs, and the intimate contact between CdS QDs and ZnO NSs. The
formation of a Z-scheme photocatalytic system remarkably promoted the separation
and migration of photogenerated electron-hole pairs. The tiny size effect
effectively decreased the recombination probability of electrons and holes. The
intimate contact between the two semiconductors efficiently reduced the migration
resistance of photogenerated carriers. Furthermore, CdS/ZnO-12 also presented
excellent stability for photocatalytic hydrogen evolution without any decay
within five cycles in 25 h.
PMID- 28696671
TI - Simultaneous Delivery of Multiple Antibacterial Agents from Additively
Manufactured Porous Biomaterials to Fully Eradicate Planktonic and Adherent
Staphylococcus aureus.
AB - Implant-associated infections are notoriously difficult to treat and may even
result in amputation and death. The first few days after surgery are the most
critical time to prevent those infections, preferably through full eradication of
the micro-organisms entering the body perioperatively. That is particularly
important for patients with a compromised immune system such as orthopedic
oncology patients, as they are at higher risk for infection and complications.
Full eradication of bacteria is, especially in a biofilm, extremely challenging
due to the toxicity barrier that prevents delivery of high doses of antibacterial
agents. This study aimed to use the potential synergistic effects of multiple
antibacterial agents to prevent the use of toxic levels of these agents and
achieve full eradication of planktonic and adherent bacteria. Silver ions and
vancomycin were therefore simultaneously delivered from additively manufactured
highly porous titanium implants with an extremely high surface area incorporating
a bactericidal coating made from chitosan and gelatin applied by electrophoretic
deposition (EPD). The presence of the chitosan/gelatin (Ch+Gel) coating, Ag, and
vancomycin (Vanco) was confirmed by X-ray photoelectron spectroscopy (XPS) and
Fourier transform infrared spectroscopy (FTIR). The release of vancomycin and
silver ions continued for at least 21 days as measured by inductively coupled
plasma (ICP) and UV-spectroscopy. Antibacterial behavior against Staphylococcus
aureus, both planktonic and in biofilm, was evaluated for up to 21 days. The
Ch+Gel coating showed some bactericidal behavior on its own, while the loaded
hydrogels (Ch+Gel+Ag and Ch+Gel+Vanco) achieved full eradication of both
planktonic and adherent bacteria without causing significant levels of toxicity.
Combining silver and vancomycin improved the release profiles of both agents and
revealed a synergistic behavior that further increased the bactericidal effects.
PMID- 28696672
TI - Magnetic Extraction of Acinetobacter baumannii Using Colistin-Functionalized
gamma-Fe2O3/Au Core/Shell Composite Nanoclusters.
AB - Acinetobacter baumannii is a Gram-negative bacterium of increasing concern due to
its virulence and persistence in combat and healthcare environments. The
incidence of both community-acquired and nosocomial A. baumannii infections is on
the rise in foreign and domestic healthcare facilities. Treatment options are
limited due to the acquisition of multidrug resistance to the few effective
antibiotics. Currently, the most effective pharmaceutically based treatment for
multidrug-resistant A. baumannii infections is the antibiotic colistin (polymyxin
E). To minimize side effects associated with administration of colistin or other
toxic antimicrobial agents, we propose the development of a nanotechnology
mediated treatment strategy. In this design-based effort, colistin-functionalized
multilayered, inorganic, magnetoplasmonic nanoconstructs were fabricated to bind
to the surface of A. baumannii. This result, for the first time, demonstrates a
robust, pharmaceutical-based motif for high affinity, composite nanoparticulates
targeting the A. baumannii surface. The antibiotic-activated nanomaterials
demonstrated cytocompatibility with human cells and no acute bacterial toxicity
at nanoparticle to bacterial concentrations <10 000:1. The magnetomotive
characteristics of the nanomaterial enabled magnetic extraction of the bacteria.
In a macroscale environment, maximal separation efficiencies exceeding 38% were
achieved. This result demonstrates the potential for implementation of this
technology into micro- or mesofluidic-based separation environments to enhance
extraction efficiencies. The future development of such a mesofluidic-based,
nanotechnology-mediated platform is potentially suitable for adjuvant therapies
to assist in the treatment of sepsis.
PMID- 28696673
TI - How Nothing Boosts Affinity: Hydrophobic Ligand Binding to the Virtually Vacated
S1' Pocket of Thermolysin.
AB - We investigated the hydration state of the deep, well-accessible hydrophobic S1'
specificity pocket of the metalloprotease thermolysin with purposefully designed
ligands using high-resolution crystallography and isothermal titration
calorimetry. The S1' pocket is known to recognize selectively a very stringent
set of aliphatic side chains such as valine, leucine, and isoleucine of putative
substrates. We engineered a weak-binding ligand covering the active site of the
protease without addressing the S1' pocket, thus transforming it into an enclosed
cavity. Its sustained accessibility could be proved by accommodating noble gas
atoms into the pocket in the crystalline state. The topology and electron content
of the enclosed pocket with a volume of 141 A3 were analyzed using an
experimental MAD-phased electron density map that was calibrated to an absolute
electron number scale, enabling access to the total electron content within the
cavity. Our analysis indicates that the S1' pocket is virtually vacated, thus
free of any water molecules. The thermodynamic signature of the reduction of the
void within the pocket by growing aliphatic P1' substituents (H, Me, iPr, iBu)
reveals a dramatic, enthalpy-dominated gain in free energy of binding resulting
in a factor of 41 000 in Kd for the H-to-iBu transformation. Substituents placing
polar decoy groups into the pocket to capture putatively present water molecules
could not collect any evidence for a bound solvent molecule.
PMID- 28696674
TI - Lasso Peptide Benenodin-1 Is a Thermally Actuated [1]Rotaxane Switch.
AB - Mechanically interlocked molecules that change their conformation in response to
stimuli have been developed by synthetic chemists as building blocks for
molecular machines. Here we describe a natural product, the lasso peptide
benenodin-1, which exhibits conformational switching between two distinct
threaded conformers upon actuation by heat. We have determined the structures of
both conformers and have characterized the kinetics and energetics of the
conformational switch. Single amino acid substitutions to benenodin-1 generate
peptides that are biased to a single conformer, showing that the switching
behavior is potentially an evolvable trait in these peptides. Lasso peptides such
as benenodin-1 can be recognized and cleaved by enzymes called lasso peptide
isopeptidases. We show that only the native conformer of benenodin-1 is cleaved
by its cognate isopeptidase. Thus, thermally induced conformational switching of
benenodin-1 may also be relevant to the biological function of these molecules.
PMID- 28696675
TI - Fundamentally Addressing Bromine Storage through Reversible Solid-State
Confinement in Porous Carbon Electrodes: Design of a High-Performance Dual-Redox
Electrochemical Capacitor.
AB - Research in electric double-layer capacitors (EDLCs) and rechargeable batteries
is converging to target systems that have battery-level energy density and
capacitor-level cycling stability and power density. This research direction has
been facilitated by the use of redox-active electrolytes that add faradaic charge
storage to increase energy density of the EDLCs. Aqueous redox-enhanced
electrochemical capacitors (redox ECs) have, however, performed poorly due to
cross-diffusion of soluble redox couples, reduced cycle life, and low operating
voltages. In this manuscript, we propose that these challenges can be
simultaneously met by mechanistically designing a liquid-to-solid phase
transition of oxidized catholyte (or reduced anolyte) with confinement in the
pores of electrodes. Here we demonstrate the realization of this approach with
the use of bromide catholyte and tetrabutylammonium cation that induces
reversible solid-state complexation of Br2/Br3-. This mechanism solves the
inherent cross-diffusion issue of redox ECs and has the added benefit of greatly
stabilizing the reactive bromine generated during charging. Based on this new
mechanistic insight on the utilization of solid-state bromine storage in redox
ECs, we developed a dual-redox EC consisting of a bromide catholyte and an ethyl
viologen anolyte with the addition of tetrabutylammonium bromide. In comparison
to aqueous and organic electric double-layer capacitors, this system enhances
energy by factors of ca. 11 and 3.5, respectively, with a specific energy of ~64
W.h/kg at 1 A/g, a maximum power density >3 kW/kg, and cycling stability over
7000 cycles.
PMID- 28696676
TI - Alternative Affinity Ligands for Immunoglobulins.
AB - The demand for recombinant therapeutic antibodies and Fc-fusion proteins is
expected to increase in the years to come. Hence, extensive efforts are
concentrated on improving the downstream processing. In particular, the
development of better-affinity chromatography matrices, supporting robust time-
and cost-effective antibody purification, is warranted. With the advances in
molecular design and high-throughput screening approaches from chemical and
biological combinatorial libraries, novel affinity ligands representing
alternatives to bacterial immunoglobulin (Ig)-binding proteins have entered the
scene. Here, we review the design, development, and properties of diverse classes
of alternative antibody-binding ligands, ranging from engineered versions of Ig
binding proteins, to artificial binding proteins, peptides, aptamers, and
synthetic small-molecular-weight compounds. We also provide examples of
applications for the novel affinity matrices in chromatography and beyond.
PMID- 28696677
TI - Monolithic Peptide-Nucleic Acid Hybrid Functioning as an Artificial
Microperoxidase.
AB - A new peptide nucleic acid (PNA) with an installed peroxidase function has been
developed. Fmoc solid phase peptide synthesis prepared a PNA hybrid (VQKCAQCHTVE
(C2H4O)2CH2-[PNA(T)]6-G) that renders the microperoxidase backbone, followed by
reconstitution with hemin. The resulting holocompound catalyzed the oxidation of
3,3',5,5'-tetramthylbenzidine by H2O2 to 50% that of natural microperoxidase-11,
whereas the apo-form and hemin gave no responses. The peroxidase domain was found
to be active toward direct electrochemistry and the PNA hybrid served for gene
sensor; in the presence of the target DNA (5'-CATGTATAAAAAA-3'), an electrode
attached DNA probe (5'-TsTsTsTsTsTCTCATACATG-3') showed the ferric-to-ferrous
quasi-reversible wave (-276 mV vs Ag/AgCl) through sandwich hybridization.
Moreover, the hybridization product could accept H2O2 as an oxidant to enhance
the reduction current, which occurred likely based on the iron(II)-center
recycling with specific rate constant of 0.19 s-1.
PMID- 28696678
TI - Benchmarking Water Quality from Wastewater to Drinking Waters Using Reduced
Transcriptome of Human Cells.
AB - One of the major challenges in environmental science is monitoring and assessing
the risk of complex environmental mixtures. In vitro bioassays with limited key
toxicological end points have been shown to be suitable to evaluate mixtures of
organic pollutants in wastewater and recycled water. Omics approaches such as
transcriptomics can monitor biological effects at the genome scale. However, few
studies have applied omics approach in the assessment of mixtures of organic
micropollutants. Here, an omics approach was developed for profiling bioactivity
of 10 water samples ranging from wastewater to drinking water in human cells by a
reduced human transcriptome (RHT) approach and dose-response modeling.
Transcriptional expression of 1200 selected genes were measured by an Ampliseq
technology in two cell lines, HepG2 and MCF7, that were exposed to eight serial
dilutions of each sample. Concentration-effect models were used to identify
differentially expressed genes (DEGs) and to calculate effect concentrations
(ECs) of DEGs, which could be ranked to investigate low dose response.
Furthermore, molecular pathways disrupted by different samples were evaluated by
Gene Ontology (GO) enrichment analysis. The ability of RHT for representing
bioactivity utilizing both HepG2 and MCF7 was shown to be comparable to the
results of previous in vitro bioassays. Finally, the relative potencies of the
mixtures indicated by RHT analysis were consistent with the chemical profiles of
the samples. RHT analysis with human cells provides an efficient and cost
effective approach to benchmarking mixture of micropollutants and may offer novel
insight into the assessment of mixture toxicity in water.
PMID- 28696679
TI - Divergent Rhodium-Catalyzed Cyclization Reactions of Enoldiazoacetamides with
Nitrosoarenes.
AB - The first cyclization reactions of enoldiazo compounds with nitrosoarenes have
been developed. Under the catalysis of rhodium(II) octanoate, [3 + 2]-cyclization
between enoldiazoacetamides and nitrosoarenes occurred through cleavages of the
enol double bond and the amide bond, thus furnishing fully substituted 5
isoxazolone derivatives. Upon changing the catalyst to rhodium(II)
caprolactamate, the reaction pathway switched to an unprecedented formal [5 + 1]
cyclization that provided multifunctionalized 1,3-oxazin-4-ones with near
exclusivity under otherwise identical conditions. Mechanistic studies uncovered
distinct catalytic activities and reaction intermediates, which plausibly
rationalized the novel reactivity and catalyst-controlled chemodivergence.
Furthermore, a mechanism-inspired enantioselective rhodium-catalyzed reaction of
gamma-substituted enoldiazoacetamide with nitrosobenzene produced highly
enantioenriched heterocycle-linked trialkylamine.
PMID- 28696680
TI - Emergent Properties of an Organic Semiconductor Driven by its Molecular
Chirality.
AB - Chiral molecules exist as pairs of nonsuperimposable mirror images; a fundamental
symmetry property vastly underexplored in organic electronic devices. Here, we
show that organic field-effect transistors (OFETs) made from the helically chiral
molecule 1-aza[6]helicene can display up to an 80-fold difference in hole
mobility, together with differences in thin-film photophysics and morphology,
solely depending on whether a single handedness or a 1:1 mixture of left- and
right-handed molecules is employed under analogous fabrication conditions. As the
molecular properties of either mirror image isomer are identical, these changes
must be a result of the different bulk packing induced by chiral composition.
Such underlying structures are investigated using crystal structure prediction, a
computational methodology rarely applied to molecular materials, and linked to
the difference in charge transport. These results illustrate that chirality may
be used as a key tuning parameter in future device applications.
PMID- 28696681
TI - Optical pH Sensor Covering the Range from pH 0-14 Compatible with Mobile-Device
Readout and Based on a Set of Rationally Designed Indicator Dyes.
AB - In this work, a family of pH-responsive fluorescent probes has been designed in a
rational manner with the aid of quantum chemistry tools, covering the entire pH
range from 0-14. Relying on the boron-dipyrromethene (BODIPY) core, all the
probes as well as selected reference dyes display very similar spectroscopic
properties with ON-OFF fluorescence switching responses, facilitating optical
readout in simple devices used for detection and analysis. Embedding of the
probes and reference dyes into hydrogel spots on a plastic strip yielded a test
strip that reversibly indicates pH with a considerably small uncertainty of ~0.1
pH units. These strips are not only reusable but, combined with a 3D-printed case
that can be attached to a smartphone, the USB port of which drives the integrated
LED used for excitation, allows for autonomous operation in on-site or in-the
field applications; the developed Android application software ("app") further
simplifies operation for unskilled users.
PMID- 28696682
TI - Homogeneous Assays of Second Messenger Signaling and Hormone Secretion Using
Thermofluorimetric Methods That Minimize Calibration Burden.
AB - Homogeneous assays are characterized by rapidity, low cost, and simple workflows.
However, relatively few specialized homogeneous platforms have garnered
significant use in biological studies. Inconsistencies in matrix interferences,
limited multiplexability, and the requirement for specialized instrumentation are
among the various reasons for delayed acceptance. Recently, we have shown that
DNA-driven protein assays using thermofluorimetric analysis (TFA) can limit
matrix interference and promote multiplexing, all while requiring only a standard
qPCR instrument for readout. Here, we show that homogeneous, one step (mix-and
read) TFA methods can be extended to the analysis of both a small molecule second
messenger, cyclic adenosine monophosphate (cAMP), and a downstream cell-secreted
hormone, insulin. Differential thermal analysis of DNA melting in these assays
allowed analytical discrimination of background and signal without physical
separation. The direct-readout, differential nature of TFA also promoted assay
consistency and minimized calibration burden; analyte response curves were shown
to be highly repeatable for up to 7 months. TFA protocols were validated by
homogeneous quantification of both cAMP and insulin from single pancreatic islets
undergoing a variety of treatments (glucose, KCl, glucose-responsive
insulinotropic peptide (GIP), forskolin) that act upon glucose transporters,
potassium and calcium channels, and G-protein-coupled receptors to modulate
exocytosis. The results of this study suggest that TFA should be applicable to
homogeneous quantification of a variety of small molecule messengers and protein
analytes with standard instrumentation, thereby simplifying workflows in studies
of cell-signaling cascades.
PMID- 28696683
TI - Standard-Free Bioanalytical Approach for Absolute Quantitation of Drug
Metabolites Utilizing Biosynthesis of Reciprocal Radio and Stable Isotopologues
and Its Application.
AB - The following work describes a combined enzymatic and bioanalytical method that
permits absolute quantitation of metabolites in biological samples without the
requirement for reference metabolite standards. This technique was exemplified
using a radio (14C) isotopologue and a stable (13C6) isotopologue of
acetaminophen as substrates for in vitro biosynthesis of the corresponding radio
and stable isotope labeled metabolites, namely, 14C- and 13C6-glucuronides and
sulfates. By supplanting the use of authentic metabolite standards, traditionally
used to calibrate 13C6-metabolites via liquid chromatography-tandem mass
spectrometry (LC-MS/MS), 13C6-metabolites were radiocalibrated by their 14C
isotopologues via liquid chromatography coupled with radioactivity detection and
mass spectrometry (LC-RAD/MS). The radiocalibrated 13C6-isotopologues were in
turn used to quantitate acetaminophen and its corresponding metabolites in rat
plasma samples by LC-MS/MS. Variation between this and a conventional LC-MS/MS
method using authentic standards for calibration was within +/-17%, permitting
its use in preclinical and clinical applications. Since authentic metabolite
standards are not required under the concept of radio and stable isotopologues
using adapted LC-RAD/MS protocols, significantly fewer resources are required to
support accurate metabolite quantitation which in turn enables efficient analysis
of simple and complex metabolite profiles.
PMID- 28696684
TI - Development of beta-Carotene-Loaded Organogel-Based Nanoemulsion with Improved In
Vitro and In Vivo Bioaccessibility.
AB - beta-Carotene (BC), a naturally occurring lipophilic carotenoid, is beneficial
for human health. However, its water solubility and bioavailability are low. In
this study, organogel-based nanoemulsion was successfully prepared to improve the
loading amount, solubility, and bioavailability of BC. Corn oil was selected as
the oil phase for the organogel as a result of the greatest release amount of BC.
Tween 20 was optimized as the emulsifier based on the highest extent of lipolysis
and BC bioaccessibility. The nanoemulsion was a better alternative than the
organogel according to both the extent of lipolysis and BC bioaccessibility.
Cellular uptake of BC was significantly improved through organogel-based
nanoemulsion compared to BC suspension. Caveolae-/lipid-raft-mediated route was
the main endocytosis pathway. Pharmacokinetic results confirmed that the in vivo
bioavailability of BC in nanoemulsion was 11.5-fold higher than that of BC oil.
The information obtained suggested that organogel-based nanoemulsion may be an
effective encapsulation system for delivery of insoluble and indigestible
bioactive compounds.
PMID- 28696685
TI - Modeling Sequence-Dependent Peptide Fluctuations in Immunologic Recognition.
AB - In cellular immunity, T cells recognize peptide antigens bound and presented by
major histocompatibility complex (MHC) proteins. The motions of peptides bound to
MHC proteins play a significant role in determining immunogenicity. However,
existing approaches for investigating peptide/MHC motional dynamics are
challenging or of low throughput, hindering the development of algorithms for
predicting immunogenicity from large databases, such as those of tumor or
genetically unstable viral genomes. We addressed this by performing extensive
molecular dynamics simulations on a large structural database of peptides bound
to the most commonly expressed human class-I MHC protein, HLA-A*0201. The
simulations reproduced experimental indicators of motion and were used to
generate simple models for predicting site-specific, rapid motions of bound
peptides through differences in their sequence and chemical composition alone.
The models can easily be applied on their own or incorporated into immunogenicity
prediction algorithms. Beyond their predictive power, the models provide insight
into how amino acid substitutions can influence peptide and protein motions and
how dynamic information is communicated across peptides. They also indicate a
link between peptide rigidity and hydrophobicity, two features known to be
important in influencing cellular immune responses.
PMID- 28696686
TI - Free Energy Coupling between DNA Bending and Base Flipping.
AB - Free energy simulations are presented to probe the energetic coupling between DNA
bending and the flipping of a central thymine in double stranded DNA 13mers. The
energetics are shown to depend on the neighboring base pairs, and upstream C or T
or downstream C tended to make flipping more costly. Flipping to the major groove
side was generally preferred. Bending aids flipping, by pushing the system up in
free energy, but for small and intermediate bending angles the two were
uncorrelated. At higher bending angles, bending and flipping became correlated,
and bending primed the system for base flipping toward the major groove. Flipping
of the 6-4 pyrimidine-pyrimidone and pyrimidine dimer photoproducts is shown to
be more facile than for undamaged DNA. For the damages, major groove flipping was
preferred, and DNA bending was much facilitated in the 6-4 pyrimidine-pyrimidone
damaged system. Aspects of the calculations were verified by structural analyses
of protein-DNA complexes with flipped bases.
PMID- 28696687
TI - Probing Dative and Dihydrogen Bonding in Ammonia Borane with Electronic Structure
Computations and Raman under Nitrogen Spectroscopy.
AB - Although ammonia borane is isoelectronic with ethane and they have similar
structures, BH3NH3 exhibits rather atypical bonding compared to that in CH3CH3.
The central bond in ammonia borane is actually a coordinate covalent or dative
bond rather than the conventional covalent C-C bond in ethane where each atom
donates one electron. In addition, strong intermolecular dihydrogen bonds can
form between two or more ammonia borane molecules compared to the relatively weak
dispersion forces between ethane molecules. As a result, ammonia borane's
physical properties are very sensitive to the environment. For example, gas-phase
and solid-state ammonia borane have very different BN bond lengths and BN
stretching frequencies, which led to much debate in the literature. It has been
demonstrated that the use of cluster models based on experimental crystal
structures led to better agreement between theory and experiment. Here, we employ
a variety of cluster models to track how the interaction energies, bond lengths,
and vibrational normal modes evolve with the size and structural characteristics
of the clusters. The M06-2X/6-311++G(2df,2pd) level of theory was selected for
this analysis on the basis of favorable comparison with CCSD(T)/aug-cc-pVTZ data
for the ammonia borane monomer and dimer. Fourteen unique fully optimized
molecular cluster geometries, (BH3NH3)n<=12, and nine crystal models,
(BH3NH3)n<=19, were used to elucidate how the local environment impacts ammonia
borane's physical properties. Computational results for the BN stretching
frequencies are also compared directly to the Raman spectrum of solid ammonia
borane at 77 K using Raman under liquid nitrogen spectroscopy (RUNS). A strong
linear correlation was found to exist between the BN bond length and stretching
frequency, from an isolated monomer to the most distorted BH3NH3 unit in a
cluster or crystal structure model. Excellent agreement was seen between the
frequencies computed for the largest crystal model and the RUNS experimental
spectra (typically within a few wavenumbers).
PMID- 28696688
TI - Convolutional Embedding of Attributed Molecular Graphs for Physical Property
Prediction.
AB - The task of learning an expressive molecular representation is central to
developing quantitative structure-activity and property relationships.
Traditional approaches rely on group additivity rules, empirical measurements or
parameters, or generation of thousands of descriptors. In this paper, we employ a
convolutional neural network for this embedding task by treating molecules as
undirected graphs with attributed nodes and edges. Simple atom and bond
attributes are used to construct atom-specific feature vectors that take into
account the local chemical environment using different neighborhood radii. By
working directly with the full molecular graph, there is a greater opportunity
for models to identify important features relevant to a prediction task. Unlike
other graph-based approaches, our atom featurization preserves molecule-level
spatial information that significantly enhances model performance. Our models
learn to identify important features of atom clusters for the prediction of
aqueous solubility, octanol solubility, melting point, and toxicity. Extensions
and limitations of this strategy are discussed.
PMID- 28696689
TI - Correction to BET Bromodomain Inhibitors with One-Step Synthesis Discovered from
Virtual Screen.
PMID- 28696690
TI - A Kinome-Wide Selective Radiolabeled TrkB/C Inhibitor for in Vitro and in Vivo
Neuroimaging: Synthesis, Preclinical Evaluation, and First-in-Human.
AB - The proto-oncogenes NTRK1/2/3 encode the tropomyosin receptor kinases TrkA/B/C
which play pivotal roles in neurobiology and cancer. We describe herein the
discovery of [11C]-(R)-3 ([11C]-(R)-IPMICF16), a first-in-class positron emission
tomography (PET) TrkB/C-targeting radiolabeled kinase inhibitor lead. Relying on
extensive human kinome vetting, we show that (R)-3 is the most potent and most
selective TrkB/C inhibitor characterized to date. It is demonstrated that [11C]
(R)-3 readily crosses the blood-brain barrier (BBB) in rodents and selectively
binds to TrkB/C receptors in vivo, as evidenced by entrectinib blocking studies.
Substantial TrkB/C-specific binding in human brain tissue is observed in vitro,
with specific reduction in the hippocampus of Alzheimer's disease (AD) versus
healthy brains. We additionally provide preliminary translational data regarding
the brain disposition of [11C]-(R)-3 in primates including first-in-human
assessment. These results illustrate for the first time the use of a kinome-wide
selective radioactive chemical probe for endogenous kinase PET neuroimaging in
human.
PMID- 28696691
TI - Electronic and Functional Scope of Boronic Acid Derived Salicylidenehydrazone
(BASHY) Complexes as Fluorescent Dyes.
AB - A series of boronic acid derived salicylidenehydrazone (BASHY) complexes was
prepared and photophysically characterized. The dye platform can be modified by
(a) electronic tuning along the cyanine-type axis via modification of the donor
acceptor pair and (b) functional tuning via the boronic acid residue. On the one
hand, approach (a) allows the control of photophysical parameters such as Stokes
shift, emission color, and two-photon-absorption (2PA) cross section. The
resulting dyes show emission light-up behavior in nonpolar media and are
characterized by high fluorescence quantum yields (ca. 0.5-0.7) and brightness
(ca. 35000-40000 M-1 cm-1). Moreover, the 2PA cross sections reach values in the
order of 200-300 GM. On the other hand, the variation of the dye structure
through the boronic acid derived moiety (approach (b)) enables the
functionalization of the BASHY platform for a broad spectrum of potential
applications, ranging from biorelevant contexts to optoelectronic materials.
Importantly, this functionalization is generally electronically orthogonal with
respect to the dye's photophysical properties, which are only determined by the
electronic structure of the cyanine-type backbone (approach (a)). Rare exceptions
to this generalization are the presence of redox-active residues (such a
triphenylamine or pyrene). Finally, the advantageous photophysics is complemented
by a significant photostability.
PMID- 28696692
TI - Evaluating Force Field Performance in Thermodynamic Calculations of Cyclodextrin
Host-Guest Binding: Water Models, Partial Charges, and Host Force Field
Parameters.
AB - Computational prediction of noncovalent binding free energies with methods based
on molecular mechanical force fields has become increasingly routine in drug
discovery projects, where they promise to speed the discovery of small molecule
ligands to bind targeted proteins with high affinity. Because the reliability of
free energy methods still has significant room for improvement, new force fields,
or modifications of existing ones, are regularly introduced with the aim of
improving the accuracy of molecular simulations. However, comparatively little
work has been done to systematically assess how well force fields perform,
particularly in relation to the calculation of binding affinities. Hardware
advances have made these calculations feasible, but comprehensive force field
assessments for protein-ligand sized systems still remain costly. Here, we turn
to cyclodextrin host-guest systems, which feature many hallmarks of protein
ligand binding interactions but are generally much more tractable due to their
small size. We present absolute binding free energy and enthalpy calculations,
using the attach-pull-release (APR) approach, on a set of 43 cyclodextrin-guest
pairs for which experimental ITC data are available. The test set comprises both
alpha- and beta-cyclodextrin hosts binding a series of small organic guests, each
with one of three functional groups: ammonium, alcohol, or carboxylate. Four
water models are considered (TIP3P, TIP4Pew, SPC/E, and OPC), along with two
partial charge assignment procedures (RESP and AM1-BCC) and two cyclodextrin host
force fields. The results suggest a complex set of considerations when choosing a
force field for biomolecular simulations. For example, some force field
combinations clearly outperform others at the binding enthalpy calculations but
not for the binding free energy. Additionally, a force field combination which we
expected to be the worst performer gave the most accurate binding free energies -
but the least accurate binding enthalpies. The results have implications for the
development of improved force fields, and we propose this test set, and potential
future elaborations of it, as a powerful validation suite to evaluate new force
fields and help guide future force field development.
PMID- 28696693
TI - Synthesis and Evaluation of Agelastatin Derivatives as Potent Modulators for
Cancer Invasion and Metastasis.
AB - The synthesis of new agelastatin alkaloid derivatives and their anticancer
evaluation in the context of the breast cancer microenvironment is described. A
variety of N1-alkyl and C5-ether agelastatin derivatives were accessed via
application of our strategy for convergent imidazolone synthesis from a common
thioester along with appropriately substituted urea and alcohol components. These
agelastatin derivatives were evaluated in our three-dimensional coculture assay
for the effects of mammary fibroblasts on associated breast cancer cells. We have
discovered that agelastatin alkaloids are potent modulators for cancer invasion
and metastasis at noncytotoxic doses. Herein, we discuss the increased potency of
(-)-agelastatin E as compared to (-)-agelastatin A in this capacity, in addition
to identification of new agelastatin derivatives with activity that is
statistically equivalent to (-)-agelastatin E. The chemistry described in this
report provides a platform for the rapid synthesis of agelastatin derivatives
with excellent potency (50-100 nM) as modulators for cancer invasion and
metastasis.
PMID- 28696694
TI - Discovery of Potent Small-Molecule Inhibitors of Ubiquitin-Conjugating Enzyme
UbcH5c from alpha-Santonin Derivatives.
AB - As a therapeutic target for antitumor necrosis factor (TNF)-alpha interventions,
UbcH5c is one of the key ubiquitin-conjugating enzymes catalyzing ubiquitination
during TNF-alpha-triggered nuclear factor kappa B (NF-kappaB) activation. In the
present study, three series of analogues were designed and synthesized from alpha
santonin, and their UbcH5c inhibitory activities were screened by Western
blotting and NF-kappaB luciferase assay. Further BIAcore, in-gel fluorescence
imaging, and immunoprecipitation assays demonstrated that compound 6d exhibited
robust and specific inhibition of UbcH5c, exceeding that of the positive compound
1 (IJ-5). Mechanistic investigations revealed that compound 6d preferentially
bound to and inactivated UbcH5c by forming a covalent adduct with its active site
Cys85. Furthermore, compound 6d exhibited potent anti-inflammatory activity
against complete Freund's adjuvant-induced adjuvant arthritis in vivo. These
findings suggest that the novel alpha-santonin-derived UbcH5c inhibitor 6d is a
promising lead compound for the development of new antirheumatoid arthritis (RA)
agent.
PMID- 28696695
TI - Structure-Based Approach To Identify 5-[4-Hydroxyphenyl]pyrrole-2-carbonitrile
Derivatives as Potent and Tissue Selective Androgen Receptor Modulators.
AB - In an effort to find new and safer treatments for osteoporosis and frailty, we
describe a novel series of selective androgen receptor modulators (SARMs). Using
a structure-based approach, we identified compound 7, a potent AR (ARE EC50 =
0.34 nM) and selective (N/C interaction EC50 = 1206 nM) modulator. In vivo data,
an AR LBD X-ray structure of 7, and further insights from modeling studies of
ligand receptor interactions are also presented.
PMID- 28696696
TI - Synthesis of Benzopyridoindolone Derivatives via a One-Pot Copper Catalyzed
Tandem Reaction of 2-Iodobenzamide Derivatives and 2-Iodobenzylcyanides.
AB - An efficient approach for the synthesis of benzo-fused pyridoindolone derivatives
via a one-pot copper catalyzed tandem reaction of 2-iodobenzamides with 2
iodobenzylcyanides has been developed. Using this protocol, benzo-fused
pyridoindolone derivatives are obtained in high yields in a relatively short
period of time under mild reaction conditions. To the best of our knowledge, this
is the first approach where one can synthesize free indole N-H benzo-fused
pyridoindolones. Also, both indole and pyridone cores are constructed during the
course of the reaction. The methodology shows good functional group tolerance and
allows synthesis of thiophene-fused pyridoindolones and fused
indolobenzonaphthyridone derivatives.
PMID- 28696698
TI - Lithium Amide Protected against Hydrolysis by Aggregated Lithium Halides: An MS +
DFT Investigation.
AB - Supported by mass spectrometry experiments, DFT computations indicate that the
lithium amide of a 3-aminopyrrolidine (lithium benzhydryl(1-benzylpyrrolidin-3
yl)amide, 1-Li) is protected, up to a certain limit, against hydrolysis when it
is aggregated with a strongly polar partner such as LiCl, LiBr, or MeLi.
PMID- 28696697
TI - Development of a Potent Inhibitor of the Plasmodium Proteasome with Reduced
Mammalian Toxicity.
AB - Naturally derived chemical compounds are the foundation of much of our
pharmacopeia, especially in antiproliferative and anti-infective drug classes.
Here, we report that a naturally derived molecule called carmaphycin B is a
potent inhibitor against both the asexual and sexual blood stages of malaria
infection. Using a combination of in silico molecular docking and in vitro
directed evolution in a well-characterized drug-sensitive yeast model, we
determined that these compounds target the beta5 subunit of the proteasome. These
studies were validated using in vitro inhibition assays with proteasomes isolated
from Plasmodium falciparum. As carmaphycin B is toxic to mammalian cells, we
synthesized a series of chemical analogs that reduce host cell toxicity while
maintaining blood-stage and gametocytocidal antimalarial activity and proteasome
inhibition. This study describes a promising new class of antimalarial compound
based on the carmaphycin B scaffold, as well as several chemical structural
features that serve to enhance antimalarial specificity.
PMID- 28696699
TI - Effect of Growth Temperature on Tailoring the Size and Aspect Ratio of Gold
Nanorods.
AB - The influence of temperature on the gold nanorod synthesis process and its effect
on tailoring the size and aspect ratio have not been fully investigated and
understood. A comprehensive study, involving SEM and TEM microscopy, Vis-NIR
spectroscopy, quantitative data analysis and theoretical simulation, is performed
to understand the effect of growth temperature on size, aspect ratio, and shape
uniformity of gold nanorods that are synthesized by a recently developed binary
surfactant seed-mediated AuNR synthesis method. It has been demonstrated that the
temperature can be used as a simple processing parameter to viably tailor the
size and aspect ratio of AuNRs as well as the corresponding surface plasmon
resonance behavior. The temperature coefficients for length, diameter, and aspect
ratio have been, respectively, determined to be 3.5 nm/ degrees C, 3.9 nm/
degrees C, and -0.18/ degrees C. With a combination of controlling temperature
and formulation, the binary surfactant seed-mediated AuNR synthesis method
expects to be a convenient way for producing gold nanorods with a large range of
size and aspect ratio suitable for different applications.
PMID- 28696700
TI - Regio- and Diastereoselective Three-Component Reactions via Trapping of Ammonium
Ylides with N-Alkylquinolinium Salts: Synthesis of Multisubstituted Tetra- and
Dihydroquinoline Derivatives.
AB - Pd(II)-catalyzed three-component reactions via trapping of ammonium ylides with N
alkylquinolinium salts are reported. These reactions provided polyfunctional
polycyclic tetrahydroquinolines or 4-substituted 1,4-dihydroquinolines in
excellent yields (89-99% and 89-98%, respectively) with high regioselectivities
and moderate to good diastereoselectivities (up to 95:5 dr) under mild reaction
conditions.
PMID- 28696701
TI - Enhanced Fluorescence of 3,3'-Diformyl BINOL by Functional Secondary Amines.
AB - Although 3,3'-diformylBINOL (S)-1 shows little change in its fluorescence when
treated with primary amines, its fluorescence can be greatly enhanced by using
functional secondary amines including beta- and gamma-amino alcohols and 1,2- and
1,3-bis(secondary amine) compounds. It has been demonstrated that the functional
secondary amines react with (S)-1 to convert the conjugated aldehyde groups to
unconjugated oxazolidines or aminals to turn on the fluorescence.
PMID- 28696702
TI - Highly Conductive Polypropylene-Graphene Nonwoven Composite via Interface
Engineering.
AB - Here we report a highly conductive polypropylene-graphene nonwoven composite via
direct coating of melt blown polypropylene (PP) nonwoven fabrics with graphene
oxide (GO) dispersions in N,N-dimethylformamide (DMF), followed by the chemical
reduction of GO with hydroiodic acid (HI). GO as an amphiphilic macromolecule can
be dispersed in DMF homogeneously at a concentration of 5 mg/mL, which has much
lower surface tension (37.5 mN/m) than that of GO in water (72.9 mN/m, at 5
mg/mL). The hydrophobic PP nonwoven has a surface energy of 30.1 mN/m, close to
the surface tension of GO in DMF. Therefore, the PP nonwoven can be easily wetted
by the GO/DMF dispersion without any pretreatment. Soaking PP nonwoven in a
GO/DMF dispersion leads to uniform coatings of GO on PP-fiber surfaces. After
chemical reduction of GO to graphene, the resulting PP/graphene nonwoven
composite offers an electrical conductivity of 35.6 S m-1 at graphene loading of
5.2 wt %, the highest among the existing conductive PP systems reported,
indicating that surface tension of coating baths has significant impact on the
coating uniformity and affinity. The conductivity of our PP/graphene nonwoven is
also stable against stirring washing test. In addition, here we demonstrate a
monolithic supercapacitor derived from the PP-GO nonwoven composite by using a
direct laser-patterning process. The resulted sandwich supercapacitor shows a
high areal capacitance of 4.18 mF/cm2 in PVA-H2SO4 gel electrolyte. The resulting
highly conductive or capacitive PP/graphene nonwoven carries great promise to be
used as electronic textiles.
PMID- 28696703
TI - Implantation of Fe3O4 Nanoparticles in Shells of Au@m-SiO2 Yolk@Shell
Nanocatalysts with Both Improved Recyclability and Catalytic Activity.
AB - Multifunctional nanocatalysts of Au@Fe3O4/m-SiO2 yolk@shell hybrids had been
developed through a template-assisted synthesis, where Fe3O4 nanoparticles (~12
nm) and m-SiO2 shells were sequentially assembled on surfaces of Au/SiO2
core/shell templates, followed by selective etching of the inner SiO2 cores,
leading to the formation of Au@Fe3O4/m-SiO2 yolk@shell hybrids. The Fe3O4
nanoparticles were implanted in the inner surfaces of m-SiO2 shells with
partially exposed surfaces to the inner cavity. The novel design not only ensures
a high surface area (540.0 m2/g) and saturation magnetization (48.6 emu/g) of the
hybrids but also enables interaction between Au and Fe3O4 nanoparticles.
Catalytic tests toward the reduction of 4-nitrophenol in the presence of NaBH4
indicated that Au@Fe3O4/m-SiO2 yolk@shell nanocatalysts not only showed high
stability and recyclability but also maintained improved catalytic activity as a
result of the synergetic effect resulting from Au and Fe3O4 interactions.
PMID- 28696704
TI - Polymer-Rich Composite Electrolytes for All-Solid-State Li-S Cells.
AB - Polymer-rich composite electrolytes with lithium
bis(fluorosulfonyl)imide/poly(ethylene oxide) (LiFSI/PEO) containing either Li
ion conducting glass ceramic (LICGC) or inorganic Al2O3 fillers are investigated
in all-solid-state Li-S cells. In the presence of the fillers, the ionic
conductivity of the composite polymer electrolytes (CPEs) does not increase
compared to the plain LiFSI/PEO electrolyte at various tested temperatures. The
CPE with Al2O3 fillers improves the stability of the Li/electrolyte interface,
while the Li-S cell with a LICGC-based CPE delivers high sulfur utilization of
1111 mAh g-1 and areal capacity of 1.14 mAh cm-2. In particular, the cell
performance gets further enhanced when combining these two CPEs (Li | Al2O3
CPE/LICGC-CPE | S), reaching a capacity of 518 mAh g-1 and 0.53 mAh cm-2 with
Coulombic efficiency higher than 99% at the end of 50 cycles at 70 degrees C.
This study shows that the CPEs can be promising electrolyte candidates to develop
safe and high-performance all-solid-state Li-S batteries.
PMID- 28696705
TI - Surface Design of Separators for Oil/Water Separation with High Separation
Capacity and Mechanical Stability.
AB - A convection heat treatment that can replace existing chemical oxidation methods
was developed for the preparation of hierarchically oxidized Cu meshes with
various surface morphologies, representing a very simple and green route that
does not involve toxic chemicals. Three types of Cu meshes [bumpy-like (BL) and
short and long needle-like (NL) structures] exhibited similar separation
efficiencies of 95-99% over 20 separation cycles, as indicated by their similar
water contact angles (WCAs; 147-150 degrees ). However, these Cu meshes exhibited
different flux behaviors. Excessively rough and excessively smooth surfaces of
the Cu mesh resulted in increased resistance to flow and to a decrease of the
penetration of oil. A surface with intermediate smoothness, such as the BL-Cu
mesh, was necessary for high flux over a broad range of oil viscosities.
Furthermore, a less rough surface was more suitable for the separation of highly
viscous oil. Computational fluid dynamics (CFD) simulations were carried out to
support our experimental results. The BL-Cu meshes also showed outstanding
mechanical stability because of their low resistance to the flow of fluids.
PMID- 28696706
TI - Large Differences in the Optical Spectrum Associated with the Same Complex: The
Effect of the Anisotropy of the Embedding Lattice.
AB - Transition-metal complexes with a well-defined geometry are usually considered to
display almost the same properties independently of the system where they are
embedded. Here we show that the above statement is not true depending on the
anisotropy of the host lattice, which is revealed in the form of the electric
field created by the rest of lattice ions over the complex. To illustrate this
concept we analyze the origin of the surprisingly large differences in the d-d
optical transitions of two systems containing square-planar CuF42- complexes,
CaCuF4, and center II in Cu2+-doped Ba2ZnF6, even though the Cu2+-F-distance
difference is just found to be 1%. Using a minimalist first-principles model we
show that the different morphology of the host lattices creates an anisotropic
field that red-shifts the in vacuo complex transitions to the 1.25-1.70 eV range
in CaCuF4, while it blue-shifts them to the 1.70-3.0 eV region in Ba2ZnF6:Cu2+.
This particular example shows how the lattice anisotropy strongly alters the
optical properties of a given transition-metal complex. This knowledge opens a
new path to tune the spectra of this large family of systems.
PMID- 28696708
TI - Photocatalytic alpha-Acylation of Ethers.
AB - Direct coupling of ethers and acyl halides was promoted by a binary catalytic
system comprising an Ir-based photocatalyst and a Ni complex under blue-light
irradiation. Photocatalysts with high triplet energy directed the catalysis, and
the reaction likely proceeded by triplet-triplet energy transfer from the excited
photocatalysts. Chlorine radicals generated from an excited Ni complex bearing a
Ni-Cl bond would be responsible for generating alpha-oxy radicals leading to the
alpha-acylated ethers.
PMID- 28696707
TI - Cyclophilin B Deficiency Causes Abnormal Dentin Collagen Matrix.
AB - Cyclophilin B (CypB) is an endoplasmic reticulum-resident protein that regulates
collagen folding, and also contributes to prolyl 3-hydroxylation (P3H) and lysine
(Lys) hydroxylation of collagen. In this study, we characterized dentin type I
collagen in CypB null (KO) mice, a model of recessive osteogenesis imperfecta
type IX, and compared to those of wild-type (WT) and heterozygous (Het) mice.
Mass spectrometric analysis demonstrated that the extent of P3H in KO collagen
was significantly diminished compared to WT/Het. Lys hydroxylation in KO was
significantly diminished at the helical cross-linking sites, alpha1/alpha2(I) Lys
87 and alpha1(I) Lys-930, leading to a significant increase in the under
hydroxylated cross-links and a decrease in fully hydroxylated cross-links. The
extent of glycosylation of hydroxylysine residues was, except alpha1(I) Lys-87,
generally higher in KO than WT/Het. Some of these molecular phenotypes were
distinct from other KO tissues reported previously, indicating the dentin
specific control mechanism through CypB. Histological analysis revealed that the
width of predentin was greater and irregular, and collagen fibrils were sparse
and significantly smaller in KO than WT/Het. These results indicate a critical
role of CypB in dentin matrix formation, suggesting a possible association
between recessive osteogenesis imperfecta and dentin defects that have not been
clinically detected.
PMID- 28696709
TI - Carbon Dots as Nanodispersants for Multiwalled Carbon Nanotubes: Reduced
Cytotoxicity and Metal Nanoparticle Functionalization.
AB - The colloidal stabilization of multiwalled carbon nanotubes (MWCNTs) in an
aqueous medium through noncovalent interactions has potential benefits toward the
practical use of this one-dimensional carbonaceous material for biomedical
applications. Here, we report that fluorescent carbon nanodots can efficiently
function as dispersing agents in the preparation of stable aqueous suspensions of
CNTs at significant concentrations (0.5 mg/mL). The amphiphilic nature of carbon
dots with a hydrophobic graphitic core could effectively interact with the CNT
surface, whereas hydrophilic oxygenated functionalization on the C-dot surface
provided excellent water dispersibility. The resultant CNT-C-dot composite showed
significantly reduced cytotoxicity compared to that of unmodified or protein
coated CNTs, as demonstrated by cell viability and proliferation assays.
Furthermore, the reducing capability of C-dots could be envisaged toward the
formation of a catalytically active metal nanoparticle-CNT-C-dot composite
without the addition of any external reducing or stabilizing agents that showed
excellent catalytic activity toward the reduction of p-nitrophenol in the
presence of NaBH4. Overall, the present work establishes C-dots as an efficient
stabilizer for aqueous dispersions of CNTs, leading to an all-carbon
nanocomposite that can be useful for different practical applications.
PMID- 28696710
TI - Mechanism and Prediction of Gas Permeation through Sub-Nanometer Graphene Pores:
Comparison of Theory and Simulation.
AB - Due to its atomic thickness, porous graphene with sub-nanometer pore sizes
constitutes a promising candidate for gas separation membranes that exhibit
ultrahigh permeances. While graphene pores can greatly facilitate gas mixture
separation, there is currently no validated analytical framework with which one
can predict gas permeation through a given graphene pore. In this work, we
simulate the permeation of adsorptive gases, such as CO2 and CH4, through sub
nanometer graphene pores using molecular dynamics simulations. We show that gas
permeation can typically be decoupled into two steps: (1) adsorption of gas
molecules to the pore mouth and (2) translocation of gas molecules from the pore
mouth on one side of the graphene membrane to the pore mouth on the other side.
We find that the translocation rate coefficient can be expressed using an
Arrhenius-type equation, where the energy barrier and the pre-exponential factor
can be theoretically predicted using the transition state theory for classical
barrier crossing events. We propose a relation between the pre-exponential factor
and the entropy penalty of a gas molecule crossing the pore. Furthermore, on the
basis of the theory, we propose an efficient algorithm to calculate CO2 and CH4
permeances per pore for sub-nanometer graphene pores of any shape. For the
CO2/CH4 mixture, the graphene nanopores exhibit a trade-off between the CO2
permeance and the CO2/CH4 separation factor. This upper bound on a Robeson plot
of selectivity versus permeance for a given pore density is predicted and
described by the theory. Pores with CO2/CH4 separation factors higher than 102
have CO2 permeances per pore lower than 10-22 mol s-1 Pa-1, and pores with
separation factors of ~10 have CO2 permeances per pore between 10-22 and 10-21
mol s-1 Pa-1. Finally, we show that a pore density of 1014 m-2 is required for a
porous graphene membrane to exceed the permeance-selectivity upper bound of
polymeric materials. Moreover, we show that a higher pore density can potentially
further boost the permeation performance of a porous graphene membrane above all
existing membranes. Our findings provide insights into the potential and the
limitations of porous graphene membranes for gas separation and provide an
efficient methodology for screening nanopore configurations and sizes for the
efficient separation of desired gas mixtures.
PMID- 28696711
TI - Cobalt-Catalyzed Cross-Couplings of Bench-Stable Alkynylzinc Pivalates with
(Hetero)Aryl and Alkenyl Halides.
AB - A catalytic system consisting of CoCl2.2LiCl and TMEDA enables the cross-coupling
of various electron-poor aryl and heteroaryl halides with various alkynylzinc
pivalates. Coupling with alkenyl halides proceeds with retention of
configuration.
PMID- 28696712
TI - Bridging Zirconia Nodes within a Metal-Organic Framework via Catalytic Ni-Hydroxo
Clusters to Form Heterobimetallic Nanowires.
AB - Metal-organic frameworks (MOFs), with their well-ordered pore networks and
tunable surface chemistries, offer a versatile platform for preparing well
defined nanostructures wherein functionality such as catalysis can be
incorporated. Notably, atomic layer deposition (ALD) in MOFs has recently emerged
as a versatile approach to functionalize MOF surfaces with a wide variety of
catalytic metal-oxo species. Understanding the structure of newly deposited
species and how they are tethered within the MOF is critical to understanding how
these components couple to govern the active material properties. By combining
local and long-range structure probes, including X-ray absorption spectroscopy,
pair distribution function analysis, and difference envelope density analysis,
with electron microscopy imaging and computational modeling, we resolve the
precise atomic structure of metal-oxo species deposited in the MOF NU-1000
through ALD. These analyses demonstrate that deposition of NiOxHy clusters occurs
selectively within the smallest pores of NU-1000, between the zirconia nodes,
serving to connect these nodes along the c-direction to yield heterobimetallic
metal-oxo nanowires. This bridging motif perturbs the NU-1000 framework
structure, drawing the zirconia nodes closer together, and also underlies the
sintering resistance of these clusters during the hydrogenation of light olefins.
PMID- 28696713
TI - Modulation of the Binding Affinity of Polyzwitterion-Conjugated Protein by Ion
Specific Effects in Crowded Environments.
AB - Macromolecular crowding could influence the binding affinity of the
polyzwitterion-conjugated proteins. Herein, the hydrolysis of N-succinyl-Ala-Ala
Pro-Phe p-nitroanilide by the poly(carboxybetaine) conjugated alpha-chymotrypsin
(PCT) was employed as a model system to investigate the modulation of the binding
affinity of the polyzwitterion-conjugated proteins by the ion-specific effects in
the crowded environments. In comparison with the bare alpha-chymotrypsin (BCT),
the binding affinity of the PCT to the peptide is stronger in the dilute
solutions but becomes weaker in the crowded environments. Our study demonstrates
that the kosmotropic Ac- anion is incapable of achieving a stronger enzymatic
binding affinity of the PCT than the BCT in the highly crowded environments. By
contrast, the binding affinity of the PCT can be enhanced to be stronger than
that of the BCT by the chaotropic SCN- anion in the crowded environments.
PMID- 28696714
TI - A Braided Hetero[2](3)rotaxane.
AB - A novel braided hetero[2](3)rotaxane is demonstrated by integrating the braided
structure and mechanically interlocked rotaxane, in which a heterotritopic linear
tris(dialkylammonium) guest penetrates a heterotritopic tris(crown ether) host,
resulting in the formation of braided pseudohetero[2](3)rotaxane with different
crossing and threading points. Then a braided hetero[2](3)rotaxane is constructed
through the "CuAAC" click reaction.
PMID- 28696715
TI - Approach to the Synthesis of Briarane Diterpenes through a Dianionic Claisen
Rearrangement and Ring-Closing Metathesis.
AB - The synthesis of the briarane-brianthein A core has been accomplished utilizing
an extension of the dianionic Ireland-Claisen rearrangement to establish the C1
quaternary carbon and the adjacent C10 ring juncture stereocenters. Two
sequential ring-closing metathesis reactions were exploited to construct the 6-10
trans fused ring system.
PMID- 28696716
TI - Factors Governing the Diels-Alder Reactivity of (2,7)Pyrenophanes.
AB - The physical factors governing the Diels-Alder reactivity of (2,7)pyrenophanes
have been computationally explored using state-of-the-art Density Functional
Theory calculations. It is found that the [4 + 2]-cycloaddition reactions between
these cyclophanes and tetracyanoethylene, which occur concertedly through highly
asynchronous transition states, proceed with lower activation barriers and are
more exothermic than the analogous process involving the parent planar pyrene.
The influence of the bent equilibrium geometry of the pyrenophane as a function
of the length of the bridge as well as the nature of the tether on the
transformation are analyzed in detail. By means of the Activation Strain Model of
reactivity and the Energy Decomposition Analysis methods, a detailed quantitative
understanding of the reactivity of this particular family of cyclophanes is
presented.
PMID- 28696717
TI - Ligand-Accelerated Gold-Catalyzed Addition of in Situ Generated Hydrazoic Acid to
Alkynes under Neat Conditions.
AB - The direct addition of in situ generated hydrazoic acid to alkynes is realized
without solvent by using a gold catalyst derived from a recently designed
remotely functionalized biaryl-2-ylphosphine ligand (i.e., WangPhos). With
terminal alkynes, the additions are mostly realized with 0.1 mol% catalyst
loadings and at 40 degrees C. With more challenging internal alkynes devoid of
direct EWG substitution, the one-step transformation is realized for the first
time with generally high efficiency at ambient temperature.
PMID- 28696718
TI - Cross-Metathesis Approach to the Tricyclic Marine Alkaloids (-)-Fasicularin and (
)-Lepadiformine A.
AB - A cross-metathesis protocol has been developed to provide facile access to highly
hindered trisubstituted alpha-branched olefins, which when coupled with a
cationic azaspirocyclization reaction, generates the marine alkaloids (-)
fasicularin 2 and a pro-forma synthesis of (-)-lepadiformine A 1.
PMID- 28696719
TI - An Insight into Glyco-Microheterogeneity of Plasma von Willebrand Factor by Mass
Spectrometry.
AB - Human plasma von Willebrand Factor (VWF) plays essential roles in primary
hemostasis in cooperation with other coagulations factors. There is ample
indication that glycosylation affects many biological phases during the protein
life cycle. However, comprehensive characterization of all probable N-glycosites
simultaneous with O-glycosites is still not fully revealed. Thus, the intention
of this exploration was to estimate the occupancy of all canonical N-glycosites
besides simultaneous characterization of N- and O-glycoforms. An RP-LC-MS/MS
system functionalized with CID and HCD tandem mass was utilized to analyze VWF. N
Glycosite occupancy varied along the protein backbone chain. Out of 257 HCD
spectra, 181 characterized glycoforms were specified as either N- or O
glycosites. Sequential cleavage of glycosidic bonds along with Human Database
mass matching have confirmed the glycoform structures. A total of 173 glycoforms
represented most commonly biantennary and infrequently tri- and tetra-antennary N
glycans beside high mannose, hybrid, ABH antigen-terminated, and sulfated N
glycans. Many glycoforms were common across all N-sites. Noteworthy, previously
unreported N-glycosites within domain D'(TIL'-E') showed glycosylation. Moreover,
sialylated core 1 and core 2 O-glycans were detected on 2298T. Given subtle
characterization of site-specific glycoforms, we can attain a profound
understanding of the biological roles of VWF as well as facilitate the production
of VWF-based therapeutics.
PMID- 28696720
TI - Bacterial Production of a Pederin Analogue by a Free-Living Marine
Alphaproteobacterium.
AB - The polyketide pederin family are cytotoxic compounds isolated from insects,
lichen, and marine sponges. During the past decade, different uncultivable
bacteria symbionts have been proposed as the real producers of these compounds,
such as those found in insects, lichen, and marine sponges, and their trans-AT
polyketide synthase gene clusters have been identified. Herein we report the
isolation and biological activities of a new analogue of the pederin family,
compound 1, from the culture of a marine heterotrophic alphaproteobacterium,
Labrenzia sp. PHM005. This is the first report of the production of a pederin
type compound by a free-living marine bacteria that could be cultured in the
laboratory.
PMID- 28696721
TI - An Extraordinarily Stable DNA Minidumbbell.
AB - The minidumbbell (MDB) is a new type of native DNA structure. At neutral pH, two
TTTA or CCTG repeats can fold into the highly compact MDB with a melting
temperature of ~22 degrees C. Owing to the relatively low thermodynamic
stability, MDBs have been proposed to be the structural intermediates that lead
to efficient DNA repair escape and thus repeat expansions. In this study, we
reveal that two CCTG repeats can also form an extraordinarily stable MDB with a
melting temperature of ~46 degrees C at pH 5.0. This unusual stability
predominantly results from the formation of a three hydrogen bond C+.C mispair
between the two minor groove cytosine residues. Due to the drastic stability
change, the CCTG MDB, when combined with its complementary sequence, shows
instant and complete structural conversions when the pH switches between 5.0 and
7.0, making the system serve as a simple and efficient pH-controlled molecular
switch.
PMID- 28696722
TI - Sensitivity of Electron Transfer Mediated Decay to Ion Pairing.
AB - Ion pairing in electrolyte solutions remains a topic of discussion despite a long
history of research. Very recently, nearest-neighbor mediated electronic de
excitation processes of core hole vacancies (electron transfer mediated decay,
ETMD) were proposed to carry a spectral fingerprint of local solvation structure
and in particular of contact ion pairs. Here, for the first time, we apply
electron-electron coincidence detection to a liquid microjet, and record ETMD
spectra of Li 1s vacancies in aqueous solutions of lithium chloride (LiCl) in
direct comparison to lithium acetate (LiOAc). A change in the ETMD spectrum
dependent on the electrolyte anion identity is observed for 4.5 M salt
concentration. We discuss these findings within the framework of the formation
and presence of contact ion pairs and the unique sensitivity of ETMD spectroscopy
to ion pairing.
PMID- 28696723
TI - Optically Activated Delayed Fluorescence.
AB - We harness the photophysics of few-atom silver nanoclusters to create the first
fluorophores capable of optically activated delayed fluorescence (OADF). In
analogy with thermally activated delayed fluorescence, often resulting from
oxygen- or collision-activated reverse intersystem crossing from triplet levels,
this optically controllable/reactivated visible emission occurs with the same 2.2
ns fluorescence lifetime as that produced with primary excitation alone but is
excited with near-infrared light from either of two distinct, long-lived
photopopulated dark states. In addition to faster ground-state recovery under
long-wavelength co-illumination, this "repumped" visible fluorescence occurs many
microsceconds after visible excitation and only when gated by secondary near-IR
excitation of ~1-100 MUs-lived dark excited states. By deciphering the Ag
nanocluster photophysics, we demonstrate that OADF improves upon previous optical
modulation schemes for near-complete background rejection in fluorescence
detection. Likely extensible to other fluorophores with photopopulatable excited
dark states, OADF holds potential for drastically improving fluorescence signal
recovery from high backgrounds.
PMID- 28696724
TI - A New, Short, and Stereocontrolled Synthesis of C2-Symmetric 1,2-Diamines.
AB - The previously unknown 5-spirocyclohexylisoimidazole has been made efficiently
and simply by reaction of ammonia, glyoxal hydrate, and cyclohexanone. It is a
very useful precursor for the diastereocontrolled synthesis of many C2-symmetric
1,2-diamines, a class which is important for the generation of a variety of C2
symmetric reagents and catalysts for enantioselective synthesis.
PMID- 28696725
TI - Ag/Bronsted Acid Co-Catalyzed Spiroketalization of beta-Alkynyl Ketones toward
Spiro[chromane-2,1'-isochromene] Derivatives.
AB - A new Ag/Bronsted acid co-catalyzed spiroketalization of beta-alkynyl ketones
with para-quinone methides (p-QMs) has been established, enabling multiple C-C
and C-O bond-forming events to access densely functionalized spiro[chromane-2,1'
isochromene] derivatives with generally excellent diastereoselectivity and good
yields. A reasonable mechanism for forming these 6,6-dibenzannulated spiroketals
involving 6-endo-dig oxo-cyclization and 1,6-addition-cyclization cascades is
proposed.
PMID- 28696726
TI - Grain Boundary Structures and Collective Dynamics of Inversion Domains in Binary
Two-Dimensional Materials.
AB - Understanding and controlling the properties and dynamics of topological defects
is a lasting challenge in the study of two-dimensional materials, and is crucial
to achieve high-quality films required for technological applications. Here grain
boundary structures, energies, and dynamics of binary two-dimensional materials
are investigated through the development of a phase field crystal model that is
parametrized to match the ordering, symmetry, energy, and length scales of
hexagonal boron nitride. Our studies reveal some new dislocation core structures
for various symmetrically and asymmetrically tilted grain boundaries, in addition
to those obtained in previous experiments and first-principles calculations. We
also identify a defect-mediated growth dynamics for inversion domains governed by
the collective atomic migration and defect core transformation at grain
boundaries and junctions, a process that is related to inversion symmetry
breaking in binary lattice.
PMID- 28696727
TI - Exploratory Lattice QCD Study of the Rare Kaon Decay K^{+}->pi^{+}nunu[over -].
AB - We report a first, complete lattice QCD calculation of the long-distance
contribution to the K^{+}->pi^{+}nunu[over -] decay within the standard model.
This is a second-order weak process involving two four-Fermi operators that is
highly sensitive to new physics and being studied by the NA62 experiment at CERN.
While much of this decay comes from perturbative, short-distance physics, there
is a long-distance part, perhaps as large as the planned experimental error,
which involves nonperturbative phenomena. The calculation presented here, with
unphysical quark masses, demonstrates that this contribution can be computed
using lattice methods by overcoming three technical difficulties: (i) a short
distance divergence that results when the two weak operators approach each other,
(ii) exponentially growing, unphysical terms that appear in Euclidean, second
order perturbation theory, and (iii) potentially large finite-volume effects. A
follow-on calculation with physical quark masses and controlled systematic errors
will be possible with the next generation of computers.
PMID- 28696728
TI - Mode Specific Electronic Friction in Dissociative Chemisorption on Metal
Surfaces: H_{2} on Ag(111).
AB - Electronic friction and the ensuing nonadiabatic energy loss play an important
role in chemical reaction dynamics at metal surfaces. Using molecular dynamics
with electronic friction evaluated on the fly from density functional theory, we
find strong mode dependence and a dominance of nonadiabatic energy loss along the
bond stretch coordinate for scattering and dissociative chemisorption of H_{2} on
the Ag(111) surface. Exemplary trajectories with varying initial conditions
indicate that this mode specificity translates into modulated energy loss during
a dissociative chemisorption event. Despite minor nonadiabatic energy loss of
about 5%, the directionality of friction forces induces dynamical steering that
affects individual reaction outcomes, specifically for low-incidence energies and
vibrationally excited molecules. Mode-specific friction induces enhanced loss of
rovibrational rather than translational energy and will be most visible in its
effect on final energy distributions in molecular scattering experiments.
PMID- 28696729
TI - Comment on "Two-Channel Kondo Physics due to As Vacancies in the Layered Compound
ZrAs_{1.58}Se_{0.39}".
PMID- 28696730
TI - Cichorek et al. Reply.
PMID- 28696731
TI - Dark Matter Search Results from the PICO-60 C_{3}F_{8} Bubble Chamber.
AB - New results are reported from the operation of the PICO-60 dark matter detector,
a bubble chamber filled with 52 kg of C_{3}F_{8} located in the SNOLAB
underground laboratory. As in previous PICO bubble chambers, PICO-60 C_{3}F_{8}
exhibits excellent electron recoil and alpha decay rejection, and the observed
multiple-scattering neutron rate indicates a single-scatter neutron background of
less than one event per month. A blind analysis of an efficiency-corrected 1167
kg day exposure at a 3.3-keV thermodynamic threshold reveals no single-scattering
nuclear recoil candidates, consistent with the predicted background. These
results set the most stringent direct-detection constraint to date on the weakly
interacting massive particle (WIMP)-proton spin-dependent cross section at
3.4*10^{-41} cm^{2} for a 30-GeV c^{-2} WIMP, more than 1 order of magnitude
improvement from previous PICO results.
PMID- 28696732
TI - Studying the Dynamics of Relativistic Laser-Plasma Interaction on Thin Foils by
Means of Fourier-Transform Spectral Interferometry.
AB - We apply Fourier-transform spectral interferometry (FTSI) to study the
interaction of intense laser pulses with ultrathin targets. Ultrathin
submicrometer-thick solid CH targets were shot at the PHELIX laser facility with
an intensity in the mid to upper 10^{19} W/cm^{2} range using an innovative
double-pulse structure. The transmitted pulse structure was analyzed by FTSI and
shows a transition from a relativistic transparency-dominated regime for targets
thinner than 500 nm to a hole-boring-dominated laser-plasma interaction for
thicker targets. The results also confirm that the inevitable preplasma expansion
happening during the rising slope of the pulse, a few picoseconds before the
maximum of the pulse is reached, cannot be neglected and plays a dominant role in
laser-plasma interaction with ultrathin solid targets.
PMID- 28696733
TI - Controlling the Topological Sector of Magnetic Solitons in Exfoliated
Cr_{1/3}NbS_{2} Crystals.
AB - We investigate manifestations of topological order in monoaxial helimagnet
Cr_{1/3}NbS_{2} by performing transport measurements on ultrathin crystals. Upon
sweeping the magnetic field perpendicularly to the helical axis, crystals thicker
than one helix pitch (48 nm) but much thinner than the magnetic domain size (~1
MUm) are found to exhibit sharp and hysteretic resistance jumps. We show that
these phenomena originate from transitions between topological sectors with a
different number of magnetic solitons. This is confirmed by measurements on
crystals thinner than 48 nm-in which the topological sector cannot change-that do
not exhibit any jump or hysteresis. Our results show the ability to
deterministically control the topological sector of finite-size Cr_{1/3}NbS_{2}
and to detect intersector transitions by transport measurements.
PMID- 28696734
TI - Coherent Transfer between Low-Angular-Momentum and Circular Rydberg States.
AB - We realize a coherent transfer between a laser-accessible low-angular-momentum
Rydberg state and the circular Rydberg level with maximal angular momentum. It is
induced by a radio frequency field with a high-purity sigma^{+} polarization
resonant on Stark transitions inside the hydrogenic Rydberg manifold. We observe
over a few microseconds more than 20 coherent Rabi oscillations between the
initial Rydberg state and the circular level. We characterize these many-Rydberg
level oscillations and find them in perfect agreement with a simple model. This
coherent transfer opens the way to hybrid quantum gates bridging the gap between
optical communication and quantum information manipulations with microwave cavity
and circuit quantum electrodynamics.
PMID- 28696735
TI - Spatiotemporal Evolution of Runaway Electron Momentum Distributions in Tokamaks.
AB - Novel spatial, temporal, and energetically resolved measurements of
bremsstrahlung hard-x-ray (HXR) emission from runaway electron (RE) populations
in tokamaks reveal nonmonotonic RE distribution functions whose properties depend
on the interplay of electric field acceleration with collisional and synchrotron
damping. Measurements are consistent with theoretical predictions of momentum
space attractors that accumulate runaway electrons. RE distribution functions are
measured to shift to a higher energy when the synchrotron force is reduced by
decreasing the toroidal magnetic field strength. Increasing the collisional
damping by increasing the electron density (at a fixed magnetic and electric
field) reduces the energy of the nonmonotonic feature and reduces the HXR growth
rate at all energies. Higher-energy HXR growth rates extrapolate to zero at the
expected threshold electric field for RE sustainment, while low-energy REs are
anomalously lost. The compilation of HXR emission from different sight lines into
the plasma yields energy and pitch-angle-resolved RE distributions and
demonstrates increasing pitch-angle and radial gradients with energy.
PMID- 28696736
TI - Effect of Partially Screened Nuclei on Fast-Electron Dynamics.
AB - We analyze the dynamics of fast electrons in plasmas containing partially ionized
impurity atoms, where the screening effect of bound electrons must be included.
We derive analytical expressions for the deflection and slowing-down frequencies,
and show that they are increased significantly compared to the results obtained
with complete screening, already at subrelativistic electron energies.
Furthermore, we show that the modifications to the deflection and slowing down
frequencies are of equal importance in describing the runaway current evolution.
Our results greatly affect fast-electron dynamics and have important
implications, e.g., for the efficacy of mitigation strategies for runaway
electrons in tokamak devices, and energy loss during relativistic breakdown in
atmospheric discharges.
PMID- 28696737
TI - Recoil Inversion in the Photodissociation of Carbonyl Sulfide near 234 nm.
AB - We report the observation of recoil inversion of the CO (v=0, J_{CO}=66) state in
the UV dissociation of lab-frame oriented carbonyl sulfide (OCS). This state is
ejected in the opposite direction with respect to all other (>30) states and in
absence of any OCS rotation, thus resulting in spatial filtering of this
particular high-J rovibrational state. This inversion is caused by resonances
occurring in shallow local minima of the molecular potential, which bring the
sulfur closer to the oxygen than the carbon atom, and is a striking example where
such subtleties severely modify the photofragment trajectories. The resonant
behavior is observed only in the photofragment trajectories and not in their
population, showing that stereodynamic measurements from oriented molecules offer
an indispensable probe for exploring energy landscapes.
PMID- 28696738
TI - Quantum-Dot Single-Photon Sources for Entanglement Enhanced Interferometry.
AB - Multiphoton entangled states such as "N00N states" have attracted a lot of
attention because of their possible application in high-precision, quantum
enhanced phase determination. So far, N00N states have been generated in
spontaneous parametric down-conversion processes and by mixing quantum and
classical light on a beam splitter. Here, in contrast, we demonstrate
superresolving phase measurements based on two-photon N00N states generated by
quantum dot single-photon sources making use of the Hong-Ou-Mandel effect on a
beam splitter. By means of pulsed resonance fluorescence of a charged exciton
state, we achieve, in postselection, a quantum enhanced improvement of the
precision in phase uncertainty, higher than prescribed by the standard quantum
limit. An analytical description of the measurement scheme is provided,
reflecting requirements, capability, and restraints of single-photon emitters in
optical quantum metrology. Our results point toward the realization of a real
world quantum sensor in the near future.
PMID- 28696739
TI - Charge Density Waves and the Hidden Nesting of Purple Bronze K_{0.9}Mo_{6}O_{17}.
AB - We introduce the first multiorbital effective tight-binding model to describe the
effect of electron-electron interactions in this system. Upon fixing all the
effective hopping parameters in the normal state against an ab initio band
structure, and with only the overall scale of the interactions as the sole
adjustable parameter, we find that a self-consistent Hartree-Fock solution
reproduces extremely well the experimental behavior of the charge density wave
(CDW) order parameter in the full range 0Hg and qg->Hq, performed in the
approximation of a small b-quark mass, and the numerical calculation of the
squared one-loop amplitudes for gg->Hgg and qg->Hqg, performed within OpenLoops.
We find that QCD corrections to the interference are large and similar to the QCD
corrections to the top-mediated Higgs production cross section. We also observe a
significant reduction in the mass-renormalization scheme uncertainty once the
next-to-leading order QCD prediction for the interference is employed.
PMID- 28696742
TI - Optimal Quantum Interference Thermoelectric Heat Engine with Edge States.
AB - We show theoretically that a thermoelectric heat engine, operating exclusively
due to quantum-mechanical interference, can reach optimal linear-response
performance. A chiral edge state implementation of a close-to-optimal heat engine
is proposed in an electronic Mach-Zehnder interferometer with a mesoscopic
capacitor coupled to one arm. We demonstrate that the maximum power and
corresponding efficiency can reach 90% and 83%, respectively, of the theoretical
maximum. The proposed heat engine can be realized with existing experimental
techniques and has a performance robust against moderate dephasing.
PMID- 28696743
TI - Extremely Large Magnetoresistance in a Topological Semimetal Candidate Pyrite
PtBi_{2}.
AB - While pyrite-type PtBi_{2} with a face-centered cubic structure has been
predicted to be a three-dimensional (3D) Dirac semimetal, experimental study of
its physical properties remains absent. Here we report the angular-dependent
magnetoresistance measurements of a PtBi_{2} single crystal under high magnetic
fields. We observed extremely large unsaturated magnetoresistance (XMR) up to
(11.2*10^{6})% at T=1.8 K in a magnetic field of 33 T, which is comparable to
the previously reported Dirac materials, such as WTe_{2}, LaSb, and NbP. The
crystals exhibit an ultrahigh mobility and significant Shubnikov-de Hass quantum
oscillations with a nontrivial Berry phase. The analysis of Hall resistivity
indicates that the XMR can be ascribed to the nearly compensated electron and
hole. Our experimental results associated with the ab initio calculations suggest
that pyrite PtBi_{2} is a topological semimetal candidate that might provide a
platform for exploring topological materials with XMR in noble metal alloys.
PMID- 28696744
TI - Erratum: Entanglement by Path Identity [Phys. Rev. Lett. 118, 080401 (2017)].
AB - This corrects the article DOI: 10.1103/PhysRevLett.118.080401.
PMID- 28696745
TI - Exact Results for Quenched Bond Randomness at Criticality.
AB - We introduce an exact replica method for the study of critical systems with
quenched bond randomness in two dimensions. For the q-state Potts model, we show
that a line of renormalization group fixed points interpolates from weak to
strong randomness as q-2 grows from small to large values. This theory exhibits a
q-independent sector, and allows at the same time for a correlation length
exponent which keeps the Ising value and continuously varying magnetization
exponent and effective central charge. These findings appear to solve long
standing numerical and theoretical puzzles, and to illustrate the peculiarities
which may characterize the conformal field theories of random fixed points.
PMID- 28696746
TI - Coherent Plasmon and Phonon-Plasmon Resonances in Carbon Nanotubes.
AB - Carbon nanotubes provide a rare access point into the plasmon physics of one
dimensional electronic systems. By assembling purified nanotubes into uniformly
sized arrays, we show that they support coherent plasmon resonances, that these
plasmons couple to nanotube and substrate phonons, and that the resulting phonon
plasmon resonances have quality factors as high as 10. Because nanotube plasmons
intensely strengthen electromagnetic fields and light-matter interactions, they
provide a compelling platform for surface-enhanced spectroscopy and tunable
optical devices at deep-subwavelength scales.
PMID- 28696747
TI - Device-Independent Tests of Quantum Measurements.
AB - We consider the problem of characterizing the set of input-output correlations
that can be generated by an arbitrarily given quantum measurement. Our main
result is to provide a closed-form, full characterization of such a set for any
qubit measurement, and to discuss its geometrical interpretation. As
applications, we further specify our results to the cases of real and complex
symmetric, informationally complete measurements and mutually unbiased bases of a
qubit, in the presence of isotropic noise. Our results provide the optimal device
independent tests of quantum measurements.
PMID- 28696748
TI - Time Resolved Measurements of the Switching Trajectory of Pt/Co Elements Induced
by Spin-Orbit Torques.
AB - We report the experimental observation of spin-orbit torque induced switching of
perpendicularly magnetized Pt/Co elements in a time resolved stroboscopic
experiment based on high resolution Kerr microscopy. Magnetization dynamics is
induced by injecting subnanosecond current pulses into the bilayer while
simultaneously applying static in-plane magnetic bias fields. Highly reproducible
homogeneous switching on time scales of several tens of nanoseconds is observed.
Our findings can be corroborated using micromagnetic modeling only when including
a fieldlike torque term as well as the Dzyaloshinskii-Moriya interaction mediated
by finite temperature.
PMID- 28696749
TI - Reducing Phonon-Induced Decoherence in Solid-State Single-Photon Sources with
Cavity Quantum Electrodynamics.
AB - Solid-state emitters are excellent candidates for developing integrated sources
of single photons. Yet, phonons degrade the photon indistinguishability both
through pure dephasing of the zero-phonon line and through phonon-assisted
emission. Here, we study theoretically and experimentally the
indistinguishability of photons emitted by a semiconductor quantum dot in a
microcavity as a function of temperature. We show that a large coupling to a high
quality factor cavity can simultaneously reduce the effect of both phonon-induced
sources of decoherence. It first limits the effect of pure dephasing on the zero
phonon line with indistinguishabilities above 97% up to 18 K. Moreover, it
efficiently redirects the phonon sidebands into the zero-phonon line and brings
the indistinguishability of the full emission spectrum from 87% (24%) without
cavity effect to more than 99% (76%) at 0K (20K). We provide guidelines for
optimal cavity designs that further minimize the phonon-induced decoherence.
PMID- 28696750
TI - Unveiling Extreme Anisotropy in Elastic Structured Media.
AB - Periodic structures can be engineered to exhibit unique properties observed at
symmetry points, such as zero group velocity, Dirac cones, and saddle points;
identifying these and the nature of the associated modes from a direct reading of
the dispersion surfaces is not straightforward, especially in three dimensions or
at high frequencies when several dispersion surfaces fold back in the Brillouin
zone. A recently proposed asymptotic high-frequency homogenization theory is
applied to a challenging time-domain experiment with elastic waves in a pinned
metallic plate. The prediction of a narrow high-frequency spectral region where
the effective medium tensor dramatically switches from positive definite to
indefinite is confirmed experimentally; a small frequency shift of the pulse
carrier results in two distinct types of highly anisotropic modes. The underlying
effective equation mirrors this behavior with a change in form from elliptic to
hyperbolic exemplifying the high degree of wave control available and the
importance of a simple and effective predictive model.
PMID- 28696751
TI - Detecting Molecular Rotational Dynamics Complementing the Low-Frequency Terahertz
Vibrations in a Zirconium-Based Metal-Organic Framework.
AB - We show clear experimental evidence of cooperative terahertz (THz) dynamics
observed below 3 THz (~100 cm^{-1}), for a low-symmetry Zr-based metal-organic
framework structure, termed MIL-140A [ZrO(O_{2}C-C_{6}H_{4}-CO_{2})]. Utilizing a
combination of high-resolution inelastic neutron scattering and synchrotron
radiation far-infrared spectroscopy, we measured low-energy vibrations
originating from the hindered rotations of organic linkers, whose energy barriers
and detailed dynamics have been elucidated via ab initio density functional
theory calculations. The complex pore architecture caused by the THz rotations
has been characterized. We discovered an array of soft modes with trampolinelike
motions, which could potentially be the source of anomalous mechanical phenomena
such as negative thermal expansion. Our results demonstrate coordinated shear
dynamics (2.47 THz), a mechanism which we have shown to destabilize the framework
structure, in the exact crystallographic direction of the minimum shear modulus
(G_{min}).
PMID- 28696752
TI - Dispersive Dam-Break Flow of a Photon Fluid.
AB - We investigate the temporal photonic analogue of the dam-break phenomenon for
shallow water by exploiting a fiber optics setup. We clearly observe the decay of
the steplike input (photonic dam) into a pair of oppositely propagating
rarefaction wave and dispersive shock wave. Our results show evidence for a
critical transition of the dispersive shock into a self-cavitating state. The
detailed observation of the cavitating state dynamics allows for a fully
quantitative test of the Whitham modulation theory applied to the universal
defocusing nonlinear Schrodinger equation.
PMID- 28696754
TI - Single-Photon Interference due to Motion in an Atomic Collective Excitation.
AB - We experimentally demonstrate the heralded generation of bichromatic single
photons from an atomic collective spin excitation (CSE). The photon arrival times
display collective quantum beats, a novel interference effect resulting from the
relative motion of atoms in the CSE. A combination of velocity-selective
excitation with strong laser dressing and the addition of a magnetic field allows
for exquisite control of this collective beat phenomenon. The present experiment
uses a diamond scheme with near-IR photons that can be extended to include
telecommunications wavelengths or modified to allow storage and retrieval in an
inverted-Y scheme.
PMID- 28696755
TI - Coherent THz Transient Spin Currents by Spin Pumping.
AB - The generation of short spin current pulses is the basis for fast spintronic
devices. In thin bilayer systems consisting of a nonmagnetic metal and a
ferromagnet, a pure spin current is induced by a precessing magnetization into
the nonmagnetic layer by spin pumping. This effect has been experimentally
demonstrated at ferromagnetic resonance at GHz frequencies. Here, it is
theoretically shown that transient magnetization dynamics efficiently generates
short spin current pulses that exhibit two transient contributions. An effective
coherent spin current generation is found far above the ferromagnetic resonance
up to THz frequencies although dynamic magnetization amplitudes are very small in
this regime. The results provide a concept for coherent THz spin current
generation.
PMID- 28696753
TI - Evolution of the Reactor Antineutrino Flux and Spectrum at Daya Bay.
AB - The Daya Bay experiment has observed correlations between reactor core fuel
evolution and changes in the reactor antineutrino flux and energy spectrum. Four
antineutrino detectors in two experimental halls were used to identify 2.2
million inverse beta decays (IBDs) over 1230 days spanning multiple fuel cycles
for each of six 2.9 GW_{th} reactor cores at the Daya Bay and Ling Ao nuclear
power plants. Using detector data spanning effective ^{239}Pu fission fractions
F_{239} from 0.25 to 0.35, Daya Bay measures an average IBD yield sigma[over
]_{f} of (5.90+/-0.13)*10^{-43} cm^{2}/fission and a fuel-dependent variation in
the IBD yield, dsigma_{f}/dF_{239}, of (-1.86+/-0.18)*10^{-43} cm^{2}/fission.
This observation rejects the hypothesis of a constant antineutrino flux as a
function of the ^{239}Pu fission fraction at 10 standard deviations. The
variation in IBD yield is found to be energy dependent, rejecting the hypothesis
of a constant antineutrino energy spectrum at 5.1 standard deviations. While
measurements of the evolution in the IBD spectrum show general agreement with
predictions from recent reactor models, the measured evolution in total IBD yield
disagrees with recent predictions at 3.1sigma. This discrepancy indicates that an
overall deficit in the measured flux with respect to predictions does not result
from equal fractional deficits from the primary fission isotopes ^{235}U,
^{239}Pu, ^{238}U, and ^{241}Pu. Based on measured IBD yield variations, yields
of (6.17+/-0.17) and (4.27+/-0.26)*10^{-43} cm^{2}/fission have been determined
for the two dominant fission parent isotopes ^{235}U and ^{239}Pu. A 7.8%
discrepancy between the observed and predicted ^{235}U yields suggests that this
isotope may be the primary contributor to the reactor antineutrino anomaly.
PMID- 28696757
TI - Selection Rule for Enhanced Dark Matter Annihilation.
AB - We point out a selection rule for enhancement (suppression) of odd (even) partial
waves of dark matter coannihilation or annihilation using the Sommerfeld effect.
Using this, the usually velocity-suppressed p-wave annihilation can dominate the
annihilation signals in the present Universe. The selection mechanism is a
manifestation of the exchange symmetry of identical incoming particles, and
generic for multistate DM with off-diagonal long-range interactions. As a
consequence, the relic and late-time annihilation rates are parametrically
different and a distinctive phenomenology, with large but strongly velocity
dependent annihilation rates, is predicted.
PMID- 28696758
TI - Local Dynamics in Trained Recurrent Neural Networks.
AB - Learning a task induces connectivity changes in neural circuits, thereby changing
their dynamics. To elucidate task-related neural dynamics, we study trained
recurrent neural networks. We develop a mean field theory for reservoir computing
networks trained to have multiple fixed point attractors. Our main result is that
the dynamics of the network's output in the vicinity of attractors is governed by
a low-order linear ordinary differential equation. The stability of the resulting
equation can be assessed, predicting training success or failure. As a
consequence, networks of rectified linear units and of sigmoidal nonlinearities
are shown to have diametrically different properties when it comes to learning
attractors. Furthermore, a characteristic time constant, which remains finite at
the edge of chaos, offers an explanation of the network's output robustness in
the presence of variability of the internal neural dynamics. Finally, the
proposed theory predicts state-dependent frequency selectivity in the network
response.
PMID- 28696759
TI - Erratum: High-Fidelity Bidirectional Nuclear Qubit Initialization in SiC [Phys.
Rev. Lett. 117, 220503 (2016)].
AB - This corrects the article DOI: 10.1103/PhysRevLett.117.220503.
PMID- 28696760
TI - Erratum: Quantum State Discrimination Using the Minimum Average Number of Copies
[Phys. Rev. Lett. 118, 030502 (2017)].
AB - This corrects the article DOI: 10.1103/PhysRevLett.118.030502.
PMID- 28696761
TI - Parametric Oscillation, Frequency Mixing, and Injection Locking of Strongly
Coupled Nanomechanical Resonator Modes.
AB - We study locking phenomena of two strongly coupled, high quality factor
nanomechanical resonator modes to a common parametric drive at a single drive
frequency in different parametric driving regimes. By controlled dielectric
gradient forces we tune the resonance frequencies of the flexural in-plane and
out-of-plane oscillation of the high stress silicon nitride string through their
mutual avoided crossing. For the case of the strong common parametric drive
signal-idler generation via nondegenerate parametric two-mode oscillation is
observed. Broadband frequency tuning of the very narrow linewidth signal and
idler resonances is demonstrated. When the resonance frequencies of the signal
and idler get closer to each other, partial injection locking, injection pulling,
and complete injection locking to half of the drive frequency occurs depending on
the pump strength. Furthermore, satellite resonances, symmetrically offset from
the signal and idler by their beat note, are observed, which can be attributed to
degenerate four-wave mixing in the highly nonlinear mechanical oscillations.
PMID- 28696762
TI - Composite Dislocations in Smectic Liquid Crystals.
AB - Smectic liquid crystals are characterized by layers that have a preferred uniform
spacing and vanishing curvature in their ground state. Dislocations in smectics
play an important role in phase nucleation, layer reorientation, and dynamics.
Typically modeled as possessing one line singularity, the layer structure of a
dislocation leads to a diverging compression strain as one approaches the defect
center, suggesting a large, elastically determined melted core. However, it has
been observed that for large charge dislocations, the defect breaks up into two
disclinations [C. E. Williams, Philos. Mag. 32, 313 (1975)PHMAA40031
808610.1080/14786437508219956]. Here we investigate the topology of the composite
core. Because the smectic cannot twist, transformations between different
disclination geometries are highly constrained. We demonstrate the geometric
route between them and show that despite enjoying precisely the topological rules
of the three-dimensional nematic, the additional structure of line disclinations
in three-dimensional smectics localizes transitions to higher-order point
singularities.
PMID- 28696763
TI - Renormalization Group Flows of Hamiltonians Using Tensor Networks.
AB - A renormalization group flow of Hamiltonians for two-dimensional classical
partition functions is constructed using tensor networks. Similar to tensor
network renormalization [G. Evenbly and G. Vidal, Phys. Rev. Lett. 115, 180405
(2015)PRLTAO0031-900710.1103/PhysRevLett.115.180405; S. Yang, Z.-C. Gu, and X.-G.
Wen, Phys. Rev. Lett. 118, 110504 (2017)PRLTAO0031
900710.1103/PhysRevLett.118.110504], we obtain approximate fixed point tensor
networks at criticality. Our formalism, however, preserves positivity of the
tensors at every step and hence yields an interpretation in terms of Hamiltonian
flows. We emphasize that the key difference between tensor network approaches and
Kadanoff's spin blocking method can be understood in terms of a change of the
local basis at every decimation step, a property which is crucial to overcome the
area law of mutual information. We derive algebraic relations for fixed point
tensors, calculate critical exponents, and benchmark our method on the Ising
model and the six-vertex model.
PMID- 28696764
TI - Achieving Arbitrary Control over Pairs of Polarization States Using Complex
Birefringent Metamaterials.
AB - We demonstrate that the key to realizing arbitrary control over pairs of
polarization states of light, i.e., transforming an arbitrarily polarized pair of
input states to an arbitrarily polarized pair of output states, is the ability to
generate pairs of states with orthogonal polarizations from nonorthogonal pairs
of initial states. Then, we develop a new class of non-Hermitian metamaterials,
termed complex birefringent metamaterials, which are able to do exactly this.
Such materials could facilitate the detection of small polarization changes in
scattering experiments as well as enable new polarization multiplexing schemes in
communications networks.
PMID- 28696765
TI - Electric Dipole Polarizability of ^{48}Ca and Implications for the Neutron Skin.
AB - The electric dipole strength distribution in ^{48}Ca between 5 and 25 MeV has
been determined at RCNP, Osaka from proton inelastic scattering experiments at
forward angles. Combined with photoabsorption data at higher excitation energy,
this enables the first extraction of the electric dipole polarizability
alpha_{D}(^{48}Ca)=2.07(22) fm^{3}. Remarkably, the dipole response of ^{48}Ca
is found to be very similar to that of ^{40}Ca, consistent with a small neutron
skin in ^{48}Ca. The experimental results are in good agreement with ab initio
calculations based on chiral effective field theory interactions and with state
of-the-art density-functional calculations, implying a neutron skin in ^{48}Ca of
0.14-0.20 fm.
PMID- 28696766
TI - Multispecies Trapped-Ion Node for Quantum Networking.
AB - Trapped atomic ions are a leading platform for quantum information networks, with
long-lived identical qubit memories that can be locally entangled through their
Coulomb interaction and remotely entangled through photonic channels. However,
performing both local and remote operations in a single node of a quantum network
requires extreme isolation between spectator qubit memories and qubits associated
with the photonic interface. We achieve this isolation by cotrapping ^{171}Yb^{+}
and ^{138}Ba^{+} qubits. We further demonstrate the ingredients of a scalable ion
trap network node with two distinct experiments that consist of entangling the
mixed species qubit pair through their collective motion and entangling a
^{138}Ba^{+} qubit with an emitted visible photon.
PMID- 28696767
TI - Landau-Zener Transition in a Continuously Measured Single-Molecule Spin
Transistor.
AB - We monitor the Landau-Zener dynamics of a single-ion magnet inserted into a spin
transistor geometry. For increasing field-sweep rates, the spin reversal
probability shows increasing deviations from that of a closed system. In the low
conductance limit, such deviations are shown to result from a dephasing process.
In particular, the observed behaviors are successfully simulated by means of an
adiabatic master equation, with time averaged dephasing (Lindblad) operators. The
time average is tentatively interpreted in terms of the finite time resolution of
the continuous measurement.
PMID- 28696771
TI - Occurrence of Wounds in Nigerian Horses.
AB - This study investigated the occurrence of wounds in Nigerian horses. The study
population was 1,621 horses sold at the Obollo Afor horse lairage in Enugu State,
Nigeria, during a 6-month period: 3 months of dry season and 3 months of rainy
season (February-April and June-August 2012). A total of 207 horses were
systematically sampled and subjected to a comprehensive physical examination.
Those with wounds were marked, recorded, and clinically examined. Of the 207
horses sampled, 21 (10.1%) had wounds. The body distribution of the wounds was
9.5% head, 9.5% forelimbs, 19.1% hind limbs, 4.8% tail, 14.3% flank, 9.5% loin,
19.1% hip, 9.5% barrel, and 4.8% croup. The occurrence of the wounds was not
significantly associated with sex or season, but the occurrence in adults was
significantly (p < .05) higher than that in the young and aged horses. It was
concluded that the occurrence of wounds is relatively high (10.1%), and mainly
the hind limbs, hip, and flank of adult horses are affected. It was recommended
that horse guardians and handlers should be properly educated on the care of
horses.
PMID- 28696768
TI - Limits on Spin-Dependent WIMP-Nucleon Cross Section Obtained from the Complete
LUX Exposure.
AB - We present experimental constraints on the spin-dependent WIMP-nucleon elastic
cross sections from the total 129.5 kg yr exposure acquired by the Large
Underground Xenon experiment (LUX), operating at the Sanford Underground Research
Facility in Lead, South Dakota (USA). A profile likelihood ratio analysis allows
90% C.L. upper limits to be set on the WIMP-neutron (WIMP-proton) cross section
of sigma_{n}=1.6*10^{-41} cm^{2} (sigma_{p}=5*10^{-40} cm^{2}) at 35 GeV c^{
2}, almost a sixfold improvement over the previous LUX spin-dependent results.
The spin-dependent WIMP-neutron limit is the most sensitive constraint to date.
PMID- 28696772
TI - Enhanced detection of feigned cognitive impairment using per item response time
measurements in the Word Memory Test.
AB - Response time (RT) is a less obvious outcome measure than conventional accuracy
measures used in performance validity tests (PVTs). It is also under less
conscious control and is affected by cognitive processes associated with
deception. Studies that assessed the utility of RT for the detection of feigned
cognitive impairment are however numbered. Moreover, RT variability was not
assessed in a clinically used PVT. In the current study, we assessed the utility
of RT measures for the detection of feigned cognitive impairment in the Word
Memory Test (WMT). Healthy participants (N = 90) were randomly assigned to a
simulation or control condition and their per-item RTs were recorded while they
performed the WMT's immediate recognition (IR) subtest. Simulators had longer
mean RTs and larger RT variance than controls. Combining RT measures and the IR
subtest's accuracy score enabled a highly accurate detection of simulators.
Moreover, the combined scale demonstrated incremental value (though slight) in
predicting group membership beyond the use of the accuracy score as the sole PVT
measure. The findings tentatively point toward the usefulness of RT measures to
enhance the detection of feigned cognitive impairment. Further studies are
needed, however, in order to explore the utility of these measures in clinical
settings.
PMID- 28696773
TI - Rail height effects on safety performance of Midwest Guardrail System.
AB - OBJECTIVE: Guardrail heights play a crucial role in the way that errant vehicles
interact with roadside barriers. Low rail heights increase the propensity of
vehicle rollover and override, whereas excessively tall rails promote underride.
Further, rail mounting heights and post embedment depths may be altered by
variations in roadside terrain. An increased guardrail height may be desirable to
accommodate construction tolerances, soil erosion, frost heave, and future
roadway overlays. This study aimed to investigate and identify a maximum safe
installation height for the Midwest Guardrail System that would be robust and
remain crashworthy before and after pavement overlays. METHODS: A research
investigation was performed to evaluate the safety performance of increased
mounting heights for the standard 787-mm (31-in.)-tall Midwest Guardrail System
(MGS) through crash testing and computer simulation. Two full-scale crash tests
with small passenger cars were performed on the MGS with top-rail mounting
heights of 864 and 914 mm (34 and 36 in.). Test results were then used to
calibrate computer simulation models. RESULTS: In the first test, a small car
impacted the MGS with 864-mm (34-in.) rail height at 102 km/h (63.6 mph) and 25.0
degrees and was successfully redirected. In the second test, another small car
impacted the MGS with a 914-mm (36-in.) rail height at 103 km/h (64.1 mph) and
25.6 degrees and was successful. Both system heights satisfied the Manual for
Assessing Safety Hardware (MASH) Test Level 3 (TL-3) evaluation criteria. Test
results were then used to calibrate computer simulation models. A mounting height
of 36 in. was determined to be the maximum guardrail height that would safely
contain and redirect small car vehicles. Simulations confirmed that taller
guardrail heights (i.e., 37 in.) would likely result in small car underride. In
addition, simulation results indicated that passenger vehicle models were
successfully contained by the 34- and 36-in.-tall MGS installed on approach
slopes as steep as 6:1. CONCLUSIONS: A mounting height of 914 mm (36 in.) was
determined to be the maximum guardrail height that would safely contain and
redirect 1100C vehicles and not allow underride or excessive vehicle snag on
support posts. Recommendations were also provided regarding the safety
performance of the MGS with increased height.
PMID- 28696774
TI - Impacts of Encouraging Dog Walking on Returns of Newly Adopted Dogs to a Shelter.
AB - This study involved examining the ability of a postadoption intervention to
reduce returns of newly adopted dogs to shelters by encouraging physical activity
between adopters and their dogs. Guardians in the intervention group received
emails with dog behavior and human activity advice as well as invitations to join
weekly dog walks. Both the intervention and control groups completed surveys
regarding outdoor activity with their dogs, their dog-walking habits, and
perceptions of their dogs' behaviors. Adopter-dog pairs in the intervention group
were not significantly more active than those in the control group, nor did they
show a reduced incidence of returning their dogs. Guardians in both groups who
reported higher obligation and self-efficacy in their dog walking were more
active regardless of experimental condition; however, obligation, dog-walking
self-efficacy, and perceptions about their dogs' on-leash behaviors did not
predict rates of return to the shelter. These findings add to the understanding
of shelter dog re-relinquishment and the effective utilization of resources
postadoption, and they indicate further research is needed to address the
complexities of this newly forming human-dog relationship.
PMID- 28696775
TI - Dry Powder Inhalers and Humidity: Another Factor to Consider to Ensure Adequate
Lung Delivery.
PMID- 28696776
TI - Delving Deep into the Proteome of Lung Fibrosis Brings Plasma Cells to the
Surface.
PMID- 28696756
TI - Search for the Decays B_{s}^{0}->tau^{+}tau^{-} and B^{0}->tau^{+}tau^{-}.
AB - A search for the rare decays B_{s}^{0}->tau^{+}tau^{-} and B^{0}->tau^{+}tau^{-}
is performed using proton-proton collision data collected with the LHCb detector.
The data sample corresponds to an integrated luminosity of 3 fb^{-1} collected
in 2011 and 2012. The tau leptons are reconstructed through the decay tau^{-}
>pi^{-}pi^{+}pi^{-}nu_{tau}. Assuming no contribution from B^{0}->tau^{+}tau^{-}
decays, an upper limit is set on the branching fraction B(B_{s}^{0}->tau^{+}tau^{
})<6.8*10^{-3} at the 95% confidence level. If instead no contribution from
B_{s}^{0}->tau^{+}tau^{-} decays is assumed, the limit is B(B^{0}->tau^{+}tau^{
})<2.1*10^{-3} at the 95% confidence level. These results correspond to the first
direct limit on B(B_{s}^{0}->tau^{+}tau^{-}) and the world's best limit on
B(B^{0}->tau^{+}tau^{-}).
PMID- 28696777
TI - Therapeutic Uses of Triphala in Ayurvedic Medicine.
AB - AIM: The aim of this article is to review the current literature on the
therapeutic uses and efficacy of Triphala. Herbal remedies are among the most
ancient medicines used in traditional systems of healthcare such as Ayurveda.
Triphala, a well-recognized and highly efficacious polyherbal Ayurvedic medicine
consisting of fruits of the plant species Emblica officinalis (Amalaki),
Terminalia bellerica (Bibhitaki), and Terminalia chebula (Haritaki), is a
cornerstone of gastrointestinal and rejuvenative treatment. METHODS: A search of
the PubMed database was conducted. RESULTS: In addition, numerous additional
therapeutic uses described both in the Ayurvedic medical literature and
anecdotally are being validated scientifically. In addition to laxative action,
Triphala research has found the formula to be potentially effective for several
clinical uses such as appetite stimulation, reduction of hyperacidity,
antioxidant, anti-inflammatory, immunomodulating, antibacterial, antimutagenic,
adaptogenic, hypoglycemic, antineoplastic, chemoprotective, and radioprotective
effects, and prevention of dental caries. Polyphenols in Triphala modulate the
human gut microbiome and thereby promote the growth of beneficial Bifidobacteria
and Lactobacillus while inhibiting the growth of undesirable gut microbes. The
bioactivity of Triphala is elicited by gut microbiota to generate a variety of
anti-inflammatory compounds. CONCLUSIONS: This review summarizes recent data on
pharmacological properties and clinical effects of Triphala while highlighting
areas in need of additional investigation and clinical development.
PMID- 28696778
TI - Delayed Alveolar Epithelialization: A Distinct Pathology in Diffuse Acute Lung
Injury.
PMID- 28696779
TI - The impact of retail beverage service training and social host laws on
adolescents' DUI rates in San Diego County, California.
AB - INTRODUCTION: Driving under the influence (DUI) citations are still a serious
concern among drivers aged 16-20 years and have been shown to be related to
increased risk of fatal and nonfatal crashes. A battery of laws and policies has
been enacted to address this concern. Though numerous studies have evaluated
these policies, there is still a need for comprehensive policy evaluations that
take into account a variety of contextual factors. Previous effort by this
research team examined the impact of 20 minimum legal drinking age-21 laws in the
state of California, as they impacted alcohol-related crash rates among drivers
under 21 years of age while at the same time accounting for alcohol and gas
taxes, unemployment rates, sex distribution among drivers, and sobriety
checkpoints. The current research seeks to expand this evaluation to the county
level (San Diego County). More specifically, we evaluate the impact of measures
subject to county control such as retail beverage service (RBS) laws and social
host (SH) laws, as well as media coverage, city employment, alcohol outlet
density, number of sworn officers, alcohol consumption, and taxation policies, to
determine the most effective point of intervention for communities seeking to
reduce underage DUI citations. METHODS: Annual DUI citation data (2000 to 2013),
RBS and SH policies, and city-wide demographic, economic, and environmental
information were collected and applied to each of the 20 cities in San Diego
County, California. A structural equation model was fit to estimate the relative
contribution of the variables of interest to DUI citation rates. RESULTS: Alcohol
consumption and alcohol outlet density both demonstrated a significant increase
in DUI rates, whereas RBS laws, SH laws, alcohol tax rates, media clusters, gas
tax rates, and unemployment rates demonstrated significant decreases in DUI
rates. CONCLUSIONS: At the county level, although RBS laws, SH laws, and media
efforts were found to contribute to a significant reduction in DUI rates, the
largest significant contributors to reducing DUI rates were alcohol and gas
taxation rates. Policy makers interested in reducing DUI rates among teenagers
should examine these variables within their specific communities and consider
conducting community-specific research to determine the best way to do so. Future
efforts should be made to develop models that represent specific communities who
are interested in reducing DUI rates among drivers aged 16-20 years.
PMID- 28696780
TI - Evaluation of the effectiveness of toe board energy-absorbing material for foot,
ankle, and lower leg injury reduction.
AB - OBJECTIVE: Since 2000, numerous improvements have been made to the National
Association for Stock Car Auto Racing, Incorporated (NASCAR(r)) driver restraint
system, resulting in improved crash protection for motorsports drivers.
Advancements have included seats, head and neck restraints (HNRs), seat belt
restraint systems, driver helmets, and others. These enhancements have increased
protection for drivers from severe crash loading. Extending protection to the
driver's extremities remains challenging. Though the drivers' legs are well
contained for lateral and vertical crashes, they remain largely unrestrained in
frontal and frontal oblique crashes. METHOD: Sled testing was conducted for the
evaluation of an energy-absorbing (EA) toe board material to be used as a
countermeasure for leg and foot injuries. Testing included baseline rigid toe
boards, tests with EA material-covered toe boards, and pretest positioning of the
50th percentile male frontal Hybrid III anthropomorphic test device (ATD) lower
extremities. ATD leg and foot instrumentation included foot acceleration and
tibia forces and moments. RESULTS: The sled test data were evaluated using
established injury criteria for tibial plateau fractures, leg shaft fractures,
and calcaneus, talus, ankle, and midfoot fractures. CONCLUSION: A polyurethane EA
foam was found to be effective in limiting axial tibia force and foot
accelerations when subjected to frontal impacts using the NASCAR motorsport
restraint system.
PMID- 28696781
TI - Early Intervention of Cystic Fibrosis Pulmonary Exacerbations Based on Home
Monitoring. eICE through the Looking Glass.
PMID- 28696782
TI - Development of a Novel, Rapid Multiplex Polymerase Chain Reaction Assay for the
Detection and Differentiation of Salmonella enterica Serovars Enteritidis and
Typhimurium Using Ultra-Fast Convection Polymerase Chain Reaction.
AB - Salmonella enterica serovars Enteritidis and Typhimurium are the most common
causative agents of human nontyphoidal salmonellosis. The rapid detection and
timely treatment of salmonellosis are important to increase the curative ratio
and prevent spreading of the disease. In this study, we developed a rapid
multiplex convection polymerase chain reaction (PCR) method to detect Salmonella
spp. and differentiate Salmonella Enteritidis and Salmonella Typhimurium. We used
the invA gene for Salmonella spp. detection. Salmonella Enteritidis-specific
primers and Salmonella Typhimurium-specific primers were designed using the
insertion element (IE) and spy genes, respectively. The primer set for Salmonella
spp. detection clearly detected both Salmonella Enteritidis and Salmonella
Typhimurium after a 21-min amplification reaction. Serovar-specific primer sets
for Salmonella Enteritidis and Salmonella Typhimurium specifically detected each
target species in a 21-min amplification reaction. We were able to detect
Salmonella spp. at a single copy level in the singleplex mode. The limits of
detection for Salmonella Enteritidis and Salmonella Typhimurium were 30 copies in
both the singleplex and multiplex modes. The PCR run time could be reduced to
10.5 min/15 cycles. The multiplex convection PCR method developed in this study
could detect the Salmonella spp. Salmonella Enteritidis and Salmonella
Typhimurium in artificially contaminated milk with as few as 100 colony-forming
unit/mL after 4-h enrichment. The PCR assay developed in this study provides a
rapid, specific, and sensitive method for the detection of Salmonella spp. and
the differentiation of Salmonella Enteritidis and Salmonella Typhimurium.
PMID- 28696783
TI - Course of Neuropsychiatric Symptoms After Introduction and Removal of
Nonsteroidal Anti-Inflammatory Drugs: A Pediatric Observational Study.
AB - OBJECTIVE: Accumulating evidence suggests that anti-inflammatory interventions
can modulate neuropsychiatric symptoms. Pediatric Acute-onset Neuropsychiatric
Syndrome (PANS) is characterized by an abrupt and dramatic onset of obsessive
compulsive (OC) symptoms and/or severely restrictive food intake and at least two
coinciding, equally debilitating neuropsychiatric symptoms. When associated with
group A Streptococcus, the syndrome is labeled Pediatric Autoimmune
Neuropsychiatric Disorder Associated with Streptococcal infections (PANDAS).
Here, we describe the course of neuropsychiatric symptoms in patients diagnosed
with PANS and PANDAS after introduction or removal of nonsteroidal anti
inflammatory drugs (NSAIDs). STUDY DESIGN: We reviewed the electronic medical
records (EMR) of 218 consecutive patients evaluated in our Stanford PANS Clinic
for patients who met strict PANS or PANDAS research criteria and received NSAIDs
for arthritis, pain, and/or psychiatric symptoms. We describe neuropsychiatric
symptoms that were noted in the EMR before, during, and after NSAIDs were
introduced or removed as the sole change in pharmacologic treatment. RESULTS:
Seventy-seven patients were included in the current study. Of the 52 trials in
which NSAID addition was the sole change in treatment, 16 (31%) coincided with an
improvement in patients' neuropsychiatric symptoms. Of the 57 trials in which
removal of NSAID treatment was the sole change in treatment, 20 (35%) coincided
with escalation in patients' neuropsychiatric symptoms. Thirty patients (39%)
experienced side effects, mainly mild gastrointestinal symptoms, which self
resolved after removal of NSAID, reduction of dose, or change in NSAID.
CONCLUSIONS: Improvement in neuropsychiatric symptoms was evident in roughly one
third of NSAID treatment trials. A randomized clinical trial will be necessary to
confirm whether NSAIDs are successful in reducing neuropsychiatric symptoms in
youth with PANS.
PMID- 28696784
TI - The role of tramadol in pain management in Latin America: a report by the Change
Pain Latin America Advisory Panel.
AB - OBJECTIVE: Change Pain Latin America (CPLA) was created to enhance chronic pain
understanding and develop pain management improving strategies in this region.
During its seventh meeting (August 2016), the main objective was to discuss
tramadol's role in treating pain in Latin America. Furthermore, potential pain
management consequences were considered, if tramadol was to become more
stringently controlled. METHODS: Key topics discussed were: main indications for
prescribing tramadol, its pharmacological characteristics, safety and
tolerability, effects of restrictions on its availability and use, and consequent
impact on pain care quality. RESULTS: The experts agreed that tramadol is used to
treat a wide spectrum of non-oncological pain conditions (e.g. post-surgical,
musculoskeletal, post-traumatic, neuropathic, fibromyalgia), as well as cancer
pain. Its relevance when treating special patient groups (e.g. the elderly) is
recognized. The main reasons for tramadol's high significance as a treatment
option are: its broad efficacy, an inconspicuous safety profile and its
availability, considering that access to strong analgesics - mainly controlled
drugs (classical opioids) - is highly restricted in some countries. The CPLA also
agreed that tramadol is well tolerated, without the safety issues associated with
long-term nonsteroidal anti-inflammatory drug (NSAID) use, with fewer opioid-like
side effects than classical opioids and lower abuse risk. CONCLUSIONS: In Latin
America, tramadol is a valuable and frequently used medication for treating
moderate to severe pain. More stringent regulations would have significant impact
on its availability, especially for outpatients. This could cause regression to
older and frequently inadequate pain management methods, resulting in unnecessary
suffering for many Latin American patients.
PMID- 28696785
TI - Exendin-4, a glucagon-like peptide-1 receptor agonist downregulates hepatic
receptor for advanced glycation end products in non-alcoholic steatohepatitis rat
model.
AB - CONTEXT: Exendin-4, a glucagon-like peptide-1 receptor agonist has been shown to
have curative effects on hepatic steatosis in murine models. OBJECTIVE: The
present study aimed to elucidate the effect of Exendin-4 on hepatic receptor for
advanced glycation end products (RAGE) mRNA expression in non-alcoholic
steatohepatitis (NASH) rat model induced by high-fat diet. METHODS: NASH was
induced by high-fat diet intake, and Exendin-4 was given in two different doses.
After 12 weeks, liver enzyme levels, hepatic triglycerides, antioxidant enzymes
and malondialdehyde (MDA) levels, and mRNA RAGE was detected using RT-PCR.
RESULTS: Exendin-4 in high dose reduced significantly liver enzymes activity,
hepatic triglycerides, MDA levels and hepatic mRNA RAGE expression levels with
significantly higher antioxidant enzymes activity. CONCLUSIONS: Our results give
further insights into the mechanisms underlying the curative role of Exendin-4 in
NASH, suggesting that interference with RAGE may be a useful therapeutic approach
to NASH.
PMID- 28696786
TI - Effect of Early and Prophylactic Nonsteroidal Anti-Inflammatory Drugs on Flare
Duration in Pediatric Acute-Onset Neuropsychiatric Syndrome: An Observational
Study of Patients Followed by an Academic Community-Based Pediatric Acute-Onset
Neuropsychiatric Syndrome Clinic.
AB - INTRODUCTION: Pediatric Acute-onset Neuropsychiatric Syndrome (PANS) is
characterized by the sudden onset of severe obsessive-compulsive symptoms and/or
eating restriction along with at least two coinciding neuropsychiatric symptoms.
When associated with group A Streptococcus, the syndrome is labeled Pediatric
Autoimmune Neuropsychiatric Disorder Associated with Streptococcal infections
(PANDAS). An abnormal immune response to infection and subsequent
neuroinflammation is postulated to play an etiologic role. We evaluated the
impact of nonsteroidal anti-inflammatory drug (NSAID) treatment on flare duration
in PANS/PANDAS. METHODS: Patient inclusion criteria: Patients were included if
they had at least one neuropsychiatric deterioration ("flare") that met strict
PANS/PANDAS research criteria and for which flare duration could be assessed.
Flare inclusion criteria: Any flare that started before October 15, 2016 was
included and followed until the flare resolved or until the end of our data
collection (November 1, 2016). Flare exclusion criteria: Flares were excluded if
they were incompletely resolved, treated with aggressive immunomodulation, or
treated with NSAIDs late (>30 days of flare onset). Ninety-five patients met
study inclusion criteria and collectively experienced 390 flares that met flare
criteria. Data were analyzed using multilevel linear models, adjusting for
demographics, disease, and treatment covariates. RESULTS: NSAID use was
associated with a significantly shorter flare duration. Flares not treated with
NSAIDs had a mean duration of approximately 12.2 weeks (95% CI: 9.3-15.1). Flares
that occurred while the child was on NSAID maintenance therapy were approximately
4 weeks shorter than flares not managed with NSAIDs (95% CI: 1.85-6.24; p <
0.0001). Flares treated with NSAIDs within 30 days of flare onset were
approximately 2.6 weeks shorter than flares not managed with NSAIDs (95% CI: 0.43
4.68; p = 0.02). Flares treated prophylactically and those treated early with
NSAIDs did not differ in duration (p = 0.26). Among the flares that received
NSAID treatment within the first 30 days, earlier intervention was modestly
associated with shorter flare durations (i.e., for each day that NSAID treatment
was delayed, flare duration increased by 0.18 weeks; 95% CI: 0.03-0.33; p =
0.02), though it was not statistically significant after controlling for
covariates (p = 0.06). CONCLUSION: NSAIDs given prophylactically or within 30
days of flare onset may shorten neuropsychiatric symptom duration in patients
with new-onset and relapsing/remitting PANS and PANDAS. A randomized placebo
control clinical trial of NSAIDs in PANS is warranted to formally assess
treatment efficacy.
PMID- 28696787
TI - Reduced Morbidity Motivated Adoption of Infant and Young Child Feeding Practices
after Nutrition Education Intervention in Rural Malawi.
AB - This study assessed caregivers' knowledge and practices and factors that
influence the adoption of improved infant and young child feeding (IYCF)
practices after nutrition education in Kasungu and Mzimba districts among 198
caregivers. Mixed-methods convergent-parallel design, including knowledge tests,
focus group discussions, and in-depth interviews in the intervention areas, was
used to collect quantitative and qualitative data. Data were analyzed using count
regression and content analysis, which showed that knowledge increased among
caregivers after nutrition education. The knowledge about diet diversification
for young children as well as about hygienic practices when preparing food and
during feeding improved in addition. Enhanced health among children motivated
caregivers to apply improved IYCF practices. The study was based on the
caregivers' reports. Long-term effects of exposure to nutrition education are
unknown. However, the nutrition education that focused on the child's health
benefits motivated mothers to adopt improved IYCF practices.
PMID- 28696788
TI - Investigation of Medium Chain Fatty Acid Feed Supplementation for Reducing
Salmonella Typhimurium Colonization in Turkey Poults.
AB - Studies indicate that persistent Salmonella colonization occurs in poultry that
are infected early in life, leading to both food safety and public health
concerns. Development of improved preharvest Salmonella management strategies is
needed to reduce poultry product contamination. The objective of this study was
to evaluate the efficacy of a product containing medium chain fatty acids (MCFA)
for reducing early Salmonella colonization in turkey poults. Day-of-hatch turkeys
were provided a standard starter diet supplemented with MCFA at 0 (negative and
positive controls), 1.5, 3, 4.5, or 6 lbs/ton of feed. Positive control and MCFA
treated birds were also crop-gavaged with 108 colony forming units (CFU) of
bioluminescent Salmonella Typhimurium. Gastrointestinal tissue samples were
collected at 3 days postinoculation for bioluminescence imaging (Meckel's
diverticulum to the cloaca) and selective enumeration (cecal contents).
Quantification of bioluminescence indicated that the 4.5 and 6 lbs/ton MCFA
groups had significantly less colonization than the positive control group (p =
0.0412 and p < 0.0001, respectively). Similarly, significantly lower numbers (1
log10 CFU/g reduction) of Salmonella were observed in the ceca of the 6 lbs/ton
MCFA group compared to the positive control group (p = 0.0153). These findings
indicate that incorporation of MCFA in turkey diets can significantly reduce
early Salmonella colonization. In addition, this study highlights the utility of
bioluminescence imaging as a screening methodology for assessing the efficacy of
treatments that may reduce Salmonella in poultry.
PMID- 28696789
TI - Arthroscopic Knot Removal for Failed Superior Labrum Anterior-Posterior Repair
Secondary to Knot-Induced Pain.
AB - BACKGROUND: Studies on failed superior labrum anterior-posterior (SLAP) repair
are increasing. However, the number of reports on treatment options for failed
SLAP repair remains quite low, and the clinical results vary between different
study groups. PURPOSE: To describe the clinical presentation of failed SLAP
repair due to knot-induced pain and evaluate the efficacy of arthroscopic knot
removal. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: The authors
retrospectively reviewed records of 11 patients (mean age, 24.6 +/- 8.6 years;
range, 17-43 years) with stable, healed SLAP lesions with knot-induced pain after
arthroscopic fixation of unstable type II SLAP lesions. All patients demonstrated
a positive compression-rotation test before knot removal. The mean follow-up
duration after knot removal was 48.0 +/- 37.4 months (range, 24-156 months). The
mean duration between primary fixation and knot removal was 21.2 +/- 14.7 months
(range, 8-56 months). RESULTS: Sharp pain (100%) and clicking (64%) were the most
common symptoms. The knot was positioned on the glenoid side in 5 patients and
the labral side in 6 patients. The knots on the glenoid side had associated
humeral head cartilage damage. The mean University of California at Los Angeles
score significantly improved from 15.2 points to 31.7 points after knot removal (
P = .003) Additionally, the mean Constant score greatly improved from a mean of
56.5 points to 89.8 points ( P = .003). At a mean of 3 weeks after surgery, we
observed dramatic pain relief. Six weeks after surgery, the compression-rotation
test was negative in all patients. CONCLUSION: The most common symptom of knot
induced pain after SLAP repair was persistent sharp pain followed by clicking.
The knot appears to be a cause of pain in failed SLAP repairs, and arthroscopic
knot removal can provide dramatic pain relief and significant improvement of
clinical outcomes.
PMID- 28696790
TI - Competitive inhibition of amino acid transport in human preovulatory ovarian
follicles.
AB - : To date we have yet to examine whether amino acid (AA) transport in human
ovarian follicles is affected by competitive inhibition. In contrast,
transplacental transfer of AAs in late-gestation sheep is characterized by
reciprocal competition. This phenomenon has been described by algebraic equations
of umbilical uptake of AAs based on maternal arterial concentrations. In the
present translational study at a university teaching hospital, we verified
whether these equations apply to the transport of AAs from blood to follicular
fluid (FF) in human preovulatory follicles. For this purpose we used our data on
AA concentrations in blood and FF measured earlier by high-performance liquid
chromatography in specimens from 14 patients undergoing oocyte retrieval for in
vitro fertilization after controlled ovarian stimulation. The main outcome
measure was statistical significance of Spearman correlation coefficients for
measured versus calculated concentrations of 8 AAs: isoleucine, leucine, valine,
phenylalanine, methionine, threonine, lysine, and arginine. Equations for
umbilical uptake provided a highly accurate description of blood-to-FF transport
for 7 AAs with the exception of lysine: R >= 0.899 (p < 0.0001) for the branched
chain AAs, R = 0.829 (p = 0.0003) for threonine, R = 0.754 (p = 0.0019) for
arginine, and R = 0.631 (p = 0.0156) for phenylalanine and methionine. We
conclude that these equations indicate competitive inhibition between the AAs
studied. Our study strongly suggests that many AA transport systems operating in
the placenta should also be active in the cells of the preovulatory follicle.
Future studies on AA fluxes in human ovarian follicles must consider possible
competitive inhibition. ABBREVIATIONS: AA: amino acid; FF: follicular fluid;
HPLC: high-performance liquid chromatography.
PMID- 28696791
TI - The Molecular Mechanisms of Ciprofloxacin Resistance in Clinical Campylobacter
jejuni and Their Genotyping Characteristics in Beijing, China.
AB - We assessed the susceptibility of 182 Campylobacter jejuni isolates from patients
with diarrhea to eight antibiotics and analyzed the molecular mechanisms of
ciprofloxacin resistance as well as the genetic characteristics based on
multilocus sequence typing (MLST). The C257T mutation was found on the quinolone
resistance-determining region (QRDR) of the gyrA gene in all ciprofloxacin
resistant strains. Mutations on the QRDR of the gyrB gene were silent. A total of
74 strains had 7 inverted repeat (IR) (a 16-bp IR on the intergenic region
between cmeR and cmeABC) mutation polymorphisms. Compared with strains without
the IR mutations, strains with the IR mutations had higher resistance rates to
ciprofloxacin (94.6% vs. 83.3%), nalidixic acid (94.6% vs. 83.3%), tetracycline
(98.6% vs. 85.2%), doxycycline (91.9% vs. 71.3%), florfenicol (59.5% vs. 17.6%),
chloramphenicol (25.7% vs. 4.6%), gentamicin (16.2% vs. 3.7%), and multidrug
resistance than those without IR mutations (all p < 0.05). With C257T mutation
alone, 89.9% strains with minimum inhibitory concentration (MIC) values focused
on 16, 32, and 64 MUg/mL, whereas strains with C257T mutation in combination with
the IR mutations had a higher ciprofloxacin resistance level with 88.6% MIC
values focused on 64, 128, and 512 MUg/mL (p < 0.0001). The strains in this study
showed a high genetic variability based on MLST with 117 sequence types (STs), 37
of which were novel. CC-21 was the most common clonal complex (CC) followed by CC
353 and CC-45. No association was found between STs and ciprofloxacin resistance.
In conclusion, the C257T mutation on gyrA was the major mechanism for
ciprofloxacin resistance, and the C257T mutation in combination with the IR
mutations might result in more severe ciprofloxacin resistance to C. jejuni.
PMID- 28696792
TI - Direct-to-Consumer Genetic Testing and Orphan Drug Development.
AB - Since the introduction of the Orphan Drug Act (ODA) in 1983, orphan drug
approvals in the United States have jumped from <100 per decade to over 200 per
year. This growth is widely attributed to the financial incentives the ODA gives
to companies that develop these medicines, and it is likely to continue for a
unique reason: partnerships between pharmaceutical firms and direct-to-consumer
(DTC) genetic testing companies. This emerging trend is the subject of this
article, which begins by considering how rare-disease drugs are regulated and the
rising interest in nonclinical genetic testing. It then outlines how DTC
companies analyze DNA and how their techniques benefit researchers and drug
developers. Then, after an overview of the current partnerships between DTCs and
drug developers, it examines concerns about privacy and cost brought up by these
partnerships. The article concludes by contrasting the enormous positive
potential of DTC-pharma relationships and their concomitant dangers, especially
to consumer privacy and cost to the healthcare system.
PMID- 28696793
TI - Need for hyperlipidemia management policy reform in China: learning from the
global experience.
AB - OBJECTIVE: To evaluate the hyperlipidemia prevention programs and policies in
different countries and highlight the need of reforming the hyperlipidemia
prevention policies in China to lower the growing cardiovascular disease (CVD)
risk. RESEARCH DESIGN AND METHODS: PubMed, Google Scholar and Cochrane were
searched for global hyperlipidemia prevention policies. Government-funded
policies pertaining to lipid management were considered for this review. Only
those studies that evaluated the success of prevention policies on the basis of:
(i) achievement of hyperlipidemia targets; (ii) improvement in Cardiovascular
(CV) risk reduction; and (iii) outcomes with reduction in hyperlipidemia after
implementation of the policy, were included. RESULTS: Several global policies and
programs aimed to improve CV health by highlighting lipid profile management.
Implementation of the global and national policies led to improvement in
cholesterol related outcomes such as availability of diagnostic measures,
awareness of the risk factors, decrease in cholesterol levels, achieving healthy
lifestyle to prevent CVD and improvement in availability of hypolipidemic
medications, etc. Statins have been covered under reimbursement policies in many
countries to improve usage and thereby preventing incidence of stroke and CVD. We
observed a need for introducing new programs in China as the ongoing
hyperlipidemia management policies are inadequate. The World Bank Report 2016
recommended that prevention policies in China be modeled on the US Million Hearts
program. CONCLUSIONS: New hyperlipidemia prevention policies must set a time
bound target, and need to be patient and clinician centric in terms of
applications, and revised periodically for long-term benefits.
PMID- 28696794
TI - The effects of asthma medications on reactive oxygen species production in human
monocytes.
AB - OBJECTIVE: Asthma is a chronic inflammatory airway disease induced by many
environmental factors. The inhalation of allergens and pollutants promotes the
production of reactive oxygen species (ROS) leading to airway inflammation, hyper
responsiveness, and remodeling in allergic asthma. The effects of asthma
medications on ROS production are unclear. The present study investigated the
anti-ROS effects of current asthma medications including inhaled corticosteroid
(ICS; budesonide and fluticasone), leukotriene receptor antagonist (LTRA;
montelukast), long-acting beta2 agonists (LABAs; salmeterol and formoterol), and
a new extra-LABA (indacaterol). METHODS: The human monocyte cell line THP-1 cells
were pre-treated with different concentrations of the asthma medications at
different time points after hydrogen peroxide (H2O2) stimulation. H2O2 production
was measured with DCFH-DA by flow cytometry. RESULTS: Montelukast, fluticasone,
and salmeterol suppressed H2O2-induced ROS production. Indacaterol enhanced H2O2
induced ROS production. Budesonide and formoterol alone had no anti-ROS effects,
but the combination of these two drugs significantly suppressed H2O2-induced ROS
production. CONCLUSIONS: Different asthma medications have different anti-ROS
effects on monocytes. The combination therapy with LABA and ICS seemed not to be
the only choice for asthma control. Montelukast may also be a good supplemental
treatment for the poorly controlled asthma because of its powerful anti-ROS
effects. Our findings provide a novel therapeutic view in asthma.
PMID- 28696795
TI - Decoy receptor 3 down-regulates centrosomal protein 70 kDa specifically in
rheumatoid synovial fibroblasts.
AB - OBJECTIVES: Decoy receptor 3 (DcR3) competitively binds to Fas ligand,
lymphotoxin-related inducible ligand that competes for glycoprotein D binding to
herpes virus entry mediator on T cells (LIGHT) and TNF-like ligand 1A (TL1A),
thereby preventing their effects. Using a microarray assay, we previously newly
identified centrosomal protein 70 kDa (CEP70) as one of the genes whose
expression in fibroblast-like synoviocytes from patients with rheumatoid
arthritis (RA-FLS) is reduced by DcR3. Here, we investigated the significance of
DcR3 regulation of CEP70 for RA-FLS. METHODS: Synovial samples were obtained from
RA patients who had never been treated with biologics and from osteoarthritis
(OA) patients. CEP70 mRNA expression was quantified using RT-qPCR analysis. CEP70
protein expression was assessed using immunohistochemical and western blot
analyses. RESULTS: CEP70 was expressed predominantly in the superficial lining
layer in RA synovial tissue. CEP70 expression was dose-dependently downregulated
by DcR3-Fc in RA-FLS but was not downregulated in OA-FLS. TL1A antibody prevented
the DcR3-Fc inhibitory effects on CEP70 expression in RA-FLS. CONCLUSIONS: These
results indicated that DcR3 reduces CEP70 expression in RA-FLS by binding to
membrane-bound TL1A and may suppress RA-FLS proliferation. The reduction in CEP70
expression by DcR3/TL1A signaling may control the hyperplasia of RA synovium.
PMID- 28696796
TI - LNG-IUS 12: a 19.5 levonorgestrel-releasing intrauterine system for prevention of
pregnancy for up to five years.
AB - INTRODUCTION: Globally, intrauterine devices (IUDs) are the second most commonly
used form of reversible contraception because of their high efficacy, safety,
convenience and cost effectiveness. The levonorgestrel releasing intrauterine
system with daily average release of 20 mcg (LNG-IUS 20) is the popular choice
because of its favorable bleeding patterns and many noncontraceptive benefits. A
three year (LNG-IUS 8) became available three years ago. More recently, the LNG
IUS 12 was added. This new IUD shares a smaller frame, narrow inserter and lower
rate of amenorrhea with the LNG-IUS 8, but it offers the five years of
contraceptive protection of the LNG-IUS 20. Areas covered: This article provides
information on the contraceptive efficacy, safety and tolerability of this new
IUS based on approximately 60,000 cycles of use. Where available, the impacts of
subject age, parity and body mass index (BMI) on study outcomes are reported.
Expert opinion: This new LNG-IUS 12 with mid-dose hormone levels, smaller frame
and longer effective life fills a niche that may better meet the needs of women
who might appreciate the narrow insertion tube and/or the lower rates of
amenorrhea. Cost will ultimately help determine success.
PMID- 28696797
TI - Cancer costs and outcomes in the Finnish population 2004-2014.
AB - INTRODUCTION: The cost of cancer and outcomes of cancer care has been much
debated, since cancer represents 3-6% of total healthcare costs. The objective of
this study was to analyse the development of the costs and outcomes in Finland
between 2004 and 2014. MATERIAL AND METHODS: The national cost, episodes and
outcomes data were obtained from the national register databases. Two hospitals
were used to validate the costs of care. The outcome measures included relative
survival rate, mortality, sick leave days per patient and number of new
disability pensions. RESULTS: The total cost of cancer in 2014 was 927 million ?.
The real costs increased by 1.7% per year over the period studied, while the cost
per new cancer patient decreased. The relative survival rate was enhanced by 7%,
and the number of sick leave days and new disability pensions per cancer patient
was reduced. The share occupied by cancer treatment in total healthcare costs
decreased slightly from 3.7% to 3.6%, indicating that cancer care has not become
more expensive compared to the treatment of other diseases. CONCLUSIONS: This is
the first survey to analyse the change in actual cancer costs and outcomes in the
population-level within a 10-year period. Since cancer care outcomes in Finland
have been among the best in Europe, the progress in terms of the costs and the
conversions in the cost distributions across categories are significant and
valuable sources for international comparisons.
PMID- 28696798
TI - Severer lupus erythematosus-like skin lesions in MRL/lpr mice with homozygous
Kitwsh/wsh mutation.
AB - OBJECTIVE: To clarify the roles of mast cells (MCs) on the pathogenesis of lupus
erythematosus (LE)-like skin lesions on MRL/lpr mice. METHODS: MRL/lpr mice were
mated with C57BL/6-Kitwsh/wsh mice and the heterozygous F1 mice were 10 times
backcrossed with the parental MRL/lpr to generate MRL/lpr-Kitwsh/wsh mice. MC
deficient MRL/lpr-Kitwsh/wsh mice were compared with MRL/lpr-Kit+/+ and MRL/lpr
Kitwsh/+ mice with intact MCs. RESULTS: MRL/lpr-Kitwsh/wsh mice developed skin
lesions without infiltrating MCs. As similar skin lesions on MRL/lpr-Kit+/+ mice
and MRL/lpr-Kitwsh/+ mice contain comparable number of MCs, these mice were
collectively analyzed as MRL/lpr mice with MCs. Compared with MRL/lpr mice with
MCs, skin lesions developed earlier and showed consistently higher severity, with
significantly higher mRNA expressions of many inflammatory cytokines in the
dorsal skin on MRL/lpr mice without MCs. Furthermore, survival rate was
significantly lower in MRL/lpr mice without MCs. The number of infiltrating MCs
significantly increased in association with the severity of skin lesions in
MRL/lpr mice with MCs. CONCLUSIONS: These results demonstrated that MCs are
infiltrated to suppress the progression of LE-like skin lesions in MRL/lpr mice.
PMID- 28696799
TI - Levator resection for congenital ptosis: Does pre-operative levator function or
degree of ptosis affect successful outcome?
AB - The aim of this study was to determine whether pre-operative levator function and
degree of ptosis affect surgical outcomes in children with congenital ptosis
undergoing anterior levator resection under general anaesthesia. Retrospective
cohort study. Children with 'simple' congenital ptosis who underwent anterior
levator resection under general anaesthesia. Consecutive cases were reviewed with
regards to achievement of the desired lid height (surgical success), and the
influence of preoperative levator function and degree of ptosis. The amount of
pre-operative levator function and degree of ptosis, with corresponding surgical
outcomes. Forty-two lids (37 patients) were included in the study: 36 primary and
6 revision cases (which were excluded from analysis due to small sample size).
Mean age was 7 years (range 3-17 years), with similar male to female ratio
(1.2:1). The overall success rate for primary was 86%. There were small to
moderate trends towards greater amount of levator resection for lower levator
function (r2 = -0.25, p < 0.05) and higher degree of ptosis (r2 = 0.38, p <
0.05). All successful primary cases (n = 31) had pre-operative levator function
of at least 8 mm. Levator resection in children under general anaesthesia
continues to be an imprecise science. Degree of ptosis and levator function were
poorly correlated to each other; however, there was an expected small to moderate
correlation between resection amount and levator function (negative correlation)
or degree of ptosis (positive correlation). Patients with levator function of 8mm
or more are likely to have a successful outcome.
PMID- 28696800
TI - Effect of nintedanib on airway inflammation and remodeling in a murine chronic
asthma model.
AB - INTRODUCTION: Nintedanib is a multi-tyrosine kinase receptor inhibitor recently
approved for treatment of idiopathic pulmonary fibrosis. Although angiogenesis is
a key process involved in airway structural changes in patients with bronchial
asthma, the effect of nintedanib targeting the angiokinase pathway on airway
inflammation and remodeling has not been evaluated. METHODS: We used a 3-month
ovalbumin (OVA) challenge mouse model of airway remodeling. Nintedanib was orally
administrated during the challenge period, and the effects were examined based on
the percentage of airway inflammatory cells, airway hyper-reactivity (AHR),
peribronchial goblet cell hyperplasia, total lung collagen and smooth muscle
area. The expression of growth factor receptors was analyzed in mice lung
tissues. RESULTS: The OVA challenged group showed a significant increase in
airway eosinophilic inflammation, elevated Th2 cytokines, AHR, and airway
remodeling compared to those in the control group. The airway remodeling process,
as evaluated by goblet cell hyperplasia, total lung collagen level, and airway
smooth muscle area, was suppressed by nintedanib compared to that by OVA.
Nintedanib effectively suppressed the phosphorylation of vascular endothelial
growth factor/ platelet derived growth factor subunit2/fibroblast growth factor3
receptors in the mice lung. CONCLUSIONS: Nintedanib effectively ameliorated
airway inflammation and remodeling in an OVA-induced chronic asthma model. These
results suggest that nintedanib could be a new treatment agent targeting airway
remodeling in patients with severe asthma.
PMID- 28696801
TI - Analysis of the risk of infection in patients with chronic lymphocytic leukemia
in the era of novel therapies.
AB - We studied the risk of infections in patients with chronic lymphocytic
leukemia/small lymphocytic lymphoma (CLL). Major infections were defined as
requiring hospital admission or intravenous antimicrobial treatment. Incidence
rate (IR) ratios (IRR) were used to compare infection rates. Of 263 CLL patients
followed for 936.9 person-years, 60% required treatment for progressive CLL (66
received ibrutinib). Infections occurred in 71.9% patients (IR 92.4/100 person
years) with 31.9% having major infections (IR 20.3/100 person-years) and
infections causing 37.5% of deaths. CLL treatment was associated with
significantly higher risk of major (IRR 3.31, 95% CI 2.10, 5.21) and minor (IRR
1.78, 95% CI 1.43, 2.22) infections. Compared to their previous
chemoimmunotherapy patients receiving salvage ibrutinib therapy (n = 47) had a
significantly increased risk of a major infection (IRR 2.35 95% CI 1.27, 4.34).
The risk of infection in CLL patients remains high even with use of less
immunosuppressive therapies.
PMID- 28696802
TI - Correlation of induced sputum eosinophil levels with clinical parameters in mild
and moderate persistent asthma in children aged 7-18 years.
AB - BACKGROUND: Treatment decisions in asthma are currently based on clinical
assessment and spirometry. Sputum eosinophil, being a marker of airway
inflammation, can serve as a tool for assessing severity and response to
treatment in asthma patients. OBJECTIVES: To measure eosinophil percentage in
induced sputum in children with asthma and correlate it with clinical asthma
parameters. METHODS: A prospective observational study was performed at tertiary
care hospital on 91 children aged 7-18 years with newly diagnosed mild or
moderate persistent asthma. Theinduced sputum eosinophil percentage was obtained
at the time of enrollment and three months after treatment with inhaled
budesonide. Patients were specifically evaluated for five clinical parameters of
asthma, i.e., days of acute exacerbations, use of salbutamol as rescue
medication, emergency visits, nighttime cough and days of school absence.
RESULTS: Sputum eosinophil percentage was high (3.1 +/- 0.515%) at the time of
enrollment which reduced significantly after three months of inhaled budesonide
therapy [0.06 +/- 0.164% (p < 0.0005)]. Children with moderate persistent asthma
had significantly higher values of sputum eosinophil levels than children with
mild persistent asthma at the time of enrollment (3.38 +/- 0.64% vs. 2.99 +/-
0.42%, p = 0.001) but the difference was not significant after three months of
inhaled steroid therapy (0.07 +/- 0.18 vs. 0.04 +/- 0.12, p = 0.5104). A
significant negative correlation was found between reduction in sputum eosinophil
levels and improvement in FEV1 (r = -0.400, p = 0.0001). All the clinical asthma
parameters also correlated significantly with the reduction in sputum eosinophil
levels after three months of inhaled steroid therapy. CONCLUSION: Eosinophil
levels in induced sputum correlate well with clinical asthma parameters and
asthma severity in children. It is a simple, noninvasive and cheap method which
can be used for the monitoring of asthma in a resource-limited setting.
PMID- 28696803
TI - Thai pediatricians' current practice toward childhood asthma.
AB - BACKGROUND: Childhood asthma is a substantial health burden in Thailand. Due to a
lack of pediatric respiratory specialists (pediatric pulmonologists and
allergists; RS), most Thai children are cared for by general pediatricians
(pediatric primary care providers (PCP)). OBJECTIVES: We investigated whether
current practices of Thai pediatricians complied with asthma guidelines and
compared practices (diagnosis and treatments) provided by PCP and RS. METHODS: A
cross-sectional study was conducted using electronic surveys including four case
scenarios of different asthma phenotypes distributed to Thai pediatricians.
Asthma diagnosis and management were evaluated for compliance with standard
guidelines. The practices of PCP and RS were compared. RESULTS: From 800 surveys
distributed, there were 405 respondents (51%). Most respondents (81%) were PCP,
who preferred to use clinical diagnosis rather than laboratory investigations to
diagnose asthma. For acute asthmatic attacks, 58% of the pediatricians prescribed
a systemic corticosteroid. For uncontrolled asthma, 89% of the pediatricians
prescribed at least one controller. For exercise-induced bronchospasm, 55% of the
pediatricians chose an inhaled bronchodilator, while 38% chose a leukotriene
receptor antagonist (LTRA). For virus-induced wheeze, 40% of the respondents
chose an LTRA, while 15% chose inhaled corticosteroids (ICS). PCP prescribed more
oral bronchodilators (31% vs. 18%, p = 0.02), antibiotics (20% vs. 6%, p <
0.001), and antihistamines (13% vs. 0%, p = 0.02) than RS for the management of
an acute asthmatic attack. CONCLUSIONS: Most of the Thai pediatricians' practices
toward diagnosis and treatment of acute asthmatic attack and uncontrolled asthma
conform to the guidelines. PCP prescribed more oral bronchodilators, antibiotics,
and antihistamines than RS.
PMID- 28696804
TI - Healthcare utilization by children with asthma displaced by Hurricane Katrina.
AB - OBJECTIVE: To assess the performance of TexKat, the largest Hurricane Katrina
Medicaid Emergency Waiver, in providing care to asthmatic children. METHODS:
Medicaid enrollment and encounter data for 2004 and 2006 from Louisiana and Texas
were analyzed in a pre-post comparison. Changes in utilization by children in the
waiver were compared to changes in utilization by children in Medicaid in three
control groups: children in Louisiana counties that were designated as a disaster
assistance area but who were not displaced; children in Louisiana counties that
were not designated as a disaster assistance area, and children in Texas. The
analysis included prescriptions for controller and quick-relief medications as
well as encounters in inpatient, emergency, outpatient, and office settings.
RESULTS: The sample proportion of TexKat enrollees who had a prescription filled
for controller medications fell from 0.37 to 0.28 between 2004 and 2006. By
contrast, the sample proportions for the three control groups were relatively
unchanged or increased. The inferential analysis indicated that the 2004-2006
change in proportions for the TexKat group differed from the changes for each of
the three control groups (p-value < 0.001). For office and emergency department
visits, the 2004-2006 decreases in both the proportion of subjects with a visit
and the average number of visits for the TexKat group were greater than the
changes for the control groups (p-value < 0.001). CONCLUSIONS: While TexKat
appears to have largely been successful in preventing extreme utilization
disruptions, the analysis suggests that children in the program may have received
inadequate care.
PMID- 28696805
TI - Relevance of P-glycoprotein on CXCR4+ B cells to organ manifestation in highly
active rheumatoid arthritis.
AB - INTRODUCTION: In rheumatoid arthritis (RA), P-glycoprotein (P-gp) expression on
activated B cells is associated with active efflux of intracellular drugs,
resulting in drug resistance. CXCR4 is associated with migration of B cells. This
study was designed to elucidate the relevance of P-gp expression on CXCR4+ B
cells to clinical manifestations in refractory RA. METHODS: CD19+ B cells were
analyzed using flow cytometry and immunohistochemistry. RESULTS: P-gp was highly
expressed especially on CXCR4+CD19+ B cells in RA. The proportion of P-gp
expressing CXCR4+ B cells correlated with disease activity, estimated by
Simplified Disease Activity Index (SDAI), and showed marked expansion in RA
patients with high SDAI and extra-articular involvement. In highly active RA,
massive infiltration of P-gp+CXCR4+CD19+ B cells was noted in CXCL12-expressing
inflammatory lesions of RA synovitis and RA-associated interstitial pneumonitis.
In RA patient with active extra-articular involvement, intracellular
dexamethasone level (IDL) in lymphocytes diminished with expansion of P-gp+CXCR4+
CD19+ B cells. Adalimumab reduced P-gp+CXCR4+ CD19+ B cells, increased IDL in
lymphocytes, and improved the clinical manifestation and allowed tapering of
concomitant medications. CONCLUSIONS: Expansion of P-gp+CXCR4+ B cells seems to
be associated with drug resistance, disease activity and progressive destructive
arthritis with extra-articular involvement in RA.
PMID- 28696806
TI - Measuring personal recovery - psychometric properties of the Swedish
Questionnaire about the Process of Recovery (QPR-Swe).
AB - BACKGROUND: Personal recovery, defined as an individual process towards meaning,
is an important target within mental health services. Measuring recovery hence
requires reliable and valid measures. The Process of Recovery Questionnaire (QPR)
was developed for that purpose. AIMS: The aim was to develop a Swedish version of
the QPR (QPR-Swe) and explore its psychometric properties in terms of factor
structure, internal consistency, construct validity and sensitivity to change.
METHODS: A total of 226 participants entered the study. The factor structure was
investigated by Principal Component Analysis and Scree plot. Construct validity
was addressed in terms of convergent validity against indicators of self-mastery,
self-esteem, quality of life and self-rated health. RESULTS: A one-factor
solution of QPR-Swe received better support than a two-factor solution. Good
internal consistency was indicated, alpha = 0.92, and construct validity was
satisfactory. The QPR-Swe showed preliminary sensitivity to change. CONCLUSIONS:
The QPR-Swe showed promising initial psychometric properties in terms of internal
consistency, convergent validity and sensitivity to change. The QPR-Swe is
recommended for use in research and clinical contexts to assess personal recovery
among people with mental illness.
PMID- 28696807
TI - Association between polycystic ovary syndrome and the risk of stroke and all
cause mortality: insights from a meta-analysis.
AB - Many epidemiologic literatures have investigated the link between PCOS and long
term stroke risk and all-cause mortality, but the results are surprisingly
conflicting. A meta-analysis was performed to examine the link between polycystic
ovary syndrome (PCOS) and the risk of stroke, death from any cause, and assessed
whether BMI might explain a higher risk of stroke. We searched the PUBMED,
EMBASE, and Cochrane Library databases with no restrictions. Nine Cohort studies
were identified, involving a total of 237,647 subjects. Compared with those
without PCOS, subjects with PCOS were significantly associated with a increased
risk of developing stroke (OR = 1.36; 95% CI 1.09-1.70; p = .007). However, no
significant association was observed between PCOS and all-cause death (OR = 1.21;
95% CI 0.88-1.66; p = .25). Moreover, after pooling the five studies with risk
estimates adjusted for BMI, the association between PCOS and stroke was slightly
attenuated, although the odds ratios did not reach statistical significance (OR =
1.24; 95% CI 0.98-1.59). In conclusion, PCOS is associated with significant
increased risk for stroke, while there is no consistent evidence to indicate that
PCOS influences all-cause death outcomes. Increased BMI is an important
contributor to the relationship between PCOS and stroke risk. Further study is
needed to clarify which subgroups of subjects with the PCOS are at higher risk
for stroke and should focus on developing reliable device for risk
stratification.
PMID- 28696808
TI - Bone morphogenetic protein 7-transduced human dermal-derived fibroblast cells
differentiate into osteoblasts and form bone in vivo.
AB - BACKGROUND: Human dermal-derived fibroblast cells (hDDFCs) are multipotent. Bone
morphogenetic proteins (BMPs) are a group of cytokines that promote different
developmental processes, including the formation of bone. BMPs can promote hDDFC
osteogenesis, but the role of BMP7 in hDDFC osteogenesis in vitro and bone
formation in vivo has not been investigated in depth. MATERIALS AND METHODS:
hDDFCs were stably transfected with a human BMP7 recombinant adenovirus and
osteogenic differentiation was examined by alkaline phosphatase staining and
calcium accumulation. In addition, we measured the expression of osteoblast
related genes. To examine osteogenesis in vivo, we injected C57BL/6 nude mice
with adenovirus-transfected hDDFCs in a calcium alginate hydrogel and examined
bone formation using soft X-ray, histological, and immunohistochemical analyses.
RESULTS: Our findings showed that adenovirus-mediated BMP7 expression promoted
osteogenic differentiation of hDDFCs and enhanced expression of osteoblast
related genes in vitro. Cells infected with BMP7 adenoviruses showed enhanced
bone formation and osteoblast-related gene expression in vivo after the injection
of hDDFC-hydrogel mixture. CONCLUSIONS: Taken together, our data indicate that
BMP7 significantly promotes hDDFC osteogenesis, and confirm that infecting hDDFCs
with BMP7-expressing adenoviruses is a useful tool for bone tissue engineering.
PMID- 28696809
TI - Effects of Aspergillus fumigatus on glucocorticoid receptor and beta2-adrenergic
receptor expression in a rat model of asthma.
AB - PURPOSE: Conventional inhaled corticosteroids or beta2-adrenergic receptor
agonists do not work well in some asthmatic populations while empirical
antifungal therapy has obvious impact on those patients. The study was designed
to investigate whether short-term exposure to Aspergillus fumigatus (A.
fumigatus) could decrease glucocorticoid receptor (GCR) and beta2-adrenergic
receptor (ADRB2) expression in lung tissue of asthmatic rats. MATERIALS AND
METHODS: A rat model of chronic asthma was first established by ovalbumin
sensitization and challenge. Rats with chronic asthma were then exposed to short
term application of A. fumigatus spores. Airway hyper-responsiveness, eosinophil
ratio in bronchoalveolar lavage (BAL) fluid and total IgE in serum were counted
in these experimental animals. GCR and ADRB2 expression in the lung were detected
and analyzed. Furthermore, the levels of toll-like receptors (TLRs) 2, 3 and 4 in
lung tissue were measured. RESULTS: Short-term exposure to A. fumigatus could
down-regulate the expression of GCR, aggravate airway hyper-responsiveness and
increase the level of TLR2 in rats with asthma. There were no obvious changes in
the levels of ADRB2 expression, recruited eosinophils, total IgE, TLR3 and TLR4
after application of A. fumigatus in asthmatic rats. CONCLUSIONS: These findings
indicate that A. fumigatus exposure may be involved in glucocorticoids
unresponsiveness by down-regulating the expression of GCR in asthmatics. The
possibility of A. fumigatus colonization or infection should not be ignored in
patients of steroid-resistant asthma.
PMID- 28696810
TI - Mitochondrial DNA variations are associated with recurrent pregnancy loss.
AB - Cases with three or more consecutive spontaneous abortions before the 20th week
of gestation are termed as recurrent pregnancy loss (RPL). Problems in
implantation of the foetus and any retarded growth of the foetus in the uterus
can be correlated to RPL. Possible causes of RPL would include the genetic
variations in the regulatory enzymes of the crucial metabolic pathways, clotting
factors, hormones and hormone receptors. This defect of the mitochondrial
respiratory chain is recognized as a major cause of human disease. We
investigated 73 women with RPL and 100 healthy normal controls. By using the
direct sequencing method, the amplified products including the mtDNA complex I
genes were analyzed. Overall, seven variations in mitochondrial complex I genes
were found (T4216C, A5153G, C10142T, C12062T, A12662G, G14179A and T14263C) using
direct sequencing technique. The RPL group had significantly higher proportions
of the different variants than those observed of the control group. In
conclusion, more research is essentially needed to understand the effect and role
of the mitochondrial variations in the progress of RPL, which may vary among
individuals and different ethnic groups.
PMID- 28696811
TI - Prevalence, clinical characteristics and morbidity of the Asthma-COPD overlap in
a general population sample.
AB - OBJECTIVE: Although asthma and chronic obstructive pulmonary disease (COPD) have
been regarded as distinct conditions, emerging literature suggests that
overlapping phenotypes, called asthma-COPD overlap (ACO), exists. The aim of this
study was to describe prevalence, patient characteristics and morbidity of ACO.
METHODS: From a cross-sectional population sample, the West Sweden Asthma Study,
subjects with suspected asthma, chronic bronchitis or COPD, and a random sample,
were invited to clinical examinations. ACO was defined as doctor-diagnosed
asthma, or clear clinical signs of asthma at examination, with a FEV1/FVC < 0.7.
RESULTS: Subjects were categorized as ACO (N = 181), COPD only (N = 89), asthma
only (N = 651) or healthy (n = 1036) based on clinical examinations. Prevalence
of ACO was 3.4% in the random sample (N = 1172) and 18.1% among asthmatics (N =
138) in the random sample. Subjects with ACO (mean age 59 years, 54% women) had
an age and gender distribution in between asthma only (45 years, 63% women) and
COPD only (62 years, 41% women). Ever-smoking was reported by 71%, 48% and 74% in
the ACO, asthma only and COPD only groups, respectively. Subjects with ACO had
worse lung function (mean FEV1% of predicted normal 76%) than asthma only (100%)
and COPD only (87%) and reported more respiratory symptoms. Also respiratory
related emergency visits were more common in ACO compared to asthma only and COPD
only, respectively. CONCLUSIONS: ACO is present in 3.4% of the population and
common among subjects with both asthma and COPD. Subjects with ACO had worse lung
function and more symptoms than subjects with asthma or COPD only.
PMID- 28696812
TI - A phase I trial of bortezomib in combination with everolimus for treatment of
relapsed/refractory non-Hodgkin lymphoma.
AB - B-cell non-Hodgkin lymphomas (NHL) display dysregulation of pathways controlling
cell proliferation and apoptosis. Combined proteasome and mTOR inhibition,
demonstrated with bortezomib and everolimus in a preclinical model, thus warrants
evaluation in humans. We conducted a phase I study to identify the maximum
tolerated dose (MTD) and safety of this combination in relapsed/refractory (r/r)
NHL. Twenty-nine patients were enrolled from July 2008 to March, 2015. Toxicities
were primarily hematologic, and dose-limiting thrombocytopenia defined the MTD as
5 mg everolimus daily with 1.3 mg/m2 bortezomib d1, 4, 8, and 11 every 21 days.
Of 25 response-evaluable patients there was one complete response in a patient
with MCL and three partial responses (two MCL, one FL) for an overall response
rate of 16%. In conclusion, the combination of everolimus and bortezomib results
in dose limiting thrombocytopenia, but is tolerable. This combination has limited
clinical activity in heavily pretreated NHL.
PMID- 28696813
TI - Liposomal prednisolone phosphate potentiates the antitumor activity of liposomal
5-fluorouracil in C26 murine colon carcinoma in vivo.
AB - The antitumor efficacy of 5-fluorouracil (5-FU) in advanced colorectal cancer
(CRC) is hindered not only by the low therapeutic index, but also by tumor cell
resistance to this cytotoxic drug. Therefore, to enhance the 5-FU antitumor
activity, the present research used a novel tumor-targeted therapy based on the
co-administration of 5-FU encapsulated in long-circulating liposomes (LCL-5-FU)
together with liposomal prednisolone phosphate (LCL-PLP), a formulation with
known anti-angiogenic actions on C26 murine colon carcinoma cells. Thus, we
assessed the in vivo effects of the combined liposomal drug therapy on C26
carcinoma growth as well as on the production of molecular markers with key roles
in tumor development such as angiogenic, inflammatory, and oxidative stress
molecules. To get further insight into the polarization state of tumor
microenvironment after the treatment, we determined the IL-10/IL-12p70 ratio in
tumors. Our results showed that combined liposomal drug therapy inhibited almost
totally tumor growth and was superior as antitumor activity to both single
liposomal drug therapies tested. The antitumor efficacy of the combined therapy
was mainly related to the anti-angiogenic and anti-inflammatory actions on C26
carcinoma milieu, being favored by its controlling effect on intratumor oxidative
stress and the skewing of polarization of tumor microenvironmental cells toward
their antineoplastic phenotypes. Thus, our study unveils a promising treatment
strategy for CRC that should be furthermore considered.
PMID- 28696815
TI - Autophosphorylation of calcium/calmodulin-dependent protein kinase (CCaMK) at
S343 or S344 generates an intramolecular interaction blocking the CaM-binding.
AB - The Ca2+ and Ca2+/calmodulin-dependent protein kinase (CCaMK) is an important
effector protein of Ca2+/calmodulin-mediated signaling, and in legumes, it is a
critical regulator of plant-rhizobia and mycorrhizal symbioses. CCaMK contains a
kinase domain, a calmodulin-binding/autoinhibitory domain and a visinin-like
domain. Previous studies revealed the presence of 2 phosphorylation sites, S343
and S344, in the calmodulin-binding domain. Mutations at these sites affected the
kinase activity and downstream rhizobium and mycorrhizal symbioses, which
highlighted the importance of these residues in regulating protein activity. This
addendum further clarifies the regulation of CCaMK by identifying an
intramolecular interaction between residue(s) in the kinase domain and
phosphorylation sites S343 and S344. This interaction turns off the substrate
phosphorylation capacity of CCaMK.
PMID- 28696814
TI - Ddx19 links mRNA nuclear export with progression of transcription and replication
and suppresses genomic instability upon DNA damage in proliferating cells.
AB - The DEAD-box Helicase 19 (Ddx19) gene codes for an RNA helicase involved in both
mRNA (mRNA) export from the nucleus into the cytoplasm and in mRNA translation.
In unperturbed cells, Ddx19 localizes in the cytoplasm and at the cytoplasmic
face of the nuclear pore. Here we review recent findings related to an additional
Ddx19 function in the nucleus in resolving RNA:DNA hybrids (R-loops) generated
during collision between transcription and replication, and upon DNA damage.
Activation of a DNA damage response pathway dependent upon the ATR kinase, a
major regulator of replication fork progression, stimulates translocation of the
Ddx19 protein from the cytoplasm into the nucleus. Only nuclear Ddx19 is
competent to resolve R-loops, and down regulation of Ddx19 expression induces DNA
double strand breaks only in proliferating cells. Overall these observations put
forward Ddx19 as an important novel mediator of the crosstalk between
transcription and replication.
PMID- 28696816
TI - Pre-Existing Mesh at the Hiatus in Revisional Surgery Does Not Result in
Increased Morbidity: A Case-Control Evaluation.
AB - BACKGROUND: Mesh is sometimes used to reinforce the hiatus during primary and
reoperative fundoplication. This is a controversial practice as it is not clear
that this leads to a decreased rate of failure of the hiatal closure, and
concerns about morbidity related to the presence of mesh in this location exist.
One of these concerns is that if reoperation is ever required (fundoplication
herniates through the hiatus, for example), revisional surgery would be
significantly more difficult and associated with a higher rate of morbidity than
if mesh had not been placed at the hiatus in a previous procedure. METHODS: A
retrospective review was conducted of prospectively collected data on 104
patients to undergo surgery for a failed fundoplication between 2011 and 2015.
Fourteen patients (13.5%) had previous operations where mesh had been placed at
the hiatus and underwent a subsequent revisional procedure. Procedures performed
were reoperative fundoplication and Roux-en-Y gastric bypass as a salvage
procedure for a failed fundoplication, especially in the setting of obesity.
These 14 cases were matched 1:2 with randomly selected control patients from the
database who underwent revisional surgery in whom mesh had not been placed at the
original operation. Cases and controls were paired based on the number of
previous revision attempts and operation type. Perioperative outcomes were
compared. RESULTS: There was no statistically significant difference in 30-day
morbidity, readmission, operative time, or length of hospital stay. CONCLUSIONS:
In this retrospective case-control evaluation, mesh at the hiatus did have an
impact on morbidity or operative time.
PMID- 28696817
TI - Reference database of hematological parameters for growing and aging rats.
AB - : The normal hematological values in various phases of the rat life provide a
valuable guide to researchers and could be useful for experimental works.
However, database information available on the literature are incomplete. AIM:
This study aimed to present normal hematological parameters of young and aged
rats. METHODS: Male and female rats were distributed into seven experimental
groups with 1, 2, 3, 6, 12, 18, and 24 months of age. Blood samples taken from
the tails were analyzed. Normal hematological values were determined for each age
group. RESULTS: Rats showed a progressive weight gain with advancing age,
predominantly after 3 months of life. With advancing age, differences were found
on hematological parameters: some of them showed a progressive rise with age and
others did not. Hemoglobin levels and hematocrit did not change while the number
of circulating red blood cells suffered slight increase. CONCLUSION: The present
study determined the normal values for absolute and relative hematological
parameters in Wistar rats from 2 to 24 months for male and female rats. The
results can be used in studies of effects of aging, feeding, and medications on
growing and aging rats.
PMID- 28696818
TI - Use of Biomarkers to Guide Decisions on Adjuvant Systemic Therapy for Women With
Early-Stage Invasive Breast Cancer: American Society of Clinical Oncology
Clinical Practice Focused Update Guideline Summary.
PMID- 28696819
TI - Heterogeneity and Stability in Foxp3+ Regulatory T Cells.
AB - Foxp3+ regulatory T cells (Tregs) play an indispensable role in controlling
tolerance and immunity against self- and foreign antigens. The failure of Tregs
to properly function is the direct cause of systemic and chronic inflammation as
well as immune suppression. It is now evident that Tregs are highly heterogeneous
populations depending on the surface phenotypes, cytokine profiles, and
anatomical locations. Yet, our understanding of the cellular and molecular
pathways underlying such heterogeneity is very limited. Furthermore, some Tregs
lose the phenotype (and suppressive functions) and instead acquire pathogenicity.
Since utilizing Tregs as a tool for immunotherapy is being implemented in many
clinical settings, it is of utmost importance to understand the precise
mechanisms by which the loss of Treg phenotype (and function) is prevented. In
this review, both cellular and molecular factors involved in Treg heterogeneity
and stability are discussed.
PMID- 28696820
TI - Viral interactions with host cell Rab GTPases.
AB - Viruses are obligate intracellular parasites that utilize cellular machinery for
many aspects of their replication cycles. Enveloped viruses generally rely upon
host vesicular trafficking machinery to direct their structural proteins and
genomes to sites of virus replication, assembly, and budding. Rab GTPases have
been implicated in the replication of many important viral pathogens infecting
humans. This review provides a summary of virus-Rab protein interactions, with a
particular focus on the role of Rab-related trafficking pathways on late events
in the lifecycle of herpesviruses and of HIV-1.
PMID- 28696821
TI - Multifaceted role of SMCR8 as autophagy regulator.
AB - Through autophagy intracellular material is engulfed by double membrane vesicles
and delivered to lysosomes for degradation. This process requires Rab GTPases,
Rab GAPs and Rab GEFs for proper membrane trafficking, since they control vesicle
budding, targeting and fusion. Deregulation of autophagy contributes to several
human diseases including cancer, bacterial or viral infections and
neurodegeneration. This review focuses on the complex roles of the newly
identified protein SMCR8 and its interaction partners during formation and
maturation of autophagosomes as well as regulation of lysosomal function and
further discusses their implication in neurodegenerative diseases such as ALS and
FTD.
PMID- 28696822
TI - The Balance of Tissue Inhibitor of Metalloproteinase-1 and Matrix
Metalloproteinase-9 in the Autoimmune Inner Ear Disease Patients.
AB - Tissue inhibitor of metalloproteinase-1 (TIMP-1) is a protein implicated in the
control of inflammation in a number of autoimmune diseases. We hypothesized that
the balance of TIMP-1 and matrix metalloproteinase-9 (MMP-9) may influence the
control or perpetuation of inflammation in corticosteroid-responsive (RES) and
corticosteroid-resistant (NR) autoimmune inner ear disease (AIED) patients. In
the present study, we observed that plasma from AIED patients exhibited greater
levels of TIMP-1 values compared with normal healthy controls. TIMP-1 abrogates
lipopolysaccharide-mediated interleukin (IL)-1beta release from peripheral blood
mononuclear cells in a dose-dependent manner. RES AIED patients have higher basal
TIMP-1 levels and produce more TIMP-1 in response to IL-1beta. Conversely,
consistent with our previous studies, we found that NR patients have higher basal
MMP-9 levels and produce more MMP-9 levels in response to IL-1beta.
PMID- 28696823
TI - Effects of resistance training on liver structure and function of aged rats.
AB - : The aging process may cause negative physiological changes. However, exercises
as resistance training (RT) have been considered an important intervention to
attenuate these changes. Additionally, liver plays an important role in blood
glucose homeostasis in exercise. AIM: This study aimed to analyze the effects of
RT on the liver components of aged animals. METHODS: Male Wistar rats were
divided into two groups: 24 months' group (CONTROL); and group submitted to a
progressive RT protocol for 16 weeks (EXERCISE). Both groups were sacrificed at
24 months. RESULTS: We observed a decrease in blood flow due to the practice of
resistance exercises. Besides, our results showed that hepatic tissue plays an
important role in glycemic homeostasis during RT. In addition, RT increased
mitogen capacity of hepatocytes. CONCLUSIONS: Our study showed many implications
for the knowledge about the effects of strength training on old animals' liver.
PMID- 28696824
TI - Age-appropriate versus up-to-date coverage of routine childhood vaccinations
among young children in Israel.
AB - BACKGROUND AND AIMS: Routine childhood vaccinations schedules recommend that
children receive the vaccine doses at specific ages. Vaccination coverage data
are conventionally reported by the up-to-date method. We aimed to assess
vaccination timeliness by the age-appropriate method and compare with the up-to
date vaccination coverage. METHODS: Assessment of age-appropriate and up-to-date
vaccination coverage among children born in Israel in 2009 and followed to age 48
months (national representative sample, n = 3892). The vaccinations included:
Hepatitis B vaccine (HBV), Diphtheria-Tetanus-acellular Pertussis-Polio
Haemophilus-influenzae-b (DTaP-IPV-Hib), Pneumococcal conjugate vaccine (PCV),
Measles-mumps-rubella-varicella vaccine (MMR/MMRV) and Hepatitis A vaccine (HAV).
The categories defined: age-appropriate (at the recommended age and up to 1
month), delayed less than 6 months, delayed 6 months and above and unvaccinated
(48 months). RESULTS: The age-specific vaccinations assessment showed
considerable delay in receipt of routine vaccination. While most (96%, 95%, 91%,
96%, 94% and 86%) children were vaccinated up-to-date for HBV3, DTaP-IPV-Hib4,
PCV3, MMR/MMRV1, HAV1and HAV2 vaccine doses; only 26%, 29%, 47%, 64%, 55% and 12%
were vaccinated age-appropriate. Vaccination delay was more common in vaccines
with multiple doses. Vaccination delay was associated with high child's birth
order, low socio-economic rank, ethnicity (delay more common in Jews vs. Arabs),
season of birth (winter) and delayed receipt of DTaP-IPV-Hib vaccine 1st dose.
CONCLUSIONS: This study assessed age-appropriate childhood vaccination coverage
in a national cohort of children. While the overall vaccination coverage stands
in line with the WHO goals, vaccination timeliness and equity are inadequate and
targeted public health intervention programs aimed at vaccination timeliness are
necessary.
PMID- 28696825
TI - Androgen status in non-diabetic elderly men with heart failure.
AB - PURPOSE: We aimed at evaluating androgen status (serum testosterone [TT] and
estimated free testosterone [eFT]) and its determinants in non-diabetic elderly
men with heart failure (HF). Additionally, we investigated its associations with
body composition and long-term survival. METHODS: Seventy three non-diabetic men
with HF and 20 healthy men aged over 55 years were studied. Echocardiography, 6
min walk test, grip strength, body composition measurement by DEXA method were
performed. TT, sex hormone binding globulin, NT-proBNP, and adipokines
(adiponectin and leptin) were measured. All-cause mortality was evaluated at six
years of follow-up. RESULTS: Androgen status (TT, eFT) was similar in elderly men
with HF compared to healthy controls (4.79 +/- 1.65 vs. 4.45 +/- 1.68 ng/ml and
0.409 +/- 0.277 vs. 0.350 +/- 0.204 nmol/l, respectively). In HF patients, TT was
positively associated with NT-proBNP (r= 0.371, p = 0.001) and adiponectin levels
(r = 0.349, p = 0.002), while inverse association was noted with fat mass (r =
0.413, p < 0.001). TT and eFT were independently determined by age, total fat
mass and adiponectin levels in elderly men with HF (p < 0.05 for all). Androgen
status was not predictor for all-cause mortality at six years of follow-up.
CONCLUSIONS: In non-diabetic men with HF, androgen status is not altered and is
not predictive of long-term outcome.
PMID- 28696826
TI - A Comparative Study on Surgical Outcomes of Glued Intraocular Lens and Sutured
Scleral Fixated Intraocular Lens Implantation.
AB - PURPOSE: To compare the surgical outcomes of glued intraocular lens (GIOL) and
sutured scleral fixated intraocular lens (SFIOL) implantation. METHODS: A
retrospective, interventional case series of 60 patients (68 eyes) who underwent
GIOL (28 eyes: 11 primary; 17 secondary) and SFIOL (40 eyes: 24 primary; 16
secondary) in a tertiary eye care institute was done. The main outcome measures
were complications, time taken for surgery, postoperative refractive outcomes,
and final best-corrected visual acuity (BCVA). RESULTS: The mean final BCVA was
0.42 (20/40) (+/- SD 0.29) in the GIOL group and 0.57 (20/50) (+/- SD 0.48) in
the SFIOL group (p=0.08). The time taken for primary GIOL (mean+/- SD: 66+/-19
minutes) was significantly lower than primary SFIOL (means+/-SD: 94+/-34 minutes)
(p=0.006). The complications were comparable between the GIOL (25%) and SFIOL
(15%) groups (p=0.30). The most common complication noted was transient vitreous
hemorrhage (GIOL 17%, SFIOL 5%). The only sight-threatening complication seen was
retinal detachment, with one eye in each group. The mean follow-up was 20 (GIOL)
and 20.4 weeks (SFIOL). CONCLUSION: Both glued intraocular lens and sutured
scleral fixated intraocular lens are safe and effective procedures in cases of
insufficient capsular support. In view of the shorter surgical time with similar
outcomes, primary GIOL can be considered as a preferred surgical option over
primary SFIOL.
PMID- 28696827
TI - Isolation of Rab5-positive endosomes reveals a new mitochondrial degradation
pathway utilized by BNIP3 and Parkin.
AB - Degradation of mitochondria is an important cellular quality control mechanism
mediated by two distinct pathways: one involving Parkin-mediated ubiquitination
and the other dependent on mitophagy receptors. It is known that mitochondria are
degraded by the autophagy pathway; however, we recently reported that the small
GTPase Rab5 and early endosomes also participate in Parkin-mediated mitochondrial
clearance. Here, we have developed a protocol to isolate Rab5-positive vesicles
from cells for proteomics analysis and provide additional data confirming that
mitophagy regulators and mitochondrial proteins are present in these vesicles. We
also demonstrate that the mitophagy receptor BNIP3 utilizes the Rab5-endosomal
pathway to clear mitochondria in cells. These findings indicate that a redundancy
exists in the downstream degradation pathways to ensure efficient mitochondrial
clearance.
PMID- 28696829
TI - Unraveling a model of TCL/RhoJ allosterism using TC10 reverse chimeras.
AB - In addition to the classical regulation of GTPase activity by effector proteins,
investigating the variations in the amino acid sequence and structures of GTPases
often provides insights into regulatory mechanisms that are more GTPase-specific.
TCL/RhoJ is a Rho GTPase most closely related to Cdc42 and TC10; however, its
nucleotide exchange activity is distinctly influenced by N-terminal amino acids
17-20 and the more distal amino acids 121-129. In this short study, we have
further explored the differences between TCL and its homolog TC10 and show that
its unique mode of allosteric regulation requires broader diversification of its
amino acid sequence than previously appreciated.
PMID- 28696828
TI - Small molecule inhibitor TW-37 is tolerable and synergistic with chemotherapy in
nasopharyngeal carcinoma.
AB - Chemotherapy is a crucial adjuvant therapy of advanced nasopharyngeal carcinoma
(NPC). However, enhancing sensitivity and tolerance of chemotherapeutics in NPC
treatment have been challenging. Both Bcl-2 and Mcl-1, 2 pro-survival proteins of
Bcl-2 family, play essential roles on the chemotherapy tolerance of numerous
cancers. In the present study, we explored the influences of TW-37, a small
molecule inhibitor of Bcl-2 and Mcl-1, on the efficiency of chemotherapy for NPC.
Oncomine cancer database shows that NPC tissues have higher expression of Bcl-2
and Mcl-1 than those of normal nasopharyngeal epithelial (NPE) tissues. And our
results reveal that chemotherapeutics, Cisplatin (CDDP) and 5-Fluoracil (5-FU),
result in the greater decrease of protein level of Bcl-2 and Mcl-1 in NPC cells
than those in NPE cells. TW-37 does not have significant impact on the
chemotherapeutics-treated NPE cell viability at a dosage that efficiently reduces
chemotherapeutics-treated NPC cell viability. Moreover, impacts of TW-37 on the
cell viability of chemotherapeutics-treated NPC cells are dependent on the
expression of Bcl-2 and Mcl-1 in NPC cells. Further explorations suggest that TW
37 prominently promotes apoptosis in NPC cells under chemotherapeutics treatments
but not in NPE cells. Meanwhile, TW-37 also remarkably reduces colony formation
ability of chemotherapeutics-treated NPC cells. Importantly, in vivo models, TW
37 observably increases chemosensitivity of NPC tumors but has not markedly
influence on the normal tissues in mice. In conclusion, our results point to TW
37 as a promising ancillary drug for the chemotherapy of NPC.
PMID- 28696830
TI - Influence of Temperature on the Efficacy of Homologous and Heterologous DNA
Vaccines against Viral Hemorrhagic Septicemia in Pacific Herring.
AB - Homologous and heterologous (genogroup Ia) DNA vaccines against viral hemorrhagic
septicemia virus (genogroup IVa) conferred partial protection in Pacific Herring
Clupea pallasii. Early protection at 2 weeks postvaccination (PV) was low and
occurred only at an elevated temperature (12.6 degrees C, 189 degree days), where
the relative percent survival following viral exposure was similar for the two
vaccines (IVa and Ia) and higher than that of negative controls at the same
temperature. Late protection at 10 weeks PV was induced by both vaccines but was
higher with the homologous vaccine at both 9.0 degrees C and 12.6 degrees C.
Virus neutralization titers were detected among 55% of all vaccinated fish at 10
weeks PV. The results suggest that the immune response profile triggered by DNA
vaccination of herring was similar to that reported for Rainbow Trout
Oncorhynchus mykiss by Lorenzen and LaPatra in 2005, who found interferon
responses in the early days PV and the transition to adaptive response later.
However, the protective effect was far less prominent in herring, possibly
reflecting different physiologies or adaptations of the two fish species.
Received August 1, 2016; accepted March 10, 2017.
PMID- 28696831
TI - Preliminary testing by adults of a haptics-assisted robot platform designed for
children with physical impairments to access play.
AB - Development of children's cognitive and perceptual skills depends heavily on
object exploration and experience in their physical world. For children who have
severe physical impairments, one of the biggest concerns is the loss of
opportunities for meaningful play with objects, including physical contact and
manipulation. Assistive robots can enable children to perform object manipulation
through the control of simple interfaces. Touch sensations conveyed through
haptic interfaces in the form of force reflection or force assistance can help a
child to sense the environment and to control a robot. A robotic system with
forbidden region virtual fixtures (VFs) was tested in an object sorting task.
Three sorting tasks-by color, by shape, and by both color and shape-were
performed by 10 adults without disability and one adult with cerebral palsy.
Tasks performed with VFs were accomplished faster than tasks performed without
VFs, and deviations of the motion area were smaller with VFs than without VFs.
For the participant with physical impairments, two out of three tasks were slower
with the VFs. This implies that forbidden region VFs are not always able to
improve user task performance. Alignment with an individual's unique motion
characteristics can improve VF assistance.
PMID- 28696832
TI - The Development and Acceptability of a Mobile Application for Tracking Symptoms
of Heart Failure Among Older Adults.
AB - PURPOSE: Heart failure (HF) is common in older adults. With increases in
technology use among older adults, mobile applications may provide a solution for
older adults to self-manage symptoms of HF. This article discusses the
development and acceptability of a HF symptom-tracking mobile application (HF
app). METHODOLOGY: The HF app was developed to allow patients to track their
symptoms of HF. Thirty (N = 30) older adults completed an acceptability survey
after using the mobile app. The survey used Likert items and open-ended feedback
questions. RESULTS: Overall, the acceptability feedback from users was positive
with participants indicating that the HF app was both easy to use and understand.
Participants identified recommendations for improvement including additional
symptoms to track and the inclusion of instructions and reminders. CONCLUSION: HF
is common in older adults, and acceptability of mobile apps is of key importance.
The HF app is an acceptable tool for older patients with HF to self-manage their
symptoms, identify patterns, and changes in symptoms, and ultimately prevent HF
readmission.
PMID- 28696833
TI - The intersecting cognitive and aging needs of HIV-positive older adults:
Implications for social work practice.
AB - Cognitive impairment is a significant health concern for people aging with
HIV/AIDS. Using a community-based participatory research (CBPR) framework, we
surveyed (n = 108) and interviewed (n = 20) people living with HIV who were over
age 50 about their cognitive concerns and recommendations for social work
intervention development. Quantitative findings indicate that our sample was
greatly engaged in their HIV care, yet participants had many cognitive concerns.
Qualitative findings highlighted fear, shame, and uncertainty concerning HIV and
aging alongside a need for increased social work support. This paper provides
practical engagement strategies for social workers to support clients concerning
HIV, aging, and cognition.
PMID- 28696834
TI - Simultaneous detection of the tetrachloroethylene metabolites S-(1,2,2
trichlorovinyl) glutathione, S-(1,2,2-trichlorovinyl)-L-cysteine, and N-acetyl-S
(1,2,2-trichlorovinyl)-L-cysteine in multiple mouse tissues via ultra-high
performance liquid chromatography electrospray ionization tandem mass
spectrometry.
AB - Tetrachloroethylene (perchloroethylene; PERC) is a high-production volume
chemical and ubiquitous environmental contaminant that is hazardous to human
health. Toxicity attributed to PERC is mediated through oxidative and glutathione
(GSH) conjugation metabolites. The conjugation of PERC by glutathione-s
transferase to generate S-(1,2,2-trichlorovinyl) glutathione (TCVG), which is
subsequently metabolized to form S-(1,2,2-trichlorovinyl)-L-cysteine (TCVC) is of
special importance to human health. Specifically, TCVC may be metabolized to N
acetyl-S-(1,2,2-trichlorovinyl)-L-cysteine (NAcTCVC) which is excreted through
urine, or to electrophilic metabolites that are nephrotoxic and mutagenic. Little
is known regarding toxicokinetics of TCVG, TCVC, and NAcTCVC as analytical
methods for simultaneous determination of these metabolites in tissues have not
yet been reported. Hence, an ultra-high-performance liquid chromatography
electrospray ionization tandem mass spectrometry-based method was developed for
analysis of TCVG, TCVC, and NAcTCVC in liver, kidneys, serum, and urine. The
method is rapid, sensitive, robust, and selective for detection all three
analytes in every tissue examined, with limits of detection (LOD) ranging from
1.8 to 68.2 femtomoles on column, depending on the analyte and tissue matrix.
This method was applied to quantify levels of TCVG, TCVC, and NAcTCVC in tissues
from mice treated with PERC (10 to 1000 mg/kg, orally) with limits of
quantitation (LOQ) of 1-2.5 pmol/g in liver, 1-10 pmol/g in kidney, 1-2.5 pmol/ml
in serum, and 2.5-5 pmol/ml in urine. This method is useful for further
characterization of the GSH conjugative pathway of PERC in vivo and improved
understanding of PERC toxicity.
PMID- 28696835
TI - Urinary cadmium levels in active and retired coal miners.
AB - A meta-analysis, based upon 24 publications, showed a significantly elevated risk
for urinary bladder cancer amongst miners. In European underground hard coal
mining areas, an increased risk for urinary bladder cancer development was noted
among hard coal miners, in particular in three investigations in the greater
Dortmund area. However, the cause remains unclear. As cadmium (Cd), which was
reported to be a bladder carcinogen in humans and is a constituent of coal, the
aim of this study was to determine urinary Cd levels in active and retired hard
coal miners and assess whether hard coal miners demonstrated elevated metal
levels. In total, 103 retired and 25 active hard coal miners as well as 18
controls without any history of hard coal mining were investigated for urinary Cd
levels. Urinary Cd concentrations, in addition to other elements, were analyzed
in spot urines by ICP-MS-based multi-element analysis in a Department for
Forensic and Clinical Toxicology. Limit of detection (LOD) for Cd was 0.5 MUg/L.
Reference value for occupationally non-exposed working age population was 0.8
MUg/L. In total, 49% of all underground coal miners were exposed to coal dust,
12% to grinded rock, and 39% to both. Urinary Cd levels in retired as well as
active coal miners and controls were clearly below the Biological Exposure Index.
Urinary Cd concentration is a suitable biomarker to evaluate the metallic load of
the body, as the half-life is > than 10 years. The detected urinary Cd levels in
retired and active coal miners indicated underground hard coal miners were not
apparently exposed to Cd to a occupationally-relevant concentration.
PMID- 28696836
TI - Complex families, the social determinants of health and psychosocial
interventions: Deconstruction of a day in the life of hospital social workers.
AB - The roles of hospital social workers are delineated in the literature; however,
their daily interventions have only been described anecdotally. This study
analyzes the daily work of social workers in a pediatric hospital through a
survey completed which examined factors related to interventions utilized and
time spent per case over a 1-day period. Length and types of interventions were
associated with the social determinants of health, time since diagnosis,
biopsychosocial issues, and perception of complexity. The study offers a snapshot
of the personalized expertise, provided by social workers that addresses complex
contextual and biopsychosocial concerns of patient and families.
PMID- 28696838
TI - Dying and living in the neighborhood. A street-level view of America's healthcare
promise, by P. Singh.
PMID- 28696837
TI - Japanese quail (Coturnix japonica) liver and thyroid gland histopathology as a
result of in ovo exposure to the flame retardants tris(1,3-dichloro-2-propyl)
phosphate and Dechlorane Plus.
AB - Japanese quails (Coturnix japonica) were exposed in ovo to tris(1,3-dichloro-2
propyl) phosphate (TDCIPP; 500 ng/ul), Dechlorane Plus (DP; 500 ng/ul), or a 1:1
mixture of these two to investigate the effects on liver and thyroid gland
morphology. Histological examination of 14-day-old quails showed that exposure to
TDCIPP or the mixture induced hepatic sinusoidal dilatation. No marked effects
were seen for DP alone. In addition, the mixture produced divergence of thyroid
gland follicles and proliferation of follicular cells. Our study is the first
demonstrating histopathological alterations as a result of exposure during early
development to the flame retardants TDCIPP or a TDCIPP-DP mixture suggesting the
need for further research efforts to investigate potential adverse health effects
associated with exposure to these environmental chemicals in wild birds.
PMID- 28696839
TI - Occupational bladder cancer: Polymorphisms of xenobiotic metabolizing enzymes,
exposures, and prognosis.
AB - Approximately 7% of all bladder cancer cases in males are associated with
occupation. The question arises whether the use of genome-wide association
studies was able to identify bladder cancer risk factors that may modulate
occupational bladder cancer risk and prognosis. One hundred and forty-three
bladder cancer cases with suspected occupational bladder cancer and 337 controls
were genotyped for the following polymorphisms: N-acetyltransferase 2 (NAT2),
glutathione S-transferase M1 (GSTM1), glutathione S-transferase T1 (GSTT1), UDP
glucuronyltransferase 1A rs11892031 (UGT1A), rs9642880 (close to c-MYC), and
rs710521 (close to TP63). The most relevant polymorphisms for occupational
bladder cancer risk were GSTM1 and UGT1A, especially when co-occurring (GSTM1
negative and rs11892031[A/A]: 48% cases vs. 38% controls, OR 1.47, 95% CI 0.99
2.20). The effect was more pronounced in smokers. GSTM1 negative genotype
occurred more frequently in cancer cases exposed to aromatic amines, carbolineum,
and in painters and varnishers. UGT1A (rs11892031[A/A]) was found frequently in
cases exposed to carbolineum, crack test spray, PAH, and in painters and
varnishers. All investigated polymorphisms except rs710521 (TP63) seemed to exert
an impact on recurrence risk. Relapse-free times were shorter for NAT2 slow and
ultra-slow, GSTT1 positive and GSTM1 negative cases. Occupational bladder cancer
cases with a number of risk variants displayed significantly shorter relapse-free
times compared to cases with few, less relevant risk alleles as evidenced by
median difference 8 months. In conclusion, in the present, suspected occupational
bladder cancer cases phase II polymorphisms involved in bladder carcinogen
metabolism modulate bladder cancer recurrence. Most relevant for bladder cancer
risk were GSTM1 and UGT1A but not NAT2.
PMID- 28696840
TI - Health social workers sources of knowledge for decision making in practice.
AB - This article presents findings from research examining knowledge social workers
in a health network in Victoria, Australia identified as informing their decision
making. Data for 13 patients, and in-depth interviews with six social workers who
worked with these patients, were studied. A thematic analysis of interviews
revealed that participants identified reliance on past experience and
contextual/situational information as underpinning their decisions, demonstrating
their commitment to person-in-environment perspectives. However, despite the
availability of a repository of empirical evidence, no respondent made use of
this. This study provided insight into health practitioners' sources of
knowledge, highlighting gaps and areas for further exploration.
PMID- 28696842
TI - Factors associated with in-school physical activity among urban children with
asthma.
AB - OBJECTIVE: A cross-sectional study was conducted to determine if in-school
physical activity (PA) varied by age, gender, weight and asthma status,
participation in physical education (PE), outdoor recess, and other in-school PA
among urban schoolchildren with asthma. METHODS: PA was measured by tri-axial
accelerometers. Height and mass were measured and overweight defined as BMI
>=85th percentile. Asthma impairment and risk were assessed as per national
guidelines, and asthma status variable with three categories (mild, moderate, and
severe) was created. Multivariable generalized linear mixed models adjusting for
clustering due to school and student were fitted to identify variables predictive
of PA. RESULTS: 108 children with asthma participated. Children spent 374 minutes
in school, of which 253 minutes were sedentary, 105 minutes in light PA, and 16
minutes in moderate-to-vigorous PA (MVPA). Only 3 participants reached the
recommended >=30 minutes/day of MVPA. Multivariable analysis revealed age,
gender, participation in PE class, outdoor recess, and other in-school PA as
independent predictors of PA. BMI and asthma status were not associated with PA.
CONCLUSIONS: Children with asthma were mostly sedentary at school. Older children
and girls were particularly at risk for inactivity. PE, recess, and other in
school PA participation are modifiable factors that should be targeted in school
based interventions aimed at increasing PA in this population.
PMID- 28696841
TI - International multi-site survey on the use of online support groups in bipolar
disorder.
AB - BACKGROUND: Peer support is an established component of recovery from bipolar
disorder, and online support groups may offer opportunities to expand the use of
peer support at the patient's convenience. Prior research in bipolar disorder has
reported value from online support groups. AIMS: To understand the use of online
support groups by patients with bipolar disorder as part of a larger project
about information seeking. METHODS: The results are based on a one-time, paper
based anonymous survey about information seeking by patients with bipolar
disorder, which was translated into 12 languages. The survey was completed
between March 2014 and January 2016 and included questions on the use of online
support groups. All patients were diagnosed by a psychiatrist. Analysis included
descriptive statistics and general estimating equations to account for correlated
data. RESULTS AND CONCLUSIONS: The survey was completed by 1222 patients in 17
countries. The patients used the Internet at a percentage similar to the general
public. Of the Internet users who looked online for information about bipolar
disorder, only 21.0% read or participated in support groups, chats, or forums for
bipolar disorder (12.8% of the total sample). Given the benefits reported in
prior research, clarification of the role of online support groups in bipolar
disorder is needed. With only a minority of patients using online support groups,
there are analytical challenges for future studies.
PMID- 28696843
TI - Hb Amsterdam-A1 [alpha32(B13)Met->Ile; HBA1: c.99G>A]: A Hyperunstable Variant
Due to a New Mutation on the alpha1 Gene.
AB - Patients with hyperunstable alpha chain variants usually present with a
thalassemic, rather than hemolytic, phenotype. Electrophoretic, ion exchange and
reverse phase separations usually fail to detect the variant and when DNA
sequencing identifies a 'silent' substitution it is usually presumed to be
hyperunstable. We report the identification of such a variant, alpha32(B13)Met
>Ile; HBA1: c.99G>A, arising from a new mutation on the alpha1 gene. The
hemoglobin (Hb) was unequivocally detected by the isopropanol stability test and
confirmed as hyperunstable by mass spectrometry (MS) of the precipitate and
lysate, which showed proportions of 55% and 2.5% of alpha chains, respectively.
The instability appears to be driven by perturbation of globin-heme, and possibly
alpha1beta1 subunit, interactions.
PMID- 28696844
TI - Comparison of MicroRNAs Mediated in Reactivation of the gamma-Globin in beta
Thalassemia Patients, Responders and Non-Responders to Hydroxyurea.
AB - Drug induction of Hb F seems to be an ideal therapy for patients with hemoglobin
(Hb) disorders, and many efforts have been made to reveal the mechanism behind
it. Thus, we examined in vivo expression of some microRNAs (miRNAs) that are
thought to be involved in this process. Among beta-thalassemia (beta-thal)
patients who were undergoing hydroxyurea (HU) therapy in the past 3 months and
five healthy individuals, five responders and five non-responders, were also
included in the study. Erythroid progenitors were isolated by magnetic activated
cell sorting (MACS) and miRNA expression analyzed using reverse transcription
polymerase chain reaction (RT-PCR). We showed that gamma-globin, miR-210 and miR
486-3p had higher levels in the responders than the non-responders group.
Moreover, miR-150 and miR-320 had higher levels in the healthy group than both
non-responders and responders groups, but the expression of miR-96 did not show
any significant difference between the study groups. To the best of our
knowledge, this is the first study proposing that 'induction of cellular hypoxic
condition by Hb F inducing agents' could be the milestone of possible mechanisms
that explain why responders are able to reactivate gamma-globin genes and
subsequently, more production of Hb F, in response to these agents in comparison
to non-responders. However, further investigations need to be performed to verify
this hypothesis.
PMID- 28696845
TI - Decompensated Cirrhosis and Sickle Cell Disease: Case Reports and Review of the
Literature.
AB - Although its prevalence is unknown, liver involvement by sickle cell disease is
not uncommon and encompasses different clinical spectra including non cholestatic
and cholestatic disorders. Few data have been provided on chronic sickle cell
intrahepatic cholestasis (SCIC) clinical course, although cirrhosis has been
reported in sickle cell disease. However, no effective therapeutic approaches
have been recognized either to prevent or treat this condition. Here we present
two cases of adult sickle cell disease patients with decompensated cirrhosis.
Their liver biopsies showed sickle cell thrombi within the hepatic sinusoids.
Despite erythroexchange (EEX) transfusions, both patients suffered from major
sickle cell disease-related events, suggesting that EEX transfusions may not be
enough to impact on advanced liver involvement by sickle cell disease.
PMID- 28696847
TI - Invited Commentary: An Interventionist's Guide to Venous Sampling in
Endocrinopathies.
PMID- 28696848
TI - An Interventionist's Guide to Endocrine Consultations.
AB - Endocrinopathies are a heterogeneous group of disorders often resulting from
pathologic sources of hormone production. When the clinical scenario, laboratory
testing, and noninvasive imaging fail to aid confident identification of the
source of hormone excess, endocrine venous sampling may localize obscure lesions
to guide subsequent treatment. Knowledge of basic hormone signaling pathways,
common pathophysiologic disruptions of these pathways, and serologic evaluation
fosters informed conversations with referring physicians and effective patient
selection. Success in the angiography suite requires familiarity with normal and
variant anatomy of the multiple organs of the endocrine system, patient
preparation, stimulation and sampling techniques, specimen handling, and results
interpretation. (c)RSNA, 2017.
PMID- 28696849
TI - Retrievable IVC Filters: Comprehensive Review of Device-related Complications and
Advanced Retrieval Techniques.
AB - Use of retrievable inferior vena cava filters (RIVCFs) has grown exponentially
since their introduction into clinical practice, but many of these devices are
not retrieved. Some are not retrieved due to poor clinical follow-up, but other
devices remain in situ for extended periods because they present significant
technical challenges during retrieval. Because of these and other factors, many
of these devices were thus left in place permanently. However, recent data have
placed a renewed emphasis on device retrieval due to increased risk of RIVCF
related complications, which are positively correlated with filter dwell time.
Development of advanced filter retrieval techniques has had a significant impact
on the removal of embedded RIVCFs, permitting retrieval of the majority of
devices. The purpose of this article is to present an imaging and data review of
the dominant device-related factors that complicate RIVCF retrieval and to
describe the relevant advanced retrieval techniques to manage these factors.
RIVCF imaging is frequently encountered in daily clinical practice via various
imaging modalities. Therefore, diagnostic radiologists can play a vital role in
identifying filter-related issues. Familiarity with the context for managing
these issues in the interventional suite is essential for improving triage and
care of patients with RIVCFs. (c) RSNA, 2017.
PMID- 28696850
TI - Advanced MR Imaging Techniques for Differentiation of Neuropathic Arthropathy and
Osteomyelitis in the Diabetic Foot.
AB - Diagnosis and treatment of foot disease in patients with diabetes is a common
clinical-radiologic challenge, particularly the differentiation of neuropathic
arthropathy from osteomyelitis. Conventional clinical tests and imaging
techniques have limited accuracy for evaluation of the diabetic foot. The
introduction of morphologic magnetic resonance (MR) imaging in these patients has
provided a qualitative leap in diagnosis. The characteristics of soft-tissue and
bone marrow edema and their patterns of distribution throughout the foot allow
discrimination between both entities. However, in certain scenarios, the
application of MR imaging to this problem is limited because of overlapping
features between the two and the coexistence of infection and neuropathic
changes. Recent technical advances in MR imaging sequences have increased the
capability to add functional quantitative information to structural information.
Diffusion-weighted imaging is useful to determine the presence and extension of
osteomyelitis. Dynamic contrast-enhanced MR imaging may help to detect
differences between the vascularization patterns of neuropathic arthropathy and
osteomyelitis. MR angiography (with or without contrast material) is used in
clinical practice to identify candidate distal vessels for revascularization. MR
neurography, and especially diffusion-tensor imaging, provides quantitative
information about neural damage. These new sequences may help in assessment of
the different pathophysiologic conditions that occur in the diabetic foot. The
physical basis of these techniques, their limitations, and their potential
applications for diabetic foot assessment are detailed in this article. The
introduction of advanced MR imaging multiparametric protocols, with the aim of
enhancing the overall diagnostic accuracy of MR imaging, may help in treatment
decision making and lead to improved patient outcomes. (c) RSNA, 2017.
PMID- 28696852
TI - Imaging of Pregnancy-related Vascular Complications.
AB - Pregnancy results in substantial hemodynamic and prothrombotic changes that form
the foundation for downstream vascular complications, both during pregnancy and
in the postpartum period. In addition, several important risk factors, including
older patient age, diabetes, and smoking, can increase the risk for vascular
related pregnancy complications. Because radiologists often play an important
role in evaluation of the pregnant patient, understanding the pathophysiology of
vascular-related complications in pregnancy and their imaging appearances is
essential for diagnostic accuracy. The authors review relevant normal physiologic
changes of pregnancy, pathophysiologic changes, and imaging features of vascular
conditions that can manifest in conjunction with pregnancy. Particular attention
is given to pertinent imaging information that radiologists should provide to
referring clinicians to optimally affect the management of pregnant patients as
well as women in the peripartum and postpartum stages. Among the complications
discussed are preeclampsia; hemolysis, elevated liver enzymes, and low platelet
count (HELLP) syndrome; spontaneous coronary artery dissection; placental
abruption; amniotic fluid embolism and acute pulmonary embolism; dural venous
sinus thrombosis; ovarian vein thrombophlebitis; vasa previa; uterine
arteriovenous malformations; heritable aortopathies; and hereditary hemorrhagic
telangiectasia. To help radiologists avoid the use of unnecessary ionizing
radiation in pregnancy, imaging examination selection and optimization are also
reviewed. Radiologists should be familiar with the physiologic changes of
pregnancy, radiation risks during gestation, and pregnancy-related vascular
complications to improve imaging examination selection, diagnosis, and clinical
management. (c)RSNA, 2017.
PMID- 28696851
TI - US Evaluation of Juvenile Idiopathic Arthritis and Osteoarticular Infection.
AB - Juvenile idiopathic arthritis (JIA) and osteoarticular infection can cause
nonspecific articular and periarticular complaints in children. Although contrast
material-enhanced magnetic resonance imaging is the reference standard imaging
modality, musculoskeletal ultrasonography (US) is emerging as an important
adjunct imaging modality that can provide valuable information relatively quickly
without use of radiation or the need for sedation. However, diagnostic accuracy
requires a systemic approach, familiarity with various US techniques, and an
understanding of maturation-related changes. Specifically, the use of dynamic,
Doppler, and/or multifocal US assessments can help confirm sites of disease,
monitor therapy response, and guide interventions. In patients with JIA, ongoing
synovial inflammation can lead to articular and periarticular changes, including
synovitis, tenosynovitis, cartilage damage, bone changes, and enthesopathy.
Although these findings can manifest in adult patients with rheumatoid arthritis,
important differences and pitfalls exist because of the unique changes associated
with an immature and maturing skeleton. In patients who are clinically suspected
of having osteoarticular infection, the inability of US to evaluate the bone
marrow decreases its sensitivity. Therefore, the US findings should be
interpreted with caution because juxtacortical inflammation is suggestive, but
neither sensitive nor specific, for underlying osteomyelitis. Similarly, the
absence of a joint effusion makes septic arthritis extremely unlikely but not
impossible. US findings of JIA and osteoarticular infection often overlap.
Although certain clinical scenarios, laboratory findings, and imaging appearances
can favor one diagnosis over the other, fluid analysis may still be required for
definitive diagnosis and optimal treatment. US is the preferred modality for
fluid aspiration and administering intra-articular corticosteroid therapy. (c)
RSNA, 2017.
PMID- 28696853
TI - RSNA Diagnosis Live: A Novel Web-based Audience Response Tool to Promote Evidence
based Learning.
AB - Audience response systems have become more commonplace in radiology residency
programs in the last 10 years, as a means to engage learners and promote improved
learning and retention. A variety of systems are currently in use. RSNA Diagnosis
LiveTM provides unique features that are innovative, particularly for radiology
resident education. One specific example is the ability to annotate questions
with subspecialty tags, which allows resident performance to be tracked over
time. In addition, deficiencies in learning can be monitored for each trainee and
analytics can be provided, allowing documentation of resident performance
improvement. Finally, automated feedback is given not only to the instructor, but
also to the trainee. Online supplemental material is available for this article.
(c) RSNA, 2017.
PMID- 28696854
TI - CT Angiography in the Emergency Department: Maximizing Contrast Enhancement and
Image Quality While Minimizing Radiation Dose and Contrast Material Volume:
Vascular/Interventional Radiology.
PMID- 28696855
TI - Don't Forget the Abdominal Wall: Imaging Spectrum of Abdominal Wall Injuries
after Nonpenetrating Trauma.
AB - Abdominal wall injuries occur in nearly one of 10 patients coming to the
emergency department after nonpenetrating trauma. Injuries range from minor, such
as abdominal wall contusion, to severe, such as abdominal wall rupture with
evisceration of abdominal contents. Examples of specific injuries that can be
detected at cross-sectional imaging include abdominal muscle strain, tear, or
hematoma, including rectus sheath hematoma (RSH); traumatic abdominal wall hernia
(TAWH); and Morel-Lavallee lesion (MLL) (closed degloving injury). These injuries
are often overlooked clinically because of (a) a lack of findings at physical
examination or (b) distraction by more-severe associated injuries. However, these
injuries are important to detect because they are highly associated with
potentially grave visceral and vascular injuries, such as aortic injury, and
because their detection can lead to the diagnosis of these more clinically
important grave traumatic injuries. Failure to make a timely diagnosis can result
in delayed complications, such as bowel hernia with potential for obstruction or
strangulation, or misdiagnosis of an abdominal wall neoplasm. Groin injuries,
such as athletic pubalgia, and inferior costochondral injuries should also be
considered in patients with abdominal pain after nonpenetrating trauma, because
these conditions may manifest with referred abdominal pain and are often included
within the field of view at cross-sectional abdominal imaging. Radiologists must
recognize and report acute abdominal wall injuries and their associated intra
abdominal pathologic conditions to allow appropriate and timely treatment. (c)
RSNA, 2017.
PMID- 28696856
TI - Internal Thoracic Lymphadenopathy in Breast Cancer.
AB - The internal thoracic (IT) nodal basin is a first-echelon drainage pathway in the
breast, accounting for up to a quarter of its lymphatic drainage, primarily from
the deep structures of the breast. The presence of internal thoracic node (ITN)
metastases upstages the breast cancer (BC) patient to a minimum of clinical stage
III disease. Medial tumors, deep tumors, young age, axillary nodal metastases,
tumors of a high nuclear grade, lymphovascular invasion, and triple-negative
hormone receptor status are predisposing factors for ITN metastases from primary
BC. It has been observed that medial tumors carry a worse prognosis than lateral
tumors when all other factors are equal, indicating that understaging of ITN has
a significant impact on patient outcomes. Despite the established prognostic
significance of IT adenopathy in BC, this nodal basin is not routinely staged due
to the difficulty in accessing it and due to the controversy regarding its
management. Since the initial ITN studies in the 1960s, improvement in imaging
techniques and the availability of minimally invasive biopsy techniques have
fueled renewed interest in ITNs and their clinical significance in BC.
Radiologists who image and diagnose BC can offer more accurate staging
assessments by consistently evaluating the IT nodal chain in the BC patient. In
this article, the authors discuss current knowledge of the ITNs in BC and review
ITN anatomy. The imaging appearance of pathologic ITNs using various modalities,
potential mimics of IT adenopathy, and image-guided sampling techniques are
described. A succinct discussion of the clinical management of ITN-positive BC
and its challenges is also included. (c) RSNA, 2017.
PMID- 28696857
TI - Use of Radiology Procedure Codes in Health Care: The Need for Standardization and
Structure.
AB - Radiology procedure codes are a fundamental part of most radiology workflows,
such as ordering, scheduling, billing, and image interpretation. Nonstandardized
unstructured procedure codes have typically been used in radiology departments.
Such codes may be sufficient for specific purposes, but they offer limited
support for interoperability. As radiology workflows and the various forms of
clinical data exchange have become more sophisticated, the need for more advanced
interoperability with use of standardized structured codes has increased. For
example, structured codes facilitate the automated identification of relevant
prior imaging studies and the collection of data for radiation dose tracking. The
authors review the role of imaging procedure codes in radiology departments and
across the health care enterprise. Standards for radiology procedure coding are
described, and the mechanisms of structured coding systems are reviewed. In
particular, the structure of the RadLexTM Playbook coding system and examples of
the use of this system are described. Harmonization of the RadLex Playbook system
with the Logical Observation Identifiers Names and Codes standard, which is
currently in progress, also is described. The benefits and challenges of adopting
standardized codes-especially the difficulties in mapping local codes to
standardized codes-are reviewed. Tools and strategies for mitigating these
challenges, including the use of billing codes as an intermediate step in
mapping, also are reviewed. In addition, the authors describe how to use the
RadLex Playbook Web service application programming interface for partial
automation of code mapping. (c) RSNA, 2017.
PMID- 28696858
TI - Enhancing the Science of Discovery in Public Health Systems and Services Research
Through Participatory Research Methods.
AB - The objective was to combine cost analysis and participatory research to identify
actionable cost-saving opportunities in public health services for sexually
transmitted infections (STI). This study used a mixed-methods approach of
analyzing Florida public health data, combined with participatory research
approaches to data collection including quantitative web-based surveys,
qualitative in-depth interviews, and group discussions. Florida surveillance and
administrative data on STIs and county health department (CHD) costs of services
for 2012 were analyzed in addition to primary data collected from all Florida
CHDs during 2014 and 2015. Variations in STI service delivery practices were the
primary variables of concern. Variations in practices, rather than demographic
factors such as size of county or STI rates, were associated with variations in
cost. Five identified variations in practices were rated for cost savings, no or
minimal adverse health impact, and ease of implementation. Following discussion
of the ratings by CHDs, texting STI test results was ranked highest for quality
improvement implementation initiatives. This study provides a compelling example
of how in-depth qualitative and quantitative follow-up research focused on
discovery and development with the practice community provides critical insights
for interpreting administrative data and drawing accurate reality-based
conclusions. The research design was intended to be a highly adaptive research
approach that adjusts to the political and technical circumstances of delivering
public health services. The extensive stakeholder engagement throughout all
phases the study enables this research to address and overcome potential barriers
and challenges to actionable findings.
PMID- 28696860
TI - "Si Dios Quiere": Fatalismo and use of mental health services among Latinos with
a history of depression.
AB - Latinos are less likely to seek professional mental health care than other groups
in the United States. While fatalismo has long been hypothesized to be
responsible for this behavior, there is little evidence on this assumption. Using
an adapted version of the Behavioral Model of Health Service Use (BMHSU), and a
nationally representative sample, this study examined the association between
fatalismo and mental health service use among Latinos with a history of
depression. Participants (n = 703) were drawn from the 2007 Pew Hispanic
Healthcare survey. Results showed that fatalismo was significantly associated
with the use of psychiatric care, even after controlling for traditional
deterrents of health care access and utilization. The findings underscore the
importance of fatalismo in predicting Latinos' use of psychiatric care.
Implications for practice are discussed.
PMID- 28696859
TI - Nucleoporins redistribute inside the nucleus after cell cycle arrest induced by
histone deacetylases inhibition.
AB - Nucleoporins are the main components of the nuclear-pore complex (NPC) and were
initially considered as mere structural elements embedded in the nuclear
envelope, being responsible for nucleocytoplasmic transport. Nevertheless,
several recent scientific reports have revealed that some nucleoporins
participate in nuclear processes such as transcription, replication, DNA repair
and chromosome segregation. Thus, the interaction of NPCs with chromatin could
modulate the distribution of chromosome territories relying on the epigenetic
state of DNA. In particular, the nuclear basket proteins Tpr and Nup153, and the
FG-nucleoporin Nup98 seem to play key roles in all these novel functions. In this
work, histone deacetylase inhibitors (HDACi) were used to induce a
hyperacetylated state of chromatin and the behavior of the mentioned nucleoporins
was studied. Our results show that, after HDACi treatment, Tpr, Nup153 and Nup98
are translocated from the nuclear pore toward the interior of the cell nucleus,
accumulating as intranuclear nucleoporin clusters. These transitory structures
are highly dynamic, and are mainly present in the population of cells arrested at
the G0/G1 phase of the cell cycle. Our results indicate that the redistribution
of these nucleoporins from the nuclear envelope to the nuclear interior may be
implicated in the early events of cell cycle initialization, particularly during
the G1 phase transition.
PMID- 28696863
TI - Update on oral immunotherapy for egg allergy.
AB - Oral immunotherapy (OIT) is an emerging treatment of IgE-mediated egg allergy. In
the past decade, a multitude of studies have assessed the potential for egg OIT
to induce clinical desensitization. The following review will evaluate the
efficacy and safety of this therapy as determined by randomized controlled, non
randomized controlled and uncontrolled trials. Recent studies using reduced
allergenic egg products and anti-IgE assisted therapy to improve egg OIT safety
will also be discussed. Recent advances in the mechanisms underlying food OIT
suggest that certain immune parameters may be helpful in monitoring response to
therapy, including egg OIT. Although, egg OIT is consistently shown to be
effective with regards to clinical desensitization, fewer studies have looked at
persistent tolerance or sustained unresponsiveness. Limited results of long-term
follow-up trials suggest that this therapy may have disease-modifying effects. In
general, the comparison of studies is complicated by major differences in study
designs, OIT protocols and endpoints.
PMID- 28696868
TI - Challenges of Cardiac Transplantation Following the Fontan Procedure.
PMID- 28696869
TI - Feasibility of Biventricular Repair in Right Dominant Unbalanced Atrioventricular
Septal Defect: A New Echocardiographic Metric to Refine Surgical Decision-Making.
AB - BACKGROUND: Unbalanced forms of atrioventricular septal defect continue to be
challenging and present poor surgical outcomes. Echocardiographic indicators such
as atrioventricular valve index, right ventricle/left ventricle inflow angle, and
size of the ventricular septal defect have been identified as relevant
discriminators that may guide surgical strategy. Our purpose is to describe
another metric to refine surgical decision-making. METHODS: We outline a
geometrical description of the anatomic features of atrioventricular septal
defect and describe equations that help explain the interplay between the main
echocardiographic variables. RESULTS: A new metric called "indexed ventricular
septal defect" is defined as the size of the defect in relation to the valve
diameter. We derive a final equation relating this index with the
atrioventricular valve index and the right ventricle/left ventricle inflow angle.
In the light of that equation, we discuss the interdependence of variables and
employ data from a Congenital Heart Surgeons' Society study to set the limits of
the new index. CONCLUSION: Combined use of indexed ventricular septal defect and
atrioventricular valve index might help clarify surgical decision-making in
patients with mild and moderate unbalance (modified atrioventricular valve index
between 0.2 and 0.39). For indexed ventricular septal defect smaller than 0.2,
biventricular repair may be recommended. Between 0.2 and 0.35, this strategy
could probably be achieved depending on other factors. However, other strategies
should be considered for those patients showing an indexed ventricular septal
defect between 0.35 and 0.5. For values above 0.5 to 0.55, univentricular
palliation might be a reasonable strategy.
PMID- 28696870
TI - Seeing Through the Lies: Surgical Innovation and the Need for Transparency.
AB - The Robert E Gross Lecture was delivered by Professor Martin Elliott of London,
at Boston Children's Hospital June 1st, 2016. Professor Elliott makes a plea for
revision to the system of medical publication and academic reward, especially in
the field of surgery.
PMID- 28696871
TI - Anomalous Origin of Pulmonary Artery From Aorta: Neonatal Autologous
Aortopulmonary Reconstruction.
AB - Anomalous origin of a branch pulmonary artery (PA) from the ascending aorta is
rather rare within the spectrum of congenital cardiovascular anomalies. In the
scarce subset of patients with anomalous origin of right PA (RPA) from the
ascending aorta originating from the lateral aspect of the distal ascending
aorta, early neonatal repair by employing native aortic tissue for RPA
reconstruction combined with translocation of the aorta posteriorly to the RPA
can be an alternative option in the surgical armamentarium.
PMID- 28696872
TI - Anomalous Aortic Origin of a Coronary Artery: Symptoms Do Not Correlate With
Intramural Length or Ostial Diameter.
AB - BACKGROUND: Anomalous aortic origin of a coronary artery (AAOCA) is a known cause
of sudden death. Our hypothesis was that longer intramural length and smaller
ostial diameter correlate with preoperative symptoms. If true, this would assist
in the decision for surgical indications. We also assessed the accuracy of
preoperative imaging to predict intramural length. METHODS: Retrospective
analysis of patients who underwent AAOCA unroofing from 2006 to 2014. Patients
had preoperative computed tomography angiography (CTA) or magnetic resonance
imaging (MRI). Intramural length was measured. Intramural lengths and ostial
diameters were also measured intraoperatively (operating room [OR]). Symptoms
were noted. Intramural lengths and ostial diameters were compared between
patients with and without preoperative symptoms. The accuracy of intramural
length measured by CTA/MRI versus the length measured in the OR was assessed
using a Bland-Altman analysis. RESULTS: Sixty-six patients underwent surgical
repair of AAOCA. Fifty-two (79%) patients were symptomatic and 14 (21%) were
asymptomatic. Mean age was 12.4 +/- 4.0 years. There was no mortality. There was
strong agreement between intramural length measured by CTA/MRI and measured in
the OR. There was no significant difference in AAOCA intramural length in the
symptomatic (8.6 +/- 3.5 mm) and asymptomatic (8.9 +/- 2.8 mm, P = .77) patients,
which were measured both by CTA/MRI and intraoperatively (symptomatic 7.3 +/- 2.5
mm, asymptomatic 6.9 +/- 2.8 mm; P = .62). There was also no significant
difference in AAOCA ostial diameters between groups (symptomatic = 1.9 +/- 0.5
mm, asymptomatic = 1.6 +/- 0.5 mm; P = .09). CONCLUSION: Preoperative CTA/MRI was
very accurate in predicting the length of surgical unroofing. There was no
demonstrable correlation between preoperative symptoms and intramural AAOCA
length or AAOCA ostial diameter.
PMID- 28696873
TI - Modified Aortic Uncrossing Procedure: A Novel Approach for Norwood Palliation of
Complex Univentricular Congenital Heart Disease With a Circumflex Aorta.
AB - The circumflex aorta is a rare type of true vascular ring anomaly. It consists of
a retroesophageal right aortic arch, a left-sided descending thoracic aorta, and
a left-sided ligamentum arteriosum. The "aortic uncrossing procedure" described
by Planche and Lacour-Gayet is the procedure of choice for managing this aortic
anomaly in patients with a biventricular heart. The presence of a circumflex
aorta in a patient with heterotaxy syndrome and univentricular congenital heart
disease requiring Norwood palliation is highly unusual. We report such a case and
describe our approach to its surgical management.
PMID- 28696874
TI - Surgical Options for Uhl's Anomaly.
AB - BACKGROUND: Uhl's anomaly is an extremely rare congenital heart defect
characterized by a near total absence of the myocardium of the parietal wall of
the right ventricle. Few reports of surgical management exist in literature. We
present three patients with this anomaly who were managed with different surgical
strategies. PATIENTS AND METHODS: Patient 1: This 43-month-old girl had maternal
rubella syndrome with speech and hearing deficits and gross right heart failure.
Diagnosis was made on echocardiography and magnetic resonance imaging. She
underwent partial excision and plication of the right ventricular parietal wall
and total cavopulmonary connection. Patient 2: This 19-month-old boy presented
with progressive cyanosis and features of right heart failure. Diagnosis was
confirmed on echocardiography. He underwent right ventricular exclusion by
tricuspid valve closure and free wall plication followed by a bidirectional Glenn
procedure. Patient 3: This 21-year-old male presented with right heart failure
and cyanosis. Diagnosis was established with transesophageal echocardiography and
magnetic resonance imaging. As the hemodynamics were not suitable for a Fontan
conversion, a one and a half ventricle repair was done along with plication of
the right ventricular free wall and tricuspid valve annuloplasty. RESULTS: All
three patients were extubated within 24 hours. Patients 2 and 3 were discharged
relatively uneventfully, whereas patient 1 had a more prolonged stay due to
transient hepatic failure. All were symptomatically and clinically improved on
short-term follow-up. CONCLUSION: Uhl's anomaly is an extremely rare condition
with varied clinical presentation. Surgical exclusion of the right ventricle
yields gratifying results; however, surgical technique has to be adapted to the
individual patient.
PMID- 28696875
TI - Status and Challenges of Care in Africa for Adults With Congenital Heart Defects.
AB - The 54 countries in Africa have an estimated total annual congenital heart defect
(CHD) birth prevalence of 300,486 cases. More than half (51.4%) of the
continental birth prevalence occurs in only seven countries. Congenital heart
disease remains primarily a pediatric health issue in Africa because of the
deficient health-care systems: the adults with CHD made up just 10% of patients
with CHD in Ghana, and 13.7% of patients with CHD presenting for surgery in
Mozambique. With Africa's population projected to double in the next 35 years,
the already deficient health systems for CHD care will suffer unbearable strain
unless determined and courageous action is undertaken by the African leaders.
PMID- 28696876
TI - Experience Using Kaolin-Impregnated Sponge to Minimize Perioperative Bleeding in
Norwood Operation.
AB - PURPOSE: A kaolin-impregnated hemostatic sponge (QuikClot) is reported to reduce
intraoperative blood loss in trauma and noncardiac surgery. The purpose of this
study was to assess if this sponge was effective for hemostasis during Norwood
operation. DESCRIPTION: We conducted a retrospective review of patients
undergoing Norwood operation in infancy between 2011 and 2016 at our institution.
EVALUATION: Of 31 identified Norwood operations, a kaolin-impregnated sponge was
used intraoperatively in 15 (48%) patients. The preoperative profiles and
cardiopulmonary bypass status were similar between the operations with or without
kaolin-impregnated sponge. The comparison on each operative outcome between
operations with or without kaolin-impregnated sponge showed that the
intraoperative platelets, cryoprecipitate, and factor VII dosage were
significantly less in the operations with kaolin-impregnated sponge (55 mL, 10
mL, 0 ug/kg vs 72 mL, 15 mL, 45 ug/kg; P = .03, .021, .019), as well as the
incidence of perioperative bleeding complications (second cardiopulmonary bypass
for hemostasis or postoperative mediastinal exploration, 0% vs 31%, P = .043). A
logistic regression model showed that the nonuse of kaolin-impregnated sponge and
longer aortic cross clamp time were associated with perioperative bleeding
complication in univariable model ( P = .02 and .005). CONCLUSIONS: Use of kaolin
impregnated hemostatic sponge was associated with reduced blood product use and
perioperative bleeding complications in Norwood operation at a single
institution.
PMID- 28696877
TI - Multicenter Quality Improvement Project to Prevent Sternal Wound Infections in
Pediatric Cardiac Surgery Patients.
AB - BACKGROUND: Children undergoing cardiac surgery are at risk for sternal wound
infections (SWIs) leading to increased morbidity and mortality. Single-center
quality improvement (QI) initiatives have demonstrated decreased infection rates
utilizing a bundled approach. This multicenter project was designed to assess the
efficacy of a protocolized approach to decrease SWI. METHODS: Pediatric cardiac
programs joined a collaborative effort to prevent SWI. Programs implemented the
protocol, collected compliance data, and provided data points from local clinical
registries using Society of Thoracic Surgery Congenital Heart Surgery Database
harvest-compliant software or from other registries. RESULTS: Nine programs
prospectively collected compliance data on 4,198 children. Days between
infections were extended from 68.2 days (range: 25-82) to 130 days (range: 43
412). Protocol compliance increased from 76.7% (first quarter) to 91.3% (final
quarter). Ninety (1.9%) children developed an SWI preprotocol and 64 (1.5%)
postprotocol, P = .18. The 657 (15%) delayed sternal closure patients had a 5%
infection rate with 18 (5.7%) in year 1 and 14 (4.3%) in year 2 P = .43. Delayed
sternal closure patients demonstrated a trend toward increased risk for SWI of
1.046 for each day the sternum remained open, P = .067. Children who received
appropriately timed preop antibiotics developed less infections than those who
did not, 1.9% versus 4.1%, P = .007. CONCLUSION: A multicenter QI project to
reduce pediatric SWIs demonstrated an extension of days between infections and a
decrease in SWIs. Patients who received preop antibiotics on time had lower SWI
rates than those who did not.
PMID- 28696878
TI - Asynchronous Pumping of a Pulsatile Ventricular Assist Device in a Pediatric
Anastomosis Model.
AB - BACKGROUND: Both pulsatile and continuous flow ventricular assist devices are
being developed for pediatric congenital heart defect patients. Pulsatile devices
are often operated asynchronously with the heart in either an "automatic" or a
fixed beat rate mode. However, most studies have only investigated synchronized
ejection. METHODS: A previously validated viscoelastic blood solver is used to
investigate the parameters of pulsatility, power loss, and graft failure in a
pediatric aortic anastomosis model. RESULTS: Pulsatility was highest with
synchronized flow and lowest at a 90 degrees phase shift. Power loss decreased
at 90 degrees and 180 degrees phase shifts but increased at a 270 degrees
phase shift. Similar regions of potential intimal hyperplasia and graft failure
were seen in all cases but with phase-shifted ejection leading to higher wall
shear stress on the anastomotic floor and oscillatory shear index on the
anastomotic toe. CONCLUSION: The ranges of pulsatility and hemodynamics that can
result clinically using asynchronous pulsatile devices were investigated in a
pediatric anastomosis model. These results, along with the different
postoperative benefits of pump modulation, can be used to design an optimal
weaning protocol.
PMID- 28696879
TI - Outcomes of Patients Undergoing Primary Fontan Operation Beyond First Decade of
Life.
AB - OBJECTIVES: Studies on older patients undergoing primary Fontan operation (FO)
are limited, with conflicting results. We review our experience with these
patients beyond the first decade of life. PATIENTS AND METHODS: Between January
2000 and December 2014, a total of 105 patients >=10 years of age (mean 15.6 +/-
4.9, range 10-31, median 15 years) underwent primary FO without a prior
bidirectional superior cavopulmonary anastomosis (Bidirectional Glenn [BDG]).
Mean preoperative New York Heart Association (NYHA) class was 2.2 +/- 0.57.
RESULTS: Operative procedure was extra-cardiac FO in 62 patients (8 were
fenestrated). Forty-three had a lateral tunnel FO (26 were fenestrated). There
were 11 (10.5%) early deaths. Fourteen of the 94 early survivors experienced
prolonged pleural effusions, 7 had arrhythmias, and 2 had thromboembolic events.
Two patients underwent Fontan takedown. On univariate analysis, NYHA functional
class III, mean pulmonary artery (PA) pressure >=15 mm Hg, hematocrit >=60%,
preoperative ventricular dysfunction, and atrioventricular valve regurgitation
(AVVR) were associated with early mortality. Median follow-up was 78 (mean 88.9
+/- 6.3) months. In 94 survivors, 6 (6.4%) late deaths were encountered. At last
follow-up, 81 (86.2%) survivors were in NYHA class I. Actuarial survival was
84.7% +/- 3.7% at 5, 10, and 15 years. CONCLUSION: Carefully selected adolescents
and young adults can safely undergo the primary FO. However, persistent pleural
effusions, arrhythmias, thromboembolic events, and the need for reoperation
mandate regular follow-up in such patients. Preoperative NYHA functional class
III, mean PA pressure ? 15 mm Hg, hematocrit >= 60%, ventricular dysfunction, and
AVVR were associated with early mortality, suggesting that primary FO should be
avoided in such patients.
PMID- 28696880
TI - Performance of Pediatric Risk of Mortality Score Among Critically Ill Children
With Heart Disease.
AB - OBJECTIVE: To evaluate the performance of the Pediatric Risk of Mortality 3
(PRISM-3) score in critically ill children with heart disease. METHODS: Patients
<18 years of age admitted with cardiac diagnoses (cardiac medical and cardiac
surgical) to one of the participating pediatric intensive care units in the
Virtual Pediatric Systems, LLC, database were included. Performance of PRISM-3
was evaluated with discrimination and calibration measures among both cardiac
surgical and cardiac medical patients. RESULTS: The study population consisted of
87,993 patients, of which 49% were cardiac medical patients (n = 43,545) and 51%
were cardiac surgical patients (n = 44,448). The ability of PRISM-3 to
distinguish survivors from nonsurvivors was acceptable for the entire cohort (c
statistic 0.86). However, PRISM-3 did not perform as well when stratified by
varied severity of illness categories. Pediatric Risk of Mortality 3
underpredicted mortality among patients with lower severity of illness categories
(quintiles 1-4) whereas it overpredicted mortality among patients with greatest
severity of illness category (fifth quintile). When stratified by Society of
Thoracic Surgeons-European Association for Cardiothoracic Surgery (STS-EACTS)
categories, PRISM-3 overpredicted mortality among the STS-EACTS mortality
categories 1, 2, and 3 and underpredicted mortality among the STS-EACTS mortality
categories 4 and 5. Pediatric Risk of Mortality 3 overpredicted mortality among
centers with high cardiac surgery volume whereas it underpredicted mortality
among centers with low cardiac surgery volume. CONCLUSION: Data from this large
multicenter study do not support the use of PRISM-3 in cardiac surgical or
cardiac medical patients. In this study, the ability of PRISM-3 to distinguish
survivors from nonsurvivors was fair at best, and the accuracy with which it
predicted death was poor.
PMID- 28696881
TI - Persistent Left Superior Vena Cava: Incidence and Management in Patients
Undergoing Repair of Partial Anomalous Pulmonary Venous Connection.
AB - INTRODUCTION: A association between partial anomalous pulmonary venous connection
(PAPVC) and systemic venous anomalies has been described in the literature, but
the true incidence is yet to be elucidated. At our institution, we sought to find
the incidence of a persistent left superior vena cava (PLSVC) in patients
undergoing an operation for PAPVC. METHODS: A retrospective review of all
pediatric and adult patients with PAPVC who underwent surgical repair from
February 2006 to February 2016. All clinical, radiographic, and operative data
were reviewed. RESULTS: Eighty-five patients underwent surgical repair. A PLSVC
was identified in 15 (17.6%) patients. Every PLSVC drained/connected to the
coronary sinus. A bridging vein was present in only 26.7% (4 of 15).
Intraoperative management of the PLSVC consisted of direct cannulation in nine
(60%) patients, temporary occlusion in one (6.7%) patient, and ligation in one
(6.7%) patient. In the 15 PLSVC patients, 6 (40%) had a secundum atrial septal
defect (ASD), 2 (13.3%) had a patent foramen ovale (PFO), 10 (66.6%) had a sinus
venosus type defect, and 3 (20%) had both an ASD and sinus venosus-type defect.
Of the 15 patients with PAPVC and PLSVC, 14 (93%) had anomalous drainage of
pulmonary vein(s) on the right side, whereas 1 (7%) had veins on both sides with
anomalous drainage. CONCLUSION: Persistent left superior vena cava is present in
17.6% of patients undergoing an operation for PAPVC. Awareness of this
association as well as the intraoperative management of PLSVC is advised for
those that perform operations for PAPVC. As improper myocardial protection and
cardiopulmonary bypass strategies in the presence of a PLSVC can result in
deleterious outcomes.
PMID- 28696882
TI - Risk Factors for Mortality in Reoperations for Pediatric and Congenital Heart
Surgery in a Developing Country.
AB - BACKGROUND: The survival of patients with congenital heart disease has increased
in the recent years, because of enhanced diagnostic capabilities, better surgical
techniques, and improved perioperative care. Many patients will require
reoperation as part of staged procedures or to treat grafts deterioration and
residual or recurrent lesions. Reoperations favor the formation of cardiac
adhesions and consequently increase surgery time; however, the impact on
morbidity and operative mortality is certain. The objective of the study was to
describe the risk factors for mortality in pediatric patients undergoing a
reoperation for congenital heart disease. METHODS: Historic cohort of patients
who underwent reoperation after pediatric cardiac surgery from January 2009 to
December 2015. Operations with previous surgical approach different to sternotomy
were excluded from the analysis. RESULTS: In seven years, 3,086 surgeries were
performed, 481 were reoperations, and 238 patients fulfilled the inclusion
criteria. Mean number of prior surgeries was 1.4 +/- 0.6. Median age at the time
of reoperation was 6.4 years. The most common surgical procedures were staged
palliation for functionally univentricular heart (17.6%). Median cross-clamp time
was 66 minutes. Younger age at the moment of resternotomy, longer cross-clamp
time, and Society of Thoracic Surgeons-European Association for Cardio-Thoracic
Surgery Congenital Heart Surgery (STAT) Mortality Categories risk category
greater than three were risk factors for mortality. The number of resternotomies
was not associated with mortality. Mortality prior to hospital discharge was
4.6%, and mortality after discharge but prior to 30 days after surgery was 0.54%.
Operative mortality was 5.1%. CONCLUSIONS: Resternotomy in pediatric cardiac
surgery is a safe procedure in our center.
PMID- 28696883
TI - Decision-Making in Unbalanced Atrioventricular Septal Defect: Examining Another
Piece of the Puzzle.
PMID- 28696884
TI - Intra-Atrial Y-Graft Fontan for Univentricular Heart With Discontinuous Pulmonary
Arteries.
AB - The Y-graft Fontan as described today suffers from the disadvantage of being
hostage to restrictions imposed upon the design of the limbs of the Y by existent
cardiac anatomy. We describe a patient with discontinuous pulmonary arteries
following a prior Glenn shunt, who underwent Fontan completion using an intra
atrial Y-limb placement for recruitment of the discontinuous pulmonary artery.
Intracardiac placement of the limb(s) of the Y-graft could potentially increase
the applicability of this Fontan modification without being constrained by
external cardiac anatomy.
PMID- 28696894
TI - Preference of Aerosolized Pirfenidone to Oral Intake: An Experimental Model of
Pulmonary Fibrosis by Paraquat.
AB - BACKGROUND: Inhalation drug delivery is a fast, effective, and safe route of
delivering medication directly to the lungs. Thanks to the large surface area and
highly vascularized epithelium in lung, pulmonary drug delivery has been
considered as an effective route to deliver drugs to the systemic circulation.
Pirfenidone (PF), an oral antifibrotic agent, has been shown to slow down the
progression of the lung fibrosis. Inhalation or intrapulmonary delivery of PF
appears to be a good alternative to optimize drug delivery and minimize the
dosage, adverse and nonspecific effects. METHODS: Pulmonary fibrosis was induced
by paraquat in rats. After induction of fibrosis, PF was administered via oral
and inhalation routes for 14 consecutive days. The efficacy of oral and
inhalation routes were compared by evaluating morphological changes,
hydroxyproline content, tissue oxidative stress parameters, and proinflammatory
and profibrotic genes expression including transforming growth factor beta 1 (TGF
beta1), tumor necrosis factor alpha (TNF-alpha), tissue inhibitor of
metalloproteinase 1 (TIMP-1), and matrix metalloproteinase 2 (MMP-2) genes.
RESULTS: The results showed similar therapeutic effects and efficacy for both
inhalation and oral routes; however, the dose of inhalation route was much less
than that for oral administration. CONCLUSION: In conclusion, PF offers great
potential as an inhalation delivery formulation for treatment of pulmonary
fibrosis.
PMID- 28696895
TI - Urinary bladder cancer risk factors in an area of former coal, iron, and steel
industries in Germany.
AB - This study was performed to investigate the frequency of bladder cancer in
patients with an occupational history such as underground hard coal mining and/or
painting after the structural change in the local industry. A total of 206
patients with bladder cancer and 207 controls were enlisted regarding
occupational and nonoccupational bladder cancer risk factors by questionnaire.
The phase II enzymes N-acetyltransferase 2 (NAT2), glutathione S-transferases M1
(GSTM1), and T1 (GSTT1) and the single nucleotide polymorphism (SNP)
rs11892031[A/C] reported to be associated with bladder cancer in genome-wide
association studies were genotyped. The bladder cancer risk in varnishers and
underground hard coal miners was increased as previously shown in a study in this
area performed in the 1980s. The occupation of a car mechanic was associated with
a significantly elevated bladder cancer risk and higher in the case of
underground hard coal miners even though the mine was closed in 1987. The
frequency of GSTM1 negative genotype was comparable in cases and controls (53%
versus 54%). In the case of NAT2, the slow NAT2 genotype was more frequent (62%
versus 58%) and ultra-slow NAT2 genotype (NAT2*6A and/or *7B alleles only) was
23% versus 15%. An occupational history of a varnisher or an underground hard
coal miner remains a risk factor for bladder cancer occurrence. Data indicate
that in the case of bladder cancer, GSTM1 is a susceptibility factor related to
environmental and/or occupational exposure.
PMID- 28696896
TI - Assessment of DNA damage in a group of professional dancers during a 10-month
dancing season.
AB - Despite the numerous health benefits of physical activity, some studies reported
that increased intensity and duration may induce oxidative stress in several
cellular components including DNA. The aim of this study was to assess the level
of basal DNA damage as well as oxidative DNA damage in a group of professional
dancers before and after a 10-month dancing season. A group of individuals from
general population was also assessed as a control. The alkaline version of the
comet assay was the method selected to measure both basal DNA damage and
oxidative stress, since this method quantifies both endpoints. In order to
measure oxidative stress, the comet assay was coupled with a lesion-specific
endonuclease (formamidopyrimidine glycosylase) to detect oxidized purines. The
levels of oxidative DNA damage in dancers were significantly increased after the
dancing season. Pre-season levels of oxidative DNA damage were lower in dancers
than those obtained from the general population, suggesting an adaptation of
antioxidant system in dancers. Results of the present biomonitoring study
indicate the need for more effective measures to protect ballet dancers from
potentially occupational health risks related to regular intensive physical
exercise.
PMID- 28696897
TI - Polymorphisms of xenobiotic metabolizing enzymes in bladder cancer patients of
the Semmelweis University Budapest, Hungary.
AB - Polymorphic xenobiotic metabolizing enzymes such as N-acetyltransferase 2 (NAT2)
or glutathione S-transferase M1 (GSTM1) are known to modulate bladder cancer
risk. As no apparent data were available from Hungary, a former member of the
eastern European economic organization, a study was performed in Budapest. In
total, 182 bladder cancer cases and 78 cancer-free controls were investigated by
questionnaire. Genotypes of NAT2, GSTM1, GSTT1, rs1058396 and rs17674580 were
determined by standard methods. Current smokers' crude odds ratio (OR) (3.43) and
former smokers crude OR (2.36) displayed a significantly increased bladder cancer
risk. The risk rose by a factor of 1.56 per 10 pack years. Exposure to fumes was
associated with an elevated bladder cancer risk (23% cases, 13% controls). Sixty
four % of the cases and 59% of controls were slow NAT2 acetylators. It was not
possible to establish a particular impact of NAT2*6A and *7B genotypes (15 cases,
8%, 5 controls, 7%). GSTT1 exerted no marked influence on bladder cancer
(negative 21% cases vs. 22% controls). The portion of GSTM1 negative bladder
cancer patients was increased (63% cases vs. 54% controls). The SLC14A1 SNPs
rs1058396[AG/GG] and the nearby rs17674580[CT/TT] occurred more frequently in
cases (79% and 68%) than controls (77% and 55%). The portion of GSTM1 negative
bladder cancer patients is comparable with portions reported from other
industrialized areas like Lutherstadt Wittenberg/Germany (58%), Dortmund/Germany
(70%), Brescia/Italy (66%) or an occupational case-control series in Germany
(56%). Data indicate that GSTM1 is a susceptibility factor for environmentally
triggered bladder cancer rather than for smoking-mediated bladder cancer.
PMID- 28696905
TI - Protection during production: Problems due to prevention? Nail and skin condition
after prolonged wearing of occlusive gloves.
AB - Wearing of occlusive gloves during the whole working shift is considered a risk
factor for developing hand eczema, similar to wet work. Moreover, the increased
hydration due to glove occlusion may lead to brittle nails. Two hundred and
seventy clean room workers, wearing occlusive gloves for prolonged periods, and
135 administrative employees not using gloves were investigated. This included a
dermatological examination of the nails and the hands, using the Hand Eczema
ScoRe for Occupational Screening (HEROS), measurement of transepidermal water
loss (TEWL), and a standardized interview. Of the clean room workers, 39%, mainly
women, reported nail problems, mostly brittle nails with onychoschisis. Skin
score values showed no significant differences between HEROS values of both
groups. TEWL values of exposed subjects were similar to TEWL values of controls
40 min after taking off the occlusive gloves. In a multiple linear regression
analysis, male gender and duration of employment in the clean room were
associated with a significant increase in TEWL values. The effect of occlusion on
TEWL seems to be predominantly transient and not be indicative of a damaged skin
barrier. This study confirmed the results of a previous investigation showing no
serious adverse effect of wearing of occlusive gloves on skin condition without
exposure to additional hazardous substances. However, occlusion leads to softened
nails prone to mechanical injury. Therefore, specific prevention instructions are
required to pay attention to this side effect of occlusion.
PMID- 28696906
TI - Assessment of recent HIV testing among older adults in the United States.
AB - Older adults are the fastest growing segment of people living with HIV, and
unfortunately many are unaware of their HIV status. Many providers are reluctant
to ask older adults about their sexual histories, evaluate their risk factors,
and test for HIV, and older adults have low perception of HIV risk. Using data
from the 2013 to 2014 National Health and Nutrition Examination Survey, this
study assessed the prevalence of recent HIV testing among older adults in the
United States (n = 1,056) and identified predictors and barriers to recent HIV
testing. The prevalence of recent HIV testing was 28%. Recent HIV testing was
associated positively with male gender, education level, having public insurance,
having same sex sexual behavior, African, and Hispanic ethnicity, whereas age,
income-to-poverty ratio, and Asian ethnicity were associated negatively with
recent HIV testing. Public health social workers are advised that targeted HIV
testing for Asian, economically disadvantaged, female older adults is needed to
increase HIV awareness and detection and to decrease late diagnosis of HIV.
Provided public insurance was identified as a predictor of recent HIV testing,
facilitating economically disadvantaged older adults' eligibility for public
insurance that will likely improve access to HIV testing services and increase
HIV testing rates.
PMID- 28696908
TI - The Place of Culture and Religion in Patterns of Disclosure and Reporting Sexual
Abuse of Males: A Case Study of Ultra Orthodox Male Victims.
AB - This article deals with reporting patterns of sexual abuse in males in a
religious-cultural context through a case study of ultra-Orthodox Jewish (Haredi)
men who were young victims of sexual abuse. The study is based on in-depth
interviews with 40 Haredi men. The results indicate that sexual abuse involving
ultra-Orthodox boys was and is underreported. Moreover, the results indicate that
even when such incidents were reported, the avenues for disclosure were parents,
educational-religious figures, and friends. It was also found that silencing in
matters related to sexuality, viewing sexual abuse in boys as a serious sin and
taboo, and encouraging blind obedience-all of which characterize Haredi society
were factors in the underreporting. The results also show a strong tendency to
cover up incidents of sexual abuse on an individual level, on a family level, and
at the community level. The findings indicate a linkage between the religious and
cultural background of male victims of sexual abuse and their reporting patterns.
PMID- 28696907
TI - Child Sexual Abuse and HIV-Related Substance Use and Sexual Risk Across the Life
Course Among Males and Females.
AB - : Child sexual abuse is associated with substance use and sexual risk behaviors
during adolescence and adulthood, but no known studies have documented
associations across the life course in a nationally representative U.S. SAMPLE:
We used the National Longitudinal Study of Adolescent to Adult Health to measure
associations between child sexual abuse and substance use and sexual risk
behaviors during adolescence, young adulthood, and adulthood among males and
females (n = 11,820). Approximately 10% of females and 7% of males reported child
sexual abuse. Associations with substance use were strongest during adolescence
and lessened over time. Increased odds of sexual risk among those with a history
of child sexual abuse remained consistent through the life course. Significant
gender differences existed for some associations (e.g., adulthood multiple
partners: males adjusted odds ratio (AOR) = 1.73, 95%CI:1.18, 2.53; females AOR =
1.11, 95%CI:0.79, 1.56). Trauma-informed prevention interventions should address
child sexual abuse among both males and females to prevent substance use and
sexual risk behavior throughout the life course.
PMID- 28696909
TI - Increasing service user participation in local planning. A how-to manual for
macro practitioners, by J. M. Dunlop & M. J. Holosko.
PMID- 28696910
TI - The dynamic welfare state, by D. Stoesz.
PMID- 28696911
TI - N-acetyltransferase 1*10 genotype in bladder cancer patients.
AB - In a large bladder cancer study in the greater Berlin area with 425 cases and 343
controls, the haplotype N-acetyltransferase 1*10 (NAT1*10) was associated with a
decreased bladder cancer risk. In a recently published meta-analysis, results of
the studies were found to be inconclusive. Therefore, the aim of this study was
to investigate the frequency of NAT1*10 in bladder cancer patients and controls
recruited in an area without industries reported to be associated with increased
bladder cancer risk. Rs1057126 (1088 T > A) and rs15561 (1095 C > A) were
determined in 412 bladder cancer patients and 415 controls without a known
history of malignancies. With these two single-nucleotide polymorphisms (SNP), it
was possible to distinguish between NAT1*4 (wild type), NAT1*3 (1095 C > A), and
NAT1*10 (1088 T > A, 1095C > A). The frequencies of the determined NAT1
haplotypes did not differ markedly between cases and controls: NAT1*4: 74%,
NAT1*3: 6%, NAT1*10: 20%. Bladder cancer risk was not significantly modulated by
NAT1*10/*10 (OR 1.03, 95% CI 0.71-1.48) but was higher for NAT1*3/*3 genotypes
(OR 2.05, 95% CI 1.32-3.21). In contrast to the Berlin study from 2001, data in
present study demonstrated that NAT1*10 haplotype was not associated with a
significantly decreased bladder cancer risk. This may be due to local effects in
the greater Berlin area, particularly at the time of investigation. The findings
of the present study are in agreement with observations of a recently published
meta-analysis which also showed no relevant impact of NAT1*10 haplotype on
bladder cancer risk. The impact of the rare NAT1*3/*3 genotype was significant
but this may be attributed to rarity without major practical relevance.
PMID- 28696913
TI - Linking physiological parameters to perturbations in the human exposome:
Environmental exposures modify blood pressure and lung function via inflammatory
cytokine pathway.
AB - Human biomonitoring is an indispensable tool for evaluating the systemic effects
derived from external stressors including environmental pollutants, chemicals
from consumer products, and pharmaceuticals. The aim of this study was to explore
consequences of environmental exposures to diesel exhaust (DE) and ozone (O3) and
ultimately to interpret these parameters from the perspective of in vitro to in
vivo extrapolation. In particular, the objective was to use cytokine expression
at the cellular level as a biomarker for physiological systemic responses such as
blood pressure and lung function at the systemic level. The values obtained could
ultimately link in vivo behavior to simpler in vitro experiments where cytokines
are a measured parameter. Human exposures to combinations of DE and O3 and the
response correlations between forced exhaled volume in 1 second (FEV1), forced
vital capacity (FVC), systolic and diastolic blood pressure (SBP and DBP,
respectively), and 10 inflammatory cytokines in blood (interleukins 1beta, 2, 4,
5, 8, 10, 12p70 and 13, IFN-gamma, and TNF-alpha) were determined in 15 healthy
human volunteers. Results across all exposures revealed that certain individuals
displayed greater inflammatory responses compared to the group and, generally,
there was more between-person variation in the responses. Evidence indicates that
individuals are more stable within themselves and are more likely to exhibit
responses independent of one another. Data suggest that in vitro findings may
ultimately be implemented to elucidate underlying adverse outcome pathways (AOP)
for linking high-throughput toxicity tests to physiological in vivo responses.
Further, this investigation supports assessing subjects based upon individual
responses as a complement to standard longitudinal (pre vs. post) intervention
grouping strategies. Ultimately, it may become possible to predict a
physiological (systemic) response based upon cellular-level (in vitro)
observations.
PMID- 28696914
TI - Micro-brushing-based technique to gain fresh urothelial cells for gene expression
analysis.
AB - The gold standard of saving fresh tissue in liquid nitrogen has some serious
disadvantages in that this process is not available in daily medical routine
practices even in many tumor centers. Our approach of a new minimally invasive
technique is obtaining urothelial cells via micro-brushing the urinary bladder on
the occasion of urological routine methods such as transurethral resection (TUR).
Urothelial cells were obtained from 25 patients via two different micro-brushes
from tumor tissue and from macroscopically healthy tissue during TUR. These cells
were immediately transferred into RNA stabilization reagent and stored at -20
degrees C. Later, mRNA was isolated, transcribed into cDNA, and amplified. cDNA
was stored at -20 degrees C until analysis. The mean RNA quantity was 99.5 ng/MUl
from tumor tissues and 66.3 ng/MUl from macroscopically tumor-free tissue,
enabling a considerable number of analyses. The quality of the gained cDNA
allowed semi-quantitative PCR analysis of GSTM1 expression as well as
quantitative PCR analysis of c-Myc expression. The new technique presents several
important advantages. First, staging and grading of the stained tumor sample can
be examined immediately, whereas fresh frozen sample is not examined until some
days later. Further, this method can be applied in hospitals with no access to
liquid nitrogen or without capability to provide an additional examination of
frozen tumor sample by a pathologist. This presented minimally invasive method
enables investigation of gene expression in the urinary bladder without
disadvantages of the need for storage of fresh tissues in liquid nitrogen.
PMID- 28696918
TI - Gold nanorods induce early embryonic developmental delay and lethality in
zebrafish (Danio rerio).
AB - Due to their unique electronic and optical features, gold nanoparticles (AuNP)
have received a great deal of attention for application in different fields such
as catalysis, electronics, and biomedicine. The large-volume manufacturing
predicted for future decades and the inevitable release of these substances into
the environment necessitated an assessment of potential adverse human and
ecological risks due to exposure to AuNP. Accordingly, this study aimed to
examine the acute and developmental toxicity attributed to a commercial
suspension of Au nanorods stabilized with cetyltrimethylammonium bromide (CTAB
AuNR) using early embryonic stages of zebrafish (Danio rerio), a well-established
model in ecotoxicology. Zebrafish embryos were exposed to CTAB-AuNR (0-150 ug/L)
to determine for developmental assessment until 96 hr post fertilization (hpf)
and lethality. Uptake of CTAB-AuNR by embryos and nanoparticles potential to
induce DNA damage was also measured at 48 and 96 hpf. Analysis of the
concentration-response curves with cumulative mortality at 96 hpf revealed a
median lethal concentration (LC50,96h) of 110.2 MUg/L. At sublethal
concentrations, CTAB-AuNR suspensions were found to produce developmental
abnormalities such as tail deformities, pericardial edema, decreased body length,
and delayed eye, head, and tail elongation development. Further, less than 1% of
the initial concentration of CTAB-AuNR present in the exposure media was
internalized by zebrafish embryos prior to (48 hpf) and after hatching (96 hpf).
In addition, no marked DNA damage was detected in embryos after exposure to CTAB
AuNR. Overall, CTAB-AuNR suspensions produced lethal and sublethal effects on
zebrafish embryos with possible repercussions in fitness of adult stages.
However, these results foresee a low risk for fish since the observed effects
occurred at concentrations above the levels expected to find in the aquatic
environment.
PMID- 28696919
TI - Nomad scientists and the ones left behind.
AB - To improve the diversity of the scientific workforce, we should not penalize
researchers who are unable to move abroad for long periods.
PMID- 28696920
TI - Heads up on concussion in para sport.
PMID- 28696921
TI - ASPsiRNA: A Resource of ASP-siRNAs Having Therapeutic Potential for Human Genetic
Disorders and Algorithm for Prediction of Their Inhibitory Efficacy.
AB - Allele-specific siRNAs (ASP-siRNAs) have emerged as promising therapeutic
molecules owing to their selectivity to inhibit the mutant allele or associated
single-nucleotide polymorphisms (SNPs) sparing the expression of the wild-type
counterpart. Thus, a dedicated bioinformatics platform encompassing updated ASP
siRNAs and an algorithm for the prediction of their inhibitory efficacy will be
helpful in tackling currently intractable genetic disorders. In the present
study, we have developed the ASPsiRNA resource
(http://crdd.osdd.net/servers/aspsirna/) covering three components viz (i)
ASPsiDb, (ii) ASPsiPred, and (iii) analysis tools like ASP-siOffTar ASPsiDb is a
manually curated database harboring 4543 (including 422 chemically modified) ASP
siRNAs targeting 78 unique genes involved in 51 different diseases. It furnishes
comprehensive information from experimental studies on ASP-siRNAs along with
multidimensional genetic and clinical information for numerous mutations.
ASPsiPred is a two-layered algorithm to predict efficacy of ASP-siRNAs for fully
complementary mutant (Effmut) and wild-type allele (Effwild) with one mismatch by
ASPsiPredSVM and ASPsiPredmatrix , respectively. In ASPsiPredSVM, 922 unique ASP
siRNAs with experimentally validated quantitative Effmut were used. During 10
fold cross-validation (10nCV) employing various sequence features on the
training/testing dataset (T737), the best predictive model achieved a maximum
Pearson's correlation coefficient (PCC) of 0.71. Further, the accuracy of the
classifier to predict Effmut against novel genes was assessed by leave one target
out cross-validation approach (LOTOCV). ASPsiPredmatrix was constructed from rule
based studies describing the effect of single siRNA:mRNA mismatches on the
efficacy at 19 different locations of siRNA. Thus, ASPsiRNA encompasses the first
database, prediction algorithm, and off-target analysis tool that is expected to
accelerate research in the field of RNAi-based therapeutics for human genetic
diseases.
PMID- 28696922
TI - Functional Profiling of Transcription Factor Genes in Neurospora crassa.
AB - Regulation of gene expression by DNA-binding transcription factors is essential
for proper control of growth and development in all organisms. In this study, we
annotate and characterize growth and developmental phenotypes for transcription
factor genes in the model filamentous fungus Neurospora crassa We identified 312
transcription factor genes, corresponding to 3.2% of the protein coding genes in
the genome. The largest class was the fungal-specific Zn2Cys6 (C6) binuclear
cluster, with 135 members, followed by the highly conserved C2H2 zinc finger
group, with 61 genes. Viable knockout mutants were produced for 273 genes, and
complete growth and developmental phenotypic data are available for 242 strains,
with 64% possessing at least one defect. The most prominent defect observed was
in growth of basal hyphae (43% of mutants analyzed), followed by asexual
sporulation (38%), and the various stages of sexual development (19%). Two growth
or developmental defects were observed for 21% of the mutants, while 8% were
defective in all three major phenotypes tested. Analysis of available mRNA
expression data for a time course of sexual development revealed mutants with
sexual phenotypes that correlate with transcription factor transcript abundance
in wild type. Inspection of this data also implicated cryptic roles in sexual
development for several cotranscribed transcription factor genes that do not
produce a phenotype when mutated.
PMID- 28696923
TI - Whole Genome Sequence of the Heterozygous Clinical Isolate Candida krusei 81-B-5.
AB - Candida krusei is a diploid, heterozygous yeast that is an opportunistic fungal
pathogen in immunocompromised patients. This species also is utilized for
fermenting cocoa beans during chocolate production. One major concern in the
clinical setting is the innate resistance of this species to the most commonly
used antifungal drug fluconazole. Here, we report a high-quality genome sequence
and assembly for the first clinical isolate of C. krusei, strain 81-B-5, into 11
scaffolds generated with PacBio sequencing technology. Gene annotation and
comparative analysis revealed a unique profile of transporters that could play a
role in drug resistance or adaptation to different environments. In addition, we
show that, while 82% of the genome is highly heterozygous, a 2.0 Mb region of the
largest scaffold has undergone loss of heterozygosity. This genome will serve as
a reference for further genetic studies of this pathogen.
PMID- 28696924
TI - The SEK-1 p38 MAP Kinase Pathway Modulates Gq Signaling in Caenorhabditis
elegans.
AB - Gq is a heterotrimeric G protein that is widely expressed in neurons and
regulates neuronal activity. To identify pathways regulating neuronal Gq
signaling, we performed a forward genetic screen in Caenorhabditis elegans for
suppressors of activated Gq. One of the suppressors is an allele of sek-1, which
encodes a mitogen-activated protein kinase kinase (MAPKK) in the p38 MAPK
pathway. Here, we show that sek-1 mutants have a slow locomotion rate and that
sek-1 acts in acetylcholine neurons to modulate both locomotion rate and Gq
signaling. Furthermore, we find that sek-1 acts in mature neurons to modulate
locomotion. Using genetic and behavioral approaches, we demonstrate that other
components of the p38 MAPK pathway also play a positive role in modulating
locomotion and Gq signaling. Finally, we find that mutants in the SEK-1 p38 MAPK
pathway partially suppress an activated mutant of the sodium leak channel, NCA
1/NALCN, a downstream target of Gq signaling. Our results suggest that the SEK-1
p38 pathway may modulate the output of Gq signaling through NCA-1(unc-77).
PMID- 28696925
TI - Mouse Chromosome 4 Is Associated with the Baseline and Allergic IgE Phenotypes.
AB - Regulation of IgE concentration in the blood is a complex trait, with high
concentrations associated with parasitic infections as well as allergic diseases.
A/J strain mice have significantly higher plasma concentrations of IgE, both at
baseline and after ovalbumin antigen exposure, when compared to C57BL/6J strain
mice. Our objective was to determine the genomic regions associated with this
difference in phenotype. To achieve this, we used a panel of recombinant congenic
strains (RCS) derived from A/J and C57BL/6J strains. We measured IgE in the RCS
panel at baseline and following allergen exposure. Using marker by marker
analysis of the RCS genotype and phenotype data, we identified multiple regions
associated with the IgE phenotype. A single region was identified to be
associated with baseline IgE level, while multiple regions wereassociated with
the phenotype after allergen exposure. The most significant region was found on
Chromosome 4, from 81.46 to 86.17 Mbp. Chromosome 4 substitution strain mice had
significantly higher concentration of IgE than their background parental strain
mice, C57BL/6J. Our data presents multiple candidate regions associated with
plasma IgE concentration at baseline and following allergen exposure, with the
most significant one located on Chromosome 4.
PMID- 28696926
TI - Habitat Predicts Levels of Genetic Admixture in Saccharomyces cerevisiae.
AB - Genetic admixture can provide material for populations to adapt to local
environments, and this process has played a crucial role in the domestication of
plants and animals. The model yeast, Saccharomyces cerevisiae, has been
domesticated multiple times for the production of wine, sake, beer, and bread,
but the high rate of admixture between yeast lineages has so far been treated as
a complication for population genomic analysis. Here, we make use of the low
recombination rate at centromeres to investigate admixture in yeast using a
classic Bayesian approach and a locus-by-locus phylogenetic approach. Using both
approaches, we find that S. cerevisiae from stable oak woodland habitats are less
likely to show recent genetic admixture compared with those isolated from
transient habitats such as fruits, wine, or human infections. When woodland yeast
strains do show recent genetic admixture, the degree of admixture is lower than
in strains from other habitats. Furthermore, S. cerevisiae populations from oak
woodlands are genetically isolated from each other, with only occasional
migration between woodlands and local fruit habitats. Application of the
phylogenetic approach suggests that there is a previously undetected population
in North Africa that is the closest outgroup to the European S. cerevisiae,
including the domesticated Wine population. Careful testing for admixture in S.
cerevisiae leads to a better understanding of the underlying population structure
of the species and will be important for understanding the selective processes
underlying domestication in this economically important species.
PMID- 28696927
TI - Maternal smoking during pregnancy and offspring antisocial behaviour: findings
from a longitudinal investigation of discordant siblings.
AB - BACKGROUND: Although many observational studies have found a strong association
between maternal smoking during pregnancy (MSP) and offspring antisocial
behaviour, the likelihood that this relationship is causal remains unclear. To
comment on the potential causality of this association, the current investigation
used a between-within decomposition approach to examine the association between
MSP and multiple indices of adolescent and adult antisocial behaviour. METHODS:
Study participants were offspring of women enrolled in the Providence and Boston
sites of the Collaborative Perinatal Project. Information on MSP was collected
prospectively. Antisocial behaviour was assessed via self-report and through
official records searches. A subset of the adult offspring (average age: 39.6
years) were enrolled in a follow-up study oversampling families with multiple
siblings. Participants in this follow-up study self-reported on juvenile and
adult antisocial behaviours during a structured interview (n=1684). Official
records of juvenile (n=3447) and adult (n=3433) criminal behaviour were obtained
for participants in the Providence cohort. Statistical models allowed between
family effects of MSP exposure to differ from within-family effects. In the
absence of heterogeneity in between-family versus within-family estimates, a
combined estimate was calculated. RESULTS: MSP was associated with a range of
antisocial behaviours, measured by self-report and official records. For example,
MSP was associated with increased odds of elevated levels of antisocial
behaviours during adolescence and adulthood, as well as violent and non-violent
outcomes during both developmental periods. CONCLUSIONS: Findings are consistent
with a small-to-moderate causal effect of MSP on adolescent and adult antisocial
behaviour.
PMID- 28696928
TI - Spotlight on the July 11 issue.
PMID- 28696929
TI - The entire world.
PMID- 28696930
TI - Dramatic improvement of tardive dyskinesia movements by inline skating.
PMID- 28696931
TI - Editors' Note.
PMID- 28696932
TI - Letter re: Hand postures in primary and secondary generalized tonic-clonic
seizures.
PMID- 28696933
TI - Author response: Hand postures in primary and secondary generalized tonic-clonic
seizures.
PMID- 28696934
TI - Author update: Sarcoplasmic MxA expression: A valuable marker of dermatomyositis.
PMID- 28696935
TI - Revisiting neurofibromatosis type 2 diagnostic criteria to exclude LZTR1-related
schwannomatosis.
PMID- 28696936
TI - Autologous hematopoietic stem cell transplantation in multiple sclerosis: A meta
analysis.
PMID- 28696937
TI - Clinical Reasoning: A 54-year-old woman with dementia, myoclonus, and ataxia.
PMID- 28696938
TI - Teaching NeuroImages: Osteochondroma arising from the clavicle causing
ipsilateral Horner syndrome.
PMID- 28696939
TI - Teaching Video NeuroImages: Apraxia of eyelid closure following right hemispheric
infarction.
PMID- 28696940
TI - Multiple selective events at the PRDM16 functional pathway shaped adaptation of
western European populations to different climate conditions.
AB - Several studies highlighted the role of climate in shaping many human
evolutionary processes. This occurred even in relatively recent times, having
affected various human phenotypic traits, among which metabolic processes that
orchestrate absorption and accumulation of substances to maintain energy
homeostasis, that is critical for the survival of individuals in high energy
expenditure environments. To date, most researches have focalized on detection of
climatic influence on SNPs' frequency in populations exposed to extreme
environmental conditions or by comparing variation patterns between populations
from different continents. In this study, we instead explored the genetic
background of distinct western European human groups at loci involved in
nutritional and thermoregulation processes, to test whether patterns of
differential local adaptation to environmental conditions could be appreciated
also at a lower geographical scale. Taking advantage from the 1000 Genomes
Project data, genetic information for 21 genes involved in nutritional and
thermoregulation processes was analysed for three western European populations.
The applied Anthropological Genetics methods pointed to appreciable
differentiation between the examined groups especially for the PRDM16 gene.
Moreover, several neutrality tests suggested that balancing selection has acted
on different regions of the gene in people from Great Britain, as well as that
more recent positive selection could have also targeted some PRDM16 SNPs in Finn
and Italian populations. These series of adaptive footprints are plausibly
related to climate variability in both ancient and relatively recent times. Since
this locus is involved in thermoregulation mechanisms and adipogenesis, local
adaptations mediated by a pathway related to the brown adipose tissue activity
could have evolved in response to changing cold temperature exposures of such
populations.
PMID- 28696941
TI - Reflections on "race" in science and society in the United States.
PMID- 28696942
TI - Race and racism in France.
PMID- 28696943
TI - Reflections on "race" in science and society in Germany.
PMID- 28696946
TI - Optimal treatment for lumbar spinal stenosis: an update.
AB - PURPOSE OF REVIEW: Our review of current literature within the past 12-24 months
for the treatment of lumbar spinals stenosis (LSS) serves to update providers on
recent advances and comparisons regarding therapy spanning lifestyle
modification, pharmacologic therapy, minimally invasive interventions, and
surgical interventions. RECENT FINDINGS: Current literature supporting the
inclusion of physical therapy and gabapentin/pregabalin within an initial
treatment regimen have been positive. A recent randomized, double-blinded
clinical trial of adding calcitonin to epidural steroid injections have shown
improvement in pain and function up to 1 year. The minimally invasive lumbar
decompression (mild) procedure is showing ongoing beneficial results in pain and
function. Spinal cord stimulation (SCS) may have a role for select patients with
lumbar spinal stenosis. Finally, the benefits of surgical treatment versus
nonsurgical treatment is ultimately inconclusive because of the nature of data
collection, inconsistencies with the clinical definition of LSS, and a lack of
standardized treatment guidelines. SUMMARY: Our review of current research
demonstrates there is a positive role for the current conservative therapies,
with favorable results for interventions such as minimally invasive decompression
and SCS. Pharmacologic interventions such as systemic prostaglandin analogues and
epidural agents such as calcitonin demonstrate early promise, but need to undergo
additional safety testing and confirmatory trials. Further long-term research
with validated, objective measurements for the aforementioned treatments are
needed to draw any definitive conclusions for clinical practice.
PMID- 28696945
TI - Correction: The complex genetics of gait speed: genome-wide meta-analysis
approach.
PMID- 28696947
TI - Regional blocks carried out during general anesthesia or deep sedation: myths and
facts.
AB - PURPOSE OF REVIEW: More patients will accept regional blocks if these are
performed during sedation or general anesthesia. This review discusses regional
anesthesia in sedated or anesthetized patients. RECENT FINDINGS: As complications
of regional blocks are rare, regional anesthesia can be considered aswell
tolerated. Awake patients will notice only a minority of needle-to-nerve
contacts, that renders the notion of a 'live monitor' obsolete. Using high
resolution ultrasound, the needle can be advanced to an extraepineural position
for injection, thus strictly avoiding needle-to-nerve contact or intraepineural
injection of local anesthetic. Rare cases of intoxication manifest more
immediately when the patient is awake but some general anesthesia drugs reduce
the seizure-inducing potency of local anesthetics, and hemodynamic signs of
intoxication are also detectable under general anesthesia, allowing for faster
cardiopulmonary resuscitation as the patient is anesthetized already. SUMMARY:
With the use of ultrasound guidance in skilled hands, it is a reasonable option
to perform neuraxial and peripheral regional blocks in sedated or anesthetized
patients. Performing the procedure safely and effectively requires an adequate
level of experience with the specific block technique in question.
PMID- 28696948
TI - Design and Early Experience With a Real-World Surgical Registry.
AB - OBJECTIVES: We describe the rationale, design, and methods and 6-year experience
with a real-world surgical registry for female pelvic reconstructive and
incontinence procedures and postoperative outcomes. METHODS: The primary goal of
creating this registry was to establish the feasibility of prospective data
capture for all urogynecologic procedures. Data captured included baseline
demographics, surgical procedures, perioperative complications, and subjective
and objective findings up to 36 months after surgery. RESULTS: The Pelvic
Reconstruction and Incontinence Surgery +/- Mesh Registry was developed over 3
years to include 194 unique variables for prospective data capture. The registry
was implemented in December 2010, and data from 924 separate case events from a
single surgeon were recorded, comprising 100% surgical case capture. Cases
included a variety of procedures representing a comprehensive urogynecology
practice on 804 unique patients. Patients who were asked to participate in long
term follow-up (n = 299) returned with attendance of 96% at 6 weeks, 64% at 6
months, 51% at 12 months, 39% at 24 months, and 22% at 36 months. CONCLUSIONS:
The Pelvic Reconstruction and Incontinence Surgery +/- Mesh Registry effectively
captured all urogynecologic procedures for the purpose of quality improvement.
This real-world tool demonstrates that 100% case capture is feasible and provides
valuable information for the highly motivated surgeon, although adequate long
term follow-up is limited. Additional research is needed to better understand the
role of surgical registries for quality improvement and development of patient
centered strategies to increase long-term follow-up.
PMID- 28696949
TI - Procedure Choice in Primary Versus Recurrent Prolapse: A Study of Fellowship
Trained Surgeons.
AB - OBJECTIVE: This retrospective study describes procedures of choice in management
of patients with primary prolapse compared with recurrence prolapse patients by
fellowship-trained surgeons. METHODS: Surgically managed primary and recurrent
prolapse cases from 2012 to 2015 at Houston Methodist Hospital were reviewed.
Baseline characteristics, compartment defects, and stage were compared. Mean
interval from the index surgeries to management of prolapse recurrence was
recorded. In recurrence cases, mesh complaints were noted if present. Primary
outcome was the procedure type used to manage cases of recurrence and primary
prolapse. Logistic regression was used to determine odds ratio (OR) for the
procedure of choice in recurrence and primary repairs of prolapse. RESULTS: Of
386 cases reviewed, 379 met criteria for inclusion; 25.8% of repairs were for
recurrence. Recurrence patients were significantly older than primary cases
(mean, 63.6 vs 60.5; P = 0.03) and had been postmenopausal for longer (P =
0.004). Median time interval to surgical management of recurrence was 8 years.
Thirty percent of recurrence patients treated previously by mesh had mesh
complaints. There was no difference in the distribution of defects or stage.
Sacrocolpopexy was more frequently used to manage recurrent prolapse (OR, 2.6334;
P < 0.0005). Vaginal mesh repairs showed no difference in utilization.
Uterosacral ligament fixation (OR, 0.347; P = 0.002) was used more often in
primary prolapse. Anterior colporrhaphy (OR, 0.398; P = 0.0005) and uterosacral
ligament fixation (OR, 0.347; P = 0.002) were performed less in recurrence cases.
CONCLUSION: Fellowship-trained urogynecologists at this institution utilize
sacrocolpopexy mesh more frequently in recurrent prolapse, and uterosacral
ligament fixation was used more frequently in primary prolapse cases.
PMID- 28696951
TI - Postoperative Considerations Following Hip Arthroscopy.
PMID- 28696953
TI - Out of air: Is going to high altitude safe for your patient?
AB - As more people travel to high altitudes for recreation or work, more travelers
with underlying medical conditions will need advice before traveling or treatment
for altitude illness. This article focuses on the two main issues for travelers:
whether travel to a high altitude will have a negative effect on their underlying
medical condition and whether the medical condition increases the patient's risk
of developing altitude illness. Although patients with severe pulmonary or
cardiac conditions are most at risk in the hypoxic environment, other conditions
such as diabetes and pregnancy warrant attention as well.
PMID- 28696950
TI - The Role of Stigma and Denormalization in Suicide-Prevention Laws in East Asia: A
Sociocultural, Historical, and Ethical Perspective.
AB - In many Western countries, the criminalization and stigmatization of suicide has
given way to a biomedical approach aimed at destigmatizing suicide and treating
underlying mental illness. By contrast, in many East Asian countries, suicide has
never historically been criminalized or stigmatized. High rates of suicide in
Japan, South Korea, and Taiwan have recently led policy makers in those countries
to pursue innovative suicide-prevention strategies. The intentional
denormalization of harmful behaviors has been discussed in the public health and
ethics literatures, particularly with regard to smoking cessation, and could
represent a novel mechanism for preventing suicides in East Asia. Using examples
from the sociocultural, historical, and legal discourses surrounding suicide in
Western and East Asian contexts, we suggest that denormalization can be a
justified, culturally relevant suicide-prevention strategy, but that care must be
taken to avoid shaming or stigmatizing suicidal individuals. Specifically, we
propose the term weak denormalization to refer to an ethically permissible
strategy at the mildest end of a spectrum of denormalizing approaches-milder than
the reintegrative shaming described in the criminal justice literature, and
diametrically opposed to outright stigmatization, which is generally considered
ethically impermissible. Given the severe stigma of mental illness in East Asia,
adopting the dominant Western view of suicide as solely a psychiatric concern
would not be justified. Weak denormalization strategies in East Asia should be
culturally tailored and rigorously tested on a small scale. They should include
social supports, praise for the bravery of those of who seek help, and strategies
to reduce shame regarding perceived social failure.
PMID- 28696952
TI - Total Elbow Arthroplasty: A Systematic Review.
AB - BACKGROUND: Most total elbow arthroplasty (TEA) designs aim to replicate anatomy
and provide stability in the treatment of the degenerative elbow joint. Given the
promising results that have been reported following the use of TEA for the
treatment of complex fractures, the indications for this procedure are growing.
The objective of the present study was to review the most recent literature on
the results of the most commonly performed TEAs. METHODS: A comprehensive
literature search was conducted. All relevant studies were reviewed according to
a set of predefined inclusion and exclusion criteria. After the initial
assessment, 2 authors extracted data from the included articles. Groups were
created on the basis of the design of TEA implant, the type of implant (linked or
unlinked), and the indication for treatment. Outcome parameters were survival
rate, pain, range of motion, complications, and specific elbow outcome scores.
RESULTS: Seventy-three articles involving a total of 9,379 TEAs were included.
The level of evidence was primarily Level IV. Nineteen specific designs of TEA
implants were described, including the Souter-Strathclyde (n = 2,387), Coonrad
Morrey (n = 1,586), Kudo (n = 560), and GSB III (n = 498). The most common
indication for TEA was rheumatoid arthritis (70%). The weighted mean survival
rate for the linked and unlinked prostheses was 85.5% at 7.8 years and 74% at
12.3 years, respectively. For the Coonrad-Morrey, Souter-Strathclyde, and GSB
III, the weighted mean survival rate was 87.2% at 7.2 years, 70.6% at 14.2 years,
and 81.7% at 9.5 years, respectively. The range of motion after TEA was good
overall, with a mean flexion angle of 129 degrees and a mean extension lag angle
of 30 degrees . The complication rates ranged from 11% to 38%, with clinical
loosening being the most frequently reported complication (7%). CONCLUSIONS: The
results of TEA are respectable overall. It appears that there are small
differences between designs. However, despite the fairly good functional results
and elbow scores, the survival and complication rates are still not as favorable
as those following arthroplasties in other joints. LEVEL OF EVIDENCE: Therapeutic
Level IV. See Instructions for Authors for a complete description of levels of
evidence.
PMID- 28696955
TI - Pediatric blepharokeratoconjunctivitis: is there a 'right' treatment?
AB - PURPOSE OF REVIEW: This article highlights the importance of recognizing
blepharokeratoconjunctivitis (BKC) in children and reviews the clinical
characteristics and current therapeutic modalities. RECENT FINDINGS: The mainstay
of BKC treatment remains controlling the meibomian gland inflammation and
treating cobormid conditions. BKC can occur in the setting of ocular rosacea and
Demodex infestation. Small studies have shown treatment benefits of topical
cyclosporine A as well as oral azithromycin in pediatric BKC. SUMMARY: BKC is a
cause for visual loss in children, and therefore pediatric ophthalmologists
should be more vigilant about early diagnosis and long-term treatment. There is a
lack of randomized controlled trials on this topic and no standardized outcome
measures. Better ways to measure the clinical outcome of various treatment
modalities need to be developed.
PMID- 28696956
TI - Long-term Outcomes with Anti-TNF Therapy and Accelerated Step-up in the
Prospective Pediatric Belgian Crohn's Disease Registry (BELCRO).
AB - BACKGROUND: Accelerated step-up or anti-tumor necrosis factor (TNF) before first
remission is currently not recommended in pediatric Crohn's disease. METHODS:
Five-year follow-up data from a prospective observational cohort of children
diagnosed with Crohn's disease in Belgium were analyzed. Disease severity was
scored as inactive, mild, or moderate to severe. Remission or inactive disease
was defined as sustained if lasting >=2 years. Univariate analyses were performed
between anti-TNF-exposed versus naive patients and anti-TNF before versus after
first remission and correlations assessed with primary outcomes average disease
severity and sustained remission. RESULTS: A total of 91 patients (median [IQR]
age 12.7 [10.9-14.8] yrs, 53% male) were included. Disease location was 12% L1,
23% L2, and 64% L3 with 76% upper gastrointestinal and 30% perianal involvement.
Disease severity was 25% mild and 75% moderate to severe. Of 66 (73%) anti-TNF
exposed patients, 34 (52%) had accelerated step-up. Anti-TNF use was associated
with age (13.1 [11.5-15.2] versus 11.8 [8.7-13.8] yrs; P < 0.05), L2 (29% versus
8%; P = 0.04), and average disease severity (1.7 [1.4-1.9] versus 1.4 [1.3-1.6];
P < 0.001). Duration of anti-TNF correlated with average disease severity (r =
0.32, P = 0.002). Accelerated step-up was also associated with age (13.3 [12.1
15.9] versus 12.5 [10.2-14.1]; P = 0.02) and average disease severity (1.8 [1.6
1.9] versus 1.6 [1.3-1.8]; P = 0.002). Duration of sustained remission was
similar in all patients, and no serious infections, cancer, or deaths were
reported. CONCLUSIONS: Anti-TNF therapy and accelerated step-up in older patients
with more severe disease leads to beneficial long-term outcomes.
PMID- 28696957
TI - Association of Inflammatory Bowel Disease and Urolithiasis in Hospitalized
Pediatric Patients.
AB - BACKGROUND: Urolithiasis is rare in pediatric patients. All patients with
inflammatory bowel disease (IBD) have an increased risk of urolithiasis, but this
risk is poorly quantified in children. The objective of this study is to evaluate
the association of IBD with urolithiasis, assess surgical outcomes, and analyze
the financial burden for children hospitalized with urolithiasis and comorbid
IBD. METHODS: The triennial Healthcare Cost and Utilization Project Kids'
Inpatient Database for years 1997 to 2012 was used to evaluate the association
between urolithiasis and IBD in hospitalized, nonpregnant children ages 5 to 20
years old. Billing codes were used to define conditions. Logistic regression
analysis quantified the association between IBD types and urolithiasis. Length of
hospital stay, costs, procedures, and complications were compared between
urolithiasis patients with and without IBD. RESULTS: Among 8,828,522 hospital
admissions, we identified 36,771 admissions with a primary diagnosis of
urolithiasis. Of these cases, 230 were associated with Crohn's disease (odds
ratios, 1.99; 95% confidence interval, 1.74-2.27) and 102 with ulcerative colitis
(odds ratio, 1.63; 95% confidence interval, 1.34-1.99). Urolithiasis patients
with ulcerative colitis, but not Crohn's disease, had significantly increased
length of stay and costs. Patients with either IBD had a decreased number of
urologic procedures. CONCLUSIONS: The diagnosis of urolithiasis in pediatric
patients is associated with IBD, and those with ulcerative colitis have longer
hospital stays and greater costs. Patients with IBD have fewer urologic
procedures associated with their urolithiasis diagnosis.
PMID- 28696958
TI - Rock Climbing-Related Bone Marrow Edema of the Hand: A Follow-up Study.
AB - OBJECTIVE: Sport climbers strain passive and active anatomical structures of
their hands and fingers to the maximum during training or competition. This study
was designed to investigate bone marrow edema (BME) in rock climbing athletes.
DESIGN: Systematic detection, treatment, and follow-up investigation of rock
climbing athletes with BME of the hand. SETTING: Primary-level orthopedic surgery
and sports medicine division of a large academic medical center. PATIENTS: Thirty
one high-level climbers with diffuse pain in the hand and wrist joint caused by
rock climbing were included in this study. INTERVENTIONS: The therapy consisted
of consequent stress reduction and a break from sports. MAIN OUTCOME MEASURES:
Reduction of BME shown through magnetic resonance imaging (MRI) and regaining of
preinjury climbing levels (Union Internationale des Associations d' Alpinisme
metric scale). RESULTS: In 28 patients, MRI revealed osseous edema because of
overload at the respective area of interest, mainly in the distal radius, the
distal ulna, or the carpal bones, which could not be otherwise diagnosed as
inflammations, tumors, or injuries. We classified these edemas and fractures of
the hamate because of overload. The edema was a stress reaction to highly
intensive training and climbing with presumably high traction to the wrist area.
The control MRIs demonstrated that even with a consequent stress reduction, the
edemas required 3 to 4 months to disappear completely. CONCLUSIONS: Climbers with
nonspecific, diffuse pain in the wrist and/or the fingers should be examined with
MRI to detect or exclude the diagnosis of a BME.
PMID- 28696959
TI - National Partnership for Maternal Safety: Consensus Bundle on Severe Hypertension
During Pregnancy and the Postpartum Period.
AB - Complications arising from hypertensive disorders of pregnancy are among the
leading causes of preventable severe maternal morbidity and mortality. Timely and
appropriate treatment has the potential to significantly reduce hypertension
related complications. To assist health care providers in achieving this goal,
this patient safety bundle provides guidance to coordinate and standardize the
care provided to women with severe hypertension during pregnancy and the
postpartum period. This is one of several patient safety bundles developed by
multidisciplinary work groups of the National Partnership for Maternal Safety
under the guidance of the Council on Patient Safety in Women's Health Care. These
safety bundles outline critical clinical practices that should be implemented in
every maternity care setting. Similar to other bundles that have been developed
and promoted by the Partnership, the hypertension safety bundle is organized into
four domains: Readiness, Recognition and Prevention, Response, and Reporting and
Systems Learning. Although the bundle components may be adapted to meet the
resources available in individual facilities, standardization within an
institution is strongly encouraged. This commentary provides information to
assist with bundle implementation.
PMID- 28696960
TI - Sinus Floor Augmentation With Ambient Blood and an Absorbable Collagen Sponge: A
Prospective Pilot Clinical Study.
AB - PURPOSE: The aim of this study was to clinically, radiologically, and
histologically evaluate a sinus augmentation technique using a resorbable
collagen sponge to maintain space between the Schneiderian membrane and the
residual crestal bone. MATERIALS AND METHODS: Patients with partially edentulous
maxillae were clinically and radiographically evaluated for implant placement. A
total of 10 consecutive patients with the bone height for implant placement (<4.0
mm) were enrolled in the study. The lateral maxillary wall was surgically exposed
and the Schneiderian membrane was carefully elevated. A collagen wound dressing
was placed in the antral area between the sinus floor and the raised membrane.
The vertical sinus floor height was calculated using cone-beam computed
tomography before the surgical procedure (baseline) and at 6 months
postoperative. Immediately after the second scan, a core biopsy was removed for
histological evaluation. The biopsy site was then further prepared for implant
placement in the same location. RESULTS: Biopsies showed mature cancellous bone
with a predominantly lamellar structure. Well-vascularized intertrabecular spaces
were filled with connective tissue and bone marrow. Analysis of bone height
changes showed significant mean (SD) differences before and after procedures in
anterior (2.67 +/- 0.62 mm and 11.15 +/- 1.1 mm), medial (2.98 +/- 0.55 mm and
10.96 +/- 0.77 mm), and posterior (3.17 +/- 0.91 mm and 10.63 +/- 0.51 mm)
maxillary jaw locations (P = 0.005). CONCLUSION: The collagen sponge provided an
effective substrate for osseous regeneration of the sinus floor.
PMID- 28696961
TI - Current body composition measurement techniques.
AB - PURPOSE OF REVIEW: The current article reviews the most innovative and precise,
available methods for quantification of in-vivo human body composition. RECENT
FINDINGS: Body composition measurement methods are continuously being perfected.
Ongoing efforts involve multisegmental and multifrequency bioelectrical impedance
analysis, quantitative magnetic resonance for total body water, fat, and lean
tissue measurements, imaging to further define ectopic fat depots. Available
techniques allow for the measurement of fat, fat-free mass, bone mineral content,
total body water, extracellular water, total adipose tissue and its subdepots
(visceral, subcutaneous, and intermuscular), skeletal muscle, select organs, and
ectopic fat depots. SUMMARY: There is an ongoing need for methods that yield
information on metabolic and biological functions. Based on the wide range of
measurable properties, analytical methods and known body composition models,
clinicians, and scientists can quantify a number of body components and with
longitudinal assessment, can track changes in health and disease with
implications for understanding efficacy of nutritional and clinical
interventions, diagnosis, prevention, and treatment in clinical settings. With
the greater need to understand precursors of health risk beginning prior to
conception, a gap exists in appropriate in-vivo measurement methods with
application beginning during gestation, that is, fetal development.
PMID- 28696963
TI - Superspecialization and Health Care Cost.
PMID- 28696962
TI - The Use of Endobronchial Ultrasound-guided Transbronchial Needle Aspiration
Cytology Specimens for Programmed Death Ligand 1 Immunohistochemistry Testing in
Non-Small Cell Lung Cancer.
PMID- 28696964
TI - Impact of EBUS-TBNA on PET-CT Imaging of Mediastinal Nodes.
AB - BACKGROUND: Positron emission tomography-computed tomography (PET-CT) with
fluorine-18-fluorodeoxyglucose has a high sensitivity in detecting malignancy in
patients suspected of lung cancer but a low specificity as inflammatory reactions
can also result in metabolic activity. Furthermore, it is assumed that invasive
pulmonary procedures with biopsies from benign lesions can induce metabolic
activity resulting in false-positive results. However, this hypothesis lacks
solid evidence. We aimed to evaluate how often endobronchial ultrasound (EBUS)
with biopsies from benign lesions are followed by false-positive results.
METHODS: Patients with suspected or proven lung cancer admitted for invasive
pulmonary procedures in a 6-year period were retrospectively reviewed. Patients
who had at least 1 nonmalignant mediastinal lymph node (MLN) biopsied 1 to 13
days before PET-CT were included. The number of false-positive and true-negative
results shortly after EBUS biopsy of nonmalignant MLN was reviewed. RESULTS: Of
1025 patients, 216 patients were referred for PET-CT 1 to 13 days after biopsy.
Of these, 107 patients had at least 1 MLN biopsied. From a total of 198 biopsied
MLNs, we found 62% without metabolic activity (benign) and 38% with metabolic
activity. In 5% the metabolic activity could be explained by an infection or
inflammatory disorder, in 15% no cytologic follow-up was available, in 1%
malignancy was confirmed at follow-up, and in 3% the patients were not possible
to follow-up. In the remaining 14%, no other reasonable explanation for the
metabolic activity was found other than the biopsy. CONCLUSIONS: EBUS with biopsy
do not necessarily result in PET activity. Therefore, PET-positive results should
always be taken seriously, even when PET is performed shortly after biopsies.
PMID- 28696965
TI - Influence of the Learning Effect on the Diagnostic Yield of Endobronchial
Ultrasound-guided Transbronchial Needle Aspiration of Mediastinal and Hilar Lymph
Nodes.
AB - BACKGROUND: The diagnostic yield of conventional transbronchial needle aspiration
(TBNA) is characterized by a learning effect. The aim of this retrospective study
was to verify whether a learning curve similarly affected the yield of
endobronchial ultrasound-guided (EBUS)-TBNA. To this end, we evaluated the
sensitivity and diagnostic accuracy of EBUS-TBNA during the first 3 years of
activity. METHODS: EBUS-TBNA was performed by 2 operators with no previous
experience in this technique. Cytologic samples were obtained from mediastinal
and hilar lymph nodes enlarged at a chest computed tomography scan and/or with
increased fluorodeoxyglucose uptake at computed tomography/positron emission
tomography scan in patients with suspected lung cancer. The cytologic diagnosis
of EBUS-TBNA samples has been compared with the final diagnosis obtained from
further diagnostic procedures, surgery, or clinical-radiologic follow-up.
RESULTS: From October 2012 to October 2015, we collected 408 EBUS-TBNA cytologic
samples from 313 patients: 223 samples were positive for metastatic involvement
and 185 were nonmetastatic. The latter included 137 true-negative and 48 false
negative results. The final diagnosis comprised 271 metastatic and 137
nonmetastatic lymph nodes. The overall sensitivity for cancer was 82% and
diagnostic accuracy was 88%. Sensitivity and accuracy per year were as follows:
first year, 78% and 82% in 90 nodal samples; second year, 83% and 89% in 144
nodal samples; third year, 85% and 91% in 174 nodal samples. CONCLUSIONS: EBUS
TBNA can be considered as a reliable tool even if performed by operators without
previous experience in this procedure, and the diagnostic yield continues to
increase progressively over a long time.
PMID- 28696966
TI - Defining a Ventilation Strategy for Flexible Bronchoscopy on Mechanically
Ventilated Patients in the Medical Intensive Care Unit.
AB - BACKGROUND: Flexible bronchoscopy (FB) in intubated patients on mechanical
ventilation increases airway resistance. During FB, two ventilatory strategies
are possible: maintaining tidal volume (VT) while maintaining baseline CO2 or
allowing reduction of VT. The former strategy carries risk of hyperinflation due
to expiratory flow limitation with FB. The aim of the authors was too study end
expiratory lung volume (EELV) during FB of intubated subjects while limiting VT.
METHODS: We studied 16 subjects who were intubated on mechanical ventilation and
required FB. Changes in EELV were measured by respiratory inductance
plethysmography. Ventilator mechanics, EELV, and arterial blood gases, were
measured. RESULTS: FB insertions decreased EELV in 64% of cases (-325+/-371 mL)
and increased it in 32% of cases (65+/-59 mL). Suctioning decreased EELV in 76%
of cases (-120+/-104 mL) and increased it in 16% of cases (29+/-33 mL).
Respiratory mechanics were unchanged. Pre-FB and post-FB, PaO2 decreased by 61+/
96 mm Hg and PaCO2 increased by 15+/-7 mm Hg. CONCLUSIONS: There was no
clinically significant increase in EELV in any subject during FB. Decreases in
EELV coincided with FB-suctioning maneuvers. Peak pressure limiting ventilation
protected the subject against hyperinflation with a consequent, well-tolerated
reduction in VT, and hypercapnea. Suctioning should be limited, especially in
patients vulnerable to derecruitment effect.
PMID- 28696967
TI - Long-term Outcome of Short Metallic Stents for Lobar Airway Stenosis.
AB - BACKGROUND: Whereas stents are considered an excellent treatment for proximal
central major airway stenosis, the value of stenting for distal lobar airway
stenosis is still controversial. Our aim was to explore the short-term and long
term outcome of metallic stents placed for benign and malignant lobar airway
stenosis. METHODS: Between July 2007 and July 2014, 14 patients underwent small
airway stent insertion. The clinical follow-up included serial semiannual
physical examinations, pulmonary function tests, imaging, and bronchoscopy.
RESULTS: The etiologies for airway stenosis were: early post-lung transplantation
bronchial stenosis (N=5), sarcoidosis (N=1), amyloidosis (N=1), anthracofibrosis
(N=1), right middle lobe syndrome due to external lymph node compression (N=1),
lung cancer (N=4), and stenosis of the left upper lobe of unknown etiology (N=1).
Stents were placed in the right upper lobe bronchus (N=2), right middle lobe
bronchus (N=6), left upper lobe bronchus (N=4), linguar bronchus (N=1), and left
lower lobe bronchus (N=1). The median follow-up period ranged from 2 to 72 months
(median 18 mo). Immediate relief of symptoms was achieved in the vast majority of
patients (13/14, 92%). Out of 10 patients with benign etiology for stenosis, 9
(90%) experienced sustained and progressive improvement in pulmonary function
tests and clinical condition. CONCLUSIONS: We describe our positive experience
with small stents for lobar airway stenosis; further prospective trials are
required to evaluate the value of this novel modality of treatment.
PMID- 28696968
TI - Bronchogenic Cyst Abscess.
PMID- 28696969
TI - Endobronchial Protrusion of an Amplatzer Plug After Embolization of the Pulmonary
Artery.
PMID- 28696970
TI - Image Characteristics of Lung Abscess by Convex-Probe Endobronchial Ultrasound.
PMID- 28696971
TI - Where do Sutures Go? They Migrate and Erode!
PMID- 28696972
TI - How Does the Doctor Feel?
PMID- 28696973
TI - Mediastinal Hematoma Following Endobronchial Ultrasound-guided Transbronchial
Needle Aspiration.
PMID- 28696974
TI - Complete Heart Block Following Cold Saline Lavage During Bronchoscopy.
PMID- 28696975
TI - Pulmonary Hemorrhage Treated With Oxidized Regenerated Cellulose.
PMID- 28696976
TI - Bilateral Patellar Tendon Tears After a Fall From Standing Position: Do You Mind
Systemic Diseases and Medications?
PMID- 28696977
TI - ACSM Clinician Profile.
PMID- 28696978
TI - On Spleens and Genes.
PMID- 28696980
TI - Dermatology Issues in Sports.
PMID- 28696981
TI - Cuboid Syndrome: Whip It Good!
PMID- 28696982
TI - A Holistic Antidoping Approach for a Fairer Future for Sport.
PMID- 28696983
TI - Exercise in the Treatment of Chronic Disease: An Underfilled Prescription.
PMID- 28696984
TI - The Youth Sports Machine: Destructive Juggernaut or Vehicle for Success?
PMID- 28696985
TI - Tart Cherry Juice in Athletes: A Literature Review and Commentary.
AB - Tart cherry (TC) juice has many antioxidant and anti-inflammatory polyphenol
compounds. TC lessens pain and accelerates strength recovery after exercise and
decreases blood markers of inflammation/oxidative stress. These improvements
occur in both strength and endurance exercise. TC supplementation may not be
optimal during the adaptation/build stage of training. However, excessive
inflammatory/oxidative stress during single-day intense training/competition or
multiday tournaments may delay return to peak form. In this stage, where recovery
(not adaptation) is the priority, TC may be beneficial. Timing and dosage vary
widely, but most studies use 8 to 12 oz (1 oz if concentrate form) twice a day, 4
to 5-d loading phase before the event, and 2 to 3 d after to promote recovery.
Therefore, for an athlete who has already peaked in training and looking to
improve recovery and faster return to competition, TC may be beneficial.
PMID- 28696986
TI - Fueling the Triathlete: Evidence-Based Practical Advice for Athletes of All
Levels.
AB - Triathletes need to effectively fuel during training and racing to maximize their
potential for success. While most research on fueling has focused on elite male
triathletes, triathlon participation encompasses a broader demographic of racers
ranging from those with aspirations of winning to those whose goals are
completion. Carbohydrate is the primary macronutrient for fueling endurance
activities. Athletes can usually tolerate 60 to 90 mg.h in the form of multiple
different carbohydrate sources. Athletes should drink as thirst dictates and
consider sodium replacement of sweat loss especially in individuals with a
history of exercise-associated muscle cramps. Caffeine is a known ergogenic aid
that could be dosed at 3 mg.kg to maximize benefits of mental alertness while
limiting potential side effects. Athletes need to balance fueling with
development of exercise-induced gastrointestinal syndrome. As demographics of
race participants change, understanding the special fueling needs of obese
triathletes can encourage participation while minimizing bad outcomes.
PMID- 28696987
TI - Nutritional Supplements for the Treatment and Prevention of Sports-Related
Concussion-Evidence Still Lacking.
AB - Concussions are common neurologic events that affect many athletes. Very little
has been studied on the treatment of concussions with supplements and
medications. The U.S. Food and Drug Administration (FDA) reminds us that no
supplement has been proven to treat concussions. Many animal studies show that
supplements have potential for improving the effects of a brain injury but none
have been shown to be of consistent benefit in human studies. Animal studies on
severe traumatic brain injury (TBI) may not therefore be applicable transfer to
sports-related concussions (SRC).Of the many supplements reviewed in this
article, omega-3 fatty acids (Omega-3 FA) have potential for SRC treatment but in
the one human trial those taking higher dosages preinjury had more concussions.
In animal studies, postinjury administration was as effective as pretreatment. N
acetyl-cysteine has demonstrated a positive short-term effect on blast injuries
in soldiers if administered within 24 h, but there are no studies in SRC.
Caffeine, conversely, may be detrimental if taken after SRC. Lower serum levels
of vitamins D, C, or E preinjury have worse outcomes in animal studies. Preinjury
correction of deficiencies may be of benefit. Current human trials for
nicotinamide ribose, melatonin, and branched chain amino acids (BCAA) may soon
provide more evidence for the use of these supplements to reduce the impact of
SRC in athletes.
PMID- 28696988
TI - Body Mass Index as a Predictor of Injuries in Athletics.
AB - The quest to identify injury risk factors in sports has been an ongoing and well
researched field in the world of sports medicine. Knowing some of these factors
helps keep sports participation safe. Both intrinsic and extrinsic factors have
been studied. Body mass index (BMI) is widely known to contribute to several
medical conditions. Its association with some sports injuries has been
established but the information is vast, with few studies that are randomized
controlled trials. It is important to analyze these studies and confirm whether
BMI is a predictor of lower-extremity injuries. Such knowledge allows for better
effective treatment and prevention strategies. This article will summarize
current evidence of association between BMI and lower-extremity injuries in
athletes and whether BMI is a predictor of lower-extremity injuries.
PMID- 28696989
TI - Exercise in the Prevention and Treatment of Breast Cancer: What Clinicians Need
to Tell Their Patients.
AB - In 2016, nearly a quarter-million women were diagnosed with invasive breast
cancer, the second deadliest cancer type. Lifestyle behaviors are well
established risk factors for both the development of, and negative outcomes from,
breast cancer. New findings demonstrate that engaging in even minimal amounts of
exercise is protective against breast cancer. Further, numerous studies have
identified the role of exercise in the treatment of breast cancer and improvement
in treatment side effects, quality of life, and overall survival. Unfortunately,
few patients are physically active due to multiple barriers. Physicians may be
helpful in engaging patients in being more active. Further research is necessary
to identify programs and approaches to help patients both with, and at-risk for,
breast cancer to engage in exercise.
PMID- 28696990
TI - Prescribing Exercise to Individuals with Disabilities: What Are the Concerns?
AB - It is well known that individuals with disabilities, constituting 15% to 20% of
the adult population, experience a disproportionate risk of cardiometabolic
disease and are more likely to live sedentary lifestyles when compared with their
able-bodied peers. Although many complex factors likely lead to these
disparities, targeted exercise programs can be influential in improving the
health outcomes of this population. Additionally, it is important to keep several
factors in mind when tailoring the exercise prescription for individuals with
varied types of disability, given unique factors related to medical history,
mobility, and community barriers. By safely engaging individuals with
disabilities in exercise programs, clinicians can promote inclusion while making
a significant contribution to health outcomes, ensuring that the principles of
"Exercise is Medicine" are accessible to individuals of all abilities.
PMID- 28696991
TI - The Practice of Sport in Multiple Sclerosis: Update.
AB - The practice of sport by multiple sclerosis patients has long been controversial.
Recent studies, however, show that both sport and physical activity are essential
for these patients. Indeed, they help to cope with the effects of multiple
sclerosis, such as fatigue, reduced endurance, loss of muscle mass, and reduction
of muscle strength. The beneficial effects of physical activity on these patients
have been underlined in several studies, whereas those of practicing sport have
been the subject of fewer evaluations and assessments. The aim of this update is
to report on the effects of sport on multiple sclerosis patients. The benefits of
sport have been demonstrated in several studies. It helps multiple sclerosis
patients to increase their balance, resistance to fatigue, mobility and quality
of life. Several biases in these studies do not enable us to recommend the
practice of some of these sports on a routine basis.
PMID- 28696992
TI - Triathlon Medical Coverage: A Guide for Medical Directors.
AB - Interest and participation in triathlon has grown rapidly over the past 20 yr and
with this growth, there has been an increase in the number of new events. To
maximize the safety of participation, triathlons require medical directors to
plan and oversee medical care associated with event participation. Provision of
proper medical care requires knowledge of staffing requirements, common triathlon
medical conditions, impact of course design, communication skill, and a
familiarity of administrative requirements. These guidelines serve as a tool for
triathlon medical and race directors to improve race safety for athletes.
PMID- 28696993
TI - Special Communication of a Case of Hypovolemic-Associated EAH: Lessons Learned
During Recovery.
AB - Severe exercise-associated hyponatremia (EAH) is largely dilutional, whereas
contributions of sodium loss remain equivocal. We present a case of EAH with
encephalopathy involving an experienced male cyclist with no recollection of the
event. We thereby conducted a retrospective analysis of biochemical trajectories
during hospital recovery. The normalization of serum [Na], in context with
changes in other variables, offered a 'reverse' perspective of the underlying
pathophysiology. The following biochemical changes were temporally observed, with
the return of normonatremia: 1) a decrease in serum potassium and calcium
concentrations (absence of extracellular fluid dilution); 2) a decrease in total
protein, blood urea nitrogen, hematocrit and hemoglobin (plasma volume
expansion); and 3) an increase in mean platelet and red cell corpuscular volumes
(cellular expansion after total body water and sodium deficits). Collectively,
these temporal changes provide biochemical evidence suggesting that this
patient's severe symptomatic EAH was associated with volume depletion from
underreplaced sodium losses.
PMID- 28696994
TI - Zika Virus: The Topic That Should Not Be Forgotten in Sport Medicine.
PMID- 28696995
TI - Response to the Letter to the Editor.
PMID- 28696996
TI - Tranexamic Acid: What Is Known and Unknown, and Where Do We Go From Here?
PMID- 28696997
TI - Number of Offspring and Cardiovascular Disease Risk in Men and Women: The Role of
Shared Lifestyle Characteristics.
AB - BACKGROUND: Previous studies of the number of offspring and cardiovascular
disease (CVD) report conflicting findings. We re-examined this association in
both sexes to clarify the role of the cardiometabolic changes that women
experience during pregnancy versus shared lifestyle characteristics. METHODS: We
studied 180,626 women and 133,259 men participating in the UK Biobank cohort who
were free of CVD at baseline. CVD events were obtained from hospital and death
registers. Analyses were conducted using Cox proportional hazards regression.
RESULTS: The incidence rates of overall CVD were six per 1000 person-years for
women and nine per 1000 person-years for men. Number of children showed an
association with risk of CVD among women; the adjusted HR (95% CI) was 1.2 (1.1,
1.3) for one, 1.1 (1.0, 1.2) for two, 1.2 (1.1, 1.3) for three, and 1.2 (1.1,
1.4) for four or more as compared to none. Number of children was also associated
with CVD among men; the adjusted HR (95% CI) was 1.1 (1.0, 1.2) for one, 1.0
(0.96, 1.1) for two, 1.1 (1.0, 1.2) for three, and 1.1 (1.0, 1.3) for four or
more as compared to none. There was no evidence of heterogeneity in the
associations between sexes (Pinteraction = 0.80). Number of offspring also showed
similar associations with ischemic heart disease and hypertensive disorders in
both sexes. CONCLUSIONS: We observed similar associations between number of
offspring and CVD in both sexes. The association among women might therefore be
largely explained by unobserved behavioral and lifestyle characteristics.
PMID- 28696998
TI - Evaluation and management of vaginoplasty complications.
AB - PURPOSE OF REVIEW: Indications for vaginoplasty include congenital conditions
such as adrenal hyperplasia, cloacal malformations, and Mullerian agenesis,
acquired conditions including stenosis from radiation or surgical resection for
malignancy, and gender affirmation. All vaginoplasty techniques carry significant
risk of both immediate and long-term complications. RECENT FINDINGS: The purpose
of this study is to provide a review of the evaluation and management of the
neovagina, addressing management of human papilloma virus infections and
complications including stenosis, fistula, prolapse, and neovaginal colitis.
SUMMARY: Gynecologists who care for patients who have had a vaginoplasty need to
understand the importance of long-term follow up and care, including evaluation
and management of complications.
PMID- 28696999
TI - The expanding role of scapular free-flaps.
AB - PURPOSE OF REVIEW: The review evaluates the expanding role of scapular free flaps
and its application in various complex head and neck defects. RECENT FINDINGS:
The recent literature published focuses on the use of three-dimensional modeling
for maxillectomy defects, expanded uses in both the megaflap, the various
application of the scapular tip flap, and the feasibility of osseointegrated
implants. SUMMARY: The subscapular system of flaps remains a versatile option in
head and neck reconstruction. It continues to be one of the best options for
large defects requiring generous soft tissue, muscle, and bone. Three-dimensional
modeling is currently being applied to complex maxillary defects resulting in
increased accuracy and efficiency of reconstruction. Expanded uses have also
adopted the latissimus dorsi muscle in conjunction with the scapular bony flap to
be used in large defects with resulting decreased fistula rates. Finally, there
is sufficient evidence that supports the use of dental implantation into the
scapula bone with successful retention rates.
PMID- 28697000
TI - Evaluation and management of syndromic congenital hearing loss.
AB - PURPOSE OF REVIEW: The purpose of this review is to review the evaluation and
management of children with syndromic hearing loss. Specific syndromes and the
impact of those syndromes on managing hearing loss will be discussed. RECENT
FINDINGS: Improved molecular testing has increased the ability to identify
syndromes-associated hearing loss. Accurate diagnosis of syndromic hearing loss
can guide discussions regarding prognosis and appropriate management options for
the hearing impairment. SUMMARY: A significant portion of childhood hearing loss
is associated with a syndrome. Depending on the syndrome, surgical intervention
including a bone-anchored hearing aid or cochlear implant may be helpful. In the
future, targeted gene therapies may become a viable option for treating syndromic
hearing loss.
PMID- 28697001
TI - The genetics of Hodgkin lymphoma: an overview and clinical implications.
AB - PURPOSE OF REVIEW: The goal of this review is to give an overview of the genetics
of classical Hodgkin lymphoma. Copy number changes, somatic mutations, genome
wide association studies, changes in gene expression, familial classical Hodgkin
lymphoma and epigenetic changes will be reviewed. In doing so, special focus is
placed on the way recent discoveries have influenced clinical research,
diagnostics, treatment and remission monitoring. Furthermore, emphasis is put on
how these advances can help to advance the treatment of elderly patients who have
a markedly worse prognosis than younger patients. RECENT FINDINGS: Frequent
amplifications of the 9p24.1 locus in classical Hodgkin lymphoma could be the
basis for the success of immune checkpoint inhibitors targeting PD-1 or PD-L1 in
this disease. The same amplification also affects the JAK/STAT pathway, which has
also been targeted in recent clinical trials. Hodgkin lymphoma-specific copy
number alterations and mutations have recently been found to be detectable in
cell-free DNA. This could provide the basis for advances in the detection of
residual disease during treatment and while monitoring patients in remission.
SUMMARY: The advent of new technologies such as massive parallel sequencing has
improved our understanding of the genetics of classical Hodgkin lymphoma. Some of
these discoveries are now being translated into clinical research in the form of
new diagnostics and treatments.
PMID- 28697002
TI - Re-irradiation of cervical and endometrial cancer.
AB - PURPOSE OF REVIEW: Re-irradiation historically has been associated with
unacceptable toxicity and limited benefit. Recent advances in radiotherapy can
change the treatment paradigm to provide new salvage treatments for recurrences
of cervical and endometrial cancer. RECENT FINDINGS: Image-guided brachytherapy
is an effective method for salvaging central pelvic recurrence, although it has
resulted in 20-25% severe late toxicity. Pelvic sidewall disease is not
accessible to brachytherapy, so a combined modality approach with radical surgery
and intraoperative radiotherapy is an alternative approach. Stereotactic body
radiotherapy (SBRT) now provides the option of radical re-irradiation with local
control rates of 50-80% and a low incidence of severe late complications.
SUMMARY: Initial outcomes using SBRT and image-guided brachytherapy for re
irradiation of gynaecological cancer are encouraging. There has been good local
control and acceptable toxicity. Further, large-scale studies are required to
define optimal target doses and OAR limits.
PMID- 28697003
TI - The 'respect rather than resect' principle in mitral valve repair: the lateral
dislocation of the P2 technique.
AB - BACKGROUND: Leaflet resection represents the reference standard for surgical
treatment of mitral valve (MV) regurgitation. New approaches recently proposed
place emphasis on respecting, rather than resecting, the leaflet tissue to avoid
the drawbacks of the 'resection' approach. OBJECTIVES: The lateral dislocation of
mid portion of mitral posterior leaflet (P2) technique for MV repair is a
nonresectional technique in which the prolapsed P2 segment is sutured to normal
P1 segment. Our study evaluates the effectiveness of this technique. PATIENTS AND
METHODS: We performed the procedure on seven patients. Once ring annular sutures
were placed, the prolapsed P2 segment was dislocated toward the normal P1 segment
with a rotation of 90 degrees and without any resection. If present, residual
clefts between P2 and P3 segments were closed. Once the absence of residual
mitral regurgitation is confirmed by saline pressure test, ring annuloplasty was
completed. The valve was evaluated using transesophageal echocardiography in the
operating room and by transthoracic echocardiography before discharge. RESULTS:
At the last follow-up visit, transthoracic echocardiography revealed no mitral
regurgitation and normal TRANSVALVULAR gradients. CONCLUSION: The lateral
dislocation of P2 is an easily fine-tuned technique for isolated P2 prolapse,
with the advantage of short aortic cross-clamp and cardiopulmonary bypass times.
We think it might be very favorable in older and frail patients. Long-term follow
up is necessary to assess the durability of this technique.
PMID- 28697004
TI - Experimental Models of Endotheliopathy: Impact of Shock Severity.
AB - BACKGROUND: Hemorrhagic shock (HS) followed by resuscitation is often associated
with sympathoadrenal activation (SAA) and endothelial damage (ED). OBJECTIVE: We
aimed to evaluate the impact of HS alone on the magnitude of SAA and consecutive
ED, and to characterize potential targets for a standardized and reproducible
model of HS-induced endotheliopathy in rats. METHODS: Rats were subjected either
to a volume-controlled HS (40% of total blood volume: v-HS group) or to a
laboratory-guided HS (l-HS) targeting base deficit (BD) more than 5.5 mmol/L
and/or lactate more than 2.2 mmol/L using a pressure-controlled volume loss.
RESULTS: At the end of shock, mean arterial pressure was significantly higher in
the v-HS than the l-HS group (36 +/- 5.6 vs. 30 +/- 3.0 mmHg; P < 0.01). Base
deficit and lactate were higher in l-HS than the v-HS group (BD: 9.5 +/- 2.5 vs.
3.0 +/- 1.0 mmol/L; P < 0.001; lactate: 4.1 +/- 1.3 vs. 1.6 +/- 0.6 mmol/L; P <
0.001). sVEGFR-1 and syndecan-1 were approximately 50% higher in the l-HS than
the v-HS group (% changes vs. baseline: 160 +/- 10 vs. 116 +/- 36; P < 0.01; 170
+/- 37 vs. 113 +/- 27; P < 0.001). Adrenaline was 2-fold higher in l-HS than the
v-HS group (1964 +/- 961% vs. 855 +/- 451%; P < 0.02, respectively). Moreover,
linear regression analysis revealed an independent association of shock severity
BD with syndecan-1 (rho = 0.55, P = 0.0005), sVEGFR1 (rho = 0.25, P < 0.05), and
adrenaline (rho = 0.31, P = 0.021). CONCLUSIONS: Our findings indicate that ED
has already occurred during HS without reperfusion; intensity is strongly related
to the severity of HS and consecutive SAA; and severity may appropriately be
targeted and standardized in a HS model controlled by biological endpoints such
as BD and/or lactate.
PMID- 28697005
TI - Essay.
PMID- 28697007
TI - Management of Gynecomastia in Patients With Different Body Types: Considerations
on 312 Consecutive Treated Cases.
PMID- 28697008
TI - Reply to the Comment on: Management of Gynecomastia in Patients With Different
Body Types: Considerations on 312 Consecutive Treated Cases.
PMID- 28697009
TI - Home blood pressure predicts stroke incidence among older adults with impaired
physical function: the Ohasama study.
AB - OBJECTIVE: Several observational studies have found modifying effects of
functional status on the association between conventional office blood pressure
(BP) and adverse outcomes. We aimed to examine whether the association between
higher BP and stroke was attenuated or inverted among older adults with impaired
function using self-measured home BP measurements. METHODS: We followed 501
Japanese community-dwelling adults aged at least 60 years (mean age, 68.6 years)
with no history of stroke. Multivariate-adjusted hazard ratios for 1-SD increase
in home BP and office BP measurements were calculated by the Cox proportional
hazards model. Functional status was assessed by self-reported physical function.
RESULTS: During a median follow-up of 11.5 years, first strokes were observed in
47 participants. Higher home SBP, but not office SBP, was significantly
associated with increased risk of stroke among both 349 participants with normal
physical function and 152 participants with impaired physical function [hazard
ratio (95% confidence interval) per 14.4-mmHg increase: 1.74 (1.12-2.69) and 1.77
(1.06-2.94), respectively], with no significant interaction for physical function
(P = 0.56). Higher home DBP, but not office DBP, was also significantly
associated with increased risk of stroke (P <= 0.029) irrespective of physical
function (all P > 0.05 for interaction). Neither home BP nor office BP was
significantly associated with all-cause mortality irrespective of physical
function. CONCLUSION: Higher home BP was associated with increased risk of stroke
even among those with impaired physical function. Measurements of home BP would
be useful for stroke prevention, even after physical function decline.
PMID- 28697010
TI - Estimating population salt intake in India using spot urine samples.
AB - OBJECTIVE: To compare estimates of mean population salt intake in North and South
India derived from spot urine samples versus 24-h urine collections. METHODS: In
a cross-sectional survey, participants were sampled from slum, urban and rural
communities in North and in South India. Participants provided 24-h urine
collections, and random morning spot urine samples. Salt intake was estimated
from the spot urine samples using a series of established estimating equations.
Salt intake data from the 24-h urine collections and spot urine equations were
weighted to provide estimates of salt intake for Delhi and Haryana, and Andhra
Pradesh. RESULTS: A total of 957 individuals provided a complete 24-h urine
collection and a spot urine sample. Weighted mean salt intake based on the 24-h
urine collection, was 8.59 (95% confidence interval 7.73-9.45) and 9.46 g/day
(8.95-9.96) in Delhi and Haryana, and Andhra Pradesh, respectively. Corresponding
estimates based on the Tanaka equation [9.04 (8.63-9.45) and 9.79 g/day (9.62
9.96) for Delhi and Haryana, and Andhra Pradesh, respectively], the Mage equation
[8.80 (7.67-9.94) and 10.19 g/day (95% CI 9.59-10.79)], the INTERSALT equation
[7.99 (7.61-8.37) and 8.64 g/day (8.04-9.23)] and the INTERSALT equation with
potassium [8.13 (7.74-8.52) and 8.81 g/day (8.16-9.46)] were all within 1 g/day
of the estimate based upon 24-h collections. For the Toft equation, estimates
were 1-2 g/day higher [9.94 (9.24-10.64) and 10.69 g/day (9.44-11.93)] and for
the Kawasaki equation they were 3-4 g/day higher [12.14 (11.30-12.97) and 13.64
g/day (13.15-14.12)]. CONCLUSION: In urban and rural areas in North and South
India, most spot urine-based equations provided reasonable estimates of mean
population salt intake. Equations that did not provide good estimates may have
failed because specimen collection was not aligned with the original method.
PMID- 28697011
TI - Association between adipokines and critical illness outcomes.
AB - BACKGROUND: Adipose tissue is an endocrine organ that plays a critical role in
immunity and metabolism by virtue of a large number of hormones and cytokines,
collectively termed adipokines. Dysregulation of adipokines has been linked to
the pathogenesis of multiple diseases, but some questions have arisen concerning
the value of adipokines in critical illness setting. The objective of this review
was to evaluate the associations between blood adipokines and critical illness
outcomes. METHODS: PubMed, CINAHL, Scopus, and the Cochrane Library databases
were searched from inception through July 2016 without language restriction.
Studies reporting the associations of adipokines, leptin, adiponectin, resistin,
and/or visfatin with critical illness outcomes mortality, organ dysfunction,
and/or inflammation were included. RESULTS: A total of 38 articles were selected
according to the inclusion/exclusion criteria of the study. Significant
alterations of circulating adipokines have been reported in critically ill
patients, some of which were indicative of patient outcomes. The associations of
leptin and adiponectin with critical illness outcomes were not conclusive in that
blood levels of both adipokines did not always correlate with the illness
severity scores or risks of organ failure and mortality. By contrast, studies
consistently reported striking increase of blood resistin and visfatin,
independently of the critical illness etiology. More interestingly, increased
levels of these adipokines were systematically associated with severe
inflammation, and high incidence of organ failure and mortality. CONCLUSIONS:
There is strong evidence to indicate that increased levels of blood resistin and
visfatin are associated with poor outcomes of critically ill patients, including
higher inflammation, and greater risk of organ dysfunction and mortality. LEVEL
OF EVIDENCE: Systematic review, level III.
PMID- 28697013
TI - The clinical significance of isolated traumatic subarachnoid hemorrhage in mild
traumatic brain injury: A meta-analysis.
AB - BACKGROUND: The rates of clinical and radiographic progression and the need for
neurosurgical intervention in patients with isolated traumatic subarachnoid
hemorrhage (itSAH) after mild traumatic brain injury (Glasgow Coma Scale score,
13-15) has not been well established.The aim of this work was to review the
evidence regarding patient outcomes after mild traumatic brain injury with itSAH.
METHODS: Two authors independently extracted the data according to a predefined
protocol. The proportions of patients who had the outcomes of interest were
pooled using random-effects model. The quality of included studies was assessed
using the methodological index for nonrandomized studies scale. RESULTS: Thirteen
studies reporting on 15,327 patients met inclusion criteria, and outcomes were
pooled where available. No patient required neurosurgical intervention on
presentation to hospital, and the incidence of need for eventual neurosurgical
intervention was 0.0017% (95% confidence interval [CI], 0-0.39%). Moreover, the
pooled analyses for all patients with available data showed an incidence of 5.76%
(95% CI, 1.18-12.94%) for radiographic progression, 0.75% (95% CI, 0-2.39%) for
neurologic deterioration, and 0.60% (95% CI, 0.09-1.41%) for mortality. Only one
patient had died due to neurological injury. CONCLUSIONS: These patients
experience very low rates of radiographic progression and neurologic
deterioration and rarely require neurosurgical intervention or die due to
neurological injury. LEVEL OF EVIDENCE: Meta-analysis, level III.
PMID- 28697014
TI - Valproic acid decreases brain lesion size and improves neurologic recovery in
swine subjected to traumatic brain injury, hemorrhagic shock, and polytrauma.
AB - BACKGROUND: We have previously shown that treatment with valproic acid (VPA)
decreases brain lesion size in swine models of traumatic brain injury (TBI) and
controlled hemorrhage. To translate this treatment into clinical practice,
validation of drug efficacy and evaluation of pharmacologic properties in
clinically realistic models of injury are necessary. In this study, we evaluate
neurologic outcomes and perform pharmacokinetic analysis of a single dose of VPA
in swine subjected to TBI, hemorrhagic shock, and visceral hemorrhage. METHODS:
Yorkshire swine (n = 5/cohort) were subjected to TBI, hemorrhagic shock, and
polytrauma (liver and spleen injury, rib fracture, and rectus abdominis crush).
Animals remained in hypovolemic shock for 2 hours before resuscitation with
isotonic sodium chloride solution (ISCS; volume = 3* hemorrhage) or ISCS + VPA
(150 mg/kg). Neurologic severity scores were assessed daily for 30 days, and
brain lesion size was measured via magnetic resonance imaging on postinjury days
(PID) 3 and 10. Serum samples were collected for pharmacokinetic analysis.
RESULTS: Shock severity and response to resuscitation were similar in both
groups. Valproic acid-treated animals demonstrated significantly less neurologic
impairment between PID 1 to 5 and smaller brain lesions on PID 3 (mean lesion
size +/- SEM, mm: ISCS = 4,956 +/- 1,511 versus ISCS + VPA = 828 +/- 279; p =
0.047). No significant difference in lesion size was identified between groups at
PID 10 and all animals recovered to baseline neurologic function during the 30
day observation period. Animals treated with VPA had faster neurocognitive
recovery (days to initiation of testing, mean +/- SD: ISCS = 6.2 +/- 1.6 vs ISCS
+ VPA = 3.6 +/- 1.5; p = 0.002; days to task mastery: ISCS = 7.0 +/- 1.0 vs ISCS
+ VPA = 4.8 +/- 0.5; p = 0.03). The mean +/- SD maximum VPA concentrations, area
under the curve, and half-life were 145 +/- 38.2 mg/L, 616 +/- 150 hour.mg/L, and
1.70 +/- 0.12 hours. CONCLUSIONS: In swine subjected to TBI, hemorrhagic shock,
and polytrauma, VPA treatment is safe, decreases brain lesion size, and reduces
neurologic injury compared to resuscitation with ISCS alone. These benefits are
achieved at clinically translatable serum concentrations of VPA. LEVEL OF
EVIDENCE: Therapeutic (preclinical study).
PMID- 28697016
TI - A spontaneous pneumoperitoneum after Klebsiella-induced chronic granulomatous
cholecystitis: Is the surgery warranted?
PMID- 28697015
TI - The P50 Research Center in Perioperative Sciences: How the investment by the
National Institute of General Medical Sciences in team science has reduced
postburn mortality.
AB - Since the inception of the P50 Research Center in Injury and Peri-operative
Sciences (RCIPS) funding mechanism, the National Institute of General Medical
Sciences has supported a team approach to science. Many advances in critical
care, particularly burns, have been driven by RCIPS teams. In fact, burns that
were fatal in the early 1970s, prior to the inception of the P50 RCIPS program,
are now routinely survived as a result of the P50-funded research. The advances
in clinical care that led to the reduction in postburn death were made by
optimizing resuscitation, incorporating early excision and grafting, bolstering
acute care including support for inhalation injury, modulating the hypermetabolic
response, augmenting the immune response, incorporating aerobic exercise, and
developing antiscarring strategies. The work of the Burn RCIPS programs advanced
our understanding of the pathophysiologic response to burn injury. As a result,
the effects of a large burn on all organ systems have been studied, leading to
the discovery of persistent dysfunction, elucidation of the underlying molecular
mechanisms, and identification of potential therapeutic targets. Survival and
subsequent patient satisfaction with quality of life have increased. In this
review article, we describe the contributions of the Galveston P50 RCIPS that
have changed postburn care and have considerably reduced postburn mortality.
PMID- 28697017
TI - Risk factors for deep vein thrombosis and pulmonary embolism after traumatic
injury: A competing risks analysis.
AB - BACKGROUND: Venous thromboembolism, including deep vein thrombosis (DVT) and
pulmonary embolism (PE), is typically reported as a composite measure of the
quality of trauma center care. Given that recent data suggesting postinjury DVT
and PE are distinct clinical processes, a better understanding may result from
analyzing them as independent, competing events. Using competing risks analysis,
we evaluated our hypothesis that the risk factors and timing of postinjury DVT
and PE are different. METHODS: We examined all adult trauma patients admitted to
our Level I trauma center from July 2006 to December 2011 who received at least
one surveillance duplex ultrasound of the lower extremities and who were at high
risk or greater for DVT. Outcomes included DVT and PE events, and time-to-event
from admission. We used competing risks analysis to evaluate risk factors for DVT
while accounting for PE as a competing event, and vice versa. RESULTS: Of 2,370
patients, 265 (11.2%) had at least one venous thromboembolism event, 235 DVT
only, 19 PE only, 11 DVT and PE. Within 2 days of admission, 38% of DVT cases had
occurred compared with 26% of PE. Competing risks modeling of DVT as primary
event identified older age, severe injury (Injury Severity Score, >= 15),
mechanical ventilation longer than 4 days, active cancer, history of DVT or PE,
major venous repair, male sex, and prophylactic enoxaparin and prophylactic
heparin as associated risk factors. Modeling of PE as the primary event showed
younger age, nonsevere injury (Injury Severity Score, < 15), central line
placement, and prophylactic heparin as relevant factors. CONCLUSION: The risk
factors for PE and DVT after injury were different, suggesting that they are
clinically distinct events that merit independent consideration. Many DVT events
occurred early despite prophylaxis, bringing into question the preventability of
postinjury DVT. We recommend trauma center quality reporting program measures be
revised to account for DVT and PE as unique events. LEVEL OF EVIDENCE:
Epidemiologic, level III.
PMID- 28697018
TI - The renaissance man of burn surgery: Basil A. Pruitt Jr.
AB - : Dr. Basil A. Pruitt Jr., a consummate clinical and translational surgeon
scientist, has been spent over half a century at the forefront of an advancing
standard of burn care. Commanding the US Army Institute for Surgical Research in
San Antonio, he trained generations of leading burn clinicians and allied
scientists. At his direction, there were forged discoveries in resuscitation from
shock, treatment of inhalation injury, control of burn-related infections,
prevention of iatrogenic complications, and understanding the sympathetic,
endocrine, and immune responses to burn injury. Most consequentially, this team
was among the first recognize and define alterations in the basal metabolic rate
and thermoregulation consequent to burn injury. These investigations prompted
groundbreaking insights into the coordinated nervous, autonomic, endocrine,
immune, and metabolic outflows that a severely-burned patient uses to remain
alive and restore homeostasis. Marking his scientific consequence, many of his
reports continue bear fruit when viewed through a contemporary lens. This paper
summarizes some of the major findings of his career thus far, and is intended to
complement a Festschrift recently held in his honor. LEVEL OF EVIDENCE: Not
applicable.
PMID- 28697019
TI - Outcome differences in adolescent blunt severe polytrauma patients managed at
pediatric versus adult trauma centers.
AB - BACKGROUND: Previous research suggests adolescent trauma patients can be managed
equally effectively at pediatric and adult trauma centers. We sought to determine
whether this association would be upheld for adolescent severe polytrauma
patients. We hypothesized that no difference in adjusted outcomes would be
observed between pediatric trauma centers (PTCs) and adult trauma centers (ATCs)
for this population. METHODS: All severely injured adolescent (aged 12-17 years)
polytrauma patients were extracted from the Pennsylvania Trauma Outcomes Study
database from 2003 to 2015. Polytrauma was defined as an Abbreviated Injury Scale
(AIS) score >=3 for two or more AIS-defined body regions. Dead on arrival,
transfer, and penetrating trauma patients were excluded from analysis. ATC were
defined as adult-only centers, whereas standalone pediatric hospitals and adult
centers with pediatric affiliation were considered PTC. Multilevel mixed-effects
logistic regression models assessed the adjusted impact of center type on
mortality and total complications while controlling for age, shock index, Injury
Severity Score, Glasgow Coma Scale motor score, trauma center level, case volume,
and injury year. A generalized linear mixed model characterized functional status
at discharge (FSD) while controlling for the same variables. RESULTS: A total of
1,606 patients met inclusion criteria (PTC: 868 [54.1%]; ATC: 738 [45.9%]), 139
(8.66%) of which died in-hospital. No significant difference in mortality
(adjusted odds ratio [AOR]: 1.10, 95% CI 0.54-2.24; p = 0.794; area under the
receiver operating characteristic: 0.89) was observed between designations in
adjusted analysis; however, FSD (AOR: 0.38, 95% CI 0.15-0.97; p = 0.043) was
found to be lower and total complication trends higher (AOR: 1.78, 95% CI 0.98
3.32; p = 0.058) at PTC for adolescent polytrauma patients. CONCLUSION: Contrary
to existing literature on adolescent trauma patients, our results suggest
patients aged 12-17 presenting with polytrauma may experience improved overall
outcomes when managed at adult compared to pediatric trauma centers. LEVEL OF
EVIDENCE: Epidemiologic study, level III.
PMID- 28697020
TI - Good news, bad news: An analysis of 11,294 gunshot wounds (GSWs) over two decades
in a single center.
AB - INTRODUCTION: Gun violence is a substantial public health problem accounting for
significant physical, psychological, and financial costs. Although aggregate data
sources demonstrate decreasing rates of firearm violence, analyses from
individual trauma centers have shown that mortality and injury severity from
gunshot wounds (GSWs) are increasing. To evaluate the evolving characteristics of
gun violence in our region, we studied all GSWs admitted to our trauma center
over a 20-year period. METHODS: A retrospective analysis of all newly admitted
patients with GSWs was performed from 1996 to 2016. Our trauma registry was used
to collect data on demographics, mortality, injury severity, body regions
injured, and geographic location of injury. Homicide data were obtained from
local law enforcement. RESULTS: A total of 11,294 patients with GSWs were
reviewed. The number of GSWs treated per biennium increased from 1,349 in 1996
1997 to 1,484 in 2014-2015, with a 59% increase occurring from 2010-2011 to 2014
2015. Overall mortality was 14.6% and decreased from 15.8% in 1996-1997 to 10.2%
in 2014-2015 (p < 0.0001). Mean Injury Severity Score was 12.6 and the percentage
of patients who suffered GSWs to >=3 Abbreviated Injury Scale body regions
increased from 2.5% in 1996-1997 to 7.7% in 2014-2015 (p < 0.0001). Local firearm
homicide data show a 118% increase from 2010 to 2016. CONCLUSIONS: In contrast to
other recent studies, we found that mortality decreased whereas the number of
patients treated for GSWs and those with multicompartmental injuries increased.
The decrease in mortality suggests improved trauma systems as well as an increase
in nonfatal GSWs that dilutes overall mortality. Wounding in multiple body
regions suggests more effective weaponry, including increased magazine size. The
recent increase in local homicides parallels trends in registry data and
illustrates worsening gun violence in our region. Further research is needed to
understand local and regional determinants of increased gun violence to better
guide prevention strategies. LEVEL OF EVIDENCE: Epidemiological study, level III.
PMID- 28697021
TI - Injuries sustained during contact with law enforcement: An analysis from US
trauma centers.
AB - BACKGROUND: Injuries sustained by civilians from interaction with police are a
polarizing contemporary sociopolitical issue. Few comprehensive studies have been
published using national hospital-based data. The aim of this study was to
examine the epidemiology of these injuries to better understand this mechanism of
injury. METHODS: Patients entered into the National Trauma Data Bank (NTDB)
(January 2007 to December 2012) with E-codes E970.0 to E976.0 (International
Classification of Diseases, Ninth Revision, Clinical Modification), identifying
injuries associated with law enforcement in the course of legal action, were
enrolled. Patients' demographics, injury characteristics, procedures, and
outcomes were collected and analyzed. Patients injured by other civilians (E960.0
E968.0) were used for comparison. RESULTS: Of 4,146,428 patients in the NTDB,
7,203 (0.17%) were injured during interaction with police. The numbers of
patients in consecutive study years were 858, 1,103, 1,148, 1,274, 1,316, and
1,504. The incidence of these injuries was stable over time (0.17-0.18%) (p =
0.129). Patients had a median age of 31 years (range, 0-108), and 94.3% were
male. Median injury severity score was 9 (interquartile range [IQR], 4-17). The
most common mechanism of injury was gunshot wound (44%).Patients were white, 43%;
black, 30%; Hispanic, 17%; Asian, 1%; and Other, 9%. As a proportion of the total
race-specific NTDB trauma population, there was an average of 1.13 white
patients, 2.71 Hispanic patients, and 3.83 black patients per 1,000. Mechanism,
injury severity score, and outcomes did not vary by race. Compared to patients
injured by civilians, patients injured by police are more likely to be white (43%
vs 25%, p < 0.001) and injured by gunshot wounds (44% vs 32%, p < 0.001).
CONCLUSIONS: Based on data from trauma centers across the United States, the rate
of injuries sustained during interactions with police has been stable over time.
Gunshot wounds are the most common mechanism of injury. Proportionally, black
patients are the most frequently injured race. When compared to patients injured
by civilians, however, patients injured by police are more likely to be white.
This study provides a step toward a better understanding of police-associated
injuries. LEVEL OF EVIDENCE: Prognostic/epidemiologic study, level III.
PMID- 28697022
TI - An examination of traffic-related traumatic injuries among children at a Level-1
pediatric trauma center, 2005-2014.
AB - BACKGROUND: Traffic-related injuries are the leading fatal injury among children
in the United States, but no published study compares the different types of
traffic-related pediatric injuries to date. Thus, this study was aimed at
examining the10-year trend of traffic-related injury among children at a
pediatric hospital and to assess if there were differences in injury mechanism.
METHODS: All data were drawn from a Level-1 pediatric trauma center in North
Texas in 2005-2014. Demographic characteristics, length of hospitalization, and
patient type were included. Severity of injury outcome was assessed by injury
severity score and fatality. The traffic-related injury mechanism included motor
vehicle collision (MVC), motor-pedestrian collision (MPC), and motorcycle/moped
collision (MMC). Description analyses and multinominal logistic regressions were
applied to examine the factors associated with the type of motor-related injuries
adjusting for covariates. All analyses were conducted by STATA version 14.0.
RESULTS: A total of 3,742 traffic-related pediatric injuries were identified. The
mean (SD) age was 6.4 (4.0) years; most patients were boys (59%) and Hispanic
(40%). There was a waving trend of the number of traffic-related injuries over
the 10-year period. Compared with MVC, demographic disparities exist with
children experiencing an MPC injury. Hispanic and African American children were
more likely to have an MPC but less likely to have a motorcycle/moped collision
injury (relative risk [RR], 1.6; 95% confidence interval, 1.3-1.9; RR, 2.0; 95%
confidence interval, 1.9-2.4, respectively). Children with an MPC injury had a
more severe outcome than those with an MVC injury, but no difference was found in
fatality. The MCC injuries did not significantly differ from MVC in injury
severity. CONCLUSIONS: Although efforts have been made to prevent MVC-related
pediatric injuries, the trend of MVCs was stable in the most recent years. The
MPC-related injury continues to be a higher likelihood of severe pediatric
trauma. Thus, continuing efforts and innovative intervention programs are still
needed to prevent traffic-related pediatric injuries. LEVEL OF EVIDENCE:
Epidemiologic study, level III.
PMID- 28697025
TI - REBOA for the IVC? Resuscitative balloon occlusion of the inferior vena cava
(REBOVC) to abate massive hemorrhage in retrohepatic vena cava injuries.
AB - BACKGROUND: The use of resuscitative endovascular balloon occlusion as a maneuver
for occlusion of the aorta is well described. This technique has life-saving
potential in other cases of traumatic hemorrhage. Retrohepatic inferior vena cava
(IVC) injuries have a high rate of mortality, in part, due to the difficulty in
achieving total vascular isolation. The purpose of this study was to investigate
the ability of resuscitative balloon occlusion of the IVC to control suprahepatic
IVC hemorrhage in a swine model of trauma. METHODS: Thirteen swine were randomly
assigned to control (seven animals) versus intervention (six animals). In both
groups, an injury was created to the IVC. Hepatic inflow control was obtained via
clamping of the hepatoduodenal ligament and infrahepatic IVC. In the intervention
group, suprahepatic IVC control was obtained via a resuscitative balloon
occlusion of the IVC placed through the femoral vein. In the control group, no
suprahepatic IVC control was established. Vital signs, arterial blood gases, and
lactate were monitored until death. Primary end points were blood loss and time
to death. Lactate, pH, and vital signs were secondary end points. Groups were
compared using the chi and the Student t test with significance at p < 0.05.
RESULTS: Intervention group's time to death was significantly prolonged: 59.3 +/-
1.6 versus 33.4 +/- 12.0 minutes (p = 0.001); and total blood loss was
significantly reduced: 333 +/- 122 vs 1,701 +/- 358 mL (p = 0.001). In the
intervention group, five of the six swine (83.3%) were alive at 1 hour compared
to zero of seven (0%) in the control group (p = 0.002). There was a trend toward
worsening acidosis, hypothermia, elevated lactate, and hemodynamic instability in
the control group. CONCLUSIONS: Resuscitative balloon occlusion of the IVC
demonstrates superior hemorrhage control and prolonged time to death in a swine
model of liver hemorrhage. This technique may be considered as an adjunct to
total hepatic vascular isolation in severe liver hemorrhage and could provide
additional time needed for definitive repair. LEVEL OF EVIDENCE: Therapeutic
study, level II.
PMID- 28697026
TI - Smartphone-based mobile thermal imaging technology to assess limb perfusion and
tourniquet effectiveness under normal and blackout conditions.
AB - BACKGROUND: Over the past decade, there has been a resurgence of tourniquet use
in civilian and military settings. Several key challenges include assessment of
limb perfusion and adequacy of tourniquet placement, particularly in the austere
or prehospital environments. We investigated the utility of thermal imaging to
assess adequacy of tourniquet placement. METHODS: The FLIR ONE smartphone-based
thermal imager was utilized. Ten swine underwent tourniquet placement with no
associated hemorrhage (n = 5) or with 40% hemorrhage (n = 5). Experiment 1
simulated proper tourniquet application, experiment 2 had one of two tourniquets
inadequately tightened, and experiment 3 had one of two tourniquets inadequately
tightened while simulating blackout-combat conditions. Static images were taken
at multiple time points up to 30 minutes. Thermal images were then presented to
blinded evaluators who assessed adequacy of tourniquet placement. RESULTS: The
mean core temperature was 38.3 degrees C in non-hemorrhaged animals versus 38.2
degrees C in hemorrhaged animals. Hemorrhaged animals were more hypotensive (p =
0.001), anemic (p < 0.001), vasodilated (p = 0.008), and had a lower cardiac
output (p = 0.007) compared to non-hemorrhaged animals. The thermal imaging
temperature reading decreased significantly after proper tourniquet placement in
all animals, with no difference between hemorrhaged and non-hemorrhaged groups at
30 minutes (p = 0.23). Qualitative thermal image analysis showed clearly visible
perfusion differences in all animals between baseline, adequate tourniquet, and
inadequate tourniquet in both hemorrhaged and non-hemorrhaged groups. Ninety
eight percent of blinded evaluators (n = 62) correctly identified adequate and
inadequate tourniquet placement at 5 minutes. Images in blackout conditions
showed no adverse impact on thermal measurements or in the ability to accurately
characterize perfusion and tourniquet adequacy. CONCLUSIONS: A simple handheld
smartphone-based forward looking infrared radiometry device demonstrated a high
degree of accuracy, reliability, and ease of use for assessing limb perfusion.
Forward looking infrared radiometry also allowed for rapid and reliable
identification of adequate tourniquet placement that was not affected by major
hemorrhage or blackout conditions.
PMID- 28697027
TI - Impact of venous thromboembolism chemoprophylaxis on postoperative hemorrhage
following operative stabilization of spine fractures.
AB - BACKGROUND: Prophylactic anticoagulation may decrease the risk of venous
thromboembolism (VTE) in patients with spine fractures following blunt trauma but
comes with the threat of postoperative bleeding in patients requiring
stabilization of these fractures. The purpose of this study was to evaluate the
impact of preoperative anticoagulation on VTE and bleeding complications in
patients with blunt spine fractures requiring operative stabilization. METHODS:
All patients with blunt spine fractures requiring operative stabilization over a
6-year period were identified. Patients with a hospital stay of less than 48
hours or missing data were excluded. Patients were stratified by age; severity of
shock, spinal cord injury, fracture location, injury severity; and timing and
duration of anticoagulation. Outcomes included bleeding complications (wound
hematoma/infection and development of epidural hematoma) and VTE (pulmonary
embolism and deep venous thrombosis). Outcomes were evaluated to determine risk
factors for bleeding complications and VTE in the management of operative spine
fractures. RESULTS: Seven hundred five patients were identified: 355 patients
received one dose or more of preoperative anticoagulation, and 350 did not
receive preoperative anticoagulation. Seventy-two percent were male, with a mean
injury severity score and Glasgow Coma Scale score of 21 and 14, respectively.
Bleeding complications occurred in 18 patients (2.6%), and 20 patients (2.8%) had
VTE. Patients with VTE were more severely injured (Glasgow Coma Scale score of 13
vs 15, p <= 0.001 and injury severity score of 27 vs 18, p = 0.008). Despite
longer time to mobilization (4 vs 2 days, p < 0.001), patients who received 50%
or more of their scheduled preoperative doses had fewer episodes of pulmonary
embolism (0.4% vs 2.2%, p < 0.05), with no difference in bleeding complications
(2.1% vs 2.9%, p = 0.63) compared to patients who received either no preoperative
anticoagulation or less than 50% of their scheduled preoperative doses.
CONCLUSIONS: Preoperative anticoagulation in patients with operative spine
fractures reduced the risk of pulmonary embolism without increasing bleeding
complications. Preoperative anticoagulation is both safe and beneficial in
patients with operative spine fractures. LEVEL OF EVIDENCE: Therapeutic study,
level IV.
PMID- 28697028
TI - Sciatic (Popliteal Fossa) Catheter for Pediatric Pain Management of Sickle Cell
Crisis: A Case Report.
AB - Sickle cell crisis, or vaso-occlusive crisis (VOC), is a major cause of
hospitalizations for adults and children with sickle cell disease, and is
associated with increased morbidity and mortality. Despite prompt pharmacological
treatment and multimodal pain management, acute pain during a VOC is often not
adequately controlled in the pediatric population. We placed a continuous
popliteal sciatic nerve block under ultrasound guidance in a pediatric patient
for localized refractory pain during a VOC, resulting in improved pain control
with preserved sensorimotor function.
PMID- 28697029
TI - Malignant Hyperthermia in a Morbidly Obese Patient Depletes Community Dantrolene
Resources: A Case Report.
AB - During resection of a duodenal carcinoid tumor, a 28-year-old morbidly obese
woman developed suspected malignant hyperthermia. This hypermetabolic state posed
a diagnostic challenge given the similar intraoperative presentation of carcinoid
crisis and malignant hyperthermia. The patient's weight posed therapeutic
challenges as massive doses and prolonged administration of dantrolene were
required that quickly depleted the available supply. Current dantrolene dosing
recommendations are based on actual body weight despite a paucity of literature
in obese patients. We speculate that the prolonged need for dantrolene redosing
was from the continuous release of the volatile anesthetic from the patient's
adipose tissue.
PMID- 28697030
TI - Severe Postpartum Headache and Hypertension Caused by Reversible Cerebral
Vasoconstriction Syndrome: A Case Report.
AB - Reversible cerebrovascular vasoconstriction syndrome is an uncommon condition
that presents as severe headache and hypertension. Recent literature suggests a
1% incidence in postpartum headache cases. It can cause subarachnoid hemorrhages,
cerebral ischemia, and seizures. It is often misdiagnosed as postdural puncture
headache or preeclampsia. In this case, a postpartum woman, who had received
epidural anesthesia for labor, presented 5 days postpartum with severe headache
that did not resolve with an epidural blood patch. She then became more
hypertensive and suffered a grand mal seizure. When treatment for eclampsia
failed to resolve her symptoms, magnetic resonance angiography was performed. It
demonstrated the pathognomic signs of reversible cerebrovascular vasoconstriction
syndrome. Her symptoms resolved with nimodipine.
PMID- 28697031
TI - Epidural Injections Contraindicated for Lumbar Radiculopathy in May-Thurner
Syndrome: A Case Report.
AB - A 59-year-old patient presented to the chronic pain clinic with a 6-week history
of worsening lumbar back pain, bilateral thigh pain, and unilateral
radiculopathy. Magnetic resonance imaging revealed mild discogenic and
facetogenic disease, but significant epidural venous plexus engorgement
compressing the thecal sac. The patient reported previous treatment by a vascular
surgeon for May-Thurner Syndrome, a type of inferior vena caval obstruction, yet
had not experienced these specific complaints. A discussion with the radiologist
confirmed worsening of the patient's May-Thurner Syndrome was the likely cause of
the patient's symptoms. The patient was referred back to the surgeon to relieve
the venous obstruction because routine injection therapy would be ineffective.
PMID- 28697032
TI - Genicular Radiofrequency Ablation for Treatment of Post Total Knee Arthroplasty
Posterior Thigh Pain: A Case Report.
AB - We present a case of a 68-year-old woman with 6 months of chronic unilateral
posterior thigh pain after a total knee arthroplasty. The patient's pain was
refractory to various treatments. After appropriate diagnostic tests, a genicular
nerve block and subsequent radiofrequency ablation were performed. These
procedures provided substantial pain relief of her thigh pain at 3 months follow
up.
PMID- 28697033
TI - Ventricular Perforation During Open Surgical Balloon Expandable Mitral Valve
Replacement: A Case Report.
AB - A 79-year-old woman with severe mitral annular calcification was scheduled for
mitral valve replacement. A SAPIEN 3 valve was implanted in mitral position using
an open surgical approach. Immediately after cardiopulmonary bypass, bleeding
from an unidentified source was encountered. Cardiopulmonary bypass was
emergently resumed and a laceration of the left ventricular apex due to the valve
delivery system was detected. Risk factors specific to the open surgical approach
include a decompressed ventricle, decreased annulus to apical distance, and the
absence of continuous fluoroscopic and echocardiographic imaging. These create a
clinical scenario where risk of ventricular perforation is increased compared
with traditional intravascular transcatheter valve delivery.
PMID- 28697034
TI - Iatrogenic Endotracheal Tube Obstruction by Tegaderm.
PMID- 28697035
TI - Caring for the lesbian patient at midlife and beyond.
AB - Clinicians who have an understanding of lesbian women and their unique stressors,
who provide a welcoming and inclusive environment, and who provide cross-cultural
care are well positioned to reduce healthcare stigma and improve clinical
outcomes. This Practice Pearl addresses these issues, focusing on the lesbian
patient at midlife and beyond.
PMID- 28697036
TI - Comparison of clinical outcomes among users of oral and transdermal estrogen
therapy in the Women's Health Initiative Observational Study.
AB - OBJECTIVE: To examine associations of estrogen preparations with an index of
health risks versus benefits. METHODS: Using data from 45,112 participants of the
Women's Health Initiative Observational Study (average follow-up 5.5 years), we
examined associations of estrogen type and oral conjugated equine estrogen (CEE)
dose with time to first global index event (GIE), defined as coronary heart
disease, breast cancer, stroke, pulmonary embolism, hip fracture, colorectal
cancer, endometrial cancer, or death. RESULTS: Oral CEE less than 0.625 mg/d +
progestogen (P) users had a lower risk of a GIE (adjusted hazard ratio 0.74, 95%
confidence interval 0.56-0.97) than oral CEE 0.625 mg/d + P users. GIE risk in
oral CEE 0.625 mg/d + P users was greater with at least 5-year use (adjusted
hazard ratio 1.22, 95% confidence interval 1.06-1.41) than with less than 5-year
use. In women with prior hysterectomy, compared with women taking oral CEE 0.625
mg/d for less than 5 years, GIE risk was similar with oral CEE below 0.625 mg/d,
oral estradiol (E2), and transdermal E2, whether used for less than 5 years or
for at least 5 years. There was no difference in GIE risk between users of the
following: oral CEE + P versus oral E2 + P; oral CEE + P versus transdermal E2 +
P; oral E2 + P versus transdermal E2 + P. Findings were similar among women with
hysterectomy taking estrogen alone. CONCLUSIONS: The summary index of risks
versus benefits was similar for oral CEE versus oral or transdermal E2-containing
regimens. CEE + P containing less than 0.625 mg/d of CEE (vs 0.625 mg/d) for less
than 5 years appeared safer.
PMID- 28697037
TI - The association of surgical versus natural menopause with future left ventricular
structure and function: The Coronary Artery Risk Development in Young Adults
(CARDIA) Study.
AB - OBJECTIVE: To evaluate the association between surgical menopause (SM) versus
natural menopause (NM) in relation to later left ventricular (LV) structure and
function, while taking into account the LV parameters and other cardiovascular
disease risk factor (CVDRF) levels that predate the menopausal transition.
METHODS: We studied 825 premenopausal women from the Coronary Artery Risk
Development in Young Adults study in 1990 to 1991 (baseline, mean age 32 years)
who later reached menopause by 2010 to 2011 and had echocardiograms at these two
time points. RESULTS: During 20 years of follow-up, 508 women reached NM, whereas
317 underwent SM (34% had bilateral oophorectomy). At baseline, women who later
underwent SM were more likely to be black, younger, have greater parity, and
higher mean values of systolic blood pressure, body mass index, and also lower
mean high-density lipoprotein cholesterol and physical activity than women who
reached NM. No significant differences in LV structure/function were found
between groups. In 2010 to 2011, SM women had significantly higher LV mass, LV
mass/volume ratio, E/e' ratio, and impaired longitudinal and circumferential
strain than NM women. SM women with bilateral oophorectomy had adverse LV
measures than women with hysterectomy with ovarian conservation. Controlling for
baseline echocardiographic parameters and CVDRF in linear regression models
eliminated these differences between groups. Further adjustment for age at
menopause/surgery and hormone therapy use did not change these results.
CONCLUSION: In this study, the adverse LV structure and function observed among
women with SM compared with NM were explained by their unfavorable presurgical
CVDRF profiles, suggesting that premenopausal CVDRF rather than gynecologic
surgery predispose SM women to elevated future cardiovascular disease risk.
PMID- 28697038
TI - Sleep quality and its association with postural stability and fear of falling
among Spanish postmenopausal women.
AB - OBJECTIVE: To analyze the association of sleep quality with postural balance, as
measured with objective stabilometric parameters, and fear of falling (FoF),
among Spanish postmenopausal women. METHODS: In all, 250 women (60 +/- 8 years)
took part in this cross-sectional study. Sociodemographic and anthropometric data
were collected, as well as information concerning history of falls and FoF.
Anxiety and depression were assessed using the Hospital Anxiety and Depression
Scale, and the Pittsburgh Sleep Quality Index was used to analyze sleep quality.
Measurements of sway area (S), velocity (V), and mediolateral (RMSX) and
anteroposterior (RMSY) displacements of the center of pressure were obtained with
a resistive multisensor platform under both eyes-open (EO) and eyes-closed (EC)
conditions to assess postural control. The independent associations of sleep
quality with FoF and postural control were evaluated by multivariate linear and
logistic regressions, respectively, adjusting for potential confounding
variables. RESULTS: SEO was independently associated (adjusted R = 0.073) with
sleep duration (P < 0.001) and subjective sleep quality (P = 0.001), VEO
(adjusted R = 0.156) with daytime dysfunction (P = 0.006) and sleep duration (P =
0.013), RMSXEO (adjusted R = 0.118) with subjective sleep quality (P = 0.005),
and RMSYEO (adjusted R = 0.166) with sleep duration (P = 0.001) and daytime
dysfunction (P = 0.046). Under EC condition, SEC (adjusted R = 0.014) was
independently related with anxiety (P = 0.034), VEC (adjusted R = 0.148) with
daytime dysfunction (P = 0.002) and sleep duration (P = 0.024), RMSXEC (adjusted
R = 0.134) with subjective sleep quality (P < 0.001), and RMSYEC (adjusted R =
0.128) with sleep duration (P = 0.013) and daytime dysfunction (P = 0.033).
Logistic regression showed that time since menopause (P = 0.003), body mass index
(P = 0.001), and anxiety (P < 0.001), unlike sleep quality, were independently
associated with FoF. The effect size of the model was medium (adjusted R= 0.162).
CONCLUSIONS: In Spanish postmenopausal women, sleep duration, subjective sleep
quality, and daytime dysfunction were independent risk factors for worsened
postural stability. FoF, anxiety, time since menopause onset, and body mass
index, unlike sleep quality, were independently associated with poor postural
stability.
PMID- 28697039
TI - Depressive symptoms and weight in midlife women: the role of stress eating and
menopause status.
AB - OBJECTIVE: Obesity is prevalent in midlife women and contributes to poor health
outcomes. Understanding mechanisms leading to weight gain in this population is
of importance for prevention and intervention. The current study investigated the
association between depressive symptoms and weight in midlife women by examining
stress eating as a mediator between depressive symptoms and weight; and menopause
status as a moderator of the associations of depressive symptoms, stress eating,
and weight. METHODS: An archival analysis was performed using data from the
Midlife in the United States II study. The sample consisted of 815 premenopausal
and postmenopausal women. Measures included the Composite International
Diagnostic Interview-Short Form, a coping questionnaire, and body mass index.
RESULTS: Moderated mediation analyses were conducted with ordinary least squares
path analyses using Hayes' PROCESS macro. Controlling for covariates, depressive
symptoms were not directly associated with weight (b = -0.4, 95% confidence
interval [CI] -0.4, 0.1). However, stress eating was a significant mediator
between depressive symptoms and weight (b = 0.3, 95% CI 0.06, 0.3).The mediation
was conditional on menopausal stage (b = 0.2, 95% CI 0.05, 0.4), with depressive
symptoms and stress eating significantly associated in postmenopausal, not
premenopausal women (b = 0.3, 95% CI 0.2, 0.5). CONCLUSIONS: Both stress eating
and menopause status significantly contributed to the depressive symptom-weight
association. Psychosocial factors play an important role in the association
between depressive symptoms and weight, and the results highlight the need to
focus on both behavioral factors, and also menopause status, when identifying who
is at risk for the development of poor weight outcomes.
PMID- 28697040
TI - Navigating the cervical cancer screening guidelines for women aged older than 65
years.
AB - One of the most notable changes stemming from consensus guidance in 2012 is
cessation of cervical cancer screening in low-risk women aged older than 65
years. Despite evidence provided for this recommendation, implementation in
clinical practice can be challenging, with resistance from patients and
providers. This NAMS Practice Pearl reviews data supporting this recommendation
and provides clinicians with confidence as we counsel our patients.
PMID- 28697041
TI - Circulating osteoprotegerin in postmenopausal osteoporotic women: marker of
impaired glucose regulation or impaired bone metabolism.
AB - OBJECTIVE: Osteoprotegerin (OPG) is closely related to insulin resistance and
bone remodeling. However, no studies have examined the role of OPG in
postmenopausal women with coexistent impaired glucose and bone regulation. The
present study investigated the relationship of OPG to glucose homeostasis and
insulin resistance in postmenopausal osteoporotic women with different types of
glucose tolerance. METHODS: In all, 114 postmenopausal osteoporotic women were
divided into three groups according to glucose tolerance status: 51 with normal
glucose tolerance (NGT, group 1), 31 with impaired glucose tolerance (IGT, group
2), and 32 with type 2 diabetes mellitus (DM, group 3). Study participants were
evaluated for metabolic parameters, OPG, Homeostasis Model Assessment of Insulin
Resistance (HOMA-IR), and bone mineral density parameters. RESULTS: The OPG
levels differed significantly across groups and increased from group 1 to group 3
in a continuous fashion (analysis of variance, P < 0.0001). In post-hoc analysis,
OPG was significantly lower in osteoporotic women with NGT, than participants
with IGT and DM (P < 0.05 and P < 0.0001, respectively). OPG was positively
associated with HOMA-IR (P < 0.0001). No association between serum OPG levels and
measures of BMD was observed. In a multiple regression analysis, OPG emerged as
an independent predictor of HOMA-IR even after controlling for age, body mass
index, and creatinine. CONCLUSIONS: OPG is significantly higher in postmenopausal
osteoporotic women with impaired glucose regulation (IGT and DM) than women with
NGT. OPG was independently associated with insulin resistance assessed by HOMA
IR. Thus, measurement of OPG may potentially be considered as a prediabetic state
screening in postmenopausal osteoporotic women.
PMID- 28697042
TI - Factors associated with different symptom domains among postmenopausal Saudi
women in Riyadh, Saudi Arabia.
AB - OBJECTIVE: To determine factors associated with different symptom domains among
postmenopausal Saudi women in Riyadh, Saudi Arabia. METHODS: In a cross-sectional
study, interviews were conducted with 542 postmenopausal Saudi women, comprising
sociodemographic history, social support, and the Menopause-specific Quality of
Life questionnaire. RESULTS: The mean age of participants was 58 (+/-7.0) years,
and the mean age at menopause was 49 (+/-4.7) years. We found that 41% (n = 224),
14.4% (n = 78), 57% (n = 307), and 12.7% (n = 69) of women reported
severe/moderate impact of vasomotor, psychosocial, physical, and sexual symptoms,
respectively. Multivariate logistic regression revealed that lacking emotional
support was associated with severe/moderate vasomotor (adjusted odds ratio [aOR]
1.5, 95% confidence interval [CI] 1.1, 2.3), psychosocial (aOR 2.0, 95% CI 1.2,
3.4), and physical (aOR 1.7, 95% CI 1.2, 2.6) symptoms. Lack of tangible social
support was associated with severe/moderate sexual symptoms (aOR 1.9, 95% CI 1.0,
3.4). In addition, women who worked (aOR 1.8, 95% CI 1.1, 3.2), were obese (aOR
2.0, 95% CI 1.0, 4.1), lived in rented accommodations (aOR 3.9, 95% CI 1.2,
13.1), or had a retired spouse (aOR 1.6, 95% CI 1.0, 2.4) had higher odds for
moderate/severe menopausal symptoms. CONCLUSIONS: Establishing educational and
counseling programs for postmenopausal women, their spouses, and other family
members could improve social support and hence quality of life of postmenopausal
women. Effective preventive strategies to deal with modifiable risk factors, such
as obesity and work stress, should also be implemented.
PMID- 28697043
TI - Vasomotor hot flashes and cardiac repolarization: a randomized placebo-controlled
trial of postmenopausal hormone therapy.
AB - OBJECTIVE: The aim of the study was to compare the effects of different hormone
therapies on cardiac repolarization in recently postmenopausal women with and
without hot flashes. METHODS: We recruited 150 healthy women: 72 with and 78
without hot flashes. They were randomized and treated for 6 months with
transdermal estradiol (1 mg/day), oral estradiol (OE) alone (2 mg/day) or
combined with medroxyprogesterone acetate (MPA; 5 mg/day), or placebo. Cardiac
repolarization was assessed by measuring QT intervals, rate-dependence of QT-end
interval, and T waves from 24-hour electrocardiographic recording before and
during hormone therapy, comprising a total of over 20 million QT-interval
measurements. RESULTS: Hot flashes were accompanied with shortened median T-peak
T-end interval (at RR interval of 700, 800, and 900 ms; P = 0.040, 0.020, and
0.032; eta = 0.35, 0.39, and 0.37; respectively) during the use of OE but not
transdermal estradiol. In contrast, the addition of MPA to OE lengthened the
maximal QT-end (at RR interval of 500 ms, P = 0.016, eta = 0.27) and the maximal
T-peak - T-end interval (at RR interval of 500 and 600 ms; P = 0.016 and 0.032;
eta = 0.25 and 0.22, respectively). These effects were not seen in women without
hot flashes. CONCLUSIONS: Hot flashes predict beneficial shortening in cardiac
repolarization during OE, but not if MPA is combined with OE. These data may
provide one explanation for MPA-related cardiac hazards in epidemiological
studies.
PMID- 28697044
TI - To the Editor.
PMID- 28697045
TI - Patient characteristics, menopause symptoms, and care provided at an
interdisciplinary menopause clinic: retrospective chart review.
AB - OBJECTIVE: The goal of this study was to describe the characteristics, menopause
symptoms, and treatment progressions in women cared for at an interdisciplinary
menopause clinic. METHODS: We conducted a retrospective review of patient charts
from women attending a multidisciplinary menopause clinic. Data collected from
the charts included patient demographics, menopause symptoms, other concurrent
medical conditions, and treatment recommendations. Data were entered into
Research Electronic Data Capture database and analyzed descriptively. Generic
symptom severity questionnaires were used to compare severity scores from initial
to follow-up visits. RESULTS: Among the 198 women (mean age 52.1 y [+/-SD 6.3],
63.6% postmenopausal), the most common moderate/severe menopause symptoms were as
follows: difficulty staying asleep or waking frequently (76.3%), tiredness
(73.7%), and lack of interest in sex (60.1%). Women tended to have complex
chronic medical conditions, with 54.5% suffering from four or more concurrent
medical conditions. The majority of women (70.2%) were recommended various forms
of hormone therapy. Women with a follow-up visit at 3 to 4 months reported a
reduction in symptom severity. CONCLUSIONS: Our study addresses a gap in
published information on patient characteristics and treatment in menopause
specific interdisciplinary clinics. The chart review highlights the variety of
symptom experience and complexity of care faced in a menopause clinic. Rigorous
prospective studies including standardized data collection and follow-up are
needed to help guide clinicians in managing complex menopause patients.
PMID- 28697046
TI - Perimenopausal arthralgia in the shoulder.
AB - OBJECTIVE: To evaluate perimenopausal arthralgia in the shoulder and treatment
thereof. METHODS: Participants with perimenopausal (n = 197) or premenopausal (n
= 113) shoulder arthralgia were included in the study. The prevalences of
synovitis, adhesive capsulitis, rotator cuff disorder, arthritis, and other
pathologies in the two groups were compared. Participants diagnosed with
synovitis were treated with oral prednisolone for 9 to 12 weeks. RESULTS: The
most common diagnosis in the perimenopausal and premenopausal groups was adhesive
capsulitis (35.4% and 31.8%, respectively), but the difference in prevalence
between the two groups was not significant (P = 0.532). The second most common
diagnosis in the perimenopausal group was shoulder synovitis (25.1%), the
prevalence of which was significantly higher than that in the premenopausal group
(6.2%; P < 0.001). An improvement after treatment with oral prednisolone was
reported by 92.9% of the 56 participants diagnosed with shoulder synovitis.
CONCLUSIONS: In this study, we evaluated the relationship between menopause and
shoulder arthralgia, specifically synovitis. These findings can help clinicians
correctly diagnose and treat shoulder arthralgia in perimenopausal women.
PMID- 28697047
TI - Does having children earlier help you see things more clearly?
PMID- 28697048
TI - Impact of age at first childbirth on primary open-angle glaucoma.
AB - OBJECTIVE: No studies have addressed the relationship between the timing of first
childbirth and primary open-angle glaucoma (POAG). The aim of the study was to
identify the relationship between age at first childbirth and POAG and to examine
the contribution of parity to the age at first childbirth-POAG relationship in
postmenopausal women. METHODS: The study population comprised postmenopausal
women aged 50 or above in the cross-sectional Korea National Health and Nutrition
Examination Survey from 2010 to 2012. Participants were grouped into quintiles by
age at first childbirth for analysis. This study used logistic regression and
mediation analyses with accommodations for the complex sampling structure of the
survey. RESULTS: Of the 4,057 women in the study population, the mean age at
first childbirth was 23.7 years, and POAG prevalence was 3.4%. Prevalence of POAG
was lowest in women whose first childbirth was between the ages of 27 and 44
(1.8%). Their risk for POAG (odds ratio [OR], 0.25; 95% CI, 0.10-0.65) was
significantly lower than in those whose first childbirth was between the ages of
13 and 20, after adjustments for covariates. Late first delivery (>=27 y) was
directly (OR, 0.57) and totally (OR, 0.85) associated with the decreased risk of
POAG; decreased parity in women who delivered their first child at an older age
attenuated the age at first childbirth-POAG relationship (OR of indirect effect,
1.50). CONCLUSIONS: First childbirth at the age of 27 years or above decreases
the risk of POAG in postmenopausal women. Decreased parity, caused by late first
childbirth, attenuated the magnitude of the total effects of age at first
childbirth on POAG.
PMID- 28697049
TI - Wide Variation and Overprescription of Opioids After Elective Surgery.
AB - OBJECTIVE: We aimed to identify opioid prescribing practices across surgical
specialties and institutions. BACKGROUND: In an effort to minimize the
contribution of prescription narcotics to the nationwide opioid epidemic,
reductions in postoperative opioid prescribing have been proposed. It has been
suggested that a maximum of 7 days, or 200 mg oral morphine equivalents (OME),
should be prescribed at discharge in opioid-naive patients. METHODS: Adults
undergoing 25 common elective procedures from 2013 to 2015 were identified from
American College of Surgeons National Surgical Quality Improvement Program data
from 3 academic centers in Minnesota, Arizona, and Florida. Opioids prescribed at
discharge were abstracted from pharmacy data and converted into OME. Wilcoxon
Rank-Sum and Kruskal-Wallis tests assessed variations. RESULTS: Of 7651 patients,
93.9% received opioid prescriptions at discharge. Of 7181 patients who received
opioid prescriptions, a median of 375 OME (interquartile range 225-750) were
prescribed. Median OME varied by sex (375 men vs 390 women, P = 0.002) and
increased with age (375 age 18-39 to 425 age 80+, P < 0.001). Patients with
obesity and patients with non-cancer diagnoses received more opioids (both P <
0.001). Subset analysis of the 5756 (75.2%) opioid-naive patients showed the
majority received >200 OME (80.9%). Significant variations in opioid prescribing
practices were seen within each procedure and between the 3 medical centers.
CONCLUSIONS: The majority of patients were overprescribed opioids. Significant
prescribing variation exists that was not explained by patient factors. These
data will guide practices to optimize opioid prescribing after surgery.
PMID- 28697050
TI - Transfusion Requirement in Burn Care Evaluation (TRIBE): A Multicenter Randomized
Prospective Trial of Blood Transfusion in Major Burn Injury.
AB - OBJECTIVE: Our objective was to compare outcomes of a restrictive to a liberal
red cell transfusion strategy in 20% or more total body surface area (TBSA) burn
patients. We hypothesized that the restrictive group would have less blood stream
infection (BSI), organ dysfunction, and mortality. BACKGROUND: Patients with
major burns have major (>1 blood volume) transfusion requirements. Studies
suggest that a restrictive blood transfusion strategy is equivalent to a liberal
strategy. However, major burn injury is precluded from these studies. The optimal
transfusion strategy in major burn injury is thus needed but remains unknown.
METHODS: This prospective randomized multicenter trial block randomized patients
to a restrictive (hemoglobin 7-8 g/dL) or liberal (hemoglobin 10-11 g/dL)
transfusion strategy throughout hospitalization. Data collected included
demographics, infections, transfusions, and outcomes. RESULTS: Eighteen burn
centers enrolled 345 patients with 20% or more TBSA burn similar in age, TBSA
burn, and inhalation injury. A total of 7054 units blood were transfused. The
restrictive group received fewer blood transfusions: mean 20.3 +/- 32.7 units,
median = 8 (interquartile range: 3, 24) versus mean 31.8 +/- 44.3 units, median =
16 (interquartile range: 7, 40) in the liberal group (P < 0.0001, Wilcoxon rank
sum). BSI incidence, organ dysfunction, ventilator days, and time to wound
healing (P > 0.05) were similar. In addition, there was no 30-day mortality
difference: 9.5% restrictive versus 8.5% liberal (P = 0.892, chi test).
CONCLUSIONS: A restrictive transfusion strategy halved blood product utilization.
Although the restrictive strategy did not decrease BSI, mortality, or organ
dysfunction in major burn injury, these outcomes were no worse than the liberal
strategy (Clinicaltrials.gov identifier NCT01079247).
PMID- 28697051
TI - DCIS and Breast Cancer: Challenging the Paradigm.
PMID- 28697052
TI - Response to: "DCIS and Breast Cancer: Challenging the Paradigm".
PMID- 28697053
TI - Postoperative Adjuvant Therapy for Resectable Pancreatic Cancer With Gemcitabine
and Adoptive Immunotherapy.
AB - OBJECTIVES: We previously described adoptive immunotherapy (AIT) with cytotoxic T
lymphocytes (CTLs) stimulated by the mucin 1 (MUC1)-expressing human pancreatic
cancer cell line YPK-1 (MUC1-CTLs) and demonstrated that MUC1-CTLs might prevent
liver metastasis. In the present study, we combined gemcitabine (GEM) and AIT for
the treatment of pancreatic cancer. METHODS: A total of 43 patients who underwent
radical pancreatectomy received treatment with MUC1-CTLs and GEM. After surgery,
MUC1-CTLs were induced and administered intravenously 3 times, and GEM
administered according to the standard regimen for 6 months. The patients whose
relative dose intensity of GEM was 50% or more and who received 2 or more MUC1
CTL treatments were used as the adequate treatment group (n = 21). RESULTS: In
the adequate treatment group, disease-free survival was 15.8 months, and overall
survival was 24.7 months. Liver metastasis was found only in 7 patients (33%),
and local recurrence occurred in 4 patients (19%). The independent prognostic
factor of long-term disease-free survival on multivariate analysis was the
average number of CTLs administered (P = 0.0133). CONCLUSIONS: The combination
therapy with AIT and GEM prevented liver metastasis and local recurrence.
Moreover, the disease free-survival was improved in patients who received
sufficient CTLs.
PMID- 28697054
TI - Medication Simulation Affects Health Provider Students' Attitudes About Adherence
and Concordance.
AB - INTRODUCTION: Assisting polypharmacy patients with complex health regimens is a
part of health provider responsibilities. The concepts of adherence and
concordance contrast the traditional emphasis on patient compliance. However,
health provider students may not be able to empathize with polypharmacy patients.
The purpose of this study was to measure the effect of a medication simulation on
medical, nursing, and pharmacy students' beliefs about adherence and concordance.
METHODS: A prospective, quasi-experimental, pretest, and posttest design was used
with institutional review board approval. The participants (N = 62) took four
simulated medications (varied dosing schedules) for 1 week. Attitudes toward
adherence and concordance were assessed before and after the intervention.
RESULTS: Subjects averaged 24.6 years (SD = 4.32), 72.6% female, and 79% white.
Most were medical students (n = 33, 53%), followed by nursing (n = 21, 34%) and
pharmacy students (n = 8, 13%). There were significant changes [t(61) = 3.92, P <
0.001] in beliefs about adherence from time 1 (mean = 25.13, SD = 5.77) to time 2
(mean = 22.05, SD = 6.06), and about concordance (mean = 41.85, SD = 5.58 time 1)
to (mean = 44.29, SD = 6.32 time 2) [t(61) = 3.31, P < 0.05], for the entire
group. Most students (84%) predicted that they would be able to take four
medications correctly for 1 week. Fifty-eight students (94%) found that adherence
was 'much harder' or 'a little harder' than anticipated. Most (89%) felt that the
simulation will impact their patient care. CONCLUSIONS: Participation in a
medication simulation exercise affected health provider students' attitudes
toward adherence and concordant behaviors. These experiences may influence future
patient interactions.
PMID- 28697055
TI - Development and Assessment of Pictorial Guide for Improved Accuracy of Visual
Blood Loss Estimation in Cesarean Delivery.
AB - INTRODUCTION: Estimated blood loss for surgical procedures performed via visual
estimation is known to be an inaccurate method. Blood loss estimation is further
complicated during cesarean delivery (CD) by a large volume loss for a short
period as well as the presence of amniotic fluid. We hypothesized that a
pictorial guide depicting premeasured blood volumes and materials commonly used
in a CD would improve clinician accuracy in estimated blood loss. METHODS: A
simulated CD scene was used to assess the ability of clinicians to estimate the
amount of blood lost by a CD patient. Accuracy of the estimates was assessed
before and after they had access to the pictorial guide created for the study.
RESULTS: Before the intervention, 52% of participants estimated more than 25%
above or below actual blood loss volume. With use of the guide, clinicians became
more accurate at blood loss estimation. After the intervention, the number of
participants estimating within 5% of the actual volume increased from 7% before
to 24% (P = 0.033). CONCLUSIONS: An institution-specific pictorial guide is
effective at improving the accuracy of visual blood loss estimation in a
simulation and may help improve clinical care in CD.
PMID- 28697056
TI - Effect of Emergency Department Mattress Compressibility on Chest Compression
Depth Using a Standardized Cardiopulmonary Resuscitation Board, a Slider Transfer
Board, and a Flat Spine Board: A Simulation-Based Study.
AB - INTRODUCTION: Cardiopulmonary resuscitation (CPR) performed on a mattress
decreases effective chest compression depth. Using a CPR board partially
attenuates mattress compressibility. We aimed to determine the effect of a CPR
board, a slider transfer board, a CPR board with a slider transfer board, and a
flat spine board on chest compression depth with a mannequin placed on an
emergency department mattress. METHODS: The study used a cross-over study design.
The CPR-certified healthcare providers performed 2 minutes of compressions on a
mannequin in five conditions, an emergency department mattress with: (a) no hard
surface, (b) a CPR board, (c) a slider transfer board, (d) a CPR board and slider
transfer board, and (e) a flat spine board. Compression depths were measured from
two sources for each condition: (a) an internal device measuring sternum-to-spine
compression and (b) an external device measuring sternum-to-spine compression
plus mattress compression. The difference of the two measures (ie, depleted
compression depth) was summarized and compared between conditions. RESULTS: A
total of 10,203 individual compressions from 10 participants were analyzed. The
mean depleted compression depths (percentage depletion) secondary to mattress
effect were the following: 23.6 mm (29.7%) on a mattress only, 13.7 mm (19.5%) on
a CPR board, 16.9 mm (23.1%) on a slider transfer board, 11.9 mm (17.3%) on a
slider transfer board plus backboard, and 10.3 mm (15.4%) on a flat spine board.
The differences in percentage depletion across conditions were statistically
significant. CONCLUSION: Cardiopulmonary resuscitation providers should use a CPR
board and slider transfer board or a flat spine board alone because these
conditions are associated with the smallest amount of mattress compressibility.
PMID- 28697057
TI - Computerized Virtual Reality Simulation in Preclinical Dentistry: Can a
Computerized Simulator Replace the Conventional Phantom Heads and Human
Instruction?
AB - STATEMENT: In preclinical dental education, the acquisition of clinical,
technical skills, and the transfer of these skills to the clinic are paramount.
Phantom heads provide an efficient way to teach preclinical students dental
procedures safely while increasing their dexterity skills considerably. Modern
computerized phantom head training units incorporate features of virtual reality
technology and the ability to offer concurrent augmented feedback. The aims of
this review were to examine and evaluate the dental literature for evidence
supporting their use and to discuss the role of augmented feedback versus the
facilitator's instruction. Adjunctive training in these units seems to enhance
student's learning and skill acquisition and reduce the required faculty
supervision time. However, the virtual augmented feedback cannot be used as the
sole method of feedback, and the facilitator's input is still critical. Well
powered longitudinal randomized trials exploring the impact of these units on
student's clinical performance and issues of cost-effectiveness are warranted.
PMID- 28697058
TI - Accuracy of a Single Item on Mentally Tiring Work as Proxy Measure of Job Demands
and Efforts in the Gazel Cohort.
PMID- 28697059
TI - Associations Between Age, Psychosocial Work Conditions, Occupational Well-Being,
and Telomere Length in Geriatric Care Professionals: A Mixed-Methods Study.
AB - OBJECTIVE: We identified associations between age, psychosocial work
characteristics, occupational well-being, and-as a measure of biological age
leukocyte telomere length in geriatric care professionals. METHODS: This is a
multisource study of self-reports on psychosocial work characteristics,
standardized physician's evaluations of health, and relative telomere length
measures of peripheral blood leukocytes. We included 141 geriatric care
professionals. Telomere length was assessed by an improved polymerase chain
reaction (PCR)-based method. RESULTS: Increased depersonalization was associated
with shorter telomeres. Their association with age was not moderated by
psychosocial work conditions. There was, however, a significant three-way
interaction of social support and work ability with the age-telomere association.
Additionally, social support and adverse general health moderated the age
telomere length relationship. CONCLUSIONS: A supportive work environment and work
related health may influence the association between age and telomere length.
PMID- 28697060
TI - Mortality Among Hardmetal Production Workers: UK Cohort and Nested Case-Control
Studies.
AB - OBJECTIVE: The aim of this study was to characterize the mortality at two
hardmetal production factories in the United Kingdom as part of an international
study. METHODS: Standardized mortality ratios (SMRs) were calculated on the basis
of mortality rates for England and Wales, and local rates. A nested case-control
study of lung cancer was undertaken. RESULTS: The cohort comprised 1538 workers,
with tracing complete for 94.4%. All-cause mortality was statistically
significantly low for all cancers and nonmalignant respiratory disease, and for
lung cancer was nonsignificantly low. The SMR for lung cancer for maintenance
workers was elevated, based on only six deaths. The odds ratio for lung cancer
per year of exposure to hardmetal was 0.93 (0.76 to 1.13). CONCLUSIONS: In this
small study, there is no evidence to support that working in the UK hardmetal
manufacturing industry increased mortality from any cause including lung cancer.
PMID- 28697061
TI - Elevation of Circulating Th17/Th22 Cells Exposed to Low-Level Formaldehyde and
Its Relevance to Formaldehyde-Induced Occupational Allergic Contact Dermatitis.
AB - OBJECTIVES: The aim of this study was to investigate the effects of formaldehyde
exposure on Th17 and Th22 cells and its relevance to human occupational allergic
contact dermatitis (OACD). METHODS: Circulating IL17-/IL22-secreting cells and
serum IL17/IL22 levels in formaldehyde-exposed workers at Occupational Exposure
Limit and nonexposed controls were assessed. RESULTS: The IL17 and IL22 cell
population were detected in both CD3CD8 and CD3CD8 cells. The percentages of
circulating IL17 and IL22 T cells in the workers with and without ACD history
were all elevated, which were more remarkable in the ones with ACD history. Serum
levels of IL17 and IL22 between the workers and controls were not significantly
different. CONCLUSIONS: Low-level formaldehyde exposure may increase circulating
IL17-/IL22-producing T cells (CD8 and CD8), possibly involved in the development
of human OACD. But it may not alter serum levels of IL17/IL22 before the
appearance of OACD symptoms.
PMID- 28697062
TI - Morbidity and Health Risk Factors Among New Mexico Miners: A Comparison Across
Mining Sectors.
AB - OBJECTIVE: This study examines differences in chronic health outcomes between
coal, uranium, metal, and nonmetal miners. METHODS: In a cross-sectional study
using data from a health screening program for current and former New Mexico
miners, log-binomial logistic regression models were used to estimate relative
risks of respiratory and heart disease, cancer, osteoarthritis, and back pain
associated with mining in each sector as compared with coal, adjusting for other
relevant risk factors. RESULTS: Differential risks in angina, pulmonary symptoms,
asthma, cancer, osteoarthritis, and back pain between mining sectors were found.
CONCLUSIONS: New Mexico miners experience different chronic health challenges
across sectors. These results demonstrate the importance of using comparable data
to understand how health risks differ across mining sectors. Further
investigation among a broader geographic population of miners will help identify
the health priorities and needs in each sector.
PMID- 28697063
TI - Disseminating Pesticide Exposure Results to Farmworker and Nonfarmworker Families
in an Agricultural Community: A Community-Based Participatory Research Approach.
AB - OBJECTIVE: The aim of this study was to examine the impact of a dissemination
process to provide individual pesticide results to study participants. METHODS:
After working with community members to disseminate data, 37 participants were
recontacted via an interview survey to assess the effectiveness of the
dissemination process. RESULTS: Almost all participants (97.3%) recalled a home
visit from a health promoter; 29 (78.4%) correctly recalled that the health
promoter used a thermometer or graphic to explain the results; 26 (70.3%)
correctly interpreted graphics showing high and low exposure levels in adults and
75.7% correctly interpreted results for children. CONCLUSIONS: The study results
support the use of a community-based participatory research approach to decide
how to best depict and disseminate study results, especially among participants
who are often left out of the dissemination process.
PMID- 28697064
TI - Quality Control in Modern Immunohistochemistry: Real-time Performance
Characteristics and Quality Control of Important Widely Used Antibodies.
PMID- 28697065
TI - Accurate PD-L1 Protocols for Non-Small Cell Lung Cancer can be Developed for
Automated Staining Platforms With Clone 22C3.
AB - Treatment using immunotherapy against PD-L1 or PD-1 has become one of the hottest
topics in Pathology and Oncology. Correct selection of patients eligible for
treatment requires optimal immunohistochemical staining protocols. Treatment with
pembrolizumab requires diagnostic examination of the patient's tumour using the
companion diagnostic Ready-To-Use pharmDx kit from Dako Agilent based on the mAb
22C3 clone on the Autostainer platform. However, not all diagnostic pathology
labs have access to this staining platform. This purpose of this study was to
develop and validate protocols for PD-L1 detection for all major staining
platforms using the concentrated format of 22C3 that would give similar staining
result (equal Tumour Proportion Scores) to the pharmDx kit.
PMID- 28697066
TI - Viral-induced Modulation of Multiple Checkpoint Proteins in Cancers.
AB - Therapy with checkpoint inhibitors represents a major advance in cancer
treatment. The purpose of this study was to examine the expression patterns of
the checkpoint proteins programmed death ligand 1 (PD L1), PD L2, indoleamine 2,3
dioxygenase 1 (IDO1), and cytotoxic T-lymphocyte antigen 4 (CTLA4) in cancers
including those associated with viral infections. Normal, noninflamed tissues
rarely express checkpoint proteins with exceptions including the placenta and
stomach. Expression of PD L1 was noted in 30%, PD L2 in 18%, IDO1 in 13%, and
CTLA4 in 14% of 333 nonviral malignancies including endometrial, ovarian, lung,
and breast cancers. The expression of each checkpoint protein was significantly
higher among 166 cases of viral-related (mostly human papillomavirus) cancers
where expression of PD L1 was noted in 84%, PD L2 in 67%, IDO1 in 61%, and CTLA4
in 37% (each P value <0.001); 97% of the viral-related cancers showed expression
of at least 1 checkpoint protein. In addition, over 90% of the CD8 cells in the
viral-associated cancers were quiescent based on low coexpression of Ki-67 as
well as pSTAT1. It is concluded that viral infection in cancers is associated
with the increased expression of key checkpoint proteins. This indicates that
cancers with productive viral infection may be better targets for checkpoint
inhibitor therapy.
PMID- 28697067
TI - Introduction.
PMID- 28697068
TI - Intraoperative Video Production With a Head-Mounted Consumer Video Camera.
AB - The use of high-definition video in surgical education is becoming increasingly
popular. Because of the availability of relatively inexpensive, consumer-grade
video cameras, surgeons with minimal video production experience can produce high
quality surgical videos. A number of video capture methods are available, with
varying degrees of production quality, economic constraint, and level of
attention required from the operating surgeon. The accompanying video provides an
overview of the advantages and disadvantages of several options and describes a
technique for capturing intraoperative video with the use of a head-mounted,
consumer video camera.
PMID- 28697069
TI - Suggested Tips and Tricks to Enhance Surgical Video Production.
AB - PURPOSE: Surgical video production is an important skill that can be of valuable
use as an educational tool. However, it is important that surgical videos be
filmed and edited in a methodological way to maximize its potential. In this
video, we describe our preference for producing quality surgical videos. METHODS:
There are many important factors to consider during the filming process,
including vantage point of the videographer, lighting, and visualization of
instruments. During the editing process, certain techniques can be used to make
the video more stimulating and thus more engaging to the viewer. RESULTS: This
video presents the filming and editing of a single case. In addition, we provide
examples of acceptable and poor footage and editing techniques. CONCLUSIONS:
Surgical videos can be a valuable educational tool when properly executed. In
this video, we describe techniques to ensure quality production.
PMID- 28697070
TI - Retrograde Femoral Nailing Using Percutaneous Reduction Techniques.
AB - Femoral shaft fractures are commonly treated with closed reduction and reamed
intramedullary nailing. However, some reductions are difficult to obtain or
maintain, especially in muscular or large patients. When closed methods fail to
achieve reduction, percutaneous techniques are extremely useful. In addition, the
use of either permanent or temporarily placed blocking implants offer a minimally
invasive option for improving sagittal and coronal plane alignment. In the
accompanying video, we describe our method of percutaneous reduction techniques
in the setting of a comminuted femoral shaft fracture treated with a retrograde
femoral intramedullary nail.
PMID- 28697071
TI - ORIF Patella Fracture With a Tension Band Construct.
AB - Patellar fractures can occur as a result of direct or indirect injuries. Indirect
injury is more common and occurs when the patella fails in tension when the force
exerted by the extensor mechanism exceeds that of the bone. Common mechanism of
indirect injury is rapid knee flexion with fully contracted quadriceps muscle.
Treatment with a tension band construct is indicated for transverse patella
fractures without significant comminution. This can be performed with 18-gauge
wire and either 2 parallel, longitudinally oriented cannulated screws or 2
Kirschner wires. Biomechanical studies have shown higher load to failure when
performed with cannulated screws. We presented our technique for management of a
transverse patella fracture with disrupted extensor mechanism using tension
banding technique with cannulated screws.
PMID- 28697072
TI - Repair of Displaced Partial Articular Fracture of the Distal Femur: The Hoffa
Fracture.
AB - PURPOSE: The Hoffa fracture is a rare fracture pattern consisting of a
unicondylar posterior fracture of the distal femur. This video demonstrates a
case of Hoffa fracture repair using headless screw compression. METHODS: Hoffa
fractures are intra-articular in nature. Given that isolated Hoffa fractures are
rare, there is little information available as to the best management of this
injury. However, several small studies have demonstrated good-to-excellent
functional results after anatomical reduction and rigid fixation of the Hoffa
fracture, followed by early mobilization. RESULTS: This video presents a case of
surgical repair of a Hoffa fracture, and contaminant meniscal repair, in a 25
year-old man. Partially threaded, headless compression screws provide for
independent compression of the fracture after placement. CONCLUSIONS: The Hoffa
fracture is a rare injury typically seen after high-energy trauma. The surgical
technique for treatment of the Hoffa fracture as seen in this video provides good
stabilization and enables for early range of motion.
PMID- 28697073
TI - Percutaneous Repair of a Schatzker III Tibial Plateau Fracture Assisted by
Arthroscopy.
AB - PURPOSE: Tibial plateau fractures are articular fractures that sometimes prove
difficult to effectively manage and treat. Although fluoroscopy is frequently
used to assess the articular reduction in the surgical repair of tibial plateau
fractures, this video demonstrates the additional benefit of arthroscopy in
assisting with the articular reconstruction of a Schatzker III tibial plateau
fracture. METHODS: The goal of operative treatment of tibial plateau is
reconstruction of the articular surface followed by reestablishment of tibial
alignment. Arthroscopy has been advocated as a possible supplement to the
operative treatment of tibial plateau fractures. Arthroscopy-assisted fracture
reduction has been shown to provide a significantly improved visualization of
fracture fragment displacement when compared with traditional fluoroscopy use in
select cases. RESULTS: This video demonstrates the use of arthroscopy to
visualize the articular surface and aid in reduction during fixation of a tibial
plateau fracture. Initially, arthroscopic visualization confirms depression of
lateral tibial plateau and the elevation of the fractured segment. After fixation
with 2 partially threaded cancellous screws, arthroscopy confirms articular
reduction and normal relation of lateral meniscus to the articular surface.
CONCLUSIONS: Arthroscopic visualization is a reliable technique for assessing
articular reduction during surgical repair of a tibial plateau fracture. In
addition, this technique enables the surgeon to assess for soft tissue injuries
that could potentially go undiagnosed.
PMID- 28697074
TI - Repair of Bimalleolar Ankle Fracture.
AB - PURPOSE: The incidence of ankle fractures is rapidly increasing in geriatric
populations. Of the 4 fracture patterns described by the Lauge-Hansen
classification system, supination-external rotation (SER) accounts for most ankle
fractures. This video demonstrates surgical repair of a SER type 4 ankle fracture
in a geriatric patient. METHODS: SER type 4 ankle fractures are considered
unstable and are generally treated with surgical fixation. After placement of
plate and screws, intraoperative stress tests can be used to assess for
syndesmotic widening. If necessary, the syndesmosis can be reduced open, with
screw fixation placed parallel to the joint. Patients are kept non-weight-bearing
for 6 weeks after surgery. RESULTS: This video, shot on an iPhone 6S, shows the
case of a 66-year-old female status after a fall with twisting mechanism
resulting in an unstable SER type 4 fracture requiring operative repair.
Intraoperative stress test revealed medial clear space widening requiring
syndesmotic reduction. CONCLUSIONS: SER type 4 ankle fractures are a common
injury that must be properly managed to return patients to baseline functional
status. The surgical technique described in this video provides for good
stabilization and allows for early range of motion with advancement to weight
bearing as tolerated at 6 weeks postoperatively.
PMID- 28697075
TI - Posterolateral Bone Grafting for Distal Tibia Nonunion.
AB - INTRODUCTION: This video demonstrates the technique of posterolateral bone
grafting with iliac crest bone graft for a distal tibial nonunion. METHODS: The
patient is a 42-year-old man who is 6 months status post an open distal tibia
fibula fracture treated surgically, and presents complaints of persistent right
ankle pain. The fracture site was tender to palpation, and 3 consecutive plain
radiographs spaced 6 weeks apart demonstrated no evidence of callus formation.
RESULTS: This patient was indicated for posterolateral bone grafting of his tibia
and fibula nonunion with autogenous iliac crest bone graft. The plan was to
create a synostosis between the fibula and tibia. Atrophic and oligotrophic
nonunions have poor biology at the fracture site to promote bone growth and would
therefore benefit from autogenous iliac bone graft, as this technique is
osteoinductive, osteoconductive, and osteogenic stem cells. Indications for
posterolateral bone grafting of the tibia include atrophic or oligotrophic
nonunions, an ipsilateral same level tibia and fibula nonunion, or a tibial
nonunion with a large anteromedial soft-tissue injury. CONCLUSION: The technique
of posterolateral bone grafting with iliac crest bone graft for distal third
tibia and fibula atrophic nonunion provides a reliable method for achieving
union. If patients with injuries at high risk of nonunion are followed closely
and intervention is performed in a timely manner, additional fixation or revision
of fixation is not necessary if the addition of appropriate osteoinductive,
osteoconductive, and osteogenic material to the nonunion is performed.
PMID- 28697076
TI - Acute Compartment Syndrome of the Leg.
AB - INTRODUCTION: Acute compartment syndrome (ACS) is well known among orthopaedic
surgeons. The timely diagnosis and management of ACS is crucial to avoiding its
sequelae, including renal failure, ischemic contractures, and limb loss. Despite
its relative importance, ACS poses a challenge to many residents and clinicians
as diagnosis relies largely on clinical judgment. METHODS: Timely diagnosis and
thorough compartment release are essential to optimizing outcomes in ACS. This
video highlights a clinical case in which compartment syndrome of the leg was
considered, diagnosed, and surgically managed. RESULTS: This video will present
the indications for compartment release and a video-guided demonstration of
compartment checks using an arterial line transducer, a 4-compartment fasciotomy
with 2 incisions, and temporizing vessel loop closure. CONCLUSIONS: Compartment
syndrome can be a devastating complication of common fractures. It is essential
that orthopaedic practitioners understand the immediacy of intervention. We have
a responsibility to provide timely, accurate diagnosis along with expedient
surgical management.
PMID- 28697077
TI - Femoral Nonunion With Iliac Crest Bone Graft.
AB - PURPOSE: Fracture nonunion is a common problem for today's orthopaedic surgeon.
However, many techniques are currently available for the treatment of long-bone
nonunion. This video demonstrates the use of iliac crest bone graft and plate
stabilization in the setting of a hypertrophic femoral nonunion. METHODS:
Treatment of femoral nonunion after intramedullary nail fixation using
compression plating and bone grafting is a reliable technique for reducing pain,
improving function, and achieving radiographic union. Furthermore, the use of
autologous bone graft, in particular iliac crest bone graft, has provided
reliable clinical results. RESULTS: In this video, we present the case of a
hypertrophic femoral nonunion treated with supplemental bone grafting in addition
to plate and screw fixation. CONCLUSIONS: Although femoral nonunions are a
relatively rare occurrence, they can be reasonably treated using stabilization
and supplemental bone grafting. Iliac crest bone graft provides for excellent
results when used for treatment of a fracture nonunion.
PMID- 28697078
TI - Segmental Bone Defect Treated With the Induced Membrane Technique.
AB - PURPOSE: Posttraumatic bone defects in the setting of severe open injuries of the
lower extremity present a significant challenge for orthopaedic trauma surgeons.
The induced membrane technique, also known as the Masquelet technique, has been
shown to be generally successful in achieving bony union. This video demonstrates
the use of the Masquelet technique for a large (18 cm) femoral defect. METHODS:
The Masquelet technique is a 2-stage process. The first stage involves
debridement of all devitalized tissue, using open reduction and internal
fixation, and placement of a cement spacer with or without antibiotics. In the
second stage, which is performed at least 6 weeks after the first, the spacer is
removed and the resulting void is filled with bone graft. RESULTS: This surgical
case video reviews the relevant patient injury presentation, initial management,
and indications for the Masquelet technique. The second stage of the Masquelet
technique is featured in this video. CONCLUSIONS: The Masquelet technique is a
generally reliable method for treating large segmental bone defects. In addition,
this relatively simple technique is suitable for both infected and noninfected
cases.
PMID- 28697079
TI - Exchange Nailing for Hypertrophic Femoral Nonunion.
AB - Exchange nailing has proven to be a reliable surgical technique for the
management of aseptic femoral shaft nonunions. Similar to primary intramedullary
nail fixation for femur fractures, exchange nailing for aseptic hypertrophic
nonunions of the femur relies on successful navigation of the starting point and
proper nail trajectory to minimize coronal and sagittal plane deformities.
Compared with the supine position, the lateral decubitus position has the
advantage of allowing gravity to displace the soft tissue around the piriformis
start site to facilitate nail entry. In addition, the C-arm position and access
to the affected limb from both sides by the surgeon and surgical assistant
facilitate visualization of existing deformities and the ability to perform
correction maneuvers. The purpose of this review is to highlight technical pearls
associated with exchange nailing in a lateral decubitus position. Although other
techniques are available, and should be used when indicated, exchange nailing
provides patients with the opportunity to an early return to activity,
improvement in pain and disability, and ultimate bony union.
PMID- 28697080
TI - Plate Osteosynthesis of Patella Fractures-A Video Case Report.
AB - Operative management of patella fractures continues to be associated with poor
outcomes and high reoperation rates. Traditionally, tension band fixation has
been used for more simple fracture patterns; however, fixation remains a
challenge particularly for comminuted fractures. More recently, various types of
plate fixation have been used and reported in the literature. Earlier
mobilization after plate osteosynthesis of patella fractures is possible because
of a more robust construct, with the potential for decreased knee stiffness and
improved functional outcomes. We present a video case of a 79-year-old man who
sustained a displaced patella fracture treated with an anterior mesh plate.
PMID- 28697081
TI - Suture Repair of a Pole Patella Fracture.
AB - PURPOSE: Operative fixation of displaced patella fractures is considered to be
standard of care. However, patients with inferior pole patella fractures have
limited options in terms of fixation. This video demonstrates the repair of an
inferior pole patella fracture using nonabsorbable suture fixation. METHODS:
Suture repair of patella fractures is a clinically acceptable technique, yielding
similar functional results to patella fractures treated with K-wires or
cannulated screws while reducing the rates of removal of hardware after fixation.
RESULTS: This video features the repair of a displaced, comminuted inferior pole
patella fracture using 5 Ethibond and Fiberwire. Postoperative radiographs
confirm bony union. CONCLUSIONS: Suture fixation for pole patella fractures
provides reliable fixation and reduces the risk of postoperative complications
secondary to hardware irritation. This case highlights the success of this
technique.
PMID- 28697082
TI - Primary Posterior Blade Plate Tibiotalar Arthrodesis: A Salvage Procedure for
Complex Nonreconstructable Pilon Fractures.
AB - A subset of C2/C3 pilon fractures, open pilon injuries, metaphyseal bone
comminution, and those involving substantial soft tissue or vascular injury may
be nonreconstructable. Such injuries are at risk of progress to nonunion and
failing open reduction internal fixation (ORIF). The risk of infection, malunion,
and nonunion is relatively high with such injury patterns. In such cases,
tibiotalar arthrodesis is performed after ORIF fails as a salvage procedure.
Overall, the literature agrees that all pilon fractures will develop
posttraumatic osteoarthritis, and these patients are ultimately treated with an
arthrodesis or in narrow population with total ankle arthroplasty. Given these
combined findings, it follows that patients identified as high risk of failing
ORIF could benefit from the use of primary arthrodesis. The proposed technique
provides a reliable approach designed to achieve ankle fusion. It provides a
means to achieve reliable union rates and spares the subtalar joint. In addition,
it avoids the anterior soft tissue envelope, and hardware irritation is tempered
as the final implants are covered by a muscular layer. Last, patients who are at
higher risk of failing ORIF are selected and spared, having to undergo trial
ORIF, time to nonunion, work absence, and rehab.
PMID- 28697083
TI - Multiple Rib Nonunion: Open Reduction and Internal Fixation and Iliac Crest Bone
Graft Aspirate.
AB - PURPOSE: Rib fractures are a common chest injury that can typically be treated
nonoperatively. However, a percentage of these will go on to nonunion, either
because of unique characteristics of the fracture itself or because of a variety
of poor healing factors of the host. If a patient has continued symptomology
beyond 3 months, surgeons may consider operative management. METHODS: Although
isolated resection of fibrous scar tissue from the nonunion site may be
sufficient in some cases, it may also be necessary to provide additional
structural integrity to the rib depending on the extent of the fracture pattern
and resection. This goal can be achieved operatively with rib plating and bone
grafting to promote healing. RESULTS: This video demonstrates the use of plating
in the treatment of rib nonunion. It begins with relevant background information
on rib fractures and nonunions, then details the approach, open reduction and
internal fixation of 3 ribs using plates and bone graft aspirate. Pearls and
pitfalls are included during the surgical technique aspect of the video to both
help guide surgeons new to the procedure and provide potentially advantageous
technical details to more experienced surgeons.
PMID- 28697084
TI - Posterior Fracture Dislocation of the Shoulder: A Modified McLaughlin Procedure.
AB - PURPOSE: Bilateral posterior fracture dislocation is a rare injury commonly
associated with seizures. When the humeral head defect (reverse Hill-Sachs
lesion) is between 20% and 45%, operative fixation using a modified McLaughlin
procedure is recommended. This video demonstrates a case of bilateral posterior
fracture dislocation after a drug-induced seizure treated with a modified
McLaughlin procedure. METHODS: The original McLaughlin procedure involved
transfer of the subscapularis tendon from the lesser tuberosity to the reverse
Hill-Sachs defect. However, the modified McLaughlin procedure is more commonly
described in the literature as of late and involved the transfer of the lesser
tuberosity along with the subscapularis. RESULTS: This video demonstrates the
modified McLaughlin technique for a posterior fracture dislocation. Computerized
tomography confirms the articular impression fractures of the proximal humerus.
Through a deltopectoral approach, the lesser tuberosity along with the
subscapularis tendon was transferred into the defect. CONCLUSIONS: The modified
McLaughlin procedure demonstrates excellent clinical and radiographic results
after posterior fracture dislocation of the shoulder with a reverse Hill-Sachs
lesion between 25% and 45%.
PMID- 28697085
TI - Humeral Shaft Fracture: Intramedullary Nailing.
AB - INTRODUCTION: This video demonstrates the technique of intramedullary nailing for
a humeral shaft fracture. METHODS: The patient is a 30-year-old man who sustained
a gunshot wound to his right arm. The patient was indicated for humeral nailing
given the comminuted nature of the diaphysis and to allow for minimal skin
incisions. Other relative indications include soft-tissue compromise about the
arm precluding a large surgical exposure. RESULTS: This video presents a case of
a comminuted humeral shaft fracture treated with an intramedullary nail. Anatomic
reduction and stable fixation was obtained with this technique. CONCLUSION: This
case demonstrates a soft-tissue sparing technique of humeral shaft fixation using
a humeral intramedullary nail. The technique is easy to perform and has
significant benefits in minimizing surgical exposure, decreasing operative time,
and decreasing blood loss. In the correct clinical setting, humeral nailing
provides an expeditious form of fixation that restores length, alignment, and
rotation of the fracture humeral diaphysis.
PMID- 28697086
TI - Use of Volar Plate for Indirect Coronal Plane Reduction in an Intraarticular
Distal Radius Fracture.
AB - Management of intraarticular distal radius fractures requires precise
reconstruction of the articular surface to optimize outcomes. Treatment goals
also include restoration of alignment, rotation, and angulation in both the
coronal and sagittal planes of the metaphyseal component of these fractures.
Surgical management with open reduction and internal fixation with a volar plate
is often the preferred method of open treatment. However, a variety of different
techniques have been described, and the preferred technique may be determined on
an individual basis by the fracture characteristics, patient-dependent factors,
or surgeon experience.
PMID- 28697087
TI - Intramedullary Fixation of Midshaft Clavicle Fractures.
AB - Clavicle fractures are among the most common fractures occurring in the general
population, and the vast majority are localized in the midshaft portion of the
bone. Management of midshaft clavicle fractures remains controversial. Although
many can be managed nonoperatively, certain patient populations and fracture
patterns, such as completely displaced and shortened fractures, are at risk of
less optimal outcomes with nonoperative management; surgical intervention should
be considered in such cases. The purpose of this article is to demonstrate our
technique of midshaft clavicle fixation using minimally invasive intramedullary
fixation.
PMID- 28697088
TI - Intraarticular Distal Radius Fracture Open Reduction Internal Fixation.
AB - PURPOSE: Intraarticular distal radius fractures are often treated with open
reduction and internal fixation (ORIF) through a volar approach. This common
approach, however, is technically demanding to restore the articular surface of
the radiocarpal joint while respecting soft tissue integrity. The purpose of this
video is to demonstrate the surgical technique of volar plate fixation of an
intraarticular distal radius fracture. METHODS: A 32-year-old patient who
sustained multiple injuries including an intraarticular distal radius fracture
was treated with ORIF by a volar approach. RESULTS: Exposure is performed through
a standard flexor carpi radialis approach. The intraarticular fracture of the
distal radius is reduced, and a volar plate is applied. Careful measurement of
screw length is described in detail to minimize postoperative tendon irritation.
Closure of the soft tissues is completed and early postoperative rehabilitation
is emphasized. DISCUSSION: Multiple, varied techniques for fixation of
intraarticular distal radius fractures are described in the literature. As
demonstrated in this video of ORIF with a volar plate, attention to articular
reduction, soft-tissue protection, and postoperative rehabilitation are key
components used to achieve good clinical outcomes.
PMID- 28697089
TI - Fixation of a Proximal Humerus Fracture With an Intramedullary Nail.
AB - Proximal humerus fractures (PHFs) are common injuries seen mostly in elderly
patients. Although nonoperative management is acceptable for most patients,
surgical fixation is often advocated for younger patients or active, elderly
patients with reconstructable fractures. A variety of fixation methods exist:
percutaneous pinning, open reduction and internal fixation with locking plates,
and intramedullary nailing are viable options. Modern intramedullary nails serve
as excellent options for the fixation of many operative PHFs. In this
Supplemental Digital Content 1 (see video, http://links.lww.com/JOT/A27), we
discuss the care of a 63-year-old active, healthy female with a 2-part PHF. The
details of fixation of PHFs using a straight intramedullary nail are included, as
well as a relevant literature review and description of our postoperative
rehabilitation protocol.
PMID- 28697090
TI - Extensile Fasciotomy for Compartment Syndrome of the Forearm and Hand.
AB - PURPOSE: The purpose of this video is to demonstrate the technique of an
extensile fasciotomy of the forearm and hand. METHODS: A patient presented to our
hospital with a rapidly progressing infection of the right upper extremity and
clinical signs and symptoms of compartment syndrome. The patient was immediately
taken to the operating room for decompressive fasciotomy, debridement, drainage,
and irrigation of what cultures subsequently revealed to be a virulent
streptococcal infection. Important anatomical structures are identified in the
video as the compartments of the forearm and hand are decompressed through volar
and dorsal incisions. In the conclusion of the video, the skin is loosely
approximated over the elbow and wrist flexion creases, and a bulky gauze dressing
is applied including a plaster splint. RESULTS: The video is 6 minutes, 20-second
duration in time, and 558,180,000 bytes in size. CONCLUSIONS: This video
successfully demonstrates the anatomical approach and technique of an extensile
forearm and hand fasciotomy for compartment syndrome related to a rapidly
progressing infection.
PMID- 28697092
TI - Outpatient Anterior Cervical Discectomy and Fusion is Associated With Fewer Short
term Complications in One- and Two-level Cases: A Propensity-adjusted Analysis.
AB - STUDY DESIGN: Retrospective cohort study of prospectively collected data from the
National Surgical Quality Improvement Program (NSQIP) database. OBJECTIVE: To
determine the postoperative morbidity of one- and two-level outpatient anterior
cervical discectomy and fusion (ACDF) relative to inpatient cases, and risk
factors for postdischarge complications. SUMMARY OF BACKGROUND DATA: ACDF is
increasingly performed as an outpatient procedure, with evidence demonstrating
outpatient one-level ACDF to be associated with fewer postoperative complications
than inpatients. The postoperative morbidity and safety of outpatient two-level
ACDF as a separate cohort is not well understood. METHODS: ACDF cases from NSQIP
2011 to 2014 were identified. Differences in baseline characteristics between
inpatient and outpatient cases were determined, and propensity score adjustment
was used to account for selection bias. One- and two-level ACDF cohorts were
analyzed separately. Unadjusted and propensity-adjusted multivariable logistic
regressions were performed to determine the risk of postoperative complications
in outpatient cases relative to inpatient cases, and predictors of postdischarge
complications. RESULTS: A total of 22,006 ACDF cases were included, of which 4759
were outpatient procedures. Propensity-adjusted differences in preoperative
characteristics were all P > 0.5, indicating successful adjustment of selection
bias. Among 6890 two-level cases, of which 1429 (20.7%) were outpatient, the
overall unadjusted rate of complications was 1.47% for outpatients and 3.94% for
inpatients, P < 0.001. Propensity-adjusted multivariable regression showed a
lower rate of postoperative complications in the outpatient cohort (odds ratio
0.48, 95% confidence interval 0.30-0.75). Greater comorbidity burden as measured
by Charlson Comorbidity Index, higher American Society of Anesthesiologists
class, chronic steroid use, hypertension, and male sex were independent risk
factors for postdischarge complications. CONCLUSION: After adjusting for
selection bias and patient risk factors, outpatient two-level ACDF was not
associated with increased postoperative morbidity relative to inpatients, and may
be considered in appropriately indicated patients. LEVEL OF EVIDENCE: 3.
PMID- 28697093
TI - National Partnership for Maternal Safety: Consensus Bundle on Severe Hypertension
During Pregnancy and the Postpartum Period.
AB - Complications arising from hypertensive disorders of pregnancy are among the
leading causes of preventable severe maternal morbidity and mortality. Timely and
appropriate treatment has the potential to significantly reduce hypertension
related complications. To assist health care providers in achieving this goal,
this patient safety bundle provides guidance to coordinate and standardize the
care provided to women with severe hypertension during pregnancy and the
postpartum period. This is one of several patient safety bundles developed by
multidisciplinary work groups of the National Partnership for Maternal Safety
under the guidance of the Council on Patient Safety in Women's Health Care. These
safety bundles outline critical clinical practices that should be implemented in
every maternity care setting. Similar to other bundles that have been developed
and promoted by the Partnership, the hypertension safety bundle is organized into
four domains: Readiness, Recognition and Prevention, Response, and Reporting and
Systems Learning. Although the bundle components may be adapted to meet the
resources available in individual facilities, standardization within an
institution is strongly encouraged. This commentary provides information to
assist with bundle implementation.
PMID- 28697094
TI - Identifying and Assisting Sexually Exploited and Trafficked Patients Seeking
Women's Health Care Services.
AB - It is estimated that 21 million people are trafficked worldwide, including 11.4
million women and girls. Approximately 4.5 million are forced to do sexual labor.
The exact prevalence of human trafficking is difficult to ascertain, however,
given the limitations of data collection in an illegal industry. Obstetrician
gynecologists should not only be aware of the widespread nature of human
trafficking, but also have the tools to assess patients for trafficking and
respond to victim identifications. Patients may present with signs of physical
abuse, depression, anxiety, posttraumatic stress disorder, substance use,
sexually transmitted infections, pregnancy, and nonspecific somatic complaints.
As with intimate partner violence, clinicians should be suspicious if the patient
is accompanied by an individual who refuses to leave her side. Other potential
red flags include patients with wounds in various stages of healing, patients
appearing fearful or unable to answer specific questions, and patients who do not
have any personal identification. Health care providers should speak with the
patient privately, using professional interpreters when indicated. Although there
are no validated screening questions for the health care setting, in this
article, we provide sample questions such as, "Is anyone forcing you to do
anything physically or sexually that you do not want to do?" The physical
examination should be thorough with appropriate workup, sexually transmitted
infection prophylaxis, and emergency contraception. Physicians and patients
should be aware of their state's mandatory reporting requirements and careful
documentation is essential. Finally, to ensure a comprehensive, interdisciplinary
response to trafficked patients, practitioners should engage hospital-based and
community-based services when appropriate.
PMID- 28697095
TI - Patient Safety in Obstetrics: More Evidence, Less Emotion.
PMID- 28697096
TI - Expanded Carrier Screening: A Rational Approach to Screening for Rare Diseases.
PMID- 28697097
TI - Connect the Dots-August 2017.
PMID- 28697098
TI - Implementation of a Risk-Based Heparin Protocol for Postpartum Venous
Thromboembolism Prevention.
AB - OBJECTIVE: To evaluate the effect of a postpartum risk-based low-molecular-weight
heparin protocol for venous thromboembolism prevention. METHODS: We conducted a
retrospective cohort study of postpartum women at a safety net hospital before
(2013), during (2014), and after (2015) implementation of a risk-based enoxaparin
thromboembolism prevention protocol. The calculated sample size was based on a
primary outcome of enoxaparin administration rate. Secondary outcomes included
incidence of postpartum thromboembolism, wound complications, and 30-day
readmission rates. The prevalence of thromboembolism risk factors and protocol
adherence was evaluated in two groups of women before (May 2013) and after (May
2015) protocol implementation. Exact chi or Cochran-Armitage trend tested
differences in rates. RESULTS: Over 3 years, 9,766 deliveries were included.
Enoxaparin was administered to 0.28% (95% CI 0.14-0.55) of postpartum women in
2013 (before) compared with 33.46% (95% CI 31.89-35.07%) after protocol
implementation (P<.001). Although underpowered to detect a difference in these
outcomes, no differences were seen in rates of thromboembolism (0.16%, 0.12%,
0.15%, P=.9), wound complication (0.82%, 1.21%, 0.91%, P=.7), or emergency
department visits (8.30%, 7.96%, 8.34%, P=.9), whereas readmissions increased
(0.79%, 1.27%, 1.42%, P=.02). Prevalence of thromboembolism risk factors did not
differ between women delivered in May 2013 and May 2015. Physician adherence to
the protocol was 89.5% in May 2015. Nine women had thromboembolic events after
protocol implementation: five received appropriate treatment per protocol, but
four did not. In 2014, three of four women with a thromboembolism were
inadequately treated compared with one of five in 2015 with the addition of a
computerized order set. CONCLUSION: Implementation of a low-molecular-weight
heparin risk-based protocol for postpartum thromboembolism prevention resulted in
high physician adherence and more than 30% of postpartum women receiving
enoxaparin. Before implementing such a protocol on a wider scale, a much larger
study is needed to evaluate the effect on thromboembolic disease and wound
problems.
PMID- 28697099
TI - Intensive Prenatal Nutrition Counseling in a Community Health Setting: A
Randomized Controlled Trial.
AB - OBJECTIVE: To assess the effect of a culturally appropriate nutritional
intervention delivered to overweight and obese patients in a community health
setting on gestational weight gain and postpartum weight retention. MATERIALS AND
METHODS: We conducted a randomized controlled trial of an intensive nutrition
counseling intervention for overweight and obese women by a registered dietitian
throughout pregnancy and 6 months postpartum. The primary outcome was likelihood
of gestational weight gain within Institute of Medicine (IOM, now known as the
Health and Medicine Division of the National Academies of Sciences, Engineering,
and Medicine) guidelines. Secondary outcomes included birth weight and maternal
and neonatal complications. RESULTS: Three hundred patients were randomized. In
intent-to-treat analyses, assignment to the intervention group did not have a
significant effect on maintenance of gestational weight gain within IOM
guidelines (34.2% compared with 27.5%, odds ratio [OR] 1.4, 95% CI 0.8-2.4).
Among obese women, assignment to the intervention group was associated with fewer
large-for-gestational-age (LGA) neonates (7% compared with 17%; OR 0.3, 95% CI
0.1-0.99). Neither primary nor secondary outcomes were significantly different
among overweight women in the intervention group in intent-to-treat analyses. In
as-treated analyses, women in the intervention group had lower neonatal birth
weights (3,343 g compared with 3,500 g; difference -157.4 g, 95% CI -298.4 to
16.5) and lower likelihood of LGA (6% compared with 14%; OR 0.4, 95% CI 0.2
0.96). Among overweight women, participation in the intervention was associated
with lower gestational weight gain (26.1 pounds compared with 31.4 pounds;
difference -5.3 pounds, 95% CI -10.0 to -0.6), lower neonatal birth weights
(3,237 g compared with 3,467 g; difference -230, 95% CI -452.8 to -7.8), and
lower percent of initial body mass index at 6 months postpartum (101% compared
with 106%; difference -4.9, 95% CI -8.8 to -0.9). CONCLUSION: Our intervention
did not result in a significant improvement in our primary outcome, the
proportion of obese and overweight women who had gestational weight gain within
IOM guidelines. However, intensive prenatal nutrition counseling offered in an
urban community health setting may decrease LGA births among a group of
overweight and obese women from culturally diverse backgrounds at risk for
adverse maternal and neonatal outcomes. CLINICAL TRIAL REGISTRATION:
ClinicalTrials.gov, NCT01056406.
PMID- 28697100
TI - Venous Thromboembolism Prophylaxis During Antepartum Admissions and Postpartum
Readmissions.
AB - OBJECTIVE: To characterize the use of venous thromboembolism prophylaxis during
antepartum and postpartum hospitalizations in the United States. METHODS: A
retrospective cohort study using the Perspective database was performed to
analyze temporal trends of mechanical and pharmacologic venous thromboembolism
prophylaxis for patients hospitalized for antepartum and postpartum indications
between 2006 and 2015. Delivery hospitalizations were excluded. The association
between use of prophylaxis and medical and obstetric risk factors as well as
patient demographic and hospital characteristics was evaluated with unadjusted
and adjusted models accounting for demographic, hospital and medical, and
obstetric risk factors. RESULTS: A total of 622,740 antepartum and 105,361
postpartum readmissions were identified and included in the analysis. Between
2006 and 2015, use of venous thromboembolism prophylaxis increased from 18.5% to
38.7% for antepartum admissions (adjusted risk ratio [RR] 1.94, 95% CI 1.88-2.01)
and from 22.5% to 30.6% for postpartum readmissions (adjusted RR 1.31, 95% CI
1.21-1.43). Among women readmitted postpartum, 56.4% of prophylaxis was
pharmacologic and 43.6% was mechanical. For antepartum admissions, 87.2% of
prophylaxis was mechanical and 12.8% was pharmacologic. Significant regional and
hospital-level variation was noted with prophylaxis most common in the South. In
both unadjusted and unadjusted analyses, use of venous thromboembolism
prophylaxis was more common for women with thrombophilia, ovarian
hyperstimulation syndrome, a history of venous thromboembolism, and prolonged
hospitalization. Factors associated with decreased rates of prophylaxis included
hyperemesis and postpartum endometritis. CONCLUSION: Although antepartum and
postpartum venous thromboembolism prophylaxis is becoming increasingly common,
particularly in the setting of medical or obstetric risk factors, use of
prophylaxis varies regionally and on a hospital level. Some risk factors for
venous thromboembolism were associated with lower rates of prophylaxis. The
heterogeneity of clinical approaches to venous thromboembolism prophylaxis for
these patient populations may represent an opportunity to perform outcomes
research to further clarify best practices.
PMID- 28697101
TI - Estimating Gestational Age From Ultrasound Fetal Biometrics.
AB - OBJECTIVE: To compare the accuracy of a new formula with one developed in 1984
(and still in common use) and to develop and compare racial and ethnic-specific
and racial and ethnic-neutral formulas. METHODS: The Eunice Kennedy Shriver
National Institute of Child Health and Human Development (NICHD) Fetal Growth
Studies-Singletons was a prospective cohort study that recruited women in four
self-reported racial-ethnic groups-non-Hispanic black, Hispanic, non-Hispanic
white, and Asian-with singleton gestations from 12 U.S. centers (2009-2013).
Women with a certain last menstrual period confirmed by first-trimester
ultrasonogram had longitudinal fetal measurements by credentialed study
ultrasonographers blinded to the gestational age at their five follow-up visits.
Regression analyses were performed with linear mixed models to develop
gestational age estimating formulas. Repeated cross-validation was used for
validation. The estimation error was defined as the mean squared difference
between the estimated and observed gestational age and was used to compare the
formulas' accuracy. RESULTS: The new formula estimated the gestational age (+/-2
SD) within +/-7 days from 14 to 20 weeks of gestation, +/-10 days from 21 to 27
weeks of gestation, and +/-17 days from 28 to 40 weeks of gestation. The new
formula performed significantly better than a formula developed in 1984 with an
estimation error of 10.4 compared with 11.2 days from 21 to 27 weeks of gestation
and 17.0 compared with 19.8 days at 28-40 weeks of gestation, respectively.
Racial and ethnic-specific formulas did not outperform the racial and ethnic
neutral formula. CONCLUSION: The NICHD gestational age estimation formula is
associated with smaller errors than a well-established historical formula. Racial
and ethnic-specific formulas are not superior to a racial-ethnic-neutral one.
PMID- 28697102
TI - Secnidazole Treatment of Bacterial Vaginosis: A Randomized Controlled Trial.
AB - OBJECTIVE: To evaluate secnidazole as a single oral dose treatment for bacterial
vaginosis in a phase 2 randomized, double-blind, placebo-controlled study.
METHODS: In a phase 2, randomized, double-blind, dose-ranging, placebo-controlled
study, women with bacterial vaginosis who met all Amsel criteria (discharge; pH
4.7 or greater; 20% or greater clue cells; positive whiff test) were randomized
one to one to one at 24 U.S. centers to 1 or 2 g secnidazole compared with
placebo. The primary endpoint was clinical cure (normalization of discharge,
amine odor, and clue cells) 21-30 days after treatment. Secondary endpoints
included microbiologic cure, defined as a Nugent score of 0-3, and therapeutic
cure, defined as meeting criteria for both clinical and microbiologic cure. The
modified intent to treat was used for efficacy analyses and included all
randomized patients who met the enrollment criteria. Assuming a clinical cure
rate of 40% in the active groups and 15% in the placebo group, a sample size of
52 patients per group provided approximately 80% power to detect a significant
difference between groups (.05 level [two-sided]) using a Cochran-Mantel-Haenszel
test. RESULTS: Between May and September 2014, 215 patients were enrolled. In the
intent-to-treat population, the clinical cure rate was 65.3% for the 2-g group,
49.3% for the 1-g group, and 19.4% for the placebo group. The modified intent-to
treat population included 188 women (median age 33 years; 32% with four or more
bacterial vaginosis episodes in the previous year; 54% black) with baseline
Nugent scores 4 or greater. Clinical, microbiologic, and therapeutic cure rates
were 67.7%, 40.3%, and 40.3% for 2 g secnidazole and 51.6%, 23.4%, and 21.9% for
1 g secnidazole compared with 17.7%, 6.5%, and 6.5% for placebo, respectively
(P<.05 for secnidazole compared with placebo; all endpoints). Both doses were
well-tolerated. CONCLUSION: Oral granules containing 1 and 2 g secnidazole were
superior to placebo in bacterial vaginosis treatment (P<.001 for both groups).
These data support the development of secnidazole for bacterial vaginosis
treatment. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT02147899.
PMID- 28697103
TI - Chlorhexidine-Alcohol Compared With Povidone-Iodine for Preoperative Topical
Antisepsis for Abdominal Hysterectomy.
AB - OBJECTIVE: To compare preoperative chlorhexidine-alcohol topical antiseptic agent
with povidone-iodine in patients undergoing abdominal hysterectomy for benign
indications. METHODS: A retrospective cohort study of patients undergoing
abdominal hysterectomy from July 2012 to February 2015 in the Michigan Surgical
Quality Collaborative was performed. The primary exposure was the use of
chlorhexidine-alcohol or povidone-iodine. The primary outcome was surgical site
infection within 30 days. Multivariable logistic regression and propensity score
matching analysis were done to estimate the independent association of skin
antiseptic choice on the rate of surgical site infection. RESULTS: Of the total
4,259 abdominal hysterectomies included, chlorhexidine-alcohol was used in 70.5%
(n=3,005) and povidone-iodine in 29.5% (n=1,254) of surgeries. The overall
unadjusted rate of any surgical site infection was 2.9% (95% CI 2.5-3.5; n=124).
The unadjusted rate of surgical site infection 2.6% (95% CI 2.1-3.3; n=79) for
chlorhexidine-alcohol and 3.6% (95% CI 2.7-4.8; n=45; P=.09) for the povidone
iodine group. Using multivariate logistic regression and adjusting for
differences between populations in patient demographic factors (age and body mass
index), medical comorbidities (American Society of Anesthesiologists class and
diabetes status), perioperative variables (estimated blood loss, surgical time,
intraoperative adhesions, and antibiotic categories), and hospital
characteristics (bed size and teaching status), we estimate that patients
receiving chlorhexidine-alcohol had 44% lower odds of developing a surgical site
infection (adjusted odds ratio 0.56, 95% CI 0.37-0.85, P=.01). Propensity score
matching (one to one) yielded 808 patients in the chlorhexidine-alcohol group and
845 patients in the povidone-iodine group. In the matched groups, the rate of
surgical site infection was 1.5% (95% CI 0.8-2.6; n=12) for the chlorhexidine
alcohol group and 4.7% (95% CI 3.5-6.4; n=40) for the povidone-iodine group
(P<.001). CONCLUSION: In abdominal hysterectomy performed for benign indications,
chlorhexidine-alcohol-based skin antisepsis is associated with overall lower odds
of surgical site infection compared with povidone-iodine.
PMID- 28697104
TI - Lipschutz Ulcers: A Rare Diagnosis in Women With Vulvar Ulceration.
AB - BACKGROUND: Lipschutz ulcers are characterized by painful vulvar ulceration, most
commonly in young women. Because these lesions are so rarely seen, the diagnosis
can be challenging. CASE: An 18-year-old woman, without any prior sexual
activity, developed painful blue vulval lesions. These became necrotizing ulcers,
and she began antiviral therapy for presumptive herpes infection. Herpes
cultures, however, were negative. Serology consistent with a recent Epstein-Barr
virus infection resulted in a diagnosis of Lipschutz ulcers. CONCLUSION:
Lipschutz ulcers, associated with acute Epstein-Barr virus infection or other
viral and bacterial infections, are a type of nonsexually transmitted vulvar
ulceration. It is important to avoid selective attention to sexually transmitted
infections as the etiology to avoid unnecessary antiviral therapy and immune
suppressants. By considering other etiologies, the patient will be spared
potentially embarrassing persistent questioning about her sexual history.
PMID- 28697105
TI - Transient Fetal Tachycardia After Intravenous Diphenhydramine Administration.
AB - BACKGROUND: Fetal tachycardia is attributable to a variety of etiologies,
including an untreated maternal medical condition or an indicator of potential
fetal compromise. Maternal medication administration may also affect the fetal
heart rate. CASE: A 28-year-old nulliparous patient at 41 weeks of gestation was
treated for pruritus with intravenous diphenhydramine after epidural
administration of fentanyl. Within 14 minutes, the fetal heart rate increased
from a baseline of 155 beats per minute (bpm) to more than 200 bpm while
maintaining moderate variability. This was accompanied by an increase in uterine
contractions occurring every 1.5 minutes. The fetal tachycardia lasted 51
minutes; several hours later, a healthy neonate was delivered. CONCLUSION:
Diphenhydramine may produce transient fetal tachycardia as well as increased
maternal uterine activity.
PMID- 28697106
TI - Readmission After Gynecologic Surgery: A Comparison of Procedures for Benign and
Malignant Indications.
AB - OBJECTIVE: To compare 30-day postsurgical readmission rates and associated risk
factors for readmission among women undergoing gynecologic surgery for benign and
malignant conditions. METHODS: In a retrospective cohort study, we identified
patients after surgery for benign and malignant gynecologic conditions in the
National Surgical Quality Improvement Program database between January 1, 2011,
and December 31, 2012. Data collected included surgical factors, perioperative
characteristics, surgical complications, and 30-day readmissions. The primary
study outcome was readmission rates after gynecologic surgery for benign and
oncologic conditions. Secondary study outcomes were risk factors associated with
readmission among gynecologic surgeries performed for benign and oncologic
conditions. RESULTS: Approximately 3% (1,444/46,718) compared with 8.2%
(623/7,641) of patients who underwent gynecologic surgery for benign and
malignant indications, respectively, were readmitted (P<.01). Compared with
patients with benign surgical indications, those with uterine cancer (readmission
rate 6.6%; odds ratio [OR] 2.21, 95% CI 1.95-2.51), ovarian cancer (readmission
rate 10.9%; OR 3.82, 95% CI 3.29-4.45), and cervical cancer (readmission rate
10.1%; OR 3.51, 95% CI 2.71-4.53) were more likely to be readmitted. In
multivariable models, independent risk factors for readmission for gynecologic
cancer surgery included worse preoperative conditions (OR 1.49, 95% CI 1.17-1.90)
and major complications (OR 17.84, 95% CI 14.19-22.43). In comparison,
independent risk factors for readmission after surgery for benign indications
included comorbid conditions (OR 1.36, 95% CI 1.18-1.57), operative time (15-59
minutes: referent; 60 minutes or greater: 1.37, 95% CI 1.14-1.63) and major
complications (OR 53.91, 95% CI 46.98-61.85). CONCLUSION: Among gynecologic
surgeries, those performed for oncologic indications were associated with
readmission rates 2.8 times that of surgeries performed for benign indications.
In adjusted models, worse preoperative conditions and surgical complications
remained independent risk factors associated with the higher rate of readmission
among patients with gynecologic cancer.
PMID- 28697107
TI - Relationship Between Labor and Delivery Unit Management Practices and Maternal
Outcomes.
AB - OBJECTIVE: To define, measure, and characterize key competencies of managing
labor and delivery units in the United States and assess the associations between
unit management and maternal outcomes. METHODS: We developed and administered a
management measurement instrument using structured telephone interviews with both
the primary nurse and physician managers at 53 diverse hospitals across the
United States. A trained interviewer scored the managers' interview responses
based on management practices that ranged from most reactive (lowest scores) to
most proactive (highest scores). We established instrument validity by conducting
site visits among a subsample of 11 hospitals and established reliability using
interrater comparison. Using a factor analysis, we identified three themes of
management competencies: management of unit culture, patient flow, and nursing.
We constructed patient-level regressions to assess the independent association
between these management themes and maternal outcomes. RESULTS: Proactive
management of unit culture and nursing was associated with a significantly higher
risk of primary cesarean delivery in low-risk patients (relative risk [RR] 1.30,
95% CI 1.02-1.66 and RR 1.47, 95% CI 1.13-1.92, respectively). Proactive
management of unit culture was also associated with a significantly higher risk
of prolonged length of stay (RR 4.13, 95% CI 1.98-8.64), postpartum hemorrhage
(RR 2.57, 95% CI 1.58-4.18), and blood transfusion (RR 1.87, 95% CI 1.12-3.13).
Proactive management of patient flow and nursing was associated with a
significantly lower risk of prolonged length of stay (RR 0.23, 95% CI 0.12-0.46
and RR 0.27, 95% CI 0.11-0.62, respectively). CONCLUSION: Labor and delivery unit
management varies dramatically across and within hospitals in the United States.
Some proactive management practices may be associated with increased risk of
primary cesarean delivery and maternal morbidity. Other proactive management
practices may be associated with decreased risk of prolonged length of stay,
indicating a potential opportunity to safely improve labor and delivery unit
efficiency.
PMID- 28697108
TI - Economic Evaluation of Adjunctive Azithromycin Prophylaxis for Cesarean Delivery.
AB - OBJECTIVE: To compare the costs associated with adjunctive azithromycin compared
with standard cefazolin antibiotic prophylaxis alone for unscheduled and
scheduled cesarean deliveries. METHODS: A decision analytic model was created to
compare cefazolin alone with azithromycin plus cefazolin. Published incidences of
surgical site infection after cesarean delivery were used to estimate the
baseline incidence of surgical site infection in scheduled and unscheduled
cesarean delivery using standard antibiotic prophylaxis. The effectiveness of
adjunctive azithromycin prophylaxis was obtained from published randomized
controlled trials for unscheduled cesarean deliveries. No randomized study of its
use in scheduled procedures has been completed. Cost estimates were obtained from
published literature, hospital estimates, and the Healthcare Cost and Utilization
Project and considered costs of azithromycin and surgical site infections. A
series of sensitivity analyses were conducted by varying parameters in the model
based on observed distributions for probabilities and costs. The outcome was cost
per cesarean delivery from a health system perspective. RESULTS: For unscheduled
cesarean deliveries, cefazolin prophylaxis alone would cost $695 compared with
$335 for adjunctive azithromycin prophylaxis, resulting in a savings of $360 (95%
CI $155-451) per cesarean delivery. In scheduled cesarean deliveries, cefazolin
prophylaxis alone would cost $254 compared with $111 for adjunctive azithromycin
prophylaxis, resulting in a savings of $143 (95% CI 98-157) per cesarean
delivery, if proven effective. These findings were robust to a multitude of
inputs; as long as adjunctive azithromycin prevented as few as seven additional
surgical site infections per 1,000 unscheduled cesarean deliveries and nine
additional surgical site infections per 10,000 scheduled cesarean deliveries,
adjunctive azithromycin prophylaxis was cost-saving. CONCLUSION: Adjunctive
azithromycin prophylaxis is a cost-saving strategy in both unscheduled and
scheduled cesarean deliveries.
PMID- 28697109
TI - Pregnancy-Related Mortality in the United States, 2011-2013.
AB - OBJECTIVE: To update national population-level pregnancy-related mortality
estimates and examine characteristics and causes of pregnancy-related deaths in
the United States during 2011-2013. METHODS: We conducted an observational study
using population-based data from the Pregnancy Mortality Surveillance System to
calculate pregnancy-related mortality ratios by year, age group, and race
ethnicity groups. We explored 10 cause-of-death categories by pregnancy outcome
during 2011-2013 and compared their distribution with those in our earlier
reports since 1987. RESULTS: The 2011-2013 pregnancy-related mortality ratio was
17.0 deaths per 100,000 live births. Pregnancy-related mortality ratios increased
with maternal age, and racial-ethnic disparities persisted with non-Hispanic
black women having a 3.4 times higher mortality ratio than non-Hispanic white
women. Among causes of pregnancy-related deaths, the following groups contributed
more than 10%: cardiovascular conditions ranked first (15.5%) followed by other
medical conditions often reflecting pre-existing illnesses (14.5%), infection
(12.7%), hemorrhage (11.4%), and cardiomyopathy (11.0%). Relative to the most
recent report of Pregnancy Mortality Surveillance System data for 2006-2010, the
distribution of cause-of-death categories did not change considerably. However,
compared with serial reports before 2006-2010, the contribution of hemorrhage,
hypertensive disorders of pregnancy, and anesthesia complications declined,
whereas that of cardiovascular and other medical conditions increased (population
level percentage comparison). CONCLUSION: The pregnancy-related mortality ratio
and the distribution of the main causes of pregnancy-related mortality have been
relatively stable in recent years.
PMID- 28697110
TI - Risk of Subsequent Ovarian Cancer After Ovarian Conservation in Young Women With
Stage I Endometrioid Endometrial Cancer.
AB - OBJECTIVE: To examine the cumulative incidence of subsequent ovarian cancer among
young women with stage I endometrioid endometrial cancer who had ovarian
conservation at surgical treatment. METHODS: This retrospective study examined
the Surveillance, Epidemiology, and End Results Program to identify women aged
younger than 50 years who underwent hysterectomy with ovarian conservation for
stage I endometrioid endometrial cancer between 1983 and 2013. Time-dependent
risk of ovarian cancer diagnosed during the follow-up after endometrial cancer
diagnosis was examined. RESULTS: Among 1,322 women in the study cohort, 16 women
developed subsequent ovarian cancer with 5- and 10-year cumulative incidences of
1.0% and 1.3%, respectively. Median time to develop subsequent ovarian cancer was
2.4 years, and the majority of subsequent ovarian cancer was diagnosed within the
first 3 years from the diagnosis of endometrial cancer (68.8%). The majority of
subsequent ovarian cancer was endometrioid type (81.3%) and stage I disease
(75.0%). With a median follow-up time of 11.6 years, there were no ovarian cancer
deaths. Younger age at endometrial cancer diagnosis was significantly associated
with increased risk of subsequent ovarian cancer (10-year cumulative incidences:
age younger than 40 compared with 40-49 years, 2.6% compared with 0.4%, hazard
ratio 5.00, 95% confidence interval [CI] 1.60-15.7, P=.002). CONCLUSION: Young
women with stage I endometrioid endometrial cancer have an approximately 1% risk
of developing subsequent ovarian cancer after ovarian conservation at the time of
hysterectomy that was associated with favorable tumor factors resulting in good
ovarian cancer-specific survival. Our results endorse the importance of genetic
testing and close follow-up when counseling about this procedure, especially for
those who are younger than 40 years.
PMID- 28697111
TI - Ninety-Day Mortality as a Reporting Parameter for High-Grade Serous Ovarian
Cancer Cytoreduction Surgery.
AB - OBJECTIVE: To evaluate the utility of using 90-day as an adjunct to 30-day
mortality rates after surgical cytoreduction for serous ovarian cancer and to
compare them across hospitals of differing case volumes over time. METHODS: We
performed a retrospective cohort study using the National Cancer Database of
women undergoing cytoreductive surgery for high-grade serous carcinoma between
2004 and 2012. The primary outcome of the study was mortality rate by hospital
volume. The secondary outcome was to evaluate the performance of hospital
rankings based on 30- and 90-day mortality rates. Hospitals were categorized by
cases per year as low volume (10 or fewer), intermediate (11-20), high (21-30),
and ultra-high (31 or more). RESULTS: A total of 24,827 women from 602 hospitals
were included. Overall 30-day mortality was 2.1% (95% CI 1.95-2.3) compared with
90-day mortality of 5.1% (95% CI 4.8-5.4%, P<.001). For each hospital volume
category, the 90-day mortality was approximately double that of the 30-day
mortality. Substituting 90-day in place of 30-day mortality for hospital ranking,
57 hospitals (9.5%) changed ranks (26 worsened and 31 improved). Based on the
logistic regression model (after controlling for age, race-ethnicity, income,
Charlson comorbidity index, insurance status, hospital volume, distance from
place of residence to the hospital, receipt of neoadjuvant chemotherapy, and year
of diagnosis), care at the ultra-high-volume centers was an independent predictor
of lower odds of death at 90 days [adjusted odds ratios (OR) 0.60, 95% CI 0.38
0.96, P=.034] but not at 30 days (adjusted OR 0.64, 95% CI 0.35-1.18).
CONCLUSION: Compared with low-volume centers, ultra-high-volume centers are
associated with significantly lower 30- and 90-day risk-adjusted mortality. The
90-day mortality rate is double that of the 30-day rate and may be a better
metric for assessing the initial quality of care for patients with ovarian
cancer.
PMID- 28697112
TI - Contraception After Delivery Among Publicly Insured Women in Texas: Use Compared
With Preference.
AB - OBJECTIVE: To assess women's preferences for contraception after delivery and to
compare use with preferences. METHODS: In a prospective cohort study of women
aged 18-44 years who wanted to delay childbearing for at least 2 years, we
interviewed 1,700 participants from eight hospitals in Texas immediately
postpartum and at 3 and 6 months after delivery. At 3 months, we assessed
contraceptive preferences by asking what method women would like to be using at 6
months. We modeled preference for highly effective contraception and use given
preference according to childbearing intentions using mixed-effects logistic
regression testing for variability across hospitals and differences between those
with and without immediate postpartum long-acting reversible contraception (LARC)
provision. RESULTS: Approximately 80% completed both the 3- and 6-month
interviews (1,367/1,700). Overall, preferences exceeded use for both-LARC: 40.8%
(n=547) compared with 21.9% (n=293) and sterilization: 36.1% (n=484) compared
with 17.5% (n=235). In the mixed-effects logistic regression models, several
demographic variables were associated with a preference for LARC among women who
wanted more children, but there was no significant variability across hospitals.
For women who wanted more children and had a LARC preference, use of LARC was
higher in the hospital that offered immediate postpartum provision (P<.035) as it
was for U.S.-born women (odds ratio [OR] 2.08, 95% CI 1.17-3.69) and women with
public prenatal care providers (OR 2.04, 95% CI 1.13-3.69). In the models for
those who wanted no more children, there was no significant variability in
preferences for long-acting or permanent methods across hospitals. However, use
given preference varied across hospitals (P<.001) and was lower for black women
(OR 0.26, 95% CI 0.12-0.55) and higher for U.S.-born women (OR 2.32, 95% CI 1.36
3.96), those 30 years of age and older (OR 1.82, 95% CI 1.07-3.09), and those
with public prenatal care providers (OR 2.04, 95% CI 1.18-3.51). CONCLUSION:
Limited use of long-acting and permanent contraceptive methods after delivery is
associated with indicators of health care provider and system-level barriers.
Expansion of immediate postpartum LARC provision as well as contraceptive
coverage for undocumented women could reduce the gap between preference and use.
PMID- 28697113
TI - Paracervical Block for Laminaria Insertion Before Second-Trimester Abortion: A
Randomized Controlled Trial.
AB - OBJECTIVE: To evaluate the efficacy of a paracervical block to decrease pain
during osmotic dilator insertion before second-trimester abortion. METHODS: In
this double-blind, randomized trial, 41 women undergoing Laminaria insertion
before a second-trimester abortion received either a paracervical block with 18
mL 1% lidocaine and 2 mL sodium bicarbonate or a sham block. Women were between
14 and 23 6/7 weeks of gestation. The primary outcome was pain immediately after
insertion of Laminaria. Women assessed their pain on a 100-mm visual analog
scale. Secondary outcomes included assessment of pain at other times during the
insertion procedure and overall satisfaction with pain control. To detect a 25-mm
difference in pain immediately after Laminaria insertion, at an alpha of 0.05 and
80% power, we aimed to enroll 20 patients in each arm. RESULTS: From May 2015 to
December 2015, 20 women received a paracervical block and 21 received a sham
block. Groups were similar in demographics, including parity, history of surgical
abortion, and number of Laminaria placed. The paracervical block reduced pain
after Laminaria insertion (median scores 13 mm [interquartile range 2-39]
compared with 54 mm [interquartile range 27-61], P=.01, 95% CI -47.0 to -4.0).
Women who received a paracervical block also reported higher satisfaction with
overall pain control throughout the entire Laminaria insertion procedure (median
scores 95 mm [interquartile range 78-100] compared with 70 mm [interquartile
range 44-90], P=.05, 95% CI 0.0-37.0). CONCLUSION: Paracervical block is
effective at reducing the pain of Laminaria insertion. Additionally, a
paracervical block increases overall patient satisfaction with pain control
during Laminaria placement. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov,
NCT02454296.
PMID- 28697114
TI - All That Is Left Unsaid.
PMID- 28697115
TI - Selective Progesterone Receptor Modulators for the Treatment of Uterine
Leiomyomas.
AB - Uterine leiomyomas have drawn much attention since being described more than 200
years ago. These common benign uterine tumors often present with prolonged
menstrual bleeding, pelvic pressure, and reproductive disorders and pose a true
financial burden on health care systems all over the world. Over the past few
decades, surgical treatment of uterine leiomyomas has received most of the focus
compared with other treatment options. Choosing the appropriate surgical
technique depends on many factors such as uterine leiomyoma location, patient's
age, interest in future fertility, concomitant comorbidities, and the patient's
preference. Pharmacologic treatments such as gonadotropin-releasing hormone
agonists and antagonists have been used for the treatment of symptomatic uterine
leiomyomas with only partial success. Myriad side effects and limited clinical
results have rendered them less popular and have exposed a true need for new
effective medical treatments. Recently, treatment with selective progesterone
receptor modulators has shown promising results with shrinkage of uterine
leiomyomas and a prolonged clinical effect. Selective progesterone receptor
modulators provide hope for women with this challenging condition and are a
promising new option in the armamentarium of medical treatments for uterine
leiomyomas.
PMID- 28697116
TI - Risk Factors for Emergency Department Visits After Hysterectomy for Benign
Disease.
AB - OBJECTIVE: To identify the incidence, indications, and risk factors for emergency
department visits that do not result in readmission within 30 days of
hysterectomy for benign disease. METHODS: We conducted a secondary data analysis
of hysterectomies for benign disease using the Michigan Surgical Quality
Collaborative, a statewide group of hospitals that voluntarily reports
perioperative outcomes. Hysterectomies for benign disease were abstracted from
January 1, 2013, to July 2, 2014. We examined the incidence of emergency
department visits within 30 days after hysterectomy for benign disease and
constructed a multivariable logistic regression model to identify risk factors
for these visits. We focused on emergency department visits that did not result
in readmission because they are more likely to represent avoidable encounters.
RESULTS: Among the 10,274 women who underwent hysterectomy for benign disease
during the study period, 932 (9.1%) presented to the emergency department and
were not readmitted to the hospital. Based on a multivariable regression model,
risk factors for emergency department visits after hysterectomy for benign
disease were younger age, higher parity, Medicaid or self-pay insurance, prior
venous thromboembolism, chronic obstructive pulmonary disease, preoperative
surgical indication of chronic pelvic pain, and postoperative day 1 pain scores
greater than 4 on a 0-10 numeric rating scale. The most common primary emergency
department International Classification of Diseases, 9th Revision diagnoses were
for pain (29.5% [n=275]), gastrointestinal (12.8% [n=118]), and genitourinary
(10.7% [n=99]) complaints. CONCLUSION: Approximately 1 in 11 women present to the
emergency department, but do not result in readmission within 30 days of
hysterectomy for benign disease. Emergency department visits might be avoided
with expanded perioperative education and improved communication pathways for
high-risk patients.
PMID- 28697117
TI - Video Colposcopy for Reducing Patient Anxiety During Colposcopy: A Randomized
Controlled Trial.
AB - OBJECTIVE: To test whether video colposcopy reduces anxiety among patients
undergoing colposcopy. METHODS: In a prospective, randomized multicenter trial,
we compared video colposcopy and no video colposcopy in a one-to-one ratio.
Situation-specific anxiety was measured before (S1) and after (S2) colposcopy
using the State-Trait Anxiety Inventory. The primary endpoint was the reduction
of the situation-specific anxiety scores (DeltaS=S2-S1). Secondary endpoints were
pain during and 10 minutes after colposcopy, general unpleasantness, anxiety
during colposcopy, satisfaction with the information about the procedure, and
overall satisfaction (11-item visual analog scales). Analysis was by intention to
treat. A sample size of 104 per group (n=208) was planned to achieve 80% power to
detect a difference of 4.8 with a SD of 12.3 in the primary outcome. RESULTS:
Between August 2016 and March 2017, 225 women were randomized. The mean DeltaS
was -10.3+/-11.3 SD in 111 women in the video colposcopy group and -10.3+/-11.0
SD in 105 women without video colposcopy (P=.50). The secondary endpoints pain
during examination (median 2 [interquartile range 1-3] compared with 2 [1-4];
P=.91), pain 10 minutes after examination (1 [0-3] compared with 1 [0-2.5];
P=.24), general unpleasantness (3 [1-5] compared with 3 [1-5]; P=.90), anxiety
during examination (3 [1-5] compared with 3 [1-5]; P=.61), satisfaction with the
information about the procedure (10 [9-10] compared with 10 [9-10]; P=.88), and
overall satisfaction (10 [9-10] compared with 10 [9-10]; P=.54) were also not
different between the two study groups. In a multivariate linear regression
analysis, study center (P=.028), body mass index (P=.033), and smoking status
(P=.025) independently affected the reduction of anxiety. CONCLUSION: Video
colposcopy does not reduce anxiety in women undergoing colposcopy. CLINICAL TRIAL
REGISTRATION: ClinicalTrials.gov, NCT02697175.
PMID- 28697118
TI - Finding Middle Ground in Constructing a Clinically Useful Expanded Carrier
Screening Panel.
AB - Expanded carrier screening for autosomal-recessive conditions effectively
identifies more carrier couples than traditional guideline-based carrier
screening. However, clinically available expanded carrier screening panels
include numerous conditions, some of which have questionable clinical utility as
a result of very low carrier frequency, low or unknown testing sensitivity, and
mild or incompletely penetrant phenotypes. Using the 2013 American College of
Medical Genetics and Genomics Position Statement on Prenatal and Preconception
Expanded Carrier Screening and the 2017 American College of Obstetricians and
Gynecologists' Committee Opinion on Carrier Screening in the Age of Genomic
Medicine as guidance, we propose specific criteria for the development of
expanded carrier screening panels that will maximize clinical utility and
minimize patient stress, unnecessary cost of follow-up testing, and clinician
time spent facilitating and performing follow-up counseling and testing. We
identified 96 conditions that meet our proposed criteria, far more than current
guidelines recommend. On the other hand, a considerable percentage (73%) of
conditions on current expanded carrier screen panels does not meet our proposed
criteria. The purpose of this commentary is to acknowledge the benefits of
expanded panels, but to also recognize that in their current state, we are
putting patients at risk for undue stress and spending excessive time and money
on follow-up testing for remarkably rare or mild conditions and conditions with
low screening performance. We encourage laboratories and clinicians to work
together to create the most clinically useful screening panels for patients
desiring reproductive risk information.
PMID- 28697119
TI - When Guild Interests and Professional Obligations Collide.
AB - Physicians who work in medical organizations are called on to fulfill two roles:
guild members who work to advance physician interests (eg, lobbying for tort
reform) and professional society members who work to advance patient interests
(eg, developing clinical guidelines). Most often, physicians' self-interest and
their interest in patient well-being align. When they do not, members of a guild
or profession may justify the prioritization of self-interest with a form of
motivated reasoning (a process wherein physicians weigh data differently
depending on whether it supports their a priori beliefs). This allows physicians
to frame self-interest as being in the best interests of their patients (eg, tort
reform makes malpractice insurance affordable and allows physicians to continue
to serve their patients). When interests conflict, physicians must be cognizant
of the forces at play, that is, self-interest or in-group interest on the one
hand and obligations to patients on the other. This entails recognition and
negation of motivated reasoning. Often the most difficult calculus is evaluating
proposed actions that would disadvantage physicians but advantage patients. In
such cases, the health care provider must be aware not only of the temptation to
oppose the action for financial reasons, but also the equally natural temptation
to frame the proposal as a threat to patient well-being. Ultimately recognizing
that a central tenet of professionalism is the primacy of patient welfare should
help physicians both to maintain their fidelity to patient good and to uphold
their reputation for altruism.
PMID- 28697120
TI - Association of Parasite Load Levels in Amniotic Fluid With Clinical Outcome in
Congenital Toxoplasmosis.
AB - OBJECTIVE: To correlate neonatal and infant clinical outcome with parasite load
in amniotic fluid (AF). METHODS: We conducted a retrospective cohort study of 122
children whose mothers had toxoplasmosis during pregnancy. The children were
monitored from birth to 12 months old. Stored AF samples were obtained at
maternal diagnosis and tested by quantitative polymerase chain reaction.
Gestational age at maternal infection, quantitative polymerase chain reaction
results, neonatal anti-Toxoplasma gondii immunoglobulin (Ig) M, and clinical
outcome at 12 months were correlated. RESULTS: Maternal infection occurred in 18
of 122 (14.7%) and 104 of 122 (85.2%) women in the first and second trimesters,
respectively. At birth, IgM was present in 107 of 122 (87.7%) neonates and 36
(29.5%) were symptomatic. Of these, half occurred in the first and the other half
in the second trimester and 6 of 36 had severe infections (16.7% of symptomatic,
4.9% of total), all infected in the first trimester. Parasite load levels were
highly variable (median 35 parasites/mL, range 2-30,473). Logistic regression
correlated symptomatic infection with gestational age (odds ratio [OR] 0.47, CI
0.31-0.73) and parasite load (OR 2.04, CI 1.23-3.37), but not with positive IgM
(OR 6.81, CI 0.86-53.9). Negative correlations were found between gestational age
and parasite load (rs -0.780, CI -0.843 to -0.696), gestational age and symptoms
(rs -0.664, CI -0.755 to -0.547), but not gestational age and IgM (rs -0.136, CI
0.311 to 0.048). Parasite load levels distributed by percentile showed that all
symptomatic patients appeared from the 75th percentile and all severe infections
from the 95th percentile. Load rankings showed doubled the OR for each 20
parasite/mL increment. Parasite load was associated with symptomatic infections
(area under the curve 0.959, CI 0.908-0.987) as well as gestational age (area
under the curve 0.918, CI 0.855-0.960) and both parameters combined (area under
the curve 0.969, CI 0.920-0.992). CONCLUSION: Parasite load in AF is associated
with the clinical outcome in congenital toxoplasmosis, irrespective of
gestational age at maternal infection.
PMID- 28697121
TI - What Is New in Obstetric Imaging?: Best Articles From the Past Year.
AB - This month we focus on current research in obstetric imaging. Dr. Dashe discusses
five recent publications, which are concluded with a "bottom line" that is a take
home message. A complete reference for each can be found in on this page along
with direct links to abstracts.
PMID- 28697122
TI - The Emerging Role of Endoscopists in Treating Unresectable Pancreatic Cancer.
AB - Pancreatic adenocarcinoma is the eighth leading cause of cancer deaths worldwide
in men and ninth leading cause in women. Surgical resection offers the only
chance of potential cure; however, only 9.4% of patients present at the
localized, resectable stage, whereas the rest present at the locally advanced or
metastatic, unresectable stages. Because of the guarded outcomes following
systemic chemoradiation and the associated systemic toxicities, locoregional
therapies have recently gained popularity. Various endoscopic techniques
(endoscopic ultrasound [EUS]-guided ablative therapies, fine-needle instillation
of antitumor agents, stereotactic body radiation therapy with EUS-guided fiducial
marker placement, and EUS-guided brachytherapy) have been explored over the past
several years. Endoscopic therapy plays a role in the treatment of unresectable
pancreatic adenocarcinoma. Its minimal invasiveness and increased precision of
delivering oncologic treatments under EUS guidance render it as a favorable
option for patients who do not benefit from surgical resection. New endoscopic
therapies are currently under investigation, and the emerging role of the
endoscopist in the treatment of unresectable pancreatic cancer continues to grow.
PMID- 28697123
TI - Describing Peripancreatic Collections According to the Revised Atlanta
Classification of Acute Pancreatitis: An International Interobserver Agreement
Study.
AB - OBJECTIVES: Severe acute pancreatitis is associated with peripancreatic
morphologic changes as seen on imaging. Uniform communication regarding these
morphologic findings is crucial for accurate diagnosis and treatment. For the
original 1992 Atlanta classification, interobserver agreement is poor. We
hypothesized that for the revised Atlanta classification, interobserver agreement
will be better. METHODS: An international, interobserver agreement study was
performed among expert and nonexpert radiologists (n = 14), surgeons (n = 15),
and gastroenterologists (n = 8). Representative computed tomographies of all
stages of acute pancreatitis were selected from 55 patients and were assessed
according to the revised Atlanta classification. The interobserver agreement was
calculated among all reviewers and subgroups, that is, expert and nonexpert
reviewers; interobserver agreement was defined as poor (<=0.20), fair (0.21
0.40), moderate (0.41-0.60), good (0.61-0.80), or very good (0.81-1.00). RESULTS:
Interobserver agreement among all reviewers was good (0.75 [standard deviation,
0.21]) for describing the type of acute pancreatitis and good (0.62 [standard
deviation, 0.19]) for the type of peripancreatic collection. Expert radiologists
showed the best and nonexpert clinicians the lowest interobserver agreement.
CONCLUSIONS: Interobserver agreement was good for the revised Atlanta
classification, supporting the importance for widespread adaption of this revised
classification for clinical and research communications.
PMID- 28697124
TI - Effect of Intravenous Fluids and Analgesia on Dysmotility in Patients With Acute
Pancreatitis: A Prospective Cohort Study.
AB - OBJECTIVES: Analgesia and intravenous fluid resuscitation are cornerstones of
initial patient management in acute pancreatitis (AP). The aim was to investigate
the effect of intravenous fluids and analgesia on gastrointestinal motility in
the early course of AP. METHODS: Gastrointestinal dysmotility was assessed using
the Gastroparesis Cardinal Symptom Index (GCSI). One-way analysis of variance and
analysis of covariance were conducted, adjusting for age, sex, body mass index,
severity of AP, preexisting diabetes mellitus, and time from first symptom onset
to hospital admission. RESULTS: A total of 108 patients with AP were
prospectively enrolled. Opioid analgesia, when compared with nonopioid analgesia,
was significantly associated with increase in total GCSI score in both unadjusted
and adjusted analyses. There was no significant difference between aggressive and
nonaggressive fluid resuscitation in both unadjusted and adjusted analyses. A
combination of opioids and any intravenous fluids was associated with a
significantly increased total GCSI score compared with opioids and no intravenous
fluids in both unadjusted and adjusted analyses. Duration of symptoms was the
confounder that significantly affected 6 of 9 studied associations. CONCLUSIONS:
Intravenous fluids and analgesia significantly affect motility independent of
severity and other covariates. Guidelines on prudent use of opioids and fluids in
AP need to be developed, particularly taking into account duration of symptoms
from onset to hospitalization.
PMID- 28697125
TI - The Prognosis of Severe Acute Pancreatitis Varies According to the Segment
Presenting With Low Enhanced Pancreatic Parenchyma on Early Contrast-Enhanced
Computed Tomography: A Multicenter Cohort Study.
AB - OBJECTIVE: The aim of this study was to investigate the outcomes of severe acute
pancreatitis (SAP) according to the segment presenting with low enhanced
pancreatic parenchyma (LEPP) on early contrast-enhanced computed tomography.
METHODS: This was a post hoc analysis of a multicenter, retrospective study
conducted at 44 institutions in Japan. Patients diagnosed as having SAP according
to the Japanese Severity Score between January 2009 and December 2013 were
included. We compared the effect of LEPP in each segment on mortality. RESULTS: A
total of 1097 patients were assessed. The numbers of patients with LEPP in the
pancreatic head (Ph), body (Pb), or tail (Pt) were 272, 273, and 204 (with some
overlaps), respectively. In multivariate analysis, LEPP in Ph and Pt was
significantly related to mortality (odds ratio [OR], 1.94; 95% confidence
interval [CI], 1.11-3.40 [P < 0.05], for LEPP in Ph; OR, 2.44; 95% CI, 1.27-4.67
[P < 0.05], for LEPP in Pt), but LEPP in Pb was unrelated to mortality (OR, 0.70;
95% CI, 0.35-1.37; P = 0.30). CONCLUSIONS: Presence of LEPP in Ph and Pt on early
contrast-enhanced computed tomography was independently associated with increased
mortality in SAP. These patients require close observation to ensure timely and
adequate intervention.
PMID- 28697126
TI - Effect of Serum Triglycerides on Clinical Outcomes in Acute Pancreatitis:
Findings From a Regional Integrated Health Care System.
AB - OBJECTIVES: The aim of this study was to evaluate the effect of serum
triglycerides on the development of multiple or persistent organ failure in
patients with acute pancreatitis. METHODS: A retrospective cohort study was
conducted among patients hospitalized for acute pancreatitis between 2006 and
2013. Triglyceride levels measured before and within 72 hours of admission were
compared. In addition, the effect of triglyceride levels on the development of
multiple or persistent organ failure during hospitalization for acute
pancreatitis was assessed. RESULTS: Among 2519 patients, 267 patients (10.6%)
developed organ failure, of which 75 patients developed multiple system organ
failure and 82 patients developed persistent organ failure. Triglyceride levels
in patients who developed organ failure were initially much higher than in
patients who did not develop organ failure, but by 72 hours into admission,
approached levels of patients who did not develop organ failure. Approximately 8%
of patients had triglyceride levels greater than 500 mg/dL, the majority of which
had similarly high levels before admission. CONCLUSIONS: Increased triglyceride
levels were associated with the development of multiple or persistent organ
failure among patients hospitalized with acute pancreatitis. Patients with high
triglyceride levels at the time of admission were likely to have high
triglyceride levels before admission.
PMID- 28697127
TI - Celecoxib Oral Administration for Prevention of Post-Endoscopic Retrograde
Cholangiopancreatography Pancreatitis: A Randomized Prospective Trial.
AB - OBJECTIVES: Rectal nonsteroidal anti-inflammatory drugs have reported promising
prophylactic activity in post-endoscopic retrograde cholangiopancreatography
(ERCP) pancreatitis (PEP). Conversely, cyclooxygenase-2 enzyme has been suggested
to contribute to experimental acute pancreatitis. The aim of this study was to
evaluate the efficacy of oral administration of celecoxib, a cyclooxygenase-2
inhibitor, for the prevention of PEP. METHODS: We performed a prospective
randomized controlled study. Patients who were scheduled to undergo ERCP were
randomized to receive either oral 400-mg celecoxib tablets 1 hour before ERCP and
saline infusion (celecoxib group) or saline infusion only (control group). The
primary outcome measure was the frequency of PEP. RESULTS: A total of 170
patients were randomized; 85 patients each in the celecoxib group and control
group were analyzed. After the procedure, 23 patients (13.5%) developed PEP.
There was no difference in the frequency of PEP between the 2 groups (control
group vs celecoxib group, 15.3% (13/85) vs 11.7% (10/85); P = 0.65). The severity
of PEP, asymptomatic hyperamylasemia, and post-ERCP pain were not significantly
different between the 2 groups. There were no adverse events related to celecoxib
treatment. CONCLUSIONS: Oral administration of celecoxib had no beneficial
preventive effect on PEP.
PMID- 28697128
TI - The Impact of Risk Factors of Chronic Pancreatitis on Secretin Pancreatic
Function Testing: Results of a 20-Year Study.
AB - OBJECTIVES: The aim of this study was to determine the effect of established risk
factors on the outcome of secretin pancreatic function testing (sPFT) in patients
undergoing work-up for suspected chronic pancreatitis. METHODS: We completed a
retrospective review of patients who underwent sPFT for suspected chronic
pancreatitis over 20 years. We compared peak bicarbonate concentrations between
groups and completed univariate and multivariate analyses to determine
associations between risk factors and positive sPFT results (peak bicarbonate <80
mEq/L). RESULTS: Forty-three of 162 patients had positive sPFT results. There
were significant differences in peak bicarbonate concentrations in patients with
and without recurrent acute pancreatitis (RAP) and with local complications from
acute pancreatitis (AP) (P <= 0.05). The bicarbonate concentration in patients
with and without other risk factors such as tobacco use, alcohol use, and family
history of pancreatitis was not significantly different. Female sex, a history of
AP, and a history of RAP were associated with positive sPFT results on univariate
analysis (P <= 0.05). On multivariate analysis, sex and RAP remained significant.
CONCLUSIONS: Our study demonstrates that female sex, history of AP and RAP, and
AP with local complications are associated with positive sPFT results or lower
peak bicarbonate concentration. However, other risk factors do not impact the
results of sPFT.
PMID- 28697129
TI - Treatment Patterns and Burden of Illness in Patients Initiating Targeted Therapy
or Chemotherapy for Pancreatic Neuroendocrine Tumors.
AB - OBJECTIVE: The aim of this study was to characterize treatment patterns and
burden of pancreatic neuroendocrine tumors (PNET). METHODS: Using 2 claims
databases, we identified patients with PNET initiating targeted therapy
(everolimus, sunitinib) or chemotherapy from 2009 to 2012. The first
targeted/cytotoxic therapy was considered index treatment. Treatment patterns
were graphically evaluated from index treatment initiation until enrollment or
study end, whichever occurred first. Disease burden was examined by index group
for first follow-up year. RESULTS: In treatment pattern analyses (582 newly
treated patients with PNET), 72.2% received chemotherapy index treatment, 16.2%
everolimus, and 11.7% received sunitinib. Median index treatment duration was
242, 146, and 126 days for everolimus, sunitinib, and cytotoxics (P < 0.01).
Sunitinib initiators switched most often followed by everolimus and cytotoxic
initiators. In disease burden analyses, 338 patients met inclusion criteria, with
mean age of 54.5 (standard deviation, 9.9) years, 45.6% were female, and there
were no significant between-group differences. Targeted therapy initiators had
more prior somatostatin analog use versus cytotoxics (53.4% vs 25.1%, P < 0.001);
72.5% had comorbidities after treatment initiation; 42.9% had 1 or more inpatient
hospitalization; and 47.9% had 1 or more emergency department visit. CONCLUSIONS:
Pancreatic neuroendocrine tumor treatment patterns varied; cytotoxics were more
often used as early therapy than targeted agents, but for less time. Patients had
high health care utilization, irrespective of treatment, potentially from
burdensome symptoms and comorbidities.
PMID- 28697130
TI - Regional Metastatic Behavior of Nonfunctional Pancreatic Neuroendocrine Tumors:
Impact of Lymph Node Positivity on Survival.
AB - OBJECTIVES: Literature addressing the significance of lymph node positivity in
the management of nonfunctional pancreatic neuroendocrine tumors (PNETs) is
conflicting. METHODS: The National Cancer Data Base was queried for patients who
underwent surgical resection of nonfunctional PNETs between 1998 and 2011.
Clinical data and overall survival were analyzed using chi and Cox proportional
hazards regression. Multiple imputation was used as a comparative analysis
because of the high number of patients missing data on tumor grade. RESULTS: Two
thousand seven hundred thirty-five patients were identified. The overall
incidence of lymph node metastasis was 51%. In the subset of patients with grade
1 tumors less than 1 cm, 24% had positive lymph nodes. Overall median survival
for patients with negative lymph nodes was 11 years compared with 8 years for
lymph node-positive patients (P < 0.001). On multivariate survival analysis,
tumor grade, distant metastases, regional lymph node involvement, positive
surgical margins, male sex, and older age were predictive of decreased overall
survival. CONCLUSIONS: Lymph node positivity was associated with decreased
overall survival. The incidence of lymph node involvement in resected low-grade
tumors less than 1 cm is higher than previously reported. Patients selected for
resection of PNETs should be offered lymphadenectomy for staging.
PMID- 28697131
TI - Patterns of Care for Locally Advanced Pancreatic Adenocarcinoma Using the
National Cancer Database.
AB - OBJECTIVES: The role of radiotherapy (RT) in locally advanced pancreatic cancer
(LAPC) is uncertain. This study examines patterns of care and survival outcomes
of LAPC undergoing chemotherapy alone versus chemotherapy plus RT (C + RT).
METHODS: The National Cancer Database was queried for nonmetastatic LAPC patients
who received chemotherapy alone or C + RT. RESULTS: Of the 13,695 patients
included, 5306 underwent chemotherapy alone and 4971, C + RT. Use of C + RT
declined from 2003 to 2011 (73%-53%), whereas chemotherapy alone increased. Of
those receiving RT, rates of intensity-modulated radiotherapy (IMRT) increased
(27%-72%), whereas 3-dimensional (3D) RT decreased (73%-28%). Unadjusted 1-year
overall survival (OS) was longer for versus chemotherapy (45.6% vs 38.7%), as was
2-year OS (12.9% vs 11.9%) (hazard ratio, 0.88; 0.85-0.91; P < 0.001). Under
multivariate analysis, C + RT was associated with improved OS (hazard ratio,
0.84; 0.81-0.87; P < 0.001). On subgroup analysis comparing C + IMRT, C + 3D RT,
and chemotherapy alone, 1-year OS was 49.1%, 45.1%, and 38.7%, and 2-year OS was
13.1%, 11.6%, and 11.9% accordingly. CONCLUSIONS: Utilization of RT in LAPC is
decreasing, whereas chemotherapy alone is increasing. Of patients undergoing RT,
rates of IMRT are increasing. Whereas C + IMRT appeared to be associated with
improved OS compared with chemotherapy alone, 3D RT was not.
PMID- 28697132
TI - Overexpression of Yes Associated Protein 1, an Independent Prognostic Marker in
Patients With Pancreatic Ductal Adenocarcinoma, Correlated With Liver Metastasis
and Poor Prognosis.
AB - OBJECTIVES: Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer.
Overexpression of Yes associated protein 1 (YAP1), a downstream target of Hippo
pathway, implicated in regulation of cell growth and apoptosis, has been reported
in several human tumor types. The objective of this study was to investigate YAP1
expression in patients with PDAC and its prognostic values. METHODS: We evaluated
YAP1 expression in 64 PDAC and 15 chronic pancreatitis (CP) cases and its related
pancreatic intraepithelial neoplasia (PanIN) lesions and in 5 control subjects.
Yes associated protein 1 expression was determined by immunohistochemistry.
Association of YAP1 with clinicopathologic features in PDAC, disease-free
survival, and overall survival was analyzed. RESULTS: We found a higher positive
rate of nuclear expression of YAP1 in PDAC than in CP (P = 0.000) and lower
expression of YAP1 in PanIN lesions in CP in contrast with expression in PanIN
lesions in PDAC. Nuclear overexpression of YAP1 in PDAC is associated with
hepatic metastasis (P = 0.0280) and is a prognostic factor (P = 0.0320), as well
as surgical margin involvement (P = 0.0013) and tumoral stage (P = 0.0109).
CONCLUSIONS: Overexpression of YAP1 may occur as a part of tumorigenesis of PDAC.
Yes associated protein 1 is an independent prognostic marker for overall survival
of PDAC and associated with liver metastasis, being a potential therapeutic
target.
PMID- 28697133
TI - Pancreatic Duct in Autoimmune Pancreatitis: Intraindividual Comparison of
Magnetic Resonance Pancreatography at 1.5 T and 3.0 T.
AB - OBJECTIVE: The aim of this study was to intraindividually compare magnetic
resonance pancreatography (MRP) image quality at 1.5 T and 3.0 T when
demonstrating main pancreatic duct (MPD) abnormalities in patients with
autoimmune pancreatitis (AIP). METHODS: Thirty prospectively enrolled patients
with AIP underwent MRP at both 1.5 T and 3.0 T followed by endoscopic retrograde
pancreatography before treatment. Two readers independently analyzed the MRP
images and graded the visualization of MPD strictures and full-length MPD, using
endoscopic retrograde pancreatography as the reference standard, as well as
overall image artifacts on a 4-point scale. The contrast between the MPD and
periductal area was calculated using a region-of-interest measurement. RESULTS:
Visualization scores of MPD strictures and full-length MPD, and summed scores of
each qualitative analysis, were significantly greater at 3.0-T MRP than at 1.5-T
MRP for both readers (P <= 0.02). There were less image artifacts at 3.0 T
compared with 1.5 T (P <= 0.052). The contrast between the MPD and periductal
area was significantly greater at 3.0-T MRP than at 1.5-T MRP (P < 0.001).
CONCLUSIONS: The MRP at 3.0 T was superior to 1.5-T MRP for demonstrating MPD
abnormalities in AIP, with better image contrast and fewer image artifacts.
Consequently, 3.0-T MRP may be useful for the diagnosis and management of
patients with AIP.
PMID- 28697134
TI - Surveillance and Outcomes of Nonresected Presumed Branch-Duct Intraductal
Papillary Mucinous Neoplasms: A Meta-analysis.
AB - OBJECTIVES: Guidelines regarding the surveillance of intraductal papillary
mucinous neoplasms (IPMNs) are controversial because of uncertain risk of
malignancy, agnosticism regarding the use of endoscopic ultrasound, and their
recommendation to stop surveillance after 5 years. We present a systematic review
and meta-analysis of the risk of malignancy and other end points and estimate the
value of endoscopic ultrasound for surveillance. METHODS: We systematically
searched MEDLINE for studies with a cohort of patients with presumed branch-duct
IPMN who initially were managed nonsurgically. Data regarding study
characteristics, surveillance, and outcomes were extracted. Incidence rates of
morphologic progression, malignancy, surgery, and death were calculated with a
random effects model. RESULTS: Twenty-four studies with 3440 patients and 13,097
patient-years of follow-up were included. Rates of morphologic progression,
surgery, malignancy, and death were 0.0379, 0.0250, 0.0098, and 0.0043 per
patient-year, respectively. Endoscopic ultrasound was not associated with
significantly different rates of these outcomes. CONCLUSIONS: The risk of
malignancy calculated in this study was low and in line with recent systematic
reviews. Endoscopic ultrasound does not have marginal use in surveillance. Given
the limitations of a systematic review of nonrandomized studies, further studies
are needed to determine the optimal surveillance of branch-duct IPMNs.
PMID- 28697135
TI - Validation of the 2012 Fukuoka Consensus Guideline for Intraductal Papillary
Mucinous Neoplasm of the Pancreas From a Single Institution Experience.
AB - OBJECTIVES: The 2012 Fukuoka consensus guideline has stratified the risks of
malignant intraductal papillary mucinous neoplasm (IPMN) of the pancreas into
"high-risk stigmata" (HRS) and "worrisome feature" (WF). This study aimed to
evaluate its clinical validity based on a single institution experience. METHODS:
Eighty-nine patients who underwent surgical resection with pathological diagnosis
of IPMN were retrospectively studied. RESULTS: High-risk stigmata was
significantly correlated with the prevalence of malignant IPMN as compared with
WF. The positive predictive values of HRS and WF were 66.7% and 35.7% for branch
duct IPMN and 80% and 38.1% for main duct IPMN, respectively. Univariate analysis
indicated that all the factors in HRS and WF had statistical significance.
Whereas multivariate analysis revealed only enhanced solid component (odds ratio
[OR], 50.01; P = 0.008), presence of mural nodule (OR, 73.83; P < 0.001) and
lymphadenopathy (OR, 20.85; P = 0.03) were independent predictors. Scoring HRS
and WF by different numbers of positive factors resulted in improved predictive
value. The area under the curve of HRS score was significantly lower than that of
WF or HRS + WF score (0.680 vs 0.900 or 0.902, respectively; P < 0.001).
CONCLUSIONS: As supplementary to the 2012 Fukuoka guideline, we suggest that
calculating scores of WF and HRS may have superior diagnostic accuracy in
predicting malignant IPMN.
PMID- 28697136
TI - Circulating Epithelial Cells in Intraductal Papillary Mucinous Neoplasms and
Cystic Pancreatic Lesions.
AB - OBJECTIVES: Circulating epithelial cells (CECs) are identified in the blood of
patients with intraductal papillary mucinous neoplasms (IPMNs) despite the
absence of malignancy. We assessed the blood of patients undergoing resection for
IPMN or other benign pancreatic lesions for CECs. METHODS: Peripheral blood was
collected from 26 patients prior to pancreatic resection and filtered by the ISET
(Isolation by Size of Epithelial Tumor Cells) method. Circulating epithelial
cells were identified with antibodies to cytokeratin and Pdx1 (pancreas and
duodenal homeobox protein 1), a pancreas marker. RESULTS: Nineteen patients
underwent resection of an IPMN without associated malignancy. Eleven patients
(58%) had cytokeratin-positive CECs. Circulating epithelial cells were
significantly more likely to be found in patients with IPMNs with high-grade
dysplasia (P = 0.04). In addition, 10 of the 11 patients with cytokeratin
positive CECs also had separate populations of cytokeratin-positive, Pdx1
positive CECs, suggesting a pancreatic source. Dual-staining CECs were more
frequently found in patients with high-grade dysplasia (P = 0.04). Patients with
IPMNs were significantly more likely to have pan-cytokeratin CECs in the blood
compared with those without IPMNs (P = 0.01). CONCLUSIONS: Circulating epithelial
cells staining with potential pancreas-specific markers have been found in
patients with IPMNs, even without malignancy. Circulating epithelial cells may
help to differentiate patients with high-grade IPMN from lower grades of
dysplasia and other pancreatic cysts.
PMID- 28697137
TI - Clinical Profile of Pancreatic Cystic Lesions in von Hippel-Lindau Disease: A
Series of 48 Patients Seen at a Tertiary Institution.
AB - OBJECTIVES: Little is known about the association between pancreatic cystic
lesions (PCLs) with von Hippel-Lindau disease (VHLD). In this study, we describe
the clinical presentation, type of PCLs, and risk for malignancy in PCLs in VHLD.
METHODS: Patients given a diagnosis of both VHLD and PCLs were identified from
electronic medical records at Mayo Clinic, Rochester, MN, from January 1, 2000,
to January 1, 2016. Various demographic, clinical, and radiologic variables were
recorded. RESULTS: Forty-eight patients were identified with PCLs and VHLD. Most
were female (73%), and mean (standard deviation) age was 35.9 (14.2) years. Most
(92%) were asymptomatic. PCLs included simple cysts (n = 34, 69%), serous
cystadenoma (n = 14, 29%), branch duct intraductal papillary neoplasm (n = 5,
10%), and cystic neuroendocrine tumors (n = 2, 4%). Eight (19%) had mixed PCLs.
Cyst aspiration was performed in 8 (53%) patients who underwent EUS, and all were
negative for malignancy. At a median follow-up of 84 months, no PCL-associated
cancers were seen. CONCLUSIONS: Simple cyst is the most common type of PCL found
in VHL disease; however, other PCLs were also seen with no malignancy potential.
Branch duct intraductal papillary mucinous neoplasms were present in 10%, and
this association was not hitherto reported.
PMID- 28697138
TI - Proceedings of the 1st International Conference for Cancer Metabolism and
Therapy, October 14-17, 2016, Dalian, China.
PMID- 28697139
TI - A Rare Case of Pancreatic Tuberculosis.
AB - Tuberculosis remains a major public health concern, although it has reportedly
shown a decline in prevalence both in the United States and abroad in recent
years. The focus on diagnosing and treating tuberculosis is on pulmonary
tuberculosis. Meanwhile, pancreatic tuberculosis remains exceedingly rare,
accounting for less than 5% (Gastroenterol Rep (Oxf), 2014;2:154-157) of all
tuberculosis cases in the developing world. A literature review shows that the
head is primarily affected in pancreatic tuberculosis (Gastroenterol Rep (Oxf),
2014;2:154-157).
PMID- 28697140
TI - Response to Somatostatin Analog Therapy in a Patient With von Hippel-Lindau
Disease and Multiple Pancreatic Neuroendocrine Tumors.
PMID- 28697141
TI - Periprocedural Intravenous Fluid Administration for the Prevention of Post
Endoscopic Retrograde Cholangiopancreatography Pancreatitis.
PMID- 28697142
TI - Plasmapheresis for Hypertriglyceridemia-Induced Acute Pancreatitis in a Child: A
Case Report and Brief Review of the Literature.
PMID- 28697143
TI - Pancreatic Cystic Lesions: A Challenging Entity in Children.
PMID- 28697144
TI - Assessment of the Utility of Laparoscopy and Peritoneal Cytology in the Staging
of Pancreatic Cancer.
PMID- 28697145
TI - Carbon Dioxide Insufflation During Endoscopic Pancreatic Function Tests Does Not
Alter Duodenal Aspirate Bicarbonate Concentrations.
PMID- 28697146
TI - Gastric Reflux Into the Gallbladder After EUS-guided Stenting-Letter to the
Editor Regarding "EUS-guided Versus Percutaneous Gallbladder Drainage: Isn't It
Time to Convert?"
PMID- 28697147
TI - Reply to Potential Pitfalls When Assessing the Impact of Cytomegalovirus in
Inflammatory Bowel Disease.
PMID- 28697148
TI - Consideration of Clinical Context and Alternative Therapies in Aggressive
Resuscitation for Prevention of Post-ERCP Pancreatitis.
PMID- 28697149
TI - The Influence of Statins on Risk and Patient Survival in Colorectal Cancer.
PMID- 28697150
TI - Endoscopic Retrograde Cholangiopancreatography (ERCP) and Acute Cholangitis: The
Sooner, the Better.
PMID- 28697151
TI - EUS-guided Gastrojejunostomy Versus Laparoscopic Gastrojejunostomy: An
International Collaborative Study.
AB - INTRODUCTION: Endoscopic ultrasound-guided gastrojejunostomy (EUS-GJ) with
placement of a lumen-apposing metal stent is a minimally invasive and efficacious
procedure for gastric outlet obstruction (GOO) patients not amenable to surgery.
Laparoscopic gastrojejunostomy (Lap-GJ) has traditionally been the standard of
care. No direct comparison between EUS-GJ and Lap-GJ has been described. Our aim
was to compare the clinical outcomes, success rate, and adverse events (AE) of
EUS-GJ with Lap-GJ. METHODS: Patients with GOO from 4 academic centers in 3
countries were included. Technical success was defined as successful creation of
a gastrojejunostomy. Clinical success was defined as the ability to tolerate a
diet postprocedure. RESULTS: Data were collected on 54 patients. A total of 25
patients underwent EUS-GJ (male n=11, mean age 63.9 y) and 29 patients underwent
Lap-GJ (male n=22, mean age 75.8 y). Technical success was achieved in 29 (100%)
Lap-GJ group patients and 23 (88%) in the EUS-GJ group (P=0.11). AEs occurred in
41% (n=12) of patients in the Lap-GJ group and 12% (n=3) in the EUS-GJ group
(P=0.0386). According to the Clavien-Dindo Classification, the Lap-GJ group AEs
were grade I (n=4), grade II (n=5), grade III (n=2), and grade V (n=1); the EUS
GJ AEs were grade II (n=2) and grade V (n=1). CONCLUSIONS: Although the EUS-GJ
group contained more complex patients, efficacy was similar between the groups.
AEs were significantly lower in the EUS-GJ group. EUS-GJ is a safe and
efficacious, minimally invasive option for patients with GOO.
PMID- 28697152
TI - Transcutaneous Endoscopic Necrosectomy for Walled-off Pancreatic Necrosis in the
Paracolic Gutter.
AB - BACKGROUND: Walled-off pancreatic necrosis (WON) is a sequelae of acute
pancreatitis that requires debridement, once infected. Recently, endoscopic
necrosectomy has become the mainstay for management. However, peripancreatic
collections that extend to the paracolic gutter or lesser sac, are more
challenging to treat endoscopically. We report an endoscopic method for
management of necrotic collections that extend into the paracolic gutter.
METHODS: Consecutive patients, with symptomatic WON extending into the
retroperitoneum, were included in a prospective registry. Each patient underwent
transcutaneous endoscopic necrosectomy (TEN) through a fully covered self
expanding esophageal metal stent. After resolution of the collection, the
external stent was removed, and the cutaneous fistula was allowed to close by
secondary intention. Clinical success was defined as resolution of the WON, and
successful removal of all percutaneous drains. Patient demographics,
procedural/periprocedural adverse events, and follow-up data, were collected.
RESULTS: Nine patients underwent direct TEN. Patients initially underwent CT
guided percutaneous drainage, with an average of 31 days between initial drainage
and endoscopic necrosectomy. All patients had a technically successful placement
of a fully covered esophageal metal stent through the cutaneous fistula. After a
median of 3 endoscopic debridement sessions, 8 of 9 (89%) patients had successful
removal of all percutaneous drains, and resolution of necrotic collections. One
patient died of multisystem organ failure from severe acute pancreatitis.
CONCLUSIONS: TEN for infected WON is a safe and efficacious technique for
patients with endoscopically inaccessible collections.
PMID- 28697153
TI - Mucin Expression in the Esophageal Malignant and Pre-malignant States: A
Systematic Review and Meta-analysis.
AB - BACKGROUND: Mucins are heavily glycosylated glycoproteins, synthesized by mucosal
surfaces and have an important role in healthy state and malignant diseases.
Change in mucins synthesis or secretion may be primary event or secondary to
inflammation or carcinogenesis. AIM: The aim of this study is to assess the
current knowledge about mucin expression in esophageal lesions, and to establish
a role for different mucin expressions as prognostic markers. METHOD: English
Medical literature searches were conducted for "mucin" and "esophagus."
Observational studies were included. Meta-analysis was performed using
comprehensive meta-analysis software. Pooled odds ratios (OR) and 95% confidence
intervals (CI) were calculated. RESULTS: In the random-effect model, mucin
expression was significantly higher in esophageal lesions than in normal
esophageal mucosa with OR=5.456 (95% CI, 1.883-15.807, P=0.002). Measure of
heterogeneity, demonstrated in the included studies, was high: Q=287.501, df
(Q)=44.00, P<0.0001, I=84.696%. There is a gradient of mucin expression and
complexity in esophageal premalignant to malignant lesions, lower in Barrett's
mucosa with low grade dysplasia (LGD), increased in high grade dysplasia (HGD),
and highest in esophageal adenocarcinoma (EAC). MUC2, MUC3, MUC5AC, and MUC6
expression was higher in EAC than HGD, and higher in HGD than in LGD mucosa. The
opposite was found for MUC1 and MUC4. CONCLUSION: Increased expression of certain
mucin genes in esophageal mucosa may be further studied as a potential diagnostic
tool, and this may add important information in the surveillance of Barrett's
esophagus.
PMID- 28697154
TI - Interfacility Transport Shock Index Is Associated With Decreased Survival in
Children.
AB - BACKGROUND: Shock index, the ratio of heart rate to systolic blood pressure that
changes with age, is associated with mortality in adults after trauma and in
children with sepsis. We assessed the utility of shock index to predict sepsis
diagnosis and survival in children requiring interfacility transport to a
tertiary care center. METHODS: We studied children aged 1 month to 21 years who
had at least 2 sets of vital signs recorded during interfacility transport to the
Children's Hospital of Pittsburgh by our critical care transport team. Subjects
were divided into 4 age groups: group 1 (<1 year), group 2 (1-3 years), group 3
(4-11 years), and group 4 (>=12 years). Children were also grouped into sepsis or
nonsepsis group based on the International Classification of Diseases, Ninth
Revision categories. Primary outcome was survival to hospital discharge. RESULTS:
Of 3519 children studied, 493 (14%) had sepsis. Initial shock index decreased
with increasing age: group 1, 1.45 +/- 0.42 (mean +/- SD); group 2, 1.35 +/-
0.32; group 3, 1.20 +/- 0.34; and group 4, 1.00 +/- 0.32 (P < 0.001). Initial
shock index was increased in children with sepsis versus those with no sepsis
overall and in all age groups (all P < 0.05). Initial shock index showed a trend
for association with survival in univariate analysis (P = 0.05) but was not
associated with survival in a multivariable logistic regression. Highest quartile
of shock index was associated with need for intensive care unit admission
posttransport. CONCLUSIONS: Increased shock index in children requiring
intrafacility transport was associated with hospital discharge diagnosis of
sepsis but not hospital survival.
PMID- 28697155
TI - Effect of a Training Strategy in Improving Medication Fallacies During Pediatric
Cardiopulmonary Resuscitation: A Before-and-After Study From a Developing
Country.
AB - OBJECTIVE: This study aims to evaluate the effect of structured training on
resident performance in improving medication fallacies during pediatric
cardiopulmonary resuscitation (CPR). METHODS: This before-and-after study was
conducted in the pediatric acute care areas of tertiary care teaching hospitals
of a developing country from August to December 2015. Case records of children
younger than 18 years who underwent CPR were reviewed. Senior residents rotating
through pediatric emergency department and pediatric intensive care unit were
evaluated for their knowledge. Incidence of medication fallacies in pediatric CPR
and change in the knowledge scores of residents posted in these areas were the
main outcome measures. RESULTS: One-hundred records were evaluated (pre
intervention, 54; post-intervention, 46). In the pre-intervention period, 25 had
medication fallacies (documentation, 16; dosing, 9). In the post-intervention
period, 7 fallacies pertaining to documentation (not dosing) were found. The
incidence of severe fallacies decreased from 20% pretraining to 0% posttraining.
The mean (SD) knowledge scores of residents increased from 7.9 (2.9) pretraining
to 13 (1.4) posttraining. On univariate analysis, fallacies were found to be less
if the resident was formally trained (pediatric advanced life support certified),
if the patient was older, and during morning and night shifts as compared with
evening shift. On multivariate analysis, however, only status of training
(posttraining) (adjusted odds ratio, 0.12; 95% confidence interval, 0.02-0.68)
and the morning shift (adjusted odds ratio, 0.03; 95% confidence interval, 0.001
0.72) remained significant with lower incidence of fallacies associated with
these variables. CONCLUSIONS: Rates of medication fallacies in pediatric CPR
declined with structured training. Documentation fallacies may not be eliminated
completely with only 1-time training.
PMID- 28697156
TI - Transitions of Care: The Presence of Written Interfacility Transfer Guidelines
and Agreements for Pediatric Patients.
AB - OBJECTIVE: Every year, emergency medical services agencies transport
approximately 150,000 pediatric patients between hospitals. During these
transitions of care, patient safety may be affected and contribute to adverse
events when important clinical information is missing, incomplete, or inaccurate.
Written interfacility transfer policies are one way to standardize procedures and
facilitate communication between the hospitals leading to improved patient safety
and satisfaction for children and families. METHODS: We assessed the presence and
components of written interfacility transfer guidelines and agreements for
pediatric patients via a survey sent to US hospital emergency department (ED)
nurse managers during 2010 and 2013. RESULTS: Although there was an increase in
the presence of written interfacility transfer guidelines and agreements, a third
of hospitals did not have either by 2013, and only 50% had guidelines with all
recommended pediatric components. Hospitals with medium and low ED pediatric
patient volumes were less likely to have written guidelines or agreements
compared with hospitals with high volume. Hospitals with advanced pediatric
resources, such as a pediatric emergency care coordinator or EDs designated
approved for pediatrics, were more likely to have guidelines or agreements than
less resourced hospitals. CONCLUSIONS: Although there was improvement over time,
opportunities exist for increasing the presence of written interfacility transfer
guidelines as well as agreements for pediatric patients. Further studies are
needed to demonstrate whether improved delivery of patient care is associated
with the presence of written interfacility transfer guidelines and agreements and
to identify other elements in the process to ensure optimal pediatric patient
care.
PMID- 28697157
TI - Reliability of Smartphone-Based Instant Messaging Application for Diagnosis,
Classification, and Decision-making in Pediatric Orthopedic Trauma.
AB - OBJECTIVE: Smartphones have the ability to capture and send images, and their use
has become common in the emergency setting for transmitting radiographic images
with the intent to consult an off-site specialist. Our objective was to evaluate
the reliability of smartphone-based instant messaging applications for the
evaluation of various pediatric limb traumas, as compared with the standard
method of viewing images of a workstation-based picture archiving and
communication system (PACS). METHODS: X-ray images of 73 representative cases of
pediatric limb trauma were captured and transmitted to 5 pediatric orthopedic
surgeons by the Whatsapp instant messaging application on an iPhone 6 smartphone.
Evaluators were asked to diagnose, classify, and determine the course of
treatment for each case over their personal smartphones. Following a 4-week
interval, revaluation was conducted using the PACS. Intraobserver agreement was
calculated for overall agreement and per fracture site. RESULTS: The overall
results indicate "near perfect agreement" between interpretations of the
radiographs on smartphones compared with computer-based PACS, with kappa of 0.84,
0.82, and 0.89 for diagnosis, classification, and treatment planning,
respectively. Looking at the results per fracture site, we also found substantial
to near perfect agreement. CONCLUSIONS: Smartphone-based instant messaging
applications are reliable for evaluation of a wide range of pediatric limb
fractures. This method of obtaining an expert opinion from the off-site
specialist is immediately accessible and inexpensive, making smartphones a
powerful tool for doctors in the emergency department, primary care clinics, or
remote medical centers, enabling timely and appropriate treatment for the injured
child. This method is not a substitution for evaluation of the images in the
standard method over computer-based PACS, which should be performed before final
decision-making.
PMID- 28697158
TI - How Accurate Are Pediatric Emergency Tapes? A Comparison of 4 Emergency Tapes
With Different Length-Based Weight Categorization.
AB - OBJECTIVE: Pediatric emergency tapes have been developed to support paramedics
and emergency physicians when dosing drugs and selecting medical equipment in
pediatric emergency situations. The aim of this study was to compare the accuracy
of 4 pediatric emergency tapes to correctly estimate patient's weight based on a
large population of patients. METHODS: Patients undergoing general anesthesia
between January 2012 and March 2015 with documented age, sex, body weight, and
length were identified from the electronic anesthesia patient data management
system of the Department of Anaesthesia, University Children's Hospital, Zurich,
Switzerland. Weight estimation by means of the Broselow-Tape, the Padiatrisches
Notfalllineal, the Paulino System, and the Kinder-Sicher were compared with true
patient's weight. Percentages of estimated body weight within a +/-10% and +/-20%
interval were calculated. Data are median (interquartile range) or count
(percent); statistical calculations were done with McNemar and Bonferroni
correction. RESULTS: A total of 3307 patients were identified with complete data
sets, 1930 (58.4%) were male, median age was 4.1 years (1.1-8.2 years), median
length 101.0 cm (74.0-126.0 cm) and median patient weight 15.8 kg (9.2-25.0 kg).
The proportion weight estimation within the +/-10% and the +/-20% interval was
the highest in the Broselow-Tape with 54.0% and 81.5% (P < 0.001 and P = 0.003),
followed by the Padiatrisches Notfalllineal (50.5% and 79.8%), Paulino System
(49.9% and 78.0%) and Kinder-Sicher (48.2% and 77.5%). CONCLUSIONS: The overall
accuracy of all 4 emergency tapes tested is poor and including a larger number of
weight categories does not necessarily increase accuracy. Other strategies have
to be developed to improve weight estimation in pediatric emergency situations.
PMID- 28697159
TI - Outpatient Parenteral Antimicrobial Therapy and Judicious Use of Pediatric
Emergency Resources.
AB - BACKGROUND: Pediatric returns to the emergency department (RTED) vary between 3%
and 13% of the total ED volume of visits. However, the incidence and contribution
of scheduled RTED on pediatric emergency department (PED) utilization is less
clear. Antimicrobial stewardship programs on inpatient wards have been shown to
improve judicious use of outpatient parenteral antimicrobial therapy (OPAT) in
upon discharge. The implementation of such programs in PEDs has yet to be
reported. The objectives of this study are to quantify the burden of scheduled
RTED for OPAT on PED utilization and to examine how frequently OPAT use are
supported by published practice standards for 3 common pediatric infections
cellulitis, pneumonia, and urinary tract infections. METHODS: We conducted a
single-center retrospective cohort study of all visits made to the British
Columbia Children's Hospital PED from May 1, 2012, to April 30, 2013. We
identified scheduled RTEDs and characterized those associated with OPAT use with
regard to their measures of PED utilization and clinical features. RESULTS: Of
3904 RTED visits, 1310 (33.6%) were scheduled, of which 1029 were OPAT related.
Among the latter, 749 RTEDs (69%) were for cellulitis, pneumonia, or urinary
tract infections. The median length of stay for OPAT-related RTEDs was 2.0 hours.
For 75 (24%) of 317 index visits and 213 (28%) of 749 subsequent RTEDs, oral
antibiotic therapy would have been an appropriate option and OPAT could have been
avoided. CONCLUSIONS: Our findings suggest that OPAT poses a sizable burden on
PED utilization, with a proportion of them potentially preventable.
PMID- 28697160
TI - Severe Infant Rash Resistant to Therapy Due to Zinc Deficiency.
AB - Pediatric skin diseases are a common presenting complaint to emergency medicine
physicians but often pose a significant diagnostic challenge. Skin eruptions that
are unusually severe for the diagnosis in question, lasting beyond the typical
time of resolution, or not responding to conventional therapy should raise
concern of a misdiagnosis. We present the case of a severe rash not responding to
conventional atopic dermatitis therapy that led to a diagnosis of transient
neonatal zinc deficiency. Clinicians caring for children should be aware of zinc
deficiency and its corresponding clinical presentation, because it is readily
treatable and may lead to the avoidance of unnecessary treatments and prevention
of serious complications.
PMID- 28697161
TI - Why an On-site Inpatient Pediatric Psychiatric Unit Is Needed to Improve Mental
Health Care in the Pediatric Emergency Department of Lenval Hospital, Nice,
France.
PMID- 28697162
TI - Pediatric Orbeez Ingestions Reported to Texas Poison Centers.
AB - OBJECTIVES: There is concern that ingestion of superabsorbent polymer toys, which
can absorb large amounts of fluid and increase greatly in volume, may pose a risk
if swallowed by children.The intent of this study was to characterize pediatric
Orbeez ingestions reported to a statewide poison center system. METHODS: Cases
were Orbeez ingestions among patients 19 years or younger reported to Texas
poison centers during January 2011 to June 2016. The distribution by various
demographic and clinical factors was determined. RESULTS: Of 110 total cases, 56%
were female and 55% were 5 years or younger. Eighty-six percent of the ingestions
were unintentional. Sixty-nine percent occurred at the patient's home and 28% at
school. Seventy-eight percent of the patients were managed on site. The reported
adverse effects were vomiting (4%), abdominal pain (3%), constipation (1%),
diarrhea (1%), and fever (1%). The reported treatments were dilution (42%), food
or snack (16%), other emetics (1%), whole bowel irrigation (1%), antihistamines
(1%), and intravenous fluids (1%). CONCLUSIONS: Pediatric Orbeez ingestions
tended to involve younger children, were unintentional, and occurred at the
child's home or school. Most ingestions were managed outside of a healthcare
facility. This study provides further evidence that ingestion of Orbeez by
children is not likely to result in serious problems, such as intestinal
obstruction. The information in this investigation may assist in prevention and
education activities.
PMID- 28697163
TI - Utility of Lumbar Puncture in Children Presenting With Status Epilepticus.
AB - OBJECTIVES: Because meningitis may trigger seizures, we sought to determine its
frequency in children with first-time status epilepticus (SE). METHODS: We
performed a retrospective cross-sectional study of children aged 1 month to 21
years who presented to a single pediatric emergency department between 1995 and
2012 with SE and who had a lumbar puncture (LP) performed as part of the
diagnostic evaluation. We defined bacterial meningitis as a cerebrospinal fluid
(CSF) culture positive for a bacterial pathogen or CSF pleocytosis (CSF white
blood cells >=10 cells/mm) with a blood culture positive for a bacterial
pathogen. We defined viral meningitis or encephalitis using a positive
enterovirus or herpes simplex virus polymerase chain reaction test. RESULTS:
Among 126 children with SE who had an LP performed, 8 (6%) had CSF pleocytosis.
Of these, 5 had received antibiotics before performance of a diagnostic LP. One
child in the cohort was proven to have bacterial meningitis (0.8%; 95% confidence
interval [CI], 0%-6%). Two other children had enteroviral meningitis (2/13
tested, 15%; 95% CI, 3%-51%), and 1 had a herpes simplex virus infection (1/47,
2%; 95% CI, 0%-15%). CONCLUSIONS: Bacterial meningitis is an uncommon cause of
SE.
PMID- 28697164
TI - The Use, Safety, and Efficacy of Olanzapine in a Level I Pediatric Trauma Center
Emergency Department Over a 10-Year Period.
AB - OBJECTIVES: Olanzapine is a second-generation antipsychotic increasingly used in
emergency medicine for many indications. Literature on its use in children is
sparse. Our objectives were to describe the use, safety, and efficacy of
olanzapine in pediatric emergency patients. METHODS: A structured chart review
was performed of patients 18 years old or younger receiving olanzapine from 2007
to 2016 in the emergency department of a pediatric level I trauma center.
RESULTS: A total of 285 children received olanzapine. Mean age was 16.4 years
(range, 9-18 years); 121 were male (42.8%). Primary indications for olanzapine
included agitation (n = 166, 58.3%), headache (n = 58, 20.4%),
nausea/vomiting/abdominal pain (n = 37, 12.5%), unspecified pain (n = 20, 7%),
and other (n = 4, 1.4%). Route of olanzapine administration was intramuscular (n
= 160, 56%; median dose, 10 mg; range, 2.5-20), intravenous (n = 101, 36%; median
dose, 5 mg; range, 1.25-5), and oral (n = 24, 8%; median dose, 10 mg; range, 5
10). For agitated patients, 28 (17%) received another sedative within 1 hour. For
headache patients, 5 (8.6%) received another analgesic. For gastrointestinal
complaints, 5 patients (13.5%) received another analgesic/antiemetic. Adverse
respiratory events were hypoxia (pulse oximetry reading, in percentage, <92%; n =
7, 2.4%), supplemental oxygen placement (n = 9, 3.2%), and intubation (n = 2,
0.7%). No patient died or had a dysrhythmia. One patient experienced dystonia.
CONCLUSIONS: Olanzapine seems safe when used for a variety of conditions in
pediatric emergency patients. It may be effective for acute agitation, primary
headache, and gastrointestinal complaints.
PMID- 28697165
TI - Association of CYP3A5 Expression and Vincristine Neurotoxicity in Pediatric
Malignancies in Turkish Population.
AB - Vincristine is a widely used chemotherapeutic agent in the treatment of childhood
malignancies. Neuropathy is the most common adverse effect. CYP3A4 and CYP3A5
enzymes of cytochrome p450 enzyme system are responsible in vincristine
metabolism. Genetic polymorphism may alter the vincristine metabolism and the
neurotoxicity rate. In this study, distribution of CYP3A5 alleles among Turkish
children with malignancies, relation between CYP3A5 genotype and neurotoxicity
rates, as well as severity and duration of neuropathy and total vincristine doses
were investigated. Patient group consisted of 115 patients (age, 1 to 17 y) with
acute lymphoblastic leukemia and solid tumors, who were treated with vincristine
consisting chemotherapy protocols. Control group consisted of 50 children without
any neurological symptom or disorders. All patient files were reviewed for
presence and severeness of neurotoxicity symptoms. Blood samples were obtained
and CYP3A5 genotypes were analyzed. Neurotoxicity occurred in 20.8% of patients.
Although it was found to occur more frequently after 4 doses of vincristine, and
rates were higher in the low-dose vincristine group suggesting other contributing
factors. Although neurotoxicity rate in the CYP3A5*1/*3 genotype was 17.6%, it
was 21.6% in the CYP3A5*3/*3 genotype and the difference was not statistically
significant (P<0.05). This study suggested that vincristine-related neurotoxicity
is dose-independent and genotype is not the only causative factor in the
occurrence of neurotoxicity in these patients.
PMID- 28697166
TI - Cytomegalovirus Cavitary Pneumonia in Nontransplant Pediatric Acute Lymphoblastic
Leukemia: Case Report and Review of the Literature.
AB - Lung cavitary lesions are a rare finding in the nontransplant setting of a
patient with acute leukemia. Among viral agents, cytomegalovirus (CMV) may cause
pulmonary nodules and cavities in patients undergoing hematopoietic stem cell
transplantation, but during pediatric acute lymphoblastic leukemia treatment, CMV
disease is less common. Here we report the case of a boy affected by acute
lymphoblastic leukemia who suffered severe cavitary CMV pneumonia during
chemotherapy, and we review the current literature.
PMID- 28697167
TI - Congenital Amegakaryocytic Thrombocytopenia: A Case Series Indicating 2 Founder
Variants in the Mississippi Band of Choctaw Indians.
AB - Congenital amegakaryocytic thrombocytopenia is a rare disorder causing
thrombocytopenia that progresses to pancytopenia and bone marrow failure if
untreated. It is caused by variants in the MPL gene which encodes the
thrombopoeitin receptor. In this report, we review 5 cases of congenital
amegakaryocytic thrombocytopenia, all of whom belong to the Mississippi Band of
Choctaw Indians. There are 2 common variants in these cases: R90X and R537W. One
variant was previously reported only once and had unclear significance at that
time. With these variants identified, we hope to improve screening that results
in earlier diagnosis in the Choctaw population in the future.
PMID- 28697168
TI - Pretreatment Neutrophil-to-Lymphocyte Ratio and Lymphocyte Recovery: Independent
Prognostic Factors for Survival in Pediatric Sarcomas.
AB - BACKGROUND: Pretreatment neutrophil-to-lymphocyte ratio (NLR) and absolute
lymphocyte count (ALC) recovery have been shown to be associated with prognosis
in several types of cancer in adults. However, evidence in pediatric cancer is
scarce. The aim of our study was to evaluate whether pretreatment NLR and
lymphocyte recovery are prognostic factors in pediatric sarcomas. MATERIALS AND
METHODS: Study participants were identified from a retrospective cohort of 100
children with osteosarcoma (n=55), rhabdomyosarcoma (n=22), and Ewing sarcoma
(n=23). Data for the hematological variables were obtained from medical records
and analyzed with other known prognostic factors in univariate and multivariate
analyses. RESULTS: In multivariate analysis, NLR>2 was an independent prognostic
factor for OS in patients with osteosarcoma (hazard ratio [HR], 2.27, 95%
confidence interval [CI], 1.07-5.30; P=0.046) along with metastatic disease and
poor histologic response; as well as in patients with rhabdomyosarcoma (HR, 4.76,
95% CI, 1.01-22.24; P=0.0237) along with metastatic disease and risk group. ALC
recovery correlated for inferior OS in osteosarcoma (HR, 3.34, 95% CI, 1.37-8.12;
P=0.008) and rhabdomyosarcoma (HR, 3.89; 95% CI, 1.01-14.89; P=0.0338).
CONCLUSIONS: Our study confirms that NLR and ALC recovery are independent
prognostic factors for pediatric sarcomas, implying an important role of immune
system in survival. Clinical utility of these prognostic biomarkers should be
validated in larger pediatric studies.
PMID- 28697169
TI - Systemic Epstein-Barr Virus-positive T-Cell Lymphoproliferative Disease of
Childhood With Good Response to Steroid Therapy.
AB - Systemic Epstein-Barr virus (EBV)-positive T-cell lymphoproliferative disease of
childhood is a rare disease and has a very fulminant clinical course with high
mortality. A 21-month-old female patient was referred to our hospital with a 1
week history of fever and was subsequently diagnosed with systemic Epstein-Barr
virus-positive T-cell lymphoproliferative disease of childhood. After starting
treatment with dexamethasone, she showed early defervescence and improvement of
laboratory parameters, and has remained disease-free after stopping steroid
treatment, although longer follow-up is necessary. Our report underscores the
possibility that this disease entity may be heterogenous in terms of prognosis.
PMID- 28697170
TI - Critically Ill Children With Hemophagocytic Lymphohistiocytosis: A Case Series of
14 Patients.
AB - Children with hemophagocytic lymphohistiocytosis (HLH) are at an increased risk
of critical illness. In this study, we described the clinical characteristics of
critically ill children with HLH and identify factors associated with poor
clinical outcomes. Children who were diagnosed with HLH with emergent admission
to Children's Intensive Care Unit (CICU) between January 1, 2000 and October 31,
2015 were included. The primary outcome was CICU mortality. Over the 15-year
period, there were 14 critically ill patients with HLH with 23 CICU admissions.
Median age at HLH diagnosis was 8.2 years (interquartile range [IQR], 2.9 to
11.3). Overall CICU mortality was 8 of 23 CICU admissions (34.8%). Factors that
were associated with CICU mortality in critically ill children with HLH
identified in this study include: a worse median pediatric index of mortality 2
score (4.7% in survivors [IQR, 2.9% to 11.6%] vs. 2.4% [IQR, 1.2% to 4.3%];
P=0.031); higher median peak serum lactate level (mmol/L) within 24 hours of
admission (5.6 [IQR, 2.7 to 17.4] vs. 1.6 [IQR, 1.2 to 2.8]; P=0.032); the need
for mechanical ventilation (100% vs. 46.7%; P=0.019); inotropic support (87.5%
vs. 20.0%; P=0.006); renal replacement therapy (50% vs. 0%; P=0.008); and blood
product transfusion episodes (24.5 [IQR, 14.3 to 46.8] vs. 3.0 [IQR, 1.0 to 9.0];
P=0.002). Further studies are required to validate the factors that are
associated with poor outcomes in critically ill children with HLH.
PMID- 28697171
TI - Variability in Imaging Practices and Comparative Cumulative Effective Dose for
Neuroblastoma and Nephroblastoma Patients at 6 Pediatric Oncology Centers.
AB - The purpose of this study was to estimate the cumulative effective dose (CED)
from diagnosis and posttherapy computed tomographic (CT) scans performed on
children treated for neuroblastoma or nephroblastoma (Wilms tumor) and to examine
the different imaging practices used in 6 regional pediatric oncology centers
between January 2010 and December 2013. We analyzed retrospectively the CT scan
acquisition data in children aged 10 years or younger at diagnosis. The use of
nonionizing imaging modalities was reported. The CT examinations of 129 children,
with a mean age at diagnosis of 36 months, treated for 66 neuroblastomas and 63
nephroblastomas, were analyzed. The mean follow-up period was 28 months (minimum,
8 months, maximum, 41 mo). There were 600 CT scans, with a total of 1039
acquisitions. The mean CED from CT scans was 27 mSv (minimum=18.25, maximum=45).
Abdominal CT examinations contributed 85% of the total CED. A median of 4.6 CT
scans, 10.3 sonograms, and 0.4 magnetic resonance imaging examinations per child
were performed. Our results suggest a reduction in radiation exposure but
variability in the imaging modality choice and acquisition protocols. We
emphasize the need for consensus and standardization in oncologic pediatric
imaging procedures. When feasible, we encourage the substitution of nonionizing
examinations for CT.
PMID- 28697172
TI - Immunogenic Chemotherapy Sensitizes Renal Cancer to Immune Checkpoint Blockade
Therapy in Preclinical Models.
AB - BACKGROUND Renal cell carcinoma (RCC) is among the most common malignant cancers
of males worldwide. For advanced RCC patients, there still is no effective
therapy. Immune checkpoint blockade therapies have shown benefits for many
cancers, but previous clinical trials of immune checkpoint blockade therapies in
RCC patients achieved only modest results. MATERIAL AND METHODS We explored the
effects of combining chemotherapy with immune checkpoint blockade therapy in RCC
xenograft mouse models. We also studied the potential mechanisms by which
chemotherapy might enhance the efficacy of immune checkpoint blockade therapy,
both in vitro and in vivo. RESULTS Our results showed that many commonly used
chemotherapy agents can induce immunogenic marker release in RCC cell lines.
Importantly, the RCC xenograft mouse model mice who received the combination
treatment of 5-fluorouracil (5-FU) and anti-programmed cell death-ligand 1 (PD
L1) antibodies (Abs) had longer survival times compared to those who received 5
FU or anti-PD-L1 Abs alone. Also, increased key cytokines that promote tumor
immunity, such as IL-2, IFN-gamma, and TNF-alpha, as well as tumor-infiltrating
cytotoxic T cells, were also increased after the combination treatment.
CONCLUSIONS We conclude that 5-FU can sensitize RCC to anti-PD-L1 treatment by
releasing the immune suppression in the tumor microenvironment.
PMID- 28697173
TI - Modulating cancer cell survival by targeting intracellular cholesterol transport.
AB - BACKGROUND: Demand for cholesterol is high in certain cancers making them
potentially sensitive to therapeutic strategies targeting cellular cholesterol
homoeostasis. A potential approach involves disruption of intracellular
cholesterol transport, which occurs in Niemann-Pick disease as a result of acid
sphingomyelinase (ASM) deficiency. Hence, a class of lysosomotropic compounds
that were identified as functional ASM inhibitors (FIASMAs) might exhibit
chemotherapeutic activity by disrupting cancer cell cholesterol homoeostasis.
METHODS: Here, the chemotherapeutic utility of ASM inhibition was investigated.
The effect of FIASMAs on intracellular cholesterol levels, cholesterol
homoeostasis, cellular endocytosis and signalling cascades were investigated. The
in vivo efficacy of ASM inhibition was demonstrated using melanoma xenografts and
a nanoparticle formulation was developed to overcome dose-limiting CNS-associated
side effects of certain FIASMAs. RESULTS: Functional ASM inhibitors inhibited
intracellular cholesterol transport leading to disruption of autophagic flux,
cellular endocytosis and receptor tyrosine kinase signalling. Consequently, major
oncogenic signalling cascades on which cancer cells were reliant for survival
were inhibited. Two tested ASM inhibitors, perphenazine and fluphenazine that are
also clinically used as antipsychotics, were effective in inhibiting xenografted
tumour growth. Nanoliposomal encapsulation of the perphenazine enhanced its
chemotherapeutic efficacy while decreasing CNS-associated side effects.
CONCLUSIONS: This study suggests that disruption of intracellular cholesterol
transport by targeting ASM could be utilised as a potential chemotherapeutic
approach for treating cancer.
PMID- 28697174
TI - UV radiation promotes melanoma dissemination mediated by the sequential reaction
axis of cathepsins-TGF-beta1-FAP-alpha.
AB - BACKGROUND: Ultraviolet radiation (UVR) is the major risk factor for development
of malignant melanoma. Fibroblast activation protein (FAP)-alpha is a serine
protease expressed on the surface of activated fibroblasts, promoting tumour
invasion through extracellular matrix (ECM) degradation. The signalling mechanism
behind the upregulation of FAP-alpha is not yet completely revealed. METHODS:
Expression of FAP-alpha was analysed after UVR exposure in in vitro co-culture
systems, gene expression arrays and artificial skin constructs. Cell migration
and invasion was studied in relation to cathepsin activity and secretion of
transforming growth factor (TGF)-beta1. RESULTS: Fibroblast activation protein
alpha expression was induced by UVR in melanocytes of human skin. The FAP-alpha
expression was regulated by UVR-induced release of TGF-beta1 and cathepsin
inhibitors prevented such secretion. In melanoma cell culture models and in a
xenograft tumour model of zebrafish embryos, FAP-alpha mediated ECM degradation
and facilitated tumour cell dissemination. CONCLUSIONS: Our results provide
evidence for a sequential reaction axis from UVR via cathepsins, TGF-beta1 and
FAP-alpha expression, promoting cancer cell dissemination and melanoma metastatic
spread.
PMID- 28697175
TI - Platelet releasate promotes breast cancer growth and angiogenesis via VEGF
integrin cooperative signalling.
AB - BACKGROUND: Selective platelet release of pro- or anti-angiogenic factors
distinctly regulated angiogenesis. We hypothesised that selective release of
platelet angiogenic factors could differently regulate tumour growth. METHODS:
Breast cancer cell proliferation, cancer cell-induced endothelial tube formation
in vitro, and tumour growth in vivo were studied in the presence of protease
activated receptor 1-stimulated platelet releasate (PAR1-PR; rich in pro
angiogenic factors) or PAR4-PR (rich in anti-angiogenic factors). RESULTS: The
PAR1-PR and PAR4-PR supplementation (10%) similarly enhanced cell proliferation
of MCF-7 and MDA-MB-231 breast cancer cells. The cancer cells triggered capillary
like tube formation of endothelial cells that was further enhanced by pro
angiogenic factor-rich PAR1-PR. The VEGF, but not SDF-1alpha, receptor blockade
abolished PAR1-PR/PAR4-PR-enhanced cancer cell proliferation. Integrin blockade
by RGDS had identical effects as VEGF inhibition. The Src and ERK inhibition
diminished, whereas PI3K and PKC blockade abolished platelet releasate-enhanced
cancer cell proliferation. Using a model of subcutaneous implantation of MDA-MB
231 cells in nude mice, PAR1-PR enhanced tumour growth more markedly than PAR4
PR, and seemed to achieve the exaggeration by promoting more profound tumour
angiogenesis. CONCLUSIONS: Platelet releasate increases breast cancer cell
proliferation through VEGF-integrin cooperative signalling. Pro-angiogenic factor
rich platelet releasate enhances cancer cell-induced angiogenesis more markedly,
and thus exaggerates tumour growth in vivo.
PMID- 28697176
TI - HMGA1 expression levels are elevated in pancreatic intraepithelial neoplasia
cells in the Ptf1a-Cre; LSL-KrasG12D transgenic mouse model of pancreatic cancer.
AB - BACKGROUND: Pancreatic cancer is currently the third leading cause of cancer
deaths in the United States and it is predicted to become the second by the year
2030. High-mobility group A1 protein (HMGA1) is an oncogenic transcription
factor, localised and active in cell nuclei, that is linked to tumour progression
in many human cancers, including pancreatic cancer. Overexpression of HMGA1
renders cancer cells resistant to chemotherapy. Although the Ptf1a-Cre; LSL
KrasG12D transgenic mouse is perhaps the most widely utilised animal model for
human pancreatic cancer, expression levels of HMGA1 in pancreata from this mouse
model have not been characterised. METHODS: Quantitative immunohistochemical
analysis was used to determine nuclear HMGA1 levels in pancreatic tissue sections
from Ptf1a-Cre; LSL-KrasG12D mice aged 5, 11, and 15 months. The H Score method
was used for quantitative analysis. RESULTS: The HMGA1 levels were significantly
elevated in pancreatic intraepithelial neoplasia (PanIN) epithelia compared with
untransformed acinar tissues or fibroinflammatory stroma. CONCLUSIONS: The PanINs
have long been regarded as precancerous precursors to pancreatic adenocarcinoma.
Significantly elevated HMGA1 levels observed in the nuclei of PanINs in Ptf1a
Cre; LSL-KrasG12D mice validate this animal model for investigating the role that
HMGA1 plays in cancer progression and testing therapeutic approaches targeting
HMGA1 in human cancers.
PMID- 28697178
TI - Put to the test: Organoid-based testing becomes a clinical tool.
PMID- 28697177
TI - The TGF-beta signalling negative regulator PICK1 represses prostate cancer
metastasis to bone.
AB - : Backgroud:Constitutive activation of TGF-beta signalling is a well-recognised
mechanism in bone metastasis of prostate cancer (PCa). Protein Interacting with
PRKCA 1 (PICK1) is a critical negative regulator of the TGF-beta pathway.
However, the clinical significance and biological role of PICK1 in PCa bone
metastasis remain obscure. METHODS: PICK1 expression is evaluated by
immunohistochemistry (IHC) in 198 PCa patients. Statistical analysis is performed
to explore correlation between PICK1 expression and clinicopathological features
in PCa patients. The biological role of PICK1 is examined in PC-3 and C4-2B cells
in vitro and a mouse intracardial model in vivo. RESULTS: PICK1 expression is
decreased in PCa tissues with bone metastasis and bone-derived cells and
downregulation of PICK1 positively correlates with serum PSA level, Gleason grade
and bone metastasis status in PCa patients. Overexpression of PICK1 suppresses
PCa cell invasion and migration in vitro and bone metastasis in vivo. Our results
further indicate downregulation of PICK1 is caused by miR-210-3p overexpression
in PCa tissues with bone metastasis. Clinical negative correlation of PICK1 with
miR-210-3p is confirmed in PCa tissues. CONCLUSIONS: Our findings uncover a novel
functionally and clinically relevant epigenetic regulatory mechanism for
constitutive activation of TGF-beta signalling in bone metastasis of PCa.
PMID- 28697179
TI - A mouse model of renal cell carcinoma.
PMID- 28697180
TI - Medicine's movable feast: What jumping genes can teach us about treating disease.
PMID- 28697181
TI - Battling the biology of opioid addiction.
PMID- 28697182
TI - A prescription for cancer diagnostics.
PMID- 28697183
TI - Correction.
PMID- 28697185
TI - An unexpected role for bile acid synthesis in adaptation to low temperature.
PMID- 28697184
TI - Insulin action and resistance in obesity and type 2 diabetes.
AB - Nutritional excess is a major forerunner of type 2 diabetes. It enhances the
secretion of insulin, but attenuates insulin's metabolic actions in the liver,
skeletal muscle and adipose tissue. However, conflicting evidence indicates a
lack of knowledge of the timing of these events during the development of obesity
and diabetes, pointing to a key gap in our understanding of metabolic disease.
This Perspective reviews alternate viewpoints and recent results on the temporal
and mechanistic connections between hyperinsulinemia, obesity and insulin
resistance. Although much attention has addressed early steps in the insulin
signaling cascade, insulin resistance in obesity seems to be largely elicited
downstream of these steps. New findings also connect insulin resistance to
extensive metabolic cross-talk between the liver, adipose tissue, pancreas and
skeletal muscle. These and other advances over the past 5 years offer exciting
opportunities and daunting challenges for the development of new therapeutic
strategies for the treatment of type 2 diabetes.
PMID- 28697186
TI - Whiplash Syndrome- a disorder of the brain?
AB - In the past two decades much has been published on whiplash injury, yet both the
confusion regarding the condition, and the medicolegal discussion about it have
increased. In this paper, functional imaging research results are summarized
using MRIcroGL 3D visualization software and assembled in an image comprising
regions of cerebral activation and deactivation.
PMID- 28697187
TI - Can semiquantitative measurements of SUVmax and cut-off values differentiate
colorectal malignant from benign lessions?
AB - OBJECTIVE: We investigated maximum standardized uptake value (SUVmax) and cut-off
values for differentiation of malignant and benign lesions in colorectal cancer
(CC) as multiple studies have questioned their validity. We also investigated
more extended indices using common semi-quantification analysis in incidental
colorectal findings (ICF). SUBJECTS AND METHODS: Fluorine-18-fluoro deoxy glucose
positron emission tomography/computed tomography in 25 patients with a total of
30 focal ICF was retrospectively analysed using dedicated software. Method
variability was tested through application of three common threshold-based lesion
delineation techniques as well as a partial-volume correction (PVC). Lesion
SUVmax, SUVmean, metabolically active volume (MAV) and mean total lesion
glycolysis (TLG) were thereby extracted along with PVC corrected values
(cSUVmean, cTLG) and SUVpeak. RESULTS: In all lesions, SUVmax was >5 and
SUVmean>=2.7. Malignant SUVmax values (mean+/-SD: 16.5+/-6.2) were overall
significantly higher than benign levels (9.8+/-3.6). There was a substantial
overlap with values in polyps/adenomas (14.4+/-7.7). Both SUVpeak and SUVmean
showed similar characteristics. Malignant MAV and TLG showed more distinct
levels. Though different segmentation methods introduced variations, largest in
MAV (-58.6%-141.5%), and PVC generally increased measures significantly by a
factor of 1.2-2.7, neither changed relative levels much. SUVmax values were
inadequate for aetiological differentiation of ICF, which also precludes a
clinically significant cut-off value. The same applies to SUVpeak and SUVmean
while TLG measures may be more indicative. CONCLUSION: Semi-quantitative
measurements of SUVmax and cut-off values proved inadequate for differentiating
colorectal malignancies from benign findings. While integrated measures, e.g.
cTLG, are potentially better indicators of disease severity and extent, more
optimal segmentation and PVC methods are required.
PMID- 28697188
TI - Impact of tall cell variant histology on predicting relapse and changing the
management of papillary thyroid carcinoma patients.
AB - OBJECTIVE: There has been much discussion recently about the risk category of
tall cell variant (TVC) histology and its effects on the management of papillary
thyroid carcinoma (PTC). We, therefore, undertook a retrospective study to
compare stage-matched risk factors and recurrence rates between classical PTC
(cPTC) patients and patients with TCV histology. SUBJECTS AND METHODS: A total of
3128 well-differentiated thyroid carcinoma patients who were treated and followed
up for more than 5 years in our clinic from 1995 to 2016 were included in this
study. There were 2783 PTC (89%) patients, 1113 (40%) of them were cPTC and 56
(2%) of them were TCV patients. RESULTS: In all stages, the stage-matched
incidence of extrathyroidal extension (ETE), lymphovascular invasion and initial
lymph node metastases were significantly higher in TCV patients than in cPTC
patients (P<0.001). Recurrence was in 10 of 27 patients (37%) with TCV and in 91
of 890 (10%) patients with cPTC diagnosed in stage I (odds ratio (OR)=5.16); in 4
of 6 patients with TCV and 18 of 84 (21%) patients with cPTC in stage II
(OR=7.33); in 5 of 6 patients with TCV and 11 of 46 (23%) patients with cPTC in
stage III (OR=15.90); and in 13 of 17 patients with TCV and 31 of 93 (33%)
patients with cPTC in stage IV (OR=6.50). Stage-matched recurrence rates were
found significantly higher in all stages of TCV patients than in cPTC patients
(OR=8.49, P<0.001). Recurrence with distant metastases was seen more frequently
in TCV patients than in cPTC patients (P<0.001) and treatment of metastatic
disease was more difficult in TCV patients. CONCLUSION: Tall cell variant was an
independent poor prognostic factor in papillary thyroid carcinoma patients even
if they were diagnosed at early stages of the disease. Patients with tall cell
variant histology required more aggressive therapeutic approach and closer follow
up than classical patients.
PMID- 28697189
TI - Gallium-68-dotatate PET/CT is better than CT in the management of somatostatin
expressing tumors: First experience in Africa.
AB - OBJECTIVE: In this study we aimed to present our experience on the use of Gallium
68-dotatate with positron emission tomography, computed tomography (68 Ga
dotatate PET/CT) in the management of neuroendocrine tumors (NET) and other
somatostatin expressing tumors. SUBJECTS AND METHODS: We retrospectively reviewed
patients with histologically confirmed or biochemically suspected NET and other
somatostatin expressing (SSTR) tumors imaged at our department with 68Ga-dotatate
PET/CT. We determined the performance of this imaging technique as well as its
impact on patients management. A total of 203 patients were studied: 103 females,
100 males median age 52years. RESULTS: The commonest tumor type was
gastroenteropancreatic NET (41% of patients) and the commonest sites of distant
metastases were lymph nodes and the liver 34.0% and 30.5% respectively. Positron
emission tomography detected foci of disease in 19 patients where CT was falsely
negative. The sensitivity, specificity, positive predictive value, negative
predictive value and accuracy of 68 Ga-dotatate PET/CT imaging of NET and other
SST expressing tumors were 94.16%, 91.89%, 95.55%, 89.47% and 96.55%
respectively. CONCLUSION: Gallium-68-dotatate PET/CT was better than CT in
detecting primary sites of the disease and highly sensitive and specific for
diagnosis and treatment of NET and other SSTR expressing tumors.
PMID- 28697190
TI - 18F-FDG PET/CT and histology for diagnosing recurrent/remnant tumors in head and
neck cancer patients treated with radiotherapy.
AB - OBJECTIVE: The aim of this study was to assess the diagnostic performance of
fluorine-18-fluoro-2-deoxyglucose (18F-FDG) positron emission tomography
(PET)/computed tomography (CT) for locoregional recurrent/residual tumor in
patients with head and neck cancer (HNC) who underwent previous radiotherapy
(RT). SUBJECTS AND METHODS: 18F-FDG PET/CT images from patients with HNC who
previously underwent RT were retrospectively reviewed. Only cases with
histological confirmation within 4 weeks of PET/CT imaging were included.
Standardized uptake values were obtained for lesions and PET/CT findings were
compared with histological results. RESULTS: Of 181 cases, 114 (63%) were
histologically confirmed as malignant and 67 (37%) as benign. The sensitivity,
specificity, and accuracy of PET/CT were 93%, 64%, and 82%, respectively.
Inflammation was the most common cause of false positives and small tumor volume
and low 18F-FDG avidity were the causes of false negatives. PET/CT had 100%
sensitivity and 56% specificity for detecting recurrent or residual disease
within 12 weeks after RT and 93% sensitivity and 64% specificity, more than 12
weeks after RT. The frequency of false positives in PET/CT images within 12 weeks
of RT was similar to the results obtained 12 weeks after RT (15% vs. 14%). False
positives were more frequent in PET/CT cases after two-dimensional or three
dimensional conformal RT than in those after intensity-modulated RT, although not
statistically significant (15% vs. 9%, p>0.05). CONCLUSION: 18F-FDG PET/CT might
aid the diagnosis of locoregional residual/recurrent tumors in patients with HNC
previously treated with RT. Inflammation was the main cause of false positives
regardless of the interval between RT and PET/CT, even several years after RT.
Therefore, histological verification of positive PET/CT findings should be
conducted during follow-up of HNC patients treated with RT.
PMID- 28697191
TI - An innovative method for precise lymph node detection before surgical treatment
in breast cancer.
AB - OBJECTIVE: To describe a new method of 3D interactive modeling which integrates
images obtained by separate SPET and multi slice computed tomography (MSCT)
modalities using an original software in order to better localize SNL in BC
patients. SUBJECTS AND METHODS: We used technetium-99m-colloid rhenium sulphate
for identifying SNL in seven patients with BC. Markers were made of lead pearls
wrapped with cotton wool soaked in 99mTc-pertechnetate and placed on the skin of
the patients forming of a triangle. Using an original software, two separate 3D
models were made after SPET and MSCT imaging and then merged into a hybrid 3D
model which enabled precise visualization and localization of the SNL. RESULTS:
In all cases the position of the SNL established by our method was successfully
verified using a gamma probe. Duration of SNL identification and extirpation were
significantly reduced in less than 10 minutes per patient. The reproducibility of
this method was confirmed by precise identification and biopsy of the SNL.
CONCLUSION: We found this integrated SPET/MSCT 3D model to be much faster and
easier to use as compared with the "classic" method, which was based on a
radioactivity detection probe. In addition, our method was reproducible, accurate
and of low cost. In other words, the method described in this paper could be very
useful for health facilities with modest budget, because it obviates the need for
buying expensive integrated SPET/MSCT hybrid imaging systems while detecting SNLs
more accurately and in shorter time.
PMID- 28697192
TI - A prototype PET/SPECT/X-rays scanner dedicated for whole body small animal
studies.
AB - OBJECTIVE: To present a prototype tri-modal imaging system, consisting of a
single photon emission computed tomography (SPET), a positron emission tomography
(PET), and a computed tomography (CT) subsystem, evaluated in planar mode.
MATERIALS AND METHODS: The subsystems are mounted on a rotating gantry, so as to
be able to allow tomographic imaging in the future. The system, designed and
constructed by our group, allows whole body mouse imaging of competent
performance and is currently, to the best of our knowledge, unequaled in a
national and regional level. The SPET camera is based on two Position Sensitive
Photomultiplier Tubes (PSPMT), coupled to a pixilated Sodium Iodide activated
with Thallium (NaI(Tl)) scintillator, having an active area of 5x10cm2. The dual
head PET camera is also based on two pairs of PSPMT, coupled to pixelated
berillium germanium oxide (BGO) scintillators, having an active area of 5x10cm2.
The X-rays system consists of a micro focus X-rays tube and a complementary metal
oxide-semiconductor (CMOS) detector, having an active area of 12x12cm2. RESULTS:
The scintigraphic mode has a spatial resolution of 1.88mm full width at half
maximum (FWHM) and a sensitivity of 107.5cpm/0.037MBq at the collimator surface.
The coincidence PET mode has an average spatial resolution of 3.5mm (FWHM) and a
peak sensitivity of 29.9cpm/0.037MBq. The X-rays spatial resolution is 3.5lp/mm
and the contrast discrimination function value is lower than 2%. CONCLUSION: A
compact tri-modal system was successfully built and evaluated for planar mode
operation. The system has an efficient performance, allowing accurate and
informative anatomical and functional imaging, as well as semi-quantitative
results. Compared to other available systems, it provides a moderate but
comparable performance, at a fraction of the cost and complexity. It is fully
open, scalable and its main purpose is to support groups on a national and
regional level and provide an open technological platform to study different
detector components and acquisition strategies.
PMID- 28697193
TI - The value of 18FDG PET/CT parameters, hematological parameters and tumor markers
in predicting KRAS oncogene mutation in colorectal cancer.
AB - OBJECTIVE: In this study we investigated the predictive value of maximum
standardized uptake value (SUVmax), metabolic tumor volume (MTV), total lesion
glycolysis (TLG), neutrophils/lymphocytes ratio (NLR), platelets/lymphocytes
ratio (PLR), carcinoembryonic antigen (CEA) and carbohydrate antigen (CA 19-9) in
the prediction of KRAS gene mutation which plays an important role in the choice
of treatment in colorectal cancer patients. SUBJECTS AND METHODS: A total of 55
cases with untreated colorectal cancer who had undergone both PET/CT examinations
for initial staging and also mutation analysis of KRAS oncogene were studied.
Fluorine-18-FDG PET/CT parameters (SUVmax, MTV, TLG), hematological parameters
(NLR, PLR), and tumor markers (CEA, CA 19-9) were recorded and the relationship
between these parameters and KRAS oncogene mutation was evaluated using receiver
operating characteristics (ROC) analysis and multiple logistic regression
analysis. RESULTS: In 20 cases mutations in the KRAS gene were detected, while in
35 cases mutations were not observed (wild-type). ROC analysis revealed that
SUVmax, MTV, TLG, NLR, PLR, and CA 19-9 could not predict mutations in KRAS
oncogene (P=0.600, 0.263, 0.214, 0.057, 0.104, 0.189, respectively) although CEA
value showed signi..cant difference (P=0.031) but without high value of the area
under the curve (0.676). Multivariate logistic regression analysis also did not
show significant association between KRAS gene mutations and SUVmax, MTV, TLG,
NLR, PLR, CEA, CA 19-9 values. CONCLUSION: We observed that in patients with
colorectal cancers, we cannot predict KRAS gene mutations using PET/CT parameters
(SUVmax, MTV, TLG), hematological parameters (NLR, PLR) or tumor marker CA 19-9.
We detected a significant but not very strong association only between CEA and
KRAS mutations.
PMID- 28697194
TI - Enhancing contrast agents and radiotracers performance through hyaluronic acid
coating in neuroradiology and nuclear medicine.
AB - The use of hyaluronic acid nanoshells has been proposed to encapsulate prodrugs
and exploit the mechanisms of interactions between living cells, like endocytes
or cancer cells and hyaluronic acid, which is a natural component of the
extracellular matrix. In this review we describe the potential and the limits of
this promising research trend and discuss the theoretical advantages of such an
engineering approach. Is it a possible scalability to increase the efficacy and
biodegradability of molecules like contrast media and radiotracers especially for
neuroradiology and nuclear medicine studies.
PMID- 28697195
TI - Fluorine-18-FDG PET/CT in a patient with angiomyolipoma: Response to mammalian
target of rapamycin inhibitor therapy.
AB - We report on a 27 years old female patient who was referred to our department for
whole-body as well as dynamic positron emission tomography/computed tomography
(dPET/CT) scan of the upper and middle abdomen with fluorine-18-fluorodeoxy
glucose (18F-FDG), for further evaluation of a mass in the left adrenal gland
region. Positron emission tomography showed a suspicious, enlarged,
hypermetabolic mass with an average standardized uptake value (SUV) of 4.5 and a
maximum SUV of 5.9. The patient was referred for biopsy, which revealed an
angiomyolipoma, a perivascular epithelioid cell tumor (PEComa) of the adrenal
gland. Perivascular epithelioid cell tumors are mesenchymal tumors consisting of
blood vessels, smooth muscles and fat cells. The patient received anti
proliferative treatment with Afinitor, a mammalian target of rapamycin (mTOR)
inhibitor, and was referred again one month after onset of therapy for early
response assessment. The follow-up 18F-FDG PET/CT scan showed a nearly complete
resolution of the previously detected adrenal mass, with very low tracer uptake
and a decrease in its functional volume. Fluorine- 18-FDG PET/CT can be used for
treatment response evaluation of angiomyolipoma treated with mTOR-inhibitors.
PMID- 28697196
TI - Fluorine-18-fluorodeoxyglucose positron emission tomography/ computed tomography
findings in a pediatric mucoepidermoid carcinoma and differential diagnosis.
AB - An 11 years old boy was referred to our hospital. He complained for the last
three months for intermittent cough and shortness of breath after exercise which
worsened recently. Airways computed tomography (CT) showed an abnormal
endobronchial tumor, obstructing the right main bronchus and also atelectasis in
the upper lobe of the right lung. Bronchoscopy showed a wet on its surface mass
obstructing the right main bronchus. Biopsy showed a mucoepidermoid carcinoma
(MEC). The fluorine-18-fluorodeoxyglucose positron emission tomography/computed
tomography (18F-FDG PET/CT) scan showed in the same area a mass with slightly
increased 18F-FDG uptake (maximum standardized uptake value, SUVmax: 3.8),
without mediastinal lymph nodes involvement. The boy had thoracoscopic resection
of the right upper lobe, right main bronchus and right inferior lobe bronchial
sleeve anastomosis. Histological examination confirmed the diagnosis of a low to
intermediate grade malignant MEC without lymph nodes metastases. The patient has
been well and free from recurrence for 2 years postoperatively.
PMID- 28697197
TI - Increased and normalized uptake of 18F-FDG in a case of bone periprosthetic
infection treated by antibiotics.
AB - : We report the case of a 69 years old man with left hip prosthesis, who
presented clinical, biochemical and imaging signs of periprosthetic infection
treated with linezolid, an antibacterial agent of the oxazolidinone class. Two
weeks after this treatment, a fluorine-18-fluoro-2-deoxy-d-glucose positron
emission tomography/computed tomography (18F-FDG PET/CT) scan showed increased
uptake in the skeleton and also increased uptake in several focal areas in the
spine and near the prosthesis and the surgical wound on the left gluteus medius.
Bone marrow biopsy was negative; meanwhile the antibiotic therapy, after four
weeks of treatment was stopped due to red blood cells and platelets toxicity. Six
weeks later, the patient developed high fever again and in order to revaluate the
periprosthetic inflammation, he was resubmitted to 18F-FDG PET/CT which showed
normal 18F-FDG uptake in the whole skeleton, including the prosthesis and the
subcutaneous wound. Some focal areas of increased uptake in the lumbar spine were
still detected. In the next 4 weeks the patient was under a "watch and wait"
follow-up in a steady state. IN CONCLUSION: In the case we report, since we found
no otnt focal areas in the lumbar spine where due to age-related bone deformities
including some Schmorl's nodes. The inflammation in the bone prosthesis and the
subcutaneous wound responded almost totally to the antibiotic treatment we
applied.
PMID- 28697198
TI - Unusual diffuse liver 18F-FDG uptake in melanoma patient treated by ipilimumab.
AB - We present herein a case of unusual 18F-FDG PET-CT diffuse hypermetabolic liver
uptake in melanoma patient treated by ipilimumab.
PMID- 28697199
TI - Negative 18F-FDG PET and positive CT and MRI findings in multifocal splenic
hamartoma.
AB - : We report our fluorine-18-fluorodeoxyglucose positron emission
tomography/computed tomography (18FFDG PET/CT) findings in a 51 years old female
presenting with B symptoms, respectively fever, night sweats and malaise, that
underwent an 18F-FDG PET/CT examination to exclude underlying lymphomatous
disease. Whereas 18F-FDG PET scan findings were negative, CT put to evidence the
presence of multiple small lesions suggestive for multifocal hamartoma. On a
subsequently performed magnetic resonance imaging (MRI) of the spleen, multiple
infracentimetric foci were visualized displaying characteristic findings for
hamartoma. During a follow-up period of two years no change in size or
characteristics of these lesions occurred. CONCLUSION: The normal :F-FDG PET/CT
findings suggested that, at least in this patient, splenic hamartoma may display
a similar :F-FDG avidity when compared to normal splenic tissue. Alternatively,
due to the infra-centrimeric size of the hamartoma and spill-over from :F-FDG
activity from neighbouring normal tissue, the true 18F-FDG avidity of the
hamartomas present might also be overestimated.
PMID- 28697200
TI - Economic Evaluation of Implant-Supported Overdentures in Edentulous Patients: A
Systematic Review.
AB - PURPOSE: Edentulous patients benefit significantly from implant-supported
overdenture prostheses. The purpose of this systematic review was to evaluate the
cost-effectiveness of implant-supported overdentures (IODs) for edentulous
patients. MATERIALS AND METHODS: The search was limited to studies written in
English and included an electronic and manual search through MEDLINE (Ovid, 1946
to November 2015), Embase (Ovid, 1966 to November 2015), Cochrane Central
Register of Controlled Trials (CENTRAL) (to November 2015), and PubMed (to
November 2015). Two investigators extracted the data and assessed the studies
independently. No meta-analysis was conducted due to the high heterogeneity
within the literature. RESULTS: Of the initial 583 selected articles, 10 studies
involving 802 participants were included. Of these, 6 studies had a high risk of
bias and the rest had an unclear risk of bias. Implant-supported prostheses were
more cost-effective when compared to conventional dentures and fixed implant
supported prostheses. Overdentures supported by two implants and magnet
attachment were reported as cost-effective. CONCLUSION: Implant-supported
overdentures are a cost-effective treatment for edentulous patients. More
clinical studies with appropriate scientific vigor are required to further assess
the cost-effectiveness of implant-supported overdentures.
PMID- 28697201
TI - Ability of General Dentists and Prosthodontists to Discern and Identify
Incremental Increases in Occlusal Vertical Dimension in Dentate Subjects.
AB - PURPOSE: The aim of this study was to determine whether dentists are able to
discern and identify increases in occlusal vertical dimension (OVD) in dentate
subjects without apparent loss of OVD. MATERIALS AND METHODS: A total of 10
dentate subjects had mandibular overlays fabricated at 2-, 3-, 4-, and 5-mm
openings of the anterior guide pin (AGP) of a semiadjustable articulator.
Standardized frontal and profile photographs with subjects wearing each of the
overlays were made. Photographs were presented in random order to 40 judges
comprising 20 prosthodontists and 20 general dentists who were informed about the
purpose of the study. Judges first rated the degree of facial naturalness on a
visual analog scale (VAS) and then took a discriminatory sensory analysis test
(triangle test) where they were required to correctly identify the image with no
increase in OVD from a set of three images. RESULTS: Mean VAS ratings for facial
naturalness were inversely correlated with incremental increases in OVD,
irrespective of the judge's background. Though subjects were rated less natural
with incremental increases in OVD, only a 5-mm increase from baseline was
clinically significant (P < .05). For the triangle test, judges correctly
identified the image with a 3-mm increase in OVD 57% of the time (P < .582),
irrespective of the judge's profession, sex, race, and years in practice, which
were clinically insignificant. CONCLUSION: Increasing OVD by a 5-mm opening of
the AGP of the articulator significantly decreased the judge's evaluation of
facial naturalness. The ratings were more pronounced in female subjects than in
male subjects. However, an increase in OVD of 3 mm was visually indistinguishable
by the judges.
PMID- 28697202
TI - A Randomized Crossover Trial Comparing Patient Preference for Mandibular Complete
Dentures Made with Two Different Techniques: A Short-Term Follow-Up.
AB - PURPOSE: The objective of this trial was to compare short-term patient preference
for two mandibular complete denture (CD) fabrication techniques: neutral zone
(NZ) and conventional (CV). MATERIALS AND METHODS: A prospective, within-subject,
randomized crossover trial was performed on a sample of 37 edentulous patients
with complete denture experience. Two new sets of CDs were made for each patient,
one set with a CV and one with a NZ mandibular denture. After consecutively
wearing each set for at least 2 months after the last adjustment visit, patients
indicated their preference (CV, NZ, or none). Associations and comparisons were
made using the generalized linear model (GLM) and Fisher exact test between
preference and sex, age, period of edentulousness, tissue quality, prosthodontic
diagnostic index (PDI), and oral health-related quality of life (OHRQoL)
differences of the two interventions assessed using the 20-item oral health
impact profile (OHIP-20). Significance was determined at P = .05. RESULTS: A
total of 15 (40%) patients preferred NZ, 8 (22%) preferred CV dentures, and 14
(38%) had no preference. Although more women preferred NZ over CV dentures (50%
versus 27%), difference in preference according to sex was not significant (P =
.359). Neither was difference in preference and PDI scores significant (P =
.603). Preference could not be strongly associated to period of edentulousness,
age, tissue scores, and differences in OHIP-20 scores (P > .05), except for OHIP
20 scores and NZ preference (P < .001). Better fit, comfort, and eating were
reasons patients preferred a type of denture. These reasons were identified for
both types of denture. Appearance and speech were not identified as reasons for a
particular preference. CONCLUSION: Based on preference expressed by patients,
there is no difference between NZ and CV mandibular dentures. Denture preference
could not be related to patient variables over the study's time frame.
PMID- 28697203
TI - Does Surgical Experience Influence Implant Survival Rate? A Systematic Review and
Meta-Analysis.
AB - PURPOSE: The aim of this study was to assess the evidence of a correlation
between the expertise of surgeons and the survival rate of dental implants.
MATERIALS AND METHODS: An electronic search in four databases (MEDLINE, EMBASE,
SCOPUS, and the Cochrane Library) was performed for publications from their
inception to May 2016 and was supplemented by manual searches. Prospective and
retrospective cohorts were included if they met the following criteria: (1) the
presence of an exposed group (inexperienced surgeons); and (2) the presence of a
control group (experienced surgeons). Meta-analyses were performed to evaluate
the effect of expertise on implant failure. RESULTS: Of 609 potentially eligible
articles, 8 were included in the qualitative analysis and 6 in the quantitative
synthesis. Two meta-analyses were performed for different definitions of
experienced surgeons. In the first meta-analysis, which included four
retrospective comparative studies that defined experienced professionals as
specialists, the experience of the surgeon did not significantly affect the
implant failure rate (P = .54), with an odds ratio (OR) of 1.24 (95% CI, 0.62
2.48). In the second meta-analysis, which included two retrospective studies that
defined experienced surgeons as professionals that had placed more than 50
implants, the expertise of the surgeon did significantly affect the implant
failure rates (P = .0005), with an OR of 2.18 (95% CI, 1.40-3.39). CONCLUSION:
The data from the included publications suggest that surgical experience did not
significantly affect implant failure when considering experience based on
specialty but were significantly affected when considering experience based on
the number of implants placed. Further standardized prospective studies with a
control of confounding factors are needed to clarify the role of surgical
expertise on implant survival rates.
PMID- 28697204
TI - Preliminary Clinical Application of Removable Partial Denture Frameworks
Fabricated Using Computer-Aided Design and Rapid Prototyping Techniques.
AB - PURPOSE: The aim of this study was to explore the application of computer-aided
design and rapid prototyping (CAD/RP) for removable partial denture (RPD)
frameworks and evaluate the fitness of the technique for clinical application.
MATERIALS AND METHODS: Three-dimensional (3D) images of dentition defects were
obtained using a lab scanner. The RPD frameworks were designed using commercial
dental software and manufactured using selective laser melting (SLM). A total of
15 cases of RPD prostheses were selected, wherein each patient received two types
of RPD frameworks, prepared by CAD/RP and investment casting. Primary evaluation
of the CAD/RP framework was performed by visual inspection. The gap between the
occlusal rest and the relevant rest seat was then replaced using silicone, and
the specimens were observed and measured. Paired t test was used to compare the
average thickness and distributed thickness between the CAD/RP and investment
casting frameworks. Analysis of variance test was used to compare the difference
in thickness among different zones. RESULTS: The RPD framework was designed and
directly manufactured using the SLM technique. CAD/RP frameworks may meet the
clinical requirements with satisfactory retention and stability and no undesired
rotation. Although the average gap between the occlusal rest and the
corresponding rest seat of the CAD/RP frameworks was slightly larger than that of
the investment casting frameworks (P < .05), it was acceptable for clinical
application. CONCLUSION: RPD frameworks can be designed and fabricated directly
using digital techniques with acceptable results in clinical application.
PMID- 28697205
TI - Different Patterns of Restoration Provision Between Initial Endodontic Treatment
and Retreatment: A Retrospective Clinical Study.
AB - PURPOSE: The aim of this study was to investigate the relationship between type
of endodontic treatment and choice of definitive restoration and to show the
prevalence of endodontic treatment options according to patient age and type of
tooth. MATERIALS AND METHODS: Data were collected from the archive system of the
School of Dentistry, National and Kapodistrian University of Athens in Athens,
Greece. The sample included endodontically treated teeth being restored
definitively at the time of data collection. RESULTS: Statistically significant
difference was found regarding the type of restoration between initial endodontic
treatments and retreatments (P < .001). CONCLUSION: Endodontic retreatment seemed
to have a significant effect on the choice of definitive restoration of the
tooth.
PMID- 28697206
TI - An Overview of Systematic Reviews Related to Aspects of the Shortened Dental Arch
and Its Variants in Adults.
AB - PURPOSE: The aim of this study was to conduct an overview of systematic reviews
(SRs) related to aspects of the shortened dental arch (SDA) and its variants and
critically appraise the methodologic quality of included SRs using the AMSTAR
checklist. MATERIALS AND METHODS: A comprehensive computerized search and a hand
search of reference lists were conducted for SRs related to SDAs to identify
publications from 2000 to 2016. All the present authors and a research assistant
independently screened the results of the electronic searches using an
eligibility form and extracted information using a specially designed prepiloted
data extraction form. An 11-question AMSTAR checklist was completed for each
included SR. Disputes were resolved by discussion between all researchers, and
results were collated and interpreted. RESULTS: For the period of 2007 to 2016,
the search yielded nine SRs incorporating 228 related articles. The research
questions for each SR differed but were related to SDAs, thus, the included
articles were similar across SRs. Characteristics such as aims/objectives, study
outcomes, and conclusions of the nine included SRs were compared. The AMSTAR
evaluation indicated that five out of nine studies were of a high quality (used a
rigorous methodology) and the remaining four were of medium quality. All nine SRs
provided designs and characteristics of included studies. None of the SRs
assessed publication bias. CONCLUSION: Of the nine SRs, seven drew positive
conclusions regarding the SDA concept, finding it functionally sound, although
some suggested that more high-quality primary studies are still needed. The
AMSTAR calculation indicated that most included SRs had an acceptable
methodologic quality, emphasizing the reliability of their results.
PMID- 28697207
TI - Reliability of a CAD/CAM Surgical Guide for Implant Placement: An In Vitro
Comparison of Surgeons' Experience Levels and Implant Sites.
AB - PURPOSE: This in vitro study evaluated the reliability of a surgical guide with
regard to different levels of operator surgical experience and implant site.
MATERIALS AND METHODS: A stereolithographic surgical guide for epoxy resin
mandibles with three edentulous molar sites was produced using a computer-aided
design/computer-assisted manufacture (CAD/CAM) system. Two surgeons with and two
surgeons without implant surgery experience placed implants in a model either
using or not using the CAD/CAM surgical guide. Four groups were created:
inexperienced surgeon without the guide (group 1); experienced surgeon without
the guide (group 2); inexperienced surgeon with the guide (group 3); and
experienced surgeon with the guide (group 4). Planned implants and placed
implants were superimposed using digital software, and deviation parameters were
calculated. RESULTS: There were no significant differences in any of the
deviation parameters between the groups when using the surgical guide. With
respect to the implant sites, there were no significant differences among the
groups in any parameter. CONCLUSION: Use of the CAD/CAM surgical guide reduced
discrepancies among operators performing implant surgery regardless of their
level of experience. Whether or not the guide was used, differences in the
anterior-posterior implant site in the molar area did not affect the accuracy of
implant placement.
PMID- 28697208
TI - Osseointegration of a Zirconia Implant: A Histologic Assessment.
AB - PURPOSE: The aim of this study was to describe the histologic and
histomorphometric features of a retrieved, functional endosseous zirconia implant
in a human subject. MATERIALS AND METHODS: A maxillary zirconia implant (ZV3)
placed in a 52-year-old man was retrieved after 2 years of uncompromised service
and prepared for light microscopic evaluation. RESULTS: Histologic examination
demonstrated good osseointegration. Bone contact measurements revealed a mean
percentage of bone-to-implant contact of 55.8% (SD 3.8%). CONCLUSION: The
histologic data provide further evidence of the potential of zirconia implants to
osseointegrate to a similar degree as titanium in humans.
PMID- 28697209
TI - Improvement of a Digital Impression with Conventional Materials: Overcoming
Intraoral Scanner Limitations.
AB - Intraoral digital impression is a viable alternative to conventional impression
techniques and has been proven to be even more accurate than conventional
materials. Nevertheless, there are cases in which the rheologic properties of
conventional materials can be helpful. This article describes a method to
overcome an insufficient sulcus-depth reading of intraoral scanners in
challenging cases.
PMID- 28697210
TI - Reproducibility of a New Computerized Planimetric Method for the Measurement and
Assessment of Removable Dental Prostheses Plaque.
AB - PURPOSE: The aim of this study was to evaluate the reliability and agreement of a
new computerized planimetric method (CPM) for the measurement and assessment of
plaque on all types of removable dental prostheses (RDPs). MATERIALS AND METHODS:
From a database containing 780 images taken following a standardized method for
65 RDPs, 55 images were randomly selected for image analysis. Adobe Photoshop
software was used according to standard operating procedure (SOP) by one main
examiner two times in different sessions, and one time by three additional
examiners. To estimate the intra- and interexaminer reliability, intraclass
correlation coefficient ICC(2,1) were used. Three parameters were used to
estimate agreement: standard error of measurement (SEM), smallest detectable
change at the 95% confidence level (SDC95%), and limits of agreement (LoA)
according to the Bland-Altman method. RESULTS: In all steps of the image
analysis, both intra- and interexaminer reliability were excellent, with ICC(2,1)
values > 0.85 at the 95% confidence level. The intra- and interexaminer values
for both the SEMagreement and SDC95% were <= 6% and <= 17%, respectively. The
Bland-Altman analysis revealed a satisfactory level of agreement. CONCLUSION:
This study shows excellent inter- and intraexaminer reproducibility, a
satisfactory level of examiner agreement, and acceptable measurement error.
Furthermore, the method can be used with all types of RDPs. The CPM is more
suitable for clinical research because of its objectivity, reliability, high
level of standardization, and ability to detect and quantify small changes in
plaque.
PMID- 28697211
TI - Comparison of Clinical, Radiographic, and Immunologic Inflammatory Parameters
Around Dental Implants with Cement-Retained and Screw-Retained Restorations: A 5
Year Prospective Cohort Study in Men.
AB - PURPOSE: To compare bleeding on probing (BoP), probing depth (PD; >= 4 mm),
radiographic (peri-implant crestal bone loss [CBL]), and immunologic inflammatory
(interleukin-1beta [IL-1beta] and matrix metalloproteinase-9 [MMP-9]) parameters
around dental implants with cement-retained (CR) and screw-retained (SR) implant
supported crowns. MATERIALS AND METHODS: Based on the mode of retention of the
restoration, 51 patients were divided into two groups: Group 1, consisting of 26
single implants restored with CR crowns, and Group 2, consisting of 25 single
implants restored with SR crowns. Peri-implant BoP, PD, and CBL were scored, and
levels of IL-1beta and MMP-9 in the peri-implant crevicular fluid (PICF) in both
groups were measured in duplicate using enzyme-linked immunosorbent assay. Full
mouth mechanical debridement was performed biannually in both groups. Statistical
analysis was performed using Kruskal-Wallis test with the significance level set
at P < .05. RESULTS: The mean CBL among implants in groups 1 and 2 was 1.7 +/-
0.5 mm and 1.7 +/- 0.4 mm, respectively. There was no statistically significant
difference in mean BoP, PD, and CBL among implants in both groups (P > .05).
There was no statistically significant difference between groups 1 and 2 in the
PICF levels of IL-1beta (7.3 +/- 0.5 and 7.2 +/- 0.5, respectively) and MMP-9
(165 +/- 9.4 and 182 +/- 10.6, respectively) (P > .05). CONCLUSION: The mode of
retention of implant-supported crowns does not appear to affect their clinical
correlations with BoP, PD, CBL, and levels of IL-1beta and MMP-9 in the PICF when
zinc oxide eugenol cement is used.
PMID- 28697212
TI - Maxillary Implant Prosthodontic Treatment Using Digital Laboratory Protocol for a
Patient with Epidermolysis Bullosa: A Case History Report.
AB - Epidermolysis bullosa belongs to a group of genetic diseases that present with
skin disorders and is characterized by generalized blister formation in response
to mechanical trauma. This article reports on the management of a recessive
dystrophic epidermolytic patient with four remaining periodontally compromised
maxillary teeth. Treatment involved placement of four maxillary implants and use
of computer-aided design/computer-assisted manufacture techniques to fabricate a
fixed full-arch implant-supported prosthesis. The prescribed dental treatment
protocol led to a successful short-term prosthodontic outcome.
PMID- 28697213
TI - Mega-abrasion: Case History Report on Management of a Fluorosis-Affected Patient.
AB - Different approaches ranging from veneers and crowns to employing the more
conservative use of freehand resin composites have been proposed to correct
esthetic problems caused by enamel fluorosis (EF). However, the protocol of mega
abrasion followed by microabrasion may be used as an alternative. It is less
invasive and can minimize the unesthetic brown-to-whitish spots caused by EF.
This article describes an easy and low-cost technique for managing enamel defects
in a patient with severe enamel fluorosis.
PMID- 28697214
TI - Facilitation of Prosthetic Rehabilitation in Scleroderma: Case History Report.
AB - Dental management of scleroderma patients is difficult and complicated because of
compromised intraoral access. Physiotherapy may play an adjunctive and effective
treatment role as described in a follow-up report on a previously documented case
history.
PMID- 28697215
TI - Update on the Systemic Risks of Superpotent Topical Steroids.
AB - INTRODUCTION: The potential for systemic effects due to percutaneous
absorption of superpotent topical steroids has been a longstanding concern. The
Food and Drug Administration currently recommends limiting the use of superpotent
topical steroids to 50g per week for 2 or 4 consecutive weeks depending on the
formulation, which is mostly based on the exact duration with which phase 3
clinical trials were allowed to be conducted per the FDA. This article reviews
all published clinical incidence of adrenal adverse effects in the medical
literature, specifically Cushing's syndrome (CS) and pathologic adrenal
suppression (PAAS), to try to ascertain a more realistic limit for the safe use
of superpotent topical steroids as it pertains to its potential systemic
effects.
METHODS: Literature search was conducted using PubMed. Only cases
of CS and PAAS secondary to the use of Class I superpotent topical steroids were
included. Pediatric cases and full articles unavailable in English were
excluded.
RESULTS: There were a total of 14 cases of CS and 5 cases of
subsequent PAAS found in the current literature.
DISCUSSION: From our
review of these cases, if the amount used per week is within FDA guidelines, it
appears that patients needed to use superpotent topical steroids for far greater
than 2 or 4 weeks to develop CS or PAAS. CS did not necessarily predict
occurrence of PAAS, but in all cases CS appeared to be a prerequisite for
developing PAAS. All cases of CS and all but one case of PAAS were reversible. If
excessive amount of greater than 50g per week is avoided, it appears that
superpotent topical steroids may be safe to use consecutively for months, perhaps
even years, without causing systemic effects.
J Drugs Dermatol.
2017;16(7):643-648.
.
PMID- 28697216
TI - Drivers of Healthcare Costs Among the Costliest Patients With Psoriasis Over
Three Years in a United States Health Plan.
AB - OBJECTIVE: To compare patients with psoriasis by cost level over 3 years.
METHODS: Psoriasis patients in a large US health plan in 2011-2013 were
identified. Four groups were created by healthcare costs excluding biologics:
patients having top 10% of costs in all 3 years (Top), top 10% in 2 of 3 years
(High), bottom 90% in 2 of 3 years (Medium), and bottom 90% in all 3 years
(Bottom). Comorbidities, utilization, and costs between groups were compared.
RESULTS: The study included 18,653 patients: 514 (3%), 805 (4%), 2,443 (13%),
and 14,891 (80%) patients in the Top, High, Medium, and Bottom groups,
respectively. Significantly more patients in the Top vs Bottom group had diabetes
(31.1% vs 9.4%), cardiovascular disease (26.5% vs 4.3%), psoriatic arthritis
(25.7% vs 10.7%), depression (27.8% vs 6.9%), and anxiety (22.0% vs 7.9%) in 2011
(all P less than 0.05). Patients in the Top group had more unique 2011
prescriptions (17.7 vs 6.6; P less than 0.001) than the Bottom group, but similar
biologic use (22.4% vs 21.6%). Patients in the Top, High, Medium, and Bottom
groups had mean 2011 total costs of $68,913, $40,575, $24,292, and $8,815, and
contributed to 14%, 13%, 23%, and 51% of the overall costs, respectively. Mean
total costs increased 14-18% over time for all groups. Although mean 2011 total
costs for patients in the Top group were 7.8 times of those in the Bottom group,
psoriasis-related costs were less disparate ($8,716 vs $4,541). Compared with
patients in the Bottom group, those in the Top group were more likely to have any
2011 hospitalization (36.8% vs 2.6%; psoriasis-related: 11.1% vs 0.7%) or
emergency visit (50.8% vs 20.8%; psoriasis-related: 3.9% vs 1.0%).
CONCLUSION: The costliest patients with psoriasis had significantly higher
prevalence of comorbidities, prescription fills, inpatient and emergency
utilization, but not biologic medication use or biologic costs.
J
Drugs Dermatol. 2017;16(7):651-658.
.
PMID- 28697217
TI - Expert Consensus on Absorbable Advanced Suspension Technology for Facial Tissue
Repositioning and Volume Enhancement.
AB - BACKGROUND: Signs of facial aging include wrinkles, loss of subcutaneous
volume, decreased tone, texture, and sagging of the skin. The objective of this
review is to determine whether facial suspension absorbable sutures are a safe
and effective modality for facial rejuvenation.
METHOD: A group of US
plastic surgeons and dermatologists who practice medical aesthetics convened to
review evidence obtained from literature searches and to reach a consensus on
clinical practice guidelines for the use of facial absorbable suspension
sutures.
RESULTS: Currently, there are different types of lifting sutures
available. Absorbable, facial suspension sutures allow for superior repositioning
of tissue along a vector line together with the added benefit of volumization of
the area. These benefits are for patients who have moderate facial aging and
require treatment beyond the use of injectable products only.
CONCLUSIONS:
Treatment with absorbable facial suspension sutures, when performed properly, is
associated with minor and infrequent complications and offers a beneficial
clinical alternative to traditional facial rejuvenation techniques.
J
Drugs Dermatol. 2017;16(7):661-666.
.
PMID- 28697218
TI - A 1% Colloidal Oatmeal Cream Alone is Effective in Reducing Symptoms of Mild to
Moderate Atopic Dermatitis: Results from Two Clinical Studies.
AB - BACKGROUND: The epidermal barrier in patients with atopic dermatitis (AD) is
deficient in ceramides and cathelicidins. Such epidermal defects may be a trigger
for AD, thereby encouraging research toward development of skin-barrier-targeted
preventive strategies.
METHODS: Two single-center, single-arm clinical
trials were conducted (study 1, age greater than equal to 8 years and study 2,
greater than equal to 10 years) in patients with mild to moderate AD to evaluate
the effects of an over-the-counter 1% colloidal oatmeal cream administered for 14
days. Study 1 assessed the Eczema Area and Severity Index (EASI) and
Investigator's Global Atopic Dermatitis Assessment (IGADA) on day 3, and itch
severity using a Visual Analogue Scale (VAS) immediately after application as
primary efficacy endpoints. In study 2, the primary efficacy endpoint was change
from baseline in patients' assessment of itch. Both studies assessed safety
through adverse event (AE) recording.
RESULTS: Study 1: 29 patients were
enrolled (mean age [range], 27.07 [8 -67]). Comparing to baseline, EASI, IGADA,
and itch were improved after the application, and improvements were maintained
until day 14. Improvements of greater than/equal to 20% over baseline were noted
in 53.6% and 25.0% patients at day 3 for EASI and IGADA scores, respectively, and
in 37.9% patients for itch score immediately after the product application. On
day 14, these percentages were 82.8%, 62.1%, and 85.7%, respectively.
STUDY 2: 30 patients were enrolled (mean age [range], 32.9 [10-80]). Itch
severity and EASI score were significantly improved after product application and
improvements were maintained until day 14. Transepidermal water loss values were
significantly reduced and skin hydration was significantly increased at all
assessment time points. No adverse events (AEs) were reported in study 2 and 2
AEs were reported by 1 patient in study 1.
CONCLUSIONS: The colloidal
oatmeal cream was well tolerated and clinically effective in patients with mild
to moderate AD.
J Drugs Dermatol. 2017;16(7):671-676.
.
PMID- 28697219
TI - The Role of a Natural Mollusk Egg-Derived Ingredient in Facial Appearance.
AB - New cosmeceutical ingredients that improve skin appearance are of interest to
the dermatologist. Cryptomphalus aspersa is a snail raised on farms in Spain for
its mucinous secretions and eggs. These natural products have been demonstrated
in vitro to trigger mesenchymal stem cell differentiation, promote dermal
fibroblast and keratinocyte migration, prevent keratinocyte aging, prevent
oxidative damage, stimulate the extracellular matrix, and regulate MMPs. This 12
week study enrolled 40 male and female subjects age 40-70 years of Fitzpatrick
skin types I-IV with moderate to severe facial aging and Rao-Goldman scores of 4
5 who applied an eye and face anti-aging cream twice daily containing a mollusk
egg extract. Dermatologist investigator, subject, and elasticity assessments were
performed at baseline, week 8, and week 12. At week 12, the investigator rated a
53% reduction in skin roughness (P less than 0.001), 26% improvement in skin
brightness (P less than 0.001), and 12% reduction in skin dyspigmentation
(P=0.033). The noninvasive elastometer measurements demonstrated an increase in
skin elasticity at week 8 of 11% with a continuing elasticity increase at week 12
of 39% (P less than 0.001). The formulation studied included moisturizing,
emollient, film-forming, and retinoid ingredients in addition to the mollusk egg
extract to produce the clinical improvement.
J Drugs Dermatol.
2017;16(7):678-681.
.
PMID- 28697220
TI - Orf Virus Infection in Humans: A Review With a Focus on Advances in Diagnosis and
Treatment.
AB - Ecthyma contagiosum, also called contagious pustular dermatosis, is a zoonotic
disease caused by the orf virus (OrfV). As a member of the poxviridae family and
parapoxvirus genus, this dermatotropic virus has developed an array of mechanisms
by which to evade the host immune system in both humans and animals. The
ubiquitousness of this pathogen in sheep, goats, and deer has led to the
development of orf in diverse areas around the world. Human disease occurs via
direct contact with infected animals or fomites. Rarely, human-to-human
transmission has been reported. The disease progresses through six clinically
distinct dermatologic stages and lesions usually heal in three to six weeks
without scarring. Farmers, veterinarians, and hunters represent high-risk groups,
as their repeated contact with livestock and wild animals predisposes them to
infection. With an increasing number of cattle, livestock, and wild animals being
kept as pets, human orf may become more prevalent in the future. Taken with the
lack of a widely accepted and successful antiviral treatment regimen, this
demonstrates the importance of conducting additional research to further
elucidate the pathogenic effects of the OrfV in humans. J Drugs Dermatol.
2017;16(7):684-689.
PMID- 28697221
TI - Hair Loss Myths.
AB - INTRODUCTION: Hair loss is a common complaint seen in dermatology clinics.
From frustration and attempts at self-help, patients with hair loss may present
to the dermatologist with false beliefs, or myths, about the causes of their
condition and what treatments are effective.
METHODS: We identified 12
common myths about hair loss, categorized as myths about minoxidil treatment,
vitamin and mineral supplements, natural topical treatments, and hair care
practices. We performed a PubMed search to find evidence to support or refute
each myth.
RESULTS: We found that there is little evidence to support many
of these common hair loss myths. In some cases, randomized controlled trials have
investigated the effects of particular therapies and point to the effectiveness
of certain hair loss treatments.
DISCUSSION: In many cases, there have not
been sufficient randomized controlled trials to evaluate the effect of different
therapies and hair care practices on hair loss. It is best to guide patients
toward treatments with a long track record of efficacy and away from those where
little is known scientifically.
J Drugs Dermatol. 2017;16(7):690
694.
.
PMID- 28697222
TI - Injection Site Reactions to Biologic Agents Used in Psoriasis and Psoriatic
Arthritis.
AB - Psoriasis is a chronic inflammatory cutaneous disease that affects 2-3% of the
general population. Up to 30% of patients with psoriasis also develop psoriatic
arthritis, a chronic inflammatory and progressive arthritis. Although their
precise pathogeneses remain unclear, psoriasis and psoriatic arthritis involve
altered expression of proinflammatory cytokines, including tumor necrosis factor
alpha, interleukin (IL)-12, IL-17, IL-22, and IL-23. The development of biologic
agents that target these cytokines has greatly improved the treatment of
psoriatic disease. Injection site reactions have been reported with many of these
therapies. In this paper, we will present cases and review the literature on
injection site reactions with the major biologic agents administered
subcutaneously for the treatment of psoriasis and psoriatic arthritis.
J Drugs Dermatol. 2017;16(7):695-698.
.
PMID- 28697223
TI - Treatment of Annular Elastolytic Giant Cell Granuloma With Topical Tretinoin.
AB - Annular elastolytic giant cell granuloma, also known as actinic granuloma, is
a rare skin condition with a chronic course that is often resistant to treatment.
Literature is sparse, and only a handful of case reports are available to guide
treatment decisions. Typical first line treatment options include topical and
intralesional steroids, topical pimecrolimus, and cryotherapy. Resistant cases
have been treated with cyclosporine, systemic steroids, antimalarials, and oral
retinoids. In particular, acitretin and isotretinoin have shown success in three
cases. However, these medications can have side effects and require frequent lab
monitoring. We present a case of a 47-year-old woman with bilateral forearm
lesions consistent with annular elastolytic giant cell granuloma who was
successfully treated with topical tretinoin.
J Drugs Dermatol.
2017;16(7):699-700.
.
PMID- 28697224
TI - Acquired Epidermodysplasia Verruciformis and Its Relationship to
Immunosuppressive Therapy: Report of a Case and Review of the Literature.
AB - INTRODUCTION: Epidermodysplasia verruciformis (EV) is a rare inherited dermatosis
characterized by increased susceptibility to human papilloma virus infection.
Acquired EV occurs in patients with compromised cell-mediated immunity, such as
patients with HIV and transplant recipients. Optimal management of acquired EV
has not yet been established, as cases are rare and are due to a variety of
underlying conditions. Additionally, no distinctions have been made between
different immunosuppressive medications and their respective link to EV. METHODS
AND RESULTS: We report a patient with systemic lupus erythematosus who developed
EV while on azathioprine and prednisone. The patient's lesions resolved
completely after she was switched from azathioprine to mycophenolate mofetil. Her
lesions recurred when her immunosuppressive regimen was again changed from
mycophenolate mofetil to methotrexate. A review of the literature revealed
azathioprine to be related to other cases of acquired EV. DISCUSSION: This case
indicates a possible link between specific immunosuppressive drugs and the
development of EV, allowing for new EV treatment considerations. In this case and
previous cases, azathioprine is indicated as being particularly linked with the
development of EV, while mycophenolate mofetil may be an immunosuppressive option
that is less likely to induce EV in patients predisposed to this condition. J
Drugs Dermatol. 2017;16(7):701-704.
PMID- 28697225
TI - Low-dose Methotrexate for Vitiligo.
AB - BACKGROUND: Treatment of vitiligo is aimed at repigmentation and often
consists of multiple modalities, none of which are universally or rapidly
successful. Extensive cases are most often treated with ultraviolet light
therapy, which can be both costly and time-consuming. Though vitiligo is an
autoimmune disease, there is no current data to support systemic
immunosuppressive monotherapy.
CASE SUMMARY: Here we present a case series
of 3 patients with vitiligo treated for 11-16 months with low-dose methotrexate
(12.5-25 mg per week) with folic acid supplementation with clinically significant
skin repigmentation, with response within 6 months in one case. There were no
severe adverse effects reported.
CONCLUSION: These cases demonstrate an
unexplored effective and steroid-sparing therapeutic alternative in patients with
vitiligo for whom topical therapy has failed and phototherapy is cost-prohibitive
or ineffective.
J Drugs Dermatol. 2017;16(7):705-706.
.
PMID- 28697226
TI - Randomized, Split-Face/Decollete Comparative Trial of Procedure Enhancement
System for Fractional non-Ablative Laser Resurfacing Treatment.
AB - INTRODUCTION: A topical proprietary procedural enhancement system (PES)
containing a combination of active ingredients including a tripeptide and
hexapeptide (TriHex TechnologyTM, Alastin Procedure Enhancement Invasive System,
ALASTIN SkincareTM, Inc., Carlsbad, CA) has been used successfully to aid in
healing and improve symptomatology following resurfacing procedures.
METHODS: PES (Gentle Cleanser, Regenerating Skin Nectar with TriHex
TechnologyTM, Ultra Nourishing Moisturizer with TriHex TechnologyTM, Soothe +
Protect Recovery Balm, Broad Spectrum 30+ Sunscreen) was compared to a basic
regimen (AquaphorTM, CeraveTM cleanser, VanicreamTM, Alastin Broad Spectrum 30+
Sunscreen) in a split face/ decollete trial following fractional non-ablative
thulium-doped resurfacing treatment to the face or decollete. The skin was pre
conditioned and treated during and after the procedure using the two
regimens.
RESULTS: A blinded investigator rated the PES statistically
superior to the basic regimen on healing post-laser treatment on day 4 based on
lentigines, texture, and Global Skin Quality. Subjects also reported 'better
looking and feeling' skin on the PES side.
CONCLUSION: PES appears to
improve healing post-non ablative thulium-doped resurfacing treatment to the
face/decollete in comparison with standard of care.
J Drugs Dermatol.
2017;16(7):707-710.
.
PMID- 28697227
TI - Postoperative Pyoderma Gangrenosum Following Video-Assisted Thoracic Surgery.
AB - Pyoderma gangrenosum (PG) is a neutrophilic, ulcerative dermatosis that can
develop at sites of cutaneous trauma, including surgical incisions, a phenomenon
known as pathergy. The characteristic lesion is a painful, rapidly expanding
ulceration with a violaceous undermined border.1 A biopsy taken from
the expanding violaceous border shows predominantly neutrophilic dermal
inflammation with neutrophilic abscess formation.
The etiology of PG
appears to be variable among patients, as about a half of the reported cases are
associated with systemic disease such as inflammatory bowel disease, rheumatoid
arthritis, or myeloproliferative disorders, while the other half seem to be
idiopathic.2 PG is difficult to diagnose as other etiologies,
including infectious, vasculitic, and other inflammatory dermatoses, must be
excluded.1 Histopathologic and biochemical markers of PG, such as
dermal neutrophilic infiltrate or overexpression of interleukin-8,3
respectively, are not pathognomonic. Given that several drugs, such as
hydralazine, mesalamine, and sunitinib, are reportedly associated with PG,
failure to recognize this association and stop these medications may delay
diagnosis and therapy. We report a case of idiopathic postoperative PG following
video-assisted thoracic surgery (VATS).
J Drugs Dermatol.
2017;16(7):711-713.
.
PMID- 28697228
TI - Lichenoid Dermatitis From Interferon alpha-2a in a Patient With Metastatic Renal
Cell Carcinoma and Seronegative HCV.
AB - Cutaneous reactions to interferon, including a lichenoid drug reaction, are
most commonly reported in patients undergoing treatment for hepatitis C virus
(HCV) infection. There have been case reports of interferon-induced lichen planus
in seronegative HCV patients with lymphoproliferative disorders and melanoma. We
report the case of a 71-year-old man undergoing treatment with interferon for
metastatic renal cell carcinoma (RCC) who developed an eruption 2 months after
starting interferon. Clinical and histological findings from biopsies supported a
diagnosis of interferon-induced lichen planus. To our knowledge, this is the
first known case of a lichenoid drug eruption from interferon in a seronegative
HCV patient with metastatic RCC.
J Drugs Dermatol. 2017;16(7):714
716.
.
PMID- 28697229
TI - Healthful Diet and Physical Activity for Cardiovascular Disease Prevention in
Adults Without Known Risk Factors: Is Behavioral Counselling Necessary?
PMID- 28697230
TI - Healthful Physical Activity and Diet Promotion-For the Many or the Few?
PMID- 28697231
TI - Gadolinium/terbium hybrid macromolecular complexes for bimodal imaging of
atherothrombosis.
AB - We developed a fluorescence imaging microscope system intended for the
localization within artery slices of a gadolinium-based macromolecular
biospecific magnetic resonance (MR) contrast agent used for the visualization of
atherothrombosis. As the contrast agent is not initially fluorescent, we
substitute some gadolinium ions for terbium ions to make them fluorescent while
preserving their chemical characteristics. A long fluorescence emission time
constant enables us to have a suitable signal-to-noise ratio, despite a low
intensity, using pulsed illumination and time-gated imaging. Images of rat
arteries show that the contrast agent is indeed localized on the specific regions
of the tissues. We currently have a tool that allows us to understand and
optimize the MR contrast agent.
PMID- 28697232
TI - Photothermal strain imaging.
AB - Vulnerable plaques are the major cause of cardiovascular disease, but they are
difficult to detect with conventional intravascular imaging techniques.
Techniques are needed to identify plaque vulnerability based on the presence of
lipids in plaque. Thermal strain imaging (TSI) is an imaging technique based on
ultrasound (US) wave propagation speed, which varies with the medium temperature.
In TSI, the strain that occurs during tissue temperature change can be used for
lipid detection because it has a different tendency depending on the type of
tissue. Here, we demonstrate photothermal strain imaging (pTSI) using an
intravascular ultrasound catheter. pTSI is performed by slightly and selectively
heating lipid using a relatively inexpensive continuous laser source. We applied
a speckle-tracking algorithm to US B-mode images for strain calculations. As a
result, the strain produced in porcine fat was different from the strain produced
in water-bearing gelatin phantom, which made it possible to distinguish the two.
This suggests that pTSI could potentially be a way of differentiating lipids in
coronary artery.
PMID- 28697233
TI - Handheld optical coherence tomography-reflectance confocal microscopy probe for
detection of basal cell carcinoma and delineation of margins.
AB - We present a hand-held implementation and preliminary evaluation of a combined
optical coherence tomography (OCT) and reflectance confocal microscopy (RCM)
probe for detecting and delineating the margins of basal cell carcinomas (BCCs)
in human skin .24), and meta-regressions identified no associations of PAP with
outcomes for different levels of apnea severity, follow-up duration, or adherence
to PAP (all P values > .13). Conclusions and Relevance: The use of PAP, compared
with no treatment or sham, was not associated with reduced risks of
cardiovascular outcomes or death for patients with sleep apnea. Although there
are other benefits of treatment with PAP for sleep apnea, these findings do not
support treatment with PAP with a goal of prevention of these outcomes.
PMID- 28697255
TI - Counseling on Healthy Living to Prevent Cardiovascular Disease in Adults Without
Risk Factors.
PMID- 28697253
TI - Effect of Antidepressant Switching vs Augmentation on Remission Among Patients
With Major Depressive Disorder Unresponsive to Antidepressant Treatment: The VAST
D Randomized Clinical Trial.
AB - Importance: Less than one-third of patients with major depressive disorder (MDD)
achieve remission with their first antidepressant. Objective: To determine the
relative effectiveness and safety of 3 common alternate treatments for MDD.
Design, Setting, and Participants: From December 2012 to May 2015, 1522 patients
at 35 US Veterans Health Administration medical centers who were diagnosed with
nonpsychotic MDD, unresponsive to at least 1 antidepressant course meeting
minimal standards for treatment dose and duration, participated in the study.
Patients were randomly assigned (1:1:1) to 1 of 3 treatments and evaluated for up
to 36 weeks. Interventions: Switch to a different antidepressant, bupropion
(switch group, n = 511); augment current treatment with bupropion (augment
bupropion group, n = 506); or augment with an atypical antipsychotic,
aripiprazole (augment-aripiprazole group, n = 505) for 12 weeks (acute treatment
phase) and up to 36 weeks for longer-term follow-up (continuation phase). Main
Outcomes and Measures: The primary outcome was remission during the acute
treatment phase (16-item Quick Inventory of Depressive Symptomatology-Clinician
Rated [QIDS-C16] score <=5 at 2 consecutive visits). Secondary outcomes included
response (>=50% reduction in QIDS-C16 score or improvement on the Clinical Global
Impression Improvement scale), relapse, and adverse effects. Results: Among 1522
randomized patients (mean age, 54.4 years; men, 1296 [85.2%]), 1137 (74.7%)
completed the acute treatment phase. Remission rates at 12 weeks were 22.3% (n =
114) for the switch group, 26.9% (n = 136)for the augment-bupropion group, and
28.9% (n = 146) for the augment-aripiprazole group. The augment-aripiprazole
group exceeded the switch group in remission (relative risk [RR], 1.30 [95% CI,
1.05-1.60]; P = .02), but other remission comparisons were not significant.
Response was greater for the augment-aripiprazole group (74.3%) than for either
the switch group (62.4%; RR, 1.19 [95% CI, 1.09-1.29]) or the augment-bupropion
group (65.6%; RR, 1.13 [95% CI, 1.04-1.23]). No significant treatment differences
were observed for relapse. Anxiety was more frequent in the 2 bupropion groups
(24.3% in the switch group [n = 124] vs 16.6% in the augment-aripiprazole group
[n = 84]; and 22.5% in augment-bupropion group [n = 114]). Adverse effects more
frequent in the augment-aripiprazole group included somnolence, akathisia, and
weight gain. Conclusions and Relevance: Among a predominantly male population
with major depressive disorder unresponsive to antidepressant treatment,
augmentation with aripiprazole resulted in a statistically significant but only
modestly increased likelihood of remission during 12 weeks of treatment compared
with switching to bupropion monotherapy. Given the small effect size and adverse
effects associated with aripiprazole, further analysis including cost
effectiveness is needed to understand the net utility of this approach. Trial
Registration: clinicaltrials.gov Identifier: NCT01421342.
PMID- 28697254
TI - Association Between Alendronate Use and Hip Fracture Risk in Older Patients Using
Oral Prednisolone.
AB - Importance: Oral glucocorticoid treatment increases fracture risk, and evidence
is lacking regarding the efficacy of alendronate to protect against hip fracture
in older patients using glucocorticoids. Objective: To investigate whether
alendronate treatment in older patients using oral prednisolone is associated
with decreased hip fracture risk and adverse effects. Design, Setting, and
Participants: Retrospective cohort study using a national database (N = 433 195)
of patients aged 65 years or older undergoing a health evaluation (baseline) at
Swedish health care facilities; 1802 patients who were prescribed alendronate
after at least 3 months of oral prednisolone treatment (>=5 mg/d) were
identified. Propensity score matching was used to select 1802 patients without
alendronate use from 6076 patients taking prednisolone with the same dose and
treatment time criteria. Follow-up occurred between January 2008 and December
2014. Exposures: Alendronate vs no alendronate use; no patients had previously
taken alendronate at the time of prednisolone initiation. Main Outcomes and
Measures: The primary outcome was incident hip fracture. Results: Of the 3604
included patients, the mean age was 79.9 (SD, 7.5) years, and 2524 (70%) were
women. After a median follow-up of 1.32 years (interquartile range, 0.57-2.34
years), there were 27 hip fractures in the alendronate group and 73 in the no
alendronate group, corresponding to incidence rates of 9.5 (95% CI, 6.5-13.9) and
27.2 (95% CI, 21.6-34.2) fractures per 1000 person-years, with an absolute rate
difference of -17.6 (95% CI, -24.8 to -10.4). The use of alendronate was
associated with a lower risk of hip fracture in a multivariable-adjusted Cox
model (hazard ratio, 0.35; 95% CI, 0.22-0.54). Alendronate treatment was not
associated with increased risk of mild upper gastrointestinal tract symptoms
(alendronate vs no alendronate, 15.6 [95% CI, 11.6-21.0] vs 12.9 [95% CI, 9.3
18.0] per 1000 person-years; P = .40) or peptic ulcers (10.9 [95% CI, 7.7-15.5]
vs 11.4 [95% CI, 8.0-16.2] per 1000 person-years; P = .86). There were no cases
of incident drug-induced osteonecrosis and only 1 case of femoral shaft fracture
in each group. Conclusions and Relevance: Among older patients using medium to
high doses of prednisolone, alendronate treatment was associated with a
significantly lower risk of hip fracture over a median of 1.32 years. Although
the findings are limited by the observational study design and the small number
of events, these results support the use of alendronate in this patient group.
PMID- 28697257
TI - Stories Doctors Tell.
PMID- 28697259
TI - Behavioral Counseling to Promote a Healthful Diet and Physical Activity for
Cardiovascular Disease Prevention in Adults Without Known Cardiovascular Disease
Risk Factors: Updated Evidence Report and Systematic Review for the US Preventive
Services Task Force.
AB - Importance: Unhealthful dietary patterns, low levels of physical activity, and
high sedentary time increase the risk of cardiovascular disease. Objective: To
systematically review the evidence on the benefits and harms of behavioral
counseling for the primary prevention of cardiovascular disease in adults without
known cardiovascular risk factors to inform the US Preventive Services Task
Force. Data Sources: MEDLINE, PubMed, Cochrane Central Register of Controlled
Trials, and PsycINFO for studies published in the English language between
January 1, 2013, and May 25, 2016, and ongoing surveillance in targeted
publications through March 24, 2017. Studies included in the previous review were
reevaluated for inclusion. Study Selection: Randomized clinical trials of
behavioral interventions targeting improved diet, increased physical activity,
decreased sedentary time, or a combination of these among adults without known
hypertension, dyslipidemia, diabetes, or impaired fasting glucose. Data
Extraction and Synthesis: Independent critical appraisal and data abstraction by
2 reviewers. Main Outcomes and Measures: Cardiometabolic health and intermediate
outcomes, behavioral outcomes, and harms related to interventions. Results:
Eighty-eight studies (N = 121 190) in 145 publications were included. There was
no consistent benefit of the interventions on all-cause or cardiovascular
mortality or morbidity (4 trials [n = 51 356]) or health-related quality of life
(10 trials [n = 52 423]). There was evidence of small, statistically significant
between-group mean differences for systolic blood pressure (-1.26 mm Hg [95% CI,
1.77 to -0.75]; 22 trials [n = 57 953]), diastolic blood pressure (-0.49 mm Hg
[95% CI, -0.82 to -0.16]; 23 trials [n = 58 022]), low-density lipoprotein
cholesterol level (-2.58 mg/dL [95% CI, -4.30 to -0.85]; 13 trials [n = 5554]),
total cholesterol level (-2.85 mg/dL [95% CI, -4.95 to -0.75]; 19 trials [n =
9325]), and body mass index (-0.41 [95% CI, -0.62 to -0.19]; 20 trials [n = 55
059]) at 6 to 12 months as well as small-to-modest associations with dietary and
physical activity behaviors. There was no evidence of greater incidence of
serious adverse events, injuries, or falls in intervention vs control
participants. Conclusions and Relevance: Diet and physical activity behavioral
interventions for adults not at high risk for cardiovascular disease result in
consistent modest benefits across a variety of important intermediate health
outcomes across 6 to 12 months, including blood pressure, low-density lipoprotein
and total cholesterol levels, and adiposity, with evidence of a dose-response
effect, with higher-intensity interventions conferring greater improvements.
There is very limited evidence on longer-term intermediate and health outcomes or
on harmful effects of these interventions.
PMID- 28697261
TI - Toxic Mushrooms in California.
PMID- 28697260
TI - Behavioral Counseling to Promote a Healthful Diet and Physical Activity for
Cardiovascular Disease Prevention in Adults Without Cardiovascular Risk Factors:
US Preventive Services Task Force Recommendation Statement.
AB - Importance: Adults who adhere to national guidelines for a healthful diet and
physical activity have lower rates of cardiovascular morbidity and mortality than
those who do not. All persons, regardless of their risk status for cardiovascular
disease (CVD), can gain health benefits from healthy eating behaviors and
appropriate physical activity. Objective: To update the 2012 US Preventive
Services Task Force (USPSTF) recommendation on behavioral counseling to promote a
healthful diet and physical activity for cardiovascular disease prevention among
adults without obesity who do not have cardiovascular risk factors (hypertension,
dyslipidemia, abnormal blood glucose levels, or diabetes). Evidence Review: The
USPSTF reviewed the evidence on whether primary care-relevant counseling
interventions to promote a healthful diet, physical activity, or both improve
health outcomes, intermediate outcomes associated with CVD, or dietary or
physical activity behaviors in adults; interventions to reduce sedentary
behaviors; and the harms of behavioral counseling interventions. Findings:
Counseling interventions result in improvements in healthful behaviors and small
but potentially important improvements in intermediate outcomes, including
reductions in blood pressure and low-density lipoprotein cholesterol levels and
improvements in measures of adiposity. The overall magnitude of benefit related
to these interventions is positive but small. The potential harms are at most
small, leading the USPSTF to conclude that these interventions have a small net
benefit for adults without obesity who do not have CVD risk factors. Conclusions
and Recommendation: The USPSTF recommends that primary care professionals
individualize the decision to offer or refer adults without obesity who do not
have hypertension, dyslipidemia, abnormal blood glucose levels, or diabetes to
behavioral counseling to promote a healthful diet and physical activity. Existing
evidence indicates a positive but small benefit of behavioral counseling for the
prevention of CVD in this population. Persons who are interested and ready to
make behavioral changes may be most likely to benefit from behavioral counseling.
(C recommendation).
PMID- 28697262
TI - Conception Without HIV Transmission.
PMID- 28697263
TI - Community Primary Provider Involvement in Hospital Care.
PMID- 28697264
TI - Early Adversity, Toxic Stress, and Resilience: Pediatrics for Today.
AB - Never before in the history of science have we had better insight into the
factors that determine the health and well-being of a person from infancy to
adulthood. An expanding body of knowledge is converging from numerous disciplines
including neuroscience, education, behavioral science, public health, the social
sciences, and medicine. Awareness of the impact of early childhood adversity and
toxic stress is growing rapidly among both professionals and the lay public. This
calls for a reevaluation of how and what we, as child health care providers,
should deliver to maximize our impact on individual health and well-being across
the lifespan. This article briefly summarizes the topic and gives examples of how
child health care providers are innovatively incorporating the latest science in
practice. [Pediatr Ann. 2017;46(7):e246-e249.].
PMID- 28697265
TI - Pediatric Hospital Medicine.
PMID- 28697266
TI - Less is More: Evidence-Based Management of Bronchiolitis.
AB - Bronchiolitis is a common cause of outpatient visits and hospitalization in
children younger than age 2 years. Despite the frequency with which pediatricians
manage this diagnosis, there is significant variability in care in both the
inpatient and outpatient setting. This may be due in part to changing guidelines
set forth by leading pediatric organizations such as the American Academy of
Pediatrics, as increasing evidence emerges that traditional therapies are not
effective. This article reviews current evidence-based practices for diagnosis
and treatment of bronchiolitis, and provides an overview of inpatient management.
[Pediatr Ann. 2017;46(7):e252-e256.].
PMID- 28697267
TI - Back to the Basics: Community-Acquired Pneumonia in Children.
AB - Community-acquired pneumonia (CAP) is a common childhood infection and often a
reason for inpatient admission, especially when a child is hypoxic or in
respiratory distress. Despite advances in technology and diagnostics, it remains
difficult to accurately differentiate bacterial CAP from a viral process. Most of
the laboratory tests routinely done in inpatient medicine, such as complete blood
counts and acute phase reactants, do little to differentiate a viral pneumonia
from a bacterial pneumonia. Clinicians must rely heavily on the clinical
presentation and decide whether to treat empirically with antibiotics. Guidelines
published by the Infectious Disease Society of America in 2011 have helped
clinicians standardize the diagnosis and treatment of CAP. The guidelines
recommend relatively narrow-spectrum antibiotics, such as ampicillin or
penicillin, as empiric coverage for the fully immunized child older than age 3
months who requires hospitalization for CAP. [Pediatr Ann. 2017;46(7):e257
e261.].
PMID- 28697268
TI - The Cost of Hospital Admission: Brief Resolved Unexplained Events.
AB - The modern health care system continues to expand at a meteoric rate with ever
increasing technological advancements. However, with these advancements come
unsustainably rising costs and occasionally unintended, avoidable harm. In this
article, we use a brief resolved unexplained event (BRUE) to illustrate how
recent guidelines can help physicians practice value in this modern health care
system. A BRUE is a common pediatric problem that is seen in ambulatory and
emergency department settings. Infants presenting with a BRUE can be separated
into low- and high-risk groups per recent guidelines. Most low-risk infants who
present with a BRUE can be discharged home with anticipatory guidance, whereas
high-risk infants should undergo further testing and admission to determine the
cause of their event. [Pediatr Ann. 2017;46(7):e262-e264.].
PMID- 28697269
TI - Pediatric Cellulitis: A Red-Hot Concern.
AB - Cellulitis and other skin and soft tissue infections are a common reason for
children to seek care, both in the primary care setting and the emergency
department. Cellulitis is a common skin and soft-tissue infection that is usually
caused by streptococci bacteria or, less commonly, Staphylococcus aureus. Most
children recover quickly from cellulitis, but a small subset will require
hospitalization. Practitioners need to be skilled in the diagnosis and treatment
of cellulitis, including recognition of the need for inpatient treatment.
However, diagnosis of cellulitis, and exclusion of complicated or other more
serious infections, can be challenging. Management of these infections has also
been highly variable, resulting in some difficulty identifying the ideal
treatment regimen. The goal is to use the antibiotic with the narrowest spectrum
for the shortest duration necessary to provide clinical improvement. Research to
identify the best treatment for pediatric cellulitis will be important moving
forward. [Pediatr Ann. 2017;46(7):e265-e269.].
PMID- 28697270
TI - Lucy Maude Montgomery and Anne of Green Gables: An Early Description of Attention
Deficit/Hyperactivity Disorder.
AB - Attention-deficit/hyperactivity disorder (ADHD) was added to the Diagnostic and
Statistical Manual of Mental Disorders, third edition, revised in 1987. Similar
disorders had appeared earlier, and many consider the first description of ADHD
to be a lecture in 1902 about children with an "abnormal defect in moral control"
but normal intelligence. This definition of ADHD is more alarming than the
current one. Anne Shirley, the protagonist of the novel Anne of Green Gables
(written by Lucy Maude Montgomery and published in 1908), shares the hyperactive
and inattentive qualities that fit the current definition of ADHD. She also lacks
the menacing characteristics of the 1902 description. This indicates that ADHD,
by its modern definition, was probably present in the early 1900s. Furthermore,
the character of Anne Shirley shares many biographical similarities with her
author, suggesting that Montgomery herself may have had ADHD. Thus, looking at
literature from the past not only provides insight into the timeline of ADHD, but
also into the thought process of an individual with ADHD. By viewing literary
classics through a medical lens, we may gain insight into other diseases as well.
[Pediatr Ann. 2017; 46(7):e270-e272.].
PMID- 28697271
TI - Encouraging long-term outcomes reported in patients with stage I non-small cell
lung cancer treated with stereotactic ablative radiotherapy.
PMID- 28697272
TI - Screening of antigenic vesicular fluid proteins of Echinococcus multilocularis as
potential viability biomarkers to monitor drug response in alveolar
echinococcosis patients.
AB - PURPOSE: The only drugs available to treat alveolar echinococcosis (AE) are
mostly parasitostatic and in many cases prescribed for life. Decision criteria
for discontinuation rely on the absence of parasitic viability. The aim of the
present study is to search for candidate proteins that may exhibit good potential
as biomarkers for viability. EXPERIMENTAL DESIGN: Sixteen serum samples (five
healthy controls, 11 patients with AE), are used. AE-patients are classified into
three groups "Cured" (n = 2), "ABZ-responders" (n = 4) and "ABZ-nonresponders" (n
= 5). Immunoreactive proteins from vesicular fluid (VF) are identified and
quantified by LC-MS/MS analysis after immunoprecipitation (IP) using all 16 serum
samples. RESULTS: Shotgun analysis of VF lead to the identification of 107 E.
multilocularis proteins. Comparative proteomics reveal nine proteins more
abundant in IP eluates from ABZ-nonresponder patients (cathepsin b, prosaposin a
preprotein, actin modulator protein, fucosidase alpha L1 tissue, gluthatione-S
tranferase, beta galactosidase, elongation factor 2, H17g protein tegumental
antigen, and NiemannPick C2 protein). CONCLUSIONS AND CLINICAL RELEVANCE:
Detection of antibodies against these proteins by ELISA could be helpful to
monitor the course of alveolar echinococcosis under albendazole (ABZ) treatment.
PMID- 28697273
TI - Evidence supports the use of multidisciplinary team meetings.
PMID- 28697274
TI - Traceless Solid-Phase Synthesis of Fused Chiral Macrocycles via Conformational
Constraint-Assisted Cyclic Iminium Formation.
AB - Natural products comprising chiral molecular scaffolds containing fused medium
sized cycles and macrocycles represent an important and relevant pharmacological
target for the discovery and development of new drugs. Here, we describe
traceless solid-phase synthesis of acyclic intermediates amenable to cyclization
to medium (11) and large (12) fused rings. The key aspect of the synthetic
strategy is incorporation of a specific conformation constraint that facilitates
cyclization in favor of 11- and 12-membered rings rather than possible 7-membered
ones. The role of constraints in preorganization required for cyclization is
supported by computational analysis. The synthesis involves cyclic N
sulfonyliminium-nucleophilic addition chemistry as the key ring-forming reaction
and proceeds with complete stereocontrol of the newly formed stereogenic center.
We document the scope and limitations of this strategy in the synthesis of 11+5,
11+6, 11+7, and 12+6 fused rings representing molecular scaffolds with 3D
architecture that mimic complex natural products.
PMID- 28697275
TI - Potential Use of Multimodels in Consulting to Improve Model Acceptance and
Decision Making.
PMID- 28697276
TI - Comparative proteomic study of early hypoxic response in the cerebral cortex of
rats submitted to two different hypoxic models.
AB - PURPOSE: The present study analyses and compares the cortical brain proteomic
profiles of two different models of cerebral hypoxic insult in rats (HH:
hypobaric hypoxia and HHI: ischemia followed by hypobaric hypoxia) in an attempt
to describe the alterations of the early molecular hypoxic adaptive response
underlying each one. EXPERIMENTAL DESIGN: A quantitative proteomic profile of
left-brain cortices of rats under HH, HHI, and control conditions was determined
using isobaric labeling (Tandem Mass TagTM) on the protein extracts from pools of
five individuals. Data are available via ProteomeXchange with identifier
PXD004091. RESULTS: Altogether, 339 proteins were confidently quantified, 99 of
them showing significant variations in the hypoxic conditions with respect to the
control. The HHI model presents a global effect of protein downregulation while
HH produces an overall increase of the protein levels. While HH mainly affecting
oxidative and energetic metabolism, HHI also interferes with synaptic
transmission, neurotransmitter secretion, substantia nigra development, and
triggers apoptosis through mitochondrial pathway. CONCLUSIONS AND CLINICAL
RELEVANCE: The findings obtained show an overview of protein alterations under
two hypoxic models of different aetiology and provide a basis for more detailed
studies in order to unravel new specific mechanisms and therapies for hypoxic
pathologies.
PMID- 28697277
TI - Who Would Be Willing to Accept Disaster Debris in Their Backyard? Investigating
the Determinants of Public Attitudes in Post-Fukushima Japan.
AB - In the wake of the 2011 Great East Japan Earthquake and tsunami, the Ministry of
Environment in Japan asked municipalities nationwide to accept and treat disaster
waste. This call for cross-jurisdictional waste treatment provoked considerable
public controversy. To explore how the national and municipal governments can
seek more public acceptance in the wake of future disasters, this study
implemented a nationwide survey and addressed the question of what factors
influence the public's willingness to support their municipalities' plans to host
disaster waste. Three strands of the literature-on risk perception, public
dissent, and prosocial behavior-offer valuable insights into hypothesis building,
although none has addressed the above question. Estimates from an ordered
logistic regression (N = 1,063) reveal that the conditions of a nuclear accident
and living with a small child in the household would lower the level of support
for accepting disaster waste, although this does not mean that people would give
their support in the absence of a nuclear accident. The results also suggest that
the national and municipal governments should communicate more with the public
about the risks, benefits, and costs associated with hosting disaster debris, and
make efforts to improve public trust in the national government.
PMID- 28697278
TI - When more really means more: WGS standards and quality control.
PMID- 28697279
TI - Pathophysiologic effects of CHCHD2 variants associated with late-onset Parkinson
disease.
PMID- 28697280
TI - Postzygotic single nucleotide mosaicisms and autism risk.
PMID- 28697281
TI - Transport of the alpha subunit of the voltage gated L-type calcium channel
through the sarcoplasmic reticulum occurs prior to localization to triads and
requires the beta subunit but not Stac3 in skeletal muscles.
AB - Contraction of skeletal muscle is initiated by excitation-contraction (EC)
coupling during which membrane voltage is transduced to intracellular Ca2+
release. EC coupling requires L-type voltage gated Ca2+ channels (the
dihydropyridine receptor or DHPR) located at triads, which are junctions between
the transverse (T) tubule and sarcoplasmic reticulum (SR) membranes, that sense
membrane depolarization in the T tubule membrane. Reduced EC coupling is
associated with ageing, and disruptions of EC coupling result in congenital
myopathies for which there are few therapies. The precise localization of DHPRs
to triads is critical for EC coupling, yet trafficking of the DHPR to triads is
not well understood. Using dynamic imaging of zebrafish muscle fibers, we find
that DHPR is transported along the longitudinal SR in a microtubule-independent
mechanism. Furthermore, transport of DHPR in the SR membrane is differentially
affected in null mutants of Stac3 or DHPRbeta, two essential components of EC
coupling. These findings reveal previously unappreciated features of DHPR
motility within the SR prior to assembly at triads.
PMID- 28697282
TI - Exploring the potential of natural and synthetic neuroprotective steroids against
neurodegenerative disorders: A literature review.
AB - Neurodegeneration is a complex process, which leads to progressive brain damage
due to loss of neurons. Despite exhaustive research, the cause of neuronal loss
in various degenerative disorders is not entirely understood. Neuroprotective
steroids constitute an important line of attack, which could play a major role
against the common mechanisms associated with various neurodegenerative disorders
like Alzheimer's disease, Parkinson's disease, Huntington's disease, and
amyotrophic lateral sclerosis. Natural endogenous steroids induce the
neuroprotection by protecting the nerve cells from neuronal injury through
multiple mechanisms, therefore the structural modifications of the endogenous
steroids could be helpful in the generation of new therapeutically useful
neuroprotective agents. The review article will keep the readers apprised of the
detailed description of natural as well as synthetic neuroprotective steroids
from the medicinal chemistry point of view, which would be helpful in drug
discovery efforts aimed toward neurodegenerative diseases.
PMID- 28697283
TI - Ta(CNDipp)6 : An Isocyanide Analogue of Hexacarbonyltantalum(0).
AB - Hexakis(2,6-diisopropylphenylisocyanide)tantalum is the first isocyanide analogue
of the highly unstable Ta(CO)6 and represents the only well-defined zerovalent
tantalum complex to be prepared by conventional laboratory methods. Two prior
examples of homoleptic Ta0 complexes are known, Ta(benzene)2 and Ta(dmpe)3 ,
dmpe=1,2-bis(dimethylphosphano)ethane, but these have only been accessed via
ligand co-condensation with tantalum vapor in a sophisticated metal-atom reactor.
Consistent with its 17-electron nature, Ta(CNDipp)6 undergoes facile one-electron
oxidation, reduction, or disproportionation reactions. In this sense, it
qualitatively resembles V(CO)6 , the only paramagnetic homoleptic metal carbonyl
isolable under ambient conditions.
PMID- 28697284
TI - Community-Driven Hypothesis Testing: A Solution for the Tragedy of the
Anticommons.
AB - Shared ownership of property and resources is a longstanding challenge throughout
history that has been amplifying with the increasing development of industrial
and postindustrial societies. Where governments, project planners, and commercial
developers seek to develop new infrastructure, industrial projects, and various
other land-and resource-intensive tasks, veto power shared by various local
stakeholders can complicate or halt progress. Risk communication has been used as
an attempt to address stakeholder concerns in these contexts, but has
demonstrated shortcomings. These coordination failures between project planners
and stakeholders can be described as a specific kind of social dilemma that we
describe as the "tragedy of the anticommons." To overcome such dilemmas, we
demonstrate how a two-step process can directly address public mistrust of
project planners and public perceptions of limited decision-making authority.
This approach is examined via two separate empirical field experiments in
Portugal and Tunisia, where public resistance and anticommons problems threatened
to derail emerging industrial projects. In both applications, an intervention is
undertaken to address initial public resistance to such projects, where specific
public stakeholders and project sponsors collectively engaged in a hypothesis
testing process to identify and assess human and environmental health risks
associated with proposed industrial facilities. These field experiments indicate
that a rigorous attempt to address public mistrust and perceptions of power
imbalances and change the pay-off structure of the given dilemma may help
overcome such anticommons problems in specific cases, and may potentially
generate enthusiasm and support for such projects by local publics moving
forward.
PMID- 28697285
TI - An Expert Elicitation of the Proliferation Resistance of Using Small Modular
Reactors (SMR) for the Expansion of Civilian Nuclear Systems.
AB - To facilitate the use of nuclear energy globally, small modular reactors (SMRs)
may represent a viable alternative or complement to large reactor designs. One
potential benefit is that SMRs could allow for more proliferation resistant
designs, manufacturing arrangements, and fuel-cycle practices at widespread
deployment. However, there is limited work evaluating the proliferation
resistance of SMRs, and existing proliferation assessment approaches are not well
suited for these novel arrangements. Here, we conduct an expert elicitation of
the relative proliferation resistance of scenarios for future nuclear energy
deployment driven by Generation III+ light-water reactors, fast reactors, or
SMRs. Specifically, we construct the scenarios to investigate relevant technical
and institutional features that are postulated to enhance the proliferation
resistance of SMRs. The experts do not consistently judge the scenario with SMRs
to have greater overall proliferation resistance than scenarios that rely on
conventional nuclear energy generation options. Further, the experts disagreed on
whether incorporating a long-lifetime sealed core into an SMR design would
strengthen or weaken proliferation resistance. However, regardless of the type of
reactor, the experts judged that proliferation resistance would be enhanced by
improving international safeguards and operating several multinational fuel-cycle
facilities rather than supporting many more national facilities.
PMID- 28697286
TI - Annual Burden of Occupationally-Acquired Influenza Infections in Hospitals and
Emergency Departments in the United States.
AB - Infections among health-care personnel (HCP) occur as a result of providing care
to patients with infectious diseases, but surveillance is limited to a few
diseases. The objective of this study is to determine the annual number of
influenza infections acquired by HCP as a result of occupational exposures to
influenza patients in hospitals and emergency departments (EDs) in the United
States. A risk analysis approach was taken. A compartmental model was used to
estimate the influenza dose received in a single exposure, and a dose-response
function applied to calculate the probability of infection. A three-step
algorithm tabulated the total number of influenza infections based on: the total
number of occupational exposures (tabulated in previous work), the total number
of HCP with occupational exposures, and the probability of infection in an
occupational exposure. Estimated influenza infections were highly dependent upon
the dose-response function. Given current compliance with infection control
precautions, we estimated 151,300 and 34,150 influenza infections annually with
two dose-response functions (annual incidence proportions of 9.3% and 2.1%,
respectively). Greater reductions in infectious were achieved by full compliance
with vaccination and IC precautions than with patient isolation. The burden of
occupationally-acquired influenza among HCP in hospitals and EDs in the United
States is not trivial, and can be reduced through improved compliance with
vaccination and preventive measures, including engineering and administrative
controls.
PMID- 28697287
TI - Genetics of obesity.
AB - BACKGROUND: The prevalence and cost of overweight and obesity are projected to
continue to rise in our current sedentary, energy-rich environment. The
heritability of obesity is reported to be 40-80%. OBJECTIVE: The objectives of
this article are to review recent genetic discoveries about the basis of human
obesity; describe familial or syndromic obesity, which is rare but presents early
and should, if suspected, be referred for full specialist diagnosis of the
underlying genetic disorder; and summarise immediate implications for general
practice. DISCUSSION: Increasingly, specialised genetic studies are helping to
unravel the complex physiology underlying the regulation and control of body
fatness. Rare but serious syndromic obesity can now be identified early in life.
Possible targets for future drug treatment are currently being found and tested,
offering hope for the future. Understanding the heritable nature of obesity
should also help to relieve the blame and guilt from the professional's approach
to current weight management.
PMID- 28697288
TI - Obstructive sleep apnoea and obesity.
AB - BACKGROUND: Obstructive sleep apnoea (OSA) and obesity are two common conditions
affecting the Australian population; obesity is the major risk factor for OSA.
OBJECTIVE: The objectives of this article are to review the interactions between
obesity and OSA, including the increased cardiovascular risk, and highlight the
importance of using OSA diagnosis as a critical time to address obesity itself
and other cardiovascular risk factors. DISCUSSION: Snoring and symptoms of OSA
frequently worsen during periods of rapid weight gain. Obesity and metabolic
factors (eg hypertension, hyperlipidaemia, insulin resistance) are commonly
present at the time of OSA diagnosis. Severe OSA is an independent risk factor
for cardiovascular disease and stroke. Continuous positive airway pressure (CPAP)
treatment is safe and effective, reduces sleepiness, and improves mood and
quality of life; however, the cardiovascular benefits of CPAP are uncertain.
Weight loss leads to variable improvement in OSA, is most effective in milder
OSA, and has a greater benefit on cardiovascular risk than CPAP.
PMID- 28697289
TI - Bariatric-metabolic surgery: A guide for the primary care physician.
AB - BACKGROUND: Bariatric-metabolic surgery has emerged as an attractive option that
offers significant and durable weight loss in the treatment of clinically severe
obesity. Given the high prevalence of obesity, and growing numbers of bariatric
metabolic surgeries performed, primary care physicians increasingly encounter
patients who have had, or are considering, bariatric-metabolic surgery.
OBJECTIVE: The aim of this article is to provide guidance on common issues
pertaining to bariatric-metabolic surgery that general practitioners (GPs) face,
including patient selection, preoperative work-up, acute and long-term
complications following the surgery, and long-term lifestyle and nutritional
support. DISCUSSION: In properly selected patients with clinically severe
obesity, there is clear net benefit in terms of improved health outcomes and
reduced mortality following bariatric-metabolic surgery. Similarly to other
chronic conditions, GPs play a crucial role in the management of obesity, and in
the multidisciplinary, long-term postoperative support and monitoring that is
important for optimal outcomes after surgery.
PMID- 28697290
TI - Pharmacotherapy for obesity.
AB - BACKGROUND: Obesity is a serious, chronic, relapsing disease of energy
regulation, with strong genetic and early-life environmental determinants.
Pharmacotherapy can be a useful adjunct to lifestyle intervention in effecting
and maintaining clinically meaningful weight loss. OBJECTIVE: The aim of this
article is to discuss the role of pharmacotherapy in obesity management. The
efficacy, side effects and contraindications of available weight-loss medications
are reviewed. DISCUSSION: Long-term pharmacotherapy options, which can be
effective in providing moderate weight loss, are available to treat obesity.
Pharma-cotherapy should be considered an adjunct to lifestyle intervention in
those with a body mass index (BMI) >30 kg/m30 kg/m2, or in those with a BMI of 27
30 kg/m2 and obesity-related complications. Safety and efficacy should be
monitored closely on commencement, and the medication should be discontinued if
there are safety or tolerability issues, or if.
PMID- 28697291
TI - Genitourinary syndrome of menopause.
AB - BACKGROUND: Genitourinary syndrome of menopause (GSM) is the new term for
vulvovaginal atrophy (VVA). Oestrogen deficiency symptoms in the genitourinary
tract are bothersome in more than 50% of women, having an adverse impact on
quality of life, social activity and sexual relationships. GSM is a chronic and
progressive syndrome that is underdiagnosed and undertreated. OBJECTIVE: The aim
of this article is to increase knowledge and understanding of GSM, improving the
ability of healthcare professionals to discuss and obtain an appropriate history
sensitively, and treat accordingly. DISCUSSION: GSM includes conditions of the
vagina, vulva, pelvic floor tissues, urinary tract, and sexual dysfunction and
loss of libido. Many women are reluctant to report these symptoms to their
healthcare professional for many reasons.
PMID- 28697292
TI - Fragile X-associated disorders: Don't miss them.
AB - BACKGROUND: Fragile X-associated disorders are a family of inherited disorders
caused by expansions in the Fragile X Mental Retardation 1 (FMR1) gene.
Premutation expansions of the FMR1 gene confer risk for fragile X-associated
primary ovarian insufficiency and fragile X-associated tremor ataxia syndrome, as
well as other medical and psychiatric comorbidities. Premutation expansions of
the FMR1 gene are common in the general population. However, fragile X-associated
disorders are frequently under-recognised and often misdiagnosed. OBJECTIVE: The
aim of this article is to describe fragile X-associated disorders and identify
specific considerations for general practitioners (GPs) during identification and
management of these disorders. DISCUSSION: GPs have a critical role in the
identification of fragile X-associated disorders, as well as coordination of
complex care needs. Prompt recognition and appropriate management of these
disorders and potential medical and psychiatric comorbidities will have important
implications not only for the affected patient, but also other family members who
may be at risk.
PMID- 28697293
TI - Chronic lymphocytic leukaemia: An updated approach to diagnosis and management in
general practice.
AB - BACKGROUND: Chronic lymphocytic leukaemia (CLL) is the most common
lymphoproliferative disease in Australia. Improvements in the understanding of
this disease have led to drastic changes in regards to diagnosis, management and
prognosis. OBJECTIVE: The aim of this article is to give an updated approach to
the diagnosis, investigation, monitoring and new treatments of CLL. DISCUSSION:
With the advent of new medications and improved investigations to predict
outcomes, CLL has now become a chronic disease that requires long-term monitoring
by haematologists and general practitioners (GPs).
PMID- 28697294
TI - Clinical assessment, diagnosis and management of nasal obstruction.
AB - BACKGROUND: Nasal obstruction is among the most common complaints to the general
practitioner (GP). Causes can be divided into mucosal causes or anatomical
abnormalities. Most mucosal pathologies can be managed effectively in the primary
care setting, with referral to the otolaryngologist in cases that are resistant
to medical therapy and in cases of structural anomaly. In cases of allergy,
referral to an immunologist may be beneficial. OBJECTIVE: The aim of this article
is to review the clinical assessment and management of nasal obstruction in the
primary care setting. We consider the various causes of nasal obstruction,
describe their management and define those cases that require specialist
referral. DISCUSSION: Nasal obstruction may be acute or chronic and is a
manifestation of a wide range of disease processes, most of which are managed by
the GP. In patients with persistent nasal obstruction and in those with
structural abnormalities, specialist referral is warranted.
PMID- 28697295
TI - Using electronic medical records to assess the rate of treatment for osteoporosis
in Australia.
AB - BACKGROUND: Despite available Medicare Benefits Schedule subsidies, it has been
suggested that screening and treatment for osteoporosis are under-accessed in
Australia, particularly in patients >=70 years. This study describes the rate of
osteoporosis treatment in those aged >=70 years in regional New South Wales as
identified in the electronic medical records (EMR) of 11 general practices.
METHODS: EMR data were extracted using a Canning Tool adaptation. The prevalence
of osteoporosis, fracture and bone-active medication prescriptions were
described, and associations examined. RESULTS: Osteoporosis was identified in 728
patients (20.9%) - 28.6% females and 9.4% males - with 70.6% of these patients
prescribed active medication. Diagnosis increased with fracture history (odds
ratio [OR]: 6.65; 95% confidence interval [CI]: 5.22, 8.47), female gender (OR:
3.38; 95% CI: 2.73, 4.16) and each year older (OR: 1.04; 95% CI: 1.02, 1.05).
Treatment was negatively associated with patients aged >=90 years versus patients
aged 70-79 years (OR: 0.5; 95% CI: 0.3, 0.9). DISCUSSION: This study suggests
that treatment for osteoporosis is suboptimal. The use of EMR data could be used
for audit or monitoring of interventions in general practice.
PMID- 28697296
TI - Hepatitis B testing and diagnosis experiences of patients and primary care
professionals in Australia.
AB - OBJECTIVE: A significant proportion of Australians with chronic hepatitis B (CHB)
remains undiagnosed and unaware of their risk of liver disease and cancer. This
study explored the hepatitis B testing and diagnostic experiences of people with
CHB, general practitioners (GPs) and primary care nurses. METHODS: Semi
structured interviews were conducted with people who have CHB (n = 19), GPs (n =
14) and nurses (n = 5). RESULTS: The majority of patient participants with CHB
were not provided with information prior to being tested, and were shocked to
receive a diagnosis. Neither GPs nor nurses noted Australia's National hepatitis
B testing policy as guiding their practice, and hepatitis B con-tact tracing was
poorly executed. DISCUSSION: Patient participants' diagnostic experiences did not
correspond with national policy recommendations. GPs and nurses need resources to
provide accurate information when testing and diagnosing hepatitis B, and clear
guidance about their role in contact tracing.
PMID- 28697297
TI - General practitioner follow-up in older patients after an emergency department
admission.
AB - BACKGROUND: Few studies have investigated older patients with regards to general
practice follow-up after an emergency department (ED) admission. We measured the
proportion of older patients given explicit general practice follow-up
instructions who sought care by day seven after an ED admission. METHODS:
Patients discharged from Fairfield Hospital ED (south-western Sydney) who were 65
years and older were approached for a structured telephone interview. Data from
the interview and patients' ED discharge summaries were analysed descriptively.
Exploratory statistical analyses were conducted to identify potential explanatory
factors. RESULTS: Fifty patients participated in the study. Most participants
(76%) attended general practice follow-up by day seven. Those with more relatives
who could be called on for help were more likely to attend the follow-up
appointment (P = 0.003). Participants who were not married (54% versus 84%) and
non-drivers (53% versus 90%) were less likely to attend for follow-up.
DISCUSSION: Close family support and car transport might influence general
practice follow-up in older people. Further exploration of contributing factors
may be warranted.
PMID- 28697298
TI - Successfully implementing a diabetic retinopathy screening service in general
practice: What does the evidence tell us?
AB - BACKGROUND: We previously showed that general-practice based screening for
diabetic retinopathy significantly improves recording of screening outcomes and
follow-up for Australians with type 2 diabetes. In 2016, two Medicare Benefits
Schedule item numbers were launched to support screening in general practice.
However, there is little evidence-based information to guide practices in
successfully implementing screening models for diabetic retinopathy. The
objective of this study was to develop an evidence-based framework to guide
successful general-practice based screening for diabetic retinopathy. METHODS:
Thematic analysis was used to identify and classify recurrent themes from
qualitative and observational data gathered from general practices and staff
undertaking successful screening for diabetic retinopathy. RESULTS: Seven themes
(a combination of enablers and potential risks) were identified as key components
of successful screening for diabetic retinopathy in general practice.
PMID- 28697299
TI - Beneath the tip of the iceberg: Why so many people with eating disorders are not
referred for treatment.
PMID- 28697300
TI - Direct Laser Writing of Tubular Microtowers for 3D Culture of Human Pluripotent
Stem Cell-Derived Neuronal Cells.
AB - As the complex structure of nervous tissue cannot be mimicked in two-dimensional
(2D) cultures, the development of three-dimensional (3D) neuronal cell culture
platforms is a topical issue in the field of neuroscience and neural tissue
engineering. Computer-assisted laser-based fabrication techniques such as direct
laser writing by two-photon polymerization (2PP-DLW) offer a versatile tool to
fabricate 3D cell culture platforms with highly ordered geometries in the size
scale of natural 3D cell environments. In this study, we present the design and
2PP-DLW fabrication process of a novel 3D neuronal cell culture platform based on
tubular microtowers. The platform facilitates efficient long-term 3D culturing of
human neuronal cells and supports neurite orientation and 3D network formation.
Microtower designs both with or without intraluminal guidance cues and/or
openings in the tower wall are designed and successfully fabricated from
Ormocomp. Three of the microtower designs are chosen for the final culture
platform: a design with openings in the wall and intralumial guidance cues (webs
and pillars), a design with openings but without intraluminal structures, and a
plain cylinder design. The proposed culture platform offers a promising concept
for future 3D cultures in the field of neuroscience.
PMID- 28697301
TI - Discovery of a Membrane-Active, Ring-Modified Histidine Containing Ultrashort
Amphiphilic Peptide That Exhibits Potent Inhibition of Cryptococcus neoformans.
AB - The new structural classes of ultrashort peptides that exhibit potent
microbicidal action have potential as future drugs. Herein, we report that C-2
arylated histidines containing tripeptides His(2-Ar)-Trp-His(2-Ar) exhibit potent
antifungal activity against Cryptococcus neoformans with high selectivity. The
most potent peptide 12f [His(2-biphenyl)-Trp-His(2-biphenyl)] displayed high in
vitro activity against C. neoformans (IC50 = 0.35 MUg/mL, MIC = MFC = 0.63
MUg/mL) with a selectivity index of >28 and 2 times higher potency compared to
amphotericin B. Peptide 12f exhibited proteolytic stability, with no apparent
hemolytic activity. The mechanism of action study of 12f by confocal laser
scanning microscopy and electron microscopy indicates nuclear fragmentation and
membrane disruption of C. neoformans cells. Combinations of 12f with fluconazole
and amphotericin B at subinhibitory concentration were synergistic against C.
neoformans. This study suggests that 12f is a new structural class of amphiphilic
peptide with rapid fungicidal activity caused by C. neoformans.
PMID- 28697302
TI - Discovery and Characterization of 1H-Pyrazol-5-yl-2-phenylacetamides as Novel,
Non-Urea-Containing GIRK1/2 Potassium Channel Activators.
AB - The G protein-gated inwardly-rectifying potassium channels (GIRK, Kir3) are a
family of inward-rectifying potassium channels, and there is significant evidence
supporting the roles of GIRKs in a number of physiological processes and as
potential targets for numerous indications. Previously reported urea containing
molecules as GIRK1/2 preferring activators have had significant pharmacokinetic
(PK) liabilities. Here we report a novel series of 1H-pyrazolo-5-yl-2
phenylacetamides in an effort to improve upon the PK properties. This series of
compounds display nanomolar potency as GIRK1/2 activators with improved brain
distribution (rodent Kp > 0.6).
PMID- 28697303
TI - Machine Learning Approach for Prediction and Understanding of Glass-Forming
Ability.
AB - The prediction of the glass-forming ability (GFA) by varying the composition of
alloys is a challenging problem in glass physics, as well as a problem for
industry, with enormous financial ramifications. Although different empirical
guides for the prediction of GFA were established over decades, a comprehensive
model or approach that is able to deal with as many variables as possible
simultaneously for efficiently predicting good glass formers is still highly
desirable. Here, by applying the support vector classification method, we develop
models for predicting the GFA of binary metallic alloys from random compositions.
The effect of different input descriptors on GFA were evaluated, and the best
prediction model was selected, which shows that the information related to
liquidus temperatures plays a key role in the GFA of alloys. On the basis of this
model, good glass formers can be predicted with high efficiency. The prediction
efficiency can be further enhanced by improving larger database and refined input
descriptor selection. Our findings suggest that machine learning is very powerful
and efficient and has great potential for discovering new metallic glasses with
good GFA.
PMID- 28697304
TI - Low Variability in Synthetic Monolayer MoS2 Devices.
AB - Despite much interest in applications of two-dimensional (2D) fabrics such as
MoS2, to date most studies have focused on single or few devices. Here we examine
the variability of hundreds of transistors from monolayer MoS2 synthesized by
chemical vapor deposition. Ultraclean fabrication yields low surface roughness of
~3 A and surprisingly low variability of key device parameters, considering the
atomically thin nature of the material. Threshold voltage variation and very low
hysteresis suggest variations in charge density and traps as low as ~1011 cm-2.
Three extraction methods (field-effect, Y-function, and effective mobility)
independently reveal mobility from 30 to 45 cm2/V/s (10th to 90th percentile;
highest value ~48 cm2/V/s) across areas >1 cm2. Electrical properties are
remarkably immune to the presence of bilayer regions, which cause only small
conduction band offsets (~55 meV) measured by scanning Kelvin probe microscopy,
an order of magnitude lower than energy variations in Si films of comparable
thickness. Data are also used as inputs to Monte Carlo circuit simulations to
understand the effects of material variability on circuit variation. These
advances address key missing steps required to scale 2D semiconductors into
functional systems.
PMID- 28697305
TI - Optimizing Multistep Delivery of PEGylated Tumor-Necrosis-Factor-Related
Apoptosis-Inducing Ligand-Toxin Conjugates for Improved Antitumor Activities.
AB - Although TRAIL (tumor-necrosis-factor (TNF)-related apoptosis-inducing ligand)
has been considered a promising broad-spectrum antitumor agent, its further
application was limited by poor drug delivery and TRAIL-resistant tumors. A three
step drug delivery strategy was applied to TRAIL for solving these two obstacles
in the form of PEG-TRAIL-MMAE (Monomethyl Auristatin E). PEGylation of TRAIL in
the first step was carried out to improve its in vivo pharmacokinetics, while the
interaction between TRAIL conjugates with death receptors in the second step was
designed to activate the TRAIL extrinsic apoptosis pathway, and the further
release of MMAE from the lysosome was the third step for introducing another
apoptosis pathway to overcome TRAIL resistance in some tumors. Herein, in order
to reach a balance among the three steps, the PEG/MMAE ratio was optimized for
PEG-TRAIL-MMAE conjugates. PEG-TRAIL-MMAE conjugates with various PEG/MMAE ratios
were prepared and compared with each other regarding their pharmacokinetics (PK)
and pharmacodynamics (PD). As a result, PEG-TRAIL-MMAE conjugates with a PEG/MMAE
ratio of 1:2 showed prolonged half-life in rats (6.8 h), and the best antitumor
activity in vitro (IC50 0.31 nM) and in vivo while no sign of toxicity in
xenograft models, suggesting it as a promising multistep drug delivery and
antitumor strategy after optimization.
PMID- 28697306
TI - Trackable Mitochondria-Targeting Nanomicellar Loaded with Doxorubicin for
Overcoming Drug Resistance.
AB - Multidrug resistance (MDR) has been recognized as a major obstacle to successful
chemotherapy for cancer in the clinic. In recent years, more and more nanoscaled
drug delivery systems (DDS) are constructed to modulate drug efflux protein (P
gp) and deliver chemotherapeutic drugs for overcoming MDR. Among them, d-alpha
tocopheryl polyethylene glycol succinate (TPGS) has been widely used as a drug
carrier due to its capability of inhibiting overexpression of P-gp and good
amphiphilicity favorable for improving permeation and long-circulation property
of DDS. In the present work, a novel kind of mitochondria-targeting nanomicelles
based DDS is developed to integrate chemotherapeutics delivery with fluorescence
imaging functionalities on a comprehensive nanoplatform. The mitochondria
targeting nanomicelles are prepared by self-assembly of triphenylphosphine (TPP)
modified TPGS and fluorescent carbon quantum dots (CQDs) in an n-hexane/H2O mixed
solution, named CQDs-TPGS-TPP. Notably, although the drug loading content of
doxorubicin (DOX) in the as-prepared nanomicelles is as low as 3.4%, the
calculated resistant index (RI) is greatly decreased from 66.23 of free DOX to
7.16 of DOX-loaded nanomicelles while treating both parental MCF-7 cells and drug
resistant MCF-7/ADR cells. Compared with free DOX, the penetration efficiency of
DOX-loaded nanomicelles in three-dimensional multicellular spheroids (MCs) of MCF
7/ADR is obviously increased. Moreover, the released DOX from the nanomicelles
can cause much more damage to cells of drug-resistant MCs. These results
demonstrate that our constructed mitochondria-targeting nanomicelles-based DDS
have potential application in overcoming MDR of cancer cells as well as their MCs
that mimic in vivo tumor tissues. The MDR-reversal mechanism of the DOX-loaded
CQDs-TPGS-TPP nanomicelles is also discussed.
PMID- 28697307
TI - Prawn Shell Derived Chitin Nanofiber Membranes as Advanced Sustainable Separators
for Li/Na-Ion Batteries.
AB - Separators, necessary components to isolate cathodes and anodes in Li/Na-ion
batteries, are consumed in large amounts per year; thus, their sustainability is
a concerning issue for renewable energy storage systems. However, the eco
efficient and environmentally friendly fabrication of separators with a high
mechanical strength, excellent thermal stability, and good electrolyte
wettability is still challenging. Herein, we reported the fabrication of a new
type of separators for Li/Na-ion batteries through the self-assembly of eco
friendly chitin nanofibers derived from prawn shells. We demonstrated that the
pore size in the chitin nanofiber membrane (CNM) separator can be tuned by
adjusting the amount of pore generation agent (sodium dihydrogen citrate) in the
self-assembly process of chitin nanofibers. By optimizing the pore size in CNM
separators, the electrochemical performance of the LiFePO4/Li half-cell with a
CNM separator is comparable to that with a commercialized polypropylene (PP)
separator. More attractively, the CNM separator showed a much better performance
in the LiFePO4/Li cell at 120 degrees C and Na3V2(PO4)3/Na cell than the PP
separator. The proposed fabrication of separators by using natural raw materials
will play a significant contribution to the sustainable development of renewable
energy storage systems.
PMID- 28697308
TI - Evaluation of Life Cycle Assessment (LCA) for Roadway Drainage Systems.
AB - Roadway drainage design has traditionally focused on cost-effectively managing
water quantity; however, runoff carries pollutants, posing risks to the local
environment and public health. Additionally, construction and maintenance incur
costs and contribute to global environmental impacts. While life cycle assessment
(LCA) can potentially capture local and global environmental impacts of roadway
drainage and other stormwater systems, LCA methodology must be evaluated because
stormwater systems differ from wastewater and drinking water systems to which LCA
is more frequently applied. To this end, this research developed a comprehensive
model linking roadway drainage design parameters to LCA and life cycle costing
(LCC) under uncertainty. This framework was applied to 10 highway drainage
projects to evaluate LCA methodological choices by characterizing environmental
and economic impacts of drainage projects and individual components (basin,
bioswale, culvert, grass swale, storm sewer, and pipe underdrain). The relative
impacts of drainage components varied based on functional unit choice. LCA
inventory cutoff criteria evaluation showed the potential for cost-based
criteria, which performed better than mass-based criteria. Finally, the local
aquatic benefits of grass swales and bioswales offset global environmental
impacts for four impact categories, highlighting the need to explicitly consider
local impacts (i.e., direct emissions) when evaluating drainage technologies.
PMID- 28697309
TI - Identification of Natural Products That Inhibit the Catalytic Function of Human
Tyrosyl-DNA Phosphodiesterase (TDP1).
AB - Tyrosyl-DNA phosphodiesterase 1 (TDP1) is an enzyme crucial for cleavage of the
covalent topoisomerase 1-DNA complex, an intermediate in DNA repair. TDP1 plays a
role in reversing inhibition of topoisomerase I by camptothecins, a series of
potent and effective inhibitors used in the treatment of colorectal, ovarian, and
small-cell lung cancers. It is hypothesized that inhibition of TDP1 activity may
enhance camptothecin sensitivity in tumors. Here, we describe the design,
development, and execution of a novel assay to identify inhibitors of TDP1
present in natural product extracts. The assay was designed to address issues
with fluorescent "nuisance" molecules and to minimize the detection of false
positives caused by polyphenolic molecules known to nonspecifically inhibit
enzyme activity. A total of 227,905 purified molecules, prefractionated extracts,
and crude natural product extracts were screened. This yielded 534 initial
positives (0.23%). Secondary prioritization reduced this number to 117 (0.05%
final hit rate). Several novel inhibitors have been identified showing micromolar
affinity for human TDP1, including halenaquinol sulfate, a pentacyclic
hydroquinone from the sponge Xestospongia sp.
PMID- 28697310
TI - Hypermobile Pulsatile Eardrum Attributable to Temporal Bone Metastasis.
PMID- 28697311
TI - Breast cancer treatment-induced cardiotoxicity.
AB - INTRODUCTION: Breast cancer is the most frequent cancer affecting women
worldwide. In every setting, the majority of women are treated with an
evergrowing arsenal of therapeutic agents that have greatly improved their
outcomes. However, these therapies can also be associated with significant
adverse events. Areas covered: This review aims to thoroughly describe the
current state of the evidence regarding the potential cardiotoxicity of agents
commonly used in the treatment of breast cancer. These include chemotherapeutic
agents, anti-HER2 therapies and CDK4/6 and mTOR inhibitors. Furthermore, issues
related to the risk stratification and monitoring tools are explored. Expert
opinion: Anthracycline- and trastuzumab-related cardiac toxicities have been
extensively studied. Substantial evidence is now available concerning additional
anti-HER2 agents such as pertuzumab, T-DM1 and tyrosine kinase inhibitors;
overall, the cardiotoxicity profile is reassuring. Cardiac events due to
endocrine therapy are mostly ischemic and, in the context of prolonged therapy,
need specific attention. Novel agents implicated in the treatment of hormone
receptor-positive disease are potentially arrhythmogenic and the exact risk will
need to be further refined. As for today, assessment of baseline risk factors
prior to treatment initiation and cardiac imaging before and during treatment
remains the optimal way to prevent cardiac dysfunction. Cardioprotective therapy
in primary prevention is still a matter of debate.
PMID- 28697312
TI - Proteome analysis of irradiated endothelial cells reveals persistent alteration
in protein degradation and the RhoGDI and NO signalling pathways.
AB - PURPOSE: Epidemiological studies indicate that radiation doses as low as 0.5 Gy
increase the risk of cardiovascular disease decades after the exposure. The aim
of the present study was to investigate whether this radiation dose causes late
molecular alterations in endothelial cells that could support the population
based data. MATERIALS AND METHODS: Human coronary artery endothelial cells were
irradiated at 0.5 Gy (X-ray) and radiation-induced changes in the proteome were
investigated after different time intervals (1, 7 and 14 d) using ICPL
technology. Key changes identified by proteomics and bioinformatics were
validated by immunoblotting and ELISA. RESULTS: The radiation-induced alteration
of the endothelial proteome was characterized by sustained perturbation of Rho
GDP-dissociation inhibitor (RhoGDI) and nitric oxide (NO) signalling pathways. At
later time-points, this was accompanied by reduced proteasome activity, enhanced
protein carbonylation indicating augmented oxidative stress, and senescence.
CONCLUSIONS: These molecular changes are indicative of long-term premature
endothelial dysfunction and provide a mechanistic framework to the
epidemiological data showing increased risk of cardiovascular disease at 0.5 Gy.
PMID- 28697313
TI - Rifamycin SV MMX for the treatment of traveler's diarrhea.
AB - INTRODUCTION: Rifamycin SV MMX(r), a non-absorbable rifamycin antibiotic
formulated using the multi-matrix system, was designed to exhibit its
pharmacological action on the distal small intestine and colon. Its clinical
efficacy and safety profile in the treatment of traveler's diarrhea were
evaluated in several clinical studies. Areas covered: This review summarizes all
available evidence regarding clinical trials of the efficacy and safety profile
of rifamycin SV MMX for the treatment of traveler's diarrhea. Expert opinion:
Rifamycin SV MMX demonstrated an excellent pharmacokinetic profile with decreased
systemic toxicity similar to rifaximin. In phase II and phase III clinical
trials, concerns have been raised regarding the medicine's efficacy in terms of
the time to last unformed stool and cure rate compared to current recommended
antibiotics in the treatment of acute diarrhea caused by diarrheagenic
Escherichia coli and invasive pathogens. The significance of the increase in MICs
after the use of rifamycin SV MMX warrants further examination.
PMID- 28697314
TI - Grainyhead-like Transcription Factors in Craniofacial Development.
AB - Craniofacial development in vertebrates involves the coordinated growth,
migration, and fusion of several facial prominences during embryogenesis,
processes governed by strict genetic and molecular controls. A failure in any of
the precise spatiotemporal sequences of events leading to prominence fusion often
leads to anomalous facial, skull, and jaw formation-conditions termed
craniofacial defects (CFDs). Affecting approximately 0.1% to 0.3% of live births,
CFDs are a highly heterogeneous class of developmental anomalies, which are often
underpinned by genetic mutations. Therefore, identifying novel disease-causing
mutations in genes that regulate craniofacial development is a critical
prerequisite to develop new preventive or therapeutic measures. The Grainyhead
like ( GRHL) transcription factors are one such gene family, performing
evolutionarily conserved roles in craniofacial patterning. The antecedent member
of this family, Drosophila grainyhead ( grh), is required for head skeleton
development in fruit flies, loss or mutation of Grhl family members in mouse and
zebrafish models leads to defects of both maxilla and mandible, and recently,
mutations in human GRHL3 have been shown to cause or contribute to both syndromic
(Van Der Woude syndrome) and nonsyndromic palatal clefts. In this review, we
summarize the current knowledge regarding the craniofacial-specific function of
the Grainyhead-like family in multiple model species, identify some of the major
target genes regulated by the Grhl transcription factors in craniofacial
patterning, and, by examining animal models, draw inferences as to how these data
will inform the likely roles of GRHL factors in human CFDs comprising palatal
clefting. By understanding the molecular networks regulated by Grhl2 and Grhl3
target genes in other systems, we can propose likely pathways that mediate the
effects of these transcription factors in human palatogenesis.
PMID- 28697315
TI - An update on anesthetics and impact on the brain.
AB - INTRODUCTION: While anesthetics are indispensable clinical tools and generally
considered safe and effective, a growing concern over the potential neurotoxicity
of anesthesia or specific anesthetic agents has called into question the safety
of general anesthetics, especially when administered at extremes of age. Areas
covered: This article reviews and updates research findings on the safety of
anesthesia and anesthetics in terms of long-term neurotoxicity, with particular
focus on postoperative cognitive dysfunctions, Alzheimer's disease and dementias,
developing brain, post-operative depression and autism spectrum disorder. Expert
opinion: Exposure to general anesthetics is potentially harmful to the human
brain, and the consequent long-term cognitive deficits should be classified as an
iatrogenic pathology, and considered a public health problem. The fact that in
laboratory and clinical research only certain anesthetic agents and techniques,
but not others, appear to be involved, raises the problem on what is the safest
and the least safe anesthetic to maximize anesthesia efficiency, avoid occurrence
of adverse events, and ensure patient safety. New trends in research are moving
toward the theory that neuroinflammation could be the hallmark of, or could have
a pivotal role in, several neurological disorders.
PMID- 28697316
TI - Renal Medullary Carcinoma: The Kidney Cancer That Affects Individuals With Sickle
Cell Trait and Disease.
PMID- 28697317
TI - Management of Malignant Bowel Obstruction Associated With GI Cancers.
AB - For many patients with GI malignancies, the seeding of the abdominal cavity with
tumor cells, called peritoneal carcinomatosis, is a common mode of metastases and
disease progression. Prognosis for patients with this aspect of their disease
remains poor, with high disease-related morbidity and complications. Uniform and
proven practices that provide optimal palliative care and quality of life for
these patients are needed. The objective of this review is to critically assess
the current literature regarding palliative strategies in the management of
peritoneal carcinomatosis and associated symptoms in patients with advanced GI
cancers. Despite encouraging results in the select population where cytoreductive
surgery and intraperitoneal chemotherapy are indicated, the majority of patients
who develop peritoneal carcinomatosis in the setting of GI cancers have poor
prognosis, with malignant bowel obstruction representing a common terminal phase
of their disease process. For all patients with peritoneal carcinomatosis,
aggressive symptom control and early multimodality palliative care as further
outlined should be sought.
PMID- 28697318
TI - Errata.
PMID- 28697320
TI - Errata.
PMID- 28697321
TI - Managing Malignant Bowel Obstruction: Moving Beyond Drip and Suck.
PMID- 28697319
TI - Renal Medullary Carcinoma: Establishing Standards in Practice.
AB - Although renal medullary carcinoma (RMC) is a rare subtype of kidney cancer, it
is particularly devastating in that it is nearly uniformly lethal. No established
guidelines exist for the diagnosis and management of RMC. In April 2016, a panel
of experts developed clinical guidelines on the basis of a literature review and
consensus statements. The goal was to propose recommendations for standardized
diagnostic and management approaches and to establish an international clinical
registry and biorepository for RMC. Published data are limited to case reports
and small retrospective reviews. The RMC Working Group prepared recommendations
to inform providers and patients faced with a low level of medical evidence. The
diagnosis of RMC should be considered in all patients younger than 50 years with
poorly differentiated carcinoma that arises from the renal medulla. These
patients should be tested for sickle cell hemoglobinopathies, and if positive,
SMARCB1/INI1 loss should be confirmed by immunohistochemistry. The majority of
patients with RMC are diagnosed with metastatic disease. Upfront radical
nephrectomy should be considered in patients with good performance status and low
metastatic burden or after response to systemic therapy. Currently, cytotoxic,
platinum-based chemotherapy provides the best, albeit brief, palliative clinical
benefit. Vascular endothelial growth factor-directed therapies and mammalian
target of rapamycin inhibitors are ineffective in RMC as monotherapy. Therapeutic
trials of novel agents are now available for RMC, and every effort should be made
to enroll patients in clinical studies.
PMID- 28697322
TI - Many Challenges of Peritoneal Carcinomatosis.
PMID- 28697323
TI - Errata.
PMID- 28697324
TI - Renal Medullary Carcinoma.
PMID- 28697325
TI - Direct-to-consumer DNA testing: the fallout for individuals and their families
unexpectedly learning of their donor conception origins.
AB - Increasing numbers of donor-conceived individuals (and/or parents) are seeking
individuals genetically related through donor conception. One route is through
'direct-to-consumer' (DTC) DNA testing, prompting calls for fertility services to
alert donors and prospective parents to the increasing unsustainability of
anonymity and secrecy. The complexity of interpreting DNA results in this context
has also been discussed, including their lack of absolute certainty, as has the
need for professional and peer support. This commentary highlights a different
'threat', from individuals learning of their donor-conception origins through the
use of such tests by themselves or relatives for such purposes as genealogy or
health checks. It illustrates the personal complexities faced by three older
women and their families on learning not only of their genetic relationship to
each other but also to 15 more donor-related siblings. DTC DNA services are a
growing feature of modern life. This commentary raises ethical questions about
their responsibilities towards those inadvertently learning of donor conception
origins and the responsibilities of fertility services to inform prospective
parents and donors of this new phenomenon. Considerations of how and when parents
should tell their children of their donor-conception origins here instead become
how and when children should inform their parents.
PMID- 28697326
TI - Laminin-Dependent Interaction between Astrocytes and Microglia: A Role in Retinal
Angiogenesis.
AB - Retinal vascular diseases are among the leading causes of acquired blindness. In
recent years, retinal microglia have been shown to influence vascular branching
density and endothelial cell proliferation. However, how microglial recruitment
and activation are regulated during development remains unclear. We hypothesized
that microglial recruitment, activation, and down-stream signaling are modulated
by components of the mural basement membrane. We used a reverse genetic approach
to disrupt laminin expression in the vascular basement membrane and demonstrate
that microglia respond to the mural basement membrane in an isoform-specific
manner. Microglial density is significantly increased in the laminin gamma3-null
(Lamc3-/-) retinal superficial vascular plexus and consequently the vascular
branching density is increased. Microglia also respond to astrocyte-derived
matrices and become hyperactivated in the Lamc3-/- retina or when tested in vitro
with cell-derived matrix. Pharmacological activation of microglia in the wild
type retina produced an Lamc3-/--like vascular phenotype, whereas pharmacological
blocking of microglial activation in the Lamc3-/- retina rescued the wild-type
vascular phenotype. On the molecular level, microglial transforming growth factor
beta1 expression is down-regulated in the Lamc3-/- retina, and SMAD signaling
decreased in endothelial cells with a consequent increase in endothelial
proliferation. The reverse effects were seen in the Lamb2-/- retina. Together,
our results demonstrate a novel mechanism by which laminins modulate vascular
branching and endothelial cell proliferation during retinal angiogenesis.
PMID- 28697327
TI - Reply by Authors.
PMID- 28697328
TI - Editorial Comment.
PMID- 28697329
TI - Lipid Droplets Guard Mitochondria during Autophagy.
AB - In this issue of Developmental Cell, Nguyen et al. (2017) show that lipid
droplets serve a dual purpose during starvation. First, they act as an energy
source by supplying fatty acids for mitochondrial beta oxidation. Second, they
sequester toxic lipids that arise during autophagic degradation of membranous
organelles, thereby protecting mitochondria.
PMID- 28697330
TI - RA Gets Out of the Way to Allow High-Acuity Vision.
AB - Specialized areas in the vertebrate retina are critical for high-acuity vision,
yet the molecular mechanisms driving the development of high-acuity areas (HAAs)
remain largely unknown. In Developmental Cell, da Silva and Cepko (2017) show
that restricted degradation of retinoic acid and elevated FGF8 signaling give
rise to the chick HAA.
PMID- 28697331
TI - A Tubulin Binding Switch Underlies Kip3/Kinesin-8 Depolymerase Activity.
AB - Kinesin-8 motors regulate the size of microtubule structures, using length
dependent accumulation at the plus end to preferentially disassemble long
microtubules. Despite extensive study, the kinesin-8 depolymerase mechanism
remains under debate. Here, we provide evidence for an alternative, tubulin
curvature-sensing model of microtubule depolymerization by the budding yeast
kinesin-8, Kip3. Kinesin-8/Kip3 uses ATP hydrolysis, like other kinesins, for
stepping on the microtubule lattice, but at the plus end Kip3 undergoes a switch:
its ATPase activity is suppressed when it binds tightly to the curved
conformation of tubulin. This prolongs plus-end binding, stabilizes protofilament
curvature, and ultimately promotes microtubule disassembly. The tubulin curvature
sensing model is supported by our identification of Kip3 structural elements
necessary and sufficient for plus-end binding and depolymerase activity, as well
as by the identification of an alpha-tubulin residue specifically required for
the Kip3-curved tubulin interaction. Together, these findings elucidate a major
regulatory mechanism controlling the size of cellular microtubule structures.
PMID- 28697332
TI - Gating Ciliary Transport.
AB - Cilia lack the ability to synthesize proteins and thus require dynamic transport.
Reporting in this issue of Developmental Cell, Kanie et al. (2017) shed light on
the mechanism of transport by implicating CEP19, which is associated with an
autosomal-recessive obesity syndrome when mutated, in the triggering of
intraflagellar transport.
PMID- 28697334
TI - Heart Regeneration 4.0: Matrix Medicine.
AB - The heart has a markedly limited capacity for regeneration. Reporting in Nature,
Bassat et al. (2017) and Morikawa et al. (2017) have uncovered a new mechanism of
Yap inhibition by the dystrophin glycoprotein complex (DGC) that is released by
the extracellular matrix protein Agrin in order to promote cardiac regeneration.
PMID- 28697333
TI - The DYT6 Dystonia Protein THAP1 Regulates Myelination within the Oligodendrocyte
Lineage.
AB - The childhood-onset motor disorder DYT6 dystonia is caused by loss-of-function
mutations in the transcription factor THAP1, but the neurodevelopmental processes
in which THAP1 participates are unknown. We find that THAP1 is essential for the
timing of myelination initiation during CNS maturation. Conditional deletion of
THAP1 in the CNS retards maturation of the oligodendrocyte (OL) lineage, delaying
myelination and causing persistent motor deficits. The CNS myelination defect
results from a cell-autonomous requirement for THAP1 in the OL lineage and is
recapitulated in developmental assays performed on OL progenitor cells purified
from Thap1 null mice. Loss of THAP1 function disrupts a core set of OL maturation
genes and reduces the DNA occupancy of YY1, a transcription factor required for
OL maturation. These studies establish a role for THAP1 transcriptional
regulation at the inception of myelination and implicate abnormal timing of
myelination in the pathogenesis of childhood-onset dystonia.
PMID- 28697335
TI - Chk1 Inhibition of the Replication Factor Drf1 Guarantees Cell-Cycle Elongation
at the Xenopus laevis Mid-blastula Transition.
AB - The early cell divisions of many metazoan embryos are rapid and occur in the near
absence of transcription. At the mid-blastula transition (MBT), the cell cycle
elongates and several processes become established including the onset of bulk
transcription and cell-cycle checkpoints. How these events are timed and
coordinated is poorly understood. Here we show in Xenopus laevis that
developmental activation of the checkpoint kinase Chk1 at the MBT results in the
SCFbeta-TRCP-dependent degradation of a limiting replication initiation factor
Drf1. Inhibition of Drf1 is the primary mechanism by which Chk1 blocks cell-cycle
progression in the early embryo and is an essential function of Chk1 at the
blastula-to-gastrula stage of development. This study defines the downregulation
of Drf1 as an important mechanism to coordinate the lengthening of the cell cycle
and subsequent developmental processes.
PMID- 28697337
TI - Basement Membrane Manipulation in Drosophila Wing Discs Affects Dpp Retention but
Not Growth Mechanoregulation.
AB - Basement membranes (BMs) are extracellular matrix polymers basally underlying
epithelia, where they regulate cell signaling and tissue mechanics. Constriction
by the BM shapes Drosophila wing discs, a well-characterized model of tissue
growth. Recently, the hypothesis that mechanical factors govern wing growth has
received much attention, but it has not been definitively tested. In this study,
we manipulated BM composition to cause dramatic changes in tissue tension. We
found that increased tissue compression when perlecan was knocked down did not
affect adult wing size. BM elimination, decreasing compression, reduced wing size
but did not visibly affect Hippo signaling, widely postulated to mediate growth
mechanoregulation. BM elimination, in contrast, attenuated signaling by bone
morphogenetic protein/transforming growth factor beta ligand Dpp, which was not
efficiently retained within the tissue and escaped to the body cavity. Our
results challenge mechanoregulation of wing growth, while uncovering a function
of BMs in preserving a growth-promoting tissue environment.
PMID- 28697336
TI - DGAT1-Dependent Lipid Droplet Biogenesis Protects Mitochondrial Function during
Starvation-Induced Autophagy.
AB - Lipid droplets (LDs) provide an "on-demand" source of fatty acids (FAs) that can
be mobilized in response to fluctuations in nutrient abundance. Surprisingly, the
amount of LDs increases during prolonged periods of nutrient deprivation. Why
cells store FAs in LDs during an energy crisis is unknown. Our data demonstrate
that mTORC1-regulated autophagy is necessary and sufficient for starvation
induced LD biogenesis. The ER-resident diacylglycerol acyltransferase 1 (DGAT1)
selectively channels autophagy-liberated FAs into new, clustered LDs that are in
close proximity to mitochondria and are lipolytically degraded. However, LDs are
not required for FA delivery to mitochondria but instead function to prevent
acylcarnitine accumulation and lipotoxic dysregulation of mitochondria. Our data
support a model in which LDs provide a lipid buffering system that sequesters FAs
released during the autophagic degradation of membranous organelles, reducing
lipotoxicity. These findings reveal an unrecognized aspect of the cellular
adaptive response to starvation, mediated by LDs.
PMID- 28697338
TI - HDAC Inhibitors Finally Open Up: Chromatin Accessibility Signatures of CTCL.
AB - In this issue of Cancer Cell, Qu et al. describe the chromatin accessibility
profiles of cutaneous T cell lymphoma, with dynamic assessments of response and
resistance to histone deacetylase inhibitor therapy. Their "personal regulome"
analysis framework reveals chromatin features that may be predictive of clinical
response to epigenetic therapy.
PMID- 28697339
TI - Oncogenic Activation of the RNA Binding Protein NELFE and MYC Signaling in
Hepatocellular Carcinoma.
AB - Global transcriptomic imbalance is a ubiquitous feature associated with cancer,
including hepatocellular carcinoma (HCC). Analyses of 1,225 clinical HCC samples
revealed that a large numbers of RNA binding proteins (RBPs) are dysregulated and
that RBP dysregulation is associated with poor prognosis. We further identified
that oncogenic activation of a top candidate RBP, negative elongation factor E
(NELFE), via somatic copy-number alterations enhanced MYC signaling and promoted
HCC progression. Interestingly, NELFE induces a unique tumor transcriptome by
selectively regulating MYC-associated genes. Thus, our results revealed NELFE as
an oncogenic protein that may contribute to transcriptome imbalance in HCC
through the regulation of MYC signaling.
PMID- 28697340
TI - Stabilization of the c-Myc Protein by CAMKIIgamma Promotes T Cell Lymphoma.
AB - Although high c-Myc protein expression is observed alongside MYC amplification in
some cancers, in most cases protein overexpression occurs in the absence of gene
amplification, e.g., T cell lymphoma (TCL). Here, Ca2+/calmodulin-dependent
protein kinase II gamma (CAMKIIgamma) was shown to stabilize the c-Myc protein by
directly phosphorylating it at serine 62 (S62). Furthermore, CAMKIIgamma was
shown to be essential for tumor maintenance. Inhibition of CAMKIIgamma with a
specific inhibitor destabilized c-Myc and reduced tumor burden. Importantly, high
CAMKIIgamma levels in patient TCL specimens correlate with increased c-Myc and
pS62-c-Myc levels. Together, the CAMKIIgamma:c-Myc axis critically influences the
development and maintenance of TCL and represents a potential therapeutic target
for TCL.
PMID- 28697341
TI - MUC-king with HIF May Rewire Pyrimidine Biosynthesis and Curb Gemcitabine
Resistance in Pancreatic Cancer.
AB - In this issue of Cancer Cell, Singh and colleagues report a role for MUC1-induced
HIF expression in rewiring ribose synthesis, which drives pyridimine production
as a possible resistance mechanism to gemcitabine, adding to complexity and
multiple paths to resistance.
PMID- 28697343
TI - Redefining Hormonal Therapy for Advanced Prostate Cancer: Results from the
LATITUDE and STAMPEDE Studies.
AB - Two papers published recently in the New England Journal of Medicine describe the
utility of abiraterone acetate, an androgen biosynthesis inhibitor, in the early
treatment of metastatic prostate cancer. In addition to establishing a new
standard of care, these two articles pose a number of important questions for
future investigation.
PMID- 28697342
TI - Tumor Evolution of Glioma-Intrinsic Gene Expression Subtypes Associates with
Immunological Changes in the Microenvironment.
AB - We leveraged IDH wild-type glioblastomas, derivative neurospheres, and single
cell gene expression profiles to define three tumor-intrinsic transcriptional
subtypes designated as proneural, mesenchymal, and classical. Transcriptomic
subtype multiplicity correlated with increased intratumoral heterogeneity and
presence of tumor microenvironment. In silico cell sorting identified
macrophages/microglia, CD4+ T lymphocytes, and neutrophils in the glioma
microenvironment. NF1 deficiency resulted in increased tumor-associated
macrophages/microglia infiltration. Longitudinal transcriptome analysis showed
that expression subtype is retained in 55% of cases. Gene signature-based tumor
microenvironment inference revealed a decrease in invading monocytes and a
subtype-dependent increase in macrophages/microglia cells upon disease
recurrence. Hypermutation at diagnosis or at recurrence associated with CD8+ T
cell enrichment. Frequency of M2 macrophages detection associated with short-term
relapse after radiation therapy.
PMID- 28697344
TI - MUC1 and HIF-1alpha Signaling Crosstalk Induces Anabolic Glucose Metabolism to
Impart Gemcitabine Resistance to Pancreatic Cancer.
AB - Poor response to cancer therapy due to resistance remains a clinical challenge.
The present study establishes a widely prevalent mechanism of resistance to
gemcitabine in pancreatic cancer, whereby increased glycolytic flux leads to
glucose addiction in cancer cells and a corresponding increase in pyrimidine
biosynthesis to enhance the intrinsic levels of deoxycytidine triphosphate
(dCTP). Increased levels of dCTP diminish the effective levels of gemcitabine
through molecular competition. We also demonstrate that MUC1-regulated
stabilization of hypoxia inducible factor-1alpha (HIF-1alpha) mediates such
metabolic reprogramming. Targeting HIF-1alpha or de novo pyrimidine biosynthesis,
in combination with gemcitabine, strongly diminishes tumor burden. Finally,
reduced expression of TKT and CTPS, which regulate flux into pyrimidine
biosynthesis, correlates with better prognosis in pancreatic cancer patients on
fluoropyrimidine analogs.
PMID- 28697346
TI - [Necrozoospermia: From etiologic diagnosis to therapeutic management].
AB - This review describes necrospermia, its diagnosis, causes and management. Sperm
vitality is commonly assessed in the laboratory of reproductive biology, with the
eosin test or with the hypo-osmotic swelling test. Necrospermia is defined by a
percentage of living spermatozoa inferior to 58%, and can be related to male
infertility. Several pathological mechanisms may be involved and can be
classified either in testicular causes (hyperthyroidism, local hyperthermia,
varicocele), or post-testicular causes (epididymal necrospermia, dysregulation of
seminal plasma, adult polycystic kidney disease, vasectomy reversal, anti-sperm
antibodies) or both (infection, toxic, age, spinal cord injury). The first
treatment is to correct the underlying cause, if possible. Repetitive ejaculation
has demonstrated to be effective as well. Many drugs would also improve the sperm
vitality (antioxidants, non-and-steroidal anti-inflammatory drugs) but there is
currently no guideline to recommend their use. With necrospermia, fertilization
rates are lower but in vitro fertilization (IVF) with Intracytoplasmic sperm
injection (ICSI) improves the chances of conception.
PMID- 28697347
TI - Immediate Reconstruction and Dental Rehabilitation of Segmental Mandibular
Defects: Description of a Novel Technique.
AB - The aim of this report is to present a new technique using current technologic
advances for immediate reconstruction and dental rehabilitation of segmental
mandibular defects with a screw-retained prosthesis. One case is reviewed and a
detailed review of surgical and prosthetic techniques used is presented.
PMID- 28697345
TI - Choose and Use Your Chemical Probe Wisely to Explore Cancer Biology.
AB - Small-molecule chemical probes or tools have become progressively more important
in recent years as valuable reagents to investigate fundamental biological
mechanisms and processes causing disease, including cancer. Chemical probes have
also achieved greater prominence alongside complementary biological reagents for
target validation in drug discovery. However, there is evidence of widespread
continuing misuse and promulgation of poor-quality and insufficiently selective
chemical probes, perpetuating a worrisome and misleading pollution of the
scientific literature. We discuss current challenges with the selection and use
of chemical probes, and suggest how biologists can and should be more
discriminating in the probes they employ.
PMID- 28697348
TI - In Reply.
PMID- 28697349
TI - Styloid Process Fracture Associated With Maxillofacial Trauma: Incidence,
Distribution, and Management.
AB - PURPOSE: Fracture of the styloid process of the temporal bone has been
infrequently reported. The present study evaluated the incidence, causes,
distribution, and management of styloid process fracture in association with
other maxillofacial fractures. MATERIALS AND METHODS: A prospective evaluation of
patients with maxillofacial trauma over a period of 1 year was carried out and
patients' characteristics, mode and distribution of injury, and length of styloid
process were recorded. Patients were divided into 5 groups based on the site of
maxillofacial fracture and into 2 groups based on styloid process length to
evaluate their association with styloid process fracture. The authors' unit
protocol was carried out for management of styloid process fracture. RESULTS: Of
84 patients with maxillofacial trauma, 27 patients (14 men, 13 women; mean age,
25.7 +/- 8.92 yr) had styloid process fracture. The most common cause of injury
was road traffic accidents. Mandibular and multiple facial fractures accounted
for most concomitant styloid process fractures. The mean length of the styloid
process in patients with fracture was 2.46 +/- 0.89 cm and no relevant
association was present between the length and fracture of the styloid process.
All patients responded well to initial conservative management. CONCLUSION:
Styloid process fractures are relatively common injuries in developing countries
and a meticulous examination is essential for prompt diagnosis and adequate care.
PMID- 28697350
TI - Extended Karapandzic Flap Technique for Reconstruction of Lower Lip and Chin
Defect.
AB - PURPOSE: Near total defect of the lower lip adjacent to the chin remains a
reconstructive challenge for surgeons in function and esthetics. The objective of
this study was to present a modified extended Karapandzic technique for
reconstruction of near total defects of the lower lip adjacent with the chin.
MATERIALS AND METHODS: From 2000 to 2013, patients with lip cancer or oral cavity
cancer who required subtotal lower lip and chin resection and subsequently
underwent reconstruction with an extended Karapandzic flap were included in this
retrospective study. Patient demographics, histopathology, tumor stage,
localization, tumor extension, method of reconstruction, and postoperative
complications were extracted from patients' documentation. RESULTS:
Reconstruction of the lower lip and chin was performed in 21 patients using a
combination of double local extended Karapandzic flaps with microvascular free
flaps for intraoral and mandibular reconstruction. There was no flap necrosis;
the main complications were fistula and exposure of the osteosynthesis plate. All
lips were functional and the esthetic result was pleasing. All patients returned
to a peroral diet, although a variable degree of microstomia was present.
CONCLUSION: The extended Karapandzic flap technique provides superior results for
esthetic and functional lip reconstruction and chin reconstruction compared with
any other regional or free flap. Free flaps should be reserved for oral cavity
and mandibular reconstruction, if needed.
PMID- 28697351
TI - Desai et al on Multiple Calcifying Hyperplastic Dental Follicles: A Critique.
PMID- 28697352
TI - In Response to "Routine Postoperative Imaging Is Not Indicated in the Management
of Mandibular Fractures".
PMID- 28697353
TI - Marine Biodiversity, Biogeography, Deep-Sea Gradients, and Conservation.
PMID- 28697354
TI - The Human Fetus Preferentially Engages with Face-like Visual Stimuli.
PMID- 28697355
TI - Prohibitins.
AB - Tatsuta and Langer introduce prohibitins, membrane scaffolding proteins found
predominantly in mitochondria.
PMID- 28697356
TI - Perceptual learning.
AB - Perceptual learning refers to how experience can change the way we perceive
sights, sounds, smells, tastes, and touch. Examples abound: music training
improves our ability to discern tones; experience with food and wines can refine
our pallet (and unfortunately more quickly empty our wallet), and with years of
training radiologists learn to save lives by discerning subtle details of images
that escape the notice of untrained viewers. We often take perceptual learning
for granted, but it has a profound impact on how we perceive the world. In this
Primer, I will explain how perceptual learning is transformative in guiding our
perceptual processes, how research into perceptual learning provides insight into
fundamental mechanisms of learning and brain processes, and how knowledge of
perceptual learning can be used to develop more effective training approaches for
those requiring expert perceptual skills or those in need of perceptual
rehabilitation (such as individuals with poor vision). I will make a case that
perceptual learning is ubiquitous, scientifically interesting, and has
substantial practical utility to us all.
PMID- 28697357
TI - A hydrodynamically active flipper-stroke in humpback whales.
AB - A central paradigm of aquatic locomotion is that cetaceans use fluke strokes to
power their swimming while relying on lift and torque generated by the flippers
to perform maneuvers such as rolls, pitch changes and turns [1]. Compared to
other cetaceans, humpback whales (Megaptera novaeangliae) have disproportionately
large flippers with added structural features to aid in hydrodynamic performance
[2,3]. Humpbacks use acrobatic lunging maneuvers to attack dense aggregations of
krill or small fish, and their large flippers are thought to increase their
maneuverability and thus their ability to capture prey. Immediately before
opening their mouths, humpbacks will often rapidly move their flippers, and it
has been hypothesized that this movement is used to corral prey [4,5] or to
generate an upward pitching moment to counteract the torque caused by rapid water
engulfment [6]. Here, we demonstrate an additional function for the rapid flipper
movement during lunge feeding: the flippers are flapped using a complex,
hydrodynamically active stroke to generate lift and increase propulsive thrust.
We estimate that humpback flipper-strokes are capable of producing large forward
oriented forces, which may be used to enhance lunge feeding performance. This
behavior is the first observation of a lift-generating flipper-stroke for
propulsion cetaceans and provides an additional function for the uniquely shaped
humpback whale flipper.
PMID- 28697358
TI - Respiratory gut peristalsis by sea spiders.
AB - The fundamental constraint shaping animal systems for internal gas transport is
the slow pace of diffusion [1]. In response, most macroscopic animals have
evolved systems for driving internal flows using muscular pumps or cilia. In
arthropods, aside from terrestrial lineages that exchange gases via tracheal
systems, most taxa have a dorsal heart that drives O2-carrying hemolymph through
peripheral vessels and an open hemocoel [2], with O2 often bound to respiratory
proteins. Here we show that pycnogonids (sea spiders), a basal group of marine
arthropods [3], use a previously undescribed mechanism of internal O2 transport:
flows of gut fluids and hemolymph driven by peristaltic contractions of a space
filling system of gut diverticula. This observation fundamentally expands the
known range of gas-transport systems in extant arthropods.
PMID- 28697359
TI - Male reproductive skew is higher in bonobos than chimpanzees.
AB - The two closest living relatives of humans, bonobos (Pan paniscus) and
chimpanzees (Pan troglodytes), share many traits that are common in humans but
rare in other mammals, including societies with high fission-fusion dynamics,
male philopatry, female dispersal and extensive social bonding among unrelated
individuals [1]. The major difference between these two species is that male
aggression is more frequent and intense in male-dominated chimpanzees than in
bonobos, where the highest-ranking individuals are female [1]. One potential
explanation is that because periods of female sexual receptivity and
attractiveness are more extended in bonobos [2], males compete less intensely for
each mating opportunity. This would reduce the strength of selection for traits
that lead to success in direct contest competition between males and in sexual
coercion of females, thus increasing the potential for female choice [3].
Accordingly, it has been predicted that the influence of male dominance rank on
reproductive success and the extent of male reproductive skew should be lower in
bonobos than in chimpanzees [1]. Although relevant for understanding the
evolution of the unusual levels of egalitarianism and cooperation found in human
hunter-gatherers [4], comparative analyses in the genus Pan have been limited by
the scanty paternity data available for wild bonobos [5]. Here, we show using the
largest sample of paternity data available that, contrary to expectation, male
bonobos have a higher reproductive skew and a stronger relationship between
dominance rank and reproductive success than chimpanzees.
PMID- 28697360
TI - Host-Microbe Interactions: Winning the Colonization Lottery.
AB - Stochastic bottlenecks during bacterial colonization of animal hosts lead to
reduced genetic diversity in the resulting microbiota and, at low-inoculation
doses, can result in hosts that remain uncolonized. Bacterial strains vary in
their colonization efficiency and resistance to displacement.
PMID- 28697361
TI - Vision: Melanopsin as a Raumgeber.
AB - Two new studies show that neural systems receiving inputs from the melanopsin
containing retinal ganglion cells encode spatial information and therefore see
the world in more detail than previously thought.
PMID- 28697362
TI - Evolution: Gene Co-option Underpins Venom Protein Evolution.
AB - Venoms contain variable mixtures of bioactive proteins. New work shows that
parasitoid wasp venom toxins evolve by the co-option of genes rather than the
canonical process of gene duplication. These findings suggest co-option may be an
underappreciated process underpinning protein neofunctionalization.
PMID- 28697363
TI - Spatial Navigation: Retrosplenial Cortex Encodes the Spatial Structure of Complex
Routes.
AB - A new study in which recordings were made from the retrosplenial cortex while
rats navigated through a complex environment has revealed populations of cells
that encode route-segments as well as the relative position of these segments
within an allocentric framework.
PMID- 28697364
TI - Evolution: King-Size Plastid Genomes in a New Red Algal Clade.
AB - Plastids, the photosynthetic organelles of eukaryotes, exhibit remarkably stable
genome architecture. However, a recent study of microscopic red algae has found
new record-sized plastid genomes with unusual architectures. These species form a
new branch in the tree of red algae.
PMID- 28697365
TI - Sensory Cilia: Generating Diverse Shapes One Ig Domain at a Time.
AB - How morphologically complex cilia form is not well understood. A key regulator of
ciliary shape has now been identified that links the establishment of neuronal
fate with the formation of cell-specific ciliary structures in Caenorhabditis
elegans.
PMID- 28697366
TI - Circadian Biology: Uncoupling Human Body Clocks by Food Timing.
AB - Synchrony of circadian rhythms between tissues/organs appears critical for
health. A new study reports that meal timing, a modifiable temporal cue for the
circadian system, can selectively uncouple circadian rhythms in metabolic
physiology from the central circadian clock in humans.
PMID- 28697367
TI - Meiotic Sex Chromosome Inactivation: Compensation by Gene Traffic.
AB - It has been widely observed that sex-related genes are copied from sex
chromosomes and inserted into autosomes, a process termed 'gene traffic'.
However, the adaptive significance of this phenomenon is unclear. Now, direct
evidence has been provided that gene traffic may allow functional compensation
during meiotic sex chromosome activation.
PMID- 28697368
TI - Gene Evolution: Getting Something from Nothing.
AB - New genes arise from pre-existing genes, but some de novo origin from non-genic
sequence also seems plausible. A new study has surprisingly concluded that 25% of
random DNA sequences yield beneficial products when expressed in bacteria.
PMID- 28697369
TI - Endocytosis: Remote Control from Deep Inside.
AB - The endoplasmic reticulum communicates directly through membrane contacts with
other cellular organelles. A new study reports that the formation and detachment
of endocytic uptake carriers for the clathrin-independent internalization of the
epidermal growth factor receptor is dependent on such contact sites.
PMID- 28697370
TI - The Evolution of Calcium-Based Signalling in Plants.
AB - The calcium-based intracellular signalling system is used ubiquitously to couple
extracellular stimuli to their characteristic intracellular responses. It is
becoming clear from genomic and physiological investigations that while the basic
elements in the toolkit are common between plants and animals, evolution has
acted in such a way that, in plants, some components have diversified with
respect to their animal counterparts, while others have either been lost or have
never evolved in the plant lineages. In comparison with animals, in plants there
appears to have been a loss of diversity in calcium-influx mechanisms at the
plasma membrane. However, the evolution of the calcium-storing vacuole may
provide plants with additional possibilities for regulating calcium influx into
the cytosol. Among the proteins that are involved in sensing and responding to
increases in calcium, plants possess specific decoder proteins that are absent
from the animal lineage. In seeking to understand the selection pressures that
shaped the plant calcium-signalling toolkit, we consider the evolution of fast
electrical signalling. We also note that, in contrast to animals, plants
apparently do not make extensive use of cyclic-nucleotide-based signalling. It is
possible that reliance on a single intracellular second-messenger-based system,
coupled with the requirement to adapt to changing environmental conditions, has
helped to define the diversity of components found in the extant plant calcium
signalling toolkit.
PMID- 28697371
TI - Dendrimer nanohybrid carrier systems: an expanding horizon for targeted drug and
gene delivery.
AB - Highly controllable dendritic structural design means dendrimers are a leading
carrier in drug delivery applications. Dendrimer- and other nanocarrier-based
hybrid systems are an emerging platform in the field of drug delivery. This
review is a compilation of increasing reports of dendrimer interactions, such as
dendrimer-liposome, dendrimer-carbon-nanotube, among others, known as hybrid
carriers. This should prompt entirely new research with promising results for
these hybrid carriers. It is assumed that such emerging hybrid nanosystems - from
combining two already-established drug delivery platforms - could lead the way
for the development of newer delivery systems with multiple applicability for
latent theranostic applications in the future.
PMID- 28697372
TI - History, politics and vulnerability: explaining excess mortality in Scotland and
Glasgow.
AB - OBJECTIVES: High levels of excess mortality (i.e. that not explained by
deprivation) have been observed for Scotland compared with England & Wales, and
especially for Glasgow in comparison with similar post-industrial cities such as
Liverpool and Manchester. Many potential explanations have been suggested. Based
on an assessment of these, the aim was to develop an understanding of the most
likely underlying causes. Note that this paper distils a larger research report,
with the aim of reaching wider audiences beyond Scotland, as the important
lessons learnt are relevant to other populations. STUDY DESIGN: Review and
dialectical synthesis of evidence. METHODS: Forty hypotheses were examined,
including those identified from a systematic review. The relevance of each was
assessed by means of Bradford Hill's criteria for causality alongside-for
hypotheses deemed causally linked to mortality-comparisons of exposures between
Glasgow and Liverpool/Manchester, and between Scotland and the rest of Great
Britain. Where gaps in the evidence base were identified, new research was
undertaken. Causal chains of relevant hypotheses were created, each tested in
terms of its ability to explain the many different aspects of excess mortality.
The models were further tested with key informants from public health and other
disciplines. RESULTS: In Glasgow's case, the city was made more vulnerable to
important socioeconomic (deprivation, deindustrialisation) and political
(detrimental economic and social policies) exposures, resulting in worse
outcomes. This vulnerability was generated by a series of historical factors,
processes and decisions: the lagged effects of historical overcrowding; post-war
regional policy including the socially selective relocation of population to
outside the city; more detrimental processes of urban change which impacted on
living conditions; and differences in local government responses to UK government
policy in the 1980s which both impacted in negative terms in Glasgow and also
conferred protective effects on comparator cities. Further resulting protective
factors were identified (e.g. greater 'social capital' in Liverpool) which placed
Glasgow at a further relative disadvantage. Other contributory factors were
highlighted, including the inadequate measurement of deprivation. A similar
'explanatory model' resulted for Scotland as a whole. This included: the
components of the Glasgow model, given their impact on nationally measured
outcomes; inadequate measurement of deprivation; the lagged effects of
deprivation (in particular higher levels of overcrowding historically); and
additional key vulnerabilities. CONCLUSIONS: The work has helped to further
understanding of the underlying causes of Glasgow's and Scotland's high levels of
excess mortality. The implications for policy include the need to address three
issues simultaneously: to protect against key exposures (e.g. poverty) which
impact detrimentally across all parts of the UK; to address the existing
consequences of Glasgow's and Scotland's vulnerability; and to mitigate against
the effects of future vulnerabilities which are likely to emerge from policy
responses to contemporary problems which fail sufficiently to consider and to
prevent long-term, unintended social consequences.
PMID- 28697373
TI - Rural-urban differences in receiving guideline-recommended diabetes care and
experiencing avoidable hospitalizations under a universal coverage health system:
evidence from the past decade.
AB - OBJECTIVES: Rural-urban differences in health remain a concern worldwide. Few
studies have investigated the dynamic changes in health between rural and urban
areas. This study aims to examine whether the rural-urban gap in patients'
receipt of guideline-recommended care and avoidable hospitalizations has
decreased in 10 years under a universal coverage health system. STUDY DESIGN: A
retrospective cohort study design. METHODS: This study utilized nationwide health
insurance claims data of 3 representative cohorts of patients with newly
diagnosed type 2 diabetes in 2000, 2005, and 2010 in Taiwan. The two outcome
variables were receipt of guideline-recommended care and avoidable
hospitalizations for diabetes. Generalized estimating equations models were used
to estimate the rural-urban differences while controlling for physician
clustering effects. RESULTS: Rural diabetic patients were less likely to receive
guideline-recommended examinations/tests in 2000 (ebeta = 0.97; 95% confidence
interval [CI]: 0.96-0.99); however, the average number of examinations/tests
increased and the rural-urban difference had diminished in 2010. The likelihood
of avoidable hospitalizations for diabetes among rural diabetic patients was
higher than that for their urban counterparts in 2000 (odds ratio [OR]: 1.13; 95%
CI: 1.01-1.25). Although the likelihood of avoidable hospitalizations for
diabetes decreased from 2000 to 2010, the rural-urban gap remained during this
period. CONCLUSIONS: The rural-urban disparity in receiving recommended diabetes
care diminished over the past decade. However, significant gaps between rural and
urban areas in avoidable hospitalizations for diabetes persisted despite the
universal health system.
PMID- 28697374
TI - Counselor competence for telephone Motivation Interviewing addressing lifestyle
change among Dutch older adults.
AB - Counselor competence in telephone Motivation Interviewing (MI) to change
lifestyle behaviors in a primary care population was assessed using the
Motivational Interviewing Treatment Integrity (MITI) rating system. Counselor
behavior was evaluated by trained raters. Twenty minutes of a random sample of
336 MI sessions were coded representing 232 counselees. Ninety-four sessions
(28%) were double coded to assess inter-rater agreement. The MI fidelity was
examined by comparing the MI fidelity scores direction, empathy, spirit, % open
questions, % complex reflections, reflections-to-questions ratio, % MI-adherent
responses with the matching beginner proficiency MITI threshold. The inter-rater
agreements for the MI fidelity summary scores were good (spirit, reflections-to
questions ratio), fair (empathy, % open questions, % MI-adherent responses) or
poor (direction, % complex reflection). The MI fidelity scores for direction,
empathy, spirit and the percentage of complex reflections exceeded the MITI
threshold, but lower scores were found for the percentage of open questions, the
reflections-to-questions ratio and the percentage of MI-adherent responses. In
conclusion, evidence that MI was implemented was revealed. However, the inter
rater agreements scores and some fidelity scores leave room for improvement
indicating that raters and counselors may need more ongoing training and feedback
to achieve and maintain adequate competence. These findings apply to more complex
skills (as rating complex reflections) in particular.
PMID- 28697375
TI - Interhemispheric cortical connections and time perception: A case study with
agenesis of the corpus callosum.
AB - In daily life, we sometimes select temporal cues of one sort while suppressing
others. This study investigated the mechanism of suppression by examining a split
brain patient's perception of target intervals while ignoring distractor
intervals. A patient with agenesis of corpus callosum and five age- and sex
matched control subjects participated in reproduction of target intervals while
ignoring distractors displayed in the visual field either ipsilateral or
contralateral to target. In the patient, the distractor interfered with
reproduction performance more strongly when contralateral rather than
ipsilateral. Our results suggest that the corpus callosum plays an inhibitory
role in interhemispheric interference and that temporal interval information can
be transferred via subcortical structures when there are no direct
interhemispheric pathways.
PMID- 28697376
TI - ERPs and oscillations during encoding predict retrieval of digit memory in
superior mnemonists.
AB - Previous studies have consistently demonstrated that superior mnemonists (SMs)
outperform normal individuals in domain-specific memory tasks. However, the
neural correlates of memory-related processes remain unclear. In the current EEG
study, SMs and control participants performed a digit memory task during which
their brain activity was recorded. Chinese SMs used a digit-image mnemonic for
encoding digits, in which they associated 2-digit groups with images immediately
after the presentation of each even-position digit in sequences. Behaviorally,
SMs' memory of digit sequences was better than the controls'. During encoding in
the study phase, SMs showed an increased right central P2 (150-250ms post onset)
and a larger right posterior high-alpha (10-14Hz, 500-1720ms) oscillation on
digits at even-positions compared with digits at odd-positions. Both P2 and high
alpha oscillations in the study phase co-varied with performance in the recall
phase, but only in SMs, indicating that neural dynamics during encoding could
predict successful retrieval of digit memory in SMs. Our findings suggest that
representation of a digit sequence in SMs using mnemonics may recruit both the
early-stage attention allocation process and the sustained information
preservation process. This study provides evidence for the role of dynamic and
efficient neural encoding processes in mnemonists.
PMID- 28697377
TI - Absence of regulator of G-protein signaling 4 does not protect against dopamine
neuron dysfunction and injury in the mouse 6-hydroxydopamine lesion model of
Parkinson's disease.
AB - Regulator of G-protein signaling 4 (RGS4), a member of the RGS family of proteins
that inactivate G-proteins, has gained interest as a potential drug target for
neurological disorders, such as epilepsy and Parkinson's disease (PD). In the
case of PD, the main current options for alleviating motor symptoms are dopamine
replacement therapies, which have limitations because of side effects and reduced
effectiveness over the long term. Research on new nondopaminergic PD drug targets
has indicated that inhibition of RGS4 could be an effective adjuvant treatment
option. The effectiveness of RGS4 inhibition for an array of PD-linked functional
and structural neuroprotection end points has not yet been demonstrated. Here, we
use the 6-hydroxydopamine (6-OHDA) lesioning model of the nigrostriatal pathway
in mice to address this question. We observe, using a battery of behavioral and
pathological measures, that mice deficient for RGS4 are not protected from 6-OHDA
induced injury and show enhanced susceptibility in some measures of motor
function. Our results suggest that inhibition of RGS4 as a nondopaminergic target
for PD should be approached with caution.
PMID- 28697378
TI - Changes in phagocytosis and potassium channel activity in microglia of 5xFAD mice
indicate alterations in purinergic signaling in a mouse model of Alzheimer's
disease.
AB - As the immunocompetent cells of the central nervous system, microglia accumulate
at amyloid beta plaques in Alzheimer's disease (AD) and acquire a morphological
phenotype of activated microglia. Recent functional studies, however, indicate
that in mouse models of amyloidosis and AD, these cells are rather dysfunctional
indicated by a reduced phagocytic activity. Here, we report that this reduction
in phagocytic activity is associated with perturbed purinergic receptor
signaling, since phagocytosis could be stimulated by P2Y6 receptor activation in
control, but not in 5xFAD transgenic animals, an animal model of amyloid
deposition. Impaired phagocytosis is not innate, and develops only at later
stages of amyloidosis. Furthermore, we show that membrane currents induced by
uridine diphosphate, a ligand activating P2Y6 receptors, are altered in response
rate and amplitude in microglia in close vicinity to plaques, but not in plaque
free areas of 5xFAD animals. These changes were accompanied by changes in
membrane properties and potassium channel activity of plaque-associated microglia
in early and late stages of amyloidosis. As a conclusion, the physiological
properties of plaque-associated microglia are altered with a strong impact on
purinergic signaling.
PMID- 28697379
TI - Efficacy and evaluation of environmental management system to control sandfly
vector of Kala-azar.
AB - The established vector for visceral leishmaniasis, Phlebotomus argentipes
(Diptera: Psychodidae) breeds inside the human dwellings and cattle shed under
crevices at the base of the wall. P. argentipes was controlled by plastering the
base of wall (9"height * 9"base). The study was conducted in two phases: (i)
Screening of plastering materials (ii) validation of the most suitable material.
During the first phase (2014); four intervention materials were evaluated in four
different arms: (i) cement (ii) brick chimney fly ash (BCFA i.e. waste material
from an oven for backing raw earthen brick in charcoal) mixed with lime (95:5)
(iii) wire mesh (25 holes/cm2) and (iv) glazed tiles. Ten houses were selected as
test and same as control in four different villages for each arm having similar
ecotype and similar density of sandflies. The pre and post intervention density
of sandflies were evaluated. Significant reduction in sandfly density was found
with cement (46.2%) and BCFA (29.6%) plastering (P < 0.05). In the second phase
of the study (2015); the two most effective interventions were validated at
village level with one control. A significant reduction in the density of P.
argentipes was found with cement; 60.2% (Mean +/- S.D. = 2.48 +/- 2.78, 95% CI =
1.93-3.02) and BCFA; 48.2% (Mean +/- S.D. = 1.98 +/- 2.20, 95% CI = 1.55-2.41) (P
< 0.05). BCFA was found easily accessible, acceptable and cost effective that can
be used in any type of wall materials at own cost. This can be implemented as one
of the integrated vector control approach in the programme.
PMID- 28697380
TI - Assessment of carbon sequestration potential of revegetated coal mine overburden
dumps: A chronosequence study from dry tropical climate.
AB - Development of secondary forest as post-mining land use in the surface coal
mining degraded sites is of high research interest due to its potential to
sequester atmospheric carbon (C). The objectives of this study were to assess the
improvement in mine soil quality and C sequestration potential of the post-mining
reclaimed land with time. Hence, this study was conducted in reclaimed
chronosequence sites (young, intermediate and old) of a large open cast coal
project (Central Coal Fields Limited, Jharkhand, India) and results were compared
to a reference forest site (Sal forest, Shorea robusta). Mine soil quality was
assessed in terms of accretion of soil organic carbon (SOC), available nitrogen
(N) and soil CO2 flux along with the age of revegetation. After 14 years of
revegetation, SOC and N concentrations increased three and five-fold,
respectively and found equivalent to the reference site. Accretion of SOC stock
was estimated to be 1.9 Mg C ha-1year-1. Total ecosystem C sequestered after 2-14
years of revegetation increased from 8 Mg C ha-1 to 90 Mg C ha-1 (30-333 Mg CO2
ha-1) with an average rate of 6.4 Mg C ha-1year-1. Above ground biomass
contributes maximum C sequestrate (50%) in revegetated site. CO2 flux increased
with age of revegetation and found 11, 33 and 42 Mg CO2 ha-1year-1 in younger,
intermediate and older dumps, respectively. Soil respiration in revegetated site
is more influenced by the temperature than soil moisture. Results of the study
also showed that trees like, Dalbergia sissoo and Heterophragma adenophyllum
should be preferred for revegetation of mine degraded sites.
PMID- 28697381
TI - Evaluation of activated carbon fiber supported nanoscale zero-valent iron for
chromium (VI) removal from groundwater in a permeable reactive column.
AB - An activated carbon fiber supported nanoscale zero-valent iron (ACF-nZVI)
composite for Cr(VI) removal from groundwater was synthesized according to the
liquid phase reduction method. The techniques of N2 adsorption/desorption, FESEM,
EDX, XRD and XPS were used to characterize the ACF-nZVI composite and the
interaction between the ACF-nZVI composite and Cr(VI) ions. Batch experiments
were conducted to evaluate the effects of several factors, including the amount
of nZVI on activated carbon fiber (ACF), pH value, initial Cr(VI) concentration,
and co-existing ions on Cr(VI) removal. The results indicate that presence of ACF
can inhibit the aggregation of nanoscale zero-valent iron (nZVI) particles and
increase its reactivity, and the Cr(VI) removal efficiency increases with
increasing amounts of nZVI on ACF and a decrease in the initial Cr(VI)
concentration. In acidic conditions, almost 100% of Cr(VI) in solution can be
removed after 60 min of reaction, and the removal efficiency decreases with
increasing initial pH values. The Cr(VI) removal is also dependent on the co
existing ions. Reusability experiments on ACF-nZVI demonstrate that the ACF-nZVI
composite can keep a high reactivity after five successive reduction cycles. The
removal mechanisms are proposed as a two-step interaction including the physical
adsorption of Cr(VI) on the surface or inner layers of the ACF-nZVI composite and
the subsequent reduction of Cr(VI) to Cr(III) by nZVI.
PMID- 28697382
TI - Bacterial mobilization and transport through manure enriched soils: Experiment
and modeling.
AB - A precise evaluation of bacteria transport and mathematical investigations are
useful for best management practices in agroecosystems. In this study, using
laboratory experiments and modeling approaches, we assess the transport of
bacteria released from three types of manure (cow, sheep, and poultry) to find
the importance of the common manures in agricultural activities in soil and water
pollution. Thirty six intact soil columns with different textures (sandy, loamy,
and silty clay loam) were sampled. Fecal coliform leaching from layers of the
manures on the soil surface was conducted under steady-state saturated flow
conditions at 20 degrees C for up to four Pore Volumes (PVs). Separate leaching
experiments were conducted to obtain the initial concentrations of bacteria
released from the manures (Co). Influent (Co) and effluent (C) bacteria
concentrations were measured by the plate-count method and the normalized
concentrations (C/C0) were plotted versus PV representing the breakthrough curves
(BTCs). Transport parameters were predicted using the attachment/detachment model
(two-kinetic site) in HYDRUS-1D. Simulations fitted well the experimental data
(R2 = 0.50-0.96). The attachment, detachment, and straining coefficients of
bacteria were more influenced by the soils treated with cow manure compared to
the sheep and poultry manures. Influent curves of fecal coliforms from the
manures (leached without soil) illustrated that the poultry manure had the
highest potential to pollute the effluent water from the soils in term of
concentration, but the BTCs and simulated data related to the treated soils
illustrated that the physical shape of cow manure was more important to both
straining and detachment of bacteria back into the soil solution. Detachment
trends of bacteria were observed through loam and silty clay loam soils treated
with cow manure compared to the cow manure enriched sandy soil. We conclude that
management strategies must specifically minimize the effect of fecal coliform
concentrations before field application, especially for the combination of
poultry and cow manures, which has higher solubility and tailing behavior,
respectively. Interestingly, the addition of sheep manure with all three soils
had the lowest mobilization of bacteria. We also suggest studying the chemistry
of soil solution affected by manures to present all relevant information which
affect bacterial movement through soils during leaching.
PMID- 28697383
TI - On the loss of information in PCA of spectrum-images.
AB - Principal Component Analysis (PCA) can drastically denoise STEM spectrum-images
but might distort or cut off the important variations in data. The present paper
analyzes various approaches to estimate such deviations and compares them with
the simulated data. A spiked covariance model by Nadler (2008) appears to be most
appropriated for application in STEM spectrum-imaging.
PMID- 28697384
TI - Schizosaccharomyces pombe and Saccharomyces cerevisiae yeasts in sequential
fermentations: Effect on phenolic acids of fermented Kei-apple (Dovyalis caffra
L.) juice.
AB - Kei-apple (Dovyalis caffra) is an evergreen tree indigenous to Southern Africa.
The fruit contains high concentrations of l-malic acid, ascorbic acid, and
phenolic acids. Kei-apple juice was sequentially inoculated with
Schizosaccharomyces pombe and Saccharomyces cerevisiae yeasts. A reference
fermentation using only S. cerevisiae was included. The fermentation was
monitored by recording mass loss. At the end of fermentation, twelve untrained
judges conducted free choice aroma profiling on the fruit wines. The Kei-apple
juice and wines were analysed for total titratable acidity, total soluble solids,
pH, alcohol, l-malic acid, and phenolic acids. Total titratable acidity was ca.
70% lower in Kei-apple wines produced with S. pombe+S. cerevisiae than in Kei
apple juice. Kei-apple wines produced with S. pombe+S. cerevisiae showed
substantially lower concentrations of l-malic acid than Kei-apple wines produced
with S. cerevisiae only. Wines produced with S. cerevisiae only proved higher in
phenolic acid concentrations than wines produced with S. pombe+S. cerevisiae.
Chlorogenic acid was the most abundant phenolic acid measured in the Kei-apple
wines, followed by protocatechuic acid. Judges described the Kei-apple wines
produced with S. pombe+S. cerevisiae as having noticeable off-odours, while wines
produced with S. cerevisiae were described as fresh and fruity. Kei-apple wines
(S. pombe+S. cerevisiae and S. cerevisiae) were of comparable vegetative and
organic character. Saccharomyces cerevisiae produced Kei-apple wine with
increased caffeic, chlorogenic, protocatechuic, and sinapic acids, whereas S.
pombe+S. cerevisiae produced Kei-apple wines with increased ferulic, and p
coumaric acids and low l-malic acid.
PMID- 28697385
TI - Quantitative contamination assessment of Escherichia coli in baby spinach primary
production in Spain: Effects of weather conditions and agricultural practices.
AB - A quantitative microbial contamination model of Escherichia coli during primary
production of baby spinach was developed. The model included only systematic
contamination routes (e.g. soil and irrigation water) and it was used to evaluate
the potential impact of weather conditions, agricultural practices as well as
bacterial fitness in soil on the E. coli levels present in the crop at harvest.
The model can be used to estimate E. coli contamination of baby spinach via
irrigation water, via soil splashing due to irrigation water or rain events, and
also including the inactivation of E. coli on plants due to solar radiation
during a variable time of culturing before harvest. Seasonality, solar radiation
and rainfall were predicted to have an important impact on the E. coli
contamination. Winter conditions increased E. coli prevalence and levels when
compared to spring conditions. As regards agricultural practices, both water
quality and irrigation system slightly influenced E. coli levels on baby spinach.
The good microbiological quality of the irrigation water (average E. coli counts
in positive water samples below 1 log/100mL) could have influenced the
differences observed among the tested agricultural practices (water treatment and
irrigation system). This quantitative microbial contamination model represents a
preliminary framework that assesses the potential impact of different factors and
intervention strategies affecting E. coli concentrations at field level. Taking
into account that E. coli strains may serve as a surrogate organism for enteric
bacterial pathogens, obtained results on E. coli levels on baby spinach may be
indicative of the potential behaviour of these pathogens under defined
conditions.
PMID- 28697386
TI - Alterations in functional brain networks associated with loss-chasing in gambling
disorder and cocaine-use disorder.
AB - BACKGROUND: Continued, persistent gambling to recover accumulating losses, or
'loss-chasing', is a behavioral pattern linked particularly closely to gambling
disorder (GD) but may reflect impaired decision-making processes relevant to drug
addictions like cocaine-use disorder (CUD). However, little is known regarding
the neurocognitive mechanisms of this complex, maladaptive behavior, particularly
in individuals with addictive disorders. METHODS: Seventy participants (25 GD, 18
CUD, and 27 healthy comparison (HC)) completed a loss-chase task during fMRI.
Engagement of functional brain networks in response to losing outcomes and during
decision-making periods preceding choices to loss-chase or to quit chasing losses
were investigated using independent component analysis (ICA). An exploratory
factor analysis was performed to examine patterns of coordinated engagement
across identified networks. RESULTS: In GD relative to HC and CUD participants,
choices to quit chasing were associated with greater engagement of a medial
frontal executive-processing network. By comparison, CUD participants exhibited
altered engagement of a striato-amygdala motivational network in response to
losing outcomes as compared to HC, and during decision-making as compared to GD.
Several other networks were differentially engaged during loss-chase relative to
quit-chasing choices, but did not differ across participant groups. Exploratory
factor analysis identified a system of coordinated activity across prefrontal
executive-control networks that was greater in GD and CUD relative to HC
participants and was associated with increased chasing persistence across all
participants. CONCLUSIONS: Results provide evidence of shared and distinct
neurobiological mechanisms in substance and behavioral addictions, and lend
insight into potential cognitive interventions targeting loss-chasing behavior in
GD.
PMID- 28697387
TI - Influence of continental organic aerosols to the marine atmosphere over the East
China Sea: Insights from lipids, PAHs and phthalates.
AB - Total suspended particle (TSP) samples were collected during a marine cruise in
the East China Sea from May 18 to June 12, 2014. They were analyzed for solvent
extractable organic compounds (lipid compounds, PAHs and phthalates) using gas
chromatography/mass spectrometry (GC/MS) to better understand the sources and
source apportionment of aerosol pollution in the western North Pacific. Higher
concentrations were observed in the terrestrially influenced aerosol samples on
the basis of five-day backward air mass trajectories, especially for aerosols
collected near coastal areas. Phthalates were found to be the dominant species
among these measured compound classes (707+/-401ngm-3 for daytime and 313+/
155ngm-3 for nighttime), followed by fatty acids, fatty alcohols, n-alkanes and
PAHs. In general, the daytime abundances for these compounds are higher than
nighttime, possibly attributable to more intensive anthropogenic activities
during the daytime. The factor analysis indicates that biomass burning, fungal
activities and fossil fuel combustion maybe the main emission sources for organic
aerosols over the East China Sea. This study demonstrates that the East Asian
continent can be a natural emitter of biogenic and anthropogenic organics to the
marine atmosphere through long-range transport, which controls the chemical
composition and concentration of organic aerosols over the East China Sea.
PMID- 28697388
TI - Cord blood BPA level and child neurodevelopment and behavioral problems: The
Hokkaido Study on Environment and Children's Health.
PMID- 28697389
TI - Interaction patterns and toxicities of binary and ternary pesticide mixtures to
Daphnia magna estimated by an accelerated failure time model.
AB - Organisms in natural environments are often exposed to a broad variety of
chemicals, and the multi-chemical mixtures exposure may produce significant toxic
effects, even though the individual chemicals are present at concentrations below
their no-observed-effect concentrations. This study represents the first attempt
that uses the accelerated failure time (AFT) model to quantify the interaction
and toxicity of multi-chemical mixtures in environmental toxicology. We firstly
conducted the acute immobilization tests with Daphnia magna exposed to mixtures
of diazinon (DZN), fenitrothion (MEP); and thiobencarb (TB) in single, binary,
and ternary formulations, and then fitted the results to the AFT model. The 48-h
EC50 (concentration required to immobilize 50% of the daphnids at 48h) values for
each pesticide obtained from the AFT model are within a factor of 2 of the
corresponding values calculated from the single pesticide exposure tests,
indicating the methodology is able to provide credible toxicity values. The AFT
model revealed either significant synergistic (DZN and MEP; DZN and TB) or
antagonistic (MEP and TB) interactions in binary mixtures, while the interaction
pattern of ternary mixture depended on both the concentration levels and
concentration ratios of pesticides. With a factor of 2, the AFT model accurately
estimated the toxicities for 78% of binary mixture formulations that exhibited
significant synergistic effects, and the toxicities for all the ternary
formulations. Our results showed that the AFT model can provide a simple and
efficient way to quantify the interactions between pesticides and to assess the
toxicity of their mixtures. This ability may greatly facilitate the
ecotoxicological risk assessment of exposure to multi-chemical mixtures.
PMID- 28697390
TI - Exposure and risk characterization for dietary methylmercury from seafood
consumption in Kuwait.
AB - Seafood is an important source of essential nutrients; however, it can also
confer health risks from methylmercury (MeHg). In this paper, we evaluate the
levels of potential methylmercury exposure among Kuwaiti seafood consumers in
order to support the development of dietary recommendations for fish consumption
in Kuwait. Total mercury (HgT) concentration for most of the studied fish and
shellfish species were on average below the 0.5MUgg-1 Codex guideline. The
notable exception to this was Hamoor (Epinephelus coioides), which averaged
1.29MUgg-1 HgT and 0.55MUgg-1 MeHg. A dietary survey of 2393 households
demonstrated that large quantities of fish and shellfish are commonly consumed in
Kuwait (average consumption: 103gd-1). Most participants (53.6%) exceeded the
Tolerable Daily Intake of MeHg; this percent exceedance was as high as 78% in
children 6-12years of age. The majority (Mean: 50-51%) of Kuwaiti's dietary MeHg
exposure comes from the consumption of Hamoor; therefore, advisories to limit the
consumption of Hamoor may be necessary. Nutrient:Methylmercury ratios are
reported herein; these ratios may assist efforts to create dietary advice that
limits contaminant risk while promoting the nutritional benefits of seafood in
Kuwait.
PMID- 28697391
TI - Nutrients in one-carbon metabolism and urinary arsenic methylation in the
National Health and Nutrition Examination Survey (NHANES) 2003-2004.
AB - Exposure to inorganic arsenic (inAs), a potent toxicant, occurs primarily through
ingestion of food and water. The efficiency with which it is methylated to mono
and dimethyl arsenicals (MMA and DMA) affects toxicity. Folate, vitamins B12 and
B6 are required for 1C metabolism, and studies have found that higher levels of
these nutrients increase methylation capacity and are associated with protection
against adverse health effects from inAs, especially in undernourished
populations. Our aim was to determine whether 1C-related nutrients are associated
with greater inAs methylation capacity in a general population sample with
overall adequate nutrition and low levels of As exposure. Univariate and
multivariable regression models were used to evaluate the relationship of dietary
and blood nutrients to urinary As methylation in the National Health and
Nutrition Examination Survey (NHANES) 2003-2004. Outcome variables were the
percent of the sum of inAs and methylated As species (inAs+MMA+DMA) excreted as
inAs, MMA, and DMA, and the ratio of MMA:DMA. In univariate models, dietary
folate, vitamin B6 and protein intake were associated with lower urinary inAs%
and greater DMA% in adults (>=18years), with similar trends in children (6-18).
In adjusted models, vitamin B6 intake (p=0.011) and RBC folate (p=0.036) were
associated with lower inAs%, while dietary vitamin B12 was associated with higher
inAs% (p=0.002) and lower DMA% (p=0.030). Total plasma homocysteine was
associated with higher MMA% (p=0.004) and lower DMA% (p=0.003), but not with
inAs%; other blood nutrients showed no association with urinary As. Although
effect size is small, these findings suggest that 1C nutrients can influence inAs
methylation and potentially play an indirect role in reducing toxicity in a
general population sample.
PMID- 28697392
TI - Functional explanation and the problem of functional equivalence.
AB - The legitimacy of functional explanations in biology is threatened by a problem
first identified by Hempel: the problem of functional equivalence. In order for
the prevalence of a trait to be explained by its function, the function would
have to explain why that very trait is prevalent and not some other functionally
equivalent trait. But functions alone cannot meet this explanatory demand. I
argue that this is a problem not only for Nagelian deductive-nomological models
but also for etiological models of functional explanation. I contrast these
models with a dual model of adaptive explanation and design explanation. This
dual model largely circumvents the problem of functional equivalence, but divests
functions of much explanatory power.
PMID- 28697393
TI - Same medicine, different reasons: Comparing women's bodily experiences of
producing eggs for pregnancy or for profit.
AB - Women doing in vitro fertilization (IVF) to have a child describe it as painful
and emotionally draining. Egg donors undergo the same medical regimen for a
different reason - to produce eggs for another woman in exchange for thousands of
dollars - and describe it as quick and relatively painless. Medical researchers
typically compare bodily responses by variables such as gender, age, and health
status. We use the case of "egg production" to propose a new factor that may be
an important source of variation in bodily experience: an individual's reason for
undergoing the medical intervention in the first place. Using cluster analysis to
analyze an original survey of 50 IVF patients and 62 egg donors from the United
States, we find two distinct kinds of bodily experiences - "less intense" and
"more intense" - and the intensity of one's experience is associated with one's
reason for producing eggs: either to become pregnant or to donate them for money.
PMID- 28697394
TI - Dynamic thiol/disulphide homeostasis in patients with Uterine Myoma.
AB - BACKGROUND: The aim of this study is to measure and compare the dynamic thiol and
disulphide homeostasis between patients with Uterine Myoma (UM) and healthy
subjects. MATERIAL AND METHOD: A total of 54 patients with UM who were diagnosed
by transvaginal ultrasonography and 37 age- and body mass index-matched healthy
individuals were included in this study. Thiol/disulphide homeostasis was
measured by a novel automatic spectrophotometric method. RESULTS: The mean serum
native thiol, disulphide, and thiol levels were statistically lower in UM group
than those in the control group [(284.66+/-59.41MUmol/L vs. 320.98+/
56.17MUmol/L, P<0.0001), (17.27+/-5.59MUmol/L vs. 22.38+/-6.93MUmol/L, P<0.0001)
and (319.21+/-61.69 vs. 365.76+/-61.46MUmol/L, P<0.0001), respectively]. There
were no statistically significant differences in ratios of the disulphide/native
thiol, native thiol/total thiol, and disulphide/total thiol among patients with
UM versus healthy control group (P=0.096, 0.092, 0.092, respectively).
CONCLUSION: It was found that the native thiol, total thiol, and disulphide
levels in patients with UM decreased while the ratio of native thiol/disulphide
remained unchanged.It is necessary to investigate whether these findings have a
role in the etiology and clinical course of the UM.
PMID- 28697395
TI - Vaginal cervico-isthmic cerclage versus McDonald cerclage in women with a
previous failure of prophylactic cerclage: A retrospective study.
AB - AIM: Compare preterm births before 30 weeks of gestation in women with a previous
failed McDonald cerclage that benefit from another McDonald cerclage (or
simplified Shirodkar cerclage) or a vaginal cervico-isthmic cerclage. METHODS:
Women with a cerclage performed at the end of the first trimester of a singleton
pregnancy with a previous failed prophylactic McDonald cerclage were included in
this mutlicenric study involving four teaching hospitals. Comparisons between
groups were done using a chi square test and a student t-test. RESULTS: We
enrolled130 women, 85 in the vaginal cervico-isthmic cerclage group and 45 in the
classic cerclage group. There was no significant difference in the rate of
delivery after 30 weeks of gestation (92 versus 93% p=0.75). However in the
cervico isthmic cerclage, women were significantly older, presented more late
foetal loss and fewer live children in the cervico-isthmic cerclage group. Rate
of antenatal hospitalization andantenatal corticotherapy were significantly
higher in the classic cerclage group (69% versus 46%, p<0.05 and 56% versus 29%,
p<0.05). CONCLUSIONS: Rate of delivery before 30 weeks of gestation was not
significantly different between the two groups, but women in the vaginal cervico
isthmic cerclage group seem to be at higher risk for late foetal loss or
premature delivery. This procedure generates less threatened premature delivery,
thus, less hospitalization and antenatal corticotherapy. These arguments are
important for women with previous pregnancy loss.
PMID- 28697396
TI - Novel mutations in the exon 5, intron 2 and 3' UTR regions of IL-12B gene were
observed in clinically proven tuberculosis patients of south India.
AB - Interleukin-12 (IL-12) is formed by the interaction of IL-12p35 and IL-12p40
expressed independently from IL-12A and IL-12B genes. This interleukin plays
prominent role in the T-helper type-1 (Th1) response against intracellular
pathogens. Variations in IL-12B gene causes disruption of various activities one
of them is suppression of Th1 response and is one of the characteristic features
observed in patients with active tuberculosis. Hence, in the present study IL-12B
gene status was evaluated in 50 new sputum smear-positive pulmonary tuberculosis
patients (NSP-PTB) as identified by Ziehl-Nielsen (ZN) staining and 50 apparently
healthy control subjects (HCS) who were sputum smear-negative. The sequence
analysis showed novel missense mutations p.Ser205Ile, p.Leu206Glu, p.Pro207Ser,
p.Glu209Lys, p.Val210Ser, p.(Ser205_Cys327delinsIleGlu) and
p.(Lys217_Leu218delinsIle) were found in exon 5 of the IL-12B gene in nine
patients resulting formation of inactive IL-12 and three patients showed novel
frame shift mutations p.(Asn222Leufs*23) in exon 5 of causing the formation of
truncated protein. Several mutations were noted in intron 2 of the IL-12B gene in
5 patients and in 13 patients mutations were observed in 3' UTR region. All
together 30/50 patients (60%) showed mutations in IL-12B gene. Decreased levels
of interferon-gamma (IFN-gamma) and IL-12 as determined by ELISA and flow
cytometry were observed in the peripheral blood mononuclear cell culture
supernatants in TB patients having mutations compared with control subjects.
Further, in silico analysis revealed due to frame shift mutations in exon 5 at
Asn222 resulted in deletion of functional fibronectin type-III (FN3) domain which
leads to formation of inactive IL-12 in these patients.
PMID- 28697397
TI - Reproducibility of characteristic marks on fired cartridge cases from five
Chinese Norinco QSZ-92 9*19mm pistols.
AB - Reproducibility of characteristic marks on fired cartridge cases from five
Chinese Norinco QSZ-92 9*19mm pistols over the course of 3070 shots is addressed
using an Evofinder(r) system. The first 20 cartridges are all studied, while one
random sample out of every ten consecutively fired cartridge cases is studied for
the rest 3050 rounds. As such, a total of 325 cartridges are entered into the
system for each pistol and a database consisting of 1625 cartridges from five
pistols is established in this paper. Both onscreen examination and automatic
correlation are used to examine the reproducibility. In the onscreen examination
process, it is possible for firearm examiners to positively identify the first
cartridge to the 500th, 1000th, 1500th, 2000th, 2500th, 3000th, 3070th cartridge.
In the automatic correlation process, the first cartridge of each firearm is
separately performed correlation against the database. It is found that the
similarity score for match objects changes slightly as the shot number increases,
indicating slight variations of marks. However, these variations have not
prohibited the Evofinder(r) system to make correct correlation and rank 100% of
the known match objects on the top of the correlation list by either firing pin
impression or breech face mark. Thus, the reproducibility is proved statistically
and objectively in this paper.
PMID- 28697398
TI - PUFAs and PUAs production in three benthic diatoms from the northern Adriatic
Sea.
AB - The production of polyunsaturated aldehydes (PUAs) has been reported by many
planktonic diatoms, where they have been implicated in deleterious effects on
copepod reproduction and growth of closeby microbes or suggested as infochemicals
in shaping plankton interactions. This study investigates the production of PUAs
by diatoms commonly occurring in the microphytobenthic communities in temperate
regions: Tabularia affinis, Proschkinia complanatoides and Navicula sp. Results
highlight the production of PUAs by the three benthic diatoms during stationary
and decline phases, with intracellular concentrations from 1.8 to 154.4 fmol cell
1, which are within the range observed for planktonic species. The existence of a
large family of PUAs, including some with four unsaturations, such as
decatetraenal, undecatetraenal and tridecatetraenal, was observed. Since
particulate and dissolved PUAs were positively correlated, together with cell
lysis, equivalent concentrations may be released during late growth stages, which
may affect benthic invertebrates grazing on them and other microalgae.
PMID- 28697399
TI - Patellar bracing affects sEMG activity of leg and thigh muscles during stance
phase in patellofemoral pain syndrome.
AB - BACKGROUND: Decreases in patellofemoral pain symptoms with bracing treatment have
been established; but, the mechanisms remain unclear. The purpose of this study
was to determine the immediate and long-term effects of the patellar bracing on
electromyography (EMG) activity of the Vastus Medialis (VM) and Lateralis (VL),
Rectus Femoris, lateral Gastrocnemius, Biceps Femoris and Semitendinosus (ST)
muscles during level walking. METHODS: 12 eligible women aged 20-30 years with
diagnosis of patellofemoral pain participated in the before and after study.
Intervention consisted of 8 weeks of patellar bracing. First, patients were
tested without brace, then with a brace, and finally eight weeks later without a
brace. Surface EMG activation of the selected muscles during level walking was
recorded. RESULTS: After eight weeks of patellar bracing, EMG activity of VM
muscle was significantly higher when compared to first session without brace
(p=0.011) at mid-stance sub-phase. Additionally, EMG activity of ST muscle during
first session with brace was significantly lower when compared to first session
without brace at mid-stance sub-phase (without brace) (p=0.012). EMG activity of
VM muscle after eight weeks of patellar bracing was significantly higher than the
first session without brace at late stance and preswing sub-phase (p=0.013).
CONCLUSION: Long-term wearing of patellar bracing increases EMG activity of VM
during mid-stance and late stance and preswing sub-phases of gait and immediate
effect of patellar brace is decrease of EMG activity of ST muscle during mid
stance.
PMID- 28697400
TI - An adaptive finite element simulation of fretting wear damage at the head-neck
taper junction of total hip replacement: The role of taper angle mismatch.
AB - An adaptive finite element simulation was developed to predict fretting wear in a
head-neck taper junction of hip joint implant through a two dimensional (2D)
model and based on the Archard wear equation. This model represents the most
critical section of the head-neck junction which was identified from a 3D model
of the junction subjected to one cycle of level gait loading. The 2D model was
then used to investigate the effect of angular mismatch between the head and neck
components on the material loss and fretting wear process over 4 million gait
cycles of walking. Generally, junctions with distal angular mismatches showed a
better resistance to fretting wear. The largest area loss in the neck after 4
million cycles of loading was 1.86E-02mm2 which was found in the junction with a
proximal mismatch angle of 0.124 degrees . While, the minimum lost area (4.30E
03mm2) was found in the junction with a distal angular mismatch of 0.024 degrees
. Contact stress, amplitude of sliding and contact length were found as the key
parameters that can influence the amount of material loss and the process of
fretting wear damage. These parameters vary over the fretting wear cycles and are
highly dependent on the type and magnitude of the taper angle mismatch. This
study also showed that lost area does not have a linear relationship with the
mismatch angle of taper junctions.
PMID- 28697401
TI - Fatigue failure of plated osteoporotic proximal humerus fractures is predicted by
the strain around the proximal screws.
AB - The high rate of required reoperation indicates that treatment of fragility
fractures at the proximal humerus still remains a major challenge in trauma
surgery. Improved fixation approaches are needed. Several limitations of the
conventional implant development process involving experimental testing could be
overcome by using computer models that would allow systematic and efficient
analyses. However, such models require experimental validation. This study
investigated if linear elastic continuum finite element (FE) models can predict
experimental fatigue failure in locking plate fixation of osteoporotic proximal
humerus fractures. Three-part fractures were created in twenty fresh-frozen
proximal humeri of elderly donors, stabilized with angular stable plate
osteosythesis and tested to failure in a previously developed experimental setup
using a cyclic loading protocol with increasing peak load. Case-specific, linear
elastic FE models of the instrumented samples were created from CT images and
loaded virtually by mimicking the experimental conditions. Average principal
strains were evaluated in cylindrical regions around the proximal screws.
Parametric sensitivity analysis was performed to investigate the effects of
specific model parameters on the results. The number of cycles to failure was
10500 +/- 3300 (mean +/- SD, range: 3100 - 16400) and showed a strong logarithmic
correlation with the average compressive principal strain around the screws (R2 =
0.90). These results suggest that the latter parameter may be used as a surrogate
estimate for construct stability under cyclic loading. The computationally cheap
linear elastic continuum FE analysis could be used as an efficient screening tool
for optimization and development of implants. Further work is required to
investigate if the findings of this study apply to other loading modes and bone
implant constructs.
PMID- 28697402
TI - Functional biocompatibility testing of silicone breast implants and a novel
classification system based on surface roughness.
AB - PURPOSE: Increasing numbers of women undergo breast implantation for cosmetic and
reconstructive purposes. Contracture of the fibrous capsule, which encases the
implant leads to significant pain and reoperation. Texture, wettability and the
cellular reaction to implant surfaces are poorly understood determinants of
implant biocompatibility. The aim of this study was to evaluate the in-vitro
characteristics of a range of commercial available implants using a macrophage
based assay of implant biocompatibility and a quantitative assessment of
wettability and texture. METHODS: Thirteen commercially available surfaces were
subjected to wettability and texture characterisation using scanning and laser
confocal microscopy. THP-1 macrophages were cultured on their surfaces and
assessed using Integrin alphaV immunocytochemistry, SEM and RT-PCR for the
expression of TNF-Alpha, IL-6, IL-10 and a cytokine array for the production of
TNF-alpha, IL-10, IL-1RA and IL1beta; important indicators of inflammation and
macrophage polarization. RESULTS: Textured surfaces can be accurately sub
categorized dependent upon roughness and re-entrant features into four main types
(macro, micro, meso and nano-textured surfaces). Significant (P < 0.0001)
differences in implant hydrophobicity and texture exist. Certain surfaces
promoted poor macrophage polarization and an innate potential to foster a
proinflammatory response. A subgroup analysis showed that texture had a variable
effect on markers of inflammation in these surfaces. CONCLUSIONS: We propose a
classification of implant surfaces based on roughness and present a macrophage
based assay of breast implant biocompatibility with a quantitative assessment of
implant wettability and texture. The breast implant surface-cell interaction is
variable and sufficient to alter healing response and capsular contracture fate
in-vivo.
PMID- 28697403
TI - Ameliorative efficacy of bioencapsulated Chironomous larvae with Shilajit on
Zebrafish (Danio rerio) exposed to Ionizing radiation.
AB - Using Zebrafish (Danio rerio) as a model organism, we evaluated the
radioprotective and antioxidant effects of the Indian traditional medicine
Shilajit exposed to X-Ray. The Zebrafish were divided into three experimental
groups and control group, each group containing ten fish. The three experimental
fish groups, group I, group II and group III were fed with 3, 5 and 7ppm shilajit
encapsulated Chironomous larvae and group IV served as a control fed with non-
encapsulated larvae. After 60 days of feeding trial, fish were irradiated with X
Ray at a single acute dose of 1Gy. 72h of post-irradiation, each experimental
fish were observed for its morphological, behavioral, clinical symptoms,
antioxidant levels and DNA damage were evaluated. Among the experimental groups
5ppm shilajit encapsulated Chironomous larvae fed fish group shows the most
significant radioprotective effects compared with control and other experimental
fish groups. The present study indicates that shilajit have significant
radioprotective and antioxidant enhancing capability. The humus substance of
shilajit may be the factor responsible to react with radiation-derived or
radiation related reactive species on zebrafish.
PMID- 28697404
TI - IL-33 improves wound healing through enhanced M2 macrophage polarization in
diabetic mice.
AB - IL-33 is a newly discovered member of the IL-1 family and has been identified as
a potent inducer of Th2 type immunity. Emerging evidence imply that IL-33 may
also act as an alarm to alert the immune system when released by epithelial
barrier tissues during trauma or infection. In this study, we further investigate
the potential efficacy of IL-33 on dermal wound healing in streptozotocin-induced
diabetic mice. A full-thickness skin wound was generated on the back of diabetic
mice and treated with IL-33 or vehicle topically. Our data showed that IL-33
delivery contributed to diabetic wound closure with wounds gaping narrower and
exhibiting elevated re-epithelialization. IL-33 promoted the new extracellular
matrix (ECM) deposition and angiogenesis formation, which indicates an important
role of IL-33 on matrix synthesis and neovascularization. Meanwhile, IL-33
accelerated the development of M2 macrophages in wound sites in vivo, and
amplified IL-13-induced polarization of bone marrow-derived macrophages toward a
M2 phenotype in vitro. Furthermore, IL-33-amplified M2 macrophages augmented the
proliferation of fibroblasts and ECM deposition. All together, these results
strongly suggest manipulation of IL-33-mediated signal might be a potential
therapeutic approach for diabetic skin wounds.
PMID- 28697405
TI - Neurodevelopmental outcome of Italian preterm children at 1year of corrected age
by Bayley-III scales: An assessment using local norms.
AB - BACKGROUND: Premature birth is often associated with neurodevelopmental
difficulties throughout childhood. In the first three years of life, the Bayley
Scales of Infant and Toddler Development-Third Edition (Bayley-III) constitute
one of the most used tools for assessing child development. Since Bayley-III
original norms are based on United States (US) population, it remains uncertain
whether their use in other countries (e.g., European) is appropriate. AIMS: This
research aimed to examine neurodevelopment of preterm infants and full-term
infants, using Bayley-III US norms in comparison to Italian (IT) norms. Patterns
of developmental outcomes for both infant groups were also explored. METHODS: 104
preterm and 58 full-term infants were included in the study. Bayley-III was used
for neurodevelopmental assessment at 1year of corrected age, considering both IT
and US norms for scores computation. RESULTS: Comparing scores obtained with IT
vs US norms, differences in means were all significant across five subscales
(p<0.05 at least) for preterm infants, whereas for full-term peers significant
differences were found only for Receptive Language and Fine Motor subscales
(p<0.001). Effect size (eta2) ranged from 0.22 to 0.94. Within each group,
significant discrepancies across subscales were found. Moreover, Italian preterm
infants had significantly lower performances than full-term peers, excepting for
Expressive Language and Gross Motor subscales. CONCLUSIONS: As regards to Italian
1-year children, our study seems to provide evidence for the tendency of Bayley
III US norms to overestimate development compared to IT norms. These findings
emphasize the need to early detect children at risk for developmental delay and
to plan early intervention.
PMID- 28697407
TI - Digit ratio (2D:4D) and muscular strength in adolescent boys.
AB - Using a cross-sectional design, this study quantified the relationship between
the digit ratio (2D:4D) and muscular strength in 57 adolescent boys. 2D:4D was
very likely a moderate negative correlate of handgrip strength, even after
adjustment for age and body size. This result may reflect the organizational
benefits of prenatal testosterone.
PMID- 28697406
TI - Efficacy of pharmacologic closure of patent ductus arteriosus in small-for
gestational-age extremely preterm infants.
AB - BACKGROUND: Optimal management of the patent ductus arteriosus (PDA) in preterm
infants remains controversial. Therefore, studies identifying infants who are
most likely to benefit from PDA treatment are needed. AIM: We sought to examine
if significant intrauterine growth restriction, defined by birth weight z-score,
reduces the efficacy of PDA closure with indomethacin or ibuprofen and thereby
increases the need for surgical closure of PDA after pharmacologic treatment.
STUDY DESIGN, SUBJECTS, AND OUTCOME MEASURES: We studied infants 23-28weeks'
gestation born 2006-2013 at NICHD Neonatal Research Network centers. We examined
the responses to PDA treatment with indomethacin and/or ibuprofen and whether the
PDA was subsequently closed surgically. Logistic regression generated adjusted
odds ratios (ORs) for the associations between the z-score groups (<-2, -2 to
0.5, and >-0.5) and PDA surgery following pharmacologic treatment. RESULTS: 5606
infants were diagnosed with PDA; 3587 (64.0%) received indomethacin or ibuprofen
or both, and 909 (25.3%) underwent PDA surgery. Mothers of infants with PDA non
closure were less likely to have hypertension (19% vs. 28%). Infants with non
closure were more likely to be female (53% vs. 49%), have lower gestational age
and birth weight and to develop sepsis (42% vs. 31%). Compared to infants with z
score>-0.5, PDA surgery was increased among infants with z-score -2 to -0.5
(OR=1.23; 95% CI 1.02-1.47) but not among infants with z-score<-2. CONCLUSION:
Infants with birth weight z-score -2 to -0.5 are more likely than normally grown
infants to require PDA surgery following pharmacologic treatment.
PMID- 28697408
TI - A finding in genetic polymorphism analysis study: A case of non-mosaic 47, XXX
without manifestations.
AB - Trisomy X (47, XXX) is a sex chromosome aneuploidy condition in which females
have an extra X chromosome, compared to the 46, XX karyotype in typical females.
There is considerable variation in the phenotype, with some individuals very
mildly affected and others with more significant physical and psychological
features. However, the trisomy X in this case, without any of these phenotype, is
rarely reported. Here, we report a case found during DNA sample collection in a
study of genetic polymorphism analysis of loci in Chinese ethnic group, of a
female with neither laboratory or clinical signs of Triple X syndrome. She was
born at her mother's 60years old and her father's 62years old. Advanced maternal
age was found acting as a significant risk factor of Triplo-X. Moreover, her
child are also born without manifestations of 47, XXX syndrome. Pedigree study
demonstrated the normal karyotype of the children. A diagnosis of 47XXX was made
on the basis of a chromosomal study. Therefore, laboratory investigations
(including PCR amplification, more than two kinds of X-STR genotyping, G-banding
karyotyping analysis and Pedigree study) are applied to rule out the possibility
of Mosaicism (45, X0/47, XXX) and ascertain her 47XXX karyotype without mosaic.
The objective of this study was to report a case of trisomy X, diagnostic
investigation and management of the case, and to analysis the genetically
possible reasons behind the case. To our knowledge, this case is a rare one,
found in DNA sample collection for the estimation of gene frequency in the
process of genetic polymorphism study, of non-mosaic 47, XXX without signs of
physical syndrome and born healthy children. In this study, it revealed that the
proportion of trisomy X would be more than official statistics and risk of
systemic disabilities is lower than estimated. Moreover, we found out that sample
mixture and mosaicism act as the interference factors in forensic test.
Therefore, we draw the conclusion that attentions and certain improved methods
should be applied to the diagnosis of non-mosaic triple X, which is of great
significance in decreasing the interruptions in the whole process of forensic and
paternity identification.
PMID- 28697409
TI - Influence of the RPL34 gene on the growth and metastasis of oral squamous cell
carcinoma cells.
AB - BACKGROUND: Oral squamous cell carcinoma (OSCC) accounts for almost 3% of all
malignant tumors all over the world. This study aims to investigate the
correlation of RPL34 with the cell growth and metastasis of oral squamous cell
carcinoma (OSCC) as well as its clinical prognosis. METHOD: Quantitative real
time polymerase chain reaction (qRT-PCR) and immunohistochemistry were conducted
to determine the RPL34 expression in 85 OSCC tissues and 30 normal oral mucosa
tissues. Besides, OSCC cell lines SCC-4 were divided into blank group, negative
control (NC) group and RPL34-shRNA group. The qRT-PCR and western blot were
performed to measure RPL34 expression, CCK-8 and flow cytometry to observe cell
growth and apoptosis, and wound healing and transwell to detect cell migration
and invasion. RESULTS: The RPL34 gene expression was up-regulated in OSCC tissues
and cells. The RPL34 expression was significantly correlated with differentiation
degree, TNM stage and lymph node metastasis. Patients with positive RPL34
expression had a poorer prognosis. After inhibition of RPL34 expression, the
proliferation of SCC-4 cells was slowed down at 24h, 48h, 72h and 96h
respectively, and both the migration distance and the number of invasive cells
were reduced, while there was an increase in the ratio of cells at G0/G1 stage
and cell apoptosis. CONCLUSION: The RPL34 gene was highly expressed in OSCC,
while silencing RPL34 could block cell proliferation and metastasis, but promote
cell apoptosis, suggesting the RPL34 gene to be a new promising clinical target
for OSCC therapy.
PMID- 28697410
TI - The effect of interpersonal rejection on attentional biases regarding thin-ideal
and non-thin images: The moderating role of body weight- and shape-based self
worth.
AB - Interpersonal dysfunction and weight/shape-based self-worth have been implicated
as key constructs for eating disorders, although the relationship between these
two concepts is under-researched. This study investigated the moderating role of
weight/shape-based self-worth in terms of the impact of interpersonal rejection
on attentional bias regarding thin-ideal and non-thin images. Participants were
94 females without an eating disorder, who were exposed to either interpersonal
rejection or acceptance (using the Cyberball paradigm), and subsequently assessed
in terms of their attentional biases regarding thin-ideal and non-thin images.
Results revealed that weight/shape-based self-worth moderated the relationship
between interpersonal rejection/acceptance and attentional biases for thin-ideal
(but not non-thin) images. Specifically, participants with a greater tendency to
base their self-worth on weight/shape demonstrated reduced avoidance of thin
ideal images when rejected relative to those who were accepted. The findings
support the role of interpersonal rejection in eliciting attentional disturbances
among those with higher body weight/shape-based self-worth.
PMID- 28697411
TI - Electron velocity map imaging and theoretical study on CuXH (X=O and S) anions.
AB - Vibrationally resolved photoelectron spectra of CuOH- and CuSH- have been
determined via velocity map imaging method to investigate the transitions of
X1A'<-X2A' at 532nm. Adiabatic detachment energies of CuOH- and CuSH- are
assigned to 0.995(12) and 1.098(12) eV, respectively. Combined theoretical
calculations with Franck-Condon simulations, it allows extracting the vibrational
frequencies in neutral, which yields 629(32) cm-1 with CuO stretching mode and
387(24) cm-1 with CuS stretching mode for CuXH (X=O and S). Parallel transition
properties of photoelectron angular distributions (PADs) for both species are
correlated to the photodetachment of SOMO orbitals, which mainly involved in the
Cu atom s orbital and partial s orbital in other atoms. Based on chemical bonding
analyses (Wiberg, NAO, Mayer, NRT, and ELF), it is suggested that a trend is
observed with a subtle variation of covalent component from weak covalent
behavior between CuO in CuOH-1/0 to stronger covalent bonding between CuS in CuSH
1/0 (especially for non-ignorable covalent component in CuSH species) though
ionic bonding dominates both in CuO and CuS bonds for the two systems.
PMID- 28697412
TI - Conformation and activity alteration of horseradish peroxidase induced by the
interaction with gene carrier polyethyleneimines.
AB - Polyethyleneimine (PEI) has long been considered as "golden standard" for
polymeric gene delivery carriers. However the molecular basis of the cytotoxicity
of PEI is poorly understood. Little is known about the effects of PEI on the
structure and functions of biomacromolecules. In this work, fluorescence, UV-vis
absorption, circular dichroism spectroscopy were conducted to investigate the
influence of PEI of average molecular weight 25, 10 and 1.8kDa (denoted as
PEI25k, PEI10k and PEI1.8k) on the conformation of horseradish peroxidase (HRP)
and its catalytic efficiency. Zeta-potential measurement and isothermal titration
calorimetry were used to reveal the mechanism of the interaction between PEIs and
HRP. PEIs were found to bind onto the surface of HRP predominantly via
hydrophobic interaction and hydrogen bond or van der Waals interaction. The
complex formation between HRP and PEI induced a more compact conformation of the
enzyme and an increased hydrophobicity of the microenvironment surrounding heme
pocket. The conformational change of HRP had little impact on the affinity
towards H2O2 and phenol. However, the increase in the non-planarity of porphyrin
ring in the heme group led to an increase in the exposure degree of the active
center and thus an enhancement of catalytic efficiency of HRP in the presence of
high molecular weight PEIs (PEI25k and PEI10k). The polymer size played an
important role in PEI-HRP interaction. PEI of low molecular weight (PEI1.8k) was
less efficient to alter the conformation and catalytic activity of HRP in aqueous
solutions.
PMID- 28697413
TI - Using size exclusion chromatography to monitor the synthesis of melanins from
catecholamines.
AB - We have employed size exclusion chromatography (SEC) to the study of the auto-
and Cu2+-mediated oxidation of the catecholamines, dopamine, epinephrine and
norepinephrine, into melanins. We observed that, due to non-size exclusion
mediated effects, the catecholamines and some of the low molecular mass
intermediates generated during the oxidation reactions, could be resolved from
each other and from the high molecular mass pigment generated. Thus, SEC allowed
us to monitor the disappearance of the catecholamine starting compounds, the
appearance and subsequent disappearance of the low molecular mass chromophores
generated in the initial phase of the reactions and the appearance of the high
molecular mass melanins. In the process of this research, we observed that many,
mostly anionic polysaccharides (PS), enhanced both the auto- and Cu2+-mediated
oxidation of all three catecholamines. SEC analyses of reaction mixtures
involving PS suggested that very high molecular mass aggregates between PS and
melanins can be generated. In addition, SEC analysis allowed us to verify the
efficiency of the dialysis purification process employed to obtain pure and dried
melanin materials for cell-biological studies.
PMID- 28697414
TI - Analytical methodologies for broad metabolite coverage of exhaled breath
condensate.
AB - Breath analysis has been gaining popularity as a non-invasive technique that is
amenable to a broad range of medical uses. One of the persistent problems
hampering the wide application of the breath analysis method is measurement
variability of metabolite abundances stemming from differences in both sampling
and analysis methodologies used in various studies. Mass spectrometry has been a
method of choice for comprehensive metabolomic analysis. For the first time in
the present study, we juxtapose the most commonly employed mass spectrometry
based analysis methodologies and directly compare the resultant coverages of
detected compounds in exhaled breath condensate in order to guide methodology
choices for exhaled breath condensate analysis studies. Four methods were
explored to broaden the range of measured compounds across both the volatile and
non-volatile domain. Liquid phase sampling with polyacrylate Solid-Phase
MicroExtraction fiber, liquid phase extraction with a polydimethylsiloxane patch,
and headspace sampling using Carboxen/Polydimethylsiloxane Solid-Phase
MicroExtraction (SPME) followed by gas chromatography mass spectrometry were
tested for the analysis of volatile fraction. Hydrophilic interaction liquid
chromatography and reversed-phase chromatography high performance liquid
chromatography mass spectrometry were used for analysis of non-volatile fraction.
We found that liquid phase breath condensate extraction was notably superior
compared to headspace extraction and differences in employed sorbents manifested
altered metabolite coverages. The most pronounced effect was substantially
enhanced metabolite capture for larger, higher-boiling compounds using
polyacrylate SPME liquid phase sampling. The analysis of the non-volatile
fraction of breath condensate by hydrophilic and reverse phase high performance
liquid chromatography mass spectrometry indicated orthogonal metabolite coverage
by these chromatography modes. We found that the metabolite coverage could be
enhanced significantly with the use of organic solvent as a device rinse after
breath sampling to collect the non-aqueous fraction as opposed to neat breath
condensate sample. Here, we show the detected ranges of compounds in each case
and provide a practical guide for methodology selection for optimal detection of
specific compounds.
PMID- 28697415
TI - A high area, porous and resistant platinized stainless steel fiber coated by
nanostructured polypyrrole for direct HS-SPME of nicotine in biological samples
prior to GC-FID quantification.
AB - The surface of a stainless steel fiber was made porous, resistant and cohesive
using electrophoretic deposition and coated by the nanostructured polypyrrole
using an amended in-situ electropolymerization method. The coated fiber was
applied for direct extraction of nicotine in biological samples through a
headspace solid-phase microextraction (HS-SPME) method followed by GC-FID
determination. The effects of the important experimental variables on the
efficiency of the developed HS-SPME-GC-FID method, including pH of sample
solution, extraction temperature and time, stirring rate, and ionic strength were
evaluated and optimized. Under the optimal experimental conditions, the
calibration curve was linear over the range of 0.1-20MUgmL-1 and the detection
limit was obtained 20ngmL-1. Relative standard deviation (RSD, n=6) was
calculated 7.6%. The results demonstrated the superiority of the proposed fiber
compared with the most used commercial types. The proposed HS-SPME-GC-FID method
was successfully used for the analysis of nicotine in urine and human plasma
samples.
PMID- 28697416
TI - Depression and anxiety symptoms are associated with white blood cell count and
red cell distribution width: A sex-stratified analysis in a population-based
study.
AB - BACKGROUND: Depression and anxiety are two common mood disorders that are both
linked to systemic inflammation. Increased white blood cell (WBC) count and red
cell distribution width (RDW) are associated with negative clinical outcomes in a
wide variety of pathological conditions. WBC is a non-specific inflammatory
marker and RDW is also strongly related to other inflammatory markers. Therefore,
we proposed that there might be an association between these hematological
inflammatory markers and depression/anxiety symptoms. OBJECTIVE: The primary
objective of this study was to examine the association between depression/anxiety
symptoms and hematological inflammatory markers including WBC and RDW in a large
population-based study. METHODS: Symptoms of depression and anxiety and a
complete blood count (CBC) were measured in 9274 participants (40% males and 60%
females) aged 35-65 years, enrolled in a population-based cohort (MASHAD) study
in north-eastern Iran. Symptoms of depression and anxiety were evaluated using
the Beck Depression and Anxiety Inventories. RESULTS: The mean WBC count
increased with increasing severity of symptoms of depression and anxiety among
men. Male participants with severe depression had significantly higher values of
RDW (p<0.001); however, this relationship was less marked among women (p=0.004).
In addition, men (but not women) with severe anxiety symptoms had significantly
higher values of RDW (p<0.001). Moreover, there was a negative association
between red blood cell (RBC) and mean corpuscular hemoglobin (MCH) and symptoms
of depression/anxiety. CONCLUSION: Our results suggest that higher depression and
anxiety scores are associated with an enhanced inflammatory state, as assessed by
higher hematological inflammatory markers including WBC and RDW, even after
adjusting for potential confounders.
PMID- 28697417
TI - Tumor characteristics and family history in relation to mammographic density and
breast cancer: The French E3N cohort.
AB - BACKGROUND: Mammographic density is a known heritable risk factor for breast
cancer, but reports how tumor characteristics and family history may modify this
association are inconsistent. METHODS: Dense and total breast areas were assessed
using CumulusTM from pre-diagnostic mammograms for 820 invasive breast cancer
cases and 820 matched controls nested within the French E3N cohort study. To
allow comparisons across models, percent mammographic density (PMD) was
standardized to the distribution of the controls. Odds ratios (OR) and 95%
confidence intervals (CI) of breast cancer risk for mammographic density were
estimated by conditional logistic regression while adjusting for age and body
mass index. Heterogeneity according to tumor characteristic and family history
was assessed using stratified analyses. RESULTS: Overall, the OR per 1 SD for PMD
was 1.50 (95% CI, 1.33-1.69). No evidence for significant heterogeneity by tumor
size, lymph node status, grade, and hormone receptor status (estrogen,
progesterone, and HER2) was detected. However, the association of PMD was
stronger for women reporting a family history of breast cancer (OR1SD=2.25; 95%
CI, 1.67-3.04) than in women reporting none (OR1SD=1.41; 95% CI, 1.24-1.60;
pheterogeneity=0.002). Similarly, effect modification by FHBC was observed using
categories of PMD (pheterogeneity=0.02) with respective ORs of 15.16 (95% CI,
4.23-54.28) vs. 3.14 (95% CI, 1.89-5.22) for >=50% vs. <10% PMD. CONCLUSIONS: The
stronger association between mammographic density and breast cancer risk with a
family history supports the hypothesis of shared genetic factors responsible for
familial aggregation of breast cancer and the heritable component of mammographic
density.
PMID- 28697418
TI - Suicidal ideation and attentional biases in children: An eye-tracking study.
AB - BACKGROUND: Despite theoretical and empirical evidence for a heighted
responsiveness to signals of social-threat in suicidal individuals, no studies to
date have examined whether this responsiveness might also manifest in the form of
specific biases in attention to interpersonal stimuli. The current study,
therefore, examined the presence and nature of attentional biases for facial
expressions of emotion in children with and without a history of suicidal
ideation (SI). METHOD: Participants were 88 children (44 with a history of SI and
44 demographically and clinically matched controls without such history)
recruited from the community. The average age of children was 9.26 years (44.3%
female; 67.0% Caucasian). Children's history of SI was assessed via structured
interviews with children and their parent. Attentional biases were assessed using
a dot probe task and included fearful, happy, and sad facial stimuli and focused
on eye tracking and reaction time indices of attentional bias. RESULTS: Children
with a history of SI exhibited significantly greater gaze duration toward fearful
faces. The findings appeared to be at least partially independent of children's
history of major depression or anxiety disorders or their current depressive or
anxious symptoms. LIMITATIONS: The study is limited by its cross-sectional
design, which precludes any causal conclusions regarding the role of attentional
biases in future suicide risk. CONCLUSIONS: Our results suggest that children
with a history of SI exhibit biases in sustained attention toward socially
threatening facial expressions. Pending replications, these findings might
represent a new avenue of suicide risk assessment and intervention.
PMID- 28697419
TI - Prior depression and incident back pain among military registered nurses: A
retrospective cohort study.
AB - BACKGROUND: Occupational back pain rates are substantial among registered nurses,
and nurses also report high rates of depression. The role of depression as a
potential predictor of back pain among nurses appears understudied. OBJECTIVES:
The objective of the study was to determine whether a history of depression
predicted incident back pain in a population of military registered nurses when
controlling for relevant risk factors. DESIGN: We employed a retrospective cohort
approach using longitudinal data in which gender-specific subject groups were
followed from the beginning of duty as a registered nurse to the occurrence of an
outcome, or to censoring due to completion of service or the end of available
data. PARTICIPANTS: This study included all United States Army registered nurses
who began work during 2011-2014 without evidence of prior back pain in clinical
records. METHODS: Data from automatically-collected medical and administrative
sources were combined and used to provide 2134 person-years of observation on
1248 individuals. These data were organized at the person-month level in a panel
data structure to support discrete-time multivariable logistic regression models.
The models examined the relationships between prior depression, Body Mass Index,
the presence of prior combat duty and selected control variables and the outcome,
the incident occurrence of back pain. RESULTS: The incidence rate of back pain
was 18.6 per 100 person-years and the period prevalence was 31.7%. Prior
depression was a statistically-significant predictor of incident back pain among
female subjects (odds ratio [OR]: 1.75, 95% confidence interval [CI]: 1.08-2.83,
P-value<0.05). Body Mass Index of 30kg/m2 or greater, prior combat deployments,
and age 36 years or older was each associated with back pain for male and female
nurses. CONCLUSIONS: The study's findings provide the first evidence of a
temporal link between antecedent depression and later back pain among female
military nurses. High Body Mass Index was found to be a further, modifiable risk
factor for back pain in this population.
PMID- 28697420
TI - Familial early infantile epileptic encephalopathy and cardiac conduction
disorder: A rare cause of SUDEP in infancy.
PMID- 28697421
TI - Meat quality attributes of Agile Wallabies.
AB - Meat quality traits of Agile Wallaby (Macropus agilis) M. longissimus (loin) and
M. semimembranosus (topside) were investigated. Both muscles exhibited a
relatively high pH (>5.7) and dark colour (L*-, a*-, and b*-values). Aging the
loins from 2 to 21days p.m. had a significant effect on shear force. However, the
results regarding shear force, myofibrillar fragmentation index (MFI) and
degradation of desmin and troponin-T suggested that the aging response largely
occurred within 2days p.m. Suspension of carcasses from one leg resulted in a
side effect on shear force of the loin at 2 and 7days p.m., but not on sarcomere
length or MFI. Topsides from the free hanging leg exhibited lower shear force
values (33 vs 42N) and greater sarcomere lengths (2.51 vs 1.84MUM). Tenderness,
juiciness, flavour and overall liking were higher for loins than topsides.
Sensory scores for the loin and topside were slightly lower and similar,
respectively, to those reported for lamb.
PMID- 28697422
TI - The relationship between trauma centrality, self-efficacy, posttraumatic stress
and psychiatric co-morbidity among Syrian refugees: Is gender a moderator?
AB - This study examined the inter-relationship between trauma centrality, self
efficacy, posttraumatic stress disorder (PTSD) and psychiatric co-morbidity among
a group of Syrian refugees living in Turkey, and whether gender would moderate
the mediational effect of self-efficacy on the impact of trauma centrality on
distress. Seven hundred and ninety-two Syrian refugees completed the Harvard
Trauma Questionnaire, General Health Questionnaire-28, Centrality of Event Scale
and Generalized Self-Efficacy Scale. The results showed that 52% met the cutoff
for PTSD. Trauma centrality was positively correlated with PTSD, psychiatric co
morbidity and self-efficacy. Self-efficacy was negatively correlated with PTSD
only. Gender did not moderate the mediational effect of self-efficacy on the path
between trauma centrality and distress outcomes. To conclude, following exposure
to traumatic events, more than half reported PTSD. Perception of the future and
identity construction was affected. Signs of psychological distress were evident,
alongside resilience, regardless of gender.
PMID- 28697423
TI - Early improvement as a resilience signal predicting later remission to
antidepressant treatment in patients with Major Depressive Disorder: Systematic
review and meta-analysis.
AB - Early improvement of depressive symptoms during the first two weeks of
antidepressant treatment has been discussed to be a resilience signal predicting
a later positive treatment outcome in patients with Major Depressive Disorder
(MDD). However, the predictive value of early improvement varies between studies,
and the use of different antidepressants may explain heterogeneous results. The
objective of this review was to assess the predictive value of early improvement
on later response and remission and to identify antidepressants with the highest
chance of early improvement. We included 17 randomized controlled trials
investigating early improvement in 14,779 adult patients with MDD comparing
monotherapy with an antidepressant against placebo or another antidepressant
drug. 62% (range: 35-85%) of patients treated with an antidepressant and 47%
(range: 21-69%) with placebo were early improver, defined as a >20%/25% symptom
reduction after two weeks of treatment. Early improvement predicted response and
remission after 5-12 weeks of treatment with high sensitivity (85%; 95%-CI: 84.3
to 85.7) and low to moderate specificity (54%; 95%-CI: 53.1 to 54.9). Early
improver had a 8.37 fold (6.97-10.05) higher likelihood to become responder and a
6.38 fold (5.07-8.02) higher likelihood to be remitter at endpoint than non
improver. The highest early improver rates were achieved in patients treated with
mirtazapine or a tricyclic antidepressant. This finding of a high predictive
value of early improvement on treatment outcome may be important for treatment
decisions in the early course of antidepressant treatment. Further studies should
test the efficacy of such early treatment decisions.
PMID- 28697424
TI - Peak exposures to main components of ash and gaseous diesel exhausts in closed
and open ash loading stations at biomass-fuelled power plants.
AB - Fly and bottom ashes are collected at power plants to reduce the environmental
effects of energy production. However, handling the ashes causes health problems
for operators, maintenance workers and truck drivers at the power plants. Hence,
we evaluated ash loaders' peak inhalation exposures to the chemical components of
ash and diesel exhausts in open and closed ash loading stations at biomass
fuelled combined heat and power plants. We also carried out chemical and
morphological analyses of the ashes to evaluate their health hazard potential in
order to find practical technical measures to reduce workers' exposure. On the
basis of X-ray diffraction analyses, the main respirable crystalline ash
compounds were SiO2, CaSO4, CaO, Ca2Al2SiO7, NaCl and Ca3Al2O6 in the fly ashes
and SiO2, KAlSi3O8, NaAlSi3O8 and Ca2Al2SiO7 in the bottom ashes. The short-term
exposure levels of respirable crystalline silica, inhalable inorganic dust, Cr,
Mn, Ni and nitric oxide exceeded their Finnish eight hours occupational exposure
limit values in the closed ash loading station. According to our observations,
more attention should be paid to the ash-moistening process, the use of tank
trucks instead of open cassette flatbed trucks, and the sealing of the loading
line from the silo to the truck which would prevent spreading the ash into the
air. The idling time of diesel trucks should also be limited, and ash loading
stations should be equipped with exhaust gas ventilators. If working conditions
make it impossible to keep to the OEL values, workers must use respirators and
protect their eyes and skin.
PMID- 28697425
TI - Are the TiO2 NPs a "Trojan horse" for personal care products (PCPs) in the clam
Ruditapes philippinarum?
AB - In recent years, increasing quantities of personal care products (PCPs) are being
released into the environment. However, data about bioaccumulation and toxicity
are scarce; and extraction and analytical approaches are not well developed. In
this work, the marine clam Ruditapes philippinarum, selected as model organism,
has been employed to investigate bioaccumulation, antioxidant enzyme activities
and DNA damage due to exposure to TiO2 nanoparticles and bulk TiO2 (inorganic
compounds that are frequent components of PCPs, plastics, paints and coatings,
foods and disinfectant water treatments). We have also studied the joint effect
of both forms of inorganic TiO2 combined with four organic compounds (mixture
exposures) commonly used in PCPs: an antimicrobial (triclosan), a fragrance
(OTNE) and two UV filters (benzophenone-3 and octocrylene). Bioaccumulation of
the inorganic compound, TiO2, was almost immediate and constant over exposure
time. With respect to the organic compounds in mixtures, they were mediated by
TiO2 and bioaccumulation is driven by reduced size of the particles. In fact,
nanoparticles can be considered as a vector to organic compounds, such as
triclosan and benzophenone-3. After a week of depuration, TiO2 NPs and TiO2 bulk
in clams showed similar levels of concentration. Some organic compounds with
bioactivity (Log Kow >3), like OTNE, showed low depuration after one week. The
joint action of the organic compound mixture and either of the two forms of TiO2
provoked changes in enzyme activity responses. However, for the mixtures, DNA
damage was found only after the depuration period.
PMID- 28697426
TI - Dimension-dependent toxicity of silver nanomaterials on the cladocerans Daphnia
magna and Daphnia galeata.
AB - Silver nanomaterials (AgNMs) are widely used in many fields because of their
antimicrobial properties. Depending on the shapes and dimensions of the AgNMs,
their potential uses and needs vary. Consequently, vast quantities of multi
dimensional AgNMs are being manufactured and released into aquatic ecosystems,
where they have toxic effects on aquatic organisms. Therefore, an assessment of
the toxicities of each multi-dimensional AgNM on aquatic ecosystems is necessary.
In this study, important aquatic model species, Daphnia magna and Daphnia
galeata, were used to assess and compare the toxic effects of silver ions (Ag+
ions) and multi-dimensional AgNMs, including silver nanoparticles (AgNPs), silver
nanowires (AgNWs), and silver nanoplates (AgPLs). The results indicated that Ag+
ions were more toxic than AgNMs of different dimensions and sizes, and that AgPLs
were the most toxic of the AgNMs. In the case of AgNWs, the longer (20 MUm)
nanowire was more toxic than the shorter (10 MUm) one. In addition, D. galeata
was more sensitive than D. magna to both Ag+ ions and AgNMs. This study
elucidates the dimension-dependent toxicity of and silver ions and nanomaterials
in the cladocerans D. magna and D. galeata. Further studies will be necessary to
further elucidate the actual risk of multi-dimensional nanomaterials in
ecosystems.
PMID- 28697427
TI - NMR-based metabolomic study on the toxicological effects of pesticide, diazinon
on adaptation to sea water by endangered Persian sturgeon, Acipenser persicus
fingerlings.
AB - NMR-based metabolomics was applied to explore metabolic impacts of diazinon on
sea water adaptation of Persian sturgeon fingerlings, Acipenser persicus.
Fingerlings were exposed to sub-lethal concentrations of diazinon in freshwater
(FW) for 96 h (short-term trial) and 12 days (long-term trial) and then exposed
in brackish water (BW) (12 mg L-1 salinity) for 24 h. After 96 h and 12 days
exposure in FW, identified metabolites (amino acids, osmolytes, energy
metabolites) showed different change-patterns compared to control group (P <
0.05) as follow: (A) short-term trial: higher plasma levels of glucose, lactate
(in all diazinon-exposed fish), acetate and acetoacetate (in 0.9 mg L-1diazinon
treatment); lower levels of creatine (in all diazinon-exposed fish),
trimethylamine-N-oxide, choline, taurine, betaine, N,N-dimethylglycine and almost
all amino acids in fish exposed to high concentrations of diazinon (0.54 and 0.9
mg L-1 diazinon). (B) Long-term trial: higher plasma levels of lipid oxidation
metabolites and almost all amino acids in fish exposed to 0.54 and 0.9 mg L-1
diazinon; lower levels of creatine, trimethylamine-N-oxide, N,N-dimethylglycine,
betaine, choline (in all diazinon-exposed fish), glucose (in 0.54 and 0.9 mg L
1diazinon treatments) and taurine (in 0.9 mg L-1 diazinon treatment). When fish
were exposed in BW for 24 h, the plasma levels of osmolytes decreased
significantly in almost all experimental groups of short-term and long-term trial
(P < 0.05). In short-term trial, the plasma levels of glucose in all groups and
lactate in 0.18 and 0.54 mg L-1 diazinon treatments increased after salinity
challenge (P < 0.05). However, a significant decrease was observed in lactate
levels in 0.9 mg L-1 diazinon treatment (P < 0.05). Also, the plasma levels of
amino acids decreased mostly in fish of control group than exposed fish (P <
0.05). The plasma glycerol concentration showed a significant decrease only in
fish of 0.54 mg L-1 diazinon treatment (P < 0.05). In long term trial, the
energetic metabolites (acetate, acetoacetate, glycerol) showed significant
increases mostly in fish exposed to high concentrations of diazinon (P < 0.05).
Phosphocreatine was detected only in groups exposed to 0.54 and 0.9 mg L-1
diazinon. Some amino acids decreased in control and diazinon-exposed groups while
glycine (in control and 0.18 mg L-1 diazinon treatment), glutamine and alanine
(in 0.9 mg L-1 diazinon treatment) elevated significantly after 24 h acclimation
in BW (P < 0.05). Our results may help to understand the effects of pesticides on
fish osmoregulation from a metabolic approach.
PMID- 28697428
TI - Temporal and spatial variation of polychlorinated biphenyls (PCBs) contamination
in environmental compartments of highly polluted area in Central Russia.
AB - This study highlights the fact that serious contamination from polychlorinated
biphenyls (PCBs) still exists in Serpukhov City (Russia). The research help to
determine the temporal (16- and 24-year periods) and spatial PCBs distribution in
the environmental compartments of the studied region. Samples of soil, sediments,
water and plants were analysed in order to establish their contamination levels.
The most recent data on the Serpukhov City's soil contamination showed that the
PCBs concentrations varies from 0.0009 to 1169 mg/kg depending on the sampling
point and the distance from the pollution source. The temporal trends of the
contamination distribution with the soil depth showed contamination migration in
the upper soil layers of the highly polluted site. The high level of water
pollution (11.5 MUg/L) in the proximity to the contamination source and the
sediments contamination (0.098-119 mg/kg) were determined, as well as the water
migration pathways of the PCBs that were prevalent in the studied region. The PCB
congener group (by the level of chlorination) analysis showed that
heptachlorinated biphenyls were only found in the soils in close proximity to the
contamination place, while biphenyls with Cl <= 6 were found in the soil samples
downstream of the condenser plant and with Cl <= 5 in the soil samples upstream
of the plant. The plant uptake of PCBs, even on the extremely contaminated site,
was shown. In turn, this research present new knowledge necessary for the
development of a contaminated territory remediation strategy.
PMID- 28697429
TI - Bisphenol A disrupts steroidogenesis and induces a sex hormone imbalance through
c-Jun phosphorylation in Leydig cells.
AB - Bisphenol A (BPA) is a well-known endocrine disrupting chemical (EDC) that is
used to manufacture plastic consumer products. It is well known that exposure to
BPA can induce defects in gonad development and negatively influences
reproductive function in both males and females. In this study, we assessed the
effects of BPA on hormone production in Leydig cells, which secrete hormones in
the testes and support male fertility. We examined two steroidogenic enzymes,
CYP11A1 and CYP19 that involved in sex hormone synthesis in mouse MA-10 Leydig
cells. We found that BPA activated CYP gene in both mRNA and protein levels then
resulted in alteration of the normal sex hormone ratio. Furthermore, we found
that BPA induced c-Jun phosphorylation and contributed to CYP gene expression.
Similar results were observed in an animal study. In conclusion, BPA disrupts the
hormone environment in testis via steroidogenic gene activation through the JNK/c
Jun signaling pathway.
PMID- 28697430
TI - Evaluation of natural organic matter adsorption on Fe-Al binary oxide: Comparison
with single metal oxides.
AB - The adsorption characteristics of three types of standard natural organic matter
(NOM) on iron-aluminum (Fe-Al) binary oxide (FAO) and heated aluminum oxide (HAO)
under natural surface water condition were investigated using various adsorption
isotherms and kinetic models. FAO was synthesized by Fe oxide and Al oxide, mixed
using the sol-gel hydrothermal method, and aluminum sulfate was used to make HAO.
The amount of adsorbed NOM was increased to 79.6 mg g-1 for humic acid (HA),
101.1 mg g-1 for sodium alginate (SA) in the FAO, but the maximum adsorption
capacity of bovine serum albumin (BSA) (461.3 mg g-1) was identified on the HAO.
The adsorption of HA, BSA, and SA dramatically increased (>70%) on FAO in 5 min
and HA was significantly removed (90%) among the three NOM. Mutual interaction
among the adsorbed NOM (BSA) occurred on the HAO surface during adsorption due to
formation of monolayer by protein molecules at neutral pH. The pseudo second
order clearly represented the adsorption kinetics for both adsorbents. The
equilibrium isotherm data of FAO was better exhibited by the Langmuir isotherm
model than by the Freundlich isotherm, but HAO was a slightly non-linear Langmuir
type. Also, the free energy, enthalpy, and entropy of adsorption were determined
from the thermodynamic experiments. Adsorption on FAO was spontaneous and an
exothermic process. Fluorescence excitation-emission matrix (FEEM) spectra were
used to elucidate the variation in organic components. The results obtained
suggests that the significant changes in the surface property of the adsorbent
(large surface area, increased crystalline intensity, and fine particle size)
were effectively determined by the Fe-synthesized Al oxide mixed using the sol
gel hydrothermal method. The results also suggest that the changes enhanced the
adsorption capacity, whereby three NOM were notably removed on FAO regardless of
NOM characteristics (hydrophobic and hydrophilic).
PMID- 28697431
TI - Phytotoxicity assessment of olive mill solid wastes and the influence of phenolic
compounds.
AB - The main objective of this work is to evaluate the phytotoxicity of olive mill
solid wastes (OMW) produced in two different centrifugation technologies and also
the toxicity associated with specific phenolic compounds. Two samples of waste
were collected in two-phase (2P-OMW) and three-phase (3P-OMW) centrifugation
olive oil production processes, and cress bioassays with Lepidium sativum L. were
employed to evaluate phytotoxicity. Although both OMW have similar total phenolic
content (TPh), results confirmed that 2P-OMW is more phytotoxic than 3P-OMW. When
extracts from 2P-OMW at liquid to solid ratio of 10 L kg-1 were applied none of
the seeds germinated, i.e. germination index (GI) was 0%, while for 3P-OMW GI was
94.3%. Growth tests in soil and mixtures with OMW also led to more favorable
results for 3P-OMW, whereas worse results than those obtained in the control
experiments were observed. In order to discriminate the individual influence of
eleven phenolic compounds, gallic acid, protocatechuic acid, cinnamic acid,
syringic acid, 3,4,5-trimethoxybenzoic acid, 4-hydroxybenzoic acid, vanillic
acid, p-coumaric acid, caffeic acid, veratric acid and phenol were tested in the
concentration range of 5-500 mg L-1. Results showed that cinnamic acid is the
most phytotoxic, with EC50 of 60 mg L-1, which is related with its
hydrophobicity. Moreover, increasing -OH and -OCH3 groups in these molecules seem
to reduce phytotoxicity. Tests with a mixture of six phenolic compounds
demonstrated there are neither synergistic nor additive effects. The
phytotoxicity appears to be determined by the presence of the most lipophilic
phenolic molecule.
PMID- 28697432
TI - Racial and ethnic disparities in the healing of pressure ulcers present at
nursing home admission.
AB - BACKGROUND: Pressure ulcers increase the risk of costly hospitalization and
mortality of nursing home residents, so timely healing is important. Disparities
in healthcare have been identified in the nursing home population but little is
known about disparities in the healing of pressure ulcers. PURPOSE: To assess
racial and ethnic disparities in the healing of pressure ulcers present at
nursing home admission. Multi-levels predictors, at the individual resident,
nursing home, and community/Census tract level, were examined in three large data
sets. METHODS: Minimum Data Set records of older individuals admitted to one of
439 nursing homes of a national, for-profit chain over three years with a stages
2-4 pressure ulcer (n=10,861) were searched to the 90-day assessment for the
first record showing pressure ulcer healing. Predictors of pressure ulcer healing
were analyzed for White admissions first using logistic regression. The Peters
Belson method was used to assess racial or ethnic disparities among minority
group admissions. RESULTS: A significantly smaller proportion of Black nursing
home admissions had their pressure ulcer heal than expected had they been part of
the White group. There were no disparities in pressure ulcer healing
disadvantaging other minority groups. Significant predictors of a nonhealing of
pressure ulcer were greater deficits in activities of daily living and pressure
ulcer severity. CONCLUSIONS: Reducing disparities in pressure ulcer healing is
needed for Blacks admitted to nursing homes. Knowledge of disparities in pressure
ulcer healing can direct interventions aiming to achieve equity in healthcare for
a growing number of minority nursing home admissions.
PMID- 28697433
TI - Lack of an association between the aPKClambda/iota expression in prostate cancer
and the patient outcomes.
PMID- 28697434
TI - Modelling of compressible and orthotropic surgical mesh implants based on optical
deformation measurement.
AB - There is a potential mismatch between surgical mesh implants for hernia repair of
pelvic floor surgery and the host tissue because soft tissue is incompressible
and meshes are compressible. Therefore, mesh and tissue may develop different
stiffness over the range of deformation. In addition compressibility is related
to a change of porosity of the mesh which may decrease during the deformation.
Scar formation and the ingrowth of the mesh can be related to effective porosity
which decreases discontinuously in uniaxial loading at a critical stretch when
pore areas collapse and therefore the mesh becomes ineffective. Compressibility
requires several non standard approaches which can be performed with high
accuracy and local resolution by deformation measurement with digital image
correlation (DIC). A compressible hyperelastic model is chosen and identified
with biaxial deformation measurements. Also effective porosity of deformed meshes
can be calculated on the basis of biaxial deformation. The proposed constitutive
equation and the developed model of effective porosity are represented in form of
principle stretch. Stretch can be measured with magnetic resonance imaging (MRI)
visible meshes so that stress and effective porosity can be derived in vivo.
PMID- 28697435
TI - Comparative analysis of poly-glycolic acid-based hybrid polymer starter matrices
for in vitro tissue engineering.
AB - Biodegradable scaffold matrixes form the basis of any in vitro tissue engineering
approach by acting as a temporary matrix for cell proliferation and extracellular
matrix deposition until the scaffold is replaced by neo-tissue. In this context
several synthetic polymers have been investigated, however a concise systematic
comparative analyses is missing. Therefore, the present study systematically
compares three frequently used polymers for the in vitro engineering of
extracellular matrix based on poly-glycolic acid (PGA) under static as well as
dynamic conditions. Ultra-structural analysis was used to examine the polymers
structure. For tissue engineering (TE) three human fibroblast cell lines were
seeded on either PGA-poly-4-hydroxybutyrate (P4HB), PGA-poly-lactic acid (PLA) or
PGA-poly-caprolactone (PCL) patches. These patches were analyzed after 21days of
culture qualitative by histology and quantitative by determining the amount of
DNA, glycosaminoglycan and hydroxyproline. We found that PGA-P4HB and PGA-PLA
scaffolds enhance tissue formation significantly higher than PGA-PCL scaffolds
(p<0.05). Polymer remnants were visualized by polarization microscopy. In
addition, biomechanical properties of the tissue engineered patches were
determined in comparison to native tissue. This study may allow future studies to
specifically select certain polymer starter matrices aiming at specific tissue
properties of the bioengineered constructs in vitro.
PMID- 28697436
TI - Fe3O4 nanoparticles modified by CD-containing star polymer for MRI and drug
delivery.
AB - Fe3O4 nanoparticles with ultrasmall sizes show good T1 or T1+T2 contrast
abilities, and have attracted considerable interest in the field of magnetic
resonance imaging (MRI) contrast agents. For effective biomedical applications,
the colloidal stability and biocompatibility of the Fe3O4 nanoparticles need to
be improved without reducing MRI relaxivity. In this paper, star polymers were
used as coating materials to modify Fe3O4 nanoparticles in view of their dense
molecular architecture with moderate flexibility. The star polymer was composed
of a beta-cyclodextrin (beta-CD) core and poly(2-(dimethylamino) ethyl
methacrylate) (PDMAEMA) arms. Meanwhile, reduced glutathione (GSH), as a model
drug, was also associated with the star polymer. Thus, a new platform for
simultaneous diagnosis and treatment was achieved. Compared to the Fe3O4
nanoparticles coated with linear polymers, the Fe3O4 nanoparticles coated with
star polymers (Fe3O4@GCP) possessed higher GSH association capacity and better
stability in serum-containing solution. GSH could be released from Fe3O4@GCP
nanoparticles in response to pH value of the solution. Since the sulfhydryl group
on GSH is able to combine free radicals, Fe3O4@GCP nanoparticles exhibited less
cytotoxicity compared to the Fe3O4 nanoparticles without including GSH.
Furthermore, the nanoparticles could also serve as good T1 MRI contrast agent,
and the MRI relaxivity of Fe3O4@GCP nanoparticles did not decrease after coated
with the star polymer. These results indicate that the precisely designed
Fe3O4@GCP nanoparticles could be used as a versatile promising theranostic nano
platform.
PMID- 28697437
TI - Novel ex vivo protocol using porcine vagina to assess drug permeation from
mucoadhesive and colloidal pharmaceutical systems.
AB - Local treatment of vaginal diseases presents advantages over systemic treatments
and the interaction of the drug delivery systems with the biological tissue is a
key factor for a successful vaginal topical therapy. Conventional protocols for
permeation studies have high variability and fail in distinguishing drug
penetration from mucoadhesive or colloidal drug delivery systems from
conventional formulations, as tissue interaction is normally under estimated. The
protocol presented in this paper is a simplified ex vivo vertical model, in which
formulations are placed in hung porcine vaginas with the objective of mimicking a
condition closer to the biological circumstance, specifically considering the
possible leak from the vaginal canal in the vertical position. The results
indicate the proposed method was capable of differentiating formulations
performances and histological evaluation showed mucosa structures are preserved
during this new assay. Therefore, the ex vivo method can be considered reliable
for approaching the physiological situation in comparative studies.
PMID- 28697438
TI - Assessment of the correlation among antibiotic resistance, adherence to abiotic
and biotic surfaces, invasion and cytotoxicity of Pseudomonas aeruginosa isolated
from diseased gilthead sea bream.
AB - Improper uses of antibiotics to treat fish disease pose an increase of multidrug
resistance in Pseudomonas aeruginosa. In order to escape host antimicrobial
agents and induce cytotoxicity, different virulence properties are needed by
these bacteria such as, biofilm formation, adhesion and invasion ability. This
study was conducted to isolate Pseudomonas aeruginosa from diseased cultured
gilthead sea bream. Seventeen isolates of Pseudomonas aeruginosa were identified
by PCR. All of the isolates tested were susceptible to Gentamicin and
Ciprofloxacin. Highest level of resistance was observed against Erythromycin,
Ampicillin and Tetracycline. Among the 17 isolates, 11 showed multi-drug
resistance. The isolates were screened for biofilm formation in abiotic surfaces,
adherence, invasion and cytotoxicity against Hep-2 cells. We found that some
strains were able to adhere to abiotic and biotic surface and to enter inside Hep
2 cells. Using cytochalasin D inhibitor, we observed a significant decrease in
invasion of epithelial cells. The 17 washed bacterial cells induce variable
degree of cytotoxicity. However, no cytotoxic effects on Hep-2 cells were
obtained among the totality of cell free filtrate of Pseudomonas strains. By
studying the relationship between different virulence properties, a significant
positive correlation was obtained between both biofilm formation and adherence,
and between adherence and invasion to epithelial cells. Subsequently, we found
that the mean values of adhesion and invasion in the MDR group were significantly
higher than those observed in the non-MDR group. Likewise, a significant positive
correlation was found among adhesive and invasive capacities of Pseudomonas
strains and their antibiotic resistance phenotypes.
PMID- 28697439
TI - Targeting dendritic cells for the treatment of autoimmune disorders.
AB - In the last decades, it has been recognized that extracellular vesicles (EVs) are
not only cell debris with no biological role, but instead they play a key role in
information exchange between cells either in health and disease conditions. EVs
exhibit indeed their biological role in a pleiotropic manner. They can modulate
immune responses through the activation, transfer or removal of surface receptors
on target cells, the removal of cytolytic components such as membrane attack
complexes, and the transfer of signaling molecules/effectors, such as nucleic
acid species, infectious particles, and oncogenes. Among the naturally-derived
nanoparticles that have been developed in the last years, stimuli responsive
exosomes drew special attention since they intrinsically possess many attributes
of a desirable drug delivery system. Their small size allows them to bypass the
mononuclear phagocytic system (MPS) clearance, thereby prolonging their
circulation time for passive targeting to inflammatory tissues. Moreover, they
can deliver their cargo directly into the cytosol, avoiding the
lysosomal/endosomal pathway and thus, increasing the transfection efficiency when
they are used as gene delivery systems. of This review offers the state of the
art knowledge on the physiology and properties of EVs, namely, apoptotic
vesicles, microvesicles and exosomes as innovative drug delivery systems for gene
therapy, with a special focus on targeting dendritic cells for the treatment of
autoimmune disorders.
PMID- 28697440
TI - Electrochemical nucleic acid detection based on parallel structural
dsDNA/recombinant azurin hybrid.
AB - Several challenges remained to fabricate a molecular-level nucleic acid biosensor
such as surface immobilization control, single mismatch detection and low current
response. To overcome those issues, for the first time, authors presented a novel
parallel structural dsDNA/recombinant azurin (PSD/rAzu) hybrid structure for the
general nucleic acid detection. The PSD was designed and introduced by the
optimized 8 Ag+ ions to have greater conductivity than the canonical dsDNA, and
conjugated with rAzu to develop a general platform for electrochemical detection
of miRNAs and viral DNAs with high reproducibility and ultra-sensitivity towards
single base pair mutation. Thanks to the bifunctional rAzu as the selective
spacer and electrochemical signal mediator, in the presence of the target strand,
the imperfect PSD switched rapidly to the upright position where the Ag+ ions
intercalated between C-C mismatches of dsDNAs at the top of each structure
brought further from the electrode surface resulting in a significant
electrochemical signal drop of the Ag+ ions. The charge transfer (CT) mechanism
across the hybrid structure was simply clarified on the basis of the redox
potential location of the species. The electrical conductivity of DNAs were
measured using scanning tunneling spectroscopy (STS) at the molecular scale and
cyclic voltammetry (CV) technique based on the reduction of Ag+ ion. The proposed
PSD/rAzu hybrid structure with a great capability of single mutation recognition
and miRNA expression level profiling in cancer cells holds a very promising
platform to be studied for further development of various kinds of nanoscale
biosensors, bioelectronic devices.
PMID- 28697441
TI - A novel molecularly imprinted electrochemical sensor modified with carbon dots,
chitosan, gold nanoparticles for the determination of patulin.
AB - In this paper, molecular imprinting technique was applied to the electrochemical
sensor. We used 2-oxindole as dummy template, rho-Aminothiophenol (rho-ATP) as
functional monomers, combined with the high sensitivity of electrochemical
detection, to achieve a specific and efficient detection of patulin in fruit
juice. In addition, carbon dots and chitosan were used as the modifying material
to improve electron-transfer rate, expand the electroactive surface of glassy
carbon electrode and enhance strength of the signal. The Au-S bond and hydrogen
bond were employed to complete the assembly of the rho-ATP and 2-oxindole on the
surface of the electrode. Then, polymer membranes were formed by
electropolymerization in a polymer solution containing rho-ATP, HAuCl4,
tetrabutylammonium perchlorate (TBAP) and the template molecule 2- oxindole.
After elution, the specific cavity can adsorb the target patulin. Cyclic
voltammetry (CV) and differential pulse voltammetry (DPV) measurements were
performed to monitor the electropolymerization process and its optimization.
Transmission electron microscopy (TEM), Scanning electron microscopy (SEM) and
Atomic force microscopy (AFM) analyses were used for characterization. This was
the first time that the molecularly imprinted polymer (MIP) technology combined
with carbon dots, chitosan and Au nanoparticles modification and was applied in
the electrochemical detection of patulin. The linear response range of the MIP
sensor was from 1 * 10-12 to 1 * 10-9molL-1 and the limit of detection (LOD) was
7.57 * 10-13molL-1. The sensor had a high-speed real-time detection capability,
low sample consumption, high sensitivity, low interference, good stability and
could become a new promising method for the detection of patulin.
PMID- 28697442
TI - Portable amperometric immunosensor for histamine detection using Prussian blue
chitosan-gold nanoparticle nanocomposite films.
AB - Histamine (HA) is a biogenic amine that can accumulate to high concentration
levels in food as a result of microbial activity and can cause toxic effects in
consumers. In this work, a portable electrochemical immunosensor capable of
detecting HA with high sensitivity and selectivity was developed. Prussian blue
chitosan-gold nanoparticle (PB-CS-AuNP) nanocomposite films with excellent
biocompatibility were synthesized and characterized by scanning electron
microscopy and energy dispersive X-ray analysis. The PB-CS-AuNP were coated onto
a screen-printed electrode by one-step electrodeposition and used to conjugate
the HA ovalbumin conjugate (HA-Ag). HA was determined by a competition between
the coating HA-Ag and the HRP labeled HA antibody (HRP-HA-Ab). After careful
optimization of assay conditions and Box-Behnken analysis, the developed
immunosensor showed a linear range from 0.01 to 100MUg/mL for HA in fish samples.
The average recoveries from spiked samples ranged from 97.25% to 105%. The
biosensor also showed good specificity, reproducibility, and stability,
indicating its potential application in monitoring HA in a simple and low cost
manner.
PMID- 28697443
TI - Selective binding of Pb2+ with manganese-terephthalic acid MOF/SWCNTs:
Theoretical modeling, experimental study and electroanalytical application.
AB - A nanocomposite of flake-shaped manganese-terephthalic acid MOF/single-walled
carbon nanotubes (Mn(TPA)-SWCNTs) was synthesized using manganese chloride,
terephthalic acid and SWCNTs as raw materials. Theoretical modeling study shows
that the Mn(TPA) component has stronger adsorption ability to lead ion (Pb2+)
than the other common heavy metal ions, which is in good agreement with the
result of electrochemical assay. Then, the Mn(TPA)-SWCNTs were used as a sensing
matrix for the voltammetric determination of Pb2+. The results displayed that the
sensor shows high analytical performance for Pb2+ due to the synergy of Mn(TPA)
with highly selective binding to Pb2+ and SWCNTs with high electronic
conductivity. Under the optimal conditions, the Mn(TPA)-SWCNTs-based
electrochemical sensor presented a wide linear response over the concentration
range from 0.10 to 14.0MUM. The limit of detection was achieved to be 38nM.
Satisfactory results were also achieved when the Mn(TPA)-SWCNTs-based sensor was
utilized for the determination of Pb2+ in the practical samples of industrial
wastewater and human serum, suggesting great promising of the sensor for
practical application.
PMID- 28697444
TI - An efficient electrochemiluminescence amplification strategy via bis-co-reaction
accelerator for sensitive detection of laminin to monitor overnutrition
associated liver damage.
AB - With the world wildly improvement in dietary and nutrition status, it couldn't be
ignored that the chronic liver disease (CLD) resulted from the overnutrition. In
order to estimate nutrition status for healthy living, an efficient and sensitive
electrochemiluminescence (ECL) sandwich immunosensor of laminin (LN), a marker of
CLD, was proposed for early diagnosis of CLD. In this work, the anodic ECL
behavior of perylene derivative using H2O2 as co-reactant was demonstrated and
the possible ECL mechanism was proposed. Furthermore, a significantly amplified
ECL response could be obtained via Ag and Fe-Fe2O3 nanoparticles as bis-co
reaction accelerator. As a result, the proposed ECL immunosensor performed good
sensitivity and accuracy with a detection limit down to 0.03pg/mL. Moreover, this
immunosensor was successfully employed to monitor patient serum, which exhibited
an alternative avenue for the early diagnosis of other diseases via proteins,
nucleotide sequence, microRNA and cells.
PMID- 28697445
TI - An ultrasensitive bioluminogenic probe of gamma-Glutamyltranspeptidase in vivo
and in human serum for tumor diagnosis.
AB - Abnormal expression of gamma-Glutamyltranspeptidase (GGT) in living organisms is
closely implicated in the development of several human tumors. The GGT levels in
tissue and serum have emerged as a potential criterion for tumor diagnosis.
However, precise "light up" GGT activity in vivo is still challenging due to the
signal interferes of background. Bioluminescence based on the firefly luciferase
catalyzed reaction for light production provides a feasible strategy for GGT
detection in vivo. In this report, a bioluminogenic probe, Glu-Luc, was designed
and synthesized by connecting D-luciferin with gamma-glutamyl group. The cleavage
of gamma-glutamyl group is triggered by GGT, resulting in the release of D
luciferin, which generates a bright bioluminescence emission in the present of
luciferase and ATP. The probe exhibits very high selectivity and sensitivity
toward GGT activity from in vitro to in vivo and in clinical samples, which
offers a promising tool for investigations of the GGT-overexpressing related
biological process including tumor diagnosis and prognosis in living organisms.
PMID- 28697446
TI - Electrochemical peptide sensor for diagnosing adenoma-carcinoma transition in
colon cancer.
AB - Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths.
Therefore, more sensitive and early diagnostic methods for CRC are urgently
needed. In this study, an efficient electrochemical biosensor for early diagnosis
of adenoma-to-carcinoma progression that employs a series of chemically modified
affinity peptides was developed. A series of amino acid-substituted and cysteine
incorporated synthetic peptides with flexible linkers was chemically synthesized
and immobilized to a gold sensor layer; performance of the sensor was monitored
using cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS).
Potential affinity peptides (LRG1 BP1-BP4) specific for the LRG1 biomarker as a
target protein were chosen according to a quantitative current decrease and
dynamic impedance increase by CV and EIS, respectively. Using EIS, the Kd value
of the LRG1 BP3 peptide was found to be 8.3 +/- 2.7nM. The applicability of the
sensor to detect LRG1 proteins was confirmed in human plasma from colorectal
adenomas and carcinomas (n = 20 in each group). The detection of LRG1 in
accordance with the DeltaRct value (electron-transfer resistance at the electrode
surface) of the sensor layer incorporating LRG1 BP3 peptides showed a
statistically significant difference (p < 0.001) between adenomas and carcinomas,
indicating that the potential use of this biosensing platform for detecting the
CRC biomarker, as well as for monitoring the colorectal adenoma-to-carcinoma
transition in an electrochemically miniaturized biosensor (e-chem biosensor) in
point-of-care testing, is possible.
PMID- 28697447
TI - Dynamical regimes of lipids in additivated liposomes with enhanced elasticity: A
field-cycling NMR relaxometry approach.
AB - We study the molecular dynamics of lipids in binary large unilamellar liposomes
suspended in D2O composed of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC)
or soy phosphatidylcholine (SPC) additivated with different percentiles of sodium
deoxycholate (SDC). We use the fast field-cycling proton NMR relaxometry
technique over a wide timescale and at diverse temperatures. A model previously
validated in different formulations is here employed for the relaxometric
analysis of elastic vesicles. A new dynamical regime is observed for the first
time in additivated DMPC and additivated/non-additivated SPC liposomes. This
surprising feature is discussed in terms of vesicle shape fluctuations, enhanced
elasticity and lipid & additive diffusion within the membrane. The continuum
elastic theory is revisited for a better understanding of recent experiments and
those here presented. We address the point of deformability measurements across
rigid permeable barriers versus measurements of the bending elastic modulus in
free-standing vesicles.
PMID- 28697448
TI - In silico analyses of the effects of a point mutation and a pharmacological
chaperone on the thermal fluctuation of phenylalanine hydroxylase.
AB - Phenylketonuria (PKU) is an inborn error of phenylalanine metabolism due to
mutations in phenylalanine hydroxylase (PAH). Recently, small compounds, known as
pharmacological chaperones (PhCs), have been identified that restore the
enzymatic activity of mutant PAHs. Understanding the mechanism of the reduction
in enzymatic activity due to a point mutation in PAH and its restoration by PhC
binding is important for the design of more effective PhC drugs. Thermal
fluctuations of an enzyme can alter its activity. Here, molecular dynamics
simulation show the thermal fluctuation of PAH is increased by introduction of
the A313T mutation. Moreover, a simulation using the A313T-PhC complex model was
also performed. Thermal fluctuation of the mutant was found to be reduced upon
PhC binding, which contributes to restoring its enzymatic activity.
PMID- 28697449
TI - Binding kinetics of mutant p53R175H with wild type p53 and p63: A Surface Plasmon
Resonance and Atomic Force Spectroscopy study.
AB - The oncogenic mutant p53R175H, one of the most frequently occurring in human
cancers and usually associated with poor prognosis and chemo resistance, can
exert a dominant negative effect over p53 family members, namely wild type p53,
p63 and p73, inhibiting their oncosuppressive function. Novel anticancer
strategies based on drugs able to prevent the formation of complexes between
p53R175H and the p53 family members call for a deeper knowledge on the molecular
mechanisms of their interaction. To this aim, p53R175H/p63 and p53R175H/p53
complexes were investigated in vitro by using Surface Plasmon Resonance and
Atomic Force Spectroscopy, two emerging and complementary techniques able to
provide interaction kinetic information, in near physiological conditions and
without any labelling. Both approaches show that p53R175H forms a very specific
and highly stable bimolecular complex with both p63 and p53; with these
interactions being characterized by a very high affinity with equilibrium
dissociation constant, KD, of about 10-9M. These kinetics results, discussed also
in connection with those previously reported for the interaction of p53R175H with
p73, could inspire the design of suitable anticancer drugs able to antagonize the
interaction of p53R175H with the p53 family members, by restoring then their anti
tumour function.
PMID- 28697450
TI - Changes in genetically drifted H3N2 influenza A viruses and vaccine effectiveness
in adults 65 years and older during the 2016/17 season in Denmark.
AB - BACKGROUND: In Denmark, influenza A virus of the subtype H3N2 has been dominating
the 2016/17 season, as in most countries of the Northern Hemisphere. OBJECTIVES:
This study was conducted as part of the Danish seasonal influenza surveillance
programme to genetically characterize circulating H3N2 viruses and determine the
seasonal vaccine effectiveness (VE) overall in the Danish population and further
on the virus cluster level. STUDY DESIGN: Influenza virus positive samples
submitted for the national surveillance programme were genetically characterized
by sequencing. VE estimates against influenza A and the circulating virus
clusters were determined in patients above 65 years using the test-negative case
control design. RESULTS: The genetic characterization revealed several
genetically drifted viruses, which could be divided into four main clusters by
the defining amino acid substitutions: 3C.2a/N121K/S144K, 3C.2a/T131K/R142K,
3C.2a1, and 3C.2a1/N121K. Some of the drifted viruses appeared to be more
prominent in vaccinated or non-vaccinated individuals, respectively. Overall the
adjusted VE was 7.4% (95% confidence interval (CI): -6.0-19.2) among inpatients
and 19.3% (95% CI: -5.7-38.4) among outpatients, respectively. VE for the four
main virus clusters was; cluster 3C.2a1: 38.8% (95% CI: -29.8-71.1), cluster
3C.2a/N121K/S144K: 9.2% (95% CI: -63.0-49.4), cluster 3C.2a/T131K/R142K: 19.0%
(95% CI: -85.3-64.6), and cluster 3C.2a1/N121K: -12.2% (95%CI: -129.7-45.2).
CONCLUSIONS: Several genetically drifted H3N2 viruses have been circulating in
Denmark in the 2016-17 influenza season. An overall low VE was estimated and VE
for the four main virus cluster indicate different VEs between the circulating
drifted H3N2 viruses.
PMID- 28697451
TI - Reduced efficacy of albendazole against Ascaris lumbricoides in Rwandan
schoolchildren.
AB - Control of human soil-transmitted helminths (STHs) relies on preventive
chemotherapy of schoolchildren applying the benzimidazoles (BZ) albendazole or
mebendazole. Anthelmintic resistance (AR) is a common problem in nematodes of
veterinary importance but for human STHs, information on drug efficacy is limited
and routine monitoring is rarely implemented. Herein, the efficacy of single dose
albendazole (400 mg) was evaluated in 12 schools in the Huye district of Rwanda
where Ascaris is the predominant STH. Ascaris eggs were detected by wet mount
microscopy and the Mini-FLOTAC method to assess cure rate (CR) and faecal egg
count reduction (FECR). Blood and faecal samples were analysed for co-infections
with Plasmodium sp. and Giardia duodenalis, respectively. Ascaris positive
samples collected before and after treatment were analysed for putatively BZ
resistance associated beta-tubulin gene single nucleotide polymorphisms. The
overall CR was 69.9% by Mini-FLOTAC and 88.6% by wet mount microscopy. The FECR
was 75.4% and the 95% calculated confidence intervals were 50.4-87.8% using
sample variance, 55.4-88.8% by bootstrapping, and 75.0-75.7% applying a Markov
Chain Monte Carlo Bayesian approach. FECR varied widely between 0 and 96.8% for
individual schools. No putative BZ-resistance associated polymorphisms were found
in the four Ascaris beta-tubulin isotype genes examined. Since FECRs <95%
indicate reduced efficacy, these findings raise the suspicion of BZ resistance.
In the absence of respective molecular evidence, heritable AR in the local
Ascaris populations cannot be formally proven. However, since FECRs <95% indicate
reduced efficacy, BZ resistance may be suspected which would be alarming and
calls for further analyses and routine monitoring in preventive chemotherapy
programs.
PMID- 28697452
TI - Effect of fluoride exposure on mRNA expression of cav1.2 and calcium signal
pathway apoptosis regulators in PC12 cells.
AB - This study investigated the effects of fluoride exposure on the mRNA expression
of Cav1.2 calcium signaling pathway and apoptosis regulatory molecules in PC12
cells. The viability of PC12 cell receiving high fluoride (5.0mM) and low
fluoride (0.5mM) alone or fluoride combined with L-type calcium channel (LTCC)
agonist/inhibitor (5umol/L FPL6417/2umol/L nifedipine) was detected using cell
counting kit-8 at different time points (2, 4, 6, 8, 12, 10, and 24h). Changes in
the cell configuration were observed after exposing the cells to fluoride for
24h. The expression levels of molecules related to the LTCC were examined,
particularly, Cav1.2, c-fos, CAMK II, Bax, and Bcl-2. Fluoride poisoning induced
severe cell injuries, such as decreased PC12 cell activity, enhanced cell
apoptosis, high c-fos, CAMKII, and Bax mRNA expression levels. Bcl-2 expression
level was also reduced. Meanwhile, high fluoride, high fluoride with FPL64176,
and low fluoride with FPL64176 enhanced the Cav1.2 expression level. In contrast,
low fluoride, high fluoride with nifedipine, and low fluoride with nifedipine
reduced the Cav1.2 expression level. Thus, Cav1.2 may be an important molecular
target for the fluorosis treatment, and the LTCC inhibitor nifedipine may be an
effective drug for fluorosis.
PMID- 28697453
TI - Electricity production and microbial characterization of thermophilic microbial
fuel cells.
AB - Thermophilic microbial fuel cell (TMFC) offers many benefits, but the
investigations on the diversity of exoelectrogenic bacteria are scarce. In this
study, a two-chamber TMFC was constructed using ethanol as an electron donor, and
the microbial dynamics were analyzed by high-throughput sequencing and 16S rRNA
clone-library sequencing. The open-circuit potential of TMFC was approximately
650mV, while the maximum voltage was around 550mV. The maximum power density was
437mW/m2, and the columbic efficiency in this work was 20.5+/-6.0%. The
Firmicutes bacteria, related to the uncultured bacterium clone A55_D21_H_B_C01
with a similarity of 99%, accounted for 90.9% of all bacteria in the TMFC
biofilm. This unknown bacterium has the potential to become a new thermophilic
exoelectrogenic bacterium that is yet to be cultured. The development of TMFC
involved biotechnologies will be beneficial for the production of valuable
chemicals and generation of energy in the future.
PMID- 28697454
TI - Comparison of additives amendment for mitigation of greenhouse gases and ammonia
emission during sewage sludge co-composting based on correlation analysis.
AB - In this study, the pilot scale co-composting of sewage sludge (SS)+wheat straw
amended with 10% (dry weight ratio of basis) of three different additives
(zeolite, Ca-bentonite and medical stone) was conducted for 56days to evaluate
the greenhouse gases (GHGs) and nitrogen conservation efficacy and its
correlation with analyzed physicochemical, gaseous and biological parameters. The
results indicated that all of three additives could adequately buffer pH,
considerably increase temperature, and enhance organic matter degradation as well
as reduce ammonia and GHGs emission. Particularly, zeolite amended treatment
showed the maximum reduction of CH4 emission by 88.45% and less amount of
nitrogen loss by 28.80%, meanwhile reduced the maturity period by 2weeks. In
addition, the redundancy analysis was confirmed most significant relationship
between biological, GHGs, bacterial community and nutrients concentration in 10%
zeolite applied treatment than other treatments. The result suggested 10% zeolite
could be a suitable additive to improve the quality of sewage sludge composting.
PMID- 28697455
TI - Simultaneous enhancement of Chlorella vulgaris growth and lipid accumulation
through the synergy effect between light and nitrate in a planar waveguide flat
plate photobioreactor.
AB - Interval between adjacent planar waveguides and light intensity emitted from
waveguide surface were the primary two factors affecting light distribution
characteristics in the planar waveguide flat-plate photobioreactor (PW-PBR). In
this paper, the synergy effect between light and nitrate in the PW-PBR was
realized to simultaneously enhance microalgae growth and lipid accumulation.
Under an interval of 10mm between adjacent planar waveguides, 100% of microalgae
cells in regions between adjacent waveguides could be illuminated. Chlorella
vulgaris growth and lipid accumulation were synchronously elevated as light
intensities emitted from planar waveguide surface increasing. With an identical
initial nitrate concentration of 18mM, the maximum lipid content (41.66% in dry
biomass) and lipid yield (2200.25mgL-1) were attained under 560MUmolm-2s-1, which
were 86.82% and 133.56% higher relative to those obtained under 160MUmolm-2s-1,
respectively. The PW-PBR provides a promising way for microalgae lipid
production.
PMID- 28697456
TI - Hydrothermal carbonization of typical components of municipal solid waste for
deriving hydrochars and their combustion behavior.
AB - In this work, five typical components were employed as representative pseudo
components to indirectly complete previous established simulation system during
hydrothermal carbonization (HTC) of municipal solid waste. The fuel
characteristics and combustion behavior of HTC-derived hydrochars were evaluated.
Results clearly illustrated that the energy ranks of hydrochars were upgraded
after HTC. For paper and wood, superior combustion performances of their
hydrochars could achieve under suitable conditions. While for food, none positive
enrichments on combustion loss rate were observed for hydrochars due to its high
solubilization and decomposition under hot compressed water. It was noteworthy
that a new weight loss peak was detected for paper and food, suggesting that new
compounds were formed. For rubber, the HTC process made the properties of styrene
butadiene rubber more close to natural rubber. Therefore, the first peak of
hydrochars became significantly intense. While for plastic, only physical changes
of polypropylene and polyethylene were observed.
PMID- 28697457
TI - Bio-immobilization of dark fermentative bacteria for enhancing continuous
hydrogen production from cornstalk hydrolysate.
AB - Mycelia pellets were employed as biological carrier in a continuous stirred tank
reactor to reduce biomass washout and enhance hydrogen production from cornstalk
hydrolysate. Hydraulic retention time (HRT) and influent substrate concentration
played critical roles on hydrogen production of the bioreactor. The maximum
hydrogen production rate of 14.2mmol H2L-1h-1 was obtained at optimized HRT of 6h
and influent concentration of 20g/L, 2.6 times higher than the counterpart
without mycelia pellets. With excellent immobilization ability, biomass
accumulated in the reactor and reached 1.6g/L under the optimum conditions. Upon
further energy conversion analysis, continuous hydrogen production with mycelia
pellets gave the maximum energy conversion efficiency of 17.8%. These results
indicate mycelia pellet is an ideal biological carrier to improve biomass
retention capacity of the reactor and enhance hydrogen recovery efficiency from
lignocellulosic biomass, and meanwhile provides a new direction for economic and
efficient hydrogen production process.
PMID- 28697458
TI - Uptake and toxicity of CuO nanoparticles to Daphnia magna varies between indirect
dietary and direct waterborne exposures.
AB - Research examining the direct and indirect ecological effects of nanomaterials in
aquatic ecosystems is important for developing a more realistic understanding of
the environmental implications of nanotechnology. Copper oxide nanoparticles (CuO
NPs) are being used extensively in many industries but are considered highly
toxic to aquatic species residing in surface waters. Few studies have addressed
whether CuO NPs can be transferred through the aquatic food chain, and if such
indirect exposure to nanomaterials impacts their toxicity. We investigated the
uptake and trophic transfer of CuO NPs from the algae Chlorella vulgaris to the
crustacean Daphnia magna and assessed bio-partitioning and resulting toxicity. We
hypothesized that CuO NPs can be associated with algal cells and be transported
to predators through feeding, and that the chronic toxicity can be altered in
comparison to direct CuO NP exposure. For the indirect feeding exposure, algae
pre-incubated with CuO NPs (Cu-algae) were washed to remove loose NPs and fed to
D. magna while Cu uptake and toxicity were evaluated. For the direct waterborne
exposures, a parallel group of D. magna were exposed to equivalent concentrations
of CuO NPs while being fed unexposed algae. Using hyperspectral imaging we
observed strong surface associations between pre-incubated CuO NPs and algae used
in the feeding exposure, and quantified the average Cu content (0.15mg Cu/L) with
ICP-OES. Cu accumulated in daphnid bodies to a greater extent in direct
exposures, whereas molted carapaces and neonate offspring had more copper
following the indirect feeding exposure, implying that D. magna may regulate
internal Cu differently depending on the method of CuO NP delivery. Significantly
higher D. magna mortality was observed following direct exposure relative to
feeding exposure, and neonate production from adult daphnids exposed indirectly
to CuO NPs was significantly reduced. Thus, nanoparticle interaction with biota
at one trophic level may alter the biological response at the next trophic level
in a way that is dependent on the delivery scenario. This study highlights the
importance of evaluating potential ecological impacts of nanomaterials in more
relevant, complex exposure scenarios.
PMID- 28697459
TI - Responses of Landoltia punctata to cobalt and nickel: Removal, growth,
photosynthesis, antioxidant system and starch metabolism.
AB - Landoltia punctata has been considered as a potential bioenergy crop due to its
high biomass and starch yields in different cultivations. Cobalt and nickel are
known to induce starch accumulation in duckweed. We monitored the growth rate,
net photosynthesis rate, total chlorophyll content, Rubisco activity, Co2+ and
Ni2+ contents, activity of antioxidant enzymes, starch content and activity of
related enzymes under various concentrations of cobalt and nickel. The results
indicate that Co2+ and Ni2+ (<=0.5mgL-1) can facilitate growth in the beginning.
Although the growth rate, net photosynthesis rate, chlorophyll content and
Rubisco activity were significantly inhibited at higher concentrations (5mgL-1),
the starch content increased sharply up to 53.3% dry weight (DW) in L. punctata.
These results were attributed to the increase in adenosine diphosphate-glucose
pyrophosphorylase (AGPase) and soluble starch synthase (SSS) activities and the
decrease in alpha-amylase activity upon exposure to excess Co2+ and Ni2+. In
addition, a substantial increase in the antioxidant enzyme activities and high
flavonoid contents in L. punctata may have largely resulted in the metal
tolerance. Furthermore, the high Co2+ and Ni2+ contents (2012.9+/-18.8 and
1997.7+/-29.2mgkg-1 DW) in the tissue indicate that L. punctata is a
hyperaccumulator. Thus, L. punctata can be considered as a potential candidate
for the simultaneous bioremediation of Co2+- and Ni2+-polluted water and high
quality biomass production.
PMID- 28697460
TI - Effect of progesterone and its synthetic analogs on reproduction and embryonic
development of a freshwater invertebrate model.
AB - The presence of a mixture of progestogens at ng/L concentration levels in surface
waters is a worldwide problem. Only a few studies explore the effect of
progestogen treatment in a mixture as opposed to individual chemicals to shed
light on how non-target species respond to these contaminants. In the present
study, we used an invertebrate model species, Lymnaea stagnalis, exposed to a
mixture of four progestogens (progesterone, levonorgestrel, drospirenone, and
gestodene) in 10ng/L concentration for 3 weeks. Data at both physiological and
cellular/molecular level were analyzed using the ELISA technique,
stereomicroscopy combined with time lapse software, and capillary microsampling
combined with mass spectrometry. The treatment of adult Lymnaeas caused reduced
egg production, and low quality egg mass on the first week, compared to the
control. Starting from the second week, the egg production, and the quality of
egg mass were similar in both groups. At the end of the third week, the egg
production and the vitellogenin-like protein content of the hepatopancreas were
significantly elevated in the treated group. At the cellular level, accelerated
cell proliferation was observed during early embryogenesis in the treated group.
The investigation of metabolomic changes resulted significantly elevated hexose
utilization in the single-cell zygote cytoplasm, and elevated adenylate energy
charge in the egg albumen. These changes suggested that treated snails provided
more hexose in the eggs in order to improve offspring viability. Our study
contributes to the knowledge of physiological effect of equi-concentration
progestogen mixture at environmentally relevant dose on non-target aquatic
species.
PMID- 28697461
TI - Direct induction of functional neuronal cells from fibroblast-like cells derived
from adult human retina.
AB - Obtaining and manipulating neuronal cells are critical for neural biology basic
mechanism studies and translational applications. Recent advances in protocol
development and mechanism dissections have made direct induction of neuronal
cells from other somatic cells (iN) a promising strategy for such purposes. In
this study, we established a protocol to expand a population of fibroblast-like
cells from adult human retinal tissues, which can be reprogrammed into iNs by
forced expression of neurogenic transcription factors. Interestingly, the
combination of Ascl1, Brn2, Myt1l, and NeuroD1 transcription factors, which has
been demonstrated to be sufficient to reprogram human embryonic and dermal
fibroblasts into iNs, failed to reprogram the fibroblast-like cells from human
retinas into iNs. Instead, supplementing Ascl1 with Pax6 sufficed to convert the
cells into iNs, which exhibited a typical neuronal morphology, expressed neural
marker genes, displayed active and passive neuronal membrane activities, and made
synaptic communications with other neurons. Moreover, iNs converted from retina
derived fibroblast-like cells contained high ratios of gamma-Aminobutyric acid-
(GABA-) and tyrosine hydroxylase- (TH-) positive neurons. Thus, the present study
proposes a protocol that makes use of discarded retinal tissues from eye banks
for iN generation, and suggests that different sources of somatic cells require
different iN induction recipes and may also affect the iN subtype outputs. Our
study may also facilitate the future development of methods to convert resident
cells in situ into retinal neurons for treating retinal degeneration disease
purpose.
PMID- 28697462
TI - Acute dystonia associated with aripiprazole overdose in an adolescent boy.
PMID- 28697463
TI - Mental health, suicidality and hopelessness among university students in Turkey.
AB - Psychological symptoms of university students can affect perceptions of physical
and mental health and can influence the emergence of suicidal behavior. We
investigated the association among psychological symptoms, suicidal thoughts,
perceptions of physical and mental health in university students. 4330 students
at Onsekiz Mart University completed an internet-based questionnaire. 15.1% of
the students reported suicidal thoughts at least once in their lifetime. The
severity of mental symptoms was found to increase with a decrease in perceived
physical and mental health. 28.2% of the students had depression, 33.1% had
anxiety. This research aims to contribute to the extensive body of work done
regarding the mental health, suicidal thoughts and hopelessness among university
students.
PMID- 28697464
TI - Laminin-111 enriched fibrin hydrogels for skeletal muscle regeneration.
AB - Laminin (LM)-111 supplementation has improved muscle regeneration in several
models of disease and injury. This study investigated a novel hydrogel composed
of fibrinogen and LM-111. Increasing LM-111 concentration (50-450 MUg/mL) in
fibrin hydrogels resulted in highly fibrous scaffolds with progressively thinner
interlaced fibers. Rheological testing showed that all hydrogels had viscoelastic
behavior and the Young's modulus ranged from 2-6KPa. C2C12 myobalsts showed a
significant increase in VEGF production and decrease in IL-6 production on LM-111
enriched fibrin hydrogels as compared to pure fibrin hydrogels on day 4. Western
blotting results showed a significant increase in MyoD and desmin protein
quantity but a significant decrease in myogenin protein quantity in myoblasts
cultured on the LM-111 (450 MUg/mL) enriched fibrin hydrogel. Combined
application of electromechanical stimulation significantly enhanced the
production of VEGF and IGF-1 from myoblast seeded fibrin-LM-111 hydrogels. Taken
together, these observations offer an important first step toward optimizing a
tissue engineered constructs for skeletal muscle regeneration.
PMID- 28697465
TI - Combined photodynamic and antibiotic therapy for skin disorder via lipase
sensitive liposomes with enhanced antimicrobial performance.
AB - A lipase-sensitive singlet oxygen-producible and erythromycin-loaded liposome
(LSSPL) was developed for combination antibacterial therapy for skin disorder.
The LSSPL was synthesized by coating pullulan-pheophorbide a (PU-Pheo A)
conjugates onto erythromycin-loaded liposomes composed of 1,2-dipalmitoyl-sn
phosphatidylcholine (DPPC) and cholesterol. Lipase activity was chosen as the
environmental-stimulus for the controlled release of erythromycin and Pheo A from
LSSPL because skin inflammation-inducing Propionibacterium acnes (P. acnes)
secrete extracellular lipases. The presence of P. acnes lipases disrupted LSSPLs
by selective cleavage of their ester linkages, liberating erythromycin and Pheo
A. Along with the antibacterial effect of erythromycin, additional laser
irradiation onto Pheo A further achieved the inhibition of P. acnes growth and
treatment of P. acnes-infected inflammation in nude mice back skin. Therefore,
antimicrobial therapy, using a stimulus-responsiveness moiety, presents a
feasible way to treat bacteria-induced skin disorders.
PMID- 28697466
TI - A ratiometric two-photon probe for Ca2+ in live tissues and its application to
spinal cord injury model.
AB - Ratiometric imaging with a small-molecule probe is important for the in-situ
quantitative analysis of chemical events. We developed a ratiometric two-photon
fluorescent probe (SCa1-IREF) derived from dual dyes with different Stokes
shifts. This probe has two identical windows: a Ca2+-sensing window and an
internal reference window, with eliminated FRET interference. SCa1-IREF shows a
marked change in the ratio upon response with Ca2+, significant two-photon
brightness, considerable selectivity for Ca2+, and cell loading ability with low
cytotoxicity. The ratiometric two-photon microscopy images revealed that this
probe could directly and quantitatively estimate Ca2+ in live neurons and various
tissues including rat spinal cord tissue. The studies of spinal cord injury model
revealed that the Ca2+ level was significantly affected by elapsed time after
injury. These results will provide useful applications for in-situ [Ca2+]i
imaging and for the development of effective ratiometric probes.
PMID- 28697467
TI - Smoking prevalence and seizure control in Chinese males with epilepsy.
AB - Smoking has a negative effect on most diseases, yet it is under-investigated in
people with epilepsy; thus its role is not clear in the general population with
epilepsy. We performed a retrospective pilot study on males with epilepsy to
determine the smoking rate and its relationship with seizure control using
univariate analysis to calculate odds ratios (ORs) and also used a multi-variate
logistic regression model. The smoking rate in our sample of 278 individuals was
25.5%, which is lower than the general Chinese population smoking rate among
males of 52.1%. We used two classifications: the first classified epilepsy as
generalized, or by presumed topographic origin (temporal, frontal, parietal and
occipital). The second classified the dominant seizure type of an individual as
generalized tonic clonic seizure (GTCS), myoclonic seizure (MS), complex partial
seizure (CPS), simple partial seizure (SPS), and secondary GTCS (sGTCS). The
univariable analysis of satisfactory seizure control profile and smoking rate in
both classifications showed a trend towards a beneficial effect of smoking
although most were not statistically significant. Considering medication is an
important confounding factor that would largely influence seizure control, we
also conducted multi-variable analysis for both classifications with drug numbers
and dosage. The result of our model also suggested that smoking is a protective
factor. Our findings seem to suggest that smoking could have a potential role in
seizure control although confounders need exploration particularly in view of the
potential long term health effects. Replication in a much larger sample is needed
as well as case control studies to elucidate this issue.
PMID- 28697468
TI - Emission factors of unintentional HCB and PeCBz and their correlation with
PCDD/PCDF.
AB - Hexachlorobenzene (HCB) and pentachlorobenzene (PeCBz) have been listed as
unintentional POPs in the annex of the Stockholm Convention and thus, attracted
attention by government and researchers. Since the intentional production and use
has ceased in most countries, the unintentional releases to the environment have
increased. This study gathered 206 and 78 emission factors (EFs) of unintentional
HCB and PeCBz from scientific publications and governmental reports,
respectively. Most of the EFs referred to the release vector "air" (EFAir) and to
a less extent to "product" (EFProduct). EFs were proposed for different source
categories/classes used in the Toolkit according to the technologies that
released the HCB or PeCBz. Overall, lowest and highest EFAir for HCB were found
in the metallurgical industry range from 1 MUg/t in well controlled plants (coke,
iron and steel) up to 40,000 MUg/t (secondary zinc). EFs for PeCBz were in
similar order of magnitude. Due to lack of data, EFs to water, land or residue
cannot be proposed. Using linear regression and statistical analysis such as
Pearson correlation, we found strongest correlation of EFAir between HCB and
PeCBz (R2 = 0.79, P < 0.01) and weaker, but still significant, correlations for
EFAir between PCDD/PCDFTEQ and HCB (R2 = 0.56; P < 0.01) or PeCBz (R2 = 0.31 P <
0.01) for various thermal processes.
PMID- 28697469
TI - Differential expression of CURS gene during various growth stages, climatic
condition and soil nutrients in turmeric (Curcuma longa): Towards site specific
cultivation for high curcumin yield.
AB - Curcuma longa L., accumulates substantial amount of curcumin and essential oil.
Little is known about the differential expression of curcumin synthase (CURS)
gene and consequent curcumin content variations at different agroclimatic zones.
The present study aimed to evaluate the effect of climate, soil and harvesting
phase on expression of CURS gene for curcumin yield in two high yielding turmeric
cultivars. Expression of CURS gene at different experimental zones as well as at
different harvesting phase was studied through transcriptional analysis by qRT
PCR. Curcumin varied from 1.5 to 5% and 1.4-5% in Surama and Roma respectively.
The expression of CURS also varied from 0.402 to 5.584 fold in Surama and 0.856
5.217 fold in Roma. Difference in curcumin content at a particular zone varied
among different harvesting period from 3.95 to 4.31% in Surama and 3.57-3.83% in
Roma. Expression of CURS gene was also effected by harvesting time of the rhizome
which varied from 7.389 to 16.882 fold in Surama and 4.41-8.342 fold in Roma. The
CURS gene expression was found regardless of variations in curcumin content at
different experimental zones. This may be due to the effects of soil and
environmental variables. Expression was positively correlated with curcumin
content with different harvesting time at a particular zone. This find indicates
effect of soil and environment on molecular and biochemical dynamics of curcumin
biosynthesis and could be useful in genetic improvement of turmeric.
PMID- 28697470
TI - Structural diversity of alkali-soluble polysaccharides from the fruit cell walls
of tucuma (Astrocaryum aculeatum), a commelinid monocotyledon from the family
Arecaceae.
AB - The polysaccharide compositions of primary and secondary cell walls of members of
the family Arecaceae in the commelinid clade of monocotyledonous plants have
previously been found to be distinguishable from other commelinid families, and
to be more similar to those of non-commelinids. However, few studies have been
conducted. We aimed to extract and characterize the main cell-wall
polysaccharides in the fruit pulp of tucuma (Astrocaryum aculeatum), a member of
Arecaceae family. Hemicellulosic polysaccharides extracted by alkali from the
fruit pulp were present in greater proportions (6.4% yield) than water-extracted
ones (3.0% yield). Thus, the former was analyzed using monosaccharide
composition, methylation, molecular weight determination and 13C-NMR data. The
tucuma alkaline extract presented a highly ramified acidic galactoarabinoxylan
(53.7%), a linear (1 -> 5)-linked alpha-L-arabinan (27.8%), a low branched
glucuronoxylan (14.1%) and small portions of a xyloglucan (4.4%). The major
polysaccharide found in A. aculeatum (acidic galactoarabinoxylan) is similar to
those found in other commelinid plants such as grasses and cereals.
PMID- 28697471
TI - The relationship between airborne fine particle matter and emergency ambulance
dispatches in a southwestern city in Chengdu, China.
AB - High levels of fine particulate matter (PM2.5) are known to cause adverse effects
to human health. The goal of this study was to estimate the acute health effects
of short-term exposure to ambient PM2.5 by analyzing cause-specific emergency
ambulance dispatches as the endpoint in Chengdu, a city in Sichuan Province in
southwest China. The ambient PM2.5 concentration of Chengdu reached 63 MUg/m3 in
2015. Data related to the causes of specific emergency ambulance dispatches, air
pollution, and meteorological conditions were collected from 2013 to 2015 (1095
days). A generalized additive model (GAM) was constructed to control the
confounding conditions and to estimate the effects of PM2.5 on human health
conditions. Emergency ambulance dispatches for all causes with (RR for lag0 =
1.0010, 95%CI: 1.0002, 1.0019) or without injuries (RR for lag0 = 1.0012, 95%CI:
1.0002, 1.0022), respiratory diseases (RR for lag0 = 1.0051, 95%CI: 1.0012,
1.0089), and cardiovascular diseases (RR for lag0 = 1.0041, 95%CI: 1.0009,
1.0074) were associated with ambient PM2.5 concentrations in Chengdu. In
addition, the effects of PM2.5 were not confounded by ozone.
PMID- 28697472
TI - Protective effects of grape stem extract against UVB-induced damage in C57BL mice
skin.
AB - Humans have become exposed to another form of a trait which is ultraviolet B
(UVB) radiation reaching the earth's surface. This has become a major source of
oxidative stress that ultimately leads to inflammation, DNA damage, photoaging
and pigmentation disorders etc. Although several studies have shown the photo
protective role of different grape parts like the fruits and seeds, little or no
data demonstrating the in vivo photo-protective role of grape stem, which is the
most discarded part of the grape are available. We evaluated the protective
influence of grape stem extract against UVB-induced oxidative damage in C57BL
mice characterized by epidermal hyperplasia, pigmentation, collagen degradation
and inflammation. Grape stem extract was administered topically 1week before UVB
irradiation (120mJ/cm2) and continued until the termination of the experiment. A
group of non-irradiated mice and a group of irradiated mice topically
administered with propylene were used as a negative and positive control.
Epidermal thickness, pigmentation, erythema, mast cell and neutrophil
infiltration, collagen degradation and COX-2, Nrf2, and HO-1 expressions were
evaluated. Grape stem extract markedly recovered skin damage induced by the UVB
radiation through the prevention of epidermal hyperplasia, pigmentation,
erythema, mast cell and neutrophil infiltrations, collagen degradation and COX-2,
Nrf2, and HO-1 expressions. Our study demonstrated for the first time in C57BL
mice that grape stem extract reduces UVB-induced oxidative damage and hence can
play a protective role in skin photo-damage.
PMID- 28697473
TI - Biophysical studies on the interaction of a novel oxime based palladium(II)
complex with DNA and RNA.
AB - A novel oxime based palladium(II) complex (1) has been synthesized out of the
reaction of a Schiff base ligand, 1-phenyl-1-(pyridin-2-yl-hydrazono)-propan-2
one oxime (LH2) with Na2[PdCl4] in THF. Red and diamagnetic 1 has thoroughly been
characterized by several analytical and spectroscopic means like CHN, ESI-MS, FAB
MS, FT-IR, 1H NMR, 13C NMR, UV-Vis and molar electrical conductivity
measurements. Geometry optimizations at the level of DFT reveals that the Pd(II)
centre in 1 is nested in a square-planar 'N3Cl' coordination environment. Semi
empirical BVS mode of analysis was also undertaken to reproduce the oxidation
state of the palladium centre. 1 shows quasi-reversible Pd(II)/Pd(III) and
Pd(III)/Pd(IV) redox couples in its CV in acetonitrile. The photophysical studies
reveal that 1 is two-fold less emissive than its tethering ligand. Several
biophysical studies have been undertaken to demonstrate the binding aspects of
DNA and RNA with 1. Ethidium bromide displacement study concludes that 1 is
partially intercalated to the CT DNA. Thermodynamic parameters of binding have
also been determined from temperature dependent fluorescence spectroscopy
employing the van't Hoff plot. The binding constants as determined from McGhee
von Hippel equation (Scatchard plot) indicate that 1 is a good binder of both DNA
and RNA. However, the magnitude of the binding constant as determined for RNA
interaction with 1 is found to be higher than that for DNA interaction.
PMID- 28697474
TI - Extraction of natural colorant from purple sweet potato and dyeing of fabrics
with silver nanoparticles for augmented antibacterial activity against skin
pathogens.
AB - The main objective of this study was to extract natural colorant from purple
sweet potato powder (PSPP) via a water bath and ultrasound water bath using
acidified ethanol (A. EtOH) as the extraction solvent. When optimizing the
colorant extraction conditions of the solvents, acidified ethanol with ultrasound
yielded a high extraction capacity and color intensity at pH2, temperature of 80
degrees C, 20mL of A. EtOH, 1.5g of PSPP, time of 45min, and ultrasonic output
power of 75W. Subsequently, the colorant was extracted using the optimized
conditions for dyeing of textiles (leather, silk, and cotton). This natural
colorant extraction technique can avoid serious environmental pollution during
the extraction and is an alternative to synthetic dyes, using less solvent and
simplified abstraction procedures. The extracted purple sweet potato natural
colorant (PSPC) was used to dye leather, silk, and cotton fabrics in an eco
friendly approach with augmented antibacterial activity by in situ synthesis of
silver nanoparticles (AgNPs) and dyeing. The optimal dyeing conditions for higher
color strength (K/S) values were pH2 and 70 degrees C for 45min. The colorimetric
parameters L*, a*, b*, C, and H were measured to determine the depth of the
color. The Fourier transform infrared spectroscopy (FTIR) spectra of undyed
control, dyed with PSPC and dyed with blend of PSPC and AgNPs treated leather,
silk and cotton fabric were investigated to study the interaction among fiber
type, nanoparticles, and dye. The structural morphology of leather and silk and
cotton fabrics and the anchoring of AgNPs with elemental compositions were
investigated by scanning electron microscopy-energy-dispersive X-ray spectroscopy
(SEM-EDS). The dry and wet rubbing fastness for dye alone and dye with
nanoparticles were grade 4-5 and 4, respectively. Thus, the results of the
present study clearly suggest that in situ synthesis of AgNPs along with dyeing
should be considered in the development of antimicrobial textile finishes.
PMID- 28697475
TI - Light response of sunflower and canola as affected by plant density, plant
genotype and N fertilization.
AB - Crop response to light is an important parameter determining crop growth. Three
field (split plots) experiments were conducted to investigate the effects of
plant density, plant genotype and N fertilization on the light absorption and
light extinction of sunflower (Helianthus annuus L.) and canola (Brassica napus
L.). A detailed set of plant growth, light absorption and crop yield and oil
related parameters were determined. Light was measured at noon during the sunny
days with clear sky. In experiment I, although the plant density (PD) of 14
resulted in the highest rate of sunflower light absorption (31.37%) and light
extinction (0.756), the highest rate of grain yield and grain oil yield was
resulted at PD12 at 3639 and 1457.9kg/ha, respectively; as well as by genotype
SUP.A. In experiment II (canola), PD80 resulted in the highest rate of light
absorption (13.13%), light extinction (0.63), grain yield (2189.4kg/ha) and grain
oil yield (556.54kg/ha). This was also the case for Genotype H. In experiment III
(canola), although N150 resulted in the highest rate of light absorption (10.74%)
and light extinction (0.48), the highest rate of grain yield (3413.6kg/ha) and
grain oil yield (891.86kg/ha) was resulted at N100 as well as by Genotype H401.
Results indicate how light properties, crop growth and yield of sunflower and
canola can be affected by plant and environmental parameters, which are also of
practical use by farmers.
PMID- 28697476
TI - Characterizing the binding interaction of fungicide boscalid with bovine serum
albumin (BSA): A spectroscopic study in combination with molecular docking
approach.
AB - Boscalid, a carboxamide fungicide, is used in the treatment of grey mould and
powdery mildew, widely applied to a variety of crops and fruits such as rice,
wheat, grapes and pears. It will become a potential risk for health due to its
widely application and residue in crops and fruits. In this study, the binding
interaction between boscalid and bovine serum albumin (BSA) was characterized
using steady-state fluorescence spectroscopy, ultraviolet spectroscopy (UV),
synchronous fluorescence spectroscopy, 3D fluorescence spectroscopy, Fourier
transform infrared spectroscopy (FT-IR) and molecular docking to ascertain the
store, transport and distribution of boscalid in vivo. The experimental results
indicated that the fluorescence of BSA was quenched due to the forming the static
boscalid-BSA complex with the binding constant of 4.57*103M-1 at 298 K and
boscalid bound on the subdomain III A (site II) of BSA through van der Waals
force and hydrogen bonding interaction. The binding process of boscalid with BSA
was spontaneous and enthalpy-driven process based on DeltaG0<0 and
|DeltaH0|>T|DeltaS0| over the studied temperature range. Meanwhile, the obvious
change in the conformation of boscalid was observed while the slight change in
the conformation of BSA when binding boscalid to the BSA, implying that the
flexibility of boscalid contributes to increasing the stability of the boscalid
BSA complex.
PMID- 28697477
TI - Green synthesis of gold nanoparticles using a cheap Sphaeranthus indicus extract:
Impact on plant cells and the aquatic crustacean Artemia nauplii.
AB - The impact of green-fabricated gold nanoparticles on plant cells and non-target
aquatic species is scarcely studied. In this research, we reported an environment
friendly technique for the synthesis of gold nanoparticles (Au NPs) using the
Sphaeranthus indicus leaf extract. The formation of the metal NPs was
characterized by UV-Visible and FT-IR spectroscopy, XRD, SEM and TEM analyses.
The UV-Visible spectra of Au NPs showed a surface plasmon resonance peak at
531nm. FT-IR analysis indicated functional bio-molecules associated with Au NPs
formation. The crystalline nature of Au nanoparticles was confirmed by their XRD
diffraction pattern. TEM revealed the spherical shape with a mean particle size
of 25nm. Au NPs was tested at 0, 1, 3, 5, 7 and 10% doses in mitotic cell
division assays, pollen germination experiments, and in vivo toxicity trials
against the aquatic crustacean Artemia nauplii. Au NPs did not show any toxic
effects on plant cells and aquatic invertebrates. Notably, Au NPs promoted
mitotic cell division in Allium cepa root tip cells and germination of Gloriosa
superba pollen grains. Au NPs showed no mortality on A. nauplii, all the tested
animals showed 100% survivability. Therefore, these Au NPs have potential
applications in the development of pollen germination media and plant tissue
culture.
PMID- 28697478
TI - Shedding lights on the flexible-armed porphyrins: Human telomeric G4 DNA
interaction and cell photocytotoxicity research.
AB - DNA polymorphism exerts a fascination on a large scientific community. Without
crystallographic structural data, clarification of the binding modes between G
quadruplex (G4) and ligand (complex) is a challenging job. In the present work,
three porphyrin compounds with different flexible carbon chains (arms) were
designed, synthesized and characterized. Their binding, folding and stabilizing
abilities to human telomeric G4 DNA structures were comparatively researched.
Positive charges at the end of the flexible carbon chains seem to be favorable
for the DNA-porphyrin interactions, which were evidenced by the spectral results
and further confirmed by the molecular docking calculations. Biological function
analysis demonstrated that these porphyrins show no substantial inhibition to
Hela, A549 and BEL 7402 cancer cell lines under dark while exhibit broad
inhibition under visible light. This significantly enhanced photocytotoxicity
relative to the dark control is an essential property of photochemotherapeutic
agents. The feature of the flexible arms emerges as critical influencing factors
in the cell photocytotoxicity. Moreover, an ROS-mediated mitochondrial
dysfunction pathway was suggested for the cell apoptosis induced by these
flexible-armed porphyrins. It is found that the porphyrins with positive charges
located at the end of the flexible arms represent an exciting opportunity for
photochemotherapeutic anti-cancer drug design.
PMID- 28697479
TI - False memories, but not false beliefs, affect implicit attitudes for food
preferences.
AB - Previous studies have found that false memories and false beliefs of childhood
experiences can have attitudinal consequences. Previous studies have, however,
focused exclusively on explicit attitude measures without exploring whether
implicit attitudes are similarly affected. Using a false feedback/imagination
inflation paradigm, false memories and beliefs of enjoying a certain food as a
child were elicited in participants, and their effects were assessed using both
explicit attitude measures (self-report questionnaires) and implicit measures (a
Single-Target Implicit Association Test). Positive changes in explicit attitudes
were observed both in participants with false memories and participants with
false beliefs. In contrast, only participants with false memories exhibited more
positive implicit attitudes. The findings are discussed in terms of theories of
explicit and implicit attitudes.
PMID- 28697480
TI - Social perception and aging: The relationship between aging and the perception of
subtle changes in facial happiness and identity.
AB - Previous findings suggest that older adults show impairments in the social
perception of faces, including the perception of emotion and facial identity. The
majority of this work has tended to examine performance on tasks involving young
adult faces and prototypical emotions. While useful, this can influence
performance differences between groups due to perceptual biases and limitations
on task performance. Here we sought to examine how typical aging is associated
with the perception of subtle changes in facial happiness and facial identity in
older adult faces. We developed novel tasks that permitted the ability to assess
facial happiness, facial identity, and non-social perception (object perception)
across similar task parameters. We observe that aging is linked with declines in
the ability to make fine-grained judgements in the perception of facial happiness
and facial identity (from older adult faces), but not for non-social (object)
perception. This pattern of results is discussed in relation to mechanisms that
may contribute to declines in facial perceptual processing in older adulthood.
PMID- 28697481
TI - Childhood exposure to Libby amphibole asbestos and respiratory health in young
adults.
AB - OBJECTIVES: Vermiculite ore containing Libby amphibole asbestos (LAA) was mined
in Libby, MT, from the 1920s-1990. Recreational and residential areas in Libby
were contaminated with LAA. This objective of this study was to characterize
childhood exposure to LAA and investigate its association with respiratory health
during young adulthood. METHODS: Young adults who resided in Libby prior to age
18 completed a health and activity questionnaire, pulmonary function testing,
chest x-ray and HRCT scan. LAA exposure was estimated based on participant report
of engaging in activities with potential LAA exposure. Quantitative LAA estimates
for activities were derived from sampling data and literature reports. RESULTS: A
total of 312 participants (mean age 25.1 years) were enrolled and reported
respiratory symptoms in the past 12 months including pleuritic chest pain (23%),
regular cough (17%), shortness of breath (18%), and wheezing or whistling in the
chest (18%). Cumulative LAA exposure was significantly associated with shortness
of breath (aOR = 1.12, 95% CI 1.01-1.25 per doubling of exposure). Engaging in
recreational activities near Rainy Creek Road (near the former mine site) and the
number of instances heating vermiculite ore to make it expand or pop were also
significantly associated with respiratory symptoms. LAA exposure was not
associated with pulmonary function or pleural or interstitial changes on either
chest x-ray or HRCT. CONCLUSIONS: Pleural or interstitial changes on x-ray or
HRCT were not observed among this cohort of young adults. However, childhood
exposure to LAA was significantly associated with respiratory symptoms during
young adulthood. Pleuritic chest pain, in particular, has been identified as an
early symptom associated with LAA exposure and therefore warrants continued
follow-up given findings of progressive disease in other LAA exposed populations.
PMID- 28697482
TI - A new approach for evaluating transformations of dissolved organic matter (DOM)
via high-resolution mass spectrometry and relating it to bacterial activity.
AB - Streams are important sites of transformation of dissolved organic matter (DOM).
The molecular characterization of DOM-quality changes requires sophisticated
analytical evaluation techniques. The goal of our study was to link molecular DOM
transformation with bacterial activity. We measured the degradation of leaf
leachate over a gradient of bacterial production obtained by different rates of
percolation of sediments in seven experimental flumes on five sampling dates. We
developed a new strategy for evaluating molecular formula data sets obtained by
ultra-high resolution Fourier transform ion cyclotron resonance mass spectrometry
(FTICR MS), in which the time-dependent change of component abundance was fitted
by a linear regression model after normalization of mass peak intensities. All
components were categorized by calculating the slope (change of percent intensity
per day) in each of the seven flumes. These slopes were then related to
cumulative bacterial production. The concentration of DOM decreased quickly in
all flumes. Bacterial activity was higher in flumes with percolated sediment than
in those without percolation, whereas plankton bacterial activity was higher in
flumes without percolation or without sediment. There were no differences in
molecular-DOM characteristics between flumes, but there were distinct changes
over time. Positive slopes, i.e. increasing intensities over time, were found for
small molecules (MW < 450 Da) and high O/C ratios, whereas decreasing intensities
were observed less often and only for large molecules and low O/C ratios. The
positive slopes of produced components showed a positive relationship to
bacterial production for small and for oxygen-rich components. The negative
slopes of degraded components were negatively related to bacterial production for
large and for oxygen-deficient molecules. Overall, the approach provided new
insights into the transformation of specific molecular DOM components.
PMID- 28697483
TI - Under-oil superhydrophilic wetted PVDF electrospun modified membrane for
continuous gravitational oil/water separation with outstanding flux.
AB - Water in the world is becoming an increasingly scarce commodity and the membrane
technology is a most effective strategy to address this issue. However, the
fouling and low flux of the polymeric membrane remains the big challenges. Novel
modified Polyvinylidene fluoride (PVDF) membrane was introduced, in this work,
using a novel treatment technique for an electrospun polymeric PVDF membrane to
be used in oil/water separation systems. The Characterizations of the modified
and pristine membranes showed distinct changes in the phase and crystal structure
of the membrane material as well as the wettability. The modification process
altered the surface morphology and structure of the membrane by forming
hydrophilic microspheres on the membrane surface. Therefore, the proposed
treatment converts the membrane from highly hydrophobic to be a superhydrophilic
under-oil when wetted with water. Accordingly, in the separation of oil/water
mixtures, the modified membrane can achieve an outstanding flux of 20664 L/m2. hr
under gravity, which is higher than the pristine membrane by infinite times.
Moreover, in the separation of the emulsion, a high flux of 2727 L/m2. h was
achieved. The results exhibited that the modified membrane can treat a huge
amount of oily water with a minimal energy consumption. The corresponding
separation efficiencies of both of oil/water mixtures and emulsion are more than
99%. The achieved characteristics for the modified and pristine membranes could
be exploited to design a novel continuous system for oil/water separation with an
excellent efficiency.
PMID- 28697484
TI - Organic compounds in hydraulic fracturing fluids and wastewaters: A review.
AB - High volume hydraulic fracturing (HVHF) of shale to stimulate the release of
natural gas produces a large quantity of wastewater in the form of flowback
fluids and produced water. These wastewaters are highly variable in their
composition and contain a mixture of fracturing fluid additives, geogenic
inorganic and organic substances, and transformation products. The qualitative
and quantitative analyses of organic compounds identified in HVHF fluids,
flowback fluids, and produced waters are reviewed here to communicate knowledge
gaps that exist in the composition of HVHF wastewaters. In general, analyses of
organic compounds have focused on those amenable to gas chromatography, focusing
on volatile and semi-volatile oil and gas compounds. Studies of more polar and
non-volatile organic compounds have been limited by a lack of knowledge of what
compounds may be present as well as quantitative methods and standards available
for analyzing these complex mixtures. Liquid chromatography paired with high
resolution mass spectrometry has been used to investigate a number of additives
and will be a key tool to further research on transformation products that are
increasingly solubilized through physical, chemical, and biological processes in
situ and during environmental contamination events. Diverse treatments have been
tested and applied to HVHF wastewaters but limited information has been published
on the quantitative removal of individual organic compounds. This review focuses
on recently published information on organic compounds identified in flowback
fluids and produced waters from HVHF.
PMID- 28697485
TI - Proteins from the Rhinella schneideri parotoid gland secretion exhibit anti
nociceptive effect against nociception induced by inflammation.
AB - As proteins isolated from the Rhinella schneideri parotoid gland secretion (RsPP)
exhibit anti-inflammatory activity, the goal of this work was to investigate
their anti-nociceptive effects using acetic acid-induced writhing, formalin, and
hot-plate tests. The intraperitoneal administration of RsPP (2.5 or 5mg/kg) one
hour prior to stimuli significantly reduced the abdominal constrictions induced
by acetic acid (73.06 and 72.69% inhibition, respectively) and the inflammatory
phase of paw licking time induced by formalin (69.3% inhibition, at 2.5mg/kg).
However, RsPP (1, 2.5 or 5mg/kg) did not change the latency in response at the
hot-plate test. The involvement of inflammatory mediators on the anti-nociceptive
effect of RsPP was further demonstrated. RsPP (2.5mg/kg) significantly inhibited
the inflammatory peak of paw edema induced by histamine (44.0%), bradykinin
(51.3%), or prostaglandin E2 (53.7%). Our data indicate that RsPP may act on the
pain process by inhibiting the effect of inflammatory mediators.
PMID- 28697486
TI - Oxidant production and SOD1 protein expression in single skeletal myofibers from
Down syndrome mice.
AB - Down syndrome (DS) is a genetic condition caused by the triplication of
chromosome 21. Persons with DS exhibit pronounced muscle weakness, which also
occurs in the Ts65Dn mouse model of DS. Oxidative stress is thought to be an
underlying factor in the development of DS-related pathologies including muscle
dysfunction. High-levels of oxidative stress have been attributed to triplication
and elevated expression of superoxide dismutase 1 (SOD1); a gene located on
chromosome 21. The elevated expression of SOD1 is postulated to increase
production of hydrogen peroxide and cause oxidative injury and cell death.
However, it is unknown whether SOD1 protein expression is associated with greater
oxidant production in skeletal muscle from Ts65Dn mice. Thus, our objective was
to assess levels of SOD1 expression and oxidant production in skeletal myofibers
from the flexor digitorum brevis obtained from Ts65Dn and control mice.
Measurements of oxidant production were obtained from myofibers loaded with 2',7'
dichlorodihydrofluorescein diacetate (DCFH2-DA) in the basal state and following
15min of stimulated unloaded contraction. Ts65Dn myofibers exhibited a
significant decrease in basal DCF emissions (p < 0.05) that was associated with
an approximate 3-fold increase in SOD1 (p < 0.05). DCF emissions were not
affected by stimulating contraction of Ts65Dn or wild-type myofibers (p > 0.05).
Myofibers from Ts65Dn mice tended to be smaller and myonuclear domain was lower
(p < 0.05). In summary, myofibers from Ts65Dn mice exhibited decreased basal DCF
emissions that were coupled with elevated protein expression of SOD1. Stimulated
contraction in isolated myofibers did not affect DCF emissions in either group.
These findings suggest the skeletal muscle dysfunction in the adult Ts65Dn mouse
is not associated with skeletal muscle oxidative stress.
PMID- 28697487
TI - Predictors of illness anxiety symptoms in patients with obsessive compulsive
disorder.
AB - Illness anxiety and OCD symptoms appear to overlap in their presentation as well
as in other conceptually important ways (e.g., dysfunctional cognitions). Little
research, however, has directly examined these putative relationships. The
present study examined the extent to which illness anxiety symptoms were
associated with OCD symptom dimensions and relevant cognitive factors in a large
treatment-seeking sample of patients with OCD. Patients completed a battery of
self-report measures of OCD and health anxiety symptoms and related cognitive
biases. Results from regression analyses indicated that illness anxiety symptoms
were associated with harm obsessions and checking rituals, as well as with the
tendency to overestimate threat and responsibility for harm. Illness anxiety was
not associated with perfectionism. Conceptual and clinical implications of these
findings are discussed.
PMID- 28697488
TI - The interpersonal adverse effects reported by 1008 users of antidepressants; and
the incremental impact of polypharmacy.
AB - Antidepressant drugs are being prescribed at ever increasing rates
internationally, despite marginal benefit compared to placebo and a range of
adverse effects. Most studies of adverse effects focus on biological phenomena.
This article presents the results of an online survey of 1008 self-selected anti
depressant users in Britain, which asked about five adverse effects in the
interpersonal domain. The most commonly reported among participants who took only
antidepressants were: Sex Life - 43.7%, Work or Study - 27.0% and Social Life -
23.5%. These rates of interpersonal adverse effects were even higher for the 52%
of participants who were also taking one or more other psychiatric drugs. Only
about a half (48%) felt they had been given enough information about side effects
by the prescriber. Those initially prescribed medication by a psychiatrist were
more likely to be on several types of drugs and reported more adverse effects
than those whose prescriber was a General Practitioner (GP). Researchers and
prescribers are encouraged to pay greater attention to interpersonal adverse
effects.
PMID- 28697490
TI - The Influence of Blood Pressure on Fetal Aortic Distensibility: An Animal
Validation Study.
AB - BACKGROUND/AIMS: Aortic distension waveforms describe the change in diameter or
cross-sectional area over the cardiac cycle. We aimed to validate the association
of aortic fractional area change (AFAC) with blood pressure (BP) in a fetal lamb
model. METHODS: Four pregnant ewes underwent open fetal surgery under general
anesthesia at 107-120 gestational days. A 4-Fr catheter was introduced into the
fetal femoral artery and vein, or the carotid artery and jugular vein. The
thoracic aorta was imaged using real-time ultrasound; AFAC was calculated using
offline speckle tracking software. Measurements of invasive BP and AFAC were
obtained simultaneously and averaged over 10 cardiac cycles. BP was increased by
norepinephrine infusion and the association of aortic distensibility with BP was
assessed. RESULTS: Baseline measurements were obtained from 4 lambs, and changes
in aortic distensibility with increasing BP were recorded from 3 of them. A
positive correlation was found between AFAC and systolic BP (r = 0.692, p =
0.001), diastolic BP (r = 0.647, p = 0.004), mean BP (r = 0.692, p = 0.001), and
BP amplitude (r = 0.558, p = 0.016) controlled for heart rate. No association was
found between BP and maximum or minimum aortic area. CONCLUSION: AFAC provides a
quantifiable measure of aortic distensibility and correlates with systolic BP,
diastolic BP, mean BP, and BP amplitude in a fetal lamb model.
PMID- 28697489
TI - Subjective sleep disturbance in Chinese adults with epilepsy: Associations with
affective symptoms.
AB - BACKGROUND: As well as being a very common neurological disease worldwide,
epilepsy significantly impairs patients' emotional, behavioral, and cognitive
functioning. Sleep disturbances are the most frequent complaint in patients with
epilepsy. The present study assesses the impact of a range of affective symptoms
on subjective sleep quality and sleep disturbances in Chinese adults with
epilepsy. METHODS: Adults with epilepsy who visited our epilepsy clinic from July
2015 to March 2016 were enrolled in our study. Both patients and healthy controls
completed the Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale
(ESS), Insomnia Severity Index (ISI), Beck Depression Inventory-II (BDI-II), Beck
Anxiety Inventory (BAI), and Mini-mental State Examination (MMSE). Subjective
sleep quality and sleep disturbances were examined with regard to self-reported
symptoms of depression and anxiety, seizure-related factors, and demographic
factors. RESULTS: The PSQI scores and ISI scores of patients were significantly
higher (indicating lower quality sleep and more serious insomnia) than those of
the control group. Symptoms associated with depression and anxiety were
independently related to impaired subjective sleep quality and insomnia.
Affective symptoms explained more of the variance in PSQI scores and ISI scores
than did seizure-related or demographic variables. In addition, these variables
also seemed to be less powerful contributing factors to subjective sleep quality
and insomnia than affective symptoms, several seizure-related factors, such as
seizure control, partial seizures and duration of epilepsy, which are also
significantly associated with subjective sleep quality and insomnia. In addition,
use of lamotrigine (LTG) was also associated with insomnia and use of clonazepam
(CZP) and phenobarbital (PB) with daytime sleepiness in patients with epilepsy.
CONCLUSION: Chinese adults with epilepsy have poorer self-reported subjective
sleep quality and a higher prevalence of insomnia than the control group.
Depressive- and anxiety-related symptoms independently exert an adverse effect on
the subjective sleep quality and insomnia of patients. In addition, seizure
control, partial seizures, and the duration of epilepsy affect the quality of
sleep and insomnia in patients, but seem less powerful predictors of sleep
quality and insomnia than affective symptoms. Early identification and treatment
of affective symptoms is of great importance in improving the sleep quality and
insomnia of patients with epilepsy.
PMID- 28697491
TI - TRPC1, TRPC3, and TRPC4 in Rat Orofacial Structures.
AB - TRPC (transient receptor potential cation channel subfamily C) members are
nonselective monovalent cation channels and control Ca2+ inflow. In this study,
immunohistochemistry for TRPC1, TRPC3, and TRPC4 was performed on rat oral and
craniofacial structures to elucidate their distribution and function in the
peripheries. In the trigeminal ganglion (TG), 56.1, 84.1, and 68.3% of sensory
neurons were immunoreactive (IR) for TRPC1, TRPC3, and TRPC4, respectively. A
double immunofluorescence method revealed that small to medium-sized TG neurons
co-expressed TRPCs and calcitonin gene-related peptide. In the superior cervical
ganglion, all sympathetic neurons showed TRPC1 and TRPC3 immunoreactivity.
Parasympathetic neurons in the submandibular ganglion, tongue, and parotid gland
were TRPC1, TRPC3, and TRPC4 IR. Gustatory and olfactory cells were also IR for
TRPC1, TRPC3, and/or TRPC4. In the musculature, motor endplates expressed TRPC1
and TRPC4 immunoreactivity. It is likely that TRPCs are associated with sensory,
autonomic, and motor functions in oral and craniofacial structures.
PMID- 28697492
TI - Incidence and Causes for Early Ticagrelor Discontinuation: A "Real-World" Dutch
Registry Experience.
AB - OBJECTIVES: The PLATO trial revealed superiority of ticagrelor over clopidogrel
for the prevention of atherothrombotic events in patients with acute coronary
syndrome. However, adverse events such as bleeding, dyspnea, and bradycardia were
frequently reported, potentially leading to excess early ticagrelor
discontinuation (ETD), later confirmed in the PEGASUS trial. We here evaluated
the incidence and causes for ETD in a real-world patient cohort in a high-volume
nonacademic percutaneous coronary intervention center in the Netherlands.
METHODS: In a retrospective single-center registry, all patients discharged from
the hospital with a new ticagrelor prescription were screened for ETD. Follow-up
data were obtained using the hospital electronic patient file records and
confirmed by telephone contact with the patient and/or general practitioner, if
necessary, to complement the data. RESULTS: Ticagrelor was prescribed in 354
patients between December 2011 and December 2012. The follow-up data were
available in 301 patients with a mean follow-up duration of 330 days. ETD or
switching to another antiplatelet agent occurred in 73 patients (24.3%), mostly
due to dyspnea (11.6%), bleeding (3.7%), or planned major surgery (2.7%).
CONCLUSIONS: Almost one quarter of ticagrelor patients were discontinued
prematurely or switched to another antiplatelet agent within 1 year, mostly due
to dyspnea or bleeding.
PMID- 28697493
TI - Does the Margin Matter in Esophageal Cancer.
AB - BACKGROUND: The prognostic impact of circumferential resection margin (CRM)
involvement in resected esophageal cancer (EC) is controversial discussed. The
College of American Pathologists (CAP) and the Royal College of Pathologists
(RCP) provide 2 different definitions of CRM involvement. The aim of this
systematic review was to evaluate the clinical significance of CRM involvement on
patients' survival following esophagectomy due to EC. METHODS: PubMed, Science
Direct, and Google scholar were searched for studies analyzing the clinical
impact of CRM in EC. SUMMARY: A total of 28 studies analyzed the prognostic
effect of a positive CRM in EC. A wide range of CRM involvement (8.6-83.1%) was
reported. Both available meta-analyses found a significant association between a
positive CRM and patients' survival irrespective of RCP (OR 2.52 [95% CI 1.96
3.25; p < 0.001]) or CAP (OR 4.02 [95% CI 2.25-7.20; p < 0.001]) criteria. The
influence of neoadjuvant therapy on the CRM remains unclear. Key Messages: CRM
involvement is a useful parameter for EC patients' prognosis. The application of
CAP criteria should be preferred since patients with a poor prognosis can be
identified more sufficiently. Neoadjuvant therapy and en bloc transthoracic
esophagectomy show favorable results for achievement of negative CRM.
PMID- 28697494
TI - Diet and Activity of Macaca assamensis in Wild and Semi-Provisioned Groups in
Shivapuri Nagarjun National Park, Nepal.
AB - Studying the behavioural flexibility and adaptability of macaques to different
habitats is one approach to designing a conservation plan. To determine the
activity budget and feeding behaviour and evaluate the effects of seasonality in
wild and human- altered habitats of Assamese macaques (Macaca assamensis), we
conducted this study in the Nagarjun forest of Shivapuri-Nagarjun National Park
(SNNP) in central Nepal. We also updated the list of plant food items of Assamese
macaques in the SNNP. Using scan and all-occurrence sampling, we recorded the
diets and activities of Assamese macaques in 2 social groups, a wild-feeding
group (WG) and a semi-provisioned group (SPG), throughout the year from August
2013 to July 2014. Both groups spent most of their time in feeding activities and
were quite arboreal, but there were significant differences in the activity
budgets and diets between the groups. Human food was the main component of the
diet for the SPG, whereas it was fruit for the WG, indicating a normally
frugivorous diet. Furthermore, the activity budget and diet composition varied in
response to the season. These results indicate that provisioning alters the
activity and feeding behaviour of macaques, and can also increase human-macaque
conflict and disease transmission.
PMID- 28697495
TI - Electrolyte and Acid-Base Abnormalities in Infants with Community-Acquired Acute
Pyelonephritis: Prospective Cross-Sectional Study.
AB - BACKGROUND: Retrospective case series suggest that abnormalities in fluid,
electrolyte, and acid-base homeostasis may occur among infants with a febrile
urinary tract infection. Potentially inaccurate laboratory methods of sodium
testing have often been used. METHODS: Between January 2009 and June 2016, we
managed 80 previously healthy infants (52 males and 28 females) >=4 weeks to <=24
months of age with their first episode of acute pyelonephritis. Ionized sodium,
ionized potassium and ionized chloride were determined by direct potentiometry,
as recommended by the International Federation of Clinical Chemistry. Bicarbonate
was calculated from pH and carbon dioxide pressure. RESULTS: Electrolyte or acid
base abnormalities were disclosed in 59 (74%) of the 80 infants: hyponatremia (n
= 54), hypobicarbonatemia (n = 18), hyperkalemia (n = 14), hyperbicarbonatemia (n
= 6), hypochloremia (n = 3), hypokalemia (n = 3), and hyperchloremia (n = 1).
None of the patients was found to be hypernatremic. Patients with and without
electrolyte or acid-base abnormalities did not differ with respect to age, sex
distribution, and whole blood glucose. Blood tonicity was lower and poor fluid
intake, frequent regurgitations or loose stools more common among infants with
electrolyte or acid-base abnormalities. CONCLUSIONS: This prospective cross
sectional study shows that electrolyte or acid-base abnormalities, most
frequently hyponatremia, occur in approximately 3 quarters of infants with acute
pyelonephritis.
PMID- 28697496
TI - Spatially Resolved Spectral Sensitivities as a Potential Read-out Parameter in
Clinical Gene Therapeutic Trials.
AB - PURPOSE: Spatially resolved functional assessment of rods and cones under
photopic and scotopic conditions is desirable to evaluate the treatment outcome
of gene therapeutic applications in inherited retinal disorders, such as early-
onset severe retinal dystrophy (EOSRD) or achromatopsia. METHODS: A sample of 3
healthy subjects, 6 patients with RPE65 deficiency (aged 11-45 years), and 3
patients with cone dysfunction disorders underwent spectral sensitivity testing
(SST) under conditions of dark and light adaptation using a Humphrey Field
Analyzer modified perimeter. RESULTS: SST in healthy subjects revealed
sensitivity curves corresponding well with the CIE (International Commission on
Illumination) standard fundamentals. Absence of cone function was observed in
patients with cone dysfunction disorders. In patients with RPE65 mutations, SST
under conditions of both dark and light adaptation revealed similar curves at
typical cone sensitivities. S cone-related thresholds were diminished in young
patients (11-14 years) and absent in adults (19 years and over). CONCLUSION: In
the present study, residual vision was cone mediated both under photopic and
scotopic conditions in young patients with EOSRD associated with RPE65 mutations,
but S cone function was severely reduced early on. In rod monochromats, vision
was rod mediated both under conditions of dark and light adaptation. These
observations are important for ongoing and future clinical trials employing gene
therapeutic strategies in both rod-cone dystrophies and achromatopsia.
PMID- 28697497
TI - One-Year Outcomes following Intravitreal Aflibercept for Polypoidal Choroidal
Vasculopathy in Japanese Patients: The APOLLO Study.
AB - PURPOSE: To evaluate 1-year outcomes of intravitreal injections of aflibercept
(IVA) in Japanese polypoidal choroidal vasculopathy (PCV) patients. METHODS: In
this prospective, open-label, single-arm multicenter clinical trial, treatment
naive PCV patients received IVA (2.0 mg) every 2 months, after 3 initial monthly
doses. The primary endpoint assessed was the proportion of patients maintaining
baseline best-corrected visual acuity (BCVA) at 1 year. RESULTS: Fifty eyes with
PCV were included in the study. BCVA was maintained or improved in 97.6% of the
patients. Mean logMAR BCVA at baseline was 0.33, and had improved to 0.12 logMAR
1 year after the initiation of aflibercept treatment (p < 0.001). Mean central
foveal thickness decreased from 356 to 239 MUm (p < 0.001). Complete regression
of polypoidal lesions was seen in 72.5% after 1 year of treatment. CONCLUSIONS:
One year of IVA resulted in stabilization of BCVA and anatomical improvement in
Japanese PCV patients.
PMID- 28697498
TI - Effect of Histone Deacetylase HDAC3 on Cytokines IL-18, IL-12 and TNF-alpha in
Patients with Intrahepatic Cholestasis of Pregnancy.
AB - BACKGROUND/AIMS: The pathogenesis of intrahepatic cholestasis of pregnancy (ICP)
is poorly understood. OBJECTIVE: This study aimed to explore the possible effect
of HDAC3 (histone deacetylase) on cytokines IL-18, IL-12 and TNF-alpha in ICP.
METHODS: Serum levels of cytokines IL-18, IL-12 and TNF-alpha, bile acids and
hepatic function parameters were measured. The expression of HDAC3 in the
placenta was determined by immunohistochemistry (IHC), western blotting and RT
PCR. RESULTS: IL-18, IL-12 and TNF-alpha serum levels were significantly higher
in the severe ICP group than in the mild ICP group and the control group, and the
difference between the mild ICP group and control group was not significant.
HDAC3 protein expression was identified in the nucleus of the placental
trophoblast by IHC. HDAC3 mRNA and protein expression were significantly lower in
the ICP groups (mild ICP and severe ICP groups) than in the control groups, and
no significant difference was found between the mild ICP and severe ICP groups.
CONCLUSIONS: The low expression of HDAC3 and overexpession of inflammatory
cytokines (IL-18, IL-12 and TNF-alpha) in ICP may be involved in liver cell
apoptosis. We suspect that HDAC3 may play an important role in the
pathophysiology of ICP.
PMID- 28697499
TI - Perinatal Outcomes of Non-Primary Maternal Cytomegalovirus Infection: A 15-Year
Experience.
AB - OBJECTIVE: To evaluate perinatal outcomes in case of non-primary maternal
cytomegalovirus (CMV) infection. METHODS: We performed a retrospective cohort
study of pregnant women with active CMV infection referred to our unit over a 15
year period (January 2000 to December 2014). Non-primary infection was diagnosed
on the basis of the results of confirmatory serological and virological tests
(avidity test, immunoblotting, real-time PCR-DNA). The vertical transmission rate
and the percentage of symptomatic congenital infection were determined in this
group of patients. RESULTS: A total of 205 pregnant women were enrolled.
Congenital infection occurred in 7 (3.4%) fetuses/neonates. Symptomatic disease
was present at birth in 3 of the 7 congenitally infected neonates (1.5%). Two out
of 3 symptomatic newborns presented a pathologic second-trimester ultrasound
scan. CONCLUSION: Maternal immunity offers substantial protection against
intrauterine transmission of CMV infection, but not against disease once the
fetus is infected.
PMID- 28697500
TI - Cx43- and Smad-Mediated TGF-beta/ BMP Signaling Pathway Promotes Cartilage
Differentiation of Bone Marrow Mesenchymal Stem Cells and Inhibits Osteoblast
Differentiation.
AB - BACKGROUND/AIMS: The aim of this study was to investigate the influence of Cx43-
and Smad-mediated TGF-beta/BMP signaling pathway on the differentiation of bone
marrow mesenchymal stem cells (BMSCs) into cartilage and inhibition of
ossification. METHODS: BMSCs of Wistar rats were cultured and assigned into 5
groups for transfection with adenoviruses. Quantitative real-time polymerase
chain reaction (qRT-PCR) and Western blotting were employed to detect mRNA and
protein expressions of target genes. The condition of cartilage and ossification
were measured by a series of staining methods. Subcutaneous injection of
mesenchymal stem cells (MSCs) into nude rats was performed. RESULTS: After
transfection, compared to the AdGFP group, the corresponding target mRNAs were
overexpressed in the AdBMP2, AdSmad1, AdCx43 + AdSmad1 and AdCx43 + AdSmad1 +
AdBMP2 groups, and overexpression of BMP2 at the mRNA and protein expression was
observed in the AdSmad1 and AdCx43 + AdSmad1 groups. The mRNA expressions of
aggrecan (ACAN) and collagen type II alpha 1 (Col2a1), the glycosaminoglycan
content of the extracellular matrix and the expression of type II collagen,
Col2a1, osteopontin (OPN) and osteocalcin (OC) were higher in the AdBMP2,
AdSmad1, AdCx43 + AdSmad1 and AdCx43 + AdSmad1 + AdBMP2 groups than in the AdGFP
group; alkaline phosphatase (ALP) activity and mRNA and protein expressions of
Runx2 were also higher in these groups than in the AdGFP group. Heterotopic
osteogenesis tests demonstrated evident cartilage differentiation ability in the
AdCx43 + AdSmad1 + AdBMP2 groups. In comparison, the AdCx43 + AdSmad1 and AdSmad1
groups exhibited weaker cartilage differentiation abilities. CONCLUSION: Cx43 and
Smad1 promote BMP-induced cartilage differentiation of BMSCs and inhibit
osteoblast differentiation, which provide a new strategy for cartilage tissue
engineering using exogenous Cx43 and Smad1.
PMID- 28697501
TI - Born Small for Gestational Age and Poor School Performance - How Small Is Too
Small?
AB - AIM: To assess the relationship between severity of small for gestational age
(SGA) and the risk of poor school performance, and to investigate whether adult
stature modifies this risk. METHODS: 1,088,980 Swedish children born at term
between 1973 and 1988 were categorized into severe SGA (less than -3 standard
deviations (SD) of expected birth weight), moderate SGA (-2.01 to -3 SD), mild
SGA (-1.01 to -2 SD), and appropriate for gestational age (-1 to 0.99 SD). The
risk of poor school performance at the time of graduation from compulsory school
(grades <10th percentile) was calculated using unconditional logistic regression
models and adjusted for socio-economic factors. In a sub-analysis, we stratified
boys by adult stature, and adjusted for maternal but not paternal height.
RESULTS: All SGA groups were significantly associated with an increased risk of
poor school performance, with adjusted odds ratios and 95% confidence intervals
ranging from 1.85 (1.65-2.07) for severe SGA to 1.25 (1.22-1.28) for mild SGA. In
the sub-analysis, all birth weight groups were associated with an increased risk
of poor school performance among boys with short stature compared to those with
non-short stature. CONCLUSION: Mild SGA is associated with a significantly
increased risk of poor school performance, and the risk increases with severity
of SGA. Further, this risk diminishes after adequate catch-up growth.
PMID- 28697502
TI - Predictors of Outcome in Acute Stroke Patients: Are They Reliable and Potentially
Useful?
PMID- 28697503
TI - Update of Sepsis in the Intensive Care Unit.
AB - Sepsis, the most common cause of admission to an intensive care unit (ICU), has
had an increased incidence and prevalence over the last years with a simultaneous
decrease in its short-term mortality. Sepsis survivors are more frequently
discharged from hospital and often experience long-term outcomes such as late
mortality, immune dysfunction, secondary infections, impaired quality of life,
and unplanned readmissions. Early recognition and management of sepsis have
challenged emergency care and critical care physicians and nurses. New sepsis
definitions were produced and the Surviving Sepsis Campaign (SSC) 2016 was
updated recently. Although hospital readmissions after sepsis are common,
associated risk factors and how to manage patients who survive an episode of
sepsis still need clarification. The immune dysfunction caused by sepsis/septic
shock is complex, persistent, affects inflammatory and anti-inflammatory systems,
and might be associated with long-term outcomes of sepsis. Several randomized
controlled trials (RCT) that analyzed new (and old) interventions in
sepsis/septic shock are discussed in this review in parallel with the SSC 2016
recommendations and other guidelines when relevant. RCTs addressing incidence,
treatment, and prevention of important sepsis-associated organ dysfunction such
as the acute respiratory distress syndrome, acute kidney injury, and brain
dysfunction are highlighted. Finally, we briefly discuss the need for novel
targets, predictive biomarkers, and new designs of RCTs in sepsis.
PMID- 28697504
TI - Effects of a Training Program Involving Body Cooling on Physical and Cognitive
Capacities and Quality of Life in Multiple Sclerosis Patients: A Pilot Study.
AB - OBJECTIVE: Two methods using exercise and body cooling could influence the well
being of patients with multiple sclerosis (PwMS). The aim of this study was to
determine whether wearing a cooling vest during a physical training program could
increase the cognitive and physical capacities and quality of life in PwMS.
METHODS: Eighteen PwMS (49.6 +/- 8 years; Expanded Disability Status Score 5.0 +/
1.0) were randomly assigned to a cooling or control group. PwMS underwent a 7
week physical training program. In the cooling group, PwMS wore a cooling vest
during each training session, whereas in the control group, PwMS wore a cotton T
shirt. Before and after the training program, both groups completed the Isaacs
Set Test (IST), Trail Making Test A-B (TMT A-B), SEP-59, Multidimensional Fatigue
Inventory and performed a 6-minute walk test (6MWT). RESULTS: The cooling group
showed significantly (p < 0.05) improved performance for IST, TMT A and 6MWT.
Their emotional well-being and cognitive functions investigated in SEP-59 were
significantly (p < 0.05) improved, and general and physical fatigue significantly
(p < 0.05) decreased. CONCLUSIONS: This physical training program combined with a
cooling strategy could have a significant positive influence on both cognitive
and physical performances, perceived fatigue and emotional well-being in heat
sensitive PwMS.
PMID- 28697505
TI - The Importance of 11alpha-OH, 15-oxo, and 16-en Moieties of 11alpha-Hydroxy-15
oxo-kaur-16-en-19-oic Acid in Its Inhibitory Activity on Melanogenesis.
AB - Cosmetic industries have an interest in exploring and developing materials that
have the potential to regulate melanin synthesis in human skin. Although melanin
protects the skin from ultraviolet irradiation, excess melanin can be
undesirable, particularly on the face where spots or freckles are associated with
an appearance of aging. In this study, we found that ent-11alpha-hydroxy-15-oxo
kaur-16-en-19-oic acid (11alpha-OH KA) in Pteris dispar Kunze strongly inhibited
melanin synthesis by suppressing tyrosinase gene expression. The melanogenic
transcription factor microphthalmia-associated transcription factor (MITF) is
required for this suppression. However, 11alpha-OH KA did not modulate the
expression level or activity of MITF. Structure-activity relationship analyses
suggested that the 11alpha-OH, 15-oxo, and 16-en moieties of 11alpha-OH KA are
essential for the suppression of melanin synthesis. On the other hand, the 19
COOH moiety is important for preventing cellular toxicity associated with 11alpha
OH KA and its related compounds. These results suggest that 11alpha-OH KA is an
attractive target for potential use in the production of cosmetic items.
PMID- 28697506
TI - Evaluation of the Efficacy and Safety of Laser versus Cold Knife Urethrotomy in
the Management of Patients with Urethral Strictures: A Systematic Review and Meta
Analysis of Randomized Clinical Trials.
AB - INTRODUCTION: Urethral strictures generate great morbidity. Two procedures have
been described for their management - laser and cold knife techniques - which are
still widely used. We aim to assess the safety and efficacy of laser versus cold
knife urethrotomy. MATERIALS AND METHODS: We conducted a systematic search of the
literature using MEDLINE, EMBASE, LILACS and Cochrane databases and gray
literature. Primary outcomes were urethral stricture recurrence, time-to
recurrence and complication rate. Secondary outcomes were quality of life and
maximum urinary flow rate (Qmax). Data analysis was obtained using Review Manager
5.2. RESULTS: Out of 137 publications, 4 articles were included in the meta
analysis. At 3 months, the recurrence rate was similar in both groups (0.55, 95%
CI 0.18-1.66), but at 6 and 12 months, it was significantly lower in the laser
urethrotomy group (0.39, 95% CI 0.19-0.81 and 0.44, 95% CI 0.26-0.75). The
analysis of Qmax at 6 months post-intervention suggested a greater improvement in
the laser urethrotomy group. A qualitative analysis showed that complications in
both procedures were minor and infrequent. CONCLUSIONS: Laser urethrotomy has a
lower recurrence rate at 6 and 12 months compared to cold knife urethrotomy.
Complications in both procedures are minor and infrequent. Results should be
interpreted cautiously, since they were evaluated only for a short term.
PMID- 28697507
TI - [On the assessment of spontaneous respiratory changes in respiration
olfactometry].
AB - INTRODUCTION: Alterations of breathing pattern evoked by odors are used to proof
the integrity of the olfactory system in the sense of respiratory olfactometry.
Spontaneous breathing changes normally cannot be distinguished from evoked
changes. It is therefore necessary to repeatedly apply stimuli with a pure
odorant during tidal breathing, randomized with neutral air, to detect a majority
of olfactory-evoked respiratory changes. METHODS: In 26 adult normosmics, 15 H2S
and 15 neutral air stimuli (duration: 2 sec) were randomly applied with an
interstimulus interval of at least 1 minute, using a flow olfactometer. Before
stimulation, the respiration was not allowed to scatter significantly (variation
coefficient of the duration of inspiration (DIN) and expiration (DEX) <=0.1). A
respiratory response was fulfilled when respectively DIN and DEX of the stimulus
breath exceeded the double standard deviation of the same parameters in the five
preceding respiratory cycles. The number of reactions was normalized to the
number of stimuli and to the off-line as regularly calculated respiratory
complexes and thus reaction indices were formed. RESULTS: H2S stimuli clearly
evoked more respiratory changes than neutral air stimuli. DIN and DEX decreased
with olfactory stimulation more frequently than with an application of neutral
air. Extensions of DIN and DEX were not different between the two stimulus
qualities. CONCLUSIONS: Only the randomized nasal stimulation with an odor and a
blank makes the respiration-olfactometry meaningful.
PMID- 28697508
TI - [Editor's Comment].
PMID- 28697509
TI - [Not Available].
PMID- 28697510
TI - [Not Available].
PMID- 28697511
TI - [Not Available].
PMID- 28697512
TI - ?
PMID- 28697513
TI - [Prevalence, Risk Factors and Diagnostics of Hearing Impairment in Preterm
Infants].
AB - Introduction: The preterm birth is clearly associated with increased risk of
developing congenital hearing impairment. Therefore, special attention must be
paid to the postnatal control of auditory function in all preterm infants. The
present work investigates if the latest scientific findings regarding prevalence,
clinical diagnostics, therapy and risk factors of hearing impairment in premature
infants are regularly implemented in daily practice. Methods: At the department
of phoniatrics and pediatric audiology of the University Hospital of Magdeburg,
the treatment data of 126 preterm children born between 2006 and 2011 were
evaluated retrospectively. The additional analysis of all records available at
the screening center (n=67 640) covering this period enables drawing conclusions
on the total number and prevalence of hearing impairment in preterm infants in
Saxony-Anhalt. Results: Almost all premature babies, like mature newborns,
underwent postnatal hearing screening of both ears. The data analysis shows that
the practical implementation often does not comply with the guideline of the G-BA
(Gemeinsamer Bundesausschuss) in all details. For example, the recommended
screening method for preterm infants (AABR) or the screening and treatment timing
are not always applied in accordance with the guidelines of the G-BA. Discussion:
Assessment of the practical implementation of universal newborn hearing screening
was planned at the time of the introduction of the hearing screening program by
the G-BA. As a part of this investigation, the practical care of vulnerable
groups such as preterm infants must be given special attention. Based on the
collected data, the diagnostics and therapy should be unified. Regardless of the
maternity clinic where the infants were born, there should be the same
opportunity for early diagnosis and thus for prognostically better treatment of
congenital hearing impairment. Rapid postnatal fitting with hearing aid can
stimulate the maturation of the central auditory system and potentially help to
avoid problems of hearing and speech development.
PMID- 28697514
TI - [Cranial Nerve Paralysis after Functional Endoscopic Sinus Surgery. Case Report].
PMID- 28697515
TI - [Recurrent Sialadenitis of both Parotid Glands in Adolescence].
PMID- 28697516
TI - ?
PMID- 28697517
TI - [Cochlear Implants in Children and Adults].
AB - About 4000 patients receive a cochlear implant in Germany every year. Adults have
become the main group for cochlear implantation candidacy.Elderly people with
progressive and profound hearing loss experienced high communication restraints
due to the limits of conventional hearing aids in the past. Nowadays cochlear
implants can be offered as a well-established extension to the supply chain of
hearing systems. The option of cochlear implantation for children with profound
hearing impairment has led to a paradigm shift in hearing rehabilitation.
However, there is still great variability in spoken language outcomes in CI
children. These range from communicative and linguistic competencies similar to
normal hearing children to clearly limited receptive and productive language
skills. Besides age of implantation and the quality of previous auditory
stimulation, there are additional factors that likely influence the outcome after
cochlea implantation. Among them are the quality of caregivers' linguistic input
and an intensive post-operative rehabilitation and intervention program. Ideally,
children with CI are included into mainstream educational settings. Considering
the high incidence of additional disabilities in children with hearing loss, it
seems obvious that this goal cannot be achieved by all implanted children.
Therefore, highly complex and individualized rehabilitation concepts are needed,
which, in addition to oral language intervention programs, include total
communication approaches as well.
PMID- 28697518
TI - ?
PMID- 28697519
TI - ?
PMID- 28697520
TI - [Correction: Quality Controls in Hospitals by MDK Hessen: A Practice Report of
Experiences and Outlook].
PMID- 28697521
TI - [Measures for Overcoming Barriers to Palliative Care of Patients with Chronic
Heart Failure: A Delphi Method].
AB - Patients with chronic heart failure receive less palliative care than those
suffering from malignant diseases, even though they experience a similar disease
burden. Studies found that this might be caused by the cyclic course of disease,
which makes determination of the appropriate time difficult, lack of knowledge
regarding content and structure of palliative care, and insufficient
interprofessional communication. However, research suggests that patients with
chronic heart failure benefit from palliative care. In this study, academic
experts and experienced clinical practitioners developed measures in order to
overcome the previously identified barriers. Furthermore, measures were evaluated
regarding their relevance and practicability. In a next step, measures rated as
both relevant and practical were ranked regarding their importance. Those
perceived as important and practical mainly focused on better education for and
better cooperation between professionals.
PMID- 28697522
TI - Childhood Vaccination Against Seasonal Influenza to Reduce the Overall Burden of
Disease: Ethical Perspectives.
AB - Introduction Childhood immunisation against seasonal influenza promises to reduce
the burden of disease through herd immunity. The option of intranasal vaccination
seemed to offer a more acceptable vaccination for children, as they are perceived
to be less invasive. Yet, intranasal vaccines have been recently proven not to be
as effective as presumed. In Germany, contradictory recommendations of the
Standing Committee on Vaccination (STIKO) first, to use and then, in October
2016, not use these vaccines have been issued for the 2016-2017 season, whereas
recommendations not to use them were already issued in the USA (CDC, ACIP). This
controversy spurs the discussion of immunisation programmes for children again.
Despite studies discussing the effectiveness of a comprehensive immunisation
programme targeting children also in the German and wider European context, an
accompanying ethical discussion is missing. Methodology We discuss several policy
options from different key ethical perspectives that are widely used in public
health: if seasonal influenza vaccination should be intensively offered to or
even made mandatory for children to decrease the societal burden of the disease.
Results Various ethical perspectives reflect the question how to balance
individual autonomy, personal benefit and population benefit differently.
Discussion A convincing justification for suggestions on immunisation policies
has to balance norms anchored in different ethical theories. There are good
reasons to offer immunisation programmes against seasonal influenza to children,
using a voluntary, possibly incentive-based approach.
PMID- 28697523
TI - [Assessment of IDC-Pal as a Diagnostic Tool for Family Physicians to Identify
Patients with Complex Palliative Care Needs in Germany: a Pilot Study].
AB - BACKGROUND: Palliative medicine is an essential component of the health care
system. Basic palliative care should be provided by primary care services (family
physician and home nursing) with palliative-medical basic qualification. Often it
is very difficult to identify patients that would profit from a specialized
palliative care team. For the evaluation of the case complexity of a palliative
patient, we present a Spanish diagnostic tool IDC-Pal, which tries to specify
when, why and where a palliative patient should be referred. The aims of this
study were the translation and cultural adaptation of the diagnostic tool for
complexity in palliative care IDC-Pal to the German language, and the measurement
of its feasibility and face validity. METHODS: During the first phase, a forward
backward translation with linguistic and cultural adaptation of the tool IDC-Pal
as well as the validation of its content by a review committee was performed.
During the second phase, the preliminary version of the tool was tested by 38
family physicians that were asked for a qualitative assessment using a 10-points
Likert scale (1 = "strongly disagree" and 10 = "totally agree"). Finally, a
definitive version was developed. RESULTS: The translation and adaptation were
achieved without major problems. Both feasibility and apparent validity of the
tool IDC-Pal were rated as high. The mean response in the Likert scale was 7.79,
with a SD of 0.36. Participants strongly agreed on the apparent validity of the
tool with a mean of 7.82 and a SD of 0.26 and on its feasibility with a mean of
7.79, and a SD of 0.39. CONCLUSIONS: A conceptually, culturally and
linguistically equivalent version of the original instrument IDC-Pal was
obtained. German family physicians agreed on the usability of IDC-Pal as a tool
for rating the case complexity of palliative patients. These results indicate
that physicians in Bavaria and eventually in Germany could benefit of the full
validation of IDC-Pal.
PMID- 28697524
TI - [Health Science Research with Primary Care Routine Data From Electronic Patient
Records: the BeoNet Registry].
AB - Reliable current information is needed for daily patient care and the health
system, but comprehensive data, especially from primary care, are scarce and/or
hard to access. The BeoNet Register-Database (BNR) aims to depict quality of
medical care in Germany using routine data and with no additional documentation
or costs for GPs. Registry design, data structure and database use will be
demonstrated using chronic obstructive lung disease (COPD) as an example. The BNR
is moving through pilot- and roll-out phases. Participating practices provide
standardized information about (1) master data (2) practice profile (3)
infrastructure and documentation systems. The routinely documented data will be
pseudonymized before transmission via standardized secure interfaces to the
registry database. Practices can participate in studies in cooperation with BNR
if informed consent is obtained from the patients. The registry data will be
linked with questionnaires on health care utilization, quality of life and
disease-specific parameters. Researchers and physicians can access quasi
anonymized data in specific datasets extracted from the registry. Regular
automatic data quality checks and feedback from GPs, patients and researchers
enhance the quality of the registry. Performance and data analysis are
continuously optimized. The data security concept has been approved and ethical
approval is on hand. GPs, pediatricians and pneumologists from Hanover, Munich
and Heidelberg participated in the pilot phase. The registry database currently
holds 98497 patient IDs and related information. BNR contains more than the
standard billing data collected by health insurers. The data are applicable to a
wide range of health practices, health care and economics and disease development
questions. Questionnaires have been generated, tested and are being distributed.
First descriptive analyses of prevalence, age and gender have been performed.
Quality and validity checks have been implemented. 2016 marks the roll-out phase
of the BNR. Further recruitment of practices throughout Germany, data linkage
with additional questionnaires, recruitment of patients for health care research
projects, quality checks and data analysis of disease-specific costs and health
related quality of life in COPD are progressing with the overall aim of improving
pulmonary healthcare strategies. The floor is now open for retro- and prospective
cross-sectional and longitudinal studies.
PMID- 28697525
TI - [What Enhances Teachers' Health at Inclusive Primary Schools? A Mixed-Methods
Approach].
AB - AIM: Teachers' suggestions to enhance their health at inclusive primary schools
("Schwerpunktgrundschulen") were analyzed by quantitative content analysis taking
personal or job-related parameters of effort and strain into consideration.
METHOD: The paper and pencil cross-sectional study was conducted by Institut fur
Lehrergesundheit (IFL) between August 2013 and April 2015 at 14 schools in
Rhineland-Palatinate. Overall response rate was 46.3% (143/309 teachers). The
answers to the open-ended question "Which concrete job-related measures would
enhance your wellbeing or health situation at your work place?" was categorized
and quantified. An analysis of the item-non-response was undertaken. The aim was
to identify by logistic regression, personal or job-related parameters of effort
or strain associated with a specific category. RESULTS: Data from 143 teachers
were analyzed. 79 teachers made 362 suggestions to enhance the health situation
at their work place. Making a suggestion was not related to socio-demographic
parameters. 33.6% of the teachers addressed physical environmental conditions of
work, e. g., climatic or acoustic conditions or the availability of space for
recreation. 29.4% of the teachers made suggestions concerning human resource
strategy (e. g., "double teaching"). 9.1% of the teachers referred to aspects of
relationships with colleagues. After regression analysis, there were
relationships between suggestions of single categories and specific job-related
parameters of effort. Furthermore, teachers under (high) strain - here: teachers
who (very) strongly experienced their work as hazardous to health - showed
significantly higher odds to make suggestions of the categories "Colleagues" (aOR
3.71; 95%CI 1.00-13.76) or "External Support" (e. g., "supervision") (aOR 3.92;
95%CI 1.15-13.41) than teachers experiencing less stress. CONCLUSIONS: Teachers
of inclusive primary schools are ready to take active part in health-related
organizational development. The development of problem- and group-specific
measures of intervention will be facilitated by the combined analysis of
qualitative and quantitative data.
PMID- 28697526
TI - [Quality Indicators of Primary Health Care Facilities in Austria].
AB - Background The strengthening of primary health care is one major goal of the
current national health reform in Austria. In this context, a new
interdisciplinary concept was developed in 2014 that defines structures and
requirements for future primary health care facilities. Objective The aim of this
project was the development of quality indicators for the evaluation of the
scheduled primary health care facilities in Austria, which are in accordance with
the new Austrian concept. Methods We used the RAND/NPCRDC method for the
development and selection of the quality indicators. We conducted systematic
literature searches for existing measures in international databases for quality
indicators as well as in bibliographic databases. All retrieved measures were
evaluated and rated by an expert panel in a 2-step process regarding relevance
and feasibility. Results Overall, the literature searches yielded 281 potentially
relevant quality indicators, which were summarized to 65 different quality
measures for primary health care. Out of these, the panel rated and accepted 30
measures as relevant and feasible for use in Austria. Five of these indicators
were structure measures, 14 were process measures and the remaining 11 were
outcome measures. Based on the Austrian primary health care concept, the final
set of quality indicators was grouped in the 5 following domains: Access to
primary health care (5), quality of care (15), continuity of care (5),
coordination of care (4), and safety (1). Conclusion This set of quality measures
largely covers the four defined functions of primary health care. It enables
standardized evaluation of primary health care facilities in Austria regarding
the implementation of the Austrian primary health care concept as well as
improvement in healthcare of the population.
PMID- 28697527
TI - [Family Health Teams in Ontario: Ideas for Germany from a Canadian Primary Care
Model].
AB - The German healthcare system is struggling with fragmentation of care in the face
of an increasing shortage of general practitioners and allied health
professionals, and the time-demanding healthcare needs of an aging, multimorbid
patient population. Innovative interprofessional, intersectoral models of care
are required to ensure adequate access to primary care across a variety of rural
and urban settings into the foreseeable future. A team approach to care of the
complex multimorbid patient population appears particularly suitable in
attracting and retaining the next generation of healthcare professionals,
including general practitioners. In 2014, the German Advisory Council on the
Assessment of Developments in the Health Care System highlighted the importance
of regional, integrated care with community-based primary care centres at its
core, providing comprehensive, population-based, patient-centred primary care
with adequate access to general practitioners for a given geographical area. Such
centres exist already in Ontario, Canada; within Family Health Teams (FHT),
family physicians work hand-in-hand with pharmacists, nurses, nurse
practitioners, social workers, and other allied health professionals. In this
article, the Canadian model of FHT will be introduced and we will discuss which
components could be adapted to suit the German primary care system.
PMID- 28697528
TI - Who will be the Radiologists of Tomorrow? A survey of radiology during the
"Practical Year" in Germany.
AB - Purpose Aim of our study was to evaluate the motivation of medical students in
their final year of medical school to choose radiology for further specialization
by means of a Germany-wide survey. Materials and Methods The survey was performed
during the 2015/16 semester among German medical students in their four months
radiology elective during the final year. Invitations for the study were
distributed by the Student Secretariats of each university. The survey was web
based with EvaSys 7.0 software. Questions on radiology contents during medical
studies and "practical year" were part of the survey. Plans for residency and
possible advantages and disadvantages of radiology as medical specialty were
inquired. Descriptive statistics and group comparisons were used as analysis
methods. Results 89 students participated in the survey at the beginning and 60
students at the end of the practical year. Of these 39 students could be
identified who answered both questionnaires. Most students were satisfied with
their final year radiology elective (mean 1.8 on a range from 1 to 5).
Nevertheless, they criticized mentoring during routine work (mean 2.1) and a lack
of educational courses (mean 2.1). Most students (83 %) were uncertain about
their residency choice at the beginning of their "practical year" and about one
fifth changed their plans. From the students' point of view main advantages of
radiology included contact with many other clinical disciplines (87 %) and the
working conditions (68 %). The reduced patient contact (42 %), the large amount
of work at a computer (43 %), and the dependency on referring physicians (42 %)
were regarded as the main disadvantages. The students regarded the way radiology
is taught during the studies as not practical enough. With regard to radiology
the majority of students (63 %) felt poorly prepared for their future work.
Conclusion The "practical year" is important regarding the choice of future
specialization. There was a high degree of satisfaction with the "practical year"
in radiology. The mentoring during routine work and a lack of educational courses
was mildly criticized. These factors provide room for improvement to foster
students' interest in radiology. Key Points . The "practical year" is important
regarding the choice of further specialization.. . Criticisms of radiology in the
"practical year" were mentoring and courses.. . Students feel poorly prepared for
their future work regarding practical radiological skills.. Citation Format .
Dettmer S, Fischer V, Paebetaens C et al. Who will be the Radiologists of
Tomorrow? A survey of radiology during the "Practical Year" in Germany. Fortschr
Rontgenstr 2017; 189: 967 - 976.
PMID- 28697529
TI - Correction of Pelvic Tilt and Pelvic Rotation in Cup Measurement after THA - An
Experimental Study.
AB - Purpose Accurate assessment of cup orientation on postoperative pelvic
radiographs is essential for evaluating outcome after THA. Here, we present a
novel method for correcting measurement inaccuracies due to pelvic tilt and
rotation. Method In an experimental setting, a cup was implanted into a dummy
pelvis, and its final position was verified via CT. To show the effect of pelvic
tilt and rotation on cup position, the dummy was fixed to a rack to achieve a
tilt between + 15 degrees anterior and -15 degrees posterior and 0 degrees to
20 degrees rotation to the contralateral side. According to Murray's definitions
of anteversion and inclination, we created a novel corrective procedure to
measure cup position in the pelvic reference frame (anterior pelvic plane) to
compensate measurement errors due to pelvic tilt and rotation. Results The cup
anteversion measured on CT was 23.3 degrees ; on AP pelvic radiographs, however,
variations in pelvic tilt (+/- 15 degrees ) resulted in anteversion angles
between 11.0 degrees and 36.2 degrees (mean error 8.3 degrees +/- 3.9 degrees
). The cup inclination was 34.1 degrees on CT and ranged between 31.0 degrees
and 38.7 degrees (m. e. 2.3 degrees +/- 1.5 degrees ) on radiographs. Pelvic
rotation between 0 degrees and 20 degrees showed high variation in radiographic
anteversion (21.2 degrees -31.2 degrees , m. e. 6.0 degrees +/- 3.1 degrees ) and
inclination (34.1 degrees -27.2 degrees , m. e. 3.4 degrees +/- 2.5 degrees ).
Our novel correction algorithm for pelvic tilt reduced the mean error in
anteversion measurements to 0.6 degrees +/- 0.2 degrees and in inclination
measurements to 0.7 degrees (SD+/- 0.2). Similarly, the mean error due to pelvic
rotation was reduced to 0.4 degrees +/- 0.4 degrees for anteversion and to 1.3
degrees +/- 0.8 for inclination. Conclusion Pelvic tilt and pelvic rotation may
lead to misinterpretation of cup position on anteroposterior pelvic radiographs.
Mathematical correction concepts have the potential to significantly reduce these
errors, and could be implemented in future radiological software tools. Key
Points . Pelvic tilt and rotation influence cup orientation after THA. . Cup
anteversion and inclination should be referenced to the pelvis. . Radiological
measurement errors of cup position may be reduced by mathematical concepts.
Citation Format . Schwarz TJ, Weber M, Dornia C et al. Correction of Pelvic Tilt
and Pelvic Rotation in Cup Measurement after THA - An Experimental Study.
Fortschr Rontgenstr 2017; 189: 864 - 873.
PMID- 28697530
TI - Modern Cartilage Imaging of the Ankle.
AB - Background Talar osteochondral lesions are an important risk factor for the
development of talar osteoarthritis. Furthermore, osteochondral lesions might
explain persistent ankle pain. Early diagnosis of accompanying chondral defects
is important to establish the optimal therapy strategy and thereby delaying or
preventing the onset of osteoarthritis. The purpose of this review is to explain
modern cartilage imaging with emphasis of MR imaging as well as the discussion of
more sophisticated imaging studies like CT-arthrography or functional MR imaging.
Methods Pubmed literature search concerning: osteochondral lesions, cartilage
damage, ankle joint, talus, 2 D MR imaging, 3 D MR imaging, cartilage MR imaging,
CT-arthrography, cartilage repair, microfracture, OATS, MACT. Results and
Conclusion Dedicated MR imaging protocols to delineate talar cartilage and the
appearance of acute and chronic osteochondral lesions were discussed. Recent
developments of MR imaging, such as isotropic 3 D imaging that has a higher
signal-to noise ratio when compared to 2 D imaging, and specialized imaging
methods such as CT-arthrography as well as functional MR imaging were introduced.
Several classifications schemes and imaging findings of osteochondral lesions
that influence the conservative or surgical therapy strategy were discussed. MRI
enables after surgery the non-invasive assessment of the repair tissue and the
success of implantation. Key points . Modern MRI allows for highly resolved
visualization of the articular cartilage of the ankle joint and of subchondral
pathologies.. . Recent advances in MRI include 3 D isotropic ankle joint imaging,
which deliver higher signal-to-noise ratios of the cartilage and less partial
volume artifacts when compared with standard 2 D sequences.. . In case of
osteochondral lesions MRI is beneficial for assessing the stability of the
osteochondral fragment and for this discontinuity of the cartilage layer is an
important factor.. . CT-arthrography can be used in case of contraindications of
MRI and in unclear MRI findings as further diagnostic approach.. Citation Format
. Weber MA, Wunnemann F, Jungmann PM et al. Modern Cartilage Imaging of the
Ankle. Fortschr Rontgenstr 2017; 189: 945 - 956.
PMID- 28697531
TI - Pain Reduction in the Recanalization of Chronic Iliofemoral Venous Occlusion with
a New Scoring Balloon: A Retrospective Series in 10 Consecutive Patients.
PMID- 28697532
TI - ?
PMID- 28697533
TI - Predictors of operative time during radical retropubic prostatectomy and robot
assisted laparoscopic prostatectomy.
AB - OBJECTIVES: To better predict operative time using patient/surgical
characteristics among men undergoing radical retropubic prostatectomy or robot
assisted laparoscopic prostatectomy in order to achieve more efficient operative
scheduling and potentially decrease costs in the Veterans Health System. METHODS:
We analyzed 2619 men treated with radical retropubic prostatectomy (n = 2005) or
robot-assisted laparoscopic prostatectomy (n = 614) from 1993 to 2013 from six
Veterans Affairs Hospitals in the Shared Equal Access Regional Cancer Hospital
database. Age, body mass index, race, biopsy Gleason, prostate weight, undergoing
a nerve-sparing procedure or lymph node dissection, and hospital surgical volume
were analyzed in multivariable linear regression to identify predictors of
operative time and to quantify the increase/decrease observed. RESULTS: In men
undergoing radical retropubic prostatectomy, body mass index, black race,
prostate weight and a lymph node dissection all predicted longer operative times
(all P <= 0.004). In men undergoing robot-assisted laparoscopic prostatectomy,
biopsy Gleason score and a lymph node dissection were associated with increased
operative time (P <= 0.048). In both surgical methods, a lymph node dissection
added 25-40 min to the operation. Also, in both, each additional operation per
year per center predicted a 0.80-0.89-min decrease in operative time (P <=
0.001). CONCLUSIONS: Overall, several factors seem to be associated with
quantifiable changes in operative time. If confirmed in future studies, these
findings can allow for a more precise estimate of operative time, which could
decrease the overall cost to the patient and hospital by aiding in operating room
time management.
PMID- 28697534
TI - Consensus Bundle on Severe Hypertension During Pregnancy and the Postpartum
Period.
AB - Complications arising from hypertensive disorders of pregnancy are among the
leading causes of preventable severe maternal morbidity and mortality. Timely and
appropriate treatment has the potential to significantly reduce hypertension
related complications. To assist health care providers in achieving this goal,
this patient safety bundle provides guidance to coordinate and standardize the
care provided to women with severe hypertension during pregnancy and the
postpartum period. This is one of several patient safety bundles developed by
multidisciplinary work groups of the National Partnership for Maternal Safety
under the guidance of the Council on Patient Safety in Women's Health Care. These
safety bundles outline critical clinical practices that should be implemented in
every maternity care setting. Similar to other bundles that have been developed
and promoted by the Partnership, the hypertension safety bundle is organized into
four domains: Readiness, Recognition and Prevention, Response, and Reporting and
Systems Learning. Although the bundle components may be adapted to meet the
resources available in individual facilities, standardization within an
institution is strongly encouraged. This commentary provides information to
assist with bundle implementation.
PMID- 28697535
TI - Cancer stem cells and epithelial-mesenchymal transition in urothelial carcinoma:
Possible pathways and potential therapeutic approaches.
AB - There is growing evidence of the presence of cancer stem cells in urothelial
carcinoma. Cancer stem cells have the ability to self-renew and to differentiate
into all cell types of the original heterogeneous tumor. A panel of diverse
cancer stem cell markers might be suitable for simulation studies of urothelial
cancer stem cells and for the development of optimized treatment protocols. The
present review focuses on the advances in recognizing the markers of urothelial
cancer stem cells and possible therapeutic targets. The commonly reported markers
and pathways that were evaluated include CD44, CD133, ALDH1, SOX2 & SOX4, BMI1,
EZH1, PD-L1, MAGE-A3, COX2/PGE2/STAT3, AR, and autophagy. Studies on the
epithelial-mesenchymal transition-related pathways (Shh, Wnt/beta-catenin, Notch,
PI3K/Akt, TGF-beta, miRNA) are also reviewed. Most of these markers were
recognized through the expression patterns of cancer stem cell-rich side
populations. Their regulative role in the development and differentiation of
urothelial cancer stem cells was confirmed in vitro by functional analyses (e.g.
cell migration, colony formation, sphere formation), and in vivo in xenograft
experiments. Although a small number of these pathways are targeted by currently
available drugs or drugs that are the currently being tested in clinical trials,
a clear treatment approach has not been developed for most pathways. A greater
understanding of the mechanisms that control the proliferation and
differentiation of cancer stem cells is expected to lead to improvements in
targeted therapy.
PMID- 28697536
TI - Potential applications of low-energy shock waves in functional urology.
AB - A shock wave, which carries energy and can propagate through a medium, is a type
of continuous transmitted sonic wave with a frequency of 16 Hz-20 MHz. It is
accompanied by processes involving rapid energy transformations. The energy
associated with shock waves has been harnessed and used for various applications
in medical science. High-energy extracorporeal shock wave therapy is the most
successful application of shock waves, and has been used to disintegrate
urolithiasis for 30 years. At lower energy levels, however, shock waves have
enhanced expression of vascular endothelial growth factor, endothelial nitric
oxide synthase, proliferating cell nuclear antigen, chemoattractant factors and
recruitment of progenitor cells; shock waves have also improved tissue
regeneration. Low-energy shock wave therapy has been used clinically with
musculoskeletal disorders, ischemic cardiovascular disorders and erectile
dysfunction, through the mechanisms of neovascularization, anti-inflammation and
tissue regeneration. Furthermore, low-energy shock waves have been proposed to
temporarily increase tissue permeability and facilitate intravesical drug
delivery. The present review article provides information on the basics of shock
wave physics, mechanisms of action on the biological system and potential
applications in functional urology.
PMID- 28697537
TI - Novel mobility test to assess functional vision in patients with inherited
retinal dystrophies.
AB - IMPORTANCE: This novel endpoint tracks functional vision changes in patients with
inherited retinal dystrophies (IRDs) over time. BACKGROUND: The aims of the study
were to determine whether a multi-luminance mobility test (MLMT) can detect
functional vision changes over time in subjects with IRDs and to assess natural
history and potential effects of investigational agents. DESIGN: This is a
prospective, observational study. PARTICIPANTS: Sixty-two subjects were enrolled.
Sixty (29 normal sighted and 31 visually impaired) were eligible; 54 (28 visually
impaired and 26 normal-sighted) completed all testing visits. METHODS: Subjects
navigated MLMT courses three times over 1 year. At each visit, subjects completed
testing using individual eyes, and both eyes, at up to nine standardized,
increasing luminance levels (range 1 to 400 lux). Accuracy and speed were
evaluated and compared with visual acuity (VA), visual field (VF) and a visual
function questionnaire. MAIN OUTCOME MEASURES: Accuracy and speed of normal and
visually impaired subjects on MLMT, and reliability and content validity of MLMT
were the main outcome measures. RESULTS: MLMT distinguished normal-sighted from
visually impaired subjects. All control subjects passed all MLMT attempts at all
tested light levels. Visually impaired subjects' performance varied widely; some
declined over 1 year. Performance declined markedly below certain VA and VF
thresholds. Concordance on performance on two baseline visits was high:
correlations for accuracy were 94% and 98% for lowest common and highest common
lux levels. CONCLUSIONS AND RELEVANCE: MLMT differentiated visually impaired from
control populations and, in visually impaired subjects, identified a range of
performances; and tracked performance declines over time, consistent with these
progressive conditions.
PMID- 28697538
TI - Overactive bladder is a negative predictor of achieving continence after robot
assisted radical prostatectomy.
AB - OBJECTIVES: To investigate predictors of continence outcomes after robot-assisted
radical prostatectomy. METHODS: Clinical records of 272 patients who underwent
robot-assisted radical prostatectomy were investigated. Preoperative Overactive
Bladder Symptom Score, International Prostate Symptom Score and
clinicopathological factors were investigated, and relationships between factors
and recovery of continence after robot-assisted radical prostatectomy were
assessed. The presence of overactive bladder was defined as having urgency for
more than once a week and having >=3 points according to the Overactive Bladder
Symptom Score. RESULTS: Age (<=66 years) was significantly associated with
continence within 6 months after robot-assisted radical prostatectomy (P =
0.033). The absence of overactive bladder and lower Overactive Bladder Symptom
Score (<3) were significantly associated with recovery of continence within 12
months after surgery (both variables P = 0.009). In terms of achieving recovery
of continence after robot-assisted radical prostatectomy, Kaplan-Meier curves
showed earlier recovery in "age <=66 years," "prostate weight <=40 g" and
"overactive bladder symptom score <3" (P = 0.0072, 0.0172 and 0.0140,
respectively). Multivariate analysis showed that the presence of overactive
bladder was an independent negative predictor for recovery of continence within
12 months after surgery (P = 0.019). CONCLUSIONS: The presence of baseline
overactive bladder seems to represent an independent negative predictor for
recovery of continence at 12 months after robot-assisted radical prostatectomy.
PMID- 28697539
TI - Anaemia in children: are we using the correct prevention strategies?
PMID- 28697540
TI - Three doses of oral misoprostol versus an intra-cervical Foley catheter for 24
hours for pre-induction cervical ripening in post- dated pregnancies: a
randomized controlled trial
AB - Objectives: To compare three doses of oral misoprostol 50MUg four hourly versus
an intra-cervical Foley catheter for 24 hours, for pre-induction cervical
ripening. Methods: Primary investigator blinded, randomised controlled trial
conducted in 180 consecutive women with singleton uncomplicated pregnancies with
Modified Bishop Score (MBS) ?5 at 40 weeks + 6 days gestation, allocated by
stratified (primigravida / multigravida) block randomization to receive three
doses of oral misoprostol 50MUg four hourly or an intra-cervical Foley catheter
for 24 hours. MBS reassessed at 41 weeks gestation. If MBS ?7, induction of
labour (IOL) with amniotomy and intravenous oxytocin infusion. If MBS<7, cross
over therapy with intracervical Foley catheter for misoprostol group, vaginal
prostaglandin E2 for Foley group. Results: At commencement, no significant
differences in age, parity, body mass index and MBS between the two groups.
Greater proportions established labour in both primigravidae (30% vs. 9%; RR=4.4,
95% CI 1.3-14.6; p=0.01) and multigravidae (44%.vs.16%; RR=4.3; 95% CI 1.6-11.8;
p=0.003) before 41 weeks of gestation in misoprostol group compared to the Foley
group. Among the multigravidae, the mean increase of MBS was greater in the
misoprostol group (3.1; 95% CI 2.4-4) compared to the Foley group (2.4; 95% CI
1.9-2.7, p=0.04). One primigravida and two multigravidae developed hyper
stimulation after misoprostol therapy. No significant differences in the other
maternal and perinatal outcomes. Conclusions: Compared to an intra-cervical Foley
catheter for 24 hours, three doses of oral misoprostol 50MUg four hourly was more
effective for cervical ripening and even resulted in IOL.
PMID- 28697541
TI - First experience of cadaveric renal transplantation in Sri Lanka
AB - Objectives: To analyse the outcome of 50 consecutive cadaveric renal transplants
performed in Sri Lanka. Methods: This was a single-centre longitudinal cohort
study conducted in the Nephrology and Kidney Transplant Unit, Teaching Hospital
Kandy, Sri Lanka. Records of 50 Sri Lankan cadaveric renal transplant recipients
from 7th December 2004 to 1st September 2013 were reviewed and categorized
according to early graft function, cold ischaemia time and the duration of
dialysis before surgery. Results: Out of the 50 patients, twenty one (42%) had
immediate graft function (IGF), 26 (52%) delayed graft function (DGF), and 2 (4%)
primary non function (PNF). The average cold ischaemia time (CIT) was 8.8 hours.
Out of 23 patients who died during the study period, 19 (82.6%) died although
they had a functioning graft. Infection was the commonest cause of death (n=15;
65.2%). Rejection occurred in four (17.4%). Patient survival was 77.3% at one
year, 63.0% at three years and46% at five years. Graft survival was 93.2% at one
year, 88.9% at 3 years and 84.6% at 5 years when death with a functioning graft
was censored. Univariate analysis revealed that neither CIT nor duration of
dialysis before transplant affected patient survival. There was no significant
difference in patient survival between DGF and IGF. Conclusions: The events
occurring in the early period following renal transplantation do not have a
significant impact on long term graft outcome or patient survival. Infection is
the commonest cause of death after renal transplantation and efforts should be
directed to understand and prevent this complication.
PMID- 28697542
TI - Ti3+ self-doped mesoporous black TiO2/graphene assemblies for unpredicted-high
solar-driven photocatalytic hydrogen evolution.
AB - Ti3+ self-doped mesoporous black TiO2/graphene assemblies are fabricated by a
facile solvothermal method and surface hydrogenation. The structure,
crystallinity, morphology, and chemical state of the as-prepared samples are
characterized in detail by X-ray diffraction, Raman, X-ray photoelectron
spectroscopy, transmission electron microscopy, N2 adsorption and UV-visible
diffuse reflectance spectroscopy. The results show that the presence of Ti3+ can
efficiently extend the photoresponse of anatase TiO2 to visible light region. The
solar-driven photocatalytic hydrogen evolution shows that Ti3+ self-doped
mesoporous black TiO2/graphene assemblies exhibit the highest photocatalytic
activity (186MUmolh-1 0.01g-1), exceeding to mesoporous TiO2/graphene assemblies
and mesoporous black TiO2. It also exhibits superior photoelectrochemical
properties compared with mesoporous TiO2/graphene assemblies. The unpredicted
high photocatalytic performance is attributed to the close contact between the
unique two-dimensional graphene structures coupled with TiO2 mesoporous
architectures resulting in outstanding charge separation efficient and the Ti3+
self-doping extending the utilization ratio of visible light.
PMID- 28697543
TI - Porous alpha-Fe2O3 microflowers: Synthesis, structure, and enhanced acetone
sensing performances.
AB - Porous alpha-Fe2O3 microflowers, which were composed of many nanospindles
assembled by large numbers of nanoparticles, were successfully synthesized by
calcining the FeSO4(OH) precursor prepared through a simple ethanol-mediated
method. Various techniques were employed to obtain the crystalline and
morphological properties of the as-prepared products. The formation process of
such microstructure was proposed according to the morphology and component of the
products obtained at different reaction time. Moreover, the obtained alpha-Fe2O3
was utilized as sensing materials upon exposure to various test gases. As
expected, in virtue of the less-agglomerated configuration and unique porous
structure, the hierarchical alpha-Fe2O3 microflowers exhibited higher response as
well as faster response/recovery time to acetone when compared with alpha-Fe2O3
nanoparticles. Significantly, the response time was measured to be 1s at the low
operating temperature of 210 degrees C.
PMID- 28697544
TI - Embedded vertically aligned cadmium telluride nanorod arrays grown by one-step
electrodeposition for enhanced energy conversion efficiency in three-dimensional
nanostructured solar cells.
AB - Vertically aligned CdTe nanorods (NRs) arrays are successfully grown by a simple
one-step and template-free electrodeposition method, and then embedded in the CdS
window layer to form a novel three-dimensional (3D) heterostructure on flexible
substrates. The parameters of electrodeposition such as deposition potential and
pH of the solution are varied to analyze their important role in the formation of
high quality CdTe NRs arrays. The photovoltaic conversion efficiency of the solar
cell based on the 3D heterojunction structure is studied in detail. In comparison
with the standard planar heterojunction solar cell, the 3D heterojunction solar
cell exhibits better photovoltaic performance, which can be attributed to its
enhanced optical absorption ability, increased heterojunction area and improved
charge carrier transport. The better photoelectric property of the 3D
heterojunction solar cell suggests great application potential in thin film solar
cells, and the simple electrodeposition process represents a promising technique
for large-scale fabrication of other nanostructured solar energy conversion
devices.
PMID- 28697545
TI - Synthesis of reduced-size gold nanostars and internalization in SH-SY5Y cells.
AB - The synthesis of large pentatwinned five-branched gold nanostars (GNS) has been
modified so to obtain overall dimensions shrunk to 60% and a lower branches
aspect ratio, leading to a dramatic blue shift of their two near-infrared (NIR)
localized surface plasmon resonances (LSPR) absorptions but still maintaining one
LSPR in the biotransparent NIR range. The interactions of polyethylene glycol
(PEG) coated large and shrunk GNS with SH-SY5Y cells revealed that the large ones
(DCI - diameter of the circumference in which GNS can be inscribed=76nm) are
internalized more efficiently than the shrunk ones (DCI=46nm), correlating with a
decreased cells surviving fraction.
PMID- 28697546
TI - Development of novel anionic Gemini surfactants and application in fabricating
hierarchical silver microparticles for surface-enhanced Raman spectroscopy.
AB - In this work, a new category of anionic Gemini surfactants with a rigid space,
disodium 2,2'-(1, 4-phenylene bis (methylene)) bis (alkane-1-sulfate) (CmArCm,
m=8, 10, 12, 14), were developed. They showed excellent surface activity and
remarkable micellization tendency in aqueous solutions as measured by the
equilibrium surface tension method. It was noticed that both the surface activity
and micellization ability of CmArCm were gradually strengthened upon increasing
the hydrophobic chain length m. Those Gemini surfactants were employed as capping
reagents to fabricate three-dimensional (3D) hierarchical silver microparticles
(AgMPs) successfully even in a large-scale of gram-level. The morphological
evolution of these microparticles in different conditions was investigated
systematically by various techniques including scanning electron microscopy
(SEM), high-resolution transmission electron microscope (HRTEM), powder X-ray
diffraction (XRD), and Fourier transform infrared spectroscopy (FTIR). The
possible formation mechanism of surfactant assisted AgMPs was also proposed. It
was found that the morphology of AgMPs could be tailored from nut-like, lichi
like, to coral-like microparticles by simply varying the concentration of
surfactant. However, the hydrophobic chain length m of CmArCm showed a little
influence on the morphology of AgMPs. Moreover, the surface-enhanced Raman
scattering of Rhodamine 6G results evidently confirmed the superior surface
activity of synthesized AgMPs.
PMID- 28697547
TI - Effect of surfactant concentration and solidification temperature on the
characteristics and stability of nanostructured lipid carrier (NLC) prepared from
rambutan (Nephelium lappaceum L.) kernel fat.
AB - Nanostructured lipid carrier (NLC) was fabricated from rambutan (Nephelium
lappaceum L.) kernel fat stabilized with Tween 80 in this present work. The
influence of the Tween 80 concentration (0.025, 0.05, 0.1, 0.2, 0.5 and 1.0wt%)
and solidification temperature (5 and 25 degrees C) on the characteristics and
stability of the NLC were investigated. The results showed that an increase in
the Tween 80 concentration caused decreased zeta-potential (zeta-potential) and
particle size (Z-average) with no significant effect on the polydispersity index
(PDI). Lipid particles in the NLC at all Tween 80 concentrations had a tendency
to grow and the PDI tended to increase due to Ostwald ripening upon storage over
28days. At least 0.2wt% Tween 80 concentrations could be used to stabilize 1wt%
rambutan NLC. The solidification temperature affected the microstructure, melting
behavior and stability of rambutan NLC. Pre-solidification at 5 degrees C could
create stable NLC with monodispersed-spherical lipid particles. Consequently,
these stable NLC particles produced from rambutan kernel fat may serve as useful
carriers for the delivery of bioactive lipophilic nutraceuticals.
PMID- 28697548
TI - Spectral induced polarization of Na-montmorillonite dispersions.
AB - Montmorillonite (Mt) clays have a high specific surface area and surface charge,
which confer them remarkable adsorption properties. Nevertheless, their
electrochemical and aggregation behavior are not completely elucidated because of
the complexity of their microstructural and interfacial properties. In this work,
the conductive and dispersive properties of Na-Mt suspensions of weight fractions
0.5-5.2% were investigated for the first time using the spectral induced
polarization method. A four-electrode system was used to reduce errors introduced
by electrode polarization and contact resistances. Complex conductivity spectra
in the low-frequency range of 0.1Hz to 45kHz were successfully described using a
triple layer model of the basal surface of Mt and a complex conductivity model
that considers conduction of the diffuse layer and polarization of the Stern
layer. Aggregate size distributions were inferred from inverted relaxation time
distributions. We found that the negative and permanent surface charge of the
basal plane of Na-Mt controls its quadrature (imaginary) conductivity, which is
not very sensitive to pH and salinity (NaCl) in the 100Hz to 45kHz frequency
range. For lower frequencies, the sudden increase of the quadrature conductivity
at the highest salinities was explained by considering coagulation of Na-Mt
particles.
PMID- 28697549
TI - Deamidation of pseudopeptidic molecular hydrogelators and its application to
controlled release.
AB - HYPOTHESIS: The incorporation of a succinic acid-derived moiety in amino acid
derivatives would favor an intramolecular catalysis of a deamidation reaction.
Such reaction would permit controlled disassembly of molecular hydrogelators and
the use of the hydrogels for controlled release of actives. EXPERIMENTAL: Low
molecular weight hydrogelators containing a succinic acid-derived moiety were
prepared by conventional organic synthesis procedures. Hydrogels were examined by
electron microscopy and 1HNMR studies were carried out to evaluate the solubility
in water of the hydrogelators and the deamidation reaction. Liberation of Rose
Bengal entrapped in the hydrogels was monitored by UV-Vis spectroscopy. FINDINGS:
Molecular hydrogels formed by pseudopeptidic derivatives of l-valine suffer a
thermal deamidation reaction, leading to partial disassembly. The succinic acid
derived moiety present in the gelators is responsible of intramolecular catalysis
of a deamidation reaction. Such neighboring group effect is reminiscent of
biochemical processes such as protein deamidation and self-excision of inteins.
It has been found that the thermodynamic equilibrium of the deamidation reaction
is regulated by the efficiency of hydrogelation. As a proof of concept, the
thermally promoted deamidation is applied to controlled release of Rose Bengal.
PMID- 28697550
TI - Capillary force on a tilted cylinder: Atomic Force Microscope (AFM) measurements.
AB - HYPOTHESIS: The capillary force in situations where the liquid meniscus is
asymmetric, such as the one around a tilted object, has been hitherto barely
investigated even though these situations are very common in practice. In
particular, the capillary force exerted on a tilted object may depend on the
dipping angle i. EXPERIMENTS: We investigate experimentally the capillary force
that applies on a tilted cylinder as a function of its dipping angle i, using a
home-built tilting Atomic Force Microscope (AFM) with custom made probes. A
micrometric-size rod is glued at the end of an AFM cantilever of known stiffness,
whose deflection is measured when the cylindrical probe is dipped in and
retracted from reference liquids. FINDINGS: We show that a torque correction is
necessary to understand the measured deflection. We give the explicit expression
of this correction as a function of the probes' geometrical parameters, so that
its magnitude can be readily evaluated. The results are compatible with a
vertical capillary force varying as 1/cosi, in agreement with a recent
theoretical prediction. Finally, we discuss the accuracy of the method for
measuring the surface tension times the cosine of the contact angle of the liquid
on the probe.
PMID- 28697551
TI - N-acyl-homoserine lactone dynamics during biofilm formation of a 1,2,4
trichlorobenzene mineralizing community on clay.
AB - In Gram-negative bacteria, quorum sensing systems are based on the N-acyl
homoserine lactone (AHL) molecule. The objective of this study was to investigate
the role of quorum sensing systems during biofilm formation by a microbial
community while degrading the pollutant. Our model system included 1,2,4
trichlorobenzene (1,2,4-TCB) and its mineralizing Gram-negative bacterial
community to investigate the relationships between AHL dynamics, cell growth and
pollutant degradation. Biomineralization of 1,2,4-TCB was monitored for both the
planktonic bacterial community with and without sterile clay particles in liquid
cultures. The bacterial growth and production of AHLs were quantified by
fluorescent in situ hybridization and immunoassay analysis, respectively. A rapid
production of AHLs which occurred coincided with the biofilm formation and the
increase of mineralization rate of 1,2,4-TCB in liquid cultures. There is a
positive correlation between the cell density of Bodertella on the clay particles
and mineralization rate of 1,2,4-TCB. 3-oxo-C12:1-HSL appears to be the dominant
AHL with the highest intensity and rapidly degraded by the bacterial community
via two main consecutive reactions (lactone hydrolysis and decarboxylic
reaction). These findings suggest that the integrated AHLs and their degraded
products play a crucial role in biofilm formation and biomineralization of 1,2,4
TCB in culture.
PMID- 28697552
TI - The importance of tattoo pigment in sentinel lymph nodes.
AB - BACKGROUND: The presence of pigment in axillary lymph nodes (LN) secondary to
migration of tattoo ink can imitate the appearance of a blue sentinel lymph node
(SLN) on visual inspection, causing the operator to either miss the true SLN or
excise more than is needed. OBJECTIVE: We present patients with tattoos
ipsilateral to an early stage breast cancer who underwent a SLN biopsy. METHODS:
Patients were retrospectively reviewed from medical records and clinicopathologic
data was collected. A total of 52 LNs were retrieved from 15 patients for
sentinel mapping and 29 of them had tattoo pigmentation on pathologic evaluation.
RESULTS: Of those 29 SLNs, 2 of them (6.9%) were pigmented, but did not contain
either blue dye or Tc-99m (pseudopigmented SLN). Two (3.8%) SLNs were positive
for metastasis; both of these had either blue dye or Tc99m uptake, and 1
demonstrated tattoo pigment in the node. CONCLUSIONS: In this cohort of patients
with ipsilateral tattoos, removed more LNs lead to unnecessary excision which may
important for increasing the risk of arm morbidity from SLN biopsy. However, the
presence of tattoo pigment did not interfere with understaging for axillary
mapping and it did not effect of pathological identification of SLNs positivity.
PMID- 28697553
TI - Impact of training volume and intensity on RBC-NOS/NO pathway and endurance
capacity.
AB - BACKGROUND: Acute exercise increases red blood cell-nitric oxide synthase (RBC
NOS) activation and RBC deformability but the effect of regular training remains
unclear. OBJECTIVE: To detect the chronic effect of enduring moderate and high
intensity training on the RBC-NOS/NO pathway and to detect a relation between RBC
deformability and endurance capacity. METHODS: 38 healthy male subjects were
randomly assigned to one of three training groups: High Volume Training (HVT; 120
140 beats per minute (bpm)), High Intensity Training (HIT; 160-180 bpm) and
Moderate Intensity Training (MIT; 140-160 bpm). Blood parameters, maximum oxygen
capacity (VO2 max), RBC deformability, RBC nitrite level and RBC-NOS activation
were measured after venous blood sampling at rest pre (T0) and after six weeks of
training (T1). RESULTS: RBC-NOS activation, RBC nitrite concentration and RBC
deformability were significantly increased at T1 in the HIT group. Parameters
were unaltered in MIT and HVT. Maximum oxygen uptake was only significantly
increased in the HIT group and regression analysis revealed positive regression
between VO2 max and RBC deformability. CONCLUSIONS: High intensity training was
the only training programme that sustainably affected RBC-NOS dependent NO
production and performance capacity. HIT therefore represents a time efficient
training program resulting in improved RBC function potentially improving
physical condition.
PMID- 28697554
TI - Egocentric versus Allocentric Spatial Memory in Behavioral Variant Frontotemporal
Dementia and Alzheimer's Disease.
AB - BACKGROUND: Diagnosis of behavioral variant frontotemporal dementia (bvFTD) can
be challenging, in particular when patients present with significant memory
problems, which can increase the chance of a misdiagnosis of Alzheimer's disease
(AD). Growing evidence suggests spatial orientation is a reliable cognitive
marker able to differentiate these two clinical syndromes. OBJECTIVE: Assess the
integrity of egocentric and allocentric heading orientation and memory in bvFTD
and AD, and their clinical implications. METHOD: A cohort of 22 patients with
dementia (11 bvFTD; 11 AD) and 14 healthy controls were assessed on the virtual
supermarket task of spatial orientation and a battery of standardized
neuropsychological measures of visual and verbal memory performance. RESULTS:
Judgements of egocentric and allocentric heading direction were differentially
impaired in bvFTD and AD, with AD performing significantly worse on egocentric
heading judgements than bvFTD. Both patient cohorts, however, showed similar
degree of impaired allocentric spatial representation, and associated hippocampal
pathology. CONCLUSIONS: The findings suggest egocentric heading judgements offer
a more sensitive discriminant of bvFTD and AD than allocentric map-based measures
of spatial memory.
PMID- 28697555
TI - Subjective Cognitive Complaints in Cognitively Healthy Older Adults and Their
Relationship to Cognitive Performance and Depressive Symptoms.
AB - BACKGROUND: Subjective cognitive complaints (SCCs) may be an early marker of
prodromal Alzheimer's disease. OBJECTIVES: Using a 10-item yes/no SCCs
questionnaire (Le Questionnaire de Plainte Cognitive [QPC]), we evaluated the
prevalence and distribution of SCCs in cognitively healthy Czech older adults and
examined total score and specific QPC items in relation to depressive
symptomology and cognitive performance. METHODS: A sample of 340 cognitively
healthy older community-dwelling volunteers aged 60 or older from the third wave
of the longitudinal project National Normative Study of Cognitive Determinants of
Healthy Aging, who underwent a comprehensive neuropsychological assessment and
completed the QPC and the 15-item Geriatric Depression Scale (GDS-15). Regression
analysis was controlled for age when GDS-15 was the outcome and for age and GDS
15 with cognitive domains as the outcome. RESULTS: 71% reported 1 + SCCs, with
prevalence of individual complaints ranging from 4% to 40%. The number of SCCs
was associated with GDS-15 (p < 0.001). Personality change (p < 0.001) and
Limitation in daily activities (p = 0.002) were significantly associated with
higher GDS-15 score and Spatial orientation difficulties (p = 0.019) and
Impression of worse memory in comparison to peers (p = 0.012) were significantly
associated with lower memory performance. CONCLUSIONS: We identified some
cognitive complaints that were very common in our sample. Overall, a higher
number of SCCs in well cognitively functioning individuals was most closely
related to depressive symptomatology, while some specific complaints reflected
lower memory performance and should be considered when screening for people at
risk of cognitive decline.
PMID- 28697556
TI - proBDNF Accelerates Brain Amyloid-beta Deposition and Learning and Memory
Impairment in APPswePS1dE9 Transgenic Mice.
AB - BACKGROUND: Alzheimer's disease (AD) is pathologically known for the amyloid-beta
(Abeta) deposition, neurofibrillary tangles, and neuronal loss in the brain. The
precursor of brain-derived neurotrophic factor (proBDNF) before proteolysis has
opposing functions to its mature form in neuronal survival and neurite growth.
However, the role of proBDNF in the pathogenesis of AD remains unclear.
OBJECTIVE: To investigate the effects of proBDNF on neurons in vitro, and on
learning and memory impairment and brain Abeta production in a transgenic AD
mouse model (APPswePS1dE9). METHODS: We here examined the effects of proBDNF on
the viability (MTT assay) and neurite growth (morphologic measurement) of the
primary neurons in vitro. After the intracerebroventricular injection of adeno
associated virus-proBDNF (AAV-proBDNF), we then investigated the learning and
memory impairment (Morris water maze) and Abeta deposition in the brains of the
AD mice. RESULTS: The results showed that proBDNF could inhibit neuronal
viability and neurite growth in vitro, enhance Abeta levels, and accelerate its
deposition in the brain, which was consistent with the learning and memory
impairment of AD mice, likely dependent on the membrane receptor of p75NTR.
CONCLUSIONS: Our findings suggest that proBDNF may exert a crucially negative
effect during AD pathogenesis andprogression.
PMID- 28697557
TI - Comparison of Different Hypotheses Regarding the Spread of Alzheimer's Disease
Using Markov Random Fields and Multimodal Imaging.
AB - Alzheimer's disease (AD) is characterized by a cascade of pathological processes
that can be assessed in vivo using different neuroimaging methods. Recent
research suggests a systematic sequence of pathogenic events on a global
biomarker level, but little is known about the associations and dependencies of
distinct lesion patterns on a regional level. Markov random fields are a
probabilistic graphical modeling approach that represent the interaction between
individual random variables by an undirected graph. We propose the novel
application of this approach to study the interregional associations and
dependencies between multimodal imaging markers of AD pathology and to compare
different hypotheses regarding the spread of the disease. We retrieved multimodal
imaging data from 577 subjects enrolled in the Alzheimer's Disease Neuroimaging
Initiative. Mean amyloid load (AV45-PET), glucose metabolism (FDG-PET), and gray
matter volume (MRI) were calculated for the six principle nodes of the default
mode network- a functional network of brain regions that appears to be
preferentially targeted by AD. Multimodal Markov random field models were
developed for three different hypotheses regarding the spread of the disease: the
"intraregional evolution model", the "trans-neuronal spread" hypothesis, and the
"wear-and-tear" hypothesis. The model likelihood to reflect the given data was
evaluated using tenfold cross-validation with 1,000 repetitions. The most likely
graph structure contained the posterior cingulate cortex as main hub region with
edges to various other regions, in accordance with the "wear-and-tear" hypothesis
of disease vulnerability. Probabilistic graphical models facilitate the analysis
of interactions between several variables in a network model and therefore afford
great potential to complement traditional multiple regression analyses in
multimodal neuroimaging research.
PMID- 28697558
TI - Comparative Analysis of Cortical Microinfarcts and Microbleeds using 3.0-Tesla
Postmortem Magnetic Resonance Images and Histopathology.
AB - Microvascular lesions including cortical microinfarctions (CMIs) and cerebral
lobar microbleeds (CMBs) are usually caused by cerebral amyloid angiopathy (CAA)
in the elderly and are correlated with cognitive decline. However, their
radiological-histopathological coincidence has not been revealed systematically
with widely used 3-Tesla (3T) magnetic resonance imaging (MRI). The purpose of
the present study is to delineate the histopathological background corresponding
to MR images of these lesions. We examined formalin-fixed 10-mm thick coronal
brain blocks from 10 CAA patients (five were also diagnosed with Alzheimer's
disease, three with dementia with Lewy bodies, and two with CAA only) with
dementia and six non CAA patients with neurodegenerative disease. Using 3T MRI,
both 3D-fluid attenuated inversion recovery (FLAIR) and 3D-double inversion
recovery (DIR) were examined to identify CMIs, and T2* and susceptibility
weighted images (SWI) were examined to identify CMBs. These blocks were
subsequently examined histologically and immunohistochemically. In CAA patients,
48 CMIs and 6 lobar CMBs were invariably observed in close proximity to
degenerated Abeta-positive blood vessels. Moreover, 16 CMIs (33%) of 48 were
detected with postmortem MRI, but none were seen when the lesion size was smaller
than 1 mm. In contrast, only 1 undeniable CMI was founded with MRI and
histopathology in 6 non CAA patients. Small, cortical high-intensity lesions seen
on 3D-FLAIR and 3D-DIR images likely represent CMIs, and low-intensity lesions in
T2* and SWI correspond to CMBs with in vivo MRI. Furthermore, a close association
between amyloid-laden vessels and these microvascular lesions indicated the
contribution of CAA to their pathogenesis.
PMID- 28697560
TI - Relationship Between Body Mass Index, ApoE4 Status, and PET-Based Amyloid and
Neurodegeneration Markers in Amyloid-Positive Subjects with Normal Cognition or
Mild Cognitive Impairment.
AB - Body weight loss in late-life is known to occur at a very early stage of
Alzheimer's disease (AD). Apolipoprotein E4 (ApoE4) represents a major genetic
risk factor for AD and is linked to an increased cortical amyloid-beta (Abeta)
accumulation. Since the relationship between body weight, ApoE4, and AD pathology
is poorly investigated, we aimed to evaluate whether ApoE4 allelic status
modifies the association of body mass index (BMI) with markers of AD pathology. A
total of 368 Abeta-positive cognitively healthy or mild cognitive impaired
subjects had undergone [18F]-AV45-PET, [18F]-FDG-PET, and T1w-MRI examinations.
Composite cortical [18F]-AV45 uptake and [18F]-FDG uptake in posterior cingulate
cortex were calculated as surrogates of cortical Abeta load and glucose
metabolism, respectively. Multiple linear regressions were performed to assess
the relationships between these PET biomarkers with BMI, present cognitive
performance, and cognitive changes over time. Multivariate analysis of covariance
was conducted to test for statistical differences between ApoE4/BMI categories on
the PET markers and cognitive scores. In carriers of the ApoE4 allele only, BMI
was inversely associated with cortical amlyoid load (beta= -0.193, p < 0.005) and
recent cognitive decline (beta= -0.209, p < 0.05), and positively associated with
cortical glucose metabolism in an AD-vulnerable region (beta= 0.145, p < 0.05).
ApoE4/BMI category analyses demonstrated lower Abeta load, higher posterior
cingulate glucose metabolism, improved cognitive performance, and lower
progression of cognitive decline in obese ApoE4 carriers. The effect of ApoE4 in
promoting the accumulation of cortical amyoid, which may itself be a driver for
weight loss, may be moderated by altering leptin signaling in the hypothalamus.
PMID- 28697559
TI - Depressive Symptoms and Tau Accumulation in the Inferior Temporal Lobe and
Entorhinal Cortex in Cognitively Normal Older Adults: A Pilot Study.
AB - BACKGROUND: Depressive symptoms are common in older adults and associated with
increased morbidity and cognitive decline. These symptoms occur during
preclinical and prodromal stages of Alzheimer's disease (AD), but their
relationship to tau, one of the main AD proteinopathies, is poorly understood.
OBJECTIVE: The objective of this study was to investigate the cross-sectional
association between depressive symptoms and cerebral tau [18F T807 (also known as
18F-AV-1451) tau positron emission tomography (PET) imaging] in cognitively
normal (CN) older adults. METHODS: We measured depressive symptoms using the
Geriatric Depression Scale (GDS), and in vivo cerebral tau using T807 PET in 111
CN older adults. We employed general linear regression models to evaluate the
relationship of GDS score regressed on entorhinal cortex (EC) or inferior
temporal (IT) tau in separate backward elimination models. Other predictors
included age, sex, and in secondary analyses, amyloid (Pittsburgh Compound B
PET). RESULTS: Higher GDS was significantly associated with greater IT tau
(partial r = 0.188, p = 0.050) and marginally associated with greater EC tau
(partial r = 0.183, p = 0.055). In additional analyses including both linear and
quadratic age terms, we found a significant U-shaped relation of GDS to age (p =
0.001). CONCLUSIONS: Results suggest that IT and EC tau are modestly associated
with depressive symptoms in CN older adults. Findings suggest a link between
depressive symptoms and tau-mediated neurodegeneration in a region vulnerable in
AD. Future longitudinal studies examining the association of more severe
depressive symptoms and cerebral tau accumulation are needed to substantiate this
finding and to guide prevention and treatment in AD.
PMID- 28697561
TI - Specific Verbal Memory Measures May Distinguish Alzheimer's Disease from Dementia
with Lewy Bodies.
AB - BACKGROUND: Standard measures of commonly used memory tests may not be
appropriate to distinguish different neurodegenerative diseases affecting memory.
OBJECTIVE: To study whether specific measures of verbal memory obtained with the
Rey Auditory Verbal Learning test (RAVLT) could help distinguish dementia with
Lewy bodies (DLB) from Alzheimer's disease (AD). METHODS: Twenty-nine DLB and 32
AD patients participated in the study and were followed longitudinally for 3
years until the diagnosis was confirmed according to standard clinical criteria.
Twenty-eight healthy elderly subjects served as controls. The following verbal
memory measures were evaluated: verbal learning (VL), verbal forgetting (VF),
percentage of verbal forgetting (VF%), and serial position effects of the
immediate recall performance. RESULTS: DLB and AD groups have comparable
performances at the RAVLT immediate and delayed recall tasks. However, VL was
higher in DLB than AD while VF% was greater in AD. With a VF% cut-off >=75%, AD
and DLB patients were differently distributed, with 58% of AD versus 21% of DLB
above this cut-off. The recency effect was significant higher in AD than DLB.
DISCUSSION: DLB patients had a better performance in VL than AD, but worse VF and
recency effect. These specific measures of verbal memory could be used as
cognitive markers in the differential diagnosis between these two conditions.
PMID- 28697562
TI - The Montreal Cognitive Assessment: Normative Data from a Large Swedish Population
Based Cohort.
AB - BACKGROUND: The Montreal Cognitive Assessment (MoCA) has a high sensitivity for
detecting cognitive dysfunction. Swedish normative data does not exist and
international norms are often derived from populations where cognitive impairment
has not been screened for and not been thoroughly assessed to exclude subjects
with dementia or mild cognitive impairment. OBJECTIVE: To establish norms for
MoCA and develop a regression-based norm calculator based on a large, well
examined cohort. METHODS: MoCA was administered on 860 randomly selected elderly
people from a population-based cohort from the EPIC study. Cognitive dysfunction
was screened for and further assessed at a memory clinic. After excluding
cognitively impaired participants, normative data was derived from 758 people,
aged 65-85. RESULTS: MoCA cut-offs (-1 to -2 standard deviations) for cognitive
impairment ranged from <25 to <21 for the lowest educated and <26 to <24 for the
highest educated, depending on age group. Significant predictors for MoCA score
were age, sex and level of education. CONCLUSION: We present detailed normative
MoCA data and cut-offs according to the DSM-5 criteria for cognitive impairment
based on a large population-based cohort of elderly individuals, screened and
thoroughly investigated to rule out cognitive impairment. Level of education,
sex, and age should be taken in account when evaluating MoCA score, which is
facilitated by our online regression-based calculator that provide percentile and
z-score for a subject's MoCA score.
PMID- 28697563
TI - Autonomic Cardiac Function in Preclinical Alzheimer's Disease.
AB - To explore early autonomic cardiac changes in pre-clinical Alzheimer's disease
(AD), we have evaluated electrocardiologic measures of vagal tone for 63 adults
(ages 55-75) at rest, during cognitive testing, and then again at rest. All
subjects had multiple risk factors for AD, and all completed amyloid PET scans
(18F-Florbetapir) to determine amyloid positivity (Abeta+). No change in
electrocardiographic measures were observed for Abeta+ participants under each
testing condition, whereas Abeta-subjects showed an expected increase in vagal
tone during the cognitive stress condition. These findings suggest an early
relationship between cortical Abeta accumulation, a precursor to AD development,
and autonomic cardiac function.
PMID- 28697564
TI - An Intracellular Amyloid-beta/AbetaPP Epitope Correlates with Neurodegeneration
in those Neuronal Populations Early Involved in Alzheimer's Disease.
AB - The main histopathological hallmarks of Alzheimer's disease (AD) are the
extracellular deposition of neuritic amyloid plaques, composed of amyloid-beta
(Abeta) peptide, and the intracellular accumulation of neurofibrillary tangles,
composed of hyperphosphorylated tau. Both traits are emulated in the 3xTg-AD
mouse model. Because the relevance of this model in the bibliography and the main
role of Abeta in neuronal impairment, here we have detailed the brain
Abeta/AbetaPP distribution to subsequently quantify cellular density and
intracellular burden for specific neuronal populations in the early stages of the
disease. 6E10 immunoreactivity was evident in the deep layers of the cerebral
cortex, in the pyramidal cell layer of the hippocampus, in the basolateral
amygdala nucleus, and in the deep cerebellar nuclei macroneurons; whereas the
specific neuronal populations with decreased cellular density were the large
pyramidal neurons from the layers V-VI in the cerebral cortex, the pyramidal
neurons from the CA2-3 region in the hippocampus, and the large neurons from the
basolateral nucleus in the amygdala, apart from the already reported deep
cerebellar nuclei. Interestingly, we found a strong correlation between
intracellular Abeta/AbetaPP burden and cellular density in all these populations.
In addition, behavioral testing showed the functional consequences of such a
neuronal depletion. Concretely, anxious-like behavior is manifested in the corner
and open-field tests, as well as cognitive functions shown to be impaired in the
novel object recognition test and Morris water maze paradigm. To our knowledge,
this is the first deep characterization of the specific neuronal populations
affected in the 3xTg-AD mouse model.
PMID- 28697565
TI - The Relationship between Markers of Inflammation and Degeneration in the Central
Nervous System and the Blood-Brain Barrier Impairment in Alzheimer's Disease.
AB - BACKGROUND: It is known that YKL-40- a marker of glial inflammation, and VILIP-1-
a marker of neuronal injury, reflect functional and structural changes in AD
brains, although there is limited data concerning their potential influence on
blood-brain barrier (BBB) homeostasis. OBJECTIVE: Therefore, the aim of our study
was to investigate the relationship between markers of inflammation and
degeneration in the central nervous system (CNS) of patients with AD and mild
cognitive impairment (MCI) as well as immunological response in CNS and BBB
function. METHODS: Cerebrospinal fluid (CSF) concentrations of proteins tested
were determined in 45 AD patients, 18 MCI subjects, and 23 non-demented controls
using ELISA method. RESULTS: CSF concentrations of YKL-40 were significantly
higher in MCI and AD patients, whereas CSF levels of VILIP-1 were statistically
higher in the AD group as compared to the subjects without cognitive deficits.
Elevated concentrations of YKL-40 correlated significantly with increased albumin
quotient and decreased Abeta42/40 ratio in AD patients and with IgG quotient in
the total study group. We did not find a relationship between VILIP-1 and
immunological parameters reflecting BBB dysfunction and humoral immune response.
CONCLUSION: Our findings indicate that YKL-40 may contribute to decreased
stability and increased permeability of BBB in AD patients. It is assumed that
YKL-40 is implicated in the development of brain barriers, although its precise
mechanism of action in the BBB disruption remains unrevealed. Further studies on
larger groups of patients are required to confirm our hypothesis.
PMID- 28697566
TI - Reduced Cerebrospinal Fluid Concentration of Apolipoprotein A-I in Patients with
Alzheimer's Disease.
AB - BACKGROUND: Apolipoprotein E (ApoE) has been extensively studied in Alzheimer's
disease (AD), but little is known of apolipoprotein A-I (ApoA-I) in cerebrospinal
fluid (CSF). OBJECTIVE: Plasma lipids as well as ApoA-I and ApoE in plasma and
CSF were determined and related to Mini-Mental State Examination (MMSE) score,
APOE genotype, and CSF AD biomarkers. METHODS: Consecutive patients with AD (n =
29), stable mild cognitive impairment (n = 13), other dementias (n = 14), and
healthy controls (n = 18) were included at a single center. RESULTS: AD patients
had higher plasma triglycerides and lower CSF ApoA-I concentration than controls
(both p < 0.05). CSF ApoE concentration was reduced in other dementias (p <
0.01). In AD as well as other dementias, the ratios between CSF and plasma
concentrations of both ApoA-I and ApoE were lower than those in the controls.
ApoA-I and ApoE in plasma and CSF were not influenced by APOEE4 allele
distribution. In the total study population (n = 74), CSF ApoA-I correlated
positively with MMSE score (r = 0.26, p < 0.05) and negatively with CSF P-tau (r
= -0.25, p < 0.05). CSF ApoE correlated positively with CSF concentrations of T
tau and P-tau in the total study population and in AD patients. CONCLUSION: CSF
ApoA-I was reduced in AD patients and associated with measures of cognitive
function and AD disease status. The mechanisms underlying the decreased
CSF:plasma ratios of ApoA-I and ApoE in AD and other dementias need to be
explored in further studies.
PMID- 28697567
TI - Antibodies to Signaling Molecules and Receptors in Alzheimer's Disease are
Associated with Psychomotor Slowing, Depression, and Poor Visuospatial Function.
AB - BACKGROUND: Alzheimer's disease (AD) is associated with several antibodies as
well as signaling molecules and receptors. These may be detrimental in the
presence of a disrupted blood-brain barrier (BBB). OBJECTIVE: To investigate
whether the levels of antibodies toward 33 signaling molecules involved in
neurotransmitter, vascular, and immune functions were associated with AD and,
within the AD group; cognitive function and mood. METHODS: Antibodies in sera
from patients with mild AD [(n = 91) defined as a Mini-Mental State Examination
>= 20 or a Clinical Dementia Rating Scale<=1] and healthy controls (n = 102) were
measured with enzyme-linked immunosorbent assays. Levels in AD and controls were
compared by Mann-Whitney test. In the AD group, associations between antibodies
and psychometric test scores were analyzed by robust regression. The false
discovery threshold was set to 0.05. RESULTS: Antibodies to serotonin receptors
[5-HT2AR (effect size (r) = 0.21, p = 0.004), 5-HT2CR (r = 0.25, p = 0.0005) and
5-HT7R (r = 0.21, p = 0.003)], vascular endothelial growth factor receptor 1
[VEGFR1 (r = 0.29, p < 0.001)] and immune-receptors (Stabilin-1 (r = 0.23, p =
0.001) and C5aR1 (r = 0.21, p = 0.004) were higher in AD. Psychomotor speed was
associated with D1R-abs (beta 0.49, p < 0.001), depression with ETAR-abs (beta
0.31, p < 0.001), and visuospatial function with 5-HT1AR-abs (beta 0.27, p =
0.004) despite similar antibody levels compared to controls. CONCLUSIONS:
Antibody levels to VEGFR1, serotonergic receptors, and receptors in the immune
system were increased in AD. Antibodies at similar levels as in controls were
associated cognitive dysfunction and depression in AD.
PMID- 28697568
TI - Autophagy-ERK1/2-Involved Disinhibition of Hippocampal Neurons Contributes to the
Pre-Synaptic Toxicity Induced by Abeta42 Exposure.
AB - Alzheimer's disease (AD) is a progressive neurodegenerative disease and the most
frequent cause of progressive cognitive decline in the elderly population. To
date, there is still no effective treatment for AD, requiring more underlying
mechanisms. In the present study, we investigated the effects of Abeta42 on the
inhibitory synaptic transmission in the cultured hippocampal neurons, and
explored the possible mechanism. The frequency, but not amplitude, of miniature
inhibitory post-synaptic currents was significantly suppressed by Abeta42,
indicating that Abeta42 played its role in inhibitory transmitter release at the
pre-synaptic sites. Abeta42 had no effect on miniature excitatory post-synaptic
currents, suggesting GABAergic synapses are more susceptible to Abeta42 exposure.
However, the number of GABAergic neurons or synapses was not influenced,
suggesting the corresponding stage may be a preclinical one. The effect of
Abeta42 can be mimicked by PD98059 (an inhibitor of ERK1/2) and blocked by
curcumin (an activator of MEK), which reveals Abeta-involved influence is via the
decreased phosphorylation of MAPK-ERK1/2. In addition, synaptophysin is confirmed
to be a downstream protein of MAPK-ERK1/2 at the pre-synaptic site. At the same
time, suppressed autophagy was observed after Abeta42 exposure, and the
activation of autophagy increased pERK1/2 level and salvaged the disinhibition of
hippocampal neurons. These data suggest that diminished GABAergic tone likely
starts from the preclinical stage of AD, so some GABAergic stress test may be
effective for identifying cognitively normal elder adults. Strategies against the
dysfunction of autophagy should be adopted in the early stage of AD because of
its initial effects.
PMID- 28697569
TI - Relationships of Dietary Patterns, Foods, and Micro- and Macronutrients with
Alzheimer's Disease and Late-Life Cognitive Disorders: A Systematic Review.
AB - In the last decade, the association between diet and cognitive function or
dementia has been largely investigated. In the present article, we systematically
reviewed observational studies published in the last three years (2014-2016) on
the relationship among dietary factors and late-life cognitive disorders at
different levels of investigation (i.e., dietary patterns, foods and food-groups,
and dietary micro- and macronutrients), and possible underlying mechanisms of the
proposed associations. From the reviewed evidence, the National Institute on
Aging-Alzheimer's Association guidelines for Alzheimer's disease (AD) and
cognitive decline due to AD pathology introduced some evidence suggesting a
direct relation between diet and changes in the brain structure and activity.
There was also accumulating evidence that combinations of foods and nutrients
into certain patterns may act synergistically to provide stronger health effects
than those conferred by their individual dietary components. In particular,
higher adherence to a Mediterranean-type diet was associated with decreased
cognitive decline. Moreover, also other emerging healthy dietary patterns such as
the Dietary Approach to Stop Hypertension (DASH) and the Mediterranean-DASH diet
Intervention for Neurodegenerative Delay (MIND) diets were associated with slower
rates of cognitive decline and significant reduction of AD rate. Furthermore,
some foods or food groups traditionally considered harmful such as eggs and red
meat have been partially rehabilitated, while there is still a negative
correlation of cognitive functions with saturated fatty acids and a protective
effect against cognitive decline of elevated fish consumption, high intake of
monounsaturated fatty acids and polyunsaturated fatty acids (PUFA), particularly
n-3 PUFA.
PMID- 28697570
TI - Adherence to Clinical Practice Guidelines during Dementia Work-Up in a Real-World
Setting: A Study from the Registry of Dementias of Girona.
AB - BACKGROUND: There are several position statements and clinical practice
guidelines (CPG) for diagnosing dementia. OBJECTIVE: Our aims were to evaluate
the adherence to CPG among specialists in the 7 memory clinics included in the
Registry of Dementias of Girona (ReDeGi), and to compare the results between 2007
2011 and 2012-2015. We also determined the time and number of visits required to
achieve a diagnosis, the supplementary tests ordered, and the drugs prescribed
according to dementia subtypes. METHODS: Medical charts of a stratified random
sample of 475 ReDeGi cases were reviewed. Basic dementia work-up was evaluated
using as a reference evidence-based CPG. An Index of Adherence (AI) was
calculated using the following items in the medical chart: cognitive
symptomatology; functional disability evaluation; physical examination;
neurological examination; psychiatric examination; brief cognitive examination;
activities of daily living performance examination; blood test; structural
neuroimaging (CT-scan or MRI). RESULTS: The mean AI to CPG among specialists was
of 8.2 points, and it improved from 7.9 points in 2007-2011 to 8.5 points in 2012
2015 (Cohen's d = 0.46). A lower adherence was detected in the most severe cases.
A dementia diagnosis required 3.5 visits, regardless of the subtype of dementia,
although milder cases required more time, more visits, and more supplementary
tests than severe cases. CONCLUSION: The adherence to CPG in the catchment area
of the ReDeGi is high, and an epidemiological surveillance system such as the
ReDeGi may help in improving it. Dementia guidelines should establish procedures
adapted to clinical practice, with simplified recommendations for most severe
cases.
PMID- 28697571
TI - PSD-93 Attenuates Amyloid-beta-Mediated Cognitive Dysfunction by Promoting the
Catabolism of Amyloid-beta.
AB - Amyloid-beta (Abeta) is a key neuropathological hallmark of Alzheimer's disease
(AD). Postsynaptic density protein 93 (PSD-93) is a key scaffolding protein
enriched at postsynaptic sites. The aim of the present study was to examine
whether PSD-93 overexpression could alleviate Abeta-induced cognitive dysfunction
in APPswe/PS1dE9 (APP/PS1) mice by reducing Abeta levels in the brain. The level
of PSD-93 was significantly decreased in the hippocampus of 6-month-old APP/PS1
mice compared with that in wild-type mice. Following lentivirus-mediated PSD-93
overexpression, cognitive function, synaptic function, and amyloid burden were
investigated. The open field test, Morris water maze test, and fear condition
test revealed that PSD-93 overexpression ameliorated spatial memory deficits in
APP/PS1 mice. The facilitation of long-term potentiation induction was observed
in APP/PS1 mice after PSD-93 overexpression. The expression of somatostatin
receptor 4 (SSTR4) and neprilysin was increased, while the amyloid plaque load
and Abeta levels were decreased in the brains of APP/PS1 mice. Moreover, PSD-93
interacted with SSTR4 and affected the level of SSTR4 on cell membrane, which was
associated with the ubiquitination. Together, these findings suggest that PSD-93
attenuates spatial memory deficits and decreases amyloid levels in APP/PS1 mice,
which might be associated with Abeta catabolism, and overexpression of PSD-93
might be a potential therapy for AD.
PMID- 28697572
TI - Delayed Recall and Working Memory MMSE Domains Predict Delirium following Cardiac
Surgery.
AB - BACKGROUND: Reduced preoperative cognition is a risk factor for postoperative
delirium. The significance for type of preoperative cognitive deficit, however,
has yet to be explored and could provide important insights into mechanisms and
prediction of delirium. OBJECTIVE: Our goal was to determine if certain cognitive
domains from the general cognitive screener, the Mini-Mental State Exam (MMSE),
predict delirium after cardiac surgery. METHODS: Patients completed a
preoperative MMSE prior to undergoing elective cardiac surgery. Following
surgery, delirium was assessed throughout ICU stay using the Confusion Assessment
Method for ICU delirium and the Richmond Agitation and Sedation Scale. RESULTS:
Cardiac surgery patients who developed delirium (n = 137) had lower total MMSE
scores than patients who did not develop delirium (n = 457). In particular,
orientation to place, working memory, delayed recall, and language domain scores
were lower. Of these, only the working memory and delayed recall domains
predicted delirium in a regression model adjusting for history of chronic
obstructive pulmonary disease, age, sex, and duration of cardiopulmonary bypass.
For each word not recalled on the three-word delayed recall assessment, the odds
of delirium increased by 50%. For each item missed on the working memory index,
the odds of delirium increased by 36%. Of the patients who developed delirium,
47% had a primary impairment in memory, 21% in working memory, and 33% in both
domains. The area under the receiver operating characteristics curve using only
the working memory and delayed recall domains was 0.75, compared to 0.76 for
total MMSE score. CONCLUSION: Delirium risk is greater for individuals with
reduced MMSE scores on the delayed recall and working memory domains. Research
should address why patients with memory and executive vulnerabilities are more
prone to postoperative delirium than those with other cognitive limitations.
PMID- 28697573
TI - Dual tasking negatively impacts obstacle avoidance abilities in post-stroke
individuals with visuospatial neglect: Task complexity matters!
AB - BACKGROUND: Persons with perceptual-attentional deficits due to visuospatial
neglect (VSN) after a stroke are at a risk of collisions while walking in the
presence of moving obstacles. The attentional burden of performing a dual-task
may further compromise their obstacle avoidance performance, putting them at a
greater risk of collisions. OBJECTIVE: The objective of this study was to compare
the ability of persons with (VSN+) and without VSN (VSN-) to dual task while
negotiating moving obstacles. METHODS: Twenty-six stroke survivors (13 VSN+, 13
VSN-) were assessed on their ability to (a) negotiate moving obstacles while
walking (locomotor single task); (b) perform a pitch-discrimination task
(cognitive single task) and (c) simultaneously perform the walking and cognitive
tasks (dual task). We compared the groups on locomotor (collision rates, minimum
distance from obstacle and onset of strategies) and cognitive (error rates)
outcomes. RESULTS: For both single and dual task walking, VSN+ individuals showed
higher collision rates compared to VSN- individuals. Dual tasking caused
deterioration of locomotor (more collisions, delayed onset and smaller minimum
distances) and cognitive performances (higher error rate) in VSN+ individuals.
Contrastingly, VSN- individuals maintained collision rates, increased minimum
distance, but showed more cognitive errors, prioritizing their locomotor
performance. CONCLUSION: Individuals with VSN demonstrate cognitive-locomotor
interference under dual task conditions, which could severely compromise safety
when ambulating in community environments and may explain the poor recovery of
independent community ambulation in these individuals.
PMID- 28697574
TI - tDCS does not enhance the effects of robot-assisted gait training in patients
with subacute stroke.
AB - BACKGROUND: Transcranial direct current stimulation (tDCS) is a non-invasive
brain stimulation technique, which can modulate cortical excitability and
combined with rehabilitation therapies may improve motor recovery after stroke.
OBJECTIVE: Our aim was to study the feasibility of a 4-week robotic gait training
protocol combined with tDCS, and to study tDCS to the leg versus hand motor
cortex or sham to improve walking ability in patients after a subacute stroke.
METHODS: Forty-nine subacute stroke patients underwent 20 daily sessions (5 days
a week for 4 weeks) of robotic gait training combined with tDCS. Patients were
assigned either to the tDCSleg group (n = 9), receiving 2 mA anodal tDCS over the
motor cortex leg representation (vertex), or an active control group (n = 17)
receiving anodal tDCS over the hand motor cortex area (tDCShand). In addition, we
studied 23 matched patients in a control group receiving gait training without
tDCS (notDCS). Study outcomes included gait speed (10-meter walking test), and
quality of gait, using the Functional Ambulatory Category (FAC) before and after
the 4-week training period. RESULTS: Only one patient did not complete the
treatment because he presented a minor side-effect. Patients in all three groups
showed a significantly improvement in gait speed and FAC. The tDCSleg group did
not perform better than the tDCShand or notDCS group. CONCLUSION: Combined tDCS
and robotic training is a safe and feasible procedure in subacute stroke
patients. However, adding tDCS to robot-assisted gait training shows no benefit
over robotic gait training alone.
PMID- 28697575
TI - Bimanual coordination: A missing piece of arm rehabilitation after stroke.
AB - Inability to use the arm in daily actions significantly lowers quality of life
after stroke. Most contemporary post-stroke arm rehabilitation strategies that
aspire to re-engage the weaker arm in functional activities have been greatly
limited in their effectiveness. Most actions of daily life engage the two arms in
a highly coordinated manner. In contrast, most rehabilitation approaches
predominantly focus on restitution of the impairments and unilateral practice of
the weaker hand alone. We present a perspective that this misalignment between
real world requirements and intervention strategies may limit the transfer of
unimanual capability to spontaneous arm use and functional recovery. We propose
that if improving spontaneous engagement and use of the weaker arm in real life
is the goal, arm rehabilitation research and treatment need to address the
coordinated interaction between arms in targeted theory-guided interventions.
Current narrow focus on unimanual deficits alone, difficulty in quantifying
bimanual coordination in real-world actions and limited theory-guided focus on
control and remediation of different coordination modes are some of the biggest
obstacles to successful implementation of effective interventions to improve
bimanual coordination in the real world. We present a theory-guided taxonomy of
bimanual actions that will facilitate quantification of coordination for
different real-world tasks and provide treatment targets for addressing
coordination deficits. We then present evidence in the literature that points to
bimanual coordination deficits in stroke survivors and demonstrate how current
rehabilitation approaches are limited in their impact on bimanual coordination.
Importantly, we suggest theory-based areas of future investigation that may
assist quantification, identification of neural mechanisms and scientifically
based training/remediation approaches for bimanual coordination deficits post
stroke. Advancing the science and practice of arm rehabilitation to incorporate
bimanual coordination will lead to a more complete functional recovery of the
weaker arm, thus improving the effectiveness of rehabilitation interventions and
augmenting quality of life after stroke.
PMID- 28697576
TI - Sparse-view image reconstruction via total absolute curvature combining total
variation for X-ray computed tomography.
AB - Sparse-view imaging is a promising scanning approach which has fast scanning rate
and low-radiation dose in X-ray computed tomography (CT). Conventional L1-norm
based total variation (TV) has been widely used in image reconstruction since the
advent of compressive sensing theory. However, with only the first order
information of the image used, the TV often generates dissatisfactory image for
some applications. As is widely known, image curvature is among the most
important second order features of images and can potentially be applied in image
reconstruction for quality improvement. This study incorporates the curvature in
the optimization model and proposes a new total absolute curvature (TAC) based
reconstruction method. The proposed model contains both total absolute curvature
and total variation (TAC-TV), which are intended for better description of the
featured complicated image. As for the practical algorithm development, the
efficient alternating direction method of multipliers (ADMM) is utilized, which
generates a practical and easy-coded algorithm. The TAC-TV iterations mainly
contain FFTs, soft-thresholding and projection operations and can be launched on
graphics processing unit, which leads to relatively high performance. To evaluate
the presented algorithm, both qualitative and quantitative studies were performed
using various few view datasets. The results illustrated that the proposed
approach yielded better reconstruction quality and satisfied convergence property
compared with TV-based methods.
PMID- 28697577
TI - Priority-based Mojette reconstruction from sparse noisy projections.
AB - Sparse-view Computed Tomography (CT) plays an important role in industrial
inspection and medical diagnosis. However, the established reconstruction
equations based on traditional Radon transform are ill-posed and obtain an
approximate solution in the case of finite sampling angles. By contrast, Mojette
transform is considered as the discrete geometry of the projection and
reconstruction lattice. It determines the geometrical conditions for ensuring a
unique solution instead of solving an ill-posed problem from the start.
Therefore, Mojette transform results in theoretical exact image reconstruction in
the discrete domain, and approximately gets the minimum number of projections, as
well as their directions. However, the reconstruction method utilizing Mojette
transform is very sensitive to noise. To address the problem, the paper proposes
a sparse-view Mojette inversion algorithm based on the minimum noise accumulation
by selecting the prioritized projections for an image reconstruction.
Experimental results show that the proposed method can effectively suppress the
noise accumulation without increasing the number of projections and produce
better reconstruction results than traditional corner-based Mojette inversion
(CBI).
PMID- 28697578
TI - Data correlation based noise level estimation for cone beam projection data.
AB - BACKGROUND: In regularized iterative reconstruction algorithms, the selection of
regularization parameter depends on the noise level of cone beam projection data.
OBJECTIVE: Our aim is to propose an algorithm to estimate the noise level of cone
beam projection data. METHODS: We first derived the data correlation of cone beam
projection data in the Fourier domain, based on which, the signal and the noise
were decoupled. Then the noise was extracted and averaged for estimation. An
adaptive regularization parameter selection strategy was introduced based on the
estimated noise level. Simulation and real data studies were conducted for
performance validation. RESULTS: There exists an approximately zero-energy double
wedge area in the 3D Fourier domain of cone beam projection data. As for the
noise level estimation results, the averaged relative errors of the proposed
algorithm in the analytical/MC/spotlight-mode simulation experiments were 0.8%,
0.14% and 0.24%, respectively, and outperformed the homogeneous area based as
well as the transformation based algorithms. Real studies indicated that the
estimated noise levels were inversely proportional to the exposure levels, i.e.,
the slopes in the log-log plot were -1.0197 and -1.049 with respect to the short
scan and half-fan modes. The introduced regularization parameter selection
strategy could deliver promising reconstructed image qualities. CONCLUSIONS:
Based on the data correlation of cone beam projection data in Fourier domain, the
proposed algorithm could estimate the noise level of cone beam projection data
accurately and robustly. The estimated noise level could be used to adaptively
select the regularization parameter.
PMID- 28697579
TI - Can low-dose CT perfusion imaging accurately assess response of advanced gastric
cancer with neoadjuvant chemotherapy?
AB - PURPOSE: To explore the value of low-dose CT perfusion imaging (LDCTPI)
technology and its perfusion parameters in assessing response of neoadjuvant
chemotherapy (NAC) in patients with advanced gastric cancer (AGC). METHODS:
Thirty patients with AGC were studied prospectively by LDCTPI to measure two
parameters including blood flow (BF) and blood volume (BV) of tumor area before
and after chemotherapy, respectively. All of the patients received two courses of
NAC and surgical resection of gastric tumor within one week after chemotherapy,
and then obtained the result of postoperative pathology response for
chemotherapy. The comparisons of BF and BV values of AGC before and after
chemotherapy were analyzed by paired-samples t-test, respectively; and the
correlations between BF as well as BV decrease rates after NAC and the pathology
response grade were analyzed by Spearman statistical test. Thirty patients were
divided into effective and ineffective groups according to different pathology
response grade. Comparisons of BF as well as BV decrease rates between effective
and ineffective groups were analyzed by independent-samples t-test, respectively.
Receiver operating characteristic (ROC) curves were used to determine the cutoff
values of BF and BV decrease rates as evaluation indicators of AGC after NAC and
calculate area under the curve (AUC). RESULTS: There were significant differences
in BF and BV values of AGC between before and after NAC (p < 0.001),
respectively, and there were obvious correlations between BF as well as BV
decrease rates and pathology response grade (r = 0.660, p < 0.001; r = 0.706, p <
0.001), respectively. There were also significant differences in BF and BV
decrease rates of AGC between effective and ineffective groups (P = 0.001),
respectively. If BF decrease rate of 12.1% (AUC was 0.816, P = 0.005) was used as
the cutoff value for chemotherapy effectiveness of AGC, the sensitivity of 82%
and specificity of 84% were achieved, and if BV decrease rate of 32.8% (AUC was
0.844, P = 0.002) was used as the cutoff value for chemotherapy effectiveness of
AGC, the sensitivity of 82% and specificity of 89% were achieved. CONCLUSIONS: BF
and BV decrease rates have potential to be used as effective indicators to assess
chemotherapy efficacy of AGC from the hemodynamics.
PMID- 28697580
TI - Medical imaging technology shock and volatility of macro economics: Analysis
using a three-sector dynamical stochastic general equilibrium REC model.
AB - The study analysed the medical imaging technology business cycle from 1981 to
2009 and found that the volatility of consumption in Chinese medical imaging
business was higher than that of the developed countries. The volatility of gross
domestic product (GDP) and the correlation between consumption and GDP is also
higher than that of the developed countries. Prior to the early 1990s the
volatility of consumption is even higher than GDP. This fact makes it difficult
to explain the volatile market using the standard one sector real economic cycle
(REC) model. Contrary to the other domestic studies, this study considers a three
sector dynamical stochastic general equilibrium REC model. In this model there
are two consumption sectors, whereby one is labour intensive and another is
capital intensive. The more capital intensive investment sector only introduces
technology shocks in the medical imaging market. Our response functions and Monte
Carlo simulation results show that the model can explain 90% of the volatility of
consummation relative to GDP, and explain the correlation between consumption and
GDP. The results demonstrated the significant correlation between the
technological reform in medical imaging and volatility in the labour market on
Chinese macro economy development.
PMID- 28697581
TI - Altered gray matter volume and functional connectivity of the motor network in
young divers.
AB - BACKGROUND: Motor learning and professional sports training can induce plastic
changes in brain structures that are associated with distinct training demands.
OBJECTIVE: To testify the hypothesis of that regional gray matter structures in
the motor-related cortex and its functional connectivity (FC) are altered in
young divers. METHODS: We undertook T1-voxel-based morphometry (VBM) structural
and resting-state functional magnetic resonance imaging in groups of diving
athletes (DAs) and demographically-matched healthy controls. RESULTS: Gray matter
volume was lower in some regions in Das. By selecting the five most reduced
regions, i.e. superior frontal gyrus, orbitofrontal cortex (OFC), insula,
hippocampus, and cerebellum posterior lobe, as regions of interest (ROIs) for FC
analysis, results showed that DAs had greater FC between the inferior temporal
gyrus and superior frontal gyrus, OFC and cerebellum posterior lobe. Conversely,
the divers had lesser FC between OFC and putamen, superior frontal gyrus and
caudate. CONCLUSIONS: VBM differences suggest that diving training entails more
effective synaptic and/or neuronal pruning processes in motor structures. Indeed,
cortical volumetric decreases in the DAs group are associated with increased FC
among certain motor-related regions. We conclude that motor learning in
adolescence alters brain structure in association with changes in FC between the
relevant cortical and subcortical regions.
PMID- 28697582
TI - The role of inorganic nitrogen in successful formation of granular biofilms for
wastewater treatment that support cyanobacteria and bacteria.
AB - Recently, the use of phototrophs for wastewater treatment has been revisited
because of new approaches to separate them from effluent streams. One
manifestation uses oxygenic photogranules (OPGs) which are dense, easily
settleable granular biofilms of cyanobacteria, which surrounding populations of
heterotrophs, autotrophs, and microalgae. OPGs can remove COD and nitrogenous
compounds without external aeration. To better grow and maintain biomass in the
proposed wastewater process, this study seeks to understand the factors that
contribute to successful granulation. Availability of initial inorganic nitrogen,
particularly ammonium, was associated with successful cultivation of OPGs. In the
first days of granulation, a decrease in ammonium coupled with an increase in a
cyanobacterial-specific 16S rRNA gene, may suggest that ammonium was assimilated
in cyanobacteria offering a competitive environment for growth. Though both
successful and unsuccessful OPG formation demonstrated a shift from non
phototrophic bacterial dominated communities on day 0 to cyanobacterial dominated
communities on day 42, the successful community had a greater relative abundance
(46%) of OTUs associated with genera Oscillatoria and Geitlernema than the
unsuccessful community (27%), supporting that filamentous cyanobacteria are
essential for successful OPG formation. A greater concentration of chlorophyll b
in the unsuccessful OPG formation suggested a greater abundance of algal species.
This study offers indicators of granulation success, notably availability of
inorganic nitrogen and chlorophyll a and b concentrations for monitoring the
health and growth of biomass for a potential OPG process.
PMID- 28697583
TI - The gut microbiota in larvae of the housefly Musca domestica and their horizontal
transfer through feeding.
AB - House fly larvae provide a prolific and sustainable source of proteins used in
poultry and fish feed. Wheat bran is a superior diet for house fly larvae and has
been widely investigated to exploit its potential in the food and feed area.
Using Illumina MiSeq 16S rDNA sequencing, this study investigated the gut
microbiota of house fly larvae feeding on wheat bran and the bacterial community
in the wheat bran. The bacterial communities in the house fly larvae were
dominated by the phyla Proteobacteria and Firmicutes. Enterobacteriaceae and
Providencia were the predominant bacteria at the family and genus levels,
respectively. Some bacteria in the phyla Actinobacteria, Proteobacteria,
Bacteroidetes and Firmicutes may be transferred from the gut of house flies to
the wheat bran during feeding and may be involved in degrading and utilizing
polysaccharides in the cell wall of wheat bran. The significance of the gut
microbiota of house fly larvae, their transferring and roles in degradation of
wheat bran is discussed. These findings regarding the gut microbiota of house fly
larvae will provide opportunities for research on the impact of microbial
communities on poultry and fish.
PMID- 28697584
TI - Genetic evidence for a novel competence inhibitor in the industrially important
Bacillus licheniformis.
AB - Natural genetic competence renders bacteria able to take up and, in case there is
sufficient homology to the recipient's chromosome, integrate exogenously supplied
DNA. Well studied in Bacillus subtilis, genetic competence is-in several aspects
known to be differently regulated in Bacillus licheniformis. We now report on the
identification of a novel, chromosomally encoded homolog of a competence
inhibitor in B. licheniformis (ComI) that has hitherto only been described as a
plasmid borne trait in the ancestral B. subtilis NCIB3610. Bioinformatical
analysis that included 80 Bacillus strains covering 20 different species revealed
a ComI encoding gene in all of the examined B. licheniformis representatives, and
was identified in few among the other species investigated. The predicted ComI of
B. licheniformis is a highly conserved peptide consisting of 28 amino acids.
Since deletion of comI in B. licheniformis DSM13 resulted in twofold increased
transformation efficiency by genetic competence and overexpression resulted in
threefold decreased transformability, the function as a competence inhibitor
became evident.
PMID- 28697585
TI - Isolation and characterization of Arctic microorganisms decomposing bioplastics.
AB - The increasing amount of plastic waste causes significant environmental
pollution. In this study, screening of Arctic microorganisms which are able to
degrade bioplastics was performed. In total, 313 microorganisms were isolated
from 52 soil samples from the Arctic region (Spitsbergen). Among the isolated
microorganisms, 121 (38.66%) showed biodegradation activity. The ability of clear
zone formation on emulsified poly(butylene succinate-co-adipate) (PBSA) was
observed for 116 microorganisms (95.87%), on poly(butylene succinate) (PBS) for
73 microorganisms (60.33%), and on poly(E-caprolactone) (PCL) for 102
microorganisms (84.3%). Moreover, the growth of microorganisms on poly(lactic
acid) (PLA) agar plates was observed for 56 microorganisms (46.28%). Based on the
16S rRNA sequence, 10 bacterial strains which showed the highest ability for
biodegradation were identified as species belonging to Pseudomonas sp. and
Rhodococcus sp. The isolated fungal strains were tested for polycaprolactone
films and commercial corn and potato starch bags degradation under laboratory
conditions. Strains 16G (based on the analysis of a partial 18S rRNA sequence,
identified as Clonostachys rosea) and 16H (identified as Trichoderma sp.) showed
the highest capability for biodegradation. A particularly high capability for
biodegradation was observed for the strain Clonostachys rosea, which showed 100%
degradation of starch films and 52.91% degradation of PCL films in a 30-day shake
flask experiment. The main advantage of the microorganisms isolated from Arctic
environment is the ability to grow at low temperature and efficient
biodegradation under this condition. The data suggest that C. rosea can be used
in natural and laboratory conditions for degradations of bioplastics.
PMID- 28697586
TI - Quality evaluation of Alpinia oxyphylla after Aspergillus flavus infection for
storage conditions optimization.
AB - In the storage of Alpinia oxyphylla, growth of mildew (especially toxic fungi,
such as Aspergillus flavus) is a potential safety risk. Few reports have
investigated how A. oxyphylla storage conditions impact mold growth or how mold
growth impacts the bioactive components of A. oxyphylla. In this study,
sterilized A. oxyphylla samples were contaminated by artificial inoculation of A.
flavus spores. The main chemical components and aflatoxin levels in the infected
A. oxyphylla samples were characterized. Central composite design-response
surface methodology was used to study the effects of different temperature and
humidity of storage conditions on the fungal growth in A. oxyphylla and
accumulation of aflatoxins. The results showed that aflatoxins levels can be
minimized by storing samples at temperatures below 25 degrees C and with
humidity less than 85%. Additionally, we found that the yield and composition of
volatile oil in A. oxyphylla exhibited small changes due to mold growth. However,
polysaccharide content reduced remarkably. Temperatures below 25 degrees C and
humidity below 85% were the best storage conditions to preventing A. oxyphylla
from becoming moldy. Our results provide the theoretical basis for future studies
the effects of storage conditions and mold growth on the quality and safety of
traditional Chinese medicines (TCMs).
PMID- 28697587
TI - Detection of bacterial sulfatase activity through liquid- and solid-phase colony
based assays.
AB - Bacterial arylsulfatases are crucial to biosynthesis in many microorganisms, as
bacteria often utilize aryl sulfates as a source of sulfur. The bacterial
sulfatases are associated with pathogenesis and are applied in many areas such as
industry and agriculture. We developed an activity-based probe 1 for detection of
bacterial sulfatase activity through liquid- and solid-phase colony-based assays.
Probe 1 is hydrolyzed by sulfatase to generate fluorescent N-methyl isoindole,
which is polymerized to form colored precipitates. These fluorescent and
colorimetric properties of probe 1 induced upon treatment of sulfatases were
successfully utilized for liquid-phase sulfatase activity assays for colonies and
lysates of Klebsiella aerogenes, Mycobacterium avium and Mycobacterium smegmatis.
In addition, probe 1 allowed solid-phase colony-based assays of K. aerogenes
through the formation of insoluble colored precipitates, thus enabling accurate
staining of target colonies under heterogeneous conditions.
PMID- 28697588
TI - Detecting Spatially Localized Exciton in Self-Organized InAs/InGaAs Quantum Dot
Superlattices: a Way to Improve the Photovoltaic Efficiency.
AB - This paper reports on experimental and theoretical investigations of atypical
temperature-dependent photoluminescence properties of multi-stacked InAs quantum
dots in close proximity to InGaAs strain-relief underlying quantum well. The
InAs/InGaAs/GaAs QD heterostructure was grown by solid-source molecular beam
epitaxy (SS-MBE) and investigated via photoluminescence (PL), spectroscopic
ellipsometry (SE), and picosecond time-resolved photoluminescence. Distinctive
double-emission peaks are observed in the PL spectra of the sample. From the
excitation power-dependent and temperature-dependent PL measurements, these
emission peaks are associated with the ground-state transition from InAs QDs with
two different size populations. Luminescence measurements were carried out as
function of temperature in the range of 10-300 K by the PL technique. The low
temperature PL has shown an abnormal emission which appeared at the low energy
side and is attributed to the recombination through the deep levels. The PL peak
energy presents an anomalous behavior as a result of the competition process
between localized and delocalized carriers. We propose the localized-state
ensemble model to explain the usual photoluminescence behaviors. The quantitative
study shows that the quantum well continuum states act as a transit channel for
the redistribution of thermally activated carriers. We have determined the
localization depth and its effect on the application of the investigated
heterostructure for photovoltaic cells. The model gives an overview to a possible
amelioration of the InAs/InGaAs/GaAs QDs SCs properties based on the theoretical
calculations.
PMID- 28697589
TI - Postpartum family planning: missed opportunities across the continuum of care
AB - Introduction: Postpartum family planning is defined as the prevention of
unintended pregnancies and closely spaced pregnancies during the first 12 months
following childbirth. Objectives: To assess the practice of family planning (FP)
by postpartum mothers in the Regional Director of Health Services (RDHS)
division, Kalutara, Sri Lanka. Methods: A community-based, descriptive, cross
sectional study was carried out among mothers, 8 to 12 weeks postpartum, in the
RDHS division, Kalutara in 2014. Calculated sample size was 1200 and the
participants were recruited using cluster sampling method. They were interviewed
at their residence about their practice of FP methods using an interviewer
administered questionnaire. Results: The response rate was 93.7% (n=1112) of
which 730 (65.6%) were practicing a FP method at 8-12 weeks after delivery.
Condoms were the most popular modern FP method (30.4%, n=222) followed by
intrauterine device (26.7%, n=195) and depot medroxyprogesterone acetate (DMPA)
injections (22.9%, n=167). Approximately 80% had utilized government sector FP
services. Women with higher level of education (p< 0.05), lower family income (p<
0.01), parity more than 3 (p< 0.001) and more than three living children (p<0.01)
were significantly more likely to use a FP method. Conclusions: Prevalence of
postpartum FP is not satisfactory. Therefore, FP services should consider
reaching postpartum mothers with unmet needs as a priority and ensure that a wide
range of contraceptive options are available to them. Postpartum FP should be
considered as a continuum of maternal care.
PMID- 28697590
TI - Prevalence of Fragile X Syndrome among children receiving special education and
carrier states in first degree relatives.
AB - Introduction: Fragile X syndrome (FXS) is a genetically determined developmental
disorder. Underlying genotype is cytosine-guanine-guanine (CGG) repeat expansions
with over 200 repeats in the fragile X mental retardation 1 (FMR1) gene. Children
with FXS are most accessible in special education institutions in Sri Lanka, with
a total of approximately 6000 registered attendees. Objectives: The aim of the
current study was to estimate the prevalence of FXS among special school
attendeesand to screen first degree relatives of affected children. Methods: A
nationally representative sample of 850 children (5-18 years) was selected using
multi-level stratified sampling. Screening was performed by 3' direct triplet
primed PCR, followed by melting curve analysis. Expanded repeat status of the
screened positives were confirmed using capillary electrophoresis, methylation
specific PCR and Southern hybridization. Screening of available first degree
relatives (n=12) were carried out using the same method of screening and
diagnosis. Results: Eleven had FXS. Prevalence of FXS was 1.3% (95% CI 0.9-1.6).
Among the 11 with FXS 9 had more than 350 CGG repeats, while the rest had around
300. Twelve first degree relatives consisting of nine mothers, two female
siblings and a male sibling were tested. All mothers and female siblings had
either full mutation or premutation while the male sibling had CGG repeats in the
normal range. Conclusions: Among the special school attendees, prevalence of FXS
was 1.3% which has a high risk for autism and attention deficit hyperactivity
disorder.
PMID- 28697591
TI - Predictive accuracy of Goodsall's rule for fistula-in-ano
AB - Introduction: Successful treatment of fistula-in-ano is sometimes challenging due
to difficulty in recognising the internal opening and the course of the fistula
tract. Although Goodsall's rule was accepted in the past, as a method to
determine the course of the fistula, recent data have shown conflicting results.
Objectives: To study the predictive accuracy of Goodsall's rule. Methods: A
sample of 212 patients with simple fistulae were studied. Hydrogen peroxide was
injected through the external opening and the appearance of air bubbles in the
anal canal indicated the location of the internal opening. The morphological
parameters including the site and number of internal and external opening/s and
the course of the tractwere recorded. Results: The median age of the participants
was 39 (range, 18-78) years. The majority (n=167, 78.8%) were males. Of the study
group, 63 (29.7%) had inter-sphincteric fistulae, 114 (53.8%) transphincteric
fistulae and 35 (16.5%) superficial fistulae. The overall predictive accuracy of
Goodsall's rule in our patients was 78.3%. Predictive accuracy was significantly
associated with type of fistulae with high predictive accuracy seen in
superficial fistulae (97.1%) and inter-sphincteric fistulae (84.1%) compared to
transphincteric fistulae (69.3%) (p=0.001). Predictive accuracy was significantly
higher in those with an external opening in the midline (98.2%), (p<0.001).
Conclusions: Although Goodsall's rule was not accurate in 22% of all fistulae, it
can be used as a guide in locating the path of the tract and the internal opening
in simple fistulae.
PMID- 28697593
TI - Variant of anorexia nervosa in Sri Lanka: a case series
PMID- 28697592
TI - Out-of-pocket expenditure in accessing healthcare services among Chronic Kidney
Disease patients in Anuradhapura District
AB - Introduction: Chronic Kidney Disease (CKD) has significant economic impact on
both patients' households and the country. Objectives: To assess the out-of
pocket (OOP) expenditure of accessing health services among CKD patients in
Anuradhapura District Methods: This community based cross-sectional study
included a representative sample of 1174 registered CKD patients from all 19
Medical Officer of Health areas in the District of Anuradhapura. Trained para
medical staff visited the households and administered an interviewer administered
questionnaire to gather information. Results: A total of 1118 CKD patients
participated. Mean age was 58.3 (SD 10.8) years. Fifty nine (5.3%) patients had
been hospitalized during the six months preceding data collection. The total OOP
for a hospital admission for one patient was Rs. 3625 (IQR 1650-8760). Thirty
eight (3.4%) patients were on dialysis. The median direct cost per patient for an
episode of dialysis was Rs.595 (IQR 415-995) while the median direct cost for a
dialysis patient per month was Rs.5490 (IQR 3950-10934). In the study population
a total of 1095 (98.0%) had attended clinic at least once during the six months
preceding the study. The OOP expenditure for a single clinic visit for one
patient was Rs.434 (IQR 200-860). Conclusions: CKD patients living in the
Anuradhapura District spent significant amounts on accessing health care which
can worsen their economic hardships. Planned interventions are warranted in order
to improve their quality of life and financial situation.
PMID- 28697594
TI - An unusual outbreak of Rickettsial infection among army soldiers engaged in
reconnaissance mission in Northern Sri Lanka
PMID- 28697595
TI - The Effect of a Receding Saline Lake (The Salton Sea) on Airborne Particulate
Matter Composition.
AB - The composition of ambient particulate matter (PM) and its sources were
investigated at the Salton Sea, a shrinking saline lake in California. To
investigate the influence of playa exposure on PM composition, PM samples were
collected during two seasons and at two sites around the Salton Sea. To
characterize source composition, soil samples were collected from local playa and
desert surfaces. PM and soil samples were analyzed for 15 elements using mass
spectrometry and X-ray diffraction. The contribution of sources to PM mass and
composition was investigated using Al-referenced enrichment factors (EFs) and
source factors resolved from positive matrix factorization (PMF). Playa soils
were found to be significantly enriched in Ca, Na, and Se relative to desert
soils. PMF analysis resolved the PM10 data with four source factors, identified
as Playa-like, Desert-like, Ca-rich, and Se. Playa-like and desert-like sources
were estimated to contribute to a daily average of 8.9% and 45% of PM10 mass,
respectively. Additionally, playa sources were estimated to contribute to 38-68%
of PM10 Na. PM10 Se concentrations showed strong seasonal variations, suggesting
a seasonal cycle of Se volatilization and recondensation. These results support
the importance of playas as a source of PM mass and a controlling factor of PM
composition.
PMID- 28697597
TI - Core-Assisted Formation of Porphyrin J-Aggregates in pH-Sensitive Polyelectrolyte
Microcapsules Followed by Fluorescence Lifetime Imaging Microscopy.
AB - A strategy assisted by an inorganic template was developed to promote the
organized self-assembly of meso-(tetrakis)-(p-sulfonatophenyl)porphyrin (TPPS) on
pH-sensitive core-shell polyelectrolyte microcapsules (PECs) of
poly(styrenesulfonate) (PSS) and poly(allylamine hydrochloride) (PAH). A key
feature of this strategy is the use of template CaCO3 microparticles as a
nucleation site endorsing inside-outside directional growth of porphyrin
aggregates. Using this approach, TPPS self-assembly in positively charged PECs
with CaCO3 (PAH/PSS)2PAH as a sequence of layers was successfully achieved using
mild pH conditions (pH 3). Evidence for porphyrin aggregation was obtained by UV
vis with the characteristic absorption bands in PECs functionalized with
porphyrins. Fluorescence lifetime imaging microscopy (FLIM) of the
polyelectrolyte core-shell confirmed the presence of radially distributed
needlelike structures sticking out from polyelectrolyte shells. Microscopic
images also revealed a sequential process (adsorption, redistribution, and
aggregation) for the directional growth (inside/outside) of TPPS aggregates,
which highlights the importance of the core in the aggregation induction.
Removing the CaCO3 core alters the porphyrin interaction in the PEC environment,
and aggregate growth is no longer favored.
PMID- 28697596
TI - Retuning the Catalytic Bias and Overpotential of a [NiFe]-Hydrogenase via a
Single Amino Acid Exchange at the Electron Entry/Exit Site.
AB - The redox chemistry of the electron entry/exit site in Escherichia coli
hydrogenase-1 is shown to play a vital role in tuning biocatalysis. Inspired by
nature, we generate a HyaA-R193L variant to disrupt a proposed Arg-His cation-pi
interaction in the secondary coordination sphere of the outermost, "distal", iron
sulfur cluster. This rewires the enzyme, enhancing the relative rate of H2
production and the thermodynamic efficiency of H2 oxidation catalysis. On the
basis of Fourier transformed alternating current voltammetry measurements, we
relate these changes in catalysis to a shift in the distal [Fe4S4]2+/1+ redox
potential, a previously experimentally inaccessible parameter. Thus,
metalloenzyme chemistry is shown to be tuned by the second coordination sphere of
an electron transfer site distant from the catalytic center.
PMID- 28697598
TI - NOX2-Mediated TFEB Activation and Vacuolization Regulate Lysosome-Associated Cell
Death Induced by Gypenoside L, a Saponin Isolated from Gynostemma pentaphyllum.
AB - Downregulation of apoptotic signal pathway and activation of protective autophagy
mainly contribute to the chemoresistance of tumor cells. Therefore, exploring
efficient chemotherapeutic agents or isolating novel natural products that can
trigger nonapoptotic and nonautophagic cell death such as lysosome-associated
death is emergently required. We have recently extracted a saponin, gypenoside L
(Gyp-L), from Gynostemma pentaphyllum and showed that Gyp-L was able to induce
nonapoptotic cell death of esophageal cancer cells associated with lysosome
swelling. However, contributions of vacuolization and lysosome to cell death
remain unclear. Herein, we reveal a critical role for NADPH oxidase NOX2-mediated
vacuolization and transcription factor EB (TFEB) activation in lysosome
associated cell death. We found that Gyp-L initially induced the abnormal
enlarged and alkalized vacuoles, which were derived from lipid rafts dependent
endocytosis. Besides, NOX2 was activated to promote vacuolization and mTORC1
independent TFEB-mediated lysosome biogenesis. Finally, raising lysosome pH could
enhance Gyp-L induced cell death. These findings suggest a protective role of
NOX2-TFEB-mediated lysosome biogenesis in cancer drug resistance and the tight
interaction between lipid rafts and vacuolization. In addition, Gyp-L can be
utilized as an alternative option to overcome drug-resistance though inducing
lysosome associated cell death.
PMID- 28697599
TI - Enhancement of Friction by Water Intercalated between Graphene and Mica.
AB - Common experience shows that friction converts mechanical energy into heat. The
first part of this process is vibrational excitation of atoms at the interface
between rubbing bodies. The second part is the removal of the vibration energy by
transferring it from the interface to the substrate. However, it is difficult to
disentangle the excitation and energy transfer processes. We solved this by using
a system consisting of a SiO2-terminated tip sliding over graphene deposited on
mica with intercalated water between them. The intercalated water was found to
increase friction by a factor of ~3 relative to dry mica. Density functional
theory calculations show that water broadens the spectral range of graphene
vibrations-particularly the low-frequency flexural modes-thus providing new
excitation channels and also by increasing the overlap with the atomic vibrations
of the mica substrate, which facilitates coupling and energy transfer.
PMID- 28697600
TI - Peptide-Appended Permethylated beta-Cyclodextrins with Hydrophilic and
Hydrophobic Spacers.
AB - A novel synthetic methodology, employing a combination of the strain-promoted
azide-alkyne cycloaddition and maleimide-thiol reactions, for the preparation of
permethylated beta-cyclodextrin-linker-peptidyl conjugates is reported. Two
different bifunctional maleimide cross-linking probes, the polyethylene glycol
containing hydrophilic linker bicyclo[6.1.0] nonyne-maleimide and the hydrophobic
5'-dibenzoazacyclooctyne-maleimide, were attached to azide-appended permethylated
beta-cyclodextrin. The successfully introduced maleimide function was exploited
to covalently graft a cysteine-containing peptide (Ac-Tyr-Arg-Cys-Amide) to
produce the target conjugates. The final target compounds were isolated in high
purity after purification by isocratic preparative reverse-phase high-performance
liquid chromatography. This novel synthetic approach is expected to give access
to many different cyclodextrin-linker peptides.
PMID- 28697601
TI - Synthesis and Characterization of Contorted Pentabenzo-Fused Coronenes as
Semiconducting Materials.
AB - Here, we report the synthesis and characterization of a series of contorted, yet
noncentrosymmetrical, polycyclic aromatic hydrocarbons with a pentabenzo-fused
coronene as the core framework. The parent pentabenzo[a,d,g,j,m]coronene (PBC)
compound is shown to exhibit a shifted and rotated type of pi-pi stacking
interactions, which render this series a semiconducting material. Single-crystal
based field-effect transistor devices of PBC exhibited efficient charge transport
behavior, giving a p-channel field-effect mobility of 0.42 cm2 V-1 s-1 and an
on/off ratio of 105.
PMID- 28697602
TI - Organocatalysis in Inert C-H Bond Functionalization.
AB - As two coexisting and fast-growing research fields in modern synthetic chemistry,
the merging of organocatalysis and C-H bond functionalization is well
foreseeable, and the joint force along this line has been demonstrated to be a
powerful approach in making inert C-H bond functionalization more viable,
predictable, and selective. In this review, we provide a comprehensive summary of
organocatalysis in inert C-H bond functionalization over the past two decades.
The review is arranged by types of inert C-H bonds including alkane C-H, arene C
H, and vinyl C-H as well as those activated benzylic C-H, allylic C-H, and C-H
bonds alpha to the heteroatom such as nitrogen and oxygen. In each section, the
discussion is classified by the explicit organocatalytic mode involved.
PMID- 28697603
TI - Introduction: CH Activation.
PMID- 28697606
TI - Dysphonia in adults with developmental stuttering: A descriptive study.
AB - BACKGROUND: Persons with stuttering (PWS) often present with other co-occurring
conditions. The World Health Organization's (WHO) International Classification of
Functioning, Disability and Health (ICF) proposes that it is important to
understand the full burden of a health condition. A few studies have explored
voice problems among PWS, and the characteristics of voices of PWS are relatively
unknown. The importance of conducting future research has been emphasised.
OBJECTIVES: This study aimed to describe the vocal characteristics of PWS.
METHOD: Acoustic and perceptual data were collected during a comprehensive voice
assessment. The severity of stuttering was also determined. Correlations between
the stuttering severity instrument (SSI) and the acoustic measurements were
evaluated to determine the significance. Twenty participants were tested for this
study. RESULT: Only two participants (10%) obtained a positive Dysphonia Severity
Index (DSI) score of 1.6 or higher, indicating that no dysphonia was present,
while 90% of participants (n = 18) scored lower than 1.6, indicating that those
participants presented with dysphonia. Some participants presented with weakness
(asthenia) of voice (35%), while 65% presented with a slightly strained voice
quality. Moderately positive correlations between breathiness and SSI (r = 0.40,
p = 0.08) have been reported. In addition, participants with high SSI scores also
scored a poor DSI of below 1.6, as observed by a moderate positive correlation
between SSI and DSI (r = 0.41). CONCLUSION: The majority of PWS presented with
dysphonia, evident in the perceptual or acoustic parameters of their voices.
These results can be used for further investigation to create awareness and to
establish intervention strategies for voice disorders among PWS.
PMID- 28697604
TI - Palladium-Catalyzed Transformations of Alkyl C-H Bonds.
AB - This Review summarizes the advancements in Pd-catalyzed C(sp3)-H activation via
various redox manifolds, including Pd(0)/Pd(II), Pd(II)/Pd(IV), and Pd(II)/Pd(0).
While few examples have been reported in the activation of alkane C-H bonds, many
C(sp3)-H activation/C-C and C-heteroatom bond forming reactions have been
developed by the use of directing group strategies to control regioselectivity
and build structural patterns for synthetic chemistry. A number of mono- and
bidentate ligands have also proven to be effective for accelerating C(sp3)-H
activation directed by weakly coordinating auxiliaries, which provides great
opportunities to control reactivity and selectivity (including
enantioselectivity) in Pd-catalyzed C-H functionalization reactions.
PMID- 28697607
TI - Wideband acoustic immittance for assessing middle ear functioning for preterm
neonates in the neonatal intensive care unit.
AB - BACKGROUND: The primary aim of newborn hearing screening is to detect permanent
hearing loss. Because otoacoustic emissions (OAEs) and automated auditory
brainstem response (AABR) are sensitive to hearing loss, they are often used as
screening tools. On the other hand, false-positive results are most often because
of transient outer- and middle ear conditions. Wideband acoustic immittance
(WAI), which includes physical measures known as reflectance and absorbance, has
shown potential for accurate assessment of middle ear function in young infants.
OBJECTIVE: The main objective of this study was to determine the feasibility of
WAI as a diagnostic tool for assessing middle ear functioning in preterm neonates
in the neonatal intensive care unit (NICU) designed for premature and ill
neonates. A further objective was to indicate the difference between the
reflectance values of tones and click stimuli. METHOD: Fifty-six at-risk neonates
(30 male and 26 female), with a mean age at testing of 35.6 weeks (range: 32-37
weeks) and a standard deviation of 1.6 from three private hospitals, who passed
both the distortion product otoacoustic emission (DPOAE) and AABR tests, were
evaluated prior to discharge from the NICU. Neonates who presented with abnormal
DPOAE and AABR results were excluded from the study. WAI was measured by using
chirp and tone stimuli. In addition to reflectance, the reflectance area index
(RAI) values were calculated. RESULTS: Both tone and chirp stimuli indicated high
power reflectance values below a frequency of 1.5 kHz. Median reflectance reached
a minimum of 0.67 at 1 kHz - 2 kHz but increased to 0.7 below 1 kHz and 0.72
above 2 kHz for the tone stimuli. For chirp stimuli, the median reflectance
reached a minimum of 0.51 at 1 kHz - 2 kHz but increased to 0.68 below 1 kHz and
decreased to 0.5 above 2 kHz. A comparison between the present study and previous
studies on WAI indicated a substantial variability across all frequency ranges.
CONCLUSION: These WAI measurements conducted on at-risk preterm NICU neonates
(mean age at testing: 35.6 weeks, range: 32-37 weeks) identified WAI patterns not
previously reported in the literature. High reflective values were obtained
across all frequency ranges. The age of the neonates when tested might have
influenced the results. The neonates included in the present study were very
young preterm neonates compared to the ages of neonates in previous studies. WAI
measured in at-risk preterm neonates in the NICU was variable with environmental
and internal noise influences. Transient conditions affecting the sound
conduction pathway might have influenced the results. Additional research is
required to investigate WAI testing in ears with and without middle ear
dysfunction. The findings of the current study imply that in preterm neonates it
was not possible to determine the feasibility of WAI as a diagnostic tool to
differentiate between ears with and without middle ear pathology.
PMID- 28697608
TI - Spatiotemporal patterns of clinical bovine dermatophilosis in Zimbabwe 1995-2014.
AB - A retrospective study of clinical bovine dermatophilosis outbreaks and cases for
the period 1995-2014 was conducted, using data obtained from the Division of
Veterinary Services (DVS). A total of 3856 outbreaks and 26 659 cases of
dermatophilosis were reported countrywide during this period. The post rainy
season accounted for 37.9% of the outbreaks followed by the rainy season (26.7%),
cold dry season (22.1%) and the hot dry season (13.2%). A retrospective space
time scan statistic in SaTScanTM was used to detect clusters. From this study, it
was evident that dermatophilosis was spreading from the north-west of Zimbabwe
through the central to the north-east during the period 2010-2014. Five clusters
were identified mainly in the central and north-western regions of Zimbabwe. The
primary cluster was centred at Ungwe, Gokwe district in Midlands; the second,
third, fourth and fifth likely clusters were centred at Bonga (Mashonaland
Central), ARDA (Mashonaland West), Nsenga (Matabeleland North) and Zanda in
Gokwe, respectively. The findings of this study suggest the continued spread of
dermatophilosis across the country; as such the Department of Livestock and
Veterinary Services are advised to develop measures aimed at managing this spread
such as dipping, quarantine, movement control and raising farmer awareness.
PMID- 28697609
TI - Differential virulence and tsetse fly transmissibility of Trypanosoma
congolense and Trypanosoma brucei strains.
AB - African animal trypanosomiasis causes significant economic losses in sub-Saharan
African countries because of livestock mortalities and reduced productivity.
Trypanosomes, the causative agents, are transmitted by tsetse flies (Glossina
spp.). In the current study, we compared and contrasted the virulence
characteristics of five Trypanosoma congolense and Trypanosoma brucei isolates
using groups of Swiss white mice (n = 6). We further determined the vectorial
capacity of Glossina pallidipes, for each of the trypanosome isolates. Results
showed that the overall pre-patent (PP) periods were 8.4 +/- 0.9 (range, 4-11)
and 4.5 +/- 0.2 (range, 4-6) for T. congolense and T. brucei isolates,
respectively (p < 0.01). Despite the longer mean PP, T. congolense-infected mice
exhibited a significantly (p < 0.05) shorter survival time than T. brucei
infected mice, indicating greater virulence. Differences were also noted among
the individual isolates with T. congolense KETRI 2909 causing the most acute
infection of the entire group with a mean +/- standard error survival time of 9
+/- 2.1 days. Survival time of infected tsetse flies and the proportion with
mature infections at 30 days post-exposure to the infective blood meals varied
among isolates, with subacute infection-causing T. congolense EATRO 1829 and
chronic infection-causing T. brucei EATRO 2267 isolates showing the highest
mature infection rates of 38.5% and 23.1%, respectively. Therefore, our study
provides further evidence of occurrence of differences in virulence and
transmissibility of eastern African trypanosome strains and has identified two,
T. congolense EATRO 1829 and T. brucei EATRO 2267, as suitable for tsetse
infectivity and transmissibility experiments.
PMID- 28697610
TI - Phylogenetic analysis of a partial L1 gene from bovine papillomavirus type 1
isolated from naturally occurring papilloma cases in the northwestern region of
Turkey.
AB - This study was aimed at the molecular characterisation of bovine papillomavirus
type 1 (BPV-1) isolated from papilloma cases in the northwestern region of
Turkey. BPV-1 is a widely occurring oncogenic virus in cattle and is associated
with benign epithelial neoplasia which causes significant economic losses in
dairy and beef cattle because of treatment costs. In this study, 29 suspected
papilloma specimens were collected from cattle in northwestern Turkey. These
samples underwent molecular characterisation via the polymerase chain reaction
(PCR) and sequencing analysis as well as macroscopic and histopathological
examination. The histopathological examinations confirmed papilloma as the main
lesion type in the specimens. Of the 29 papilloma-like tissue samples that were
collected, 11 (i.e. 37.93%) were detected as positive and determined as
containing BPV-1 (11 of 11, 100%). Using a partial sequence for the L1 gene
acquired from GenBank, phylogenetic analysis confirmed the presence of BPV-1 and
revealed that the infection might have originated in cross bred domestic and
imported cattle. This study provides potentially useful information on the origin
and spread of this disease. Its results can potentially aid in the development of
appropriate control measures and therapeutic or vaccination strategies against
the BPV-1 strain of bovine papillomatosis.
PMID- 28697611
TI - Comparison of cow-side diagnostic tests for subclinical mastitis of dairy cows in
Musanze district, Rwanda.
AB - Four subclinical mastitis diagnostic tests (the UdderCheck(r) test [a lactate
dehydrogenasebased test], the California Mastitis Test [CMT], the Draminski(r)
test [a conductivity-based test] and the PortaSCC(r) test [a portable somatic
cell count-based test]) were compared in a study comprising crossbreed dairy cows
(n = 30) during September and October 2015. Sensitivity and specificity of the
CMT, Draminski(r) and UdderCheck(r) tests were compared with the PortaSCC(r) as
reference. The CMT, Draminski(r) and UdderCheck(r) test results were compared
with the results of the PortaSCC(r) test using kappa statistics. Duplicate
quarter milk samples (n = 120) were concurrently subjected to the four tests.
Sensitivity and specificity were 88.46% and 86.17% (CMT), 78.5% and 81.4%
(Draminski(r)) and 64.00% and 78.95% (UdderCheck(r)). The CMT showed substantial
agreement (k = 0.66), the Draminski(r) test showed moderate agreement (k = 0.48)
and the UdderCheck(r) test showed fair agreement (k = 0.37) with the PortaSCC(r)
test and positive likelihood ratios were 6.40, 4.15 and 3.04, respectively. The
cow-level subclinical mastitis prevalence was 70%, 60%, 60% and 56.7% for
PortaSCC(r), CMT, Draminski(r) and UdderCheck(r) tests, respectively. At udder
quarter level, subclinical mastitis prevalence was 20%, 21.67% and 20.83% for
PortaSCC(r), CMT and UdderCheck(r), respectively. A correlation (P < 0.05) and
moderate strength of association were found between the four tests used. The
study showed that compared to the PortaSCC(r) test, the CMT was the most
preferable option, followed by the Draminski(r) test, while the UdderCheck(r)
test was the least preferable option for subclinical mastitis screening.
PMID- 28697612
TI - Seroprevalence of Rhodococcus equi in horses in Israel.
AB - Rhodococcus equi is a common cause of pneumonia in foals and has extensive
clinical, economic and possibly zoonotic consequences. This bacterium survives
well in the environment and may be considered as normal flora of adult horses.
Certain strains of this bacterium are extremely virulent in foals, and early
identification and intervention is crucial for prognosis. Rhodococcus equi is
endemic in many parts of the world and occasionally isolated in Israel. This
study was designed to evaluate R. equi seroprevalence in adult horses in Israel
to indirectly indicate the potential level of exposure of susceptible foals. Sera
were collected from 144 horses during spring 2011 and from 293 horses during fall
2014, and the presence of antibodies against virulent R. equi was detected by
enzyme-linked immunosorbent assay. Equine seroprevalence of R. equi was found to
be 7.6% in 2011 and 5.1% in 2014. Only one farm had seropositive horses in 2011,
whereas several farms had seropositive horses in 2014. No significant risk
factors for seropositivity were found. Rhodococcus equi appears to be endemic in
Israel. This is the first survey of R. equi in Israel that provides information
on the epidemiology of this important bacterium.
PMID- 28697613
TI - Relationship between age and brainstem allometry in the African grasscutter
(Thryonomys swinderianus Temminck, 1827).
AB - Allometric values of brainstem structures were evaluated in African grasscutters
Thryonomys swinderianus (n = 27). Brain samples were extracted from 9 animals
each of 3 days (neonates), 72 days (juveniles) and 450 days of age (adults). The
midbrain, pons and medulla oblongata were separated from each brain sample and
dimensions and weights obtained. The weights of the midbrain in the neonate,
juvenile and adult African grasscutters were 0.33 g +/- 0.01 g, 0.47 g +/- 0.01 g
and 0.93 g +/- 0.02 g, respectively. The increase from neonate to juvenile (p =
0.002) and adult (p = 0.003) was significant. The pons lengths in the neonate,
juvenile and adult were 2.05 mm +/- 0.05 mm, 3.86 mm +/- 0.05 mm and 4.16 mm +/-
0.22 mm, respectively. There was a significant increase in the length of the pons
from the neonate to the juvenile (p = 0.002), but the increase from the juvenile
to the adult period was not significant (p = 0.263). There was also a significant
(p < 0.05) increase in the weights and lengths of the medulla oblongata from
neonate to juvenile and adult periods. In adults, the nose-rump length and the
length of the medulla were significantly negatively correlated (r2 = 0.47; p =
0.043). The present study concluded that the postnatal development of some
brainstem structures in the African grasscutter varies with age.
PMID- 28697614
TI - Genetic variation in and relationships among faecal worm eggs recorded in
different seasons of the year at the Tygerhoek farm in South Africa.
AB - Gastrointestinal nematodes result in severe economic and production losses to the
sheep industry. An increase in resistance of the nematodes to chemicals used for
control, as well as a demand of consumers for meat products free from chemicals,
has fostered research on alternative control strategies. Breeding for resistance
to nematodes offers an alternative to control parasitism but its effectiveness
depends on genetic variation in faecal worm egg count (FWEC), an indirect measure
of parasite resistance. A historic dataset of FWEC from four Merino lines
subjected to natural parasite challenge was used to estimate genetic parameters
for FWEC in three seasons (autumn, winter and spring) using a repeated records
animal model, followed by a three-trait animal model analysis treating FWEC in
different seasons as separate traits. The effects of selection line, birth year,
sex, the sex x birth year interaction, season and the season x year interaction
were significant when using 4994 records recorded from 1997 to 2000 (p < 0.001).
The heritability of log-transformed FWEC amounted to 0.09 +/- 0.02, with no
contribution from the animal permanent environmental variance to the between
animal variation across seasons. Three-trait heritability estimates for log
transformed FWEC amounted to 0.07 +/- 0.05 in autumn, 0.13 +/- 0.05 in winter and
0.19 +/- 0.05 in spring. These results suggest sufficient genetic variation in
FWEC to support selection for lower log-transformed FWEC. However, the best time
to record data for selection is after the break of the season in winter and in
spring, when sheep are stimulated by a greater intake of infective larvae from
the pasture after the first rains. Genetic correlations among FWEC in the
respective seasons were moderate to high, ranging from 0.55 to 0.89. Phenotypic
correlations, on the other hand, were significant but lower in magnitude, ranging
from 0.09 to 0.16. These results provide useful information for developing
strategies for the genetic improvement of ovine resistance to gastrointestinal
nematodes under Mediterranean conditions in South Africa by using FWEC as an
indicator trait.
PMID- 28697615
TI - Predictors of burnout among HIV nurses in the Western Cape.
AB - BACKGROUND: Burnout has been implicated as one of the reasons for key healthcare
personnel, such as nurses, leaving their profession, resulting in insufficient
staff to attend to patients. OBJECTIVE: We investigated the predictors of three
dimensions of burnout, namely emotional exhaustion, depersonalisation and
personal accomplishment, among nurses in South Africa attending to patients
living with HIV. METHOD: Participants were recruited at a large tertiary hospital
in the Western Cape region, with the help of the assistant director of nursing at
the hospital. They completed the Maslach Burnout Inventory, the Quantitative
Workload Inventory, the Interpersonal Conflict at Work Scale, the Organisational
Constraints Scale, the Death and Dying subscale of the Nursing Stress Scale, and
the HIV and AIDS Stigma Instrument - Nurse. RESULTS: We found elevated levels of
burnout among the sample. Workload, job status and interpersonal conflict at work
significantly explained more than one-third of the variance in emotional
exhaustion (R2 = 0.39, F(7, 102) = 9.28, p = 0.001). Interpersonal conflict,
workload, organisational constraints and HIV stigma significantly explained
depersonalisation (R2 = 0.33, F(7, 102) = 7.22, p = 0.001). Job status and
organisational constraints significantly predicted personal accomplishment (R2 =
0.18, F(7, 102) = 3.12, p = 0.001). CONCLUSION: Factors such as workload, job
status and interpersonal conflict in the work context, organisational constraints
and stigma associated with HIV were found to be predictors of burnout in the
sample of nurses. Our recommendations include developing and testing
interventions aimed at reducing burnout among nurses, including reducing workload
and creating conditions for less interpersonal conflict at work.
PMID- 28697616
TI - Perceptions, attitudes and challenges about obesity and adopting a healthy
lifestyle among health workers in Pietermaritzburg, KwaZulu-Natal province.
AB - BACKGROUND: The prevalence of obesity is reported to be high and increasing among
health workers, in both high-income and low-income countries, which in turn is a
common risk factor for all non-communicable diseases. This is alarming, as health
workers not only serve the community's health needs but should also serve as role
models for a healthy lifestyle. It is therefore important that obesity among
health workers is addressed and prevented. OBJECTIVE: The aim of the study was to
explore perceptions and attitudes about obesity among health workers in three
selected hospitals in Pietermaritzburg, and to identify the barriers to adopting
a healthy lifestyle. METHODS: An explorative and descriptive qualitative study
design was used, utilising in-depth interviews for data collection. A total of 18
health workers from the three selected hospitals in the metropolitan were
individually interviewed. Thematic analysis was done, using a priori themes that
were derived from the Health Belief Model. RESULTS: All health workers were aware
of the negative consequences of being overweight or obese. However, only a few of
the participants chose to adopt a healthy lifestyle. Barriers to adopting a
healthy lifestyle included institutional as well as attitudinal factors.
CONCLUSION: Public healthcare facilities need to invest in their work force by
giving health workers access to physical exercise facilities and affordable
healthy food within the hospital. Health organisations should introduce health
behaviour change programmes to combat negative established cultural norms among
health staff.
PMID- 28697617
TI - Dietary habits among health professionals working in a district hospital in
KwaZulu-Natal, South Africa.
AB - INTRODUCTION: The burden of diseases associated with unhealthy lifestyle
behaviours continues to increase in the low- and middle-income countries
including South Africa. Among the affected population are the health
professionals who are assumed to be knowledgeable about healthy eating. AIM: This
study aimed to determine the dietary habits of health professionals in a public
district hospital in KwaZulu-Natal, South Africa. METHODS: A cross-sectional
survey was conducted in 2012 among 109 randomly selected health professionals.
Each received a questionnaire consisting of mostly closed and few open-ended
questions. Its main focus was the dietary and eating habits of the professionals.
An ethical clearance was granted by the Medunsa Research and Ethics committee at
the University of Limpopo. Permission to conduct the study was sought and
obtained from participants as well. Descriptive statistics and frequencies were
used to analyse data. RESULTS: A 100% (109) response rate was achieved. The
majority skipped meals especially breakfast with a significant positive
correlation between breakfast intake per week and age (r = 0.98, p = 0.048). The
majority consumed a lot of unhealthy foods and carbonated beverages with sugar.
Consumption of fruits, vegetables, high fibre and whole grain foods was less
common. CONCLUSION: The study showed poor eating habits among participants.
Urgent health interventions are therefore indicated to highlight the importance
of healthy eating habits among the entire population.
PMID- 28697618
TI - Evaluation of a Zulu translation of the Parents' Evaluation of Developmental
Status.
AB - BACKGROUND: One of the greatest challenges in early communication intervention in
South Africa is developing and implementing successful identification strategies
in primary health care (PHC). A shortage of trained PHC personnel is one of the
barriers to providing adequate health services in South Africa. This dearth of
services creates the need to substitute clinician-administered developmental
screening tools with parent-administered tools. AIM: To determine the accuracy of
the Zulu Parents' Evaluation of Developmental Status (PEDS) in comparison with
the outcome of the English PEDS. SETTING: The data were collected in a clinical,
non-contrived environment at Stanza Bopape Community Health Clinic in Mamelodi,
City of Tshwane. METHODS: The PEDS is a standardised, parent-completed
questionnaire regarding the child's general development. The English PEDS was
translated into Zulu by a Zulu linguist. There were 99 potential participants in
the study of whom 83 met the necessary prerequisites. RESULTS: Of the
participants whose home language is Zulu, 54% preferred the PEDS in English over
the PEDS in Zulu. This indicates a skewed preference towards English, with only
slight associations between language preference and age, education and home
language. CONCLUSION: The Zulu PEDS displayed high positive and negative
correspondences, representative of an accurate translation of the English PEDS.
It is recommended that this study should be repeated in a community where the
majority are Zulu home language speakers.
PMID- 28697619
TI - Investigating the accessibility factors that influence antenatal care services
utilisation in Mangwe district, Zimbabwe.
AB - BACKGROUND: Maternal and infant mortality remains a huge public health problem in
developing countries. One of the strategies to minimise the risks of both
maternal and infant mortality is access to and utilisation of antenatal care
(ANC) services. AIM: This study aimed to investigate the accessibility factors
that influence the use of ANC services in Mangwe district. METHODS: A qualitative
approach using explorative design was adopted to target women who have babies
under 1 year of age. The study was conducted in Mangwe district, Matabeleland
South province, Zimbabwe. Data were collected through semi-structured interviews
and observations. Data saturation was reached after 15 women who were
conveniently sampled were interviewed. Field notes were analysed thematically
using Tech's steps. Lincoln and Guba's criteria ensured trustworthiness of the
study findings. RESULTS: Accessibility factors such as lack of transport, high
transport costs and long distances to health care facilities, health care
workers' attitudes, type and quality of services as well as delays in receiving
care influence women's utilisation of ANC services in Mangwe district, Zimbabwe.
CONCLUSION: The study concluded that women were still facing problems of
unavailability of nearby clinics; therefore, it was recommended that the
government should avail resources for women to use. RECOMMENDATIONS: Mangwe
District Health Department should provide mobile clinics rendering ANC services
in distant rural areas.
PMID- 28697620
TI - Is it just religious practice? Exploring patients' reasons for choosing a faith
based primary health clinic over their local public sector primary health clinic.
AB - BACKGROUND: Person-centred, re-engineered primary health care (PHC) is a national
and global priority. Faith-based health care is a significant provider of PHC in
sub-Saharan Africa, but there is limited published data on the reasons for
patient choice of faith-based health care, particularly in South Africa. AIM: The
primary objective was to determine and explore the reasons for patient choice of
a faith-based primary care clinic over their local public sector primary care
clinic, and secondarily to determine to what extent these reasons were influenced
by demography. SETTING: The study was conducted at Jubilee Health Centre (JHC), a
faith-based primary care clinic attached to Jubilee Community Church in Cape
Town, South Africa. METHODS: Focus groups, using the nominal group technique,
were conducted with JHC patients and used to generate ranked reasons for
attending the clinic. These were collated into the top 15 reasons and
incorporated into a quantitative questionnaire which was administered to adult
patients attending JHC. RESULTS: A total of 164 patients were surveyed (a
response rate of 92.4%) of which 68.3% were female and 57.9% from the Democratic
Republic of the Congo (DRC). Of patients surveyed, 98.2% chose to attend JHC
because 'the staff treat me with respect', 96.3% because 'the staff are friendly'
and 96.3% because 'the staff take time to listen to me'. The reason 'it is a
Christian clinic' was chosen by 70.1% of patients. 'The staff speak my home
language' was given as a reason by 61.1% of DRC patients and 37.1% of South
African patients. 'The clinic is close to me' was chosen by 66.6% of Muslims and
40.8% of Christians. CONCLUSION: Patients chose to attend JHC (a faith-based
primary care clinic) because of the quality of care received. They emphasised the
staff-patient relationship and patient-centredness rather than the clinic's
religious practices (prayer with patients). These findings may be important in
informing efforts to improve public sector primary care.
PMID- 28697621
TI - Undiagnosed tuberculosis in patients with HIV infection who present with severe
anaemia at a district hospital.
AB - BACKGROUND: Tuberculosis (TB) is a major cause of severe anaemia in patients with
human immunodeficiency virus (HIV) infection in South Africa. However, TB can be
difficult to diagnose as it may be extra pulmonary and paucibacillary. AIM: The
aim of this study was to investigate undiagnosed TB in patients with HIV
infection and severe anaemia and to identify the optimal investigations for
diagnosing TB. SETTING: Mthatha General Hospital, a district hospital. METHODS:
The study was a case series. RESULTS: Haemoglobin levels ranged from 3.6 g/dL to
7.9 g/dL, the mean CD4 count was 176 cells/MUL and 80% of patients had a positive
TB symptom screen. Forty-three (86%) patients had either clinical or
bacteriologically proven TB of whom 33 had pulmonary TB, 34 had extra pulmonary
TB and 24 had both types. The diagnostic yield for TB was: chest X-ray (CXR) 91%;
ultrasound (US) abdomen pericardium and lower chest 62%; sputum Xpert MTB/RIF
35%; TB blood culture 21% and TB urine culture 15%. Blood and urine cultures did
not identify any additional cases over those identified by CXR and US. The
laboratory turnaround times were as follows: sputum Xpert, 1.6 days; blood
culture, 20 days and urine culture, 28 days. CXR and US were done within one day
of initial patient assessment. CONCLUSIONS: The majority of HIV patients with
severe anaemia had TB disease, and extra pulmonary TB was as prevalent as
pulmonary TB. CXR, US and sputum Xpert were the optimum tests for rapid diagnosis
of TB. South African national TB/HIV guidelines should incorporate these specific
tests to diagnose TB in patients with HIV and severe anaemia.
PMID- 28697622
TI - Phytochemical analysis of Saponaria officinalis L. shoots and flowers essential
oils.
AB - Phytochemical analysis by GC and GC/MS of the essential oil samples obtained from
fresh shoots and flowers of Saponaria officinalis L. allowed the identification
of 96 components in total, comprising 94.7% and 86.0% of the total oils
compositions, respectively. Regarding the shoots essential oil, the major of 87
identified volatile compounds were phytol (14.1%), tricosane-6,8-dione (13.4%),
patchouli alcohol (7.9%) and tricosane (7.2%), whereas patchouli alcohol (20.0%),
heneicosane (11.5%) and tricosane (8.4%) were dominant among the 66 volatiles in
the flower oil. Nonterpenoid compounds had the highest contribution in S.
officinalis shoots essential oil (53.7%), while in the flower oil, constituents
were almost evenly distributed between the oxygenated sesquiterpenoid (41.2%) and
nonterpenoid compounds (39.5%).
PMID- 28697623
TI - Influence of sensory quality on preferences for apples of primary school
children.
AB - In this research work, sensorial features of four varieties of fresh apples have
been investigated by children aged 6-10 years (n = 336) of the Centre-East region
of Italy (Abruzzo). The examined sensory properties were visual appealing,
aromatic flavour, sourness, sweetness, firmness and crunchiness. Statistical
analysis was performed by means of principal component analysis which underlined
the differences and similarities between the examined fruits and the most
responsive variables. Results are very interesting and allow to better understand
the most important descriptors which influence the appreciation of the different
tested varieties. Furthermore, it has been noted that different varieties
influence each other for the perception of some sensory characteristics. Thus,
improving the knowledge of the most appreciated organoleptic properties of apples
by young consumers would be very useful and it might stimulate the development of
new and more appealing cultivars in the future.
PMID- 28697624
TI - Evaluating a novel intervention to reduce trauma symptoms and sexual risk taking:
qualitative exit interviews with sexual minority men with childhood sexual abuse.
AB - Childhood sexual abuse (CSA) continues to affect sexual minority men (SMM) at
disproportionate levels and contributes to multiple negative health outcomes,
including sexual-risk taking and HIV acquisition. This paper presents qualitative
evaluative feedback from SMM (N = 9) who participated in a 10-session Cognitive
Behavioral Therapy-Trauma and Sexual Health (CBT-TSH) intervention to reduce CSA
related posttraumatic stress reaction and distress. The treatment was designed to
increase accurate sexual risk appraisals and to improve self-care health
behaviors related to HIV/STI acquisition. The researchers identified four
emerging themes: (1) motivation to participate, (2) response to cognitive
therapy, (3) process of change, and (4) considerations for intervention
improvement. These qualitative findings provide useful feedback on the
acceptability of an innovative program that integrates CBT for trauma related to
CSA with sexual risk-reduction counseling.
PMID- 28697625
TI - Effects of Structured Versus Unstructured Self-Monitoring of Blood Glucose on
Glucose Control in Patients With Non-insulin-treated Type 2 Diabetes: A Meta
Analysis of Randomized Controlled Trials.
AB - BACKGROUND: The use of self-monitoring of blood glucose (SMBG) in patients with
non-insulin-treated type 2 diabetes is debated. Meta-analyses of randomized
clinical trials (RCTs) suggest a small reduction of HbA1c in patients using SMBG,
without considering potential confounders, such as SMBG regimen and use of SMBG
data to adjust diabetes medications. METHODS: A meta-analysis was performed
including RCTs in patients with non-insulin-treated type 2 diabetes, with an
intervention of >=24 weeks and HbA1c as the primary endpoint, to verify the
effect of SMBG (vs no monitoring), structured SMBG (vs unstructured), and of SMBG
driven therapy adjustments. RESULTS: In RCTs (n = 8) comparing SMBG with no SMBG
(1277 and 1072 patients, respectively), SMBG reduced HbA1c by -0.17% (95% CI
0.25 to -0.09%, P < .003). The reduction in HbA1c was greater in RCTs (n = 3) in
which SMBG data were used to adjust diabetes medications (HbA1c decrease: -0.3%
[95% CI -0.49 to -0.1%]) than in RCTs (n = 6) where SMBG data were not used for
this purpose (HbA1c decrease: -0.1% [95% CI -0.2 to 0.0%]) ( P < .005). In the
RCTs comparing structured and unstructured SMBG (757 and 750 patients,
respectively), in which structured SMBG data were also used to adjust diabetes
medications, the HbA1c difference between groups at study end was -0.27% (95% CI
0.49 to -0.04%, P < .018). CONCLUSIONS: In RCTs performed in non-insulin-treated
patients with type 2 diabetes, SMBG is associated with a significant, although
small, reduction in HbA1c. HbA1c reduction was greater with structured SMBG and
when structured SMBG data were used to adjust diabetes therapy.
PMID- 28697626
TI - Newspaper Articles Related to the Not Criminally Responsible on Account of Mental
Disorder (NCRMD) Designation: A Comparative Analysis.
AB - OBJECTIVE: The not criminally responsible on account of mental disorder (NCRMD)
designation remains widely misunderstood by the public. Such misunderstandings
may also be reflected in the media. As such, the aim of this study is to conduct
a preliminary examination of the tone and content of recent Canadian newspaper
articles where NCRMD is a major theme, comparing these to generic articles about
mental illness. METHODS: Articles about mental illness were gathered from major
Canadian newspapers. These were then divided into two categories: 1) articles
where NCRMD was a major theme and 2) articles where NCRMD was not a major theme.
Articles were then coded for the presence or absence of 1) a negative tone, 2)
stigmatising tone/content, 3) recovery/rehabilitation as a theme, and 4) shortage
of resources/poor quality of care as a theme. RESULTS: The retrieval strategy
resulted in 940 articles. Fourteen percent ( n = 131) of all articles had NCRMD
as a major theme. In comparison to generic articles about mental illness,
articles with NCRMD as a major theme were significantly more likely to have a
negative tone ( P < 0.001) and stigmatising tone/content ( P < 0.001) and
significantly less likely to have recovery/rehabilitation ( P < 0.001) or
shortage of resources/poor quality of care as a theme ( P < 0.001). CONCLUSIONS:
Articles with NCRMD as a theme were overwhelmingly negative and almost never
focused on recovery or rehabilitation, in stark comparison to generic articles
about mental illness.
PMID- 28697627
TI - Launching an SBNS-accredited neurosurgical skills workshop for medical students
and foundation trainees.
AB - The Neurology and Neurosurgery Interest Group (NANSIG), the student arm of the
Society of British Neurological Surgeons (SBNS), organised a neurosurgical skills
workshop in January 2017 following evidence of high demand among medical students
and foundation trainees. The workshop involved ten delegates and five
neurosurgical trainees with one senior consultant. Modules covering head
positioning, burr holes, ventricular access, and flaps were included. This
'Introduction to Neurosurgery' skills workshop demonstrated significantly
improved knowledge and confidence of delegates with attending and assisting in
theatre in the future.
PMID- 28697628
TI - High dose alcohol consumption predicts less reduction in post-traumatic stress
symptoms after a campus mass shooting.
AB - BACKGROUND: Recognizing that alcohol might affect subsequent processing of trauma
related information, this study examined whether high dose alcohol consumption
(HDAC) following a campus mass shooting affected the relation between shooting
exposure and post-traumatic stress symptoms (PTSS). METHODS: Female participants
(N = 691) recorded levels of physical exposure to the shooting event, alcohol
use, and PTSS 1 month following the shooting event and 8 months later. RESULTS:
No evidence was found to suggest that pre-shooting HDAC moderated the
relationship between trauma exposure and PTSS 1 month following the shooting.
HDAC in the month following the shooting predicted less resolution of PTSS 8
months later. Specifically, at higher (but not lower) levels of HDAC, shooting
exposure was associated with less reduction in PTSS from 1 to 8 months post
trauma. Several alternate explanations were ruled out. CONCLUSIONS: Less
reduction in PTSS seems to occur at high levels of both shooting exposure and
HDAC. Theoretical implications and directions for future research are discussed.
PMID- 28697629
TI - Culturally and linguistically diverse student and family perspectives of AAC.
AB - Augmentative and alternative communication (AAC) devices are important for
nonverbal students with disabilities to communicate with the verbal world. AAC
devices provide access to academic and social opportunities for students with
disabilities. With the changing demographics of schools and an emphasis on
meaningful, culturally relevant instruction for all students, it is important to
consider how AAC devices are utilized and perceived by individuals from
culturally and linguistically diverse (CLD) backgrounds and their families. This
paper reviewed empirical studies that addressed the perspectives and use of AAC
devices by CLD students with disabilities and their families. A total of N = 11
studies were selected spanning almost two decades of research related to AAC use
in culturally and linguistically diverse populations internationally. Discussions
and implications highlight the need for a deeper understanding of culture and
race as they inform instruction for AAC users with disabilities and additional
current studies related to this critical topic within the field.
PMID- 28697630
TI - UHPLC-MS/MS phenolic profiling and in vitro antioxidant activities of Inula
graveolens (L.) Desf.
AB - Inula graveolens (L.) Desf. is an annual aromatic herb which has various uses on
alternative medicine in many region of the world. In this study, antioxidant
activities of ethanol and water extracts of the plant leaves were determined by
in vitro DPPH method and phenolic composition of the plant sample was determined
by LC-MS/MS analysis. The results showed that chlorogenic acid, quinic acid,
hyperoside, protocatechuic acid and quercetin were the major phenolic compounds
among the 27 standard compounds. The significant antioxidant capacity of the
plant might be related with the high abundance of phenolic compounds.
PMID- 28697631
TI - Recent advances on biomedical applications of scaffolds in wound healing and
dermal tissue engineering.
AB - The tissue engineering field has developed in response to the shortcomings
related to the replacement of the tissues lost to disease or trauma: donor tissue
rejection, chronic inflammation and donor tissue shortages. The driving force
behind the tissue engineering is to avoid the mentioned issues by creating the
biological substitutes capable of replacing the damaged tissue. This is done by
combining the scaffolds, cells and signals in order to create the living,
physiological, three-dimensional tissues. A wide variety of skin substitutes are
used in the treatment of full-thickness injuries. Substitutes made from skin can
harbour the latent viruses, and artificial skin grafts can heal with the
extensive scarring, failing to regenerate structures such as glands, nerves and
hair follicles. New and practical skin scaffold materials remain to be developed.
The current article describes the important information about wound healing
scaffolds. The scaffold types which were used in these fields were classified
according to the accepted guideline of the biological medicine. Moreover, the
present article gave the brief overview on the fundamentals of the tissue
engineering, biodegradable polymer properties and their application in skin wound
healing. Also, the present review discusses the type of the tissue engineered
skin substitutes and modern wound dressings which promote the wound healing.
PMID- 28697632
TI - Deployment Status and Child Neglect Types in the U.S. Army.
AB - Increases in combat deployments have been associated with rises in rates of child
neglect in U.S. military families. Although various types of child neglect have
been described in military families, it is unknown whether deployment status is
associated with specific types of child neglect and whether other factors, such
as substance misuse, play a role. To determine the contribution of service member
deployment status to the risk of specific child neglect types, data were
collected from 390 substantiated U.S. Army child neglect case files. The
contributions of deployment status at the time of the neglect incident and
parental alcohol or drug-related misuse to risk of neglect types were examined
controlling for military family rank and child age. Compared to never deployed
families, families with a service member concurrently deployed at the time of the
neglect incident were at higher risk for failure to provide physical needs, lack
of supervision, and educational neglect, but at lower risk for emotional neglect.
Being previously deployed incurred risk for moral-legal neglect. Substance misuse
added risk for moral-legal and educational neglect. Findings indicate the need
for tailored prevention strategies to target different periods within the
deployment cycle.
PMID- 28697633
TI - Zinc L-carnosine suppresses inflammatory responses in lipopolysaccharide-induced
RAW 264.7 murine macrophages cell line via activation of Nrf2/HO-1 signaling
pathway.
AB - CONTEXT: Zinc L-carnosine (ZnC) is a chelate of Zn and L-carnosine and is used
clinically in the treatment of peptic ulcer. OBJECTIVE: In this study, we aim to
investigate the involvement of heme oxygenase-1 (HO-1) in the anti-inflammatory
effects of ZnC in lipopolysaccharide (LPS)-induced RAW 264.7 murine macrophages.
MATERIALS AND METHODS: We used immunoblotting analysis to evaluate the
involvement of HO-1 in the anti-inflammatory effects of ZnC and the signaling
pathway involved was measured using Dual luciferase reporter assay. RESULTS:
Results from immunoblotting analysis demonstrated that pretreatment of cells with
ZnC enhanced the expression of HO-1 in RAW 264.7 cells. Pretreatment of cells
with HO-1 inhibitor (tin protoporphyrin IX dichloride) significantly attenuated
the inhibitory effects of ZnC on nitric oxide (NO) production, inducible nitric
oxide synthase (iNOS) expression and NF-kappaB activation in LPS-induced RAW
264.7 cells, suggesting that HO-1 play an important role in the suppression of
inflammatory responses induced by ZnC. Furthermore, results from co
immunoprecipitation of Nrf2 and Keap1 and dual luciferase reporter assay showed
that pretreatment of ZnC was able to activate the Nrf2 signaling pathway.
Treatment of cells with p38 inhibitor (SB203580), c-Jun N-terminal kinase
inhibitor (SP600125), and MEK 1/2 inhibitor (U0126) did not significantly
suppress the induction of HO-1 by ZnC. Moreover, our present findings suggest
that the effects of ZnC on NO production, HO-1 expression, and Nrf2 activation
were attributed to its Zn subcomponent, but not l-carnosine. CONCLUSION:
Pretreatment with ZnC was able to activate Nrf2/HO-1 signaling pathway, thus
suppressing the expression of inflammatory mediators, such as NO and iNOS in LPS
induced RAW 264.7 cells.
PMID- 28697634
TI - The fibrinolysis inhibitor alpha2-antiplasmin restricts lymphatic remodelling and
metastasis in a mouse model of cancer.
AB - Remodelling of lymphatic vessels in tumours facilitates metastasis to lymph
nodes. The growth factors VEGF-C and VEGF-D are well known inducers of lymphatic
remodelling and metastasis in cancer. They are initially produced as full-length
proteins requiring proteolytic processing in order to bind VEGF receptors with
high affinity and thereby promote lymphatic remodelling. The fibrinolytic
protease plasmin promotes processing of VEGF-C and VEGF-D in vitro, but its role
in processing them in cancer was unknown. Here we explore plasmin's role in
proteolytically activating VEGF-D in vivo, and promoting lymphatic remodelling
and metastasis in cancer, by co-expressing the plasmin inhibitor alpha2
antiplasmin with VEGF-D in a mouse tumour model. We show that alpha2-antiplasmin
restricts activation of VEGF-D, enlargement of intra-tumoural lymphatics and
occurrence of lymph node metastasis. Our findings indicate that the fibrinolytic
system influences lymphatic remodelling in tumours which is consistent with
previous clinicopathological observations correlating fibrinolytic components
with cancer metastasis.
PMID- 28697635
TI - The perpetuation of the misconception that rats receive a 3-5 times lower lung
tissue dose than humans at the same ozone concentration.
AB - This paper highlights the pervasive misconception concerning 1994 findings from
Hatch et al. about ozone (O3) tissue dose in humans versus rats. That study
exposed humans to 0.4 ppm and rats to 2 ppm 18O-labeled O3 and found comparable
incorporation of 18O into bronchoalveolar lavage constituents. However, during O3
exposure humans were exercising, which increased their ventilation rate five
fold, while rats were at rest. This resulted in similar O3 tissue doses between
the two species, and predominantly explained the comparable 18O incorporation at
five-fold different concentrations. The five-times higher exercising human
inhalation rate offset the five-times lower concentration, producing the same
human dose expected at rest at 2 ppm (i.e. 0.4 ppm * 4686 L/2 hour ~ 2 ppm * 998
L/2 hour). In 2013, Hatch et al. showed that resting humans and resting rats
experienced fairly comparable 18O incorporation at the same O3 exposure
concentration and activity state into BALF cells. Despite these findings, we show
here that in the peer-reviewed literature a substantial proportion of researchers
continue to perpetuate the misunderstanding that human lung tissue doses of O3
are simply 3-5 times greater than rat doses at the same O3 concentration, due to
interspecies differences, and not considering activity state. It is important to
correct this misconception to ensure an appropriate understanding of the
implications of O3 studies by the scientific community and policy experts making
regulatory decisions (e.g. the US Environmental Protection Agency's National
Ambient Air Quality Standards for O3).
PMID- 28697636
TI - Increasing dietary EPA and DHA influence estimated fatty acid desaturase activity
in systemic organs which is reflected in the red blood cell in mice.
AB - Delta-5 (D5D) and delta-6 (D6D) desaturase are key enzymes in fatty acid (FA)
metabolism. Dietary eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)
may alter tissue FA composition via D5D and D6D. The purpose was to determine the
relationship between dietary EPA + DHA, estimated desaturase activities of
various tissues and the reflection of desaturase activity in the red blood cell
(RBC). Mice were fed diets with increasing percent of energy from EPA + DHA.
Phospholipid FA composition of heart, muscle, spleen, lung, adipose tissues and
RBC were analysed. D5D and D6D enzyme activity estimates (EAE) were calculated as
the ratio of 20:4/20:3 and 20:3/18:2, respectively. D5D EAE decreased in all
tissues, except muscle, with increasing dietary EPA + DHA. RBC D5D EAE positively
correlated with D5D EAE in all tissues. RBC D6D EAE positively correlated with
muscle and inversely correlated with adipose D6D EAE. Our findings suggest
differential influence of dietary EPA + DHA upon tissue desaturase activities.
PMID- 28697637
TI - Heavy + light chain analysis to assign myeloma response is analogous to the IMWG
response criteria.
AB - Automated serum heavy + light chain (HLC) immunoassays can measure the intact
immunoglobulins of each light chain type separately. We though to compare HLC
assays with electrophoretic techniques in determining International Myeloma
Working Group (IMWG) response criteria. 114 myeloma patients from 2 trials were
included. HLC measurements were made utilizing archived sera and response
assessments compared with those based on electrophoretic analysis at the time of
the trials. Assessments at ~90 days and maximal response were compared as was the
power of the 2 techniques for predicting later responses, overall survival, and
progression. The kappa statistic indicated good agreement between the 2 methods
for determining IMWG response criteria, although HLC measurements might give
better predictions of subsequent responses and frequently gave an earlier
indication of change. HLC measurements could represent an alternative to
electrophoretic techniques in determining IMWG response. Validation with a
greater range of patient responses is needed for confirmation.
PMID- 28697639
TI - Forgetting and emotion regulation in mental health, anxiety and depression.
AB - Does normal forgetting facilitate mental health and is forgetting impaired in
affective disorders? This double-sided question may seem counterintuitive given
the fact that forgetting is often associated with troubles in everyday life.
However, forgetting does not only have destructive consequences, but also fulfils
important functions. I consider the possibility that forgetting may function as a
beneficial sorting mechanism which helps healthy people discard information that
is undesirable and unpleasant. Thus, selective forgetting of negative memories
may be part of emotion regulation, that is, people's attempts to control when and
how they experience and express emotions. Such forgetting may allow for a focus
on positive memories and thereby help form a mnemonic basis for optimism as well
as active and explorative approach behaviour. Also, I consider the possibility
that anxiety and depression may in part result from and be maintained by a
diminished capacity to forget. A reduced ability to selectively forget negative
memories may be one reason that such disorders are characterised by painful
emotions such as fear and sadness as well as defensive and withdrawn behaviour.
Overall, I review and reflect on evidence for and against functional forgetting
in mental health and dysfunctional forgetting in affective disorders.
PMID- 28697638
TI - The effect of SWL and URS on health-related quality of life in proximal ureteral
stones.
AB - OBJECTIVES: We aimed to compare the effect of shock wave lithotripsy (SWL) and
ureteroscopic lithotripsy (URS) on health-related quality of life (HRQoL) for the
treatment of proximal ureteral stones. MATERIAL AND METHODS: Between April 2014
and July 2015, patients with proximal ureteral stones who were successfully
treated with URS or SWL in seven different centers were included. Patients were
divided into two groups according to stone size: stones <=10 mm and >10 mm. HRQoL
subscales which were evaluated by the Medical Outcome Study Short-Form 36-item
survey (SF-36) Turkish version were compared for URS and SWL in these two groups
one month after the performed procedure. RESULTS: A total of 273 patients were
included in the study. While 116 (52.5%) patients were treated with ureteroscopic
lithotripsy, SWL was used for 105 (47.5%) patients. Fifty-two patients were
excluded from the study. In proximal ureteral stones <=10 mm, there were no
statistically significant differences for any of the eight subscales of the SF-36
questionnaire. Regarding stones >10 mm, it was found that the three subscales of
the SF-36 questionnaire - role limitations because of physical health problems
(RP), bodily pain (BP), and general health perception (GH) - were significantly
lower in the SWL group compared with the URS group. CONCLUSIONS: Patients with
proximal ureteral stones >10 mm who were treated with URS generally may have a
more favorable HRQoL than those treated with SWL in short-term follow-up.
PMID- 28697640
TI - On Bayesian Simplicity in Human Visual Perceptual Organization.
AB - A returning idea among some Bayesians in research on human visual perceptual
organization is that the surprisal of something (i.e., the negative logarithm of
its probability) expresses its complexity (i.e., the length of its shortest
description). Bayes' rule is a powerful modeling tool and descriptive simplicity
is a rich concept, but this idea is wishful thinking at best: If true, it would
unify the simplicity and likelihood principles, which reflect two traditionally
opposed schools of thought on perceptual organization. Some rapprochement between
the two principles can certainly be discerned, but the aforementioned idea lacks
formal underpinning and confounds otherwise perfectly good ideas. Here, this idea
is revisited and its latest version is debunked step by step. In addition, I
argue that its likely origin lies, inadvertently, in a standard Bayesian
textbook: The author made (a) a pivotal mistake and (b) a compelling argument
that was overinterpreted by others.
PMID- 28697641
TI - Erectile Dysfunction in Young Myocardial Infarction Survivors: Evaluation, Follow
Up.
AB - Erectile dysfunction significantly affects quality of life in young men. Authors
have evaluated erectile function in men with coronary artery disease (CAD) and
the relationship between the degree of erectile dysfunction (ED) and the age of
their first acute myocardial infarction (AMI). The incidence of erectile
dysfunction in three groups of patients of AMI survivors was investigated: AMI
survivors younger than 45 years, AMI survivors older than 65 years, and normal
male population aged between 30 and 60 years. Erectile function was assessed by
the International Index of Erectile Function (IIEF-5) questionnaire. In post-AMI
male patients younger than 45 years ( n = 76), mild ED occurred in 26% and severe
in 7%. In the older AMI group, mild ED occurred in 52% and severe in 38%. In the
control group age matched to younger survivors, 96% denied ED and only one
control patient had a score of 20 on the IIEF-5. A paradoxical result was
observed in patients using beta blockers (BB), who had better scores than the
group without BB. Statin treatment had a positive influence on the score in
questionnaires. Those on statins had an average score of 21.0 +/- 4.9 vs. without
statin 17.7 +/- 5.7, p = .03. The current findings identified that the prevalence
of ED is relatively high in young patients with CAD and is related to treatment
of the CAD. The overall increase in ED presence suggests that the background of
their coronary event is not due to destabilization of single focused atheroma but
may reflect a generalized atherosclerotic process.
PMID- 28697642
TI - Short-term outcomes of laparoscopic total gastrectomy for gastric cancer: a
comparative study with laparoscopic distal gastrectomy at a high-volume center.
AB - BACKGROUND: Laparoscopic distal gastrectomy (LDG) for gastric cancer has
gradually gained popularity. However, laparoscopic total gastrectomy (LTG) has
been reported rarely when compared with LDG. This study was designed to evaluate
the surgical outcomes as well as the morbidity and mortality of LTG compared with
LDG to confirm the feasibility and safety of LTG. MATERIAL AND METHODS: We
reviewed the data of patients at our institution undergoing LTG (n = 448) or LDG
(n = 956) for gastric cancer between January 2008 and July 2016. Then the
clinical characteristics and perioperative clinical outcomes of the two groups
were compared. RESULTS: Except for tumor size and stage, there were no
statistically significant differences in the clinicopathological parameters
between the groups. LTG was associated with significantly longer operation time,
late time to postoperative diet, and longer hospital stay compared with the LDG
group. Overall complications developed in 60 patients (13.4%) and surgical
complications in 48 patients (10.7%) after LTG. Postoperative complications were
less frequent in the LDG group than in the LTG group (8.4% versus 13.4%, p <
.01), and fewer surgical complications were observed with LDG than with LTG (7.5%
versus 10.7%, p = .05). CONCLUSIONS: The results of LTG were favorable even
though are not inferior to those of LDG. LTG for gastric cancer is technically
feasible and safe. However, because of the limits of this study, other high
quality studies are needed for further evaluation.
PMID- 28697643
TI - Parental Perceptions About Informed Consent/Assent in Pediatric Research in
Jordan.
AB - The informed consent/assent process during enrollment in pediatric research is
integral to protecting children from possible harm. Here we explored parents'
perceptions about the informed consent/assent process in Jordan. Therefore, focus
group interviews were conducted that focused on the importance of consent/assent,
the quality of the information provided during consent process, and the parents'
perceptions toward written/verbal informed consent. Content thematic analysis
approach was adopted in the transcription and translation processes of the
interviews. The majority of parents have an ethically acceptable understanding of
many of the aspects related to consent/assent; however, some views were not
consistent with the proper conduct of research. For example, some parents
believed that informed consent is not required for questionnaire studies.
Discrepancies were also noted regarding the appropriate age of a child's assent.
Some parents would force their child to participate. Thus, the development of
Jordanian, culturally sensitive pediatric research guidelines is required.
PMID- 28697644
TI - Evidence of absence: no relationship between behaviourally measured prediction
error response and schizotypy.
AB - INTRODUCTION: The predictive processing framework has attracted much interest in
the field of schizophrenia research in recent years, with an increasing number of
studies also carried out in healthy individuals with nonclinical psychosis-like
experiences. The current research adopted a continuum approach to psychosis and
aimed to investigate different types of prediction error responses in relation to
psychometrically defined schizotypy. METHODS: One hundred and two healthy
volunteers underwent a battery of behavioural tasks including (a) a force
matching task, (b) a Kamin blocking task, and (c) a reversal learning task
together with three questionnaires measuring domains of schizotypy from different
approaches. RESULTS: Neither frequentist nor Bayesian statistical methods
supported the notion that alterations in prediction error responses were related
to schizotypal traits in any of the three tasks. CONCLUSIONS: These null results
suggest that deficits in predictive processing associated with clinical states of
psychosis are not always present in healthy individuals with schizotypal traits.
PMID- 28697645
TI - Biomechanical investigation of prolonged driving in an ergonomically designed
truck seat prototype.
AB - A postural evaluation during a prolonged driving task was conducted to determine
the ergonomic validity of a new freely adjustable truck seat prototype. Twenty
participants were recruited to perform two 2-h simulated driving sessions.
Postures were assessed using motion capture, accelerometers and pressure pads.
Subjective discomfort was also monitored in 15-min increments using ratings of
perceived discomfort (RPD) and the Automotive Seating Discomfort Questionnaire.
Participants had a more neutral spine posture during the first hour of the drive
and reported lower RPDs while sitting in the prototype. Pairing the gluteal
backrest panel with the adjustable seat pan helped reduce the average sitting
pressure. The industry-standard truck seat may lead to the development of poor
whole body posture, and the proposed ergonomic redesign of a new truck seat
helped improve sitting posture and reduce perceived discomfort. Practitioner
Summary: A new freely adjustable truck seat prototype was compared to an Industry
standard seat to assess hypothesised improvements to sitting posture and
discomfort for long haul driving. It was found that the adjustable panels in the
prototype helped promote spine posture, reduce sitting pressure and improved
discomfort ratings.
PMID- 28697646
TI - Effects of perlite and caustic soda on microorganism activities of leachate in a
sequence batch reactor.
AB - The purpose of this article is to evaluate the effect of adsorbents and alkali
pre-treatment on microorganism activities of activated sludge (AS) for the
treatment of landfill leachate (LFL). The chemical oxygen demand (COD) and
BOD5/COD ratio of LFL used in this research were 10,500 and 0.68, respectively.
In order to survey the role of porous absorbent, perlite was employed as an
alternative with low porosity and was compared to powdered activated carbon
(PAC), which has been most widely used in the treatment process. As a result, the
COD removal efficiency increased from 32% to 47.7% when alkali LFL was loaded to
the sequence batch reactors (SBRs) at the optimum conditions of the biological
process. Also, at the same condition, both SBRs containing PAC and perlite showed
COD removals of over 81% and 72%, respectively. The specific oxygen uptake rate
(SOUR) showed that alkali pre-treatment reduces the toxicity effect of heavy
metals on microorganism activities. The adsorption capacity (the uptake of COD)
was analyzed by Langmuir and Freundlich isotherm models. Further, the kinetic
study of COD adsorption during the treatment process demonstrated that the alkali
pre-treatment of LFL proceeded faster and was intensified by the presence of
adsorbents.
PMID- 28697647
TI - Antimetabolites in the treatment of advanced pleural mesothelioma: a network meta
analysis of randomized clinical trials.
AB - An indirect comparison of cisplatin-pemetrexed (CP) and cisplatin-raltitrexed
(CR) was performed. The Odds Ratios of 10, 15 and 20 month survival rate and
response rate were assumed as indexes of efficacy; the Odds Ratio of grade III-IV
side effects, and the absolute risk of overall, hematologic and non-hematologic
toxicity, were assumed as indexes of safety. The outcomes of 352 patients were
analysed. The Odds Ratios and 95% Confidence Interval (95% CI) of 10, 15 and 20
months survival rate and response rate were 1.2 (95% CI 0.65-2.24, p = 0.559),
1.02 (95% CI 0.49-2.12, p = 0.953), 1.13 (95% CI 0.44-2.91, p = 0.805) and 0.56
(95% CI 0.26-1.21, p = 0.141), respectively. An absolute increased risk of grade
III-IV side effects was observed for CP: 6% (95% CI 3-9%, p < 0.001), 9% (95% CI
2-16%, p = 0.008) and 3% (95% CI 0-5%, p = 0.035) for overall, hematological and
non-hematological toxicity. CP and CR can be considered comparable in terms of
efficacy in the treatment of metastatic pleural mesothelioma, with a modest
increased risk of grade III-IV side effects for CP.
PMID- 28697648
TI - Long-term mortality and causes of death in endoscopically verified upper
gastrointestinal bleeding: comparison of bleeding patients and population
controls.
AB - OBJECTIVE: Upper gastrointestinal bleeding (UGIB) is a common emergency, with in
hospital mortality between 3 and 14%. However, the long-term mortality and causes
of death are unknown. We investigated the long-term mortality and causes of death
in UGIB patients in a retrospective single-centre case-control study design.
METHODS: A total of 569 consecutive patients, aged >=18 years, admitted to Kuopio
University Hospital for their first endoscopically verified UGIB during the years
2009-2011 were identified from hospital records. For each UGIB patient, an age,
sex and hospital district matched control patient was identified from the
Statistics Finland database. Data on endoscopy procedures, laboratory values,
comorbidities and medication were obtained from patient records. Data on deaths
and causes of death were obtained from Statistics Finland. RESULTS: In-hospital
mortality of UGIB patients was low at 3.3%. The long-term (mean follow-up 32
months) mortality of UGIB patients was significantly higher than controls (34.1
versus 12.1%, p < .001). During the 6 months following UGIB, the risk of death
compared to controls was highest (HR 19.2, 95% CI 7.0-52.4, p < .001) and
remained higher up to 3 years after the bleeding. Beyond 3 years' follow-up,
there was no difference in mortality between the groups (HR 0.7, 95% CI 0.4-1.6,
p = .436). During the first 3 months after the UGIB episode, mortality was
related to gastrointestinal diseases; after 3 months, the causes of death were
related to comorbidities and did not differ from causes of death in controls.
CONCLUSIONS: UGIB patients have three times higher long-term mortality than
population controls.
PMID- 28697649
TI - Enhanced photocatalytic degradation of sulfamethoxazole by deposition of Au, Ag
and Cu metallic nanoparticles on TiO2.
AB - Mono- (Au, Ag and Cu) and bi-metallic (Au-Ag and Au-Cu) nanoparticles were
deposited on TiO2 and tested for the photocatalytic degradation of
sulfamethoxazole using either UV-C or simulated sunlight. The optimal loading of
metallic nanoparticles was determined as 1.5 wt% for Au and Ag, and 1.0 wt% for
Cu. In the case of bi-metallic nanoparticles, only the ratio 1:0.5 wt% for both
Au-Ag and Au-Cu was tested. In experiments using UV-C light, the highest
degradation performance was found for Ag/TiO2, while bi-metallic nanoparticles
supported on TiO2 also showed increased photocatalytic activity compared with
unmodified TiO2. In simulated sunlight irradiation tests, Au/TiO2 showed to be
the most efficient material. Complete mineralization of sulfamethoxazole was
achieved when surface-modified materials were tested in both UV-C and simulated
sunlight experiments. Photolysis was efficient to fully degrade sulfamethoxazole,
although mineralization was lower than 10% for both luminic sources. The main by
products of sulfamethoxazole were determined in photolysis and photocatalysis
tests using UV-C light, and degradation paths were proposed. By-products showed
non-toxicity and low antibiotic activity. Reuse of the catalysts upon three
reaction cycles did not result in the loss of activity.
PMID- 28697650
TI - Ceftaroline for the treatment of osteomyelitis caused by methicillin-resistant
Staphylococcus aureus: a case series.
AB - Despite limited clinical data, ceftaroline is commonly used for treatment of
complicated, invasive infections caused by methicillin-resistant Staphylococcus
aureus (MRSA). A retrospective chart review was conducted of adult patients
receiving ceftaroline for MRSA osteomyelitis admitted between April 2011 and
March 2016 at a five-hospital system. Twelve patients met the inclusion criteria.
All patients received prior antimicrobial therapy with a median time to switch to
ceftaroline of 45.5 days. Five of the 12 patients (41.7%) met criteria for
ceftaroline failure. Patients with vertebral osteomyelitis (58%) had a longer
length of stay, longer ceftaroline treatment, but similar success rates to those
with non-vertebral osteomyelitis (57% vs. 60%). Ceftaroline is a viable
alternative for a challenging patient population that has failed or are unable to
receive other therapies.
PMID- 28697651
TI - Mucosal immune system of the gastrointestinal tract: maintaining balance between
the good and the bad.
AB - The gastrointestinal tract (GI tract) is a unique organ inhabited by a range of
commensal microbes, while also being exposed to an overwhelming load of antigens
in the form of dietary antigens on a daily basis. The GI tract has dual roles in
the body, in that it performs digestion and uptake of nutrients while also
carrying out the complex and important task of maintaining immune homeostasis,
i.e., keeping the balance between the good and the bad. It is equally important
that we protect ourselves from reacting against the good, meaning that we stay
tolerant to harmless food, commensal bacteria and self-antigens, as well as react
with force against the bad, meaning induction of immune responses against harmful
microorganisms. This complex task is achieved through the presence of a highly
efficient mucosal barrier and a specialized multifaceted immune system, made up
of a large population of scattered immune cells and organized lymphoid tissues
termed the gut-associated lymphoid tissue (GALT). This review provides an
overview of the primary components of the human mucosal immune system and how the
immune responses in the GI tract are coordinated and induced.
PMID- 28697652
TI - Ask the experts how to treat individuals with spatial neglect: a survey study.
AB - PURPOSE: Spatial neglect (SN) impedes rehabilitation success and leaves long-term
consequences. We asked experts to provide their opinions in addressing SN by
scenario (ideal vs. reality) and by recovery phase (earliest, acute, subacute,
and chronic). Experts were individuals who have assessed or treated patients with
SN clinically. MATERIALS AND METHODS: This study was conducted using an anonymous
survey on the Internet with 189 responders over 3 months. Located in 23 different
countries, 127 experts of seven disciplines were included (occupational therapy,
physical therapy, nursing, speech and language pathology or therapy, neurology,
physical medicine and rehabilitation, and psychology or neuropsychology).
RESULTS: Comparing the two scenarios, more treatments were selected in the ideal
than in the reality scenario for all recovery phases except for the chronic
phase. In both scenarios, (1) more treatments were selected in acute and subacute
phases than in earliest or chronic phases, (2) less experienced experts selected
diverse treatment options more often, and (3) highly experienced experts were
more likely to provide their reasons of treatment selection, suggestions of
treatment delivery methods, and other insights. Finally, 83.7% reported obstacles
in treating SN. CONCLUSIONS: Experts' treatment selections are consistent with
current evidence and practice guidelines. Recognizing the limitation of evidence,
their opinions may help generate ideas in various topics (e.g., dosing,
integrative intervention, and treatment implementation) to be examined in future
studies. Implications for Rehabilitation Clinicians with experience in treating
people with spatial neglect (i.e., experts as defined in the present study)
recognized the limitation of evidence but nonetheless suggested specific
treatments by recovery phase. In both the reality and ideal scenarios, experts
included visual scanning, active limb activation, and sustained attention
training in the top-five selections. Prism adaptation was in the top-five
selections in the ideal scenario, while in the reality scenario, it was in the
top-five in all phases except for the earliest phase where it was the sixth most
selected. They also shared their valuable opinions in when to use which treatment
to address spatial neglect and how to deliver certain interventions, which may
help to generate ideas in various topics (e.g., dosing, integrative intervention,
knowledge dissemination, and treatment implementation) that can be examined in
future studies. We suggest that (1) clinicians consider collective expert
opinions reported here to enhance their clinical judgment and practices, (2)
researchers develop studies focused on treatments with limited evidence but
selected here by experts, and (3) funding agencies provide the means to research
and implementation projects that will generate rich information for improving
practice guidelines and rehabilitation outcomes for patients with spatial
neglect. The majority of the experts reported some obstacles in providing
treatment for spatial neglect, and time and equipment shortages were the most
common barriers, which should be addressed at the system level to determine
whether removing those barriers have long-term beneficial impacts on both
patients and healthcare systems.
PMID- 28697653
TI - Bear tracks hypothesis: from atrial fibrillation to atrial fibrosis syndrome in
stroke risk assessment.
PMID- 28697654
TI - Acute effect of whole body vibration on postural control in congenitally blind
subjects: a preliminary evidence.
AB - PURPOSE: The purpose of this study was to investigate the acute effects of whole
body vibration at optimal frequency, on postural control in blind subjects.
METHOD: Twenty-four participants, 12 congenital blind males (Experimental Group),
and 12 non-disabled males with no visual impairment (Control Groups) were
recruited. The area of the ellipse and the total distance of the center of
pressure displacements, as postural control parameters, were evaluated at
baseline (T0), immediately after the vibration (T1), after 10 min (T10) and after
20 min (T20). Whole body vibration protocol consisted into 5 sets of 1 min for
each vibration, with 1 min rest between each set on a vibrating platform.
RESULTS: The total distance of center of pressure showed a significant difference
(p < 0.05) amongst groups, while the area remained constant. No significant
differences were detected among times of assessments, or in the interaction group
* time. CONCLUSION: No impairments in static balance were found after an acute
bout of whole body vibration at optimal frequency in blind subjects and,
consequently, whole body vibration may be considered as a safe application in
individuals who are blind.
PMID- 28697655
TI - Functional Ulnar Nerve Paraganglioma: First Documented Occurrence in the
Extremity With Hitherto Undescribed Associated Extensive Glomus Cell Hyperplasia
and Tumorlet Formation.
AB - Extra-adrenal paraganglioma has never been described in the extremities. A 34
year-old woman complained of an enlarging mass in the right forearm for 18
months. Imaging showed a circumscribed vascular tumor attached to the ulnar
nerve; biopsy revealed features of paraganglioma. The resected tumor consisted of
zellballen pattern of chief cells staining positively for chromogranin with
surrounding S100-positive sustentacular cells. The chief cells contained many
neurosecretory granules and mitochondria, whereas the sustentacular cells
contained a large amount of rough endoplasmic reticulum and some microfilaments.
There was adjacent extensive glomus cell hyperplasia and tumorlet formation. The
intraoperative blood pressure dropped abruptly on tumor removal. The serum
normetanephrine level decreased from a preoperative level of 1987 pg/mL (normal <
149 pg/mL) to normal after operation. The patient admitted on questioning to a
history of paroxysmal attacks of transient palpitation, hand tremors, and
sweating; imaging showed no evidence of tumor in other parts of the body, and
there was no family history of similar tumor; she remained well 33 months after
the operation. This occurrence of functional ulnar nerve paraganglioma with the
hitherto undescribed associated glomus cell hyperplasia and tumorlet formation
attests to the probable existence of normal sympathetic paraganglia in the
extremity and their intimate functional relationship with glomus bodies.
PMID- 28697656
TI - Impact of liver transplantation on the risk of second malignant tumors among
hepatocellular carcinoma patients.
AB - BACKGROUND: Population-based data on the development of second malignant
neoplasms (SMNs) following the diagnosis of hepatocellular carcinoma (HCC) are
uncommon. We evaluated this clinical vignette in HCC patients within the
Surveillance, Epidemiology and End Results (SEER) database. METHODS: The SEER
database (1973-2012) was queried using the SEER*Stat program to determine the
clinico-pathological features of HCC patients with more than one year survival
who developed SMNs. Standardized incidence ratios (SIRs) were calculated to
determine the risk of each type of subsequent cancers. Relative risk was assessed
to determine the impact of liver transplantation on the development of second
malignant neoplasms. RESULTS: On SIR analysis, the following sites have an
enhanced risk of developing an SMN following the diagnosis of HCC: tongue, anal
canal, liver, lung, kidney, thyroid, non-Hodgkin lymphoma (both nodal and extra
nodal disease) and acute monocytic leukemia (P < 0.05 for all sites). A
significantly higher RR was found for the development of lung cancer (RR =
2.096), thyroid cancer (RR = 3.045) and non-Hodgkin lymphoma (RR = 3.822) among
patients who underwent liver transplantation compared to those who did not (P <
0.05). CONCLUSION: There is an excess risk for developing a number of SMNs among
patients diagnosed with HCC.
PMID- 28697657
TI - Anemia and pregnancy outcomes: a longitudinal study.
AB - OBJECTIVES: To determine the prevalence of anemia at the first antenatal visit
and at 32-34 weeks gestational age, and to evaluate perinatal and maternal
outcomes. METHODS: Venous blood samples were obtained for complete blood counts
at both study visits. Maternal and perinatal morbidity and mortality were also
recorded. The data were analyzed using SPSS (version 23). RESULTS: Two thousand
pregnant women were recruited. The prevalence of anemia was 42.7% (n = 854/2000)
at the first antenatal visit. Thirty-five percent had mild anemia and 68.9% had
normocytic normochromic anemia. The prevalence of anemia in HIV infected women
was higher than that in the noninfected group and 47.2% of the study population
(n = 2000) was HIV infected. At the 32-34 weeks visit, hemoglobin (Hb) levels
were available for 1433/2000 (71.7%) of the participants. The prevalence of
anemia was 28.1% (n = 403/1433); 19.3% had mild anemia and 65.3% had normocytic
normochromic anemia. There was a significant difference in Hb levels between that
of the first visit and that at 32-34 weeks (42.7% vs. 28.1%; p = .001; 95% CI:
0.11-0.18). There were significant differences in prematurity, birth weight and
hypertensive disorders of pregnancy between the anemic and nonanemic groups.
CONCLUSION: The prevalence of anemia decreased from 42.7% (booking) to 28.1% (32
34 weeks). Normocytic normochromic anemia was the commonest type of anemia.
Attention needs to be focused on detailed investigations to establish the exact
cause of anemia.
PMID- 28697658
TI - Determining the minimum number of electrodes that need to be pitch matched to
accurately estimate pitch matches across the array.
AB - OBJECTIVE: With bilateral cochlear implant (CI) users there is typically a place
mismatch between the locations stimulated by the left and right electrode arrays.
This mismatch can affect performance, potentially limiting binaural benefits. One
way to address this is by perceptually realigning the arrays such that a given
frequency in the input stimulates perceptually matched locations in the two ears.
A clinically feasible technique is needed that can determine the appropriate
perceptual alignment. A pitch matching task can potentially be used for this, but
only if it can be performed in a clinically feasible amount of time. The
objective of this study was to determine the minimal number of electrodes that
need to be pitch matched to accurately determine pitch matches across the entire
array. DESIGN: A retrospective analysis of pitch matching data was conducted.
Subsets of pitch matches were selected and the predicted pitch matching across
the array was compared to that predicted by the full dataset. STUDY SAMPLE: 16
bilateral CI users. RESULTS: The results indicated that nine pitch matches are
sufficient, which can typically be obtained in approximately 7 min. CONCLUSION:
The results reveal a clinically feasible method for determining pitch matches
across the array.
PMID- 28697659
TI - The effect of cognitive emotion regulation strategies on gynecologic oncology:
comparison between a clinical and a non-clinical sample.
AB - OBJECTIVE: This study aimed to examine the differences of cognitive emotion
regulation (CER) strategies between patients with gynecologic cancer and non
clinical individuals. METHODS: A cohort of 329 female adults was recruited in
this study. About 179 patients with gynecologic cancer were allocated to the
clinical group and 150 healthy women were allocated to the non-clinical group.
All the participants completed a demographic survey and the Chinese version of
Cognitive Emotion Regulation Questionnaire (CERQ-C). RESULTS: There were
statistically significant group differences in the CER strategies used between
the two groups. The most prevalent discrepancies of the CER strategies across the
two samples were the self-blame, rumination, putting into perspective,
catastrophizing, and blaming others. Further logistic regression analyzes
indicated that these four strategies have significant and independent
contributions to the prediction of group membership. In particular, a higher
reported use of self-blame and blaming others, and a lower reported use of
acceptance and putting into perspective, were observed for the clinical group.
The CER strategies in the clinical group, which differentiated it from the non
clinical group, accounted for 23.9% of the variance, after controlling for the
non-dominant variables. CONCLUSION: The implications of certain CER strategies
may be a useful target for prevention and intervention of psychological distress
on patients with gynecologic cancer.
PMID- 28697660
TI - Neuroprotective effects of a biodegradable poly(lactic-co-glycolic acid)
ginsenoside Rg3 nanoformulation: a potential nanotherapy for Alzheimer's disease?
AB - It is well established that overproduction and accumulation of the beta-amyloid
(Abeta) peptide 1-42 (Abeta(1-42)) is a trigger of the pathological cascade in
Alzheimer's disease (AD) that manifests as cognitive impairment. Ginsenoside Rg3
is an important constituent of ginseng, plays an essential role in memory and
improved cognition, and is known to produce antioxidant effects via the reduction
of free radicals. Therefore, ginsenoside Rg3 may be a promising candidate as a
neuroprotective agent for the treatment of AD. A novel nanotherapeutic strategy
that enhances delivery of ginsenosides to the brain by increasing its transport
across the blood brain barrier (BBB) would facilitate neuroprotection and limit
the accumulation of Abeta plaques and subsequent neurodegeneration. In this
current study, we formulated and characterised biodegradable poly(lactic-co
glycolic acid) (PLGA) nanoparticles (NPs) that encapsulate ginsenoside Rg3 and
Thioflavin T, an Abeta diagnostic; examine its neuroprotective effects;
investigate key mechanisms that may underlie its neuroprotective effects; and
evaluate its ability to cross the BBB using an in vitro BBB model. Our PLGA-Rg3
NPs offers an exciting new theranostic material capable of encapsulating natural
nutraceuticals for the detection and treatment of AD. In addition, this
nanotechnology strategy can be adapted to treat other neurological diseases,
utilising many natural therapeutic agents which are limited by their solubility
and/or poor pharmacokinetics.
PMID- 28697662
TI - Development of a Loop-Mediated Isothermal Amplification Assay for the Detection
of Dickeya spp.
AB - Dickeya and Pectobacterium spp. are responsible for soft-rotting diseases of
several plant species, some with overlapping host range. On potato, symptoms
caused by these pathogens cannot be clearly differentiated. Disease results in
the downgrading and rejection of potato seed, thus requiring additional
phytosanitary restrictions across Northern Europe and other parts of the world.
In an effort to provide a more timely and accurate diagnostic to distinguish
these two groups of pathogens, a method for detecting Dickeya spp. using loop
mediated isothermal amplification (LAMP) was developed. The LAMP assay can be
used to test crude extracts prepared directly from symptomatic lesions. The
entire test can be completed in less than 30 min, making it faster than the
current diagnostic standard, the pelADE conventional polymerase chain reaction.
Additionally, the LAMP assay was able to detect Dickeya DNA in samples spiked
with varying amounts of Pectobacterium DNA, thus demonstrating the highly
specific and sensitive nature of the assay, which can be applied on survey
samples with mixed soft-rotting bacterial populations.
PMID- 28697661
TI - Safety of a proteoliposome from Neisseria meningitides as adjuvant for a house
dust mite allergy vaccine.
AB - The proteoliposome (PL) of Neisseria meningitidis serogroup B has been reported
as a safe and potent vaccine adjuvant, inducing a TH1-skewed response. The
present study describes a pre-clinical safety evaluation of an allergy
therapeutic vaccine candidate based on purified allergens from Dermatophagoides
siboney house dust mite and PL as adjuvant, both components adsorbed onto
aluminum hydroxide gel. Two separate studies of acute toxicity evaluation were
performed in mice and rabbits, and two repeat-dose studies were conducted in non
sensitized and allergen-sensitized Balb/c mice, respectively. The study in
sensitized mice intends to model a therapeutic setting. Aerosolized allergen
challenge was used in both settings to model natural respiratory exposure. In the
therapeutic setting, mice were administered with three doses containing 2 MUg
allergen at weekly intervals [subcutaneous route] and subsequently challenged
with aerosolized allergen for 6 consecutive days. Parameters of general toxicity
effects were assessed via measures of behavior, body weight, food and water
consumption, and macroscopic evaluation of organs. Histological examination of
organs and the injection site was performed. Potential immunotoxicity effects at
the systemic level were assessed by blood eosinophil counting and serum allergen
specific IgE by ELISA The vaccine did not produce general or functional toxic
effects of significance, at a dose up to 100 MUg allergen per kg body weight. An
expected local reaction at the injection site was observed, which could be
attributed mostly to the immunological effect of aluminum hydroxide. The models
implemented here suggest an acceptable safety profile of this vaccine for testing
in clinical trials of allergy immunotherapy.
PMID- 28697663
TI - The Point Mutation G461S in the MfCYP51 Gene is Associated with Tebuconazole
Resistance in Monilinia fructicola Populations in Brazil.
AB - The ascomycete Monilinia fructicola is the causal agent of brown rot of stone
fruit in Brazil, causing major pre- and postharvest losses. For many years, the
demethylation inhibitor (DMI) fungicide tebuconazole has been used as the most
effective active ingredient for controlling brown rot and, as a result, strains
of M. fructicola resistant to this ingredient have emerged in many Brazilian
states producing stone fruit. The aim of this study was to investigate the
mechanisms associated with the resistance of M. fructicola to DMI tebuconazole.
By sequencing the M. fructicola CYP51 (MfCYP51) gene, encoding the azole target
sterol 14alpha-demethylase, a mutation was identified at the nucleotide position
1,492, causing the amino acid substitution from glycine to serine at the codon
position 461, associated with reduced tebuconazole sensitivity. In addition, it
was observed that MfCYP51 gene expression could play a secondary role in DMI
fungicide resistance of M. fructicola strains in Brazil. However, for the
specific isolate found to exhibit elevated expression levels of MfCYP51, no
insertions that would trigger gene expression were found. Based on the point
mutation associated with tebuconazole resistance, an allele-specific polymerase
chain reaction method was developed to quickly identify resistant genotypes
within the Brazilian population. This is the first report determining molecular
mechanisms for DMI resistance identification for M. fructicola isolates from
Brazil. This information provides an important advancement for risk assessment of
DMI fungicides used to manage brown rot of stone fruit.
PMID- 28697664
TI - Compare the safety and efficacy of endoscopic third ventriculostomy and
ventriculoperitoneal shunt placement in infants and children with hydrocephalus:
a systematic review and meta-analysis.
AB - PURPOSE: Endoscopic third ventriculostomy (ETV) and ventriculoperitoneal shunt
placement are two surgical options used for treatment of non-communicating
hydrocephalus. The purpose of this study was to compare the efficiency and safety
of these techniques in pediatric patients. MATERIALS AND METHODS: An extensive
literature review regarding the clinical outcome, safety, and efficiency of ETV
and shunting in treatment of hydrocephalus was conducted in Medline, PubMed,
Cochrane, and Google Scholar databases up to November 27th, 2015. Patient
demographics, ETV and shunting success and failure rates were extracted. RESULTS:
A total of 7 two-arm studies were included for quantitative analysis and 25
single-arm studies were included for systematic review. The two-arm studies
recruited a total of 6995 patients: 1046 in the ETV group and 5949 in the shunt
group. The pooled results showed that the 1 year success rate of ETV and shunt
placement procedure were similar (pooled RR = 0.870, 95% CI = 0.680 to 1.112, P =
0.266). The failure rate in the ETV treatment group was 0.9 times higher than in
the shunt group; however, the results did not reach statistical significance
(pooled RR = 0.893, 95% CI = 0.576 to 1.383, P = 0.611). CONCLUSIONS: Both ETV
and shunts are associated with similar 1 year success and failure rates.
Therefore, there are no current indications to recommend one mode of treatment
over the other. Future studies designed to assess the effectiveness of ETV and
shunt procedures depending on patient's age and etiology are warranted.
PMID- 28697665
TI - Variant Gene Expression and Antigenic Variation by Malaria Parasites.
AB - Malaria is a significant threat throughout the developing world. Among the most
fascinating aspects of the protozoan parasites responsible for this disease are
the methods they employ to avoid the immune system and perpetuate chronic
infections. Key among these is antigenic variation: By systematically altering
antigens that are displayed to the host's immune system, the parasite renders the
adaptive immune response ineffective. For Plasmodium falciparum, the species
responsible for the most severe form of human malaria, this process involves a
complicated molecular mechanism that results in continuously changing patterns of
variant-antigen-encoding gene expression. Although many features of this process
remain obscure, significant progress has been made in recent years to decipher
various molecular aspects of the regulatory cascade that causes chronic
infection.
PMID- 28697666
TI - Bacterial Cell Division: Nonmodels Poised to Take the Spotlight.
AB - The last three decades have witnessed an explosion of discoveries about the
mechanistic details of binary fission in model bacteria such as Escherichia coli,
Bacillus subtilis, and Caulobacter crescentus. This was made possible not only by
advances in microscopy that helped answer questions about cell biology but also
by clever genetic manipulations that directly and easily tested specific
hypotheses. More recently, research using understudied organisms, or nonmodel
systems, has revealed several alternate mechanistic strategies that bacteria use
to divide and propagate. In this review, we highlight new findings and compare
these strategies to cell division mechanisms elucidated in model organisms.
PMID- 28697667
TI - Evolutionary Trajectories to Antibiotic Resistance.
AB - The ability to predict the evolutionary trajectories of antibiotic resistance
would be of great value in tailoring dosing regimens of antibiotics so as to
maximize the duration of their usefulness. Useful prediction of resistance
evolution requires information about (a) the mutation supply rate, (b) the level
of resistance conferred by the resistance mechanism, (c) the fitness of the
antibiotic-resistant mutant bacteria as a function of drug concentration, and (d)
the strength of selective pressures. In addition, processes including epistatic
interactions and compensatory evolution, coselection of drug resistances, and
population bottlenecks and clonal interference can strongly influence resistance
evolution and thereby complicate attempts at prediction. Currently, the very
limited quantitative data on most of these parameters severely limit attempts to
accurately predict trajectories of resistance evolution.
PMID- 28697668
TI - Syntrophy Goes Electric: Direct Interspecies Electron Transfer.
AB - Direct interspecies electron transfer (DIET) has biogeochemical significance, and
practical applications that rely on DIET or DIET-based aspects of microbial
physiology are growing. Mechanisms for DIET have primarily been studied in
defined cocultures in which Geobacter species are one of the DIET partners.
Electrically conductive pili (e-pili) can be an important electrical conduit for
DIET. However, there may be instances in which electrical contacts are made
between electron transport proteins associated with the outer membranes of the
partners. Alternatively, DIET partners can plug into conductive carbon materials,
such as granular activated carbon, carbon cloth, and biochar, for long-range
electron exchange without the need for e-pili. Magnetite promotes DIET, possibly
by acting as a substitute for outer-surface c-type cytochromes. DIET is the
primary mode of interspecies electron exchange in some anaerobic digesters
converting wastes to methane. Promoting DIET with conductive materials shows
promise for stabilizing and accelerating methane production in digesters,
permitting higher organic loading rates. Various lines of evidence suggest that
DIET is important in terrestrial wetlands, which are an important source of
atmospheric methane. DIET may also have a role in anaerobic methane oxidation
coupled to sulfate reduction, an important control on methane releases. The
finding that DIET can serve as the source of electrons for anaerobic
photosynthesis further broadens its potential environmental significance.
Microorganisms capable of DIET are good catalysts for several bioelectrochemical
technologies and e-pili are a promising renewable source of electronic materials.
The study of DIET is in its early stages, and additional investigation is
required to better understand the diversity of microorganisms that are capable of
DIET, the importance of DIET to carbon and electron flow in anaerobic
environments, and the biochemistry and physiology of DIET.
PMID- 28697670
TI - Germination of Spores of the Orders Bacillales and Clostridiales.
AB - Dormant Bacillales and Clostridiales spores begin to grow when small molecules
(germinants) trigger germination, potentially leading to food spoilage or
disease. Germination-specific proteins sense germinants, transport small
molecules, and hydrolyze specific bonds in cortex peptidoglycan and specific
proteins. Major events in germination include (a) germinant sensing; (b)
commitment to germinate; (c) release of spores' depot of dipicolinic acid (DPA);
(d) hydrolysis of spores' peptidoglycan cortex; and (e) spore core swelling and
water uptake, cell wall peptidoglycan remodeling, and restoration of core protein
and inner spore membrane lipid mobility. Germination is similar between
Bacillales and Clostridiales, but some species differ in how germinants are
sensed and how cortex hydrolysis and DPA release are triggered. Despite detailed
knowledge of the proteins and signal transduction pathways involved in
germination, precisely what some germination proteins do and how they do it
remain unclear.
PMID- 28697669
TI - Rewriting the Genetic Code.
AB - The genetic code-the language used by cells to translate their genomes into
proteins that perform many cellular functions-is highly conserved throughout
natural life. Rewriting the genetic code could lead to new biological functions
such as expanding protein chemistries with noncanonical amino acids (ncAAs) and
genetically isolating synthetic organisms from natural organisms and viruses. It
has long been possible to transiently produce proteins bearing ncAAs, but
stabilizing an expanded genetic code for sustained function in vivo requires an
integrated approach: creating recoded genomes and introducing new translation
machinery that function together without compromising viability or clashing with
endogenous pathways. In this review, we discuss design considerations and
technologies for expanding the genetic code. The knowledge obtained by rewriting
the genetic code will deepen our understanding of how genomes are designed and
how the canonical genetic code evolved.
PMID- 28697671
TI - Bacterial Membranes: Structure, Domains, and Function.
AB - The bacterial cytoplasmic membrane is composed of roughly equal proportions of
lipids and proteins. The main lipid components are phospholipids, which vary in
acyl chain length, saturation, and branching and carry head groups that vary in
size and charge. Phospholipid variants determine membrane properties such as
fluidity and charge that in turn modulate interactions with membrane-associated
proteins. We summarize recent advances in understanding bacterial membrane
structure and function, focusing particularly on the possible existence and
significance of specialized membrane domains. We review the role of membrane
curvature as a spatial cue for recruitment and regulation of proteins involved in
morphogenic functions, especially elongation and division. Finally, we examine
the role of the membrane, especially regulation of synthesis and fluid
properties, in the life cycle of cell wall-deficient L-form bacteria.
PMID- 28697672
TI - Projectors, associators, visual imagery, and the time course of visual processing
in grapheme-color synesthesia.
AB - In grapheme-color synesthesia, seeing particular letters or numbers evokes the
experience of specific colors. We investigate the brain's real-time processing of
words in this population by recording event-related brain potentials (ERPs) from
15 grapheme-color synesthetes and 15 controls as they judged the validity of word
pairs ('yellow banana' vs. 'blue banana') presented under high and low visual
contrast. Low contrast words elicited delayed P1/N170 visual ERP components in
both groups, relative to high contrast. When color concepts were conveyed to
synesthetes by individually tailored achromatic grapheme strings ('55555
banana'), visual contrast effects were like those in color words: P1/N170
components were delayed but unchanged in amplitude. When controls saw equivalent
colored grapheme strings, visual contrast modulated P1/N170 amplitude but not
latency. Color induction in synesthetes thus differs from color perception in
controls. Independent from experimental effects, all orthographic stimuli
elicited larger N170 and P2 in synesthetes than controls. While P2 (150-250ms)
enhancement was similar in all synesthetes, N170 (130-210ms) amplitude varied
with individual differences in synesthesia and visual imagery. Results suggest
immediate cross-activation in visual areas processing color and shape is most
pronounced in so-called projector synesthetes whose concurrent colors are
experienced as originating in external space.
PMID- 28697673
TI - Visual cortex activation predicts visual preference: Evidence from Britain and
Egypt.
AB - The term "Perceptual goodness" refers to the strength, obviousness, or salience
of a visual configuration. Recent work has found strong agreement between
theoretical, neural, and behavioural measures of perceptual goodness across a
wide range of different symmetrical visual patterns. We used these pattern types
again to explore the relationship between perceptual goodness and aesthetic
preference. A group of 50 U.K. participants rated the patterns on a 0 to 100
scale. Preference ratings positively correlated with four overlapping measures of
perceptual goodness. We then replicated this finding in Egypt, suggesting that
our results reflect universal aspects of human preference. The third experiment
provided consistent results with a different stimulus set. We conclude that
symmetry is an aesthetic primitive that is attractive because of the way it is
processed by the visual system.
PMID- 28697674
TI - Training adults with acquired brain injury how to help-seek when wayfinding: an
understudied critical life skill.
AB - The objective of this study was to investigate the efficacy of a group treatment
protocol called NICE (Noticing you have a problem, Identifying the information
you need for help, Compensatory strategies, Evaluating progress) to train help
seeking when wayfinding for individuals with acquired brain injury (ABI). Seven
participants completed the NICE group treatment in an outpatient rehabilitation
department at a university medical centre. A single subject multiple baseline
design was employed to evaluate the efficacy of the NICE group treatment. The
Social Behaviour Rating Scale and the Executive Function Route-Finding Task-
Revised were repeated measures used to evaluate potential changes in help-seeking
and wayfinding. Secondary outcome measures included pre- and post-treatment
evaluation of social problem solving and social cognition. Results revealed that
all participants improved on measures of help-seeking and wayfinding. Patterns of
improvement and implications for rehabilitation are discussed. This is the first
experimental study to evaluate the treatment of help-seeking behaviours and
discuss its application to wayfinding in adults with ABI. Preliminary evidence
supports further investigation of the NICE group treatment protocol.
PMID- 28697675
TI - Malignant Mixed Epithelial and Stromal Tumor of the Kidney With 2 Simultaneous
Renal Carcinomas in a Male Patient: Case Report and Review of the Literature.
AB - The majority of mixed epithelial and stromal tumors (MEST) of the kidney are
benign entities found in female patients. Malignant MEST of the kidney is an
extremely rare entity that often behaves clinically similar to an
undifferentiated sarcoma. We report a case of a malignant MEST with synchronous
papillary and clear cell renal cell carcinomas (RCCs) in a 61-year-old Caucasian
man who presented with an incidental finding of a left renal mass on workup for
back pain. The patient underwent a left radical nephrectomy, with histopathology
confirming a malignant MEST, intimately associated papillary RCC, and separate
adjacent focus of clear cell RCC.
PMID- 28697676
TI - A comparison trial between three treatment modalities for the management of
myofascial pain of jaw muscles: A preliminary study.
AB - OBJECTIVES: To compare three treatment modalities for the management of
myofascial pain of jaw muscles. METHODS: Thirty (N = 30) patients with low pain
related impairment were randomly assigned to receive laser therapy (LST), oral
appliance therapy (OA), or counseling (CSL). Visual Analog Scale (VAS) pain
levels and the Muscular Index (MI) of the Craniomandibular Index were the outcome
variables, which were assessed at baseline, at three weeks, three months, and six
months. RESULTS: At six months, improvement in the MI was maintained both in the
LST (p = .025) and OA groups (p < .001). As for VAS values, positive changes were
still shown for LST (p = .001), and were also shown for the OA (p = .002) and CSL
groups (p = .048). CONCLUSIONS: Despite differences in the short-term
effectiveness of LST and OA, with respect to CSL alone, all three treatment
groups improved at six months. This suggests that active treatments should be
directed to maximize the positive changes in the short-term period.
PMID- 28697677
TI - Material Perception.
AB - Under typical viewing conditions, human observers effortlessly recognize
materials and infer their physical, functional, and multisensory properties at a
glance. Without touching materials, we can usually tell whether they would feel
hard or soft, rough or smooth, wet or dry. We have vivid visual intuitions about
how deformable materials like liquids or textiles respond to external forces and
how surfaces like chrome, wax, or leather change appearance when formed into
different shapes or viewed under different lighting. These achievements are
impressive because the retinal image results from complex optical interactions
between lighting, shape, and material, which cannot easily be disentangled. Here
I argue that because of the diversity, mutability, and complexity of materials,
they pose enormous challenges to vision science: What is material appearance, and
how do we measure it? How are material properties estimated and represented?
Resolving these questions causes us to scrutinize the basic assumptions of mid
level vision.
PMID- 28697678
TI - EK (DLEK, DSEK, DMEK): New Frontier in Cornea Surgery.
AB - Endothelial keratoplasty (EK) has revolutionized treatment of corneal endothelial
dysfunction. Compared with penetrating keratoplasty (PK), EK provides faster and
more reliable visual rehabilitation while maintaining the eye's structural
integrity. The number of EK procedures is growing annually and surpassed PK in
the United States in 2012. The most widely used iteration, Descemet stripping
endothelial keratoplasty (DSEK), implants healthy donor endothelium, Descemet
membrane, and posterior stroma. Descemet membrane endothelial keratoplasty (DMEK)
eliminates the donor stromal layer. Although more surgically challenging than
DSEK, DMEK provides even faster visual rehabilitation and reduced risk of
immunologic rejection, so its use is growing. Potential future alternatives to EK
that could help address the unmet demand for donor corneas include removing
central guttae and regenerating a central endothelial cell layer from healthy
peripheral cells in patients with Fuchs' dystrophy or injecting cultured human
corneal endothelial cells to rehabilitate eyes without residual healthy
endothelium.
PMID- 28697679
TI - Increased synthetic drug abuse and trends in HIV and syphilis prevalence among
female drug users from 2010-2014 from Beijing, China.
AB - The objective of this study was to monitor the trend of addiction drug use and
its relationship with sexually transmitted infections (STIs) among female drug
users (FDUs). Serial cross-sectional surveys were conducted during 2010-2014
among FDUs in Beijing to collect information on addiction drug usage, sexual
behaviors, and STI prevalence. Characteristics were analyzed and compared between
traditional and synthetic drug users among FDUs by logistic regression method. A
total of 3859 FDUs were surveyed during 2010-2014, with the median age being 32.7
years old. The proportion of synthetic drug users among FDUs increased from 43.7%
in 2010 to 70.7% in 2014. Compared with traditional drug users, synthetic drug
users were younger (P < 0.001), lacked education (P < 0.001), were unmarried (P <
0.001), and were non-local residents (P < 0.001). No significant difference was
found with condom usage during sexual activity between traditional and synthetic
drug FDUs. However, the engagement of commercial sexual activities (P < 0.001)
and syphilis prevalence (P < 0.001) among synthetic drug users were significantly
higher than traditional drug users. Synthetic drug abuse appears to be correlated
with commercial sex behavior and higher syphilis prevalence among FDUs. Tailored
strategies on health education to curb the prevalence of synthetic drug abuse are
urgently needed in Beijing.
PMID- 28697680
TI - T-2 toxin induces apoptosis via the Bax-dependent caspase-3 activation in mouse
primary Leydig cells.
AB - To explore the toxic effect of T-2 toxin on mouse Leydig cells and its underlying
molecular mechanisms, we isolated Leydig cells from mature mice, set-up Leydig
cells culture, treated cells with T-2 toxin, evaluated cell proliferation,
detected the caspase-3 activity, mitochondrial activity and apoptosis rate, and
measured the mRNA levels of Bcl-2, Bax, PARP and caspase-3. T-2 toxin inhibited
cell proliferation at concentrations higher than 10-9 M or time more than 12 h, T
2 toxin also decreased Bcl-2 expression at the mRNA levels and mitochondrial
activity at concentrations higher than 10-9 M. While, T-2 toxin increased the
mRNA expressions of Bax and PARP at concentrations higher than 10-8 M and 10-9 M,
respectively, triggered mitochondria-mediated apoptosis, activated downstream
caspase-3, and then increased caspase-3 at the activity and mRNA levels at
concentrations higher than 10-9 M. These data showed that T-2 toxin appears to
activate specific intracellular death-related pathways leading to Bax-dependent
caspase-3 activation and the induction of apoptosis in Leydig cells.
PMID- 28697681
TI - A particularly complex case of matricide by means of plastic bag suffocation:
Case report.
AB - A rare case of homicide with plastic bag suffocation is presented in which
forensic genetic investigations were carried out on the inner surface of a
plastic bag placed over the head of an elderly woman, bedridden after a stroke.
The results obtained suggested that she had been murdered and hinted at the
perpetrator of the crime. In fact, it emerged that biological traces left by the
victim matched those of her principal caregiver, her psychotic daughter, who
later confessed to the crime. The old woman also had a son affected by a serious
illness, whose genetic profile was found on the same bag. In a later interview,
he stated that his sister had tried to kill him too, thus confirming the genetic
findings and allowing the investigators to hypothesise that the daughter had used
the same means to try to kill him. Based on these results, the usefulness of
forensic genetic testing when investigating complex plastic bag suffocation
deaths is highlighted. This peculiar case deserves interest, since no murder of
this kind has ever been reported in the Italian forensic literature.
PMID- 28697682
TI - A comfort assessment of existing cervical orthoses.
AB - PURPOSE: Identify location and intensity of discomfort experienced by healthy
participants wearing cervical orthoses. METHOD: Convenience sample of 34 healthy
participants wore Stro II, Philadelphia, Headmaster, and AspenVista(r) cervical
orthoses for four-hour periods. Participants reported discomfort level (scale 0
6) and location. RESULTS: Participants reported mean discomfort for all orthoses
over the four-hour test between 'a little discomfort' and 'very uncomfortable'
(mean discomfort score = 1.64, SD = 1.50). Seven participants prematurely stopped
tests due to pain and six reported maximum discomfort scores. Significant linear
increase in discomfort with duration of wear was found for all orthoses.
Significantly less discomfort was reported with Stro II than Headmaster and
Philadelphia. Age correlated with greater perceived discomfort. Orthoses differed
in the location discomfort was experienced. CONCLUSION: Existing cervical
orthoses cause discomfort influenced by design and duration of wear with
orthoses' design the more significant factor. This work informed the design of a
new orthosis and future orthoses developments. Practitioner Summary: The purpose
of this study was to gain greater knowledge about the discomfort caused by
wearing of existing neck orthoses in order to inform the design and development
of a new neck orthosis. This study gathers empirical data from a surrogate
population and concludes that orthosis design is more influential than the
duration of wear.
PMID- 28697683
TI - Metastatic Sclerosing Epithelioid Fibrosarcoma in Bone Marrow.
AB - Sclerosing epithelioid fibrosarcoma (SEF) is an aggressive neoplasm thought to be
related to low-grade fibromyxoid sarcoma, which typically occurs in middle-aged
adults in the deep soft tissues of the lower extremities and trunk. It comprises
nests and cords of relatively uniform epithelioid polygonal cells with clear or
eosinophilic cytoplasm in densely sclerotic stroma, and it is typically
associated with EWSR1 gene rearrangements, and most commonly EWSR1-CREB3L1
fusions. As primary SEF can arise in bone, and bone is also a common metastatic
site for SEF, its recognition at this site is important. We illustrate bone
marrow showing diffuse infiltration by SEF and highlight the potential for
confusion with a range of neoplasms such as carcinoma, hematolymphoid neoplasms,
and other sarcomas.
PMID- 28697684
TI - What is the accuracy of an early third trimester sonogram for identifying LGA
infants born to GDM patients diagnosed with the one-step approach?
AB - PURPOSE: The one-step approach for screening of GDM will increase the incidence 2
to 3-fold. These larger cohorts may need to target high-morbidity subsets to be
cost-effective. We asked whether ultrasound could stratify the GDM patients with
the highest risk for a large for gestational age (LGA) infant. MATERIALS AND
METHODS: A retrospective analysis was performed on 413 GDM patients diagnosed
using the one-step approach. Ultrasound data from 28 weeks 0 day to 34 weeks 6
days was studied. The abdominal circumference (AC) and EFW at thresholds between
70 and 95% were examined for their prognostic utility. The primary outcome was an
LGA infant. RESULTS: Both the AC and EFW at all gestational ages were predictive
of a LGA infant. The AC and EFW at 28-32 weeks 6 days using a threshold of >=70%
showed the following test characteristics: sensitivity (73 versus 66%),
specificity (61 versus 77%), positive predictive value (PPV) (30 versus 40%), and
negative predictive value (NPV) (91 versus 91%). The specificity of the EFW was
significantly higher than the AC (p < .001). CONCLUSION: Among GDM patients
diagnosed using the one-step approach, an elevated AC and EFW in the early third
trimester are predictive of a LGA infant. This is a possible cost-effective way
to stratify the one-step GDM pregnancies at highest risk for neonatal morbidity.
PMID- 28697685
TI - Interruptions and multitasking in surgery: a multicentre observational study of
the daily work patterns of doctors and nurses.
AB - The aim of this study was to obtain baseline data on doctors' and nurses' work
activities and rates of interruptions and multitasking to improve work
organisation and processes. Data were collected in six surgical units with the
WOMBAT (Work Observation Method by Activity Timing) tool. Results show that
doctors and nurses received approximately 13 interruptions per hour, or one
interruption every 4.5 min. Compared to doctors, nurses were more prone to
interruptions in most activities, while doctors performed multitasking (33.47% of
their time, 95% CI 31.84-35.17%) more than nurses (15.23%, 95% CI 14.24-16.25%).
Overall, the time dedicated to patient care is relatively limited for both
professions (37.21%, 95% CI 34.95-39.60% for doctors, 27.22%, 95% CI 25.18-29.60%
for nurses) compared to the time spent for registration of data and professional
communication, that accounts for two-thirds of doctors' time and nearly half of
nurses' time. Further investigation is needed on strategies to manage job demands
and professional communications. Practitioner Summary: This study offers further
findings on the characteristics and frequency of multitasking and interruptions
in surgery, with a comparison of how they affect doctors and nurses. Further
investigation is needed to improve the management of job demands and
communications according to the results.
PMID- 28697686
TI - Cytomegalovirus antigenemia and end-organ disease in Japanese patients treated
with bendamustine.
PMID- 28697687
TI - The fractions SNARC revisited: Processing fractions on a consistent mental number
line.
AB - The ability to understand fractions is key to establishing a solid foundation in
mathematics, yet children and adults struggle to comprehend them. Previous
studies have suggested that these struggles emerge because people fail to process
fraction magnitude holistically on the mental number line (MNL), focusing instead
on fraction components. Subsequent studies have produced evidence for default
holistic processing but examined only magnitude processing, not spatial
representations. We explored the spatial representations of fractions on the MNL
in a series of three experiments. Experiment 1 replicated Bonato et al.; 30 naive
undergraduates compared unit fractions (1/1-1/9) to 1/5, resulting in a reverse
SNARC (Spatial-Numerical Association of Response Codes) effect. Experiment 2
countered potential strategic biases induced by the limited set of fractions used
by Bonato et al. by expanding the stimulus set to include all irreducible, single
digit proper fractions and asked participants to compare them against 1/2. We
observed a classic SNARC effect, completely reversing the pattern from Experiment
1. Together, Experiments 1 and 2 demonstrate that stimulus properties
dramatically impact spatial representations of fractions. In Experiment 3, we
demonstrated within-subjects reliability of the SNARC effect across both a
fractions and whole number comparison task. Our results suggest that adults can
indeed process fraction magnitudes holistically, and that their spatial
representations occur on a consistent MNL for both whole numbers and fractions.
PMID- 28697688
TI - Plumbago auriculata leaf extract-mediated AgNPs and its activities as
antioxidant, anti-TB and dye degrading agents.
AB - In the present work, silver nanoparticles have been biosynthesized by utilizing
the alcoholic extract of Plumbago auriculata. The optimization of reaction
conditions was carried out by monitoring the reactions with the help of UV
Visible absorption spectroscopy. The characterization of AgNP was carried out by
infrared spectroscopy, transmission electron microscopy and X-Ray diffraction
(XRD) studies. The biogenic AgNPs were tested against Mycobacterium tuberculosis
using Microplate Almar Blue assay (MABA) and their antioxidant activity was also
evaluated. The silver nanoparticles were also assessed for their reducing
activity against organic dyes. The AgNPs were spherical in shape with size
ranging from 15 to 45 nm with face centered cubic geometry as revealed by XRD
analysis. The AgNPs possessed good antitubercular activity with MIC value of 1.6
MUg/ml and these also exhibited promising antioxidant activity with IC50 value of
28.2. Furthermore, AgNPs also reduced congo red within 2 h and malachite green
was degraded within 40 min. The present work demonstrated the utilization of P.
auriculata for biosynthesis of AgNP which could be a potential candidate for
antitubercular drug development and it could also be used as an antioxidant
agent. The application of AgNP in reducing agent can be further extended and
evaluated for purification of effluent water from textile industries.
PMID- 28697689
TI - Vitamin D Treatment in Patients with Hashimoto's Thyroiditis may Decrease the
Development of Hypothyroidism.
AB - The relationship between Hashimoto's thyroiditis and vitamin D has been
demonstrated in several studies. The aim of the present study was to evaluate
vitamin D concentrations in patients with Hashimoto's thyroiditis, the effect of
vitamin D therapy on the course of disease, and to determine changes in thyroid
autoantibody status and cardiovascular risk after vitamin D therapy. We included
75 patients with Hashimoto's thyroiditis and 43 healthy individuals. Vitamin D
deficiency is defined as a 25-hydroxy vitamin D (25(OH)D3) concentration less
than 20ng/mL. Vitamin D deficient patients were given 50.000 units of 25(OH)D3
weekly for eight weeks in accordance with the Endocrine Society guidelines. All
evaluations were repeated after 2 months of treatment. Patients with Hashimoto's
thyroiditis had significantly lower vitamin D concentrations compared with the
controls (9.37+/-0.69 ng/mL vs 11.95+/-1.01 ng/mL, p < 0.05, respectively).
Thyroid autoantibodies were significantly decreased by vitamin D replacement
treatment in patients with euthyroid Hashimoto's thyroiditis. Also, HDL
cholesterol concentrations improved in the euthyroid Hashimoto group after
treatment. The mean free thyroxine (fT4) concentrations were 0.89+/-0.02 ng/dL in
patients with Hashimoto's thyroiditis and 1.07+/-0.03 ng/dL in the healthy
control group (p < 0.001). The mean thyroid volumes were 7.71+/-0.44 mL in
patients with Hashimoto's thyroiditis and 5.46+/-0.63 mL in the healthy control
group (p < 0.01). Vitamin D deficiency is frequent in Hashimoto's thyroiditis and
treatment of patients with this condition with Vitamin D may slow down the course
of development of hypothyroidism and also decrease cardiovascular risks in these
patients. Vitamin D measurement and replacement may be critical in these
patients.
PMID- 28697690
TI - Try and try again: Post-error boost of an implicit measure of agency.
AB - The sense of agency refers to the feeling that we control our actions and,
through them, effects in the outside world. Reinforcement learning provides an
important theoretical framework for understanding why people choose to make
particular actions. Few previous studies have considered how reinforcement and
learning might influence the subjective experience of agency over actions and
outcomes. In two experiments, participants chose between two action alternatives,
which differed in reward probability. Occasional reversals of action-reward
mapping required participants to monitor outcomes and adjust action selection
processing accordingly. We measured shifts in the perceived times of actions and
subsequent outcomes ('intentional binding') as an implicit proxy for sense of
agency. In the first experiment, negative outcomes showed stronger binding
towards the preceding action, compared to positive outcomes. Furthermore,
negative outcomes were followed by increased binding of actions towards their
outcome on the following trial. Experiment 2 replicated this post-error boost in
action binding and showed that it only occurred when people could learn from
their errors to improve action choices. We modelled the post-error boost using an
established quantitative model of reinforcement learning. The post-error boost in
action binding correlated positively with participants' tendency to learn more
from negative outcomes than from positive outcomes. Our results suggest a novel
relation between sense of agency and reinforcement learning, in which sense of
agency is increased when negative outcomes trigger adaptive changes in subsequent
action selection processing.
PMID- 28697691
TI - The relationship between mechanical stiffness and athletic performance markers in
sub-elite footballers.
AB - This study investigated the relationship between several measures of lower-body
stiffness and physical performance variables in 22 sub-elite male football
players (mean +/- SD; 21.9 +/- 1.5 yr; 1.79 +/- 0.06 m; 72.2 +/- 7.2 kg). The
participants were assessed for individual muscle stiffness of the Rectus Femoris
(RF), Biceps Femoris (BF) and Medial Gastrocnemius (MG) muscles and vertical
stiffness (Kvert) was also assessed assessed running acceleration, maximal sprint
speed, agility, vertical jumping and muscular strength. Pearson's correlations
quantified the relationships and participants were also separated into relatively
stiff (SG) and compliant groups (CG) for each variable. When ranked by Kvert the
SG exhibited superior performance during sprinting, agility, jumping and strength
(p <= 0.05) and when ranked by RF stiffness, SG exhibited superior sprint,
agility and drop jump performance (p <= 0.05), while MG and BF stiffness were not
related to performance. Higher stiffness appears to be beneficial to athletic
performance for football players and therefore it may be beneficial for
practitioners working with athletes that are required to perform dynamic
activities to consider the contribution of stiffness to athletic performance.
PMID- 28697692
TI - Primary Intra-aortic Epstein-Barr Virus-Positive Large B-Cell Lymphoma Presenting
as Aortic Mural Thrombosis: An Entity Distinct From Intravascular Large B-Cell
Lymphoma.
AB - Intravascular selective growth of neoplastic B lymphocytes is a characteristic
finding of intravascular large B-cell lymphoma (IVLBCL). However, because
neoplastic B cells of IVLBCL grow merely in the lumina of capillaries or small
vessels, primary IVLBCL of the great vessels is considered exceptional. To our
knowledge, only 2 primary B-cell lymphomas in the lumina of the vena cava have
been reported. However, there has been no report of primary B-cell lymphoma with
intra-aortic growth. We describe a novel manifestation of primary Epstein-Barr
virus-positive large B-cell lymphoma mainly affecting the lumina of the aorta and
its major branches in a 76-year-old man. He had a long-term fever that was
refractory to antibiotics and aortic mural thrombosis with visceral embolization.
Because he had no detectable mass suggesting a malignancy, it was difficult to
diagnose while he was alive. He died without anticancer treatment, and the
confirmed diagnosis was made at autopsy.
PMID- 28697693
TI - Pivotal Study of a Next-Generation Balloon-Expandable Stent-Graft for Treatment
of Iliac Occlusive Disease.
AB - PURPOSE: To evaluate the safety and efficacy of a next-generation balloon
expandable stent-graft for the treatment of arterial occlusive disease in
patients with de novo or restenotic lesions in the common and/or external iliac
arteries. METHODS: A prospective, multicenter, single-arm safety and efficacy
study ( ClinicalTrials.gov identifier: NCT02080871) of the VBX Stent Graft for
treatment of de novo or restenotic lesions in the iliac arteries was conducted
under an Investigational Device Exemption at 26 US sites and 1 New Zealand
center. The study eligibility criteria were established with the aim of enrolling
more "real-world" patients compared with previous iliac stent studies supporting
Food and Drug Administration approval. The study enrolled 134 patients (mean age
66+/-9.5 years; 79 men) with 213 iliac lesions. Three-quarters of the population
(101, 75.4%) had Rutherford category 3 ischemia, and 43 (32.1%) patients
presented with TASC II C/D lesions. The primary endpoint was a composite of
device- or procedure-related death within 30 days, myocardial infarction within
30 days, target lesion revascularization (TLR) within 9 months, and amputation
above the metatarsals in the treated leg within 9 months. RESULTS: In all, 234
devices were implanted in 213 lesions with 100% technical success; 57 (42.5%)
patients received kissing stents at the aortic bifurcation. No devices exhibited
a discernable change in length after final deployment as determined by
independent core laboratory quantitative angiographic analysis. At 9 months, 3
(2.3%) of 132 patients (1 lost to follow-up, 1 unrelated death) experienced a
major adverse event (3 TLRs) related to the primary endpoint. At 9 months, there
were no device-related serious adverse events or unanticipated adverse device
effects. CONCLUSION: The next-generation balloon-expandable stent-graft
demonstrated notable 9-month safety and efficacy in treating iliac occlusive
disease in patients reflecting common clinical practice.
PMID- 28697694
TI - Midterm Outcomes From a Pilot Study of Percutaneous Deep Vein Arterialization for
the Treatment of No-Option Critical Limb Ischemia.
AB - PURPOSE: To report the initial clinical experience with percutaneous deep vein
arterialization (PDVA) to treat critical limb ischemia (CLI) via the creation of
an arteriovenous fistula. METHODS: Seven patients (median age 85 years; 5 women)
with CLI and no traditional endovascular or surgical revascularization options
(no-option CLI) were recruited in a pilot study to determine the safety of PDVA.
All patients were diabetic; 4 had Rutherford category 6 ischemia. Six were
classified at high risk of amputation based on the Society for Vascular Surgery
WIfI (wound, ischemia, and foot infection) classification. The primary safety
endpoints were major adverse limb events and major adverse coronary events
through 30 days and serious adverse events through 6 months. Secondary objectives
included clinical efficacy based on outcome measures including thermal
measurement, transcutaneous partial pressure of oxygen (TcPO2), clinical
improvement at 6 months, and wound healing. RESULTS: The primary safety endpoints
were achieved in 100% of patients, with no deaths, above-the-ankle amputations,
or major reinterventions at 30 days. The technical success rate was 100%. Two
myocardial infarctions occurred within 30 days, each with minor clinical
consequences. All patients demonstrated symptomatic improvement with formation of
granulation tissue, resolution of rest pain, or both. Complete wound healing was
achieved in 4 of 7 patients and 5 of 7 patients at 6 and 12 months, respectively,
with a median healing time of 4.6 months (95% confidence interval 84-192). Median
postprocedure peak TcPO2 was 61 mm Hg compared to a preprocedure level of 8 mm Hg
(p=0.046). At the time of wound healing, 4 of 5 of patients achieved TcPO2 levels
of >40 mm Hg. There were 2 major amputations, 1 above the knee after PDVA
thrombosis and 1 below the knee for infection. Three patients died of causes
unrelated to the procedure or study device at 6, 7, and 8 months, respectively.
Limb salvage was 71% at 12 months. CONCLUSION: PDVA is an innovative approach for
treating no-option CLI and represents an alternative option for the "desert
foot," potentially avoiding major amputation. Our results demonstrate its safety
and feasibility, with promising early clinical results in this small cohort.
PMID- 28697695
TI - Intonation and Pragmatic Enrichment: How Intonation Constrains Ad Hoc Scalar
Inferences.
AB - Pragmatic inferences require listeners to use alternatives to arrive at the
speaker's intended meaning. Previous research has shown that intonation interacts
with alternatives but not how it does so. We present two mouse tracking
experiments that test how pitch accents affect the processing of ad hoc scalar
implicatures in English. The first shows that L+H* accents facilitate
implicatures relative to H* accents. The second replicates this finding and
demonstrates that the facilitation is caused by early derivation of the
implicature in the L+H* condition. We attribute the effect to a link between L+H*
and pragmatic considerations, such as speaker knowledge effects, or the saliency
of alternatives relevant to the computation of implicatures. More generally our
findings illustrate how intonation interacts at a cognitive level with pragmatic
inference.
PMID- 28697696
TI - Processing Intonationally Implicated Contrast versus Negation in American
English.
AB - Certain English intonational contours facilitate a conversational implicature
that a relevant alternative to the stated proposition does not hold true. We
evaluated how frequently and how quickly naive participants achieved such
pragmatically enriched meanings when their attention had not already been drawn
to a set of alternatives. Sentences with L+H* L-H% intonational contours, along
with broad focus affirmative and negative counterparts, were tested in a pair of
experiments. Experiment 1 revealed that most interpretations of the L+H* L-H%
sentences evidenced the expected implicature, but a substantial number did not.
Experiment 2 mapped the activation levels across time for the asserted state and
a contradictory/implicated alternative for the same three sentence types, using a
picture-naming paradigm. The results revealed that lexical negation produced a
contrast in activation levels between the two alternatives at an earlier time
point than the L+H* L-H% contour, and that the relative activation of the two
states shifted over time for L+H* L-H% sentences, such that an intonationally
implicated alternative was highly activated at a time point when the activation
for the asserted meaning had declined. These results further our understanding of
the pragmatic processes involved in the interpretation of negation and
intonation.
PMID- 28697697
TI - Postfocal Downstep in German.
AB - This article is a follow-up study of Fery and Kugler (2008. Pitch accent scaling
on given, new and focused constituents in German. Journal of Phonetics, 36, 680
703). It reports on an experiment of the F0 height of potential pitch accents in
the postfocal region of German sentences and addresses in this way an aspect of
the influence of information structure on the intonation of sentences that was
left open in the previous article. The results of the experiment showed that,
when several constituents are located in this position, they are often in a
downstep relation, but are rarely upstepped. In 37% of the cases, the pitch
accents are only realized dynamically and there is no down- or upstepping. We
interpret these results as evidence that postfocal constituents are phrased
independently. The data examined speak against a model of postfocal intonation in
which postfocal phrasing is eliminated and all accents are reduced to zero.
Instead, the pitch accents are often present, although reduced. Moreover, the
facts support the existence of prosodic phrasing of the postfocal constituents;
the postfocal position implies an extremely compressed register, but no
dephrasing or systematic complete deaccentuation of all pitch accents. We propose
adopting a model of German intonation in which prosodic phrasing is determined by
syntactic structure and cannot be changed by information structure. The role of
information structure in prosody is limited to changes in the register
relationship of the different parts of the sentence. Prefocally, there is no or
only little register compression because of givenness. Postfocally, register
compression is the rule. A model of intonation must take this asymmetry into
account.
PMID- 28697698
TI - Intonation and Evidentiality in Spanish Polar Interrogatives.
AB - Three different nuclear pitch accents can be found in Castilian Spanish polar
interrogatives. In addition to the 'canonical' low-rise pattern, there are two
marked interrogative contours featuring high-rise and rise-fall pitch accents.
The aim of this paper is to explain how each contour contributes to the
interpretation of the utterance in which they occur. I argue that this
contribution is to be sought at the semantic, not at the pragmatic-illocutionary,
attitudinal-level. My proposal is that the low-rise contour is the expression of
unspecified sentence polarity (corresponding to the interrogative operator),
whereas the two marked contours add indications about the information source-that
is, they encode evidential distinctions. The high-rise pattern indicates that the
Self is the source of the information; the rise-fall tone indicates that Other is
the source. The whole range of pragmatic interpretations that have been described
in the literature can be easily accommodated into the present proposal as
inferential developments of the encoded meaning together with contextual
information. This view has implications for a theory of interrogatives, for the
phonology of intonation and for the articulation of the semantics/pragmatics
interface.
PMID- 28697699
TI - Effects of Word Frequency and Transitional Probability on Word Reading Durations
of Younger and Older Speakers.
AB - High-frequency units are usually processed faster than low-frequency units in
language comprehension and language production. Frequency effects have been shown
for words as well as word combinations. Word co-occurrence effects can be
operationalized in terms of transitional probability (TP). TPs reflect how
probable a word is, conditioned by its right or left neighbouring word. This
corpus study investigates whether three different age groups-younger children (8
12 years), adolescents (12-18 years) and older (62-95 years) Dutch speakers-show
frequency and TP context effects on spoken word durations in reading aloud, and
whether age groups differ in the size of these effects. Results show consistent
effects of TP on word durations for all age groups. Thus, TP seems to influence
the processing of words in context, beyond the well-established effect of word
frequency, across the entire age range. However, the study also indicates that
age groups differ in the size of TP effects, with older adults having smaller TP
effects than adolescent readers. Our results show that probabilistic reduction
effects in reading aloud may at least partly stem from contextual facilitation
that leads to faster reading times in skilled readers, as well as in young
language learners.
PMID- 28697700
TI - Communicative Success in Spatial Dialogue: The Impact of Functional Features and
Dialogue Strategies.
AB - This paper addresses the impact of dialogue strategies and functional features of
spatial arrangements on communicative success. To examine the sharing of
cognition between two minds in order to achieve a joint goal, we collected a
corpus of 24 extended German-language dialogues in a referential communication
task that involved furnishing a dolls' house. Results show how successful
communication, as evidenced by correct placement of furniture items, is affected
by: (a) functionality of the furniture arrangement; (b) previous task experience;
and (c) dialogue features such as description length and orientation information.
To enhance research in this area, our 'Dolldialogue' corpus (
www.dolldialogue.space ) is now available as a free resource.
PMID- 28697701
TI - Introduction to the Special Section: Intonational constraints on pragmatic
inferences.
PMID- 28697702
TI - Experimental Evidence for the Role of Intonation in Evidential Marking.
AB - This paper investigates the role of intonation in the marking of directly
perceived information in Majorcan Catalan polar questions. We conducted a
perception experiment in which a total of 72 participants were introduced to a
set of twins who were exposed to different types of evidence for a given
p(roposition). One twin inferred p based on direct sensory information (via one
of the five senses), while the other had been told that p by a third party, that
is, reported information. Participants listened to a set of discourse contexts
that ended in critical stimuli with three attested combinations of
particle/intonation in this variety of Catalan: (1) polar questions produced with
a falling nuclear contour !H+L* L%; (2) polar questions headed with the particle
que 'that' produced with !H+L* L%; and (3) polar questions headed with the
particle que and produced with a rise-fall L+H* L%. After hearing the stimulus,
participants had to decide which of the twins had uttered the question-the one
who inferred a proposition ( p) based on direct sensory information or the one
who had been told p by a third party. The results show that listeners very
consistently associate the que + L+H* L% combination with inferences drawn from
direct sensory evidence as opposed to reported evidence. This shows that
particles may work in tandem with intonation to convey the information source.
Importantly, we show that intonation is a part of grammar that may be recruited
for evidential strategies.
PMID- 28697703
TI - Retrospective analysis of the effect of aflibercept loading dose on the retinal
vessel diameters in patients with treatment-naive neovascular AMD.
AB - BACKGROUND: To evaluate the effects of intravitreal aflibercept (IVA) on retinal
vessel diameters in patients with neovascular age-related macular degeneration
(AMD). DESIGN, SETTING, AND PARTICIPANTS: A retrospective study conducted at the
Kutahya Dumlupinar University Faculty of Medicine included 15 eyes of 15 patients
with treatment naive neovascular AMD. METHODS: All eyes received IVA injections
once per month for 3 months; untreated contralateral eyes were used as controls.
The central retinal artery equivalent (CRAE), central retinal vein equivalent
(CRVE), and artery-vein ratio (AVR) values were measured using a computer-based
program before the first IVA injection and 30 days after the first, second, and
third injections. The main outcome measurements were the central macular
thickness (CMT), best-corrected visual acuity (BCVA), choroidal thickness, CRAE,
CRVE, and AVR. RESULTS: Significant vasoconstriction of the retinal arterioles
was observed in all eyes treated with IVA when compared to baseline (p = 0.009).
However, no significant differences were found for CRVE or AVR throughout the
study period in treated eyes. In the control group, all parameters measured
during each visit were similar to baseline measurements (p > 0.05). The mean BCVA
significantly improved at the end of the loading dose of IVA, when compared to
baseline (p = 0.006). After the IVA injections, the mean CMT and choroidal
thickness were significantly reduced at all visits, compared to baseline (p <
0.001). CONCLUSIONS: The current study showed that IVA led to significant retinal
arteriolar vasoconstriction and choroidal thinning, which may cause reduced
retinal blood flow.
PMID- 28697704
TI - Radio Gaga? Intra-team communication of Australian Rules Football umpires -
effect of radio communication on content, structure and frequency.
AB - Intra-team communication plays an important role in team effectiveness in various
domains including sport. As such, it is a key consideration when introducing new
tools within systems that utilise teams. The difference in intra-team
communication of Australian Rules Football (AFL) umpiring teams was studied when
umpiring with or without radio communications technology. A cross-sectional
observational study was conducted to analyse the verbal communication of seven
umpiring teams (20 participants) grouped according to their experience with radio
communication. The results identified that radio communication technology
increased the frequency and altered the structure of intra-team communication.
Examination of the content of the intra-team communication identified impacts on
the 'Big Five' teamwork behaviours and associated coordinating mechanisms.
Analysis revealed that the communications utilised did not align with the closed
loop form of communication described in the Big Five model. Implications for
teamwork models, coaching and training of AFL umpires are discussed. Practitioner
Summary: Assessing the impact of technology on performance is of interest to
ergonomics practitioners. The impact of radio communications on teamwork is
explored in the highly dynamic domain of AFL umpiring. When given radio
technology, intra-team communication increased which supported teamwork
behaviours, such as backup behaviour and mutual performance monitoring.
PMID- 28697705
TI - Sad people are more accurate at expression identification with a smaller own
ethnicity bias than happy people.
AB - Sad individuals are more accurate at face identity recognition, possibly because
they scan more of the face during encoding. During expression identification
tasks, sad individuals do not fixate on the eyes as much as happier individuals.
Fixating on features other than the eyes leads to a reduced own-ethnicity bias.
This background indicates that sad individuals would not view the eyes as much as
happy individuals, and this would result in improved expression recognition and
reduced own-ethnicity bias. This prediction was tested using an expression
identification task with eye tracking. We demonstrate that sad-induced
participants show enhanced expression recognition and a reduced own-ethnicity
bias than happy-induced participants due to scanning more facial features. We
conclude that mood affects eye movements and face encoding by causing a wider
sampling strategy and deeper encoding of facial features diagnostic for
expression identification.
PMID- 28697706
TI - Improving the development, monitoring and reporting of stroke rehabilitation
research: Consensus-based core recommendations from the Stroke Recovery and
Rehabilitation Roundtable.
AB - Recent reviews have demonstrated that the quality of stroke rehabilitation
research has continued to improve over the last four decades but despite this
progress, there are still many barriers in moving the field forward. Rigorous
development, monitoring and complete reporting of interventions in stroke trials
are essential in providing rehabilitation evidence that is robust, meaningful and
implementable. An international partnership of stroke rehabilitation experts
committed to develop consensus-based core recommendations with a remit of
addressing the issues identified as limiting stroke rehabilitation research in
the areas of developing, monitoring and reporting stroke rehabilitation
interventions. Work exploring each of the three areas took place via multiple
teleconferences and a two-day meeting in Philadelphia in May 2016. A total of 15
recommendations were made. To validate the need for the recommendations, the
group reviewed all stroke rehabilitation trials published in 2015 (n = 182
papers). Our review highlighted that the majority of publications did not clearly
describe how interventions were developed or monitored during the trial. In
particular, under-reporting of the theoretical rationale for the intervention and
the components of the intervention call into question many interventions that
have been evaluated for efficacy. More trials were found to have addressed the
reporting of interventions recommendations than those related to development or
monitoring. Nonetheless, the majority of reporting recommendations were still not
adequately described. To progress the field of stroke rehabilitation research and
to ensure stroke patients receive optimal evidence-based clinical care, we urge
the research community to endorse and adopt our recommendations.
PMID- 28697707
TI - Editorial.
PMID- 28697708
TI - Agreed definitions and a shared vision for new standards in stroke recovery
research: The Stroke Recovery and Rehabilitation Roundtable taskforce.
AB - The first Stroke Recovery and Rehabilitation Roundtable established a game
changing set of new standards for stroke recovery research. Common language and
definitions were required to develop an agreed framework spanning the four
working groups: translation of basic science, biomarkers of stroke recovery,
measurement in clinical trials and intervention development and reporting. This
paper outlines the working definitions established by our group and an agreed
vision for accelerating progress in stroke recovery research.
PMID- 28697709
TI - Standardized measurement of sensorimotor recovery in stroke trials: Consensus
based core recommendations from the Stroke Recovery and Rehabilitation
Roundtable.
AB - Finding, testing and demonstrating efficacy of new treatments for stroke recovery
is a multifaceted challenge. We believe that to advance the field,
neurorehabilitation trials need a conceptually rigorous starting framework. An
essential first step is to agree on definitions of sensorimotor recovery and on
measures consistent with these definitions. Such standardization would allow
pooling of participant data across studies and institutions aiding meta-analyses
of completed trials, more detailed exploration of recovery profiles of our
patients and the generation of new hypotheses. Here, we present the results of a
consensus meeting about measurement standards and patient characteristics that we
suggest should be collected in all future stroke recovery trials. Recommendations
are made considering time post stroke and are aligned with the international
classification of functioning and disability. A strong case is made for addition
of kinematic and kinetic movement quantification. Further work is being
undertaken by our group to form consensus on clinical predictors and pre-stroke
clinical data that should be collected, as well as recommendations for additional
outcome measurement tools. To improve stroke recovery trials, we urge the
research community to consider adopting our recommendations in their trial
design.
PMID- 28697710
TI - Enhancing the alignment of the preclinical and clinical stroke recovery research
pipeline: Consensus-based core recommendations from the Stroke Recovery and
Rehabilitation Roundtable translational working group.
AB - Stroke recovery research involves distinct biological and clinical targets
compared to the study of acute stroke. Guidelines are proposed for the pre
clinical modeling of stroke recovery and for the alignment of pre-clinical
studies to clinical trials in stroke recovery.
PMID- 28697711
TI - Biomarkers of stroke recovery: Consensus-based core recommendations from the
Stroke Recovery and Rehabilitation Roundtable.
AB - The most difficult clinical questions in stroke rehabilitation are "What is this
patient's potential for recovery?" and "What is the best rehabilitation strategy
for this person, given her/his clinical profile?" Without answers to these
questions, clinicians struggle to make decisions regarding the content and focus
of therapy, and researchers design studies that inadvertently mix participants
who have a high likelihood of responding with those who do not. Developing and
implementing biomarkers that distinguish patient subgroups will help address
these issues and unravel the factors important to the recovery process. The goal
of the present paper is to provide a consensus statement regarding the current
state of the evidence for stroke recovery biomarkers. Biomarkers of motor,
somatosensory, cognitive and language domains across the recovery timeline post
stroke are considered; with focus on brain structure and function, and exclusion
of blood markers and genetics. We provide evidence for biomarkers that are
considered ready to be included in clinical trials, as well as others that are
promising but not ready and so represent a developmental priority. We conclude
with an example that illustrates the utility of biomarkers in recovery and
rehabilitation research, demonstrating how the inclusion of a biomarker may
enhance future clinical trials. In this way, we propose a way forward for when
and where we can include biomarkers to advance the efficacy of the practice of,
and research into, rehabilitation and recovery after stroke.
PMID- 28697712
TI - Intravenous administration of tirofiban versus loading dose of oral clopidogrel
for preventing thromboembolism in stent-assisted coiling of intracranial
aneurysms.
AB - Background Thromboembolic complications after stenting of intracranial aneurysms
may be affected by antiplatelet administration. Aims This retrospective study
aimed to assess the safety of intravenous tirofiban versus loading dose of oral
clopidogrel for preventing thromboembolism in stent-assisted coiling of
intracranial aneurysms. Methods From January 2006 to December 2013, 281 patients
with cerebral aneurysms were treated with stent-coiling using two antiplatelet
strategies in comparison: the initial strategy (a loading dose of >=300 mg
clopidogrel followed by dual antiplatelet, clopidogrel group) and the modified
strategy (intravenous administration of tirofiban 8 ug/kg over 3 min followed by
a maintenance dose of 0.1 ug/kg/min for 24 h, tirofiban group). The end points
were rates of perioperative thromboembolic events and intracranial hemorrhages.
Results Thromboembolic events were observed more often in the clopidogrel group
(13/120 aneurysms, 10.83%) than the tirofiban group (6/178 aneurysms, 3.37%; P =
0.010), with no increase in the rate of intracranial hemorrhages ( P = 0.164). In
the ruptured subgroups, thromboembolic events were significantly fewer in the
tirofiban subgroup (5/128, 3.91%) compared with the clopidogrel subgroup (7/53,
13.21%; P = 0.043) with no increase in the rate of hemorrhage ( P = 0.360).
Conclusions Intravenous administration of tirofiban is safe in intracranial
aneurysms treated with stent-assisted coiling.
PMID- 28697713
TI - An update of the Italian Stroke Organization-Stroke Prevention Awareness
Diffusion Group guidelines on carotid endarterectomy and stenting: A personalized
medicine approach.
AB - Although proof-based medicine has generated much valid evidence for the drawing
up of guidelines and recommendations for best clinical practice in symptomatic
and asymptomatic carotid stenosis, whether and when it is better to employ
endarterectomy or stenting as the intervention of choice still remain matters of
debate. Moreover, guidelines have been targeted up to now to the 'representative'
patient, as resulting from the statistical analyses of the studies conducted on
the safety and efficacy of both interventions as well as on medical therapy
alone. The Italian Stroke Organization (ISO) and Stroke Prevention and Awareness
Diffusion (SPREAD) group has thus decided to update its statements for an 8th
edition. To this end, a multidisciplinary team of authors representing Italian
scientific societies in the neurology, neuroradiology, vascular and endovascular
surgery, interventional cardiology, and general medicine fields re-examined the
literature available on stroke. Analyses and considerations on patient subgroups
have allowed to model the risks/benefits of endarterectomy and stenting in the
individual. Accordingly, the guideline's original methodology has been revised to
follow the new SIGN (Scottish Intercollegiate Guideline Network) Grade-like
approach, integrating it with new considerations on Precision, or Personalized
Medicine. Therefore, this guideline offers recommendations on precision medicine
for the single patient, and can be followed in addition to the more standard
guidelines.
PMID- 28697714
TI - Association Between Overweight and Renal Transplant Outcomes: A Meta-Analysis.
AB - OBJECTIVES: As the demand for kidney transplant allografts has increased, many
centers are expanding the upper limit of acceptable body mass index for kidney
donors. However, obesity is a risk factor for developing renal disease. Our goal
was to quantify body mass index trends in donor nephrectomy patients and to
institute nutrition counseling to promote sustainable weight loss to reduce the
risk of metabolic syndrome-derived renal dysfunction. MATERIALS AND METHODS:
Ninety patients who underwent donor nephrectomy between 2007 and 2012 consented
to having height and weight data collected at multiple time points. After data
collection, each patient underwent a standardized nutrition counseling session.
One year later, body mass index was reassessed. RESULTS: Preoperatively, 52% of
the patients were overweight or obese. The percentage of overweight and obese
patients remained stable for 2 years after surgery. However, at 3, 4, and 5 years
after surgery, these rates increased to 59%, 69%, and 91%. Each patient was
counseled about obesity-related comorbidities and provided information about
lifestyle modification. One year later, 94% of previously overweight patients and
82% of previously obese patients had a decrease in mean body mass index from 27.2
+/- 4.0 kg/m2 to 25.1 +/- 3.6 kg/m2. CONCLUSIONS: Living-donor nephrectomy
patients are at risk of developing obesity, similar to the adult population.
Nutrition counseling may be beneficial to help normalize body mass index in
patients who have become overweight or obese to potentially prevent obesity
related comorbidities. All patients were evaluated by a nutrition specialist
after surgery to review our donor nephrectomy nutrition brochure. Body mass index
monitoring and primary care follow-up appear to be appropriate surveillance
methods.
PMID- 28697715
TI - Conversion From Once-Daily Prolonged-Release Tacrolimus to Once-Daily Extended
Release Tacrolimus in Stable Liver Transplant Recipients.
AB - OBJECTIVES: After organ transplant, strategies to simplify the therapeutic
regimen may improve adherence and prevent rejection and/or graft loss. The aim of
the present study was to evaluate the safety of conversion from once-daily
prolonged-release tacrolimus (Advagraf; Astellas Pharma Europe Limited,
Middlesex, UK) to once-daily extended-release tacrolimus (Envarsus; Chiesi SAS,
Nanterre, France) in stable adult liver transplant recipients. MATERIALS AND
METHODS: This observational study inclu-ded 44 liver transplant patients (median
age of 59 y; 63.6% men; median delay after transplant of 72.5 mo). Conversion was
based on a 1:0.70 proportion. RESULTS: Mean dose of tacrolimus was 2.65 +/- 1.24
mg/day before conversion and 2.09 +/- 1.68 mg/day after conversion (P < .05),
with ratio of 1:0.79. Mean serum tacrolimus trough level increased after
conversion (4.92 +/- 1.65 vs 5.60 +/- 2.89 ng/mL; P < .05), with ratio of 1:1.14.
Six months after conversion, mean dose of tacrolimus was 1.65 +/- 0.93 mg/day
(ratio of 1:0.62) and mean serum tacrolimus trough level was 4.82 +/- 1.85 ng/mL,
similar to the initial level before conversion. At the end of follow-up, 2
patients had returned to once-daily prolonged-release tacrolimus because of
adverse effects (allergy, digestive trouble), which resolved thereafter. The mean
cost of tacrolimus therapy was 5.54 +/- 2.29 Euros/patient/day before conversion
and 4.11 +/- 2.32 Euros/patient/day after conversion (P < .05). CONCLUSIONS:
Conversion from prolonged-release to extended-release tacrolimus in stable liver
transplant patients is safe and cost-effective; however, initially, dose
adaptations and careful monitoring are required.
PMID- 28697716
TI - Case Series of 10 Patients with Cirrhosis Undergoing Emergent Repair of Ruptured
Umbilical Hernias: Natural History and Predictors of Outcomes.
AB - OBJECTIVES: Ascites represents an important event in the natural history of
cirrhosis, portending increased 1-year mortality. Umbilical herniation with
rupture is an uncommon complication of large-volume ascites that is associated
with significant morbidity and mortality. The aim of this study was to describe
predictors of outcomes in patients undergoing emergent repair for spontaneous
umbilical hernia rupture. MATERIALS AND METHODS: We report a case series of 10
patients with decompensated cirrhosis (mean age 66 +/- 9 years, mean Model for
End-Stage Liver Disease score of 21 +/- 7) who presented with a ruptured
umbilical hernia and had emergent repair. RESULTS: Thirty percent (3/10) of
patients died or required liver transplant. Factors associated with death or
transplant included the development of bacterial peritonitis (P = .03) and the
presurgical 30-day Mayo Clinic Postoperative Mortality Risk in Patient with
Cirrhosis Score (P = .03). CONCLUSIONS: Emergent repair after umbilical hernia
rupture in patients with decompensated cirrhosis carries a poor prognosis with
30% of patients developing poor postsurgical outcomes.
PMID- 28697717
TI - Timing and Predictors of Early Urologic and Infectious Complications After Renal
Transplant: An Analysis of a New York Statewide Database.
AB - OBJECTIVES: The most common complications after renal transplant are urologic and
are a cause of significant morbidity in a vulnerable population. We sought to
characterize the timing and predictors of urologic complications after renal
transplant using a statewide database. MATERIALS AND METHODS: We queried the New
York Statewide Planning and Research Cooperative System database to identify
patients who underwent renal transplant from 2005 to 2013. Postoperative
complications included hydronephrosis, ureteral stricture, vesicoureteral reflux,
nephrolithiasis, and urinary tract infections. Cox proportional hazards model was
used to assess independent predictors of urologic complications. RESULTS: In
total, 9038 patients were included in the analyses. Urologic complications
occurred in 11.3% of patients and included hydronephrosis (12.0%),
nephrolithiasis (2.8%), ureteral stricture (2.4%), and vesicoureteral reflux
(1.5%). We found that 23% experienced at least one urinary tract infection. On
multivariate analysis, predictors of urologic complications included medicare
insurance, hypertension, and prior urinary tract infection. Graft recipients from
living donors were less likely to experience urologic complications than deceased
donor kidney recipients (P < .001). CONCLUSIONS: Urologic complications occur in
a significant proportion of renal transplants. Further study is needed to
identify risk factors for complications after renal transplantation to decrease
morbidity in this vulnerable population.
PMID- 28697718
TI - High Survival and Mortality Characteristics in Heart Transplant Patients at a
National Institute.
AB - OBJECTIVES: The identification of variables related to the survival of heart
transplant patients is vital for a good medical practice. Few studies have
examined this issue in a Latin American population. Therefore, the aim of this
study was to analyze, retrospectively, the survival and mortality characteristics
of patients after heart transplant. MATERIALS AND METHODS: Information on
patients was obtained through review of medical records; we collected information
on all patients who underwent this procedure from 2010 to 2015. Sociodemographic,
clinical, and surgical characteristics associated with posttransplant mortality
were analyzed. Survival over 5 years was determined with the Kaplan-Meier method.
RESULTS: The overall survival rate of the 35 patients who underwent heart
transplant was 85%. Those with low total cholesterol values (< 160 mg/dL) had a
lower survival at 5 years than patients with higher values (74% vs 100%; P =
.044). The overall mortality was 14.3%, and the main cause of death was
acutegraft rejection (40%). Lower total cholesterol level (< 160 mg/dL; P =
.036), presence of chronic kidney disease stage 1 (P = .049), intraoperative
bleeding (> 600 mL; P = .013), and number of sepsis incidents (P = .03) were more
frequent in patients who died. CONCLUSIONS: The survival in our institute at 5
years is higher than shown in the reported literature, and the mortality is
lower. In addition, a low total cholesterol value negatively affects survival of
heart transplant patients at 5 years.
PMID- 28697719
TI - High Position of the Third Renal Transplant and Alternative Urinary Tract
Reconstruction in a Complicated Case.
AB - The decision-making process for treatment of patients with end-stage renal
failure, multiple failed renal transplants, and severe comorbidities can be
exceedingly difficult due to the inapplicability of many common surgery methods.
In this article, we report the treatment of such a patient who underwent a third
renal transplant and subsequently developed a ureteral stenosis. The third kidney
had been transplanted with a high abdominal position and a partially intra- and
retroperitoneally placed ureter due to a bilaterally obtained iliac fossa and
severe abdominal adhesions. For the severe ureteric stenosis, an alternative
urinary tract reconstruction was developed by making use of the native ureter
contralateral to the graft by tunneling under the sigmoid. We recommend this
surgical method as a valid alternative for patients with severe ureteric graft
stenosis, when treatment with stenting and common surgical ureter reconstruction
methods are not feasible.
PMID- 28697720
TI - Early-Onset Pneumonia After Liver Transplant: Microbial Causes, Risk Factors, and
Outcomes, Mansoura University, Egypt, Experience.
AB - OBJECTIVES: Pneumonia has a negative effect on the outcome of liver transplant.
Our aim was to analyze early-onset pneumonia that developed within the first
month after transplant. MATERIALS AND METHODS: This prospective single-center
study included 56 adult living-donor liver transplant recipients; those who
developed early-onset pneumonia based on clinical and radiologic criteria were
investigated as to causative pathogens and then followed up and compared with
other recipients without pneumonia to illustrate risk factors, outcomes, and
related mortality of posttransplant pneumonia. RESULTS: Twelve patients (21.4%)
developed early-onset pneumonia with mortality rate of 75% (9 of 12). Sixteen
pathogens were isolated; extended spectrum beta-lactamase producing
Enterobacteriaceae were the most common (31.2%) followed by carbapenem-producing
Enterobacteriaceae and methicillin-resistant Staphylococcus aureus (18.8%). Fungi
were isolated in 3 cases that were also coinfected with bacteria. Diabetes
mellitus (P = .042), liberal postoperative fluid therapy (P = .028), prolonged
posttransplant intensive care unit stay (P = .01), atelectasis grade >= 2 (P <=
.001), and calcineurin inhibitor-induced neurotoxicity (P = .04) were risk
factors for early posttransplant pneumonia. CONCLUSIONS: Pneumonia is the leading
cause of early mortality after liver transplant. The emergence of multidrug
resistant bacteria is major issue associated with a high rate of treatment
failure.
PMID- 28697721
TI - Editorial: Cures of Vascular Disease - The State.
PMID- 28697722
TI - Introduction of a novel service model to improve uptake and adherence with
cardiac rehabilitation within Buckinghamshire Healthcare NHS Trust.
AB - BACKGROUND: Buckinghamshire Healthcare NHS Trust (BHT) carried out a cardiac
rehabilitation (CR) service redesign aimed at optimising patient recruitment and
retention and decreasing readmissions. METHODS: A single centre observational
study and local service evaluation were carried out to describe the impact of the
novel technology-enabled CR model. Data were collected for adult patients
referred for CR at BHT, retrospectively for patients referred during the 12-month
pre-implementation period (Cohort 1) and prospectively for patients referred
during the 12-month post-implementation period (Cohort 2). The observational
study included 350 patients in each cohort, seasonally matched; the service
evaluation included all eligible patients. No data imputation was performed.
RESULTS: In the observational study, a higher proportion of referred patients
entered CR in Cohort 2 (84.3%) than Cohort 1 (76.0%, P = 0.006). Fewer patients
in Cohort 2 had >=1 cardiac-related emergency readmission within 6 months of
discharge (4.3%) than Cohort 1 (8.9%, P = 0.015); readmissions within 30 days and
12 months were not significantly different. Median time to CR entry from
discharge was significantly shorter in Cohort 2 (35.0 days) than Cohort 1 (46.0
days, P < 0.001). The CR completion rate was significantly higher in Cohort 2
(75.6%) than Cohort 1 (47.4%, P < 0.001); median CR duration for completing
patients was significantly longer in Cohort 2 (80.0 days) than Cohort 1 (49.0
days, P < 0.001). Overall, similar results were observed in the service
evaluation. CONCLUSIONS: Introduction of the novel technology-enabled CR model
was associated with short-term improvements in emergency readmissions and
sustained increases in CR entry, duration and completion.
PMID- 28697723
TI - Implementation fidelity of a self-management course for epilepsy: method and
assessment.
AB - BACKGROUND: Complex interventions such as self-management courses are difficult
to evaluate due to the many interacting components. The way complex interventions
are delivered can influence the effect they have for patients, and can impact the
interpretation of outcomes of clinical trials. Implementation fidelity evaluates
whether complex interventions are delivered according to protocol. Such
assessments have been used for one-to-one psychological interventions; however,
the science is still developing for group interventions. METHODS: We developed
and tested an instrument to measure implementation fidelity of a two-day self
management course for people with epilepsy, SMILE(UK). Using audio recordings, we
looked at adherence and competence of course facilitators. Adherence was assessed
by checklists. Competence was measured by scoring group interaction, an overall
impression score and facilitator "didacticism". To measure "didacticism", we
developed a novel way to calculate facilitator speech using computer software.
Using this new instrument, implementation fidelity of SMILE(UK) was assessed on
three modules of the course, for 28% of all courses delivered. RESULTS: Using the
instrument for adherence, scores from two independent raters showed substantial
agreement with weighted Kappa of 0.67 and high percent agreement of 81.2%. For
didacticism, the results from both raters were highly correlated with an
intraclass coefficient of 0.97 (p < 0.0001). We found that the courses were
delivered with a good level of adherence (> 50% of scored items received the
maximum of 2 points) and high competence. Groups were interactive (mean score:
1.9-2.0 out of 2) and the overall impression was on average assessed as "good".
Didacticism varied from 42% to 93% of total module time and was not associated
with the other competence scores. CONCLUSION: The instrument devised to measure
implementation fidelity was reproducible and easy to use. The courses for the
SMILE(UK) study were delivered with a good level of adherence to protocol while
not compromising facilitator competence. TRIAL REGISTRATION: ISRCTN57937389 .
PMID- 28697724
TI - Early characteristics of infants with pulmonary hypertension in a referral
neonatal intensive care unit.
AB - BACKGROUND: Approximately 8-23% of premature infants develop pulmonary
hypertension (PH), and this diagnosis confers a higher possibility of mortality.
As a result, professional societies recommend PH screening in premature infants.
However, the risk factors for and the outcomes of PH may differ depending on the
timing of its diagnosis, and little evidence is available to determine at-risk
infants in the referral neonatal population. The objective of this study was to
define clinical and echocardiographic characteristics of infants with pulmonary
hypertension during the neonatal hospital course and at or near-term . METHODS:
Infants who had the following billing codes: < 32 weeks, birth weight < 1500 g,
neonatal unit, and echocardiograph had records abstracted from a data warehouse
at Children's Healthcare of Atlanta. The outcome was defined as late PH on the
final echocardiogram for all patients, and, separately, for patients with
multiple studies. Descriptive statistics, univariable, and multivariable models
were evaluated, and odds ratios and 95% confidence intervals are expressed below
as (OR, CI). RESULTS: 556 infants were included in the overall study, 59 had PH
on their final echocardiogram (11%). In multivariable analyses, atrial septal
defect (2.9, 1.4-6.1), and intrauterine growth restriction (2.7, 1.2-6.3)
increased the odds of late PH, whereas caffeine therapy decreased PH (0.4, 0.2
0.8). When the analyses were restricted to 32 infants who had multiple
echocardiograms during their hospitalization, the association between atrial
septal defect (5.9, 2.0-16.5) and growth restriction (3.7, 1.3-10.7) and late PH
was strengthened, but the effect of caffeine therapy was no longer significant.
In this smaller subgroup, infants with late PH had their final echocardiogram at
a median of 116 days of life, and 42-74% of them had right ventricular pathology.
CONCLUSIONS: Early clinical variables are associated with PH persistence in a
referral neonatal population. Identification of early clinical factors may help
guide the ascertainment of infant risk for late PH, and may aid in targeting sub
groups that are most likely to benefit from PH screening.
PMID- 28697725
TI - The role of family and school-level factors in bullying and cyberbullying: a
cross-sectional study.
AB - BACKGROUND: Bullying and cyberbullying are common phenomena in schools. These
negative behaviours can have a significant impact on the health and particularly
mental health of those involved in such behaviours, both as victims and as
bullies. This UK study aims to investigate student-level and school-level
characteristics of those who become involved in bullying and cyberbullying
behaviours as victims or perpetrators. METHODS: We used data from 6667 Year 7
students from the baseline survey of a cluster randomized trial in 40 English
schools to investigate the associations between individual-level and school-level
variables with bullying victimization, cyberbullying perpetration, and
cyberbullying victimization. We ran multilevel models to examine associations of
bullying outcomes with individual-level variables and school-level variables.
RESULTS: In multilevel models, at the school level, school type and school
quality measures were associated with bullying risk: students in voluntary-aided
schools were less likely to report bullying victimization (0.6 (0.4, 0.9) p =
0.008), and those in community (3.9 (1.5, 10.5) p = 0.007) and foundation (4.0
(1.6, 9.9) p = 0.003) schools were more likely to report being perpetrators of
cyberbullying than students in mainstream academies. A school quality rating of
"Good" was associated with greater reported bullying victimization (1.3 (1.02,
1.5) p = 0.03) compared to ratings of "Outstanding." CONCLUSIONS: Bullying
victimization and cyberbullying prevalence vary across school type and school
quality, supporting the hypothesis that organisational/management factors within
the school may have an impact on students' behaviour. These findings will inform
future longitudinal research investigating which school factors and processes
promote or prevent bullying and cyberbullying behaviours. TRIAL REGISTRATION:
Trial ID: ISRCTN10751359 Registered: 11/03/2014 (retrospectively registered).
PMID- 28697726
TI - Successful percutaneous coronary intervention in the setting of an aberrant left
coronary artery arising from the right coronary cusp in a patient with acute
coronary syndrome: a case report.
AB - BACKGROUND: An aberrant origin of the left coronary artery (LCA) from the right
coronary cusp (RCC) is an extremely rare congenital anomaly. We here report on
successful percutaneous coronary intervention (PCI) in a patient presenting with
acute coronary syndrome and an aberrant origin of the LCA from the RCC. CASE
PRESENTATION: A 50-year-old man presented at our emergency department with
recurrent resting chest pain. Following unsuccessful attempts at visualizing the
left coronary artery using Judkins left and Amplatz catheters, an aortogram using
a pigtail catheter suggested anomalous left coronary artery origin and showed a
significant occlusive lesion at proximal left anterior descending artery. A
Judkins right 4 guiding catheter was placed around the left coronary ostium and
exchanged for a Judkins left 3.5 guiding catheter after introducing a .014"
coronary long wire into the left circumflex artery. With excellent angiographic
visualization and guide support, a drug-eluting stent was then successfully
implanted. Cardiac computed tomography (CT) demonstrated left coronary artery
origin from right coronary cusp. CONCLUSION: This report presents a case of LCA
originating from the RCC accompanied with acute coronary syndrome that was
treated with successful PCI.
PMID- 28697727
TI - Intermedin attenuates renal fibrosis by induction of heme oxygenase-1 in rats
with unilateral ureteral obstruction.
AB - BACKGROUND: Intermedin [IMD, adrenomedullin-2 (ADM-2)] attenuates renal fibrosis
by inhibition of oxidative stress. However, the precise mechanisms remain
unknown. Heme oxygenase-1 (HO-1), an antioxidant agent, is associated with
antifibrogenic effects. ADM is known to induce HO-1. Whether IMD has any effect
on HO-1 is unclear. Herein, we determined whether the antifibrotic properties of
IMD are mediated by induction of HO-1. METHODS: Renal fibrosis was induced by
unilateral ureteral obstruction (UUO) performed on male Wistar rats. Rat proximal
tubular epithelial cell line (NRK-52E) was exposed to rhTGF-beta1 (10 ng/ml) to
establish an in vitro model of epithelial-mesenchymal transition (EMT). IMD was
over-expressed in vivo and in vitro using the vector pcDNA3.1-IMD. Zinc
protoporphyrin (ZnPP) was used to block HO-1 enzymatic activity. IMD effects on
HO-1 expression in the obstructed kidney of UUO rat and in TGF-beta1-stimulated
NRK-52E were analyzed by real-time RT-PCR, Western blotting or
immunohistochemistry. HO activity in the obstructed kidney, contralateral kidney
of UUO rat and NRK-52E was examined by measuring bilirubin production. Renal
fibrosis was determined by Masson trichrome staining and collagen I expression.
Macrophage infiltration and IL-6 expression were evaluated using
immunohistochemical analysis. In vivo and in vitro EMT was assessed by measuring
alpha-smooth muscle actin (alpha-SMA) and E-cadherin expression using Western
blotting or immunofluorescence, respectively. RESULTS: HO-1 expression and HO
activity were increased in IMD-treated UUO kidneys or NRK-52E. The obstructed
kidneys of UUO rats demonstrated significant interstitial fibrosis on day 7 after
operation. In contrast, kidneys that were treated with IMD gene transfer
exhibited minimal interstitial fibrosis. The obstructed kidneys of UUO rats also
had greater macrophage infiltration and IL-6 expression. IMD restrained
infiltration of macrophages and expression of IL-6 in UUO kidneys. The degree of
EMT was extensive in obstructed kidneys of UUO rats as indicated by decreased
expression of E-cadherin and increased expression of alpha-SMA. In vitro studies
using NRK-52E confirmed these observations. EMT was suppressed by IMD gene
delivery. However, all of the above beneficial effects of IMD were eliminated by
ZnPP, an inhibitor of HO enzyme activity. CONCLUSION: This study demonstrates
that IMD attenuates renal fibrosis by induction of HO-1.
PMID- 28697728
TI - Lower mortality is observed among low birth weight young infants who have
received home-based care by female community health volunteers in rural Nepal.
AB - BACKGROUND: There has been little success in attempts to reduce the proportion of
births with low birth weight (LBW). However, deaths associated with LBW may be
prevented with extra attention to warmth, feeding, and prevention or early
treatment of infections. There are few studies on this in Nepal and in many other
developing countries. This is a cohort study to evaluate the risk of deaths among
LBW infants who received FCHV follow up visit for home-based care compared to
those who did not receive in Rural Nepal. METHODS: A cohort study design was used
with data from the Morang Innovative Neonatal Intervention (MINI) program in
Nepal. Relative Risk (RR) is calculated to compare LBW neonates who received FCHV
follow up visit as compared to LBW neonates who did not receive visit. RESULTS:
Out of 51,853 newborn infants recorded in the MINI database, 2229 LBW neonates
were included in the analysis. The proportion of deaths among those who received
FCHV follow up visit and those who did not receive were 2% (95% CI: 1%; 2%) and
11% (95% CI: 6%; 18%) respectively(P < 0.001). The relative risk of death in LBW
infants who received FCHV follow up visit was 84% less as compared to LBW infants
who did not receive (RR = 0.16; 95% CI: 0.09, 0.29). CONCLUSION: The current
study indicates that to save the lives of LBW young infants simple home-based
measures implemented through trained health volunteers within the existing
government health system may be effective when technically more sophisticated
measures such as tertiary health centers, pediatricians, and expensive technology
are limited.
PMID- 28697729
TI - The relevance of different trust models for representation in patient
organizations: conceptual considerations.
AB - BACKGROUND: Trust within organizations is important for ensuring members'
acceptance of the organization's activities and to expand their scope of action.
Remarkably, Patient Organizations (POs) that often both function as a forum for
self-help and represent patients on the health-political level, have been
understudied in this respect. This paper analyzes the relation between trust and
representation in POs. We distinguish between two models of representation
originating from political theory: the trustee and delegate model and between two
types of trust: horizontal and vertical trust. METHODS: Our theoretical approach
is illustrated with an analysis of 13 interviews with representatives of German
POs. RESULTS: We have found that the delegate model requires horizontal trust and
the trustee model vertical trust. Both models: horizontal/delegate and
vertical/trustee exist within single POs. CONCLUSIONS: The representation process
within POs demands a balancing act between inclusion of affected persons and
strategically aggregating a clear-cut political claim. Trust plays in that
process of coming from individual wishes to collective and political standpoints
a major role both in terms of horizontal as well as vertical trust. Horizontal
trust serves the communication between affected members, and vertical trust
allows representatives to be decisive.
PMID- 28697730
TI - Dietary supplementation of alpha-linolenic acid induced conversion of n-3 LCPUFAs
and reduced prostate cancer growth in a mouse model.
AB - BACKGROUND: alpha-linolenic acid (ALA) is an n-3 polyunsaturated fatty acid
(PUFA) and the substrate for long-chain n-3 PUFAs. The beneficial effects of ALA
on chronic diseases are still in dispute, unlike those of eicosapentaenoic acid
(EPA) and docosahexaenoic acid (DHA). METHODS: The primary objective of this
investigation was to evaluate the efficiency of ALA uptake from a vegetable oil
source and its subsequent conversion to n-3 long-chain PUFAs (LCPUFAs) in the
tissues of growing mice, and to investigate its protective role in a prostate
cancer animal model. We carried out the investigation in prostate-specific Pten
knockout mice with specified low-ALA (L-ALA, 2.5%) and high-ALA (H-ALA, 7.5%)
diets. Total fatty acids in blood, liver, epididymal fat pad, prostate were
detected and prostate weight were adjusted for body weight (mg/25 g). RESULTS: We
found that dietary ALA triggered significant increases in ALA, EPA,
docosapentaenoic acid (DPA) and DHA levels and a significant decrease in
arachidonic acid levels during the mice's growth stage. A dose-dependent effect
was observed for ALA, EPA and DPA, but not DHA. Furthermore, the average prostate
weights in the L-ALA and H-ALA groups were lower than those in the control and n
6 groups, and similar to those in the EPA and n-3 groups. CONCLUSIONS: Our data
suggest that dietary supplementation with ALA is an efficient means of improving
n-3 LCPUFAs in vivo, and it has a biologically effective role to play in prostate
cancer, similar to that of fish oils.
PMID- 28697731
TI - Texture analysis of pulmonary parenchymateous changes related to pulmonary
thromboembolism in dogs - a novel approach using quantitative methods.
AB - BACKGROUND: Diagnosis of pulmonary thromboembolism (PTE) in dogs relies on
computed tomography pulmonary angiography (CTPA), but detailed interpretation of
CTPA images is demanding for the radiologist and only large vessels may be
evaluated. New approaches for better detection of smaller thrombi include dual
energy computed tomography (DECT) as well as computer assisted diagnosis (CAD)
techniques. The purpose of this study was to investigate the performance of
quantitative texture analysis for detecting dogs with PTE using grey-level co
occurrence matrices (GLCM) and multivariate statistical classification analyses.
CT images from healthy (n = 6) and diseased (n = 29) dogs with and without PTE
confirmed on CTPA were segmented so that only tissue with CT numbers between
1024 and -250 Houndsfield Units (HU) was preserved. GLCM analysis and subsequent
multivariate classification analyses were performed on texture parameters
extracted from these images. RESULTS: Leave-one-dog-out cross validation and
receiver operator characteristic (ROC) showed that the models generated from the
texture analysis were able to predict healthy dogs with optimal levels of
performance. Partial Least Square Discriminant Analysis (PLS-DA) obtained a
sensitivity of 94% and a specificity of 96%, while Support Vector Machines (SVM)
yielded a sensitivity of 99% and a specificity of 100%. The models, however,
performed worse in classifying the type of disease in the diseased dog group: In
diseased dogs with PTE sensitivities were 30% (PLS-DA) and 38% (SVM), and
specificities were 80% (PLS-DA) and 89% (SVM). In diseased dogs without PTE the
sensitivities of the models were 59% (PLS-DA) and 79% (SVM) and specificities
were 79% (PLS-DA) and 82% (SVM). CONCLUSION: The results indicate that texture
analysis of CTPA images using GLCM is an effective tool for distinguishing
healthy from abnormal lung. Furthermore the texture of pulmonary parenchyma in
dogs with PTE is altered, when compared to the texture of pulmonary parenchyma of
healthy dogs. The models' poorer performance in classifying dogs within the
diseased group, may be related to the low number of dogs compared to texture
variables, a lack of balanced number of dogs within each group or a real lack of
difference in the texture features among the diseased dogs.
PMID- 28697732
TI - An assessment of equity in the distribution of non-financial health care inputs
across public primary health care facilities in Tanzania.
AB - BACKGROUND: There is limited evidence on how health care inputs are distributed
from the sub-national level down to health facilities and their potential
influence on promoting health equity. To address this gap, this paper assesses
equity in the distribution of health care inputs across public primary health
facilities at the district level in Tanzania. METHODS: This is a quantitative
assessment of equity in the distribution of health care inputs (staff, drugs,
medical supplies and equipment) from district to facility level. The study was
carried out in three districts (Kinondoni, Singida Rural and Manyoni district) in
Tanzania. These districts were selected because they were implementing primary
care reforms. We administered 729 exit surveys with patients seeking out-patient
care; and health facility surveys at 69 facilities in early 2014. A total of
seventeen indices of input availability were constructed with the collected data.
The distribution of inputs was considered in relation to (i) the wealth of
patients accessing the facilities, which was taken as a proxy for the wealth of
the population in the catchment area; and (ii) facility distance from the
district headquarters. We assessed equity in the distribution of inputs through
the use of equity ratios, concentration indices and curves. RESULTS: We found a
significant pro-rich distribution of clinical staff and nurses per 1000
population. Facilities with the poorest patients (most remote facilities) have
fewer staff per 1000 population than those with the least poor patients (least
remote facilities): 0.6 staff per 1000 among the poorest, compared to 0.9 among
the least poor; 0.7 staff per 1000 among the most remote facilities compared to
0.9 among the least remote. The negative concentration index for support staff
suggests a pro-poor distribution of this cadre but the 45 degree dominated the
concentration curve. The distribution of vaccines, antibiotics, anti-diarrhoeal,
anti-malarials and medical supplies was approximately proportional (non
dominance), whereas the distribution of oxytocics, anti-retroviral therapy (ART)
and anti-hypertensive drugs was pro-rich, with the 45 degree line dominating the
concentration curve for ART. CONCLUSION: This study has shown there are
inequities in the distribution of health care inputs across public primary care
facilities. This highlights the need to ensure a better coordinated and equitable
distribution of inputs through regular monitoring of the availability of health
care inputs and strengthening of reporting systems.
PMID- 28697733
TI - Measurement invariance of the strength of motivation for medical school: a multi
group confirmatory factor analysis.
AB - BACKGROUND: The Strength of Motivation for Medical School-Revised (SMMS-R)
questionnaire measures students' motivation for studying medicine. It includes
three subscales: 'willingness to sacrifice', 'readiness to start', and
'persistence'. Measurement invariance is a prerequisite for group comparisons.
The objectives of this study were to verify the factorial structure of the SMMS-R
questionnaire and to investigate it's measurement invariance. METHODS: A total of
989 medical students were approached, 930 cases were kept for data analysis.
Factorial structure of and measurement invariance of the SMMS-R were tested using
single and multiple group confirmatory factor analyses with Mplus. Trational
Cronbach's alpha along with McDonald's omega and glb were used to measure
internal consistency for each subscale. RESULTS: Internal consistency for
subscales and the full instrument were within the acceptable range. A 3-factor
structure of the Chinese version of the SMMS-R was supported. Full configural,
metric and partial scalar invariance were obtained. CONCLUSIONS: The SMMS-R
showed measurement invariance across gender and two independent samples. So it
can be used for group and cross-cultural comparisons.
PMID- 28697734
TI - Factors associated with medication amounts considered excessive among university
students: a questionnaire survey of pharmacy students and those in non-medical
schools.
AB - BACKGROUND: Better insight and knowledge on factors associated with perception of
medication numbers and amounts would contribute greatly to our current
understanding of patient psychological response regarding taking medications, and
would allow us to improve drug administration support and adherence. This study
explored associations between attitudes toward medication dosage in a
questionnaire survey that examined demographic characteristics, the number of
tablets and types of prescription medications considered excessive by
participants, current medication and supplement use, personal experiences with
medications, and perceptions surrounding medications. METHODS: An original
anonymous questionnaire was used for this survey. A total of 934 university
students completed and returned surveys with no missing data. RESULTS: Mean
values +/- standard deviation for excessive thresholds for tablets and types of
medications reported by all participants were 4.21 +/- 1.63 tablets and 4.00 +/-
1.25 medications, respectively. The number of tablets considered excessive was
analyzed using a multiple regression model, which accounted for the variance
(model-adjusted R 2 = 0.095, p < 0.001) between statistically significant
factors, including personal experience with a major illness, supplement use,
aversion to taking medications, gender, university departmental affiliation, and
experience with family members or acquaintances who took excessive amounts of
medications (|beta| > 0.094, p < 0.01). The number of medications considered
excessive was subject to a multiple regression analysis (model-adjusted R 2 =
0.087 p < 0.01), which revealed statistically significant factors, including
personal experience with a major illness, prescription medication use, aversion
to taking medications, gender, university departmental affiliation, and
experience with family members or acquaintances who took excessive amounts of
medications (|beta| > 0.084, p < 0.01). CONCLUSIONS: Individual attitudes toward
medication dosage are influenced by individual factors. Thus, patients should be
provided with personalized advice when they receive medication instructions.
PMID- 28697735
TI - V-J combinations of T-cell receptor predict responses to erythropoietin in end
stage renal disease patients.
AB - BACKGROUND: Anemia is common among end-stage renal disease (ESRD) patients who
undergone hemodialysis. The total reduction of red blood cell (RBC) count is
associated with poor prognosis in these patients. Although erythropoietin (EPO)
has been used as an effective treatment for ESRD patients with anemia, a large
number of patients still present poor responses to EPO treatment. METHODS: We
measured T-cell receptor sequencing profiles, including length of complementarity
deteremining region 3 (CDR3), intra- and inter-group (EPO resistant vs.
responsive) clonotype diversity, V(D)J usage profiles and V-J combinations from
ESRD patients and to investigate the correlation between these features and EPO
treatment efficacy. RESULTS: Our results revealed statistical significance in the
top 3 ~ 15 most abundant joint distributions of Vbeta/Jbeta among the two groups,
suggesting the importance of V or J gene utilization in the EPO response of ESRD
patients. CONCLUSIONS: In summary, we provided evidence addressing the potential
correlation between the immune repertoire and EPO response in ESRD patients.
TRIAL REGISTRATION: TMU-JIRB 201309026. Registered 16 October 2013.
PMID- 28697736
TI - End-of-life perceptions among physicians in intensive care units managed by
anesthesiologists in Germany: a survey about structure, current implementation
and deficits.
AB - BACKGROUND: Structural aspects and current practice about end-of-life (EOL)
decisions in German intensive care units (ICUs) managed by anesthesiologists are
unknown. A survey among intensive care anesthesiologists has been conducted to
explore current practice, barriers and opinions on EOL decisions in ICU. METHODS:
In November 2015, all members of the German Society of Anesthesiology and
Intensive Care Medicine (DGAI) and the Association of German Anesthesiologists
(BDA) were asked to participate in an online survey to rate the presence or
absence and the importance of 50 items. Answers were grouped into three
categories considering implementation and relevance: Category 1 reflects high
implementation and high relevance, Category 2 low and low, and Category 3 low and
high. RESULTS: Five-hundred and forty-one anesthesiologists responded. Only four
items reached >=90% agreement as being performed "yes, always" or "mostly", and
29 items were rated "very" or "more important". A profound discrepancy between
current practice and attributed importance was revealed. Twenty-eight items
attributed to Category 1, six to Category 2 and sixteen to Category 3. Items
characterizing the most urgent need for improvement (Category 3) referred to
patient outcome data, preparation of health care directives and interdisciplinary
discussion, standard operating procedures, implementation of practical
instructions and inclusion of nursing staff and families in the process.
CONCLUSION: The present survey affirms an urgent need for improvement in EOL
practice in German ICUs focusing on advanced care planning, distinct aspects of
changing goals of care, implementation of standard operating procedures,
continuing education and reporting of outcome data.
PMID- 28697737
TI - Radiologic evaluation of orbital index among Ghanaians using CT scan.
AB - BACKGROUND: Orbital index (OI) expresses the proportion of the orbital height to
the orbital width and varies with race, regions within the same race and periods
in evolution. This index is useful in forensic medicine, anthropology and
surgery. However, the average OI among Ghanaian adults was unknown. AIM: The aim
of this study was to determine the orbital index of adult Ghanaians and classify
them under one of the three predetermined groups. METHOD: The study design was a
retrospective cross-sectional. A systematic random sampling method was used for
selecting 350 adult Ghanaian head computed tomography images available from 1
January to 31 December 2015 at KBTH Hospital. The orbital height and orbital
width of each orbit were measured on a 3D CT skull. Data was analysed using
Microsoft Excel and Statistical Package for Social Sciences version 20. RESULTS:
The study had more females than men (167, 47.71%, vs 183, 52.29%). The observed
orbital index of Ghanaians in the study was 81.22 +/- 4.22. The mean orbital
index was 80.52 +/- 4.66 in males and 82.15 +/- 3.83 in females with their
difference being statistically significant (p value <0.05). This placed both
genders in the Microseme category of orbit. There was no significant difference
between the orbital index of the two orbital sides (left and right orbits).
CONCLUSION: The study found Ghanaians in the category of the Microseme and also
indicated a strong sexual dimorphism. The outcome of this study may be useful in
forensic medicine for skull classification and also for better surgical approach
in neurosurgery as well as cosmetic surgery.
PMID- 28697738
TI - An evaluation of the knowledge and perceptions of pharmacy students on
pharmacovigilance activities in Nigeria.
AB - BACKGROUND: The use of the modified-prescription event monitoring technique has
facilitated the understanding and reporting of pharmacovigilance (PV). However,
in Nigeria, PV activities are largely misunderstood. Furthermore, there is a
dearth of information on the knowledge and perceptions of pharmacy students on PV
activities in relation to demographics. This study investigated and assessed the
knowledge and perceptions of pharmacy students about pharmacovigilance as well as
the demographic factors that are related to pharmacovigilance activities.
METHODS: A cross-sectional survey was conducted among final year pharmacy
students in three universities in months of January and February, 2016 with
permission from the institutions and with written consents from 342 respondents.
Pre-tested questionnaire was used to elicit information on the study objectives.
Data were analysed using appropriate descriptive and inferential statistical
techniques. RESULTS: The study revealed that the mean score on knowledge of
pharmacy students on pharmacovigilance activities was 4.3 +/- 0.18 which was
significant according to gender (P < 0.001), students' university (P < 0.001),
and previous exposure to PV subjects (P < 0.001). Sixty-four percent of the
students had positive perceptions about PV activities which was significant at P
< 0.00 according to gender and their various universities. Less than half of the
respondents 165 (48.2%) were able to correctly name the organisation that
collates and document ADR reports in Nigeria. Only 21 (6.1%) of the respondents
gave the correct answer to whether or not all possible ADRs of a drug can be
determined during clinical trials or during pre-marketing phase of drug
assessment. About 204 (59.7%) of the respondents erroneously believed that
adverse reactions caused by cosmetics should not be reported. CONCLUSIONS:
Respondents have inadequate knowledge of PV activities. Therefore, pharmacy
student educators should enhance students' knowledge about PV through training,
during clerkship, and lay more emphasis on relevant PV courses in the Pharmacy
Curriculum.
PMID- 28697739
TI - Effects of transcutaneous electrical nerve stimulation (TENS) on proinflammatory
cytokines: protocol for systematic review.
AB - BACKGROUND: Pain reduction can be achieved by lowering proinflammatory cytokine
levels in the blood. Transcutaneous electrical nerve stimulation (TENS) is a non
invasive physiotherapeutic resource for pain management, but evidence on the
effectiveness of this device at reducing proinflammatory cytokines in the blood
is unclear. This study systematically reviews the literature on the effect of
TENS on proinflammatory cytokines. METHODS: A systematic review protocol was
developed based on searches of articles in six electronic databases and
references of retrieved articles, contact with authors, and repositories of
clinical trials. Eligibility criteria: publication in peer-reviewed journals,
randomized clinical trials, use of TENS in the experimental group, and pre- and
post-measurements of proinflammatory cytokines in the blood. Selection of the
studies and extraction of the data will be carried out by two reviewers
independently. Characteristics of the study, participants, interventions and
outcomes were extracted and described. Assessments were performed on the risk of
bias, level of evidence and the size of the intervention effect in the studies,
according to GRADE guidelines and the Cochrane Handbook for Systematic Reviews.
Clinical and statistical assessments compared the effects of the interventions
(meta-analysis), taking into consideration any influencing characteristics of the
studies (e.g., methods and application sites). DISCUSSION: We anticipate that
this review will strengthen evidence-based knowledge of the effect of TENS on
proinflammatory cytokines and, as a result, direct new studies to benefit
patients with specific pathologies. SYSTEMATIC REVIEW REGISTRATION: PROSPERO,
CRD42017060379 .
PMID- 28697740
TI - Incorporating biological information in sparse principal component analysis with
application to genomic data.
AB - BACKGROUND: Sparse principal component analysis (PCA) is a popular tool for
dimensionality reduction, pattern recognition, and visualization of high
dimensional data. It has been recognized that complex biological mechanisms occur
through concerted relationships of multiple genes working in networks that are
often represented by graphs. Recent work has shown that incorporating such
biological information improves feature selection and prediction performance in
regression analysis, but there has been limited work on extending this approach
to PCA. In this article, we propose two new sparse PCA methods called Fused and
Grouped sparse PCA that enable incorporation of prior biological information in
variable selection. RESULTS: Our simulation studies suggest that, compared to
existing sparse PCA methods, the proposed methods achieve higher sensitivity and
specificity when the graph structure is correctly specified, and are fairly
robust to misspecified graph structures. Application to a glioblastoma gene
expression dataset identified pathways that are suggested in the literature to be
related with glioblastoma. CONCLUSIONS: The proposed sparse PCA methods Fused and
Grouped sparse PCA can effectively incorporate prior biological information in
variable selection, leading to improved feature selection and more interpretable
principal component loadings and potentially providing insights on molecular
underpinnings of complex diseases.
PMID- 28697741
TI - The association between HIV (treatment), pregnancy serum lipid concentrations and
pregnancy outcomes: a systematic review.
AB - BACKGROUND: Observed adverse effects of antiretroviral therapy (ART) on the lipid
profile could be of significance in pregnancy. This systematic review aims to
summarize studies that investigated the association between HIV, ART and serum
lipids during pregnancy and adverse pregnancy outcomes. METHODS: A systematic
search was conducted in five electronic databases to obtain articles that
measured serum lipid concentrations or the incidence of dyslipidaemia in HIV
infected pregnant women. Included articles were assessed for quality according to
the Cochrane Risk of Bias Tool. The extracted data was analysed through
descriptive analysis. RESULTS: Of the 1264 articles screened, 17 articles were
included in this review; eleven reported the incidence of dyslipidaemia, and
twelve on maternal serum lipid concentrations under the influence of HIV
infection and ART. No articles reported pregnancy outcomes in relation to serum
lipids. Articles were of acceptable quality, but heterogenic in methods and study
design. Lipid levels in HIV-infected women increased 1.5-3 fold over the
trimesters of pregnancy, and remained within the physiological reference range.
The percentage of women with dyslipidaemia was variable between the studies [0
88.9%] and highest in the groups on first generation protease inhibitors and for
women on ART at conception. CONCLUSION: This systematic review observed
physiologic concentrations of serum lipids for HIV-infected women receiving ART
during pregnancy. Serum lipids were increased in users of first generation
protease inhibitors and for those on treatment at conception. There was no
information available about pregnancy outcomes. Future studies are needed which
include HIV-uninfected control groups, control for potential confounders, and
overcome limitations associated with included studies.
PMID- 28697742
TI - Increased C4 and decreased C3 levels are associated with a poor prognosis in
patients with immunoglobulin A nephropathy: a retrospective study.
AB - BACKGROUND: An association between serum complement levels and poor renal
prognosis in patients with immunoglobulin A nephropathy (IgAN) remains
controversial. METHODS: We conducted a retrospective study examining the
relationship between serum complement levels and prognosis in patients with IgAN.
Between 2009 and 2013, patients with biopsy-confirmed IgAN were identified from
the Second Affiliated Hospital of Wenzhou Medical College, China, and various
parameters were documented during follow-up until 2015. The definition of the
primary endpoint was a decrease of estimated glomerular filtration rate (eGFR)
more than 30% from their baseline levels. RESULTS: A total of 403 patients (55.3%
female, average 33.7 months of follow-up) were identified and enrolled, with the
primary endpoint occurring in 39 (9.8%) patients. Among the patients selected,
202 (50.1%) received corticosteroid treatment alone or in combination with
another immunosuppressant (GS group), while others did not receive
immunosuppressive treatment (non-GS group). The incidence of the primary endpoint
was slightly lower in the GS group compared to the non-GS group (7.0% versus
12.6%, p = 0.06). Multivariate Cox proportional-hazard regression analyses,
adjusting for age, systolic and diastolic blood pressure, 24-h urine protein, and
immunosuppressive therapy, showed that serum complement 4 (C4) levels (hazard
ratio [HR] 2.4, 95% confidence interval [CI] 1.6-3.8, p < 0.001) and serum
complement 3 (C3) levels (HR 0.6, 95% CI 0.2-0.6, p < 0.001) were significantly
associated with a poor prognosis among patients with IgAN. CONCLUSIONS: We
demonstrated that an increase in serum C4, as well as a decrease in C3, was an
important outcome determinant for patients with IgAN. Testing serum C3 and C4
levels might assist in predicting renal outcomes among these patients.
PMID- 28697743
TI - Integrative analysis of copy number and gene expression in breast cancer using
formalin-fixed paraffin-embedded core biopsy tissue: a feasibility study.
AB - BACKGROUND: An absence of reliable molecular markers has hampered individualised
breast cancer treatments, and a major limitation for translational research is
the lack of fresh tissue. There are, however, abundant banks of formalin-fixed
paraffin-embedded (FFPE) tissue. This study evaluated two platforms available for
the analysis of DNA copy number and gene expression using FFPE samples. METHODS:
The cDNA-mediated annealing, selection, extension, and ligation assay (DASLTM)
has been developed for gene expression analysis and the Molecular Inversion
Probes assay (OncoscanTM), were used for copy number analysis using FFPE tissues.
Gene expression and copy number were evaluated in core-biopsy samples from
patients with breast cancer undergoing neoadjuvant chemotherapy (NAC). RESULTS:
Forty-three core-biopsies were evaluated and characteristic copy number changes
in breast cancers, gains in 1q, 8q, 11q, 17q and 20q and losses in 6q, 8p, 13q
and 16q, were confirmed. Regions that frequently exhibited gains in tumours
showing a pathological complete response (pCR) to NAC were 1q (55%), 8q (40%) and
17q (40%), whereas 11q11 (37%) gain was the most frequent change in non-pCR
tumours. Gains associated with poor survival were 11q13 (62%), 8q24 (54%) and 20q
(47%). Gene expression assessed by DASL correlated with immunohistochemistry
(IHC) analysis for oestrogen receptor (ER) [area under the curve (AUC) = 0.95],
progesterone receptor (PR)(AUC = 0.90) and human epidermal growth factor type-2
receptor (HER-2) (AUC = 0.96). Differential expression analysis between ER+ and
ER- cancers identified over-expression of TTF1, LAF-4 and C-MYB (p <= 0.05), and
between pCR vs non-pCRs, over-expression of CXCL9, AREG, B-MYB and under
expression of ABCG2. CONCLUSION: This study was an integrative analysis of copy
number and gene expression using FFPE core biopsies and showed that molecular
marker data from FFPE tissues were consistent with those in previous studies
using fresh-frozen samples. FFPE tissue can provide reliable information and will
be a useful tool in molecular marker studies. TRIAL REGISTRATION: Trial
registration number ISRCTN09184069 and registered retrospectively on 02/06/2010.
PMID- 28697744
TI - E-learning in graduate medical education: survey of residency program directors.
AB - BACKGROUND: E-learning-the use of Internet technologies to enhance knowledge and
performance-has become a widely accepted instructional approach. Little is known
about the current use of e-learning in postgraduate medical education. To
determine utilization of e-learning by United States internal medicine residency
programs, program director (PD) perceptions of e-learning, and associations
between e-learning use and residency program characteristics. METHODS: We
conducted a national survey in collaboration with the Association of Program
Directors in Internal Medicine of all United States internal medicine residency
programs. RESULTS: Of the 368 PDs, 214 (58.2%) completed the e-learning survey.
Use of synchronous e-learning at least sometimes, somewhat often, or very often
was reported by 85 (39.7%); 153 programs (71.5%) use asynchronous e-learning at
least sometimes, somewhat often, or very often. Most programs (168; 79%) do not
have a budget to integrate e-learning. Mean (SD) scores for the PD perceptions of
e-learning ranged from 3.01 (0.94) to 3.86 (0.72) on a 5-point scale. The odds of
synchronous e-learning use were higher in programs with a budget for its
implementation (odds ratio, 3.0 [95% CI, 1.04-8.7]; P = .04). CONCLUSIONS:
Residency programs could be better resourced to integrate e-learning
technologies. Asynchronous e-learning was used more than synchronous, which may
be to accommodate busy resident schedules and duty-hour restrictions. PD
perceptions of e-learning are relatively moderate and future research should
determine whether PD reluctance to adopt e-learning is based on unawareness of
the evidence, perceptions that e-learning is expensive, or judgments about value
versus effectiveness.
PMID- 28697745
TI - Using LMS tables to determine waist circumference and waist-to-height ratios in
Colombian children and adolescents: the FUPRECOL study.
AB - BACKGROUND: Waist circumference (WC) and waist-to-height ratio (WHtR) are often
used as indices predictive of central obesity. The aims of this study were: 1) to
obtain smoothed centile charts and LMS tables for WC and WHtR among Colombian
children and adolescents; 2) to evaluate the utility of these parameters as
predictors of overweight and obesity. METHOD: A cross-sectional study was
conducted of a sample population of 7954 healthy Colombian schoolchildren [3460
boys and 4494 girls, mean age 12.8 (+/-2.3) years]. Weight, height, body mass
index (BMI), WC and WHtR were measured, and percentiles were calculated using the
LMS method (Box-Cox, median and coefficient of variation). Appropriate cut-off
points of WC and WHtR for overweight and obesity, according to International
Obesity Task Force definitions, were selected using receiver operating
characteristic (ROC) analysis. The discriminating power of WC and WHtR is
expressed as area under the curve (AUC). RESULTS: Reference values for WC and
WHtR are presented. Mean WC increased and WHtR decreased with age for both
genders. A moderate positive correlation was observed between WC and BMI (r =
0.756, P < 0.01) and between WHtR and BMI (r = 0.604, P < 0.01). ROC analysis
revealed strong discrimination power in the identification of overweight and
obesity for both measures in our sample population. Overall, WHtR was a slightly
better predictor of overweight/obesity (AUC 95% CI 0.868-0.916) than WC (AUC 95%
CI 0.862-0.904). CONCLUSION: This paper presents the first sex and age-specific
WC and WHtR percentiles for Colombian children and adolescents aged 9.0-17.9
years. The LMS tables obtained, based on Colombian reference data, can be used as
quantitative tools for the study of obesity and its comorbidities.
PMID- 28697746
TI - Nursing & parental perceptions of neonatal care in Central Vietnam: a
longitudinal qualitative study.
AB - BACKGROUND: Neonatal mortality accounts for nearly three quarters of all infant
deaths in Vietnam. The nursing team are the largest professional group working
with newborns, however do not routinely receive neonatal training and there is a
lack of research into the impact of educational provision. This study explored
changes in nursing perceptions towards their role following a neonatal
educational intervention. Parents perceptions of nursing care were explored to
determine any changes as nurses gained more experience. METHOD: Semi-Structured
qualitative interviews were conducted every 6 months over an 18 month period with
16 nurses. At each time point, parents whose infant was resident on the neonatal
unit were invited to participate in an interview to explore their experiences of
nursing care. A total of 67 parents participated over 18 months. Interviews were
conducted and transcribed in Vietnamese before translation into English for
manifest content analysis facilitated by NVivo V14. RESULTS: Analysis of nursing
transcripts identified 14 basic categories which could be grouped (23) into 3
themes: (1) perceptions of the role of the neonatal nurse, (2) perception of the
parental role and (3) professional recollections. Analysis of parent transcripts
identified 14 basic categories which could be grouped into 3 themes: (1)
information sharing, (2) participation in care, and (3) personal experience.
CONCLUSIONS: Qualitative interviews highlighted the short term effect that the
introduction of an educational intervention can have on both nursing attitudes
towards and parental experience of care in one neonatal unit in central Vietnam.
Nurses shared a growing awareness of their role along with its ethical issues and
challenges, whilst parents discussed their overall desire for more participation
in their infants care. Further research is required to determine the long term
impact of the intervention, the ability of nurses to translate knowledge into
clinical practice through assessment of nursing knowledge and competence, and the
impact and needs of parents. A greater understanding will allow us to continue to
improve the experiences of nurses and parents, and highlight how these areas may
contribute towards the reduction of infant mortality and morbidity in Vietnam.
PMID- 28697747
TI - Exploring residents' experiences of mealtimes in care homes: A qualitative
interview study.
AB - BACKGROUND: Many interventions aim to alleviate well-documented problems of
malnutrition in residential care homes and improve residents' health and
wellbeing. Despite some positive findings, little is known about how and why
mealtime interventions might be effective, and in particular, what effects
residents' experiences of mealtimes have on health outcomes. The aim of this
study was to gain an insight into these experiences and explore some of the
issues that may impact on residents' enjoyment of meals, and resulting health and
wellbeing. METHODS: Semi-structured interviews were conducted with eleven
residents from four care homes in the South West UK. Thematic analysis was used
to derive content and meaning from transcribed interviews. Interviews were
supplemented by researcher observations of mealtimes. RESULTS: The dining
experience was a focal point for participants' broader experiences of residing in
a care home. Three themes pertaining to residents' experiences were identified:
(1) Emotional and psychological connections with other residents; (2) managing
competing interests with limited resources; and (3) familiarity and routine.
CONCLUSION: Mealtimes are a mainstay of life in a care home through which
residents' experiences are characterised, exemplified and magnified.
Understanding how residents interact with one another, accommodating their
preferences and encouraging autonomy may enhance their mealtime experiences. It
may also help to ease the transition from independent-living to life in care,
which can be particularly stressful for some residents, and improve health and
wellbeing over the long-term.
PMID- 28697748
TI - Endothelial progenitor cells transplantation attenuated blood-brain barrier
damage after ischemia in diabetic mice via HIF-1alpha.
AB - BACKGROUND: Blood-brain barrier impairment is a major indicator of endothelial
dysfunction in diabetes. Studies showed that endothelial progenitor cell (EPC)
transplantation promoted angiogenesis and improved function recovery after hind
limb ischemia in diabetic mice. The effect of EPC transplantation on blood-brain
barrier integrity after cerebral ischemia in diabetic animals is unknown. The aim
of this study is to explore the effect of EPC transplantation on the integrity of
the blood-brain barrier after cerebral ischemia in diabetic mice. METHODS: EPCs
were isolated by density gradient centrifugation and characterized by flow
cytometry and immunostaining. Diabetes was induced in adult male C57BL/6 mice by
a single injection of streptozotocin at 4 weeks before surgery. Diabetic mice
underwent 90-minute transient middle cerebral artery occlusion surgery and
received 1 * 106 EPCs transplantation immediately after reperfusion. Brain
infarct volume, blood-brain barrier permeability, tight junction protein
expression, and hypoxia inducible factor-1alpha (HIF-1alpha) mRNA level were
examined after treatment. RESULTS: We demonstrated that neurological deficits
were attenuated and brain infarct volume was reduced in EPC-transplanted diabetic
mice after transient cerebral ischemia compared to the controls (p < 0.05). Blood
brain barrier leakage and tight junction protein degradation were reduced in EPC
transplanted mice (p <0.05). EPCs upregulated HIF-1alpha expression while HIF
1alpha inhibitor PX-478 abolished the beneficial effect of EPCs. CONCLUSIONS: We
conclude that EPCs protected blood-brain barrier integrity after focal ischemia
in diabetic mice through upregulation of HIF-1alpha signaling.
PMID- 28697749
TI - Comparative genomic analysis of Acinetobacter strains isolated from murine
colonic crypts.
AB - BACKGROUND: A restricted set of aerobic bacteria dominated by the Acinetobacter
genus was identified in murine intestinal colonic crypts. The vicinity of such
bacteria with intestinal stem cells could indicate that they protect the crypt
against cytotoxic and genotoxic signals. Genome analyses of these bacteria were
performed to better appreciate their biodegradative capacities. RESULTS: Two
taxonomically different clusters of Acinetobacter were isolated from murine
proximal colonic crypts, one was identified as A. modestus and the other as A.
radioresistens. Their identification was performed through biochemical parameters
and housekeeping gene sequencing. After selection of one strain of each cluster
(A. modestus CM11G and A. radioresistens CM38.2), comparative genomic analysis
was performed on whole-genome sequencing data. The antibiotic resistance pattern
of these two strains is different, in line with the many genes involved in
resistance to heavy metals identified in both genomes. Moreover whereas the
operon benABCDE involved in benzoate metabolism is encoded by the two genomes,
the operon antABC encoding the anthranilate dioxygenase, and the phenol
hydroxylase gene cluster are absent in the A. modestus genomic sequence,
indicating that the two strains have different capacities to metabolize
xenobiotics. A common feature of the two strains is the presence of a type IV
pili system, and the presence of genes encoding proteins pertaining to secretion
systems such as Type I and Type II secretion systems. CONCLUSIONS: Our
comparative genomic analysis revealed that different Acinetobacter isolated from
the same biological niche, even if they share a large majority of genes, possess
unique features that could play a specific role in the protection of the
intestinal crypt.
PMID- 28697750
TI - Association of lifestyle and body structure to ocular axial length in Japanese
elementary school children.
AB - BACKGROUND: The purpose of this study is to determine whether the lifestyle and
body stature are significantly associated with the axial length (AL) of the eyes
of Japanese third grade students. METHODS: A prospective, cross sectional,
observational study was performed on 122 third grade students consisting of 61
boys and 61 girls ages 8 to 9 years. The AL, body height, body weight, and body
mass index (BMI) were measured. The lifestyle was determined by activities such
as the daily duration of indoor studying, television viewing, use of computers
and smart phones, outdoor activity time, bed time, Japanese or Western dietary
habits, and parental myopia were investigated by a questionnaire with three or
five grade levels. The relationship between AL and the questionnaire variables
were analyzed by Spearman's correlation analyses. RESULTS: Westernized dietary
habits (r = -0.24, P = 0.01), duration of computer and smart phone use (r = 0.24,
P = 0.008), parental myopia (r = 0.39, P < 0.001), body weight (r = 0.26, P =
0.005), and BMI (r = 0.23, P = 0.011) were significantly correlated with the AL.
Multiple logistic regression analyses showed that the sex [r = -0.48; 95%
confidence interval (CI) -0.80 to -0.17, P = 0.003], body weight (r = 0.04; 95%
CI 0.02 to 0.07, P = 0.038), westernized dietary habits (r = -0.30; 95% CI -0.55
to -0.05, P = 0.021), and parental myopia (r = 0.40; 95% CI 0.20 to 0.61, P <
0.001) were significantly and independently correlated with the AL. CONCLUSIONS:
The body weight and parental myopia and westernized dietary habits are factors
significantly associated with myopia. Changing from Japanese food style to
westernized food style might increase the risk of progression of school myopia.
PMID- 28697751
TI - Influence of functional dentition on satisfaction with oral health and impacts on
daily performance among Brazilian adults: a population-based cross-sectional
study.
AB - BACKGROUND: Dental esthetics, chewing and speech should be preserved in a
dentition denominated functional and are closely related to satisfaction with
oral health (SOH), impacts caused by oral problems and have a possible
association with Oral Health-Related Quality of Life. Thus, the purpose of the
present study was to investigate the influence of different concepts of
functional dentition (FD) on both SOH and impacts on daily performance (IDP)
among Brazilian adults. METHODS: A cross-sectional study was conducted with 9564
adults (35-44 years). SOH and IDP were evaluated using the Oral Impacts on Daily
Performance (OIDP) questionnaire. FD was considered based on four different
definitions: I-classification of the World Health Organization (FDWHO = >=20
teeth); II-well-distributed teeth (WDT = >=10 teeth in each arch); III-classified
by esthetics and occlusion (FDClass5 = sequential presence of one tooth in each
arch, >=10 teeth in each arch, 12 anterior teeth, >=three posterior occluding
pairs [POPs] of premolars and >=one POP molar bilaterally); and IV-classified by
esthetics, occlusion and periodontal status (FDClass6 = FDClass5 plus all
sextants with CPI <= 3 and/or CAL <= 1). The proportion of adults satisfied with
oral health and without overall impact (OIDP = 0) was calculated for each
definition of FD. Multiple Poisson regression models were adjusted by demographic
socioeconomic characteristics, self-reported oral problems and the use of dental
services for each dependent variable. RESULTS: When FDClass5 and FDClass6 were
considered a greater proportion of adults reported being satisfied (52.1 and
53.1%, respectively) and have OIDP = 0 (52.4 and 53.3, respectively). In the
multiple models, SOH was associated with FDClass5 (RP = 1.21) and FDClass6 (RP =
1.24) and OIDP = 0 was associated with WDT (RP = 1.14) and FDClass6 (RP = 1.21).
CONCLUSIONS: The greater influence of WDT, FDClass5 and FDClass6 on aspects
related to quality of life in comparison to FDWHO demonstrates the need for the
establishment of a broader definition of FD that encompasses subjective aspects.
PMID- 28697752
TI - Who is responsible for providing care? Investigating the role of care tasks and
past experiences in a cross-sectional survey in the Netherlands.
AB - BACKGROUND: Many countries face substitution from formal to informal care. It is
essential that a sufficient number of caregivers, such as family, friends or
neighbors, are willing and able to lend care to address the needs of ill or
elderly persons. We investigated whether the general public, who might become
caregivers in the future, and current informal caregivers align with the shift to
more informal caregiving. METHODS: We studied the views on the responsibility for
care of the general public versus the government, and whether these views
differed among groups with diverse past experiences with care in terms of own
health problems or previous caregiving activities. Data (n = 1097) was collected
among the Dutch Health Care Consumer Panel with a survey in October 2015.
Multivariate analyses of the views on responsibility for care in general and for
different types of care were performed using (i) health, (ii) informal care, and
(iii) general background characteristics, among a sample of the general public
and among a subgroup of current caregivers. RESULTS: The majority (67%) of the
respondents would be willing to provide informal care in the future, when
necessary. Respondents were more willing to provide support tasks than personal
or nursing care activities. Among current caregivers, views on responsibility for
care were associated with their past experience. Experiencing less burden of
caregiving was associated with perceiving the general public as more responsible
for personal or nursing care. CONCLUSIONS: The results of this study show that
substitution from formal to informal care is more in line with public views when
support activities are concerned than personal or nursing care. In addition,
burdened caregivers also consider the government more responsible for personal or
nursing care. When handing over care tasks to the public domain a critical view
is needed on which care tasks are most appropriate for this.
PMID- 28697753
TI - Integrated genomic analysis of biological gene sets with applications in lung
cancer prognosis.
AB - BACKGROUND: Burgeoning interest in integrative analyses has produced a rise in
studies which incorporate data from multiple genomic platforms. Literature for
conducting formal hypothesis testing on an integrative gene set level is
considerably sparse. This paper is biologically motivated by our interest in the
joint effects of epigenetic methylation loci and their associated mRNA gene
expressions on lung cancer survival status. RESULTS: We provide an efficient
screening approach across multiplatform genomic data on the level of biologically
related sets of genes, and our methods are applicable to various disease models
regardless whether the underlying true model is known (iTEGS) or unknown (iNOTE).
Our proposed testing procedure dominated two competing methods. Using our
methods, we identified a total of 28 gene sets with significant joint epigenomic
and transcriptomic effects on one-year lung cancer survival. CONCLUSIONS: We
propose efficient variance component-based testing procedures to facilitate the
joint testing of multiplatform genomic data across an entire gene set. The
testing procedure for the gene set is self-contained, and can easily be extended
to include more or different genetic platforms. iTEGS and iNOTE implemented in R
are freely available through the inote package at https://cran.r-project.org// .
PMID- 28697754
TI - Life behind the wall: sensing mechanical cues in plants.
AB - There is increasing evidence that all cells sense mechanical forces in order to
perform their functions. In animals, mechanotransduction has been studied during
the establishment of cell polarity, fate, and division in single cells, and
increasingly is studied in the context of a multicellular tissue. What about
plant systems? Our goal in this review is to summarize what is known about the
perception of mechanical cues in plants, and to provide a brief comparison with
animals.
PMID- 28697755
TI - Spread of resistant gram negatives in a Sri Lankan intensive care unit.
AB - BACKGROUND: Infections with multi drug resistant (MDR) organisms are a major
problem in intensive care units (ICUs). Proper infection control procedures are
mandatory to combat the spread of resistant organisms within ICUs. Well
stablished surveillance programmes will enhance the adherence of the staff to
infection control protocols. The study was conducted to assess the feasibility of
using basic molecular typing methods and routine hospital data for laboratory
surveillance of resistance organisms in resource limited settings. METHODS: A
retrospective study was conducted using consecutive Gram negative isolates
obtained from an ICU over a six month period. Antibiotic sensitivity patterns and
random amplified polymorphic DNA (RAPD) based typing was performed on the given
isolates. RESULTS: Of the seventy isolates included in the study, seven were
E.coli. All E.coli were MDRs and Extended Spectrum beta lactamse (ESBL) producers
carrying bla CTX-M. Fourteen isolates were K.pneumoniae, and all were MDRs and
ESBL producers. All K.pneumoniae harboured bla SHV while 13 harboured bla CTX-M.
The MDR rate among P.aeruginosa was 13% (n=15) while all acinetobacters (n=30)
were MDRs. Predominant clusters were identified within all four types of Gram
negatives using RAPD and the ICU stay of patients overlapped temporally.
CONCLUSION: We propose that simple surveillance methods like RAPD based typing
and basic hospital data can be used to convince hospital staff to adhere to
infection control protocols more effectively, in low and middle income countries.
PMID- 28697756
TI - Proteomic characterization of paired non-malignant and malignant African-American
prostate epithelial cell lines distinguishes them by structural proteins.
AB - BACKGROUND: While many factors may contribute to the higher prostate cancer
incidence and mortality experienced by African-American men compared to their
counterparts, the contribution of tumor biology is underexplored due to
inadequate availability of African-American patient-derived cell lines and
specimens. Here, we characterize the proteomes of non-malignant RC-77 N/E and
malignant RC-77 T/E prostate epithelial cell lines previously established from
prostate specimens from the same African-American patient with early stage
primary prostate cancer. METHODS: In this comparative proteomic analysis of RC-77
N/E and RC-77 T/E cells, differentially expressed proteins were identified and
analyzed for overrepresentation of PANTHER protein classes, Gene Ontology
annotations, and pathways. The enrichment of gene sets and pathway significance
were assessed using Gene Set Enrichment Analysis and Signaling Pathway Impact
Analysis, respectively. The gene and protein expression data of age- and stage
matched prostate cancer specimens from The Cancer Genome Atlas were analyzed.
RESULTS: Structural and cytoskeletal proteins were differentially expressed and
statistically overrepresented between RC-77 N/E and RC-77 T/E cells. Beta
catenin, alpha-actinin-1, and filamin-A were upregulated in the tumorigenic RC-77
T/E cells, while integrin beta-1, integrin alpha-6, caveolin-1, laminin subunit
gamma-2, and CD44 antigen were downregulated. The increased protein level of beta
catenin and the reduction of caveolin-1 protein level in the tumorigenic RC-77
T/E cells mirrored the upregulation of beta-catenin mRNA and downregulation of
caveolin-1 mRNA in African-American prostate cancer specimens compared to non
malignant controls. After subtracting race-specific non-malignant RNA expression,
beta-catenin and caveolin-1 mRNA expression levels were higher in African
American prostate cancer specimens than in Caucasian-American specimens. The "ECM
Receptor Interaction" and "Cell Adhesion Molecules", and the "Tight Junction" and
"Adherens Junction" pathways contained proteins are associated with RC-77 N/E and
RC-77 T/E cells, respectively. CONCLUSIONS: Our results suggest RC-77 T/E and RC
77 N/E cell lines can be distinguished by differentially expressed structural and
cytoskeletal proteins, which appeared in several pathways across multiple
analyses. Our results indicate that the expression of beta-catenin and caveolin-1
may be prostate cancer- and race-specific. Although the RC-77 cell model may not
be representative of all African-American prostate cancer due to tumor
heterogeneity, it is a unique resource for studying prostate cancer initiation
and progression.
PMID- 28697757
TI - Estimating Phred scores of Illumina base calls by logistic regression and sparse
modeling.
AB - BACKGROUND: Phred quality scores are essential for downstream DNA analysis such
as SNP detection and DNA assembly. Thus a valid model to define them is
indispensable for any base-calling software. Recently, we developed the base
caller 3Dec for Illumina sequencing platforms, which reduces base-calling errors
by 44-69% compared to the existing ones. However, the model to predict its
quality scores has not been fully investigated yet. RESULTS: In this study, we
used logistic regression models to evaluate quality scores from predictive
features, which include different aspects of the sequencing signals as well as
local DNA contents. Sparse models were further obtained by three methods: the
backward deletion with either AIC or BIC and the L 1 regularization learning
method. The L 1-regularized one was then compared with the Illumina scoring
method. CONCLUSIONS: The L 1-regularized logistic regression improves the
empirical discrimination power by as large as 14 and 25% respectively for two
kinds of preprocessed sequencing signals, compared to the Illumina scoring
method. Namely, the L 1 method identifies more base calls of high fidelity.
Computationally, the L 1 method can handle large dataset and is efficient enough
for daily sequencing. Meanwhile, the logistic model resulted from BIC is more
interpretable. The modeling suggested that the most prominent quenching pattern
in the current chemistry of Illumina occurred at the dinucleotide "GT". Besides,
nucleotides were more likely to be miscalled as the previous bases if the
preceding ones were not "G". It suggested that the phasing effect of bases after
"G" was somewhat different from those after other nucleotide types.
PMID- 28697758
TI - Identification of QTLs controlling grain protein concentration using a high
density SNP and SSR linkage map in barley (Hordeum vulgare L.).
AB - BACKGROUND: Grain protein concentration (GPC) is a major determinant of quality
in barley (Hordeum vulgare L.). Breeding barley cultivars with high GPC has
practical value for feed and food properties. The aim of the present study was to
identify quantitative trait loci (QTLs) for GPC that could be detected under
multiple environments. RESULTS: A population of 190 recombinant inbred lines
(RILs) deriving from a cross between Chinese landrace ZGMLEL with high GPC (>
20%) and Australian cultivar Schooner was used for linkage and QTL analyses. The
genetic linkage map spanned 2353.48 cM in length with an average locus interval
of 2.33 cM. GPC was evaluated under six environments for the RIL population and
the two parental lines. In total, six environmentally stable QTLs for GPC were
detected on chromosomes 2H (1), 4H (1), 6H (1), and 7H (3) and the increasing
alleles were derived from ZGMLEL. Notably, the three QTLs on chromosome 7H
(QGpc.ZiSc-7H.1, QGpc.ZiSc-7H.2, and QGpc.ZiSc-7H.3) that linked in coupling
phase were firstly identified. Moreover, the genetic effects of stable QTLs on
chromosomes 2H, 6H and 7H were validated using near isogenic lines (NILs).
CONCLUSIONS: Collectively, the identified QTLs expanded our knowledge about the
genetic basis of GPC in barley and could be selected to develop cultivars with
high grain protein concentration.
PMID- 28697759
TI - The distinct biological implications of Asxl1 mutation and its roles in
leukemogenesis revealed by a knock-in mouse model.
AB - BACKGROUND: Additional sex combs-like 1 (ASXL1) is frequently mutated in myeloid
malignancies. Recent studies showed that hematopoietic-specific deletion of Asxl1
or overexpression of mutant ASXL1 resulted in myelodysplasia-like disease in
mice. However, actual effects of a "physiological" dose of mutant ASXL1 remain
unexplored. METHODS: We established a knock-in mouse model bearing the most
frequent Asxl1 mutation and studied its pathophysiological effects on mouse
hematopoietic system. RESULTS: Heterozygotes (Asxl1 tm/+ ) marrow cells had
higher in vitro proliferation capacities as shown by more colonies in cobblestone
area forming assays and by serial re-plating assays. On the other hand, donor
hematopoietic cells from Asxl1 tm/+ mice declined faster in recipients during
transplantation assays, suggesting compromised long-term in vivo repopulation
abilities. There were no obvious blood diseases in mutant mice throughout their
life-span, indicating Asxl1 mutation alone was not sufficient for leukemogenesis.
However, this mutation facilitated engraftment of bone marrow cell overexpressing
MN1. Analyses of global gene expression profiles of ASXL1-mutated versus wild
type human leukemia cells as well as heterozygote versus wild-type mouse marrow
precursor cells, with or without MN1 overexpression, highlighted the association
of in vivo Asxl1 mutation to the expression of hypoxia, multipotent progenitors,
hematopoietic stem cells, KRAS, and MEK gene sets. ChIP-Seq analysis revealed
global patterns of Asxl1 mutation-modulated H3K27 tri-methylation in
hematopoietic precursors. CONCLUSIONS: We proposed the first Asxl1 mutation knock
in mouse model and showed mutated Asxl1 lowered the threshold of MN1-driven
engraftment and exhibited distinct biological functions on physiological and
malignant hematopoiesis, although it was insufficient to lead to blood
malignancies.
PMID- 28697760
TI - Hepatitis C bio-behavioural surveys in people who inject drugs-a systematic
review of sensitivity to the theoretical assumptions of respondent driven
sampling.
AB - BACKGROUND: New, more effective and better-tolerated therapies for hepatitis C
(HCV) have made the elimination of HCV a feasible objective. However, for this to
be achieved, it is necessary to have a detailed understanding of HCV epidemiology
in people who inject drugs (PWID). Respondent-driven sampling (RDS) can provide
prevalence estimates in hidden populations such as PWID. The aims of this
systematic review are to identify published studies that use RDS in PWID to
measure the prevalence of HCV, and compare each study against the STROBE-RDS
checklist to assess their sensitivity to the theoretical assumptions underlying
RDS. METHOD: Searches were undertaken in accordance with PRISMA systematic review
guidelines. Included studies were English language publications in peer-reviewed
journals, which reported the use of RDS to recruit PWID to an HCV bio-behavioural
survey. Data was extracted under three headings: (1) survey overview, (2) survey
outcomes, and (3) reporting against selected STROBE-RDS criteria. RESULTS: Thirty
one studies met the inclusion criteria. They varied in scale (range 1-15 survey
sites) and the sample sizes achieved (range 81-1000 per survey site) but were
consistent in describing the use of standard RDS methods including: seeds,
coupons and recruitment incentives. Twenty-seven studies (87%) either calculated
or reported the intention to calculate population prevalence estimates for HCV
and two used RDS data to calculate the total population size of PWID. Detailed
operational and analytical procedures and reporting against selected criteria
from the STROBE-RDS checklist varied between studies. There were widespread
indications that sampling did not meet the assumptions underlying RDS, which led
to two studies being unable to report an estimated HCV population prevalence in
at least one survey location. CONCLUSION: RDS can be used to estimate a
population prevalence of HCV in PWID and estimate the PWID population size.
Accordingly, as a single instrument, it is a useful tool for guiding HCV
elimination. However, future studies should report the operational conduct of
each survey in accordance with the STROBE-RDS checklist to indicate sensitivity
to the theoretical assumptions underlying the method. SYSTEMATIC REVIEW
REGISTRATION: PROSPERO CRD42015019245.
PMID- 28697761
TI - HLA-check: evaluating HLA data from SNP information.
AB - BACKGROUND: The major histocompatibility complex (MHC) region of the human
genome, and specifically the human leukocyte antigen (HLA) genes, play a major
role in numerous human diseases. With the recent progress of sequencing methods
(eg, Next-Generation Sequencing, NGS), the accurate genotyping of this region has
become possible but remains relatively costly. In order to obtain the HLA
information for the millions of samples already genotyped by chips in the past
ten years, efficient bioinformatics tools, such as SNP2HLA or HIBAG, have been
developed that infer HLA information from the linkage disequilibrium existing
between HLA alleles and SNP markers in the MHC region. RESULTS: In this study, we
first used ShapeIT and Impute2 to implement an imputation method akin to SNP2HLA
and found a comparable quality of imputation on a European dataset. More
importantly, we developed a new tool, HLA-check, that allows for the detection of
aberrant HLA allele calling with regard to the SNP genotypes in the region.
Adding this tool to the HLA imputation software increases dramatically their
accuracy, especially for HLA class I genes. CONCLUSION: Overall, HLA-check was
able to identify a limited number of implausible HLA typings (less than 10%) in a
population, and these samples can then either be removed or be retyped by NGS for
HLA association analysis.
PMID- 28697762
TI - Cash transfers for HIV prevention: what do young women spend it on? Mixed methods
findings from HPTN 068.
AB - BACKGROUND: Social grants have been found to have an impact on health and
wellbeing in multiple settings. Who receives the grant, however, has been the
subject of discussion with regards to how the money is spent and who benefits
from the grant. METHODS: Using survey data from 1214 young women who were in the
intervention arm and completed at least one annual visit in the HPTN 068 trial,
and qualitative interview data from a subset of 38 participants, we examined
spending of a cash transfer provided to young women conditioned on school
attendance. RESULTS: We found that spending was largely determined and controlled
by young women themselves and that the cash transfer was predominately spent on
toiletries, clothing and school supplies. In interview data, young women
discussed the significant role of cash transfers for adolescent identity,
specifically with regard to independence from family and status within the peer
network. There were almost no negative consequences from receiving the cash
transfer. CONCLUSIONS: We established that providing adolescents access to cash
was not reported to be associated with social harms or negative consequences.
Rather, spending of the cash facilitated appropriate adolescent developmental
behaviours. The findings are encouraging at a time in which there is global
interest in addressing the structural drivers of HIV risk, such as poverty, for
young women. TRIAL REGISTRATION: Clinicaltrials.gov NCT01233531 (1 Nov 2010).
First participant enrolled 5 March 2011.
PMID- 28697763
TI - Effect of neuroticism on risk of cardiovascular disease in depressed persons - a
Swedish population-based cohort study.
AB - BACKGROUND: The relationship between neuroticism, depression and cardiovascular
disease (CVD) is complex and has so far not been studied in depth. The aim of
this study was to determine if neuroticism is an effect-modifier in the
association between depression and CVD. Data derived from a longitudinal cohort
study on mental health, work and relations among adults (20-64 years), including
10,443 individuals. Depression was assessed using the Major Depression Inventory
(MDI) and neuroticism by the Swedish Scale of Personality (SSP). Outcomes of
cardiovascular disease were register-based from the National inpatient register.
RESULTS: Both depression (OR 1.9 (95%CI 1.4, 2.5)) and high levels of neuroticism
(OR 1.2 (95%CI 1.1-1.3)) were associated with increased risk of CVD. The combined
effect of depression and neuroticism on the risk of CVD revealed HRs ranging from
1.0 to 1.9 after adjusting for age and gender, socioeconomic position, prevalent
hypertension and diabetes. Almost similar associations were seen after further
adjustment for lifestyle factors. CONCLUSION: Neuroticism increased the risk of
CVD in depressed persons. We found synergistic interaction between neuroticism
and depression status in predicting future risk of CVD.
PMID- 28697765
TI - Deregulation of sale of over-the-counter drugs outside of pharmacies in the
Republic of Korea: interrupted-time-series analysis of outpatient visits before
and after the policy.
AB - BACKGROUND: We evaluated the effectiveness of a policy allowing for the sale of
over-the-counter drugs outside of pharmacies by examining its effect on number of
monthly outpatient visits for acute upper respiratory infections, dyspepsia, and
migraine. METHOD: We used medical claims data extracted from the Korean National
Health Insurance Cohort Database from 2009 to 2013. The Korean National Health
Insurance Cohort Database comprises a nationally representative sample of claims
about 2% of the entire population - obtained from the medical record data held
by the Korean National Health Insurance Corporation (which has data on the entire
nation). The analysis included26,284,706 person-months of 1,042,728 individuals.
An interrupted-time series analysis was performed. Outcome measures were monthly
outpatient visits for acute upper respiratory infections, dyspepsia, and
migraine. To investigate the effect of the policy, we compared the number of
monthly visits before and after the policy's implementation in 2012. RESULT: For
acute upper respiratory infections, monthly outpatient visits showed a decreasing
trend before the policy (beta = -0.0003);after it, a prompt change and increasing
trend in monthly outpatient visits were observed, but these were non-significant.
For dyspepsia, the trend was increasing before implementation (beta = -0.0101),
but this reversed after implementation(beta = -0.007). For migraine, an
increasing trend was observed before the policy (beta = 0.0057). After it, we
observed a significant prompt change (beta = -0.0314) but no significant trend.
CONCLUSION: Deregulation of selling over-the-counter medication outside of
pharmacies reduced monthly outpatient visits for dyspepsia and migraine symptoms,
but not acute upper respiratory infections.
PMID- 28697764
TI - Long non-coding RNA linc00673 regulated non-small cell lung cancer proliferation,
migration, invasion and epithelial mesenchymal transition by sponging miR-150-5p.
AB - BACKGROUND: The function of a new long non-coding RNA linc00673 remains unclear.
While identified as an oncogenic player in non-small cell lung cancer (NSCLC),
linc00673 was found to be anti-oncogenic in pancreatic ductal adenocarcinoma
(PDAC). However whether linc00673 regulated malignancy and epithelial mesenchymal
transition (EMT) has not been characterized. METHODS: Cell proliferation was
assessed using CCK-8 and EdU assays, and cell migration and invasion were
assessed using scratch assays and transwell invasion assays. Epithelial
mesenchymal transition was examined using western blot, qRT-PCR and
immunofluorescence staining. Interaction between miRNA and linc00673 was
determined using luciferase reporter assays. In vivo experiments were performed
to assess tumor formation. In addition, the expression data of NSCLC specimens of
TCGA and patient survival data were utilized to explore the prognostic
significance of linc00673. RESULTS: In the present study, we found high linc00673
expression was associated with poor prognosis of NSCLC patients. In vitro
experiments showed linc00673 knockdown reversed TGF-beta induced EMT, and miR-150
5p was predicted to target linc00673 through bioinformatics tools. Overexpression
of miR-150-5p suppressed lin00673's expression while inhibition of miR-150-5p led
to significant upregulation of lin00673, suggesting that linc00673 could be
negatively regulated by miR-150-5p, which was further confirmed by the inverse
correlation between linc00673 and miR-150-5p in NSCLC patients' specimen.
Furthermore, we proved that miR-150-5p could directly target linc00673 through
luciferase assay, so linc00673 could sponge miR-150-5p and modulate the
expression of a key EMT regulator ZEB1 indirectly. In addition, miR-150-5p
inhibition abrogated linc00673 silence mediated proliferation, migration,
invasion and EMT suppressing effect. Moreover, the inhibition of linc00673
significantly attenuated the tumorigenesis ability of A549 cells in vivo.
CONCLUSIONS: We validated linc00673 as a novel oncogenic lncRNA and demonstrated
the molecular mechanism by which it promotes NSCLC, which will advance our
understanding of its clinical significance.
PMID- 28697766
TI - Developing a core outcome set for chronic rhinosinusitis: a systematic review of
outcomes utilised in the current literature.
AB - BACKGROUND: A core outcome set (COS) is an agreed standardised collection of
outcomes that should be measured and reported by all trials for a specific
clinical area, in this case chronic rhinosinusitis. These are not restrictive and
researchers may continue to explore other outcomes alongside these that they feel
are relevant to their intervention. The aim of this systematic review was to
identify the need for a COS for chronic rhinosinusitis. METHODS: A sensitive
search strategy was used to identify all published Cochrane systematic reviews
and randomised control trials of intervention for adult patients with chronic
rhinosinusitis. Two independent authors reviewed these to obtain a list of
outcomes and outcome measures reported by each clinical trial. RESULTS: Sixty
nine randomised control trials and eight Cochrane systematic reviews were
included in this study. They reported 68 individual outcomes and outcome
measures, with an average of four to ten outcomes per clinical trial. These
outcomes were mapped to 23 subcategories belonging to eight core categories.
CONCLUSIONS: The key finding of this review was the heterogeneity of outcomes
reported and measured by clinical trials of patients with chronic rhinosinusitis,
precluding meaningful meta-analysis of data. This review supports the need for
development of a COS, to be used in future trials on adult patients with chronic
rhinosinusitis.
PMID- 28697767
TI - The impact of the time of drug administration on the effectiveness of combined
treatment of hypercholesterolemia with Rosuvastatin and Ezetimibe (RosEze): study
protocol for a randomized controlled trial.
AB - BACKGROUND: Hypercholesterolemia is one of the main risk factors for
cardiovascular disease. The first line treatment for hypercholesterolemia is
statin therapy. When the expected low-density lipoprotein cholesterol (LDL-C)
concentration is not achieved, the pharmacotherapy may be extended by combining
the statin with the cholesterol absorption inhibitor ezetimibe. METHODS/DESIGN:
The study is designed as a randomized, open-label, single-center, crossover study
evaluating the effectiveness of combined therapy with rosuvastatin and ezetimibe
for hypercholesterolemia. The study is planned to include 200 patients with
hypercholesterolemia ineffectively treated with statins for at least 6 weeks.
After enrollment participants are randomized into one of two arms receiving
rosuvastatin and ezetimibe. In the first arm the study drug is administered in
the morning (8:00 am) for 6 weeks and then in the evening for the next 6 weeks;
in the second arm the study drug is administered at first in the evening (8:00
pm) for the first 6 weeks and then in the morning for the following 6 weeks. In
order to minimize non-adherence to the treatment, all patients will receive the
study drug free of charge. The primary outcome of the study is change in LDL-C at
6 and 12 weeks of the treatment, depending on the time of day of study drug
administration. The secondary endpoints include change in total cholesterol, high
density lipoprotein (HDL) cholesterol, triglycerides, apolipoproteins ApoB and
Apo AI, non-HDL cholesterol, small, dense (sd)-LDL cholesterol, lipoprotein(a),
glucose, glycated hemoglobin, high-sensitivity C-reactive protein, aspartate
aminotransferase, alanine aminotransferase, gamma-glutamyl transferase, and
creatine kinase at 6 and 12 weeks of the study drug treatment, as well as
assessment of plasma fluorescence using stationary and time-resolved fluorescence
spectroscopy at baseline and at 6 and 12 weeks of the therapy. DISCUSSION: The
RosEze trial is expected to demonstrate whether there is a significant difference
in the effectiveness of the lipid-lowering therapy in reducing the concentration
of cholesterol when the medications are taken in the morning compared with the
evening time of day. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02772640 .
Registered on 28 March 2016.
PMID- 28697768
TI - Identifying inequitable healthcare in older people: systematic review of current
research practice.
AB - BACKGROUND: There is growing consensus on the importance of identifying age
related inequities in the receipt of public health and healthcare interventions,
but concerns regarding conceptual and methodological rigour in this area of
research. Establishing age inequity in receipt requires evidence of a difference
that is not an artefact of poor measurement of need or receipt; is not warranted
on the grounds of patient preference or clinical safety; and is judged to be
unfair. METHOD: A systematic, thematic literature review was undertaken with the
objective of characterising recent research approaches. Studies were eligible if
the population was in a country within the Organisation for Economic Co-operation
and Development and analyses included an explicit focus on age-related patterns
of healthcare receipt including those 60 years or older. A structured extraction
template was applied. Extracted material was synthesised in thematic memos. A set
of categorical codes were then defined and applied to produce summary counts
across key dimensions. This process was iterative to allow reconciliation of
discrepancies and ensure reliability. RESULTS: Forty nine studies met the
eligibility criteria. A wide variety of concepts, terms and methodologies were
used across these studies. Thirty five studies employed multivariable techniques
to produce adjusted receipt-need ratios, though few clearly articulated their
rationale, indicating the need for great conceptual clarity. Eighteen studies
made reference to patient preference as a relevant consideration, but just one
incorporated any kind of adjustment for this factor. Twenty five studies
discussed effectiveness among older adults, with fourteen raising the possibility
of differential effectiveness, and one differential cost-effectiveness, by age.
Just three studies made explicit reference to the ethical nature of healthcare
resource allocation by age. While many authors presented suitably cautious
conclusions, some appeared to over-stretch their findings concluding that
observed differences were 'inequitable'. Limitations include possible biases in
the retrieved material due to inconsistent database indexing and a focus on OECD
country populations and studies with English titles. CONCLUSIONS: Caution is
needed among clinicians and other evidence-users in accepting claims of
healthcare 'ageism' in some published papers. Principles for improved research
practice are proposed.
PMID- 28697769
TI - A nurse-delivered, clinic-based intervention to address intimate partner violence
among low-income women in Mexico City: findings from a cluster randomized
controlled trial.
AB - BACKGROUND: Rigorous evaluations of health sector interventions addressing
intimate partner violence (IPV) in low- and middle-income countries are lacking.
We aimed to assess whether an enhanced nurse-delivered intervention would reduce
IPV and improve levels of safety planning behaviors, use of community resources,
reproductive coercion, and mental quality of life. METHODS: We randomized 42
public health clinics in Mexico City to treatment or control arms. In treatment
clinics, women received the nurse-delivered session (IPV screening, supportive
referrals, health/safety risk assessments) at baseline (T1), and a booster
counselling session after 3 months (T2). In control clinics, women received
screening and a referral card from nurses. Surveys were conducted at T1, T2, and
T3 (15 months from baseline). Our main outcome was past-year physical and sexual
IPV. Intent-to-treat analyses were conducted via three-level random intercepts
models to evaluate the interaction term for treatment status by time. RESULTS:
Between April and October 2013, 950 women (480 in control clinics, 470 in
treatment clinics) with recent IPV experiences enrolled in the study. While
reductions in IPV were observed for both women enrolled in treatment (OR, 0.40;
95% CI, 0.28-0.55; P < 0.01) and control (OR, 0.51; 95% CI, 0.36-0.72; P < 0.01)
clinics at T3 (July to December 2014), no significant treatment effects were
observed (OR, 0.78; 95% CI, 0.49-1.24; P = 0.30). At T2 (July to December 2013),
women in treatment clinics reported significant improvements, compared to women
in control clinics, in mental quality of life (beta, 1.45; 95% CI, 0.14-2.75; P =
0.03) and safety planning behaviors (beta, 0.41; 95% CI, 0.02-0.79; P = 0.04).
CONCLUSION: While reductions in IPV levels were seen among women in both
treatment and control clinics, the enhanced nurse intervention was no more
effective in reducing IPV. The enhanced nursing intervention may offer short-term
improvements in addressing safety planning and mental quality of life. Nurses can
play a supportive role in assisting women with IPV experiences. TRIAL
REGISTRATION: Clinicaltrials.gov ( NCT01661504 ). Registration Date: August 2,
2012.
PMID- 28697770
TI - Local professionals' perceptions of health assets in a low-SES Dutch
neighbourhood: a qualitative study.
AB - BACKGROUND: Asset-based approaches have become popular in public health. As yet
it is not known to what extent health and welfare professionals are able to
identify and mobilise individual and community health assets. Therefore, the aim
of this study was to understand professional's perceptions of health and health
assets. METHODS: In a low-SES neighbourhood, 21 health and welfare professionals
were interviewed about their definition of health and their perceptions of the
residents' health status, assets available in the neighbourhood's environment,
and the way residents use these assets. A Nominal Group Technique (NGT) session
was conducted for member check. Verbatim transcripts of the semi-structured
interviews were coded and analysed using Atlas.ti. RESULTS: The professionals
used a broad health concept, emphasizing the social dimension of health as most
important. They discussed the poor health of residents, mentioning multiple
health problems and unmet health needs. They provided many examples of behaviour
that they considered unhealthy, in particular unhealthy diet and lack of
exercise. Professionals considered the green physical environment, as well as
health and social services, including their own services, as important health
enhancing factors, whereas social and economic factors were considered as major
barriers for good health. Poor housing and litter in public space were considered
as barriers as well. According to the professionals, residents underutilized
neighbourhood health assets. They emphasised the impact of poverty on the
residents and their health. Moreover, they felt that residents were lacking
individual capabilities to lead a healthy life. Although committed to the
wellbeing of the residents, some professionals seemed almost discouraged by the
(perceived) situation. They looked for practical solutions by developing group
based approaches and supporting residents' self-organisation. CONCLUSIONS: Our
study shows, firstly, that professionals in the priority district Slotermeer
rated the health of the residents as poor and their health behaviour as
inadequate. They considered poverty and lack of education as important causes of
this situation. Secondly, the professionals tended to talk about barriers in the
neighbourhood rather than about neighbourhood health assets. As such, it seems
challenging to implement asset-based approaches. However, the professionals,
based on their own experiences, did perceive the development of collective
approaches as a promising direction for future community health development.
PMID- 28697771
TI - Evaluation of the safety and efficiency of novel metallic implant scaler tips
manufactured by the powder injection molding technique.
AB - BACKGROUND: Although many studies have compared the properties of ultrasonic
scaling instruments, it remains controversial as to which is most suitable for
implant scaling. This study evaluated the safety and efficiency of novel metallic
ultrasonic scaler tips made by the powder injection molding (PIM) technique on
titanium surfaces. METHODS: Mechanical instrumentation was carried out using four
types of metal scaler tips consisting of copper (CU), bronze (BR), 316 L
stainless steel (316 L), and conventional stainless steel (SS) tips. The
instrumented surface alteration image of samples was viewed with scanning
electron microscope (SEM) and surface profile of the each sample was investigated
with confocal laser scanning microscopy (CLSM). Arithmetic mean roughness (Ra)
and maximum height roughness (Rmax) of titanium samples were measured and
dissipated power of the scaler tip was estimated for scaling efficiency. RESULTS:
The average Ra values caused by the 316 L and SS tip were about two times higher
than those of the CU and BR tips (p < 0.05). The Rmax value showed similar
results. The efficiency of the SS tip was about 3 times higher than that of CU
tip, the 316 L tip is about 2.7 times higher than that of CU tip, and the BR tip
is about 1.2 times higher than that of CU tip. CONCLUSIONS: Novel metallic bronze
alloy ultrasonic scaler tip minimally damages titanium surfaces, similar to
copper alloy tip. Therefore, this bronze alloy scaler tip may be promising
instrument for implant maintenance therapy.
PMID- 28697772
TI - Injectable and compression-resistant low-viscosity polymer/ceramic composite
carriers for rhBMP-2 in a rabbit model of posterolateral fusion: a pilot study.
AB - BACKGROUND: The challenging biological and mechanical environment of
posterolateral fusion (PLF) requires a carrier that spans the transverse
processes and resists the compressive forces of the posterior musculature. The
less traumatic posterolateral approach enabled by minimally invasive surgical
techniques has prompted investigations into alternative rhBMP-2 carriers that are
injectable, settable, and compression-resistant. In this pilot study, we
investigated injectable low-viscosity (LV) polymer/composite bone grafts as
compression-resistant carriers for rhBMP-2 in a single-level rabbit PLF model.
METHODS: LV grafts were augmented with ceramic microparticles: (1) hydrolytically
degradable bioactive glass (BG), or (2) cell-degradable 85% beta-tricalcium
phosphate/15% hydroxyapatite (CM). Material properties, such as pore size,
viscosity, working time, and bulk modulus upon curing, were measured for each LV
polymer/ceramic material. An in vivo model of posterolateral fusion in a rabbit
was used to assess the grafts' capability to encourage spinal fusion. RESULTS:
These materials maintained a working time between 9.6 and 10.3 min, with a final
bulk modulus between 1.2 and 3.1 MPa. The LV polymer/composite bone grafts
released 55% of their rhBMP-2 over a 14-day period. As assessed by manual
palpation in vivo, fusion was achieved in all (n = 3) animals treated with LV/BG
or LV/CM carriers incorporating 430 MUg rhBMP-2/ml. Images of MUCT and
histological sections revealed evidence of bone fusion near the transverse
processes. CONCLUSION: This study highlights the potential of LV grafts as
injectable and compression-resistant rhBMP-2 carriers for posterolateral spinal
fusion.
PMID- 28697773
TI - Efficacy and safety of electroacupuncture in acute decompensated heart failure: a
study protocol for a randomized, patient- and assessor-blinded, sham controlled
trial.
AB - BACKGROUND: The purpose of this trial is to evaluate the effectiveness and safety
of electroacupuncture in the treatment of acute decompensated heart failure
compared with sham electroacupuncture. METHODS: This protocol is for a
randomized, sham controlled, patient- and assessor-blinded, parallel group,
single center clinical trial that can overcome the limitations of previous trials
examining acupuncture and heart failure. Forty-four acute decompensated heart
failure patients admitted to the cardiology ward will be randomly assigned into
the electroacupuncture treatment group (n = 22) or the sham electroacupuncture
control group (n = 22). Participants will receive electroacupuncture treatment
for 5 days of their hospital stay. The primary outcome of this study is the
difference in total diuretic dose between the two groups during hospitalization.
On the day of discharge, follow-up heart rate variability, routine blood tests,
cardiac biomarkers, high-sensitivity C-reactive protein (hs-CRP) level, and N
terminal pro b-type natriuretic peptide (NT-pro BNP) level will be assessed. Four
weeks after discharge, hs-CRP, NT-pro BNP, heart failure symptoms, quality of
life, and a pattern identification questionnaire will be used for follow-up
analysis. Six months after discharge, major cardiac adverse events and cardiac
function measured by echocardiography will be assessed. Adverse events will be
recorded during every visit. DISCUSSION: The result of this clinical trial will
offer evidence of the effectiveness and safety of electroacupuncture for acute
decompensated heart failure. TRIAL REGISTRATION: Clinical Research Information
Service: KCT0002249 .
PMID- 28697774
TI - The impact of DPP-4 inhibitors on long-term survival among diabetic patients
after first acute myocardial infarction.
AB - BACKGROUND: Previous studies regarding the cardioprotective effects of dipeptidyl
peptidase 4 (DPP-4) inhibitors have not provided sufficient evidence of a
relationship between DPP-4 inhibition and actual cardiovascular outcomes. This
study aimed to evaluate the impact of DPP-4 inhibitors on the survival of
diabetic patients after first acute myocardial infarction (AMI). METHODS: This
was a nationwide, propensity score-matched, case-control study of 186,112 first
AMI patients, 72,924 of whom had diabetes. A propensity score, one-to-one
matching technique was used to match 2672 controls to 2672 patients in the DPP-4
inhibitor group for analysis. Controls were matched based on gender, age, and a
history of hypertension, dyslipidemia, diabetes, peripheral vascular disease,
heart failure, cerebrovascular accident, end-stage renal disease, chronic
obstructive pulmonary disease, and percutaneous coronary intervention. RESULTS:
DPP-4 inhibitors improve the overall 3-year survival rate (log rank P < 0.0001),
whether male or female. Cox proportional hazard regression showed DPP-4 inhibitor
is beneficial in diabetes patients after AMI (HR = 0.86; 95% CI 0.78-0.95),
especially in those patients with hypertension (HR = 0.87; 95% CI 0.78-0.97; P =
0.0103) and cerebrovascular disease (HR = 0.83; 95% CI 0.72-0.97; P = 0.018), but
without dyslipidemia (HR = 0.78; 95% CI 0.67-0.92; P = 0.0029), without
peripheral vascular disease (HR = 0.86; 95% CI 0.78-0.96; P = 0.0047), without
heart failure (HR = 0.84; 95% CI 0.73-0.96; P = 0.0106), without end stage renal
disease (HR = 0.86; 95% CI 0.77-0.95; P = 0.0035), and without chronic
obstructive pulmonary disease (HR = 0.87; 95% CI 0.78-0.97; P = 0.0096).
CONCLUSIONS: DPP-4 inhibitor therapy improved long-term survival in diabetic
patients after first AMI, regardless of gender.
PMID- 28697775
TI - The relationship between vitamin D receptor gene polymorphism and deciduous tooth
decay in Chinese children.
AB - BACKGROUND: In the present study, we explored the link between vitamin D receptor
(VDR) BsmI, TaqI, ApaI and FokI gene polymorphisms with deciduous tooth decay in
Chinese children. METHODS: Our study included 380 Chinese children aged 4-7
years, whose DNA sample was collected from the buccal mucosa. VDR gene
polymorphisms was determined by PCR-RFLP. RESULTS: The adjusted logistic
regression analysis demonstrated that BsmI containing the Bb genotype was linked
with the increased risk of deciduous tooth decay (OR = 1.856, 95% CI = [1.184,
2.908], p = 0.007). However, VDR polymorphisms ApaI, TaqI and FokI were not
associated with deciduous tooth decay (ApaI: OR = 0.839, 95% CI = [0.614, 1.145],
p = 0.268; TaqI: OR = 1.150, 95% CI = [0.495, 2.672], p = 0.744; FokI: OR =
0.856, 95% CI = [0.616, 1.191], p = 0.356). CONCLUSIONS: Our results showed that
VDR BsmI polymorphism was associated with the risk of deciduous tooth decay in
Chinese children aged 4-7 years. However, the specific mechanism remains to
further verify through experiment.
PMID- 28697776
TI - Exposure to blue light during lunch break: effects on autonomic arousal and
behavioral alertness.
AB - BACKGROUND: Exposures to melanopsin-stimulating (melanopic) component-rich blue
light enhance arousal level. We examined their effects in office workers. Eight
healthy university office workers were exposed to blue and orange lights for 30
min during lunch break on different days. We compared the effects of light color
on autonomic arousal level assessed by heart rate variability (HRV) and
behavioral alertness by psychomotor vigilance tests (PVT). Heart rate was higher
and high-frequency (HF, 0.150.45 Hz) power of HRV was lower during exposure to
the blue light than to orange light. No significant difference with light color
was observed, however, in any HRV indices during PVT or in PVT performance after
light exposure. SHORT CONCLUSION: Exposure to blue light during lunch break,
compared with that to orange light, enhances autonomic arousal during exposure,
but has no sustained effect on autonomic arousal or behavioral alertness after
exposure.
PMID- 28697777
TI - Enhancing the use of research in health-promoting, anti-racism policy.
AB - BACKGROUND: The Localities Embracing and Accepting Diversity (LEAD) programme was
established to improve the health of ethnic minority communities through the
reduction of racial discrimination. Local governments in the state of Victoria,
Australia, were at the forefront of LEAD implementation in collaboration with
leading state and national organisations. Key aims included expanding the
available evidence regarding effective anti-racism interventions and facilitating
the uptake of this evidence in organisational policies and practices. METHODS:
One rural and one metropolitan local government areas were selected to
participate in LEAD. Key informant interviews and discussions were conducted with
individuals who had participated in LEAD implementation and members of LEAD
governance structures. Data were also collected on programme processes and
implementation, partnership formation and organisational assessments. RESULTS:
The LEAD model demonstrated both strengths and weaknesses in terms of
facilitating the use of evidence in a complex, community-based health promotion
initiative. Representation of implementing, funding and advisory bodies at
different levels of governance enabled the input of technical advice and guidance
alongside design and implementation. The representation structure assisted in
ensuring the development of a programme that was acceptable to all partners and
informed by the best available evidence. Simultaneous evaluation also enhanced
perceived validity of the intervention, allowed for strategy correction when
necessary and supported the process of double-loop organisational learning.
However, due to the model's demand for simultaneous and intensive effort by
various organisations, when particular elements of the intervention were not
functional, there was a considerable loss of time and resources across the
partner organisations. The complexity of the model also presented a challenge in
ensuring clarity regarding roles, functions and the direction of the programme.
CONCLUSIONS: The example of LEAD provides guidance on mechanisms to strengthen
the entry of evidence into complex community-based health promotion programmes.
The paper highlights some of the strengths and weaknesses of the LEAD model and
implications for practical collaboration between policymakers, implementers and
researchers.
PMID- 28697778
TI - Electrical impedance tomography for predicting failure of spontaneous breathing
trials in patients with prolonged weaning.
AB - BACKGROUND: Spontaneous breathing trials (SBTs) on a T-piece can be difficult in
patients with prolonged weaning because of remaining de-recruitment phenomena
and/or insufficient ventilation. There is no clinically established method
existent other than experience for estimating whether an SBT is most probably
beneficial. Electrical impedance tomography (EIT) is a clinical useful online
monitoring technique during mechanical ventilation, particularly because it
enables analysis of effects of regional ventilation distribution. The aim of our
observational study was to examine if EIT can predict whether patients with
prolonged weaning will benefit from a planned SBT. METHODS: Thirty-one patients
were examined. Blood gas analysis, vital parameter measurements, and EIT
recordings were performed at three time points: (1) baseline with pressure
support ventilation (PSV) (t0), (2) during a T-piece trial (t1), and (3) after
resumption of PSV (t2). Calculation of EIT parameters was performed, including
the impedance ratio (IR), the tidal variation of impedance (TIV), the changes in
end-expiratory lung impedance (DeltaEELI), the global inhomogeneity index (GI),
and the regional ventilation delay (RVD) index with use of different thresholds
of the percentage inspiration time (RVD40, RVD60, RVD80). The predictive power of
the baseline GI with regard to clinical impairment of an SBT was analyzed by
means of ROC curves. Clinical deterioration was assumed when tidal volume was
decreased by at least 20 ml after the T-piece trial, measured at t2. RESULTS:
Partial pressure of arterial oxygen significantly decreased at t1 (71 +/- 15
mmHg) compared with t0 (85 +/- 17 mmHg, p < 0.05) and t2 (82 +/- 18 mmHg, p <
0.05). The IR trended toward higher values during t1. At t1, TIV and DeltaEELI
significantly decreased. The GI was significantly increased at t1 (t0 59.3 +/-
46.1 vs t1 81.5 +/- 62.5, p = 0.001), as were all RVD indexes. Assuming a GI
cutoff value of >40, sensitivity of 85% and specificity of 50% were reached for
predicting an increased future tidal volume. CONCLUSIONS: EIT enables monitoring
of regional ventilation distribution during SBTs and is suitable to estimate
whether an SBT probably will be beneficial for an individual patient. Therefore,
the application of EIT can support clinical decisions regarding patients in the
phase of prolonged weaning.
PMID- 28697779
TI - Ethical, social, and cultural issues related to clinical genetic testing and
counseling in low- and middle-income countries: protocol for a systematic review.
AB - BACKGROUND: There has been little focus in the literature on how to build genetic
testing and counseling services in low- and middle-income countries in a
responsible, ethical, and culturally appropriate manner. It is unclear to what
extent this area is being explored and what form further research should take.
The proposed knowledge synthesis aims to fill this gap in knowledge and mine the
existing data to determine the breadth of work in this area and identify ethical,
social, and cultural issues that have emerged. METHODS/DESIGN: An integrated
knowledge translation approach will be undertaken by engaging knowledge users
throughout the review to ensure relevance to their practice. Electronic databases
encompassing various disciplines, such as healthcare, social sciences, and public
health, will be searched. Studies that address clinical genetic testing and/or
counseling and ethical, social, and/or cultural issues of these genetic services,
and are performed in low- and middle-income countries as defined by World Bank
will be considered for inclusion. Two independent reviewers will be involved in a
two-stage literature screening process, data extraction, and quality appraisal.
Studies included in the review will be analyzed by thematic analysis. A narrative
synthesis guided by the social ecological model will be used to summarize
findings. DISCUSSION: This systematic review will provide a foundation of
evidence regarding ethical, social, and cultural issues related to clinical
genetic testing and counseling in low- and middle-income countries. Using the
social ecological model as a conceptual framework will facilitate the
understanding of broader influences of the sociocultural context on an
individual's experience with clinical genetic testing and counseling, thereby
informing interdisciplinary sectors in future recommendations for practice and
policy. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42016042894.
PMID- 28697780
TI - Local infiltration of analgesia and sciatic nerve block provide similar pain
relief after total knee arthroplasty.
AB - BACKGROUND: Although femoral nerve block provides satisfactory analgesia after
total knee arthroplasty (TKA), residual posterior knee pain may decrease patient
satisfaction. We conducted a randomized controlled trial to clarify the efficacy
of the sciatic nerve block (SNB) and local infiltration of analgesia with steroid
(LIA) regarding postoperative analgesia after TKA, when administrated in addition
to femoral nerve block (FNB). METHODS: Seventy-eight patients were randomly
allocated to the two groups: concomitant administration of FNB and SNB or FNB and
LIA. The outcome measures included post-operative pain, passive knee motion, C
reactive protein level, time to achieve rehabilitation goals, the Knee Society
Score at the time of discharge, patient satisfaction level with anesthesia,
length of hospital stay, surgical time, and complications related to local
anesthesia. RESULTS: The patients in group SNB showed less pain than group LIA
only on postoperative hours 0 and 3. Satisfactory postoperative analgesia after
TKA was also achieved with LIA combined with FNB, while averting the risks
associated with SNB. The influence on progress of rehabilitation and length of
hospital stay was similar for both anesthesia techniques. CONCLUSIONS: The LIA
offers a potentially safer alternative to SNB as an adjunct to FNB, particularly
for patients who have risk factors for sciatic nerve injury.
PMID- 28697781
TI - Erratum to Statistical analysis plan for the Laser-1st versus Drops-1st for
Glaucoma and Ocular Hypertension Trial (LiGHT): a multi-centre randomised
controlled trial.
PMID- 28697782
TI - Exploring intentions of physician-scientist trainees: factors influencing MD and
MD/PhD interest in research careers.
AB - BACKGROUND: Prior studies have described the career paths of physician-scientist
candidates after graduation, but the factors that influence career choices at the
candidate stage remain unclear. Additionally, previous work has focused on
MD/PhDs, despite many physician-scientists being MDs. This study sought to
identify career sector intentions, important factors in career selection, and
experienced and predicted obstacles to career success that influence the career
choices of MD candidates, MD candidates with research-intense career intentions
(MD-RI), and MD/PhD candidates. METHODS: A 70-question survey was administered to
students at 5 academic medical centers with Medical Scientist Training Programs
(MSTPs) and Clinical and Translational Science Awards (CTSA) from the NIH. Data
were analyzed using bivariate or multivariate analyses. RESULTS: More MD/PhD and
MD-RI candidates anticipated or had experienced obstacles related to balancing
academic and family responsibilities and to balancing clinical, research, and
education responsibilities, whereas more MD candidates indicated experienced and
predicted obstacles related to loan repayment. MD/PhD candidates expressed higher
interest in basic and translational research compared to MD-RI candidates, who
indicated more interest in clinical research. Overall, MD-RI candidates displayed
a profile distinct from both MD/PhD and MD candidates. CONCLUSIONS: MD/PhD and MD
RI candidates experience obstacles that influence their intentions to pursue
academic medical careers from the earliest training stage, obstacles which differ
from those of their MD peers. The differences between the aspirations of and
challenges facing MD, MD-RI and MD/PhD candidates present opportunities for
training programs to target curricula and support services to ensure the career
development of successful physician-scientists.
PMID- 28697783
TI - Validation of QTL mapping and transcriptome profiling for identification of
candidate genes associated with nitrogen stress tolerance in sorghum.
AB - BACKGROUND: Quantitative trait loci (QTLs) detected in one mapping population may
not be detected in other mapping populations at all the time. Therefore, before
being used for marker assisted breeding, QTLs need to be validated in different
environments and/or genetic backgrounds to rule out statistical anomalies. In
this regard, we mapped the QTLs controlling various agronomic traits in a
recombinant inbred line (RIL) population in response to Nitrogen (N) stress and
validated these with the reported QTLs in our earlier study to find the stable
and consistent QTLs across populations. Also, with Illumina RNA-sequencing we
checked the differential expression of gene (DEG) transcripts between parents and
pools of RILs with high and low nitrogen use efficiency (NUE) and overlaid these
DEGs on to the common validated QTLs to find candidate genes associated with N
stress tolerance in sorghum. RESULTS: An F7 RIL population derived from a cross
between CK60 (N-stress sensitive) and San Chi San (N-stress tolerant) inbred
sorghum lines was used to map QTLs for 11 agronomic traits tested under different
N-levels. Composite interval mapping analysis detected a total of 32 QTLs for 11
agronomic traits. Validation of these QTLs revealed that of the detected, nine
QTLs from this population were consistent with the reported QTLs in earlier study
using CK60/China17 RIL population. The validated QTLs were located on chromosomes
1, 6, 7, 8, and 9. In addition, root transcriptomic profiling detected 55 and 20
differentially expressed gene (DEG) transcripts between parents and pools of RILs
with high and low NUE respectively. Also, overlay of these DEG transcripts on to
the validated QTLs found candidate genes transcripts for NUE and also showed the
expected differential expression. For example, DEG transcripts encoding Lysine
histidine transporter 1 (LHT1) had abundant expression in San Chi San and the
tolerant RIL pool, whereas DEG transcripts encoding seed storage albumin,
transcription factor IIIC (TFIIIC) and dwarfing gene (DW2) encoding multidrug
resistance-associated protein-9 homolog showed abundant expression in CK60
parent, similar to earlier study. CONCLUSIONS: The validated QTLs among different
mapping populations would be the most reliable and stable QTLs across germplasm.
The DEG transcripts found in the validated QTL regions will serve as future
candidate genes for enhancing NUE in sorghum using molecular approaches.
PMID- 28697784
TI - Exome sequencing reveals independent SGCD deletions causing limb girdle muscular
dystrophy in Boston terriers.
AB - BACKGROUND: Limb-girdle muscular dystrophies (LGMDs) are a heterogeneous group of
inherited autosomal myopathies that preferentially affect voluntary muscles of
the shoulders and hips. LGMD has been clinically described in several breeds of
dogs, but the responsible mutations are unknown. The clinical presentation in
dogs is characterized by marked muscle weakness and atrophy in the shoulder and
hips during puppyhood. METHODS: Following clinical evaluation, the identification
of the dystrophic histological phenotype on muscle histology, and demonstration
of the absence of sarcoglycan-sarcospan complex by immunostaining, whole exome
sequencing was performed on five Boston terriers: one affected dog and its three
family members and one unrelated affected dog. RESULTS: Within sarcoglycan-delta
(SGCD), a two base pair deletion segregating with LGMD in the family was
discovered, and a deletion encompassing exons 7 and 8 was found in the unrelated
dog. Both mutations are predicted to cause an absence of SGCD protein, confirmed
by immunohistochemistry. The mutations are private to each family. CONCLUSIONS:
Here, we describe the first cases of canine LGMD characterized at the molecular
level with the classification of LGMD2F.
PMID- 28697785
TI - Effect of aquatic physical therapy on pain perception, functional capacity and
quality of life in older people with knee osteoarthritis: study protocol for a
randomized controlled trial.
AB - BACKGROUND: Aquatic therapy promotes short-term benefits for patients with knee
osteoarthritis (OA), and it may be the first therapeutic option for this
pathological condition. The objective of this study was to investigate the
effects of an aquatic therapy program on pain intensity, functional ability, and
quality of life in older people with knee OA. METHODS/DESIGN: This is a parallel,
two-arm, open, randomized controlled clinical trial with older people with knee
OA. Volunteers will be allocated to an aquatic intervention group (WG), subjected
to the intervention, or to a control group, not be subjected to any kind of
intervention. Data collection pre- and postintervention will be composed of the
evaluation of the perception of pain by visual analogue scale with application of
nociceptive stimuli in four anatomical points of the knee, functional fitness
tests, and application of the World Health Organization Quality of Life Scale
abbreviated version and Western Ontario and McMaster Universities Osteoarthritis
Index. The program will last 12 weeks, consisting of aerobic and functional
exercises in the form of circuit training. DISCUSSION: The objective of this
clinical trial is to evaluate the effect of aquatic therapy in elderly patients
with knee OA. The study is guided by practice-based scientific evidence for the
use of aquatic rehabilitation exercises. It is expected that the WG volunteers
will show reduced pain intensity, increased flexibility, and improved functional
capacity and quality of life. It is believed that the desired results can be
attributed to physical and physiological effects of immersion in warm water
associated with the exercise protocol proposed. The data will be published after
completion of the study. TRIAL REGISTRATION: Brazilian Registry of Clinical
Trials (ReBEC) registration number: RBR-78h48d . Registered on 19 August 2015.
PMID- 28697786
TI - Spinal bone metastases in colorectal cancer: a retrospective analysis of
stability, prognostic factors and survival after palliative radiotherapy.
AB - BACKGROUND: This retrospective analysis aimed to analyse the stability of spinal
bone metastases in colorectal cancer (CRC) patients following radiotherapy (RT)
by use of a validated score and to assess prognostic factors for stability and
survival. METHODS: Ninety-four patients with osteolytic spinal bone metastases
from CRC were treated at the Department of Radiation Oncology at the University
Hospital Heidelberg between 2000 and 2014. The stability of each affected
vertebral body was assessed according to the validated Taneichi bone stability
score on the basis of the treatment planning CT scan prior to RT and also based
on the follow-up CT examinations at 3 and 6 months after RT. Additionally, bone
survival rates (time between first day of RT and death from any cause) as well as
prognostic factors for bone survival were evaluated for all study patients.
RESULTS: Before RT, 59 patients (63%) were rated unstable according to the
Taneichi score. Pathological fractures within the irradiated region were
diagnosed in 43 patients (46%) prior to RT. New fractures or progression of
previously collapsed vertebrae were diagnosed in 4 patients (4%) after
irradiation. Significant re-calcification and stabilization of former unstable
bone metastases was only observed in 3/59 patients (3%) and 5/59 patients (9%).
The median bone survival was 4.2 months (range 0.5-67.3 months) and 6 months
after RT 61% of the patients were dead. Karnofsky performance score (KPS) (< 70%
vs. >= 70%), chemotherapy and bisphosphonate therapy were predictive prognostic
factors for bone survival. CONCLUSIONS: Our study population is characterized by
poor bone survival and low re-calcification rates of unstable spinal bone lesions
3 and 6 months after RT. To avoid unnecessary hospitalisation and improve
remaining QoL, short fractionated treatment schedules of RT may be prefered in
this highly palliative situation, particularly for patients with a KPS < 70%.
PMID- 28697787
TI - A systematic review, and meta-analyses, of the impact of health-related claims on
dietary choices.
AB - BACKGROUND: Health-related claims are statements regarding the nutritional
content of a food (nutrition claims) and/or indicate that a relationship exists
between a food and a health outcome (health claims). Their impact on food
purchasing or consumption decisions is unclear. This systematic review measured
the effect of health-related claims, on pre-packaged foods in retail settings, on
adult purchasing decisions (real and perceived). METHODS: In September 2016, we
searched MEDLINE, EMBASE, PsychINFO, CAB abstracts, Business Source Complete, and
Web of Science/Science Citation Index & Social Science Citation Index for
articles in English published in peer-review journals. Studies were included if
they were controlled experiments where the experimental group(s) included a
health-related claim and the control group involved an identical product without
a health-related claim. Included studies measured (at an individual or population
level); actual or intended choice, purchases, and/or consumption. The primary
outcome was product choices and purchases, the secondary outcome was food
consumption and preference. Results were standardised through calculating odds
ratios and 95% confidence intervals (CI) for the likelihood of choosing a product
when a health-related claim was present. Results were combined in a random
effects meta-analysis. RESULTS: Thirty-one papers were identified, 17 of which
were included for meta-analyses. Most studies were conducted in Europe (n = 17)
and the USA (n = 7). Identified studies were choice experiments that measured the
likelihood of a product being chosen when a claim was present compared to when a
claim was not present, (n = 16), 15 studies were experiments that measured
either; intent-rating scale outcomes (n = 8), consumption (n = 6), a combination
of the two (n = 1), or purchase data (n = 1). Overall, 20 studies found that
claims increase purchasing and/or consumption, eight studies had mixed results,
and two studies found consumption/purchasing reductions. The meta-analyses of 17
studies found that health-related claims increase consumption and/or purchasing
(OR 1.75, CI 1.60-1.91). CONCLUSION: Health-related claims have a substantial
effect on dietary choices. However, this finding is based on research mostly
conducted in artificial settings. Findings from natural experiments have yielded
smaller effects. Further research is needed to assess effects of claims in real
world settings. TRIAL REGISTRATION: PROSPERO systematic review registration
number: CRD42016044042 .
PMID- 28697788
TI - Anatomic, histopathologic, and echocardiographic features in a dog with an
atypical pulmonary valve stenosis with a fibrous band of tissue and a patent
ductus arteriosus.
AB - BACKGROUND: Congenital pulmonary valve stenosis and patent ductus arteriosus are
common congenital heart defects in dogs. However, concurrence of atypical
pulmonary valve stenosis and patent ductus arteriosus is uncommon. This report
describes the anatomic, histopathologic, and echocardiographic features in a dog
with concomitant pulmonary valve stenosis and patent ductus arteriosus with
atypical pulmonary valve dysplasia that included a fibrous band of tissue. CASE
PRESENTATION: A 1.5-year-old intact female Chihuahua dog weighing 3.3 kg
presented with a continuous grade VI cardiac murmur, poor exercise tolerance, and
an intermittent cough. Echocardiography indicated pulmonary valve stenosis, a
thickened dysplastic valve without annular hypoplasia, and a type IIA patent
ductus arteriosus. The pulmonary valve was thick line-shaped in systole and dome
shaped towards the right ventricular outflow tract in diastole. The dog suffered
a fatal cardiac arrest during an attempted balloon pulmonary valvuloplasty.
Necropsy revealed pulmonary valve dysplasia, commissural fusion, and incomplete
opening and closing of the pulmonary valve because of a fibrous band of tissue
causing adhesion between the right ventricular outflow tract and the dysplastic
intermediate cusp of the valve. CONCLUSIONS: A fibrous band of tissue between the
right ventricular outflow track and the pulmonary valve should be considered as a
cause of pulmonary valve stenosis. Pulmonary valve stenosis and patent ductus
arteriosus can have conflicting effects on diastolic and systolic dysfunction,
respectively. Therefore, beta-blockers should always be used carefully,
particularly in patients with a heart defect where there is concern about left
ventricular systolic function.
PMID- 28697789
TI - Improvement in asymmetric dimethylarginine and oxidative stress in patients with
limb salvage after autologous mononuclear stem cell application for critical limb
ischemia.
AB - BACKGROUND: Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric
oxide synthase, acts as an inhibitor of angiogenesis and is associated with an
increased risk of cardiovascular mortality. Administration of stem cells may
affect endogenous mechanisms that regulate ADMA production and metabolism. The
aim of the present study was to analyze ADMA concentration and changes in
oxidative stress in patients with advanced critical limb ischemia (CLI) after
bone marrow-derived mononuclear cell (BM-MNC) therapy. METHODS: Fifty patients
(age 64 +/- 11 years, 44 males, 6 females) with advanced CLI (Rutherford category
5 or 6) not eligible for revascularization were treated by intramuscular (n = 25)
or intra-arterial (n = 25) injection of 40 ml BM-MNC concentrate. Patients with
limb salvage and improved wound healing after 6 months were considered responders
to cell therapy. The concentrations of markers of oxidative stress and
angiogenesis were analyzed before, and at 3 and 6 months after BM-MNC delivery.
RESULTS: At 6-month follow-up, four patients died of reasons unrelated to stem
cell therapy. Among the survivors, 80% (37/46) showed limb salvage and improved
wound healing. At 6 months follow-up, ADMA concentration significantly decreased
in patients with limb salvage (1.74 +/- 0.66 to 0.90 +/- 0.49 MUmol/L, p <
0.001), in parallel with decreased tumor necrosis factor (TNF)-alpha (2.22 +/-
0.16 to 1.94 +/- 0.38 pg/ml, p < 0.001), and increased reduced glutathione (6.96
+/- 3.1 to 8.67 +/- 4.2 MUmol/L, p = 0.02), superoxide dismutase activity (168 +/
50 to 218 +/- 37 U/L, p = 0.002), and coenzyme Q10 concentration (468 +/- 182 to
598 +/- 283 MUg/L, p = 0.02). The number of delivered BM-MNCs significantly
correlated with the decrease in ADMA concentration at 3 months (p = 0.004, r =
0.48) and the decrease in TNF-alpha concentration at 6 months (p = 0.03, r =
0.44) after cell delivery. ADMA or TNF-alpha improvement did not correlate with
the number of applied CD34+ cells, C-reactive protein concentration, leukocyte
count, or the dose of atorvastatin. CONCLUSIONS: The therapeutic benefit of BM
MNC therapy is associated with reduced ADMA levels and oxidative stress.
Regulation of the ADMA-nitric oxide axis and improved antioxidant status may be
involved in the beneficial effects of stem cell therapy. TRIAL REGISTRATION: The
study was approved and retrospectively registered by ISRCTN registry,
ISRCTN16096154 . Registered on 26 July 2016.
PMID- 28697790
TI - Fully automated segmentation of callus by micro-CT compared to biomechanics.
AB - BACKGROUND: A high percentage of closed femur fractures have slight comminution.
Using micro-CT (MUCT), multiple fragment segmentation is much more difficult than
segmentation of unfractured or osteotomied bone. Manual or semi-automated
segmentation has been performed to date. However, such segmentation is extremely
laborious, time-consuming and error-prone. Our aim was to therefore apply a fully
automated segmentation algorithm to determine MUCT parameters and examine their
association with biomechanics. METHODS: The femura of 64 rats taken after
randomised inhibitory or neutral medication, in terms of the effect on fracture
healing, and controls were closed fractured after a Kirschner wire was inserted.
After 21 days, MUCT and biomechanical parameters were determined by a fully
automated method and correlated (Pearson's correlation). RESULTS: The fully
automated segmentation algorithm automatically detected bone and simultaneously
separated cortical bone from callus without requiring ROI selection for each
single bony structure. We found an association of structural callus parameters
obtained by MUCT to the biomechanical properties. However, results were only
explicable by additionally considering the callus location. CONCLUSIONS: A large
number of slightly comminuted fractures in combination with therapies that
influence the callus qualitatively and/or quantitatively considerably affects the
association between MUCT and biomechanics. In the future, contrast-enhanced MUCT
imaging of the callus cartilage might provide more information to improve the non
destructive and non-invasive prediction of callus mechanical properties. As
studies evaluating such important drugs increase, fully automated segmentation
appears to be clinically important.
PMID- 28697791
TI - Blood transfusion in elderly patients with chronic anemia: a qualitative analysis
of the general practitioners' attitudes.
AB - BACKGROUND: Blood transfusion in chronic anemia is not covered by guidelines
specific to older adults. When they consider that this treatment is necessary in
elderly patients, French general practitioners (GPs) contact a hospital
specialist to plan a transfusion. METHODS: Twenty French GPs were questioned
individually regarding their approach to blood transfusion using semi-structured
interviews. Each interview was recorded, typed up verbatim and then coded using
an inductive procedure by theme, in a cross-over design (two researchers) in two
phases: analysis and summary, followed by grouping of the recorded comments.
RESULTS: The criteria for transfusion were hemoglobin level < 8 g/dL and cardiac
comorbidities. Some geriatric issues, such as cognitive disorder or dependence,
were considered, either as aspects of frailty favoring transfusion or as markers
of reduced life expectancy that limit care. Falls and fear of an unpleasant death
from anemia prompted GPs to order blood transfusion. The patient's family
provided guidance, but the patient was not routinely consulted. The specialists
were rarely asked to participate in decision making. GPs' perceptions were
ambivalent: they considered transfusion to be extraordinary and magical, but also
pointless since its effects are transient. CONCLUSION: The decision to give a
transfusion to an elderly patient with chronic anemia is deemed complex, but GPs
seem to take it alone, sometimes guided by the patient's family. The drawing up
of an advance care plan could help involve the patient in decision making.
PMID- 28697792
TI - Rupture of posterior cruciate ligament leads to radial displacement of the medial
meniscus.
AB - BACKGROUND: To explore the association between the rupture of posterior cruciate
ligament (PCL) and the radial displacement of medial meniscus under the
conditions of different flexion and various axial loads. METHODS: The radial
displacement value of medial meniscus was measured for the specimens of normal
adult knee joints, including 12 intact PCLs, 6 ruptures of the anterolateral
bundle (ALB), 6 ruptures of the postmedial bundle (PMB), and 12 complete
ruptures. The measurement was conducted at 0 degrees , 30 degrees , 60 degrees ,
and 90 degrees of knee flexion angles under 200 N, 400 N, 600 N, 800 N and 1000
N of axial loads respectively. RESULTS: The displacement values of medial
meniscus of the ALB rupture group increased at 0 degrees flexion under 800 N and
1000 N, and at 30 degrees , 60 degrees and 90 degrees flexion under all loads
in comparison with the PCL intact group. The displacement values of the PMB
rupture group was higher at 0 degrees and 90 degrees flexion under all loads,
and at 30 degrees and 60 degrees flexion under 800 N and 1000 N loads. The
displacement of the PCL complete rupture group increased at all flexion angles
under all loads. CONCLUSIONS: Either partial or complete rupture of the PCL can
increase in the radial displacement of the medial meniscus, which may explain the
degenerative changes that occuring in the medial meniscus due to PCL injury.
Therefore, early reestablishment of the PCL is necessarily required in order to
maintain stability of the knee joint after PCL injury.
PMID- 28697793
TI - Collagen triple helix repeat containing-1 negatively regulated by microRNA-30c
promotes cell proliferation and metastasis and indicates poor prognosis in breast
cancer.
AB - BACKGROUND: Collagen triple helix repeat containing-1 (CTHRC1), which was firstly
identified overexpressed in the adventitia and neointima of injured rat arteries,
could inhibit collagen expression and increase cell migration. It was then found
to be ubiquitously expressed in numerous cell types such as fibroblasts and
smooth muscle cells, and aberrantly up-regulated in several malignant tumors.
However, the functional role of CTHRC1 and its related mechanism in breast cancer
still remains unclear. METHODS: CTHRC1 expressions in breast cancer tissues and
cells were assessed by qRT-PCR, western blot and immunohistochemistry. The
relative expression level of miR-134, miR-155, miR-30c and miR-630 in breast
cancer cells respectively was detected by qRT-PCR. Wild type (Wt) and Mutant type
(Mut) CTHRC1 3'UTR sequences were cloned into a psi-CHECK2 reporter vector, and
the relative luciferase activity was detected by dual-luciferase reporter assay
in indicated cells. The effect of ectopic expression of miR-30c or gain and loss
of CTHRC1 on cell viability, cell proliferation, cell cycle progression and
apoptosis, cell invasion and migration was respectively detected by CCK-8 assay,
colony formation assay, flow cytometry analysis, transwell invasion/migration
assay. Protein levels of beta-catenin, active beta-catenin, normal and
phosphorylated form of GSK-3beta were detected by western blot in indicated
cells. Immunofluorescence staining of beta-catenin was performed to observe
nuclear localization. RESULTS: We found CTHRC1 was frequently up-regulated in
human breast cancer cells and tissues. Then our cohort study and further meta
analysis validated high expression of CTHRC1 was associated with aggressive
clinicopathological features and poor clinical outcome of breast cancer patients.
In addition, CTHRC1 promoted cell proliferation, invasion and migration and
suppressed cell apoptosis in breast cancer, which might be by activating GSK
3beta/beta-catenin signaling and inhibiting Bax/Caspase-9/Caspase-3 signaling
respectively; and these biological functions of CTHRC1 could be directly
negatively regulated by miR-30c. CONCLUSION: Taken together, we identified the
role of miR-30c/CTHRC1 axis in breast cancer progression and demonstrated CTHRC1
may serve as a prognostic biomarker and therapeutic target for breast cancer.
PMID- 28697794
TI - Factors associated with maternal mortality in Malawi: application of the three
delays model.
AB - BACKGROUND: The three delays model proposes that maternal mortality is associated
with delays in: 1) deciding to seek care; 2) reaching the healthcare facility;
and 3) receiving care. Previously, the majority of women who died were reported
to have experienced type 1 and 2 delays. With increased coverage of healthcare
services, we sought to explore the relative contribution of each type of delay.
METHOD: 151 maternal deaths were identified during a 12-month reproductive age
mortality survey (RAMOS) conducted in Malawi; verbal autopsy and facility-based
medical record reviews were conducted to obtain details about the circumstances
surrounding each death. Using the three delays framework, data were analysed for
women who had; 1) died at a healthcare facility, 2) died at home but had
previously accessed care and 3) died at home and had not accessed care. RESULTS:
62.2% (94/151) of maternal deaths occurred in a healthcare facility and a further
21.2% (32/151) of mothers died at home after they had accessed care at a
healthcare facility. More than half of all women who died at a healthcare
facility (52.1%) had experienced more than one type of delay. Type 3 delays were
the most significant delay for women who died at a healthcare facility or women
who died at home after they had accessed care, and was identified in 96.8% of
cases. Type 2 delays were experienced by 59.6% and type 1 delays by 39.7% of all
women. Long waiting hours before receiving treatment at a healthcare facility,
multiple delays at the time of admission, shortage of drugs, non-availability and
incompetence of skilled staff were some of the major causes of type 3 delays.
Distance to a healthcare facility was the main problem resulting in type 2
delays. CONCLUSION: The majority of women do try to reach health services when an
emergency occurs, but type 3 delays present a major problem. Improving quality of
care at healthcare facility level will help reduce maternal mortality.
PMID- 28697795
TI - Improved prosthetic hand control with concurrent use of myoelectric and inertial
measurements.
AB - BACKGROUND: Myoelectric pattern recognition systems can decode movement intention
to drive upper-limb prostheses. Despite recent advances in academic research, the
commercial adoption of such systems remains low. This limitation is mainly due to
the lack of classification robustness and a simultaneous requirement for a large
number of electromyogram (EMG) electrodes. We propose to address these two issues
by using a multi-modal approach which combines surface electromyography (sEMG)
with inertial measurements (IMs) and an appropriate training data collection
paradigm. We demonstrate that this can significantly improve classification
performance as compared to conventional techniques exclusively based on sEMG
signals. METHODS: We collected and analyzed a large dataset comprising recordings
with 20 able-bodied and two amputee participants executing 40 movements.
Additionally, we conducted a novel real-time prosthetic hand control experiment
with 11 able-bodied subjects and an amputee by using a state-of-the-art
commercial prosthetic hand. A systematic performance comparison was carried out
to investigate the potential benefit of incorporating IMs in prosthetic hand
control. RESULTS: The inclusion of IM data improved performance significantly, by
increasing classification accuracy (CA) in the offline analysis and improving
completion rates (CRs) in the real-time experiment. Our findings were consistent
across able-bodied and amputee subjects. Integrating the sEMG electrodes and IM
sensors within a single sensor package enabled us to achieve high-level
performance by using on average 4-6 sensors. CONCLUSIONS: The results from our
experiments suggest that IMs can form an excellent complimentary source signal
for upper-limb myoelectric prostheses. We trust that multi-modal control
solutions have the potential of improving the usability of upper-extremity
prostheses in real-life applications.
PMID- 28697796
TI - Patients' preferences for primary health care - a systematic literature review of
discrete choice experiments.
AB - BACKGROUND: Primary care is a key element of health care systems and addresses
the main health problems of the population. Due to the demographic change,
primary care even gains in importance. The knowledge of the patients' preferences
can help policy makers as well as physicians to set priorities in their effort to
make health care delivery more responsive to patients' needs. Our objective was
to describe which aspects of primary care were included in preference studies and
which of them were the most preferred aspects. METHODS: In order to elicit the
preferences for primary care, a systematic literature search was conducted. Two
researchers searched three electronic databases (PubMed, Scopus, and PsycINFO)
and conducted a narrative synthesis. Inclusion criteria were: focus on primary
health care delivery, discrete choice experiment as elicitation method, and
studies published between 2006 and 2015 in English language. RESULTS: We
identified 18 studies that elicited either the patients' or the population's
preferences for primary care based on a discrete choice experiment. Altogether
the studies used 16 structure attributes, ten process attributes and four outcome
attributes. The most commonly applied structure attribute was "Waiting time till
appointment", the most frequently used process attribute was "Shared decision
making / professional's attention paid to your views". "Receiving the 'best'
treatment" was the most commonly applied outcome attribute. Process attributes
were most often the ones of highest importance for patients or the population.
The attributes and attribute levels used in the discrete choice experiments were
identified by literature research, qualitative research, expert interviews, or
the analysis of policy documents. CONCLUSIONS: The results of the DCE studies
show different preferences for primary health care. The diversity of the results
may have several reasons, such as the method of analysis, the selection procedure
of the attributes and their levels or the specific research question of the
study. As the results of discrete choice experiments depend on many different
factors, it is important for a better comprehensibility of the studies to
transparently report the steps undertaken in a study as well as the interim
results regarding the identification of attributes and levels.
PMID- 28697797
TI - Increasing students' physical activity during school physical education:
rationale and protocol for the SELF-FIT cluster randomized controlled trial.
AB - BACKGROUND: The Self-determined Exercise and Learning For FITness (SELF-FIT) is a
multi-component school-based intervention based on tenets of self-determination
theory. SELF-FIT aims to increase students' moderate-to-vigorous physical
activity (MVPA) during physical education lessons, and enhance their autonomous
motivation towards fitness activities. Using a cluster randomized controlled
trial, we aim to examine the effects of the intervention on students' MVPA during
school physical education. METHODS: Secondary 2 students (approximately aged 14
years) from 26 classes in 26 different schools will be recruited. After baseline
assessments, students will be randomized into either the experimental group or
wait-list control group using a matched-pair randomization. Teachers allocated to
the experimental group will attend two half-day workshops and deliver the SELF
FIT intervention for 8 weeks. The main intervention components include training
teachers to teach in more need supportive ways, and conducting fitness exercises
using a fitness dice with interchangeable faces. Other motivational components,
such as playing music during classes, are also included. The primary outcome of
the trial is students' MVPA during PE lessons. Secondary outcomes include
students' leisure-time MVPA, perceived need support from teachers, need
satisfaction, autonomous motivation towards physical education, intention to
engage in physical activity, psychological well-being, and health-related fitness
(cardiorespiratory and muscular fitness). Quantitative data will be analyzed
using multilevel modeling approaches. Focus group interviews will also be
conducted to assess students' perceptions of the intervention. DISCUSSION: The
SELF-FIT intervention has been designed to improve students' health and well
being by using high-intensity activities in classes delivered by teachers who
have been trained to be autonomy needs supportive. If successful, scalable
interventions based on SELF-FIT could be applied in physical education at large.
TRIAL REGISTRATION: The trial is registered at the Australia New Zealand Clinical
Trial Registry (Trial ID: ACTRN12615000633583 ; date of registration: 18 June
2015).
PMID- 28697798
TI - A proteomic analysis of LRRK2 binding partners reveals interactions with multiple
signaling components of the WNT/PCP pathway.
AB - BACKGROUND: Autosomal-dominant mutations in the Park8 gene encoding Leucine-rich
repeat kinase 2 (LRRK2) have been identified to cause up to 40% of the genetic
forms of Parkinson's disease. However, the function and molecular pathways
regulated by LRRK2 are largely unknown. It has been shown that LRRK2 serves as a
scaffold during activation of WNT/beta-catenin signaling via its interaction with
the beta-catenin destruction complex, DVL1-3 and LRP6. In this study, we examine
whether LRRK2 also interacts with signaling components of the WNT/Planar Cell
Polarity (WNT/PCP) pathway, which controls the maturation of substantia nigra
dopaminergic neurons, the main cell type lost in Parkinson's disease patients.
METHODS: Co-immunoprecipitation and tandem mass spectrometry was performed in a
mouse substantia nigra cell line (SN4741) and human HEK293T cell line in order to
identify novel LRRK2 binding partners. Inhibition of the WNT/beta-catenin
reporter, TOPFlash, was used as a read-out of WNT/PCP pathway activation. The
capacity of LRRK2 to regulate WNT/PCP signaling in vivo was tested in Xenopus
laevis' early development. RESULTS: Our proteomic analysis identified that LRRK2
interacts with proteins involved in WNT/PCP signaling such as the PDZ domain
containing protein GIPC1 and Integrin-linked kinase (ILK) in dopaminergic cells
in vitro and in the mouse ventral midbrain in vivo. Moreover, co
immunoprecipitation analysis revealed that LRRK2 binds to two core components of
the WNT/PCP signaling pathway, PRICKLE1 and CELSR1, as well as to FLOTILLIN-2 and
CULLIN-3, which regulate WNT secretion and inhibit WNT/beta-catenin signaling,
respectively. We also found that PRICKLE1 and LRRK2 localize in signalosomes and
act as dual regulators of WNT/PCP and beta-catenin signaling. Accordingly,
analysis of the function of LRRK2 in vivo, in X. laevis revelaed that LRKK2 not
only inhibits WNT/beta-catenin pathway, but induces a classical WNT/PCP phenotype
in vivo. CONCLUSIONS: Our study shows for the first time that LRRK2 activates the
WNT/PCP signaling pathway through its interaction to multiple WNT/PCP components.
We suggest that LRRK2 regulates the balance between WNT/beta-catenin and WNT/PCP
signaling, depending on the binding partners. Since this balance is crucial for
homeostasis of midbrain dopaminergic neurons, we hypothesize that its alteration
may contribute to the pathophysiology of Parkinson's disease.
PMID- 28697799
TI - Symmetric and asymmetric dimethylarginine as risk markers of cardiovascular
disease, all-cause mortality and deterioration in kidney function in persons with
type 2 diabetes and microalbuminuria.
AB - BACKGROUND: To evaluate symmetric dimethylarginine (SDMA) and asymmetric
dimethylarginine (ADMA) as risk markers of cardiovascular disease, all-cause
mortality and deterioration in renal function in a well characterised type 2
diabetic population with microalbuminuria and without symptoms of coronary artery
disease. METHODS: 200 participants followed for 6.1 years. SDMA and ADMA were
measured at baseline. Endpoints included (1) composite cardiovascular endpoint (n
= 40); (2) all-cause mortality (n = 26); and (3) decline in eGFR of >30% (n =
42). Cox models were unadjusted and adjusted for traditional risk factors (sex,
age, systolic blood pressure, LDL-cholesterol, smoking, HbA1c, creatinine and
urinary albumin excretion rate). To assess if SDMA or ADMA improved risk
prediction beyond traditional risk factors we calculated c statistics and
relative integrated discrimination improvement (rIDI). C statistic (area under
the curve) quantifies the model's improved ability to discriminate events from
non-events. rIDI quantifies the increase in separation of events and non-events
on a relative scale. RESULTS: Higher SDMA was associated with increased risk of
all three endpoints (unadjusted: p <= 0.001; adjusted: p <= 0.02). Higher ADMA
was associated with all-cause mortality (unadjusted: p = 0.002; adjusted: p =
0.006), but not cardiovascular disease or decline in eGFR (p >= 0.29).The c
statistic was not significant for any of the endpoints for either SDMA or ADMA (p
>= 0.10). The rIDI for SDMA was 15.0% (p = 0.081) for the cardiovascular
endpoint, 52.5% (p = 0.025) for all-cause mortality and 48.8% (p = 0.007) for
decline in eGFR; for ADMA the rIDI was 49.1% (p = 0.017) for all-cause mortality.
CONCLUSION: In persons with type 2 diabetes and microalbuminuria higher SDMA was
associated with incident cardiovascular disease, all-cause mortality and
deterioration in renal function. Higher ADMA was associated with all-cause
mortality. SDMA and ADMA significantly improved risk prediction for all-cause
mortality, and SDMA for deterioration in renal function beyond traditional risk
factors.
PMID- 28697800
TI - SegCorr a statistical procedure for the detection of genomic regions of
correlated expression.
AB - BACKGROUND: Detecting local correlations in expression between neighboring genes
along the genome has proved to be an effective strategy to identify possible
causes of transcriptional deregulation in cancer. It has been successfully used
to illustrate the role of mechanisms such as copy number variation (CNV) or
epigenetic alterations as factors that may significantly alter expression in
large chromosomal regions (gene silencing or gene activation). RESULTS: The
identification of correlated regions requires segmenting the gene expression
correlation matrix into regions of homogeneously correlated genes and assessing
whether the observed local correlation is significantly higher than the
background chromosomal correlation. A unified statistical framework is proposed
to achieve these two tasks, where optimal segmentation is efficiently performed
using dynamic programming algorithm, and detection of highly correlated regions
is then achieved using an exact test procedure. We also propose a simple and
efficient procedure to correct the expression signal for mechanisms already known
to impact expression correlation. The performance and robustness of the proposed
procedure, called SegCorr, are evaluated on simulated data. The procedure is
illustrated on cancer data, where the signal is corrected for correlations caused
by copy number variation. It permitted the detection of regions with high
correlations linked to epigenetic marks like DNA methylation. CONCLUSIONS:
SegCorr is a novel method that performs correlation matrix segmentation and
applies a test procedure in order to detect highly correlated regions in gene
expression.
PMID- 28697801
TI - Interferon-gamma-dependent control of Anaplasma phagocytophilum by murine
neutrophil granulocytes.
AB - BACKGROUND: Anaplasma phagocytophilum is a Gram-negative obligate intracellular
bacterium that is transmitted by ticks of the Ixodes ricinus complex. It
replicates in neutrophils and elicits febrile disease in humans and animals.
Because of its striking tropism for neutrophils, A. phagocytophilum has been used
as a model organism to study the immune response against obligate intracellular
pathogens. In mice, the control of A. phagocytophilum in the early phase of
infection is dependent on natural killer cell-derived interferon-gamma (IFN
gamma). In contrast, the final elimination strictly requires CD4+ T-cells. It is
a matter of debate, whether neutrophils serve only as host cells or as killer
cells as well. RESULTS: To study this, we used in vitro generated murine
neutrophils with defects in major antimicrobial molecules such as NADPH-oxidase
(gp91phox-/-), myeloperoxidase (MPO-/-) and inducible nitric oxide synthase (iNOS
/-). However, bacterial growth in gene-deficient neutrophils was comparable to
that in wild-type cells. Whereas gp91phox and MPO expression remained unchanged,
the infection led to an induction of iNOS. In neutrophils stimulated with IFN
gamma, bacterial growth was significantly impaired, and iNOS was induced.
However, the antibacterial effect of IFN-gamma was still seen in iNOS-/-
neutrophils. CONCLUSION: Thus, murine in vitro generated neutrophils stimulated
with IFN-gamma seem to act as killer cells by an iNOS-independent mechanism.
PMID- 28697802
TI - Outcomes of subsyndromal delirium in ICU: a systematic review and meta-analysis.
AB - BACKGROUND: Subsyndromal delirium (SSD) is a frequent condition and has been
commonly described as an intermediate stage between delirium and normal
cognition. However, the true frequency of SSD and its impact on clinically
relevant outcomes in the intensive care unit (ICU) remains unclear. METHODS: We
performed a systematic search in PubMed, Embase, CINAHL, Cochrane Library, and
PsychINFO, with no language restrictions, up to 1 October 2016 to identify
publications that evaluated SSD in ICU patients. RESULTS: The six eligible
studies were evaluated. SSD was present in 950 (36%) patients. Four studies
evaluated only surgical patients. Four studies used the Intensive Care Delirium
Screening Checklist (ICDSC) and two used the Confusion Assessment Method (CAM)
score to diagnose SSD. The meta-analysis showed an increased hospital length of
stay (LOS) in SSD patients (0.31, 0.12-0.51, p = 0.002; I 2 = 34%). Hospital
mortality was described in two studies but it was not significant (hazard ratio
0.97, 0.61-1.55, p = 0.90 and 5% vs 9%, p = 0.05). The use of antipsychotics in
SSD patients to prevent delirium was evaluated in two studies but it did not
modify ICU LOS (6.5 (4-8) vs 7 (4-9) days, p = 0.66 and 2 (2-3) vs 3 (2-3) days,
p = 0.517) or mortality (9 (26.5%) vs 7 (20.6%), p = 0.55). CONCLUSIONS: SSD
occurs in one-third of the ICU patients and has limited impact on the outcomes.
The current literature concerning SSD is composed of small-sample studies with
methodological differences, impairing a clear conclusion about the association
between SSD and progression to delirium or worse ICU clinical outcomes.
PMID- 28697803
TI - Effects of a physical activity and nutrition program in retirement villages: a
cluster randomised controlled trial.
AB - BACKGROUND: This cluster randomised controlled trial aimed to determine if a 6-
month home-based intervention could improve the physical activity and dietary
behaviours of adults aged 60 to 80 years living in retirement villages located in
Perth, Western Australia. METHODS: Participants (n = 363) from 38 retirement
villages were recruited into the trial and allocated to the intervention (n =
197: 17 sites) or control (n = 166: 21 sites) group and were blinded. Previously
validated instruments-Fat and Fibre Barometer and International Physical Activity
Questionnaire, along with anthropometric measures (weight, height, waist and hip
circumferences) and blood pressure were collected at baseline and 6 -month time
period. Comparisons between intervention and control groups were undertaken pre-
and post- intervention using univariate chi-square and t-tests. Multi-level mixed
regression analyses were then conducted to ascertain the effects of the
intervention on changes in the outcome variables over time and between groups.
RESULTS: A total of 139 (70.5%) intervention and 141 (84.9%) control group
participants completed the program and post-test assessments. The intervention
group demonstrated significant increases in time (80 min more per week on
average) devoted to moderate-intensity physical activity, engagement in strength
exercises (from 23.7% to 48.2%), frequency of fruit consumed as well as fat
avoidance and fibre intake scores, in addition to a 0.5 kg mean reduction in
weight post program, whereas no apparent changes were observed in the control
group. Mixed regression results further confirmed statistically significant
improvements in weight loss (p < 0.05), engagement in strength exercises (p <
0.001) and fruit intake (p = 0.012) by the intervention participants at post-test
relative to their controls. CONCLUSIONS: Retirement offers a time to reassess
lifestyle, and adopt positive health enhancing physical activity and dietary
behaviours. This intervention was successful in improving weight, engagement in
strength exercises, increasing levels of moderate-intensity physical activity and
consumption of fruit among retirement village residents. Further investigation is
needed on how to better engage retirement village managers in such programs.
TRIAL REGISTRATION: Australia and New Zealand Clinical Trial Registry
(ACTRN12612001168842) registered November 2, 2012.
PMID- 28697805
TI - The influence of prior laparoscopic experience on learning laparoendoscopic
single site surgery: a prospective comparative preliminary study using
cystorraphy in a live porcine model.
AB - BACKGROUND: The purpose of this study is to assess the impact of prior
laparoscopic experience on the ability to learn laparoendoscopic single site
surgery (LESS) skills. METHODS: A total of 33 urologists who completed a training
program in LESS surgery were recruited for this study. After completing the
educational course and training, the study participants demonstrated LESS
suturing and knot-tying via a 2-cm cystotomy in a live porcine model for 15 min.
An objective structured assessment of technical skills (OSATS) was used to
evaluate videos of each participant's procedure. The participants were divided
according to laparoscopic experience; advanced experienced group (AS),
intermediate experienced group (IS), novice group (NS). RESULTS: Three
participants in the NS group completed the porcine cystorrhaphy in 15 min
(30.0%), 3 (25.0%) completed the task in the IS group, and 3 (27.2%) completed it
in the AS group. There were no statistically significant differences in the mean
total OSATS quality score (NS; 16.7, IS; 18.5, AS; 16.8) among the 3 groups.
Concerning all each assessment, there were also no statistically significant
difference. Additionaly, the mean total OSATS quantity score (NS; 4.1, IS; 3.5,
AS; 4.3) did not differ significantly among groups. The NS group succeeded a mean
of 1.4 knots, the IS group succeeded 0.9, and the AS group 1.3 (p = 0.727).
CONCLUSIONS: There was no significant difference among the groups in LESS
proficiency after training. Surgeons who were novices in conventional
laparoscopic surgery reached comparable scores to those of experienced
laparoscopic surgeons after training.
PMID- 28697804
TI - Ang II-AT2R increases mesenchymal stem cell migration by signaling through the
FAK and RhoA/Cdc42 pathways in vitro.
AB - BACKGROUND: Mesenchymal stem cells (MSCs) migrate via the bloodstream to sites of
injury and are possibly attracted by inflammatory factors. As a proinflammatory
mediator, angiotensin II (Ang II) reportedly enhances the migration of various
cell types by signaling via the Ang II receptor in vitro. However, few studies
have focused on the effects of Ang II on MSC migration and the underlying
mechanisms. METHODS: Human bone marrow MSCs migration was measured using wound
healing and Boyden chamber migration assays after treatments with different
concentrations of Ang II, an AT1R antagonist (Losartan), and/or an AT2R
antagonist (PD-123319). To exclude the effect of proliferation on MSC migration,
we measured MSC proliferation after stimulation with the same concentration of
Ang II. Additionally, we employed the focal adhesion kinase (FAK) inhibitor PF
573228, RhoA inhibitor C3 transferase, Rac1 inhibitor NSC23766, or Cdc42
inhibitor ML141 to investigate the role of cell adhesion proteins and the Rho
GTPase protein family (RhoA, Rac1, and Cdc42) in Ang II-mediated MSC migration.
Cell adhesion proteins (FAK, Talin, and Vinculin) were detected by western blot
analysis. The Rho-GTPase family protein activities were assessed by G-LISA and F
actin levels, which reflect actin cytoskeletal organization, were detected by
using immunofluorescence. RESULTS: Human bone marrow MSCs constitutively
expressed AT1R and AT2R. Additionally, Ang II increased MSC migration in an AT2R
dependent manner. Notably, Ang II-enhanced migration was not mediated by Ang II
mediated cell proliferation. Interestingly, Ang II-enhanced migration was
mediated by FAK activation, which was critical for the formation of focal
contacts, as evidenced by increased Talin and Vinculin expression. Moreover, RhoA
and Cdc42 were activated by FAK to increase cytoskeletal organization, thus
promoting cell contraction. Furthermore, FAK, Talin, and Vinculin activation and
F-actin reorganization in response to Ang II were prevented by PD-123319 but not
Losartan, indicating that FAK activation and F-actin reorganization were
downstream of AT2R. CONCLUSIONS: These data indicate that Ang II-AT2R regulates
human bone marrow MSC migration by signaling through the FAK and RhoA/Cdc42
pathways. This study provides insights into the mechanisms by which MSCs home to
injury sites and will enable the rational design of targeted therapies to improve
MSC engraftment.
PMID- 28697806
TI - Control of lupus nephritis by changes of gut microbiota.
AB - BACKGROUND: Systemic lupus erythematosus, characterized by persistent
inflammation, is a complex autoimmune disorder with no known cure.
Immunosuppressants used in treatment put patients at a higher risk of infections.
New knowledge of disease modulators, such as symbiotic bacteria, can enable fine
tuning of parts of the immune system, rather than suppressing it altogether.
RESULTS: Dysbiosis of gut microbiota promotes autoimmune disorders that damage
extraintestinal organs. Here we report a role of gut microbiota in the
pathogenesis of renal dysfunction in lupus. Using a classical model of lupus
nephritis, MRL/lpr, we found a marked depletion of Lactobacillales in the gut
microbiota. Increasing Lactobacillales in the gut improved renal function of
these mice and prolonged their survival. We used a mixture of 5 Lactobacillus
strains (Lactobacillus oris, Lactobacillus rhamnosus, Lactobacillus reuteri,
Lactobacillus johnsonii, and Lactobacillus gasseri), but L. reuteri and an
uncultured Lactobacillus sp. accounted for most of the observed effects. Further
studies revealed that MRL/lpr mice possessed a "leaky" gut, which was reversed by
increased Lactobacillus colonization. Lactobacillus treatment contributed to an
anti-inflammatory environment by decreasing IL-6 and increasing IL-10 production
in the gut. In the circulation, Lactobacillus treatment increased IL-10 and
decreased IgG2a that is considered to be a major immune deposit in the kidney of
MRL/lpr mice. Inside the kidney, Lactobacillus treatment also skewed the Treg
Th17 balance towards a Treg phenotype. These beneficial effects were present in
female and castrated male mice, but not in intact males, suggesting that the gut
microbiota controls lupus nephritis in a sex hormone-dependent manner.
CONCLUSIONS: This work demonstrates essential mechanisms on how changes of the
gut microbiota regulate lupus-associated immune responses in mice. Future studies
are warranted to determine if these results can be replicated in human subjects.
PMID- 28697807
TI - Inferring clonal structure in HTLV-1-infected individuals: towards bridging the
gap between analysis and visualization.
AB - BACKGROUND: Human T cell leukemia virus type 1 (HTLV-1) causes adult T cell
leukemia (ATL) in a proportion of infected individuals after a long latency
period. Development of ATL is a multistep clonal process that can be investigated
by monitoring the clonal expansion of HTLV-1-infected cells by isolation of
provirus integration sites. The clonal composition (size, number, and
combinations of clones) during the latency period in a given infected individual
has not been clearly elucidated. METHODS: We used high-throughput sequencing
technology coupled with a tag system for isolating integration sites and
measuring clone sizes from 60 clinical samples. We assessed the role of clonality
and clone size dynamics in ATL onset by modeling data from high-throughput
monitoring of HTLV-1 integration sites using single- and multiple-time-point
samples. RESULTS: From four size categories analyzed, we found that big clones
(B; 513-2048 infected cells) and very big clones (VB; >2048 infected cells) had
prognostic value. No sample harbored two or more VB clones or three or more B
clones. We examined the role of clone size, clone combination, and the number of
integration sites in the prognosis of infected individuals. We found a moderate
reverse correlation between the total number of clones and the size of the
largest clone. We devised a data-driven model that allows intuitive
representation of clonal composition. CONCLUSIONS: This integration site-based
clonality tree model represents the complexity of clonality and provides a global
view of clonality data that facilitates the analysis, interpretation,
understanding, and visualization of the behavior of clones on inter- and intra
individual scales. It is fully data-driven, intuitively depicts the clonality
patterns of HTLV-1-infected individuals and can assist in early risk assessment
of ATL onset by reflecting the prognosis of infected individuals. This model
should assist in assimilating information on clonal composition and understanding
clonal expansion in HTLV-1-infected individuals.
PMID- 28697808
TI - Pyrazinamide resistance-conferring mutations in pncA and the transmission of
multidrug resistant TB in Georgia.
AB - BACKGROUND: The ongoing epidemic of multidrug-resistant tuberculosis (MDR-TB) in
Georgia highlights the need for more effective control strategies. A new regimen
to treat MDR-TB that includes pyrazinamide (PZA) is currently being evaluated and
PZA resistance status will largely influence the success of current and future
treatment strategies. PZA susceptibility testing was not routinely performed at
the National Reference Laboratory (NRL) in Tbilisi between 2010 and September
2015. We here provide a first insight into the prevalence of PZA resistant TB in
this region. METHODS: Phenotypic susceptibility to PZA was determined in a
convenience collection of well-characterised TB patient isolates collected at the
NRL in Tbilisi between 2012 and 2013. In addition, the pncA gene was sequenced
and whole genome sequencing was performed on two isolates. RESULTS: Out of 57
isolates tested 33 (57.9%) showed phenotypic drug resistance to PZA and had a
single pncA mutation. All of these 33 isolates were MDR-TB strains. pncA
mutations were absent in all but one of the 24 PZA susceptible isolate. In total
we found 18 polymorphisms in the pncA gene. From the two major MDR-TB clusters
represented (94-32 and 100-32), 10 of 15, 67.0% and 13 of 14, 93.0% strains,
respectively were PZA resistant. We also identified a member of the potentially
highly transmissive clade A strain carrying the characteristic I6L substitution
in PncA. Another strain with the same MLVA type as the clade A strain acquired a
different mutation in pncA and was genetically more distantly related suggesting
that different branches of this particular lineage have been introduced into this
region. CONCLUSION: In this high MDR-TB setting more than half of the tested MDR
TB isolates were resistant to PZA. As PZA is part of current and planned MDR-TB
treatment regimens this is alarming and deserves the attention of health
authorities. Based on our typing and sequence analysis results we conclude that
PZA resistance is the result of primary transmission as well as acquisition
within the patient and recommend prospective genotyping and PZA resistance
testing in high MDR-TB settings. This is of utmost importance in order to
preserve bacterial susceptibility to PZA to help protect (new) second line drugs
in PZA containing regimens.
PMID- 28697809
TI - Comparison of HCV viral load and its genotype distributions in HCV mono- and
HIV/HCV co-infected illicit drug users.
AB - BACKGROUND: Because of shared modes of transmission, patients with hepatitis C
virus (HCV) infection are often co-infected with other types of hepatitis viruses
and/or HIV. We studied HCV viral load and its genotype patterns among HCV mono-
and HCV/HIV co-infected Illicit Drug Users in Fars province-Iran. METHODS:
Totally, 580 HCV seropositive IDUs referred to Prof. Alborzi Clinical
Microbiology Research Center, Shiraz, Iran, without receiving any anti-HCV
treatment, were enrolled. After their HCV infections were reconfirmed by one step
rapid diagnostic test, HCV RNA level and HCV genotypes were determined by Taq-man
real-time PCR assays. Their HIV serostatus was determined and seropositive
patients were excluded from the group. In addition, 104 HIV/HCV co-infected IDUs
referred from Shiraz Behavioral Diseases Consultation Center (SBDC) were assessed
for HCV RNA level and HCV genotype patterns, as well. RESULTS: The overall
estimated HIV prevalence was 6.7% (39/580) among HCV seropositive IDUs. Genotype
1, the most prevalent genotype in both groups, was detected in 69% and 49% of co-
and mono-infected IDUs, respectively. Median HCV viral load was significantly
higher in HIV/HCV co-infected patients, compared with that among HCV mono
infected counterparts. CONCLUSIONS: Given the higher baseline HCV viral load and
GT1 attributed to poorer treatments response, HCV treatment must be more
considered among HCV/HIV co-infected IDUs, compared to those mono-infected with
HCV.
PMID- 28697810
TI - Healthcare system responses to intimate partner violence in low and middle-income
countries: evidence is growing and the challenges become clearer.
AB - The damage to health caused by intimate partner violence demands effective
responses from healthcare providers and healthcare systems worldwide. To date,
most evidence for the few existing, effective interventions in use comes from
high-income countries. Gupta et al. provide rare evidence of a nurse-delivered
intimate partner violence screening, supportive care and referral intervention
from a large-scale randomised trial in Mexican public health clinics. No
difference was found in the primary outcome of reduction in intimate partner
violence. There were significant short-term benefits in safety planning and
mental health (secondary outcomes) for women in the intervention arm, but these
were not sustained.This important study highlights the challenges of primary
outcome choices in such studies, and further challenges for the sustainability of
healthcare systems and healthcare provider interventions. These challenges
include the role of theory for sustainability and the risk that baseline measures
of intimate partner violence can wash out intervention effects. We emphasise the
importance of studying the processes of adaptation, integration and coordination
in the context of the wider healthcare system.Please see related article:
https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-017-0880-y.
PMID- 28697811
TI - Effect of an intervention in storm drains to prevent Aedes aegypti reproduction
in Salvador, Brazil.
AB - BACKGROUND: Aedes aegypti, the principal vector for dengue, chikungunya and Zika
viruses, is a synanthropic species that uses stagnant water to complete its
reproductive cycle. In urban settings, rainfall water draining structures, such
as storm drains, may retain water and serve as a larval development site for
Aedes spp. reproduction. Herein, we describe the effect of a community-based
intervention on preventing standing water accumulation in storm drains and their
consequent infestation by adult and immature Ae. aegypti and other mosquitoes.
METHODS: Between April and May of 2016, local residents association of Salvador,
Brazil, after being informed of water accumulation and Ae. aegypti infestation in
the storm drains in their area, performed an intervention on 52 storm drains. The
intervention consisted of placing concrete at the bottom of the storm drains to
elevate their base to the level of the outflow tube, avoiding water accumulation,
and placement of a metal mesh covering the outflow tube to avoid its clogging
with debris. To determine the impact of the intervention, we compared the
frequency at which the 52 storm drains contained water, as well as adult and
immature mosquitoes using data from two surveys performed before and two surveys
performed after the intervention. RESULTS: During the pre-intervention period,
water accumulated in 48 (92.3%) of the storm drains, and immature Ae. aegypti
were found in 11 (21.2%) and adults in 10 (19.2%). After the intervention, water
accumulated in 5 (9.6%) of the storm drains (P < 0.001), none (0.0%) had
immatures (P < 0.001), and 3 (5.8%) contained adults (P = 0.039). The total
number of Ae. aegypti immatures collected decreased from 109 to 0 (P < 0.001) and
adults decreased from 37 to 8 (P = 0.011) after the intervention. Collection of
immature and adult non-Aedes mosquitoes (mainly Culex spp.) in the storm drains
also decreased after the intervention. CONCLUSION: This study exemplifies how a
simple intervention targeting storm drains can result in a major reduction of
water retention, and, consequently, impact Ae. aegypti larval populations. Larger
and multi-center evaluations are needed to confirm the potential of citywide
structural modifications of storm drains to reduce Aedes spp. infestation level.
PMID- 28697812
TI - Imaging and lipidomics methods for lipid analysis in metabolic and cardiovascular
disease.
AB - Cardiometabolic diseases exhibit changes in lipid biology, which is important as
lipids have critical roles in membrane architecture, signalling, hormone
synthesis, homoeostasis and metabolism. However, Developmental Origins of Health
and Disease studies of cardiometabolic disease rarely include analysis of lipids.
This short review highlights some examples of lipid pathology and then explores
the technology available for analysing lipids, focussing on the need to develop
imaging modalities for intracellular lipids. Analytical methods for studying
interactions between the complex endocrine and intracellular signalling pathways
that regulate lipid metabolism have been critical in expanding our understanding
of how cardiometabolic diseases develop in association with obesity and dietary
factors. Biochemical methods can be used to generate detailed lipid profiles to
establish links between lifestyle factors and metabolic signalling pathways and
determine how changes in specific lipid subtypes in plasma and homogenized tissue
are associated with disease progression. New imaging modalities enable the
specific visualization of intracellular lipid traffic and distribution in situ.
These techniques provide a dynamic picture of the interactions between lipid
storage, mobilization and signalling, which operate during normal cell function
and are altered in many important diseases. The development of methods for
imaging intracellular lipids can provide a dynamic real-time picture of how
lipids are involved in complex signalling and other cell biology pathways; and
how they ultimately regulate metabolic function/homoeostasis during early
development. Some imaging modalities have the potential to be adapted for in vivo
applications, and may enable the direct visualization of progression of
pathogenesis of cardiometabolic disease after poor growth in early life.
PMID- 28697813
TI - Multilocus sequence typing and clonal population genetic structure of Cyclospora
cayetanensis in humans.
AB - To investigate the prevalence of Cyclospora cayetanensis in a longitudinal study
and to conduct a population genetic analysis, fecal specimens from 6579 patients
were collected during the cyclosporiasis - prevalent seasons in two urban areas
of central China in 2011-2015. The overall incidence of C. cayetanensis infection
was 1.2% (76/6579): 1.6% (50/3173) in Zhengzhou and 0.8% (26/3406) in Kaifeng (P
0.05). All the isolates clustered in the C. cayetanensis clade based on the small
subunit ribosomal RNA gene sequence phylogenetic analysis. There were 45
specimens positive for all the five C. cayetanensis microsatellite loci, and
formed 29 multilocus genotypes (MLGs). The phylogenetic relationships of 54
distinct MLGs (including 25 known reference MLGs), based on the concatenated
multilocus sequences, formed three main clusters. A population structure analysis
showed that the 79 isolates (including 34 known reference isolates) of C.
cayetanensis produced three distinct subpopulations based on allelic profile
data. In conclusion, we determined the frequency of C. cayetanensis infection in
humans in Henan Province. The clonal population structure of the human C.
cayetanensis isolates showed linkage disequilibrium and three distinct
subpopulations.
PMID- 28697814
TI - Antiprotozoal effects of metal nanoparticles against Ichthyophthirius
multifiliis.
AB - Ichthyophthirius multifiliis is a widespread, ciliated protozoan ectoparasite of
fish. In the present study, we investigated the effects of metal nanoparticles on
the reproduction and infectivity of free-living stages of I. multifiliis. We
determined that ~50% of theronts could be killed within 30 min of exposure to
either 20 ng mL-1 gold, 10 ng mL-1 silver or 5 ng mL-1 zinc oxide nanoparticles.
Silver and zinc oxide nanoparticles at concentration of 10 and 5 ng mL-1 killed
100 and 97% of theronts, respectively and inhibited reproduction of tomonts after
2 h exposure. Gold nanoparticles at 20 ng mL killed 80 and 78% of tomonts and
theronts 2 h post exposure, respectively. In vivo exposure studies using rainbow
trout (Oncoryhnchus mykiss) demonstrated that theronts, which survived zinc oxide
nanoparticles exposure, showed reduced infectivity compared with control
theronts. No mortalities were recorded in the fish groups cohabited with theronts
exposed to either nanoparticles compared with 100% mortality in the control
group. On the basis of the results obtained from this study, metal nanoparticles
particularly silver nanoparticles hold the best promise for the development of
effective antiprotozoal agents useful in the management of ichthyophthiriosis in
aquaculture.
PMID- 28697815
TI - Phylogeny and morphology of Ovipleistophora diplostomuri n. sp. (Microsporidia)
with a unique dual-host tropism for bluegill sunfish and the digenean parasite
Posthodiplostomum minimum (Strigeatida).
AB - Microsporidia are diverse opportunistic parasites abundant in aquatic organisms
with some species hyperparasitic in digenean parasites. In the current study, we
describe a unique microsporidian parasite, Ovipleistophora diplostomuri n. sp.
that has a tropism for both the bluegill sunfish Lepomis macrochirus, and its
digenean parasite Posthodiplostomum minimum. Though the microsporidium first
infects a fish, the subsequent infection causes hypertrophy of the metacercarial
wall and degeneration of the P. minimum metacercariae within the fish tissue.
Genetic analysis placed this species within Ovipleistophora and ultrastructural
characteristics were consistent with the genus, including the presence of
dimorphic spores within sporophorous vesicles. Meronts did not have a surface
coat of dense material, which has been previously reported for the genus. This is
the first Ovipleistophora species described that does not have a tropism for
ovary. Genetics demonstrated that O. diplostomuri n. sp. groups closely within
fish microsporidia and not other species known to be hyperparasitic in digeneans,
suggesting that it evolved from fish-infecting microsporidians and developed a
secondary tropism for a common and widespread digenean parasite. The high genetic
identity to Ovipleistophora species demonstrates the close relationship of this
unique microsporidian with other microsporidia that infect ovary.
PMID- 28697816
TI - Association between maternal vitamin D status in pregnancy and neurodevelopmental
outcomes in childhood: results from the Avon Longitudinal Study of Parents and
Children (ALSPAC).
AB - Seafood intake in pregnancy has been positively associated with childhood
cognitive outcomes which could potentially relate to the high vitamin D content
of oily fish. However, whether higher maternal vitamin D status (serum 25
hydroxyvitamin D (25(OH)D)) in pregnancy is associated with a reduced risk of
offspring suboptimal neurodevelopmental outcomes is unclear. A total of 7065
mother-child pairs were studied from the Avon Longitudinal Study of Parents and
Children cohort who had data for both serum total 25(OH)D concentration in
pregnancy and at least one measure of offspring neurodevelopment (pre-school
development at 6-42 months; 'Strengths and Difficulties Questionnaire' scores at
7 years; intelligence quotient (IQ) at 8 years; reading ability at 9 years).
After adjustment for confounders, children of vitamin D-deficient mothers (<50.0
nmol/l) were more likely to have scores in the lowest quartile for gross-motor
development at 30 months (OR 1.20; 95 % CI 1.03, 1.40), fine-motor development at
30 months (OR 1.23; 95 % CI 1.05, 1.44) and social development at 42 months (OR
1.20; 95 % CI 1.01, 1.41) than vitamin D-sufficient mothers (>=50.0 nmol/l). No
associations were found with neurodevelopmental outcomes, including IQ, measured
at older ages. However, our results suggest that deficient maternal vitamin D
status in pregnancy may have adverse effects on some measures of motor and social
development in children under 4 years. Prevention of vitamin D deficiency may be
important for preventing suboptimal development in the first 4 years of life.
PMID- 28697817
TI - Effects of maternal nutrient restriction during early or mid-gestation without
realimentation on maternal physiology and foetal growth and development in beef
cattle.
AB - The aim of this study is to determine the effects of early and mid-gestation
nutrient restriction on maternal metabolites and foetal growth. Primiparous Angus
cows were synchronized and inseminated with semen from one sire. Dietary
treatments were: control to gain 1 kg/week (CON) or 0.55% maintenance energy and
CP requirements (nutrient restricted; NR). A subset of dams was fed NR (n=8) or
CON (n=8) from days 30 to 110 of gestation. Another group was fed CON (n=8), days
30 to 190; NR (n=7), days 30 to 110 followed by CON days 110 to 190; or CON,
(n=7) days 30 to 110 followed by NR days 110 to 190. Cows were harvested at days
110 or 190 of gestation, when foetal measurements and samples were collected.
Cows that were NR during days 30 to 110 or 110 to 190 of gestation lost
significant BW and body condition score (P<0.001), this was associated with
reduced plasma glucose during NR (P<0.002). Foetal weights, empty foetal weights,
abdominal and thoracic circumferences were all reduced (P<0.03) in day 110 NR
animals. Foetal perirenal adipose as a percentage of empty foetal weight was
increased (P=0.01) in NR day 110 female foetuses compared with CON foetus.
Maternal serum triglycerides at day 110 of gestation were decreased (P<0.05) in
NR dams, whereas foetal serum triglycerides were increased (P<0.05) in response
to maternal NR. Foetal weights tended to be reduced (P=0.08) in NR/CON and CON/NR
v. CON/CON cattle at day 190 of gestation. Empty foetal weights, abdominal and
thoracic circumferences were reduced (P?0.03) in NR/CON and CON/NR v. CON/CON
cattle. Brain weight as a percentage of empty foetal weight was increased
(P<0.001) in NR/CON and CON/NR v. CON/CON cattle. Foetal perirenal adipose as a
percentage of empty foetal weight was increased (P=0.003) in NR/CON and CON/NR v.
CON/CON cattle. Maternal serum triglycerides at day 190 of gestation were
decreased (P<0.05) in association with maternal NR. Foetal serum triglycerides at
day 190 of gestation were increased (P<0.05) in response to maternal NR during
early gestation but decreased by NR in mid gestation compared with CON foetuses.
The data show that maternal nutrient restriction during early or mid-gestation
cause's asymmetrical foetal growth restriction, regardless if the restriction is
preceded or followed by a period of non-restriction.
PMID- 28697818
TI - Speciation in the genus Cloacina (Nematoda: Strongylida): species flocks and
intra-host speciation.
AB - Sequences of the first and second internal transcribed spacers (ITS1 + ITS2) of
nuclear ribosomal DNA were employed to determine whether the congeneric
assemblages of species of the strongyloid nematode genus Cloacina, found in the
forestomachs of individual species of kangaroos and wallabies (Marsupialia:
Macropodidae), considered to represent species flocks, were monophyletic.
Nematode assemblages examined in the black-striped wallaby, Macropus
(Notamacropus) dorsalis, the wallaroos, Macropus (Osphranter)
antilopinus/robustus, rock wallabies, Petrogale spp., the quokka, Setonix
brachyurus, and the swamp wallaby, Wallabia bicolor, were not monophyletic and
appeared to have arisen by host colonization. However, a number of instances of
within-host speciation were detected, suggesting that a variety of methods of
speciation have contributed to the evolution of the complex assemblages of
species present in this genus.
PMID- 28697819
TI - Functional characterization of single-domain cystatin-like cysteine proteinase
inhibitors expressed by the trematode Fasciola hepatica.
AB - Cystatins are small, phylogenetically conserved proteins that are tight-binding
inhibitors of cysteine proteinases. The liver fluke Fasciola hepatica uses a
diverse set of cysteine proteinases of the papain superfamily for host invasion,
immune evasion and nutrition, but little is known about the regulation of these
enzymes. The aim of this work is to characterize the cystatin repertoire of F.
hepatica. For this purpose, we first surveyed the available sequence databases,
identifying three different F. hepatica single-domain cystatins. In agreement
with the in silico predictions, at least three small proteins with cysteine
proteinase binding activity were identified. Phylogenetic analyses showed that
the three cystatins (named FhStf-1, -2 and -3) are members of the I25A subfamily
(stefins). Whereas FhStf-1 grouped with classical stefins, FhStf-2 and 3 fell in
a divergent stefin subgroup unusually featuring signal peptides. Recombinant
rFhStf-1, -2 and -3 had potent inhibitory activity against F. hepatica cathepsin
L cysteine proteinases but differed in their capacity to inhibit mammalian
cathepsin B, L and C. FhStf-1 was localized in the F. hepatica reproductive
organs (testes and ovary), and at the surface lamella of the adult gut, where it
may regulate cysteine proteinases related with reproduction and digestion,
respectively. FhStf-1 was also detected among F. hepatica excretion-secretion
(E/S) products of adult flukes. This suggests that it is secreted by non
classical secretory pathway and that it may interact with host lysosomal cysteine
proteinases.
PMID- 28697820
TI - High Levels of Hand-Hygiene Compliance Are a Worthwhile Pursuit.
PMID- 28697821
TI - The first detection of Toxoplasma gondii DNA in environmental air samples using
gelatine filters, real-time PCR and loop-mediated isothermal (LAMP) assays:
qualitative and quantitative analysis.
AB - Toxoplasma gondii infections are acquired through the ingestion of oocysts
present in the environment. However, there is no data about their occurrence in
the air or about airborne transmission of these infections. In the present paper,
we report on the identification of T. gondii using rapid molecular detection
methods, supported by microscopic analysis, in environmental air samples. A total
of 71 samples were collected, using gelatine filters, from kitchen gardens,
recreational areas and sandpits located in northern and north-eastern Poland.
Material recovered from the filters was analysed using real-time PCR and loop
mediated isothermal assays targeting the T. gondii B1 gene. Toxoplasma gondii DNA
was found in two samples, as confirmed by both molecular assays. Genotyping at
the SAG2 locus showed Toxoplasma SAG2 type I. Moreover, the presence of T. gondii
oocysts was confirmed in one of the positive samples with the use of microscopy.
The results showed that T. gondii may be present in environmental air samples and
that respiratory tract infections may play a role in the high prevalence of
toxoplasmosis in humans and animals. To the best of our knowledge, this is the
first epidemiological evidence that oro-fecal and foodborne toxoplasmosis may be
traceable to an airborne respiratory origin and that this may represent a new,
previously unknown transmission route for this disease.
PMID- 28697822
TI - [Diagnostic value of baseline serum luteinizing hormone level for central
precocious puberty in girls].
AB - OBJECTIVE: To evaluate the diagnostic value of baseline serum luteinizing hormone
(LH) level for central precocious puberty (CPP) in girls. METHODS: A total of 279
girls with precocious puberty were subjected to assessment of growth and
development, bone age determination, baseline LH test, and follicle-stimulating
hormone (FSH) test, gonadotropin-releasing hormone stimulation test, and other
related examinations. Of the 279 patients, 175 were diagnosed with CPP and 104
with premature thelarche (PT). The receiver operating characteristic (ROC) curve
was used to evaluate the diagnostic value of baseline LH and FSH levels and their
peak levels for CPP, and the correlation between the baseline LH level and the
peak LH level was analyzed. RESULTS: The CPP group had significantly higher bone
age, baseline LH and FSH levels, peak LH and FSH levels, and ratio of peak LH
level to peak FSH level than the PT group (P<0.01). The ROC curve proved that
baseline LH level and peak LH level had good diagnostic values for CPP. Among the
three bone age subgroups in the CPP group (7.0-9.0 years, 9.0-11.0 years, and
>11.0 years), baseline LH level showed the best diagnostic value in the >11.0
years subgroup, with the largest area under the ROC curve. At a baseline LH level
of 0.45 IU/L, the Youden index reached the peak value, and the sensitivity and
specificity were 66.7% and 80% respectively, for the diagnosis of CPP. At a peak
LH level of 9.935 IU/L, the Youden index reached the peak value, and the
sensitivity and specificity were 74.8% and 100% respectively, for the diagnosis
of CPP. The baseline LH level was positively correlated with the peak LH level
(r=0.440, P<0.01). CONCLUSIONS: Baseline LH level can be used as an primary
screening index for the diagnosis of CPP. It has a certain diagnostic value for
CPP at different bone ages, and may be used as a monitoring index during the
treatment and follow-uP.
PMID- 28697823
TI - [Clinical feature and genetic analysis of a family affected by congenital bile
acid synthesis defect type 2: identification of 2 novel mutations in AKR1D1
gene].
AB - Congenital bile acid synthesis defect type 2 (CBAS2) is an autosomal recessive
disorder caused by biallelic mutations of AKR1D1 gene, which encodes the Delta4-3
oxo-steroid 5beta-reductase. Cholestatic jaundice is the main clinical
manifestation, accompanied by malabsorption of fat and fat-soluble vitamins. This
paper reported the clinical and genetic features of a CBAS2 patient definitely
diagnosed by AKR1D1 genetic analysis. An 8-month-old male infant was referred to
the hospital with the complaint of jaundiced skin and sclera over 7 months. On
physical examination, growth retardation and malnutrition were discovered besides
mild jaundice of the skin and sclera. The liver was palpable 8 cm below the right
subcostal margin with medium texture, and the spleen was not enlarged. On liver
function test, elevated levels of bilirubin (predominantly conjugated bilirubin)
and transaminases were detected, but serum total bile acids and gamma-glutamyl
transpeptidase levels were within the normal ranges. Liver histopathologic
analysis showed disorganized bile ducts, obvious multinucleated giant cells,
significant cholestasis in hepatocytes, together with portal and interstitial
fibrosis and lymphocytic infiltration. Via next generation sequencing analysis
and Sanger sequencing confirmation, the infant proved to be a compound
heterozygote of the AKR1D1 variants c.579+2delT and c.853C>T(p.Q285X), two novel
mutations originated from his mother and father, respectively. CBAS2 was thus
definitely diagnosed, and chenodeoxycholic acid was given orally. As a result,
the abnormal liver function and hepatomegaly were improved gradually. On a follow
up 3 months later, a soft liver was palpable 2.5 cm below the right subcostal
margin, and all liver function indices recovered to normal ranges.
PMID- 28697824
TI - [Analysis of treatment efficacy for congenital hypothyroidism in some regions of
Yunnan Province, China].
AB - OBJECTIVE: To observe the effects of initial doses and treatment timing of
levothyroxine (L-T4) on the clinical efficacy in children with congenital
hypothyroidism (CH). METHODS: This study included 98 children who had an abnormal
level of thyroid stimulating hormone (TSH) in neonatal screening in four regions
of Yunnan Province and who finally had a confirmed diagnosis of CH. They received
treatment with L-T4 and were divided into standard dose group (10-15 MUg/kg per
day) and low dose group (<10 MUg/kg per day) by the therapeutic dose of L-T4.
Meanwhile, these patients were also classified into two treatment groups based on
the starting time of L-T4 treatment, namely under 2 months old group and more
than 2 months old group. The thyroid function and physical and neural development
were examined before and after treatment. RESULTS: Compared with the low dose
group, the standard dose group had a significantly lower TSH level and a
significantly higher free thyroxine (FT4) level at 2 weeks after treatment
(P<0.05). There were no significant differences in TSH and FT4 levels at other
time points after treatment between the standard and low dose groups (P>0.05).
The physical and neural development were not significantly different between the
two dose groups before and at all time points after treatment (P>0.05). At all
time points after treatment, the levels of TSH and FT4 and physical development
were not significantly different between the different starting time groups
(P>0.05). However, the Gesell score was significantly higher in the under 2
months old group than in the more than 2 months old group at all time points
after treatment (P<0.05). CONCLUSIONS: The standard dose group has a better
treatment outcome than the low dose group, whereas the symptoms of
hyperthyroidism deserve close attention. The treatment timing is vital to the
neurodevelopment of children with CH. Once diagnosed, the patients should receive
treatments immediately.
PMID- 28697825
TI - [Screening and follow-up for congenital heart disease in children aged 0-3 years
in rural areas of Chongqing, China].
AB - OBJECTIVE: To examine the incidence of congenital heart disease (CHD) in children
aged 0-3 years in the rural areas of Chongqing, and to determine the suitable
"screening-diagnosis-follow-up" system and screening indicators for CHD in these
areas. METHODS: Children aged 0-3 years from rural areas of the Fuling Disctrict
of Chongqing were selected by cluster sampling. Using the "screening-diagnosis
evaluation system" employed at the levels of village/town, district/county, and
province/city, the children were screened for seven indicators, i.e., family
history of CHD, dyspnea, cyanosis, unique facial features, other congenital
malformations, heart murmurs, and blood oxygen saturation (SpO2<95%). Children
who were positive for one or more indicators accepted echocardiography (ECG) for
the diagnosis of CHD. CHD patients were evaluated for disease progression, given
guided treatments, and followed-up by pediatric cardiologists. RESULTS: Screening
was performed for 10 005 out of the 10 281 children enrolled in the study (97.32%
response rate). Among the 175 children who were positive for the indicators, 166
underwent ECG and 60 (0.60/00) were diagnosed with CHD, including 46 cases of
simple CHD (76.65%), 11 cases of combined CHD (18.33%), and 3 cases of complex
CHD (5.00%). Of the 7 screening indicators, heart murmur had the largest area
under the ROC curve for the diagnosis of CHD. In addition, a combination of
screening indicators (heart murmur, unique facial features, and other congenital
malformations) was most effective for screening out CHD. The CHD patients were
given surgical or intervention treatments, and followed up for 6 to 18 months.
Ten patients improved without treatment, 13 patients received interventional or
surgical treatment, 1 patient died of non-cardiac reasons. The remaining 36
patients were subjected to further follow-up. CONCLUSIONS: Heart murmur alone and
in combination with unique facial features and other congenital malformations are
valuable tools for CHD screening in children aged 0-3 years. The "village/town
district/county-province/city" screening-diagnosis-evaluation systems are useful
for the early detection, diagnosis, and treatment of CHD in infants and young
children from the rural areas of Chongqing.
PMID- 28697826
TI - [Risk factors for congenital heart disease in Chinese neonates: a Meta analysis].
AB - OBJECTIVE: To investigate the major risk factors for congenital heart disease
(CHD) in Chinese neonates and to provide a reference for the prevention of CHD.
METHODS: A literature search was performed to collect the case-control studies on
the risk factors for CHD in Chinese neonates published in 2001-2016. The relevant
data were extracted accordingly. The quality of included studies was assessed by
Newcastle-Ottawa Scale. Sensitivity analysis was conducted using different models
to analyze the same data. The publication bias was assessed by Egger's test.
RESULTS: A total of 17 case-control studies involving 2 930 cases and 4 952
controls were included. The Meta analysis showed that the major risk factors for
CHD in Chinese neonates were as follows: mother with advanced age (OR=2.649,
95%CI: 1.675-4.189), cold or fever (OR=4.558, 95%CI: 2.901-7.162), medication use
in early pregnancy (OR=3.961, 95%CI: 2.816-5.573), passive smoking (OR=2.766,
95%CI: 1.982-3.859), abnormal childbearing history (OR=2.992, 95%CI: 1.529
5.856), noise exposure (OR=3.030, 95%CI: 1.476-6.217), radiation exposure
(OR=2.363, 95%CI: 1.212-4.607), decoration (OR=4.979, 95%CI: 3.240-7.653),
gestational diabetes (OR=5.090, 95%CI: 3.132-8.274), and pet raising (OR=2.048,
95%CI: 1.385-3.029). CONCLUSIONS: Mothers with advanced age, cold or fever,
medication use in early pregnancy, passive smoking, abnormal childbearing
history, noise exposure, radiation exposure, decoration, gestational diabetes,
and pet raising may increase the risk of CHD in Chinese neonates.
PMID- 28697827
TI - [Effects of Huaiqihuang granules on immune function in children with severe
Mycoplasma pneumoniae pneumonia].
AB - OBJECTIVE: To observe the effects of Huaiqihuang granules on the immune function
in children with severe Mycoplasma pneumoniae pneumonia. METHODS: Pediatric
inpatients with severe Mycoplasma pneumoniae pneumonia were randomly divided into
Huaiqihuang granule treatment group (n=51) and conventional treatment group
(n=47). The Huaiqihuang granule treatment group was orally administered
Huaiqihuang granules in addition to the conventional treatment, while the
conventional treatment group received conventional treatment only. Levels of
serum IgA, IgG, and IgM, percentages of CD4+ and CD8+ T lymphocyte subsets, and
CD4+/CD8+ ratio were examined in the two groups. The incidence rate of
respiratory tract re-infection within three months following treatment was
compared between the two groups. RESULTS: The levels of serum IgA, IgG, and IgM,
the percentage of CD4+ T lymphocytes, and the CD4+/CD8+ ratio were significantly
higher in the Huaiqihuang granule treatment group than in the conventional
treatment group three months after treatment (P<0.05). In contrast, the
percentage of CD8+ T lymphocytes was significantly lower in the Huaiqihuang
granule treatment group than in the conventional treatment group (P<0.05). In
addition, the incidence rate of respiratory tract re-infection within three
months following treatment was significantly lower in the Huaiqihuang granule
treatment group than in the conventional treatment group (P<0.05). CONCLUSIONS:
Huaiqihuang granules can regulate immune functions and reduce the incidence of
short-term respiratory tract re-infection in children with severe Mycoplasma
pneumoniae pneumonia.
PMID- 28697828
TI - [A molecular epidemiological study of KI polyomavirus and WU polyomavirus in
children with acute respiratory infection in Tianjin, China].
AB - OBJECTIVE: To investigate the relationship of KI polyomavirus (KIPyV) and WU
polyomavirus (WUPyV) with acute respiratory infection in children in Tianjin,
China. METHODS: A total of 3 730 nasopharyngeal secretions were collected from
hospitalized children with acute respiratory infection in Tianjin Children's
Hospital from January 2011 to December 2013. Viral nucleic acid was extracted,
and virus infection (KIPyV and WUPyV) was determined by PCR. Some KIPyV-positive
and WUPyV-positive PCR products were subjected to sequencing. Sequencing results
were aligned with the known gene sequences of KIPyV and WUPyV to construct a
phylogenetic tree. Amplified VP1 fragments of KIPyV were inserted into the
cloning vector (PUCm-T) transformed into E. coli competent cells. Positive clones
were identified by PCR and sequencing. The nucleotide sequences were submitted to
GenBank. In addition, another seven common respiratory viruses in all samples
were detected by direct immunofluorescence assay. RESULTS: In the 3 730
specimens, the KIPyV-positive rate was 12.14% (453/3 730) and the WUPyV-positive
rate was 1.69% (63/3 730). The mean infection rate of KIPyV was significantly
higher in June and July, while the mean infection rate of WUPyV peaked in
February and March. Most of the KIPyV-positive or WUPyV-positive children were <3
years. The co-infections with KIPyV, WUPyV, and other respiratory viruses were
observed in the children. The co-infection rate was 2.31% (86/3 730) and there
were nine cases of co-infections with WUPyV and KIPyV. Thirty-five KIPyV-positive
and twelve WUPyV-positive PCR products were sequenced and the alignment analysis
showed that they had high homology with the known sequences (94%-100% vs 95%
100%). The VP1 gene sequences obtained from two KIPyV strains in this study were
recorded in GenBank with the accession numbers of KY465925 and KY465926.
CONCLUSIONS: For some children with acute respiratory infection in Tianjin,
China, the acute respiratory infection may be associated with KIPyV and WUPyV
infections. KIPyV infection is common in summer, and WUPyV infection in spring.
The epidemic strains in Tianjin have a high homology with those in other regions.
PMID- 28697829
TI - [Values of combination of urinary L-FABP and NGAL in early diagnosis of acute
kidney injury after cardiac surgery in children].
AB - OBJECTIVE: To investigate the values of combination of urinary liver-type fatty
acid-binding protein (L-FABP) and neutrophil gelatinase-associated lipocalin
(NGAL) in early diagnosis of acute kidney injury (AKI) after cardiac surgery in
children. METHODS: A total of 97 children with congenital heart disease
undergoing cardiopulmonary bypass surgery were enrolled. Serum and urine samples
were collected before and after surgery. Levels of serum creatinine (Scr),
urinary L-FABP, and urinary NGAL from AKI group (n=18) and non-AKI group (n=79)
were measured, and the postoperative dynamic changes in these markers were
compared between the two groups. The receiver operating characteristic (ROC)
curve and the area under ROC curve (AUC) were used to assess the values of these
markers alone or in combination in the prediction of postoperative AKI. RESULTS:
The levels of urinary L-FABP and NGAL in the AKI group were significantly higher
than those in the non-AKI group at 2 and 6 hours after surgery, and the changes
in their concentrations were earlier than Scr. The AUCs of urinary L-FABP alone
in predicting AKI at 2 and 6 hours after surgery were 0.921 and 0.896
respectively, and those of urinary NGAL alone were 0.908 and 0.928 respectively.
Those of their combination were 0.942 and 0.929 respectively. CONCLUSIONS:
Urinary L-FABP and NGAL significantly increase in the early stage of AKI after
cardiac surgery in children, which are significantly earlier than the changes in
Scr. They can be used to predict the occurrence of AKI in the early stage. A
combination of the two biomarkers can further improve the accuracy of diagnosis.
PMID- 28697830
TI - [Value of serum miR-17-92 cluster in diagnosis of retinoblastoma].
AB - OBJECTIVE: To investigate the value of serum miR-17-92 cluster in the diagnosis
of retinoblastoma (RB). METHODS: Serum samples were collected from 20 children
with RB and 20 healthy controls. Quantitative real-time PCR was used to measure
the expression of miR-17-92 cluster. The expression of miR-17-92 cluster was
compared between children with different stages of RB and the changes in the
expression of miR-17-92 cluster after multimodality therapy were analyzed. The
receiver operating characteristic (ROC) curve was used to investigate the value
of serum miR-17-92 cluster in the diagnosis of RB. RESULTS: Compared with the
healthy controls, the children with RB had significantly higher relative
expression of miR-17-3P, miR-17-5P, miR-18a, and miR-20a in serum (P<0.05), and
miR-18a showed the greatest increase. There were no significant differences in
the relative expression of miR-19a, miR-19b-1, and miR-92a-1 between children
with RB and healthy controls (P>0.05). There were no significant differences in
the expression of miR-17-5P, miR-17-3P, miR-18a, and miR-20a between the children
with early-to-moderate stage of RB and those with advanced stage of RB (P>0.05),
but there were significant reductions after multimodality therapy (P<0.05). In
the diagnosis of RB, the areas under the ROC curve (AUCs) for serum miR-17-3P,
miR-17-5P, miR-18a, and miR-20a were 0.770, 0.755, 0.828, and 0.665 respectively,
and miR-18a had the largest AUC, with a sensitivity of 90% and a specificity of
65%. CONCLUSIONS: miR-17-3P, miR-17-5P, miR-18a, and miR-20a are highly expressed
in the serum of children with RB, and miR-18a may be used as a new marker for the
diagnosis of RB.
PMID- 28697831
TI - [Adverse effects of high-dose methotrexate therapy].
AB - OBJECTIVE: To investigate the adverse effects of high-dose methotrexate (HDMTX)
therapy, and to provide a theoretical basis for optimizing clinical treatment.
METHODS: A retrospective analysis was performed for the clinical data of 120
children with acute lymphoblastic leukemia or non-Hodgkin lymphoma who underwent
601 times of HDMTX therapy. The adverse effects of various systems were analyzed
according to the WHO criteria for the classification of adverse effects of
anticancer drugs. RESULTS: Almost all the children experienced bone marrow
suppression, and 93.3% had granulocytopenia. The most common adverse effects in
the digestive system and urinary system were elevated glutamic-pyruvic
transaminase (60.4%) and proteinuria (9.2%) respectively. For skin symptoms, skin
erythema had the highest incidence rate (7.2%). The adverse effects in the
nervous system (hyperpathia, numbness of extremities, or headache) were only
observed in 7 cases. Serious adverse effects were only seen in the blood system
and digestive system. Compared with the 3 g/m2 methotrexate (MTX) group, the 5
g/m2 HDMTX group had a significantly higher 24-hour plasma MTX concentration,
significant reductions in hemoglobin and platelet count, and significantly higher
incidence rates of oral mucositis, proteinuria, and skin symptoms (P<0.05).
CONCLUSIONS: Serious adverse effects of HDMTX therapy mainly involve the blood
system and digestive system, and the adverse effects such as bone marrow
suppression, oral mucositis, proteinuria, and skin symptoms occur in a dose
dependent manner.
PMID- 28697832
TI - [Efficacy of clonidine transdermal patch in treatment of moderate to severe tic
disorders in children].
AB - OBJECTIVE: To investigate the difference in the efficacy between clonidine
transdermal patch and haloperidol tablets in the treatment of moderate to severe
tic disorders in children. METHODS: A total of 134 children with moderate to
severe tic disorders were randomly divided into clonidine group (n=70) and
haloperidol group (n=64). The clonidine and haloperidol groups were treated with
clonidine transdermal patch and haloperidol tablets respectively, and the
treatment lasted for 8 weeks in both groups. The Yale Global Tic Severity Scale
(YGTSS) was used to evaluate the conditions of the children before and after
treatment, and the adverse events during the treatment were recorded. RESULTS:
The haloperidol group had a significantly better treatment outcome than the
clonidine group after one week of treatment (P<0.05); the treatment outcome
showed no significant difference between the two groups after 3, 5, and 8 weeks
of treatment (P>0.05). The clonidine group had significantly less reductions in
the motor tics, vocal tics, and function impairment scores and total score of
YGTSS than the haloperidol group after one week of treatment (P<0.05); there were
no significant differences in YGTSS score reductions between the two groups after
3, 5, and 8 weeks of treatment (P>0.05). The clonidine group had a significantly
lower overall incidence of adverse events than the haloperidol group (8% vs 37%;
P<0.01). CONCLUSIONS: Clonidine transdermal patch and haloperidol are both
effective in the treatment of moderate to severe tic disorders in children. The
clonidine transdermal patch, despite slow action, has comparable efficacy and
fewer adverse effects compared with haloperidol.
PMID- 28697833
TI - [Clinical characteristics of urticaria in children versus adults].
AB - OBJECTIVE: To study the clinical characteristics of urticaria in children versus
adults, and to provide reference for the etiological analysis, disease
evaluation, and treatment of urticaria in children. METHODS: The clinical data of
2 411 patients with urticaria who visited the Department of Dermatology at
Xiangya Hospital of Central South University from January 2013 to May 2017 were
collected to study their socio-demographic characteristics. The clinical
characteristics of urticaria were compared between the 68 children and 672 adults
of the 740 patients with complete follow-up data. RESULTS: Among the 411
pediatric patients, 314 (76.4%) had acute urticaria; among the 2 000 adult
patients, 896 (44.8%) had chronic spontaneous urticaria. The causes of acute
urticaria in children included infection (41%, 16/39). The accompanying symptoms
of acute urticaria in children mainly included abdominal pain and diarrhea (44%,
17/39), while those in adults mainly included chest distress and shortness of
breath (32%, 11/34). Compared with the adult patients, the pediatric patients had
significantly lower chronic urticaria activity scores before and after treatment
(P<0.05), a significantly higher rate of response to second-generation
antihistamines (82.1% vs 62.2%; P<0.05), and a significantly higher proportion of
individuals with a personal and family history of urticaria (P<0.05).
CONCLUSIONS: Acute urticaria is more commonly seen than chronic urticaria in
children with urticaria, and the main accompanying symptoms are abdominal pain
and diarrhea, which are different from adults with urticaria. Chronic urticaria
has a better treatment outcome in children than in adults. The most frequently
seen cause of acute urticaria is infection in children. Atopic children may be
susceptible to urticaria.
PMID- 28697834
TI - [Association of serum vitamin D level with severity and treatment in children
with Henoch-Schonlein purpura].
AB - OBJECTIVE: To investigate the association of serum vitamin D [25-(OH)D3] level
with the severity and treatment in children with Henoch-Schonlein purpura (HSP).
METHODS: A total of 50 children with newly-diagnosed HSP between January and
December, 2015 were enrolled as HSP group, and 49 healthy children were enrolled
as control group. Fasting serum samples were collected, and ELISA was used to
measure serum 25-(OH)D3 level. According to the serum 25-(OH)D3 level, the HSP
group were further divided into normal group (>20 ng/mL) (n=9), insufficiency
group (15-20 ng/mL) (n=15), deficiency group (<=15 ng/mL) (n=25), and severe
deficiency group (<=5 ng/mL) (n=1). The general data, clinical manifestations,
hormone therapy, course of disease before admission, and length of hospital stay
were compared between groups. RESULTS: The HSP group had a significantly lower
serum 25-(OH)D3 level than the control group (16+/-6 ng/mL vs 29+/-5 ng/mL;
P<0.01). Compared with the normal and insufficiency groups, the deficiency and
severe deficiency groups had significant increases in the incidence rate of renal
involvement, rate of hormone application, and median length of hospital stay
(P<0.05), while there was no significant difference in course of disease before
admission (P>0.05). CONCLUSIONS: Children with HSP have a low serum 25-(OH)D3
level, and such children may have a high risk of renal involvement, a high rate
of hormone application, and a prolonged length of hospital stay. However, further
studies are needed to investigate whether vitamin D supplementation is helpful to
the treatment of HSP and can shorten the course of disease in children with HSP.
PMID- 28697835
TI - [Vitamin D level at birth and influencing factors in preterm infants].
AB - OBJECTIVE: To investigate vitamin D level at birth and possible influencing
factors in preterm infants. METHODS: A total of 600 preterm infants were
enrolled, and venous blood samples were collected within 24 hours after birth to
measure the serum level of 25-hydroxyvitamin D [25(OH)D]. The effect of sex,
birth weight, birth season, gestational age, mother's age, body mass index (BMI)
in early pregnancy, delivery mode, and complications during pregnancy on serum
25(OH)D level was analyzed. RESULTS: The rates of vitamin D deficiency,
insufficiency, and sufficiency were 42.0%, 38.7%, and 19.3% respectively. The
preterm infants born in summer and autumn had a significantly higher serum
25(OH)D level than those born in winter (P<0.05) and a significantly lower
incidence rate of vitamin D deficiency than those born in spring and winter
(P<0.003). Compared with those whose mothers were aged <30 years, the infants
whose mothers were aged >=30 years had a significantly higher serum 25(OH)D level
(P<0.05) and a significantly lower incidence rate of vitamin D deficiency
(P<0.017). Compared with those whose mothers were overweight or had normal body
weight, the infants whose mothers were obese had a significantly lower serum
25(OH)D level (P<0.05) and a significantly higher incidence rate of vitamin D
deficiency (P<0.006). Compared with those whose mothers had no preeclampsia, the
infants whose mothers had preeclampsia during pregnancy had a significantly lower
serum 25(OH)D level (P<0.05) and a significantly higher incidence rate of vitamin
D deficiency (P<0.017). The multivariate analysis showed that birth in winter and
spring, mother's age <30 years, and early-pregnancy BMI >=28 kg/m2 were risk
factors for vitamin D deficiency (P<0.05). CONCLUSIONS: There is a high
prevalence of vitamin D deficiency in preterm infants. Vitamin D supplementation
should be given to the preterm infants with high-risk factors for vitamin D
deficiency.
PMID- 28697836
TI - [Association between IL-6 C-572G and susceptibility to spontaneous preterm
birth].
AB - OBJECTIVE: To investigate the association between the genetic polymorphism of IL
6 C-572G and susceptibility to spontaneous preterm birth (SPTB). METHODS: The
subjects were from Beijing and the surrounding areas of Beijing. This case
control study enrolled 569 SPTB infants, including 56 extremely preterm (<28
weeks of gestation), 166 very preterm (28-31+6 weeks of gestation) and 347
moderate to late preterm infants (32 to 36+6 weeks of gestation). A total of 673
term infants were enrolled as the control group. The latest Sequenom
MassARRAY(r)SNP detection technique was used for the typing of single nucleotide
polymorphism of IL-6 C-572G. RESULTS: Compared with the CC genotypes, the IL-6 C
572G G-positive genotype (CG+GG genotype) was significantly associated with an
increased susceptibility to moderate to late SPTB (OR=1.35, 95%CI: 1.01-1.80,
P=0.04). CONCLUSIONS: Among the Chinese population, IL-6 C-572G polymorphism is
associated with susceptibility to moderate to late SPTB.
PMID- 28697837
TI - [Poor weight gain, recurrent metabolic alkalosis and hypokalemia in a neonate].
AB - The study reports a female neonate with a gestational age of 29+2 weeks and a
birth weight of 1 210 g. Ten minutes after birth, the neonate was admitted to the
hospital due to shortness of breath. Several days after birth, the neonate
presented with hyperglycemia, polyuria, and poor weight gain, accompanied by
azotemia, hypochloremic metabolic alkalosis, hypokalemia, and hyponatremia.
Laboratory examinations showed elevated levels of aldosterone, renin, and
angiotensin II. Gene detection revealed SLC12A1 gene mutation. Neonatal Bartter
syndrome was thus confirmed. The neonate was treated with sodium and potassium
supplements, and was followed up for 8 months. During the follow-up, the mental
and neural development of the neonate was almost normal at the corrected age, and
regular reexaminations showed slight metabolic alkalosis and almost normal
electrolyte levels. For the neonates who have the symptoms of unexplainable
polyurine and electrolyte disorders, it is important to examine the levels of
aldosterone, renin and angiotensin. A definite diagnosis of neonatal Bartter
syndrome can be made based on the presence of SLC12A1 gene mutation.
PMID- 28697838
TI - [Hypertension and intermittent convulsions for one month in a school-age child].
AB - Childhood polyarteritis nodosa (PAN) is a rare systemic vasculitis and the
delayed diagnosis and treatment will cause high incidence of sequelae and high
mortality. This article reports a girl with childhood PAN due to posterior
reversible encephalopathy syndrome (PRES). The girl aged ten years was admitted
to the hospital due to hypertension and convulsions for one month. She had
complaints of headache, vomiting, and blurred vision before convulsions. At six
months before admission, a mass was observed in the neck. The physical
examination showed that she had hypertension and no abnormal findings in the
central nervous system. The brain magnetic resonance imaging manifested long T1
and T2 signals, high signal intensities on fluid-attenuated inversion recovery
(FLAIR) images, and iso-signal intensity on diffusion-weighted imaging in the
white matter of the left occipital lobe. Therefore, the cause of convulsions was
considered as PRES. Mass biopsy suggested PAN and no findings supported
tuberculosis. The right kidney atrophy was observed by ultrasound examination.
Emission computed tomography of the kidney showed multiple vascular stenosis and
no blood perfusion in the right kidney, so PAN was confirmed. These findings
suggest that PAN should be considered in patients with vasculitis who had
involvements of multiple systems after excluding common vasculitis, such as
Kawasaki disease and Henoch-Schonlein purpura. Biopsy and angiography should be
performed as early as possible for timely diagnosis and treatment.
PMID- 28697839
TI - [Effect of annexin A2 on EGFR/NF-kappaB signal transduction and mucin expression
in human airway epithelial cells treated with Mycoplasma pneumoniae].
AB - OBJECTIVE: To investigate the effect of annexin A2 (AnxA2) on epithelial growth
factor receptor (EGFR)/nuclear factor-kappaB (NF-kappaB) signal transduction and
mucin expression in human airway epithelial H292 cells treated with Mycoplasma
pneumoniae (MP). METHODS: H292 cells were divided into control group, MP group,
NC-siRNA+MP group, and AnxA2 siRNA+MP group. The cells in the MP group were
incubated with 5 MUg/mL MP antigen for 2 hours. The cells in the NC-siRNA+MP and
AnxA2 siRNA+MP groups were transfected with NC-siRNA and AnxA2 siRNA for 24
hours, followed by MP antigen stimulation for 2 hours. The MTT method was used to
measure cell viability; quantitative real-time PCR was used to measure the mRNA
expression of AnxA2; Western blot was used to measure the protein expression of
AnxA2, phosphorylated EGFR (p-EGFR), and phosphorylated p65 NF-kappaB (p-p65 NF
kappaB); ELISA was used to measure the secretion of mucin 5AC (MUC5AC) and mucin
5B (MUC5B). RESULTS: The MP and NC-siRNA+MP groups had lower cell viability than
the control group (P<0.05). The AnxA2 siRNA+MP group had higher cell viability
than the MP and NC-siRNA+MP groups and lower cell viability than the control
group (P<0.05). The MP and NC-siRNA+MP groups had significantly higher mRNA and
protein expression of AnxA2 than the AnxA2 siRNA+MP group (P<0.05). Compared with
the control group, the MP and NC-siRNA+MP groups had significant increases in the
protein expression of p-EGFR, p-p65 NF-kappaB, MUC5AC, and MUC5B (P<0.05); the
AnxA2 siRNA+MP group had lower protein expression than the MP and NC-siRNA+MP
groups, but higher protein expression than the control group (P<0.05).
CONCLUSIONS: AnxA2 is involved in the airway lesion induced by MP antigen via
mediating EGFR/NF-kappaB signaling activation and mucin expression in human
airway epithelial cells.
PMID- 28697840
TI - [Effect of high-fat diet on expression of transient receptor potential vanilloid
1 in respiratory tract and dorsal root ganglion of mice].
AB - OBJECTIVE: To investigate the effect of high-fat diet on the expression of
transient receptor potential vanilloid 1 (TRPV1) in the respiratory system and
the dorsal root ganglion (DRG) of mice, as well as its effect on the excitability
of sensory neurons. METHODS: A total of 20 C57BL/6 mice were randomly divided
into normal-diet (ND) group and high-fat diet (HFD) group, with 10 mice in each
group. The mice were given corresponding diets and body weights were monitored.
After 7 weeks of feeding, lung tissue, bronchial tissue, and DRG at thoracic
segments 3-4 were collected and immunohistochemical staining was performed. A
patch clamp was used to measure the number of action potentials and TRPV1 current
intensity in the DRG. RESULTS: After 7 weeks of feeding, the HFD group had
significantly greater mean weight gain than the ND group (6.4+/-2.6 g vs 2.3+/
0.5 g; P<0.001). The HFD group had significantly higher expression of TRPV1 in
the bronchus, pulmonary alveoli, and DRG than the ND group (P<0.05). Compared
with the ND group, the HFD group had significant increases in the TRPV1 current
intensity and number of action potentials in the DRG (P<0.05). CONCLUSIONS: High
fat diet induces a significant increase in body weight and leads to high
expression of TRPV1 and high excitability in the respiratory system and the
peripheral sensory neurons. This suggests that TRPV1 may be an important factor
in the physiopathological mechanisms of bronchial hyperresponsiveness.
PMID- 28697841
TI - [Advances in targeted therapy for childhood acute myeloid leukemia].
AB - At present, acute myeloid leukemia (AML) accounts for about 15%-20% of childhood
acute leukemia. Although overall survival rate is increasing with the help of
risk stratification, stratification of chemotherapy, and supportive treatment,
conventional pharmacotherapy still has a limited clinical effect and certain
limitations in improving remission rate in previously untreated patients and
reducing recurrence after remission. With the development of precision medicine,
the mechanisms of targeted therapy, including abnormal activation of AML-related
signaling pathways and epigenetic modification, have been found in recent years.
Molecular-targeted drugs can therefore act on specific receptors and target genes
to improve clinical effect and the prognosis of AML patients.
PMID- 28697842
TI - [Research advances in immunological pathogenesis of immunoglobulin A vasculitis].
AB - Immunoglobulin A (IgA) vasculitis is the most common leukocytoclastic small
vessel vasculitis in children and mainly involves the small vessels in the skin,
joints, digestive tract, and kidneys. Its pathogenesis is still unclear.
Currently, it is believed that environmental factors can cause autoimmune
dysfunction and lead to the deposition of IgA-containing immune complexes on the
wall of arterioles on the basis of genetic factors. This article reviews the
research advances in the role of immune factors in the pathogenesis of IgA
vasculitis.
PMID- 28697843
TI - UriSwab: an effective transport medium for nucleic acid detection of Chlamydia
trachomatis, Mycoplasma genitalium and Neisseria gonorrhoeae.
AB - : Background Patient self-sampling allows for remote collection and return to
clinic or laboratory by post. Urine samples, although convenient, are challenging
to post. This study evaluated UriSwab (Copan, Brescia, Italy) as a collection and
transport vessel for Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG) and
Mycoplasma genitalium (MG) detection by polymerase chain reaction, compared with
flocked swab and neat urine. METHODS: Five replicates of each specimen type were
prepared from previously characterised urine samples (n=330), stored at room
temperature (RT) or 37 degrees C, then extracted on day 1, 3, 7, 10 and 16
(VERSANT kPCR Sample Prep System, Siemens, Munich, Germany). Crossing thresholds
(Cq) from CT and NG detection (VERSANT CT/GC DNA 1.0 assay kit, Siemens) and MG
detection (real-time polymerase chain reaction assay) were compared using
logistic regression, stratified by sample type, temperature and analyte. Mixed
model statistical techniques were used to assess correlation between repeated
observations. RESULTS: UriSwab showed an increasing trend in Cq values at RT and
37 degrees C for CT and NG, and RT for MG (all P<0.01). UriSwab was not
statistically significantly different to neat urine, except CT at RT (0.83, 95%
confidence interval: 0.51-1.15). Flocked swab similarly showed increasing Cq
values at 37 degrees C for CT, a significant decreasing trend at RT for MG and
increasing trend at 37 degrees C for MG. Flocked swab was not statistically
significantly different from neat urine at RT and 37 degrees C for CT and MG.
CONCLUSION: UriSwab allows transport of urine for CT, NG and MG detection
regardless of storage time or temperature, suggesting that CT and NG are stable
for up to 16 days and MG up to 10 days.
PMID- 28697844
TI - Preoperative predictor of extensive resection for acute appendicitis.
AB - BACKGROUND: Appendectomy has been the preferred treatment of acute appendicitis.
However, extensive resection (ER) such as an ileocecal resection is sometimes
needed. We analyzed the predictive factors of ER. METHODS: This was a
retrospective study of 927 patients with acute appendicitis in 7 years. The data
collected, including demographic characteristics, laboratory tests, computed
tomography (CT) findings and days from onset. RESULTS: ER was performed in 40
patients (4.3%). Age, days from onset, C-reactive protein (CRP), and the presence
of several CT findings were significantly higher in the ER group than others (p <
0.01). In a multivariate analysis, four variables (appendiceal mass, non
visualization of appendix, delayed admission, and CRP) retained statistical
significance as predictors of ER (p < 0.01). CONCLUSIONS: We demonstrated that
the four factors are clinically useful for predicting preoperatively whether or
not ER is required. These may help in management decisions, including surgical
procedure and anesthesia.
PMID- 28697845
TI - Evaluation of Veterans Affairs primary care nurse practitioner residency:
Achievement of competencies.
AB - BACKGROUND: The Institute of Medicine has recommended the establishment of
residency programs for advanced practice nursing graduates. Currently, the
evidence about program effectiveness is limited. PURPOSE: To describe the nurse
practitioner (NP) resident outcomes on seven competency domains established by
the VA Centers of Excellence in Primary Care Education (VA CoEPCE). METHODS: We
evaluated mean NP resident competency self-ratings and mean mentor ratings over
the 12-month program across NP residency programs at five sites. Highest and
lowest rated items and differences between NP resident self-ratings and mentor
ratings were analyzed. RESULTS: Mean NP resident self-ratings and mean mentor
ratings demonstrated statistically significant improvement in all domains (p <
.0001). At 12 months, NP residents were rated by their mentors as able to
practice without supervision in all competency domains. At 1 and 12 months,
clinical, leadership and quality improvement/population management competencies
were the lowest scored domains while patient-centered care, interprofessional
team collaboration, shared decision-making and sustained relationships
competencies were highest. CONCLUSIONS: These results provide initial evidence
for the effectiveness of VA CoEPCE NP residency programs and also highlight areas
of needed improvement.
PMID- 28697846
TI - Similar treatment outcomes when performing endodontic therapy on permanent teeth
in a single visit or multiple visits.
PMID- 28697847
TI - The impact of serum trans fatty acids concentration on plaque vulnerability in
patients with coronary artery disease: Assessment via optical coherence
tomography.
AB - BACKGROUND AND AIMS: Recent epidemiological studies have showed that excessive
intake of trans fatty acids (TFA) can be a residual risk for the development of
coronary artery disease (CAD) even under medical management, including statins.
This study aimed at investigating the association between lipid profile,
including serum TFA concentration, and plaque vulnerability using optical
coherence tomography (OCT). METHODS: The level of serum elaidic acid, a major TFA
component, was measured using gas chromatography in 161 consecutively enrolled
patients with CAD under guideline-directed risk factor management. OCT was
performed to evaluate morphological features of angiographic intermediate
stenosis (30% < diameter of stenosis <70%). OCT data were also used to measure
lipid index (LI), defined as mean lipid arc multiplied by lipid length, and
determine the presence of thin-cap fibroatheroma (TCFA), defined as a lipid-rich
plaque with the smallest fibrous cap thickness <65 MUm and the maximal arc >90
degrees . RESULTS: Among 190 lesions assessed using OCT, 49 TCFAs were detected.
In patients with at least one TCFA lesion, levels of elaidic acid (12.9 +/- 4.9
vs. 10.3 +/- 4.3 MUmol/L, p = 0.001), triglycerides (169 +/- 81 vs. 130 +/- 60
mg/dL, p = 0.005), and remnant-like particle cholesterol (10.4 +/- 6.5 vs. 7.7 +/
4.7 mg/dL, p = 0.005) were higher than in those without TCFAs. Generalized
estimating equations identified elaidic acid level as the independent risk factor
of TCFA. LI had a positive correlation with elaidic acid level (r = 0.173, p =
0.025). CONCLUSIONS: TFA may affect plaque vulnerability in patients with CAD.
Serum TFA concentration may represent another cardiovascular risk factor during
conventional risk factor management.
PMID- 28697848
TI - Roles of RNase P and Its Subunits.
AB - Recent studies show that nuclear RNase P is linked to chromatin structure and
function. Thus, variants of this ribonucleoprotein (RNP) complex bind to
chromatin of small noncoding RNA genes; integrate into initiation complexes of
RNA polymerase (Pol) III; repress histone H3.3 nucleosome deposition; control
tRNA and PIWI-interacting RNA (piRNA) gene clusters for genome defense; and
respond to Werner syndrome helicase (WRN)-related replication stress and DNA
double-strand breaks (DSBs). Likewise, the related RNase MRP and RMRP-TERT
(telomerase reverse transcriptase) are implicated in RNA-dependent RNA
polymerization for chromatin silencing, whereas the telomerase carries out RNA
dependent DNA polymerization for telomere lengthening. Remarkably, the four RNPs
share several protein subunits, including two Alba-like chromatin proteins that
possess DEAD-like and ATPase motifs found in chromatin modifiers and remodelers.
Based on available data, RNase P and related RNPs act in transition processes of
DNA to RNA and vice versa and connect these processes to genome preservation,
including replication, DNA repair, and chromatin remodeling.
PMID- 28697849
TI - Post market surveillance in the german medical device sector - current state and
future perspectives.
AB - Medical devices play a central role in the diagnosis and treatment of diseases
but also bring the potential for adverse events, hazards or malfunction with
serious consequences for patients and users. Medical device manufacturers are
therefore required by law to monitor the performance of medical devices that have
been approved by the competent authorities (post market surveillance). Conducting
a nationwide online-survey in the German medical device sector in Q2/2014 in
order to explore the current status of the use of post market instruments we
obtained a total of 118 complete data sets, for a return rate of 36%. The survey
included manufacturers of different sizes, producing medical devices of all risk
classes. The post market instruments most frequently reported covered the fields
of production monitoring and quality management as well as literature
observation, regulatory vigilance systems, customer knowledge management and
market observation while Post Market Clinical Follow-up and health services
research were being used less for product monitoring. We found significant
differences between the different risk classes of medical devices produced and
the intensity of use of post market instruments. Differences between company size
and the intensity of instruments used were hardly detected. Results may well
contribute to the development of device monitoring which is a crucial element of
the policy and regulatory system to identify device-related safety issues.
PMID- 28697850
TI - Association Between Caffeine Intake and All-Cause and Cause-Specific Mortality: A
Population-Based Prospective Cohort Study.
AB - OBJECTIVE: To assess whether caffeine intake is associated with all-cause and
cause-specific mortality. PATIENTS AND METHODS: We conducted a prospective cohort
study using data from the National Health and Nutrition Examination Survey 1999
2010. Cox proportional hazards models were used to compare the multivariate
adjusted hazard ratios (HRs) of participants with a caffeine intake of 10 to 99,
100 to 199, and 200 mg/d or more with those of participants with a caffeine
intake of less than 10 mg/d. RESULTS: In total, 17,594 participants were
included, and the mean +/- SD and median (interquartile range) follow-up was
6.5+/-2.8 years and 6.4 (3.6-9.5) years, respectively; 17,568 participants
(99.8%) completed the follow-up, and 1310 died. Compared with those who had a
caffeine intake of less than 10 mg/d, HRs and 95% CIs for all-cause mortality
were significantly lower in participants with a caffeine intake of 10 to 99 mg/d
(HR, 0.81; 95% CI, 0.66-1.00; P=.05), 100 to 199 mg/d (HR, 0.63; 95% CI, 0.51
0.78; P<.001), and 200 or more mg/d (HR, 0.69; 95% CI, 0.58-0.83; P<.001). A
similar association was observed in participants who consumed less than 1 cup of
coffee per week, and the HR was lowest in those with a caffeine intake of 100 to
199 mg/d (HR, 0.46; 95% CI, 0.22-0.93). There was no association between caffeine
intake and cardiovascular mortality, whereas the HRs for noncardiovascular
mortality were significantly lower in those with a caffeine intake of 10 to 99
mg/d (HR, 0.74; 95% CI, 0.57-0.95; P=.01), 100 to 199 mg/d (HR, 0.60; 95% CI,
0.46-0.77; P<.001), and 200 or more mg/d (HR, 0.65; 95% CI, 0.53-0.80; P<.001).
CONCLUSION: Moderate caffeine intake was associated with a decreased risk of all
cause mortality, regardless of the presence or absence of coffee consumption.
PMID- 28697851
TI - Incidence and Effects of Seasonality on Nonpurulent Lower Extremity Cellulitis
After the Emergence of Community-Acquired Methicillin-Resistant Staphylococcus
aureus.
AB - Nonpurulent lower extremity cellulitis (NLEC) is a common clinical diagnosis,
with beta-hemolytic streptococci and Staphylococcus aureus considered to be the
most frequent causes. In 1999, the US Public Health Service alerted clinicians to
the presence of community-acquired methicillin-resistant S aureus (CA-MRSA)
infections in 4 children in the upper Midwest. Since then, it has become a well
recognized cause of skin and soft-tissue infections, in particular, skin abscess.
A previous population-based study of NLEC in Olmsted County, Minnesota, reported
an unadjusted incidence rate of 199 per 100,000 person-years in 1999, but it is
unknown whether CA-MRSA subsequently has affected NLEC incidence. We, therefore,
sought to determine the population-based incidence of NLEC since the emergence of
CA-MRSA. Age- and sex-adjusted incidence (per 100,000 persons) of NLEC was 176.6
(95% CI, 151.5-201.7). Incidence differed significantly between sexes with age
adjusted sex-specific rates of 133.3 (95% CI, 104.1-162.5) and 225.8 (95% CI,
183.5-268.0) in females and males, respectively. Seasonal incidence differed,
with rates of 224.6 (95% CI, 180.9-268.4) in warmer months (May-September)
compared with 142.3 (95% CI, 112.8-171.9) in colder months (January-April and
October-December). Despite emergence and nationwide spread of CA-MRSA since 1999
in the United States, the incidence of NLEC in Olmsted County was lower in 2013
than in 1999, particularly in females. This suggests that CA-MRSA is not a
significant cause of NLEC and that NLEC cases are seasonally distributed. These
findings may be important in formulation of empirical therapy for NLEC and in
patient education because many patients with NLEC are prone to recurrent bouts of
this infection.
PMID- 28697852
TI - A multidisciplinary approach to laparoscopic sleeve gastrectomy among multiethnic
adolescents in the United States.
AB - BACKGROUND: Childhood obesity has become a serious public health problem in our
country with a prevalence that is disproportionately higher among minority
groups. Laparoscopic sleeve gastrectomy (LSG) is gaining attention as a safe
bariatric alternative for severely obese adolescents. STUDY DESIGN: A
retrospective study on morbidly obese adolescents that underwent LSG at our
institution from 2009 to 2017. Primary outcomes were weight loss as measured by
change in BMI and percent excess weight loss (%EWL) at 1 year after surgery,
resolution of comorbidities and occurrence of complications. RESULTS: Thirty
eight patients, of whom 71% were female and 74% were ethnic minorities, underwent
LSG between 2009 and 2016. Mean age was 16.8years, mean weight was 132.0kg and
mean BMI was 46.7. There were no surgical complications. Mean %EWL was 19.4%,
27.9%, 37.4%, 44.9%, and 47.7% at 1.5, 3, 6, 9, and 12month follow up visits,
respectively. Comorbidity resolution rates were 100% for hypertension and
nonalcoholic fatty liver disease, 91% for diabetes, 44% for prediabetes, 82% for
dyslipidemia and 89% for OSA. CONCLUSIONS: LSG is an effective and safe method of
treatment of morbid obesity in adolescents as it can significantly decrease
excess body weight and resolve comorbid conditions. Further studies are needed to
investigate the long-term effects of LSG in adolescents. CLINICAL RESEARCH STUDY:
Descriptive case series with prospective database. LEVEL OF EVIDENCE: IV.
PMID- 28697853
TI - Inhibition of ataxia telangiectasia related-3 (ATR) improves therapeutic index in
preclinical models of non-small cell lung cancer (NSCLC) radiotherapy.
AB - BACKGROUND AND PURPOSE: To evaluate the impact of ATR inhibition using AZD6738 in
combination with radiotherapy on the response of non-small cell lung cancer
(NSCLC) tumour models and a murine model of radiation induced fibrosis. MATERIALS
AND METHODS: AZD6738 was evaluated as a monotherapy and in combination with
radiation in vitro and in vivo using A549 and H460 NSCLC models. Radiation
induced pulmonary fibrosis was evaluated by cone beam computed tomography (CBCT)
and histological staining. RESULTS: AZD6738 specifically inhibits ATR kinase and
enhanced radiobiological response in NSCLC models but not in human bronchial
epithelial cells (HBECs) in vitro. Significant tumour growth delay was observed
in cell line derived xenografts (CDXs) of H460 cells (p<0.05) which were less
significant in A549 cells. Combination of AZD6738 with radiotherapy showed no
significant change in lung tissue density by CBCT (p>0.5) and histological
scoring of radiation induced fibrosis (p>0.5). CONCLUSION: Inhibition of ATR with
AZD6738 in combination with radiotherapy increases tumour growth delay without
observable augmentation of late radiation induced toxicity further underpinning
translation towards clinical evaluation in NSCLC.
PMID- 28697854
TI - A prospective study of proton reirradiation for recurrent and secondary soft
tissue sarcoma.
AB - BACKGROUND AND PURPOSE: Proton reirradiation for sarcoma has not been previously
described. We hypothesized that this strategy would provide favorable toxicity
and survival outcomes. MATERIAL AND METHODS: Patients with soft tissue sarcoma in
a previously-irradiated field were enrolled on a prospective trial of proton
reirradiation. The primary endpoint was provider-reported acute toxicity.
Secondary endpoints included late toxicities, local control, and overall
survival. RESULTS: 23 patients underwent proton reirradiation. Median time
between radiation courses was 40.7months (range 10-272). No grade 4-5 toxicities
were observed. One patient (4%) experienced acute grade 3 dysphagia. Common grade
2 acute toxicities were fatigue (26%), anorexia (17%), and urinary incontinence
(13%). There were two grade 3 late wound infections (10%) and one grade 3 late
wound complication (5%). Grade 2 late complications included lymphedema (10%),
fracture (5%), and fibrosis (5%). At a median follow-up of 36months, the 3-year
cumulative incidence of local failure was 41% (95% CI [20-63%]). Median overall
survival and progression-free survival were 44 and 29months, respectively. In
extremity patients, amputation was spared in 7/10 (70%). CONCLUSIONS: Proton
reirradiation of recurrent/secondary soft tissue sarcomas is well tolerated.
While longer follow-up is needed, early survival outcomes in this high-risk
population are encouraging.
PMID- 28697855
TI - Re. "Fruit and vegetable consumption and the risk of depression: A meta
analysis".
PMID- 28697856
TI - Demographic and clinical correlates of substance use disorders in first episode
psychosis.
AB - BACKGROUND: We assessed the prevalence and correlates of lifetime substance use
disorders in people with first episode psychosis using the baseline data from the
Recovery After an Initial Schizophrenia Episode (RAISE) Early Treatment Program
study. METHODS: Research staff assessed 404 first episode patients at 34
community mental health centers across the United States with the Structured
Clinical Interview for DSM-IV for diagnoses of psychotic and substance use
disorders. Logistic regression was used to evaluate the relationships between
participant characteristics and lifetime substance use disorders, followed with
generalized linear mixed-effects regression models to identify unique predictors
of lifetime substance use disorders. RESULTS: Approximately one-third of
participants reported recent alcohol use (36.6%) and cannabis use (30.7%), and
one half (51.7%) met criteria for any lifetime alcohol or drug use disorder.
Lifetime substance use disorders were associated with male gender, White race,
higher excited (hyperactivity, mood lability, impulsivity, hostility, and
uncooperativeness), psychotic and depressive symptoms, less impaired cognition,
and greater perceived stigma. Gender, race, and excited symptoms were the most
consistent unique predictors of lifetime substance use disorders found in
multivariate analyses. CONCLUSIONS: Half of first episode psychosis patients have
co-occurring substance use disorders, which are associated with both more severe
symptoms and greater perceptions of stigma. Programs aiming to serve these
patients must have the skills and clinical strategies to help people with these
unique characteristics.
PMID- 28697857
TI - Corrigendum to "A randomized clinical trial of oral hygiene care programmes
during stroke rehabilitation" [J. Dent. 61 (2017) 48-54].
PMID- 28697858
TI - Accelerated partial breast irradiation for elderly women with early breast
cancer: A compromise between whole breast irradiation and omission of
radiotherapy.
AB - PURPOSE: Regarding adjuvant radiation therapy making decision for elderly women,
Albert (2013) published a nomogram predicting the mastectomy-free survival (MFS)
rate with or without adjuvant irradiation. Based on this approach, we proposed to
investigate the use of accelerated partial breast irradiation (APBI) vs. whole
breast irradiation (WBI) or endocrine therapy alone in elderly low-risk breast
cancer patients. METHODS AND MATERIALS: For each elderly woman treated by
conserving surgery and APBI (multicatheter interstitial high-dose-rate
brachytherapy), 5- and 10-year MFS rates were calculated. For each treated
patient, using the Albert nomogram, we calculated the estimated MFS rates at 5
and 10 years, with and without WBI. Then, we compared the estimated MFS rates
after no irradiation and WBI vs. observed MFS rates after APBI. RESULTS: From
2005 to 2016, 79 patients were treated. Median followup was 96.8 months [68.6
104.9], median age was 77 years [66-89]. Expected 5- and 10-year mastectomy rates
calculated with the Albert nomogram without WBI were 2.95% and 7.25%,
respectively, leading to a 10-year MFS rate of 92.7%. Expected 5- and 10-year
mastectomy rates after WBI were 1.41% and 3.66%, respectively, leading to a 10
year MFS rate of 96.3%. Regarding observed MFS rate, 1 pt (1.3%) experienced a
salvage mastectomy. The 10-year MFS rate after APBI was 97.4% vs. 96.3% after WBI
(p = 1) and 92.7% after no irradiation (p = 0.27). No toxicity Grade 3 or more
was observed. CONCLUSIONS: APBI seems to be an attractive compromise between WBI
and no irradiation for elderly women with early stage breast cancer as far as
local control, quality of life and cost benefit is concerned.
PMID- 28697859
TI - Emergency preparedness for mass gatherings: Lessons of "12.31" stampede in
Shanghai Bund.
AB - According to WHO, one of these mass gatherings with critical risk is stampedes.
Shanghai "12.31" stampede was a preventable tragedy that the government and event
planner hold responsibility for. At the same time, it can be a legacy for
improvement in the future. The government should draw experience on the
implementation of an emergency preparedness system, in order to improve the rapid
emergency response during mass gatherings in the future.
PMID- 28697860
TI - Multimodal Nutritional Management in Primary Total Knee Arthroplasty: A
Randomized Controlled Trial.
AB - BACKGROUND: This study aims at evaluating the effectiveness of a new multimodal
nutritional management (MNM) on albumin (ALB) transfusion, the incidence of
electrolyte disorders, blood loss, perioperative levels of ALB and electrolyte,
length of hospital stay (LOH), and complications in patients following total knee
arthroplasty without tourniquet. METHODS: A total of 162 patients were randomized
to receive either the MNM protocol (n = 81, experimental group) or traditional
protocol (n = 81, control group). The primary outcomes were the rate and amount
of ALB infusion, LOH, total blood loss, maximum hemoglobin drop, allogeneic
transfusion rate, and the incidence of electrolyte disorders. The secondary
outcomes were levels of ALB and electrolyte at different time points and the
incidence of complications. RESULTS: The rate and amount of ALB transfusion
required in MNM group were significantly lower than those in control group (P =
.006, P = .021, respectively). LOH was shorter in MNM group (P < .001). Total
blood loss and maximum hemoglobin drop were similar. The incidence of kaliopenia
and hypocalcemia was lower in MNM group on the first postoperative day (P = .019,
P = .028, respectively). Patients in MNM group had higher levels of ALB, sodium,
potassium, and calcium than those in control group on the first postoperative
day. CONCLUSION: The MNM protocol can effectively low down the amount of ALB
transfusion, the number of patients requiring ALB transfusion, the incidence of
electrolyte disorders, and LOH following primary total knee arthroplasty without
tourniquet. Patients can obtain a smaller decline in ALB, sodium, potassium, and
calcium.
PMID- 28697861
TI - Regional Femoral and Tibial Radiolucency in Cemented Unicompartmental Knee
Arthroplasty and the Relationship to Functional Outcomes.
AB - BACKGROUND: Femoral and tibial radiolucent lines (RLL) after unicompartmental
knee arthroplasty (UKA) can be categorized in physiological and pathological
radiolucencies. Although physiological tibial radiolucency is assessed
extensively in literature, studies reporting femoral radiolucency are lacking.
Therefore, a retrospective study was performed to assess physiological femoral
RLL and its relationship to short-term functional outcomes. METHODS: A total of
352 patients were included who underwent robotic-assisted medial UKA surgery and
received a fixed-bearing metal-backed cemented medial UKA. Radiographic follow-up
consisted of standard anteroposterior and lateral radiographs. Functional
outcomes, using the Western Ontario and McMaster Universities Arthritis Index
questionnaire, of patients with RLL were compared with a matched cohort, based on
gender, age, and body mass index. RESULTS: In this cohort, 101 patients (28.8%)
had physiological regional radiolucency around the femoral (10.3%) and/or tibial
(25.3%) components, of which 6.8% concerned both components. Tibial RLL were more
frequently seen compared with femoral RLL (P < .001). Our data suggest that the
time of onset of femoral radiolucency develops later (1.36 years) than tibial
radiolucency (1.00 years, P = .02). No difference in short-term functional
outcomes was found between the RLL group and the matched cohort group without
radiolucency. CONCLUSION: This study acknowledges that tibial and femoral
physiological radiolucencies may develop after cemented medial UKA. Furthermore,
this was the first study showing that physiological femoral RLL occur later than
tibial RLL. Prospective studies with longer follow-up and larger numbers are
necessary to compare radiolucency in different UKA designs and the relationship
to outcomes.
PMID- 28697862
TI - Acetabular and Femoral Anteversions in Standing Position are Outside the Proposed
Safe Zone After Total Hip Arthroplasty.
AB - BACKGROUND: Although most hip dislocations occur in either standing or sitting
position, the safe zone for implant position is defined for the supine position.
Our goal was to determine preoperative and postoperative pelvis and hip
orientations and whether the safe zone defined in supine position can be used to
assess standing radiographs. METHODS: Preoperative and postoperative three
dimensional EOS images were assessed in 66 total hip arthroplasty patients. None
of the patients had dislocation within the follow-up period (12-36 months). The
acetabular anteversion (both anterior pelvic plane [APP] and patient functional
plane) and the femoral anteversion were measured. The sacral slope, pelvic
version, pelvic inclination, and pelvic incidence were also measured. RESULTS:
Acetabular anteversion increased postoperatively in both APP and patient
functional plane (P <.001). Femoral neck anteversion decreased postoperatively (P
=.0942). Sacral slope was 42.4 degrees (-25.9 degrees to 24 degrees )
preoperatively compared with 40.3 degrees (-4.1 degrees to 64.2 degrees )
postoperatively (P =.013). Pelvic version changed from 15.2 degrees (-10.4
degrees to 43.8 degrees ) to 17.2 degrees (-6 degrees to 46.7 degrees ; P =
0.008). Pelvic inclination was 1.12 degrees (-25.9 degrees to 24 degrees )
before total hip arthroplasty and -1.2 degrees (-40.7 degrees to 23.4 degrees )
postoperatively (P =.005). CONCLUSION: The acetabular and femoral implant
orientations in standing position reside out of the safe zone in most patients.
The APP is not vertical in standing position in most patients due to anterior or
posterior pelvic tilt. The proposed safe zone in supine position may not be a
useful measure in the assessment of standing radiographs of patients with
significant anterior or posterior pelvic tilt. LEVEL OF EVIDENCE: Level IV,
therapeutic case series study.
PMID- 28697863
TI - Intra-articular Application is More Effective Than Intravenous Application of
Tranexamic Acid in Total Knee Arthroplasty: A Prospective Randomized Controlled
Trial.
AB - BACKGROUND: The optimal administration route of tranexamic acid (TXA) in total
knee arthroplasty (TKA), and the effect of TXA on hidden blood loss and total
blood loss are undetermined. The purpose of this study was to compare the
effectiveness of intravenous versus intra-articular application of tranexamic
acid in patients undergoing knee arthroplasty. METHODS: A total of 150 patients
undergoing primary unilateral total knee arthroplasty were randomly distributed
to 3 groups (IV, intra-articular, and control group; each 50 patients) and
administrated TXA (1 g IV and 50 mL intra-articular saline, 1 g intra-articularly
and 50 mL intra-articular saline, and 0 g and 50 mL intra-articular saline,
respectively). The amount of total and hidden blood loss (HBL), drainage,
transfusion, changes in hemoglobin levels, and complications were recorded.
RESULTS: Intra-articular use of TXA reduced more total blood loss (P = .011) and
reduced more total 48 hours drainage volume than IV use of TXA (P < .001). Two
patients received transfusion in IV and control group. No deep venous thrombosis
or other severe complications had occurred. The HBL volume had no significant
difference among the control, IV, and intra-articular groups (708.6 +/- 308.2,
651.7 +/- 302.9, and 625.2 +/- 252.1 mL, respectively; which was 65.6%, 70.8%,
and 81.1% of the total loss). CONCLUSION: Intra-articular administration of TXA
significantly reduced total blood loss and drainage volume to a greater degree
than IV injection in total knee arthroplasty without reduction of HBL.
PMID- 28697864
TI - Porous-Coated Metaphyseal Sleeves for Severe Femoral and Tibial Bone Loss in
Revision TKA.
AB - BACKGROUND: Metaphyseal bone loss is commonly encountered in revision total knee
arthroplasty (TKA). Anderson Orthopaedic Research Institute types 2 and 3 defects
generally require some form of metaphyseal fixation or augmentation. This study
evaluates the midterm results of stepped, porous-coated metaphyseal sleeves in
revision TKA in the setting of severe bone loss. METHODS: Patients who underwent
revision TKA using metaphyseal sleeves from March 2006 to May 2014 at our
institution were identified from a prospective research database. Preoperative
patient characteristics and operative data were reviewed. Postoperative outcomes
were compared with preoperative values. Primary study outcomes included
complications, reoperations, radiographic assessment of sleeve osteointegration,
and survivorship. RESULTS: One hundred sixteen knees (108 patients) underwent
revision TKA with 152 metaphyseal sleeves (111 tibial and 41 femoral). Anderson
Orthopaedic Research Institute defect classification included 5 type 2A, 89 type
2B, and 17 type 3 tibial defects; and 3 type 2A, 34 type 2B, and 4 type 3 femoral
defects. There were 3 intraoperative fractures (1.9%) associated with sleeve
preparation and/or insertion. Six knees (5 patients) were lost to follow-up and 5
patients (6 knees) died before 2 years. Of the remaining 104 knees (98 patients,
134 sleeves), mean follow-up was 5.3 years (range 2-9.6 years). Nineteen knees
(16.4%) required reoperation, most commonly for recurrent infection. Only one
sleeve demonstrated radiographic evidence of failed osteointegration, but did not
require revision. Two sleeves (1.5%) required removal and/or resection for
recurrent infection. CONCLUSION: This large retrospective series illustrates the
utility of porous metaphyseal sleeves in revision TKA with a low rate of
intraoperative complications, excellent osteointegration, and long-term fixation.
PMID- 28697865
TI - Revision Total Hip Arthroplasty Using a Cementless Cup Supporter and Iliac
Autograft: A Minimum of 15-Year Follow-Up.
AB - BACKGROUND: Bone deficiency in revision total hip arthroplasty is a surgical
challenge. The Murata-Chiba cup supporter (MC support ring) is an acetabular
component supporter for a cementless porous-coated cup. The purpose of this study
is to examine the clinical and radiographic outcomes of reconstruction of
acetabular bone deficiency using iliac autografts supported by an MC support ring
in a revision setting with minimum 15-year follow-up. METHODS: Fifty-nine
consecutive revision total hip arthroplasties (57 patients) using the MC support
ring were followed for a minimum of 15 years. Nine hips had American Academy of
Orthopaedic Surgeons type II deficiency and 24 had type III defects of the
acetabulum. Clinical outcomes were evaluated using the Harris hip score.
Radiographic evaluation included assessment for loosening and bone graft
incorporation. Kaplan-Meier survival analysis was performed. RESULTS: At a
minimum 15-year follow-up (mean, 17.6 years), 32 patients (33 hips) were alive,
17 patients (18 hips) were deceased, and 8 patients (8 hips) were lost to follow
up. The mean Harris hip score improved from 44.3 to 77.2 at final follow-up. Four
hips required reoperation due to deep infection (2 hips) and liner dissociation
(2 hips), but no acetabular components were revised for aseptic loosening.
Incorporation of the bone graft occurred in all cases. One unrevised patient had
radiographic failure. Survivorship at 15 years with re-revision or radiographic
failure as the end point was 90.6% (95% confidence interval, 83.0%-98.8%).
CONCLUSION: The reconstruction of acetabular bone deficiency using autografts
supported by an MC support ring provided satisfactory clinical and radiological
results at 17.6 years postoperatively.
PMID- 28697866
TI - Quality Initiative Programs Can Decrease Total Joint Arthroplasty Transfusion
Rates-A Multicenter Study Using the MARCQI Total Joint Registry Database.
AB - BACKGROUND: The Michigan Arthroplasty Registry Collaborative Quality Initiative
(MARCQI) noted wide variability between member hospitals in blood transfusion
rates after primary total hip and knee arthroplasty (THA and TKA). Blood
transfusion has substantial risks and accepted recommendations exist to guide
transfusion practices. MARCQI began an initiative to decrease unnecessary
transfusions by identifying/reporting outliers, discussing conservative
transfusion practices, and recommending transfusion guidelines. There was a later
recommendation to consider intraoperative use of tranexamic acid. METHODS: All
MARCQI-registered unilateral TKA and THA cases from the 28 member hospitals (pre
November 2013) were included. For 3 time periods (before November 13, 2013;
November 13, 2013, to November 12, 2014; and after November 12, 2014), we
calculated average risk and range of transfusion, transfusion with nadir
hemoglobin >8 g/dL, mean length of stay, and 90-day risk of discharge to nursing
home, readmission, deep infection, and emergency department visits. RESULTS: For
THA, risk and range of transfusion decreased over the 3 time periods: 12.6% (2.5%
36.2%), 7.6% (2.2%-23.8%), and 4.5% (0.7%-14.4%); for TKA, 6.3% (1.3%-15.6%),
3.1% (0%-12.5%), and 1.3% (0%-7.4%). Decreases were also noted for transfusion
with a nadir hemoglobin >8 g/dL with a near elimination of "unnecessary"
transfusions. There was no evidence of increase in length of stay, discharge to
nursing home, readmission, deep infection, or emergency department visits.
CONCLUSION: A simple intervention can decrease unnecessary blood transfusions
during and after elective primary unilateral THA or TKA. A collaborative registry
can be used effectively to improve the quality of patient care and set a new
benchmark for transfusion.
PMID- 28697867
TI - Authors' reply to the Drs. Finsterer and Zarrouk-Mahjoub's comments for our case
report.
PMID- 28697868
TI - Combination toceranib and lomustine shows frequent high grade toxicities when
used for treatment of non-resectable or recurrent mast cell tumours in dogs: A
European multicentre study.
AB - Mast cell tumours (MCTs) in dogs can present in a variety of forms. Non
resectable, recurrent or metastatic MCTs usually carry a poor prognosis and
present a therapeutic challenge. Both toceranib and lomustine have shown single
agent activity against MCTs in dogs. In this study, 10 dogs with advanced MCTs
were enrolled prospectively and treated with toceranib (median dose 2.7mg/kg
orally every other day), lomustine (median dose 60mg/m2 orally every 3 weeks) and
prednisolone (1mg/kg orally every other day, alternating with toceranib). Severe
adverse events (SAEs), requiring alterations in the protocol, occurred in all
dogs. The objective response rate was 50%. Three dogs died or were euthanased due
to SAEs and therefore enrolment of new dogs was discontinued prematurely. A long
term response (>1year) was observed in two dogs. Modifications of the protocol
are required for future prospective studies.
PMID- 28697869
TI - Perioperative mortality in cats and dogs undergoing spay or castration at a high
volume clinic.
AB - High volume spay-neuter (spay-castration) clinics have been established to
improve population control of cats and dogs to reduce the number of animals
admitted to and euthanazed in animal shelters. The rise in the number of spay
neuter clinics in the USA has been accompanied by concern about the quality of
animal care provided in high volume facilities, which focus on minimally
invasive, time saving techniques, high throughput and simultaneous management of
multiple animals under various stages of anesthesia. The aim of this study was to
determine perioperative mortality for cats and dogs in a high volume spay-neuter
clinic in the USA. Electronic medical records and a written mortality log were
used to collect data for 71,557 cats and 42,349 dogs undergoing spay-neuter
surgery from 2010 to 2016 at a single high volume clinic in Florida.
Perioperative mortality was defined as deaths occurring in the 24h period
starting with the administration of the first sedation or anesthetic drugs.
Perioperative mortality was reported for 34 cats and four dogs for an overall
mortality of 3.3 animals/10,000 surgeries (0.03%). The risk of mortality was more
than twice as high for females (0.05%) as for males (0.02%) (P=0.008) and five
times as high for cats (0.05%) as for dogs (0.009%) (P=0.0007). High volume spay
neuter surgery was associated with a lower mortality rate than that previously
reported in low volume clinics, approaching that achieved in human surgery. This
is likely to be due to the young, healthy population of dogs and cats, and the
continuous refinement of techniques based on experience and the skills and
proficiency of teams that specialize in a limited spectrum of procedures.
PMID- 28697870
TI - Bovine respiratory disease in pre-weaned dairy calves: Are current preventative
strategies good enough?
PMID- 28697871
TI - Patterns of antimicrobial agent prescription in a sentinel population of canine
and feline veterinary practices in the United Kingdom.
AB - Antimicrobial resistance is an increasingly important global health threat and
the use of antimicrobial agents is a key risk factor in its development. This
study describes antimicrobial agent prescription (AAP) patterns over a 2year
period using electronic health records (EHRs) from booked consultations in a
network of 457 sentinel veterinary premises in the United Kingdom. A semi
automated classification methodology was used to map practitioner defined product
codes in 918,333 EHRs from 413,870 dogs and 352,730 EHRs from 200,541 cats,
including 289,789 AAPs. AAP as a proportion of total booked consultations was
more frequent in dogs (18.8%, 95% confidence interval, CI, 18.2-19.4) than cats
(17.5%, 95% CI 16.9-18.1). Prescription of topical antimicrobial agents was more
frequent in dogs (7.4%, 95% CI 7.2-7.7) than cats (3.2%, 95% CI 3.1-3.3), whilst
prescription of systemic antimicrobial agents was more frequent in cats (14.8%,
95% CI 14.2-15.4) than dogs (12.2%, 95% CI 11.7-12.7). A decreasing temporal
pattern was identified for prescription of systemic antimicrobial agents in dogs
and cats. Premises which prescribed antimicrobial agents frequently for dogs also
prescribed frequently for cats. AAP was most frequent during pruritus
consultations in dogs and trauma consultations in cats. Clavulanic acid
potentiated amoxicillin was the most frequently prescribed antimicrobial agent in
dogs (28.6% of prescriptions, 95% CI 27.4-29.8), whereas cefovecin, a third
generation cephalosporin, was the most frequently prescribed antimicrobial agent
in cats (36.2%, 95% CI 33.9-38.5). This study demonstrated patterns in AAP over
time and for different conditions in a population of companion animals in the
United Kingdom.
PMID- 28697872
TI - Life course analysis of the impact of mammary cancer and pyometra on age-anchored
life expectancy in female Rottweilers: Implications for envisioning ovary
conservation as a strategy to promote healthy longevity in pet dogs.
AB - Mammary cancer and pyometra are important health hazards associated with ovary
conservation in pet dogs. Early ovariohysterectomy may reduce the incidence of
these two diseases, but an estimate of the extent to which the development of
mammary cancer or pyometra adversely influences overall longevity is missing. As
a first step toward addressing this knowledge gap, the results of a historical
cohort study of Rottweilers that lived in North America are reported.
Questionnaires completed by owners and veterinarians were used to obtain lifetime
health and medical information on 242 female Rottweilers, including years of
lifetime ovary exposure, age at death, and cause of death. To determine the
extent to which longevity was shortened in females that developed these ovary
associated diseases, age-anchored life expectancy-defined as the median number of
remaining years until death for females alive at specified ages during the life
course-and years of life lost, a measure of premature mortality, were estimated.
Mammary carcinoma was diagnosed in 19 (7.9%) females; median age at diagnosis was
8.5 years; case fatality was 37%. Pyometra was diagnosed in 16 (6.6%) females;
median age at diagnosis was 5.4 years; case fatality was 7%. Median lifetime
ovary exposure for the study population was 4.3 years. Although risk for
developing both diseases increased with longer ovary exposure, longer ovary
exposure (>=4.3 years) was also associated with an overall longevity advantage-a
33% decrease in mortality, living 17 months longer than females with shorter
ovary exposure (P=0.002). Analysis of age-anchored life expectancy showed that at
no time points during the life course was the current or future diagnosis of
mammary carcinoma or pyometra associated with shortened survival compared to
females who never developed these conditions. This lack of longevity disadvantage
is an expected result for diseases with late-onset, moderate (<50%) case fatality
(mammary carcinoma) or low (<10%) case fatality (pyometra). These findings fail
to support the notion that a strategy, such as elective ovariohysterectomy,
implemented to reduce the incidence of mammary carcinoma and pyometra will
beneficially impact overall longevity. It follows that future efforts to find and
implement effective longevity-promoting interventions should look beyond reducing
the incidence of a particular disease to considering trade-offs.
PMID- 28697873
TI - Toxoplasma gondii seroprevalence and association with equine protozoal
myeloencephalitis: A case-control study of Californian horses.
AB - While toxoplasmosis is not commonly considered a clinical disease of equines,
previous seroprevalence studies have reported differing background rates of
Toxoplasma gondii infection in horses globally. The objective of this study was
to evaluate possible associations between T. gondii seroprevalence and clinical
signs of equine protozoal myeloencephalitis (EPM) in horses. Using a case-control
study design, 720 Californian horses with neurologic signs compatible with EPM
were compared to healthy, non-neurologic horses for the presence of T. gondii
antibodies (using indirect fluorescent antibody tests [IFAT]). Toxoplasma gondii
seroprevalence among cases and controls was determined at standard serum cut
offs: 40, 80, 160, 320, and 640. At a T. gondii titre cut-off of 320, horses with
clinical signs compatible with EPM had 3.55 times the odds of a seropositive test
compared to those without clinical signs (P<0.01) when adjusted for covariates.
When restricted to the autumn season and at the same titre cut-off, an EPM
suspect horse had 6.4 times the odds of testing seropositive to T. gondii,
compared to non-neurologic horses. The association between high T. gondii titres
and clinical signs compatible with EPM is potentially reflective of toxoplasmosis
in equines. Serologic testing of cerebrospinal fluid and isolation of T. gondii
in EPM suspect cases should be considered. Future studies investigating the
relationship between T. gondii and EPM are warranted.
PMID- 28697874
TI - Sole haemorrhages in Danish bull calves: Prevalence and risk factors.
AB - To evaluate the prevalence of sole haemorrhages among Danish dairy breed bull
calves and associated risk factors, 730 calves were hoof trimmed shortly before
slaughter and the presence of sole haemorrhages was recorded. Associations
between the outcomes sole haemorrhages and severe sole haemorrhages, and the
explanatory variables daily weight gain, liver abscesses and flooring, were
analysed. Of the 730 calves, 545 (74.7%) had sole haemorrhages and 119 (16.3%)
had severe sole haemorrhages. Calves housed on slatted concrete floors with
cubicles had higher odds of sole haemorrhages (odds ratio, OR, 2.69, 95%
confidence interval, CI, 1.81-4.00; P<0.001) and severe sole haemorrhages (OR
2.07, 95% CI 1.36-3.14; P<0.001) than calves housed on deep litter straw. The
odds of severe sole haemorrhages increased with increasing daily weight gain (OR
1.28, 95% CI 1.07-1.54 for an increase of 100g/day; P=0.008).
PMID- 28697875
TI - Molecular characteristics of clinical methicillin-resistant Staphylococcus
pseudintermedius harboring arginine catabolic mobile element (ACME) from dogs and
cats.
AB - This study aimed to investigate the presence of arginine catabolic mobile element
(ACME) and its associated molecular characteristics in methicillin-resistant
Staphylococcus pseudintermedius (MRSP). Among the 72 S. pseudintermedius
recovered from various infection sites of dogs and cats, 52 (72.2%) were MRSP.
ACME-arcA was detected commonly (69.2%) in these MRSP isolates, and was more
frequently detected in those from the skin than from other body sites (P=0.047).
There was a wide genetic diversity among the ACME-arcA-positive MRSP isolates,
which comprised three SCCmec types (II-III, III and V) and 15 dru types with two
predominant clusters (9a and 11a). Most MRSP isolates were multidrug-resistant.
Since S. pseudintermedius could serve as a reservoir of ACME, further research on
this putative virulence factor is recommended.
PMID- 28697876
TI - Pharmacokinetics of the anti-androgenic drug flutamide in healthy stallions.
AB - Alternatives to surgical castration are necessary for controlling the sexual
behaviour of stallions with breeding potential in training and competition.
Flutamide is a potent selective non-steroidal androgen receptor competitive
antagonist that has been used in human beings as an anti-androgenic drug. In this
study, the pharmacokinetics and bioavailability of flutamide and its main active
metabolite, 2-hydroflutamide, were determined in seven healthy mature stallions.
Single doses of flutamide (1mg/kg intravenously, 1mg/kg orally in fasted horses,
5mg/kg orally in fasted horses and 5mg/kg orally in fed horses) were administered
randomly at intervals of 2 weeks. All horses had full physical examinations and
blood samples were collected for pharmacokinetics, complete blood counts and
biochemistry before and after drug administration. Administration of flutamide
did not result in any abnormalities on physical examination or in blood
parameters. After intravenous administration of flutamide, the volume of
distribution was 0.83L/kg and clearance was 1.20L/h/kg. Flutamide and its
metabolite had high protein binding values (93-97%). After oral administration,
flutamide was rapidly transformed to 2-hydroxyflutamide, with areas under the
concentration-time curve ratios of metabolite:drug ~7. Oral bioavailability was
6.63% after 1mg/kg flutamide in fasted horses, 6.50% after 5mg/kg flutamide in
fasted horses and 6.95% after 5mg/kg in fed horses. Half lives of flutamide were
close to 1h after intravenous administration and 2h after oral administration.
Half lives of 2-hydroxyflutamide were 4.79-6.84h for all routes and doses. After
oral administration, oral flutamide reached plasma concentrations that could be
effective as an anti-androgenic agent in horses, but further studies are needed
to determine whether flutamide has clinical value as an alternative to castration
for controlling sexual behaviour in stallions.
PMID- 28697877
TI - Alterations in thoracolumbosacral movement when pain causing lameness has been
improved by diagnostic analgesia.
AB - Lameness, thoracolumbosacral pain and reduced range of motion (ROM) often
coexist; better understanding of their relationship is needed. The objectives
were to determine if thoracolumbosacral movement of horses changes when pain
causing lameness is improved by diagnostic analgesia. We hypothesised that
reduction of lameness will increase ROM of the thoracolumbosacral region.
Thirteen horses with different types of hind limb lameness were trotted in
straight lines and lunged on a 10m diameter circle on left and right reins before
and after lameness was subjectively substantially improved by diagnostic
analgesia. Inertial sensor data were collected from the withers, thirteenth (T13)
and eighteenth thoracic (T18) vertebrae, third lumbar (L3) vertebra, tubera
sacrale (TS), left and right tubera coxae. ROM of flexion-extension, axial
rotation, lateral bending, dorsoventral, lateral-lateral motion and vertical
movement symmetry were quantified at each thoracolumbar site. Hiphike difference
(HHD), maximum difference (MaxDiff) and minimum difference (MinDiff) for the
pelvic sensors were measured. Percentage changes for before and after diagnostic
analgesia were calculated; mean+/-standard deviation (SD) or median
[interquartile range] were determined. Associations between the change in pelvic
versus thoracolumbar movement symmetry after each local analgesic technique were
tested. After resolution of lameness, HHD decreased by 7% [68%] (P=0.006). The
MinDiff decreased significantly by 33% [61%] (P=0.01), 45+/-13% (P=0.005) and
52+/-23% (P=0.04), for TS, L3 and T18, respectively. There was significantly
increased ROM in flexion-extension at T13, in axial rotation at T13, T18, L3 and
in lateral-lateral ROM at L3. Thoracolumbosacral asymmetry and reduced ROM
associated with lameness were both altered immediately by improvement in lameness
using diagnostic analgesia.
PMID- 28697878
TI - Current insights into the molecular genetic basis of dwarfism in livestock.
AB - Impairment of bone growth at a young age leads to dwarfism in adulthood. Dwarfism
can be categorised as either proportionate, an overall size reduction without
changes in body proportions, or disproportionate, a size reduction in one or more
limbs, with changes in body proportions. Many forms of dwarfism are inherited and
result from structural disruptions or disrupted signalling pathways. Hormonal
disruptions are evident in Brooksville miniature Brahman cattle and Z-linked
dwarfism in chickens, caused by mutations in GH1 and GHR. Furthermore, mutations
in IHH are the underlying cause of creeper achondroplasia in chickens. Belgian
blue cattle display proportionate dwarfism caused by a mutation in RNF11, while
American Angus cattle dwarfism is caused by a mutation in PRKG2. Mutations in
EVC2 are associated with dwarfism in Japanese brown cattle and Tyrolean grey
cattle. Fleckvieh dwarfism is caused by mutations in the GON4L gene. Mutations in
COL10A1 and COL2A1 cause dwarfism in pigs and Holstein cattle, both associated
with structural disruptions, while several mutations in ACAN are associated with
bulldog-type dwarfism in Dexter cattle and dwarfism in American miniature horses.
In other equine breeds, such as Shetland ponies and Friesian horses, dwarfism is
caused by mutations in SHOX and B4GALT7. In Texel sheep, chondrodysplasia is
associated with a deletion in SLC13A1. This review discusses genes known to be
involved in these and other forms of dwarfism in livestock.
PMID- 28697879
TI - Evaluation of three hand-held tonometers in normal canine eyes.
AB - Tonometry, an indirect measurement of intraocular pressure (IOP), is important
for the diagnosis and management of glaucoma and uveitis. The aim of this study
was to compare the performance of three hand-held tonometers in normal canine
eyes. Eyes from cadavers of dogs without observable ocular disease were used to
compare tonometric measurements with direct manometry over a range of 7.4-65mmHg.
In vivo measurements using the three tonometers in both eyes of 12 healthy dogs
were compared. All tonometers significantly underestimated manometric values both
ex vivo and in vivo. One tonometer showed a small fixed bias over the range of
IOP, whilst the other two tonometers had a negative proportional bias. The
results of this study show that differences exist between handheld tonometers
across the clinically relevant range of IOP, and that all underestimate
manometric measurements.
PMID- 28697880
TI - Comparison of autologous bone marrow and adipose tissue derived mesenchymal stem
cells, and platelet rich plasma, for treating surgically induced lesions of the
equine superficial digital flexor tendon.
AB - Several therapies have been investigated for equine tendinopathies, but
satisfactory long term results have not been achieved consistently and a better
understanding of the healing mechanism elicited by regenerative therapies is
needed. The aim of this study was to assess the separate effects of autologous
bone marrow (BM) and adipose tissue (AT) derived mesenchymal stem cells (MSCs),
and platelet rich plasma (PRP), for treating lesions induced in the superficial
digital flexor tendon (SDFT) of horses. Lesions were created surgically in both
SDFTs of the forelimbs of 12 horses and were treated with BM-MSCs (six tendons),
AT-MSCs (six tendons) or PRP (six tendons). The remaining six tendons received
lactated Ringer's solution as control. Serial ultrasound assessment was performed
prior to treatment and at 2, 6, 10, 20 and 45 weeks post-treatment. At 45 weeks,
histopathology and gene expression analyses were performed. At week 6, the
ultrasound echogenicity score in tendons treated with BM-MSCs suggested earlier
improvement, whilst all treatment groups reached the same level at week 10, which
was superior to the control group. Collagen orientation scores on histological
examination suggested a better outcome in treated tendons. Gene expression was
indicative of better tissue regeneration after all treatments, especially for BM
MSCs, as suggested by upregulation of collagen type I, decorin, tenascin and
matrix metalloproteinase III mRNA. Considering all findings, a clear beneficial
effect was elicited by all treatments compared with the control group. Although
differences between treatments were relatively small, BM-MSCs resulted in a
better outcome than PRP and AT-MSCs.
PMID- 28697881
TI - Incarceration of the Posterior Tibial Tendon in an Isolated Comminuted Medial
Malleolus Fracture.
AB - Isolated medial malleolar fractures are a less common presentation of an ankle
fracture. Treatment is not universally accepted, although many have agreed that
any displacement warrants anatomic reduction and fixation. We present a case of
an isolated, comminuted medial malleolar fracture that was displaced secondary to
entrapment of the posterior tibial tendon between the fracture fragments
requiring surgical intervention. The patient was treated with prompt open
reduction and internal fixation and had an excellent functional outcome at 1
year. When open reduction and internal fixation of the medial malleolus is
indicated, a thorough exploration of the zone of injury is required to identify
and adequately address any surrounding pathologic features beyond just the
disrupted bony anatomy. To the best of our knowledge, this specific injury has
never been previously reported and emphasizes the importance of understanding the
local anatomy and how restoration of the distorted anatomy is vital to optimize
patient function.
PMID- 28697882
TI - The emotional and professional wellbeing of Australian midwives: A comparison
between those providing continuity of midwifery care and those not providing
continuity.
AB - BACKGROUND: Continuity of midwifery care contributes to significant positive
outcomes for women and babies. There is a perception that providing continuity of
care may negatively impact on the wellbeing and professional lives of midwives.
AIM: To compare the emotional and professional wellbeing as well as satisfaction
with time off and work-life balance of midwives providing continuity of care with
midwives not providing continuity. METHOD: Online survey. Measures included;
Copenhagen Burnout Inventory (CBI); Depression, Anxiety and Stress Scale-21; and
Perceptions of Empowerment in Midwifery Scale (PEMS-Revised). The sample (n=862)
was divided into two groups; midwives working in continuity (n=214) and those not
working in continuity (n=648). Mann Whitney U tests were used to compare the
groups. RESULTS: The continuity group had significantly lower scores on each of
the burnout subscales (CBI Personal p=.002; CBI Work p<.001; CBI Client p<.001)
and Anxiety (p=.007) and Depression (p=.004) sub-scales. Midwives providing
continuity reported significantly higher scores on the PEMs Autonomy/Empowerment
subscale (p<.001) and the Skills and Resources subscale (p=.002). There was no
difference between the groups in terms of satisfaction with time off and work
life balance. CONCLUSION: Our results indicate that providing continuity of
midwifery care is also beneficial for midwives. Conversely, midwives working in
shift-based models providing fragmented care are at greater risk of psychological
distress. Maternity service managers should feel confident that re-orientating
care to align with the evidence is likely to improve workforce wellbeing and is a
sustainable way forward.
PMID- 28697883
TI - Effectiveness of local therapy for stage I non-small-cell lung cancer in
nonagenarians.
AB - BACKGROUND: Stage I non-small-cell lung cancer is potentially curable, yet older
patients undergo treatment at lower rates than younger patients. This analysis
sought to describe the treatment outcomes of nonagenarians with stage I non-small
cell lung cancer to better guide treatment decisions in this population. METHODS:
The National Cancer DataBase was queried for patients age >=90 years old with
stage I non-small-cell lung cancer (tumors <=4 cm). Patients were divided into 3
groups: local therapy, other therapy, or no treatment. The primary outcomes were
5-year overall and relative survival. RESULTS: Of the 616 patients identified,
33% (202) were treated with local therapy, 34% (207) were treated with other
therapy, and 34% (207) underwent no treatment. Compared with local therapy,
overall mortality was significantly higher with no treatment (hazard ratio 2.50,
95% confidence interval, 1.95-3.21) and other therapy (hazard ratio 1.43, 95%
confidence interval, 1.11-1.83). The 5-year relative survival was 81% for local
therapy, 49% for other therapy, and 32% for no treatment (P < .0001). CONCLUSION:
Nonagenarians managed with local therapy for stage I non-small-cell lung cancer
(tumors <=4 cm) have better overall survival than those receiving other therapy
or no treatment and should be considered for treatment with either operation or
stereotactic body radiation therapy if able to tolerate treatment.
PMID- 28697884
TI - Transparency and Control of Autonomous Wildness: A Reply to Galaz and Mouazen.
PMID- 28697885
TI - Neutralizing the Threat: Pan-Ebolavirus Antibodies Close the Loop.
AB - The glycoprotein (GP) of ebolaviruses participates in a critical membrane fusion
process to establish infection of a cell and therefore, represents an important
target of both vaccines and antivirals. The latest reports on pan-ebolavirus
monoclonal antibodies in small animal models may offer promising outcomes and
insight into how best to target the GP in vaccine and antiviral discovery.
PMID- 28697886
TI - Revisiting the Structure of Hemoglobin and Myoglobin with Cryo-Electron
Microscopy.
AB - Sixty years ago, the first protein structure of myoglobin was determined by John
Kendrew and his colleagues; hemoglobin followed shortly thereafter. For quite
some time, it seemed that only X-ray crystallography would be capable of
determining the structure of proteins to high resolution. In recent years, cryo
electron microscopy has emerged as a viable alternative and indeed in many cases
the preferred approach. It is capable of studying proteins that span a size range
from several megadaltons to proteins as small as myoglobin and hemoglobin.
PMID- 28697887
TI - Molecular Origins of the Compatibility between Glycosaminoglycans and Abeta40
Amyloid Fibrils.
AB - The Abeta peptide forms extracellular plaques associated with Alzheimer's
disease. In addition to protein fibrils, amyloid plaques also contain non
proteinaceous components, including glycosaminoglycans (GAGs). We have shown
previously that the GAG low-molecular-weight heparin (LMWH) binds to Abeta40
fibrils with a three-fold-symmetric (3Q) morphology with higher affinity than
Abeta40 fibrils in alternative structures, Abeta42 fibrils, or amyloid fibrils
formed from other sequences. Solid-state NMR analysis of the GAG-3Q fibril
complex revealed an interaction site at the corners of the 3Q fibril structure,
but the origin of the binding specificity remained obscure. Here, using a library
of short heparin polysaccharides modified at specific sites, we show that the N
sulfate or 6-O-sulfate of glucosamine, but not the 2-O-sulfate of iduronate
within heparin is required for 3Q binding, indicating selectivity in the
interactions of the GAG with the fibril that extends beyond general electrostatic
complementarity. By creating 3Q fibrils containing point substitutions in the
amino acid sequence, we also show that charged residues at the fibril three-fold
apices provide the majority of the binding free energy, while charged residues
elsewhere are less critical for binding. The results indicate, therefore, that
LMWH binding to 3Q fibrils requires a precise molecular complementarity of the
sulfate moieties on the GAG and charged residues displayed on the fibril surface.
Differences in GAG binding to fibrils with distinct sequence and/or structure may
thus contribute to the diverse etiology and progression of amyloid diseases.
PMID- 28697888
TI - Regulated Expansion and Survival of Chimeric Antigen Receptor-Modified T Cells
Using Small Molecule-Dependent Inducible MyD88/CD40.
AB - Anti-tumor efficacy of T cells engineered to express chimeric antigen receptors
(CARs) is dependent on their specificity, survival, and in vivo expansion
following adoptive transfer. Toll-like receptor (TLR) and CD40 signaling in T
cells can improve persistence and drive proliferation of antigen-specific CD4+
and CD8+ T cells following pathogen challenge or in graft-versus-host disease
(GvHD) settings, suggesting that these costimulatory pathways may be co-opted to
improve CAR-T cell persistence and function. Here, we present a novel strategy to
activate TLR and CD40 signaling in human T cells using inducible MyD88/CD40
(iMC), which can be triggered in vivo via the synthetic dimerizing ligand,
rimiducid, to provide potent costimulation to CAR-modified T cells. Importantly,
the concurrent activation of iMC (with rimiducid) and CAR (by antigen
recognition) is required for interleukin (IL)-2 production and robust CAR-T cell
expansion and may provide a user-controlled mechanism to amplify CAR-T cell
levels in vivo and augment anti-tumor efficacy.
PMID- 28697890
TI - Stress-Induced Neuronal Colony Stimulating Factor 1 Provokes Microglia-Mediated
Neuronal Remodeling and Depressive-like Behavior.
AB - BACKGROUND: Chronic stress exposure causes neuronal atrophy and synaptic deficits
in the medial prefrontal cortex (PFC), contributing to development of anxiety-
and depressive-like behaviors. Concomitantly, microglia in the PFC undergo
morphological and functional changes following stress exposure, suggesting that
microglia contribute to synaptic deficits underlying behavioral consequences.
METHODS: Male and female mice were exposed to chronic unpredictable stress (CUS)
to examine the role of neuron-microglia interactions in the medial PFC during
development of anxiety- and depressive-like behaviors. Thy1-GFP-M mice were used
to assess microglia-mediated neuronal remodeling and dendritic spine density in
the medial PFC. Viral-mediated knockdown of neuronal colony stimulating factor 1
(CSF1) was used to modulate microglia function and behavioral consequences after
CUS. RESULTS: CUS promoted anxiety- and depressive-like behaviors that were
associated with increased messenger RNA levels of CSF1 in the PFC. Increased CSF1
messenger RNA levels were also detected in the postmortem dorsolateral PFC of
individuals with depression. Moreover, microglia isolated from the frontal cortex
of mice exposed to CUS show elevated CSF1 receptor expression and increased
phagocytosis of neuronal elements. Notably, functional alterations in microglia
were more pronounced in male mice compared with female mice. These functional
changes in microglia corresponded with reduced dendritic spine density on
pyramidal neurons in layer 1 of the medial PFC. Viral-mediated knockdown of
neuronal CSF1 in the medial PFC attenuated microglia-mediated neuronal remodeling
and prevented behavioral deficits caused by CUS. CONCLUSIONS: These findings
revealed that stress-induced elevations in neuronal CSF1 provokes microglia
mediated neuronal remodeling in the medial PFC, contributing to synaptic deficits
and development of anxiety- and depressive-like behavior.
PMID- 28697891
TI - Delayed tension pneumoperitoneum after colonoscopy.
PMID- 28697889
TI - Somatostatin-Positive Gamma-Aminobutyric Acid Interneuron Deficits in Depression:
Cortical Microcircuit and Therapeutic Perspectives.
AB - The functional integration of external and internal signals forms the basis of
information processing and is essential for higher cognitive functions. This
occurs in finely tuned cortical microcircuits whose functions are balanced at the
cellular level by excitatory glutamatergic pyramidal neurons and inhibitory gamma
aminobutyric acidergic (GABAergic) interneurons. The balance of excitation and
inhibition, from cellular processes to neural network activity, is
characteristically disrupted in multiple neuropsychiatric disorders, including
major depressive disorder (MDD), bipolar disorder, anxiety disorders, and
schizophrenia. Specifically, nearly 3 decades of research demonstrate a role for
reduced inhibitory GABA level and function across disorders. In MDD, recent
evidence from human postmortem and animal studies suggests a selective
vulnerability of GABAergic interneurons that coexpress the neuropeptide
somatostatin (SST). Advances in cell type-specific molecular genetics have now
helped to elucidate several important roles for SST interneurons in cortical
processing (regulation of pyramidal cell excitatory input) and behavioral control
(mood and cognition). Here, we review evidence for altered inhibitory function
arising from GABAergic deficits across disorders and specifically in MDD. We then
focus on properties of the cortical microcircuit, where SST-positive GABAergic
interneuron deficits may disrupt functioning in several ways. Finally, we discuss
the putative origins of SST cell deficits, as informed by recent research, and
implications for therapeutic approaches. We conclude that deficits in SST
interneurons represent a contributing cellular pathology and therefore a
promising target for normalizing altered inhibitory function in MDD and other
disorders with reduced SST cell and GABA functions.
PMID- 28697892
TI - WITHDRAWN: Bronchopleural fistula after pneumonectomy: Risk factors and
management, focusing on open window thoracostomy.
AB - This article has been withdrawn at the request of the author(s) and/or editor.
The Publisher apologizes for any inconvenience this may cause. The full Elsevier
Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our
business/policies/article-withdrawal.
PMID- 28697893
TI - Mechanical valves in the pulmonary position: An international retrospective
analysis.
AB - OBJECTIVE: Life expectancy of patients with congenital heart disease has improved
over the past decades, increasing the need for a durable pulmonary prosthetic
valve. Biological valves in various forms have become the valve of choice for
pulmonary valve replacement (PVR), but structural valve deterioration is
unavoidable in the long term. Use of a mechanical valve could be an alternative,
but data on long-term outcomes are sparse. METHODS: We retrospectively collected
and analyzed data on 364 patients with mechanical valves implanted in the
pulmonary position between 1965 and 2014. The data originate from medical centers
in Barcelona (Spain), Graz (Austria), Groningen (the Netherlands), Munich
(Germany), Rochester (United States), Seoul (Republic of Korea), and Tehran
(Iran). RESULTS: Median follow-up duration was 4.26 years (range, 0-27 years),
mean age at implantation was 27.16 +/- 12.2 years. Tetralogy of Fallot was the
most common primary cardiac diagnosis, with a subgroup of 69.8%. Freedom from
valvular thrombosis was 91% (95% confidence interval [CI], 87%-94%) at 5 years
and 86% (95% CI, 81%-91%) at 10 years post-PVR. With a success rate up to 88%,
thrombolysis was a successful therapy. Freedom from reoperation was 97% (95% CI,
94%-99%) at 5 years post-PVR and 91% (95% CI, 85%-95%) at 10 years. CONCLUSIONS:
Mechanical PVR is associated with a limited risk of valvular thrombosis.
Thrombolysis was an effective treatment in the majority.
PMID- 28697894
TI - Underestimation of the incidence of new-onset post-coronary artery bypass
grafting atrial fibrillation and its impact on 30-day mortality.
AB - OBJECTIVE: Inconsistent definitions of atrial fibrillation after coronary artery
bypass grafting have caused uncertainty about its incidence and risk. We examined
the extent to which limiting the definition to post-coronary artery bypass
grafting atrial fibrillation events requiring treatment underestimates its
incidence and impact on 30-day mortality. METHODS: We assessed in-hospital atrial
fibrillation and 30-day mortality in 9268 consecutive patients without
preoperative atrial fibrillation who underwent isolated coronary artery bypass
grafting at 5 US hospitals (2004-2010). Patients who experienced 1 or more
episode of post-coronary artery bypass grafting atrial fibrillation detected via
continuous in-hospital electrocardiogram/telemetry monitoring were divided into
those for whom Society of Thoracic Surgeons data (applying the definition "atrial
fibrillation/flutter requiring treatment") also indicated atrial fibrillation
versus those for whom it did not. Risk-adjusted 30-day mortality was compared
between these 2 groups and with patients without post-coronary artery bypass
grafting atrial fibrillation. RESULTS: Risk-adjusted incidence of post-coronary
artery bypass grafting atrial fibrillation incidence was 33.4% (27.0% recorded in
Society of Thoracic Surgeons data, 6.4% missed). Patients with post-coronary
artery bypass grafting atrial fibrillation missed by Society of Thoracic Surgeons
data had a significantly greater risk of 30-day mortality (odds ratio, 2.08, 95%
confidence interval, 1.17-3.69) than those captured. By applying the significant
underestimation of post-coronary artery bypass grafting atrial fibrillation
incidence we observed (odds ratio [Society of Thoracic Surgeons vs missed], 0.78;
95% confidence interval, 0.72-0.83) to the approximately 150,000 patients
undergoing isolated coronary artery bypass grafting in the United States each
year estimates this increased risk of mortality is carried by 9600 patients (95%
confidence interval, 9420-9780) annually. CONCLUSIONS: Defining post-coronary
artery bypass grafting atrial fibrillation as episodes requiring treatment
significantly underestimates incidence and misses patients at a significantly
increased risk for mortality. Further research is needed to determine whether
this increased risk carries over into long-term outcomes and whether it is
mediated by differences in treatment and management.
PMID- 28697895
TI - A neonatal rat model of increased right ventricular afterload by pulmonary artery
banding.
AB - OBJECTIVE: To construct a neonatal rat model of increased right ventricular (RV)
afterload for studying the pathophysiological remodeling of the right ventricle
in patients with congenital heart disease with increased RV afterload. METHODS:
Surgery was performed within 6 hours after birth. Horizontal thoracotomy was
performed by dissecting the intercostal muscles and splitting the sternum. The PA
was then banded with 11-0 nylon thread. At postnatal day 7 (P7), constriction of
PA was confirmed by echocardiography. The RV systolic and diastolic pressures
were measured by cardiac catheterization. The RV end-systolic volume, end
diastolic volume, end-diastolic diameter, and free wall thickness were assessed
by magnetic resonance imaging. The histological changes in sham-operated and PA
banding (PAB) hearts were evaluated by hematoxylin and eosin staining. RESULTS:
Increased RV afterload was established by constriction of the PA in neonatal rats
within 6 hours after birth. The survival rate was 75% at P7. Relative to the sham
group, the peak pressure gradient across the PA constriction and RV systolic and
diastolic pressures, end-systolic volume, end-diastolic volume, end-diastolic
diameter, and free wall thickness were significantly increased in the PAB group
at P7 (P < .01). Consistently, histological examination showed that the RV free
wall was significantly hypertrophic in the PAB group. CONCLUSIONS: We
successfully established a neonatal RV afterload increase model through PAB
within 6 hours after birth, which can be used to study the pathophysiological
changes in congenital heart diseases with increased RV afterload.
PMID- 28697896
TI - Binding Kinetics and Lateral Mobility of HSV-1 on End-Grafted Sulfated
Glycosaminoglycans.
AB - Many viruses, including herpes simplex (HSV), are recruited to their host cells
via interaction between their envelope glycoproteins and cell-surface
glycosaminoglycans (GAGs). This initial attachment is of a multivalent nature,
i.e., it requires the establishment of multiple bonds between amino acids of
viral glycoproteins and sulfated saccharides on the GAG chain. To gain
understanding of how this binding process is modulated, we performed binding
kinetics and mobility studies using end-grafted GAG chains that mimic the end
attachment of these chains to proteoglycans. Total internal reflection
fluorescence microscopy was used to probe binding and release, as well as the
diffusion of single HSV-1 particles. To verify the hypothesis that the degree of
sulfation, but also the arrangement of sulfate groups along the GAG chain, plays
a key role in HSV binding, we tested two native GAGs (chondroitin sulfate and
heparan sulfate) and compared our results to chemically sulfated hyaluronan. HSV
1 recognized all sulfated GAGs, but not the nonsulfated hyaluronan, indicating
that binding is specific to the presence of sulfate groups. Furthermore we
observed that a notable fraction of GAG-bound virions exhibit lateral mobility,
although the multivalent binding to the immobilized GAG brushes ensures firm
virus attachment to the interface. Diffusion was faster on the two native GAGs,
one of which, chondroitin sulfate, was also characterized by the highest
association rate per GAG chain. This highlights the complexity of multivalent
virus-GAG interactions and suggests that the spatial arrangement of sulfates
along native GAG chains may play a role in modulating the characteristics of the
HSV-GAG interaction. Altogether, these results, obtained with a minimal and well
controlled model of the cell membrane, provide, to our knowledge, new insights
into the dynamics of the HSV-GAG interaction.
PMID- 28697897
TI - Measuring Protein Binding to Lipid Vesicles by Fluorescence Cross-Correlation
Spectroscopy.
AB - Fluorescence correlation spectroscopy has been previously used to investigate
peptide and protein binding to lipid membranes, as it allows for very low amounts
of sample, short measurement times and equilibrium binding conditions. Labeling
only one of the binding partners, however, comes with certain drawbacks, as it
relies on identifying binding events by a change in diffusion coefficient. Since
peptide and protein aggregation can obscure specific binding, and since non
stoichiometric binding necessitates the explicit choice of a statistical
distribution for the number of bound ligands, we additionally label the liposomes
and perform dual-color fluorescence cross-correlation spectroscopy (dcFCCS). We
develop a theoretical framework showing that dcFCCS amplitudes allow calculation
of the degree of ligand binding and the concentration of unbound ligand, leading
to a model-independent binding curve. As the degree of labeling of the ligands
does not factor into the measured quantities, it is permissible to mix labeled
and unlabeled ligand, thereby extending the range of usable protein
concentrations and accessible dissociation constants, KD. The total protein
concentration, but not the fraction of labeled protein, needs to be known. In
this work, we apply our dcFCCS analysis scheme to Sar1p, a protein of the COPII
complex, which binds "major-minor-mix" liposomes. A Langmuir isotherm model
yields KD=(2.1+/-1.1)MUM as the single-site dissociation constant. The dcFCCS
framework presented here is highly versatile for biophysical analysis of binding
interactions. It may be applied to many types of fluorescently labeled ligands
and small diffusing particles, including nanodiscs and liposomes containing
membrane protein receptors.
PMID- 28697898
TI - Fusion Domains Guide the Oriented Insertion of Light-Driven Proton Pumps into
Liposomes.
AB - One major objective of synthetic biology is the bottom-up assembly of
minimalistic nanocells consisting of lipid or polymer vesicles as architectural
scaffolds and of membrane and soluble proteins as functional elements. However,
there is no reliable method to orient membrane proteins reconstituted into
vesicles. Here, we introduce a simple approach to orient the insertion of the
light-driven proton pump proteorhodopsin (PR) into liposomes. To this end, we
engineered red or green fluorescent proteins to the N- or C-terminus of PR,
respectively. The fluorescent proteins optically identified the PR constructs and
guided the insertion of PR into liposomes with the unoccupied terminal end facing
inward. Using the PR constructs, we generated proton gradients across the vesicle
membrane along predefined directions such as are required to power (bio)chemical
processes in nanocells. Our approach may be adapted to direct the insertion of
other membrane proteins into vesicles.
PMID- 28697899
TI - HIV and coronary disease - When secondary prevention is insufficient.
AB - Highly active antiretroviral therapy (HAART) has created a new paradigm for human
immunodeficiency virus (HIV)-infected patients, but their increased risk for
coronary disease is well documented. We present the case of a 57-year-old man, co
infected with HIV-2 and hepatitis B virus, adequately controlled and with insulin
treated type 2 diabetes and dyslipidemia, who was admitted with non-ST elevation
acute myocardial infarction. Coronary angiography performed on day four of
hospital stay documented two-vessel disease (mid segment of the right coronary
artery [RCA, 90% stenosis] and the first marginal). Two drug-eluting stents were
successfully implanted. The patient was discharged under dual antiplatelet
therapy (aspirin 100 mg/day and clopidogrel 75 mg/day) and standard coronary
artery disease medication. He was admitted to the emergency room four hours after
discharge with chest pain radiating to the left arm and inferior ST-segment
elevation myocardial infarction was diagnosed. Coronary angiography was performed
within one hour and documented thrombosis of both stents. Optical coherence
tomography revealed good apposition of the stent in the RCA, with intrastent
thrombus. Angioplasty was performed, with a good outcome. The acute stent
thrombosis might be explained by the thrombotic potential of HIV infection and
diabetes. There are no specific guidelines regarding HAART in secondary
prevention of acute coronary syndromes. A multidisciplinary approach is essential
for optimal management of these patients.
PMID- 28697900
TI - The distribution of human papillomavirus genotypes in cervical cancer and
intraepithelial neoplasia lesions among Chinese women in Yunnan Province.
AB - This study was designed to explore baseline data about the prevalence and
distribution of human papillomavirus (HPV) genotypes among Chinese women who had
cervical intraepithelial lesions and cervical cancer. A total of 511 patients
were recruited, and biopsy samples were collected from these patients. Polymerase
chain reaction was used to detect HPV-positive samples, and the HPV GenoArray kit
was used for genotyping. A total of 23 genotypes were detected, including 13 that
were high risk-HPV (HR-HPV), 3 that were potential high risk-HPV (PHR-HPV) and 7
that were low risk-HPV (LR-HPV). The prevalence rates of HPV infection in Han
women diagnosed with cervical intraepithelial lesions (CIN) 1, 2, and 3 and
squamous cell carcinoma (SCC) were 98.30%, 97.56, 100% and 90%, respectively. The
HPV-positive cases in women of other ethnicities diagnosed with CIN1, CIN2, and
CIN3 and SCC were 95%, 90.91%, 88.23% and 83.33%, respectively. The most frequent
genotypes in both ethnic groups were HPV-16, 52, and 58. LR-HPV was detected in
SCC lesions in the non-Han ethnic group. In the Han ethnic group, the LR-HPV
genotype was mostly restricted to CIN1 lesions. Furthermore, we found a high
prevalence of PHR-HPV-81 in SCC lesions among Han women. Ethnic background,
smoking, sex at an early age, unprotected sex, use of contraceptives, and the
withdrawal method were found to be significantly associated with HPV infection.
In conclusion, this study explores epidemiological data regarding the prevalence
of HPV and the genotype distribution in patients with SCC and CIN lesions in
Yunnan Province, China.
PMID- 28697901
TI - Knowledge and attitudes towards Zika virus among medical students in King
Abdulaziz University, Jeddah, Saudi Arabia.
AB - Zika Virus (ZIKV) and its associated consequences remain vital public health
challenge of international concerns. The current study was done to assess
knowledge and attitudes towards ZIKV and the factors associated with good
knowledge among medical students in King Abdulaziz University, Jeddah. A cross
sectional study was conducted among 426 students. They were selected through
multistage stratified random sample method, 2016. A validated, confidential,
interviewing questionnaire contained 25 knowledge and 10 attitude items was used.
Descriptive and inferential statistics were done. Results revealed that Facebook
was the commonest source of ZIKV information. About half of the participants
correctly identified mosquito bites and vertical route as ZIKV transmission
modes. However, smaller percentages recognized the sexual and blood transmission
modes. Calculations of knowledge score revealed that 77.5%, 15.0%, and 7.5% of
the participants obtained poor, fair, and satisfactory scores, respectively. Age,
educational year and attending ZIKV training were significantly associated with
good knowledge (p<0.05). Concerning attitudes, about half of the participants
agreed that ZIKV could add new burden on healthcare system of the affected
countries. Most of participants were interested in learning more about ZIKV,
emerging diseases and travel epidemiology. In conclusion, medical students had
limited knowledge about ZIKV, and good attitudes towards learning about it.
Conduction of ZIKV educational programs, and development of courses about
emerging disease epidemiology are required.
PMID- 28697902
TI - Acquired thrombotic thrombocytopenic purpura and pregnancy: More light than shade
but controversies remain.
PMID- 28697903
TI - Implicit self-other discrimination affects the interplay between multisensory
affordances of mental representations of faces.
AB - Face recognition is an apparently straightforward but, in fact, complex ability,
encompassing the activation of at least visual and somatosensory representations.
Understanding how identity shapes the interplay between these face-related
affordances could clarify the mechanisms of self-other discrimination. To this
aim, we exploited the so-called "face inversion effect" (FIE), a specific bias in
the mental rotation of face images (of other people): with respect to inanimate
objects, face images require longer time to be mentally rotated from the upside
down. Via the FIE, which suggests the activation of somatosensory mechanisms, we
assessed identity-related changes in the interplay between visual and
somatosensory affordances between self- and other-face representations.
Methodologically, to avoid the potential interference of the somatosensory
feedback associated with musculoskeletal movements, we introduced the tracking of
gaze direction to record participants' response. Response times from twenty
healthy participants showed the larger FIE for self- than other-faces, suggesting
that the impact of somatosensory affordances on mental representation of faces
varies according to identity. The present study lays the foundations of a
quantifiable method to implicitly assess self-other discrimination, with possible
translational benefits for early diagnosis of face processing disturbances (e.g.
prosopagnosia), and for neurophysiological studies on self-other discrimination
in ethological settings.
PMID- 28697904
TI - The ADRA2B gene in the production of false memories for affective information in
healthy female volunteers.
AB - False memories are common memory distortions in everyday life and seem to
increase with affectively connoted complex information. In line with recent
studies showing a significant interaction between the noradrenergic system and
emotional memory, we investigated whether healthy volunteer carriers of the
deletion variant of the ADRA2B gene that codes for the alpha2b-adrenergic
receptor are more prone to false memories than non-carriers. In this study, we
collected genotype data from 212 healthy female volunteers; 91 ADRA2B carriers
and 121 non-carriers. To assess gene effects on false memories for affective
information, factorial mixed model analysis of variances (ANOVAs) were conducted
with genotype as the between-subjects factor and type of memory error as the
within-subjects factor. We found that although carriers and non-carriers made
comparable numbers of false memory errors, they showed differences in the
direction of valence biases, especially for inferential causal errors.
Specifically, carriers produced fewer causal false memory errors for scripts with
a negative outcome, whereas non-carriers showed a more general emotional effect
and made fewer causal errors with both positive and negative outcomes. These
findings suggest that putatively higher levels of noradrenaline in deletion
carriers may enhance short-term consolidation of negative information and lead to
fewer memory distortions when facing negative events.
PMID- 28697905
TI - Have the principles of experimental medicine become obsolete in the era of big
data?
PMID- 28697906
TI - The Case | A patient with antineutrophil cytoplasmic antibody-positive vasculitis
on treatment with fever and leucopenia.
PMID- 28697907
TI - The contemporary utility of intraoperative frozen sections in thyroid surgery.
AB - PURPOSE: To determine the accuracy of intraoperative frozen section analysis on
thyroidectomy specimens stratified by the Bethesda classification scheme and its
utility for intraoperative decision-making. STUDY DESIGN: Retrospective chart
review. METHODS: A retrospective review was performed on all patients who
underwent thyroidectomy or thyroid lobectomy with intraoperative frozen sections
at a tertiary care academic center from 2009 to 2015. RESULTS: There were 74
total patients who underwent partial or total thyroidectomy with intraoperative
frozen section analysis of a thyroid nodule whom had previously undergone a
thyroid fine needle aspiration of the nodule. The sensitivity, specificity,
positive predictive value, and negative predictive value for a thyroid frozen
section with respect to its prediction for malignancy was 81%, 95%, 98%, and 66%,
respectively, with a diagnostic accuracy of 85%. For 37 patients with an
indeterminate cytologic diagnosis on fine needle aspiration (Bethesda categories
III-V), the sensitivity, specificity, positive predictive value, and negative
predictive value for a thyroid frozen section was 81%, 91%, 95%, and 67%,
respectively, with a diagnostic accuracy of 84%. False positives and false
negatives resulted in 1 completion thyroidectomy for benign pathology and 3
reoperations for malignancy not discovered on frozen section. CONCLUSION: While
intraoperative frozen sections on thyroid specimens may be helpful if positive,
the false negative rate remains high. There appears to be limited value in
routine frozen sections to guide clinical management and decision-making in the
era of the Bethesda system.
PMID- 28697908
TI - Sperm donor conception and disclosure to children: a 10-year retrospective follow
up study of parental attitudes in one French center for the study and
preservation of eggs and sperm (CECOS).
AB - OBJECTIVE: To evaluate the percentage of parents in one French center for the
study and preservation of eggs and sperm who disclose their use of donated
spermatozoa to their children. DESIGN: A questionnaire survey of couples who had
a child using donated spermatozoa. SETTING: University hospital laboratory.
PATIENT(S): One hundred five couples. INTERVENTION(S): Questionnaire sent by
mail. MAIN OUTCOME MEASURE(S): The percentage of parents who disclose their use
of donated spermatozoa to their child. RESULT(S): Among the 157 questionnaires
sent, 105 couples answered, which corresponded to 138 children. There were 40
(38%) couples who had already disclosed the donor origin to their child and 65
(62%) who had not. Of the 40 couples who disclosed the donor origin, 37 (93%) had
intended to do so before making use of assisted reproductive techniques (ART),
but two (5%) had not wanted to do so before ART. Among the 65 couples who did not
inform their child, 42 (65%) planned to inform their child soon, but 20 (31%)
wanted to keep the sperm origin secret. Of the 20 couples who wanted to keep the
origin secret, nine couples had told other persons about the gamete donation but
had not informed their child and do not intend to inform their child in the
future. CONCLUSION(S): This first report about disclosure attitude in a large
cohort of parents of donor-conceived offspring in France showed that most parents
had already disclosed their use of donated spermatozoa to their children or
intended to disclose it soon and had an attitude after birth consistent with
their intentions prior to ART.
PMID- 28697909
TI - Women and the opioid crisis: historical context and public health solutions.
AB - Driven by a legitimate but overly opioid-focused response to pain, the United
States is currently experiencing an opioid crisis, a crisis with parallels to the
first opioid epidemic at the turn of the 20th century. Women, particularly white
reproductive-age women, are increasingly the face of the opioid crisis. Given the
penetration of opioid misuse and addiction across all income and insurance
strata, any provider who cares for women needs to be prepared to assess and
evaluate opioid use, misuse, and addiction. Although responsible opioid
prescribing is essential, treatment capacity must be expanded and be inclusive of
the unique needs of women. However, the public and public health response to the
opioid crisis must include rolling back the war on drugs. The continued
criminalization of the public health issue of drug use and the medical condition
of addiction is unethical, ineffective, and inhumane.
PMID- 28697910
TI - Duphaston and human menopausal gonadotropin protocol in normally ovulatory women
undergoing controlled ovarian hyperstimulation during in vitro
fertilization/intracytoplasmic sperm injection treatments in combination with
embryo cryopreservation.
AB - OBJECTIVE: To evaluate endocrine characteristics and clinical outcomes in normal
ovulatory patients undergoing controlled ovarian hyperstimulation (COH) with the
use of a Duphaston and hMG protocol during in vitro fertilization
(IVF)/intracytoplasmic sperm injection (ICSI) treatments in combination with
frozen-thawed embryo transfer (FET) compared with the characteristics and
outcomes of patients undergoing an Utrogestan and hMG protocol. DESIGN:
Prospective controlled study. SETTING: Tertiary care academic medical center.
PATIENT(S): A total of 250 infertile patients undergoing IVF/ICSI treatments.
INTERVENTION(S): Duphaston (20 mg/d) or Utrogestan (100 mg/d) was taken orally
from cycle day 3 until the trigger day, with hMG (150-225 IU) administered when
appropriate. When the dominant follicles reached maturity, 0.1 mg GnRH agonist
was used as the trigger. Viable embryos were cryopreserved in both protocols for
transfer at a later time. MAIN OUTCOME MEASURE(S): The primary outcome was the
number of oocytes retrieved. Secondary outcomes included the incidence of
premature LH surge, the number of viable embryos, and clinical pregnancy outcomes
from FET cycles. RESULT(S): Consistent LH suppression was achieved during COH.
None of the participants experienced a premature LH surge. The number of oocytes
retrieved (8.22 +/- 5.46 vs. 8.8 +/- 5.62) was similar between the two groups. No
between-group significant differences were observed in the number of mature
oocytes (7.2 +/- 4.72 vs. 6.98 +/- 4.68), fertilized oocytes (6.16 +/- 4.34 vs.
6.32 +/- 4.23), and viable embryos (2.96 +/- 2.22 vs. 3.4 +/- 2.54). Furthermore,
the clinical pregnancy rates (53.04% vs. 51.7%), early miscarriage rates (8.2%
vs. 11.84%), implantation rates (38.68% vs. 35.71%), and cumulative pregnancy
rates per woman (66.67% vs. 69.47%) were also similar. CONCLUSION(S): Duphaston
administration during COH was similar to Utrogestan in the prevention of LH
surge, embryonic characteristics, and pregnancy outcomes. CLINICAL TRIAL
REGISTRATION NUMBER: ChiCTR-IOR-15007265.
PMID- 28697911
TI - Preimplantation genetic screening: what is the clinical efficiency?
PMID- 28697912
TI - Screening, brief intervention, and referral to treatment for opioid and other
substance use during infertility treatment.
AB - Opioid use and misuse have reached epidemic proportions in the United States,
especially in women of childbearing age, some of whom seek infertility
treatments. Substance use is much more common than many of the conditions
routinely screened for during the preconception period, and it can have
devastating consequences for the woman and her family. Substance use can worsen
infertility, complicate pregnancy, increase medical problems, and lead to
psychosocial difficulties for the woman and her family. The reproductive
endocrinologist thus has an ethical and medical duty to screen for substance use,
provide initial counseling, and refer to specialized treatment as needed. This
article provides an overview of screening, brief intervention, and referral to
treatment (SBIRT), a public health approach shown to be effective in ameliorating
the harms of substance use.
PMID- 28697913
TI - Uterine transposition: technique and a case report.
AB - OBJECTIVE: To report the first uterine transposition for fertility preservation
in a patient with rectal cancer. DESIGN: Case report. SETTING: Community
hospital. PATIENT(S): A 26-year-old patient with stage cT3N1M0 rectal
adenocarcinoma located 5 cm from the anal margin. INTERVENTION(S): Laparoscopic
transposition of the uterus to the upper abdomen, outside of the scope of
radiation, was performed to preserve fertility. After the end of radiotherapy,
rectosigmoidectomy was performed and the uterus was repositioned into the pelvis.
MAIN OUTCOME MEASURE(S): Uterine and ovarian function preservation. RESULT(S):
The patient had two menstrual periods and exhibited normal variation in ovarian
hormones throughout the course of neoadjuvant therapy. Menstruation began 2 weeks
after reimplantation into the pelvis, and the cervix exhibited a normal
appearance on clinical examination after 6 weeks. Eighteen months after the
surgery, the uterus was normal and there was no sign of disease. CONCLUSION(S):
Uterine transposition might represent a valid option for fertility preservation
in women who require pelvic radiotherapy and want to bear children. However,
studies that assess its viability, effectiveness, and safety are required.
PMID- 28697914
TI - Introduction: The specter of opiate addiction in reproductive medicine.
AB - The alarming trend in opiate misuse in developed countries is prompting an
increasingly strident public call for action. Although many in our field have
assumed that this building crisis does not really affect us or our patients, data
show that the emerging demographic at highest risk for misusing opiates clearly
includes patients who seek care in our practices. The goals of this Views and
Reviews are to provide a clear understanding of emerging trends in opiate misuse,
to review the impact of opiates on the reproductive axis, and to suggest
practical recommendations aimed at both mitigating iatrogenic influences on
promoting misuse and developing treatment frameworks when misuse is suspected or
identified. Regrettably, there is little if any information on treatment of
opiate misuse in the infertility population; we are perhaps best served by
learning from successful approaches used in pregnant patients. It is hoped that
this Views and Reviews will stimulate focused research and, ultimately, evidence
based guidelines and pathways that will address this widespread clinical problem.
PMID- 28697915
TI - Perioperative pain management strategies among women having reproductive
surgeries.
AB - This review presents opioid-sparing strategies for perioperative pain management
among women undergoing reproductive surgeries and procedures. Recommendations are
provided regarding the use of nonsteroidal anti-inflammatory drugs,
acetaminophen, other adjunctive medications, and regional anesthetic blocks.
Additional considerations for chronic opioid users or patients using opioid
replacement or antagonist therapy are discussed.
PMID- 28697916
TI - Treatments for opioid use disorder among pregnant and reproductive-aged women.
AB - The increased prevalence of opioid use disorder and access to medical insurance
is subsequently increasing the likelihood that medical professionals will
encounter individuals with opioid use disorder. Sharp increases in opioid use
disorder among women mean that obstetricians, gynecologists, and other
reproductive medicine providers may be especially likely to encounter such
patients. Medical professionals' understanding of treatment for opioid use
disorder and their roles in their patients' treatment may increase referrals to
treatment, reduce stigma, and improve the quality of medical care. Treatment for
opioid use disorder falls into four overlapping domains: medication management,
medical care, behavioral/mental health care, and psychosocial support. In this
review, we discuss these domains with an emphasis on pregnant women and women of
reproductive age. Treatment for opioid use disorder is most effective when all
providers coordinate care in an informed, nonjudgmental, patient-centered
approach.
PMID- 28697917
TI - The future of human uterine transplantation: can minimally invasive techniques
provide a uterus suitable for transplant?
PMID- 28697918
TI - Sausage tree (Kigelia africana) flavonoid extract is neuroprotective in AlCl3
induced experimental Alzheimer's disease.
AB - Alzheimer's disease (AD) is a developmental neurodegenerative disorder for which
there is no effective treatment or cure at present. In this study, the
neuroprotective properties of a methanol extract of the leaves of Kigelia
africana (KAE) and its flavonoid-rich fraction (FKAE) in aluminum chloride
(AlCl3)-induced experimental AD was evaluated. Symptoms mimicking AD were induced
in male Sprague Dawley rats by administering 17mg/kg AlCl3, orally, for six
consecutive weeks. Pretreatment of animals with 50 and 100mg/kg KAE or FKAE for
two weeks, followed by their co-administration with AlCl3 for a further four
weeks ameliorated neurological deficits, cerebral oxidative stress, neurochemical
disturbances and histoarchitectural alterations caused by AlCl3 intoxication. The
results suggest that KAE and FKAE are promising therapeutic agents for AD.
PMID- 28697919
TI - Fatty acid translocase promoted hepatitis B virus replication by upregulating the
levels of hepatic cytosolic calcium.
AB - Hepatitis B virus (HBV) is designated a "metabolovirus" due to the intimate
connection between the virus and host metabolism. The nutrition state of the host
plays a relevant role in the severity of HBV infection. Metabolic syndrome (MS)
is prone to increasing HBV DNA loads and accelerating the progression of liver
disease in patients with chronic hepatitis B (CHB). Cluster of differentiation 36
(CD36), also named fatty acid translocase, is known to facilitate long-chain
fatty acid uptake and contribute to the development of MS. We recently found that
CD36 overexpression enhanced HBV replication. In this study, we further explored
the mechanism by which CD36 overexpression promotes HBV replication. Our data
showed that CD36 overexpression increased HBV replication, and CD36 knockdown
inhibited HBV replication. RNA sequencing found some of the differentially
expressed genes were involved in calcium ion homeostasis. CD36 overexpression
elevated the cytosolic calcium level, and CD36 knockdown decreased the cytosolic
calcium level. Calcium chelator BAPTA-AM could override the HBV replication
increased by CD36 overexpression, and the calcium activator thapsigargin could
improve the HBV replication reduced by CD36 knockdown. We further found that CD36
overexpression activated Src kinase, which plays an important role in the
regulation of the store-operated Ca2+ channel. An inhibitor of Src kinase
(SU6656) significantly reduced the CD36-induced HBV replication. We identified a
novel link between CD36 and HBV replication, which is associated with cytosolic
calcium and the Src kinase pathway. CD36 may represent a potential therapeutic
target for the treatment of CHB patients with MS.
PMID- 28697920
TI - Higher plasma corticosterone is associated with reduced costs of infection in red
winged blackbirds.
AB - Glucocorticoid hormones allow individuals to rapidly adjust their physiology and
behavior to meet the challenges of a variable environment. An individual's
baseline concentration of glucocorticoids can reflect shifts in life history
stage and resource demands while mediating a suite of physiological and
behavioral changes that include immune modulation and resource allocation. Thus,
glucocorticoids could facilitate a response to parasites that is optimized for an
individual's specific challenges and life history stage. We investigated the
relationship between endogenous circulating glucocorticoids and measures of
resistance and tolerance to Haemosporidian parasites (including those that cause
avian malaria) in red-winged blackbirds (Agelaius phoeniceus). We found that
higher endogenous concentrations of circulating glucocorticoids were associated
with reduced costs of parasite infection, which is indicative of higher
tolerance, but were unrelated to parasite burden in free ranging, breeding male
birds. Post-breeding, both males and females with higher glucocorticoid
concentrations had higher measures of tolerance to Haemosporidian infection. Our
findings suggest a potentially adaptive role for glucocorticoids in shifting the
response to parasites to align with an individual's current physiological state
and the challenges they face.
PMID- 28697921
TI - New Frameworks for Understanding Sudden Unexpected Deaths in Infancy (SUDI) in
Socially Vulnerable Families.
AB - THEORETICAL PRINCIPLES: Sociological frameworks may enhance understanding of the
complex and multidimensional nature of disadvantage, which is prevalent among
families who experience Sudden Unexpected Death in Infancy (SUDI). PHENOMENA
ADDRESSED: SUDI is the largest category of postneonatal death and largely
associated with the social determinants of health. The highly successful 'Back to
Sleep' campaign has resulted in a more than 85% decrease in SUDI. However, social
inequalities have accompanied this decrease, and the burden of SUDI now lies with
the most disadvantaged and socially vulnerable families. A considerable body of
research on the phenomena of SUDI and disadvantage has been published over the
last decade, demonstrating the widening social gradient in SUDI, and the
importance in recognising structural factors and the multifactorial nature of
disadvantage. Gaps in understanding of risk factors and scepticism about the
received wisdom of health professionals have emerged as central themes in
understanding why socially vulnerable families may adopt unsafe infant care
practices. The direct impact of social disadvantage on infant care has also been
recognised. RESEARCH LINKAGES: The translation of epidemiological findings
regarding SUDI risk into public health recommendations for health professionals
and families alike has to date focused on eliminating individual level risk
behaviours. Unfortunately, such a model largely ignores the broader social,
cultural, and structural contexts in which such behaviours occur. Translating the
new knowledge offered by sociological frameworks and the principles of
behavioural economics into evidence based interventions may assist in the
reduction of SUDI mortality in our most socially vulnerable families.
PMID- 28697922
TI - GL-V9 induced upregulation and mitochondrial localization of NAG-1 associates
with ROS generation and cell death in hepatocellular carcinoma cells.
AB - We have previously reported that a newly synthesized compound, GL-V9 could induce
mitochondria-mediated apoptosis in HepG2 cells. However, the underlying
mechanisms have not been fully understood yet. In current study, we further
showed that GL-V9 exhibited significant inhibitory effect on growth of several
hepatocellular carcinoma cell lines. Moreover, GL-V9-induced growth inhibition
was coincident with the strong upregulation of nonsteroidal anti-inflammatory
drug-activated gene-1 (NAG-1), a TGFbeta superfamily member, which has been
linked with tumor suppression. Further analysis uncovered that GL-V9-activated
p38 MAPK pathway contributed to enhancement of NAG-1 mRNA stability.
Interestingly, we observed that the intracellular NAG-1 protein induced by GL-V9
could, at least in part, localize in mitochondria where it might affect protein
expression, thereby resulting in dissipation of mitochondria membrane potential
(MMP) and accumulation of mitochondrial superoxide, eventually facilitating to
apoptosis events. Silence of NAG-1 could attenuate mitochondria related apoptosis
caused by GL-V9. Moreover, GL-V9 suppressed tumor growth in xenograft model
accompanied with upregulation of NAG-1 in tumor tissues. Collectively, these data
demonstrated that NAG-1 could play an important role in mitochondria apoptosis
triggered by GL-V9, thus providing novel mechanistic explanations and potential
target for using GL-V9 as a chemotherapeutic agent against human hepatocellular
carcinoma.
PMID- 28697923
TI - alpha-Pyrone derivatives with cytotoxic activities, from the endophytic fungus
Phoma sp. YN02-P-3.
AB - Four new alpha-pyrone derivatives phomones C-F (1-4) together with four known
compounds (5-8) were isolated from the endophytic fungus Phoma sp. YN02-P-3.
Compound 1 is the first example of 6-alpha,beta-unsaturated ester-2-pyrone dimers
via intermolecular symmetrical [2+2] cycloaddition. The chemical structures of
these compounds were determined from spectroscopic data (1D/2D NMR, MS and IR).
The acetylated product (9) of 1 along with compounds 1-8 were then tested for
their cytotoxicity against HL-60, PC-3 and HCT-116 cell lines. Compounds 2, 3, 5
and 9 with acetyl groups showed significant inhibitory activities against the
three cell lines with IC50 values in the range 0.52-9.85MUM. while compounds 1, 4
and 6-8 that possess no acetyl group showed no inhibitory activity (IC50>50MUM),
indicating that the acetyl group at 10- or 12- are essential for their cytotoxic
activities. The structure-activity relationships of these phomones were also
reported.
PMID- 28697924
TI - Cranberry products for urinary tract infections.
PMID- 28697925
TI - Variable Expressivity of a Founder Mutation in the EIF2AK4 Gene in Hereditary
Pulmonary Veno-occlusive Disease and Its Impact on Survival.
AB - INTRODUCTION AND OBJECTIVES: Hereditary pulmonary veno-occlusive disease (PVOD)
has been associated with biallelic mutations in EIF2AK4 with the recent discovery
of a founder mutation in Iberian Romani patients with familial PVOD. The aims of
this study were phenotypical characterization and survival analysis of Iberian
Romani patients with familial PVOD carrying the founder p.Pro1115Leu mutation in
EIF2AK4, according to their tolerance to pulmonary vasodilators (PVD). Familial
genetic screening was conducted, as well as assessment of sociocultural
determinants with a potential influence on disease course. METHODS: Observational
study of Romani patients with familial PVOD included in the Spanish Registry of
Pulmonary Arterial Hypertension. Genetic screening of EIF2AK4 was performed in
index cases and relatives between November 2011 and July 2016 and histological
pulmonary examination was carried out in patients who received a lung transplant
or died. The patients were divided into 2 groups depending on their tolerance to
PVD, with comparison of baseline characteristics and survival free of death or
lung transplant. RESULTS: Eighteen Romani patients were included: 9 index cases
and 9 relatives. The biallelic founder mutation in EIF2AK4 was found in all
affected cases and 2 unaffected relatives. Family screening showed 34.2% of
healthy heterozygotes, high consanguinity, young age at childbirth, and frequent
multiparity. Prognosis was bleak, with significant differences depending on
tolerance to PVD. CONCLUSIONS: We describe 2 phenotypes of hereditary PVOD
depending on tolerance to PVD, with prognostic impact and familial distribution.
Consanguinity may have a negative impact on the transmission of PVOD, with
familial genetic screening showing high effectiveness.
PMID- 28697926
TI - Health Literacy and Health Outcomes in Very Old Patients With Heart Failure.
AB - INTRODUCTION AND OBJECTIVES: Health literacy (HL) has been associated with lower
mortality in heart failure (HF). However, the results of previous studies may not
be generalizable because the research was conducted in relatively young and
highly-educated patients in United States settings. This study assessed the
association of HL with disease knowledge, self-care, and all-cause mortality
among very old patients, with a very low educational level. METHODS: This
prospective study was performed in 556 patients (mean age, 85 years), with high
comorbidity, admitted for HF to the geriatric acute-care unit of 6 hospitals in
Spain. About 74% of patients had less than primary education and 71% had
preserved systolic function. Health literacy was assessed with the Short
Assessment of Health Literacy for Spanish-speaking Adults questionnaire,
knowledge of HF with the DeWalt questionnaire, and HF self-care with the European
Heart Failure Self-Care Behaviour Scale. RESULTS: Disease knowledge progressively
increased with HL; compared with being in the lowest (worse) tertile of HL, the
multivariable beta coefficient (95%CI) of the HF knowledge score was 0.60 (0.01
1.19) in the second tertile and 0.87 (0.24-1.50) in the highest tertile, P-trend
= .008. However, no association was found between HL and HF self-care. During the
12 months of follow-up, there were 189 deaths. Compared with being in the lowest
tertile of HL, the multivariable HR (95%CI) of mortality was 0.84 (0.56-1.27) in
the second tertile and 0.99 (0.65-1.51) in the highest tertile, P-trend = .969.
CONCLUSIONS: No association was found between HL and 12-month mortality. This
could be partly due to the lack of a link between HL and self-care.
PMID- 28697927
TI - A Unique Case of Type-1 Facioscapulohumeral Muscular Dystrophy and Sarcomeric
Hypertrophic Cardiomyopathy.
PMID- 28697928
TI - Ivabradine as an Atrioventricular Node Modulator. Promise or Reality? Response.
PMID- 28697929
TI - Impact of large ovarian endometriomas on the response to superovulation for in
vitro fertilization: A retrospective study. Letter to the Editors.
PMID- 28697930
TI - Unicornuate uterus with adenocarcinoma in blind functional contralateral uterine
horn and fallopian tube.
PMID- 28697931
TI - Molecular interaction mechanisms in reverse micellar extraction of microbial
transglutaminase.
AB - Reverse micellar extraction is an efficient and economical alternative for
protein purification. In this study, microbial transglutaminase (MTGase) from
crude materials was purified using reverse micellar extraction, and the molecular
interaction mechanism in reverse micellar extraction of MTGase was explored. By
using a molecular simulation study, the interaction mechanism of forward
extraction was investigated. The molecular simulation results reveal the
interaction of MTGase-water-surfactant is the major driving force for the forward
extraction. Further, the effect of ionic strength on molecular interactions in
backward extraction was investigated using 1H low-field nuclear magnetic
resonance (LF-NMR) and circular dichroism (CD) spectra. In backward extraction,
the interactions between water and the other two molecules (MTGase and surfactant
molecules) are enhanced while the interactions between target molecules (MTGase)
and the other two molecules (water and surfactant molecules) are weakened as the
ionic strength increases. Moreover, the effect of size exclusion on backward
extraction was also investigated. The results demonstrate size exclusion has
limit effect at high ionic strength, and the weakened interaction of MTGase-water
surfactant is the main reason causing the release of the target molecules in
backward extraction. This work might provide valuable reference to the MTGase
purification and downstream processing.
PMID- 28697932
TI - Influence of the mobile phase and molecular structure parameters on the retention
behavior of protonated basic solutes in chaotropic chromatography.
AB - In this study, we present novel insights into the pH-dependent retention behavior
of protonated basic solutes in chaotropic chromatography. To this end, two sets
of experiments were performed to distinguish between mobile phase pH and ionic
strength effects. In the first set, the ionic strength (I) was varied with the
concentration of NaPF6 and additives that adjusted the mobile phase pH, while in
the second set, I was kept constant by adding the appropriate amount of NaCl. In
each set, the retention behavior of 13 analytes was qualitatively examined in 21
chromatographic systems, which were defined by the NaPF6 concentration in their
aqueous phases (1-50mM) and the pH of their mobile phases (2, 3 or 4); the
acetonitrile content was fixed at 40%. The addition of NaCl significantly reduced
the differences among retention factors at studied pH values due to the effect of
the Na+ ions on PF6-adsorption to the stationary phase and the magnitude of the
consequential development of the surface potential. A quantitative description of
the observed phenomenon was obtained by an extended thermodynamic approach. The
contribution of ion-pair formation in the stationary phase to the retention of
the solutes was confirmed across models at the studied pH values in the set with
varying I. In the systems with a constant I, the shielding effect of the Na+ ions
on the surface charge lowered the attractive surface potential and diminished the
aforementioned interactions and hence the effect of the mobile phase pH on
analyte retention. Eventually, we developed a readily interpretable empirical
retention model that simultaneously takes into account analyte molecular
structures and the most relevant chromatographic factors. Its coefficients have
clear physical meaning, and owing to its good predictive capabilities, the model
could be successfully used to clarify the contributions of analyte molecular
structures and chromatographic factors to the specific processes underlying
separation in chaotropic chromatography.
PMID- 28697933
TI - A simple method for point-of-need extraction, concentration and rapid multi
mycotoxin immunodetection in feeds using aqueous two-phase systems.
AB - The rapid detection of mycotoxins in feed samples is becoming an increasingly
relevant challenge for the food production sector, in order to effectively
enforce current regulations and assure food and feed safety. To achieve rapid
mycotoxin detection, several biosensing strategies have been published, many
reaching assay times of the order of a few minutes. However, the vast majority of
these rely on sample preparation based on volatile organic solvents, often
comprising complex multi-step procedures and devoid of clean-up and/or
concentration effects. Here, a novel sample preparation methodology based on a
green, non-toxic and inexpensive polyethylene glycol-sodium citrate aqueous two
phase system is reported, providing single-step extraction and concentration of
three target mycotoxins within 20min: aflatoxin B1 (AFB1), ochratoxin A (OTA) and
deoxynivalenol (DON). With point-of-need applications in mind, the extraction
procedure was optimized and validated using a rapid multi-toxin microfluidic
competitive immunoassay. The assay was successfully tested with spiked complex
solid matrices including corn, soy, chickpea and sunflower-based feeds and limits
of detection of 4.6ngg-1+/-15.8%, 24.1ngg-1+/-8.1% and 129.7ngg-1+/-53.1% (+/-CV)
were obtained in corn for AFB1, OTA and DON, respectively. These sensitivities
are fit-for-purpose at the required regulatory and recommended limits for animal
feed, providing an effective and safe semi-quantitative mycotoxin analysis that
can be performed in the field.
PMID- 28697934
TI - Quantitative characterization of gold nanoparticles by size-exclusion and
hydrodynamic chromatography, coupled to inductively coupled plasma mass
spectrometry and quasi-elastic light scattering.
AB - The physicochemical characterization of nanoparticles (NPs) is of paramount
importance for tailoring and optimizing the properties of these materials as well
as for evaluating the environmental fate and impact of the NPs. Characterizing
the size and chemical identity of disperse NP sample populations can be
accomplished by coupling size-based separation methods to physical and chemical
detection methods. Informed decisions regarding the NPs can only be made,
however, if the separations themselves are quantitative, i.e., if all or most of
the analyte elutes from the column within the course of the experiment. We
undertake here the size-exclusion chromatographic characterization of Au NPs
spanning a six-fold range in mean size. The main problem which has plagued the
size-exclusion chromatography (SEC) analysis of Au NPs, namely lack of
quantitation accountability due to generally poor NP recovery from the columns,
is overcome by carefully matching eluent formulation with the appropriate
stationary phase chemistry, and by the use of on-line inductively coupled plasma
mass spectrometry (ICP-MS) detection. Here, for the first time, we demonstrate
the quantitative analysis of Au NPs by SEC/ICP-MS, including the analysis of a
ternary NP blend. The SEC separations are contrasted to HDC/ICP-MS (HDC:
hydrodynamic chromatography) separations employing the same stationary phase
chemistry. Additionally, analysis of Au NPs by HDC with on-line quasi-elastic
light scattering (QELS) allowed for continuous determination of NP size across
the chromatographic profiles, circumventing issues related to the shedding of
fines from the SEC columns. The use of chemically homogeneous reference materials
with well-defined size range allowed for better assessment of the accuracy and
precision of the analyses, and for a more direct interpretation of results, than
would be possible employing less rigorously characterized analytes.
PMID- 28697935
TI - Continuous countercurrent tangential chromatography for mixed mode post-capture
operations in monoclonal antibody purification.
AB - Continuous Countercurrent Tangential Chromatography (CCTC) has been shown to
demonstrate significant advantages over column chromatography including higher
productivity, lower operational pressure, disposable flow path, and lower resin
use. Previous applications of CCTC have been limited to initial capture of
monoclonal antibodies (mAb) from clarified cell culture harvest. In this present
article, a CCTC system was designed and tested for a post-capture antibody
purification step. Mixed mode cation exchange-hydrophobic interaction
chromatography resins with two different particle sizes were used to reduce host
cell protein (HCP), leached protein A, DNA, and aggregates from a mAb stream
after a protein A operation. Product output from CCTC was obtained at a steady
state concentration in sharp contrast to the periodic output of product in multi
column systems. The results show up to 101g of mAb/L of resin/hr productivity,
which is 10* higher than in a batch column. A 5% yield increase (95% with CCTC
vs. 90% in batch column) resulted from optimizing elution pH within a narrow
operational window (pH 4-4.5). Contaminant removal was found to be similar to
conventional column performance. Data obtained with the smaller particle size
resin showed faster binding kinetics leading to reduced CCTC system volume and
increased productivity. Buffer and water usage were modeled to show potential for
utilization of in-line mixing and buffer tank volume reduction. The experimental
results were used to perform a scale up exercise that predicts a compact CCTC
flow path for 500 and 2000L batches using commercially available membranes. These
results demonstrate the potential of using CCTC for post-capture operations as an
alternative to packed bed chromatography, and provide a framework for the design
and development of an integrated continuous bioprocessing platform based on CCTC
technology.
PMID- 28697936
TI - Radiofrequency Catheter Ablation For Atrial Fibrillation: Approaches And
Outcomes.
AB - Catheter ablation is now at the forefront of the management of symptomatic atrial
fibrillation (AF). Its role in paroxysmal AF is well defined with considerable
data supporting its role. Catheter ablation in persistent AF has been less
effective and the subject of considerable debate. Mechanistic studies have
demonstrated the critical role of pulmonary vein physiology in paroxysmal AF,
whereas the mechanisms that sustain persistent AF are not well understood.
Additional substrate ablation in persistent AF has not improved long-term
outcomes and the use of novel mapping technologies to assess rotor activity
remains controversial. This review will focus on the current understanding of the
mechanistic basis of paroxysmal and persistent AF, the role of catheter ablation
and, recent advances in the management of these complex arrhythmias.
PMID- 28697937
TI - Complications after endovascular treatment of hepatic artery stenosis after liver
transplantation.
AB - BACKGROUND: Hepatic artery stenosis (HAS) after liver transplantation can
progress to hepatic artery thrombosis (HAT) and a subsequent 30% to 50% risk of
graft loss. Although endovascular treatment of severe HAS after liver
transplantation has emerged as the dominant method of treatment, the potential
risks of these interventions are poorly described. METHODS: A retrospective
review of all endovascular interventions for HAS after liver transplantation
between August 2009 and March 2016 was performed at a single institution, which
has the largest volume of liver transplants in the United States. Severe HAS was
identified by routine surveillance duplex ultrasound imaging (peak systolic
velocity >400 cm/s, resistive index <0.5, and presence of tardus parvus
waveforms). RESULTS: In 1129 liver transplant recipients during the study period,
106 angiograms were performed in 79 patients (6.9%) for severe de novo or
recurrent HAS. Interventions were performed in 99 of 106 cases (93.4%) with
percutaneous transluminal angioplasty alone (34 of 99) or with stent placement
(65 of 99). Immediate technical success was 91%. Major complications occurred in
eight of 106 cases (7.5%), consisting of target vessel dissection (5 of 8) and
rupture (3 of 8). Successful endovascular treatment was possible in six of the
eight patients (75%). Ruptures were treated with the use of a covered coronary
balloon-expandable stent graft or balloon tamponade. Dissections were treated
with placement of bare-metal or drug-eluting stents. No open surgical
intervention was required to manage any of these complications. With a median of
follow-up of 22 months, four of eight patients (50%) with a major complication
progressed to HAT compared with one of 71 patients (1.4%) undergoing a hepatic
intervention without a major complication (P < .001). One patient required
retransplantation. Severe vessel tortuosity was present in 75% (6 of 8) of
interventions with a major complication compared with 34.6% (34 of 98) in those
without (P = .05). In the complication cohort, 37.5% (3 of 8) of the patients had
received a second liver transplant before intervention compared with 12.6% (9 of
71) of the patients in the noncomplication cohort (P = .097). CONCLUSIONS:
Although endovascular treatment of HAS is safe and effective in most patients,
target vessel injury is possible. Severe tortuosity of the hepatic artery and
prior retransplantation were associated with a twofold to threefold increased
risk of a major complication. Acute vessel injury can be managed successfully
using endovascular techniques, but these patients have a significant risk of
subsequent HAT and need close surveillance.
PMID- 28697938
TI - Outcomes of endovascular recanalization versus autogenous venous bypass for
thromboangiitis obliterans patients with critical limb ischemia due to
tibioperoneal arterial occlusion.
AB - OBJECTIVE: This study sought to compare the outcomes of endovascular
recanalization (ER) vs autogenous venous bypass (AVB) for tibioperoneal arterial
occlusion in thromboangiitis obliterans patients with critical lower limb
ischemia. METHODS: A total of 90 limbs in 75 patients, successfully treated with
ER (ER group, 35 patients, 43 limbs) and AVB (AVB group, 40 patients, 47 limbs)
for tibioperoneal arterial occlusions from January 2009 to December 2015 in a
single institution, were retrospectively analyzed. The characteristics and
outcomes were compared between the two groups. The primary outcome was the
amputation-free survival rate during follow-up; the secondary outcomes were
patency rates, immediate failure, periprocedural complications, and rates of
reintervention. Univariate and multivariate analysis to identify potentially
significant predictors of amputation-free survival and primary patency in the
whole study group was performed. RESULTS: Not all patients in the ER group were
bypass candidates because of unavailable runoff arteries or adequate conduit for
bypass. Other baseline characteristics were similar between groups. Patients in
the ER group had a much higher incidence of immediate failure (36.36% in
femoropopliteal segment and 65.52% in tibioperoneal segment vs 14.89% in AVB
bypass; P = .03 and < .001). Although patients in the ER group had a
significantly higher rate of reintervention (62.79% vs 27.66%; P < .001)
associated with a significantly lower primary patency rate (18.96% in
femoropopliteal segment and 14.37% in tibioperoneal segment vs 60.41% in AVB
bypass; P = .008 and < .001) and secondary patency rate (33.85% in
femoropopliteal segment and 21.29% in tibioperoneal segment vs 68.78% in AVB
bypass; P = .04 and .002) at 3 years, the amputation-free survival in the ER
group and AVB group was similar at 1 year (92.9% vs 93.2%; P = .81) and 3 years
(87.8% and 90.6%; P = .66). Univariate and multivariate analysis showed that the
presence of gangrene was independently associated with major amputation (hazard
ratio, 2.24; 95% confidence interval, 1.33-4.3; P = .02); however, the presence
of active ulcer was the only risk factor for poorer primary patency during follow
up (hazard ratio, 1.86; 95% confidence interval, 0.55-5.6; P = .04). CONCLUSIONS:
ER is a valid strategy for limb salvage in thromboangiitis obliterans patients
who are unsuitable for bypass, contributing an acceptable amputation-free
survival as high as with AVB, even though it is associated with lower patency
rates and a higher rate of reintervention.
PMID- 28697939
TI - Discussion.
PMID- 28697940
TI - Characterization of perioperative contralateral stroke after carotid
endarterectomy.
AB - OBJECTIVE: Contralateral stroke is an infrequent cause of perioperative stroke
after carotid endarterectomy (CEA). Whereas the risks of ipsilateral stroke
complicating CEA have been discriminated, factors that lead to contralateral
stroke are poorly defined. The purpose of this study was to identify the risk of
perioperative (30-day) contralateral stroke after CEA as well as predisposing
preoperative and operative factors. Its specific effect on long-term survival was
interrogated. METHODS: The Vascular Study Group of New England (VSGNE) was
queried from April 1, 2003, to February 29, 2016, for all CEAs. Duplicated
patients and those without complete data were excluded. Patients sustaining
contralateral stroke after CEA in the 30-day postoperative period were
identified. Demographic, preoperative, and operative factors were analyzed to
identify discriminators between those with and those without contralateral
stroke. Logistic regression modeling was performed to identify factors
independently associated with contralateral stroke. The effect of contralateral
stroke on 5-year survival was compared with patients with ipsilateral stroke and
no stroke using the Kaplan-Meier method. Log-rank testing compared survival
curves. RESULTS: There were 10,837 CEAs performed during the study. Average age
was 70.4 +/- 9.3 years; 6605 (61%) patients were male, and 40% (n = 4324) were
performed for symptoms. Most were current or former smokers (n = 8619 [80%]).
Coronary artery disease and congestive heart failure were identified in 31% and
8.6%, respectively. Overall, there were 190 strokes within 30 days of CEA (1.8%);
131 were ipsilateral (1.3%), and 59 (0.5%) patients were identified as having
contralateral perioperative stroke. Thirteen patients sustained bilateral stroke
(0.1%). Significant univariate associations included urgency (P = .0001),
ipsilateral stenosis severity (P = .004), length of operation (P = .0001), CEA
with coronary artery bypass graft (P = .0001), CEA with other arterial surgery (P
= .01), and CEA with proximal endovascular procedure (P = .03). Contralateral
occlusion (P = .06) and degree of contralateral carotid stenosis (P = .14) did
not correlate. After logistic regression analysis of significant univariate
anatomic and operative factors, length of procedure (odds ratio [OR], 1.08/15
minutes; 95% confidence interval [CI], 1.01-1.15; P = .02), urgency of operation
(OR, 2.5; 95% CI, 1.3-4.6; P = .006), and concomitant proximal endovascular
intervention (OR, 8.7; 95% CI, 4.5-31.2; P = .001) remained predictors of
contralateral stroke after CEA. Occurrence of both ipsilateral (P < .001) and
contralateral (P = .023) stroke significantly reduced 5-year survival compared
with those without stroke. There was no difference in the negative survival
effect based on laterality of stroke (P = .24). CONCLUSIONS: Contralateral stroke
after CEA is rare, affecting 0.5% of patients. Traditional risk reduction medical
therapy does not affect occurrence. Degree of contralateral stenosis, including
contralateral occlusion, does not predict perioperative contralateral stroke.
Urgency of operation, length of operation, and performance of concomitant,
ipsilateral endovascular intervention predict contralateral stroke risk with CEA.
Contralateral stroke affects long-term survival similar to ipsilateral stroke
after CEA.
PMID- 28697941
TI - Early outcomes of the conformable stent graft for acute complicated and
uncomplicated type B aortic dissection.
AB - OBJECTIVE: The objective of this study was to evaluate the safety, efficacy, and
outcomes of the conformable thoracic endograft (Conformable TAG Thoracic
Endoprosthesis [CTAG]; W. L. Gore & Associates, Flagstaff, Ariz) for acute
complicated and uncomplicated type B aortic dissection (TBAD). METHODS: Between
February and October 2016, 52 consecutive patients with acute complicated or
uncomplicated TBAD were treated with a CTAG device. We assessed safety,
complications, and device conformability using intraoperative angiography and
computed tomography angiography. The mean follow-up period was 8.2 +/- 3.5 months
(range, 4-12 months). RESULTS: All patients survived through the follow-up
period. No endoleaks, retrograde aortic dissection, distal new entry tear,
stroke, or paraplegia was observed postoperatively. Two patients (3.8%)
experienced minor wound hematomas without further treatment. Eleven patients
(21.2%) underwent a chimney technique to rebuild supra-arch vessels. A bird-beak
configuration was observed in seven (13.5%) patients, five of whom underwent a
chimney technique. Analysis of aortic remodeling showed that the minimal true
lumen area significantly increased in both complicated and uncomplicated acute
TBAD (P < .001 and P = .047, respectively). Likewise, the maximal false lumen
area significantly decreased in uncomplicated dissection (P = .006), but no
change in maximal false lumen area was detected in complicated dissection (P =
.32). CONCLUSIONS: Early outcomes indicate that the CTAG device provides reliable
clinical effectiveness and excellent conformability in treating acute complicated
and uncomplicated TBAD without risk of major complications. Studies with larger
sample sizes and longer follow-up periods are required to evaluate longer term
outcomes.
PMID- 28697942
TI - Outcomes for concomitant common iliac artery aneurysms after endovascular
abdominal aortic aneurysm repair.
AB - OBJECTIVE: This study evaluated the morbidity of endovascular abdominal aortic
aneurysm repair (EVAR) in patients with concomitant common iliac artery aneurysm
(CCIAA). METHODS: This was a retrospective review of all patients who underwent
elective EVAR from June 2006 through June 2012 at a single institution.
Demographics, comorbidities, preoperative presentation, intraoperative details,
and postoperative complications were tabulated. Patients with CCIAA were
categorized into three groups according to the distal extent of their iliac limb:
iliac limb extension into the external iliac artery with internal iliac artery
coil embolization (EE); flared iliac limb >=20 mm in diameter to the iliac
bifurcation (FL); and iliac limb <=20 mm ending proximal to the CCIAA (no-FL).
RESULTS: During this period, 627 consecutive patients underwent elective EVAR and
preoperative computed tomographic angiograms were available for 523 patients to
evaluate the presence of CCIAA. Of these, 211 patients (40.2%) had a CCIAA in at
least one common iliac artery, with a total of 307 aneurysmal arteries. Of these
307 aneurysmal arteries, 62 (20.2%) were treated with EE, 132 (43.0%) were
treated with FL, and 113 (36.8%) had a sufficient landing zone in the proximal
common iliac artery to use an iliac limb <=20 mm in diameter (no-FL). The overall
reintervention rate was 12.4% of patients, with a higher reintervention rate
between patients with CCIAA compared with those without (15.2% vs 10.9%; P =
.039). There were no significant differences in reintervention rates between the
EE, FL, and no-FL techniques (4.5% vs 4.8% vs 6.2%; P = .802) over a mean 59.8
months follow-up. The FL and EE techniques had a lower risk of distal endoleak
than the no-FL technique, but the difference was not statistically significant
(3.2% vs 2.3% vs 5.3% compared with 4.23% in the entire cohort). CONCLUSIONS:
Patients with CCIAA had a higher reintervention rate after EVAR for abdominal
aortic aneurysm compared with non-CCIAA patients. Of the techniques studied (EE,
FL, and no-FL), there was no significant difference in reintervention rates
between the three. All three techniques remain viable options for the
endovascular repair of CCIAA.
PMID- 28697943
TI - Ultrasonographic characteristics of accessory sex glands and spectral Doppler
indices of the internal iliac arteries in peri- and post-pubertal Dorper rams
raised in a subtropical climate.
AB - The aim of the present study was to determine and compare ultrasonographic
characteristics of accessory sex glands and spectral Doppler indices of the
internal iliac arteries in peri- and post-pubertal rams raised in a subtropical
climate. Forty-five Dorper rams were examined (24 rams aged 8-11 months and 21
rams aged 12-24 months). Digital images of all accessory sex glands were
subjected to morphometric and echotextural analyses, the latter using
commercially available image analytical software Image ProPlus(r). Physical and
morphological characteristics of semen and serum concentrations of testosterone
were also determined. The dimensions of the prostate gland (12.9+/-1.2 compared
with 14.2+/-2.7mm; mean+/-standard deviation) and bulbourethral glands (13.7+/
1.3 compared with 14.7+/-1.8mm) were greater (P=0.04) in sexually mature compared
with peri-pubertal rams. Pixel intensity of vesicular (181.5+/-20.8 compared with
164.8+/-26.8, P=0.02) and bulbourethral gland parenchyma (166.9+/-16.9 compared
with 141.8+/-29.1, P=0.001) was greater in peri-pubertal compared with sexually
mature rams. Semen could be collected by ejaculation into the artificial vagina
from 38% (8/21) of post-pubertal rams and 21% (5/24) of peri-pubertal animals
(P=0.03). Semen volume was positively correlated with peak systolic velocity
(PSV) and end-diastolic velocity (EDV) in the internal iliac arteries (r=0.79,
P=0.001 and r=0.67, P=0.01, respectively), while spermatic vigor and progressive
motility were inversely related to circulating concentrations of testosterone (r=
0.69, P=0.009 and r=-0.61, P=0.03, respectively). In summary, the attainment of
sexual maturity in the rams of the present study was associated with an
enlargement of the prostate and bulbourethral glands, and with the shift in
echotextural attributes of vesicular and bulbourethral glands. Circulating
testosterone concentrations and Doppler blood flow indices of the ram's internal
iliac arteries are significant predictors of sperm progressive motility, vigor
and the amount of ejaculate.
PMID- 28697944
TI - Vocabulary learning benefits from REM after slow-wave sleep.
AB - Memory reactivation during slow-wave sleep (SWS) influences the consolidation of
recently acquired knowledge. This reactivation occurs spontaneously during sleep
but can also be triggered by presenting learning-related cues, a technique known
as targeted memory reactivation (TMR). Here we examined whether TMR can improve
vocabulary learning. Participants learned the meanings of 60 novel words.
Auditory cues for half the words were subsequently presented during SWS in an
afternoon nap. Memory performance for cued versus uncued words did not differ at
the group level but was systematically influenced by REM sleep duration.
Participants who obtained relatively greater amounts of REM showed a significant
benefit for cued relative to uncued words, whereas participants who obtained
little or no REM demonstrated a significant effect in the opposite direction. We
propose that REM after SWS may be critical for the consolidation of highly
integrative memories, such as new vocabulary. Reactivation during SWS may allow
newly encoded memories to be associated with other information, but this
association can include disruptive linkages with pre-existing memories.
Subsequent REM sleep may then be particularly beneficial for integrating new
memories into appropriate pre-existing memory networks. These findings support
the general proposition that memory storage benefits optimally from a cyclic
succession of SWS and REM.
PMID- 28697945
TI - Dynamic hydrographic variations in northwestern Arabian Gulf over the past three
decades: Temporal shifts and trends derived from long-term monitoring data.
AB - Hydrographic variables were monitored in northwestern Arabian Gulf over the past
three decades and the time-series data were statistically analyzed. The results
show that while salinity has undergone several shifts, seawater temperature
exhibited a steady increasing trend since the 1980s. The observed salinity shows
strong correlation with Shatt Al-Arab River discharge indicating primary
contribution of freshwater to salinity among other factors (evaporation and
desalination effluent). Recent data show that salinity is at its highest level in
the last 30years with less pronounced seasonal variability in response to severe
decline in the freshwater runoff into the northwestern Arabian Gulf. The changes
in hydrographic conditions may have significant implications on hydrodynamics,
water quality, and ecosystems in the Gulf. Thus, cooperation among the concerned
countries - both coastal and riparian nations - would be essential for prevention
of further major changes in the Gulf.
PMID- 28697946
TI - Characterization and source apportionment of polycyclic aromatic hydrocarbons
(pahs) in the sediments of gulf of Pozzuoli (Campania, Italy).
AB - Most of the literature reports on the impact of the former Bagnoli brownfield on
the pollution of Bagnoli Bay, embedded in the Gulf of Pozzuoli (GoP). Thus, we
studied concentrations, types and sources of sixteen PAHs (EPA) in sediments at
22 sites along 5 transects covering the entire area of GoP. Outstanding levels of
PAHs were found, varying from 7.1MUgg-1 to 2.5 E+3MUgg-1. Sediments collected at
sites far away from Bagnoli were found to be polluted to a similar extent than
those facing the brownfield site, with values>100MUgg-1. Total PAHs levels in the
sediments of GoP were higher by thirty-eleven thousand fold than those reported
by other studies from various marine sites in the world. Transit axes of fine and
very fine sands and diagnostic indexes revealed a common pyrolytic PAHs pollution
spreading from the Bagnoli plant to all GoP.
PMID- 28697947
TI - Synaptic distribution and plasticity in primary auditory cortex (A1) exhibits
laminar and cell-specific changes in the deaf.
AB - The processing sequence through primary auditory cortex (A1) is impaired by
deafness as evidenced by reduced neuronal activation in A1 of cochlear-implanted
deaf cats. Such a loss of neuronal excitation should be manifest as changes in
excitatory synaptic number and/or size, for which the post-synaptic correlate is
the dendritic spine. Therefore, the present study sought evidence for this
functional disruption using Golgi-Cox/light microscopic techniques that examined
spine-bearing neurons and their dendritic spine features across all laminae in A1
of early-deaf (ototoxic lesion <1 month; raised into adulthood >16 months) and
hearing cats. Surprisingly, in the early-deaf significant increases in spine
density and size were observed in the supragranular layers, while significant
reductions in spine density were observed for spiny non-pyramidal, but not
pyramidal, neurons in the granular layer. No changes in dendritic spine density
consistent with loss of excitatory inputs were seen for infragranular neurons.
These results indicate that long-term early-deafness induces plastic changes in
the excitatory circuitry of A1 that are laminar and cell-specific. An additional
finding was that, unlike the expected abundance of stellate neurons that
characterize the granular layer of other primary sensory cortices, pyramidal
neurons predominate within layer 4 of A1. Collectively, these observations are
important for understanding how neuronal connectional configurations contribute
to region-specific processing capabilities in normal brains as well as those with
altered sensory experiences.
PMID- 28697948
TI - Catalyzing improvements in ALL therapy with asparaginase.
AB - Asparaginase remains a cornerstone of ALL therapy and is one of the key
contributing factors to improved outcomes in adolescent and young adult (AYA)
patients treated on pediatric protocols. Asparagine depletion has been associated
with improved outcomes in ALL patients; this has led to an increased emphasis on
optimizing asparagine depletion in ALL patients of all ages. To ensure adequate
asparagine depletion, the use of therapeutic drug monitoring of asparaginase
therapy holds much promise, yet remains underutilized in practice. Data regarding
asparaginase activity level monitoring and associated outcomes are reviewed, and
an evidence-based asparaginase activity level monitoring algorithm is presented.
Finally, unique management strategies for key asparaginase toxicities in ALL
patients are discussed, as well as a discussion of novel asparaginase
formulations on the horizon.
PMID- 28697949
TI - An elderly man with hemolysis and myelophthisic anemia.
PMID- 28697950
TI - Sodium levels on admission are associated with mortality risk in hospitalized
patients.
AB - AIMS: Abnormal sodium values are common among hospitalized patients. We aimed to
investigate the association of admission sodium values and mortality. METHODS:
Historical prospectively data of adult patients hospitalized to medical wards
between January 2011 and December 2013. Admission sodium values were classified
to five categories: severe hyponatremia (<125mEq/L), mild hyponatremia (125
135mEq/L), normal sodium values (135-145mEq/L), mild hypernatremia (145-150mEq/L)
and severe hypernatremia (>150mEq/L). Main outcomes were length of
hospitalization, in-hospital mortality and mortality at the end-of-follow-up.
RESULTS: The cohort included 27,889 patients (mean age 67+/-18years, 52% males).
The total follow-up was 1065days. Most patients had normal sodium values (76%),
22% had hyponatremia, 3% had hypernatremia. Mean age increased with increase in
severity of hyponatremia or hypernatremia. Median length of hospitalization was
longer with mild and severe hypernatremia (7 and 5days, respectively) or with
mild and severe hyponatremia (4 and 4days, respectively), compared to normal
sodium levels (3days). Compared to in-hospital mortality with normal sodium
levels (5%), mortality was higher with mild and severe hyponatremia (9% and 14%,
respectively) and was highest with mild (28%), and severe hypernatremia (52%).
Mortality rate at the end of follow-up was 28% with normal sodium levels, 44% and
48% with mild and severe hyponatremia, 66% and 90% with mild and severe
hypernatremia, respectively. CONCLUSIONS: Abnormal sodium values on admission
were associated with longer hospitalization and increased short- and long-term
mortality. Mortality risk was higher with hypernatremia, compared to
hyponatremia.
PMID- 28697951
TI - In search of albumin: An unusual case of lower limb edema.
PMID- 28697953
TI - 3D in vitro models of liver fibrosis.
AB - Animal testing is still the most popular preclinical assessment model for liver
fibrosis. To develop efficient anti-fibrotic therapies, robust and representative
in vitro models are urgently needed. The most widely used in vitro fibrosis model
is the culture-induced activation of primary rodent hepatic stellate cells. While
these cultures have contributed greatly to the current understanding of hepatic
stellate cell activation, they seem to be inadequate to cover the complexity of
this regenerative response. This review summarizes recent progress towards the
development of 3D culture models of liver fibrosis. Thus far, only a few hepatic
culture systems have successfully implemented hepatic stellate cells (or other
non-parenchymal cells) into hepatocyte cultures. Recent advances in bioprinting,
spheroid- and precision-cut liver slice cultures and the use of microfluidic
bioreactors will surely lead to valid 3D in vitro models of liver fibrosis in the
near future.
PMID- 28697952
TI - Pharmacological and physical vessel modulation strategies to improve EPR-mediated
drug targeting to tumors.
AB - The performance of nanomedicine formulations depends on the Enhanced Permeability
and Retention (EPR) effect. Prototypic nanomedicine-based drug delivery systems,
such as liposomes, polymers and micelles, aim to exploit the EPR effect to
accumulate at pathological sites, to thereby improve the balance between drug
efficacy and toxicity. Thus far, however, tumor-targeted nanomedicines have not
yet managed to achieve convincing therapeutic results, at least not in large
cohorts of patients. This is likely mostly due to high inter- and intra-patient
heterogeneity in EPR. Besides developing (imaging) biomarkers to monitor and
predict EPR, another strategy to address this heterogeneity is the establishment
of vessel modulation strategies to homogenize and improve EPR. Over the years,
several pharmacological and physical co-treatments have been evaluated to improve
EPR-mediated tumor targeting. These include pharmacological strategies, such as
vessel permeabilization, normalization, disruption and promotion, as well as
physical EPR enhancement via hyperthermia, radiotherapy, sonoporation and
phototherapy. In the present manuscript, we summarize exemplary studies showing
that pharmacological and physical vessel modulation strategies can be used to
improve tumor-targeted drug delivery, and we discuss how these advanced
combination regimens can be optimally employed to enhance the (pre-) clinical
performance of tumor-targeted nanomedicines.
PMID- 28697954
TI - Antinociceptive action of NOP and opioid receptor agonists in the mouse orofacial
formalin test.
AB - Nociceptin/orphanin FQ (N/OFQ) modulates several biological functions, including
pain transmission via selective activation of a specific receptor named NOP. The
aim of this study was the investigation of the antinociceptive properties of NOP
agonists and their interaction with opioids in the trigeminal territory. The
orofacial formalin (OFF) test in mice was used to investigate the antinociceptive
potential associated to the activation of NOP and opioid receptors. Mice
subjected to OFF test displayed the typical biphasic nociceptive response and
sensitivity to opioid and NSAID drugs. Mice knockout for the NOP gene displayed a
robust pronociceptive phenotype. The NOP selective agonist Ro 65-6570 (0.1-1mgkg
1) and morphine (0.1-10mgkg-1) elicited dose dependent antinociceptive effects in
the OFF with the alkaloid showing larger effects; the isobologram analysis of
their actions demonstrated an additive type of interaction. The mixed NOP/opioid
receptor agonist cebranopadol elicited potent (0.01-0.1mgkg-1) and robust
antinociceptive effects. In the investigated dose range, all drugs did not modify
the motor performance of the mice in the rotarod test. Collectively the results
of this study demonstrated that selective NOP agonists and particularly mixed
NOP/opioid agonists are worthy of development as innovative drugs to treat
painful conditions of the trigeminal territory.
PMID- 28697956
TI - Overimaging and the "Found Down" Patient: An Opportunity to Set the Standard of
Care.
PMID- 28697955
TI - Nesfatin-1 inhibits voltage gated K+ channels in pancreatic beta cells.
AB - The anorexigenic neuropeptide NEFA/nucleobindin 2 (NUCB2)/nesfatin-1-containing
neurons are distributed in the brain regions involved in feeding regulation. In
spite of the growing knowledge of its physiological functions through extensive
studies, its molecular mechanism of reaction, including its receptor, remains
unknown. NUCB2/nesfatin-1 is also involved in various peripheral regulations,
including glucose homeostasis. In pancreatic beta-cells, NUCB2/nesfatin-1 is
reported to enhance glucose-stimulated insulin secretion (GSIS) but its exact
mechanism remains unknown. To clarify this mechanism, we measured the effect of
nesfatin-1 on the electrical activity of pancreatic beta-cells. Using mouse
primary beta cells, we measured changes in the ATP-sensitive K+ (KATP) channel
current, the voltage-gated K+ (Kv) channel current, and insulin secretion upon
application of nesfatin-1. Nesfatin-1 inhibited the Kv channel, but KATP channel
activity was unaffected. Nesfatin-1 enhanced insulin secretion to a same level as
Kv channel blocker tetraethylammonium (TEA). The effect was not further enhanced
when nesfatin-1 and TEA were applied simultaneously. The inhibition binding assay
with [125I]nesfatin-1 in Kv2.1 channels, major contributor of Kv current in beta
cell, expressing HEK239 cells indicated the binding of nesfatin-1 on Kv2.1
channel. Because Kv channel inhibition enhances insulin secretion under high
glucose conditions, our present data suggest a possible mechanism of nesfatin-1
on enhancing GSIS through regulation of ion channels rather than its unidentified
receptor.
PMID- 28697957
TI - Seven Lessons for Implementing a Health Information System.
PMID- 28697958
TI - Reducing Portable Chest Radiography in the Intensive Care Unit.
PMID- 28697959
TI - Cancer Imaging Fellowship Training: Utility and Added Value in the Modern Era.
PMID- 28697960
TI - What Ails Thee? The Myth of the Holy Grail and Physician Burnout.
PMID- 28697961
TI - Fifteen Year Results of Radiofrequency Ablation, Using VNUS Closure, for the
Abolition of Truncal Venous Reflux in Patients with Varicose Veins.
AB - OBJECTIVES: Endovenous thermal ablation (EVTA) of varicose veins was introduced
in the late 1990s with radiofrequency ablation (RFA) using the VNUS Closure
device. The results of the original VNUS Closure device for the abolition of
truncal venous reflux at 15 years are reported. METHODS: A prospective audit of a
group of patients treated with VNUS Closure 15 years previously was carried out,
using clinical assessment and duplex ultrasound. A total of 189 patients were
treated with VNUS Closure between March 1999 and December 2001 and were invited
for clinical assessment (subjective and objective) and duplex ultrasonography
(DUS) to assess treatment outcome and de novo disease progression. DUS outcome of
the treated vein was graded: 1, complete success (complete atrophy); 2, partial
success (> 1 patent section; none giving rise to recurrent varicose veins); 3,
partial failure (>= 1 patent sections giving rise to recurrent varicose veins);
4, complete failure. RESULTS: Fifty-eight patients (91 legs, 101 truncal veins)
returned for follow-up DUS, giving a 31.5% response rate (many patients had moved
or had died in the 15 years). Two truncal veins had been excluded following
treatment elsewhere presumably for partial or complete failure. At a mean of 15.4
years post-procedure, 51 (56%) reported no varicose veins, 58 (100%) that they
were pleased that they had the procedure and 57 (98%) that they would recommend
the procedure. DUS showed 88% of patients achieved success with no clinical
recurrence in the originally treated veins. De novo reflux was identified in 47
of 91 legs (51.6%), showing disease progression in veins that were originally
competent. CONCLUSIONS: RFA with VNUS Closure achieved excellent long-term
technical success in treating venous reflux in truncal veins 15 years post
procedure, demonstrated by DUS. This bodes well for the increased use of EVTA in
treating truncal vein reflux.
PMID- 28697962
TI - CON4EI: EpiOcularTM Eye Irritation Test (EpiOcularTM EIT) for hazard
identification and labelling of eye irritating chemicals.
AB - Assessment of the acute eye irritation potential is part of the international
regulatory requirements for testing of chemicals. The objective of the CON4EI
project was to develop tiered testing strategies for eye irritation assessment. A
set of 80 reference chemicals (38 liquids and 42 solids) was tested with eight
different methods. Here, the results obtained with the EpiOcularTM Eye Irritation
Test (EIT), adopted as OECD TG 492, are shown. The primary aim of this study was
to evaluate of the performance of the test method to discriminate between
chemicals not requiring classification for serious eye damage/eye irritancy (No
Category) and chemicals requiring classification and labelling. In addition, the
predictive capacity in terms of in vivo drivers of classification (i.e. corneal
opacity, conjunctival redness and persistence at day 21) was investigated.
EpiOcularTM EIT achieved a sensitivity of 97%, a specificity of 87% and accuracy
of 95% and also confirmed its excellent reproducibility (100%) from the original
validation. The assay was applicable to all chemical categories tested in this
project and its performance was not limited to the particular driver of the
classification. In addition to the existing prediction model for dichotomous
categorization, a new prediction model for Cat 1 is suggested.
PMID- 28697963
TI - A new model for including the effect of fly ash on biochemical methane potential.
AB - The modelling of the effect of trace elements on anaerobic digestion, and
specifically the effect of fly ash, has been scarcely studied. Thus, the present
work was aimed at the development of a new function that allows accumulated
methane models to predict the effect of FA on the volume of methane accumulation.
For this, purpose five fly ash concentrations (10, 25, 50, 250 and 500mg/L) using
raw and pre-treated sewage sludge were used to calibrate the new function, while
three fly ash concentrations were used (40, 150 and 350mg/L) for validation.
Three models for accumulated methane volume (the modified Gompertz equation, the
logistic function, and the transfer function) were evaluated. The results showed
that methane production increased in the presence of FA when the sewage sludge
was not pre-treated, while with pretreated sludge there is inhibition of methane
production at FA concentrations higher than 50mg/L. In the calibration of the
proposed function, it fits well with the experimental data under all the
conditions, including the inhibition and stimulating zones, with the values of
the parameters of the methane production models falling in the range of those
reported in the literature. For validation experiments, the model succeeded in
representing the behavior of new experiments in both the stimulating and
inhibiting zones, with NRMSE and R2 ranging from 0.3577 to 0.03714 and 0.2209 to
0.9911, respectively. Thus, the proposed model is robust and valid for the
studied conditions.
PMID- 28697964
TI - Technical properties of biomass and solid recovered fuel (SRF) co-fired with
coal: Impact on multi-dimensional resource recovery value.
AB - The power plant sector is adopting the co-firing of biomass and solid recovered
fuel (SRF) with coal in an effort to reduce its environmental impact and costs.
Whereas this intervention contributes to reducing carbon emissions and those of
other pollutants related with the burning of fossil fuel, it may also result in
hidden impacts that are often overlooked. When co-firing, the physical and
chemical properties of the mixed fuels and the subsequent technical implications
on the process performance and by-products are significant. Interconnections
between multiple values nested within four domains of value, i.e. environmental,
economic, technical and social, mean that changes in the one domain (in the co
firing case, the technical one) can have considerable implications in the other
domains as well. In this study, using a systematic and flexible approach to
conceptualising multi-dimensional aspects associated with the co-firing of
biomass and SRF with coal, we unveil examples of such interconnections and
implications on overall value delivered through the use and recovery of waste
resources. Such an analysis could underpin the selection of useful metrics
(quantitative or semi-quantitative descriptors) for enabling a systemic multi
dimensional value assessment, and value's distribution amongst interconnected
parts of resource recovery systems; key in enabling sound analysis and decision
making.
PMID- 28697965
TI - Beyond organoids: In vitro vasculogenesis and angiogenesis using cells from
mammals and zebrafish.
AB - The ability to culture complex organs is currently an important goal in
biomedical research. It is possible to grow organoids (3D organ-like structures)
in vitro; however, a major limitation of organoids, and other 3D culture systems,
is the lack of a vascular network. Protocols developed for establishing in vitro
vascular networks typically use human or rodent cells. A major technical
challenge is the culture of functional (perfused) networks. In this rapidly
advancing field, some microfluidic devices are now getting close to the goal of
an artificially perfused vascular network. Another development is the emergence
of the zebrafish as a complementary model to mammals. In this review, we discuss
the culture of endothelial cells and vascular networks from mammalian cells, and
examine the prospects for using zebrafish cells for this objective. We also look
into the future and consider how vascular networks in vitro might be successfully
perfused using microfluidic technology.
PMID- 28697966
TI - THEMIS: Two Models, Different Thresholds.
AB - THEMIS, a recently identified T-lineage-restricted protein, is the founding
member of a large metazoan protein family. Gene inactivation studies have
revealed a critical requirement for THEMIS during thymocyte positive selection,
implicating THEMIS in signaling downstream of the T cell antigen receptor (TCR),
but the mechanistic underpinnings of THEMIS function have remained elusive. A
previous model posited that THEMIS prevents thymocytes from inappropriately
crossing the positive/negative selection threshold by dampening TCR signaling.
However, new data suggest an alternative model where THEMIS enhances TCR
signaling enabling thymocytes to reach the threshold for positive selection,
avoiding death by neglect. We review the data supporting each model and conclude
that the preponderance of evidence favors an enhancing function for THEMIS in TCR
signaling.
PMID- 28697967
TI - "New" bronchopulmonary dysplasia and chronic lung disease.
AB - Bronchopulmonary dysplasia (BPD) is the major cause of chronic lung disease and
morbidity in preterm infants. Since it was first described fifty years ago, the
epidemiology, pathogenesis, and treatment for BPD has changed dramatically. This
review summarizes these changes and the clinical outcomes for infants diagnosed
with BPD.
PMID- 28697968
TI - Update on pathophysiology and treatment of childhood obstructive sleep apnea
syndrome.
AB - Obstructive sleep apnea syndrome (OSAS) is common in childhood and is
characterized by recurrent upper airway obstructive events during sleep that
produce significant neurocognitive and cardiovascular sequelae. The
pathophysiology of childhood OSAS is complex and involves mechanical airway
obstruction often secondary to adenotonsillar hypertrophy. However, neuromotor
abnormalities and instability of central ventilatory control are also implicated.
Several surgical and non-surgical treatment options for childhood OSAS are
available, and will be discussed. Some of these include adenotonsillectomy,
lingual tonsillectomy, supraglottoplasty, continuous positive airway pressure
(CPAP), rapid maxillary expansion, oral appliance therapy, anti-inflammatory
treatments, and supplemental oxygen.
PMID- 28697969
TI - Childhood severe asthma: New insights on remodelling and biomarkers.
AB - Severe asthma in children is characterised by severe and multiple aeroallergen
sensitisation, food allergy, eosinophilic airway inflammation and airway
remodelling. However, it is a heterogeneous disease with considerable variability
in the manifestation of each of these characteristics between patients. Recent
data from mechanistic studies that have used translational approaches including
neonatal mouse models and airway bronchoscopic samples, have shown specific
molecular mediators that drive remodelling and steroid resistance in paediatric
severe asthma will be discussed. The importance of undertaking studies using age
appropriate models and primary cells from children to identify novel therapeutic
targets will be highlighted.
PMID- 28697970
TI - Cystic fibrosis: Priorities and progress for future therapies.
AB - Significant improvement in the survival of patients with CF has been achieved in
the last decades. The improved clinical status of the patients is mainly the
result of a better understanding of the natural course of infection and
inflammation in CF that has led to the implementation of strategies that increase
the life expectancy and quality of life of the patients. These strategies include
prompt diagnosis, timely and aggressive nutritional support, augmentation of MCC
and improved mucous drainage, initiation of antimicrobial and anti-inflammatory
therapy as soon as possible, early treatment of acute exacerbations,
implementation of effective hygienic measures in and outside CF centers and
prompt identification and treatment of CF-related complications. Treatment at a
specialized CF center by a multidisciplinary dedicated team, including frequent
visits, and periodic routine tests are essential to detect and treat early
changes. Adherence to these therapies is challenging. Maintaining patients in
optimal status will allow them to benefit from future treatments designed to
correct or modify the basic genetic defect associated with CFTR by gene
replacement therapy or pharmacological interventions currently under development.
These new therapies are expected to further increase life expectancy of the
patients.
PMID- 28697971
TI - Methodology for Developing a New EFNEP Food and Physical Activity Behaviors
Questionnaire.
AB - OBJECTIVE: Research methods are described for developing a food and physical
activity behaviors questionnaire for the Expanded Food and Nutrition Education
Program (EFNEP), a US Department of Agriculture nutrition education program
serving low-income families. DESIGN: Mixed-methods observational study. The
questionnaire will include 5 domains: (1) diet quality, (2) physical activity,
(3) food safety, (4) food security, and (5) food resource management. A 5-stage
process will be used to assess the questionnaire's test-retest reliability and
content, face, and construct validity. SETTING: Research teams across the US will
coordinate questionnaire development and testing nationally. PARTICIPANTS:
Convenience samples of low-income EFNEP, or EFNEP-eligible, adult participants
across the US. INTERVENTIONS: A 5-stage process: (1) prioritize domain concepts
to evaluate (2) question generation and content analysis panel, (3) question
pretesting using cognitive interviews, (4) test-retest reliability assessment,
and (5) construct validity testing. MAIN OUTCOME MEASURE: A nationally tested
valid and reliable food and physical activity behaviors questionnaire for low
income adults to evaluate EFNEP's effectiveness. ANALYSIS: Cognitive interviews
will be summarized to identify themes and dominant trends. Paired t tests (P <=
.05) and Spearman and intra-class correlation coefficients (r > .5) will be
conducted to assess reliability. Construct validity will be assessed using
Wilcoxon t test (P <= .05), Spearman correlations, and Bland-Altman plots.
PMID- 28697972
TI - Neuroprotection of edaravone on the hippocampus of kainate-induced epilepsy rats
through Nrf2/HO-1 pathway.
AB - Epilepsy is a severe and chronic neurological disease. Edaravone is an effective
free radical scavenger and has been reported to prevent neuronal loss induced by
Kainate (KA). However, the molecular mechanisms by which edaravone inhibits KA
induced neuron injury remain elusive. Seventy adult male Wistar rats were
randomly divided into 7 groups. For KA treatment, Kainate (4 MUg/kg) were
administrated in the right hippocampus CA3 region with sereotactic technique. And
for edaravone treatment, the rats were intraperitoneal injection with edaravone
(10 mg kg - 1 d - 1). All rats were sacrificed on the seven day after the
injection of KA. Histological changes of the hippocampus, CA1, CA3 and CA4 were
observed under thionine staining. Histological changes of CA1 and CA3 were
divided into the following 4 grades (histological grade,HG) under light
microscope. The release of inflammatory cytokines was measured by ELISA assay.
The inflammatory proteins and Nrf2 and HO-1 expression were determined by
quantitative real time PCR (qRT-PCR) and Western blots analysis. Treatment with
edaravone increased the neuronal density and decreased the neuronal damage degree
in the CA1, CA3 subfield induced by KA. Besides, edaravone reduced the
downregulation of the mRNA and protein expression levels of Nrf2 and HO-1 induced
by KA. Moreover, edaravone decreased the levels of NF-kappaB (P65) and
proinflammatory cytokines TNF-alpha, IL-1beta and IL-6 and the inflammatory
proteins expression levels, HMGB1, nNOS, iNOS and eNOS in the hippocampus.
However, introduction of Nrf2-siRNA and HO-1 inhibitor (Znpp) reversed the
effects of edaravone on KA-injected rats. Edaravone can protect hippocampal
neurons from damage in KA-induced epilepsy rats through Nrf2/HO-1 pathway.
PMID- 28697973
TI - Traffic jam hypothesis: Relationship between endocytic dysfunction and
Alzheimer's disease.
AB - Membrane trafficking pathways, like the endocytic pathway, carry out fundamental
cellular processes that are essential for normal functioning. One such process is
regulation of cell surface receptor signaling. A growing body of evidence
suggests that beta-amyloid protein (Abeta) plays a key role in Alzheimer's
disease (AD) pathogenesis. Cleavage of Abeta from its precursor, beta-amyloid
precursor protein (APP), occurs through the endocytic pathway in neuronal cells.
In early-stage AD, intraneuronal accumulation of abnormally enlarged endosomes is
common, indicating that endosome trafficking is disrupted. Strikingly, genome
wide association studies reveal that several endocytosis-related genes are
associated with AD onset. Also, recent studies demonstrate that alteration in
endocytosis induces not only Abeta pathology but also the propagation of tau
protein pathology, another key pathological feature of AD. Endocytic dysfunction
can disrupt neuronal physiological functions, such as synaptic vesicle transport
and neurotransmitter release. Thus, "traffic jams" in the endocytic pathway may
be involved in AD pathogenesis and may serve as a novel target for the
development of new therapeutics.
PMID- 28697974
TI - A possible desensitized state conformation of the human alpha7 nicotinic
receptor: A molecular dynamics study.
AB - The determination of the conformational states corresponding to diverse
functional roles of ligand gated ion channels is subject of intense investigation
with various techniques, from X-rays structure determination to electrophysiology
and computational modeling. Even with a certain number of structures becoming
recently available, only few major structural features distinguishing conductive
open channel from the non conductive resting protein have been highlighted, while
high-resolution details are still missing. The characterization of the
desensitized conformation(s) is even more complex, and only few specific
characteristics have been identified. Furthermore, experimental data provide
conflicting information for different ion channels, adding further complexity to
the topic. Desensitization is defined as the transition of the agonist-bound open
channel into an ion channel configuration inactive even in the presence of
agonists. In this work, we analyze a conformation corresponding to a non
conductive state obtained via molecular dynamics simulations of a homology model
of the human alpha7 nicotinic receptor complexed with agonists. We highlight some
characteristics that could associate it to a desensitized state. The obtained
structure is assessed against experimental data for other ligand gated ion
channels that have been putatively associated to active, inactive and
desensitized conditions.
PMID- 28697975
TI - Effects of sanitation on cognitive development and school absence: A systematic
review.
AB - OBJECTIVE: We undertook this systematic review to explore the relationship
between sanitation and learning outcomes, specifically cognitive development and
absence. METHODS: We searched leading databases to identify experimental and
observational studies that address the effect of sanitation on our outcomes of
interest. We identified 17 studies that met the review's eligibility criteria,
four reporting on measures of cognitive development, 12 on school absence (with
two studies reporting on school and work absence), and one study that reported on
both outcomes. We assessed the risk of bias of individual studies as well as the
overall strength of evidence for each outcome. Because of fundamental differences
among the studies in terms of sanitation exposure and outcome measurement,
pooling results via meta-analysis was deemed inappropriate so a descriptive
review is presented. RESULTS: Studies reported that access to household
sanitation was associated with measures of improved cognitive ability in
children. However, collectively these studies were rated by GRADE as poor
methodological quality with significant potential for confounding and bias,
including publication bias. Studies on the association between household,
community or school sanitation and school absence yielded mixed results. Some
sanitation studies reported lower absence while others reported higher absence.
Only the two randomized controlled trials reported no overall effects on absence
even when combining sanitation with water supply improvements and hygiene
promotion. Study quality as assessed by GRADE was again generally poor.
CONCLUSION: While studies to date provide some support for positive effects from
sanitation on cognitive development, the effects on school absence are uncertain.
Differences in effects may be due to differences in study settings, type of
sanitation exposure and most notably in outcome definitions. Further research in
multiple settings using rigorous study designs and measuring intermediate
outcomes such as exposure can help determine the effects of sanitation on these
important learning outcomes.
PMID- 28697976
TI - Anaerobic bioconversion of food waste into energy: A critical review.
PMID- 28697977
TI - Potential biomedical applications of marine algae.
AB - Functional components extracted from algal biomass are widely used as dietary and
health supplements with a variety of applications in food science and technology.
In contrast, the applications of algae in dermal-related products have received
much less attention, despite that algae also possess high potential for the uses
in anti-infection, anti-aging, skin-whitening, and skin tumor treatments. This
review, therefore, focuses on integrating studies on algae pertinent to human
skin care, health and therapy. The active compounds in algae related to human
skin treatments are mentioned and the possible mechanisms involved are described.
The main purpose of this review is to identify serviceable algae functions in
skin treatments to facilitate practical applications in this high-potential area.
PMID- 28697978
TI - Functional characterization of BdB1, a well-conserved carboxylesterase among
tephritid fruit flies associated with malathion resistance in Bactrocera dorsalis
(Hendel).
AB - There are many evidences that insect carboxylesterase possess important
physiological roles in xenobiotic metabolism and are implicated in the
detoxification of organophosphate (OP) insecticides. Despite the ongoing
resistance development in the oriental fruit fly, Bactrocera dorsalis (Hendel),
the molecular basis of carboxylesterase and its ability to confer OP resistance
remain largely obscure. This study was initiated to provide a better
understanding of carboxylesterase-mediated resistance mechanism in a tephritid
pest fly. Here, we narrow this research gap by demonstrating a well-conserved
esterase B1 gene, BdB1, mediates malathion resistance development via gene
upregulation with the use of a laboratory selected malathion-resistant strain
(MR) of B. dorsalis. No sequence mutation of BdB1 was detected between MR and the
susceptible strain (MS) of B. dorsalis. BdB1 is predominantly expressed in the
midgut, a key insect tissue for detoxification. As compared with transcripts in
MS, BdB1 was significantly more abundant in multiple tissues in the MR. RNA
interference (RNAi)-mediated knockdown of BdB1 significantly increased malathion
susceptibility. Furthermore, heterologous expression along with cytotoxicity
assay revealed BdB1 could probably have the function of malathion detoxification.
PMID- 28697979
TI - The effect of endothelial cell activation and hypoxia on placental chorionic
mesenchymal stem/stromal cell migration.
AB - INTRODUCTION: Chorionic mesenchymal stem/stromal cells (CMSC) can be isolated
from the placenta in large numbers. Although their functions are yet to be fully
elucidated, they have a role in tissue development and repair. To fulfil such a
role, CMSC must be able to migrate to the microenvironment of the injury site.
This process is not fully understood and the aim of this study therefore, was to
examine in vitro CMSC migration in response to tissue inflammation and hypoxic
conditioning. METHODS: CMSC were derived from the chorionic villi. A trans
endothelium migration (TEM) assay was used to study CMSC migration through an
activated endothelial cell monolayer using the HMEC-1 cell line. A cytokine array
was used to identify and compare the cytokine production profile of activated
versus non-activated HMEC-1. RESULTS: There were significant changes in cytokine
production by HMEC-1 cells following lipopolysaccharide (LPS) treatment and
hypoxic conditioning. Despite this, results from the TEM assay showed no
significant change in the average number of CMSC that migrated through the LPS
activated HMEC-1 layer compared to the untreated control. Furthermore, there was
no significant change in the average number of CMSC that migrated through the
HMEC-1 monolayer when exposed to hypoxic (1% O2), normoxic (8% O2) or hyperoxic
(21% O2) conditions. CONCLUSION: These data suggest that cell functions such as
transendothelial migration can vary between MSC derived from different tissues in
response to the same biological cues.
PMID- 28697980
TI - Consistency of photon emission intensities for efficiency calibration of gamma
ray spectrometers in the energy range from 20keV to 80keV.
AB - The efficiency calibration for different high-purity germanium detectors in the
low-energy range was established by the conventional method, using standard
radioactive sources. The peak shapes were carefully analysed taking account of
natural linewidth, full-energy width at half maximum and scattering.
Complementary information was obtained by Monte Carlo simulation using the
PENELOPE code, after optimization of the geometrical parameters. This was used to
measure photon emission intensities of some low-energy emitting radionuclides,
including 133Ba, and compared to the tabulated values.
PMID- 28697981
TI - Cooperative and competitive contexts do not modify the effect of social intention
on motor action.
AB - In social interactions, the movements performed by others can be used to
anticipate their intention. The present paper investigates whether cooperative vs
competitive contexts influence the kinematics of object-directed motor actions
and whether they modulate the effect of social intention on motor actions. An
"Actor" and a "Partner" participated in a task consisting in displacing a wooden
dowel under time constraint. Before this Main action, the Actor performed a
Preparatory action which consisted in placing the dowel at the center of the
table. Information about who would make the forthcoming Main action was provided
only to the Actor through headphones. Results demonstrate an exaggeration of
spatial and temporal actions' parameters when acting for the Partner, in
cooperative, as well as in competitive context. This finding suggests that the
motor manifestation of social intention is largely determined by non-conscious
implicit processes that seem little influenced by the context of social
interaction.
PMID- 28697982
TI - Prostate Cancer Screening in a New Era of Genetics.
AB - Men who inherit pathogenic germline mutations in BRCA2 and BRCA1 are at increased
risk of developing aggressive prostate cancer, and those with germline mutations
in other DNA repair genes such as ATM, CHEK2, and MSH2/MSH6 may also have
increased risks. Although clinically important, there is lack of specific
guidance regarding management strategies for men at increased risk owing to
germline mutation status or family history of aggressive prostate cancer. We
review prostate cancer genetic risk factors and the ongoing IMPACT
(Identification of Men with a genetic predisposition to ProstAte Cancer: Targeted
screening in BRCA1/2 mutation carriers and controls) screening study. Pending
results of IMPACT and unified guidelines, there are areas of uncertainty and need
for further study. Ongoing and future research will be critical for optimizing
prostate cancer screening approaches for men at the highest risk for aggressive
prostate cancer. In the interim, we propose a practical approach to prostate
cancer screening for men with a germline mutation in a known/suspected moderate
to high-penetrance cancer predisposition gene (eg, BRCA1/2), and/or men with a
first- or second-degree relative with metastatic prostate cancer (regardless of
genetic testing): baseline prostate-specific antigen and digital rectal exam by
experienced providers at age 40 years or 5 years earlier than age of diagnosis of
the youngest first- or second-degree relative with metastatic prostate cancer,
whichever is earlier. Then, based on age, digital rectal exam, and prostate
specific antigen, we suggest consideration of magnetic resonance imaging, biopsy,
and/or continued monitoring.
PMID- 28697983
TI - Lipid and lipoprotein reference values from 133,450 Dutch Lifelines participants:
Age- and gender-specific baseline lipid values and percentiles.
AB - BACKGROUND: Lipids and lipoproteins are recognized as the most important
modifiable risk factors for cardiovascular disease. Although reference values for
the major lipoproteins, low-density lipoprotein cholesterol (LDL-C), high-density
lipoprotein cholesterol, and triglycerides, have been collected in numerous
studies and cohorts, complete contemporary percentile-based reference values are
underreported. OBJECTIVE: We set out to provide such reference lipid data using a
large contemporary population-based cohort study. STUDY DESIGN AND SETTING:
Lifelines is a cross-sectional population-based Dutch cohort study. We analyzed
133,540 adult fasting participants without cardiovascular disease and without
lipid-lowering drug use. Lipid levels were directly measured and selected
percentiles of all lipid parameters were calculated. Friedewald LDL-C estimation
was calculated as well. RESULTS: From 20 till 49 years of age, men were found to
exhibit a steep 64% increase of LDL-C (median +54 mg/dL), while triglyceride
levels increased almost two-fold. In women, LDL-C levels did not change from 18
till 35 years, followed by a steep 42% increase till 59 years (median +42 mg/dL).
In contrast to men, triglycerides were stable in ageing women. Overall,
Friedewald LDL-C levels are lower compared with the direct measurement,
especially with increasing triglyceride levels. CONCLUSIONS: This observational
study highlights striking gender- and age-related differences in plasma lipid
profiles. The given reference ranges of plasma lipids can assist in early
identification of individuals with hypocholesterolemia and hypercholesterolemia,
especially familial hypercholesterolemia. These reference ranges are available
for physicians and patients at www.my-cholesterol.care/.
PMID- 28697984
TI - Potential mechanisms of CD133 in cancer stem cells.
AB - Cancer stem cells (CSCs) have emerged as an underlying cause of cancer relapse
and resistance to treatment. Initially, biomarkers were used to identify and
isolate distinct cell populations. Several CSC markers have been identified from
many types of tumors, and these markers are also being used for isolation and
enrichment of CSCs. Cluster of differentiation CD133 is a well-characterized CSC
marker, and it is involved in tumor cell proliferation, metastasis,
tumorigenesis, and recurrence, as well as chemo- and radio-resistance. However,
the mechanisms involved in CD133-mediated induction of CSC properties have not
yet been elucidated. Here, we introduce and summarize the functions of CD133 in
CSCs and suggest new mechanisms that may be of note in our approach to developing
novel cancer therapies.
PMID- 28697985
TI - Morphological variations of median maxillary labial frenum: A clinical study.
AB - BACKGROUND: Median maxillary labial frenum (MMLF) appears as a fold of mucous
membrane extending from the lining of the mucous membrane of the lips towards the
crest of the alveolar ridge on the labial surface. MMLF can demonstrate certain
variations in their shape, size and position, both among individuals and within
the same individual at different ages. Many clinicians, not being aware of the
normal variations of median maxillary labial frenum misinterpret them as
pathological entities. OBJECTIVES: The objectives of the study were to determine
the prevalence of morphologic variations of MMLF, to classify the morphological
variations of MMLF on the basis of their location on the frenum and to compare
the morphological variations of MMLF among different age groups and genders.
MATERIALS AND METHODS: The study was conducted on 700 males and 700 females of
age 5 to 74 yrs, chosen randomly. They were equally divided on the basis of age
into 7 groups, each group having equal gender distribution. The morphological
variations of MMLF were classified according to Sewerin's classification and the
attachments on the freni were further sub-classified. RESULTS: The commonest type
of frenum was found to be the simple type, whereas bifid frenum was not found at
all. Statistically significant difference was found in proportion of types of
frenum among the different age groups and also in proportion of types of frenum
among the different sites of presence of frenal attachments. No statistically
significant difference was found in proportion of types of frenum in male and
female subjects. CONCLUSION: This study shows that MMLF presents with an array of
morphological variations. These morphological variations may sometimes pose a
complicating factor in maintaining oral hygiene, speech, mastication, esthetics,
denture construction, etc. Hence, appropriate recognition of frenal variations
and subsequent modification of treatment procedures are essential for a
successful outcome of therapy.
PMID- 28697986
TI - Temporalis cysticerci - A diagnostic dilemma and review of literature.
AB - Cysticercosis is a systemic parasitic infestation caused by ingesting the eggs of
the pork tapeworm, Taenia solium. The central nervous system (CNS) is the most
important primary site of infection and disease can present with solitary or
multiple space-occupying lesion. Other organs like subcutaneous tissues, muscles,
heart, liver, lungs, and peritoneum are more frequently affected but
maxillofacial region involvement is rare. The diagnosis of cysticercose is evoked
on US examination and CT scan, but confirmation is only possible by Fine needle
aspiration cytology [FNAC] or histological examination in case of surgical
removal of the oral lesion which can identify the Taenia solium larva. Solitary
intramuscular cysticercosis in maxillofacial region, without involvement of CNS
is a rare entity. We present a rare case of solitary temporalis muscle
involvement without any systemic or neurologic infestation, which presented the
diagnostic and therapeutic dilemma along with review of literature.
PMID- 28697987
TI - Update MRONJ and perspectives of its treatment.
AB - Antiresorptive agents are widely used in catabolic bone diseases. Not only
bisphosphonates but also new drugs like Denosumab may induce osteonecrosis of the
jaw as a side effect. The present review describes the current effect mechanisms
of commonly used antiresorptives, pathogenetic theories for the development of
antiresorptive-related osteonecrosis of the jaw (ARONJ), and potential risk
factors. Furthermore, diagnostic modalities and treatment options as well as new
and innovative strategies are discussed. The major key factor to avoid the
occurrence of ARONJ still remains the implementation of throughout preventive
measures.
PMID- 28697988
TI - The addition of reduced glutathione to cryopreservation media induces changes in
the structure of motile subpopulations of frozen-thawed boar sperm.
AB - : Adding cryopreservation media with reduced glutathione (GSH) has previously
been shown to maintain the motility, membrane integrity and fertilizing ability
of frozen-thawed boar sperm, although the effects of GSH on good (GFE) and poor
freezability (PFE) ejaculates rely upon the intrinsic ejaculate freezability. The
resilience to withstand freeze-thawing procedures has previously been related to
the existence of a specific distribution of motile sperm subpopulations, which
differs between GFE and PFE. Thus, the main aim of this study was to determine
whether the addition of GSH to freezing media has any impact on the distribution
of motile sperm subpopulations in GFE and PFE. With this purpose, 18 GFE and 13
PFE were cryopreserved with or without 2 mM GSH. Sperm quality and motile
subpopulations were evaluated at 30 min and 4 h post-thawing. Three
subpopulations were identified and the percentages of spermatozoa belonging to
the fastest and most linear subpopulation, which was referred as 'SP1', decreased
over post-thawing time. Good freezability ejaculates that were cryopreserved in
the presence of 2 mM exhibited a significantly higher percentage of spermatozoa
belonging to SP1 than the other combinations of treatment and freezability both
at 30 min (mean +/- SEM: GFE-C: 16.6 +/- 0.4; GFE-GSH 27.7 +/- 0.6) and 4 h post
thawing (GFE-C: 7.8 +/- 0.2 vs. GFE-GSH: 16.7 +/- 0.4). In conclusion, the
positive effect of GSH on the motility of frozen-thawed sperm is related to a
specific sperm subpopulation (SP1), which could coincide with the fertile sperm
one.
PMID- 28697989
TI - Sialoendoscopy combined with an internal stent and postoperative massage as a
comprehensive treatment of delayed I131-induced parotitis.
AB - A common complication of radioiodine (I131) treatment of thyroid cancer is
parotitis. Here we describe our clinical experience in treating delayed I131
induced parotitis using sialoendoscopy together with an internal stent and
postoperative massage. In this retrospective cohort study we reviewed 32 patients
who were treated in that way under general anaesthesia between July 2010 and
March 2015. Their age, sex, and the time to development of the parotitis were
collected from the hospital's database. All patients were evaluated using a
visual analogue scale (VAS), sialography, and computed tomography preoperatively.
The analyses of VAS scores were made during postoperative follow-up visits. We
used the paired Student's t test and one-way ANOVA to assess the significance of
differences, and probabilities of < 0.05 were accepted as significant. The mean
(SD) age of the 32 patients was 50 (11) years, and they developed symptoms of
delayed parotitis after a mean (SD) of 12 (11) months. The mean time between
treatment with I131 and sialoendoscopy was 26 (10) months. Ductal stenosis was
the most common sialoendoscopic feature, together with mucous plugs and fibrosis.
Fifty of the 56 ducts were successfully dilated by sialoendoscopy, and VAS scores
significantly decreased from a preoperative 7.3 (1.1) to a postoperative 3.3
(2.1) (p=0.000) during follow-up of 3 - 41 months. Sialoendoscopic interventions
combined with an internal stent and postoperative massage may be optimal
comprehensive treatment for delayed I131-induced parotitis.
PMID- 28697990
TI - Avian antibodies (IgY) against Trypanosoma cruzi: Purification and
characterization studies.
AB - Trypanosoma cruzi is a flagellated protozoan belonging to the Trypanosomatidae
family, the etiologic agent of Chagas disease. Currently, there is neither a
licensed vaccine nor effective treatment, characterizing an unmet clinical need.
The IgY refers to the egg yolk immunoglobulin (Y=yolk) and its production and use
are subjects of many studies due to the diversity of its diagnostic and
therapeutic applications. Several researchers have shown that the use of specific
IgY may prevent and/or control infectious and parasitic diseases. Based on these
evidences, the aim of this study was to immunize chickens with trypomastigotes of
T. cruzi in order to produce highly effective and pure antibodies (IgY), as well
as extract, characterize, quantify, and verify cytotoxic effects of IgY anti-T.
cruzi. After the induction of IgY production by chickens, the eggs were collected
and the IgY was extracted by method of precipitation of polyethylene glycol 6000.
The IgY anti-T. cruzi characterization was performed using polyacrylamide gel
electrophoresis (SDS-PAGE), western-blot and enzyme-linked immunosorbent assay
(ELISA). Moreover, the cytotoxic or proliferative effects of IgY anti-T. cruzi
was verified by MTT assay. The concentration of IgY in yolk was 8.41+/-1.47mg/mL.
The characterization of IgY reveled bands of stained peptides with molecular
weight between 75 and 50kDa and 37 and 25kDa. In the ELISA test was observed that
there was antigen-antibody reaction throughout the sample period. The
concentrations of 1, 5 and 10mg/mL of IgY anti-T. cruzi presented no cytotoxic of
proliferative effects in mononuclear and VERO cells in vitro. The results
indicated that T. cruzi is able to generate a high production of specific
immunoglobulins in chickens, it did not cause damage to the cell membrane and no
proliferative effect.
PMID- 28697991
TI - Carbamazepine effects on pain management and serum IL-6, IL-10 evaluation in
addicted patients undergoing surgery.
AB - Postoperative pain control remains an important issue in the field of surgery.
Assessing and managing patients with acute pain who are addicted to opioids are
often challenging. It has been shown that, addicted patients are less tolerant to
pain. There is limited evidence to guide the management of acute pain in these
patients. Here we studied the effect of preemptive use of carbamazepine on pain
behavior and serum IL-6, IL-10 levels in the addicted patients. 90 male patients
(25-45 years, BMI 20-27), were divided into 3 group of 30 patients: 1- control, 2
addicted, 3- addicted patients receiving carbamazepine 400mg before surgery. The
visual analog pain scale and serum levels of IL-6 and IL-10 were evaluated at
time 0 (before surgery), 1 and 12h postoperatively. Compared with control and
carbamazepine groups, addicted patients exhibited exaggerated pain behavior
before and after surgery, however, postoperatively, a significant increase in
pain behavior was seen in control compared to carbamazepine group. A decrease in
serum IL-10 and an increase in IL-6 concentrations were observed in addicted
patients. In the morphine abuser, a decrease in pain threshold, an increase in IL
6 and a decrease in IL-10 levels were evident compared with non-abuser subjects.
Addition of carbamazepine improved pain sensation and serum IL-6 levels and a
reduction in serum IL-10 level in control patients was paralleled to their
recovery. It seems that, preemptive use of low dose of carbamazepine can improve
postoperative pain and cytokine activities in the addicted patients.
PMID- 28697992
TI - PDE3 inhibition by C-type natriuretic peptide-induced cGMP enhances cAMP-mediated
signaling in both non-failing and failing hearts.
AB - We have previously shown that the natriuretic peptide receptor B (NPR-B) agonist
C-type natriuretic peptide (CNP) enhances cyclic adenosine 3',5'-monophosphate
(cAMP)-mediated signaling in failing hearts, through cyclic guanosine 3',5'
monophosphate (cGMP)-mediated phosphodiesterase (PDE) 3 inhibition. As several
signaling pathways are importantly changed in failing hearts, it could not be
taken for granted that this crosstalk would be the same in non-failing hearts.
Thus, we wanted to clarify to which extent this effect of CNP occurred also in
non-failing hearts. Inotropic and lusitropic responses were measured in muscle
strips and cGMP levels, localized cAMP levels, cAMP-PDE activity and mRNA levels
were analyzed in isolated cardiomyocytes from left ventricles of non-failing and
failing rat hearts. CNP increased cGMP and enhanced beta1- and beta2-adrenoceptor
mediated inotropic and beta1-adrenoceptor-mediated lusitropic responses, in non
failing and failing hearts. The NPR-A agonist brain natriuretic peptide (BNP)
increased cGMP, but did not affect inotropic or lusitropic responses, indicating
different compartmentation of cGMP from the two natriuretic peptide receptors.
cAMP-PDE activity of PDE3 was concentration-dependently inhibited by cGMP with
the same potency and to the same extent in non-failing and failing
cardiomyocytes. CNP enhanced beta1-adrenoceptor-induced cAMP increase in living
cardiomyocytes in the absence, but not in the presence of a PDE3 inhibitor
indicating involvement of PDE3. In summary, CNP sensitizes cAMP-mediated
signaling in non-failing as in failing hearts, via NPR-B-mediated increase of
cGMP that inhibits the cAMP-PDE activity of PDE3.
PMID- 28697993
TI - Dipeptidyl peptidase IV inhibitors as novel regulators of vascular disease.
AB - Dipeptidyl peptidase IV (DPP-IV) has been revealed as an adipokine with potential
relevance in cardiovascular disease (CVD), while clinically used DPP-IV
inhibitors have demonstrated beneficial cardiovascular effects in several
experimental studies. Perivascular adipose tissue (PVAT) is a unique adipose
tissue depot in close anatomical proximity and bidirectional functional
interaction with the vascular wall, which is a source of DPP-IV and its biology
may be influenced by DPP-IV inhibition. Recently, DPP-IV inhibition has been
associated with decreased local inflammation and oxidative stress both in the
vascular wall and the PVAT, potentially regulating atherogenesis progression in
vivo. DPP-IV inhibition may thus be a promising target in cardiovascular disease.
However, the exact pleiotropic mechanisms that underlie the cardiovascular
effects of DPP-IV inhibition need to be clarified, while the in vivo benefit of
DPP-IV inhibition in humans remains unclear.
PMID- 28697994
TI - Molecular epidemiology of Dientamoeba fragilis.
AB - The flagellated protozoan Dientamoeba fragilis is one of the most commonly
diagnosed parasite of the human gut, with a global distribution. Nevertheless,
essential aspects of its biology remain incompletely understood or controversial,
most notably life cycle, host range, transmission routes and the ability to cause
disease. Molecular epidemiologic studies are also scarce, and limited by the lack
of informative genotyping tools. To date, two D. fragilis genotypes (1 and 2) are
recognized, with a strong predominance of genotype 1 in both humans and few
animal hosts. Recent studies have shown that a very low level of genetic
variability characterizes parasite isolates collected in various geographic areas
and from both symptomatic and asymptomatic cases. This has raised the hypothesis
D. fragilis may be a clonal organism. The recent availability of transcriptome
data should greatly assist the development of markers useful to understand
genetic diversity of D. fragilis at the population level.
PMID- 28697995
TI - Evaluation of toxicity studies of flavonoid fraction of Lithocarpus polystachyus
Rehd in rodents.
AB - The aim of the study was to evaluate the safety of flavonoid fraction of
Lithocarpus polystachyus Rehd (Sweet Tea-F, ST-F) in mice and rats through acute
and sub-chronic toxicity studies respectively. For acute toxicity study, a single
dose of 5000 mg/kg of ST-F was given orally to healthy KM mice. The mice were
observed mortality and toxic symptoms for 24 h, then once a day up to 14 days. In
the sub-chronic toxicity study, ST-F was administered orally at doses of 0, 70,
140, 560 mg/kg/day to rats for 26 weeks. Body weight and food intake were
recorded weekly. Hematological, biochemical, coagulation and organ parameters
were analyzed at the end of 26 weeks administration. Vital organs were evaluated
by histopathology. In the acute toxicity study, ST-F caused neither significant
toxic symptoms, nor mortality in mice. In sub-chronic toxicity study, daily oral
administration of ST-F at the dose of 70 mg/kg resulted in a significant increase
(P < 0.05) in the relative body weight at the 10-week, and the same situation
brought at the dose of 140 mg/kg/day at the 22-week. Hematological and
biochemical showed significant changes (P < 0.01 or P < 0.05) in WBC, GLU, ALP,
AST and serum electrolytes levels at the dose of 560 mg/kg/day. The amount of RBC
decreased significantly (P < 0.05) while the content of PLT slightly increased (P
< 0.05) at the dose of 140 mg/kg/day. In additional, no obvious histological
changes were observed in vital organs of ST-F treated animals compared to control
group. The ST-F may be exit slight side effects at the dose of 560 mg/kg/day in
rats. Thus, the overall results show that the no-observed adverse effect level
(NOAEL) of ST-F was considered to be 140 mg/kg for male SD rats.
PMID- 28697996
TI - S-25-hydroxyvitamin D and C3-epimers in pregnancy and infancy: An Odense Child
Cohort study.
AB - BACKGROUND: Analysis of serum 25-hydroxyvitamin D (s-25(OH)D) may be complicated
by the less active or in-active vitamin D metabolite C3-epi-25(OH)D3 (C3-epimer).
We aimed to explore the relationship between s-C3-epimer and s-25(OH)D and other
determinants and describe the longitudinal course of the C3-epimer fraction in
paired mother-child samples. METHOD: S-25(OH)D and s-C3-epimer were estimated by
liquid chromatography mass spectrometry in 290 mother-infant pairs from the
population-based Odense Child Cohort. Longitudinal analyses were feasible in two
subcohorts; B) early and late pregnancy, cord, three and 18months (n=132); and C)
early and late pregnancy, delivery and cord (n=105). RESULTS: Mean s-25(OH)D was
50.6-110.4nmol/L at the six time points. The mean C3-epimer fraction was 10.1% at
three months, 1.1%-3.0% at the other time points. In multivariate analyses, the s
C3-epimer correlated with s-25(OH)D (all time points, p<0.001), and season,
maternal and infant age and maternal vitamin D supplementation at some time
points. The C3-epimer fraction fluctuated between adjacent time points. By
cosinor analyses, a season-dependent sinusoidal pattern for s-25(OH)D and C3
epimer fraction was found and changes between adjacent time points depended on
season (p<0.007 or trend). In early infancy, subtraction of the C3-epi-25(OH)D3
from total s-25(OH)D resulted in reclassification of 8% of the children by use of
the 75nmol/L cut off for s-25(OH)D. CONLCUSION: The s-C3-epimer was independently
correlated to s-25(OH)D, season, maternal vitamin D supplementation, maternal and
infant age. The C3-epimer fraction was only of clinical importance in early
infancy, where it could lead to misclassification of the vitamin D status.
PMID- 28697997
TI - The impact of parental history of type 2 diabetes on hyperinsulinemia and insulin
resistance in subjects from central Mexico.
AB - AIMS: Hyperinsulinemia and insulin resistance are both associated with the
development of Type 2 Diabetes and other pathologies; however, the influence of
parental history of Type 2 diabetes (PH-T2D) has yet to be investigated.
Therefore, this study was conducted to determine the effect of PH-T2D has on the
risk of developing hyperinsulinemia and IR. MATERIALS AND METHODS: 1092 subjects
(703 non-pregnant females and 389 males) were enrolled for a cross-sectional
study. Clinical and biochemical parameters were collected. Subjects were
allocated according to their PH-T2D: no parents, one parent, or both parents.
Insulin resistance was calculated using the HOMA1 equation (HOMA1-IR). Logistic
regression was used to determine the association (odds ratio) between PH-T2D and
hyperinsulinemia or insulin resistance. RESULTS: Increasing degrees of PH-T2D
were associated with significant increases in fasting plasma glucose, insulin,
and HOMA1-IR (p <0.05). Subjects having one or both parents were associated with
an increase risk of developing hyperinsulinemia (odds ratio=1.53, 95%CI: 1.12
2.09, and odds ratio=1.92, 95%CI: 1.21-3.06, respectively) and insulin resistance
(odds ratio=1.47, 95%CI: 1.08-2.00 and odds ratio=1.77, 95%CI: 1.09-2.87,
respectively), when adjusting for age, sex, BMI, fasting plasma glucose, and
triglycerides. CONCLUSION: The presences of PH-T2D significantly increased the
risk of developing hyperinsulinemia and insulin resistance.
PMID- 28697998
TI - Neural and behavioural correlates of autobiographical memory retrieval in
patients with major depressive disorder and a history of trauma exposure.
AB - Alterations in autobiographical memory (AM) performance have been identified in
major depressive disorder (MDD) and in trauma-related disorders, however, the
neural and behavioural correlates of AM retrieval in patients with MDD and a co
morbid history of trauma remain unexplored. Here, we used behavioural and
neuroimaging techniques to investigate AM in this patient group and in matched
healthy comparison subjects (HCs). Twenty patients with MDD and trauma exposure
and 20 HCs underwent fMRI scanning while recalling positive, negative, and
neutral events. Participants were subsequently administered the Autobiographical
Interview (Levine et al., 2002), allowing for separation of episodic and non
episodic details of memories. Key clinical variables, including illness severity,
dissociative (e.g., depersonalization, derealization) symptoms, and history of
parental bonding, were assessed. Compared to controls, patients showed reduced
activation in the left parahippocampus and left anterior insula during retrieval
of positive memories. Among patients, greater specificity of positive AM recall
on the Autobiographical Interview was related to reduced activation of the left
anterior insula during retrieval of positive memories. Moreover, increased left
parahippocampal activation during negative memory recall was related to
heightened levels of paternal care among the patient group. Taken together, these
findings point towards potential alterations in key neural processes (e.g.,
episodic vividness and embodiment) associated with AM retrieval among MDD
patients with a history of co-morbid trauma exposure. These alterations appear
unrelated to illness severity, but instead are associated with parental bonding.
PMID- 28697999
TI - The protective role of TET2 in erythroid iron homeostasis against oxidative
stress and erythropoiesis.
AB - Although previous studies suggested that stress erythropoiesis and iron
metabolism regulate each other to increase iron availability for hemoglobin
synthesis, the molecular bases determining its different traits remain elusive.
In addition, global DNA demethylation has been reported during mouse
erythropoiesis in vivo. However, the understanding of iron-related genes through
DNA demethylation under stress erythropoiesis is largely unknown. In the current
study, we found disordered iron homeostasis and misregulated hepcidin-ferroportin
axis under stress erythropoiesis. Interestingly, global 5hmC content and TET2
expression were significantly induced by oxidative stress, whereas antioxidant
had the opposite's effect. Mechanistic investigation manifested that TET2
mediated DNA demethylation promotes the expression of ferroportin and
erythroferrone against oxidative stress. Besides, the expression of NRF2 was
significantly increased by TET2-mediated DNA demethylation during stress
erythropoiesis. Elevated NRF2 expression could also modulate the activation of
ferroportin and erythroferrone through a canonical antioxidant response element
within its promoter. These direct and indirect pathways of TET2 synergistically
cooperated to mediating iron metabolism during stress erythropoiesis. Our work
revealed a critical role of TET2-mediated DNA demethylation against oxidative
stress, and provided the molecular mechanisms underlying the epigenetic
regulation of iron homeostasis in response to stress erythropoiesis.
PMID- 28698000
TI - Topical diltiazem ointment in post-hemorrhoidectomy pain relief: A meta-analysis
of randomized controlled trials.
AB - BACKGROUND: Hemorrhoidectomy is commonly associated with postoperative pain.
Calcium channel blockers are known to cause relaxation of gastrointestinal smooth
muscle and oral diltiazem has also been shown to reduce the resting anal
pressure. OBJECTIVE: We attempted to analyze efficacy and side effects of topical
diltiazem oint. in post-operative pain control. METHODS: This is a meta-analysis
of patients who underwent hemorrhoidectomy using topical diltiazem oint. versus
placebo (Vaseline) for pain control. Patients with third or fourth degree
hemorrhoids undergoing traditional hemorrhoidectomy were included. Procedures
took place in the colorectal division of a hospital in 5 countries. Five
randomized control trials (RCTs) published between 2005 and 2016 including 227
patients were included our meta-analysis (Diltiazem (calcium channel block) group
= 137; Placebo (Vaseline) group = 90). Pain assessment was performed using a
standardized Visual Analogue Scale. Any side effects of surgery or medication
use, which were noted by the patient or the surgeon, also were recorded. RESULTS:
A total of 227 patients were included in the meta-analysis. The results revealed
that Diltiazem ointment was statistically significant in reducing pain within 48
h, at 72 h, and more than 96 h after operation compared to the placebo group.
Regarding overall complications (including headache), there was no statistical
significance between diltiazem and placebo group. CONCLUSIONS: Topical
application of diltiazem effectively relieves pain after hemorrhoidectomy with
minimal side effects. Further large studies are needed to substantiate its value
in clinical practice.
PMID- 28698001
TI - Biolayer interferometry predicts ELISA performance of monoclonal antibody pairs
for Plasmodium falciparum histidine-rich protein 2.
AB - Predicting antibody pair performance in a sandwich format streamlines development
of antibody-based diagnostics and laboratory research tools, such as enzyme
linked immunosorbent assays (ELISAs) and lateral flow immunoassays (LFAs). We
have evaluated panels of monoclonal antibodies against the malarial parasite
biomarker Plasmodium falciparum histidine rich protein 2 (HRP2), including 9 new
monoclonal antibodies, using biolayer interferometry (BLI) and screened antibody
pairs in a checkerboard ELISA. This study showed BLI predicts antibody pair ELISA
performance for HRP2. Pairs that included capture antibodies with low off-rate
constants and detection antibodies with high on-rate constants performed best in
an ELISA format.
PMID- 28698003
TI - Addenda.
PMID- 28698002
TI - The flavonol-enriched Cistus albidus chloroform extract possesses in vivo anti
inflammatory and anti-nociceptive activity.
AB - ETHNOPHARMACOLOGICAL RELEVANCE: Cistus albidus L. (Cistaceae) has been
traditionally used to treat various inflammatory diseases, but no systematic
studies on the anti-inflammatory and anti-nociceptive actions of C. albidus and
its putative mechanism have been reported. We aimed to explore the anti
inflammatory and anti-nociceptive effects of this plant and to characterize its
polyphenolic composition by liquid chromatography coupled to mass spectrometry
(MS). MATERIALS AND METHODS: A chloroform extract derived from C. albidus leaves
was obtained by solid-liquid and liquid-liquid extraction. The tail immersion
test and acetic-acid-induced writhing test were used to evaluate the anti
nociceptive action, while the experimental lambda-carrageenan-induced paw edema
model was used to test the anti-inflammatory action. Changes in cyclooxygenase
(COX)-2 and inducible nitric oxide synthase (iNOS) expression, as well as the
role of mitogen-activated protein kinases (MAPKs) and the nuclear transcription
factor kappa B (NF-kB) signaling pathways on lipopolysaccharide (LPS)-stimulated
murine peritoneal macrophages were analyzed by western blotting. HPLC with diode
array detection coupled to tandem mass spectrometry detection with electrospray
ionization (HPLC-DAD-ESI-MS/MS) was performed to determine the phytochemical
profile of the extract. RESULTS: Significant anti-nociceptive activity was
observed both in the tail immersion (59.63% reduction at 120min) and in the
acetic acid (65.94% inhibition) tests at 100mg/kg. The extract (50mg/kg)
exhibited a substantial reduction in paw edema (51.6%) and significantly
inhibited nitrite generation (72.62%) without affecting cell viability of LPS
stimulated murine peritoneal macrophages. These results were concomitant with a
down-regulation of the pro-inflammatory enzymes COX-2 and iNOS in extract-treated
macrophages and a decrease in p38 MAPK phosphorylation. HPLC-DAD-ESI-MS/MS
analysis revealed that flavonols such as kaempferol and quercetin derivatives
were potentially responsible for such effects. CONCLUSION: These results support
the widespread use of C. albidus in popular medicine and indicate that this plant
has therapeutic potential with analgesic and anti-inflammatory properties based
on the presence of flavonol derivatives.
PMID- 28698004
TI - The effect of radiotherapy on fat content and fatty acids in myxoid liposarcomas
quantified by MRI.
AB - BACKGROUND: Myxoid liposarcomas are highly radiosensitive. Consequently
radiotherapy is often used pre-operatively to reduce tumor volume and lessen the
post-operative deficit. In soft-tissue sarcomas therapy response is mainly
evaluated using magnetic resonance imaging (MRI) and the fundamental criterion
for a positive response is decreased tumor size. In myxoid liposarcomas an
increased fat content is also known to occur as a response to radiotherapy.
OBJECTIVE: To highlight the difficulties of MRI for therapy response evaluation
in irradiated myxoid liposarcomas, by using MRI Dixon techniques enabling
objective quantification of proton density fat fraction (%) and the number of
double bonds (ndb; unsaturation degree) of fatty acids. Secondly, to compare
quantitative fat fraction measurements versus visual grading of fat content on T1
weighted images. CASE DESCRIPTIONS: Prior to surgery, two patients with myxoid
liposarcoma were treated with 50Gy. Following radiotherapy, both tumors on MRI
showed reduced size, elevated fat fraction and transformed fat fraction
histograms with diverse changes of ndb, while histopathological specimens showed
discordant treatment effects; one case having good response and the other having
poor response. CONCLUSIONS: A decrease in tumor size and increase in fat content
on MRI cannot be interpreted as positive therapy response in radiotherapy of
myxoid liposarcomas. Our data also give further supporting evidence that
differentiation and maturation of tumor cells is the cause for the lipoma-like
areas seen after radiotherapy. Finally, quantitative MRI Dixon techniques are
preferable to visual grading for estimating the fat content in lipomatous tumors.
PMID- 28698005
TI - Meckel's diverticulum in the adult.
AB - Meckel's diverticulum (MD) is the most common gastro-intestinal congenital
malformation (approximately 2% in the overall population). The lifetime risk of
related complications is estimated at 4%. These include gastro-intestinal
bleeding, obstruction or diverticular inflammation. Diagnosis is difficult and
rarely made, and imaging, especially in the case of complicated disease, is often
not helpful; however exploratory laparoscopy is an important diagnostic tool. The
probability of onset of complication decreases with age, and the diagnosis of MD
in the adult is therefore often incidental. Resection is indicated in case of
complications but remains debatable when MD is found incidentally. According to
an analysis of large series in the literature, surgery is not indicated in the
absence of risk factors for complications: these include male gender, age younger
than 40, diverticulum longer than two centimetres and the presence of
macroscopically mucosal alteration noted at surgery. Resection followed by
anastomosis seems preferable to wedge resection or tangential mechanical stapling
because of the risk of leaving behind abnormal heterotopic mucosa.
PMID- 28698006
TI - Identification of TRADD as a potential biomarker in human uterine leiomyoma
through iTRAQ based proteomic profiling.
AB - Recurrent and refractory leiomyoma of uterus is one of the most common diseases
in women of reproductive age. Despite its benign nature, uterine leiomyoma has
presented an extremely deleterious impact on public health. The etiology of
uterine leiomyoma remains unclear and clinical management remains suboptimal,
leaving radical hysterectomy the only effective approach. Delineating the
molecular mechanism underlying the leiomyoma initiation and progression remains
an unmet clinical need. To screen proteins that were differentially expressed in
uterine leiomyoma versus normal myometrium, we examined proteomic profile by
isobaric tag for relative and absolute quantitation (iTRAQ) labeling coupled with
liquid chromatography - tandem mass spectrometry (LC-MS/MS). 72 proteins have
been identified as differentially expressed in uterine leiomyoma, including the
downregulation of TRADD (tumor necrosis factor receptor type 1-associated DEATH
domain protein), which dominates the dysfunctional extrinsic apoptosis pathway
and deregulated inflammatory responses. The reduction of TRADD was further
validated by Western blot and immunohistochemistry in independent sample cohorts.
Our data thus suggest potential biological significance of TRADD mediated
inflammatory response in the development of uterine leiomyoma.
PMID- 28698007
TI - Solving fatigue-related problems with cardiac arrest survivors living in the
community.
AB - AIM: The aim was to describe fatigue-related problems reported by post-cardiac
arrest adults with chronic fatigue and energy conservation strategies generated
using an Energy Conservation plus Problem Solving Therapy intervention. METHODS:
Following an introduction to the intervention process outlined in a Participant
Workbook, participants engaged in the telephone intervention by identifying one
to two fatigue-related problems. They then brainstormed with the interventionist
to identify potential strategies to reduce fatigue, tested them, and either
modified the strategies or moved to the next problem over three to five sessions.
RESULTS: Eighteen cardiac arrest survivors with chronic fatigue identified
instrumental activities of daily living and leisure activities as fatigue-related
activities more frequently than basic activities of daily living. Energy
Conservation strategies used most frequently were: plan ahead, pace yourself,
delegate to others, and simplify the task. CONCLUSION: Post-cardiac arrest adults
living in the community with chronic fatigue can return to previous daily
activities by using energy conservation strategies such as planning ahead, pacing
tasks, delegating tasks, and simplifying tasks.
PMID- 28698008
TI - Prognostic significance of tumor-associated macrophages in ovarian cancer: A meta
analysis.
AB - OBJECTIVE: The role of tumor-associated macrophages (TAMs) in tumor
microenvironment remains controversial due to the two different polarized subsets
of TAMs. Here, we performed a meta-analysis to evaluate the correlation between
subpopulations of TAMs and clinical outcomes in patients with ovarian cancer.
METHODS: A comprehensive search in PUBMED/Medline and EMBASE databases was
performed. The association between TAMs and patient prognosis of ovarian cancer
was estimated with hazard ratios (HRs) and their corresponding 95% confidence
intervals (95% CIs) using a random-effect model. Additionally, sensitivity
analysis and Begg's test were conducted. RESULTS: Nine studies including 794
patients were enrolled in the meta-analysis. The results showed that higher M1/M2
ratio in tumor tissues was associated with a favorable overall survival (OS)
(HR=0.449, 95% CI=0.283-0.712, P=0.001). Elevated intra-islet M1/M2 TAMs ratio
showed a positive correlation for OS (HR=0.510, 95% CI=0.264-0.986, P=0.045). No
significant relation was observed between OS and CD68+ TAMs (HR=0.99, 95% CI=0.88
1.11, P=0.859), CD163+ TAMs (HR=1.04, 95% CI=0.92-1.16, P=0.544) or CD163+/CD68+
TAMs ratio (HR=1.628, 95% CI=0.529-5.008, P=0.395). Worse progression-free
survival (PFS) was associated with high density of CD163+ TAMs (HR=2.157, 95%
CI=1.406-3.312, P=0.000) and higher ratio of CD163+/CD68+ TAMs (HR=3.223, 95%
CI=1.805-5.755, P=0.000). Elevated M1/M2 TAMs ratio predicted better PFS of
ovarian cancer (HR=0.490, 95% CI=0.270-0.890, P=0.019). Furthermore, high density
of CD163+ and CD68+ TAMs was observed in ovarian cancer with advanced TNM stage.
CONCLUSION: In our study, it was revealed that CD163+ TAMs infiltration was
associated with poor prognosis of ovarian cancer and high M1/M2 macrophages ratio
in tumor tissues predicted better prognosis.
PMID- 28698009
TI - A randomised, open-label, phase 2 study of the IDO1 inhibitor epacadostat
(INCB024360) versus tamoxifen as therapy for biochemically recurrent (CA-125
relapse)-only epithelial ovarian cancer, primary peritoneal carcinoma, or
fallopian tube cancer.
AB - OBJECTIVE: Indoleamine 2,3-dioxygenase-1 (IDO1) is a key regulator of immune
tolerance in ovarian cancer. This study investigated efficacy and safety of the
IDO1 enzyme inhibitor epacadostat versus tamoxifen in patients with biochemical
only recurrence (CA-125 elevation) following complete remission after first-line
chemotherapy for advanced epithelial ovarian, primary peritoneal, or fallopian
tube cancer. METHODS: In this open-label, phase 2 study (NCT01685255), patients
were randomised 1:1 to epacadostat 600mg or tamoxifen 20mg twice daily for
successive 28-day cycles and stratified by time since completion of first-line
chemotherapy to first CA-125 elevation (3 to <12 or >=12months). The primary
endpoint was investigator-assessed progression-free survival (PFS; RECIST v1.1).
Secondary endpoints included CA-125 response (Gynecologic Cancer InterGroup
criteria), overall survival, safety, and tolerability. RESULTS: The study was
terminated primarily due to slow accrual and lack of evidence of superiority.
Median PFS was 3.75months for epacadostat (n=22) versus 5.56months for tamoxifen
(n=20; HR, 1.34 [95% CI, 0.58-3.14]; P=0.54). Of evaluable patients, 1 (5.0%)
epacadostat and 3 (15.8%) tamoxifen patients had confirmed CA-125 responses. The
most common treatment-emergent adverse event was fatigue (epacadostat, 36.4%;
tamoxifen, 40.0%). Immune-related adverse events, observed with epacadostat only,
were primarily rash (18.2%) and pruritus (9.1%). Epacadostat
pharmacokinetics/pharmacodynamics were consistent with its known mechanism of
action. IDO1 expression was observed in 94% of archival tumour samples.
CONCLUSIONS: This first report of immunotherapy evaluation in biochemical-only
relapse ovarian cancer and of IDO1 inhibitor monotherapy in ovarian cancer found
no significant difference in efficacy between epacadostat and tamoxifen.
Epacadostat was generally well tolerated.
PMID- 28698010
TI - Compliance with research standards within gynecologic oncology fellowship: A
Gynecologic Oncology Fellowship Research Network (GOFRN) study.
AB - OBJECTIVES: Participation in clinical and basic science research is emphasized in
gynecologic oncology training. We sought to identify trends in adherence to
expected research practices and reasons for non-adherence among gynecologic
oncology fellows. METHODS: An anonymous 31-question online survey assessing
academic behaviors, including IRB compliance, authorship assignment, data
sharing, and potential barriers to non-adherence was distributed to all SGO
gynecologic oncology fellow members in July 2016. Descriptive statistics and
univariate analyses were performed. RESULTS: Of 190 members, 35.3% (n=67)
responded. 73% (n=49) of respondents reported personal non-compliance and 79.1%
(n=53) reported having witnessed others being non-complaint with at least one
expected research practice. Areas of compliance failure included changing a
research question without appropriate IRB amendment (20%; n=14), conducting
research under a nonspecific IRB (13.9%; n=9), and performing research without
IRB approval (6.1%; n=4). Longer institutional time for IRB approval was
significantly associated with IRB non-adherence (p<0.05). First year fellows were
more likely to use a nonspecific IRB (p=0.04) or expand a question without
amending the IRB (p=0.04). When asked about storage of protected health
information (PHI) for research, 53% reported non-secure storage with 17.1% (n=6)
having done so for >1000 patients. Thirty respondents (45.5%) assigned authorship
to someone who failed to meet ICMJE criteria and twelve (18.5%) accepted
authorship without meeting ICMJE criteria. Most commonly cited reasons for non
adherence were: cumbersome IRB processes (80.3%), pressure from senior authors
(78.8%), fear of someone else publishing first, (74.2%) and lack of support
navigating appropriate research practices (71.2%). CONCLUSIONS: Fellow non
compliance with expected research practices is high, particularly with regards to
secure storage of PHI and appropriate authorship assignment. Time-consuming and
cumbersome IRB procedures, perceived pressure from senior authors, and lack of
research support contribute to non-adherence. Further support and education of
gynecologic oncology fellows is needed in order to help address these barriers.
PMID- 28698011
TI - Clinical and morphological manifestations of aniridia-associated keratopathy on
anterior segment optical coherence tomography and in vivo confocal microscopy.
AB - PURPOSE: The study aimed to evaluate clinical and morphological changes in the
limbal palisades of Vogt (POV) at different stages of aniridia-associated
keratopathy (AAK) and to assess possible utility of anterior segment optical
coherence tomography (AS-OCT) for the visualization of limbal progenitor
structures as it correlates to laser scanning confocal microscopy (LSCM) data.
METHODS: The study involved 32 patients (59 eyes) with congenital aniridia. AAK
stage was defined based on biomicroscopy. Assessment of limbal zone and detection
of POVs in identical areas was performed by LSCM (HRT3) and AS-OCT (RTVue XR
Avanti) using 3D Cornea (En Face mode) and Cornea Cross Line protocols. RESULTS:
Intact and changed POVs were found in 8/8 stage 0 eyes, in 1/21 stage I and 2/13
stage II eyes. Spearman's correlation coefficient in assessing the consistency of
the POV diagnostic results by LSCM and AS-OCT for the inferior limbus was rS =
0.85 (P < 0.05), for the superior limbus - rS = 0.53 (P < 0.05). AS-OCT was less
sensitive for detection of partially present POVs in superior limbus. The
negative correlation between AAK stage and POV preservation was determined (rS =
0.5, P < 0.05). There was no correlation between AAK stage and patient age (rS =
0.235, P = 0.209). Three patients with PAX6 3' deletion showed stage 0 AAK with
intact or slightly disturbed POVs morphology and transparent cornea. CONCLUSION:
AS-OCT may be an additional diagnostic tool for POV visualization in vivo in
aniridic patients. Its diagnostic accuracy is subject to selection of anatomic
region, nystagmus and the degree of POV degradation.
PMID- 28698012
TI - The relation between craving and binge eating: Integrating neuroimaging and
ecological momentary assessment.
AB - The role of craving in binge eating characteristic of bulimia nervosa (BN) is
inconclusive. A network of regions associated with cue reactivity to food and
substances has been identified, comprised of the amygdala, orbitofrontal cortex,
insula, and striatum. The goal of this study was to examine individual
differences in BOLD response in this appetitive network as moderators of the
relationship between craving and binging in the natural environment in women with
BN. Women with BN (N = 16) completed a baseline measure of craving and a fMRI
scan, where they viewed neutral cues and food cues. After each run, craving for
food was assessed. Participants then completed an ecological momentary assessment
six times a day via smart phone and recorded binge eating and craving.
Participants exhibited significantly increased BOLD response in the left amygdala
in response to food cues compared to neutral cues. However, individual
differences in BOLD response were not correlated with self-report craving
throughout the scan. The relationship between craving and binging in everyday
life was moderated by individual differences in activation in the caudate,
insula, and amygdala. Women with greater activation in these regions demonstrated
significant increases in craving prior to binge eating. Those who did not exhibit
increases in activation did not exhibit increases in craving prior to binge
eating in the natural environment. Craving may not underlie binge eating for all
individuals with BN. However, these results indicate that neural response to food
cues may affect individual differences in the daily experience of craving and
binge eating.
PMID- 28698013
TI - Links between early child maltreatment, mental disorders, and cortisol secretion
anomalies.
AB - Early child maltreatment has been widely associated with the development of
mental disorders in both childhood and adulthood. However, such association
cannot be systematically established, as only few factors are observed regularly,
such as high prevalence of comorbidities and externalized disorders. Similarly,
the association between early abuse and cortisol secretion anomalies has been
well-documented. Whereas early hypercortisolism followed by hypocortisolism was
often described, the results proved inconsistent and at times contradictory. The
physiopathological mechanisms are quite complex and varied, including mixed
neurotoxicity and stress response anomalies, linked to circadian rhythm
disturbances. One of the difficulties inherent to research on this topic is to
better define maltreatment in childhood. Studying children's groups at risk of
maltreatment, such as children followed by juvenile justice or in child welfare
systems, could be a very good tool, provided that social, judiciary, and mental
health professionals are able to work together and implement common research
objectives.
PMID- 28698014
TI - Adenoviral-expressed recombinant granulocyte monocyte colony-stimulating factor
(GM-CSF) enhances protective immunity induced by inactivated Newcastle Disease
Virus (NDV) vaccine.
AB - Although vaccination has been hugely successful in protecting birds against
infection by the New castle disease virus (NDV), newly-emerged highly virulent
strains have been found to overcome established immune protection and threaten
the poultry industry. The need to improve the immunization efficacy is,
therefore, urgent. Here, we tested the potential immunostimulatory adjuvant
activity of the adenoviral-expressed recombinant chicken granulocyte monocyte
colony stimulating factor (rchGM-CSF) in an inactivated Newcastle Disease Virus
(NDV) vaccine. 126 commercial layer chicks, divided into six groups, were first
vaccinated at day 7, followed by a subsequent boost and later an intramuscular
challenge at day 21 and 35 respectively. rchGM-CSF expressed by adenovirus raised
NDV-specific hemagglutinin-inhibition (HI) titers from 10 to 12 (log2) and
significantly upregulated the production of interferon alpha/beta/gamma (IFN
alpha/beta/gamma), interleukin-4 (IL-4) and major histocompatibility complex II
(MHC-II) in spleens. Crucially, chicks inoculated with the inactivated NDV
vaccine plus the rchGM-CSF adjuvant displayed only mild clinical signs, lower
tissue viral loads, fewer tissue lesions, and decreased mortality and viral
shedding than those in the group immunized with the vaccine alone. Our present
work has demonstrated that chicken GM-CSF may act as an enhancer in the
orchestration of host immune responses induced by the inactivated NDV vaccine.
The molecule, expressed by an adenovirus, has the potential to be used as an
immune adjuvant to improve protection by NDV vaccination.
PMID- 28698015
TI - Genetic polymorphism in three ethnic groups in the Chongqing region of China.
PMID- 28698016
TI - The timing and importance of motor skills course in knee arthroscopy training.
AB - OBJECTIVES: The aim of this prospective study is to evaluate the impact of the
simulation training program in learning duration of arthroscopic motor skills.
Furthermore, we investigated the difference between junior and experienced
residents in the improvement of arthroscopic motor skills duration. METHODS: We
established 2 study groups according to participants' year of experience in
orthopedic residency with junior group residents with three years or less than
three years experience as group 1 and experienced group with over 3 years of
experience as group 2. We calculated duration change of motor skill test results
for each participant before and after the course. The tools used were; auto
scoring mirror tracer(ASMT), 0'Conner the tweezer dexterity test(OCTDT), etch-a
sketch with overlay(ESOT), purdue the pegboard test(PPT), two-arm coordination
test(TACT) and grooved pegboard test(GPT) which were all produced by Lafayette
firm. These instruments were used to practice and measure the basic motor skills.
RESULTS: All post-course test durations for participants decreased significantly
when compared to pre-course. We calculated percentage change of motor skill test
results for each participant before and after the course. All motor skill test
percentage changes were similar between two groups. In comparison of participants
according to their experiences, results revealed that there was no difference in
test results of experienced and junior surgeons. Both groups had provided equal
improvement in terms of motor skills. CONLUSION: As our results revealed,
residents will be able to act with a strong motivation to learn applications
through basic arthroscopic information gained in early period of orthopedic
training and will make more successful applications of real patients.
PMID- 28698017
TI - Stepwise introduction of laparoscopic liver surgery: validation of guideline
recommendations.
AB - BACKGROUND: Uncontrolled introduction of laparoscopic liver surgery (LLS) could
compromise postoperative outcomes. A stepwise introduction of LLS combined with
structured training is advised. This study aimed to evaluate the impact of such a
stepwise introduction. METHODS: A retrospective, single-center case series
assessing short term outcomes of all consecutive LLS in the period November 2006
January 2017. The technique was implemented in a stepwise fashion. To evaluate
the impact of this stepwise approach combined with structured training, outcomes
of LLS before and after a laparoscopic HPB fellowship were compared. RESULTS: A
total of 135 laparoscopic resections were performed. Overall conversion rate was
4% (n = 5), clinically relevant complication rate 13% (n = 18) and mortality 0.7%
(n = 1). A significant increase in patients with major LLS, multiple liver
resections, previous abdominal surgery, malignancies and lesions located in
posterior segments was observed after the fellowship as well as a decrease in the
use of hand-assistance. Increasing complexity in the post fellowship period was
reflected by an increase in operating times, but without comprising other
surgical outcomes. CONCLUSION: A stepwise introduction of LLS combined with
structured training reduced the clinical impact of the learning curve, thereby
confirming guideline recommendations.
PMID- 28698018
TI - Carrying pieces of information in organocatalytic bytes: Semiopoiesis-A new
theory of life and its origins.
AB - Living beings have been classically described as autopoietic machines: chemical
systems, which maintain a reproducible steady state by producing their components
and boundaries. On the other hand, very simple autopoietic micelles have been
produced in laboratory. They consist in micelles able to catalyse the production
of their own surfactants. However is very clear that these autopoietic systems
are unable to evolve. In this way, these autopoietic micelles cannot be
associated to living organisms, which are always linked by evolutionary
relationships. Here I claim that living beings are a class of autopoietic systems
able to conserve molecular information, a feature denoted by the term
semiopoiesis. By defining the molecular information of their products,
semiopoietic systems control their interaction with the medium and, by being able
to convey molecular information beneficial to the maintenance of the organization
to their offspring, semiopoietic systems can evolve by natural selection.
Information can be described as a specific state or order assumed among a set of
other possible states or orders. Thus, molecular information is the specific
order by which the molecular components are ordered, such as the sequence of
nucleotides in nucleic acids or of amino acids in proteins. However, molecular
information is not limited to copolymers. The atoms in small organic compounds
may also present diverse orders, giving rise to isomers. Different isomers can
present very distinct chemical and physical properties such that the biophysical
chemical properties of an organic compound are determined by its composition and
molecular information i.e. the specific positions in which their atoms are
posited. This molecular information can be conserved during reactions catalysed
by selective organocatalysts. In this way, organocatalysts appear as plausible
candidates to primitive hosts for the genetic information, before the emergence
of systems based in biopolymers. The bases of a putative organocatalysts-based
evolution are discussed. Finally, I argue that organocatalytic micelles can be
designed to produce programmable materials, artificial photosynthesis, self
building materials and artificial life with relevant industrial impact.
PMID- 28698019
TI - Corrigendum to "Effects of stereoscopic artificial floating wetlands on nekton
abundance and biomass in the Yangtze Estuary" [Chemosphere 183 (2017) 510-518].
PMID- 28698020
TI - First outbreak of colonization by linezolid- and glycopeptide-resistant
Enterococcus faecium harbouring the cfr gene in a UK nephrology unit.
AB - AIM: To describe an outbreak of colonization by linezolid- and glycopeptide
resistant Enterococcus faecium harbouring the cfr gene in a UK nephrology unit.
METHODS: Isolates of linezolid-resistant E. faecium were typed by pulsed-field
gel electrophoresis (PFGE), and examined by polymerase chain reaction (PCR) and
sequencing for the transmissible cfr gene that confers resistance to linezolid.
Enhanced environmental cleaning, initial and weekly screening of all patients,
and monitoring of adherence to standard infection control precautions were
implemented. FINDINGS: Five patients with pre-existing renal disease were found
to have rectal colonization with linezolid-resistant E. faecium over a two-week
period. The index case was a 57-year-old male from India who had travelled to the
UK. One patient also had a linezolid-resistant E. faecium of a different PFGE
profile isolated from a heel wound. All isolates were confirmed to harbour the
cfr gene by PCR and Sanger sequencing, and all were resistant to glycopeptides
(VanA phenotype). CONCLUSIONS: This article describes the first UK outbreak with
a single strain of linezolid- and glycopeptide-resistant E. faecium harbouring
the cfr gene, affecting five patients in a nephrology unit. Following the
implementation of aggressive infection control measures, no further cases were
detected beyond a two-week period.
PMID- 28698021
TI - Impact of an antimicrobial stewardship programme to optimize antimicrobial use
for outpatients at an emergency department.
AB - BACKGROUND: Antimicrobial stewardship programmes (ASPs) have been effective in
optimizing antibiotic use for inpatients. However, an emergency department's fast
paced clinical setting can be challenging for a successful ASP. AIM: In April
2015, an ASP was implemented in our emergency department and we aimed to
determine its impact on antimicrobial use for outpatients. METHODS: This was a
single-centre study comparing the quality of antibiotic prescriptions between a
one-year period before ASP implementation (November 2012 to October 2013) and a
one-year period after its implementation (June 2015 to May 2016). For each
period, antimicrobial prescriptions for all adult outpatients (hospitalized for
<24h) were evaluated by an infectious disease specialist and an emergency
department physician to assess compliance with local prescribing guidelines.
Inappropriate prescriptions were then classified. FINDINGS: Before and after ASP,
34,671 and 35,925 consultations were registered at our emergency department, of
which 25,470 and 26,208 were outpatients. Antimicrobials were prescribed in 769
(3.0%) and 580 (2.2%) consultations, respectively (P < 0.0001). There were 484
(62.9%) and 271 (46.7%) (P < 0.0001) instances of non-compliance with guidelines
before and after ASP implementation. Non-compliance included unnecessary
antimicrobial prescriptions, 197 (25.6%) vs 101 (17.4%) (P<0.0005); inappropriate
spectrum, 108 (14.0%) vs 54 (9.3%) (P=0.008); excessive treatment duration, 87
(11.3%) vs 53 (9.1%) (P>0.05); and inappropriate choices, 11 (1.4%) vs 15 (2.6%)
(P>0.05). CONCLUSION: The implementation of an ASP markedly decreased the number
of unnecessary antimicrobial prescriptions, but had little impact on most other
aspects of inappropriate prescribing.
PMID- 28698022
TI - Sexual orientation and neurocognitive ability: A meta-analysis in men and women.
AB - The cross-sex-shift hypothesis predicts that homosexual men and women will be
similar in certain neurobehavioral traits to their opposite-sex counterparts.
Accordingly, it predicts that homosexual men should perform in the direction of
heterosexual women, and homosexual women in the direction of heterosexual men, on
neurocognitive tests that show normative sex differences. We conducted a meta
analysis on the relationship between sexual orientation and cognitive
performance, and tested the effects of potential moderating variables separately
by sex. A total of 106 samples and 254,231 participants were included. The meta
analysis revealed that homosexual men performed like heterosexual women in both
male-favouring (e.g., spatial cognition) and female-favouring (e.g., verbal
fluency) cognitive tests, while homosexual women performed like heterosexual men
only in male-favouring tests. The magnitude of the sexual orientation difference
varied across cognitive domains (larger for spatial abilities). It was also
larger in studies comparing exclusive heterosexuals with exclusive homosexuals
compared to studies comparing exclusive heterosexuals with non-exclusive
homosexuals for both sexes. The results may narrow down potential sites for
sexual orientation-related neural differences.
PMID- 28698023
TI - Inhibitory effects of serratene-type triterpenoids from Lycopodium complanatum on
cholinesterases and beta-secretase 1.
AB - Phytochemical investigation of Lycopodium complanatum whole plants led to the
isolation of two new serratene-type triterpenoids (1 and 2) along with eight
known triterpenoids (3-10). Their structures were established using 1D and 2D NMR
spectroscopic techniques and mass spectrometry. These compounds did not inhibit
acetylcholinesterases (AChE) and butyrylcholinesterase (BChE), but did inhibit
beta-secretase 1 (BACE1). Compounds 1 and 6 showed potent BACE1 inhibition with
IC50 values of 2.79 +/- 0.28 and 2.49 +/- 0.12 MUM, respectively. The kinetic
study of BACE1 inhibition revealed that compound 1 showed competitive inhibition,
whereas 6 showed mixed-type inhibition. Furthermore, molecular docking results
showed that the tested inhibitors 1 and 6 exhibited good binding affinities
toward BACE1, with binding energies of -8.8 and -10.3 kcal/mol, respectively.
PMID- 28698024
TI - The prevalence and characteristics of cow's milk protein allergy in infants and
young children with iron deficiency anemia.
AB - BACKGROUND: The clinical presentation of cow's milk protein allergy (CMPA) in
children varies. This retrospective study aimed to investigate the prevalence and
clinical manifestations of CMPA in young children who visited for evaluation of
iron deficiency anemia (IDA). METHODS: Patients aged <4 years who were diagnosed
as having IDA (serum ferritin <12 ng/mL) at the National Cheng Kung University
Hospital, Taiwan in the period 2005-2015 were reviewed. Their clinical
presentations, laboratory data, endoscopy findings, and prognosis were analyzed.
RESULTS: Seven of 51 IDA patients (13.7%) had CMPA. The pallor (100%), failure to
thrive (43%), and general edema (43%) were the common features. Six (86%) had
hypoalbuminemia and four (57%) had positive occult blood in the stool. Of the
five patients who underwent skin prick test, four (80%) had positive results.
Most of the colonoscopies revealed erosive and hemorrhagic colitis and lymphoid
hyperplasia, but none of the biopsies demonstrated eosinophilia in the lamina
propria. All of the patients recovered from their IDA within seven months of
cow's milk protein elimination and iron supplementation. CONCLUSION: CMPA should
be considered in young children with undetermined IDA. Cow's milk protein
elimination and iron supplementation help in the recovery.
PMID- 28698025
TI - Bifurcation of the respiratory response to lung inflation in anesthetized dogs.
AB - Numerous studies have demonstrated the effect of lung volume on prolongation of
duration of expiration (TE) with limited understanding of the TE shortening and
termination of expiration as observed in newborn. In 14 dogs, the effects of
varied onset of lung inflation during expiration on the TE were evaluated. When
lung inflation was applied in the first part of expiration (20-60% of TE) TE was
lengthened. However, in the second portion (60-80% of TE) of expiration, lung
inflation either terminated or prolonged TE; whereas in the last portion of
expiration (80-90% of TE), lung inflation tended to terminate expiration
prematurely. The effects were abolished after bilateral vagotomy. We postulate
that prolongation of TE relates to the Breuer-Hering inflation reflex, which
increases the time needed for a passive expiration; whereas the ability to
shorten TE could relate to Head's paradoxical reflex acting to initiate
inspiration or to activate inspiratory motor activity to brake expiratory flow as
occurs in the newborn.
PMID- 28698026
TI - Corrigendum to "Thiol-ene Michael-type formation of gelatin/poly(ethylene glycol)
biomatrices for three-dimensional mesenchymal stromal/stem cell administration to
cutaneous wounds" [Acta Biomater. 9(11) (2013) 8802-8814].
PMID- 28698027
TI - Access to yellow fever travel vaccination centres in England, Wales, and Northern
Ireland: A geographical study.
AB - BACKGROUND: More than 700,000 trips were made by residents in England, Wales, and
Northern Ireland (EWNI) in 2015 to tropical countries endemic for yellow fever, a
potentially deadly, yet vaccine-preventable disease transmitted by mosquitoes.
The aim of this study was to map the geographical accessibility of yellow fever
vaccination centres (YFVC) in EWNI. METHODS: The location of 3208 YFVC were
geocoded and the average geodetic distance to nearest YFVC was calculated for
each population unit. Data on trips abroad and centres were obtained regionally
for EWNI and nationally for the World Top20 countries in terms of travel.
RESULTS: The mean distance to nearest YFVC was 2.4 km and only 1% of the
population had to travel more than 16.1 km to their nearest centre. The number of
vaccines administered regionally in EWNI was found correlated with the number of
trips to yellow fever countries. The number of centres per 100,000 trips was 6.1
in EWNI, which was below United States (12.1) and above the rest of Top20
countries. CONCLUSIONS: The service availability was in line with demand
regionally. With the exception of remote, rural areas, yellow fever vaccination
services were widely available with only short distances to cover for the
travelling public.
PMID- 28698028
TI - Animal bite and non-vector-borne transmission of Zika virus.
PMID- 28698029
TI - Critical role of EphA4 in early brain injury after subarachnoid hemorrhage in
rat.
AB - Early brain injury (EBI) is reported as a primary cause of mortality in
subarachnoid hemorrhage (SAH) patients. Eph receptor A4 (EphA4) has been
associated with blood-brain barrier integrity and pro-apoptosis. We aimed to
investigate a role of EphA4 in EBI after SAH. One hundred and seventy-nine male
adult Sprague-Dawley rats were randomly divided into sham versus endovascular
perforation model of SAH groups. SAH grade, neurological score, Evans blue dye
extravasation, brain water content, mortality, Fluoro-Jade staining,
immunofluorescence staining, and western blot experiments were performed after
SAH. Small interfering RNA (siRNA) for EphA4, recombinant Ephexin-1 (rEphx-1),
and Fasudil, a potent ROCK2 inhibitor, were used for intervention to study a role
of EphA4 on EBI after SAH. The expression of EphA4, Ephexin-1, RhoA, and ROCK2
significantly increased after SAH. Knockdown of EphA4 using EphA4 siRNA injection
intracerebroventricularly (i.c.v) reduced Evans blue extravasation, decreased
brain water content, and alleviated neurobehavioral dysfunction after SAH.
Additionally, the expression of Ephexin-1, RhoA, ROCK2 and cleaved caspase-3 were
decreased. Tight junction proteins increased, and apoptotic neuron death
decreased. The effects of EphA4 siRNA were abolished by rEphx-1. In contrast,
Fasudil abolished the effects of rEphx-1. These results suggest that EphA4, a
novel and promising target for treatment, exacerbates EBI through an Ephexin
1/ROCK2 pathway after SAH.
PMID- 28698030
TI - Myelination of axons emerging from neural progenitor grafts after spinal cord
injury.
AB - Neural progenitor cells (NPCs) grafted to sites of spinal cord injury (SCI)
extend numerous axons over long distances and form new synaptic connections with
host neurons. In the present study we examined the myelination of axons emerging
from NPC grafts. Rat embryonic day 14 (E14) multipotent NPCs constitutively
expressing GFP were grafted into adult C5 spinal cord hemisection lesions;
3months later we examined graft-derived axonal diameter and myelination using
transmission electron microscopy. 104 graft-derived axons were characterized.
Axon diameter ranged from 0.15 to 1.70MUm, and 24% of graft-derived axons were
myelinated by host oligodendrocytes caudal to the lesion. The average diameter of
myelinated axons (0.72+/-0.3MUm) was significantly larger than that of non
myelinated axons (0.61+/-0.2MUm, p<0.05). Notably, the G-ratio of myelinated
graft-derived axons (0.77+/-0.01) was virtually identical to that of the normal,
intact spinal cord described in published reports. These findings indicate that
axons emerging from early stage neural grafts into the injured spinal cord
recapitulate both the small/medium size range and myelin thickness of intact
spinal cord axons.
PMID- 28698031
TI - Comparable impediment of cognitive function in female and male rats subsequent to
daily administration of haloperidol after traumatic brain injury.
AB - Antipsychotic drugs, such as haloperidol (HAL), are prescribed in the clinic to
manage traumatic brain injury (TBI)-induced agitation. While preclinical studies
have consistently shown that once-daily administration of HAL hinders functional
recovery after TBI in male rats, its effects in females are unknown. Hence, the
objective of this study was to directly compare neurobehavioral and histological
outcomes in both sexes to determine whether the reported deleterious effects of
HAL extend to females. Anesthetized adult female and male rats received either a
controlled cortical impact (CCI) or sham injury and then were randomly assigned
to a dosing regimen of HAL (0.5mg/kg, i.p.) or vehicle (VEH; 1mL/kg, i.p.) that
was initiated 24h after injury and continued once daily for 19 consecutive days.
Motor function was tested using established beam-balance/walk protocols on post
operative days 1-5 and acquisition of spatial learning was assessed with a well
validated Morris water maze task on days 14-19. Cortical lesion volume was
quantified at 21days. No statistical differences were revealed between the HAL
and VEH-treated sham groups and thus they were pooled for each sex. HAL only
impaired motor recovery in males (p<0.05), but significantly diminished spatial
learning in both sexes (p<0.05). Females, regardless of treatment, exhibited
smaller cortical lesions vs VEH-treated males (p<0.05). Taken together, the data
show that daily HAL does not prohibit motor recovery in females, but does
negatively impact cognition. These task-dependent differential effects of HAL in
female vs male rats may have clinical significance as they can direct therapy.
PMID- 28698033
TI - Online communication in a rehabilitation setting: Experiences of patients with
chronic conditions using a web portal in Denmark.
AB - OBJECTIVE: To gain insight into the experiences of patients with long-term
conditions enrolled in an online rehabilitation programme using a web portal.
METHODS: Danish outpatients were recruited from a rehabilitation department and
were granted access to a web portal which included an online rehabilitation
programme with key information, clinical advice, and self-management activities.
After two weeks, patients were invited to participate in focus groups. A topic
guide was used to explore this new online rehabilitation programme in relation to
participants' experiences. RESULTS: Fourteen participants, ranging from 42 to 72
years old, were allocated into three focus groups. Participants mainly reported
negative experiences by the following four themes: 'patients' experiences',
'technical aspects', 'areas for improvement', and 'digitalization added value'.
CONCLUSION: Participants mainly reported negative experiences and suggested
combining both face-to-face consultations with online care by user-friendly web
portals. This will ensure a positive contribution from digital communication
tools to rehabilitation. PRACTICE IMPLICATIONS: Patients' experiences should be
considered in the design of web portals in rehabilitation which could help
healthcare organizations when developing online rehabilitation programmes.
PMID- 28698034
TI - Exploring physicians' verbal and nonverbal responses to cues/concerns: Learning
from incongruent communication.
AB - OBJECTIVES: Explore physicians' verbal and nonverbal responses to cues/concerns
in consultations with older-patients. METHODS: Two teams independently coded a
sample of Norwegian consultations (n=24) on verbal and nonverbal dimensions of
communication using VR-CoDES and NDEPT instruments. Consultations exploring older
patients' verbal emotional expressions were labeled 'Acknowledging of patients'
emotional expressions', and 'Distancing from patients' emotional expressions.'
Based on type and extent of nonverbal expressiveness, consultations were labeled
'Affective' and 'Prescriptive.' Congruency of verbal and nonverbal communication
was assessed and categorized into four types. Incongruent consultations were
qualitatively analyzed. RESULTS: Types 1 and 2 consultations were described as
'Congruent,' i.e. both verbal and nonverbal behaviors facilitate or inhibit
emotional expressions. Types 3 and 4 were considered 'Incongruent,' i.e. verbal
inhibits, but nonverbal facilitates emotional expressions or vice versa. Type 3
incongruent encounters occurred most often when it was challenging to meet
patients' needs. CONCLUSIONS: Frequently physicians' display incongruent behavior
in challenging situations. Older patients' may perceive this as either
alleviating or increasing distress, depending on their needs. PRACTICE
IMPLICATIONS: Type 3 consultations may shed light on reasons for physicians'
incongruent behavior; therefore, independent measurement and analyses of verbal
and nonverbal communication are recommended. Older-patients' perceptions of
incongruent communication should be further explored.
PMID- 28698032
TI - Beyond infection - Maternal immune activation by environmental factors,
microglial development, and relevance for autism spectrum disorders.
AB - Immune molecules such as cytokines and chemokines and the cells that produce them
within the brain, notably microglia, are critical for normal brain development.
This recognition has in recent years led to the working hypothesis that
inflammatory events during pregnancy, e.g. in response to infection, may disrupt
the normal expression of immune molecules during critical stages of neural
development and thereby contribute to the risk for neurodevelopmental disorders
such as autism spectrum disorder (ASD). This hypothesis has in large part been
shepherded by the work of Dr. Paul Patterson and colleagues, which has elegantly
demonstrated that a single viral infection or injection of a viral mimetic to
pregnant mice significantly and persistently impacts offspring immune and nervous
system function, changes that underlie ASD-like behavioral dysfunction including
social and communication deficits. Subsequent studies by many labs - in humans
and in non-human animal models - have supported the hypothesis that ongoing
disrupted immune molecule expression and/or neuroinflammation contributes to at
least a significant subset of ASD. The heterogeneous clinical and biological
phenotypes observed in ASD strongly suggest that in genetically susceptible
individuals, environmental risk factors combine or synergize to create a tipping
or threshold point for dysfunction. Importantly, animal studies showing a link
between maternal immune activation (MIA) and ASD-like outcomes in offspring
involve different species and diverse environmental factors associated with ASD
in humans, beyond infection, including toxin exposures, maternal stress, and
maternal obesity, all of which impact inflammatory or immune pathways. The goal
of this review is to highlight the broader implications of Dr. Patterson's work
for the field of autism, with a focus on the impact that MIA by diverse
environmental factors has on fetal brain development, immune system development,
and the pathophysiology of ASD.
PMID- 28698035
TI - Concordance of results of blood and tissue cultures from patients with pyogenic
spondylitis: a retrospective cohort study.
AB - OBJECTIVES: To investigate the concordance of results of blood and tissue
cultures in patients with pyogenic spondylitis. METHODS: We searched for patients
with pyogenic spondylitis in whom microorganisms were isolated from both blood
and tissue cultures by retrospective review of medical records in three tertiary
university-affiliated hospitals between January 2005 and December 2015. The
species and antimicrobial susceptibility patterns of isolates from blood and
tissue cultures were compared. RESULTS: Among 141 patients with pyogenic
spondylitis in whom microorganisms were isolated from both blood and tissue
cultures, the species of blood and tissue isolates were identical in 135 patients
(95.7%, 135/141). Excluding the four anaerobic isolates, we investigated
antimicrobial susceptibility patterns of 131 isolates of the same species from
blood and tissue cultures. Antibiotic susceptibility patterns were identical in
128 patients (97.7%, 128/131). The most common isolates were Staphylococcus
aureus (86 patients; 85 concordant and one discordant), followed by streptococcus
(24 patients; 22 concordant and two discordant), and Escherichia coli (eight
patients; all concordant). CONCLUSIONS: We suggest that a positive blood culture
from patients with pyogenic spondylitis could preclude the need for additional
tissue cultures, especially when S. aureus and streptococcus grew in blood
cultures.
PMID- 28698036
TI - Surgical site infection with extended-spectrum beta-lactamase-producing
Enterobacteriaceae after cardiac surgery: incidence and risk factors.
AB - OBJECTIVE: To determine the incidence, microbiology and risk factors for sternal
wound infection (SWI) with extended-spectrum beta-lactamase-producing
Enterobacteriaceae (ESBL-PE) following cardiac surgery. METHODS: We performed a
retrospective analysis between January 2006 and December 2015 of prospective
surveillance of a cohort of patients with cardiac surgery at a single centre
(Paris, France). SWI was defined as the need for reoperation due to sternal
infection. All patients with an initial surgery under extracorporeal circulation
and diagnosed with an SWI caused by Enterobacteriaceae isolates were included. We
compared patients infected with at least one ESBL-PE with those with SWI due to
other Enterobacteriaceae by logistic regression analysis. RESULTS: Of the 11 167
patients who underwent cardiac surgery, 412 (3.7%) developed SWI, among which
Enterobacteriaceae were isolated in 150 patients (36.5%), including 29 ESBL-PE.
The main Enterobacteriaceae (n = 171) were Escherichia coli in 49 patients (29%)
and Enterobacter cloacae in 26 (15%). Risk factors for SWI with ESBL-PE in the
multivariate logistic regression were previous intensive care unit admission
during the preceding 6 months (adjusted odds ratio (aOR) 12.2; 95% CI 3.3-44.8),
postoperative intensive care unit stay before surgery for SWI longer than 5 days
(aOR 4.6; 95% CI 1.7-11.9) and being born outside France (aOR 3.2; 95% CI 1.2
8.3). CONCLUSIONS: Our results suggest that SWI due to ESBL-PE was associated
with preoperative and postoperative unstable state, requiring an intensive care
unit stay longer than the usual 24 or 48 postoperative hours, whereas being born
outside France may indicate ESBL-PE carriage before hospital admission.
PMID- 28698037
TI - Cefazolin versus anti-staphylococcal penicillins for treatment of methicillin
susceptible Staphylococcus aureus bacteraemia: a narrative review.
AB - BACKGROUND: Anti-staphylococcal penicillins (ASPs) are recommended as first-line
agents in methicillin-susceptible Staphylococcus aureus (MSSA) bacteraemia.
Concerns about their safety profile have contributed to the increased use of
cefazolin. The comparative clinical effectiveness and safety profile of cefazolin
versus ASPs for such infections remain unclear. Furthermore, uncertainty persists
concerning the use of cefazolin due to controversies over its efficacy in deep
MSSA infections and its possible negative ecological impact. AIMS: The aim of
this narrative review was to gather and balance available data on the efficacy
and safety of cefazolin versus ASPs in the treatment of MSSA bacteraemia and to
discuss the potential negative ecological impact of cefazolin. SOURCES: PubMed
and EMBASE electronic databases were searched up to May 2017 to retrieve
available studies on the topic. CONTENTS: Although described in vitro and in
experimental studies, the clinical relevance of the inoculum effect during
cefazolin treatment of deep MSSA infections remains unclear. It appears that
there is no significant difference in rate of relapse or mortality between ASPs
and cefazolin for the treatment of MSSA bacteraemia but these results should be
cautiously interpreted because of the several limitations of the available
studies. Compared with cefazolin, there is more frequent discontinuation for
adverse effects with ASP use, especially because of cutaneous and renal events.
No study has evidenced any change in the gut microbiota after the use of
cefazolin. IMPLICATIONS: Based on currently available studies, there are no data
that enable a choice to be made of one antibiotic over the other except in
patients with allergy or renal impairment. This review points out the need for
future prospective studies and randomized controlled trials to better address
these questions.
PMID- 28698038
TI - Multidrug-resistant/extensively drug-resistant tuberculosis in Greece:
predominance of Mycobacterium tuberculosis genotypes endemic in the Former Soviet
Union countries.
PMID- 28698039
TI - Viral dynamics of persistent hepatitis C virus infection in high-sensitive
reporter cells resemble patient's viremia.
AB - BACKGROUND: Hepatitis C virus (HCV) infection has a high persistence rate in
patients. Although immune cells play a central role in determining the outcomes
of HCV infection, the liver is crucial in controlling HCV activity from acute to
chronic stages. This investigation grew HCV from a long-term cell culture, and
provided an experimental model for studies on HCV persistence in hepatocytes.
METHODS: Huh7.5 cells implanted with the NS3/4 protease-based secreted alkaline
phosphatase (SEAP) reporter were infected with JFH-1 HCV (moiety of infection =
0.01) and incubated for over 130 days. RESULTS: The viral activity was obtained
by sampling supernatant continuously for SEAP activity measurement. Combined with
extracellular and intracellular HCV-RNAs and viral infectivity assays, the
experimental results exhibited in vitro viral dynamics resembling the patients'
viremia pattern from acute to chronic infections. The HCV in acute infection
comprised exponential accumulation (week 1), plateau (week 2), declining
production (weeks 3-4) and silencing (weeks 5-14) phases, and were then
reactivated at the onset of chronic infection (after week 15). The HCV-infected
cells grew more slowly than the mock controls, and exhibited a prominent decrease
of cell growth rate and increase of early apoptosis in the declining-to-silencing
phase transition, suggesting that fitness selection might occur as the infected
cells moved across the boundary of active to occult viral activity. CONCLUSION:
Cultivated HCV in the highly sensitive NS3/4-based SEAP reporter cells could
establish persistence, which might mimic the viral dynamics from acute to chronic
infections in hepatitis C patients.
PMID- 28698040
TI - Role of class II P fimbriae and cytokine response in the pathogenesis of
Escherichia coli kidney infection in diabetic mice.
AB - BACKGROUND: The role of class II P fimbriae (P fimbriae II) in diabetic kidney
infections is uncertain, although some genetic and epidemiological studies
suggest a lower prevalence of P fimbriae II genes in Escherichia coli strains
isolated from diabetic patients with complicated kidney infections. METHODS: We
inoculated a P fimbriae II deficient E. coli (DH5alphaT) or an isogenic P
fimbriae II expressing transformant (DH5alphaTP) into the bladders of diabetic
and non-diabetic BALB/C mice, and sacrificed them after 3 days. The incidence of
bladder or kidney infection (>=103 CFU of E. coli per bladder or kidney),
bacteremia (>=102 CFU of E. coli on blood culture plate), kidney pathological
score, immunoreactive Histo-score (H-score), and corrected H-score (H-score
adjusted for Log10 CFU of bacteria in the kidney) were compared among groups.
RESULTS: Diabetic mice were more susceptible to bladder infection than non
diabetic mice with both transformants. The geometric mean of bacteria counts in
kidneys was significantly increased only when the diabetic mice were infected
with DH5alphaTP. Among the 4 groups of mice, diabetic mice infected with
DH5alphaTP had the highest incidence of kidney infection and bacteremia, and the
highest renal pathology scores. The IL-8 H-score and the corrected IL-6 and IL-8
H-score were significantly lower in diabetic than non-diabetic mice. CONCLUSION:
We concluded that P fimbriae II contribute to the pathogenesis and severity of E.
coli kidney infections in diabetic mice. An impaired cytokine response may also
contribute to the increased incidence and severity of kidney infections in
diabetic hosts.
PMID- 28698041
TI - Streptococcus sanguis bacteremia complicating endocarditis associated with
colonic adenocarcinoma.
PMID- 28698042
TI - Propensity-matched analysis of the impact of extended-spectrum beta-lactamase
production on adults with community-onset Escherichia coli, Klebsiella species,
and Proteus mirabilis bacteremia.
AB - BACKGROUND: The presence of extended-spectrum beta-lactamase (ESBL) in
Escherichia coli, Klebsiella species, and Proteus mirabilis (EKP) is of great
microbiological and clinical importance. The study dealing with the direct impact
of ESBL producers on the outcome of patients with community-onset bacteremia is
lacking. METHODS: Adults with community-onset EKP bacteremia were recruited
retrospectively during a 6-year period. ESBL producers were determined according
to ESBL phenotype. ESBL patients were compared on a 1:2 basis with non-ESBL
patients by using propensity-score matching (PSM) calculated based on independent
predictors of 28-day mortality. RESULTS: Of the 1141 eligible adult patients, 65
(5.7%) caused by ESBL producers. Significant differences between the two groups
were discovered in the proportions of patients with critical illness (a Pitt
bacteremia score >= 4) at bacteremia onset, inappropriate empirical antibiotic
therapy, bacteremia because of urosepsis and pneumonia, and several
comorbidities. In a PSM analysis after controlling for six independent predictors
critical illness at bacteremia onset, underlying fatal comorbidities (McCabe
classification), inappropriate empirical antibiotic therapy, comorbidities with
liver cirrhosis, bacteremia because of urosepsis and pneumonia-a appropriate
matching between two groups (ESBL group, 60 patients; non-ESBL group, 120) were
observed in age, causative microorganism, bacteremia severity, major
comorbidities, comorbidity severity, and major bacteremia source. Consequently, a
strong relationship between ESBL producers and poor prognosis was highlighted.
CONCLUSIONS: The adverse influence of ESBL producers on clinical outcomes was
presented with respect to adults with community-onset EKP bacteremia.
Establishing a predictive scoring algorithm for identifying patients at risk of
ESBL-producer infections is crucial.
PMID- 28698043
TI - Pulmonary empyema caused by co-infections of Mycoplasma pneumoniae and
Fusobacterium necrophorum: A rare case of lemierre syndrome.
PMID- 28698044
TI - Resistance to first- and second-line antituberculosis drugs in Southern Taiwan:
Implications for empirical treatment.
AB - BACKGROUND: Multidrug-resistant and extensively drug-resistant tuberculosis
infections cause public health concerns worldwide. Local epidemiologic data about
the drug resistance of Mycobacterium tuberculosis isolate (Mtb) is critical to
guide appropriate empirical therapy to cure patients and restrain the spread of
tuberculosis. METHODS: Antituberculosis susceptibility testing was performed for
287 Mtbs, including 63 MDR-Mtbs collected in southern Taiwan from 2011 to 2015.
Tuberculosis patients were classified into newly diagnosed cases and previously
treated cases based on patients' medical history. RESULTS: Almost no resistance
was found to the tested second-line antituberculosis drugs in non-MDR-Mtbs.
Higher resistance rates to ethambutol, ofloxacin, and streptomycin were observed
in MDR-Mtbs compared to non-MDR-Mtbs. Among 63 MDR-Mtbs, 61.9% of patients were
newly diagnosed and 38.1% were previously treated cases. For MDR-Mtb, the drug
resistance rates in previously treated cases were significantly higher for
ethambutol, pyrazinamide, ofloxacin, moxifloxacin, streptomycin, and p
aminosalicylic acid. When MDR-Mtbs are identified in previously treated cases,
empirical administration of ethambutol, pyrazinamide, ofloxacin, or moxifloxacin
may not provide effective treatment. The resistance rates to these drugs were all
more than 50%. Furthermore, 25% of MDR-Mtbs from previously treated patients were
resistant to p-aminosalicylic acid. CONCLUSION: We observed almost no resistance
to the tested second-line antituberculosis drugs among non-MDR-Mtbs. Anti
tuberculosis regimen with pyrazinamide, ethambutol, fluoroquinolone, kanamycin,
cycloserine and p-aminosalicylic acid can be empirically used for newly diagnosed
MDR-TB cases. For previously treated MDR-TB patients, empirical ethambutol,
pyrazinamide, ofloxacin, or moxifloxacin may not provide effective treatment
because the resistance rates to these drugs were all >50%.
PMID- 28698045
TI - Active and passive responses to catnip (Nepeta cataria) are affected by age, sex
and early gonadectomy in male and female cats.
AB - Catnip (Nepeta cataria) is a popular plant among cat owners because in about 60%
of felids elicits active behaviors such as rolling over, grooming, motor activity
and vocalizations. Herein, we assessed the display of active but also passive
responses, such as time in sphinx-like position, and consequently hypothesized
that 100% of cats respond to catnip. Accordingly, sixty domestic cats of
different age (infant, juvenile, adults), sex (males, females) and gonadal status
(early gonadectomized, gonadally intact) were placed in a cylindrical chamber
(1.20*1.40m) during 5min and then exposed to 500mg of dehydrated catnip for
another 5min. Behaviors were videorecorded and scored. Results indicated that
about 20% of the cats (adults and juvenile only) displayed active behaviors (i.e.
rolling over), whereas 80% displayed passive responses at any age (sphinx-like
position, decreased frequency in vocalizations, and decreased motor activity).
These results suggest that all cats respond to catnip but they express it
actively, passively or with a combination of both types of responses, which
mainly depends on age and sex, and early gonadectomy to a much less extent. We
discuss the possible implications of brain maturation on this dichotomy and
speculate on the role of opioidergic system on the catnip responses.
PMID- 28698046
TI - Simian varicella virus causes robust transcriptional changes in T cells that
support viral replication.
AB - Varicella zoster virus (VZV) causes varicella (chickenpox) during acute
infection. Several studies have shown that T cells are early and preferential
targets of VZV infection that play a critical role in disseminating VZV in to the
skin and ganglia. However, the transcriptional changes that occur in VZV-infected
T cells remain unclear due to limited access to clinical samples and robust
translational animal models. In this study, we used a nonhuman primate model of
VZV infection where rhesus macaques are infected with the closely related Simian
Varicella Virus (SVV) to provide novel insights into VZV-T cell interactions. RNA
sequencing of bronchial alveolar lavage-resident T cells isolated from infected
rhesus macaques show that SVV infection alters expression of genes important for
regulation of gene expression, cell cycle progression, metabolism, and antiviral
immunity. These data provide insight into cellular processes that may support
viral replication, facilitate SVV dissemination, and evade host defense.
PMID- 28698047
TI - Identification of a novel linear B-cell epitope in the p27 of Avian leukosis
virus.
AB - Avian leukosis virus (ALV) is an avian oncogenic retrovirus that can induce virus
associated neoplasia and causes great economic loss in poultry industry. It is
known that the capsid antigen p27 is the group-specific antigen that is highly
conserved among all ALV subgroups, and is the most abundant immunogenic viral
protein. In the present study, five overlapping fragments (GST- p27-F1/2, GST-
p27-F2-1/2/3) of ALV-p27 were subjected to Western blotting analysis using a
monoclonal antibody (5D3) against ALV-p27 to identify the epitope. The result
showed that the epitope recognized by 5D3 is located within 173-240 amino acid of
the ALV-p27 protein. For precise mapping of this epitope, a set of overlapping
peptides were synthesized. Indirect enzyme linked immunosorbent assay (ELISA)
revealed that 193CFRQKSQPDI202 motif was the minimal fragment recognized by 5D3,
so this motif represented a linear B-cell epitope of ALV-p27. Homology analysis
indicated that 5D3 defined epitope is highly conserved among ALV strains. The
identified epitope might be useful in clinical applications and as a tool for
further study of the structure and function of ALV-p27.
PMID- 28698048
TI - Identification and functional evaluation of two STAT3 variants in grass carp:
Implication for the existence of specific alternative splicing of STAT3 gene in
teleost.
AB - A STAT family member, STAT3, becomes activated as a DNA binding protein in
response to cytokines and growth factors. In teleost, STAT3 cDNA has been cloned
and identified in a few species, but only a single STAT3 transcript is revealed
in these studies. In the present study, two variants of STAT3 gene generated by
alternative splicing were isolated from grass carp and nominated as STAT3alpha1
and STAT3alpha2 based on the homology with their mammalian orthologs. In
particular, the homologs of STAT3alpha1/2 were also found in various fish
species, including zebrafish, takifugu, tilapia, medaka and goldfish.
Intriguingly, sequence alignment and genomic structure analysis revealed that
fish STAT3alpha1/2 are generated through similar alternative splicing events,
implying the potential physiological significance of generating STAT3 variants in
fish. Grass carp STAT3alpha1/2 (gcSTAT3alpha1/2) were ubiquitously expressed
although the transcript levels of STAT3alpha2 were markedly higher than
STAT3alpha1 in all examined tissues. In vivo and in vitro studies showed that the
expression patterns of these two variants were similar under the stimulation of
immune stimuli. To reveal the role of gcSTAT3alpha1/2 in fish immunity, their
phosphorylation and involvement in IL-17A/F1 mRNA expression were demonstrated in
grass carp peripheral blood lymphocytes upon LPS or PHA challenge, providing
evidence for the functional conservation of STAT3 signaling in fish. These
findings also raise a question of whether both gcSTAT3alpha1/2 participate in
transcriptional regulation in fish. Actually, our results showed that both of
them had the ability to translocate into the nucleus upon activation, and to
amplify IL-10 signaling, indicating the existence of STAT3 isoforms with
functional redundancy in teleost.
PMID- 28698049
TI - Tensins: Bridging AMP-Activated Protein Kinase with Integrin Activation.
AB - Integrin activation is essential for cell adhesion and for connecting the
extracellular matrix to the actin cytoskeleton. Thus, inappropriate integrin
activation has been linked to several diseases, including cancer. Recent insights
demonstrate that the main fibrillar adhesion component tensin maintains beta1
integrin active in these mature adhesions. Depletion or silencing of AMP
activated protein kinase (AMPK), the energy sensor involved in maintaining the
energy balance of the cell, enhances integrin activity by increasing the
expression of tensin and thereby promoting cell adhesion, matrix formation, and
mechanotransduction. Here, we discuss the role of tensin and AMPK in the
regulation of integrin activity and integrin-dependent processes and their
implication in diseases such as cancer and tissue fibrosis.
PMID- 28698050
TI - [Brugada pattern unmasked by propafenone in an 84-years-old man].
PMID- 28698051
TI - Effects of pituitary adenylate cyclase activating polypeptide on small intestinal
INT 407 cells.
AB - Pituitary adenylate cyclase activating polypeptide (PACAP) is an endogenous
neuropeptide having a widespread distribution both in the nervous system and
peripheral organs including the gastrointestinal tract. It has been shown to
exert actions on intestinal functions, mainly affecting glandular secretion and
motility. PACAP has several different effects on cell survival depending on the
cell type and the applied stimulus. Its influences on small intestinal epithelial
cells are not yet elucidated, therefore the aim of the present study was to
investigate the effects of PACAP on intestinal epithelial cells having high
turnover (INT 407) against different harmful stimuli, such as oxidative stress,
in vitro hypoxia and gamma radiation. We tested the effect of PACAP on
proliferation and cell survival using MTT assay. Moreover, various cancer-related
factors were evaluated by oncology array. PACAP did not influence the
proliferation rate of INT 407 cells. Its cell survival-enhancing effect could be
detected against oxidative stress, but not against in vitro hypoxia or gamma
irradiation. Clonogenic survival assay was performed to analyze the effect of
PACAP on clonogenic potential of cells exposed to gamma radiation. Surprisingly,
PACAP enhanced the clone-forming ability decrease induced by irradiation. Western
blot analysis of ERK1/2 phosphorylation was performed in order to obtain further
information on the molecular background. Our data showed phospho-ERK1/2
suppression of PACAP in irradiated cells. Furthermore, the role of endogenous
PACAP against oxidative stress was also investigated performing ADCYAP1 small
interfering RNA transfection. We found significant difference in the cell
vulnerability between cells undergoing silencing and cells without transfection
suggesting the protective role of the endogenously present PACAP against
oxidative stress in INT 407 cells. In summary, PACAP seems to be able to exert
contradictory effects in INT 407 cells depending on the applied stressor,
suggesting its regulatory role in the cellular household.
PMID- 28698052
TI - Attempt to simultaneously generate three chiral centers in 4-hydroxyisoleucine
with microbial carbonyl reductases.
AB - A panel of microorganisms was screened for selective reduction ability towards a
racemic mixture of prochiral 2-amino-3-methyl-4-ketopentanoate (rac-AMKP).
Several of the microorganisms tested produced greater than 0.5mM 4
hydroxyisoleucine (HIL) from rac-AMKP, and the stereoselectivity of HIL formation
was found to depend on the taxonomic category to which the microorganism
belonged. The enzymes responsible for the AMKP-reducing activity, ApAR and FsAR,
were identified from two of these microorganisms, Aureobasidium pullulans NBRC
4466 and Fusarium solani TG-2, respectively. Three AMKP reducing enzymes, ApAR,
FsAR, and the previously reported BtHILDH, were reacted with rac-AMKP, and each
enzyme selectively produced a specific composition of HIL stereoisomers. The
enzymes appeared to have different characteristics in recognition of the
stereostructure of the substrate AMKP and in control of the 4-hydroxyl group
configuration in the HIL product.
PMID- 28698053
TI - Stable C-N axial chirality in 1-aryluracil scaffold and differences in in vitro
metabolic clearance between atropisomers of PDE4 inhibitor.
AB - We report herein the stable C-N axial chirality in a 1-phenyl-6-aminouracil
scaffold owing to the presence of various functional groups at the ortho-position
of the N(1)-phenyl group. Racemic 1-phenyl-6-aminouracils were first separated by
chiral HPLC or converting them to the corresponding diastereomers using a chiral
resolving agent. We then determined the rotational barrier of each atropisomer by
a thermal racemization method and found that these compounds have rotational
barriers similar to other C-N axially chiral biaryls. In addition, there was a
good correlation between the rotational barriers and van der Waals radii of an
ortho-substituent of the N(1)-phenyl group. To explore the possibility of the
chiral 1-phenyl-6-aminouracil scaffold as a drug lead, we synthesized both
atropisomers as phosphodiesterase-4 inhibitors 10. The atropisomers showed
significantly different metabolic stabilities while their PDE4 inhibitory
activities were somewhat similar. This finding demonstrates the potential utility
of stable C-N bond atropisomers in the development of chiral drugs.
PMID- 28698054
TI - Bistacrines as potential antitrypanosomal agents.
AB - Human African Trypanosomiasis (HAT) is caused by two subspecies of the genus
Trypanosoma, namely Trypanosoma brucei rhodesiense and Trypanosoma brucei
gambiense. The disease is fatal if left untreated and therapy is limited due to
only five non-adequate drugs currently available. In preliminary studies, dimeric
tacrine derivatives were found to inhibit parasite growth with IC50-values in the
nanomolar concentration range. This prompted the synthesis of a small, but smart
library of monomeric and dimeric tacrine-type compounds and their evaluation of
antiprotozoal activity. Rhodesain, a lysosomal cathepsin-L like cysteine protease
of T. brucei rhodesiense is essential for parasite survival and likely target of
the tacrine derivatives. In addition, the inhibition of trypanothione reductase
by bistacrines was found. This flavoprotein oxidoreductase is the main defense
against oxidative stress in the thiol redox system unique for protozoa.
PMID- 28698055
TI - Small molecule metalloprotease inhibitor with in vitro, ex vivo and in vivo
efficacy against botulinum neurotoxin serotype A.
AB - Botulinum neurotoxins (BoNTs) are the most toxic substances known to mankind and
are the causative agents of the neuroparalytic disease botulism. Their ease of
production and extreme toxicity have caused these neurotoxins to be classified as
Tier 1 bioterrorist threat agents and have led to a sustained effort to develop
countermeasures to treat intoxication in case of a bioterrorist attack. While
timely administration of an approved antitoxin is effective in reducing the
severity of botulism, reversing intoxication requires different strategies. In
the present study, we evaluated ABS 252 and other mercaptoacetamide small
molecule active-site inhibitors of BoNT/A light chain using an integrated multi
assay approach. ABS 252 showed inhibitory activity in enzymatic, cell-based and
muscle activity assays, and importantly, produced a marked delay in time-to-death
in mice. The results suggest that a multi-assay approach is an effective strategy
for discovery of potential BoNT therapeutic candidates.
PMID- 28698056
TI - Daboia (Vipera) palaestinae envenomation in horses: Clinical and hematological
signs, risk factors for mortality and construction of a novel severity scoring
system.
AB - Daboia palaestinae is the most common venomous snake in Israel and an important
cause of envenomations in humans and animals. Although specific antivenom is
produced from horses, little documentation exists regarding the characteristics
of envenomed horses. This survey was constructed to describe the clinical,
hematological and biochemical characteristics of D. palaestinae envenomation in
horses, to identify risk factors for fatality and to construct a prognostic
snakebite severity scale (SSS) to be used by veterinarians in the field. Data
regarding 123 equine snakebite cases were collected over four years. Clinical
signs most frequently described were local swelling (100%), tachycardia (67%),
increased respiratory effort (62%), bite marks (44%) and reduced appetite (50%).
Blood samples were collected at initial presentation from 23 of these horses.
Hematological and biochemical abnormalities described in the majority of the
sampled cases included leukocytosis (52%), neutrophilia (78%), increased creatine
phosphokinase (77%), hypoproteinemia (50%), decreased total carbon dioxide (54%),
and hyperphosphatemia (54%). The overall case fatality rate was 20.3% (25/123
horses). Risk factors associated with increased mortality (P < 0.05) were body
weight below 200 kg, hind limb envenomation, severity of local swelling, mental
status, respiratory effort, bleeding disorders, dehydration, basophilia,
monocytosis, bilirubinemia, hypocalcemia and hyperphosphatemia. These risk
factors were used to construct an SSS adapted for the assessment of envenomed
horses in the field, consisting of seven dichotomous parameters. A cutoff value
of 1.5 predicted mortality with 95% sensitivity and 68% specificity. In the
future, this tool could assist clinicians with case management and communication
with owners.
PMID- 28698058
TI - US guided wire localization of malignant melanoma subcutaneous metastases.
PMID- 28698057
TI - Membrane Trafficking in Plant Immunity.
AB - Plants employ sophisticated mechanisms to interact with pathogenic as well as
beneficial microbes. Of those, membrane trafficking is key in establishing a
rapid and precise response. Upon interaction with pathogenic microbes, surface
localized immune receptors undergo endocytosis for signal transduction and
activity regulation while cell wall components, antimicrobial compounds, and
defense proteins are delivered to pathogen invasion sites through polarized
secretion. To sustain mutualistic associations, host cells also reprogram the
membrane trafficking system to accommodate invasive structures of symbiotic
microbes. Here, we provide an analysis of recent advances in understanding the
roles of secretory and endocytic membrane trafficking pathways in plant immune
activation. We also discuss strategies deployed by adapted microbes to manipulate
these pathways to subvert or inhibit plant defense.
PMID- 28698059
TI - Is there an advantage in onset of action with mixing lignocaine and bupivacaine?
PMID- 28698060
TI - Assessment of left ventricular function and geometry in hypertensive patients:
Novel approaches in every day clinical practice.
PMID- 28698061
TI - The accuracy of the anatomical method for stature estimation in Black South
African females.
AB - The anatomical method is considered the most accurate stature estimation method,
but investigation has shown that it continuously underestimates stature. This
underestimation is believed to be related to the use of universal soft tissue
correction factors. Therefore, the aim of this study was to assess the accuracy
of the soft tissue correction factors in a living population of Black South
African females and to subsequently calculate a new soft tissue correction
factor, specific for stature estimation in this population group. Thirty Black
South African adult females voluntarily participated in this study and underwent
a full body Magnetic Resonance Imaging (MRI) scan. Living stature was measured
with a stadiometer and total skeletal height (TSH) was calculated from the MRI
measurements. Stature was estimated from the TSH of each participant using
Fully's (1956) [17], Raxter et al.'s (2006) [38] and Bidmos and Manger's (2012)
[5] methods. Results indicated strong, statistically significant positive
correlations between living and estimated statures, however, paired t-tests
revealed that living stature was significantly underestimated using Fully's and
Raxter et al.'s methods, while the method by Bidmos and Manger significantly
overestimated stature. A lack of statistically significant correlations between
soft tissue correction factors and the total skeletal height was found. Likewise,
an absence of statistically significant correlations between age and the
estimation error, with and without age adjustments were also observed. A new soft
tissue correction factor, specific for stature estimation in Black South African
females was calculated. The newly proposed regression equation presented improved
stature estimation accuracies for this population group.
PMID- 28698062
TI - The clandestine multiple graves in Malaysia: The first mass identification
operation of human skeletal remains.
AB - The first ever mass identification operation of skeletal remains conducted for
the clandestine graves in Malaysia consisted of 165 individuals unearthed from 28
human trafficking transit camps located in Wang Kelian, along the Thai-Malaysia
border. A DVI response was triggered in which expert teams comprising of
pathologists, anthropologists, odontologists, radiologists and DNA experts were
gathered at the identified operation centre. The Department of Forensic Medicine,
Hospital Sultanah Bahiyah, Alor Star, Kedah, located approximately 75km away from
Wang Kelian, was temporarily converted into a victim identification centre (VIC)
as it is the nearest available forensic facility to the mass grave site. The
mortuary operation was conducted over a period of 3 months from June to September
2015, and was divided into two phases; phase 1 involving the postmortem
examination of the remains of 116 suspected individuals and for phase 2 the
remains of 49 suspected individuals. The fact that the graves were of unknown
individuals afforded the mass identification operation a sufficient duration of 2
weeks as preparatory phase enabling procedurals and daily victim identification
workflow to be established, and the setting up of a temporary body storage for
the designated mortuary. The temporary body storage has proven to be a
significant factor in enabling the successful conclusion of the VIC operation to
the final phase of temporary controlled burials. Recognition from two
international observers, Mr. Andreas Patino Umana, from the International
Committee of Red Cross (ICRC) and Prof. Noel Woodford from Victoria Institute of
Forensic Medicine (VIFM) had proven the mortuary operation was in compliance to
the international quality and standards. The overall victim identification and
mortuary operation identified a number of significant challenges, in particular
the management of commingled human remains as well as the compilation of
postmortem data in the absence of antemortem data for future reconciliation. CF
Index in this DVI operation is 9%, indicating the primary identifications in this
operation were effective. Limitations and further improvements of the mass
identification operation will be discussed. This paper details the planning,
preparations and management of the mass identification operation on the exhumed
human remains which was also a forensic humanitarian service for the dead with
dignity and respect.
PMID- 28698063
TI - Population variation in skeletal sexual dimorphism.
AB - Research has documented considerable population variation in sexual dimorphism
related to human growth and development. This variation represents both genetic
and environmental factors which impact methodologies used to estimate sex from
human skeletal remains. This article provides an overview of known variation in
skeletal sexual dimorphism among populations through documented research on
samples from around the world. Variation in juvenile growth patterns of
populations and differences in adult skeletal size and characteristics are
discussed. This recognized variation should be considered by forensic
anthropologists when estimating sex from skeletal remains and appropriate
population-specific data should be utilized.
PMID- 28698064
TI - MicroRNA-1 inhibits ovarian cancer cell proliferation and migration through c-Met
pathway.
AB - In this study, we investigated the differential expression of microRNAs in an
ovarian cancer cell line HO-8910PM with increased migration and invasiveness
activities. miR-1 was found to be one of the microRNA species most significantly
downregulated in HO-8910PM compared with the control cell line HO-8910. We
demonstrated that ovarian cancer tissues expressed decreased levels of miR-1
compared to non-neoplastic tissues. In vitro experiments showed that
overexpression of miR-1 in HO-8910PM led to an inhibition of cell proliferation,
blocking of cell cycle progression by G1 phase arrest, and decreased migration
and invasiveness of HO-8910PM cells. Moreover, we confirmed that the expression
of c-Met, a potential target of miR-1, was significantly inhibited following
overexpression of miR-1 in HO-8910PM cells. Further analyses indicated that
expression of factors including p-Akt, p-ERK1/2, CDK4, and p-Rb in HO-8910PM
cells were affected by manipulation of c-Met expression. Infection of HO-8910PM
cells with lentivirus vector expressing miR-1 led to a significant inhibition of
tumor growth in the tumor subcutaneous nude mouse model. Taken together, these
results indicated that miR-1 is downregulated in ovarian cancer tissues, and may
play a tumor suppressive role by inhibiting c-Met expression and its effects on
the regulation of cell proliferation, migration and invasion.
PMID- 28698065
TI - The effect of poly (lactic-co-glycolic) acid composition on the mechanical
properties of electrospun fibrous mats.
AB - The aim of this study was to investigate the influence of polymer molecular
structure on the electrospinnability and mechanical properties of electrospun
fibrous mats (EFMs). Polymers with similar molecular weight but different
composition ratios (lactic acid (LA) and glycolic acid (GA)) were dissolved in
binary mixtures of N,N-dimethylformamide (DMF) and tetrahydrofuran (THF). The
intrinsic viscosity and rheological properties of polymer solutions were
investigated prior to electrospinning. The morphology and mechanical properties
of the resulting EFMs were characterized by scanning electron microscope (SEM)
and dynamic mechanical analysis (DMA). Sufficiently high inter-molecular
interactions were found to be a prerequisite to ensure the formation of fibers in
the electrospinning process, regardless the polymer composition. The higher the
amount of GA in the polymer composition, the more ordered and entangled molecules
were formed after electrospinning from the solution in THF-DMF, which resulted in
higher Young's modulus and tensile strength of the EFMs. In conclusion, this
study shows that the mechanical properties of EFMs, which depend on the polymer
molecule-solvent affinity, can be predicted by the inter-molecular interactions
in the starting polymer solutions and over the drying process of electrospinning.
PMID- 28698066
TI - Nasal nanovaccines.
AB - Nasal administration of vaccines is convenient for the potential stimulation of
mucosal and systemic immune protection. Moreover the easy accessibility of the
intranasal route renders it optimal for pandemic vaccination. Nanoparticles have
been identified as ideal delivery systems and adjuvants for vaccine application.
Heterogeneous protocols have been used for animal studies. This complicates the
understanding of the formulation influence on the immune response and the
comparison of the different nanoparticles approaches developed. Moreover
anatomical and immunological differences between rodents and humans provide an
additional hurdle in the rational development of nasal nanovaccines. This review
will give a comprehensive expertise of the state of the art in nasal nanovaccines
in animals and humans focusing on the nanomaterial used.
PMID- 28698067
TI - Glycyrrhetinic acid-modified TPGS polymeric micelles for hepatocellular carcinoma
targeted therapy.
AB - In this study, glycyrrhetinic acid (GA)-modified D-alpha-tocopheryl polyethylene
glycol 1000 succinate (TPGS) polymeric micelles (TGA PMs) were developed for the
delivery of etoposide (ETO) to hepatoma cells. GA was incorporated as a ligand
because of its high affinity to the hepatocytes, while TPGS functioned as a P-gp
inhibitor to reverse multidrug resistance. ETO-loaded TGA PMs (ETO-TGA PMs)
displayed a mean particle size of 133.6+/-1.2nm with a low poly-dispersity index
(0.224+/-0.013) and negative zeta potential (-16.30mV). The drug loading and
entrapment efficiency of ETO-TGA PMs were 10.4% and 79.8%, respectively. ETO-TGA
PMs also exhibited faster drug release behavior at pH 5.8 and relatively stable
drug release at pH 7.4. Confocal laser scanning microscope (CLSM) observations
and in vivo imaging studies revealed that TGA PMs displayed higher cellular
uptake and selective accumulation at the tumor site, indicating good tumor
targetability. Furthermore, ETO-TGA PMs displayed significant cytotoxicity
towards HepG2 cells and higher anti-tumor efficacy (75.96%), compared to the
control group. This could be due to TGA-mediated targeted drug delivery to the
hepatocytes as well as P-gp inhibition. These findings suggest that TGA PMs have
the potential to be used as a targeted drug delivery system for hepatic cancer
therapy.
PMID- 28698068
TI - New nanoparticles obtained by co-assembly of amphiphilic cyclodextrins and
nonlamellar single-chain lipids: Preparation and characterization.
AB - This work aimed at preparing new nanoscale assemblies based on an amphiphilic bio
esterified beta-cyclodextrin (beta-CD), substituted at the secondary face with n
decanoic fatty acid chains (beta-CD-C10), and monoolein (MO) as new carriers for
parenteral drug delivery. Stable binary (beta-CD-C10/MO) and ternary (beta-CD
C10/MO/stabilizer) nanoscale assemblies close to 100nm in size were successfully
prepared in water by the solvent displacement method. The generated nanoparticles
were fully characterized by dynamic light scattering, transmission electron
microscopy, small-angle X-ray scattering, residual solvent analysis, complement
activation and the contribution of each formulation parameter was determined by
principal component analysis. The beta-CD-C10 units were shown to self-organize
into nanoparticles with a hexagonal supramolecular packing that was significantly
modulated by the molar ratio of the constituents and the presence of a steric or
electrostatic stabilizer (DOPE-PEG2000 or DOPA/POPA, respectively). Indeed,
nanoparticles differing in morphology and in hexagonal lattice parameters were
obtained while the co-existence of multiple mesophases was observed in some
formulations, in particular for the beta-CD-C10/MO/DOPA and beta-CD-C10/MO/POPA
systems. The mixed beta-CD-C10/MO/DOPE-PEG2000 nanoparticles (49:49:2 in mol%)
appeared to be the most suitable for use as a drug delivery system since they
contained a very low amount of residual solvent and showed a low level of
complement C3 activation.
PMID- 28698069
TI - Theranostic and nanotheranostic probes in nuclear medicine.
AB - In nuclear medicine, a theranostic probe describes a substance that combines
diagnostic and therapeutic capabilities by radiolabeling it with different
radionuclides. Next to a brief description of the different emitters (alpha,
beta+, beta-, gamma) used for imaging and/or therapy, the aim of this review is
to summarize the most commonly used theranostic probes in nuclear medicine.
Another goal is to give an idea which chemical requirements need to be fulfilled
for radiolabeling with either therapeutic and/or diagnostic relevant nuclides.
Furthermore, a perspective is given into the field of nanotheranostics which is
gaining more and more attention in nuclear medicine. The combination has been
called radionanomedicine and is a very proliferative field with an enormous
potential.
PMID- 28698071
TI - Bilateral plication of the puborectal muscles: A new surgical concept for
treating vulvar widening.
AB - OBJECTIVES: This study describe a new myorraphy technique by bilateral plication
of the puborectalis bundles (PRP) of the levator ani muscle to treat vulvovaginal
widening. The aim of this work was to report our preliminary experience in terms
of morbidity and results (anatomical and functional) in the short and medium
term. MATERIALS AND METHODS: This single centre retrospective study concerned 69
women who underwent PRP between January 2011 and December 2014. The main
criterion for judging success was the GH before and after surgery (Genital Hiatus
in the POP-Q classification: Pelvic Organ Prolapse Quantification System). The
secondary criteria were the quality of sexual intercourse and the morbidity.
RESULTS: The average GH post-surgery was 31, 35 and 35mm at 6 weeks, 6 and 12
months respectively compared to 65+/-5mm preoperatively (P<0.00001). Among the 27
patients who were sexually active prior to surgery, 18.52% deemed the quality of
sexual intercourse satisfactory. After surgery, more than 88% of the patients
observed an improvement (P<0.00001). After the surgery the reported rate of minor
complications was under 3%. CONCLUSION: This preliminary study of PRP confirms
the feasibility of the procedure, its low morbidity and the stability of the
anatomical outcomes at 12 months.
PMID- 28698070
TI - Surgical preparation of rats and mice for intravital microscopic imaging of
abdominal organs.
AB - Intravital microscopy is a powerful research tool that can provide insight into
cellular and subcellular events that take place in organs in the body. However,
meaningful results can only be obtained from animals whose physiology is
preserved during the process of microscopy. Here I discuss the importance of
preserving the overall state of health of the animal, methods of anesthesia,
surgical techniques for intravital microscopy of various abdominal organs,
methods to maintain and monitor the physiology of the animal during microscopy
and associated peri- and post-operative recovery considerations.
PMID- 28698072
TI - Mandatory colposcopic findings of severe cervical dysplasia. Are there key-signs
that need our special attention?
AB - INTRODUCTION: To test for colposcopic differences between CIN2+ and non CIN2+
lesions of the "major changes" of the RIO 2011 nomenclature of the International
Federation of Cervical Pathology (IFCPC). MATERIAL AND METHODS: Retrospective
cohort analysis of colposcopic examinations of patients with histologically
confirmed CIN2+ (n=99) and non CIN2+ (n=102) lesions during a four years period.
MAIN OUTCOME MEASURES: leukoplakia, coarse mosaic and punctuation, dense
acetowhitening, sharp boarders, ridge sign, atypical vessels. RESULTS: Only
coarse punctuation (P<=0.001; OR 9.64; 95% CI 2.15-43.13), coarse mosaic
(P<=0.001; OR 4.00; 95% CI 1.83-8.73) and dense acetowhitening (P<=0.05; OR 1.86;
95% CI 1.06-3.26) occurred more frequently in CIN2+ lesions which were confirmed
as predictors by a regression analysis. CONCLUSIONS: Only coarse punctuation and
coarse mosaic followed by dense acetowhitening as part of the "major changes" of
the IFCPC Rio 2011 nomenclature achieve predictive values for CIN2+ lesions and
should be therefore emphasized in colposcopy.
PMID- 28698073
TI - Does a body mass index greater than 25kg/m2 increase maternal and neonatal
morbidity? A French historical cohort study.
AB - OBJECTIVES: To evaluate, in a French multicenter cohort, the risk of C-section
based on a high pre-pregnancy body mass index (BMI). Secondary objectives were to
assess the risk of elective C-section, severe post-partum hemorrhage (>1L),
severe perineal tears (3rd and 4th degree) and neonatal complications according
to pre-pregnancy BMI. STUDY DESIGN: This historical cohort study analyzed records
from the French AUDIPOG perinatal database. Inclusion criteria were
deliveries>=22 weeks (or with a birth weight>=500g). Women with BMI<18.5kg/m2
(n=31,766) were excluded. After these exclusions, the study sample included
314,851 women between 1999 and 2009. Patients were classified among four BMI
subgroups (normal: 18.5-24.9kg/m2, overweight: 25-29.9kg/m2, class I and II
obesity: 30-39.9kg/m2 and class III obesity:>=40kg/m2). BMI was calculated using
pre-pregnancy self-reported weight. Results were expressed as crude and adjusted
relative risks (aRR). RESULTS: A C-section occurred in 16.4%, 22.7%, 28.8% and
39.4% of normal BMI, overweight, obese and class III obese women, respectively
(P<10-4). aRR of C-section increased with BMI: 1.26 [95%CI: 1.22-1.30] for BMI
between 25-29.9kg/m2; 1.39 [95%CI: 1.34-1.45] for BMI between 30-39.9kg/m2 and
1.72 [95%CI: 1.57-1.90] for BMI>=40kg/m2; but not the elective C-section.
Neonatal complications were more frequent with increasing maternal BMI (BMI 25
29.9: aRR=1.09 [95%CI: 1.06-1.12]; BMI 30-39.9: aRR=1.20 [95%CI: 1.16-1.25];
BMI>=40: aRR=1.33 [95%CI: 1.21-1.45]). CONCLUSION: Our study confirmed that pre
pregnancy BMI is an important factor to consider because its elevation is
associated with adverse obstetrical outcomes, especially cesarean delivery and
neonatal complications.
PMID- 28698074
TI - Fertiloscopy improves in vitro fertilization for women with repeated implantation
failure.
AB - OBJECTIVE: To assess the effects of fertiloscopy procedure on the outcomes of
subsequent in vitro fertilization cycles in patients with repeated implantation
failure (RIF). METHODS: A retrospective study was performed on 50 patients
underwent fertiloscopy and 41 controls with RIF. Pelvic and intrauterine
pathologies related to infertility, clinical pregnancy rate (CPR) and ongoing
pregnancy rate (OPR) of subsequent IVF cycles were assessed. RESULTS: Twenty-six
out of 50 patients (52%) had abnormal fertiloscopic findings. The women who
underwent fertiloscopy exhibited significantly increased CPRs (46.8% vs. 24.4%)
and OPRs (36.2% vs. 12.2%) compared with the control subjects who did not undergo
fertiloscopy. CONCLUSION: The incidence of pathologic findings on fertiloscopy is
high among patients with RIF. Fertiloscopy is valuable in subsequent cycles among
patients with RIF.
PMID- 28698075
TI - Comparison of metformin and N-acetyl cysteine, as an adjuvant to clomiphene
citrate, in clomiphene-resistant women with polycystic ovary syndrome.
AB - OBJECTIVE: To evaluate the effects of short- and long-term treatment with
metformin and NAC, in an adjuvant to clomiphene citrate (CC), on the improvement
of hormonal profile (SHBG, total testosterone, FBS, and fasting insulin) and
fertility status in CC-resistant women with PCOS. MATERIALS AND METHODS: One
hundred and eight CC-resistant PCOS patients participated in the study and
received either metformin (1500mg/day) or NAC (1800mg/day) with 100mg/day of CC
for 8 and 12 weeks. Mean BMI, hirsutism score, LH/FSH ratio, endometrial
thickness, mature follicle number, and serum concentrations of LH, FSH, E2,
fasting insulin, total testosterone and FBS were evaluated before and after short
and long-term treatment. Furthermore, ovulation and pregnancy rates in the first
and second cycles were also determined in treated patients. RESULTS: There was no
significant difference in all variables before and 8 weeks after treatment with
metformin and NAC. The BMI- and insulin-lowering effects of metformin were
significantly higher than NAC after long-term treatment. However, the reducing
effect of NAC on hirsutism score and FBS levels was significantly more than
metformin after 12 weeks. Treatment with metformin and NAC significantly
increased ovulation and pregnancy rates in CC-resistant PCOS patients. In the
first and second cycles, ovulation and pregnancy rates in patients treated with
NAC were slightly higher than those received metformin. CONCLUSIONS: Compared
with metformin, administration of NAC in an adjuvant to CC is recommended for
improving of hormonal profile and treatment of anovulatory infertility in
hyperinsulinemic patients especially women with PCOS who are CC-resistant.
PMID- 28698076
TI - Synthesis and characterization of chitosan-PVP-nanocellulose composites for in
vitro wound dressing application.
AB - Biocompatible Chitosan/Poly (vinyl pyrrolidone)/Nanocellulose (CPN) composites
were successfully prepared by solution casting method. The prepared
bionanocomposites were characterized by Transmission electron microscopy (TEM),
Thermo gravimetric analysis (TGA), X-ray diffraction (XRD) and Attenuated total
reflectance-Fourier transform infrared spectroscopy (ATR-FTIR) spectra. TEM
images revealed the average particle size of the nanocellulose is 6.1nm.
Thermogravimetric analysis indicated that the thermal stability of the composites
was decreased with increasing concentration of nanocellulose. The CPN composites
were characterized for physical properties like Thickness, Barrier properties and
mechanical testing. Water vapor and oxygen permeability evaluations indicated
that CPN composite could maintain a moist environment over wound bed. The
nanocomposite showed enhanced swelling, blood compatibility and antibacterial
activity. Cytotoxicity of the composite has been analyzed in normal mouse
embryonic fibroblast cells. The results have shown the CPN3% composite shows a
high level of antibacterial property when compared to the other composites. The
biological study suggests that CPN3% composite may be a potential candidate as a
wound healing material for biomedical application.
PMID- 28698077
TI - Examination of In vitro and In vivo biocompatibility of alginate-hyaluronic acid
microbeads As a promising method in cell delivery for kidney regeneration.
AB - In this study, alginate (ALG) and alginate-hyaluronic acid (ALG-HA) injectable
microbeads, with the purpose of delivering stem cells for tissue engineering,
were prepared by a spraying method into a CaCl2 solution that shows high porosity
for the exchange of nutrition and waste. In addition, the size distribution and
surface morphology was investigated using optical and scanning electron
microscopy, respectively. The chemical structural properties of the ALG-HA
microbeads were examined by Fourier transform infrared spectroscopy. The
biocompatibility of ALG and ALG-HA microbeads was examined in vitro. Rat bone
marrow stem cells were encapsulated in microbeads to investigate cell release,
cell viability, proliferation, and secretion of growth factors such as VEGF and
PDGF. Growth factors were released for the 21day experimental period. Cells were
found to be released from the microbeads after 7days. Furthermore, the in vivo
biocompatibility of ALG-HA microbeads was examined using microbeads without cell
encapsulation in the kidney capsule, in order to assess the foreign body reaction
and inflammatory response, for 14days. The desired in vivo response to ALG-HA
microbeads hydrogel makes it an exquisite candidate for subcapsular cell and drug
delivery to kidney tissue.
PMID- 28698078
TI - Chitosan nanofilm and electrospun nanofiber for quick drug release in the
treatment of Alzheimer's disease: In vitro and in vivo evaluation.
AB - Chitosan micro sized ODF (CBF), chitosan nano sized ODF (CNF) and chitosan
nanofiber (CNfib) were prepared to release the donepezil drug quickly for
Alzheimer's disease. CNF and CNfib were prepared from ionic gelation technique
and electro-spinning process which were further examined under in vitro and in
vivo animal model studies. Good thermal stability of CNfib (450 degrees C) when
compared to CBF (325 degrees C) and CNF (305 degrees C). The particle size was
below 150nm in diameter for CNfib and 250nm in diameter for CNF4 from TEM
technique. In vitro antimicrobial activities for ODF and nanofibers were
conducted by well diffusion method against Gram +ve and Gram -ve bacteria after
24h of incubation. From the in vitro release profile, the CNfib was competently
showed rapid release of drug up to 97% than the thin film of CBF2 and CNF4
respectively in the initial period of 10min. In vivo animal model studies
demonstrated that the drug reached the maximum concentration within 3.5h for
chitosan nanofiber and nanofilm (CNF4). The chitosan nanofiber has given
significantly faster absorption rate [1860.5ng/ml of AUC(0-infinity)] and the
mean total area under curve was 161.71% on contrasted with chitosan nanofilm
(CNF4).
PMID- 28698079
TI - Purification and fermentation characteristics of exopolysaccharide from
Fomitopsis castaneus Imaz.
AB - Short-chain fatty acids (SCFAs), which are the end products of carbohydrate
fermentation in the gut, mainly contribute to energy metabolism in mammals. The
amount of SCFAs produced during fermentation is an important parameter that
characterizes the fermentation capacity of a system. This paper reports on the
fermentation characteristics of exopolysaccharides (EPS) isolated from Fomitopsis
castaneus Imaz, a wood-rot fungal species. We isolated and purified the main EPS
fraction by freeze drying and DEAE-Sepharose fast flow chromatography. We then
analyzed the monosaccharide composition of EPS. The isolated EPS was mainly
composed of glucose, galactose, rhamnose, mannose, and arabinose. The
characteristic absorption peaks of sugar esters were also detected. Fresh fecal
extracts from healthy adults and children were used as fermentation substrate to
simulate the human intestinal environment (anaerobic conditions at 37 degrees C)
and study the fermentation characteristics of the purified EPS. Adding the
isolated EPS to the fermentation system of the simulated intestinal environment
increased the SCFAs content in the fecal extract of adults and children. However,
the yield of SCFAs, particularly butyric acid, in the fermentation system of
fecal extract in children was higher than that in adults. Furthermore, adding
exogenous lactic acid bacteria, such as Enterococcus fecalis and Enterococcus
fecium, to the fermentation system effectively increased the SCFAs concentration
in the model intestinal system of the children. By contrast, adding E. fecalis,
Lactobacillus rhamnosus, and E. fecium increased the content of the produced
SCFAs in the system of adults. Those results indicate that EPS isolated from F.
castaneus Imaz was effectively fermented in the simulated intestinal
environments, and the fermentation capability was enhanced by adding microbial
flora.
PMID- 28698080
TI - The complete mitochondrial genome of Euproctis similis (Lepidoptera: Noctuoidea:
Erebidae) and phylogenetic analysis.
AB - The mitochondrial genome (mitogenome) can provide information for phylogenetic
analyses and evolutionary biology. We sequenced, annotated, and characterized the
mitogenome of Euproctis similis. The complete mitogenome is 15,437bp in length,
containing 13 protein-coding genes (PCGs), 22 transfer RNA genes, two ribosomal
RNA genes, and a control region (A+T-rich region). The A+T content in the
mitogenome was 80.16%. All PCGs use standard ATN as a start codon, with the
exception of cytochrome c coxidase 1 (cox1) with CGA. A gene rearrangement (trnM)
was found. All transfer RNA (tRNA) genes have a typical clover-leaf structure
except for trnS1 (AGN). Phylogenetic analysis was performed using Bayesian
Inference and Maximum Likelihood based on the amino acid and nucleotide sequences
of 13 mitochondrial PCGs. The well-supported phylogenetic relationships can be
generally described as: Notodontidae+(Erebidae+(Nolidae+(Euteliidae+Noctuidae))).
The tree support that E. similis shares a close ancestry with Erebidae insects.
Our results indicate that Erebidae is a sister group to the other families
(Euteliidae, Nolidae, and Noctuidae).
PMID- 28698081
TI - In vitro immunological and anti-complementary activities of two water-soluble
lignins from Zizyphus jujube cv. Jinchangzao.
AB - Two homogenous biological macromolecules, designated as JJC1 and JJC2 were
extracted from Zizyphus jujube cv. Jinchangzao. Their molecular weights were
determined to be 56.03 and 112.11kDa by high performance gel permeation
chromatography (HPGPC), respectively. Chemical and spectral analysis indicated
that both JJC1 and JJC2 mainly consisted of lignin, along with carbohydrates
(~18%). Both JJC1 and JJC2 could stimulate the proliferation of spleen
lymphocytes, and enhance phagocytosis and NO production of RAW264.7 cells. In
addition, JJC2, but not JJC1 elicited an inhibitory effect on complement
activation through the classical pathway (CH50: 2.73mg/mL) as well as the
alternative pathway (AP50: 2.99mg/mL). These findings implied that water-soluble
lignins were one of the bioactive components in Z. jujube, and further provided
insights into the understanding of molecular basis for diverse medicinal and
nutritional values of this fruit.
PMID- 28698082
TI - Mechanisms of facial emotion recognition in autism spectrum disorders: Insights
from eye tracking and electroencephalography.
AB - While behavioural difficulties in facial emotion recognition (FER) have been
observed in individuals with Autism Spectrum Disorder (ASD), behavioural studies
alone are not suited to elucidate the specific nature of FER challenges in ASD.
Eye tracking (ET) and electroencephalography (EEG) provide insights in to the
attentional and neurological correlates of performance, and may therefore provide
insight in to the mechanisms underpinning FER in ASD. Given that these processes
develop over the course of the developmental trajectory, there is a need to
synthesise findings in regard to the developmental stages to determine how the
maturation of these systems may impact FER in ASD. We conducted a systematic
review of fifty-four studies investigating ET or EEG meeting inclusion criteria.
Findings indicate divergence of visual processing pathways in individuals with
ASD. Altered function of the social brain in ASD impacts the processing of facial
emotion across the developmental trajectory, resulting in observable differences
in ET and EEG outcomes.
PMID- 28698083
TI - A Hemorrhagic Clival Chordoma with a Long Progression-Free Survival.
AB - BACKGROUND: Chordomas and ecchordosis physaliphora may on rare occasions present
with intracranial hemorrhage. Their distinction usually relies on the results of
the Ki-67 proliferative index, with a result lower than 1% favoring ecchordosis
physaliphora. Intracranial hemorrhagic chordomas have been linked to unfavorable
prognosis, due to acute neurologic deterioration and death, or progression after
treatment. To the best of our knowledge, this is the first report of a patient
with an intracranial hemorrhagic chordoma who had a long progression-free
survival. CASE DESCRIPTION: A 67-year-old woman presented with a large
hemorrhagic clival tumor that was resected through an endonasal endoscopic
approach. Physallipharous cells interspersed in a myxoid matrix, positivity for S
100, cytokeratin, and epithelial membrane antigen were found, along with an
extremely low Ki-67 index. Imaging findings of bone erosion, a large size, and
enhancement favored the diagnosis of chordoma. The patient received adjuvant
stereotactic radiotherapy and has remained disease free after 4 years.
CONCLUSIONS: Although hemorrhagic intracranial chordomas have been linked to
unfavorable outcomes, our case demonstrates that they may have a low
proliferative index, and a long progression-free survival may be seen.
PMID- 28698084
TI - Endoscopic Submandibular Retropharyngeal Approach to the Craniocervical Junction
and Clivus: an Anatomic Study.
AB - INTRODUCTION: Surgery of the craniocervical junction (CCJ) and clivus is
technically demanding. For many years, we have used the submandibular
retropharyngeal approach for surgery of the upper cervical spine, especially
hangman fracture. We hypothesized that submandibular gland resection could offer
a significant cranial enlargement of the operative field, up to the clivus. Our
aim in this work was to assess the feasibility of an endoscope-assisted
retropharyngeal approach to the CCJ and clivus. METHODS: Eight anatomic specimens
were used, including 4 silicon-injected specimens. We performed a submandibular
retropharyngeal approach with gland resection, and then we exposed the CCJ and
clivus. We drilled the C2 vertebral body, odontoid process, C1 anterior arch, and
the clivus. We noted 8 anatomic landmarks that were easily identified on each
anatomic specimen. These measurements were designed to quantify the exposure of
the clivus and CCJ after bone resection. RESULTS: A submandibular approach was
feasible in all specimens. The main dimensions of the area of dural exposure
after bone drilling were as follows: mean width between C1 lateral masses, 19 mm
(range, 17-20 mm); at the tip of the clival window, 18 mm (range, 16-20 mm);
distance between the C3 vertebra and the tip of the window within the clivus, 57
mm (range, 55-60 mm). CONCLUSIONS: An endoscopic submandibular retropharyngeal
approach provides a simple and straightforward access to the CCJ. It also
conveniently exposes the clivus. This technique could be added to the techniques
used for this difficult surgery.
PMID- 28698085
TI - Modified Park Bench Position for Superior Vermian Arteriovenous Malformations and
Dural Fistulas.
AB - OBJECTIVES: Arteriovenous malformations (AVMs) of the superior cerebellar vermis
and dural arteriovenous fistulas (dAVFs) draining into tentorial venous
structures are uncommon lesions. Various surgical approaches and positions have
been used to gain access. METHODS: We present our experience with 10 superior
vermian AVMs and 3 dAVFs with retrograde transverse sinus or torcular drainage,
each resected through a supracerebellar infratentorial approach in the park bench
position with modification of the neck and head position (vertex tilt-up instead
of down). RESULTS: All 13 patients were treated surgically, with 4 receiving
adjunctive endovascular embolization. Postoperative digital subtraction
angiography confirmed complete resection of lesion in all. One patient
experienced superficial wound infection treated by oral antibiotics, and another
presented with a cerebrospinal fluid collection due to delayed hydrocephalus
requiring insertion of a ventriculoperitoneal shunt. The median modified Rankin
Scale score at last follow-up was 1. There were no surgical complications at the
time of last follow-up. CONCLUSIONS: Our series shows that for superior vermian
AVMs or dAVFs with retrograde transverse sinus or torcula venous drainage, the
supracerebellar infratentorial approach in a modified vertex tilt-up park bench
position is a safe and effective surgical approach.
PMID- 28698086
TI - Stroke Burden in Rwanda: A Multicenter Study of Stroke Management and Outcome.
AB - BACKGROUND: Cerebrovascular accidents or stroke constitute the second leading
cause of mortality worldwide. Low- and middle-income countries bear most of the
stroke burden worldwide. The main objective of this study is to determine the
burden of stroke in Rwanda. METHODS: This was a prospective observational study
in 2 parts: 6 months baseline data collection and outcome assessment sessions at
1 year. RESULTS: A total of 96 patients were enrolled in our series. Stroke
constituted 2100 per 100,000 population. Of all patients, 55.2% were male and
most (60%) were 55 years and older. Of all patients and/or caretakers, 22% were
not aware of their previous health status and 53.5% of hypertensive patients were
not on treatment by the time of the event. Median presentation delay was 72 hours
for patients with ischemic stroke and 24 hours for patients with hemorrhagic
stroke. Most patients had hemorrhagic stroke (65% vs. 35%), and more patients
with hemorrhagic stroke presented with loss of consciousness (80% vs. 51%). Many
patients (62% ischemic group and 44% hemorrhagic group) presented with severe
stroke scores, and this was associated with worst outcome (P = 0.004). At 1 year
follow-up, 24.7% had no or mild disability, 14.3% were significantly disabled,
and 61% had died. CONCLUSIONS: Our results show that stroke is a significant
public health concern in Rwanda. Risk factor awareness and control are still low
and case fatality of stroke is significantly high. The significant delay in
presentation to care and presentation with severe stroke are major contributors
for the high mortality and severe disability rates.
PMID- 28698087
TI - Computational Fluid Dynamics Simulation of Hemodynamic Alterations in Sigmoid
Sinus Diverticulum and Ipsilateral Upstream Sinus Stenosis After Stent
Implantation in Patients with Pulsatile Tinnitus.
AB - OBJECTIVE: To investigate the relationships between upstream venous sinus
stenosis and pulsatile tinnitus (PT), and to assess the correlation with
diverticulum growth and the effectiveness of stent implantation. METHODS: Patient
specific geometric models were constructed using computed tomography venography
images from a patient with PT, with sigmoid sinus diverticulum, and with upstream
transverse sinus stenosis, in whom stenting of the upstream sinus stenosis alone
achieved complete remission of PT. Computational fluid dynamics simulation based
on this patient-specific geometry was performed using commercially available
finite element software (ANSYS-14) to qualitatively and quantitatively compare
the flow velocity, flow rate, velocity vector, pressure, vorticity, and wall
shear stress on the affected side transverse and sigmoid sinuses, before and
after stent implantation. RESULTS: Stenting improved the flow direction and
magnitude. After stenting, the flow pattern became smoother and more regular.
High-speed blood flow at the level of the diverticulum neck was confined to a
smaller area, and its direction changed from approximately perpendicular to the
diverticular dome to the distal side of the diverticular neck. The diverticulum
showed obvious flow reduction, with decreases of 80.7%, 68.7%, 96.1%, and 91.3%
in peak velocity, inflow rate, pressure gradient, and peak vorticity,
respectively. The abnormally low wall shear stress at the dome of diverticulum
was eliminated. CONCLUSIONS: Our findings strongly support a major role of
diverticulum stenosis before in PT development and suggest that such stenosis is
a causative factor of diverticulum growth. They also confirm the effectiveness of
stent implantation for the treatment of PT.
PMID- 28698088
TI - Microsurgical Repair of Ruptured Aneurysms Associated with Moyamoya-Pattern
Collateral Vessels of the Middle Cerebral Artery: A Report of Two Cases.
AB - BACKGROUND: Patients with Moyamoya or other intracranial steno-occlusive disease
are at risk for developing aneurysms associated with flow through collateral
vessels. Because these lesions are rare, the optimal management remains unclear.
Here, we describe 2 cases of microsurgical repair of ruptured collateral vessel
aneurysms associated with middle cerebral artery (MCA) occlusion. CASE
DESCRIPTION: The first patient was a 61-year-old man who presented with right
frontal and intraventricular hemorrhage. Angiography revealed chronic right M1
occlusion and a 3-mm spherical lenticulostriate aneurysm. The frontal lobe
hematoma was evacuated to reveal the aneurysm, which was safely cauterized and
resected by coagulating and dividing the lenticulostriate parent vessel. The
procedure was carried out with neuronavigation guidance and intraoperative
neuromonitoring. The patient was discharged with no neurologic deficits. The
second patient was a 53-year-old woman who presented with subarachnoid and
intracerebral hemorrhage. Computed tomography angiogram showed a 2-mm saccular
MCA aneurysm. Emergency left decompressive hemicraniectomy and hematoma
evacuation were performed. The aneurysm, arising from a small collateral type
vessel, was safely clipped without complications. Postoperative angiography
revealed absence of the superior MCA trunk with a dense network of collateral
vessels at the site of the clipped aneurysm. The patient recovered well and was
ambulating independently 6 months postoperatively. No rebleeding occurred in the
2 patients. CONCLUSIONS: Our experience suggests that patients with MCA occlusion
can harbor associated aneurysms related to flow through collateral vessels and
can present with hemorrhage. Microsurgical repair of these aneurysms can be
performed safely to prevent rebleeding.
PMID- 28698089
TI - Type 2 Diabetes Mellitus and Glioblastoma Multiforme-Assessing Risk and Survival:
Results of a Large Retrospective Study and Systematic Review of the Literature.
AB - OBJECTIVE: Despite studies showing a positive correlation between type 2 diabetes
mellitus (DM2), a modifiable risk factor, and various cancer types, the link
remains controversial in the setting of glioblastoma multiforme (GBM). In this
study, we assessed whether DM2 and DM2-associated factors were associated with a
higher risk of developing GBM and also determined if DM2 affected the survival of
patients with GBM. METHODS: A cross-sectional case-control study of 1144 GBM
cases diagnosed between 2000 and 2013 of which 969 patients matched for age and
sex was performed to assess the association between DM2, hyperlipidemia, and
obesity with the incidence of GBM. A longitudinal study of the patients with GBM
was also performed to assess the association between the effect of DM2 and GBM
survival. RESULTS: No association was seen between DM2, hyperlipidemia, obesity,
and GBM. DM2 was associated with poorer survival in univariate testing yet not in
multivariate testing. Diabetic patients with GBM had good glycemic control. Older
patients had poorer survival and overall survival improved over years of study.
CONCLUSIONS: DM2, hyperlipidemia, and obesity were not associated with increased
risk of developing GBM, and DM2 itself does not seem to influence survival among
these patients. This finding might be related to good glycemic control in this
cohort. Survey of the literature consistently shows that hyperglycemia is
associated with poorer survival. Our findings suggest that rather than the
presence or absence of DM2, glycemic control seems to be more important in the
survival of patients with GBM, which warrants future investigation.
PMID- 28698090
TI - The Superior Frontal Transsulcal Approach to the Anterior Ventricular System:
Exploring the Sulcal and Subcortical Anatomy Using Anatomic Dissections and
Diffusion Tensor Imaging Tractography.
AB - OBJECTIVE: To explore the superior frontal sulcus (SFS) morphology, trajectory of
the applied surgical corridor, and white matter bundles that are traversed during
the superior frontal transsulcal transventricular approach. METHODS: Twenty
normal, adult, formalin-fixed cerebral hemispheres and 2 cadaveric heads were
included in the study. The topography, morphology, and dimensions of the SFS were
recorded in all specimens. Fourteen hemispheres were investigated through the
fiber dissection technique whereas the remaining 6 were explored using coronal
cuts. The cadaveric heads were used to perform the superior frontal transsulcal
transventricular approach. In addition, 2 healthy volunteers underwent diffusion
tensor imaging and tractography reconstruction studies. RESULTS: The SFS was
interrupted in 40% of the specimens studied and was always parallel to the
interhemispheric fissure. The proximal 5 cm of the SFS (starting from the SFS
precentral sulcus meeting point) were found to overlie the anterior ventricular
system in all hemispheres. Five discrete white matter layers were identified en
route to the anterior ventricular system (i.e., the arcuate fibers, the frontal
aslant tract, the external capsule, internal capsule, and the callosal
radiations). Diffusion tensor imaging studies confirmed the fiber tract
architecture. CONCLUSIONS: When feasible, the superior frontal transsulcal
transventricular approach offers a safe and effective corridor to the anterior
part of the lateral ventricle because it minimizes brain retraction and
transgression and offers a wide and straightforward working corridor. Meticulous
preoperative planning coupled with a sound microneurosurgical technique are
prerequisites to perform the approach successfully.
PMID- 28698091
TI - Endothelial cells: From innocent bystanders to active participants in immune
responses.
AB - The endothelium is crucially important for the delivery of oxygen and nutrients
throughout the body under homeostatic conditions. However, it also contributes to
pathology, including the initiation and perpetuation of inflammation.
Understanding the function of endothelial cells (ECs) in inflammatory diseases
and molecular mechanisms involved may lead to novel approaches to dampen
inflammation and restore homeostasis. In this article, we discuss the various
functions of ECs in inflammation with a focus on pathological angiogenesis,
attraction of immune cells, antigen presentation, immunoregulatory properties and
endothelial-to-mesenchymal transition (EndMT). We also review the current
literature on approaches to target these processes in ECs to modulate immune
responses and advance anti-inflammatory therapies.
PMID- 28698092
TI - Spasticity in multiple sclerosis: Contribution of inflammation, autoimmune
mediated neuronal damage and therapeutic interventions.
AB - In contrast to other diseases that go along with spasticity (e.g. spinal cord
injury), spasticity in chronic autoimmune diseases involving the CNS is
complicated by the ongoing damage of neuronal networks that leads to permanent
changes in the clinical picture of spasticity. Multiple sclerosis (MS) is the
most frequent autoimmune disease of the central nervous system (CNS) and
spasticity is one of the most disabling symptoms. It occurs in more than 80% MS
patients at some point of the disease and is associated with impaired ambulation,
pain and the development of contractures. Besides causing cumulative structural
damage, neuroinflammation occurring in MS leads to dynamic changes in motor
circuit function and muscle tone that are caused by cytokines, prostaglandins,
reactive oxygen species and stress hormones that affect neuronal circuits and
thereby spasticity. The situation is complicated further by the fact that
therapeutics used for the immunotherapy of MS may worsen spasticity and drugs
used for the symptomatic treatment of spasticity have been shown to have the
potential to alter immune cell function and CNS autoimmunity itself. This review
summarizes the current knowledge on the immunologic pathways that are involved in
the development, maintenance, dynamic changes and pharmacological modulation of
spasticity in MS.
PMID- 28698093
TI - Bile acids and intestinal microbiota in autoimmune cholestatic liver diseases.
AB - Autoimmune cholestatic liver diseases, including primary biliary cholangitis
(PBC) and primary sclerosing cholangitis (PSC), are manifested as an impairment
of normal bile flow and excessive accumulation of potentially toxic bile acids.
Endogenous bile acids are involved in the pathogenesis and progression of
cholestasis. Consequently, chronic cholestasis affects the expression of bile
acid transporters and nuclear receptors, and results in liver injury. Several
lines of evidence suggest that intestinal microbiota plays an important role in
the etiopathogenesis of cholestatic liver diseases by regulating metabolism and
immune responses. However, progression of the disease may also affect the
composition of gut microbiota, which in turn exacerbates the progression of
cholestasis. In addition, the interaction between intestinal microbiota and bile
acids is not unidirectional. Bile acids can shape the gut microbiota community,
and in turn, intestinal microbes are able to alter bile acid pool. In general,
gut microbiota actively communicates with bile acids, and together play an
important role in the pathogenesis of PBC and PSC. Targeting the link between
bile acids and intestinal microbiota offers exciting new perspectives for the
treatment of those cholestatic liver diseases. This review highlights current
understanding of the interactions between bile acids and intestinal microbiota
and their roles in autoimmune cholestatic liver diseases. Further, we postulate a
bile acids-intestinal microbiota-cholestasis triangle in the pathogenesis of
autoimmune cholestatic liver diseases and potential therapeutic strategies by
targeting this triangle.
PMID- 28698094
TI - Biomarkers of disease activity in vitiligo: A systematic review.
AB - The pathophysiology of vitiligo is complex although recent research has
discovered several markers which are linked to vitiligo and associated with
disease activity. Besides providing insights into the driving mechanisms of
vitiligo, these findings could reveal potential biomarkers. Activity markers can
be used to monitor disease activity in clinical trials and may also be useful in
daily practice. The aim of this systematic review was to document which factors
have been associated with vitiligo activity in skin and blood. A second goal was
to determine how well these factors are validated in terms of sensitivity and
specificity as biomarkers to determine vitiligo activity. Both in skin (n=43) as
in blood (n=66) an adequate number of studies fulfilled the predefined inclusion
criteria. These studies used diverse methods and investigated a broad range of
plausible biomarkers. Unfortunately, sensitivity and specificity analyses were
scarce. In skin, simple histopathology with or without supplemental CD4 and CD8
stainings can still be considered as the gold standard, although more recently
chemokine (C-X-C motif) ligand (CXCL) 9 and NLRP1 have demonstrated a good and
possibly even better association with progressive disease. Regarding circulating
biomarkers, cytokines (IL-1beta, IL-17, IFN-gamma, TGF-beta), autoantibodies,
oxidative stress markers, immune cells (Tregs), soluble CDs (sCD25, sCD27) and
chemokines (CXCL9, CXCL10) are still competing. However, the two latter may be
preferable as both chemokines and soluble CDs are easy to measure and the
available studies display promising results. A large multicenter study could make
more definitive statements regarding their sensitivity and specificity.
PMID- 28698095
TI - Circulating CXCL10 is increased in non-segmental vitiligo, in presence or absence
of autoimmune thyroiditis.
AB - Recently the importance of CXCL10 in the pathogenesis of non-segmental vitiligo
(NSV) and autoimmune thyroid disorders (AITD) has been shown. No data are present
about chemokines CXCL10 (Th1 prototype) and CCL2 (Th2 prototype) circulating
levels in NSV patients with/without thyroiditis (AT). Serum CXCL10 and CCL2 have
been measured in 50 consecutive NSV patients, in 40 consecutive patients with NSV
and AT (NSV+AT), in 50 sex- and age-matched controls without AT (control 1) and
in 40 sex- and age-matched patients with AT without NSV (control 2). Serum CXCL10
levels were significantly higher in control 2, than in control 1 (P=0.001;
ANOVA). NSV patients have serum CXCL10 levels significantly higher than control
1, or control 2 (P=0.001). NSV+AT patients have serum CXCL10 levels higher than
control 1, or 2 (P<0.001), and than NSV (P=0.01). In conclusion, we first
demonstrate high serum CXCL10 in NSV patients, overall in presence of AT and
hypothyroidism, suggesting the importance of a common Th1 immune response in
their immune-pathogenesis. To evaluate if serum CXCL10 might be used as a
clinical marker of NSV and/or AT further studies are needed.
PMID- 28698096
TI - Differential pulmonary effects of wintertime California and China particulate
matter in healthy young mice.
AB - Airborne particulate matter (PM) is associated with adverse cardiorespiratory
effects. To better understand source-orientated PM toxicity, a comparative study
of the biological effects of fine PM (diameter<=2.5MUm, PM2.5) collected during
the winter season from Shanxi Province, China, and the Central Valley,
California, United States, was conducted. The overarching hypothesis for this
study was to test whether the chemical composition of PM on an equal mass basis
from two urban areas, one in China and one in California, can lead to
significantly different effects of acute toxicity and inflammation in the lungs
of healthy young mice. Male, 8-week old BALB/C mice received a single 50MUg dose
of vehicle, Taiyuan PM or Sacramento PM by oropharyngeal aspiration and were
sacrificed 24h later. Bronchoalveolar lavage, ELISA and histopathology were
performed along with chemical analysis of PM composition. Sacramento PM had a
greater proportion of oxidized organic material, significantly increased
neutrophil numbers and elevated CXCL-1 and TNF-alpha protein levels compared to
the Taiyuan PM. The findings suggest that Sacramento PM2.5 was associated with a
greater inflammatory response compared to that of Taiyuan PM2.5 that may be due
to a higher oxidice. Male, 8-week old BALB/C mice received a single 50MUg dose of
vehicle, Taiyuan PM or Sacramento PM by oropharyngeal aspiration and were
sacrificed 24h later. Bronchoalveolar lavage, ELISA and histopathology were
performed along with chemical analysis of PM composition. Sacramento PM had a
greater proportion of oxidized organic material, significantly increased
neutrophil numbers and elevated CXCL-1 and TNF-alpha protein levels compared to
the Taiyuan PM. The findings suggest that Sacramento PM2.5 was associated with a
greater inflammatory response compared to that of Taiyuan PM2.5 that may be due
to a higher oxidized state of organic carbon and copper content.
PMID- 28698097
TI - Enzymatic reactive oxygen species assay to evaluate phototoxic risk of
metabolites.
AB - The present study aimed to verify the feasibility of an enzymatic reactive oxygen
species (eROS) assay to evaluate the phototoxic risk of compounds after their
metabolization. The eROS assay was designed based on the combined use of an in
vitro drug metabolism system and a ROS assay. The incubation time of compounds
with human hepatic S9 fractions was optimized with the use of fenofibrate (FF), a
typical phototoxicant with metabolite-related phototoxicity, and the
reproducibility and robustness of the eROS assay were examined using FF. The eROS
assay was applied to 12 phototoxic compounds, including 7 phototoxicants with
metabolite-related phototoxicity, to clarify the assay performance. According to
the eROS data on singlet oxygen generation from FF and metabolic conversion
profiles of FF and fenofibric acid, the incubation time of chemicals with human
hepatic S9-mix was determined to be 4min. The singlet oxygen-based evaluation
system in the eROS assay was found to be acceptable as a high-throughput assay
because of its favorable intra-/inter-day reproducibility (coefficient of
variation: ca. 8%) and robustness (Z'-factor: 0.23). Singlet oxygen data on
phototoxicants with phototoxic metabolites tended to exceed 120% of control,
suggesting the feasibility of the eROS assay to evaluate metabolite-related
phototoxic potentials. However, further data accumulation is still needed to
improve the assay performance because the eROS assay provided false predictions
for some compounds. The present eROS assay may be applicable in part for
evaluating the phototoxic risk of drug candidates after their metabolization in
the early stage of drug discovery.
PMID- 28698098
TI - Development of a single-cell GlxR-based cAMP biosensor for Corynebacterium
glutamicum.
AB - Cyclic adenosine monophosphate (cAMP) plays a regulatory role as second messenger
in many species. In the industrial model organism Corynebacterium glutamicum,
cAMP acts as effector of the global transcriptional regulator GlxR, a homolog of
enterobacterial Crp. The cAMP-GlxR complex activates or represses the expression
of about 200 target genes. CyaB, a membrane-bound class III adenylate cyclase,
synthesizes cAMP from ATP, but another yet unknown cAMP-forming enzyme is likely
present in C. glutamicum. Recently, we identified the cAMP phosphodiesterase
CpdA, which catalyzes the conversion of cAMP to AMP. As a tool to search for
additional cAMP-forming and degrading enzymes, we constructed a plasmid-based
cAMP biosensor by fusing the promoter of cg3195, a gene strongly repressed by
GlxR, to the eyfp reporter gene. In control experiments, the biosensor showed the
predicted responses to increased levels of cAMP or GlxR. The biosensor was able
to distinguish between C. glutamicum wild type and mutants with defects in cAMP
biosynthesis or degradation. Most importantly, the sensor allowed successful
sorting of mixtures of wild type and mutant strains by fluorescence activated
cell sorting (FACS), thus meeting the requirements for high-throughput screening
of libraries for single mutant cells with an altered cAMP level.
PMID- 28698099
TI - Bioinformatics in the plant genomic and phenomic domain: The German contribution
to resources, services and perspectives.
AB - Plant genetic resources are a substantial opportunity for plant breeding,
preservation and maintenance of biological diversity. As part of the German
Network for Bioinformatics Infrastructure (de.NBI) the German Crop
BioGreenformatics Network (GCBN) focuses mainly on crop plants and provides both
data and software infrastructure which are tailored to the needs of the plant
research community. Our mission and key objectives include: (1) provision of
transparent access to germplasm seeds, (2) the delivery of improved workflows for
plant gene annotation, and (3) implementation of bioinformatics services that
link genotypes and phenotypes. This review introduces the GCBN's spectrum of web
services and integrated data resources that address common research problems in
the plant genomics community.
PMID- 28698100
TI - Adenosquamous gallbladder carcinoma: Multigene hotspot mutational profiling
reveals a monoclonal origin of the two components.
AB - Adenosquamous carcinoma (ASC) of the gallbladder is a rare malignant tumor that
is characterized by a coexisting of glandular and squamous components. In a case
of ASC, we performed hotspot multigene mutational profiling of 164 hotspot
regions of eleven cancer-associated genes (AKT1, APC, BRAF, CTNNB1, KIT, KRAS,
NRAS, PDGFRA, PIK3CA, PTEN and TP53) in the two microdissected components. Both
tumor phenotypes resulted characterized by a p.E542K point mutation in the PIK3CA
gene, whereas adenocarcinoma component revealed also a TP53 Q331* homozygous stop
mutation. Of note, coexisting high-grade dysplastic epithelium was characterized
by a mixed cell population, with an upper part featuring a glandular
differentiation and a basal layer of p63 positive (squamous committed) cells.
Overall these data provide evidence of an early squamous differentiation of the
lesion with a common genetic landscape of the two components.
PMID- 28698101
TI - Coenzyme Q10 ameliorates cerebral ischemia reperfusion injury in hyperglycemic
rats.
AB - The purpose of this study is to investigate the effect of coenzyme Q10 (CoQ10) on
focal cerebral ischemia/reperfusion (I/R) injury in hyperglycemic rats and the
possible involved mechanisms. In this study, we established the transient middle
cerebral artery occlusion (MCAO) for 30min in the rats with diabetic
hyperglycemia. The neurological deficit score, 2,3,5-triphenyltetrazolium
chloride (TTC) staining and pathohistology are applied to detect the extent of
the damage. The expression of Fis1, Mfn2 and Lc3 in the brain is investigated by
immunohistochemical and Western blotting techniques. The results showed that the
streptozotocin-induced diabetic hyperglycemia and MCAO-induced focal cerebral
ischemia were successfully prepared in rats. In the hyperglycemic group, the
neurological deficit scores, infarct volumes, and number of pyknotic cells were
higher than that in the normalglycemic group at 24h and/or 72h reperfusion.
Pretreated with CoQ10 (10mg/kg) for four weeks could significantly reduce the
neurological scores, infarct volume, and pyknotic cells at 24h and/or 72h
reperfusion of the hyperglycemic rats compared with non-CoQ10 pretreated
hyperglycemic animals. Immunohistochemistry and Western blotting showed that
pretreatment with CoQ10 or insulin could significantly reduce the expression of
Fis1 protein in the brain at 24h and 72h reperfusion. Inversely, a significantly
increased expression of Mfn2 was observed in the rats CoQ10 or insulin pretreated
at 24h and/or 72h reperfusion when compared with matched hyperglycemic rats.
These results demonstrated that hyperglycemia could aggravate ischemic brain
injury. Pretreatment with CoQ10 might ameliorate the diabetic hyperglycemia
aggravated I/R brain damage in the MCAO rats by maintain the balance between
mitochondrial fission and fusion.
PMID- 28698102
TI - Neonatal Nav1.5 protein expression in normal adult human tissues and breast
cancer.
AB - Expression of the neonatal splice variant of the voltage-gated sodium channel
alpha-subunit (VGSC) subtype Nav1.5 (nNav1.5), encoded by the gene SCN5A, was
shown earlier to be upregulated in human breast cancer (BCa), both in vitro and
in vivo. Channel activity promoted BCa invasion of Matrigel(r)in vitro and
metastasis in vivo. Consequently, expression of nNav1.5 has been proposed as a
functional biomarker of BCa cells with metastatic potential. Here, we have
determined immunohistochemically both nNav1.5 and total VGSC (tVGSC) protein
expression in a range of adult human tissues. Some VGSC protein was expressed in
normal colon, small intestine, stomach, prostate, bladder and breast. As
expected, high levels of VGSC protein were expressed in brain, skeletal muscle
and cardiac muscle. On the other hand, nNav1.5 protein was not expressed in any
of the normal tissues tested except breast where a low-level of protein was
present. In comparison to normal breast, nNav1.5 protein expression in BCa was
consistently widespread and occurred at a significantly higher level. We also
questioned whether there was any relationship between the nNav1.5 protein
expression and the estrogen receptor (ERalpha) status of BCa and obtained the
following results. First, all cases lacking nNav1.5 were positive for ERalpha.
Second, in all ERalpha-negative tissues, nNav1.5 protein was expressed in plasma
membrane. Third, however, in ERalpha-positive cases, nNav1.5 protein expression
was observed in both plasma membrane and cytoplasm. In conclusion, nNav1.5
protein has a restricted expression pattern among human tissues. High level
expression occurs in BCa and associates with ERalpha status. These results
further support the proposition that nNav1.5 is a novel biomarker of metastatic
BCa.
PMID- 28698103
TI - Frameshift mutation and loss of expression of PLK2, a serine/threonine kinase
encoding gene, in colorectal cancers.
PMID- 28698104
TI - Pseudomonas aeruginosa quorum sensing modulates immune responses: An updated
review article.
AB - Pseudomonas aeruginosa is an opportunistic bacterium which induces some
complications in immunocompromised patients. Pseudomonas aeruginosa is a quorum
sensing using bacterium which regulates its genes expression. The bacterium uses
two famous pathways for quorum sensing entitled LasI/LasR and RhlI/RhlR systems.
It has been documented that the bacteria which use quorum sensing are able to
overcome immune responses. This review article aims to present recent information
regarding the effects of Pseudomonas aeruginosa quorum sensing systems on the
host immune responses.
PMID- 28698105
TI - Magnetic resonance imaging (MRI)-defined cartilage degeneration and joint pain
are associated with poor physical function in knee osteoarthritis - the Oulu Knee
Osteoarthritis study.
AB - OBJECTIVE: The main aim was to investigate the associations between Magnetic
Resonance Imaging (MRI)-defined structural pathologies of the knee and physical
function. DESIGN: A cohort study with frequency matching on age and sex with
eighty symptomatic subjects with knee pain and suspicion or diagnosis of knee
osteoarthritis (OA) and 57 asymptomatic subjects was conducted. The subjects
underwent knee MRI, and the severity of structural changes was graded by MRI
Osteoarthritis Knee Score (MOAKS) in separate knee locations. WOMAC function
subscores were recorded and physical function tests (20-m and 5-min walk, stair
ascending and descending, timed up & go and repeated sit-to-stand tests)
performed. The association between MRI-defined structural pathologies and
physical function tests and WOMAC function subscores were evaluated by linear
regression analysis with adjustment for demographic factors, other MRI-features
and pain with using effect size (ES) as a measure of the magnitude of an
association. RESULTS: Cartilage degeneration showed significant association with
poor physical performance in TUG-, stair ascending and descending-, 20-m- and 5
min walk-tests (ESs in the subjects with cartilage degeneration anywhere between
0.134 [95%CI 0.037-0.238] and 0.224 [0.013-0.335]) and with increased WOMAC
function subscore (ES in the subjects with cartilage degeneration anywhere 0.088
[0.012-0.103]). Also, lateral meniscus maceration and extrusion were associated
with poor performance in stair ascending test (ESs 0.067 [0.008-0.163] and 0.077
[0.012-0.177]). CONCLUSIONS: After adjustments cartilage degeneration was
associated with both decreased self-reported physical function and poor
performance in the physical function tests. Furthermore, subjects with lateral
meniscus maceration and extrusions showed significantly worse performance in
stair ascending tests.
PMID- 28698106
TI - Longitudinal change in thigh muscle strength prior to and concurrent with
symptomatic and radiographic knee osteoarthritis progression: data from the
Osteoarthritis Initiative.
AB - OBJECTIVE: To investigate whether symptomatic and/or radiographic knee
osteoarthritis (KOA) progression is associated with prior and/or concurrent
change in thigh muscle strength in men or women. DESIGN: Osteoarthritis
Initiative (OAI) participants with isometric muscle strength measurements at
baseline, 2- and 4-year follow-up (n = 1785: 1016 women) were grouped into 1)
those with vs without symptomatic progression (i.e., increase >=9 in WOMAC-pain
[scale: 0-100]); and 2) those with vs without radiographic progression (i.e.,
decrease in minimum joint space width (JSW) >=0.7 mm) between year-two and year
four follow-up. Sex-specific changes in thigh muscle strength concurrent (between
year-two and year-four follow-up) and prior to (between baseline and year-two
follow-up) symptomatic and radiographic progression were compared between groups
(progression vs no progression) using analysis of covariance, with adjustment for
age and body mass index. RESULTS: In women, but not in men, loss in knee extensor
and flexor strength was greater concurrent with symptomatic progression
(extensors: -3.7%, 95% confidence interval [CI] -6.4, -0.9; flexors: -7.2% 95% CI
-10.7, -3.7) than in women without symptomatic progression (extensors: -0.3%, 95%
CI -1.9, 1.3, P = 0.030; flexors: -2.6%, 95% CI -4.7, -0.6, P = 0.018). No
association was found between extensor or flexor strength loss concurrent to
radiographic progression, in either men or women, nor any statistically
significant association between prior change in muscle strength with symptomatic
or radiographic progression. CONCLUSION: These findings suggest that there is
concurrent but not prior longitudinal association between loss in muscle strength
and symptomatic KOA progression that is specific to women.
PMID- 28698107
TI - Dynamic graph metrics: Tutorial, toolbox, and tale.
AB - The central nervous system is composed of many individual units - from cells to
areas - that are connected with one another in a complex pattern of functional
interactions that supports perception, action, and cognition. One natural and
parsimonious representation of such a system is a graph in which nodes (units)
are connected by edges (interactions). While applicable across spatiotemporal
scales, species, and cohorts, the traditional graph approach is unable to address
the complexity of time-varying connectivity patterns that may be critically
important for an understanding of emotional and cognitive state, task-switching,
adaptation and development, or aging and disease progression. Here we survey a
set of tools from applied mathematics that offer measures to characterize dynamic
graphs. Along with this survey, we offer suggestions for visualization and a
publicly-available MATLAB toolbox to facilitate the application of these metrics
to existing or yet-to-be acquired neuroimaging data. We illustrate the toolbox by
applying it to a previously published data set of time-varying functional graphs,
but note that the tools can also be applied to time-varying structural graphs or
to other sorts of relational data entirely. Our aim is to provide the
neuroimaging community with a useful set of tools, and an intuition regarding how
to use them, for addressing emerging questions that hinge on accurate and
creative analyses of dynamic graphs.
PMID- 28698109
TI - Myelin structure in unfixed, single nerve fibers: Scanning X-ray microdiffraction
with a beam size of 200nm.
AB - Previous raster-scanning with a 1MUm X-ray beam of individual, myelinated fibers
from glutaraldehyde-fixed rat sciatic nerve revealed a spatially-dependent
variation in the diffraction patterns from single fibers. Analysis indicated
differences in the myelin periodicity, membrane separations, distribution of
proteins, and orientation of membrane lamellae. As chemical fixation is known to
produce structural artifacts, we sought to determine in the current study whether
the structural heterogeneity is intrinsic to unfixed myelin. Using a 200nm-beam
that was about five-fold smaller than before, we raster-scanned individual
myelinated fibers from both the peripheral (PNS; mouse and rat sciatic nerves)
and central (CNS; rat corpus callosum) nervous systems. As expected, the membrane
stacking in the internodal region was nearly parallel to the fiber axis and in
the paranodal region it was perpendicular to the axis. A myelin lattice was also
frequently observed when the incident beam was injected en face to the sheath.
Myelin periodicity and diffracted intensity varied with axial position along the
fiber, as did the calculated membrane profiles. Raster-scanning with an X-ray
beam at sub-micron resolution revealed for the first time that the individual
myelin sheaths in unfixed nerve are heterogeneous in both membrane structure and
packing.
PMID- 28698110
TI - Response to the letter to the editor by Berciano J & Garcia A.
PMID- 28698108
TI - Imaging at ultrahigh magnetic fields: History, challenges, and solutions.
AB - Following early efforts in applying nuclear magnetic resonance (NMR) spectroscopy
to study biological processes in intact systems, and particularly since the
introduction of 4 T human scanners circa 1990, rapid progress was made in imaging
and spectroscopy studies of humans at 4 T and animal models at 9.4 T, leading to
the introduction of 7 T and higher magnetic fields for human investigation at
about the turn of the century. Work conducted on these platforms has provided
numerous technological solutions to challenges posed at these ultrahigh fields,
and demonstrated the existence of significant advantages in signal-to-noise ratio
and biological information content. Primary difference from lower fields is the
deviation from the near field regime at the radiofrequencies (RF) corresponding
to hydrogen resonance conditions. At such ultrahigh fields, the RF is
characterized by attenuated traveling waves in the human body, which leads to
image non-uniformities for a given sample-coil configuration because of
destructive and constructive interferences. These non-uniformities were initially
considered detrimental to progress of imaging at high field strengths. However,
they are advantageous for parallel imaging in signal reception and transmission,
two critical technologies that account, to a large extend, for the success of
ultrahigh fields. With these technologies and improvements in instrumentation and
imaging methods, today ultrahigh fields have provided unprecedented gains in
imaging of brain function and anatomy, and started to make inroads into
investigation of the human torso and extremities. As extensive as they are, these
gains still constitute a prelude to what is to come given the increasingly larger
effort committed to ultrahigh field research and development of ever better
instrumentation and techniques.
PMID- 28698111
TI - Phylogeny and biogeography of Maclura (Moraceae) and the origin of an
anachronistic fruit.
AB - BACKGROUND AND AIMS: Maclura (ca. 12spp., Moraceae) is a widespread genus of
trees and woody climbers found on five continents. Maclura pomifera, the Osage
orange, is considered a classic example of an anachronistic fruit. Native to the
central USA, the grapefruit-sized Osage oranges are unpalatable and have no known
extant native dispersers, leading to speculation that the fruits were adapted to
extinct megafauna. Our aim was to reconstruct the phylogeny, estimate divergence
dates, and infer ancestral ranges of Maclura in order to test the monophyly of
subgeneric classifications and to understand evolution and dispersal patterns in
this globally distributed group. METHODS: Employing Bayesian and maximum
likelihood methods, we reconstructed the Maclura phylogeny using two nuclear and
five chloroplast loci from all Maclura species and outgroups representing all
Moraceae tribes. We reconstructed ancestral ranges and syncarp sizes using a
family level dated tree, and used Ornstein-Uhlenbeck models to test for
significant changes in syncarp size in the Osage orange lineage. KEY RESULTS: Our
analyses support a monophyletic Maclura with a Paleocene crown. Subgeneric
sections were monophyletic except for the geographically-disjunct Cardiogyne.
There was strong support for current species delineations except in the
widespread M. cochinchinensis. South America was reconstructed as the ancestral
range for Maclura with subsequent colonization of Africa and the northern
hemisphere. The clade containing M. pomifera likely diverged in the Oligocene,
closely coinciding with crown divergence dates of the mammoth/mastodon and sloth
clades that contain possible extinct dispersers. The best fitting model for
syncarp size evolution indicated an increase in both syncarp size and the rate of
syncarp size evolution in the Osage orange lineage. CONCLUSIONS: We conclude that
our findings are consistent with the hypothesis that M. pomifera was adapted to
dispersal by extinct megafauna. In addition, we consider dispersal rather than
vicariance to be most likely responsible for the present distribution of Maclura,
as crown divergence post-dated the separation of Africa and South America. We
propose revised sectional delimitations based on the phylogeny. This study
represents a complete phylogenetic and biogeographic analysis of this globally
distributed genus and provides a basis for future work, including a taxonomic
revision.
PMID- 28698112
TI - Slow aging in mammals-Lessons from African mole-rats and bats.
AB - Traditionally, the main mammalian models used in aging research have been mice
and rats, i.e. short-lived species that obviously lack effective maintenance
mechanisms to keep their soma in a functional state for prolonged periods of
time. It is doubtful that life-extending mechanisms identified only in such short
lived species adequately reflect the diversity of longevity pathways that have
naturally evolved in mammals, or that they have much relevance for long-lived
species such as humans. Therefore, some complementary, long-lived mammalian
models have been introduced to aging research in the past 15-20 years,
particularly naked mole-rats (and to a lesser extent also other mole-rats) and
bats. Here, I summarize and compare the most important results regarding various
aspects of aging - oxidative stress, molecular homeostasis and repair, and
endocrinology - that have been obtained from studies using these new mammalian
models of high longevity. I argue that the inclusion of these models was an
important step forward, because it drew researchers' attention to certain
oversimplifications of existing aging theories and to several features that
appear to be universal components of enhanced longevity in mammals. However, even
among mammals with high longevity, considerable variation exists with respect to
other candidate mechanisms that also must be taken into account if inadequate
generalizations are to be avoided.
PMID- 28698113
TI - Patient-specific biomechanical model of hypoplastic left heart to predict post
operative cardio-circulatory behaviour.
AB - Hypoplastic left heart syndrome is a complex congenital heart disease
characterised by the underdevelopment of the left ventricle normally treated with
a three-stage surgical repair. In this study, a multiscale closed-loop cardio
circulatory model is created to reproduce the pre-operative condition of a
patient suffering from such pathology and virtual surgery is performed. Firstly,
cardio-circulatory parameters are estimated using a fully closed-loop cardio
circulatory lumped parameter model. Secondly, a 3D standalone FEA model is build
up to obtain active and passive ventricular characteristics and unloaded
reference state. Lastly, the 3D model of the single ventricle is coupled to the
lumped parameter model of the circulation obtaining a multiscale closed-loop pre
operative model. Lacking any information on the fibre orientation, two cases were
simulated: (i) fibre distributed as in the physiological right ventricle and (ii)
fibre as in the physiological left ventricle. Once the pre-operative condition is
satisfactorily simulated for the two cases, virtual surgery is performed. The
post-operative results in the two cases highlighted similar hemodynamic behaviour
but different local mechanics. This finding suggests that the knowledge of the
patient-specific fibre arrangement is important to correctly estimate the single
ventricle's working condition and consequently can be valuable to support
clinical decision.
PMID- 28698114
TI - Response to Xuerong Luo et al., Letter to the Editor.
PMID- 28698115
TI - Interleukin 17 selectively predicts better outcomes with bupropion-SSRI
combination: Novel T cell biomarker for antidepressant medication selection.
AB - BACKGROUND: Interleukin 17 (IL-17) is produced by highly inflammatory Th17 cells
and has been implicated in pathophysiology of depression. IL-17 putatively
disrupts the blood brain barrier and affects dopamine synthesis whereas dopamine
has been shown to decrease Th17 cell-mediated immune response. Nevertheless,
whether IL-17 can predict differential treatment outcome with antidepressants
modulating dopaminergic transmission is unknown. METHODS: IL-17 and other T cell
and non-T cell markers (Th1, Th2 and non-T cell markers) were measured with the
Bioplex ProTM human cytokine 27-plex kit in the Combining Medications to Enhance
Depression Outcomes (CO-MED) trial participants who provided baseline plasma and
were treated with either bupropion plus escitalopram (bupropion-SSRI),
escitalopram plus placebo (SSRI monotherapy), or venlafaxine plus mirtazapine
(n=166). Differential changes in symptom severity and side-effects based on
levels of IL-17 and other T and non-T cell markers were tested using a treatment
arm-by-biomarker interaction in separate repeated measures mixed model analyses.
Subsequent analyses stratified by treatment arm were conducted for those markers
with a significant interaction. RESULTS: There was a significant treatment-arm-by
IL-17 interaction for depression severity (p=0.037) but not for side-effects
(p=0.28). Higher baseline IL-17 level was associated with greater reduction in
depression severity (effect size=0.78, p=0.008) in the bupropion-SSRI but not the
other two treatment arms. Other T and non-T cell markers were not associated with
differential treatment outcomes. CONCLUSION: Higher baseline levels of IL-17 are
selectively associated with greater symptomatic reduction in depressed patients
treated with bupropion-SSRI combination.
PMID- 28698117
TI - Letter to the Editor "Childhood maltreatment severity is associated with elevated
C-reactive protein and body mass index in adult with schizophrenia and bipolar
diagnoses".
PMID- 28698116
TI - Effects of early-life adversity on immune function are mediated by prenatal
environment: Role of prenatal alcohol exposure.
AB - The contribution of the early postnatal environment to the pervasive effects of
prenatal alcohol exposure (PAE) is poorly understood. Moreover, PAE often carries
increased risk of exposure to adversity/stress during early life. Dysregulation
of immune function may play a role in how pre- and/or postnatal adversity/stress
alters brain development. Here, we combine two animal models to examine whether
PAE differentially increases vulnerability to immune dysregulation in response to
early-life adversity. PAE and control litters were exposed to either limited
bedding (postnatal day [PN] 8-12) to model early-life adversity or normal
bedding, and maternal behavior and pup vocalizations were recorded. Peripheral
(serum) and central (amygdala) immune (cytokines and C-reactive protein - CRP)
responses of PAE animals to early-life adversity were evaluated at PN12.
Insufficient bedding increased negative maternal behavior in both groups. Early
life adversity increased vocalization in all animals; however, PAE pups vocalized
less than controls. Early-life adversity reduced serum TNF-alpha, KC/GRO, and IL
10 levels in control but not PAE animals. PAE increased serum CRP, and levels
were even higher in pups exposed to adversity. Finally, PAE reduced KC/GRO and
increased IL-10 levels in the amygdala. Our results indicate that PAE alters
immune system development and both behavioral and immune responses to early-life
adversity, which could have subsequent consequences for brain development and
later life health.
PMID- 28698118
TI - The efficacy of diagnostic imaging should guide oral and maxillofacial radiology
research.
PMID- 28698119
TI - Stress differentially affects the systemic and leukocyte estrogen network in
common carp.
AB - Both systemic and locally released steroid hormones, such as cortisol and
estrogens, show immunomodulatory actions. This research gives evidence that
circulating and leukocyte-derived estrogens can be involved in the regulation of
the immune response in common carp, during homeostasis and upon restraining
stress. It was found that stress reduced level of blood 17beta-estradiol (E2) and
down-regulated the gene expression of components of the "classical" estrogen
system: the nuclear estrogen receptors and the aromatase CYP19, in the
hypothalamus, the pituitary and in the ovaries. In contrast, higher gene
expression of the nuclear estrogen receptors and cyp19a was found in the head
kidney of stressed animals. Moreover, stress induced changes in the E2 level and
in the estrogen sensitivity at local/leukocyte level. For the first time in fish,
we showed the presence of physiologically relevant amounts of E2 and the
substrates for its conversion (estrone - E1 and testosterone - T) in head kidney
monocytes/macrophages and found that its production is modulated upon stress.
Moreover, stress reduced the sensitivity of leukocytes towards estrogens, by down
regulation the expression of the erb and cyp19 genes in carp phagocytes. In
contrast, era expression was up-regulated in the head kidney
monocytes/macrophages and in PBLs derived from stressed animals. We hypothesize
that, the increased expression of ERalpha, that was observed during stress, can
be important for the regulation of leukocyte differentiation, maturation and
migration. In conclusion, these results indicate that, in fish, the estrogen
network can be actively involved in the regulation of the systemic and local
stress response and the immune response.
PMID- 28698120
TI - Effectiveness of formalin-killed vaccines containing CpG oligodeoxynucleotide
1668 adjuvants against Vibrio harveyi in orange-spotted grouper.
AB - Vibrio harveyi is a major bacterial pathogen that causes serious vibriosis in
cultured groupers, leading to massive deaths. In this study, we evaluated the
immune responses and protective efficacy of vaccines containing V. harveyi
formalin-killed cells (FKC) formulated with CpG ODN 1668-enriched plasmids
(p30CpG and p60CpG) in the orange-spotted grouper. Results indicated that
antibody titres were remarkably increased in vaccinated fish 2 weeks post
immunisation. Expression level of major histocompatibility complex (MHC) class
II, CD 8, and toll-like receptor 9 was significantly upregulated in the spleen of
fish immunised with CpG ODN 1668-adjuvanted vaccines, as recorded at 6 weeks
after immunisation. Additionally, the FKC + p60CpG-vaccinated fish displayed
greater mRNA levels of MHC I and tumor necrosis factor-alpha. Of note, the
relative percent survival after V. harveyi challenge was significantly higher in
FKC + p60CpG-vaccinated fish (96.2%) than in FKC + p30CpG-vaccinated (79.8%) and
FKC-vaccinated fish (59.9%). These results demonstrate that the FKC + CpG ODN
1668 vaccines are promising candidates that could enhance both innate and
adaptive immune responses, conferred remarkable protection, and CpG ODN 1668 is a
potential adjuvant for vaccines against V. harveyi.
PMID- 28698121
TI - The transcriptional response of the Pacific oyster Crassostrea gigas against
acute heat stress.
AB - The Pacific oyster, Crassostrea gigas, has evolved sophisticated mechanisms to
adapt the changing ambient conditions, and protect themselves from stress-induced
injuries. In the present study, the expression profiles of mRNA transcripts in
the haemocytes of oysters under heat stress were examined to reveal the possible
mechanism of heat stress response. There were 23,315, 23,904, 23,123 and 23,672
transcripts identified in the haemocytes of oysters cultured at 25 degrees C for
0, 6, 12, and 24 h (designed as B, H6, H12, H24), respectively. And 22,330
differentially expressed transcripts (DTs) were yielded in the pairwise
comparisons between the above four samples, which corresponded to 8074 genes.
There were 9, 12 and 22 Gene Ontology (GO) terms identified in the DT pairwise
comparison groups of H6_B, H12_H6 and H24_H12, respectively, and the richest GO
terms in biological process category were cellular catabolic process,
translational initiation and apoptotic process, respectively. There were 108, 102
and 102 KEGG pathways successfully retrieved from DTs comparison groups DTH6_B,
DTH12_H6 and DTH24_H12, respectively, among which 93 pathways were shared by all
three comparison groups, and most of them were related to metabolism of protein,
carbohydrate and fat. The expression patterns of 12 representative heat stress
response-relevant genes detected by quantitative real-time PCR (qRT-PCR) were
similar to those obtained from transcriptome analysis. By flow cytometric
analysis, the apoptosis rate of haemocytes increased significantly after oysters
were treated at 25 degrees C for 24 h and recovered at 4 degrees C for 12 h (p
< 0.05) and 36 h (p < 0.01), and it also increased significantly when the heat
treatment lasted to 60 h (p < 0.01). The present results indicated that, when
oysters encountered short term heat stress, the expression of genes related to
energy metabolism, as well as unfolded protein response (UPR) and anti-apoptotic
system, were firstly regulated to maintain basic life activities, and then a
large number of genes involved in stabilizing protein conformation and
facilitating further protein refolding were activated to repair the stress
injury. However, the stress injury gradually became irreparable with the stress
persisting, and apoptosis was activated when the heat treatment prolonged to 24
h. The information was useful to better understand the molecular mechanism of
heat stress response and develop strategies for the improvement of oyster
survival rate during summer high-temperature period.
PMID- 28698122
TI - Transcriptome analysis and discovery of genes involved in immune pathways in
large yellow croaker (Larimichthys crocea) under high stocking density stress.
AB - The large yellow croaker, Larimichthys crocea, is an economically important
maricultured species in southeast China. Owing to the importance of stocking
densities in commercial fish production, it is crucial to establish the
physiological responses and molecular mechanisms that govern adaptation to
crowding in order to optimize welfare and health. In the present study, an
extensive immunity-related analysis was performed at the transcriptome level in
L. crocea in response to crowding stress. Over 145 million high-quality reads
were generated and de novo assembled into a final set of 40,123 unigenes. Gene
Ontology and genome analyses revealed that molecular function, biological
process, intracellular, ion binding, and cell process were the most highly
enriched pathways among genes that were differentially expressed under stress.
Among all of the pathways involved, 16 pathways were related to the immune
system, among which the complement and coagulation cascades pathway was the most
enriched for differentially expressed immunity-related genes, followed by the
chemokine signaling pathway, toll-like receptor signaling pathway, and leukocyte
transendothelial migration pathway. The consistently high expression of immune
related genes in the complement and coagulation cascades pathway (from 24 to 96 h
after being subjected to stress) suggested its importance in both response to
stress and resistance against bacterial invasion at an early stage. These results
also demonstrated that crowding can significantly induce immunological responses
in fish. However, long-term exposure to stress eventually impairs the defense
capability in fish.
PMID- 28698123
TI - Identification, molecular evolution of toll-like receptors in a Tibetan
schizothoracine fish (Gymnocypris eckloni) and their expression profiles in
response to acute hypoxia.
AB - Hypoxia plays an important role in regulating a variety of physiological
responses as well as in pathological situations, but to date the roles of Toll
like receptors (TLRs) in fish in response to hypoxia are still poorly understood.
Here, we sequenced the transcriptome of G. eckloni and identified the members of
TLR family by scanning transcriptome, and then investigated the expression
profiles of a complete set of TLRs in G. eckloni in response to acute hypoxia (4
h at DO = 0.3 +/- 0.1 mg/L). The de novo-assembled transcriptome consisted of a
total of 162,235 transcripts, further clustered into 110,231 unigenes. Based on
the transcriptome, a total of 18 TLRs were identified in G. eckloni, and of them
three TLRs (TLR5, TLR8 and TLR22) possessed two distinct paralogous genes. The
duplicated genes of TLR22 were discovered for the first time in cyprinid fish,
but did not origin from a recent duplication event. Of them TLR22b may be
specific for schizothoracine fish, at least for G. eckloni. Phylogenetic analysis
supported the classification of TLRs into six families as in other vertebrates
but was partly different from the previous study. The sliding window analysis
showed strong signals of positive selection in TLR2, TLR 4, TLR 5a, TLR 7, TLR
19, TLR 20, TLR 21, TLR 22a and TLR 22b, but most codons under positive selection
were located in the putative LRR regions. The mRNA expression of most TLRs in
head kidney, spleen and gill decreased significantly or remained unchanged under
acute hypoxia, whereas acute hypoxia increased expressions of TLR2 and TLR3 in
head kidney, of TLR8a, TLR12 and TLR19 in spleen, and of TLR1 in gill, suggesting
tissues-specific expressions of TLRs play important roles in mediating innate
immune responses for host defense against tissue damages or physiological changes
induced by hypoxia.
PMID- 28698124
TI - The role of phosphatidylinositol-3-OH-kinase (PI3-kinase) and respiratory burst
enzymes in the [omim][BF4]-mediated toxic mode of action in mussel hemocytes.
AB - The present study investigates the role of phosphatidylinositol-3-OH-kinase (PI3
kinase) and respiratory burst enzymes, NADPH oxidase and NO synthase, in the 1
methyl-3-octylimidazolium tetrafluoroborate ([omim][BF4])-mediated toxic mode of
action in mussel hemocytes. Specifically, cell viability (using the neutral red
uptake assay) was primarily tested in hemocytes treated with different
concentrations of [omim][BF4] (0.1-10 mg L-1) and thereafter [omim][BF4]-mediated
oxidative (in terms of superoxide anions/O2- and nitric oxide/NO generation, as
well as the enhancement of lipid peroxidation by-products, in terms of
malondialdehyde/MDA) and genotoxic (in terms of DNA damage) effects were
determined in hemocytes treated with 1 mg L-1 [omim][BF4]. Moreover, in order to
investigate, even indirectly and non-entirely specific, the role of PI3-kinase,
NADPH oxidase and NO synthase, the [omim][BF4]-mediated effects were also
investigated in hemocytes pre-incubated with wortmannin (50 nM),
diphenyleneiodonium chloride (DPI 10 MUM) and NG-nitro-l-arginine methyl ester (l
NAME 10 MUM), respectively. The results showed that [omim][BF4] ability to
enhance O2-, NO, MDA and DNA damage, via its interaction with cellular membranes,
was significantly attenuated in the presence of each inhibitor in almost all
cases. The current findings revealed for the first time that certain signaling
molecules, such as PI3-kinase, as well as respiratory burst enzymes activation,
such as NADPH oxidase and NO synthase, could merely attribute to the [omim][BF4]
mediated mode of action, thus enriching our knowledge for the molecular
mechanisms of ILs toxicity.
PMID- 28698125
TI - Effects of Lactobacillus delbrueckii on immune response, disease resistance
against Aeromonas hydrophila, antioxidant capability and growth performance of
Cyprinus carpio Huanghe var.
AB - The aim of the present study was to investigate effects of dietary Lactobacillus
delbrueckii (L. delbrueckii) on immune response, disease resistance against
Aeromonas hydrophila (A. hydrophila), antioxidant capability and growth
performance of Cyprinus carpio Huanghe var. 450 fish (mean weight of 1.05 +/-
0.03 g) were randomly distributed into five groups that fed diets containing
different levels of L. delbrueckii (0, 1 * 105, 1 * 106, 1 * 107 and 1 * 108 CFU
g-1) for 8 weeks. The results showed that intestinal immune parameters such as
lysozyme, acid phosphatase, and myeloperoxidase activities, immunoglobulin M
content, and the survival rate were improved in fish fed with 1 * 106 and 1 * 107
CFU g-1L. delbrueckii. In addition, 1 * 107 CFU g-1L. delbrueckii supplementation
down-regulated mRNA levels of TNF-alpha, IL-8, IL-1beta and NF-kappaBp65, and up
regulated IL-10 and TGF-beta mRNA levels in the intestine. The survival rate was
significantly (P < 0.05) higher (68.33%) in fish fed 1 * 106 CFU g-1L.
delbrueckii than the control diet-fed group (40%) after challenge by A.
hydrophila. Fish fed with diet containing 1 * 106 CFU g-1L. delbrueckii showed
higher antioxidant enzyme activities such as superoxide dismutase (SOD), catalase
(CAT), glutathione peroxidase (GPX), and total antioxidant capacity (T-AOC) and
lower MDA concentrations than those of the control group (P < 0.05). The relative
gene expression (SOD, CAT, GPX) showed the same trend with their activities. In
addition, the growth performance was significantly improved in fish fed with the
diet containing 1 * 106 and 1 * 107 CFU g-1L. delbrueckii (P < 0.05). These
results demonstrated that dietary optimal levels of L. delbrueckii enhanced
immunity, disease resistance against A. hydrophila antioxidant capability and
growth performance in Cyprinus carpio Huanghe var.
PMID- 28698126
TI - Molecular characterization and expression analyses of toll like receptor-5
induced by Vibrio parahaemolyticus antigens in Pacific red snapper.
AB - Toll-like receptor 5 (TLR5) is a member of TLRs family responsible for the
bacterial flagellin recognition in vertebrates. Herein, the TLR5M gene structure
of Pacific red snapper (Lutjanus peru) was characterized. The full-length cDNA of
LpTLR5M comprises an open reading frame (ORF) of 2715 bp, encoding a polypeptide
of 904 amino acids including 9 LRRs (residues 119-562) and one LRR-CT domain
(residues 593-646) at the extracellular region, and a TIR domain (residues 710
904) in the cytoplasmic region. The amino acid sequence in L. peru TLR5 showed
high identity (66-69%) with TLR5 from Paralichthys olivaceus and Scophthalmus
maximus. Quantitative real-time PCR (qPCR) analysis demonstrated the constitutive
expression of LpTLR5M mRNA in all the examined tissues, with higher levels in
intestine, liver, and head-kidney. Furthermore, expression of LpTLR5M and five
cytokine genes was also investigated 24 h and one week post-stimulation in fish
intraperitoneally injected with ToxA, live V. parahaemolyticus (Vp) or V.
parahaemolyticus Lysate antigens. TLR5M was significantly induced in fish
infected with Vp. The pro-inflammatory cytokines IL-6, IL8 and IL-12 were
significantly up-regulated in head-kidney in fish stimulated with Vp, while in
intestine upregulation was observed following ToxA or Lysate injection. In
contrast, IL-17 mRNA was significantly up-regulated in the intestine from fish
infected with live Vp at 24 h post-injection. The results indicate that Lysate
and Vp antigens can induce an immune response via TLR5M and that cytokines have
an important role in the defense mechanisms against V. parahaemolyticus.
PMID- 28698127
TI - Dietary protein levels regulated antibacterial activity, inflammatory response
and structural integrity in the head kidney, spleen and skin of grass carp
(Ctenopharyngodon idella) after challenged with Aeromonas hydrophila.
AB - This study investigated the effects of dietary protein levels on disease
resistance, immune function and structural integrity in the head kidney, spleen
and skin of grass carp (Ctenopharyngodon idella). A total of 540 grass carp
(264.11 +/- 0.76 g) were fed six diets containing graded levels of protein
(143.1, 176.7, 217.2, 257.5, 292.2 and 322.8 g digestible protein kg-1 diet) for
8 weeks. After the growth trial, fish were challenged with Aeromonas hydrophila
for 14 days. The results indicated that optimal levels of dietary protein: (1)
(1) increased the lysozyme (LA) and acid phosphatase (ACP) activities and the
complement 3 (C3) and C4 contents, up-regulated antimicrobial peptides, anti
inflammatory cytokines, inhibitor of kappaBalpha, target of rapamycin and
ribosomal protein S6 kinases 1 mRNA levels, whereas down-regulated pro
inflammatory cytokines, nuclear factor kappa B (NF-kappaB) P65, IKKbeta,
IKKgamma, eIF4E-binding proteins (4E-BP) 1 and 4E-BP2 mRNA levels in the head
kidney, spleen and skin of grass carp (P < 0.05), suggesting that optimal level
of dietary protein could enhance immune function in the head kidney, spleen and
skin of fish; (2) increased the activities and mRNA levels of antioxidant
enzymes, enhanced the glutathione content, decreased reactive oxygen species,
malondialdehyde (MDA) and protein carbonyl contents, and up-regulated the mRNA
levels of NF-E2-related factor 2, B-cell lymphoma protein-2, inhibitor of
apoptosis proteins, myeloid cell leukemia-1 and tight junction complexes, whereas
down-regulated Kelch-like-ECH-associated protein (Keap) 1b, cysteinyl aspartic
acid-protease 3, 8, 9, Fas ligand, apoptotic protease activating factor-1, Bcl-2
associated X protein and myosin light chain kinase mRNA levels in the head
kidney, spleen and skin of grass carp (P < 0.05), indicating that optimal level
of dietary protein could improve structural integrity in the head kidney, spleen
and skin of fish. Finally, based on the skin hemorrhage and lesion morbidity, LA
activity and MDA content, the optimal levels of dietary protein for grass carp
(264 g-787 g) were estimated to be 241.45 g kg-1 diet (217.68 g digestible
protein kg-1 diet), 301.68 g kg-1 diet (265.48 g digestible protein kg-1 diet)
and 307.84 g kg-1 diet (272.71 g digestible protein kg-1 diet), respectively.
PMID- 28698128
TI - Genome-wide identification, characterization and expression analyses of TLRs in
Yesso scallop (Patinopecten yessoensis) provide insight into the disparity of
responses to acidifying exposure in bivalves.
AB - Toll-like receptors (TLRs) play a crucial role in innate immunity by recognizing
specific pathogen-associated molecular patterns, including lipoproteins,
lipopeptides, lipopolysaccharide, flagellin, dsRNA, ssRNA and CpG DNA motifs.
Although significant effects of TLRs on immunity have been reported in most
vertebrates and some invertebrates, the complete TLR superfamily has not been
systematically characterized in scallops. In this study, 18 TLR genes were
identified from Yesso scallop (Patinopecten yessoensis) using whole-genome
scanning. Phylogenetic and protein structural analyses were performed to
determine the identities and evolutionary relationships of the 18 genes.
Extensive expansion of TLR genes from the Yesso scallop genome indicated gene
duplication events. In addition, expression profiling of PyTLRs was performed at
different acidifying exposure levels (pH = 6.50, 7.50) with different challenge
durations (3, 6, 12 and 24 h) via in silico analysis using transcriptome and
genome databases. Our results confirmed the inducible expression patterns of
PyTLRs under acidifying exposure, and the responses to immune stress may have
arisen through adaptive recruitment of tandem duplications of TLR genes.
Collectively, this study provides novel insight into PyTLRs as well as the
specific role and response of TLR signaling pathways in host immune responses
against acidifying exposure in bivalves.
PMID- 28698129
TI - An efficient agro-industrial complex in Almeria (Spain): Towards an integrated
and sustainable bioeconomy model.
AB - In the last ten years, bioeconomy strategies and policy-related bioeconomy
initiatives have been developed all over the world. Some of them are currently in
the process of translation into specific actions. In most cases, the approaches
followed have been top-down policy-related initiatives, triggered by the public
sector originating a dynamic which can bring together different bioeconomy
stakeholders i.e. industry, academia, financial operators and farmers. This
article describes a bottom-up situation with unique bioeconomy-related features
that deserve specific attention. Over the last 40 years, Almeria, in the south
east of Spain, has developed one of the most efficient agro-industrial complexes
in the world, evolving from a traditional and subsistence agriculture, to
becoming the major vegetable exporter in the European Union (EU). This growth set
aside issues such as sustainability, long-term perspectives on water resources or
agricultural waste. However, societal concerns about a circular economy, as well
as policy initiatives in the EU and in Spain on bioeconomy are changing the
situation towards an integrated, efficient and sustainable bioeconomy system.
Currently, the production chain demands innovations related to the use of biomass
as source of bioproducts and bioenergy in order to remain competitive. Some
positive aspects are the relatively small size of the agro-industrial area,
making transport and communications rapid and easy, and the existence of strong
and dedicated academic and financial institutions. This article outlines the
current efforts and initiatives to couple the existing successful agro-industrial
complex with that of a fully sustainable bioeconomy model.
PMID- 28698130
TI - Enzymatic hydrolysis of poly(ethyleneterephthalate) used for and analysed by pore
modification of track-etched membranes.
AB - The potential of limited enzymatic poly(ethylene terephthalate) (PET) surface
hydrolysis for the modification of track-etched (TE) membranes was investigated.
Cutinases 1 and 2 from Thermobifida cellulosilytica as well as a fusion protein
of cutinase 1 with the polymer binding module from the polyhydroxyalkanoate
depolymerase of Alcaligenes faecalis (Thc_Cut1_PBM) were shown to hydrolyse
highly crystalline PET TE membranes with a pore diameter of ~120nm at very narrow
size distribution. Furthermore the effects of surface chemistry were investigated
by comparison of enzymatic hydrolysis by Thc_Cut1_PBM of "as received" PET TE
membranes with two surface functionalized versions towards a "hydrophilic" and a
more "hydrophobic" surface. The effects of adsorbed protein and the efficacy of
cleaning steps after enzymatic treatment were elucidated by complementary methods
for surface analysis and membrane characterization. With the optimized cleaning
protocol, all adsorbed protein could be removed from the enzyme-treated membranes
and effects of chemical surface functionalization of the PET TE membranes were
demonstrated. The highest efficiency of enzymatic surface hydrolysis was observed
for the original PET TE membranes, leading to an 0.36% weight loss corresponding
to a removal of ~3nm PET from the entire surface of the porous membrane. This
correlates very well with the measured increase of barrier pore diameter by 4nm
(a radius reduction? of 2nm), leading to about a two-fold increased water
permeability.
PMID- 28698131
TI - White grape pomace extracts, obtained by a sequential enzymatic plus ethanol
based extraction, exert antioxidant, anti-tyrosinase and anti-inflammatory
activities.
AB - The present work aimed at optimizing a two-step enzymatic plus solvent-based
process for the recovery of bioactive compounds from white grape (Vitis vinifera
L., mix of Trebbiano and Verdicchio cultivars) pomace, the winemaking primary by
product. Phenolic compounds solubilised by water enzyme-assisted and ethanol
based extractions of wet (WP) and dried (DP) pomace were characterised for
composition and tested for antioxidant, anti-tyrosinase and anti-inflammatory
bioactivities. Ethanol treatment led to higher phenol yields than water
extraction, while DP samples showed the highest capacity of releasing
polyphenols, most probably as a positive consequence of the pomace drying
process. Different compositions and bioactivities were observed between water and
ethanol extracts and among different treatments and for the first time the anti
tyrosinase activity of V. vinifera pomace extracts, was here reported. Enzymatic
treatments did not significantly improve the total amount of solubilised
compounds; Celluclast in DP led to the recovery of extracts enriched in specific
compounds, when compared to control. The best extracts (enzymatic plus ethanol
treatment total levels) were obtained from DP showing significantly higher
amounts of polyphenols, flavonoids, flavanols and tannins and exerted higher
antioxidant and anti-tyrosinase activities than WP total extracts. Conversely,
anti-inflammatory capacity was only detected in water (with and without enzyme)
extracts, with WP samples showing on average a higher activity than DP. The
present findings demonstrate that white grape pomace constitute a sustainable
source for the extraction of phytochemicals that might be exploited as functional
ingredients in the food, nutraceutical, pharmaceutical or cosmetic industries.
PMID- 28698132
TI - The impact of emergency department crowding on outcomes, other aspects should not
be ignored.
PMID- 28698133
TI - Randomized controlled trial of internal and external targeted temperature
management methods in post- cardiac arrest patients.
AB - BACKGROUND: Targeted temperature management post-cardiac arrest is currently
implemented using various methods, broadly categorized as internal and external.
This study aimed to evaluate survival-to-hospital discharge and neurological
outcomes (Glasgow-Pittsburgh Score) of post-cardiac arrest patients undergoing
internal cooling verses external cooling. METHODOLOGY: A randomized controlled
trial of post-resuscitation cardiac arrest patients was conducted from October
2008-September 2014. Patients were randomized to either internal or external
cooling methods. Historical controls were selected matched by age and gender.
Analysis using SPSS version 21.0 presented descriptive statistics and frequencies
while univariate logistic regression was done using R 3.1.3. RESULTS: 23 patients
were randomized to internal cooling and 22 patients to external cooling and 42
matched controls were selected. No significant difference was seen between
internal and external cooling in terms of survival, neurological outcomes and
complications. However in the internal cooling arm, there was lower risk of
developing overcooling (p=0.01) and rebound hyperthermia (p=0.02). Compared to
normothermia, internal cooling had higher survival (OR=3.36, 95% CI=(1.130,
10.412), and lower risk of developing cardiac arrhythmias (OR=0.18, 95% CI=(0.04,
0.63)). Subgroup analysis showed those with cardiac cause of arrest (OR=4.29, 95%
CI=(1.26, 15.80)) and sustained ROSC (OR=5.50, 95% CI=(1.64, 20.39)) had better
survival with internal cooling compared to normothermia. Cooling curves showed
tighter temperature control for internal compared to external cooling.
CONCLUSION: Internal cooling showed tighter temperature control compared to
external cooling. Internal cooling can potentially provide better survival-to
hospital discharge outcomes and reduce cardiac arrhythmia complications in
carefully selected patients as compared to normothermia.
PMID- 28698134
TI - Effects of advanced life support on patients who suffered cardiac arrest outside
of hospital and were defibrillated.
AB - BACKGROUND: The effects and relative benefits of advanced airway management and
epinephrine on patients with out-of-hospital cardiac arrest (OHCA) who were
defibrillated are not well understood. METHODS: This was a prospective
observational study. Using data of all out-of-hospital cardiac arrest cases
occurring between 2005 and 2013 in Japan, hierarchical logistic regression and
conditional logistic regression along with time-dependent propensity matching
were performed. Outcome measures were survival and minimal neurological
impairment [cerebral performance category (CPC) 1 or 2] at 1month after the
event. RESULTS: We analyzed 37,873 cases that met the inclusion criteria. Among
propensity-matched patients, advanced airway management and/or prehospital
epinephrine use was related to decreased rates of 1-month survival (adjusted odds
ratio 0.88, 95% confidence interval 0.80 to 0.97) and CPC (1, 2) (adjusted odds
ratio 0.56, 95% confidence interval 0.48 to 0.66). Advanced airway management was
related to decreased rates of 1-month survival (adjusted odds ratio 0.89, 95%
confidence interval 0.81to 0.98) and CPC (1, 2) (adjusted odds ratio 0.54, 95%
confidence interval 0.46 to 0.64) in patients who did not receive epinephrine,
whereas epinephrine use was not related to the outcome measures. CONCLUSIONS: In
defibrillated patients with OHCA, advanced airway management and/or epinephrine
are related to reduced long-term survival, and advanced airway management is less
beneficial than epinephrine. However, the proportion of patients with OHCA who
responded to an initial shock was very low in the study subjects, and the
external validity of our findings might be limited.
PMID- 28698135
TI - MREG suppresses thyroid cancer cell invasion and proliferation by inhibiting Akt
mTOR signaling.
AB - Thyroid cancer has long been considered to arise in middle age and progress to
more aggressive and lethal cancers after its repeated proliferation. In this
research, we aimed at investigating the biological function and the underlying
molecular mechanism of Melanoregulin (MREG) in thyroid cancer. It was found that
the expression of MREG was significantly downregulated in thyroid cancer tissues.
The downregulation of MREG expression was caused by epigenetic methylation. MREG
overexpression could suppress the invasion and proliferation of thyroid cancer
cells. While MREG knockdown promoted the invasion and proliferation of thyroid
cancer cells. Furthermore, the phosphorylation of Akt or mTOR was decreased by
MREG overexpression and increased by MREG knockdown. Moreover, Dactolisib (the
inhibitor of mTOR) could abrogate silenced MREG induced thyroid cancer cell
invasion and proliferation. Taken together, MREG regulates thyroid cancer cell
invasion and proliferation through PI3K/Akt-mTOR signaling pathway. MREG may
serve as a promising therapeutic strategy for thyroid cancer.
PMID- 28698136
TI - Dynamic G protein alpha signaling in Arabidopsis innate immunity.
AB - Heterotrimeric G proteins composed of Galpha, Gbeta and Ggamma subunits are
evolutionarily conserved signaling modules involved in diverse biological
processes in plants and animals. The role and action of Galpha remain largely
enigmatic in plant innate immunity. We have recently demonstrated that
Arabidopsis Galpha (GPA1) is a key component of a new immune signaling pathway
activated by bacteria-secreted proteases. Here we show that GPA1 is also involved
in the signaling network of Arabidopsis in response to the bacterial flagellin
epitope flg22. Specifically, GPA1 plays a pivotal role in an immune pathway
involving the flg22 receptor FLS2, co-receptor BAK1, Regulator of G Signaling 1
(RGS1), and Arabidopsis Gbeta (AGB1), in which flg22 elicits GPA1/AGB1
dissociation from the FLS2/BAK1/RGS1 receptor complex. Consequently, we observed
flg22-induced degradation of FLS2, BAK1 and RGS1 but not GPA1 or AGB1. We also
found that GPA1 constitutively interacts with the NADPH oxidase RbohD to
potentiate flg22-induced ROS burst independently of the central cytoplasmic
kinase BIK1. Taken together, our work sheds multiple novel insights into the
functions and regulatory mechanisms of GPA1 in Arabidopsis innate immunity.
PMID- 28698137
TI - SSeCKS/AKAP12 induces repulsion between human prostate cancer and microvessel
endothelial cells through the activation of Semaphorin 3F.
AB - Metastasis remains the primary cause of prostate cancer related death. Cancer
cells need to contact endothelial cells and disrupt endothelial junctions to
cross the endothelium for invasion and metastasis. The suppression of heterotypic
repulsion between cancer and endothelial cells allows cancer cells to invade into
the surrounding tissue. Here, we demonstrate that SSeCKS/AKAP12 induced repulsion
between human prostate cancer and microvessel endothelial cells, which was
mediated by an angiogenesis inhibitor Semaphorin 3F. Moreover, we examined AKAP12
and Semaphorin 3F mRNA expression in 42 prostate cancer and 30 benign prostatic
hyperplasia tissue samples, and found that the expression of AKAP12 and
Semaphorin 3F mRNA was inversely associated with the degree of aggressiveness of
prostate cancer cells and tissues. An ordinal logistic regression analysis
indicates that there is a positive association between the expression of AKAP12
and Semaphorin 3F in prostate cancer, suggesting that the activation of
Semaphorin 3F by SSeCKS/AKAP12 may be involved in prostate cancer progression and
metastasis.
PMID- 28698138
TI - A novel fluorinated thiosemicarbazone derivative- 2-(3,4-difluorobenzylidene)
hydrazinecarbothioamide induces apoptosis in human A549 lung cancer cells via ROS
mediated mitochondria-dependent pathway.
AB - Thiosemicarbazone, a class of compounds with excellent biological activity,
especially antitumor activity, have attracted wide attention. In this study, a
novel fluorinated thiosemicarbazone derivative, 2-(3,4-difluorobenzylidene)
hydrazinecarbothioamide (compound 1) was synthesized and its antitumor activities
were further investigated on a non-small cell lung cancer cell line (A549) along
with its underlying mechanisms. Compound 1 showed significant anti-proliferative
activity on A549 cells, which was further proved by colony formation experiment.
Compound 1 also inhibits the invasion of A549 cells in a trans-well culture
system. Moreover, compound 1 markedly induced apoptosis on A549 cells, and the
ratio of Bcl-2/Bax was decreased while the amount of p53, Cleaved-Caspase 3 and
Cleaved-PARP expression were increased significantly. Compound 1 decreased the
mitochondrial membrane potential, while the content of reactive oxygen was
increased obviously. It is revealed that compound 1 mediated cell cycle arrest in
G0/G1 phase by reducing G1 phase dependent proteins, CDK4 and Cyclin D1. As a
result, it is indicated that compound 1 induced apoptosis on A549 cells was
realized by regulating ROS-mediated mitochondria-dependent signaling pathway.
PMID- 28698139
TI - 11beta-hydroxysteroid dehydrogenases-2 decreases the apoptosis of MC3T3/MLO-Y4
cells induced by glucocorticoids.
AB - The aim of the present study was to confirm the role of 11beta-hydroxysteroid
dehydrogenases type 2(11beta-HSD-2) in steroid induced osteonecrosis of the
femoral head(SANFH). We cultured mouse bone-like cells (MLO-Y4) and mouse
osteoblast-like cells (MC3T3-E1). After overexpressed 11beta-HSD-2 successfully,
we induced cell apoptosis by dexamethasone (DXM). The level of cell apoptosis,
the expression of Bcl-2 in MLO-Y4 cells and the expression of Fas and caspase8 in
MC3T3-E1 cells were detected. Then, we constructed 11beta-HSD-2 siRNA plasmid and
represented it on MLO-Y4/MC3T3-E1 Cells, to down-regulate the 11beta-HSD-2
expression. After that, we used dexamethasone to induce cell apoptosis. The level
of cell apoptosis, the expression of Bcl-2 in MLO-Y4 cells and the expression of
Fas and caspase8 in MC3T3-E1 cells were detected again. In the overexpression
model of cells, we found that the amount of cell apoptosis, the expression of Fas
and caspase8 in MC3T3-E1 cells are lower than that of control groups. The amount
of cell apoptosis, the expression of Fas and caspase8 in MC3T3-E1 cells were more
than before when we reduced the expression of 11beta-HSD-2. In our study, we
concluded that 11beta-HSD-2 plays an important role in the development of bone or
osteoblast cell apoptosis, and the decreased expression of 11beta-HSD-2 may
aggravate steroid induced bone/osteoblast cell apoptosis.
PMID- 28698140
TI - N-arachidonoyl glycine, another endogenous agonist of GPR55.
AB - Interest in lipoamino acids as endogenous modulators of G-protein coupled
receptors has escalated due to their involvement in a variety of physiologic
processes. In particular, a role for these amino acid conjugates has emerged in
the endocannabinoid system. The study presented herein investigated the effects
of N-arachidonoyl glycine (NAGly) on a candidate endocannabinoid receptor, GPR55.
Our novel findings reveal that NAGly induces concentration dependent increases in
calcium mobilization and mitogen-activated protein kinase activities in
HAGPR55/CHO cells. These increases were attenuated by the selective GPR55
antagonist ML193 (N-[4-[[(3,4-Dimethyl-5-isoxazolyl)amino]sulfonyl]phenyl]-6,8
dimethyl-2-(2-pyridinyl)-4-quinolinecarboxamide), supporting receptor mediated
signaling. To our knowledge this is the first report identifying GPR55 as a
target of the endogenous lipoamino acid, NAGly.
PMID- 28698141
TI - Epigenetic silencing of the Wnt antagonist APCDD1 by promoter DNA hyper
methylation contributes to osteosarcoma cell invasion and metastasis.
AB - Osteosarcoma (OS) is the most common type of bone tumor in children and adults.
However, the molecular mechanism underlying OS tumorigenesis remains unclear.
Here, we report that the expression of APCDD1, a Wnt antagonist, was reduced in
OS tissues and cells compared to adjacent normal tissue and osteoblast cells,
respectively. Mechanistically, this was due to increased levels of methylation in
the promoter region of the APCDD1 gene. Consistently, the DNA methyltransferase
inhibitor 5-AZA-dC, reduced DNA methylation in the APCDD1 promoter, and restored
APCDD1 expression in OS tissue and cells. Moreover, DNMT3a, but not DNMT1 or
DNMT3b, was the major DNA methyltransferase that facilitated hyper-methylation of
DNA in the APCDD1 promoter, thus reducing APCDD1 mRNA levels in OS tissues.
Importantly, ectopic expression of APCDD1 suppressed activity of the Wnt/beta
Catenin signaling pathway in OS cells and inhibited their invasion and reversed
their EMT-like properties, while depletion of APCDD1 promoted invasion and
metastasis of osteosarcoma cells in vitro and in vivo. Thus, we have provided the
first evidence that APCDD1 expression is epigenetically silenced in OS, which may
facilitate invasion and metastasis of OS cells.
PMID- 28698142
TI - A novel oncolytic adenovirus targeting Wnt signaling effectively inhibits cancer
stem like cell growth via metastasis, apoptosis and autophagy in HCC models.
AB - Cancer stem cells (CSCs), which are highly differentiated and self-renewing, play
an important role in the occurrence, therapeutic resistant and metastasis of
hepatacellular carcinoma (HCC). Oncolytic adenoviruses have targeted killing
effect on tumor cells, and are invoked as candidate drugs for cancer treatment.
We designed a dual-regulated oncolytic adenovirus Ad.wnt-E1A(?24bp)-TSLC1 that
targets Wnt and Rb signaling pathways respectively, and carries the tumor
suppressor gene, TSLC1. Previous studies have demonstrated that oncolytic
adenovirus mediated TSLC1can target liver cancer and exhibit significant
cytotoxicity. However, whether Ad.wnt-E1A(?24bp)-TSLC1 can effectively eliminate
liver CSCs remains to be explored. We first used the spheroid culture to enrich
the liver CSCs-like cells, and detected the self-renewal capacity,
differentiation, drug resistance and tumorigenicity. The results showed that Ad
wnt-E1A(?24bp)-TSLC1 could effectively lead to autophagic death. In addition,
recombinant adenovirus effectively induced the apoptosis, inhibit metastasis of
hepatic CSCs-like cells in vivo. Further animal experiments indicated that Ad-wnt
E1A(?24bp)-TSLC1could effectively inhibit the growth of transplanted tumor of
hepatic CSCs and prolong the survival time of mice. Therefore, the novel
oncolytic adenovirus Ad.wnt-E1A(?24bp)-TSLC1 has potential application as a
therapeutic target for HCC stem cells.
PMID- 28698143
TI - Snail transcription factor NLS and importin beta1 regulate the subcellular
localization of Cathepsin L and Cux1.
AB - Several recent studies have highlighted an additional unexpected localization and
site of action for Cathepsin L (Cat L) protease within the nucleus in breast,
colon and prostate cancer, however, its role in the nucleus was unclear. It was
proposed to mediate proteolytic processing of the transcription factor CCAAT
displacement protein/cut homeobox transcription factor (Cux1) from the full
length p200 isoform to generate the p110 and p90 isoforms, of which the p110
isoform was shown to act as a cell cycle regulator to accelerate entry into the S
phase. The p110 isoform has also been shown to bind to the promoter regions of
Snail and E-cadherin to activate Snail and inactivate E-cadherin transcription,
thus promoting epithelial mesenchymal transition (EMT). Mechanistic studies on
what drives Cat L nuclear localization have not been reported. Our hypothesis is
that Snail shuttles into the nucleus with Cat L through binding to importin-beta.
Snail knockdown with siRNA in MDA-MB-468 breast cancer cells led to nuclear to
cytoplasmic shuttling of Cat L and decreased levels of Cux1, while overexpression
of Snail in MCF-7 breast cancer cells or HEK-293 human embryonic kidney cells led
to increased nuclear expression of both Cat L and Cux1. Additionally, transient
transfection of Snail NLS mutants not only abrogated Snail nuclear localization
but also nuclear localization of Cat L and Cux1. Interestingly, importin beta1
knockdown with siRNA decreased Snail and Cux1 levels, as well as nuclear
localization of Cat L. Therefore, we show for the first time that the nuclear
localization of Cat L and its substrate Cux1can be positively regulated by Snail
NLS and importin beta1, suggesting that Snail, Cat L and Cux1 all utilize
importin beta1 for nuclear import.
PMID- 28698144
TI - Inhibiting glycogen synthase kinase-3 and transforming growth factor-beta
signaling to promote epithelial transition of human adipose mesenchymal stem
cells.
AB - BACKGROUND: This study was aimed to investigate the epithelial differentiation of
human adipose-derived mesenchymal stem cells (ADSCs) by inhibiting glycogen
synthase kinase-3 (GSK3) and transforming growth factor beta (TGFbeta) signaling.
METHODS AND RESULTS: STEMPRO human ADSCs at passage 2 were treated with CHIR99021
(GSK3 inhibitor), E-616452 (TGFbeta1 receptor kinase inhibitor), A-83-01 (TGFbeta
type 1 receptor inhibitor), valproic acid (histone deacetylase inhibitor),
tranylcypromine (monoamine oxidase inhibitor) and all-trans retinoic acid for 72
h. The mesenchymal-epithelial transition was shown by down-regulation of
mesenchymal genes (Slug, Zinc Finger E-box Binding Homeobox 1 ZEB1, integrin
alpha5 ITGA5 and vimentin VIM) and up-regulation of epithelial genes (E-cadherin,
Epithelial Cell Adhesion Molecule EpCAM, Zonula Occludens-1 ZO-1, occludin,
deltaN p63 deltaNp63, Transcription Factor 4 TCF4 and Twist Family bHLH
Transcription Factor TWIST), compared to untreated ADSCs. Cell morphology and
stress fiber pattern were examined and the treated cells became less migratory in
scratch wound closure assay. The formation of cell junction complexes was
observed under transmission electron microscopy. Global gene expression using
GeneChip(r) Human Genome U133 Array (Affymetrix) showed that the treatment up
regulated 540 genes (containing genes for cell cycle, cytoskeleton
reorganization, chemotaxis, epithelium development and regulation of cell
migration) and down-regulated 483 genes. CONCLUSION: Human ADSCs were transited
to epithelial lineage by inhibiting GSK3 and TGFbeta signaling. It can be an
adult stem cell source for epithelial cell-based therapy.
PMID- 28698145
TI - Increase in proteins involved in mitochondrial fission, mitophagy, proteolysis
and antioxidant response in type I endometrial cancer as an adaptive response to
respiratory complex I deficiency.
AB - Pathogenic mtDNA mutations associated with alterations of respiratory complex I,
mitochondrial proliferation (oncocytic-like phenotype) and increase in
antioxidant response were previously reported in type I endometrial carcinoma
(EC). To evaluate whether in the presence of pathogenic mtDNA mutations other
mitochondrial adaptive processes are triggered by cancer cells, the expression
level of proteins involved in mitochondrial dynamics, mitophagy, proteolysis and
apoptosis were evaluated in type I ECs harboring pathogenic mtDNA mutations and
complex I deficiency. An increase in the fission protein Drp1, in the mitophagy
protein BNIP3, in the mitochondrial protease CLPP, in the antioxidant and anti
apoptotic protein ALR and in Bcl-2 as well as a decrease in the fusion protein
Mfn2 were found in cancer compared to matched non malignant tissue. Moreover, the
level of these proteins was measured in type I EC, in hyperplastic (the
premalignant form) and in non malignant tissues to verify whether the altered
expression of these proteins is a common feature of endometrial cancer and of
hyperplastic tissue. This analysis confirmed in type I EC samples, but not in
hyperplasia, an alteration of the expression level of these proteins. These
results suggest that in this cancer mitochondrial fission, antioxidant and anti
apoptotic response may be activated, as well as the discharge of damaged
mitochondrial proteins as adaptation processes to mitochondrial dysfunction.
PMID- 28698146
TI - Epigenetic regulation of epithelial-mesenchymal transition by KDM6A histone
demethylase in lung cancer cells.
AB - Histone methylation is associated with various biological and pathological
processes including cancer development. KDM6A is a candidate tumor suppressor
gene that encodes a histone H3 lysine 27 (H3K27) demethylase. In this study, we
discovered that ectopic expression of KDM6A antagonized TGF-beta-induced
epithelial-mesenchymal transition (EMT) and cell migration of lung cancer cell
lines through its demethylase activity. KDM6A counteracted TGF-beta-dependent
changes in the expression of EMT-related genes such as CDH1/E-cadherin,
FN1/Fibronectin, ZEB family and microRNA-200 family. Mechanistic investigations
revealed that KDM6A inhibited the recruitment of EZH2 histone H3K27
methyltransferase and H3K27 methylation on the regulatory regions of the target
genes such as CDH1 and microRNA-200 family. Knockdown of KDM6A did not proceed
EMT by itself, but influenced the expression of specific target genes critical
for EMT, suggesting that endogenous KDM6A was involved in EMT-inducing
transcriptional program. This study demonstrated a novel regulatory role of KDM6A
histone demethylase in the epigenetic control of EMT process in lung cancer
cells.
PMID- 28698147
TI - RIP2 deficiency attenuates cardiac hypertrophy, inflammation and fibrosis in
pressure overload induced mice.
AB - Although the pathological cardiac hypertrophy presents a leading cause of
morbidity and mortality worldwide, our knowledge of the molecular mechanisms
underlying the disease is still poor. Here, we reported that receptor-interacting
serine/threonine-protein kinase 2 (RIP2), promoting pro-inflammatory gene
expression, enhanced the pathological cardiac hypertrophy in animals. The effects
of RIP2 on the cardiac hypertrophy triggered by pathological stimuli have not
been fully investigated. In our study, mice were subjected to aortic banding (AB)
surgery to explore the pathological, echocardiographic and molecular mechanisms.
RIP2 expressed highly in cardiomyocytes after AB operation in wild type (WT)
mice. RIP2-knockout (KO) attenuated cardiac hypertrophy, inflammation and
fibrosis in mice 4 weeks after AB-surgery. First, RIP2 knockout down-regulated
hypertrophic markers of atrial natriuretic peptide (ANP), brain natriuretic
peptide (BNP) and beta-myosin heavy chain (beta-MHC) in the heart of AB-operated
mice.in addition, RIP2-deficiency reduced toll-like receptor 4/myeloid
differentiation factor 88/nuclear factor kappa B (TLR4/MyD88/NF-kappaB)
activation, mitogen-activated protein kinases (MAPKs) phosphorylation and
transforming growth factor-beta1 (TGF-beta1)/SMADs expressions, contributing to
the suppression of inflammatory response and fibrosis, as further evidenced by
down-regulated pro-inflammatory cytokines, including Tumor necrosis factor-alpha
(TNF-alpha), interleukin (IL)-1beta, IL-6 and IL-18, as well as fibrosis markers
of Collagen I, Collagen III and alpha-smooth muscle actin (alpha-SMA). Taken
together, our data indicated that RIP2-deficience ameliorated cardiac
hypertrophy, inflammation and fibrosis through modulating multiple signaling
pathways.
PMID- 28698148
TI - Enzymatic characterization of a novel Xaa-Pro aminopeptidase XpmA from
Aspergillus oryzae expressed in Escherichia coli.
AB - Xaa-Pro aminopeptidases are peptidases responsible for the cleavage of any amino
acid N-terminally adjacent to a proline residue. We identified a gene encoding a
putative Xaa-Pro aminopeptidase in the genome of the filamentous fungus
Aspergillus oryzae (genome database number: AO090701000720) and named this gene
xpmA. We produced its enzyme in a C-terminally His6-tag-fused form in an
Escherichia coli expression system and purified it. The purified recombinant XpmA
(rXpmA) showed hydrolysis activity toward Xaa-Pro-oligopeptides, especially the
two dipeptides Ala-Pro and Phe-Pro. The molecular weight of rXpmA was estimated
to be 69 kDa by SDS-PAGE and 126 kDa by gel filtration, suggesting that it is a
homodimer. The enzyme was activated by various divalent metal ions such as Mn2+,
Co2+, and Mg2+; in particular, the enzyme activity was increased 27.6-times
relative to the no-addition control by 1 mM Mn2+. Additionally, 10 mM EDTA
suppressed its activity to 0.26-times of the control level. Therefore, rXpmA was
a metalloprotease. Optimal hydrolytic activity of rXpmA was observed at 50
degrees C and pH 8.5-9.0. The enzyme was stable up to 50 degrees C and from pH
4.0 to 11.0. rXpmA showed substrate inhibition by Leu-Pro, Ser-Pro and Arg-Pro at
concentrations over 4 mM, 10 mM, and 3 mM, respectively. NaCl increased the
enzyme activity in the concentration range 0.5-3.0 M, suggesting that the enzyme
is halophilic.
PMID- 28698149
TI - Gelatin modified lipid nanoparticles for anti- viral drug delivery.
AB - The major challenges to clinical application of zidovudine are its moderate
aqueous solubility and relative short half-life and serious side effects due to
frequent administrations. We investigated the preparation of zidovudine-loaded
nanoparticles based on lipids which were further modified with the polymer
gelatin. Formulation and stability of the modified nanoparticles were analysed
from the physico-chemical characterizations. The interactions of nanoparticles
with blood components were tested by haemolysis and aggregation studies. The drug
content and entrapment efficiencies were assessed by UV analysis. The effect of
nanoparticles on protein adsorption was assessed by native polyacrylamide gel
electrophoresis (PAGE). In vitro release studies showed a sustained release
profile of zidovudine. In vitro cytotoxicity and cellular uptake of the
zidovudine-loaded nanoparticles were performed in MCF-7 and neuro 2a brain cells.
The enhanced cellular internalization of drug loaded modified nanoparticles in
both the cell lines were revealed by fluorescence microscopy. Hence the present
study focuses on the feasibility of zidovudine-loaded polymer modified lipid
nanoparticles as carriers for safe and efficient HIV/AIDS therapy.
PMID- 28698150
TI - Freezing of gait is associated with cognitive impairment in patients with
Parkinson disease.
AB - OBJECTIVE: To explore whether the cognitive impairment is correlated with
freezing of gait (FOG) in patients with Parkinson disease (PD). METHODS: A total
of 186 patients with Parkinson disease (104 patients with FOG and 82 patients
with no clinical history of freezing behavior) and 125 healthy individuals were
selected for this study. Neuropsychological assessments, including the scales for
outcomes in Parkinson disease cognition, unified Parkinson's disease rating
scale, and Hamilton depression/anxiety rating scale etc., were applied to
evaluate the patients'cognitive functioning. RESULTS: We found that the scores of
Unified Parkinson's Disease Rating Scale (UPDRS) were significantly higher among
PD patients with FOG, compared with non-FOG group. We also showed that Mini
Mental State Examination score (MMSE) was lower among subjects with FOG than in
patients without FOG. Patients with FOG displayed lower Scales for OUTCOMES: in
Parkinson's Disease Cognition (SCOPA-COG) score than non-FOG patients. In
addition, significant higher Hamilton Anxiety Rating Scale (HAMD) scores were
found in patients with FOG than patients without FOG. Moreover, disease duration,
stage of the disease, the severity of motor symptom, increased depressive and
anxiety complaints measured by FOG questionnaire were significantly associated
with severity of FOG. Meanwhile, we also found that the score of Freezing of Gait
Questionnaire (FOGQ) score was negatively correlated with MMSE. CONCLUSION: Our
results demonstrated that FOG is related to impaired cognitive functions in PD
patients with FOG. The understanding of impaired cognitive functions in PD
patients with FOG can provide evidences for possible therapeutic interventions.
PMID- 28698151
TI - The effects of methamphetamine and buprenorphine, and their interaction on
anxiety-like behavior and locomotion in male rats.
AB - Methamphetamine (Meth) abuse and dependence are major global problems. Most of
previous studies showed that Meth is anxiogenic. While buprenorphine (Bup) is
used to treat anxiety-related behaviors, the effects of Meth in combination with
Bup on anxiety-like behavior are unclear. In this study, we examined the effects
of these drugs on anxiety-like behavior with the elevated plus maze (EPM) and
open field (OF) tests, which are widely used to assess anxiety-like behavior in
small rodents. Forty male Wistar rats were divided into four groups: sham, Meth,
Bup, and Bup+Meth. The groups were administered their assigned treatments for
7days. The time spent in the open arms, and number of total entries into the arms
(total activity) in the EPM were recorded. In addition, locomotor activity and
number of entrances into the center area in the OF were recorded. The 7-day
administration of Meth or Bup increased open arm exploration in the EPM. In
contrast, the combined administration of Bup and Meth had the opposite effects.
In addition, Meth and Bup had no effects on total and locomotor activity.
Furthermore, the rats in the Meth and Bup groups spent more time in the center of
the OF, while the group given both Bup and Meth spent less time in the center of
the OF. The administration of Meth and Bup alone was anxiolytic in rats, whereas
the coadministration of Bup and Meth was anxiogenic.
PMID- 28698152
TI - Novel functions of CCM1 delimit the relationship of PTB/PH domains.
AB - BACKGROUND: Three NPXY motifs and one FERM domain in CCM1 makes it a versatile
scaffold protein for tethering the signaling components together within the CCM
signaling complex (CSC). The cellular role of CCM1 protein remains inadequately
expounded. Both phosphotyrosine binding (PTB) and pleckstrin homology (PH)
domains were recognized as structurally related but functionally distinct
domains. METHODS: By utilizing molecular cloning, protein binding assays and RT
qPCR to identify novel cellular partners of CCM1 and its cellular expression
patterns; by screening candidate PTB/PH proteins and subsequently structurally
simulation in combining with current X-ray crystallography and NMR data to
defined the essential structure of PTB/PH domain for NPXY-binding and the
relationship among PTB, PH and FERM domain(s). RESULTS: We identified a group of
28 novel cellular partners of CCM1, all of which contain either PTB or PH
domain(s), and developed a novel classification system for these PTB/PH proteins
based on their relationship with different NPXY motifs of CCM1. Our results
demonstrated that CCM1 has a wide spectrum of binding to different PTB/PH
proteins and perpetuates their specificity to interact with certain PTB/PH
domains through selective combination of three NPXY motifs. We also demonstrated
that CCM1 can be assembled into oligomers through intermolecular interaction
between its F3 lobe in FERM domain and one of the three NPXY motifs. Despite
being embedded in FERM domain as F3 lobe, F3 module acts as a fully functional PH
domain to interact with NPXY motif. The most salient feature of the study was
that both PTB and PH domains are structurally and functionally comparable,
suggesting that PTB domain is likely evolved from PH domain with polymorphic
structural additions at its N-terminus. CONCLUSIONS: A new beta1A-strand of the
PTB domain was discovered and new minimum structural requirement of PTB/PH domain
for NPXY motif-binding was determined. Based on our data, a novel theory of
structure, function and relationship of PTB, PH and FERM domains has been
proposed, which extends the importance of the NPXY-PTB/PH interaction on the CSC
signaling and/or other cell receptors with great potential pointing to new
therapeutic strategies. GENERAL SIGNIFICANCE: The study provides new insight into
the structural characteristics of PTB/PH domains, essential structural elements
of PTB/PH domain required for NPXY motif-binding, and function and relationship
among PTB, PH and FERM domains.
PMID- 28698153
TI - Curcumin prevents cisplatin-induced renal alterations in mitochondrial
bioenergetics and dynamic.
AB - Cisplatin is widely used as chemotherapeutic agent for treatment of diverse types
of cancer, however, acute kidney injury (AKI) is an important side effect of this
treatment. Diverse mechanisms have been involved in cisplatin-induced AKI, such
as oxidative stress, apoptosis and mitochondrial damage. On the other hand,
curcumin is a polyphenol extracted from the rhizome of Curcuma longa L. Previous
studies have shown that curcumin protects against the cisplatin-induced AKI;
however, it is unknown whether curcumin can reduce alterations in mitochondrial
bioenergetics and dynamic in this model. It was found that curcumin prevents
cisplatin-induced: (a) AKI and (b) alterations in the following mitochondrial
parameters: bioenergetics, ultrastructure, hydrogen peroxide production and
dynamic. In fact, curcumin prevented the increase of mitochondrial fission 1
protein (FIS1), the decrease of optic atrophy 1 protein (OPA1) and the decrease
of NAD+-dependent deacetylase sirtuin-3 (SIRT3), a mitochondrial dynamic
regulator as well as the increase in the mitophagy associated proteins parkin and
phosphatase and tensin homologue (PTEN)-induced putative kinase protein 1
(PINK1). In conclusion, the protective effect of curcumin in cisplatin-induced
AKI was associated with the prevention of the alterations in mitochondrial
bioenergetics, ultrastructure, redox balance, dynamic, and SIRT3 levels.
PMID- 28698154
TI - Panax ginseng and Panax quinquefolius: From pharmacology to toxicology.
AB - The use of Panax ginseng and Panax quinquefolius in traditional Chinese medicine
dates back to about 5000 years ago thanks to its several beneficial and healing
properties. Over the past few years, extensive preclinical and clinical evidence
in the scientific literature worldwide has supported the beneficial effects of P.
ginseng and P. quinquefolius in significant central nervous system, metabolic,
infectious and neoplastic diseases. There has been growing research on ginseng
because of its favorable pharmacokinetics, including the intestinal
biotransformation which is responsible for the processing of ginsenosides -
contained in the roots or extracts of ginseng - into metabolites with high
pharmacological activity and how such principles act on numerous cell targets.
The aim of this review is to provide a simple and extensive overview of the
pharmacokinetics and pharmacodynamics of P. ginseng and P. quinquefolius,
focusing on the clinical evidence which has shown particular effectiveness in
specific diseases, such as dementia, diabetes mellitus, respiratory infections,
and cancer. Furthermore, the review will also provide data on toxicological
factors to support the favorable safety profile of these medicinal plants.
PMID- 28698155
TI - In silico approach to safety of botanical dietary supplement ingredients
utilizing constituent-level characterization.
AB - Botanicals used in dietary supplements industry can have toxicology concerns
related to endpoint gaps that cannot be fully resolved by a history of use, or
existence of conflicting safety data. However, traditional toxicological studies
on botanicals are scientifically and pragmatically challenging due to testing of
complex mixtures of constituents, cost, time, and animal usage. Alternatively, we
developed an in silico decision-tree approach to address data gaps and inform
need for further studies by toxicologically evaluating the chemical composition
of botanicals. Following advanced multi-detector analytical characterization of a
botanical, each chemical constituent is: (a.) quantitatively benchmarked against
similar constituents in commonly consumed foods or botanicals with well
established safety profiles, (b.) systematically evaluated for toxicity data
utilizing structure-activity relationships, and, (c.) compared to established
thresholds of toxicological concern in absence of safety data or structural
analogs. Finally, where safety endpoint gaps are identified which cannot be
resolved without additional in vitro or in vivo studies, the botanical
compositional data are critical to inform on study design. Results with three
herbal preparations demonstrate the utility of this novel approach to identify
potential hazards and establish safe human use levels for botanicals in a cost
efficient and informative manner that minimizes animal use.
PMID- 28698156
TI - Disruption of predicted dengue virus type 3 major outbreak cycle coincided with
switching of the dominant circulating virus genotype.
AB - Dengue is hyperendemic in most of Southeast Asia. In this region, all four dengue
virus serotypes are persistently present. Major dengue outbreak cycle occurs in a
cyclical pattern involving the different dengue virus serotypes. In Malaysia,
since the 1980s, the major outbreak cycles have involved dengue virus type 3
(DENV3), dengue virus type 1 (DENV1) and dengue virus type 2 (DENV2), occurring
in that order (DENV3/DENV1/DENV2). Only limited information on the DENV3 cycles,
however, have been described. In the current study, we examined the major
outbreak cycle involving DENV3 using data from 1985 to 2016. We examined the
genetic diversity of DENV3 isolates obtained during the period when DENV3 was the
dominant serotype and during the inter-dominant transmission period. Results
obtained suggest that the typical DENV3/DENV1/DENV2 cyclical outbreak cycle in
Malaysia has recently been disrupted. The last recorded major outbreak cycle
involving DENV3 occurred in 2002, and the expected major outbreak cycle involving
DENV3 in 2006-2012 did not materialize. DENV genome analyses revealed that DENV3
genotype II (DENV3/II) was the predominant DENV3 genotype (67%-100%) recovered
between 1987 and 2002. DENV3 genotype I (DENV3/I) emerged in 2002 followed by the
introduction of DENV3 genotype III (DENV3/III) in 2008. These newly emerged DENV3
genotypes replaced DENV3/II, but there was no major upsurge of DENV3 cases that
accompanied the emergence of these viruses. DENV3 remained in the background of
DENV1 and DENV2 until now. Virus genome sequence analysis suggested that
intrinsic differences within the different dengue virus genotypes could have
influenced the transmission efficiency of DENV3. Further studies and continuous
monitoring of the virus are needed for better understanding of the DENV
transmission dynamics in hyperendemic regions.
PMID- 28698157
TI - Prevalence, molecular epidemiology, and zoonotic potential of Entamoeba spp. in
nonhuman primates in China.
AB - Amebiasis is a major public-health concern. It has a global distribution, and is
listed as the third leading parasitic cause of human mortality. To survey the
prevalence and assess the potential zoonotic transmission of Entamoeba spp. in
nonhuman primates (NHPs) in China, 2688 fresh fecal specimens were collected from
NHPs reared in farms or zoos/parks or free ranging in 13 districts. The overall
prevalence of Entamoeba spp. infection determined with microscopy analysis was
39.4% (1059/2688). Higher infection rates were detected in the free ranging group
(41.1%, 169/411) and in animals <1year old (58.7%, 556/947). Gene fragments were
successfully amplified 463 (87.2%) out of the 531 selected specimens
(approximately half of the total microscopy-positive specimens). Polymerase chain
reaction (PCR) amplification identified 386 (83.4%) Entamoeba dispar and 287
(62.0%) E. coli infections, and among these, 210 (45.4%) were mixed infections.
And that the E. dispar and E. coli had also been detected in humans. In
phylogenetic analysis, the E. dispar and E. coli sequences clustered with
reference E. dispar and E. coli, respectively. In conclusion, nonhuman primates
infected with Entamoeba species, with high prevalence and zoonotic potential,
should be considered when evaluating the maintenance of Entamoeba spp. and its
transmission between animal reservoirs and humans.
PMID- 28698158
TI - Pigment epithelium derived factor play a positive role in bone mineralization of
osteoblasts derived from diabetic patients.
AB - Pigment epithelium-derived factor (PEDF) is a multifunctional secreted protein
which plays important role in anti-angiogenic, anti-tumorigenic, as well as
involves in the metabolism and regeneration of bone. In this study, our aim is to
investigate the role of PEDF in regulating mineralization of osteoblasts from
diabetic patients (DP). We isolated and cultured osteoblasts derived from DP and
non-diabetic patients (NDP), in order to analyze the variable differences via
gene expression and calcification assay in vitro. Gene expression analysis and
alizarin red S staining revealed that osteoblasts from DP exhibited defective
mineralization. PEDF and vascular endothelial growth factor (VEGF) levels were
lower in osteoblasts from DP than those from NDP. Interestingly, exogenous PEDF
could upregulate the gene expression levels of VEGF and osteoblast-related genes,
further to restore mineralization ability in osteoblasts from DP. Our results
demonstrated that PEDF played a positive role in maintaining bone development in
diabetic osteoblasts, therefore, we confidently believe that PEDF may be a
promising cytokine to consider in development of treatments for diabetic bone
diseases.
PMID- 28698159
TI - Identification of novel and hotspot mutations in the channel domain of ITPR1 in
two patients with Gillespie syndrome.
AB - ITPR1 encodes an intracellular receptor for inositol 1,4,5-trisphosphate (InsP3)
which is highly expressed in the cerebellum and is involved in the regulation of
Ca2+ homeostasis. Missense mutations in the InsP3-binding domain (IRBIT) of ITPR1
are frequently associated with early onset cerebellar atrophy. Gillespie syndrome
is characterized by congenital ataxia, mild to moderate intellectual disability
and iris hypoplasia. Dominant or recessive ITPR1 mutations have been recently
associated with this form of syndromic ataxia. We performed next generation
sequencing in two simplex families with Gillespie syndrome and identified de novo
pathological mutations localized in the C-terminal channel domain of ITPR1 in
both patients: a recurrent deletion (p.Lys2596del) and a novel missense mutation
(p.Asn2576Ile) close to a point of constriction in the Ca2+ pore. Our study
expands the mutational spectrum of ITPR1 and confirms that ITPR1 screening should
be implemented in patients with congenital cerebellar ataxia with or without iris
hypoplasia.
PMID- 28698160
TI - Investigating the regulatory roles of the microRNAs and the Argonaute 1-enriched
small RNAs in plant metabolism.
AB - The biological roles of small RNAs (sRNAs) in metabolic processes are emerging.
However, a systemic study is needed to investigate the wide-spread involvement of
the sRNAs in plant metabolism. By using the metabolism-related transcripts
retrieved from the public database Plant Metabolic Network, and the publicly
available sRNA high-throughput sequencing data, large-scale target identification
was performed for microRNAs (miRNAs) and Argonaute 1 (AGO1)-enriched sRNAs in
Arabidopsis (Arabidopsis thaliana) and rice (Oryza sativa). Based on the publicly
available degradome sequencing data, 200 miRNA/sRNA-target pairs involving 19
miRNAs, 111 AGO1-enriched sRNAs and 58 target transcripts in Arabidopsis, and 151
pairs involving 62 miRNAs, 33 AGO1-enriched sRNAs and 69 target transcripts in
rice were identified. After considering protein-protein interactions for the
above identified target genes, a total of 251 pairs involving 21 miRNAs, 120 AGO1
enriched sRNAs and 75 target transcripts exist within the regulatory network of
Arabidopsis, and 168 pairs involving 64 miRNAs, 38 AGO1-enriched sRNAs and 80
target transcripts exist in rice. Based on GO (Gene Ontology) term enrichment
analysis, the targets within the networks of both plants are enriched in
"metabolic process" and "catalytic activity", pointing to the high relevance of
the established networks to metabolism. Several functionally conserved
subnetworks were identified between the two plant species. Our study provides a
basis for studies on metabolism-related sRNAs in plants.
PMID- 28698161
TI - Evolutionary conservation and expression of miR-10a-3p in olive flounder and rock
bream.
AB - MicroRNAs (miRNAs) are small non-coding RNAs (ncRNAs) that mainly bind to the
seed sequences located within the 3' untranslated region (3' UTR) of target
genes. They perform an important biological function as regulators of gene
expression. Different genes can be regulated by the same miRNA, whilst different
miRNAs can be regulated by the same genes. Here, the evolutionary conservation
and expression pattern of miR-10a-3p in olive flounder and rock bream was
examined. Binding sites (AAAUUC) to seed region of the 3' UTR of target genes
were highly conserved in various species. The expression pattern of miR-10a-3p
was ubiquitous in the examined tissues, whilst its expression level was decreased
in gill tissues infected by viral hemorrhagic septicemia virus (VHSV) compared to
the normal control. In the case of rock bream, the spleen, kidney, and liver
tissues showed dominant expression levels of miR-10a-3p. Only the liver tissues
in the rock bream samples infected by the iridovirus indicated a dominant miR-10a
3p expression. The gene ontology (GO) analysis of predicted target genes for miR
10a-3p revealed that multiple genes are related to binding activity, catalytic
activity, cell components as well as cellular and metabolic process. Overall the
results imply that the miR-10a-3p could be used as a biomarker to detect VHSV
infection in olive flounder and iridovirus infection in rock bream. In addition,
the data provides fundamental information for further study of the complex
interaction between miR-10a-3p and gene expression.
PMID- 28698162
TI - Galleria mellonella is low cost and suitable surrogate host for studying
virulence of human pathogenic Vibrio cholerae.
AB - Vibrio cholerae causes a severe diarrheal disease affecting millions of people
worldwide, particularly in low income countries. V. cholerae successfully persist
in aquatic environment and its pathogenic strains results in sever enteric
disease in humans. This dual life style contributes towards its better survival
and persistence inside host gut and in the environment. Alternative animal
replacement models are of great value in studying host-pathogen interaction and
for quick screening of various pathogenic strains. One such model is Galleria
mellonella, a wax moth which has a complex innate immune system and here we
investigate its suitability as a model for clinical human isolates of O1 El TOR,
Ogawa serotype belonging to two genetically distinct subclades found in Pakistan
(PSC-1 and PSC-2). We demonstrate that the PSC-2 strain D59 frequently isolated
from inland areas, was more virulent than PSC-1 strain K7 mainly isolated from
coastal areas (p=0.0001). In addition, we compared the relative biofilm
capability of the representative strains as indicators of their survival and
persistence in the environment and K7 showed enhanced biofilm forming
capabilities (p=0.004). Finally we present the annotated genomes of the strains
D59 and K7, and compared them with the reference strain N16961.
PMID- 28698163
TI - Selective effect of hydroxyapatite nanoparticles on osteoporotic and healthy bone
formation correlates with intracellular calcium homeostasis regulation.
AB - : Adequate bone substitutes osseointegration has been difficult to achieve in
osteoporosis. Hydroxyapatite of the osteoporotic bone, secreted by pathologic
osteoblasts, had a smaller crystal size and lower crystallinity than that of the
normal. To date, little is known regarding the interaction of synthetic
hydroxyapatite nanoparticles (HANPs) with osteoblasts born in bone rarefaction.
The present study investigated the biological effects of HANPs on osteoblastic
cells derived from osteoporotic rat bone (OVX-OB), in comparison with the healthy
ones (SHM-OB). A selective effect of different concentrations of HANPs on the two
cell lines was observed that the osteoporotic osteoblasts had a higher tolerance.
Reductions in cell proliferation, ALP activity, collagen secretion and
osteoblastic gene expressions were found in the SHM-OB when administered with
HANPs concentration higher than 25ug/ml. In contrast, those of the OVX-OB
suffered no depression but benefited from 25 to 250ug/ml HANPs in a dose
dependent manner. We demonstrated that the different effects of HANPs on
osteoblasts were associated with the intracellular calcium influx into the
endoplasmic reticulum. The in vivo bone defect model further confirmed that, with
a critical HANPs concentration administration, the osteoporotic rats had more and
mechanically matured new bone formation than the non-treated ones, whilst the
sham rats healed no better than the natural healing control. Collectively, the
observed epigenetic regulation of osteoblastic cell function by HANPs has
significant implication on defining design parameters for a potential therapeutic
use of nanomaterials. STATEMENT OF SIGNIFICANCE: In this study, we investigated
the biological effects of hydroxyapatite nanoparticles (HANPs) on osteoporotic
rat bone and the derived osteoblast. Our findings revealed a previously
unrecognized phenomenon that the osteoporotic individuals could benefit from
higher concentrations of HANPs, as compared with the healthy individuals. The in
vivo bone defect model confirmed that, with a critical HANPs concentration
administration, the osteoporotic rats had more mechanically matured new bone
formation than the non-treated ones, whilst the sham rats healed no better than
the natural healing control. The selective effect of HANPs might be associated
with the intracellular calcium influx into the endoplasmic reticulum.
Collectively, the observed epigenetic regulation by HANPs has significant
implication on defining design parameters for a potential therapeutic use of
nanomaterials in a pathological condition.
PMID- 28698164
TI - A case of bullous pemphigoid presenting with severe oedema of the hands during
recurrence.
PMID- 28698165
TI - A case of annular elastolytic giant cell granuloma on unusual sites requiring the
differential diagnosis of necrobiosis lipoidica.
PMID- 28698166
TI - Linear IgA bullous dermatosis in a two-year-old child: possible association with
aspirin.
PMID- 28698167
TI - Use of a Connected Glucose Meter and Certified Diabetes Educator Coaching to
Decrease the Likelihood of Abnormal Blood Glucose Excursions: The Livongo for
Diabetes Program.
AB - BACKGROUND: The Livongo for Diabetes Program offers members (1) a cellular
technology-enabled, two-way messaging device that measures blood glucose (BG),
centrally stores the glucose data, and delivers messages back to the individual
in real time; (2) unlimited BG test strips; and (3) access to a diabetes coaching
team for questions, goal setting, and automated support for abnormal glucose
excursions. The program is sponsored by at-risk self-insured employers, health
plans and provider organizations where it is free to members with diabetes or it
is available directly to the person with diabetes where they cover the cost.
OBJECTIVE: The objective of our study was to evaluate BG data from 4544
individuals with diabetes who were enrolled in the Livongo program from October
2014 through December 2015. METHODS: Members used the Livongo glucose meter to
measure their BG levels an average of 1.8 times per day. We estimated the
probability of having a day with a BG reading outside of the normal range (70-180
mg/dL, or 3.9-10.0 mmol/L) in months 2 to 12 compared with month 1 of the
program, using individual fixed effects to control for individual
characteristics. RESULTS: Livongo members experienced an average 18.4% decrease
in the likelihood of having a day with hypoglycemia (BG <70 mg/dL) and an average
16.4% decrease in hyperglycemia (BG >180 mg/dL) in months 2-12 compared with
month 1 as the baseline. The biggest impact was seen on hyperglycemia for
nonusers of insulin. We do not know all of the contributing factors such as
medication or other treatment changes during the study period. CONCLUSIONS: These
findings suggest that access to a connected glucose meter and certified diabetes
educator coaching is associated with a decrease in the likelihood of abnormal
glucose excursions, which can lead to diabetes-related health care savings.
PMID- 28698168
TI - A Self-Regulation-Based eHealth Intervention to Promote a Healthy Lifestyle:
Investigating User and Website Characteristics Related to Attrition.
AB - BACKGROUND: eHealth interventions can reach large populations and are effective
in increasing physical activity (PA) and fruit and vegetable intake.
Nevertheless, the effects of eHealth interventions are overshadowed by high
attrition rates. Examining more closely when users decide to leave the
intervention can help eHealth developers to make informed decisions about which
intervention components should be reshaped or simply removed. Investigating which
users are more likely to quit an intervention can inform developers about whether
and how their intervention should be adapted to specific subgroups of users.
OBJECTIVE: This study investigated the pattern of attrition in a Web-based
intervention to increase PA, fruit, and vegetable intake. The first aim was to
describe attrition rates according to different self-regulation components. A
second aim was to investigate whether certain user characteristics are predictors
for start session completion, returning to a follow-up session and intervention
completion. METHODS: The sample consisted of 549 adults who participated in an
online intervention, based on self-regulation theory, to promote PA and fruit and
vegetable intake, called "MyPlan 1.0." Using descriptive analysis, attrition was
explored per self-regulation component (eg, action planning and coping planning).
To identify which user characteristics predict completion, logistic regression
analyses were conducted. RESULTS: At the end of the intervention program, there
was an attrition rate of 78.2% (330/422). Attrition rates were very similar for
the different self-regulation components. However, attrition levels were higher
for the fulfillment of questionnaires (eg, to generate tailored feedback) than
for the more interactive components. The highest amount of attrition could be
observed when people were asked to make their own action plan. There were no
significant predictors for first session completion. Yet, two subgroups had a
lower chance to complete the intervention, namely male users (OR: 2.24, 95%
CI=1.23-4.08) and younger adults (OR: 1.02, 95% CI=1.00-1.04). Furthermore,
younger adults were less likely to return to the website for the first follow-up
after one week (OR: 1.03, 95% CI=1.01-1.04). CONCLUSIONS: This study informs us
that eHealth interventions should avoid the use of extensive questionnaires and
that users should be provided with a rationale for several components (eg, making
an action plan and completing questions). Furthermore, future interventions
should focus first on motivating users for the behavior change before guiding
them through action planning. Though, this study provides no evidence for removal
of one of the self-regulation techniques based on attrition rates. Finally,
strong efforts are needed to motivate male users and younger adults to complete
eHealth interventions.
PMID- 28698169
TI - Effectiveness of Digital Medicines to Improve Clinical Outcomes in Patients with
Uncontrolled Hypertension and Type 2 Diabetes: Prospective, Open-Label, Cluster
Randomized Pilot Clinical Trial.
AB - BACKGROUND: Hypertension and type 2 diabetes mellitus are major modifiable risk
factors for cardiac, cerebrovascular, and kidney diseases. Reasons for poor
disease control include nonadherence, lack of patient engagement, and therapeutic
inertia. OBJECTIVE: The aim of this study was to assess the impact on clinic
measured blood pressure (BP) and glycated hemoglobin (HbA1c) using a digital
medicine offering (DMO) that measures medication ingestion adherence, physical
activity, and rest using digital medicines (medication taken with ingestible
sensor), wearable sensor patches, and a mobile device app. METHODS: Participants
with elevated systolic BP (SBP >=140 mm Hg) and HbA1c (>=7%) failing
antihypertensive (>=2 medications) and oral diabetes therapy were enrolled in
this three-arm, 12-week, cluster-randomized study. Participants used DMO
(includes digital medicines, the wearable sensor patch, and the mobile device
app) for 4 or 12 weeks or received usual care based on site randomization.
Providers in the DMO arms could review the DMO data via a Web portal. In all
three arms, providers were instructed to make medical decisions (medication
titration, adherence counseling, education, and lifestyle coaching) on all
available clinical information at each visit. Primary outcome was change in SBP
at week 4. Other outcomes included change in SBP and HbA1c at week 12, and low
density lipoprotein cholesterol (LDL-C) and diastolic blood pressure (DBP) at
weeks 4 and 12, as well as proportion of patients at BP goal (<140/90 mm Hg) at
weeks 4 and 12, medical decisions, and medication adherence patterns. RESULTS:
Final analysis included 109 participants (12 sites; age: mean 58.7, SD years;
female: 49.5%, 54/109; Hispanic: 45.9%, 50/109; income <= US $20,000: 56.9%,
62/109; and <= high school education: 52.3%, 57/109). The DMO groups had 80
participants (7 sites) and usual care had 29 participants (5 sites). At week 4,
DMO resulted in a statistically greater SBP reduction than usual care (mean
21.8, SE 1.5 mm Hg vs mean -12.7, SE 2.8 mmHg; mean difference -9.1, 95% CI -14.0
to -3.3 mm Hg) and maintained a greater reduction at week 12. The DMO groups had
greater reductions in HbA1c, DBP, and LDL-C, and a greater proportion of
participants at BP goal at weeks 4 and 12 compared with usual care. The DMO
groups also received more therapeutic interventions than usual care. Medication
adherence was >=80% while using the DMO. The most common adverse event was a self
limited rash at the wearable sensor site (12%, 10/82). CONCLUSIONS: For patients
failing hypertension and diabetes oral therapy, this DMO, which provides dose-by
dose feedback on medication ingestion adherence, can help lower BP, HbA1c, and
LDL-C, and promote patient engagement and provider decision making. TRIAL
REGISTRATION: Clinicaltrials.gov NCT02827630;
https://clinicaltrials.gov/show/NCT02827630 (Archived by WebCite at
http://www.webcitation.org/6rL8dW2VF).
PMID- 28698170
TI - Content Analysis of Smartphone Apps for Smoking Cessation in China: Empirical
Study.
AB - BACKGROUND: With 360 million smokers, China consumes more cigarettes than any
other country in the world. Given that 620 million Chinese own smartphones,
smartphone apps for smoking cessation are increasingly used in China to help
smokers quit. OBJECTIVE: This study analyzed and evaluated the contents of all
smoking cessation apps (iOS and Android) available in China, applying the China
Clinical Smoking Cessation Guideline (CCSCG; identical to the US Clinical
Practice Guideline for Treating Tobacco Use and Dependence) as a framework for
analysis. METHODS: We conducted a content analysis of Chinese Android and iOS
smoking cessation apps (N=64) designed to assist users in quitting smoking. Each
app was independently coded by two raters for its approach to smoking cessation
and adherence to the CCSCG. We also recorded the features of smoking cessation
apps (eg, release date, size, frequency of downloads, user ratings, type, quality
scores by raters, and designers). Linear regression was used to test predictors
of popularity and user-rated quality. RESULTS: Chinese smoking cessation apps
have low levels of adherence to guidelines, with an average score of 11.1 for
Android and 14.6 for iOS apps on a scale of 0 to 46. There was no significant
association between popularity, user rating, and the characteristics of apps.
However, there was a positive relationship between popularity, user rating, and
adherence score. CONCLUSIONS: Chinese apps for smoking cessation have low levels
of adherence to standard clinical practice guidelines. New apps need be developed
and existing apps be revised following evidence-based principles in China.
PMID- 28698171
TI - Natural Compounds for the Treatment of Psoriatic Arthritis: A Proposal Based on
Multi-Targeted Osteoclastic Regulation and on a Preclinical Study.
AB - BACKGROUND: Psoriatic arthritis (PsA) is a chronic inflammatory arthritis
affecting approximately 2% to 3% of the population globally, and is characterized
by both peripheral articular manifestations and axial skeletal involvement.
Conventional therapies for PsA have not been fully satisfactory, though natural
products (NPs) have been shown to be highly effective and represent important
treatment options for psoriasis. PsA is a multigenic autoimmune disease with both
environmental and genetic factors contributing to its pathogenesis. Accordingly,
it is likely that the use of natural compounds with a multi-targeted approach
will enable us to develop better therapies for PsA and related disorders.
OBJECTIVE: PsA, either on joint damage or on bone erosion, has been shown to
respond to anti-psoriatic pharmacotherapy (APP), APP-like NPs, and their natural
compounds. This study aims to uncover specific natural compounds for improved PsA
remedies. Specifically, by targeting bone erosion caused by increased
osteoclastic bone resorption, we aim to predict the key signaling pathways
affected by natural compounds. Further, the study will explore their anti
arthritis effects using an in silico, in vitro, and in vivo approach. Following
the signaling pathway prediction, a preclinical efficacy study on animal models
will be undertaken. Collectively, this work will discover lead compounds with
improved therapeutic effects on PsA. METHODS: We hypothesize that 9 potential APP
like NPs will have therapeutic effects on arthritis via the modulation of
osteoclast bone resorption and signaling pathways. For in silico identification,
the Latin name of each NP will be identified using the Encyclopedia of
Traditional Chinese Medicine (Encyclopedia of TCM). The biological targets of NPs
will be predicted or screened using the Herbal Ingredients' Targets (HIT)
database. With the designed search terms, DrugBank will be used to further filter
the above biological targets. Protein ANnotation THrough Evolutionary
Relationship (PANTHER) will be used to predict the pathways of the natural
compound sources. Subsequently, an in vitro sample preparation including
extraction, fractionation, isolation, purification, and bioassays with high-speed
counter-current chromatography-high-performance liquid chromatography-diode array
detection (HSCCC-HPLC-DAD) will be carried out for each identified natural
source. In vitro investigations into the effect of NPs on osteoclast signaling
pathways will be performed. The experimental methods include cell viability
assays, osteoclastogenesis and resorption pit assays, quantitative reverse
transcription polymerase chain reaction (RT-PCR), western blot, and luciferase
reporter gene assays. Finally, an in vivo preclinical efficacy on a collagen
induced arthritis rat model will be carried out using a treatment group (n=10), a
control group (n=10), and a non-arthritis group (n=10). Main outcome measure
assessments during intervention include daily macroscopic scores and a digital
calipers measurement. Post-treatment tissue measurements will be analyzed by
serological testing, radiographic imaging, and histopathological assessment.
RESULTS: Studies are currently underway to evaluate the in silico data and the in
vitro effects of compounds on osteoclastogenesis and bone resorption. The
preclinical study is expected to start a year following completion of the in
silico analysis. CONCLUSIONS: The in silico rapid approach is proposed as a more
general method for adding value to the results of a systematic review of NPs.
More importantly, the proposed study builds on a multi-targeted approach for the
identification of natural compounds for future drug discovery. This innovative
approach is likely to be more precise, efficient, and compatible to identify the
novel natural compounds for effective treatment of PsA.
PMID- 28698174
TI - Out of stock: summit highlights global lack of access to contraceptives.
PMID- 28698173
TI - Interferon Regulatory Factor 5 Controls Necrotic Core Formation in
Atherosclerotic Lesions by Impairing Efferocytosis.
AB - BACKGROUND: Myeloid cells are central to atherosclerotic lesion development and
vulnerable plaque formation. Impaired ability of arterial phagocytes to uptake
apoptotic cells (efferocytosis) promotes lesion growth and establishment of a
necrotic core. The transcription factor interferon regulatory factor (IRF)-5 is
an important modulator of myeloid function and programming. We sought to
investigate whether IRF5 affects the formation and phenotype of atherosclerotic
lesions. METHODS: We investigated the role of IRF5 in atherosclerosis in 2
complementary models. First, atherosclerotic lesion development in hyperlipidemic
apolipoprotein E-deficient (ApoE-/-) mice and ApoE-/- mice with a genetic
deletion of IRF5 (ApoE-/-Irf5-/-) was compared and then lesion development was
assessed in a model of shear stress-modulated vulnerable plaque formation.
RESULTS: Both lesion and necrotic core size were significantly reduced in ApoE-/
Irf5-/- mice compared with IRF5-competent ApoE-/- mice. Necrotic core size was
also reduced in the model of shear stress-modulated vulnerable plaque formation.
A significant loss of CD11c+ macrophages was evident in ApoE-/-Irf5-/- mice in
the aorta, draining lymph nodes, and bone marrow cell cultures, indicating that
IRF5 maintains CD11c+ macrophages in atherosclerosis. Moreover, we revealed that
the CD11c gene is a direct target of IRF5 in macrophages. In the absence of IRF5,
CD11c- macrophages displayed a significant increase in expression of the
efferocytosis-regulating integrin-beta3 and its ligand milk fat globule-epidermal
growth factor 8 protein and enhanced efferocytosis in vitro and in situ.
CONCLUSIONS: IRF5 is detrimental in atherosclerosis by promoting the maintenance
of proinflammatory CD11c+ macrophages within lesions and controlling the
expansion of the necrotic core by impairing efferocytosis.
PMID- 28698175
TI - Echocardiographic aortic valve calcification and outcomes in women and men with
aortic stenosis.
AB - OBJECTIVE: Sex differences in risk factors of aortic valve calcification (AVC) by
echocardiography have not been reported from a large prospective study in aortic
stenosis (AS). METHODS: AVC was assessed using a prognostically validated visual
score and grouped into none/mild or moderate/severe AVC in 1725 men and women
with asymptomatic AS in the Simvastatin Ezetimibe in Aortic Stenosis study. The
severity of AS was assessed by the energy loss index (ELI) taking pressure
recovery in the aortic root into account. RESULTS: More men than women had
moderate/severe AVC at baseline despite less severe AS by ELI (p<0.01).
Moderate/severe AVC at baseline was independently associated with lower aortic
compliance and more severe AS in both sexes, and with increased high-sensitive C
reactive protein (hs-CRP) only in men (all p<0.01). In Cox regression analyses,
moderate/severe AVC at baseline was associated with a 2.5-fold (95% CI 1.64 to
3.80) higher hazard rate of major cardiovascular events in women, and a 2.2-fold
higher hazard rate in men (95% CI 1.54 to 3.17) (both p<0.001), after adjustment
for age, hypertension, study treatment, aortic compliance, left ventricular (LV)
mass and systolic function, AS severity and hs-CRP. Moderate/severe AVC at
baseline also predicted a 1.8-fold higher hazard rate of all-cause mortality in
men (95% CI 1.04 to 3.06, p<0.05) independent of age, AS severity, LV mass and
aortic compliance, but not in women. CONCLUSION: In conclusion, AVC scored by
echocardiography has sex-specific characteristics in AS. Moderate/severe AVC is
associated with higher cardiovascular morbidity in both sexes, and with higher
all-cause mortality in men. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov
identifier: NCT00092677.
PMID- 28698176
TI - Formal firearm training among adults in the USA: results of a national survey.
AB - Despite broad support for policies requiring that prospective firearm owners
receive training before acquiring a firearm, little is known about the scope and
content of firearm training in the USA. Nationally representative surveys
conducted in 1994 estimated that 56%-58% of the US firearm owners had received
formal firearm training. We conducted a nationally representative survey in 2015
(n=3932; completion proportion=55%) to update those estimates and characterise
training contents. 61% of firearm owners and 14% of non-owners living with a
firearm owner reported having received formal firearm training. The most commonly
reported combination of training topics was safe handling, safe storage and
preventing accidents. 15% of firearm owners reported that their training included
information about suicide prevention. The proportion of the US firearm owners
with formal firearm training has not meaningfully changed since two decades ago.
Training programme contents vary widely. Efforts to standardise and evaluate the
effectiveness of firearm training are warranted.
PMID- 28698177
TI - Independence is critical for shared decision making.
PMID- 28698178
TI - Occupational and leisure-time physical activity and risk of disability pension:
prospective data from the HUNT Study, Norway.
AB - OBJECTIVES: To prospectively investigate the association between occupational
physical activity (OPA) and disability pension due to musculoskeletal cause,
mental cause or any cause. We also examined the combined association of OPA and
leisure-time physical activity (LTPA) with disability pension. METHODS: A
population-based cohort study in Norway on 32 362 persons aged 20-65 years with
questionnaire data on OPA and LTPA that were followed up for incident disability
pension through the National Insurance Database. We used Cox regression to
estimate adjusted HRs with 95% CIs. RESULTS: During a follow-up of 9.3 years,
3837 (12%) received disability pension. Compared with people with mostly
sedentary work, those who performed much walking, much walking and lifting, and
heavy physical work had HRs of 1.26 (95% CI 1.16 to 1.38), 1.44 (95% CI 1.32 to
1.58) and 1.48 (95% CI 1.33 to 1.70), respectively. These associations were
stronger for disability pension due to musculoskeletal disorders, whereas there
was no clear association between OPA and risk of disability pension due to mental
disorders. People with high OPA and low LTPA had a HR of 1.77 (95% CI 1.58 to
1.98) for overall disability pension and HR of 2.56 (95% CI 2.10 to 3.11) for
disability pension due to musculoskeletal disorders, versus low OPA and high
LTPA. CONCLUSIONS: We observed a positive association between OPA and risk of
disability pension due to all causes and musculoskeletal disorders, but not for
mental disorders. Physical activity during leisure time reduced some, but not all
of the unfavourable effect of physically demanding work on risk of disability
pension.
PMID- 28698179
TI - A Novel Regulatory Mechanism of Smooth Muscle alpha-Actin Expression by NRG
1/circACTA2/miR-548f-5p Axis.
AB - RATIONALE: Neuregulin-1 (NRG-1) includes an extracellular epidermal growth factor
like domain and an intracellular domain (NRG-1-ICD). In response to transforming
growth factor-beta1, its cleavage by proteolytic enzymes releases a bioactive
fragment, which suppresses the vascular smooth muscle cell (VSMC) proliferation
by activating ErbB (erythroblastic leukemia viral oncogene homolog) receptor.
However, NRG-1-ICD function in VSMCs remains unknown. OBJECTIVE: Here, we
characterize the function of NRG-1-ICD and underlying mechanisms in VSMCs.
METHODS AND RESULTS: Immunofluorescence staining, Western blotting, and
quantitative real-time polymerase chain reaction showed that NRG-1 was expressed
in rat, mouse, and human VSMCs and was upregulated and cleaved in response to
transforming growth factor-beta1. In the cytoplasm of HASMCs (human aortic smooth
muscle cells), the NRG-1-ICD participated in filamentous actin formation by
interacting with alpha-SMA (smooth muscle alpha-actin). In the nucleus, the Nrg-1
ICD induced circular ACTA2 (alpha-actin-2; circACTA2) formation by recruitment of
the zinc-finger transcription factor IKZF1 (IKAROS family zinc finger 1) to the
first intron of alpha-SMA gene. We further confirmed that circACTA2, acting as a
sponge binding microRNA (miR)-548f-5p, interacted with miR-548f-5p targeting 3'
untranslated region of alpha-SMA mRNA, which in turn relieves miR-548f-5p
repression of the alpha-SMA expression and thus upregulates alpha-SMA expression,
thereby facilitating stress fiber formation and cell contraction in HASMCs.
Accordingly, in vivo studies demonstrated that the localization of the
interaction of circACTA2 with miR-548f-5p is significantly decreased in human
intimal hyperplastic arteries compared with normal arteries, implicating that
dysregulation of circACTA2 and miR-548f-5p expression is involved in intimal
hyperplasia. CONCLUSIONS: These results suggest that circACTA2 mediates NRG-1-ICD
regulation of alpha-SMA expression in HASMCs via the NRG-1-ICD/circACTA2/miR-548f
5p axis. Our data provide a molecular basis for fine-tuning alpha-SMA expression
and VSMC contraction by transcription factor, circular RNA, and microRNA.
PMID- 28698180
TI - German doctors condemn internet TV series depicting teenage suicide.
PMID- 28698181
TI - Risk factors for surgical site infection following cesarean delivery: a
retrospective cohort study.
AB - BACKGROUND: The rate of cesarean delivery is increasing in North America.
Surgical site infection following this operation can make it difficult to
recover, care for a baby and return home. We aimed to determine the incidence of
surgical site infection to 30 days following cesarean delivery, associated risk
factors and whether risk factors differed for predischarge versus postdischarge
infection. METHODS: We identified a retrospective cohort in Nova Scotia by
linking the provincial perinatal database to hospital admissions and physician
billings databases to follow women for 30 days after they had given birth by
cesarean delivery between Jan. 1, 1997 and Dec. 31, 2012. Logistic regression
with generalized estimating equations was used to determine risk factors for
infection. RESULTS: A total of 25 123 women had 33 991 cesarean deliveries over
the study period. Of the 25 123, 923 had surgical site infections, giving an
incidence rate of 2.7% (95% CI 2.54%-2.89%); the incidence decreased over time.
Risk factors for infection (adjusted odds ratios >= 1.5) were prepregnancy weight
87.0 kg or more, gaining 30.0 kg or more during pregnancy, chorioamnionitis,
maternal blood transfusion, anticoagulation therapy, alcohol or drug abuse,
second stage of labour before surgery, delivery in 1997-2000 and delivery in a
hospital performing 130-1249 cesarean deliveries annually. Women who gave birth
earlier in the study period, those who gave birth in a hospital with 130-949
cesarean deliveries per year and those with more than 1 fetus were at a
significantly higher risk for surgical site infection before discharge; women who
smoked were at significantly higher risk for surgical site infection after
discharge. INTERPRETATION: Most risk factors are known before delivery, and some
are potentially modifiable. Although the incidence of surgical site infection
decreased over time, targeted clinical and infection prevention and control
interventions could further reduce the burden of illness associated with this
health-care-related infection.
PMID- 28698182
TI - Erratum: Eular/ERA-EDTA recommendations for the management of ANCA-associated
vasculitis.
PMID- 28698184
TI - The Association of Mammographic Density and Molecular Breast Cancer Subtype.
AB - Background: Mammographic density (MD) is associated with increased breast cancer
risk, yet limited data exist on an association between MD and breast cancer
molecular subtypes.Methods: Women ages 18 years and older with breast cancer and
available mammograms between 2003 and 2012 were enrolled in a larger study on MD.
MD was classified by the Breast Imaging Reporting and Data System (BI-RADS)
classification and by volumetric breast percent density (Volpara Solutions).
Subtype was assigned by hormone receptor status, tumor grade, and mitotic score
(MS). Subtypes included: Luminal-A (ER/PR+ and grade = 1; ER/PR+ and grade = 2
and MS = 1; ER+/PR- and grade = 1; n = 233); Luminal-B (ER+ and grade = 3 or MS =
3; ER+/PR- and grade = 2; ER/PR+ and grade = 2 and MS = 2; n = 79); Her-2-neu+
(H2P; n = 59); triple-negative (ER/PR-, Her-2-; n = 86). Precancer factors
including age, race, body mass index (kg/m2), family history of breast cancer,
and history of lobular carcinoma in situ were analyzed.Results: A total of 604
patients had invasive cancer; 457 had sufficient information for analysis. Women
with H2P tumors were younger (P = 0.011) and had the highest volumetric percent
density (P = 0.002) among subgroups. Multinomial logistic regression (LA =
reference) demonstrated that although quantitative MD does not significantly
differentiate between all subtypes (P = 0.123), the association between MD and
H2P tumors is significant (OR = 1.06; confidence interval, 1.01-1.12). This
association was not seen using BI-RADS classification in bivariable analysis but
was statistically significant (P = 0.047) when controlling for other precancer
factors.Conclusions: Increased MD is more strongly associated with H2P tumors
when compared with LA.Impact: Delineating risk factors specific to breast cancer
subtype may promote development of individualized risk prediction models and
screening strategies. Cancer Epidemiol Biomarkers Prev; 26(10); 1487-92. (c)2017
AACR.
PMID- 28698185
TI - Age at Menarche and Late Adolescent Adiposity Associated with Mammographic
Density on Processed Digital Mammograms in 24,840 Women.
AB - Background: High mammographic density is strongly associated with increased
breast cancer risk. Some, but not all, risk factors for breast cancer are also
associated with higher mammographic density.Methods: The study cohort (N =
24,840) was drawn from the Research Program in Genes, Environment and Health of
Kaiser Permanente Northern California and included non-Hispanic white females
ages 40 to 74 years with a full-field digital mammogram (FFDM). Percent density
(PD) and dense area (DA) were measured by a radiological technologist using
Cumulus. The association of age at menarche and late adolescent body mass index
(BMI) with PD and DA were modeled using linear regression adjusted for
confounders.Results: Age at menarche and late adolescent BMI were negatively
correlated. Age at menarche was positively associated with PD (P value for trend
<0.0001) and DA (P value for trend <0.0001) in fully adjusted models. Compared
with the reference category of ages 12 to 13 years at menarche, menarche at age
>16 years was associated with an increase in PD of 1.47% (95% CI, 0.69-2.25) and
an increase in DA of 1.59 cm2 (95% CI, 0.48-2.70). Late adolescent BMI was
inversely associated with PD (P < 0.0001) and DA (P < 0.0001) in fully adjusted
models.Conclusions: Age at menarche and late adolescent BMI are both associated
with Cumulus measures of mammographic density on processed FFDM images.Impact:
Age at menarche and late adolescent BMI may act through different pathways. The
long-term effects of age at menarche on cancer risk may be mediated through
factors besides mammographic density. Cancer Epidemiol Biomarkers Prev; 26(9);
1450-8. (c)2017 AACR.
PMID- 28698186
TI - Serum Insulin, Glucose, Indices of Insulin Resistance, and Risk of Lung Cancer.
AB - Background: Although insulin may increase the risk of some cancers, few studies
have examined fasting serum insulin and lung cancer risk.Methods: We examined
serum insulin, glucose, and indices of insulin resistance [insulin:glucose molar
ratio and homeostasis model assessment of insulin resistance (HOMA-IR)] and lung
cancer risk using a case-cohort study within the Alpha-Tocopherol, Beta-Carotene
Cancer Prevention Study of Finnish men. A total of 196 cases and 395 subcohort
members were included. Insulin and glucose were measured in fasting serum
collected 5 to 12 years before diagnosis. Cox proportional hazards models were
utilized to estimate the relative risk of lung cancer.Results: The average time
between blood collection and lung cancer was 9.6 years. Fasting serum insulin
levels were 8.7% higher in subcohort members than cases. After multivariable
adjustment, men in the fourth quartile of insulin had a significantly higher risk
of lung cancer than those in the first quartile [HR = 2.10; 95% confidence
interval (CI), 1.12-3.94]. A similar relationship was seen with HOMA-IR (HR =
1.83; 95% CI, 0.99-3.38). Risk was not strongly associated with glucose or the
insulin:glucose molar ratio (Ptrend = 0.55 and Ptrend = 0.27,
respectively).Conclusions: Higher fasting serum insulin concentrations, as well
as the presence of insulin resistance, appear to be associated with an elevated
risk of lung cancer development.Impact: Although insulin is hypothesized to
increase risk of some cancers, insulin and lung cancer remain understudied.
Higher insulin levels and insulin resistance were associated with increased lung
cancer risk. Although smoking cessation is the best method of lung cancer
prevention, other lifestyle changes that affect insulin concentrations and
sensitivity may reduce lung cancer risk. Cancer Epidemiol Biomarkers Prev;
26(10); 1519-24. (c)2017 AACR.
PMID- 28698187
TI - The (alpha4)3(beta2)2 Stoichiometry of the Nicotinic Acetylcholine Receptor
Predominates in the Rat Motor Cortex.
AB - The alpha4beta2 nicotinic acetylcholine receptor (nAChR) is important in central
nervous system physiology and in mediating several of the pharmacological effects
of nicotine on cognition, attention, and affective states. It is also the likely
receptor that mediates nicotine addiction. This receptor assembles in two
distinct stoichiometries: (alpha4)2(beta2)3 and (alpha4)3(beta2)2, which are
referred to as high-sensitivity (HS) and low-sensitivity (LS) nAChRs,
respectively, based on a difference in the potency of acetylcholine to activate
them. The physiologic and pharmacological differences between these two receptor
subtypes have been described in heterologous expression systems. However, the
presence of each stoichiometry in native tissue currently remains unknown. In
this study, different ratios of rat alpha4 and beta2 subunit cDNA were
transfected into human embryonic kidney 293 cells to create a novel model system
of HS and LS alpha4beta2 nAChRs expressed in a mammalian cell line. The HS and LS
nAChRs were characterized through pharmacological and biochemical methods.
Isolation of surface proteins revealed higher amounts of alpha4 or beta2 subunits
in the LS or HS nAChR populations, respectively. In addition, sazetidine-A
displayed different efficacies in activating these two receptor stoichiometries.
Using this model system, a neurophysiological "two-concentration" acetylcholine
or carbachol paradigm was developed and validated to determine alpha4/beta2
subunit stoichiometry. This paradigm was then used in layers I-IV of slices of
the rat motor cortex to determine the percent contribution of HS and LS
alpha4beta2 receptors in this brain region. We report that the majority of
alpha4beta2 nAChRs in this brain region possess a stoichiometry of the
(alpha4)3(beta2)2 LS subtype.
PMID- 28698188
TI - A DAB2IP genotype: sex interaction is associated with abdominal aortic aneurysm
expansion.
AB - A faster expansion rate of abdominal aortic aneurysm (AAA) increases the risk of
rupture. Women are at higher risk of rupture than men, but the mechanisms
underlying this increased risk are unknown. We investigated whether genetic
variants that influence susceptibility for AAA (CDKN2A-2B, SORT1, DAB2IP, LRP1
and LDLR) are associated with AAA expansion and whether these associations differ
by sex in 650 patients with AAA (mean age 70+/-8 years, 17% women) enrolled in
the Mayo Clinic Vascular Disease Biorepository. Women had a mean aneurysm
expansion 0.41 mm/year greater than men after adjustment for baseline AAA size.
In addition to baseline size, mean arterial pressure (MAP), non-diabetic status,
SORT1-rs599839[G] and DAB2IP-rs7025486[A] were associated with greater aneurysm
expansion (all p<0.05). The associations of MAP and rs599839[G] were similar in
both sexes, while the associations of baseline size, pulse pressure (PP) and
rs7025486[A] were stronger in women than men (all p-sex interaction <=0.02). A
three-way interaction of PP*sex* rs7025486[A] was noted in a full-factorial
analysis (p=0.007) independent of baseline size and MAP. In the high PP group
(>=median), women had a mean growth rate 0.68 mm/year greater per [A] of
rs7025486 than men (p-sex interaction =0.003), whereas there was no difference in
the low PP group (p-sex interaction =0.8). We demonstrate that variants DAB2IP
rs7025486[A] and SORT1-rs599839[G] are associated with AAA expansion. The
association of rs7025486[A] is stronger in women than men and amplified by high
PP, contributing to sex differences in aneurysm expansion.
PMID- 28698189
TI - A comprehensive review on MEN2B.
AB - MEN2B is a very rare autosomal dominant hereditary tumor syndrome associated with
medullary thyroid carcinoma (MTC) in 100% cases, pheochromocytoma in 50% cases
and multiple extra-endocrine features, many of which can be quite disabling. Only
few data are available in the literature. The aim of this review is to try to
give further insights into the natural history of the disease and to point out
the missing evidence that would help clinicians optimize the management of such
patients. MEN2B is mainly characterized by the early occurrence of MTC, which led
the American Thyroid Association to recommend preventive thyroidectomy before the
age of 1 year. However, as the majority of mutations are de novo, improved
knowledge of the nonendocrine signs would help to lower the age of diagnosis and
improve long-term outcomes. Future large-scale studies will be aimed at
characterizing more in detail the main characteristics and outcomes of MEN2B.
PMID- 28698190
TI - Predicted Atherosclerotic Cardiovascular Disease Risk and Masked Hypertension
Among Blacks in the Jackson Heart Study.
AB - BACKGROUND: Among individuals without hypertension based on clinic blood pressure
(BP), it is unclear who should be screened for masked hypertension, defined as
having hypertension based on out-of-clinic BP. We hypothesized that individuals
with a higher 10-year predicted atherosclerotic cardiovascular disease (ASCVD)
risk, calculated using the pooled cohort risk equations, have a higher prevalence
of masked hypertension. METHODS AND RESULTS: We analyzed data from the Jackson
Heart Study-a population-based cohort of blacks-to determine the association of
predicted ASCVD risk with masked hypertension. The sample included 644
participants, 40 to 79 years of age, with clinic systolic/diastolic BP <140/90 mm
Hg, who completed ambulatory BP monitoring, were free of cardiovascular disease,
and had data on factors needed to calculate ASCVD risk. Ten-year predicted ASCVD
risk was calculated using the pooled cohort risk equations. Any masked
hypertension was defined as masked daytime hypertension (mean daytime
systolic/diastolic BP >=135/85 mm Hg), masked nighttime hypertension (mean
nighttime systolic/diastolic BP >=120/70 mm Hg), or masked 24-hour hypertension
(mean 24-hour systolic/diastolic BP >=130/80 mm Hg). The prevalence of any masked
hypertension was 54.0%. Compared with participants in the lowest (<5%) predicted
ASCVD risk category, multivariable-adjusted prevalence ratios (95% confidence
interval) for any masked hypertension were 1.36 (1.03-1.79), 1.62 (1.22-2.16),
and 1.91 (1.47-2.48) for those with ASCVD risk of 5% to <7.5%, 7.5% to <10%, and
>=10%, respectively. The C statistic for discriminating between participants with
versus without any masked hypertension was 0.681 (95% confidence interval, 0.640
0.723) for ASCVD risk and 0.703 (95% confidence interval, 0.663-0.744) for clinic
systolic BP and diastolic BP. CONCLUSIONS: Higher ASCVD risk was associated with
an increased prevalence of masked hypertension. Although the discrimination of
ASCVD risk for masked hypertension was not superior to clinic BP, risk prediction
equations may be useful for identifying the subgroup of individuals with both
masked hypertension and high predicted ASCVD risk.
PMID- 28698191
TI - Manual Versus Semiautomatic Rhythm Analysis and Defibrillation for Out-of
Hospital Cardiac Arrest.
AB - BACKGROUND: Although manual and semiautomatic external defibrillation (SAED) are
commonly used in the management of out-of-hospital cardiac arrest, the optimal
strategy is not known. We hypothesized that SAED would reduce the time to first
shock and lead to higher rates of cardioversion and survival compared with a
manual strategy. METHODS AND RESULTS: Between July 2005 and June 2015, we
included adult out-of-hospital cardiac arrest of presumed cardiac pathogenesis.
On October 2012, a treatment protocol using SAED was introduced after years of
manual defibrillation. The effect of the SAED implementation on the time to first
shock, successful cardioversion, and patient outcomes was assessed using
interrupted time series regression adjusting for arrest factors and temporal
trend. Of the 14 776 cases, 10 224 (69.2%) and 4552 (30.8%) occurred during the
manual and SAED protocols, respectively. Although the proportion of patients
shocked within 2 minutes of arrival increased during the SAED protocol for
initial shockable rhythms (from 58.9% to 69.2%; P<0.001), there was no difference
in unadjusted rate of successful cardioversion after first shock (from 12.3% to
13.8%; P=0.13). After adjustment, the odds of delivering the first shock within 2
minutes of arrival increased under the SAED protocol (adjusted odds ratio [AOR],
1.72; 95% confidence interval [CI], 1.32-2.26; P<0.001). Despite this, the SAED
protocol was associated with a reduction in survival to hospital discharge (AOR,
0.71; 95% CI, 0.55-0.92; P=0.009), event survival (AOR, 0.74; 95% CI, 0.62-0.88;
P=0.001), and prehospital return of spontaneous circulation (AOR, 0.81; 95% CI,
0.68-0.96; P=0.01) when compared with the manual protocol. There was also no
improvement in the rate of successful cardioversion after first shock (AOR, 0.73;
95% CI, 0.51-1.06; P=0.10). CONCLUSIONS: Although SAED improved the time to first
shock, this did not translate into higher rates of successful cardioversion or
survival after out-of-hospital cardiac arrest. Advanced life support providers
should be trained to use a manual defibrillation protocol.
PMID- 28698192
TI - Twenty-Year Nationwide Trends in Statin Utilization and Expenditure in Denmark.
PMID- 28698193
TI - Masked Hypertension: Finding Trouble Under the Disguise.
PMID- 28698194
TI - Love?
PMID- 28698195
TI - An unpredictable vision.
PMID- 28698196
TI - Congenital Glaucoma.
PMID- 28698197
TI - Clinical academic workforce continues to shrink.
PMID- 28698198
TI - ABCB1 Mediates Cabazitaxel-Docetaxel Cross-Resistance in Advanced Prostate
Cancer.
AB - Advancements in research have added several new therapies for castration
resistant prostate cancer (CRPC), greatly augmenting our ability to treat
patients. However, CRPC remains an incurable disease due to the development of
therapeutic resistance and the existence of cross-resistance between available
therapies. Understanding the interplay between different treatments will lead to
improved sequencing and the creation of combinations that overcome resistance and
prolong survival. Whether there exists cross-resistance between docetaxel and the
next-generation taxane cabazitaxel is poorly understood. In this study, we use C4
2B and DU145 derived docetaxel-resistant cell lines to test response to
cabazitaxel. Our results demonstrate that docetaxel resistance confers cross
resistance to cabazitaxel. We show that increased ABCB1 expression is responsible
for cross-resistance to cabazitaxel and that inhibition of ABCB1 function through
the small-molecule inhibitor elacridar resensitizes taxane-resistant cells to
treatment. In addition, the antiandrogens bicalutamide and enzalutamide,
previously demonstrated to be able to resensitize taxane-resistant cells to
docetaxel through inhibition of ABCB1 ATPase activity, are also able to
resensitize resistant cells to cabazitaxel treatment. Finally, we show that
resensitization using an antiandrogen is far more effective in combination with
cabazitaxel than docetaxel. Collectively, these results address key concerns in
the field, including that of cross-resistance between taxanes and highlighting a
mechanism of cabazitaxel resistance involving ABCB1. Furthermore, these
preclinical studies suggest the potential in using combinations of antiandrogens
with cabazitaxel for increased effect in treating advanced CRPC. Mol Cancer Ther;
16(10); 2257-66. (c)2017 AACR.
PMID- 28698199
TI - MiR-125b Increases Nasopharyngeal Carcinoma Radioresistance by Targeting A20/NF
kappaB Signaling Pathway.
AB - Radioresistance poses a major challenge in nasopharyngeal carcinoma (NPC)
treatment, but little is known about how miRNA regulates this phenomenon. In this
study, we investigated the function and mechanism of miR-125b in NPC
radioresistance, one of upregulated miRNAs in the radioresistant NPC cells
identified by our previous microarray analysis. We observed that miR-125b was
frequently upregulated in the radioresistant NPCs, and its increment was
significantly correlated with NPC radioresistance, and was an independent
predictor for poor patient survival. In vitro radioresponse assays showed that
miR-125b inhibitor decreased, whereas miR-125b mimic increased NPC cell
radioresistance. In a mouse model, therapeutic administration of miR-125b
antagomir dramatically sensitized NPC xenografts to irradiation. Mechanistically,
we confirmed that A20 was a direct target of miR-125b and found that miR-125b
regulated NPC cell radioresponse by targeting A20/NF-kappaB signaling. With a
combination of loss-of-function and gain-of-function approaches, we further
showed that A20 overexpression decreased while A20 knockdown increased NPC cell
radioresistance both in vitro and in vivo Moreover, A20 was significantly
downregulated while p-p65 (RelA) significantly upregulated in the radioresistant
NPCs relative to radiosensitive NPCs, and miR-125b expression level was
negatively associated with A20 expression level, whereas positively associated
with p-p65 (RelA) level. Our data demonstrate that miR-125b and A20 are critical
regulators of NPC radioresponse, and high miR-125b expression enhances NPC
radioresistance through targeting A20 and then activating the NF-kappaB signaling
pathway, highlighting the therapeutic potential of the miR-125b/A20/NF-kappaB
axis in clinical NPC radiosensitization. Mol Cancer Ther; 16(10); 2094-106.
(c)2017 AACR.
PMID- 28698200
TI - Targeting AXL and mTOR Pathway Overcomes Primary and Acquired Resistance to WEE1
Inhibition in Small-Cell Lung Cancer.
AB - Purpose: Drugs targeting DNA repair and cell-cycle checkpoints have emerged as
promising therapies for small-cell lung cancer (SCLC). Among these, the WEE1
inhibitor AZD1775 has shown clinical activity in a subset of SCLC patients, but
resistance is common. Understanding primary and acquired resistance mechanisms
will be critical for developing effective WEE1 inhibitor
combinations.Experimental Design: AZD1775 sensitivity in SCLC cell lines was
correlated with baseline expression level of 200 total or phosphorylated proteins
measured by reverse-phase protein array (RPPA) to identify predictive markers of
primary resistance. We further established AZD1775 acquired resistance models to
identify mechanism of acquired resistance. Combination regimens were tested to
overcome primary and acquired resistance to AZD1775 in in vitro and in vivo SCLC
models.Results: High-throughput proteomic profiling demonstrate that SCLC models
with primary resistance to AZD1775 express high levels of AXL and phosphorylated
S6 and that WEE1/AXL or WEE1/mTOR inhibitor combinations overcome resistance in
vitro and in vivo Furthermore, AXL, independently and via mTOR, activates the ERK
pathway, leading to recruitment and activation of another G2-checkpoint protein,
CHK1. AZD1775 acquired resistance models demonstrated upregulation of AXL, pS6,
and MET, and resistance was overcome with the addition of AXL (TP0903), dual
AXL/MET (cabozantinib), or mTOR (RAD001) inhibitors.Conclusions: AXL promotes
resistance to WEE1 inhibition via downstream mTOR signaling and resulting
activation of a parallel DNA damage repair pathway, CHK1. These findings suggest
rational combinations to enhance the clinical efficacy of AZD1775, which is
currently in clinical trials for SCLC and other malignancies. Clin Cancer Res;
23(20); 6239-53. (c)2017 AACR.
PMID- 28698201
TI - Entinostat Neutralizes Myeloid-Derived Suppressor Cells and Enhances the
Antitumor Effect of PD-1 Inhibition in Murine Models of Lung and Renal Cell
Carcinoma.
AB - PURPOSE: Recent advances in immunotherapy highlight the antitumor effects of
immune checkpoint inhibition despite a relatively limited subset of patients
receiving clinical benefit. The selective class I histone deacetylase inhibitor
entinostat has been reported to have immunomodulatory activity including
targeting of immune suppressor cells in the tumor microenvironment. Thus, we
decided to assess whether entinostat could enhance anti-PD-1 treatment and
investigate those alterations in the immunosuppressive tumor microenvironment
that contribute to the combined antitumor activity. EXPERIMENTAL DESIGN: We
utilized syngeneic mouse models of lung (LLC) and renal cell (RENCA) carcinoma
and assessed immune correlates, tumor growth, and survival following treatment
with entinostat (5 or 10 mg/kg, p.o.) and a PD-1 inhibitor (10 and 20 mg/kg,
s.c.). RESULTS: Entinostat enhanced the antitumor effect of PD-1 inhibition in
two syngeneic mouse tumor models by reducing tumor growth and increasing
survival. Entinostat inhibited the immunosuppressive function of both
polymorphonuclear (PMN)- and monocytic-myeloid derived suppressor cell (M-MDSC)
populations. Analysis of MDSC response to entinostat revealed significantly
reduced arginase-1, iNOS, and COX-2 levels, suggesting potential mechanisms for
the altered function. We also observed significant alterations in
cytokine/chemokine release in vivo with a shift toward a tumor-suppressive
microenvironment. CONCLUSIONS: Our results demonstrate that entinostat enhances
the antitumor effect of PD-1 targeting through functional inhibition of MDSCs and
a transition away from an immune-suppressive tumor microenvironment. These data
provide a mechanistic rationale for the clinical testing and potential markers of
response of this novel combination in solid tumor patients.
PMID- 28698202
TI - Sorafenib in Patients with Hepatocellular Carcinoma-Results of the Observational
INSIGHT Study.
AB - Purpose: Sorafenib is the only currently approved systemic therapy for advanced
hepatocellular carcinoma (HCC). We aimed to evaluate the safety and efficacy of
sorafenib therapy in patients with HCC under real-life conditions regarding
patient, tumor characteristics, and any adverse events at study entry and at
follow-up visits every 2 to 4 months.Experimental Design: The current INSIGHT
study is a noninterventional, prospective, multicenter, observational study
performed in 124 sites across Austria and Germany between 2008 and 2014.Results:
Median overall survival and time to progression (RECIST) were found to be
dependent on baseline Barcelona Clinic Liver Cancer (BCLC) tumor stage (A: 29.2,
B: 19.6, C: 13.6, D: 3.1 and A: 6.0, B: 5.5, C: 3.9, and D: 1.7 months,
respectively), Child-Pugh liver function (A: 17.6, B: 8.1, C: 5.6 and A: 5.3, B:
3.3, C: 2.5 months, respectively), and performance status of the patient;
however, age did not affect prognosis. Sorafenib-related adverse events at any
grade occurred in 64.9% of patients, with diarrhea (35.4%), hand-foot-skin
reaction (16.6%), nausea (10.3%), and fatigue (11.2%) occurring most
frequently.Conclusions: Sorafenib treatment was shown to be effective in a real
life setting, in agreement with previously reported clinical trial data. The
therapy was found to have an acceptable safety profile, with predominantly mild
to moderate side effects. Clin Cancer Res; 23(19); 5720-8. (c)2017 AACR.
PMID- 28698203
TI - Posttransplant feasibility study of nilotinib prophylaxis for high-risk
Philadelphia chromosome positive leukemia.
PMID- 28698204
TI - Hematologic relapse in AL amyloidosis after high-dose melphalan and stem cell
transplantation.
PMID- 28698205
TI - An Fc-engineered CD19 antibody eradicates MRD in patient-derived MLL-rearranged
acute lymphoblastic leukemia xenografts.
AB - Antibody therapy constitutes a major advance in the treatment of B-cell precursor
acute lymphoblastic leukemia (BCP-ALL). To evaluate the efficacy and the
mechanisms of action of CD19 monoclonal antibody therapy in pediatric BCP-ALL, we
tested an Fc-engineered CD19 antibody carrying the S239D/I332E mutation for
improved effector cell recruitment (CD19-DE). Patient-derived xenografts (PDX) of
pediatric mixed-lineage leukemia gene (MLL)-rearranged ALL were established in
NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ (NSG) mice. Antibody CD19-DE was efficient in
prolonging the survival of NSG mice in a minimal residual disease (MRD) model.
The majority of surviving mice remained polymerase chain reaction (PCR)-MRD
negative after treatment. When antibody therapy was initiated in overt leukemia,
antibody CD19-DE was still efficient in prolonging survival of xenografted mice
in comparison with nontreated control animals, but the effects were less
pronounced than in the MRD setting. Importantly, the combination of antibody CD19
DE and cytoreduction by chemotherapy (dexamethasone, vincristine, PEG
asparaginase) resulted in significantly improved survival rates in xenografted
mice. Antibody CD19-DE treatment was also efficient in a randomized phase 2-like
PDX trial using 13 MLL-rearranged BCP-ALL samples. Macrophage depletion by
liposomal clodronate resulted in a reversal of the beneficial effects of CD19-DE,
suggesting an important role for macrophages as effector cells. In support of
this finding, CD19-DE was found to enhance phagocytosis of patient-derived ALL
blasts by human macrophages in vitro. Thus, Fc-engineered CD19 antibodies may
represent a promising treatment option for infants and children with MLL
rearranged BCP-ALL who have a poor outcome when treated with chemotherapy only.
PMID- 28698206
TI - Expression of PIM kinases in Reed-Sternberg cells fosters immune privilege and
tumor cell survival in Hodgkin lymphoma.
AB - Reed-Sternberg (RS) cells of classical Hodgkin lymphoma (cHL) express multiple
immunoregulatory proteins that shape the cHL microenvironment and allow tumor
cells to evade immune surveillance. Expression of certain immunoregulatory
proteins is modulated by prosurvival transcription factors, such as NFkappaB and
STATs. Because these factors also induce expression of the oncogenic PIM1/2/3
serine/threonine kinases, and as PIMs modulate transcriptional activity of
NFkappaB and STATs, we hypothesized that these kinases support RS cell survival
and foster their immune privilege. Here, we investigated PIM1/2/3 expression in
cHL and assessed their role in developing RS cell immune privilege and survival.
PIM1/2/3 were ubiquitously expressed in primary and cultured RS cells, and their
expression was driven by JAK-STAT and NFkappaB activity. Genetic or chemical PIM
inhibition with a newly developed pan-PIM inhibitor, SEL24-B489, induced RS cell
apoptosis. PIM inhibition decreased cap-dependent protein translation, blocked
JAK-STAT signaling, and markedly attenuated NFkappaB-dependent gene expression.
In a cHL xenograft model, SEL24-B489 delayed tumor growth by 95.8% (P = .0002).
Furthermore, SEL24-B489 decreased the expression of multiple molecules engaged in
developing the immunosuppressive microenvironment, including galectin-1 and PD
L1/2. In coculture experiments, T cells incubated with SEL24-B489-treated RS
cells exhibited higher expression of activation markers than T cells coincubated
with control RS cells. Taken together, our data indicate that PIM kinases in cHL
exhibit pleiotropic effects, orchestrating tumor immune escape and supporting RS
cell survival. Inhibition of PIM kinases decreases RS cell viability and disrupts
signaling circuits that link these cells with their niches. Thus, PIM kinases are
promising therapeutic targets in cHL.
PMID- 28698207
TI - Strict tropism for CD71+/CD234+ human reticulocytes limits the zoonotic potential
of Plasmodium cynomolgi.
AB - Two malaria parasites of Southeast Asian macaques, Plasmodium knowlesi and P
cynomolgi, can infect humans experimentally. In Malaysia, where both species are
common, zoonotic knowlesi malaria has recently become dominant, and cases are
recorded throughout the region. By contrast, to date, only a single case of
naturally acquired P cynomolgi has been found in humans. In this study, we show
that whereas P cynomolgi merozoites invade monkey red blood cells
indiscriminately in vitro, in humans, they are restricted to reticulocytes
expressing both transferrin receptor 1 (Trf1 or CD71) and the Duffy
antigen/chemokine receptor (DARC or CD234). This likely contributes to the
paucity of detectable zoonotic cynomolgi malaria. We further describe
postinvasion morphologic and rheologic alterations in P cynomolgi-infected human
reticulocytes that are strikingly similar to those observed for P vivax These
observations stress the value of P cynomolgi as a model in the development of
blood stage vaccines against vivax malaria.
PMID- 28698208
TI - Plasma lipoprotein subfraction concentrations are associated with lipid
metabolism and age-related macular degeneration.
AB - Disturbance in lipid metabolism has been suggested as a major pathogenic factor
for age-related macular degeneration (AMD). Conventional lipid measures have been
inconsistently associated with AMD. Other factors that can alter lipid metabolism
include lipoprotein phenotype and genetic mutations. We performed a case-control
study to examine the association between lipoprotein profile and neovascular AMD
(nAMD) and whether the cholesterylester transfer protein (CETP) D442G mutation
modulates these associations. Patients with nAMD had significantly higher
concentrations of HDL and IDL compared with controls. The increase in HDL
particles in nAMD patients was driven by an excess of medium-sized particles.
Concurrently, patients with nAMD also had lower Apo A-1, lower VLDL and
chylomicron lipoprotein. Many of these associations showed a dose-dependent
association between controls, early AMD cases, and nAMD cases. Adjustment for the
presence of the D442G mutation at the CETP locus did not significantly alter the
increased AMD risk associated with HDL particle concentration. AMD is associated
with variation in many lipoprotein subclasses, including increased HDL and IDL
particles and decreased Apo A-1, VLDL, and chylomicron particles. These data
suggest widespread systemic disturbance in lipid metabolism in the pathogenesis
of AMD, including possible alterations in lipoprotein carrier capacity.
PMID- 28698209
TI - Lipoprotein(a): the common, likely causal, yet elusive risk factor for
cardiovascular disease.
PMID- 28698210
TI - APOBEC3A and APOBEC3B Activities Render Cancer Cells Susceptible to ATR
Inhibition.
AB - The apolipoprotein B mRNA editing enzyme catalytic polypeptide-like APOBEC3A and
APOBEC3B have emerged as key mutation drivers in cancer. Here, we show that
APOBEC3A and APOBEC3B activities impose a unique type of replication stress by
inducing abasic sites at replication forks. In contrast to cells under other
types of replication stress, APOBEC3A-expressing cells were selectively sensitive
to ATR inhibitors (ATRi), but not to a variety of DNA replication inhibitors and
DNA-damaging drugs. In proliferating cells, APOBEC3A modestly elicited ATR but
not ATM. ATR inhibition in APOBEC3A-expressing cells resulted in a surge of
abasic sites at replication forks, revealing an ATR-mediated negative feedback
loop during replication. The surge of abasic sites upon ATR inhibition associated
with increased accumulation of single-stranded DNA, a substrate of APOBEC3A,
triggering an APOBEC3A-driven feed-forward loop that ultimately drove cells into
replication catastrophe. In a panel of cancer cell lines, ATRi selectively
induced replication catastrophe in those harboring high APOBEC3A and/or APOBEC3B
activities, showing that APOBEC3A and APOBEC3B activities conferred
susceptibility to ATRi. Our results define an APOBEC-driven replication stress in
cancer cells that may offer an opportunity for ATR-targeted therapy. Cancer Res;
77(17); 4567-78. (c)2017 AACR.
PMID- 28698211
TI - Extra-rectal lymphogranuloma venereum in France: a clinical and molecular study.
AB - OBJECTIVES: To describe a series of extrarectal lymphogranuloma venereum (LGV)
cases diagnosed in France. METHODS: Consecutive LGV cases confirmed at the French
Reference Centre for chlamydiae with an extrarectal sample from January 2010 to
December 2015 were included. The first part of the study consisted of a
retrospective case note review and analysis. In a second part, the complete ompA
gene sequence of our samples was determined. RESULTS: There were 56 cases
overall: 50 cases of genital LGV and six cases of pharyngeal LGV. Subjects were
all men, median age 39 years, 27/53 were HIV-positive, 47/51 reported having sex
with other men, 43/49 reported multiple sexual partners (a mean 25 in the last 6
months). Median time from symptom onset to diagnosis was 21 days. Subjects most
commonly presented with inguinal adenopathy alone (19 of 50 genital cases) and
adenopathy with genital ulcer (17 of 50). Three pharyngeal cases were
symptomatic. Fever was reported in 11 cases. Inguinal abscess was reported in 22
of 42 cases presenting with lymphadenopathy. Co-infections were frequent: eight
cases of syphilis, four non-LGV Chlamydia trachomatis infections, one case of
gonorrhoea. Cure was always achieved with doxycycline therapy but prolonged
treatment was necessary in eight cases with inguinal abscess. Genotyping
according to ompA sequencing showed the co-circulation of genovars L2 (16 of 42
strains successfully typed) and L2b (24 of 42). There was no association between
HIV status and disease severity or genovar distribution. CONCLUSION: In the span
of 6 years, 56 extrarectal LGV cases were confirmed through genotyping in France.
Extrarectal LGV seemed to share a common epidemiological background with rectal
disease in terms of affected population and genovar distribution. HIV prevalence
was lower than expected.
PMID- 28698212
TI - Erratum for the Research Article: "Agrobacterium Counteracts Host-Induced
Degradation of Its Effector F-Box Protein" by S. Magori and V. Citovsky.
PMID- 28698213
TI - Gene expression profiles of brain endothelial cells during embryonic development
at bulk and single-cell levels.
AB - The blood-brain barrier is a dynamic interface that separates the brain from the
circulatory system, and it is formed by highly specialized endothelial cells. To
explore the molecular mechanisms defining the unique nature of vascular
development and differentiation in the brain, we generated high-resolution gene
expression profiles of mouse embryonic brain endothelial cells using translating
ribosome affinity purification and single-cell RNA sequencing. We compared the
brain vascular translatome with the vascular translatomes of other organs and
analyzed the vascular translatomes of the brain at different time points during
embryonic development. Because canonical Wnt signaling is implicated in the
formation of the blood-brain barrier, we also compared the brain endothelial
translatome of wild-type mice with that of mice lacking the transcriptional
cofactor beta-catenin (Ctnnb1). Our analysis revealed extensive molecular changes
during the embryonic development of the brain endothelium. We identified genes
encoding brain endothelium-specific transcription factors (Foxf2, Foxl2, Foxq1,
Lef1, Ppard, Zfp551, and Zic3) that are associated with maturation of the blood
brain barrier and act downstream of the Wnt-beta-catenin signaling pathway.
Profiling of individual brain endothelial cells revealed substantial
heterogeneity in the population. Nevertheless, the high abundance of Foxf2,
Foxq1, Ppard, or Zic3 transcripts correlated with the increased expression of
genes encoding markers of brain endothelial cell differentiation. Expression of
Foxf2 and Zic3 in human umbilical vein endothelial cells induced the production
of blood-brain barrier differentiation markers. This comprehensive data set may
help to improve the engineering of in vitro blood-brain barrier models.
PMID- 28698217
TI - New connections: Amyloid-beta, calcium, and the synapse.
AB - Insight into how amyloid-beta impairs synaptic function reveals potential
therapeutic targets for patients with Alzheimer's disease.
PMID- 28698218
TI - Heart failure inhibitor.
AB - Targeting a G protein-coupled receptor in cardiomyocytes offers protection in a
mouse model of cardiac failure.
PMID- 28698219
TI - The transcription factor C/EBPbeta in the dorsal root ganglion contributes to
peripheral nerve trauma-induced nociceptive hypersensitivity.
AB - Changes in gene transcription in the dorsal root ganglion (DRG) after nerve
trauma contribute to the genesis of neuropathic pain. We report that peripheral
nerve trauma caused by chronic constriction injury (CCI) increased the abundance
of the transcription factor C/EBPbeta (CCAAT/enhancer binding protein beta) in
the DRG. Blocking this increase mitigated the development and maintenance of CCI
induced mechanical, thermal, and cold pain hypersensitivities without affecting
basal responses to acute pain and locomotor activity. Conversely, mimicking this
increase produced hypersensitivity to mechanical, thermal, or cold pain. In the
ipsilateral DRG, C/EBPbeta promoted a decrease in the abundance of the voltage
gated potassium channel subunit Kv1.2 and MU opioid receptor (MOR) at the mRNA
and protein levels, which would be predicted to increase excitability in the
ipsilateral DRG neurons and reduce the efficacy of morphine analgesia. These
effects required C/EPBbeta-mediated transcriptional activation of Ehmt2
(euchromatic histone-lysine N-methyltransferase 2), which encodes G9a, an
epigenetic silencer of the genes encoding Kv1.2 and MOR. Blocking the increase in
C/EBPbeta in the DRG improved morphine analgesia after CCI. These results suggest
that C/EBPbeta is an endogenous initiator of neuropathic pain and could be a
potential target for the prevention and treatment of this disorder.
PMID- 28698220
TI - Activation of CaMKIV by soluble amyloid-beta1-42 impedes trafficking of axonal
vesicles and impairs activity-dependent synaptogenesis.
AB - The prefibrillar form of soluble amyloid-beta (sAbeta1-42) impairs synaptic
function and is associated with the early phase of Alzheimer's disease (AD). We
investigated how sAbeta1-42 led to presynaptic defects using a quantum dot-based,
single particle-tracking method to monitor synaptic vesicle (SV) trafficking
along axons. We found that sAbeta1-42 prevented new synapse formation induced by
chemical long-term potentiation (cLTP). In cultured rat hippocampal neurons,
nanomolar amounts of sAbeta1-42 impaired Ca2+ clearance from presynaptic
terminals and increased the basal Ca2+ concentration. This caused an increase in
the phosphorylation of Ca2+/calmodulin-dependent protein kinase IV (CaMKIV) and
its substrate synapsin, which markedly inhibited SV trafficking along axons
between synapses. Neurons derived from a transgenic AD mouse model had similar
defects, which were prevented by an inhibitor of CaMK kinase (CaMKK; which
activates CaMKIV), by antibodies against Abeta1-42, or by expression a
phosphodeficient synapsin mutant. The CaMKK inhibitor also abolished the defects
in activity-dependent synaptogenesis caused by sAbeta1-42 Our results suggest
that by disrupting SV reallocation between synapses, sAbeta1-42 prevents neurons
from forming new synapses or adjusting strength and activity among neighboring
synapses. Targeting this mechanism might prevent synaptic dysfunction in AD
patients.
PMID- 28698221
TI - Patellar and Achilles tendinopathies are predominantly peripheral pain states: a
blinded case control study of somatosensory and psychological profiles.
AB - STUDY DESIGN: Case-control design. BACKGROUND: Tendinopathy is characterised by
pain on tendon loading. In persistent cases of upper limb tendinopathy, it is
frequently associated with central nervous system sensitisation, whereas less
commonly linked in the case of persistent lower limb tendinopathies. OBJECTIVES:
Compare somatosensory and psychological profiles of participants with persistent
patellar (PT) and Achilles tendinopathies (AT) with pain-free controls. METHODS:
A comprehensive battery of Quantitative Sensory Testing (QST) was assessed at
standardised sites of the affected tendon and remotely (lateral elbow) by a
blinded assessor. Participants completed the Victorian Institute of Sports
Assessment, a health-related quality of life questionnaire, the Hospital Anxiety
and Depression Scale and the Active Australia Questionnaire. Independent t-test
and analysis of covariance (sex-adjusted and age-adjusted) were performed to
compare groups. RESULTS: Participants with PT and AT did not exhibit differences
from controls for the QST at the remote site, but there were differences at the
affected tendon site. Compared with controls, participants with PT displayed
significantly lower pressure pain threshold locally at the tendon (p=0.012) and
fewer single limb decline squats before pain onset, whereas participants with AT
only displayed fewer single heel raises before pain onset, but this pain was of a
higher intensity. CONCLUSION: PT and AT appear to be predominantly local not
widespread pain states related to loading of tendons without significant features
of central sensitisation. LEVEL OF EVIDENCE: Level 4.
PMID- 28698223
TI - GP who certified taxi drivers without examining them gets 12 month suspension.
PMID- 28698222
TI - A systematic review, meta-analysis and meta-regression of the effect of protein
supplementation on resistance training-induced gains in muscle mass and strength
in healthy adults.
AB - OBJECTIVE: We performed a systematic review, meta-analysis and meta-regression to
determine if dietary protein supplementation augments resistance exercise
training (RET)-induced gains in muscle mass and strength. DATA SOURCES: A
systematic search of Medline, Embase, CINAHL and SportDiscus. ELIGIBILITY
CRITERIA: Only randomised controlled trials with RET >=6 weeks in duration and
dietary protein supplementation. DESIGN: Random-effects meta-analyses and meta
regressions with four a priori determined covariates. Two-phase break point
analysis was used to determine the relationship between total protein intake and
changes in fat-free mass (FFM). RESULTS: Data from 49 studies with 1863
participants showed that dietary protein supplementation significantly (all
p<0.05) increased changes (means (95% CI)) in: strength-one-repetition-maximum
(2.49 kg (0.64, 4.33)), FFM (0.30 kg (0.09, 0.52)) and muscle size-muscle fibre
cross-sectional area (CSA; 310 um2 (51, 570)) and mid-femur CSA (7.2 mm2 (0.20,
14.30)) during periods of prolonged RET. The impact of protein supplementation on
gains in FFM was reduced with increasing age (-0.01 kg (-0.02,-0.00), p=0.002)
and was more effective in resistance-trained individuals (0.75 kg (0.09, 1.40),
p=0.03). Protein supplementation beyond total protein intakes of 1.62 g/kg/day
resulted in no further RET-induced gains in FFM. SUMMARY/CONCLUSION: Dietary
protein supplementation significantly enhanced changes in muscle strength and
size during prolonged RET in healthy adults. Increasing age reduces and training
experience increases the efficacy of protein supplementation during RET. With
protein supplementation, protein intakes at amounts greater than ~1.6 g/kg/day do
not further contribute RET-induced gains in FFM.
PMID- 28698224
TI - Special Meeting Sections for the 6th ASM Conference on Beneficial Microbes.
PMID- 28698227
TI - Comparative transcriptomics of hepatic differentiation of human pluripotent stem
cells and adult human liver tissue.
AB - Hepatocytes derived from human pluripotent stem cells (hPSC-HEP) have the
potential to replace presently used hepatocyte sources applied in liver disease
treatment and models of drug discovery and development. Established hepatocyte
differentiation protocols are effective and generate hepatocytes, which
recapitulate some key features of their in vivo counterparts. However, generating
mature hPSC-HEP remains a challenge. In this study, we applied transcriptomics to
investigate the progress of in vitro hepatic differentiation of hPSCs at the
developmental stages, definitive endoderm, hepatoblasts, early hPSC-HEP, and
mature hPSC-HEP, to identify functional targets that enhance efficient hepatocyte
differentiation. Using functional annotation, pathway and protein interaction
network analyses, we observed the grouping of differentially expressed genes in
specific clusters representing typical developmental stages of hepatic
differentiation. In addition, we identified hub proteins and modules that were
involved in the cell cycle process at early differentiation stages. We also
identified hub proteins that differed in expression levels between hPSC-HEP and
the liver tissue controls. Moreover, we identified a module of genes that were
expressed at higher levels in the liver tissue samples than in the hPSC-HEP.
Considering that hub proteins and modules generally are essential and have
important roles in the protein-protein interactions, further investigation of
these genes and their regulators may contribute to a better understanding of the
differentiation process. This may suggest novel target pathways and molecules for
improvement of hPSC-HEP functionality, having the potential to finally bring this
technology to a wider use.
PMID- 28698226
TI - Loss of DNA methylation in zebrafish embryos activates retrotransposons to
trigger antiviral signaling.
AB - Complex cytoplasmic nucleotide-sensing mechanisms can recognize foreign DNA based
on a lack of methylation and initiate an immune response to clear the infection.
Zebrafish embryos with global DNA hypomethylation caused by mutations in the
ubiquitin-like with PHD and ring finger domains 1 (uhrf1) or DNA
methyltransferase 1 (dnmt1) genes exhibit a robust interferon induction
characteristic of the first line of defense against viral infection. We found
that this interferon induction occurred in non-immune cells and examined whether
intracellular viral sensing pathways in these cells were the trigger. RNA-seq
analysis of uhrf1 and dnmt1 mutants revealed widespread induction of Class I
retrotransposons and activation of cytoplasmic DNA viral sensors. Attenuating
Sting, phosphorylated Tbk1 and, importantly, blocking reverse transcriptase
activity suppressed the expression of interferon genes in uhrf1 mutants. Thus,
activation of transposons in cells with global DNA hypomethylation mimics a viral
infection by activating cytoplasmic DNA sensors. This suggests that antiviral
pathways serve as surveillance of cells that have derepressed intragenomic
parasites due to DNA hypomethylation.
PMID- 28698228
TI - Perturbations to lysyl oxidase expression broadly influence the transcriptome of
lung fibroblasts.
AB - Lysyl oxidases are credited with pathogenic roles in lung diseases, including
cancer, fibrosis, pulmonary hypertension, congenital diaphragmatic hernia, and
bronchopulmonary dysplasia (BPD). Lysyl oxidases facilitate the covalent intra-
and intermolecular cross-linking of collagen and elastin fibers, thereby
imparting tensile strength to the extracellular matrix (ECM). Alternative ECM
independent roles have recently been proposed for lysyl oxidases, including
regulation of growth factor signaling, chromatin remodeling, and transcriptional
regulation, all of which impact cell phenotype. We demonstrate here that three of
the five lysyl oxidase family members, Lox, Loxl1, and Loxl2, are highly
expressed in primary mouse lung fibroblasts compared with other constituent cell
types of the lung. Microarray analyses revealed that small interfering RNA
knockdown of Lox, Loxl1, and Loxl2 was associated with apparent changes in the
expression of 134, 3,761, and 3,554 genes, respectively, in primary mouse lung
fibroblasts. The impact of lysyl oxidase expression on steady-state Mmp3, Mmp9,
Eln, Rarres1, Gdf10, Ifnb1, Csf2, and Cxcl9 mRNA levels was validated, which is
interesting, since the corresponding gene products are relevant to lung
development and BPD, where lysyl oxidases play a functional role. In vivo, the
expression of these genes broadly correlated with Lox, Loxl1, and Loxl2
expression in a mouse model of BPD. Furthermore, beta-aminopropionitrile (BAPN),
a selective lysyl oxidase inhibitor, did not affect the steady-state mRNA levels
of lysyl oxidase target genes, in vitro in lung fibroblasts or in vivo in BAPN
treated mice. This study is the first to report that lysyl oxidases broadly
influence the cell transcriptome.
PMID- 28698229
TI - Changes in the phosphoproteome of brown adipose tissue during hibernation in the
ground squirrel, Ictidomys tridecemlineatus.
AB - Mammalian hibernation is characterized by metabolic rate depression and a strong
decrease in core body temperature that together create energy savings such that
most species do not have to eat over the winter months. Brown adipose tissue
(BAT), a thermogenic tissue that uses uncoupled mitochondrial respiration to
generate heat instead of ATP, plays a major role in rewarming from deep torpor.
In the present study we developed a label-free liquid chromatography mass
spectrometry (LC-MS) strategy to investigate both differential protein expression
and protein phosphorylation in BAT extracts from euthermic vs. hibernating ground
squirrels (Ictidomys tridecemlineatus). In particular, we incorporated the filter
assisted sample preparation protocol, which provides a more in-depth analysis
compared with gel-based and other LC-MS proteomics approaches. Surprisingly,
mitochondrial membrane and matrix protein expression in BAT was largely constant
between active euthermic squirrels and their hibernating counterparts. Validation
by immunoblotting confirmed that the protein levels of mitochondrial respiratory
chain complexes were largely unchanged in hibernating vs. euthermic animals. On
the other hand, phosphoproteomics revealed that pyruvate dehydrogenase (PDH)
phosphorylation increased during squirrel hibernation, confirmed by
immunoblotting with phospho-specific antibodies. PDH phosphorylation leads to its
inactivation, which suggests that BAT carbohydrate oxidation is inhibited during
hibernation. Phosphorylation of hormone-sensitive lipase (HSL) was also found to
increase during hibernation, suggesting that HSL would be active in BAT to
produce the fatty acids that are likely the primary fuel for thermogenesis upon
arousal. Increased perilipin phosphorylation along with that of a number of other
proteins was also revealed, emphasizing the importance of protein phosphorylation
as a regulatory mechanism during mammalian hibernation.
PMID- 28698230
TI - Chromoendoscopy versus narrow band imaging in UC: a prospective randomised
controlled trial.
AB - BACKGROUND: Patients with long-standing UC have an increased risk for the
development of colonic neoplastic lesions. Chromoendoscopy (CE) has been proven
to enhance neoplasia detection while the role of virtual chromoendoscopy (VC) is
still to be defined. OBJECTIVE: To compare the performance of CE to VC for the
detection of neoplastic lesions in patients with long-standing UC. DESIGN: A
multicentre prospective randomised controlled trial. 131 patients with long
standing UC were randomised between CE with methylene blue 0.1% (n=66) or VC with
narrow band imaging (NBI) (n=65). Biopsies were taken from visible lesions and
surrounding mucosa. No random biopsies were performed. The primary outcome was
the difference in total number of neoplastic lesions detected in each group.
RESULTS: There was no significant difference between NBI and CE for neoplasia
detection. Mean number of neoplastic lesions per colonoscopy was 0.47 for CE and
0.32 for NBI (p=0.992). The neoplasia detection rate was not different between CE
(21.2%) and NBI (21.5%) (OR 1.02 (95% CI 0.44 to 2.35, p=0.964). Biopsies from
the surrounding mucosa yielded no diagnosis or dysplasia. The per lesion
neoplasia detection was 17.4% for CE and 16.3% for NBI (OR 1.09 (95% CI 0.59 to
1.99, p=0.793). The total procedural time was on average 7 min shorter in the NBI
group. CONCLUSION: CE and NBI do not differ significantly for detection of
colitis-associated neoplasia. Given the longer withdrawal time for CE and easier
applicability, NBI may possibly replace classical CE. TRIAL REGISTRATION NUMBER:
NCT01882205; Results.
PMID- 28698231
TI - Survival benefit of statin use in ankylosing spondylitis: a general population
based cohort study.
AB - OBJECTIVES: Recent studies have shown an increase in both cardiovascular and all
cause mortality in ankylosing spondylitis (AS). We examined the potential
survival benefit of statin use in AS within a general population context.
METHODS: We performed an incident user cohort study with time-stratified
propensity score matching using a UK general population database between 1
January 2000 and 31 December 2014. To account for potential confounders, we
compared propensity score-matched cohorts of statin initiators and non-initiators
using 1-year cohort accrual blocks. The variables used to create the propensity
score model included disease duration, body mass index, lifestyle factors,
comorbidities and medication use. RESULTS: Using unmatched AS cohorts, statin
initiators (n=1430) showed a 43% higher risk of mortality than non-initiators
(n=1430) (HR=1.43; 95% CI 1.12 to 1.84). After propensity score matching,
patients with AS who initiated statins (n=1108) had 96 deaths, and matched non
initiators (n=1108) had 134 deaths over a mean follow-up of 5.3 and 5.1 years,
respectively. This corresponded to mortality rates of 16.5 and 23.8 per 1000
person-years (PY), respectively, resulting in an HR of 0.63 (95% CI 0.46 to 0.85)
and an absolute mortality rate difference of 7.3 deaths per 1000 PY (95% CI 2.1
to 12.5). CONCLUSION: This general population-based cohort study suggests that
statin initiation is associated with a substantially lower risk of mortality
among patients with AS. The magnitude of the inverse association appears to be
larger than that observed in randomised trials of the general population and in
population-based cohort studies of patients with rheumatoid arthritis.
PMID- 28698232
TI - Genome-Wide Sequence and Expression Analysis of the NAC Transcription Factor
Family in Polyploid Wheat.
AB - Many important genes in agriculture correspond to transcription factors (TFs)
that regulate a wide range of pathways from flowering to responses to disease and
abiotic stresses. In this study, we identified 5776 TFs in hexaploid wheat
(Triticum aestivum) and classified them into gene families. We further
investigated the NAC family exploring the phylogeny, C-terminal domain (CTD)
conservation, and expression profiles across 308 RNA-seq samples. Phylogenetic
trees of NAC domains indicated that wheat NACs divided into eight groups similar
to rice (Oryza sativa) and barley (Hordeum vulgare). CTD motifs were frequently
conserved between wheat, rice, and barley within phylogenetic groups; however,
this conservation was not maintained across phylogenetic groups. Three
homeologous copies were present for 58% of NACs, whereas evidence of single
homeolog gene loss was found for 33% of NACs. We explored gene expression
patterns across a wide range of developmental stages, tissues, and abiotic
stresses. We found that more phylogenetically related NACs shared more similar
expression patterns compared to more distant NACs. However, within each
phylogenetic group there were clades with diverse expression profiles. We carried
out a coexpression analysis on all wheat genes and identified 37 modules of
coexpressed genes of which 23 contained NACs. Using gene ontology (GO) term
enrichment, we obtained putative functions for NACs within coexpressed modules
including responses to heat and abiotic stress and responses to water: these NACs
may represent targets for breeding or biotechnological applications. This study
provides a framework and data for hypothesis generation for future studies on NAC
TFs in wheat.
PMID- 28698234
TI - Sixty seconds on . . . sex with robots.
PMID- 28698233
TI - Reduced Protein Expression in a Virus Attenuated by Codon Deoptimization.
AB - A general means of viral attenuation involves the extensive recoding of
synonymous codons in the viral genome. The mechanistic underpinnings of this
approach remain unclear, however. Using quantitative proteomics and RNA
sequencing, we explore the molecular basis of attenuation in a strain of
bacteriophage T7 whose major capsid gene was engineered to carry 182 suboptimal
codons. We do not detect transcriptional effects from recoding. Proteomic
observations reveal that translation is halved for the recoded major capsid gene,
and a more modest reduction applies to several coexpressed downstream genes. We
observe no changes in protein abundances of other coexpressed genes that are
encoded upstream. Viral burst size, like capsid protein abundance, is also
decreased by half. Together, these observations suggest that, in this virus,
reduced translation of an essential polycistronic transcript and diminished
virion assembly form the molecular basis of attenuation.
PMID- 28698236
TI - Exploring Maize Leaf Architecture from Different Angles.
PMID- 28698238
TI - Protective factors for social-emotional well-being of refugee children in the
first three years of settlement in Australia.
AB - AIM: This longitudinal study investigated protective factors for social-emotional
well-being in refugee children in Australia. METHODS: Newly arrived refugee
children aged 4-15 years were recruited between 2009 and 2013 and assessments
were conducted at two points, at years 2 and 3 postarrival. Social-emotional well
being was assessed using the Strengths and Difficulties Questionnaire (SDQ).
Protective factors were assessed by structured interview and the Social
Readjustment Rating Scale (SRRS); scores <150 reflect fewer stressful life events
in the previous year. RESULTS: Forty-three eligible refugee children were
recruited. The SDQ was completed by parents in 90% and protective factor data in
80% at years 2 and 3 of follow-up. Protective factors for normal SDQ scores were:
originating from Africa (p=0.01), father present on arrival (p=0.019) and family
SRRS scores <150 at year 2 (p=0.045). The median number of protective factors was
4 (range 1-8). Better SDQ scores were associated with >=4 protective factors
(p<0.006). Furthermore, more protective factors increased the child's likelihood
of a stable or improved SDQ score over time (p<0.04). Modifiable protective
factors likely to promote social-emotional well-being include stability in the
child's school and residence, parental employment, financial and marital
stability, proximity to one's own ethnic community and external community
support. CONCLUSIONS: Cumulative protective factors, some of which are
potentially modifiable, can predict social-emotional well-being in newly arrived
refugee children. Children with four or more protective factors are at low risk
of poor social-emotional well-being.
PMID- 28698237
TI - Maize YABBY Genes drooping leaf1 and drooping leaf2 Regulate Plant Architecture.
AB - Leaf architecture directly influences canopy structure, consequentially affecting
yield. We discovered a maize (Zea mays) mutant with aberrant leaf architecture,
which we named drooping leaf1 (drl1). Pleiotropic mutations in drl1 affect leaf
length and width, leaf angle, and internode length and diameter. These phenotypes
are enhanced by natural variation at the drl2 enhancer locus, including reduced
expression of the drl2-Mo17 allele in the Mo17 inbred. A second drl2 allele,
produced by transposon mutagenesis, interacted synergistically with drl1 mutants
and reduced drl2 transcript levels. The drl genes are required for proper leaf
patterning, development and cell proliferation of leaf support tissues, and for
restricting auricle expansion at the midrib. The paralogous loci encode maize
CRABS CLAW co-orthologs in the YABBY family of transcriptional regulators. The
drl genes are coexpressed in incipient and emergent leaf primordia at the shoot
apex, but not in the vegetative meristem or stem. Genome-wide association studies
using maize NAM-RIL (nested association mapping-recombinant inbred line)
populations indicated that the drl loci reside within quantitative trait locus
regions for leaf angle, leaf width, and internode length and identified rare
single nucleotide polymorphisms with large phenotypic effects for the latter two
traits. This study demonstrates that drl genes control the development of key
agronomic traits in maize.
PMID- 28698239
TI - Enzymatic production of single-molecule FISH and RNA capture probes.
AB - Arrays of singly labeled short oligonucleotides that hybridize to a specific
target revolutionized RNA biology, enabling quantitative, single-molecule
microscopy analysis and high-efficiency RNA/RNP capture. Here, we describe a
simple and efficient method that allows flexible functionalization of inexpensive
DNA oligonucleotides by different fluorescent dyes or biotin using terminal
deoxynucleotidyl transferase and custom-made functional group conjugated dideoxy
UTP. We show that (i) all steps of the oligonucleotide labeling-including
conjugation, enzymatic synthesis, and product purification-can be performed in a
standard biology laboratory, (ii) the process yields >90%, often >95% labeled
product with minimal carryover of impurities, and (iii) the oligonucleotides can
be labeled with different dyes or biotin, allowing single-molecule FISH, RNA
affinity purification, and Northern blot analysis to be performed.
PMID- 28698240
TI - Beyond hormone replacement: quality of life in women with congenital
hypogonadotropic hypogonadism.
AB - OBJECTIVE: Little is known about how women with isolated GnRH deficiency cope
with their condition. This study aimed to examine the health and informational
needs of women with congenital hypogonadotropic hypogonadism (CHH) and evaluate
if their experiences differ from women with more common forms of infertility.
DESIGN: Cross-sectional, multiple methods study using web-based data collection
to reach dispersed rare disease patients. METHODS: A community-based
participatory research framework was employed to develop an online survey and
collect quantitative and qualitative data. Adult women diagnosed with CHH who had
received at least one year of hormonal treatment completed the Morisky Medication
Adherence Scale, Revised Illness Perception Questionnaire and Zung Self-Rating
Depression Scale. Information on health care experiences, treatment outcomes and
patient-reported challenges were also collected. RESULTS: Women (n = 55) were
often diagnosed late (20.7 +/- 7.4, range: 10-48 years) and 16/20 patients
receiving fertility treatment conceived. Poor adherence was frequently observed
(34/55) while more than half (27/49) reported a gap in treatment exceeding a
year. Low adherence correlated with depressive symptoms (r = 0.3, P > 0.05).
Negative illness perceptions were pervasive and 30/55 exhibited some depressive
symptoms - significantly greater than women with common female factor infertility
(P < 0.01). Symptoms were underappreciated by providers as only 15 of 55 patients
had discussions about psychological services. Women identified isolation, need
for information and finding expert care as challenges to living with CHH.
CONCLUSIONS: Despite being a treatable form of female infertility, the presumable
availability of treatment does not necessarily ensure adequate quality of life
for women with isolated GnRH deficiency.
PMID- 28698241
TI - Longitudinal characterisation of function and structure of Bietti crystalline
dystrophy: report on a novel homozygous mutation in CYP4V2.
AB - BACKGROUND: Bietti crystalline dystrophy (BCD) is a rare inherited disorder
characterised by fine crystalline deposits in the corneal limbus and retinal
posterior pole. In 2004, mutations in the CYP4V2 gene were identified as the
cause of BCD. Here, we describe the report of a homozygous point mutation in a
patient with BCD and provide detailed characterisation of functional and
structural changes over 20 years. METHODS: At regular intervals, the patient
underwent repeat ophthalmic evaluations. DNA was extracted from buccal swabs,
amplified by standard PCR and analysed for homology to the CYP4V2 sequence.
Homology modelling was conducted using Iterative Threading ASSEmbly Refinement
and molecular dynamics simulations using GROningen MAchine for Chemical
Simulations. RESULTS: The proband, a 47-year-old woman of German ancestry was
diagnosed with crystalline retinopathy at age 25. Over the next 20 years, visual
acuity and function gradually declined with progression of retinal pigment
epithelium and choroidal atrophy. When first tested at 39 years of age, the
multifocal electroretinogram (ERG) was markedly abnormal, more so for the right
eye, whereas the full-field ERG was more symmetrical and lagged other measures of
visual function. Gene sequencing showed a single C>T point mutation in exon 9
encoding a R400C amino acid change. Computational modelling suggests the mutation
impairs function due to loss of a hydrogen bonding interaction with the
propionate side chains of the haeme prosthetic group. CONCLUSION: This is the
first report of a homozygous R400C mutation in CYP4V2 with protein modelling
showing high likelihood of enzyme dysfunction. The comprehensive long-term
clinical follow-up provides insight into disease progression and highlights
possible anti-inflammatory modulation of disease severity.
PMID- 28698242
TI - Abnormal fixational eye movements in strabismus.
AB - INTRODUCTION: Fixational saccades are miniature eye movements that constantly
change the gaze during attempted visual fixation. Visually guided saccades and
fixational saccades represent an oculomotor continuum and are produced by common
neural machinery. Patients with strabismus have disconjugate binocular horizontal
saccades. We examined the stability and variability of eye position during
fixation in patients with strabismus and correlated the severity of fixational
instability with strabismus angle and binocular vision. METHODS: Eye movements
were measured in 13 patients with strabismus and 16 controls during fixation and
visually guided saccades under monocular viewing conditions. Fixational saccades
and intersaccadic drifts were analysed in the viewing and non-viewing eye of
patients with strabismus and controls. RESULTS: We found an increase in
fixational instability in patients with strabismus compared with controls. We
also found an increase in the disconjugacy of fixational saccades and
intrasaccadic ocular drift in patients with strabismus compared with controls.
The disconjugacy was worse in patients with large-angle strabismus and absent
stereopsis. There was an increase in eye position variance during drifts in
patients with strabismus. Our findings suggest that both fixational saccades and
intersaccadic drifts are abnormal and likely contribute to the fixational
instability in patients with strabismus. DISCUSSION: Fixational instability could
be a useful tool for mass screenings of children to diagnose strabismus in the
absence of amblyopia and latent nystagmus. The increased disconjugacy of
fixational eye movements and visually guided saccades in patients with strabismus
reflects the disruption of the fine-tuning of the motor and visual systems
responsible for achieving binocular fusion in these patients.
PMID- 28698243
TI - Influence of de qi on the immediate analgesic effect of SP6 acupuncture in
patients with primary dysmenorrhoea and cold and dampness stagnation: a
multicentre randomised controlled trial.
AB - OBJECTIVE: The aim of this multicentre randomised controlled trial was to
investigate the contribution of de qi to the immediate analgesic effect of
acupuncture in patients with primary dysmenorrhoea and the specific traditional
Chinese medicine diagnosis cold and dampness stagnation. METHOD: Eighty-eight
patients with primary dysmenorrhoea and cold and dampness stagnation were
randomly assigned to de qi (n=43) or no de qi (n=45) groups and underwent 30 min
of SP6 acupuncture. The de qi group received deep needling at SP6 with
manipulation using thick needles; the no de qi group received shallow needling
with no manipulation using thin needles. In both groups the pain scores and
actual de qi sensation were evaluated using a visual analogue scale for pain (VAS
P) and the acupuncture de qi clinical assessment scale (ADCAS), respectively.
RESULTS: Both groups showed reductions in VAS-P, with no signficant differences
between groups. ADCAS scores showed 43/43 and 25/45 patients in de qi and no de
qi groups, respectively, actually experienced de qi sensation. Independent of
original group allocation, VAS-P reductions associated with actual de qi (n=68)
were greater than those without (28.4+/-18.19 mm vs 14.6+/-12.28 mm, p=0.008).
CONCLUSIONS: This study showed no significant difference in VAS-P scores in
patients with primary dysmenorrhoea and cold and dampness stagnation immediately
after SP6 acupuncture designed to induce or avoid de qi sensation. Both
treatments significantly reduced VAS-P relative to baseline. Irrespective of
group allocation, patients experiencing actual de qi sensation demonstrated
larger reductions in pain score relative to those without, suggesting greater
analgesic effects. TRIAL REGISTRATION NUMBER: Chinese Clinical Trial Registry
(ChiCTR-TRC-13003086); Results.
PMID- 28698244
TI - Abortion terminology: views of women seeking abortion in Britain.
AB - BACKGROUND: Controversy exists as to whether 'abortion or 'termination of
pregnancy' should be used by health professionals during interactions with women
and in published works. METHODS: Self-administered anonymous questionnaires were
distributed to women attending 54 abortion clinics in Scotland, England and Wales
during a 4-month period in 2015. Responses were coded and analysed using SPSS.
Descriptive statistics were generated and responses compared by demographic
characteristics. The main outcome measures were the proportion of respondents
reporting that they found the terms 'abortion' and 'termination of pregnancy' to
be distressing, and women's preferred terminology for referring to induced
abortion. RESULTS: Surveys were completed by 2259 women. The mean age of the
respondents was 27(range 13-51) years; 82% identified as white, 51% had children
and 36% had previously undergone abortion. Thirty-five percent indicated that
they found the word 'abortion' distressing compared with 18% who reported that
'termination of pregnancy' was distressing (p< 0.001). Forty-five percent of
respondents expressed a preference for 'termination of pregnancy' and 12% for
'abortion'. Sixteen percent would choose either term. This pattern of results did
not vary statistically by age, reproductive history, country of residence,
ethnicity or level of deprivation. CONCLUSIONS: Most women seeking abortion did
not find the terms 'abortion' or termination of pregnancy' distressing. When
given a choice of terms, more women who expressed a preference chose 'termination
of pregnancy'. Healthcare professionals should be sensitive to preferences for
terminology when communicating with women seeking abortion.
PMID- 28698245
TI - Diet and Exercise and Serum Markers of Oxidative Stress-Letter.
PMID- 28698246
TI - Diet and Exercise and Serum Markers of Oxidative Stress-Response.
PMID- 28698247
TI - Carbohydrate-binding architecture of the multi-modular alpha-1,6
glucosyltransferase from Paenibacillus sp. 598K, which produces alpha-1,6
glucosyl-alpha-glucosaccharides from starch.
AB - Paenibacillus sp. 598K alpha-1,6-glucosyltransferase (Ps6TG31A), a member of
glycoside hydrolase family 31, catalyzes exo-alpha-glucohydrolysis and
transglucosylation and produces alpha-1,6-glucosyl-alpha-glucosaccharides from
alpha-glucan via its disproportionation activity. The crystal structure of
Ps6TG31A was determined by an anomalous dispersion method using a terbium
derivative. The monomeric Ps6TG31A consisted of one catalytic (beta/alpha)8
barrel domain and six small domains, one on the N-terminal and five on the C
terminal side. The structures of the enzyme complexed with maltohexaose,
isomaltohexaose, and acarbose demonstrated that the ligands were observed in the
catalytic cleft and the sugar-binding sites of four beta-domains. The catalytic
site was structured by a glucose-binding pocket and an aglycon-binding cleft
built by two sidewalls. The bound acarbose was located with its non-reducing end
pseudosugar docked in the pocket, and the other moieties along one sidewall
serving three subsites for the alpha-1,4-glucan. The bound
isomaltooligosaccharide was found on the opposite sidewall, which provided the
space for the acceptor molecule to be positioned for attack of the catalytic
intermediate covalent complex during transglucosylation. The N-terminal domain
recognized the alpha-1,4-glucan in a surface-binding mode. Two of the five C
terminal domains belong to the carbohydrate-binding modules family 35 and one to
family 61. The sugar complex structures indicated that the first family 35 module
preferred alpha-1,6-glucan, whereas the second family 35 module and family 61
module preferred alpha-1,4-glucan. Ps6TG31A appears to have enhanced
transglucosylation activity facilitated by its carbohydrate-binding modules and
substrate-binding cleft that positions the substrate and acceptor sugar for the
transglucosylation.
PMID- 28698248
TI - Ganglioside glycosyltransferases are S-acylated at conserved cysteine residues
involved in homodimerisation.
AB - Ganglioside glycosyltransferases (GGTs) are type II membrane proteins bearing a
short N-terminal cytoplasmic tail, a transmembrane domain (TMD), and a lumenal
catalytic domain. The expression and activity of these enzymes largely determine
the quality of the glycolipids that decorate mammalian cell membranes. Many
glycosyltransferases (GTs) are themselves glycosylated, and this is important for
their proper localisation, but few if any other post-translational modifications
of these proteins have been reported. Here, we show that the GGTs, ST3Gal-V,
ST8Sia-I, and beta4GalNAcT-I are S-acylated at conserved cysteine residues
located close to the cytoplasmic border of their TMDs. ST3Gal-II, a GT that
sialylates glycolipids and glycoproteins, is also S-acylated at a conserved
cysteine located in the N-terminal cytoplasmic tail. Many other GTs also possess
cysteine residues in their cytoplasmic regions, suggesting that this modification
occurs also on these GTs. S-acylation, commonly known as palmitoylation, is
catalysed by a family of palmitoyltransferases (PATs) that are mostly localised
at the Golgi complex but also at the endoplasmic reticulum (ER) and the plasma
membrane. Using GT ER retention mutants, we found that S-acylation of
beta4GalNAcT-I and ST3Gal-II takes place at different compartments, suggesting
that these enzymes are not substrates of the same PAT. Finally, we found that
cysteines that are the target of S-acylation on beta4GalNAcT-I and ST3Gal-II are
involved in the formation of homodimers through disulphide bonds. We observed an
increase in ST3Gal-II dimers in the presence of the PAT inhibitor 2
bromopalmitate, suggesting that GT homodimerisation may be regulating S
acylation.
PMID- 28698249
TI - PD vs HD in Post-Economic Crisis Greece-Differences in Patient Characteristics
and Estimation of Therapy Cost.
AB - OBJECTIVE: The aim of this study was to investigate patient characteristics and
make an estimation of the cost of peritoneal dialysis (PD) and hemodialysis (HD)
to Greek society during the economic crisis. METHODS: We recorded the
characteristics and the total cost of dialysis treatment in 100 patients on PD
and 100 on HD. Total costs included dialysis procedure, consumables, drugs,
laboratory tests, food, and transportation fees (only HD), covered by patients'
insurance. Also included were medical and administrative salaries, purchase and
maintenance of equipment and sanitary material, all covered by the state
hospital. RESULTS: The mean patient age was 64.5 +/- 16.8 years (PD) and 62.8 +/-
15.1 (HD) (p < 0,001). The most common cause of end-stage renal disease (ESRD)
was diabetes (32% for PD and 24% for HD patients). A total of 35% of the PD
patients were employed vs 4% of the HD patients (p < 0,001). The mean distance
from home for PD patients was 41.6 +/- 17.3 km, while for HD patients, it was 9.4
+/- 1.5 km (p < 0,001). Mean monthly cost for PD and HD treatment per patient was
?4,019.20 +/- 1,126.30 and ?3,254.30 +/- 37.50, respectively, both fully covered
by patients' insurance. Mean monthly cost for PD or HD dialysis unit maintenance
was ?11,660.80 and ?56,270.50, respectively, also fully covered by the state.
CONCLUSION: There is likely to be a considerable difference in terms of total
cost of PD vs HD therapy, owing to the fact that the operational cost of a PD
unit appears to be significantly lower than that of a HD unit.
PMID- 28698250
TI - Clinical Relevance of Intraperitoneal Pressure in Peritoneal Dialysis Patients.
AB - INTRODUCTION: Intraperitoneal pressure (IPP) in peritoneal dialysis (PD)
increases in sitting and upright positions and is related to some individual
characteristics. Adverse effects can appear with IPP > 20 cm H2O. Few studies
about peritoneal transport or abdominal wall problems have directly measured IPP.
We measured IPP in our prevalent PD patients to identify the clinical factors
related to its variability and its possible association with peritoneal transport
and abdominal wall complications. METHODS: We performed a retrospective,
observational study of our stable PD patients. Intraperitoneal pressure was
measured using the Durand's method in supine, sitting, and upright position.
RESULTS: Forty-nine patients were included, 70% males, mean age 61.1 +/- 15
years, body mass index (BMI) 27.9 +/- 5.2 kg/m2. The mean of supine IPP was 18.0
+/- 4.4 cm H2O. Intraperitoneal pressure in sitting and upright positions were
similar and higher than in supine. Supine IPP showed a positive correlation with
BMI (p < 0.0005) and comorbidity (p < 0.05). A multivariate linear regression
analysis showed that BMI and comorbidity (p < 0.005) had a positive correlation
with IPP; time on PD and daily total ultrafiltration (UF) (p < 0.005) showed a
negative correlation. Patients with an IPP >= 20 cm H2O had more hernias (35% vs
17%) and leakages (21% vs 8%) without statistical significance. CONCLUSION: Our
supine IPPs were higher than others published in adults. Intraperitoneal pressure
has an individual value associated with body size. Greater IPP was correlated
with lower daily total UF and more hernias and leakages. The measurement of IPP
is a simple technique and can help with PD prescription, especially in obese
patients.
PMID- 28698251
TI - TRPA1 Mechanoreceptors Mediate the IL-6 Response to a Single PD Dwell in the Rat.
AB - BACKGROUND: The development of modern, biocompatible peritoneal dialysis (PD)
fluids has not entirely eliminated the local pro-inflammatory effects of PD fluid
administration. The present study was performed in order to establish the
importance of known signaling pathways connected to mechano-, osmo- and chemo
sensors of the transient receptor potential (TRP) family for the acute
inflammatory response to PD. METHODS: Rats were exposed to a single 4-hour dwell
of lactate-buffered, 2.5% glucose, filter-sterilized PD fluid through an
implanted PD catheter. In some groups, the PD dwell was preceded by intravenous
administration of blockers of TRPV1 (BCTC), TRPA1 (HC030031), or neurokinin 1
(NK1) (Spantide II) receptors. Cytokine messenger ribonucleic acid (mRNA)
expressions were quantified in tissue biopsies (real-time polymerase chain
reaction [qPCR]), and cytokine concentrations were quantified in dialysate
samples by enzyme-linked immunosorbent assay (ELISA). Tissue expressions of
TRPV1, TRPA1, and NK1 were evaluated immuno-histochemically. RESULTS: The PD
dwell induced peritoneal synthesis of Il1b, Tnf, and Il6 and a secretion of
interleukin-6 (IL-6) into the dialysate. The catheter implantation already
induced the transcription of Il1b and Tnf but did not significantly affect Il6
transcription. The Il6 response to the PD dwell could be virtually eliminated by
blocking TRPA1 but was not affected by TRPV1 blockade. Blocking the substance P
receptor, NK1, produced an insignificant trend towards Il6 inhibition. TRPA1 and
NK1 showed a stronger immuno-reactivity than TRPV1 on cells of the peritoneal
tissue. CONCLUSION: The results show that IL-6 synthesis and secretion were
connected to acute PD fluid exposure, and this response was triggered by TRPA1
receptors, possibly located to non-neuronal cells.
PMID- 28698252
TI - Peritoneal Equilibration Test Reference Values Using a 3.86% Glucose Solution
During the First Year of Peritoneal Dialysis: Results of a Multicenter Study of a
Large Patient Population.
AB - BACKGROUND: The original peritoneal equilibration test (PET) was used to classify
peritoneal dialysis (PD) patients using a 2.27% glucose solution. It has since
been suggested that a 3.86% glucose solution be used because this provides better
information about ultrafiltration (UF) capacity and the sodium (Na) sieving of
the peritoneal membrane. OBJECTIVE: The aim of this study was to determine
reference values for a PET using a 3.86% glucose solution (PET-3.86%). METHODS:
We evaluated the PET-3.86% in a large population of incident PD patients
attending 27 Italian dialysis centers. RESULTS: We evaluated the results of 758
PET-3.86% in 758 incident PD patients (1 test per patient). The mean duration of
PD was 5 +/- 3 months. The ratio of the concentrations of creatinine in
dialysate/plasma (D/PCreat) was 0.73 +/- 0.1 (median 0.74). The ratio between the
concentrations of glucose at the end/beginning of the test (D/D0) was 0.25 +/-
0.08 (median 0.24). Ultrafiltration uncorrected and corrected for bag overfill
was respectively 776 +/- 295 mL (median 781 mL) and 675 +/- 308 mL (median 689
mL). Sodium sieving was 8.4 +/- 3.8 mmol/L (median 8.0 mmol/L). CONCLUSION: The
results of the study provide PET-3.86% reference values for the beginning of PD
that can be used to classify PD patients into transport classes and monitor them
over time.
PMID- 28698253
TI - Outcomes of Corynebacterium Peritonitis: A Multicenter Registry Analysis.
AB - BACKGROUND: Corynebacterium is a rare cause of peritonitis that is increasingly
being recognized in peritoneal dialysis (PD) patients. The aims of this study
were to compare Corynebacterium peritonitis outcomes with those of peritonitis
caused by other organisms and to examine the effects of type and duration of
antibiotic therapy on outcomes of Corynebacterium peritonitis. METHODS: Using
Australia and New Zealand Dialysis and Transplant Registry (ANZDATA) data, we
included all PD patients who developed peritonitis in Australia between 2004 and
2014. The primary outcome was peritonitis cure by antibiotic therapy, defined as
resolution of a peritonitis episode with antibiotics alone and without being
complicated by recurrence, relapse, catheter removal, hemodialysis transfer, or
death. Peritonitis outcomes were analyzed using multivariable logistic
regression. RESULTS: A total of 11,122 episodes of peritonitis in 5,367 patients
were included. Of these, 162 episodes (1.5%) were due to Corynebacterium.
Compared with Corynebacterium peritonitis, the odds of cure were lower in
peritonitis due to Staphylococcus aureus (odds ratio [OR] 0.66, 95% confidence
interval [CI] 0.45 - 0.97), Pseudomonas (OR 0.22, 95% CI 0.14 - 0.33), other gram
negative organisms (OR 0.52, 95% CI 0.35 - 0.75), fungi (OR 0.02, 95% CI 0.01 -
0.03), polymicrobial organisms (OR 0.32, 95% CI 0.22 - 0.47), and other organisms
(OR 0.66, 95% CI 0.44 - 0.99) but similar for culture-negative and other gram
positive peritonitis. Similar results were observed for hemodialysis transfer and
death. The outcomes of Corynebacterium peritonitis were not associated with the
type of initial antibiotic selected (vancomycin vs cefazolin) or the duration of
antibiotic therapy (<= 14 days vs > 14 days). CONCLUSIONS: Outcomes for
Corynebacterium peritonitis are generally favorable compared with other forms of
peritonitis. Cure rates did not appear to differ if peritonitis was treated
initially with vancomycin or cefazolin or if treatment duration was prolonged
beyond 14 days.
PMID- 28698254
TI - Mechanism-Based Pharmacokinetic/Pharmacodynamic Modeling of the Glucagon-Like
Peptide-1 Receptor Agonist Exenatide to Characterize Its Antiobesity Effects in
Diet-Induced Obese Mice.
AB - In addition to their potent antidiabetic effects, glucagon-like peptide-1 (GLP-1)
analogs lower body weight in humans. Hence, agonistic targeting of the GLP-1
receptor could be a valid approach to target obesity. However, quantitative
analyses of the pharmacokinetic/pharmacodynamic (PK/PD) relationship between GLP
1 analogs and their antiobesity effect have not been reported in either animals
or humans. Therefore, the present study was performed to establish a mechanism
based PK/PD model of GLP-1 receptor agonists using the GLP-1 analog exenatide for
the development of promising new antiobesity drugs. Exenatide was administered to
high-fat diet-induced obese C57BL/6J mice via subcutaneous bolus and continuous
infusion. Food intake and body-weight reductions were observed and depended on
the plasma concentrations of exenatide. The homeostatic feedback model, in which
food intake is assumed to be regulated by appetite control signals, described the
relationship among the plasma concentration-time profile of exenatide, food
intake, and body weight. The estimated IC50 of exenatide against food intake was
2.05 pM, which is similar to the reported KD value of exenatide in rat brain and
the estimated EC50 value for augmentation of insulin secretion in humans. The
PK/PD model simulation indicated that subcutaneous infusion would show a stronger
effect on body-weight reduction than bolus dosing would. This novel, quantitative
PK/PD model could be used for antiobesity research and development of GLP-1
analogs, GLP-1 secretagogues, GLP-1 degradation inhibitors, and combinations
thereof by allowing the estimation of appropriate pharmacokinetic profiles and
dosing regimens.
PMID- 28698255
TI - William M. Feinberg Award for Excellence in Clinical Stroke: Big Pictures and
Small Vessels.
PMID- 28698256
TI - Neutrophil-Lymphocyte Ratio and Perihematomal Edema Growth in Intracerebral
Hemorrhage.
AB - BACKGROUND AND PURPOSE: Although preclinical studies have shown inflammation to
mediate perihematomal edema (PHE) after intracerebral hemorrhage, clinical data
are lacking. Leukocyte count, often used to gauge serum inflammation, has been
correlated with poor outcome but its relationship with PHE remains unknown. Our
aim was to test the hypothesis that leukocyte count is associated with PHE
growth. METHODS: We included patients with intracerebral hemorrhage admitted to a
tertiary-care stroke center between 2011 and 2015. The primary outcome was
absolute PHE growth during 24 hours, calculated using semiautomated planimetry.
Linear regression models were constructed to study the relationship between
absolute and differential leukocyte counts (monocyte count and neutrophil
lymphocyte ratio) and 24-hour PHE growth. RESULTS: A total of 153 patients were
included. Median hematoma and PHE volumes at baseline were 14.4 (interquartile
range, 6.3-36.3) and 14.0 (interquartile range, 5.9-27.8), respectively. In
linear regression analysis adjusted for demographics and intracerebral hemorrhage
characteristics, absolute leukocyte count was not associated with PHE growth
(beta, 0.07; standard error, 0.15; P=0.09). In secondary analyses, neutrophil
lymphocyte ratio was correlated with PHE growth (beta, 0.22; standard error,
0.08; P=0.005). CONCLUSIONS: Higher neutrophil-lymphocyte ratio is independently
associated with PHE growth. This suggests that PHE growth can be predicted using
differential leukocyte counts on admission.
PMID- 28698257
TI - Brain Transforming Growth Factor-beta Resists Hypertension Via Regulating
Microglial Activation.
AB - BACKGROUND AND PURPOSE: Hypertension is the major risk factor for stroke. Recent
work unveiled that hypertension is associated with chronic neuroinflammation;
microglia are the major players in neuroinflammation, and the activated microglia
elevate sympathetic nerve activity and blood pressure. This study is to
understand how brain homeostasis is kept from hypertensive disturbance and
microglial activation at the onset of hypertension. METHODS: Hypertension was
induced by subcutaneous delivery of angiotensin II, and blood pressure was
monitored in conscious animals. Microglial activity was analyzed by flow
cytometry and immunohistochemistry. Antibody, pharmacological chemical, and
recombinant cytokine were administered to the brain through
intracerebroventricular infusion. Microglial depletion was performed by
intracerebroventricular delivering diphtheria toxin to CD11b-diphtheria toxin
receptor mice. Gene expression profile in sympathetic controlling nucleus was
analyzed by customized qRT-PCR array. RESULTS: Transforming growth factor-beta
(TGF-beta) is constitutively expressed in the brains of normotensive mice.
Removal of TGF-beta or blocking its signaling before hypertension induction
accelerated hypertension progression, whereas supplementation of TGF-beta1
substantially suppressed neuroinflammation, kidney norepinephrine level, and
blood pressure. By means of microglial depletion and adoptive transfer, we showed
that the effects of TGF-beta on hypertension are mediated through microglia. In
contrast to the activated microglia in established hypertension, the resting
microglia are immunosuppressive and important in maintaining neural homeostasis
at the onset of hypertension. Further, we profiled the signature molecules of
neuroinflammation and neuroplasticity associated with hypertension and TGF-beta
by qRT-PCR array. CONCLUSIONS: Our results identify that TGF-beta-modulated
microglia are critical to keeping brain homeostasis responding to hypertensive
disturbance.
PMID- 28698258
TI - Comparison of Fatal or Irreversible Events With Extended-Duration Betrixaban
Versus Standard Dose Enoxaparin in Acutely Ill Medical Patients: An APEX Trial
Substudy.
AB - BACKGROUND: Extended-duration betrixaban showed a significant reduction in venous
thromboembolism in the APEX trial (Acute Medically Ill VTE Prevention With
Extended Duration Betrixaban Study). Given the variable clinical impact of
different efficacy and safety events, one approach to assess net clinical
outcomes is to include only those events that are either fatal or cause
irreversible harm. METHODS AND RESULTS: This was a post hoc analysis of the APEX
trial-a multicenter, double-blind, randomized controlled trial comparing extended
duration betrixaban versus standard-of-care enoxaparin. A composite of all fatal
or irreversible safety (fatal bleeding or intracranial hemorrhage) and efficacy
events (cardiopulmonary death, myocardial infarction, pulmonary embolism, and
ischemic stroke) was evaluated in a time-to-first event analysis. In patients
with positive D-dimer results, betrixaban reduced fatal or irreversible events at
35 to 42 days (4.80% versus 3.54%; hazard ratio, 0.73; absolute risk reduction,
1.26%; number needed to treat, 79 [P=0.033]) and at study end at 77 days (6.27%
versus 4.36%; hazard ratio, 0.70; absolute risk reduction, 1.91%; number needed
to treat, 52 [P=0.005]) versus enoxaparin. In all patients, betrixaban reduced
fatal or irreversible events at 35 to 42 days (4.08% versus 2.90%; hazard ratio,
0.71; absolute risk reduction, 1.18%; number needed to treat, 86 [P=0.006]) and
77 days (5.17% versus 3.64%; hazard ratio, 0.70; absolute risk reduction, 1.53%;
number needed to treat, 65 [P=0.002]). CONCLUSIONS: Among hospitalized medically
ill patients, extended-duration betrixaban demonstrated an ~30% reduction in
fatal or irreversible ischemic or bleeding events compared with standard-duration
enoxaparin. A total of 65 patients would require treatment with betrixaban to
prevent 1 fatal or irreversible event versus enoxaparin. CLINICAL TRIAL
REGISTRATION: URL: http://www.ClinicalTrials.gov. Unique identifier: NCT01583218.
PMID- 28698259
TI - Reversibility of Cardiac Function Predicts Outcome After Transcatheter Aortic
Valve Replacement in Patients With Severe Aortic Stenosis.
AB - BACKGROUND: Reversibility of left ventricular (LV) dysfunction in high-risk
aortic stenosis patient and its impact on survival after transcatheter aortic
valve replacement (TAVR) are unclear. We aimed to evaluate longitudinal changes
of LV structure and function after TAVR and their impact on survival. METHODS AND
RESULTS: We studied 209 patients with aortic stenosis who underwent TAVR from May
2006 to December 2012. Echocardiograms were used to calculate LV end-diastolic
volume index (LVEDVi), LV ejection fraction, LV mass index (LVMi), and global
longitudinal strain before, immediately (<10 days), late (1-3 months), and yearly
after TAVR. During a median follow-up of 1345 days, 118 patients died, with 26
dying within 1 year. Global longitudinal strain, LVEDVi, LV ejection fraction,
and LVMi improved during follow-up. In patients who died during the first year,
death was preceded by LVEDVi and LVMi increase. Multivariable longitudinal data
analysis showed that aortic regurgitation at baseline, aortic regurgitation at 30
days, and initial LVEDVi were independent predictors of subsequent LVEDVi. In a
joint analysis of longitudinal and survival data, baseline Society of Thoracic
Surgeons score was predictive of survival, with no additive effect of
longitudinal changes in LVEDVi, LVMi, global longitudinal strain, or LV ejection
fraction. Presence of aortic regurgitation at 1 month after TAVR was the only
predictor of 1-year survival. CONCLUSIONS: LV reverse remodeling was observed
after TAVR, whereas lack of LVEDVi and LVMi improvement was observed in patients
who died during the first year after TAVR. Post-TAVR, aortic regurgitation blocks
reverse remodeling and is associated with poor 1-year survival after TAVR.
PMID- 28698260
TI - Phospholipase Cgamma1 Mediates Intima Formation Through Akt-Notch1 Signaling
Independent of the Phospholipase Activity.
AB - BACKGROUND: Vascular smooth muscle cell proliferation, migration, and
dedifferentiation are critical for vascular diseases. Recently, it was
demonstrated that Notch receptors have opposing effects on intima formation after
vessel injury. Therefore, it is important to investigate the specific regulatory
pathways that activate the different Notch receptors. METHODS AND RESULTS: There
was a time- and dose-dependent activation of Notch1 by angiotensin II and
platelet-derived growth factor in vascular smooth muscle cells. When
phospholipase Cgamma1 (PLCgamma1) expression was reduced by small interfering
RNA, Notch1 activation and Hey2 expression (Notch target gene) induced by
angiotensin II or platelet-derived growth factor were remarkably inhibited, while
Notch2 degradation was not affected. Mechanistically, we observed an association
of PLCgamma1 and Akt, which increased after angiotensin II or platelet-derived
growth factor stimulation. PLCgamma1 knockdown significantly inhibited Akt
activation. Importantly, PLCgamma1 phospholipase site mutation (no phospholipase
activity) did not affect Akt activation. Furthermore, PLCgamma1 depletion
inhibited platelet-derived growth factor-induced vascular smooth muscle cell
proliferation, migration, and dedifferentiation, while it increased apoptosis. In
vivo, PLCgamma1 and control small interfering RNA were delivered
periadventitially in pluronic gel and complete carotid artery ligation was
performed. Morphometric analysis 21 days after ligation demonstrated that
PLCgamma1 small interfering RNA robustly attenuated intima area and intima/media
ratio compared with the control group. CONCLUSIONS: PLCgamma1-Akt-mediated Notch1
signaling is crucial for intima formation. This effect is attributable to
PLCgamma1-Akt interaction but not PLCgamma1 phospholipase activity. Specific
inhibition of the PLCgamma1 and Akt interaction will be a promising therapeutic
strategy for preventing vascular remodeling.
PMID- 28698261
TI - Adipocyte-Specific Deficiency of De Novo Sphingolipid Biosynthesis Leads to
Lipodystrophy and Insulin Resistance.
AB - Sphingolipids have been implicated in the etiology of chronic metabolic diseases.
Here, we investigated whether sphingolipid biosynthesis is associated with the
development of adipose tissues and metabolic diseases. SPTLC2, a subunit of
serine palmitoyltransferase, was transcriptionally upregulated in the adipose
tissues of obese mice and in differentiating adipocytes. Adipocyte-specific
SPTLC2-deficient (aSPTLC2 KO) mice had markedly reduced adipose tissue mass.
Fatty acids that were destined for the adipose tissue were instead shunted to
liver and caused hepatosteatosis. This impaired fat distribution caused systemic
insulin resistance and hyperglycemia, indicating severe lipodystrophy.
Mechanistically, sphingosine 1-phosphate (S1P) was reduced in the adipose tissues
of aSPTLC2 KO mice, and this inhibited adipocyte proliferation and
differentiation via the downregulation of S1P receptor 1 and decreased activity
of the peroxisome proliferator-activator receptor gamma. In addition,
downregulation of SREBP (sterol regulatory element-binding protein)-1c prevented
adipogenesis of aSPTLC2 KO adipocytes. Collectively, our observations suggest
that the tight regulation of de novo sphingolipid biosynthesis and S1P signaling
plays an important role in adipogenesis and hepatosteatosis.
PMID- 28698262
TI - Thyroid Hormone Coordinates Pancreatic Islet Maturation During the Zebrafish
Larval-to-Juvenile Transition to Maintain Glucose Homeostasis.
AB - Thyroid hormone (TH) signaling promotes tissue maturation and adult organ
formation. Developmental transitions alter an organism's metabolic requirements,
and it remains unclear how development and metabolic demands are coordinated. We
used the zebrafish as a model to test whether and how TH signaling affects
pancreatic islet maturation, and consequently glucose homeostasis, during the
larval to juvenile transition. We found that exogenous TH precociously activates
the beta-cell differentiation genes pax6b and mnx1 while downregulating arxa, a
master regulator of alpha-cell development and function. Together, these effects
induced hypoglycemia, at least in part by increasing insulin and decreasing
glucagon expression. We visualized TH target tissues using a novel TH-responsive
reporter line and found that both alpha- and beta-cells become targets of
endogenous TH signaling during the larval-to-juvenile transition. Importantly,
endogenous TH is required during this transition for the functional maturation of
alpha- and beta-cells in order to maintain glucose homeostasis. Thus, our study
sheds new light on the regulation of glucose metabolism during major
developmental transitions.
PMID- 28698263
TI - Ventilator-Induced Diaphragmatic Dysfunction: Diagnosis and Role of
Pharmacological Agents.
AB - The use of controlled mechanical ventilation results in a major reduction of
diaphragmatic contractile force together with atrophy of diaphragm muscle fibers,
which is a condition known as ventilator-induced diaphragmatic dysfunction.
Ventilator-induced diaphragmatic dysfunction is one of the major contributors to
weaning difficulties and even increased mortality. This review summarizes the
current data on the pathogenesis and diagnosis of ventilator-induced
diaphragmatic dysfunction, and it outlines the use of ultrasonography for
diaphragm evaluation. In addition, current pharmacologic agents used to mitigate
ventilator-induced diaphragmatic dysfunction are described, with a particular
emphasis on the therapeutic potential of theophylline in patients with ventilator
induced diaphragmatic dysfunction-associated weaning difficulties.
PMID- 28698264
TI - Modeling of Lung Function Recovery in Neuralgic Amyotrophy With Diaphragm
Impairment.
AB - BACKGROUND: Neuralgic amyotrophy is an inflammatory peripheral nerve disorder in
which phrenic nerve involvement can lead to diaphragm paralysis. The prevalence,
magnitude, and time course of diaphragm recovery are uncertain. METHODS: This
study modeled the course of recovery of lung function in 16 subjects with
diaphragm impairment from neuralgic amyotrophy. The first and last available
vital capacity, sitting-to-supine decline in vital capacity, and maximal
inspiratory pressures were compared. RESULTS: An asymptotic regression model
analysis in 11 subjects with at least partial recovery provided estimates of the
vital capacity at onset (47%, 95% CI 25-68%), the final vital capacity (81%, 95%
CI 62-101%), and the half-time to recovery (22 months, 95% CI 15-43 months). In
those subjects, there was a significant improvement between the first and last
measured FVC (median 44-66%, P = .004) and maximal inspiratory pressure (mean 34
51%, P = .004). Five subjects (31%) with complete recovery had a final sitting-to
supine drop of vital capacity of 16% and a maximal predicted inspiratory pressure
of 63%. CONCLUSIONS: Sixty-nine percent of subjects with diaphragm impairment
from neuralgic amyotrophy experience recovery of lung function and diaphragm
strength, but recovery is slow and may be incomplete.
PMID- 28698266
TI - Spirometry, Static Lung Volumes, and Diffusing Capacity.
AB - BACKGROUND: Spirometric Z-scores from the Global Lung Initiative (GLI) rigorously
account for age-related changes in lung function and are thus age-appropriate
when establishing spirometric impairments, including a restrictive pattern and
air-flow obstruction. However, GLI-defined spirometric impairments have not yet
been evaluated regarding associations with static lung volumes (total lung
capacity [TLC], functional residual capacity [FRC], and residual volume [RV]) and
gas exchange (diffusing capacity). METHODS: We performed a retrospective review
of pulmonary function tests in subjects >=40 y old (mean age 64.6 y), including
pre-bronchodilator measures for: spirometry (n = 2,586), static lung volumes by
helium dilution with inspiratory capacity maneuver (n = 2,586), and hemoglobin
adjusted single-breath diffusing capacity (n = 2,508). Using multivariable linear
regression, adjusted least-squares means (adjLSMeans) were calculated for TLC,
FRC, RV, and hemoglobin-adjusted single-breath diffusing capacity. The adjLSMeans
were expressed with and without height-cubed standardization and stratified by
GLI-defined spirometry, including normal (n = 1,251), restrictive pattern (n =
663), and air-flow obstruction (mild, [n = 128]; moderate, [n = 150]; and severe,
[n = 394]). RESULTS: Relative to normal spirometry, restrictive-pattern had lower
adjLSMeans for TLC, FRC, RV, and hemoglobin-adjusted single-breath diffusing
capacity (P <= .001). Conversely, relative to normal spirometry, mild, moderate,
and severe air-flow obstruction had higher adjLSMeans for FRC and RV (P < .001).
However, only mild and moderate air-flow obstruction had higher adjLSMeans for
TLC (P < .001), while only moderate and severe air-flow obstruction had higher
adjLSMeans for RV/TLC (P < .001) and lower adjLSMeans for hemoglobin-adjusted
single-breath diffusing capacity (P < .001). Notably, TLC (calculated as FRC +
inspiratory capacity) was not increased in severe air-flow obstruction (P >= .11)
because inspiratory capacity decreased with increasing air-flow obstruction (P <
.001), thus opposing the increased FRC (P < .001). Finally, P values were similar
whether adjLSMeans were height-cubed standardized. CONCLUSIONS: A GLI-defined
spirometric restrictive pattern is strongly associated with a restrictive
ventilatory defect (decreased TLC, FRC, and RV), while GLI-defined spirometric
air-flow obstruction is strongly associated with hyperinflation (increased FRC)
and air trapping (increased RV and RV/TLC). Both spirometric impairments were
strongly associated with impaired gas exchange (decreased hemoglobin-adjusted
single-breath diffusing capacity).
PMID- 28698267
TI - Clinical Criteria for Tracheostomy Decannulation in Subjects with Acquired Brain
Injury.
AB - BACKGROUND: Patients with acquired brain injury (ABI) often require long periods
of having a tracheostomy tube for airway protection and prolonged mechanical
ventilation. It has been recognized that fast and safe decannulation improves
outcomes and facilitates the recovery process. Nevertheless, few studies have
provided evidence for decannulation criteria, despite the high prevalence of ABI
subjects with tracheostomies. The aim of our study was to assess which clinical
parameters are the best predictors for decannulation in subjects with ABI.
METHODS: In this cross-sectional study, we recruited 74 consecutive ABI subjects
(mean age 51.52 +/- 16.76) with tracheostomy tubes. First, the subjects underwent
the original decannulation assessment for cannula removal. Second, they underwent
our experimental decannulation protocol. The experimental protocol included:
voluntary cough (cough peak flow >=160 L/min), reflex cough, tracheostomy tube
capping (>=72 h), swallowing instrumental assessment (penetration aspiration
scale <=5), blue dye test, number of trachea suctions, endoscopic assessment of
airway patency (lumen diameter >=50%), saturation (SpO2 >95%), and level of
consciousness evaluation (Glasgow coma scale >=8). The reference standard was
clinical removal of the tracheostomy tube within 48 h. RESULTS: Parameters
showing the highest values of sensitivity and specificity, respectively, were
tracheostomy tube capping (80%, 100%), endoscopy assessment of airway patency
(100%, 30%), swallowing instrumental assessment (85%, 96%), and the blue dye test
(65%, 85%). All these were combined in a clinical cluster parameter, which had
higher sensitivity (100%) and specificity (82%). CONCLUSION: These results
suggest that the best clinical prediction rule for decannulation in acquired
brain injury subjects is a combination of the following assessments: (1)
tracheostomy tube capping, (2) endoscopic assessment of patency of airways, (3)
swallowing instrumental assessment, and (4) blue dye test.
PMID- 28698268
TI - Effects of Volume Guaranteed Ventilation Combined with Two Different Modes in
Preterm Infants.
AB - BACKGROUND: Volume-controlled ventilation modes have been shown to reduce
duration of mechanical ventilation, incidence of chronic lung disease, failure of
primary mode of ventilation, hypocarbia, severe intraventricular hemorrhage,
pneumothorax, and periventricular leukomalacia in preterm infants when compared
with pressure limited ventilation modes. Volume-guarantee (VG) ventilation is the
most commonly used mode for volume-controlled ventilation. Assist control,
pressure-support ventilation (PSV), and synchronized intermittent mandatory
ventilation (SIMV) can be combined with VG; however, there is a lack of knowledge
on the superiority of each regarding clinical outcomes. Therefore, we
investigated the effects of SIMV+VG and PSV+VG on ventilatory parameters,
pulmonary inflammation, morbidity, and mortality in preterm infants. METHODS:
Preterm infants who were born in our hospital between 24-32 weeks gestation and
needed mechanical ventilation for respiratory distress syndrome were considered
eligible. Patients requiring high-frequency oscillatory ventilation for primary
treatment were excluded. Subjects were randomized to either SIMV+VG or PSV+VG.
Continuously recorded ventilatory parameters, clinical data, blood gas values,
and tracheal aspirate cytokine levels were analyzed. RESULTS: The study enrolled
42 subjects. Clinical data were similar between groups. PSV+VG delivered closer
tidal volumes to set tidal volumes (60% vs 49%, P = .02). Clinical data,
including days on ventilation, morbidity, and mortality, were similar between
groups. Chronic lung disease occurred less often and heart rate was lower in
subjects who were ventilated with PSV+VG. The incidence of hypocarbia and
hypercarbia were similar. Interleukin-1beta in the tracheal aspirates increased
during both modes. CONCLUSION: PSV+VG provided closer tidal volumes to the set
value in ventilated preterm infants with respiratory distress syndrome and was
not associated with overventilation or a difference in mortality or morbidity
when compared to SIMV+VG. Therefore, PSV+VG is a safe mode of mechanical
ventilation to be used for respiratory distress syndrome.
PMID- 28698269
TI - Urinary Matrix Metalloproteinase-7 Predicts Severe AKI and Poor Outcomes after
Cardiac Surgery.
AB - Urinary matrix metalloproteinase-7 (uMMP-7) levels consistently reflect the
activity of intrarenal Wnt/beta-catenin, which is activated in AKI models. To
test the hypothesis that uMMP-7 is a predictor for severe AKI in patients after
cardiac surgery, we performed a prospective, multicenter, two-stage cohort study
in 721 patients undergoing cardiac surgery. In stage 1, we enrolled 323 children
from three academic medical centers. In stage 2, we enrolled 398 adults at six
centers. We analyzed levels of uMMP-7 and other injury biomarkers during the
perioperative period. Severe AKI was defined as Kidney Disease Improving Global
Outcomes stage 2 or 3. uMMP-7 level peaked within 6 hours after surgery in
patients who subsequently developed severe AKI. After multivariate adjustment,
the highest quintile of postoperative uMMP-7 level, compared with the lowest
quintile, associated with 17-fold (in adults) and 36-fold (in children) higher
odds of severe AKI. Elevated uMMP-7 level associated with increased risk of
composite events (severe AKI, acute dialysis, and in-hospital death) and longer
stay in the intensive care unit and hospital. For predicting severe AKI, uMMP-7
had an area under the receiver operating characteristic curve of 0.81 (in
children) and 0.76 (in adults), outperforming urinary IL-18, angiotensinogen,
neutrophil gelatinase-associated lipocalin, albumin-to-creatinine ratio, and
tissue inhibitor of metalloproteinase-2.IGF-binding protein-7 and the clinical
model. uMMP-7 significantly improved risk reclassification over the clinical
model alone, as measured by net reclassification improvement and integrated
discrimination improvement. In conclusion, uMMP-7 is a promising predictor for
severe AKI and poor in-hospital outcomes in patients after cardiac surgery.
PMID- 28698265
TI - Risk Factors for Noninvasive Ventilation Failure in Critically Ill Subjects With
Confirmed Influenza Infection.
AB - BACKGROUND: Despite wide use of noninvasive ventilation (NIV) in several clinical
settings, the beneficial effects of NIV in patients with hypoxemic acute
respiratory failure (ARF) due to influenza infection remain controversial. The
aim of this study was to identify the profile of patients with risk factors for
NIV failure using chi-square automatic interaction detection (CHAID) analysis and
to determine whether NIV failure is associated with ICU mortality. METHODS: This
work was a secondary analysis from prospective and observational multi-center
analysis in critically ill subjects admitted to the ICU with ARF due to influenza
infection requiring mechanical ventilation. Three groups of subjects were
compared: (1) subjects who received NIV immediately after ICU admission for ARF
and then failed (NIV failure group); (2) subjects who received NIV immediately
after ICU admission for ARF and then succeeded (NIV success group); and (3)
subjects who received invasive mechanical ventilation immediately after ICU
admission for ARF (invasive mechanical ventilation group). Profiles of subjects
with risk factors for NIV failure were obtained using CHAID analysis. RESULTS: Of
1,898 subjects, 806 underwent NIV, and 56.8% of them failed. Acute Physiology and
Chronic Health Evaluation II (APACHE II) score, Sequential Organ Failure
Assessment (SOFA) score, infiltrates in chest radiograph, and ICU mortality
(38.4% vs 6.3%) were higher (P < .001) in the NIV failure than in the NIV success
group. SOFA score was the variable most associated with NIV failure, and 2
cutoffs were determined. Subjects with SOFA >= 5 had a higher risk of NIV failure
(odds ratio = 3.3, 95% CI 2.4-4.5). ICU mortality was higher in subjects with NIV
failure (38.4%) compared with invasive mechanical ventilation subjects (31.3%, P
= .018), and NIV failure was associated with increased ICU mortality (odds ratio
= 11.4, 95% CI 6.5-20.1). CONCLUSIONS: An automatic and non-subjective algorithm
based on CHAID decision-tree analysis can help to define the profile of patients
with different risks of NIV failure, which might be a promising tool to assist in
clinical decision making to avoid the possible complications associated with NIV
failure.
PMID- 28698270
TI - Association between Endothelin-1 Levels and Kidney Disease among Blacks.
AB - Endothelin-1, a marker of endothelial dysfunction, is a potent vasoconstrictor
released by endothelial cells and an important regulator of renal physiology. It
is not known whether elevated serum levels of endothelin-1 indicate future risk
of kidney disease in the general population. In participants in the Jackson Heart
Study, a community-based observational study of cardiovascular risk in black
adults, we measured serum endothelin-1 level at baseline (2000-2004; n=3538). We
defined incident CKD as eGFR<60 ml/min per 1.73 m2 and >=30% eGFR decline at the
third visit (2009-2013) relative to baseline among those participants with
baseline eGFR >=60 ml/min per 1.73 m2 At baseline, mean age was 55 years old, 37%
of participants were men, and mean eGFR was 94 ml/min per 1.73 m2 Over a median
follow-up of 8 years, 228 (6.4%) cases of incident CKD occurred in participants.
Participants with baseline endothelin-1 levels in higher quartiles had a greater
incidence of CKD in the fully adjusted model (odds ratio for fourth versus first
quartile, 1.81; 95% confidence interval, 1.11 to 2.96; Ptrend=0.04). Endothelin-1
positively associated with all-cause mortality (hazard ratio for fourth versus
first quartile, 1.64; 95% confidence interval, 1.24 to 2.16; Ptrend<0.001). In
conclusion, higher baseline serum endothelin-1 levels associated with incident
CKD and all-cause mortality during follow-up in this general population sample of
blacks.
PMID- 28698271
TI - Mannose-Binding Lectin Levels Could Predict Prognosis in IgA Nephropathy.
AB - IgA nephropathy (IgAN) is characterized by infections followed by episodic gross
hematuria. Deficiency of mannose-binding lectin (MBL) is associated with
recurrent infection in many diseases, but controversy exists regarding the role
of MBL in IgAN. Here, we measured MBL2 variants and MBL levels in 749 patients
with IgAN and 489 healthy controls. Overall, 5.2% (39 of 749) of patients with
IgAN had MBL deficiency (MBL levels <100 ng/ml), among whom LYPB/LYPB and
LXPA/LYPB were the predominant MBL2 haplotypes (82%; 32 of 39). We found a
nonlinear association between MBL levels and renal outcome in IgAN. Patients with
IgAN and MBL deficiency had a higher incidence of prodromic infections and gross
hematuria than those with sufficient MBL levels (100-3540 ng/ml). Moreover, MBL
deficiency independently associated with poor renal outcome in IgAN after
multiple adjustments (hazard ratio, 5.18; 95% confidence interval, 2.50 to 10.72;
P<0.001). Patients with high MBL levels (>3540 ng/ml) had more severe proteinuria
and a higher proportion of crescents, although the association with IgAN
progression did not reach statistical significance after adjustments. In
conclusion, MBL deficiency and MBL excess may both have deleterious effects on
IgAN progression, which suggests that MBL contributes to IgAN pathogenesis
through multiple mechanisms.
PMID- 28698272
TI - Mycobacterium tuberculosis PhoY Proteins Promote Persister Formation by Mediating
Pst/SenX3-RegX3 Phosphate Sensing.
AB - The Mycobacterium tuberculosis phosphate-specific transport (Pst) system controls
gene expression in response to phosphate availability by inhibiting the
activation of the SenX3-RegX3 two-component system under phosphate-rich
conditions, but the mechanism of communication between these systems is unknown.
In Escherichia coli, inhibition of the two-component system PhoR-PhoB under
phosphate-rich conditions requires both the Pst system and PhoU, a putative
adaptor protein. E. coli PhoU is also involved in the formation of persisters, a
subpopulation of phenotypically antibiotic-tolerant bacteria. M. tuberculosis
encodes two PhoU orthologs, PhoY1 and PhoY2. We generated phoY single- and double
deletion mutants and examined the expression of RegX3-regulated genes by
quantitative reverse transcription-PCR (qRT-PCR). Gene expression was increased
only in the DeltaphoY1 DeltaphoY2 double mutant and could be restored to the wild
type level by complementation with either phoY1 or phoY2 or by deletion of regX3
These data suggest that the PhoY proteins function redundantly to inhibit SenX3
RegX3 activation. We analyzed the frequencies of antibiotic-tolerant persister
variants in the phoY mutants using several antibiotic combinations. Persister
frequency was decreased at least 40-fold in the DeltaphoY1 DeltaphoY2 mutant
compared to the frequency in the wild type, and this phenotype was RegX3
dependent. A DeltapstA1 mutant lacking a Pst system transmembrane component
exhibited a similar RegX3-dependent decrease in persister frequency. In aerosol
infected mice, the DeltaphoY1 DeltaphoY2 and DeltapstA1 mutants were more
susceptible to treatment with rifampin but not isoniazid. Our data demonstrate
that disrupting phosphate sensing mediated by the PhoY proteins and the Pst
system enhances the susceptibility of M. tuberculosis to antibiotics both in
vitro and during infection.IMPORTANCE Persister variants, subpopulations of
bacteria that are phenotypically antibiotic tolerant, contribute to the lengthy
treatment times required to cure Mycobacterium tuberculosis infection, but the
molecular mechanisms governing their formation and maintenance are poorly
characterized. Here, we demonstrate that a phosphate-sensing signal transduction
system, comprising the Pst phosphate transporter, the two-component system SenX3
RegX3, and functionally redundant PhoY proteins that mediate signaling between
Pst and SenX3-RegX3, influences persister formation. Activation of RegX3 by
deletion of the phoY genes or a Pst system component resulted in decreased
persister formation in vitro Activated RegX3 also limited persister formation
during growth under phosphate-limiting conditions. Importantly, increased
susceptibility to the front-line drug rifampin was also observed in a mouse
infection model. Thus, the M. tuberculosis phosphate-sensing signal transduction
system contributes to antibiotic tolerance and is a potential target for the
development of novel therapeutics that may shorten the duration of tuberculosis
treatment.
PMID- 28698273
TI - Viral MicroRNAs Repress the Cholesterol Pathway, and 25-Hydroxycholesterol
Inhibits Infection.
AB - From various screens, we found that Kaposi's sarcoma-associated herpesvirus
(KSHV) viral microRNAs (miRNAs) target several enzymes in the
mevalonate/cholesterol pathway. 3-Hydroxy-3-methylglutaryl-coenzyme A (CoA)
synthase 1 (HMGCS1), 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR [a rate
limiting step in the mevalonate pathway]), and farnesyl-diphosphate
farnesyltransferase 1 (FDFT1 [a committed step in the cholesterol branch]) are
repressed by multiple KSHV miRNAs. Transfection of viral miRNA mimics in primary
endothelial cells (human umbilical vein endothelial cells [HUVECs]) is sufficient
to reduce intracellular cholesterol levels; however, small interfering RNAs
(siRNAs) targeting only HMGCS1 did not reduce cholesterol levels. This suggests
that multiple targets are needed to perturb this tightly regulated pathway. We
also report here that cholesterol levels were decreased in de novo-infected
HUVECs after 7 days. This reduction is at least partially due to viral miRNAs,
since the mutant form of KSHV lacking 10 of the 12 miRNA genes had increased
cholesterol compared to wild-type infections. We hypothesized that KSHV is
downregulating cholesterol to suppress the antiviral response by a modified form
of cholesterol, 25-hydroxycholesterol (25HC). We found that the cholesterol 25
hydroxylase (CH25H) gene, which is responsible for generating 25HC, had increased
expression in de novo-infected HUVECs but was strongly suppressed in long-term
latently infected cell lines. We found that 25HC inhibits KSHV infection when
added exogenously prior to de novo infection. In conclusion, we found that
multiple KSHV viral miRNAs target enzymes in the mevalonate pathway to modulate
cholesterol in infected cells during latency. This repression of cholesterol
levels could potentially be beneficial to viral infection by decreasing the
levels of 25HC.IMPORTANCE A subset of viruses express unique microRNAs (miRNAs),
which act like cellular miRNAs to generally repress host gene expression. A
cancer virus, Kaposi's sarcoma-associated herpesvirus (KSHV, or human herpesvirus
8 [HHV-8]), encodes multiple miRNAs that repress gene expression of multiple
enzymes that are important for cholesterol synthesis. In cells with these viral
miRNAs or with natural infection, cholesterol levels are reduced, indicating
these viral miRNAs decrease cholesterol levels. A modified form of cholesterol,
25-hydroxycholesterol, is generated directly from cholesterol. Addition of 25
hydroxycholesterol to primary cells inhibited KSHV infection of cells, suggesting
that viral miRNAs may decrease cholesterol levels to decrease the concentration
of 25-hydroxycholesterol and to promote infection. These results suggest a new
virus-host relationship and indicate a previously unidentified viral strategy to
lower cholesterol levels.
PMID- 28698274
TI - Noroviruses Co-opt the Function of Host Proteins VAPA and VAPB for Replication
via a Phenylalanine-Phenylalanine-Acidic-Tract-Motif Mimic in Nonstructural Viral
Protein NS1/2.
AB - The Norovirus genus contains important human pathogens, but the role of host
pathways in norovirus replication is largely unknown. Murine noroviruses provide
the opportunity to study norovirus replication in cell culture and in small
animals. The human norovirus nonstructural protein NS1/2 interacts with the host
protein VAMP-associated protein A (VAPA), but the significance of the NS1/2-VAPA
interaction is unexplored. Here we report decreased murine norovirus replication
in VAPA- and VAPB-deficient cells. We characterized the role of VAPA in detail.
VAPA was required for the efficiency of a step(s) in the viral replication cycle
after entry of viral RNA into the cytoplasm but before the synthesis of viral
minus-sense RNA. The interaction of VAPA with viral NS1/2 proteins is conserved
between murine and human noroviruses. Murine norovirus NS1/2 directly bound the
major sperm protein (MSP) domain of VAPA through its NS1 domain. Mutations within
NS1 that disrupted interaction with VAPA inhibited viral replication. Structural
analysis revealed that the viral NS1 domain contains a mimic of the phenylalanine
phenylalanine-acidic-tract (FFAT) motif that enables host proteins to bind to the
VAPA MSP domain. The NS1/2-FFAT mimic region interacted with the VAPA-MSP domain
in a manner similar to that seen with bona fide host FFAT motifs. Amino acids in
the FFAT mimic region of the NS1 domain that are important for viral replication
are highly conserved across murine norovirus strains. Thus, VAPA interaction with
a norovirus protein that functionally mimics host FFAT motifs is important for
murine norovirus replication.IMPORTANCE Human noroviruses are a leading cause of
gastroenteritis worldwide, but host factors involved in norovirus replication are
incompletely understood. Murine noroviruses have been studied to define
mechanisms of norovirus replication. Here we defined the importance of the
interaction between the hitherto poorly studied NS1/2 norovirus protein and the
VAPA host protein. The NS1/2-VAPA interaction is conserved between murine and
human noroviruses and was important for early steps in murine norovirus
replication. Using structure-function analysis, we found that NS1/2 contains a
short sequence that molecularly mimics the FFAT motif that is found in multiple
host proteins that bind VAPA. This represents to our knowledge the first example
of functionally important mimicry of a host FFAT motif by a microbial protein.
PMID- 28698275
TI - CRISPR/Cas9 Genome Editing Reveals That the Intron Is Not Essential for var2csa
Gene Activation or Silencing in Plasmodium falciparum.
AB - Plasmodium falciparum relies on monoallelic expression of 1 of 60 var virulence
genes for antigenic variation and host immune evasion. Each var gene contains a
conserved intron which has been implicated in previous studies in both activation
and repression of transcription via several epigenetic mechanisms, including
interaction with the var promoter, production of long noncoding RNAs (lncRNAs),
and localization to repressive perinuclear sites. However, functional studies
have relied primarily on artificial expression constructs. Using the recently
developed P. falciparum clustered regularly interspaced short palindromic repeats
(CRISPR)/Cas9 system, we directly deleted the var2csa P. falciparum 3D7_1200600
(Pf3D7_1200600) endogenous intron, resulting in an intronless var gene in a
natural, marker-free chromosomal context. Deletion of the var2csa intron resulted
in an upregulation of transcription of the var2csa gene in ring-stage parasites
and subsequent expression of the PfEMP1 protein in late-stage parasites. Intron
deletion did not affect the normal temporal regulation and subsequent
transcriptional silencing of the var gene in trophozoites but did result in
increased rates of var gene switching in some mutant clones. Transcriptional
repression of the intronless var2csa gene could be achieved via long-term culture
or panning with the CD36 receptor, after which reactivation was possible with
chondroitin sulfate A (CSA) panning. These data suggest that the var2csa intron
is not required for silencing or activation in ring-stage parasites but point to
a subtle role in regulation of switching within the var gene
family.IMPORTANCEPlasmodium falciparum is the most virulent species of malaria
parasite, causing high rates of morbidity and mortality in those infected.
Chronic infection depends on an immune evasion mechanism termed antigenic
variation, which in turn relies on monoallelic expression of 1 of ~60 var genes.
Understanding antigenic variation and the transcriptional regulation of
monoallelic expression is important for developing drugs and/or vaccines. The var
gene family encodes the antigenic surface proteins that decorate infected
erythrocytes. Until recently, studying the underlying genetic elements that
regulate monoallelic expression in P. falciparum was difficult, and most studies
relied on artificial systems such as episomal reporter genes. Our study was the
first to use CRISPR/Cas9 genome editing for the functional study of an important,
conserved genetic element of var genes-the intron-in an endogenous, episome-free
manner. Our findings shed light on the role of the var gene intron in
transcriptional regulation of monoallelic expression.
PMID- 28698276
TI - A Novel Single-Cell FISH-Flow Assay Identifies Effector Memory CD4+ T cells as a
Major Niche for HIV-1 Transcription in HIV-Infected Patients.
AB - Cells that actively transcribe HIV-1 have been defined as the "active viral
reservoir" in HIV-infected individuals. However, important technical limitations
have precluded the characterization of this specific viral reservoir during both
treated and untreated HIV-1 infections. Here, we used a novel single-cell RNA
fluorescence in situ hybridization-flow cytometry (FISH-flow) assay that requires
only 15 million unfractionated peripheral blood mononuclear cells (PBMCs) to
characterize the specific cell subpopulations that transcribe HIV RNA in
different subsets of CD4+ T cells. In samples from treated and untreated HIV
infected patients, effector memory CD4+ T cells were the main cell population
supporting HIV RNA transcription. The number of cells expressing HIV correlated
with the plasma viral load, intracellular HIV RNA, and proviral DNA quantified by
conventional methods and inversely correlated with the CD4+ T cell count and the
CD4/CD8 ratio. We also found that after ex vivo infection of unstimulated PBMCs,
HIV-infected T cells upregulated the expression of CD32. In addition, this new
methodology detected increased numbers of primary cells expressing viral
transcripts and proteins after ex vivo viral reactivation with latency reversal
agents. This RNA FISH-flow technique allows the identification of the specific
cell subpopulations that support viral transcription in HIV-1-infected
individuals and has the potential to provide important information on the
mechanisms of viral pathogenesis, HIV persistence, and viral
reactivation.IMPORTANCE Persons infected with HIV-1 contain several cellular
viral reservoirs that preclude the complete eradication of the viral infection.
Using a novel methodology, we identified effector memory CD4+ T cells, immune
cells preferentially located in inflamed tissues with potent activity against
pathogens, as the main cells encompassing the transcriptionally active HIV-1
reservoir in patients on antiretroviral therapy. Importantly, the identification
of such cells provides us with an important target for new therapies designed to
target the hidden virus and thus to eliminate the virus from the human body. In
addition, because of its ability to identify cells forming part of the viral
reservoir, the assay used in this study represents an important new tool in the
field of HIV pathogenesis and viral persistence.
PMID- 28698277
TI - Deep-Sea Hydrothermal Vent Viruses Compensate for Microbial Metabolism in Virus
Host Interactions.
AB - Viruses are believed to be responsible for the mortality of host organisms.
However, some recent investigations reveal that viruses may be essential for host
survival. To date, it remains unclear whether viruses are beneficial or harmful
to their hosts. To reveal the roles of viruses in the virus-host interactions,
viromes and microbiomes of sediment samples from three deep-sea hydrothermal
vents were explored in this study. To exclude the influence of exogenous DNAs on
viromes, the virus particles were purified with nuclease (DNase I and RNase A)
treatments and cesium chloride density gradient centrifugation. The metagenomic
analysis of viromes without exogenous DNA contamination and microbiomes of vent
samples indicated that viruses had compensation effects on the metabolisms of
their host microorganisms. Viral genes not only participated in most of the
microbial metabolic pathways but also formed branched pathways in microbial
metabolisms, including pyrimidine metabolism; alanine, aspartate, and glutamate
metabolism; nitrogen metabolism and assimilation pathways of the two-component
system; selenocompound metabolism; aminoacyl-tRNA biosynthesis; and amino sugar
and nucleotide sugar metabolism. As is well known, deep-sea hydrothermal vent
ecosystems exist in relatively isolated environments which are barely influenced
by other ecosystems. The metabolic compensation of hosts mediated by viruses
might represent a very important aspect of virus-host interactions.IMPORTANCE
Viruses are the most abundant biological entities in the oceans and have very
important roles in regulating microbial community structure and biogeochemical
cycles. The relationship between virus and host microbes is broadly thought to be
that of predator and prey. Viruses can lyse host cells to control microbial
population sizes and affect community structures of hosts by killing specific
microbes. However, viruses also influence their hosts through manipulation of
bacterial metabolism. We found that viral genes not only participated in most
microbial metabolic pathways but also formed branched pathways in microbial
metabolisms. The metabolic compensation of hosts mediated by viruses may help
hosts to adapt to extreme environments and may be essential for host survival.
PMID- 28698278
TI - On the Origin of Reverse Transcriptase-Using CRISPR-Cas Systems and Their
Hyperdiverse, Enigmatic Spacer Repertoires.
AB - Cas1 integrase is the key enzyme of the clustered regularly interspaced short
palindromic repeat (CRISPR)-Cas adaptation module that mediates acquisition of
spacers derived from foreign DNA by CRISPR arrays. In diverse bacteria, the cas1
gene is fused (or adjacent) to a gene encoding a reverse transcriptase (RT)
related to group II intron RTs. An RT-Cas1 fusion protein has been recently shown
to enable acquisition of CRISPR spacers from RNA. Phylogenetic analysis of the
CRISPR-associated RTs demonstrates monophyly of the RT-Cas1 fusion, and
coevolution of the RT and Cas1 domains. Nearly all such RTs are present within
type III CRISPR-Cas loci, but their phylogeny does not parallel the CRISPR-Cas
type classification, indicating that RT-Cas1 is an autonomous functional module
that is disseminated by horizontal gene transfer and can function with diverse
type III systems. To compare the sequence pools sampled by RT-Cas1-associated and
RT-lacking CRISPR-Cas systems, we obtained samples of a commercially grown
cyanobacterium-Arthrospira platensis Sequencing of the CRISPR arrays uncovered a
highly diverse population of spacers. Spacer diversity was particularly striking
for the RT-Cas1-containing type III-B system, where no saturation was evident
even with millions of sequences analyzed. In contrast, analysis of the RT-lacking
type III-D system yielded a highly diverse pool but reached a point where fewer
novel spacers were recovered as sequencing depth was increased. Matches could be
identified for a small fraction of the non-RT-Cas1-associated spacers, and for
only a single RT-Cas1-associated spacer. Thus, the principal source(s) of the
spacers, particularly the hypervariable spacer repertoire of the RT-associated
arrays, remains unknown.IMPORTANCE While the majority of CRISPR-Cas immune
systems adapt to foreign genetic elements by capturing segments of invasive DNA,
some systems carry reverse transcriptases (RTs) that enable adaptation to RNA
molecules. From analysis of available bacterial sequence data, we find evidence
that RT-based RNA adaptation machinery has been able to join with CRISPR-Cas
immune systems in many, diverse bacterial species. To investigate whether the
abilities to adapt to DNA and RNA molecules are utilized for defense against
distinct classes of invaders in nature, we sequenced CRISPR arrays from samples
of commercial-scale open-air cultures of Arthrospira platensis, a cyanobacterium
that contains both RT-lacking and RT-containing CRISPR-Cas systems. We uncovered
a diverse pool of naturally occurring immune memories, with the RT-lacking locus
acquiring a number of segments matching known viral or bacterial genes, while the
RT-containing locus has acquired spacers from a distinct sequence pool for which
the source remains enigmatic.
PMID- 28698279
TI - Zika Virus Persistently Infects and Is Basolaterally Released from Primary Human
Brain Microvascular Endothelial Cells.
AB - Zika virus (ZIKV) is a mosquito-borne Flavivirus that has emerged as the cause of
encephalitis and fetal microencephaly in the Americas. ZIKV uniquely persists in
human bodily fluids for up to 6 months, is sexually transmitted, and traverses
the placenta and the blood-brain barrier (BBB) to damage neurons. Cells that
support persistent ZIKV replication and mechanisms by which ZIKV establishes
persistence remain enigmatic but central to ZIKV entry into protected neuronal
compartments. The endothelial cell (EC) lining of capillaries normally constrains
transplacental transmission and forms the BBB, which selectively restricts access
of blood constituents to neurons. We found that ZIKV (strain PRVABC59)
persistently infects and continuously replicates in primary human brain
microvascular ECs (hBMECs), without cytopathology, for >9 days and following
hBMEC passage. ZIKV did not permeabilize hBMECs but was released basolaterally
from polarized hBMECs, suggesting a direct mechanism for ZIKV to cross the BBB.
ZIKV-infected hBMECs were rapidly resistant to alpha interferon (IFN-alpha) and
transiently induced, but failed to secrete, IFN-beta and IFN-lambda. Global
transcriptome analysis determined that ZIKV constitutively induced IFN regulatory
factor 7 (IRF7), IRF9, and IFN-stimulated genes (ISGs) 1 to 9 days postinfection,
despite persistently replicating in hBMECs. ZIKV constitutively induced ISG15,
HERC5, and USP18, which are linked to hepatitis C virus (HCV) persistence and IFN
regulation, chemokine CCL5, which is associated with immunopathogenesis, as well
as cell survival factors. Our results reveal that hBMECs act as a reservoir of
persistent ZIKV replication, suggest routes for ZIKV to cross hBMECs into
neuronal compartments, and define novel mechanisms of ZIKV persistence that can
be targeted to restrict ZIKV spread.IMPORTANCE ZIKV persists in patients,
crossing placental and neuronal barriers, damaging neurons, and causing fetal
microencephaly. We found that ZIKV persistently infects brain endothelial cells
that normally protect neurons from viral exposure. hBMECs are not damaged by ZIKV
infection and, analogous to persistent HCV infection, ZIKV constitutively induces
and evades antiviral ISG and IFN responses to continuously replicate in hBMECs.
As a result, hBMECs provide a protective niche for systemic ZIKV spread and a
viral reservoir localized in the normally protective blood-brain barrier.
Consistent with the spread of ZIKV into neuronal compartments, ZIKV was released
basolaterally from hBMECs. Our findings define hBMEC responses that contribute to
persistent ZIKV infection and potential targets for clearing ZIKV infections from
hBMECs. These results further suggest roles for additional ZIKV-infected ECs to
facilitate viral spread and persistence in the protected placental, retinal, and
testicular compartments.
PMID- 28698280
TI - Glycemic control after metabolic surgery: a Granger causality and graph analysis.
AB - The purpose of this study was to examine the contribution of nonesterified fatty
acids (NEFA) and incretin to insulin resistance and diabetes amelioration after
malabsorptive metabolic surgery that induces steatorrhea. In fact, NEFA infusion
reduces glucose-stimulated insulin secretion, and high-fat diets predict diabetes
development. Six healthy controls, 11 obese subjects, and 10 type 2 diabetic
(T2D) subjects were studied before and 1 mo after biliopancreatic diversion
(BPD). Twenty-four-hour plasma glucose, NEFA, insulin, C-peptide, glucagon-like
peptide-1 (GLP-1), and gastric inhibitory polypeptide (GIP) time courses were
obtained and analyzed by Granger causality and graph analyses. Insulin
sensitivity and secretion were computed by the oral glucose minimal model. Before
metabolic surgery, NEFA levels had the strongest influence on the other variables
in both obese and T2D subjects. After surgery, GLP-1 and C-peptide levels
controlled the system in obese and T2D subjects. Twenty-four-hour GIP levels were
markedly reduced after BPD. Finally, not only did GLP-1 levels play a central
role, but also insulin and C-peptide levels had a comparable relevance in the
network of healthy controls. After BPD, insulin sensitivity was completely
normalized in both obese and T2D individuals. Increased 24-h GLP-1 circulating
levels positively influenced glucose homeostasis in both obese and T2D subjects
who underwent a malabsorptive bariatric operation. In the latter, the reduction
of plasma GIP levels also contributed to the improvement of glucose metabolism.
It is possible that the combination of a pharmaceutical treatment reducing GIP
and increasing GLP-1 plasma levels will contribute to better glycemic control in
T2D. The application of Granger causality and graph analyses sheds new light on
the pathophysiology of metabolic surgery.
PMID- 28698281
TI - MiR-27b augments bone marrow progenitor cell survival via suppressing the
mitochondrial apoptotic pathway in Type 2 diabetes.
AB - Bone marrow-derived progenitor cells (BMPCs) are potential candidates for
autologous cell therapy in tissue repair and regeneration because of their high
angiogenic potential. However, increased progenitor cell apoptosis in diabetes
directly limits their success in the clinic. MicroRNAs are endogenous noncoding
RNAs that regulate gene expression at the posttranscriptional level, but their
roles in BMPC-mediated angiogenesis are incompletely understood. In the present
study, we tested the hypothesis that the proangiogenic miR-27b inhibits BMPC
apoptosis in Type 2 diabetes. Bone marrow-derived EPCs from adult male Type 2
diabetic db/db mice and their normal littermates db/+ mice were used. MiR-27b
expression (real-time PCR) in EPCs was decreased after 24 h of exposure to
methylglyoxal (MGO) or oxidized low-density lipoprotein but not high glucose,
advanced glycation end products, the reactive oxygen species generator LY83583,
or H2O2 The increase in BMPC apoptosis in the diabetic mice was rescued following
transfection with a miR-27b mimic, and the increased apoptosis induced by MGO was
also rescued by the miR-27b mimic. p53 protein expression and the Bax/Bcl-2 ratio
in EPCs (Western blot analyses) were significantly higher in db/db mice, both of
which were suppressed by miR-27b. Furthermore, mitochondrial respiration, as
measured by oxygen consumption rate, was enhanced by miR-27b in diabetic BMPCs,
with concomitant decrease of mitochondrial Bax/Bcl-2 ratio. The 3' UTR binding
assays revealed that both Bax, and its activator RUNX1, were direct targets of
miR-27b, suggesting that miR-27b inhibits Bax expression in both direct and
indirect manners. miR-27b prevents EPC apoptosis in Type 2 diabetic mice, at
least in part, by suppressing p53 and the Bax/Bcl-2 ratio. These findings may
provide a mechanistic basis for rescuing BMPC dysfunction in diabetes for
successful autologous cell therapy.
PMID- 28698282
TI - Circulating sex steroids coregulate adipose tissue immune cell populations in
healthy men.
AB - Male hypogonadism results in changes in body composition characterized by
increases in fat mass. Resident immune cells influence energy metabolism in
adipose tissue and could promote increased adiposity through paracrine effects.
We hypothesized that manipulation of circulating sex steroid levels in healthy
men would alter adipose tissue immune cell populations. Subjects (n = 44 men, 19
55 yr of age) received 4 wk of treatment with the gonadotropin-releasing hormone
receptor antagonist acyline with daily administration of 1) placebo gel, 2) 1.25
g testosterone gel (1.62%), 3) 5 g testosterone gel, or 4) 5 g testosterone gel
with an aromatase inhibitor. Subcutaneous adipose tissue biopsies were performed
at baseline and end-of-treatment, and adipose tissue immune cells, gene
expression, and intra-adipose estrogen levels were quantified. Change in serum
total testosterone level correlated inversely with change in the number of CD3+
(beta = -0.36, P = 0.04), CD4+ (beta = -0.34, P = 0.04), and CD8+ (beta = -0.33,
P = 0.05) T cells within adipose tissue. Change in serum 17beta-estradiol level
correlated inversely with change in the number of adipose tissue macrophages
(ATMs) (beta = -0.34, P = 0.05). A negative association also was found between
change in serum testosterone and change in CD11c+ ATMs (beta = -0.41, P = 0.01).
Overall, sex steroid deprivation was associated with increases in adipose tissue
T cells and ATMs. No associations were found between changes in serum sex steroid
levels and changes in adipose tissue gene expression. Circulating sex steroid
levels may regulate adipose tissue immune cell populations. These exploratory
findings highlight a possible novel mechanism that could contribute to increased
metabolic risk in hypogonadal men.
PMID- 28698283
TI - Long-term rates of mitochondrial protein synthesis are increased in mouse
skeletal muscle with high-fat feeding regardless of insulin-sensitizing
treatment.
AB - Skeletal muscle mitochondrial protein synthesis is regulated in part by insulin.
The development of insulin resistance with diet-induced obesity may therefore
contribute to impairments to protein synthesis and decreased mitochondrial
respiration. Yet the impact of diet-induced obesity and insulin resistance on
mitochondrial energetics is controversial, with reports varying from decreases to
increases in mitochondrial respiration. We investigated the impact of changes in
insulin sensitivity on long-term rates of mitochondrial protein synthesis as a
mechanism for changes to mitochondrial respiration in skeletal muscle. Insulin
resistance was induced in C57BL/6J mice using 4 wk of a high-fat compared with a
low-fat diet. For 8 additional weeks, diets were enriched with pioglitazone to
restore insulin sensitivity compared with nonenriched control low-fat or high-fat
diets. Skeletal muscle mitochondrial protein synthesis was measured using
deuterium oxide labeling during weeks 10-12 High-resolution respirometry was
performed using palmitoyl-l-carnitine, glutamate+malate, and
glutamate+malate+succinate as substrates for mitochondria isolated from
quadriceps. Mitochondrial protein synthesis and palmitoyl- l-carnitine oxidation
were increased in mice consuming a high-fat diet, regardless of differences in
insulin sensitivity with pioglitazone treatment. There was no effect of diet or
pioglitazone treatment on ADP-stimulated respiration or H2O2 emission using
glutamate+malate or glutamate+malate+succinate. The results demonstrate no
impairments to mitochondrial protein synthesis or respiration following induction
of insulin resistance. Instead, mitochondrial protein synthesis was increased
with a high-fat diet and may contribute to remodeling of the mitochondria to
increase lipid oxidation capacity. Mitochondrial adaptations with a high-fat diet
appear driven by nutrient availability, not intrinsic defects that contribute to
insulin resistance.
PMID- 28698284
TI - Breaching peripheral tolerance promotes the production of HIV-1-neutralizing
antibodies.
AB - A subset of characterized HIV-1 broadly neutralizing antibodies (bnAbs) are
polyreactive with additional specificities for self-antigens and it has been
proposed immunological tolerance may present a barrier to their participation in
protective humoral immunity. We address this hypothesis by immunizing autoimmune
prone mice with HIV-1 Envelope (Env) and characterizing the primary antibody
response for HIV-1 neutralization. We find autoimmune mice generate neutralizing
antibody responses to tier 2 HIV-1 strains with alum treatment alone in the
absence of Env. Importantly, experimentally breaching immunological tolerance in
wild-type mice also leads to the production of tier 2 HIV-1-neutralizing
antibodies, which increase in breadth and potency following Env immunization. In
both genetically prone and experimentally induced mouse models of autoimmunity,
increased serum levels of IgM anti-histone H2A autoantibodies significantly
correlated with tier 2 HIV-1 neutralization, and anti-H2A antibody clones were
found to neutralize HIV-1. These data demonstrate that breaching peripheral
tolerance permits a cross-reactive HIV-1 autoantibody response able to neutralize
HIV-1.
PMID- 28698285
TI - Therapeutic antibody targeting of Notch3 signaling prevents mural cell loss in
CADASIL.
AB - Cerebral autosomal-dominant arteriopathy with subcortical infarcts and
leukoencephalopathy (CADASIL) is a neurological syndrome characterized by small
vessel disease (SVD), stroke, and vascular cognitive impairment and dementia
caused by mutations in NOTCH3 No therapies are available for this condition. Loss
of mural cells, which encompass pericytes and vascular smooth muscle cells, is a
hallmark of CADASIL and other SVDs, including diabetic retinopathy, resulting in
vascular instability. Here, we showed that Notch3 signaling is both necessary and
sufficient to support mural cell coverage in arteries using genetic rescue in
Notch3 knockout mice. Furthermore, we show that systemic administration of an
agonist Notch3 antibody prevents mural cell loss and modifies plasma proteins
associated with Notch3 activity, including endostatin/collagen 18alpha1 and
Notch3 extracellular domain in mice with the C455R mutation, a CADASIL variant
associated with Notch3 loss of function. These findings open opportunities for
the treatment of CADASIL and other SVDs by modulating Notch3 signaling.
PMID- 28698286
TI - Tissue microenvironment dictates the fate and tumor-suppressive function of type
3 ILCs.
AB - Innate lymphoid cells (ILCs) have been classified into "functional subsets"
according to their transcription factor and cytokine profiles. Although
cytokines, such as IL-12 and IL-23, have been shown to shape plasticity of ILCs,
little is known about how the tissue microenvironment influences the plasticity,
phenotype, and function of these cells. Here, we show clearly demarcated tissue
specifications of Rorc-dependent ILCs across lymphoid and nonlymphoid organs.
Although intestinal Rorc fate map-positive (Rorcfm+) ILCs show a clear ILC3
phenotype, lymphoid tissue-derived Rorcfm+ ILCs acquire an natural killer (NK)
cell/ILC1-like phenotype. By adoptively transferring Rorcfm+ ILCs into recipient
mice, we show that ILCs distribute among various organs and phenotypically adapt
to the tissue environment they invade. When investigating their functional
properties, we found that only lymphoid-tissue resident Rorcfm+ ILCs can suppress
tumor growth, whereas intestinal Rorcfm- ILC1s or NK cells fail to inhibit tumor
progression. We thus propose that the tissue microenvironment, combined with
ontogeny, provides the specific function, whereas the phenotype is insufficient
to predict the functional properties of ILCs.
PMID- 28698287
TI - Blimp-1-dependent and -independent natural antibody production by B-1 and B-1
derived plasma cells.
AB - Natural antibodies contribute to tissue homeostasis and protect against
infections. They are secreted constitutively without external antigenic
stimulation. The differentiation state and regulatory pathways that enable
continuous natural antibody production by B-1 cells, the main cellular source in
mice, remain incompletely understood. Here we demonstrate that natural IgM
secreting B-1 cells in the spleen and bone marrow are heterogeneous, consisting
of (a) terminally differentiated B-1-derived plasma cells expressing the
transcriptional regulator of differentiation, Blimp-1, (b) Blimp-1+, and (c)
Blimp-1neg phenotypic B-1 cells. Blimp-1neg IgM-secreting B-1 cells are not
simply intermediates of cellular differentiation. Instead, they secrete similar
amounts of IgM in wild-type and Blimp-1-deficient (PRDM-1DeltaEx1A) mice. Blimp
1neg B-1 cells are also a major source of IgG3. Consequently, deletion of Blimp-1
changes neither serum IgG3 levels nor the amount of IgG3 secreted per cell. Thus,
the pool of natural antibody-secreting B-1 cells is heterogeneous and contains a
distinct subset of cells that do not use Blimp-1 for initiation or maximal
antibody secretion.
PMID- 28698288
TI - Impact of Forward Stroke Volume Response on Clinical and Structural Outcomes
After Percutaneous Mitral Valve Repair With MitraClip.
AB - BACKGROUND: An increase of systolic forward flow was frequently observed after
successful MitraClip implantation in patients with significant mitral
regurgitation. However, the impact of systolic forward flow improvement on post
MitraClip outcomes remains unknown. METHODS AND RESULTS: Study population
included 160 patients who underwent successful MitraClip implantation. The
systolic forward flow was noninvasively calculated as the forward stroke volume
(FSV) at baseline before the MitraClip procedure and before discharge with pulse
wave Doppler using transthoracic echocardiography. The optimal threshold of
discharge/baseline FSV ratio for 3-year all-cause death was assessed. The best
cutoff ratio was 1.09 (9% FSV increase from baseline, P=0.006). The FSV
responders were defined as those with >9% increase of FSV from baseline (n=93).
From discharge to 12-month follow-up, a significant reduction of LV end-diastolic
and end-systolic volumes was observed in the responders, whereas no significant
change was observed in the nonresponders. Furthermore, the proportion of New York
Heart Association functional class III/IV was significantly lower in the
responders at 12 months (2.9% versus 14.6%; P=0.03). Among patients with
estimated glomerular filtration rate <60 mL/min per 1.73 m2, estimated glomerular
filtration rate was significantly improved at 12 months only in the responders.
All-cause mortality at 3 years was significantly lower in the responders than in
the nonresponders (17.6% versus 42.3%; P=0.002). Multivariable logistic analysis
identified higher baseline FSV, less mitral regurgitation severity, and
functional mitral regurgitation as independent predictors of the nonresponders.
CONCLUSIONS: FSV increase after MitraClip implantation was associated with more
favorable clinical and anatomic outcomes. Severity and pathogenesis of mitral
regurgitation and pre-MitraClip FSV predicted postprocedural FSV response.
PMID- 28698289
TI - Mechanism and Implications of the Tricuspid Regurgitation: From the
Pathophysiology to the Current and Future Therapeutic Options.
AB - The tricuspid valve was virtually ignored for a long time in the past. However,
significant tricuspid regurgitation (TR) often accompanies left-side heart valve
pathology and does not always reverse with its correction. If left untreated, TR
can progress and result in progressive right ventricular failure. Current
guideline recommendations still hold minor differences. Nevertheless, there is a
consensus to operate on patients with severe TR undergoing left-sided valve
surgery (class I) or those with mild to moderate TR with a dilated annulus (>=40
or >=21 mm2, Class IIa). However, in case of the primary TR, surgical options is
limited by a relatively high risk of mortality and morbidity. For these patients,
new percutaneous approaches are becoming available but no long-term data are
still available. In this review, we provide a comprehensive overview of the
epidemiological and pathophysiological aspects of TR, and the current and future
directions of therapy.
PMID- 28698290
TI - Clinical and Echocardiographic Outcomes Following Permanent Pacemaker
Implantation After Transcatheter Aortic Valve Replacement: Meta-Analysis and Meta
Regression.
AB - BACKGROUND: Transcatheter aortic valve replacement has become the procedure of
choice for inoperable, high-risk, and many intermediate-risk patients with aortic
stenosis. Conduction abnormalities are a common finding after transcatheter
aortic valve replacement and often result in permanent pacemaker (PPM)
implantation. Data pertaining to the clinical impact of PPM implantation are
controversial. We used meta-analysis techniques to summarize the effect of PPM
implantation on clinical and echocardiographic outcomes after transcatheter
aortic valve replacement. METHODS AND RESULTS: Data were summarized as Mantel
Haenszel relative risk (RR) and 95% confidence intervals (CIs) for dichotomous
variables and as standardized mean difference and 95% CI for continuous variables
We used the Higgins I2 statistic to evaluate heterogeneity. We found that
patients with and without PPM have similar all-cause mortality (RR, 0.85; 95% CI,
0.70-1.03), cardiovascular mortality (RR, 0.84; 95% CI, 0.59-1.18), myocardial
infarction (RR, 0.47; 95% CI, 0.20-1.11), and stroke (RR, 1.26; 95% CI, 0.70
2.26) at 30 days. The groups were also comparable in all-cause mortality (RR,
1.03; 95% CI, 0.92-1.16), cardiovascular mortality (RR, 0.69; 95% CI, 0.39-1.24),
myocardial infarction (RR, 0.58; 95% CI, 0.30-1.13), and stroke (RR, 0.70; 95%
CI, 0.47-1.04) at 1 year. We observed that the improvement in left ventricular
ejection fraction was significantly greater in the patients without PPM
(standardized mean difference, 0.22; 95% CI, 0.12-0.32). CONCLUSIONS: PPM
implantation is not associated with increased risk of all-cause mortality,
cardiovascular mortality, stroke, or myocardial infarction both at short- and
long-term follow-up. However, PPM is associated with impaired left ventricular
ejection fraction recovery post-transcatheter aortic valve replacement.
PMID- 28698291
TI - Bioprosthetic Valve Fracture Improves the Hemodynamic Results of Valve-in-Valve
Transcatheter Aortic Valve Replacement.
AB - BACKGROUND: Valve-in-valve (VIV) transcatheter aortic valve replacement (TAVR)
may be less effective in small surgical valves because of patient/prosthesis
mismatch. Bioprosthetic valve fracture (BVF) using a high-pressure balloon can be
performed to facilitate VIV TAVR. METHODS AND RESULTS: We report data from 20
consecutive clinical cases in which BVF was successfully performed before or
after VIV TAVR by inflation of a high-pressure balloon positioned across the
valve ring during rapid ventricular pacing. Hemodynamic measurements and
calculation of the valve effective orifice area were performed at baseline,
immediately after VIV TAVR, and after BVF. BVF was successfully performed in 20
patients undergoing VIV TAVR with balloon-expandable (n=8) or self-expanding
(n=12) transcatheter valves in Mitroflow, Carpentier-Edwards Perimount, Magna and
Magna Ease, Biocor Epic and Biocor Epic Supra, and Mosaic surgical valves.
Successful fracture was noted fluoroscopically when the waist of the balloon
released and by a sudden drop in inflation pressure, often accompanied by an
audible snap. BVF resulted in a reduction in the mean transvalvular gradient
(from 20.5+/-7.4 to 6.7+/-3.7 mm Hg, P<0.001) and an increase in valve effective
orifice area (from 1.0+/-0.4 to 1.8+/-0.6 cm2, P<0.001). No procedural
complications were reported. CONCLUSIONS: BVF can be performed safely in small
surgical valves to facilitate VIV TAVR with either balloon-expandable or self
expanding transcatheter valves and results in reduced residual transvalvular
gradients and increased valve effective orifice area.
PMID- 28698292
TI - Optical Coherence Tomography Findings in Patients With Recanalized Coronary
Thrombi Treated With Bioresorbable Vascular Scaffolds.
PMID- 28698294
TI - When Device Failure Translates to Therapeutic Efficacy: Intentional Fracture of
Bioprosthetic Valve Rings as an Adjunctive Technique in Transcatheter Valve-in
Valve Replacement.
PMID- 28698293
TI - The Conundrum of Permanent Pacemaker Implantation After Transcatheter Aortic
Valve Implantation.
PMID- 28698295
TI - GP leaders ballot profession on mass list closure.
PMID- 28698296
TI - PRKCI promotes immune suppression in ovarian cancer.
AB - A key feature of high-grade serous ovarian carcinoma (HGSOC) is frequent
amplification of the 3q26 locus harboring PRKC-iota (PRKCI). Here, we show that
PRKCI is also expressed in early fallopian tube lesions, called serous tubal
intraepithelial carcinoma. Transgenic mouse studies establish PRKCI as an ovarian
cancer-specific oncogene. Mechanistically, we show that the oncogenic activity of
PRKCI relates in part to the up-regulation of TNFalpha to promote an immune
suppressive tumor microenvironment characterized by an abundance of myeloid
derived suppressor cells and inhibition of cytotoxic T-cell infiltration.
Furthermore, system-level and functional analyses identify YAP1 as a downstream
effector in tumor progression. In human ovarian cancers, high PRKCI expression
also correlates with high expression of TNFalpha and YAP1 and low infiltration of
cytotoxic T cells. The PRKCI-YAP1 regulation of the tumor immunity provides a
therapeutic strategy for highly lethal ovarian cancer.
PMID- 28698297
TI - Disrupted prenatal RNA processing and myogenesis in congenital myotonic
dystrophy.
AB - Myotonic dystrophy type 1 (DM1) is a CTG microsatellite expansion (CTGexp)
disorder caused by expression of CUGexp RNAs. These mutant RNAs alter the
activities of RNA processing factors, including MBNL proteins, leading to re
expression of fetal isoforms in adult tissues and DM1 pathology. While this
pathogenesis model accounts for adult-onset disease, the molecular basis of
congenital DM (CDM) is unknown. Here, we test the hypothesis that disruption of
developmentally regulated RNA alternative processing pathways contributes to CDM
disease. We identify prominent alternative splicing and polyadenylation
abnormalities in infant CDM muscle, and, although most are also misregulated in
adult-onset DM1, dysregulation is significantly more severe in CDM. Furthermore,
analysis of alternative splicing during human myogenesis reveals that CDM
relevant exons undergo prenatal RNA isoform transitions and are predicted to be
disrupted by CUGexp-associated mechanisms in utero. To test this possibility and
the contribution of MBNLs to CDM pathogenesis, we generated mouse Mbnl double
(Mbnl1; Mbnl2) and triple (Mbnl1; Mbnl2; Mbnl3) muscle-specific knockout models
that recapitulate the congenital myopathy, gene expression, and spliceopathy
defects characteristic of CDM. This study demonstrates that RNA misprocessing is
a major pathogenic factor in CDM and provides novel mouse models to further
examine roles for cotranscriptional/post-transcriptional gene regulation during
development.
PMID- 28698298
TI - GIGYF1/2 proteins use auxiliary sequences to selectively bind to 4EHP and repress
target mRNA expression.
AB - The eIF4E homologous protein (4EHP) is thought to repress translation by
competing with eIF4E for binding to the 5' cap structure of specific mRNAs to
which it is recruited through interactions with various proteins, including the
GRB10-interacting GYF (glycine-tyrosine-phenylalanine domain) proteins 1 and 2
(GIGYF1/2). Despite its similarity to eIF4E, 4EHP does not interact with eIF4G
and therefore fails to initiate translation. In contrast to eIF4G, GIGYF1/2 bind
selectively to 4EHP but not eIF4E. Here, we present crystal structures of the
4EHP-binding regions of GIGYF1 and GIGYF2 in complex with 4EHP, which reveal the
molecular basis for the selectivity of the GIGYF1/2 proteins for 4EHP.
Complementation assays in a GIGYF1/2-null cell line using structure-based mutants
indicate that 4EHP requires interactions with GIGYF1/2 to down-regulate target
mRNA expression. Our studies provide structural insights into the assembly of
4EHP-GIGYF1/2 repressor complexes and reveal that rather than merely facilitating
4EHP recruitment to transcripts, GIGYF1/2 proteins are required for repressive
activity.
PMID- 28698299
TI - Neat1 is a p53-inducible lincRNA essential for transformation suppression.
AB - The p53 gene is mutated in over half of all cancers, reflecting its critical role
as a tumor suppressor. Although p53 is a transcriptional activator that induces
myriad target genes, those p53-inducible genes most critical for tumor
suppression remain elusive. Here, we leveraged p53 ChIP-seq (chromatin
immunoprecipitation [ChIP] combined with high-throughput sequencing) and RNA-seq
(RNA sequencing) data sets to identify new p53 target genes, focusing on the
noncoding genome. We identify Neat1, a noncoding RNA (ncRNA) constituent of
paraspeckles, as a p53 target gene broadly induced by mouse and human p53 in
different cell types and by diverse stress signals. Using fibroblasts derived
from Neat1-/- mice, we examined the functional role of Neat1 in the p53 pathway.
We found that Neat1 is dispensable for cell cycle arrest and apoptosis in
response to genotoxic stress. In sharp contrast, Neat1 plays a crucial role in
suppressing transformation in response to oncogenic signals. Neat1 deficiency
enhances transformation in oncogene-expressing fibroblasts and promotes the
development of premalignant pancreatic intraepithelial neoplasias (PanINs) and
cystic lesions in KrasG12D-expressing mice. Neat1 loss provokes global changes in
gene expression, suggesting a mechanism by which its deficiency promotes
neoplasia. Collectively, these findings identify Neat1 as a p53-regulated large
intergenic ncRNA (lincRNA) with a key role in suppressing transformation and
cancer initiation, providing fundamental new insight into p53-mediated tumor
suppression.
PMID- 28698300
TI - Kinetochores accelerate or delay APC/C activation by directing Cdc20 to opposing
fates.
AB - Mitotic duration is determined by activation of the anaphase-promoting
complex/cyclosome (APC/C) bound to its coactivator, Cdc20. Kinetochores, the
microtubule-interacting machines on chromosomes, restrain mitotic exit when not
attached to spindle microtubules by generating a Cdc20-containing complex that
inhibits the APC/C. Here, we show that flux of Cdc20 through kinetochores also
accelerates mitotic exit by promoting its dephosphorylation by kinetochore
localized protein phosphatase 1, which allows Cdc20 to activate the APC/C. Both
APC/C activation and inhibition depend on Cdc20 fluxing through the same binding
site at kinetochores. The microtubule attachment status of kinetochores therefore
optimizes mitotic duration by controlling the balance between opposing Cdc20
fates.
PMID- 28698301
TI - Prdm16 is required for the maintenance of neural stem cells in the postnatal
forebrain and their differentiation into ependymal cells.
AB - We and others showed previously that PR domain-containing 16 (Prdm16) is a
transcriptional regulator required for stem cell function in multiple fetal and
neonatal tissues, including the nervous system. However, Prdm16 germline knockout
mice died neonatally, preventing us from testing whether Prdm16 is also required
for adult stem cell function. Here we demonstrate that Prdm16 is required for
neural stem cell maintenance and neurogenesis in the adult lateral ventricle
subventricular zone and dentate gyrus. We also discovered that Prdm16 is required
for the formation of ciliated ependymal cells in the lateral ventricle.
Conditional Prdm16 deletion during fetal development using Nestin-Cre prevented
the formation of ependymal cells, disrupting cerebrospinal fluid flow and causing
hydrocephalus. Postnatal Prdm16 deletion using Nestin-CreERT2 did not cause
hydrocephalus or prevent the formation of ciliated ependymal cells but caused
defects in their differentiation. Prdm16 was required in neural stem/progenitor
cells for the expression of Foxj1, a transcription factor that promotes ependymal
cell differentiation. These studies show that Prdm16 is required for adult neural
stem cell maintenance and neurogenesis as well as the formation of ependymal
cells.
PMID- 28698302
TI - Heme Modification Contributes to the Mechanism-Based Inactivation of Human
Cytochrome P450 2J2 by Two Terminal Acetylenic Compounds.
AB - The mechanism-based inactivation of human CYP2J2 by three terminal acetylenic
compounds: N-(methylsulfonyl)-6-(2-propargyloxyphenyl)hexanamide (MS), 17
octadecynoic acid (OD), and danazol (DZ) was investigated. The loss of
hydroxyebastine (OHEB) carboxylation activity in a reconstituted system was time-
and concentration-dependent and required NADPH for MS and OD, but not DZ. The
kinetic constants for the mechanism-based inactivation of OHEB carboxylation
activity were: KI of 6.1 MUM and kinact of 0.22 min-1 for MS and KI of 2.5 MUM
and kinact of 0.05 min-1 for OD. The partition ratios for MS and OD were ~10 and
~20, respectively. Inactivation of CYP2J2 by MS or OD resulted in a loss of the
native heme spectrum and a similar decrease in the reduced CO difference
spectrum. A heme adduct was observed in the MS-inactivated CYP2J2. The possible
reactive metabolite which covalently modified the prosthetic heme was
characterized by analysis of the glutathione conjugates formed by MS or OD
following oxygenation of the ethynyl moiety. Liquid chromatography-mass
spectrometry showed that inactivation by MS or OD did not lead to modification of
apoprotein. Interaction of CYP2J2 with DZ produced a type II binding spectrum
with a Ks of 2.8 MUM and the IC50 for loss of OHEB carboxylation activity was
0.18 MUM. In conclusion, heme modification by MS and OD was responsible for the
mechanism-based inactivation of CYP2J2. The results suggest that the ethynyl
moiety of MS and OD faces the heme iron, whereas the isoxazole ring of DZ is
preferentially oriented toward the heme iron of CYP2J2.
PMID- 28698303
TI - Evaluation of expression and glycosylation status of UGT1A10 in Supersomes and
intestinal epithelial cells with a novel specific UGT1A10 monoclonal antibody.
AB - UDP-Glucuronosyltransferases (UGTs) are major phase II drug-metabolizing enzymes.
Each member of the UGT family exhibits a unique but occasionally overlapping
substrate specificity and tissue-specific expression pattern. Earlier studies
have reported that human UGT1A10 is expressed in the gastrointestinal tract at
the mRNA level, but the evaluation at the protein level, especially tissue or
cellular localization, has lagged behind because of the lack of a specific
antibody. In this study, we prepared a monoclonal antibody to UGT1A10 to
elucidate the tissue/cellular distribution and interindividual variability of
UGT1A10 protein expression. Western blot analysis revealed that the prepared
antibody does not cross-react with any other human UGTs. Using this specific
antibody, we observed that UGT1A10 protein is expressed in the small intestine
but not in the liver or kidney. Immunohistochemical analysis revealed the
expression of UGT1A10 protein in epithelial cells of the crypts and villi of the
duodenum. In the small intestine microsomes from six individuals, the UGT1A10
protein levels exhibited 16-fold variability. Dopamine 3- and 4-glucuronidation,
which is mainly catalyzed by UGT1A10 and by other UGT isoforms marginally,
exhibited 50- to 65-fold variability, and they were not correlated with the
UGT1A10 protein levels. Interestingly, the enzymatic activities of recombinant
UGT1A10 in insect cells that were normalized to the UGT1A10 protein level were
markedly lower than those in pooled human small intestine microsomes. Thus, the
UGT1A10 antibody we generated made it possible to investigate the tissue/cellular
distribution and interindividual variability of UGT1A10 protein expression for
understanding the pharmacological and toxicological role of UGT1A10.
PMID- 28698304
TI - Prediction of Clinically Relevant Herb-Drug Clearance Interactions Using Sandwich
Cultured Human Hepatocytes: Schisandra spp. Case Study.
AB - The Schisandraceae family is reported to have a range of pharmacological
activities, including anti-inflammatory effects. As with all herbal preparations,
extracts of Schisandra species are mixtures composed of >50 lignans, especially
schizandrins, deoxyschizandrins, and gomisins. In China, Schisandra sphenanthera
extract (SSE) is often coadministered with immunosuppressant treatment of
transplant recipients. In cases of coadministration, the potential for herb-drug
interactions (HDIs) increases. Clinical studies have been used to assess HDI
potential of SSE. Results demonstrated that chronic SSE administration reduced
midazolam (MDZ) clearance by 52% in healthy volunteers. Although clinical studies
are definitive and considered the "gold standard," these studies are impractical
for routine HDI assessments. Alternatively, in vitro strategies can be used to
reduce the need for clinical studies. Transporter-certified sandwich-cultured
human hepatocytes (SCHHs) provide a fully integrated hepatic cell system that
maintains drug clearance pathways (metabolism and transport) and key regulatory
pathways constitutive active/androstane receptor and pregnane X receptor
(CAR/PXR) necessary for quantitative assessment of HDI potential. Mechanistic
studies conducted in SCHHs demonstrated that SSE and the more commonly used
dietary supplement Schisandra chinensis extract (SCE) inhibited CYP3A4/5-mediated
metabolism and induced CYP3A4 mRNA in a dose-dependent manner. SSE and SCE
reduced MDZ clearance to 0.577- and 0.599-fold of solvent control, respectively,
in chronically exposed SCHHs. These in vitro results agreed with SSE clinical
findings and predicted a similar in vivo HDI effect with SCE exposure. These
findings support the use of an SCHH system that maintains transport, metabolic,
and regulatory functionality for routine HDI assessments to predict clinically
relevant clearance interactions.
PMID- 28698305
TI - Periodontitis: a global disease and the primary care provider's role.
AB - Individuals who regularly visit a primary care provider (PCP) may not see a
dentist, creating opportunities for PCPs to improve oral health. However, a lack
of expertise among PCPs may limit their impact to improve public oral health.
Using a non-systematic literature review, this article summarises the relevant
literature about periodontitis. Periodontitis affects 10% to -15% of the world's
population. Caused by bacterial inflammation in gingival pockets, periodontal
disease can destroy tissues surrounding the teeth. Factors linked to periodontal
disease include diabetes, atherosclerosis and smoking. Good oral hygiene is
important for both prevention and treatment. Mechanical removal of gingival
irritants by scaling and root planing combined with adjunctive antimicrobial
therapy are first-line treatment options. Surgery is indicated when healthy
levels of gingival tissue are not attained from first-line treatments. By
understanding the fundamentals of periodontitis the primary care provider can
educate patients, promote healthy oral health behaviours and appropriately refer
patients with signs and symptoms of periodontal disease.
PMID- 28698306
TI - David Oliver: Leaving medicine--is the grass always greener?
PMID- 28698307
TI - Origins of mtDNA mutations in ageing.
AB - MtDNA mutations are one of the hallmarks of ageing and age-related diseases. It
is well established that somatic point mutations accumulate in mtDNA of multiple
organs and tissues with increasing age and heteroplasmy is universal in mammals.
However, the origin of these mutations remains controversial. The long-lasting
hypothesis stating that mtDNA mutations emanate from oxidative damage via a self
perpetuating mechanism has been extensively challenged in recent years. Contrary
to this initial ascertainment, mtDNA appears to be well protected from action of
reactive oxygen species (ROS) through robust protein coating and
endomitochondrial microcompartmentalization. Extensive development of scrupulous
high-throughput DNA sequencing methods suggests that an imperfect replication
process, rather than oxidative lesions are the main sources of mtDNA point
mutations, indicating that mtDNA polymerase gamma (POLG) might be responsible for
the majority of mtDNA mutagenic events. Here, we summarize the recent knowledge
in prevention and defence of mtDNA oxidative lesions and discuss the plausible
mechanisms of mtDNA point mutation generation and fixation.
PMID- 28698308
TI - The role of attenuated redox and heat shock protein responses in the age-related
decline in skeletal muscle mass and function.
AB - The loss of muscle mass and weakness that accompanies ageing is a major
contributor to physical frailty and loss of independence in older people. A
failure of muscle to adapt to physiological stresses such as exercise is seen
with ageing and disruption of redox regulated processes and stress responses are
recognized to play important roles in theses deficits. The role of redox
regulation in control of specific stress responses, including the generation of
heat shock proteins (HSPs) by muscle appears to be particularly important and
affected by ageing. Transgenic and knockout studies in experimental models in
which redox and HSP responses were modified have demonstrated the importance of
these processes in maintenance of muscle mass and function during ageing. New
data also indicate the potential of these processes to interact with and
influence ageing in other tissues. In particular the roles of redox signalling
and HSPs in regulation of inflammatory pathways appears important in their impact
on organismal ageing. This review will briefly indicate the importance of this
area and demonstrate how an understanding of the manner in which redox and stress
responses interact and how they may be controlled offers considerable promise as
an approach to ameliorate the major functional consequences of ageing of skeletal
muscle (and potentially other tissues) in man.
PMID- 28698309
TI - Differential control of ageing and lifespan by isoforms and splice variants
across the mTOR network.
AB - Ageing can be defined as the gradual deterioration of physiological functions,
increasing the incidence of age-related disorders and the probability of death.
Therefore, the term ageing not only reflects the lifespan of an organism but also
refers to progressive functional impairment and disease. The nutrient-sensing
kinase mTOR (mammalian target of rapamycin) is a major determinant of ageing.
mTOR promotes cell growth and controls central metabolic pathways including
protein biosynthesis, autophagy and glucose and lipid homoeostasis. The concept
that mTOR has a crucial role in ageing is supported by numerous reports on the
lifespan-prolonging effects of the mTOR inhibitor rapamycin in invertebrate and
vertebrate model organisms. Dietary restriction increases lifespan and delays
ageing phenotypes as well and mTOR has been assigned a major role in this
process. This may suggest a causal relationship between the lifespan of an
organism and its metabolic phenotype. More than 25 years after mTOR's discovery,
a wealth of metabolic and ageing-related effects have been reported. In this
review, we cover the current view on the contribution of the different elements
of the mTOR signalling network to lifespan and age-related metabolic impairment.
We specifically focus on distinct roles of isoforms and splice variants across
the mTOR network. The comprehensive analysis of mouse knockout studies targeting
these variants does not support a tight correlation between lifespan prolongation
and improved metabolic phenotypes and questions the strict causal relationship
between them.
PMID- 28698310
TI - Systems modelling ageing: from single senescent cells to simple multi-cellular
models.
AB - Systems modelling has been successfully used to investigate several key molecular
mechanisms of ageing. Modelling frameworks to allow integration of models and
methods to enhance confidence in models are now well established. In this
article, we discuss these issues and work through the process of building an
integrated model for cellular senescence as a single cell and in a simple tissue
context.
PMID- 28698312
TI - Approaches for extending human healthspan: from antioxidants to healthspan
pharmacology.
AB - Dramatic increases in human lifespan and declining population growth are
monumental achievements but these same achievements have also led to many
societies today ageing at a faster rate than ever before. Extending healthy
lifespan (healthspan) is a key translational challenge in this context. Disease
centric approaches to manage population ageing risk are adding years to life
without adding health to these years. The growing consensus that ageing is driven
by a limited number of interconnected processes suggests an alternative approach.
Instead of viewing each age-dependent disease as the result of an independent
chain of events, this approach recognizes that most age-dependent diseases depend
on and are driven by a limited set of ageing processes. While the relative
importance of each of these processes and the best intervention strategies
targeting them are subjects of debate, there is increasing interest in providing
preventative intervention options to healthy individuals even before overt age
dependent diseases manifest. Elevated oxidative damage is involved in the
pathophysiology of most age-dependent diseases and markers of oxidative damage
often increase with age in many organisms. However, correlation is not causation
and, sadly, many intervention trials of supposed antioxidants have failed to
extend healthspan and to prevent diseases. This does not, however, mean that
reactive species (RS) and redox signalling are unimportant. Ultimately, the most
effective antioxidants may not turn out to be the best geroprotective drugs, but
effective geroprotective interventions might well turn out to also have
excellent, if probably indirect, antioxidant efficacy.
PMID- 28698311
TI - Proteomics and metabolomics in ageing research: from biomarkers to systems
biology.
AB - Age is the single greatest risk factor for a wide range of diseases, and as the
mean age of human populations grows steadily older, the impact of this risk
factor grows as well. Laboratory studies on the basic biology of ageing have shed
light on numerous genetic pathways that have strong effects on lifespan. However,
we still do not know the degree to which the pathways that affect ageing in the
lab also influence variation in rates of ageing and age-related disease in human
populations. Similarly, despite considerable effort, we have yet to identify
reliable and reproducible 'biomarkers', which are predictors of one's biological
as opposed to chronological age. One challenge lies in the enormous mechanistic
distance between genotype and downstream ageing phenotypes. Here, we consider the
power of studying 'endophenotypes' in the context of ageing. Endophenotypes are
the various molecular domains that exist at intermediate levels of organization
between the genotype and phenotype. We focus our attention specifically on
proteins and metabolites. Proteomic and metabolomic profiling has the potential
to help identify the underlying causal mechanisms that link genotype to
phenotype. We present a brief review of proteomics and metabolomics in ageing
research with a focus on the potential of a systems biology and network-centric
perspective in geroscience. While network analyses to study ageing utilizing
proteomics and metabolomics are in their infancy, they may be the powerful model
needed to discover underlying biological processes that influence natural
variation in ageing, age-related disease, and longevity.
PMID- 28698313
TI - HIV and HIV-Tat inhibit LPS-induced IL-27 production in human macrophages by
distinct intracellular signaling pathways.
AB - Monocyte-derived Mphis (MDMs) from HIV-infected patients and MDM infected in
vitro with HIV exhibit a reduced ability to secrete various cytokines, including
IL-12. Recently, IL-27, an IL-12 family cytokine, was shown to inhibit HIV
replication in Mphi. Whether HIV infection or HIV accessory protein(s) impact IL
27 production in Mphis remains unknown. Herein, we show that in vitro HIV
infection, as well as intracellular HIV-Tat (Tat) and Tat peptides, inhibit LPS
induced IL-27 production in human MDMs, suggesting impairment of the TLR4
signaling pathway. To understand the signaling pathways governing HIV or Tat
mediated inhibition of LPS-induced IL-27 production, we first demonstrated that
p38 MAPK, PI3K, Src-homology region 2 domain-containing tyrosine phosphatase 1
(SHP-1), and Src kinases regulate LPS-induced IL-27 production in MDMs. Tat
caused down-regulation of TNFR-associated factor (TRAF)-6 and inhibitor of
apoptosis 1 (cIAP-1) and subsequently decreased phosphorylation of downstream
PI3K and p38 MAPKs, which were implicated in LPS-induced IL-27 production.
Whereas SHP-1 and Src kinases regulated LPS-induced IL-27 production, Tat did not
inhibit these kinases, suggesting that they were not involved in Tat-mediated
inhibition of LPS-induced IL-27 production. In contrast to Tat, in vitro HIV
infection of MDM inhibited LPS-induced IL-27 production via inhibition of p38
MAPK activation. Overall, HIV and Tat inhibit LPS-induced IL-27 production in
human macrophages via distinct mechanisms: Tat through the inhibition of cIAP-1
TRAF-6 and subsequent inhibition of PI3K and p38 MAPKs, whereas HIV through the
inhibition of p38 MAPK activation.
PMID- 28698314
TI - Association of perceived tinnitus with duration of hormone replacement therapy in
Korean postmenopausal women: a cross-sectional study.
AB - OBJECTIVE: The purpose of this study was to determine the relationship between
hormone replacement therapy (HRT) and tinnitus in South Korea using data from the
Korea National Health and Nutrition Examination Surveys (KNHANES) (2010-2012).
STUDY DESIGN: Cross-sectional analysis of a nationwide health survey. METHODS:
KNHANES is a nationally representative cross-sectional survey of South Korea
population. Only postmenopausal women aged 19-65 years were included in the study
(n=2736). Auditory function was evaluated using pure-tone audiometric testing
according to established KNHANES protocols. Subjects were questioned about their
experience with tinnitus. Exogenous hormone-related factors included the starting
age and duration of HRT. RESULTS: The overall prevalence of tinnitus was 22.2%
among postmenopausal women. (1) Tinnitus severity was significantly higher in
women using HRT (p=0.0024) and (2) significantly lower in women who breast fed
their children (p=0.0386). (3) According to logistic regression models, the
longer duration of HRT was significantly associated with increasing tinnitus
(OR=1.323, 95% CI 1.007 to 1.737, p=0.0441). CONCLUSION: A longer duration of HRT
was associated with developing tinnitus in Korean postmenopausal women. Further
experimental and epidemiological researches are needed to elucidate the causal
relationship between HRT and tinnitus.
PMID- 28698315
TI - Translation, adaptation and measurement properties of an electronic version of
the Danish Western Ontario Shoulder Instability Index (WOSI).
AB - OBJECTIVES: To translate and adapt the Western Ontario Shoulder Instability
(WOSI) questionnaire into Danish and, to evaluate measurement properties of an
electronic Danish WOSI version. METHODS: The Swedish WOSI version was used for
translation and adaptation into Danish followed by examination of test-retest
reproducibility (14-day interval) besides concurrent and construct validity.
Concurrent validity was examined by comparing WOSI in paper version with an
electronic version, whereas construct validity was examined by comparing WOSI
with Numeric Pain Rating Scale (NPRS) and the Oxford Shoulder Score (OSS).
Reproducibility was evaluated with Intraclass correlations (ICC), Standard Error
of Measurement (SEM), minimal detectable change (MDC) and limits of agreement
(LOA). Validity was evaluated with Pearson's (r) and Concordance Correlation
Coefficients (CCC). RESULTS: 41 subjects (median age 34, range 18-57) were
included in the analysis of reproducibility. An ICC of 0.97 (95% CI 0.95 to 0.99)
for the total WOSI score was found. SEM was 100.1, resulting in an MDC of 277.5
and LOAs within the range of -246.4 and 308.6. 25 subjects (median age 34, range
18-72) were included in the analysis of concurrent validity obtaining a CCC of
0.96 (95% CI 0.91 to 0.98). Construct validity was investigated in 62 subjects
(median age 31, range 18-72) obtaining correlations of 0.83 (95% CI 0.68 to 0.97)
(NPRS) and 0.79 (95% CI 0.62 to 0.94) (OSS). CONCLUSIONS: An electronic Danish
version of WOSI presented excellent test-retest reproducibility and acceptable
measurement errors. Also, concurrent validity between paper and electronic
version was highly satisfactory as was the construct validity. Surprisingly,
though, the NPRS correlated more with WOSI than OSS.
PMID- 28698316
TI - Description of the rates, trends and surgical burden associated with revision for
prosthetic joint infection following primary and revision knee replacements in
England and Wales: an analysis of the National Joint Registry for England, Wales,
Northern Ireland and the Isle of Man.
AB - OBJECTIVES: To describe the prevalence rates of revision surgery for the
treatment of prosthetic joint infection (PJI) for patients undergoing knee
replacement, their time trends, the cumulative incidence function of revision for
PJI and estimate the burden of PJI at health service level. DESIGN: We analysed
revision knee replacements performed due to a diagnosis of PJI and the linked
index procedures recorded in the National Joint Registry from 2003 to 2014 for
England and Wales. The cohort analysed consisted of 679 010 index primary knee
replacements, 33 920 index revision knee replacements and 8247 revision total
knee replacements performed due to a diagnosis of PJI. The prevalence rates,
their time trends investigated by time from index surgery to revision for PJI,
cumulative incidence functions and the burden of PJI (total procedures) were
calculated. Overall linear trends were investigated with log-linear regression.
RESULTS: The incidence of revision total knee replacement due to PJI at 2 years
was 3.2/1000 following primary and 14.4/1000 following revision knee replacement,
respectively. The prevalence of revision due to PJI in the 3 months following
primary knee replacement has risen by 2.5-fold (95% CI 1.2 to 5.3) from 2005 to
2013 and 7.5-fold (95% CI 1.0 to 56.1) following revision knee replacement. Over
1000 procedures per year are performed as a consequence of knee PJI, an increase
of 2.8 from 2005 to 2013. Overall, 75% of revisions were two-stage with an
increase in use of single-stage from 7.9% in 2005 to 18.8% in 2014. CONCLUSIONS:
Although the risk of revision due to PJI following knee replacement is low, it is
rising, and coupled with the established and further predicted increased
incidence of both primary and revision knee replacements, this represents an
increasing and substantial treatment burden for orthopaedic service delivery in
England and Wales. This has implications for future service design and the
funding of individual and specialist centres.
PMID- 28698317
TI - Retrospective economic analysis of the transfer of services from hospitals to the
community: an application to an enhanced eye care service.
AB - OBJECTIVE: This research aims to evaluate the wider health system effects of the
introduction of an intermediate-tier service for eye care. SETTING: This research
employs the Minor Eye Conditions Scheme (MECS), an intermediate-tier eye care
service introduced in two London boroughs, Lewisham and Lambeth, in April 2013.
DESIGN: Retrospective difference-in-differences analysis comparing changes over
time in service use and costs between April 2011 and October 2014 in two
commissioning areas that introduced an intermediate-tier service programme with
changes in a neighbouring area that did not introduce the programme. DATA
SOURCES: MECS audit data; unit costs for MECS visits; volumes of first and follow
up outpatient attendances to hospital ophthalmology; the national schedule of
reference costs. MAIN OUTCOME MEASURES: Volumes and costs of patients treated.
RESULTS: In one intervention area (Lewisham), general practitioner (GP) referrals
to hospital ophthalmology decreased differentially by 75.2% (95% CI -0.918% to
0.587%) for first attendances, and by 40.3% for follow-ups (95% CI -0.489% to
0.316%). GP referrals to hospital ophthalmology decreased differentially by 30.2%
(95% CI -0.468% to -0.137%) for first attendances in the other intervention area
(Lambeth). Costs increased by 3.1% in the comparison area between 2011/2012 and
2013/2014. Over the same period, costs increased by less (2.5%) in one
intervention area and fell by 13.8% in the other intervention area. CONCLUSIONS:
Intermediate-tier services based in the community could potentially reduce
volumes of patients referred to hospitals by GPs and provide replacement services
at lower unit costs.
PMID- 28698318
TI - Words do matter: a systematic review on how different terminology for the same
condition influences management preferences.
AB - OBJECTIVES: Changing terminology for low-risk, screen-detected conditions has now
been recommended by several expert groups in order to prevent overdiagnosis and
reduce the associated harms of overtreatment. However, the effect of terminology
on patients' preferences for management is not well understood. This review aims
to synthesise existing studies on terminology and its impact on management
decision making. DESIGN: Systematic review. METHODS: Studies were included that
compared two or more terminologies to describe the same condition and measured
the effect on treatment or management preferences and/or choices. Studies were
identified via database searches from inception to April 2017, and from reference
lists. Two authors evaluated the eligibility of studies with verification from
the study team, extracted and crosschecked data, and assessed the risk of bias of
included studies. RESULTS: Of the 1399 titles identified, seven studies, all of
which included hypothetical scenarios, met the inclusion criteria. Six studies
were quantitative and one was qualitative. Six of the studies were of high
quality. Studies covered a diverse range of conditions: ductal carcinoma in situ
(3), gastro-oesophageal reflux disease (1), conjunctivitis (1), polycystic ovary
syndrome (1) and a bony fracture (1). The terminologies compared in each study
varied based on the condition assessed. Based on a narrative synthesis of the
data, when a more medicalised or precise term was used to describe the condition,
it generally resulted in a shift in preference towards more invasive managements,
and/or higher ratings of anxiety and perceived severity of the condition.
CONCLUSIONS: Different terminology given for the same condition influenced
management preferences and psychological outcomes in a consistent pattern in
these studies. Changing the terminology may be one strategy to reduce patient
preferences for aggressive management responses to low-risk conditions. TRIAL
REGISTRATION NUMBER: PROSPERO: CRD42016035643.
PMID- 28698319
TI - The Supporting Patient Activation in Transition to Home (sPATH) intervention: a
study protocol of a randomised controlled trial using motivational interviewing
to decrease re-hospitalisation for patients with COPD or heart failure.
AB - INTRODUCTION: Deficient hospital discharging and patients struggling to handle
postdischarge self-management have been identified as potential causes of re
hospitalisation rates. Despite an increased interest in interventions aiming to
reduce re-hospitalisation rates, there is yet no best evidence on how to support
patients in being active participants in their self-management postdischarge. The
aim of this paper is to describe the study protocol for an upcoming randomised
controlled trial (RCT) of the Supporting Patient in Activation to Home (sPATH)
intervention. METHODS/ANALYSIS: The described study is a randomised, controlled,
analysis-blinded, two-site trial, with primary outcome re-hospitalisation within
90 days. In total, 290 participants aged 18 years or older with chronic
obstructive pulmonary disease or congestive heart failure who are admitted to
hospital and who are living in an own home will be eligible for inclusion into an
intervention (n=145) or control group (n=145). Patients who need an interpreter
to communicate in Swedish, or who have a diagnosis of dementia or cognitive
impairment, will be excluded from inclusion. The sPATH intervention, developed
with a theoretical base in the self-determination theory, consists of five
postdischarge motivational interviewing sessions (face to face or by phone). The
intervention covers the self-management areas medication management, follow
up/care plan, symptoms/signs of worsening condition and relations/contacts with
healthcare providers. This RCT will add to the literature on evidence to support
patient activation in postdischarge self-management. ETHICS AND DISSEMINATION:
The study is approved by the Regional Research Ethics Committee (No. 2014/1498
31/2) in Stockholm, Sweden. The results of the study will be published in peer
reviewed journals and presented at international and national scientific
conferences. TRIAL REGISTRATION NUMBER: NCT02823795; Pre-results.
PMID- 28698320
TI - A Self-Management Programme of Activity Coping and Education - SPACE for COPD(C)
in primary care: The protocol for a pragmatic trial.
AB - INTRODUCTION: National guidance for chronic obstructive pulmonary disease (COPD)
suggests that self-management support be provided for patients. Our institution
has developed a standardised, manual-based, supported self-management programme:
Self-Management Programme of Activity Coping and Education (SPACE for COPD(C)).
SPACE was previously piloted on a 1-2-1 basis, delivered by researchers, to
individuals with COPD. Discussions with stakeholders highlighted considerable
interest in delivering the SPACE for COPD(C) intervention as a group-based self
management programme facilitated by healthcare professionals (HCPs) in primary
care settings. The study aims are to explore the feasibility, acceptability and
efficacy for the intervention to be delivered and supported by HCPs and to
examine whether group-based delivery of SPACE for COPD(C), with sustained
support, improves patient outcomes following the SPACE for COPD(C) intervention.
METHODS AND ANALYSIS: A prospective, multi-site, single-blinded randomised
controlled trial (RCT) will be conducted, with follow-up at 6 and 9 months.
Participants will be randomly assigned to either the control group (usual care)
or intervention group (a six-session, group-based SPACE for COPD(C)self
management programme delivered over 5 months). The primary outcome is change in
COPD assessment test at 6 months.A discussion session will be conducted with HCPs
who deliver the intervention to discuss and gain insight into any potential
facilitators/barriers to implementing the intervention in practice. Furthermore,
we will conduct semi-structured focus groups with intervention participants to
understand feasibility and acceptability. All qualitative data will be analysed
thematically. ETHICS AND DISSEMINATION: The project has received a favourable
opinion from South Hampshire B Research Ethics Committee, REC reference:
14/SC/1169 and full R&D approval from the University Hospitals of Leicester NHS
Trust: 152408.Study results will be disseminated through appropriate peer
reviewed journals, national and international respiratory/physiotherapy
conferences, via the Collaboration and Leadership in Applied Health Research and
Care and through social media. TRIAL REGISTRATION: ISRCTN17942821; pre-results.
PMID- 28698321
TI - Factors associated with non-persistence to oral and inhaled antiviral therapies
for seasonal influenza: a secondary analysis of a double-blind, multicentre,
randomised clinical trial.
AB - OBJECTIVES: We aimed to evaluate and compare non-adherence to oral and inhaled
antiviral therapies prescribed of a randomised clinical trial in outpatients with
influenza A infection. DESIGN: A parallel, three-arm, double-blinded trial
randomly allocated antiviral therapies twice daily for 5 days: (1) oral
oseltamivir plus inhaled zanamivir (arm OZ); (2) oseltamivir plus inhaled placebo
(arm Opz); or (3) oral placebo plus inhaled zanamivir (arm poZ). Analysis of non
adherence was a secondary objective of the trial. SETTINGS: Outpatients were
enrolled by 145 general practitioners throughout France during the 2008-2009
seasonal influenza epidemics. PARTICIPANTS: A total of 541 adults presenting with
influenza-like illness for less than 36 hours. PRIMARY OUTCOMES: Non-persistence,
the time between inclusion and the last dose treated as a failure time, was used
as the primary endpoint. RESULTS: The proportions of patients who persisted on
treatment until the end of prescription were estimated at 85.73% (+/-3.28%) for
the oral route and 82.73% (+/-3.44%) for the inhaled route. Based on
multivariable models, non-persistence was associated with a PCR confirmation of
influenza for both the oral (HR=0.54, p=0.010) and inhaled (HR=0.59, p=0.018)
drugs and antibiotic coprescriptions (HR=2.07, p=0.007; and HR=1.88, p=0.017,
respectively) and active combination treatment (HR=1.71, p=0.035; and HR=1.58,
p=0.035, respectively). The hazard of non-persistence of the inhaled therapy was
increased compared with that of the oral therapy (HR=1.23, p=0.043). CONCLUSION:
In addition to the clinical and virological profiles of influenza infection, non
persistence may have been influenced by an active combination and the route of
administration. RCT REGISTRATION NUMBER: NCT00799760. This is a post-result
analysis.
PMID- 28698322
TI - Perceived impacts of the national essential medicines system: a cross-sectional
survey of health workers in urban community health services in China.
AB - OBJECTIVES: This study aimed to investigate the perceptions of primary care
workers about the impacts of the national essential medicines policy (NEMP).
SETTING: A cross-sectional questionnaire survey was undertaken in 42 urban
community health centres randomly selected from four provinces in China.
PARTICIPANTS: 791 primary care workers rated the impacts of the NEMP on a 5-point
Likert scale. OUTCOME MEASURES: An average score for the impacts of the NEMP on
four aspects (the practice of health workers, interactions of patients with
health workers, operations of health centres and provision of medicines) was
calculated, each ranging from 0 to 100. A higher score indicates a more positive
rating. Linear regression models were established to determine the
sociodemographic characteristics (region, age, gender, profession, training,
income) that were associated with the ratings. RESULTS: The respondents gave an
average rating score of 65.61+/-11.76, 63.17+/-13.62, 66.35+/-13.02 and 67.26+/
11.60 for the impacts of the NEMP on health workers, patients, health centres and
provision of medicines, respectively. Respondents from the central region rated
the NEMP higher than those from the eastern and western regions. The pharmacists
(beta=5.457~7.558, p<0.001) and nurses (beta=2.612~3.107, p<0.05) gave a more
positive rating on the NEMP than their physician counterparts. A higher income
was found to be associated with a decrease in the NEMP ratings. Repetitive
training was a predictor of higher ratings. CONCLUSIONS: The NEMP has significant
impacts (as perceived by the health workers) on health services delivery in
primary care settings. However, the impacts of the NEMP vary by region,
professional practice and the income level of health workers. It is important to
maintain support from physicians through income subsidies (to compensate for
potential loss) and training.
PMID- 28698323
TI - Performance of highly sensitive cardiac troponin T assay to detect ischaemia at
PET-CT in low-risk patients with acute coronary syndrome: a prospective
observational study.
AB - BACKGROUND: Highly sensitive troponin T (hs-TnT) assay has improved clinical
decision-making for patients admitted with chest pain. However, this assay's
performance in detecting myocardial ischaemia in a lowrisk population has been
poorly documented. PURPOSE: To assess hs-TnT assay's performance to detect
myocardial ischaemia at positron emission tomography/CT (PET-CT) in low-risk
patients admitted with chest pain. METHODS: Patients admitted for chest pain with
a nonconclusive ECG and negative standard cardiac troponin T results at admission
and after 6 hours were prospectively enrolled. Their hs-TnT samples were at T0,
T2 and T6. Physicians were blinded to hs-TnT results. All patients underwent a
PET-CT at rest and during adenosine-induced stress. All patients with a positive
PET-CT result underwent a coronary angiography. RESULTS: Forty-eight patients
were included. Six had ischaemia at PET-CT. All of them had >=1 significant
stenosis at coronary angiography. Areas under the curve (95% CI) for predicting
significant ischaemia at PET-CT using hs-TnT were 0.764 (0.515 to 1.000) at T0,
0.812(0.616 to 1.000) at T2 and 0.813(0.638 to 0.989) at T6. The receiver
operating characteristicbased optimal cut-off value for hs-TnT at T0, T2 and T6
needed to exclude significant ischaemia at PET-CT was <4 ng/L. Using this value,
sensitivity, specificity, positive and negative predictive values of hs-TnT to
predict significant ischaemia were 83%/38%/16%/94% at T0, 100%/40%/19%/100% at T2
and 100%/43%/20%/100% at T6, respectively. CONCLUSIONS: Our findings suggest that
in low-risk patients, using the hs-TnT assay with a cut-off value of 4 ng/L
demonstrates excellent negative predictive value to exclude myocardial ischaemia
detection at PET-CT, at the expense of weak specificity and positive predictive
value. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Identifier: NCT01374607.
PMID- 28698324
TI - The Women and Their Children's Health (WaTCH) study: methods and design of a
prospective cohort study in Louisiana to examine the health effects from the BP
oil spill.
AB - PURPOSE: The Deepwater Horizon Oil Spill is the largest marine oil spill in US
history. Few studies have evaluated the potential health effects of this spill on
the Gulf Coast community. The Women and Their Children's Health (WaTCH) study is
a prospective cohort designed to investigate the midterm to long-term physical,
mental and behavioural health effects of exposure to the oil spill. PARTICIPANTS:
Women were recruited by telephone from pre-existing lists of individuals and
households using an address-based sampling frame between 2012 and 2014. Baseline
interviews obtained information on oil spill exposure, demographics, physical and
mental health, and health behaviours. Women were also asked to provide a
household roster, from which a child between 10 and 17 years was randomly
selected and recruited into a child substudy. Telephone respondents were invited
to participate in a home visit in which blood samples, anthropometrics and
neighbourhood characteristics were measured. A follow-up interview was completed
between 2014 and 2016. FINDINGS TO DATE: 2852 women completed the baseline
interview, 1231 of whom participated in the home visit, and 628 children
participated in the child's health substudy. The follow-up interview successfully
reinterviewed 2030 women and 454 children. FUTURE PLANS: WaTCH continues to
conduct follow-up surveys, with a third wave of interviews planned in 2017. Also,
we are looking to enhance the collection of spatially related environmental data
to facilitate assessment of health risks in the study population. In addition,
opportunities to participate in behavioural interventions for subsets of the
cohort have been initiated. There are ongoing studies that examine the
relationship between genetic and immunological markers with mental health.
PMID- 28698325
TI - The Scottish school leavers cohort: linkage of education data to routinely
collected records for mortality, hospital discharge and offspring birth
characteristics.
AB - PURPOSE: The Scottish school leavers cohort provides population-wide prospective
follow-up of local authority secondary school leavers in Scotland through linkage
of comprehensive education data with hospital and mortality records. It considers
educational attainment as a proxy for socioeconomic position in young adulthood
and enables the study of associations and causal relationships between
educational attainment and health outcomes in young adulthood. PARTICIPANTS:
Education data for 284 621 individuals who left a local authority secondary
school during 2006/2007-2010/2011 were linked with birth, death and hospital
records, including general/acute and mental health inpatient and day case
records. Individuals were followed up from date of school leaving until September
2012. Age range during follow-up was 15 years to 24 years. FINDINGS TO DATE:
Education data included all formal school qualifications attained by date of
school leaving; sociodemographic information; indicators of student needs,
educational or non-educational support received and special school unit
attendance; attendance, absence and exclusions over time and school leaver
destination. Area-based measures of school and home deprivation were provided.
Health data included dates of admission/discharge from hospital;
principal/secondary diagnoses; maternal-related, birth-related and baby-related
variables and, where relevant, date and cause of death. This paper presents crude
rates for all-cause and cause-specific deaths and general/acute and psychiatric
hospital admissions as well as birth outcomes for children of female cohort
members. FUTURE PLANS: This study is the first in Scotland to link education and
health data for the population of local authority secondary school leavers and
provides access to a large, representative cohort with the ability to study rare
health outcomes. There is the potential to study health outcomes over the life
course through linkage with future hospital and death records for cohort members.
The cohort may also be expanded by adding data from future school leavers. There
is scope for linkage to the Prescribing Information System and the Scottish
Primary Care Information Resource.
PMID- 28698326
TI - MiYoga: a randomised controlled trial of a mindfulness movement programme based
on hatha yoga principles for children with cerebral palsy: a study protocol.
AB - INTRODUCTION: Cerebral palsy (CP) is the most common childhood physical
disability, with life-long impacts for 1.77 in 1000 children. Although CP is
primarily a physical disability, children with CP have an increased risk of
experiencing cognitive difficulties, particularly attention and executive
function deficits. Impairment in cognitive abilities can lead to subsequent
impairment in independent functioning, education, employment and interpersonal
relationships. This paper reports the protocol of a randomised controlled trial
of a novel family-centred lifestyle intervention based on mindfulness and hatha
yoga principles (MiYoga). MiYoga aims to enhance child and parent outcomes for
children with CP. METHODS AND ANALYSIS: The aim is to recruit 36 child-parent
dyads (children aged 6-16 years; bilateral or unilateral CP; Gross Motor Function
Classification System I-III), who will be randomly assigned to two groups: MiYoga
andwaitlistt control. The MiYoga programme will be facilitated in a group format
for 8 weeks. Assessments will be administered at baseline, prior to MiYoga,
following completion of MiYoga, and at 6-month follow-up (retention). The primary
outcome will be the child's sustained attentional ability as measured by the
Conner's Continuous Performance Test II. Other outcomes of interest for children
with CP consists of attentional control, physical functioning, behavioural and
well-being. For parents, the outcomes of interest are mindfulness, psychological
flexibility and well-being. Data will be analysed using general linear models,
specifically analysis of covariance and analysis of variance. ETHICS AND
DISSEMINATION: Full ethical approval for this study has been obtained by the
Children's Health Queensland Hospital and Health Service Research Ethics
Committee (HREC/12/QRCH/120) and The University of Queensland (2012000993). If
MiYoga is proven effective, its dissemination would assist children with CP and
complement their ongoing therapy by improving the ability of the child to pay
attention at school and in therapy, and alleviating environmentalstressorss for
both the child and his/her parents. TRIAL REGISTRATION NUMBER:
ACTRN12613000729729; Pre
results.http://www.ANZCTR.org.au/ACTRN12613000729729.aspx DATE OF TRIAL
REGISTRATION: Prospectively registered on 2 July 2013-present (ongoing). FINDINGS
TO DATE: Recruitment is complete. Data are still being collected at present. We
aim to complete data collection by February 2017.
PMID- 28698327
TI - Bubble continuous positive airway pressure in the treatment of severe paediatric
pneumonia in Malawi: a cost-effectiveness analysis.
AB - OBJECTIVES: Pneumonia is the largest infectious cause of death in children under
5 years globally, and limited resource settings bear an overwhelming proportion
of this disease burden. Bubble continuous positive airway pressure (bCPAP), an
accepted supportive therapy, is often thought of as cost-prohibitive in these
settings. We hypothesise that bCPAP is a cost-effective intervention in a limited
resource setting and this study aims to determine the cost-effectiveness of
bCPAP, using Malawi as an example. DESIGN: Cost-effectiveness analysis. SETTING:
District and central hospitals in Malawi. PARTICIPANTS: Children aged 1 month-5
years with severe pneumonia, as defined by WHO criteria. INTERVENTIONS: Using a
decision tree analysis, we compared standard of care (including low-flow oxygen
and antibiotics) to standard of care plus bCPAP. PRIMARY AND SECONDARY OUTCOME
MEASURES: For each treatment arm, we determined the costs, clinical outcomes and
averted disability-adjusted life years (DALYs). We assigned input values from a
review of the literature, including applicable clinical trials, and calculated an
incremental cost-effectiveness ratio (ICER). RESULTS: In the base case analysis,
the cost of bCPAP per patient was $15 per day and $41 per hospitalisation, with
an incremental net cost of $64 per pneumonia episode. bCPAP averts 5.0 DALYs per
child treated, with an ICER of $12.88 per DALY averted compared with standard of
care. In one-way sensitivity analyses, the most influential uncertainties were
case fatality rates (ICER range $9-32 per DALY averted). In a multi-way
sensitivity analysis, the median ICER was $12.97 per DALY averted (90% CI, $12.77
to $12.99). CONCLUSION: bCPAP is a cost-effective intervention for severe
paediatric pneumonia in Malawi. These results may be used to inform policy
decisions, including support for widespread use of bCPAP in similar settings.
PMID- 28698328
TI - Evaluation of the organisation and effectiveness of internal audits to govern
patient safety in hospitals: a mixed-methods study.
AB - OBJECTIVES: Hospital boards are legally responsible for safe healthcare. They
need tools to assist them in their task of governing patient safety. Almost every
Dutch hospital performs internal audits, but the effectiveness of these audits
for hospital governance has never been evaluated. The aim of this study is to
evaluate the organisation of internal audits and their effectiveness for
hospitals boards to govern patient safety. DESIGN AND SETTING: A mixed-methods
study consisting of a questionnaire regarding the organisation of internal audits
among all Dutch hospitals (n=89) and interviews with stakeholders regarding the
audit process and experienced effectiveness of audits within six hospitals.
RESULTS: Response rate of the questionnaire was 76% and 43 interviews were held.
In every responding hospital, the internal audits followed the plan-do-check-act
cycle. Every hospital used interviews, document analysis and site visits as input
for the internal audit. Boards stated that effective aspects of internal audits
were their multidisciplinary scope, their structured and in-depth approach, the
usability to monitor improvement activities and to change hospital policy and the
fact that results were used in meetings with staff and boards of supervisors. The
qualitative methods (interviews and site visits) used in internal audits enable
the identification of soft signals such as unsafe culture or communication and
collaboration problems. Reported disadvantages were the low frequency of internal
audits and the absence of soft signals in the actual audit reports. CONCLUSION:
This study shows that internal audits are regarded as effective for patient
safety governance, as they help boards to identify patient safety problems,
proactively steer patient safety and inform boards of supervisors on the status
of patient safety. The description of the Dutch internal audits makes these
audits replicable to other healthcare organisations in different settings,
enabling hospital boards to complement their systems to govern patient safety.
PMID- 28698329
TI - A cross-sectional study using freedom of information requests to evaluate
variation in local authority commissioning of community pharmacy public health
services in England.
AB - OBJECTIVES: This study aims to provide a national picture of the extent and
nature of public health services commissioned by local authorities (LAs) from
community pharmacies across England in financial year 2014/15. DESIGN: Cross
sectional survey of public health services commissioned in community pharmacies
by LAs, gathered via freedom of information requests and documentary analysis.
SETTING AND PARTICIPANTS: All 152 LAs in England. RESULTS: A total of 833
commissioned services were reported across England (range 3-10 per LA). Four
services were commissioned by over 90% of LAs: emergency hormonal contraception
(EHC), smoking cessation support, supervised consumption of methadone or other
opiates and needle and syringe programmes (NSPs). The proportion of pharmacies
commissioned to deliver these services varied considerably between LAs from <10%
to 100%. This variation was not related to differences in relevant proxy measures
of need. NHS Health Checks and alcohol screening and brief advice were
commissioned by fewer LAs (32% and 15%, respectively), again with no relationship
to relevant measures of need. A range of other services were commissioned less
frequently, by fewer than 10% of LAs.Supervised consumption and NSPs were the
most frequently used services, with over 4.4 million individual supervisions and
over 1.4 million needle packs supplied. Pharmacies provided over 200 000
consultations for supply of EHC, over 30 000 supplies of free condoms and almost
16 000 chlamydia screening kits. More than 55 000 people registered to stop
smoking in a community pharmacy, almost 30 000 were screened for alcohol use and
over 26 000 NHS Health Checks were delivered. CONCLUSIONS: There is significant
variation in commissioning and delivery of public health services in community
pharmacies across England, which correlate poorly with potential benefit to local
populations. Research to ascertain reasons for this variation is needed to ensure
that future commissioning and delivery of these services matches local need.
PMID- 28698330
TI - Clinical characteristics of importance to outcome in patients with axial
spondyloarthritis: protocol for a prospective descriptive and exploratory cohort
study.
AB - INTRODUCTION: Spondyloarthritis (SpA) is a heterogeneous spectrum of rheumatic
diseases with either predominantly axial inflammatory symptoms of the spine and
sacroiliac joints or predominantly peripheral arthritis. The two main entities of
axial SpA (axSpA) are ankylosing spondylitis or non-radiographic axSpA (nr
axSpA). Tumour necrosis factor-alpha inhibitors have revolutionised the treatment
of patients with axSpA who failed to respond to non-steroidal anti-inflammatory
drugs and physical therapy. Chronic pain is common in patients with SpA and may
still persist despite the lack of signs of inflammation. This has led researchers
to hypothesise that central pain sensitisation may play a role in the generation
of chronic pain in SpA. The painDETECT Questionnaire (PDQ) is a screening tool
developed to detect neuropathic pain components. The primary objective is to
explore the prognostic value of the PDQ regarding treatment response in patients
with axSpA 3 months after initiating a biological agent. Secondary aim is to
evaluate the impact of extra-articular manifestations, comorbidities and patient
reported outcomes and elucidate if these factors influence treatment response.
METHOD AND ANALYSIS: We will include 60 participants (>=18 years of age)
diagnosed with axSpA independent of main entity, who initiate or switch treatment
of a biologic. Data will be collected at baseline and at endpoint following
Danish clinical practice (>=3 months) of treatment with biologics. We will
explore whether the PDQ and other phenotypical patient characteristics are
prognostically important for response to biological therapy according to
established response criteria like 50% improvement in the Bath Ankylosing
Spondylitis Disease Activity Index (50%) and Ankylosing Spondylitis Disease
Activity Score. ETHICS AND DISSEMINATION: The study is approved by the Region of
Southern Denmark's Ethics committee (S-20160094) and has been designed in
cooperation with patient representatives. The study is registered at
clinicaltrials.gov (NCT02948608, pre-results). Dissemination will occur through
publication(s) in international peer-reviewed journal(s).
PMID- 28698331
TI - Efficacy of conventional treatment with composite resin and atraumatic
restorative treatment in posterior primary teeth: study protocol for a randomised
controlled trial.
AB - INTRODUCTION: Despite the widespread acceptance of conventional treatment using
composite resin in primary teeth, there is limited evidence that this approach is
the best option in paediatric clinics. Atraumatic restorative treatment (ART)
using high-viscosity glass ionomer cement has gradually become more popular
because it performs well in clinical studies, is easy to handle and is patient
friendly. Therefore, the aim of this randomised clinical trial study is to
compare the restoration longevity of conventional treatment using composite resin
with that of ART in posterior primary teeth. As secondary outcomes, cost-efficacy
and patient self-reported discomfort will also be tested. METHODS AND ANALYSIS:
Children aged 3-6 years presenting with at least one occlusal and/or occlusal
proximal cavity will be randomly assigned to one of two groups according to the
dental treatment: ART (experimental group) or composite resin restoration
(control group). The dental treatment will be performed at a dental care trailer
located in an educational complex in Barueri/SP, Brazil. The unit of
randomisation will be the child. A sample size of 240 teeth with occlusal
cavities and 188 teeth with occlusal-proximal cavities has been calculated. The
primary outcome will be restoration longevity, which will be clinically assessed
after 6, 12, 18 and 24 months by two examiners. The duration of the dental
treatment and the cost of all materials used will be considered when estimating
the cost-efficacy of each treatment. Individual discomfort will be measured after
each dental procedure using the Facial Scale of Wong-Baker. ETHICS AND
DISSEMINATION: This clinical trial was approved by the local ethics committee
from the Faculty of Dentistry of the University of Sao Paulo (registration no.
1.556.018). Participants will be included after their legal guardians have signed
an informed consent form containing detailed information about the research.
TRIAL REGISTRATION NUMBER: www.clinicaltrials.gov, NCT02562456; Pre-results.
PMID- 28698332
TI - Development in the number of clinical trial applications in Western Europe from
2007 to 2015: retrospective study of data from national competent authorities.
AB - OBJECTIVE: To investigate the development in the number of applications for
authorisation of clinical trials of medicines (CTAs) submitted annually to
national competent authorities in 10 Western European member states of the
European Union from 2007 to 2015. DESIGN: Registry study. SETTING: Data from
national competent authorities. PARTICIPANTS: Germany, Italy, Spain, France, the
UK, Belgium, the Netherlands, Austria, Denmark and Sweden. Inclusion criteria
were Western European member states of the European Union, receiving more than
200 CTAs per year. OUTCOME MEASURES: Summarised number of CTAs and distribution
of CTAs by type of sponsor (commercial or non-commercial) and trial phase (I-IV).
Average annual growth rates (AAGRs) based on linear regressions. Data were
evaluated 2007-2011 and 2012-2015 to compare findings with the European
Commission's statement of a 25% decrease in CTAs in the EU from 2007 to 2011.
RESULTS: From 2007 to 2011, the summarised number of CTAs decreased significantly
(AAGR -3.9% (p=0.02)), primarily due to a decrease in commercially sponsored
CTAs. From 2012 to 2015, the change was insignificant (AAGR 2.6% (p=0.27)),
however with a 10% increase from 2014 to 2015 after stagnation from 2012 to 2014.
Overall, the number of CTAs and distribution by type of sponsor varied
considerably between countries. No distinct trends were observed when evaluating
CTAs by type of trial phase. CONCLUSIONS: This study found a significant decrease
in the number of CTAs in Western Europe from 2007 to 2011 (AAGR -3.9%). This
development is possibly attributable to several factors such as the European
Clinical Trials Directive, national and local political decisions, and a
potential global shift in clinical trial activity. From 2014 to 2015, the number
of CTAs increased markedly (10%). However, it is yet too soon to determine if
this constitutes a transient fluctuation or a new trend.
PMID- 28698333
TI - Research protocol for platelets in out-of-hospital cardiac arrest: an
observational, case-controlled, feasibility study to assess coagulation and
platelet function abnormalities with ROTEM following out-of-hospital cardiac
arrest (PoHCAR).
AB - INTRODUCTION: Out-of-hospital cardiac arrest (OHCA) has an annual incidence of
approximately 60 000 in the UK. Less than 10% of those who receive resuscitation
survive to hospital discharge. For OHCA of a presumed cardiac cause, the optimal
antiplatelet therapy is currently unknown. Previous studies indicate that a
procoagulopathic state exists postcardiac arrest which may contribute to the
formation of thrombi and contribute to poor outcomes. However, the administration
of antiplatelet therapies needs to be balanced against the increased risk of
bleeding that these individuals face. METHODS AND ANALYSIS: This observational
feasibility study will recruit 30 individuals who achieve return of spontaneous
circulation post-OHCA, are admitted to a single tertiary centre over a 6-month
period and meet Utstein cohort criteria (witnessed cardiac arrest, VF or
pulseless VT and cardiac cause of arrest likely). Rotational thromboelastometry
and platelet function assessment will be performed on hospital arrival,
postemergency percutaneous coronary intervention (PCI) and 12 hours, 24 hours and
48 hours post-PCI. As a comparator, 30 individuals presenting to our institution
with ST-segment elevation myocardial infarction and undergoing primary PCI will
have the same blood sampling performed. Plasma samples will be retained and batch
tested on completion of the study for levels of protein C, protein S, thrombin
antithrombin complex, thrombin, antithrombin, plasminogen activator inhibitor-1,
plasmin-antiplasmin complex, d-dimer, platelet factor-4, P selectin, E selectin
and prothrombin fragments 1 and 2. 30-day follow-up for complications will be
undertaken. ETHICS AND DISSEMINATION: This study has been approved by the Wales
REC 7Research Ethics Committee. The results will be submitted to peer-reviewed
medical journals and suitable national and international meetings. Results will
be locally disseminated via our patient and public interest group. TRIAL
REGISTRATION NUMBER: Pre-results; ISRCTN34122839.
PMID- 28698334
TI - A randomised controlled trial to evaluate the impact of sexual health clinic
based automated text message reminders on testing of HIV and other sexually
transmitted infections in men who have sex with men in China: protocol for the
T2T Study.
AB - INTRODUCTION: The frequency of screening for HIV and other sexually transmitted
infections (STIs) among men who have sex with men (MSM) is still low in China.
METHODS AND ANALYSIS: A sexual health clinic based randomised controlled trial
will be conducted in Guangzhou, Wuxi and Shenzhen, China, enrolling 600 MSM.
Eligibility will be judged by the pre-programed iPad based questionnaire: (1) age
>=18 years and (2) have had two or more male anal sex partners, or condomless
anal sex with a casual male sex partner, or an STI history, in the past 6 months,
and (3) provides a valid mobile phone number. Eligible men will be randomly
allocated 1:1 to the intervention arm (with monthly text messages reminding them
to test for HIV/STIs) or to the control arm (with no reminders). Men in both arms
will complete a questionnaire onsite at enrolment and after 12 months, and
another questionnaire online at 6 months. Men in both arms will be tested for
HIV, syphilis, anal gonorrhoea/chlamydia and penile gonorrhoea/chlamydia at
enrolment and at 12 months. The primary outcome is the rate and frequency of HIV
testing within the 12 months after enrolment. The secondary outcome is the rate
of unprotected anal intercourse. An assessment of the cost effectiveness of this
intervention is also planned. ETHICS AND DISSEMINATION: The study has been
approved by the ethical review committees of the University of New South Wales,
Australia (HC16803), the Guangdong Provincial Centre for Skin Disease and STI
Control (GDDHLS-20160926) and the Wuxi Centre for Disease Control and Prevention
(WXCDC2016009), China. Study findings will be submitted to academic journals and
disseminated to local health authorities. TRIAL REGISTRATION NUMBER: Chinese
Clinical Trial Registry at: http://www.chictr.org.cn/showprojen.aspx?proj=15752
and WHO International Clinical Trials Registry Platform at:
http://apps.who.int/trialsearch/Trial2.aspx?TrialID=ChiCTR-IOR-16009304.
PMID- 28698335
TI - Risk of a seizure recurrence after a breakthrough seizure and the implications
for driving: further analysis of the standard versus new antiepileptic drugs
(SANAD) randomised controlled trial.
AB - OBJECTIVES: A breakthrough seizure is one occurring after at least 12 months
seizure freedom while on treatment. The Driver and Vehicle Licensing Agency
(DVLA) allows an individual to return to driving once they have been seizure free
for 12 months following a breakthrough seizure. This is based on the assumption
that the risk of a further seizure in the next 12 months has dropped <20%. This
analysis considers whether the prescribed 1 year off driving following a
breakthrough seizure is sufficient for this and stratifies risk according to
clinical characteristics. DESIGN, SETTING, PARTICIPANTS, INTERVENTIONS AND MAIN
OUTCOME MEASURES: The multicentre UK-based Standard versus New Antiepileptic
Drugs (SANAD) study was a randomised controlled trial assessing standard and new
antiepileptic drugs for patients with newly diagnosed epilepsy. For participants
aged at least 16 with a breakthrough seizure, data have been analysed to estimate
the annual seizure recurrence risk following a period of 6, 9 and 12 months
seizure freedom. Regression modelling was used to investigate how antiepileptic
drug treatment and a number of clinical factors influence the risk of seizure
recurrence. RESULTS: At 12 months following a breakthrough seizure, the overall
unadjusted risk of a recurrence over the next 12 months is lower than 20%, risk
17% (95% CI 15% to 19%). However, some patient subgroups have been identified
which have an annual recurrence risk significantly greater than 20% after an
initial 12-month seizure-free period following a breakthrough seizure.
CONCLUSIONS: This reanalysis of SANAD provides estimates of seizure recurrence
risks following a breakthrough seizure that will inform policy and guidance about
regaining an ordinary driving licence. Further guidance is needed as to how such
data should be used. TRIAL REGISTRATION NUMBER: SANAD is registered with the
International Standard Randomised Controlled Trial Number Register
ISRCTN38354748.
PMID- 28698336
TI - The characteristics of national health initiatives promoting earlier cancer
diagnosis among adult populations: a systematic review protocol.
AB - INTRODUCTION: The increasing burden of cancer morbidity and mortality has led to
the development of national health initiatives to promote earlier cancer
diagnosis and improve cancer survival. This protocol describes a systematic
review aiming to identify the evidence about such initiatives among the adult
population. We will describe their components, stakeholders and target
populations, and summarise their outcomes. METHODS AND ANALYSIS: We will search
databases and websites for peer-reviewed publications and grey literature on
national health initiatives in high-income countries as defined by the World
Bank. Quantitative, qualitative and mixed-methods studies will be included and
assessed for their methodological quality. Study selection, quality assessment
and data extraction will be carried out independently by two reviewers. Narrative
synthesis will be used to analyse the findings. ETHICS AND DISSEMINATION: This
systematic review analyses secondary data and ethical approval is not required.
Review findings will be helpful to researchers, policy makers, governments and
other key stakeholders developing similar initiatives and assessing cancer
outcomes. The results will be submitted to a peer-reviewed journal in order to
reach a diverse group of healthcare professionals, researchers and policy makers.
This systematic review protocol is registered at PROSPERO (CRD42016047233).
PMID- 28698337
TI - Protocol for a multicentre randomised feasibility STUdy evaluating the impact of
a prognostic model for Management of BLunt chest wall trauma patients: STUMBL
trial.
AB - INTRODUCTION: A new prognostic model has been developed and externally validated,
the aim of which is to assist in the management of the blunt chest wall trauma
patient in the emergency department (ED). A definitive randomised controlled
trial (impact trial) is required to assess the clinical and cost effectiveness of
the new model before it can be accepted in clinical practice. The purpose of this
trial is to assess the feasibility and acceptability of such a definitive trial
and inform its design. METHODS/ANALYSIS: This feasibility trial is designed to
test the methods of a multicentre, cluster-randomised (stepped- wedge) trial,
with a substantial qualitative component. Four EDs in England and Wales will
collect data for all blunt chest wall trauma patients over a 5-month period; in
the initial period acting as the controls (normal care), and in the second period
acting as the interventions (in which the new model will be used). Baseline
measurements including completion of the SF-12v2 will be obtained on initial
assessment in the ED. Patient outcome data will then be collected for any
subsequent hospitalisations. Data collection will conclude with a 6-week follow
up completion of two surveys (SF-12v2 and Client Services Receipt Inventory).
Analysis of outcomes will focus on feasibility, acceptability and trial processes
and will include recruitment and retention rates, attendance at clinician
training rates and use of model in the ED. Qualitative feedback will be obtained
through clinician interviews and a research nurse focus group. An evaluation of
the feasibility of health economics outcomes data will be completed. ETHICS AND
DISSEMINATION: Wales Research Ethics Committee 6 granted approval for the trial
in September 2016. Patient recruitment will commence in February 2017. Planned
dissemination is through publication in a peer-reviewed Emergency Medicine
Journal, presentation at appropriate conferences and to stakeholders at
professional meetings. TRIAL REGISTRATION NUMBER: ISRCTN95571506; Pre-results.
PMID- 28698338
TI - Optimal cut points of plasma and urine neutrophil gelatinase-associated lipocalin
for the prediction of acute kidney injury among critically ill adults:
retrospective determination and clinical validation of a prospective multicentre
study.
AB - OBJECTIVES: To determine the optimal threshold of blood and urine neutrophil
gelatinase-associated lipocalin (NGAL) to predict moderate to severe acute kidney
injury (AKI) and persistent moderate to severe AKI lasting at least 48
consecutive hours, as defined by an adjudication panel. METHODS: A multicentre
prospective observational study enrolled intensive care unit (ICU) patients and
recorded daily ethylenediaminetetraacetic acid (EDTA) plasma, heparin plasma and
urine NGAL. We used natural log-transformed NGAL in a logistic regression model
to predict stage 2/3 AKI (defined by Kidney Disease International Global
Organization). We performed the same analysis using the NGAL value at the start
of persistent stage 2/3 AKI. RESULTS: Of 245 subjects, 33 (13.5%) developed stage
2/3 AKI and 25 (10.2%) developed persistent stage 2/3 AKI. Predicting stage 2/3
AKI revealed the optimal NGAL cutoffs in EDTA plasma (142.0 ng/mL), heparin
plasma (148.3 ng/mL) and urine (78.0 ng/mL) and yielded the following decision
statistics: sensitivity (SN)=78.8%, specificity (SP)=73.0%, positive predictive
value (PPV)=31.3%, negative predictive value (NPV)=95.7%, diagnostic accuracy
(DA)=73.8% (EDTA plasma); SN=72.7%, SP=73.8%, PPV=30.4%, NPV=94.5%, DA=73.7%
(heparin plasma); SN=69.7%, SP=76.8%, PPV=32.9%, NPV=94%, DA=75.8% (urine). The
optimal NGAL cutoffs to predict persistent stage 2/3 AKI were similar: 148.3
ng/mL (EDTA plasma), 169.6 ng/mL (heparin plasma) and 79.0 ng/mL (urine)
yielding: SN=84.0%, SP=73.5%, PPV=26.6%, NPV=97.6, DA=74.6% (EDTA plasma),
SN=84%, SP=76.1%, PPV=26.8%, NPV=96.5%, DA=76.1% (heparin plasma) and SN=75%,
SP=75.8%, PPV=26.1, NPV=96.4%, DA=75.7% (urine). CONCLUSION: Blood and urine NGAL
predicted stage 2/3 AKI, as well as persistent 2/3 AKI in the ICU with acceptable
decision statistics using a single cut point in each type of specimen.
PMID- 28698339
TI - Ethnic differences in current smoking and former smoking in the Netherlands and
the contribution of socioeconomic factors: a cross-sectional analysis of the
HELIUS study.
AB - OBJECTIVES: Data exploring how much of the ethnic differences in smoking
prevalence and former smoking are explained by socioeconomic status (SES) are
lacking. We therefore assessed ethnic differences in smoking prevalence and
former smoking and the contribution of both educational level and occupational
related SES to the observed ethnic differences in smoking behaviour. METHODS:
Data of 22 929 participants (aged 18-70 years) from the multiethnic cross
sectional Healthy Life in an Urban Setting study in the Netherlands were
analysed. Poisson regression models with a robust variance were used to estimate
prevalence ratios. RESULTS: Compared with the Dutch, after adjustment for age and
marital status, smoking prevalence was higher in men of Turkish (prevalence ratio
1.69, 95% CI 1.54 to 1.86), African Surinamese (1.55, 95% CI 1.41 to 1.69) and
South-Asian Surinamese origin (1.53, 95% CI 1.40 to 1.68), whereas among women,
smoking prevalence was higher in Turkish, similar in African Surinamese but lower
in all other ethnic origin groups. All ethnic minority groups, except Ghanaians,
had a significantly lower smoking cessation prevalence than the Dutch.
Socioeconomic gradients in smoking (higher prevalence among those lower educated
and with lower level employment) were observed in all groups except Ghanaian
women (a higher prevalence was observed in the higher educated). Ethnic
differences in smoking prevalence and former smoking are largely, but not
completely, explained by socioeconomic factors. CONCLUSIONS: Our findings imply
that antismoking policies designed to target smoking within the lower
socioeconomic groups of ethnic minority populations may substantially reduce
ethnic inequalities in smoking particularly among men and that certain groups may
benefit from targeted smoking cessation interventions.
PMID- 28698340
TI - Leisure-time physical activity and circulating 25-hydroxyvitamin D levels in
cancer survivors: a cross-sectional analysis using data from the US National
Health and Nutrition Examination Survey.
AB - OBJECTIVES: Circulating 25-hydroxyvitamin D (25-OHD) is associated with improved
cancer prognosis in some studies, yet it may be a surrogate marker for physical
activity. We investigated the associations of leisure-time physical activity
(LTPA) with circulating 25-OHD levels in cancer survivors, and determined whether
associations differ by indoor and outdoor activity. DESIGN: Cross-sectional
study. SETTING: The US National Health and Nutrition Examination Survey (NHANES).
PARTICIPANTS: Cancer survivors with available data on demographic information,
measures of adiposity, smoking history, self-reported LTPA and circulating 25-OHD
levels in five waves of NHANES (2001-2010). MAIN OUTCOMES MEASURES: Circulating
25-OHD levels. RESULTS: Multivariable linear regression and logistic regression
models were used to evaluate the associations of self-reported LTPA with 25-OHD,
adjusting for potential confounders. Due to the differences in LTPA measure, the
analyses were conducted separately for 2001-2006 and 2007-2010 data. We further
estimated associations by indoor and outdoor activity in the 2001-2006 data.
There were 1530 cancer survivors (mean age=60.5 years, mean body mass index=28.6
kg/m2). The prevalent cancer sites were breast (19.3%), prostate (18.8%), cervix
(10.4%) and colon (8.6%). Compared with inactive cancer survivors, being
physically active was associated with higher circulating 25-OHD levels (8.07
nmol/L, 95% CI 4.63 to 11.52) for 2001-2006 data. In the mutually adjusted model,
higher outdoor activity (5.83 nmol/L, 95% CI 1.64 to 10.01), but not indoor
activity (2.93 nmol/L, 95% CI -1.80 to 7.66), was associated with statistically
significantly higher 25-OHD levels. The interaction between indoor and outdoor
activities was, however, not significant (p=0.29). The only statistically
significant association seen in the 2007-2010 data was among obese cancer
survivors. CONCLUSION: Physical activity, particularly outdoor activity, is
associated with higher 25-OHD levels in cancer survivors. In view of the possible
beneficial effects of vitamin D on cancer prognosis, engaging in outdoor physical
activity could provide clinically meaningful increases in 25-OHD levels among
cancer survivors.
PMID- 28698341
TI - Sleeping pill use in Brazil: a population-based, cross-sectional study.
AB - OBJECTIVES: This study aimed to assess the prevalence of sleeping pill use in
Brazil. DESIGN: A population-based cross-sectional study with a three-stage
cluster sampling design (census tracts, households and adult residents) was used.
SETTING: The Brazilian 2013 National Health Survey was used. PARTICIPANTS: The
study population consisted of household residents aged >=18 years. A total of 60
202 individuals were interviewed, including 52.9% women, and 21% reported
depressive symptoms. OUTCOMES: The primary outcome was sleeping pill use, which
was self-reported with the question, 'Over the past two weeks, have you used any
sleeping pills?' The prevalence was calculated and stratified according to
sociodemographic characteristics. The associated factors were identified from
prevalence ratios (PRs) obtained through a Poisson regression with robust
variance and adjusted for sex and age. RESULTS: The prevalence of sleeping pill
use was 7.6% (95% CI 7.3% to 8.0%), and the average treatment duration was 9.75
(95% CI 9.49 to 10.00) days. Self-medication was found in 11.2% (95% CI 9.6% to
12.9%) of users. The following factors were associated with sleeping pill use:
female sex (PR=2.21; 95% CI 1.97 to 2.47), an age of >=60 years (PR=5.43; 95% CI
4.14 to 7.11) and smoking (PR=1.47; 95% CI 1.28 to 1.68). Sleeping pill use was
also positively associated with the severity of depressive symptoms (p<0.001),
whereas alcohol intake was inversely associated (PR=0.66; 95% CI 0.56 to 0.77).
CONCLUSIONS: One in every 13 Brazilians adults uses sleeping pills. There is a
lack of information about the reasons for this use. Actions are required to raise
awareness about the risks. The results could assist programmes in targeting
rational sleeping pill use and the identification of factors demanding
intervention.
PMID- 28698342
TI - Prevalence and antibiotic resistance of Mycoplasma genitalium among STI clinic
attendees in Western Canada: a cross-sectional analysis.
AB - OBJECTIVES: To determine the prevalence and correlates of Mycoplasma genitalium
(MG) infection among men and women, determine the prevalence of gene mutations
conferring resistance and compare test performance of female specimen types.
METHODS: A cross-sectional study was conducted on specimens collected for
gonorrhoea (NG, Neisseria gonorrhoeae) and chlamydia (CT, Chlamydia trachomatis)
among male and female Alberta STI clinic attendees using the M. genitalium
transcription-mediated amplification-research use only test. Positive specimens
were sequenced for 23SrRNA, parC and gyrA genes. Gender-stratified analysis
compared test results using chi2 or Fisher's exact test, Mann-Whitney U test and
logistic regression. Female endocervical and urine specimens were compared.
RESULTS: A total of 2254 individuals were tested; 53.8% (n=1212) were male. Male
prevalence of MG was 5.3%; CT was 5.9% and NG was 1.8%. Correlates of male
infection were a non-gonococcal urethritis diagnosis and NG coinfection. MG
prevalence for women was 7.2%; CT was 5.8% and NG was 1.8%. Correlates of female
infection were younger age, Indigenous/Other ethnicity and CT/NG coinfection.
Nearly two-thirds of eligible specimens had mutations associated with macrolide
resistance and 12.2% of specimens had a parC mutation signifying possible
moxifloxacin resistance. There was high concordance (98.1%) of results between
urine and endocervical swabs. CONCLUSIONS: The high prevalence of MG relative to
CT and NG supports the incorporation of MG testing into routine sexually
transmissible infection screening. The high rate of resistance to macrolides and
moxifloxacin raises concerns about treatment options. The good concordance of
results between urine and endocervical swabs supports the use of female urine
specimens for testing.
PMID- 28698343
TI - Protocol for an observational study of delirium in the post-anaesthesia care unit
(PACU) as a potential predictor of subsequent postoperative delirium.
AB - INTRODUCTION: Postoperative delirium can be a serious consequence of major
surgery, associated with longer hospital stays, readmission, cognitive and
functional deterioration and mortality. Delirium is an acute, reversible disorder
characterised by fluctuating course, inattention, disorganised thinking and
altered level of consciousness. Delirium occurring in the hours immediately
following anaesthesia and delirium occurring in the postoperative period of 1-5
days have been described as distinct clinical entities. This protocol describes
an observational study with the aim of determining if delirium in the first hour
following tracheal tube removal is a predictor of delirium in the 5 subsequent
postoperative days. Improved understanding regarding the development of
postoperative delirium would improve patient care and allow more effective
implementation of delirium prevention measures. METHODS AND ANALYSIS: Patients
enrolled to the Electroencephalography Guidance of Anesthesia to Alleviate
Geriatric Syndromes (ENGAGES) randomised controlled trial will be eligible for
this substudy. A validated delirium assessment method, the 3-min Diagnostic
Confusion Assessment Method and the Richmond Agitation and Sedation Scale will be
used to assess 100 patients for delirium at 30 min and 60 min following tracheal
tube removal. Patients will also be assessed for delirium over postoperative days
1-5 using three validated methods, the Confusion Assessment Method (CAM), CAM for
the Intensive Care Unit and structured chart review. Logistic regression analysis
will then be performed to test whether immediately postoperative delirium
independently predicts subsequent postoperative delirium. ETHICS AND
DISSEMINATION: This observational substudy of ENGAGES has been approved by the
ethics board of Washington University School of Medicine. Enrolment began in June
2016 and will continue until June 2017. Dissemination plans include presentations
at scientific conferences and scientific publications. TRIAL REGISTRATION NUMBER:
NCT02241655.
PMID- 28698344
TI - The involvement of physician assistants in inpatient care in hospitals in the
Netherlands: a cost-effectiveness analysis.
AB - OBJECTIVE: To investigate the cost-effectiveness of substitution of inpatient
care from medical doctors (MDs) to physician assistants (PAs). DESIGN: Cost
effectiveness analysis embedded within a multicentre, matched-controlled study.
The traditional model in which only MDs are employed for inpatient care (MD
model) was compared with a mixed model in which, besides MDs, PAs are also
employed (PA/MD model). SETTING: 34 hospital wards across the Netherlands.
PARTICIPANTS: 2292 patients were followed from admission until 1 month after
discharge. Patients receiving daycare, terminally ill patients and children were
excluded. PRIMARY AND SECONDARY OUTCOME MEASURES: All direct healthcare costs
from day of admission until 1 month after discharge. Health outcome concerned
quality-adjusted life years (QALYs), which was measured with the EuroQol five
dimensions questionnaire (EQ-5D). RESULTS: We found no significant difference for
QALY gain (+0.02, 95% CI -0.01 to 0.05) when comparing the PA/MD model with the
MD model. Total costs per patient did not significantly differ between the groups
(+?568, 95% CI -?254 to ?1391, p=0.175). Regarding the costs per item, a
difference of ?309 per patient (95% CI ?29 to ?588, p=0.030) was found in favour
of the MD model regarding length of stay. Personnel costs per patient for the
provider who is primarily responsible for medical care on the ward were lower on
the wards in the PA/MD model (-?11, 95% CI -?16 to -?6, p<0.01). CONCLUSIONS:
This study suggests that the cost-effectiveness on wards managed by PAs, in
collaboration with MDs, is similar to the care on wards with traditional house
staffing. The involvement of PAs may reduce personnel costs, but not overall
healthcare costs. TRIAL REGISTRATION NUMBER: NCT01835444.
PMID- 28698345
TI - Suboptimal vitamin D status in Korean adolescents: a nationwide study on its
prevalence, risk factors including cotinine-verified smoking status and
association with atopic dermatitis and asthma.
AB - OBJECTIVE: To determine the prevalence and risk factors for suboptimal vitamin D
status in Korean adolescents and to assess its relationship with atopic
dermatitis (AD) and asthma at a national level. DESIGN: This is a cross-sectional
study with data from the Korean National Health and Nutrition Examination Survey.
Information regarding socioeconomic characteristics, clinical data and
environmental factors was collected. Blood and urine samples were taken for
vitamin D and cotinine, respectively. Descriptive and multivariable logistic
regression was performed on the data. SETTING: South Korea (nationwide).
PARTICIPANTS: 2515 individuals aged 10-18 years who participated in the Korean
National Health and Nutrition Examination Survey from 2008 to 2011. MAIN OUTCOME
MEASURES: Vitamin D status was determined through measurement of serum 25
hydroxyvitamin D (25OHD). Smoking status was classified based on the urine
cotinine level. Physician diagnosed with AD and asthma were assessed using a
questionnaire. RESULTS: Overall, 73.3% of the subjects were vitamin D deficient
(25OHD <20 ng/mL) and 24.4% of the subjects were vitamin D insufficient (25OHD,
20-29.9 ng/mL). Older age (p<0.001), female gender (p<0.001), urban residence
(p=0.019), higher body mass index (p=0.003) and sampling in winter months
(November-March) (p<0.001) were independently associated with low serum 25OHD
levels. With cotinine verification, 18.2% of the participants were classified as
active smokers, and 43.4% were classified as passive smokers. After adjusting for
potential confounders, serum 25OHD status showed no association with AD or
asthma. CONCLUSION: Vitamin D deficiency is highly prevalent in Korean
adolescents. Cotinine-verified prevalence of smoking was also high, but its
relationship with vitamin D deficiency was not confirmed in our study. Above all,
our results provide epidemiological evidence against the association of vitamin D
status with AD and asthma at the national level among Korean adolescents.
PMID- 28698346
TI - Acute mountain sickness, arterial oxygen saturation and heart rate among Tibetan
students who reascend to Lhasa after 7 years at low altitude: a prospective
cohort study.
AB - OBJECTIVES: The aim of the present study was to estimate the incidence of acute
mountain sickness (AMS) and address the changes in arterial oxygen saturation
(SaO2) and heart rate (HR) in native Tibetans who reascend to the high-altitude
city of Lhasa (3658 m) after a 7-year stay at low altitude. METHODS: We followed
two cohorts of students aged 17-21 years (859 Native Tibetan and 801 Han
Chinese), travelling from lowland China until 3 days after their arrival in
highland city of Lhasa. Questionnaire information of the symptoms of AMS using
the Lake Louise Scoring System, resting SaO2 and HR were assessed both before
leaving the lowland and after arriving in Lhasa. Linear regression was performed
to compare changes in SaO2 and HR levels from low to high altitude in Tibetan and
Han Chinese. RESULTS: New cases of AMS occurred in only 1.2% (95% CI 0.4% to
2.0%) of the Tibetan students who came to Lhasa by train compared with 32.7% (95%
CI 28.0% to 37.3%) and 42.9% (95% CI 38.0% to 47.7%) of the Han Chinese students
who came to Lhasa by train and by air, respectively. Tibetan students had less
changes in SaO2 (-2.95 percentage points, 95% CI -3.24% to -2.65%) and HR (10.89
beats per minute (bpm), 95% CI 9.62 to 12.16 bpm) from low to high altitude
compared with Han Chinese students, although measurements did not differ between
the two groups when measured at low altitude. CONCLUSIONS: Healthy Tibetans are
mostly protected against AMS and primarily maintain their good adaptation to high
altitude, even after a long period of stay at low altitude.
PMID- 28698347
TI - CArbon dioxide surgical field flooding and aortic NO-touch off-pump coronary
artery bypass grafting to reduce Neurological injuries after surgical coronary
revascularisation (CANON): protocol for a randomised, controlled, investigator
and patient blinded single-centre superiority trial with three parallel arms.
AB - INTRODUCTION: Neurological injuries remain a major concern following coronary
artery bypass grafting (CABG) that offsets survival benefit of CABG over
percutaneous coronary interventions. Among numerous efforts to combat this issue
is the development of off-pump CABG (OPCABG) that obviates the need for
extracorporeal circulation and is associated with improved neurological outcomes.
The objective of this study is to examine whether the neuroprotective effect of
OPCABG can be further pronounced by the use of two state-of-the-art operating
techniques. METHODS AND ANALYSIS: In this randomised, controlled, investigator
and patient blinded single-centre superiority trial with three parallel arms, a
total of 360 patients will be recruited. They will be allocated in a 1:1:1 ratio
to two treatment arms and one control arm. Treatment arms undergoing either
aortic no-touch OPCABG or OPCABG with partial clamp applying carbon dioxide
surgical field flooding will be compared against control arm undergoing OPCABG
with partial clamp. The primary endpoint will be the appearance of new lesions on
control brain MRI 3 days after surgery. Secondary endpoints will include the
prevalence of new focal neurological deficits in the first 7 days after surgery,
the occurrence of postoperative cognitive dysfunction at either 1 week or 3
months after surgery and the incidence of delirium in the first 7 days after
surgery. Data will be analysed on intention-to-treat principles and a per
protocol basis. ETHICS AND DISSEMINATION: Ethical approval has been granted for
this study. Results will be disseminated through peer-reviewed media. TRIAL
REGISTRATION NUMBER: NCT03074604; Pre-results. DATE AND VERSION IDENTIFIER: 10
Mar-2017 Original.
PMID- 28698348
TI - Determinants of mortality and prolonged hospital stay among dengue patients
attending tertiary care hospital: a cross-sectional retrospective analysis.
AB - OBJECTIVES: Dengue imposes substantial economic, societal and personal burden in
terms of hospital stay, morbidity and mortality. Early identification of dengue
cases with high propensity of increased hospital stay and death could be of value
in isolating patients in need of early interventions. The current study was aimed
to determine the significant factors associated with dengue-related prolonged
hospitalisation and death. DESIGN: Cross-sectional retrospective study. SETTING:
Tertiary care teaching hospital. PARTICIPANTS: Patients with confirmed dengue
diagnosis were stratified into two categories on the basis of prolonged
hospitalisation (<=3 days and >3 days) and mortality (fatal cases and non-fatal
cases). Clinico-laboratory characteristics between these categories were compared
by using appropriate statistical methods. RESULTS: Of 667 patients enrolled, 328
(49.2%) had prolonged hospitalisation. The mean hospital stay was 4.88+/-2.74
days. Multivariate analysis showed that dengue haemorrhagic fever (OR 2.3),
elevated alkaline phosphatase (ALP) (OR 2.3), prolonged prothrombin time (PT) (OR
1.7), activated partial thromboplastin time (aPTT) (OR 1.9) and multiple-organ
dysfunctions (OR 2.1) were independently associated with prolonged
hospitalisation. Overall case fatality rate was 1.1%. Factors associated with
dengue mortality were age >40 years (p=0.004), secondary infection (p=0.040),
comorbidities (p<0.05), acute kidney injury (p<0.001), prolonged PT (p=0.022),
multiple-organ dysfunctions (p<0.001), haematocrit >20% (p=0.001), rhabdomyolosis
(p<0.001) and respiratory failure (p=0.007). Approximately half of the fatal
cases in our study had prolonged hospital stay of greater than three days.
CONCLUSIONS: The results underscore the high proportion of dengue patients with
prolonged hospital stay. Early identification of factors relating to prolonged
hospitalisation and death will have obvious advantages in terms of appropriate
decisions about treatment and management in high dependency units.
PMID- 28698349
TI - A pilot randomised controlled trial of a periodised resistance training and
protein supplementation intervention in prostate cancer survivors on androgen
deprivation therapy.
AB - INTRODUCTION: Prostate cancer survivors (PCS) receiving androgen deprivation
therapy (ADT) experience deleterious side effects such as unfavourable changes in
cardiometabolic factors that lead to sarcopenic obesity and metabolic syndrome
(MetS). While loss of lean body mass (LBM) compromises muscular strength and
quality of life, MetS increases the risk of cardiovascular disease and may
influence cancer recurrence. Exercise can improve LBM and strength, and may serve
as an alternative to the pharmacological management of MetS in PCS on ADT. Prior
exercise interventions in PCS on ADT have been effective at enhancing strength,
but only marginally effective at enhancing body composition and ameliorating
cardiometabolic risk factors. This pilot trial aims to improve on existing
interventions by employing periodised resistance training (RT) to counter
sarcopenic obesity in PCS on ADT. Secondary aims compare intervention effects on
cardiometabolic, physical function, quality of life and molecular skeletal muscle
changes. An exploratory aim examines if protein supplementation (PS) in
combination with RT elicits greater changes in these outcomes. METHODS AND
ANALYSIS: A 2*2 experimental design is used in 32 PCS on ADT across a 12-week
intervention period. Participants are randomised to resistance training and
protein supplementation (RTPS), RT, PS or control. RT and RTPS groups perform
supervised RT three times per week for 12 weeks, while PS and RTPS groups receive
50 g whey protein per day. This pilot intervention applies a multilayered
approach to ameliorate detrimental cardiometabolic effects of ADT while
investigating molecular mechanisms underlying skeletal muscle changes in PCS.
ETHICS AND DISSEMINATION: This trial was approved by the University of Southern
California Institutional Review Board (HS-13-00315). Results from this trial will
be communicated in peer-reviewed publications and scientific presentations. TRIAL
REGISTRATION NUMBER: NCT01909440; Pre-results.
PMID- 28698350
TI - Efficacy of nanocurcumin supplementation on insulin resistance, lipids,
inflammatory factors and nesfatin among obese patients with non-alcoholic fatty
liver disease (NAFLD): a trial protocol.
AB - OBJECTIVES: Different studies have been conducted on the role of curcumin in
health since having multiple properties, including antioxidant and anti
inflammatory effects. Due to the lack of studies regarding curcumin effects on
obese patients with non-alcoholic fatty liver disease (NAFLD), our protocol was
designed to assess nanocurcumin impacts on blood sugar, lipids, inflammatory
indices, insulin resistance and liver function, especially by nesfatin. SETTING:
This trial will be conducted in the Oil Company central hospital of Tehran, Iran
with a primary level of care. PARTICIPANTS: 84 obese patients with NAFLD
diagnosed using ultrasonography will be employed according to the eligibility
criteria. INTERVENTIONS: The patients will be randomly divided into two equal
groups (nanocurcumin and placebo, two 40 mg capsules per day with meals for 3
months, follow-up monthly). Also, lifestyle changes (low-calorie diet and
physical activity) will be advised. MEASURES OF THE PRIMARY AND SECONDARY
OUTCOMES: A general questionnaire, 24 hours food recall (at the beginning, middle
and end) and short-form International Physical Activity Questionnaire will be
completed. Blood pressure, anthropometrics, serum sugar indices (fasting blood
sugar and insulin, insulin resistance and sensitivity and glycosylated
haemoglobin), lipids (triglyceride, total cholesterol and low-density and high
density lipoprotein-cholesterol, inflammatory profiles (interleukin-6, high
sensitivity C-reactive protein, and tumour necrosis factor-alpha), liver function
(alanine and aspartate transaminase) and nesfatin will be measured at the
beginning and end of the study. CONCLUSION: This trial would be the first
experiment to determine nanocurcumin efficacy on certain blood factors among
obese patients with NAFLD. Nevertheless, studying the potential consequences of
curcumin in various diseases, especially NAFLD, is required for clinical use.
TRIAL REGISTRATION NUMBER: IRCT2016071915536N3; pre-results.
PMID- 28698351
TI - Subdissociative intranasal ketamine plus standard pain therapy versus standard
pain therapy in the treatment of paediatric sickle cell disease vaso-occlusive
crises in resource-limited settings: study protocol for a randomised controlled
trial.
AB - INTRODUCTION: Pediatric sickle cell disease, highly prevalent in sub-Saharan
Africa, carries great morbidity and mortality risk. Limited resources and
monitoring make management of acute vaso-occlusive crises challenging. This study
aims to evaluate the efficacy and safety of subdissociative intranasal ketamine
as a cheap, readily available and easily administered adjunct to standard pain
therapy. We hypothesise that subdissociative, intranasal ketamine may
significantly augment current approaches to pain management in resource-limited
settings in a safe and cost-effective manner. METHODS AND ANALYSIS: This is a
multicentred, randomised, double-blind, placebo-controlled trial enrolling
children 4-16 years of age with sickle cell disease and painful vaso-occlusive
pain crises. Study sites include two sub-Saharan teaching and referral hospitals
with acute intake areas. All patients receive standard analgesic therapy during
evaluation. Patients randomised to the treatment arm receive 1 mg/kg intranasal
ketamine at onset of therapy, while placebo arm participants receive volume
matched intranasal normal saline. All participants and clinical staff are blinded
to the treatment allocation. Data will be analysed on an intention-to-treat
basis. Primary endpoints are changes in self-report pain scales (Faces Pain Scale
Revised) at 30, 60 and 120 minutes and rates of adverse events. Secondary
endpoints include hospital length of stay, total analgesia use and quality of
life assessment 2-3 weeks postintervention. ETHICS AND DISSEMINATION: The
research methods for this study have been approved by the Cameroon Baptist
Convention Health Board Institutional Review Board (IRB2015-07), the Tanzanian
National Institute for Medical Research (NIMR/HQ/R.8a/Vol. IX/2299), Muhimbili
National Hospital IRB (MNH/IRB/I/2015/14) and the Tanzanian Food and Drugs
Authority (TFDA0015/CTR/0015/9). Data reports will be provided to the Data and
Safety Monitoring Board (DSMB) periodically throughout the study as well as all
reports of adverse events. All protocol amendments will also be reviewed by the
DSMB. Study results, regardless of direction or amplitude, will be submitted for
publication in relevant peer-reviewed journals. TRIAL REGISTRATION:
ClinicalTrials.Gov, NCT02573714. Date of registration: 8 October 2015. Pre
results.
PMID- 28698352
TI - Frequency and preventative interventions for non-suicidal self-injury and
suicidal behaviour in primary school-age children: a scoping review protocol.
AB - INTRODUCTION: Non-suicidal self-injury (NSSI) and suicidal behaviour have been
witnessed in children as young as 6-7 years of age, but while there are many
reviews of preventative interventions for NSSI and suicide in adolescents, few
have explored its prevalence in younger children and the potential impact of
preventative interventions at this stage of life. NSSI and suicidal behaviour are
an increasing concern in schools but school-based programmes can improve
knowledge, attitudes and help-seeking behaviours and help prevent escalation of
NSSI and later suicide. This scoping review will aim to explore the nature and
extent of the evidence on the magnitude of NSSI and suicidal behaviour in primary
school children, and to examine whether there are any primary school-based
interventions available for the prevention of this phenomenon in 5 to 11-year
olds. METHODS AND ANALYSIS: A scoping review will be conducted using established
methodology by Arksey and O'Malley and the Joanna Briggs Institute. Multiple
bibliographic and indexing databases and grey literature will be searched using a
combination of text words and index terms relating to NSSI, suicide, primary
schools, frequency and intervention. Two reviewers will independently screen
eligible studies for study selection and extract relevant data from included
studies. A narrative summary of evidence will be conducted for all included
studies with results presented in tables and/or diagrams. Inductive content
analysis will be used to understand any narrative findings within the included
studies. ETHICS AND DISSEMINATION: Ethical approval is not required for this
scoping review. The results of this review will be disseminated though
publication in a peer-reviewed journal and presented at relevant conferences.
PMID- 28698353
TI - Correction: The association between human herpesvirus infections and stroke: a
systematic review protocol.
PMID- 28698354
TI - Enhanced Secondary- and Hormone Metabolism in Leaves of Arbuscular Mycorrhizal
Medicago truncatula.
AB - Arbuscular mycorrhizas (AM) are the most common symbiotic associations between a
plant's root compartment and fungi. They provide nutritional benefit (mostly
inorganic phosphate [Pi]), leading to improved growth, and nonnutritional
benefits, including defense responses to environmental cues throughout the host
plant, which, in return, delivers carbohydrates to the symbiont. However, how
transcriptional and metabolic changes occurring in leaves of AM plants differ
from those induced by Pi fertilization is poorly understood. We investigated
systemic changes in the leaves of mycorrhized Medicago truncatula in conditions
with no improved Pi status and compared them with those induced by high-Pi
treatment in nonmycorrhized plants. Microarray-based genome-wide profiling
indicated up-regulation by mycorrhization of genes involved in flavonoid,
terpenoid, jasmonic acid (JA), and abscisic acid (ABA) biosynthesis as well as
enhanced expression of MYC2, the master regulator of JA-dependent responses.
Accordingly, total anthocyanins and flavonoids increased, and most flavonoid
species were enriched in AM leaves. Both the AM and Pi treatments corepressed
iron homeostasis genes, resulting in lower levels of available iron in leaves. In
addition, higher levels of cytokinins were found in leaves of AM- and Pi-treated
plants, whereas the level of ABA was increased specifically in AM leaves. Foliar
treatment of nonmycorrhized plants with either ABA or JA induced the up
regulation of MYC2, but only JA also induced the up-regulation of flavonoid and
terpenoid biosynthetic genes. Based on these results, we propose that
mycorrhization and Pi fertilization share cytokinin-mediated improved shoot
growth, whereas enhanced ABA biosynthesis and JA-regulated flavonoid and
terpenoid biosynthesis in leaves are specific to mycorrhization.
PMID- 28698355
TI - Tissue-Specific Control of the Endocycle by the Anaphase Promoting
Complex/Cyclosome Inhibitors UVI4 and DEL1.
AB - The endocycle represents a modified mitotic cell cycle that in plants is often
coupled to cell enlargement and differentiation. Endocycle onset is controlled by
activity of the Anaphase Promoting Complex/Cyclosome (APC/C), a multisubunit E3
ubiquitin ligase targeting cell-cycle factors for destruction. CELL CYCLE
SWITCH52 (CCS52) proteins represent rate-limiting activator subunits of the
APC/C. In Arabidopsis (Arabidopsis thaliana), mutations in either CCS52A1 or
CCS52A2 activators result in a delayed endocycle onset, whereas their
overexpression triggers increased DNA ploidy levels. Here, the relative
contribution of the APC/CCCS52A1 and APC/CCCS52A2 complexes to different
developmental processes was studied through analysis of their negative
regulators, being the ULTRAVIOLET-B-INSENSITIVE4 protein and the DP-E2F-Like1
transcriptional repressor, respectively. Our data illustrate cooperative activity
of the APC/CCCS52A1 and APC/CCCS52A2 complexes during root and trichome
development, but functional interdependency during leaf development. Furthermore,
we found APC/CCCS52A1 activity to control CCS52A2 expression. We conclude that
interdependency of CCS52A-controlled APC/C activity is controlled in a tissue
specific manner.
PMID- 28698356
TI - Root Bending Is Antagonistically Affected by Hypoxia and ERF-Mediated
Transcription via Auxin Signaling.
AB - When plants encounter soil water logging or flooding, roots are the first organs
to be confronted with reduced gas diffusion resulting in limited oxygen supply.
Since roots do not generate photosynthetic oxygen, they are rapidly faced with
oxygen shortage rendering roots particularly prone to damage. While metabolic
adaptations to low oxygen conditions, which ensure basic energy supply, have been
well characterized, adaptation of root growth and development have received less
attention. In this study, we show that hypoxic conditions cause the primary root
to grow sidewise in a low oxygen environment, possibly to escape soil patches
with reduced oxygen availability. This growth behavior is reversible in that
gravitropic growth resumes when seedlings are returned to normoxic conditions.
Hypoxic root bending is inhibited by the group VII ethylene response factor
(ERFVII) RAP2.12, as rap2.12-1 seedlings show exaggerated primary root bending.
Furthermore, overexpression of the ERFVII member HRE2 inhibits root bending,
suggesting that primary root growth direction at hypoxic conditions is
antagonistically regulated by hypoxia and hypoxia-activated ERFVIIs. Root bending
is preceded by the establishment of an auxin gradient across the root tip as
quantified with DII-VENUS and is synergistically enhanced by hypoxia and the
auxin transport inhibitor naphthylphthalamic acid. The protein abundance of the
auxin efflux carrier PIN2 is reduced at hypoxic conditions, a response that is
suppressed by RAP2.12 overexpression, suggesting antagonistic control of auxin
flux by hypoxia and ERFVII. Taken together, we show that hypoxia triggers an
escape response of the primary root that is controlled by ERFVII activity and
mediated by auxin signaling in the root tip.
PMID- 28698357
TI - RopGEF1 Plays a Critical Role in Polar Auxin Transport in Early Development.
AB - Polar auxin transport, facilitated by the combined activities of auxin influx and
efflux carriers to maintain asymmetric auxin distribution, is essential for plant
growth and development. Here, we show that Arabidopsis (Arabidopsis thaliana)
RopGEF1, a guanine nucleotide exchange factor and activator of Rho GTPases of
plants (ROPs), is critically involved in polar distribution of auxin influx
carrier AUX1 and differential accumulation of efflux carriers PIN7 and PIN2 and
is important for embryo and early seedling development when RopGEF1 is
prevalently expressed. Knockdown or knockout of RopGEF1 induces embryo defects,
cotyledon vein breaks, and delayed root gravity responses. Altered expression
from the auxin response reporter DR5rev:GFP in the root pole of RopGEF1-deficient
embryos and loss of asymmetric distribution of DR5rev:GFP in their
gravistimulated root tips suggest that auxin distribution is affected in ropgef1
mutants. This is reflected by the polarity of AUX1 being altered in ropgef1
embryos and roots, shifting from the normal apical membrane location to a basal
location in embryo central vascular and root protophloem cells and also reduced
PIN7 accumulation at embryos and altered PIN2 distribution in gravistimulated
roots of mutant seedlings. In establishing that RopGEF1 is critical for AUX1
localization and PIN differential accumulation, our results reveal a role for
RopGEF1 in cell polarity and polar auxin transport whereby it imapcts auxin
mediated plant growth and development.
PMID- 28698358
TI - Integrative CAGE and DNA Methylation Profiling Identify Epigenetically Regulated
Genes in NSCLC.
AB - Lung cancer is the leading cause of cancer-related deaths worldwide. The majority
of cancer driver mutations have been identified; however, relevant epigenetic
regulation involved in tumorigenesis has only been fragmentarily analyzed.
Epigenetically regulated genes have a great theranostic potential, especially in
tumors with no apparent driver mutations. Here, epigenetically regulated genes
were identified in lung cancer by an integrative analysis of promoter-level
expression profiles from Cap Analysis of Gene Expression (CAGE) of 16 non-small
cell lung cancer (NSCLC) cell lines and 16 normal lung primary cell specimens
with DNA methylation data of 69 NSCLC cell lines and 6 normal lung epithelial
cells. A core set of 49 coding genes and 10 long noncoding RNAs (lncRNA), which
are upregulated in NSCLC cell lines due to promoter hypomethylation, was
uncovered. Twenty-two epigenetically regulated genes were validated (upregulated
genes with hypomethylated promoters) in the adenocarcinoma and squamous cell
cancer subtypes of lung cancer using The Cancer Genome Atlas data. Furthermore,
it was demonstrated that multiple copies of the REP522 DNA repeat family are
prominently upregulated due to hypomethylation in NSCLC cell lines, which leads
to cancer-specific expression of lncRNAs, such as RP1-90G24.10, AL022344.4, and
PCAT7. Finally, Myeloma Overexpressed (MYEOV) was identified as the most
promising candidate. Functional studies demonstrated that MYEOV promotes cell
proliferation, survival, and invasion. Moreover, high MYEOV expression levels
were associated with poor prognosis.Implications: This report identifies a robust
list of 22 candidate driver genes that are epigenetically regulated in lung
cancer; such genes may complement the known mutational drivers.Visual Overview:
http://mcr.aacrjournals.org/content/molcanres/15/10/1354/F1.large.jpg Mol Cancer
Res; 15(10); 1354-65. (c)2017 AACR.
PMID- 28698359
TI - EGFR Downregulation after Anti-EGFR Therapy Predicts the Antitumor Effect in
Colorectal Cancer.
AB - Anti-EGFR mAb is reported to induce EGFR internalization in colorectal cancer
cells. However, the biological relevance of EGFR internalization with anti-EGFR
mAb is unknown. Therefore, the relevance of EGFR downregulation with anti-EGFR
mAb to antitumor activity in colorectal cancer cells was investigated.
Quantification of EGFR on the cell surface before cetuximab treatment was
assessed by flow cytometry, and its growth-inhibitory effects were measured by
Trypan blue exclusion, in 10 RAS, BRAF wild-type colorectal cancer cell lines,
but there was no significant correlation between EGFR number and its growth
inhibitory effect. However, a significant correlation existed between the
percentage decrease in the number of EGFRs after cetuximab treatment and its
growth-inhibitory effect in those cell lines. Treatment with TGFalpha, a ligand
for EGFR, induced EGFR internalization in colorectal cancer cells, but most EGFRs
subsequently recycled to the cell surface, consistent with previous studies.
While cetuximab treatment induced EGFR internalization, most receptors
subsequently translocated into the late endosome, leading to lysosomal
degradation, as revealed by immunoblotting and double immunofluorescence.
Cetuximab-sensitive colorectal cancer cells showed greater EGFR internalization,
stronger cell growth inhibition, and more augmented apoptotic signals than
nonsensitive cells. IHC for EGFR, performed using an EGFR pharmDx Kit (mouse anti
human EGFR mAb clone 2-18C9), in clinical specimens before and after anti-EGFR
mAb therapy in 13 colorectal cancer patients showed a significant correlation
between the response to anti-EGFR mAb and decreased staining after
therapy.Implications: This report clearly demonstrates that anti-EGFR mAb
facilitates internalization and subsequent degradation of EGFRs in lysosomes,
which is an important determinant of the efficacy of anti-EGFR mAb treatment for
colorectal cancer. Mol Cancer Res; 15(10); 1445-54. (c)2017 AACR.
PMID- 28698360
TI - Five minutes with . . . Steve Kell.
PMID- 28698361
TI - Profile of Stephen C. West.
PMID- 28698362
TI - Structural insights into lipoprotein N-acylation by Escherichia coli
apolipoprotein N-acyltransferase.
AB - Gram-negative bacteria express a diverse array of lipoproteins that are essential
for various aspects of cell growth and virulence, including nutrient uptake,
signal transduction, adhesion, conjugation, sporulation, and outer membrane
protein folding. Lipoprotein maturation requires the sequential activity of three
enzymes that are embedded in the cytoplasmic membrane. First,
phosphatidylglycerol:prolipoprotein diacylglyceryl transferase (Lgt) recognizes a
conserved lipobox motif within the prolipoprotein signal sequence and catalyzes
the addition of diacylglycerol to an invariant cysteine. The signal sequence is
then cleaved by signal peptidase II (LspA) to give an N-terminal S-diacylglyceryl
cysteine. Finally, apolipoprotein N-acyltransferase (Lnt) catalyzes the transfer
of the sn-1-acyl chain of phosphatidylethanolamine to this N-terminal cysteine,
generating a mature, triacylated lipoprotein. Although structural studies of Lgt
and LspA have yielded significant mechanistic insights into this essential
biosynthetic pathway, the structure of Lnt has remained elusive. Here, we present
crystal structures of wild-type and an active-site mutant of Escherichia coli
Lnt. The structures reveal a monomeric eight-transmembrane helix fold that
supports a periplasmic carbon-nitrogen hydrolase domain containing a Cys-Glu-Lys
catalytic triad. Two lipids are bound at the active site in the structures, and
we propose a putative phosphate recognition site where a chloride ion is
coordinated near the active site. Based on these structures and complementary
cell-based, biochemical, and molecular dynamics approaches, we propose a
mechanism for substrate engagement and catalysis by E. coli Lnt.
PMID- 28698363
TI - Corticogeniculate feedback sharpens the temporal precision and spatial resolution
of visual signals in the ferret.
AB - The corticogeniculate (CG) pathway connects the visual cortex with the visual
thalamus (LGN) in the feedback direction and enables the cortex to directly
influence its own input. Despite numerous investigations, the role of this
feedback circuit in visual perception remained elusive. To probe the function of
CG feedback in a causal manner, we selectively and reversibly manipulated the
activity of CG neurons in anesthetized ferrets in vivo using a combined viral
infection and optogenetics approach to drive expression of channelrhodopsin2
(ChR2) in CG neurons. We observed significant increases in temporal precision and
spatial resolution of LGN neuronal responses to drifting grating and white noise
stimuli when CG neurons expressing ChR2 were light activated. Enhancing CG
feedback reduced visually evoked response latencies, increased spike-timing
precision, and reduced classical receptive field size. Increased precision among
LGN neurons led to increased spike-timing precision among granular layer V1
neurons as well. Together, our findings suggest that the function of CG feedback
is to control the timing and precision of thalamic responses to incoming visual
signals.
PMID- 28698364
TI - Loss of mouse cardiomyocyte talin-1 and talin-2 leads to beta-1 integrin
reduction, costameric instability, and dilated cardiomyopathy.
AB - Continuous contraction-relaxation cycles of the heart require strong and stable
connections of cardiac myocytes (CMs) with the extracellular matrix (ECM) to
preserve sarcolemmal integrity. CM attachment to the ECM is mediated by integrin
complexes localized at the muscle adhesion sites termed costameres. The
ubiquitously expressed cytoskeletal protein talin (Tln) is a component of muscle
costameres that links integrins ultimately to the sarcomere. There are two talin
genes, Tln1 and Tln2. Here, we tested the function of these two Tln forms in
myocardium where Tln2 is the dominant isoform in postnatal CMs. Surprisingly,
global deletion of Tln2 in mice caused no structural or functional changes in
heart, presumably because CM Tln1 became up-regulated. Tln2 loss increased
integrin activation, although levels of the muscle-specific beta1D-integrin
isoform were reduced by 50%. With this result, we produced mice that had
simultaneous loss of both CM Tln1 and Tln2 and found that cardiac dysfunction
occurred by 4 wk with 100% mortality by 6 mo. beta1D integrin and other
costameric proteins were lost from the CMs, and membrane integrity was
compromised. Given that integrin protein reduction occurred with Tln loss, rescue
of the phenotype was attempted through transgenic integrin overexpression, but
this could not restore WT CM integrin levels nor improve heart function. Our
results show that CM Tln2 is essential for proper beta1D-integrin expression and
that Tln1 can substitute for Tln2 in preserving heart function, but that loss of
all Tln forms from the heart-muscle cell leads to myocyte instability and a
dilated cardiomyopathy.
PMID- 28698365
TI - Stable membrane orientations of small dual-topology membrane proteins.
AB - The topologies of alpha-helical membrane proteins are generally thought to be
determined during their cotranslational insertion into the membrane. It is
typically assumed that membrane topologies remain static after this process has
ended. Recent findings, however, question this static view by suggesting that
some parts of, or even the whole protein, can reorient in the membrane on a
biologically relevant time scale. Here, we focus on antiparallel homo- or
heterodimeric small multidrug resistance proteins and examine whether the
individual monomers can undergo reversible topological inversion (flip flop) in
the membrane until they are trapped in a fixed orientation by dimerization. By
perturbing dimerization using various means, we show that the membrane
orientation of a monomer is unaffected by the presence or absence of its
dimerization partner. Thus, membrane-inserted monomers attain their final
orientations independently of dimerization, suggesting that wholesale topological
inversion is an unlikely event in vivo.
PMID- 28698366
TI - NLR network mediates immunity to diverse plant pathogens.
AB - Both plants and animals rely on nucleotide-binding domain and leucine-rich repeat
containing (NLR) proteins to respond to invading pathogens and activate immune
responses. An emerging concept of NLR function is that "sensor" NLR proteins are
paired with "helper" NLRs to mediate immune signaling. However, our fundamental
knowledge of sensor/helper NLRs in plants remains limited. In this study, we
discovered a complex NLR immune network in which helper NLRs in the NRC (NLR
required for cell death) family are functionally redundant but display distinct
specificities toward different sensor NLRs that confer immunity to oomycetes,
bacteria, viruses, nematodes, and insects. The helper NLR NRC4 is required for
the function of several sensor NLRs, including Rpi-blb2, Mi-1.2, and R1, whereas
NRC2 and NRC3 are required for the function of the sensor NLR Prf. Interestingly,
NRC2, NRC3, and NRC4 redundantly contribute to the immunity mediated by other
sensor NLRs, including Rx, Bs2, R8, and Sw5. NRC family and NRC-dependent NLRs
are phylogenetically related and cluster into a well-supported superclade. Using
extensive phylogenetic analysis, we discovered that the NRC superclade probably
emerged over 100 Mya from an NLR pair that diversified to constitute up to one
half of the NLRs of asterids. These findings reveal a complex genetic network of
NLRs and point to a link between evolutionary history and the mechanism of immune
signaling. We propose that this NLR network increases the robustness of immune
signaling to counteract rapidly evolving plant pathogens.
PMID- 28698367
TI - Structure of the Arabidopsis TOPLESS corepressor provides insight into the
evolution of transcriptional repression.
AB - Transcriptional repression involves a class of proteins called corepressors that
link transcription factors to chromatin remodeling complexes. In plants such as
Arabidopsis thaliana, the most prominent corepressor is TOPLESS (TPL), which
plays a key role in hormone signaling and development. Here we present the
crystallographic structure of the Arabidopsis TPL N-terminal region comprising
the LisH and CTLH (C-terminal to LisH) domains and a newly identified third
region, which corresponds to a CRA domain. Comparing the structure of TPL with
the mammalian TBL1, which shares a similar domain structure and performs a
parallel corepressor function, revealed that the plant TPLs have evolved a new
tetramerization interface and unique and highly conserved surface for interaction
with repressors. Using site-directed mutagenesis, we validated those surfaces in
vitro and in vivo and showed that TPL tetramerization and repressor binding are
interdependent. Our results illustrate how evolution used a common set of protein
domains to create a diversity of corepressors, achieving similar properties with
different molecular solutions.
PMID- 28698368
TI - Microscopic dynamics of charge separation at the aqueous electrochemical
interface.
AB - We have used molecular simulation and methods of importance sampling to study the
thermodynamics and kinetics of ionic charge separation at a liquid water-metal
interface. We have considered this process using canonical examples of two
different classes of ions: a simple alkali-halide pair, Na+I-, or classical ions,
and the products of water autoionization, H3O+OH-, or water ions. We find that
for both ion classes, the microscopic mechanism of charge separation, including
water's collective role in the process, is conserved between the bulk liquid and
the electrode interface. However, the thermodynamic and kinetic details of the
process differ between these two environments in a way that depends on ion type.
In the case of the classical ion pairs, a higher free-energy barrier to charge
separation and a smaller flux over that barrier at the interface result in a rate
of dissociation that is 40 times slower relative to the bulk. For water ions, a
slightly higher free-energy barrier is offset by a higher flux over the barrier
from longer lived hydrogen-bonding patterns at the interface, resulting in a rate
of association that is similar both at and away from the interface. We find that
these differences in rates and stabilities of charge separation are due to the
altered ability of water to solvate and reorganize in the vicinity of the metal
interface.
PMID- 28698369
TI - A distinct subpopulation of CD25- T-follicular regulatory cells localizes in the
germinal centers.
AB - T-follicular helper (Tfh) cells differentiate through a multistep process,
culminating in germinal center (GC) localized GC-Tfh cells that provide support
to GC-B cells. T-follicular regulatory (Tfr) cells have critical roles in the
control of Tfh cells and GC formation. Although Tfh-cell differentiation is
inhibited by IL-2, regulatory T (Treg) cell differentiation and survival depend
on it. Here, we describe a CD25- subpopulation within both murine and human
PD1+CXCR5+Foxp3+ Tfr cells. It is preferentially located in the GC and can be
clearly differentiated from CD25+ non-GC-Tfr, Tfh, and effector Treg (eTreg)
cells by the expression of a wide range of molecules. In comparison to CD25+ Tfr
and eTreg cells, CD25- Tfr cells partially down-regulate IL-2-dependent canonical
Treg features, but retain suppressive function, while simultaneously up
regulating genes associated with Tfh and GC-Tfh cells. We suggest that, similar
to Tfh cells, Tfr cells follow a differentiation pathway generating a mature GC
localized subpopulation, CD25- Tfr cells.
PMID- 28698370
TI - G9a coordinates with the RPA complex to promote DNA damage repair and cell
survival.
AB - Histone methyltransferase G9a has critical roles in promoting cancer-cell growth
and gene suppression, but whether it is also associated with the DNA damage
response is rarely studied. Here, we report that loss of G9a impairs DNA damage
repair and enhances the sensitivity of cancer cells to radiation and
chemotherapeutics. In response to DNA double-strand breaks (DSBs), G9a is
phosphorylated at serine 211 by casein kinase 2 (CK2) and recruited to chromatin.
The chromatin-enriched G9a can then directly interact with replication protein A
(RPA) and promote loading of the RPA and Rad51 recombinase to DSBs. This
mechanism facilitates homologous recombination (HR) and cell survival. We
confirmed the interaction between RPA and G9a to be critical for RPA foci
formation and HR upon DNA damage. Collectively, our findings demonstrate a
regulatory pathway based on CK2-G9a-RPA that permits HR in cancer cells and
provide further rationale for the use of G9a inhibitors as a cancer therapeutic.
PMID- 28698371
TI - Deletion of Gas2l3 in mice leads to specific defects in cardiomyocyte cytokinesis
during development.
AB - GAS2L3 is a recently identified cytoskeleton-associated protein that interacts
with actin filaments and tubulin. The in vivo function of GAS2L3 in mammals
remains unknown. Here, we show that mice deficient in GAS2L3 die shortly after
birth because of heart failure. Mammalian cardiomyocytes lose the ability to
proliferate shortly after birth, and further increase in cardiac mass is achieved
by hypertrophy. The proliferation arrest of cardiomyocytes is accompanied by
binucleation through incomplete cytokinesis. We observed that GAS2L3 deficiency
leads to inhibition of cardiomyocyte proliferation and to cardiomyocyte
hypertrophy during embryonic development. Cardiomyocyte-specific deletion of
GAS2L3 confirmed that the phenotype results from the loss of GAS2L3 in
cardiomyocytes. Cardiomyocytes from Gas2l3-deficient mice exhibit increased
expression of a p53-transcriptional program including the cell cycle inhibitor
p21. Furthermore, loss of GAS2L3 results in premature binucleation of
cardiomyocytes accompanied by unresolved midbody structures. Together these
results suggest that GAS2L3 plays a specific role in cardiomyocyte cytokinesis
and proliferation during heart development.
PMID- 28698372
TI - Crystal structure of CO-bound cytochrome c oxidase determined by serial
femtosecond X-ray crystallography at room temperature.
AB - Cytochrome c oxidase (CcO), the terminal enzyme in the electron transfer chain,
translocates protons across the inner mitochondrial membrane by harnessing the
free energy generated by the reduction of oxygen to water. Several redox-coupled
proton translocation mechanisms have been proposed, but they lack confirmation,
in part from the absence of reliable structural information due to radiation
damage artifacts caused by the intense synchrotron radiation. Here we report the
room temperature, neutral pH (6.8), damage-free structure of bovine CcO (bCcO) in
the carbon monoxide (CO)-bound state at a resolution of 2.3 A, obtained by serial
femtosecond X-ray crystallography (SFX) with an X-ray free electron laser. As a
comparison, an equivalent structure was obtained at a resolution of 1.95 A, from
data collected at a synchrotron light source. In the SFX structure, the CO is
coordinated to the heme a3 iron atom, with a bent Fe-C-O angle of ~142 degrees .
In contrast, in the synchrotron structure, the Fe-CO bond is cleaved; CO
relocates to a new site near CuB, which, in turn, moves closer to the heme a3
iron by ~0.38 A. Structural comparison reveals that ligand binding to the heme a3
iron in the SFX structure is associated with an allosteric structural transition,
involving partial unwinding of the helix-X between heme a and a3, thereby
establishing a communication linkage between the two heme groups, setting the
stage for proton translocation during the ensuing redox chemistry.
PMID- 28698373
TI - Genetic identification of a hindbrain nucleus essential for innate vocalization.
AB - Vocalization in young mice is an innate response to isolation or mechanical
stimulation. Neuronal circuits that control vocalization and breathing overlap
and rely on motor neurons that innervate laryngeal and expiratory muscles, but
the brain center that coordinates these motor neurons has not been identified.
Here, we show that the hindbrain nucleus tractus solitarius (NTS) is essential
for vocalization in mice. By generating genetically modified newborn mice that
specifically lack excitatory NTS neurons, we show that they are both mute and
unable to produce the expiratory drive required for vocalization. Furthermore,
the muteness of these newborns results in maternal neglect. We also show that
neurons of the NTS directly connect to and entrain the activity of spinal (L1)
and nucleus ambiguus motor pools located at positions where expiratory and
laryngeal motor neurons reside. These motor neurons control expiratory pressure
and laryngeal tension, respectively, thereby establishing the essential
biomechanical parameters used for vocalization. In summary, our work demonstrates
that the NTS is an obligatory component of the neuronal circuitry that transforms
breaths into calls.
PMID- 28698374
TI - Bifunctionality of a biofilm matrix protein controlled by redox state.
AB - Biofilms are communities of microbial cells that are encapsulated within a self
produced polymeric matrix. The matrix is critical to the success of biofilms in
diverse habitats; however, many details of the composition, structure, and
function remain enigmatic. Biofilms formed by the Gram-positive bacterium
Bacillus subtilis depend on the production of the secreted film-forming protein
BslA. Here, we show that a gradient of electron acceptor availability through the
depth of the biofilm gives rise to two distinct functional roles for BslA and
that these roles can be genetically separated through targeted amino acid
substitutions. We establish that monomeric BslA is necessary and sufficient to
give rise to complex biofilm architecture, whereas dimerization of BslA is
required to render the community hydrophobic. Dimerization of BslA, mediated by
disulfide bond formation, depends on two conserved cysteine residues located in
the C-terminal region. Our findings demonstrate that bacteria have evolved
multiple uses for limited elements in the matrix, allowing for alternative
responses in a complex, changing environment.
PMID- 28698375
TI - BMTP-11 is active in preclinical models of human osteosarcoma and a candidate
targeted drug for clinical translation.
AB - Osteosarcoma occurs predominantly in children and young adults. High-grade tumors
require multidisciplinary treatment consisting of chemotherapy in the neoadjuvant
and adjuvant settings, along with surgical intervention. Despite this approach,
death from respiratory failure secondary to the development and progression of
pulmonary metastases remains a significant problem. Here, we identify the IL-11
receptor alpha subunit (IL-11Ralpha) as a cell surface marker of tumor
progression that correlates with poor prognosis in patients with osteosarcoma. We
also show that both IL-11Ralpha and its ligand, IL-11, are specifically up
regulated in human metastatic osteosarcoma cell lines; engagement of this
autocrine loop leads to tumor cell proliferation, invasion, and anchorage
independent growth in vitro. Consistently, IL-11Ralpha promotes lung colonization
by human metastatic osteosarcoma cells in vivo in an orthotopic mouse model.
Finally, we evaluate the IL-11Ralpha-targeted proapoptotic agent bone metastasis
targeting peptidomimetic (BMTP-11) in preclinical models of primary intratibial
osteosarcomas, observing marked inhibition of both tumor growth and lung
metastases. This effect was enhanced when BMTP-11 was combined with the
chemotherapeutic drug gemcitabine. Our combined data support the development of
approaches targeting IL-11Ralpha, and establish BMTP-11 as a leading drug
candidate for clinical translation in patients with high-risk osteosarcoma.
PMID- 28698376
TI - Frequency-specific directed interactions in the human brain network for language.
AB - The brain's remarkable capacity for language requires bidirectional interactions
between functionally specialized brain regions. We used magnetoencephalography to
investigate interregional interactions in the brain network for language while
102 participants were reading sentences. Using Granger causality analysis, we
identified inferior frontal cortex and anterior temporal regions to receive
widespread input and middle temporal regions to send widespread output. This fits
well with the notion that these regions play a central role in language
processing. Characterization of the functional topology of this network, using
data-driven matrix factorization, which allowed for partitioning into a set of
subnetworks, revealed directed connections at distinct frequencies of
interaction. Connections originating from temporal regions peaked at alpha
frequency, whereas connections originating from frontal and parietal regions
peaked at beta frequency. These findings indicate that the information flow
between language-relevant brain areas, which is required for linguistic
processing, may depend on the contributions of distinct brain rhythms.
PMID- 28698377
TI - Monomeric and fibrillar alpha-synuclein exert opposite effects on the catalytic
cycle that promotes the proliferation of Abeta42 aggregates.
AB - The coaggregation of the amyloid-beta peptide (Abeta) and alpha-synuclein is
commonly observed in a range of neurodegenerative disorders, including
Alzheimer's and Parkinson's diseases. The complex interplay between Abeta and
alpha-synuclein has led to seemingly contradictory results on whether alpha
synuclein promotes or inhibits Abeta aggregation. Here, we show how these
conflicts can be rationalized and resolved by demonstrating that different
structural forms of alpha-synuclein exert different effects on Abeta aggregation.
Our results demonstrate that whereas monomeric alpha-synuclein blocks the
autocatalytic proliferation of Abeta42 (the 42-residue form of Abeta) fibrils,
fibrillar alpha-synuclein catalyses the heterogeneous nucleation of Abeta42
aggregates. It is thus the specific balance between the concentrations of
monomeric and fibrillar alpha-synuclein that determines the outcome of the
Abeta42 aggregation reaction.
PMID- 28698378
TI - Haploid selection within a single ejaculate increases offspring fitness.
AB - An inescapable consequence of sex in eukaryotes is the evolution of a biphasic
life cycle with alternating diploid and haploid phases. The occurrence of
selection during the haploid phase can have far-reaching consequences for
fundamental evolutionary processes including the rate of adaptation, the extent
of inbreeding depression, and the load of deleterious mutations, as well as for
applied research into fertilization technology. Although haploid selection is
well established in plants, current dogma assumes that in animals, intact fertile
sperm within a single ejaculate are equivalent at siring viable offspring. Using
the zebrafish Danio rerio, we show that selection on phenotypic variation among
intact fertile sperm within an ejaculate affects offspring fitness. Longer-lived
sperm sired embryos with increased survival and a reduced number of apoptotic
cells, and adult male offspring exhibited higher fitness. The effect on embryo
viability was carried over into the second generation without further selection
and was equally strong in both sexes. Sperm pools selected by motile phenotypes
differed genetically at numerous sites throughout the genome. Our findings
clearly link within-ejaculate variation in sperm phenotype to offspring fitness
and sperm genotype in a vertebrate and have major implications for adaptive
evolution.
PMID- 28698379
TI - Entanglement and thermodynamics after a quantum quench in integrable systems.
AB - Entanglement and entropy are key concepts standing at the foundations of quantum
and statistical mechanics. Recently, the study of quantum quenches revealed that
these concepts are intricately intertwined. Although the unitary time evolution
ensuing from a pure state maintains the system at zero entropy, local properties
at long times are captured by a statistical ensemble with nonzero thermodynamic
entropy, which is the entanglement accumulated during the dynamics. Therefore,
understanding the entanglement evolution unveils how thermodynamics emerges in
isolated systems. Alas, an exact computation of the entanglement dynamics was
available so far only for noninteracting systems, whereas it was deemed
unfeasible for interacting ones. Here, we show that the standard quasiparticle
picture of the entanglement evolution, complemented with integrability-based
knowledge of the steady state and its excitations, leads to a complete
understanding of the entanglement dynamics in the space-time scaling limit. We
thoroughly check our result for the paradigmatic Heisenberg chain.
PMID- 28698380
TI - MmpL3 is the flippase for mycolic acids in mycobacteria.
AB - The defining feature of the mycobacterial outer membrane (OM) is the presence of
mycolic acids (MAs), which, in part, render the bilayer extremely hydrophobic and
impermeable to external insults, including many antibiotics. Although the
biosynthetic pathway of MAs is well studied, the mechanism(s) by which these
lipids are transported across the cell envelope is(are) much less known.
Mycobacterial membrane protein Large 3 (MmpL3), an essential inner membrane (IM)
protein, is implicated in MA transport, but its exact function has not been
elucidated. It is believed to be the cellular target of several antimycobacterial
compounds; however, evidence for direct inhibition of MmpL3 activity is also
lacking. Here, we establish that MmpL3 is the MA flippase at the IM of
mycobacteria and is the molecular target of BM212, a 1,5-diarylpyrrole compound.
We develop assays that selectively access mycolates on the surface of
Mycobacterium smegmatis spheroplasts, allowing us to monitor flipping of MAs
across the IM. Using these assays, we establish the mechanism of action of BM212
as a potent MmpL3 inhibitor, and use it as a molecular probe to demonstrate the
requirement for functional MmpL3 in the transport of MAs across the IM. Finally,
we show that BM212 binds MmpL3 directly and inhibits its activity. Our work
provides fundamental insights into OM biogenesis and MA transport in
mycobacteria. Furthermore, our assays serve as an important platform for
accelerating the validation of small molecules that target MmpL3, and their
development as future antituberculosis drugs.
PMID- 28698381
TI - Reasons for computerised provider order entry (CPOE)-based inpatient medication
ordering errors: an observational study of voided orders.
AB - OBJECTIVE: Medication voiding is a computerised provider order entry (CPOE)-based
discontinuation mechanism that allows clinicians to identify erroneous medication
orders. We investigated the accuracy of voiding as an indicator of clinician
identification and interception of a medication ordering error, and investigated
reasons and root contributors for medication ordering errors. METHOD: Using
voided orders identified with a void alert, we conducted interviews with ordering
and voiding clinicians, followed by patient chart reviews. A structured coding
framework was used to qualitatively analyse the reasons for medication ordering
errors. We also compared clinician-CPOE-selected (at time of voiding), clinician
reported (interview) and chart review-based reasons for voiding. RESULTS: We
conducted follow-up interviews on 101 voided orders. The positive predictive
value (PPV) of voided orders that were medication ordering errors was 93.1% (95%
CI 88.1% to 98.1%, n=94). Using chart review-based reasons as the gold standard,
we found that clinician-CPOE-selected reasons were less reflective (PPV=70.2%,
95% CI 61.0% to 79.4%) than clinician-reported (interview) (PPV=86.1%, 95%CI
78.2% to 94.1%) reasons for medication ordering errors. Duplicate (n=44) and
improperly composed (n=41) ordering errors were common, often caused by
predefined order sets and data entry issues. A striking finding was the use of
intentional violations as a mechanism to notify and seek ordering assistance from
pharmacy service. Nearly half of the medication ordering errors were voided by
pharmacists. DISCUSSION: We demonstrated that voided orders effectively captured
medication ordering errors. The mismatch between clinician-CPOE-selected and the
chart review-based reasons for error emphasises the need for developing
standardised operational descriptions for medication ordering errors. Such
standardisation can help in accurately identifying, tracking, managing and
sharing erroneous orders and their root contributors between healthcare
institutions, and with patient safety organisations.
PMID- 28698382
TI - Phosphatidylserine dictates the assembly and dynamics of caveolae in the plasma
membrane.
AB - Caveolae are bulb-shaped nanodomains of the plasma membrane that are enriched in
cholesterol and sphingolipids. They have many physiological functions, including
endocytic transport, mechanosensing, and regulation of membrane and lipid
transport. Caveola formation relies on integral membrane proteins termed
caveolins (Cavs) and the cavin family of peripheral proteins. Both protein
families bind anionic phospholipids, but the precise roles of these lipids are
unknown. Here, we studied the effects of phosphatidylserine (PtdSer),
phosphatidylinositol 4-phosphate (PtdIns4P), and phosphatidylinositol 4,5
bisphosphate (PtdIns(4,5)P2) on caveolar formation and dynamics. Using live-cell,
single-particle tracking of GFP-labeled Cav1 and ultrastructural analyses, we
compared the effect of PtdSer disruption or phosphoinositide depletion with
caveola disassembly caused by cavin1 loss. We found that PtdSer plays a crucial
role in both caveola formation and stability. Sequestration or depletion of
PtdSer decreased the number of detectable Cav1-GFP puncta and the number of
caveolae visualized by electron microscopy. Under PtdSer-limiting conditions, the
co-localization of Cav1 and cavin1 was diminished, and cavin1 degradation was
increased. Using rapamycin-recruitable phosphatases, we also found that the acute
depletion of PtdIns4P and PtdIns(4,5)P2 has minimal impact on caveola assembly
but results in decreased lateral confinement. Finally, we show in a model of
phospholipid scrambling, a feature of apoptotic cells, that caveola stability is
acutely affected by the scrambling. We conclude that the predominant plasmalemmal
anionic lipid PtdSer is essential for proper Cav clustering, caveola formation,
and caveola dynamics and that membrane scrambling can perturb caveolar stability.
PMID- 28698383
TI - Pancreatic beta-cell protection from inflammatory stress by the endoplasmic
reticulum proteins thrombospondin 1 and mesencephalic astrocyte-derived
neutrotrophic factor (MANF).
AB - Cytokine-induced endoplasmic reticulum (ER) stress is one of the molecular
mechanisms underlying pancreatic beta-cell demise in type 1 diabetes.
Thrombospondin 1 (THBS1) was recently shown to promote beta-cell survival during
lipotoxic stress. Here we show that ER-localized THBS1 is cytoprotective to rat,
mouse, and human beta-cells exposed to cytokines or thapsigargin-induced ER
stress. THBS1 confers cytoprotection by maintaining expression of mesencephalic
astrocyte-derived neutrotrophic factor (MANF) in beta-cells and thereby prevents
the BH3-only protein BIM (BCL2-interacting mediator of cell death)-dependent
triggering of the mitochondrial pathway of apoptosis. Prolonged exposure of beta
cells to cytokines or thapsigargin leads to THBS1 and MANF degradation and loss
of this prosurvival mechanism. Approaches that sustain intracellular THBS1 and
MANF expression in beta-cells should be explored as a cytoprotective strategy in
type 1 diabetes.
PMID- 28698384
TI - Palmitic acid dysregulates the Hippo-YAP pathway and inhibits angiogenesis by
inducing mitochondrial damage and activating the cytosolic DNA sensor cGAS-STING
IRF3 signaling mechanism.
AB - Impaired angiogenesis and wound healing carry significant morbidity and mortality
in diabetic patients. Metabolic stress from hyperglycemia and elevated free fatty
acids have been shown to inhibit endothelial angiogenesis. However, the
underlying mechanisms remain poorly understood. In this study, we show that
dysregulation of the Hippo-Yes-associated protein (YAP) pathway, an important
signaling mechanism in regulating tissue repair and regeneration, underlies
palmitic acid (PA)-induced inhibition of endothelial angiogenesis. PA inhibited
endothelial cell proliferation, migration, and tube formation, which were
associated with increased expression of mammalian Ste20-like kinases 1 (MST1),
YAP phosphorylation/inactivation, and nuclear exclusion. Overexpression of YAP or
knockdown of MST1 prevented PA-induced inhibition of angiogenesis. When searching
upstream signaling mechanisms, we found that PA dysregulated the Hippo-YAP
pathway by inducing mitochondrial damage. PA treatment induced mitochondrial DNA
(mtDNA) release to cytosol, and activated cytosolic DNA sensor cGAS-STING-IRF3
signaling. Activated IRF3 bound to the MST1 gene promoter and induced MST1
expression, leading to MST1 up-regulation, YAP inactivation, and angiogenesis
inhibition. Thus, mitochondrial damage and cytosolic DNA sensor cGAS-STING-IRF3
signaling are critically involved in PA-induced Hippo-YAP dysregulation and
angiogenesis suppression. This mechanism may have implication in impairment of
angiogenesis and wound healing in diabetes.
PMID- 28698385
TI - Retinoic acid receptor-related orphan receptor alpha stimulates adipose tissue
inflammation by modulating endoplasmic reticulum stress.
AB - Adipose tissue inflammation has been linked to metabolic diseases such as obesity
and type 2 diabetes. However, the molecules that mediate inflammation in adipose
tissue have not been addressed. Although retinoic acid receptor-related orphan
receptor alpha (RORalpha) is known to be involved in the regulation of
inflammatory response in some tissues, its role is largely unknown in adipose
tissue. Conversely, it is known that endoplasmic reticulum (ER) stress and
unfolding protein response (UPR) signaling affect the inflammatory response in
obese adipose tissue, but whether RORalpha regulates these processes remains
unknown. In this study, we investigate the link between RORalpha and adipose
tissue inflammation. We showed that the inflammatory response in macrophages or
3T3-L1 adipocytes stimulated by lipopolysaccharide, as well as adipose tissue in
obese mice, markedly increased the expression of RORalpha. Adenovirus-mediated
overexpression of RORalpha or treatment with the RORalpha-specific agonist SR1078
enhanced the expression of inflammatory cytokines and increased the number of
infiltrated macrophages into adipose tissue. Furthermore, SR1078 up-regulated the
mRNA expression of ER stress response genes and enhanced phosphorylations of two
of the three mediators of major UPR signaling pathways, PERK and IRE1alpha.
Finally, we found that alleviation of ER stress using a chemical chaperone
followed by the suppression of RORalpha induced inflammation in adipose tissue.
Our data suggest that RORalpha-induced ER stress response potentially contributes
to the adipose tissue inflammation that can be mitigated by treatment with
chemical chaperones. The relationships established here between RORalpha
expression, inflammation, and UPR signaling may have implications for therapeutic
targeting of obesity-related metabolic diseases.
PMID- 28698386
TI - Antagonistic Serotonergic and Octopaminergic Neural Circuits Mediate Food
Dependent Locomotory Behavior in Caenorhabditis elegans.
AB - Biogenic amines are conserved signaling molecules that link food cues to behavior
and metabolism in a wide variety of organisms. In the nematode Caenorhabditis
elegans, the biogenic amines serotonin (5-HT) and octopamine regulate a number of
food-related behaviors. Using a novel method for long-term quantitative
behavioral imaging, we show that 5-HT and octopamine jointly influence locomotor
activity and quiescence in feeding and fasting hermaphrodites, and we define the
neural circuits through which this modulation occurs. We show that 5-HT produced
by the ADF neurons acts via the SER-5 receptor in muscles and neurons to suppress
quiescent behavior and promote roaming in fasting worms, whereas 5-HT produced by
the NSM neurons acts on the MOD-1 receptor in AIY neurons to promote low
amplitude locomotor behavior characteristic of well fed animals. Octopamine,
produced by the RIC neurons, acts via SER-3 and SER-6 receptors in SIA neurons to
promote roaming behaviors characteristic of fasting animals. We find that 5-HT
signaling is required for animals to assume food-appropriate behavior, whereas
octopamine signaling is required for animals to assume fasting-appropriate
behavior. The requirement for both neurotransmitters in both the feeding and
fasting states enables increased behavioral adaptability. Our results define the
molecular and neural pathways through which parallel biogenic amine signaling
tunes behavior appropriately to nutrient conditions.SIGNIFICANCE STATEMENT
Animals adjust behavior in response to environmental changes, such as
fluctuations in food abundance, to maximize survival and reproduction. Biogenic
amines, such as like serotonin, are conserved neurotransmitters that regulate
behavior and metabolism in relation to energy status. Disruptions of biogenic
amine signaling contribute to human neurological diseases of mood, appetite, and
movement. In this study, we investigated the roles of the biogenic amines
serotonin and octopamine in regulating locomotion behaviors associated with
feeding and fasting in the roundworm Caenorhabditis elegans We identified neural
circuits through which these signals work to govern behavior. Understanding the
molecular pathways through which biogenic amines function in model organisms may
improve our understanding of dysfunctions of appetite and behavior found in
mammals, including humans.
PMID- 28698387
TI - Cortical and Subcortical Coordination of Visual Spatial Attention Revealed by
Simultaneous EEG-fMRI Recording.
AB - Visual spatial attention has been studied in humans with both
electroencephalography (EEG) and functional magnetic resonance imaging (fMRI)
individually. However, due to the intrinsic limitations of each of these methods
used alone, our understanding of the systems-level mechanisms underlying
attentional control remains limited. Here, we examined trial-to-trial
covariations of concurrently recorded EEG and fMRI in a cued visual spatial
attention task in humans, which allowed delineation of both the generators and
modulators of the cue-triggered event-related oscillatory brain activity
underlying attentional control function. The fMRI activity in visual cortical
regions contralateral to the cued direction of attention covaried positively with
occipital gamma-band EEG, consistent with activation of cortical regions
representing attended locations in space. In contrast, fMRI activity in
ipsilateral visual cortical regions covaried inversely with occipital alpha-band
oscillations, consistent with attention-related suppression of the irrelevant
hemispace. Moreover, the pulvinar nucleus of the thalamus covaried with both of
these spatially specific, attention-related, oscillatory EEG modulations. Because
the pulvinar's neuroanatomical geometry makes it unlikely to be a direct
generator of the scalp-recorded EEG, these covariational patterns appear to
reflect the pulvinar's role as a regulatory control structure, sending spatially
specific signals to modulate visual cortex excitability proactively. Together,
these combined EEG/fMRI results illuminate the dynamically interacting cortical
and subcortical processes underlying spatial attention, providing important
insight not realizable using either method alone.SIGNIFICANCE STATEMENT
Noninvasive recordings of changes in the brain's blood flow using functional
magnetic resonance imaging and electrical activity using electroencephalography
in humans have individually shown that shifting attention to a location in space
produces spatially specific changes in visual cortex activity in anticipation of
a stimulus. The mechanisms controlling these attention-related modulations of
sensory cortex, however, are poorly understood. Here, we recorded these two
complementary measures of brain activity simultaneously and examined their trial
to-trial covariations to gain insight into these attentional control mechanisms.
This multi-methodological approach revealed the attention-related coordination of
visual cortex modulation by the subcortical pulvinar nucleus of the thalamus
while also disentangling the mechanisms underlying the attentional enhancement of
relevant stimulus input and those underlying the concurrent suppression of
irrelevant input.
PMID- 28698388
TI - Delayed Cryptochrome Degradation Asymmetrically Alters the Daily Rhythm in
Suprachiasmatic Clock Neuron Excitability.
AB - Suprachiasmatic nuclei (SCN) neurons contain an intracellular molecular circadian
clock and the Cryptochromes (CRY1/2), key transcriptional repressors of this
molecular apparatus, are subject to post-translational modification through
ubiquitination and targeting for proteosomal degradation by the ubiquitin E3
ligase complex. Loss-of-function point mutations in a component of this ligase
complex, Fbxl3, delay CRY1/2 degradation, reduce circadian rhythm strength, and
lengthen the circadian period by ~2.5 h. The molecular clock drives circadian
changes in the membrane properties of SCN neurons, but it is unclear how
alterations in CRY1/2 stability affect SCN neurophysiology. Here we use male and
female Afterhours mice which carry the circadian period lengthening loss-of
function Fbxl3Afh mutation and perform patch-clamp recordings from SCN brain
slices across the projected day/night cycle. We find that the daily rhythm in
membrane excitability in the ventral SCN (vSCN) was enhanced in amplitude and
delayed in timing in Fbxl3Afh/Afh mice. At night, vSCN cells from Fbxl3Afh/Afh
mice were more hyperpolarized, receiving more GABAergic input than their Fbxl3+/+
counterparts. Unexpectedly, the progression to daytime hyperexcited states was
slowed by Afh mutation, whereas the decline to hypoexcited states was
accelerated. In long-term bioluminescence recordings, GABAA receptor blockade
desynchronized the Fbxl3+/+ but not the Fbxl3Afh/Afh vSCN neuronal network.
Further, a neurochemical mimic of the light input pathway evoked larger shifts in
molecular clock rhythms in Fbxl3Afh/Afh compared with Fbxl3+/+ SCN slices. These
results reveal unanticipated consequences of delaying CRY degradation, indicating
that the Afh mutation prolongs nighttime hyperpolarized states of vSCN cells
through increased GABAergic synaptic transmission.SIGNIFICANCE STATEMENT The
intracellular molecular clock drives changes in SCN neuronal excitability, but it
is unclear how mutations affecting post-translational modification of molecular
clock proteins influence the temporal expression of SCN neuronal state or
intercellular communication within the SCN network. Here we show for the first
time, that a mutation that prolongs the stability of key components of the
intracellular clock, the cryptochrome proteins, unexpectedly increases in the
expression of hypoexcited neuronal state in the ventral SCN at night and enhances
hyperpolarization of ventral SCN neurons at this time. This is accompanied by
increased GABAergic signaling and by enhanced responsiveness to a neurochemical
mimic of the light input pathway to the SCN. Therefore, post-translational
modification shapes SCN neuronal state and network properties.
PMID- 28698389
TI - The Best Thing I Saw at ASCO.
PMID- 28698390
TI - Randomized Controlled Trial of a Home-Based Walking Program to Reduce Moderate to
Severe Aromatase Inhibitor-Associated Arthralgia in Breast Cancer Survivors.
AB - BACKGROUND: In postmenopausal women diagnosed with breast cancer (BC), most BC
tumors are hormone receptor positive and guidelines recommend adjuvant endocrine
therapy that includes an aromatase inhibitor (AI). This study investigates the
impact of a 6-week, home-based, self-directed walking program on the commonly
reported side effect of AI-associated arthralgia (AIAA). MATERIALS AND METHODS:
In this phase II trial, consented BC patients were randomized to walking
Intervention (n = 31) or Wait List Control (WLC; n = 31). Eligibility criteria
included: stage 0-III BC, on AI for at least 4 weeks, >=3 on a 5-point scale
inquiring about joint symptom intensity "at its worst," and exercising <=150
minutes per week. Outcomes were self-reported joint symptoms and psychosocial
measures. Analyses comparing Intervention and WLC groups were conducted on an
intention-to-treat basis to assess intervention impact at 6 weeks
(postintervention) and at 6-months follow-up. Adjusted means were calculated to
assess differences in two groups. RESULTS: In our final sample (n = 62), mean age
was 64 years, 74% were white, and 63% had a body mass index of 30 or higher. At
postintervention, Intervention group participants reported significantly
increased walking minutes per week, reduced stiffness, less difficulty with
activities of daily living (ADL), and less perceived helplessness in managing
joint symptoms. At 6-months follow-up (postwalking period in both Intervention
and WLC), walking minutes per week had decreased significantly; however,
improvements in stiffness and difficulty with ADLs were maintained. CONCLUSION:
This study adds to the growing evidence base suggesting exercise as a safe
alternative or adjunct to medications for the management of AIAA. IMPLICATIONS
FOR PRACTICE: Breast cancer survivors whose adjuvant endocrine treatment includes
an aromatase inhibitor (AI) often experience the side effect of AI-associated
arthralgia (AIAA). This study investigates the impact of a 6-week, home-based,
self-directed walking program in the management of AIAA. Compared with Wait List
Control, women in the Intervention group reported significantly increased walking
minutes per week, reduced stiffness, less difficulty with activities of daily
living, and less perceived helplessness in managing joint symptoms. This study
adds to the growing evidence base suggesting exercise as a safe alternative or
adjunct to medications for the management of AIAA.
PMID- 28698392
TI - News Feature: Special agents offer modeling upgrade.
PMID- 28698411
TI - Estimation of turgor pressure through comparison between single plant cell and
pressurized shell mechanics.
AB - While plant growth is well known to rely on turgor pressure, it is challenging to
quantify the contribution of turgor pressure to plant cell rheology. Here we used
a custom-made micro-rheometer to quantify the viscoelastic behavior of isolated
plant cells while varying their internal turgor pressure. To get insight into how
plant cells adapt their internal pressure to the osmolarity of their medium, we
compared the mechanical behavior of single plant cells to that of a simple,
passive, pressurized shell: a soccer ball. While both systems exhibited the same
qualitative behavior, a simple mechanical model allowed us to quantify turgor
pressure regulation at the single cell scale.
PMID- 28698412
TI - [Cardiac Rehabilitation in Minimally Invasive Cardiac Surgery Coronary Artery
Bypass Grafting].
AB - OBJECTIVES: A purpose is to compare the in-hospital rehabilitation progress after
minimally invasive cardiac surgery coronary artery bypass grafting (MICS CABG)
with that after off pump coronary artery bypass grafting( OPCAB). METHODS: We
analyzed 60 patients who underwent coronary artery bypass grafting surgery from
January 2015 to December 2016. Fourteen patients underwent MICS CABG (MICS CABG
group) and 46 patients underwent OPCAB (OPCAB group). The post-operative days to
start standing position and independent walking, and hospitalization duration
were analyzed between the 2 groups. RESULTS: There were no significant
differences between the groups:standing position(1.2 vs 1.2 days) and independent
walking(4.8 vs 4.9 days). Hospitalization duration was shorter in MICS CABG
group(14.3 vs 17.5 days). CONCLUSION: MICS CABG may shorten hospitalization
length compared with OPCAB, however, further research will be needed.
PMID- 28698413
TI - [Aortic Stenosis Combined with Cold Agglutinin Disease].
AB - Cardiac surgery on a patient with cold agglutinin disease is high risk for
thromboembolism due to hypothermia perioperative. A 75-year-old woman with cold
agglutinin disease underwent aortic valve replacement for severe aortic stenosis.
Cold antibody was detected by preoperative screening test for blood transfusion.
In order to prevent thromboembolic event during the operation, we maintained
rectal temperature at around 36 degrees centigrade during the cardiopulmonary
bypass by warming blood in the bypass circuit. Furthermore, antegrade warm blood
cardioplegia was injected intermittently for keeping cardiac arrest. There was no
thromboembolic event perioperatively.
PMID- 28698414
TI - [Tricuspid Valve Replacement without Removing Transvenous Pacemaker Lead].
AB - Transvenous pacemaker lead occasionally impairs tricuspid valve coaptation
because of the direct injury like a perforation, the direct interference with the
valve, or the adhesion between the pacemaker leads and the valve leaflets,
resulting in severe tricuspid regurgitation. In these situation, tricuspid valve
replacement (TVR) is selected after the exchange from transvenous lead to
epicardial lead. However this procedure has some problems such as poor threshold
of the endcardial lead, the injury and the difficulty in transvenous lead
removal. We performed successful TVR without removing transvenous pacemaker lead
after the fixation to the annulus of posterior leaflet in tricuspid valve. This
technique is useful in a patient with tricuspid regurgitation due to the
influence of the pacemaker lead.
PMID- 28698415
TI - [Surgical Repair for Blunt Cardiac Rupture].
AB - Blunt cardiac injury is a life-threatening condition. We report 3 successful
cases in which we performed surgery for blunt cardiac injury. Three individuals
were injured, 2 in traffic accidents and the other being caught between a crane
and a steel frame. Echocardiograms and computed tomography scans revealed pooling
of bloody pericardial fluid in all 3 patients, who underwent emergency surgery.
Two patients needed sutures to control persistent bleeding. Although a heart-lung
machine was prepared at the start of surgery in all 3 cases, we did not need to
use it for any patient. Thus, prior to performing such surgery, it is necessary
to ascertain its need.
PMID- 28698416
TI - [Second Pneumothorax in an Ehlers-Danlos Syndrome Patient Initially Treated by
Bullaectomy Twenty-two Years Ago].
AB - A 2nd pneumothorax developed in a 40-years-old man after his 1st bilateral
pneumothoraces were successfully treated by bullaectomies 22 years ago. For the
past 10 years, he has suffered major complications such as repeated bleeding into
the digestive tract due to vascular-type Ehlers-Danlos syndrome (vEDS). Although
preoperative computed tomography demonstrated multiple bullae at the apex of the
right lung, any abnormal findings suggesting tissue fragility was not found. At
surgery, visceral pleura of the right lung had an almost normal appearance
through a thoracoscope. However, we found that gentle touch with soft surgical
equipment resulted in serious pleural damage leading to new air leakage. Our case
suggests a progressive fragility of the lung in a vEDS patient, and a less
invasive pleural covering technique would therefore be preferable when major
complications become evident, despite previous successful bullaectomy.
PMID- 28698417
TI - [Intravenous Ablation for Lower Extremity Varices to Prevent Recurrent Pulmonary
Embolism in Klippel-Trenaunay Syndrome;Report of a Case].
AB - Klippel-Trenaunay syndrome( KTS) is a complex congenital anomaly characterized by
lower extremity varix and venous malformations, port-wine stains, and soft tissue
and bone hypertrophy. We present a case of a 35-year-old man of KTS with
pulmonary embolism (PE). The patient was referred to our hospital complaining of
the leg pain and sudden onset of dyspnea. Enhanced computed tomography (CT)
showed lower extremity varices, superficial thrombophlebitis and bilateral
pulmonary thrombi. No venous malformations except for varicose veins were
revealed in the limbs or pelvis. The patient received adequate anticoagulant
therapy with edoxaban, followed by intravenous radiofrequency ablation for lower
extremity varices. Two months after the operation, the patient suffered from
thrombophlebitis in the leg again, however, CT showed no pulmonary thrombus. This
case report suggests that intravenous ablation for lower extremity varices in KTS
prevented recurrent PE.
PMID- 28698418
TI - [Reconstruction of Anterior Mitral Leaflet Using Fresh Autologous Pericardial
Patch for Active Infective Endocarditis;Report of a Case].
AB - Several reports have described that the prognosis of patients with mitral valve
regurgitation due to active infective endocarditis (IE) is better after mitral
valve plasty (MVP) than replacement (MVR). However, extensive destruction of
valve tissue might cause difficulties with MVP. We repaired a widely-affected
anterior mitral leaflet (AML) using an autologous pericardial patch. A 44-year
old woman with mitral regurgitation presented with prolonged fever and backache.
We made a diagnosis of active IE accompanied by mitral valve regurgitation. We
performed MVP, widely resected the infected areas of the AML, and reconstructed
the defective area using the pericardial patch. She was discharged after four
weeks of antibiotic therapy, when she was free of recurrence. The pericardial
patch facilitated MVP and was effective for treating mitral valve regurgitation
due to active IE.
PMID- 28698419
TI - [Aortoesophageal Fistula due to Aortic Aneurysm;Report of a Case].
AB - A 77-year-old woman presented with general fatigue, was found to have anemia, and
was referred to our hospital. Upper gastrointestinal endoscopy revealed a
submucosal elevated lesion with a bleeding site and debris at the middle thoracic
esophagus. Enhanced computed tomography demonstrated a thoracic aortic aneurysm
compressing the esophagus. She was diagnosed with an aorto-esophageal fistula due
to the thoracic aortic aneurysm. Graft replacement was performed under partial
extracorporeal circulation. Because the perforation of the esophagus was small,
omental flap transposition was performed without esophagectomy. Her post
operative course was uneventful, and she has been doing well without any
infective episodes over 3 years after surgery.
PMID- 28698420
TI - [Intravascular Hemolysis Caused by Stenosis of an Elephant Trunk;Report of a
Case].
AB - Symptomatic intravascular hemolysis after prosthetic aortic graft replacement is
rare. It is primarily attributed to mechanical injury of red blood cells caused
by stenosis of the vascular graft. A 50-year-old man presented with hemolytic
anemia, 5 years after total arch replacement with an elephant trunk for type A
aortic dissection. The hemolysis was caused by graft stenosis of the elephant
trunk. Endovascular treatment for the stenotic elephant trunk was successfully
performed. The postoperative course was uneventful, and the hemolysis was
resolved immediately after operation.
PMID- 28698421
TI - [Tricuspid Valve Repair in a Patient with Isolated Tricuspid Valve Infective
Endocarditis with Pulmonary Embolism;Report of a Case].
AB - We report a case of 39-year-old man who developed tricuspid valve infective
endocarditis with a complication of pulmonary embolism. He was transferred to our
institution because of intermittent fever and enlargement of the vegetation of
the tricuspid valve in spite of optimal antibiotics treatment. Computed
tomography revealed pulmonary embolism, and transesophageal echocardiography
showed a large and mobile vegetation (22*10 mm) on the tricuspid valve with
moderate regurgitation. In addition, Streptococcus agalactiae was identified in
blood cultures. The patient underwent surgical resection of the vegetation
followed by tricuspid valve repair including De Vega's annuloplasty. Antibiotic
therapy was continued for 4 weeks after surgery, and he was discharged on the
31st postoperative day. No endocarditis nor tricuspid valve dysfunction has re
occurred.
PMID- 28698422
TI - [Atrial Septal Hematoma after Repair of Ventricular Septal Defect;Report of a
Case].
AB - A 3-month-old female with ventricular septal defect underwent definitive repair.
In the operation, a venting tube was inserted through the incised patent foramen
ovale. The ventricular septal defect was closed using a patch and the incised
patent foramen ovale was directly closed. A transesophageal echography showed no
abnormal findings in the operating room. On 1st postoperative day, the patient's
heart rate and pressure of the superior vena cava increased while blood pressure
decreased. A transthoracic echocardiography revealed an atrial septal hematoma.
After conservative therapy, the heart rate and pressure of the superior vena cava
gradually decreased while blood pressure increased. The atrial septal hematoma
disappeared spontaneously. The patient was discharged on 16th postoperative day.
The atrial septal hematoma appears to have a good prognosis, but sometimes can be
poor resulting and death. Meticulous and constant observation is required to
detect an atrial septal hematoma.
PMID- 28698423
TI - [Early Structural Valve Deterioration of Trifecta Biological Prosthesis;Report of
a Case].
AB - Trifecta valve is a 3rd-generation, stented bioprosthesis which is made from one
bovine pericardial sheet. A 77-years-old male patient had undergone combine
aortic valve replacement (AVR) using a 23-mm Trifecta valve and ascending aorta
replacement for severe aortic valve regurgitation and ascending aorta aneurysm.
The postoperative period was uneventful. However, he presented with dyspnea on
effort and severe aortic valve regurgitation 31 months after operation. Re-do AVR
with a new bioprosthetic valve was performed via 2nd sternotomy. Surgical
inspection revealed that the Trifecta valve had a parastent tear in the left
coronary cusp without any calcification or vegetation. We report our experience
with a case of early structural valve deterioration of Trifecta biological
prosthesis and review relevant literatures.
PMID- 28698424
TI - [Aortic Valve Replacement Via a Partial Sternotomy in an Ankylosing Skeletal
Hyperostosis Patient after Prophylactic Tracheostomy;Report of a Case].
AB - A 77-year-old man presented with exertional dyspnea. The patient had a history of
ankylosing skeletal hyperostosis and sleep apnea syndrome. Echocardiographic
examination revealed severe aortic valve regurgitation. The patient underwent a
prophylactic tracheostomy 2 weeks before cardiac surgery to decrease his risk of
perioperative respiratory failure. He successfully underwent aortic valve
replacement through a lower partial sternotomy. His postoperative course was
uneventful, and the tracheostoma was closed 6 months after the cardiac surgery.
PMID- 28698425
TI - [Marked Aneurysmal Expansion Caused by Type II Endoleaks Eight Years after
Thoracic Endovascular Aortic Repair;Report of a Case].
AB - We report a case of marked aneurysmal expansion by type II endoleaks 8 years
after thoracic endovascular aortic repair. The preoperative chest computed
tomography (CT) demonstrated the descending thoracic aorta of 95 mm with type II
endoleak. We performed suture closure of 3 endoleaks and partial aneurysmorrhaphy
via left thoracotomy under partial cardiopulmonary bypass. The postoperative CT
showed no endoleak with shrinkage of the aneurysm. The patient was discharged on
the 21th postoperative day uneventfully.
PMID- 28698426
TI - [Seminoma of the Mediastinum with Cystic Change;Report of a Case].
AB - The patient was a 25-year-old man. He was diagnosed as having a mediastinal tumor
based on chest radiography. Chest computed tomography and magnetic resonance
imaging revealed a cystic tumor in the anterior mediastinum. Total resection of
the tumor with median sternotomy was performed. We anticipated that the tumor was
a thymic cyst or teratoma, but pathological findings indicated a seminoma. The
patient was discharged without any complication, and no recurrence of the lesion
has been observed for 8 years after surgery without adjuvant therapy.
PMID- 28698427
TI - [Metastatic Atypical Meningioma of the Lung;Report of a Case].
AB - A 56-years-old woman, who had undergone a complete resection for atypical
meningioma (grade 2 of World Health Organization classification)8 years before
was admitted to our hospital to treat a mass on the right middle lobe detected by
chest X-ray. The mass was resected successfully by video-assisted thoracoscopic
surgery and pathological diagnosis of the tumor was a metastatic atypical
meningioma. We experienced a rare case of extracranial pulmonary metastasis of
meningioma. Grade 2 meningioma is thought to have malignant potential of local
recurrence and extracranial metastasis compared to grade 1 meningioma, so long
term observation may be necessary after resection of atypical meningioma.
PMID- 28698428
TI - [Thoracoscopic Pericardial Fenestration for Refractory Pericardial Effusion with
Cardiac Tamponade;Report of a Case].
AB - We performed thoracoscopic pericardial fenestration for a 70-year-old man who
suffered from refractory pericardial effusion with cardiac tamponade. Under
general anesthesia with differential lung ventilation, pericardial fenestration
followed by needle aspiration of the enough pericardial effusion to obtain the
working space was carried out by thoracoscopic surgery through the left thoracic
space. Postoperative course was uneventful and reaccumulation of the pericardial
fluid has not been observed more than 2 years after surgery.
PMID- 28698429
TI - [Thymoma with Multilocular Cystic Change;Report of a Case].
AB - A 21-year-old male was pointed out an abnormal shadow on chest X-ray. Chest
computed tomography showed a multilocular cystic mass of 10*4*4 cm in size in the
anterior mediastinum. The tumor and the left lobe of the thymus was resected by
median sternotomy. Pathologically, type AB thymoma as found in the wall of the
cyst.
PMID- 28698430
TI - [Extralobar Sequestration Difficult to Establish Preoperative Diagnosis;Report of
a Case].
AB - Pulmonary sequestration is a rare congenital pulmonary anomaly. Here we report a
case of extralobar sequestration with calcification. A 34-year-old man was
admitted to our department because of a tumor shadow on the chest radiological
examination. Computed tomography examination revealed a mass measuring 5 cm above
the left diaphragm. The mass contained cysts and calcification. Aberrant vessels
were not detected. Teratoma, hamartoma or solitary fibrous tumor were suspected
and the surgical treatment was performed. The postoperative pathological
diagnosis was extralobar pulmonary sequestration.
PMID- 28698431
TI - [Progress and Future of the Training Plan for Cancer Professionals - Looking Back
for 10 Years].
AB - In order to increase cancer professionals in Japan, the first phase of training
plan for cancer professionals was performed for 5 years from 2007t o 2011, and
the second one was performed for 5 years from 2012 to 2016. 95 universities for
18 hubs in the first phase and 100 universities for 15 hubs in the second one
participated in this project 2,590 graduate students in the first phase and 2,319
students for 3 years in the second phase learned. Although the number of cancer
professionals increased after the start of this project, it is still half of the
set points and more efforts are required for this project. From 2017, the new
training plan for cancer professionals will start for the third phase, and
various professionals such as genome medicine professionals, rare cancer
professionals, pediatric cancer professionals and those for the life-stage
problems in cancer patients will be educated.
PMID- 28698432
TI - [Treatment Strategy for Soft Tissue Sarcomas].
AB - Surgical excision is the most reliable treatment for the localized soft tissue
sarcoma, and chemotherapy and/or radiation therapy may be recommended as adjuvant
therapy, depending on the histologic type, grading, tumor size and location. For
the unresectable tumors, radiation therapy including particle beam radiation
therapy may be taken into consideration. For the recurrent or metastatic disease,
the combination therapy with chemotherapy, radiation therapy and surgical
excision may be indicated to improve the patient's prognosis and QOL.
PMID- 28698433
TI - [Molecular Target Therapy for Soft Tissue Sarcoma].
AB - Soft tissue sarcoma(STS)is one of the rare and intractable cancers, and most
types of STS are not sensitive to chemotherapy. Development of specific molecular
target therapy for each type of STS is necessary. There are specific chromosome
translocations in 20-30% of STS, but their products are mostly transcriptional
factors, and target therapy for those factors are difficult to develop.
Trabectedin is an alkylating agent and is also inhibit function of
transcriptional factors, and shows efficacy for translocation-related
sarcoma(TRS)such as myxoid liposarcoma. As molecular target therapies for gene
mutations, success in molecular target therapy for c-kit and PDGFR mutation in
GIST was followed by efficacy for rare sarcomas such as IMT or DFSP, but there
are few developments in other sarcomas. STSs are frequently associated with
angiogenesis and angiogenesis inhibitors such as pazopanib show some efficacy.
Then immune checkpoint inhibitors also have been developed.
PMID- 28698434
TI - [The Role of Novel Agents in the Treatment of Soft Tissue Sarcoma].
AB - Soft tissue sarcomas are rare disease and the development of efficacious drug is
urgently needed. The challenge is continuing, and recently 2 drugs, trabectedin
and eribulin, were approved in Japan. Both drugs were investigated in patients
with liposarcoma or leiomyosarcoma in randomized phase III trials as compared to
dacarbazine. Eribulin was superior in terms of overall survival and trabectedin
was superior in terms of progression-free survival compared to dacarbazine. This
article reviews the efficacy and safety of both drugs.
PMID- 28698435
TI - [Histology-Specific Chemotherapy in Soft-Tissue Sarcomas].
AB - Soft-tissue sarcomas(STSs)are rare mesenchymal tumors, accounting for less than
1%of all adult malignancies. STSs also have diversity, with more than 50
different histological subtypes. While surgical complete resection is a
definitive treatment for localized STS, chemotherapy is the treatment option for
managing locally advanced and metastatic STS. Although doxorubicin +/-ifosfamide
is still the first-line therapy for most STS subtypes, some STSs(alveolar soft
part sarcoma, clear cell sarcoma, epithelioid sarcoma and extraskeletal myxoid
chondrosarcoma)have been reported to have little response to these cytotoxic
chemotherapies. Additionally, the treatment options after the failure of first
line therapy were very limited. The recent emergence of new therapeutic options
in Japan allows us to treat patients with second-line therapy, including
pazopanib, trabectedin and eribulin. However the priority and potential role of
these drugs as second-line therapy are still controversial, and the outcomes with
these drugs are still unsatisfactory due to the low contribution of response and
survival rates. As increasing numbers of reproducible genetic alterations in STS
are identified, novel molecular development has been paid attention to identify
targets for the application of histology-driven therapy. We herein give an
overview of histology-specific chemotherapy for STSs in Japan, highlighting first
line chemotherapy regimens, including molecular-targeted drugs other than
doxorubicin- based ones, and introduce the efficacy of trabectedin and eribulin
as second-line chemotherapy with consideration of liposarcoma subtypes.
PMID- 28698436
TI - [Central Nervous System Tumor Metastatic Brain Tumor].
PMID- 28698437
TI - [I. Management of Brain Metastasis in Patients with Lung Cancer].
PMID- 28698438
TI - [II. Brain Metastasis of Breast Cancer].
PMID- 28698439
TI - [III. Stereotactic Irradiation for Metastatic Brain Tumor].
PMID- 28698440
TI - [IV. Psycho-Oncology in Patients with Metastatic Brain Tumor].
PMID- 28698441
TI - [Combination Therapy with Radiation, Temozolomide, and Bevacizumab after Partial
Tumor Removal in Glioblastoma Patients with Low Performance Status].
AB - INTRODUCTION: It is unclear whether or not bevacizumab(Bev)has a curative ability
in newly diagnosed glioblastoma(GBM) patients with low Karnofsky performance
status(KPS). MATERIALS AND METHODS: Four of 14 patients with newly diagnosed GBM
received combination therapy with extended local radiation, temozolomide(TMZ),
and Bev after partialremovalor biopsy of the tumor. RESULTS: The average patient
age was 77.2 years(range 67-85)and the male-to-female ratio was 1:3. In all
cases, magnetic resonance imaging showed that combination therapy decreased tumor
volume and peritumoral edema volume. The therapy was successfully administered to
3 patients without decreasing their KPS. However, 1 patient with seeding lesions
dropped out of therapy because of deteriorating consciousness and decreasing KPS.
DISCUSSION: Subgroup analysis in a randomized control study(AVAglio)showed that
patients with a PS score of 1-2(corresponding to a KPS score of 60-80)tended to
have prolonged survival after Bev treatment compared with those with a PS score
of 0(corresponding to a KPS score of 90-100). In the present study,
radiochemotherapy with Bev decreased lesion and edema volumes in all patients,
and led to maintained or improved KPS in 3 patients. These results suggest that
the treatment is potentially effective for patients with newly diagnosed GBM and
lower KPS.
PMID- 28698442
TI - Incidence of Ophthalmic Disorders in Patients Treated with the Antineoplastic
Agent S-1.
AB - S-1 is an oral antineoplastic agent containing tegafur, gimeracil, and oteracil
potassium. Recently, ophthalmic disorders, particularly epiphora, have been
reported. We retrospectively investigated the incidence of ophthalmic disorders
in patients treated with a regimen containing S-1 at our institution. Ophthalmic
disorders were noted in 28 of 261 patients(10.7%). These included epiphora(17
cases), eye discharge(10 cases), conjunctivitis(6cases ), blurred vision(3
cases), and eye discomfort(2 cases), as well as eye pain, pruritus, dry eye,
hordeolum, and visual loss(1 case each). The median time from starting treatment
to appearance of the condition was 3.0(interquartile range 1.5-4.5)months and the
median cumulative S-1 dose was 4.2(interquartile range 2.2-9.5)g. More men than
women developed ophthalmic disorders on S-1. The median total dose and duration
of treatment were higher in those developed ophthalmic disorders than in those
who did not (12.4 g vs 6.3g and 8.6 months vs 4.4 months). Epiphora was the most
common of a number of ophthalmic disorders seen in our patients treated with S-1.
Patients and physicians should be fully informed of the potential association
between S-1 and ophthalmic disorders, and patients receiving this treatment need
to be carefully monitored.
PMID- 28698443
TI - [Medical Assistance Based on Interviews Conducted before Physician Examination by
a Pharmacist for Outpatients with Thyroid Cancer Treated with Lenvatinib].
AB - In municipal hospitals, there are few cases of thyroid cancer for which the multi
kinase inhibitor lenvatinib is used. Moreover, there are very few reports of
lenvatinib use. We examined interventions related to the use of lenvatinib made
at the pharmaceutical outpatient clinic in our facility. Seven patients received
lenvatinib. The prescription proposals from the pharmacist( 45 cases)provided
advice on dosage(15.6%), discontinuation of medication(11.1%), supportive
care(64.4%), and other advice(9.0%). The prescription acceptance rate was 84.4%.
Among the prescription proposals of supportive care, there were suggestions
regarding blood pressure(26.7%), diarrhea(8.9%), nausea(8.9%), and oral
hemorrhage(6.7%). Some patients also experienced side effects, such as
abnormalities in equilibrioception and visual field defects; however, the
relationship between such abnormalities and lenvatinib is unclear. In addition,
we asked physicians to confirm if the outpatient pharmacists contributed to the
examination process. We believe that lenvatinib administration can be continued
safely with pharmaceutical outpatient clinic support for patients, even in
municipal hospitals.
PMID- 28698444
TI - [A Case of Central Diabetes Insipidus That Was Caused by Pituitary Metastasis of
Lung Adenocarcinoma and Was Controlled by Radiation Therapy].
AB - BACKGROUND: Pituitary metastasis of lung cancer is rare; however, it often causes
diabetes insipidus. Although the majority of such patients are treated with
radiation therapy, it remains unclear whether diabetes insipidus can be
controlled by radiation therapy. CASE: A 72-year-old man was admitted to our
hospital for hemosputum, headache, and polyuria. A chest CT scan showed a 3.0 cm
mass in the left upper lobe of his lung. Bronchofiberscopy results confirmed the
pathological diagnosis of lung adenocarcinoma. Based on the findings from PET-CT,
head MRI, and endocrine tests, the diagnosis of lung adenocarcinoma( cT1bN0M1b,
stage IV)accompanied with central diabetes insipidus caused by pituitary
metastasis was made. Oral administration of desmopressin reduced urine volumes;
however, chemotherapy for achieving stable disease in the primary tumor was
ineffective in controlling the symptoms of diabetes insipidus. Chemotherapy was
discontinued after 4 months because of severe hematological toxicity. During 2
months after the cessation of chemotherapy, polyuria worsened and, therefore,
radiation therapy for pituitary metastasis was started. Following the radiation
therapy, an apparent reduction in urine volume was observed. CONCLUSION: Our
experience of this case suggests that radiation therapy for pituitary metastasis
should be considered at the time when diabetes insipidus becomes clinically
overt.
PMID- 28698445
TI - [A Case of Albumin-Bound Paclitaxel-Induced Peripheral Neuropathy without
Exacerbation].
AB - Albumin-bound paclitaxel(nab-PTX)-associated neuropathy decreases the quality of
life of cancer patients and leads to dose modification, discontinuation of
chemotherapy, and occasionally dose-limiting toxicity. In the present case study,
a 92- year-old female patient with peritoneal cancer of carcinomatous peritonitis
and carcinomatous ascites was treated with carboplatin plus nab-PTX every 4 weeks
as first-line chemotherapy, and a good response was achieved following 4 cycles
of this regimen. However, the patient developed Grade 3 peripheral neuropathy and
stopped the therapy. As a result, the peripheral neuropathy gradually improved.
After 1 year, ascites appeared, and tumor marker(CA125)levels increased. We tried
an 8-h infusion of nab-PTX to avoid peripheralneuropathy. After 4 cycles, a
positive response was achieved without exacerbation of the peripheralneuropathy.
Administering nab-PTX over shorter periods of time has generally led to increased
peripheral neuropathy. The severity of peripheralneuropathy can be reduced with a
longer infusion time.
PMID- 28698446
TI - [A Case of Long-Term Survival of a Patient with Gastric Cancer with Synchronous
Liver Metastasis and Portal Vein Thrombus after Multidisciplinary Treatment].
AB - A 77-year-old man was diagnosed with gastric cancer with synchronous single liver
metastasis and portal vein thrombus. His HER2 immunohistochemistry tumor score
was 3+; therefore, we administered trastuzumab plus capecitabine plus cisplatin.
After 2 courses of chemotherapy, we observed disappearance of the portal vein
thrombus and tumor reduction as a partial response, according to the RECIST
guidelines. We performed distal gastrectomy and right lobectomy; the therapeutic
grades of the primary and metastatic tumors were 1a and 2, respectively. We
administered postoperative chemotherapy, and no recurrent lesions have appeared 2
years after surgery. Multidisciplinary treatment for gastric cancer with liver
metastasis might be a feasible and useful strategy.
PMID- 28698447
TI - [A Case of Perianal Squamous Cell Carcinoma with Left Inguinal Lymph Node
Metastasis That Showed a Complete Response More Than Five Years after
Chemotherapy and Concomitant Proton Beam Therapy].
AB - We report a case of perianal squamous cell carcinoma and left inguinal lymph node
metastasis that showed a complete response more than 5 years after chemotherapy
and concomitant proton beam therapy. A 34-year-old woman was referred to our
hospital for an anal tumor and a left inguinal tumor. A digital rectal
examination revealed a tumor in the anterior wall of the anal canal. In addition,
the left inguinal lymph nodes were swollen, leading us to suspect metastases.
Biopsy specimens confirmed poorly differentiated squamous cell carcinoma. We made
a diagnosis of squamous cell carcinoma T4bN2M0, Stage III b. The patient was
treated with chemotherapy consisting of 5-FU(700mg/m / 2/day; continuous
intravenous administra- tion)on days 1-5, and CDDP(70mg/m / 2/day)on day 1, along
with concomitant proton beam therapy. A total of 45 Gy of X-ray irradiation was
administered to the primary lesion, pelvis, and groin area. Furthermore, 24.2 Gy
of proton beam therapy was administered to the primary lesion, and 28.6 Gy to the
left inguinal lymph nodes. The patient tolerated this treatment with no severe
adverse effects. The tumor disappeared completely 1 month after this treatment,
and biopsy specimens confirmed the absence of any viable cancer cells. The
patient has been alive with no sign of recurrence for 5 years.
PMID- 28698448
TI - [A Case of Chronic Myelogenous Leukemia That Developed Fibrous Pericarditis Owing
to Nilotinib Use].
AB - A 64-year-old man was diagnosed with chronic-phase chronic myelogenous
leukemia(CML)in May 2009. He was treated with imatinib and achieved complete
cytogenetic response(CCyR)in 2 months. After 4 months of treatment, he developed
interstitial pneumonia and became intolerant to imatinib. He was then switched to
nilotinib from October of the same year. In June 2013, he was diagnosed with drug
induced pericarditis resulting from nilotinib use, and thus, nilotinib was
discontinued. Subsequently, he was followed up without specific treatment for
CML. In January 2014, he was admitted to the Dept. of Cardiovascular, Renal and
Metabolic Medicine at our hospital because of heart failure. After examinations
of cardiac function, he was diagnosed with constrictive pericarditis. Therefore,
pericardiolysis was performed by the Dept. of Cardiovascular Surgery at our
hospital. Pathologic findings showed hyaline-like fibrous tissue proliferation in
the pericardium, which was diagnosed as fibrous pericarditis induced by
nilotinib. We report a case of chronic myelogenous leukemia that developed
fibrous pericarditis owing to nilotinib use.
PMID- 28698449
TI - In Vitro Evaluation of the Inhibitory Activity of Thymoquinone in Combatting
Candida albicans in Denture Stomatitis Prevention.
AB - Candida albicans adhesion and proliferation on denture bases may lead to denture
stomatitis, which is a common and recurrent problem in denture wearers. The goal
of this study was to assess the inhibitory effect of thymoquinone incorporated in
the polymethyl methacrylate denture base material against Candida albicans.
Eighty acrylic resin specimens were fabricated and divided into eight groups (n =
10) according to thymoquinone concentrations of 0.5%, 1%, 1.5%, 2%, 2.5%, 3%, and
5% of acrylic powder. Two methods were used to evaluate the effect of
thymoquinone on Candida albicans: the slide count and the serial dilution test. A
multivariate analysis of variance (MANOVA) and the post-hoc Tukey's Honestly
Significant Difference (HSD) test were performed to compare the difference of
means between the observations taken at various intervals with baseline. The p
value was statistically significant at <=0.05. According to the slide count and
the serial dilution test, the mean number of adhered Candida albicans in the
control group was 5436.9 +/- 266 and 4691.4 +/- 176.8; however, this number
dramatically decreased to 0 +/- 0 and 32.4 +/- 1.7 in group 8 (concentration 5%).
These results suggest that the incorporation of thymoquinone into the acrylic
resin denture base material might be effective in preventing Candida albicans
adhesion.
PMID- 28698450
TI - Analytical Techniques and Pharmacokinetics of Gastrodia elata Blume and Its
Constituents.
AB - Gastrodia elata Blume (G. elata), commonly called Tianma in Chinese, is an
important and notable traditional Chinese medicine (TCM), which has been used in
China as an anticonvulsant, analgesic, sedative, anti-asthma, anti-immune drug
since ancient times. The aim of this review is to provide an overview of the
abundant efforts of scientists in developing analytical techniques and performing
pharmacokinetic studies of G. elata and its constituents, including sample
pretreatment methods, analytical techniques, absorption, distribution,
metabolism, excretion (ADME) and influence factors to its pharmacokinetics. Based
on the reported pharmacokinetic property data of G. elata and its constituents,
it is hoped that more studies will focus on the development of rapid and
sensitive analytical techniques, discovering new therapeutic uses and
understanding the specific in vivo mechanisms of action of G. elata and its
constituents from the pharmacokinetic viewpoint in the near future. The present
review discusses analytical techniques and pharmacokinetics of G. elata and its
constituents reported from 1985 onwards.
PMID- 28698451
TI - Phenolics from Mikania micrantha and Their Antioxidant Activity.
AB - A phytochemical study on the aerial parts of Mikania micrantha led to the
isolation of two new phenolic compounds, benzyl 5-O-beta-d-glucopyranosyl-2,5
dihydroxybenzoate (1) and (7S,8R)-threo-dihydroxydehydrodiconiferyl alcohol 9
acetate (2), together with twelve known compounds, benzyl 2-O-beta-d
glucopyranosyl-2,6-dihydroxybenzoate (3), 4-allyl-2,6-dimethoxyphenol glucoside
(4), (+)-isolariciresinol (5), icariol A2 (6), 9,10-dihydroxythymol (7), 8,9,10
trihydroxythymol (8), caffeic acid (9), p-coumaric acid (10), ethyl
protocatechuate (11), procatechuic aldehyde (12), 4-hydroxybenzoic acid (13), and
hydroquinone (14). Their structures were elucidated on the basis of extensive
spectroscopic analysis. Except 8 and 9, all the other compounds were isolated
from this plant species for the first time. The antioxidant activity of those
isolated compounds were evaluated using three different assays. Compounds 1, 2,
3, 9, 10, 13, and 14 demonstrated significant 2,2'-azinobis-(3
ethylbenzthiazoline-6-sulphonic acid) (ABTS) free radical cation scavenging
activity ranging from SC50 0.31 to 4.86 uM, which were more potent than l
ascorbic acid (SC50 = 10.48 uM). Compounds 5, 9, 11, and 12 exhibited more potent
1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity (SC50 = 16.24
21.67 uM) than l-ascorbic acid (39.48 uM). Moreover, the ferric reducing
antioxidant power (FRAP) of compounds 2, 5, 9, and 11 were discovered to be also
comparable to or even more potent than l-ascorbic acid.
PMID- 28698452
TI - Therapeutic Delivery of Butyrylcholinesterase by Brain-Wide Viral Gene Transfer
to Mice.
AB - Recent research shows that butyrylcholinesterase (BChE) is not simply a liver
enzyme that detoxifies bioactive esters in food and medications. In fact, in
pursuing other goals, we recently found that it has an equally important role in
regulating the peptide hormone ghrelin and its impact on hunger, obesity, and
emotions. Here, we present and examine means of manipulating brain BChE levels by
viral gene transfer, either regionally or globally, to modulate ghrelin signaling
for long-term therapeutic purposes and to set the stage for exploring the
neurophysiological impact of such an intervention.
PMID- 28698453
TI - Plasma Homocysteine and Serum Folate and Vitamin B12 Levels in Mild Cognitive
Impairment and Alzheimer's Disease: A Case-Control Study.
AB - Homocysteine (Hcy) is a risk factor for brain atrophy, cognitive impairment, and
dementia. Vitamin B12 and folate are cofactors necessary for the methylation of
Hcy. However, there is some debate regarding the differing levels of plasma Hcy
and serum folate and vitamin B12 among healthy controls, patients with mild
cognitive impairment (MCI), and patients with Alzheimer's disease (AD). This
study aimed to evaluate how the levels of plasma Hcy and its biological
determinants, folate and vitamin B12, are related to MCI and AD in older Chinese
adults. This is a case-control study including 112 subjects with MCI, 89 AD
patients and 115 healthy controls. Diagnosis of AD was made according to the
NINCDS-ADRDA and MCI with modified Petersen's criteria. Serum folate and vitamin
B12 concentrations were analyzed by radioimmunoassay, and plasma Hcy was assessed
by a high-performance liquid chromatography-fluorescence method. Multivariate
analysis of regression was used to examine the odds ratio (OR) of MCI or AD with
Hcy or vitamin levels. Results have shown that serum folate and vitamin B12
levels were significantly lower, but the plasma Hcy level was higher, in patients
with MCI and AD than in healthy controls. Multivariate regression analyses showed
that subjects in the lowest folate tertile had significantly higher adjusted ORs
for MCI (OR: 3.07; 95% confidence interval [CI]: 1.12, 8.07) and AD (3.42; 95%
CI: 1.15, 8.34) compared to subjects in the highest tertile. The highest Hcy
tertile was significantly associated with MCI (adjusted OR: 2.81; 95% CI: 1.15,
4.73) and AD (adjusted OR: 3.64; 95% CI: 1.13, 9.04) compared to the lowest
tertile. No association existed between low vitamin B12 levels and AD or MCI (p >
0.05). Low blood levels of folate and vitamin B12 and elevated Hcy levels were
associated with MCI and AD in older Chinese adults, and the association was
stronger for AD.
PMID- 28698454
TI - Metal-Mediated Addition of N-Nucleophiles to Isocyanides: Mechanistic Aspects.
AB - Despite the long history of the investigation of nucleophilic addition to metal
bound isocyanides, some important aspects of the reaction mechanism remain
unclear even for the simplest systems. In this work, the addition of the sp3-N,
sp2-N, and mixed sp2/sp3-N nucleophiles (i.e., HNMe2, HN=CPh2, and H2N-N=CPh2,
respectively) to isocyanides C=NR coordinated to the platinum(II) centers in the
complexes cis-[Pt(C=NCy)(2-pyz)(dppe)]+ (2-pyz = 2-pyrazyl, dmpe =
Me2PCH2CH2PMe2) and cis-[PtCl2(C=NXyl)(C=NMe)] was studied in detail by
theoretical (DFT) methods. The mechanism of these reactions is stepwise
associative rather than concerted and it includes the addition of a nucleophile
to the isocyanide C atom, deprotonation of the nucleophilic moiety in the
resulting intermediate, and protonation of the isocyanide N atom to give the
final product. The calculated activation energy (DeltaG?) of all reactions is in
the range of 19.8-22.4 kcal/mol.
PMID- 28698455
TI - Development of Polioencephalomyelitis in Cesarean-Derived Colostrum-Deprived Pigs
Following Experimental Inoculation with Either Teschovirus A Serotype 2 or
Serotype 11.
AB - Teschovirus encephalomyelitis is a sporadic disease associated with Teschovirus A
(PTV) serotype 1 and, less frequently, other serotypes. In recent years, the
number of cases submitted to the Iowa State University Veterinary Diagnostic
Laboratory with a history of posterior paresis has increased. Submission
histories from various regions of the United States suggest a trend for clinical
disease to persist in herds and affect a wider age-range of pigs than
historically reported. Polioencephalitis and/or myelitis was consistently present
and PTV was detected in affected neural tissue by PCR in a portion of cases.
Sequencing from two clinical cases identified PTV-2 and PTV-11. To assess
neuropathogenicity of these isolates, 5-week-old cesarean derived and colostrum
deprived pigs were assigned to three groups: negative control (n = 4), PTV-2
inoculated (n = 7), and PTV-11-inoculated (n = 7). Three PTV-2-inoculated pigs
developed mild incoordination of the hind limbs, one of which progressed to
posterior ataxia. While all PTV-11-inoculated pigs showed severe neurological
signs consistent with Teschovirus encephalomyelitis, no evidences of neurological
signs were observed in sham-inoculated animals. All PTV-2- and PTV-11-inoculated
pigs had microscopic lesions consistent with Teschovirus encephalomyelitis. To
our knowledge, this is the first description of PTV-11 and experimental study
demonstrating the neuropathogenicity of PTV-11 in the United States.
PMID- 28698456
TI - Combining NMR Spectroscopy and Chemometrics to Monitor Structural Features of
Crude Hep-arin.
AB - Because of the complexity and global nature of the heparin supply chain, the
control of heparin quality during manufacturing steps is essential to ensure the
safety of the final active pharmaceutical ingredient (API). For this reason,
there is a need to develop consistent analytical methods able to assess the
quality of heparin early in production (i.e., as the crude heparin before it is
purified to API under cGMP conditions). Although a number of analytical
techniques have been applied to characterize heparin APIs, few of them have been
applied for crude heparin structure and composition analyses. Here, to address
this issue, NMR spectroscopy and chemometrics were applied to characterize 88
crude heparin samples. The samples were also analyzed by strong anion exchange
HPLC (SAX-HPLC) as an orthogonal check of the purity levels of the crudes
analyzed by NMR. The HPLC data showed that the chemometric analysis of the NMR
data differentiated the samples based on their purity. These orthogonal
approaches differentiated samples according their glycosaminoglycan (GAG)
composition and their mono and disaccharide composition and structure for each
GAG family (e.g., heparin/heparan, dermatan sulfate, and chondroitin sulfate A).
Moreover, quantitative HSQC and multivariate analysis (PCA) were used to
distinguish between crude heparin of different animal and tissue sources.
PMID- 28698457
TI - Review of Ligand Specificity Factors for CYP1A Subfamily Enzymes from Molecular
Modeling Studies Reported to-Date.
AB - The cytochrome P450 (CYP) family 1A enzymes, CYP1A1 and CYP1A2, are two of the
most important enzymes implicated in the metabolism of endogenous and exogenous
compounds through oxidation. These enzymes are also known to metabolize
environmental procarcinogens into carcinogenic species, leading to the advent of
several types of cancer. The development of selective inhibitors for these P450
enzymes, mitigating procarcinogenic oxidative effects, has been the focus of many
studies in recent years. CYP1A1 is mainly found in extrahepatic tissues while
CYP1A2 is the major CYP enzyme in human liver. Many molecules have been found to
be metabolized by both of these enzymes, with varying rates and/or positions of
oxidation. A complete understanding of the factors that govern the specificity
and potency for the two CYP 1A enzymes is critical to the development of
effective inhibitors. Computational molecular modeling tools have been used by
several research groups to decipher the specificity and potency factors of the
CYP1A1 and CYP1A2 substrates. In this review, we perform a thorough analysis of
the computational studies that are ligand-based and protein-ligand complex-based
to catalog the various factors that govern the specificity/potency toward these
two enzymes.
PMID- 28698458
TI - Integrin alphavbeta3 Signaling in Tumor-Induced Bone Disease.
AB - Tumor-induced bone disease is common among patients with advanced solid cancers,
especially those with breast, prostate, and lung malignancies. The tendency of
these cancers to metastasize to bone and induce bone destruction is, in part, due
to alterations in integrin expression and signaling. Substantial evidence from
preclinical studies shows that increased expression of integrin alphavbeta3 in
tumor cells promotes the metastatic and bone-invasive phenotype. Integrin
alphavbeta3 mediates cell adhesion to several extracellular matrix proteins in
the bone microenvironment which is necessary for tumor cell colonization as well
as the transmission of mechanical signals for tumor progression. This review will
discuss the alphavbeta3 integrin receptor in the context of tumor-induced bone
disease. Specifically, the focus will be the role of alphavbeta3 in modulating
cancer metastasis to bone and tumor cell response to the bone microenvironment,
including downstream signaling pathways that contribute to tumor-induced
osteolysis. A better understanding of integrin dysregulation in cancer is
critical to developing new therapeutics for the prevention and treatment of bone
metastases.
PMID- 28698460
TI - Adults and Children in Low-Income Households that Participate in Cost-Offset
Community Supported Agriculture Have High Fruit and Vegetable Consumption.
AB - This paper examines fruit and vegetable intake (FVI) in low-income households
that participated in a cost-offset (CO), or 50% subsidized, community-supported
agriculture (CSA) program. CSA customers paid farms upfront for a share of the
harvest, and received produce weekly throughout the growing season. A cohort of
adults and children 2-12 y in a summer CO-CSA were surveyed online twice: August
2015 (n = 41) and February 2016 (n = 23). FVI was measured by the National Cancer
Institute's (NCI) Fruit and Vegetable Screener (FVS) and an inventory of locally
grown fruits and vegetables. FVI relative to United States (US) recommendations
and averages, and across seasons, were tested with non-parametric tests and
paired t-tests (p < 0.05). Both adults and children in the CO-CSA had higher FVI
than the US averages, and more often met recommendations for vegetables. Some
summer fruits and vegetables were more often eaten when locally in-season. The CO
CSA model warrants further examination as an avenue for improving vegetable
consumption among adults and children in low-income households. However,
causality between CO-CSA participation and FVI cannot be inferred, as CO-CSA
participants may be positive deviants with respect to FVI. A multi-state
randomized controlled trial is currently underway to evaluate impacts of CO-CSAs
on FVI and related outcomes.
PMID- 28698459
TI - Dietary Natural Products for Prevention and Treatment of Breast Cancer.
AB - Breast cancer is the most common cancer among females worldwide. Several
epidemiological studies suggested the inverse correlation between the intake of
vegetables and fruits and the incidence of breast cancer. Substantial
experimental studies indicated that many dietary natural products could affect
the development and progression of breast cancer, such as soy, pomegranate,
mangosteen, citrus fruits, apple, grape, mango, cruciferous vegetables, ginger,
garlic, black cumin, edible macro-fungi, and cereals. Their anti-breast cancer
effects involve various mechanisms of action, such as downregulating ER-alpha
expression and activity, inhibiting proliferation, migration, metastasis and
angiogenesis of breast tumor cells, inducing apoptosis and cell cycle arrest, and
sensitizing breast tumor cells to radiotherapy and chemotherapy. This review
summarizes the potential role of dietary natural products and their major
bioactive components in prevention and treatment of breast cancer, and special
attention was paid to the mechanisms of action.
PMID- 28698461
TI - Dereplication-Guided Isolation of New Phenylpropanoid-Substituted Diglycosides
from Cistanche salsa and Their Inhibitory Activity on NO Production in
Macrophage.
AB - Dereplication allows for a rapid identification of known and unknown compounds in
plant extracts. In this study, we performed liquid chromatography-mass
spectroscopy (LC-MS)- based dereplication using data from ESI+ QTOF-MS for the
analysis of phenylpropanoid-substituted diglycosides, the major active
constituents of Cistanche salsa (C. A. Mey.) Beck. Using TOF-MS alone, the
substructures of these compounds could be unambiguously confirmed based on the
characteristic fragmentation patterns of various product ions. HPLC-MS based
profiling of C. salsa also allowed for the detection of new phenylpropanoid
substituted diglycosides from this plant. Of them, five new phenylpropanoid
substituted diglycosides, named cistansalsides A-E (5, 6, 12, 17 and 18), were
isolated. Their structures were elucidated through spectroscopic methods
including NMR and MS analysis. All the isolates were tested for their inhibitory
activity against NO production in RAW 264.7 cells stimulated by LPS. Of the
tested compounds, compounds 5, 11, 13 and 18 showed moderate inhibitory activity
on inducible NO synthase. Compounds 11, 13 and 18 also inhibited the
phosphorylation of NF-kappaB in macrophages. None of the compounds displayed
significant cytotoxicity.
PMID- 28698462
TI - Using Health Impact Assessment as an Interdisciplinary Teaching Tool.
AB - Health Impact Assessment (HIA) courses are teaching public health and urban
planning students how to assess the likely health effects of proposed policies,
plans, and projects. We suggest that public health and urban planning have
complimentary frameworks for training practitioners to address the living
conditions that affect health. Planning perspectives emphasize practical skills
for impacting community change, while public health stresses professional purpose
and ethics. Frameworks from both disciplines can enhance the HIA learning
experience by helping students tackle questions related to community impact,
engagement, social justice, and ethics. We also propose that HIA community
engagement processes can be enriched through an empathetic practice that focuses
on greater personal introspection.
PMID- 28698463
TI - Peptide Nucleic Acids as miRNA Target Protectors for the Treatment of Cystic
Fibrosis.
AB - Cystic Fibrosis (CF) is one of the most common life shortening conditions in
Caucasians. CF is caused by mutations in the CF Transmembrane Conductance
Regulator (CFTR) gene which result in reduced or altered CFTR functionality.
Several microRNAs (miRNAs) downregulate the expression of CFTR, thus causing or
exacerbating the symptoms of CF. In this context, the design of anti-miRNA agents
represents a valid functional tool, but its translation to the clinic might lead
to unpredictable side effects because of the interference with the expression of
other genes regulated by the same miRNAs. Herein, for the first time, is proposed
the use of peptide nucleic acids (PNAs) to protect specific sequences in the
3'UTR (untranslated region) of the CFTR messenger RNA (mRNA) by action of miRNAs.
Two PNAs (7 and 13 bases long) carrying the tetrapeptide Gly-SerP-SerP-Gly at
their C-end, fully complementary to the 3'UTR sequence recognized by miR-509-3p,
have been synthesized and the structural features of target PNA/RNA
heteroduplexes have been investigated by spectroscopic and molecular dynamics
studies. The co-transfection of the pLuc-CFTR-3'UTR vector with different
combinations of PNAs, miR-509-3p, and controls in A549 cells demonstrated the
ability of the longer PNA to rescue the luciferase activity by up to 70% of the
control, thus supporting the use of suitable PNAs to counteract the reduction in
the CFTR expression.
PMID- 28698464
TI - Leaf Area Index Estimation Using Chinese GF-1 Wide Field View Data in an
Agriculture Region.
AB - Leaf area index (LAI) is an important vegetation parameter that characterizes
leaf density and canopy structure, and plays an important role in global change
study, land surface process simulation and agriculture monitoring. The wide field
view (WFV) sensor on board the Chinese GF-1 satellite can acquire multi-spectral
data with decametric spatial resolution, high temporal resolution and wide
coverage, which are valuable data sources for dynamic monitoring of LAI.
Therefore, an automatic LAI estimation algorithm for GF-1 WFV data was developed
based on the radiative transfer model and LAI estimation accuracy of the
developed algorithm was assessed in an agriculture region with maize as the
dominated crop type. The radiative transfer model was firstly used to simulate
the physical relationship between canopy reflectance and LAI under different soil
and vegetation conditions, and then the training sample dataset was formed. Then,
neural networks (NNs) were used to develop the LAI estimation algorithm using the
training sample dataset. Green, red and near-infrared band reflectances of GF-1
WFV data were used as the input variables of the NNs, as well as the
corresponding LAI was the output variable. The validation results using field LAI
measurements in the agriculture region indicated that the LAI estimation
algorithm could achieve satisfactory results (such as R2 = 0.818, RMSE = 0.50).
In addition, the developed LAI estimation algorithm had potential to
operationally generate LAI datasets using GF-1 WFV land surface reflectance data,
which could provide high spatial and temporal resolution LAI data for
agriculture, ecosystem and environmental management researches.
PMID- 28698465
TI - Progestin Intrauterine Devices and Metformin: Endometrial Hyperplasia and Early
Stage Endometrial Cancer Medical Management.
AB - Globally, endometrial cancer is the sixth leading cause of female cancer-related
deaths. Non-atypical endometrial hyperplasia (EH), has a lifetime progression
rate to endometrial cancer ranging from less than 5%, if simple without atypia,
to 40%, if complex with atypia. Site specific, long-acting intrauterine devices
(IUDs) provide fertility sparing, progestin-based EH medical management. It is
unclear which IUD is most beneficial, or if progesterone sensitizing metformin
offers improved outcomes. For resolution, PubMed searches for "Mirena" or
"Metformin," "treatment," "endometrial hyperplasia," or "stage 1 endometrial
cancer," were performed, yielding 33 articles. Of these, 19 articles were
included. The 60 mg high-dose frameless IUD/20 mcg levonorgestrel has achieved
sustained regression of Grade 3 endometrial intraepithelial neoplasia for 14
years. Case series on early stage endometrial cancer (EC) treatment with IUDs
have 75% or greater regression rates. For simple through complex EH with atypia,
the 52 mg-IUD/10-20 mcg-LNG-14t has achieved 100% complete regression in 6
months. Clearly, IUDs have an outcome advantage over oral progestins. However,
studies on metformin for EH, and of progestins or metformin for early stage EC
management are underpowered, with inadequate dose ranges to achieve significant
differences in, or optimal outcomes for, the treatment modalities. Therefore,
outcomes from the feMMe trial for the 52 mg-IUD/10-20 mcg-LNG-14t and metformin
will fill a gap in the literature.
PMID- 28698466
TI - Multi-National Banknote Classification Based on Visible-light Line Sensor and
Convolutional Neural Network.
AB - Automatic recognition of banknotes is applied in payment facilities, such as
automated teller machines (ATMs) and banknote counters. Besides the popular
approaches that focus on studying the methods applied to various individual types
of currencies, there have been studies conducted on simultaneous classification
of banknotes from multiple countries. However, their methods were conducted with
limited numbers of banknote images, national currencies, and denominations. To
address this issue, we propose a multi-national banknote classification method
based on visible-light banknote images captured by a one-dimensional line sensor
and classified by a convolutional neural network (CNN) considering the size
information of each denomination. Experiments conducted on the combined banknote
image database of six countries with 62 denominations gave a classification
accuracy of 100%, and results show that our proposed algorithm outperforms
previous methods.
PMID- 28698467
TI - Effect of Soy Isoflavones on Growth of Representative Bacterial Species from the
Human Gut.
AB - The present work aimed to assess the susceptibility of dominant and
representative bacterial populations from the human gut to isoflavones and their
metabolites. To do so, the minimum inhibitory concentration (MIC) of isoflavone
glycosides, isoflavone aglycones, and equol to 37 bacterial strains was
determined by broth microdilution. Additionally, for 10 representative strains,
growth curves, growth rate (MU), and optical density (OD600 nm) of the cultures
at 24 h were also determined. MICs of daidzin, genistin, daidzein, and genistein
were >2048 MUg mL-1 for all strains assayed, while that of equol ranged from 16
MUg mL-1 for Bifidobacterium animalis subsp. animalis to >2048 MUg mL-1 for
Enterobacteriaceae strains. Changes in growth curves, MU, and final OD were
observed among the species in the presence of all tested compounds. Genistein
reduced MU of Bacteroides fragilis, Lactococcus lactis subsp. lactis, and Slackia
equolifaciens, while both genistein and equol increased that of Lactobacillus
rhamnosus and Faecalibacterium prausnitzii. Compared to controls, lower final OD
in the presence of aglycones and equol were recorded for some strains but were
higher for others. Altogether, the results suggest that isoflavone-derived
compounds could modify numbers of key bacterial species in the gut, which might
be associated with their beneficial properties.
PMID- 28698468
TI - Adoption of Clean Cookstoves after Improved Solid Fuel Stove Programme Exposure:
A Cross-Sectional Study in Three Peruvian Andean Regions.
AB - This study examined measures of clean cookstove adoption after improved solid
fuel stove programmes in three geographically and culturally diverse rural Andean
settings and explored factors associated with these measures. A questionnaire was
administered to 1200 households on stove use and cooking behaviours including
previously defined factors associated with clean cookstove adoption. Logistic
multivariable regressions with 16 pre-specified explanatory variables were
performed for three outcomes; (1) daily improved solid fuel stove use, (2) use of
liquefied petroleum gas stove and (3) traditional stove displacement. Eighty
seven percent of households reported daily improved solid fuel stove use, 51%
liquefied petroleum gas stove use and 66% no longer used the traditional
cookstove. Variables associated with one or more of the three outcomes are:
education, age and civil status of the reporting female, household wealth and
size, region, encounters of problems with the improved solid fuel stove,
knowledge of somebody able to build an improved solid fuel stove, whether stove
parts are obtainable in the community, and subsidy schemes. We conclude that to
be successful, improved solid fuel stove programmes need to consider (1) existing
household characteristics, (2) the household's need for ready access to
maintenance and repair, and (3) improved knowledge at the community level.
PMID- 28698469
TI - Potential of Integrin Inhibitors for Treating Ovarian Cancer: A Literature
Review.
AB - Epithelial ovarian cancer is a fatal disease, with a cure rate of only 30%.
Several recent studies have targeted integrins for cancer treatment. Preclinical
studies have shown the effectiveness of several integrin inhibitors for blocking
cancer progression, especially by blocking angiogenesis. Because the initial
critical step in ovarian cancer metastasis is the attachment of cancer cells to
the peritoneum or omentum and because clinical trials have provided positive
results for anti-angiogenic therapy, therapies targeting integrins may be the
most feasible approach for treating cancer. This review summarizes the current
understanding of integrin biology in ovarian cancer metastasis and various
therapeutic approaches involving integrin inhibitors. However, no integrin
inhibitor has shown favorable results thus far. However, conjugates of cytotoxic
agents with the triplet sequence arginine-glycine-aspartate (RGD) peptides
targeting alpha5beta1-, alphavbeta3-, and alphavbeta6-integrins may be promising
integrin-targeting therapies for further clinical investigation.
PMID- 28698470
TI - Real-Time Amperometric Recording of Extracellular H2O2 in the Brain of
Immunocompromised Mice: An In Vitro, Ex Vivo and In Vivo Characterisation Study.
AB - We detail an extensive characterisation study on a previously described dual
amperometric H2O2 biosensor consisting of H2O2 detection (blank) and degradation
(catalase) electrodes. In vitro investigations demonstrated excellent H2O2
sensitivity and selectivity against the interferent, ascorbic acid. Ex vivo
studies were performed to mimic physiological conditions prior to in vivo
deployment. Exposure to brain tissue homogenate identified reliable sensitivity
and selectivity recordings up to seven days for both blank and catalase
electrodes. Furthermore, there was no compromise in pre- and post-implanted
catalase electrode sensitivity in ex vivo mouse brain. In vivo investigations
performed in anaesthetised mice confirmed the ability of the H2O2 biosensor to
detect increases in amperometric current following locally perfused/infused H2O2
and antioxidant inhibitors mercaptosuccinic acid and sodium azide. Subsequent
recordings in freely moving mice identified negligible effects of control saline
and sodium ascorbate interference injections on amperometric H2O2 current.
Furthermore, the stability of the amperometric current was confirmed over a five
day period and analysis of 24-h signal recordings identified the absence of
diurnal variations in amperometric current. Collectively, these findings confirm
the biosensor current responds in vivo to increasing exogenous and endogenous
H2O2 and tentatively supports measurement of H2O2 dynamics in freely moving NOD
SCID mice.
PMID- 28698471
TI - Two Coiled-Coil Proteins, WEB1 and PMI2, Suppress the Signaling Pathway of
Chloroplast Accumulation Response that Is Mediated by Two Phototropin-Interacting
Proteins, RPT2 and NCH1, in Seed Plants.
AB - Chloroplast movement is induced by blue light in a broad range of plant species.
Weak light induces the chloroplast accumulation response and strong light induces
the chloroplast avoidance response. Both responses are essential for efficient
photosynthesis and are mediated by phototropin blue-light receptors. J-DOMAIN
PROTEIN REQUIRED FOR CHLOROPLAST ACCUMULATION RESPONSE 1 (JAC1) and two coiled
coil domain proteins WEAK CHLOROPLAST MOVEMENT UNDER BLUE LIGHT 1 (WEB1) and
PLASTID MOVEMENT IMPAIRED 2 (PMI2) are required for phototropin-mediated
chloroplast movement. Genetic analysis suggests that JAC1 is essential for the
accumulation response and WEB1/PMI2 inhibit the accumulation response through the
suppression of JAC1 activity under the strong light. We recently identified two
phototropin-interacting proteins, ROOT PHOTOTROPISM 2 (RPT2) and NPH3/RPT2-like
(NRL) PROTEIN FOR CHLOROPLAST MOVEMENT 1 (NCH1) as the signaling components
involved in chloroplast accumulation response. However, the relationship between
RPT2/NCH1, JAC1 and WEB1/PMI2 remained to be determined. Here, we performed
genetic analysis between RPT2/NCH1, JAC1, and WEB1/PMI2 to elucidate the signal
transduction pathway.
PMID- 28698472
TI - Oxidative Stress Associated with Chilling Injury in Immature Fruit: Postharvest
Technological and Biotechnological Solutions.
AB - Immature, vegetable-like fruits are produced by crops of great economic
importance, including cucumbers, zucchini, eggplants and bell peppers, among
others. Because of their high respiration rates, associated with high rates of
dehydration and metabolism, and their susceptibility to chilling injury (CI),
vegetable fruits are highly perishable commodities, requiring particular storage
conditions to avoid postharvest losses. This review focuses on the oxidative
stress that affects the postharvest quality of vegetable fruits under chilling
storage. We define the physiological and biochemical factors that are associated
with the oxidative stress and the development of CI symptoms in these
commodities, and discuss the different physical, chemical and biotechnological
approaches that have been proposed to reduce oxidative stress while enhancing the
chilling tolerance of vegetable fruits.
PMID- 28698473
TI - The Chemokine Receptor CXCR6 Evokes Reverse Signaling via the Transmembrane
Chemokine CXCL16.
AB - Reverse signaling is a signaling mechanism where transmembrane or membrane-bound
ligands transduce signals and exert biological effects upon binding of their
specific receptors, enabling a bidirectional signaling between ligand and
receptor-expressing cells. In this study, we address the question of whether the
transmembrane chemokine (C-X-C motif) ligand 16, CXCL16 is able to transduce
reverse signaling and investigate the biological consequences. For this, we used
human glioblastoma cell lines and a melanoma cell line as in vitro models to show
that stimulation with recombinant C-X-C chemokine receptor 6 (CXCR6) or CXCR6
containing membrane preparations induces intracellular (reverse) signaling.
Specificity was verified by RNAi experiments and by transfection with expression
vectors for the intact CXCL16 and an intracellularly-truncated form of CXCL16. We
showed that reverse signaling via CXCL16 promotes migration in CXCL16-expressing
melanoma and glioblastoma cells, but does not affect proliferation or protection
from chemically-induced apoptosis. Additionally, fast migrating cells isolated
from freshly surgically-resected gliomas show a differential expression pattern
for CXCL16 in comparison to slowly-migrating cells, enabling a possible
functional role of the reverse signaling of the CXCL16/CXCR6 pair in human brain
tumor progression in vivo.
PMID- 28698474
TI - A Novel Spatial Feature for the Identification of Motor Tasks Using High-Density
Electromyography.
AB - Estimation of neuromuscular intention using electromyography (EMG) and pattern
recognition is still an open problem. One of the reasons is that the pattern
recognition approach is greatly influenced by temporal changes in electromyograms
caused by the variations in the conductivity of the skin and/or electrodes, or
physiological changes such as muscle fatigue. This paper proposes novel features
for task identification extracted from the high-density electromyographic signal
(HD-EMG) by applying the mean shift channel selection algorithm evaluated using a
simple and fast classifier-linear discriminant analysis. HD-EMG was recorded from
eight subjects during four upper-limb isometric motor tasks (flexion/extension,
supination/pronation of the forearm) at three different levels of effort. Task
and effort level identification showed very high classification rates in all
cases. This new feature performed remarkably well particularly in the
identification at very low effort levels. This could be a step towards the
natural control in everyday applications where a subject could use low levels of
effort to achieve motor tasks. Furthermore, it ensures reliable identification
even in the presence of myoelectric fatigue and showed robustness to temporal
changes in EMG, which could make it suitable in long-term applications.
PMID- 28698475
TI - Pedestrian Detection Based on Adaptive Selection of Visible Light or Far-Infrared
Light Camera Image by Fuzzy Inference System and Convolutional Neural Network
Based Verification.
AB - A number of studies have been conducted to enhance the pedestrian detection
accuracy of intelligent surveillance systems. However, detecting pedestrians
under outdoor conditions is a challenging problem due to the varying lighting,
shadows, and occlusions. In recent times, a growing number of studies have been
performed on visible light camera-based pedestrian detection systems using a
convolutional neural network (CNN) in order to make the pedestrian detection
process more resilient to such conditions. However, visible light cameras still
cannot detect pedestrians during nighttime, and are easily affected by shadows
and lighting. There are many studies on CNN-based pedestrian detection through
the use of far-infrared (FIR) light cameras (i.e., thermal cameras) to address
such difficulties. However, when the solar radiation increases and the background
temperature reaches the same level as the body temperature, it remains difficult
for the FIR light camera to detect pedestrians due to the insignificant
difference between the pedestrian and non-pedestrian features within the images.
Researchers have been trying to solve this issue by inputting both the visible
light and the FIR camera images into the CNN as the input. This, however, takes a
longer time to process, and makes the system structure more complex as the CNN
needs to process both camera images. This research adaptively selects a more
appropriate candidate between two pedestrian images from visible light and FIR
cameras based on a fuzzy inference system (FIS), and the selected candidate is
verified with a CNN. Three types of databases were tested, taking into account
various environmental factors using visible light and FIR cameras. The results
showed that the proposed method performs better than the previously reported
methods.
PMID- 28698476
TI - Acute Supplementation with High Dose Vitamin D3 Increases Serum Anti-Mullerian
Hormone in Young Women.
AB - Anti-Mullerian hormone (AMH) is a paracrine regulator of ovarian follicles.
Vitamin D (Vit D) regulates AMH production in vitro, but its role as a regulator
of ovarian AMH production is contentious. If Vit D influences ovarian AMH
production, then an acute rise in Vit D level should lead to an acute rise in
circulating AMH levels. This hypothesis was tested with a randomized double-blind
design, with 18-25-year-old women recruited from the community. The study was
conducted in early spring, when the marker of Vit D level (25-hydroxyvitamin D,
25(OH)D) tends to be at its nadir. The women consumed either an oral dose of
50,000 IU of Vit D3 (n = 27) or placebo (n = 22). The initial 25(OH)D +/- SD
value was 53.6 +/- 23.3 nmol/L, with 42 of the 49 women having a value below 75
nmol/L, consistent with seasonal nadir. All women receiving Vit D3 treatment
exhibited a robust increase in serum 25(OH)D within 1 day (15.8 +/- 1.1 nmol/L (n
= 27), p < 0.0001), with the increase sustained over the study week. Circulating
levels of AMH in the women receiving Vit D3 progressively rose during the
following week, with a mean increase of 12.9 +/- 3.7% (n = 24, p = 0.001). The
study supports the hypothesis that Vit D's positive effects on the fertility of
woman may involve the regulation of ovarian AMH levels.
PMID- 28698477
TI - On Transform Domain Communication Systems under Spectrum Sensing Mismatch: A
Deterministic Analysis.
AB - Towards the era of mobile Internet and the Internet of Things (IoT), numerous
sensors and devices are being introduced and interconnected. To support such an
amount of data traffic, traditional wireless communication technologies are
facing challenges both in terms of the increasing shortage of spectrum resources
and massive multiple access. The transform-domain communication system (TDCS) is
considered as an alternative multiple access system, where 5G and mobile IoT are
mainly focused. However, previous studies about TDCS are under the assumption
that the transceiver has the global spectrum information, without the
consideration of spectrum sensing mismatch (SSM). In this paper, we present the
deterministic analysis of TDCS systems under arbitrary given spectrum sensing
scenarios, especially the influence of the SSM pattern to the signal to noise
ratio (SNR) performance. Simulation results show that arbitrary SSM pattern can
lead to inferior bit error rate (BER) performance.
PMID- 28698478
TI - Antifungal and Ichthyotoxic Sesquiterpenoids from Santalum album Heartwood.
AB - In our continuing study on a survey of biologically active natural products from
heartwood of Santalum album (Southwest Indian origin), we newly found potent fish
toxic activity of an n-hexane soluble extract upon primary screening using
killifish (medaka) and characterized alpha-santalol and beta-santalol as the
active components. The toxicity (median tolerance limit (TLm) after 24 h at 1.9
ppm) of alpha-santalol was comparable with that of a positive control, inulavosin
(TLm after 24 h at 1.3 ppm). These fish toxic compounds including inulavosin were
also found to show a significant antifungal effect against a dermatophytic
fungus, Trichophyton rubrum. Based on a similarity of the morphological change of
the immobilized Trichophyton hyphae in scanning electron micrographs between
treatments with alpha-santalol and griseofulvin (used as the positive control),
inhibitory effect of alpha-santalol on mitosis (the antifungal mechanism proposed
for griseofulvin) was assessed using sea urchin embryos. As a result, alpha
santalol was revealed to be a potent antimitotic agent induced by interference
with microtubule assembly. These data suggested that alpha-santalol or sandalwood
oil would be promising to further practically investigate as therapeutic agent
for cancers as well as fungal skin infections.
PMID- 28698480
TI - Comparison of Dietary Intakes of 7-Year-Old Children Enrolled in Observational
Birth Cohort Studies on the Isle of Man and in South-west England.
AB - There is concern regarding the amount of fruit and vegetables consumed and high
sugar intakes in children's diets. Regional dietary differences in the British
Isles could underlie variations in health outcomes, but little is known about
these differences. Our aim was to compare diets of children enrolled in
observational birth cohort studies in the Isle of Man (IoM-ELSPAC) and in south
west England (ALSPAC). Dietary intakes were assessed by 3-day food records in IoM
and ALSPAC at an age of 7 years. Comparisons of mean daily nutrient, and food and
food group intakes were made between the studies and with UK national dietary
guidelines. Diets in both regions were adequate for most nutrients except dietary
fibre, but in both groups intake of free sugars was three times higher than the
UK recommended maximum. There were differences between the two regions,
particularly higher energy, protein, and carbohydrate intakes in IoM. IoM
children consumed greater amounts of red meat, bread, full-fat milk, and sugar
sweetened drinks. IoM children had higher intakes of energy and some nutrients
and food groups than ALSPAC children, and similar low intakes of fruits and
vegetables. Children's diets in both regions could be improved, particularly
considering the increasing prevalence of childhood obesity and the UK
recommendation to lower the intake of free sugars.
PMID- 28698479
TI - Antifungal Microbial Agents for Food Biopreservation-A Review.
AB - Food spoilage is a major issue for the food industry, leading to food waste,
substantial economic losses for manufacturers and consumers, and a negative
impact on brand names. Among causes, fungal contamination can be encountered at
various stages of the food chain (e.g., post-harvest, during processing or
storage). Fungal development leads to food sensory defects varying from visual
deterioration to noticeable odor, flavor, or texture changes but can also have
negative health impacts via mycotoxin production by some molds. In order to avoid
microbial spoilage and thus extend product shelf life, different treatments
including fungicides and chemical preservatives-are used. In parallel, public
authorities encourage the food industry to limit the use of these chemical
compounds and develop natural methods for food preservation. This is accompanied
by a strong societal demand for 'clean label' food products, as consumers are
looking for more natural, less severely processed and safer products. In this
context, microbial agents corresponding to bioprotective cultures, fermentates,
culture-free supernatant or purified molecules, exhibiting antifungal activities
represent a growing interest as an alternative to chemical preservation. This
review presents the main fungal spoilers encountered in food products, the
antifungal microorganisms tested for food bioprotection, and their mechanisms of
action. A focus is made in particular on the recent in situ studies and the
constraints associated with the use of antifungal microbial agents for food
biopreservation.
PMID- 28698481
TI - Plasma Neutrophil Gelatinase-Associated Lipocalin and Predicting Clinically
Relevant Worsening Renal Function in Acute Heart Failure.
AB - The aim of this study was to evaluate the ability of Neutrophil Gelatinase
Associated Lipocalin (NGAL) to predict clinically relevant worsening renal
function (WRF) in acute heart failure (AHF). Plasma NGAL and serum creatinine
changes during the first 4 days of admission were investigated in 1447 patients
hospitalized for AHF and enrolled in the Placebo-Controlled Randomized Study of
the Selective A1Adenosine Receptor Antagonist Rolofylline for Patients
Hospitalized with Acute Decompensated Heart Failure and Volume Overload to Assess
Treatment Effect on Congestion and Renal Function (PROTECT) study. WRF was
defined as serum creatinine rise >= 0.3 mg/dL through day 4. Biomarker patterns
were described using linear mixed models. WRF developed in 325 patients (22%).
Plasma NGAL did not rise earlier than creatinine in patients with WRF. After
multivariable adjustment, baseline plasma NGAL, but not creatinine, predicted
WRF. AUCs for WRF prediction were modest (<0.60) for all models. NGAL did not
independently predict death or rehospitalization (p = n.s.). Patients with WRF
and high baseline plasma NGAL had a greater risk of death, and renal or
cardiovascular rehospitalization by 60 days than patients with WRF and a low
baseline plasma NGAL (p for interaction = 0.024). A rise in plasma NGAL after
baseline was associated with a worse outcome in patients with WRF, but not in
patients without WRF (p = 0.007). On the basis of these results, plasma NGAL does
not provide additional, clinically relevant information about the occurrence of
WRF in patients with AHF.
PMID- 28698482
TI - Studying Autophagy in Zebrafish.
AB - Autophagy is an evolutionarily conserved catabolic process which allows lysosomal
degradation of complex cytoplasmic components into basic biomolecules that are
recycled for further cellular use. Autophagy is critical for cellular homeostasis
and for degradation of misfolded proteins and damaged organelles as well as
intracellular pathogens. The role of autophagy in protection against age-related
diseases and a plethora of other diseases is now coming to light; assisted by
several divergent eukaryotic model systems ranging from yeast to mice. We here
give an overview of different methods used to analyse autophagy in zebrafish-a
relatively new model for studying autophagy-and briefly discuss what has been
done so far and possible future directions.
PMID- 28698483
TI - Virtual Reality as a Promising Strategy in the Assessment and Treatment of
Bulimia Nervosa and Binge Eating Disorder: A Systematic Review.
AB - Several lines of evidence suggest that Virtual Reality (VR) has a potential
utility in eating disorders. The objective of this study is to review the
literature on the use of VR in bulimia nervosa (BN) and binge eating disorder
(BED). Using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta
Analyses) statement for reporting systematic reviews, we performed a PubMed, Web
of Knowledge and SCOPUS search to identify studies employing VR in the assessment
and treatment of BN and BED. The following search terms were used: "virtual
reality", "eating disorders", "binge eating", and "bulimia nervosa". From the 420
articles identified, 19 were selected, nine investigated VR in assessment and 10
were treatment studies (one case-report, two non-controlled and six randomized
controlled trials). The studies using VR in BN and BED are at an early stage.
However, considering the available evidence, the use of VR in the assessment of
those conditions showed some promise in identifying: (1) how those patients
experienced their body image; and (2) environments or specific kinds of foods
that may trigger binge-purging cycle. Some studies using VR-based environments
associated to cognitive behavioral techniques showed their potential utility in
improving motivation for change, self-esteem, body image disturbances and in
reducing binge eating and purging behavior.
PMID- 28698484
TI - Dual-energy X-ray Absorptiometry of Both Hips Helps Appropriate Diagnosis of Low
Bone Mineral Density and Osteoporosis.
AB - Controversy still remains regarding the use of bilateral hip scanning when bone
mineral density (BMD) is measured, and bilateral hip scanning is not mandatory in
international guidelines for screening of osteoporosis. BMD of both hips and the
lumbar spine was analyzed in 133 consecutive individuals. There were
discrepancies between the lowest T-scores of both hips. Fourteen of the 133
participants (11%) were diagnosed with a poorer BMD status when the BMD of the
hip of the dominant leg was analyzed. The total hip BMD of the dominant hip was
lower than in the non-dominant hip, (p = 0.035), whereas there were no
differences in the femoral neck area of the dominant and the non-dominant leg (p
= 0.754). When classified by Z- or T-scores, there was consistency in 60 cases
(45%) and inconsistency in 59 cases (44%). In 14 cases (11%), T- or Z-scores were
the same, and it did not matter whether the non-dominant hip or the dominant hip
had been chosen. A diagnostic discordance of 11% between the left and the right
hip was observed when the lumbar spine was evaluated. The lowest Z- and T-scores
of the hips were, in 44% of the cases, found in the hip of the assumed dominant
leg. BMD measurements of both hips are recommended as clinical practice.
PMID- 28698485
TI - Dynamic Fumonisin B2 Production by Aspergillus niger Intented Used in Food
Industry in China.
AB - There are a total of 30 strains including 27 strains of Aspergillus niger
intended used in Chinese food industry, two strains used as control and one
strain isolated from corn for fumonisin (FB) production on 3 media. It was found
that FB2 production by A. niger was function-dependent and highly related to
culture media, as well as incubation time. All strains studied were unable to
produce FB1 and FB3. Almost all strains were found to produce FB2 on corn, rice
and wheat bran. Based on their intended use in the food industry, the higher
level of FB2 producers were strains used for saccharifying enzyme (n = 13)
production, followed by organic acid (n = 6), tannase (n = 7) and beta
galactosidase (n = 1) production, with the FB2 mean level of 3553-10,270 MUg/kg,
1059-12,036 MUg/kg, 3-7 MUg/kg and 2-4 MUg/kg on corn, 5455-9241 MUg/kg, 559-2190
MUg/kg, 4-9 MUg/kg and 6-10 MUg/kg on rice, 5959-7709 MUg/kg, 9491-17,339 MUg/kg,
8-14 MUg/kg and 120-222 MUg/kg on wheat bran, respectively. Comparatively,
strains of Fusarium verticillioide were capable of producing fumonins
simultaneously with broader spectrum including FB1, FB2 and FB3, but at a much
lower level. In conclusion, it is necessary to evaluate FB2 production by A.
niger before intended use in the food processing industry.
PMID- 28698486
TI - Creativity Assessment in Subjects with Tourette Syndrome vs. Patients with
Parkinson's Disease: A Preliminary Study.
AB - (1) Background: Literature suggests that high levels of dopamine are associated
with creative thoughts. Tourette Syndrome (TS) patients have high dopamine
levels, while Parkinson's Disease (PD) subjects have low dopamine levels.
Consequently, TS individuals are supposed to have a major and PD patients less
creative output. Moreover, dopamine medications may alter the level of
creativity, and therefore Quality of Life, in both pathologies. (2) Methods: The
aim of the study was to verify the hypothesis of TS patients having higher
creative scores than PD patients. The assessment consisted of the administration
of the Creative Thinking ASK Test. There were 54 participants-36 males and 18
females-i.e., 27 TS patients and 27 PD subjects. Age of the sample was 35 to 57
years old, high school certificate was required. (3) Results: TS sample (103.11
ASK average score) was more creative than PD sample (94.11 ASK average score).
(4) Conclusions: The results supported the aforementioned hypothesis: TS sample
resulted in having higher creative scores than PD sample. Dopamine and other
neurotransmitters of TS and PS appear to affect subject's creativity. Further
studies with creative assessments in TS and PD patients are needed to support the
preliminary results of our study.
PMID- 28698487
TI - Multiple Mild Traumatic Brain Injuries Are Associated with Increased Rates of
Health Symptoms and Gulf War Illness in a Cohort of 1990-1991 Gulf War Veterans.
AB - Recent research demonstrated a relation between traumatic brain injury (TBI),
health symptoms and diagnosis of Gulf War Illness (GWI) in Gulf War Veterans, but
no study has examined the impact of multiple mild TBIs (mTBIs). A total of 229
male Gulf War Veterans from the Ft Devens Cohort were categorized by a number of
mTBIs reported. One-way ANOVA and chi-square test of independence were used to
test for differences in total reported health symptoms and diagnosis of chronic
multisymptom illness (CMI) or Kansas GWI criteria, two of the most common case
definitions of GWI. A total of 72 veterans reported no mTBIs (31.4%), 26 reported
one mTBI (11.4%), 25 reported two mTBIs (10.9%), and 106 veterans reported
sustaining three or more mTBIs (46.3%). Veterans reporting two or more mTBIs (p <
0.01) or three or more mTBIs (p < 0.001) endorsed significantly higher rates of
health symptoms than Veterans reporting no mTBIs. Significantly higher rates of
CMI (p = 0.035) and Kansas GWI criteria (p < 0.001) were seen in the three or
more mTBI group. Results suggest two mTBIs increase risk of health symptoms, but
three mTBIs may be the threshold needed to sustain chronic symptom reporting
needed for a formal diagnosis. These findings highlight the importance of
implementing policies and procedures monitoring head injuries in military
personnel.
PMID- 28698488
TI - Dementia at the End of Life and Family Partners: A Symbolic Interactionist
Perspective on Communication.
AB - People with dementia are not dying; they are experiencing changes in the brain.
This paper utilizes a symbolic interaction theoretical perspective to outline
communicative alternatives to polypharmacy. There is a growing interest in
sociological interventions to untangle the "disordered discourses" associated
with dementia. Such practices challenge common stigmas attached to dementia as an
"ongoing funeral" or "death certificate." Changing the expectations, attitudes
and communication patterns of family care partners can positively impact them and
the person living with dementia at the end of life. This paper delineates
multiple non-verbal communication interventions (e.g., the trip back in time,
dementia citizenship and sensory engagement modalities) to explore techniques to
engage persons with advanced dementia.
PMID- 28698489
TI - Dietary Vitamin C, E and beta-Carotene Intake Does Not Significantly Affect
Plasma or Salivary Antioxidant Indices and Salivary C-Reactive Protein in Older
Subjects.
AB - It is not clear whether habitual dietary intake influences the antioxidant or
inflammatory status. The aim of the present study was to assess the impact of
antioxidative vitamins C, E, and beta-carotene obtained from daily food rations
on plasma and salivary Total Antioxidant Capacity (TAC), uric acid and salivary C
reactive protein (CRP). The study involved 80 older subjects (66.9 +/- 4.3
years), divided into two groups: group 1 (n = 43) with lower and group 2 (n = 37)
with higher combined vitamins C, E and beta-carotene intake. A 24-h dietary
recall was obtained from each individual. TAC was assessed simultaneously with
two methods in plasma (Ferric Reducing Ability of Plasma-FRAP, 2.2-diphenyl-1
picryl-hydrazyl-DPPH) and in saliva (FRAS and DPPHS test). Lower vitamin C intake
corresponded to higher FRAS. There were no other correlations between vitamins C,
E or beta-carotene intake and antioxidant indices. Salivary CRP was not related
to any antioxidant indices. FRAS was decreased in group 2 (p < 0.01) but no other
group differences for salivary or for plasma antioxidant parameters and salivary
CRP were found. Habitual, not extra supplemented dietary intake does not
significantly affect plasma or salivary TAC and salivary CRP.
PMID- 28698490
TI - Birth Trends among Female Physicians in Taiwan: A Nationwide Survey from 1996 to
2013.
AB - Background: Although more and more women are becoming physicians, their decisions
regarding pregnancy may be affected by the lengthy period of medical education
and postgraduate training. The aim of this study was to explore the birth trends
among female physicians in Taiwan; Methods: Retrospective analyses of maternal
ages at delivery from 1996 to 2013, both for physicians and the general
population, were conducted using a nationwide dataset called National Health
Insurance Research Database; Results: During the study period, 8540 female
physicians were identified. The physicians delivered a total of 4940 births in
that time, with a rise from 210 in 1996 to 440 in 2013. In addition, the mean
maternal age of the physicians at delivery increased from 32.19 years (standard
deviations (SD) 2.80) in 1996 to 33.61 (SD 3.21) in 2013, values significantly
higher than those for non-physicians of 27.81 (SD 4.74) in 1996 (p < 0.001) and
31.36 (SD 4.78) in 2013 (p < 0.001); Conclusion: Female physicians usually gave
birth at an older age than non-physicians, but the discrepancy between the two
groups gradually declined over the 18-year course of the study. The establishment
of a maternity-friendly environment for female physicians should be considered by
those who determine healthcare system policies.
PMID- 28698491
TI - MicroRNA Signature of Human Microvascular Endothelium Infected with Rickettsia
rickettsii.
AB - MicroRNAs (miRNAs) mediate gene silencing by destabilization and/or translational
repression of target mRNA. Infection of human microvascular endothelial cells as
primary targets of Rickettsiarickettsii, the etiologic agent of Rocky Mountain
spotted fever, triggers host responses appertaining to alterations in cellular
gene expression. Microarray-based profiling of endothelial cells infected with
R.rickettsii for 3 or 24 h revealed differential expression of 33 miRNAs, of
which miRNAs129-5p, 200a-3p, 297, 200b-3p, and 595 were identified as the top
five up-regulated miRNAs (5 to 20-fold, p <= 0.01) and miRNAs 301b-3p, 548a-3p,
and 377-3p were down-regulated (2 to 3-fold, p <= 0.01). Changes in the
expression of selected miRNAs were confirmed by q-RT-PCR in both in vitro and in
vivo models of infection. As potential targets, expression of genes encoding
NOTCH1, SMAD2, SMAD3, RIN2, SOD1, and SOD2 was either positively or negatively
regulated. Using a miRNA-specific mimic or inhibitor, NOTCH1 was determined to be
a target of miRNA 200a-3p in R. rickettsii-infected human dermal microvascular
endothelial cells (HMECs). Predictive interactome mapping suggested the potential
for miRNA-mediated modulation of regulatory gene networks underlying important
host cell signaling pathways. This first demonstration of altered endothelial
miRNA expression provides new insights into regulatory elements governing
mechanisms of host responses and pathogenesis during human rickettsial
infections.
PMID- 28698492
TI - The Application of REDOR NMR to Understand the Conformation of Epothilone B.
AB - The structural information of small therapeutic compounds complexed in biological
matrices is important for drug developments. However, structural studies on
ligands bound to such a large and dynamic system as microtubules are still
challenging. This article reports an application of the solid-state NMR technique
to investigating the bioactive conformation of epothilone B, a microtubule
stabilizing agent, whose analog ixabepilone was approved by the U.S. Food and
Drug Administration (FDA) as an anticancer drug. First, an analog of epothilone B
was designed and successfully synthesized with deuterium and fluorine labels
while keeping the high potency of the drug; Second, a lyophilization protocol was
developed to enhance the low sensitivity of solid-state NMR; Third, molecular
dynamics information of microtubule-bound epothilone B was revealed by high
resolution NMR spectra in comparison to the non-bound epothilone B; Last,
information for the macrolide conformation of microtubule-bound epothilone B was
obtained from rotational-echo double-resonance (REDOR) NMR data, suggesting the X
ray crystal structure of the ligand in the P450epoK complex as a possible
candidate for the conformation. Our results are important as the first
demonstration of using REDOR for studying epothilones.
PMID- 28698493
TI - Antifungal and Antiochratoxigenic Activities of Essential Oils and Total Phenolic
Extracts: A Comparative Study.
AB - This study is intended to prevent ochratoxin A (OTA) production by Aspergillus
carbonarius S402 using essential oils (EOs) and total phenolic compounds
extracted from plants and herbs. The EOs used in this study are the following:
bay leaves, cumin, fenugreek, melissa, mint, and sage. As for the phenolic
compounds, they were extracted from bay leaves, cumin, fenugreek, melissa, mint,
sage, anise, chamomile, fennel, rosemary, and thyme. The experiments were
conducted on Synthetic Grape Medium (SGM) medium at 28 degrees C for 4 days. OTA
was extracted from the medium with methanol and quantified using HPLC (High
Performance Liquid Chromatography). Results showed that EOs had a greater impact
than the total phenolic extracts on the OTA production. Reduction levels ranged
between 25% (sage) and 80% (melissa) for the EOs at 5 uL mL-1, and 13% (thyme)
and 69% (mint) for the phenolic extracts. Although they did not affect the growth
of A. carbonarius, total phenolic extracts and EOs were capable of partially
reducing OTA production. Reduction levels depended on the nature of the plants
and the concentration of the EOs. Reducing OTA with natural extracts could be a
solution to prevent OTA production without altering the fungal growth, thus
preserving the natural microbial balance.
PMID- 28698494
TI - Fluorogenic Labeling Strategies for Biological Imaging.
AB - The spatiotemporal fluorescence imaging of biological processes requires
effective tools to label intracellular biomolecules in living systems. This
review presents a brief overview of recent labeling strategies that permits one
to make protein and RNA strongly fluorescent using synthetic fluorogenic probes.
Genetically encoded tags selectively binding the exogenously applied molecules
ensure high labeling selectivity, while high imaging contrast is achieved using
fluorogenic chromophores that are fluorescent only when bound to their cognate
tag, and are otherwise dark. Beyond avoiding the need for removal of unbound
synthetic dyes, these approaches allow the development of sophisticated imaging
assays, and open exciting prospects for advanced imaging, particularly for
multiplexed imaging and super-resolution microscopy.
PMID- 28698495
TI - Discovery of DNA Topoisomerase I Inhibitors with Low-Cytotoxicity Based on
Virtual Screening from Natural Products.
AB - Currently, DNA topoisomerase I (Topo I) inhibitors constitute a family of
antitumor agents with demonstrated clinical effects on human malignancies.
However, the clinical uses of these agents have been greatly limited due to their
severe toxic effects. Therefore, it is urgent to find and develop novel low toxic
Topo I inhibitors. In recent years, during our ongoing research on natural
antitumor products, a collection of low cytotoxic or non-cytotoxic compounds with
various structures were identified from marine invertebrates, plants, and their
symbiotic microorganisms. In the present study, new Topo I inhibitors were
discovered from low cytotoxic and non-cytotoxic natural products by virtual
screening with docking simulations in combination with bioassay test. In total,
eight potent Topo I inhibitors were found from 138 low cytotoxic or non-cytotoxic
compounds from coral-derived fungi and plants. All of these Topo I inhibitors
demonstrated activities against Topo I-mediated relaxation of supercoiled DNA at
the concentrations of 5-100 uM. Notably, the flavonoids showed higher Topo I
inhibitory activities than other compounds. These newly discovered Topo I
inhibitors exhibited structurally diverse and could be considered as a good
starting point for the development of new antitumor lead compounds.
PMID- 28698496
TI - Synthesis and Structure of the Inclusion Complex
{NdQ[5]K@Q[10](H2O)4}.4NO3.20H2O.
AB - Heating a mixture of Nd(NO3)3.6H2O, KCl, Q[10] and Q[5] in HCl for 10 min affords
the inclusion complex {NdQ[5]K@Q[10](H2O)4}.4NO3.20H2O. The structure of the
inclusion complex has been investigated by single crystal X-ray diffraction and
by X-ray Photoelectron spectroscopy (XPS).
PMID- 28698497
TI - Hardware/Software Data Acquisition System for Real Time Cell Temperature
Monitoring in Air-Cooled Polymer Electrolyte Fuel Cells.
AB - This work presents a hardware/software data acquisition system developed for
monitoring the temperature in real time of the cells in Air-Cooled Polymer
Electrolyte Fuel Cells (AC-PEFC). These fuel cells are of great interest because
they can carry out, in a single operation, the processes of oxidation and
refrigeration. This allows reduction of weight, volume, cost and complexity of
the control system in the AC-PEFC. In this type of PEFC (and in general in any
PEFC), the reliable monitoring of temperature along the entire surface of the
stack is fundamental, since a suitable temperature and a regular distribution
thereof, are key for a better performance of the stack and a longer lifetime
under the best operating conditions. The developed data acquisition (DAQ) system
can perform non-intrusive temperature measurements of each individual cell of an
AC-PEFC stack of any power (from watts to kilowatts). The stack power is related
to the temperature gradient; i.e., a higher power corresponds to a higher stack
surface, and consequently higher temperature difference between the coldest and
the hottest point. The developed DAQ system has been implemented with the low
cost open-source platform Arduino, and it is completed with a modular virtual
instrument that has been developed using NI LabVIEW. Temperature vs time
evolution of all the cells of an AC-PEFC both together and individually can be
registered and supervised. The paper explains comprehensively the developed DAQ
system together with experimental results that demonstrate the suitability of the
system.
PMID- 28698498
TI - Polar Grid Navigation Algorithm for Unmanned Underwater Vehicles.
AB - To solve the unavailability of a traditional strapdown inertial navigation system
(SINS) for unmanned underwater vehicles (UUVs) in the polar region, a polar grid
navigation algorithm for UUVs is proposed in this paper. Precise navigation is
the basis for UUVs to complete missions. The rapid convergence of Earth meridians
and the serious polar environment make it difficult to establish the true heading
of the UUV at a particular instant. Traditional SINS and traditional
representation of position are not suitable in the polar region. Due to the
restrictions of the complex underwater conditions in the polar region, a SINS
based on the grid frame with the assistance of the OCTANS and the Doppler
velocity log (DVL) is chosen for a UUV navigating in the polar region. Data
fusion of the integrated navigation system is realized by a modified fuzzy
adaptive Kalman filter (MFAKF). By neglecting the negative terms, and using T-S
fuzzy logic in the adaptive regulation of the noise covariance, the proposed
filter algorithm can improve navigation accuracy. Simulation and experimental
results demonstrate that the polar grid navigation algorithm can effectively
navigate a UUV sailing in the polar region.
PMID- 28698499
TI - Molecular Mechanisms behind Free Radical Scavengers Function against Oxidative
Stress.
AB - Accumulating evidence shows that oxidative stress is involved in a wide variety
of human diseases: rheumatoid arthritis, Alzheimer's disease, Parkinson's
disease, cancers, etc. Here, we discuss the significance of oxidative conditions
in different disease, with the focus on neurodegenerative disease including
Parkinson's disease, which is mainly caused by oxidative stress. Reactive oxygen
and nitrogen species (ROS and RNS, respectively), collectively known as RONS, are
produced by cellular enzymes such as myeloperoxidase, NADPH-oxidase (nicotinamide
adenine dinucleotide phosphate-oxidase) and nitric oxide synthase (NOS). Natural
antioxidant systems are categorized into enzymatic and non-enzymatic antioxidant
groups. The former includes a number of enzymes such as catalase and glutathione
peroxidase, while the latter contains a number of antioxidants acquired from
dietary sources including vitamin C, carotenoids, flavonoids and polyphenols.
There are also scavengers used for therapeutic purposes, such as 3,4
dihydroxyphenylalanine (L-DOPA) used routinely in the treatment of Parkinson's
disease (not as a free radical scavenger), and 3-methyl-1-phenyl-2-pyrazolin-5
one (Edaravone) that acts as a free radical detoxifier frequently used in acute
ischemic stroke. The cell surviving properties of L-DOPA and Edaravone against
oxidative stress conditions rely on the alteration of a number of stress proteins
such as Annexin A1, Peroxiredoxin-6 and PARK7/DJ-1 (Parkinson disease protein 7,
also known as Protein deglycase DJ-1). Although they share the targets in
reversing the cytotoxic effects of H2O2, they seem to have distinct mechanism of
function. Exposure to L-DOPA may result in hypoxia condition and further
induction of ORP150 (150-kDa oxygen-regulated protein) with its concomitant
cytoprotective effects but Edaravone seems to protect cells via direct induction
of Peroxiredoxin-2 and inhibition of apoptosis.
PMID- 28698500
TI - Use of Polycaprolactone Electrospun Nanofibers as a Coating for Poly(methyl
methacrylate) Bone Cement.
AB - Poly(methyl methacrylate) (PMMA) bone cement has limited biocompatibility.
Polycaprolactone (PCL) electrospun nanofiber (ENF) has many applications in the
biomedical field due to its excellent biocompatibility and degradability. The
effect of coating PCL ENF on the surface topography, biocompatibility, and
mechanical strength of PMMA bone cement is not currently known. This study is
based on the hypothesis that the PCL ENF coating on PMMA will increase PMMA
roughness leading to increased biocompatibility without influencing its
mechanical properties. This study prepared PMMA samples without and with the PCL
ENF coating, which were named the control and ENF coated samples. This study
determined the effects on the surface topography and cytocompatibility
(osteoblast cell adhesion, proliferation, mineralization, and protein adsorption)
properties of each group of PMMA samples. This study also determined the bending
properties (strength, modulus, and maximum deflection at fracture) of each group
of PMMA samples from an American Society of Testing Metal (ASTM) standard three
point bend test. This study found that the ENF coating on PMMA significantly
improved the surface roughness and cytocompatibility properties of PMMA (p <
0.05). This study also found that the bending properties of ENF-coated PMMA
samples were not significantly different when compared to those values of the
control PMMA samples (p > 0.05). Therefore, the PCL ENF coating technique should
be further investigated for its potential in clinical applications.
PMID- 28698501
TI - Energy Harvesting Based Body Area Networks for Smart Health.
AB - Body area networks (BANs) are configured with a great number of ultra-low power
consumption wearable devices, which constantly monitor physiological signals of
the human body and thus realize intelligent monitoring. However, the collection
and transfer of human body signals consume energy, and considering the comfort
demand of wearable devices, both the size and the capacity of a wearable device's
battery are limited. Thus, minimizing the energy consumption of wearable devices
and optimizing the BAN energy efficiency is still a challenging problem.
Therefore, in this paper, we propose an energy harvesting-based BAN for smart
health and discuss an optimal resource allocation scheme to improve BAN energy
efficiency. Specifically, firstly, considering energy harvesting in a BAN and the
time limits of human body signal transfer, we formulate the energy efficiency
optimization problem of time division for wireless energy transfer and wireless
information transfer. Secondly, we convert the optimization problem into a convex
optimization problem under a linear constraint and propose a closed-form solution
to the problem. Finally, simulation results proved that when the size of data
acquired by the wearable devices is small, the proportion of energy consumed by
the circuit and signal acquisition of the wearable devices is big, and when the
size of data acquired by the wearable devices is big, the energy consumed by the
signal transfer of the wearable device is decisive.
PMID- 28698502
TI - Rapid Surface Enhanced Raman Scattering (SERS) Detection of Sibutramine
Hydrochloride in Pharmaceutical Capsules with a beta-Cyclodextrin- Ag/Polyvivnyl
Alcohol Hydrogel Substrate.
AB - Sibutramine hydrochloride (SH) is a banned weight-loss drug, but its illegal
addition to health products is still rampant. This suggests a very urgent need
for a fast and precise detection method for SH. Surface Enhanced Raman Scattering
(SERS) is a promising candidate for this purpose, but the weak affinity between
SH and bare metal limits its direct SERS detection. In the present work, beta
cyclodextrin was capped in situ onto the surface of Ag nanoparticles to function
as a scaffold to capture SH. The obtained Ag nanoparticles were encapsulated into
polyvinyl alcohol (PVA) to fabricate a SERS active hydrogel with excellent
reproducibility. A facile SERS strategy based on such substrate was proposed for
trace SH quantification with a linear range of 7.0-150.0 ug.mL-1, and a detection
limit low to 3.0 ug.mL-1. It was applied to analyze seven types of commercial
slimming capsules with satisfactory results, showing good prospect for real
applications.
PMID- 28698503
TI - CD15s/CD62E Interaction Mediates the Adhesion of Non-Small Cell Lung Cancer Cells
on Brain Endothelial Cells: Implications for Cerebral Metastasis.
AB - Expression of the cell adhesion molecule (CAM), Sialyl Lewis X (CD15s) correlates
with cancer metastasis, while expression of E-selectin (CD62E) is stimulated by
TNF-alpha. CD15s/CD62E interaction plays a key role in the homing process of
circulating leukocytes. We investigated the heterophilic interaction of CD15s and
CD62E in brain metastasis-related cancer cell adhesion. CD15s and CD62E were
characterised in human brain endothelium (hCMEC/D3), primary non-small cell lung
cancer (NSCLC) (COR-L105 and A549) and metastatic NSCLC (SEBTA-001 and NCI-H1299)
using immunocytochemistry, Western blotting, flow cytometry and
immunohistochemistry in human brain tissue sections. TNF-alpha (25 pg/mL)
stimulated extracellular expression of CD62E while adhesion assays, under both
static and physiological flow live-cell conditions, explored the effect of CD15s
mAb immunoblocking on adhesion of cancer cell-brain endothelium. CD15s was
faintly expressed on hCMEC/D3, while high levels were observed on primary NSCLC
cells with expression highest on metastatic NSCLC cells (p < 0.001). CD62E was
highly expressed on hCMEC/D3 cells activated with TNF-alpha, with lower levels on
primary and metastatic NSCLC cells. CD15s and CD62E were expressed on lung
metastatic brain biopsies. CD15s/CD62E interaction was localised at adhesion
sites of cancer cell-brain endothelium. CD15s immunoblocking significantly
decreased cancer cell adhesion to brain endothelium under static and shear stress
conditions (p < 0.001), highlighting the role of CD15s-CD62E interaction in brain
metastasis.
PMID- 28698504
TI - Impact of Autophagy in Oncolytic Adenoviral Therapy for Cancer.
AB - Oncolytic virotherapy has recently emerged as a promising strategy for inducing
tumor-specific cell death. Adenoviruses are widely and frequently used in
oncolytic virotherapy. The mechanism of oncolytic adenovirus-mediated tumor
suppression involves virus-induced activation of the autophagic machinery in
tumor cells. Autophagy is a cytoprotective process that produces energy via
lysosomal degradation of intracellular components as a physiologic response to
various stresses, including hypoxia, nutrient deprivation, and disruption of
growth signaling. However, infection with oncolytic adenoviruses induces
autophagy and subsequent death of tumor cells rather than enhancing their
survival. In this review, we summarize the beneficial role of autophagy in
oncolytic adenoviral therapy, including the roles of infection, replication, and
cell lysis. Numerous factors are involved in the promotion and inhibition of
oncolytic adenovirus-mediated autophagy. Furthermore, recent evidence has shown
that oncolytic adenoviruses induce autophagy-related immunogenic cell death
(ICD), which enhances the antitumor immune response by inducing the activation of
danger signal molecules and thus represents a novel cancer immunotherapy.
Understanding the precise role of oncolytic adenovirus-induced autophagy and ICD
could enhance the therapeutic potential of oncolytic adenoviral therapy for
treating various cancers.
PMID- 28698505
TI - Retraction: Zhang, K., et al. Knockdown of Snail Sensitizes Pancreatic Cancer
Cells to Chemotherapeutic Agents and Irradiation. Int. J. Mol. Sci. 2010, 11,
4891-4904, doi:10.3390/ijms11124891 and Zhang, K., et al. RNA Interference
Targeting Slug Increases Cholangiocarcinoma Cell Sensitivity to Cisplatin via
Upregulating PUMA. Int. J. Mol. Sci. 2011, 12, 385-400, doi:10.3390/ijms12010385.
PMID- 28698506
TI - Ubiquitination in Periodontal Disease: A Review.
AB - Periodontal disease (periodontitis) is a chronic inflammatory condition initiated
by microbial infection that leads to gingival tissue destruction and alveolar
bone resorption. The periodontal tissue's response to dental plaque is
characterized by the accumulation of polymorphonuclear leukocytes, macrophages,
and lymphocytes, all of which release inflammatory mediators and cytokines to
orchestrate the immunopathogenesis of periodontal disease. Ubiquitination is
achieved by a mechanism that involves a number of factors, including an ubiquitin
activating enzyme, ubiquitin-conjugating enzyme, and ubiquitin-protein ligase.
Ubiquitination is a post-translational modification restricted to eukaryotes that
are involved in essential host processes. The ubiquitin system has been
implicated in the immune response, development, and programmed cell death.
Increasing numbers of recent reports have provided evidence that many approaches
are delivering promising reports for discovering the relationship between
ubiquitination and periodontal disease. The scope of this review was to
investigate recent progress in the discovery of ubiquitinated protein in diseased
periodontium and to discuss the ubiquitination process in periodontal diseases.
PMID- 28698507
TI - Risk Assessment of Mycotoxins in Stored Maize Grains Consumed by Infants and
Young Children in Nigeria.
AB - Maize is a major complimentary food for infants (0-4years) and young children (5
12years) in Nigeria. In this study, we assessed the risk of exposure of infants
and young children (IYC) to some major mycotoxins in stored maize grains from
five agro-ecological zones of Nigeria. The probable daily intake approach was
employed to determine exposure to five mycotoxins while the margin of exposure
(MOE) and population at risk of primary hepatocellular carcinoma approaches were
used to characterize the risk of consuming aflatoxin contaminated maize. Infants
and young children in the Derived Savannah zone are more exposed to aflatoxins,
ochratoxins, and zearalenone while those in the Northern Guinea Savanna zone are
mainly exposed to deoxynivalenol and fumonisins. The mean national MOE for
infants and children were 0.12 and 0.3 respectively while the risk of developing
primary liver cancer was estimated at 152.7 and 61.1 cancer/year/100,000
population of infants and children, respectively. Infants and young children
consuming mycotoxin contaminated maize in Nigeria are therefore vulnerable to the
adverse health effects. Mycotoxin contamination of maize is still a challenge in
Nigeria; mitigation efforts should target the value chain and stricter tolerable
limits should be enforced.
PMID- 28698508
TI - Jamaica's Critically Endangered Butterfly: A Review of the Biology and
Conservation Status of the Homerus Swallowtail (Papilio (Pterourus) homerus
Fabricius).
AB - The Homerus swallowtail, Papilio (Pterourus) homerus Fabricius, is listed as an
endangered species and is endemic to the Caribbean island of Jamaica. The largest
butterfly in the Western Hemisphere, P. homerus once inhabited seven of Jamaica's
14 parishes and consisted of at least three populations; however, now only two
stronghold populations remain, a western population in the rugged Cockpit Country
and an eastern population in the Blue and John Crow Mountains. Despite numerous
studies of its life history, much about the population biology, including
estimates of total numbers of individuals in each population, remains unknown. In
addition, a breeding program is needed to establish an experimental population,
which could be used to augment wild populations and ensure the continued survival
of the species. Here, we present a review of the biology of P. homerus and
recommendations for a conservation plan.
PMID- 28698509
TI - Almond Skin Extracts Abrogate HSV-1 Replication by Blocking Virus Binding to the
Cell.
AB - The aim of the present research was to determine the effect of almond skin
extracts on herpes simplex virus 1 (HSV-1) replication. Drug-resistant strains of
HSV frequently develop following therapeutic treatment. Therefore, the discovery
of novel anti-HSV drugs deserves great effort. Here, we tested both natural (NS)
and blanched (BS) polyphenols-rich almond skin extracts against HSV-1. HPLC
analysis showed that the prevalent compounds in NS and BS extracts contributing
to their antioxidant activity were quercetin, epicatechin and catechin. Results
of cell viability indicated that NS and BS extracts were not toxic to cultured
Vero cells. Furthermore, NS extracts were more potent inhibitors of HSV-1 than BS
extracts, and this trend was in agreement with different concentrations of
flavonoids. The plaque forming assay, Western blot and real-time PCR were used to
demonstrate that NS extracts were able to block the production of infectious HSV
1 particles. In addition, the viral binding assay demonstrated that NS extracts
inhibited HSV-1 adsorption to Vero cells. Our conclusion is that natural products
from almond skin extracts are an extraordinary source of antiviral agents and
provide a novel treatment against HSV-1 infections.
PMID- 28698510
TI - Genome Sequence of Pseudomonas stutzeri 273 and Identification of the
Exopolysaccharide EPS273 Biosynthesis Locus.
AB - Pseudomonas stutzeri 273 is a marine bacterium producing exopolysaccharide 273
(EPS273) with high anti-biofilm activity against P. aeruginosa PAO1. Here, the
complete genome of P.stutzeri 273 was sequenced and the genome contained a
circular 5.03 Mb chromosome. With extensive analysis of the genome, a genetic
locus containing 18 genes was predicted to be involved in the biosynthesis of
EPS273. In order to confirm this prediction, two adjacent genes (eps273-H and
eps273-I) encoding glycosyltransferases and one gene (eps273-O) encoding tyrosine
protein kinase within the genetic locus were deleted and biosynthesis of EPS273
was checked in parallel. The molecular weight profile of EPS purified from the
mutant Deltaeps273-HI was obviously different from that purified from wild-type
P.stutzeri 273, while the corresponding EPS was hardly detected from the mutant
Deltaeps273-O, which indicated the involvement of the proposed 18-gene cluster in
the biosynthesis of EPS273. Moreover, the mutant Deltaeps273-HI had the biofilm
formed earlier compared with the wild type, and the mutant Deltaeps273-O almost
completely lost the ability of biofilm formation. Therefore, EPS273 might
facilitate the biofilm formation for its producing strain P.stutzeri 273 while
inhibiting the biofilm formation of P. aeruginosa PAO1. This study can contribute
to better understanding of the biosynthesis of EPS273 and disclose the biological
function of EPS273 for its producing strain P.stutzeri 273.
PMID- 28698511
TI - The Effect of Silver Nanoparticles Size, Produced Using Plant Extract from
Arbutus unedo, on Their Antibacterial Efficacy.
AB - Silver nanoparticles (AgNPs) have been demonstrated to restrain bacterial growth,
while maintaining minimal risk in development of bacterial resistance and human
cell toxicity that conventional silver compounds exhibit. Several physical and
chemical methods have been reported to synthesize AgNPs. However, these methods
are expensive and involve heavy chemical reduction agents. An alternative
approach to produce AgNPs in a cost-effective and environmentally friendly way
employs a biological pathway using various plant extracts to reduce metal ions.
The size control issue, and the stability of nanoparticles, remain some of the
latest challenges in such methods. In this study, we used two different
concentrations of fresh leaf extract of the plant Arbutus unedo (LEA) as a
reducing and stabilizing agent to produce two size variations of AgNPs. UV-Vis
spectroscopy, Dynamic Light Scattering, Transmission Electron Microscopy, and
zeta potential were applied for the characterization of AgNPs. Both AgNP
variations were evaluated for their antibacterial efficacy against the gram
negative species Escherichia coli and Pseudomonas aeruginosa, as well as the gram
positive species Bacillus subtilis and Staphylococcus epidermidis. Although
significant differences have been achieved in the nanoparticles' size by varying
the plant extract concentration during synthesis, the antibacterial effect was
almost the same.
PMID- 28698512
TI - Eco-Friendly Acaricidal Effects of Nylon 66 Nanofibers via Grafted Clove Bud Oil
Loaded Capsules on House Dust Mites.
AB - Acaricidal nylon 66 fabrics (AN66Fs) grafted with clove oil-loaded microcapsules
(COMCs) were developed against Dermatophagoides farina (D. gallinae). The average
diameter was about 2.9 um with a range of 100 nm-8.5 um. COMCs carried clove oil
loading of about 65 vol %. COMCs were chemically grafted to electrospun nylon
nanofibers by the chemical reactions between -OH groups of COMCs and -COOH end
groups of nylon fabrics to form ester linkages. AN66Fs had an effect on D.
farinae depending on COMCs loadings. The increase in COMCs loading of AN66Fs from
5 to 15 wt % increased from 22% to 93% mortality against D. farinae within 72 h.
However, AN66Fs containing over 20 wt % COMCs were more effective, showing up to
100% mortality within 24 h because the large amount of monoterpene alcohol,
eugenol. This research suggests the use of clove oil and its major constituent
eugenol as eco-friendly bioactive agents that can serve as a replacement for
synthetic acaricides in controlling the population of D. farinae.
PMID- 28698513
TI - Anti-Inflammatory Activity of Citric Acid-Treated Wheat Germ Extract in
Lipopolysaccharide-Stimulated Macrophages.
AB - Until recently, fermentation was the only processing used to improve the
functionality of wheat germ. The release of 2,6-dimethoxy-1,4-benzoquinone (DMBQ)
from hydroquinone glycosides during the fermentation process is considered a
marker of quality control. Here, we treated wheat germ extract with citric acid
(CWG) to release DMBQ and examined the anti-inflammatory activity of this extract
using a lipopolysaccharide-activated macrophage model. Treatment of wheat germ
with citric acid resulted in detectable release of DMBQ but reduced total
phenolic and total flavonoid contents compared with untreated wheat germ extract
(UWG). CWG inhibited secretion of the pro-inflammatory cytokines tumor necrosis
factor-alpha, interleukin (IL)-6, and IL-12 and the synthesis of cyclooxygenase
2, while UWG only decreased IL-12 production. CWG and UWG induced high levels of
anti-inflammatory IL-10 and heme oxygenase-1. CWG specifically inhibited
phosphorylation of NF-kappaB p65 and p38 kinase at 15 min after LPS stimulation.
Our study showed that citric acid treatment enhanced the anti-inflammatory
activity of wheat germ extract.
PMID- 28698514
TI - Disinfection of the Water Borne Pathogens Escherichia coli and Staphylococcus
aureus by Solar Photocatalysis Using Sonochemically Synthesized Reusable Ag@ZnO
Core-Shell Nanoparticles.
AB - Water borne pathogens present a threat to human health and their disinfection
from water poses a challenge, prompting the search for newer methods and newer
materials. Disinfection of the Gram-negative bacterium Escherichia coli and the
Gram-positive coccal bacterium Staphylococcus aureus in an aqueous matrix was
achieved within 60 and 90 min, respectively, at 35 degrees C using solar
photocatalysis mediated by sonochemically synthesized Ag@ZnO core-shell
nanoparticles. The efficiency of the process increased with the increase in
temperature and at 55 degrees C the disinfection for the two bacteria could be
achieved in 45 and 60 min, respectively. A new ultrasound-assisted chemical
precipitation technique was used for the synthesis of Ag@ZnO core-shell
nanoparticles. The characteristics of the synthesized material were established
using physical techniques. The material remained stable even at 400 degrees C.
Disinfection efficiency of the Ag@ZnO core-shell nanoparticles was confirmed in
the case of real world samples of pond, river, municipal tap water and was found
to be better than that of pure ZnO and TiO2 (Degussa P25). When the nanoparticle-
based catalyst was recycled and reused for subsequent disinfection experiments,
its efficiency did not change remarkably, even after three cycles. The
sonochemically synthesized Ag@ZnO core-shell nanoparticles thus have a good
potential for application in solar photocatalytic disinfection of water borne
pathogens.
PMID- 28698515
TI - Post-Disaster Food and Nutrition from Urban Agriculture: A Self-Sufficiency
Analysis of Nerima Ward, Tokyo.
AB - Background: Post-earthquake studies from around the world have reported that
survivors relying on emergency food for prolonged periods of time experienced
several dietary related health problems. The present study aimed to quantify the
potential nutrient production of urban agricultural vegetables and the resulting
nutritional self-sufficiency throughout the year for mitigating post-disaster
situations. Methods: We estimated the vegetable production of urban agriculture
throughout the year. Two methods were developed to capture the production from
professional and hobby farms: Method I utilized secondary governmental data on
agricultural production from professional farms, and Method II was based on a
supplementary spatial analysis to estimate the production from hobby farms. Next,
the weight of produced vegetables [t] was converted into nutrients [kg].
Furthermore, the self-sufficiency by nutrient and time of year was estimated by
incorporating the reference consumption of vegetables [kg], recommended dietary
allowance of nutrients per capita [mg], and population statistics. The research
was conducted in Nerima, the second most populous ward of Tokyo's 23 special
wards. Self-sufficiency rates were calculated with the registered residents.
Results: The estimated total vegetable production of 5660 tons was equivalent to
a weight-based self-sufficiency rate of 6.18%. The average nutritional self
sufficiencies of Methods I and II were 2.48% and 0.38%, respectively, resulting
in an aggregated average of 2.86%. Fluctuations throughout the year were observed
according to the harvest seasons of the available crops. Vitamin K (6.15%) had
the highest self-sufficiency of selected nutrients, while calcium had the lowest
(0.96%). Conclusions: This study suggests that depending on the time of year,
urban agriculture has the potential to contribute nutrients to diets during post
disaster situations as disaster preparedness food. Emergency responses should be
targeted according to the time of year the disaster takes place to meet nutrient
requirements in periods of low self-sufficiency and prevent gastrointestinal
symptoms and cardiovascular diseases among survivors.
PMID- 28698516
TI - Exogenous Auxin Elicits Changes in the Arabidopsis thaliana Root Proteome in a
Time-Dependent Manner.
AB - Auxin is involved in many aspects of root development and physiology, including
the formation of lateral roots. Improving our understanding of how the auxin
response is mediated at the protein level over time can aid in developing a more
complete molecular framework of the process. This study evaluates the effects of
exogenous auxin treatment on the Arabidopsis root proteome after exposure of
young seedlings to auxin for 8, 12, and 24 h, a timeframe permitting the
initiation and full maturation of individual lateral roots. Root protein extracts
were processed to peptides, fractionated using off-line strong-cation exchange,
and analyzed using ultra-performance liquid chromatography and data independent
acquisition-based mass spectrometry. Protein abundances were then tabulated using
label-free techniques and evaluated for significant changes. Approximately 2000
proteins were identified during the time course experiment, with the number of
differences between the treated and control roots increasing over the 24 h time
period, with more proteins found at higher abundance with exposure to auxin than
at reduced abundance. Although the proteins identified and changing in levels at
each time point represented similar biological processes, each time point
represented a distinct snapshot of the response. Auxin coordinately regulates
many physiological events in roots and does so by influencing the accumulation
and loss of distinct proteins in a time-dependent manner. Data are available via
ProteomeXchange with the identifier PXD001400.
PMID- 28698517
TI - The Plasticity of Th17 Cells in the Pathogenesis of Rheumatoid Arthritis.
AB - Helper T (Th) cells play an important role in the pathogenesis of autoimmune
diseases, including rheumatoid arthritis (RA). It has been revealed that Th17
cells can shift to Th1 cells (i.e., "nonclassic Th1 cells"), which are reported
to be more pathogenic than Th17 cells per se. Thus, the association of Th cells
in the pathogenesis of autoimmune disease has become more complicated. We
recently reported using peripheral blood from untreated and early-onset RA
patients that the ratio of CD161+Th1 cells (i.e., Th17-derived Th1 cells to
CD161+Th17 cells) is elevated and that levels of interferon-gamma (IFNgamma)+Th17
cells are inversely correlated with levels of anti-CCP antibodies. Here, we
review the plasticity of Th17 cells in the pathogenesis of RA, suggesting
possible implications for novel therapies.
PMID- 28698518
TI - Challenges and Opportunities for Mainstreaming Climate Change Adaptation into
WaSH Development Planning in Ghana.
AB - Climate change threatens water, sanitation and hygiene (WaSH) facilities and
services, as these are intimately linked to the water cycle and are vulnerable to
changes in the quantity and quality of available water resources. Floods and
droughts, which pollute and reduce water delivery respectively, have now become a
perennial issue to deal with in the northern regions of Ghana. This study aimed
to assess the degree to which climate change adaptation measures are mainstreamed
into the water, sanitation and hygiene (WaSH) development planning process in
Ghana. Stakeholders from government and non-government agencies were interviewed
to gain perspectives on the threat of climate change, the inclusion of climate
change in WaSH planning and the barriers preventing mainstreaming. Despite
awareness of climate change, adaptation measures have not been considered, and
the immediate WaSH needs remain the priority. Overall, stakeholders felt the
adaptive capacity of the Municipality was low and that mainstreaming has not yet
occurred. Despite the lack of progress, there are great opportunities for
mainstreaming climate change adaptation into planning through increasing
awareness and capacity, legislative and institutional changes and the development
of participatory systems to provide early warning systems and disaster risk
analyses that will inform future planning.
PMID- 28698519
TI - Crystallization of Covalent Organic Frameworks for Gas Storage Applications.
AB - Covalent organic frameworks (COFs) have emerged as a new class of crystalline
porous materials prepared by integrating organic molecular building blocks into
predetermined network structures entirely through strong covalent bonds. The
consequently encountered "crystallization problem" has been conquered by dynamic
covalent chemistry in syntheses and reticular chemistry in materials design. In
this contribution, we have reviewed the progress in the crystallization of COF
materials and their hydrogen, methane and carbon dioxide gas storage properties
for clean energy applications.
PMID- 28698520
TI - The Polyketide Components of Waxes and the Cer-cqu Gene Cluster Encoding a Novel
Polyketide Synthase, the beta-Diketone Synthase, DKS.
AB - The primary function of the outermost, lipophilic layer of plant aerial surfaces,
called the cuticle, is preventing non-stomatal water loss. Its exterior surface
is often decorated with wax crystals, imparting a blue-grey color. Identification
of the barley Cer-c, -q and -u genes forming the 101 kb Cer-cqu gene cluster
encoding a novel polyketide synthase-the beta-diketone synthase (DKS), a
lipase/carboxyl transferase, and a P450 hydroxylase, respectively, establishes a
new, major pathway for the synthesis of plant waxes. The major product is a beta
diketone (14,16-hentriacontane) aliphatic that forms long, thin crystalline
tubes. A pathway branch leads to the formation of esterified alkan-2-ols.
PMID- 28698521
TI - Chromatin Dynamics in Genome Stability: Roles in Suppressing Endogenous DNA
Damage and Facilitating DNA Repair.
AB - Genomic DNA is compacted into chromatin through packaging with histone and non
histone proteins. Importantly, DNA accessibility is dynamically regulated to
ensure genome stability. This is exemplified in the response to DNA damage where
chromatin relaxation near genomic lesions serves to promote access of relevant
enzymes to specific DNA regions for signaling and repair. Furthermore, recent
data highlight genome maintenance roles of chromatin through the regulation of
endogenous DNA-templated processes including transcription and replication. Here,
we review research that shows the importance of chromatin structure regulation in
maintaining genome integrity by multiple mechanisms including facilitating DNA
repair and directly suppressing endogenous DNA damage.
PMID- 28698522
TI - Design, Synthesis, and Biological Activity of New Triazole and Nitro-Triazole
Derivatives as Antifungal Agents.
AB - In this study two series of fluconazole derivatives bearing nitrotriazole (series
A) or piperazine ethanol (series B) side chain were designed and synthesized and
then docked in the active site of lanosterol 14alpha-demethylase enzyme (1EA1)
using the Autodock 4.2 program (The scripps research institute, La Jolla, CA,
USA). The structures of synthesized compound were confirmed by various methods
including elemental and spectral (NMR, CHN, and Mass) analyses. Then antifungal
activities of the synthesized compound were tested against several natural and
clinical strains of fungi using a broth microdilution assay against several
standard and clinical fungi. Nitrotriazole derivatives showed excellent and
desirable antifungal activity against most of the tested fungi. Among the
synthesized compounds, 5a-d and 5g, possessing nitrotriazole moiety, showed
maximum antifungal activity, in particular against several fluconazole-resistant
fungi.
PMID- 28698523
TI - Assessing the Potential of Land Use Modification to Mitigate Ambient NO2 and Its
Consequences for Respiratory Health.
AB - Understanding how local land use and land cover (LULC) shapes intra-urban
concentrations of atmospheric pollutants-and thus human health-is a key component
in designing healthier cities. Here, NO2 is modeled based on spatially dense
summer and winter NO2 observations in Portland-Hillsboro-Vancouver (USA), and the
spatial variation of NO2 with LULC investigated using random forest, an ensemble
data learning technique. The NO2 random forest model, together with BenMAP, is
further used to develop a better understanding of the relationship among LULC,
ambient NO2 and respiratory health. The impact of land use modifications on
ambient NO2, and consequently on respiratory health, is also investigated using a
sensitivity analysis. We find that NO2 associated with roadways and tree-canopied
areas may be affecting annual incidence rates of asthma exacerbation in 4-12 year
olds by +3000 per 100,000 and -1400 per 100,000, respectively. Our model shows
that increasing local tree canopy by 5% may reduce local incidences rates of
asthma exacerbation by 6%, indicating that targeted local tree-planting efforts
may have a substantial impact on reducing city-wide incidence of respiratory
distress. Our findings demonstrate the utility of random forest modeling in
evaluating LULC modifications for enhanced respiratory health.
PMID- 28698524
TI - Telomerase Induction in HPV Infection and Oncogenesis.
AB - Telomerase extends the repetitive DNA at the ends of linear chromosomes, and it
is normally active in stem cells. When expressed in somatic diploid cells, it can
lead to cellular immortalization. Human papillomaviruses (HPVs) are associated
with and high-risk for cancer activate telomerase through the catalytic subunit
of telomerase, human telomerase reverse transcriptase (hTERT). The expression of
hTERT is affected by both high-risk HPVs, E6 and E7. Seminal studies over the
last two decades have identified the transcriptional, epigenetic, and post
transcriptional roles high-risk E6 and E7 have in telomerase induction. This
review will summarize these findings during infection and highlight the
importance of telomerase activation as an oncogenic pathway in HPV-associated
cancer development and progression.
PMID- 28698525
TI - Hepatoprotective Role of Hydrangea macrophylla against Sodium Arsenite-Induced
Mitochondrial-Dependent Oxidative Stress via the Inhibition of MAPK/Caspase-3
Pathways.
AB - Sodium arsenite (NaAsO2) has been recognized as a worldwide health concern.
Hydrangea macrophylla (HM) is used as traditional Chinese medicine possessing
antioxidant activities. The study was performed to investigate the therapeutic
role and underlying molecular mechanism of HM on NaAsO2-induced toxicity in human
liver cancer (HepG2) cells and liver in mice. The hepatoprotective role of HM in
HepG2 cells was assessed by using 3-(4,5-dimethylthiazol-2-Yl)-2,5
diphenyltetrazolium bromide (MTT), reactive oxygen species (ROS), and lactate
dehydrogenase (LDH) assays. Histopathology, lipid peroxidation, serum
biochemistry, quantitative real-time polymerase chain reaction (qPCR) and Western
blot analyses were performed to determine the protective role of HM against
NaAsO2 intoxication in liver tissue. In this study, we found that co-treatment
with HM significantly attenuated the NaAsO2-induced cell viability loss,
intracellular ROS, and LDH release in HepG2 cells in a dose-dependent manner.
Hepatic histopathology, lipid peroxidation, and the serum biochemical parameters
alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were notably
improved by HM. HM effectively downregulated the both gene and protein expression
level of the mitogen-activated protein kinase (MAPK) cascade. Moreover, HM well
regulated the Bcl-2-associated X protein (Bax)/B-cell lymphoma-2 (Bcl-2) ratio,
remarkably suppressed the release of cytochrome c, and blocked the expression of
the post-apoptotic transcription factor caspase-3. Therefore, our study provides
new insights into the hepatoprotective role of HM through its reduction in
apoptosis, which likely involves in the modulation of MAPK/caspase-3 signaling
pathways.
PMID- 28698526
TI - Altered Mitochondrial Metabolism and Mechanosensation in the Failing Heart: Focus
on Intracellular Calcium Signaling.
AB - The heart consists of millions of cells, namely cardiomyocytes, which are highly
organized in terms of structure and function, at both macroscale and microscale
levels. Such meticulous organization is imperative for assuring the physiological
pump-function of the heart. One of the key players for the electrical and
mechanical synchronization and contraction is the calcium ion via the well-known
calcium-induced calcium release process. In cardiovascular diseases, the
structural organization is lost, resulting in morphological, electrical, and
metabolic remodeling owing the imbalance of the calcium handling and promoting
heart failure and arrhythmias. Recently, attention has been focused on the role
of mitochondria, which seem to jeopardize these events by misbalancing the
calcium processes. In this review, we highlight our recent findings, especially
the role of mitochondria (dys)function in failing cardiomyocytes with respect to
the calcium machinery.
PMID- 28698527
TI - Engineering of a Potent Recombinant Lectin-Toxin Fusion Protein to Eliminate
Human Pluripotent Stem Cells.
AB - The use of human pluripotent stem cells (hPSCs) such as human embryonic stem
cells (hESCs) and human induced pluripotent stem cells (hiPSCs) in regenerative
medicine is hindered by their tumorigenic potential. Previously, we developed a
recombinant lectin-toxin fusion protein of the hPSC-specific lectin rBC2LCN,
which has a 23 kDa catalytic domain (domain III) of Pseudomonas aeruginosa
exotoxin A (rBC2LCN-PE23). This fusion protein could selectively eliminate hPSCs
following its addition to the cell culture medium. Here we conjugated rBC2LCN
lectin with a 38 kDa domain of exotoxin A containing domains Ib and II in
addition to domain III (PE38). The developed rBC2LCN-PE38 fusion protein could
eliminate 50% of 201B7 hPSCs at a concentration of 0.003 MUg/mL (24 h
incubation), representing an approximately 556-fold higher activity than rBC2LCN
PE23. Little or no effect on human fibroblasts, human mesenchymal stem cells, and
hiPSC-derived hepatocytes was observed at concentrations lower than 1 MUg/mL.
Finally, we demonstrate that rBC2LCN-PE38 selectively eliminates hiPSCs from a
mixed culture of hiPSCs and hiPSC-derived hepatocytes. Since rBC2LCN-PE38 can be
prepared from soluble fractions of E. coli culture at a yield of 9 mg/L, rBC2LCN
PE38 represents a practical reagent to remove human pluripotent stem cells
residing in cultured cells destined for transplantation.
PMID- 28698528
TI - Inflammatory and Noninflammatory Itch: Implications in Pathophysiology-Directed
Treatments.
AB - Itch is the main chief complaint in patients visiting dermatologic clinics and
has the ability to deeply impair life quality. Itch results from activation of
cutaneous nerve endings by noxious stimuli such as inflammatory mediators,
neurotransmitters and neuropeptides, causing itch signal transduction from
peripheral skin, through the spinal cord and thalamus, to the brain cortex.
Primarily noninflammatory diseases, such as uremic pruritus, cause itch through
certain pruritogens in the skin. In inflammatory skin diseases, atopic dermatitis
(AD) is the prototypic disease causing intensive itch by aberrant skin
inflammation and epidermal barrier disruption. Recent understanding of disease
susceptibility, severity markers, and mechanisms have helped to develop targeted
therapy for itch in AD, including monoclonal antibodies against IL-4, IL-13,
thymic stromal lymphopoietin (TSLP), IgE and IL-31. Promising effects have been
observed in some of them. In this review, we summarized targeted therapies for
inflammatory itch in AD and for managing abnormal itch transductions in other
common itching skin diseases.
PMID- 28698529
TI - Naturally Occurring Compounds: New Potential Weapons against Oxidative Stress in
Chronic Kidney Disease.
AB - Oxidative stress is a well-described imbalance between the production of reactive
oxygen species (ROS) and the antioxidant defense system of cells and tissues. The
overproduction of free radicals damages all components of the cell (proteins,
lipids, nucleic acids) and modifies their physiological functions. As widely
described, this condition is a biochemical hallmark of chronic kidney disease
(CKD) and may dramatically influence the progression of renal impairment and the
onset/development of major systemic comorbidities including cardiovascular
diseases. This state is exacerbated by exposure of the body to uremic toxins and
dialysis, a treatment that, although necessary to ensure patients' survival,
exposes cells to non-physiological contact with extracorporeal circuits and
membranes with consequent mitochondrial and anti-redox cellular system
alterations. Therefore, it is undeniable that counteracting oxidative stress
machinery is a major pharmacological target in medicine/nephrology. As a
consequence, in recent years several new naturally occurring compounds,
administered alone or integrated with classical therapies and an appropriate
lifestyle, have been proposed as therapeutic tools for CKD patients. In this
paper, we reviewed the recent literature regarding the "pioneering" in vivo
testing of these agents and their inclusion in small clinical trials performed in
patients affected by CKD.
PMID- 28698530
TI - The Role of miRNAs in Angiogenesis, Invasion and Metabolism and Their Therapeutic
Implications in Gliomas.
AB - MicroRNAs (miRNAs) are small, non-coding, endogenous RNA molecules that function
in gene silencing by post-transcriptional regulation of gene expression. The
dysregulation of miRNA plays a pivotal role in cancer tumorigenesis, including
the development and progression of gliomas. Their small size, stability and
ability to target multiple oncogenes have simultaneously distinguished miRNAs as
attractive candidates for biomarkers and novel therapeutic targets for glioma
patients. In this review, we summarize the most frequently cited miRNAs known to
contribute to gliomagenesis and progression by regulating the defining hallmarks
of gliomas, including angiogenesis, invasion, and cell metabolism. We also
discuss their promising potential as prognostic and predictive biomarkers and
novel therapeutic targets, in addition to the challenges that must be overcome
before their translation from bench to bedside.
PMID- 28698531
TI - Microfluidic Platform for the Long-Term On-Chip Cultivation of Mammalian Cells
for Lab-On-A-Chip Applications.
AB - Lab-on-a-Chip (LoC) applications for the long-term analysis of mammalian cells
are still very rare due to the lack of convenient cell cultivation devices. The
difficulties are the integration of suitable supply structures, the need of
expensive equipment like an incubator and sophisticated pumps as well as the
choice of material. The presented device is made out of hard, but non-cytotoxic
materials (silicon and glass) and contains two vertical arranged membranes out of
hydrogel. The porous membranes are used to separate the culture chamber from two
supply channels for gases and nutrients. The cells are fed continuously by
diffusion through the membranes without the need of an incubator and low
requirements on the supply of medium to the assembly. The diffusion of oxygen is
modelled in order to find the optimal dimensions of the chamber. The chip is
connected via 3D-printed holders to the macroscopic world. The holders are coated
with Parlyene C to ensure that only biocompatible materials are in contact with
the culture medium. The experiments with MDCK-cells show the successful seeding
inside the chip, culturing and passaging. Consequently, the presented platform is
a step towards Lab-on-a-Chip applications that require long-term cultivation of
mammalian cells.
PMID- 28698532
TI - A Smartphone-Based Automatic Measurement Method for Colorimetric pH Detection
Using a Color Adaptation Algorithm.
AB - This paper proposes a smartphone-based colorimetric pH detection method using a
color adaptation algorithm for point-of-care applications. Although a smartphone
camera can be utilized to measure the color information of colorimetric sensors,
ambient light changes and unknown built-in automatic image correction operations
make it difficult to obtain stable color information. This paper utilizes a 3D
printed mini light box and performs a calibration procedure with a paper-printed
comparison chart and a reference image which overcomes the drawbacks of
smartphone cameras and the difficulty in preparing for the calibration procedure.
The color adaptation is performed in the CIE 1976 u'v' color space by using the
reference paper in order to stabilize the color variations. Non-rigid u'v' curve
interpolation is used to produce the high-resolution pH estimate. The final pH
value is estimated by using the best-matching method to handle the nonlinear
curve properties of multiple color patches. The experimental results obtained
using a pH indicator paper show that the proposed algorithm provides reasonably
good estimation of pH detection. With paper-printed accurate color comparison
charts and smart color adaptation techniques, superior estimation is achieved in
the smartphone-based colorimetric pH detection system for point-of-care
application.
PMID- 28698533
TI - Prevention and Management of Cow's Milk Allergy in Non-Exclusively Breastfed
Infants.
AB - Introduction: The prevention and management of cow milk allergy (CMA) is still
debated. Since CMA is much less frequent in breastfed infants, breastfeeding
should be stimulated. Method: Literature was searched using databases to find
original papers and reviews on this topic. Results: Hydrolysates with a clinical
proof of efficacy are recommended in the prevention and treatment of CMA.
However, not all meta-analyses conclude that hydrolysates do prevent CMA or other
atopic manifestations such as atopic dermatitis. There are pros and cons to
consider partially hydrolysed protein as an option for starter infant formula for
each non-exclusively breastfed infant. A challenge test is still recommended as
the most specific and sensitive diagnostic test, although a positive challenge
test does not proof that the immune system is involved. The Cow Milk Symptom
Score (CoMiSSTM) is an awareness tool that enables healthcare professionals to
better recognize symptoms related to the ingestion of cow milk, but it still
needs validation as diagnostic tool. The current recommended elimination diet is
a cow milk based extensive hydrolysate, although rice hydrolysates or soy infant
formula can be considered in some cases. About 10 to 15% of infants allergic to
cow milk will also react to soy. Mainly because of the higher cost, amino acid
based formula is reserved for severe cases. There is no place for infant formula
with intact protein from other animals as cross-over allergenicity is high.
During recent years, attention focused also on the bifidogenic effect of
prebiotics and more recently also on human milk oligosaccharides. A bifidogenic
gastrointestinal microbiome may decrease the risk to develop allergic disease.
The addition of probiotics and prebiotics to the elimination diet in treatment
may enhance the development of tolerance development. Conclusion: Breastfeeding
is the best way to feed infants. Cow milk based extensive hydrolysates remain the
first option for the treatment of CMA for the majority of patients, while amino
acid formulas are reserved for the most severe cases. Rice hydrolysates and soy
infant formula are second choice options. Partial hydrolysates with clinical
proof of efficacy are recommended in some guidelines in the prevention of CMA and
allergic disease in at risk infants, and may be considered as an option as
protein source in starter infant formula.
PMID- 28698534
TI - The effect of functional insulin therapy on glycaemic parameters in children with
diabetes mellitus type 1.
AB - Aim The aim of the study is to evaluate the effect of a prospectively conducted
interactive 5-day education programme based on Dusseldorf model on glycated
haemoglobin (A1C), and total daily dose of insulin in type 1 diabetes patients.
Methods A total of 67 type 1 diabetes patients was analysed; mean age of 11+/
0.68 years, 43 females and 24 males. The programme was led by a trained team of
diabetes specialist doctors and nurses. All subjects and their parents completed
a knowledge test about diabetes at beginning, and at the end of education, and
after 12 months (30 questions). Subjects were evaluated for total daily insulin,
and HbA1c at baseline, as well as 3, 6, 9 and 12 months after the end of the
education programme. Results Results of the knowledge test after the education
have shown higher knowledge at baseline. At the end of the education programme an
average of total daily insulin dose was significantly lower. There was a 3.17%
reduction in HbA1c values over 9 months, and 1.8% over 12 months in the
comparison to the baseline values (p<0.001). Conclusions Structured education
programme of functional insulin therapy was associated with improved glycaemic
control in type 1 diabetes patients and their parents. It motivated patients and
parents to improve glycaemic control. One year after the follow up, glycaemic
control was worsening, due to lack of patients' motivation, therefore, there is a
need for yearly re-education.
PMID- 28698535
TI - Is post-treatment standardized uptake value a prognostic factor in unresectable
non-small cell lung carcinoma?
AB - Aim Concurrent chemoradiotherapy (CRT) is the standard of care for locally
advanced, unresectable non-small cell lung carcinoma (NSCLC). The aim of this
study was to assess the prognostic value of maximum standardized uptake values
(SUVmax) in patients with unresectable stage III NSCLC treated with concurrent
CRT. Method 18F-FDG PET-CT scans were obtained before and after treatment in
patients with unresectable stage III NSCLC treated with concurrent CRT. To
determine the prognostic value of SUVmax of the primary tumor (PT), univariate
and multivariate Cox regression model were carried out. Results Between January
2008 and December 2013, this study included 43 patients (median age 56 years, 95%
male). Univariate analysis showed that having a high post-treatment PT-SUVmax was
associated with a higher risk of death and having a high post-treatment PT-SUVmax
with a higher risk of disease recurrence. Multivariate analysis showed that
having a low post-treatment PTSUVmax (cut off 3.9) was associated with longer
overall and progression free survival (HR 8.55, 95% CI; 2.56-28.55, p=0.000 and
HR 2.854, 95% CI; 1.43-5.67, p=0.003, respectively). Conclusion Post-treatment PT
SUVmax may be an independent prognostic factor in patients with unresectable
stage III NSCLC treated with concurrent chemoradiotherapy.
PMID- 28698536
TI - Metformin use associated with lower risk of cancer in patients with diabetes
mellitus type 2.
AB - Aim In order to increase the database related to the antineoplastic potential of
metformin, association between the use of metformin and risk of cancer occurence
in patients with diabetes mellitus type 2 (DM2) was investigated. Methods In this
cross-sectional study, medical records of patients with DM2 were reviewed for
cancer occurence. Data on age, body mass index (BMI), alcohol and nicotine
consumption, glucose and HbA1c levels, duration of DM2, medication used in the
treatment of DM2 and cancer occurence were collected and analyzed. Unpaired
Student's t-test or Mann-Whitney U test were used for comparisons between
treatment groups, and logistic regression to asses how well our set of predictor
variables predicts occurence of carcinoma. P-value less than 0.05 was considered
statistically significant. Results The mean age of 234 included patients was
66.8+/-11.5 years, and DM2 duration was 7+/- 6.49 years. Mean glucose value was
8.51+/-4.17mmol/L, and HbA1c 7.74+/-1.53. Metformin therapy was prescribed in 190
(81%) patients. Cancer was diagnosed in 16 (6.8%) patients: prostate cancer in
eight (3.4%), breast cancer in four (1.7%), rectal cancer in two (0.9%) and
cancer of the uterus and cervix in one patient. Age, duration of DM2 and BMI did
not contribute significantly to the model, while metformin use was shown to be a
significant independent predictor (OR=0.049; 95% CI=0.013-0.181; p=0.001).
Conclusion Our findings support the hypothesis that the use of metformin compared
to the use of other oral antidiabetic drugs is associated with a lower risk of
cancer in patients with DM2.
PMID- 28698537
TI - Positron emission tomography/computed tomography (PET/CT) and CT for N staging of
non-small cell lung cancer.
AB - Aim The aim of this study is to investigate the possibilities of non-invasive
diagnostic imaging methods, positron emission tomography/computed tomography
(PET/CT) and CT, in clinical N staging of non-small cell lung cancer (NSCLC).
Methods Retrospective clinical study included 50 patients with diagnosed NSCLC
who have undergone PET/CT for the purpose of disease staging. The International
association for the study of lung cancer (IASLC) nodal mapping system was used
for analysis of nodal disease. Data regarding CT N-staging and PET/CT Nstaging
were recorded. Two methods were compared using chi2 test and Spearman rank
correlation coefficient. Results Statistical analysis showed that although there
were some differences in determining the N stage between CT and PET/CT, these
methods were in significant correlation. CT and PET/CT findings established the
same N stage in 74% of the patients. In five patients based on PET/CT findings
the staging was changed from operable to inoperable, while in four patients
staging was changed from inoperable to operable. Conclusion PET/CT and CT are
noninvasive methods that can be reliably used for N staging of NSCLC.
PMID- 28698538
TI - Warfarin should not be used for thromboprohylaxis in elective major orthopaedic
surgery: a Croatian perspective.
AB - Aim To identify modes of venous thromboembolism (VTE) prophylaxis in patients
undergoing elective major orthopaedic surgery (total hip or knee arthroplasty,
THA/TKA) at a single university-associated hospital in Croatia. Methods A
retrospective analysis of consecutive patients subjected to THA or TKA over a two
year period (2014-2015) with a focus on anticoagulation during the first 15 post
surgical days (period of highest VTE risk). Results Of 603 identified patients
three (0.5%) were not anticoagulated (haemophilia) and others received
perioperative doses of low molecular weight heparins (LMWH). Overall, 228 (37.8%)
patients received prophylaxis not involving warfarin, and 372 continued with
short-term LMWH with switching to warfarin. They contributed a total of 1218
international normalized ratio (INR) values (median=3, range=1-8). These were
consistently below the target INR range across the observed period. Between post
surgical days 6 and 15 (after the initial titration), 438 values were taken in
patients treated with LMWH+warfarin and 92.7% were below, and only 6.8% within
the target range; 580 values were taken in patients already switched to warfarin,
74% were below and only 25% within the range. Conclusion The prevailing mode of
VTE prophylaxis was in a clear contrast to (then) actual professional guidelines,
with inadequate monitoring and poor anticoagulation. There is no reason to expect
a substantially different situation at other institutions across the country. The
prevailing practice of VTE prophylaxis in major orthopaedic surgery in Croatia
should be promptly abandoned and up-dated in agreement with the current state of
the art.
PMID- 28698539
TI - Croatian rotatory oblique three-dimensional osteotomy (CROTO) - a modified
Wilson's osteotomy for adult hallux valgus intended to prevent dorsal
displacement of the distal fragment and to reduce shortening of the first
metatarsal bone.
AB - Aim To evaluate biomechanical and clinical outcomes of a newly developed
modification of the Wilson's osteotomy for hallux valgus: a three-dimensional
subcaptial correction of the metatarsal head position with a simultaneous lateral
and plantar shift with derotation intended to reduce displacement of the distal
fragment and shortening of the first metatarsal bone. Methods Thirty four feet
(28 female patients) underwent the new procedure and were evaluated before and 12
to 84 months (median=25.5) after the surgery. Results Plantar shift of the distal
fragment was achieved in all feet. Shortening of the first metatarsal was
moderate: <=6 mm in 32/34 feet, 7 and 10 mm in the remaining two. Median
difference in metatarsal index post- vs. pretreatment was -4.0. The hallux valgus
angle, intermetatarsal and distal metatarsal articular angles were reduced in all
feet. The American Orthopaedic Foot and Ankle Society score improved in all feet
(median increase= 51.5). Conclusion The method allows for a lateral and plantar
shift with derotation of the distal fragment and a mild/moderate shortening of
the first metatarsal bone.
PMID- 28698540
TI - Epigallocatechin Gallate Attenuates Hip Fracture-Induced Acute Lung Injury by
Limiting Mitochondrial DNA (mtDNA) Release.
AB - BACKGROUND To study the protective effects and explore the mechanism of
epigallocatechingallate (EGCG) on the hip fracture-induced acute lung injury.
MATERIAL AND METHODS Thirty male Sprague-Dawley (SD) rats were randomly divided
into the control group, hip fracture group, and hip fracture + EGCG (10 mg/Kg)
group. After 24 h, blood samples, bronchoalveolar lavage fluid (BALF), and lung
tissue were collected. Serum mitochondrial DNA (mtDNA) was measured by RT-PCR and
BALF was used to perform cytological analysis and enzyme-linked immunosorbent
assay (ELISA) assay. Lung tissue was used to evaluate the injury level. RESULTS
EGCG significantly reduced the hip fracture-induced high level of serum mtDNA
(p<0.05). HE staining showed protective effects of EGCG. Lower lung injury score
and wet/dry ratio were identified in the hip fracture + EGCG group than in the
hip fracture group (p<0.05). We found significantly lower levels of infiltration
of inflammatory cells and production of inflammatory cytokines in the BALF of the
hip fracture + EGCG group than in the hip fracture group (p<0.05). CONCLUSIONS
Our study found that EGCG had protective effects on hip fracture-induced acute
lung injury and suggests that EGCG exerts its protective effects through limiting
the release of mtDNA. Our results provide a novel pharmacological agent to
attenuate hip fracture-induced acute lung injury, as well as a potential theory
to better explain the anti-inflammatory property of EGCG.
PMID- 28698541
TI - Ataxia Telangiectasia in Siblings: Oral Motor and Swallowing Characterization.
AB - BACKGROUND The body of literature on oral motor and swallowing disorders in
patients with ataxia telangiectasia (AT) is limited. CASE REPORT The purpose of
this study was to characterize oral motor and swallowing disorders in two
siblings with AT, based on oral motor and swallowing assessments. Specific
procedures were applied for oral motor and swallowing assessments and both
patients underwent videofluoroscopy (VFS). Case 1 presented vocal instability,
change in postural control during feeding; food retention in oral cavity; slower
oral transit time; and multiple swallowing (signs for solid and liquid). Case 2
presented parted lips at rest and reduced muscle strength; reduced strength and
mobility of the tongue; vocal weakness and instability; reduced speech precision
and intelligibility; decreased intonation pattern; food retention in oral cavity
during feeding; slower oral transit time; multiple swallowing (signs for solid
and liquid); poor bolus ejection; incoordination and difficulty in controlling
the sips of water taken from the cup; altered cervical auscultation after
swallowing and respiratory distress (liquid and puree). For both patients VFS
results revealed laryngeal penetration for liquid. CONCLUSIONS Although the
literature describes the occurrence of dysarthria and swallowing disorders in
patients with AT, little attention has been given to describing which oral motor
deficits are responsible for these disorders. Early identification of swallowing
alterations and rehabilitation could decrease the risk of aspiration pneumonia.
Future studies are necessary in order to investigate the deterioration process of
swallowing in AT and the influence of rehabilitation in maintaining functional
health.
PMID- 28698542
TI - Genome-wide differential mRNA expression profiles in follicles of two breeds and
at two stages of estrus cycle of gilts.
AB - Estrus expression by gilts and sows is hereditable and important for heat
detection. To better understand the molecular biological mechanisms of estrus
expression in gilts, the mRNA expression profiles of follicular tissue from Large
White gilts in diestrus (LD, n = 3) and estrus (LE, n = 3), and Chinese
indigenous Mi gilts in diestrus (MD, n = 2) and estrus (ME, n = 3) were
investigated using RNA sequencing. We detected 122,804-335,295 SNPs, 6,140-14,947
InDel and 12 types of AS events (39.57% TSS, 34.90% TTS) in 11 samples. A total
of 2,838 differentially expressed genes (DEGs) were found in LD vs MD, LE vs ME,
LE vs LD, or ME vs MD comparisons. Two DEGs (ACP5 and PIGS) were observed in all
comparisons. Two new genes (ENSSSCG00000028235 and ENSSSCG00000021903) were
exclusively expressed in Mi and Large White gilts, respectively. Bioinformatics
analyses indicate that these DEGs are involved in single-organism process,
catalytic activity, cell adhesion and enriched in ECM-receptor interaction,
olfactory transduction, ovarian steroidogenesis, steroid biosynthesis and CAMs
signaling pathways. These results of RNA-Seq have provided important information
for screening the key functional genes or molecular markers of estrus expression
in gilts.
PMID- 28698543
TI - Genistein Protects Genioglossus Myoblast Against Hypoxia-induced Injury through
PI3K-Akt and ERK MAPK Pathways.
AB - Obstructive sleep apnea and hypopnea syndrome (OSAHS) is a clinical syndrome
characterized by recurrent episodes of obstruction of the upper airway during
sleep that leads to a hypoxic condition. Genioglossus, an important pharyngeal
muscle, plays an important role in maintaining an open upper airway for effective
breathing. Our previous study found that genistein (a kind of phytoestrogen)
protects genioglossus muscle from hypoxia-induced oxidative injury. However, the
underlying mechanism is still unknown. In the present study, we examined the
effects of hypoxia on genioglossus myoblast proliferation, viability and
apoptosis, and the protective effect of genistein and its relationship with the
PI3K/Akt and ERK MAPK pathways. Cell viability and Bcl-2 were reduced under
hypoxic condition, while ROS generation, caspase-3, MDA, and DNA damage were
increased following a hypoxia exposure. However, the effects of hypoxia were
partially reversed by genistein in an Akt- and ERK- (but not estrogen receptor)
dependent manner. In conclusion, genistein protects genioglossus myoblasts
against hypoxia-induced oxidative injury and apoptosis independent of estrogen
receptor. The PI3K-Akt and ERK1/2 MAPK signaling pathways are involved in the
antioxidant and anti-apoptosis effect of genistein on genioglossus myoblasts.
PMID- 28698544
TI - Dynamics and extreme plasticity of metallic microparticles in supersonic
collisions.
AB - Metallic microparticles can acquire remarkable nanoscale morphologies after
experiencing high velocity collisions, but materials science regarding the
extreme events has been limited due to a lack of controlled experiments. In this
work, collision dynamics and nonlinear material characteristics of aluminum
microparticles are investigated through precise single particle collisions with
two distinctive substrates, sapphire and aluminum, across a broad range of
collision velocities, from 50 to 1,100 m/s. An empirical constitutive model is
calibrated based on the experimental results, and is used to investigate the
mechanics of particle deformation history. Real-time and post-impact
characterizations, as well as model based simulations, show that significant
material flow occurs during the impact, especially with the sapphire substrate. A
material instability stemming from plasticity-induced heating is identified. The
presented methodology, based on the use of controlled single particle impact data
and constitutive models, provides an innovative approach for the prediction of
extreme material behavior.
PMID- 28698545
TI - A novel protein kinase inhibitor IMB-YH-8 with anti-tuberculosis activity.
AB - Protein kinase B (PknB) is one of the Mycobacterium tuberculosis serine/threonine
protein kinases and has an essential role in sustaining mycobacterial growth.
Here, we identified and characterized a novel small molecule compound named IMB
YH-8 that inhibited PknB and served as anti-mycobacteria lead compound. IMB-YH-8
inhibited PknB auto-phosphorylation and the phosphorylation of GarA by PknB in a
dose-dependent manner. The compound did not inhibit human Akt1 or other
serine/threonine kinases in M. tuberculosis except for the highly homologous
PknA. IMB-YH-8 bound to PknB with a moderate affinity. Molecular docking revealed
that IMB-YH-8 interacts with the catalytic domain of PknB. Observations of
electron microscopy showed that IMB-YH-8 changed the morphology of H37Rv and
disrupted the cell wall. The differential transcriptional response of M.
tuberculosis to IMB-YH-8 revealed changes in SigH regulatory pathways modulated
by PknB. Notably IMB-YH-8 not only potently inhibited drug-sensitive and
multidrug-resistant clinical isolates but also exhibited a dose dependent
inhibition of intracellular M. tuberculosis. Taken together, these in vitro data
demonstrate that IMB-YH-8 is a novel inhibitor of PknB, which potently prevents
growth of M. tuberculosis. It is as yet unclear whether inhibition of PknA
contributes to the anti-tubercular action of IMB-YH-8.
PMID- 28698546
TI - Obesity-induces Organ and Tissue Specific Tight Junction Restructuring and
Barrier Deregulation by Claudin Switching.
AB - Obesity increases susceptibility to multiple organ disorders, however, underlying
mechanisms remain unclear. The subclinical inflammation assisted by obesity
induced gut permeability may underlie obesity-associated co-morbidities. Despite
eminent clinical significance of the obesity led gut barrier abnormalities, its
precise molecular regulation remains unclear. It is also unknown whether barrier
deregulations, similar to the gut, characterize other vital organs in obese
individuals. The claudin family of proteins is integral to the tight junction
(TJ), the apical cell-cell adhesion and a key regulator of the epithelial
barrier. Using comprehensive physiological and biochemical analysis of intestinal
and renal tissues from high-fat diet fed mice, critical for maintaining metabolic
homeostasis, this study demonstrates that profound TJ-restructuring by organ and
tissue-specific claudin switching characterize obese organs. Protein expression
and cellular distribution were examined. In-silico analysis further highlighted
potential association of select claudins, modulated by the obesity, with
signaling and metabolic pathways of pathological significance. In vitro studies
using Leptin or DCA-treatment suggested causal significance of obesity-induced
changes in tissue microenvironment in regulating barrier deregulations in tissue
specific manner. Overall, current findings advances our understanding of the
molecular undertakings of obesity associated changes that help predispose to
specific diseases and also identifies novel windows of preventive and/or
therapeutic interventions.
PMID- 28698548
TI - A Five-Region Hypothesis Test for Exposure-Disease Associations.
AB - Characterizing exposure-disease associations is a central issue in epidemiology,
one which epidemiologists often approach by adopting the index of the odds ratio
and presenting its point estimate, p-value and confidence interval. In this
study, the parameter space of the odds ratio is partitioned into five mutually
exclusive regions corresponding to 'strong protective factor', 'weak protective
factor', 'no association', 'weak risk factor', and 'strong risk factor',
respectively. The authors presented a suite of statistical methods tailored to
such a five-region demarcation, including methods for hypothesis testing,
confidence interval estimation and calculation of the sample size needed to
obtain the desired level of statistical power. The authors show that the five
region methods can efficiently and informatively describe a putative exposure
disease association, including its presence or absence, as well as its direction
and strength (if any association exists). Three published results were re
analyzed to demonstrate the methods. R code is provided for convenience as well.
The five-region methods are recommended for routine use during the analysis of
epidemiologic data.
PMID- 28698547
TI - Metabolic reprogramming is associated with flavopiridol resistance in prostate
cancer DU145 cells.
AB - Flavopiridol (FP) is a pan-cyclin dependent kinase inhibitor, which shows strong
efficacy in inducing cancer cell apoptosis. Although FP is potent against most
cancer cells in vitro, unfortunately it proved less efficacious in clinical
trials in various aggressive cancers. To date, the molecular mechanisms of the FP
resistance are mostly unknown. Here, we report that a small fraction human
prostate cancer DU145 cells can survive long-term FP treatment and emerge as FP
resistant cells (DU145FP). These DU145FP cells show accumulated mitochondrial
lesions with stronger glycolytic features, and they proliferate in slow-cycling
and behave highly migratory with strong anti-apoptotic potential. In addition,
the cells are less sensitive to cisplatin and docetaxel-induced apoptotic
pressure, and over-express multiple stem cell associated biomarkers. Our studies
collectively uncover for the first time that FP-resistant prostate cancer cells
show metabolic remodeling, and the metabolic plasticity might be required for the
FP resistance-associated cancer cell stemness up-regulation.
PMID- 28698549
TI - A Tissue Engineered Model of Aging: Interdependence and Cooperative Effects in
Failing Tissues.
AB - Aging remains a fundamental open problem in modern biology. Although there exist
a number of theories on aging on the cellular scale, nearly nothing is known
about how microscopic failures cascade to macroscopic failures of tissues, organs
and ultimately the organism. The goal of this work is to bridge microscopic cell
failure to macroscopic manifestations of aging. We use tissue engineered
constructs to control the cellular-level damage and cell-cell distance in
individual tissues to establish the role of complex interdependence and
interactions between cells in aging tissues. We found that while microscopic
mechanisms drive aging, the interdependency between cells plays a major role in
tissue death, providing evidence on how cellular aging is connected to its higher
systemic consequences.
PMID- 28698550
TI - The PSMP-CCR2 interactions trigger monocyte/macrophage-dependent colitis.
AB - Monocytes/macrophages have been found to be an important component of colitis.
However, the key chemokine that initiates the CCR2+ monocytes migration from
circulation to colitis tissue remains to be undiscovered. PC3-secreted
microprotein (PSMP) is a novel chemokine whose receptor is CCR2. The
physiological and pathological functions of PSMP have not yet been reported. In
this study, PSMP was found to be expressed in colitis and colonic tumor tissues
from patients and significantly up-regulated in mouse DSS-induced colitis
tissues. PSMP overexpression in the colon aggravated the DSS-induced colitis and
the anti-PSMP neutralizing antibody mollified the colitis by reducing macrophage
infiltration and inhibiting the expression of IL-6, TNF-alpha and CCL2.
Furthermore, we demonstrated that lipopolysaccharide and muramyl dipeptide
induced PSMP expression in the colonic epithelial cells. PSMP was up-regulated in
the initial stage prior to IL-6, TNF-alpha and CCL2 up-regulated expression in
DSS colitis and promoted the M1 macrophages to produce CCL2. PSMP chemo-attracted
Ly6Chi monocytes in a CCR2 dependent manner via in situ chemotaxis and adoptive
transfer assays. Our data identify PSMP as a key molecule in ulcerative colitis,
which provides a novel mechanism of monocyte/macrophage migration that affects
gut innate immunity and makes PSMP a potential target for controlling colitis.
PMID- 28698551
TI - Laminin-511 and -521-based matrices for efficient ex vivo-expansion of human
limbal epithelial progenitor cells.
AB - Optimization of culture conditions for human limbal epithelial stem/progenitor
cells (LEPC) that incorporate the in vivo cell-matrix interactions are essential
to enhance LEPC ex vivo-expansion and transplantation efficiency. Here, we
investigate the efficacy of laminin (LN) isoforms preferentially expressed in the
limbal niche as culture matrices for epithelial tissue engineering. Analyses of
expression patterns of LN chains in the human limbal niche provided evidence for
enrichment of LN-alpha2, -alpha3, -alpha5, -beta1, -beta2, -beta3, -gamma1,
gamma2 and -gamma3 chains in the limbal basement membrane, with LN-alpha5
representing a signature component specifically produced by epithelial progenitor
cells. Recombinant human LN-521 and LN-511 significantly enhanced in vitro LEPC
adhesion, migration and proliferation compared to other isoforms, and maintained
phenotype stability. The bioactive LN-511-E8 fragment carrying only C-terminal
domains showed similar efficacy as full-length LN-511. Functional blocking of
alpha3beta1 and alpha6beta1 integrins suppressed adhesion of LEPC to LN-511/521
coated surfaces. Cultivation of LEPC on fibrin-based hydrogels incorporating LN
511-E8 resulted in firm integrin-mediated adhesion to the scaffold and well
stratified epithelial constructs, with maintenance of a progenitor cell phenotype
in their (supra)basal layers. Thus, the incorporation of chemically defined LN
511-E8 into biosynthetic scaffolds represents a promising approach for xeno-free
corneal epithelial tissue engineering for ocular surface reconstruction.
PMID- 28698552
TI - SmMYB36, a Novel R2R3-MYB Transcription Factor, Enhances Tanshinone Accumulation
and Decreases Phenolic Acid Content in Salvia miltiorrhiza Hairy Roots.
AB - Phenolic acids and tanshinones are two major bioactive components in Salvia
miltiorrhiza Bunge. A novel endogenous R2R3-MYB transcription factor, SmMYB36,
was identified in this research. This transcript factor can simultaneously
influence the content of two types of components in SmMYB36 overexpression hairy
roots. SmMYB36 was mainly localized in the nucleus of onion epidermis and it has
transactivation activity. The overexpression of SmMYB36 promoted tanshinone
accumulation but inhibited phenolic acid and flavonoid biosynthesis in Salvia
miltiorrhiza hairy roots. The altered metabolite content was due to changed
metabolic flow which was regulated by transcript expression of metabolic pathway
genes. The gene transcription levels of the phenylpropanoid general pathway,
tyrosine derived pathway, methylerythritol phosphate pathway and downstream
tanshinone biosynthetic pathway changed significantly due to the overexpression
of SmMYB36. The wide distribution of MYB binding elements (MBS, MRE, MBSI and
MBSII) and electrophoretic mobility shift assay results indicated that SmMYB36
may be an effective tool to regulate metabolic flux shifts.
PMID- 28698553
TI - Efficient Characterization and Classification of Contrast Sensitivity Functions
in Aging.
AB - The contrast sensitivity function (CSF), delineating contrast sensitivity over a
wide range of spatial frequencies, provides a comprehensive characterization of
spatial vision and a sensitive test for many physiological and pathological
processes. A precise CSF measurement tool for the aging population is of great
theoretical and practical importance. In the current study, we tested whether the
assumptions of the newly developed quick CSF method were valid and whether it can
rapidly, reliably, and effectively evaluate CSFs in the aging population. The
quick CSF method combines Bayesian adaptive inference with an information gain
strategy to directly estimate four parameters that define the observer's CSF.
Eighteen young and twenty-five old observers participated in the evaluation of
the quick CSF method. All observers were screened for ophthalmological and mental
diseases. Our results showed that the CSFs derived from the quick CSF method well
matched with those from the traditional Psi method, with excellent test-retest
reliability. More importantly, the quick CSF method can accurately detect the
difference of CSFs between the young and old groups. Aging significantly degrades
contrast sensitivity. The quick CSF method demonstrates great potentials for both
laboratory research and clinical applications in the aging population.
PMID- 28698554
TI - Chondroprotection by urocortin involves blockade of the mechanosensitive ion
channel Piezo1.
AB - Osteoarthritis (OA) is characterised by progressive destruction of articular
cartilage and chondrocyte cell death. Here, we show the expression of the
endogenous peptide urocortin1 (Ucn1) and two receptor subtypes, CRF-R1 and CRF
R2, in primary human articular chondrocytes (AC) and demonstrate its role as an
autocrine/paracrine pro-survival factor. This effect could only be removed using
the CRF-R1 selective antagonist CP-154526, suggesting Ucn1 acts through CRF-R1
when promoting chondrocyte survival. This cell death was characterised by an
increase in p53 expression, and cleavage of caspase 9 and 3. Antagonism of CRF-R1
with CP-154526 caused an accumulation of intracellular calcium (Ca2+) over time
and cell death. These effects could be prevented with the non-selective cation
channel blocker Gadolinium (Gd3+). Therefore, opening of a non-selective cation
channel causes cell death and Ucn1 maintains this channel in a closed
conformation. This channel was identified to be the mechanosensitive channel
Piezo1. We go on to determine that this channel inhibition by Ucn1 is mediated
initially by an increase in cyclic adenosine monophosphate (cAMP) and a
subsequent inactivation of phospholipase A2 (PLA2), whose metabolites are known
to modulate ion channels. Knowledge of these novel pathways may present
opportunities for interventions that could abrogate the progression of OA.
PMID- 28698555
TI - Association between duration of breastfeeding and malocclusions in primary and
mixed dentition: a systematic review and meta-analysis.
AB - The aim of this systematic review and meta-analysis was to examine the current
evidence on the possible effects of breastfeeding on different malocclusion
traits in primary and mixed dentition. A systematic search was made in three
databases, using terms related to breastfeeding and malocclusion in primary and
mixed dentition. Of the 31 articles that met the inclusion criteria and were
included in the qualitative analysis, nine were included in the quantitative
analysis. The quality of the 31 observational studies was moderate to high on the
Newcastle-Ottawa Scale. It was found that the odds ratio for the risk of
posterior crossbite was 3.76 (95% CI 2.01-7.03) on comparing children who had not
been breastfed, with those breastfed for over six months, and rose to 8.78 (95%
CI 1.67-46.1) when those not breastfed were compared to those breastfed for over
twelve months. The odds ratio for class II malocclusion in children breastfed for
up to six months compared to those breastfed for over six months was 1.25 (95% CI
1.01-1.55). Lastly, children who were breastfed for up to six months had an odds
ratio of 1.73 (95% CI 1.35-2.22) for non-spaced dentition compared to those who
were breastfed for over six months.
PMID- 28698556
TI - Location Sensitive Deep Convolutional Neural Networks for Segmentation of White
Matter Hyperintensities.
AB - The anatomical location of imaging features is of crucial importance for accurate
diagnosis in many medical tasks. Convolutional neural networks (CNN) have had
huge successes in computer vision, but they lack the natural ability to
incorporate the anatomical location in their decision making process, hindering
success in some medical image analysis tasks. In this paper, to integrate the
anatomical location information into the network, we propose several deep CNN
architectures that consider multi-scale patches or take explicit location
features while training. We apply and compare the proposed architectures for
segmentation of white matter hyperintensities in brain MR images on a large
dataset. As a result, we observe that the CNNs that incorporate location
information substantially outperform a conventional segmentation method with
handcrafted features as well as CNNs that do not integrate location information.
On a test set of 50 scans, the best configuration of our networks obtained a Dice
score of 0.792, compared to 0.805 for an independent human observer. Performance
levels of the machine and the independent human observer were not statistically
significantly different (p-value = 0.06).
PMID- 28698557
TI - Controls on eDNA movement in streams: Transport, Retention, and Resuspension.
AB - Advances in detection of genetic material from species in aquatic ecosystems,
including environmental DNA (eDNA), have improved species monitoring and
management. eDNA from target species can readily move in streams and rivers and
the goal is to measure it, and with that infer where and how abundant species
are, adding great value to delimiting species invasions, monitoring and
protecting rare species, and estimating biodiversity. To date, we lack an
integrated framework that identifies environmental factors that control eDNA
movement in realistic, complex, and heterogeneous flowing waters. To this end,
using an empirical approach and a simple conceptual model, we propose a framework
of how eDNA is transported, retained, and resuspended in stream systems. Such an
understanding of eDNA dispersal in streams will be essential for designing
optimized sampling protocols and subsequently estimating biomass or organismal
abundance. We also discuss guiding principles for more effective use of eDNA
methods, highlighting the necessity of understanding these parameters for use in
future predictive modeling of eDNA transport.
PMID- 28698558
TI - Effects of water level regulation on the seed germination and production of
annual plant Xanthium sibiricum in the water-level-fluctuating-zone of Three
Gorges Reservoir.
AB - Vegetation effectively slows down the deterioration rate of the ecosystem in the
water-level fluctuation zone (WLFZ). In this study, we investigated the impact of
impoundment on the germination of seeds from Xanthium sibiricum fruits with
various degrees of maturity and produced by X. sibiricum plants growing at
different elevations in the WLFZ. Seed production by X. sibiricum under the
current water level regulation mode was also investigated. Seeds were collected
from seven elevations of the WLFZ of Three Gorges Reservoir (TGR) and exposed at
these elevations to submergence. Seed production of the plants germinated from X.
sibiricum seeds was observed. The maturity degree of X. sibiricum fruits from
different elevations has no influence on the seed production by the plants that
are produced from the fruits. Under the present water-level regulation mode, X.
sibiricum growing above 155 m are able to generate mature seeds and thus provide
seed sources for population maintenance, although the plants growing at an
elevation below 165 m failed to produce fruits in 2010 due to unusual flooding.
This study is useful for the vegetation recovery and reconstruction in other
regions with hydrological characteristics similar to that of the TGR.
PMID- 28698559
TI - Repression of Abd-B by Polycomb is critical for cell identity maintenance in
adult Drosophila testis.
AB - Hox genes play a fundamental role in regulating animal development. However, less
is known about their functions on homeostasis maintenance in adult stem cells.
Here, we report that the repression of an important axial Hox gene, Abdominal-B
(Abd-B), in cyst stem cells (CySCs) is essential for the homeostasis and cell
identity maintenance in the adult Drosophila testis. Derepression of Abd-B in
CySCs disrupts the proper self-renewal of both germline stem cells (GSCs) and
CySCs, and leads to an excessive expansion of early stage somatic cells, which
originate from both lineages. We further demonstrate that canonical Polycomb (Pc)
and functional pathway of Polycomb group (PcG) proteins are responsible for
maintaining the germline cell identity non-autonomously via repressing Abd-B in
CySCs in the adult Drosophila testis.
PMID- 28698560
TI - All muscarinic acetylcholine receptors (M1-M5) are expressed in murine brain
microvascular endothelium.
AB - Clinical and experimental studies indicate that muscarinic acetylcholine
receptors are potential pharmacological targets for the treatment of neurological
diseases. Although these receptors have been described in human, bovine and rat
cerebral microvascular tissue, a subtype functional characterization in mouse
brain endothelium is lacking. Here, we show that all muscarinic acetylcholine
receptors (M1-M5) are expressed in mouse brain microvascular endothelial cells.
The mRNA expression of M2, M3, and M5 correlates with their respective protein
abundance, but a mismatch exists for M1 and M4 mRNA versus protein levels.
Acetylcholine activates calcium transients in brain endothelium via muscarinic,
but not nicotinic, receptors. Moreover, although M1 and M3 are the most abundant
receptors, only a small fraction of M1 is present in the plasma membrane and
functions in ACh-induced Ca2+ signaling. Bioinformatic analyses performed on
eukaryotic muscarinic receptors demonstrate a high degree of conservation of the
orthosteric binding site and a great variability of the allosteric site. In line
with previous studies, this result indicates muscarinic acetylcholine receptors
as potential pharmacological targets in future translational studies. We argue
that research on drug development should especially focus on the allosteric
binding sites of the M1 and M3 receptors.
PMID- 28698561
TI - A combined case-control and molecular source attribution study of human
Campylobacter infections in Germany, 2011-2014.
AB - Campylobacter infection is the most commonly notified bacterial enteritis in
Germany. We performed a large combined case-control and source attribution study
(Nov 2011-Feb 2014) to identify risk factors for sporadic intestinal
Campylobacter infections and to determine the relative importance of various
animal sources for human infections in Germany. We conducted multivariable
logistic regression analysis to identify risk factors. Source attribution
analysis was performed using the asymmetric island model based on MLST data of
human and animal/food isolates. As animal sources we considered chicken, pig, pet
dog or cat, cattle, and poultry other than chicken. Consumption of chicken meat
and eating out were the most important risk factors for Campylobacter infections.
Additional risk factors were preparation of poultry meat in the household;
preparation of uncooked food and raw meat at the same time; contact with poultry
animals; and the use of gastric acid inhibitors. The mean probability of human C.
jejuni isolates to originate from chickens was highest (74%), whereas pigs were a
negligible source for C. jejuni infections. Human C. coli isolates were likely to
originate from chickens (56%) or from pigs (32%). Efforts need to be intensified
along the food chain to reduce Campylobacter load, especially on chicken meat.
PMID- 28698562
TI - C-terminal deletion of NOTCH1 intracellular domain (N1ICD) increases its
stability but does not amplify and recapitulate N1ICD-dependent signalling.
AB - Since the generation of a mouse strain conditionally expressing the active
intracellular domain of Notch1 (N1ICD), many laboratories have exploited this
model (RosaN1-ICD) to assess the impact of constitutive Notch1 signalling
activation in normal and pathological processes. It should be underscored that
Cre-recombination leads to the expression of a C-terminally truncated form of
N1ICD (N1ICDdC) in the RosaN1-ICD mutant mice. Given that no studies were
undertaken to delineate whether deletion of this region leaves intact N1ICD
function, stable cell lines with single targeted integration of inducible N1ICD
and N1ICDdC were generated. We found that C-terminal deletion of N1ICD stabilized
the protein but did not promote the activity of Notch responsive promoters.
Furthermore, despite higher expression levels, N1ICDdC failed to phenocopy N1ICD
in the promotion of anchorage-independent growth. Our results thus suggest that
the C-terminal region of N1ICD plays a role in shaping the Notch response.
Therefore, it should be taken into consideration that N1ICD is truncated when
interpreting phenotypes of RosaN1-ICD mutant mice.
PMID- 28698563
TI - Thermometry of bosonic mixtures in Optical Lattices via Demixing.
AB - Motivated by recent experiments and theoretical investigations on binary
mixtures, we investigate the miscible-immiscible transition at finite temperature
by means of Quantum Monte Carlo. Based on the observation that the segregated
phase is strongly affected by temperature, we propose to use the degree of
demixing for thermometry of a binary bosonic mixture trapped in an optical
lattice. We show that the proposed method is especially sensitive at low
temperatures, of the order of the tunnelling amplitude, and therefore is
particularly suitable in the regime where quantum magnetism is expected.
PMID- 28698564
TI - Homer binds to Orai1 and TRPC channels in the neointima and regulates vascular
smooth muscle cell migration and proliferation.
AB - The molecular components of store-operated Ca2+ influx channels (SOCs) in
proliferative and migratory vascular smooth muscle cells (VSMCs) are quite
intricate with many channels contributing to SOCs. They include the Ca2+
selective Orai1 and members of the transient receptor potential canonical (TRPC)
channels, which are activated by the endoplasmic reticulum Ca2+ sensor STIM1. The
scaffolding protein Homer assembles SOC complexes, but its role in VSMCs is not
well understood. Here, we asked whether these SOC components and Homer1 are
present in the same complex in VSMCs and how Homer1 contributes to VSMC SOCs,
proliferation, and migration leading to neointima formation. Homer1 expression
levels are upregulated in balloon-injured vs. uninjured VSMCs.
Coimmunoprecipitation assays revealed the presence and interaction of all SOC
components in the injured VSMCs, where Homer1 interacts with Orai1 and various
TRPC channels. Accordingly, knockdown of Homer1 in cultured VSMCs partially
inhibited SOCs, VSMC migration, and VSMC proliferation. Neointimal area was
reduced after treatment with an adeno-associated viral vector expressing a short
hairpin RNA against Homer1 mRNA (AAV-shHomer1). These findings stress the role of
multiple Ca2+ influx channels in VSMCs and are the first to show the role of
Homer proteins in VSMCs and its importance in neointima formation.
PMID- 28698565
TI - Integrating nonstationary behaviors of typhoon and non-typhoon extreme rainfall
events in East Asia.
AB - Extreme rainfall events in East Asia can be derived from the two subcomponents of
tropical cyclones (TC) and non-TC based rainfall (mostly summer monsoons).
Critical natural hazards including floods and landslides occur repeatedly due to
the heavy rainfall associated with the two subcomponents, and disaster losses are
increasing because global warming has caused changes in the extreme rainfall
characteristics of two subcomponents. Subsequently, the frequency and intensity
of extreme rainfall have reportedly become nonstationary. The majority of
literature on nonstationary frequency analyses do not account for the different
behaviors (stationarity or nonstationarity) of annual maximum rainfall (AMR) from
the two subcomponents (PM TC and PM NTC ). To carry out a nonstationary frequency
analysis considering the different behaviors of the PM TC and PM NTC series, this
study proposes a novel approach of integrating the fitted PM TC and PM NTC series
after modeling the nonstationarity of the PM TC and PM NTC series individually.
The presented results conclude that the proposed approach provides more reliable
estimates than existing nonstationary approaches by reflecting the different
features of the PM TC and PM NTC series. We suggest that the proposed approach
provides a reasonable design rainfall in constructing hydraulics to mitigate the
different nonstationary effects of two TC and non-TC rainfall extremes.
PMID- 28698566
TI - Evaluation of Osteogenesis and Angiogenesis of Icariin in Local Controlled
Release and Systemic Delivery for Calvarial Defect in Ovariectomized Rats.
AB - Typically, bone regenerative medicine is applied to repair bone defects in
patients with osteoporosis. Meanwhile, there is an urgent need to develop safe
and cheap drugs that induce bone formation. Icariin, which is reported to promote
the osteogenesis of stem cells in vitro, is the main active component of Herba
Epimedii. However, whether icariin could repair bone defects caused by
osteoporosis remains unknown. In this study, an osteoporosis model in rats was
established by an ovariectomy first, and then, the osteogenic and angiogenic
differentiation of bone mesenchymal stem cells (BMSCs) treated with icariin was
evaluated. Furthermore, calcium phosphate cement (CPC) scaffolds loaded with
icariin were constructed and then implanted into nude mice to determine the
optimal construction. To evaluate its osteogenic and angiogenic ability in vivo,
this construction was applied to calvarial defect of the ovariectomized (OVX)
rats accompanied with an icariin gavage. This demonstrated that icariin could up
regulate the expression of osteogenic and angiogenic genes in BMSCs. Meanwhile,
osteoclast formation was inhibited. Moreover, CPC could act as a suitable icariin
delivery system for repairing bone defects by enhancing osteogenesis and
angiogenesis, while the systemic administration of icariin has an
antiosteoporotic effect that promotes bone defect repair.
PMID- 28698567
TI - Advanced redox flow fuel cell using ferric chloride as main catalyst for complete
conversion from carbohydrates to electricity.
AB - Liquid catalyzed fuel cell (LCFC) is a kind of redox flow fuel cell directly
converting carbohydrates to electricity. To improve its efficiency, ferric
chloride (FeCl3) was introduced as main catalyst. As mono catalyst,
phosphomolybdic acid (PMo12) was much better than phosphotungstic acid (PW12) and
FeCl3 was intermediate between them. Compared with PMo12 at the optimal dose of
0.30 mol/L, the combination of FeCl3 (1.00 mol/L) and PW12 (0.06 mol/L) achieved
similar power output from glucose (2.59 mW/cm2) or starch (1.57 mW/cm2), and even
improved the maximum power density by 57% from 0.46 to 0.72 mW/cm2 when using
cellulose as the fuel. Long-term continuous operation of the LCFC indicated that
carbohydrates can be hydrolyzed to glucose and then oxidized stepwise to carbon
dioxide. At the latter stage, there was a linear relationship between the
electron transfer number from glucose to catalyst and the subsequent cell
performance. Based on these findings, the contribution of FeCl3 to LCFC should be
derived from the accelerated hydrolysis and oxidation of carbohydrates and the
enhanced electron transfer from glucose to anode. The addition of FeCl3 reduced
the usage of polyoxometalates by 80%, and the replacement implied that LCFC can
be operated less toxically and more economically.
PMID- 28698568
TI - An allelic variant of the PmrB sensor kinase responsible for colistin resistance
in an Escherichia coli strain of clinical origin.
AB - We investigated the colistin resistance mechanism in an Escherichia coli strain
(LC711/14) isolated in Italy in 2014, from an urinary tract infection, which was
previously shown to express a colistin resistance mechanism different from mcr-1.
LC711/14 was found to carry a novel mutation in the pmrB gene, resulting in a
leucine to proline amino acid substitution at position 10 of the PmrB sensor
kinase component of the PmrAB signal transduction system. The role of this
substitution in colistin resistance was documented by expression of the wild-type
and mutated alleles in a pmrB deletion derivative of the E. coli reference strain
MG1655, in which expression of the mutated allele conferred colistin resistance
and upregulation of the endogenous pmrHFIJKLM lipid A modification system.
Complementation of LC711/14 with the wild-type pmrB allele restored colistin
susceptibility and decreased expression of pmrHFIJKLM, confirming the role of
this PmrB mutation. Substitution of leucine at position 10 of PmrB with other
amino acids (glycine and glutamine) resulted in loss of function, underscoring a
key role of this residue which is located in the cytoplasmic secretion domain of
the protein. This work demonstrated that mutation in this domain of the PmrB
sensor kinase can be responsible for acquired colistin resistance in E. coli
strains of clinical origin.
PMID- 28698569
TI - AhpC of the mycobacterial antioxidant defense system and its interaction with its
reducing partner Thioredoxin-C.
AB - Despite the highly oxidative environment of the phagosomal lumen, the need for
maintaining redox homeostasis is a critical aspect of mycobacterial biology. The
pathogens are equipped with the sophisticated thioredoxin- (Trx) and
peroxiredoxin system, including TrxC and the alkyl hydroperoxide reductase
subunit C (AhpC), whereby TrxC is one of the reducing partners of AhpC. Here we
visualize the redox modulated dodecamer ring formation of AhpC from Mycobacterium
bovis (BCG strain; MbAhpC) using electron microscopy and present novel insights
into the unique N-terminal epitope (40 residues) of mycobacterial AhpC.
Truncations and amino acid substitutions of residues in the unique N-terminus of
MbAhpC provide insights into their structural and enzymatic roles, and into the
evolutionary divergence of mycobacterial AhpC versus that of other bacteria.
These structural details shed light on the epitopes and residues of TrxC which
contributes to its interaction with AhpC. Since human cells lack AhpC, the unique
N-terminal epitope of mycobacterial AhpC as well as the MbAhpC-TrxC interface
represent an ideal drug target.
PMID- 28698570
TI - Exo70 is an independent prognostic factor in colon cancer.
AB - Exo70, a key component of the Exocyst complex, plays important roles in human
cancer progression beyond exocytosis. However, the expression of Exo70 and its
prognostic value for patients with colon cancer has not been well investigated to
date. In this study, we observed that the mRNA and protein levels of Exo70 were
upregulated in 11 of 13 colon cancer tissues, compared with their normal
counterparts, which was validated by immunohistochemical analysis in a tissue
microarray containing 89 pairs of colon cancer tissues and the matched adjacent
normal tissues. Statistical analysis revealed that Exo70 expression is positively
correlated with tumor size, invasion depth, TNM stage and distant metastasis.
Kaplan-Meier survival analysis showed that colon cancer patients with higher
Exo70 expression have a poorer clinical outcome than those with lower Exo70
expression. Multivariate Cox regression analysis revealed that Exo70, age and
distant metastasis were there independent prognostic factors for overall survival
rate of colon cancer patients. Through gain- and loss of Exo70 in colon cancer
cells, we found that Exo70 could enhance the migration ability of colon cancer
cells. Taken together, our studies revealed that Exo70 might be a promising
negative prognostic factor and a potential therapeutic target for colon cancer.
PMID- 28698571
TI - Injectable hybrid system for strontium local delivery promotes bone regeneration
in a rat critical-sized defect model.
AB - Strontium (Sr) has been described as having beneficial influence in bone strength
and architecture. However, negative systemic effects have been reported on oral
administration of Sr ranelate, leading to strict restrictions in clinical
application. We hypothesized that local delivery of Sr improves osteogenesis
without eliciting detrimental side effects. Therefore, the in vivo response to an
injectable Sr-hybrid system composed of RGD-alginate hydrogel cross-linked in
situ with Sr and reinforced with Sr-doped hydroxyapatite microspheres, was
investigated. The system was injected in a critical-sized bone defect model and
compared to a similar Sr-free material. Micro-CT results show a trend towards
higher new bone formed in Sr-hybrid group and major histological differences were
observed between groups. Higher cell invasion was detected at the center of the
defect of Sr-hybrid group after 15 days with earlier bone formation. Higher
material degradation with increase of collagen fibers and bone formation in the
center of the defect after 60 days was observed as opposed to bone formation
restricted to the periphery of the defect in the control. These histological
findings support the evidence of an improved response with the Sr enriched
material. Importantly, no alterations were observed in the Sr levels in systemic
organs or serum.
PMID- 28698572
TI - The effect of calorie restriction on mouse skeletal muscle is sex, strain and
time-dependent.
AB - Loss of skeletal muscle mass and function occurs with increasing age. Calorie
restriction (CR) increases the lifespan of C57Bl/6 mice, but not in the shorter
lived DBA/2 strain. There is some evidence that calorie restriction reduces or
delays many of the age-related defects that occur in rodent skeletal muscle. We
therefore investigated the effect of short (2.5 month) and longer term (8.5 and
18.5 months) CR on skeletal muscle in male and female C57Bl/6 and DBA/2 mice. We
found that short-term CR increased the satellite cell number and collagen VI
content of muscle, but resulted in a delayed regenerative response to
injury.Consistent with this, the in vitro proliferation of satellite cells
derived from these muscles was reduced by CR. The percentage of stromal cells,
macrophages, hematopoietic stem cells and fibroadipogenic cells in the
mononucleated cell population derived from skeletal muscle was reduced by CR at
various stages. But overall, these changes are neither consistent over time, nor
between strain and sex. The fact that changes induced by CR do not persist with
time and the dissimilarities between the two mouse strains, combined with sex
differences, urge caution in applying CR to improve skeletal muscle function
across the lifespan in humans.
PMID- 28698573
TI - Tropic origins, a dispersal model for saprotrophic mushrooms in Agaricus section
Minores with descriptions of sixteen new species.
AB - Agaricus section Minores contains the richest species diversity within the genus.
Its Phylogeny is firstly presented by a Maximum Likelihood tree generated through
DNA sequences from four gene regions of 91 species. Furthermore, a molecular
dating analysis is conducted used those sequences, and it provided the divergence
times of the clades within section Minores. Study showed section Minores has a
tropical origin. Four main dispersal routes are proposed: (1) species from South
Asia migrated through the Tibetan Plateau and reached Europe ca. 9-13 Ma; (2)
species from out of South Asia dispersed to Europe in the earlier time of ca. 22
Ma; (3) species from South Asia dispersed through North Asia to Alaska, and
reached West America around ca. 9 Ma; and (4) species from South Asia dispersed
south and reached Oceania by at least three invading events about ca. 9, 12 and
16-18 Ma respectively. Those routes excepting the second route coincide with
those of ectomycorrhizal mushrooms. To know whether the second route existed in
the saprotrophic mushrooms requires further studies, and the fourth route may
explain why the secotioid species occurring in Australia are morphologically
similar but cluster in different phylogenetic clades. This study also
demonstrates a great biodiversity of A. section Minores in China. Sixteen new
species and three new records are introduced from China with morphological
descriptions, illustrations, color photographs and phylogenetic analyses.
PMID- 28698574
TI - An E2F1/MiR-17-92 Negative Feedback Loop mediates proliferation of Mouse Palatal
Mesenchymal Cells.
AB - Normal cell cycle progression and proliferation of palatal mesenchymal cells are
important for palatal development. As targets of miR-17-92, E2F transcription
factors family has been suggested to induce the transcription of miR-17-92 in
several cell types. In the present study, we sought to investigate whether this
negative feedback loop exists in mouse PMCs and what the function of this
negative feedback loop would be in palatal mesenchymal cells. Using GeneMANIA, we
revealed that the most important function of experimentally verified targets of
miR-17-92 is cell cycle regulation. E2F1 and E2F3, but not E2F2, were extensively
expressed in mouse palate. Over-expression of E2F1 significantly increased the
expression of all the members of miR-17-92. After increased by E2F1, miR-17 and
miR-20a may negatively target E2F1, and thereby prevent the cells from excessive
proliferation. We suggest that the negative feedback loop between E2F1 and miR-17
92 may contribute to palatal development by regulating the proliferation and cell
cycle of palatal mesenchymal cells.
PMID- 28698575
TI - Dual non-contiguous peptide occupancy of HLA class I evoke antiviral human CD8 T
cell response and form neo-epitopes with self-antigens.
AB - Host CD8 T cell response to viral infections involves recognition of 8-10-mer
peptides presented by MHC-I molecules. However, proteasomes generate
predominantly 2-7-mer peptides, but the role of these peptides is largely
unknown. Here, we show that single short peptides of <8-mer from Latent Membrane
Protein 2 (LMP2) of Epstein Barr Virus (EBV) can bind HLA-A*11:01 and stimulate
CD8+ cells. Surprisingly, two peptide fragments between 4-7-mer derived from
LMP2(340-349) were able to complement each other, forming combination epitopes
that can stimulate specific CD8+ T cell responses. Moreover, peptides from self
antigens can complement non-self peptides within the HLA binding cleft, forming
neoepitopes. Solved structures of a tetra-complex comprising two peptides, HLA
and beta2-microglobulin revealed the free terminals of the two peptides to adopt
an upward conformation directed towards the T cell receptor. Our results
demonstrate a previously unknown mix-and-match combination of dual peptide
occupancy in HLA that can generate vast combinatorial complexity.
PMID- 28698576
TI - Multimodal imaging quality control of epithelia regenerated with cultured human
donor corneal limbal epithelial stem cells.
AB - Current imaging techniques for the characterization of differentiated corneal
limbal stem cells are destructive and cannot be used in eye bank for monitoring
the regenerated epithelium in culture. We presented a minimally invasive,
multimodal, marker-free imaging method for the investigation of epithelia
regenerated with cultured human donor corneal limbal epithelial stem cells. Two
photon fluorescence and harmonic generation signals were collected from specimens
in culture and used for evaluating the structure and morphology of epithelia
cultured on two different bio-scaffolds; in addition, donor human corneal tissues
were used as controls. The method provided reliable information on the
organization of cellular and extracellular components of biomaterial substrates
and was highly sensitive to determine differences between the density packing
arrangement of epithelial cells of different biomaterials without relying on
inferences from exogenous labels. The present minimally invasive standardized
quality control methodology can be reliably translated to eye banks and used for
monitoring harvested corneal limbal stem cells growth and differentiation in
bioengineered materials.
PMID- 28698577
TI - The evolutionary advantage of heritable phenotypic heterogeneity.
AB - Phenotypic plasticity is an evolutionary driving force in diverse biological
processes, including the adaptive immune system, the development of neoplasms,
and the persistence of pathogens despite drug pressure. It is essential,
therefore, to understand the evolutionary advantage of an allele that confers on
cells the ability to express a range of phenotypes. Here, we study the fate of a
new mutation that allows the expression of multiple phenotypic states, introduced
into a finite population of individuals that can express only a single phenotype.
We show that the advantage of such a mutation depends on the degree of phenotypic
heritability between generations, called phenotypic memory. We analyze the
fixation probability of the phenotypically plastic allele as a function of
phenotypic memory, the variance of expressible phenotypes, the rate of
environmental changes, and the population size. We find that the fate of a
phenotypically plastic allele depends fundamentally on the environmental regime.
In constant environments, plastic alleles are advantageous and their fixation
probability increases with the degree of phenotypic memory. In periodically
fluctuating environments, by contrast, there is an optimum phenotypic memory that
maximizes the probability of the plastic allele's fixation. This same optimum
memory also maximizes geometric mean fitness, in steady state. We interpret these
results in the context of previous studies in an infinite-population framework.
We also discuss the implications of our results for the design of therapies that
can overcome persistence and, indirectly, drug resistance.
PMID- 28698578
TI - Dopamine 2 Receptor Activation Entrains Circadian Clocks in Mouse Retinal Pigment
Epithelium.
AB - Many of the physiological, cellular, and molecular rhythms that are present
within the eye are under the control of circadian clocks. Experimental evidence
suggests that the retinal circadian clock, or its output signals (e.g., dopamine
and melatonin), may contribute to eye disease and pathology. We recently
developed a retinal pigment ephithelium (RPE)-choroid preparation to monitor the
circadian clock using PERIOD2 (PER2)::LUC knock-in mouse. In this study we report
that dopamine, but not melatonin, is responsible for entrainment of the PER2::LUC
bioluminescence rhythm in mouse RPE-choroid. Dopamine induced phase-advances of
the PER2::LUC bioluminescence rhythm during the subjective day and phase-delays
in the late subjective night. We found that dopamine acts exclusively through
Dopamine 2 Receptors to entrain the circadian rhythm in PER2::LUC
bioluminescence. Finallly, we found that DA-induced expression of core circadian
clock genes Period1 and Period2 accompanied both phase advances and phase delays
of the RPE-choroid clock, thus suggesting that - as in other tissues - the rapid
induction of these circadian clock genes drives the resetting process. Since the
RPE cells persist for the entire lifespan of an organism, we believe that RPE
choroid preparation may represent a new and unique tool to study the effects of
circadian disruption during aging.
PMID- 28698579
TI - Industrial water resources management based on violation risk analysis of the
total allowable target on wastewater discharge.
AB - To improve the capabilities of conventional methodologies in facilitating
industrial water allocation under uncertain conditions, an integrated approach
was developed through the combination of operational research, uncertainty
analysis, and violation risk analysis methods. The developed approach can (a)
address complexities of industrial water resources management (IWRM) systems, (b)
facilitate reflections of multiple uncertainties and risks of the system and
incorporate them into a general optimization framework, and (c) manage robust
actions for industrial productions in consideration of water supply capacity and
wastewater discharging control. The developed method was then demonstrated in a
water-stressed city (i.e., the City of Dalian), northeastern China. Three
scenarios were proposed according to the city's industrial plans. The results
indicated that in the planning year of 2020 (a) the production of civilian-used
steel ships and machine-made paper & paperboard would reduce significantly, (b)
violation risk of chemical oxygen demand (COD) discharge under scenario 1 would
be the most prominent, compared with those under scenarios 2 and 3,
PMID- 28698580
TI - The genetic architecture of water-soluble protein content and its genetic
relationship to total protein content in soybean.
AB - Water-soluble protein content (WSPC) is a critical factor in both soybean protein
quality and functionality. However, the underlying genetic determinants are
unclear. Here, we used 219 soybean accessions and 152 recombinant inbred lines
genotyped with high-density markers and phenotyped in multi-environments to
dissect the genetic architectures of WSPC and protein content (PC) using single-
and multi-locus genome-wide association studies. In the result, a total of 32
significant loci, including 10 novel loci, significantly associated with WSPC and
PC across multi-environments were identified, which were subsequently validated
by linkage mapping. Among these loci, only four exhibited pleiotropic effects for
PC and WSPC, explaining the low correlation coefficient between the two traits.
The largest-effect WSPC-specific loci, GqWSPC8, was stably identified across all
six environments and tagged to a linkage disequilibrium block comprising two
promising candidate genes AAP8 and 2 S albumin, which might contribute to the
high level of WSPC in some soybean varieties. In addition, two genes,
Glyma.13G123500 and Glyma.13G194400 with relatively high expression levels at
seed development stage compared with other tissues were regarded as promising
candidates associated with the PC and WSPC, respectively. Our results provide new
insights into the genetic basis of WSPC affecting soybean protein quality and
yield.
PMID- 28698581
TI - GTSE1 promotes cell migration and invasion by regulating EMT in hepatocellular
carcinoma and is associated with poor prognosis.
AB - G2 and S phase-expressed-1 (GTSE1) regulates G1/S cell cycle transition. It was
recently reported to be overexpressed in certain human cancers, but its
significance and mechanism(s) in hepatocellular carcinoma (HCC) remain unknown.
Here, we showed preferential GTSE1 upregulation in human HCC tissues and cell
lines that positively correlated with Ki67. GTSE1 knockdown by short hairpin RNA
resulted in deficient colony-forming ability and depleted capabilities of HCC
cells to migrate and invade. Conversely, exogenous GTSE1 overexpression enhanced
colony formation and stimulated HCC cell migration and invasion. Furthermore,
GTSE1 silencing was associated with the downregulation of N-cadherin, beta
catenin, and Snail, whereas GTSE1 overexpression caused the opposite effects.
GTSE1 upregulated Snail via both transcription and protein degradation pathways.
Additionally, GTSE1 modulated the sensitivity of HCC to 5-fluorouracil therapy.
High GTSE1 correlates with chemo-resistance, while low GTSE1 increases drug
sensitivity. Kaplan-Meier survival analysis indicated that high GTSE1 levels were
significantly associated with poor overall survival. In conclusion, high
expression of GTSE1 is commonly noted in HCC and is closely correlated with
migration and invasion by epithelial-to-mesenchymal transition (EMT) modulation.
Activated GTSE1 significantly interferes with chemotherapy efficacy and
influences the probability of survival of patients with HCC. GTSE1 may thus
represent a promising molecular target.
PMID- 28698582
TI - Regional and local environmental conditions do not shape the response to warming
of a marine habitat-forming species.
AB - The differential response of marine populations to climate change remains poorly
understood. Here, we combine common garden thermotolerance experiments in aquaria
and population genetics to disentangle the factors driving the population
response to thermal stress in a temperate habitat-forming species: the octocoral
Paramuricea clavata. Using eight populations separated from tens of meters to
hundreds of kilometers, which were differentially impacted by recent mortality
events, we identify 25 degrees C as a critical thermal threshold. After one week
of exposure at this temperature, seven of the eight populations were affected by
tissue necrosis and after 30 days of exposure at this temperature, the mean % of
affected colonies increased gradually from 3 to 97%. We then demonstrate the weak
relation between the observed differential phenotypic responses and the local
temperature regimes experienced by each population. A significant correlation was
observed between these responses and the extent of genetic drift impacting each
population. Local adaptation may thus be hindered by genetic drift, which seems
to be the main driver of the differential response. Accordingly, conservation
measures should promote connectivity and control density erosion in order to
limit the impact of genetic drift on marine populations facing climate change.
PMID- 28698583
TI - Ammonium chloride alters neuronal excitability and synaptic vesicle release.
AB - Genetically encoded pH-sensors are widely used in studying cell membrane
trafficking and membrane protein turnover because they render exo-/endocytosis
associated pH changes to fluorescent signals. For imaging and analysis purposes,
high concentration ammonium chloride is routinely used to alkalize intracellular
membrane compartments under the assumption that it does not cause long-term
effects on cellular processes being studied like neurotransmission. However,
pathological studies about hyperammonemia have shown that ammonium is toxic to
brain cells especially astrocytes and neurons. Here, we focus on ammonium's
physiological impacts on neurons including membrane potential, cytosolic Ca2+ and
synaptic vesicles. We have found that extracellularly applied ammonium chloride
as low as 5 mM causes intracellular Ca2+-increase and a reduction of vesicle
release even after washout. The often-used 50 mM ammonium chloride causes more
extensive and persistent changes, including membrane depolarization, prolonged
elevation of intracellular Ca2+ and diminution of releasable synaptic vesicles.
Our findings not only help to bridge the discrepancies in previous studies about
synaptic vesicle release using those pH-sensors or other vesicle specific
reporters, but also suggest an intriguing relationship between intracellular pH
and neurotransmission.
PMID- 28698584
TI - A novel STK1-targeted small-molecule as an "antibiotic resistance breaker"
against multidrug-resistant Staphylococcus aureus.
AB - Ser/Thr protein kinase (STK1) plays a critical role in cell wall biosynthesis of
and drug resistance in methicillin-resistant Staphylococcus aureus (MRSA). MRSA
strains lacking STK1 become susceptible to failing cephalosporins, such as
Ceftriaxone and Cefotaxime. STK1, despite being nonessential protein for MRSA
survival, it can serve as an important therapeutic agent for combination therapy.
Here, we report a novel small molecule quinazoline compound, Inh2-B1, which
specifically inhibits STK1 activity by directly binding to its ATP-binding
catalytic domain. Functional analyses encompassing in vitro growth inhibition of
MRSA, and in vivo protection studies in mice against the lethal MRSA challenge
indicated that at high concentration neither Inh2-B1 nor Ceftriaxone or
Cefotaxime alone was able to inhibit the growth of bacteria or protect the
challenged mice. However, the growth of MRSA was inhibited, and a significant
protection in mice against the bacterial challenge was observed at a micromolar
concentration of Ceftriaxone or Cefotaxime in the presence of Inh2-B1. Cell
dependent minimal to no toxicity of Inh2-B1, and its abilities to down-regulate
cell wall hydrolase genes and disrupt the biofilm formation of MRSA clearly
indicated that Inh2-B1 serves as a therapeutically important "antibiotic
resistance-breaker," which enhances the bactericidal activity of
Ceftriaxone/Cefotaxime against highly pathogenic MRSA infection.
PMID- 28698585
TI - Effects of Aortic Valve Replacement on Severe Aortic Stenosis and Preserved
Systolic Function: Systematic Review and Network Meta-analysis.
AB - The survival benefits of aortic valve replacement (AVR) in the different flow
gradient states of severe aortic stenosis (AS) is not known. A comprehensive
search in PubMed/MEDLINE, Embase, Cochrane Library, CNKI and OpenGrey were
conducted to identify studies that investigated the prognosis of severe AS
(effective orifice area <=1.0 cm2) and left ventricular ejection fraction >=50%.
Severe AS was stratified by mean pressure gradient [threshold of 40 mmHg; high
gradient (HG) and low-gradient (LG)] and stroke volume index [threshold of 35
ml/m2; normal-flow (NL) and low-flow (LF)]. Network meta-analysis was conducted
to assess all-cause mortality among each AS sub-type with rate ratio (RR)
reported. The effects of AVR on prognosis were examined using network meta
regression. In the pooled analysis (15 studies and 9,737 patients), LF states
(both HG and LG) were associated with increased mortality rate (LFLG: RR 1.88;
95% CI: 1.43-2.46; LFHG: RR: 1.77; 95% CI: 1.16-2.70) compared to moderate AS;
and NF states in both HG and LG had similar prognosis as moderate AS (NFLG: RR
1.11; 95% CI: 0.81-1.53; NFHG: RR 1.16; 95% CI: 0.82-1.64). AVR conferred
different survival benefits: it was most effective in NFHG (RR with AVR /RR
without AVR : 0.43; 95% CI: 0.22-0.82) and least in LFLG (RR with AVR /RR without
AVR : 1.19; 95% CI: 0.74-1.94).
PMID- 28698586
TI - Sensitization, energy transfer and infra-red emission decay modulation in Yb3+
doped NaYF4 nanoparticles with visible light through a perfluoroanthraquinone
chromophore.
AB - Infra-red emission (980 nm) of sub 10 nm Yb3+-doped NaYF4 nanoparticles has been
sensitized through the excitation of 2-hydroxyperfluoroanthraquinone chromophore
(1,2,3,4,5,6,7-heptafluro-8-hydroxyanthracene-9,10-dione) functionalizing the
nanoparticle surface. The sensitization is achieved with a broad range of visible
light excitation (400-600 nm). The overall near infra-red (NIR) emission
intensity of Yb3+ ions is increased by a factor 300 as a result of the broad and
strong absorption of the chromophore compared with ytterbium's intrinsic
absorption. Besides the Yb3+ NIR emission, the hybrid composite shows organic
chromophore-based visible emission in the orange-red region of the spectrum. We
observe the energy migration process from the sensitized Yb3+ ions at the surface
to those in the core of the particle using time-resolved optical spectroscopy.
This highlights that the local environments for emitting Yb3+ ions at the surface
and center of the nanoparticle are not identical, which causes important
differences in the NIR emission dynamics. Based on the understanding of these
processes, we suggest a simple strategy to control and modulate the decay time of
the functionalized Yb3+-doped nanoparticles over a relatively large range by
changing physical or chemical parameters in this model system.
PMID- 28698587
TI - A Novel Dual Eigen-Analysis of Mouse Multi-Tissues' Expression Profiles Unveils
New Perspectives into Type 2 Diabetes.
AB - Type 2 diabetes (T2D) is a complex and polygenic disease yet in need of a
complete picture of its development mechanisms. To better understand the
mechanisms, we examined gene expression profiles of multi-tissues from outbred
mice fed with a high-fat diet (HFD) or regular chow at weeks 1, 9, and 18. To
analyze such complex data, we proposed a novel dual eigen-analysis, in which the
sample- and gene-eigenvectors correspond respectively to the macro- and micro
biology information. The dual eigen-analysis identified the HFD eigenvectors as
well as the endogenous eigenvectors for each tissue. The results imply that HFD
influences the hepatic function or the pancreatic development as an exogenous
factor, while in adipose HFD's impact roughly coincides with the endogenous
eigenvector driven by aging. The enrichment analysis of the eigenvectors revealed
diverse HFD impact on the three tissues over time. The diversity includes:
inflammation, degradation of branched chain amino acids (BCAA), and regulation of
peroxisome proliferator activated receptor gamma (PPARgamma). We reported that in
the pancreas remarkable up-regulation of angiogenesis as downstream of the HIF
signaling pathway precedes hyperinsulinemia. The dual eigen-analysis and
discoveries provide new evaluations/guidance in T2D prevention and therapy, and
will also promote new thinking in biology and medicine.
PMID- 28698588
TI - Mutual influence between current-induced giant magnetoresistance and radiation
induced magnetoresistance oscillations in the GaAs/AlGaAs 2DES.
AB - Radiation-induced magnetoresistance oscillations are examined in the GaAs/AlGaAs
2D system in the regime where an observed concurrent giant magnetoresistance is
systematically varied with a supplementary dc-current, I dc . The I dc tuned
giant magnetoresistance is subsequently separated from the photo-excited
oscillatory resistance using a multi-conduction model in order to examine the
interplay between the two effects. The results show that the invoked
multiconduction model describes the observed giant magnetoresistance effect even
in the presence of radiation-induced magnetoresistance oscillations, the
magnetoresistance oscillations do not modify the giant magnetoresistance, and the
magnetoresistance oscillatory extrema, i.e., maxima and minima, disappear rather
asymmetrically with increasing I dc . The results suggest the interpretation that
the I dc serves to suppress scattering between states near the Fermi level in a
strong magnetic field limit.
PMID- 28698589
TI - Transglycosylation by a chitinase from Enterobacter cloacae subsp. cloacae
generates longer chitin oligosaccharides.
AB - Humans have exploited natural resources for a variety of applications. Chitin and
its derivative chitin oligosaccharides (CHOS) have potential biomedical and
agricultural applications. Availability of CHOS with the desired length has been
a major limitation in the optimum use of such natural resources. Here, we report
a single domain hyper-transglycosylating chitinase, which generates longer CHOS,
from Enterobacter cloacae subsp. cloacae 13047 (EcChi1). EcChi1 was optimally
active at pH 5.0 and 40 degrees C with a Km of 15.2 mg ml-1, and k cat/Km of
0.011* 102 mg-1 ml min-1 on colloidal chitin. The profile of the hydrolytic
products, major product being chitobiose, released from CHOS indicated that
EcChi1 was an endo-acting enzyme. Transglycosylation (TG) by EcChi1 on trimeric
to hexameric CHOS resulted in the formation of longer CHOS for a prolonged
duration. EcChi1 showed both chitobiase and TG activities, in addition to
hydrolytic activity. The TG by EcChi1 was dependent, to some extent, on the
length of the CHOS substrate and concentration of the enzyme. Homology modeling
and docking with CHOS suggested that EcChi1 has a deep substrate-binding groove
lined with aromatic amino acids, which is a characteristic feature of a
processive enzyme.
PMID- 28698590
TI - Tudor Domain Containing Protein 3 Promotes Tumorigenesis and Invasive Capacity of
Breast Cancer Cells.
AB - Tudor domain containing protein 3 (TDRD3) is a modular protein identified based
on its ability to recognize methylated arginine motifs through its Tudor domain.
We have previously shown that TDRD3 localizes to cytoplasmic stress granules, a
structure shown to promote survival upon treatment with chemotherapeutic drugs in
cancer cells. Here, we report TDRD3 as a novel regulator of cell proliferation
and invasion in breast cancer cells. Our study also demonstrates that TDRD3
depletion inhibits tumor formation and metastasis to the lung in vivo.
Furthermore, we show that TDRD3 regulates the expression of a number of key genes
associated with promotion of breast cancer tumorigenesis and disease progression.
Strikingly, we report that TDRD3 regulates some of these key targets at the level
of translation. These findings provide the first experimental demonstration of a
functional role for TDRD3 in promoting breast cancer development and progression,
and identify TDRD3 as a potential new therapeutic target for breast cancer.
PMID- 28698591
TI - Molecular dynamics study on the mechanism of polynucleotide encapsulation by
chitosan.
AB - The safe and effective delivery of therapeutic genes into target cell interiors
is of great importance in gene therapy. Chitosan has been extensively studied as
a gene delivery carrier due to its good biocompatibility and biodegradability.
Understanding the atomic interaction mechanism between chitosan and DNA is
important in the design and application of chitosan-based drug and gene delivery
systems. In this work, the interactions between single-stranded polynucleotides
and different types of chitosan were systematically investigated by using
molecular dynamics (MD) simulation. Our results demonstrate that the functional
groups of chitosan, the types of base and length of polynucleotides regulate the
interaction behavior between chitosan and polynucleotides. The encapsulation
capacity of polynucleotide by chitosan is mainly balanced by two factors: the
strength of polynucleotide binding to chitosan and the tendency of self
aggregation of polynucleotide in the solution. For -NH3+ chitosan, due to the
strong electrostatic interaction, especially the H-bond between -NH3+ groups in
chitosan and phosphate groups in polynucleotide, the aggregation effect could be
partially eliminated. The good dispersal capacity of polynucleotides may improve
the encapsulation of polynucleotides by chitosan, and hence increase the delivery
and transfection efficiency of chitosan-based gene carrier.
PMID- 28698592
TI - Monitoring changes of docosahexaenoic acid-containing lipids during the recovery
process of traumatic brain injury in rat using mass spectrometry imaging.
AB - Brain lipid homoeostasis is critical during recovery process after traumatic
brain injury (TBI). In this study, we integrated liquid extraction and
electrosonic spray ionization technology to develop an ionization device coupled
with a Fourier transform ion cyclotron resonance mass spectrometer for imaging of
docosahexaenoic acid (DHA)-containing lipids on rat brain tissues. The ion images
of the brain tissue sections from the normal rats and the rats after TBI at acute
phase (0 and 1 day) and chronic phase (3, 5, and 7 days) were obtained. The
imaging results indicate that the levels of DHA and lyso-phosphatidylethanolamine
(22:6) in the injury area of TBI rats increased significantly at the acute phase
and subsequently decreased at the chronic phase. But the levels of DHA-containing
phospholipids including phosphatidylethanolamine (PE)(P-18:0/22:6),
PE(18:0/22:6), and phosphatidylserine (18:0/22:6) decreased at the acute phase
and gradually increased at the chronic phase in the injury area accompanied by
the morphogenesis and wound healing. These findings indicate that the DHA may
participate in the recovery process of brain injury. This is the first report to
in situ detect the changes in the levels of DHA and DHA-containing lipids in the
TBI model.
PMID- 28698593
TI - Differential adiponectin signalling couples ER stress with lipid metabolism to
modulate ageing in C. elegans.
AB - The metabolic and endocrine functions of adipose tissue and the ability of
organisms to cope with cellular stress have a direct impact on physiological
ageing and the aetiology of various diseases such as obesity-related pathologies
and cancer. The endocrine effects of adipose tissue are mediated by secreted
adipokines, which modulate metabolic processes and influence related maladies.
Although a plethora of molecules and signaling pathways associate ageing with
proteotoxic stress and cellular metabolism, our understanding of how these
pathways interconnect to coordinate organismal physiology remains limited. We
dissected the mechanisms linking adiponectin signalling pathways and endoplasmic
reticulum (ER) proteotoxic stress responses that individually or synergistically
affect longevity in C. elegans. Animals deficient for the adiponectin receptor
PAQR-1 respond to ER stress, by rapidly activating the canonical ER unfolded
protein response (UPRER) pathway, which is primed in these animals under
physiological conditions by specific stress defence transcription factors. PAQR-1
loss enhances survival and promotes longevity under ER stress and reduced
insulin/IGF-1 signalling. PAQR-1 engages UPRER, autophagy and lipase activity to
modulate lipid metabolism during ageing. Our findings demonstrate that moderating
adiponectin receptor -1 activity extends lifespan under stress, and directly
implicate adiponectin signalling as a coupler between proteostasis and lipid
metabolism during ageing.
PMID- 28698594
TI - Semantic congruent audiovisual integration during the encoding stage of working
memory: an ERP and sLORETA study.
AB - Although multisensory integration is an inherent component of functional brain
organization, multisensory integration during working memory (WM) has attracted
little attention. The present study investigated the neural properties underlying
the multisensory integration of WM by comparing semantically related bimodal
stimulus presentations with unimodal stimulus presentations and analysing the
results using the standardized low-resolution brain electromagnetic tomography
(sLORETA) source location approach. The results showed that the memory retrieval
reaction times during congruent audiovisual conditions were faster than those
during unisensory conditions. Moreover, our findings indicated that the event
related potential (ERP) for simultaneous audiovisual stimuli differed from the
ERP for the sum of unisensory constituents during the encoding stage and occurred
within a 236-530 ms timeframe over the frontal and parietal-occipital electrodes.
The sLORETA images revealed a distributed network of brain areas that participate
in the multisensory integration of WM. These results suggested that information
inputs from different WM subsystems yielded nonlinear multisensory interactions
and became integrated during the encoding stage. The multicomponent model of WM
indicates that the central executive could play a critical role in the
integration of information from different slave systems.
PMID- 28698595
TI - The Gene Variants of Maternal/Fetal Renin-Angiotensin System in Preeclampsia: A
Hybrid Case-Parent/Mother-Control Study.
AB - Preeclampsia (PE) is a common pregnancy-related complication, and polymorphisms
in angiotensinogen (AGT), angiotensin-converting enzyme (ACE), and angiotensin II
type 1 receptor (AT1R) are believed to contribute to PE development. We
implemented a hybrid study to investigate the influence of maternal and fetal ACE
I/D, ACE G2350A, AGT M235T, AGT T174M, and AT1R A1166C polymorphisms on PE in Han
Chinese women. Polymorphisms were genotyped in 1,488 subjects (256 patients
experiencing PE, along with their fetuses and partners, and 360 normotensive
controls with their fetuses). Transmission disequilibrium tests revealed that ACE
I/D (P = 0.041), ACE G2350A (P = 0.035), and AT1R A1166C (P = 0.018) were
associated with maternal PE. The log-linear analyses revealed that mothers whose
offspring carried the MM genotype of AGT M235T had a higher risk of PE (OR =
1.54, P = 0.010), whereas mothers whose offspring carried the II genotype of ACE
I/D or the GG genotype of ACE G2350A had a reduced risk (OR = 0.58, P = 0.039; OR
= 0.47, P = 0.045, respectively). Our findings demonstrate that fetal ACE I/D,
ACE G2350A, AGT M235T, and AT1R A1166C polymorphisms may play significant roles
in PE development among pregnant Han Chinese women.
PMID- 28698596
TI - Aerobic fitness associates with mnemonic discrimination as a mediator of physical
activity effects: evidence for memory flexibility in young adults.
AB - A physically active lifestyle has beneficial effects on hippocampal memory
function. A potential mechanism for this effect is exercise-enhanced hippocampal
plasticity, particularly in the dentate gyrus (DG). Within hippocampal memory
formation, the DG plays a crucial role in pattern separation, which is the
ability to discriminate among similar experiences. Computational models propose a
theoretical hypothesis that enhanced DG-mediated pattern separation leads to
"memory flexibility"-a selective improvement in the ability to overcome moderate
levels of mnemonic interference. Thus, in the current cross-sectional study of
healthy young adults, we tested the working hypothesis that aerobic fitness, as a
physiological indicator of endurance capacity associated with physical activity,
is strongly associated with mnemonic discrimination at moderate interference
levels. When divided the sample (n = 75) based on a median split of aerobic
fitness, the higher fitness group had better discrimination performance for
moderate interference levels compared to the lower fitness group, namely,
exhibited memory flexibility. Moreover, aerobic fitness levels were positively
associated with discrimination performance for moderate interference levels, as a
mediator of physical activity effects. This evidence suggests that aerobic
fitness levels are associated with hippocampal DG-related memory, which is
consistent with literature showing positive effect of physical exercise on
hippocampal memory.
PMID- 28698597
TI - Selenoprotein MsrB1 promotes anti-inflammatory cytokine gene expression in
macrophages and controls immune response in vivo.
AB - Post-translational redox modification of methionine residues often triggers a
change in protein function. Emerging evidence points to this reversible protein
modification being an important regulatory mechanism under various physiological
conditions. Reduction of oxidized methionine residues is catalyzed by methionine
sulfoxide reductases (Msrs). Here, we show that one of these enzymes, a selenium
containing MsrB1, is highly expressed in immune-activated macrophages and
contributes to shaping cellular and organismal immune responses. In particular,
lipopolysaccharide (LPS) induces expression of MsrB1, but not other Msrs. Genetic
ablation of MsrB1 did not preclude LPS-induced intracellular signaling in
macrophages, but resulted in attenuated induction of anti-inflammatory cytokines,
such as interleukin (IL)-10 and the IL-1 receptor antagonist. This anomaly was
associated with excessive pro-inflammatory cytokine production as well as an
increase in acute tissue inflammation in mice. Together, our findings suggest
that MsrB1 controls immune responses by promoting anti-inflammatory cytokine
expression in macrophages. MsrB1-dependent reduction of oxidized methionine in
proteins may be a heretofore unrecognized regulatory event underlying immunity
and inflammatory disease, and a novel target for clinical applications.
PMID- 28698598
TI - Classification and function of small open reading frames.
AB - Small open reading frames (smORFs) of 100 codons or fewer are usually - if
arbitrarily - excluded from proteome annotations. Despite this, the genomes of
many metazoans, including humans, contain millions of smORFs, some of which
fulfil key physiological functions. Recently, the transcriptome of Drosophila
melanogaster was shown to contain thousands of smORFs of different classes that
actively undergo translation, which produces peptides of mostly unknown function.
Here, we present a comprehensive analysis of smORFs in flies, mice and humans. We
propose the existence of several functional classes of smORFs, ranging from inert
DNA sequences to transcribed and translated cis-regulators of translation and
peptides with a propensity to function as regulators of membrane-associated
proteins, or as components of ancient protein complexes in the cytoplasm. We
suggest that the different smORF classes could represent steps in gene, peptide
and protein evolution. Our analysis introduces a distinction between different
peptide-coding classes of smORFs in animal genomes, and highlights the role of
model organisms for the study of small peptide biology in the context of
development, physiology and human disease.
PMID- 28698600
TI - Transcriptional and epigenetic control of brown and beige adipose cell fate and
function.
PMID- 28698599
TI - Genes and molecular pathways underpinning ciliopathies.
AB - Motile and non-motile (primary) cilia are nearly ubiquitous cellular organelles.
The dysfunction of cilia causes diseases known as ciliopathies. The number of
reported ciliopathies (currently 35) is increasing, as is the number of
established (187) and candidate (241) ciliopathy-associated genes. The
characterization of ciliopathy-associated proteins and phenotypes has improved
our knowledge of ciliary functions. In particular, investigating ciliopathies has
helped us to understand the molecular mechanisms by which the cilium-associated
basal body functions in early ciliogenesis, as well as how the transition zone
functions in ciliary gating, and how intraflagellar transport enables cargo
trafficking and signalling. Both basic biological and clinical studies are
uncovering novel ciliopathies and the ciliary proteins involved. The assignment
of these proteins to different ciliary structures, processes and ciliopathy
subclasses (first order and second order) provides insights into how this
versatile organelle is built, compartmentalized and functions in diverse ways
that are essential for human health.
PMID- 28698601
TI - Characteristics of Sonography in a Rat Achilles Tendinopathy Model: Possible Non
invasive Predictors of Biomechanics.
AB - The purpose of this study was to investigate the dynamic changes of
histopathology, biomechanical properties, echo intensity, and ultrasound features
in a collagenase-induced tendinopathy model of rat Achilles tendons, and to
examine the associations among biomechanical properties, echo intensity, and
ultrasound features. Forty-two rats received an ultrasound-guided collagenase
injection on their left Achilles tendons, and needle puncture on the right ones
as the control. At four, eight, and twelve weeks post-injury, the tendons were
examined via measurements of their biomechanical properties, histopathological
and ultrasonographic characteristics. The injured tendons showed significantly
higher histopathological scores, lower Young's modulus, and higher ultrasound
feature scores than the those of control ones throughout the study period. Up to
week 12, all injured tendons showed defective healing. The neovascularization
score had a significant negative linear association with the failure stress and
Young's modulus. Maximum normalized echo intensity had a significant positive
linear association with maximum strain. Therefore, neovascularization and maximum
normalized echo intensity are associated with mechanically altered tendinopathic
tendons. Non-invasive ultrasound methodology, including echo intensity and
ultrasound feature scores, may provide useful information about biomechanical
properties of tendinopathic tendons.
PMID- 28698602
TI - Polyglutamine expansion affects huntingtin conformation in multiple Huntington's
disease models.
AB - Conformational changes in disease-associated or mutant proteins represent a key
pathological aspect of Huntington's disease (HD) and other protein misfolding
diseases. Using immunoassays and biophysical approaches, we and others have
recently reported that polyglutamine expansion in purified or recombinantly
expressed huntingtin (HTT) proteins affects their conformational properties in a
manner dependent on both polyglutamine repeat length and temperature but
independent of HTT protein fragment length. These findings are consistent with
the HD mutation affecting structural aspects of the amino-terminal region of the
protein, and support the concept that modulating mutant HTT conformation might
provide novel therapeutic and diagnostic opportunities. We now report that the
same conformational TR-FRET based immunoassay detects polyglutamine- and
temperature-dependent changes on the endogenously expressed HTT protein in
peripheral tissues and post-mortem HD brain tissue, as well as in tissues from HD
animal models. We also find that these temperature- and polyglutamine-dependent
conformational changes are sensitive to bona-fide phosphorylation on S13 and S16
within the N17 domain of HTT. These findings provide key clinical and preclinical
relevance to the conformational immunoassay, and provide supportive evidence for
its application in the development of therapeutics aimed at correcting the
conformation of polyglutamine-expanded proteins as well as the pharmacodynamics
readouts to monitor their efficacy in preclinical models and in HD patients.
PMID- 28698603
TI - Identification of differentially methylated BRCA1 and CRISP2 DNA regions as blood
surrogate markers for cardiovascular disease.
AB - Genome-wide Illumina InfiniumMethylation 450 K DNA methylation analysis was
performed on blood samples from clinical atherosclerosis patients (n = 8) and
healthy donors (n = 8) in the LVAD study (NCT02174133, NCT01799005). Multiple
differentially methylated regions (DMR) could be identified in atherosclerosis
patients, related to epigenetic control of cell adhesion, chemotaxis,
cytoskeletal reorganisations, cell proliferation, cell death, estrogen receptor
pathways and phagocytic immune responses. Furthermore, a subset of 34 DMRs
related to impaired oxidative stress, DNA repair, and inflammatory pathways could
be replicated in an independent cohort study of donor-matched healthy and
atherosclerotic human aorta tissue (n = 15) and human carotid plaque samples (n =
19). Upon integrated network analysis, BRCA1 and CRISP2 DMRs were identified as
most central disease-associated DNA methylation biomarkers. Differentially
methylated BRCA1 and CRISP2 regions were verified by MassARRAY Epityper and
pyrosequencing assays and could be further replicated in blood, aorta tissue and
carotid plaque material of atherosclerosis patients. Moreover, methylation
changes at BRCA1 and CRISP2 specific CpG sites were consistently associated with
subclinical atherosclerosis measures (coronary calcium score and carotid intima
media thickness) in an independent sample cohort of middle-aged men with
subclinical cardiovascular disease in the Aragon Workers' Health Study (n = 24).
Altogether, BRCA1 and CRISP2 DMRs hold promise as novel blood surrogate markers
for early risk stratification and CVD prevention.
PMID- 28698604
TI - Honeybee (Apis mellifera)-associated bacterial community affected by American
foulbrood: detection of Paenibacillus larvae via microbiome analysis.
AB - Honeybee (Apis mellifera L.) workers act as passive vectors of Paenibacillus
larvae spores, which cause the quarantine disease American foulbrood (AFB). We
assessed the relative proportions of P. larvae within the honeybee microbiome
using metabarcoding analysis of the 16 S rRNA gene. The microbiome was analyzed
in workers outside of the AFB zone (control - AFB0), in workers from asymptomatic
colonies in an AFB apiary (AFB1), and in workers from colonies exhibiting
clinical AFB symptoms (AFB2). The microbiome was processed for the entire
community and for a cut-off microbiome comprising pathogenic/environmental
bacteria following the removal of core bacterial sequences; varroosis levels were
considered in the statistical analysis. No correlation was observed between AFB
status and varroosis level, but AFB influenced the worker bee bacterial
community, primarily the pathogenic/environmental bacteria. There was no
significant difference in the relative abundance of P. larvae between the AFB1
and AFB0 colonies, but we did observe a 9-fold increase in P. larvae abundance in
AFB2 relative to the abundance in AFB1. The relative sequence numbers of
Citrobacter freundii and Hafnia alvei were higher in AFB2 and AFB1 than in AFB0,
whereas Enterococcus faecalis, Klebsiella oxytoca, Spiroplasma melliferum and
Morganella morganii were more abundant in AFB0 and AFB1 than in AFB2.
PMID- 28698605
TI - Appearance of Unstable Monopoly State Caused by Selective and Concentrative
Mergers in Business Networks.
AB - Recently, growth mechanism of firms in complex business networks became new
targets of scientific study owing to increasing availability of high quality
business firms' data. Here, we paid attention to comprehensive data of M&A events
for 40 years and derived empirical laws by applying methods and concepts of
aggregation dynamics of aerosol physics. It is found that the probability of
merger between bigger firms is bigger than that between smaller ones, and such
tendency is enhancing year by year. We introduced a numerical model simulating
the whole ecosystem of firms and showed that the system is already in an unstable
monopoly state in which growth of middle sized firms are suppressed.
PMID- 28698606
TI - Reading-induced shifts of perceptual speech representations in auditory cortex.
AB - Learning to read requires the formation of efficient neural associations between
written and spoken language. Whether these associations influence the auditory
cortical representation of speech remains unknown. Here we address this question
by combining multivariate functional MRI analysis and a newly-developed 'text
based recalibration' paradigm. In this paradigm, the pairing of visual text and
ambiguous speech sounds shifts (i.e. recalibrates) the perceptual interpretation
of the ambiguous sounds in subsequent auditory-only trials. We show that it is
possible to retrieve the text-induced perceptual interpretation from fMRI
activity patterns in the posterior superior temporal cortex. Furthermore, this
auditory cortical region showed significant functional connectivity with the
inferior parietal lobe (IPL) during the pairing of text with ambiguous speech.
Our findings indicate that reading-related audiovisual mappings can adjust the
auditory cortical representation of speech in typically reading adults.
Additionally, they suggest the involvement of the IPL in audiovisual and/or
higher-order perceptual processes leading to this adjustment. When applied in
typical and dyslexic readers of different ages, our text-based recalibration
paradigm may reveal relevant aspects of perceptual learning and plasticity during
successful and failing reading development.
PMID- 28698607
TI - Divergent evolution of Di-lysine ER retention vs. farnesylation motif-mediated
anchoring of the AnkB virulence effector to the Legionella-containing vacuolar
membrane.
AB - Within macrophages and amoeba, the Legionella-containing vacuole (LCV) membrane
is derived from the ER. The bona fide F-box AnkB effector protein of L.
pneumophila strain AA100/130b is anchored to the cytosolic side of the LCV
membrane through host-mediated farnesylation of its C-terminal eukaryotic "CaaX"
motif. Here we show that the AnkB homologue of the Paris strain has a frame shift
mutation that led to a loss of the CaaX motif and a concurrent generation of a
unique C-terminal KNKYAP motif, which resembles the eukaryotic di-lysine ER
retention motif (KxKxx). Our phylogenetic analyses indicate that environmental
isolates of L. pneumophila have a potential positive selection for the ER
retention KNKYAP motif. The AnkB-Paris effector is localized to the LCV membrane
most likely through the ER-retention motif. Its ectopic expression in HEK293T
cells localizes it to the perinuclear ER region and it trans-rescues the ankB
mutant of strain AA100/130b in intra-vacuolar replication. The di-lysine ER
retention motif of AnkB-Paris is indispensable for function; most likely as an ER
retention motif that enables anchoring to the ER-derived LCV membrane. Our
findings show divergent evolution of the ankB allele in exploiting either host
farnesylation or the ER retention motif to be anchored into the LCV membrane.
PMID- 28698608
TI - Wall slipping behavior of foam with nanoparticle-armored bubbles and its flow
resistance factor in cracks.
AB - In this work, wall slipping behavior of foam with nanoparticle-armored bubbles
was first studied in a capillary tube and the novel multiphase foam was
characterized by a slipping law. A crack model with a cuboid geometry was then
used to compare with the foam slipping results from the capillary tube and also
to evaluate the flow resistance factor of the foam. The results showed that the
slipping friction force F FR in the capillary tube significantly increased by
addition of modified SiO2 nanoparticles, and an appropriate power law exponents
by fitting F FR vs. Capillary number, Ca, was 1/2. The modified nanoparticles at
the surface were bridged together and formed a dense particle "armor" surrounding
the bubble, and the interconnected structures of the "armor" with strong steric
integrity made the surface solid-like, which was in agreement with the slip
regime associated with rigid surface. Moreover, as confirmed by 3D microscopy,
the roughness of the bubble surface increased with nanoparticle concentration,
which in turn increased the slipping friction force. Compared with pure SDBS
foam, SDBS/SiO2 foam shows excellent stability and high flow resistance in visual
crack. The resistance factor of SiO2/SDBS foam increased as the wall surface
roughness increased in core cracks.
PMID- 28698609
TI - Functional analyses of a novel missense and other mutations of the vitamin D
receptor in association with alopecia.
AB - Hereditary 1,25-dihydroxyvitamin D-resistant rickets (HVDRR) is a rare disorder,
caused by bialellic mutations of the vitamin D receptor (VDR) gene, sometimes
associated with alopecia. The aim of this study is to elucidate the mechanism of
functional disruption of a novel mutation, detected in a patient with HVDRR,
comparing to other mutations with or without alopecia. The patient was a 2-year
old girl with alopecia, who was clinically diagnosed as HVDRR. Genetic analysis
revealed a novel homozygous mutation, S360P, located in ligand binding domain
(LBD). The mutation was predicted as not disease causing by Polyphen2 and SIFT.
But the transcriptional activity of S360P was disrupted as well as other reported
mutations, Q152X (located in the hinge lesion), and R274L, H305Q (located in
LBD). Following assays revealed no ligand binding affinity, no interaction with
cofactors or RXR and no functioning of nuclear localization signals. Our results
provide an additional evidence for the previous findings suggesting that DNA
binding by the VDR/RXR heterodimer is essential for the function of the VDR in
hair development. In conclusion, we identified a novel missense mutation of VDR
causing HVDRR with alopecia. Functional analyses revealed that the single amino
acid substitution could disrupt the function of the protein.
PMID- 28698610
TI - Tomatoes protect against development of UV-induced keratinocyte carcinoma via
metabolomic alterations.
AB - Prolonged tomato consumption can mitigate ultraviolet (UV) light induced sunburn
via unknown mechanisms. Dietary carotenoids distributed to skin are hypothesized
to protect skin against UV-induced damage, although other phytochemicals may play
a role. We hypothesize that tomato consumption would protect against skin cancer.
SKH-1 hairless and immunocompetent mice (n = 180) were fed AIN-93G or AIN-93G +
10% tangerine or red tomato powder for 35 weeks. From weeks 11-20, mice (n = 120)
were exposed to 2240 J/m2 UV-B light, 3x/week, and tumors were tracked weekly.
Control mice were fed the same diets but not exposed to UV. Tumor number was
significantly lower in male mice consuming red tomato diets (1.73 +/- 0.50, P =
0.015) or pooled tomato diets (2.03 +/- 0.45, P = 0.017) compared to controls
(4.04 +/- 0.65). Carotenoid levels in plasma and skin were quantitated, with
total lycopene higher in skin of tangerine fed animals despite a lower dose.
Metabolomic analyses elucidated compounds derived from tomato glycoalkaloids
(including tomatidine and hydroxylated-tomatidine) as significantly different
metabolites in skin after tomato exposure. Here, we describe that tomato
consumption can modulate risk for keratinocyte carcinomas; however, the role of
the newly identified specific phytochemicals possibly responsible for this action
require further investigation.
PMID- 28698611
TI - Flavonoid Enhances the Glyoxalase Pathway in Cerebellar Neurons to Retain
Cellular Functions.
AB - Oxidative stress is damaging to cells and contributes to aging and
neurodegenerative disease. This state is mediated by production of imbalanced
molecules, and reactive dicarbonyl compounds - mainly methylglyoxal. The
glyoxalase pathway is an antioxidant defense system utilized to detoxify
methylglyoxal and neutralize free radicals. Pathway dysfunction leads to
overproduction and accumulation of toxic, prooxidant compounds. We hypothesize
flavonoid treatment as a means to enhance the glyoxalase pathway's ability to
detoxify in neurons. This study found that flavonoid treatment in methylglyoxal
treated cerebellar neurons increased the functioning of glyoxalase pathway by
enhancing expression of glyoxalase-1 and glyoxalase-2 proteins, decreased cell
death and increased cellular viability. Flavonoids also significantly contributed
in the retention of synaptic functions (VGLUT1 and GAD65) in cerebellar neurons.
In addition, flavonoids were found to be involved in pAkt - NF-kappaB signaling
pathway through a reduction in phosphorylation of Akt. The data here show
flavonoid compounds have the potential to protect the brain from aging and
neurodegenerative disease.
PMID- 28698612
TI - eIF2alpha signaling regulates ischemic osteonecrosis through endoplasmic
reticulum stress.
AB - Osteonecrosis of the femoral head (ONFH) primarily results from ischemia/hypoxia
to the femoral head, and one of the cellular manifestations is the endoplasmic
reticulum (ER) stress. To understand possible linkage of ischemic osteonecrosis
to the ER stress, a surgery-induced animal model was employed and salubrinal was
administered to evaluate the role of ER stress. Salubrinal is a synthetic
chemical that inhibits de-phosphorylation of eIF2alpha, and it can suppress cell
death from the ER stress at a proper dose. The results indicated that the ER
stress was associated with ONFH and salubrinal significantly improved ONFH
induced symptoms such as osteonecrosis, bone loss, reduction in vessel perfusion,
and excessive osteoclastogenesis in the femoral head. Salubrinal also protected
osteoblast development by upregulating the levels of ATF4, ALP and RUNX2, and it
stimulated angiogenesis of endothelial cells through elevating ATF4 and VEGF.
Collectively, the results support the notion that the ER stress is an important
pathological outcome in the surgery-induced ONFH model, and salubrinal improves
ONFH symptoms by enhancing angiogenesis and bone healing via suppressing the ER
stress.
PMID- 28698613
TI - Transcriptome and metabolite analyses in Azadirachta indica: identification of
genes involved in biosynthesis of bioactive triterpenoids.
AB - Azadirachta indica A. Juss, commonly known as Neem, is the reservoir of
triterpenoids of economic importance. Metabolite analysis of different
developmental stages of leaf and fruit suggests tissue-specific accumulation of
the major triterpenoids in this important tree. Though biosynthesis of these
complex molecules requires substrate flux from the isoprenoid pathway, enzymes
involved in late biosynthetic steps remain uncharacterized. We established and
analyzed transcriptome datasets from leaf and fruit and identified members of
gene families involved in intermediate steps of terpenoid backbone biosynthesis
and those related to secondary transformation leading to the tissue-specific
triterpenoid biosynthesis. Expression analysis suggests differential expression
of number of genes between leaf and fruit and probable participation in the
biosynthesis of fruit-specific triterpenoids. Genome-wide analysis also
identified members of gene families putatively involved in secondary
modifications in late biosynthetic steps leading to the synthesis of highly
oxygenated triterpenoids. Expression and molecular docking analyses suggest
involvement of specific members of CYP450 family in secondary modifications for
the biosynthesis of bioactive triterpenoids. This study generated rich genomic
resource and identified genes involved in biosynthesis of important molecules,
which will aid in the advancement of tools for functional genomics and
elucidation of the biosynthesis of triterpenoid from this important tree.
PMID- 28698614
TI - Spatial patterns of wet season precipitation vertical gradients on the Tibetan
Plateau and the surroundings.
AB - The Tibetan Plateau and the surrounding (TPS) with its vast land mass and high
elevation affects regional climate and weather. The TPS is also the headwater of
9 major Asian rivers that provide fresh water for 1.65 billion people and many
ecosystems, with wet season (May-September) precipitation being the critical
component of the fresh water. Using station observations, ERA-Interim and MERRA2
reanalysis, we find that wet season precipitation displays vertical gradients
(i.e., changes with elevation) that vary within the region on the TPS. The
decrease of precipitation with elevation occurs in the interior TPS with
elevation larger than 4000 m, little or no change over the southeastern TPS, and
increase elsewhere. The increase of precipitation with elevation is caused by
increasing convective available potential energy (CAPE) and decreasing lifting
condensation level (LCL) with elevation overwhelming the effects of decreasing
total column water vapor (TCWV) with elevation. The decreasing precipitation with
elevation is due to the combined effects of increasing LCL and decreasing TCWV.
LCL and CAPE play a more important role than TCWV in determining the spatial
patterns. These findings are important for hydrology study in observation scarce
mountainous areas, water resources and ecosystem managements in the region.
PMID- 28698615
TI - Influence of the Body Schema on Multisensory Integration: Evidence from the
Mirror Box Illusion.
AB - When placing one hand on each side of a mirror and making synchronous bimanual
movements, the mirror-reflected hand feels like one's own hand that is hidden
behind the mirror. We developed a novel mirror box illusion to investigate
whether motoric, but not spatial, visuomotor congruence is sufficient for
inducing multisensory integration, and importantly, if biomechanical constraints
encoded in the body schema influence multisensory integration. Participants
placed their hands in a mirror box in opposite postures (palm up, palm down),
creating a conflict between visual and proprioceptive feedback for the hand
behind the mirror. After synchronous bimanual hand movements in which the viewed
and felt movements were motorically congruent but spatially in the opposite
direction, participants felt that the hand behind the mirror rotated or
completely flipped towards matching the hand reflection (illusory displacement),
indicating facilitation of multisensory integration by motoric visuomotor
congruence alone. Some wrist rotations are more difficult due to biomechanical
constraints. We predicted that these biomechanical constraints would influence
illusion effectiveness, even though the illusion does not involve actual limb
movement. As predicted, illusory displacement increased as biomechanical
constraints and angular disparity decreased, providing evidence that
biomechanical constraints are processed in multisensory integration.
PMID- 28698616
TI - Barcode ITS2: a useful tool for identifying Trachelospermum jasminoides and a
good monitor for medicine market.
AB - Trachelospermum jasminoides is commonly used in traditional Chinese medicine.
However, the use of the plant's local alternatives is frequent, causing potential
clinical problems. The T. jasminoides sold in the medicine market is commonly
dried and sliced, making traditional identification methods difficult. In this
study, the ITS2 region was evaluated on 127 sequences representing T. jasminoides
and its local alternatives according to PCR and sequencing rates, intra- and
inter-specific divergences, secondary structure, and discrimination capacity.
Results indicated the 100% success rates of PCR and sequencing and the obvious
presence of a barcoding gap. Results of BLAST 1, nearest distance and neighbor
joining tree methods showed that barcode ITS2 could successfully identify all the
texted samples. The secondary structures of the ITS2 region provided another
dimensionality for species identification. Two-dimensional images were obtained
for better and easier identification. Previous studies on DNA barcoding
concentrated more on the same family, genus, or species. However, an ideal
barcode should be variable enough to identify closely related species. Meanwhile,
the barcodes should also be conservative in identifying distantly related
species. This study highlights the application of barcode ITS2 in solving
practical problems in the distantly related local alternatives of medical plants.
PMID- 28698617
TI - Loss of MD1 exacerbates pressure overload-induced left ventricular structural and
electrical remodelling.
AB - Myeloid differentiation protein 1 (MD1) has been implicated in numerous
pathophysiological processes, including immune regulation, obesity, insulin
resistance, and inflammation. However, the role of MD1 in cardiac remodelling
remains incompletely understood. We used MD1-knockout (KO) mice and their wild
type littermates to determine the functional significance of MD1 in the
regulation of aortic banding (AB)-induced left ventricular (LV) structural and
electrical remodelling and its underlying mechanisms. After 4 weeks of AB, MD1-KO
hearts showed substantial aggravation of LV hypertrophy, fibrosis, LV dilation
and dysfunction, and electrical remodelling, which resulted in overt heart
failure and increased electrophysiological instability. Moreover, MD1-KO-AB
cardiomyocytes showed increased diastolic sarcoplasmic reticulum (SR) Ca2+ leak,
reduced Ca2+ transient amplitude and SR Ca2+ content, decreased SR Ca2+-ATPase2
expression, and increased phospholamban and Na+/Ca2+-exchanger 1 protein
expression. Mechanistically, the adverse effects of MD1 deletion on LV
remodelling were related to hyperactivated CaMKII signalling and increased
impairment of intracellular Ca2+ homeostasis, whereas the increased
electrophysiological instability was partly attributed to exaggerated
prolongation of cardiac repolarisation, decreased action potential duration
alternans threshold, and increased diastolic SR Ca2+ leak. Therefore, our study
on MD1 could provide new therapeutic strategies for preventing/treating heart
failure.
PMID- 28698618
TI - An intragenic mutagenesis strategy in Physcomitrella patens to preserve intron
splicing.
AB - Gene targeting is a powerful reverse genetics technique for site-specific genome
modification. Intrinsic homologous recombination in the moss Physcomitrella
patens permits highly effective gene targeting, a characteristic that makes this
organism a valuable model for functional genetics. Functional characterization of
domains located within a multi-domain protein depends on the ability to generate
mutants harboring genetic modifications at internal gene positions while
maintaining the reading-frames of the flanking exons. In this study, we designed
and evaluated different gene targeting constructs for targeted gene manipulation
of sequences corresponding to internal domains of the DEFECTIVE KERNEL1 protein
in Physcomitrella patens. Our results show that gene targeting-associated
mutagenesis of introns can have adverse effects on splicing, corrupting the
normal reading frame of the transcript. We show that successful genetic
modification of internal sequences of multi-exon genes depends on gene-targeting
strategies which insert the selection marker cassette into the 5' end of the
intron and preserve the nucleotide sequence of the targeted intron.
PMID- 28698619
TI - On the stochastic phase stability of Ti2AlC-Cr2AlC.
AB - The quest towards expansion of the M n+1AX n design space has been accelerated
with the recent discovery of several solid solution and ordered phases involving
at least two M n+1AX n end members. Going beyond the nominal M n+1AX n compounds
enables not only fine tuning of existing properties but also entirely new
functionality. This search, however, has been mostly done through painstaking
experiments as knowledge of the phase stability of the relevant systems is rather
scarce. In this work, we report the first attempt to evaluate the finite
temperature pseudo-binary phase diagram of the Ti2AlC-Cr2AlC via first-principles
guided Bayesian CALPHAD framework that accounts for uncertainties not only in ab
initio calculations and thermodynamic models but also in synthesis conditions in
reported experiments. The phase stability analyses are shown to have good
agreement with previous experiments. The work points towards a promising way of
investigating phase stability in other MAX Phase systems providing the knowledge
necessary to elucidate possible synthesis routes for M n+1AX n systems with
unprecedented properties.
PMID- 28698620
TI - Human Platelet Lysate versus Fetal Calf Serum: These Supplements Do Not Select
for Different Mesenchymal Stromal Cells.
AB - Culture medium of mesenchymal stromal cells (MSCs) is usually supplemented with
either human platelet lysate (HPL) or fetal calf serum (FCS). Many studies have
demonstrated that proliferation and cellular morphology are affected by these
supplements - it is therefore important to determine if they favor outgrowth of
different subpopulations and thereby impact on the heterogeneous composition of
MSCs. We have isolated and expanded human bone marrow-derived MSCs in parallel
with HPL or FCS and demonstrated that HPL significantly increases proliferation
and leads to dramatic differences in cellular morphology. Remarkably, global DNA
methylation profiles did not reveal any significant differences. Even at the
transcriptomic level, there were only moderate changes in pairwise comparison.
Furthermore, the effects on proliferation, cytoskeletal organization, and focal
adhesions were reversible by interchanging to opposite culture conditions. These
results indicate that cultivation of MSCs with HPL or FCS has no systematic bias
for specific cell types.
PMID- 28698621
TI - Investigating gene flow between the blind cavefish Garra barreimiae and its
conspecific surface populations.
AB - Cave-dwelling taxa often share the same phenotypic modifications like absence of
eyes and pigmentation. These "troglomorphic characters" are expressed in the
populations of Garra barreimiae from the Al Hoota Cave and nearby Hoti Pit in
Northern Oman. Surface morphotypes of this cyprinid species are common throughout
the distribution area. Very rarely individuals with intermediate phenotypes can
be found. In the present study, potential gene flow between cave and surface
populations was tested and population structure within five sampling sites was
assessed. Overall, 213 individuals were genotyped at 18 microsatellite loci. We
found that the cave populations have lower genetic diversity and are clearly
isolated from the surface populations, which seem to be sporadically in contact
with each other. The results indicate a recent genetic bottleneck in the cave
populations. Thus, it can be assumed that during climatic changes the connection
between cave and surface water bodies was disjoined, leaving a subpopulation
trapped inside. Nevertheless, occasional gene flow between the morphotypes is
detectable, but hybridisation seems only possible in cave habitat with permanent
connection to surface water. Individuals from surface sites bearing intermediate
phenotypes but cave genotypes imply that phenotypic plasticity might play a role
in the development of the phenotype.
PMID- 28698622
TI - Uniaxial orientation of P3HT film prepared by soft friction transfer method.
AB - The realization of room-temperature processes is an important factor in the
development of flexible electronic devices composed of organic materials. In
addition, a simple and cost-effective process is essential to produce stable
working devices and to enhance the performance of a smart material for flexible,
wearable, or stretchable-skin devices. Here, we present a soft friction transfer
method for producing aligned polymer films; a glass substrate was mechanically
brushed with a velvet fabric and poly(3-hexylthiophene) (P3HT) solution was then
spin-coated on the substrate. A P3HT film with a uniaxial orientation was
obtained in air at room temperature. The orientation factor was 17 times higher
than that of a film prepared using a conventional friction transfer technique at
a high temperature of 120 degrees C. In addition, an oriented film with a
thickness of 40 nm was easily picked up and transferred to another substrate. The
mechanism for orientation of the film was investigated using six experimental
methods and theoretical calculation, and was thereby attributed to a chemical
process, i.e., cellulose molecules attach to the substrate and act as a template
for molecular alignment.
PMID- 28698623
TI - Targeted Feature Recognition Using Mechanical Spatial Filtering with a Low-Cost
Compliant Strain Sensor.
AB - A tactile sensing architecture is presented for detection of surface features
that have a particular target size, and the concept is demonstrated with a
braille pattern. The approach is akin to an inverse of mechanical profilometry.
The sensing structure is constructed by suspending a stretchable strain-sensing
membrane over a cavity. The structure is moved over the surface, and a signal is
generated through mechanical spatial filtering if a feature is small enough to
penetrate into the cavity. This simple design is tailorable and can be realized
by standard machining or 3D printing. Images of target features can be produced
with even a low-cost compliant sensor. In this work a disposable elastomeric
piezoresistive strain sensor was used over a cylindrical "finger" part with a
groove having a width corresponding to the braille dot size. A model was
developed to help understand the working principle and guide finger design,
revealing amplification when the cavity matches the feature size. The new sensing
concept has the advantages of being easily reconfigured for a variety of sensing
problems and retrofitted to a wide range of robotic hands, as well as
compatibility with many compliant sensor types.
PMID- 28698624
TI - Naringenin Impairs Two-Pore Channel 2 Activity And Inhibits VEGF-Induced
Angiogenesis.
AB - Our research introduces the natural flavonoid naringenin as a novel inhibitor of
an emerging class of intracellular channels, Two-Pore Channel 2 (TPC2), as shown
by electrophysiological evidence in a heterologous system, i.e. Arabidopsis
vacuoles lacking endogenous TPCs. In view of the control exerted by TPC2 on
intracellular calcium signaling, we demonstrated that naringenin dampens
intracellular calcium responses of human endothelial cells stimulated with VEGF,
histamine or NAADP-AM, but not with ATP or Angiopoietin-1 (negative controls).
The ability of naringenin to impair TPC2-dependent biological activities was
further explored in an established in vivo model, in which VEGF-containing
matrigel plugs implanted in mice failed to be vascularized in the presence of
naringenin. Overall, the present data suggest that naringenin inhibition of TPC2
activity and the observed inhibition of angiogenic response to VEGF are linked by
impaired intracellular calcium signaling. TPC2 inhibition is emerging as a key
therapeutic step in a range of important pathological conditions including the
progression and metastatic potential of melanoma, Parkinson's disease, and Ebola
virus infection. The identification of naringenin as an inhibitor of TPC2
mediated signaling provides a novel and potentially relevant tool for the
advancement of this field of research.
PMID- 28698625
TI - Ectodysplasin target gene Fgf20 regulates mammary bud growth and ductal invasion
and branching during puberty.
AB - Mammary gland development begins with the appearance of epithelial placodes that
invaginate, sprout, and branch to form small arborized trees by birth. The second
phase of ductal growth and branching is driven by the highly invasive structures
called terminal end buds (TEBs) that form at ductal tips at the onset of puberty.
Ectodysplasin (Eda), a tumor necrosis factor-like ligand, is essential for the
development of skin appendages including the breast. In mice, Eda regulates
mammary placode formation and branching morphogenesis, but the underlying
molecular mechanisms are poorly understood. Fibroblast growth factor (Fgf)
receptors have a recognized role in mammary ductal development and stem cell
maintenance, but the ligands involved are ill-defined. Here we report that Fgf20
is expressed in embryonic mammary glands and is regulated by the Eda pathway.
Fgf20 deficiency does not impede mammary gland induction, but compromises mammary
bud growth, as well as TEB formation, ductal outgrowth and branching during
puberty. We further show that loss of Fgf20 delays formation of Eda-induced
supernumerary mammary buds and normalizes the embryonic and postnatal
hyperbranching phenotype of Eda overexpressing mice. These findings identify a
hitherto unknown function for Fgf20 in mammary budding and branching
morphogenesis.
PMID- 28698626
TI - A genome-wide association study suggests the HLA Class II region as the major
susceptibility locus for IgA vasculitis.
AB - The genetic component of Immunoglobulin-A (IgA) vasculitis is still far to be
elucidated. To increase the current knowledge on the genetic component of this
vasculitis we performed the first genome-wide association study (GWAS) on this
condition. 308 IgA vasculitis patients and 1,018 healthy controls from Spain were
genotyped by Illumina HumanCore BeadChips. Imputation of GWAS data was performed
using the 1000 Genomes Project Phase III dataset as reference panel. After
quality control filters and GWAS imputation, 285 patients and 1,006 controls
remained in the datasets and were included in further analysis. Additionally, the
human leukocyte antigen (HLA) region was comprehensively studied by imputing
classical alleles and polymorphic amino acid positions. A linkage disequilibrium
block of polymorphisms located in the HLA class II region surpassed the genome
wide level of significance (OR = 0.56, 95% CI = 0.46-0.68). Although no
polymorphic amino acid positions were associated at the genome-wide level of
significance, P-values of potential relevance were observed for the positions 13
and 11 of HLA-DRB1 (P = 6.67E-05, P = 1.88E-05, respectively). Outside the HLA,
potential associations were detected, but none of them were close to the
statistical significance. In conclusion, our study suggests that IgA vasculitis
is an archetypal HLA class II disease.
PMID- 28698627
TI - The energy disruptor metformin targets mitochondrial integrity via modification
of calcium flux in cancer cells.
AB - Mitochondrial integrity is critical for the regulation of cellular energy and
apoptosis. Metformin is an energy disruptor targeting complex I of the
respiratory chain. We demonstrate that metformin induces endoplasmic reticulum
(ER) stress, calcium release from the ER and subsequent uptake of calcium into
the mitochondria, thus leading to mitochondrial swelling. Metformin triggers the
disorganization of the cristae and inner mitochondrial membrane in several cancer
cells and tumors. Mechanistically, these alterations were found to be due to
calcium entry into the mitochondria, because the swelling induced by metformin
was reversed by the inhibition of mitochondrial calcium uniporter (MCU). We also
demonstrated that metformin inhibits the opening of mPTP and induces
mitochondrial biogenesis. Altogether, the inhibition of mPTP and the increase in
mitochondrial biogenesis may account for the poor pro-apoptotic effect of
metformin in cancer cells.
PMID- 28698628
TI - alphaSynuclein control of mitochondrial homeostasis in human-derived neurons is
disrupted by mutations associated with Parkinson's disease.
AB - The etiology of Parkinson's disease (PD) converges on a common pathogenic pathway
of mitochondrial defects in which alpha-Synuclein (alphaSyn) is thought to play a
role. However, the mechanisms by which alphaSyn and its disease-associated
allelic variants cause mitochondrial dysfunction remain unknown. Here, we
analyzed mitochondrial axonal transport and morphology in human-derived neurons
overexpressing wild-type (WT) alphaSyn or the mutated variants A30P or A53T,
which are known to have differential lipid affinities. A53T alphaSyn was enriched
in mitochondrial fractions, inducing significant mitochondrial transport defects
and fragmentation, while milder defects were elicited by WT and A30P. We found
that alphaSyn-mediated mitochondrial fragmentation was linked to expression
levels in WT and A53T variants. Targeted delivery of WT and A53T alphaSyn to the
outer mitochondrial membrane further increased fragmentation, whereas A30P did
not. Genomic editing to disrupt the N-terminal domain of alphaSyn, which is
important for membrane association, resulted in mitochondrial elongation without
changes in fusion-fission protein levels, suggesting that alphaSyn plays a direct
physiological role in mitochondrial size maintenance. Thus, we demonstrate that
the association of alphaSyn with the mitochondria, which is modulated by protein
mutation and dosage, influences mitochondrial transport and morphology,
highlighting its relevance in a common pathway impaired in PD.
PMID- 28698629
TI - Detecting the presence of fish farm-derived organic matter at the seafloor using
stable isotope analysis of phospholipid fatty acids.
AB - The expansion of global aquaculture activities is important for the wellbeing of
future generations in terms of employment and food security. Rearing animals in
open-exchange cages permits the release of organic wastes, some of which
ultimately reaches the underlying sediments. The development of rapid,
quantitative and objective monitoring techniques is therefore central to the
environmentally sustainable growth of the aquaculture industry. Here, we
demonstrate that fish farm-derived organic wastes can be readily detected at the
seafloor by quantifying sediment phospholipid fatty acids (PLFAs) and their
carbon stable isotope signatures. Observations across five farms reveal that farm
size and/or distance away from it influence the spatial distribution of the
generated organic wastes and their effect on benthic bacterial biomass.
Comparison to the isotopic signatures of fish feed-derived PLFAs indicates that
16:0 and 18:1(n-9) are potential biomarkers for fish farm-derived organic wastes.
Our results suggest that stable isotope analysis of sediment PLFAs has potential
for monitoring the environmental performance of aquaculture activities,
particularly given the increasing prevalence of terrigenous organic matter in
aquaculture feed stocks because it is isotopically district to marine organic
matter.
PMID- 28698630
TI - Electrospray mode transition of microdroplets with semiconductor nanoparticle
suspension.
AB - Electrosprays operate in several modes depending on the flow rate and electric
potential. This allows the deposition of droplets containing nanoparticles into
discrete nanodot arrays to fabricate various electronic devices. In this study,
seven different suspensions with varying properties were investigated. In the
dripping mode, the normalized dropsize decreases linearly with electric capillary
number, Ca e , (ratio of electric to surface tension forces) up to Ca e ~ 1.0.
The effect of viscous forces is found to be negligible in the dripping mode since
the capillary number is small. For flow rates with low Reynolds number, the mode
changes to microdripping mode, and then to a planar oscillating microdripping
mode as Ca e increases. The normalized dropsize remains nearly constant at 0.07
for Ca e > 3.3. The microdripping mode which is important for depositing
discrete array of nanodots is found to occur in the range, 2 <= Ca e <= 2.5. The
droplet frequency increases steadily from dripping to microdripping mode, but
stays roughly constant in the oscillating microdripping mode. This work provides
a physical basis by which the flow rate and the voltage can be chosen for any
nanosuspension to precisely operate in the microdripping mode at a predetermined
dropsize and droplet frequency.
PMID- 28698631
TI - Analytical theory and possible detection of the ac quantum spin Hall effect.
AB - We develop an analytical theory of the low-frequency ac quantum spin Hall (QSH)
effect based upon the scattering matrix formalism. It is shown that the ac QSH
effect can be interpreted as a bulk quantum pumping effect. When the electron
spin is conserved, the integer-quantized ac spin Hall conductivity can be linked
to the winding numbers of the reflection matrices in the electrodes, which also
equal to the bulk spin Chern numbers of the QSH material. Furthermore, a possible
experimental scheme by using ferromagnetic metals as electrodes is proposed to
detect the topological ac spin current by electrical means.
PMID- 28698632
TI - Quality Measurement of Two-dimensional Shear Wave Speed Imaging for Breast
Lesions: the Associated Factors and the Impact to Diagnostic Performance.
AB - This study aimed to identify the associated factors for quality measurement (QM)
of shear wave speed (SWS) imaging and to validate the additional value of QM in
the diagnosis of breast lesions. From September 2014 to February 2015,
conventional ultrasound and SWS imaging were performed in 338 women with 361
breast lesions. Binary logistic regression was used to identify associated
factors for QM. Sensitivity, specificity and the area under receiver operating
characteristic (ROC) curve (AUC) among maximum SWS (SWS max ), QM and SWS max
plus QM (SWS max +QM) were compared to validate additional value of QM. Pathology
confirmed 263 (72.9%) benign lesions and 98 (27.1%) malignancies. Maximum depth
(Odds ratio [OR]: 1.398) and posterior features (OR: 1.206) were identified as
independent associated factors for QM. Compared with SWS max and QM, the
sensitivity of SWS max +QM increased from 67.3%, 64.3% to 83.7% whereas the
specificity decreased from 90.5%, 72.6% to 65.4% (all P < 0.05). SWS max had the
highest AUC in comparison with QM and SWS max +QM (0.849 vs. 0.685 vs. 0.745; P <
0.05). QM for breast lesions is associated with maximum depth and posterior
features. Adding QM to SWS max is useful for breast cancer screening and SWS max
alone is useful for breast cancer differentiation.
PMID- 28698633
TI - A global classification of coastal flood hazard climates associated with large
scale oceanographic forcing.
AB - Coastal communities throughout the world are exposed to numerous and increasing
threats, such as coastal flooding and erosion, saltwater intrusion and wetland
degradation. Here, we present the first global-scale analysis of the main drivers
of coastal flooding due to large-scale oceanographic factors. Given the large
dimensionality of the problem (e.g. spatiotemporal variability in flood magnitude
and the relative influence of waves, tides and surge levels), we have performed a
computer-based classification to identify geographical areas with homogeneous
climates. Results show that 75% of coastal regions around the globe have the
potential for very large flooding events with low probabilities (unbounded
tails), 82% are tide-dominated, and almost 49% are highly susceptible to
increases in flooding frequency due to sea-level rise.
PMID- 28698634
TI - Transportation Safety of Lithium Iron Phosphate Batteries - A Feasibility Study
of Storing at Very Low States of Charge.
AB - In freight classification, lithium-ion batteries are classed as dangerous goods
and are therefore subject to stringent regulations and guidelines for
certification for safe transport. One such guideline is the requirement for
batteries to be at a state of charge of 30%. Under such conditions, a significant
amount of the battery's energy is stored; in the event of mismanagement, or
indeed an airside incident, this energy can lead to ignition and a fire. In this
work, we investigate the effect on the battery of removing 99.1% of the total
stored energy. The performance of 8Ah C6/LiFePO4 pouch cells were measured
following periods of calendar ageing at low voltages, at and well below the
manufacturer's recommended value. Battery degradation was monitored using
impedance spectroscopy and capacity tests; the results show that the cells stored
at 2.3 V exhibited no change in cell capacity after 90 days; resistance rise was
negligible. Energy-dispersive X-ray spectroscopy results indicate that there was
no significant copper dissolution. To test the safety of the batteries at low
voltages, external short-circuit tests were performed on the cells. While the
cells discharged to 2.3 V only exhibited a surface temperature rise of 6 degrees
C, cells at higher voltages exhibited sparks, fumes and fire.
PMID- 28698635
TI - Inhibitory effects of local anesthetics on the proteasome and their biological
actions.
AB - Local anesthetics (LAs) inhibit endoplasmic reticulum-associated protein
degradation, however the mechanisms remain elusive. Here, we show that the
clinically used LAs pilsicainide and lidocaine bind directly to the 20S
proteasome and inhibit its activity. Molecular dynamic calculation indicated that
these LAs were bound to the beta5 subunit of the 20S proteasome, and not to the
other active subunits, beta1 and beta2. Consistently, pilsicainide inhibited only
chymotrypsin-like activity, whereas it did not inhibit the caspase-like and
trypsin-like activities. In addition, we confirmed that the aromatic ring of
these LAs was critical for inhibiting the proteasome. These LAs stabilized p53
and suppressed proliferation of p53-positive but not of p53-negative cancer
cells.
PMID- 28698636
TI - Standardized Nanomechanical Atomic Force Microscopy Procedure (SNAP) for
Measuring Soft and Biological Samples.
AB - We present a procedure that allows a reliable determination of the elastic
(Young's) modulus of soft samples, including living cells, by atomic force
microscopy (AFM). The standardized nanomechanical AFM procedure (SNAP) ensures
the precise adjustment of the AFM optical lever system, a prerequisite for all
kinds of force spectroscopy methods, to obtain reliable values independent of the
instrument, laboratory and operator. Measurements of soft hydrogel samples with a
well-defined elastic modulus using different AFMs revealed that the uncertainties
in the determination of the deflection sensitivity and subsequently cantilever's
spring constant were the main sources of error. SNAP eliminates those errors by
calculating the correct deflection sensitivity based on spring constants
determined with a vibrometer. The procedure was validated within a large network
of European laboratories by measuring the elastic properties of gels and living
cells, showing that its application reduces the variability in elastic moduli of
hydrogels down to 1%, and increased the consistency of living cells elasticity
measurements by a factor of two. The high reproducibility of elasticity
measurements provided by SNAP could improve significantly the applicability of
cell mechanics as a quantitative marker to discriminate between cell types and
conditions.
PMID- 28698637
TI - Distinct Properties of Long-Term Potentiation in the Dentate Gyrus along the
Dorsoventral Axis: Influence of Age and Inhibition.
AB - The hippocampus is important for spatial navigation, episodic memory and
affective behaviour. Increasing evidence suggests that these multiple functions
are accomplished by different segments along the dorsal-ventral (septal-temporal)
axis. Long-term potentiation (LTP), the best-investigated cellular correlate of
learning and memory, has distinct properties along this axis in the CA1 region,
but so far, little is known about longitudinal differences in dentate gyrus (DG).
Therefore, here we examined potential dorsoventral differences in DG-LTP using in
vitro multi-electrode array recordings. In young mice, we found higher basal
synaptic transmission in the dorsal DG, while the LTP magnitude markedly
increased towards the ventral pole. Strikingly, these differences were greatly
reduced in slices from middle-aged mice. Short-term plasticity, evaluated by
paired-pulse ratios, was similar across groups. Recordings in the presence and
absence of GABAA-receptor blocker picrotoxin suggested a higher inhibitory tone
in the ventral DG of young mice, confirmed by an increased frequency of miniature
inhibitory postsynaptic currents. Our findings support the view that the
hippocampus contains discrete functional domains along its dorsoventral axis and
demonstrate that these are subject to age-dependent changes. Since these
characteristics are presumably conserved in the human hippocampus, our findings
have important clinical implications for hippocampus- and age-related disorders.
PMID- 28698638
TI - Sustainable Electrochemical Depolymerization of Lignin in Reusable Ionic Liquids.
AB - Lignin's aromatic building blocks provide a chemical resource that is, in theory,
ideal for substitution of aromatic petrochemicals. Moreover, degradation and
valorization of lignin has the potential to generate many high-value chemicals
for technical applications. In this study, electrochemical degradation of alkali
and Organosolv lignin was performed using the ionic liquids 1-ethyl-3
methylimidazolium trifluoromethanesulfonate and triethylammonium
methanesulfonate. The extensive degradation of the investigated lignins with
simultaneous almost full recovery of the electrolyte materials provided a
sustainable alternative to more common lignin degradation processes. We
demonstrate here that both the presence (and the absence) of water during
electrolysis and proton transport reactions had significant impact on the
degradation efficiency. Hydrogen peroxide radical formation promoted certain
electrochemical mechanisms in electrolyte systems "contaminated" with water and
increased yields of low molecular weight products significantly. The proposed
mechanisms were tentatively confirmed by determining product distributions using
a combination of liquid chromatography-mass spectrometry and gas-chromatography
mass spectrometry, allowing measurement of both polar versus non-polar as well as
volatile versus non-volatile components in the mixtures.
PMID- 28698639
TI - Optimization of hormone combinations for root growth and bud germination in
Chinese fir (Cunninghamia lanceolata) clone leaf cuttings.
AB - In order to ascertain the optimal hormone combination for Chinese fir
(Cunninghamia lanceolata) leaf cuttings, an L16(4)4 orthogonal test of 6
benzylaminopurine (6-BA), 1-naphthaleneacetic acid (NAA), and indole-3-butyric
acid (IBA) (0, 10, 30, or 50 mg . L-1 of each exogenous hormone) immersion for 5,
10, 15, or 20 min was conducted. Callus initiation rate and rooting promotion
rate were mainly affected by treatment time, root length increase by 6-BA
concentration, and bud germination rate and plantlet formation rate by NAA
concentration. The expected optimal combination for callus initiation rate was 50
mg . L-1 6-BA + 0 mg . L-1 NAA + 30 mg . L-1 IBA + 10 min; for rooting promotion
rate, it was 0-10 mg . L-1 6-BA + 10 mg . L-1 NAA + 30 mg . L-1 IBA + 20 min; for
bud germination rate, it was 50 mg . L-1 6-BA + 0-10 mg . L-1 NAA + 0-30 mg . L-1
IBA + 20 min; and for seedling formation rate for No. 4, it was 10 mg . L-1 6-BA
+ 10 mg . L-1 NAA + 0 mg . L-1 IBA + 20 min. Light microscopy image analysis
revealed that a cluster of primordial cells was produced 40 days after cutting,
and mastoid cells developed into peninsula cells in calli that were cultured for
50 days.
PMID- 28698640
TI - Enhancement of carrier transport characteristic in the Sb2Se2Te topological
insulators by N2 adsorption.
AB - The carrier transport characteristics of Sb2Se2Te topological insulators were
investigated, after exposure to different levels of nitrogen gas. The
magnetoresistance (MR) slope for the Sb2Se2Te crystal increased by approximately
100% at 10 K after 2-days of exposure. The Shubnikov-de Haas (SdH) oscillation
amplitude increased by 30% while oscillation frequencies remained the same. MR
slopes and the mobilities had the same dependency on temperature over a wide
temperature range. All measured data conformed to a linear correlation between MR
slope and mobility, supporting our hypothesis that the MR increase and the SdH
oscillation enhancement might be caused by mobility enhancement induced by
adsorbed N2 molecular.
PMID- 28698641
TI - A Transcription Activator-Like Effector Tal7 of Xanthomonas oryzae pv. oryzicola
Activates Rice Gene Os09g29100 to Suppress Rice Immunity.
AB - Xanthomonas oryzae pv. oryzicola (Xoc) and X. oryzae pv. oryzae (Xoo) cause
bacterial leaf streak (BLS) and bacterial leaf blight (BLB) in rice,
respectively. Unlike Xoo, endogenous avirulence-resistance (avr-R) gene
interactions have not been identified in the Xoc-rice pathosystem; however, both
pathogens possess transcription activator-like effectors (TALEs) that are known
to modulate R or S genes in rice. The transfer of individual tal genes from Xoc
RS105 (hypervirulent) into Xoc YNB0-17 (hypovirulent) led to the identification
of tal7, which suppressed avrXa7-Xa7 mediated defense in rice containing an Xa7 R
gene. Mobility shift and microscale thermophoresis assays showed that Tal7 bound
two EBE sites in the promoters of two rice genes, Os09g29100 and Os12g42970,
which encode predicted Cyclin-D4-1 and GATA zinc finger family protein,
respectively. Assays using designer TALEs and a TALE-free strain of Xoo revealed
that Os09g29100 was the biologically relevant target of Tal7. Tal7 activates the
expression of rice gene Os09g29100 that suppresses avrXa7-Xa7 mediated defense in
Rice. TALEN editing of the Tal7-binding site in the Os09g29100 gene promoter
further enhanced resistance to the pathogen Xoc RS105. The suppression of
effector-trigger immunity (ETI) is a phenomenon that may contribute to the
scarcity of BLS resistant cultivars.
PMID- 28698642
TI - Progressive Changes in CXCR4 Expression That Define Thymocyte Positive Selection
Are Dispensable For Both Innate and Conventional alphabetaT-cell Development.
AB - The ordered migration of immature thymocytes through thymic microenvironments
generates both adaptive MHC restricted alphabetaT-cells and innate CD1d
restricted iNKT-cells. While several chemokine receptors and ligands control
multiple stages of this process, their involvement during early thymocyte
development often precludes direct analysis of potential roles during later
developmental stages. For example, because of early lethality of CXCR4-/- mice,
and stage-specific requirements for CXCR4 in thymus colonisation and pre-TCR
mediated selection, its role in thymic positive selection is unclear. Here we
have examined CXCR4-CXCL12 interactions during the maturation of CD4+CD8+
thymocytes, including downstream stages of iNKT and alphabetaT-cell development.
We show CXCL12 expression is a common feature of cortical thymic epithelial
cells, indicating widespread availability throughout the cortex. Moreover, CXCR4
expression by CD4+CD8+ pre-selection thymocytes is progressively downregulated
following both MHC and CD1d-restricted thymic selection events. However, using
CD4Cre-mediated deletion to bypass its involvement in CD4-CD8- thymocyte
development, we show CXCR4 is dispensable for the maintenance and intrathymic
positioning of CD4+CD8+ thymocytes, and their ability to generate mature
alphabetaT-cells and CD1d-restricted iNKT-cells. Collectively, our data define
dynamic changes in CXCR4 expression as a marker for intrathymic selection events,
and show its role in T-cell development is restricted to pre-CD4+CD8+ stages.
PMID- 28698643
TI - Effects of gratitude meditation on neural network functional connectivity and
brain-heart coupling.
AB - A sense of gratitude is a powerful and positive experience that can promote a
happier life, whereas resentment is associated with life dissatisfaction. To
explore the effects of gratitude and resentment on mental well-being, we acquired
functional magnetic resonance imaging and heart rate (HR) data before, during,
and after the gratitude and resentment interventions. Functional connectivity
(FC) analysis was conducted to identify the modulatory effects of gratitude on
the default mode, emotion, and reward-motivation networks. The average HR was
significantly lower during the gratitude intervention than during the resentment
intervention. Temporostriatal FC showed a positive correlation with HR during the
gratitude intervention, but not during the resentment intervention.
Temporostriatal resting-state FC was significantly decreased after the gratitude
intervention compared to the resentment intervention. After the gratitude
intervention, resting-state FC of the amygdala with the right dorsomedial
prefrontal cortex and left dorsal anterior cingulate cortex were positively
correlated with anxiety scale and depression scale, respectively. Taken together,
our findings shed light on the effect of gratitude meditation on an individual's
mental well-being, and indicate that it may be a means of improving both emotion
regulation and self-motivation by modulating resting-state FC in emotion and
motivation-related brain regions.
PMID- 28698644
TI - Cognitive performance in healthy older adults relates to spontaneous switching
between states of functional connectivity during rest.
AB - Growing evidence has shown that brain activity at rest slowly wanders through a
repertoire of different states, where whole-brain functional connectivity (FC)
temporarily settles into distinct FC patterns. Nevertheless, the functional role
of resting-state activity remains unclear. Here, we investigate how the switching
behavior of resting-state FC relates with cognitive performance in healthy older
adults. We analyse resting-state fMRI data from 98 healthy adults previously
categorized as being among the best or among the worst performers in a cohort
study of >1000 subjects aged 50+ who underwent neuropsychological assessment. We
use a novel approach focusing on the dominant FC pattern captured by the leading
eigenvector of dynamic FC matrices. Recurrent FC patterns - or states - are
detected and characterized in terms of lifetime, probability of occurrence and
switching profiles. We find that poorer cognitive performance is associated with
weaker FC temporal similarity together with altered switching between FC states.
These results provide new evidence linking the switching dynamics of FC during
rest with cognitive performance in later life, reinforcing the functional role of
resting-state activity for effective cognitive processing.
PMID- 28698645
TI - Heart rhythm characterization through induced physiological variables.
AB - Atrial fibrillation remains a major cause of morbi-mortality, making mass
screening desirable and leading industry to actively develop devices devoted to
automatic AF detection. Because there is a tendency toward mobile devices, there
is a need for an accurate, rapid method for studying short inter-beat interval
time series for real-time automatic medical monitoring. We report a new
methodology to efficiently select highly discriminative variables between
physiological states, here a normal sinus rhythm or atrial fibrillation. We
generate induced variables using the first ten time derivatives of an RR interval
time series and formally express a new multivariate metric quantifying their
discriminative power to drive state variable selection. When combined with a
simple classifier, this new methodology results in 99.9% classification accuracy
for 1-min RR interval time series (n = 7,400), with heart rate accelerations and
jerks being the most discriminant variables. We show that the RR interval time
series can be drastically reduced from 60 s to 3 s, with a classification
accuracy of 95.0%. We show that heart rhythm characterization is facilitated by
induced variables using time derivatives, which is a generic methodology that is
particularly suitable to real-time medical monitoring.
PMID- 28698646
TI - Plasma biomarkers are associated with agitation and regional brain atrophy in
Alzheimer's disease.
AB - This study investigated the relationships among plasma biomarkers, regional brain
atrophy, and clinical symptoms in patients with Alzheimer's disease (AD; n =
177), mild cognitive impairment (MCI; N = 60) and controls (n = 108). The Mini
Mental Status Examination (MMSE), Clinical Dementia Rating (CDR), and
Neuropsychiatric Inventory (NPI) subscales were administered to subjects.
Magnetic resonance imaging was performed and medial temporal atrophy (MTA) and
posterior atrophy (PA) were assessed visually. We examined associations among
cognition, NPI score, plasma beta-amyloid (Abeta) and clusterin levels, and
regional brain atrophy in patients with AD by regression analysis. The mean MTA
score was associated with the plasma Abeta1-42/Abeta1-40 ratio (r = 0.38, p =
0.01) and with MMSE scores (r = 0.43, p < 0.01). The plasma clusterin level was
correlated with CDR sum of box and right-side PA scores (r = 0.28, p = 0.01 and r
= 0.30, p = 0.03, respectively). Right-side PA scores were correlated
significantly with NPI agitation/aggression (r = 0.30, p = 0.03) subscale scores.
In conclusion, the plasma ratio of Abeta1-42/Abeta1-40 and clusterin level may be
associated with different patterns of regional brain atrophy, which in turn may
account for the clinical symptoms in patients with AD.
PMID- 28698647
TI - Identification of FBXL4 as a Metastasis Associated Gene in Prostate Cancer.
AB - Prostate cancer is the most common cancer among western men, with a significant
mortality and morbidity reported for advanced metastatic disease. Current
understanding of metastatic disease is limited due to difficulty of sampling as
prostate cancer mainly metastasizes to bone. By analysing prostate cancer bone
metastases using high density microarrays, we found a common genomic copy number
loss at 6q16.1-16.2, containing the FBXL4 gene, which was confirmed in larger
series of bone metastases by fluorescence in situ hybridisation (FISH). Loss of
FBXL4 was also detected in primary tumours and it was highly associated with
prognostic factors including high Gleason score, clinical stage, prostate
specific antigen (PSA) and extent of disease, as well as poor patient survival,
suggesting that FBXL4 loss contributes to prostate cancer progression. We also
demonstrated that FBXL4 deletion is detectable in circulating tumour cells
(CTCs), making it a potential prognostic biomarker by 'liquid biopsy'. In vitro
analysis showed that FBXL4 plays a role in regulating the migration and invasion
of prostate cancer cells. FBXL4 potentially controls cancer metastasis through
regulation of ERLEC1 levels. Therefore, FBXL4 could be a potential novel prostate
cancer suppressor gene, which may prevent cancer progression and metastasis
through controlling cell invasion.
PMID- 28698648
TI - In-situ terahertz optical Hall effect measurements of ambient effects on free
charge carrier properties of epitaxial graphene.
AB - Unraveling the doping-related charge carrier scattering mechanisms in two
dimensional materials such as graphene is vital for limiting parasitic electrical
conductivity losses in future electronic applications. While electric field
doping is well understood, assessment of mobility and density as a function of
chemical doping remained a challenge thus far. In this work, we investigate the
effects of cyclically exposing epitaxial graphene to controlled inert gases and
ambient humidity conditions, while measuring the Lorentz force-induced
birefringence in graphene at Terahertz frequencies in magnetic fields. This
technique, previously identified as the optical analogue of the electrical Hall
effect, permits here measurement of charge carrier type, density, and mobility in
epitaxial graphene on silicon-face silicon carbide. We observe a distinct, nearly
linear relationship between mobility and electron charge density, similar to
field-effect induced changes measured in electrical Hall bar devices previously.
The observed doping process is completely reversible and independent of the type
of inert gas exposure.
PMID- 28698649
TI - Characterizing the scent and chemical composition of Panthera leo marking fluid
using solid-phase microextraction and multidimensional gas chromatography-mass
spectrometry-olfactometry.
AB - Lions (Panthera leo) use chemical signaling to indicate health, reproductive
status, and territorial ownership. To date, no study has reported on both scent
and composition of marking fluid (MF) from P. leo. The objectives of this study
were to: 1) develop a novel method for simultaneous chemical and scent
identification of lion MF in its totality (urine + MF), 2) identify
characteristic odorants responsible for the overall scent of MF as perceived by
human panelists, and 3) compare the existing library of known odorous compounds
characterized as eliciting behaviors in animals in order to understand potential
functionality in lion behavior. Solid-phase microextraction and simultaneous
chemical-sensory analyses with multidimensional gas-chromatography-mass
spectrometry-olfactometry improved separating, isolating, and identifying mixed
(MF, urine) compounds versus solvent-based extraction and chemical analyses. 2,5
Dimethylpyrazine, 4-methylphenol, and 3-methylcyclopentanone were isolated and
identified as the compounds responsible for the characteristic odor of lion MF.
Twenty-eight volatile organic compounds (VOCs) emitted from MF were identified,
adding a new list of compounds previously unidentified in lion urine. New
chemicals were identified in nine compound groups: ketones, aldehydes, amines,
alcohols, aromatics, sulfur-containing compounds, phenyls, phenols, and volatile
fatty acids. Twenty-three VOCs are known semiochemicals that are implicated in
attraction, reproduction, and alarm-signaling behaviors in other species.
PMID- 28698650
TI - Complementary Role of Fibroblast Growth Factor 21 and Cytokeratin 18 in
Monitoring the Different Stages of Nonalcoholic Fatty Liver Disease.
AB - Fibroblast growth factor 21 (FGF21) and cytokeratin 18 (CK18) were previously
reported to be elevated in nonalcoholic fatty liver disease (NAFLD). We aim to
analyze the differential roles of FGF21, cell apoptosis marker CK18 fragment M30
and total cell death marker CK18 M65ED in monitoring the different stages of
NAFLD spectrum in a population-based prospective cohort comprising 808 Chinese
subjects. Predictive performances for monitoring the different stages of NAFLD
were assessed by logistic regression and receiver-operating characteristic (ROC)
curves. We found baseline FGF21 but not CK18 level was an independent predictor
for the development of simple steatosis. NAFLD patients who had remission during
follow-up had significantly lower baseline M30 levels than those who sustained
NAFLD (84.74U/L [53.26-135.79] vs. 118.47U/L [87.16-188.89], P = 0.012). M65ED
was independently predictive of progressing to suspected non-alcoholic
steatohepatitis (NASH) in NAFLD patients. These results suggest that FGF21 can be
used for early identification of hepatic steatosis. On the other hand, CK18
including M30 and M65ED, are predictive of the prognosis of NAFLD patients. FGF21
and CK18 might play differential roles and have complementary value in non
invasive identification and monitoring the outcome of NAFLD patients.
PMID- 28698651
TI - Ion Concentration Polarization by Bifurcated Current Path.
AB - Ion concentration polarization (ICP) is a fundamental electrokinetic process that
occurs near a perm-selective membrane under dc bias. Overall process highly
depends on the current transportation mechanisms such as electro-convection,
surface conduction and diffusioosmosis and the fundamental characteristics can be
significantly altered by external parameters, once the permselectivity was fixed.
In this work, a new ICP device with a bifurcated current path as for the
enhancement of the surface conduction was fabricated using a polymeric nanoporous
material. It was protruded to the middle of a microchannel, while the material
was exactly aligned at the interface between two microchannels in a conventional
ICP device. Rigorous experiments revealed out that the propagation of ICP layer
was initiated from the different locations of the protruded membrane according to
the dominant current path which was determined by a bulk electrolyte
concentration. Since the enhancement of surface conduction maintained the
stability of ICP process, a strong electrokinetic flow associated with the
amplified electric field inside ICP layer was significantly suppressed over the
protruded membrane even at condensed limit. As a practical example of utilizing
the protruded device, we successfully demonstrated a non-destructive
micro/nanofluidic preconcentrator of fragile cellular species (i.e. red blood
cells).
PMID- 28698652
TI - Electrical properties of graphene-metal contacts.
AB - The performance of devices and systems based on two-dimensional material systems
depends critically on the quality of the contacts between 2D material and metal.
A low contact resistance is an imperative requirement to consider graphene as a
candidate material for electronic and optoelectronic devices. Unfortunately,
measurements of contact resistance in the literature do not provide a consistent
picture, due to limitations of current graphene technology, and to incomplete
understanding of influencing factors. Here we show that the contact resistance is
intrinsically dependent on graphene sheet resistance and on the chemistry of the
graphene-metal interface. We present a physical model of the contacts based on ab
initio simulations and extensive experiments carried out on a large variety of
samples with different graphene-metal contacts. Our model explains the spread in
experimental results as due to uncontrolled graphene doping and suggests ways to
engineer contact resistance. We also predict an achievable contact resistance of
30 Omega.MUm for nickel electrodes, extremely promising for applications.
PMID- 28698654
TI - Megapixel multi-elemental imaging by Laser-Induced Breakdown Spectroscopy, a
technology with considerable potential for paleoclimate studies.
AB - Paleoclimate studies play a crucial role in understanding past and future
climates and their environmental impacts. Current methodologies for performing
highly sensitive elemental analysis at micrometre spatial resolutions are
restricted to the use of complex and/or not easily applied techniques, such as
synchrotron radiation X-ray fluorescence micro-analysis (MU-SRXRF), nano
secondary ion mass spectrometry (nano-SIMS) or laser ablation inductively coupled
plasma mass spectrometry (LA-ICP-MS). Moreover, the analysis of large samples
(>few cm2) with any of these methods remains very challenging due to their
relatively low acquisition speed (~1-10 Hz), and because they must be operated in
vacuum or controlled atmosphere. In this work, we proposed an imaging methodology
based on laser-induced breakdown spectroscopy, to perform fast multi-elemental
scanning of large geological samples with high performance in terms of
sensitivity (ppm-level), lateral resolution (up to 10 MUm) and operating speed
(100 Hz). This method was successfully applied to obtain the first megapixel
images of large geological samples and yielded new information, not accessible
using other techniques. These results open a new perspective into the use of
laser spectroscopy in a variety of geochemical applications.
PMID- 28698653
TI - The Association between High Fat Diet around Gestation and Metabolic Syndrome
related Phenotypes in Rats: A Systematic Review and Meta-Analysis.
AB - Numerous rodent studies have evaluated the effects of a maternal high-fat diet
(HFD) on later in life susceptibility to Metabolic Syndrome (MetS) with varying
results. Our aim was to quantitatively synthesize the available data on effects
of maternal HFD around gestation on offspring's body mass, body fat, plasma
leptin, glucose, insulin, lipids and systolic blood pressure (SBP). Literature
was screened and summary estimates of the effect of maternal HFD on outcomes were
calculated by using fixed- or random-effects models. 362 effect sizes from 68
studies together with relevant moderators were collected. We found that maternal
HFD is statistically associated with higher body fat, body weight, leptin,
glucose, insulin and triglycerides levels, together with increased SBP in
offspring later in life. Our analysis also revealed non-significant overall
effect on offspring's HDL-cholesterol. A main source of variation among studies
emerged from rat strain and lard-based diet type. Strain and sex -specific
effects on particular data subsets were detected. Recommendations are suggested
for future research in the field of developmental programming of the MetS.
Despite significant heterogeneity, our meta-analysis confirms that maternal HFD
had long-term metabolic effects in offspring.
PMID- 28698655
TI - Electronic bandstructure and van der Waals coupling of ReSe2 revealed by high
resolution angle-resolved photoemission spectroscopy.
AB - ReSe2 and ReS2 are unusual compounds amongst the layered transition metal
dichalcogenides as a result of their low symmetry, with a characteristic in-plane
anisotropy due to in-plane rhenium 'chains'. They preserve inversion symmetry
independent of the number of layers and, in contrast to more well-known
transition metal dichalcogenides, bulk and few-monolayer Re-TMD compounds have
been proposed to behave as electronically and vibrational decoupled layers. Here,
we probe for the first time the electronic band structure of bulk ReSe2 by direct
nanoscale angle-resolved photoemission spectroscopy. We find a highly anisotropic
in- and out-of-plane electronic structure, with the valence band maxima located
away from any particular high-symmetry direction. The effective mass doubles its
value perpendicular to the Re chains and the interlayer van der Waals coupling
generates significant electronic dispersion normal to the layers. Our density
functional theory calculations, including spin-orbit effects, are in excellent
agreement with these experimental findings.
PMID- 28698656
TI - Gene-gene and gene-environment interactions influence platinum-based chemotherapy
response and toxicity in non-small cell lung cancer patients.
AB - Platinum-based chemotherapy is a major therapeutic regimen of lung cancer.
Various single nucleotide polymorphisms (SNPs) reported were associated with
platinum-based chemotherapy response and drug toxicity. However, neither of the
studies explored this association from SNP-SNP interaction perspective nor taking
into effects of SNP-environment consideration simultaneously. We genotyped 504
polymorphisms and explore the association of gene-gene and gene-environment
interactions with platinum-based chemotherapy response and toxicity in 490 NSCLC
patients. 16 SNPs were found significantly associated with platinum-based
chemotherapy, and they were picked out as study object in the validation cohort.
We recruited 788 patients in the validation cohort. We found that HSPD1
rs17730989-SUMF1 rs2633851 interaction was associated with platinum-based
chemotherapy-induced hematologic toxicity (adjusted OR = 0.233, P = 0.018). In
addition, the combined effect of ABCG2 rs2231142-CES5A rs3859104 was
significantly associated with overall toxicity (adjusted OR = 8.044, P = 4.350 *
10-5). Besides, the model of ARHGAP26 rs3776332-ERCC6 rs2228528-SLC2A1 rs4658
histology was associated with platinum-based chemotherapeutic response. Gene-gene
and gene-environment interactions have been identified to contribute to
chemotherapy sensitivity and toxicity. They can potentially predict drug response
and toxicity of platinum-based chemotherapy in NSCLC patients.
PMID- 28698657
TI - Anaerobic oxidation of methane coupled with extracellular electron transfer to
electrodes.
AB - Anaerobic oxidation of methane (AOM) is an important process for understanding
the global flux of methane and its relation to the global carbon cycle. Although
AOM is known to be coupled to reductions of sulfate, nitrite, and nitrate,
evidence that AOM is coupled with extracellular electron transfer (EET) to
conductive solids is relatively insufficient. Here, we demonstrate EET-dependent
AOM in a biofilm anode dominated by Geobacter spp. and Methanobacterium spp.
using carbon-fiber electrodes as the terminal electron sink. The steady-state
current density was kept at 11.0 +/- 1.3 mA/m2 in a microbial electrochemical
cell, and isotopic experiments supported AOM-EET to the anode. Fluorescence in
situ hybridization images and metagenome results suggest that Methanobacterium
spp. may work synergistically with Geobacter spp. to allow AOM, likely by
employing intermediate (formate or H2)-dependent inter-species electron
transport. Since metal oxides are widely present in sedimentary and terrestrial
environments, an AOM-EET niche would have implications for minimizing the net
global emissions of methane.
PMID- 28698658
TI - Intercellular adhesion molecule-1 augments myoblast adhesion and fusion through
homophilic trans-interactions.
AB - The overall objective of the study was to identify mechanisms through which
intercellular adhesion molecule-1 (ICAM-1) augments the adhesive and fusogenic
properties of myogenic cells. Hypotheses were tested using cultured myoblasts and
fibroblasts, which do not constitutively express ICAM-1, and myoblasts and
fibroblasts forced to express full length ICAM-1 or a truncated form lacking the
cytoplasmic domain of ICAM-1. ICAM-1 mediated myoblast adhesion and fusion were
quantified using novel assays and cell mixing experiments. We report that ICAM-1
augments myoblast adhesion to myoblasts and myotubes through homophilic trans
interactions. Such adhesive interactions enhanced levels of active Rac in
adherent and fusing myoblasts, as well as triggered lamellipodia, spreading, and
fusion of myoblasts through the signaling function of the cytoplasmic domain of
ICAM-1. Rac inhibition negated ICAM-1 mediated lamellipodia, spreading, and
fusion of myoblasts. The fusogenic property of ICAM-1-ICAM-1 interactions was
restricted to myogenic cells, as forced expression of ICAM-1 by fibroblasts did
not augment their fusion to ICAM-1+ myoblasts/myotubes. We conclude that ICAM-1
augments myoblast adhesion and fusion through its ability to self-associate and
initiate Rac-mediated remodeling of the actin cytoskeleton.
PMID- 28698659
TI - Abrupt emergence of a large pockmark field in the German Bight, southeastern
North Sea.
AB - A series of multibeam bathymetry surveys revealed the emergence of a large
pockmark field in the southeastern North Sea. Covering an area of around 915 km2,
up to 1,200 pockmarks per square kilometer have been identified. The time of
emergence can be confined to 3 months in autumn 2015, suggesting a very dynamic
genesis. The gas source and the trigger for the simultaneous outbreak remain
speculative. Subseafloor structures and high methane concentrations of up to 30
MUmol/l in sediment pore water samples suggest a source of shallow biogenic
methane from the decomposition of postglacial deposits in a paleo river valley.
Storm waves are suggested as the final trigger for the eruption of the gas. Due
to the shallow water depths and energetic conditions at the presumed time of
eruption, a large fraction of the released gas must have been emitted to the
atmosphere. Conservative estimates amount to 5 kt of methane, equivalent to 67%
of the annual release from the entire North Sea. These observations most probably
describe a reoccurring phenomenon in shallow shelf seas, which may have been
overlooked before because of the transient nature of shallow water bedforms and
technology limitations of high resolution bathymetric mapping.
PMID- 28698660
TI - Hydrogen sulfide acts as a double-edged sword in human hepatocellular carcinoma
cells through EGFR/ERK/MMP-2 and PTEN/AKT signaling pathways.
AB - Hydrogen sulfide (H2S) is involved in cancer biological processes. However, there
are several controversies concerning the role of H2S in cancer development and
progression. In this study, we found that the growth and migration of
hepatocellular carcinoma (HCC) cells were enhanced by 10-100 MUM NaHS and dose
dependently inhibited by 600-1000 MUM NaHS. The apoptotic levels were reduced by
25-100 MUM NaHS but increased by 400-1000 MUM NaHS in HCC cells. After treatment
with 25-50 MUM NaHS, the protein levels of p-EGFR, p-ERK, MMP-2, and p-AKT were
increased, whereas the levels of PTEN and the ratio of BAX/BCL-2 were down
regulated. Administration of 800-1000 MUM NaHS showed opposite effects on these
protein levels in HCC cells. However, H2S showed no effects on the growth,
migration, apoptosis, and the protein levels of the EGFR/ERK/MMP-2 and PTEN/AKT
signaling pathways in L02 cells. Furthermore, 25-100 MUM NaHS promoted HCC tumor
growth and blood vessel formation, while 800-1000 MUM NaHS inhibited angiogenesis
and tumor growth with no obvious systemic toxicity. These results indicate that
H2S acts as a double-edged sword in HCC cells through EGFR/ERK/MMP-2 and PTEN/AKT
signaling pathways. Novel H2S donors could be designed and applied for further
antitumor research.
PMID- 28698661
TI - The non-bilayer lipid MGDG stabilizes the major light-harvesting complex (LHCII)
against unfolding.
AB - In the photosynthetic apparatus of plants a high proportion of LHCII protein is
needed to integrate 50% non-bilayer lipid MGDG into the lamellar thylakoid
membrane, but whether and how the stability of the protein is also affected is
not known. Here we use single-molecule force spectroscopy to map the stability of
LHCII against mechanical unfolding along the polypeptide chain as a function of
oligomerization state and lipid composition. Comparing unfolding forces between
monomeric and trimeric LHCII demonstrates that the stability does not increase
significantly upon trimerization but can mainly be correlated with specific
contact sites between adjacent monomers. In contrast, unfolding of trimeric
complexes in membranes composed of different thylakoid lipids reveals that the
non-bilayer lipid MGDG substantially increases the mechanical stability of LHCII
in many segments of the protein compared to other lipids such as DGDG or POPG. We
attribute these findings to steric matching of conically formed MGDG and the
hourglass shape of trimeric LHCII, thereby extending the role of non-bilayer
lipids to the structural stabilization of membrane proteins in addition to the
modulation of their folding, conformation and function.
PMID- 28698664
TI - Regenerative medicine: Bioengineering the common bile duct.
PMID- 28698662
TI - The extracellular matrix of the gastrointestinal tract: a regenerative medicine
platform.
AB - The synthesis and secretion of components that constitute the extracellular
matrix (ECM) by resident cell types occur at the earliest stages of embryonic
development, and continue throughout life in both healthy and diseased
physiological states. The ECM consists of a complex mixture of insoluble and
soluble functional components that are arranged in a tissue-specific 3D
ultrastructure, and it regulates numerous biological processes, including
angiogenesis, innervation and stem cell differentiation. Owing to its composition
and influence on embryonic development, as well as cellular and organ
homeostasis, the ECM is an ideal therapeutic substrate for the repair of damaged
or diseased tissues. Biologic scaffold materials that are composed of ECM have
been used in various surgical and tissue-engineering applications. The
gastrointestinal (GI) tract presents distinct challenges, such as diverse pH
conditions and the requirement for motility and nutrient absorption. Despite
these challenges, the use of homologous and heterologous ECM bioscaffolds for the
focal or segmental reconstruction and regeneration of GI tissue has shown promise
in early preclinical and clinical studies. This Review discusses the importance
of tissue-specific ECM bioscaffolds and highlights the major advances that have
been made in regenerative medicine strategies for the reconstruction of
functional GI tissues.
PMID- 28698663
TI - Medical devices for the treatment of obesity.
AB - Obesity is a major public health concern that leads to numerous metabolic,
mechanical and psychological complications. Although lifestyle interventions are
the cornerstone of obesity management, subsequent physiological neurohormonal
adaptations limit weight loss, strongly favour weight regain and counteract
sustained weight loss. A range of effective therapies are therefore needed to
manage this chronic relapsing disease. Bariatric surgery delivers substantial,
durable weight loss but limited access to care, perceived high risks and costs
restrict uptake. Medical devices are uniquely positioned to bridge the gap
between more conservative lifestyle intervention and weight-loss pharmacotherapy
and more disruptive bariatric surgery. In this Review, we examine the range of
gastrointestinal medical devices that are available in clinical practice to treat
obesity, as well as those that are in advanced stages of development. We focus on
the mechanisms of action as well as the efficacy and safety profiles of these
devices. Many of these devices are placed endoscopically, which provides
gastroenterologists with exciting opportunities for treatment.
PMID- 28698665
TI - Antigens Rv0310c and Rv1255c are promising novel biomarkers for the diagnosis of
Mycobacterium tuberculosis infection.
AB - This study aimed to identify novel immunogenic epitopes from Mycobacterium
tuberculosis (MTB) that could be used in tuberculosis (TB) diagnostics. To
determine the diagnostic potential of mycobacterial antigens in serodiagnosis of
TB, 256 patients were enrolled in a study and divided into two groups: 126 smear
positive pulmonary TB patients (SPPT) and 130 smear-negative pulmonary TB
patients (SNPT); 152 bacillus Calmette-Guerin (BCG)-vaccinated healthy people
were used as a control. Murine results showed that antigens Rv0310c-E from RD 8
and Rv1255c-E from RD 10 were strongly immunogenic to Th1 cells and induced a
great humoral response. Receiver operating characteristic analysis indicated that
Rv0310c-E (area under the curve (AUC): 0.800) and Rv1255c-E (AUC: 0.808)
performed better than ESAT-6 (AUC: 0.665) and CFP-10 (AUC: 0.623) proteins but
were comparable with Rv3425 (AUC: 0.788) protein in a human serum IgG analysis.
Rv0310c-E demonstrated the highest diagnostic ability for the SPPT group (Youden
index: 0.5602, sensitivity: 69.84%, specificity: 86.18%), while Rv1255c-E
demonstrated the highest diagnostic ability for the SNPT group (Youden index:
0.5674, sensitivity: 73.84%, specificity: 82.89%). In addition, combination
analysis found that antigen Rv0310c-E, coupled with the Rv3425 protein (Youden
index: 0.6098, sensitivity: 87.30%, specificity: 73.68%) had the strongest
performance for TB diagnostics of the SPPT group, and the single antigen Rv1255c
E was strongest for the SNPT group. These results suggest that antigens Rv0310c-E
and Rv1255c-E are potential antigens for TB serodiagnostic tests, which may
facilitate detection of MTB in smear-negative and smear-positive patients.
PMID- 28698666
TI - Modelling person-to-person transmission in an Enterovirus A71 orally infected
hamster model of hand-foot-and-mouth disease and encephalomyelitis.
AB - Enterovirus A71 (EV-A71) causes hand-foot-and-mouth disease (HFMD), which may be
complicated by fatal encephalomyelitis. Although fecal-oral or oral-oral routes
are important in person-to-person transmission, how viral shedding and exposure
may predispose individuals to infection remains unknown. We investigated person
to-person transmission by using a model of HFMD and encephalomyelitis based on EV
A71 oral infection of 2-week-old hamsters. Animals (index animals) infected with
104 50% cell culture infective doses of virus uniformly developed severe disease
four days post-infection (dpi), whereas littermate contacts developed severe
disease after six to seven days of exposure to index animals. Virus was detected
in oral washes and feces at 3-4 dpi in index animals and at three to eight days
after exposure to index animals in littermate contact animals. In a second
experiment, non-littermate contact animals exposed for 8 or 12 h to index animals
developed the disease six and four days post-exposure, respectively. Tissues from
killed index and contact animals, studied by light microscopy,
immunohistochemistry and in situ hybridization, exhibited mild inflammatory
lesions and/or viral antigens/RNA in the squamous epithelia of the oral cavity,
tongue, paws, skin, esophagus, gastric epithelium, salivary glands, lacrimal
glands, central nervous system neurons, muscles (skeletal, cardiac and smooth
muscles) and liver. Orally shed viruses were probably derived from infected oral
mucosa and salivary glands, whereas fecal viruses may have derived from these
sites as well as from esophageal and gastric epithelia. Asymptomatic
seroconversion in exposed mother hamsters was demonstrated. Our hamster model
should be useful in studying person-to-person EV-A71 transmission and how drugs
and vaccines may interrupt transmission.
PMID- 28698667
TI - Phylogenetic analysis reveals two genotypes of the emerging fungus Mucor indicus,
an opportunistic human pathogen in immunocompromised patients.
AB - Mucormycosis is a rare fungal infection caused by Mucor indicus. Phylogenetic
analysis of many M. indicus isolates, mainly sampled from different clinical and
environmental specimens collected worldwide, revealed two genotypes, I and II,
based on ITS and D1/D2 LSU rDNA sequences. A retrospective review of the
literature revealed 13 cases. Eight (76.9%) patients had disseminated infections,
and the overall mortality rate was 30.7%. A pulmonary infection caused by M.
indicus genotype I in a liver transplant recipient was disseminated to include
the skin and was successfully treated with liposomal amphotericin B and
aggressive surgery. M. indicus can infect a wide variety of patients with no real
preference for the site of infection. We concluded that M. indicus has emerged as
a significant cause of invasive mycosis in severely immunocompromised patients
worldwide. Early diagnosis and initiation of appropriate therapy could enhance
survival in these immunocompromised patient populations.
PMID- 28698668
TI - Salmonella enterica serovar Typhimurium ST34 co-expressing blaNDM-5 and blaCTX-M
55 isolated in China.
PMID- 28698669
TI - Metabolomic similarities between bronchoalveolar lavage fluid and plasma in
humans and mice.
AB - This observational study catalogues the overlap in metabolites between matched
bronchoalveolar lavage fluid (BALF) and plasma, identifies the degree of
congruence between these metabolomes in human and mouse, and determines how
molecules may change in response to cigarette smoke (CS) exposure. Matched BALF
and plasma was collected from mice (ambient air or CS-exposed) and humans
(current or former smokers), and analyzed using mass spectrometry. There were
1155 compounds in common in all 4 sample types; fatty acyls and
glycerophospholipids strongly overlapped between groups. In humans and mice, more
than half of the metabolites present in BALF were also present in plasma. Mouse
BALF and human BALF had a strong positive correlation with 2040 metabolites in
common, suggesting that mouse models can be used to interrogate human lung
metabolome changes. While power was affected by small sample size in the mouse
study, the BALF metabolome appeared to be more affected by CS than plasma. CS
exposed mice showed increased plasma and BALF glycerolipids and
glycerophospholipids. This is the first report cataloguing the metabolites
present across mouse and human, BALF and plasma. Findings are relevant to
translational studies where mouse models are used to examine human disease, and
where plasma may be interrogated in lieu of BALF or lung tissue.
PMID- 28698670
TI - Urinary Extracellular Domain of Neurotrophin Receptor p75 as a Biomarker for
Amyotrophic Lateral Sclerosis in a Chinese cohort.
AB - To comprehensively assess whether p75ECD in urine could be a candidate biomarker
for ALS evaluation. Urine samples were collected from 101 ALS patients, 108
patients with other neurological disease (OND) and 97 healthy controls. 61 ALS
patients were followed up with clinical data including ALSFRS-r every 6 to 12
months, 23 ALS patients died and 17 ALS patients lost touch during follow up
period. Enzyme-linked immunoassay was employed to determine urine p75ECD
concentration. The ALSFRS-r was employed to assess the severity of ALS. The
concentration of p75ECD in ALS was significantly higher than that of OND and CTRL
(p < 0.001). Additionally, urine p75ECD concentrations in ALS-definite grade
patients were significantly higher than that in ALS-probable grade and ALS
possible grade patients (p < 0.001). Higher urine p75ECD concentrations were
correlated with increased clinical stage (p = 0.0309); urine p75ECD
concentrations and ALSFRS-r were negatively correlated (p = 0.022); and urine
p75ECD concentration in the fast-progressing ALS group was significantly higher
than that in slow-progression (p = 0.0026). Our finding indicates that urine
p75ECD concentration provides additional evidence for patients with clinically
suspected ALS, and can be employed to evaluate ALS-severity.
PMID- 28698671
TI - Morphology, composition, and mixing state of primary particles from combustion
sources - crop residue, wood, and solid waste.
AB - Morphology, composition, and mixing state of individual particles emitted from
crop residue, wood, and solid waste combustion in a residential stove were
analyzed using transmission electron microscopy (TEM). Our study showed that
particles from crop residue and apple wood combustion were mainly organic matter
(OM) in smoldering phase, whereas soot-OM internally mixed with K in flaming
phase. Wild grass combustion in flaming phase released some Cl-rich-OM/soot
particles and cardboard combustion released OM and S-rich particles.
Interestingly, particles from hardwood (pear wood and bamboo) and softwood
(cypress and pine wood) combustion were mainly soot and OM in the flaming phase,
respectively. The combustion of foam boxes, rubber tires, and plastic
bottles/bags in the flaming phase released large amounts of soot internally mixed
with a small amount of OM, whereas the combustion of printed circuit boards and
copper-core cables emitted large amounts of OM with Br-rich inclusions. In
addition, the printed circuit board combustion released toxic metals containing
Pb, Zn, Sn, and Sb. The results are important to document properties of primary
particles from combustion sources, which can be used to trace the sources of
ambient particles and to know their potential impacts in human health and
radiative forcing in the air.
PMID- 28698672
TI - Metabolic Effects of Clenbuterol and Salbutamol on Pork Meat Studied Using
Internal Extractive Electrospray Ionization Mass Spectrometry.
AB - Direct mass spectrometry analysis of metabolic effects of clenbuterol and
salbutamol on pork quality at the molecular level is incredibly beneficial for
food regulations, public health and the development of new anti-obesity drugs.
With internal extractive electrospray ionization mass spectrometry (iEESI-MS),
nutrients including creatine, amino acids, L-carnitine, vitamin B6, carnosine and
phosphatidylcholines in pork tissue were identified, without sample pretreatment,
using collision-induced dissociation (CID) experiments and by comparison with
authentic compounds. Furthermore, normal pork samples were clearly differentiated
from pork samples with clenbuterol and salbutamol via principal component
analysis (PCA). Correlation analysis performed on the spectral data revealed that
the above-mentioned nutrients strongly correlated with pork quality, and the
absolute intensity of phosphatidylcholines in normal pork was much higher than
pork contaminated by clenbuterol and salbutamol. Our findings suggested that
clenbuterol and salbutamol may render effects on the activity of carnitine
acyltransferase I, hence the process that L-carnitine transports long-chain fatty
acids into mitochondria and the formation of phosphatidylcholines might be
affected. However, the underlying metabolic mechanisms of clenbuterol and
salbutamol on carnitine acyltransferase I requires more comprehensive studies in
future work.
PMID- 28698673
TI - A quinolinol-based small molecule with anti-MRSA activity that targets bacterial
membrane and promotes fermentative metabolism.
AB - In a loss-of-viability screen of small molecules against methicillin-resistant
Staphylococcus aureus (MRSA) USA300, we found a small molecule, designated DNAC
2, which has an MIC of 8 MUg ml-1. DNAC-2 is a quinolinol derivative that is
bactericidal at 2X MIC. Macromolecular synthesis assays at 2 * MIC of DNAC-2
revealed inhibition of DNA, cell wall, RNA and protein synthesis within fifteen
to thirty minutes of treatment when compared to the untreated control.
Transmission electron microscopy of DNAC-2-treated cells revealed a significantly
thicker cell wall and impaired daughter cell separation. Exposure of USA300 cells
to 1 * MIC of DNAC-2 resulted in mislocalization of PBP2 away from the septum in
an FtsZ-independent manner. In addition, membrane localization with FM4-64, as
well as depolarization study with DiOC2 and lipophilic cation TPP+ displayed
membrane irregularities and rapid membrane depolarization, respectively, in DNAC
2-treated cells vs -untreated control. However, DNAC-2 exhibited almost no
toxicity toward eukaryotic membranes. Notably, DNAC-2 drives energy generation
toward substrate level phosphorylation and the bacteria become more sensitive to
DNAC-2 under anaerobic conditions. We propose that DNAC-2 affects USA300 by
targeting the membrane, leading to partial membrane depolarization and
subsequently affecting aerobic respiration and energy-dependent functional
organization of macromolecular biosynthetic pathways. The multiple effects may
have the desirable consequence of limiting the emergence of resistance to DNAC-2.
PMID- 28698674
TI - Insight into synergetic mechanisms of tetracycline and the selective serotonin
reuptake inhibitor, sertraline, in a tetracycline-resistant strain of Escherichia
coli.
AB - Sertraline, an antidepressive drug, has been reported to inhibit general
bacterial efflux pumps. In the present study, we report for the first time a
synergistic effect of sertraline and tetracycline in a TetA-encoded tetracycline
resistant strain of Escherichia coli. Synergy between sertraline and tetracycline
in an E. coli strain with TetA-mediated tetracycline resistance (E. coli APEC_O2)
was assessed by the MIC and checkerboard assays. The global transcriptome of E.
coli APEC_O2 exposed to 1/2 MIC concentrations of sertraline and/or tetracycline
was analyzed to elucidate the interaction mechanism between sertraline and
tetracycline. The fractional inhibitory concentration index for tetracycline and
sertraline in E. coli APEC_O2 was 0.5. In addition, in the presence of 1/2 MIC of
sertraline, the sensitivity of E. coli APEC_O2 to tetracycline could be restored
according to clinical standards (from 64 to 4 mg l-1). RNA data suggest changes
in respiration that is likely to decrease intracellular pH and thereby the proton
motive force, which provides the energy for the tetracycline efflux pump.
Furthermore, sertraline and tetracycline may induce a change from oxidation to
fermentation in the E.coli, which further decreases pH, resulting in cell death.
This study shows that sertraline interacts with tetracycline in a synergistic and
AcrAB-TolC pump-independent manner. The combinational treatment was further shown
to induce many changes in the global transcriptome, including altered tetA and
tetR expression. The results indicate that sertraline may be used as a helper
compound with the aim to reverse tetracycline resistance encoded by tetA.
PMID- 28698675
TI - Virgisporangium myanmarense sp. nov., a novel motile actinomycete isolated from
an anthill soil in Myanmar.
AB - An actinomycete strain, designated MM04-1133T, was isolated from an anthill soil
sample collected in Bagan, Myanmar. To establish the taxonomic status of this
strain, the isolate was subjected to a polyphasic approach. Strain MM04-1133T was
Gram-staining positive, aerobic, motile and formed long and narrow sporangia
directly above the surface of the substrate mycelium. Whole-cell hydrolysates of
the strain contained 3-OH-diaminopimelic acid, arabinose, glucose, galactose,
mannose, rhamnose and xylose. The predominant menaquinones were MK-10(H6) and MK
10(H8). The major cellular fatty acids were iso-C16:0 and anteiso-C17:0. The
diagnostic phospholipid was phosphatidylethanolamine. The G+C content of the DNA
was 69.1 mol%. Phylogenetic analysis based on 16S rRNA gene sequence revealed
that strain MM04-1133T clustered within the genus Virgisporangium, with the
sequence exhibiting highest similarity (98.5% identity) with Virgisporangium
ochraceum NBRC 16418T. The strain grew in the presence of 0-1% (w/v) NaCl, at pH
5-8 and at 20-40 degrees C, with optimal growth at 30-37 degrees C. Based on
phylogenetic analysis and chemotaxonomic and phenotypic data, we propose
classifying this isolate as a novel species of the genus Virgisporangium, to be
designated as Virgisporangium myanmarense sp. nov. The type strain is MM04-1133T
(=NBRC 112733T=VTCC 910008T).
PMID- 28698676
TI - New anti-inflammatory metabolites produced by Streptomyces violaceoruber isolated
from Equus burchelli feces.
AB - Three new metabolites (2-4), together with one known compound, GTRI-02, (1) were
isolated from a fermentation broth of Streptomyces violaceoruber derived from
Equus burchelli feces. The structures of the new compounds 2-4 were established
using comprehensive NMR spectroscopic data analysis as well as UV, IR and MS
data. The anti-inflammatory activity of compounds 1-4 was tested by examining
their ability to inhibit nitric oxide (NO) production in lipopolysaccharide (LPS)
stimulated RAW 264.7 macrophage cells. Compound 2 showed a moderate inhibition of
NO production with IC50 value of 51.2 MUm.
PMID- 28698677
TI - Precise spatio-temporal control of rapid optogenetic cell ablation with mem
KillerRed in Zebrafish.
AB - The ability to kill individual or groups of cells in vivo is important for
studying cellular processes and their physiological function. Cell-specific
genetically encoded photosensitizing proteins, such as KillerRed, permit
spatiotemporal optogenetic ablation with low-power laser light. We report
dramatically improved resolution and speed of cell targeting in the zebrafish
kidney through the use of a selective plane illumination microscope (SPIM).
Furthermore, through the novel incorporation of a Bessel beam into the SPIM
imaging arm, we were able to improve on targeting speed and precision. The low
diffraction of the Bessel beam coupled with the ability to tightly focus it
through a high NA lens allowed precise, rapid targeting of subsets of cells at
anatomical depth in live, developing zebrafish kidneys. We demonstrate that these
specific targeting strategies significantly increase the speed of optoablation as
well as fish survival.
PMID- 28698678
TI - Prototype of a bistable polariton field-effect transistor switch.
AB - Microcavity exciton polaritons are promising candidates to build a new generation
of highly nonlinear and integrated optoelectronic devices. Such devices range
from novel coherent light emitters to reconfigurable potential landscapes for
electro-optical polariton-lattice based quantum simulators as well as building
blocks of optical logic architectures. Especially for the latter, the strongly
interacting nature of the light-matter hybrid particles has been used to
facilitate fast and efficient switching of light by light, something which is
very hard to achieve with weakly interacting photons. We demonstrate here that
polariton transistor switches can be fully integrated in electro-optical schemes
by implementing a one-dimensional polariton channel which is operated by an
electrical gate rather than by a control laser beam. The operation of the device,
which is the polariton equivalent to a field-effect transistor, relies on
combining electro-optical potential landscape engineering with local exciton
ionization to control the scattering dynamics underneath the gate. We furthermore
demonstrate that our device has a region of negative differential resistance and
features a completely new way to create bistable behavior.
PMID- 28698679
TI - Raman scattering excitation spectroscopy of monolayer WS2.
AB - Resonant Raman scattering is investigated in monolayer WS2 at low temperature
with the aid of an unconventional technique, i.e., Raman scattering excitation
(RSE) spectroscopy. The RSE spectrum is made up by sweeping the excitation
energy, when the detection energy is fixed in resonance with excitonic
transitions related to either neutral or charged excitons. We demonstrate that
the shape of the RSE spectrum strongly depends on the selected detection energy.
The resonance of outgoing light with the neutral exciton leads to an extremely
rich RSE spectrum, which displays several Raman scattering features not reported
so far, while no clear effect on the associated background photoluminescence is
observed. Instead, when the outgoing photons resonate with the negatively charged
exciton, a strong enhancement of the related emission occurs. Presented results
show that the RSE spectroscopy can be a useful technique to study electron-phonon
interactions in thin layers of transition metal dichalcogenides.
PMID- 28698681
TI - A Revision of the Veterinarian's Oath.
PMID- 28698680
TI - Activated Monocytes Enhance Platelet-Driven Contraction of Blood Clots via Tissue
Factor Expression.
AB - Platelet-driven reduction in blood clot volume (clot contraction or retraction)
has been implicated to play a role in hemostasis and thrombosis. Although these
processes are often linked with inflammation, the role of inflammatory cells in
contraction of blood clots and thrombi has not been investigated. The aim of this
work was to study the influence of activated monocytes on clot contraction. The
effects of monocytes were evaluated using a quantitative optical tracking
methodology to follow volume changes in a blood clot formed in vitro. When a
physiologically relevant number of isolated human monocytes pre-activated with
phorbol-12-myristate-13-acetate (PMA) were added back into whole blood, the
extent and rate of clot contraction were increased compared to addition of non
activated cells. Inhibition of tissue factor expression or its inactivation on
the surface of PMA-treated monocytes reduced the extent and rate of clot
contraction back to control levels with non-activated monocytes. On the contrary,
addition of tissue factor enhanced clot contraction, mimicking the effects of
tissue factor expressed on the activated monocytes. These data suggest that the
inflammatory cells through their expression of tissue factor can directly affect
hemostasis and thrombosis by modulating the size and density of intra- and
extravascular clots and thrombi.
PMID- 28698682
TI - Advocacy is key.
PMID- 28698684
TI - 2016 Annual Report of the Canadian Veterinary Medical Association.
PMID- 28698683
TI - Ethical question of the month - July 2017.
PMID- 28698685
TI - Management of a tracheal intussusception in a dog.
AB - A 5-year-old Belgian Malinois dog was presented for evaluation of dyspnea of 1
month duration. Tracheal intussusception was diagnosed by tracheoscopy. Treatment
consisted of surgical resection of the invaginated tracheal ring and the
immediate cranial and caudal tracheal rings. The dog recovered uneventfully;
complications included temporary emphysema after surgery. Seven months after
surgery, the dog was still clinically normal. To the authors' knowledge, this is
the first report of a tracheal intussusception treated surgically in a dog.
PMID- 28698686
TI - Fluoroscopic and endoscopic diagnosis of a lower esophageal ring causing foreign
body impaction in a dog.
AB - A dog was presented because of regurgitation over a 3-day period. Radiographic
examination revealed a bean-shaped filling defect and an annular narrowing at the
level of the gastroesophageal sphincter. The contractile ring-like structure was
sharply demarcated, and its appearance varied according to gastroesophageal
distension. Endoscopic findings revealed lower esophageal ring and foreign body
impaction.
PMID- 28698687
TI - Hemoabdomen secondary to high grade lymphoma.
AB - A 10-year-old castrated male Labrador retriever dog was presented for evaluation
of a right elbow mass. Mandibular lymphadenopathy was noted on physical
examination. Following sudden death after discharge, a necropsy was performed.
Cause of death was determined to be due to hemoabdomen secondary to high grade
lymphoma.
PMID- 28698688
TI - Retro-orbital and disseminated B-cell lymphoma in a yellow-collared macaw
(Primolius auricollis).
AB - A yellow-collared macaw was presented with unilateral left exophthalmia. The
complete blood cell count and biochemistry revealed a heterophilic leukocytosis
and elevation in liver parameters, respectively. A computed tomography scan
showed a contrast-enhancing retrobulbar mass and hepatomegaly. Cytology of the
liver was consistent with a round cell tumor, most likely lymphoma. The bird died
after 2 months of palliative care. Postmortem examination confirmed a retro
orbital and disseminated B-cell lymphoma.
PMID- 28698689
TI - Syndrome of inappropriate antidiuretic hormone secretion in a dog with a
histiocytic sarcoma.
AB - A 7-year-old female neutered Bernese mountain dog was presented in a semi
comatose state. Based on serum hypo-osmolality with inappropriate urine hyper
osmolality and urine sodium excretion, the dog was diagnosed with a syndrome of
inappropriate antidiuretic hormone secretion secondary to a histiocytic sarcoma.
This report describes the first case of this syndrome in a dog with histiocytic
sarcoma.
PMID- 28698690
TI - Equine recurrent uveitis in western Canadian prairie provinces: A retrospective
study (2002-2015).
AB - The objectives of this study were to determine the demographics of horses with
equine recurrent uveitis (ERU) presenting to the Western College of Veterinary
Medicine and to describe and compare the prognosis of ERU in the Appaloosa with
that in other breeds. Horses diagnosed with ERU by a veterinary ophthalmologist
between 2002 and 2015 were included. Eye lesions were classified as mild,
moderate, or severe based on clinical manifestations. Breed, age, severity,
blindness, and final outcome were evaluated. Thirty-two horses fit the inclusion
criteria; 62.5% were Appaloosas. Mean age at presentation was 12.13 +/- 4.6
years. Equine recurrent uveitis was bilateral in 93.6% of horses and was severe
in 59.4% of eyes at presentation. Bilateral blindness was present in 59.4% of
horses at last follow-up. Of 27 horses available for follow-up, 63% were
euthanized due to ERU. No significant differences in age, severity, blindness, or
rate of euthanasia were noted between Appaloosas and other breeds. The Appaloosa
is at increased risk for ERU, which is a devastating ocular disease.
PMID- 28698691
TI - Expected consequences of convenience euthanasia perceived by veterinarians in
Quebec.
AB - In companion animal practice, convenience euthanasia (euthanasia of a physically
and psychologically healthy animal) is recognized as one of the most difficult
situations. There is little published on veterinary perceptions of the
consequences of convenience euthanasia. A qualitative study on the subject based
on interviews with 14 veterinarians was undertaken. The animal's interests in the
dilemma of convenience euthanasia was taken into consideration, strictly from the
point of view of the physical suffering and stress related to the procedure. The
veterinarian's goal was to respect the animal's interests by controlling physical
pain. Most often, veterinarians made their own interests and those of the owners
a priority when considering the consequences of their decision to perform or
refuse convenience euthanasia.
PMID- 28698692
TI - Cardiovascular effects of constant rate infusions of lidocaine, lidocaine and
dexmedetomidine, and dexmedetomidine in dogs anesthetized at equipotent doses of
sevoflurane.
AB - This study evaluated the cardiovascular effects of a constant rate infusion (CRI)
of lidocaine, lidocaine and dexmedetomidine, and dexmedetomidine in dogs
anesthetized with sevoflurane at equipotent doses. Treatments consisted of T1
Lidocaine [loading dose 2 mg/kg body weight (BW), IV, and CRI of 100 MUg/kg BW
per min] at 1.4% end-tidal of sevoflurane (FESEV); T2-Dexmedetomidine (loading
dose 2 MUg/kg BW, IV, and CRI of 2 MUg/kg BW per hour) and FESEV 1.1%; and T3
Lidocaine-Dexmedetomidine using the same doses of T1 and T2 and FESEV 0.8%.
Constant rate infusion of lidocaine did not induce any cardiovascular changes;
lidocaine and dexmedetomidine resulted in cardiovascular effects similar to
dexmedetomidine alone. These effects were characterized by a significant (P <
0.001) decrease in heart rate, cardiac output, cardiac index, oxygen delivery,
and pulmonary vascular resistance index, and a significant (P < 0.001) increase
in mean and diastolic arterial pressure, systemic vascular resistance index,
pulmonary arterial occlusion pressure and oxygen extraction ratio, compared with
baseline values. In conclusion, a CRI of lidocaine combined with dexmedetomidine
produces significant cardiovascular changes similar to those observed with
dexmedetomidine alone.
PMID- 28698693
TI - Comparison of an online learning module to hands-on training in teaching a
cautery disbudding technique for dairy calves including cornual nerve block
application.
AB - Disbudding and dehorning are common procedures on dairy farms. In a recent survey
of Ontario dairy producers, 38% reported not using local anesthetic for these
procedures. Use of pain control is important for both calf welfare and industry
sustainability. Use of local anesthetic requires technical training, typically
provided by a veterinarian, although online training videos also exist. Neither
method has been studied for efficacy. Our objective was to compare an online
module to hands-on training in teaching naive participants (veterinary students)
to effectively carry out a cornual nerve block and disbud a dairy calf.
Participants were assigned to either an online or hands-on training group.
Although no statistical differences were seen in success of the nerve block,
online learners were less confident and had poorer technical skills. While online
learning was surprisingly effective for a psycho-motor skill, best practices
should include hands-on training.
PMID- 28698694
TI - Efficiency of medetomidine for epidural analgesia: Effects on isoflurane
requirement and mean systemic arterial blood pressure in dogs.
AB - Five healthy beagle dogs anesthetized with isoflurane were administered
medetomidine (alpha-2 adrenoceptor agonist) by the epidural route. Mean arterial
pressure (MAP) and end-tidal concentration of isoflurane (ISO) were measured 1,
2.5, and 4 h after administration. Epidural administration of medetomidine
reduced the isoflurane dose required to prevent changes in vital parameters
following mechanical stimulation and maintained the MAP at a higher level
compared to the control.
PMID- 28698695
TI - Canine oral papillomavirus outbreak at a dog daycare facility.
AB - This report describes an outbreak at a dog daycare facility where 13 of 52 dogs
developed suspected canine papillomavirus (CPV) infection. Based on contact
tracing, subclinical CPV shedding was speculated. Active surveillance, exclusion
of animals with active or recent infection and cohort formation may have been
effective in stopping the outbreak.
PMID- 28698696
TI - Is melatonin of value in cancer treatment? Experience with a case of feline
mammary carcinoma.
PMID- 28698697
TI - Non-DVM wages and trends across Canada.
PMID- 28698698
TI - Diagnostic Ophthalmology.
PMID- 28698699
TI - No benefit to women or fetuses.
PMID- 28698700
TI - Terms of endearment: Reason and science speak for embryonic humans and fetal
humans.
PMID- 28698701
TI - Face transplants.
PMID- 28698702
TI - Six questions about physician-assisted death from a conscientious objector.
PMID- 28698703
TI - Why are suicide rates climbing after years of decline?
AB - There is evidence that the increasing rates of suicide can be linked to the
legalization of physician-assisted suicide. Factors such as suicide contagion and
the increasing positive media reporting on such suicides are also relevant and
have led to different standards of treatment for suicidal people who claim the
right to have their suicides medically assisted.
PMID- 28698704
TI - Baptism in the ICU.
PMID- 28698705
TI - Effects of short-term medical mission trips to Chiapas, Mexico, on the
religiosity of the missionaries.
AB - : This study evaluates the effects that short-term, foreign, Catholic medical
mission trips had on the religiosity of the United States-based participants. The
subjects of this study participated in Catholic medical missions to Chiapas
State, Mexico, in 2014 and 2015. Twenty-two of forty-two participants responded
to a survey to assess for any changes in their religiosity and associated
attitudes and behaviors. The results revealed that participation in the medical
mission was associated with a significant increase in non-organizational
religious activity, intrinsic religiosity, concern for health disparities and the
burden of illness in the developing world, the promotion of further missions, the
provision of service and/or monetary aid to the poor in the missionary's local
community, and an increased likelihood to discuss the Christian faith in
conversations with others. There was no statistically significant association
with organizational religious activity or local participation in evangelization
activities. SUMMARY: This article reports on the changes seen in the religious
attitudes and charitable works performed following participation in a short-term
medical mission. After serving on a mission trip to Mexico, we found that United
States-based missionaries had an increase in their private religious activities,
felt closer to God, were more likely to help the poor in their own neighborhoods,
and were more likely to discuss their Christian faith than prior to the mission
trip. We discuss possible reasons for these changes.
PMID- 28698706
TI - Personhood status of the human zygote, embryo, fetus.
AB - The fields of biology, medicine, and embryology have described the developmental
milestones of humans throughout gestation in great detail. It is less clear as to
when humans are recognized as people, persons, or beings with rights that are
protected by legislation. The practice of law is irrevocably intertwined with
that of ethical conduct; and the time at which a human life is considered a
person has implications that extend to health care, legislation on abortion, and
autonomy of individuals. This article reviews the economical position that
fertilization is the moment that personhood of the conceptus begins. Alternate
positions proposing that personhood begins at other possible times after
fertilization are presented and contrasted to the economical hypothesis. Summary:
This article is an original work critically analyzing the various arguments for
human personhood at fertilization and thereafter. The various positions on human
personhood are compared and contrasted herein. The time of the human lifespan at
which personhood is conferred has important implications for health care,
legislation, and personal autonomy.
PMID- 28698707
TI - Identifying organisms.
AB - : Defenders of human, embryonic, destructive stem-cell research and early
abortion typically argue for their position by showing that you and I do not come
into existence at conception but rather at some point after. Eugene Mills has
provided an ingenious argument that you and I could not have come into existence
at conception. I argue against Mills's argument on two counts: first, his
argument depends upon a cursory limning of human conception, and when fuller
details are considered, a premise in his argument is undercut. Second, Mills's
argument invites us to ask questions about how to identify individual organisms.
Given a fuller description of human conception and some plausible metaphysical
principles, I argue that Mills should hold instead that you and I do in fact come
into being at conception. SUMMARY: One way to argue that early abortions are
permissible is to argue against the view that you and I come into existence at
conception. Most abortion rights defenders argue for this conclusion by noting
that in order for you and I to exist, there must be developed psychological
capacities. Eugene Mills takes a different route and argues that you and I could
not come into existence at conception because that would mean being identical to
an egg - which he rightly notes we cannot be. I argue against Mills in this
article.
PMID- 28698708
TI - Pope John Paul II and the neurological standard for the determination of death: A
critical analysis of his address to the Transplantation Society.
AB - : The introduction of the "brain death" criterion constitutes a significant
paradigm shift in the determination of death. The perception of the public at
large is that the Catholic Church has formally endorsed this neurological
standard. However, a critical reading of the only magisterial document on this
subject, Pope John Paul II's 2000 address, shows that the pope's acceptance of
the neurological criterion is conditional in that it entails a twofold
requirement. It requires that certain medical presuppositions of the neurological
standard are fulfilled, and that its philosophical premise coheres with the
Church's teaching on the body-soul union. This article demonstrates that the
medical presuppositions are not fulfilled, and that the doctrine of the brain as
the central somatic integrator of the body does not cohere either with the
current holistic understanding of the human organism or with the Church's
Thomistic doctrine of the soul as the form of the body. SUMMARY: The concept of
"brain death" (the neurological basis for legally declaring a person dead) has
caused much controversy since its inception. In this regard, it has been
generally perceived that the Catholic Church has officially affirmed the "brain
death" criterion. The address of Pope John Paul II in 2000 shows, however, that
he only gave it a conditional acceptance, one which requires that several medical
and philosophical presuppositions of the "brain death" standard be fulfilled.
This article demonstrates, taking into consideration both the empirical evidence
and the Church's Thomistic anthropology, that the presuppositions have not been
fulfilled.
PMID- 28698710
TI - Editorial.
PMID- 28698709
TI - A Developmental Lexical Bias in the Interpretation of Discrepant Messages.
AB - Children's interpretations of lexical and vocal cues to speaker affect,
independently and in combination, were examined in four studies. In Experiments 1
and 2, 7- to 11 -year-olds'judgments of lexical and paralinguistic cues were
evaluated. In Experiment 3, these cues were combined to produce consistent and
discrepant messages. The affective interpretations of 7- to 10-year-olds
reflected a weighted-averaging strategy favoring the affect conveyed lexically.
In Experiment 4, the developmental trajectory of children's interpretations of
discrepancy from 4 to 10 years of age was investigated. Both 4- and 7-year-olds
appeared to use a weighted-averaging strategy favoring lexical content, whereas
10-year-olds utilized a strategy favoring paralanguage.
PMID- 28698712
TI - The Neural Basis for Sleep Regulation - Data Assimilation from Animal to Model.
AB - Sleep is important for normal brain function, and sleep disruption is comorbid
with many neurological diseases. There is a growing mechanistic understanding of
the neurological basis for sleep regulation that is beginning to lead to
mechanistic mathematically described models. It is our objective to validate the
predictive capacity of such models using data assimilation (DA) methods. If such
methods are successful, and the models accurately describe enough of the
mechanistic functions of the physical system, then they can be used as
sophisticated observation systems to reveal both system changes and sources of
dysfunction with neurological diseases and identify routes to intervene. Here we
report on extensions to our initial efforts [1] at applying unscented Kalman
Filter (UKF) to models of sleep regulation on three fronts: tools for multi
parameter fitting; a sophisticated observation model to apply the UKF for
observations of behavioral state; and comparison with data recorded from
brainstem cell groups thought to regulate sleep.
PMID- 28698711
TI - Anti-N-Methyl-D-aspartate Receptor Encephalitis: A Severe, Potentially Reversible
Autoimmune Encephalitis.
AB - Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is potentially lethal,
but it is also a treatable autoimmune disorder characterized by prominent
psychiatric and neurologic symptoms. It is often accompanied with teratoma or
other neoplasm, especially in female patients. Anti-NMDAR antibodies in
cerebrospinal fluid (CSF) and serum are characteristic features of the disease,
thereby suggesting a pathogenic role in the disease. Here, we summarize recent
studies that have clearly documented that both clinical manifestations and the
antibodies may contribute to early diagnosis and multidisciplinary care. The
clinical course of the disorder is reversible and the relapse could occur in some
patients. Anti-NMDAR encephalitis coexisting with demyelinating disorders makes
the diagnosis more complex; thus, clinicians should be aware of the overlapping
diseases.
PMID- 28698713
TI - Self-Grouping Multi-Network Clustering.
AB - Joint clustering of multiple networks has been shown to be more accurate than
performing clustering on individual networks separately. Many multi-view and
multi-domain network clustering methods have been developed for joint multi
network clustering. These methods typically assume there is a common clustering
structure shared by all networks, and different networks can provide
complementary information on this underlying clustering structure. However, this
assumption is too strict to hold in many emerging real-life applications, where
multiple networks have diverse data distributions. More popularly, the networks
in consideration belong to different underlying groups. Only networks in the same
underlying group share similar clustering structures. Better clustering
performance can be achieved by considering such groups differently. As a result,
an ideal method should be able to automatically detect network groups so that
networks in the same group share a common clustering structure. To address this
problem, we propose a novel method, ComClus, to simultaneously group and cluster
multiple networks. ComClus treats node clusters as features of networks and uses
them to differentiate different network groups. Network grouping and clustering
are coupled and mutually enhanced during the learning process. Extensive
experimental evaluation on a variety of synthetic and real datasets demonstrates
the effectiveness of our method.
PMID- 28698714
TI - Corrigendum: Adenosine Kinase Inhibition Protects against Cranial Radiation
Induced Cognitive Dysfunction.
AB - [This corrects the article on p. 42 in vol. 9, PMID: 27375429.].
PMID- 28698715
TI - Erratum: Torpor: The Rise and Fall of 3-Monoiodothyronamine from Brain to Gut
From Gut to Brain?
AB - [This corrects the article on p. 118 in vol. 8, PMID: 28620354.].
PMID- 28698716
TI - Corrigendum: The Arabidopsis ANGUSTIFOLIA3-YODA Gene Cascade Induces Anthocyanin
Accumulation by Regulating Sucrose Levels.
AB - [This corrects the article on p. 1728 in vol. 7, PMID: 27920784.].
PMID- 28698717
TI - From Blood to Lesioned Brain: An In Vitro Study on Migration Mechanisms of Human
Nasal Olfactory Stem Cells.
AB - Stem cell-based therapies critically rely on selective cell migration toward
pathological or injured areas. We previously demonstrated that human olfactory
ectomesenchymal stem cells (OE-MSCs), derived from an adult olfactory lamina
propria, migrate specifically toward an injured mouse hippocampus after
transplantation in the cerebrospinal fluid and promote functional recoveries.
However, the mechanisms controlling their recruitment and homing remain elusive.
Using an in vitro model of blood-brain barrier (BBB) and secretome analysis, we
observed that OE-MSCs produce numerous proteins allowing them to cross the
endothelial wall. Then, pan-genomic DNA microarrays identified signaling
molecules that lesioned mouse hippocampus overexpressed. Among the most
upregulated cytokines, both recombinant SPP1/osteopontin and CCL2/MCP-1 stimulate
OE-MSC migration whereas only CCL2 exerts a chemotactic effect. Additionally, OE
MSCs express SPP1 receptors but not the CCL2 cognate receptor, suggesting a CCR2
independent pathway through other CCR receptors. These results confirm that OE
MSCs can be attracted by chemotactic cytokines overexpressed in inflamed areas
and demonstrate that CCL2 is an important factor that could promote OE-MSC
engraftment, suggesting improvement for future clinical trials.
PMID- 28698719
TI - Long-Term Safety of Transplanting Human Bone Marrow Stromal Cells into the
Extravascular Spaces of the Choroid of Rabbits.
AB - Incurable neuroretinal degeneration diseases cause severe vision loss and
blindness in millions of patients worldwide. In previous studies, we demonstrated
that transplanting human bone marrow stromal cells (hBMSCs) in the extravascular
spaces of the choroid (EVSC) of the Royal College of Surgeon rats ameliorated
retinal degeneration for up to 5 months. Assessing the safety of hBMSC treatment
and graft survival in a large animal is a crucial step before initiating clinical
trials. Here, we transplanted hBMSCs into the EVSC compartment of New Zealand
White rabbits. No immunosuppressants were used. Transplanted cells were spread
across the EVSC covering over 80 percent of the subretinal surface. No cells were
detected in the sclera. Cells were retained in the EVSC compartment 10 weeks
following transplantation. Spectral domain optical coherence tomography (SD-OCT)
and histopathology analysis demonstrated no choroidal hemorrhages, retinal
detachment, inflammation, or any untoward pathological reactions in any of
transplanted eyes or in the control noninjected contralateral eyes. No reduction
in retinal function was recorded by electroretinogram up to 10 weeks following
transplantation. This study demonstrates the feasibility and safety of
transplanting hBMSCs in the EVSC compartment in a large eye model of rabbits.
PMID- 28698720
TI - Corrigendum to "Therapeutic Potential of Olfactory Ensheathing Cells and
Mesenchymal Stem Cells in Spinal Cord Injuries".
AB - [This corrects the article DOI: 10.1155/2017/3978595.].
PMID- 28698718
TI - The Holy Grail of Orthopedic Surgery: Mesenchymal Stem Cells-Their Current Uses
and Potential Applications.
AB - Only select tissues and organs are able to spontaneously regenerate after disease
or trauma, and this regenerative capacity diminishes over time. Human stem cell
research explores therapeutic regenerative approaches to treat various
conditions. Mesenchymal stem cells (MSCs) are derived from adult stem cells; they
are multipotent and exert anti-inflammatory and immunomodulatory effects. They
can differentiate into multiple cell types of the mesenchyme, for example,
endothelial cells, osteoblasts, chondrocytes, fibroblasts, tenocytes, vascular
smooth muscle cells, and sarcomere muscular cells. MSCs are easily obtained and
can be cultivated and expanded in vitro; thus, they represent a promising and
encouraging treatment approach in orthopedic surgery. Here, we review the
application of MSCs to various orthopedic conditions, namely, orthopedic trauma;
muscle injury; articular cartilage defects and osteoarthritis; meniscal injuries;
bone disease; nerve, tendon, and ligament injuries; spinal cord injuries;
intervertebral disc problems; pediatrics; and rotator cuff repair. The use of
MSCs in orthopedics may transition the practice in the field from predominately
surgical replacement and reconstruction to bioregeneration and prevention.
However, additional research is necessary to explore the safety and effectiveness
of MSC treatment in orthopedics, as well as applications in other medical
specialties.
PMID- 28698721
TI - Is Herpes Simplex virus (HSV) a sign of Encephalitis in Iranian Newborns?
Prevalence of HSV Infection in Pregnant Women in Iran: A Systematic Review and
Meta-Analysis.
AB - OBJECTIVE: Herpes Simplex virus (HSV) is one of the most common sexually
transmitted diseases in the world. This study aimed to determine the prevalence
of herpes simplex virus in pregnant women in Iran. MATERIALS & METHODS: A
systematic literature review was conducted to study the HSV subtypes in Persian
and English papers through several databases. We searched Pub Med, Scopus, Ovid,
Science Direct and national databases as Magiran, Iranmedex and Science
Information Database (SID) up to October 2015. Random-effects model were applied
to calculate the pooled prevalence of HSV subtypes. RESULTS: Five eligible
studies were identified, including 1140 participants. The pooled prevalence of
HSV infection in pregnant women was 0.64% (95% CI: 0.10- 1.18) in Iran. The
pooled prevalence of studies on both HSV-1 and HSV-2 was 0.91% (CI: 0.81-1.02)
and studies on only HSV-2 was 0.23% (CI: -0.61-0.63), respectively. CONCLUSION:
The prevalence of HSV infection in pregnant women in Iran was higher. HSV
infection of the central nervous system, especially with HSV-2, can also cause
recurrent aseptic meningitis and monophasic, as well as radiuculitis or myelitis.
The performance of screening to detect infection in pregnant women can play an
important role in the prevention and treatment of patients and help to prevent
the transmission of HSV infection to infants in Iran.
PMID- 28698722
TI - Infantile Spasms Treated with Intravenous Methypredinsolone Pulse.
AB - OBJECTIVE: Infantile spasms is diagnosed late even by expert pediatricians. Late
diagnosis (later than 3 weeks) can have a negative effect on the long-term
prognosis. We aimed to investigate infantile spasms treated with intravenous
methylprednisolone pulse. MATERIALS & METHODS: In this case series study, 20
infants with infantile spasms in 17-Shahrivar Hospital, Rasht, Iran were
enrolled. Drugs were administered based on Mytinger protocol that included 3 days
of methylprednisolone pulse and 56 days of oral prednisolone. The control of
spasms and the omission of hypsarrhythmia in infants follow-up were the primary
and secondary outcomes, respectively. Remission was indicated if the caregivers
mentioned no spasms or >50% decrease regarding drug initiation for at least 5
consecutive days and the electroencephalography during sleep period noted the
omission of hypsarrhythmia. RESULTS: Eleven female (55%) and 9 male (45%)
patients with the mean age of 4.95+/-1.39 months were enrolled. Mean rapid
remission was noted as 4.41+/-1.50 days. Twelve patients (60%) noted early
remission. seizure was controlled in 3(15%) patients completely after 24 months.
Five (25%) occasional seizures were noted controlled by routine anticonvulsant
drugs after 24 months and 12 (60%) no response was mentioned. Most of the
patients (65%) had cryptogenic etiology for infantile spasms. Uncontrolled
seizure was mentioned after initial remission. CONCLUSION: Methyl prednisolone is
an appropriate drug based on easy administering, low cost, and its accessibility.
PMID- 28698723
TI - Socioeconomic Status Index to Interpret Inequalities in Child Development.
AB - OBJECTIVE: There have been contradictory findings on the relationship between
Socioeconomic Status (SES) and child development although SES is associated with
child development outcomes. The present study intended to define the relationship
between SES and child development in Tehran kindergartens, Iran. MATERIALS &
METHODS: This cross-sectional survey studied 1036 children aged 36-60 month, in
different kindergartens in Tehran City, Iran, in 2014-2015. The principal factor
analysis (PFA) model was employed to construct SES indices. The constructed SES
variable was employed as an independent variable in logistic regression model to
evaluate its role in developmental delay as a dependent variable. RESULTS: The
relationship between SES and developmental delay was significant at P=0.003. SES
proved to have a significant (P<0.05) impact on developmental delay, both as an
independent variable and after controlling risk factors. CONCLUSION: There should
be more emphasis on developmental monitoring and appropriate intervention
programs for children to give them higher chance of having a more productive
life.
PMID- 28698724
TI - HLA-B*1502 in Iranian Children with Anticonvulsant Drugs-Induced Skin Reactions.
AB - OBJECTIVE: Anticonvulsant drugs can cause various forms of skin drug reactions,
ranging from exanthema to severe blistering reactions. An association between HLA
B*1502 allele and severe skin reactions have been reported. MATERIALS & METHODS:
Fifteen patients with severe skin reactions following treatment with
anticonvulsant drugs (Carbamazepine, lamotrigine, phenobarbital, primidone) and
15 controls (age-matched epileptic patients taking similar anticonvulsants
without drug eruption) were included. They were referred to Mofid Children's
Hospital in Tehran, Iran, between Jan 2012 to Jan 2014. Genomic DNA was extracted
from peripheral blood of all patients and HLA- B*1502 genotype was detected by
real-time PCR. RESULTS: None of the patients was positive for HLA- B*1502, but
two patients in control group had positive HLA- B*1502. CONCLUSION: The HLA-
B*1502 is not correlated with severe anticonvulsant drugs -induced skin reactions
in Iranian children.
PMID- 28698725
TI - Plasma Pyridoxal 5'-Phosphate Level in Children with Intractable and Controlled
Epilepsy.
AB - OBJECTIVE: Intractable epilepsy is a serious neurologic problem with different
etiologies. Decreased levels of pyridoxal phosphate in cerebral spinal fluid of
patients with intractable epilepsy due to pyridoxine dependency epilepsy are
reported. The aim of this study was to compare plasma pyridoxal 5'-phosphate
level in patients with intractable and controlled epilepsy. MATERIALS & METHODS:
This cross- sectional analytic study included 66 epileptic children, 33 patients
with controlled and 33 patients with intractable epilepsy, after neonatal period
up to 15 yr old of age. Thirty-three patients with intractable epilepsy (10- 162
months) and 33 patients with controlled epilepsy (14-173 months) were enrolled.
The study was conducted in Pediatric Neurology Clinic of Mofid Children Hospital,
Tehran, Iran from January 2010 to December 2010. Patients' clinical
manifestations, laboratory and neuroimaging findings were collected. Non-fasting
plasma 5'- pyridoxal phosphate levels of these subjects were assessed by high
pressure liquid chromatography. RESULTS: Mean plasma 5'- pyridoxal phosphate
level (PLP) in patients with controlled epilepsy was 76.78+/-37.24 (nmol/l) (15.5
232.4). In patients with intractable epilepsy, mean plasma 5'- pyridoxal
phosphate was 98.67+/- 80.58 (25.5- 393) nmol/l. There was no statistically
significant difference between plasma pyridoxal phosphate levels of these two
groups (P?0.430). CONCLUSION: Pyridoxine dependent epilepsy is under diagnosed
because it is manifested by various types of seizures. Plasma pyridoxal phosphate
levels did not differ in our patients with intractable or controlled epilepsy. If
PDE is suspected on clinical basis, molecular investigation of ALDH7A1 mutations,
as feasible test, until PDE biomarkers becomes available is recommended.
PMID- 28698726
TI - Clinical and Epidemiological Aspects of Multiple Sclerosis in Children.
AB - OBJECTIVE: Overall, 2%-5% of patients with multiple sclerosis (MS) experienced
the first episode of disease before the age 18 years old. Since the age of onset
among children is not similar to that in general population, clinicians often
fail to early diagnose the disease. This study aimed to determine the
epidemiological and clinical patterns of MS among Iranian children. MATERIALS &
METHODS: In this cross-sectional study carried out in Iran in 2014-2015,
information was collected using a checklist with approved reliability and
validity. Method sampling was consensus. Data were analyzed using frequency, mean
and standard deviation indices by means of SPSS ver. 20 software. RESULTS:
Totally, 177 MS children were investigated. 75.7% of them were female. Mean (SD),
minimum and maximum age of subjects were 15.9 (2), 7 and 18 yr, respectively. The
most reported symptoms were sensory (28.2%), motor (29.4%), diplopia (20.3%) and
visual (32.8%). Primary MRI results showed 91.5% and 53.1% periventricular and
spinal cord lesions, respectively. CONCLUSION: MS is significantly more common
among women. The most common age of onset is during the second decades. Sensory
and motor problems are the most symptoms, while, periventricular and spinal cord
lesions are the most MRI results.
PMID- 28698727
TI - Differences in Mean Platelet Volume and Platelet Count between Children with
Simple and Complex Febrile Seizures.
AB - OBJECTIVE: The aim of our study was to find the relationship of MPV (Mean
Platelet Volume) levels and platelet counts as markers of inflammation between
simple and complex febrile seizures. MATERIALS & METHODS: In this retrospective
comparative study, we investigated the recordings of 356 children between 5
months and 6 yr with diagnosis of simple and complex febrile seizure (SFS&CFS) in
Amircola's Children's Hospital, Babol University of Medical Sciences, Babol, Iran
between Mar 2011 and Dec 2015. RESULTS: Mean age was similar in two groups. The
MPV of the CFS group (8.32+/-0.48fl) was lower than that of the SFS group (8.58+/
0.34fl) but this difference was not significant statistically. The platelet count
of the CFS group (315.03*103 +/-117.17*103) was higher than that of SFS group
(291.82*103 +/- 87.49*103) but there was no significant statistical difference.
CONCLUSION: We did not find significant differences between two groups.
Therefore, further studies about this idea should be performed.
PMID- 28698728
TI - Association of 25-Hydroxyvitamin D Deficiency in Pediatric Epileptic Patients.
AB - OBJECTIVE: Epilepsy is a chronic neurological disorder requiring long-term
therapy using antiepileptic medications. Reports have incriminated long-term
antiepileptic drugs use in deficiency of vitamin D and bone diseases in all age
groups. We aimed to investigate the association between serum 25-hydroxyvitamin D
levels and pediatric epilepsy in Indian patients. MATERIALS & METHODS: We
prospectively recruited 100 pediatric epilepsy patients, on monotherapy for
minimum one-year duration, and 50 age and sex matched controls. This study was
carried out at Yashoda Hospital, India from 2011-2014. All cases and controls
underwent tests for serum 25-hydroxyvitamin D, alkaline phosphatase, serum
calcium and phosphorus levels. RESULTS: Patients with 25-hydroxyvitamin D
deficiency were significantly higher among cases (45%) than controls (24%). Mean
alkaline phosphatase was significantly higher in cases and mean serum calcium was
significantly lower (8.3+/-1.5) in cases. Amongst antiepileptic drugs,
carbamazepine and sodium valproate were significantly associated with 25
hydroxyvitamin D deficiency. Risk of vitamin D deficiency was highest with sodium
valproate usage (odds:4.0;95%CI 1.4-11.6) followed by carbamazepine use (odds:
2.7; 95%CI 1.0-6.8). After adjustment using multiple logistic regression,
antiepileptic drugs showed independent association with 25-hydroxyvitamin D
deficiency (odds:2.2;95%CI 0.9-4.5). CONCLUSION: 25-hydroxyvitamin D deficiency
was significantly associated with use of carbamazepine and sodium valproate in
pediatric epilepsy.
PMID- 28698729
TI - Neurological and Vascular Manifestations of Ethylmalonic Encephalopathy.
AB - Objective Ethylmalonic encephalopathy (EE) is a severe mitochondrial disease of
early infancy clinically characterized by a combination of developmental delay,
progressive pyramidal signs, and vascular lesions including petechial purpura,
orthostatic acrocyanosis, and chronic hemorrhagic diarrhea. Biochemical hallmarks
of the disease are persistently high level of lactate, and C4-C5-acylcarnitines
in blood, markedly elevated urinary excretion of methylsuccinic and ethylmalonic
(EMA) acids. Here we report two patients with EE as a 16-months-old male infant
and a 2-yr-old boy referred to Pediatric Neurology Clinic in Children's Medical
Center, Tehran-Iran that in one patient genetic analysis revealed a homozygous
mutation of the ETHE1 gene in favor of ethylmalonic acidemia.
PMID- 28698730
TI - Neurobrucellosis Presenting with Unilateral Abducens Nerve Palsy.
AB - One of the rare complications of brucellosis is neurobrucellosis. There have been
numerous reports showing clinical forms of brucellosis affecting CNS, such as
cranial nerve involvement, myelitis, vascular disease, radiculoneuritis,
meningitis, meningoencephalitis, and demyelinating disease. In this case report,
we introduce a 2.5 yr old girl with unilateral abducens nerve palsy referred to
Baghiyatallah Hospital Outpatient Clinic, Tehran, Iran in June 2015.
PMID- 28698731
TI - Intermittent Hemiplegia in a Boy with Primary Moyamoya Disease: A Case Report
from Iran.
AB - Moyamoya is a rare chronic progressive occlusive cerebrovascular disease. Its
manifestation varies from stroke, progressive learning impairment and transient
ischemic attack to headache and seizure. There is no accepted medical treatment
and surgery usually, is needed. We report here a case of 8 yr old boy referred to
psychiatrist outpatient. An eight yr old boy with intermittent hemiplegia was
brought to Imam Ali Clinic, Yazd, Iran in 2015 because his headache and medical
problem began from 6 yr old. Stress and excitement exacerbated his condition. His
first attack was at the age of 6 yr old. During attack, he had incontinence,
severe headache, alogia, pallor, claudication and left hemiplegia (Left lower
limb). Magnetic resonance angiography (MRA) was done and our diagnosis was
moyamoya disease. Moyamoya is a mysterious disease and psychiatrists should
consider it in differential diagnosis of alogia and plegia. Acute management of
this disease is mainly symptomatic. Nowadays, surgery is a good choice and early
diagnosis of this disease can change our patient's life.
PMID- 28698732
TI - Tumefactive Multiple Sclerosis Variants: Report of Two Cases of Schilder and Balo
Diseases.
AB - A tumefactive lesion of central nervous system (CNS) is defined as a mass-like
lesion with a size greater than 2 cm in brain detected by magnetic resonance
imaging (MRI). Neuroimaging may help to distinguish the nature of a tumefactive
lesion and therefore, can prevent an unnecessary brain biopsy. Here we emphasized
on determining the nature of a CNS tumefactive lesions with the help of MRI and
more explanations about demyelinating lesions with focus on Schilder and Balo
diseases as two multiple sclerosis variants. We have reported here two boys of 10
and 8 years of age respectively of multiple sclerosis (MS) variants who presented
with acute neurologic complications to our hospital as one of the two referral
children hospital in Tehran, Iran. Tumefactive demyelinating lesions can be
considered a separate entity that itself can contain Schilder disease, Balo
disease, some cases of acute disseminated encephalomyelitis (ADEM) or classic MS.
MRI can help to establish a diagnosis of a tumefactive lesion and to
differentiate among different underlying etiologies.
PMID- 28698733
TI - Chronic Renal Failure Secondary to Unrecognized Neurogenic Bladder in A Child
with Myelodysplasia.
AB - Myelodysplasia includes a group of developmental anomalies resulting from defects
that occur during neural tube closure. Urological morbidity in patients with
myelodysplasia is significant and if not treated appropriately in a timely manner
can potentially lead to progressive renal failure, requiring dialysis or
transplantation. We report the case of a 13-year old girl with neurogenic bladder
who presented chronic renal failure secondary to lipomyelomeningocele with
retethering of cord. She was managed with urinary indwelling catheterization
until optimization of renal function and then underwent detethering of cord with
excision and repair of residual lipomeningomyelocele. Her renal parameters
improved gradually over weeks and then were managed on self clean intermittent
catheterization. The case emphasizes the need for considering retethering of
spinal cord in children with myelodysplasia where symptoms of neurogenic bladder
and recurrent urinary tract infections occur.
PMID- 28698734
TI - Methods of Biotyping of Streptococcus mutans Species with the Routine Test as a
Prognostic Value in Early Childhood Caries.
AB - PURPOSE: In order to investigate the suitability of Streptococcus mutans species
biotyping by measuring the activity of selected enzymes from a commercial test,
criteria were established for biotyping clinical strains from children with
dental caries. In addition, the relationships between the selected biotypes,
sensitivity to commonly used antibiotics, and early childhood caries were
determined. METHODS: A total of 142 S. mutans isolates from dental plaque of
children with caries were divided into different biotypes. Patients were divided
into two groups: noncavitated (1-2 in ICDAS) and cavitated (5-6 in ICDAS)
lesions. Biotyping criteria were determined based on both the arbitrary method
and the clusterization method. The susceptibility of the strains to amoxicillin,
cefazolin, erythromycin, and teicoplanin was studied by diluting a solid medium.
RESULTS: Biotype I was the most common. Mean MIC values showed that the strains
belonging to biotypes II and IV were the most sensitive to amoxicillin. For
predetermined biotypes, observed differences were dependent on the severity of
dental caries. CONCLUSIONS: The proposed method of S. mutans strains biotyping is
relatively quick and simple to use, provided the application of suitable
biotyping criteria, and may contribute to the effective prevention of dental
caries induced by S. mutans.
PMID- 28698735
TI - Cardioprotection against Heart Failure by Shenfu Injection via TGF-beta/Smads
Signaling Pathway.
AB - OBJECTIVE: To explore the potential cardioprotective mechanism of Shenfu
injection (SFI) against heart failure (HF) by attenuating myocardial fibrosis and
cardiac remodeling. METHODS AND RESULTS: Four weeks after myocardial infarction
(MI), adult male Sprague Dawley rats were randomized for 4-week treatment with
Valsartan, SFI, or vehicle. Echocardiography and hemodynamics were applied to
evaluate cardiac functions. Myocardia of coronary artery ligated (CAD) rats were
observed to investigate changes in cardiac structure and function. Our findings
suggest that treatment with SFI could inhibit progression of myocardial fibrosis
and attenuate cardiac remodeling. In addition, SFI decreased expression of Smad2
and Smad3, while increasing the expression of Smad7 through regulation of TGF
beta/Smads signaling pathway. CONCLUSION: Treatment with SFI in Sprague Dawley
rats improves ventricular structure and function and reduces cardiac fibrosis by
ameliorating TGF-beta/Smads signaling pathway after ventricular remodeling.
PMID- 28698736
TI - Draft Genome Sequence of the Symbiotic Frankia Sp. Strain KB5 Isolated from Root
Nodules of Casuarina equisetifolia.
AB - Frankia sp. strain KB5 was isolated from Casuarina equisetifolia and previous
studies have shown both nitrogenase and uptake hydrogenase activities under free
living conditions. Here, we report 5.5-Mbp draft genome sequence with a G+C
content of 70.03 %, 4,958 candidate protein-encoding genes, and 2 rRNA operons.
PMID- 28698737
TI - Draft Genome Sequence of a Virulent Strain of Pasteurella Multocida Isolated From
Alpaca.
AB - Pasteurella multocida is one of the most frequently isolated bacteria in acute
pneumonia cases, being responsible for high mortality rates in Peruvian young
alpacas, with consequent social and economic costs. Here we report the genome
sequence of P. multocida strain UNMSM, isolated from the lung of an alpaca
diagnosed with pneumonia, in Peru. The genome consists of 2,439,814 base pairs
assembled into 82 contigs and 2,252 protein encoding genes, revealing the
presence of known virulence-associated genes (ompH, ompA, tonB, tbpA, nanA, nanB,
nanH, sodA, sodC, plpB and toxA). Further analysis could provide insights about
bacterial pathogenesis and control strategies of this disease in Peruvian
alpacas.
PMID- 28698738
TI - Complete Genome Sequence and Comparative Genomics of a Streptococcus pyogenes
emm3 Strain M3-b isolated from a Japanese Patient with Streptococcal Toxic Shock
Syndrome.
AB - Epidemiologic typing of Streptococcus pyogenes (GAS) is frequently based on the
genotype of the emm gene, which encodes M/Emm protein. In this study, the
complete genome sequence of GAS emm3 strain M3-b, isolated from a patient with
streptococcal toxic shock syndrome (STSS), was determined. This strain exhibited
99% identity with other complete genome sequences of emm3 strains MGAS315, SSI-1,
and STAB902. The complete genomes of five additional strains isolated from
Japanese patients with and without STSS were also sequences. Maximum-likelihood
phylogenetic analysis showed that strains M3-b, M3-e, and SSI-1, all which were
isolated from STSS patients, were relatively close.
PMID- 28698739
TI - Complete Genome Sequence of Actinomadura Parvosata Subsp. Kistnae, A Rich Source
of Novel Natural Product (Bio-)Chemistry.
AB - The soil dwelling actinomycete strain Actinomadura parvosata subsp. kistnae is
the producer of the antiviral antibiotics kistamicin A and B. Genome sequencing
and bioinformatic analysis revealed the presence of the kistamycin biosynthetic
gene cluster responsible for the formation of these non-ribosomal peptides as
well as an impressive number of yet uncharacterized biosynthetic pathways. This
includes polyketide, ribosomal and non-ribosomal peptide and a large number of
terpenoid biosynthetic loci encoding yet unknown natural products. The genomic
data of this strain is thus a treasure trove for genome mining for novel
functional metabolites and new biocatalysts.
PMID- 28698740
TI - The Correlation between Body Mass Index with the Occurrence of Skin Tag.
AB - BACKGROUND: Skin tag is a benign tumour of the skin with a soft consistency which
commonly occurs in the flexure area. Skin tag often found in individuals with
middle and old age. Until now, there are many of theories have been proposed to
explain the mechanism of the skin tag, one of the theory is obesity. AIM: To
determine the body mass index (BMI) in patients with skin tag. METHODS: This
study is an analytic study with cross-sectional designs involving 32 subjects
with skin tag and 32 controls. Diagnosis of skin tag was made based on anamnesis
and clinical examination. All subjects underwent a physical examination (height
and weight) to determine BMI (weight in kilogrammes divided by the square of
height in meters). To analyse association between higher BMI with the occurrence
of skin tag we use student t-test. RESULTS: The mean BMI in the skin tag group
(28.1+ 3.9 kg/m^2) was higher compared with the control group (24.1 + 2.3
kg/m^2). Statistical analysis by Student t-test found the p-value < 0.05.
CONCLUSION: We found a correlation between increased BMI with the occurrence of
the skin tag.
PMID- 28698741
TI - Association of the Pro12Ala Polymorphism with the Metabolic Parameters in Women
with Polycystic Ovary Syndrome.
AB - AIM: To investigate the association of peroxisome proliferator-activated receptor
gamma (PPARG) Pro12Ala polymorphism with polycystic ovary syndrome (PCOS) and its
effect on the metabolic parameters in PCOS women. METHODS: The study used PCR to
identify the presence of the PPARG Pro12Ala polymorphism in 100 PCOS women and
120 age-matched healthy women. All participants were subjected to anthropometry,
biochemical and metabolic evaluation. RESULTS: Significant difference in the
genotypes distributions of PPARG Pro12Ala polymorphism was observed among PCOS
women and controls (p = 0.03). The frequency of the polymorphic allele Ala was
significantly higher in PCOS cases than that in the controls (OR = 2.01, p =
0.01). The carries of the variant allele Ala in PCOS women showed significant
higher values in body mass index (BMI), systolic and diastolic blood pressure,
waist circumference, waist to hip ratio, sum of skin folds, fasting blood
glucose, fasting blood insulin, HOMA-IR, fasting triglycerides, total cholesterol
and low-density lipoprotein than non-carriers. CONCLUSION: The PPARG Pro12Ala
polymorphism might contribute to the risk of PCOS and abnormal metabolic
parameters and could be considered as a biomarker for early diagnosis and clinic
prediction of metabolic complications.
PMID- 28698742
TI - In Vitro Nematophagous Activity of Predatory Fungi on Infective Nematodes Larval
Stage of Strongyloidae Family.
AB - AIM: The main goal of the present research conducted to assess the in vitro
activity of the nematophagous fungi Duddingtonia flagrans, Fusarium solani,
Verticillium chlamidosporium, and Trichoderma harzianum. MATERIAL AND METHODS:
Four isolates of fungi including D. flagrans, F. solani, V. chlamidosporium and
T. harzianum were used in this study. Horse faeces were used to provide the
larvae stage of Strongyloidae family for the experiments. RESULTS: D. flagrans
was the most effective fungus to reduce the population of the larval nematodes.
D. flagrans was able to kill 100% of larvae after 14 days of incubation. The
significant effect was seen after 7 days of incubation, therefore, the live
larvae was decreased to 9, 11, 19 and 25 for D. flagrans, V. chlamidosporium, F.
solani and T. harzianum, respectively. CONCLUSION: Our results illustrated that
D. flagrans were most successful fungus for reducing the number of Strongylidae
family larva stage from horse faeces. Follow D. flagrans, the live larvae was
significantly reduced for V. chlamidosporium, F. solani and T. harzianum,
respectively.
PMID- 28698743
TI - Higher Rate of Iron Deficiency in Obese Pregnant Sudanese Women.
AB - AIM: To assess the association between obesity and iron deficiency (ID). MATERIAL
AND METHODS: Pregnant women were recruited from Saad Abualila Hospital, Khartoum,
Sudan, during January-April 2015. Medical history (age, parity, gestational age)
was gathered using questionnaire. Weight and height were measured, and body mass
index (BMI) was calculated. Women were sub-grouped based on BMI into underweight
(< 18.5 kg/m^2), normal weight (18.5-24.9 kg/m^2), overweight (25-29.9 kg/m^2)
and obese (>= 30 kg/m^2). Serum ferritin and red blood indices were measured in
all studied women. RESULTS: Two (0.5%), 126 (29.8%), 224 (53.0%) and 71 (16.8%)
out of the 423 women were underweight, normal weight, overweight and obese,
respectively. Anemia (Hb <11 g/dl), ID (ferritin <15ug/l) and iron deficiency
anemia (IDA) were prevalent in 57.7%, 21.3% and 12.1%, respectively. Compared
with the women with normal BMI, significantly fewer obese women were anemic [25
(35.2%) vs. 108 (85.7%), P < 0.001] and significantly higher number of obese
women [25 (35.2) vs. 22 (17.5, P = 0.015] had iron deficiency. Linear regression
analysis demonstrated a significant negative association between serum ferritin
and BMI (- 0.010 ug/, P= 0.006). CONCLUSION: It is evident from the current
findings that prevalence of anaemia and ID showed different trends about BMI of
pregnant women.
PMID- 28698744
TI - Outcome of Cardiac Rehabilitation Following Off-Pump Versus On-Pump Coronary
Bypass Surgery.
AB - BACKGROUND: A few studies have compared the cardiac rehabilitation (CR) outcome
between those who undergo conventional on-pump bypass surgery and off-pump
surgery. We compared this outcome among the patients differentiated by the On
pump and off-pump surgical procedures about cardiovascular variables and
psychological status. METHODS: This longitudinal study recruited 318 and 102
consecutive patients who had undergone CABG (on-pump surgery, n = 318 and off
pump surgery, n = 102) and been referred to the CR clinic. RESULTS: The off-pump
surgery patients had more improvement in their metabolic equivalents (METs)
value. The physical and mental components of health-related quality of life (QOL)
(based on SF-36 questionnaire) as well as depression-anxiety (based on Costello
Comrey Depression and Anxiety Scale) were notably improved in the two study
groups after the CR program, while changes in the QOL components scores and also
depression-anxiety score were not different between the off-pump and on-pump
techniques. CONCLUSIONS: Regarding QOL and psychological status, there were no
differences in the CR outcome between those who underwent off-pump bypass surgery
and those who underwent on-pump surgery; nevertheless, the off-pump technique was
superior to the on-pump method on METs improvement following CR.
PMID- 28698745
TI - New Surgical Technologies Could Facilitate Surgical Hemostasis in Hemophilic
Patients.
AB - BACKGROUND: It's assumed that surgery in haemophilia can be accomplished these
days safely. AIM: The aim of this study was to investigate the influence of new
surgical technologies in the perioperative management and outcome of surgical
procedures in haemophiliacs. METHODS: Two patients with mild haemophilia A
underwent surgery (laparoscopic appendectomy and inguinal hernia repair). In both
patients, the replacement therapy, with factor VIII, started 30 min before
surgery. We used the available surgical technologies and techniques with a proven
value in the best clinical practice, to achieve proper and permanent hemostasis.
Postoperatively, the replacement therapy and thromboembolic prophylaxis was
continued according to the international guidelines for the management of
haemophilia. RESULTS: The operative and post-operative periods were uneventful.
No significant differences were found in the operation time in our hemophilic
patients versus non-hemophilic patients. Significant differences related to the
hospital stay duration were found in both patients compared with controls, due to
the necessary replacement therapy. CONCLUSION: With new surgical technologies,
proper and permanent hemostasis can be achieved, without prolonging the operation
time.
PMID- 28698746
TI - Study of Visfatin Level in Type 1 Diabetic Children and Adolescents.
AB - BACKGROUND: Visfatin is an intracellular enzyme, known as nicotinamide
phosphoribosyltransferase (Nampt) and pre-B-cell colony-enhancing factor (PBEF
1). It has insulin-mimetic effects and lowers plasma glucose levels. AIM: The aim
of the work was to assess serum concentration of Visfatin in type 1 diabetic
children and adolescents and study its relationships with duration of diabetes,
body mass index (BMI), glycemic control, insulin dosage, lipid profile and
microvascular complications. MATERIAL AND METHODS: Fifty children and adolescents
with type 1 diabetes mellitus were recruited with 30 ages and gender-matched
healthy subjects. They were subjected to history taking; anthropometric
measurements and chronic diabetic complications were recorded if present.
Laboratory analysis included urinary microalbumin, serum triglycerides, HDL, LDL,
cholesterol, fasting blood glucose, glycosylated Hb (HbA1c) and serum visfatin
which was measured with enzyme-linked immunosorbent assay. RESULTS: Diabetic
patients showed highly significant decrease in the level of visfatin compared to
the control group (P = 0.0001). There was significant further decrease in
visfatin level in diabetics with microalbuminuria (n = 13) compared to
normoalbuminuric patients (n = 37) (P = 0.015). There was highly significant
inverse correlation between visfatin level with age (r = -0.379, p = 0.007), BMI
(r = -0.418, p = 0.003), waist circumference (r = -0.430, p = 0.002), hip
circumference (r = -0.389, p = 0.005) and microalbuminuria (r = -0.323, p =
0.022). CONCLUSIONS: Type 1 diabetic children and adolescents had a significantly
lower visfatin level compared to controls. A marked decrease in the level of
visfatin was shown in patients with microalbuminuria with an inverse correlation
with BMI suggesting an important role of visfatin in the pathogenesis of type 1
diabetics and type 1 diabetic nephropathy.
PMID- 28698747
TI - Association among Thyroid Dysfunction, Asthma, Allergic Rhinitis and Eczema in
Children with Alopecia Areata.
AB - BACKGROUND: Alopecia areata is a non-scarring hair loss, which typically starts
quickly. Atopy is one of the possible predisposing risk factors for this
condition. AIM: This study aimed to evaluate the prevalence of thyroid disease,
atopic dermatitis and allergic diseases in children with alopecia areata and
compare the results with healthy individuals. METHODS: This case-control study
was conducted on 50 patients with alopecia areata, diagnosed by a dermatologist,
and 150 healthy individuals as the control group. Participants filled the
questionnaires, and necessary tests were performed. RESULTS: In this study, the
mean age of the participants was 2.55 +/- 14.26 and 3.19 +/- 11.92 in the case
and control groups, respectively. Prevalence of asthma was 22% in the case group
and 12.5% in control group (P = 0.109). Also, allergic rhinitis and eczema were
observed in 20% and 22% of the subjects of the case group, whereas they were
reported to be 8% and 10% in the control group (PV = 0.03 and 0.175,
respectively). Moreover, 28% and 8% of the participants in the case and control
groups had a family history of atopy and allergic disorders, respectively (P =
0.046). A significant difference was observed between the two groups regarding
gender, type of delivery and contact with animals. CONCLUSIONS: According to the
results of this study, a significant association was observed between the
prevalence of alopecia areata and atopic conditions, such as allergic rhinitis
and history of atopic dermatitis.
PMID- 28698748
TI - Acute Postoperative Pain in Trauma Patients - The Fifth Vital Sign.
AB - AIM: To determine average pain intensity perceived by trauma patients at hospital
admission, lowest and highest pain intensity during their hospitalisation and
their satisfaction with provided pain treatment. PATIENTS AND METHODS: The
research included 114 operated patients at the Clinical Department of Trauma
Surgery. We used the standard Numerical Rating Scale (NRS) for a clinical measure
of pain. RESULTS: The average pain intensity at hospital admission was NRS median
7 (range 4-10), the severest perceived rate of pain during hospitalisation was
NRS median 5 (range 4-7). Ninety-four percent of our respondents were satisfied
with provided pain treatment. Thirty-two percent of patients were not asked to
assess their pain during their hospitalisation, and 40.4% of patients assessed
their pain occasionally. CONCLUSION: Female patients, as well as patients
admitted to the emergency department, reported higher NRS scores. Those
respondents who perceived severe pain answered more often that medical staff
didn't ask them to assess their pain on any occasion. Good communication between
medical staff and patients, together with adequate assessment and evaluation of
acute pain are of great importance in its treatment.
PMID- 28698749
TI - The Role of Sleeve Gastrectomy on Preventing Type 2 Diabetes Mellitus.
AB - AIM: To investigate the effect of bariatric surgery on HbA1c and serum cortisol
levels in morbidly obese patients without type 2 diabetes mellitus. MATERIALS AND
METHODS: Twenty-nine patients who underwent sleeve gastrectomy and whose body
mass index was> 40 were included in the present study. Patients' files were
reviewed retrospectively. Those with diabetes mellitus and those with age <18
were excluded from the study. Pre-operative and 1-year post operative data were
documented. The obtained data were analysed by SPSS statistical program. RESULTS:
The mean age of the patients was 27.4 +/- 8.4. 5 of the patients were male, and
24 were female. The mean body mass index of the patients was 44 +/- 2.3. 1
patient [3.4%] had hypertension. Four patients [13.7%] had gastroesophageal
reflux disease. The number of smokers was 7 [24.1%], and the number of alcohol
users was 3 [10.3%]. There was a statistically significant decrease in HbA1c,
body mass index values after operation [p value <0.01], but cortisol was not
different [p value = 0.72]. CONCLUSION: In this present study we found that
bariatric surgery caused a significant decrease in HbA1c levels in non-diabetic
patients, suggesting that bariatric surgery may prevent Type 2 Diabetes Mellitus
in obese patients.
PMID- 28698750
TI - The Relationship between Risk Factors of Head Trauma with CT Scan Findings in
Children with Minor Head Trauma Admitted to Hospital.
AB - BACKGROUND: In emergency medicine for determining the intracranial injury (ICI)
in children with head trauma, usually brain CT scan is performed. Since brain CT
scan, especially in children, has some disadvantages, it is better to find a
procedure which could help to choose only the children with real head trauma
injury for brain CT scan. AIMS: The aim of this study is to find such procedure.
This study was descriptive, analytic and non-interventional. METHODS: We reviewed
the archived files of children with head trauma injuries referred to the
emergency department of Imam Hossein Hospital within two years. Patient's CT scan
findings and head trauma risk factors were evaluated in this study. RESULTS: Out
of 368 patients, 326 patients had normal brain CT scan. 28 of them showed
symptoms of ICI consisting intraventricular haemorrhage (IVH), contusion,
subarachnoid haemorrhage (SAH), subdural haemorrhage (SDH), epidural hematoma
(EDH), and pneumocephalus. Twenty-seven patients showed skull FX, which 14 of
them had an Isolated fracture, and 13 of them also showed symptoms of ICI. Since
patients with isolated FX usually discharge quickly from Emergency Department;
their data did not include in results of the study. The patients have been
divided into two groups: 1- ICI, 2- without ICI. RR (relative risk), CI
(Confidence interval) and sensitivity, positive predictive value (PPV), negative
predictive value (NPV) and association of these risk factors with ICI were
assessed with the Chi-2 test. In the end to determine the indications of CT scan,
the presence of one of these five risk factors is important including abnormal
mental status, clinical symptoms of skull FX, history of vomiting, craniofacial
soft tissue injury (including subgaleal hematomas or laceration) and headache.
CONCLUSIONS: For all other patients without these risk factors, observation and
Follow Up can be used which has more advantages and less cost.
PMID- 28698751
TI - Analysis of Factors that Influence Hematopoietic Recovery in Autologous
Transplanted Patients with Hematopoietic Stem Cells from Peripheral Blood.
AB - BACKGROUND: Successful hematopoietic stem cell transplantation (HSCT) requires a
rapid and durable hematopoietic recovery. AIM: The aim of our study was to
analyse factors that influence hematopoietic recovery after autologous HSCT.
MATERIALS AND METHODS: Multiple regression analysis was used to analyse factors
affecting neutrophil and platelet engraftment in 90 autologous transplanted
patients - 30 with acute myeloid leukaemia (AML), 30 with lymphoma and 30 with
multiple myeloma (MM) from 2008 till 2016. RESULTS: The neutrophil recovery in
AML patients was significantly influenced by transfusion support with random
donor platelets, sex and number of transplanted mononuclear cells (MNC) and CD34+
cells; and in lymphoma patients, it was influenced by sex, age, mobilisation
strategy and some transplanted MNC. The influence of investigated factors on
neutrophil engraftment in MM patients was not statistically significant. The
platelet recovery in AML patients was influenced by transfusion support with
random-donor platelets; in lymphoma patients, it was influenced by sex, age, time
from diagnosis to harvesting and time from diagnosis to HSCT; and in MM patients
it was influenced by transfusion support with random-donor platelets. CONCLUSION:
Additional studies are necessary to better understanding of engraftment kinetic
to improve the safety of HSCT and to minimise potential complications and
expenses related to HSCT.
PMID- 28698752
TI - Correlation between Serum Homocysteine and Vitiligo Area Scoring Index.
AB - BACKGROUND: Vitiligo is a chronic skin disorder. White macules caused by
melanocyte destruction is a characteristic finding that cosmetically disturbing.
Until recently, pathogenesis of vitiligo is still unclear. The role of
homocysteine in vitiligo is mentioned in previous studies thus it is probable
that it can be a biomarker to determine vitiligo severity. AIM: To determine
correlation between serum homocysteine and vitiligo area Scoring Index (VASI).
SUBJECT AND METHOD: This was a cross-sectional analytic study which involved 30
vitiligo patients that were diagnosed by clinical and Wood's lamp examinations
then VASI score was determined and same numbers of control. We conducted blood
sampling and measurement of serum homocysteine level to the patients. RESULTS:
There is no significant correlation between serum homocysteine and VASI score (p
= 0.133, r = 0.281), family history (p = 0.706), and duration of vitiligo (p =
0.993, r = 0.002). There is no significant difference between serum homocysteine
in vitiligo patients and controls (p = 0.905). There is a correlation between
serum homocysteine with gender (p = 0.001) and age (p = 0.036; r = 0.385) in
vitiligo patient. CONCLUSION: There is no significant correlation between serum
homocysteine and VASI score, family history, and duration of vitiligo. There is
no significant difference between serum homocysteine in vitiligo patients and
controls. There is a correlation between serum homocysteine with gender and age
in vitiligo patient.
PMID- 28698753
TI - Comparison of Diagnostic Value of Sonourethrography with Retrograde Urethrography
in Diagnosis of Anterior Urethral Stricture.
AB - BACKGROUND: In spite of the advanced imaging methods, MRI and CT-Scan, the role
of ultrasonography is still unique in some fields of genitourinary tract
diseases. AIM: This study was aimed at assessing this role in the evaluation of
male urinary stricture, and comparison with standard retrograde urethrography
(SUG). METHODS: This was a cross-sectional study. The patients include those who
were suspected of anterior urethral stricture and were introduced assessed with
imaging techniques (RUG). The patient underwent ultrasonography too. The results
of both methods were compared. RUG was considered as the gold standard for this
comparison. RESULT: Ninety-seven patients were studied. The mean age was 46.9 +/-
11.7 years (range 21-88 years), in RUG, 22 patients (22.8%) and SUG 23 patients
(23.7%) had a stricture, 3 cases with a stricture in RUG had not evidenced of
stenosis in SUG. The mean length of urethral stricture in RUG was 12.9 +/- 8.1 mm
and in SUG was 8.1 +/- 7.3 mm. The estimated length in RUG way was significantly
higher than SUG way (P=0.025). The sensitivity and specificity in using of SUG
were 86.6% and 94.6%, respectively. CONCLUSION: The result of this study showed
stricture length measured by ultrasound is shorter than the length measured by
RUG and the sensitivity and specificity in using of SUG was 86.6% and 94.6%
respectively that due to the advantages it is an acceptable way.
PMID- 28698754
TI - Early and Late Complications in Patients with Allogeneic Transplantation of
Hematopoietic Stem Cell - Case Report.
AB - BACKGROUND: Allogeneic hematopoietic stem cells transplantation (HSCT) is a
curative intervention in patients with haematological malignant and non-malignant
diseases, immunodeficiency, autoimmune, and other genetic diseases. Early
complications are complications that are occurring in the first 100 days, while
complications arising after the 100th day of transplantation belong to late
complications. CASE REPORT: Forty-nine years old patient with AML treated with
allogeneic HSCT from HLA-identical (sister) donor. Ascertained and display of
early (acute Graft versus host disease (GvHD) and late complications (chronic
GVHD, infections, cataract, secondary malignancy with MS deposits) are made, that
emerged after the patient transplantation. CONCLUSION: Rapidly growing population
of patients that undergo allogeneic HSCT creates an obligation to educate
patients and physicians about observed late complications that occur after this
therapy.
PMID- 28698755
TI - Primary Fallopian Tube Carcinoma: A Case Report and Literature Review.
AB - BACKGROUND: Primary fallopian tube carcinoma (PFTC) is a rare tumour of the
female genital tract with an incidence of 0.1-1.8% of all genital malignancies,
and it is very difficult to diagnose preoperatively, because of its non-specific
symptomatology. In most cases, it is an intraoperative finding or a
histopathological diagnosis. It is a tumour that histologically and clinically
resembles epithelial ovarian cancer. CASE PRESENTATION: We are reporting a case
of a 62-year-old, postmenopausal women with primary fallopian tube carcinoma of
the right fallopian tube in stage IA. The patient has lower abdominal pain,
watery vaginal discharge and repeated episodes of bleeding from the vagina. The
clinical and radiological findings suggested a right adnexal tumour with elevated
CA-125 levels. Total abdominal hysterectomy, bilateral salpingo-oophorectomy,
omentectomy and peritoneal washing were performed. Pathologic confirmation of
primary serous cystadenocarcinoma of the right fallopian tube was made.
Peritoneal washings were negative for malignancy. FIGO stage was considered as
IA, and the patient received no courses of chemotherapy and postoperative
radiation because she refused it. Ten months after initial surgery, the patient
is alive and in good condition. CONCLUSION: Cytoreduction surgery followed by
adequate cycles of chemotherapy is an important strategy to improve patients'
prognosis.
PMID- 28698756
TI - Treatment of Decubitis Ulcer Stage IV in the Patient with Polytrauma and Vertical
Share Pelvic Fracture, Diagnosed Entherocollitis and Deep Wound Infection with
Clostridium Difficile with Combined Negative Pressure Wound Therapy (NPWT) and
Faecal Management System: Case Report.
AB - AIM: The aim of this paper was to present a case with the successful treatment of
decubitis ulcer stage IV in the patient with polytrauma and vertical share pelvic
fracture and diagnosed entherocollitis combined with deep wound infection with
Clostridium difficile treated with combined Negative Pressure Wound Therapy
(NPWT) and faecal management system. CASE REPORT: Patient D.S.1967 treated on
Traumatology Clinic after tentamen suicide on 9.2.2015 with diagnosis: brain
contusion; contusion of thoracal space; vertical share pelvic fracture; open
fracture type II of the right calcaneus; fracture of the left calcaneus; fracture
on the typical place of the left radius; fracture of the right radius with
dislocation. As a first step during the treatment in Intensive care unit we
perform transcondylar extension of the left leg, and in that time we cannot
operate because of the brain contusion. Four weeks after this treatment we intent
to perform stabilisation of the pelvic ring, fixation of both arms, and fixation
of both calcanear bones. But at the time before performing the saurgery, the
patient got an intensive enterocollitis from Escherichia colli and Clostridium
difficile, and during the inadequate treatment of enterocollitis she got a big
decubitus on both gluteal regia Grade IV and deep muscular necrosis. Several
times we perform a necrectomy of necrotic tissue but the wound become bigger and
the infection have a progressive intention. In that time we used VAK system for 6
weeks combined with faecal management system and with local necrectomy and system
application of Antibiotics and Flagyl for enterocollitis in doses prescripted
from specialists from Infective clinic. This new device to manage faecal deep
decubital infection and enterocollitis with Clostridium difficile are considered
as adequate. 8Flexi-Seal(r) FMS has been also used. After two months we succeed
to minimize the gluteal wound on quoter from the situation from the beginning and
we used for next two months wound treatment from Departement for Plastic and
Reconstructive Surgery. CONCLUSION: When faecal incontinence as a result of
enterocollitis with Clostridium difficile does occur, a limiting contact with the
patient's skin is extremely important as breakdown can occur rapidly. In addition
to tissue injury, faecal incontinence can have a major impact on the patient's
dignity and result in prolonged hospital stay. The main outcomes assested in the
case studies were resolution of of decubital ulcers as a result of faecal
incontinence, patient comfort and ease of application of the FMS and NPWT. The
soft flexible catheter was easily inserted without discomfort to the patients. It
gently conformed to the rectal vault, reducing significantly the risk of
necrosis, and the risk for prolonged necrosis in cases with previously developed
necrosis. FMS was successful in diverting faecal fluid away from the perineal
tissue and resolved any decubitus ulcer developed previously in combination with
use of NPWT. So, we can recommend this combination in those cases especially with
polytraumatismus, vertical share pelvis fracture combined with diarrhea and deep
wound infection of decubital ulcers Grade IV infected with Cl. difficile.
PMID- 28698757
TI - New Safety Margins for Melanoma Surgery: Nice Possibility for Drinking of "Just
That Cup of Coffee"?
AB - BACKGROUND: The American Joint Committee on Cancer (AJCC's) skin melanoma
surgical treatment recommendations from 2011 are characterised by a prima facie
"freedom of choice" regarding how extensive should be the excisions for melanomas
with tumour thickness up to 2 mm and melanoma in situ. It is unclear why the
recommended surgical security margins vary between 0.5 and 1 cm for melanoma in
situ, whereas for melanomas with a tumour thickness of up to 1.99 mm, the range
of variation is also between 1 and 2 cm, without specifying when the surgical
field should be broader and, narrower, accordingly. This "uncertainty or lack of
intent" of the guilders often leads to the same surgical approach to melanomas at
different stages, or to a different approach in cases of melanomas at the same
stage, in contrast. Therefore, this should be defined as wrong, logically. CASE
PRESENTATION: We present 3 patients with cutaneous melanomas, treated with
similar fields of surgical security. Current issues, generated within the
framework of melanoma's surgery guided by the recommendations of the AJCC are
also discussed. A new surgical approach in patients with melanoma is recommended,
discussed for the first time in world literature. We hypothesize that the
introduction of a certain recommendations for a 2 cm surgical field in all
directions during the initial excision, combined with the parallel performance of
a sentinel lymph node biopsy, will lead in fact to several important advantages:
1) avoiding of the secondary excision in at least 70% - 90% of the patients
(depending on the tumor thickness), 2) minimizing the risk of lymphatic effusion
change and misinterpretation of the sentinel lymph node biopsy's results in
patients with secondary excision; 3) optimization of the surgical team's work; 4)
minimizing the possibility of unprepared/uninformed personnel to take part in
decisions for treating a specific disease such as skin melanoma, 4) facilitating
the appropriate patients' group selection at the appropriate stage when involving
them in different studies, leading to equal leveling of the initial positions.
CONCLUSION: Whether the proposed approach will be subjected to a detailed
discussion of AJCC's expert's remains currently unclear.
PMID- 28698758
TI - Maxillary Sinus Augmentation Using a Titanium Mesh: A Randomized Clinical Trial.
AB - BACKGROUND: Various attempts have been implemented using different materials and
techniques to augment the maxillary sinus floor for prospect dental implant
positioning. AIM: This contemplate was conducted to assess the osteogenic
capability of the maxillary sinus in a two-step sinus membrane elevation using
titanium mesh to keep the formed space to place dental implants in atrophic
ridges. MATERIALS AND METHODS: Titanium micromesh was customized and positioned
into the sinus on one side to preserve the elevated membrane in position. On the
other side xenograft was applied. Instant and 6-months postoperative cone beam
computed tomography (CBCT) was done to assess the gained bone height and density.
Bone core biopsies were obtained during implant placement for histological and
histomorphometric evaluation. RESULTS: The average bone height values increased
in both groups. Meanwhile the average bone density value was higher at the graft
group than the titanium mesh group. Histological and histomorphometric evaluation
presented the average bone volume of the newly formed bone in the graft group
which is superior to that of the titanium mesh group. CONCLUSION: The use of the
titanium micromesh as a space-maintaining device after Schneiderian membrane
elevation is a trustworthy technique to elevate the floor of the sinus without
grafting.
PMID- 28698759
TI - Effect of Free Maternal Health Care Program on Health-seeking Behaviour of Women
during Pregnancy, Intra-partum and Postpartum Periods in Cross River State of
Nigeria: A Mixed Method Study.
AB - BACKGROUND: Increasing the percentage of maternal health service utilization in
health facilities, through cost-removal policy is important in reducing maternal
deaths. The Cross River State Government of Nigeria introduced a cost-removal
policy in 2009, under the umbrella of "PROJECT HOPE" where free maternal health
services are provided. Since its inception, there has been no formal evaluation
of its effectiveness. AIM: This study aims to evaluate the effect of the free
maternal health care program on the health care-seeking behaviours of pregnant
women in Cross River State, Nigeria. METHOD: A mixed method approach
(quantitative and qualitative methods) was used to describe the effect of free
maternal health care intervention. The quantitative component uses data on
maternal health service utilisation obtained from PROJECT HOPE and Nigeria
Demographic Health Survey. The qualitative part uses Focus Group Discussions to
examine women's perception of the program. RESULTS: Results suggest weak evidence
of change in maternal health care service utilization, as 95% Confidence
Intervals overlap even though point estimate suggest increase in utilization.
Results of quantitative data show increase in the percentage of women accessing
maternal health services. This increase is greater than the population growth
rate of Cross River State which is 2.9%, from 2010 to 2013. This increase is
likely to be a genuine increase in maternal health care utilisation. Qualitative
results showed that women perceived that there have been increases in the number
of women who utilize Antenatal care, delivery and Post Partum Care at health
facilities, following the removal of direct cost of maternal health services.
There is urban and rural differences as well as between communities closer to
health facility and those further off. Perceived barriers to utilization are
indirect cost of service utilization, poor information dissemination especially
in rural areas, perceived poor quality of care at facilities including drug and
consumables stock-outs, geographical barriers, inadequate health work force, and
poor attitude of skilled health workers and lack of trust in the health system.
CONCLUSION: Reasons for Maternal health care utilisation even under a cost
removal policy is multi-factorial. Therefore, in addition to fee-removal, the
government must be committed to addressing other deterrents so as to
significantly increase maternal health care service utilisation.
PMID- 28698760
TI - Impact of the Dimensions of Diversity on the Quality of Nursing Care: The Case of
Slovenia.
AB - BACKGROUND: The key to diversity in nursing is that nurses can provide competent
nursing care to patients, within the scope of their responsibilities, regardless
of the patients' personalities or primary and secondary factors. AIM: To research
which dimensions of diversity influence the attitude of nurses towards patients
and the quality of nursing care. MATERIALS AND METHODS: This research study is
based on the descriptive and causal non-experimental method of empirical
research. The independent samples t-test was used, and the within subjects ANOVA
with the Bonferroni posthoc test. RESULTS: There are statistically significant
differences among the dimensions of diversity in the arithmetic means of the
ratings of the impact on the quality of nursing (F (1.407, 579.658) = 103.307, p
< 0.001). Based on the Bonferroni test, the impact of the "personality" dimension
was rated statistically significantly higher than the impact of the dimensions of
"primary factors" (p < 0.001) and "secondary factors" (p < 0.001). CONCLUSION:
The diversity factors should be taken into account when developing knowledge of
nurses for managing patients' diversity. In modern nursing care, the safe
clinical environment needs to enable the patient to feel safe and dignified.
PMID- 28698761
TI - Vagus Nerve Stimulation.
AB - BACKGROUND: The vagus nerve stimulation (VNS) is an approach mainly used in cases
of intractable epilepsy despite all the efforts. Also, its benefits have been
shown in severe cases of depression resistant to typical treatment. AIM: The aim
of this study was to present current knowledge of vagus nerve stimulation.
MATERIAL AND METHODS: A new value has emerged just at this stage: VNS aiming the
ideal treatment with new hopes. It is based on the placement of a programmable
generator on the chest wall. Electric signals from the generator are transmitted
to the left vagus nerve through the connection cable. Control on the cerebral
bioelectrical activity can be achieved by way of these signal sent from there in
an effort for controlling the epileptic discharges. RESULTS: The rate of
satisfactory and permanent treatment in epilepsy with monotherapy is around 50%.
This rate will increase by one-quarters (25%) with polytherapy. However, there is
a patient group roughly constituting one-thirds of this population, and this
group remains unresponsive or refractory to all the therapies and combined
regimes. The more the number of drugs used, the more chaos and side effects are
observed. The anti-epileptic drugs (AEDs) used will have side effects on both the
brain and the systemic organs. Cerebral resection surgery can be required in some
patients. The most commonly encountered epilepsy type is the partial one, and the
possibility of benefiting from invasive procedures is limited in most patients of
this type. Selective amygdala-hippocampus surgery is a rising value in complex
partial seizures. Therefore, as epilepsy surgery can be performed in very limited
numbers and rather developed centres, success can also be achieved in limited
numbers of patients. The common ground for all the surgical procedures is the
target of preservation of memory, learning, speaking, temper and executive
functions as well as obtaining a good control on seizures. However, the action
mechanism of VNS is still not exactly known. On the other hand, it appears to be
a reliable method that is tolerated well in partial resistant seizures. It has
been observed that adverse effects are generally of mild-medium severity, and
most of the problems can be eliminated easily through the re-adjustment of the
stimulator. CONCLUSION: VNS, which is a treatment modality that will take place
it deserves in epilepsy treatment with "the correct patient" and "correct
reason", must be known better and its applications must be developed.
PMID- 28698762
TI - Congenital Progressive Mutilating Hemangioma.
AB - A 73-year-old male patient was admitted with symptoms of decompensated cardiac
and pulmonary insufficiency with long-lasting history. A tumor-like formation was
observed within the clinical examination, covering the whole skin of the nose,
paranasal region of the left part of the face, as well as the upper and lower
left eyelids. The lesion was with yellow to brownish surface and dark-reddish to
violet discolored peripheral area, composed of nodular formations, smooth central
surface and firm texture on palpation. The histopathological examination verified
the diagnosis of hemangioma, which had been congenital, regarding the patient's
history, treated surgically about 50 years ago, with signs of recurrence. The
presented patient had been treated surgically at the age of 20, without medical
evidence of the type of the performed excision. The recurrence occurs almost 50
years later, at the age of 78. To the best of our knowledge, this is the first
reported recurrence of infantile hemangioma, treated surgically almost 50 years
ago.
PMID- 28698763
TI - Wolf's Panniculitis.
AB - A 28-year-old male patient, presented with a one-week history of pain and itching
on the skin of the left upper leg. Erythematous indurated, warm and painful on
palpation, subcutaneous plaques and nodules were clinically observed, affecting
the skin of the left upper leg, within a recent black-wolf tattoo. The diagnosis
of traumatic panniculitis with superposed bacterial infection, provoked by a wolf
tattoo was made. The patient underwent 7-days systemic antibiotic treatment
regimen and topical application of iodine povidone unguent under occlusion for 7
days. Significant alleviation of the subjective complaints was achieved within
the first week, with a total clinical resolution of the symptoms. The role of the
procedure as a source of trauma for subcutaneous inflammation (traumatic
panniculitis) and the contamination of the equipment or the staff (infective
panniculitis) in simultaneously triggering of the pathogenetic chain of the
reported Wolf's panniculitis could be present.
PMID- 28698764
TI - Modulatory Effect of Monochromatic Blue Light on Heat Stress Response in
Commercial Broilers.
AB - In a novel approach, monochromatic blue light was used to investigate its
modulatory effect on heat stress biomarkers in two commercial broiler strains
(Ross 308 and Cobb 500). At 21 days old, birds were divided into four groups
including one group housed in white light, a second group exposed to blue light,
a 3rd group exposed to white light + heat stress, and a 4th group exposed to blue
light + heat stress. Heat treatment at 33 degrees C lasted for five h for four
successive days. Exposure to blue light during heat stress reduced MDA
concentration and enhanced SOD and CAT enzyme activities as well as modulated
their gene expression. Blue light also reduced the degenerative changes that
occurred in the liver tissue as a result of heat stress. It regulated, though
variably, liver HSP70, HSP90, HSF1, and HSF3 gene expression among Ross and Cobb
chickens. Moreover, the Cobb strain showed better performance than Ross
manifested by a significant reduction of rectal temperature in the case of H + B.
Furthermore, a significant linear relationship was found between the lowered
rectal temperature and the expression of all HSP genes. Generally, the
performance of both strains by most assessed parameters under heat stress is
improved when using blue light.
PMID- 28698765
TI - Reactive Oxygen Species-Mediated Mechanisms of Action of Targeted Cancer Therapy.
AB - Targeted cancer therapies, involving tyrosine kinase inhibitors and monoclonal
antibodies, for example, have recently led to substantial prolongation of
survival in many metastatic cancers. Compared with traditional chemotherapy and
radiotherapy, where reactive oxygen species (ROS) have been directly linked to
the mediation of cytotoxic effects and adverse events, the field of oxidative
stress regulation is still emerging in targeted cancer therapies. Here, we
provide a comprehensive review regarding the current evidence of ROS-mediated
effects of antibodies and tyrosine kinase inhibitors, use of which has been
indicated in the treatment of solid malignancies and lymphomas. It can be
concluded that there is rapidly emerging evidence of ROS-mediated effects of some
of these compounds, which is also relevant in the context of drug resistance and
how to overcome it.
PMID- 28698766
TI - Apple Flavonoids Suppress Carcinogen-Induced DNA Damage in Normal Human Bronchial
Epithelial Cells.
AB - SCOPE: Human neoplastic transformation due to DNA damage poses an increasing
global healthcare concern. Maintaining genomic integrity is crucial for avoiding
tumor initiation and progression. The present study aimed to investigate the
efficacy of an apple flavonoid fraction (AF4) against various carcinogen-induced
toxicity in normal human bronchial epithelial cells and its mechanism of DNA
damage response and repair processes. METHODS AND RESULTS: AF4-pretreated cells
were exposed to nicotine-derived nitrosamine ketones (NNK), NNK acetate (NNK-Ae),
methotrexate (MTX), and cisplatin to validate cytotoxicity, total reactive oxygen
species, intracellular antioxidants, DNA fragmentation, and DNA tail damage.
Furthermore, phosphorylated histone (gamma-H2AX) and proteins involved in DNA
damage (ATM/ATR, Chk1, Chk2, and p53) and repair (DNA-PKcs and Ku80) mechanisms
were evaluated by immunofluorescence and western blotting, respectively. The
results revealed that AF4-pretreated cells showed lower cytotoxicity, total ROS
generation, and DNA fragmentation along with consequent inhibition of DNA tail
moment. An increased level of gamma-H2AX and DNA damage proteins was observed in
carcinogen-treated cells and that was significantly (p <= 0.05) inhibited in AF4
pretreated cells, in an ATR-dependent manner. AF4 pretreatment also facilitated
the phosphorylation of DNA-PKcs and thus initiation of repair mechanisms.
CONCLUSION: Apple flavonoids can protect in vitro oxidative DNA damage and
facilitate repair mechanisms.
PMID- 28698767
TI - NRF2 Plays a Critical Role in Both Self and EGCG Protection against Diabetic
Testicular Damage.
AB - Activation of nuclear factor erythroid 2-related factor 2 (NRF2) has been found
to ameliorate diabetic testicular damage (DTD) in rodents. However, it was
unclear whether NRF2 is required for these approaches in DTD. Epigallocatechin
gallate (EGCG) is a potent activator of NRF2 and has shown beneficial effects on
multiple diabetic complications. However, the effect of EGCG has not been studied
in DTD. The present study aims to explore the role of NRF2 in both self and EGCG
protection against DTD. Therefore, streptozotocin-induced diabetic C57BL/6 wild
type (WT) and Nrf2 knockout (KO) mice were treated in the presence or absence of
EGCG, for 24 weeks. The Nrf2 KO mice exhibited more significant diabetes-induced
loss in testicular weight and spermatozoa count, and increase in testicular
apoptotic cell death, as compared with the WT mice. EGCG activated NRF2
expression and function, preserved testicular weight and spermatozoa count, and
attenuated testicular apoptotic cell death, endoplasmic reticulum stress,
inflammation, and oxidative damage in the WT diabetic mice, but not the Nrf2 KO
diabetic mice. The present study demonstrated for the first time that NRF2 plays
a critical role in both self and EGCG protection against DTD.
PMID- 28698769
TI - High-Intensity Exercise Reduces Cardiac Fibrosis and Hypertrophy but Does Not
Restore the Nitroso-Redox Imbalance in Diabetic Cardiomyopathy.
AB - Diabetic cardiomyopathy refers to the manifestations in the heart as a result of
altered glucose homeostasis, reflected as fibrosis, cellular hypertrophy,
increased oxidative stress, and apoptosis, leading to ventricular dysfunction.
Since physical exercise has been indicated as cardioprotective, we tested the
hypothesis that high-intensity exercise training could reverse the cardiac
maladaptations produced by diabetes. For this, diabetes was induced in rats by a
single dose of alloxan. Diabetic rats were randomly assigned to a sedentary group
or submitted to a program of exercise on a treadmill for 4 weeks at 80% of
maximal performance. Another group of normoglycemic rats was used as control.
Diabetic rat hearts presented cardiomyocyte hypertrophy and interstitial
fibrosis. Chronic exercise reduced both parameters but increased apoptosis.
Diabetes increased the myocardial levels of the mRNA and proteins of NADPH
oxidases NOX2 and NOX4. These altered levels were not reduced by exercise.
Diabetes also increased the level of uncoupled endothelial nitric oxide synthase
(eNOS) that was not reversed by exercise. Finally, diabetic rats showed a lower
degree of phosphorylated phospholamban and reduced levels of SERCA2 that were not
restored by high-intensity exercise. These results suggest that high-intensity
chronic exercise was able to reverse remodeling in the diabetic heart but was
unable to restore the nitroso-redox imbalance imposed by diabetes.
PMID- 28698770
TI - Analysis of Healthcare Cost and Utilization in the First Two Years of the
Medicare Shared Savings Program Using Big Data from the CMS Enclave.
AB - The Medicare Shared Savings Program (MSSP) is the larger of the first two
Accountable Care Organization (ACO) programs by the Centers for Medicare and
Medicaid Services (CMS). In this study we assessed healthcare cost and
utilization of 1.71 million Medicare beneficiaries assigned to the 333 MSSP ACOs
in the calendar years of 2013 and 2014, in comparison to years 2010 and 2011,
using the official CMS data. We employed doubly robust estimation (propensity
score weighting followed by generalized linear regression) to adjust the analyses
to beneficiary personal traits, history of chronic conditions, previous
healthcare utilization, ACO administrative region, and ZIP code socioeconomic
factors. In comparison to the care delivered to the control cohort of 17.7
million non-ACO beneficiaries, we found that the care patterns for ACO
beneficiaries shifted away from some costly types of care, but at the expense of
increased utilization of other types, increased imaging and testing expenditures,
and increased medication use, with overall net greater increase in cost instead
of smaller increase.
PMID- 28698771
TI - Finding the Hurt in Pain.
AB - Pain is unique to every person, and difficult to quantify and treat. Whether it
is delivered as a jolt or a persistent, dull ache, pain is guaranteed to affect
one's quality of life. Our author examines how brain imaging is opening our eyes
to the richness and complexity of the pain experience, giving us extraordinary
insight into the neurochemistry, network activity, wiring, and structures
relevant to producing and modulating painful experiences in all their various
guises.
PMID- 28698772
TI - Examining the Causes of Autism.
AB - Autism is a broad, complex, and increasingly important brain disorder. New data
from the Center for Disease Control and Prevention indicate that one in sixty
eight children is born with some degree of autism. Autism is also more common in
males by a four to one ratio. Making it especially difficult to discuss in
finite, conclusive terms is the fact that there is no biological test for autism;
diagnosis is based on behavior, and the only verified treatment is intensive
behavior therapy. Our author, one of the nation's foremost researchers on autism,
examines the prenatal factors that contribute to the disorder.
PMID- 28698773
TI - Next Generation House Call.
AB - Just as online shopping is supplanting visits to the mall, and distance learning
is part of the new wave in higher education, so is health care coming to a
computer or mobile device near you. In the next few years, telehealth will
increasingly become part of psychiatric and neurological care. Still to overcome
is an unwieldy health care system that will need to adapt to practices that have
the potential to lower costs and improve care.
PMID- 28698768
TI - Measurement and Clinical Significance of Biomarkers of Oxidative Stress in
Humans.
AB - Oxidative stress is the result of the imbalance between reactive oxygen species
(ROS) formation and enzymatic and nonenzymatic antioxidants. Biomarkers of
oxidative stress are relevant in the evaluation of the disease status and of the
health-enhancing effects of antioxidants. We aim to discuss the major
methodological bias of methods used for the evaluation of oxidative stress in
humans. There is a lack of consensus concerning the validation, standardization,
and reproducibility of methods for the measurement of the following: (1) ROS in
leukocytes and platelets by flow cytometry, (2) markers based on ROS-induced
modifications of lipids, DNA, and proteins, (3) enzymatic players of redox
status, and (4) total antioxidant capacity of human body fluids. It has been
suggested that the bias of each method could be overcome by using indexes of
oxidative stress that include more than one marker. However, the choice of the
markers considered in the global index should be dictated by the aim of the study
and its design, as well as by the clinical relevance in the selected subjects. In
conclusion, the clinical significance of biomarkers of oxidative stress in humans
must come from a critical analysis of the markers that should give an overall
index of redox status in particular conditions.
PMID- 28698774
TI - The Four Pillars of Alzheimer's Prevention.
AB - Much is yet to be discovered about the precise biological changes that cause
Alzheimer's, disease, why it progresses more quickly in some than in others, and
how the disease can be prevented, slowed, or stopped. And while researchers
continue to search for the magic pill that can prevent or halt the spread of
amyloid in the brain, our authors believe that changing or modifying one's
lifestyle and attitude can make a difference in both prevention and treatment.
PMID- 28698775
TI - Gut Feelings on Parkinson's and Depression.
AB - The gut-brain axis is one of the new frontiers of neuroscience. Microbiota (the
collective bacteria, viruses, fungi and other microorganisms that live in the
digestive tract), sometimes referred to as the "second genome" or the "second
brain," may influence our health in ways that scientists are just now beginning
to understand. Scientists now believe that the microbiota and all that it
involves may be a way to treat any number of disorders, including Parkinson's
disease and depression.
PMID- 28698776
TI - The Sleeping Brain.
AB - The role of sleep has long baffled scientists, but the latest research is
providing new indicators about what it does for both the brain and body. While
scientists believe that sleep re-energizes the body's cells, clears waste from
the brain, and supports learning and memory, much still needs to be learned about
the part it plays in regulating mood, appetite and libido. Source/Shutterstock.
PMID- 28698777
TI - Genetics and ALS: Cause for Optimism.
AB - While drug development has done little to slow the devastating symptoms of
amyotrophic lateral sclerosis (ALS), there is some good news in the fact that
scientists have identified some 100 related genes and believe that genetic
research offers the best hope for treatments. More good news came on the heels of
the Ice Bucket Challenge, which raised $220 million globally and has fueled
renewed optimism and energy in the ALS community.
PMID- 28698778
TI - Eric Kandel's Reductionism in Art and Brain Science - Bridging the Two Cultures.
AB - Reductive art is a term to describe an artistic style or an aesthetic, rather
than an art movement. It is stripping down as a new way of seeing. Movements and
other terms that are sometimes associated with reductive art include abstract
art, minimalism, ABC art, anti-illusionism, cool art, and rejective art. Eric
Kandel's fifth book focuses on reductionism as the principle guiding an ongoing
dialogue between the worlds of science and art.
PMID- 28698779
TI - Bacterial Blood Stream Infections Negatively Impact on Outcome of Patients
Treated with Allogeneic Stem Cell Transplantation: 6 Years Single-Centre
Experience.
AB - BACKGROUND: Blood stream infections (BSIs) represent a major complication of allo
SCT and are a major cause of morbidity and mortality during and after bone marrow
aplasia. OBJECTIVES: The objective of this study was to describe the incidence
and outcome of BSIs in a cohort of patients submitted to allo-SCT, in order to
track changes of the epidemiology and bacteria resistance. METHODS: We
retrospectively analyzed the microbiological data of 162 patients
allotransplanted in Brescia University Hospital, over a period of 6 years.
RESULTS: Eighty patients experienced a BSIs for a total of 119 isolates. In 77
cases (65%) a Gram positive bacteria was isolated, being coagulase negative
Staphilococci the most frequent species (77% of the cases). In 42 cases (35%) a
Gram negative bacteria was isolated (E. coli 57% and P. aeruginosa 24%).
Fluoroquinolones resistance was frequent (90% for S. epidermidis, 92% for E.
coli, 90% for P. aeruginosa). Methycillin resistance of S. epidermidis was 100%,
76% of E. coli were ESBL positive and among P. aeruginosa resistance to
carbapenems was 40%. The 2 years overall survival of patients with BSIs vs
patients without BSIs was 46% vs 60% (HR1,48, p=0,07). P. aeruginosa and E. coli
were the species with the highest mortality (50% and 33%, respectively).
CONCLUSIONS: These data confirm that BSIs, mainly sustained by Gram positive
bacteria, are frequent in allotransplanted patients (50% of the cases) and may
influence the outcome of allotransplanted patients, being antibiotics resistance
highly frequent among these bacteria.
PMID- 28698780
TI - Liver Iron Content (LIC) in Adults with Sickle Cell Disease (SCD): Correlation
with Serum Ferritin and Liver Enzymes Concentrations in Trasfusion Dependent (TD
SCD) and Non-Transfusion Dependent (NT-SCD) Patients.
AB - INTRODUCTION: Sickle cell disease (SCD) is one of the leading causes of morbidity
and mortality worldwide, causing damage and dysfunction in multiple organs. The
complications of this disease are numerous, affect every organ and/or tissue in
the body and vary considerably among patients over the time challenging its
management. THE AIM OF OUR STUDY: To determine the iron status of 17 patients
with non-transfusion-dependent sickle cell disease ( NT-SCD) patients and six
patients with transfusion dependent sickle cell disease (TD- SCD) using both
serum ferritin level (SF) and Ferriscan(r) evaluation of liver iron content
(LIC). We correlated the values of LIC with SF levels and some hepatic enzymes
(alanine transaminase-ALT, aspartate aminotransferase -AST, alkaline phosphatase
ALP and albumin). RESULTS: 17 adults with NT-SCD (n = 17, age: 32+/-15 years)
were studied. Seven of NT-SCD had SF > 500 MUg/L, 4 out of the seven had high
liver iron measured by FerriScan(r) (> 30 mg/g/ tissue dry weight - dw). Two
patients had high LIC despite a concomitant SF concentration < 500 MUg/L. Two
patients had high SF (1.117 MUg/L and 675 MUg/L) while their LIC was normal (< 30
mg/g/dw). Five patients had elevated ALT and/or AST) concentrations. In TD-SCD (n
= 6, age = 25 +/- 11 years), 2 patients had SF <500 MUg/L, one of them had high
LIC (127 mg/g/DW). Liver enzymes were high in two patients. SF concentration
correlated significantly with LIC (r = 0.85, p < 0.001). Neither SF level nor LIC
was correlated significantly with hepatic enzyme levels. CONCLUSIONS: A
significant number of our patients with NT-SCD had high LIC, high SF and elevated
liver enzymes (ALT and AST). Despite some limitations of our study, due to the
limited number of NT-SCD patients, these findings have important clinical
implications. Therefore, we recommend measuring SF and LIC in NT-SCD patients to
apply preventive measures with iron chelation therapy in patients with high LIC.
PMID- 28698781
TI - Idiopathic Pulmonary Embolism in a case of Severe Family ANKRD26
Thrombocytopenia.
AB - Venous thrombosis affecting thrombocytopenic patients is challenging. We report
the case of a woman affected by deep vein thrombosis and pulmonary embolism in a
thrombocytopenic context leading to the discovery of a heterozygous mutation in
the gene encoding ankyrin repeat domain 26 (ANKRD26) associated with a
heterozygous factor V (FV) Leiden mutation. This woman was diagnosed with lower
limb deep vein thrombosis complicated by pulmonary embolism. Severe
thrombocytopenia was observed. The genetic study evidenced a heterozygous FV
Leiden mutation. Molecular study sequencing was performed after learning that her
family had a history of thrombocytopenia. Previously described heterozygous
mutation c-127C>A in the 5'untranslated region (5'UTR) of the ANKRD26 gene was
detected in the patient, her aunt, and her grandmother. ANKRD26-related
thrombocytopenia and thrombosis are rare. This is, to our knowledge, the first
case reported in the medical literature. This mutation should be screened in
patients with a family history of thrombocytopenia.
PMID- 28698782
TI - Prevalence and Etiology of Bacteremia in Febrile Children with Sickle Cell
Disease at a Nigeria Tertiary Hospital.
AB - BACKGROUND & OBJECTIVES: As a result of immune defects in Sickle cell disease
(SCD), affected individuals are prone to infection from encapsulated bacterial
pathogens like Streptococcus Pneumoniae. Studies on the etiological agents of
bacteremia in children with SCD in Nigeria are few and have revealed a spectrum
of organisms that is different from those recorded in other parts of the world.
AIM AND OBJECTIVES: The objectives of this study were to determine the prevalence
of bacteremia, etiological agents and antibiotic susceptibility pattern in
febrile children with SCD attending the University College Hospital (UCH),
Ibadan, Nigeria. METHODS: The study was cross-sectional and took place at the
Department of Pediatrics of the UCH, Ibadan. Children with SCD, ages 0-17 years
presenting with axillary temperature >= 38 degrees C were enrolled after
obtaining informed consent. History was obtained and complete physical
examination performed after which blood was collected for culture and
antibacterial susceptibility tests. RESULTS: A total of 116 children were studied
of which 69 (59.5%) were males, 111 (95.7%) were of the Hemoglobin SS phenotype
and 5 (4.3%) of the Hemoglobin SC phenotype. Bacteremia was present in 16 (13.8%)
of the 116 children. Gram negative bacteria constituted 10 (62.5%) of all
isolates, while the predominant isolates were Klebsiella pneumoniae 4, (25%) and
Staphylococcus aureus, 4 (25%). Over 80% of the isolates were susceptible to
Ceftriaxone, Amikacin and Meropenem. CONCLUSIONS: Klebsiella pneumoniae and
Staphylococcus aureus are the predominant causes of bacteremia in children with
SCD in Ibadan, contrary to findings in western countries.
PMID- 28698783
TI - Lenalidomide and Temozolomide Combination in a Very Elderly Patient with CNS
Relapse of Diffuse Large B-Cell Lymphoma.
AB - Central nervous system (CNS) relapse is an infrequent but severe complication for
DLBCL patients, associated with poor prognosis. Intravenous prophylaxis with high
dose methotrexate has shown promising results but is rarely feasible in elderly
and/or nephropathic patients. A 83 years old woman with CNS relapse occurred 6
months after chemoimmunotherapy. The patient was defined ineligible for
radiotherapy (RT) and started oral Temozolomide 250mg daily for 5 consecutive
days without any improvement after 1st cycle. We administered lenalidomide 25mg
daily for 21 days every 28 days together with temozolomide 250mg daily for 5 days
every 28 days. The patient experienced a rapid improvement of general and
cognitive conditions; Gadolinium-enhanced brain MRI showed a wide reduction of
neoplastic tissue. The patients maintained good clinical conditions with mild
treatment toxicity until the end of the 6th cycle, when brain MRI showed disease
progression and the patient died 1 month later. We suggest lenalidomide could be
a feasible option for CNS relapse in elderly DLBCL patients and it could be
associated in future studies with other cytotoxic agents such as temozolomide.
PMID- 28698784
TI - Albumin Cobalt Binding or Ischaemia Modified Albumin: a Test of Great Prognostic
Value in Malaria.
AB - BACKGROUND: We evaluated albumin cobalt binding (ACB) assay also known as
Ischaemia Modified Albumin (IMA) assay as a prognostic marker for severe malaria
in a medical college setting. METHODS: Consecutive adult patients admitted with
both vivax and falciparum malaria were evaluated with ACB assay at the time of
admission. Detailed work up and individual patient directed management were
instituted in addition to immediate artemisin based antimalarial therapy.
RESULTS: 100 consecutive patients (50 with vivax and 50 with falciparum malaria)
were evaluated. The reference range for ACB assay was established using 50 adult
healthy (25 male and 25 female) individuals. 16 out of 50 p. Falciparum-Infected
developed complicated malaria. None of the P Vivax patients developed complicated
malaria. All malaria infected patients had high ACB levels (P<0.0001). There was
a stepwise increase in ACB levels from healthy volunteers to different categories
of malaria (P<0.0001) without any overlap. CONCLUSION: ACB has the potential to
be used as a robust simple and inexpensive prognostic marker for organ
dysfunction in severe malaria even if an evaluation at multiple sites with a
bigger number of patients should be initiated for final recommendation.
PMID- 28698785
TI - Haptoglobin Phenotypes and Susceptibility to Schistosoma Parasites Infection in
Central Sudan.
AB - Haptoglobin (Hp) is an acute phase protein that binds the free hemoglobin (Hb),
thus preventing iron loss and renal damage. Hp also has antioxidative and
immunomodulatory properties. Three Hp phenotypes have been identified in human:
Hp1-1, Hp2-1, and Hp2-2. Hp polymorphisms have been related to susceptibility of
various diseases. In this study, we aimed to assess the possible association of
Hp phenotypes polymorphism to Schistosoma parasites infection in central Sudan.
We have investigated the Hp phenotypes polymorphism distribution in the serum of
125 (93 S. mansoni, 13 S. haematobium and 19 infected with both "co-infection")
parasitologically confirmed infected individuals and 208 healthy individuals
served as control. Hp phenotypes have been determined by polyacrylamide gel
electrophoresis followed by benzidine staining. Our study revealed that Hp1-1
percentage frequency was significantly higher in infected individuals than
healthy control individuals 51% and 26% respectively. Our data suggest that Hp1-1
phenotype may upsurge the susceptibility to Schistosoma parasites infection in
central Sudan.
PMID- 28698786
TI - Emerging Cases of Pertussis Among Early Infants Born to Unvaccinated Mothers, an
Infectious Disease Long Absent in Northwestern Greece.
PMID- 28698787
TI - Peripheral T-Cell Lymphoma in Mediastinum Lymph Nodes and Lung Associated to
Histoplasmosis in a Patient with Chronic Lymphoid Leukemia/Small Lymphocytic
Lymphoma.
PMID- 28698788
TI - Treatment of Low-Blast Count AML using Hypomethylating Agents.
AB - In 2002, the WHO classification reduced the proportion of blasts in the bone
marrow (BM) necessary for the diagnosis of acute myeloid leukemia (AML) from 30%
to 20%, eliminating the RAEB-t subtype of myelodysplastic syndromes (MDS).
However, this AML subtype, defined as low-blast count AML (LBC-AML, with 20-30%
BM-blasts) is characterized by peculiar features, as increased frequency in
elderly individuals and after cytotoxic treatment for a different primary disease
(therapy-related), poor-risk cytogenetics, lower white blood cell counts, and
less frequent mutations of NPM1 and FLT3 genes. The clinical course of this
entity is often similar to MDS with 10-19% BM-blasts. The hypomethylating agents
azacitidine and decitabine have been shown to induce responses and prolong
survival both in MDS and LBC-AML. The role of these agents has also been
demonstrated in AML with >30% BM-blasts, particularly in patients with poor-risk
cytogenetics and in AML with myelodysplasia-related changes. Most recent studies
are evaluating strategies to improve outcome, including combinations of
hypomethylating agents with immune-response checkpoint inhibitors, which have a
role in cancer immune surveillance. Efforts are also ongoing to identify
mutations which may predict response and survival in these patients.
PMID- 28698789
TI - A Population-Based Study on Myelodysplastic Syndromes in the Lazio Region
(Italy), Medical Miscoding and 11-Year Mortality Follow-Up: the Gruppo Romano
Laziale Mielodisplasie Experience of Retrospective Multicentric Registry.
AB - Data on Myelodysplastic Syndromes (MDS) are difficult to collect by cancer
registries because of the lack of reporting and the use of different
classifications of the disease. In the Lazio Region, data from patients with a
confirmed diagnosis of MDS, treated by a hematology center, have been collected
since 2002 by the Gruppo Romano-Laziale Mielodisplasie (GROM-L) registry, the
second MDS registry existing in Italy. This study aimed at evaluating MDS medical
miscoding during hospitalizations, and patients' survival. For these purposes, we
selected 644 MDS patients enrolled in the GROM-L registry. This cohort was linked
with two regional health information systems: the Hospital Information System
(HIS) and the Mortality Information System (MIS) in the 2002-2012 period. Of the
442 patients who were hospitalized at least once during the study period, 92% had
up to 12 hospitalizations. 28.5% of patients had no hospitalization episodes
scored like MDS, code 238.7 of the International Classification of Disease, Ninth
Revision, Clinical Modification (ICD-9-CM). The rate of death during a median
follow-up of 46 months (range 0.9-130) was 45.5%. Acute myeloid leukemia (AML)
was the first cause of mortality, interestingly a relevant portion of deaths is
due to cerebro-cardiovascular events and second tumors. This study highlights
that MDS diagnosis and treatment, which require considerable healthcare
resources, tend to be under-documented in the HIS archive. Thus we need to
improve the HIS to better identify information on MDS hospitalizations and
outcome. Moreover, we underline the importance of comorbidity in MDS patients'
survival.
PMID- 28698790
TI - Sequential stamen maturation and movement in a protandrous herb: mechanisms
increasing pollination efficiency and reducing sexual interference.
AB - Successive stamen movement directly controls pollen presentation schedules
through sequential stamen maturation and changes the extent of herkogamy by
altering the positions of sexual organs. However, the implications of such
movements in terms of pollination are not well understood. Pollen presentation
theory predicts that staggered pollen presentation should be favoured when plants
are subject to diminishing returns on pollen transfer. Herkogamy on the other
hand, has been interpreted as an adaptive trait that reduces sexual interference
in hermaphrodite flowers. In this study, we conducted floral manipulations to
determine the function of successive stamen movement in pollen transfer. By
artificially manipulating the flowers to present two anthers simultaneously in
the floral centre, we attempted to investigate whether changes in the anther
presentation strategy affect pollen removal, deposition and the efficiency of
pollinators. Compared with the natural treatment, the pollen transfer efficiency
of halictid bees decreased significantly when the flowers were manipulated to
present two anthers simultaneously. Although the presentation of two anthers
simultaneously led to a similar pollen removal rate, there was a significant
reduction in pollen deposition on neighbouring stigmas. To evaluate the effect of
movement herkogamy on pollen export and deposition and seed set, the flowers were
manipulated with or without the movement of stamen bending out from the floral
centre. Pollen export decreased significantly when the central anther was moved
away from the pistil, and pollen deposition and seed set declined significantly
when the five spent anthers were retained on the pistil. Our study provides good
support for the pollen presentation theory and provides direct experimental
evidence that successive stamen movement could increase pollen transfer
efficiency by sequential stamen maturation. Moreover, movement herkogamy promotes
pollen export, deposition and seed set, and could therefore be regarded as an
effective mechanism to reduce interference between male and female functions.
PMID- 28698791
TI - First reported case of paratesticular seminoma in a postpubertal cryptorchid
testis.
AB - Cryptorchidism is a very common anomaly, affecting 2-4% of male infants and is
more common in premature infants. The long-term outcome despite orchidopexy still
remains problematic and controversial with a risk of developing cancer 5-10 times
greater than normal. Paratesticular tumors are mostly benign and very rare in
children however malignant paratesticular tumors do arise, the most common being
rhabdomyosarcoma. Primary paratesticular seminoma is extremely rare by itself and
in most cases is associated with foci of seminoma within the testis. To the best
of our knowledge, our case represents the fourth reported case of paratesticular
seminoma in the published literature and being the first one in cryptorchid
testis.
PMID- 28698792
TI - Complete cricotracheal transection due to blunt neck trauma without significant
symptoms.
AB - Laryngotracheal injuries are relatively rare but their mortality rate is fairly
high. Complete disruption of trachea is extremely rare and a systematic approach
is needed for early diagnosis and favourable outcome. The patients symptoms and
physical signs do not necessarily correlate with the severity of the injuries and
this case report highlights it. This is a case report of 25-year-old man who
arrived to the emergency department 8 h after a motor accident in which a rope
was wrapped around his neck. Because of the good general and respiratory
condition of the patient on admission, the pathognomonic signs of laryngeal
injury were not noticed. A computed tomographic scan showed distortion of
cricotracheal framework. Flexible bronchoscopy showed cricotracheal transaction.
Immediately, the endotracheal tube was advanced distal to the transection site
under bronchoscopic guide and then after neck exploration primary end-to-end
cricotracheal anastomosis was performed.
PMID- 28698793
TI - Wide rectal duplication cyst in an adult resected by anterior approach: efficacy
and recurrence.
AB - Alimentary tract duplications are uncommon congenital abnormalities usually
diagnosed and treated in childhood. Rectal involvement is extremely rare. We
report the case of a 22-year-old female who presented with chronic abdominal and
perianal pain; feeling of rectal fullness. Workup revealed a rectal duplication
cyst. The patient underwent a complete transabdominal excision of the cyst: an
hybrid laparoscopic and laparotomic technique was adopted. The hybrid isolated
anterior abdominal approach is safe and feasible even for the treatment of wide
rectal duplication cysts. Real recurrence in rectal duplication cysts is uncommon
when the first operation was performed with radical intent.
PMID- 28698794
TI - Robotic right segmental hepatectomy for the treatment of a giant hepatic
hemangioma-a case report.
AB - Hemangioma is the most common benign hepatic tumor. We present the case of a
patient with a giant symptomatic hemangioma, treated with segmental liver
resection using the Da Vinci Robotic System. A 38-year-old woman presented to our
surgical out-patient Department complaining about abdominal discomfort and
recurrent episodes of acute abdominal pain. CT-scan and MRI imaging of the
abdomen revealed the presence of a giant hepatic hemangioma (>5 cm) involving
segments VI and VII. Robotic right segmental hepatectomy was performed. The
procedure was successfully completed in 120 min and with intraoperative blood
loss of only 450 ml. Postoperative period was uneventful and the patient was
discharged on the second postoperative day. In case of giant hemangiomas, a
minimally invasive robotic major hepatic resection is a viable option that can be
performed with minimal complications. A careful preoperative and intraoperative
strategy is required, while significant experience in liver and robotic surgery
is mandatory.
PMID- 28698795
TI - Semi-automated Modular Program Constructor for physiological modeling: Building
cell and organ models.
AB - The Modular Program Constructor (MPC) is an open-source Java based utility, built
upon JSim's Mathematical Modeling Language (MML) ( http://www.physiome.org/jsim/)
that uses directives embedded in model code to construct larger, more complicated
models quickly and with less error than manually combining models. A major
obstacle in writing complex programs for modeling physiological processes is the
large amount of time it takes to code the myriad processes taking place
simultaneously in cells, tissues, and organs. MPC replaces this task by code
generating algorithms that take the code from several different modules and
produce model code for a new JSim model. This is particularly useful during multi
scale model development where many variants are to be configured and tested
against data. MPC is implemented in Java and requires JSim to use its output. MPC
source code and documentation are available at
http://www.physiome.org/software/MPC/.
PMID- 28698796
TI - Forest disturbance leaves some bats stressed and under the weather.
PMID- 28698798
TI - Patients expectations and fulfilment of expectations before and after treatment
for suspected coronary artery disease assessed with a newly developed
questionnaire in combination with established health-related quality of life
questionnaires.
AB - BACKGROUND: Clinical decision-making is often based on evidence of outcome after
a specific treatment. Healthcare providers and patients may, however, have
different perceptions and expectations of what to achieve from a certain
healthcare measure. AIMS: To evaluate patients' expectations, perceptions and
health related quality of life (HRQoL) before a care process including coronary
angiography for suspected coronary artery disease and to evaluate the fulfilment
of these expectations in relation to established patient reported outcome
measures (PROMs) 6 months later. Furthermore, an aim was to try to define
meaningful patient reported experience measures (PREMs) in this population.
METHODS: 544 patients planned for coronary angiography completed a newly
developed questionnaire to assess expectations and perceptions of treatment, the
expectation questionnaire (ExpQ) and two established HRQoL questionnaires
together with the established generic Short-Form 36 (SF36) and the disease
specific Seattle Angina Questionnaire (SAQ). RESULTS: Patients had before the
intervention, in general, high expectations of improvement after investigation
and treatment and there was a positive attitude towards life style changes,
medication and participation in decision-making regarding their own treatment.
Only, 56.4% of the patients, however, reported fulfilment of treatment
expectations. Fulfilment of treatment expectations correlated strongly with
improvement in HRQoL after the care process. CONCLUSIONS: To measure patients '
expectations and fulfilments of these may offer simple and meaningful outcomes to
evaluate a healthcare process from a patient 's perspective. To approach
patients' expectations may also strengthen patient involvement in the care
process with the possibilities of both higher patient satisfaction and medical
results of the treatment.
PMID- 28698797
TI - New technologies accelerate the exploration of non-coding RNAs in horticultural
plants.
AB - Non-coding RNAs (ncRNAs), that is, RNAs not translated into proteins, are crucial
regulators of a variety of biological processes in plants. While protein-encoding
genes have been relatively well-annotated in sequenced genomes, accounting for a
small portion of the genome space in plants, the universe of plant ncRNAs is
rapidly expanding. Recent advances in experimental and computational technologies
have generated a great momentum for discovery and functional characterization of
ncRNAs. Here we summarize the classification and known biological functions of
plant ncRNAs, review the application of next-generation sequencing (NGS)
technology and ribosome profiling technology to ncRNA discovery in horticultural
plants and discuss the application of new technologies, especially the new genome
editing tool clustered regularly interspaced short palindromic repeat
(CRISPR)/CRISPR-associated protein 9 (Cas9) systems, to functional
characterization of plant ncRNAs.
PMID- 28698799
TI - Adults with repaired tetralogy: low mortality but high morbidity up to middle
age.
AB - OBJECTIVE: Survival of patients with repaired tetralogy of Fallot (rToF) into
young adulthood is very good. Concerns exist, however, over long-term morbidity
and mortality as these subjects reach middle age. We aimed to assess survival and
the prevalence of complications in patients with rToF seen in our Adult
Congenital Heart Disease (ACHD) service. METHODS: One hundred and sixty-eight
consecutive patients with 'simple rToF', aged over 16 years, followed up at our
tertiary-level ACHD service in Sydney, Australia since 2000, were included. We
documented mortality and analysed the prospectively defined composite end points
of (a) 'Serious adverse events', including death, heart failure hospitalisation
and/or documented ventricular arrhythmia and (b) 'Adverse events' inclusive of
the above and endocarditis, atrial arrhythmia, defibrillator and/or pacemaker
implantation. RESULTS: Mean age at the last follow-up was 34+/-12 years, and 55%
were men. There were 10 (6%) deaths, and 26 patients (16%) experienced a 'serious
adverse event'. Fifty-one patients (30%) experienced an 'adverse event' and 29
patients had atrial arrhythmias. One hundred and one (61%) patients had at least
one pulmonary valve replacement. By age 40 years, 93% were free of serious
adverse events, and 83% were free of any adverse event. By age 50 years, only 56%
had not had an adverse event. Older age and history of atrial arrhythmia were
predictive of serious adverse events. CONCLUSION: Survival into mid-adulthood in
patients with rToF is very good; however, a substantial number of survivors have
adverse events by the age of 50 years.
PMID- 28698800
TI - Metformin-induced ablation of microRNA 21-5p releases Sestrin-1 and CAB39L
antitumoral activities.
AB - Metformin is a commonly prescribed type II diabetes medication that exhibits
promising anticancer effects. Recently, these effects were found to be
associated, at least in part, with a modulation of microRNA expression. However,
the mechanisms by which single modulated microRNAs mediate the anticancer effects
of metformin are not entirely clear and knowledge of such a process could be
vital to maximize the potential therapeutic benefits of this safe and well
tolerated therapy. Our analysis here revealed that the expression of miR-21-5p
was downregulated in multiple breast cancer cell lines treated with
pharmacologically relevant doses of metformin. Interestingly, the inhibition of
miR-21-5p following metformin treatment was also observed in mouse breast cancer
xenografts and in sera from 96 breast cancer patients. This modulation occurred
at the levels of both pri-miR-21 and pre-miR-21, suggesting transcriptional
modulation. Antagomir-mediated ablation of miR-21-5p phenocopied the effects of
metformin on both the clonogenicity and migration of the treated cells, while
ectopic expression of miR-21-5p had the opposite effect. Mechanistically, this
reduction in miR-21-5p enhanced the expression of critical upstream activators of
the AMP-activated protein kinase, calcium-binding protein 39-like and Sestrin-1,
leading to AMP-activated protein kinase activation and inhibition of mammalian
target of rapamycin signaling. Importantly, these effects of metformin were
synergistic with those of everolimus, a clinically relevant mammalian target of
rapamycin inhibitor, and were independent of the phosphatase and tensin homolog
status. This highlights the potential relevance of metformin in combinatorial
settings for the treatment of breast cancer.
PMID- 28698801
TI - TAK1 inhibition attenuates both inflammation and fibrosis in experimental
pneumoconiosis.
AB - Pneumoconiosis, caused by inhalation of mineral dusts, is a major occupational
disease worldwide. Currently, there are no effective drugs owing to a lack of
potential therapeutic targets during either the inflammation or fibrosis
molecular events in pneumoconiosis. Here, we performed microarrays to identify
aberrantly expressed genes in the above molecular events in vitro and found a hub
gene transforming growth factor-beta-activated kinase 1 (TAK1), which was highly
expressed and activated in pneumoconiosis patients as well as silica-exposed rats
with experimental pneumoconiosis. Genetic modulation of TAK1 by CRISPR (clustered
regularly interspaced short palindromic repeats)/Cas9, RNA interference and
overexpression indicated the important role of TAK1 in both inflammation and
fibrosis in experimental pneumoconiosis. To achieve pharmacological TAK1
inhibition, we virtually screened out a natural product resveratrol, which
targeted TAK1 at both N161 and A107 residues, and significantly inhibited TAK1
activation to attenuate inflammation and fibrosis in vitro. Consistently, in vivo
prevention and intervention studies showed that resveratrol could inhibit
pulmonary inflammation and fibrosis in silica-exposed rats.
PMID- 28698802
TI - Gait analysis in children with cerebral palsy.
AB - Cerebral palsy (CP) children present complex and heterogeneous motor disorders
that cause gait deviations.Clinical gait analysis (CGA) is needed to identify,
understand and support the management of gait deviations in CP. CGA assesses a
large amount of quantitative data concerning patients' gait characteristics, such
as video, kinematics, kinetics, electromyography and plantar pressure data.Common
gait deviations in CP can be grouped into the gait patterns of spastic hemiplegia
(drop foot, equinus with different knee positions) and spastic diplegia (true
equinus, jump, apparent equinus and crouch) to facilitate communication. However,
gait deviations in CP tend to be a continuum of deviations rather than well
delineated groups. To interpret CGA, it is necessary to link gait deviations to
clinical impairments and to distinguish primary gait deviations from compensatory
strategies.CGA does not tell us how to treat a CP patient, but can provide
objective identification of gait deviations and further the understanding of gait
deviations. Numerous treatment options are available to manage gait deviations in
CP. Generally, treatments strive to limit secondary deformations, re-establish
the lever arm function and preserve muscle strength.Additional roles of CGA are
to better understand the effects of treatments on gait deviations. Cite this
article: Armand S, Decoulon G, Bonnefoy-Mazure A. Gait analysis in children with
cerebral palsy. EFORT Open Rev 2016;1:448-460. DOI: 10.1302/2058-5241.1.000052.
PMID- 28698803
TI - Sports activities after total hip arthroplasty.
AB - Performing sports after total hip arthroplasty (THA) may be associated with a
risk of Trauma (fracture and dislocation)Shorter implant survivalThere is no
proof that trauma occurs more often than in healthy individuals, but sequelae may
be more severe.Shorter implant survival due to repetitive high contact forces is
a fact, due to increased wear. The 15 year survival in highly active patients
seems to be around 80%.Surgeons can address the needs of active patients by using
bearings with low wear rates, and femoral heads up to 36 mm in diameter.The data
provided in this review may help to fully inform active patients of the risks.
The patient has to balance the pros and cons of sports after THA and to decide
the best way for themselves. Cite this article: EFORT Open Rev 2017;2. DOI:
10.1302/2058-5241.2.160059. Originally published online at
www.efortopenreviews.org.
PMID- 28698804
TI - The knee meniscus: management of traumatic tears and degenerative lesions.
AB - Meniscectomy is one of the most popular orthopaedic procedures, but long-term
results are not entirely satisfactory and the concept of meniscal preservation
has therefore progressed over the years. However, the meniscectomy rate remains
too high even though robust scientific publications indicate the value of
meniscal repair or non-removal in traumatic tears and non-operative treatment
rather than meniscectomy in degenerative meniscal lesionsIn traumatic tears, the
first-line choice is repair or non-removal. Longitudinal vertical tears are a
proper indication for repair, especially in the red-white or red-red zones.
Success rate is high and cartilage preservation has been proven. Non-removal can
be discussed for stable asymptomatic lateral meniscal tears in conjunction with
anterior cruciate ligament (ACL) reconstruction. Extended indications are now
recommended for some specific conditions: horizontal cleavage tears in young
athletes, hidden posterior capsulo-meniscal tears in ACL injuries, radial tears
and root tears.Degenerative meniscal lesions are very common findings which can
be considered as an early stage of osteoarthritis in middle-aged patients. Recent
randomised studies found that arthroscopic partial meniscectomy (APM) has no
superiority over non-operative treatment. Thus, non-operative treatment should be
the first-line choice and APM should be considered in case of failure: three
months has been accepted as a threshold in the ESSKA Meniscus Consensus Project
presented in 2016. Earlier indications may be proposed in cases with considerable
mechanical symptoms.The main message remains: save the meniscus! Cite this
article: EFORT Open Rev 2017;2. DOI: 10.1302/2058-5241.2.160056. Originally
published online at www.efortopenreviews.org.
PMID- 28698805
TI - MicroRNA-26a inhibits the growth and invasiveness of malignant melanoma and
directly targets on MITF gene.
AB - Metastatic melanoma is the most aggressive form of skin cancer and is refractory
to therapy. MicroRNAs have been recently discovered as novel molecules that
provide therapeutic benefits against melanoma. This work aims to examine the
effects of miR-26a and let-7a on the growth and invasiveness of malignant
melanoma in vitro and in vivo. In addition, we elucidate the mechanism of action
by identifying the target gene of miR-26a. Both miR-26a and let-7a inhibited
proliferation and invasiveness and halted the cell cycle at the G1/G0 phase in
SKMEL-28 and WM1552C malignant melanoma cell lines. Moreover, miR-26a potently
induced apoptosis and downregulated the expressions of microphthalmia-associated
transcription factor (MITF) and MAP4K3 in both cell lines. The luciferase
reporter assay demonstrated that miR-26a suppresses MITF expression by binding
the 3'-UTR, suggesting that MITF is a bona fide target of miR-26a. SiRNA
knockdown of the MITF gene confirmed that miR-26a reduced cell viability and
induced apoptosis by regulating MITF. Using a murine model, we also found miR-26a
significantly retarded the growth of melanoma tumors in vivo. In conclusion, miR
26a and let-7a suppressed the growth and invasiveness of melanoma cells,
suggesting that miR-26a and let-7a may represent novel therapies for malignant
melanoma.
PMID- 28698806
TI - Epigallocatechin-3-gallate enhances ER stress-induced cancer cell apoptosis by
directly targeting PARP16 activity.
AB - Poly(ADP-ribose) polymerases (PARPs) are ADP-ribosylating enzymes and play
important roles in a variety of cellular processes. Most small-molecule PARP
inhibitors developed to date have been against PARP1, a poly-ADP-ribose
transferase, and suffer from poor selectivity. PARP16, a mono-ADP-ribose
transferase, has recently emerged as a potential therapeutic target, but its
inhibitor development has trailed behind. Here we newly characterized
epigallocatechin-3-gallate (EGCG) as a potential inhibitor of PARP16. We found
that EGCG was associated with PARP16 and dramatically inhibited its activity in
vitro. Moreover, EGCG suppressed the ER stress-induced phosphorylation of PERK
and the transcription of unfolded protein response-related genes, leading to
dramatically increase of cancer cells apoptosis under ER stress conditions, which
was dependent on PARP16. These findings newly characterized EGCG as a potential
inhibitor of PARP16, which can enhance the ER stress-induced cancer cell
apoptosis, suggesting that a combination of EGCG and ER stress-induced agents
might represent a novel approach for cancer therapy or chemoprevention.
PMID- 28698807
TI - The 2D Structure of the T. brucei Preedited RPS12 mRNA Is Not Affected by
Macromolecular Crowding.
AB - Mitochondrial transcript maturation in African trypanosomes requires RNA editing
to convert sequence-deficient pre-mRNAs into translatable mRNAs. The different
pre-mRNAs have been shown to adopt highly stable 2D folds; however, it is not
known whether these structures resemble the in vivo folds given the extreme
"crowding" conditions within the mitochondrion. Here, we analyze the effects of
macromolecular crowding on the structure of the mitochondrial RPS12 pre-mRNA. We
use high molecular mass polyethylene glycol as a macromolecular cosolute and
monitor the structure of the RNA globally and with nucleotide resolution. We
demonstrate that crowding has no impact on the 2D fold and we conclude that the
MFE structure in dilute solvent conditions represents a good proxy for the
folding of the pre-mRNA in its mitochondrial solvent context.
PMID- 28698808
TI - Vitamins K1 and K2: The Emerging Group of Vitamins Required for Human Health.
AB - OBJECTIVE: To review the evidence for the use of vitamin K supplementation in
clinical conditions such as osteoporosis, vascular calcification, arthritis,
cancer, renal calculi, diabetes, and warfarin therapy. QUALITY OF EVIDENCE:
PubMed was searched for articles on vitamin K (K1 and K2) along with books and
conference proceedings and health conditions listed above. Level I and II
evidence supports the use of vitamins K1 and K2 in osteoporosis and Level II
evidence supports vitamin K2 in prevention of coronary calcification and
cardiovascular disease. Evidence is insufficient for use in diabetes, arthritis,
renal calculi, and cancer. MAIN MESSAGE: Vitamin K2 may be a useful adjunct for
the treatment of osteoporosis, along with vitamin D and calcium, rivaling
bisphosphonate therapy without toxicity. It may also significantly reduce
morbidity and mortality in cardiovascular health by reducing vascular
calcification. Vitamin K2 appears promising in the areas of diabetes, cancer, and
osteoarthritis. Vitamin K use in warfarin therapy is safe and may improve INR
control, although a dosage adjustment is required. CONCLUSION: Vitamin K
supplementation may be useful for a number of chronic conditions that are
afflicting North Americans as the population ages. Supplementation may be
required for bone and cardiovascular health.
PMID- 28698809
TI - P-Rex1 Expression in Invasive Breast Cancer in relation to Receptor Status and
Distant Metastatic Site.
AB - BACKGROUND: Phosphatidylinositol-3,4,5-trisphosphate-dependent Rac exchange
factor 1 (P-Rex1) has been implicated in cancer growth, metastasis, and response
to phosphatidylinositol 3-kinase (PI3K) inhibitor therapy. The aim of this study
was to determine whether P-Rex1 expression differs between primary and metastatic
human breast tumors and between breast cancer subtypes. DESIGN: P-Rex1 expression
was measured in 133 specimens by immunohistochemistry: 40 and 42 primary breast
tumors from patients who did versus did not develop metastasis, respectively, and
51 breast-derived tumors from metastatic sites (36 of which had matching primary
tumors available for analysis). RESULTS: Primary breast tumors showed significant
differences in P-Rex1 expression based on receptor subtype. ER+ and HER2+ primary
tumors showed higher P-Rex1 expression than primary triple-negative tumors. HER2+
metastases from all sites showed significantly higher P-Rex1 expression compared
to other metastatic receptor subtypes. Solid organ (i.e., brain, lung, and liver)
metastases showed higher P-Rex1 expression compared to bone metastases.
CONCLUSIONS: P-Rex1 expression is increased in ER+ and HER2+ breast cancers
compared to triple-negative tumors. P-Rex1 may be differentially expressed in
metastatic tumors based on site and receptor status. The role of P-Rex1 in the
development of breast cancer metastases and as a predictive biomarker of
therapeutic response warrants further investigation.
PMID- 28698811
TI - Erratum to "A Novel Nonsense Mutation of POU4F3 Gene Causes Autosomal Dominant
Hearing Loss".
AB - [This corrects the article DOI: 10.1155/2016/1512831.].
PMID- 28698810
TI - Circadian Rhythms in Fear Conditioning: An Overview of Behavioral, Brain System,
and Molecular Interactions.
AB - The formation of fear memories is a powerful and highly evolutionary conserved
mechanism that serves the behavioral adaptation to environmental threats.
Accordingly, classical fear conditioning paradigms have been employed to
investigate fundamental molecular processes of memory formation. Evidence
suggests that a circadian regulation mechanism allows for a timestamping of such
fear memories and controlling memory salience during both their acquisition and
their modification after retrieval. These mechanisms include an expression of
molecular clocks in neurons of the amygdala, hippocampus, and medial prefrontal
cortex and their tight interaction with the intracellular signaling pathways that
mediate neural plasticity and information storage. The cellular activities are
coordinated across different brain regions and neural circuits through the
release of glucocorticoids and neuromodulators such as acetylcholine, which
integrate circadian and memory-related activation. Disturbance of this interplay
by circadian phase shifts or traumatic experience appears to be an important
factor in the development of stress-related psychopathology, considering these
circadian components are of critical importance for optimizing therapeutic
approaches to these disorders.
PMID- 28698812
TI - Treatment of Community-Acquired Pneumonia: A Case Report and Current Treatment
Dilemmas.
AB - Resistance to macrolides is rising in the USA and warrants careful consideration
when confronted with a patient with suspected pneumonia in the urgent care
clinic. This case study exemplifies the potentially serious consequences of
treatment failure following prescription of a macrolide for community-acquired
bacterial pneumonia. Furthermore, the consequential treatment dilemmas currently
faced by physicians are briefly discussed.
PMID- 28698813
TI - Macroscopic Hematuria due to Placenta Percreta: Report of Two Cases and Short
Review.
AB - Herein we present two cases of pregnant women with placenta percreta and severe
hematuria during the 24th and 35th weeks of pregnancy, respectively. A timely
sonographic diagnosis was feasible in the first case and cesarean section was
performed during the 29th week. During the operation, the placenta was invading
the bladder wall and concomitant hysterectomy with cystotomy and bladder wall
reconstruction was performed. The second case presented in our emergency
department with vaginal bleeding during the 35th weeks of pregnancy. She
underwent an emergency cesarean section with uterine preservation, cystotomy, and
bladder reconstruction.
PMID- 28698814
TI - A Patient-Matched Entire First Metacarpal Prosthesis in Treatment of Giant Cell
Tumor of Bone.
AB - Giant cell tumor of the bones occurring in the first metacarpals frequently
requires entire metacarpal resection due to the aggressive nature and high rate
of recurrence. Bone reconstruction can be performed with autogenous bone grafts.
Here we describe a new technique of reconstruction using a patient-matched three
dimensional printed titanium first metacarpal prosthesis. This prosthesis has a
special design for ligament reconstruction in the proximal and distal portions.
Good hand function and aesthetic appearance were maintained at a 24-month follow
up visit. This reconstructive technique can avoid donor-site complications and
spare the autogenous bone grafts for revision options.
PMID- 28698815
TI - Glomangioma of the Kidney: A Rare Case of Glomus Tumor and Review of the
Literature.
AB - BACKGROUND: Glomus tumors are rare mesenchymal tumors originating from glomus
bodies in the skin. Glomus tumors of the kidney are rare tumors and only a few
cases have been reported in the medical literature. An extensive search revealed
a very limited number of primary renal glomus tumors. Although most of these
cases were benign in nature, including a case with uncertain diagnosis of
malignant potential, two were malignant. CASE REPORT: We present a unique case of
a 57-year-old male patient with an incidentally discovered 2 cm left renal mass.
Histopathology examination and immunohistochemical studies confirm the diagnosis
of glomangioma (a form of glomus tumor). The patient was followed for one year
after partial nephrectomy and showed a benign course without any evidence of
local recurrence or metastasis. CONCLUSION: To the best of our knowledge, this is
the 16th case of primary benign renal glomus tumors. Primary renal glomus tumors
are rare and may mimic other mesenchymal renal neoplasms radiologically. Proper
investigation (including histopathological analysis and immunohistochemical
staining) of kidney tumors is essential to make the diagnosis of glomus tumors,
which usually show a benign clinical course following resection.
PMID- 28698816
TI - Lower Extremity Abscess Formation in Premature Infants due to Routine Infant
Vaccinations.
AB - Since the introduction of vaccines, the impact of vaccinations has been
immeasurable. Under the current immunization guidelines, infants receive the
first of their routine infant vaccinations at 2 months of age. While the benefits
of routine infant vaccinations in premature infants have been demonstrated, there
is relatively little data on the dosing of these vaccines in premature infants.
The medical records of two premature infants who developed intramuscular
abscesses after receiving their routine infant vaccinations were reviewed. Both
patients developed pain in the area of the injection after receiving their
vaccinations. Magnetic resonance imaging findings confirmed the formation of an
abscess. No other causes of abscess formation were observed. Both patients
required surgical intervention and were treated with a course of antibiotics. To
our knowledge, this is the first case report to suggest routine vaccinations as a
potential cause of abscess formation in premature infants.
PMID- 28698817
TI - The fabrication of biomimetic biphasic CAN-PAC hydrogel with a seamless
interfacial layer applied in osteochondral defect repair.
AB - Cartilage tissue engineering based on biomimetic scaffolds has become a rapidly
developing strategy for repairing cartilage defects. In this study, a biphasic
CAN-PAC hydrogel for osteochondral defect (OCD) regeneration was fabricated based
on the density difference between the two layers via a thermally reactive, rapid
cross-linking method. The upper hydrogel was cross-linked by CSMA and NIPAm, and
the lower hydrogel was composed of PECDA, AAm and PEGDA. The interface between
the two layers was first grafted by the physical cross-linking of calcium
gluconate and alginate, followed by the chemical cross-linking of the carbon
carbon double bonds in the other components. The pore sizes of the upper and
lower hydrogels were ~187.4 and ~112.6 MUm, respectively. The moduli of the upper
and lower hydrogels were ~0.065 and ~0.261 MPa. This prepared bilayer hydrogel
exhibited the characteristics of mimetic composition, mimetic structure and
mimetic stiffness, which provided a microenvironment for sustaining cell
attachment and viability. Meanwhile, the biodegradability and biocompatibility of
the CAN-PAC hydrogel were examined in vivo. Furthermore, an osteochondral defect
model was developed in rabbits, and the bilayer hydrogels were implanted into the
defect. The regenerated tissues in the bilayer hydrogel group exhibited new
translucent cartilage and repaired subchondral bone, indicating that the hydrogel
can enhance the repair of osteochondral defects.
PMID- 28698818
TI - The association between the baseline bone resorption marker CTX and incident
dysglycemia after 4 years.
AB - Bone is an endocrine organ involved in modulating glucose homeostasis. The role
of the bone formation marker osteocalcin (OCN) in predicting diabetes was
reported, but with conflicting results. No study has explored the association
between baseline bone resorption activity and incident diabetes or prediabetes
during follow-up. Our objective was to examine the relationship between the
baseline bone resorption marker crosslinked C-telopeptide of type I collagen
(CTX) and glycemic dysregulation after 4 years. This longitudinal study was
conducted in a university teaching hospital. A total of 195 normal glucose
tolerant (NGT) women at baseline were invited for follow-up. The incidence of
diabetes and prediabetes (collectively defined as dysglycemia) was recorded. A
total of 128 individuals completed the 4-year study. The overall conversion rate
from NGT to dysglycemia was 31.3%. The incidence of dysglycemia was lowest in the
middle tertile [16.3% (95% confidence interval (CI), 6.8%-30.7%)] compared with
the lower [31.0% (95% CI, 17.2%-46.1%)] and upper [46.5% (95% CI, 31.2%-62.6%)]
tertiles of CTX, with a significant difference seen between the middle and upper
tertiles (P=0.002 5). After adjusting for multiple confounding variables, the
upper tertile of baseline CTX was associated with an increased risk of incident
dysglycemia, with an odds ratio of 7.09 (95% CI, 1.73-28.99) when the middle
tertile was the reference. Osteoclasts actively regulate glucose homeostasis in a
biphasic model that moderately enhanced bone resorption marker CTX at baseline
provides protective effects against the deterioration of glucose metabolism,
whereas an overactive osteoclastic function contributes to an increased risk of
subsequent dysglycemia.
PMID- 28698819
TI - The effects of melatonin on bovine uniparental embryos development in vitro and
the hormone secretion of COCs.
AB - Melatonin is a unique multifunctional molecule that mediates reproductive
functions in animals. In this study, we investigated the effects of melatonin on
bovine parthenogenetic and androgenetic embryonic development, oocyte maturation,
the reactive oxygen species (ROS) levels in parthenogenetic and androgenetic
embryos and cumulus-oocyte complexes (COCs) hormone secretion with melatonin
supplementation at four concentrations (0, 10, 20, and 30 pmol/mL), respectively.
The results showed that melatonin significantly promoted the rates of bovine
parthenogenetic and androgenetic embryonic cleavage and morula and blastocysts
development (P < 0.05). The rate of cleavage was higher in the androgenetic
embryo than that in the parthenogenetic embryo. Compared with the parthenogenetic
embryos, the androgenetic embryos had a poor developmental competence from morula
to blastocyst stage. Moreover, the levels of ROS were significantly lower in the
parthenogenetic and androgenetic embryoes with melatonin-treated group than that
of the control group (P < 0.05). Melatonin supplemented significantly increased
the maturation rate of oocyte in vitro (P < 0.05). More importantly, melatonin
significantly promoted the secretion of progesterone and estradiol by COCs (P <
0.05). To reveal the regulatory mechanism of melatonin on steroids synthesis, we
found that steroidogenic genes (CYP11A1, CYP19A1 and StAR) were upregulated,
suggesting that melatonin regulated estradiol and progesterone secretion through
mediating the expression of steroidogenic genes (CYP11A1, CYP19A1 and StAR). In
addition, MT1 and MT2 were identified in bovine early parthenogenetic and
androgenetic embryos using western blot. It could be concluded that melatonin had
beneficial effects on bovine oocyte in vitro maturation, COC hormone secretion,
early development of subsequent parthenogenetic and androgenetic embryos. It is
inferred that melatonin could be used to enhance the efficiency of in vitro
developed embryos.
PMID- 28698820
TI - Zooplankton as a potential vector for white band disease transmission in the
endangered coral, Acropora cervicornis.
AB - Coral diseases are a leading factor contributing to the global decline of coral
reefs, and yet mechanisms of disease transmission remain poorly understood. This
study tested whether zooplankton can act as a vector for white band disease (WBD)
in Acropora cervicornis. Natural zooplankton communities were collected from a
coral reef in Bocas del Toro, Panama. Half of the zooplankton were treated with
antibiotics for 24 h after which the antibiotic-treated and non-antibiotic
treated zooplankton were incubated with either seawater or tissue homogenates
from corals exhibiting WBD-like symptoms. A total of 15 of the 30 asymptomatic A.
cervicornis colonies exposed to zooplankton incubated in disease homogenate in
tank-based experiments showed signs of WBD, regardless of prior antibiotic
incubation. These results indicate that in our experimental conditions
zooplankton were a vector for coral disease after exposure to disease-causing
pathogens. Given the importance of heterotrophy on zooplankton to coral
nutrition, this potential mode of disease transmission warrants further
investigation.
PMID- 28698821
TI - An observational descriptive survey of rosacea in the Chinese population:
clinical features based on the affected locations.
AB - BACKGROUND: There is currently no study that has evaluated the differences in
epidemiological and clinical characteristics among rosacea patients according to
different facial sites. METHODS: Clinical and demographic data were obtained from
586 rosacea patients. The patients were divided into four groups based on the
main sites involved with the rosacea lesions (full-face, cheeks, nose, or
perioral involvement). Clinical signs were measured through self-reported,
dermatologist-evaluated grading of symptoms, and physiological indicators of
epidermal barrier function. RESULTS: There were 471 (80.4%), 49 (8.4%), 52
(8.9%), and 14 (2.4%) cases in the full-face, cheek, nasal and perioral groups,
respectively. Compared with the healthy control, the full-face group had lower
water content and higher transepidermal water loss (TEWL) in the cheeks, and
chin; the perioral group had lower water content and higher TEWL in the chin;
while the nasal group had the normal water content and TEWL. Compared with the
full-face group, the nasal group had more severe phymatous changes, less severe
self-reported and dermatologist-evaluated grading of symptoms. All the patients
in the perioral or the nasal group had their first rosacea lesions start and
remain at the chin or on the nose. In the full-face group, 55.8% of patients had
their lesions start with the full face, 40.1% on the cheek, and the rest (4.1%)
on the nose. CONCLUSION: Significant differences in clinical features were
observed among rosacea patients with lesions at four different sites. The lesion
localization of each group was relatively stable and barely transferred to other
locations.
PMID- 28698822
TI - In vivo function of Pgbetaglu-1 in the release of acetophenones in white spruce.
AB - Eastern spruce budworm (Choristoneura fumiferiana Clemens) (ESBW) is a major
forest pest which feeds on young shoots of white spruce (Picea glauca) and can
cause landscape level economic and ecological losses. Release of acetophenone
metabolites, piceol and pungenol, from their corresponding glycosides, picein and
pungenin, can confer natural resistance of spruce to ESBW. A beta-glucosidase
gene, Pgbetaglu-1, was recently discovered and the encoded enzyme was
characterized in vitro to function in the release of the defensive acetophenone
aglycons. Here we describe overexpression of Pgbetaglu-1 in a white spruce
genotype whose metabolome contains the glucosylated acetophenones, but no
detectable amounts of the aglycons. Transgenic overexpression of Pgbetaglu-1
resulted in release of the acetophenone aglycons in planta. This work provides in
vivo evidence for the function of Pgbetaglu-1.
PMID- 28698823
TI - A nationwide survey of healthcare personnel's attitude, knowledge, and interest
toward renal supportive care in Taiwan.
AB - BACKGROUND: Renal supportive care (RSC) is an important option for elderly
individuals reaching end-stage renal disease; however, the frequency of RSC
practice is very low among Asian countries. We evaluated the attitude, the
knowledge, and the preference for specific topics concerning RSC among
participants who worked in different medical professions in Taiwan. METHODS: A
cross-sectional questionnaire-based survey was employed. Healthcare personnel (N
= 598) who were involved in caring for end-stage renal disease patients at more
than 40 facilities in Taiwan participated in this study. Participants were asked
about their motivation for learning about RSC, the topics of RSC they were most
and least interested in, their willingness to provide RSC, and to rate their
knowledge and perceived importance of different topics. RESULTS: The vast
majority of respondents (81.9%) were self-motivated about RSC, among whom
nephrologists (96.8%) and care facilitators (administrators/volunteers) (45%)
exhibited the highest and the least motivation, respectively (p < 0.01). Overall,
respondents indicated that they had adequate knowledge about the five pre
specified RSC topics between medical professions (p = 0.04). Medical professions
and institutional size exerted significant influence on the willingness to
provide RSC. CONCLUSIONS: Our results facilitate the understanding of the
knowledge and attitude toward different RSC topics among varied medical
professions, and can guide the design of RSC education content for healthcare
personnel.
PMID- 28698824
TI - On the tear proteome of the house mouse (Mus musculus musculus) in relation to
chemical signalling.
AB - Mammalian tears are produced by lacrimal glands to protect eyes and may function
in chemical communication and immunity. Recent studies on the house mouse
chemical signalling revealed that major urinary proteins (MUPs) are not
individually unique in Mus musculus musculus. This fact stimulated us to look for
other sexually dimorphic proteins that may-in combination with MUPs-contribute to
a pool of chemical signals in tears. MUPs and other lipocalins including odorant
binding proteins (OBPs) have the capacity to selectively transport volatile
organic compounds (VOCs) in their eight-stranded beta barrel, thus we have
generated the tear proteome of the house mouse to detect a wider pool of proteins
that may be involved in chemical signalling. We have detected significant male
biased (7.8%) and female-biased (7%) proteins in tears. Those proteins that
showed the most elevated sexual dimorphisms were highly expressed and belong to
MUP, OBP, ESP (i.e., exocrine gland-secreted peptides), and SCGB/ABP (i.e.,
secretoglobin) families. Thus, tears may have the potential to elicit sex
specific signals in combination by different proteins. Some tear lipocalins are
not sexually dimorphic-with MUP20/darcin and OBP6 being good examples-and because
all proteins may flow with tears through nasolacrimal ducts to nasal and oral
cavities we suggest that their roles are wider than originally thought. Also, we
have also detected several sexually dimorphic bactericidal proteins, thus further
supporting an idea that males and females may have adopted alternative strategies
in controlling microbiota thus yielding different VOC profiles.
PMID- 28698825
TI - The earth is flat (p > 0.05): significance thresholds and the crisis of
unreplicable research.
AB - The widespread use of 'statistical significance' as a license for making a claim
of a scientific finding leads to considerable distortion of the scientific
process (according to the American Statistical Association). We review why
degrading p-values into 'significant' and 'nonsignificant' contributes to making
studies irreproducible, or to making them seem irreproducible. A major problem is
that we tend to take small p-values at face value, but mistrust results with
larger p-values. In either case, p-values tell little about reliability of
research, because they are hardly replicable even if an alternative hypothesis is
true. Also significance (p <= 0.05) is hardly replicable: at a good statistical
power of 80%, two studies will be 'conflicting', meaning that one is significant
and the other is not, in one third of the cases if there is a true effect. A
replication can therefore not be interpreted as having failed only because it is
nonsignificant. Many apparent replication failures may thus reflect faulty
judgment based on significance thresholds rather than a crisis of unreplicable
research. Reliable conclusions on replicability and practical importance of a
finding can only be drawn using cumulative evidence from multiple independent
studies. However, applying significance thresholds makes cumulative knowledge
unreliable. One reason is that with anything but ideal statistical power,
significant effect sizes will be biased upwards. Interpreting inflated
significant results while ignoring nonsignificant results will thus lead to wrong
conclusions. But current incentives to hunt for significance lead to selective
reporting and to publication bias against nonsignificant findings. Data dredging,
p-hacking, and publication bias should be addressed by removing fixed
significance thresholds. Consistent with the recommendations of the late Ronald
Fisher, p-values should be interpreted as graded measures of the strength of
evidence against the null hypothesis. Also larger p-values offer some evidence
against the null hypothesis, and they cannot be interpreted as supporting the
null hypothesis, falsely concluding that 'there is no effect'. Information on
possible true effect sizes that are compatible with the data must be obtained
from the point estimate, e.g., from a sample average, and from the interval
estimate, such as a confidence interval. We review how confusion about
interpretation of larger p-values can be traced back to historical disputes among
the founders of modern statistics. We further discuss potential arguments against
removing significance thresholds, for example that decision rules should rather
be more stringent, that sample sizes could decrease, or that p-values should
better be completely abandoned. We conclude that whatever method of statistical
inference we use, dichotomous threshold thinking must give way to non-automated
informed judgment.
PMID- 28698826
TI - Expression, refolding and spectroscopic characterization of fibronectin type III
(FnIII)-homology domains derived from human fibronectin leucine rich
transmembrane protein (FLRT)-1, -2, and -3.
AB - The fibronectin leucine rich transmembrane (FLRT) protein family consists in
humans of 3 proteins, FLRT1, -2, and -3. The FLRT proteins contain two
extracellular domains separated by an unstructured linker. The most membrane
distal part is a leucine rich repeat (LRR) domain responsible for both cis- and
trans-interactions, whereas the membrane proximal part is a fibronectin type III
(FnIII) domain responsible for a cis-interaction with members of the fibroblast
growth factor receptor 1 (FGFR1) family, which results in FGFR tyrosine kinase
activation. Whereas the structures of FLRT LRR domains from various species have
been determined, the expression and purification of recombinant FLRT FnIII
domains, important steps for further structural and functional characterizations
of the proteins, have not yet been described. Here we present a protocol for
expressing recombinant FLRT-FnIII domains in inclusion bodies in Escherichia
coli. His-tags permitted affinity purification of the domains, which subsequently
were refolded on a Ni-NTA agarose column by reducing the concentration of urea.
The refolding was confirmed by circular dichroism (CD) and 1H-NMR. By thermal
unfolding experiments we show that a strand-strand cystine bridge has significant
effect on the stability of the FLRT FnIII fold. We further show by Surface
Plasmon Resonance that all three FnIII domains bind to FGFR1, and roughly
estimate a Kd for each domain, all Kd s being in the uM range.
PMID- 28698827
TI - Evaluating Student Attitudes: Perceptions of Interprofessional Experiences
Following Participation in a Student-Run Free Clinic.
AB - It is increasingly evident that patient health outcomes are improved when they
are treated by an effective interdisciplinary healthcare team. Many also endorse
that learning to function collaboratively in interdisciplinary settings should
start at the onset of one's medical education. Student-run free clinics, such as
the University of Central Florida College of Medicine's (UCF COM) KNIGHTS
(Keeping Neighbors In Good Health Through Service) Clinic, provide opportunities
for students to work in concert with other healthcare professionals. This study
aimed to discern whether volunteering in this setting had a positive impact on
medical students' perception of working within an interdisciplinary team. A
single survey was distributed via Qualtrics to all first and second-year medical
students (N = 248) at the UCF COM. The items of interest examined in this study
were part of a larger study described elsewhere. The mean responses on a 5-point
Likert-like scale to these survey items were recorded and compared between two
cohorts: KNIGHTS volunteers and non-volunteers. One hundred twenty-three (49.6%)
students responded to the survey and most items showed no statistically
significant difference between the two groups (p-value > 0.05). However, there
were a few items of interest that did show a significant difference. These
included KNIGHTS volunteers being much more likely to have worked with other
healthcare professionals (p < 0.001) as well as believing themselves to have a
better understanding of the role of medicine within an interprofessional team (p
= 0.016). Additionally, KNIGHTS volunteers were more likely to feel like they
understood the role of patient education (p = 0.031) and pharmacy (p = 0.040)
within an interprofessional team. Interestingly, KNIGHTS volunteers were also
more likely to believe that problem-solving skills should be learned with
students within their own discipline (p = 0.009) as well as that there is little
overlap between the roles of medical students and students from other healthcare
disciplines (p = 0.044). Still, overall results showed that both volunteers and
non-volunteers had an overall positive perception of interdisciplinary teams and
working with other healthcare professionals.
PMID- 28698828
TI - A Case of Pediatric Post-Traumatic Stress Disorder Presenting as Attention
Deficit Hyperactivity Disorder: A Case Report.
AB - In the past few years, there has been increased recognition that children, who
have faced traumatic incidences, can develop post-traumatic stress disorder
(PTSD), just like in adults. We present a case of PTSD in a 6-year-old child who
endured three surgical procedures because he was suffering from a congenital
cranial stenosis (Pfeiffer) syndrome. Because of repetitive painful episodes,
resulting from the syndrome, and then post-surgical complications, the child
developed behavioral outbursts, hypervigilence, concentration problems, and
irritability. In the past, the child was diagnosed with attention deficit
hyperactivity disorder (ADHD) in the realm of his behavioral complaints, and he
was already on stimulant medications for last one year. But there was no
remarkable effect of pharmacotherapy on child's behavior despite increasing
dosages. Ultimately the child's medical and psychiatric history was reviewed and
a diagnosis of pediatric PTSD was made. Stimulant medications were discontinued
and management was started on the lines of pediatric PTSD, resulting in a
remarkable improvement in child's psychiatric outcome.
PMID- 28698829
TI - A Brown Tumor of Tibial Diaphysis Masquerading as Malignancy.
AB - A cortical lesion of the tibial diaphysis in a young patient poses a diagnostic
challenge to the clinician. Brown tumors, although not very common, may mimic
malignancies on radiographs. Brown tumors are destructive lytic lesions of the
bone due to increased osteoclastic activity and fibroblastic proliferation in
patients with uncontrolled hyperparathyroidism (HPT). They occur after primary or
secondary HPT due to renal failure but very rarely due to vitamin D deficiency.
We report a rare case of a brown tumor of tibial diaphyses in a young female
patient mimicking a locally aggressive tumor with secondary HPT due to a severe
vitamin D deficiency. The effect of hyperparathyroidism on bone metabolism is
clinically worse in the presence of vitamin D deficiency and, hence, it
predisposes patients to brown tumors that can affect any bone in the body. They
can be managed conservatively but may require prophylactic fixation in particular
cases.
PMID- 28698830
TI - Prevalence and Predictors of Home Use of Glucometers in Diabetic Patients.
AB - BACKGROUND: Self-monitoring of blood glucose (SMBG) is a critical component of
diabetes care. However, it has been shown that use of glucometers in developing
countries such as Pakistan is limited. The aim of this study was to determine the
frequency of glucometer usage in the urban diabetic population of Karachi and to
identify variables that influenced the likelihood of practice of SMBG. METHODS: A
cross-sectional study was conducted among 567 adult diabetic patients selected at
random from the out-patient departments of multiple healthcare institutions in
Karachi categorized into two settings; Government and Private. Non-diabetics,
patients having gestational diabetes, diabetes insipidus and Cushing's syndrome
and terminally ill patients were excluded. Pearson Chi-square and Mann-Whitney U
test were applied as the primary statistical method. RESULTS: Prevalence of home
glucometer usage was 59% (n= 331). High socioeconomic status (p < 0.001),
receiving care from private institutions (p < 0.001), higher education (p <
0.001), a family history of diabetes (p =0.001), awareness regarding diabetes (p
< 0.001), having diabetes for > five years (p <0.001), and managing diabetes via
pharmacological interventions (p <0.001) (versus diet and exercise) were
significant positive predictors of glucometer usage. CONCLUSIONS: Our study
demonstrates the increasing trend in use of SMBG. Lack of awareness and cost of
glucometers were reported to be the main reasons for not practicing SMBG. Given
these factors are easily modifiable, government subsidized initiatives and
awareness programs can result in a successful public health strategy to promote
SMBG.
PMID- 28698831
TI - Effectiveness of Reverse Sural Artery Flap in the Management of Wheel Spoke
Injuries of the Heel.
AB - OBJECTIVE: Soft tissue injuries at the level of lower extremities, plantar, and
dorsal foot pose a surgical challenge for reconstructive surgeons. This kind of
injury commonly occurs when lower limbs get stuck in between the spokes of the
wheel. Reverse sural artery flap has been proven to be an effective option to
cover such defects. The aim of this study is to analyze the demographic variables
of affected individuals, technical aspects of reverse sural artery flap, quantify
the effectiveness of reverse sural artery flap among various treatment options
available, and to study the outcome of injury. METHODS: A total of 49 patients
who presented during a period of six years from January 2010 to January 2016 were
included in the study. The data was collected using patient's charts, by
interviewing the patients, and from hospital records. The patients' wounds were
prepared, examined, and the injury was graded depending upon the extent of tissue
damage. Tendon and bone defects were repaired, and wounds were closed by either
split thickness skin graft or reverse sural artery flaps. RESULTS: Children were
the most commonly affected with no conclusive gender trend. The posterolateral
part of the heel of the right foot was the most frequently injured part (69%).
Surgical interventions together with proper postoperative care and follow-up
produced very good results overall. CONCLUSION: Wheel spoke injuries of the heel
can be managed without significant morbidity if the patient presents early, the
wound is assessed properly, suitable surgical technique is utilized, and good
postoperative care is provided.
PMID- 28698832
TI - Acute Inflammatory Response During Neoadjuvant Chemotherapy for Locally Advanced
Breast Cancer: A Case Report.
AB - We report on a 56-year-old Caucasian female, diagnosed with locally advanced,
hormone-receptor-positive, and human epidermal growth factor receptor 2 (HER2)
positive cancer of the left breast. The patient received neoadjuvant chemotherapy
with adriamycin/cyclophosphamide (AC) followed by docetaxel/trastuzumab. A
partial clinical and radiographical response was documented after four cycles of
AC. Approximately one week after the first cycle of docetaxel and trastuzumab,
the patient presented with diffuse edema, erythema, and induration involving the
entire left breast. The differential diagnoses included infection, inflammatory
response/reaction to docetaxel, or cancer progression. After a multidisciplinary
review, the decision was made to stop the docetaxel and deliver neoadjuvant
radiation treatment concurrent with trastuzumab. Approximately four weeks after
radiation therapy completion, the patient underwent a left total mastectomy and
axillary dissection, with pathologic complete response (pCR) in the breast and
axillary nodal disease. After surgery, systemic therapy was resumed with
paclitaxel and trastuzumab, with a plan to start adjuvant endocrine therapy after
completion of chemotherapy. We will discuss clinical considerations in the
management of the unexpected findings of acute inflammatory response in the
breast and nodal regions during neoadjuvant chemotherapy. Associations between
intrinsic breast cancer subtype and pCR in locally advanced breast cancer will
also be reviewed.
PMID- 28698833
TI - Hiding Within the Cracks: Case Report of Rare Sutural Bone Found at the Nasion.
AB - Pathology such as skull fractures can be misdiagnosed in the presence of
anatomical variations. One variant that has had little description in the
literature are the sutural bones associated with the nasal bones. Herein, we
describe a case of a rare sutural bone at the nasion, between the bones of the
right nasal, frontal, and maxillary frontal process. To our knowledge, this is
the first report of such a variant bone in this location, and such it should be
considered by clinicians when evaluating patients for pathology in this region.
PMID- 28698834
TI - Biomarkers in renal transplantation: An updated review.
AB - Genomics, proteomics and molecular biology lead to tremendous advances in all
fields of medical sciences. Among these the finding of biomarkers as non invasive
indicators of biologic processes represents a useful tool in the field of
transplantation. In addition to define the principal characteristics of the
biomarkers, this review will examine the biomarker usefulness in the different
clinical phases following renal transplantation. Biomarkers of ischemia
reperfusion injury and of delayed graft function are extremely important for an
early diagnosis of these complications and for optimizing the treatment.
Biomarkers predicting or diagnosing acute rejection either cell-mediated or
antibody-mediated allow a risk stratification of the recipient, a prompt
diagnosis in an early phase when the histology is still unremarkable. The kidney
solid organ response test detects renal transplant recipients at high risk for
acute rejection with a very high sensitivity and is also able to make diagnosis
of subclinical acute rejection. Other biomarkers are able to detect chronic
allograft dysfunction in an early phase and to differentiate the true chronic
rejection from other forms of chronic allograft nephropathies no immune related.
Finally biomarkers recently discovered identify patients tolerant or almost
tolerant. This fact allows to safely reduce or withdrawn the immunosuppressive
therapy.
PMID- 28698835
TI - Historical perspective of cell transplantation in Parkinson's disease.
AB - Cell grafting has been considered a therapeutic approach for Parkinson's disease
(PD) since the 1980s. The classical motor symptoms of PD are caused by the loss
of dopaminergic neurons in the substantia nigra pars compacta, leading to a
decrement in dopamine release in the striatum. Consequently, the therapy of cell
transplantation for PD consists in grafting dopamine-producing cells directly
into the brain to reestablish dopamine levels. Different cell sources have been
shown to induce functional benefits on both animal models of PD and human
patients. However, the observed motor improvements are highly variable between
individual subjects, and the sources of this variability are not fully
understood. The purpose of this review is to provide a general overview of the
pioneering studies done in animal models of PD that established the basis for the
first clinical trials in humans, and compare these with the latest findings to
identify the most relevant aspects that remain unanswered to date. The main focus
of the discussions presented here will be on the mechanisms associated with the
survival and functionality of the transplants. These include the role of the
dopamine released by the grafts and the capacity of the grafted cells to extend
fibers and to integrate into the motor circuit. The complete understanding of
these aspects will require extensive research on basic aspects of molecular and
cellular physiology, together with neuronal network function, in order to uncover
the real potential of cell grafting for treating PD.
PMID- 28698836
TI - Copper as an alternative antimicrobial coating for implants - An in vitro study.
AB - AIM: To investigate osteoconductive and antimicrobial properties of a titanium
copper-nitride (TiCuN) film and an additional BONIT(r) coating on titanium
substrates. METHODS: For micro-structuring, the surface of titanium test samples
was modified by titanium plasma spray (TPS). On the TPS-coated samples, the TiCuN
layer was deposited by physical vapor deposition. The BONIT(r) layer was coated
electrochemically. The concentration of copper ions released from TiCuN films was
measured by atomic absorption spectrometry. MG-63 osteoblasts on TiCuN and
BONIT(r) were analyzed for cell adhesion, viability and spreading. In parallel,
Staphylococcus epidermidis (S. epidermidis) were cultivated on the samples and
planktonic and biofilm-bound bacteria were quantified by counting of the colony
forming units. RESULTS: Field emission scanning electron microscopy (FESEM)
revealed rough surfaces for TPS and TiCuN and a special crystalline surface
structure on TiCuN + BONIT(r). TiCuN released high amounts of copper quickly
within 24 h. These release dynamics were accompanied by complete growth
inhibition of bacteria and after 2 d, no planktonic or adherent S. epidermidis
were found on these samples. On the other hand viability of MG-63 cells was
impaired during direct cultivation on the samples within 24 h. However, high cell
colonization could be found after a 24 h pre-incubation step in cell culture
medium simulating the in vivo dynamics closer. On pre-incubated TiCuN, the
osteoblasts span the ridges and demonstrate a flattened, well-spread phenotype.
The additional BONIT(r)coating reduced the copper release of the TiCuN layer
significantly and showed a positive effect on the initial cell adhesion.
CONCLUSION: The TiCuNcoating inhibits the formation of bacterial biofilms on
orthopedic implants by influencing the "race for the surface" to the advantage of
osteoblasts.
PMID- 28698837
TI - Developing a donation after cardiac death risk index for adult and pediatric
liver transplantation.
AB - AIM: To identify objective predictive factors for donor after cardiac death (DCD)
graft loss and using those factors, develop a donor recipient stratification risk
predictive model that could be used to calculate a DCD risk index (DCD-RI) to
help in prospective decision making on organ use. METHODS: The model included
objective data from a single institute DCD database (2005-2013, n = 261).
Univariate survival analysis was followed by adjusted Cox-regressional hazard
model. Covariates selected via univariate regression were added to the model via
forward selection, significance level P = 0.3. The warm ischemic threshold was
clinically set at 30 min. Points were given to each predictor in proportion to
their hazard ratio. Using this model, the DCD-RI was calculated. The cohort was
stratified to predict graft loss risk and respective graft survival calculated.
RESULTS: DCD graft survival predictors were primary indication for transplant (P
= 0.066), retransplantation (P = 0.176), MELD > 25 (P = 0.05), cold ischemia > 10
h (P = 0.292) and donor hepatectomy time > 60 min (P = 0.028). According to the
calculated DCD-RI score three risk classes could be defined of low (DCD-RI < 1),
standard (DCD-RI 2-4) and high risk (DCD-RI > 5) with a 5 years graft survival of
86%, 78% and 34%, respectively. CONCLUSION: The DCD-RI score independently
predicted graft loss (P < 0.001) and the DCD-RI class predicted graft survival (P
< 0.001).
PMID- 28698838
TI - Tuberculosis in kidney transplant recipients: A case series.
AB - Solid organ transplant recipients have an elevated risk of tuberculosis (TB) with
high mortality. Data about TB in this population in the United States is sparse.
We present four cases of active tuberculosis in kidney transplant recipients at
our center. All patients had possible TB exposure prior to transplant and all
were diagnosed with active TB within the first year of transplant. Disseminated
TB was seen in half of the patients with extra-pulmonary TB being more common
affecting lymph nodes, pericardium, and the kidney allograft. Delay in diagnosis
from onset of symptoms ranged from fifteen days to two months. Two patients died
from TB. TB is a largely preventable and curable disease. However, challenges
remain in the diagnosis due to most recipients presenting with atypical symptoms.
Physicians should maintain a high degree of suspicion for TB to promptly diagnose
and treat post-transplant thereby minimizing complications. A review of the
literature including the epidemiology, pathogenesis, clinical presentation,
diagnosis and treatment options are discussed.
PMID- 28698839
TI - Dapsone therapy for immune thrombocytopenic purpura: old but still unfamiliar.
PMID- 28698840
TI - Hematopoietic stem cell mobilization: current status and future perspective.
PMID- 28698841
TI - Granulomatous bone marrow involvement of Hodgkin lymphoma, nodular sclerosis
type.
PMID- 28698842
TI - Hemophagocytic lymphohistiocytosis secondary to histoplasmosis.
PMID- 28698844
TI - Dapsone therapy for refractory immune thrombocytopenia patients: a case series.
AB - BACKGROUND: Dapsone has been recommended as a second-line immunosuppressive agent
for patients with immune thrombocytopenia (ITP). METHODS: We retrospectively
analyzed the efficacy and safety of dapsone therapy in patients with ITP.
RESULTS: Nine ITP patients were treated with dapsone at a dose of 50-100 mg/day
between May 2013 and March 2016. All patients were refractory to multiple
previous treatments, with a median of 7 agents (range, 4-8), and 3 patients had
undergone a previous splenectomy. The median pre-treatment platelet count was
4*109/L (range, 3-27*109/L). Only 1 patient (11.1%) responded to dapsone therapy.
No severe adverse events were observed, except for 1 case of dapsone
hypersensitivity syndrome. CONCLUSION: Although dapsone is still useful for some
patients, it may be ineffective in heavily pretreated patients with profound
thrombocytopenia.
PMID- 28698843
TI - Diagnostic approaches for inherited hemolytic anemia in the genetic era.
AB - Inherited hemolytic anemias (IHAs) are genetic diseases that present with anemia
due to the increased destruction of circulating abnormal RBCs. The RBC
abnormalities are classified into the three major disorders of membranopathies,
hemoglobinopathies, and enzymopathies. Traditional diagnosis of IHA has been
performed via a step-wise process combining clinical and laboratory findings.
Nowadays, the etiology of IHA accounts for germline mutations of the responsible
genes coding for the structural components of RBCs. Recent advances in molecular
technologies, including next-generation sequencing, inspire us to apply these
technologies as a first-line approach for the identification of potential
mutations and to determine the novel causative genes in patients with IHAs. We
herein review the concept and strategy for the genetic diagnosis of IHAs and
provide an overview of the preparations for clinical applications of the new
molecular technologies.
PMID- 28698845
TI - Intrachromosomal amplification of chromosome 21 in Korean pediatric patients with
B-cell precursor acute lymphoblastic leukemia in a single institution.
AB - BACKGROUND: Intrachromosomal amplification of chromosome 21 (iAMP21), defined as
the presence of three or more RUNX1 signals on one marker chromosome, is a
distinct cytogenetic subgroup of childhood B-cell precursor acute lymphoblastic
leukemia (BCP-ALL) that is known to have a poor prognosis when treated with
standard therapy. The aim of this study was to evaluate the clinical
characteristics of Korean children with iAMP21. METHODS: The cytogenetic data
from BCP-ALL children were reviewed. The ETV6/RUNX1 ES Dual Color Probe was used
for fluorescence in situ hybridization (FISH). RESULTS: In total, 295 children
were included. Of these, 10 patients (3.4%) had iAMP21. The median age of iAMP21
patients was 9 years, and the median value of white blood cell count was
5.09*109/L. Slow early treatment response was observed more in iAMP21 patients.
Patients with iAMP21 had a higher incidence of relapse and worse survival rates.
In patients with iAMP21, the estimated 10-year cumulative incidence of relapse
was 53.3%. The estimated 10-year event-free survival and overall survival rate
were 46.7% and 64.8%, respectively. Most cases of leukemic relapse developed in
the late period (median, 43 mo). In multivariate analysis, high risk group was
the only factor that had a significant impact on death. CONCLUSION: The existence
of iAMP21 was related to delayed treatment response and was likely to affect
increased relapse and death in the late period. Further studies are needed to
reveal its effect on BCP-ALL treatment outcomes and its role as an independent
prognostic factor.
PMID- 28698846
TI - Evaluation of the role of TAX, HBZ, and HTLV-1 proviral load on the survival of
ATLL patients.
AB - BACKGROUND: Adult T-cell leukemia/lymphoma (ATLL) is an aggressive malignancy
with very poor prognosis and short survival, caused by the human T-lymphotropic
virus type-1 (HTLV-1). The HTLV-1 biomarkers trans-activator x (TAX) and HTLV-1
basic leucine zipper factor (HBZ) are main oncogenes and life-threatening
elements. This study aimed to assess the role of the TAX and HBZ genes and HTLV-1
proviral load (PVL) in the survival of patients with ATLL. METHODS: Forty-three
HTLV-1-infected individuals, including 18 asymptomatic carriers (AC) and 25 ATLL
patients (ATLL), were evaluated between 2011 and 2015. The mRNA expression of TAX
and HBZ and the HTLV-1 PVL were measured by quantitative PCR. RESULTS:
Significant differences in the mean expression levels of TAX and HBZ were
observed between the two study groups (ATLL and AC, P=0.014 and P=0.000,
respectively). In addition, the ATLL group showed a significantly higher PVL than
AC (P=0.000). There was a significant negative relationship between PVL and
survival among all study groups (P=0.047). CONCLUSION: The HTLV-1 PVL and
expression of TAX and HBZ were higher in the ATLL group than in the AC group.
Moreover, a higher PVL was associated with shorter survival time among all ATLL
subjects. Therefore, measurement of PVL, TAX, and HBZ may be beneficial for
monitoring and predicting HTLV-1-infection outcomes, and PVL may be useful for
prognosis assessment of ATLL patients. This research demonstrates the possible
correlation between these virological markers and survival in ATLL patients.
PMID- 28698847
TI - Evaluation of a new flow cytometry based method for detection of BCR-ABL1 fusion
protein in chronic myeloid leukemia.
AB - BACKGROUND: Philadelphia chromosome, a hallmark of chronic myeloid leukemia
(CML), plays a key role in disease pathogenesis. It reflects a balanced
reciprocal translocation between long arms of chromosomes 9 and 22 involving BCR
and ABL1 genes, respectively. An accurate and reliable detection of BCR-ABL
fusion gene is necessary for the diagnosis and monitoring of CML. Previously,
many technologies, most of which are laborious and time consuming, have been
developed to detect BCR-ABL chimeric gene or chromosome. METHODS: A new flow
cytometric immunobead assay was used for detection of BCR-ABL fusion proteins and
applicability, sensitivity, reliability, efficacy and rapidity of this method was
evaluated. RESULTS: From February 2009 to January 2014, a total 648 CML patients
were investigated for the status of BCR-ABL1 protein. Among them, 83 patients
were enrolled for comparative study of BCR-ABL1 positivity by three routinely
used procedures like karyotyping, and quantitative real time PCR (RT-PCR) as well
as immunobead flow cytometry assay. BCR-ABL protein analysis was found
consistent, more sensitive (17% greater sensitivity) and reliable than the
conventional cytogenetics, as flow cytometry showed 95% concordance rate to RT
PCR. CONCLUSION: BCR-ABL fusion protein assay using a new flow cytometric
immunobead might be useful in the diagnosis and monitoring CML patients.
PMID- 28698848
TI - Treatment and response of autoimmune cytopenia occurring after allogeneic
hematopoietic cell transplantation in children.
AB - BACKGROUND: Autoimmune cytopenia (AIC) is a rare complication of allogeneic
hematopoietic cell transplantation (HCT). In this study, we reviewed the
diagnosis, treatment and response to therapy for pediatric patients with post-HCT
AIC at our institution. METHODS: Of the 292 allogeneic HCTs performed from
January, 2011 to December, 2015 at the Department of Pediatrics, The Catholic
University of Korea, seven were complicated by post-HCT AIC, resulting in an
incidence of 2.4%. RESULTS: All seven patients with post-HCT AIC had received
unrelated donor transplant. Six of seven patients had a major donor-recipient
blood type mismatch. The subtypes of AIC were as follows: immune thrombocytopenia
(ITP) 2, autoimmune hemolytic anemia (AIHA) 2, Evans syndrome 3. Median time from
HCT to AIC diagnosis was 3.6 months. All but one patient responded to first line
therapy of steroid+/-intravenous immunoglobulin (IVIG), but none achieved
complete response (CR) with this treatment. After a median duration of treatment
of 15.3 months, two patients with ITP achieved CR and five had partial response
(PR) of AIC. Five patients were treated with rituximab, resulting in the
following response: 2 CR, 2 PR, 1 no response (NR). Median time to response to
rituximab was 26 days from first infusion. All patients are alive without event.
CONCLUSION: Post-HCT AIC is a rare complication that may not resolve despite
prolonged therapy. Rapid initiation of second line agents including but not
limited to B cell depleting treatment should be considered for those that fail to
achieve CR with first line therapy.
PMID- 28698849
TI - Clinical characteristics, treatment, and outcome of primary rectal lymphoma: a
single center experience of 16 patients.
AB - BACKGROUND: The rectum is a relatively uncommon site for lymphoma compared with
other gastrointestinal sites; no consensus regarding management of primary rectal
lymphoma (PRL) has been formed due to its limited frequency. We aimed to
investigate clinical characteristics and treatment outcomes in patients with PRL
in a single center patient cohort. METHODS: We retrospectively analyzed the
results of 16 consecutive patients with PRL, identified and treated at the Asan
Medical Center, Seoul, Korea between January 1993 and December 2014. RESULTS:
These 16 patients with PRL constituted 0.8% of all non-Hodgkin's lymphoma
patients (N=1,984). B-cell lymphomas (N=14) made up the majority of the series,
and half of these were extranodal marginal zone lymphomas (ENMZL, N=7). Ten
patients received systemic chemotherapy with (N=3) or without rituximab (N=7),
and 4 of these received additional local therapy. The others received
radiotherapy (N=3) or endoscopic mucosal resection (N=3). Twelve patients (75%)
achieved complete response (CR) after first-line treatment. Event-free survival
(EFS) and overall survival (OS) in stages IE and IIE were significantly longer
compared with stages IVE (P=0.001 and P=0.001, respectively). All patients with
ENMZL (N=7) achieved CR during or after initial treatment. CONCLUSION: PRL is
very rare and seems to present mostly as B-cell type. Stage is the most important
prognostic factor, with significantly better survival associated with localized
diseases. ENMZL may be one of the most common types of PRL with favorable
treatment outcomes.
PMID- 28698850
TI - Comparison of the characteristics of two hemoglobin variants, Hb D-Iran and Hb E,
eluting in the Hb A2 window.
AB - BACKGROUND: Cation exchange-high performance liquid chromatography (CE-HPLC) is
most commonly used to evaluate hemoglobin (Hb) variants, which elute in the Hb A2
window. This study aimed to assess prevalence of an uncommon Hb variant, Hb D
Iran, and compare its red cell parameters and peak characteristics with those of
Hb E that commonly elutes in the Hb A2 window. METHODS: Generally, we assess
abnormal Hb using CE-HPLC as the primary technique along with alkaline and acid
electrophoresis. All cases with Hb A2 window >9%, as assessed by CE-HPLCs during
2009-2013, were selected. RESULTS: Twenty-nine cases with Hb D-Iran variant were
identified-25 heterozygous, 2 homozygous, 1 compound heterozygous Hb D-Iran/beta
thalassemia, and 1 Hb D-Iran/Hb D-Punjab. Overall prevalence of Hb D-Iran was
0.23%. Compared to patients with Hb E, those with Hb D-Iran had significantly
higher Hb (12.1 vs. 11.3 g/dL, P=0.03), MCV (82.4 vs. 76.4 fL, P=0.0044), MCH
(27.9 vs. 25.45 pg, P =0.0006), and MCHC (33.9 vs. 33.3 g/dL, P=0.0005). Amount
of abnormal Hb (40.7 vs. 26.4%, P=0.0001) was significantly higher while
retention time (3.56 vs. 3.70 min, P=0.0001) was significantly lower in Hb D-Iran
than in Hb E. CONCLUSION: Hb D-Iran peak can be easily missed if area and
retention time of the Hb A2 window are not carefully analyzed. To distinguish
between variants, careful analysis of peak area and retention time is sufficient
in most cases and may be further confirmed by the second technique-alkaline
electrophoresis.
PMID- 28698851
TI - Impact of labile plasma iron and iron chelation on the viability of cultured
mononuclear cells from patients undergoing autologous hematopoietic stem cell
transplantation.
PMID- 28698852
TI - Acute megakaryoblastic blast crisis as a presentation manifestation of chronic
myelogenous leukemia.
PMID- 28698853
TI - Hairy cell leukemia: a case report of atypical presentation without splenomegaly.
PMID- 28698854
TI - Utility of an immunoglobulin gene rearrangement assay based on multiplex PCR in
detecting bone marrow involvement in B-cell non-Hodgkin lymphoma.
PMID- 28698855
TI - The imbalance of procoagulant and anticoagulant factors in patients with chronic
liver diseases in North India.
PMID- 28698856
TI - The first case of paroxysmal nocturnal hemoglobinuria and Budd-Chiari syndrome
treated with complement inhibitor eculizumab in Korea.
PMID- 28698857
TI - Ultrasound-guided sternal bone marrow aspiration.
PMID- 28698858
TI - Astaxanthin and beta-carotene in Helicobacter pylori-induced Gastric
Inflammation: A Mini-review on Action Mechanisms.
AB - Helicobacter pylori is a dominant bacterium living in the human gastric tissues.
In H. pylori-infected tissues, the infiltrated inflammatory cells produce
reactive oxygen species (ROS), leading to gastric inflammation with production of
various mediators. According to numerous epidemiological studies, dietary
carotenoids may prevent gastric inflammation due to their antioxidant properties.
Recent studies showed that antioxidant and anti-inflammatory effects of
astaxanthin and beta-carotene may contribute to inhibition of H. pylori-induced
gastric inflammation. Astaxanthin changes H. pylori-induced activation of T
helper cell type 1 response towards T helper cell type 2 response in the infected
tissues. Astaxanthin inhibits the growth of H. pylori. Even though astaxanthin
reduces H. pylori-induced gastric inflammation, it does not reduce cytokine
levels in the infected tissues. beta-Carotene suppresses ROS-mediated
inflammatory signaling, including mitogen-activated protein kinases and redox
sensitive transcription factors, and reduces expression of inflammatory
mediators, including interleukin-8, inducible nitric oxide synthase, and
cyclooxygenase-2 in the infected tissues. Therefore, consumption of astaxanthin-
and beta-carotene-rich foods may be beneficial to prevent H. pylori-induced
gastric inflammation. This review will summarize anti-inflammatory mechanisms of
astaxanthin and beta-carotene in H. pylori-mediated gastric inflammation.
PMID- 28698859
TI - Inflammasome as a Therapeutic Target for Cancer Prevention and Treatment.
AB - Chronic inflammation is a critical modulator of carcinogenesis through secretion
of inflammatory cytokines, which leads to the formation of an inflammatory
microenvironment. In this process, the inflammasome plays an important role in
the expression and activation of interleukin (IL)-1beta and IL-18 to promote
cancer development. The inflammasome is a multiprotein complex consisting of
several nucleotide-binding domain and leucine-rich repeat containing receptor,
adaptor proteins, and caspase 1 (CASP1). It senses the various intracellular
(damage-associated molecular patterns) and extracellular (pathogen-associated
molecular patterns) stimuli. A primed inflammasome recruits adaptor proteins,
activates CASP1 to enhance the proteolytic cleavage of pro-IL-1beta and IL-18,
and sends the signal to respond to each insult. Depending on stimuli and cell
contexts, several inflammasomes are closely associated with the initiation and
promotion of carcinogenesis. In contrast, inflammasomes also show an ambivalent
effect on carcinogenesis by enhancing inflammatory cell death (pyroptosis) and
repairing damaged tissues. Although the inflammasome plays a controversial role
in carcinogenesis, it may be a promising target for human cancer prevention and
treatment. A more in-depth study on the role of the inflammasome in
carcinogenesis, based on stimuli, cell contexts, and cancer stages, can lead to
the development of novel therapeutic strategies against malignant human cancers.
PMID- 28698860
TI - Genomic Profiling of Chronic Myelogenous Leukemia: Basic and Clinical Approach.
AB - Chronic myeloid leukemia (CML) is a hematological stem cell cancer driven by BCR
ABL1 fusion protein. We review the previous and recent evidence on the
significance of CML in diagnostic and clinic management. The technical monitoring
of BCR-ABL1 with quantitative real time-PCR has been used in assessing patient
outcome. The cytogenetic mark of CML is Philadelphia chromosome, that is formed
by reciprocal chromosomal translocations between human chromosome 9 and 22,
t(9:22) (q34:q11). It makes a BCR-ABL1 fusion protein with an anomaly tyrosine
kinase activity that promotes the characteristic proliferation of progenitor
cells in CML and acute lymphoblastic lymphoma. The targeting of BCR-ABL1 fusion
kinase is the first novel paradigm of molecularly targeted curing.
PMID- 28698861
TI - Spiritual Therapy in Coping with Cancer as a Complementary Medical Preventive
Practice.
AB - There are many of methods of treating cancer. However, the concept of curing the
cancer is beyond our current knowledge. Some patients who have the cancer may
seek an alternative manner of curing their disease. Alternative medicines, such
as spiritual and complementary therapy, are able to cure the cancer and, at the
least, are safe. Research on the importance of spirituality in cancer care has
mainly been performed in geographically heterogeneous populations. The results
are limited to these specific religious-cultural contexts and enlightened by
contributions from ethnicity and religion. This article focused on the
religiousness and spiritual support of cancer patients from diverse and
heterogeneous groups around the globe. An electronic search of peer-reviewed
articles was systematically performed to obtain the relevant literature with the
CINAHL, PsycINFO, and PubMed databases. The keywords included religion, cancer,
illness, psychotherapy, and spiritual and alternative treatment/therapies. The
inclusion criteria for the reviews were that the documents were original
quantitative research and published in English. Articles that were not directly
relevant to the present objective were excluded. The present outcome of these
review resources suggest that it may be helpful for clinicians to address
spirituality, particularly with regard to prevention, healing, and survival of
cancer patients. This article indicates that it may be useful for clinical
oncologists to be informed of the prevalence of the use of spiritual medicine in
their specialized field. In addition, patients should routinely be asked about
the use of spiritual medicine as part of every cancer patient's evaluation.
PMID- 28698862
TI - Antimutagenic and Antioxidant Activities of Thai Rice Brans.
AB - BACKGROUND: Rice bran is the outer layer of the rice grain, and contains high
amounts of bioactive phytochemicals. Here, we investigated and compared
chemopreventive properties of purple and white rice bran extracts. METHODS: Rice
bran was extracted with dichloromethane and methanol. Chemical constituents in
the extracts were analyzed by colorimetric assay and high performance liquid
chromatography. The mutagenicity and antimutagenicity of the extracts were
determined via the Salmonella mutation assay. The anticarcinogenic enzyme
induction and antioxidant activities of the extracts were examined using
Hepa1c1c7 cells and 2,2-diphenyl-1-picrylhydrazyl radical scavenging assay,
respectively. RESULTS: The methanol extracts of rice bran contained high amounts
of phenolic acids, flavonoids, anthocyanins, and phytic acid, whereas large
amounts of gamma-oryzanol and vitamin E were presented in the dichloromethane
extract. None of the extracts were mutagenic to Salmonella typhimurium. All rice
bran extracts had strong antimutagenic effects against aflatoxin B1- and 2-amino
3,4-dimethylimidazo [4,5-f]quinoline-induced mutagenesis. The inhibitory effect
against 2-aminofluorene-induced mutagenesis was found in the dichloromethane
extract, while only the methanol extract of purple rice bran exhibited
antimutagenic effects against benzo(a)pyrene. None of the extracts induced
quinone reductase activity in Hepa1c1c7 cells. Additionally, the greatest
antioxidant capacity was found in the methanol extract of purple rice bran.
CONCLUSIONS: The methanol extract of purple rice bran containing high amount of
phenolic acids, flavonoids, anthocyanins, and phytic acid showed the most
effective antioxidant and antimutagenic activities by inhibiting mutagenic
metabolizing enzymes and/or scavenging free radicals. These results demonstrate
the nutritional and medical value of Thai rice for cancer prevention.
PMID- 28698863
TI - Evaluation of the Expression of the Inhibitor of Apoptosis Protein Family and
Human Telomerase Reverse Transcriptase in Patients With Advanced Colorectal
Adenoma.
AB - BACKGROUND: It has been reported that the expression of the inhibitor of
apoptosis protein (IAP) family increases in patients with colon cancer. We
evaluated the expression of the IAP family and human telomerase reverse
transcriptase (hTERT) in normal colon mucosa from patients with advanced
colorectal adenoma and investigated their features according to characteristics
of advanced colorectal adenoma. METHODS: While resections of polyps were
performed in patients (n = 80) diagnosed with advanced colorectal adenoma or
carcinoma in situ, additional normal tissues were obtained from the sigmoid
colon. In healthy patients (n = 16), blind biopsies were performed on the sigmoid
colon. The expression of the IAP family, including survivin, XIAP, cIAP1, and
cIAP2, and hTERT, were analyzed by real-time PCR in both groups. RESULTS: A total
of 80 advanced colorectal adenoma patients (71.3% male, mean age of 60.4 years)
and 16 control patients were enrolled in this study. The mean ranking of cIAP2
was higher in the control group (68.88 vs. 44.43, P = 0.001). The expression
levels of hTERT, survivin, XIAP, and cIAP from both groups showed no differences.
The expression of survivin, XIAP, cIAP1, cIAP2, and hTERT depending on certain
factors of advanced adenoma, including the number (two or fewer vs. three or
more), size (smaller than 1 cm vs. larger than 1 cm), grade of dysplasia (low
grade adenoma vs. high grade adenoma), pathology (tubular adenoma vs. villous
adenoma), and presence of endometrial intraepithelial neoplasms, showed no
significant correlations in the Mann-Whitney U-test. CONCLUSIONS: The expression
of the IAP family and hTERT, except cIAP2, in the normal mucosa of patients with
advanced colorectal adenoma were not different from those of the control group.
There were no differences in the IAP family and hTERT according to the
characteristics of advanced adenoma.
PMID- 28698864
TI - Prevalence, Age Distribution, and Risk Factors of Visual Inspection With Acetic
Acid-Positive From 2007 to 2011 in Jakarta.
AB - BACKGROUND: Cervical cancer is still the second most frequent cancer among
Indonesian women, thus screening program is still critically important to prevent
it. Visual inspection with acetic acid (VIA) was introduced as a method which is
most suitable with Indonesia's condition compared with the other screening
methods. The Female Cancer Program from Jakarta Regional collaborated with Leiden
University in 2007 to 2011 has done cervical cancer screening using VIA method,
involving 25,406 women spreading across several primary health centers in
Jakarta. By using these data, we found out the prevalence, age distribution, and
risk factor of VIA positive in Jakarta as a basis to predict the budget and
logistics for the next cervical cancer screening and to do an advocating to the
Jakarta's government. METHODS: A secondary data analysis was conducted from
several areas in Jakarta from 2007 to 2011. VIA test was used as the screening
method, and performed by doctors and midwives with technical supervision by
gynecologists. RESULTS: From 25,406 women, there were 1,192 cases (4.7%) of VIA
test positive. The risk factors that can significantly influence the result of
VIA positive were number of marriage, parity, smoking habits, and the use of
hormonal contraception with OR 1.51, 1.85, 1.95, and 0.68, respectively.
CONCLUSIONS: Prevalence of VIA test-positive is 4.7% in Jakarta population. The
findings of precancerous lesions and cervical cancers are not only between thirty
and fifty years old, but also below the thirty years old and after fifty years
old. We suggest that VIA test should be performed to all reproductive age and
elder women who are not screened yet.
PMID- 28698865
TI - Comparisons of Gut Microbiota Among Healthy Control, Patients With Conventional
Adenoma, Sessile Serrated Adenoma, and Colorectal Cancer.
AB - BACKGROUND: Studies on gut microbiota regarding colorectal carcinogenesis,
including sessile serrated adenoma (SSA), have been scarce. The aim of this study
is to investigate the role of mucosa-associated gut microbiota in the colorectal
carcinogenesis. METHODS: We collected biopsy samples of normal rectal mucosa
during colonoscopy from healthy control and patients with conventional adenoma,
SSA, and colorectal cancer (CRC), respectively (n = 6). Pyrosequencing for 16S
rRNA gene of bacteria was performed to compare gut microbiota. RESULTS: The most
abundant phylum in total samples was Proteobacteria (55.6%), followed by
Firmicutes (27.4%) and Bacteroidetes (11.6%). There was no significant difference
in relative abundance of the phylum level among the four groups. Fusobacterium
nucleatum, known to be frequently detected during colorectal carcinogenesis, was
found in only one sample of patient with SSA. The rarefaction curves showed that
the diversity of mucosal communities of patients with CRC is the lowest among the
four groups and the diversity of mucosal communities of patients with SSA is
higher than that of healthy control. Among the four groups, Shannon's and
Simpson's index for diversity was the lowest and the highest in the patients with
CRC, respectively; it did not reach statistical significance. The proportion of
genus Pseudomonas was very high in the samples of patients with stage II-IV CRC
compared with those with stage I CRC (59.3% vs. 0.3%, P = 0.064). CONCLUSIONS:
Our study suggests no significant role of mucosa-associated gut microbiota in the
colorectal carcinogenesis. Further study for many samples or using fecal material
could be helpful.
PMID- 28698866
TI - Analysis of Gastric Body Microbiota by Pyrosequencing: Possible Role of Bacteria
Other Than Helicobacter pylori in the Gastric Carcinogenesis.
AB - BACKGROUND: Gastric microbiota along with Helicobacter pylori (HP) plays a key
role in gastric disease. The aim of our study is to investigate the difference of
human gastric microbiota between antrum and body according to disease (control
vs. gastric cancer) and HP status. METHODS: Each antrum and body biopsy was
collected from 12 subjects at Seoul National University Bundang Hospital. Gastric
microbiota was analyzed by bar-coded 454 pyrosequencing of the 16S rRNA gene.
Twelve subjects consisted of HP-negative control (n = 2), HP-negative cancer (n =
2), HP-positive control (n = 3), and HP-positive cancer (n = 5). The analysis was
focused on non-HP urease-producing bacteria (UB) and non-HP nitrosating or
nitroreducing bacteria (NB) between antrum and body. RESULTS: Gastric body
samples showed higher diversity compared to gastric antrum mucosa samples but
there was no significant difference. The mean of operational taxonomic units was
higher in HP(-) cancer than HP(+) cancer (antrum, 273.5 vs. 228.2, P = 0.439;
body, 585.5 vs. 183.2, P = 0.053). The number of non-HP UB and non-HP NB was
higher in HP(-) cancer groups than the others. These differences were more
pronounced in the body (P = 0.051 and P = 0.081, respectively). Analysis of
overlap of non-HP UB and non-HP NB revealed the higher composition of
Streptococcus pseudopneumoniae, S. parasanguinis, and S. oralis in HP(-) cancer
groups than the others, only in the body (P = 0.030) but not in the antrum (P =
0.123). CONCLUSIONS: Higher diversity and higher composition of S.
pseudopneumoniae, S. parasanguinis, and S. oralis in HP(-) cancer group than the
other groups in the body suggest that analysis of microbiota from body mucosa
could be beneficial to identify a role of non-HP bacteria in the gastric
carcinogenesis.
PMID- 28698867
TI - The Effect of Osteopontin on Microglia.
AB - Osteopontin (OPN) is a proinflammatory cytokine that can be secreted from many
cells, including activated macrophages and T-lymphocytes, and is widely
distributed in many tissues and cells. OPN, a key factor in tissue repairing and
extracellular matrix remodeling after injury, is a constituent of the
extracellular matrix of the central nervous system (CNS). Recently, the role of
OPN in neurodegenerative diseases has gradually caused widespread concern.
Microglia are resident macrophage-like immune cells in CNS and play a vital role
in both physiological and pathological conditions, including restoring the
integrity of the CNS and promoting the progression of neurodegenerative
disorders. Microglia's major function is to maintain homeostasis and the normal
function of the CNS, both during development and in response to CNS injury.
Although the functional mechanism of OPN in CNS neurodegenerative diseases has
yet to be fully elucidated, most studies suggest that OPN play a role in
pathogenesis of neurodegenerative diseases or in neuroprotection by regulating
the activation and function of microglia. Here, we summarize the functions of OPN
on microglia in response to various stimulations in vitro and in vivo.
PMID- 28698868
TI - Diagnostic MicroRNA Biomarker Discovery for Non-Small-Cell Lung Cancer
Adenocarcinoma by Integrative Bioinformatics Analysis.
AB - Lung cancer is the leading cause of cancer death and its incidence is ranked high
in men and women worldwide. Non-small-cell lung cancer (NSCLC) adenocarcinoma is
one of the most frequent histological subtypes of lung cancer. The aberration
profile and the molecular mechanism driving its progression are the key for
precision therapy of lung cancer, while the screening of biomarkers is essential
to the precision early diagnosis and treatment of the cancer. In this work, we
applied a bioinformatics method to analyze the dysregulated interaction network
of microRNA-mRNA in NSCLC, based on both the gene expression data and the
microRNA-gene regulation network. Considering the properties of the substructure
and their biological functions, we identified the putative diagnostic biomarker
microRNAs, some of which have been reported on the PubMed citations while the
rest, that is, miR-204-5p, miR-567, miR-454-3p, miR-338-3p, and miR-139-5p, were
predicted as the putative novel microRNA biomarker for the diagnosis of NSCLC
adenocarcinoma. They were further validated by functional enrichment analysis of
their target genes. These findings deserve further experimental validations for
future clinical application.
PMID- 28698869
TI - Effects of Poly(ADP-Ribose) Polymerase-1 Inhibition in a Neonatal Rodent Model of
Hypoxic-Ischemic Injury.
AB - BACKGROUND: Hypoxia ischemia (HI) to the developing brain occurs in 1-6 in 1000
live births. Large numbers of survivors have neurological long-term sequelae.
However, mechanisms of recovery after HI are not understood and preventive
measures or clinical treatments are not effective. Poly(ADP-ribose) polymerase-1
is overactivated in response to ischemia. In neonatal mice HI activates PARP-1
but its role in perinatal brain injury remains uncertain. OBJECTIVE: Aim of this
study was to explore the effect of TES448 (PARP-1-inhibitor) and hypothermia
after an ischemic insult. DESIGN AND METHODS: 10-day-old Wistar rats underwent
HI. TES448 was given 10 min, 3 hrs, and 6 hrs after hypoxia. Hypothermia was
started 30 min after HI and brains were dissected at P12. Western blotting and
histological staining were used to evaluate for degree of injury. RESULTS:
Protein expression of PARP-1 levels was diminished after TES448 treatment. Cresyl
violet and TUNEL staining revealed decreased injury in male rat pups following
TES448 and combined treatment. Female rats showed increased numbers of TUNEL
positive cells after combined therapy. TES448 inhibited microglia activation
after hypoxic-ischemic injury. A cellular response including NeuN, Olig2, and MBP
was not affected by PARP-1-inhibition. CONCLUSIONS: Inhibition of PARP-1 and
hypothermia lead to an alteration of injury but this effect is sexually
dimorphic.
PMID- 28698870
TI - Current Status and Future Perspective of Stenting for Symptomatic Intracranial
Atherosclerotic Disease: A Meta-Analysis.
AB - The aim of this study was to evaluate the safety and effectiveness of
percutaneous transluminal angioplasty and stenting (PTAS) for intracranial
atherosclerotic disease (ICAD) by conducting a meta-analysis. Two independent
observers searched PubMed, EMBASE, and Cochrane Library for relevant studies up
to 31 December 2016. A meta-analysis was conducted using Review Manager 5.3.
Three studies involving 581 cases were included. The meta-analysis indicated that
any stroke (RR = 3.13; 95% CI: 1.80-5.42), ischemic stroke (RR = 2.15; 95% CI:
1.19-3.89), and intracranial hemorrhage (RR = 14.71; 95% CI: 1.96-110.48) within
30 days in medical therapy alone were lower compared with PTAS plus medical
therapy, but there were no significant differences in any stroke and ischemic
stroke beyond 30 days between the two groups. There were also no significant
differences in any death and myocardial infarction between the two groups. This
meta-analysis demonstrated that, compared with medical therapy alone, PTAS for
ICAD had a high risk of complication, but most complications in PTAS group
occurred within 30 days after the operation, and beyond 30 days the PTAS was not
inferior compared with medical therapy alone. Further studies are needed to
reduce the periprocedural complications and reappraise the PTAS.
PMID- 28698871
TI - Comparison of Minimally Invasive Percutaneous Plate Osteosynthesis and Open
Reduction Internal Fixation on Proximal Humeral Fracture in Elder Patients: A
Systematic Review and Meta-Analysis.
AB - OBJECTIVE: The study aims to compare minimally invasive percutaneous plate
osteosynthesis (MIPO) and open reduction internal fixation (ORIF) in the
treatment of proximal humeral fracture in elder patients. METHOD: PubMed,
Medline, EMbase, Ovid, Cochrane Library, China National Knowledge Infrastructure
(CNKI), Wangfang, and VIP Database for Chinese Technical Periodicals were
searched to identify all relevant studies from inception to October 2016. Data
were analyzed with Cochrane Collaboration's Review Manage 5.2. RESULTS: A total
of 630 patients from 8 publications were included in the systematic review and
meta-analysis. The pooled results showed that MIPO was superior to ORIF in the
treatment of proximal humeral fracture in elder patients. It was reflected in
reducing blood loss, operation time, postoperative pain, or fracture healing time
of the surgery and in improving recovery of muscle strength. Concerning
complications, no significant difference was seen between MIPO and ORIF.
CONCLUSION: The MIPO was more suitable than ORIF for treating proximal humeral
fracture in elder patients.
PMID- 28698872
TI - Proliferation of Interstitial Cells in the Cyclophosphamide-Induced Cystitis and
the Preventive Effect of Imatinib.
AB - Cyclophosphamide- (CYP-) induced cystitis in the rat is a well-known model of
bladder inflammation that leads to an overactive bladder, a process that appears
to involve enhanced nitric oxide (NO) production. We investigated the changes in
the number and distribution of interstitial cells (ICs) and in the expression of
endothelial NO synthase (eNOS) in the bladder and urethra of rats subjected to
either intermediate or chronic CYP treatment. Pronounced hyperplasia and
hypertrophy of ICs were evident within the lamina propria and in the muscle
layer. IC immunolabeling with CD34, PDGFRalpha, and vimentin was enhanced, as
reflected by higher colocalization indexes of the distinct pairs of markers.
Moreover, de novo expression of eNOS was evident in vimentin and CD34 positive
ICs. Pretreatment with the receptor tyrosine kinase inhibitor Imatinib prevented
eNOS expression and ICs proliferation, as well as the increased voiding frequency
and urinary tract weight provoked by CYP. As similar results were obtained in the
urethra, urethritis may contribute to the uropathology of CYP-induced cystitis.
PMID- 28698873
TI - Epidemiological Distribution and Subtype Analysis of Premenstrual Dysphoric
Disorder Syndromes and Symptoms Based on TCM Theories.
AB - We performed an epidemiological investigation of subjects with premenstrual
dysphoric disorder (PMDD) to identify the clinical distribution of the major
syndromes and symptoms. The pathogenesis of PMDD mainly involves the dysfunction
of liver conveyance and dispersion. Excessive liver conveyance and dispersion are
associated with liver-qi invasion syndrome, while insufficient liver conveyance
and dispersion are expressed as liver-qi depression syndrome. Additionally, a
nonconditional logistic regression was performed to analyze the symptomatic
features of liver-qi invasion and liver-qi depression. As a result of this
analysis, two subtypes of PMDD are proposed, namely, excessive liver conveyance
and dispersion (liver-qi invasion syndrome) and insufficient liver conveyance and
dispersion (liver-qi depression syndrome). Our findings provide an
epidemiological foundation for the clinical diagnosis and treatment of PMDD based
on the identification of different types.
PMID- 28698875
TI - The Role of Interleukin-17, Interleukin-23, and Transforming Growth Factor-beta
in Pregnancy Complicated by Placental Insufficiency.
AB - AIM: The aim of the study was to evaluate the role of Interleukin-17 (IL-17),
Interleukin-23 (IL-23), and transforming growth factor-beta (TGF-beta) in
pregnancy complicated by placental insufficiency and in normal pregnancy.
MATERIAL AND METHODS: The study comprised 34 patients with pregnancy complicated
by fetal growth restriction (FGR) associated with preeclampsia (PE), as well as
35 healthy pregnant women. The concentrations of IL-17, IL-23, and TGF-beta in
sera from maternal peripheral blood were determined by an immunoenzymatic assay.
RESULTS: There were higher concentrations of IL-17 in the study group when
compared to the controls. In the group of patients with placental insufficiency,
the levels of IL-17 positively correlated with systolic blood pressure (R = 0.42,
p < 0.01). The study obtained comparable concentrations of IL-23 in both studied
groups. The concentrations of TGF-beta were significantly lower in pregnancy
complicated by the insufficiency of placenta when compared to the controls.
CONCLUSIONS: It seems possible that the increased concentrations of IL-17 and the
deficiency of TGF-beta in pregnancy complicated by FGR and PE can be responsible
for the activation of inflammatory response observed in PE cases.
PMID- 28698874
TI - Preclinical Studies and Translational Applications of Intracerebral Hemorrhage.
AB - Intracerebral hemorrhage (ICH) which refers to bleeding in the brain is a very
deleterious condition with high mortality and disability rate. Surgery or
conservative therapy remains the treatment option. Various studies have divided
the disease process of ICH into primary and secondary injury, for which knowledge
into these processes has yielded many preclinical and clinical treatment options.
The aim of this review is to highlight some of the new experimental drugs as well
as other treatment options like stem cell therapy, rehabilitation, and
nanomedicine and mention some translational clinical applications that have been
done with these treatment options.
PMID- 28698876
TI - Standard versus Minimally Invasive Transforaminal Lumbar Interbody Fusion: A
Prospective Randomized Study.
AB - Symptomatic spondylolisthesis patients may benefit from surgical decompression
and stabilization. The standard (S) technique is a transforaminal lumbar
interbody fusion (TLIF). Newer, minimally invasive (MI) techniques seem to
provide similar results with less morbidity. We enrolled patients with at least 6
months of symptoms and image-confirmed low-grade spondylolisthesis, at a single
academic institution, between 2011 and 2015. The patients were randomized to
either S or MI TLIF. The primary outcome measure was the Oswestry Disability
Index (ODI) improvement at 1 year. Secondary outcome measures included length of
operation, estimated blood loss, length of hospitalization, and fusion rates at 1
year. Forty patients were enrolled in each group. The differences in mean
operative time and estimated blood loss were not statistically significant
between the two groups. The patients were discharged after surgery at 4.12 days
for the S TLIF group and 1.92 days for the MI TLIF group. The ODI improvement was
similar and statistically significant in both groups. The fusion was considered
solid in 36 (90%) of patients at 1 year in both groups. In conclusion, the two
techniques provided similar clinical and radiological outcomes at 1 year. The
patients undergoing MI TLIF had a shorter hospital stay. This trial is registered
with NCT03155789.
PMID- 28698877
TI - Cancer Diagnostic and Predictive Biomarkers 2016.
PMID- 28698878
TI - Bacterial Community Profile of the Gut Microbiota Differs between
Hypercholesterolemic Subjects and Controls.
AB - The role of gut microbiota in the development of metabolic illnesses has been
abundantly demonstrated. Recent studies suggest that gut microbiota alterations
may also be related to the development of hypercholesterolemia. Therefore, we
aimed to assess differences in the gut bacterial community profiles between
hypercholesterolemic subjects and controls. Thirty cases diagnosed with
hypercholesterolemia and 27 normocholesterolemic controls were included. A
fasting whole blood sample was obtained to determine the lipid profile. In
parallel, stool samples were collected and total DNA was isolated to assess the
bacterial community profiles by denaturing gradient gel electrophoresis (DGGE).
In addition, the Richness, Shannon-Weaver, and Simpson indexes were used to
evaluate the richness and diversity of bacterial communities. As expected, serum
concentrations of total cholesterol, triglycerides, and LDL-cholesterol were
significantly higher in the cases compared with controls. Moreover, DGGE analysis
showed a lower richness and diversity of bacterial communities in
hypercholesterolemic subjects. In conclusion, our results showed differences in
the profiles of bacterial communities between hypercholesterolemic subjects and
controls, suggesting a possible role of the gut microbiota in the development of
hypercholesterolemia.
PMID- 28698879
TI - Complete Chloroplast Genome Sequence of Coptis chinensis Franch. and Its
Evolutionary History.
AB - The Coptis chinensis Franch. is an important medicinal plant from the
Ranunculales. We used next generation sequencing technology to determine the
complete chloroplast genome of C. chinensis. This genome is 155,484 bp long with
38.17% GC content. Two 26,758 bp long inverted repeats separated the genome into
a typical quadripartite structure. The C. chinensis chloroplast genome consists
of 128 gene loci, including eight rRNA gene loci, 28 tRNA gene loci, and 92
protein-coding gene loci. Most of the SSRs in C. chinensis are poly-A/T. The
numbers of mononucleotide SSRs in C. chinensis and other Ranunculaceae species
are fewer than those in Berberidaceae species, while the number of dinucleotide
SSRs is greater than that in the Berberidaceae. C. chinensis diverged from other
Ranunculaceae species an estimated 81 million years ago (Mya). The divergence
between Ranunculaceae and Berberidaceae was ~111 Mya, while the Ranunculales and
Magnoliaceae shared a common ancestor during the Jurassic, ~153 Mya. Position 104
of the C. chinensis ndhG protein was identified as a positively selected site,
indicating possible selection for the photosystem-chlororespiration system in C.
chinensis. In summary, the complete sequencing and annotation of the C. chinensis
chloroplast genome will facilitate future studies on this important medicinal
species.
PMID- 28698880
TI - Secure Screw Placement in Management of Acetabular Fractures Using the
Suprapectineal Quadrilateral Buttress Plate.
AB - Acetabular fractures involving predominantly the anterior column associated with
a disruption of the quadrilateral surface can be treated with instrumentation
implementing the stabilization of the quadrilateral surface. The recently
introduced suprapectineal quadrilateral buttress plate is specifically designed
to prevent secondary medial subluxation of the femoral head, especially in
elderly patients with reduced ability for partial weight bearing. Whereas there
are guidelines available for safe screw fixation for the anterior and posterior
columns, there might be a concern for intra-articular placement of screws placed
through the infrapectineal part of the quadrilateral buttress plate. Within this
report we analyzed retrospectively screw placement in 30 plates in postoperative
CT scans using algorithms for metal artifact reduction. None of the screws of the
buttress plate penetrated the hip joint. We describe the placement, length, and
spatial orientation of the screws used for fracture fixation and suggest that the
use of intraoperative image intensifiers with a combined inlet-obturator view of
30-45 degrees best projects the screws and the hip joint. Preoperative knowledge
of approximate screw placement and information for accurate intraoperative
imaging may contribute to safe acetabular fracture fixation and may reduce
operating time and limit radiation exposure to the patient and the personnel.
This trial is registered with KEK-BE: 266/2014.
PMID- 28698881
TI - Assessment of Haemodynamic Response to Nonselective Beta-Blockers in Portal
Hypertension by Phase-Contrast Magnetic Resonance Angiography.
AB - A significant unmet need exists for accurate, reproducible, noninvasive
diagnostic tools to assess and monitor portal hypertension (PHT). We report the
first use of quantitative MRI markers for the haemodynamic assessment of
nonselective beta-blockers (NSBB) in PHT. In a randomized parallel feasibility
study in 22 adult patients with PHT and a clinical indication for NSBB, we
acquired haemodynamic data at baseline and after 4 weeks of NSBB (propranolol or
carvedilol) using phase-contrast MR angiography (PC-MRA) in selected intra
abdominal vessels. T1 mapping of liver and spleen was undertaken to assess
changes in tissue composition. Target NSBB dose was achieved in 82%. There was a
substantial reduction from baseline in mean average flow in the superior
abdominal aorta after 4 weeks of NSBB therapy (4.49 +/- 0.98 versus 3.82 +/- 0.86
L/min, P = 0.03) but there were no statistically significant differences in flow
in any other vessels, even in patients with >25% decrease in heart rate (47% of
patients). Mean percentage change in liver and spleen T1 following NSBB was small
and highly variable. In conclusion, PC-MRA was able to detect reduction in
cardiac output by NSBB but did not detect significant changes in visceral blood
flow or T1. This trial was registered with the ISRCTN registry (ISRCTN98001632).
PMID- 28698882
TI - ExCNVSS: A Noise-Robust Method for Copy Number Variation Detection in Whole Exome
Sequencing Data.
AB - Copy number variations (CNVs) are structural variants associated with human
diseases. Recent studies verified that disease-related genes are based on the
extraction of rare de novo and transmitted CNVs from exome sequencing data. The
need for more efficient and accurate methods has increased, which still remains a
challenging problem due to coverage biases, as well as the sparse, small-sized,
and noncontinuous nature of exome sequencing. In this study, we developed a new
CNV detection method, ExCNVSS, based on read coverage depth evaluation and scale
space filtering to resolve these problems. We also developed the method
ExCNVSS_noRatio, which is a version of ExCNVSS, for applying to cases with an
input of test data only without the need to consider the availability of a
matched control. To evaluate the performance of our method, we tested it with 11
different simulated data sets and 10 real HapMap samples' data. The results
demonstrated that ExCNVSS outperformed three other state-of-the-art methods and
that our method corrected for coverage biases and detected all-sized CNVs even
without matched control data.
PMID- 28698883
TI - Anti-Platelet Factor 4/Heparin Antibody Formation Occurs Endogenously and at
Unexpected High Frequency in Polycythemia Vera.
AB - BACKGROUND: Myeloproliferative neoplasms (MPN) encounter thromboses due to
multiple known risk factors. Heparin-induced thrombocytopenia (HIT) is a
thrombotic syndrome mediated by anti-platelet factor 4 (PF4)/heparin antibodies
with undetermined significance for thrombosis in MPN. We hypothesized that anti
PF4/heparin Ab might occur in MPN and promote thrombosis. METHODS: Anti
PF4/heparin antibodies were analyzed in 127 MPN patients including 76 PV and 51
ET. Screening, validation testing, and isotype testing of anti-PF4/heparin Ab
were correlated with disease characteristics. RESULTS: Anti-PF4/heparin
antibodies were detected in 21% of PV and 12% of ET versus 0.3-3% in heparin
exposed patients. Validation testing confirmed anti-PF4/heparin immunoglobulins
in 15% of PV and 10% of ET. Isotype testing detected 9.2% IgG and 5.3% IgM in PV
and exclusively IgM in ET. IgG-positive PV patients encountered thromboses in
57.1% suggesting anti-PF4/heparin IgG may contribute to higher risk for
thrombosis in MPN. Overall, 45% of PV patients experienced thromboses with 11.8%
positive for anti-PF4/heparin IgG versus 7.1% in PV without thrombosis.
CONCLUSION: Anti-PF4/heparin antibodies occur endogenously and more frequently in
MPN than upon heparin exposure. Thrombotic risk increases in anti-PF4/heparin IgG
positive PV reflecting potential implications and calling for larger,
confirmatory cohorts. Anti-PF4/heparin IgG should be assessed upon thrombosis in
PV to facilitate avoidance of heparin in anti-PF4/heparin IgG-positive PV.
PMID- 28698884
TI - All-Cause Mortality Risk in Australian Women with Impaired Fasting Glucose and
Diabetes.
AB - AIMS: Impaired fasting glucose (IFG) and diabetes are increasing in prevalence
worldwide and lead to serious health problems. The aim of this longitudinal study
was to investigate the association between impaired fasting glucose or diabetes
and mortality over a 10-year period in Australian women. METHODS: This study
included 1167 women (ages 20-94 yr) enrolled in the Geelong Osteoporosis Study.
Hazard ratios for all-cause mortality in diabetes, IFG, and normoglycaemia were
calculated using a Cox proportional hazards model. RESULTS: Women with diabetes
were older and had higher measures of adiposity, LDL cholesterol, and
triglycerides compared to the IFG and normoglycaemia groups (all p < 0.001).
Mortality rate was greater in women with diabetes compared to both the IFG and
normoglycaemia groups (HR 1.8; 95% CI 1.3-2.7). Mortality was not different in
women with IFG compared to those with normoglycaemia (HR 1.0; 95% CI 0.7-1.4).
CONCLUSIONS: This study reports an association between diabetes and all-cause
mortality. However, no association was detected between IFG and all-cause
mortality. We also showed that mortality in Australian women with diabetes
continues to be elevated and women with IFG are a valuable target for prevention
of premature mortality associated with diabetes.
PMID- 28698885
TI - The effect of Self-Management Training on Self-Efficacy of Cirrhotic Patients
Referring to Transplantation Center of Nemazee Hospital: A Randomized Controlled
Clinical Trial.
AB - BACKGROUND: Cirrhosis is a chronic and progressive disease that causes various
complications for patients due to disturbance of the liver's usual function. Self
efficacy refers to an individual's belief in one's ability to perform the
necessary behaviors to achieve one's goals. Self-management is also an important
criterion for long-term change in behavior. The present study aimed to
investigate the effect of self-management training on self-efficacy of patients
suffering from liver cirrhosis. METHODS: This randomized controlled clinical
trial was conducted on 74 patients with liver cirrhosis randomly assigned to an
intervention (receiving self-management training) and a control group (routine
care) from 2012 to 2013. The data were collected in the transplantation center
affiliated to Shiraz University of Medical Sciences. Self-management training was
performed in six 90-minute sessions twice a week. Besides, the intervention group
was followed up for a month via telephone. Levo self-efficacy questionnaire was
filled out by the patients before, immediately after, and one month after the
intervention. Then, the data were entered into the SPSS statistical software (v.
16) and analyzed using independent t-test, Chi-square test, and repeated measures
ANOVA. RESULT: At the beginning of the study, no statistically significant
difference was found between the two groups regarding self-efficacy (P=0.18).
However, the total score of the questionnaire and those of all its dimensions
significantly improved in the intervention group immediately and one month after
training self-management skills (P<0.001). The mean score of self-efficacy was
102.24+/-7.79 and 76.78+/-9.49 in the intervention and control groups,
respectively. On the other hand, no statistically significant difference was
observed in the control group's self-efficacy immediately and one month after the
intervention (P=0.6). CONCLUSION: The results showed that the self-management
program resulted in improvement of self-efficacy in the patients with liver
cirrhosis. Therefore, this supportive strategy could be useful in patients with
chronic illnesses for improvement of care and prevention of complications.
PMID- 28698886
TI - The Prevalence, Subtypes and Obstetric Risk Factors of Urinary Incontinence in
Reproductive Age Women Referred to Community Health Care Centers of Dezful, Iran-
2015.
AB - BACKGROUND: Urinary incontinence (UI) is a common health problem and has a
profound effect on the quality of life and psychosocial aspects of the affected
women. The aim of this study was to investigate the prevalence and risk factors
of UI in reproductive age women. METHODS: This cross-sectional study was
conducted on 2000 reproductive age women from February to June 2015. The women
were selected from all of the primary health care centers of Dezful, using easy
access sampling method. Body mass index (BMI) was measured and data were
collected by demographic, detailed information regarding obstetric and
International Consultation on Incontinence Questionnaire- Urinary incontinence -
Short Form(ICIQ-SF) ICIQ-SF questionnaires. RESULTS: The women's mean age was
33.6+/-8, and 57.7% (1154) of them reported UI. The prevalence of UI subtypes was
recorded in 38.2% (441) stress UI (SUI), 44.9% (518) mixed UI, and 16.9% (195)
urge UI. There was a significant association between the mean of pregnancies,
mean of deliveries, mode of delivery, abortion, neonate>4 kg, irregular
menstruation and UI (P<0.05). Multiple logistic regression analysis showed that
age, irregular menstruation and vaginal delivery increased the risk of UI in this
age group. CONCLUSION: The findings suggest that a significant proportion of
reproductive age women were undiagnosed with UI and MUI was the most common type
of UI in this age group. Regular menstruation was a protective factor but older
age and vaginal delivery were risk factors for UI in this study.
PMID- 28698887
TI - The Psychometric Parameters of the Farsi Form of the Arabic Scale of Death
Anxiety.
AB - The aim of this study was to describe the psychometric properties of the Farsi
Form of the Arabic Scale of Death Anxiety (ASDA). The original scale was first
translated into Farsi by language experts using the back translation procedure
and then administered to a total of 252 Iranian college students and 52
psychiatric outpatients from psychiatric and psychological clinics. The one-week
test-retest reliability of the Farsi version in a sample of college students was
0.78, indicating good temporal stability and corroborating the trait-like nature
of scores. Cronbach's alpha was 0.90 for the college students and 0.92 for the
psychiatric outpatients, indicating high internal consistency. Scale scores
correlated 0.46 with Death Obsession Scale scores, 0.56 with Death Depression
Scale scores, 0.41 with Death Anxiety Scale scores, and 0.40 with Wish to be Dead
Scale scores, indicating good construct and criterion-related validity. A
principal component analysis with a Varimax rotation yielded four factors in the
sample of Iranian college students, indicating a lack of homogeneity in the
content of the scale. Male students obtained a significant higher mean score than
did females. It was concluded that the Farsi ASDA had good internal consistency,
temporal stability, criterion-related validity, and a factor structure reflecting
important features of death anxiety. In general, the Farsi ASDA could be
recommended for use in research on death anxiety among Iranian college students
and psychiatric outpatients.
PMID- 28698889
TI - Blue diode laser versus traditional infrared diode laser and quantic molecular
resonance scalpel: clinical and histological findings after excisional biopsy of
benign oral lesions.
AB - This study aims to compare the use of the innovative blue diode laser (BLUE
group) with two traditional surgical techniques: the infrared diode laser (IR
group) and the quantic molecular resonance scalpel (QMR group) in the excision of
benign oral lesions. Ninety-three patients underwent surgical excision of a
benign oral lesion and were followed up for 30 days for pain (0 to 10 visual
analogue scale), bleeding, and painkillers' assumption (yes/no). A blind
pathologist evaluated the thermal damage along the cutting margin. Although
referred pain was lowest in the BLUE group from day 7 on (p<0.05), all patients
referred minimum discomfort after surgery. The BLUE group reported minimum
bleeding and necessity of sutures (p<0.000). The QMR group showed the highest
bleeding during surgery (p<0.000), while after 14 and 30 days no patient bled.
Most of the patients in all groups did not need painkillers. The lowest thermal
damage (p<0.000) was found in the BLUE group (71.3+/-51.8???m), whereas the IR
group proved the highest (186.8+/-82.7???m) compared both with the BLUE and QMR
(111.4+/-55.4???m) groups. All the techniques allowed correct histological
sampling. All the experimented techniques offer interesting advantages, although
the blue laser minimizes risk of bleeding with limited thermal damage.
PMID- 28698888
TI - Modulation of Complex-Spike Duration and Probability during Cerebellar Motor
Learning in Visually Guided Smooth-Pursuit Eye Movements of Monkeys.
AB - Activation of an inferior olivary neuron powerfully excites Purkinje cells via
its climbing fiber input and triggers a characteristic high-frequency burst,
known as the complex spike (CS). The theory of cerebellar learning postulates
that the CS induces long-lasting depression of the strength of synapses from
active parallel fibers onto Purkinje cells, and that synaptic depression leads to
changes in behavior. Prior reports showed that a CS on one learning trial is
linked to a properly timed depression of simple spikes on the subsequent trial,
as well as a learned change in pursuit eye movement. Further, the duration of a
CS is a graded instruction for single-trial plasticity and behavioral learning.
We now show across multiple learning paradigms that both the probability and
duration of CS responses are correlated with the magnitudes of neural and
behavioral learning in awake behaving monkeys. When the direction of the
instruction for learning repeatedly was in the same direction or alternated
directions, the duration and probability of CS responses decreased over a
learning block along with the magnitude of trial-over-trial neural learning. When
the direction of the instruction was randomized, CS duration, CS probability, and
neural and behavioral learning remained stable across time. In contrast to
depression, potentiation of simple-spike firing rate for ON-direction learning
instructions follows a longer time course and plays a larger role as depression
wanes. Computational analysis provides a model that accounts fully for the
detailed statistics of a complex set of data.
PMID- 28698890
TI - Change of tumor vascular reactivity during tumor growth and postchemotherapy
observed by near-infrared spectroscopy.
AB - Breast cancer is one of the most common cancers in females. To monitor
chemotherapeutic efficacy for breast cancer, medical imaging systems such as x
ray mammography, computed tomography, magnetic resonance imaging, and ultrasound
imaging have been used. Currently, it can take up to 3 to 6 weeks to see the
tumor response from chemotherapy by monitoring tumor volume changes. We used near
infrared spectroscopy (NIRS) to predict breast cancer treatment efficacy earlier
than tumor volume changes by monitoring tumor vascular reactivity during
inhalational gas interventions. The results show that the amplitude of oxy
hemoglobin changes (vascular reactivity) during hyperoxic gas inhalation is well
correlated with tumor growth and responded one day earlier than tumor volume
changes after chemotherapy. These results may imply that NIRS with respiratory
challenges can be useful in early detection of tumor and in the prediction of
tumor response to chemotherapy.
PMID- 28698892
TI - Association between vaginal bulge and anatomical pelvic organ prolapse during
pregnancy and postpartum: an observational study.
AB - INTRODUCTION AND HYPOTHESIS: Pelvic organ prolapse (POP) is defined as the
coexistence of anatomical POP and relevant symptoms. Vaginal bulge is the symptom
most closely associated with the anatomical condition in nonpregnant women. Even
if childbearing is a major risk factor for the development of POP, there is scant
knowledge on the prevalence of specific POP symptoms, and how these symptoms
relate to anatomical POP during pregnancy and postpartum. The aim of this study
was to explore whether vaginal bulge symptoms were associated with anatomical POP
in pregnancy and postpartum, and to present the prevalence of vaginal bulge
symptoms throughout this period. METHODS: A prospective observational study was
carried out following 300 nulliparous pregnant women with repeat assessments from
mid-pregnancy until 1 year postpartum. Symptoms of vaginal bulge defined as the
sensation of a vaginal bulge inside and/or outside the vagina were assessed by
electronic questionnaires. Anatomical POP defined as pelvic organ prolapse
quantification system (POP-Q) stage >=2 has been presented in a previous
publication and showed a range of 1-9%. The association between the symptom
vaginal bulge and anatomical POP at the various visits was analyzed using
Fisher's exact test. RESULTS: Prevalence of vaginal bulge ranged between 16 and
23%. At 6 weeks postpartum the symptom was associated with anatomical POP;
otherwise, these two features were unrelated. CONCLUSIONS: The symptom vaginal
bulge was barely associated with anatomical POP, and cannot identify anatomical
POP in pregnancy or postpartum.
PMID- 28698893
TI - Cytotoxicity against tumor cell lines and anti-inflammatory properties of
chitinases from Calotropis procera latex.
AB - The role of chitinases from the latex of medicinal shrub Calotropis procera on
viability of tumor cell lines and inflammation was investigated. Soluble latex
proteins were fractionated in a CM Sepharose Fast-Flow Column and the major peak
(LPp1) subjected to ion exchange chromatography using a Mono-Q column coupled to
an FPLC system. In a first series of experiments, immortalized macrophages were
cultured with LPp1 for 24 h. Then, cytotoxicity of chitinase isoforms (LPp1-P1 to
P6) was evaluated against HCT-116 (colon carcinoma), OVCAR-8 (ovarian carcinoma),
and SF-295 (glioblastoma) tumor cell lines in 96-well plates. Cytotoxic
chitinases had its anti-inflammatory potential assessed through the mouse
peritonitis model. We have shown that LPp1 was not toxic to macrophages at
dosages lower than 125 MUg/mL but induced high messenger RNA expression of IL-6,
IL1-beta, TNF-alpha, and iNOs. On the other hand, chitinase isoform LPp1-P4
retained all LPp1 cytotoxic activities against the tumor cell lines with IC50
ranging from 1.2 to 2.9 MUg/mL. The intravenous administration of LPp1-P4 to
mouse impaired neutrophil infiltration into the peritoneal cavity induced by
carrageenan. Although the contents of pro-inflammatory cytokines IL-6, TNF-alpha,
and IL1-beta were high in the bloodstreams, such effect was reverted by
administration of iNOs inhibitors NG-nitro-L-arginine methyl ester and
aminoguanidine. We conclude that chitinase isoform LPp1-P4 was highly cytotoxic
to tumor cell lines and capable to reduce inflammation by an iNOs-derived NO
mechanism.
PMID- 28698894
TI - Wischnewsky-like spots in fatal cases of canine hypothermia.
AB - Two dogs with a history of being found dead within environments exposed to
extremely cold weather were examined postmortem. In both cases, brown to red to
black, round to irregularly shaped foci ranging from 0.5-15 mm in diameter were
identified within the mucosa of the stomach. These foci are grossly and
microscopically consistent with Wischnewsky spots that are reported in humans.
These spots in the mucosa of the stomach are considered important findings in
cases of hypothermia-related deaths in humans and are for the first time reported
in the dog.
PMID- 28698895
TI - Using anatomical landmark to avoid phrenic nerve injury during balloon-based
procedures in atrial fibrillation patients.
AB - PURPOSE: Atrial fibrillation (AF) is an arrhythmia which affects as many as 2.7
million Americans. AF should be treated, because it can lead to a four-to
fivefold increased risk of experiencing a stroke. The American College of
Cardiology/American Heart Association guidelines for the treatment of drug
refractory and symptomatic paroxysmal AF denote catheter ablation as the standard
of care. The newest ablation treatment, cryoballoon, uses a cold balloon tip. The
biggest risk factor associated with the cryoballoon ablation is phrenic nerve
injury (PNI). The purpose of this study is to measure relevant distances from
specific landmarks to the right phrenic nerve (RPN) to create a safe zone for
physicians. METHODS: Using 30 cadaveric specimens, we measured laterally from the
right superior pulmonary vein orifice (RSPV) to the RPN at the level of the sixth
thoracic vertebra and laterally from the lateral border of the sixth thoracic
vertebral body (T6) to the RPN. The depth and width of the left atrium (LA) were
also measured to establish a cross-sectional area of the LA. The cross-sectional
area of the LA was then correlated with the averaged measurements to see if the
area of the LA could be a predictor of the location of the RPN. RESULTS: The
average distance from the RPN-RSPV was 9.6 mm (range 4.3-18.8 mm). The average
RPN-T6 distance was 30.6 mm (range 13.7-49.9 mm). There was a non-significant
trend that suggests as the size of the LA increases, the measured distances also
increased. CONCLUSION: Using the lateral border of the sixth thoracic vertebra as
a landmark, which can be viewed under fluoroscopy during the procedure,
physicians can triangulate the distance to the RSPV and determine the approximate
position of the RPN. Furthermore, physicians can perform a preoperative
echocardiogram to determine the size of the LA to assist in determining the
position of the RPN with the hopes of avoiding injury to the RPN.
PMID- 28698896
TI - The role of TSPO PET in assessing neuroinflammation.
PMID- 28698897
TI - Factors associated with good self-rated health in European adolescents: a
population-based cross-sectional study.
AB - OBJECTIVES: The aim of the present study was to investigate self-reported health
status and associated factors. METHODS: In this cross-sectional study, the
participants were 6501 adolescents (52% females) aged 14-19 years from three
European countries: Croatia, Lithuania and Serbia. Self-rated health was assessed
by using one item question: "How would you perceive your health?" The answers
were arranged along a 5-point Likert-type scale: (1) very poor, (2) poor, (3)
fair, (4) good and (5) excellent. The outcome was binarized as "good" (fair, good
and excellent) and "poor" health (very poor and poor). Potential factors
associated with self-rated health included demographic (age, gender,
socioeconomic status and body-mass index), social (social capital) and lifestyle
(physical activity and psychological distress) variables. RESULTS: In both
univariate and multivariate models, being older, being a boy, having higher level
of family, neighbourhood and school social capital, participating in moderate-to
vigorous physical activity more frequently and having low psychological distress
were associated with good self-rated health. CONCLUSIONS: Our findings suggest
strong associations between social and lifestyle factors and self-rated health.
Other explanatory variables will require future research.
PMID- 28698898
TI - [Myasthenia gravis should be considered in cases of Parkinson's disease and
progressive dysphagia].
AB - We report on four consecutive patients with Parkinson's disease, in whom anti
acetylcholine receptor (AChR) antibody positive bulbar myasthenia gravis (MG)
turned out to be responsible for progressive dysphagia.
PMID- 28698899
TI - Methodical endoscopic repair of congenital indirect inguinoscrotal hernia in
adult male patients with completely patent processus vaginalis.
AB - PURPOSE: Indirect inguinal hernia related to the presence of a patent processus
vaginalis (PPV) in adult is estimated to be around 15%. Most surgeons would favor
a standard anterior hernioplasty to minimize the potential risk of damaging the
spermatic cord structures that are always intimately fused to the congenital
peritoneal sac. This also means overlooking the potential benefit of alternative
posterior techniques such as endoscopic totally extraperitoneal (TEP) repair that
is known to offer faster recovery with reduced risk of developing chronic groin
pain. The aim of this study was to evaluate the safety of TEP approach for repair
of adult inguinoscrotal hernias associated with completely PPV and to compare
those results with a corresponding group of male patients undergoing an identical
procedure, but with no demonstrated PPV. METHODS: This is a prospective study of
consecutive male patients diagnosed with inguinal hernia during a 10-year period
and eligible for endoscopic TEP repair. Every recognized completely PPV were
systematically divided taking care not to damage the attached cord structures and
the proximal end closed with a pre-tied Endoloop of PDS. In both groups, all
meshes were secured with fibrin sealant only. Patients were reviewed in clinic 2
and 6 weeks after the operation. Further follow-up was scheduled if deemed
necessary. The primary post-operative outcome parameter was spermatic cord
injury; secondary outcome parameters included groin pain, surgical complications,
and recurrence. RESULTS: Nine hundred and thirty-nine hernia repairs were
prospectively recorded during this period. All procedures were carried out
endoscopically. A total of 41 patients with a median age of 27 years presented
with 43 inguinoscrotal hernias (two bilateral) related to the presence of a
congenital completely PPV. 72% of them were right-sided. No injury to the cord
structures was recorded and only one complication (2.4%) occurred at 1 week post
operatively that was unrelated to the PPV. There was no report of chronic groin
or testicular pain, symptomatic seroma formation, or hernia recurrence. By
comparison, out of the 608 patients representing the no PPV group, there were 35
complications out of 33 patients (5.4%), one of those requiring subsequent
laparoscopic revision. Only one early post-operative recurrence was recorded in
this group (0.15%). CONCLUSIONS: In the presence of a completely PPV, the
recognized benefit of a posterior approach, such as endoscopic TEP inguinal
hernia repair, outweighs the theoretical risk of damaging the spermatic cord
structures when dissecting and dividing the congenital hernia sac. This technique
should be the preferred option among expert laparoscopic surgeons.
PMID- 28698900
TI - Simulation-based mastery learning for endoscopy using the endoscopy training
system: a strategy to improve endoscopic skills and prepare for the fundamentals
of endoscopic surgery (FES) manual skills exam.
AB - INTRODUCTION: The fundamentals of endoscopic surgery (FES) program has
considerable validity evidence for its use in measuring the knowledge, skills,
and abilities required for competency in endoscopy. Beginning in 2018, the
American Board of Surgery will require all candidates to have taken and passed
the written and performance exams in the FES program. Recent work has shown that
the current ACGME/ABS required case volume may not be enough to ensure trainees
pass the FES skills exam. The aim of this study was to investigate the
feasibility of a simulation-based mastery-learning curriculum delivered on a
novel physical simulation platform to prepare trainees to pass the FES manual
skills exam. METHODS: The newly developed endoscopy training system (ETS) was
used as the training platform. Seventeen PGY 1 (10) and PGY 2 (7) general surgery
residents completed a pre-training assessment consisting of all 5 FES tasks on
the GI Mentor II. Subjects then trained to previously determined expert
performance benchmarks on each of 5 ETS tasks. Once training benchmarks were
reached for all tasks, a post-training assessment was performed with all 5 FES
tasks. RESULTS: Two subjects were lost to follow-up and never returned for
training or post-training assessment. One additional subject failed to complete
any portion of the curriculum, but did return for post-training assessment. The
group had minimal endoscopy experience (median 0, range 0-67) and minimal prior
simulation experience. Three trainees (17.6%) achieved a passing score on the pre
training FES assessment. Training consisted of an average of 48 +/- 26
repetitions on the ETS platform distributed over 5.1 +/- 2 training sessions.
Seventy-one percent achieved proficiency on all 5 ETS tasks. There was dramatic
improvement demonstrated on the mean post-training FES assessment when compared
to pre-training (74.0 +/- 8 vs. 50.4 +/- 16, p < 0.0001, effect size = 2.4). The
number of ETS tasks trained to proficiency correlated moderately with the score
on the post-training assessment (r = 0.57, p = 0.028). Fourteen (100%) subjects
who trained to proficiency on at least one ETS task passed the post-training FES
manual skills exam. CONCLUSIONS: This simulation-based mastery learning
curriculum using the ETS is feasible for training novices and allows for the
acquisition of the technical skills required to pass the FES manual skills exam.
This curriculum should be strongly considered by programs wishing to ensure that
trainees are prepared for the FES exam.
PMID- 28698901
TI - Circulating osteoprotegerin levels are elevated in rheumatoid arthritis: a
systematic review and meta-analysis.
AB - This study aimed to systemically review the evidence regarding the relationship
between the circulating blood osteoprotegerin (OPG) level and rheumatoid
arthritis (RA), as well as the potential influential factors. Research related to
plasma/serum OPG levels in RA patients and healthy controls were gathered using
PubMed, EMBASE, and The Cochrane Library database (up to Jan. 1, 2017). Pooled
standard mean difference (SMD) with 95% confidence interval (CI) was calculated
by fixed-effects or random-effect model analysis. Heterogeneity test was
performed by the Q statistic and quantified using I 2, and publication bias was
evaluated using a funnel plot and Egger's linear regression test. After searching
databases, 443 articles were obtained, and 11 studies with 710 RA patients and
561 controls were finally included. Meta-analysis revealed that, compared with
the control group, the OPG level was significantly higher in the RA group (P <
0.001), with the SMD of 1.02 and 95%CI (0.20, 1.84). Subgroup analyses showed
that race, disease duration, body mass index (BMI), and disease activity score
based on the assessment of 28 joints (DAS28) were positively associated with OPG
level in RA patients. Our meta-analysis revealed a significantly higher
circulating OPG level in RA patients, and it was influenced by race, disease
duration, BMI, and DAS28.
PMID- 28698902
TI - [Radiotherapy enhances the effect of PD-1 checkpoint inhibitors].
PMID- 28698903
TI - [Optimal fractionation regimen, and time between radiotherapy and operation in
rectal cancer : The multicenter, randomized Stockholm III trial].
PMID- 28698904
TI - [No evidence for radiation-induced tumors after intracranial radiosurgery].
PMID- 28698905
TI - Comparative transcriptional analysis of hop responses to infection with
Verticillium nonalfalfae.
AB - KEY MESSAGE: Dynamic transcriptome profiling revealed excessive, yet ineffective,
immune response to V. nonalfalfae infection in susceptible hop, global gene
downregulation in shoots of resistant hop and only a few infection-associated
genes in roots. Hop (Humulus lupulus L.) production is hampered by Verticillium
wilt, a disease predominantly caused by the soil-borne fungus Verticillium
nonalfalfae. Only a few hop cultivars exhibit resistance towards it and
mechanisms of this resistance have not been discovered. In this study, we
compared global transcriptional responses in roots and shoots of resistant and
susceptible hop plants infected by a lethal strain of V. nonalfalfae. Time-series
differential gene expression profiles between infected and mock inoculated plants
were determined and subjected to network-based analysis of functional enrichment.
In the resistant hop cultivar, a remarkably low number of genes were
differentially expressed in roots in response to V. nonalfalfae infection, while
the majority of differentially expressed genes were down-regulated in shoots. The
most significantly affected genes were related to cutin biosynthesis, cell wall
biogenesis, lateral root development and terpenoid biosynthesis. On the other
hand, susceptible hop exhibited a strong defence response in shoots and roots,
including increased expression of genes associated with plant responses, such as
innate immunity, wounding, jasmonic acid pathway and chitinase activity. Strong
induction of defence-associated genes in susceptible hop and a low number of
infection-responsive genes in the roots of resistant hop are consistent with
previous findings, confirming the pattern of excessive response of the
susceptible cultivar, which ultimately fails to protect the plant from V.
nonalfalfae. This research offers a multifaceted overview of transcriptional
responses of susceptible and resistant hop cultivars to V. nonalfalfae infection
and represents a valuable resource in the study of this plant-pathogen
interaction.
PMID- 28698906
TI - Comparative ultrastructure of fruit plastids in three genetically diverse
genotypes of apple (Malus * domestica Borkh.) during development.
AB - KEY MESSAGE: Comparative ultrastructural developmental time-course analysis has
identified discrete stages at which the fruit plastids undergo structural and
consequently functional transitions to facilitate subsequent development-guided
understanding of the complex plastid biology. Plastids are the defining organelle
for a plant cell and are critical for myriad metabolic functions. The role of
leaf plastid, chloroplast, is extensively documented; however, fruit plastids
chromoplasts-are poorly understood, especially in the context of the diverse
metabolic processes operating in these diverse plant organs. Recently, in a
comparative study of the predicted plastid-targeted proteomes across seven plant
species, we reported that each plant species is predicted to harbor a unique set
of plastid-targeted proteins. However, the temporal and developmental context of
these processes remains unknown. In this study, an ultrastructural analysis
approach was used to characterize fruit plastids in the epidermal and
collenchymal cell layers at 11 developmental timepoints in three genotypes of
apple (Malus * domestica Borkh.): chlorophyll-predominant 'Granny Smith',
carotenoid-predominant 'Golden Delicious', and anthocyanin-predominant 'Top Red
Delicious'. Plastids transitioned from a proplastid-like plastid to a chromoplast
like plastid in epidermis cells, while in the collenchyma cells, they
transitioned from a chloroplast-like plastid to a chloro-chromo-amyloplast
plastid. Plastids in the collenchyma cells of the three genotypes demonstrated a
diverse array of structures and features. This study enabled the identification
of discrete developmental stages during which specific functions are most likely
being performed by the plastids as indicated by accumulation of plastoglobuli,
starch granules, and other sub-organeller structures. Information regarding the
metabolically active developmental stages is expected to facilitate biologically
relevant omics studies to unravel the complex biochemistry of plastids in
perennial non-model systems.
PMID- 28698907
TI - Virtual Issue #1: Oil Spill Research in the Bulletin of Environmental
Contamination and Toxicology.
PMID- 28698908
TI - [Adult autopsies during the past decade in Germany : Data from two university
hospitals].
AB - BACKGROUND: The clinical autopsy is the ultimate medical service for a patient
and plays a crucial role in the education of physicians and other medical
personnel, as well as in the context of quality control. Nevertheless, the number
of autopsies is constantly decreasing. Numerous factors, such as the personal
attitude of relatives and also clarification of relatives, as well as the
increasing application of imaging methods while the patient is still alive, play
a central role in this decline. OBJECTIVE: This study aimed to demonstrate the
development of autopsy services over the past decade in two university hospitals
in Germany and therefore to underline the importance of this investigation
procedure in pathology. MATERIAL AND METHODS: Autopsy reports between the years
2005 and 2014 from 2 university institutes of pathology were analyzed regarding a
diverse dataset, including age and sex of the deceased as well as the clinical
and pathological causes of death. RESULTS: The data showed that the number of
autopsies has continuously decreased over the past decade; however, the
distribution of characteristics of the deceased remained relatively stable. In
this cohort the clinically assumed cause of death differed from the pathological
cause of death in 6% of the autopsies. Frequently occurring discrepant diagnoses
were cardiac tamponade, aortic dissection and endocarditis/myocarditis.
DISCUSSION: Our results show that, despite significant improvements in imaging
methods, findings do not yield more accurate results than does autopsy. This
underscores once again the need to encourage the performance of this final
medical act on patients.
PMID- 28698909
TI - The cisternal segment of the anterior choroidal artery: an anatomical study using
magnetic resonance imaging.
AB - PURPOSE: The topography of the anterior choroidal artery (AChA) has infrequently
been delineated on neuroimages. The present study aimed to explore the cisternal
segment of the AChA using magnetic resonance imaging. METHODS: A total of 50
sides of the AChA obtained from 25 patients were included in this study. A
constructive interference in steady-state (CISS) sequence was performed in thin
sliced axial sections. Furthermore, the cisternal AChA and relevant neurovascular
structures were observed through cadaveric dissections in two heads. RESULTS: In
the cadaveric dissections, all the AChAs were exposed only in the proximal part
even after extensive arachnoid dissections and cerebral retraction. In the
examinations with the CISS sequence, the original site of the AChA was identified
on the right side in 88% and on the left side in 96%. In 70% of the 50 sides, the
AChA arose from the posterolateral wall of the internal carotid artery, distally
to that of the posterior communicating artery. The cisternal course of the AChA
was delineated on the right side in 96% and on the left side in 100%; it crossed
over the optic tract in variable manners with the middle third as the most
frequent site found in 60% of the sides. CONCLUSIONS: The cisternal AChA shows a
morphological variability. The CISS sequence is useful for delineating the
cisternal AChA.
PMID- 28698910
TI - Erratum to: Structural characterization of an all-aminosugar-containing capsular
polysaccharide from Colwellia psychrerythraea 34H.
PMID- 28698911
TI - Exploration of Up-regulated Key Proteins in Pseudomonas Aeruginosa for High
efficiency Petroleum Degradation by Proteomic Analysis.
AB - In this work, proteomic analysis was used to identify the up-regulated key
proteins of Pseudomonas aeruginosa (P6), a bacteria used in petroleum
degradation, responsible for its high efficiency in degrading crude oil.
Seventeen proteins were identified as up-regulated proteins by proteomic analysis
and classified by bioinformatics analysis. The results indicated that most of the
up-regulated proteins were responsible for P. aeruginosa (P6) survival under
harsh environmental conditions and utilization crude oil as carbon source in a
better way. The physiological processes, chemotaxis to carbon sources, terminal
oxidation of carbons, carbon source uptake and nutrients transport, were
associated with the up-regulated proteins in the study. The findings revealed the
most influential proteins and set a clear direction for future research.
PMID- 28698912
TI - Spirosoma areae sp. nov., Isolated from Soil.
AB - A yellow-colored Gram-negative strain, Arct 1-12T, was isolated from a soil
sample collected in Seoul Women's University, South Korea, and grown on R2A agar
at 25 degrees C. Growth of strain Arct 1-12T was observed at a temperature range
of 15-30 degrees C (optimal 25 degrees C), but not at 4 or 42 degrees C. The
strain tolerated up to 1% NaCl (w/v) and displayed optimal growth in the absence
of NaCl. Growth occurred at pH 6.0-9.0 (optimally at pH 7). According to the 16S
rRNA gene sequence, the strain is moderately related to Spirosoma spitsbergense
DSM 19989T (93.54%), S. endophyticum EX36T (93.25%), S. linguale LMG 10896T
(92%), S. luteum DSM 19990T (93.16%), S. panaciterrae DSM 21099T (91.09%), S.
oryzae RHs22T (90.37%), and S. rigui WPCB118T (91.54%). Chemotaxonomic analyses
revealed that strain Arct 1-12T possesses MK-7 as the predominant menaquinone, a
polar lipid profile consisting of phosphatidylethanolamine, an unknown
aminolipid, an unknown aminophospholipid, and an unknown lipid, and iso-C15:0,
C16:1 omega5c and Summed Feature 3 (C16:1 omega6c and/or C16:1 omega7c) as the
major fatty acids. The DNA G+C content is 52.3 mol %. Based on polyphasic
evidence, strain Arct 1-12T (=JCM 31025 T = KCTC 42814T) is classified as the
type strain of a novel Spirosoma species for which the name Spirosoma areae sp.
nov. is proposed.
PMID- 28698913
TI - Antibacterial and Antioxidant Constituents of Extracts of Endophytic Fungi
Isolated from Ocimum basilicum var. thyrsiflora Leaves.
AB - Fourteen fungal endophytes were isolated from the Ocimum basilicum var.
thyrsiflora leaves collected from Northern Thailand. Eight genera were identified
including Aspergillus, Ascochyta, Nigrospora, Blastomyces, Colletotrichum,
Exidia, Clitopilus, and Nomuraea. The antibacterial activity of crude extracts
from all endophytic fungi was tested against nine human bacterial pathogens:
Staphylococcus aureus, Staphylococcus epidermidis, Bacillus subtilis, Bacillus
cereus, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Vibrio
cholerae, and Vibrio parahaemolyticus. All crude extracts showed some degree of
antibacterial activity, but the crude extract from Nigrospora MFLUCC16-0605
exhibited broad spectrum activity with MIC values ranging from 7.81 to 250 ug/mL.
The antioxidant activity of all crude extracts was also investigated by DPPH
radical scavenging assay. Crude extract from MFLUCC16-0605 had high antioxidant
activity (IC50 value of 15.36 MUg/mL) comparable to the trolox and gallic acid
standards showing IC50 values of 2.56 and 12.89 MUg/mL, respectively. The
chemical composition of the crude extract from MFLUCC16-0605 was determined using
GC-MS. Sixty-two compounds were identified representing 92.09% of crude extract
with six major components including 5E,9E-farnesyl acetone, columellarin,
totarene, laurenan-2-one, and 8S,13-cedranediol. PCR amplification and sequencing
of the barcoding region identified MFLUCC16-0605 as belonging to Nigrospora
genus. The notable activities of MFLUCC16-0605 indicate that the endophyte is a
potent natural resource and its use as an antibacterial/antioxidant agent should
be further explored.
PMID- 28698914
TI - Multiple Brain Abscesses Caused by Trichosporon inkin in a Patient with X-Linked
Chronic Granulomatous Disease (CGD) Successfully Treated with Antifungal Therapy.
PMID- 28698915
TI - Surgical treatment of stage II posterior tibialis tendon dysfunction: ten-year
clinical and radiographic results.
AB - INTRODUCTION: Grade II chronic tibialis posterior tendon dysfunction (PTTD) poses
a reconstructive challenge to the orthopaedic surgeon. Aim of this retrospective
study is to report the clinical and radiographical results of a case series of 63
patients (102 ft) affected by grade II PTTD who underwent tailored surgical
treatment at 10-year mean follow-up. MATERIALS AND METHODS: Sixty-three patients
(102 ft) were available for clinical and radiological evaluation and were
retrospectively reviewed at a mean follow-up of 125.1 +/- 14.9 months. Tibialis
posterior (PTT) treatment was based on the pathological anatomy of the
degenerated tendon. PTT repair was performed in 53 cases. Flexor digitorum longus
transfer was performed in the remaining 49. Associated procedures were
represented by medial displacement calcaneal osteotomy (MDCO) and lateral column
lengthening (LCL) depending on the main clinical feature of the foot (hindfoot
valgus and forefoot abduction, respectively). Patients' evaluation included AOFAS
score and radiographic examination with measure of lateral talus-first metatarsal
angle (LTFMA) and talo-navicular coverage angle (TNCA). RESULTS WE OBSERVED FOUR
FAILURES: AOFAS hindfoot score was 89 +/- 10 points at final follow-up. Eighty
six per cent of the patients declared to be satisfied or satisfied with minor
reservations. An overall statistical significant decrease was observed in both
LTFMA and TNCA values. A better TNCA correction was observed in case of
associated LCL with respect to MDCO. DISCUSSION: Tailored PTT treatment
associated with MDCO or LCL seems provide long-term pain relief and satisfactory
function in the treatment of stage II posterior tibial tendon dysfunction.
PMID- 28698916
TI - Maternal supplementation with small-quantity lipid-based nutrient supplements
during pregnancy and lactation does not reduce depressive symptoms at 6 months
postpartum in Ghanaian women: a randomized controlled trial.
AB - We examined the impact on depression at 6 months postpartum of maternal
supplementation with small-quantity lipid-based nutrient supplement (SQ-LNS)
compared to supplementation with iron and folic acid (IFA) or multiple
micronutrients (MMN). In this partially double-blinded randomized controlled
trial, pregnant women <=20 weeks gestation (n = 1320) were recruited from
antenatal clinics and randomly assigned to receive either (1) SQ-LNS during
pregnancy and for 6 months postpartum, or (2) IFA during pregnancy only, or (3)
MMN during pregnancy and for 6 months postpartum. Maternal depressive symptoms
were measured at 6 months postpartum using the Edinburgh Postnatal Depression
Scale (EPDS). Women who scored 12 or more on the EPDS were considered to show
symptoms of depression. One thousand one hundred fifty-one women were included in
this analysis (LNS = 382, IFA = 387 and MMN = 382). Characteristics of the three
groups were similar at baseline, and there were no significant differences
between women who were included in the analysis (n = 1151) and those who were not
(n = 169). At 6 months postpartum, 13% of the women overall showed symptoms of
depression, and this did not differ by group (LNS = 13.1%, IFA = 11.2% and MMN =
14.7%. P = 0.36). The median (25, 75 percentile) EPDS score did not differ by
group (LNS 4.0 (1.0, 8.0), IFA 4.0 (1.0, 8.0), MMN 5.0 (2.0, 9.0), P transformed
= 0.13). Adjustment for covariates did not alter these findings. Maternal
supplementation with SQ-LNS compared to MMN or IFA did not affect postnatal
depressive symptoms in this sample of Ghanaian women.
PMID- 28698917
TI - Erratum to: Financial strain and birth weight: the mediating role of
psychological distress.
PMID- 28698918
TI - Micropleura huchzermeyeri n. sp. (Camallanida: Dracunculoidea: Micropleuridae)
from the Nile crocodile, Crocodylus niloticus Laurenti (Reptilia: Crocodylidae),
in South Africa.
AB - Micropleura huchzermeyeri n. sp. (Camallanida: Dracunculoidea: Micropleuridae) is
described from the peritoneal cavity of Crocodylus niloticus Laurenti (Reptilia:
Crocodylidae), based on a detailed study of its morphology using light and
scanning electron microscopy. The new species is compared with its congeners, M.
australiensis Moravec, Kay & Hobbs, 2004, M. vazi Travassos, 1933 and M. vivipara
von Linstow, 1906 from crocodilians, and with M. indica Khera, 1951 from
chelonian hosts. It can be distinguished from these by the length of its
spicules, which are longer than in all described species and a combination of
characters, including the presence of prominent lateral caudal papillae on the
level of the cloaca in males, the presence of conspicuous phasmids on the female
tail, the pre-equatorial position of the vulva and the length of the first-stage
larvae. Micropleura huchzermeyeri n. sp. is further characterised by having 14
cephalic papillae in both sexes and ten pairs of caudal papillae in males. This
is the first report of a representative of the genus Micropleura von Linstow,
1906 from a crocodilian in the Afrotropical region. Micropleura helicospicula Dey
Sarkar, 2003 is considered a species incertae sedis.
PMID- 28698919
TI - Unperturbed hydrocarbon chains and liquid phase bilayer lipid chains: a computer
simulation study.
AB - In this work, the properties of saturated and unsaturated fatty acid acyl chains
16:0, 18:0, 18:1(n-9)cis, 18:2(n-6)cis, 18:3(n-3)cis, 18:4(n-3)cis, 18:5(n-3)cis,
20:4(n-6)cis, 20:5(n-3)cis and 22:6(n-3)cis in a bilayer liquid crystalline state
and similar hydrocarbon chains (with CH[Formula: see text] terminal groups
instead of C=O groups) in the unperturbed state characterised by a lack of long
range interaction were investigated. The unperturbed hydrocarbon chains were
modelled by Monte Carlo simulations at temperature [Formula: see text] K; sixteen
fully hydrated homogeneous liquid crystalline phosphatidylcholine bilayers
containing these chains were studied by molecular dynamics simulations at the
same temperature. To eliminate effects of the simulation parameters, the
molecular dynamics and Monte Carlo simulations were carried out using the same
structural data and force field coefficients. From these computer simulations,
the average distances between terminal carbon atoms of the chains (end-to-end
distances) were calculated and compared. The trends in the end-to-end distances
obtained for the unperturbed chains were found to be qualitatively similar to
those obtained for the same lipid chains in the bilayers. So, for understanding
of a number of processes in biological membranes (e.g., changes in fatty acid
composition caused by environmental changes such as temperature and pressure), it
is possible to use, at least as a first approximation, the relationships between
the structure and properties for unperturbed or isolated hydrocarbon chains.
PMID- 28698920
TI - Prevention and reversal of social stress-escalated cocaine self-administration in
mice by intra-VTA CRFR1 antagonism.
AB - BACKGROUND: A history of brief intermittent social defeat stress can escalate
cocaine self-administration and induce long-term adaptations in the mesolimbic
dopamine system. Extra-hypothalamic corticotrophin releasing factor (CRF) has
been shown to be closely associated with stress-induced escalation of drug use.
How repeated stress modulates CRF release in the ventral tegmental area (VTA) and
the roles of CRF receptors during different phases of stress-induced cocaine self
administration remain to be defined. OBJECTIVE: The current study examines the
roles of CRF and CRF receptor 1 (CRFR1) in escalated intravenous cocaine self
administration after exposure to social defeat stress in mice. METHODS AND
RESULTS: First, CRFR1 antagonist (CP 376,395, 15 mg/kg, i.p.) given 30 min prior
to each social defeat episode prevented later escalated cocaine self
administration. When CP 376,395 (5 and 15 mg/kg, i.p.) was administered 10 days
after the last episode of social stress, the escalation of cocaine intake was
dose-dependently reversed. Moreover, socially defeated mice showed increased CRF
release in the VTA compared to controls. To further explore the role of CRFR1, CP
376,395 (0.5 and 1 MUg/0.2 MUl) was infused directly into the VTA before the
cocaine self-administration session. Intra-VTA antagonism of CRFR1 was sufficient
to reverse social defeat stress-escalated cocaine self-administration.
CONCLUSION: These findings suggest that CRF and CRFR1 exert multiple roles in the
response to social stress that are relevant to escalated cocaine self
administration.
PMID- 28698921
TI - Serum galectin-3, but not galectin-1, levels are elevated in schizophrenia:
implications for the role of inflammation.
AB - BACKGROUND: Previous studies have reported that galectin-3 is involved in
inflammatory processes in the central nervous system and that neuroinflammation
may play a role in the pathogenesis of schizophrenia. However, the link between
schizophrenia and various galectins is unclear. OBJECTIVE: The objective of the
present study is to determine whether galectin, a well-known lectin protein that
binds to MU-galactoside, is associated with chronic schizophrenia. METHODS:
Thirty-six patients with schizophrenia and 36 healthy controls participated in
this study. Schizophrenia symptoms were assessed using the Brief Psychiatry
Rating Scale (BPRS). Serum galectin-1 and galectin-3 levels were evaluated using
ELISA and compared between the participant groups. Correlation analyses were also
performed to examine the relationship between BPRS scores and each galectin
level. RESULTS: Serum galectin-3 levels were significantly higher in patients
with schizophrenia than they were in controls (p = 0.009, d = 0.640); however,
serum galectin-1 levels were not significantly different between the groups (p =
0.513). No significant correlation was identified between serum galectin-3 level
and the total BPRS score; however, a significant positive correlation was found
between the serum galectin-3 level and the positive symptom score of the BPRS
(rho = 0.355; p = 0.033). Additionally, a significant negative correlation was
identified between serum galectin-3 levels and the negative symptom score of the
BPRS (rho = -0.387; p = 0.020). CONCLUSIONS: Given the high serum levels of
galectin-3 found in patients with schizophrenia compared with that in controls,
these findings may support the inflammation hypothesis of schizophrenia.
PMID- 28698922
TI - Characterization of methyl parathion degradation by a Burkholderia zhejiangensis
strain, CEIB S4-3, isolated from agricultural soils.
AB - Through the use of an enrichment technique, we isolated from the agricultural
soils of Morelos in central Mexico a strain of Burkholderia zhejiangensis
identified as CEIB S4-3, it's could use the pesticide methyl parathion (MP) as
the only source of carbon and degrade completely p-nitrophenol (PNP). For more
efficient MP and PNP degradation by the CEIB S4-3 strain, the absence of an extra
carbon source, a large inoculum and an MP concentration up to 50 mg/l are
required. Sequence and annotation analysis of the draft genome, showed presence
of mpd functional gene, which was expressed and its activity on the MP was
confirmed. Additionally, the genes coding for enzymes in the benzoquinone pathway
(conducted by Gram-negative bacteria) and the benzenotriol pathway (conducted by
Gram-positive bacteria) were found, which was corroborated by identification of
intermediary metabolites by HPLC. Thus, we propose that B. zhejiangensis CEIB S4
3 uses both degradation pathways.
PMID- 28698923
TI - Sequence symmetry analysis in pharmacovigilance and pharmacoepidemiologic
studies.
AB - Sequence symmetry analysis (SSA) is a method for detecting adverse drug events by
utilizing computerized claims data. The method has been increasingly used to
investigate safety concerns of medications and as a pharmacovigilance tool to
identify unsuspected side effects. Validation studies have indicated that SSA has
moderate sensitivity and high specificity and has robust performance. In this
review we present the conceptual framework of SSA and discuss advantages and
potential pitfalls of the method in practice. SSA is based on analyzing the
sequences of medications; if one medication (drug B) is more often initiated
after another medication (drug A) than before, it may be an indication of an
adverse effect of drug A. The main advantage of the method is that it requires a
minimal dataset and is computationally efficient. By design, SSA controls time
constant confounders. However, the validity of SSA may be affected by time
varying confounders, as well as by time trends in the occurrence of exposure or
outcome events. Trend effects may be adjusted by modeling the expected sequence
ratio in the absence of a true association. There is a potential for false
positive or negative results and careful consideration should be given to
potential sources of bias when interpreting the results of SSA studies.
PMID- 28698924
TI - Development of a novel WOrk-Related Questionnaire for UPper extremity disorders
(WORQ-UP).
AB - PURPOSE: The aim of this study is to develop a patient-reported outcome measure
(PROM) that identifies work-related limitations among patients with upper
extremity musculoskeletal disorders in order to enhance work-directed care in
daily orthopaedic practice, and to assess its content validity. METHODS: The
questionnaire was developed following the evaluation of existing PROMs and
consensus within the research team. The content validity was assessed in three
steps: (1) one on one interviews with patients (n = 14) were held to discuss the
clarity and possible adaptation of items; (2) experts from the field
(physiotherapists, insurance physicians, occupational health physicians,
rehabilitation physicians and orthopaedic surgeons) were approached to
participate in an interview to discuss the clarity, relevance and missing items;
(3) patients (n = 12) were interviewed one on one to discuss the final version.
RESULTS: The first version of the WOrk-Related Questionnaire for UPper extremity
disorders (WORQ-UP) consisted of 18 items based on the criteria: exertion,
dexterity, handling tools & equipment, and mobility. According to patients (n =
14), 44% of the items were not easy enough to understand. Twenty-one experts [10
men, mean age 46 (SD = 8.5) and mean years of experience 16 (SD = 9.9)]
participated in the interviews and adaptations were made. The final version of
the WORQ-UP consisted of 17 items, all easy enough to understand according to
patients (n = 12). CONCLUSIONS: A PROM specific for work-related limitations in
patients with upper extremity musculoskeletal disorders was developed. According
to patients and experts, it has sufficient content validity. The WORQ-UP can be
used to assist in enhancing communication among healthcare workers to improve
work-directed care and to evaluate effects of treatment on limitations at work.
PMID- 28698925
TI - Prolonged perceived stress and saliva cortisol in a large cohort of Danish public
service employees: cross-sectional and longitudinal associations.
AB - PURPOSE: It is well known that acute stress can lead to a transient increase in
cortisol secretion, but the effects of prolonged stress on cortisol secretion are
uncertain. This study examines the cross-sectional and longitudinal associations
between prolonged perceived stress and salivary cortisol. METHODS: In 2007, 4467
Danish public service employees participated in a study of stress and mental
health, and 3217 participated in a follow-up in 2009. Perceived stress during the
past 4 weeks was assessed by Cohen's four item perceived stress scale.
Participants were asked to collect saliva 30 min after awakening and at
approximately 20:00 in the evening. The cortisol dependence on perceived stress
was examined in regression analyses adjusted for effects of potential
confounders. We adjusted for a large variation in saliva sampling times by
modelling the time trajectory of cortisol concentrations in the morning and in
the evening and examined if they were influenced by perceived stress. RESULTS:
Perceived stress had no statistically significant effects on the level or time
trajectory of morning or evening cortisol, neither cross-sectionally nor
longitudinally. The 1 month prevalence of frequently perceived stress was low,
approximately 2.5%. CONCLUSION: Our results did not support the hypothesis that
prolonged perceived stress is associated with the level or time trajectory of
morning or evening salivary cortisol.
PMID- 28698926
TI - Diagnosis of Dementia by Machine learning methods in Epidemiological studies: a
pilot exploratory study from south India.
AB - BACKGROUND: There are limited data on the use of artificial intelligence methods
for the diagnosis of dementia in epidemiological studies in low- and middle
income country (LMIC) settings. A culture and education fair battery of cognitive
tests was developed and validated for population based studies in low- and middle
income countries including India by the 10/66 Dementia Research Group. AIMS: We
explored the machine learning methods based on the 10/66 battery of cognitive
tests for the diagnosis of dementia based in a birth cohort study in South India.
METHODS: The data sets for 466 men and women for this study were obtained from
the on-going Mysore Studies of Natal effect of Health and Ageing (MYNAH), in
south India. The data sets included: demographics, performance on the 10/66
cognitive function tests, the 10/66 diagnosis of mental disorders and population
based normative data for the 10/66 battery of cognitive function tests. Diagnosis
of dementia from the rule based approach was compared against the 10/66 diagnosis
of dementia. We have applied machine learning techniques to identify minimal
number of the 10/66 cognitive function tests required for diagnosing dementia and
derived an algorithm to improve the accuracy of dementia diagnosis. RESULTS: Of
466 subjects, 27 had 10/66 diagnosis of dementia, 19 of whom were correctly
identified as having dementia by Jrip classification with 100% accuracy.
CONCLUSIONS: This pilot exploratory study indicates that machine learning methods
can help identify community dwelling older adults with 10/66 criterion diagnosis
of dementia with good accuracy in a LMIC setting such as India. This should
reduce the duration of the diagnostic assessment and make the process easier and
quicker for clinicians, patients and will be useful for 'case' ascertainment in
population based epidemiological studies.
PMID- 28698927
TI - Time trends in mental well-being: the polarisation of young people's
psychological distress.
AB - PURPOSE: Previous research on time trends of young people's mental health in
Britain has produced conflicting findings: evidence for deterioration in mental
health during the late 20th century followed by stability and slight improvement
during the early 21st century is contrasted with evidence showing continued
deterioration. The present study adds to the evidence base by assessing time
trends in means, variances, and both low and high psychological distress scores
covering a similar period. METHODS: GHQ-12 (Likert scale) was regressed on time
(adjusting for age) using a sample of young people aged 16-24 between 1991 and
2008 from the British Household Panel Study. Change in variance was assessed
using Levene's homogeneity of variance test across 9-year intervals. Polarisation
was assessed by a comparison of the prevalence of scores >=1 standard deviation
and >=1.5 standard deviations above and below the pooled mean. RESULTS: There was
a small but significant increase in mean GHQ-12 among young women (b 0.048; 95%
CI 0.016, 0.080) only. Variance increased significantly (p < 0.05) across 9-year
intervals in seven out of nine comparisons for women and in six out of nine
comparisons for men. There were significant increases in low (OR: 1.19; 95% CI
1.05, 1.35), high (OR: 1.27; 95% CI 1.13, 1.42), and very high scores (OR: 1.42;
95% CI 1.23, 1.64) for young women, and increases in low (OR: 1.39; 95% CI 1.21,
1.59) and very low (OR: 1.53; 95% CI 1.21, 1.92) scores for young men.
CONCLUSIONS: The evidence suggests a polarisation of the psychological distress
of young women in Britain between 1991 and 2008.
PMID- 28698928
TI - Severe musculoskeletal time-loss injuries and symptoms of common mental disorders
in professional soccer: a longitudinal analysis of 12-month follow-up data.
AB - PURPOSE: Psychological factors have shown to be predictors of injury in
professional football. However, it seems that this is a two-way relationship, as
severe musculoskeletal time-loss injuries have shown to be associated with the
onset of symptoms of common mental disorders (CMD). There is no longitudinal
study performed exploring this interaction between symptoms of CMD and injuries.
The purpose of this study was to explore the interaction between severe
musculoskeletal time-loss injuries and symptoms of CMD in professional football
players over a 12-month period. METHODS: Players were recruited by their national
players' unions in five European countries. Symptoms of CMD included in the study
were related to distress, anxiety/depression, sleep disturbance and adverse
alcohol use. RESULTS: A total of 384 professional football players were enrolled
in the study, of whom 262 (68%) completed the 12-month follow-up period. The mean
age of the participants at baseline was 27 +/- 5 years, and they had played
professional football for 8 +/- 5 years on average. Symptoms of CMD at baseline
were not associated with the onset of severe musculoskeletal time-loss injuries
during the follow-up period with relative risks (and 95% CI) ranging from 0.6
(0.3-1.0) to 1.0 (0.5-2.2). In contrast, severe musculoskeletal time-loss
injuries reported at baseline were associated with the onset of symptoms of CMD
during the follow-up period with relative risks ranging from 1.8 (0.8-3.7) to 6.9
(4.0-11.9). CONCLUSION: No relationship was found between symptoms of CMD and the
onset of severe musculoskeletal time-loss injuries. However, professional
football players who suffered from severe musculoskeletal time-loss injuries are
likely to develop subsequent symptoms of CMD. This study emphasizes the need for
an interdisciplinary medical approach, which not only focuses on the physical but
also on the mental health of professional football players. An early
identification of players at risk of symptoms of CMD, such as those suffering
from severe musculoskeletal injuries, creates the opportunity for an
interdisciplinary clinical medical team to treat the players timely and
adequately. LEVEL OF EVIDENCE: Prospective cohort study, Level II.
PMID- 28698929
TI - Favourable alignment outcomes with MRI-based patient-specific instruments in
total knee arthroplasty.
AB - PURPOSE: Patient-specific instruments (PSIs) are already in relatively common
use, and their post-operative radiographic results are equal to those for total
knee arthroplasty (TKA) with conventional instrumentation. PSI use requires a
preoperative MRI scan, CT scan, or a combination of MRI and a long-leg standing
radiograph. However, there is no consensus as to which of these modalities, MRI
or CT, is the preferred imaging modality when performing TKA with PSIs. METHODS:
This systematic literature review and meta-analysis studied the differences in
alignment outliers between CT- and MRI-based PSI for TKA. A search of the
Cochrane Database of Systematic Reviews, MEDLINE/PubMed and Embase was conducted,
without restriction on date of publication. Only level I evidence studies written
in English that included TKA with the use of MRI- and CT-based PSI were selected.
A meta-analysis was then performed of the rate of outliers in the biomechanical
axis and individual femoral and tibial component alignment. Where considerable
heterogeneity among studies was present or the data did not provide sufficient
information for performing the meta-analysis, a qualitative synthesis was
undertaken. RESULTS: Twelve randomized controlled trials, studying 841 knees,
were eligible for data extraction and meta-analysis. MRI-based PSI resulted in a
significantly lower proportion of coronal plane outliers with regard to the
lateral femoral component (OR 0.52, 95% CI 0.30-0.89, P = 0.02), without
significant heterogeneity (n.s.). There were no significant differences regarding
the biomechanical axis or frontal femoral and individual tibial component
alignment. CONCLUSION: This systematic review and meta-analysis demonstrate that
alignment with MRI-based PSI is at least as good as, if not better than, that
with CT-based PSI. To prevent for malalignment, MRI should be the imaging
modality of choice when performing TKA surgery with PSI. LEVEL OF EVIDENCE: I.
PMID- 28698930
TI - Proliposome Powders for the Generation of Liposomes: the Influence of
Carbohydrate Carrier and Separation Conditions on Crystallinity and Entrapment of
a Model Antiasthma Steroid.
AB - Formulation effects on the entrapment of beclometasone dipropionate (BDP) in
liposomes generated by hydration of proliposomes were studied, using the high
density dispersion medium deuterium oxide in comparison to deionized water (DW).
Proliposomes incorporating BDP (2 mol% of the lipid phase consisting of soya
phosphatidylcholine (SPC) and cholesterol; 1:1) were manufactured, using lactose
monohydrate (LMH), sorbitol or D-mannitol as carbohydrate carriers (1:5 w/w lipid
to carrier). Following hydration of proliposomes, separation of BDP-entrapped
liposomes from the unentrapped (free) BDP at an optimized centrifugation duration
of 90 min and a centrifugation force of 15,500g were identified. The dispersion
medium was found to have a major influence on separation of BDP-entrapped
liposomes from the unentrapped drug. Entrapment efficiency values were higher
than 95% as estimated when DW was used. By contrast, the entrapment efficiency
was 19.69 +/- 5.88, 28.78 +/- 4.69 and 34.84 +/- 3.62% upon using D2O as a
dispersion medium (for LMH-, sorbitol- and D-mannitol-based proliposomes,
respectively). The similarity in size of liposomes and BDP crystals was found to
be responsible for co-sedimentation of liposomes and free BDP crystals upon
centrifugation in DW, giving rise to the falsely high entrapment values
estimated. This was remedied by the use of D2O as confirmed by light microscopy,
nuclear magnetic resonance (1HNMR), X-ray diffraction (XRD) and entrapment
studies. This study showed that carrier type has a significant influence on the
entrapment of BDP in liposomes generated from proliposomes, and using D2O is
essential for accurate determination of steroid entrapment in the vesicles.
PMID- 28698931
TI - How to stay perfect: the role of memory and behavioural traits in an experienced
problem and a similar problem.
AB - When animals encounter a task they have solved previously, or the same problem
appears in a different apparatus, how does memory, alongside behavioural traits
such as persistence, selectivity and flexibility, enhance problem-solving
efficiency? We examined this question by first presenting grey squirrels with a
puzzle 22 months after their last experience of it (the recall task). Squirrels
were then given the same problem presented in a physically different apparatus
(the generalisation task) to test whether they would apply the previously learnt
tactics to solve the same problem but in a different apparatus. The mean latency
to success in the first trial of the recall task was significantly different from
the first exposure but not different from the last exposure of the original task,
showing retention of the task. A neophobia test in the generalisation task
suggested squirrels perceived the different apparatus as a different problem, but
they quickly came to apply the same effective tactics as before to solve the
task. Greater selectivity (the proportion of effective behaviours) and
flexibility (the rate of switching between tactics) both enhanced efficiency in
the recall task, but only selectivity enhanced efficiency in the generalisation
task. These results support the interaction between memory and behavioural traits
in problem-solving, in particular memory of task-specific tactics that could
enhance efficiency. Squirrels remembered and emitted task-effective tactics more
than ineffective tactics. As a result, they consistently changed from ineffective
to effective behaviours after failed attempts at problem-solving.
PMID- 28698932
TI - Small molecules for reprogramming and transdifferentiation.
AB - Pluripotency reprogramming and transdifferentiation induced by transcription
factors can generate induced pluripotent stem cells, adult stem cells or
specialized cells. However, the induction efficiency and the reintroduction of
exogenous genes limit their translation into clinical applications. Small
molecules that target signaling pathways, epigenetic modifications, or metabolic
processes can regulate cell development, cell fate, and function. In the recent
decade, small molecules have been widely used in reprogramming and
transdifferentiation fields, which can promote the induction efficiency, replace
exogenous genes, or even induce cell fate conversion alone. Small molecules are
expected as novel approaches to generate new cells from somatic cells in vitro
and in vivo. Here, we will discuss the recent progress, new insights, and future
challenges about the use of small molecules in cell fate conversion.
PMID- 28698934
TI - Combination of Wuringer's Horizontal Septum and Inferior Pedicle Techniques to
Increase Nipple-Areolar Complex Viability During Breast Reduction Surgery.
AB - BACKGROUND: Breast reduction techniques depend on the vascularity of the pedicle.
Preserving vascularity of the nipple-areolar complex (NAC) is mandatory for
reduction mammoplasties, as the NAC is the most important aesthetic and
functional unit of the breast. The inferior pedicle technique is the most common
method for breast reduction; however, pedicle length may increase after using
this technique and cause problems related to NAC viability in gigantomastic and
hypertrophic breasts. In this study, we present our technical approach to
preserve NAC viability by combining Wuringer's horizontal septum and inferior
pedicle techniques. METHODS: This study included 60 women (mean age 39.71 +/-
10.52 years) who underwent a breast reduction combining Wuringer's horizontal
septum and inferior pedicle procedures from April 2012 to January 2016. All
patients were marked preoperatively in a standing upright position using a
prefabricated Wise-pattern template. The base of the pedicle was marked at the
level of the inframammary ridge at a width of 8 cm. RESULTS: The patients were
followed up for a mean of 5.6 +/- 3.3 months. The resection weights of the right
and left sides were 1406 +/- 566 and 1340 +/- 563 g, respectively. Venous
insufficiency was encountered in five cases (8.3%) and caused partial NAC
necrosis in one case (1.6%). No cases of total NAC necrosis were encountered.
Fifteen breasts (12.5%) were described as gigantomastic (resection weight >2000
g). CONCLUSIONS: This combined method may promote safer and more satisfying
outcomes from inferior pedicle breast reduction. LEVEL OF EVIDENCE IV: This
journal requires that authors assign a level of evidence to each article. For a
full description of these Evidence-Based Medicine ratings, please refer to the
Table of Contents or the online Instructions to Authors www.springer.com/00266 .
PMID- 28698933
TI - Distinct effects on the dendritic arbor occur by microbead versus bath
administration of brain-derived neurotrophic factor.
AB - Proper communication among neurons depends on an appropriately formed dendritic
arbor, and thus, aberrant changes to the arbor are implicated in many
pathologies, ranging from cognitive disorders to neurodegenerative diseases. Due
to the importance of dendritic shape to neuronal network function, the morphology
of dendrites is tightly controlled and is influenced by both intrinsic and
extrinsic factors. In this work, we examine how brain-derived neurotrophic factor
(BDNF), one of the most well-studied extrinsic regulators of dendritic branching,
affects the arbor when it is applied locally via microbeads to cultures of
hippocampal neurons. We found that local application of BDNF increases both
proximal and distal branching in a time-dependent manner and that local BDNF
application attenuates pruning of dendrites that occurs with neuronal maturation.
Additionally, we examined whether cytosolic PSD-95 interactor (cypin), an
intrinsic regulator of dendritic branching, plays a role in these changes and
found strong evidence for the involvement of cypin in BDNF-promoted increases in
dendrites after 24 but not 48 h of application. This current study extends our
previous work in which we found that bath application of BDNF for 72 h, but not
shorter times, increases proximal dendrite branching and that this increase
occurs through transcriptional regulation of cypin. Moreover, this current work
illustrates how dendritic branching is regulated differently by the same growth
factor depending on its spatial localization, suggesting a novel pathway for
modulation of dendritic branching locally.
PMID- 28698935
TI - The Anterior SMAS Approach for Facelifting and for Buccal Fat Pad Removal.
AB - : Having performed numerous varieties of SMAS advancement including: plication,
resection, flap elevation with variable anterior deep dissection, the author has
developed a direct approach to the mobile anterior SMAS which allows correction
of midface descent, modest elevation of the modiolus, jawline correction, and,
where indicated, direct access for buccal fat pad resection. LEVEL OF EVIDENCE V:
This journal requires that authors assign a level of evidence to each article.
For a full description of these Evidence-Based Medicine ratings, please refer to
the Table of Contents or the online Instructions to Authors
www.springer.com/00266 .
PMID- 28698936
TI - Creation of an Aesthetic Male Nipple Areolar Complex in Female-to-Male
Transgender Chest Reconstruction.
AB - BACKGROUND: Female-to-male chest wall reconstruction is becoming more common, but
while there is a growing body of the literature describing technique and
algorithms, little detail is written on methods for creating a male appearing
nipple areolar complex (NAC) from a female NAC utilizing free nipple graft
techniques. Incorrect positioning of the NAC on the chest wall and suboptimal
shaping and sizing of the NAC are common pitfalls in male NAC creation. METHODS:
With this paper, we present techniques for nipple grafting to achieve improved
male appearing NACs, as well as a simple, reproducible method for appropriate
placement of the NAC relative to the borders of the pectoralis muscle. To
validate our technique, we performed photographic analysis of 64 NACs in 32
volunteers with BMI of 25 or less. RESULTS: The anatomic study determined the cis
male nipple to be positioned on average 2.5 cm medial to the lateral border of
the pectoralis muscle and 2.4 cm above the inferior pectoralis insertion. This
supports our surgical technique of positioning the NAC in relation to the
pectoralis borders rather than previously advocated anatomic landmarks. We also
present reliable techniques for creating a round or horizontally oval final NAC
shape as well as a composite grafting technique for cases of large papillae.
CONCLUSIONS: Our anatomic study supports placement of the male NAC relative to
lateral and inferior borders of the pectoralis muscle. Nipple grafting techniques
presented allow for a simple and reproducible method of creating an aesthetic
male NAC shape in female-to-male transgender chest reconstruction. LEVEL OF
EVIDENCE IV: This journal requires that authors assign a level of evidence to
each article. For a full description of these Evidence-Based Medicine ratings,
please refer to the Table of Contents or the online Instructions to Authors
www.springer.com/00266 .
PMID- 28698937
TI - Re: Correction of Rhytides, Peau d'Orange and Thin Dermis of the Face by
Neocollagenesis Using Novel Collagen Stimulating Slurry Protocol.
PMID- 28698938
TI - New Insights into the Anatomy of the Midface Musculature and its Implications on
the Nasolabial Fold (Discussion).
PMID- 28698939
TI - Systematic Review of Quality of Patient Information on Phalloplasty in the
Internet.
AB - BACKGROUND: An increasing number of patients, considering aesthetic surgery, use
Internet health information as their first source of information. However, the
quality of information available in the Internet on phalloplasty is currently
unknown. This study aimed to assess the quality of patient information on
phalloplasty available in the Internet. METHODS: The assessment of the Web sites
was based on the modified Ensuring Quality Information for Patients (EQIP)
instrument (36 items). Three hundred Web sites were identified by the most
popular Web search engines. RESULTS: Ninety Web sites were assessed after,
duplicates, irrelevant sources and Web sites in other languages rather than
English were excluded. Only 16 (18%) Web sites addressed >21 items, and scores
tended to be higher for Web sites developed by academic centers and the industry
than for Web sites developed by private practicing surgeons. The EQIP score
achieved by Web sites ranged between 4 and 29 of the total 36 points, with a
median value of 17.5 points (interquartile range, 13-21). The top 5 Web sites
with the highest scores were identified. CONCLUSIONS: The quality of patient
information on phalloplasty in the Internet is substandard, and the existing Web
sites present inadequate information. There is a dire need to improve the quality
of Internet phalloplasty resources for potential patients who might consider this
procedure. LEVEL OF EVIDENCE IV: This journal requires that authors assign a
level of evidence to each article. For a full description of these Evidence-Based
Medicine ratings, please refer to the Table of Contents or the online
Instructions to Authors www.springer.com/00266 .
PMID- 28698940
TI - Radiological outcome of postoperative sagittal balance on standing radiographs in
comparison to intraoperative radiographs in prone position when performing lumbar
spinal fusion.
AB - PURPOSE: Aim of this study is to show the outcome of postoperatively measured
lumbar lordosis in upright position in comparison to the intraoperatively
estimated lumbar lordosis in prone position, as the lumbar lordosis is one of the
most important factors for the clinical outcome after spinal fusion. MATERIALS
AND METHODS: Eighty-two patients, receiving lumbar fusion were included in this
retrospective study. Intraoperative radiographs were scanned. Then radiographs of
the whole spine pre- and postoperatively, as well as 1 year after surgery were
measured by a spine surgeon and a radiologist. The visible segment lordosis
angles were measured and compared (L2-S1, L3-S1, L4-S1, L5-S1). In addition, the
pelvic parameters pelvic incidence, pelvic tilt and sacral slope were measured
pre- and postoperatively. RESULTS: The intraobserver reliability was almost
perfect. The mean lordosis angle L4-S1 was 32.6 degrees +/- 7.8 degrees
intraoperatively and 29 degrees +/- 10.8 degrees postoperatively. A linear
correlation of these two measurements can be seen. In mean, the postoperative
lordosis is 4 degrees smaller than intraoperatively. This trend can also be seen
in the level L3-S1. In levels L2-S1 and L5-S1 the postoperative values were
slightly higher than intraoperatively, but without any significance. Also, 1 year
after surgery there were no significant changes in global lumbar lordosis.
CONCLUSION: Measuring lordosis angles intraoperatively resulted in almost the
same values as measurements in standing plane radiographs postoperatively,
despite prone position. These findings could especially be shown for the level L4
S1. The intraobserver reliability was almost perfect for both, intra- and
postoperative measurements. In conclusion, the intraoperative measurement of a
lumbar lordosis angle can perfectly predict the postoperative result.
PMID- 28698941
TI - Spine rod straightening as a possible cause for revision.
AB - In a previous study, the authors examined the elastic and short-term anelastic
springback of Ti6Al4V, CoCrMoC and A316L stainless steel spine rods to observe
how the rods mechanically respond in OR contouring. In that study rods were 200
mm long and only the movement at the tip was recorded. The implication of that
work was that rods will straighten in-vivo, however, in order for the mechanism
of straightening to be determined, the movement of individual bends over time
must first be elucidated. Spine rods used were, commercially pure titanium (CP
Ti) a primarily alpha-phase; Ti-6Al-4V; alpha/beta-phase titanium alloy from two
different suppliers (denoted by, Ti-6Al-4V (L) and Ti-6Al-4V); beta-phase
titanium (TNTZ) and CoCrMoC. Following contouring the rods were aged
unconstrained, in normal atmosphere or simulated body fluid (SBF) in a CO2
incubator for up to 288 h. Elastic springback is significantly different between
alloys with different microstructures. Both types of Ti6Al4V rods, while meeting
the ASTM F136 industry standard, have significantly different properties, most
importantly yield strength, flexural modulus, and springback. Environment showed
no significant impact on anelasticity. The anelastic response of Ti6Al4V L
sample, which has relatively more beta phase than the Ti6Al4V sample, follows the
pure beta phase TNTZ in its extended time response. CoCrMoC and CP Ti have a very
reduced anelastic response compared to the other alloys. This potentially can
have unanticipated effects on the outcome of spine procedures, as the surgeon is
reliant on the rods having similar properties to achieve a desired outcome.
PMID- 28698942
TI - MRI of the scrotum: Recommendations of the ESUR Scrotal and Penile Imaging
Working Group.
AB - OBJECTIVES: The Scrotal and Penile Imaging Working Group (SPI-WG) appointed by
the board of the European Society of Urogenital Radiology (ESUR) has produced
recommendations for magnetic resonance imaging (MRI) of the scrotum. METHODS: The
SPI-WG searched for original and review articles published before September 2016
using the Pubmed and Medline databases. Keywords used were 'magnetic resonance
imaging', 'testis or testicle or testicular', 'scrotum', 'intratesticular',
'paratesticular', 'extratesticular' 'diffusion-weighted', 'dynamic MRI'.
Consensus was obtained among the members of the subcommittee. The expert panel
proposed recommendations using Oxford Centre for Evidence-Based Medicine 2011
Levels of Evidence. RESULTS: The recommended MRI protocol should include T1-, T2
weighted imaging, diffusion-weighted imaging and dynamic contrast-enhanced MRI.
Scrotal MRI can be clinically applied for lesion characterisation (primary),
including both intratesticular and paratesticular masses, differentiation between
germ-cell and non-germ-cell neoplasms (evolving), characterisation of the
histological type of testicular germ cell neoplasms (TGCNs, in selected cases),
local staging of TGCNs (primary), acute scrotum (in selected cases), trauma (in
selected cases) and undescended testes (primary). CONCLUSIONS: The ESUR SPI-WG
produced this consensus paper in which the existing literature on MRI of the
scrotum is reviewed. The recommendations for the optimal imaging technique and
clinical indications are presented. KEY POINTS: * This report presents
recommendations for magnetic resonance imaging (MRI) of the scrotum. * Imaging
acquisition protocols and clinical indications are provided. * MRI is becoming
established as a worthwhile second-line diagnostic tool for scrotal pathology.
PMID- 28698943
TI - Noninvasive electrical conductivity measurement by MRI: a test of its validity
and the electrical conductivity characteristics of glioma.
AB - OBJECTIVES: This study noninvasively examined the electrical conductivity (sigma)
characteristics of diffuse gliomas using MRI and tested its validity. METHODS:
MRI including a 3D steady-state free precession (3D SSFP) sequence was performed
on 30 glioma patients. The sigma maps were reconstructed from the phase images of
the 3D SSFP sequence. The sigma histogram metrics were extracted and compared
among the contrast-enhanced (CET) and noncontrast-enhanced tumour components
(NCET) and normal brain parenchyma (NP). Difference in tumour sigma histogram
metrics among tumour grades and correlation of sigma metrics with tumour grades
were tested. Validity of sigma measurement using this technique was tested by
correlating the mean tumour sigma values measured using MRI with those measured
ex vivo using a dielectric probe. RESULTS: Several sigma histogram metrics of CET
and NCET of diffuse gliomas were significantly higher than NP (Bonferroni
corrected p <= .045). The maximum sigma of NCET showed a moderate positive
correlation with tumour grade (r = .571, Bonferroni-corrected p = .018). The mean
tumour sigma measured using MRI showed a moderate positive correlation with the
sigma measured ex vivo (r = .518, p = .040). CONCLUSIONS: Tissue sigma can be
evaluated using MRI, incorporation of which may better characterise diffuse
gliomas. KEY POINTS: * This study tested the validity of noninvasive electrical
conductivity measurements by MRI. * This study also evaluated the electrical
conductivity characteristics of diffuse glioma. * Gliomas have higher electrical
conductivity values than the normal brain parenchyma. * Noninvasive electrical
conductivity measurement can be helpful for better characterisation of glioma.
PMID- 28698944
TI - PETRA, MSVAT-SPACE and SEMAC sequences for metal artefact reduction in dental MR
imaging.
AB - OBJECTIVES: Dental MRI is often impaired by artefacts due to metallic dental
materials. Several sequences were developed to reduce susceptibility artefacts.
Here, we evaluated a set of sequences for artefact reduction for dental MRI for
the first time. METHODS: Artefact volume, signal-to-noise ratio (SNR) and image
quality were assessed on a 3-T MRI for pointwise encoding time reduction with
radial acquisition (PETRA), multiple-slab acquisition with view angle tilting
gradient, based on a sampling perfection with application-optimised contrasts
using different flip angle evolution (SPACE) sequence (MSVAT-SPACE), slice
encoding for metal-artefact correction (SEMAC) and compared to a standard SPACE
and a standard turbo-spin-echo (TSE) sequence. Field-of-view and acquisition
times were chosen to enable in vivo application. Two implant-supported prostheses
were tested (porcelain fused to metal non-precious alloy and monolithic
zirconia). RESULTS: Smallest artefact was measured for TSE sequences with no
difference between the standard TSE and the SEMAC. MSVAT-SPACE reduced artefacts
about 56% compared to the standard SPACE. Effect of the PETRA was dependent on
sample used. Image quality and SNR were comparable for all sequences except
PETRA, which yielded poor results. CONCLUSION: There is no benefit in terms of
artefact reduction for SEMAC compared to standard TSE. Usage of MSVAT-SPACE is
advantageous since artefacts are reduced and higher resolution is achieved. KEY
POINTS: * SEMAC is not superior to TSE in terms of artefact reduction. * MSVAT
SPACE reduces susceptibility artefacts while maintaining comparable image
quality. * PETRA reduces susceptibility artefacts depending on material but
offers poor image quality.
PMID- 28698945
TI - Cardiorespiratory Fitness is Associated with Reduced Risk of Respiratory Diseases
in Middle-Aged Caucasian Men: A Long-Term Prospective Cohort Study.
AB - Cardiorespiratory fitness (CRF), an index of cardiac and respiratory functioning,
is strongly associated with a reduced risk of adverse health outcomes. We aimed
to assess the prospective association of CRF with the risk of respiratory
diseases (defined as chronic obstructive pulmonary disease, pneumonia, or
asthma). Cardiorespiratory fitness, as measured by maximal oxygen uptake, was
assessed in 1974 middle-aged men. During a median follow-up of 25.7 years, 382
hospital diagnosed respiratory diseases were recorded. Cardiorespiratory fitness
was linearly associated with risk of respiratory diseases. In analysis adjusted
for several established and potential risk factors, the hazard ratio (HR) (95%
CI) for respiratory diseases was 0.63 (0.45-0.88), when comparing extreme
quartiles of CRF levels. The corresponding multivariate adjusted HR (95% CI) for
pneumonia was 0.67 (0.48-0.95). Our findings indicate a graded inverse and
independent association between CRF and the future risk of respiratory diseases
in a general male Caucasian population.
PMID- 28698946
TI - Ultra-Sensitive Nano Optical Sensor Samarium-Doxycycline Doped in Sol Gel Matrix
for Assessment of Glucose Oxidase Activity in Diabetics Disease.
AB - A low cost and very sensitive method for the determination of the activity of
glucose oxidase enzyme in different diabetics serum samples was developed. The
method based on the assessment of the H2O2 concentration produced from the
reaction of the glucose oxidase (GOx) enzyme with glucose as substrate in the
serum of diabetics patients by nano optical sensor Sm-doxycycline doped in sol
gel matrix. H2O2 enhances the luminescence intensity of all bands of the nano Sm
doxycycline complex [Sm-(DC)2]+ doped in sol-gel matrix, especially the 645 nm
band at lambdaex = 400 nm and pH 7.0 in water. The influence of the different
analytical parameters that affect the luminescence intensity of the nano optical
sensor, e.g. pH, H2O2 concentration and foreign ions concentrations were studied.
The remarkable enhancement of the luminescence intensity of nano optical sensor
[Sm-(DC)2]+ complex in water at 645 nm by the addition of various concentrations
of H2O2 was successfully used as an optical sensor for the assessment of the
activity of the glucose oxidase enzyme in different diabetics serum samples. The
calibration plot was achieved over the activity range 0.1-240 U/L with a
correlation coefficient of 0.999 and a detection limit of 0.05 U/L.
PMID- 28698947
TI - The effect of cryotherapy on total antioxidative capacity in patients with active
seropositive rheumatoid arthritis.
AB - Patients with rheumatoid arthritis (RA) have increased oxidative stress,
decreased antioxidant levels, and impaired antioxidant capacity. Cold treatments
are used to relieve joint inflammation and pain. Therefore, we measured the
effect of cold treatments on the antioxidative capacity of RA patients with
active disease. Sixty patients were randomized to (1) whole body cryotherapy at
110 degrees C, (2) whole body cryotherapy at -60 degrees C, or (3) local
cryotherapy. Each treatment was given three times daily for 7 consecutive days in
addition to the conventional rehabilitation. Blinded rheumatologist evaluated
disease activity before the first and after the last cryotherapy. We collected
plasma samples daily immediately before the first and after the second
cryotherapy and measured total peroxyl radical trapping antioxidant capacity of
plasma (TRAP), which reflects global combined antioxidant capacity of all
individual antioxidants in plasma. Baseline morning TRAP levels (mean, 95% CI),
adjusted for age, body mass index, disease activity, and dose of prednisolone,
were 1244 (1098-1391) uM/l in the local cryotherapy, 1133 (1022-1245) uM/l in the
cryotherapy at -60 degrees C, and 989 (895-1082) uM/l in the cryotherapy at -110
degrees C groups (p = 0.006). After the first treatment, there was a rise in 1-h
TRAP of 14.2 (-4.2 to 32.6) uM/l, 16.1 (-7.4 to 39.6) uM/l, and 23.6 (4.1-43.2)
uM/l, respectively. The increase was significant in the whole-body cryotherapy
110 degrees C group (p < 0.001) but not significant between the groups (p =
0.78). When analyzed for the whole week, the daily morning TRAP values differed
significantly between the treatment groups (p = 0.021), but there was no
significant change within each treatment group. Whole-body cryotherapy at -110
degrees C induced a short-term increase in TRAP during the first treatment
session with but not during other treatment modalities. The effect was short and
the cold treatments did not cause a significant oxidative stress or adaptation
during 1 week.
PMID- 28698948
TI - piRNA-3878 targets P450 (CpCYP307B1) to regulate pyrethroid resistance in Culex
pipiens pallens.
AB - Piwi-interacting RNAs (piRNAs) are a novel class of noncoding single-strand RNAs.
They play an important role in the germ cell maintenance, brain development,
epigenetic regulation of cancer, and antiviral function. However, little is known
about the relationship between the piRNAs and insecticide resistance in
mosquitoes. In this study, we reported that piRNA-3878 was related with
pyrethroid resistance in Culex pipiens pallens. The expression level of piRNA
3878 was lower in both laboratory and field-collected deltamethrin-resistant (DR)
strains. Overexpression of piRNA-3878 increased the susceptibility of the DR
strain, while inhibiting the expression of piRNA-3878 in DS strain made the
mosquitoes more resistant to deltamethrin. Furthermore, we identified that
CpCYP307B1 was the target of piRNA-3878. The mosquito mortality rate was
increased after downregulating the expression of CpCYP307B1. These findings
revealed that piRNA-3878 could target CpCYP307B1 to regulate pyrethroid
resistance.
PMID- 28698949
TI - Information service in head and neck cancer care-a qualitative study.
AB - AIM: We aimed to understand how information was delivered to head and neck (H&N)
cancer patients and describe the perceptions of the H&N patients concerning
information delivery. METHODOLOGY: This qualitative investigation was a part of
our larger quantitative study that was conducted with H&N cancer patients at two
academic hospitals in Montreal. After obtaining the ethical approval, a
purposeful sample of participants was recruited from the main study until the
content of the information gathered reached saturation. Data were collected by
observing the information delivery and interviewing the study participants and
Nurse Pivots. All observations and interviews were audiotaped. Data were
transcribed verbatim; transcripts were developed, audited, and subjected to a
thematic analysis. RESULTS: Eleven H&N patients participated in the study. We
found that the doctors were the main source of information at both hospitals; one
hospital delivered information systematically to every patient using a multimedia
based information disseminating tool while the second hospital delivered
information verbally in an ad hoc manner. Those who received information using
the multimedia tool understood what was said to them and were better prepared for
the next step, while those who received information verbally did not retain much,
were confused, and expressed dissatisfaction. CONCLUSIONS: Although the doctors
were the main source of information, patients experience difficulties in
understanding what was said to them. Comprehensive information together with
audiovisuals, when provided to H&N cancer patients based on their needs, seems to
improve their understanding of their cancer and prepare them for their treatment.
PMID- 28698950
TI - Outcomes across the return-to-work process in PC survivors attending a
rehabilitation measure-results from a prospective study.
AB - PURPOSE: Approximately 60% of patients are able to work following a cancer
diagnosis. The return-to-work (RTW) process after disability can be
conceptualized as a multi-phase construct. This study investigated RTW outcomes
throughout the RTW process among survivors of prostate cancer (PC) attending a
cancer rehabilitation measure. METHODS: The study was based on a sample of 837
employed PC survivors enrolled in a longitudinal multicenter study. Data was
collected at the beginning of the rehabilitation measure, at the end and at 12
month follow-up by means of self-report questionnaires. We compared outcomes with
regard to age (<60 and >=60 years) and socio-economic status (SES; lower, middle,
higher) using t tests or univariate ANOVA for metrical and chi-square test or
Fisher's exact test for categorical variables. RESULTS: In the off-work phase,
most survivors reported positive expectations regarding future work, including
responsiveness of their work environment. Nevertheless, one fourth intended to
apply for a disability pension. At 12-month follow-up, the RTW rate was 87% and
62% when applying more conservative criteria of RTW. Among survivors who had
returned to work, most reported stability of the work situation. Survivors with
lower SES showed least favorable outcomes throughout the RTW process, while older
age was less consistently of negative impact. CONCLUSIONS: Survivors reported
many favorable RTW outcomes, but low SES might be a barrier at various stages of
the RTW process. Thus, special attention must be paid to the role of social
inequalities during rehabilitation and work reintegration to help survivors
managing the RTW process.
PMID- 28698951
TI - How to report adherence to treatment as clinically relevant data-making a case of
CML and TKI.
PMID- 28698952
TI - Message from the Editor-in-Chief.
PMID- 28698953
TI - What can we do to reduce the associated costs in induction of labour of
intrauterine growth restriction foetuses at term? A cost-analysis study.
AB - OBJECTIVE: To evaluate the costs associated with induction of labour in
intrauterine growth restriction fetuses comparing different procedures. STUDY
DESIGN: 150 pregnancies at term diagnosed with intrauterine growth restriction
and indication for induction of labour were included. 24 were ripened with
misoprostol 25 MUg tablets, 24 with dinoprostone 10 mg vaginal insert, and 77
with Cook(r) cervical ripening balloon. To determine the costs of induction of
labour, method of induction, intrapartum medication, epidural analgesia, type of
delivery, and maternal and neonatal admissions were considered. Statistical
analysis was performed using the G-Stat 2.0 free statistical software. ANOVA test
was used for comparisons between quantitative parametric variables. Chi-squared
test or Fisher test was used for qualitative variables. A value of p < 0.05 was
considered statistically significant. RESULTS: Up to 70.83% women in dinoprostone
group gave birth within the first 24 h compared to 42.66% in misoprostol group
and 36.36% in CG (p < 0.01). Misoprostol tablets were cheaper (9.45 +/- 1.52 US
dollars) than dinoprostone or Cook(r) balloon (41.67 +/- 0 and 59.85 +/- 0 54.45
+/- 0 US dollars, respectively) (p < 0.01). Costs related to maternal admissions
were higher in CG (475.13 +/- 146.95$) than dinoprostone group (475.13 +/-
146.95$) or MG (427.97 +/- 112.65$) (p = 0.03). Total costs in misoprostol group
(2765.18 +/- 495.38$) were lower than in the dinoprostone group (3075.774 +/-
896.14$) or Cook(r) balloon group (3228.02 +/- 902.06$) groups. CONCLUSIONS:
Misoprostol for induction of labour had lower related costs than dinoprostone or
Cook(r) balloon, with similar obstetrical and perinatal outcomes.
PMID- 28698954
TI - Principles of first trimester screening in the age of non-invasive prenatal
diagnosis: screening for other major defects and pregnancy complications.
AB - PURPOSE: First trimester risk assessment plays a major role in the contemporary
pregnancy care. It has evolved significantly since its introduction in the 1990s
when it essentially consisted of just the nuchal translucency measurement. Today,
it involves the measurement of several biophysical and biochemical markers and
can assess the risk for a wide array of major chromosomal and non-chromosomal
defects as well as other pregnancy-related complications. METHODS: A search of
the Medline and Embase databases was done looking for articles about first
trimester screening. We performed a detailed review of the literature to evaluate
the screening tests currently available and their respective test performance.
RESULTS: The detailed ultrasound examination results in the detection of about
half of major structural defects, determination of a very accurate gestational
age, and identification of multiple pregnancies as well as their chorionicity. In
addition, risk assessment for preeclampsia and early IUGR can be established at
this stage. In case of an increased risk, the daily use of low-dose aspirin can
be offered at a point in pregnancy when it still can have a positive impact.
Additional screening tests for gestational diabetes and macrosomia are available.
CONCLUSION: Contemporary first trimester screening is essential to establish an
individual risk profile and can be used to tailor the pregnancy care.
PMID- 28698955
TI - Role of Natural IgM Autoantibodies (IgM-NAA) and IgM Anti-Leukocyte Antibodies
(IgM-ALA) in Regulating Inflammation.
AB - Natural IgM autoantibodies (IgM-NAA) are rapidly produced to inhibit pathogens
and abrogate inflammation mediated by invading microorganisms and host
neoantigens. IgM-NAA achieve this difficult task by being polyreactive with low
binding affinity but with high avidity, characteristics that allow these
antibodies to bind antigenic determinants shared by pathogens and neoantigens.
Hence the same clones of natural IgM can bind and mask host neoantigens as well
as inhibit microorganisms. In addition, IgM-NAA regulate the inflammatory
response via mechanisms involving binding of IgM to apoptotic cells to enhance
their removal and binding of IgM to live leukocytes to regulate their function.
Secondly, we review how natural IgM prevents autoimmune disorders arising from
pathogenic IgG autoantibodies as well as by autoreactive B and T cells that have
escaped tolerance mechanisms. Thirdly, using IgM knockout mice, we show that
regulatory B and T cells require IgM to effectively regulate inflammation
mediated by innate, adaptive and autoimmune mechanisms. It is therefore not
surprising why the host positively selects such autoreactive B1 cells that
generate protective IgM-NAA, which are also evolutionarily conserved. Fourthly,
we show that IgM anti-leukocyte autoantibodies (IgM-ALA) levels and their
repertoire can vary in normal humans and disease states and this variation may
partly explain the observed differences in the inflammatory response after
infection, ischemic injury or after a transplant. Finally we also show how
protective IgM-NAA can be rendered pathogenic under non-physiological conditions.
IgM-NAA have therapeutic potential. Polyclonal IgM infusions can be used to
abrogate ongoing inflammation. Additionally, inflammation arising after ischemic
kidney injury, e.g., during high-risk elective cardiac surgery or after allograft
transplantation, can be prevented by pre-emptively infusing polyclonal IgM, or DC
pretreated ex vivo with IgM, or by increasing in vivo IgM with a vaccine
approach. Cell therapy with IgM pretreated cells, is appealing as less IgM will
be required.
PMID- 28698956
TI - Risk of developing pleural empyema in patients with stroke: a propensity-matched
cohort study.
AB - Pleural empyema is an important complication of pneumonia. Patients with stroke
are at a higher risk developing pneumonia; however, the association between
stroke and pleural empyema risk is largely unknown. We used the data from the
National Health Insurance Research Database of Taiwan to establish a stroke group
consisting of 466,170 patients diagnosed between 2000 and 2010, and a non-stroke
group consisting of the same number of individuals matched by the propensity
score. Incident pleural empyema was monitored toward the end of 2011. Adjusted
hazard ratios (aHRs) of pleural empyema in the stroke group, compared to the non
stroke group, were estimated using the Cox proportional hazards model. We found
that the incidence of pleural empyema is 2.69-fold higher in the stroke group
than in the non-stroke group (15.2 vs. 5.59/10,000 person-years, p < 0.001), with
an aHR of 2.89 [95% confidence interval (CI) = 2.72-3.08]. Further analysis
reveals the aHRs of pleural empyema to be 2.62 (95% CI = 2.45-2.79) in patients
with ischemic stroke and 4.53 (95% CI = 4.14-4.95) in patients with hemorrhagic
stroke compared with those without stroke. In addition, we observe that stroke
patients with ventriculoperitoneal (VP) shunt implantation exhibit more than
sevenfold risk for developing of pleural empyema. In conclusion, patients with
stroke are at an elevated risk of developing pleural empyema. The risk is greater
for those with hemorrhagic stroke than for those with ischemic stroke. The risk
increases further for patients who undergo VP shunt implantation.
PMID- 28698958
TI - Nitrogen Effect on Water-Soluble Polysaccharide Accumulation in Streblonema sp.
(Ectocarpales, Phaeophyceae).
AB - The water-soluble polysaccharides of brown algae attract the increasing attention
of researchers as an important class of polymeric materials of biotechnological
interest. The sole source for production of these polysaccharides has been large
brown seaweeds such as members of Laminariales and Fucales. A new source of water
soluble polysaccharides is suggested here: it is a filamentous brown alga
Streblonema sp., which can be cultivated under controlled conditions in
photobioreactors that allow obtaining algal biomass with reproducible content and
quality of polysaccharides. The accumulation of water-soluble polysaccharides can
be stimulated by macronutrient limitation. In response to nitrogen deficiency,
Streblonema sp. accumulated water-soluble polysaccharides (WSPs) rich in
laminaran. WSP accumulation started after 3-4 days following nitrate depletion
and reached a plateau at around day 7. Polysaccharide accumulation was related to
cellular nitrogen content. The critical internal N level that triggered the onset
of polysaccharide accumulation was 2.3% dry weight (DW); at a cellular N
concentration less than 1.4% DW, the polysaccharide synthesis stopped. Upon
nitrate re-supply, mobilization of WSP occurred after 3 days. These results
suggest that a two-stage cultivation process could be used to obtain large algal
biomass with high water-soluble polysaccharide production: a first cultivation
stage using nitrate-supplemented medium to accumulate algal biomass followed by a
second cultivation stage in a nitrate-free medium for 3 to 7 days to enhance
polysaccharide content in the alga.
PMID- 28698957
TI - The ZJU index is a powerful index for identifying NAFLD in the general Chinese
population.
AB - AIMS: The ZJU index is a novel model for detecting non-alcoholic fatty liver
disease (NAFLD) that it is calculated based on combination of the body mass
index, fasting plasma glucose, triglycerides, and the serum alanine
aminotransferase-to-aspartate transaminase ratio. We aimed to evaluate the
diagnostic accuracy of the ZJU index in detecting NAFLD in the Chinese
population. METHODS: This was a cross-sectional study. Anthropometric
measurements, laboratory data, and ultrasonography features were collected
through a standard protocol. The ZJU index, fatty liver index, hepatic steatosis
index, lipid accumulation product, and visceral adiposity index were calculated.
Then the predictive values of the five indices were compared according to the
area under receiver-operating characteristic curve (AUROC) values. RESULTS: A
total of 19,804 participants were recruited, of whom 7324 participants were
diagnosed with NFALD and 12,480 subjects were regarded as controls. The AUROC
value for NAFLD identification by the ZJU index was 0.925 (95% confidence
interval [CI]: 0.919-0.931), which was significantly higher than the values for
the other four models (P < 0.001). Furthermore, from age 31 years to >60 years,
the AUROC for the ZJU increased from 87.1 to 95.4%, values which were also
greater than those for the other four indices. Analysis by sex also showed that
the performance of the ZJU index in males and females was better than that of the
other four indices. CONCLUSIONS: The ZJU index is an accurate and easy to employ
tool for identifying NAFLD in the general Chinese population.
PMID- 28698959
TI - Isolation and Antibiotic Screening of Fungi from a Hydrothermal Vent Site and
Characterization of Secondary Metabolites from a Penicillium Isolate.
AB - Five new compounds were isolated from Penicillium sp. Y-5-2 including an austin
derivative 4, four isocoumarins 9, 11, 12, and 13, together with two known
isocoumarins 8 and 10, and six known austin derivatives 1, 2, 3, 5, 6, and 7 and
one phenol 14. Their structures and relative configurations were established by
spectroscopic means. The absolute configurations of 4, 11, and 13 were defined
mainly by comparison of quantum chemical TDDFT calculated and experimental ECD
spectra. The cyclization of the pentan-2-ol pendant at C-3 in compound 13 allowed
the assignment of a new 2,3,4,4a,6,10b-hexahydro-1H-benzo[c]chromene isocoumarin
skeleton. New compounds 9, 11, and 13 revealed inhibitory activities against E.
coli at MIC values around 32 MUg/mL. The known compound 14 showed potent
antibiotic activity against Staphylococcus aureus and Bacillus subtilis with MIC
values 8 and 2 MUg/mL, respectively, with no cytotoxicity when tested in vitro. A
rapid and efficient technique for selecting antibiotic fungal strain among eight
marine-derived fungi was also described.
PMID- 28698960
TI - Genome-Wide QTL Analysis Identified Significant Associations Between Hypoxia
Tolerance and Mutations in the GPR132 and ABCG4 Genes in Nile Tilapia.
AB - Exposure to hypoxia induces both acute and chronic stress responses, which plays
an important role in health of cultured organisms including growth, reproduction,
immunity, and other energy demanding activities. Application of advanced genomic
technologies allows rapid identification of hypoxia trait-associated genes and
precise selection of superior brood stocks with high tolerance in tilapia. By
applying QTL-seq and double-digest restriction-site associated DNA sequencing
(ddRAD-seq) techniques, we identified four genome-wide significant quantitative
trait loci (QTLs) for hypoxia tolerance and many suggestive QTLs in Nile tilapia.
These QTLs explained 6.6-14.7% of the phenotypic variance. Further analysis
revealed that single nucleotide polymorphisms (SNPs) in exons of both GPR132 and
ABCG4 genes located in genome-wide QTL intervals were significantly associated
with hypoxia-tolerant traits. Expression analysis of both genes suggested that
they were strong candidate genes involved into hypoxia tolerance in tilapia. Our
findings suggest that both QTL-seq and ddRAD-seq techniques can be effectively
utilized in QTL mapping of hypoxia traits in fish. Our data supply a basis for
further marker-assisted selection of super lines with a high level of tolerance
against low oxygen stress in the tilapia.
PMID- 28698961
TI - [Health policy 2018-there's always the next reform].
PMID- 28698962
TI - [A new model to provide qualified support for urologists : Paramedical staff for
urological continence therapy].
PMID- 28698963
TI - Change in fatty infiltration of lumbar multifidus, erector spinae, and psoas
muscles in asymptomatic adults of Asian or Caucasian ethnicities.
AB - PURPOSE: Fatty infiltration (FI) is a feature of degenerating muscle that
predominates in the low lumbar spine, associates with pain, and is confounded by
age, spinal degeneration, and curvature. We determined rates for decline of
lumbar muscle quality according to ethnicity, muscle, and spinal level in
asymptomatic subjects. METHODS: Cross-sectional simulation study assessing
aggregated data; 650 Asians aged 20-89 years versus 80 Caucasians aged 20-62
years. Change in lumbar multifidus, erector spinae (ES), and psoas fat content
were computed using synthetic data and Monte Carlo simulations. General linear
regression models and multivariate adaptive regression splines enabled estimation
of yearly decline rates [with 95% confidence intervals (CI)]. RESULTS: ES at L1-5
(total) shows steeply reduced density (rate; CI) for Asians in older (>53.3
years) adulthood (-0.32; -0.27 to -0.36/year). For Asians, multifidus (-0.18;
0.15 to -0.20/year) and psoas (-0.04; -0.03 to -0.06/year) also decline, while ES
in younger <=53.3 years) adults does not (0.06; 0.01-0.12/year). Caucasian
multifidus declines (increasing FI % rate; CI) insignificantly faster (L1-5;
0.23; 0.10-0.36%/year) than ES (0.13; 0.04-0.22%/year). Multifidus decline does
not differ between ethnicities. ES in older Asians generally declines fastest
across ethnicities and muscles, and particularly in the low lumbar levels. Low
lumbar levels show higher rates of decline in Asians, with mixed level
dependencies apparent in Caucasians. CONCLUSIONS: Decline in lumbar muscle
composition may differ between ethnicities and muscles. ES and low lumbar levels
appear increasingly susceptible in Asians. Longitudinal studies examining rate of
change to muscle composition may provide distinction between spinal conditions.
PMID- 28698965
TI - What impact do students have on clinical educators and the way they practise?
AB - The clinical education setting plays an important part in teaching students about
the real world of clinical practice. Traditionally the educational relationship
between student and clinical educator has been considered one-way, with students
being the ones that benefit. This review focuses on the areas of clinician
practice and behaviour that students are reported to influence through clinical
placements and as such, determine the overall impact students can have on
supervising clinicians. Electronic searches were conducted across MEDLINE,
EMBASE, PsychINFO and CINAHL in July 2016. Retrieved articles were filtered to
find those which presented data relating to students in the clinical setting.
Data was extracted and analysed independently by two authors through thematic
analysis. Twenty-eight studies met the inclusion criteria. Results showed that
practitioners enjoy the act of teaching. Clinical student presence encourages
clinicians to solidify their knowledge base, stimulates learning and causes them
to re-evaluate their practice. Practitioner skills were further developed as a
results of students. Clinical educator workload and time spent at work increased
when a student was present with time management being the predominant challenge
practitioners faced. Studies demonstrated that clinicians feel they benefit by
students periodically becoming the teacher. Student placements in clinical
practice cause an increase in practitioner workload and lengthen their work day.
These perceived limitations are outweighed by the many benefits described by
supervising clinicians. Providing clinical education can enrich both the
practice, and the practitioner, and the aforementioned advantages should be
highlighted when offering or considering the expansion of clinical placements.
PMID- 28698964
TI - Iatrogenic bilateral hypoglossal palsy following spinal surgery.
AB - INTRODUCTION: Bilateral hypoglossal palsy is a rare complication during airway
management in surgery. CASE PRESENTATION: Isolated bilateral hypoglossal palsy
was noted post-operatively in a patient who underwent multiple spinal surgeries
associated with prone anaesthesia. DISCUSSION: Risk factors include difficult,
multiple intubations, prolonged surgical time, throat pack, and hyperextension of
the neck during intubation. CONCLUSION: We aim to create awareness about this
complication which has a significant morbidity and negative effect on patient
outcomes.
PMID- 28698966
TI - Two skin cell lines from wild-type and albino Japanese flounder (Paralichthys
olivaceus): establishment, characterization, virus susceptibility, efficient
transfection, and application to albinism study.
AB - In order to provide an applicable cell platform to study fish pathology and skin
pigmentation, two cell lines derived from skin tissues of wild-type and albino
Japanese flounder were established and named JFSK_wt and JFSK_alb, respectively.
These two cell lines were cultured for 45 passages within approximately 300 days.
JFSK_wt and JFSK_alb cells were maintained in Dulbecco's Modified Eagle's Medium
and Ham's F-12 Nutrient Mixture (DMEM/F12) supplemented with antibiotics, fetal
bovine serum (FBS), 2-mercaptoethanol (2-Me), N-2-hydroxyethylpiperazine-N'-2
ethanesulfonic acid (HEPES), and basic fibroblast growth factor (bFGF). The
optimal growth temperature for JFSK_wt and JFSK_alb cells was 24 degrees C, and
microscopically, the two cell lines were composed of fibroblast-like cells.
Chromosomal analysis revealed that JFSK_wt and JFSK_alb cells had an identical
diploid karyotype with 2n = 48t. Results of viral inoculation assays revealed
that both cell lines shared similar patterns of viral susceptibility to nervous
necrosis virus (NNV). High transfection efficiency was observed in JFSK_wt and
JFSK_alb cells transfected with a pEGFP-N3 reporter plasmid and Cy3-siRNA. The
detection of dermal marker Dermo-1 showed that these two cells were both derived
from the dermis. Finally, three genes involved in the melanogenesis pathway,
including adenylate cyclase type 5 (adcy5), microphthalmia-associated
transcription factor (mitf), and endothelin B receptor (ednrb), were
downregulated in JFSK_alb versus JFSK_wt cells. Thus, the two cell lines, sampled
from skin tissue of wild-type and albino Japanese flounder will be not only
helpful for fish pathogen research but also beneficial for albinism-related gene
function studies.
PMID- 28698967
TI - Endogenous Expression of ODN-Related Peptides in Astrocytes Contributes to Cell
Protection Against Oxidative Stress: Astrocyte-Neuron Crosstalk Relevance for
Neuronal Survival.
AB - Astroglial cells are important actors in the defense of brain against oxidative
stress injuries. Glial cells synthesize and release the octadecaneuropeptide ODN,
a diazepam-binding inhibitor (DBI)-related peptide, which acts through its
metabotropic receptor to protect neurons and astrocytes from oxidative stress
induced apoptosis. The purpose of the present study is to examine the
contribution of the endogenous ODN in the protection of astrocytes and neurons
from moderate oxidative stress. The administration of H2O2 (50 MUM, 6 h) induced
a moderate oxidative stress in cultured astrocytes, i.e., an increase in reactive
oxygen species, malondialdehyde, and carbonyl group levels, but it had no effect
on astrocyte death. Mass spectrometry and QPCR analysis revealed that 50 MUM H2O2
increased ODN release and DBI mRNA levels. The inhibition of ODN release or
pharmacological blockage of the effects of ODN revealed that in these conditions,
50 MUM H2O2 induced the death of astrocytes. The transfection of astrocytes with
DBI siRNA increased the vulnerability of cells to moderate stress. Finally, the
addition of 1 nM ODN to culture media reversed cell death observed in DBI
deficient astrocytes. The treatment of neurons with media from 50 MUM H2O2
stressed astrocytes significantly reduced the neuronal death induced by H2O2;
this effect is greatly attenuated by the administration of an ODN metabotropic
receptor antagonist. Overall, these results indicate that astrocytes produce
authentic ODN, notably in a moderate oxidative stress situation, and this glio-
and neuro-protective agent may form part of the brain defense mechanisms against
oxidative stress injury.
PMID- 28698968
TI - Inhibition of Poly(ADP-ribose) Polymerase-1 Enhances Gene Expression of Selected
Sirtuins and APP Cleaving Enzymes in Amyloid Beta Cytotoxicity.
AB - Poly(ADP-ribose) polymerases (PARPs) and sirtuins (SIRTs) are involved in the
regulation of cell metabolism, transcription, and DNA repair. Alterations of
these enzymes may play a crucial role in Alzheimer's disease (AD). Our previous
results indicated that amyloid beta (Abeta) peptides and inflammation led to
activation of PARP1 and cell death. This study focused on a role of PARP1 in the
regulation of gene expression for SIRTs and beta-amyloid precursor protein
(betaAPP) cleaving enzymes under Abeta42 oligomers (AbetaO) toxicity in
pheochromocytoma cells (PC12) in culture. Moreover, the effect of endogenously
liberated Abeta peptides in PC12 cells stably transfected with human gene for APP
wild-type (APPwt) was analyzed. Our results demonstrated that AbetaO enhanced
transcription of presenilins (Psen1 and Psen2), the crucial subunits of gamma
secretase. Abeta peptides in APPwt cells activated expression of beta-secretase
(Bace1), Psen1, Psen2, and Parp1. The inhibitor of PARP1, PJ-34 in the presence
of AbetaO upregulated transcription of alpha-secretase (Adam10), Psen1, and
Psen2, but also Bace1. Concomitantly, PJ-34 enhanced mRNA level of nuclear Sirt1,
Sirt6, mitochondrial Sirt4, and Parp3 in PC12 cells subjected to AbetaOs
toxicity. Our data indicated that Abeta peptides through modulation of APP
secretases may lead to a vicious metabolic circle, which could be responsible for
maintaining Abeta at high level. PARP1 inhibition, besides activation of nuclear
SIRTs and mitochondrial Sirt4 expression, enhanced transcription of enzyme(s)
involved in betaAPP metabolism, and this effect should be considered in its
application against Abeta peptide toxicity.
PMID- 28698969
TI - Situating Human Sexual Conditioning.
AB - Conditioning is often thought of as a basic, automatic learning process that has
limited applicability to higher-level human behavior. In addition, conditioning
is seen as separable from, and even secondary to, "innate" processes. These ideas
involve some misconceptions. The aim of this article is to provide a clearer,
more refined sense of human sexual conditioning. After providing some background
information and reviewing what is known from laboratory conditioning studies,
human sexual conditioning is compared to sexual conditioning in nonhumans, to
"innate" sexual responding, and to other types of human learning processes.
Recommendations for moving forward in human sexual conditioning research are
included.
PMID- 28698970
TI - Time is of the Essence: A Review of Electroencephalography (EEG) and Event
Related Brain Potentials (ERPs) in Language Research.
AB - The discovery of electroencephalography (EEG) over a century ago has changed the
way we understand brain structure and function, in terms of both clinical and
research applications. This paper starts with a short description of EEG and then
focuses on the event-related brain potentials (ERPs), and their use in
experimental settings. It describes the typical set-up of an ERP experiment. A
description of a number of ERP components typically involved in language research
is presented. Finally, the advantages and disadvantages of using ERPs in language
research are discussed. EEG has an extensive use in today's world, including
medical, psychology, or linguistic research. The excellent temporal resolution of
EEG information allows one to track a brain response in milliseconds and
therefore makes it uniquely suited to research concerning language processing.
PMID- 28698971
TI - Living with Diabetes: Personal Interviews with Pakistani Women in Norway.
AB - The prevalence of Type 2 diabetes (T2D) among Pakistani women in Norway is
remarkably high. This study aims to assess how they live with the disease and
their response to lifestyle and medical information. 120 Pakistani women living
in Norway (mean age: 55.7 years) were personally interviewed about their T2D
using a structured questionnaire (response rate: 95%). The participants were
first-generation immigrants (mean residence time: 28.7 years) of whom 27% were
illiterates. Poor health was reported by one-third, and 71% had developed
macrovascular comorbidities. A majority reported physical inactivity and an
unhealthy diet included religious fasting. One-third was not able to self-measure
their blood glucose. There was a great variation in antidiabetic drug regimens
and one-fourth had to use insulin in addition to tablets. Pakistani women in
Norway showed suboptimal control of their T2D in terms of lifestyle habits,
comorbidities and drug use. Low literacy and cultural factors seem to challenge
adherence to lifestyle and medical information.
PMID- 28698972
TI - Response Letter.
PMID- 28698973
TI - Contribution of clinical and socioeconomic factors to differences in breast
cancer subtype and mortality between Hispanic and non-Hispanic white women.
AB - PURPOSE: To assess tumor subtype distribution and the relative contribution of
clinical and sociodemographic factors on breast cancer survival between Hispanic
and non-Hispanic whites (NHWs). METHODS: We analyzed data from the California
Cancer Registry, which included 29,626 Hispanic and 99,862 NHW female invasive
breast cancer cases diagnosed from 2004 to 2014. Logistic regression was used to
assess ethnic differences in tumor subtype, and Cox proportional hazard modeling
to assess differences in breast cancer survival. RESULTS: Hispanics compared to
NHWs had higher odds of having triple-negative (OR = 1.29; 95% CI 1.23-1.35) and
HER2-overexpressing tumors (OR = 1.19; 95% CI 1.14-1.25 [HR-] and OR = 1.39; 95%
CI 1.31-1.48 [HR+]). In adjusted models, Hispanic women had a higher risk of
breast cancer mortality than NHW women (mortality rate ratio [MRR] = 1.24; 95% CI
1.19-1.28). Clinical factors accounted for most of the mortality difference (MRR
= 1.05; 95% CI 1.01-1.09); however, neighborhood socioeconomic status (SES) and
health insurance together accounted for all of the mortality difference (MRR =
1.01; 95% CI 0.97-1.05). CONCLUSIONS: Addressing SES disparities, including
increasing access to health care, may be critical to overcoming poorer breast
cancer outcomes in Hispanics.
PMID- 28698974
TI - Successful treatment of chronic refractory pouchitis with vedolizumab.
PMID- 28698975
TI - Exploring the impact of feedback on prescribing error rates: a pilot study.
AB - Background Prescribing errors are prevalent in hospital settings with feedback
identified as one potential error reduction strategy. Hospital pharmacists work
alongside prescribers at ward level and are credible facilitators of prescribing
error feedback. A formalised programme of pharmacist-led prescribing error
feedback was designed and implemented Objective To determine the impact of the
feedback intervention on prescribing error rates. Method Prospective prescribing
audits were undertaken at baseline for control (n = 11) and intervention group (n
= 10) prescribers. The intervention group received pharmacist-led, individualised
constructive feedback on their prescribing, whilst the control group continued
with existing practice. Prescribing was re-audited following 3-months of the
intervention. Data were analysed using chi-squared and independent t-tests.
Results Error frequency (123/641 intervention and 121/649 control) was comparable
between groups at baseline (p = 0.819) with significant differences (90/1677
intervention and 236/984 control) post intervention (p = <0.005). Prescribing
error rates were lower in the intervention group (mean change of -11.5%) and
higher in the control group (mean change of +5.9%) following the intervention,
with a mean significant difference of 17.4% (SD 4.7, 95% CI, -27.3 to -7.6), t =
3.694, p < 0.05, between groups. Conclusion Pharmacist-led prescribing error
feedback positively influences prescribing. This intervention shows promise for
wider application in hospital settings to optimise patient safety.
PMID- 28698976
TI - Medullary Thyroid Cancer: Clinical Characteristics and New Insights into
Therapeutic Strategies Targeting Tyrosine Kinases.
AB - Medullary thyroid carcinoma (MTC) is a hyperplasia of thyroid C-cells, accounting
for 5-10% of all thyroid cancers. MTCs may appear as sporadic or hereditary
forms, and several molecules and signaling pathways have been found to function
defectively in MTC cells. Tyrosine kinases are the most well-studied molecules
that have abnormal function in these tumor cells. Due to their limited response,
chemotherapeutic agents and radiation therapy are not effective in treating
patients with advanced metastatic MTC. In the past decade, significant attention
has been given to the utilization of multikinase inhibitors as targeted
therapeutic agents for treating MTC patients, with the most promising results
arising from the study of tyrosine kinase inhibitors, which generally bind to the
ATP binding sites of these kinases. Two drugs-vandetanib and cabozantinib-are
approved for the treatment of aggressive advanced MTC; however, the potential for
toxicities and adverse effects of these agents on patient quality of life need to
be considered against any therapeutic gain. According to recent data, it appears
that inhibition of only one receptor or molecule in a pathway is not as effective
as simultaneous inhibition of different pathways, indicating the need to use
combination therapy. The main purpose of this review is to describe the clinical
characteristics, molecular mechanisms, and current molecular and targeted
therapeutic strategies active in clinical trials for advanced MTC treatment.
PMID- 28698978
TI - Concentration of 12 Metals and Metalloids in the Blood of White Stork (Ciconia
ciconia): Basal Values and Influence of Age and Gender.
AB - The white stork (Ciconia ciconia) is being increasingly used in biomonitoring
programmes of environmental contaminants due to its growing population in Europe;
however, studies on inorganic elements are scarce. The blood of 70 white storks
was collected and analysed by inductively coupled plasma mass spectroscopy (ICP
MS) to determine the presence of the following elements: lead (Pb), mercury (Hg),
arsenic (As), nickel (Ni), iron (Fe), zinc (Zn), copper (Cu), selenium (Se),
manganese (Mn), chromium (Cr), cobalt (Co), and cadmium (Cd). Our main goals were
to determine the mean concentrations of these elements in the blood and to study
its association with age and gender. Mean concentrations were highest for Fe,
followed by Zn, and lowest for Co and Cd. The metal levels were similar to the
values referred in the literature for the same species from different locations.
No statistically significant differences were found between males and females.
Regarding age, statistically significant differences were observed for Ni, Cu,
Se, Hg, and Pb between young and adult animals (except for Pb, values in adults
were higher than in fledglings). Many element concentrations were correlated,
with the strongest correlations between the pairs Hg-Se, Hg-As, and Fe-Zn, mainly
in adults. This study provides the baseline data for a monitoring program based
on white stork blood as a nondestructive sample.
PMID- 28698977
TI - Pharmacogenetics and Pharmacogenomics of Targeted Therapeutics in Chronic Myeloid
Leukemia.
AB - The advent of targeted therapeutics has greatly improved outcomes of chronic
myeloid leukemia (CML) patients. Despite increased efficacy and better clinical
responses over cytotoxic chemotherapies, many patients receiving targeted drugs
exhibit a poor initial response, develop drug resistance, or undergo relapse
after initial success. This inter-individual variation in response has heightened
the interest in studying pharmacogenetics and pharmacogenomics (PGx) of cancer
drugs. In this review, we discuss the influence of various germline and somatic
factors on targeted drug response in CML. Specifically, we examine the role of
genetic variants in drug metabolism genes, i.e. CYP3A family genes, and drug
transporters, i.e. ABC and SLC family genes. Additionally, we focus on acquired
somatic variations in BCR-ABL1, and the potential role played by additional
downstream signaling pathways, in conferring resistance to targeted drugs in CML.
This review highlights the importance of PGx of targeted therapeutics and its
potential application to improving treatment decisions and patient outcomes.
PMID- 28698979
TI - Effects of supplementing different levels of sun-dried groundnut foliage on
intake, apparent digestibility and nitrogen metabolism in cattle offered a basal
diet of a mixture of rice straw and para grass.
AB - Eight male Cambodian yellow cattle, initial body weight (BW) 136 +/- 11.9 (+/-SD)
kg; age 20 +/- 2.5 (+/-SD) months, were randomly allocated to treatments in a
double 4 * 4 Latin square design to investigate the effects of different levels
of crude protein (CP) from sun-dried groundnut (Arachis hypogaea L.) foliage
(DGF) on feed intake, apparent digestibility and nitrogen metabolism. All animals
were fed a basal diet of rice straw ad libitum and para grass (Brachiaria mutica)
at 1% of BW. The DGF was offered as a supplement at 0, 1, 2 and 3 g CP/kg BW,
denoted DGF0, DGF1, DGF2 and DGF3, respectively. The results showed that the
intake of DGF contributed 0, 25, 34 and 42% of total dry matter (DM) intake. Rice
straw intake decreased when DGF intake increased. Total intake of DM, organic
matter (OM), digestible OM, ash, neutral detergent fibre and acid detergent fibre
increased with increased level of DGF inclusion but did not differ for the two
highest DGF levels. Total DM intake as proportion of BW increased from 2.3% in
DGF0 to 2.8% in DGF3. Crude protein digestibility and nitrogen retention improved
as DGF intake increased. Daily weight gain of DGF1 cattle was higher than DGF0
but was not further improved at the higher levels of DGF inclusion. Microbial
protein synthesis and efficiency of microbial protein production in DGF1 did not
differ from DGF0 but both measures were higher in DGF2 and DGF3. The responses
were diminished at higher DGF inclusion so it is suggested that DGF
supplementation at 1 g CP/kg BW may be the optimal level.
PMID- 28698980
TI - The combined effects of the provision of feed and healthcare on nutrient
utilization and growth performance of sheep during the early or late dry season.
AB - An on-farm study was conducted to determine the combined effects of the provision
of feed and healthcare on nutrient use and growth performance of sheep during the
early or late dry season. A total of 36 smallholder sheep farmers with a flock
size of <=7 was randomly selected within each of the three administrative regions
in Northern Ghana. The sheep grazed on a heterogeneous natural pasture and
offered crop residues as basal diet (control) or were additionally provided with
a concentrate feed plus orthodox healthcare to control diseases and pests (CH) in
a completely randomized block design. The provision of orthodox healthcare
included scheduled control of endo- and ecto-parasites and administration of
broad-spectrum antibiotics. Data was analyzed for the fixed effects of CH,
season, or CH * season using the mixed model procedure of Genstats(r). The CH
regimen had no effect (P = 0.098) on intake of natural pasture but pasture intake
increased (P = 0.012) during the late dry season. Sheep on the CH regime had
higher DM (P = 0.026) and N (P = 0.068) digestibility and improved ADG (P =
0.001) and feed conversion efficiency (P = 0.020) than those on the control. We
hypothesize that improvements in growth performance of sheep on the CH regimen
could be related to availability of nutrients for growth that will otherwise have
been used for repair of damaged tissues caused by gastrointestinal parasites and
ticks. Sheep on the CH regimen also had a higher concentration of fecal N during
the late dry season when CP concentration was relatively higher than that in the
early dry season (63.2 vs 60.9 g/day DM) when CP concentration of pasture was
lower.
PMID- 28698981
TI - Genetically Modified Pigs as Organ Donors for Xenotransplantation.
AB - The growing shortage of available organs is a major problem in transplantology.
Thus, new and alternative sources of organs need to be found. One promising
solution could be xenotransplantation, i.e., the use of animal cells, tissues and
organs. The domestic pig is the optimum donor for such transplants. However,
xenogeneic transplantation from pigs to humans involves high immune
incompatibility and a complex rejection process. The rapid development of genetic
engineering techniques enables genome modifications in pigs that reduce the cross
species immune barrier.
PMID- 28698982
TI - Targeting the reactive intermediate in polysaccharide monooxygenases.
AB - Lytic polysaccharide monooxygenases (LPMOs) are copper metalloenzymes that can
enhance polysaccharide depolymerization through an oxidative mechanism, making
them interesting for the production of biofuel from cellulose. However, the
details of this activation are unknown; in particular, the nature of the
intermediate that attacks the glycoside C-H bond in the polysaccharide is not
known, and a number of different species have been suggested. The homolytic bond
dissociation energy (BDE) has often been used as a descriptor for the bond
activation power, especially for inorganic model complexes. We have employed
quantum-chemical cluster calculations to estimate the BDE for a number of
possible LPMO intermediates to bridge the gap between model complexes and the
actual LPMO active site. The calculated BDEs suggest that the reactive
intermediate is either a Cu(II)-oxyl, a Cu(III)-oxyl, or a Cu(III)-hydroxide,
which indicate that O-O bond breaking occurs before the C-H activation step.
PMID- 28698983
TI - [Hans Franz Edmund Killian - nestor of German anesthesia : Critical appraisal on
the 125th anniversary of his birth].
AB - The surgeon Hans Killian was born on 5 August 1892 in Freiburg im Breisgau,
Germany. Together with the pharmacologist Hellmut Weese and the surgeon Helmut
Schmidt he was one of the nestors of modern German anesthesia. Early on during
his scientific and clinical career, he addressed problems of surgical anesthesia
and in 1928 he became one of the editors of the first German journal of
anesthesia Narcosis and Anesthesia ("Narkose und Anasthesie"). In 1934 he
published the textbook Anesthesia for Surgical Purposes ("Narkose zu operativen
Zwecken"). Between World Wars I and II, he campaigned for anesthesia to become an
independent medical discipline comparable to the situation in the Anglo-Saxon
countries at that time. Because of his merits in the foundation of the German
Society of Anesthesia on 10 April 1953 he became its first honorary member.
Killian died on 7 March 1982 in Freiburg, Germany. Excerpts of his autobiography
which he wrote a few years before his death and which were part of his
inheritance are published here for the first time.
PMID- 28698984
TI - Echocardiographic evaluation of cardiac function after cancer chemotherapy.
AB - Progress in cancer therapy has led to improved prognosis of patients with cancer
and thus to a continuous rise of cancer survivors. However, it has simultaneously
increased cardiovascular morbidity and mortality rates due to direct and/or
indirect side effects of anticancer treatment. Similar to the rapid rise of
patients with adult congenital disease, the number of patients suffering or at
risk of cardiotoxicity has been steeply increasing and getting an emerging issue.
Among the many facets of chemotherapy-induced cardiovascular toxicity, this
review attempts to summarize echocardiographic evaluation of cardiac function
after cancer chemotherapy by reviewing the definition, risk factors, brief
history, limitation of left ventricular ejection fraction and myocardial strain
imaging, as well as the limitations of this technique.
PMID- 28698985
TI - A cinnamon-derived procyanidin type A compound inhibits hepatitis C virus cell
entry.
AB - BACKGROUND AND AIMS: Chronic hepatitis C virus (HCV) infection is a major cause
of liver disease worldwide. Although direct-acting antivirals can cure the large
majority of treated patients, important limitations remain, including treatment
failure and high costs precluding access to therapy in resource-limited settings.
We report herein the anti-HCV effects of IND02, a procyanidin type A molecule,
isolated and characterized from cinnamon. METHODS AND RESULTS: Using cellculture
derived HCV (HCVcc), HCV pseudoparticles (HCVpp), and subgenomic replicons, we
demonstrated that IND02 markedly and dose-dependently inhibited HCV cell entry.
Kinetic assays demonstrated that IND02 inhibits HCV entry most likely at a
postbinding step. Experiments performed using primary human hepatocytes confirmed
inhibition of HCV entry by IND02, demonstrating the functional impact in the most
physiological cell-based system for studying HCV-host interactions. CONCLUSIONS:
The natural compound IND02 exhibits potent HCV cell entry inhibition and provides
a novel perspective for development of a low-cost antiviral for treatment of HCV
infection.
PMID- 28698986
TI - Novelties in the pathophysiology and management of portal hypertension: new
treatments on the horizon.
AB - Portal hypertension (PH) is responsible for the most severe complications of
cirrhosis and leading cause of death and liver transplantation. The standard
pharmacological treatment available for PH currently consists of the use of a non
selective beta-blocker. However, a significant proportion of patients do not
respond to pharmacological treatment. This has led to the development of
identifiable targets for the discovery of new horizons in PH treatment. Recently,
there has been significant progress in understanding the mechanism behind PH,
which is a product of increased hepatic vascular resistance including structural
changes and functional change due to endothelial dysfunction. Moreover, increased
portal inflow is the outcome of dilation of splanchnic vessels and hyperdynamic
circulation. Here, challenges in formulating potential pharmacological treatment
as well as current potential targets for PH will be reviewed. During the past
decades, there have been many efforts to explore new techniques to stimulate
liver regeneration in addition to pharmacological treatment. The bone marrow (BM)
stem cells which differentiate into mature hepatocytes are thought to contribute
to liver regeneration and have been found to demonstrate great potential as
regenerative medicine in different therapeutic applications. Based on these
insights, we explore the current and potential novel therapeutic uses of BM stem
cell therapy in PH.
PMID- 28698987
TI - The effects of traditional, superset, and tri-set resistance training structures
on perceived intensity and physiological responses.
AB - PURPOSE: Investigate the acute and short-term (i.e., 24 h) effects of traditional
(TRAD), superset (SS), and tri-set (TRI) resistance training protocols on
perceptions of intensity and physiological responses. METHODS: Fourteen male
participants completed a familiarisation session and three resistance training
protocols (i.e., TRAD, SS, and TRI) in a randomised-crossover design. Rating of
perceived exertion, lactate concentration ([Lac]), creatine kinase concentration
([CK]), countermovement jump (CMJ), testosterone, and cortisol concentrations was
measured pre, immediately, and 24-h post the resistance training sessions with
magnitude-based inferences assessing changes/differences within/between
protocols. RESULTS: TRI reported possible to almost certainly greater efficiency
and rate of perceived exertion, although session perceived load was very likely
lower. SS and TRI had very likely to almost certainly greater lactate responses
during the protocols, with changes in [CK] being very likely and likely increased
at 24 h, respectively. At 24-h post-training, CMJ variables in the TRAD protocol
had returned to baseline; however, SS and TRI were still possibly to likely
reduced. Possible increases in testosterone immediately post SS and TRI protocols
were reported, with SS showing possible increases at 24-h post-training. TRAD and
SS showed almost certain and likely decreases in cortisol immediately post,
respectively, with TRAD reporting likely decreases at 24-h post-training.
CONCLUSIONS: SS and TRI can enhance training efficiency and reduce training time.
However, acute and short-term physiological responses differ between protocols.
Athletes can utilise SS and TRI resistance training, but may require additional
recovery post-training to minimise effects of fatigue.
PMID- 28698988
TI - Medication Errors: A Characterisation of Spontaneously Reported Cases in
EudraVigilance.
AB - INTRODUCTION: Medication errors recently became the focus of regulatory guidance
in pharmacovigilance to support reporting, evaluation and prevention of
medication errors. OBJECTIVE: This study aims to characterise spontaneously
reported cases of medication errors in EudraVigilance over the period 2002-2015
before the release of EU good practice guidance. METHODS: Case reports were
identified through the adverse reaction section where a Medical Dictionary for
Regulatory Activities (MedDRA(r)) term is reported and included in the
Standardised MedDRA(r) Query (SMQ) for medication errors. These case reports were
further categorised by MedDRA(r) terms, geographical region, patient age group
and Anatomical Therapeutic Chemical classification system of suspect medicinal
product(s). RESULTS: A total of 147,824 case reports were retrieved, 41,355 of
which were from the European Economic Area (EEA). Approximately 60% of these case
reports were retrieved with the narrow SMQ. The absolute number of medication
error case reports and the proportion to the total number of reports in
EudraVigilance increased during the study period, with peaks seen around 2005 and
2012 for cases with EEA origin. Fifty-two percent of case reports in which age
was provided occurred in adults, 30% in the elderly and 18% in children, with
almost half of these in children aged 2 months to 2 years. CONCLUSION: Case
reports of medication errors in EudraVigilance steadily increased between 2005
and 2015, the reasons for which may be multifactorial, including increased
awareness, changes to the MedDRA(r) terminology and the 2012 EU pharmacovigilance
legislation and associated guidance for stakeholders, or a generally increased
risk for errors as more medications become available.
PMID- 28698989
TI - Acquisition of habitual visual attention and transfer to related tasks.
AB - Extensive research has shown that statistical learning affects perception,
attention, and action control; however, few studies have directly linked
statistical learning with the formation of habits. Evidence that learning can
induce a search habit has come from location probability learning, in which
people prioritize locations frequently attended to in the past. Here, using an
alternating training-testing procedure, we demonstrated that the initial
attentional bias arises from short-term intertrial priming, whereas probability
learning takes longer to emerge, first reaching significance in covert orienting
(measured by reaction times) after about 48 training trials, and in overt
orienting (measured by eye movements) after about 96 training trials. We further
showed that location probability learning is persistent after training is
discontinued, by transferring from a letter search task to a scene search task
emulating another characteristic feature of habits. By identifying the onset of
probability learning and investigating its task specificity, this study provides
evidence that probability cuing can induce habitual spatial attention.
PMID- 28698990
TI - Explanation-based learning in infancy.
AB - In explanation-based learning (EBL), domain knowledge is leveraged in order to
learn general rules from few examples. An explanation is constructed for initial
exemplars and is then generalized into a candidate rule that uses only the
relevant features specified in the explanation; if the rule proves accurate for a
few additional exemplars, it is adopted. EBL is thus highly efficient because it
combines both analytic and empirical evidence. EBL has been proposed as one of
the mechanisms that help infants acquire and revise their physical rules. To
evaluate this proposal, 11- and 12-month-olds (n = 260) were taught to replace
their current support rule (that an object is stable when half or more of its
bottom surface is supported) with a more sophisticated rule (that an object is
stable when half or more of the entire object is supported). Infants saw teaching
events in which asymmetrical objects were placed on a base, followed by static
test displays involving a novel asymmetrical object and a novel base. When the
teaching events were designed to facilitate EBL, infants learned the new rule
with as few as two (12-month-olds) or three (11-month-olds) exemplars. When the
teaching events were designed to impede EBL, however, infants failed to learn the
rule. Together, these results demonstrate that even infants, with their limited
knowledge about the world, benefit from the knowledge-based approach of EBL.
PMID- 28698991
TI - A prospective, randomized trial comparing thulium vapoenucleation with holmium
laser enucleation of the prostate for the treatment of symptomatic benign
prostatic obstruction: perioperative safety and efficacy.
AB - INTRODUCTION AND OBJECTIVES: To compare the perioperative outcomes of thulium
vapoenucleation of the prostate (ThuVEP) with holmium laser enucleation of the
prostate (HoLEP) for patients with symptomatic benign prostatic obstruction
(BPO). METHODS: Forty-eight and 46 patients were prospectively randomized to
ThuVEP and HoLEP. All patients were assessed preoperatively and 4-week
postoperatively. The complications were noted and classified according to the
modified Clavien classification system. Patient data were expressed as median
(interquartile range) or numbers (%). RESULTS: Median age at surgery was 73 (67
76) years and median prostate volume was 80 (46.75-100) cc and not different
between the groups (p = 0.207). The median operative time was 60 (41-79) minutes
without significant differences between both groups (p = 0.275). There were no
significant differences between the groups regarding catheterization time [2 (2
2) days, p = 0.966] and postoperative stay [2 (2-3) days, p = 0.80]). Clavien 1
(13.8%), Clavien 2 (3.2%), Clavien 3a (2.1%), and Clavien 3b (4.3%) complications
occurred without significant differences between the groups. However, the
occurrence of acute postoperative urinary retention was higher after HoLEP
compared to ThuVEP (15.2 vs. 2.1%, p <= 0.022). At 1-month follow-up, peak
urinary flow rates (10.7 vs. 22 ml/s), post-void residual volumes (100 vs. 20
ml), International Prostate Symptom Score (20 vs. 10) and Quality of Life (4 vs.
3) had improved significantly (p <= 0.005) without significant differences
between the groups. CONCLUSIONS: ThuVEP and HoLEP are safe and effective
procedures for the treatment of symptomatic BPO. Both procedures give equivalent
and satisfactory immediate micturition improvement with low perioperative
morbidity.
PMID- 28698992
TI - Reply to the Letter: "Direct Transarterial Embolization with N-Butyl-2
Cyanoacrylate Should be the Choice of Treatment for Spontaneous Hematomas in
Patients on Anticoagulation Treatment".
PMID- 28698993
TI - Direct Transarterial Embolization with n-Butyl-2-Cyanoacrylate Should be the
Choice of Treatment for Spontaneous Hematomas in Patients on Anticoagulation
Treatment.
PMID- 28698994
TI - Prognostic importance of sodium level trajectory in acute heart failure.
AB - Low sodium levels are strongly associated with poor prognosis in acute heart
failure (AHF); however, the prognostic impact of the sodium level trajectory
overtime has not been determined. A secondary analysis of the AQUAMARINE study in
which patients with AHF and renal impairment were randomized to receive either
tolvaptan or conventional treatment was performed. Sodium levels were evaluated
at the baseline and at 6, 12, 24, and 48 h. We defined 'sodium dipping' as sodium
level falling below the baseline level at any time point. The primary endpoint
was the combined event of all-cause death and heart failure rehospitalization
during follow-up. The analysis included 184 patients with a median follow-up of
21.1 months. Sodium levels more steeply increased during the 48 h in patients
without events as compared to sodium levels in patients with events (P = 0.018 in
linear-mixed effect model). The sodium dipping group (n = 100; 54.3%)
demonstrated significantly less urine output, less body weight reduction, and
poorer diuretic response within 48 h compared to the non-dipping group. The
sodium dipping group was also significantly associated with a low combined-event
free survival after adjustment for other prognostic factors (HR 1.97; 95% CI 1.06
3.38; P = 0.033). The trajectory of sodium levels during the acute phase is
associated with the prognosis of patients with AHF independently of the baseline
sodium level.
PMID- 28698995
TI - Transradial versus transfemoral approach in patients undergoing primary
percutaneous coronary intervention for ST-elevation acute myocardial infarction:
insight from the CREDO-Kyoto AMI registry.
AB - Recent randomized clinical trials demonstrated that transradial approach was a
preferred approach for primary percutaneous coronary intervention (PCI) in ST
elevation acute myocardial infarction (STEMI). However, clinical outcomes of
transradial approach in STEMI have not been adequately evaluated yet in the real
world practice, which includes hemodynamically unstable high-risk patients. We
identified 3662 STEMI patients who had primary PCI within 24 h after symptom
onset and were treated by transradial (N = 471) or transfemoral (N = 3191)
approach in the CREDO-Kyoto AMI registry. In the current analysis, we compared
clinical characteristics and long-term outcomes between the 2 groups of patients
treated by transradial approach and transfemoral approach. The prevalence of
hemodynamically compromised patients (Killip II-IV) was significantly less in the
transradial group than in the transfemoral group (19 vs. 25%, P = 0.002).
Cumulative 5-year incidences of death/MI/stroke, and major bleeding were not
significantly different between the transradial and transfemoral groups (26.7 vs.
25.9%, log-rank P = 0.91, and 11.3 vs. 11.5%, log-rank P = 0.71, respectively).
After adjustment for confounders, the risks of the transradial group relative to
the transfemoral group were not significant for both death/MI/stroke [Hazard
ratio (HR) 1.15, 95% confidence interval (CI) 0.83-1.59, P = 0.41] and major
bleeding (HR 1.29, 95% CI 0.77-2.15, P = 0.34). In the subgroup of
hemodynamically compromised patients, there were also no significant differences
in the risks for death/MI/stroke and major bleeding between the 2 groups.
Clinical outcomes of transradial approach were not different from those of
transfemoral approach in primary PCI for STEMI in the real-world practice.
PMID- 28698996
TI - Genome sequencing of strain Cellulosimicrobium sp. TH-20 with ginseng
biotransformation ability.
AB - Biotransformation for increasing the pharmaceutical effect of ginsenosides is
getting more and more attractions. Strain Cellulosimicrobium sp. TH-20 isolated
from ginseng soil samples was identified to produce enzymes contributing to its
excellent biotransformation activity against ginsenosides, the main active
components of ginseng. Based on phylogenetic tree and homology analysis, the
strain can be designated as Cellulosimicrobium sp. Genome sequencing was
performed using the Illumina Miseq to explore the functional genes involved in
ginsenoside transformation. The draft genome of Cellulosimicrobium sp. TH-20
encoded 3450 open reading frames, 51 tRNA, and 9 rRNA. All ORFs were annotated
using NCBI BLAST with non-redundant proteins, Gene Ontology, Cluster of
Orthologous Gene, and Kyoto Encyclopedia of Genes and Genomes databases. A total
of 11 genes were selected based on the functional annotation analysis. These
genes are relevant to ginsenoside biotransformation, including 6 for beta
glucosidase, 1 for alpha-N-arabinofuranosidase, 1 for alpha-1,6-glucosidase, 1
for endo-1,4-beta-xylanase, 1 for alpha-L-arabinofuranosidase, and 1 for beta
galactosidase. These glycosidases were predicted to catalyze the hydrolysis of
sugar moieties attached to the aglycon of ginsenosides and led to the
transformation of PPD-type and PPT-type ginsenosides.
PMID- 28698997
TI - Zinc oxide-curcumin nanocomposite loaded collagen membrane as an effective
material against methicillin-resistant coagulase-negative Staphylococci.
AB - Zinc oxide nanoparticles and curcumin are excellent antimicrobial agents. They
have the potential to be used as alternative to antibiotics in wound infection
management. In this study, ZnO-curcumin nanocomposite was synthesized and
characterized. Physical adsorption of the nanocomposite onto collagen skin wound
dressing was conducted and structural investigation was carried out by SEM.
Antimicrobial assay, minimum inhibitory concentration (MIC), and viability assays
of different concentrations of nanocomposite loaded collagen membrane were
conducted against clinically isolated methicillin-resistant coagulase-negative
Staphylococci (MRCoNS), such as S. epidermidis, S. hemolyticus, and S.
saprophyticus. The nanocomposite showed excellent anti-CoNS activity on time kill
assay with the MIC value of 195 ug/mL against S. epidermidis, S. hemolyticus and
390 ug/mL against S. saprophyticus. The nanocomposite loaded collagen membrane
also showed excellent in vitro antistaphylococcal activity. This study may lead
to the development of antibiotic alternate strategies to control and limit the
MRCoNS in wound-related infections.
PMID- 28698998
TI - Does organ selling violate human dignity?
AB - Shortages in the number of donated organs after death and the growing number of
end-stage organ failure patients on waiting lists call for looking at
alternatives to increase the number of organs that could be used for
transplantation purposes. One option that has led to a legal and ethical debate
is to have regulated markets in human organs. Opponents of a market in human
organs offer different arguments that are mostly founded on contingent factors
that can be adjusted. However, some authors have asked the question whether we
still have a reason to believe that there is something wrong with offering human
organs for sale for transplantation purposes, even if the circumstances under
which the practice takes place are improved. One prominent argument regarding
this appeals to the notion of human dignity. It is argued that organ selling
violates human dignity. This paper presents a systematic discussion of dignity
based arguments in the organ selling debate, and then develops a social account
of dignity. It is argued that allowing the practice of organ selling inherently
runs the risk of promoting the notion that some persons have less worth than
others and that persons have a price, which is incompatible with dignity. The
approach is defended against possible objections and it is shown that it can
capture the notion that autonomy is linked to human dignity in important ways,
while dignity at the same time can constrain the autonomous choices of persons
with regards to certain practices.
PMID- 28698999
TI - Long-term effectiveness and moderators of a web-based tailored intervention for
cancer survivors on social and emotional functioning, depression, and fatigue:
randomized controlled trial.
AB - PURPOSE: The web-based computer-tailored Kanker Nazorg Wijzer (Cancer Aftercare
Guide) supports cancer survivors with psychosocial issues during cancer recovery.
The current study investigates whether the 6-month effects in increasing
emotional and social functioning and reducing depression and fatigue hold at 12
months from baseline. Moreover, it explores whether patient characteristics
moderate the 6- and 12-month intervention effectiveness. METHODS: Cancer
survivors from 21 Dutch hospitals (November 2013-June 2014) were randomized to an
intervention (n = 231) or a wait-list control group (n = 231). Intervention
effects on emotional and social functioning (EORTC QLQ-C30), depression (HADS),
and fatigue (CIS) were evaluated through multilevel linear regression analyses.
RESULTS: At 12 months from baseline, the intervention group no longer differed
from the control group in emotional and social functioning, depression, and
fatigue. Moderator analyses indicated that, at 6 months, the intervention was
effective in improving social functioning for men (d = 0.34), reducing fatigue
for participants <=56 years (d = 0.44), and reducing depression for participants
who received chemotherapy (d = 0.36). At 12 months, participants with a medium
educational level reported higher social functioning (d = 0.19), while
participants with a low educational level reported lower social functioning (d =
0.22) than participants with a similar educational level in the control group.
CONCLUSIONS: The intervention gave cancer patients a head start to psychological
recovery after the end of cancer treatment. The control group caught up in the
long run. IMPLICATIONS FOR CANCER SURVIVORS: The Cancer Aftercare Guide expedited
recovery after cancer treatment. Being a low intensity, easy accessible, and
relatively low cost intervention, it could serve as a relevant step in recovery
and stepped care.
PMID- 28699000
TI - Nature diversity and well-being in old age.
AB - BACKGROUND: The research aim was to study the associations of nature diversity
with quality of life (QoL) and depressive symptoms among older people, and
whether physical activity explains the associations. METHODS: Community-dwelling
people aged 75-90 years (n = 848) living in Central Finland were interviewed in
their homes. QoL was assessed with a short version of the World Health
Organization Quality-of-Life Assessment (range 0-130, higher score indicates
better QoL) and depressive symptoms with the Centre for Epidemiologic Studies
Depression Scale (range 0-30, higher scores indicate more depressive symptoms).
Self-reported physical activity was assessed by intensity and duration using a
single question with seven response options ranging from mostly resting to
competitive sports. Nature diversity (Shannon Diversity Index) was assessed
objectively within a 500-m buffer around participants' homes using a geographic
information system (GIS). RESULTS: Mean QoL was 100.3 (SD 11.8) and mean CES-D
9.6 (SD 6.8). Those in the highest nature diversity tertile had better QoL than
those in the lowest tertile (p = .022). Physical activity did not explain the
association between nature diversity and QoL. Adjustment for health indicators
did not change the results. Nature diversity was not associated with depressive
symptoms. CONCLUSION: A diverse environment, especially when this includes
elements of nature, is associated with better QoL. Good quality of the green
infrastructure and adding natural elements to residential areas may enhance well
being among community-dwelling older people.
PMID- 28699001
TI - Identification, classification and transcriptional profiles of dirigent domain
containing proteins in sugarcane.
AB - Dirigent (DIR) proteins, encoded by DIR genes, are referred to as "dirigent"
because they direct the outcome of the coupling of the monolignol coniferyl
alcohol into (+) or (-) pinoresinol, the first intermediates in the
enantiocomplementary pathways for lignan biosynthesis. DIR domain-containing or
DIR-like proteins are, thus, termed for not having a clear characterization. A
transcriptome- and genome-wide survey of DIR domain-containing proteins in
sugarcane was carried out, in addition to phylogenetic, physicochemical and
transcriptional analyses. A total of 120 non-redundant sequences containing the
DIR domain were identified and classified into 64 groups according to
phylogenetic and sequence alignment analyses. In silico analysis of transcript
abundance showed that these sequences are expressed at low levels in leaves and
genes in the same phylogenetic clade have similar expression patterns. Expression
analysis of ShDIR1-like transcripts in the culm internodes of sugarcane
demonstrates their abundance in mature internodes, their induction by nitrogen
fertilization and their predominant expression in cells that have a lignified
secondary cell wall, such as vascular bundles of young internodes and parenchymal
cells of the pith of mature internodes. Due to the lack of information about the
functional role of DIR in plants, a possible relationship is discussed between
the ShDIR1-like transcriptional profile and cell wall development in parenchyma
cells of sugarcane culm, which typically accumulates large amounts of sucrose.
The number of genes encoding the DIR domain-containing proteins in sugarcane is
intriguing and is an indication per se that these proteins may have an important
metabolic role and thus deserve to be better studied.
PMID- 28699002
TI - A bilateral approach to extended thymectomy using the da Vinci Surgical System
for patients with myasthenia gravis.
AB - PURPOSE: We adopted a bilateral approach to complete robotic extended thymectomy
with the excision of the pericardial fat tissue from both sides and analyzed the
initial outcomes. METHODS: The patient cart was docked first from the left
shoulder side. After dissection of the thymus and right pericardial fat tissue,
the cart was temporarily rolled out, and the bed was rotated approximately 90
degrees clockwise. The cart was then re-docked from the right-side shoulder, and
extended thymectomy was performed via the left-side approach. The outcomes were
compared with four cases of unilateral approach performed for mediastinal tumor
in the same term. RESULTS: Four patients with myasthenia gravis (two of whom had
stage I thymoma) underwent extended thymectomy by the bilateral approach. The
mean operative time was 288 min, and the console time was 146 min in the right
side and 67 min in the left side. The resected thymus and surrounding adipose
tissue were almost symmetrical, in contrast with those obtained via the
unilateral approach. No remarkable events were noted. CONCLUSION: Bilateral
extended thymectomy for myasthenia gravis patients was safe and reasonable based
on the initial outcomes.
PMID- 28699003
TI - Sarcopenia is an independent predictor of complications after colorectal cancer
surgery.
AB - PURPOSE: The significance of sarcopenia after colorectal cancer (CRC) resection
has only been discussed with relatively small samples or short follow-up periods.
This study aimed to clarify the clinical significance of sarcopenia in a large
sample study. METHODS: We retrospectively analyzed the relationship between
sarcopenia and clinical factors, surgical outcomes, and the survival in 494
patients who underwent CRC surgery between 2004 and 2013. Sarcopenia was defined
based on the sex-specific skeletal muscle mass index measured by preoperative
computed tomography. RESULTS: Sarcopenia was associated with sex (higher rate of
male, P < 0.0001), and low body mass index (P < 0.0001), but not age or tumor
stage. Sarcopenia was associated with higher incidence of all postoperative
complications (P = 0.02), especially for patients with Clavien-Dindo
classification grade >=2 (CDC; P = 0.0007). Postoperative hospital stays were
significantly longer for sarcopenic patients than for non-sarcopenic patients (P
= 0.02). In a multivariate analysis, sarcopenia was an independent predictor for
postoperative complications (P = 0.01, odds ratio 1.82, 95% confidence interval
1.13-3.00). Among postoperative complications (CDC grade >=2), sarcopenia was
correlated with non-surgical-site infections (P = 0.03). Sarcopenia was not
correlated with the overall or recurrence-free survival. CONCLUSIONS: Sarcopenia
was an independent predictive factor for postoperative complications after CRC
surgery.
PMID- 28699004
TI - A delayed proinflammatory response of human preadipocytes to PCB126 is dependent
on the aryl hydrocarbon receptor.
AB - Inflammation in adipose tissue is recognized as a causative factor in the
development of type II diabetes. Adipocyte hypertrophy as well as bacterial and
environmental factors have been implicated in causing inflammation in mature
adipocytes. Exposure to persistent organic pollutants such as polychlorinated
biphenyls (PCBs) has been associated with the development of type II diabetes. We
show here that PCB126, a dioxin-like PCB, activates a robust proinflammatory
state in fat cell precursors (preadipocytes). The response was found to be
dependent on aryl hydrocarbon receptor (AhR) activation, although induction of
the response was delayed compared to upregulation of CYP1A1, a classic AhR
responsive gene. Treatment of preadipocytes with a nuclear factor kappa-light
chain-enhancer of activated B cell (NF-kappaB) inhibitor partially attenuated the
PCB126-induced inflammatory response and partly, but not completely, ameliorated
disruption of adipogenesis caused by PCB126. Our results indicate a role for
PCB126 in mediating an inflammatory response through AhR in preadipocytes that
interferes with adipogenesis.
PMID- 28699005
TI - Study of chlordecone desorption from activated carbons and subsequent
dechlorination by reduced cobalamin.
AB - Since 1972, the French departments of Guadeloupe and Martinique have intensively
used organochlorinated pesticides such as chlordecone (CLD) and
hexachlorocyclohexane (HCH) isomers to prevent the proliferation of banana weevil
(Cosmopolite sordidus). These molecules are stable in the environment, leading to
a continuous contamination of soils, water, and food chain in the banana
producing areas. In these polluted areas, water treatment plants are equipped
with activated carbon (AC) filters. In order to improve treatment of CLD
contaminated waters by AC, CLD adsorption and desorption kinetic studies are
carried out using different ACs produced from sugar cane bagasse as adsorbents
and subsequent CLD degradation is performed using reduced vitamin B12 (VB12). A
GC-MS method for CLD quantification is as well optimized. This study shows that
bagasse ACs are able to capture the pollutant, leading to a CLD concentration
decrease from 1 to 73 MUg L-1, with an adsorption capacity of 162 MUg mg-1.
Adsorption capacity increase with the temperature indicates an endothermic
process. Polar solvents favor CLD desorption from ACs, suggesting hydrogen
bonding between CLD and surface groups of ACs, the best solvent for chemical
desorption being ethanol. Subsequent degradation of CLD in ethanol is performed
using vitamin B12 reduced by either 1,4-dithiotreitol (DTT) or zerovalent zinc,
leading to 90% of CLD removal and to the molecule cage structure opening for
formation of a pentachloroindene intermediate product, characterized by GC MS/MS.
A pathway for pentachloroindene formation from CLD is proposed.
PMID- 28699006
TI - Adsorption and mineralization of REE-lanthanum onto bacterial cell surface.
AB - A large number of rare earth element mining and application resulted in a series
of problems of soil and water pollution. Environmental remediation of these REE
contaminated sites has become a top priority. This paper explores the use of
Bacillus licheniformis to adsorb lanthanum and subsequent mineralization process
in contaminated water. The maximum adsorption capacity of lanthanum on bacteria
was 113.98 mg/g (dry weight) biomass. X-ray diffraction (XRD) and transmission
electron microscopy (TEM) data indicated that adsorbed lanthanum on bacterial
cell surface occurred in an amorphous form at the initial stage. Scanning
electron microscopy with X-ray energy-dispersive spectroscopy (SEM/EDS) results
indicated that lanthanum adsorption was correlated with phosphate. The amorphous
material was converted into scorpion-like monazite (LaPO4 nanoparticles) in a
month. The above results provide a method of using bacterial surface as
adsorption and nucleation sites to treat REE-contaminated water.
PMID- 28699007
TI - Assessment of nonsteroidal anti-inflammatory drugs by ultrasonic-assisted
extraction and GC-MS in Mgeni and Msunduzi river sediments, KwaZulu-Natal, South
Africa.
AB - The occurrence of eight pharmaceuticals was monitored during four seasons
(spring, summer, autumn, and winter) along a 250-km stretch of the Msunduzi and
Mgeni rivers in KwaZulu-Natal, South Africa. This paper describes an optimized
method for the determination of nonsteroidal anti-inflammatory drugs (NSAIDs) in
sediments. The method combines ultrasonic, centrifuge, and gas chromatography
mass spectrometry for the detection of these drugs in solid samples. Most of the
parameters that affect the extraction step were optimized. Solid samples were
placed in a centrifuge tube and extracted with ethyl acetate:acetone (1:1, two
cycles), followed by clean-up with Oasis HLB cartridge and derivatization with N,
O-bis(trimethylsilyl) trifluoroacetamide (BSTFA). Satisfactory recoveries were
obtained ranging from 66 to 130%, depending on the analyte. Precision expressed
as RSD (%) (n = 3) was less than 20% for all analytes. The LODs and LOQs were in
the range of 0.024 to 1.90 ng g-1 which allowed to be applied in the analysis
solid samples in Msunduzi and Mgeni rivers. In the solid samples analyzed, NSAID
concentration ranged from not detected to 221 ng g-1.
PMID- 28699008
TI - Fe3O4 nanoparticle-encapsulated mesoporous carbon composite: An efficient
heterogeneous Fenton catalyst for phenol degradation.
AB - Magnetite (Fe3O4) nanoparticle-encapsulated mesoporous carbon nanocomposite was
fabricated from Fe-based metal-organic framework (MOF) (MIL-102) through
carbonization. It was found that Fe-based MOF (MIL-102) is a potential precursor
for the fabrication of hexagonal mesoporous carbon nanodisk functionalized with
Fe3O4 nanoparticles. The obtained nanocomposite was characterized by XRD, FT-IR,
N2 adsorption and desorption, FE-SEM and HRTEM techniques. As a Fenton-like solid
catalyst for phenol degradation, Fe3O4 nanoparticle-encapsulated mesoporous
carbon showed greater catalytic activity for the production of hydroxyl radical
from the decomposition of H2O2 and it accomplished 100% phenol and 82% total
organic carbon (TOC) conversion, within 120 min of reaction. This enhanced
catalytic performance was due to confined access for the pollutant to the iron
oxide nanoparticles provided by mesopores in carbon shell. Bare Fe3O4 nanodisk
shows poor catalytic performance in the degradation of phenol, and it obviously
reveals the significance of the mesoporous carbon support for iron oxide
nanoparticles.
PMID- 28699009
TI - Bio-fabrication of silver nanoparticles using the leaf extract of an ancient
herbal medicine, dandelion (Taraxacum officinale), evaluation of their
antioxidant, anticancer potential, and antimicrobial activity against
phytopathogens.
AB - In recent years, the use of nanoparticle-based antimicrobials has been increased
due to many advantages over conventional agrochemicals. This study investigates
the utilization of common medicinal plant dandelion, Taraxacum officinale, for
the synthesis of silver nanoparticles (TOL-AgNPs). AgNPs were evaluated for
antimicrobial activity against two important phytopathogens, Xanthomonas
axonopodis and Pseudomonas syringae. The morphology, size, and structure of TOL
AgNPs were characterized using UV-visible spectroscopy and X-ray diffraction
(XRD). Fourier transform infrared spectroscopy (FT-IR) showed the presence of
phytochemicals involved during synthesis of NPs. High-resolution transmission
electron microscopy (HR-TEM) analysis shed light on the size of monodispersed
spherical AgNPs ranging between 5 and 30 nm, with an average particle size of
about 15 nm. The TOL-AgNPs (at 20 MUg/mL concentration) showed significant
antibacterial activity with significant growth inhibition of phytopathogens X.
axonopodis (22.0 +/- 0.84 mm) and P. syringae (19.5 +/- 0.66 mm). The synthesized
AgNPs had higher antibacterial activity in comparison with commercial AgNPs.
Synergistic assays with standard antibiotics revealed that nanoformulations with
tetracycline showed better broad-spectrum efficiency to control phytopathogens.
They also possessed significant antioxidant potential in terms of ABTS (IC50 =
45.6 MUg/mL), DPPH (IC50 = 56.1 MUg/mL), and NO (IC50 = 55.2 MUg/mL) free radical
scavenging activity. The TOL-AgNPs showed high cytotoxic effect against human
liver cancer cells (HepG2). Overall, dandelion-mediated AgNPs synthesis can
represent a novel approach to develop effective antimicrobial and anticancer
drugs with a cheap and eco-friendly nature.
PMID- 28699010
TI - Chemical characterization of size-segregated PM from different public transport
modes and implications of source specific contribution to public exposure.
AB - To investigate the chemical properties of particulate matter (PM) in different
public transport microenvironments in Hong Kong, the coarse (2.5-10 MUm) and fine
(<2.5 MUm) PM samples were collected in three different types of transport modes
including Mass Transit Railway (MTR)-Aboveground (AG), MTR Underground (UG), and
Bus routes from October 2013 to April 2014. Average PM2.5 concentrations through
UG, AG, and Bus routes were 47.9, 86.8, and 43.8 MUg m-3, respectively, whereas
the coarse PM concentrations were 4-5 folds less. The PM2.5 total metal
concentrations of AG route were 2.3 and 3.7 times of UG and BUS routes,
respectively, compared to those in the other two routes. The most abundant metals
at three stations in PM2.5 and coarse PM were quite similar and mainly generated
by frictional processes of wheels, rails, and brakes of the system as well as by
the mechanical wearing of these parts. The most abundant PAH in three routes in
PM2.5 was ATRQN, followed by 2-MNA, and the sum of them contributed to 35 and 42%
of total PAHs in coarse PM and PM2.5, respectively. Crude oils, lubricant oil,
diesel emissions would be the major sources of PAHs from MTR aboveground
stations. The relative abundance of the n-alkanes among different samples was
similar to the PAHs and the carbon preference index (CPI) values of the whole n
alkanes range were consistently from 0.99 to 1.04 among all samples indicating
the significant contribution from the vehicle exhaust and fossil fuel burning.
The concentrations of hopanes and steranes were higher in PM2.5 than in coarse PM
due to diesel and coal burning. These results may provide a unique opportunity to
investigate source specific contribution of the PM pollutants to the commuter
exposure in public transport.
PMID- 28699011
TI - Reflectance spectroscopy: a novel approach to better understand and monitor the
impact of air pollution on Mediterranean plants.
AB - The Mediterranean basin can be considered a hot spot not only in terms of climate
change (CC) but also for air quality. Assessing the impact of CC and air
pollution on ecosystem functions is a challenging task, and adequate monitoring
techniques are needed. This paper summarizes the present knowledge on the use of
reflectance spectroscopy for the evaluation of the effects of air pollution on
plants. First, the history of this technique is outlined. Next, we describe the
vegetation reflectance spectrum, how it can be scaled from leaf to landscape
levels, what information it contains, and how it can be exploited to understand
plant and ecosystem functions. Finally, we review the literature concerning this
topic, with special attention to Mediterranean air pollutants, showing the
increasing interest in this technique. The ability of spectroscopy to detect the
influence of air pollution on plant function of all major and minor Mediterranean
pollutants has been evaluated, and ozone and its interaction with other gases
(carbon dioxide, nitrogen oxides, and sulfur dioxide) have been the most studied.
In the recent years, novel air pollutants, such as particulate matter, nitrogen
deposition, and heavy metals, have drawn attention. Although various vegetation
types have been studied, few of these species are representative of the
Mediterranean environment. Thus, major emphasis should be placed on using
vegetation spectroscopy for better understanding and monitoring the impact of air
pollution on Mediterranean plants in the CC era.
PMID- 28699012
TI - High copper concentrations produce genotoxicity and cytotoxicity in bovine
cumulus cells.
AB - The aim of this study was to investigate the cytotoxic and genotoxic effects of
high copper (Cu) concentrations on bovine cumulus cells (CCs) cultured in vitro.
We evaluated the effect of 0, 120, 240, and 360 MUg/dL Cu added to in vitro
maturation (IVM) medium on CC viability assessed by the trypan blue (TB)
fluorescein diacetate (FDA) and 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H
tetrazolium bromide (MTT) assays, apoptosis, and DNA damage. Differences in cell
viability assessed by TB-FDA were not significant among CC treated with 0, 120,
240, and 360 MUg/dL Cu. However, mitochondrial activity assessed by MTT was lower
in CC cultured with 120, 240, and 360 MUg/dL Cu as compared with the control (p <
0.01). Percentages of apoptotic cells were higher when CCs were treated with 120,
240, and 360 MUg/dL Cu (p < 0.05) due to higher frequencies of late apoptotic
cells (p < 0.05). The frequency of live cells diminished in a dose-dependent
manner when Cu was added to the culture medium. Whereas genetic damage index
(GDI) increased significantly in CC cultured in the presence of 240 and 360
MUg/dL Cu (p ? 0.05), DNA damage increased at all Cu concentrations tested (p ?
0.05). These results indicate that Cu induces cytotoxic and genotoxic effects in
bovine CC.
PMID- 28699013
TI - Preparation of microscale zero-valent iron-fly ash-bentonite composite and
evaluation of its adsorption performance of crystal violet and methylene blue
dyes.
AB - New microscale zero-valent iron adsorbent on fly ash and bentonite matrix for
removal of crystal violet (CV) and methylene blue (MB) was synthesized through
direct reduction of iron oxide using coke and palm kernel shell. The adsorbent
was prepared as cylindrical shaped pellets to remove the CV and MB from the
aqueous solution. Nitrogen adsorption-desorption isotherm and scanning electron
microscopy (SEM) studies showed that the adsorbent is highly porous, and the iron
particles are finely dispersed on the supporting material surfaces. FTIR and UV
studies indicated that the C=C bonds in CV and C=N+(CH3)2 bonds in MB were
affected in the adsorption process. MB switched to the reduced MBH2 species while
CV was reduced to two small-size molecular compounds, explaining the higher CV
adsorption in comparison to that of MB. The reduction of these compounds was
coupled to the oxidation of Fe0 to Fe2O3 as revealed by XRD characterization of
the adsorbent after adsorption. CV and MB adsorption isotherms fitted well with
the Langmuir adsorption model. Different adsorption and reduction kinetic models
were examined for the MB and CV removal processes. A better fit of the
experimental data with the pseudo-second-order model was observed. CV and MB
adsorption increased with temperature in the 30-50 degrees C range. At 50
degrees C, adsorption capacities of CV and MB reached to 89.9 and 42.8 mg/g,
respectively. This new adsorbent showed a superior adsorption capacity for CV and
MB when compared to other adsorbents.
PMID- 28699014
TI - Predictive models for identifying the binding activity of structurally diverse
chemicals to human pregnane X receptor.
AB - Toxic chemicals entered into human body would undergo a series of metabolism,
transport and excretion, and the key roles played in there processes were
metabolizing enzymes, which was regulated by the pregnane X receptor (PXR).
However, some chemicals in environment could activate or antagonize human
pregnane X receptor, thereby leading to a disturbance of normal physiological
systems. In this study, based on a larger number of 2724 structurally diverse
chemicals, we developed qualitative classification models by the k-nearest
neighbor method. Moreover, the logarithm of 20 and 50% effective concentrations
(log EC 20 and log EC 50) was used to establish quantitative structure-activity
relationship (QSAR) models. With the classification model, two descriptors were
enough to establish acceptable models, with the sensitivity, specificity, and
accuracy being larger than 0.7, highlighting a high classification performance of
the models. With two QSAR models, the statistics parameters with the correlation
coefficient (R 2) of 0.702-0.749 and the cross-validation and external validation
coefficient (Q 2) of 0.643-0.712, this indicated that the models complied with
the criteria proposed in previous studies, i.e., R 2 > 0.6, Q 2 > 0.5. The small
root mean square error (RMSE) of 0.254-0.414 and the good consistency between
observed and predicted values proved satisfactory goodness of fit, robustness,
and predictive ability of the developed QSAR models. Additionally, the
applicability domains were characterized by the Euclidean distance-based approach
and Williams plot, and results indicated that the current models had a wide
applicability domain, which especially included a few classes of environmental
contaminant, those that were not included in the previous models.
PMID- 28699015
TI - Sponge Prokaryote Communities in Taiwanese Coral Reef and Shallow Hydrothermal
Vent Ecosystems.
AB - Previously, it was believed that the prokaryote communities of typical 'low
microbial abundance' (LMA) or 'non-symbiont harboring' sponges were merely
subsets of the prokaryote plankton community. Recent research has, however, shown
that these sponges are dominated by particular clades of Proteobacteria or
Cyanobacteria. Here, we expand on this research and assess the composition and
putative functional profiles of prokaryotic communities from LMA sponges
collected in two ecosystems (coral reef and hydrothermal vent) from vicinal
islands of Taiwan with distinct physicochemical conditions. Six sponge species
identified as Acanthella cavernosa (Bubarida), Echinodictyum asperum, Ptilocaulis
spiculifer (Axinellida), Jaspis splendens (Tetractinellida), Stylissa carteri
(Scopalinida) and Suberites sp. (Suberitida) were sampled in coral reefs in the
Penghu archipelago. One sponge species provisionally identified as Hymeniacidon
novo spec. (Suberitida) was sampled in hydrothermal vent habitat. Each sponge was
dominated by a limited set of operational taxonomic units which were similar to
sequences from organisms previously obtained from other LMA sponges. There was a
distinct bacterial community between sponges collected in coral reef and in
hydrothermal vents. The putative functional profile revealed that the prokaryote
community from sponges collected in hydrothermal vents was significantly enriched
for pathways related to DNA replication and repair.
PMID- 28699016
TI - Position-related renal perfusion disturbances as a possible underestimated
mechanism in patients with resistant hypertension: a case vignette.
AB - PURPOSE: In patients with resistant hypertension and large blood pressure
fluctuations, the role of orthostatic hypertension, associated with position
dependent renal perfusion disturbances, has not been investigated in detail yet.
METHODS: In this regard, four patients from our outpatient clinic were
investigated by the use of 24-h ambulatory blood pressure monitoring (ABPM),
active standing test, renal duplex sonography and Tc99m-mercaptoacetyltriglycine
[MAG3] renal scintigraphy in supine and upright position. RESULTS: Four patients
(three males and one female; 51-79 years) with a mean of 4.25 antihypertensive
drugs including a diuretic were evaluated. The recorded blood pressure
fluctuations were up to 89/58-198/121 mmHg. Three patients exhibited an extreme
and one a normal dipping pattern in the 24-h ABPM. Three patients demonstrated a
hypertensive orthostatic reaction in the active standing test. By duplex
sonography, a bilateral decrease in the overall intrarenal resistive indices was
shown in two patients, a unilateral overall decrease in one patient and a
localized decrease in the last patient. From a morphological standpoint of view,
all patients had a normal anatomical position and a physiologic descent of both
kidneys. But the normalized tubular extraction rate was pathologic in all
patients in the upright body position and normalized when lying down in three
patients. CONCLUSIONS: Position-dependent renal perfusion should be considered in
patients with large blood pressure fluctuations and extreme dipping. If
morphological imaging shows no abnormalities, functional imaging provides
additional information. Further investigation is needed, foremost if nephropexy
could improve blood pressure control in some of these patients.
PMID- 28699017
TI - Acceptability of HIV Self-Testing in Sub-Saharan Africa: Scoping Study.
AB - Several HIV testing models have been implemented in sub-Saharan Africa (SSA) to
improve access to HIV testing, but uptake remains poor. HIV Self-Testing (HIVST)
is now available, and may serve to overcome barriers of current testing models
which include stigma, discrimination and non-confidential testing environments. A
scoping study was conducted to provide an overview of the current literature in
SSA, as well as identify future research needs to scale-up HIVST and increase HIV
testing uptake. The outcome of the review indicated only 11 reported studies to
date, showing variable acceptability (22.3-94%) of HIVST, with acceptability of
HIVST higher among men than women in SSA. We conclude that research around HIVST
in SSA is still in its infancy, and further implementation research and
interventions are required to improve acceptability of HIVST among diverse study
populations, failing which policy adoption and scale-up may be hindered.
PMID- 28699018
TI - Polydrug Use and Heterogeneity in HIV Risk Among People Who Inject Drugs in
Estonia and Russia: A Latent Class Analysis.
AB - Non-medical drug injection is a major risk factor for HIV infection in Russia and
Estonia. Multiple drug use (polydrug) has further been associated with increased
harms. We compared HIV, injecting and sexual risk associated with polydrug use
among people who injected drugs (PWID) in 2012-2013 in Kohtla-Jarve (Estonia, n =
591) and St Petersburg (Russia, n = 811). Using latent class analysis, we
identified five (poly)drug classes, the largest consisting of single-drug
injectors among whom an opioid was the sole drug injected (56% of PWID). The four
remaining polydrug classes included polydrug-polyroute injectors who injected and
used opiates and stimulants (9%), opiate-stimulant poly-injectors who injected
amphetamine-type-stimulants with a primary opiate (7%) and opiate-opioid poly
injectors who injected opioids and opiates (16%). Non-injection stimulant co
users were injectors who also used non-injection stimulants (12%). In
multivariable multinomial regressions, all four polydrug classes were associated
with greater injection risks than single-drug injection, while opiate-stimulant
and opiate-opioid poly-injection were also associated with having multiple sex
partners. Riskier behaviours among polydrug-injectors suggest increased potential
for transmission of blood-borne and sexually-transmitted infections. In addition
to needles/syringes provision, services tailored to PWID drug and risk profiles,
could consider drug-appropriate treatment and sexual risk reduction strategies to
curb HIV transmission.
PMID- 28699019
TI - The diagnostic performance of SPECT-MPI to predict functional significant
coronary artery disease by fractional flow reserve derived from CCTA (FFRCT): sub
analysis from ACCURACY and VCT001 studies.
AB - Although single photon emission computed tomography-myocardial perfusion image
(SPECT-MPI) and fractional flow reserve (FFR) derived from coronary computed
tomographic angiography (CCTA) (FFRCT) have permitted functional assessment of
coronary artery disease (CAD), the concordance between these modalities has not
been well described. The aim of this study is to compare SPECT-MPI and anatomical
stenosis by CCTA and invasive coronary angiography to FFRCT for assessing
functional significance of CAD. We identified 62 patients with suspected CAD who
underwent >=64 slice coronary CTA and SPECT-MPI within 3 months. FFRCT was
analyzed from CCTA data using the computational fluid dynamic techniques. The
association between SPECT-MPI ischemia and FFRCT (<=0.80) was evaluated. Out of
62 patients, 186 vessels were evaluated. On a per-vessel analysis, accuracy,
sensitivity and specificity of SPECT-MPI to predict FFRCT <= 0.80 was 74.2, 45.0
and 77.7%, respectively. The area under the curve (AUC) by receiver-operating
characteristic curve analysis for SPECT-MPI demonstrated a modest performance for
predicting FFRCT <= 0.80 (AUC 0.56). Among patients with suspected CAD who were
assessed by non-invasive functional modalities, SPECT-MPI showed modest
concordance with FFRCT.
PMID- 28699020
TI - Manipulation under anaesthetic for frozen shoulder using Codman's paradox: a safe
and early return of function.
AB - PURPOSE: Although previously frozen shoulder was thought to resolve by two to
three years, recent studies demonstrated the symptoms can remain for much longer.
Manipulation under anaesthetic (MUA) has been shown to be successful in relieving
pain and restoring function. Yet, concerns have been raised regarding its safety
and the risks of complications. We utilise Codman's paradox to manipulate the
shoulder, avoiding rotational torque on the humerus. The aim of our study was to
asses shoulder function in the early post MUA period. METHODS: Two hundred twelve
consecutive patients (224 shoulders) (mean age 52.4 years) underwent MUA using
Codman's paradox for frozen shoulder as sole procedure between 2005 and 2013. All
were evaluated clinically, preoperatively and postoperatively, at three weeks and
three months, for Constant score (CS), pain, range of motion (ROM), patient
satisfaction and subjective shoulder value (SSV). RESULTS: At three weeks and
three months, a significant improvement was found in CS from 30.7 to 66 and 70
respectively. Forward elevation improved from 91 degrees to 154 degrees and 160
degrees , abduction from 69 degrees to 150 degrees and 156 degrees , internal
rotation from 12 degrees to 62 degrees and 66 degrees , and external rotation
from 10 degrees to 46 degrees and 50 degrees . Pain score improved from 4.4/15
to 9.6/15 and 10.4/15, SSV improved from 1.5/10 to 6.5/10 and 6.7/10. (p<0.001).
CONCLUSION: Use of Codman's paradox provides a safe and efficient way to perform
MUA for frozen shoulder. It results in dramatic early improvement in ROM,
functional outcomes and high satisfaction, as early as three weeks post
operatively.
PMID- 28699021
TI - Ganglion cysts of the proximal tibiofibular articulation: the role of arthrodesis
and combined partial fibula excision.
AB - PURPOSE: Cysts of the proximal tibiofibular articulation are rare and their
optimal treatment remains unclear. The objective of this study was to evaluate
the results and complications of the treatment of synovial ganglion cysts of the
proximal tibiofibular articulation by simple excision or by excision and fusion
of the proximal tibiofibular joint with a limited fibula excision. METHODS:
Between January 2005 and December 2016, seven male patients with an average age
of 46 years were treated for a ganglion cyst of the proximal tibiofibular
articulation. Nine procedures were performed in total. Four patients underwent
primary cyst excision, two underwent revision cyst excision and three underwent
revision cyst excision with arthrodesis of the proximal tibiofibular joint and
partial excision of the fibula (two patients underwent two procedures). RESULTS:
Average follow-up was 79 months. The recurrence rate was 25% for simple cyst
excision, 100% for revision cyst excision and 0% for cyst excision with
arthrodesis. Average kitaoka score was 98 for simple cyst excision and 100 for
cyst excision with arthrodesis (P = 0.34); resting visual analogue scores (VAS)
were zero in both groups. With activity VAS was 0 for simple cyst excision and
1.6 in the arthrodesis group (P = 0.33). Two of the three arthrodesis patients
went on to successful fusion. The third patient has an asymptomatic
pseudarthrosis. CONCLUSION: Simple primary cyst excision has a high failure rate
at 25%. Revision cyst excision without fusion failed in all cases. We therefore
recommend arthrodesis with limited fibula excision.
PMID- 28699022
TI - Colonization of plant roots and enhanced atrazine degradation by a strain of
Arthrobacter ureafaciens.
AB - Our previous research found that culturable atrazine degraders associated with
maize roots were dominated by genetically similar strains of Arthrobacter
ureafaciens, suggesting their rhizosphere competence. The present study aimed to
assess the root-colonizing capacity of strain A. ureafaciens DnL1-1 and to
evaluate consequent root-associated degradation of atrazine. A soil-sand assay
and pot experiments provided evidence that A. ureafaciens DnL1-1 competitively
colonized roots of maize, wheat, and alfalfa following seed inoculation. Atrazine
was not absolutely required but promoted colonization of plant roots by the
bacterium. In association with plants, A. ureafaciens DnL1-1 enhanced the
degradation of atrazine and strongly reduced accumulation of its dealkylated
metabolites. Our results show that after low-level inoculation of seeds, the
bacterium A. ureafaciens DnL1-1 can establish root populations sufficient for the
rapid degradation of atrazine in soil that makes it a promising bioremediation
agent which can be easily applied to large areas of polluted soil. Application of
the root-colonizing, atrazine-degrading Arthrobacter bacteria as seed inoculants
may be a reliable remediation strategy for soils contaminated with chlorinated s
triazines and their degradation products.
PMID- 28699023
TI - Laparoscopic uncinate process first pancreatoduodenectomy-feasibility study of a
modified 'artery first' approach to pancreatic head cancer.
AB - PURPOSE: The aim of this study was to discuss the feasibility of laparoscopic
'uncinate first' pancreatoduodenectomy. METHODS: The analysis included
prospectively collected data from 12 consecutive patients undergoing elective
pure laparoscopic 'uncinate process first' pancreatoduodenectomy (Group 1). They
were compared with patients previously operated on with a classical laparoscopic
approach (Group 2). The primary outcome was the quality of the resected specimen
(lymph node (LN) yield, R0 rate, involved resection margins). Secondary outcomes
were perioperative parameters. RESULTS: The LN yield in Group 1 was 19.3 and in
Group 2 it was 13.9 (p = 0.03). R0 resection rates did not vary (66.7 vs. 63.2%,
p = 0.84). Although the involvement of the superior mesenteric artery margin and
uncinate process margin seemed lower in Group 1, the difference was not
significant. Total operative time (467 vs. 425 min, p = 0.13) and resection time
(221 vs. 232 min, p = 0.34) were similar in both groups. The estimated blood loss
in Group 1 was 408 ml, whereas in Group 2 it was 392 ml (p = 0.33). Complication
rates were 66.7% in Group 1 and 63.2% in Group 2 (p = 0.84). Median length of
stay was 9 days in both groups (p = 0.36). Postoperative complication rates did
not differ between groups. CONCLUSIONS: Laparoscopic uncinate first approach is a
feasible method for pancreatic head neoplasms. Achieved quality of the specimen
is comparable with the traditional laparoscopic approach, whereas intra- and
postoperative course is not inferior. However, further studies on larger cohorts
are required to fully establish whether the novel approach has potential
advantages over classical access in pancreatic head cancer.
PMID- 28699024
TI - Transcriptome Sequencing Reveals Astrocytes as a Therapeutic Target in Heat
Stroke.
AB - Heat-stroke is a serious form of hyperthermia with high mortality, and can induce
severe central nervous system disorders. The neurovascular unit (NVU), which
consists of vascular cells, glial cells, and neurons, controls blood-brain
barrier (BBB) permeability and cerebral blood flow, and maintains the proper
functioning of neuronal circuits. However, the detailed function of each BBB
component in heat-stroke remains unknown. In order to interpret alterations
caused by heat stress, we performed transcriptome comparison of neuron and
astrocyte primary cultures after heat treatment. Differentially-expressed genes
were then selected and underwent Gene Ontology annotation and Kyoto Encyclopedia
of Genes and Genomes pathway analysis. Gene-act networks were also constructed,
and the expression of pivotal genes was validated by quantitative PCR, as well as
single-cell qPCR in heat-stroke rats. Our work provides valuable information on
the transcriptional changes in NVU cells after heat stress, reveals the diverse
regulatory mechanisms of two of these cellular components, and shows that a cell
type-specific approach may be a promising therapeutic strategy for heat-stroke
treatments.
PMID- 28699025
TI - Polyamines increase nitric oxide and reactive oxygen species in guard cells of
Arabidopsis thaliana during stomatal closure.
AB - A comprehensive study which was undertaken on the effect of three polyamines
(PAs) on stomatal closure was examined in relation to nitric oxide (NO) and
reactive oxygen species (ROS) levels in guard cells of Arabidopsis thaliana.
Three PAs-putrescine (Put), spermidine (Spd), and spermine (Spm)-induced stomatal
closure, while increasing the levels of NO as well as ROS in guard cells. The
roles of NO and ROS were confirmed by the reversal of closure by cPTIO (NO
scavenger) and catalase (ROS scavenger). The presence of L-NAME (NOS-like enzyme
inhibitor) reversed PA-induced stomatal closure, suggesting that NOS-like enzyme
played a significant role in NO production during stomatal closure. The reversal
of stomatal closure by diphenylene iodonium (DPI, NADPH oxidase inhibitor) or 2
bromoethylamine (BEA, copper amine oxidase inhibitor) or 1,12 diaminododecane
(DADD, polyamine oxidase inhibitor) was partial. In contrast, the presence of DPI
along with BEA/DADD reversed completely the closure by PAs. We conclude that both
NO and ROS are essential signaling components during Put-, Spd-, and Spm-induced
stomatal closure. The PA-induced ROS production is mediated by both NADPH oxidase
and amine oxidase. The rise in ROS appears to be upstream of NO. Ours is the
first detailed study on the role of NO and its dependence on ROS during stomatal
closure by three major PAs.
PMID- 28699026
TI - Aminolevulinic acid and nitric oxide regulate oxidative defense and secondary
metabolisms in canola (Brassica napus L.) under drought stress.
AB - To minimize the damaging effects of stresses, plant growth regulators (PGRs) are
widely used to sustain the plant life under stress-prone environments. So, a
study was carried out to evaluate the response of two canola (Brassica napus L.)
cultivars, Dunkeld and Cyclone, to foliar-applied two potential PGRs, nitric
oxide (NO) and 5-aminolevulinic acid, under water deficit conditions. In this
study, the levels of NO and ALA used were 0.02 and 0.895 mM, respectively. Plants
of both canola cultivars were subjected to control (100% field capacity) and
water deficit (60% field capacity). Drought stress significantly decreased
growth, chlorophyll pigments, relative water contents (RWC), and soluble
proteins, while it increased relative membrane permeability (RMP), proline,
glycinebetaine (GB), malondialdehyde (MDA), total phenolics, and activities of
catalase (CAT) and peroxidase (POD) enzymes in both cultivars. Foliar application
of PGRs improved growth, chlorophyll a, GB, total phenolics, CAT activity, and
total soluble proteins, while it decreased RMP, MDA, and POD activity in both
canola cultivars. Other physio-biochemical attributes such as chlorophyll b, RWC,
hydrogen peroxide (H2O2) and proline contents as well as superoxide dismutase
(SOD) activity remained unaffected due to application of PGRs. So, the results of
the present study suggest that exogenous application of NO and ALA could be
useful to enhance the drought tolerance of canola plants by up-regulating the
oxidative defense system, osmoprotectant accumulation, and minimizing the lipid
peroxidation.
PMID- 28699027
TI - Erratum to: Increased glutamic acid decarboxylase expression in the hypothalamic
suprachiasmatic nucleus in depression.
PMID- 28699028
TI - The occipital face area is causally involved in the formation of identity
specific face representations.
AB - Transcranial magnetic stimulation (TMS) and neuroimaging studies suggest a role
of the right occipital face area (rOFA) in early facial feature processing.
However, the degree to which rOFA is necessary for the encoding of facial
identity has been less clear. Here we used a state-dependent TMS paradigm, where
stimulation preferentially facilitates attributes encoded by less active neural
populations, to investigate the role of the rOFA in face perception and
specifically in image-independent identity processing. Participants performed a
familiarity decision task for famous and unknown target faces, preceded by brief
(200 ms) or longer (3500 ms) exposures to primes which were either an image of a
different identity (DiffID), another image of the same identity (SameID), the
same image (SameIMG), or a Fourier-randomized noise pattern (NOISE) while either
the rOFA or the vertex as control was stimulated by single-pulse TMS. Strikingly,
TMS to the rOFA eliminated the advantage of SameID over DiffID condition, thereby
disrupting identity-specific priming, while leaving image-specific priming
(better performance for SameIMG vs. SameID) unaffected. Our results suggest that
the role of rOFA is not limited to low-level feature processing, and emphasize
its role in image-independent facial identity processing and the formation of
identity-specific memory traces.
PMID- 28699029
TI - Access to Pharmacotherapy Amongst Women with Bipolar Disorder during Pregnancy: a
Preliminary Study.
AB - Bipolar disorder among pregnant women has deleterious effects on birth and child
outcomes and is currently under-detected, not addressed effectively, or
exacerbated through inappropriate treatment. The goal of this study was to
identify perspectives of pregnant and postpartum women with bipolar disorder on
barriers and facilitators to psychiatric treatment during pregnancy. In-depth
interviews were conducted with pregnant and postpartum women who scored >= 10 on
the Edinburgh Postnatal Depression Scale and met DSM-IV criteria for bipolar
disorder I, II or not otherwise specified using the Mini International
Neuropsychiatric Interview version 5.0. Interviews were transcribed, and
resulting data were analyzed using a grounded theory approach to identify
barriers and facilitators to bipolar disorder treatment access in pregnancy.
Participant identified barriers included perception that psychiatric providers
lack training and experience in the treatment of psychiatric illness during
pregnancy, are reluctant to treat bipolar disorder among pregnant women, and
believe that pharmacotherapy is not needed for psychiatric illness during
pregnancy. Facilitators included participants' perception that providers'
acknowledge risks associated with untreated or undertreated psychiatric illness
during pregnancy and provide psycho-education about the risks, benefits and
alternatives to pharmacotherapy. Psychiatric providers are critically important
to the treatment of bipolar disorder and need knowledge and skills necessary to
provide care during the perinatal period. Advancing psychiatric providers'
knowledge/skills may improve access to pharmacotherapy for pregnant women with
bipolar disorder.
PMID- 28699030
TI - DNA damage response and disorders with hematology, oncology and immunology.
PMID- 28699031
TI - Effectiveness and nephrotoxicity of a 2-year medium dose of cyclosporine in
pediatric patients with steroid-dependent nephrotic syndrome: determination of
the need for follow-up kidney biopsy.
AB - BACKGROUND: High dose of cyclosporine (CyA) for >=2 years in children with
steroid-dependent nephrotic syndrome (SDNS) increases the risk for nephropathy.
Considering this, risk can be lowered with lower doses of CyA; we evaluated the
effects of a medium dose of CyA, with target serum level, C2, of 450 ng/ml, over
a 2-year period of observation, to determine the need for follow-up kidney
biopsy. METHODS: We retrospectively evaluated C2 levels in 38 patients (17 males,
5.2 +/- 2.9 years old) with SDNS at treatment initiation, at 6, 12 and 18 months
during treatment, and at the time of kidney biopsy, 2-year after treatment
initiation. Fifteen patients were also treated with mizoribine or mycophenolate
mofetil. A number of relapses-per-patient-per-year, relative to SDNS onset and
initiation of CyA treatment, were evaluated. Serum levels of total protein,
albumin and total cholesterol, blood urea nitrogen level, and the estimated
glomerular filtration rate were measured at treatment initiation and at 1- and 2
year post-treatment initiation. RESULTS: Only one very mild case of CyA
associated nephrotoxicity was identified based on biopsy results at 2-year post
treatment initiation. C2 concentrations were maintained at 422.2 +/- 133.5 ng/ml
and the number of relapses decreased from 3.0 relapses-per-patient-per-year prior
to CyA treatment to 0.47 relapses-per-patient-per-year after CyA treatment. No
effects of the treatment on the estimated glomerular filtration rate were noted.
CONCLUSION: A 2-year treatment with a medium dose of cyclosporine A with or
without other immunosuppressive agents is relatively safe with regard to the
development of cyclosporine A nephrotoxicity.
PMID- 28699032
TI - Combined cyclosporine and prednisolone therapy using cyclosporine blood
concentration monitoring for adult patients with new-onset minimal change
nephrotic syndrome: a single-center pilot randomized trial.
AB - BACKGROUND: Minimal change nephrotic syndrome (MCNS) responds well to steroids,
but some patients show frequent relapses. Long-term steroid administration leads
to various adverse effects. We previously reported the effectiveness in
refractory nephrosis patients of administrating microemulsified CyA (ME-CyA) once
before meals and setting the target value of the CyA blood concentration at 2 h
after ME-CyA administration (C2) to 600-1200 ng/ml. On this trial we evaluate the
effectiveness and safety of ME-CyA for suppressing relapse of adult new-onset
MCNS patients using C2 monitoring. METHODS: Adult new-onset MCNS patients were
randomly allocated to a ME-CyA + prednisolone group ("CyA + PSL") (n = 11) and a
PSL-alone group ("PSL-alone") (n = 10). The drug administration period was 18
months followed by an observation period of 12 months. RESULTS: The duration of
remission tended to be longer in CyA + PSL with C2 >600 ng/ml than in PSL-alone
(P = 0.112). The relapse rate up to 18 months was significantly lower in CyA +
PSL with C2 >600 ng/ml than in PSL-alone (P = 0.02). C2 was significantly higher
in the patients with no relapse at 18 months than that in the patients with
relapse (P = 0.048). In CyA + PSL, the total dose of PSL was significantly
reduced compared with PSL-alone (P = 0.002). Cosmetic adverse effects tended to
be fewer in CyA + PSL. CONCLUSIONS: The combination treatment regimen of ME-CyA
and PSL with C2 >600 ng/ml has potential to be an important treatment option for
adult new-onset MCNS patients. However, after ME-CyA dosage reduction and
discontinuation, the relapse rate increased. It is thus necessary to establish a
better dose-reduction method.
PMID- 28699033
TI - Low white blood cell count is independently associated with chronic kidney
disease progression in the elderly: the CKD-ROUTE study.
AB - BACKGROUND: Elevated white blood cell (WBC) count is a well-known predictor of
chronic kidney disease (CKD) progression. However, elderly patients commonly fail
to develop a high WBC count in response to several diseased states and may
instead present a low WBC count. Therefore, we hypothesized that low WBC count,
in addition to high WBC count, is associated with CKD progression in the elderly.
METHODS: We conducted a prospective cohort study using 3-year follow-up data from
the CKD Research of Outcomes in Treatment and Epidemiology study. In the present
study, participants aged over 60 years with pre-dialysis CKD stages G2-G5 were
eligible. Patients were stratified into three groups according to WBC count using
tertiles (T). The primary outcome was a composite of end-stage renal disease and
a 50% reduction in estimated glomerular filtration rate. Data were analyzed using
Cox proportional hazard models with adjustments for covariates. RESULTS: We
enrolled 697 patients (males, 69%). The median WBC count was 6100 cells/ul (T1,
<5400, n = 222; T2, 5400-6900, n = 235; T3, >=6900, n = 240). During a median
follow-up of 868 days, the primary outcome was observed in 170 patients, whereas
54 patients died. T1 and T3 had significantly higher hazard ratios (HR) than T2
(T1, HR 1.69, 95% confidence interval 1.14-2.51; T3, HR 1.63, 95% confidence
interval 1.10-2.41). Moreover, T1 had a significantly higher adjusted HR (1.54,
95% confidence interval 1.00-2.37). CONCLUSION: Low WBC count is independently
associated with CKD progression in the elderly.
PMID- 28699034
TI - [Definition of R1 resection in thyroid carcinoma].
AB - BACKGROUND: The residual tumor (R) classification describes the tumor status
after therapy, which in patients with thyroid carcinomas is predominantly after
surgical treatment. The aim of the R classification is to indicate the success of
(surgical) therapy, which can influence further therapeutic procedures and allow
relevant prognostic statements. OBJECTIVE: Definition of R1 resection as well as
minimally invasive extrathyroidal growth of thyroid carcinomas as the latter is a
common prerequisite for R1 resected thyroid carcinoma. RESULTS: Presentation of
the pathological work-up and histopathological assessment. Proposal to supplement
and extend the recently introduced 8th edition of the TNM classification in order
to systematically classify minimally invasive extrathyroidal carcinomas.
CONCLUSION: The presented definitions (e.g. R1, minimally invasive extrathyroidal
invasion) in combination with the proposed extension of the TNM classification
permit the prospective scientific assessment of the biological relevance of these
two parameters.
PMID- 28699035
TI - eHealth literacy, Internet and eHealth service usage: a survey among cancer
patients and their relatives.
AB - PURPOSE: The aim of our study was to investigate Internet and eHealth usage, with
respect to eHealth literacy, by cancer patients and their relatives. PATIENTS AND
METHODS: Using a standardized questionnaire we asked patients who attended
lectures on complementary medicine in 2016. RESULTS: We received 142
questionnaires. The frequency of general Internet usage was directly associated
with younger age and better Internet connection. Younger participants were not
only more confident in allocating health-related Internet information into
reliable or unreliable facts, but also more confident and capable of gaining
medical knowledge through eHealth services. A regular use of eHealth services
facilitated the decision-making process. Reading ability was associated with a
better understanding regarding eHealth offers. CONCLUSION: In a modern health
care system, emphasis should be on skills contributing to eHealth literacy among
patients to improve their ability to profit from eHealth offers and improve
health care.
PMID- 28699036
TI - Spatiotemporal expression of a twist homolog in the leech Helobdella austinensis.
AB - Genes of the twist family encode bHLH transcription factors known to be involved
in the regulation and differentiation of early mesoderm. Here, we report our
characterization of Hau-twist, a twist homolog from the leech Helobdella
austinensis, a tractable lophotrochozoan representative. Hau-twist was expressed
in segmental founder cells of the mesodermal lineage, in subsets of cells within
the mesodermal lineage of the germinal plate, in circumferential muscle fibers of
a provisional integument during segmentation and organogenesis stages and on the
ventral side of the developing proboscis. Thus, consistent with other systems,
our results suggest that twist gene of the leech Helobdella might function in
mesoderm differentiation.
PMID- 28699037
TI - Erratum to: Acute ocular traumatic imaging: what the radiologist should know.
PMID- 28699038
TI - [Subjective patient satisfaction after nasal septumplasty].
AB - BACKGROUND: Septal surgery (SP) is one of the most frequently performed
operations in Germany and thus represents a high cost burden for the health
system. However, sufficient data on postoperative patient satisfaction and
objective indication criteria for surgery are still lacking. OBJECTIVE: This
study aimed to determine postoperative patient satisfaction and possible factors
influencing the subjective success of SP, in order to optimize preoperative
indication establishment. MATERIALS AND METHODS: A total of 600 questionnaires
were sent by mail, resulting in inclusion of 238 patients (60 female, 178 male)
who had received SP. The questionnaires were retrospectively evaluated using
validated questionnaires (NOSE-D, SNOT-20-GAV) as well as a self-designed
questionnaire regarding patients' subjective satisfaction after SP. Clinical data
were collected from the electronic patient record. RESULTS: Follow-up was between
2 and 11 years. The main symptom for SP was difficult nasal breathing in 89% (212
of 238) of patients. In total, 68% (161) were satisfied with the outcome of
surgery and 73% (172) of the patients would opt for SP again. The scores of the
visual analog scales for nasal breathing, smell, nasal secretion, physical
performance, use of nose drops, and headache were statistically significantly
improved postoperatively. Additionally, the analysis of Nose-D and SNOT-20-GAV
questionnaires presented a significant improvement in scores. Surprisingly,
patients with a prolonged duration of septal splints were more satisfied.
Previous nasal surgery had no significant influence. CONCLUSION: SP leads to a
high degree of patient satisfaction, if the indication for surgery is correct.
The main complaint of patients should be "difficult" nasal breathing. SP leads to
a significant improvement in preoperative symptoms.
PMID- 28699039
TI - [Prophylaxis of venous thromboembolic events in head and neck surgery].
AB - BACKGROUND: Application of perioperative thrombosis prophylaxis in head and neck
surgery lacks consistent standards in Germany. Due to sparse data, the latest
German S3 guideline concerning prophylaxis of thromboembolic events recommends a
restrictive handling of anticoagulants in head and neck surgery, with few
specific recommendations. OBJECTIVE: The aim of this paper is to provide concrete
clinical recommendations based on a systematic literature review and the S3
guidelines. MATERIALS AND METHODS: A keyword-based literature search was
performed and the German S3 guideline "Prophylaxis of Venous Thromboembolic
Events" was used to state the current level of evidence and provide a clinical
algorithm. RESULTS: Eight additional cohort studies dealing with the incidence of
thromboembolic events in head and neck surgery were identified. There were no
randomized controlled trials. In the proposed algorithm, a classification of
dispositional (patient history) and expositional (operation time) risk into three
groups enables preoperative risk evaluation indicating the individual demand for
prophylaxis. In short operations without major tissue traumatization, routine
drug-based thrombosis prophylaxis is not necessary, provided no third-grade risk
factors (earlier thromboembolic event, coagulopathy, or malignant disease) are
present. Low molecular weight heparins should be used as anticoagulants for drug
based prophylaxis. CONCLUSION: Prophylaxis of thromboembolic events in head and
neck surgery is of high clinical relevance but there is currently limited
evidence regarding its implementation. This paper is based on a systematic
literature review and provides a clinical algorithm for head and neck surgeons.
PMID- 28699040
TI - [Neuroprotective medication in vestibular schwannoma surgery].
AB - BACKGROUND: Except for glucocorticoids there is a lack of neuroprotective
medication in neurosurgical interventions. OBJECTIVE: An overview of clinical
trials investigating administration of the calcium antagonist nimodipine and
hydroxyethyl starch (HES) in vestibular schwannoma (VS) surgery is given. Basic
research is addressed and potential neuroprotective effect mechanisms are
discussed, as are perspectives for application of the concept to other types of
surgery with a risk postoperative impairment of nerve function. MATERIALS AND
METHODS: A selective PubMed search was performed and all 10 clinical trials
corresponding to the search criteria were included. RESULTS: Four trials with an
intraoperative start of the medication showed a positive effect for the
preservation of facial nerve function and hearing preservation. A pilot study
showed superiority of prophylactic treatment over intraoperative application.
There were no significant results in a prospective multicenter phase III trial.
After 1 year, postoperative facial nerve preservation rates were excellent in
both groups. However, the risk of hearing loss was twice as high in the control
group. A combined analysis of the phase III trial with its pilot study showed
significant results for better hearing preservation rates in the treatment group
(probably by increasing the case load). CONCLUSION: Prophylactic nimodipine can
be recommended in VS surgery in patients with good preoperative hearing. The
effect mechanisms of nimodipine and modifications to prophylaxis should be
clarified in basic research.
PMID- 28699041
TI - Pulse Rate and Transit Time Analysis to Predict Hypotension Events After Spinal
Anesthesia During Programmed Cesarean Labor.
AB - Prophylactic treatment has been proved to reduce hypotension incidence after
spinal anesthesia during cesarean labor. However, the use of pharmacological
prophylaxis could carry out undesirable side-effects on mother and fetus. Thus,
the prediction of hypotension becomes an important challenge. Hypotension events
are hypothesized to be related to a malfunctioning of autonomic nervous system
(ANS) regulation of blood pressure. In this work, ANS responses to positional
changes of 51 pregnant women programmed for a cesarean labor were explored for
hypotension prediction. Lateral and supine decubitus, and sitting position were
considered while electrocardiographic and pulse photoplethysmographic signals
were recorded. Features based on heart rate variability, pulse rate variability
(PRV) and pulse transit time (PTT) analysis were used in a logistic regression
classifier. The results showed that PRV irregularity changes, assessed by
approximate entropy, from supine to lateral decubitus, and standard deviation of
PTT in supine decubitus were found as the combination of features that achieved
the best classification results sensitivity of 76%, specificity of 70% and
accuracy of 72%, being normotensive the positive class. Peripheral regulation and
blood pressure changes, measured by PRV and PTT analysis, could help to predict
hypotension events reducing prophylactic side-effects in the low-risk population.
PMID- 28699042
TI - Is the non-sentinel lymph node compartment the next site for melanoma progression
from the sentinel lymph node compartment in the regional nodal basin?
AB - Melanoma patients with additional positive lymph nodes in the completion lymph
node dissection (CLND) following a positive sentinel lymph node (SLN) biopsy
would have a poorer prognosis than patients with no additional positive lymph
nodes. We hypothesize that the progression of disease from the SLN to the non-SLN
compartment is orderly and is associated with the worsening of the disease
status. Thus, the SLN and non-SLN compartments are biologically different in that
cancer cells, in general, arrive in the SLN compartment before spreading to the
non-SLN compartment. To validate this concept, we used a large cohort of melanoma
patients from our prospective SLN database in an academic tertiary medical
center. Adult cutaneous melanoma patients (n = 291) undergoing CLND after a
positive SLN biopsy from 1994 to 2009 were analyzed. Comparison of 5-year disease
free survival and 5-year overall survival between positive (n = 66) and negative
(n = 225) CLND groups was made. The 5-year disease-free survival rates were 55%
(95% CI 49-62%) for patients with no additional LN on CLND versus 14% (95% CI 8
26%) in patients with positive LN on CLND (p < 0.0001, log-rank test). The median
disease-free survival time was 7.4 years with negative CLND (95% CI 4.4-15+
years) and 1.2 years with positive CLND (95% CI 1.0-1.8 years). The 5-year
overall survival rates were 67% (95% CI 61-74%) for negative CLND versus 38% (95%
CI 28-52%) for positive CLND (p < 0.0001, log-rank test). The median overall
survival time was 12.1 years for negative CLND (95% CI 9.3-15+ years) and 2.5
years for positive CLND (95% CI 2.2-5.7 years). This study shows that CLND status
is a significant prognostic factor for patients with positive SLNs undergoing
CLND. Also, it suggests an orderly progression of metastasis from the SLN to the
non-SLN compartment. Thus, the SLN in the regional nodal basin draining the
primary melanoma may serve as an important gateway for metastasis to the non-SLN
compartment and beyond to the systemic sites.
PMID- 28699043
TI - Noninvasive assessment of cutaneous alterations in mice exposed to whole body
gamma irradiation using optical imaging techniques.
AB - We report the results of a study carried out to investigate the potential of
optical techniques such as optical coherence tomography, Mueller matrix
spectroscopy, and cross-polarization imaging for noninvasive monitoring of the
ionizing radiation exposure-induced alterations in cutaneous tissue of mice.
Radiation dose-dependent changes were observed in tissue microvasculature and
tissue optical parameters like retardance and depolarization as early as 1 h post
radiation exposure. Results suggest that these optical techniques may allow early
detection of radiation dose-dependent alterations which could help in screening
of population exposed to radiation.
PMID- 28699044
TI - UVA1 vs. narrowband UVB phototherapy in the treatment of palmoplantar pustulosis:
a pilot randomized controlled study.
AB - UVA1 phototherapy, a new therapeutic approach, has recently been shown good
efficacy in the treatment of palmoplantar pustulosis (PPP). The purpose of this
study was to compare the efficacy of UVA1 and narrowband UVB (NB-UVB) therapy in
the treatment of PPP. Patients with PPP were randomly assigned to either UVA1 or
NB-UVB therapy according to a left-right randomization table. Both treatments
were performed three times weekly for up to 30 sessions. Clinical evaluation was
based on the Palmoplantar Pustular Psoriasis Area and Severity Index (PPPASI)
score. Totally 64 patients completed the study. Both UVA1 and NB-UVB therapy
showed a statistically significant reduction of PPPASI score compared with the
baseline value at the end of the treatment period (P < 0.05). There was a
significantly greater mean reduction of PPPASI score in the UVA1 treated group
when compared to the NB-UVB treated patients at 30 sessions (6.0 +/- 2.4 vs. 4.4
+/- 1.4, P < 0.05). No phototoxic reaction or bullous changes were observed in
either group. Both NB-UVB and UVA1 phototherapy of PPP resulted in significant
improvement. UVA1 phototherapy was more effective than NB-UVB irradiation in the
treatment of PPP.
PMID- 28699045
TI - Effectiveness of Nutrition Intervention in a Selected Group of Overweight and
Obese African-American Preschoolers.
AB - High prevalence of childhood obesity persists as a public health concern in the
USA. However, limited study has been conducted on the effectiveness of nutrition
education focused on African-American (AA) preschoolers (PSLRs) in the preschool
settings. The aim of this pilot study was to explore the effectiveness of
nutrition education on AA PSLR's health. A convenience sample of 164 PSLRs (95%
AA, 44% female) from six Head Start (HS) centers in a Midwestern metropolitan
area was randomly assigned to 3 groups: intervention group A, standard curriculum
plus nutrition education for PSLRs; intervention group B, standard curriculum
plus nutrition education for PSLRs and their caregivers (CGs); and control group,
standard curriculum. Baseline and post-intervention differences within each group
and differences among the three groups in body mass index (BMI) percentiles,
blood lipid profile, and food preference/knowledge were analyzed. No significant
changes in BMI percentiles among the three groups were observed. When only
overweight and obese PSLRs were considered, there was a significant reduction in
BMI percentile in group B (PSLR + CG) and control group. More PSLRs in all three
groups had blood lipid levels in the acceptable with few in the high-risk levels.
There were no changes in nutrition knowledge and healthy eating behavior post
intervention. This pilot study supports including both PSLRs and CGs in future
preschool-based interventions and the need for more intense intervention to
optimize healthy outcomes, especially for those AA PSLRs who are overweight or
obese.
PMID- 28699047
TI - Titrating droxidopa to maximize symptomatic benefit in a patient with Parkinson
disease and neurogenic orthostatic hypotension.
PMID- 28699046
TI - Optical clearing and fluorescence deep-tissue imaging for 3D quantitative
analysis of the brain tumor microenvironment.
AB - BACKGROUND: Three-dimensional visualization of the brain vasculature and its
interactions with surrounding cells may shed light on diseases where aberrant
microvascular organization is involved, including glioblastoma (GBM). Intravital
confocal imaging allows 3D visualization of microvascular structures and
migration of cells in the brain of mice, however, with limited imaging depth. To
enable comprehensive analysis of GBM and the brain microenvironment, in-depth 3D
imaging methods are needed. Here, we employed methods for optical tissue clearing
prior to 3D microscopy to visualize the brain microvasculature and routes of
invasion of GBM cells. METHODS: We present a workflow for ex vivo imaging of
optically cleared brain tumor tissues and subsequent computational modeling. This
workflow was used for quantification of the microvasculature in relation to
nuclear or cellular density in healthy mouse brain tissues and in human
orthotopic, infiltrative GBM8 and E98 glioblastoma models. RESULTS: Ex vivo
cleared mouse brain tissues had a >10-fold imaging depth as compared to
intravital imaging of mouse brain in vivo. Imaging of optically cleared brain
tissue allowed quantification of the 3D microvascular characteristics in healthy
mouse brains and in tissues with diffuse, infiltrative growing GBM8 brain tumors.
Detailed 3D visualization revealed the organization of tumor cells relative to
the vasculature, in both gray matter and white matter regions, and patterns of
multicellular GBM networks collectively invading the brain parenchyma.
CONCLUSIONS: Optical tissue clearing opens new avenues for combined quantitative
and 3D microscopic analysis of the topographical relationship between GBM cells
and their microenvironment.
PMID- 28699048
TI - Managing neurogenic orthostatic hypotension in a patient presenting with pure
autonomic failure who later developed Parkinson disease.
PMID- 28699049
TI - The target of vasovagal syncope is hemostasis and not heart protection.
PMID- 28699050
TI - [Optic nerve hypoplasia and septo-optic dysplasia].
AB - Optic nerve hypoplasia (ONH) is one of the most common causes of congenital
visual impairment. It was first described in 1915 and represents a developmental
disorder of the central nervous system. It is often associated with intracranial
midline defects and is then referred to as septo-optic dysplasia (SOD). The
symptoms of ONH range from minimal visual dysfunction to significant visual
impairment with sensory defect nystagmus and even blindness. The ONH is often
associated with further systemic, endocrinological and neurological abnormalities
requiring a close interdisciplinary treatment of the patients.
PMID- 28699051
TI - [Assessing the added benefit of new ophthalmic drugs : Which additional insights
can be extracted from the early benefit assessment?]
AB - Until now six ophthalmic agents have undergone the German early benefit
assessment according to S 35a Social Security Code (SGB) V in a total of eleven
indications. Only one agent (ocriplasmin) was recognized by the Federal Joint
Committee as having an added benefit based on submitted study data for a
subpopulation (indication of a considerable added benefit, limited for 5 years)
and another agent, idebenone, received an added benefit due to its orphan drug
designation (proof of a not quantifiable added benefit, limited for 2 years). All
remaining agents (aflibercept, bromfenac, nepafenac and tafluprost/timolol) were
not recognized as having an added benefit. The analysis showed that there was a
lack of suitable evidence. Some reasons for the inappropriateness of the
conducted trials for the usage in the early benefit assessment are the
comparative therapy, the patient population included or the dosage regimens. For
two agents (bromfenac and nepafenac) the pharmaceutical company did not even
submit a value dossier. The examples from ophthalmology illustrate the
methodological and procedural shortcomings of the assessment process and that
results of an early benefit assessment should be interpreted with caution.
PMID- 28699052
TI - Young Adults on the Autism Spectrum at College: Successes and Stumbling Blocks.
AB - There is limited information on outcomes for young adults with autism spectrum
disorder (ASD), including achievement at college. Qualitative interviews were
conducted with 18 families reporting a degree-seeking college experience for
their young adult with ASD. Interview transcripts were analyzed using a grounded
theory approach. Four themes surrounding success and failure at college emerged.
Preparation Beyond Academics involved challenges associated with ASD, such as
social, executive functioning, and mental health issues, and to what extent these
had been addressed prior to leaving high school. Student/College Fit related to
whether a student's capabilities were matched to college location, size, and
culture, while Campus Supports and Family Supports concerned assistance provided
by colleges and families, respectively. Implications for future practice are
discussed.
PMID- 28699053
TI - Vicarious Effort-Based Decision-Making in Autism Spectrum Disorders.
AB - This study investigated vicarious effort-based decision-making in 50 adolescents
with autism spectrum disorders (ASD) compared to 32 controls using the Effort
Expenditure for Rewards Task. Participants made choices to win money for
themselves or for another person. When choosing for themselves, the ASD group
exhibited relatively similar patterns of effort-based decision-making across
reward parameters. However, when choosing for another person, the ASD group
demonstrated relatively decreased sensitivity to reward magnitude, particularly
in the high magnitude condition. Finally, patterns of responding in the ASD group
were related to individual differences in consummatory pleasure capacity. These
findings indicate atypical vicarious effort-based decision-making in ASD and more
broadly add to the growing body of literature addressing social reward processing
deficits in ASD.
PMID- 28699054
TI - The Development of an Internet-Based Treatment for Problem Gamblers and Concerned
Significant Others: A Pilot Randomized Controlled Trial.
AB - Problem gambling creates significant harm for the gambler and for concerned
significant others (CSOs). While several studies have investigated the effects of
individual cognitive behavioral therapy (CBT) for problem gambling, less is known
about the effects of involving CSOs in treatment. Behavioral couples therapy
(BCT) has shown promising results when working with substance use disorders by
involving both the user and a CSO. This pilot study investigated BCT for problem
gambling, as well as the feasibility of performing a larger scale randomized
controlled trial. 36 participants, 18 gamblers and 18 CSOs, were randomized to
either BCT or individual CBT for the gambler. Both interventions were Internet
delivered self-help interventions with therapist support. Both groups of gamblers
improved on all outcome measures, but there were no differences between the
groups. The CSOs in the BCT group lowered their scores on anxiety and depression
more than the CSOs of those randomized to the individual CBT group did. The
implications of the results and the feasibility of the trial are discussed.
PMID- 28699055
TI - Recovery of heart rate variability after treadmill exercise analyzed by lagged
Poincare plot and spectral characteristics.
AB - The aim of this study was to analyze the recovery of heart rate variability (HRV)
after treadmill exercise and to investigate the autonomic nervous system response
after exercise. Frequency domain indices, i.e., LF(ms2), HF(ms2), LF(n.u.),
HF(n.u.) and LF/HF, and lagged Poincare plot width (SD1 m ) and length (SD2 m )
were introduced for comparison between the baseline period (Pre-E) before
treadmill running and two periods after treadmill running (Post-E1 and Post-E2).
The correlations between lagged Poincare plot indices and frequency domain
indices were applied to reveal the long-range correlation between linear and
nonlinear indices during the recovery of HRV. The results suggested entirely
attenuated autonomic nervous activity to the heart following the treadmill
exercise. After the treadmill running, the sympathetic nerves achieved dominance
and the parasympathetic activity was suppressed, which lasted for more than 4
min. The correlation coefficients between lagged Poincare plot indices and
spectral power indices could separate not only Pre-E and two sessions after the
treadmill running, but also the two sessions in recovery periods, i.e., Post-E1
and Post-E2. Lagged Poincare plot as an innovative nonlinear method showed a
better performance over linear frequency domain analysis and conventional
nonlinear Poincare plot.
PMID- 28699056
TI - Killing Activity of Micafungin Against Candida albicans, C. dubliniensis and
Candida africana in the Presence of Human Serum.
AB - We compared killing activity of micafungin in time-kill experiments in RPMI-1640
with and without 50% serum against Candida albicans, Candida dubliniensis and
Candida africana reference strains and clinical isolates. Killing rates (k
values) were determined for each strain and concentration. In RPMI-1640 MIC
ranges were 0.015-0.03, 0.015-0.03 and 0.015 mg/L against C. albicans, C.
dubliniensis and C. africana, respectively. In 50% serum MIC values for the three
species increased 16- to 64-fold. In RPMI-1640 micafungin was fungicidal against
two of three C. albicans isolates at 16 and 32 mg/L within 14.54 h and
fungistatic against all C. africana and C. dubliniensis. Fifty per cent serum
significantly decreased the growth rate of C. africana, but not of the other two
species; weak in vivo replication ability of C. africana was confirmed in murine
model. In 50% serum micafungin at 0.25 and 1 mg/L did not inhibit any of the
three species (k values were always negative). Micafungin killing rate in 50%
serum at 4, 16 and 32 mg/L was significantly decreased for C. albicans, but
increased for C. dubliniensis compared to RPMI-1640. Killing activity of
micafungin against C. africana was comparable or higher in 50% serum than in RPMI
1640. Although micafungin is a highly protein-bound drug, it was equally
effective against the species of the C. albicans complex in 50% serum at
therapeutic trough concentration (4 mg/L). Both in vitro and in vivo data
confirmed the low virulence of C. africana compared to the two sibling species.
PMID- 28699058
TI - Frustrated Patients and Fearful Physicians.
PMID- 28699057
TI - The Role of Lipid Bodies in the Microglial Aging Process and Related Diseases.
AB - Lipid bodies (LBs) have long been considered to be organelles merely for the
storage of neutral lipids. However, recent studies have shown the significance of
LBs in signal transduction, especially in glial cells, including microglia.
Microglial cells are the resident mononuclear phagocytes in the central nervous
system and have a close relationship with the aging process and neurodegenerative
diseases. Evidence suggests that LBs accumulate and are remodeled during the
aging process and the development of neuroinflammatory conditions. However, the
mechanisms underlying the formation of LBs under these conditions and the
mechanism by which LB remodeling influences the progression of neurodegeneration
remain to be clarified. In this review, we have summarized the findings from
recent studies with the aim of further elucidating these issues.
PMID- 28699059
TI - Who Gets Testosterone? Patient Characteristics Associated with Testosterone
Prescribing in the Veteran Affairs System: A Cross-Sectional Study.
PMID- 28699060
TI - Assessing the Burden of Treatment.
AB - Current healthcare systems and guidelines are not designed to adapt to care for
the large and growing number of patients with complex care needs and those with
multimorbidity. Minimally disruptive medicine (MDM) is an approach to providing
care for complex patients that advances patients' goals in health and life while
minimizing the burden of treatment. Measures of treatment burden assess the
impact of healthcare workload on patient function and well-being. At least two of
these measures are now available for use with patients living with chronic
conditions. Here, we describe these measures and how they can be useful for
clinicians, researchers, managers, and policymakers. Their work to improve the
care of high-cost, high-use, complex patients using innovative patient-centered
models such as MDM should be supported by periodic large-scale assessments of
treatment burden.
PMID- 28699061
TI - Hydroxypropyl methylcellulose 2% for dry eye prevention during
phacoemulsification in senile and diabetic patients.
AB - PURPOSE: To assess the effect of hydroxypropyl methylcellulose (HPMC) 2% to
prevent dry eye during phacoemulsification in senile and diabetic patients.
METHODS: This prospective interventional case series comprised 60 eyes (44
patients) with age-related cataract scheduled for standardized
phacoemulsification surgery. The patients were assigned to receive either
balanced saline solution (BSS, 30 eyes) or HPMC 2% (30 eyes) during surgery.
Preoperative and postoperative examinations (1, 3, 7 and 30 days) included
measurements of automatic noninvasive tear film breakup time (NITBUT),
fluorescein staining, Schirmer I test, tear meniscus height, depth and area and
subjective symptoms. Intraoperative application frequency was also assessed.
RESULTS: The mean age of patients was 68.7 +/- 2.3 years. The application
frequency of BSS during surgery was significantly reduced in HPMC group (P =
0.001). The incidence of dry eye syndrome (DES) was significantly reduced in HPMC
group in both senile and diabetic patients. Scores of subjective symptoms were
significantly higher in the BSS group in 1 day (P = 0.003) and 3 days (P = 0.043)
postoperatively. The first and average NITBUT were significantly higher in HPMC
group in 1 day and 3 days after surgery, respectively (P = 0.012 and P = 0.024,
respectively). NITBUT values did not significantly change postoperatively in the
HPMC group (P > 0.05), while they were significantly lower postoperatively in the
BSS group. CONCLUSIONS: Application of HPMC 2% during phacoemulsification reduced
the incidence of DES and improved patients' satisfaction in both senile and
diabetic cataract patients. It was also effective in maintaining corneal
hydration and was able to significantly reduce the application frequency
intraoperatively.
PMID- 28699062
TI - Rapid Analysis of Ingredients in Cream Using Ultrasonic Mist-Direct Analysis in
Real-Time Time-of-Flight Mass Spectrometry.
AB - A novel method for the simultaneous detection of ingredients in pharmaceutical
applications such as creams and lotions was developed. An ultrasonic atomizer has
been used to produce a mist containing ingredients. The analyte molecules in the
mist can be ionized by using direct analysis in real time (DART) at lower
temperature than traditionally used, and we thus solved the problem of normal
DART-MS measurement using a high-temperature gas. Thereby, molecular-related ions
of heat-unstable components and nonvolatile components became detectable. The
deprotonated molecular ion of glycyrrhizic acid (m/z 821), which is unstable at
high temperatures, was detected without pyrolysis by ultrasonic mist-DART-MS
using unheated helium gas, although it was not detected by normal DART-MS using
heated helium gas. The cationized molecular ions of derivatives of polyethylene
glycol fatty acid monoesters, which are nonvolatile compounds, were also detected
as m/z peaks observed from 800 to 2300. Although the protonated molecular ion of
tocopherol acetate was not detected in ionization by ultrasonic mist, it was
detected by ultrasonic mist-DART-MS even in the emulsion. It was not necessary to
dissolve a sample completely to detect its ions. This method enabled us to obtain
the composition of pharmaceutical applications simply and rapidly. Graphical
Abstract ?.
PMID- 28699063
TI - Determination of Collision Cross Sections Using a Fourier Transform Electrostatic
Linear Ion Trap Mass Spectrometer.
AB - Collision cross sections (CCSs) were determined from the frequency-domain
linewidths in a Fourier transform electrostatic linear ion trap. With use of an
ultrahigh-vacuum precision leak valve and nitrogen gas, transients were recorded
as the background pressure in the mass analyzer chamber was varied between 4* 10
8 and 7 * 10-7 Torr. The energetic hard-sphere ion-neutral collision model,
described by Xu and coworkers, was used to relate the recorded image charge to
the CCS of the molecule. In lieu of our monoisotopically isolating the mass of
interest, the known relative isotopic abundances were programmed into the
Lorentzian fitting algorithm such that the linewidth was extracted from a sum of
Lorentzians. Although this works only if the isotopic distribution is known a
priori, it prevents ion loss, preserves the high signal-to-noise ratio, and
minimizes the experimental error on our homebuilt instrument. Six
tetraalkylammonium cations were used to correlate the CCS measured in the
electrostatic linear ion trap with that measured by drift-tube ion mobility
spectrometry, for which there was an excellent correlation (R 2 ~ 0.9999).
Although the absolute CCSs derived with our method differ from those reported,
the extracted linear correlation can be used to correct the raw CCS. With use of
[angiotensin II]2+ and reserpine, the corrected CCSs (334.9 +/- 2.1 and 250.1 +/-
0.5, respectively) were in good agreement with the reported ion mobility
spectrometry CCSs (335 and 254.3, respectively). With sufficient signal-to-noise
ratio, the CCSs determined are reproducible to within a fraction of a percent,
comparable to the uncertainties reported on dedicated ion mobility instruments.
Graphical Abstract ?.
PMID- 28699064
TI - Joule Heating and Thermal Denaturation of Proteins in Nano-ESI Theta Tips.
AB - Electro-osmotically induced Joule heating in theta tips and its effect on protein
denaturation were investigated. Myoglobin, equine cytochrome c, bovine cytochrome
c, and carbonic anhydrase II solutions were subjected to electro-osmosis in a
theta tip and all of the proteins were denatured during the process. The extent
of protein denaturation was found to increase with the applied square wave
voltage and electrolyte concentration. The solution temperature at the end of a
theta tip was measured directly by Raman spectroscopy and shown to increase with
the square wave voltage, thereby demonstrating the effect of Joule heating
through an independent method. The electro-osmosis of a solution comprised of
myoglobin, bovine cytochrome c, and ubiquitin demonstrated that the magnitude of
Joule heating that causes protein denaturation is positively correlated with
protein melting temperature. This allows for a quick determination of a protein's
relative thermal stability. This work establishes a fast, novel method for
protein conformation manipulation prior to MS analysis and provides a temperature
controllable platform for the study of processes that take place in solution with
direct coupling to mass spectrometry. Graphical Abstract ?.
PMID- 28699065
TI - N-Protonated Isomers and Coulombic Barriers to Dissociation of Doubly Protonated
Ala8Arg.
AB - Collision-induced dissociation (or tandem mass spectrometry, MS/MS) of a
protonated peptide results in a spectrum of fragment ions that is useful for
inferring amino acid sequence. This is now commonplace and a foundation of
proteomics. The underlying chemical and physical processes are believed to be
those familiar from physical organic chemistry and chemical kinetics. However,
first-principles predictions remain intractable because of the conflicting
necessities for high accuracy (to achieve qualitatively correct kinetics) and
computational speed (to compensate for the high cost of reliable calculations on
such large molecules). To make progress, shortcuts are needed. Inspired by the
popular mobile proton model, we have previously proposed a simplified theoretical
model in which the gas-phase fragmentation pattern of protonated peptides
reflects the relative stabilities of N-protonated isomers, thus avoiding the need
for transition-state information. For singly protonated Ala n (n = 3-11), the
resulting predictions were in qualitative agreement with the results from low
energy MS/MS experiments. Here, the comparison is extended to a model tryptic
peptide, doubly protonated Ala8Arg. This is of interest because doubly protonated
tryptic peptides are the most important in proteomics. In comparison with
experimental results, our model seriously overpredicts the degree of backbone
fragmentation at N9. We offer an improved model that corrects this deficiency.
The principal change is to include Coulombic barriers, which hinder the
separation of the product cations from each other. Coulombic barriers may be
equally important in MS/MS of all multiply charged peptide ions. Graphical
Abstract ?.
PMID- 28699066
TI - Effect comparisons among treatment measures on progression-free survival in
patients with skull base chordomas: a retrospective study of 234 post-surgical
cases.
AB - BACKGROUND: Skull base chordoma (SBC) is a rare and refractory tumor with a high
rate of relapse. We aimed to investigate the relationships between different
treatment measures and progression-free survival (PFS) outcomes. METHODS: Data
from 234 SBC patients from one institution were retrieved from a prospectively
maintained database. After grouping, the clinicopathological features and mean
estimated PFS times were subject to inter-group and intra-group comparisons, and
prognostic factors of PFS were estimated by statistical analyses. Two typical
primary patients who suffered from repeated tumor relapses are described.
RESULTS: In addition to pathological subtype (p = 0.005), the initial treatment
measure for the primary cases (n = 180) was identified as an independent factor
of tumor progression (p = 0.002). The patients with gross total resection
exhibited the best mean estimated PFS time (109.5 months). Patients with
intralesional resection exhibited the shortest PFS time (38.3 months), with an
almost significant difference (p = 0.058) compared to those with adjuvant
radiotherapy following intralesional resection (56.6 months). For the recurrent
group (n = 54), marginal resection (p = 0.007) and adjuvant radiotherapy (p =
0.041) were confirmed as independent protective factors for PFS. The longest mean
PFS time (60.3 months) was noted in those patients who received marginal
resection followed by adjuvant radiotherapy. CONCLUSIONS: Treatment measures were
crucial for post-surgical tumor progression in both primary and recurrent cases.
For primary cases, gross total resection and adjuvant radiotherapy offered more
PFS benefits to all patients and those who underwent intralesional resection.
Marginal resection and adjuvant radiotherapy, which are proposed as a general
treatment paradigm for primary tumors, were also equally effective when applied
to relapsing tumors.
PMID- 28699067
TI - Intraoperative clinical testing overestimates the therapeutic window of the
permanent DBS electrode in the subthalamic nucleus.
AB - BACKGROUND: Intraoperative test stimulation is established to optimize target
localization in STN DBS, but requires a time-consuming awake surgery in off
medication state. The aim of this study was to compare the thresholds of
stimulation-induced effects of test stimulation and the permanent electrode.
METHODS: Fifty-nine PD patients receiving bilateral STN DBS were clinically
examined with stepwise increasing monopolar stimulation during surgery and DBS
programming at matched stimulation depths. Thresholds of therapeutic and side
effects were obtained from standardized examination protocols. RESULTS:
Postoperative stimulation via the permanent electrode caused side effects at a
significantly lower threshold than predicted during intraoperative test
stimulation (P < 0.001); whereas sufficient therapeutic effects were achieved at
significantly higher thresholds (P < 0.001). CONCLUSIONS: Intraoperative testing
may lead to an overestimation of the therapeutic window. The two different
electrodes lead to distinct spreading of the electric field in the STN and
surrounding tissues that causes different volume of tissue activated (VTA).
Clinicians involved in DBS surgery and programming should be aware of the
differences in both stimulation settings, concerning electrodes geometry,
stimulation modes as well as the impact of time. Therapeutic and side effects of
permanent stimulation are not predictable by intraoperative test stimulation.
Test stimulation may be an orientating test for very low thresholds of side
effects instead.
PMID- 28699069
TI - Clinical utility of cardiac innervation imaging in patients with heart failure.
PMID- 28699068
TI - Health and Nutritional Status of Vegetarian Candidates for Bariatric Surgery and
Practical Recommendations.
AB - INTRODUCTION: Data on vegetarianism and bariatric surgery (BS) are scarce. We
herein describe the health and nutritional status of vegetarian patients who plan
to undergo BS and propose combined recommendations for vegetarian patients who
undergo BS, based on our clinical experience and current scientific literature in
both nutrition fields. METHODS: Cross-sectional analysis of a prospectively
maintained database of all primary laparoscopic sleeve gastrectomies (LSG)
performed at a bariatric center of excellence between January 2014 and November
2016 was carried out querying patients who declared a vegetarian or vegan
lifestyle before surgery. Preoperative data collected included demographics,
anthropometrics, dietary patterns, supplementation use, physical activity,
smoking habits, co-morbidities, and blood tests. Each vegetarian was matched to
five different omnivores based on age, gender, and BMI. RESULTS: During the study
period, 1470 patients underwent primary LSG surgery (63.7% females). Twenty-one
declared a vegetarian or vegan lifestyle (1.4%) pre-surgery. Most were classified
as lacto-ovo (57.1%) and were driven from ethical reasons (85.7%). No differences
were found between vegetarian and omnivore LSG candidates regarding co
morbidities and nutritional deficiencies, except for lower prevalence of impaired
fasting glucose (14.3 vs. 47.1%;P = 0.007), lower ferritin levels (54.3 +/- 50.5
vs. 96.8 +/- 121.8 ng/ml; P = 0.052) and higher transferrin levels (313.9 +/-
42.7 vs. 278.4 +/- 40.4 mg/dl; P = 0.009) among the vegetarian cohort.
Preoperative use of vitamin B12 and iron supplementation was higher among
vegetarian LSG candidates than their omnivore counterparts (57.1 vs. 6.7%;P <
0.001 and 23.8 vs. 6.7%; P = 0.015, respectively). CONCLUSIONS: Vegetarians have
comparable health status and nutritional deficiencies, lower iron stores, and
higher supplementation use before surgery compared to omnivore LSG candidates.
PMID- 28699070
TI - Noninvasive myocardial blood flow assessment: Another marker of arrhythmic risk?
PMID- 28699071
TI - Microvascular dysfunction in infiltrative cardiomyopathies.
AB - Infiltrative heart diseases are characterized by myocardial tissue alterations
leading to mechanical dysfunction which in turn develops into bi-ventricular
congestive heart failure. Also the coronary microvasculature undergoes
significant remodeling and dysfunction. The effects of the unbalance of the
mechanical cross-talk between cardiac muscle and vessels and of the impairment of
vasodilatory function can be measured non-invasively by means of positron
emission tomography and cardiac magnetic resonance.
PMID- 28699072
TI - Expending Role of Microsatellite Instability in Diagnosis and Treatment of
Colorectal Cancers.
AB - BACKGROUND: Colorectal carcinomas with high-frequency microsatellite instability
(MSI-H) account for 15% of all colorectal cancers, including 12% of sporadic
cases and 3% of cancers associated with Lynch syndrome (also known as hereditary
nonpolyposis colorectal cancer syndrome, HNPCC). Lynch syndrome is an autosomal
dominant hereditary cancer syndrome, caused by germline mutations in mismatch
repair genes, including MLH1, MSH2, MSH6 and PMS2. METHODS: Published articles
from peer-reviewed journals were obtained from PubMed, Google Scholar and
Clinicaltrials.gov . Based on the recent research data, we provide an update on
the MSI testing, along with the evolving role of MSI in diagnosis, prognosis and
treatment of colorectal cancers. RESULTS: Studies have led to significant
advances in the molecular pathogenesis and clinicopathological characteristics of
MSI-H colorectal cancers. Emerging evidence suggests that colorectal cancers with
MSI-H show different outcome and treatment response from those with
microsatellite stable (MSS) tumors. Therefore, MSI testing is essential not only
in the genetic context, but it may also have important prognostic and predictive
value of response to chemotherapy and immunotherapy. CONCLUSIONS: Many experts
and professional authorities have recommended a universal MSI testing in all
individuals newly diagnosed with colorectal cancers.
PMID- 28699074
TI - Front-of-neck airway meets front-of-neck simulation: improving cricothyroidotomy
skills using a novel open-access three-dimensional model and the Airway App.
PMID- 28699073
TI - Sub-therapeutic darunavir concentration and garlic consumption; a "Mediterranean"
drug-food interaction, about 2 cases.
PMID- 28699075
TI - Differential brain activations in adult attention-deficit/ hyperactivity disorder
subtypes: a counting Stroop functional MRI study.
AB - Although previous functional neuroimaging studies have found abnormal brain
activations in individuals with attention deficit hyperactivity disorder (ADHD),
little was known about distinct brain dysfunctions across different ADHD
subtypes. The objective of the present study was to investigate the abnormal
brain activations associated with two ADHD subtypes, predominantly inattentive
(ADHD-PI) and combined (ADHD-C) subtypes. Twenty-five adults with ADHD-PI, 25
with ADHD-C, and 30 healthy controls (HC) participated in this study. The brain
function of the participants were assessed by using the counting Stroop task
inside the scanner and the Conners' Continuous Performance Test (CCPT) outside
the scanner. The HC group showed greater activations in the caudate nucleus and
inferior frontal gyrus (IFG) than the ADHD-PI and ADHD-C groups. The ADHD-PI
group showed greater activations in the superior parietal lobule (SPL) than the
ADHD-C group. In all participants with ADHD, we found negative correlations of
activation in the left caudate and the left IFG with the standard deviation of
the reaction time of the CCPT, and negative correlations of activation in the
left SPL with the reaction time changes across different inter-stimulus
intervals. Our results demonstrated altered brain activity in the frontostriatal
networks of adults with ADHD-PI and the fronto-striato-parietal networks of
adults with ADHD-C. Abnormalities in the parietal areas may represent the main
difference between the ADHD-PI and ADHD-C subtypes.
PMID- 28699076
TI - Exploring the effects of acid mine drainage on diatom teratology using geometric
morphometry.
AB - Metal pollution of aquatic habitats is a major and persistent environmental
problem. Acid mine drainage (AMD) affects lotic systems in numerous and
interactive ways. In the present work, a mining area (Rosia Montana) was chosen
as study site, and we focused on two aims: (i) to find the set of environmental
predictors leading to the appearance of the abnormal diatom individuals in the
study area and (ii) to assess the relationship between the degree of valve
outline deformation and AMD-derived pollution. In this context, morphological
differences between populations of Achnanthidium minutissimum and A.
macrocephalum, including normal and abnormal individuals, were evidenced by means
of valve shape analysis. Geometric morphometry managed to capture and
discriminate normal and abnormal individuals. Multivariate analyses (NMDS, PLS)
separated the four populations of the two species mentioned and revealed the main
physico-chemical parameters that influenced valve deformation in this context,
namely conductivity, Zn, and Cu. ANOSIM test evidenced the presence of
statistically significant differences between normal and abnormal individuals
within both chosen Achnanthidium taxa. In order to determine the relative
contribution of each of the measured physico-chemical parameters in the observed
valve outline deformations, a PLS was conducted, confirming the results of the
NMDS. The presence of deformed individuals in the study area can be attributed to
the fact that the diatom communities were strongly affected by AMD released from
old mining works and waste rock deposits.
PMID- 28699077
TI - Focusing attention on ancestral diversity within genomics research: a potential
means for promoting equity in the provision of genomics based healthcare services
in developing countries.
AB - Although we are well into the second decade after the completion of the
International Human Genome Project, genomic research has failed to fully
represent the diverse ancestry of global populations. The resultant healthcare
challenges faced by populations underrepresented in genomic research needs to be
tackled by the global scientific community. In this paper, we address several
major factors which have contributed to the existing health disparity and put
forward a combination of scientific and political interventions needed to bring
about a change that will ensure all global populations benefit equally from the
advances made in genomic medicine and research.
PMID- 28699078
TI - Characterization of AKR4C15, a Novel Member of Aldo-Keto Reductase, in Comparison
with Other Rice AKR(s).
AB - Environmental stresses often cause a rapid and excessive accumulation of reactive
oxygen species (ROS), the toxicity of which is further amplified by downstream
aldehyde production. Aldo-keto reductase (AKR) is a group of enzymes metabolizing
aldehyde/ketone to the corresponding alcohol using NADPH as the cofactor. In this
study, OsI_20197 (AKR4C15), a novel member of AKR4 subfamily C, was isolated and
biochemically characterized. Kinetic studies on bacterially-expressed recombinant
AKR4C15 revealed that the enzyme was capable of metabolizing a wide variety of
aldehydes but clearly exhibited a preference for three carbon compounds, i.e.
methylglyoxal, malondialdehyde and glyceraldehyde. In comparison with His-tagged
proteins of AKR4C9 from Arabidopsis and several other rice AKR(s): OsI_04426,
OsI_04428, OsI_04429, and OsI_15387, AKR4C15 was the one capable of most
efficiently metabolizing MDA and had the highest value of catalytic efficiency,
which was higher than the value of AKR4C9, approximately, by 30-fold; while its
capability of metabolizing MG was on par with AKR4C9, OsI_04426 and OsI_04428
(AKR4C14); and was considerably higher than the activity of OsI_04429 and
OsI_15387. In vivo research on transgenic Arabidopsis seedlings ectopically
expressing AKR4C15 showed that the levels of both MDA and MG were also
significantly lower than the levels in wild-type seedlings under both normal and
stress conditions, emphasizing the role of AKR4C15 in MG and MDA metabolism. In
conclusion, AKR4C15, together with OsI_04426 and AKR4C14, may play protective
roles against small reactive aldehydes and medium-chain aldehydes.
PMID- 28699079
TI - Carcinoma of gallbladder: Clinical evaluation and survival rate at a tertiary
care center in Rajasthan.
PMID- 28699080
TI - [Corneal nerve plexus visible using confocal microscopy as biomarker].
PMID- 28699082
TI - Combat Stress Decreases Memory of Warfighters in Action.
AB - The present research aimed to analyze the effect of combat stress in the
psychophysiological response and attention and memory of warfighters in a
simulated combat situation. Variables of blood oxygen saturation, heart rate,
blood glucose, blood lactate, body temperature, lower body muscular strength
manifestation, cortical arousal, autonomic modulation, state anxiety and memory
and attention through a postmission questionnaire were analyzed before and after
a combat simulation in 20 male professional Spanish Army warfighters. The combat
simulation produces a significant increase (p < 0.05) in explosive leg strength,
rated perceived exertion, blood glucose, blood lactate, somatic anxiety, heart
rate, and low frequency domain of the HRV (LF) and a significant decrease of high
frequency domain of the heart rate variability (HF). The percentage of correct
response in the postmission questionnaire parameters show that elements more
related with a physical integrity threat are the most correctly remembered. There
were significant differences in the postmission questionnaire variables when
participants were divided by the cortical arousal post: sounds no response,
mobile phone correct, mobile phone no response, odours correct. The correlation
analysis showed positive correlations: LF post/body temperature post, HF
post/correct sound, body temperature post/glucose post, CFFTpre/lactate post,
CFFT post/wrong sound, glucose post/AC pre, AC post/wrong fusil, AS post/SC post
and SC post/wrong olfactory; and negative correlations: LF post/correct sound,
body temperature post/lactate post and glucose post/lactate post. This data
suggest that combat stress actives fight-flight system of soldiers. As
conclusion, Combat stress produces an increased psychophysiological response that
cause a selective decrease of memory, depending on the nature, dangerous or
harmless of the objects.
PMID- 28699083
TI - A Therapy System for Post-Traumatic Stress Disorder Using a Virtual Agent and
Virtual Storytelling to Reconstruct Traumatic Memories.
AB - Although post-traumatic stress disorder (PTSD) is well treatable, many people do
not get the desired treatment due to barriers to care (such as stigma and cost).
This paper presents a system that bridges this gap by enabling patients to follow
therapy at home. A therapist is only involved remotely, to monitor progress and
serve as a safety net. With this system, patients can recollect their memories in
a digital diary and recreate them in a 3D WorldBuilder. Throughout the therapy, a
virtual agent is present to inform and guide patients through the sessions,
employing an ontology-based question module for recollecting traumatic memories
to further elicit a detailed memory recollection. In a usability study with
former PTSD patients (n = 4), these questions were found useful for memory
recollection. Moreover, the usability of the whole system was rated positively.
This system has the potential to be a valuable addition to the spectrum of PTSD
treatments, offering a novel type of home therapy assisted by a virtual agent.
PMID- 28699084
TI - EGFR Mutation Testing of non-squamous NSCLC: Impact and Uptake during
Implementation of Testing Guidelines in a Population-Based Registry Cohort from
Northern New Zealand.
AB - BACKGROUND: Since 2013, clinical practice guidelines recommend EGFR mutation
testing of non-squamous NSCLC to select advanced-stage patients for first-line
treatment using EGFR-TKIs. OBJECTIVE: We aimed to determine population-based
trends in the real-world uptake and impact in routine practice of these recently
updated testing guidelines. PATIENTS AND METHODS: A population-based
observational study was conducted of notifications to the New Zealand Cancer
Registry of patients eligible for EGFR testing diagnosed in northern New Zealand
between January 2010 and April 2014. The main study variable was EGFR mutation
testing. Main outcome measures (overall survival and dispensing of EGFR-TKIs)
were extracted from prospectively archived electronic databases until October
2015. RESULTS: The population-based cohort of 1857 patients had an average age of
70 years. Most had adenocarcinoma and metastatic disease at diagnosis. EGFR
testing was undertaken in 500 patients (27%) with mutations detected in 109
patients (22%). EGFR testing increased during the period of study from <5% to 67%
of patients (P < 0.0001). Full uptake of testing by all eligible patients was
limited by a lack of availability of specimens for testing and variable testing
referral practices. The proportion of patients treated with EGFR-TKIs decreased
during the same time period, both among untested patients (from 12.2% to 2.8% (P
< 0.0001)) and in the population as a whole (from 13.7% to 10.6% (P < 0.05)).
EGFR testing was associated with prolonged overall survival (Adjusted HR = 0.76
(95% CI, 0.65-0.89) Log-rank P < 0.0001) due at least in part to the much longer
overall survival achieved by mutation-positive patients, of whom 79% received
EGFR-TKIs. Compared to untested EGFR-TKI-treated patients, mutation-positive EGFR
TKI-treated patients received EGFR-TKIs for longer, and survived longer both from
the start of EGFR-TKI treatment and date of their diagnosis. CONCLUSIONS: In this
real world setting, high uptake of EGFR testing was achieved and associated with
major changes in EGFR-TKI prescribing and improved health outcomes. Modifiable
factors determined testing uptake. Study registration ACTRN12615000998549.
PMID- 28699085
TI - Laser Interstitial Thermal Therapy for Epilepsy.
AB - MRI-guided laser interstitial thermal therapy (MgLiTT) uses a narrow diameter
cannula to stereotactically target and heat deeper cerebral structures. This
technique produces a precise lesion in the brain with great reliability because
the localized tissue temperature change is monitored in real time. Because MgLiTT
minimizes injury to surrounding brain, it appears to have a lower risk of
affecting normal neurological function, and because it is done through a burr
hole, there is less operative risk, less discomfort, and shorter
hospitalizations. It is FDA approved for soft tissue ablation and is being
increasingly applied to the surgical treatment of epilepsy, especially when
seizures arise from deeper structures such as the hippocampus, amygdala, or
discrete dysplastic tissue such as hypothalamic hamartomas. Mesial temporal
epilepsy is the most frequently encountered surgically remedial epilepsy suitable
for MgLiTT, particularly when there is unilateral hippocampal sclerosis. There is
emerging evidence that it can be effective for eliminating seizures in this type
of epilepsy, and that it has a lower risk of cognitive deficits than anterior
temporal lobectomy.
PMID- 28699086
TI - Estimating Direct Cost of Cystic Fibrosis Care Using Irish Registry Healthcare
Resource Utilisation Data, 2008-2012.
AB - BACKGROUND: Understanding the determinants of cost of cystic fibrosis (CF) care
and health outcomes may be useful for financial planning for the delivery of CF
services. Registries contain information otherwise unavailable to healthcare
activity/cost monitoring systems. We estimated the direct medical cost of CF care
using registry data and examined how cost was affected by patient characteristics
and CF gene (CF Transmembrane Conductance Regulator [CFTR]) mutation. METHODS:
Healthcare resource utilisation data (2008-2012) were obtained for CF patients
enrolled with the Irish CF Registry by 2013 from linked registry and national
hospitalisation database records. Mean annual hospitalisation and medication per
patient costs were estimated by demographic profile, CFTR mutation, clinical
status, and CF co-morbidity, and were presented in 2014 euro values. A mixed
effects regression model was used to examine the effect of demographic, CFTR
mutation, and clinical outcomes on the log10 cost of direct medical CF care.
RESULTS: Using 4261 observations from 1100 patients, we found that the median
annual total cost per patient increased over the period 2008-2012 from ?12,659 to
?16,852, inpatient bed-day cost increased from ?14,026 to ?17,332, and medication
cost increased from ?5863 to ?12,467. Homozygous F508-CFTR mutation (class II)
cost was highest and milder mutation (class IV/V) cost was 49% lower. Baseline
estimated cost in 2008 for a hypothetical underweight, homozygous F508del-CFTR 6
year-old female without chronic Pseudomonas aeruginosa/Staphylococcus aureus, CF
related diabetes (CFRD) or methicillin-resistant S. aureus (MRSA), and with a
poor percent predicted forced expiratory volume in 1 s (ppFEV1) was ?10,113, and
was ?21,082 in a 25-year-old with the same hypothetical profile. Chronic P.
aeruginosa infection increased baseline cost by 39%, CF co-morbidity diabetes by
18%, and frequency of pulmonary exacerbation by 15%. Underweight, declining
ppFEV1, chronic S. aureus colonisation, and time also influenced cost.
CONCLUSIONS: CFTR mutation is an important factor influencing the cost of CF
care. Costs differ among cohorts of CF patients eligible to access new and
emerging CFTR repair therapies. These findings support the evaluation of outcome
associated cost in CFTR mutation-specific CF patient groups.
PMID- 28699087
TI - Effects of endurance training on autophagy and apoptotic signaling in visceral
adipose tissue of prolonged high fat diet-fed rats.
AB - PURPOSE: Autophagy and apoptosis play critical roles in both development and
tissue homeostasis in response to (patho)physiological stimuli, such as high-fat
diet (HFD) and endurance training (ET). Therefore, we aimed to investigate how ET
modulates autophagy and apoptotic-related signaling in visceral adipose tissue of
long-standing HFD-fed rats. METHODS: The study was conducted over a 17-week
period on Sprague-Dawley rats, which were divided into four groups (n = 8/group):
standard diet sedentary (STD+SED), high-fat diet sedentary (HFD+SED), standard
diet ET (STD+ET) and high-fat diet ET (HFD+ET). After 9 weeks of dietary
regimens, ET groups were trained for 8 weeks on treadmill (5 days/week at 25
m/min for 60 min/day), while maintaining dietary regimens. Autophagy and
apoptotic-signaling markers in epididymal white adipose tissue (eWAT) were
determined using RT-qPCR, Western blot and spectrometry techniques. RESULTS: ET
reduced body weight, visceral fat mass and HOMA-IR in standard and HF diet-fed
animals. Moreover, ET reverted the HFD-induced increases in the percentage of
larger adipocytes and also reduced the percentage of smaller adipocytes. The HFD
decreased pre-adipocyte factor 1 (DLK1/PREF1) and increased the pro-apoptotic
markers (Bax protein and caspase 3-like activity), while having no impact on
autophagy markers. However, ET increased DLK1/PREF1 and Bcl-2 in both diet types,
while decreasing Bax and caspases 9, 8 and 3-like activities in HFD feeding rats.
Additionally, Beclin-1 and p62 protein significantly increased in ET groups of
both diet types. CONCLUSIONS: Data demonstrate that 8 weeks of ET was effective
in attenuating apoptotic-related signaling in long-standing HFD-fed rats.
Moreover, HFD and ET had no impact on VAT autophagy markers.
PMID- 28699088
TI - Sepsis prediction in critically ill patients by platelet activation markers on
ICU admission: a prospective pilot study.
AB - BACKGROUND: Platelets have been involved in both immune surveillance and host
defense against severe infection. To date, whether platelet phenotype or other
hemostasis components could be associated with predisposition to sepsis in
critical illness remains unknown. The aim of this work was to identify platelet
markers that could predict sepsis occurrence in critically ill injured patients.
METHODS: This single-center, prospective, observational, 7-month study was based
on a cohort of 99 non-infected adult patients admitted to ICUs for elective
cardiac surgery, trauma, acute brain injury, and post-operative prolonged
ventilation and followed up during ICU stay. Clinical characteristics and
severity score (SOFA) were recorded on admission. Platelet activation markers,
including fibrinogen binding to platelets, platelet membrane P-selectin
expression, plasma soluble CD40L, and platelet-leukocytes aggregates were assayed
by flow cytometry at admission and 48 h later, and then at the time of sepsis
diagnosis (Sepsis-3 criteria) and 7 days later for sepsis patients.
Hospitalization data and outcomes were also recorded. METHODS: Of the 99
patients, 19 developed sepsis after a median time of 5 days. These patients had a
higher SOFA score at admission; levels of fibrinogen binding to platelets
(platelet-Fg) and of D-dimers were also significantly increased compared to the
other patients. Levels 48 h after ICU admission no longer differed between the
two patient groups. Platelet-Fg % was an independent predictor of sepsis (P =
0.0031). By ROC curve analysis, cutoff point for Platelet-Fg (AUC = 0.75) was
50%. In patients with a SOFA cutoff of 8, the risk of sepsis reached 87% when
Platelet-Fg levels were above 50%. Patients with sepsis had longer ICU and
hospital stays and higher death rate. CONCLUSIONS: Platelet-bound fibrinogen
levels assayed by flow cytometry within 24 h of ICU admission help identifying
critically ill patients at risk of developing sepsis.
PMID- 28699089
TI - Cardiovascular Safety of Antidiabetic Drugs in the Hospital Setting.
AB - PURPOSE OF REVIEW: Patients with diabetes and/or stress hyperglycemia requires
good glycemic control in the hospital setting, often requiring the use of glucose
lowering therapy. Standard-of-care dictates that non-insulin therapy be
discontinued, with insulin therapy initiated using a basal-bolus approach.
However, insulin is associated with a high risk for hypoglycemia and medical
errors. Alternatives to insulin are needed in the inpatient setting, but the
cardiovascular (CV) safety of non-insulin therapy is a concern. RECENT FINDINGS:
Most studies of antidiabetic drugs have been performed in the outpatient setting,
and except for insulin therapy, trials in the inpatient setting have been
insufficient to establish CV safety. Randomized controlled trials support the
safety of insulin with more moderate glycemic control in the hospital, when
hypoglycemia is minimized. Two recent multicenter randomized controlled clinical
trials support the safety of sitagliptin, a dipeptidylpeptidase-4 inhibitor
(DPP4i), in hospitalized patients, although the sample sizes were likely too
small to detect CV events. Small trials suggest a possible CV benefit of glucagon
like peptide-1 receptor agonist therapy. A paucity of evidence and presence of
side effects and cautions with insulin secretagogues, sodium glucose-co
transporter-2 inhibitors, and metformin preclude their routine use in the
hospital setting. Available evidence is inadequate to evaluate the CV safety of
most antidiabetic drug classes in the hospital setting. However, preliminary data
from randomized clinical trials suggest the potential safety of the DPP4i
sitagliptin.
PMID- 28699090
TI - Physical Behavior Profiles in Chronic Cancer-Related Fatigue.
AB - PURPOSE: Increasing physical activity level is a generally effective intervention
goal for patients who suffer from chronic cancer-related fatigue (CCRF). However,
patients are unlikely to benefit equally from these interventions, as their
behavioral starting points might vary substantially. Therefore, we explored
patterns of physical behavior of participants who suffer from CCRF. METHODS:
Baseline data of a randomized controlled trial were used for a latent profile
analysis on nine accelerometer-derived physical behavior measures, describing
levels and patterns of physical activity, moderate-to-vigorous intensity physical
activity (MVPA), and sedentary behavior. The relation between participant
characteristics and the latent profiles was analyzed. RESULTS: Accelerometer data
of 172 participants from the Netherlands was analyzed. Three latent profiles were
distinguished that differed most on physical activity level and total time spent
in MVPA. Eighty-eight percent of all participants were assigned to a profile with
a probability higher than 8. Age and perceiving limitations by comorbid
conditions and pain were significant covariates of profile membership.
CONCLUSIONS: We distinguished three physical behavior profiles. The differences
between the patterns indicate that the heterogeneity of this sample requires
patients to have substantially different treatment goals. Further research should
test the applicability of these profiles in clinical practice.
PMID- 28699091
TI - The effects of ozone application on genotoxic damage and wound healing in
bisphosphonate-applied human gingival fibroblast cells.
AB - OBJECTIVES: Medication-related osteonecrosis of the jaws (MRONJ) is an extremely
therapy-resistant disease involving the jaws especially following bisphosphonate
treatment. Bisphosphonates accumulate in bone in concentrations sufficient to be
directly toxic to the oral epithelium. Current therapeutic options are inadequate
for the prevention and treatment of MRONJ. The aim of this study was to
investigate effects of ozone gas plasma therapy on wound healing in
bisphosphonate-applied human fibroblasts. MATERIAL AND METHODS: Human primary
gingival fibroblasts were cultured. Cytotoxic concentrations (IC50) of
bisphosphonates (pamidronate (PAM), alendronate (ALN), and zoledronate (ZOL))
were determined by MTT test. A 60 MUg/MUl for 30 s of ozone gas plasma
application was performed to all experimental culture flasks after drug treatment
at 24-h intervals as 3 s/cm2. Genotoxic damages were evaluated by comet assay and
wound healing was determined by in vitro scratch assay. RESULTS: PAM, ALN, and
ZOL applications caused genotoxic damage on primary human gingival fibroblast
DNA. Ozone gas plasma therapy significantly decreased the genotoxic damage (p <
0.05), and this application provided 25, 29, and 27% less genotoxic damage in
order of ALN, PAM, and ZOL groups. Ozone gas plasma therapy significantly
increased wound healing rates both in postsurgical 24th and 48th hours for all
doses of experimental drug groups (p < 0.05). CONCLUSION: The ozone gas plasma
application decreased genotoxic damage effect of bisphosphonate usage while
improved the wound closure rate on human gingival fibroblasts. CLINICAL
RELEVANCE: Ozone gas plasma therapy may be helpful in prevention of gingival
healing delay in MRONJ pathogenesis especially when applied simultaneously with
surgical intervention.
PMID- 28699092
TI - Impact of venous invasion on the efficacy of adjuvant chemotherapy in elderly
patients with stage III colorectal cancer.
AB - One of the reasons for the underuse of adjuvant chemotherapy in elderly patients
with stage III colorectal cancer is a small survival benefit. This retrospective
study sought to identify the predictive factors for elderly patients who could
obtain a sufficient survival benefit. We reviewed the data of 1354 elderly
patients (aged >=70 years) with stage III colorectal cancer who underwent
complete resection between January 1997 and December 2006. The efficacy of
adjuvant chemotherapy was assessed, and the risk factors for recurrence were
determined. The efficacy of adjuvant chemotherapy was also assessed after
stratification for the above-mentioned risk factors for recurrence. There was a
tendency for adjuvant chemotherapy to be effective in elderly patients (hazard
ratio 0.84; 95% CI 0.70-1.01). Age, tumor location, pathology findings, tumor
depth, venous invasion and lymph node metastasis were identified to be
independent risk factors for recurrence by univariate and multivariate analyses.
Among these factors, adjuvant chemotherapy was much effective in the elderly
patients with high venous invasion (v2-3) (hazard ratio 0.69; 95% CI 0.52-0.91).
High venous invasion (v2-3) was identified to be a predictive factor for elderly
patients with stage III colorectal cancer who gained a sufficient survival
benefit.
PMID- 28699093
TI - Evaluating Facility-Based Decision-Making in Women with a Prior Cesarean Delivery
and Association with Maternal and Perinatal Outcomes.
AB - Objective To describe facility-based decision-making for women with one prior
cesarean delivery (CD) in a resource-limited setting and to characterize maternal
and perinatal outcomes in these groups. Methods One year retrospective study of
women with one prior CD delivering at Korle-Bu Teaching Hospital (KBTH), Ghana.
Women were categorized into three groups based on initial plan of management on
admission [trial of labor after cesarean (TOLAC), emergency repeat CD (EMCD) or
non-emergent repeat CD (RCD)]. Characteristics and outcomes across these groups
were then compared. Results During the study period, 1247 women with one prior CD
delivered at KBTH, of which 377 (30.2%) were triaged to RCD, 439 (35.2%) to EMCD
and 431 (34.6%) to TOLAC. Twelve uterine ruptures and no maternal deaths
occurred. Perinatal mortality was 4.2% (n = 52). Compared to the RCD group, the
TOLAC group had a lower risk for maternal adverse events (aOR 0.3, 95% CI 0.1
1.0; p = 0.04) and non-significant higher risk of perinatal adverse events (aOR
1.6, 95% CI 0.7-3.3; p = 0.25). Compared to women triaged to RCD, the EMCD group
had a non-significant increase in risk of maternal adverse events (aOR 1.6, 95%
CI 0.8-3.5; p = 0.2) and a significantly higher rate of perinatal adverse events
(aOR 2.4, 95% CI 1.2-4.9; p = 0.01). Conclusions for Practice Women triaged to
EMCD at admission are different when compared to women allowed a TOLAC or offered
a non-emergent RCD. These women bear increased rates of adverse outcomes and
should be considered as a separate group for analysis in future studies conducted
in similar settings.
PMID- 28699094
TI - Emergency Contraception in Mexico: Trends in Knowledge and Ever-Use 2006-2014.
AB - Objectives A package of interventions to introduce emergency contraception (EC)
to Mexico was implemented, resulting in the addition of EC to the national family
planning guidelines in 2004. We describe EC knowledge and use among women in
Mexico over time. Methods We used the 2006, 2009, and 2014 of waves of a
nationally representative demographic survey (ENADID). We assessed EC knowledge
and usage in women ages 15-29 who are not using permanent methods and tested
whether EC knowledge and use is changing over time after controlling for socio
demographic characteristics using logistic regression. Results Our sample
included n = 99,223 (population N = 40,234,355) women ages 15-29. Overall,
knowledge of EC increased over time: 62% in 2006 to 79% in 2009 to 83% in 2014 (p
< 0.001). Among young women who have used contraception (n = 42,883; N =
16,816,701), the proportion that reported EC use increased from 3 to 11% to 29%
(p < 0.001). Compared to non-users, women who had ever used EC were more likely
to be using no method of contraception (44 vs. 35%) or barrier method (22 vs.
17%). Demographic factors including lower wealth, lower education, indigenous
status and rural living are significantly associated with less EC knowledge and
use. Stratified multivariate analysis found that demographic disadvantages
magnify lower EC use among rural residents compared to non-rural residents.
Conclusions for Practice Knowledge and use of EC are growing rapidly in Mexico,
but disparities persist in demographically disadvantaged women, particularly
those living in rural areas. Women who use EC appear to be at higher risk of
unintended pregnancy based on current contraceptive use.
PMID- 28699095
TI - Maternal Education Gradients in Infant Health in Four South American Countries.
AB - Objective We investigate gradients (i.e. differences) in infant health outcomes
by maternal education in Argentina, Brazil, Chile, and Venezuela and explore
channels related to father's education, household labor outcomes, and maternal
health, fertility, and use of prenatal services and technology. Methods We employ
secondary interview and birth record data similarly collected across a network of
birth hospitals from the early 1980s through 2011 within the Latin American
Collaborative Study of Congenital Anomalies (ECLAMC). Focusing on children
without birth defects, we estimate gradients in several infant health outcomes
including birth weight, gestational age, and hospital discharge status by
maternal education using ordinary least squares regression models adjusting for
several demographic factors. To explore channels, we add as covariates father's
education, parental occupational activity, maternal health and fertility history,
and use of prenatal services and technology and evaluate changes in the
coefficient of maternal education. We use the same models for each country
sample. Results We find important differences in gradients across countries. We
find evidence for educational gradients in preterm birth in three countries but
weaker evidence for gradients in fetal growth. The extent to which observed
household and maternal factors explain these gradients based on changes in the
regression coefficient of maternal education when controlling for these factors
as covariates also varies between countries. In contrast, we generally find
evidence across all countries that higher maternal education is associated with
increased use of prenatal care services and technology. Conclusions Our findings
suggest that differences in infant health by maternal education and their
underlying mechanisms vary and are not necessarily generalizable across
countries. However, the positive association between maternal education and use
of prenatal services and technology is more consistent across examined countries.
PMID- 28699096
TI - Hepatitis C Cascade of Care Among Pregnant Women on Opioid Agonist
Pharmacotherapy Attending a Comprehensive Prenatal Program.
AB - Background Given the large increases in opioid use among pregnant women and
associations with hepatitis C virus (HCV) infection, screening pregnant women who
are on (opioid agonist) pharmacotherapy for HCV infection has potential to inform
medical care for these mothers as well as their newborns. We investigated the HCV
testing cascade among pregnant women on pharmacotherapy in order to describe
exposure and infection rates and to identify opportunities that would improve
care. Methods Secondary analyses of laboratory results were performed for HCV
testing, including anti-HCV, viremia (RNA) and genotype. Information was
abstracted from the medical records of women who were followed at a comprehensive
prenatal care clinic for women with substance use disorders at the University of
New Mexico. Results The sample included 190 pregnant women, of whom 188 were on
pharmacotherapy (43.7% on buprenorphine and 55.3% on methadone); the remaining
two had tested positive for heroin or prescription opioids. A total of 178
(93.7%) were tested for anti-HCV, 94 (98.9%) of whom were tested for RNA, and 41
(57.7%) were genotyped. Prevalence of exposure to HCV by anti-HCV results was
53.3%, and 37.3% were positive for HCV RNA indicating chronic infection.
Conclusions The high prevalence of exposure and infection with HCV in pregnant
women involved in pharmacotherapy for a substance use disorder indicate a need
for ongoing surveillance and testing for HCV. Identifying HCV during pregnancy is
crucial because this identification would serve to enhance medical care and
potentially prevent vertical transmission. Identifying HCV would also facilitate
referrals to newly available curative HCV treatments following delivery.
PMID- 28699097
TI - Early Preterm Birth Across Generations Among Whites and African-Americans: A
Population-Based Study.
AB - Objectives To determine the extent to which non-Latina White and African-American
mother's gestational age is associated with extremely early (<30 weeks), modestly
early (30-33 weeks), and late (34-36 weeks) infant preterm birth (PTB) rates.
Methods Race-specific stratified and multivariable logistic regression analyses
were performed on the Illinois Transgenerational Birth File of non-Latino White
and African-American infants (born 1989-1991) and their mothers (born 1956-1976).
Results White mothers (n = 184) born at <30 weeks had a greater extremely early
infant PTB rate than White mothers (n = 131,980) born at term: 1.6 versus 0.5%,
respectively; RR = 3.6 (1.2, 11.0). African-American mothers (n = 269) born at
<30 weeks had a greater extremely early infant PTB rate than African-American
mothers (n = 34,885) born at term: 4.1 versus 2.1%, respectively; RR = 2.0 (1.1,
3.6). In logistic regression models the adjusted (controlling for maternal age,
education, parity, prenatal care, marital status, and cigarette smoking) OR of
extremely early PTB for White and African-American mothers born <30 (compared to
>=37) weeks equaled 4.0 (1.2, 12.6) and 2.3 (1.2, 4.3), respectively. The
adjusted OR of modestly early PTB for White and African-American mothers born 30
33 (compared to >=37) weeks equaled 1.6 (1.0, 2.5) and 1.3 (0.9, 1.7),
respectively. The adjusted OR of late PTB for White and African-American mothers
born 34-36 (compared to >=37) weeks equaled 1.2 (1.0, 1.3) and 1.1 (1.0, 1.2),
respectively. Conclusions A generational association of extremely early, but not
modestly early or late, PTB exists among non-Latino Whites and African-Americans.
PMID- 28699098
TI - Effects of a 2014 Statewide Policy Change on Cash-Value Voucher Redemptions for
Fruits/Vegetables Among Participants in the Supplemental Nutrition Program for
Women, Infants, and Children (WIC).
AB - Purpose In 2014, the New Jersey Special Supplemental Nutrition Program for Women,
Infants, and Children (WIC) began requiring WIC-authorized stores to stock at
least two fresh fruits and two fresh vegetables. We aimed to evaluate the effect
of this policy change on fruit and vegetable purchases among WIC-participating
households and to assess variation by household access to a healthy food store
such as a supermarket or large grocery store. Description Households with
continuous WIC enrollment from June 2013 to May 2015 were included (n = 16,415).
Participants receive monthly cash-value vouchers (CVVs) to purchase fruits and
vegetables. For each household, the CVV redemption proportion was calculated for
the period before and after the policy by dividing the total dollar amount
redeemed by the total dollar amount issued. Complete redemption was defined as a
proportion >=90% and the change in complete redemption odds was assessed after
adjusting for Supplemental Nutrition Assistance Program participation. Assessment
We observed a small increase following the policy change [odds ratio (OR) 1.10,
95% confidence interval (CI) 1.04-1.17]; however, the effect varied by healthy
food access (p = 0.03). The odds increased for households with access to at least
one healthy food store (OR 1.13, 95% CI 1.06-1.20) while no effect was observed
for households without such access (OR 0.91, 95% CI 0.76-1.10). Conclusion Policy
change was associated with a small increase in purchasing, but only among
households with healthy food access. The state is addressing this gap through
technical assistance interventions targeting WIC-authorized small stores in
communities with limited access.
PMID- 28699099
TI - Fertility Intentions and Residential Relocations.
AB - This research addresses the question of whether fertility intentions (before
conception) are associated with residential relocations and the distance of the
relocation. We empirically tested this using data from two birth cohorts (aged 24
28 and 34-38 in the first survey wave) of the German Family Panel (pairfam) and
event history analysis. Bivariate analyses showed that coupled individuals
relocated at a higher rate if they intended to have a(nother) child. We found
substantial heterogeneity according to individuals' age and parental status,
particularly for outside-town relocations. Childless individuals of average age
at family formation-a highly mobile group-relocated at a lower rate if they
intended to have a child. In contrast, older individuals who already had children
the least-mobile group-relocated at a higher rate if they intended to have
another child. Multivariate analyses show that these associations are largely due
to adjustments in housing and other living conditions. Our results suggest that
anticipatory relocations (before conception) to adapt to growing household size
are importantly nuanced by the opportunities and rationales of couples to adjust
their living conditions over the life course. Our research contributes to the
understanding of residential mobility as a by-product of fertility decisions and,
more broadly, evidences that intentions matter and need to be considered in the
analysis of family life courses.
PMID- 28699100
TI - Reward devaluation disrupts latent inhibition in fear conditioning.
AB - Three experiments explored the link between reward shifts and latent inhibition
(LI). Using consummatory procedures, rewards were either downshifted from 32% to
4% sucrose (Experiments 1-2), or upshifted from 4% to 32% sucrose (Experiment 3).
In both cases, appropriate unshifted controls were also included. LI was
implemented in terms of fear conditioning involving a single tone-shock pairing
after extensive tone-only preexposure. Nonpreexposed controls were also included.
Experiment 1 demonstrated a typical LI effect (i.e., disruption of fear
conditioning after preexposure to the tone) in animals previously exposed only to
4% sucrose. However, the LI effect was eliminated by preexposure to a 32%-to-4%
sucrose devaluation. Experiment 2 replicated this effect when the LI protocol was
administered immediately after the reward devaluation event. However, LI was
restored when preexposure was administered after a 60-min retention interval.
Finally, Experiment 3 showed that a reward upshift did not affect LI. These
results point to a significant role of negative emotion related to reward
devaluation in the enhancement of stimulus processing despite extensive
nonreinforced preexposure experience.
PMID- 28699101
TI - Systematic Review and Meta-analysis of Parent Group Interventions for Primary
School Children Aged 4-12 Years with Externalizing and/or Internalizing Problems.
AB - This systematic review and meta-analysis evaluates the efficacy of parent
training group interventions to treat child externalizing and/or internalizing
problems. A search identified 21 randomized controlled trials of parent group
interventions aimed at ameliorating child externalizing and/or internalizing
problems in children aged 4-12 years. Random effects meta-analyses yielded
significant pooled treatment effect size (g) estimates for child externalizing (g
= -0.38) and internalizing problems (g = -0.18). Child anxiety symptoms or
internalizing problems evident in children with externalizing behavior problems
did not change significantly following intervention. Study quality was a
statistically significant moderator of treatment response for child externalizing
problems, however hours of planned parent group treatment and treatment recipient
were not. Findings support the use of parent group interventions as an effective
treatment for reducing externalizing problems in children aged 4-12 years. Whilst
statistically significant, programs had a limited impact on internalizing
symptoms, indicating a need for further investigation.
PMID- 28699102
TI - [The concept of schizoidia in psychiatry : From schizoidia to schizotypy and
cluster A personality disorders].
AB - From a perspective of conceptual evolution schizoidia was initially considered to
describe features both of the premorbid personality of schizophrenic patients and
of the personalities of non-psychotic family members (Bleuler, Kahlbaum,
Kraepelin). On a psychopatholocial level a close link to the complex basic
symptom of autism was stressed. From the very beginnings of modern psychiatry
schizoidia was discussed within a conceptual frame of schizophrenia spectrum
disorders (Kretschmer, Hoch, Polatin). Approaches to operationalize these
conceptual works laid the basis for the cluster A personalities in DSM-III. Due
to the prominent concept of schizotypy (Kety, Rado, Meehl) three split up
diagnostic categories of schizotypal, schizoid and paranoid personality disorders
resulted. Cluster A personality disorders are frequent in community-based
epidemiological studies. Health-care seeking behaviour due to primary personality
related problems, however, seems to be less paramount compared to cluster B and C
personality disorders. Many family- and twin-based genetic studies convincingly
stress a close link between schizotypal personality disorder and schizophrenia.
This link is less pronounced for paranoid personality disorder, and even
vanishingly low for schizoid personality disorder. From a perspective of
schizophrenia spectrum disorders a vast amount of data from molecular genetic,
neurobiological, neuropsychological and psychosocial research has impressingly
confirmed this link for schizotypal personality disorder. Major research
deficits, however, have to be noticed for paranoid and schizoid personality
disorder.
PMID- 28699103
TI - Expansion of pathogen recognition specificity in plants using pattern recognition
receptors and artificially designed decoys.
AB - Pathogen/microbe-associated molecular patterns (PAMPs/MAMPs) are recognized by
plant pattern recognition receptors (PRRs) localized on the cell surface to
activate immune responses. This PAMP-triggered immunity (PTI) confers resistance
to a broad range of pathogenic microbes and, therefore, has a great potential for
genetically engineering broad-spectrum resistance by transferring PRRs across
plant families. Pathogenic effectors secreted by phytopathogens often directly
target and inhibit key components of PTI signaling pathways via diverse
biochemical mechanisms. In some cases, plants have evolved to produce decoy
proteins that mimic the direct virulence target, which senses the biochemical
activities of pathogenic effectors. This kind of perception traps the effectors
of erroneous targeting and results in the activation of effector-triggered
immunity (ETI) instead of suppressing PTI. This mechanism suggests that
artificially designed decoy proteins could be used to generate new recognition
specificities in a particular plant. In this review, we summarize recent advances
in research investigating PAMP recognition by PRRs and virulence effector
surveillance by decoy proteins. Successful expansion of recognition
specificities, conferred by the transgenic expression of EF-Tu receptor (EFR) and
AvrPphB susceptible 1 (PBS1) decoys, has highlighted the considerable potential
of PRRs and artificially designed decoys to expand plant resistance spectra and
the need to further identify novel PRRs and decoys.
PMID- 28699104
TI - Suprascapular nerve block for the treatment of hemiplegic shoulder pain in
patients with long-term chronic stroke: a pilot study.
AB - Hemiplegic shoulder pain is the most common pain condition after stroke.
Suprascapular nerve block is an effective treatment for shoulder pain. The aim of
this pilot study was to evaluate the effects of suprascapular nerve block on pain
intensity, spasticity, shoulder passive range of motion, and quality of life in
long-term chronic stroke patients with hemiplegic shoulder pain. Ten chronic
stroke patients (over 2 years from onset) with hemiplegic shoulder pain graded
>=30 mm on the Visual Analogue Scale underwent suprascapular nerve block
injection with 1 mL of 40 mg/mL methylprednisolone and 10 mL 0.5% bupivacaine
hydrochloride. Main outcome was the Visual Analogue Scale evaluated before and
after nerve block at 1 h, 1 week, and 1 month. Secondary outcomes were the
modified Ashworth scale and the shoulder elevation, abduction, and external
rotation passive range of motion evaluated before the nerve block and after 1 h
as well as the American Chronic Pain Association Quality of Life Scale evaluated
before and after nerve block at 1 month. The Visual Analogue Scale significantly
improved after nerve block at 1 h (P = 0.005) and 1 week (P = 0.011). Significant
improvements were found at 1 h after nerve block in the modified Ashworth scale
(P = 0.014) and the passive range of motion of shoulder abduction (P = 0.026),
flexion (P = 0.007), and external rotation (P = 0.017). The American Chronic Pain
Association Quality of Life Scale significantly improved at 1 month after nerve
block (P = 0.046). Our findings support the use of suprascapular nerve block for
treating hemiplegic shoulder pain in long-term chronic stroke patients.
PMID- 28699105
TI - Tapentadol in neuropathic pain cancer patients: a prospective open label study.
AB - Many chemotherapy treatments induce peripheral neuropathy (CIPN). These patients
often experience neuropathic pain (NP) that reduces the quality of life. The aim
of this prospective, open label study was to evaluate the efficacy and
tolerability of tapentadol (TP) in patients affected by CIPN. CIPN were
consecutively enrolled in a prospective open label study at the Neuro-Oncology
Unit of the Regina Elena National Cancer Institute in Rome. During the titration
phase, each patient initially received doses of TP 50 mg twice a day. All
patients underwent pain intensity (NRS) and DN4. For evaluation of quality of
life, patients underwent EORTC QLQ-C30 and EORTC QLQ-CIPN2 QLQ-CIPN20. We
enrolled 31 patients, 19 were females with a median age of 60 years. After 3
months of treatment with TP, 22 patients completed the statistical package for
social sciences (SPSS). Nineteen patients out of 22 showed a response to
treatment (86%). We also observed that TP reduced the NRS and DN4 values from
baseline to the last visit in a significant way (p < 0.001, respectively). Seven
patients (22.5%) discontinued the TP therapy after the first week of occurrence
of side effects. Furthermore, we observed that TP improved also the global health
status measured by EORT QLQ-C30. TP is well tolerated and efficacy in the
treatment of NP. The important reduction of neuropathic pain, the improvement in
NRS and QoL scores after therapy with TP makes it a candidate in the management
of patients suffering from neuropathic pain of CIPN also as a first line of
therapy.
PMID- 28699107
TI - Primary pure lymphoepithelioma-like carcinoma of the ureter.
PMID- 28699106
TI - Promoter Variant Alters Expression of the Autophagic BECN1 Gene: Implications for
Clinical Manifestations of Machado-Joseph Disease.
AB - Autophagy is especially important in disorders where accumulation of the mutant
protein is a hallmark, such as the Machado-Joseph disease/spinocerebellar ataxia
type 3 (MJD/SCA3). We analyzed the promoter of the BECN1 gene, whose
overexpression has been reported to exert neuroprotective effects in MJD, with
the aim of finding variants that could be associated with expression levels of
beclin-1 and could be tested as modifiers of onset and disease severity. A
fragment encompassing the BECN1 promoter was sequenced in 95 MJD subjects and 120
controls. The impact of the variation detected on transcription factors (TFs)
binding affinity was evaluated in silico and inferences concerning levels of
expression were confirmed by fluorescence-based quantitative real-time PCR in a
subset of 28 MJD subjects and 26 controls. Four previously described (rs60221525,
rs116943570, rs34882610, and rs34037822) and one novel (c.-933delG) variants were
identified. In silico analysis performed for the most frequent variants
rs60221525 C allele and rs116943570 T allele-predicted an impact of the presence
of these alleles on TF binding affinity. BECN1 expression levels were in
agreement with the in silico predictions, showing a tendency for decreased levels
in samples with the rs60221525 C allele and for increased levels in samples with
the rs116943570 T allele. MJD patients carrying the rs60221525 C allele presented
a tendency for earlier estimated age at onset. Moreover, patients with the
rs60221525 C allele presented a more severe clinical picture, compared to
patients without this allele. The analysis of a larger number of patients from
different cohorts, currently unavailable, would be required to confirm these
results.
PMID- 28699108
TI - The role of epithelial-mesenchymal transition in squamous cell carcinoma of the
oral cavity.
AB - Epithelial-mesenchymal transition (EMT) has emerged as a possible mechanism of
cancer metastasizing, but strong evidence for EMT involvement in human cancer is
lacking. Our aim was to compare oral spindle cell carcinoma (SpCC) as an example
of EMT with oral conventional squamous cell carcinoma (SCC) with and without
nodal metastases to test the hypothesis that EMT contributes to metastasizing in
oral SCC. Thirty cases of oral SCC with and without nodal metastasis and 15 cases
of SpCC were included. Epithelial (cytokeratin, E-cadherin), mesenchymal
(vimentin, N-cadherin), and stem cell markers (ALDH-1, CD44, Nanog, Sox-2) and
transcription repressors (Snail, Slug, Twist) were analyzed
immunohistochemically. We also analyzed the expression of microRNAs miR-141, miR
200 family, miR-205, and miR-429. SpCC exhibited loss of epithelial markers and
expression of mesenchymal markers or coexpression of both up-regulation of
transcription repressors and down-regulation of the investigated microRNAs. SCC
showed only occasional focal expression of mesenchymal markers at the invasive
front. No other differences were observed between SCC with and without nodal
metastases except for a higher expression of ALDH-1 in SCC with metastases. Our
results suggest that SpCC is an example of true EMT but do not support the
hypothesis that EMT is involved in metastasizing of conventional SCC. Regarding
oral SCC progression and metastasizing, we have been facing a shift from the
initial enthusiasm for the EMT concept towards a more critical approach with "EMT
like" and "partial EMT" concepts. The real question, though, is, is there no EMT
at all?
PMID- 28699109
TI - Malignant mesenchymal neoplasms of the dermis and subcutis mimicking benign
lesions: a case-based review.
AB - In this short review, malignant mesenchymal neoplasms of the dermis and subcutis
mimicking benign lesions and their differential diagnoses are discussed. These
include plaque-like dermatofibrosarcoma protuberans, superficial low-grade
fibromyxoid sarcoma, low-grade superficial malignant peripheral nerve sheath
tumour, epithelioid sarcoma, pseudomyogenic haemangioendothelioma, Kaposi sarcoma
mimicking cavernous haemangioma and benign lymphangioendothelioma, and rare forms
of angiosarcoma mimicking a benign vascular lesion.
PMID- 28699110
TI - Immune selection during tumor checkpoint inhibition therapy paves way for NK-cell
"missing self" recognition.
AB - The ability of NK cells to specifically recognize cells lacking expression of
self-MHC class I molecules was discovered over 30 years ago. It provided the
foundation for the "missing self" hypothesis. Research in the two past decades
has contributed to a detailed understanding of the molecular mechanisms that
determine the specificity and strength of NK cell-mediated "missing self"
responses to tumor cells. However, in light of the recent remarkable
breakthroughs in clinical cancer immunotherapy, the cytolytic potential of NK
cells still remains largely untapped in clinical settings. There is abundant
evidence demonstrating partial or complete loss of HLA class I expression in a
wide spectrum of human tumor types. Such loss may result from immune selection of
escape variants by tumor-specific CD8 T cells and has more recently also been
linked to acquired resistance to checkpoint inhibition therapy. In the present
review, we discuss the early predictions of the "missing self" hypothesis, its
molecular basis and outline the potential for NK cell-based adoptive
immunotherapy to convert checkpoint inhibitor therapy-resistant patients into
clinical responders.
PMID- 28699111
TI - HLA class Ib in pregnancy and pregnancy-related disorders.
AB - The HLA class Ib genes, HLA-E, HLA-F, and HLA-G, were discovered long after the
classical HLA class Ia genes. The elucidation of their functions had a modest
beginning. However, their basic functions and involvement in pathophysiology and
a range of diseases are now emerging. Although results from a range of studies
support the functional roles for the HLA class Ib molecules in adult life,
especially HLA-G and HLA-F have most intensively been, and were also primarily,
studied in relation to reproduction and pregnancy. The expression of HLA class Ib
proteins at the feto-maternal interface in the placenta seems to be important for
the maternal acceptance of the semi-allogenic fetus. In contrast to the functions
of HLA class Ia, HLA-G possesses immune-modulatory and tolerogenic functions.
Here, we review an accumulating amount of data describing the functions of HLA
class Ib molecules in relation to fertility, reproduction, and pregnancy, and a
possible role for these molecules in certain pregnancy complications, such as
implantation failure, recurrent spontaneous abortions, and pre-eclampsia. The
results from different kinds of studies point toward a role for HLA class Ib,
especially HLA-G, throughout the reproductive cycle from conception to the birth
weight of the child.
PMID- 28699112
TI - Brain Under Stress and Alzheimer's Disease.
AB - Modern society is characterized by the ubiquity of stressors that affect every
individual to different extents. Furthermore, experimental, clinical, and
epidemiological data have shown that chronic activation of the stress response
may participate in the development of various somatic as well as neuropsychiatric
diseases. Surprisingly, the role that stress plays in the etiopathogenesis of
Alzheimer's disease (AD) has not yet been studied in detail and is therefore not
well understood. However, accumulated data have shown that neuroendocrine and
behavioral changes accompanying the stress response affect neuronal homeostasis
and compromise several key neuronal processes. Mediators of the neuroendocrine
stress response, if elevated repeatedly or chronically, exert direct detrimental
effects on the brain by impairing neuronal metabolism, plasticity, and survival.
Stress-induced hormonal and behavioral reactions may also participate in the
development of hypertension, atherosclerosis, insulin resistance, and other
peripheral disturbances that may indirectly induce neuropathological processes
participating in the development and progression of AD. Importantly, stress
induced detrimental effects as etiological factors of AD are attractive because
they can be reduced by several approaches including behavioral and
pharmacological interventions. These interventions may therefore represent an
important strategy for prevention or attenuation of the progression of AD.
PMID- 28699113
TI - Protective Role Of Naringenin Against Abeta25-35-Caused Damage via ER and
PI3K/Akt-Mediated Pathways.
AB - Senile plaque accumulation and neurofibrillary tangles are primary
characteristics of Alzheimer's disease. We aimed to assess the protective
functions of naringenin against beta-amyloid protein fragment 25-35 (Abeta25-35)
caused nerve damage in differentiated PC12 cells, and study the potential
mechanisms. We evaluated cell viability and apoptosis using the 3-(4, 5
Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) test and flow
cytometry, respectively. Moreover, we measured protein kinase B (Akt), glycogen
synthase kinase-3beta (GSK-3beta), and caspase-3 activity via western blotting
and RT-PCR. We found that naringenin protected cell against Abeta25-35-caused
nerve damage by increasing cell viability, promoting Akt and GSK3beta activation,
and inhibiting cell apoptosis and caspase-3 activity. However, treatment with the
estrogen receptor (ER) antagonist ICI182, 780 or phosphatidylinositol-3-kinase
(PI3K) inhibitor LY294002 suppressed the effects of naringenin. Our results
suggested that naringenin could effectively suppress Abeta25-35-caused nerve
damage in PC12 cells by regulating the ER and PI3K/Akt pathways.
PMID- 28699114
TI - Reversible Hypokalemia and Bartter-Like Syndrome during Prolonged Systemic
Therapy with Colistimethate Sodium in an Adult Patient.
AB - We present the case of a 58-year-old woman who developed hypokalaemia and
metabolic alkalosis 2 weeks after therapy with colistimethate sodium for the
treatment of chronic lower limb ulcer infection by extensively drug-resistant
(XDR) Pseudomonas aeruginosa. The metabolic changes observed resembled Bartter
syndrome, a group of congenital disorders affecting the distal segments of the
renal tubules. The metabolic abnormalities reversed spontaneously 6 days after
drug discontinuation. Acquired forms of Bartter syndrome have been reported
during courses of antibiotic therapy; however, to our knowledge, this is the
first documented case associated with colistimethate therapy in an adult.
PMID- 28699115
TI - Non-cellulosic polysaccharide distribution during G-layer formation in poplar
tension wood fibers: abundance of rhamnogalacturonan I and arabinogalactan
proteins but no evidence of xyloglucan.
AB - MAIN CONCLUSION: RG-I and AGP, but not XG, are associated to the building of the
peculiar mechanical properties of tension wood. Hardwood trees produce tension
wood (TW) with specific mechanical properties to cope with environmental cues.
Poplar TW fibers have an additional cell wall layer, the G-layer responsible for
TW mechanical properties. We investigated, in two poplar hybrid species, the
molecules potentially involved in the building of TW mechanical properties.
First, we evaluated the distribution of the different classes of non-cellulosic
polysaccharides during xylem fiber differentiation, using immunolocalization. In
parallel, G-layers were isolated and their polysaccharide composition determined.
These complementary approaches provided information on the occurrence of non
cellulosic polysaccharides during G-fiber differentiation. We found no evidence
of the presence of xyloglucan (XG) in poplar G-layers, whereas arabinogalactan
proteins (AGP) and rhamnogalacturonan type I pectins (RG-I) were abundant, with
an apparent progressive loss of RG-I side chains during G-layer maturation.
Similarly, the intensity of immunolabeling signals specific for glucomannans and
glucuronoxylans varies during G-layer maturation. RG-I and AGP are best candidate
matrix components to be responsible for TW mechanical properties.
PMID- 28699116
TI - High taxonomic diversity of cultivation-recalcitrant endophytic bacteria in
grapevine field shoots, their in vitro introduction, and unsuspected persistence.
AB - MAIN CONCLUSION: Molecular and microscopic analyses reveal enormous non
cultivable endophytic bacteria in grapevine field shoots with functional
significance. Diverse bacteria enter tissue cultures through surface-sterilized
tissues and survive surreptitiously with varying taxonomic realignments. The
study was envisaged to assess the extent of endophytic bacterial association with
field shoot tissues of grapevine and the likelihood of introduction of such
internally colonizing bacteria in vitro adopting molecular techniques targeting
the non-cultivable bacterial community. PowerFood(r)-kit derived DNA from surface
sterilized field shoot tips of grapevine Flame Seedless was employed in a
preliminary bacterial class-specific PCR screening proving positive for major
prokaryotic taxa including Archaea. Taxonomic and functional diversity were
analyzed through whole metagenome profiling (WMG) which revealed predominantly
phylum Actinobacteria, Proteobacteria, and minor shares of Firmicutes,
Bacteroidetes, and Deinococcus-Thermus with varying functional roles ascribable
to the whole bacterial community. Field shoot tip tissues and callus derived from
stem segments were further employed in 16S rRNA V3-V4 amplicon taxonomic
profiling. This revealed elevated taxonomic diversity in field shoots over WMG,
predominantly Proteobacteria succeeded by Actinobacteria, Firmicutes,
Bacteroidetes, and 15 other phyla including several candidate phyla (135
families, 179 genera). Callus stocks also displayed broad bacterial diversity (16
phyla; 96 families; 141 genera) bearing resemblance to field tissues with
Proteobacterial dominance but a reduction in its share, enrichment of
Actinobacteria and Firmicutes, disappearance of some field-associated phyla and
detection of a few additional taxonomic groups over field community. Similar
results were documented during 16S V3-V4 amplicon taxonomic profiling on Thompson
Seedless field shoot tip and callus tissues. Video microscopy on tissue
homogenates corroborated enormous endophytic bacteria. This study elucidates a
vast diversity of cultivation-recalcitrant endophytic bacteria prevailing in
grapevine field shoots, their in vitro introduction, and unsuspecting sustenance
with possible silent participation in tissue culture processes.
PMID- 28699117
TI - Determination of total mercury in aluminium industrial zones and soil
contaminated with red mud.
AB - This study investigated total mercury contents in areas impacted by aluminium
plants in Tajikistan and Slovakia and in one area flooded with red mud in
Hungary. We present the first determination of total mercury contents in the near
top soil (0-10 and 10-20 cm) in Tajikistan and the first comparative
investigation of Tajikistan-Slovakia-Hungary. The Tajik Aluminium Company (TALCO)
is one of the leading producers of primary aluminium in Central Asia. In the past
30 years, the plant has been producing large volumes of industrial waste,
resulting in negative impacts on soil, groundwater and air quality of the
surrounding region. Mercury concentrations were significant in Slovakia and
Hungary, 6 years after the flooding. In studied areas in Slovakia and Hungary,
concentrations of total mercury exceeded the threshold limit value (TLV = 0.5 mg
Hg kg-1). However, in Tajikistan, values were below the TLV (0.006-0.074 mg kg-1)
and did not significantly vary between depths. Total Hg in Slovakia ranged from
0.057 to 0.668 mg kg-1 and in Hungary from 0.029 to 1.275 mg kg-1. However, in
the plots near to the red mud reservoir and the flooded area, Hg concentrations
were higher in the upper layers than in the lower ones.
PMID- 28699118
TI - Fractionation of trace elements and human health risk of submicron particulate
matter (PM1) collected in the surroundings of coking plants.
AB - Samples of PM1 were collected in the surroundings of coking plants located in
southern Poland. Chemical fractionation provided information on the contents of
trace elements As, Cd, Co, Cr, Hg, Mn, Ni, Pb, Sb and Se in all mobile (F1-F3)
and not mobile (F4) fractions of PM1 in the vicinity of large sources of
emissions related to energochemical processing of coal during the summer. The
determined enrichment factors indicate the influence of anthropogenic sources on
the concentration of the examined elements contained in PM1 in the areas
subjected to investigation. The analysis of health risk for the assumed scenario
of inhabitant exposure to the toxic effect of elements, based on the values of
the hazard index, revealed that the absorption of the examined elements contained
in the most mobile fractions of particulate matter via inhalation by children and
adults can be considered potentially harmless to the health of people inhabiting
the surroundings of coking plants during the summer (HI < 1). It has been
estimated that due to the inhalation exposure to carcinogenic elements, i.e., As,
Cd, Co, Cr, Ni and Pb, contained in the most mobile fractions (F1 + F2) of PM1,
approximately four adults and one child out of one million people living in the
vicinity of the coking plants may develop cancer.
PMID- 28699119
TI - Deposited atmospheric dust as influenced by anthropogenic emissions in northern
China.
AB - Atmospheric particulate matter (PM) from multinatural and anthropogenic sources
poses serious risk to human health and contaminates soil and water resources as
it settles back to ground environment and ecosystem. In this study, dust
deposition flux (DDF), pollution load index (PLI) of heavy metals, enrichment
factor (EF), and settling flux (SF) of eighteen chemical elements were
investigated in comparison with crustal composition to assess the influence of
anthropogenic emission on PM in major northern Chinese cities. The annual DDF in
Lanzhou, Huhhot, Beijing, Zhengzhou, and Harbin was 134.7, 240.6, 103.7, 124.7,
and 196.7 g m-2, respectively. The annual EF of Zn in Harbin, Cd in Lanzhou, and
Cd in Beijing was 736.4, 248.6, and 166.3, respectively. Most of the inspected
elements were enriched during winter in Lanzhou. Annual PLI showed that deposited
dust in Beijing had the highest concentration of heavy metals. Seasonal PLI
exhibited obvious changes in different cities. The annual SF of crustal elements
was 1-5 orders higher than that of heavy metals. The highest annual SF of
elements was identified mainly in Lanzhou and Huhhot. Sulfur, cadmium, copper,
lead, and zinc in the dustfall of most urban areas were from human activities.
Fossil fuel burning, metal smelting, mining, construction, and vehicle exhaust
are the major sources of enriched elements in dustfall in urban areas of northern
China. Toxic pollutants with dustfall are widespread and persistent, which
deserves public concern in future sustainable development.
PMID- 28699120
TI - Valve-related modes of pump failure in collecting lymphatics: numerical and
experimental investigation.
AB - Lymph is transported along collecting lymphatic vessels by intrinsic and
extrinsic pumping. The walls have muscle of a type intermediate between blood
vascular smooth muscle and myocardium; a contracting segment between two valves
(a lymphangion) constitutes a pump. This intrinsic mechanism is investigated ex
vivo in isolated, spontaneously contracting, perfused segments subjected to
controlled external pressures. The reaction to varying afterload is probed by
slowly ramping up the outlet pressure until pumping fails. Often the failure
occurs when the contraction raises intra-lymphangion pressure insufficiently to
overcome the outlet pressure, open the outlet valve and cause ejection, but many
segments fail by other means, the mechanisms of which are not clear. We here
elucidate those mechanisms by resort to a numerical model. Experimental
observations are paired with comparable findings from computer simulations, using
a lumped-parameter model that incorporates previously measured valve properties,
plus new measurements of active contractile and passive elastic properties, and
the dependence of contraction frequency on transmural pressure, all taken from
isobaric twitch contraction experiments in the same vessel. Surprisingly, the
model predicts seven different possible modes of pump failure, each defined by a
different sequence of valve events, with their occurrence depending on the
parameter values and boundary conditions. Some, but not all, modes were found
experimentally. Further model investigation reveals routes by which a vessel
exhibiting one mode of failure might under altered circumstances exhibit another.
PMID- 28699121
TI - Friendship Dynamics of Adolescent Aggression, Prosocial Behavior, and Social
Status: The Moderating Role of Gender.
AB - Interactions with friends are a salient part of adolescents' experience at
school. Adolescents tend to form friendships with similar peers and, in turn,
their friends influence adolescents' behaviors and beliefs. The current study
investigated early adolescents' selection of friends and friends' influence with
regard to physical aggression, prosocial behavior, and popularity and social
preference (i.e., likeability) among fifth and sixth graders (N = 736, 52% girls
at wave1, N = 677, 52% girls at wave 2) in elementary schools in South Korea. The
moderating role of gender on early adolescents' friend selection and influence
was also examined. With longitudinal social network analysis (RSiena), we found
that youth tended to select friends with similar levels of physical aggression
and popularity, and their friends influenced their own physical aggression and
popularity over time. The higher youth were in social preference, the less likely
they chose physically aggressive peers as friends. Boys were more likely to
select highly popular peers as friends compared to girls, and influence effects
for physical aggression and popularity were stronger for boys compared to girls.
The results underscore the importance of gender in friendship dynamics among
Asian early adolescents.
PMID- 28699122
TI - Improved information pooling for hierarchical cognitive models through multiple
and covaried regression.
AB - Cognitive process models are fit to observed data to infer how experimental
manipulations modify the assumed underlying cognitive process. They are
alternatives to descriptive models, which only capture differences on the
observed data level, and do not make assumptions about the underlying cognitive
process. Process models may require more observations than descriptive models
however, and as a consequence, usually fewer conditions can be simultaneously
modeled with them. Unfortunately, it is known that the predictive validity of a
model may be compromised when fewer experimental conditions are jointly accounted
for (e.g., overestimation of predictor effects, or their incorrect assignment).
We develop a hierarchical and covaried multiple regression approach to address
this problem. Specifically, we show how to map the recurrences of all conditions,
participants, items, and/or traits across experimental design cells to the
process model parameters. This systematic pooling of information can facilitate
parameter estimation. The proposed approach is particularly relevant for multi
factor experimental designs, and for mixture models that parameterize per cell to
assess predictor effects. This hierarchical framework provides the capacity to
model more conditions jointly to improve parameter recovery at low observation
numbers (e.g., using only 1/6 of trials, recovering as well as standard
hierarchical Bayesian methods), and to directly model predictor and covariate
effects on the process parameters, without the need for post hoc analyses (e.g.,
ANOVA). An example application to real data is also provided.
PMID- 28699123
TI - The tool for the automatic analysis of lexical sophistication (TAALES): version
2.0.
AB - This study introduces the second release of the Tool for the Automatic Analysis
of Lexical Sophistication (TAALES 2.0), a freely available and easy-to-use text
analysis tool. TAALES 2.0 is housed on a user's hard drive (allowing for secure
data processing) and is available on most operating systems (Windows, Mac, and
Linux). TAALES 2.0 adds 316 indices to the original tool. These indices are
related to word frequency, word range, n-gram frequency, n-gram range, n-gram
strength of association, contextual distinctiveness, word recognition norms,
semantic network, and word neighbors. In this study, we validated TAALES 2.0 by
investigating whether its indices could be used to model both holistic scores of
lexical proficiency in free writes and word choice scores in narrative essays.
The results indicated that the TAALES 2.0 indices could be used to explain 58% of
the variance in lexical proficiency scores and 32% of the variance in word-choice
scores. Newly added TAALES 2.0 indices, including those related to n-gram
association strength, word neighborhood, and word recognition norms, featured
heavily in these predictor models, suggesting that TAALES 2.0 represents a
substantial upgrade.
PMID- 28699124
TI - Conversation level syntax similarity metric.
AB - The syntax and semantics of human language can illuminate many individual
psychological differences and important dimensions of social interaction.
Accordingly, psychological and psycholinguistic research has begun incorporating
sophisticated representations of semantic content to better understand the
connection between word choice and psychological processes. In this work we
introduce ConversAtion level Syntax SImilarity Metric (CASSIM), a novel method
for calculating conversation-level syntax similarity. CASSIM estimates the syntax
similarity between conversations by automatically generating syntactical
representations of the sentences in conversation, estimating the structural
differences between them, and calculating an optimized estimate of the
conversation-level syntax similarity. After introducing and explaining this
method, we report results from two method validation experiments (Study 1) and
conduct a series of analyses with CASSIM to investigate syntax accommodation in
social media discourse (Study 2). We run the same experiments using two well
known existing syntactic metrics, LSM and Coh-Metrix, and compare their results
to CASSIM. Overall, our results indicate that CASSIM is able to reliably measure
syntax similarity and to provide robust evidence of syntax accommodation within
social media discourse.
PMID- 28699125
TI - Uptake of Predictive Genetic Testing and Cardiac Evaluation for Children at Risk
for an Inherited Arrhythmia or Cardiomyopathy.
AB - Predictive genetic testing in minors should be considered when clinical
intervention is available. Children who carry a pathogenic variant for an
inherited arrhythmia or cardiomyopathy require regular cardiac screening and may
be prescribed medication and/or be told to modify their physical activity.
Medical genetics and pediatric cardiology charts were reviewed to identify
factors associated with uptake of genetic testing and cardiac evaluation for
children at risk for long QT syndrome, hypertrophic cardiomyopathy or
arrhythmogenic right ventricular cardiomyopathy. The data collected included
genetic diagnosis, clinical symptoms in the carrier parent, number of children
under 18 years of age, age of children, family history of sudden cardiac
arrest/death, uptake of cardiac evaluation and if evaluated, phenotype for each
child. We identified 97 at risk children from 58 families found to carry a
pathogenic variant for one of these conditions. Sixty six percent of the families
pursued genetic testing and 73% underwent cardiac screening when it was
recommended. Declining predictive genetic testing was significantly associated
with genetic specialist recommendation (p < 0.001) and having an asymptomatic
carrier father (p = 0.006). Cardiac evaluation was significantly associated with
uptake of genetic testing (p = 0.007). This study provides a greater
understanding of factors associated with uptake of genetic testing and cardiac
evaluation in children at risk of an inherited arrhythmia or cardiomyopathy. It
also identifies a need to educate families about the importance of cardiac
evaluation even in the absence of genetic testing.
PMID- 28699126
TI - A Report on Ten Asia Pacific Countries on Current Status and Future Directions of
the Genetic Counseling Profession: The Establishment of the Professional Society
of Genetic Counselors in Asia.
AB - The Professional Society of Genetic Counselors in Asia (PSGCA) was recently
established as a special interest group of the Asia Pacific Society of Human
Genetics. Fostering partnerships across the globe, the PSGCA's vision is to be
the lead organization that advances and mainstreams the genetic counseling
profession in Asia and ensures individuals have access to genetic counseling
services. Its mission is to promote quality genetic counseling services in the
region by enhancing practice and curricular standards, research and continuing
education. The PSGCA was formally launched during the Genetic Counseling Pre
Conference Workshop held at the 11th Asia-Pacific Conference on Human Genetics in
Hanoi, Viet Nam, September 16, 2015. The pre-conference workshop provided an
opportunity for medical geneticists and genetic counselors from across 10 Asia
Pacific countries to learn about the varied genetic counseling practices and
strategies for genetic counseling training. This paper provides an overview of
the current status and challenges in these countries, and proposed course of
unified actions for the future of the genetic counseling profession.
PMID- 28699127
TI - Erratum to: Semisynthesis and biological evaluation of prenylated resveratrol
derivatives as multi-targeted agents for Alzheimer's disease.
PMID- 28699128
TI - Structures of antimutagenic constituents in the peels of Citrus limon.
AB - The methanolic extracts from the peels of Citrus limon were found to show
antimutagenic effects against 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole, and 2
amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in the Ames test. From the
methanolic extracts, four new coumarins (wakayamalimonol A-D) and a new
furanocoumarin (wakayamalimonol E) were isolated together with fifteen known
compounds. The absolute stereostructures of the new compounds were determined by
chemical synthesis and the modified Mosher's method. Among the isolated
constituents, coumarins, furanocoumarins, and limonoids showed antimutagenic
effects in the Ames test. One of the major constituent, limonin, showed
significant antimutagenic effects against mitomycinC and PhIP in the micronucleus
test in vivo.
PMID- 28699129
TI - Shikonin changes the lipopolysaccharide-induced expression of inflammation
related genes in macrophages.
AB - We aimed to find candidate molecules possibly involved in the anti-inflammatory
activity of shikonin (active compound of "Shikon") by analyzing its effects on
gene expression of lipopolysaccharide (LPS)-treated THP-1 macrophages. Polysome
associated mRNAs (those expected to be under translation: translatome) from cells
treated with LPS alone (LPS: 5 ug/mL), shikonin alone (S: 100 nM), or LPS plus
shikonin (LPS&S) for 3 h were analyzed by DNA microarray followed by detection of
enriched pathways/gene ontologies using the tools of the STRING database.
Candidate genes in enriched pathways in the comparison of LPS&S cells vs. LPS
cells were analyzed by reverse-transcription quantitative real-time PCR (RT-qPCR;
1, 2, and 3 h). DNA microarray showed shikonin significantly influences gene
expression. Gene expression changes between LPS&S cells and LPS cells were
compared to detect relevant proteins and/or mRNAs underlying its anti
inflammatory effects: shikonin downregulated pathways which were upregulated in
LPS cells, for example, 'innate immune response'. Within changed pathways, three
genes were selected for RT-qPCR analyses as key candidates influencing
inflammatory responses: CYBA (component of the superoxide-generating Nox2
enzyme), GSK3B (controller of cell responses after toll-like receptor
stimulation), and EIF4E (a key factor of the eukaryotic translation initiation
factor 4F complex that regulates abundance of other proteins involved in immune
functions). All three mRNAs were decreased at 2 h, and CYBA continued low at 3 h
relative to LPS cells. Given that shikonin decreased the expression of CYBA gene
of Nox2, in addition to the direct inhibition of the Nox2 activity that we have
previously shown, it is suggested that one of its anti-inflammatory mechanisms
could be attenuation of oxidative stress.
PMID- 28699130
TI - Cost Effectiveness of Risk-Reducing Mastectomy versus Surveillance in BRCA
Mutation Carriers with a History of Ovarian Cancer.
AB - BACKGROUND: The appropriate management of breast cancer risk in BRCA mutation
carriers following ovarian cancer diagnosis remains unclear. We sought to
determine the survival benefit and cost effectiveness of risk-reducing mastectomy
(RRM) among women with BRCA1/2 mutations following stage II-IV ovarian cancer.
DESIGN: We constructed a decision model from a third-party payer perspective to
compare annual screening with magnetic resonance imaging (MRI) and mammography to
annual screening followed by RRM with reconstruction following ovarian cancer
diagnosis. Survival, overall costs, and cost effectiveness were determined by
decade at diagnosis using 2015 US dollars. All inputs were obtained from the
literature and public databases. Monte Carlo probabilistic sensitivity analysis
was performed with a $100,000 willingness-to-pay threshold. RESULTS: The
incremental cost-effectiveness ratio (ICER) per year of life saved (YLS) for RRM
increased with age and BRCA2 mutation status, with greater survival benefit
demonstrated in younger patients with BRCA1 mutations. RRM delayed 5 years in 40
year-old BRCA1 mutation carriers was associated with 5 months of life gained
(ICER $72,739/YLS), and in 60-year-old BRCA2 mutation carriers was associated
with 0.8 months of life gained (ICER $334,906/YLS). In all scenarios, $/YLS and
mastectomies per breast cancer prevented were lowest with RRM performed 5-10
years after ovarian cancer diagnosis. CONCLUSION: For most BRCA1/2 mutation
carriers following ovarian cancer diagnosis, RRM performed within 5 years is not
cost effective when compared with breast cancer screening. Imaging surveillance
should be advocated during the first several years after ovarian cancer
diagnosis, after which point the benefits of RRM can be considered based on
patient age and BRCA mutation status.
PMID- 28699131
TI - "Pancreas-Compressionless Gastrectomy": A Novel Laparoscopic Approach for
Suprapancreatic Lymph Node Dissection.
AB - BACKGROUND: In radical operations for gastric cancer, a balance between the
quality of lymph node dissection and safety of surgery must be ensured. During
suprapancreatic lymphadenectomy in laparoscopic gastrectomy (LG), an adequate
operative field should be safely and effectively established to reduce pancreas
related complications. We present a novel approach that avoids direct compression
of the pancreas in LG and describe the surgical outcomes of this method. METHODS:
We historically compressed the pancreas during suprapancreatic lymph node
dissection in LG to obtain an adequate operative field but have since modified
our operative technique. In our new method introduced in March 2016, the
operative field is established by pulling and controlling the connective tissues
along the inferior border of the pancreas and the nerves along the common hepatic
and splenic arteries, instead of directly compressing the pancreas itself. We
compared 51 patients in the compression group (January 2015-February 2016) and 45
patients in the compressionless group (March 2016-January 2017) in terms of
surgical outcomes, including the amylase concentration in the drainage fluid and
postoperative complications. RESULTS: The amylase concentrations in the
compressionless group were significantly lower on postoperative days 1 and 3 (p <
0.001 and p = 0.013, respectively) compared with the compression group. The rates
of severe postoperative pancreatic fistula and intra-abdominal infectious
complications decreased from 11.8 to 2.2% (p = 0.116) and from 17.6 and 2.2% (p =
0.018), respectively. CONCLUSIONS: Our approach, termed "pancreas-compressionless
gastrectomy," can be considered a safe and useful method to prevent postoperative
infectious complications in LG.
PMID- 28699132
TI - Effects of Preoperative Malnutrition on Short- and Long-Term Outcomes of Patients
with Gastric Cancer: Can We Do Better?
AB - BACKGROUND: The effects of preoperative malnutrition and preoperative correction
of hypoalbuminemia (PCH) on the short- and long-term outcomes in patients with
gastric cancer are unclear. OBJECTIVE: This study aimed to examine the effect of
preoperative nutritional status on short- and long-term outcomes in patients who
underwent radical gastrectomy, and also explored the role of PCH in malnourished
patients with gastric cancer. METHODS: We prospectively reviewed data from
patients with gastric cancer who were treated in our department between January
2009 and December 2014. The effect of preoperative nutritional status on short-
and long-term outcomes in patients who underwent radical gastrectomy was
investigated, and we explored whether PCH could improve the short- and long-term
outcomes of these patients. RESULTS: A total of 1976 patients were analyzed,
including 412 patients in the malnourished group and 1564 in the well-nourished
group. The overall incidence of complications in the malnourished group was
significantly higher than the well-nourished group (21.4 vs. 15.5%, p = 0.005).
Except for incision infection (3.2 vs. 1.6%, p = 0.041), there were no
significant differences for other complications. In the malnourished group, 98
cases of preoperative hypoproteinemia were corrected (PCH group), whereas 314
cases were not (NPCH group). The incidence of incision infection in the PCH group
was significantly lower than in the NPCH group (0 vs. 4.1%, p = 0.041). The
median follow-up time was 39 months (1.0-88.0 months), and the 3-year overall
survival (OS; 59.1 vs. 75%, p < 0.001) and disease-free survival (DFS; 54.8 vs.
72.5%, p < 0.001) rates were significantly lower in the malnourished group than
in the well-nourished group. A multivariate Cox regression analysis showed that
malnutrition was an independent prognostic factor for 3-year OS (hazard ratio
[HR] 1.211, 95% confidence interval [CI] 1.01-1.452, p = 0.039) and DFS (HR
1.168, 95% CI 1.013-1.398, p = 0.043). For the malnourished group with stage I
gastric cancer, the PCH and NPCH groups showed no significant differences in 3
year OS (90.0 vs. 89.0%, p = 0.227) or DFS (90.0 vs. 87.3%, p = 0.363); however,
for the malnourished group with stages II-III gastric cancer, the 3-year OS (69.9
vs. 47.6%, p = 0.013) and DFS (55.4 vs. 43.6%, p = 0.046) rates were
significantly higher in the PCH group than in the NPCH group. CONCLUSIONS: The
incidence of incision infection was significantly higher in patients with
malnutrition than in well-nourished patients. The 3-year OS and DFS rates were
significantly lower in malnourished patients than in well-nourished patients. PCH
may both reduce the incidence of incisional infection in patients with
malnutrition and improve 3-year OS and DFS rates for malnourished patients with
stages II-III gastric cancer; however, to confirm our findings, further studies
are warranted.
PMID- 28699133
TI - Survival Rates for Patients with Resected Gastric Adenocarcinoma Finally have
Increased in the United States.
AB - BACKGROUND: In the United States, the overall survival rates for gastric
adenocarcinoma have remained low, with surgical resection as the only therapy for
many patients. Given the advances in multimodality treatment and the development
of guidelines recommending adequate lymph node evaluation, the authors determined
whether overall survival rates for patients with gastric adenocarcinoma have
increased in the United States. METHODS: The study used the Surveillance
Epidemiology and End Results (SEER) database to examine overall survival for
patients with the diagnosis of gastric adenocarcinoma between 1988 and 2013. The
study cohort was divided into five periods: 1988-1992, 1993-1997, 1998-2002, 2003
2007, and 2008-2013. Kaplan-Meier methods and Cox proportional hazards modeling
were used to determine the effect that year of diagnosis had on overall survival.
RESULTS: The diagnosis was determined for 13,470 patients between 1988 and 2013.
The use of radiation therapy and the proportion of patients who had at least 15
lymph nodes evaluated significantly increased during the study period. Unadjusted
Kaplan-Meier estimates demonstrated significantly better survival rates for the
patients with a diagnosis of gastric cancer in the later periods (2003-2007 and
2008-2013) than for those in the three earlier periods. In our Cox proportional
hazards model, recent period was associated with a significantly lower hazard of
5-year mortality. CONCLUSION: This analysis demonstrated for the first time that
gastric cancer survival rates have significantly improved in the United States
during the past 2 decades. This observation likely reflects improved adherence to
cancer treatment guidelines, including adequate lymph node evaluation and
delivery of adjuvant treatment more consistently.
PMID- 28699135
TI - 6th Annual Meeting Frontiers in Neurology 2016.
PMID- 28699134
TI - Intraoperative Tumor Detection Using a Ratiometric Activatable Fluorescent
Peptide: A First-in-Human Phase 1 Study.
AB - BACKGROUND: Positive surgical margins remain a significant challenge in breast
cancer surgery. This report describes the use of a novel, first-in-human
ratiometric activatable cell-penetrating peptide in breast cancer surgery.
METHODS: A two-part, multi-institutional phase 1 trial of AVB-620 with a 3+3 dose
escalation and dose-expansion cohorts was conducted. The patients received an
infusion of AVB-620 2-20 h before planned lumpectomy/mastectomy and sentinel node
biopsy/axillary dissection. Imaging analysis was performed on images obtained
from the surgical field as well as post-excision surgical specimens. Pathology
reports were obtained to correlate imaging results with histopathologic data.
Information on physical adverse events and laboratory abnormalities were
recorded. RESULTS: A total of 27 patients received infusion of AVB-620 and
underwent surgical excision of breast cancer. The findings showed no adverse
events or laboratory values attributable to infusion of AVB-620. The 8-mg dose
was selected from the dose-escalation cohort for use with the expansion cohort
based on imaging data. Region-of-interest (ROI) imaging analysis from the 8-mg
cohort demonstrated measurable changes between pathology confirmed tumor-positive
and tumor-negative tissue. CONCLUSION: Intraoperative imaging of surgical
specimens after infusion with AVB-620 allowed for real-time tumor detection.
Infusion of AVB-620 is safe and may improve intraoperative detection of malignant
tissue during breast cancer operations.
PMID- 28699136
TI - Intrawound application of vancomycin changes the responsible germ in elective
spine surgery without significant effect on the rate of infection: a randomized
prospective study.
AB - PURPOSE: Surgical site infection (SSI) is a costly complication associated with
spine surgery. The impact of intrawound vancomycin has not been strongly
postulated to decrease the risk of surgical site infection. We designed study to
determine whether intrawound vancomycin application reduces the risk of SSI in
patients after spine surgery. METHODS: A prospective randomized control trial
study to evaluate the patients with elective spine surgery in a period of 15
month was designed. Patients were divided into two groups based on whether
intrawound vancomycin was applied or not. The relative risk of SSI within
postoperative 30 days was evaluated. RESULTS: Three hundred and eighty patients
were included in this study: degenerative spine pathologies and tumor 80% (304),
trauma 11% (42) and deformity 9% (34). Intrawound vancomycin was used in 51% of
patients. Prevalence of SSI was 2.7% in the absence of vancomycin use versus 5.2%
with intrawound vancomycin. In multivariable regression model, those with higher
number of levels exposed, postoperative ICU admission and obesity and use of
instrumentation more than two levels had higher risk of developing SSI. In the
treatment group Acinetobacter and Pseudomonas aeruginosa (20%) were the most
common pathogens. In control group, Staphylococcus aureus and Acinetobacter (40%)
were the most common organisms. CONCLUSIONS: Intrawound application of vancomycin
after elective spine surgery was not associated with reduced risk of SSI and
return to OR associated with SSI in our patients. However, the use of intrawound
vancomycin changed the responsible infection germ.
PMID- 28699137
TI - Erratum to: Hepatopancreatic cells of a stone crab Menippe frontalis from Peru:
separation, viability study, and evaluation of lipoperoxidation against cadmium
contamination.
PMID- 28699138
TI - Toxicity, membrane binding and uptake of the Sclerotinia sclerotiorum agglutinin
(SSA) in different insect cell lines.
AB - The fungal lectin purified from Sclerotinia sclerotiorum, further referred to as
Sclerotinia sclerotiorum agglutinin or SSA, possesses insecticidal activity
against important pest insects such as pea aphids (Acyrthosiphon pisum). This
paper aims at a better understanding of its activity at cellular level.
Therefore, different insect cell lines were treated with SSA. These cell lines
were derived from different tissues and represent the three major orders of
insects important in agriculture: CF-203 (midgut Choristoneura fumiferana,
Lepidoptera), GUTAW1 (midgut, Helicoverpa zea, Lepidoptera), High5 cells (ovary,
Trichoplusia ni, Lepidoptera), Sf9 (ovary cells from Spodoptera frugiperda,
Lepidoptera), S2 (hemocyte, Drosophila melanogaster, Diptera), and TcA (whole
body, Tribolium castaneum, Coleoptera). Although the sensitivity to SSA differs
between the cell lines, SSA clearly showed toxicity in all six cell lines with
median effect concentrations (EC50) ranging between 9 and 42 MUg/ml. An in-depth
analysis of the mechanism of uptake in the cells revealed superior amounts of
FITC-SSA at the membrane of CF-203 cells compared to Sf9 cells, while a similar
small amount of SSA was internalized in both cell lines. Pre-incubation with the
clathrin-mediated endocytosis inhibitor phenylarsine oxide inhibited the
internalization of SSA into the CF-203 and Sf9 cells with a respective reduction
of 6- and 1.7-fold. The data are discussed in relation to the importance of
cellular uptake mechanism for SSA binding and cytotoxicity.
PMID- 28699139
TI - Response to comments on "Effects of different omega-3 sources, fish oil, krill
oil, and green-lipped mussel, against cytokine-mediated canine cartilage
degradation"-In Vitro Cell Dev Biol Anim. 2017 doi: 10.1007/s11626-016-0125-y.
PMID- 28699140
TI - Effects of different Sertoli cell types on the maintenance of adult
spermatogonial stem cells in vitro.
AB - Spermatongonial stem cells (SSCs) are unique testis cells that are able to
proliferate, differentiate, and transmit genetic information to the next
generation. However, the effect of different Sertoli cell types on the expression
of specific SSC genes is not yet well understood. In this study, we compare the
in vitro effect of adult Sertoli cells, embryonic Sertoli cells, and TM4 (a
Sertoli cell line) as feeder layers on the expression of SSC genes. SSCs were
isolated from the testis of adult male mice and purified by differential plating.
Following enrichment, SSCs were cultivated for 1 and 2 wk in the presence of
various feeders. The expression of SSC-specific genes (Mvh, ZBTB, and c-kit) was
evaluated by real-time polymerase chain reaction. Our results revealed that
expression of the specific SSC genes was significantly higher in the embryonic
Sertoli cells after 1 and 2 wk compared to the adult Sertoli cells and the TM4
group. Our finding suggest that co-culturing of SSCs with embryonic Sertoli cells
is helpful for in vitro cultivation of SSCs and might improve the self-renewal of
these stem cells.
PMID- 28699141
TI - Epi/perineural and Schwann Cells as Well as Perineural Sheath Integrity are
Affected Following 2,4-D Exposure.
AB - 2,4-dicholorophenoxy acetic acid (2,4-D) is a worldwide-known hormone herbicide.
However, there are increasing concerns about its exposure and risks of developing
pathological conditions for the peripheral nervous system. The aim of this study
was to investigate the mechanism(s) involved in the toxicity of 2,4-D on
peripheral nerve's cellular components. The epi/perineural and Schwann cells and
a total of three cell lines were treated with 2,4-D. The viability of cells at
different doses of 2,4-D was measured by MTT assay. The cell cycle analyses,
cumulative cell counting, fluorescent staining, antioxidant and caspase enzymes
activity were examined on epi/perineural and Schwann cells. The epi/perineural
cells were assessed as having biological macromolecular changes. Some tight
junction-related genes and proteins were also tested on explants of 2,4-D treated
epi/perineural tissue. The viability of 2,4-D treated cells was reduced in a dose
dependent manner. Reduced growth rate and G1 cell cycle arrest were verified in
2,4-D treated epi/perineural and Schwann cells. The use of staining methods
(acridine orange/ethidium bromide and DAPI) and caspase 3/7 activity assay along
with malondialdehyde, glutathione peroxidase, and superoxide dismutase activity
assays indicated the apoptotic and oxidant effects of 2,4-D on epi/perineural and
Schwann cells. Data obtained from FTIR revealed changes in epi/perineural
proteins and cell membrane lipids. Additionally, claudin-1, occludin, and ZO-1
gene/protein expression profiles were significantly reduced in 2,4-D-treated
epi/perineural pieces. Our data indicated that oxidative stress, apoptosis of
epi/perineural and Schwann cell and impaired blood-nerve barrier may have
contributed to nerve damage following 2,4-D exposure.
PMID- 28699142
TI - Bringing color to emotion: The influence of color on attentional bias to briefly
presented emotional images.
AB - Is color a critical feature in emotional content extraction and involuntary
attentional orienting toward affective stimuli? Here we used briefly presented
emotional distractors to investigate the extent to which color information can
influence the time course of attentional bias in early visual cortex. While
participants performed a demanding visual foreground task, complex unpleasant and
neutral background images were displayed in color or grayscale format for a short
period of 133 ms and were immediately masked. Such a short presentation poses a
challenge for visual processing. In the visual detection task, participants
attended to flickering squares that elicited the steady-state visual evoked
potential (SSVEP), allowing us to analyze the temporal dynamics of the
competition for processing resources in early visual cortex. Concurrently we
measured the visual event-related potentials (ERPs) evoked by the unpleasant and
neutral background scenes. The results showed (a) that the distraction effect was
greater with color than with grayscale images and (b) that it lasted longer with
colored unpleasant distractor images. Furthermore, classical and mass-univariate
ERP analyses indicated that, when presented in color, emotional scenes elicited
more pronounced early negativities (N1-EPN) relative to neutral scenes, than when
the scenes were presented in grayscale. Consistent with neural data, unpleasant
scenes were rated as being more emotionally negative and received slightly higher
arousal values when they were shown in color than when they were presented in
grayscale. Taken together, these findings provide evidence for the modulatory
role of picture color on a cascade of coordinated perceptual processes: by
facilitating the higher-level extraction of emotional content, color influences
the duration of the attentional bias to briefly presented affective scenes in
lower-tier visual areas.
PMID- 28699143
TI - Glutaric Aciduria Type 1 and Acute Renal Failure: Case Report and Suggested
Pathomechanisms.
AB - Glutaric aciduria type 1 (GA1) is caused by deficiency of the mitochondrial
matrix enzyme glutaryl-CoA dehydrogenase (GCDH), leading to accumulation of
glutaric acid (GA) and 3-hydroxyglutaric acid (3OHGA) in tissues and body fluids.
During catabolic crises, GA1 patients are prone to the development of striatal
necrosis and a subsequent irreversible movement disorder during a time window of
vulnerability in early infancy. Thus, GA1 had been considered a pure "cerebral
organic aciduria" in the past. Single case reports have indicated the occurrence
of acute renal dysfunction in children affected by GA1. In addition, growing
evidence arises that GA1 patients may develop chronic renal failure during
adulthood independent of the previous occurrence of encephalopathic crises. The
underlying mechanisms are yet unknown. Here we report on a 3-year-old GA1 patient
who died following the development of acute renal failure most likely due to
haemolytic uraemic syndrome associated with a pneumococcal infection. We
hypothesise that known GA1 pathomechanisms, namely the endothelial dysfunction
mediated by 3OHGA, as well as the transporter mechanisms for the urinary
excretion of GA and 3OHGA, are involved in the development of glomerular and
tubular dysfunction, respectively, and may contribute to a pre-disposition of GA1
patients to renal disease. We recommend careful differential monitoring of
glomerular and tubular renal function in GA1 patients.
PMID- 28699144
TI - Palliative Care Needs Assessment in the Neuro-ICU: Effect on Family.
AB - BACKGROUND: Examine the association of a daily palliative care needs checklist on
outcomes for family members of patients discharged from the neurosciences
intensive care unit (neuro-ICU). METHODS: We conducted a prospective,
longitudinal cohort study in a single, thirty-bed neuro-ICU in a regional
comprehensive stroke and level 1 trauma center. One of two neuro-ICU services
that admit patients to the same ICU on alternating days used a palliative care
needs checklist during morning work rounds. Between March and October, 2015,
surveys were mailed to family members of patients discharged from the neuro-ICU.
RESULTS: Nearly half of surveys (n = 91, 48.1%) were returned at a median of 4.7
months. At the time of survey completion, mean Modified rankin scale score (mRS)
of neuro-ICU patients was 3.1 (SD 2). Overall ratings of quality of care were
relatively high (82.2 on a 0-100 scale) with 32% of family members meeting
screening criteria for depressive syndrome. The primary outcome measuring family
satisfaction, consisting of eight items from the Family Satisfaction in the ICU
questionnaire, did not differ significantly between families of patients from
either ICU service nor did family ratings of depression (PHQ-8) and post
traumatic stress (PCL-17). CONCLUSIONS: Among families of patients discharged
from the neuro-ICU, the daily use of a palliative care needs checklist had no
measurable effect on family satisfaction scores or long-term psychological
outcomes. Further research is needed to identify optimal interventions to meet
the palliative care needs specific to family members of patients treated in the
neuro-ICU.
PMID- 28699145
TI - Shifts in Food Preferences After Bariatric Surgery: Observational Reports and
Proposed Mechanisms.
AB - PURPOSE OF REVIEW: Bariatric surgery is currently the most effective treatment
for obesity. Roux-en-Y gastric bypass (RYGB) is the most commonly performed
bariatric procedure and results in long-term weight loss. Alterations in food
preference and choices may contribute to the long-term benefits of RYGB. This
manuscript reviews the available literature documenting changes in food
preference in both humans and experimental animals after RYGB and discusses the
current theory on the underlying mechanisms involved. RECENT FINDINGS: Obesity is
associated with an increased preference for sweet and high-fat foods, and the
most consistent evidence has been the shift away from these calorie-dense foods
in both animal and human studies after RYGB. Self-reporting is the most common
method used to record food preferences in humans, while more direct approaches
have been used in animal work. This methodological heterogeneity may give rise to
inconsistent findings. Future studies in humans should focus on direct measures
to permit corroboration of mechanistic insights gained from animal studies.
PMID- 28699146
TI - Residency Diary: Big Lessons in Small Moments.
PMID- 28699147
TI - What Are the Complications, Survival, and Outcomes After Revision to Reverse
Shoulder Arthroplasty in Patients Older Than 80 Years?
AB - BACKGROUND: By the time patients with a failed shoulder arthroplasty require
revision surgery, a substantial number are older than 80 years. The risk of
complications of revision arthroplasty in this elderly population is largely
unknown and needs to be considered when contemplating whether these patients are
too frail for revision surgery. QUESTIONS/PURPOSES: (1) What are the 90-day
medical and surgical complications after revision to reverse shoulder
arthroplasty (RSA) in patients older than 80 years? (2) What are the 2- and 5
year survival rates after revision? (3) Was there an improvement in pain at rest
or with activity, range of motion (ROM), and strength after revision surgery?
METHODS: Between 2004 and 2013, 38 patients who were older than 80 years (84 +/-
3 years) underwent revision surgery to a RSA. Of those, five were lost to
followup before 2 years, and two had died within 2 years of revision surgery,
leaving 31 for analysis of our survivorship, pain, ROM, and strength endpoints at
a minimum of 2 years or until revision surgery had occurred (mean, 28 months;
range, 1-77 months); all 38 patients were included for purposes of evaluating
medical and surgical complications at 90 days. During the period in question, our
general indication for using RSA included failure of previous shoulder
arthroplasty because of instability, glenoid loosening with bone loss, or rotator
cuff insufficiency. The indication for revision to RSA did not change during the
study period. The index procedure (revision to RSA at the age of 80 years or
older) was the first revision arthroplasty in 33 (87%) patients and the second in
five (13%) patients. We tallied 90-day medical and surgical complications by
performing a retrospective chart and institutional joint registry review. The
cumulative incidence of implant loosening (implant migration or tilting, or
complete radiolucent lines present) and revision surgery was calculated at 2 and
5 years using competing risk of death method. Pain levels at rest or with
activity (rated in a 1 to 5 Likert-type scale) were collected through a
retrospective chart review and values before and after surgery were compared.
RESULTS: Medical complications occurred in three of 38 (8%) patients and surgical
complications occurred in five of 38 (13%) patients. The 90-day mortality was 3%
(one of 38 patients), and the total mortality was 26% (10 of 38 patients). The
cumulative incidence of revision was 11% (95% CI, 0%-20%) at 2 years and 16% (95%
CI, 1%-30%) at 5 years; the cumulative incidence of loosening was 8% (95% CI, 0%
20%) at 2 years and 16% (95% CI, 1%-30%) at 5 years. Pain at rest or with
activity improved from pre- to postoperation (preoperative: median, 4 [range, 2
5]; postoperative: median, 1 [range, 1-4]; median difference: -2, 95% CI -3 to 0;
p < 0.000). The active ROM improved during the preoperative compared with
postoperative periods: mean +/- SD forward flexion of 52 degrees +/- 40 degrees
to 109 degrees +/- 44 degrees , respectively (mean difference: 56; 95% CI, 40
72; p < 0.000), and mean +/- SD external rotation of 15 degrees +/- 22 degrees
to 31 degrees +/- 21 degrees , respectively (mean difference: 16; 95% CI, 8-25;
p < 0.000). CONCLUSIONS: Age should not be used as a reason to not consider
revision surgery to RSA in patients older than 80 years. Further studies with a
prospective design, larger sample size, investigating risk factors for
complications or poor outcome, and incorporation of functional scores are
required. LEVEL OF EVIDENCE: Level IV, therapeutic study.
PMID- 28699148
TI - Editorial Comment: Improving Care for Patients with ACL Injuries: A Team
Approach.
PMID- 28699149
TI - Is the Clavicula Pro Humero Technique of Value for Reconstruction After Resection
of the Proximal Humerus in Children?
AB - BACKGROUND: There are several options for reconstruction of proximal humerus
resections after wide resection for malignant tumors in children. The clavicula
pro humero technique is a biologic option that has been used in the past, but
there are only scant case reports and small series that comment on the results of
the procedure. Because the longevity of children mandates a reconstruction with
potential longevity not likely to be achieved by other techniques, the clavicula
pro humero technique may be a potential option in selected patients.
QUESTIONS/PURPOSES: (1) How successful is the clavicula pro humero procedure in
achieving local tumor control? (2) What is the frequency of nonunion? (3) What
are the complications of the procedure? (4) What scores do patients achieve (on
the Musculoskeletal Tumor Society (MSTS) and the Toronto Extremity Salvage Score
(TESS) after this procedure? METHODS: Four university hospitals performed the
clavicula pro humero technique in eight children aged 8 to 18 years between June
2006 and February 2014. During that period, general indications for this approach
included all reconstructions of the proximal humerus for malignant tumors in
children older than 8 years. All patients were followed for a mean of 40 months
(range, 25-86 months); one patient was lost to followup before 2 years. The tumor
resections removed the rotator cuff muscles in all patients, glenohumeral joint
in five, and deltoid muscle in three. The median length of the bone defect after
resection was 20 cm (range, 7-25 cm). It was reduced to 9 cm (range, 0-17 cm) or
27% (range, 0%-64%) of the total humerus length after clavicular rotation. Direct
osteosynthesis (one patient), induced membrane technique (one patient), or
vascularized fibular autograft (six patients) was used to complete the defect
after rotation of the clavicle if necessary. Presence of union (defined as bone
healing before 10 months, as assessed by disappearance of the osteotomy on AP and
lateral view radiographs), and complications were determined by chart review
performed by a surgeon not involved in patient care. Function assessed by the
MSTS and the TESS scores were determined by the patients with their families.
RESULTS: None of the patients had tumor recurrence. One patient died of pulmonary
metastases before the 2-year followup. Proximal and distal bone unions were
achieved before 10 months without an additional surgical procedure in two and six
of seven patients, respectively. Fourteen local complications occurred resulting
in nine revision operations. The main complication was aseptic proximal
pseudarthrosis (five patients); other complications included one proximal
junction fracture, one clavicle fracture complicated by clavicle osteolysis, one
distal junction fracture, one necrosis of the skin paddle of the fibular
autograft, one glenoclavicular ossification, and one distal pseudarthrosis
complicated by a fracture of this distal junction. Function, as assessed by the
MSTS score, was a median of 23 of 30 (range, 11-27). The median TESS score was
82% (range, 75%-92%). Shoulder ROM (median; range) in abduction, front elevation,
and external and internal rotations were 70 degrees (30 degrees -90 degrees ), 75
degrees (30 degrees -85 degrees ), 10 degrees (0 degrees -20 degrees ), and 80
degrees (80 degrees -100 degrees ), respectively. Three of the seven patients
reported dissatisfaction with the cosmetic appearance. CONCLUSIONS: The clavicula
pro humero technique achieved oncologic local control after resection and
reconstruction of proximal humerus tumors in children. Although union times are
approximately 2 years and some patients underwent augmentation with other grafts,
it eventually provides a solid, painless, biologic, and stable reconstruction and
creates a mobile acromioclavicular joint and generally good function. Nonunion of
the proximal junction is the main complication of this technique. We cannot
directly compare this technique with other reconstruction options, and longer
followup is needed, but this may be a useful reconstruction option to consider in
select pediatric patients with sarcomas of the proximal humerus. LEVEL OF
EVIDENCE: Level IV, therapeutic study.
PMID- 28699150
TI - Effect of insulin infusion line on glycaemic variability in a perioperative high
dependency unit (HDU): a prospective randomised controlled trial.
AB - BACKGROUND: Glucose control is an important issue in post-operative patients. The
objective here was to compare two insulin infusion lines by syringe pumps to
assess the impact of medical devices on glycaemic variability in surgical
patients under intensive insulin therapy. This open, prospective, single-centre
randomised study was conducted in a fifteen-bed perioperative high dependency
unit (HDU) in a university hospital. In total, 172 eligible patients receiving
insulin therapy agreed to participate in the study. Subcutaneous continuous
glucose monitoring was set up for all patients and an optimised system with a
dedicated insulin infusion line for half of the patients. RESULTS: Eighty-six
patients were infused via the optimised infusion line and 86 patients via the
standard infusion line. No significant difference was found according to the
glycaemic lability index score [mean difference between groups (95% CI): -0.09 (
0.34; 0.16), p = 0.49 after multiple imputation]. A glucose control monitoring
system indicated a trend towards differences in the duration of hypoglycaemia
(blood glucose level below 70 mg dl-1 (3.9 mmol l-1) over 1000 h of insulin
infusion (9.7 +/- 25.0 h in the standard group versus 4.4 +/- 14.8 h in the
optimised group, p = 0.059) and in the number of patients experiencing at least
one hypoglycaemia incident (25.7 vs. 12.9%, p = 0.052). Time in the target range
was similar for both groups. CONCLUSIONS: The use of optimised infusion line with
a dedicated insulin infusion line did not reduce glycaemic variability but
minimised the incidence of hypoglycaemia events. The choice of the medical
devices used to infuse insulin seems important for improving the safety of
insulin infusion in perioperative HDU.
PMID- 28699151
TI - [Emotion recognition rehabilitation combined with cognitive stimulation for
people with Alzheimer's disease. Efficacy for cognition and functional aspects].
AB - INTRODUCTION: The ability to recognize facial emotional expression is essential
for social interactions and adapting to the environment. Emotion recognition is
impaired in people with Alzheimer's disease (AD), thus rehabilitation of these
skills has the potential to elicit significant benefits. AIM: To assess the
efficacy of a combined treatment of rehabilitation of emotion recognition (RER)
and cognitive stimulation (CS) for people with AD, due to its potential
implications for more effective psychosocial interventions. SUBJECTS AND METHODS:
36 patients were assigned to one of three experimental conditions: an
experimental group (EG) that received 20 sessions of RER and 20 sessions of CS; a
control group (CG) that received 40 sessions of CS, and a treatment as usual
group (TAU). RESULTS: 32 patients completed the treatment (77.53 +/- 5.43 years).
Significant differences were found in MMSE30 (F = 5.10; p = 0.013), MMSE35 (F =
4.16; p = 0.026), affect recognition (Z = -2.81; p = 0.005) and basic activities
of daily living (Z = -2.27; p = 0.018) favouring the efficacy of the combined
treatment. The TAU group showed a decline in depression (Z = -1.99; p = 0.048),
apathy (Z = -2.30; p = 0.022) and anosognosia (Z = -2.19; p = 0.028).
CONCLUSIONS: The combined treatment of RER + CS was more effective than TAU and
CS alone for the treatment of patients with AD. This is the first study about the
rehabilitation of affect recognition in AD.
PMID- 28699152
TI - [Characteristics of structural injuries in pediatric patients with focal epilepsy
in a Honduran hospital].
AB - INTRODUCTION: Epilepsy is the most commonly occurring neurological disorder in
the world. The study of structural brain lesions is important to understand the
secondary complications. In Honduras there is little information on this topic.
AIM: To determine the characteristics and proportion of structural brain lesions
in paediatric patients with focal epilepsy at the Hospital Escuela Universitario.
PATIENTS AND METHODS: A descriptive, cross-sectional, retrospective-prospective
study. The study population consisted of 162 paediatric patients with focal
epilepsy who were treated in the paediatric neurology outpatient department
between January 2015 and June 2016. On applying the eligibility and exclusion
criteria, the universe of study comprised 102 patients with focal epilepsy.
RESULTS: 41% of the patients with focal epilepsy presented a structural lesion.
The main locations of the structural lesions were the parietal lobe (12.8%), the
occipital lobe (10.8%) and the frontal lobe (10.8%). An association was found
between the presence of structural brain lesions and the presence of uncontrolled
seizures, with statistical significance. The attributable risk was calculated and
it was found that among patients with uncontrolled seizures, 67% had a structural
lesion in the imaging study. CONCLUSIONS: The presence of uncontrolled seizures
is associated to the presence of structural lesions in imaging studies, with a
high attributable risk. Leukomalacia and cerebral ischaemia were the main
findings that were reported. The predominant structural lesions in paediatric
patients with focal epilepsy in the population studied are those related to
events that take place during the peripartum period.
PMID- 28699153
TI - [Hydrocephalus due to hyperplasia of the choroid plexuses in a patient with
trisomy 9 mosaicism. A real diagnostic and therapeutic challenge].
AB - INTRODUCTION: Trisomy 9 is an unusual chromosome abnormality in live-born
patients, which is frequently accompanied by functional and structural anomalies
of the central nervous system. Among many other alterations, several studies have
been published in the English-speaking literature that show an association
between chromosome 9 abnormality and pathologies affecting the choroid plexuses.
CASE REPORT: We report the case of a 4-month-old male with trisomy 9 mosaicism
associated to hydrocephalus secondary to choroid plexus hyperplasia, who was
referred due to a clinical picture of intracranial hypertension. The
cerebrospinal fluid (CSF) drainage procedure that was initially chosen caused
massive ascites due to an excessive production of CSF, and led to a cascade of
multiple surgical interventions, which included endoscopic and drainage
procedures. CONCLUSIONS: This is another example of an association between
choroid plexus pathologies and chromosome 9 abnormality. Due to its scarce
incidence, diagnosis of hydrocephalus secondary to plexus hyperplasia is
difficult, as is selecting its most suitable treatment. In this type of
hydrocephalus there is a double pathophysiological mechanism, which involves an
increase in CSF production and a decrease in its reabsorption. Despite taking
these considerations into account, the treatment of hydrocephalus secondary to
plexus hyperplasia is a real challenge that usually leads to multiple surgical
interventions ranging from plexectomy or coagulation of the choroid plexuses to
the implantation of CSF drainage devices.
PMID- 28699154
TI - [Venezuelan consensus guidelines on the use of magnetic resonance in diagnosis
and follow up of patients with multiple sclerosis].
AB - INTRODUCTION: The clinical use of magnetic resonance (MR) in patients with
multiple sclerosis (MS) has advanced markedly over the past few years. Several
groups around the world have developed consensus guidelines about the role of MR
in MS at diagnosis and during follow up. However, in some regions is difficult to
extrapolate the recommendations. AIM: To provide recommendations for the
implementation of MR in MS patients at diagnosis and follow up in Venezuela.
DEVELOPMENT: A group of experts from Venezuela that included neurologists and
radiologists, by using the online surveys methodology as well as face to face
meetings developed the intended consensus for the use of MR during the diagnosis
and follow up of MS patients in Venezuela. Seventeen recommendations were
established based on published evidence and the expert opinion. Recommendations
focused on the role of conventional MR techniques and brain atrophy measurement
in MS patients both at diagnosis and during follow-up. CONCLUSIONS: The
recommendations of this consensus guidelines attempts to optimize the health care
and management of patients with MS in Venezuela.
PMID- 28699155
TI - [54.a Reunion Anual de la Sociedad Espanola de Neurofisiologia Clinica. Meeting
with the British Society for Clinical Neurophysiology. Communications (I)].
PMID- 28699156
TI - [Ataxia telangiectasia-like disorder -a child with a novel variant in MRE11A
gene].
PMID- 28699157
TI - Determination of cyclic volatile methylsiloxanes in personal care products by gas
chromatography.
AB - OBJECTIVE: Organosiloxanes are prevalent in personal care products (PCPs) due to
the desired properties they impart in the usage and application of such products.
However, the European Chemical Agency (ECHA) has recently published restriction
proposals on the amount of two cyclic siloxanes, octamethylcyclotetrasiloxane
(D4) and decamethylcyclotetrasiloxane (D5), allowed in wash off products such as
shampoos and conditioners which are discharged down the drain during consumer
use. This legislation will require that reliable analytical methods are available
for manufacturers and government agencies to use in documenting compliance with
the restrictions. This article proposes a simple analytical method to enable
accurate measurement of these compounds down to the circa 0.1 weight per cent
level in PCPs. METHODS: Although gas chromatography methods are reported in the
literature for quantitation of D4 and D5 in several matrices including PCPs, the
potential for generation of false positives due to contamination, co-elution and
in situ generation of cyclic volatile methylsiloxanes (cVMS) is always present
and needs to be controlled. This report demonstrates the applicability of using a
combination of emulsion break, liquid-liquid extraction and silylation sample
preparation followed by GC-FID analysis as a suitable means of analysing PCPs for
specific cVMS. RESULTS: The reliability and limitations of such methodology were
demonstrated through several round-robin studies conducted in the laboratories of
a consortium of silicone manufacturers. In addition, this report presents
examples of false positives encountered during development of the method and
presents a comparative analysis between this method and a published QuEChERS
sample preparation procedure to illustrate the potential for generation of false
positives when an inappropriate approach is applied to determination of cVMS in
personal care products. CONCLUSION: This report demonstrates that an approach to
determine cVMS levels in personal care products is to perform an emulsion break
on the sample, isolate the non-polar phase from the emulsion break and treat with
a silylation reagent to abate potential in situ formation of cyclics during the
course of GC-FID analysis. Round-robin studies conducted in laboratories
representing multiple siloxane manufacturers demonstrated the reliability of the
GC-FID method when measuring cVMS in PCPs down to circa 0.1%.
PMID- 28699158
TI - Precision Medicine in Inflammatory Bowel Diseases.
AB - Inflammatory bowel diseases (IBDs) are a lifelong condition of chronic, recurrent
inflammation in the gut. The introduction of immunomodulators and biologic agents
markedly improved the treatment of IBDs. Therefore, the use of biologics became
an essential element in the rational therapy of IBDs. Various substances are
currently evaluated in clinical trials, addressing different target structures
and offering further approaches in the field of IBD. Regarding the growing number
of treatment options, the need for prediction of therapy response became a
necessity and is the subject of the present research.
PMID- 28699159
TI - Is middle ear pressure affected by continuous positive airway pressure use?
PMID- 28699160
TI - Practical Recommendations for Therapeutic Drug Monitoring of Kinase Inhibitors in
Oncology.
AB - Despite the fact that pharmacokinetic exposure of kinase inhibitors (KIs) is
highly variable and clear relationships exist between exposure and treatment
outcomes, fixed dosing is still standard practice. This review aims to summarize
the available clinical pharmacokinetic and pharmacodynamic data into practical
guidelines for individualized dosing of KIs through therapeutic drug monitoring
(TDM). Additionally, we provide an overview of prospective TDM trials and discuss
the future steps needed for further implementation of TDM of KIs.
PMID- 28699161
TI - A postpartum perfect storm.
PMID- 28699162
TI - Spatial distribution of EGFR and KRAS mutation frequencies correlates with
histological growth patterns of lung adenocarcinomas.
AB - Multiregional analysis provided first indications for morphological and molecular
heterogeneity in lung adenocarcinomas (ADCs), but comprehensive morpho-molecular
comparisons are still lacking. The purpose of our study was to investigate the
spatial distribution of EGFR and KRAS alterations systematically throughout whole
tumor cross-sections in correlation with the tumor cell content and the
histopathological patterns. Central sections of 19 ADCs were subdivided into 467
segments of 5 mm * 5 mm. We determined the predominant histological growth
pattern and the allele frequencies of driver gene mutations by digital PCR in
every segment. We further quantified the absolute cell counts and proportions of
tumor and non-neoplastic cells in all segments to normalize the mutant allele
frequencies. Driver gene mutations could be detected in >99% of the tumor
containing segments, with high levels of inter- and intratumor heterogeneity
regarding the mutant allele frequency (range: 0.04-19.36). Different patterns for
the distribution of the variant allele frequency within a tumor were
recognizable. While some cases showed ubiquitously low or high levels, others
revealed regions with focally elevated frequencies. Differences between KRAS and
EGFR alterations were not significant. The great majority of the analyzed tumor
sections (16/19) exhibited two or more morphological growth patterns. Mutant
allele frequencies were significantly higher in segments with a predominant solid
pattern compared to all other histologies (p < 0.01). Our data indicate that
driver gene mutations are present with high levels of inter- and intratumor
heterogeneity throughout the whole tumor, with a correlation between the allele
frequencies and histological growth patterns.
PMID- 28699163
TI - Conventional sunscreen application does not lead to sufficient body coverage.
AB - OBJECTIVE: This study aimed to assess sunscreen application habits and relative
body coverage after single whole body application. METHODS: Fifty-two healthy
volunteers were asked to use the test product once, following their usual
sunscreen application routine. Standardized UV photographs, which were evaluated
by Image Analysis, were conducted before and immediately after product
application to evaluate relative body coverage. In addition to these procedures,
the volunteers completed an online self-assessment questionnaire to assess
sunscreen usage habits. RESULTS: After product application, the front side showed
significantly less non-covered skin (4.35%) than the backside (17.27%) (P =
0.0000). Females showed overall significantly less non-covered skin (8.98%) than
males (13.16%) (P = 0.0381). On the backside, females showed significantly less
non-covered skin (13.57%) (P = 0.0045) than males (21.94%), while on the front
side, this difference between females (4.14%) and males (4.53%) was not
significant. CONCLUSION: In most cases, the usual sunscreen application routine
does not provide complete body coverage even though an extra light sunscreen with
good absorption properties was used. On average, 11% of the body surface was not
covered by sunscreen at all. Therefore, appropriate consumer education is
required to improve sunscreen application and to warrant effective sun
protection.
PMID- 28699164
TI - Novel amino acid-based surfactant for silicone emulsification and its application
in hair care products: a promising alternative to quaternary ammonium cationic
surfactants.
AB - OBJECTIVE: Quaternary ammonium cationic surfactants (ACSs) and N-[3
alkyl(12,14)oxy-2-hydroxypropyl]-l-arginine hydrochloride (N-AOHPA) were used to
emulsify silicone. The potential of the resulting emulsions in hair conditioning
products was investigated. METHODS: The emulsions were prepared using a
homogenizer and/or high-pressure homogenizer. ACSs and N-AOHPA were used as
silicone emulsifiers. The stability of the emulsions was evaluated by measuring
particle sizes, creaming fractions, polydispersity indexes and zeta potentials.
Moreover, the N-AOHPA-stabilized emulsion was compared with the ACS-stabilized
emulsion to evaluate the adsorption amount of silicone on healthy and bleached
hair surfaces and the inhibitory effects on amino acid dissolution from bleached
hair. The adsorption site of the N-AOHPA-stabilized emulsion was observed using a
scanning electron microscope. RESULTS: For all surfactants, the silicone
emulsions prepared using the high-pressure homogenizer were more stable than
those prepared using the homogenizer. When N-AOHPA was used as the surfactant,
the silicone emulsion was especially stable. Furthermore, the d50 value of the N
AOHPA-stabilized emulsion was smaller than that of the ACS-stabilized emulsion.
The adsorption behaviour of the silicone droplets in the different emulsions
varied depending on the nature of the surfactant and the preparation method. The
amount of ACS-stabilized silicone adsorbed on healthy hair was higher than that
adsorbed on bleached hair, especially when the emulsion was prepared using the
homogenizer. In contrast, the amount of N-AOHPA-stabilized silicone adsorbed on
bleached hair was high, and no differences were observed between the N-AOHPA
stabilized emulsions prepared using the homogenizer and high-pressure
homogenizer. The emulsified droplets, especially the N-AOHPA-stabilized droplets
prepared using the high-pressure homogenizer, prevented amino acid dissolution
from bleached hair. It was concluded that the silicone droplet adsorption site
affected the dissolution process because the small N-AOHPA-stabilized droplets
adsorbed at cuticle edges. CONCLUSION: This study shows that N-AOHPA has good
potential for use as an emulsifier in products used for improving the condition
of damaged hair.
PMID- 28699165
TI - Ultrasound-guided core needle biopsy in salivary glands: A meta-analysis.
AB - OBJECTIVES/HYPOTHESIS: Core needle biopsy is an effective diagnostic tool widely
used in many oncological diagnostic approaches. It provides an adequate tissue
sample for histological evaluation of architecture, which allows tumor grading
and classification of malignant and benign tumors. This study aimed to provide an
updated meta-analysis and systematic review of core needle biopsy in the salivary
glands. STUDY DESIGN: A literature search using PubMed, Embase, and the Cochrane
Library through December 2016. METHODS: Data on true positives, true negatives,
false positives, and false negatives were extracted from the relevant articles.
Methodological quality was assessed using the Quality Assessment of Diagnostic
Accuracy Studies 2 tool. We calculated accuracy, sensitivity, and specificity
with 95% confidence intervals (CIs) using random-effects models that considered
both within- and between-study variations. RESULTS: Our search included 10
observational studies. For core needle biopsy, the sensitivity and specificity
for the diagnosis of salivary glands were 0.94 (95% CI: 0.92-0.96, I2 = 18.7%,
chi2 P = .27) and 0.98 (95% CI: 0.97-0.99, I2 = 79.6%, chi2 P = .00),
respectively. The area under the summary receiver operating characteristic curve
was 0.98 (95% CI: 0.97-0.99). Seven hematomas, one case of temporary facial
paralysis caused by local anesthesia, and no tumor seeding were reported from a
total of 1,315 procedures. CONCLUSIONS: Ultrasound core needle biopsy of salivary
glands is an excellent diagnostic tool in terms of accuracy, technical
performance, and safety profile. LEVEL OF EVIDENCE: NA. Laryngoscope, 128:118
125, 2018.
PMID- 28699166
TI - Not bitten by the bug: A CD30+ lymphoproliferative disorder masquerading as
arthropod bites.
PMID- 28699167
TI - Raising Standards for the Evaluation of Future Psoriasis Therapeutics: A Critical
Checklist.
AB - The quality of life for a patient has been transformed in the last 15 years due
to innovations that have resulted in better treatments for severe psoriasis, a
chronic inflammatory cutaneous disease. Now, novel therapies for psoriasis need
to reach a high standard in order to offer patients with psoriasis a genuine
alternative. Here we outline a suggested critical checklist that will help
industry sponsors, researchers, and clinicians evaluate novel therapeutics for
psoriasis.
PMID- 28699168
TI - Intellectual disability in children aged less than seven years born moderately
and late preterm compared with very preterm and term-born children - a nationwide
birth cohort study.
AB - BACKGROUND: Prematurity has been shown to be associated with an increased risk of
intellectual disability (ID). METHOD: The aim was to establish whether the
prevalence of ID, defined as significant limitations in both intellectual
(intelligence quotient below 70) and adaptive functioning among moderately
preterm (MP; 32+0 -33+6 weeks) and late preterm (LP; 34+0 -36+6 weeks) infants,
is increased compared with that in term infants (>=37+0 weeks). Antenatal and
neonatal risk factors for ID among gestational age groups were sought. The
national register study included all live-born infants in Finland in 1991-2008,
excluding those who died before one year age, or had any major congenital anomaly
or missing data. A total of 1 018 256 infants (98.0%) were analysed: very preterm
(VP; <32+0 weeks, n = 6329), MP (n = 6796), LP (n = 39 928) and term (n = 965
203). RESULTS: By the age of seven years, the prevalence of ID was 2.48% in the
VP group, 0.81% in the MP group, 0.55% in the LP group and 0.35% in the term
group. Intracranial haemorrhage increased the ID risk in all groups. Male sex and
born small for gestational age predicted an increased risk in all but the MP
group. CONCLUSIONS: The prevalence of ID decreased with increasing gestational
age. Prevention of intracranial haemorrhages may have a beneficial effect on the
neurodevelopmental outcomes of neonates.
PMID- 28699169
TI - Validity and reliability of the oral health-related caregiver burden index.
AB - OBJECTIVE: This study developed the Oral Health-related Caregiver Burden Index
(OHBI), which contains nine questions with five response options each. As a
secondary objective, we aimed to clarify the relationship between oral health
related caregiver burden and general caregiver burden. BACKGROUND: There are a
few reports of the oral health-related caregiver burden. METHODS: Between January
2016 and February 2016, 155 participants enrolled in the study. We conducted the
survey to examine the validity and reliability of OHBI. Additionally, the cut-off
score for this scale was calculated, and the relationship between OHBI and
general caregiver burden (BIC-11) was examined by binomial logistic regression.
RESULTS: Survey 1 was completed by 102 caregivers, of whom 58 (56.9%) were
female. Survey 2 was completed by 40 caregivers, of whom 22 (55.0%) were female.
Factor analysis revealed four factors in OHBI. Cronbach's alpha was .691-.866.
OHBI scores were significantly associated with scores for each factor of the BIC
11. OHBI had a cut-off score of 10 (AUC=.881, sensitivity=.828,
specificity=.744). A good-poor analysis revealed significant differences for
discriminant validity. ICC, an indicator of reliability, was .449-.842. There was
a significant relationship between caregiver burden and oral health-related
caregiver burden according to binomial logistic regression analysis (P<.05).
CONCLUSION: We developed the OHBI as a multidimensional care burden scale, which
comprises nine items covering five domains. Further, we verified the relationship
between general caregiver burden and oral health-related caregiver burden.
PMID- 28699170
TI - Marked leukemoid reaction in a patient with metastatic breast carcinoma.
PMID- 28699171
TI - Alpha-1-antitrypsin for the treatment of steroid-refractory acute
gastrointestinal graft-versus-host disease.
PMID- 28699172
TI - Outcomes of medialization laryngoplasty with and without arytenoid adduction.
AB - OBJECTIVES/HYPOTHESIS: To evaluate the effect of medialization laryngoplasty (ML)
performed alone compared to ML with arytenoid adduction (AA) on glottic gap and
voice quality in unilateral vocal fold paralysis (UVFP) patients. STUDY DESIGN:
Retrospective case series. METHODS: UVFP patients treated with ML alone and ML
with AA at the University of California San Francisco Voice and Swallowing Center
were identified. Demographic information and history of laryngeal procedures were
collected. Preoperative and postoperative examinations were digitally analyzed
using ImageJ for normalized anterior and posterior glottic gap and voice samples
graded with CAPE-V scores. RESULTS: Forty-seven patients underwent ML and 27
patients underwent ML with AA. Normalized anterior gap (AG) improved in both ML
(preop: 4.4 pixel units (u), postop: 0.8 u; P < 0.001) and ML with AA groups
(preop: 3.3 u, postop 0.6 u; P < 0.001). There was no statistically significant
difference in normalized AG values between treatment groups. Postoperative
normalized posterior gap (PG) improved in the ML with AA group only (preop: 1.8
u, postop: 0.5 u; P = 0.01). Overall severity, roughness, and strain voice
parameters had acceptable reliability for analysis. Overall severity improved in
ML (preop: 54, postop: 27; P < 0.001) and ML with AA (preop: 44, postop: 24; P =
0.005). There was no statistically significant difference in any voice parameter
between treatment groups. CONCLUSION: UVFP patients undergoing ML may benefit
from addition of AA when a large posterior glottic gap is present. In this study,
ML with AA but not ML alone resulted in statistically significant improvement in
PG. LEVEL OF EVIDENCE: 4. Laryngoscope, 127:2591-2595, 2017.
PMID- 28699173
TI - Porous Silicon Nanoparticle Delivery of Tandem Peptide Anti-Infectives for the
Treatment of Pseudomonas aeruginosa Lung Infections.
AB - There is an urgent need for new materials to treat bacterial infections. In order
to improve antibacterial delivery, an anti-infective nanomaterial is developed
that utilizes two strategies for localization: i) a biodegradable nanoparticle
carrier to localize therapeutics within the tissue, and ii) a novel tandem
peptide cargo to localize payload to bacterial membranes. First, a library of
antibacterial peptides is screened that combines a membrane-localizing peptide
with a toxic peptide cargo and discovers a tandem peptide that displays synergy
between the two domains and is able to kill Pseudomonas aeruginosa at sub
micromolar concentrations. To apply this material to the lung, the tandem peptide
is loaded into porous silicon nanoparticles (pSiNPs). Charged peptide payloads
are loaded into the pores of the pSiNP at ~30% mass loading and ~90% loading
efficiency using phosphonate surface chemistry. When delivered to the lungs of
mice, this anti-infective nanomaterial exhibits improved safety profiles over
free peptides. Moreover, treatment of a lung infection of P. aeruginosa results
in a large reduction in bacterial numbers and markedly improves survival compared
to untreated mice. Collectively, this study presents the selection of a
bifunctional peptide-based anti-infective agent and its delivery via
biodegradable nanoparticles for application to an animal model of lung infection.
PMID- 28699175
TI - Long-term health outcomes of adults with McCune-Albright syndrome.
AB - CONTEXT: McCune-Albright syndrome (MAS) is associated with numerous health
problems. Comprehensive long-term health problems of adults with MAS are less
well defined in the literature. OBJECTIVE: Our objective is to report
comprehensive health outcomes of adults with MAS (>18 years). DESIGN:
Retrospective case note review of 16 adults with MAS managed by one clinician.
Results expressed as median (range). RESULTS: The study included 16 adults (seven
males) with MAS. Median current age is 29 years (20, 46). Twelve of 16 had
craniofacial fibrous dysplasia with five of 12 (42%) with progressive facial
asymmetry. Growth hormone excess was observed in six of 16 (38%) and T3-toxicosis
in five of 16 (31.3%). Six of the seven men (86%) had abnormalities on testicular
ultrasound with one man exhibiting marked atrophy of germ and sertoli cells with
reduction in spermatogenesis. Six of the 16 (38%) had cardiorespiratory
complications including high output cardiac failure (n,3), hypertension (n,2) and
one man with congestive cardiac failure and restrictive lung disease. Six of
eight (66%) who had screening endoscopy for upper gastrointestinal polyps show
increasing numbers of polyps, with benign histology to date. One woman with a
previous history of early puberty presented with early aggressive breast
carcinoma, which was positive for GNAS. Two patients had GNAS-positive muscle
myomas. Platelet dysfunction with bleeding tendency responsive to platelet
transfusion during surgery was seen in four. CONCLUSION: A range of complex
health problems is encountered in adults with MAS. These have important
implications for transition of patients with MAS and adult care. Long-term cancer
risk is currently unknown but requires careful follow-up.
PMID- 28699176
TI - A descriptive qualitative study of perceptions of parents on their child's
vaccination.
AB - AIMS AND OBJECTIVES: To explore the perceptions of parents on their child's
vaccination in Singapore. BACKGROUND: Vaccination is a key part of health care,
and the management of vaccination for children has gained increasing interest
globally. Previous studies found that parents had multiple concerns and low
confidence in making vaccination decisions for their children. As no study in
this area has been conducted in Singapore, the views and needs of parents
regarding their child's vaccination remain unknown. DESIGN: Descriptive
qualitative study. METHODS: Purposive sampling was used to recruit 19 parents of
children undergoing routine vaccination in a clinic in Singapore. Semistructured
face-to-face or telephone interviews were conducted using an interview guide and
were audiorecorded. Thematic analysis was used to analyse the data. RESULTS: The
thematic analysis generated four themes from 15 subthemes. Theme 1 summarised the
factors promoting vaccination uptake, theme 2 was factors impeding vaccination
compliance, theme 3 described parents' supportive roles before, during and after
the vaccination, and theme 4 was about parents' need for improvement in
vaccination services, information and communication with healthcare
professionals. CONCLUSIONS: This study provided insight into parental views,
experiences and needs regarding their child's vaccination. The results suggest a
need for developing intervention programmes addressing information needs and pain
management strategies to improve parents' experiences regarding their children's
vaccination. RELEVANCE TO CLINICAL PRACTICE: Healthcare professionals and
policymakers should take actions to improve parents' experiences regarding their
child's vaccination by minimising the impeding factors and improving services,
information provided and communications with parents.
PMID- 28699174
TI - Inherited variation in circadian rhythm genes and risks of prostate cancer and
three other cancer sites in combined cancer consortia.
AB - Circadian disruption has been linked to carcinogenesis in animal models, but the
evidence in humans is inconclusive. Genetic variation in circadian rhythm genes
provides a tool to investigate such associations. We examined associations of
genetic variation in nine core circadian rhythm genes and six melatonin pathway
genes with risk of colorectal, lung, ovarian and prostate cancers using data from
the Genetic Associations and Mechanisms in Oncology (GAME-ON) network. The major
results for prostate cancer were replicated in the Prostate, Lung, Colorectal and
Ovarian (PLCO) cancer screening trial, and for colorectal cancer in the Genetics
and Epidemiology of Colorectal Cancer Consortium (GECCO). The total number of
cancer cases and controls was 15,838/18,159 for colorectal, 14,818/14,227 for
prostate, 12,537/17,285 for lung and 4,369/9,123 for ovary. For each cancer site,
we conducted gene-based and pathway-based analyses by applying the summary-based
Adaptive Rank Truncated Product method (sARTP) on the summary association
statistics for each SNP within the candidate gene regions. Aggregate genetic
variation in circadian rhythm and melatonin pathways were significantly
associated with the risk of prostate cancer in data combining GAME-ON and PLCO,
after Bonferroni correction (ppathway < 0.00625). The two most significant genes
were NPAS2 (pgene = 0.0062) and AANAT (pgene = 0.00078); the latter being
significant after Bonferroni correction. For colorectal cancer, we observed a
suggestive association with the circadian rhythm pathway in GAME-ON (ppathway =
0.021); this association was not confirmed in GECCO (ppathway = 0.76) or the
combined data (ppathway = 0.17). No significant association was observed for
ovarian and lung cancer. These findings support a potential role for circadian
rhythm and melatonin pathways in prostate carcinogenesis. Further functional
studies are needed to better understand the underlying biologic mechanisms.
PMID- 28699177
TI - Association between age-related reductions in testosterone and risk of prostate
cancer-An analysis of patients' data with prostatic diseases.
AB - The relationship between serum total testosterone and prostate cancer (PCa) risk
is controversial. The hypothesis that faster age-related reduction in
testosterone is linked with increased PCa risk remains untested. We conducted our
study at a tertiary-level hospital in southeast of the USA, and derived data from
the Medical Registry Database of individuals that were diagnosed of any prostate
related disease from 2001 to 2015. Cases were those diagnosed of PCa and had one
or more measurements of testosterone prior to PCa diagnosis. Controls were those
without PCa and had one or more testosterone measurements. Multivariable logistic
regression models for PCa risk of absolute levels (one-time measure and 5-year
average) and annual change in testosterone were respectively constructed. Among a
total of 1,559 patients, 217 were PCa cases, and neither one-time measure nor 5
year average of testosterone was found to be significantly associated with PCa
risk. Among the 379 patients with two or more testosterone measurements, 27 were
PCa cases. For every 10 ng/dL increment in annual reduction of testosterone, the
risk of PCa would increase by 14% [adjusted odds ratio, 1.14; 95% confidence
interval (CI), 1.03-1.25]. Compared to patients with a relatively stable
testosterone, patients with an annual testosterone reduction of more than 30
ng/dL had 5.03 [95% CI: 1.53, 16.55] fold increase in PCa risk. This implies a
faster age-related reduction in, but not absolute level of serum total
testosterone as a risk factor for PCa. Further longitudinal studies are needed to
confirm this finding.
PMID- 28699178
TI - Task-based changes in proton MR spectroscopy signal during configural working
memory in human medial temporal lobe.
AB - PURPOSE: To detect local cholinergic changes in human medial temporal lobe during
configural working memory performance. MATERIALS AND METHODS: Proton magnetic
resonance spectroscopy (1 H-MRS) measurements were acquired at 3T from a 2 * 2 *
3 cm voxel in right medial temporal lobe from 36 subjects during performance of a
configural visual working memory task (cWMT). In order to compensate for expected
task-based blood oxygenation level-dependent (BOLD) T2 * effects, resonance
signal changes of unbound choline-containing metabolites (Cho) were referenced to
an internal standard of creatine + phosphocreatine metabolites (Cre) and compared
between four task blocks: rest, memorization, active memory maintenance, and
recognition. An unannounced memory retention test was conducted in 21 subjects.
Quality assurance analyses examined task-based Cho and Cre individually as well
as referenced to resonance signal from N-acetylaspartate (NAA). RESULTS:
Increases from a resting baseline in the Cho/Cre ratio were observed during 60
second blocks of active memory maintenance across the group (P = 0.0042).
Behavioral accuracy during task performance correlated with memory retention (r =
0.48, P = 0.027). Quality assurance measures showed task-based changes in Cre
resonance signal both individually (P = 0.00099) and when utilized as a
noncholinergic internal reference (NAA/Cre, P = 0.00079). CONCLUSION: Increases
in human medial temporal lobe 1 H-MRS Cho/Cre ratio occur during the maintenance
of configural working memory information. However, interpretation of these
results as driven by cholinergic activity cannot be assumed, as NAA, a
noncholinergic metabolite, shows similar results when utilizing Cre as a
reference. Caution is advised when considering Cre as an internal standard for
task-based 1 H-MRS measurements. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 1
J. Magn. Reson. Imaging 2018;47:682-691.
PMID- 28699179
TI - Colorectal Cancer Stem Cells Acquire Chemoresistance Through the Upregulation of
F-Box/WD Repeat-Containing Protein 7 and the Consequent Degradation of c-Myc.
AB - The cancer stem cell (CSC) paradigm suggests that tumors are organized
hierarchically. Chugai previously established an LGR5+ human colorectal cancer
(CRC) stem-cell-enriched cell line (colorectal CSCs) that expresses well-accepted
colorectal CSC markers and that can dynamically switch between proliferative and
drug-resistant noncycling states. We performed this study to elucidate the
molecular mechanisms responsible for evading cell death in colorectal CSCs
mediated by anticancer agents. During the cell cycle arrest caused by anticancer
agents, we found that c-Myc expression was substantially decreased in colorectal
CSCs. The c-Myc expression alterations were mediated by upregulation of F-box/WD
repeat-containing protein 7 (FBXW7), as evidenced through FBXW7-small interfering
RNA knockdown experiments that resulted in enhanced cell sensitivity to
anticancer agents. Upregulation of FBXW7 following drug treatment was not evident
in commercially available cancer cell lines. Colorectal CSCs were induced to
differentiation by Matrigel and fetal bovine serum. Differentiated CSCs treated
with anticancer agents did not show upregulation of FBXW7 and were more sensitive
to irinotecan (CPT-11), highlighting the potential CSC-specific nature of our
data. The FBXW7 over-expression was further validated in resected liver
metastatic sites in CRC patients after chemotherapy. In conclusion, our study
revealed that a CSC-specific FBXW7-regulatory mechanism is strongly associated
with resistance to chemotherapeutic agents. Inhibition of FBXW7-upregulation in
CSCs following chemotherapy may enhance the response to anticancer agents and
represents an attractive strategy for the elimination of colorectal CSCs. Stem
Cells 2017;35:2027-2036.
PMID- 28699180
TI - A tribute to D'Arcy Wentworth Thompson: Elucidation of a developmental principle.
AB - We show the vertebrate anterior -posterior axis is made by time space translation
(TST). 1/ TST of Hox temporal to spatial collinearity makes the trunk part of the
axis. 2/TST continues into the head. 3/ TST is mediated by collinear Hox-Hox
interactions. 4/ 'Decision points' involving signalling pathways separate axial
domains.
PMID- 28699181
TI - Predicting in a predicament: Stroke and hemorrhage risk prediction in dialysis
patients with atrial fibrillation.
AB - Whether to anticoagulate dialysis patients with atrial fibrillation is a common
clinical dilemma with limited high-quality data to inform decision-making. While
the efficacy and safety of anticoagulation for stroke prevention in dialysis
patients with atrial fibrillation has long been debated and remains unclear, the
more upstream issue of stroke risk assessment from atrial fibrillation has
received relatively little attention. In the general population, a handful of
risk scores to help predict stroke and hemorrhage risk in the setting of atrial
fibrillation are widely validated and applied in clinical practice. But are they
applicable to the dialysis population? The most commonly used stroke risk scores,
CHADS2 and CHA2DS2-VASC, have limited validation in the dialysis population, and
when validated, have shown poor performance (c-statistics <0.70). Stroke risk
scores derived in the general atrial fibrillation population may perform poorly
in dialysis patients for a number of reasons. Dialysis patients have unique
stroke risk factors, such as chronic inflammation and vascular calcification, and
a much higher competing risk of death, none of which are accounted for in current
risk scores. Further complicating the dilemma of anticoagulation is hemorrhage
risk, which is known to be exceedingly high in dialysis patients. Currently
available hemorrhage risk scores, such as HAS-BLED, have not been validated in
dialysis patients and will likely underestimate hemorrhage risk. Moving forward,
risk tools specific to the dialysis population are needed to accurately assess
and balance stroke and hemorrhage risks in dialysis patients with atrial
fibrillation.
PMID- 28699182
TI - Amygdala and hippocampus volumes are differently affected by childhood trauma in
patients with bipolar disorders and healthy controls.
AB - OBJECTIVES: Volumetric studies on deep gray matter structures in bipolar disorder
(BP) have reported contrasting results. Childhood trauma, a relevant
environmental stressor for BP, could account for the variability of the results,
modulating differences in the amygdala and hippocampus in patients with BP
compared with healthy controls (HC). Our study aimed to test this hypothesis.
METHODS: We assessed 105 outpatients, diagnosed with bipolar disorder type I (BP
I) or bipolar disorder type II (BP-II) according to DSM-IV-TR criteria, and 113
HC subjects. History of childhood trauma was obtained using the Childhood Trauma
Questionnaire (CTQ). High-resolution magnetic resonance imaging was performed on
all subjects and volumes of the amygdala, hippocampus, nucleus accumbens,
caudate, pallidum, putamen, and thalamus were measured using FreeSurfer. RESULTS:
Patients with BP showed a global reduction of deep gray matter volumes compared
to HCs. However, childhood trauma modulated the impact of the diagnosis
specifically on the amygdala and hippocampus. Childhood trauma was associated
with bilateral decreased volumes in HCs and increased volumes in patients with
BP. CONCLUSIONS: The results suggest that childhood trauma may have a different
effect in health and disease on volumes of gray matter in the amygdala and
hippocampus, which are brain areas specifically involved in response to stress
and emotion processing.
PMID- 28699183
TI - How bacterial cell division might cheat turgor pressure - a unified mechanism of
septal division in Gram-positive and Gram-negative bacteria.
AB - An important question for bacterial cell division is how the invaginating septum
can overcome the turgor force generated by the high osmolarity of the cytoplasm.
I suggest that it may not need to. Several studies in Gram-negative bacteria have
shown that the periplasm is isoosmolar with the cytoplasm. Indirect evidence
suggests that this is also true for Gram-positive bacteria. In this case the
invagination of the septum takes place within the uniformly high osmotic pressure
environment, and does not have to fight turgor pressure. A related question is
how the V-shaped constriction of Gram-negative bacteria relates to the plate-like
septum of Gram-positive bacteria. I collected evidence that Gram-negative
bacteria have a latent capability of forming plate-like septa, and present a
model in which septal division is the basic mechanism in both Gram-positive and
Gram-negative bacteria.
PMID- 28699184
TI - Control of Ice Propagation by Using Polyelectrolyte Multilayer Coatings.
AB - Ice propagation is of great importance to the accumulation of ice/frost on solid
surfaces. However, no investigation has been reported on the tuning of ice
propagation through a simple coating process. Herein, we study the ice
propagation behavior on polyelectrolyte multilayer (PEM) surfaces coated with the
layer-by-layer (LBL) deposition approach. We discover that ice propagation is
strongly dependent on the amount of water in the outermost layer of PEMs, that
is, the ice propagation rate increases with the amount of water in the outermost
layer. The ice propagation rate can be tuned by up to three orders of magnitude
by changing the polyelectrolyte pairs, counterions of the outermost polymer
layer, or the salt concentration during the preparation of PEMs. Because the
simple, versatile, and inexpensive LBL deposition approach is generally
applicable to almost all available surfaces, the PEM coatings can tune ice
propagation on a wide range of substrates.
PMID- 28699185
TI - Chromosome 6q deletion correlates with poor prognosis and low relative expression
of FOXO3 in chronic lymphocytic leukemia patients.
PMID- 28699186
TI - Cancer-Related Systemic Inflammation: The Challenges and Therapeutic
Opportunities for Personalized Medicine.
AB - Over the last decade there has been significant progress towards the development
of personalized or "precision" medicine for many patients with cancer. However,
there still remain subpopulations of cancer patients that do not possess a tumor
mutation profile that is successfully targeted by the newer molecular anticancer
drugs and further personalized approaches are needed. The presence of cancer
related systemic inflammation represents an underappreciated subpopulation of
cancer patients needing personalized therapy. For ~25% of all advanced cancer
patients, regardless of histological subtype, the patients with systemic
inflammation have significantly poorer response to chemotherapy and also shorter
overall survival compared to those cancer patients without inflammation. The
development of cancer-related systemic inflammation involves interactions between
host and tumor cells that are potential new drug targets in cancer chemotherapy.
In this review we discuss the challenges and clinical opportunities to develop
new therapeutic strategies for this underappreciated drug target.
PMID- 28699187
TI - Does transcranial electrical stimulation enhance corticospinal excitability of
the motor cortex in healthy individuals? A systematic review and meta-analysis.
AB - Numerous studies have explored the effects of transcranial electrical stimulation
(tES) - including anodal transcranial direct current stimulation (a-tDCS),
cathodal transcranial direct current stimulation (c-tDCS), transcranial
alternative current stimulation (tACS), transcranial random noise stimulation
(tRNS) and transcranial pulsed current stimulation (tPCS) - on corticospinal
excitability (CSE) in healthy populations. However, the efficacy of these
techniques and their optimal parameters for producing robust results has not been
studied. Thus, the aim of this systematic review was to consolidate current
knowledge about the effects of various parameters of a-tDCS, c-tDCS, tACS, tRNS
and tPCS on the CSE of the primary motor cortex (M1) in healthy people. Leading
electronic databases were searched for relevant studies published between January
1990 and February 2017; 126 articles were identified, and their results were
extracted and analysed using RevMan software. The meta-analysis showed that a
tDCS application on the dominant side significantly increases CSE (P < 0.01) and
that the efficacy of a-tDCS is dependent on current density and duration of
application. Similar results were obtained for stimulation of M1 on the non
dominant side (P = 0.003). The effects of a-tDCS reduce significantly after 24 h
(P = 0.006). Meta-analysis also revealed significant reduction in CSE following c
tDCS (P < 0.001) and significant increases after tRNS (P = 0.03) and tPCS (P =
0.01). However, tACS effects on CSE were only significant when the stimulation
frequency was >=140 Hz. This review provides evidence that tES has substantial
effects on CSE in healthy individuals for a range of stimulus parameters.
PMID- 28699188
TI - Culprit plaque characteristics in younger versus older patients with acute
coronary syndromes: An optical coherence tomography study from the FORMIDABLE
registry.
AB - OBJECTIVES: Culprit plaque characteristics in young patients who experience an
Acute Coronary Syndrome (ACS) evaluated by OCT (Optical Coherence Tomography)
have to be defined. The OCT-FORMIDABLE is a multicentre retrospective registry
enrolling consecutive patients with ACS who performed OCT in 9 European centres.
METHODS: Patients were divided in two groups according to age at presentation:
juvenile-ACS (age <= 50 years) and not juvenile-ACS (age > 50 years). Primary end
point was the prevalence of plaque rupture (PR). Secondary end point was the
prevalence of thin cap fibro atheroma (TCFA), fibrocalcific and fibrotic plaque.
RESULTS: 285 patients were included, 71 (24.9%) in juvenile-ACS group and 215
(75.1%) in not juvenile-ACS group. Younger patients showed a trend for a higher
prevalence of TCFA (70 vs. 58%, P = 0.06) and thrombus presence (62 vs. 51%, P =
0.1), while no statistical difference concerning PR (70 vs. 64%, P = 0.29). Of
interest patients younger that 35 years showed a higher prevalence of PR compared
to patients aged between 35 and 45 or 45 and 50 years (100 vs. 72 vs. 55%, P =
0.03). Culprit plaque in juvenile-ACS group showed more frequently a reduced mean
cap thickness (119 +/- 66 vs. 155 +/- 95 nm, P = 0.05) and less frequently
fibrotic (32 vs. 57%, P < 0.001) or fibrocalcific (17 vs. 36%, P = 0.003)
characteristics. CONCLUSION: young patients with ACS show a trend for a higher
prevalence of culprit PR, a thinner cap and less fibrotic or fibrocalcific
components.
PMID- 28699189
TI - Human papillomavirus infects placental trophoblast and Hofbauer cells, but
appears not to play a causal role in miscarriage and preterm labor.
AB - INTRODUCTION: Recently, an association between human papillomavirus infection and
both spontaneous abortion and spontaneous preterm delivery was suggested.
However, the reported human papillomavirus prevalence in pregnant women varies
considerably and reliable conclusions are difficult. We aimed to investigate
human papillomavirus infection in placental tissue of a Danish study cohort.
Furthermore, we studied the cellular localization of human papillomavirus.
MATERIAL AND METHODS: In this prospective case-control study, placental tissue
was analyzed for human papillomavirus infection by nested PCR in the following
four study groups: full-term delivery (n = 103), spontaneous preterm delivery (n
= 69), elective abortion (n = 54), and spontaneous abortion (n = 44). Moreover,
human papillomavirus cellular target was identified using in situ hybridization.
RESULTS: Human papillomavirus prevalence in placental tissue was 8.7% in full
term deliveries, 8.8% in spontaneous preterm deliveries, 10.9% in spontaneous
abortions, and 20.4% in elective abortions. Twelve different human papillomavirus
types were detected, and placental human papillomavirus infection was associated
to a disease history of cervical cancer. Human papillomavirus DNA was identified
in trophoblast cells, cells of the placental villi mesenchyme including Hofbauer
cells, and in parts of the encasing endometrium. CONCLUSION: Placental human
papillomavirus infections are not likely to constitute a risk factor for
spontaneous preterm labor or spontaneous abortions in the Danish population,
although an effect of human papillomavirus DNA in placental cells cannot be
excluded.
PMID- 28699190
TI - Poly(ethylene glycol)s as Ligands in Calcium-Catalyzed Cyclic Carbonate
Synthesis.
AB - Herein the use of CaI2 in combination with poly(ethylene glycol) dimethyl ether
(PEG DME 500) as an efficient catalyst system for the addition of CO2 to epoxides
is reported. This protocol is based on a nontoxic and abundant metal in
conjunction with a polymeric ligand. Fifteen terminal epoxides were converted at
room temperature to give the desired products in yields up to 99 %. Notably, this
system was also effective for the synthesis of twelve challenging internal
carbonates in yields up to 98 %.
PMID- 28699191
TI - A reappraisal of the benefit-risk profile of hydroxyurea in polycythemia vera: A
propensity-matched study.
AB - The use of hydroxyurea (HU) as first line therapy in polycythemia vera (PV) has
been criticized because no solid demonstration that this drug prevents thrombosis
or prolongs survival has been so far produced. Here we present the outcomes of a
large cohort of patients with PV included in the European Collaborative Low-dose
Aspirin (ECLAP) study. We selected 1,042 patients who, during the follow-up, had
received only phlebotomy (PHL) or HU to maintain the hematocrit level < 45%. To
assure comparability, we conducted a propensity score matching analysis. The two
groups (PHL n = 342 and HU n = 681) were well balanced for the parameters
included in the propensity score (overall balance: chi2 = 2.44, P = 0.964). Over
a comparable period of follow-up (PHL = 29.9 vs. HU = 34.7 months), we documented
an advantage of HU over PHL consistently significant with respect to the
incidence of fatal/non-fatal cardiovascular (CV) events (5.8 vs. 3.0 per 100
person-years in PHL vs. HU group, P = 0.002) and myelofibrosis transformation
that was only experienced by patients of PHL group. Evolution to acute leukemia
was registered in three patients (two in PHL and one in HU group). The excess of
mortality and total CV events in the PHL patients was restricted to the high-risk
group, and, compared with HU cases, was significant higher in the PHL patients
who failed to reach the hematocrit target < 0.45% (P = 0.000). In conclusion,
this analysis provides reliable and qualified estimates of the therapeutic
profile of HU and PHL treatments for future experimental studies and for the
management of PV in clinical practice.
PMID- 28699192
TI - What is the potential clinical utility of vHIT when assessing adult patients with
dizziness?
PMID- 28699193
TI - Outcomes of laryngohyoid suspension techniques in an ovine model of profound
oropharyngeal dysphagia.
AB - OBJECTIVES/HYPOTHESIS: To evaluate the efficacy of various techniques of
laryngohyoid suspension in the elimination of aspiration utilizing a cadaveric
ovine model of profound oropharyngeal dysphagia. STUDY DESIGN: Animal study.
METHODS: The head and neck of a Dorper cross ewe was placed in the lateral
fluoroscopic view. Five conditions were tested: baseline, thyroid cartilage to
hyoid approximation (THA), thyroid cartilage to hyoid to mandible (laryngohyoid)
suspension (LHS), LHS with cricopharyngeus muscle myotomy (LHS-CPM), and
cricopharyngeus muscle myotomy (CPM) alone. Five 20-mL trials of barium sulfate
were delivered into the oropharynx under fluoroscopy for each condition. Outcome
measures included the penetration aspiration scale (PAS) and the National
Institutes of Health (NIH) Swallow Safety Scale (NIH-SSS). RESULTS: Median
baseline PAS and NIH-SSS scores were 8 and 6, respectively, indicating severe
impairment. THA scores were not improved from baseline. LHS alone reduced the PAS
to 1 (P = .025) and NIH-SSS to 2 (P = .025) from baseline. LHS-CPM reduced the
PAS to 1 (P = .025) and NIH-SSS to 0 (P = .025) from baseline. CPM alone did not
improve scores. LHS-CPM displayed improved NIH-SSS over LHS alone (P = .003).
CONCLUSIONS: This cadaveric model represents end-stage profound oropharyngeal
dysphagia such as what could result from severe neurological insult. CPM alone
failed to improve fluoroscopic outcomes in this model. Thyrohyoid approximation
also failed to improve outcomes. LHS significantly improved both PAS and NIH-SSS.
The addition of CPM to LHS resulted in improvement over suspension alone. LEVEL
OF EVIDENCE: NA. Laryngoscope, 127:E422-E427, 2017.
PMID- 28699194
TI - Inverted schneiderian papilloma of the supraglottis: Case report.
AB - Inverted schneiderian papillomas are rare benign tumors, most often arising from
the sinonasal mucosa. We describe a case of a 59-year-old female with an inverted
papilloma of the supraglottis. This is the first reported case of a supraglottic
presenting inverted papilloma. Although rare, this case demonstrates that these
tumors should be considered during workup of supraglottic laryngeal masses.
Laryngoscope, 127:2830-2832, 2017.
PMID- 28699195
TI - Model-based Meta-Analysis on the Efficacy of Pharmacological Treatments for
Idiopathic Pulmonary Fibrosis.
AB - Recently, the US Food and Drug Administration (FDA) approved the first two drugs
(pirfenidone and nintedanib) indicated for the treatment of idiopathic pulmonary
fibrosis (IPF). The purpose of this analysis was to leverage publicly available
data to quantify comparative efficacy of compounds that are approved or in
development. An analysis-ready database was developed, and the analysis dataset
is composed of summary-level data from 43 arms in 20 trials, with treatment
durations ranging from 8-104 weeks. A hierarchical multivariable regression model
with nonparametric placebo estimation was used to fit the longitudinal profile of
change from baseline of percent predicted forced vital capacity (%predicted FVC)
data. Pirfenidone and nintedanib were the only drugs identified to have
significant estimated positive treatment effects. Model simulations were
performed to further evaluate the covariate and time course of treatment effects
on longitudinal change from baseline %predicted FVC to inform future trial
designs and support decision making.
PMID- 28699196
TI - Cytokeratin-positive folliculo-stellate cells in chicken adenohypophysis.
AB - Folliculo-stellate (FS) cells are non-endocrine cells found in the
adenohypophysis and are identified in many animals by the S100 protein marker.
Although keratin is another FS marker in several animals, there is no information
on localization of keratin in the avian adenohypophysis. In this study,
localization of cytokeratin in chicken adenohypophyseal cells was investigated
immunohistochemically. Basic cytokeratin (bCK)-positive cells were arranged
radially in the cell cords with their cytoplasmic processes reaching the basal
lamina. The cell bodies encircled a follicle in the center of the cell cord.
Furthermore, the bCK-positive cells were also S100B-positive. Growth hormone,
prolactin, adrenocorticotrophic hormone, and luteinizing hormone beta-subunit did
not co-localize with the bCK-positive cells. In addition, the bCK-positive cells
had a laminin-positive area in their cytoplasm. Transmission electron microscopy
observed agranular cells equipped with several microvilli that encircled a
follicle. These results indicate that bCK-positive cells in the chicken
adenohypophysis may be a predominant FS cell population and produce laminin. It
is suggested that they function as sustentacular cells to sustain the adjacent
endocrine cells and the structure of the cell cords in the chicken
adenohypophysis.
PMID- 28699197
TI - Sperm telomere length in motile sperm selection techniques: A qFISH approach.
AB - Several studies have associated telomere shortening with alterations in
reproductive function. The objective of the present study was to determine
telomere length (TL) in spermatozoa selected by either density-gradient
centrifugation (DGC) or swim-up. The analysis of TL was performed using
quantitative fluorescent in situ hybridisation (qFISH) using PNA probes in
combination with a chromatin decompaction protocol in sperm cells. Results of TL
were 24.64 +/- 5.00 Kb and 24.95 +/- 4.60 Kb before and after DGC, respectively,
and 19.59 +/- 8.02 Kb and 20.22 +/- 5.18 Kb before and after swim-up
respectively. Sperm selected by DGC or swim-up did not show any significant
differences in TL as compared to nonselected sperm (p > .05). Negative
correlations between TL and sperm motility (r = -.308; p = .049) and
concentration (r = -.353; p = .028) were found. Furthermore, exposure of sperm to
increasing concentrations of hydrogen peroxide during incubation resulted in a
reduction in TL. These data indicate that oxidative stress may be one of the main
factors involved in the reduction of TL in sperm. Preliminary clinical results
from patients included in this study indicate that TL was shorter in spermatozoa
from couples who never achieved a pregnancy compared to couples who did achieve
at least one natural pregnancy (p < .05); however, the clinical utility of this
biomarker still needs to be confirmed in further studies.
PMID- 28699198
TI - In reference to Pediatric endoscopic ear surgery in clinical practice: Lessons
learned and early outcomes.
PMID- 28699199
TI - Omega-6 polyunsaturated fatty acids, serum zinc, delta-5- and delta-6-desaturase
activities and incident metabolic syndrome.
AB - BACKGROUND: The associations of n-6 polyunsaturated fatty acids (PUFA) with
metabolic syndrome have been poorly explored. We investigated the associations of
the serum n-6 PUFA and the activities of enzymes involved in the PUFA metabolism,
delta-5-desaturase (D5D) and delta-6-desaturase (D6D) with risk of incident
metabolic syndrome. We also investigated whether zinc, a cofactor for these
enzymes, modifies these associations. METHODS: A prospective follow-up study was
conducted on 661 men who were aged 42-60 years old at baseline in 1984-1989 and
who were re-examined in 1998-2001. RESULTS: Men in the highest versus the lowest
serum total omega-6 PUFA tertile had a 70% lower multivariate-adjusted risk of
incident metabolic syndrome [odds ratio (OR) = 0.30; 95% confidence interval (CI)
= 0.18-0.51, Ptrend < 0.001]. Inverse associations were also observed for
linoleic acid, arachidonic acid and D5D activity. By contrast, men in the highest
tertile of D6D activity had an 84% higher risk (OR = 1.84; 95% CI = 1.15-2.94,
Ptrend = 0.008). Similar associations were observed with many of the metabolic
syndrome components at the re-examinations. Most associations were attenuated
after adjustment for body mass index. Finally, the associations of D6D and LA
were stronger among those with a higher serum zinc concentration. CONCLUSIONS:
Higher serum total n-6 PUFA, linoleic acid and arachidonic acid concentrations
and D5D activity were associated with a lower risk of developing metabolic
syndrome and higher D6D activity was associated with a higher risk. The role of
zinc also needs to be investigated in other populations.
PMID- 28699200
TI - Ultrasonographic features of insulinoma in six ferrets.
AB - Insulinoma is a functional, insulin-secreting tumor, arising from the beta islet
cells of the pancreas. It is one of the most common neoplasms in ferrets and has
been associated with clinical signs of hypoglycemia, such as ptyalism, pawing at
the mouth, seizures, lethargy, and coma. The ultrasonographic features of
insulinoma in ferrets have not been previously reported. The purpose of this
retrospective case series study was to describe the ultrasonographic features of
confirmed insulinoma in a group of ferrets. Inclusion criteria were abdominal
ultrasound examination and histological confirmed insulinoma by surgical biopsy.
Six ferrets met the inclusion criteria, all of which had multiple hypoglycemic
episodes. Ultrasonographic images were reviewed and the characteristics of the
pancreatic nodules were recorded. Twenty-eight pancreatic nodules were observed
in the six ferrets and were primarily hypoechoic (89.3%, 25/28) and homogenous
(46.4%, 13/28) with a smooth margin (78.6%, 22/28). The distribution of the
pancreatic nodules was 46.4% in the left lobe, 50% in the right lobe, and 3.6% in
the body of the pancreas. The sizes of the pancreatic nodules varied from 1.5 *
1.5 to 4.1 * 5.6 mm. All of the pancreatic nodules removed from surgery were
histopathologically confirmed as insulinoma. The findings indicated that
insulinoma in ferrets could be detected through ultrasonography, which may
facilitate diagnosis and preoperative surgical planning.
PMID- 28699201
TI - Characterization of Sugar and Polyphenolic Diversity in Floral Nectar of
Different 'Oblacinska' Sour Cherry Clones.
AB - 'Oblacinska' sour cherry, an autochthonous cultivar, is the most planted cultivar
in Serbian orchards. Since fruit trees in temperate zone reward insects by
producing nectar which 'quality' affects the efficiency of insect pollination,
the aim of this study was analyzing of sugars and polyphenolics in floral nectar
of 16 'Oblacinska' sour cherry clones with different yielding potential. The
contents of sugars and sugar alcohols were analyzed by ion chromatography, while
polyphenolic profile was established using liquid chromatography/mass
spectrometry technique. Fourteen sugars and six sugar alcohols were detected in
nectar samples and the most abundant were fructose, glucose, and sucrose. Eleven
polyphenols were quantified using available standards, while another 17 were
identified according to their exact masses and characteristic fragmentations.
Among quantified polyphenols, rutin, naringenin, and chrysin were the most
abundant in nectar. Principal component analysis showed that some polyphenol
components (naringin, naringenin, and rutin) together with sugars had high impact
of spatial distribution of nectar samples on score plot.
PMID- 28699202
TI - Ductal adenocarcinoma of the prostate: Clinical and biological profiles.
AB - BACKGROUND: Ductal adenocarcinoma (DAC) is a rare and aggressive subtype of
prostate cancer (PCa). In the present study, we analyzed the clinical and
biological characteristics of DAC, in comparison with high grade conventional
acinar PCa. METHODS: Samples and data were retrospectively collected from seven
institutions and centrally reviewed. Immunohistochemistry was performed on tissue
microarrays to assess the expression of candidate proteins, based on the
molecular classification of PCa, including ERG, PTEN, and SPINK1. SPOP mutations
were investigated from tumor DNA by Sanger sequencing. Relationships with outcome
were analyzed using log-rank analysis and multivariable Cox regression. RESULTS:
Among 56 reviewed prostatectomy specimens, 45 cases of DAC were finally
confirmed. The pathological stage was pT3 in more than 66% of cases. ERG was
expressed in 42% of DAC, SPINK1 in 9% (all ERG-negative), and two cases (ERG
negative) harbored a SPOP mutation. Compared to high grade conventional PCa
matched for the pathological stage, cell proliferation was higher (P = 0.04) in
DAC, and complete PTEN loss more frequent (P = 0.023). In multivariate analysis,
SPINK1 overexpression (P = 0.017) and loss of PSA immunostaining (P = 0.02) were
significantly associated with biochemical recurrence. CONCLUSION: these results
suggest that, despite biological differences that highlighted DAC aggressiveness,
the molecular classification recently proposed in conventional PCa could also be
applied in DAC.
PMID- 28699203
TI - In reference to To image or not to Image? A cost-effectiveness analysis of MRI
for patients with asymmetric sensorineural hearing loss.
PMID- 28699204
TI - Postnatal risk factors for testicular cancer: The EPSAM case-control study.
AB - Testicular cancer is considered to originate from an impaired differentiation of
fetal germ cells, but puberty could represent another time window of
susceptibility. Our study aimed at investigating the association between
environmental exposures acting during puberty/adolescence (13-19 years of age)
and the risk of testicular cancer. We used data of the EPSAM study, a case
control study on germ-cell testicular cancer conducted in the province of Turin,
Italy, involving cases diagnosed between 1997 and 2008. Histologically confirmed
cases (n = 255) and controls (n = 459) completed a postal questionnaire focusing
in particular on the pubertal period (namely age 13 years) with questions on
physical activity (competitive sports, gardening), lifestyle (alcohol
consumption, smoking), occupational history and medical conditions. All analyses
were adjusted for the matching variables, cryptorchidism and educational level.
Having done at least one competitive sport during puberty (odds ratio [OR]: 0.72,
95% confidence interval: 0.52-1.00), gardening activities during puberty (OR:
0.62, 0.42-0.94) and having a lower weight than peers during puberty (OR: 0.64,
0.42-0.97) were all inversely associated with the risk of testicular cancer. No
evidence of association between smoking or alcohol consumption during puberty and
the risk of testicular cancer was observed. Regarding agriculture-related
occupations, we found an association with the risk of testicular cancer both for
occasional jobs during puberty (OR: 2.40, 95% CI: 1.08-5.29) and ever employment
in adolescence (OR: 2.59, 95% CI: 0.83-8.10). Our results suggest that postnatal
exposures could play a role in testicular cancer aetiology, at least when acting
in puberty or adolescence.
PMID- 28699205
TI - Native kinesin-1 does not bind preferentially to GTP-tubulin-rich microtubules in
vitro.
AB - Molecular motors such as kinesin-1 work in small teams to actively shuttle cargos
in cells, for example in polarized transport in axons. Here, we examined the
potential regulatory role of the nucleotide state of tubulin on the run length of
cargos carried by multiple kinesin motors, using an optical trapping-based in
vitro assay. Based on a previous report that kinesin binds preferentially to GTP
tubulin-rich microtubules, we anticipated that multiple-kinesin cargos would run
substantially greater distances along GMPCPP microtubules than along GDP
microtubules. Surprisingly, we did not uncover any significant differences in run
length between microtubule types. A combination of single-molecule experiments,
comparison with previous theory, and classic microtubule affinity pulldown assays
revealed that native kinesin-1 does not bind preferentially to GTP-tubulin-rich
microtubules. The apparent discrepancy between our observations and the previous
report likely reflects differences in post-translational modifications between
the native motors used here and the recombinant motors examined previously.
Future investigations will help shed light on the interplay between the motor's
post-translational modification and the microtubule's nucleotide-binding state
for transport regulation in vivo.
PMID- 28699206
TI - KIAA1199: A novel regulator of MEK/ERK-induced Schwann cell dedifferentiation.
AB - The molecular mechanisms that regulate Schwann cell (SC) plasticity and the role
of the Nrg1/ErbB-induced MEK1/ERK1/2 signalling pathway in SC dedifferentiation
or in myelination remain unclear. It is currently believed that different levels
of MEK1/ERK1/2 activation define the state of SC differentiation. Thus, the
identification of new regulators of MEK1/ERK1/2 signalling could help to decipher
the context-specific aspects driving the effects of this pathway on SC
plasticity. In this perspective, we have investigated the potential role of
KIAA1199, a protein that promotes ErbB and MEK1/ERK1/2 signalling in cancer
cells, in SC plasticity. We depleted KIAA1199 in the SC-derived MSC80 cell line
with RNA-interference-based strategy and also generated Tamoxifen-inducible and
conditional mouse models in which KIAA1199 is inactivated through homologous
recombination, using the Cre-lox technology. We show that the invalidation of
KIAA1199 in SC decreases the expression of cJun and other negative regulators of
myelination and elevates Krox20, driving them towards a pro-myelinating
phenotype. We further show that in dedifferentiation conditions, SC invalidated
for KIAA1199 exhibit lower myelin clearance as well as increased myelination
capacity. Finally, the Nrg1-induced activation of the MEK/ERK/1/2 pathway is
severely reduced when KIAA1199 is absent, indicating that KIAA1199 promotes Nrg1
dependent MEK1 and ERK1/2 activation in SCs. In conclusion, this work identifies
KIAA1199 as a novel regulator of MEK/ERK-induced SC dedifferentiation and
contributes to a better understanding of the molecular control of SC
dedifferentiation.
PMID- 28699207
TI - Supplemental effect of different levels of taurine in Modena on boar semen
quality during liquid preservation at 17 degrees C.
AB - Peroxidation damage induces sublethal injury to boar sperm during the storage
process. Taurine has already been demonstrated to protect cells effectively from
oxidant-induced injury. This study was aimed to evaluate the effect of different
concentrations of taurine (0.5, 1, 5 and 10 mmol/L) in Modena diluent on boar
sperm quality during liquid storage at 17 degrees C. Ejaculates from sexually
mature Duroc pigs were collected, pooled and preserved in the Modena containing
different concentrations of taurine. Sperm motility, plasma membrane integrity,
acrosome integrity, total antioxidative capacity (T-AOC) activity and
malondialdehyde content (MDA) were examined every 24 h. Modena diluent containing
taurine suppressed the reduction in sperm qualities during the process of liquid
preservation compared with those of the control group. After 5 days of liquid
preservation, the addition of taurine at 5 mmol/L had the optimal effect on
survival time as well as maintenance of motility, plasma membrane integrity,
acrosomal integrity, T-AOC activity and MDA content. These results may suggest
the possibility that the proper addition of taurine to the semen extender
improves the swine production system using artificial insemination by the
suppressing of sperm damage and subsequent dysfunction during liquid
preservation.
PMID- 28699208
TI - Being in a standstill-of-life: women's experience of being diagnosed with
systemic lupus erythematosus: a hermeneutic-phenomenological study.
AB - Systemic lupus erythematosus (SLE) is a highly unpredictable and potentially
lethal disease which ultimately challenges identity, future and the meaning of
life. In a caring context, the experience of good health is perceived to be a
balance between biomedical health and the existential experience of having a good
life. This balance is jeopardised in the face of severe chronic illness and leads
to extensive suffering if not handled carefully. Research suggests that patients
suffering from severe chronic illness need support on an existential level, but
also emphasises that, given its elusive nature, caring for the existential
dimension is difficult to manage. This paper explores the experience of being
diagnosed with SLE as an existential phenomenon. Through repeated
phenomenological and hermeneutic interviews with 15 women conducted from 2013 to
2015, data concerning the diagnostic phase of SLE were analysed using Van Manen's
phenomenology of practice. The essence was found to be a standstill in life
comprehended through three inter-related themes: standing in a swirl of events,
standing on uneven ground and standing at a turning point with oneself and
others. The paper elucidates how existential life phenomena are lived, during the
course of being diagnosed. In conclusion, it provides an ethical awareness of how
a standstill in life is lived and of the patients' existential transition during
the diagnostic phase. A holistic approach is recommended in caring for patients
with SLE.
PMID- 28699209
TI - Gradual changes in range size accompany long-term trends in species richness.
AB - Species richness has long been used as an indicator of ecosystem functioning and
health. Global richness is declining, but it is unclear whether sub-global trends
differ. Regional trends are especially understudied, with most focused on island
regions where richness is strongly impacted by novel colonisations. We addressed
this knowledge gap by testing for multi-decade trends in species richness in nine
open marine regions around North America (197 region-years) while accounting for
imperfect observations and grounding our findings in species-level range
dynamics. We found positive richness trends in eight of nine regions, four of
which were statistically significant. Species' range sizes generally contracted
pre-extinction and expanded post-colonisation, but the ranges of transient
species expanded over the long-term, slowly increasing their regional retention
and driving increasing richness. These results provide more evidence that sub
global richness trends are stable or increasing, and highlight the utility of
range size for understanding richness dynamics.
PMID- 28699210
TI - Driving in search of analyses.
AB - Although transportation safety has greatly improved over the past 2 decades,
motor vehicle crash injuries remain a leading cause of morbidity and mortality,
particularly among young drivers. Driver errors and behaviors such as speeding
and distraction contribute disproportionately to crashes among inexperienced
novices, who develop safe driving judgment only with substantial driving
experience, commonly described as the "young driver problem." Research on young
drivers has applied a range of research methods, including analyses of national
archival data (mainly from police reports), crash analyses, observation of driver
behavior, surveys of driver behavior and dispositions, and experimental research
on driver behavior and vehicle crash worthiness. Prominent research questions
regarding young driver safety include what and how do novices learn to drive
safely, what are the predictors of young driver crashes, what is the variability
and overtime trajectories of young driver performance and outcomes, and to what
extent is the young driver problem due mainly to average population risk or high
risk groups? Current research on young drivers is complicated by small sample
sizes, relatively rare events, high within and between group variability, missing
data, the need to estimate exposure, and the lack of longitudinal and
experimental designs, problems that require complex analytic methods. In this
paper, we provide an overview of driving research methods, examples of research
addressing the young driver problem, and examples of statistical collaboration on
young driver research, focusing particularly on estimating prediction of crash
risk and estimating variability in young driver performance and outcomes.
PMID- 28699211
TI - Better and faster velocity pulsatility assessment in cerebral white matter
perforating arteries with 7T quantitative flow MRI through improved slice
profile, acquisition scheme, and postprocessing.
AB - PURPOSE: A previously published cardiac-gated 2D Qflow protocol at 7 T in
cerebral perforating arteries was optimized to reduce velocity underestimation
and improve temporal resolution. METHODS: First, the signal-to-noise ratio (SNR)
gain of the velocity measurement (SNRv ) was tested for two signal averages
versus one. Second, the decrease in velocity underestimation with a tilted
optimized nonsaturating excitation (TONE) pulse was tested. Third, the decrease
in pulsatility index (PI) underestimation through improved temporal resolution
was tested. Test-retest agreement was measured for the resulting acquisition in
older volunteers (mean age 63 years), and the results were compared with the
other volunteers (mean age 26 years). RESULTS: Using two signal averages
increased SNRv by only 12% (P = 0.04), probably due to motion of the subvoxel
size arteries. The TONE decreased velocity underestimation, thereby increasing
the mean velocity from 0.52 to 0.67 cm/s (P < 0.001). The PI increased
substantially with increasing temporal resolution. The test-retest agreement
showed good coefficients of repeatability of 0.18 cm/s for velocity and 0.14 for
PI. The measured velocity was lower in the older group: 0.42 versus 0.51 cm/s (P
= 0.05). CONCLUSIONS: The optimized sequence yields better velocity and PI
estimates in small vessels, has twice as good test-retest agreement, and has a
suitable scan time for use in patients. Magn Reson Med 79:1473-1482, 2018. (c)
2017 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals,
Inc. on behalf of International Society for Magnetic Resonance in Medicine. This
is an open access article under the terms of the Creative Commons Attribution
NonCommercial License, which permits use, distribution and reproduction in any
medium, provided the original work is properly cited and is not used for
commercial purposes.
PMID- 28699212
TI - Fetal megacystis: Institutional experience and outcomes.
AB - BACKGROUND: Fetal megacystis is a sonographic feature that may be indicative of
several underlying pathologies. Despite advances in diagnosis and management, the
overall prognosis of affected fetuses remains poor and about 50% of such
pregnancies are terminated. AIMS: To define the frequency, management, survival
and renal outcomes of fetal megacystis over nine years at Wellington Hospital,
New Zealand. MATERIALS AND METHODS: A nine-year retrospective review of fetuses
with an antenatal diagnosis of megacystis was undertaken. RESULTS: Sixteen cases
were identified (nine live births, five terminations and two perinatal deaths).
This gives an observed frequency of one per 940 fetuses scanned. Two-thirds of
the live births have survived and been followed for a mean of 5.3 years. None
have required renal dialysis or transplantation to date. CONCLUSIONS: The current
series contributes to our knowledge of fetal megacystis and helps to inform
antenatal counselling. Improved prognostic criteria are urgently required to
accurately differentiate between fetuses with favourable versus poor outcomes.
PMID- 28699213
TI - Acetamide Derivatives of Chromen-2-ones as Potent Cholinesterase Inhibitors.
AB - Alzheimer's disease (AD), a neurodegenerative disorder, is a serious medical
issue worldwide with drastic social consequences. Inhibition of cholinesterase is
one of the rational and effective approaches to retard the symptoms of AD and,
hence, consistent efforts are being made to develop efficient anti-cholinesterase
agents. In pursuit of this, a series of 19 acetamide derivatives of chromen-2
ones were synthesized and evaluated for their acetylcholinesterase (AChE) and
butyrylcholinesterase (BChE) inhibitory potential. All the synthesized compounds
exhibited significant anti-AChE and anti-BChE activity, with IC50 values in the
range of 0.24-10.19 MUM and 0.64-30.08 MUM, respectively, using donepezil
hydrochloride as the standard. Out of 19 compounds screened, 3 compounds, viz.
22, 40, and 43, caused 50% inhibition of AChE at 0.24, 0.25, and 0.25 MUM,
respectively. A kinetic study revealed them to be mixed-type inhibitors, binding
with both the CAS and PAS sites of AChE. The above-selected compounds were found
to be effective inhibitors of AChE-induced and self-mediated Abeta1-42
aggregation. ADMET predictions demonstrated that these compounds may possess
suitable blood-brain barrier (BBB) permeability. Hemolytic assay results revealed
that these compounds did not lyse human RBCs up to a thousand times of their IC50
value. MTT assays performed for the shortlisted compounds showed them to be
negligibly toxic after 24 h of treatment with the SH-SY5Y neuroblastoma cells.
These results provide insights for further optimization of the scaffolds for
designing the next generation of compounds as lead cholinesterase inhibitors.
PMID- 28699214
TI - Understanding the effects of topography on skin moisturization measurement via
two-dimensional capacitance imaging.
AB - OBJECTIVE: Methods which assess skin moisturization based on changes in its
electrical properties are widely used in both cosmetic and medical research
industries. However, the devices themselves often give results which are
significantly different to each other. Recently two-dimensional imaging
moisturization systems have become commercially available, which have the
capability to provide a more detailed assessment of what is contributing to
measured skin moisturization. Presented here is a new in vitro method for
preparing textured model test substrates for use with these devices, and results
of their use to provide a clearer insight into the devices operation. METHODS: A
variety of different textured model test substrates were measured using a
commercially available skin moisturization measurement device, the Epsilon. The
response of the Epsilon was also tested against conventional skin moisturization
devices. RESULTS: Surface morphology of model test substrates was found to have a
significant influence on the measurement of its electrical properties with both
the conventional and two-dimensional skin moisturization measurement devices.
Through modification of the areas of the image being assessed for the two
dimensional moisturization mapping device, the parts of the model test substrate
in contact with the device were indentified and analysed separately to areas not
in contact with the sensor. This provided a more robust assessment of the
electrical properties of substrate itself, rather than being influenced by
texture like the conventional skin moisturization measurement devices.
CONCLUSIONS: While the two-dimensional moisturization mapping systems can be used
like a conventional electrical skin measurement device giving a simple overall
reading of skin moisturization for the test area, their true value over existing
electrical measures comes from its ability to isolate the skin itself from areas
which are not in contact with the sensor.
PMID- 28699215
TI - Automated T2 relaxometry of the hippocampus for temporal lobe epilepsy.
AB - OBJECTIVE: Hippocampal sclerosis (HS), the most common cause of refractory
temporal lobe epilepsy, is associated with hippocampal volume loss and increased
T2 signal. These can be identified on quantitative imaging with hippocampal
volumetry and T2 relaxometry. Although hippocampal segmentation for volumetry has
been automated, T2 relaxometry currently involves subjective and time-consuming
manual delineation of regions of interest. In this work, we develop and validate
an automated technique for hippocampal T2 relaxometry. METHODS: Fifty patients
with unilateral or bilateral HS and 50 healthy controls underwent T1 -weighted
and dual-echo fast recovery fast spin echo scans. Hippocampi were automatically
segmented using a multi-atlas-based segmentation algorithm (STEPS) and a template
database. Voxelwise T2 maps were determined using a monoexponential fit. The
hippocampal segmentations were registered to the T2 maps and eroded to reduce
partial volume effect. Voxels with T2 >170 msec excluded to minimize
cerebrospinal fluid (CSF) contamination. Manual determination of T2 values was
performed twice in each subject. Twenty controls underwent repeat scans to assess
interscan reproducibility. RESULTS: Hippocampal T2 values were reliably
determined using the automated method. There was a significant ipsilateral
increase in T2 values in HS (p < 0.001), and a smaller but significant
contralateral increase. The combination of hippocampal volumes and T2 values
separated the groups well. There was a strong correlation between automated and
manual methods for hippocampal T2 measurement (0.917 left, 0.896 right, both p <
0.001). Interscan reproducibility was superior for automated compared to manual
measurements. SIGNIFICANCE: Automated hippocampal segmentation can be reliably
extended to the determination of hippocampal T2 values, and a combination of
hippocampal volumes and T2 values can separate subjects with HS from healthy
controls. There is good agreement with manual measurements, and the technique is
more reproducible on repeat scans than manual measurement. This protocol can be
readily introduced into a clinical workflow for the assessment of patients with
focal epilepsy.
PMID- 28699216
TI - Activation of Remote meta-C-H Bonds in Arenes with Tethered Alcohols: A
Salicylonitrile Template.
AB - Palladium-catalyzed activation of remote meta-C-H bonds in arenes containing
tethered alcohols was achieved with high regioselectivity by using a nitrile
template. Computational studies on the macrocyclic transition state of the
regioselectivity-determining C-H activation steps revealed that both the C-N-Ag
angles and gauche comformations of phenyl ether play an extremely important role
in the meta selectivity.
PMID- 28699217
TI - Infection Risk With Biologic Therapy in Patients With Inflammatory Bowel Disease.
AB - The development of biologic drugs revolutionized the management of inflammatory
bowel diseases: Crohn's disease and ulcerative colitis. However, while their
efficacy has been well established, it remains uncertain to what extent biologic
treatments may be associated with important safety risks, such as serious
infections, opportunistic infections, or tuberculosis reactivation. Herein, we
review and discuss the current evidence on the infection risk associated with
biologic therapy in patients with inflammatory bowel disease (IBD).
PMID- 28699218
TI - Impaired corticomuscular coherence during isometric elbow flexion contractions in
humans with cervical spinal cord injury.
AB - After spinal cord injury (SCI), the reorganization of the neuromuscular system
leads to increased antagonist muscles' co-activation-that is, increased
antagonist vs. agonist muscles activation ratio-during voluntary contractions.
Increased muscle co-activation is supposed to result from reduced cortical
influences on spinal mechanisms inhibiting antagonist muscles. The assessment of
the residual interactions between cortical and muscles activity with
corticomuscular coherence (CMC) in participants with SCI producing different
force levels may shed new lights on the regulation of muscle co-activation. To
achieve this aim, we compared the net joint torque, the muscle co-activation and
the CMC ~ 10 and ~ 20 Hz with both agonist and antagonist muscles in participants
with SCI and healthy participants performing actual isometric elbow flexion
contractions at three force levels. For all participants, overall CMC and muscle
co-activation decreased with the increase in the net joint torque, but only CMC ~
10 Hz was correlated with muscle co-activation. Participants with SCI had greater
muscle co-activation and lower CMC ~ 10 Hz, at the highest force levels. These
results emphasize the importance of CMC as a mechanism that could take part in
the modulation of muscle co-activation to maintain a specific force level. Lower
CMC ~ 10 Hz in SCI participants may reflect the decreased cortical influence on
spinal mechanisms, leading to increased muscle co-activation, although plasticity
of the corticomuscular coupling seems to be preserved after SCI to modulate the
force level. Clinically, the CMC may efficiently evaluate the residual integrity
of the neuromuscular system after SCI and the effects of rehabilitation.
PMID- 28699219
TI - Enzyme Prodrug Therapy Engineered into Electrospun Fibers with Embedded Liposomes
for Controlled, Localized Synthesis of Therapeutics.
AB - Enzyme prodrug therapy (EPT) enables localized conversion of inert prodrugs to
active drugs by enzymes. Performance of EPT necessitates that the enzyme remains
active throughout the time frame of the envisioned therapeutic application. beta
glucuronidase is an enzyme with historically validated performance in EPT,
however it retains its activity in biomaterials for an insufficiently long period
of time, typically not exceeding 7 d. Herein, the encapsulation of beta
glucuronidase in liposomal subcompartments within poly(vinyl alcohol) electrospun
fibers is reported, leading to the assembly of biocatalytically active materials
with activity of the enzyme sustained over at least seven weeks. It is further
shown that liposomes provide the highly beneficial stabilization of the enzyme
when incubated in cell culture media. The assembled biocatalytic materials
successfully produce antiproliferative drugs (SN-38) using externally
administered prodrugs (SN-38-glucuronide) and effectively suppress cell
proliferation, with envisioned utility in the design of cardiovascular grafts.
PMID- 28699220
TI - Melanin pigmentation and melanoma.
PMID- 28699222
TI - In vitro fungicidal effects of methylene blue at 625-nm.
AB - The aim of the study is to confirm the effectiveness of photodynamic therapy
(PDT) as a significant inhibitor of Trichophyton rubrum (T. rubrum) and to
determine the most appropriate dose and rate of delivery. Trichophyton rubrum is
the most common dermatophyte worldwide, responsible for the majority of
superficial fungal infections. The traditional treatment of T. rubrum has known
adverse effects. An alternative treatment is warranted. Photosensitised T. rubrum
specimens were treated with 625-nm light at doses of 3, 12, 24, 40 and 60 J/cm2 .
Colony counts were performed and compared to untreated controls. Doses of 24, 40
and 60 J/cm2 all produced kill rates of over 94%. A lower rate of delivery (7.80
mW/cm2 ) was shown to be a greater inhibitor of T. rubrum than a higher rate of
delivery (120 mW/cm2 ). Photodynamic therapy with methylene blue (MB) at 625 nm
using a low rate of delivery at doses of 24, 40 and 60 J/cm2 is an effective
inhibitor of T. rubrum. A rate of delivery of 7.80 mW/cm2 is a significantly
greater inhibitor of T. rubrum than a rate of 120 mW/cm2 when applying 625-nm
light in PDT using MB.
PMID- 28699223
TI - Outcomes of head and neck cancer surgery in the geriatric population based on
case volume at academic centers.
AB - OBJECTIVES/HYPOTHESIS: Evaluate the impact of case volume and other variables on
cost and mortality after head and neck oncologic surgery in the geriatric
population. STUDY DESIGN: Cross-sectional study. METHODS: The Vizient database
was accessed for data on geriatric patients (age >=65 years) who underwent
surgery for head and neck cancers (excluding thyroid and skin cancer) at full
member academic medical centers between 2009 and 2012. Multivariate, linear
regression analyses, chi2 tests, and analysis of variance were applied to
evaluate significant associations between hospital case volume and independent
variables including cost, cost index, mortality, mortality index, length of stay,
length of stay index, and readmission rates. RESULTS: A total of 4,544 patients
were included. Total length of stay was 6.72 days in high-volume hospitals,
compared to 8.12 days and 7.91 days in moderate- and low-volume hospitals,
respectively (P = .0144). Frequency of intensive care unit stays was 36.5% in
high-volume hospitals, compared to 42.19% and 40.29% in moderate- and low-volume
hospitals, respectively (P = .0048). Mortality (0.78%) and average cost per case
($21,834) was lower, but nonsignificant in high-volume hospitals. Using multiple
regression analysis, major severity of disease was positively associated with
complication rate (P < .0001) and length of stay (P = .0481). CONCLUSIONS: After
controlling for other factors, high-volume academic medical centers have a lower
intensive care unit stay, but no difference in mortality or average cost per case
when compared to low-volume hospitals. LEVEL OF EVIDENCE: 2b. Laryngoscope,
127:2539-2544, 2017.
PMID- 28699224
TI - Melt Electrospinning Writing of Poly-Hydroxymethylglycolide-co-epsilon
Caprolactone-Based Scaffolds for Cardiac Tissue Engineering.
AB - Current limitations in cardiac tissue engineering revolve around the inability to
fully recapitulate the structural organization and mechanical environment of
native cardiac tissue. This study aims at developing organized ultrafine fiber
scaffolds with improved biocompatibility and architecture in comparison to the
traditional fiber scaffolds obtained by solution electrospinning. This is
achieved by combining the additive manufacturing of a hydroxyl-functionalized
polyester, (poly(hydroxymethylglycolide-co-epsilon-caprolactone) (pHMGCL), with
melt electrospinning writing (MEW). The use of pHMGCL with MEW vastly improves
the cellular response to the mechanical anisotropy. Cardiac progenitor cells
(CPCs) are able to align more efficiently along the preferential direction of the
melt electrospun pHMGCL fiber scaffolds in comparison to electrospun poly(epsilon
caprolactone)-based scaffolds. Overall, this study describes for the first time
that highly ordered microfiber (4.0-7.0 um) scaffolds based on pHMGCL can be
reproducibly generated with MEW and that these scaffolds can support and guide
the growth of CPCs and thereby potentially enhance their therapeutic potential.
PMID- 28699225
TI - Intensive consolidation with G-CSF support: Tolerability, safety, reduced
hospitalization, and efficacy in acute myeloid leukemia patients >=60 years.
AB - The aim of this study was to evaluate the efficacy and feasibility of intensified
consolidation therapy employing fludarabine and ARA-C in cycle 1 and intermediate
dose ARA-C (IDAC) in cycles 2 through 4, in elderly acute myeloid leukemia (AML)
patients and to analyze the effects of pegfilgrastim on the duration of
neutropenia, overall toxicity, and hospitalization-time during consolidation in
these patients. Thirty nine elderly patients with de novo AML (median age 69.9
years) who achieved complete remission (CR) after induction-chemotherapy were
analyzed. To examine the effect of pegfilgrastim on neutropenia and
hospitalization, we compared cycles 2 and 4 where pegfilgrastim was given
routinely from day 6 (IDAC-P) with cycle 3 where pegfilgrastim was only
administered in case of severe infections and/or prolonged neutropenia. All four
planned cycles were administered in 23/39 patients (59.0%); 5/39 patients (12.8%)
received 3 cycles, 3/39 (7.7%) 2 cycles, and 8/39 (20.5%) one consolidation
cycle. The median duration of severe neutropenia was 7 days in cycle 2 (IDAC-P),
11.5 days in cycle 3 (IDAC), and 7.5 days in cycle 4 (IDAC-P) (P < .05). Median
overall survival was 1.1 years and differed significantly between patients aged
<75 and >=75 years (P < .05). The probability to be alive after 5 years was 32%.
Together, intensified consolidation can be administered in AML patients >=60, and
those who are <75 may benefit from this therapy. Routine administration of
pegfilgrastim during consolidation shortens the time of neutropenia and
hospitalization in these patients.
PMID- 28699226
TI - Epstein-Barr virus (EBV) provides survival factors to EBV+ diffuse large B-cell
lymphoma (DLBCL) lines and modulates cytokine induced specific chemotaxis in EBV+
DLBCL.
AB - Diffuse large B-cell lymphoma (DLBCL), the most common type of malignant
lymphoma, accounts for 30% of adult non-Hodgkin lymphomas. Epstein-Barr virus
(EBV) -positive DLBCL of the elderly is a newly recognized subtype that accounts
for 8-10% of DLBCLs in Asian countries, but is less common in Western
populations. Five DLBCL-derived cell lines were employed to characterize patterns
of EBV latent gene expression, as well as response to cytokines and chemotaxis.
Interleukin-4 and interleukin-21 modified LMP1, EBNA1 and EBNA2 expression
depending on cell phenotype and type of EBV latent programme (type I, II or III).
These cytokines also affected CXCR4- or CCR7-mediated chemotaxis in two of the
cell lines, Farage (type III) and Val (type II). Further, we investigated the
effect of EBV by using dominant-negative EBV nuclear antigen 1(dnEBNA1) to
eliminate EBV genomes. This resulted in decreased chemotaxis. By employing an
alternative way to eliminate EBV genomes, Roscovitine, we show an increase of
apoptosis in the EBV-positive lines. These results show that EBV plays an
important role in EBV-positive DLBCL lines with regard to survival and
chemotactic response. Our findings provide evidence for the impact of
microenvironment on EBV-carrying DLBCL cells and might have therapeutic
implications.
PMID- 28699227
TI - Implication of chemo-resistant memory T cells for immune surveillance in patients
with sarcoma receiving chemotherapy.
AB - Chemotherapy has improved the prognosis of patients with sarcomas. However, it
may suppress anti-tumor immunity. Recently, we reported a novel CD8+ memory T
cell population with a chemo-resistance property, "young memory" T (TYM ) cells.
In this study, we investigated the proportion and function of TYM cells in
peripheral blood of healthy donors and sarcoma patients who received chemotherapy
and those who did not. The proportion of TYM cells was significantly decreased in
patients compared with that in healthy donors. In healthy donors, anti-EBV CTLs
were induced using mixed lymphocyte peptide culture, from not only TYM cells but
also TCM and TEM cells. No CTLs directed to tumor-associated antigens were
induced. In sarcoma patients who did not receive chemotherapy, in addition to
anti-EBV CTLs, CTLs directed to the tumor-associated antigen PBF were induced
from TYM , TCM and TEM cells. In sarcoma patients who received chemotherapy, EBV
specific CTLs were induced from TYM cells but were hardly induced from TEM cells.
Interestingly, CTLs directed to the anti-tumor-associated antigen PBF were
induced from TYM cells but not from the TCM and TEM cells in sarcoma patients who
received chemotherapy. The findings suggest that TYM cells are resistant to
chemotherapy and can firstly recover from the nadir. TYM cells might be important
for immunological memory, especially in sarcoma patients receiving chemotherapy.
PMID- 28699228
TI - Facilitating Active Species Generation by Amorphous NiFe-Bi Layer Formation on
NiFe-LDH Nanoarray for Efficient Electrocatalytic Oxygen Evolution at Alkaline
pH.
AB - Searching for a simple and fast strategy to effectively enhance the oxygen
evolution reaction (OER) performance of non-noble-metal electrocatalysts in
alkaline media remains a significant challenge. Herein, the OER activity of NiFe
LDH nanoarray on carbon cloth (NiFe-LDH/CC) in alkaline media is shown to be
greatly boosted by an amorphous NiFe-Borate (NiFe-Bi ) layer formation on NiFe
layered double hydroxide (NiFe-LDH) surface. Such a NiFe-LDH@NiFe-Bi /CC catalyst
electrode only needs an overpotential of 294 mV to drive 50 mA cm-2 in 1.0 m KOH;
116 mV less than that needed by NiFe-LDH/CC. Notably, this electrode also
demonstrates strong long-term electrochemical durability. The superior activity
is ascribed to the pre-formed amorphous NiFe-Bi layer effectively promoting
active species generation on the NiFe-LDH surface. This work opens up exciting
new avenues for developing high-performance water-oxidation catalyst materials
for application.
PMID- 28699229
TI - A Combined Experimental/Computational Study of the Mechanism of a Palladium
Catalyzed Bora-Negishi Reaction.
AB - Experimental and computational efforts are reported which illuminate the
mechanism of a novel boron version of the widespread Negishi coupling reaction
that offers a new protocol for the formation of aryl/acyl C-B bonds using a bulky
boryl fragment. The role of nucleophilic borylzinc reagents in the reduction of
the PdII pre-catalysts to Pd0 active species has been demonstrated. The non
innocent behavior of the PPh3 ligands of the [Pd(PPh3 )2 Cl2 ] pre-catalyst under
activation conditions has been probed both experimentally and computationally,
revealing the formation of a trimetallic Pd species bearing bridging phosphide
(PPh2- ) ligands. Our studies also reveal the monoligated formulation of the Pd0
active species, which led us to synthesize related (eta3 -indenyl)Pd
monophosphine catalysts which show improved catalytic performances under mild
conditions. A complete mechanistic proposal to aid future catalyst developments
is provided.
PMID- 28699230
TI - Short-term high-fat diet increases the presence of astrocytes in the hypothalamus
of C57BL6 mice without altering leptin sensitivity.
AB - Diet-induced obesity is associated with hypothalamic inflammation and this
phenomenon has been proposed to explain leptin resistance. In the present study,
we used a short-term high-fat diet (HFD) paradigm for 10 days and analysed the
cellular and physiological responses to leptin administration in C57BL6 mice. In
parallel, we performed glial fibrillary acidic protein immunostaining to measure
the presence of astrocytes in the arcuate nucleus of the hypothalamus (ARH) after
10 days and 20 weeks of HFD. Interestingly, the results obtained demonstrate that
the presence of star-like astrocytes is significantly increased after 10 days of
HFD, although this is not associated with the absence of cellular and
physiological response to leptin administration in mice. Taken together, the
results of the present study suggest that star-like astrocytes rapidly increase
in numbers in the ARH in response to HFD, although this phenomenon cannot explain
the development of leptin resistance by itself.
PMID- 28699231
TI - When I say ... narrative competence.
PMID- 28699233
TI - Spotlights on our sister journals: Angew. Chem. Int. Ed. 30/2017.
PMID- 28699232
TI - Acetylated Signal Transducer and Activator of Transcription 3 Functions as
Molecular Adaptor Independent of Transcriptional Activity During Human
Cardiogenesis.
AB - Activation of signal transducer and activator of transcription 3 (STAT3) is
imperative for mammalian development, specifically cardiogenesis. STAT3
phosphorylation and acetylation are key post-translational modifications that
regulate its transcriptional activity. Significance of such modifications during
human cardiogenesis remains elusive. Using human pluripotent stem cells to
recapitulate cardiogenesis, two independently modified STAT3alpha (92 kDa)
isoforms (phosphorylated and acetylated), which perform divergent functions were
identified during cardiomyocyte (CM) formation. Phosphorylated STAT3alpha
functioned as the canonical transcriptional activator, while acetylated
STAT3alpha underwent caspase-3-mediated cleavage to generate a novel STAT3zeta
fragment (~45 kDa), which acted as a molecular adaptor integral to the ErbB4
p38gamma signaling cascade in driving CM formation. While STAT3alpha knockdown
perturbed cardiogenesis by eliminating both post-translationally modified
STAT3alpha isoforms, caspase-3 knockdown specifically abrogates the function of
acetylated STAT3alpha, resulting in limited STAT3zeta formation thereby
preventing nuclear translocation of key cardiac transcription factor Nkx2-5 that
disrupted CM formation. Our findings show the coexistence of two post
translationally modified STAT3alpha isoforms with distinct functions and define a
new role for STAT3 as a molecular adaptor that functions independently of its
canonical transcriptional activity during human cardiogenesis. Stem Cells
2017;35:2129-2137.
PMID- 28699234
TI - Investigation of morin-induced insulin secretion in cultured pancreatic cells.
AB - Morin is a flavonoid contained in guava that is known to reduce hyperglycemia in
diabetes. Insulin secretion has been demonstrated to increase following the
administration of morin. The present study is designed to investigate the
potential mechanism(s) of morin-induced insulin secretion in the MIN6 cell line.
First, we identified that morin induced a dose-dependent increase in insulin
secretion and intracellular calcium content in MIN6 cells. Morin potentiated
glucose-stimulated insulin secretion (GSIS). Additionally, we used siRNA for the
ablation of imidazoline receptor protein (NISCH) expression in MIN6 cells.
Interestingly, the effects of increased insulin secretion by morin and canavanine
were markedly reduced in Si-NISCH cells. Moreover, we used KU14R to block
imidazoline I3 receptor (I-3R) that is known to enhance insulin release from the
pancreatic beta-cells. Without influence on the basal insulin secretion, KU14R
dose-dependently inhibited the increased insulin secretion induced by morin or
efaroxan in MIN6 cells. Additionally, effects of increased insulin secretion by
morin or efaroxan were reduced by diazoxide at the dose sufficient to open KATP
channels and attenuated by nifedipine at the dose used to inhibit L-type calcium
channels. Otherwise, phospholipase C (PLC) is introduced to couple with
imidazoline receptor (I-R). The PLC inhibitor dose-dependently inhibited the
effects of morin in MIN6 cells. Similar blockade was also observed in protein
kinase C (PKC) inhibitor-treated cells. Taken together, we found that morin
increases insulin secretion via the activation of I-R in pancreatic cells.
Therefore, morin would be useful to develop in the research and treatment of
diabetic disorders.
PMID- 28699235
TI - Expression patterns of claudins in patients with triple-negative breast cancer
are associated with nodal metastasis and worse outcome.
AB - Claudins (CLDNs) are key cell adhesion molecules, which compose tight junctions
(TJs), and the disruption of TJs is associated with cancer development. Here we
immunohistochemically studied expression patterns of CLDNs in 222 primary
invasive breast cancers including 68 triple-negative breast cancers (TNBCs), and
examined their correlation with epithelial-to-mesenchymal transition (EMT)
related markers, breast cancer stem cell (BCSC) markers, and clinicopathological
features including patients' clinical outcome. Tumor margins were classified as
three infiltrating growth patterns (expanding, intermediate and infiltrating).
For CLDN1, 3, 4, and 7, their expression rates were more frequent in TNBCs than
in other subtypes (11.8% vs 0.7%, 26.5% vs 2.0%, 48.5% vs 11.1%, and 32.4% vs
8.7%, respectively; P <= 0.001). In 68 TNBCs, we identified high Ki67 labeling
index (LI) and the combination of CLDN4 high/CLDN7 low expression as independent
predictors of axillary nodal metastasis (P = 0.019; OR, 4.36; 95%CI, 1.28-14.90
and P = 0.007; OR, 5.33; 95%CI, 1.58-17.90). Moreover, the combination of CLDN1
low/CLDN7 low/E-cadherin negative as well as tumor infiltrating patterns were
predictors for worse recurrence-free survival by univariate analyses in TNBCs (P
= 0.005 and P = 0.011). Our analyses provide further evidence that CLDNs would be
valuable prognostic markers in TNBCs.
PMID- 28699236
TI - Piperonal attenuates visceral adiposity in mice fed a high-fat diet: potential
involvement of the adenylate cyclase-protein kinase A dependent pathway.
AB - SCOPE: Piperonal is an aromatic compound found in vanilla and has a floral odor
resembling vanillin. This study was aimed to test whether piperonal attenuates
visceral adiposity induced by a high-fat diet (HFD) in mice and to explore the
underlying molecular mechanisms. METHODS AND RESULTS: Male C57BL/6N mice were fed
a normal diet, HFD, or 0.05% piperonal-supplemented HFD (PSD) for 10 weeks. PSD
fed mice showed attenuation of body weight gain, total visceral fat pad weights,
and plasma lipid levels compared to HFD-fed mice. Piperonal supplementation of
the HFD increased the mRNA expression of certain isotypes of adenylate cyclase
(Adcy) and protein kinase A (PKA) in the white adipose tissue (WAT) of mice. The
adipogenesis-related genes were downregulated, whereas fatty acid oxidation- and
thermogenesis-related genes were upregulated in the WAT of PSD-fed mice compared
to those in HFD-fed mice. Piperonal directly activated Adcy by decreasing the Km
for its substrate (ATP) in plasma membranes prepared from the WAT of mice.
Furthermore, piperonal-induced inhibition of adipocyte differentiation and
elevation of Adcy and PKA activities in 3T3-L1 cells were abrogated by an Adcy
inhibitor. CONCLUSION: The anti-adipogenic effect of piperonal in mice fed the
high-fat diet appears to be associated with increased Adcy-PKA signaling in WAT.
PMID- 28699237
TI - Evaluation of visual and computer-based CT analysis for the identification of
functional patterns of obstruction and restriction in hypersensitivity
pneumonitis.
AB - BACKGROUND AND OBJECTIVE: To determine whether computer-based quantification
(CALIPER software) is superior to visual computed tomography (CT) scoring in the
identification of CT patterns indicative of restrictive and obstructive
functional indices in hypersensitivity pneumonitis (HP). METHODS: A total of 135
consecutive HP patients had CT parenchymal patterns evaluated quantitatively by
both visual scoring and CALIPER. Results were evaluated against: forced vital
capacity (FVC), total lung capacity (TLC), diffusing capacity for carbon monoxide
(DLCO ) and a composite physiological index (CPI) to identify which CT scoring
method better correlated with functional indices. RESULTS: CALIPER-derived scores
of total interstitial lung disease extent correlated more strongly than visual
scores: FVC (CALIPER R = 0.73, visual R = 0.51); DLCO (CALIPER R = 0.61, visual R
= 0.48); and CPI (CALIPER R = 0.70, visual R = 0.55). The CT variable that
correlated most strongly with restrictive functional indices was CALIPER
pulmonary vessel volume (PVV): FVC R = 0.75, DLCO R = 0.68 and CPI R = 0.76.
Ground-glass opacity quantified by CALIPER alone demonstrated strong associations
with restrictive functional indices: CALIPER FVC R = 0.65; DLCO R = 0.59; CPI R =
0.64; and visual = not significant. Decreased attenuation lung quantified by
CALIPER was a better morphological measure of obstructive lung disease than
equivalent visual scores as judged by relationships with TLC (CALIPER R = 0.63
and visual R = 0.12). All results were maintained on multivariate analysis.
CONCLUSION: CALIPER improved on visual scoring in HP as judged by restrictive and
obstructive functional correlations. Decreased attenuation regions of the lung
quantified by CALIPER demonstrated better linkages to obstructive lung physiology
than visually quantified CT scores. A novel CALIPER variable, the PVV,
demonstrated the strongest linkages with restrictive functional indices and could
represent a new automated index of disease severity in HP.
PMID- 28699238
TI - Increased matrix stiffness promotes tumor progression of residual hepatocellular
carcinoma after insufficient heat treatment.
AB - Aggravated behaviors of hepatocellular carcinoma (HCC) will occur after
inadequate thermal ablation. However, its underlying mechanisms are not fully
understood. Here, we assessed whether the increased matrix stiffness after
thermal ablation could promote the progression of residual HCC. Heat-treated
residual HCC cells were cultured on tailorable 3D gel with different matrix
stiffness, simulating the changed physical environment after thermal ablation,
and then the mechanical alterations of matrix stiffness on cell phenotypes were
explored. Increased stiffness was found to significantly promote the
proliferation of the heat-treated residual HCC cells when the cells were cultured
on stiffer versus soft supports, which was associated with stiffness-dependent
regulation of ERK phosphorylation. Heat-exposed HCC cells cultured on stiffer
supports showed enhanced motility. More importantly, vitamin K1 reduced stiffness
dependent residual HCC cell proliferation by inhibiting ERK phosphorylation and
suppressed the in vivo tumor growth, which was further enhanced by combining with
sorafenib. Increased matrix stiffness promotes the progression of heat-treated
residual HCC cells, proposing a new mechanism of an altered biomechanical
environment after thermal ablation accelerates HCC development. Vitamin K1 plus
sorafenib can reverse this protumor effect.
PMID- 28699239
TI - Analysis of individual cells identifies cell-to-cell variability following
induction of cellular senescence.
AB - Senescent cells play important roles in both physiological and pathological
processes, including cancer and aging. In all cases, however, senescent cells
comprise only a small fraction of tissues. Senescent phenotypes have been studied
largely in relatively homogeneous populations of cultured cells. In vivo,
senescent cells are generally identified by a small number of markers, but
whether and how these markers vary among individual cells is unknown. We
therefore utilized a combination of single-cell isolation and a nanofluidic PCR
platform to determine the contributions of individual cells to the overall gene
expression profile of senescent human fibroblast populations. Individual
senescent cells were surprisingly heterogeneous in their gene expression
signatures. This cell-to-cell variability resulted in a loss of correlation among
the expression of several senescence-associated genes. Many genes encoding
senescence-associated secretory phenotype (SASP) factors, a major contributor to
the effects of senescent cells in vivo, showed marked variability with a subset
of highly induced genes accounting for the increases observed at the population
level. Inflammatory genes in clustered genomic loci showed a greater correlation
with senescence compared to nonclustered loci, suggesting that these genes are
coregulated by genomic location. Together, these data offer new insights into how
genes are regulated in senescent cells and suggest that single markers are
inadequate to identify senescent cells in vivo.
PMID- 28699240
TI - The prevalence of peripheral intravenous cannulae and pattern of use: A point
prevalence in a private hospital setting.
AB - AIMS AND OBJECTIVES: To determine the prevalence and pattern of use of peripheral
intravenous cannulae in hospital wards. BACKGROUND: Peripheral intravenous
cannulae are commonly used in acute health care to directly access the
bloodstream for the administration of medications, intravenous fluids and blood
products. Peripheral intravenous cannulae are associated with multiple adverse
events including hospital-acquired bloodstream infection, thrombophlebitis and
pain/discomfort. Administration of intravenous fluids is associated with impaired
mobility and nocturia which may increase falls risk in the older people. DESIGN:
Observational, point prevalence study. METHODS: Three private hospitals
comprising a total of 1,230 beds participated in the study. Nurses recorded the
presence of a peripheral intravenous cannulae, duration of insertion, state of
the dressing and whether the peripheral intravenous cannulae was accessed in the
previous 24 hr and for what purpose. Nurses were also asked whether they would
replace the peripheral intravenous cannulae should it fail. RESULTS:
Approximately one-quarter of patients had a peripheral intravenous cannulae, the
majority of which had been present for <24 hr. The major use of the peripheral
intravenous cannulae was antibiotic administration. Administration of intravenous
fluids occurred in the presence of normal oral fluid intake. Nurses would not
replace one-third of peripheral intravenous cannulae in the event of failure. A
majority of patients were at increased falls risk, and one-third of these were
receiving intravenous fluids. CONCLUSIONS: There is room for improvement in the
utilisation of peripheral intravenous cannulae, particularly in removal and
associated use of intravenous fluids. Alternative strategies for medication
administration and timely switch to the oral route may reduce the risks
associated with intravenous fluids. RELEVANCE TO CLINICAL PRACTICE: Vigilance is
required in the use of peripheral intravenous cannulae. Consider transition of
medication administration to oral intake where possible to minimise risks
associated with the use of invasive devices and increased fluid intake.
PMID- 28699242
TI - Plant lignans inhibit growth trichothecene biosynthesis in Fusarium graminearum.
PMID- 28699243
TI - Comparison between electromagnetic transponders and radiographic imaging for
prostate localization: A pelvic phantom study with rotations and translations.
AB - The aim of this study was to evaluate the differences in target localization
between Calypso(r) , kV orthogonal imaging and cone-beam computed tomography
(CBCT) for combined translations and rotations of an anthropomorphic pelvic
phantom. The phantom was localized using all three systems in 50 different
positions, with applied translational and rotational offsets randomly sampled
from representative normal distributions of prostate motion. Lin's concordance
correlation coefficient (rhoc) and 95% confidence intervals were calculated to
assess the agreement between the localization systems. Mean differences and
difference vectors between the three systems were also calculated. Agreement
between systems for lateral, vertical, and longitudinal translations was
excellent, with rhoc values of greater than 0.98 between all three systems in all
axes. There was excellent agreement between the systems for rotations around the
lateral axis (pitch) (rhoc > 0.99), and around the vertical axis (yaw) (rhoc >
0.97). However, somewhat poorer agreement for rotations around the longitudinal
axis (roll) was observed, with the lowest correlation observed between Calypso
and kV orthogonal imaging (rhoc = 0.895). Mean differences between the phantom
position reported by Calypso and the radiographic systems were less than 1 mm and
1 degrees for all translations and rotations. The results for translations are
consistent with the publications of previous authors. There is no comparable
published data for rotations. While there is lower correlation between the three
systems for roll than for the other angles, the mean differences in reported
rotations are not clinically significant.
PMID- 28699241
TI - Calcium dependence of spontaneous neurotransmitter release.
AB - Spontaneous release of neurotransmitters is regulated by extracellular [Ca2+ ]
and intracellular [Ca2+ ]. Curiously, some of the mechanisms of Ca2+ signaling at
central synapses are different at excitatory and inhibitory synapses. While the
stochastic activity of voltage-activated Ca2+ channels triggers a majority of
spontaneous release at inhibitory synapses, this is not the case at excitatory
nerve terminals. Ca2+ release from intracellular stores regulates spontaneous
release at excitatory and inhibitory terminals, as do agonists of the Ca2+
sensing receptor. Molecular machinery triggering spontaneous vesicle fusion may
differ from that underlying evoked release and may be one of the sources of
heterogeneity in release mechanisms.
PMID- 28699244
TI - Biophysical characterization of layer-by-layer synthesis of aptamer-drug
microparticles for enhanced cell targeting.
AB - Targeted delivery of drug molecules to specific cells in mammalian systems
demonstrates a great potential to enhance the efficacy of current pharmaceutical
therapies. Conventional strategies for pharmaceutical delivery are often
associated with poor therapeutic indices and high systemic cytotoxicity, and this
result in poor disease suppression, low surviving rates, and potential
contraindication of drug formulation. The emergence of aptamers has elicited new
research interests into enhanced targeted drug delivery due to their unique
characteristics as targeting elements. Aptamers can be engineered to bind to
their cognate cellular targets with high affinity and specificity, and this is
important to navigate active drug molecules and deliver sufficient dosage to
targeted malignant cells. However, the targeting performance of aptamers can be
impacted by several factors including endonuclease-mediated degradation, rapid
renal filtration, biochemical complexation, and cell membrane electrostatic
repulsion. This has subsequently led to the development of smart aptamer
immobilized biopolymer systems as delivery vehicles for controlled and sustained
drug release to specific cells at effective therapeutic dosage and minimal
systemic cytotoxicity. This article reports the synthesis and in vitro
characterization of a novel multi-layer co-polymeric targeted drug delivery
system based on drug-loaded PLGA-Aptamer-PEI (DPAP) formulation with a stage-wise
delivery mechanism. A thrombin-specific DNA aptamer was used to develop the DPAP
system while Bovine Serum Albumin (BSA) was used as a biopharmaceutical drug in
the synthesis process by ultrasonication. Biophysical characterization of the
DPAP system showed a spherical shaped particulate formulation with a unimodal
particle size distribution of average size ~0.685 um and a zeta potential of
+0.82 mV. The DPAP formulation showed a high encapsulation efficiency of 89.4 +/-
3.6%, a loading capacity of 17.89 +/- 0.72 mg BSA protein/100 mg PLGA polymeric
particles, low cytotoxicity and a controlled drug release characteristics in 43
days. The results demonstrate a great promise in the development of DPAP
formulation for enhanced in vivo cell targeting. (c) 2017 American Institute of
Chemical Engineers Biotechnol. Prog., 34:249-261, 2018.
PMID- 28699245
TI - Effects of intranasally dosed posaconazole on fungal load and biomarkers in
Aspergillus fumigatus infected immunocompromised mice.
AB - Although anti-fungal triazoles are dosed orally or systemically for Aspergillus
fumigatus infection, systemic adverse events and limited exposure of the lung
cavity would make a topical treatment for the lung an attractive option. In this
study, we examined the effects of intranasally dosed posaconazole on survival
rates and biomarkers in A. fumigatus (itraconazole susceptible: ATCC13073 [Af];
or resistant: NCPF7100 [AfR]) infected, temporarily neutropenic A/J mice. Once
daily treatment produced a dose-dependent improvement of survival of Af-infected
mice (ED50 : 0.019 mg/mouse [approx. 0.755 mg/kg, in]), similar to its potency
(ED50 : 0.775 mg/kg, po) after once daily oral dosing. For AfR infection, either
intranasal or oral posaconazole was largely ineffective on survival, although the
highest dose of intranasal treatment (0.35 mg/mouse) achieved 75% survival rate.
Early intervention (treated on days 0, 1, 2 and 3 postinfection) and late
intervention (treated on days 1, 2 and 3) with intranasal posaconazole (0.014
0.35 mg/mouse) demonstrated potent inhibition of lung fungal load and
galactomannan levels in both bronchoalveolar lavage fluid (BALF) and serum as
well as inflammatory cells, IFN-gamma, IL-17 and malondialdehyde (MDA) in BALF.
Thus, posaconazole when dosed intranasally once daily showed an improvement of
survival equivalent to or better than oral treatment, and produced potent
inhibition of fungal load and biomarkers.
PMID- 28699246
TI - A potential pitfall in studies of biological shape: Does size matter?
AB - The number of published studies using geometric morphometrics (GM) for analysing
biological shape has increased steadily since the beginning of the 1990s,
covering multiple research areas such as ecology, evolution, development,
taxonomy and palaeontology. Unfortunately, we have observed that many published
studies using GM do not evaluate the potential allometric effects of size on
shape, which normally require consideration or assessment. This might lead to
misinterpretations and flawed conclusions in certain cases, especially when size
effects explain a large part of the shape variation. We assessed, for the first
time and in a systematic manner, how often published studies that have applied GM
consider the potential effects of allometry on shape. We reviewed the 300 most
recent published papers that used GM for studying biological shape. We also
estimated how much of the shape variation was explained by allometric effects in
the reviewed papers. More than one-third (38%) of the reviewed studies did not
consider the allometric component of shape variation. In studies where the
allometric component was taken into account, it was significant in 88% of the
cases, explaining up to 87.3% of total shape variation. We believe that one
reason that may cause the observed results is a misunderstanding of the process
that superimposes landmark configurations, i.e. the Generalized Procrustes
Analysis, which removes isometric effects of size on shape, but not allometric
effects. Allometry can be a crucial component of shape variation. We urge authors
to address, and report, size effects in studies of biological shape. However, we
do not propose to always remove size effects, but rather to evaluate the research
question with and without the allometric component of shape variation. This
approach can certainly provide a thorough understanding of how much size
contributes to the observed shaped variation.
PMID- 28699247
TI - Advance MR imaging in sports-related concussion and mild traumatic brain injury -
ready for clinical use? (Commentary on Tremblay et al. 2017).
PMID- 28699248
TI - Phenotypical characteristics of postpartum psychosis: A clinical cohort study.
AB - OBJECTIVES: Postpartum psychosis (PP) is known for its clear onset but its
phenotype has never been clearly described in a cohort. The aim of this study was
to describe PP symptomatology, and to identify subgroups of patients based on
symptom profiles. METHODS: We prospectively assessed a wide range of symptoms in
cases of PP in a cohort of women (N=130) admitted to the Mother-Baby inpatient
unit. Using a person-centered analytic approach, we distinguished mutually
exclusive subgroups of women. Subgroups were related to demographic and clinical
characteristics. RESULTS: The most prevalent symptoms of PP were irritability
(73%), abnormal thought content (72%), and anxiety (71%). Suicidal and
infanticidal ideation was present in 19% and 8% of patients, respectively.
Delusions and hallucinations often had a negative content. Latent class analysis
revealed three symptom profiles, a manic (34%), depressive (41%) and atypical
(25%) profile, respectively. The manic profile is characterized by manic symptoms
and agitation, the depressive profile by depressive and anxiety symptoms, and the
atypical profile by disturbance of consciousness and disorientation. In women
with a depressive profile, treatment was started 2 weeks later (P=.049), and more
often voluntarily, than in manic and atypical women (P=.037). CONCLUSIONS: We
distinguished subgroups of PP patients with a manic, depressive, and atypical
profile. Disturbance of consciousness, disorientation, and
depersonalization/derealization were less prevalent than previously suggested in
the literature. Instead, the depressive profile was the most prevalent, but the
depressive profile can easily remain undetected, which could lead to treatment
delay and risk of suicide/infanticide. Within the manic profile, irritability was
highly prevalent and occurred more often than elevated mood.
PMID- 28699249
TI - Targeted next generation sequencing identifies a novel beta-spectrin gene
mutation A2059P in two Omani children with hereditary pyropoikilocytosis.
PMID- 28699250
TI - The pharyngeal contractile integral is a useful indicator of pharyngeal
swallowing impairment.
AB - BACKGROUND: A limitation to the expanded use of high-resolution pharyngeal
manometry (HRPM) in clinical practice is the lack of useful pharyngeal parameters
that are easy to interpret, generalizable between patients, and do not require
specialized software. In this study, we sought to test the relationship between
the pharyngeal contractile integral (PhCI) with videofluoroscopic abnormalities
as assessed with the Modified Barium Swallow Impairment Profile(c) TM. METHODS:
Adult dysphagic patients were recruited to undergo simultaneous HRPM and
videofluoroscopy during a standardized swallowing protocol. KEY RESULTS: Thirty
six patients were included in the study. The mean PhCI was 247 mm Hg.cm.s (range
2-488 mm Hg.cm.s). The lower pharyngeal total (PT) group (N=20; mean PT=3.9) had
a mean PhCI of 299 mm Hg.cm.s, while the higher PT group (N=16; mean PT=12.7) had
a mean PhCI score of 188 mm Hg.cm.s (P=.01). There was also a significant
negative correlation between normalized PhCI to PT scores (r=-.47; P=.004).
Patients with higher PhCIs exhibited less severe penetration-aspiration scores on
thin liquids (1.44 vs 3.78; P=.03) and all consistencies combined (1.21 vs 1.99;
P=.03). CONCLUSIONS & INFERENCES: The PhCI is a useful indicator of the presence
of pharyngeal swallowing impairment and is technically simple to calculate with
currently available software programs. Advancement of software is necessary to
refine the clinical value of this parameter. High-resolution pharyngeal manometry
has the potential to be a valuable adjunct procedure for the evaluation and
treatment of dysphagic individuals.
PMID- 28699251
TI - Antituberculotic activity of actinobacteria isolated from the rare habitats.
AB - : A distinctive screening procedure resulted in the isolation and identification
of antituberculotic actinobacteria. In this course, a total of 125 actinobacteria
were isolated from various soil samples from untapped areas in Northwestern
Himalayas, India. The antibacterial screening showed that 26 isolates inhibited
the growth of at least one of the tested bacterial pathogens including
Staphylococcus aureus (ATCC 25923), Staphylococcus epidermidis (ATCC 12228),
Bacillus subtilis (ATCC 11774), Micrococcus luteus (ATCC 10240), Escherichia coli
(10536), Pseudomonas aeruginosa (ATCC 10145) and Klebsiella pneumonia (ATCC BAA
2146). The production media was optimized for the active strains by estimation of
their extract value by the quantification of the ethyl acetate extract. The
screening of fermentation products from the selected 26 bioactive isolates
revealed that 10 strains have metabolites antagonistic against the standard H37Rv
strain of Mycobacterium tuberculosis. The characterization by 16S rRNA gene
sequencing and phylogenetic analysis demonstrated the diverse nature of these
antituberculosis strains. The secondary metabolites of potent, rare strain,
Lentzea violacea AS08 exhibited promising antituberculosis activity with minimal
inhibitory concentration (MIC) of 3.9 MUg ml-1 . The metabolites identified by
gas chromatography-mass spectrometry (GC-MS) included, Phenol, 2,5-bis (1, 1
dimethylethyl), n-Hexadecanoic acid, Hexadecanoic acid methyl-ester, Hexadecanoic
acid ethyl-ester and, 9,12-Octadecadienoyl chloride(Z,Z) are biologically
significant molecules. SIGNIFICANCE AND IMPACT OF STUDY: The study presents the
isolation of rare actinobacteria from untapped sites in the Northwestern
Himalayas and their in vitro potential against Mycobacterium tuberculosis for
their metabolites. The study revealed that exploring the untapped natural sources
as one of the resourceful approaches for the discovery of new natural products.
This study also provided strong evidence for the ability of rare and potent
actinobacterial strains to produce bioactive compounds with antagonistic activity
and these metabolites can be studied for inhibitory potential.
PMID- 28699252
TI - Mesenchymal Stromal Cell-Derived Interleukin-6 Promotes Epithelial-Mesenchymal
Transition and Acquisition of Epithelial Stem-Like Cell Properties in
Ameloblastoma Epithelial Cells.
AB - Epithelial-mesenchymal transition (EMT), a biological process associated with
cancer stem-like or cancer-initiating cell formation, contributes to the
invasiveness, metastasis, drug resistance, and recurrence of the malignant
tumors; it remains to be determined whether similar processes contribute to the
pathogenesis and progression of ameloblastoma (AM), a benign but locally invasive
odontogenic neoplasm. Here, we demonstrated that EMT- and stem cell-related genes
were expressed in the epithelial islands of the most common histologic variant
subtype, the follicular AM. Our results revealed elevated interleukin (IL)-6
signals that were differentially expressed in the stromal compartment of the
follicular AM. To explore the stromal effect on tumor pathogenesis, we isolated
and characterized both mesenchymal stromal cells (AM-MSCs) and epithelial cells
(AM-EpiCs) from follicular AM and demonstrated that, in in vitro culture, AM-MSCs
secreted a significantly higher level of IL-6 as compared to the counterpart AM
EpiCs. Furthermore, both in vitro and in vivo studies revealed that exogenous and
AM-MSC-derived IL-6 induced the expression of EMT- and stem cell-related genes in
AM-EpiCs, whereas such effects were significantly abrogated either by a specific
inhibitor of STAT3 or ERK1/2, or by knockdown of Slug gene expression. These
findings suggest that AM-MSC-derived IL-6 promotes tumor-stem like cell formation
by inducing EMT process in AM-EpiCs through STAT3 and ERK1/2-mediated signaling
pathways, implying a role in the etiology and progression of the benign but
locally invasive neoplasm. Stem Cells 2017;35:2083-2094.
PMID- 28699253
TI - On the clinical utility and empirical verification of nontraditional
interventions: Nidotherapy as exemplar.
PMID- 28699254
TI - E-cadherin expression increases cell proliferation by regulating energy
metabolism through nuclear factor-kappaB in AGS cells.
AB - beta-Catenin is a central player in Wnt signaling, and activation of Wnt
signaling is associated with cancer development. E-cadherin in complex with beta
catenin mediates cell-cell adhesion, which suppresses beta-catenin-dependent Wnt
signaling. Recently, a tumor-suppressive role for E-cadherin has been
reconsidered, as re-expression of E-cadherin was reported to enhance the
metastatic potential of malignant tumors. To explore the role of E-cadherin, we
established an E-cadherin-expressing cell line, EC96, from AGS cells that
featured undetectable E-cadherin expression and a high level of Wnt signaling. In
EC96 cells, E-cadherin re-expression enhanced cell proliferation, although Wnt
signaling activity was reduced. Subsequent analysis revealed that nuclear factor
kappaB (NF-kappaB) activation and consequent c-myc expression might be involved
in E-cadherin expression-mediated cell proliferation. To facilitate rapid
proliferation, EC96 cells enhance glucose uptake and produce ATP using both
mitochondria oxidative phosphorylation and glycolysis, whereas AGS cells use
these mechanisms less efficiently. These events appeared to be mediated by NF
kappaB activation. Therefore, E-cadherin re-expression and subsequent induction
of NF-kappaB signaling likely enhance energy production and cell proliferation.
PMID- 28699255
TI - Internal and external validity of Chen et al.'s nursing-sensitive quality
indicators for the neonatal intensive care unit.
PMID- 28699256
TI - Long-term analysis of phase II studies of single-agent lenalidomide in
relapsed/refractory mantle cell lymphoma.
AB - Mantle cell lymphoma (MCL) is a type of non-Hodgkin lymphoma (NHL) with
aggressive disease characteristics resulting in multiple relapses after initial
treatment. Lenalidomide is an immunomodulatory agent approved in the US for
patients with relapsed/refractory MCL following bortezomib based on results from
3 multicenter phase II studies (2 including relapsed/refractory aggressive NHL
and 1 focusing on MCL post-bortezomib). The purpose of this report is to provide
longer follow-up on the MCL-001 study (follow-ups were 6.8 [NHL-002], 7.6 [NHL
003], and 52.2 [MCL-001] months). The 206 relapsed MCL patients treated with
single-agent lenalidomide (25 mg/day PO, days 1 to 21 every 28-days) had a median
age of 67 years (63% >=65 years), 91% with stage III/IV disease, and 50% with >=4
previous treatment regimens. With a median follow-up of X, the combined best
overall response rate (ORR) was 33% (including 11% with complete remission
[CR]/CR unconfirmed CRu). Lenalidomide produced rapid and durable responses with
a median time to response of 2.2 months and median duration of response (DOR) of
16.6 months (95% CI: 11.1%-29.8%). The safety profile was consistent and
manageable; myelosuppression was the most common adverse event (AE). Overall,
single-agent lenalidomide showed consistent efficacy and safety in multiple phase
II studies of heavily pretreated patients with relapsed/refractory MCL, including
those previously treated with bortezomib.
PMID- 28699257
TI - Effects of ochratoxin A on ER stress, MAPK signaling pathway and autophagy of
kidney and spleen in pigs.
AB - Ochratoxin A (OTA), a worldwide mycotoxin found in food and feeds, is a potent
nephrotoxin and immunotoxin in animals and humans. This research was conducted to
evaluate whether endoplasmic reticulum (ER) stress, MAPK signaling pathway and
autophagy were induced by OTA in kidney and spleen of pigs. Twenty-seven
crossbred pigs randomly allocated to 3 groups were fed for 42 days ad libitum a
basal diet without (Con group, 0.00 MUg OTA/kg) and with supplementation of OTA
at 400 (OTA-L group) and 800 MUg/kg (OTA-H group). From each group, 6 pigs were
randomly selected for blood collection on days 0, 21, and 42 and 3 pigs were
randomly selected for tissue collection on day 42. The results showed that OTA at
400 and 800 MUg/kg diets significantly increased OTA concentrations in serum and
kidney and spleen induced the histopathological lesions of kidney and spleen,
decreased TCR-stimulated T lymphocyte viabilities and IL-2 concentration,
increased TNF-alpha concentration, and decreased T-AOC levels. OTA increased
glucose regulated protein 78, p38, and ERK1/2 phosphorylation, and LC3 II and
Atg5 protein expression in kidney and spleen of pigs. These results provide new
insights into the relationship between OTA and ER stress, p38 and ERK1/2 MAPK
signaling pathway and autophagy in pigs.
PMID- 28699258
TI - Cytotoxic peptides with insulin-releasing activities from skin secretions of the
Italian stream frog Rana italica (Ranidae).
AB - Peptidomic analysis of norepinephrine-stimulated skin secretions from Italian
stream frog Rana italica led to the purification and characterization of two host
defense peptides differing by a single amino acid residue belonging to the
brevinin-1 family (brevinin-1ITa and -1ITb), a peptide belonging to the temporin
family (temporin-ITa) and a component identified as prokineticin Bv8. The
secretions contained relatively high concentrations of the methionine-sulphoxide
forms of brevinin-1ITa and -1ITb suggesting that these peptides may have a role
as antioxidants in the skin of this montane frog. Brevinin-1ITa
(IVPFLLGMVPKLVCLITKKC) displayed potent cytotoxicity against non-small cell lung
adenocarcinoma A549 cells (LC50 = 18 MUM), breast adenocarcinoma MDA-MB-231
cells (LC50 = 8 MUM) and colorectal adenocarcinoma HT-29 cells (LC50 = 18 MUM),
but the peptide was also strongly hemolytic against mouse erythrocytes (LC50 = 7
MUM). Temporin-ITa (VFLGAIAQALTSLLGKL.NH2 ) was between three and fivefold less
potent against these cells. Brevinin-1ITa inhibited growth of both Gram-positive
Staphylococcus epidermidis and Gram-negative Escherichia coli as well as a strain
of the opportunist yeast pathogen Candida parapsilosis, whereas temporin-ITa was
active only against S. epidermidis and C. parapsilosis. Both peptides stimulated
the release of insulin from BRIN-BD11 clonal beta-cells at concentrations >=1 nM,
but brevinin-1ITa was cytotoxic to the cells at concentrations >=3 MUM. Copyright
(c) 2017 European Peptide Society and John Wiley & Sons, Ltd.
PMID- 28699259
TI - Increasing temperature cuts back crop yields in Hungary over the last 90 years.
AB - The transformation of climatic regime has an undeniable impact on plant
production, but we rarely have long enough date series to examine the unfolding
of such effects. The clarification of the relationship between crop plants and
climate has a near-immediate importance due to the impending human-made global
change. This study investigated the relationship between temperature,
precipitation, drought intensity and the yields of four major cereals in Hungary
between 1921 and 2010. The analysis of 30-year segments indicated a monotonously
increasing negative impact of temperature on crop yields. A 1 degrees C
temperature increase reduced the yield of the four main cereals by 9.6%-14.8% in
1981-2010, which revealed the vulnerability of Eastern European crop farming to
recent climate change. Climate accounted for 17%-39% of yield variability over
the past 90 years, but this figure reached 33%-67% between 1981 and 2010. Our
analysis supports the claim that the mid-20th century green revolution improved
yields "at the mercy of the weather": during this period, the impact of
increasing fertilization and mechanisation coincided with climatic conditions
that were more favourable than today. Crop yields in Eastern Europe have been
stagnating or decreasing since the mid-1980s. Although usually attributed to the
large socio-economic changes sweeping the region, our analysis indicates that a
warming climate is at least partially responsible for this trend. Such a robust
impact of increasing temperatures on crop yields also constitutes an obvious
warning for this core grain-growing region of the world.
PMID- 28699260
TI - Australian recommendations for EGFR T790M testing in advanced non-small cell lung
cancer.
AB - First-generation epidermal growth factor receptor (EGFR) tyrosine kinase
inhibitors (TKIs) are used as first-line therapy in patients with non-small cell
lung cancer (NSCLC) harboring a sensitizing mutation in the EGFR gene.
Unfortunately, resistance to these therapies often occurs within 10 months of
commencing treatment and is mostly commonly due to the development of the EGFR
T790M mutation. Treatment with the third-generation EGFR TKI, osimertinib can
prolong progression free survival in patients with the T790M mutation, so it is
important to determine the resistance mechanism in order to plan ongoing
therapeutic strategies. Here we review the evidence and make recommendations for
the timing of T790M mutation testing, the most appropriate specimens to test and
the available testing methods in patients progressing during treatment with first
line EGFR TKIs for NSCLC.
PMID- 28699261
TI - NPQ(T) : a chlorophyll fluorescence parameter for rapid estimation and imaging of
non-photochemical quenching of excitons in photosystem-II-associated antenna
complexes.
AB - In photosynthesis, light energy is absorbed by light-harvesting complexes and
used to drive photochemistry. However, a fraction of absorbed light is lost to
non-photochemical quenching (NPQ) that reflects several important photosynthetic
processes to dissipate excess energy. Currently, estimates of NPQ and its
individual components (qE , qI , qZ and qT ) are measured from pulse-amplitude
modulation (PAM) measurements of chlorophyll fluorescence yield and require
measurements of the maximal yield of fluorescence in fully dark-adapted material
(Fm ), when NPQ is assumed to be negligible. Unfortunately, this approach
requires extensive dark acclimation, often precluding widespread or high
throughput use, particularly under field conditions or in imaging applications,
while introducing artefacts when Fm is measured in the presence of residual
photodamaged centres. To address these limitations, we derived and characterized
a new set of parameters, NPQ(T) , and its components that can be (1) measured in
a few seconds, allowing for high-throughput and field applications; (2) does not
require full relaxation of quenching processes and thus can be applied to
photoinhibited materials; (3) can distinguish between NPQ and chloroplast
movements; and (4) can be used to image NPQ in plants with large leaf movements.
We discuss the applications benefits and caveats of both approaches.
PMID- 28699262
TI - Recurrent myocardial infarction in a 47-year-old woman with a mechanical mitral
valve prosthesis: Atherosclerosis, embolism, or spasm?
AB - We present a case of a 47-year-old woman with a mechanical mitral valve
prosthesis and recurrent myocardial infarction. The most common etiology of
spontaneous myocardial infarction is an acute coronary syndrome caused by rupture
or erosion of an atherosclerotic plaque. However, the differential diagnosis in
the patient described below also included infarction due to embolization or
coronary spasm. It can be challenging to discriminate between the different
causes of myocardial infarction based on interpretation of symptoms, physical
examination, laboratory tests, and electrocardiography alone. This report
illustrates the value of coronary angiography with invasive coronary spasm
provocation testing using intracoronary acetylcholine to identify the etiology of
her recurrent myocardial infarctions.
PMID- 28699263
TI - Predictors of Early Continence after Robot-assisted Radical Prostatectomy.
AB - OBJECTIVE: Our objective was to investigate predictors of early continence
outcome after robot-assisted radical prostatectomy (RARP). METHODS: Clinical
records were prospectively collected in 272 patients who underwent RARP. Clinical
parameters, continence rates, and time to achieve continence were investigated
and analyzed. Recovery of continence was defined as achieving complete continence
(pad-free). RESULTS: In the univariate analysis, young age (<=67 years) and low
pT stage (<=pT2) were significantly associated with continence achieved within 2
weeks after RARP (P = 0.0343 and P = 0.0406, respectively). Low prostate weight
was the only factor associated with recovery of continence within 1 month (P =
0.0461). Multivariate analysis revealed that young age (<=67 years) and low pT
stage (<=pT2) were statistically significant predictors of continence within 2
weeks after RARP (P = 0.040 and P = 0.015, respectively). CONCLUSION: Young age
and low pT stage were independent predictors of early continence.
PMID- 28699264
TI - POEMS syndrome: An elusive diagnosis.
PMID- 28699265
TI - Effects of harsh parenting and positive parenting practices on youth aggressive
behavior: The moderating role of early pubertal timing.
AB - Prior research indicates that early pubertal timing is associated with aggressive
behavior, particularly in the context of adversity as postulated in the
contextual amplification hypothesis. However, few studies have examined harsh
parenting as the context for the effect of early pubertal timing. Even fewer
studies have tested the interactive effect of early pubertal timing and positive
parenting on aggressive behavior. In this study, we tested the proposition that
early pubertal timing, contrary to the general conception of it as a
vulnerability, indexed susceptibility, and thus early maturing individuals were
affected more by their environment in a "for better and for worse" manner. The
sample consisted of 411 community-recruited youth aged 11-12 years (51% boys, 80%
African Americans). Participants reported Tanner Stages of pubertal development,
aggressive behavior and harsh parenting practice of their parents. Puberty scores
were standardized with groups of the same age, sex, and ethnicity, and those that
scored the top one-third were defined as early maturing individuals. Parents
reported youth's aggressive behavior and their parenting practices towards the
youth, including harsh parenting and positive parenting. Early pubertal timing
significantly moderated the relationship between harsh/positive parenting and
aggressive behavior. Specifically, harsh parenting was positively associated with
aggressive behavior to a larger degree among early maturing individuals than
among on-time/late-maturing individuals. Positive parenting was inversely
associated with aggressive behavior but only among early maturing individuals.
This study is the first to document support for early pubertal timing as
susceptibility to the environmental influences in relation to aggressive
behavior. Theoretical and intervention implications are discussed.
PMID- 28699266
TI - Can we make genomic selection 100% accurate?
PMID- 28699267
TI - Lucerastat, an Iminosugar for Substrate Reduction Therapy: Tolerability,
Pharmacodynamics, and Pharmacokinetics in Patients With Fabry Disease on Enzyme
Replacement.
AB - Lucerastat is a glucosylceramide synthase inhibitor aimed at reducing production
of glycosphingolipids (GSLs), including those accumulating in Fabry disease. The
safety, tolerability, pharmacodynamics, and pharmacokinetics of oral lucerastat
were evaluated in an exploratory study in patients with Fabry disease. In this
single-center, open-label, randomized study, 10 patients received lucerastat
1,000 mg b.i.d. for 12 weeks in addition to enzyme replacement therapy (ERT; the
lucerastat group). Four patients with Fabry disease received ERT only. Eight
patients reported 17 adverse events (AEs) in the lucerastat group. No clinically
relevant safety abnormalities were observed. The mean (SD) levels of the plasma
GSLs, glucosylceramide, lactosylceramide, and globotriaosylceramide, were
significantly decreased from baseline in the lucerastat group (-49.0% (16.5%),
32.7% (13.0%), and -55.0% (10.4%), respectively). Lucerastat 1,000 mg b.i.d. was
well tolerated in patients with Fabry disease over 12 weeks. A marked decrease in
plasma GSLs was observed, suggesting clinical potential for lucerastat in
patients with Fabry disease.
PMID- 28699268
TI - An integrative review of supports, facilitators and barriers to patient-centred
nursing in the intensive care unit.
AB - AIMS AND OBJECTIVES: To systematically review the literature describing factors
perceived by nurses as impacting the provision of patient-centred nursing in the
intensive care unit. BACKGROUND: Patient-centred nursing in critical care differs
from other healthcare areas, and the aggressive curative environment of the ICU
has potential to compromise some of its elements. Understanding critical care,
nurses' perceptions of promoting and deterrent factors may inform development of
strategies to support effective patient-centred nursing and job satisfaction in
this workforce. DESIGN: An integrative literature review. REVIEW METHOD:
Whittemore and Knafl's method was used with "best-fit" framework synthesis.
CINAHL, PsycINFO, Medline and EMBASE were searched for 2000-2016 literature using
search terms drawn from the ICU patient-centred framework. RESULTS: In total,
3,079 papers were identified, with 23 retained after applying eligibility
criteria. Five themes were identified: Nurse identity; Organisation;
Communication; Relationships; and Ideology of ICU. Almost every theme and related
categories referred to factors acting as barriers to patient-centred nursing in
the ICU; only four referred to supports/facilitators. Findings showed that
provision of patient-centred nursing may be compromised by some factors of the
critical care environment, and illustrate the challenges and complexity of
providing effective patient-centred nursing in this environment. CONCLUSION:
Findings should be applied to address barriers and to enhance facilitators of
effective patient-centred nursing in critical care. The emotional and physical
demands of critical care nursing are major considerations; supporting these
nurses to fulfil their challenging role may empower them in their professional
quality of life and provide a basis for workforce retention as well as delivery
of effective patient-centred nursing. RELEVANCE TO CLINICAL PRACTICE: Measures to
enhance patient-centred nursing could promote critical care nurses' job
satisfaction and workforce retention, and be applied more broadly and
collaboratively to promote multidisciplinary patient-centred care.
PMID- 28699269
TI - Determinants of short and long term outcomes in patients undergoing immediate
breast reconstruction following neoadjuvant chemotherapy.
AB - BACKGROUND: We evaluated oncologic outcomes and complications of skin-sparing
mastectomy (SSM) and nipple-sparing mastectomy (NSM) with immediate
reconstruction (IR) after neoadjuvant chemotherapy (NAC) in patients with early
stage and locally advanced breast cancer (BC). METHODS: BC patients from 2000 to
2014 treated with NAC followed by SSM/NSM and IR were reviewed. Patient
demographics, tumor characteristics, NAC response, complications, and recurrence
were analyzed. RESULTS: Two hundred sixty-nine patients with 280 BCs were treated
with NAC followed by SSM (94%) or NSM (6%) with IR. Median age was 47 (26-72)
years with a median follow-up of 45 months. Pathologic complete response (pCR)
was noted in 49 (17.5%) cases. Overall 30-day complication rate was 13.2%.
Variables associated with complications included BMI (P < 0.0001), tobacco use (P
= 0.015), and adjuvant radiation (P = 0.025). Local-regional recurrence was 3.2%
and metastatic recurrence was 13.2%. Variables predicting recurrence risk were
pre-NAC tumor size (P < 0.001), residual tumor size (P = 0.002), Grade III (P =
0.002), HER-2 negative (P = 0.025), pre-NAC nodal disease (P = 0.05), and lack of
pCR (P = 0.045). CONCLUSION: Following NAC, risk factors for complications in
patients undergoing SSM/NSM with IR are high BMI, smoking, and adjuvant XRT.
SSM/NSM following NAC is associated with excellent local control. These data
support expanding the indications for NSM/SSM to include patients receiving NAC.
PMID- 28699270
TI - Does a multidisciplinary approach to voice and swallowing disorders improve
therapy adherence and outcomes?
PMID- 28699271
TI - Discounting: A practical guide to multilevel analysis of indifference data.
AB - Multilevel modeling provides the ability to simultaneously evaluate the
discounting of individuals and groups using indifference point data. After
considering the conditions when weaknesses emerge in estimating individual
discounting as a prelude to estimating group discounting, examples are provided
that indicate that multilevel modeling improves estimation in the presence of
variability and missing data, and when trying to fit two-parameter discounting
functions. Concrete examples of how to fit nonlinear multilevel models are
provided to help researchers in the adoption of these methods.
PMID- 28699272
TI - Aversive functions of response effort: Fact or artifact?
AB - Historically, effort has been viewed as aversive. Most supporting evidence comes
from studies demonstrating increased force/effort requirements reduce operant
responding. Changes in force/effort requirements, however, are often accompanied
by changes in response definition when mechanical devices are used to define the
response. As a consequence, responses measured at one point in a study may go
unmeasured at other points. In an alternative approach, we used a continuous
measurement strategy that provided a means to fix the threshold force defining
the response class and simultaneously allowed independent manipulation of the
force criteria required to produce reinforcement. Rats pressed a force transducer
according to a fixed-ratio 5 schedule of food delivery. The criterion force was
systematically increased and decreased; the threshold for response detection was
constant. When response rates included only criterion responses, overall rate
decreased when force requirements increased. By contrast, when all responses,
both those meeting force criteria and those that did not (above the threshold but
below the criteria for reinforcement) were included in the rate calculation,
increases in force increased response rate. Increases in force criteria also
increased the maximum force (g) and time-integral of force (g-s) of operant
behavior. Control conditions showed increases in responding could be explained by
the emergence of subcriterion responses, irrespective of force. We conclude that
prior results showing effort decreases response rates are due to an artifact
arising from inadvertent changes in response definitions. Increases in effort may
better be understood as changes in the response:reinforcer payoff owing to the
emergence of a subcriterion response class.
PMID- 28699273
TI - Improved autologous cortical bone harvest and viability with 2Flute otologic
burs.
AB - OBJECTIVES: To determine if 2Flute (Stryker Corporation, Kalamazoo, MI) otologic
burs improve the size, cellular content, and bone healing of autologous cortical
bone grafts harvested during canal wall reconstruction (CWR) tympanomastoidectomy
with mastoid obliteration. STUDY DESIGN: Institutional review board-approved
prospective cohort study. METHODS: Human autologous cortical bone chips were
harvested using various burs (4 and 6 mm diameter; multiflute, and 2Flute
[Stryker Corporation]) from patients undergoing CWR tympanomastoidectomy for the
treatment of chronic otitis media with cholesteatoma. Bone chip size, cell
counts, cellular gene expression, and new bone formation were quantified.
RESULTS: Bone chips were significantly larger when harvested with 2Flute (Stryker
Corporation) bur compared to multiflute burs at both 6 mm diameter (113 +/- 14
MUm2 vs. 66 +/- 8 MUm2 ; P < 0.05) and 4 mm diameter (70 +/- 8 MUm2 vs. 50 +/- 3
MUm2 ; P < 0.05). After 2 weeks in culture, cell numbers were significantly
higher when harvested with 2Flute (Stryker Corporation) bur compared to
multiflute burs at both 6 mm diameter (48.7 +/- 3 vs. 31.8 +/- 3 cells/MUg bone;
P < 0.05) and 4 mm diameter (27.6 +/- 1.2 vs. 8.8 +/- 1.2 cells/MUg bone; P <
0.05). Bone-derived cells express osteoblast markers (alkaline phosphatase,
osteocalcin). Cultured cells are able to form new bone in culture, and bone
formation is facilitated by the presence of bone chips. CONCLUSION: Use of 2Flute
(Stryker Corporation) otologic burs for human autologous cortical bone harvest
results in more viable bone fragments, with larger bone chips and more
osteoblasts. Future studies are needed to determine if this leads to improved
bone healing. LEVEL OF EVIDENCE: NA. Laryngoscope, 128:E41-E46, 2018.
PMID- 28699274
TI - Transplant center support for infectious diseases.
AB - BACKGROUND: Transplant Infectious Diseases (TID) is a rapidly growing
subspecialty, which has contributed significantly to improving patient outcomes
after transplantation. Obtaining institutional support to implement programs that
promote excellence in patient care remains a challenge for many non-surgical
transplant-related specialties. METHOD: We surveyed the membership of the
American Society of Transplantation Infectious Diseases Community of Practice to
assess characteristics of individual transplant programs and delineate current
patterns of institutional support of TID, with a goal of facilitating the
exchange of innovative funding ideas between transplant programs. RESULTS: Of 53
questionnaires returned, 36 programs reported the existence of a dedicated TID
service for adults. Of these, the ratio of dedicated TID providers to the number
of solid organ transplant patients transplanted annually ranged from 15:1 to
259:1. A total of 21% of responding programs indicated that they received no
support from their institution. Respondents from larger programs were more likely
to receive some type of programmatic support. CONCLUSION: Given that the presence
of expert TID input into patient care can improve outcomes through direct patient
management and transplant team education, we suggest that continued support of
the unbillable time contributed by TID practitioners is a critical part of
ensuring excellent outcomes after transplantation.
PMID- 28699275
TI - The concepts of asymmetric and symmetric power can help resolve the puzzle of
altruistic and cooperative behaviour.
AB - Evolutionary theory predicts competition in nature yet altruistic and cooperative
behaviour appears to reduce the ability to compete in order to help others
compete better. This evolutionary puzzle is usually explained by kin selection
where close relatives perform altruistic and cooperative acts to help each other
and by reciprocity theory (i.e. direct, indirect and generalized reciprocity)
among non-kin. Here, it is proposed that the concepts of asymmetry and symmetry
in power and dominance are critical if we are ever to resolve the puzzle of
altruism and cooperation towards non-kin. Asymmetry in power and dominance is
likely to emerge under competition in nature as individuals strive to gain
greater access to the scarce resources needed to survive and reproduce
successfully. Yet asymmetric power presents serious problems for reciprocity
theory in that a dominant individual faces a temptation to cheat in interactions
with subordinates that is likely to far outweigh any individual selective
benefits gained through reciprocal mechanisms. Furthermore, action taken by
subordinates to deter non-reciprocation by dominants is likely to prove
prohibitively costly to their fitness, making successful enforcement of
reciprocal mechanisms unlikely. It is also argued here that many apparently
puzzling forms of cooperation observed in nature (e.g. cooperative breeding in
which unrelated subordinates help dominants to breed) might be best explained by
asymmetry in power and dominance. Once it is recognized that individuals in these
cooperative interactions are subject to the constraints and opportunities imposed
on them by asymmetric power then they can be seen as pursuing a 'least bad'
strategy to promote individual fitness - one that is nevertheless consistent with
evolutionary theory. The concept of symmetric power also provides important
insights. It can inhibit reciprocal mechanisms in the sense that symmetric power
makes it easier for a cheat to appropriate common resources while incurring fewer
penalties. Nevertheless under certain restrictive conditions, symmetric power is
seen as likely to promote direct reciprocity through 'tit for tat'.
PMID- 28699276
TI - Y-chromosome and mtDNA variation confirms independent domestications and
directional hybridization in South American camelids.
AB - Investigations of genetic diversity and domestication in South American camelids
(SAC) have relied on autosomal microsatellite and maternally-inherited
mitochondrial data. We present the first integrated analysis of domestic and wild
SAC combining male and female sex-specific markers (male specific Y-chromosome
and female-specific mtDNA sequence variation) to assess: (i) hypotheses about the
origin of domestic camelids, (ii) directionality of introgression among domestic
and/or wild taxa as evidence of hybridization and (iii) currently recognized
subspecies patterns. Three male-specific Y-chromosome markers and control region
sequences of mitochondrial DNA are studied here. Although no sequence variation
was found in SRY and ZFY, there were seven variable sites in DBY generating five
haplotypes on the Y-chromosome. The haplotype network showed clear separation
between haplogroups of guanaco-llama and vicuna-alpaca, indicating two
genetically distinct patrilineages with near absence of shared haplotypes between
guanacos and vicunas. Although we document some examples of directional
hybridization, the patterns strongly support the hypothesis that llama (Lama
glama) is derived from guanaco (Lama guanicoe) and the alpaca (Vicugna pacos)
from vicuna (Vicugna vicugna). Within male guanacos we identified a haplogroup
formed by three haplotypes with different geographical distributions, the
northernmost of which (Peru and northern Chile) was also observed in llamas,
supporting the commonly held hypothesis that llamas were domesticated from the
northernmost populations of guanacos (L. g. cacilensis). Southern guanacos shared
the other two haplotypes. A second haplogroup, consisting of two haplotypes, was
mostly present in vicunas and alpacas. However, Y-chromosome variation did not
distinguish the two subspecies of vicunas.
PMID- 28699277
TI - Clinical evaluation of beta-tubulin real-time PCR for rapid diagnosis of
dermatophytosis, a comparison with mycological methods.
AB - Following our previous report on evaluation of the beta tubulin real-time PCR for
detection of dermatophytosis, this study aimed to compare the real-time PCR assay
with conventional methods for the clinical assessment of its diagnostic
performance. Samples from a total of 853 patients with suspected dermatophyte
lesions were subjected to direct examination (all samples), culture (499 samples)
and real-time PCR (all samples). Fungal DNA was extracted directly from clinical
samples using a conical steel bullet, followed by purification with a commercial
kit and subjected to the Taq-Man probe-based real-time PCR. The study showed that
among the 499 specimens for which all three methods were used, 156 (31.2%), 128
(25.6%) and 205 (41.0%) were found to be positive by direct microscopy, culture
and real-time PCR respectively. Real-time PCR significantly increased the
detection rate of dermatophytes compared with microscopy (288 vs 229) with 87%
concordance between the two methods. The sensitivity, specificity, positive
predictive value, and negative predictive value of the real-time PCR was 87.5%,
85%, 66.5% and 95.2% respectively. Although real-time PCR performed better on
skin than on nail samples, it should not yet fully replace conventional
diagnosis.
PMID- 28699278
TI - Regulatory T cells in skin.
AB - Foxp3+ CD4+ regulatory T (Treg) cells are a subset of immune cells that function
to regulate tissue inflammation. Skin is one of the largest organs and is home to
a large proportion of the body's Treg cells. However, relative to other tissues
(such as the spleen and gastrointestinal tract) the function of Treg cells in
skin is less well defined. Here, we review our understanding of how Treg cells
migrate to skin and the cellular and molecular pathways required for their
maintenance in this tissue. In addition, we outline what is known about the
specialized functions of Treg cells in skin. Namely, the orchestration of stem
cell-mediated hair follicle regeneration, augmentation of wound healing, and
promoting adaptive immune tolerance to skin commensal microbes. A comprehensive
understanding of the biology of skin Treg cells may lead to novel therapeutic
approaches that preferentially target these cells to treat cutaneous
autoimmunity, skin cancers and disorders of skin regeneration.
PMID- 28699279
TI - A new dominant haplotype of MC1R gene in Chinese black plumage chicken.
PMID- 28699280
TI - Dopamine D1 receptors induce apoptosis of osteosarcoma cells via changes of MAPK
pathway.
AB - This study explored the effects and mechanisms of dopamine D1 receptors (DR1)
activation on the apoptosis of osteosarcoma cells (OS732).The DR1 agonist SKF
38393 decreased the viability of OS732 cells and increased their rate of
apoptosis, whereas the DR1 antagonist SCH-23390 abolished the effects of SKF
38393. In OS732 cells, overexpression of DR1 increased the rate of apoptosis,
caspase-9 and -3 expression, and the release of cytochrome c (Cyt c), reduced Bcl
2 expression, inhibited extracellular signal-regulated kinase 1/2 (ERK1/2)
phosphorylation, and induced phosphorylation of p38 mitogen-activated protein
kinase (p38 MAPK) and c-Jun N-terminal kinase (JNK). These results suggest that
activation of DR1 induces osteosarcoma cell apoptosis via changes to the MAPK
pathway.
PMID- 28699281
TI - Promoting Cell Migration in Tissue Engineering Scaffolds with Graded Channels.
AB - Ideal bone scaffolds having good biocompatibility, good biodegradability, and
beneficial mechanical properties are the basis for bone tissue engineering.
Specifically, cell migration within 3D scaffolds is crucial for bone regeneration
of critical size defects. In this research, hydroxyapatite scaffolds with three
different types of architectures (tortuous, parallel, and graded channels) are
fabricated using the freeze-casting (ice-templating) method. While most studies
promote cell migration by chemical factors, it can be greatly enhanced by
introducing only graded channels as compared with tortuous or parallel channels.
The results provide insights and guidance in designing novel scaffolds to enhance
cell migration behavior for bone tissue regeneration.
PMID- 28699282
TI - Controllable Synthesis of Ultrathin NiCo2 O4 Nanosheets Incorporated onto
Composite Nanotubes for Efficient Oxygen Reduction.
AB - Exploring non-precious-metal-based oxygen reduction reaction (ORR)
electrocatalysts featuring high efficiency, low cost, and environmental
friendliness is of great importance for the broad applications of fuel cells and
metal-air batteries. In this work, ultrathin NiCo2 O4 nanosheets deposited on 1D
SnO2 nanotubes (SNT) were successfully fabricated through a productive
electrospinning technique followed by a sintering and low-temperature
coprecipitation strategy. This hierarchically engineered architecture has
ultrathin NiCo2 O4 nanosheets uniformly and fully erected on both walls of
tubular SNTs, which results in improved electrochemical activity as an ORR
catalyst, in terms of positive onset potential and high current density, as well
as superior tolerance to crossover effects and long-term durability with respect
to the commercial Pt/C catalyst. The excellent performance of SNT@NiCo2 O4
composites may originate from their rationally designed hierarchical tubular
nanostructure with completely exposed active sites and interconnected 1D networks
for efficient electron and electrolyte transfer; this makes these composite
nanotubes promising candidates to replace platinum-based catalysts for practical
fuel cell and metal-air battery applications.
PMID- 28699283
TI - Prospective evaluation of chronic organ damage in adult sickle cell patients: A
seven-year follow-up study.
AB - Organ damage in sickle cell disease (SCD) is a crucial determinant for disease
severity and prognosis. In a previous study, we analyzed the prevalence of SCD
related organ damage and complications in adult sickle cell patients. We now
describe a seven-year follow-up of this cohort.All patients from the primary
analysis in 2006 (n = 104), were included for follow-up. Patients were screened
for SCD-related organ damage and complications (microalbuminuria, renal failure,
elevated tricuspid regurgitation flow velocity (TRV) (>=2.5 m/seconds),
retinopathy, iron overload, cholelithiasis, avascular osteonecrosis, leg ulcers,
acute chest syndrome (ACS), stroke, priapism and admissions for vaso-occlusive
crises (VOC) biannually. Upon 7 years of follow-up, progression in the prevalence
of avascular osteonecrosis (from 12.5% to 20.4%), renal failure (from 6.7% to
23.4%), retinopathy (from 39.7% to 53.8%) was observed in the whole group. In
HbSS/HbSbeta0 -thal patients also progression in microalbuminuria (from 34% to
45%) and elevated TRV (from 40% to 48%) was observed while hardly any progression
in the prevalence of cholelithiasis, priapism, stroke or chronic ulcers was seen.
The proportion of patients with at least one episode of ACS increased in the
group of HbSS/HbSbeta0 -thal patients from 32% to 49.1%. In conclusion, 62% of
the sickle cell patients in this prospective cohort study developed a new SCD
related complication in a comprehensive care setting within 7 years of follow-up.
Although the hospital admission rate for VOC remained stable, multiple forms of
organ damage increased substantially. These observations underline the need for
continued screening for organ damage in all adult patients with SCD.
PMID- 28699284
TI - A monocyte-TNF-endothelial activation axis in sickle transgenic mice: Therapeutic
benefit from TNF blockade.
AB - Elaboration of tumor necrosis factor (TNF) is a very early event in development
of ischemia/reperfusion injury pathophysiology. Therefore, TNF may be a prominent
mediator of endothelial cell and vascular wall dysfunction in sickle cell anemia,
a hypothesis we addressed using NY1DD, S+SAntilles , and SS-BERK sickle
transgenic mice. Transfusion experiments revealed participation of abnormally
activated blood monocytes exerting an endothelial activating effect, dependent
upon Egr-1 in both vessel wall and blood cells, and upon NFkappaB(p50) in a blood
cell only. Involvement of TNF was identified by beneficial impact from TNF
blockers, etanercept and infliximab, with less benefit from an IL-1 blocker,
anakinra. In therapeutic studies, etanercept ameliorated multiple disturbances of
the murine sickle condition: monocyte activation, blood biomarkers of
inflammation, low platelet count and Hb, vascular stasis triggered by
hypoxia/reoxygenation (but not if triggered by hemin infusion), tissue production
of neuro-inflammatory mediators, endothelial activation (monitored by tissue
factor and VCAM-1 expression), histopathologic liver injury, and three surrogate
markers of pulmonary hypertension (perivascular inflammatory aggregates,
arteriolar muscularization, and right ventricular mean systolic pressure). In
aggregate, these studies identify a prominent-and possibly dominant-role for an
abnormal monocyte-TNF-endothelial activation axis in the sickle context. Its
presence, plus the many benefits of etanercept observed here, argue that pilot
testing of TNF blockade should be considered for human sickle cell anemia, a
challenging but achievable translational research goal.
PMID- 28699285
TI - Isobaric tags for relative and absolute quantification-based proteomic analysis
that reveals the roles of progesterone receptor, inflammation, and fibrosis for
slow-transit constipation.
AB - BACKGROUND AND AIM: Progesterone receptor, inflammation, neurotransmitter
expression, and fibrosis are involved in slow-transit constipation. The aim of
the present study was to examine whether patients with slow-transit constipation
have an overexpression of progesterone receptor and serotonin, which may impair
the fibrosis of muscularis propria in colorectal wall. METHODS: High-resolution
colon manometry was used to record the colorectal peristaltic contractions of the
proximal ascending and sigmoid colon in patients. Protein samples prepared from
frozen sigmoid colon tissue and the proximal margin of the ascending colon of
four female patients were compared using isobaric tags for relative and absolute
quantification labeling technique coupled to 2D liquid chromatography-tandem mass
spectrometry analysis. Immunohistochemical staining of progesterone receptor,
serotonin, and fibronectin was performed in paraffin-embedded sigmoid colon
tissues and the proximal margin of the ascending colon or ileum from 43 patients
with slow-transit constipation. RESULTS: Among these differentially regulated
proteins based on isobaric tags for relative and absolute quantification and
liquid chromatography-tandem mass spectrometry analysis, 56 proteins involved in
the response to progesterone, inflammation, matrix remodeling, fibrosis, and
muscle metabolism. Immunohistochemical staining confirmed that there was
significantly higher expression of progesterone receptor (t = 19.19, P = 0.000)
and serotonin (t = 13.52, P = 0.004) in sigmoid colon than in the proximal margin
of the ascending colon and ileum. Progesterone receptor and fibronectin
expression in the outer layer of muscularis propria were higher than in the
middle layer. CONCLUSIONS: These results demonstrate that progesterone receptor,
along with inflammation and fibrosis, may take part in slow-transit constipation
development.
PMID- 28699286
TI - Clinical anatomy of fecal incontinence in women.
AB - Fecal incontinence is a devastating condition that has a severe impact on quality
of life. This condition disproportionately affects women and its incidence is
increasing with the aging United States population. Fecal continence is
maintained by coordination of a functioning anal sphincter complex, intact
sensation of the anorectum, rectal compliance, and the ability to consciously
control defecation. Particularly important are the puborectalis sling of the
levator ani muscle complex and intact innervation of the central and peripheral
nervous systems. An understanding of the intricate anatomy required to maintain
continence and regulate defecation will help clinicians to provide appropriate
medical and surgical management and diminish the negative impact of fecal
incontinence. In this article, we describe the anatomic and neural basis of fecal
continence and normal defecation as well as changes that occur with fecal
incontinence in women. Clin. Anat. 30:901-911, 2017. (c) 2017 Wiley Periodicals,
Inc.
PMID- 28699287
TI - An alternative method for the analysis of melanin production in Cryptococcus
neoformans sensu lato and Cryptococcus gattii sensu lato.
AB - Melanin is an important virulence factor for several microorganisms, including
Cryptococcus neoformans sensu lato and Cryptococcus gattii sensu lato, thus, the
assessment of melanin production and its quantification may contribute to the
understanding of microbial pathogenesis. The objective of this study was to
standardise an alternative method for the production and indirect quantification
of melanin in C. neoformans sensu lato and C. gattii sensu lato. Eight C.
neoformans sensu lato and three C. gattii sensu lato, identified through URA5
methodology, Candida parapsilosis ATCC 22019 (negative control) and one Hortaea
werneckii (positive control) were inoculated on minimal medium agar with or
without L-DOPA, in duplicate, and incubated at 35 degrees C, for 7 days. Pictures
were taken from the third to the seventh day, under standardised conditions in a
photographic chamber. Then, photographs were analysed using grayscale images. All
Cryptococcus spp. strains produced melanin after growth on minimal medium agar
containing L-DOPA. C. parapsilosis ATCC 22019 did not produce melanin on medium
containing L-DOPA, while H. werneckii presented the strongest pigmentation. This
new method allows the indirect analysis of melanin production through pixel
quantification in grayscale images, enabling the study of substances that can
modulate melanin production.
PMID- 28699288
TI - Different characteristics of cell volume and intracellular calcium ion
concentration dynamics between the hippocampal CA1 and lateral cerebral cortex of
male mouse brain slices during exposure to hypotonic stress.
AB - The mechanism of brain edema is complex and still remains unclear. Our aim was to
investigate the regional differences of cell volume and intracellular Ca2+
concentration ([Ca2+ ]i ) dynamics during hypotonic stress in male mouse hemi
brain slices. Brain slices were loaded with the fluorescence Ca2+ indicator fura
2, and cell volume and [Ca2+ ]i in the lateral cerebral cortex (LCC) and
hippocampal CA1 (CA1) region were measured simultaneously during exposure to
hypotonic stress using Ca2+ insensitive (F360) and Ca2+ sensitive fluorescence
(F380), respectively. Brain cell swelling induced by hypotonic stress was
followed by a regulatory volume change that coincided with an increase in [Ca2+
]i . The degrees of change in cell volume and [Ca2+ ]i were significantly
different between the LCC and CA1. The increase in cell volume and [Ca2+ ]i in
the LCC, but not in the CA1, was decreased by the transient receptor potential
channel blockers LaCl3 and GdCl3 . The increase in [Ca2+ ]i in both the LCC and
CA1, was significantly decreased by the intracellular Ca2+ modulators
thapsigargin and xestospongin C. The K+ channel activator isoflurane and Cl-
channel blocker NPPB significantly decreased [Ca2+ ]i in the LCC. This study
demonstrated that, between cells located in the LCC and in the CA1, the
characteristics of brain edema induced by hypotonic stress are different. This
can be ascribed to the different contribution of volume sensitive G-protein
coupled receptor and stretch sensitive Ca2+ channels.
PMID- 28699289
TI - Contextually balanced medical education: realigning with global health care
delivery.
PMID- 28699290
TI - Choice in medical education.
PMID- 28699291
TI - Trainees' experiences and attitudes and the delivery of patient-centred care for
obesity.
PMID- 28699293
TI - Going from good to great: explicating norms through continuity in the clinical
workplace.
PMID- 28699294
TI - Plaudits and bouquets.
PMID- 28699295
TI - Effective teaching of manual skills to physiotherapy students: a randomised
clinical trial.
AB - CONTEXT: To date, despite the relevance of manual skills laboratories in
physiotherapy education, evidence on the effectiveness of different teaching
methods is limited. OBJECTIVES: Peyton's four-step and the 'See one, do one'
approaches were compared for their effectiveness in teaching manual skills.
METHODS: A cluster randomised controlled trial was performed among final-year,
right-handed physiotherapy students, without prior experience in manual therapy
or skills laboratories. The manual technique of C1-C2 passive right rotation was
taught by different experienced physiotherapist using Peyton's four-step approach
(intervention group) and the 'See one, do one' approach (control group).
Participants, teachers and assessors were blinded to the aims of the study.
Primary outcomes were quality of performance at the end of the skills
laboratories, and after 1 week and 1 month. Secondary outcomes were time required
to teach, time required to perform the procedure and student satisfaction.
RESULTS: A total of 39 students were included in the study (21 in the
intervention group and 18 in the control group). Their main characteristics were
homogeneous at baseline. The intervention group showed better quality of
performance in the short, medium and long terms (F1,111 = 35.91, p < 0.001).
Both groups demonstrated decreased quality of performance over time (F2,111 =
12.91, p < 0.001). The intervention group reported significantly greater mean +/-
standard deviation satisfaction (4.31 +/- 1.23) than the control group (4.03 +/-
1.31) (p < 0.001). Although there was no significant difference between the two
methods in the time required for teaching, the time required by the intervention
group to perform the procedure was significantly lower immediately after the
skills laboratories and over time (p < 0.001). CONCLUSIONS: Peyton's four-step
approach is more effective than the 'See one, do one' approach in skills
laboratories aimed at developing physiotherapy student competence in C1-C2
passive mobilisation.
PMID- 28699296
TI - Long-lasting contribution of dopamine in the nucleus accumbens core, but not
dorsal lateral striatum, to sign-tracking.
AB - The attribution of incentive salience to reward-paired cues is dependent on
dopamine release in the nucleus accumbens core (NAcC). These dopamine signals
conform to traditional reward-prediction error signals and have been shown to
diminish with time. Here we examined whether the diminishing dopamine signal in
the NAcC has functional implications for the expression of sign-tracking, a
Pavlovian conditioned response indicative of the attribution of incentive
salience to reward-paired cues. Food-restricted male Sprague Dawley rats were
trained in a Pavlovian paradigm in which an insertable lever predicted delivery
of food reward in a nearby food cup. After 7 or 14 training sessions, rats
received infusions of saline, the dopamine antagonist flupenthixol, or the GABA
agonists baclofen and muscimol into the NAcC or the dorsal lateral striatum
(DLS). Dopamine antagonism within the NAcC attenuated sign-tracking, whereas
reversible inactivation did not affect sign-tracking but increased non-specific
food cup checking behaviors. Neither drug in the DLS affected sign-tracking
behavior. Critically, extended training did not alter these effects. Although
extended experience with an incentive stimulus may reduce cue-evoked dopamine in
the NAcC, this does not remove the dependence on dopamine in this region to
promote Pavlovian cue approach nor result in the recruitment of dorsal lateral
striatal systems for this behavior. These data support the notion that dopamine
within the mesoaccumbal system, but not the nigrostriatal system, contributes
critically to incentive motivational processes independent of the length of
training.
PMID- 28699297
TI - Cost-effectiveness analysis of anidulafungin vs fluconazole for the treatment of
invasive candidiasis (IC) in Turkey.
AB - Anidulafungin has been shown to be non-inferior to, and possibly more
efficacious, than fluconazole in treating patients with invasive candidiasis
(IC). This study aimed to determine the cost-effectiveness of anidulafungin vs
fluconazole for treatment of IC in the Turkish setting. A decision analytic model
was constructed to depict downstream economic consequences of using anidulafungin
or fluconazole for treatment of IC in the Turkish hospitals. Transition
probabilities (ie treatment success, observed or indeterminate treatment
failures) were obtained from a published randomised clinical trial. Cost inputs
were from the latest Turkish resources. Data not available in the literature were
estimated by expert panels. Sensitivity analyses were performed to assess the
robustness of the model outcome. While anidulafungin [TL 17 171 (USD 4589)]
incurred a higher total cost than fluconazole [TL 8233 (USD 2200) per treated
patient, treatment with anidulafungin was estimated to save an additional 0.58
life-years, with an incremental cost-effectiveness ratio of TL 15 410 (USD 4118)
per life-years saved. Drug acquisition cost and hospitalisation were the main
cost drivers for anidulafungin and fluconazole arms respectively. The model
findings were robust over a wide range of input variables except for
anidulafungin drug cost. Anidulafungin appears to be a cost-effective therapy in
treating IC from the Turkish hospital perspective.
PMID- 28699298
TI - Tailored Design of Bicontinuous Gyroid Mesoporous Carbon and Nitrogen-Doped
Carbon from Poly(ethylene oxide-b-caprolactone) Diblock Copolymers.
AB - Highly ordered mesoporous resol-type phenolic resin and the corresponding
mesoporous carbon materials were synthesized by using poly(ethylene oxide-b
caprolactone) (PEO-b-PCL) diblock copolymer as a soft template. The self
assembled mesoporous phenolic resin was found to form only in a specific resol
concentration range of 40-70 wt % due to an intriguing balance of hydrogen
bonding interactions in the resol/PEO-b-PCL mixtures. Furthermore, morphological
transitions of the mesostructures from disordered to gyroid to cylindrical and
finally to disordered micelle structure were observed with increasing resol
concentration. By calcination under nitrogen atmosphere at 800 degrees C, the
bicontinuous mesostructured gyroid phenolic resin could be converted to
mesoporous carbon with large pore size without collapse of the original
mesostructure. Furthermore, post-treatment of the mesoporous gyroid phenolic
resin with melamine gave rise to N-doped mesoporous carbon with unique electronic
properties for realizing high CO2 adsorption capacity (6.72 mmol g-1 at 0
degrees C).
PMID- 28699299
TI - "Matching" consent to purpose: The example of the Matchmaker Exchange.
AB - The Matchmaker Exchange (MME) connects rare disease clinicians and researchers to
facilitate the sharing of data from undiagnosed patients for the purpose of novel
gene discovery. Such sharing raises the odds that two or more similar patients
with candidate genes in common may be found, thereby allowing their condition to
be more readily studied and understood. Consent considerations for data sharing
in MME included both the ethical and legal differences between clinical and
research settings and the level of privacy risk involved in sharing varying
amounts of rare disease patient data to enable patient matches. In this
commentary, we discuss these consent considerations and the resulting MME Consent
Policy as they may be relevant to other international data sharing initiatives.
PMID- 28699300
TI - Angiogenic, inflammatory and immunologic markers in predicting response to
sunitinib in metastatic renal cell carcinoma.
AB - The objective of this prospective study was to identify baseline angiogenic and
inflammatory markers in serum as well as the baseline levels of immune cells in
whole blood to predict progression-free survival in patients with metastatic
renal cell carcinoma treated with sunitinib. Blood samples were collected at
baseline in all 90 patients to analyze serum angiogenic and inflammatory markers
together with peripheral blood immunological marker. The association between each
marker and sunitinib efficacy was analyzed. Univariate and multivariate Cox
proportional model analyses were used to assess the correlation between those
markers with survival. Baseline levels of interleukin-6, interleukin-8, high
sensitivity C-reactive protein and myeloid-derived suppressor cells were
significantly higher in patients who progressed when compared with those with
clinical benefit. Analysis by the Cox regression model showed that baseline
interleukin-8, high sensitivity C-reactive protein and percentage of T helper
type 1 cells were significantly associated with progression-free survival in
univariate analysis. Furthermore, in multivariate analysis, those three markers
were independent indices to predict progression-free survival. In conclusion,
angiogenic (interleukin-8), inflammatory (interleukin-6, high sensitivity C
reactive) and immunologic (myeloid-derived suppressor cells, percentage of T
helper type 1 cells) markers at baseline would predict the response to sunitinib
therapy and/or disease progression in patients with metastatic renal cell
carcinoma.
PMID- 28699301
TI - Prospective Evaluation of Patient Usage of Above and Below Threshold Waveforms
With Traditional Spinal Cord Stimulation Devices.
AB - OBJECTIVES: Spinal cord stimulation (SCS) is an efficacious therapy used to treat
chronic pain. The type of SCS programming is important in improving patients'
quality of life and overall satisfaction. In this study, 19 patients who
underwent SCS with traditional devices were given between 4 and 6 programs
including programs with stimulation below sensory threshold and above sensory
threshold. Usage patterns and preferences were assessed. METHODS: SCS patients
were given 4-6 programs, some above sensory threshold and some below threshold
immediately postoperatively after permanent implantation. Usage patterns of
different programs were documented, including percent of time that the settings
were used and preference for above threshold vs. below threshold settings during
sleeping, walking, sitting, and vigorous activity. Improvements at three months
in Oswestry disability index (ODI), numeric rating scale (NRS), Beck depression
inventory (BDI), McGill pain questionnaire (MPQ), pain catastrophizing scale
(PCS), insomnia severity index (ISI), and Epworth sleepiness scale (ESS) were
evaluated. RESULTS: Patients were all trialed on above sensory threshold
programs. Six weeks after implantation, most patients preferred above threshold
stimulation (74%) vs. below threshold waveforms (21%). Patient diagnosis,
type/location of lead or recharging burden played no role in patient preference.
Above threshold patients had significantly better improvement in BDI scores than
did below threshold patients (p < 0.05) at three-month follow-up but also had
worse ESS scores (p < 0.05). Above threshold stimulation was preferred for
walking and sitting (p < 0.05). CONCLUSIONS: Results indicate that when given the
option between waveforms inducing paresthesias and those that do not, SCS
patients tend to prefer waveforms that induce paresthesias. Among users of above
threshold waveforms, there was preference for these settings during walking and
sitting. There was a trend for below threshold preference in vigorous activity
and sleeping.
PMID- 28699302
TI - Runx3 inhibits melanoma cell migration through regulation of cell shape change.
AB - The transcription factor Runx3 is a known tumor suppressor gene, and its
expression is frequently lost in melanoma. However, the potential contribution of
the loss of Runx3 expression to melanoma development and progression remains
unclear. In this in vitro study, we demonstrated that ectopic Runx3 re-expression
in B16-F10 melanoma cells changed the cell shape from elongated and branched to
spread and unbranched, which enhanced stress fiber formation, increased the
number of mature and fibrillar focal adhesions, and up-regulated fibronectin
expression. In association with the cell shape change, the Runx3 re-expression in
B16-F10 melanoma cells inhibited cell migration. Moreover, the phenotype of the
Runx3 induced cell shape change was partially resembled when the melanoma cells
were cultured on a fibronectin-coated coverslip, suggesting that fibronectin may
mediate the Runx3 induced cell shape change of the melanoma cells. Taken
together, our findings suggest that Runx3 may regulate cell shape to inhibit
melanoma cell migration partly through enhancing stress fiber formation and ECM
protein production. Our present study provides further evidence for the idea that
cell shape change is potentially correlated with melanoma development and
progression.
PMID- 28699303
TI - Should patients with primary snoring be screened for carotid artery stenosis?
PMID- 28699304
TI - Immune checkpoint inhibitors: Navigating a new paradigm of treatment toxicities.
AB - Immune checkpoint inhibitors have recently emerged as an exciting new treatment
paradigm across a broad spectrum of malignancies. This new class of agents also
challenges oncologists with a unique set of immune-based toxicities. Early
recognition and precise management of these toxicities can result in better
outcomes, with minimization of toxicity and harm to the patient. This article
provides a comprehensive review of immune-based toxicities caused by immune
checkpoint inhibitors, including recommendations for their investigation and
guidelines for specific management.
PMID- 28699305
TI - Enhancement of the luteinising hormone surge by male olfactory signals is
associated with anteroventral periventricular Kiss1 cell activation in female
rats.
AB - Olfactory stimuli play an important role in regulating reproductive functions in
mammals. The present study investigated the effect of olfactory signals derived
from male rats on kisspeptin neuronal activity and luteinising hormone (LH)
secretion in female rats. Wistar-Imamichi strain female rats were ovariectomised
(OVX) and implanted with preovulatory levels of 17beta-oestradiol (E2 ). OVX+E2
rats were killed 1 hour after exposure to either: clean bedding, female-soiled
bedding or male-soiled bedding. Dual staining for Kiss1 mRNA in situ
hybridisation and c-Fos immunohistochemistry revealed that the numbers of Kiss1
expressing cells and c-Fos-immunopositive Kiss1-expressing cells in the
anteroventral periventricular nucleus (AVPV) were significantly higher in OVX+E2
rats exposed to male-soiled bedding than those of the other groups. No
significant difference was found with respect to the number of c-Fos
immunopositive Kiss1-expressing cells in the arcuate nucleus and c-Fos
immunopositive Gnrh1-expressing cells between the groups. The number of c-Fos
immunopositive cells was also significantly higher in the limbic system
consisting of several nuclei, such as the bed nucleus of the stria terminalis,
the cortical amygdala and the medial amygdala, in OVX+E2 rats exposed to male
soiled bedding than the other groups. OVX+E2 rats exposed to male-soiled bedding
showed apparent LH surges, and the peak of the LH surge and area under the curve
of LH concentrations in the OVX+E2 group were significantly higher than those of
the other two groups. These results suggest that olfactory signals derived from
male rats activate AVPV kisspeptin neurones, likely via the limbic system,
resulting in enhancement of the peak of the LH surge in female rats. Taken
together, the results of the present study suggests that AVPV kisspeptin neurones
are a target of olfactory signals to modulate LH release in female rats.
PMID- 28699306
TI - Strategies for building a successful ultrasound guided FNA practice in department
of pathology-Experience at a university hospital.
AB - INTRODUCTION: Although pathology services focused on fine needle aspiration (FNA)
biopsy of superficial palpable masses with on-site cytological evaluation are
available in a wide range of clinical and academic settings, the addition of
ultrasound (US) guidance into FNA practice by a cytopathologist group can be
challenging. An US-FNA service provided by a cytopathologist in the department of
Pathology is a relatively new practice in the field of medicine. This report
summarizes our experience and strategies in achieving this objective and our
successful preliminary results. MATERIALS AND METHODS: The US-FNA service
includes (1) an FNA procedure to be performed by a cytopathologist under US
guidance; (2) onsite adequacy evaluation and diagnosis to be done by the same
cytopathologist; and immediate patient consultation and sample triaging carried
out by the same cytopathologist in an FNA suite within the department of
Pathology. The FNA suite including a procedure room equipped with a portable US
machine, an exam/procedure table, a mobile cabinet with FNA supplies, a counter
with sink, and a reception room with waiting area is set-up. RESULTS: The
establishment of the US-FNA service is successful. There is an incremental growth
of the service over the first 8 months. Among the 114 cases performed during the
first 8 months, the case type distribution is shown to be 50% thyroid nodules,
33% lymph nodes, 5.5% salivary gland masses, 3.5% breast masses, and 8% soft
tissue masses. CONCLUSIONS: The authors' initial 8 months experience and
strategies in setting up a new US-FNA practice in a new institution are discussed
to highlight obstacles encountered and approaches that promoted the successful
establishment of a new service. A conservative approach, focusing on building
partnerships with existing clinical services, can be successfully implemented in
most institutions, if appropriate strategies are applied. The main strategy is to
ensure that the best interests of patients remain the primary focus and that
everything possible is done to improve the quality and effectiveness of patient
care by providing the best possible diagnostic US-FNA service, to enable optimal
clinical management.
PMID- 28699307
TI - New Surgical Instruction Method for Homium Laser Enucleation of the Prostate,
"Hand-Grab Navigated Technique," to Shorten the Learning Curve: The Results of
Multicenter Analysis.
AB - OBJECTIVES: To introduce a new surgical mentorship, the "hand-grab navigated
technique," to shorten the learning curve for Holmium laser enucleation of the
prostate. METHODS: Patients with benign prostatic hyperplasia were managed at six
institutions with Holmium laser enucleation of the prostate. An analysis was done
in the 200 of these patients (the set of first 20 patients treated with Holmium
laser enucleation of the prostate by 10 surgeons) who were sorted into two groups
depending on the surgeon's instructional group. Surgeons in group I learned
Holmium laser enucleation of the prostate by self-study by using videos and
written information, whereas those in group II were instructed by "the hand-grab
navigated technique" along with the self-study. To evaluate the efficiency of
hand-grab navigated technique, enucleation and morcellation efficiencies between
the two groups were compared. RESULTS: The mean prostate volume was 49.5 +/- 23.8
and 51.1 +/- 25.2 g in group I and II, respectively, showing no significant
difference. The enucleation efficiency was significantly greater (P = 0.01) in
group II (0.35 +/- 0.20 g/min) than in group I (0.21 +/- 0.12 g/min).
Morcellation efficiency was also significantly greater (P = 0.03) in group II
(3.08 +/- 3.27 g/min) than in group I (2.43 +/- 2.68 g/min). CONCLUSION: The
learning curve for Holmium laser enucleation of the prostate can be shortened
with the "hand-grab navigated technique" when combined with the self-study.
PMID- 28699309
TI - Corrigendum.
PMID- 28699308
TI - Phospholipid Capped Mesoporous Nanoparticles for Targeted High Intensity Focused
Ultrasound Ablation.
AB - The mechanical effects of cavitation can be effective for therapy but difficult
to control, thus potentially leading to off-target side effects in patients.
While administration of ultrasound active agents such as fluorocarbon
microbubbles and nanodroplets can locally enhance the effects of high intensity
focused ultrasound (HIFU), it has been challenging to prepare ultrasound active
agents that are small and stable enough to accumulate in tumors and internalize
into cancer cells. Here, this paper reports the synthesis of 100 nm nanoparticle
ultrasound agents based on phospholipid-coated, mesoporous, hydrophobically
functionalized silica nanoparticles that can internalize into cancer cells and
remain acoustically active. The ultrasound agents produce bubbles when subjected
to short HIFU pulses (~6 us) with peak negative pressure as low as ~7 MPa and at
particle concentrations down to 12.5 ug mL-1 (7 * 109 particles mL-1 ).
Importantly, ultrasound agents are effectively uptaken by cancer cells without
cytotoxic effects, but HIFU insonation causes destruction of the cells by the
acoustically generated bubbles, as demonstrated by (2,3-bis-(2-methoxy-4-nitro-5
sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) and lactate dehydrogenase
assays and flow cytometry. Finally, it is showed that the HIFU dose required to
effectively eliminate cancer cells in the presence of ultrasound agents causes
only a small temperature increase of ~3.5 degrees C.
PMID- 28699310
TI - The effects of sEH inhibitor on depression-like behavior and neurogenesis in male
mice.
AB - Currently antidepressants take several weeks to be effective, which is one of the
main reasons why patients with depression quit therapy. In the present study, we
examine the acute and subacute effects of soluble epoxide hydolase (sEH)
inhibitor (sEHI), a compound shown to have antidepressant effects, on mice. We
found that acute administration of sEHI TPPU decreases immobility time in the
forced swimming test and reduces latency to feed in the novelty suppressed
feeding test in adult male mice. Intraperitoneal administration of TPPU for seven
days also increased interaction time of socially defeated mice in the social
defeat test. Hippocampal BDNF expression and cell proliferation in the dentate
gyrus increased six and 24 hours after TPPU treatment, respectively. Improvement
in antidepressant behavior and cell proliferation were inhibited by BDNF-trkB
antagonist K252a, which suggests that anti-depressant effects of sEHI may be
involved in BDNF signaling. Taken together, our findings suggest that sEHI may
provide a rapid antidepressant effect through alterations to BDNF-trkB signaling
in the hippocampus and may provide an alternative to current slow-acting
antidepressants. (c) 2017 Wiley Periodicals, Inc.
PMID- 28699312
TI - Erratum.
PMID- 28699311
TI - Ganciclovir-Resistant Cytomegalovirus Infection in Abdominal Solid Organ
Transplant Recipients: Case Series and Review of the Literature.
AB - Ganciclovir-resistant cytomegalovirus (GR-CMV) is emerging as a significant
infection in the abdominal transplant population. GR-CMV is difficult to manage,
and treatment options are limited. We report a descriptive case series of 15
patients who had documented GR-CMV at our center and review the literature on
treatment of GR-CMV. The first case in this series was detected in 2012; the
majority of cases occurred after January 1, 2014, with approximately 50%
occurring in 2015. UL97 and UL54 viral genome mutations were present in 100% and
40% of CMV-infected patients, respectively. GR-CMV infection occurred <= 1 year
posttransplantation in 11 patients (73%). All patients experienced dose reduction
of valganciclovir (the oral prodrug of ganciclovir) before the development of GR
CMV. Initial treatment for GR-CMV included a variety of regimens, all including
reduction in maintenance immunosuppression. Of the 6 patients with detectable GR
CMV by polymerase chain reaction (PCR) who were discharged without GR-CMV
treatment and had a length of stay (LOS) less than 14 days, 83% were subsequently
readmitted for treatment of GR-CMV within 2 months (60% in < 20 days); none
received leflunomide. Of six patients with a LOS >= 14 days, 80% had CMV PCR
below quantification on hospital discharge, and only one patient was readmitted
in less than 20 days; 83% received leflunomide. Following GR-CMV, there was a 50%
rejection incidence, 27% graft loss, and 20% mortality. For patients with more
than three admissions for GR-CMV treatment, 100% had a major complication: 60%
rejection, 20% graft loss, and 40% mortality. Common clinical characteristics of
patients with GR-CMV included high-risk serostatus, lymphocyte depletion, and
history of valganciclovir dose reduction. Overall, outcomes were poor. It appears
that hospital readmission rate was reduced when CMV was treated to negativity
with an initial treatment regimen of reduced immunosuppression, foscarnet,
intravenous immunoglobulins, and leflunomide.
PMID- 28699313
TI - Corrigendum.
PMID- 28699314
TI - Erratum.
PMID- 28699315
TI - Response to Letter to the Editor: NMO 00164-2017.
PMID- 28699316
TI - The dilemma of using global signal regression in resting-state fMRI study.
PMID- 28699317
TI - Obituary.
PMID- 28699319
TI - News from the editors of Neurogastroenterology and Motility.
PMID- 28699318
TI - High-resolution anorectal manometry: An expensive hobby or worth every penny?
AB - Introduced approximately 10 years ago, high-resolution manometry catheters have
fostered interest in anorectal manometry. This review, which accompanies two
articles in this issue of Neurogastroenterology and Motility, reviews the
methods, clinical indications, utility, and pitfalls of anorectal manometry and
revisits the American Gastroenterological Association (AGA) Medical Position
Statement on Anorectal Testing Techniques, which was last published in 1999. High
resolution manometry provides a refined assessment of the anorectal pressure
profile, obviates the need for station pull-through maneuvers, and minimizes
movement artifacts. In selected cases, this refined assessment may be useful for
identifying structural abnormalities or anal weakness. However, many manometry
patterns that were previously regarded as abnormal are also observed in a
majority of healthy patients, which substantially limits the utility of manometry
for identifying defecatory disorders. It is our impression that most conclusions
of the AGA medical position statement from 1999 remain valid today. High
resolution techniques have not substantially affected the number of publications
on or management of anorectal disorders. The ongoing efforts of an international
working group to standardize techniques for anorectal manometry are welcome.
Although high-resolution manometry is more than an expensive hobby, improvements
in catheter design and further research to rigorously define and evaluate these
techniques are necessary to determine if they are worth every penny.
PMID- 28699320
TI - A three plus three parameters mechanistic model for viral filtration.
AB - Viral filtration is an expensive regulatory requirement in downstream processing
of monoclonal antibodies (mAbs). This process step is typically operated with an
overdesigned filter in order to account for any batch to batch variability in the
filter, as well as the feed characteristics. Here, we propose a simple, six
parameter mechanistic model for viral filtration where three parameters are
membrane-specific while the other three depend on feed characteristics and
membrane-feed interactions. Viruses are considered as passive particles which are
retained by the membrane on the basis of size exclusion. The model envisages that
the viral filter contains two kind of pores: virus-retentive, small-sized pores
and non-retentive, large-sized pores. The small-sized pores get blocked during
filtration resulting in decrease in active membrane area, while the large-sized
pores get constricted during filtration. The length of constricted part increases
during filtration and contributes to increase in hydraulic resistance of the
filter. Rate of these processes (blocking and constriction) are assumed to be
proportional to the instantaneous rate of retention of the viral particles. The
general nature of the model is validated with the experimental data on viral
filtration for four different commercial membranes used in biotech industries as
well as different model viruses. The proposed model has been demonstrated to
describe the behavior of filters with very good accuracy. The best-fit model
parameter values indicate about the various phenomena that are responsible for
differences in the behavior of the membranes as well as change in retention and
flux with feed concentration. The proposed model can be used for improving design
of virus filters as well as in appropriate sizing of the filters during
processing. (c) 2017 American Institute of Chemical Engineers Biotechnol. Prog.,
33:1538-1547, 2017.
PMID- 28699321
TI - Indolizine-Squaraines: NIR Fluorescent Materials with Molecularly Engineered
Stokes Shifts.
AB - The development of deep red and near infrared emissive materials with high
quantum yields is an important challenge. Several classes of squaraine dyes have
demonstrated high quantum yields, but require significantly red-shifted
absorptions to access the NIR window. Additionally, squaraine dyes have typically
shown narrow Stokes shifts, which limits their use in living biological imaging
applications due to dye emission interference with the light source. Through the
incorporation of indolizine heterocycles we have synthesized novel indolizine
squaraine dyes with increased Stokes shifts (up to >0.119 eV, >50 nm increase)
and absorptions substantially further into the NIR region than an indoline
squaraine benchmark (726 nm versus 659 nm absorption maxima). These materials
have shown significantly enhanced water solubility, which is unique for squaraine
dyes without water-solubilizing substituents. Absorption, electrochemical,
computational, and fluorescence studies were undertaken and exceptional
fluorescence quantum yields of up 12 % were observed with emission curves
extending beyond 850 nm.
PMID- 28699322
TI - A Respiratory Marker Derived From Left Vagus Nerve Signals Recorded With
Implantable Cuff Electrodes.
AB - OBJECTIVE: Left vagus nerve (LVN) stimulation (LVNS) has been tested for lowering
the blood pressure (BP) in patients with resistant hypertension (RH). Whereas,
closed-loop LVNS (CL-LVNS) driven by a BP marker may be superior to open-loop
LVNS, there are situations (e.g., exercising) when hypertension is normal.
Therefore, an ideal anti-RH CL-LVNS system requires a variable to avoid
stimulation in such conditions, for example, a respiratory marker ideally
extracted from the LVN. As the LVN conducts respiratory signals, this study aimed
to investigate if such signals can be recorded using implantable means and if a
marker to monitor respiration could be derived from such recordings. MATERIALS
AND METHODS: The experiments were performed in 14 anesthetized pigs. Five pigs
were subjected to changes of the respiratory frequency and nine to changes of the
respiratory volume. The LVN electroneurogram (VENG) was recorded using two cuff
electrodes and the respiratory cycles (RC) using a pressure transducer. To
separate the afferent and efferent VENGs, vagotomy was performed between the
cuffs in the first group of pigs. The VENG was squared to derive respiration
related neural profiles (RnPs) and their correlation with the RCs was
investigated in regard to timing and magnitude parameters derived from the two
waveforms. RESULTS: The RnPs were morphologically similar with the RCs and the
average RnPs represented accurate copies of the average RCs. Consequently, the
lung inflation/deflation RC and RnP components had the same duration, the
respiratory frequency changes affected in the same way both waveforms and the RnP
amplitude increased linearly with the lung inflation in all tested pigs (R2
values between 0.85 and 0.99). CONCLUSIONS: The RnPs comprise information
regarding the timing and magnitude of the respiratory parameters. As those LVN
profiles were derived using implantable means, this study indicates that the RnPs
could serve as respiratory markers in implantable systems.
PMID- 28699323
TI - Intra-procedural continuous dialysis to facilitate interventional catheterization
in pediatric patients with severe renal failure.
AB - BACKGROUND: Interventional catheterization procedures may be needed for patients
with severe renal failure who are dependent on dialysis. To avoid the risk of
fluid overload and electrolyte derangement during complex procedures in this
oliguric/anuric patient population, we performed intra-procedural dialysis,
either continuous renal replacement therapy (CRRT) or continous cycling
peritoneal dialysis (CCPD). METHODS: We performed a retrospective review of a
cohort of pediatric patients, ages 0-18 years, with dialysis-dependent renal
failure who received CRRT or CCPD during catheterization procedures from January
2013 to March 2016. RESULTS: Eight patients underwent a total of nine
interventional catheterization procedures while receiving intra-procedural
dialysis. Median age was 4.5 years (range 8 months to 17 years) and weight, 11.6
kg (11.2-62.6 kg). Six patients had end-stage renal disease (ESRD) and two
patients had acute kidney injury (AKI), one due to hepatorenal syndrome and one
due to multifactorial causes associated with congenital heart disease. The most
common reason for catheterization was occlusive venous thrombosis requiring
recanalization. CRRT was used during five cases and CCPD during four cases.
Median procedure time was 337 min (95-651 min) and median contrast dose 4.2 mL kg
1 (1.2-8.2 mL kg-1 ). Euvolemia was maintained based on pre- and post
catheterizations weights, and no significant electrolyte abnormalities occurred
based on lab monitoring during and post-procedure. CONCLUSIONS: Intra-procedural
dialysis using CRRT or CCPD enables even small pediatric patients with severe
renal failure to undergo long and complex interventional catheterizations by
reducing the risk of fluid overload and electrolyte abnormalities. Collaboration
between nephrology, cardiology, and dialysis teams is necessary for successful
management of this challenging patient population.
PMID- 28699324
TI - Corneal endothelial cell loss and corneal biomechanical characteristics after two
step sequential or combined phaco-vitrectomy surgery for idiopathic epiretinal
membrane.
AB - PURPOSE: To assess the impact of sequential and combined surgery [cataract
surgery and 23-gauge pars plana vitrectomy (PPV) with peeling] on corneal
endothelium cell density (CED) and corneal biomechanical characteristics.
METHODS: Phakic eyes with epiretinal membrane (ERM) were prospectively allocated
to (i) cataract surgery and subsequent PPV (CAT group), (ii) PPV and subsequent
cataract surgery (VIT group) or (iii) phacovitrectomy (COMBI group). Eyes were
examined at baseline, 1 month after each surgery, and at 3 and 12 months follow
up. Corneal endothelium cell density (CED) was assessed with non-contact specular
microscopy. Pachymetry [central cornea thickness (CCT)], keratometry and cornea
volume (CV) were measured with Pentacam Scheimpflug camera. Primary outcome was
change in CED after 12 months; secondary outcomes were changes in CCT and CV
after 12 months. RESULTS: Sixty-two eyes were enrolled and allocated to the three
groups. The mean preoperative CED was 2776, 2794 and 2653 cells/mm2, which
decreased significantly at 12 months by 15.3, 20.0 and 19.3% in the CAT, VIT and
COMBI group. There was no significant difference in percentage cell loss between
the groups at final follow-up. The CED decreased significantly after cataract
surgery, but was unaffected by PPV. Central cornea thickness (CCT) increased by
10 MUm (p = 0.005) and CV by 1.38 mm3 (2.3%, p < 0.001) in the COMBI group. There
were no significant differences in CCT or CV between the groups at final follow
up. CONCLUSION: Combined and sequential surgery in ERM leads to a small decrease
in CED. Performing cataract surgery before, after or in combination with
vitrectomy did not make any significant difference with respect to final CED, CCT
or CV.
PMID- 28699327
TI - Acute-Onset Severe Occipital Neuralgia Associated With High Cervical Lesion in
Patients With Neuromyelitis Optica Spectrum Disorder.
AB - OBJECTIVE: To address occipital neuralgia in patients with neuromyelitis optica
spectrum disorder (NMOSD). BACKGROUND: NMOSD is an inflammatory demyelinating
disease that commonly presents with pain; however, headache symptoms have
received little attention. METHODS: We presented three cases of NMOSD in which
the patients experienced acute-onset, severe, and steroid-responsive occipital
neuralgia. All patients provided consent to use their demographic and imaging
data retrospectively. RESULTS: In all three cases, MRI revealed a new high
intensity area in the cervical cord at the C1-C3 level of the spine, which was
diminished in two of the three cases after corticosteroid pulse therapy.
CONCLUSION: Our cases support the recognition of NMOSD as a cause of secondary
headache. As patients with NMOSD experience severe occipital neuralgia, a relapse
should be considered and a cervical MRI should be performed.
PMID- 28699326
TI - Gamma-Aminobutyric Acid (Gaba) Receptors Rho (Gabrr) Gene Polymorphisms and Risk
for Migraine.
AB - BACKGROUND/OBJECTIVES: The possible role of gammaaminobutyric acid (GABA) in the
pathogenesis of migraine has been suggested by a number of biochemical,
pharmacological, neurophysiological and experimental data. We investigated the
possible association between the most common single nucleotide polymorphisms
(SNPs) in the GABA receptor rho1, 2, and 3 genes (GABRR1, GABRR2, and GABRR3) and
the risk of developing migraine. METHODS: The frequency of GABRR1 rs12200969,
GABRR1 rs1186902, GABRR2 rs282129, and GABRR3 rs832032 genotypes and allelic
variants were studied in a case-control association study involving 197 patients
with migraine and 278 healthy controls by means of a TaqMan-based qPCR Assay. We
also studied the possible influence of gender, age at onset of migraine, positive
family history of migraine, presence or absence of aura, and triggering of
migraine by ethanol on the frequency of the genotypes. RESULTS: The frequencies
of the genotypes and allelic variants of the 4 SNPs were similar in migraine
patients and controls. Gender, positive family history of migraine, presence or
absence of aura, and triggering of migraine attacks by ethanol did not influence
the frequency of these genotypes. Carriers of the minor allele of the rs1186902
SNP showed a trend towards later onset of migraine. CONCLUSION: The most common
polymorphisms in the GABRR genes seemed to be not associated with the risk for
migraine in Caucasian Spanish people, although one of them (GABRR1 rs1186902)
shows a statistically significant association with the age of onset of migraine.
PMID- 28699328
TI - Forecasting Individual Headache Attacks Using Perceived Stress: Development of a
Multivariable Prediction Model for Persons With Episodic Migraine.
AB - OBJECTIVE: To develop and validate a prediction model that forecasts future
migraine attacks for an individual headache sufferer. BACKGROUND: Many headache
patients and physicians believe that precipitants of headache can be identified
and avoided or managed to reduce the frequency of headache attacks. Of the
numerous candidate triggers, perceived stress has received considerable attention
for its association with the onset of headache in episodic and chronic headache
sufferers. However, no evidence is available to support forecasting headache
attacks within individuals using any of the candidate headache triggers. METHODS:
This longitudinal cohort with forecasting model development study enrolled 100
participants with episodic migraine with or without aura, and N = 95 contributed
4626 days of electronic diary data and were included in the analysis. Individual
headache forecasts were derived from current headache state and current levels of
stress using several aspects of the Daily Stress Inventory, a measure of daily
hassles that is completed at the end of each day. The primary outcome measure was
the presence/absence of any headache attack (head pain > 0 on a numerical rating
scale of 0-10) over the next 24 h period. RESULTS: After removing missing data (n
= 431 days), participants in the study experienced a headache attack on 1613/4195
(38.5%) days. A generalized linear mixed-effects forecast model using either the
frequency of stressful events or the perceived intensity of these events fit the
data well. This simple forecasting model possessed promising predictive utility
with an AUC of 0.73 (95% CI 0.71-0.75) in the training sample and an AUC of 0.65
(95% CI 0.6-0.67) in a leave-one-out validation sample. This forecasting model
had a Brier score of 0.202 and possessed good calibration between forecasted
probabilities and observed frequencies but had only low levels of resolution (ie,
sharpness). CONCLUSIONS: This study demonstrates that future headache attacks can
be forecasted for a diverse group of individuals over time. Future work will
enhance prediction through improvements in the assessment of stress as well as
the development of other candidate domains to use in the models.
PMID- 28699329
TI - A Review of Allodynia Is Associated With Initial and Sustained Response to Acute
Migraine Treatment: Results From the American Migraine Prevalence and Prevention
Study.
PMID- 28699330
TI - Stabbing Headache as the Presenting Symptom of Idiopathic Intracranial
Hypertension.
PMID- 28699331
TI - Why Migraine Forecasting Matters.
PMID- 28699332
TI - Prevalence of Restless Legs Syndrome in Migraine Patients: A Case-Control Study.
Analysis of Risk Factors for Restless Legs Syndrome in Migraine Patients.
AB - BACKGROUND: Restless legs syndrome (RLS) is a sensorimotor disorder. It can be
idiopathic, associated to other diseases or to pharmacologic treatments. RLS has
been reported to occur more frequently in migraine patients, but a clear
pathogenetic link seems still under debate. We aimed to evaluate RLS prevalence
in migraine, impact on sleep quality and the main clinical determinants of this
association. METHODS: Migraine patients and age- and sex-matched controls were
enrolled from 1st January 2011 to 30th December 2012. Migraine and RLS diagnosis
complied with already published clinical criteria. Medical and pharmacological
histories, as well as structured questionnaires were collected. RESULTS: RLS was
found in 29/180 (16.1%) patients and 11/180 (6.1%) controls. The odds ratio (OR)
for RLS was 2.95 (CI 95%, 1.42-6.11). Among migraine patients, after adjustment
for possible confounding factors, familial history (OR 3.863, CI 1.076-13.873),
and serotoninergic overload (OR 3.654, CI 1.347-9.916) were significantly
associated with RLS occurrence. Pittsburgh Sleep Quality Index score was higher
in migraine patients with RLS than in subjects without RLS. CONCLUSIONS: The
confirmed association between migraine and RLS might be because of familial
predisposition and to serotoninergic drugs effect, possibly interfering with the
balance between dopaminergic and serotoninergic pathways.
PMID- 28699334
TI - Characterizing cross-subject spatial interaction patterns in functional magnetic
resonance imaging studies: A two-stage point-process model.
AB - We develop a two-stage spatial point process model that introduces new
characterizations of activation patterns in multisubject functional Magnetic
Resonance Imaging (fMRI) studies. Conventionally multisubject fMRI methods rely
on combining information across subjects one voxel at a time in order to identify
locations of peak activation in the brain. The two-stage model that we develop
here addresses shortcomings of standard methods by explicitly modeling the
spatial structure of functional signals and recognizing that corresponding cross
subject functional signals can be spatially misaligned. In our first stage
analysis, we introduce a marked spatial point process model that captures the
spatial features of the functional response and identifies a configuration of
activation units for each subject. The locations of these activation units are
used as input for the second stage model. The point process model of the second
stage analysis is developed to characterize multisubject activation patterns by
estimating the strength of cross-subject interactions at different spatial
ranges. The model uses spatial neighborhoods to account for the cross-subject
spatial misalignment in corresponding functional units. We applied our methods to
an fMRI study of 21 individuals who performed an attention test. We identified
four brain regions that are involved in the test and found that our model results
agree well with our understanding of how these regions engage with the tasks
performed during the attention test. Our results highlighted that cross-subject
interactions are stronger in brain areas that have a more specific function in
performing the experimental tasks than in other areas.
PMID- 28699335
TI - Prevalence of methicillin resistant Staphylococcus aureus (MRSA) bacteremia at
Teaching Hospital Anuradhapura, Sri Lanka
PMID- 28699336
TI - A pilot study on CYP21 gene deletions among a cohort of Sri Lankan children with
congenital adrenal hyperplasia
PMID- 28699337
TI - BK virus vireamia and viruria among a group of post kidney transplant patients in
Sri Lanka
PMID- 28699338
TI - Pre and post operative assessment of voice changes in patients undergoing total
thyroidectomy
PMID- 28699339
TI - Catalyst Controlled Regiodivergent Arylboration of Dienes.
AB - A method for the regiodivergent arylboration of dienes is presented. These
reactions allow for the formation of a diverse range of synthetically versatile
products from simple precursors. Through mechanistic studies, these reactions
likely operate by initial addition of a Cu-Bpin complex across the diene followed
by Pd-catalyzed cross coupling with an aryl halide or pseudohalide.
PMID- 28699340
TI - Overcoming Pitfalls in Boundary Elements Calculations with Computer Simulations
of Ion Selective Membrane Electrodes.
AB - Finite difference analysis of ion-selective membranes is a valuable tool for
understanding a range of time dependent phenomena such as response times, long
and medium term potential drifts, determination of selectivity, and
(re)conditioning kinetics. It is here shown that an established approach based on
the diffusion layer model applied to an ion-exchange membrane fails to use mass
transport to account for concentration changes at the membrane side of the phase
boundary. Instead, such concentrations are imposed by the ion-exchange
equilibrium condition, without taking into account the source of these ions. The
limitation is illustrated with a super-Nernstian potential jump, where a membrane
initially void of analyte ion is exposed to incremental concentrations of analyte
in the sample. To overcome this limitation, the two boundary elements, one at
either side of the sample-membrane interface, are treated here as a combined
entity and its total concentration change is dictated by diffusional fluxes into
and out of the interface. For each time step, the concentration distribution
between the two boundary elements is then computed by ion-exchange theory. The
resulting finite difference simulation is much more robust than the earlier model
and gives a good correlation to experiments.
PMID- 28699341
TI - Six-Step Total Synthesis of Azaspirene.
AB - The total synthesis of (+/-)-azaspirene (1) was achieved in a total of six steps
from commercially available materials. Keys to the conciseness of our synthetic
approach were the effective gamma-lactam formation from linear precursor 36 and
successful tandem epoxidations of gamma-lactam 34 to afford alpha,beta-epoxy
gamma-hydroxy-gamma-lactam intermediate 14. While our streamlined synthesis of
azaspirene (1) sought inspiration from its biogenetic hypothesis, experimentally
observed chemical reactivity of biosynthetically relevant precursors conversely
provides insights to the biological origin of this natural product.
PMID- 28699342
TI - Synthesis of Allene Substituted Nipecotic Acids by Allenylation of Terminal
Alkynes.
AB - The relative reactivities of several secondary amines serving as hydride donors
in propargylic amines undergoing a [1,5]-hydride transfer reaction to yield the
respective terminal and 1,3-disubstituted allenes were studied. For this study, a
two-step procedure was employed. At first, the synthesis of propargylic amines
via the CuI-catalyzed aldehyde-alkyne-amine reactions (A3 coupling) was
accomplished. The obtained propargylic amines were subsequently transformed to
the desired allenes under CdI2 or ZnI2 catalysis. As a result, among the various
secondary amines employed, differing in steric bulk, electronic nature, and
conformational properties, allyl(tert-butyl)amine was found to be the best
hydride donor for the synthesis of terminal allenes. For the synthesis of 1,3
disubstituted allenes, the propyne derivatives containing either a allyl(tert
butyl)amine or a 1,2,3,6-tetrahydropyridine unit in propargylic position
performed best. Finally, with the developed procedure, nipecotic acid derivatives
containing an N-allenyl substituent were synthesized with good yields using
either ZnI2 as catalyst for the preparation of 1-substituted or CdI2 for the
synthesis of 1,3-disubstitued allenes.
PMID- 28699343
TI - Characterization of Adipogenic Activity of House Dust Extracts and Semi-Volatile
Indoor Contaminants in 3T3-L1 Cells.
AB - Obesity and metabolic disorders are of great societal concern and generate
significant human health care costs. Recently, attention has focused on the
potential for environmental contaminants to act as metabolic disruptors. This
study sought to evaluate the adipogenic activity of indoor house dust extracts
and a suite of semivolatile organic chemicals (SVOCs) that are often ubiquitously
detected in indoor environments. 3T3-L1 cells were exposed to extracts of indoor
dust or individual SVOCs and assessed for triglyceride accumulation and
preadipocyte proliferation. Ten of 11 house dust extracts exhibited significant
triglyceride accumulation and/or proliferation at environmentally relevant levels
(<20 MUg of dust/well), and significant adipogenic activity was also exhibited by
28 of the SVOCs. Notably, pyraclostrobin, dibutyl phthalate, tert-butyl-phenyl
diphenyl phosphate, and the isopropylated triaryl phosphates (ITPs) exhibited
near maximal or supra-maximal triglyceride accumulation relative to the
rosiglitazone-induced maximum. The adipogenic activity in house dust occurred at
concentrations below EPA estimated child exposure levels, and raises concerns for
human health impacts, particularly in children. Our results delineate a novel
potential health threat and identify putative causative SVOCs that are likely
contributing to this activity.
PMID- 28699344
TI - Watershed-Scale Impacts from Surface Water Disposal of Oil and Gas Wastewater in
Western Pennsylvania.
AB - Combining horizontal drilling with high volume hydraulic fracturing has increased
extraction of hydrocarbons from low-permeability oil and gas (O&G) formations
across the United States; accompanied by increased wastewater production. Surface
water discharges of O&G wastewater by centralized waste treatment (CWT) plants
pose risks to aquatic and human health. We evaluated the impact of surface water
disposal of O&G wastewater from CWT plants upstream of the Conemaugh River Lake
(dam controlled reservoir) in western Pennsylvania. Regulatory compliance data
were collected to calculate annual contaminant loads (Ba, Cl, total dissolved
solids (TDS)) to document historical industrial activity. In this study, two CWT
plants 10 and 19 km upstream of a reservoir left geochemical signatures in
sediments and porewaters corresponding to peak industrial activity that occurred
5 to 10 years earlier. Sediment cores were sectioned for the collection of paired
samples of sediment and porewater, and analyzed for analytes to identify
unconventional O&G wastewater disposal. Sediment layers corresponding to the
years of maximum O&G wastewater disposal contained higher concentrations of
salts, alkaline earth metals, and organic chemicals. Isotopic ratios of
226Ra/228Ra and 87Sr/86Sr identified that peak concentrations of Ra and Sr were
likely sourced from wastewaters that originated from the Marcellus Shale
formation.
PMID- 28699345
TI - Nanostructural Tailoring to Induce Flexibility in Thermoelectric Ca3Co4O9 Thin
Films.
AB - Because of their inherent rigidity and brittleness, inorganic materials have seen
limited use in flexible thermoelectric applications. On the other hand, for high
output power density and stability, the use of inorganic materials is required.
Here, we demonstrate a concept of fully inorganic flexible thermoelectric thin
films with Ca3Co4O9-on-mica. Ca3Co4O9 is promising not only because of its high
Seebeck coefficient and good electrical conductivity but also because of the
abundance, low cost, and nontoxicity of its constituent raw materials. We show a
promising nanostructural tailoring approach to induce flexibility in inorganic
thin-film materials, achieving flexibility in nanostructured Ca3Co4O9 thin films.
The films were grown by thermally induced phase transformation from CaO-CoO thin
films deposited by reactive rf-magnetron cosputtering from metallic targets of Ca
and Co to the final phase of Ca3Co4O9 on a mica substrate. The pattern of
nanostructural evolution during the solid-state phase transformation is
determined by the surface energy and strain energy contributions, whereas
different distributions of CaO and CoO phases in the as-deposited films promote
different nanostructuring during the phase transformation. Another interesting
fact is that the Ca3Co4O9 film is transferable onto an arbitrary flexible
platform from the parent mica substrate by etch-free dry transfer. The highest
thermoelectric power factor obtained is above 1 * 10-4 W m-1 K-2 in a wide
temperature range, thus showing low-temperature applicability of this class of
materials.
PMID- 28699346
TI - Probing the Morphology and Evolving Dynamics of 3D Printed Nanostructures Using
High-Speed Atomic Force Microscopy.
AB - Focused electron beam induced deposition (FEBID) has been demonstrated as a
promising solution for synthesizing truly three-dimensional (3D) nanostructures.
However, the lack of morphological feedback during growth complicates further
development toward higher spatial fabrication precision. Here, we show that by
combining in situ high speed atomic force microscopy (HS-AFM) with FEBID,
morphologies in multistep fabrication process can be accessed. More importantly,
the proposed method enables simultaneous imaging and fabrication operation, which
opens new possibilities to investigate evolving mechanical properties of the
deposit. The experiments indicate an exponential increase law of the mechanical
resistance, meaning that a mechanically stable state establishes around 4 min
after deposition.
PMID- 28699347
TI - Modular Route to Azaindanes.
AB - A convergent radical based route to azaindanes is described, relying on the
degenerative addition transfer of various substituted S-(pyridylmethyl)-O-ethyl
dithiocarbonates (xanthates) to functional alkenes followed by radical
cyclization onto the pyridine ring activated by protonation with trifluoroacetic
acid. In one case, a richly decorated cyclohepta[b]pyridine could be assembled
swiftly by allowing the first adduct to N-phenylmaleimide to undergo addition to
N-allylphthalimide prior to cyclization.
PMID- 28699348
TI - Impact of the Long-Range Interaction on the Efficiency of the Li + ClH -> LiCl +
H Reaction.
AB - Quantum and quasiclassical calculations have been performed to compute the low
energy efficiency of the Li + ClH -> LiCl + H reaction on some potential energy
surfaces fitted to ab initio electronic energies using different functional
forms. The outcomes of the calculations show marked differences at threshold and
in the shape of the excitation function in seeming contrast with the height of
the saddle to reaction and the width of the cone of acceptance. The differences
in the computed reactive probability and cross section are rationalized in terms
of the attractive/repulsive nature of the long-range interaction and the
inability of trajectory techniques to deal with threshold effects. The vestiges
of these features in the value of the thermal rate coefficients are also
commented on.
PMID- 28699349
TI - Synthesis of Oxatricyclooctanes via Photoinduced Intramolecular Oxa-[4+2]
Cycloaddition of Substituted o-Divinylbenzenes.
AB - The photolysis of substituted o-divinylbenzenes promotes a one-step and metal
free conversion to oxatricycles at room temperature. Irradiation o
divinylbenzenes results in an pericyclic reaction to form cyclic o-quinodiemthane
intermediates, which subsequently undergo intramolecular oxa-[4+2] cycloaddition
to form oxacyclic derivatives.
PMID- 28699350
TI - Analgesic Properties of Opioid/NK1 Multitarget Ligands with Distinct in Vitro
Profiles in Naive and Chronic Constriction Injury Mice.
AB - The lower efficacy of opioids in neuropathic pain may be due to the increased
activity of pronociceptive systems such as substance P. We present evidence to
support this hypothesis in this work from the spinal cord in a neuropathic pain
model in mice. Biochemical analysis confirmed the elevated mRNA and protein level
of pronociceptive substance P, the major endogenous ligand of the neurokinin-1
(NK1) receptor, in the lumbar spinal cord of chronic constriction injury (CCI)
mice. To improve opioid efficacy in neuropathic pain, novel compounds containing
opioid agonist and neurokinin 1 (NK1) receptor antagonist pharmacophores were
designed. Structure-activity studies were performed on opioid agonist/NK1
receptor antagonist hybrid peptides by modification of the C-terminal amide
substituents. All compounds were evaluated for their affinity and in vitro
activity at the mu opioid (MOP) and delta opioid (DOP) receptors, and for their
affinity and antagonist activity at the NK1 receptor. On the basis of their in
vitro profiles, the analgesic properties of two new bifunctional hybrids were
evaluated in naive and CCI-mice, representing models for acute and neuropathic
pain, respectively. The compounds were administered to the spinal cord by lumbar
puncture. In naive mice, the single pharmacophore opioid parent compounds
provided better analgesic results, as compared to the hybrids (max 70% MPE),
raising the acute pain threshold close to 100% MPE. On the other hand, the opioid
parents gave poor analgesic effects under neuropathic pain conditions, while the
best hybrid delivered robust (close to 100% MPE) and long lasting alleviation of
both tactile and thermal hypersensitivity. The results presented emphasize the
potential of opioid/NK1 hybrids in view of analgesia under nerve injury
conditions.
PMID- 28699351
TI - Ultrahypofractionated CyberKnifeTM based stereotactic radiotherapy versus
conventional radiotherapy in patients with prostate cancer - acute toxicity
evaluation in two phase II prospective studies.
AB - Our purpose was to compare the acute toxicity of ultrahypofractionated
CyberKnifeTM based stereotactic radiotherapy (SBRT Arm) and conventional
radiotherapy (EBRT Arm) in prostate cancer patients. Two-hundred-sixteen men with
prostate cancer were enrolled in our prospective studies. One-hundred and nine
were irradiated using CyberKnife to total dose of 36,25 Gy in 5 fractions. One
hundred and seven were irradiated conventionally to total dose of 76 Gy in 38
fractions. Mean age of patients was 69. Acute genitourinary (GU) and
gastrointestinal (GI) adverse-events were collected. The maximal acute toxicity
EORTC/RTOG score was assumed. A total of 41%, 44%, 12% and 3% of patients
presented grade 0, 1, 2 and 3 acute genitourinary toxicity in SBRT arm,
respectively. A total of 21%, 33%, 43% and 3% of patients demonstrated acute
grade 0, 1, 2 and 3 genitourinary toxicity in EBRT arm. A significant difference
between number of patients with grade 2 GU toxicity was observed (p-0.000) and
between patients without any toxicity (p-0.0017).A significant difference in
frequency of acute GI toxicity between both groups was observed, too. 71% vs. 44%
had no toxicity (p-0.0001), and 3% vs. 18% (p-0.0004) presented grade 2 GI
toxicity in SBRT and EBRT arms respectively.The acute toxicity rates of
fractionated stereotactic radiotherapy is lower compared to conventional
irradiation.
PMID- 28699353
TI - Radiation Hormesis: The Link to Nanomolar Hydrogen Peroxide.
AB - Hydrogen peroxide (H2O2) is a stable product of water radiolysis, occurring at
nanomolar concentration upon low-dose ionizing radiation (LDIR) (<100 mGy). In
view of the recent recognition of H2O2 as a central redox signaling molecule
that, likewise, is maintained in the nanomolar range in cells, we propose a role
for H2O2 in radiation hormesis. LDIR is capable of utilizing known molecular
redox master switches such as Nrf2/Keap1 or NF-kappaB/IkappaB to effect adaptive
resistance. This leads to the hypothesis that, as a normal component of the
exposome, LDIR mediates hormetic effects by H2O2 signaling. Antioxid. Redox
Signal. 27, 596-598.
PMID- 28699354
TI - Drug-Mediated Intracellular Donation of Nitric Oxide Potently Inhibits 5
Lipoxygenase: A Possible Key to Future Antileukotriene Therapy.
AB - AIMS: 5-Lipoxygenase (5-LO) is the key enzyme of leukotriene (LT) biosynthesis
and is critically involved in a number of inflammatory diseases such as
arthritis, gout, bronchial asthma, atherosclerosis, and cancer. Because 5-LO
contains critical nucleophilic amino acids, which are sensitive to electrophilic
modifications, we determined the consequences of a drug-mediated intracellular
release of nitric oxide (NO) on 5-LO product formation by human granulocytes and
on 5-LO-dependent pulmonary inflammation in vivo. RESULTS: Clinically relevant
concentrations of NO-releasing nonsteroidal anti-inflammatory drugs and other
agents releasing NO intracellularly suppress 5-LO product synthesis in isolated
human granulocytes via direct S-nitrosylation of 5-LO at the catalytically
important cysteines 416 and 418. Furthermore, suppression of 5-LO product
formation was observed in ionophore-stimulated human whole blood and in an animal
model of pulmonary inflammation. INNOVATION: Here, we report for the first time
that drugs releasing NO intracellularly are efficient 5-LO inhibitors in vitro
and in vivo at least equivalent to approved 5-LO inhibitors. CONCLUSION: Our
findings provide a novel mechanistic strategy for the development of a new class
of drugs suppressing LT biosynthesis by site-directed nitrosylation. The results
may also help to better understand the well-recognized anti-inflammatory
clinically relevant actions of NO-releasing drugs. Furthermore, our study
describes in detail a novel molecular mode of action of NO. Rebound Track: This
work was rejected during standard peer review and rescued by Rebound Peer Review
(Antioxid Redox Signal 16: 293-296, 2012) with the following serving as open
reviewers: Angel Lanas, Hartmut Kuhn, Joan Claria, Orina Belton. Antioxid. Redox
Signal. 28, 1265-1285.
PMID- 28699352
TI - Redox Signaling in Diabetic Wound Healing Regulates Extracellular Matrix
Deposition.
AB - SIGNIFICANCE: Impaired wound healing is a major complication of diabetes, and can
lead to development of chronic foot ulcers in a significant number of patients.
Despite the danger posed by poor healing, very few specific therapies exist,
leaving patients at risk of hospitalization, amputation, and further decline in
overall health. Recent Advances: Redox signaling is a key regulator of wound
healing, especially through its influence on the extracellular matrix (ECM).
Normal redox signaling is disrupted in diabetes leading to several pathological
mechanisms that alter the balance between reactive oxygen species (ROS)
generation and scavenging. Importantly, pathological oxidative stress can alter
ECM structure and function. CRITICAL ISSUES: There is limited understanding of
the specific role of altered redox signaling in the diabetic wound, although
there is evidence that ROS are involved in the underlying pathology. FUTURE
DIRECTIONS: Preclinical studies of antioxidant-based therapies for diabetic wound
healing have yielded promising results. Redox-based therapeutics constitute a
novel approach for the treatment of wounds in diabetes patients that deserve
further investigation. Antioxid. Redox Signal. 27, 823-838.
PMID- 28699355
TI - Content Relevance of the Foot and Ankle Ability Measure in Patients With Achilles
Tendon Diseases.
AB - BACKGROUND: The Foot and Ankle Ability Measure (FAAM) is among the most widely
utilized and best psychometrically supported lower extremity-specific patient
reported outcome measures. However, its content relevance has never been directly
subjected to patient assessment. METHODS: This was an institutional review board
approved, prospective, cross-sectional study of 75 patients with Achilles tendon
diseases who ranked the relevance of the FAAM's items and subscales as 1 = Not
relevant, 2 = Somewhat relevant, or 3 = Very relevant. Substantial content
relevance was indicated by a minimum mean item or subscale score of 2.0.
Nonsurgical and surgical subgroups were compared. RESULTS: At the whole group
level, the mean score was above 2.0 for each individual item and subscale.
Subgroup analysis revealed that the mean relevance was above 2.0 for each of the
items and subscales with the exception of the "Personal Care" item, which
nonsurgical patients ranked significantly lower than did surgical patients (mean
= 1.74 vs 2.23, P = .02). Additionally, this was part of a general trend across
items with more 95% confidence intervals crossing below 2.0 in the nonsurgical
data set (15 items, 52%) than the surgical data set (1 item, 3%). CONCLUSION:
These data confirm that the FAAM has substantial content relevance to patients
with Achilles tendon diseases. However, it is unclear why the surgical subgroup
consistently ranked items higher than did the nonsurgical subgroup. Future work
should address how a patient's content relevance perception is influenced by the
relative effects of their Achilles disease type and their perceived level of
disease-related functional impairment. LEVELS OF EVIDENCE: Diagnostic, Level III.
PMID- 28699356
TI - A Kinect-based movement assessment system: marker position comparison to Vicon.
AB - Accurate movement analysis systems are prohibitive in cost and size to be
accessible to the general population, while commercially available, affordable
systems lack the accuracy needed for clinical relevance. To address these
limitations, we developed a Depth Camera Movement Assessment System (DCMAS)
featuring an affordable, widely available depth camera (e.g. Microsoft Kinect).
After examining 3D position data for markers adhered to participants and a flat
surface, captured with both DCMAS and the industry standard Vicon system, we
demonstrated DCMAS obtained measurements comparable, within soft tissue artifact,
to the Vicon system, paving the way for a breakthrough technology in preventative
medicine.
PMID- 28699357
TI - Adoption of Robot-Assisted Partial Nephrectomies: A Population-Based Analysis of
U.S. Surgeons from 2004 to 2013.
AB - INTRODUCTION: Urological surgeries have contributed to the increasing prevalence
of minimally invasive robotic procedures. Although factors influencing the
adoption of robot-assisted radical prostatectomy have previously been identified,
the explanation for the rapid rise in robotic partial nephrectomies remains
unknown. Using a retrospective population-based sample, we attempt to determine
hospital and surgeon-specific factors influencing a surgeon's decision to utilize
robotic assistance for partial nephrectomies. MATERIALS AND METHODS: A nationally
representative weighted sample of all men who underwent a partial nephrectomy in
the United States between 2003 and 2014 was identified within the Premier
Hospital Database. Hospital, surgeon, and patient characteristics for each
operation were analyzed. Descriptive statistics and a multivariate regression
model stratified according to the Law of Diffusion of Innovation were performed.
RESULTS: A weighted sample of 14,890 nephrectomies was included in the study.
Patient demographics were similar between the two groups. The adoption of robotic
technology followed the Law of Diffusion of Innovation with the percentage of
partial nephrectomies with robotic assistance increasing yearly, reaching 64.1%
by 2013. Surgical volume was a significant factor driving the use of robotic
assistance, with high volume surgeons (>5 partial nephrectomies/year) performing
23.2% more robotic partial nephrectomies per year than their low volume
colleagues (< = 5 partial nephrectomies/year) from 2009 to 2013 (p < 0.001).
CONCLUSIONS: This retrospective population-based study examines key factors
influencing the diffusion of robotic technology for partial nephrectomies.
Surgical volume and year of surgery were found to be the most significant factor
in robotic adoption, with other patient and hospital-specific characteristics
playing a minor role. Future studies are needed to correlate adoption rates with
the clinical or cost-effectiveness of novel technologies within the medical field
to determine whether rapid adoption is a patient-centered vs a clinician-centered
decision point.
PMID- 28699358
TI - Plasma and Urinary Oxytocin Trajectories in Extremely Premature Infants During
NICU Hospitalization.
AB - Extremely premature infants are at great risk for poor neurodevelopmental
outcomes, in part because neurologic structures designed to mature in the womb
must now do so in the extrauterine environment. Reliable biomarkers of
neurodevelopment are especially critical in this population, as behavioral
measures can be unreliable due to immaturity of the premature infant nervous
system. Oxytocin (OT) has the potential to be a marker of neurobiological
processes that offer infant neuroprotection. However, no studies have measured OT
in the plasma and urine of premature infants. The purposes of this study were to
describe plasma and urine OT levels of premature infants through 34 weeks
corrected gestational age (CGA), determine whether plasma and urine OT are
correlated, and explore associations between infant demographics and OT
trajectories. Plasma and urine from 37 premature infants, born at gestational
ages 25-28 6/7 weeks, were longitudinally collected at 14 days of life, then
weekly until 34 weeks CGA. Plasma OT decreased with age, at a rate of 15% per
week, and exhibited strong stability within infants. Urine OT was not correlated
with plasma OT and did not show a significant trend over time; thus, urine may
not be a reliable, noninvasive measurement in this population. Apgar score was
the only infant demographic characteristic associated with plasma OT. Given the
novelty of this work, replication is needed to confirm these findings, and future
research should explore potential mechanisms (e.g., stress, normal maturation,
and social experiences) that contribute to declining plasma OT levels in
premature infants.
PMID- 28699359
TI - Mitochondrial Uptake and Accumulation of Vitamin C: What Can We Learn from Cell
Culture Studies?
AB - SIGNIFICANCE: The mitochondrial fraction of l-ascorbic acid (AA) is of critical
importance for the regulation of the redox status of these organelles and for
cell survival. Recent Advances: Most cell types take up AA by the high-affinity
sodium-dependent vitamin C transporter 2 (SVCT2) sensitive to inhibition by
dehydroascorbic acid (DHA). DHA can also be taken up by glucose transporters
(GLUTs) and then reduced back to AA. DHA concentrations, normally very low in
biological fluids, may only become significant next to superoxide-releasing
cells. Very little is known about the mechanisms mediating the mitochondrial
transport of the vitamin. CRITICAL ISSUES: Information on AA transport is largely
derived from studies using cultured cells and is therefore conditioned by
possible cell culture effects as overexpression of SVCT2 in the plasma membrane
and mitochondria. Mitochondrial SVCT2 is susceptible to inhibition by DHA and
transports AA with a low affinity as a consequence of the restrictive ionic
conditions. In some cells, however, high-affinity mitochondrial transport of AA
is observed. Mitochondrial uptake of DHA may take place through GLUTs, an event
followed by its prompt reduction to AA in the matrix. Intracellular levels of DHA
are, however, normally very low. FUTURE DIRECTIONS: We need to establish, or rule
out, the role and significance of mitochondrial SVCT2 in vivo. The key question
for mitochondrial DHA transport is instead related to its very low intracellular
concentrations.
PMID- 28699361
TI - Long Noncoding RNAs and Cardiac Disease.
AB - SIGNIFICANCE: To maintain homeostasis, gene expression has to be tightly
regulated by complex and multiple mechanisms occurring at the epigenetic,
transcriptional, and post-transcriptional levels. One crucial regulatory
component is represented by long noncoding RNAs (lncRNAs), nonprotein-coding RNA
species implicated in all of these levels. Thus, lncRNAs have been associated
with any given process or pathway of interest in a variety of systems, including
the heart. Recent Advances: Mounting evidence implicates lncRNAs in
cardiovascular diseases (CVD) and progression and their presence in the blood of
heart disease patients indicates that they are attractive potential biomarkers.
CRITICAL ISSUES: Our understanding of the regulation and molecular mechanisms of
action of most lncRNAs remains rudimentary. A challenge is represented by their
often low evolutionary sequence conservation that limits the use of animal models
for preclinical studies. Nevertheless, a growing number of lncRNAs with an impact
on heart function is rapidly accumulating. In this study, we will discuss (i)
lncRNAs that control heart homeostasis and disease; (ii) concepts, approaches,
and methodologies necessary to study lncRNAs in the heart; and (iii) challenges
posed and opportunities presented by lncRNAs as potential therapeutic targets and
biomarkers. FUTURE DIRECTIONS: A deeper knowledge of the molecular mechanisms
underpinning CVDs is necessary to develop more effective treatments. Further
studies are needed to clarify the regulation and function of lncRNAs in the heart
before they can be considered as therapeutic targets and disease biomarkers.
Antioxid. Redox Signal. 29, 880-901.
PMID- 28699360
TI - miR-34a and miR-9 are overexpressed and SIRT genes are downregulated in
peripheral blood mononuclear cells of aging humans.
AB - Increased expression of sirtuins lowers the risk of age-related diseases, while
their role in the regulation of longevity is not firmly established. Since aging
is associated with immunosenescence, we tested whether sirtuin expression was
modified in peripheral blood mononuclear cells (PBMC) in an age-related manner
and whether this might result from altered expression of the selected miRNAs. The
expression of seven SIRT genes and of SIRT1 mRNA-interacting miR-9, miR-34a, miR
132, and miR-199a-5p was evaluated by real-time PCR in PBMC originating from
young (Y, n = 57, mean age 27 +/- 4.3 years), elderly (E, n = 52, 65 +/- 3.4
years), and long-lived (L, n = 56, 94 +/- 3.5 years) individuals. Older age was
associated with a decreased expression of the majority of the SIRT genes. Most
severely affected were median expressions of SIRT1 ( P = 0.000001 for the whole
studied group, Y vs. E: P < 0.000001, Y vs. L: P < 0.000001), and of SIRT3 ( P =
0.000001, Y vs. E: P = 0.000004, Y vs. L: P = 0.000028). Older age was also
associated with the increased median expression of miR-34a ( P = 0.000001, Y vs.
E: P = 0.001, Y vs. L: P = 0.000004) and of miR-9 ( P = 0.05, Y vs. L: P =
0.054). In functional studies, miR-9 interacted with the 3'UTR of SIRT1 mRNA. The
SIRT1 mRNA level negatively correlated with the expression of miR-34a ( r =
0.234, P = 0.003). In conclusion, age-related decrease of SIRT1 expression in
PBMC might in part result from overexpression of miR-34a and miR-9. In addition,
the sustained expression of the SIRT genes in PBMC is not a prerequisite to
longevity in humans but might be one of the reasons for the immune system
dysfunction in the elderly. Impact statement High expression of sirtuins,
particularly SIRT1, lowers the risk of age-related diseases and probably slows
down the rate of aging; therefore, their sustained expression should be one of
the features of longevity. However, in this work we show that in peripheral blood
mononuclear cells (PBMC) of long-lived individuals, expression of majority of the
SIRT genes is significantly lower than in cells of young study subjects. In long
lived individuals, downregulation of SIRT1 coexists with upregulation of SIRT1
mRNA-interacting miR-34a and miR-9, indicating the role of epigenetic drift in
age-dependent deregulation of SIRT1 expression. Such constellation of SIRT1, miR
34a, and miR-9 expression in PBMC of successfully aging long-lived individuals
indicates that, at least in these individuals, it is not a risk factor for
morbidity and mortality. It might however affect the function of the immune
system and, therefore, aging individuals can profit from interventions increasing
the level of SIRT1.
PMID- 28699362
TI - Elevated levels of granzyme B correlated with miR-874-3p downregulation in
patients with acute myocardial infarction.
AB - AIM: Granzyme B could induce apoptosis of target cell in acute myocardial
infarction (AMI) and was identified as the target of miR-874-3p by searching the
miRNA database. We aim to determine the levels of granzyme B and miR-874-3p as
well as assay their correlations or predict powers in AMI. PATIENTS & METHODS: We
measured levels of plasma granzyme B and miR-874-3p in 80 AMI patients or 40
healthy controls and assayed their correlations or predicted powers for AMI.
RESULTS: Elevated levels of granzyme B (16.71 +/- 7.23 ng/l vs 9.27 +/- 3.90
ng/l) correlated with miR-874-3p downregulation (0.20- +/- 0.17-fold vs 1.00- +/-
0.79-fold) in AMI patients. CONCLUSION: Plasma miR-874-3p might target granzyme B
and it might be an additional biomarker for AMI.
PMID- 28699363
TI - Response to letter: 'Bear tracks hypothesis: from atrial fibrillation to atrial
fibrosis syndrome in stroke risk assessment'.
PMID- 28699364
TI - Assistive technologies to address capabilities of people with dementia: From
research to practice.
AB - Assistive technologies became pervasive and virtually present in all our life
domains. They can be either an enabler or an obstacle leading to social
exclusion. The Fondation Mederic Alzheimer gathered international experts of
dementia care, with backgrounds in biomedical, human and social sciences, to
analyze how assistive technologies can address the capabilities of people with
dementia, on the basis of their needs. Discussion covered the unmet needs of
people with dementia, the domains of daily life activities where assistive
technologies can provide help to people with dementia, the enabling and
empowering impact of technology to improve their safety and wellbeing, barriers
and limits of use, technology assessment, ethical and legal issues. The
capability approach (possible freedom) appears particularly relevant in person
centered dementia care and technology development. The focus is not on the
solution, rather on what the person can do with it: seeing dementia as
disability, with technology as an enabler to promote capabilities of the person,
provides a useful framework for both research and practice. This article
summarizes how these concepts took momentum in professional practice and public
policies in the past 15 years (2000-2015), discusses current issues in the
design, development and economic model of assistive technologies for people with
dementia, and covers how these technologies are being used and assessed.
PMID- 28699365
TI - Activating the Chromatin by Noncoding RNAs.
AB - SIGNIFICANCE: The extent and breadth of transcription have recently been
uncovered and this has revealed an extensive array of noncoding RNAs (ncRNAs).
The biological role and significance of these ncRNAs have been realized and to
date it appears that ncRNAs may have many important regulatory functions. ncRNAs
are multifaceted and they induce a complexity of different types of
transcriptional and posttranscriptional regulation, including gene activation.
Recent Advances: Association of ncRNAs with gene activation is an important
finding. Not only enhancer RNA (eRNA) but other types of ncRNAs, including small
RNA (sRNA), long-noncoding RNA (lncRNA), microRNA (miRNA), and PIWI-associated
RNA (piRNA), have also been implicated in gene activation. Interestingly, they
often coincide with histone modifications that favor an open chromatin. In
addition, these ncRNAs can recruit key factors important for transcription,
including RNA polymerase II. They may directly bind the genomic DNA or act as
scaffolds; alternatively, they may loop the chromatin to enhance transcription.
CRITICAL ISSUES: Although the role of small activating (sa)RNAs has been
considerably studied, the roles of miRNAs and piRNAs in gene activation still
need to be substantiated and issues of specificity require further studies.
FUTURE DIRECTIONS: The ncRNA field is coming out of its infancy and we are
gaining a global picture of the importance of ncRNAs. However, detailed
mechanisms of action of the different ncRNAs are still to be determined. This may
reveal novel ways of transcriptional regulation, which will facilitate our
ability to utilize these regulatory pathways for research and therapeutic
purposes. Antioxid. Redox Signal. 29, 813-831.
PMID- 28699366
TI - Attitudes of nurses and the general public towards euthanasia on individuals with
dementia and cognitive impairment.
AB - Objectives Despite the increasing prevalence of dementia, little is known about
individuals' attitudes towards euthanasia on patients with dementia or cognitive
impairment. Methods Nurses (n = 1003) and representatives of the general public
(n = 2796), recruited via social media and the Finnish Nurses Association,
completed an electronic questionnaire in 2014. Results Euthanasia due to severe
dementia was approved by 54.6% of nurses and 64.4% of the general public.
Depending on the age of the patient, between 50.0% and 54.7% of nurses and
between 58.3% and 60.9% of the general public supported euthanasia on patients
with severe cognitive impairment. Discussion The attitudes towards euthanasia due
to dementia or cognitive impairment are slightly more accepting among the general
public than among nurses. Apart from religiosity, none of the background factors
were found to be reliable predictors of individuals' attitudes. Additional
research is needed to describe the underlying reasons for the attitudes.
PMID- 28699367
TI - A comprehensive review of lysine-specific demethylase 1 and its roles in cancer.
AB - Histone methylation plays a key role in the regulation of chromatin structure,
and its dynamics regulates important cellular processes. The investigation of the
role of alterations in histone methylation in cancer has led to the
identification of histone methyltransferases and demethylases as promising novel
targets for therapy. Lysine-specific demethylase 1(LSD1, also known as KDM1A) is
the first discovered histone lysine demethylase, with the ability to demethylase
H3K4me1/2 and H3K9me1/2 at target loci in a context-dependent manner. LSD1
regulates the balance between self-renewal and differentiation of stem cells, and
is highly expressed in various cancers, playing an important role in
differentiation and self-renewal of tumor cells. In this review, we summarize
recent studies about the LSD1, its role in normal and tumor cells, and the
potential use of small molecule LSD1 inhibitors in therapy.
PMID- 28699368
TI - Impact of Blood Pressure, Lesion Level, and Physical Activity on Aortic
Augmentation Index in Persons with Spinal Cord Injury.
AB - Individuals with chronic spinal cord injury (SCI) are at a heightened risk of
cardiovascular disease (CVD) resulting from autonomic nervous system dysfunction,
physical inactivity, and increased inflammatory processes. Arterial stiffness
(AS) is recognized as an independent risk factor for CVD and, specifically, pulse
wave analysis (PWA) has proven to be a useful tool to predict and track
structural arterial changes that reflect arteriosclerosis. The augmentation index
(AI) can be used to estimate AS and is derived from the amplitude and timing of
the blood pressure (BP) wave reflection in a peripheral artery. Recently, AS has
been shown to be increased in persons with SCI compared with the uninjured
population; however, possible contributors to increased AS in the SCI population
have not been fully explored. In this study, increased radial artery AI is
demonstrated in persons with high cord lesions (above T6) compared with
individuals with low cord lesions (T7 and below) and uninjured controls. The
association between age and AI was not significant in the SCI population;
however, there was a direct association between AI and level of injury. Further,
AI was inversely associated with seated systolic blood pressure (SBP) and was
increased in individuals who reported orthostatic hypotension (OH) and in those
who were physically inactive. In conclusion, individuals with higher cord lesions
have more severe cardiovascular autonomic disruption, leading to orthostatic BP
dysregulation and physical inactivity, which appear to contribute independently
to increased AS in these individuals.
PMID- 28699369
TI - Single-centre experience with intradetrusor injection of onabotulinumtoxinA: a
retrospective study of the years 2003-2012 in a Danish population.
AB - OBJECTIVE: This study aimed to evaluate the efficacy of treatment for
incontinence due to neurogenic detrusor overactivity (NDO) and idiopathic
detrusor overactivity (IDO) with onabotulinumtoxinA (BoNT-A) at Aarhus University
Hospital, Skejby, Denmark. MATERIALS AND METHODS: The data were collected
retrospectively by systematic review of the patient records from March 2003 to
May 2012. Patients treated with BoNT-A over the age of 18 years were included.
Treatment indication, diagnosis, adverse events, treatment interval, duration of
effect and effect grade were registered. Follow-up data were collected by a
telephone interview 4 weeks after treatment. RESULTS: The study identified 219
patients, who received a total of 657 treatments during the period. Full effect
of the treatment was experienced in 71%, intermediate effect was seen in 16% and
low effect in 3%. There was no difference in effect duration between the IDO and
NDO groups. The most common adverse event was the need to perform clean
intermittent self-catheterization; 27% of all patients experienced this. Urinary
tract infections were reported in 5% of procedures and significant haematuria in
1%. These findings correspond with the results of other published studies.
CONCLUSION: BoNT-A is a safe and effective treatment for incontinence in IDO and
NDO.
PMID- 28699370
TI - ADC quantification in basilar artery occlusion as an indicator of clinical
outcome after endovascular treatment.
AB - Background Acute ischemic stroke due to basilar artery occlusion (BAO) is
associated with a dismal prognosis and, even though endovascular treatment (EVT)
contributed to an improvement in clinical outcomes, patient selection is
difficult and frequently results in futile recanalization. We investigated the
prognostic value of baseline ADC quantification in patients with BAO undergoing
EVT. Methods We retrospectively evaluated MRI at admission in 11 patients with
BAO undergoing EVT. Ischemic lesions were defined on baseline DWI and minimum ADC
(minADC), ADC ratio and total area were quantified. Final infarction area was
determined on follow-up T2WI/CT. We assessed the correlation between imaging
parameters, recanalization grade and clinical scores (NIHSS at admission, NIHSS
and mRS at discharge and mRS at three months) using Spearman rank correlation
coefficient and correcting for multiple comparisons with the false discovery rate
(FDR). Results Lower values of minADC at admission MRI are strongly correlated
with higher scores in NIHSS (rs = -0.845, p = 0.001) and mRS at discharge (rs =
0.743, p = 0.009). We also found a negative correlation between minADC and NIHSS
at admission (rs = -0.67, p = 0.02), mRS at three months and difference between
pre- and post-treatment ischemic area (rs = -0.664, p = 0.026) that lost
significance with FDR correction. Ischemic area and TICI grade were not
significantly associated with clinical results. Conclusions ADC quantification of
ischemic lesions at baseline MRI seems to predict clinical outcome in patients
with BAO undergoing EVT, more importantly than ischemic area or TICI grade.
PMID- 28699371
TI - Minocycline Attenuates High Mobility Group Box 1 Translocation, Microglial
Activation, and Thalamic Neurodegeneration after Traumatic Brain Injury in Post
Natal Day 17 Rats.
AB - In response to cell injury, the danger signal high mobility group box-1 (HMGB) is
released, activating macrophages by binding pattern recognition receptors. We
investigated the role of the anti-inflammatory drug minocycline in attenuating
HMGB1 translocation, microglial activation, and neuronal injury in a rat model of
pediatric traumatic brain injury (TBI). Post-natal day 17 Sprague-Dawley rats
underwent moderate-severe controlled cortical impact (CCI). Animals were
randomized to treatment with minocycline (90 mg/kg, intraperitoneally) or vehicle
(saline) at 10 min and 20 h after injury. Shams received anesthesia and
craniotomy. We analyzed HMGB1 translocation (protein fractionation and Western
blotting), microglial activation (Iba-1 immunohistochemistry), neuronal death
(Fluoro-Jade-B [FJB] immunofluorescence), and neuronal cell counts (unbiased
stereology). Behavioral assessments included motor and Morris-water maze testing.
Nuclear to cytosolic translocation of HMGB1 in the injured brain was attenuated
in minocycline versus vehicle-treated rats at 24 h (p < 0.001). Treatment with
minocycline reduced microglial activation in the ipsilateral cortex, hippocampus,
and thalamus (p < 0.05 vs. vehicle, all regions); attenuated neurodegeneration
(FJB-positive neurons) at seven days (p < 0.05 vs. vehicle); and increased
thalamic neuronal survival at 14 days (naive 22773 +/- 1012 cells/mm3, CCI +
vehicle 11753 +/- 464, CCI + minocycline 17047 +/- 524; p < 0.001). Minocycline
treated rats demonstrated delayed motor recovery early after injury but had no
injury effect on Morris-water maze whereas vehicle-treated rats performed worse
than sham on the final two days of testing (both p < 0.05 vs. vehicle).
Minocycline globally attenuated HMGB1 translocation and microglial activation in
injured brain in a pediatric TBI model and afforded selective thalamic
neuroprotection. The HMGB1 translocation and thalamic injury may represent novel
mechanistic and regional therapeutic targets in pediatric TBI.
PMID- 28699372
TI - Hemispheric asymmetries in dorsal language pathway white-matter tracts: A
magnetic resonance imaging tractography and functional magnetic resonance imaging
study.
AB - Introduction Previous studies have shown that the arcuate fasciculus has a
leftward asymmetry in right-handers that could be correlated with the language
lateralisation defined by functional magnetic resonance imaging. Nonetheless,
information about the asymmetry of the other fibres that constitute the dorsal
language pathway is scarce. Objectives This study investigated the asymmetry of
the white-matter tracts involved in the dorsal language pathway through the
diffusion tensor imaging (DTI) technique, in relation to language hemispheric
dominance determined by task-dependent functional magnetic resonance imaging
(fMRI). Methods We selected 11 patients (10 right-handed) who had been studied
with task-dependent fMRI for language areas and DTI and who had no language
impairment or structural abnormalities that could compromise magnetic resonance
tractography of the fibres involved in the dorsal language pathway. Laterality
indices (LI) for fMRI and for the volumes of each tract were calculated. Results
In fMRI, all the right-handers had left hemispheric lateralisation, and the
ambidextrous subject presented right hemispheric dominance. The arcuate
fasciculus LI was strongly correlated with fMRI LI ( r = 0.739, p = 0.009),
presenting the same lateralisation of fMRI in seven subjects (including the right
hemispheric dominant). It was not asymmetric in three cases and had opposite
lateralisation in one case. The other tracts presented predominance for rightward
lateralisation, especially superior longitudinal fasciculus (SLF) II/III (nine
subjects), but their LI did not correlate (directly or inversely) with fMRI LI.
Conclusion The fibres that constitute the dorsal language pathway have an
asymmetric distribution in the cerebral hemispheres. Only the asymmetry of the
arcuate fasciculus is correlated with fMRI language lateralisation.
PMID- 28699373
TI - Recall and patient perceptions of hip precautions 6 weeks after total hip
arthroplasty.
AB - Background and purpose - There is a lack of evidence to support the role of hip
precautions in preventing dislocation following total hip arthroplasty (THA). We
report an exploratory study which assesses recall, adherence, and the impact of
precautions on activities of daily living in the first 6 weeks postoperatively.
Patients and methods - We designed a new questionnaire based on the education
patients receive and refined by professionals within our multidisciplinary team.
129 patients underwent primary elective THA during the study period and received
the questionnaire at 6 weeks postoperatively. Results - 97 (75%) patients
responded before the 8th week postoperatively. Most of these (83 patients) could
remember all the precautions. Of the 97 who responded only 22 claimed to adhere
to all of the precautions. 48 admitted to putting their own underwear on without
the use of aids or assistance, and 38 had started walking without an aid. Due to
the precautions 67 avoided leaving the house at some point and 63 were unable to
perform desired activities. 84 stated that their sleep was affected. There were
no dislocations among the 97 patients who responded; however, there was 1
dislocation among the 32 non-responders. Interpretation - We found that most
patients did not adhere to hip precaution advice. Precautions have a detrimental
effect on patient activity and sleep. In view of the limited efficacy in reducing
dislocation rate, we question the use of precautions in the primary arthroplasty
setting.
PMID- 28699374
TI - Shared medical appointments for managing pain in primary care settings?
PMID- 28699375
TI - Novel Insights into Tat Pathway in Xanthomonas oryzae pv. oryzae Stress Adaption
and Virulence: Identification and Characterization of Tat-Dependent Translocation
Proteins.
AB - Xanthomonas oryzae pv. oryzae, an economically important bacterium, causes a
serious disease in rice production worldwide called bacterial leaf blight. How X.
oryzae pv. oryzae infects rice and causes symptoms remains incompletely
understood. Our earlier works demonstrated that the twin-arginine translocation
(Tat) pathway plays an vital role in X. oryzae pv. oryzae fitness and virulence
but the underlying mechanism is unknown. In this study, we used strain PXO99A as
a working model, and identified 15 potential Tat-dependent translocation proteins
(TDTP) by using comparative proteomics and bioinformatics analyses. Combining
systematic mutagenesis, phenotypic characterization, and gene expression, we
found that multiple TDTP play key roles in X. oryzae pv. oryzae adaption or
virulence. In particular, four TDTP (PXO_02203, PXO_03477, PXO_02523, and
PXO_02951) were involved in virulence, three TDTP (PXO_02203, PXO_03477, and
PXO_02523) contributed to colonization in planta, one TDTP (PXO_02671) had a key
role in attachment to leaf surface, four TDTP (PXO_02523, PXO_02951, PXO_03132,
and PXO_03841) were involved in tolerance to multiple stresses, and two TDTP
(PXO_02523 and PXO_02671) were required for full swarming motility. These
findings suggest that multiple TDTP may have differential contributions to
involvement of the Tat pathway in X. oryzae pv. oryzae adaption, physiology, and
pathogenicity.
PMID- 28699376
TI - Corrigendum.
PMID- 28699377
TI - Microbiological and immunological profile of patients with severe lupus flares
related to bloodstream infections: a retrospective cohort study.
AB - Background This study aimed to address whether bloodstream infections are a risk
factor for the development of severe lupus flares, as well as clinical,
immunological and microbiological features of patients with bloodstream
infections that develop severe lupus flares. Methods We performed a retrospective
cohort study comparing 87 systemic lupus erythematosus (SLE) patients with
bloodstream infections and 87 hospitalized SLE patients without bloodstream
infections as a comparison group. All patients were followed up for at least 3
months or until one of the primary outcomes was developed (severe SLE flare
according to SELENA/SLEDAI score or death). Microbiological features of all
bloodstream infections were recorded. The disease status at the end of follow up
was registered. Results A total of 23 patients (13.2%) developed a severe flare
during follow up; among them, 20 (87%) had an associated episode of bloodstream
infection ( p < 0.001). The most frequent flares were renal (43.4%) and severe
thrombocytopenia (26%). After multivariate analysis, baseline-independent factors
associated with severe SLE flare were bloodstream infection [hazard ratio (HR)
7.3, 95% confidence interval (CI) 2.13-24.95; p = 0.002]. Among patients with
bloodstream infections, low C4 levels (HR 2.43, 95% CI 1.04-5.69: p = 0.04) and
Streptococcus pneumoniae were associated with severe SLE flare (HR 3.41, 95% CI
1.68-6.91; p = 0.012). Conclusions SLE patients with bloodstream infections,
especially due to S. pneumoniae, and low C4 levels, are at higher risk for
development of severe SLE flares.
PMID- 28699378
TI - Reasons for cesarean and medically indicated deliveries in pregnancies in women
with systemic lupus erythematosus.
AB - Objective To determine reasons for cesarean and medically indicated deliveries in
a registry of pregnant women with SLE compared to RA. Methods Pregnant women with
SLE or RA were prospectively followed, and pregnancy outcomes were collected,
including whether labor was spontaneous or medically indicated and delivery was
vaginal or cesarean. Preterm birth was defined as a birth <37 weeks gestation.
Differences in reasons for cesarean delivery and indication of delivery between
term and preterm births were determined by Fisher's exact test. Results Compared
to RA pregnancies, SLE pregnancies had modestly higher rates of preterm birth
(24% SLE vs 14% RA), pre-eclampsia (15% SLE vs 7% RA), and cesarean delivery (48%
SLE vs 30% RA). The majority of preterm births among women with SLE were
indicated (70%), most commonly for pre-eclampsia or the health of the infant or
mother. The majority of preterm births among women with RA, however, were
spontaneous, primarily due to premature rupture of membranes. Conclusion Pre
eclampsia and maternal SLE activity appear to be the key drivers for the high
rate of preterm birth and medically indicated delivery in SLE. This contrasts
with RA, where preterm labor is most often due to spontaneous onset of labor.
PMID- 28699379
TI - What dilemmas do healthcare workers face looking after children with acute pain?
AB - There have been significant advances in the treatment of acute pain in children
alongside increased academic interest in the field. This has led to improvements
in both efficacy and safety alongside the development of multidisciplinary pain
services. Despite this, however, there are still high rates of acute pain
reported in children in both inpatient and outpatient settings. In this article,
we discuss some of the challenges faced by healthcare workers in designing
effective multidisciplinary treatment regimens, understanding the implications
for long-term pain and pain processing of acute pain and analgesic interventions
as well as ongoing issues around research, education and resource.
PMID- 28699380
TI - Addressing the barriers related with opioid therapy for management of chronic
pain in India.
AB - India has a high prevalence of chronic disorders which may be associated with
persistent pain. Despite the availability of multiple treatment options, chronic
pain is largely untreated and contributes to disability and mortality. Medical
consumption of opioids remains low due to various barriers that prevent access to
opioids for patients and healthcare practitioners. Stringent regulatory
provisions outlined in the Narcotic Drugs and Psychotropic Substances Act (1985)
have been major deterrents to adequate opioid use. Although multiple amendments
to the act have ensured ease of opioid access for medicinal purposes, concerns
such as lack of awareness and prescribing practices and attitudes of
physicians/patients still need to be addressed. This review aims to identify
these barriers and suggest recommendations to overcome them.
PMID- 28699381
TI - Prospective Assessment of Acute Blood Markers of Brain Injury in Sport-Related
Concussion.
AB - There is a pressing need to identify objective biomarkers for the assessment of
sport-related concussion (SRC) to reduce the reliance on clinical judgment for
the management of these injuries. The goal of the current study was to
prospectively establish the acute effects of SRC on serum levels of S100 calcium
binding protein beta (S100B), glial fibrillary acidic protein (GFAP), and
ubiquitin C-terminal hydrolase-L1 (UCH-L1). Collegiate and high school football
players were enrolled and provided blood at pre-season. Injured athletes
participated in follow-up visits at ~6 and 24-48 h following documented SRC (n =
32). Uninjured football players participated in similar follow-up visits and
served as controls (n = 29). The median time between injury and blood collection
was 2 h (6 h visit) and 22.5 h (24-48 h visit) in concussed athletes. Concussed
athletes had significantly elevated UCH-L1 levels at the 6 h visit relative to
pre-season levels (Z = 2.22, p = 0.03) and levels in control athletes (Z = 3.02,
p = 0.003). Concussed athletes also had elevated S100B at 6 h relative to pre
season (Z = 2.07, p = 0.04) and controls (Z = 2.75, p = 0.006). Both markers
showed fair discrimination between concussed and control athletes (UCH-L1 area
under receiver operating characteristic curve [AUC] [95% CI] = 0.74 [0.61-0.88],
S100B AUC = 0.72 [0.58-0.87]). Percent-change of UCH-L1 and S100B at 6 h relative
to pre-season also showed fair discrimination (AUC = 0.79 [0.66-0.92] and AUC =
0.77 [0.64-0.90]). GFAP levels did not differ between groups or in concussed
athletes relative to pre-season. This study provides prospective evidence of
significant increases in serum levels of UCH-L1 and S100B during the early acute
period following SRC, and lays the foundation for future studies examining the
clinical potential for blood-based biomarkers in the early detection of
concussion.
PMID- 28699382
TI - An Adaptive Approach to Locating Mobile HIV Testing Services.
AB - BACKGROUND: Public health agencies suggest targeting "hotspots" to identify
individuals with undetected HIV infection. However, definitions of hotspots vary.
Little is known about how best to target mobile HIV testing resources. METHODS:
We conducted a computer-based tournament to compare the yield of 4 algorithms for
mobile HIV testing. Over 180 rounds of play, the algorithms selected 1 of 3
hypothetical zones, each with unknown prevalence of undiagnosed HIV, in which to
conduct a fixed number of HIV tests. The algorithms were: 1) Thompson Sampling,
an adaptive Bayesian search strategy; 2) Explore-then-Exploit, a strategy that
initially draws comparable samples from all zones and then devotes all remaining
rounds of play to HIV testing in whichever zone produced the highest observed
yield; 3) Retrospection, a strategy using only base prevalence information; and;
4) Clairvoyance, a benchmarking strategy that employs perfect information about
HIV prevalence in each zone. RESULTS: Over 250 tournament runs, Thompson Sampling
outperformed Explore-then-Exploit 66% of the time, identifying 15% more cases.
Thompson Sampling's superiority persisted in a variety of circumstances examined
in the sensitivity analysis. Case detection rates using Thompson Sampling were,
on average, within 90% of the benchmark established by Clairvoyance.
Retrospection was consistently the poorest performer. LIMITATIONS: We did not
consider either selection bias (i.e., the correlation between infection status
and the decision to obtain an HIV test) or the costs of relocation to another
zone from one round of play to the next. CONCLUSIONS: Adaptive methods like
Thompson Sampling for mobile HIV testing are practical and effective, and may
have advantages over other commonly used strategies.
PMID- 28699383
TI - Flawed communications: Health professionals' experience of collaboration in the
care of frail elderly patients.
AB - AIMS: Frail elderly patients who have multiple illnesses do not fare well in
modern health care systems, mainly due to a lack of care planning and flawed
communication between health professionals in different care organisations. This
is especially noticeable when patients are discharged from hospital. The aim of
this study was to explore health care professionals' experience of obstacles and
opportunities for collaboration. METHODS: Health professionals were invited to
participate in three focus groups, each consisting of a hospital physician, a
primary care physician, a hospital nurse, a primary care nurse, a municipal home
care nurse or an assistant officer, a physical or occupational therapist and a
patient or a family member representative. These individual people were then
asked to discuss the obstacles and opportunities for communication between
themselves and with the patients and their relatives when presented with the case
report of a fictitious patient. Content analysis was used to identify categories.
RESULTS: Several obstacles were identified for effective communication and care
planning: insufficient communication with patients and relatives; delayed
collaboration between care-givers; the lack of an adequate responsible person for
care planning; and resources not being distributed according to the actual needs
of patients. The absence of an overarching responsibility for the patient, beyond
organisational borders, was a recurring theme. These obstacles could also be seen
as opportunities. CONCLUSIONS: Obstacles for collaboration were found on three
levels: societal, organisational and individual. As health care professionals are
well aware of the problems and also see solutions, management for health care
should support employees' own initiatives for changes that are of benefit in the
care of frail elderly patients with multiple illnesses.
PMID- 28699384
TI - Preclinical Safety Evaluation of Allogeneic Induced Pluripotent Stem Cell-Based
Therapy in a Swine Model of Myocardial Infarction.
AB - The combination of biomatrices and induced pluripotent stem cell (iPSC)
derivatives to aid repair and myocardial scar formation may soon become a reality
for cardiac regenerative medicine. However, the tumor risk associated with
residual undifferentiated cells remains an important safety concern of iPSC-based
therapies. This concern is not satisfactorily addressed in xenotransplantation,
which requires immune suppression of the transplanted animal. In this study, we
assessed the safety of transplanting undifferentiated iPSCs in an allogeneic
setting. Given that swine are commonly used as large animal models in cardiac
medicine, we used porcine iPSCs (p-iPSCs) in conjunction with bioengineered
constructs that support recovery after acute myocardial infarction.
Histopathology analyses found no evidence of p-iPSCs or p-iPSC-derived cells
within the host myocardium or biomatrices after 30 and 90 days of follow-up.
Consistent with the disappearance of the implanted cells, we could not observe
functional benefit of these treatments in terms of left ventricular ejection
fraction, cardiac output, ventricular volumes, or necrosis. We therefore conclude
that residual undifferentiated iPSCs should pose no safety concern when used on
immune-competent recipients in an allogeneic setting, at least in the context of
cardiac regenerative medicine.
PMID- 28699385
TI - Intravaginal practices among young HIV-infected women in Lusaka, Zambia.
AB - Intravaginal practices (IVP) are linked to bacterial vaginosis (BV),
obstetric/gynecological complications, and HIV. Late adolescent and young adult
(LAYA) women in Zambia have high rates of HIV. Adult and mature (AM) HIV-infected
women in Zambia engage in IVP for hygiene, health, and sexuality reasons;
however, to our knowledge, IVP use among LAYA women has not been examined. This
study compares IVP use between LAYA and AM women to identify age-specific factors
to target when developing IVP reduction interventions for LAYA women. LAYA (<=25
years; n = 24) and AM (>25 years; n=124) HIV-infected women completed self
administered demographic, HIV history, sexual risk factor, and IVP measures. LAYA
and AM women were then compared. Number of sexual partners, sexual activity, or
condom use did not differ between groups. Rates of IVP in the prior month with
different products were similar, though LAYA women used soap more frequently (96%
versus 74.2%, p = 0.034). LAYA women were more likely to use products for hygiene
reasons (soap 83% versus 43%; cloth, paper, or wipes 50% versus 17%, p < 0.05);
and AM women to use products to please sexual partners (cloth 20% versus 56%, p =
0.074). Interventions tailored to LAYA women may be needed to reduce IVP and
subsequent BV as LAYA women may have different reasons for engaging in IVP, in
comparison with AM women. Reduced IVP among LAYA women may decrease the risk for
HIV transmission to sexual partners and newborns and is urgently needed in
settings with high prevalence of IVP, BV, and HIV infections, such as Zambia.
PMID- 28699386
TI - Organisational factors and occupational balance in working parents in Sweden.
AB - BACKGROUND: Parents with small children constitute a vulnerable group as they
have an increased risk of sick leave due to stress-related disorders compared to
adults without children. It has been shown that mothers and fathers to small
children together spend more time in paid work than any other group, which could
create negative stress and an experience of low occupational balance. AIM: The
aim of this study was to examine associations between organisational factors and
occupational balance among parents with small children in Sweden. METHODS: Data
were collected by a survey including questions about occupational balance,
organisational factors and age, sex, employment rate, work position, monthly
household income, number of children at home, separation/divorce last five years
and overtime. The total number of parents included in this study was 718 (490
mothers and 228 fathers). Logistic regression models were applied to examine the
odds ratios for occupational balance in relation to organisational factors.
RESULTS: Parents who experienced positive attitudes towards parenthood and
parental leave among colleagues and managers were more likely to experience high
occupational balance than parents who experienced negative or neutral attitudes.
Having a clear structure for handover when absent from work was also strongly
associated with high occupational balance. CONCLUSIONS: The result of the present
study indicates that some organisational factors could be important for the
occupational balance of parents with small children.
PMID- 28699387
TI - Low Power Laser Therapy: A Strategy to Promote the Osteogenic Differentiation of
Deciduous Dental Pulp Stem Cells from Cleft Lip and Palate Patients.
AB - Dental pulp stem cells (DPSCs) can undergo several types of differentiation,
including osteogenic differentiation. One osteogenesis-inducing factor that has
been previously described is in vitro low-power laser irradiation of cells. Laser
irradiation promotes the acceleration of bone matrix mineralization of the cell
strain. However, no consensus exists regarding the dose and treatment time. We
used DPSC strains from cleft lip and palate patients because new bone tissue
engineering strategies have used DPSCs in preclinical and clinical trials for the
rehabilitation of alveolar bone clefts. Optimizing bone tissue engineering
techniques for cleft and lip palate patients by applying low-power laser therapy
(LPLT) to DPSCs obtained from these patients can help improve current strategies
to quickly close large alveolar clefts. The aim of this study was to investigate
the effects of LPLT at different energy densities in DPSC strains obtained from
cleft lip and palate patients during in vitro osteogenic differentiation. Ten
DPSC strains were obtained from cleft lip and palate patients and then used in
the following study groups: group 1: control, the strains underwent osteogenic
differentiation for 21 days; and groups 2, 3, and 4: the strains were irradiated
each day with a low-power red laser (660 nm) (5, 10, and 20 J) during 21 days of
osteogenic differentiation. Using Bonferroni's test, a statistically significant
difference in the mean values was found between the irradiated groups (2, 3, and
4) and the control group (p < 0.001). However, no significant difference in
osteogenic potential was found among the irradiated groups. Our findings showed
that the osteogenic potential of DPSCs increases with red laser irradiation at 5,
10, and 20 J, and this treatment could be considered a new approach for
preconditioning these cells to be used in bone tissue engineering.
PMID- 28699388
TI - Current indications for stentless aortic bioprostheses.
AB - The best aortic prostheses have been debated for decades. The introduction of
stentless aortic bioprostheses was aimed at improving hemodynamics and
potentially the durability of aortic bioprostheses. Despite the good short- and
long-term outcomes after implantation of stentless aortic bioprostheses, their
use remains limited owing to the technically demanding implantation techniques.
Nevertheless, stentless aortic bioprostheses might be of special benefit in
certain indications, where they could be a valuable addition to the surgical
armamentarium.
PMID- 28699389
TI - Anomalous systemic arterialization of the right lower lobe in a septuagenarian.
PMID- 28699390
TI - Randomized controlled trial of chest tube removal aided by a party balloon.
AB - Background Recurrent pneumothorax is one of the most common complications after
thoracostomy tube removal. The purpose of this study was to assess the optimal
method of thoracostomy tube removal by comparing party balloon-assisted Valsalva
and classic Valsalva techniques. Methods Trauma patients with indications for
tube thoracostomy from 2014 to 2015 were recruited. Exclusion criteria were age <
15- or > 64-years-old, history of chronic lung disease, Glasgow Coma Scale < 13,
latex allergy, or tracheostomy. Participants were randomly allocated by
randomized block design into 4 groups using different Valsalva maneuvers: group
A: classic inspired, group B: classic expired, group C: balloon-inspired; and
group D: balloon-expired. The primary and secondary outcomes were recurrent
pneumothorax and respiratory complications. Results Forty-eight tube
thoracostomies were randomized for analysis; 4 patients had bilateral tube
thoracostomies. The mean patient age was 38.1 +/- 19.9 years. The incidence of
recurrent pneumothorax confirmed by chest radiography was 15.4% in group A, 16.8%
in group B, and none in groups C and D ( p = 0.31). When group A combined with
group B was compared with groups C and D, the incidence was 16% vs. 0%,
respectively ( p = 0.11). The thoracostomy tube reinsertion rate in all 4 groups
was 0%, 8.33%, 0%, and 0%, respectively, which was not significant ( p = 0.38).
Conclusions Performing the Valsalva maneuver correctly during full inspiration
may be the method of choice for removing thoracostomy tubes. Using a party
balloon forces the patient perform the Valsalva maneuver adequately and is
simpler to explain.
PMID- 28699391
TI - Anti-PD-1 Antibody Therapy Induces Hashimoto's Disease with an Increase in
Peripheral Blood Follicular Helper T Cells.
PMID- 28699392
TI - Unemployment, precarious employment and health in young people.
PMID- 28699393
TI - Mental health promotion competencies in the health sector in Finland: a
qualitative study of the views of professionals.
AB - AIMS: In this study, we aimed to investigate what competencies are needed for
mental health promotion in health sector practice in Finland. METHODS: A
qualitative study was carried out to seek the views of mental health
professionals regarding mental health promotion-related competencies. The data
were collected via two focus groups and a questionnaire survey of professionals
working in the health sector in Finland. The focus groups consisted of a total of
13 professionals. Further, 20 questionnaires were received from the questionnaire
survey. The data were analysed using the qualitative data analysis software
ATLAS.ti Scientific Software Development GmbH, Berlin. A content analysis was
carried out. RESULTS: In total, 23 competencies were identified and clustered
under the categories of theoretical knowledge, practical skills, and personal
attitudes and values. In order to promote mental health, it is necessary to have
a knowledge of the principles and concepts of mental health promotion, including
methods and tools for effective practices. Furthermore, a variety of skills-based
competencies such as communication and collaboration skills were described.
Personal attitudes and values included a holistic approach and respect for human
rights, among others. CONCLUSIONS: The study provides new information on what
competencies are needed to plan, implement and evaluate mental health promotion
in health sector practice, with the aim of contributing to a more effective
workforce. The competencies provide aid in planning training programmes and
qualifications, as well as job descriptions and roles in health sector workplaces
related to mental health promotion.
PMID- 28699394
TI - Stepping out of the shadows of Alzheimer's disease: a phenomenological
hermeneutic study of older people with Alzheimer's disease caring for a therapy
dog.
AB - PURPOSE: Living with Alzheimer's disease (AD) can involve a person being unable
to recall and convey information in daily life. There are several ways to provide
person-centred care to older people with AD, e.g. by empowering them in a
situation. The use of animal-assisted therapy (AAT) with a therapy dog in the
care of people with dementia is increasing, with the presence of a therapy dog
being described as improving, among other things, the well-being and
socialization of the person. The aim of this study was to illuminate meanings of
care for people with AD in their encounters with a therapy dog. METHOD: The study
used video-recorded observations of the person with AD and the dog. Data were
transcribed and analysed using a phenomenological hermeneutic method. RESULTS:
The main theme was "Using one's own resources and abilities as a human being",
which meant being the person one can be and distancing oneself from the symptoms
of AD during the time with the dog. CONCLUSIONS: The feelings evoked in the
people with AD included empathy and altruism, which allowed for a sense of joy
and tenderness, which may induce a sense of self-worth, of being needed, and of
being meaningful.
PMID- 28699395
TI - Scedosporium apiospermum infection: lethal complication after extracorporeal
cardiopulmonary resuscitation.
AB - In recent years, the development of extracorporeal membrane oxygenation (ECMO)
technology has led to its extensive use in clinical practice. In particular, ECMO
can play an important role in cardiopulmonary resuscitation (CPR). The American
Heart Association CPR guidelines recommend its use in patients with cardiac
arrest due to reversible disorders, along with high-quality CPR. This is called
extracorporeal cardiopulmonary resuscitation (ECPR). However, it is important to
be aware of the possibility of infection-related complications. Here, we report
on a patient who suffered a cardiac arrest in hospital and was rescued with ECMO,
but who subsequently developed an infection with Scedosporium apiospermum.
PMID- 28699396
TI - Validation of the Edinburgh Postnatal Depression Scale (EPDS) on the Thai-Myanmar
border.
AB - Postnatal depression is common and may have severe consequences for women and
their children. Locally validated screening tools are required to identify at
risk women in marginalised populations. The Edinburgh Postnatal Depression Scale
(EPDS) is one of the most frequently used tools globally. This cross-sectional
study assessed the validity and acceptability of the EPDS in Karen and Burmese
among postpartum migrant and refugee women on the Thai-Myanmar border. The EPDS
was administered to participants and results compared with a diagnostic
interview. Local staff provided feedback on the acceptability of the EPDS through
a focus group discussion. Results from 670 women showed high accuracy and
reasonable internal consistency of the EPDS. However, acceptability to local
staff was low, limiting the utility of the EPDS in this setting despite its good
psychometrics. Further work is required to identify a tool that is acceptable and
sensitive to cultural manifestations of depression in this vulnerable population.
PMID- 28699398
TI - Compartment-Specific Importance of Ascorbate During Environmental Stress in
Plants.
AB - SIGNIFICANCE: Ascorbate is an essential antioxidant in plants. Total contents and
its redox state in organelles are crucial to fight and signal oxidative stress.
Recent Advances: With quantitative immunoelectron microscopy and biochemical
methods, highest ascorbate contents have recently been measured in peroxisomes
(23 mM) and the cytosol (22 mM), lowest ones in vacuoles (2 mM), and intermediate
concentrations (4-16 mM) in all other organelles. CRITICAL ISSUES: The
accumulation of ascorbate in chloroplasts and peroxisomes is crucial for plant
defense. Its depletion in chloroplasts, peroxisomes, and mitochondria during
biotic stress leads to the accumulation of reactive oxygen species (ROS) and the
development of chlorosis and necrosis. In the apoplast and vacuoles, ascorbate is
the most important antioxidant for the detoxification of ROS. The cytosol acts as
a hub for ascorbate metabolism as it reduces its oxidized forms that are produced
in the cytosol or imported from other cell compartments. It is a sink for
ascorbate that is produced in mitochondria, distributes ascorbate to all
organelles, and uses ascorbate to detoxify ROS. As ascorbate and its redox state
are involved in protein synthesis and modifications, it can be concluded that
ascorbate in the cytosol senses oxidative stress and regulates plant growth,
development, and defense. FUTURE DIRECTIONS: Future research should focus on (1)
dissecting roles of ascorbate in vacuoles and the lumen of the endoplasmic
reticulum, (2) identifying the physiological relevance of ascorbate transporters,
and (3) correlating current data with changes in the subcellular distribution of
related enzymes, ROS, and gene expression patterns.
PMID- 28699397
TI - * Glioblastoma Exosomes for Therapeutic Angiogenesis in Peripheral Ischemia.
AB - Peripheral ischemia as a result of occlusive vascular disease is a widespread
problem in patients older than the age of 65. Angiogenic therapies that can
induce microvascular growth have great potential for providing a long-lasting
solution for patients with ischemia and would provide an appealing alternative to
surgical and percutaneous interventions. However, many angiogenic therapies have
seen poor efficacy in clinical trials, suggesting that patients with long-term
peripheral ischemia have considerable therapeutic resistance to angiogenic
stimuli. Glioblastoma is one of the most angiogenic tumor types, inducing robust
vessel growth in the area surrounding the tumor. One major angiogenic mechanism
used by the tumor cells to induce blood vessel growth is the production of
exosomes and other extracellular vesicles that can carry pro-angiogenic and
immunomodulatory signals. Here, we explored whether the pro-angiogenic aspects of
glioblastoma-derived exosomes could be harnessed to promote angiogenesis and
healing in the context of peripheral ischemic disease. We demonstrate that the
exosomes derived from glioblastoma markedly enhance endothelial cell
proliferation and increase endothelial tubule formation in vitro. An analysis of
the microRNA expression using next generation sequencing identified that exosomes
contained a high concentration of miR-221. In addition, we found that
glioblastoma exosomes contained significant amounts of the proteoglycans glypican
1 and syndecan-4, which can serve as co-receptors for angiogenic factors,
including fibroblast growth factor-2 (FGF-2). In a hindlimb ischemia model in
mice, we found that the exosomes promoted enhanced revascularization in
comparison to control alginate gels and FGF-2 treatment alone. Taken together,
our results support the fact that glioblastoma-derived exosomes have powerful
effects in increasing revascularization in the context of peripheral ischemia.
PMID- 28699399
TI - Digital Axillary and Non-Contact Infrared Thermometers for Children.
AB - Axillary digital thermometers (ADTs) and non-contact (infrared) forehead
thermometers (NCIFTs) are commonly used in pediatric settings, where an incorrect
body temperature measurement may delay treatments or lead to incorrect diagnoses
and therapies. Several studies comparing ADT or NCIFT with other methods have
found conflicting results. To investigate whether ADT and NCIFT can be used
interchangeably, a comparative observational study was conducted involving 205
children aged 0 to 14 years who were consecutively admitted to the pediatric
emergency department. The Bland-Altman plot illustrated agreement between the two
methods. A total of 217 pairs of measurements were compared; axillary
measurements showed average values significantly higher than forehead
measurements (37.52 degrees C and 37.12 degrees C; t = 7.42, p = .000), with a
mean difference of 0.41 degrees C between the two methods (range = -1.80 and
+2.40). In this setting and population, ADT and NCIFT cannot be used
interchangeably.
PMID- 28699400
TI - Regulatory Forum Opinion Piece*: Effective Sectioning of Spinal Cord during
Regulatory-type Nonclinical Toxicity Studies.
AB - Regulatory guidelines for nonclinical neurotoxicity testing require spinal cord
evaluation but do not specify a trimming scheme. The Society of Toxicologic
Pathology (STP) "best practices" for nervous system sampling during nonclinical
general toxicity studies recommend that spinal cord be assessed in both
longitudinal/oblique and transverse sections. This article defines possible
longitudinal/oblique orientations, describes their benefits and challenges, and
provides an expert recommendation regarding suitable trimming planes.
Longitudinal parasagittal (LP) sections follow a vertical plane just lateral to
the midline, revealing sensory and motor tracts but little gray matter.
Longitudinal horizontal sections transect only sensory or motor tracts and
variable quantities of gray matter. Oblique vertical (OV) sections angle across
the spinal cord from side to side. Oblique transverse (OT) sections slant through
from top (dorsal [posterior]) to bottom (ventral [anterior]). Compared to
longitudinal planes, oblique orientations demonstrate considerably more gray
matter and white matter. Current STP "best practices" explicitly recommend the LP
and OV options; the OT orientation also will yield suitable sections while
permitting assessment of anatomic symmetry. Selection among the LP, OT, and OV
planes should be at the discretion of the study pathologist. The bilaterally
symmetrical OT sections likely will be analyzed most easily by
nonneuropathologists.
PMID- 28699401
TI - Student Hunger on Campus: Food Insecurity Among College Students and Implications
for Academic Institutions.
AB - PURPOSE: To estimate the prevalence of food insecurity among students at a large
mid-Atlantic publicly funded university; examine the association between food
insecurity, demographic characteristics, potential financial risk factors, and
self-reported physical and mental health and academic performance; and identify
possible risk factors for food insecurity. DESIGN: Cross-sectional survey.
SETTING: Large, public mid-Atlantic university. PARTICIPANTS: Two hundred thirty
seven undergraduate students. MEASURES: US Department of Agriculture (USDA) 18
item Household Food Security Survey Module (HFSSM) and questions on demographics,
student status, economic factors, housing stability, living arrangements,
academic performance, and self-rated physical health and depression symptoms.
ANALYSIS: Multivariate logistic regression analysis. RESULTS: Among students
surveyed, 15% were food insecure; an additional 16% were at risk of food
insecurity. Students who were African American, other race/ethnicity, receiving
multiple forms of financial aid, or experiencing housing problems were more
likely to be food insecure or at the risk of food insecurity (Adjusted Odds Ratio
[AOR] = 4.00, 95% confidence interval [CI] = 1.83-8.71, P value < .0001; AOR =
5.26, 95% CI = 1.85-14.98, P value = .002; AOR = 3.43, 95% CI = 1.85-6.37, P
value <.001; AOR = 8.00, 95% CI = 3.57-17.93, P value < .0001, respectively).
Food secure students were less likely to report depression symptoms than at-risk
or food insecure students. CONCLUSION: Food insecurity among college students is
an important public health concern that might have implications for academic
performance, retention, and graduation rates. Universities that measure food
insecurity among their students will be better positioned to advocate for policy
changes at state and federal levels regarding college affordability and student
financial assistance.
PMID- 28699402
TI - The management of episiotomy technique and its effect on pelvic floor muscles
during a malposition childbirth.
AB - Vaginal childbirth is the leading cause of pelvic floor muscles injury, which
contributes to pelvic floor dysfunction, being enhanced by fetal malposition.
Therefore, the aim of the present study is to verify the influence of
mediolateral episiotomies in the mechanics of the pelvic floor with the fetus in
occiput posterior position when compared to the occiput anterior position.
Numerical simulations of vaginal deliveries, with and without episiotomy, are
performed based on the Finite Element Method. The biomechanical model includes
the pelvic floor muscles, a surface to delimit the anterior region of the birth
canal and a fetus. Fetal malposition induces greater extension of the muscle
compared to the normal position, leading to increases of stretch. The faster
enlargement may be responsible for a prolonged second stage of labor. Regarding
the force required to achieve delivery, the difference between the analyzed cases
are 35 N, which might justify the increased need of surgical interventions.
Furthermore, episiotomy is essential in reducing the damage to values near the
ones obtained with normal position, making the fetal position irrelevant. These
biomechanical models have become extremely useful tools to provide some
understanding of pelvic floor function during delivery helping in the development
of preventative strategies.
PMID- 28699403
TI - RNA-Seq investigations of human post-mortem trigeminal ganglia.
AB - Background The trigeminal ganglion contains neurons that relay sensations of
pain, touch, pressure, and many other somatosensory modalities to the central
nervous system. The ganglion is also a reservoir for latent herpes virus 1
infection. To gain a better understanding of molecular factors contributing to
migraine and headache, transcriptome analyses were performed on postmortem human
trigeminal ganglia. Methods RNA-Seq measurements of gene expression were
conducted on small sub-regions of 16 human trigeminal ganglia. The samples were
also characterized for transcripts derived from viral and microbial genomes.
Herpes simplex virus 1 (HSV-1) antibodies in blood were measured using the
luciferase immunoprecipitation assay. Results Observed molecular heterogeneity
could be explained by sampling of anatomically distinct sub-regions of the
excised ganglia consistent with neurally-enriched and non-neural, i.e. Schwann
cell, enriched subregions. The levels of HSV-1 transcripts detected in trigeminal
ganglia correlated with blood levels of HSV-1 antibodies. Multiple migraine
susceptibility genes were strongly expressed in neurally-enriched trigeminal
samples, while others were expressed in blood vessels. Conclusions These data
provide a comprehensive human trigeminal transcriptome and a framework for
evaluation of inhomogeneous post-mortem tissues through extensive quality control
and refined downstream analyses for RNA-Seq methodologies. Expression profiling
of migraine susceptibility genes identified by genetic association appears to
emphasize the blood vessel component of the trigeminovascular system. Other genes
displayed enriched expression in the trigeminal compared to dorsal root ganglion,
and in-depth transcriptomic analysis of the KCNK18 gene underlying familial
migraine shows selective neural expression within two specific populations of
ganglionic neurons. These data suggest that expression profiling of migraine
associated genes can extend and amplify the underlying neurobiological insights
obtained from genetic association studies.
PMID- 28699404
TI - Improved external rotation with concomitant reverse total shoulder arthroplasty
and latissimus dorsi tendon transfer: A systematic review.
AB - BACKGROUND: In conjunction with reverse total shoulder arthroplasty (RSA),
latissimus dorsi and teres major (LD-TM) transfer has been advocated in the
setting of combined loss of elevation and external rotation. The purpose of this
systematic review is to summarize the clinical outcomes following RSA with LD-TM
transfer. METHODS: A search of PubMed, EMBASE, CINAHL, Medline, and Cochrane
databases was performed between January 1, 1990 and March 1, 2016 and included
articles related to outcomes following RSA with LD-TM transfer. Primary outcomes
of interest were constant score, shoulder range of motion, and patient
satisfaction. Secondary outcomes of interest included subjective shoulder value,
simple shoulder test, activities of daily living requiring external rotation, and
visual analog pain score. Additional outcomes evaluated included complications
and reoperations. Frequency-weighted values of outcome data were utilized.
RESULTS: Five level IV studies involving 98 shoulders met the inclusion criteria.
The mean age of the cohort was 69.1 +/- 5.19 years (range 47-85). RSA with LD-TM
transfer was performed for rotator cuff arthropathy (94%) or proximal humerus
fracture (6%). The average follow-up was 44.5 +/- 10.38 months (range 12-105
months). The constant score improved from 28 to 65 ( p < 0.0005). Active external
rotation improved from -7.4 degrees to 22.9 degrees ( p < 0.0005). There was a
22.4% overall complication rate, including dislocation (5.1%), infection (5.1%),
and transient nerve palsy (3.4%). CONCLUSION: Patients undergoing RSA with LD-TM
transfer in the setting of loss of external rotation demonstrate reliable
clinical improvements in shoulder function with complication rates which are
comparable to RSA alone.
PMID- 28699405
TI - Cut-off values of the Japanese Orthopaedic Association score corresponding to
Constant scores for evaluating outcomes in rotator cuff tear.
AB - PURPOSE: To clarify the cut-off value of the Japanese Orthopaedic Association
(JOA) score corresponding to rotator cuff tear outcome as evaluated by the
Constant score. METHODS: The subjects were 230 patients with rotator cuff tear.
The Constant and JOA scores on the first examination in our hospital were
evaluated. After investigation of the correlation between the Constant and JOA
scores, the cut-off JOA score was calculated, corresponding to excellent, good
and fair outcomes as evaluated by the Constant score. RESULTS: The Constant and
JOA scores on the first examination were 49.64 +/- 12.84 and 72.52 +/- 12.84,
respectively, with a strong correlation ( r = 0.87, p < 0.01). Receiver operating
characteristic analysis revealed that the cut-off JOA score was 87.0 for
excellent outcome (area under the curve, AUC: 0.93; sensitivity: 100%;
specificity: 88.6%; p < 0.01), 84.0 for good outcome (AUC: 0.94; sensitivity:
100%; specificity: 83.4%; p < 0.01) and 78.0 for fair outcome (AUC: 0.88;
sensitivity: 100%; specificity: 71.3%; p < 0.01). CONCLUSIONS: In patients with
rotator cuff tear, good outcome as judged by a Constant score of >=80 corresponds
to a JOA score cut-off of 84.0. Judgement of the treatment outcomes and
evaluation of the surgical method may be more accurate when using clear cut-off
values for the scoring system employed, such as those determined in our study.
PMID- 28699406
TI - Disruption of quadriceps tendon after total knee arthroplasty: Case report of
four cases.
AB - Quadriceps tendon rupture after total knee arthroplasty (TKA) is a rare but dire
complication. It is associated with adverse outcomes and morbidities. Studies on
such complications are scarce in the literature. In this study, we share our
experience in the management of four patients who sustained quadriceps tendon
rupture in the early postoperative period. Efforts should be focused on
prevention. Meticulous surgical techniques during the medial parapatellar
approach to preserve the integrity of quadriceps can reduce the risk of rupture.
The importance of prompt diagnosis is emphasized as delayed treatment may lead to
poor outcomes. However, making a diagnosis can be challenging, as worsening of
the quadriceps strength after TKA is expected because of the surgical approach
that violates the quadriceps muscle. In an event of postoperative trauma with
resultant extensor weakness, an ultrasound evaluation to exclude a quadriceps
tendon rupture should be promptly performed after a fracture is excluded.
PMID- 28699407
TI - Hydrogen Sulfide and Glucose Homeostasis: A Tale of Sweet and the Stink.
AB - SIGNIFICANCE: Among many endogenous mediators, the gasotransmitter hydrogen
sulfide (H2S) plays an important role in the regulation of glucose homeostasis.
In this article we discuss different functional roles of H2S in several metabolic
organs/tissues required in the maintenance of glucose homeostasis. Recent
Advances: New evidence has emerged revealing the insulin sensitizing role of H2S
in adipose tissue and skeletal muscle biology. In addition, H2S was demonstrated
to be a potent stimulator of gluconeogenesis via the induction and stimulation of
various glucose-producing pathways in the liver. CRITICAL ISSUES: Similar to its
other physiological effects, H2S exhibits paradoxical characteristics in the
regulation of glucose homeostasis: (1) H2S stimulates glucose production via
activation of gluconeogenesis and glycogenolysis in hepatocytes, yet inhibits
lipolysis in adipocytes; (2) H2S stimulates glucose uptake into adipocytes and
skeletal muscle but inhibits glucose uptake into hepatocytes; (3) H2S inhibits
insulin secretion from pancreatic beta cells, yet sensitizes insulin signaling
and insulin-triggered response in adipose tissues and skeletal muscle. It is also
unclear the impact H2S may have on glucose metabolism and utilization by other
vital organs, such as the brain. FUTURE DIRECTIONS: Recent reports and ongoing
studies lay the foundation for a general, although highly incomplete,
understanding of the effect of H2S on regulating glucose homeostasis. In this
review, we describe the molecular mechanisms and physiological outcomes of the
gasotransmitter H2S on organs and tissues required for homeostatic maintenance of
blood glucose. Future directions highlighting the H2S-mediated homeostatic
control of glucose metabolism under physiological and insulin-resistant
conditions are also discussed. Antioxid. Redox Signal. 28, 1463-1482.
PMID- 28699408
TI - Bridging the gap between heart failure and the device clinic.
AB - INTRODUCTION: While cardiac resynchronization therapy (CRT) is a mainstay in the
management of selected patients with chronic systolic dysfunction, many patients
are noted to experience less than expected or no benefit at all from the therapy.
Multidisciplinary care has been shown to provide benefit in follow up for
patients receiving CRT devices. Areas covered: This review will focus on the
apparent reasons behind less than optimal outcomes following CRT as well as
multidisciplinary approaches to treating patients with CRT devices. The
literature review focused mainly on the data behind multidisciplinary care of CRT
patients. Expert commentary: A multidisciplinary approach incorporating input
from various cardiology backgrounds is an important strategy in ensuring optimal
outcomes in patients receiving CRT devices. Breaking down the 'silo' effect
amongst cardiac subspecialties is vital in achieving high level multidisciplinary
care.
PMID- 28699409
TI - Review of the Effectiveness of Enteral Feeding in Pediatric Oncology Patients
[Formula: see text].
AB - Enteral supplementation for nutritional support in pediatric oncology patients
remains nonstandardized across institutions and between providers. Pediatric
oncology patients frequently fail to meet their growth curve percentiles, lose
weight, and/or are malnourished due to both the oncologic process as well as side
effects from chemotherapy and radiation treatments. Methods of increasing weight
include enteral feeding (nasogastric, nasoduodenal/jejunal, or gastrostomy),
parenteral intravenous feeding, and oral supplementation. Indications for feeding
and feeding protocols are highly variable, in part due to parental and familial
choices, and in part due to the lack of guidelines available for providers. This
article provides a comprehensive literature review of 8 published studies
regarding the effectiveness and safety of enteral feeding in maintaining or
increasing weight in pediatric oncology patients to help inform practice. The
review concludes that enteral feeding in pediatric oncology patients is an
effective and safe method to affect weight positively. However, further research
is needed for developing treatment guidelines, including establishing a timeline
for initiation of feeding, and determining which patients are most likely to
benefit from enteral feeding.
PMID- 28699410
TI - A patient's perspective of chronic pain.
AB - Sara Gilbert Nadler speaks to Jade Parker, Commissioning Editor: Sara has
obtained a Bachelor's Degree and Master's in social work. Her field of practice
in social work has been in the field of medical social work. Sara has worked in
the field of medical social work for over 20 years; her work has spanned from
acute care hospitals to skilled nursing facilities. Her professional
responsibilities include case management, discharge planning, financial
management, counselling patients and their families in regard to their medical
conditions as well as making referrals to home care agencies and other care
providers if necessary. At present she is a volunteer at Community Health
Advocates, New York. She works on the telephone help line, handles health
insurance issues along with answering questions in regard to the affordable care
act. She also advocates if a client is having issues with their health insurance
company in terms of coverage issues. She works with the client and their
insurance company and any other agency that needs to advocate on their behalf.
PMID- 28699411
TI - Ethnic disparities in educational and occupational gradients of estimated
cardiovascular disease risk: The Healthy Life in an Urban Setting study.
AB - BACKGROUND: European societies are becoming increasingly ethnically diverse. This
may have important implications for socio-economic inequalities in health due to
the often disadvantaged position of ethnic minority groups in both socio-economic
status (SES) and disease, especially cardiovascular disease (CVD). OBJECTIVE: The
aim of this study was to determine whether the socio-economic gradient of
estimated CVD risk differs between ethnic groups. METHODS: Using the Healthy Life
in an Urban Setting study, we obtained data on SES and CVD risk factors among
participants from six ethnic backgrounds residing in Amsterdam. SES was measured
using educational level and occupational level. CVD risk was estimated based on
the occurrence of CVD risk factors using the Dutch version of the systematic
coronary risk evaluation algorithm. Ethnic disparities in socio-economic
gradients for estimated CVD risk were determined using the relative index of
inequality (RII). RESULTS: Among Dutch-origin men, the RII for estimated CVD risk
according to educational level was 6.15% (95% confidence interval [CI] 4.35
7.96%), indicating that those at the bottom of the educational hierarchy had a
6.15% higher estimated CVD risk relative than those at the top. Among Dutch
origin women, the RII was 4.49% (CI 2.45-6.52%). The RII was lower among ethnic
minority groups, ranging from 0.83% to 3.13% among men and -0.29% to 5.12% among
women, indicating weaker associations among these groups. Results were similar
based on occupational level. CONCLUSIONS: Ethnic background needs to be
considered in associations between SES and disease. The predictive value of SES
varies between ethnic groups and may be quite poor for some groups.
PMID- 28699412
TI - Pressure Autoregulation Measurement Techniques in Adult Traumatic Brain Injury,
Part II: A Scoping Review of Continuous Methods.
AB - A scoping review of the literature was performed systematically on commonly
described continuous autoregulation measurement techniques in adult traumatic
brain injury (TBI) to provide an overview of methodology and comprehensive
reference library of the available literature for each technique. Five separate
small systematic reviews were conducted for each of the continuous techniques:
pressure reactivity index (PRx), laser Doppler flowmetry (LDF), near infrared
spectroscopy (NIRS) techniques, brain tissue oxygen tension (PbtO2), and thermal
diffusion (TD) techniques. Articles from MEDLINE, BIOSIS, EMBASE, Global Health,
Scopus, Cochrane Library (inception to December 2016), and reference lists of
relevant articles were searched. A two-tier filter of references was conducted.
The literature base identified from the individual searches was limited, except
for PRx. The total number of articles using each of the five searched techniques
for continuous autoregulation in adult TBI were: PRx (28), LDF (4), NIRS (9),
PbtO2 (10), and TD (8). All continuous techniques described in adult TBI are
based on moving correlation coefficients. The premise behind the calculation of
these moving correlation coefficients focuses on the impact of slow fluctuations
in either mean arterial pressure (MAP) or cerebral perfusion pressure (CPP) on
some indirect measure of cerebral blood flow (CBF), such as: intracranial
pressure (ICP), LDF, NIRS signals, PbtO2, or TD CBF. The thought is the
correlation between a hemodynamic driving factor, such as MAP or CPP, and a
surrogate for CBF or cerebral perfusion sheds insight on the state of cerebral
autoregulation. Both PRx and NIRS indices were validated experimentally against
the "gold standard" static autoregulatory curve (Lassen curve) at least around
the lower threshold of autoregulation. The PRx has the largest literature base
supporting the association with patient outcome. Various methods of continuous
autoregulation assessment are described within the adult TBI literature. Many
studies exist on these various indices, suggesting an association between their
values and patient morbidity/death.
PMID- 28699413
TI - Getting Both Practical and Academic Value Out of a Study.
PMID- 28699414
TI - Role of Ultrasound in Predicting Tumor Invasiveness in Follicular Variant of
Papillary Thyroid Carcinoma.
AB - BACKGROUND: Follicular variant of papillary thyroid carcinoma (FVPTC) is
traditionally divided into infiltrative and encapsulated types. Adding to this
classification, noninvasive follicular thyroid neoplasm with papillary-like
nuclear features (NIFTP) represents a reclassification of a subset of cases
(encapsulated tumors without lymphovascular or capsular invasion). The purpose of
this study was to assess the role of ultrasound (US) in predicting tumor
invasiveness in FVPTC. METHODS: From January 2014 to May 2016, preoperative US
examinations were performed on 151 patients with 152 FVPTCs who underwent
surgery. Based on a pathologic analysis, the FVPTCs were categorized into three
groups: NIFTP, invasive encapsulated FVPTC (iE-FVPTC), or infiltrative FVPTC (I
FVPTC). Each nodule was categorized based on the US pattern according to the
Korean Thyroid Imaging Reporting and Data System (K-TIRADS) and the American
Thyroid Association (ATA) guidelines. The correlation between tumor invasiveness
and the K-TIRADS or ATA category was investigated using Spearman's rank
correlation coefficient. RESULTS: Among the 152 FVPTCs, there were 48 (31.6%)
NIFTPs, 60 (39.5%) iE-FVPTCs, and 44 (28.9%) I-FVPTCs. US characteristics of the
FVPTCs differed significantly according to tumor invasiveness (p <= 0.030). Tumor
invasiveness showed a significant positive correlation with K-TIRADS (tumors of
all sizes: r = 0.591, p < 0.001; tumors >=1.0 cm: r = 0.427, p < 0.001) and ATA
categories (tumors of all sizes: r = 0.532, p < 0.001; tumors >=1.0 cm: r =
0.466, p < 0.001). According to both K-TIRADS and ATA guidelines for all-sized
tumors, the most common subtype was NIFTP in low-suspicion nodules (52.6% and
51.6%), iE-FVPTC in intermediate-suspicion nodules (52.7% and 54.2%), and I-FVPTC
in high-suspicion nodules (82.5% and 69.4%). After surgery, lymph node metastases
were confirmed in two (4.2%) NIFTP cases, three (5.0%) iE-FVPTC cases, and eight
(18.2%) I-FVPTC cases (p = 0.001). The results of the BRAF mutation analysis were
not significantly different between the groups (p = 0.507). CONCLUSIONS:
Increasing tumor invasiveness from NIFTP to iE-FVPTC to I-FVPTC is positively
correlated with the level of suspicion on US using both K-TIRADS and ATA
guidelines.
PMID- 28699415
TI - A Scalable Approach for the Generation of Human Pluripotent Stem Cell-Derived
Hepatic Organoids with Sensitive Hepatotoxicity Features.
AB - The quest for physiologically active human hepatocyte-like cells for in vitro
research and drug screening is high. The recent progress in the field of
pluripotent stem cell (PSC)-derived hepatic cells within the last decade brings
those cells closer to applications in translational medicine. However, the
classical two-dimensional (2D) cell culture systems are of limited use, because
relevant cell-cell interactions based on cell polarity, which is a major
prerequisite for proper hepatic cell metabolisms, are not provided. In this
study, we report a scalable 3D suspension culture system, in which PSC-derived
hepatic cells can be maintained for up to 3 weeks with stable gene expression
profiles and metabolic features in a suspension culture system ranging from a 1.5
mL up to a 15 mL. Adjustments of culture conditions and, most importantly, the
size of the organoids resulted in the robust generation of hepatic organoids
consisting of a quite homogenous cell population. Importantly, the generation of
these hepatic organoids was highly reproducible and allowed, in contrast to
hepatic PSC derivatives in 2D culture conditions, a sensitive assessment of
acetaminophen-related toxicity, the most common source for drug-induced liver
failure.
PMID- 28699416
TI - Interview with David Tauben: University of Washington, Chief of the Division of
Pain Medicine.
AB - Dr Tauben is Clinical Professor jointly appointed in the Departments of Medicine
and Anesthesia & Pain Medicine, and is the Hughes M & Katherine G Blake Endowed
Professor, board certified in both Internal Medicine and Pain Medicine. He is
also University of Washington (UW) Director of Medical Student and Resident
Education in Pain Medicine, and Medical Director of UW TelePain, a tele-video
conferencing program intended to provide innovative pain education and
consultative support to a five-state northwest regional primary care providers.
He served as a member of the NIH National Pain Strategy task force on pain
education and is principal investigator for the UW's prestigious NIH Pain
Consortium Center of Excellence for Pain Education, leading curriculum
development to extend the pain proficiency qualifications of interprofessional
primary care providers. Dr Tauben is a member of the American Pain Society and
the International Association for the Study of Pain special interest study groups
on Pain Education. He is a founding member of the State of Washington Agency
Medical Directors panel of medical experts developing opioid prescription
guidelines for the state, and a regular clinical and content expert for
regulatory and legislative bodies involved in public policy regarding pain
medicine practice and standards. He speaks as a clinical expert in medical
management of chronic pain, especially as it applies to primary care practices.
Dr Tauben served as an expert for several US Centers for Disease Control clinical
outreach programs and policy reviews advising primary care providers on how to
prescribe opioids for chronic noncancer pain. He is annually recognized by his
peers as recipient of regional awards in care of pain patients, and brings
decades of clinical experience of best practice medication management of acute
and chronic pain. Dr Tauben received his bachelors degree in philosophy from Yale
University, medical degree from Tufts University School of Medicine and completed
his residency training at the UW, in Seattle. He is a fellow of the American
College of Physicians.
PMID- 28699417
TI - Comparison of metal ion concentrations and implant survival after total hip
arthroplasty with metal-on-metal versus metal-on-polyethylene articulations.
AB - Background and purpose - Large metal-on-metal (MoM) articulations are associated
with metal wear and corrosion, leading to increased metal ion concentrations and
unacceptable revision rates. There are few comparative studies of 28-mm MoM
articulations with conventional metal-on-polyethylene (MoP) couplings. We present
a long-term follow-up of a randomized controlled trial comparing MoM versus MoP
28-mm articulations, focused on metal ions and implant survival. Patients and
methods - 85 patients with a mean age of 65 years at surgery were randomized to a
MoM (Metasul) or a MoP (Protasul) bearing. After 16 years, 38 patients had died
and 4 had undergone revision surgery. 13 patients were unavailable for clinical
follow-up, leaving 30 patients (n = 14 MoM and n = 16 MoP) for analysis of metal
ion concentrations and clinical outcome. Results - 15-year implant survival was
similar in both groups (MoM 96% [95% CI 88-100] versus MoP 97% [95% CI 91-100]).
The mean serum cobalt concentration was 4-fold higher in the MoM (1.5 MUg/L)
compared with the MoP cohort (0.4 MUg/L, p < 0.001) and the mean chromium
concentration was double in the MoM (2.2 MUg/L) compared with the MoP cohort (1.0
MUg/L, p = 0.05). Mean creatinine levels were similar in both groups (MoM 93
MUmol/L versus MoP 92 MUmol/L). Harris hip scores differed only marginally
between the MoM and MoP cohorts. Interpretation - This is the longest follow-up
of a randomized trial on 28-mm MoM articulations, and although implant survival
in the 2 groups was similar, metal ion concentrations remained elevated in the
MoM cohort even in the long term.
PMID- 28699418
TI - Evaluation of Deformable Image Registration-Based Contour Propagation From
Planning CT to Cone-Beam CT.
AB - PURPOSE: We evaluated the performance of organ contour propagation from a
planning computed tomography to cone-beam computed tomography with deformable
image registration by comparing contours to manual contouring. MATERIALS AND
METHODS: Sixteen patients were retrospectively identified based on showing
considerable physical change throughout the course of treatment. Multiple organs
in the 3 regions (head and neck, prostate, and pancreas) were evaluated. A cone
beam computed tomography from the end of treatment was registered to the planning
computed tomography using rigid registration, followed by deformable image
registration. The contours were copied on cone-beam computed tomography image
sets using rigid registration and modified by 2 radiation oncologists. Contours
were compared using Dice similarity coefficient, mean surface distance, and
Hausdorff distance. RESULTS: The mean physician-to-physician Dice similarity
coefficient for all organs was 0.90. When compared to each physician's contours,
the overall mean for rigid was 0.76 ( P < .001), and it was improved to 0.79 ( P
< .001) for deformable image registration. Comparing deformable image
registration to physicians resulted in a mean Dice similarity coefficient of
0.77, 0.74, and 0.84 for head and neck, prostate, and pancreas groups,
respectively; whereas, the physician-to-physician mean agreement for these sites
was 0.87, 0.90, and 0.93 ( P < .001, for all sites). The mean surface distance
for physician-to-physician contours was 1.01 mm, compared to 2.58 mm for rigid-to
physician contours and 2.24 mm for deformable image registration-to-physician
contours. The mean physician-to-physician Hausdorff distance was 11.32 mm, and
when compared to any physician's contours, the mean for rigid and deformable
image registration was 12.1 mm and 12.0 mm ( P < .001), respectively. CONCLUSION:
The physicians had a high level of agreement via the 3 metrics; however,
deformable image registration fell short of this level of agreement. The
automatic workflows using deformable image registration to deform contours to
cone-beam computed tomography to evaluate the changes during treatment should be
used with caution.
PMID- 28699419
TI - Chair rise capacity and associated factors in older home-care clients.
AB - AIMS: The aim of this study was to investigate the ability of older home-care
clients to perform the five times chair rise test and associated personal
characteristics, nutritional status and functioning. METHODS: The study sample
included 267 home-care clients aged >=75 years living in Eastern and Central
Finland. The home-care clients were interviewed at home by home-care nurses,
nutritionists and pharmacists. The collected data contained sociodemographic
factors, functional ability (Barthel Index, IADL), cognitive functioning (MMSE),
nutritional status (MNA), depressive symptoms (GDS-15), medical diagnoses and
drug use. The primary outcome was the ability to perform the five times chair
rise test. RESULTS: Fifty-one per cent ( n=135) of the home-care clients were
unable to complete the five times chair rise test. Twenty-three per cent ( n=64)
of the home-care clients had good chair rise capacity (<=17 seconds). In a
multivariate logistic regression analysis, fewer years of education (odds ratio
[OR] = 1.11, 95% confidence interval [CI] 1.04-1.18), lower ADL (OR = 1.54, 95%
CI 1.34-1.78) and low MNA scores (OR = 1.12, 95% CI 1.04-1.20) and a higher
number of co-morbidities (OR = 1.21, 95% CI 1.02-1.43) were associated with
inability to complete the five times chair rise test. CONCLUSIONS: Poor
functional mobility, which was associated with less education, a high number of
co-morbidities and poor nutritional status, was common among older home-care
clients. To maintain and to prevent further decline in functional mobility,
physical training and nutritional services are needed. (NutOrMed,
ClinicalTrials.gov Identifier: NCT02214758).
PMID- 28699420
TI - Referral Trends for Surgical Management of Graves' Disease.
PMID- 28699421
TI - Global cancer pain management: a systematic review comparing trials in Africa,
Europe and North America.
AB - AIM: Despite the rise in cancer survivorship, few reviews have examined the
quality of studies of cancer pain management and practices around the globe. With
a void in trials spanning multiple geographical settings, this review evaluates
the quality of cancer trials across three continents. MATERIALS & METHODS: A
literature review and search of established databases was conducted to identify
eligible studies. The Cochrane method, the Jadad Score and a cancer pain-specific
ad hoc tool were used to evaluate quality of studies. RESULTS: Eighteen studies
representing a total of 4693 individuals were included in the review. Study
quality correlated positively with study sample size and palliative care index.
Trials in all three continents were prone to use opioids for pain management,
whereas trials in Europe and North America utilized other adjuvant therapies such
as antidepressants and steroids. CONCLUSION: This review underscores the need for
better multidimensional quality assessment tools for cancer pain trials.
PMID- 28699422
TI - Corrigendum.
PMID- 28699423
TI - Reversal of Smoking Effects on Chronic Rhinosinusitis after Smoking Cessation.
AB - Objective To understand whether the impact of smoking on chronic rhinosinusitis
(CRS) is reversible after smoking cessation. Study Design Cross-sectional study.
Setting Academic tertiary care rhinology clinic. Subjects and Methods A total of
103 former-smoker CRS patients and 103 nonsmoker CRS patients were prospectively
recruited. The primary outcome measure was sinonasal symptom severity measured
with the 22-item Sinonasal Outcomes Test (SNOT-22), and secondary outcome
measures were general health-related quality of life (QOL) measured with the 5
dimensional EuroQol visual analog scale (EQ-5D VAS) and patient-reported CRS
related antibiotic and oral corticosteroid usage in the past year. Outcome
measures were compared between cohorts and checked for association with time
since cessation of smoking for former smokers. Results Compared with nonsmokers,
former smokers had worse SNOT-22 score ( P = .019) and EQ-5D VAS score ( P =
.001) and reported using more CRS-related antibiotics ( P = .003) and oral
corticosteroids in the past year ( P = .013). In former smokers, every year was
associated with a statistically significant improvement in SNOT-22 score (beta =
0.48; 95% CI, -0.91 to -0.05; P = .032), EQ-5D VAS score (beta = 0.46; 95% CI,
0.02-0.91; P = .046), and CRS-related oral corticosteroid use (relative risk =
0.95; 95% CI, 0.91-0.98; P = .001). Given the differences in our study outcome
measures between former smokers and nonsmokers, we estimate that the reversible
impacts of smoking on CRS may resolve after 10 to 20 years. Conclusions CRS
patients who are former smokers have worse sinonasal symptomatology, QOL, and CRS
related medication usage than nonsmokers. Every year since cessation of smoking
is associated improvements in sinonasal symptomatology, QOL, and CRS-related oral
corticosteroid use, potentially reaching nonsmoker levels after 10 to 20 years.
PMID- 28699424
TI - Endovascular repair of subclavian artery aneurysms: results from a single-center
experience.
AB - OBJECTIVE: To present our experience of the endovascular treatment of subclavian
artery aneurysms (SAAs) and analyze the clinical manifestations, imaging findings
and treatment outcomes. METHODS: In this retrospective study, nine patients with
SAAs underwent endovascular stent placement in our center between July 2011 and
June 2016. Clinical features, imaging findings, treatment outcomes and follow-up
results of these SAA patients were retrospectively analyzed. RESULTS: Nine
patients were diagnosed with SAAs by computer tomography angiography (CTA). Five
patients underwent percutaneous endovascular stent placement in the subclavian
artery. Three patients underwent endovascular repair of the SAAs with coil
embolization and stent graft. One patient underwent stent graft implantation by
the simultaneous kissing stent technique. Five patients had their symptoms
relieved and thrombosis occurred in one case. The mean follow-up period was 17
months, ranging from 8 to 40 months. CONCLUSION: For patients with SAAs,
endovascular treatment is a feasible choice, with a high success rate, few
complications and good clinical outcomes.
PMID- 28699425
TI - Do health complaints in adolescence negatively predict the chance of entering
tertiary education in young adulthood?
AB - BACKGROUND: Self-reported psychological and psychosomatic health complaints, such
as nervousness, sadness, headache and stomach-ache, are common among adolescents,
particularly among girls, and studies suggest that the prevalence has risen among
adolescent girls during the last few decades. However, only a limited number of
studies have investigated the potential long-term consequences of such health
complaints. The aim of the current study was to assess whether psychological and
psychosomatic health complaints in adolescence predict the chance of entering
tertiary education in young adulthood among women and men. METHODS: The data used
are from the Swedish Young-LNU, which is based on a nationally representative
sample with self-reported survey information from adolescents aged 10-18 years in
2000 and from the same individuals at ages 20-28 in 2010 ( n=783). Information
was also collected from parents and from official registers. RESULTS: Linear
probability models showed that self-reported psychological complaints in
adolescence were associated with a lower chance of having entered tertiary
education 10 years later. This association was accounted for by differences in
grade point average (GPA), suggesting that GPA may mediate the association
between psychological complaints and later education. The pattern was similar for
both genders. Furthermore, among men, psychosomatic complaints in adolescence
were significantly associated with a lower likelihood of having entered tertiary
education 10 years later when adjusting for GPA and social class in adolescence.
A similar but non-significant tendency was found among women. CONCLUSIONS: The
findings suggest that health complaints in adolescence may have long-term
consequences in terms of lower educational attainment.
PMID- 28699426
TI - Management of hemothorax after thoracic endovascular aortic repair for ruptured
aneurysms.
AB - Background Thoracic aortic aneurysm rupture is often a fatal condition. Emergent
thoracic endovascular aortic repair (TEVAR) has emerged as a suitable treatment
option. Unfortunately, respiratory complications from hemothorax continue to be
an important cause of morbidity and mortality even after successful management of
the aortic rupture. We hypothesize that early hemothorax decompression after
TEVAR for ruptured aneurysms decreases the rate of postoperative respiratory
complications. Methods Single-center, retrospective eight-year review of ruptured
thoracic aneurysms treated with TEVAR. Results Seventeen patients presented with
ruptured degenerative thoracic aortic aneurysms, all of which were successfully
treated emergently with TEVAR. The mean age was 74 years among the 12 (70.6%) men
and 5 (29.4%) women treated. Inpatient and 30-day mortality rates for the entire
cohort were both 17.6% (three patients). The 90-day mortality rate was 47.1%
(eight patients). Thirty-day morbidities of the entire cohort included stroke ( n
= 1, 5.9%), spinal cord ischemia ( n = 3, 17.6%; only one was temporary), cardiac
arrest ( n = 4, 23.5%; 3 were fatal), respiratory failure ( n = 5, 29.4%), and
renal failure ( n = 5, 29.4%). A large hemothorax was identified in the majority
of patients ( n = 14, 82.4%). While six (42.9% of 14) patients had immediate
chest tube decompression on the day of index procedure, three (21.4% of 14)
patients had decompression on postoperative day 1, 4, and 7, respectively.
Although not statistically significant, there were trends toward higher rates of
respiratory failure (50.0% vs. 16.7%, P = 0.198) and 90-day mortality (62.5% vs.
33.3%, P = 0.280) for patients with delayed or no hemothorax decompression when
compared to patients with immediate hemothorax decompression. Conclusions The
morbidity and mortality of ruptured degenerative thoracic aortic aneurysms
remains high despite the introduction of TEVAR. In this single-center experience,
there was a trend toward decreased respiratory complications and increased
survival with early chest decompression of hemothorax after TEVAR.
PMID- 28699427
TI - Treatment of Swedish Patients with Graves' Hyperthyroidism Is Associated with
Changes in Acylcarnitine Levels.
AB - BACKGROUND: Hyperthyroidism is associated with alterations in metabolism that are
currently only partially understood. The objective of the study was to
investigate changes in metabolism associated with reinstatement of euthyroidism
in Swedish patients. METHODS: Eighty metabolites in plasma were profiled from 10
subjects with Graves' disease (GD) at baseline and after 9 and 15 months of
treatment to reinstate euthyroidism. Thyroid parameters, thyrotropin (TSH), TSH
receptor antibodies, free triiodothyronine, and free thyroxine were followed.
Main findings were validated in plasma from 20 subjects with GD at baseline and
at three, six, and nine months. The study was conducted at the endocrinology
clinic in Malmo, Sweden. RESULTS: Euthyroidism was reinstated at three months,
and thyroid status did not change further during the 15-month follow-up. This was
paralleled by altered levels of 9/19 detected acylcarnitines (p < 0.05 after
adjustment for multiple testing). Levels of short-chain acylcarnitines were
decreased, intermediate-chain acylcarnitines elevated, and long-chain
acylcarnitines unaltered. CONCLUSIONS: GD and treatment of the disease is
associated with pronounced acyl chain length-dependent alterations in
acylcarnitine levels. These changes may be impacted by ethnicity and or dietary
differences.
PMID- 28699428
TI - Thyrotropin Suppressive Therapy for Low-Risk Small Thyroid Cancer: A Propensity
Score-Matched Cohort Study.
AB - BACKGROUND: Thyrotropin (TSH) suppression has improved the clinical outcomes of
patients with differentiated thyroid cancer (DTC). However, the efficacy of TSH
suppressive therapy (TST) is unclear in patients with low-risk DTC. This study
aimed to evaluate the efficacy of TST and optimal TSH levels of patients with low
risk DTC. METHODS: This retrospective propensity score-matched cohort study
included DTC patients (n = 446) who underwent lobectomy from 2002 to 2008 with or
without TST (TST group and No-TST group). Disease-free survival (DFS) and dynamic
risk stratification were compared between both groups using serum TSH levels.
RESULTS: Approximately 74% of TST patients and 11% of No-TST patients had
suppressed serum TSH levels (<2 mIU/L). The median follow-up period was 8.6
years. During follow-up, the disease recurred in 10 (2.7%) patients, with no
significant difference in DFS between the groups (p = 0.63). The proportion of
patients with excellent treatment response was similar between the TST (65.2%)
and No-TST (64.4%) groups. Incomplete biochemical response was noted in 17.2% of
the TST group patients and 9.4% of the No-TST group patients. No significant
difference was observed in the DFS between both groups by comparing serum TSH
level (p = 0.57). CONCLUSIONS: TST did not improve clinical outcomes, and serum
TSH levels were not associated with recurrence in patients with low-risk small
DTC. No clinical benefits were shown for TSH suppression in low-risk patients who
underwent lobectomy. Thus, levothyroxine is not necessary for patients without
evidence of hypothyroidism.
PMID- 28699429
TI - The order of administration of macrolides and beta-lactams may impact the
outcomes of hospitalized patients with community-acquired pneumonia: results from
the community-acquired pneumonia organization.
AB - BACKGROUND: The beneficial effect of macrolides for the treatment of community
acquired pneumonia (CAP) in combination with beta-lactams may be due to their
anti-inflammatory activity. In patients with pneumococcal meningitis, the use of
steroids improves outcomes only if they are administered before beta-lactams. The
objective of this study was to compare outcomes in hospitalized patients with CAP
when macrolides were administered before, simultaneously with, or after beta
lactams. METHODS: Secondary data analysis of the Community-Acquired Pneumonia
Organization (CAPO) International Cohort Study database. Study groups were
defined based on the sequence of administration of macrolides and beta-lactams.
The study outcomes were time to clinical stability (TCS), length of stay (LOS)
and in-hospital mortality. Accelerated failure time models were used to evaluate
the adjusted impact of sequential antibiotic administration and time-to-event
outcomes, while a logistic regression model was used to evaluate their adjusted
impact on mortality. RESULTS: A total of 99 patients were included in the
macrolide before group and 305 in the macrolide after group. Administration of a
macrolide before a beta-lactam compared to after a beta-lactam reduced TCS (3 vs.
4 days, p = .011), LOS (6 vs. 7 days, p = .002) and mortality (3 vs. 7.2%, p =
.228). CONCLUSIONS: The administration of macrolides before beta-lactams was
associated with a statistically significant decrease in TCS and LOS and a non
statistically significant decrease in mortality. The beneficial effect of
macrolides in hospitalized patient with CAP may occur only if administered before
beta-lactams.
PMID- 28699430
TI - The hot flush: symptom of menopause or sign of disease?
PMID- 28699431
TI - Falls risk assessment.
AB - What was the nature of the CPD activity, practice-related feedback and/or event
and/or experience in your practice? The article discussed falls risk assessment
for older inpatients. It outlined the physical and psychological factors that
nurses should consider when undertaking these assessments, and detailed the
effects that older people may experience as a result of a fall.
PMID- 28699433
TI - Gene discovery will help identify testicular cancer risk.
AB - Researchers have discovered a new group of genes they believe can help identify
men most at risk of testicular cancer.
PMID- 28699432
TI - More time outside can lift mood in older people.
AB - Interventions that increase access to outdoor spaces could positively affect
depressive symptoms in older people, research suggests.
PMID- 28699434
TI - Physical activity for pregnant women.
AB - Essential facts The UK's chief medical officers (CMOs) have published new advice
on physical exercise for pregnant women in the form of an infographic. It is
aimed at providing midwives, nurses, GPs, obstetricians and gynaecologists, as
well as leisure sector professionals, with the latest evidence on physical
activity during pregnancy.
PMID- 28699435
TI - Nurses on film: a century of archives now online.
AB - The growth of online archives has unlocked films showing how previous generations
of nurses were depicted on screen. There aren't that many early examples of real
life nurses on film, but original footage can now be viewed free at the click of
a mouse.
PMID- 28699436
TI - 'The patient is the expert'.
AB - Gary Mitchell trained at Queen's University Belfast, qualifying as a registered
adult nurse in February 2010, aged 24. After working in theatres and recovery, in
a GP practice and as a dementia care adviser, he took up his current post as
national research coordinator and nurse specialist with Four Seasons Health Care
last spring. He is married to Claire and they have a young son called Zach.
PMID- 28699437
TI - Protests won't stop until the cap is scrapped, warns RCN.
AB - The RCN pledged its summer of protest 'has only just started', after the
government insisted the 1% cap on nurse pay will remain.
PMID- 28699438
TI - An evidence-based approach to workforce race equality.
AB - Sheffield Teaching Hospitals NHS Foundation Trust chief executive Sir Andrew Cash
invited me last summer to help develop a system-wide approach to race equality in
the organisation.
PMID- 28699439
TI - Is NMC education reform the beginning of the end for nursing branches?
AB - The Nursing and Midwifery Council has begun its consultation on an education
overhaul it describes as 'radical'. Its new standards are designed to ensure all
nursing students complete their courses with a solid understanding of physical
and mental health care. Some nurses are alarmed by what they see as a move
towards a more generic nurse education system; others are disappointed the
standards do not go far enough in that direction.
PMID- 28699440
TI - 'Nurse cared for me as a patient and inspired me as a colleague'.
AB - I have worked at the same trust as Winnie Nugent and have also been her patient.
For many years she has helped me as a patient at the young onset urology service
at Guy's Hospital in London. She has regularly gone above and beyond what I could
ever have expected of her.
PMID- 28699444
TI - Improvements in safety needed in almost a quarter of care homes.
AB - One in four social care services is failing on safety, according to England's
health and social care regulator.
PMID- 28699441
TI - Maintaining standards in difficult times.
AB - 'We're in a good place in nursing - we've got high-calibre students emerging, and
there's a huge opportunity for nurses to lead change', says Northern Ireland's
chief nurse Charlotte McArdle.
PMID- 28699446
TI - Slow decline in new FGM cases shows need for more school nurses, says RCN.
AB - The RCN has responded to the latest national figures on female genital mutilation
(FGM), saying more school nurses are needed to tackle the problem.
PMID- 28699447
TI - NHS-agency pay gap galling.
AB - I work in a specialist area and have been a band 5 nurse since qualifying in
2000. I'm on the highest pay level for band 5 but get no recognition for any of
the additional skills I have.
PMID- 28699449
TI - Cautious about consent.
AB - Any interaction with a patient requires the patient's consent. Where the patient
cannot give consent, it must be sought from their appointed representative. If
neither of these is possible, the interaction must be in the patient's best
interests.
PMID- 28699450
TI - Pay body not free to do its job.
AB - Tory ministers should come clean on how they enforce the public sector pay cap of
1%.
PMID- 28699451
TI - Competing employers pool resources to attract talent.
AB - A recruitment campaign is linking four healthcare providers with a local
university to promote the benefits of working in their county.
PMID- 28699452
TI - Use social media to motivate patients.
AB - There are challenges and risks in using social media that are well documented in
guidance from the Nursing and Midwifery Council, the RCN and online platforms
such as WeCommunities. Confidentiality, boundaries, appropriate use by vulnerable
groups, and responsible and sensitive communication are recurrent themes. The
unintended consequence of this may be to deter some nurses from using social
media in their professional lives.
PMID- 28699453
TI - Hardship.
AB - A nurse who rushed to treat people during the Grenfell Tower fire has spoken of
her struggle to pay bills.
PMID- 28699455
TI - NMC prepares standards for new associate role.
AB - Professional standards for the work of nursing associates will be drawn up by the
Nursing and Midwifery Council this summer.
PMID- 28699456
TI - Pay rise should be at least 10.
AB - I think a minimum 10% pay rise would retain homegrown nurses. Morale and nursing
levels need to be improved to help reduce stress. When you go to the wire with
nothing to spare in the establishment, and it all goes pear-shaped, everyone
becomes stretched and stressed. Managers should listen to staff at the coal face
about this.
PMID- 28699457
TI - Signalling a deeper understanding.
AB - On placement on a neurological rehabilitation ward, I helped care for a patient
receiving rehabilitation following a stroke.
PMID- 28699458
TI - Suspended sentence for 11-year student bursary fraud that cost the NHS L88,000.
AB - A woman who defrauded the NHS of L88,000 by faking her identity to gain three
nursing student places has been given a suspended prison sentence.
PMID- 28699459
TI - Extended hours hub is a help.
AB - I was interested to read that doctors had called for GP practices to introduce a
'black alert' system that could divert patients from overstretched surgeries
(news, 5 July).
PMID- 28699460
TI - Student life - 'Mum was dying but no one cared - except the student'.
AB - When mum had a fall and was taken to hospital, nobody was looking for anything
life-threatening. But in a matter of days, things went desperately wrong and she
died from an abdominal tumour that had gone undetected.
PMID- 28699461
TI - New blood test could extend prostate cancer survival.
AB - A three-in-one blood test could transform treatment of advanced prostate cancer
through precision drugs targeting mutations in the BRCA genes.
PMID- 28699462
TI - Readers' panel - Is the government's weakened position good or bad for nurses?
AB - Our experts consider a hot topic of the day.
PMID- 28699463
TI - Investigating the attitudes of nurses who are obese.
AB - The prevalence of obesity is higher among nurses than in any other group of
healthcare professionals. Obesity is an issue for the nursing workforce because
of its effects on work-related sickness absence and productivity, through related
conditions such as arthritis and diabetes. Aim To investigate the attitudes,
motivations and behaviours of, and the uptake of workplace health initiatives by,
nurses who are obese. Method Nurses who are or were obese and who practised in
England were recruited at the Royal College of Nursing congress in Glasgow in
June 2016. Participants were asked to complete a short survey on their attitudes
to weight, and the effectiveness and availability of workplace health
initiatives. Results A total of 196 nurses were surveyed, of which 95% (n=186)
wanted to lose weight and 94% (n=185) thought that it was an issue for nurses to
be obese, particularly because being obese made it challenging to discuss weight
loss and healthy lifestyles with patients. Participants expressed an interest in
undertaking workplace health initiatives if these could be accommodated around
their working hours and were free. However, 38% (n=75) of participants reported
that their workplace did not offer any such initiatives to improve staff health.
Conclusion Obesity is often considered to be the result of an individual's
lifestyle choices; however, nurses may experience environmental constraints in
relation to their working practices that may affect their ability to lead healthy
lifestyles. These factors should be addressed to reduce the high levels of
obesity in the nursing workforce.
PMID- 28699464
TI - Unrelenting time and ever-crazy workloads.
AB - The sight of Big Ben and the sound of its iconic chime hold no romance for me.
Instead, they make me shudder, even after all these years.
PMID- 28699466
TI - Work within the limits of your competence.
AB - There is a fine line between working hard to cover staff shortages and being
asked or expected to take on tasks or responsibilities that you aren't confident
or qualified in.
PMID- 28699465
TI - Using the Vessel Health and Preservation framework to enhance vein assessment and
vascular access device selection.
AB - There is a range of risk factors that can lead to peripheral intravenous (IV)
cannula failure, and several failed cannulation attempts can result in the
patient experiencing increased pain, discomfort and delays in receiving IV
therapy. The Vessel Health and Preservation (VHP) framework is a tool that can be
used to improve clinical decision-making and the patient experience in relation
to vascular access and IV therapy. Use of the VHP framework can ensure the right
vein and right vascular access device (VAD) is selected at the right time for
each patient. This article describes how healthcare practitioners can use the VHP
framework to support and enhance vein assessment and VAD selection. It outlines
the various types of VAD available, focusing on short-term peripheral IV
cannulae, which are the most commonly used devices. It also explores the
potential benefits of implementing the VHP framework in clinical areas.
PMID- 28699467
TI - The nurse director role is more challenging than ever.
AB - I was a nurse director for more than 20 years, initially at Royal Brompton
Hospital, then at Royal Brompton and Harefield NHS Foundation Trust. It was a
complex role and an overwhelmingly positive experience. Over the years, however,
much has changed, and today the average tenure is about three years.
PMID- 28699468
TI - Regulator rejects idea that language test is too hard.
AB - The pass level for nurses sitting English language tests is not set too high, a
review by the Nursing and Midwifery Council (NMC) has concluded.
PMID- 28699469
TI - Changes in diet and physical activity cut child obesity.
AB - Making changes to diet, physical activity and behaviour can reduce obesity in
children and adolescents, two separate reviews suggest.
PMID- 28699470
TI - Forging a unique nursing partnership with China.
AB - When members of a London nursing faculty forged a learning partnership with a
Chinese counterpart they likely did not expect to be discussing the benefits of
using Florence Nightingale lamps to decorate hospital walls. But there is nothing
ordinary about the collaboration between King's College London and Nanjing Health
School.
PMID- 28699471
TI - Managers state fears over standards.
AB - The NHS faces 'serious challenges in maintaining standards of care', with senior
managers worried about having the right levels of staff, according to a new
report.
PMID- 28699472
TI - Opinion will be divided on NMC plans, which is why yours counts.
AB - Would you say that nursing is in control of its own destiny? Recent evidence
would suggest otherwise, with politicians, policy wonks and general managers
having a greater say than nurses themselves about the profession's future.
PMID- 28699474
TI - Positive body image grows after exercise sessions.
AB - Women feel better about their body image following 30 minutes of exercise,
according to researchers.
PMID- 28699476
TI - Child Protection, Public Health and Nursing Appleton Jane V and Peckover Sue
(eds) Child Protection, Public Health and Nursing 110pp L19.95 Dunedin Academic
Press 9781780460451 1780460457 [Formula: see text].
AB - The public health remit is undergoing major transformation in the UK, and
specialist community public health nurses are at the forefront of this change.
Much of their work includes child protection, which is the subject of this book.
PMID- 28699478
TI - Long-Term Antithyroid Drug Treatment: A Systematic Review and Meta-Analysis.
AB - BACKGROUND: Several studies have reported inconsistent findings on the advantages
and disadvantages of long-term treatment with antithyroid drugs (ATD). A
systematic review and meta-analysis was undertaken to clarify the numerous
aspects of long-term treatment with ATD. METHODS: Medline and the Cochrane
Library for trials published between 1950 and May 2016 were systematically
searched. Studies containing data for long-term (>24 months) ATD treatment were
included. Summary estimates of pooled prevalence, odds ratio, and weighted mean
difference were calculated with a random effects model. RESULTS: Of 587 related
articles found, six fulfilled the inclusion criteria. Long-term ATD treatment
induced a remission rate of 57% [confidence interval (CI) 45-68%], a rate that
was higher in adults than in non-adults (61% vs. 53%). The rate of complications
was 19.1% [CI 9.6-30.9%], of which only 1.5% were major complications. The annual
remission rate for each year of treatment was 16% [CI 10-27%], which was higher
in adults than non-adults (19% vs. 14%). However, it should be noted that this is
not a true linear correlation, but a positive relationship can be suggested
between time and remission rate. Meta-regression revealed that smoking had a
significant lowering effect on remission rate. CONCLUSIONS: Long-term ATD
treatment is effective and safe, especially in adults, indicating that it should
be considered as an alternative treatment for Graves' disease.
PMID- 28699479
TI - MicroRNAs-based Therapy: A Novel and Promising Strategy for Cancer Treatment.
AB - MicroRNAs are short non-coding RNAs involved in critical biological processes. In
the past decade, the deregulation of miRNAs has been well-documented in a wide
range of human diseases, including cancer. Overexpression and downregulation of
miRNAs affect cellular pathways that contribute to carcinogenesis and tumor
progression. This evidence makes miRNAs a suitable candidate for therapeutic
applications and leads to developing strategies to manipulate their expression.
Consistently, in vitro and in vivo studies show that Let-7, miR-10b, miR-21, miR
34, miR-155 and miR-221 are promising targets to develop miRNAs-based therapy for
human malignancies. The purpose of this review is to discuss the different
approaches that can be used to restore or reduce miRNAs expression in human
cancer and the therapeutic implications.
PMID- 28699480
TI - Adulteration Practices of Psychoactive Illicit Drugs: An Updated Review.
AB - BACKGROUND: Powdery drugs such as cocaine and heroin are frequently adulterated
or diluted predominantly to obtain more doses and to increase the drug dealer's
profits, but also to enhance, to modify or to oppose drug effects. The aim of
this report is to provide an overview of the recent scientific literature on
medicines as well as on new psychoactive substances, used as cutting agents (i.e.
pharmacologically active adulterants) and on the related adverse health effects
on consumers, possibly due to the synergistic effect of the adulterants laced
with substances of abuse. METHOD: A literature search up to January 2017 was
performed on MEDLINE, Scopus and Web of Science and reports and documents of
international agencies or institutions were also searched. RESULTS:
Pharmacologically active substances such as: paracetamol, caffeine,
dextromethorphan, clenbuterol for heroin; levamisole, phenacetine, lidocaine,
hydroxyzine and diltiazem for cocaine; caffeine and phentermine for amphetamine,
have been identified over the years. Furthermore, since cocaine and morphine
(this latter as a precursor of heroin) are both extracted from natural products,
some impurities and minor alkaloids can be present in the final preparation. In
this context, it is worth considering that new psychoactive substances are also
used as cutting agents. CONCLUSION: The wide availability of illicit psychotropic
drugs is the most serious hazard threatening consumers. Indeed emergency
departments are often responsible in evaluating damages caused not only by the
base substance, but also by other eventual compounds added to mimic or antagonize
drug effects or simply dilute the drug amount, with a possible harmful synergic
toxic action.
PMID- 28699481
TI - Editorial: Circulating Biomarkers in Cardiovascular Diseases - A Field of
Theoretical Research or Realistic Clinical Application?
PMID- 28699482
TI - Non-diabetic Glucose levels and Cancer Mortality: A Literature Review.
AB - BACKGROUND: Although diabetes mellitus is a risk factor for cancer, the
relationship of an increased glucose concentration at a non-diabetic glucose
level with cancer mortality is yet to be determined. OBJECTIVE: The aim was to
observe whether an increased glucose concentration and/or glucose intolerance at
the non-diabetic glucose level can predict cancer mortality. METHODS: Population
based prospective cohort studies evaluating cancer mortality at the non-diabetic
level (defined as fasting plasma glucose <7.0 mmol/L and two-hour plasma glucose
<11.1mmol/L following an oral glucose tolerance test) were collected via a PubMed
search with an additional Google scholar search between 1 January 1966 and 31
July 2016. RESULTS: We identified seven studies, which met the defined criteria.
Studies examining fasting/casual states indicated an increase in cancer mortality
with a slight increase in fasting/casual glucose levels in men in particular. Not
all, but some studies using a glucose tolerance test indicated an increase in
cancer mortality with impaired glucose tolerance/prediabetes. Concerning cause
cancer mortality, glucose intolerance states appeared to have an increase in
mortality, particularly due to the stomach, liver and pancreatic cancers.
CONCLUSION: In these studies reviewed, cancer mortality increased in individuals
with an increased glucose concentration and an increased potential was seen in
those patients with glucose intolerance even at non-diabetic glucose levels. The
outcome of these findings is promising and forms the basis for further studies to
directly address the relevance of increased (non-diabetic) glucose and glucose
intolerance as a prognostic indicator of cancer mortality.
PMID- 28699483
TI - Physical Disability and Diabetes Mellitus; Qualitative Exploration of Patients'
Perception and Behavior.
AB - BACKGROUND: Disability is a key indicator implicating both overall morbidity and
success of public health efforts to compress the period of morbidity among
geriatrics for the overall population. Disabilities are more prevalent among
diabetics than among those without diabetes. OBJECTIVE: This study aimed to
determine self-monitoring practices, awareness to dietary modifications and
barriers to medication adherence among physically disabled type 2 diabetes
mellitus patients. METHODS: Interview sessions were conducted at diabetes clinic
Penang general hospital. The invited participants represented three major ethnic
groups of Malaysia (Malay, Chinese & Indians). An openended approach was used to
elicit answers from participants. Interview questions were related to
participant's perception towards self-monitoring blood glucose practices,
Awareness towards diet management, behaviour to diabetes medication and cues of
action. RESULTS: A total of twenty-one diabetes patients between the ages 35 - 67
years with physical disability (P1-P21) were interviewed. The cohort of
participants was dominated by Males (n=12) and also distribution pattern showed
that majority of participants were Malay (n=10), followed by Chinese (n=7) and
rest Indians (n=4). When the participants were asked in their opinion what was
the preferred method of recording blood glucose tests, several participants from
low socioeconomic status and either divorced or widowed denied to adapt
telemontoring instead preferred to record manually. There were mixed responses
about the barriers to control diet/calories. Even patients with high economic
status, middle age 35-50 and diabetes history of 5-10 years were influenced
towards alternative treatments. CONCLUSION: Study concluded that patients with
physical disability required extensive care and effective strategies to control
glucose metabolism.
PMID- 28699484
TI - Immune Response to Native Lipoproteins Induces Visceral Obesity and Aortic Wall
Injury in Rats: The Role of Testosterone.
AB - OBJECTIVES: The underlying mechanism of atherosclerosis and visceral obesity
remains unknown.The purpose of this study was to test the hypothesis that
atherosclerosis and visceral obesity are caused by an immune response to native
plasma lipoproteins, and the atherogenic and adipogenic effects of the antibodies
to native lipoproteins stem from the androgen deficiency that is created.
METHODS: Wistar rats were immunized with native human (nh) low-density (LDL) or
high-density lipoproteins (HDL). Visceral fat, aortic wall structure, and
testosterone levels were studied. RESULTS: Immunization with nhLDL or nhHDL
induced in rats increased visceral abdominal fat and perivascular adipose tissue
volume, the appearance of epicardial fat, and atherosclerosis-like changes in the
aortic wall: accumulation of leucocytes, destruction of the intima, and
disruption of the media structure. Immunized rats produced antibodies to native
plasma lipoproteins, while there was no difference between immunized and adjuvant
injected rats with regard to the level of antibodies to oxidized LDL. The immune
response to nhHDL caused testosterone disturbances, but it is not associated with
visceral obesity and atherosclerosis. CONCLUSION: The immune response to native
lipoproteins is atherogenic and adipogenic and testosterone is not involved in
the atherogenic and adipogenic effects of antibodies to lipoproteins.
PMID- 28699485
TI - Changes in Serum Nampt Levels and Its Significances in Diabetic Nephropathy
Patients-The Potential Role of Nampt in T2DM with Diabetic Nephropathy.
AB - BACKGROUND: Nicotinamide phosphoribosyltransferase(Nampt) has a variety of
biological effects, which can participate in the development of inflammatory
diseases, metabolism diseases and chronic kidney disease, et al. However, the
role of Nampt in T2DM and DN is still controversial. OBJECTIVE: The study aimed
to investigate changes in serum Nampt levels and its significance in diabetic
nephropathy (DN). METHOD: A total of 321 type 2 diabetes (T2DM) were divided into
normal albuminuria group (NA, n=110), microalbuminuria group (MA, n=106) and
large amount of albuminuria group (LA, n=105). 105 healthy persons were selected
forming the control group (NC, n=105).; 118 T2DM without insulin therapy were
screened out as the non-insulin therapy group (NIT.; n=116). Serum Nampt and
interleukin (IL)-1beta were measured by enzyme-linked immunosorbent assay. The
relationships among the variables were analyzed by Pearson correlation analysis
and Stepwise multiple regression analysis. RESULTS: Serum Nampt and IL-1beta in
the LA group were significantly higher than other groups, and they were higher in
MA than in the NA group (P<0.05). Serum Nampt was positively correlated with IL
1beta and urinary albumin-to-creatinine ratio (UACR) (P <0.01), and IL-1beta and
UACR were independent relevant factors affecting Nampt. Serum Nampt was
positively correlated with insulin resistance (HOMA-IR) but negatively correlated
with the quantitative insulin sensitivity check index (QUICKI) (P <0.01) in the
NIT group. CONCLUSION: We indicated that serum Nampt and IL-1beta were increased
accompanied by the increased UACR and the association between Nampt and insulin
resistance and beta-cell function in T2DM with different UACRs.
PMID- 28699487
TI - Mixed Matrix Method Provides A Reliable Metabolite Exposure Comparison for
Assessment of Metabolites in Safety Testing (MIST).
AB - BACKGROUND: The regulatory guidances on metabolites in safety testing (MIST) by
US Food and Drug Administration (FDA) and International Conference on
Harmonisation (ICH) describe the necessity to assess exposures of major
circulating metabolites in humans at steady state relative to exposures achieved
in nonclinical safety studies prior to the initiation of large scale clinical
trials. This comparison can be accomplished by measuring metabolite
concentrations in animals and humans with validated bioanalytical methods.
However, bioanalysis of metabolites in multiple species and multiple studies is
resource intensive and may impact the timelines of clinical studies. METHOD: A
simple, reliable and accurate method has been developed for quantitative
assessment of metabolite coverage in preclinical safety species by mixing equal
volume of human plasma with blank plasma of animal species and vice versa
followed by an analysis using LC-SRM or LC-HRMS. Here, we explored the
reliability and accuracy of this method in several development projects at
Genentech and compared the results to those obtained from validated bioanalytical
methods. RESULTS: The mixed-matrix method provided comparable accuracy (within +/
20%) to those obtained from validated bioanalysis but does not require authentic
standards or radiolabeled compounds, which could translate to time and resource
savings in drug development. CONCLUSION: Quantitative assessment of metabolite
coverage in safety species can be made using mixed matrix method with similar
accuracy and scientific rigor to those obtained from validated bioanalytical
methods. Moving forward, we are encouraging the industry and regulators to
consider accepting the mixed matrix method for assessing metabolite exposure
comparisons between humans and animal species used in toxicology studies.
PMID- 28699486
TI - Stress, Depression, Resilience and Ageing: A Role for the LPA-LPA1 Pathway.
AB - BACKGROUND: Chronic stress affects health and the quality of life, with its
effects being particularly relevant in ageing due to the psychobiological
characteristics of this population. However, while some people develop
psychiatric disorders, especially depression, others seem very capable of dealing
with adversity. There is no doubt that along with the identification of
neurobiological mechanisms involved in developing depression, discovering which
factors are involved in positive adaptation under circumstances of extreme
difficulty will be crucial for promoting resilience. METHODS: Here, we review
recent work in our laboratory, using an animal model lacking the LPA1 receptor,
together with pharmacological studies and clinical evidence for the possible
participation of the LPA1 receptor in mood and resilience to stress. RESULTS:
Substantial evidence has shown that the LPA1 receptor is involved in emotional
regulation and in coping responses to chronic stress, which, if dysfunctional,
may induce vulnerability to stress and predisposition to the development of
depression. Given that there is commonality of mechanisms between those involved
in negative consequences of stress and in ageing, this is not surprising,
considering that the LPA1 receptor may be involved in coping with adversity
during ageing. CONCLUSION: Alterations in this receptor may be a susceptibility
factor for the presence of depression and cognitive deficits in the elderly
population. However, because this is only a promising hypothesis based on
previous data, future studies should focus on the involvement of the LPA-LPA1
pathway in coping with stress and resilience in ageing.
PMID- 28699489
TI - Synthesis and Evaluation of Antioxidant and Cytotoxicity of the N-Mannich Base of
Berberine Bearing Benzothiazole Moieties.
AB - BACKGROUND: Berberine, a quaternary ammonium salt from the protoberberine group
of benzylisoquinoline alkaloids has drawn high attention for its several
biological potencies. OBJECTIVE: To furnish new rationalized derivatives based on
berberine core which can deliver promising antioxidant and cytotoxic activities.
METHOD: The N-Mannich base of an isoquinoline alkaloid, berberine, bearing
substituted benzothiazole moieties was obtained. Novel synthesized analogues were
in vitro screened for antioxidant efficacy toward 2,2-diphenyl- 1-picrylhydrazyl
(DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) free
radicals and in vitro cytotoxicity towards cervical cancer cell lines (HeLa and
CaSki), an ovarian cancer cell line (SK-OV-3) and human renal cancer cell line
(Caki-2). Cytotoxicity of the compounds toward normal cell lines was examined
using the Madin-Darby canine kidney (MDCK) non-cancer cell line. RESULTS:
Analogues bearing a methoxy functional group (5e), acid functionality (5c), and a
cyano group (5m) showed remarkable radical scavenging potential in DPPH and ABTS
bioassays. Potent cytotoxicity exhibited by berberine against the HeLa cell line
was attributable to the presence of a 2-aminobenzothaizole moiety (5a) and its 6
chloro congener (5g) on the berberine core, and the 6-cyano group (5m) on the
benzothiazole ring revealed strong sensitivity for the CaSki cell line, whereas
subjected scaffolds demonstrated diminished activity against the SK-OV-3 cell
line. In addition, the compound with a 2-aminobenzothaizole moiety (5a), compound
with methoxy functional group (5e) and compound with cyano group appeared with
the most significant cytotoxicity effect in Caki-2 cell line. Their structures
have been elucidated by FT-IR, 1H NMR, 13C NMR, and elemental analyses (CHN)
essential research. CONCLUSION: N-Mannich bases of berberine were efficiently
generated utilizing pharmacologically diverse substituted 2-aminobenzothiazole
entities and final compounds were found remarkably active in antioxidant and
cytotoxic assay. Hence, such types of compounds can be further studied or
rationalized in future drug discovery studies.
PMID- 28699488
TI - A Review of Interventions to Improve Enrolment and Adherence to Cardiac
Rehabilitation Among Patients Aged 65 Years or Above.
AB - PURPOSE: This review provides an overview and quality assessment of existing
interventions, assessing the intervention types that are most effective at
increasing enrolment and adherence to cardiac rehabilitation in older patients
aged >=65 years Methods: The review of the literature was performed using
electronic databases to search for randomised controlled trials that aimed to
increase enrolment and/or adherence to cardiac rehabilitation in older patients
aged >=65 years. The main key words were cardiac rehabilitation, enrolment,
adherence and older patients. Studies were included if; (1) the intervention
targeted improving enrolment and/or adherence to at least one of the following
components of the cardiac rehabilitation programme: exercise, education or
maintaining lifestyle changes; (2) assess the effectiveness of an intervention on
increasing enrolment and/or adherence to a cardiac rehabilitation programme or
any of its components; (3) include measures for assessing enrolment and/or
adherence to a cardiac rehabilitation programme or any of its components; (4) the
study included patients with a mean age of >=65 years who were deemed eligible to
participate in a cardiac rehabilitation programme. Included studies could be
published in any language and there were no date restrictions for included
studies. Studies focusing on pharmaceutical adherence were not included for the
purpose of this review. RESULTS: Seven studies were included, with four
investigating enrolment (1944 participants) and three assessing adherence to
intervention programmes (410 participants). Three studies (1919 participants)
reported higher enrolment to cardiac rehabilitation in the intervention group.
Two studies that reported increases in enrolment to cardiac rehabilitation were
deemed to have an unclear or high risk of bias. All three studies (410
participants) reported better adherence to cardiac rehabilitation in the
intervention group when compared to the control group. Two studies that reported
better completion of cardiac rehabilitation were deemed to have an unclear or
high risk of bias. No formal meta-analysis was conducted due to the observed
multiple heterogeneity among outcome measures, the low number of included studies
and variability in study designs. CONCLUSION: This review found only weak
evidence to suggest that interventions can increase enrolment or adherence to
cardiac rehabilitation programmes for patients aged >=65 years, therefore no
practice recommendations could be made and further high-quality research is
needed in this population group.
PMID- 28699490
TI - Design and Discovery of Novel Quinoxaline Derivatives as Dual DNA Intercalators
and Topoisomerase II Inhibitors.
AB - : Backgroun/Methods: In attempt to develop new potent anti-tumor agents, a series
of quinoxaline derivatives was designed and synthesized. The novel compounds were
tested in vitro for their anti-proliferative activities against HePG-2, MCF-7 and
HCT-116 cell lines. Additionally, DNA binding affinities as well as DNA-top II
inhibitory activities of the synthesized compounds were investigated as potential
mechanism for anticancer activity. Compounds 13, 15, 16 and 19 exhibited good
cytotoxicity activities against the three cell lines (IC50 ranging from 7.6 to
32.4 uM) comparable to that of doxorubicin (IC50 = 9.8 uM). RESULTS:
Interestingly, the results of DNA binding and DNA-top II inhibition assays were
in agreement with those of the cytotoxicity tests, where the most potent
anticancer compounds showed good DNA binding affinities (IC50 ranging from 25.1
to 32.4 uM) and DNA-top II inhibitory activities (IC50 ranging from 6.4 to 15.3
uM) comparable to those of doxorubicin (IC50 = 28.1 and 3.8 MUM, respectively).
Furthermore, molecular docking studies were carried out for the new compounds in
order to investigate their binding pattern with the prospective target, DNA-top
II complex (PDB-code: 3qx3).
PMID- 28699491
TI - A Case of Pantoprazole Anaphylaxis with Cross Reactivity to All Proton Pump
Inhibitors: Finding a Safe Alternative.
AB - BACKGROUND: Hypersensitivity reactions due to Proton pump inhibitors (PPIs ) are
rare, and further anaphylaxis to a PPI with cross-reactivity to all commercially
available PPIs is very rare. OBJECTIVE: To present a case of anaphylaxis to
pantoprazole with cross-reactivity to all commercially available PPIs. METHODS:
Skin prick tests (SPTs), intradermal tests (IDTs) and oral provocation tests
(OPTs) were performed with available PPIs according to the method described in
previous studies. RESULTS: All tested PPIs except lansoprazole were positive on
skin tests either SPT or IDT. The patient was challenged with lansoprazole at
increasing doses (7.5 mg, 15 mg, 30 mg capsule) every 60 minutes and she reacted
with urticaria to 52.5 mg cumulative dose of lansoprazole. She could tolerate
ranitidine and famotidine tablets via OPT. CONCLUSION: In our best knowledge, our
case was the first case in this regard and that points the possibility of all
cross-reactive pattern in patients with pantoprazole anaphylaxis and the
importance of a thorough drug allergy work-up for finding safe alternatives. H2
receptor antagonists are used as safe alternatives in cases with PPI
hypersensitivity.
PMID- 28699492
TI - Adverse Drug Reactions in Critical Care Settings: A Systematic Review.
AB - BACKGROUND: The prevalence of adverse drug reactions is reported to be high in
critical care units. We conducted a systematic review to study the prevalence,
drugs implicated, preventability, predictability, severity and determinants of
adverse drug reactions in critical care settings. METHODS: We searched MEDLINE,
EMBASE, PROQUEST and OVID (January 1995 to June 2015) using pre-specified
appropriate medical subject heading terms. Of 1552 studies, 34 studies were
included for data extraction and synthesis. RESULTS: Overall, the prevalence of
adverse drug reactions was 0.3% to 17% in paediatric intensive care units and
4.5% to 34.1% in adult intensive care units. The highest prevalence reported
among critical care settings was 117.4 per 1000 patient days. The most common
drug classes implicated were antimicrobials in the medical intensive care units,
cardiovascular drugs and anticoagulants in the coronary care units, and
analgesics and sedatives in the surgical care units. The prevalence of fatal and
severe adverse drug reactions ranged from 0.9 to 19% and 5.7 to 28.6%
respectively. The predictable and preventable adverse drug reactions ranged from
74.3 to 90.2% and 8.6 to 62.8% respectively. Only 8 studies reported patient
outcomes. About 5.6% to 25.5% of patients died. CONCLUSION: There is wide
variation in prevalence, characteristics and drug classes implicated in the
occurrence of adverse drug reactions by type of intensive care unit. Findings of
this study would help health care professionals to optimise pharmacotherapy in
critical care settings.
PMID- 28699494
TI - The Small Molecules Targeting Ubiquitin-Proteasome System for Cancer Therapy.
AB - BACKGROUND & AIM: The ubiquitin-proteasome system (UPS) is the major pathway for
degrading the intracellular proteins. The 2004 Nobel Prize in Chemistry was
awarded to Rose, Hershko, and Ciechanover to highlight the fundamental importance
of UPS. METHOD & RESULTS: The alterations in this process have been shown to
contribute to the cancer progression. Hence, UPS has become a popular target for
developing chemotherapeutics against tumours. The application of bortezomib
showed high efficiency in treating haematological malignancies by interfering
with UPS activity. Many compounds are being screened and evaluated in recent
pharmacological advances, either as single agents or in synergy with other drugs,
and more to be revealed. CONCLUSION: In the present review, we exhibit the
crucial ingredients involved in UPS and discuss the current situation of small
molecules targeting various components of ubiquitination pathway in cancer
treatment.
PMID- 28699493
TI - Hallucinations Associated with Topiramate Therapy: A Case Report and Review of
the Literature.
AB - BACKGROUND: Topiramate is a medication that is approved as both monotherapy and
adjunctive treatment of seizure disorder in adults and adolescents. It is also
approved for migraine prophylaxis. It has been associated with many side effects,
including weight loss and the development of renal stones. It has also been
associated with various central nervous system side effects such as dizziness,
nervousness, parasthesias, and fatigue. Less commonly, it has been associated
with the development of psychotic symptoms such as hallucinations. OBJECTIVE: To
describe the relationship between the administration of topiramate and the
development of hallucinations in this patient. METHODS: We will now present the
case of a 32-year-old man who developed auditory hallucinations after initiating
a relatively low dose of topiramate (25mg twice daily) for the treatment of
chronic pain. We will review the prior cases of topiramate induced
hallucinations, and discuss how these cases compare to the case we have
described. We will review the treatment of these hallucinations. RESULTS: In this
case, there was a close temporal relationship between the initiation of
topiramate and the onset of auditory hallucinations. CONCLUSION: This case
supports the previous reports describing the association between the use of
topiramate and the developmenrt of hallucinations. Although the average daily
topiramate dose associated with the development of hallucinations in previously
reported cases was 150 mg in women and 181 mg in men, hallucinations can occur at
lower doses (as low as 50 mg daily) as well.
PMID- 28699495
TI - Dietary Phytochemicals and Endrocrine-related Activities: An Update.
AB - Phytochemicals are non-nutrient bioactive compounds occurring in plants and food,
which possess the capacity to modulate one or more metabolic processes or
pathways in the body, resulting to health benefits and promotion of well-being.
The interest of the scientific community continues to grow, powered by
progressive research efforts to identify properties and potential applications of
bioactive substances, and coupled with public interest and consumer demand.
However, the natural derivation of these compounds is not a feature of
harmlessness, over that of therapeutic efficacy, to which is also added the
absence of post-marketing monitoring which does not allow to evaluate the
occurrence of adverse effects related to the use of their related products. The
literature is particularly rich of studies concerning phytochemicals as
environmental estrogens, which result in infertility, reproductive abnormalities,
and tumors but also in some endocrine-related health effects. Nevertheless,
further studies have been performed to better understand the bioavailability,
pharmacokinetics and mode of action of these compounds which seems to go beyond
their ability to bind to oestrogen receptors and either stimulate or inhibit the
activity of endogenous oestrogens, highlighting new interesting target molecules
and signaling pathways. The present review summarizes the latest developments and
knowledge concerning the assessment of endocrine activities of dietary
phytochemicals focusing on pharmacological aspects.
PMID- 28699496
TI - Up Scaling Strategies to Improve the Industrial Production of Bacitracin at
Largescale.
AB - BACKGROUND AND OBJECTIVE: Bacitracin was discovered and named after a 7 year old
American girl, Margaret Tracey in 1943 as Bacillus was isolated from her wounds.
Bacillus licheniformis is usually present in soil and bird feathers. This
bacterium is most commonly present around back plumage and chest of birds. There
are different types of bacitracin but the one most potent is Bacitracin A.
Bacitracin induced proteins are localized in bacterial membrane. Production of
antibiotic initially stopped, resumed by induction of bacitracin induced protein
but after few mitotic divisions microbes reverted to their vulnerable state.
Induction of protein ceases after 4th hour of stationary phase. Immobilization is
necessary for economic, process convenience and stability of the cell. Moreover,
immobilization increases the ability of the cell to produce product in high
quantity. CONCLUSION: Maximum production of antibiotic was noted at pH 8 after 4
hours of incubation at various glucose concentrations in shake flask fermentation
at 30 degrees C when immobilized in polyacrylamide gel. Increase in antibiotic
activity was also found with increase in use of cells. Efforts have been made to
alter heterocyclic metal binding subunit of bacitracin by synthesizing
heterocyclic building blocks that can be coupled to linear decapeptide and
consequently cyclization by PCPTE biodomain of bacitracin. Derivatives of
bacitracin showed antimicrobial activities indicating the possibility of
overcoming existing limitations just by altering their heterocyclic subunit.
Bioactivity and stability can be increased by modifying peptide backbone of
compounds.
PMID- 28699497
TI - Quantitative Structure-Activity Relationships of Aquatic Narcosis: A Review.
AB - BACKGROUND: Prior estimation of toxicity of each and every, existing and yet to
be synthesized chemicals is a must to elude their adverse effect on the
environment. Experimental determination of such parameters is time consuming,
cost effective and above all, it demands the sacrifice of many vertebrates. At
this end, the REACH regulations advocate for the use of non-testing predictive
methods such as read-across, weight-of-evidence and QSAR (quantitative structure
activity relationship) techniques. Among these methods, QSAR is found to be the
best as it is based on molecular structure only. The descriptors used in deriving
the model in QSAR vary according to the nature of the narcotics as well as the
species used for. The success of a model in predicting the toxicity of a narcotic
purely depends on the type of descriptors selected that explains the structural
features closely related to the property under study. In this review, we have
focused on the different types of descriptors and QSAR models used to explain the
narcosis phenomenon. METHODS: Literature was scanned for acute toxicity of
chemicals on species like tadpoles, protozoa, planktonic crustaceans, and small
fishes like million fish, rainbow fish etc. from different sources. The toxicity
and toxicants were classified considering their polarity and specific
interactions of the compounds. Due to complex nature of the substrate, the
mechanism of action of toxicant is uncertain. However, the overall results
obtained from the biological study have been subjected to QSAR studies to obtain
various models, which can provide some ideas on the mode of toxicological action.
Different types of molecular descriptors derived both experimentally and
theoretically have been used in the QSAR studies. RESULTS: Mostly biochemicals
have a specific signature on oil/water partition (Ko/w, P), which is the crux in
biological activity. Accordingly, the toxicological activities have good
correlations with log P. Addition of some more structural descriptors improves
the structure-toxicity relationship. Among these, electronic descriptors like
EHOMO, ELUMO and DeltaE derived from molecular orbitals have been used in the
QSAR. ELUMO describing the energy of excited species of the molecule is found to
be the most suitable one. Other molecular descriptors used in the QSAR include
constitutional, topological and Abraham's solute descriptors. The models derived
from the QSAR studies were found to be highly significant to predict the
toxicology as well as to throw light on the mechanism. CONCLUSION: The best
descriptor for aquatic narcosis is the KO/W or P. Addition of an electronic
parameter (ELUMO) improves the QSAR to some extent. However, substitution of
ELUMO by other class of molecular descriptors has also some statistical
significance. To have a global QSAR model, in addition to P, some more
appropriate descriptors are to be derived either experimentally or theoretically,
latter being the more cost effective and easy in derivation.
PMID- 28699498
TI - Is the Addition of a Polyol to Hyaluronic Acid a Significant Advance in the
Treatment of Osteoarthritis?
AB - Viscosupplementation with intra-articular injections of hyaluronic acid is
recommended as a second line treatment for knee OA, after failure of non
pharmacological modalities and usual pain killers. Nevertheless there are still
controversies regarding clinical relevance of its effects. Research is looking
for the best way to improve the performance of viscosupplementation in order to
obtain a faster, longer-lasting and more pronounced effect. Antioxidants have
been assessed in combination with hyaluronic acid because the injected
hyaluronate is rapidly degraded by the reactive oxygen species, present in large
amounts in the OA synovial fluid, limiting its residence time into the joint.
Sorbitol and mannitol which have intrinsic free radical scavenger properties have
been the most studied antioxidants. Sodium hyaluronate and polyols develop
together a complex based on a dense network of hydrogen bonds which do not modify
the visco-elsatic properties of hyaluronic acid. The oxygen free radicals
neutralization by mannitol has been proven to delay the degradation of both
linear and cross-linked HA in several in vitro models of oxidative stress. The
antioxidant effect of these polyols may also play a role in accelerating onset of
analgesia, as demonstrated in a double blind controlled trial comparing a
mannitol-modified viscosupplement to regular hyaluronic acid. The addition of
mannitol and sorbitol to hyaluronic acid does not alter the safety and local
tolerability. In summary, adding a polyol to hyaluronic acid may improve the
effects of viscosupplementation by reducing the rate of degradation of HA leading
to a faster effect on pain relief without increasing the risk of adverse effect.
PMID- 28699499
TI - Effectiveness of Argan Oil Consumption on Knee Osteoarthritis Symptoms: A
Randomized Controlled Clinical Trial.
AB - BACKGROUND: Knee osteoarthritis (KOA) is a common chronic degenerative disorder.
It causes joint pain, walking difficulties and a decline in general physical
function. Many pain drugs and treatment modalities can be prescribed for KOA.
Among traditional medicines in Morocco, Argan oil has been used in the treatment
of knee osteoarthritis to reduce pain and improve physical activity, though there
have been no medical-based evidence for such treatment. Argan oil is known to
have anti-oxidant and lipid modulatory properties due to its content of many
substances, such as tocopherols, phytosterols, saturated and unsaturated fatty
acids. OBJECTIVES: This study was undertaken in order to investigate the effect
of daily consumption of culinary argan oil on KOA symptoms. PATIENTS AND METHODS:
We conducted a randomized controlled clinical trial on patients with KOA
according to the American College of Rheumatology (ACR) criteria. Patients were
divided into 2 groups: argan oil group who received argan oil to be consumed
every morning (30 ml per day) for 8 weeks and control group with no treatment.
Clinical assessment before and after 8 weeks study was performed by several tests
such as the Visual Analogue Scale (VAS) for pain, walking perimeter, the Western
Ontario and McMaster Universities osteoarthritis index (WOMAC), and the Lequesne
index. RESULTS: The study included 100 patients. 51 patients were randomly
assigned to argan oilgroup while 49 patients were randomly assigned to control
group with no treatment. Mean age of our patients was 58.24 +/- 7.2 years, with a
majority of women (93%). Following 8 weeks of argan oil consumption, argan oil
group had a very significant decrease of VAS for pain (p< 0.0001), with a
significant decrease in WOMAC pain index (p < 0.0001), and improvement of WOMAC
function index (p < 0.0001). Lequesne index (p < 0.0001) as well as walking
distance (p =0,002) significantly improved. When data of argan oil group were
compared to those of control group, we found statistically significant
differences in all the above measured parameters: VAS of pain (P=0,02), WOMAC
pain (p<0,0001), WOMAC function (p<0,0001), walking distance (p=0,001) and
lequesne index (p<0,0001). CONCLUSION: Patient's consumption of argan oil seems
to be safe and efficacious in improving clinical symptoms of KOA.
PMID- 28699500
TI - Cell-derived Exosomes as Promising Carriers for Drug Delivery and Targeted
Therapy.
AB - Exosomes are small vesicles that are secreted by various types of cells, known to
mediate signal transduction between cells. During recent years, novel carriers
for the delivery of targeted drugs, chemotherapy drugs and RNAs are under
development, which is believed to be beneficial for patients. Considering issues
of drug nano-formulations in bloodstream, such as nano-toxicity and rapid
clearance by mononuclear phagocyte system, exosomes derived from either patient's
cells or bodyfluids, seem to be an optimal option. This review presents the
current patterns of drug-loaded into exosomes and discusses how exosomes were
reconstructed for targeted therapy. Loading either exosomes directly or their
donor cells is an alternative, including incubation, electroporation,
transfection of exosomes or transfection, incubation, activation of the parent
cells. To solve the low efficiency of cargo loading into exosomes, protein
loading via optically reversible protein-protein interaction can realize a novel
exosomal protein carrier. In addition, targeted therapeutics with exosomes is
achieved by three means, via adding targeting peptides into the surface of
exosomes, by transferring specific genes within exosomes into tumors to establish
a therapeutic target and, lastly, by targeting at exosomes containing tumor
associated antigens. Nevertheless, purification and mass production of exosomes
need further exploration, as well as more approaches were applied to targeted
therapy. Therefore, exosomes could serve as an effective tool for drug delivery
and targeted therapy.
PMID- 28699501
TI - The Role of Oxidative Stress Modulators in Breast Cancer.
AB - BACKGROUND: Latest data from International Agency for Cancer Research shows that
breast cancer is the leading cancer site in women and is the leading cause of
death among female cancers. Induction of reactive oxygen species (ROS) and
oxidative stress as a consequence of impaired balance between prooxidants and
antioxidants are suggested to be involved in induction and progression of breast
cancer. Cancer cells are found to exhibit higher levels of ROS compared to normal
cells. However increased antioxidant defence which balances the oxidative status
within the cancer cells suggests that high ROS levels may prevent tumorigenesis
via various mechanisms. These contradictory roles of ROS and oxidative stress in
breast cancer let scientists investigate potential oxidative stress modulators as
anticancer strategies. CONCLUSIONS: In the present review we address the
mechanisms of ROS production in breast cancer cells, the role of impaired
oxidative status as well as the benefits of introducing oxidative stress
modulators in therapeutic strategies in breast cancer. This review is focusing
more on melatonin which we have been working on during the last decade. Our data,
in accordance with the literature, suggest an important role for melatonin in
breast cancer prevention and adjuvant therapy.
PMID- 28699502
TI - Chronic wounds: Innovations in diagnostics and therapeutics.
AB - One of the major global health issues is the existence of chronic wounds. Chronic
wounds are wounds that show a delayed, or even failed, healing process. The
healing process often stagnates in the inflammatory phase or proliferative phase.
Since traditional treatment methods have shown to be of limited effectiveness in
chronic wound care, the focus has shifted to increase the knowledge of the wound
healing process and the deficiencies encountered in chronic wounds. This
increased knowledge has provided the opportunity for development of new
diagnostics and therapeutics in chronic wound care that detect and treat specific
deficiencies instead of one common treatment for all chronic wounds. This mini
review aims to provide an overview of the current knowledge about the wound
healing process and its deficiencies in chronic wound care. In addition, some
promising diagnostic and therapeutic innovations will be highlighted.
PMID- 28699503
TI - Metabolic Syndrome: Sex-Related Cardiovascular Risk and Therapeutic Approach.
AB - BACKGROUND: The metabolic syndrome (MetS) is a cluster of risk factors for the
development of cardiovascular diseases (CVD) and type 2 diabetes (T2DM).
According to several meta-analyses, it has been shown that the cardiovascular
(CV) risk conferred by the MetS is higher in women in comparison with men. There
are many possible reasons to explain a higher CV risk in women with MetS: the
most important differences can be attributed to distribution of central
adiposity, lipid profile and hormones, but also differences in platelet biology
and biochemistry play an important role. METHODS: In this article we performed a
research using PubMed database reviewing the evidence in literature (in
particular clinical trials and meta-analyses) or lack of evidence/ biased
information regarding the distribution by gender of MetS components and
associated CV risk and we intended to provide a consequent gender perspective to
the treatment of MetS and CV risk. RESULTS: Twenty-three papers were evaluated
searching for sex differences in the prevalence of MetS and CV risk. We also
identified fifty-six papers dealing with sex differences in adiposity, insulin
resistance and hormonal regulation. In terms of gender-specific expression of
MetS in chronic disease we analyzed thirty-one papers focusing the attention on
non-alcoholic fatty liver disease, polycystic ovarian syndrome, gestational
diabetes mellitus, rheumatoid arthritis and HIV infection. We also evaluated
twenty papers focusing on gender differences in platelet biology/reactivity and
thirty-three papers on the gender approach in the treatment of MetS. The CV risk
conferred by MetS segregates differently according to gender; differences between
sexes may depend on the different representation of MetS components, gender
specific genetic, acquired metabolic and hormonal milieu and finally on a
differential interaction between known risk factors and genderspecific
properties, resulting in different degrees of pathophysiological events
eventually leading to atherothrombosis. Regarding a potential sex-related
therapeutic approach, even if gender-related differences exist in the
pharmacokinetics of drugs for differences in body composition, plasma protein
binding, metabolizing enzymes and difference in excretion characteristics, we
have to acknowledge that women are under-represented in clinical trials, thus
preventing from adequately challenging the efficacy and safety of drugs in this
gender. CONCLUSION: While ncreasing knowledge exists regarding pathophysiological
differences between genders in the prevalence of MetS components as well as in
the associated cardiometabolic risk, underrepresentation of women in clinical
trials and underutilization of guideline therapy, for instance in women with
ischemic heart disease, largely flaw the interpretation of epidemiological and
clinical evidence. Efforts should be undertaken to fight the so-called "Yentl
syndrome" and to promote gender-specific drug trials, or at least studies where
subgroup analyses by gender are pre-specified.
PMID- 28699504
TI - Recent Advances on Cellulose-Based Nano-Drug Delivery Systems: Design of Prodrugs
and Nanoparticles.
AB - Cellulose being the first abundant biopolymers in nature is playing an increasing
role as a carrier material in the biomedicine field. Compared with other
materials, cellulose has its own advantages, including rich in resources, good
thermal and chemical stability, high hydrophilicity, and excellent
biocompatibility, etc. These fascinating properties have made cellulose a real
potential material to create nano-drug delivery systems. However, the structure
of pure cellulose caused some inherent shortcomings, for instance, bad plasticity
and dimensional stability, poor solubility in ordinary solvents, and lack of
antibacterial activity. Therefore, it is indispensable to modify the morphology
and microstructure of cellulose. This review presents some remarkable recent
advances on the drug delivery applications of cellulose-based prodrugs and
nanoparticles. Various methods employed for the functionalization,
pharmacodynamic actions and applications are covered.
PMID- 28699505
TI - Tackling Chronic Pain and Inflammation through the Purinergic System.
AB - The purinergic system is composed of purine and pyrimidine transmitters, the
enzymes that modulate the interconversion of nucleotides and nucleosides, the
membrane transporters that control their extracellular concentrations, and the
many receptor subtypes that are responsible for their cellular responses. The
components of this system are ubiquitously localized in all tissues and organs,
and their involvement in several physiological conditions has been clearly
demonstrated. Moreover, extracellular purine and pyrimidine concentrations rise
several folds under pathological conditions like tissue damage, ischemia, and
inflammation, which suggest that this signaling system might contribute both to
disease outcome and, possibly, to its tentative resolution. The complexity of
this system has greatly impaired the clear identification of the mediators and
receptors that are actually involved in a given pathology, also due to the often
opposite roles played by the various receptor subtypes. Nevertheless, this
knowledge is fundamental for the possible exploitation of these molecular
entities as targets for the development of new pharmacological approaches. In
this review, we aim at highlighting what is currently known on the role of the
purinergic system in various pain conditions and during inflammatory processes.
Although some confusion may arise from conflicting results, literature data
clearly show that targeting specific purinergic receptors may represent an
innovative approach to various pain and inflammatory conditions, and that new
purine-based drugs are now very close to reach the market with these indications.
PMID- 28699506
TI - Natural or Plant Products for the Treatment of Neurological Disorders: Current
Knowledge.
AB - BACKGROUND: In recent decades, complementary and alternative medicine (CAM) has
become very popular in the treatment of several chronic diseases. Natural
products as one of the CAM modalities offer potential opportunities to discover
lead compounds for novel drug development. The use of CAM or natural products in
the prevention of neurodegenerative diseases is comparatively a newer area.
METHOD: A structured online literature search for peer-reviewed research articles
was conducted on the PubMed, Europe PMC, Medline and Google Scholar portals,
using phrases: natural products for neurologic disorders, phytomedicine for
neurodegenerative diseases, natural therapeutics for neurological symptopms etc.
Results: The retrieved data showed the natural therapeutics with anti-oxidative
and anti-inflammatory salutations evidently plays a crucial role in protecting
neurons. Of these, the most promising are caffeine, trigonelline, shogaol,
curcumin, resveratrol, baicalein, wogonin, ginsenosides, tanshinones,
withanolides, picrosides, parthenolide, cannabinoids, Devil's claw and white
willow bark, including Chinese formulations Renshen Shouwu and Shengmai San.
Though several herbs and their active ingredients have been studied in laboratory
and clinical settings, only a few have been investigated for their molecular
mechanisms of action. Notably, despite the promising and safe therapeutic
benefits of CAM/herbal medicines, there exists a possible risk when combining
them with prescription drugs. As a result, many drugs have shown changes in blood
pressure, hepatotoxicity, seizures etc. when combined with certain herbs.
CONCLUSION: Certainly, extensive work is needed to make sure that patients should
take a regimen of protective and restorative therapy under an experienced
healthcare professional. This article updates on the current knowledge of
promising natural products used in neurological disorders.
PMID- 28699507
TI - Quinolones and Fluoroquinolones to Treat Salmonella Typhimurium: A Review of
Metabolism and Pharmacokinetics.
AB - BACKGROUND: Salmonella enterica serovar typhimurium is the most important
serotype of Salmonella transmitted from animals to humans in most parts of the
world. They are associated with an estimated 1 million deaths annually.
Quinolones, an important class of broad-spectrum antimicrobials, have been
utilized as a treatment option for salmonellosis for over 40 years. Despite the
number of available quinolone agents, many of them failed in the clinical stage
and never make it to FDA approval. Despite considerable evidence reveals the
importance of different drug discovery process of S. typhimurium, there are no
systematic review outlining the pharmacokinetic and pharmacodynamic parameters of
quinolones. Keeping this in mind, the present study aims to provide a systematic
review on metabolism and pharmacokinetics of different quinolones. METHODS:
Information from all relevant bibliographic databases was used. Additionally, the
recent journal articles and textbooks were searched manually in the preparation
of this review article. RESULTS: A total of 136 journal articles and textbooks
were included in the preparation of the review. Majority of research articles
defines about the metabolism, pharmacodymanics and pharmacokinetics of different
quinolones. Twenty eight papers outlined about the mechanism and challenges faced
by the quinolones and fluoroquinolones. Finally, information on drug
interactions, adverse effects and drug resistance of quinolones and
fluoroquinolones were supported with forty two research articles. Note that the
importance of computational biology in the field of drug discovery was also
addressed with appropriate literatures. CONCLUSION: Overall, the findings of this
review highlight the importance of pharmacokinetic profiling of different
quinolones in developing novel drugs to overcome drug resistance in the near
future.
PMID- 28699508
TI - Recent Development and Future Prospects of Plant-Based Vaccines.
AB - BACKGROUND: Growing world population and continuous disease emergence have
invited the development of more efficient new vaccines against a range of
diseases. Conventional vaccines are being wildly used in the world but their
production requires higher cost, more time and better infrastructure. Thus, the
idea of plant-based edible vaccine technology has emerged and showed promising
results with strong and effective protection against many diseases. Plants have
been utilized since more than two decades as pharmaceuticals against many
diseases. METHODS: Plant-based technology has great potential to express genes
and produce clinically important compounds in the desired tissue. Plant
biotechnology has played important role in the production of pharmaceutical
compounds like vaccines, antibodies, antigens, sub-units, growth hormones and
enzymes by utilizing genetic modification. It has also been opened a new approach
for developing an edible vaccine as an oral delivery. RESULTS: Edible vaccines
have been shown to induce both mucosal as well as systemic immunity. Currently,
many pharmaceuticals proteins as an edible vaccine have been developed in
different plant expression systems and evaluated against various life-threatening
diseases and some of them have reached advanced phase of the clinical trial and
exhibited promising results. CONCLUSION: In this review, we have discussed about
the molecular pharming, edible vaccines, plant base technology and current status
of developed edible vaccines in the different plant tissue expression system,
mechanism of action and clinical applications with clinical trials stage,
significance, requirements, advantage and disadvantage of edible vaccines.
PMID- 28699509
TI - Combination of Multifunctional Nanoparticles and Interventional Techniques Makes
Each Other Going Further in the Field of Cancer Treatment.
AB - BACKGROUND: Nano-oncology and interventional oncology are both rapidly emerging
fields in cancer therapies. Synergistic combination of the both fields offers
drastic improvements in performance and efficacy of cancer killing agents.
OBJECTIVE: This review is to overview the studies focusing on these two crossing
fields and to give an overlook of their future development. Interventional
techniques such as selective arterial catheterization, irreversible
electroporation (IRE) and radiofrequency ablation (RFA) dramatically enhanced
cancer targetability and anticancer efficacy of nanoparticles (NPs). Furthermore,
synergistic effects were observed when using different interventional techniques
together on NPs directed cancer treatments. On the other hand, NPs improved
thermal ablation as well by fundamentally improving heating efficiency,
facilitating heat triggered local drug delivery, and increasing cancer control in
marginal peri-ablated zones and distant regions. CONCLUSION: Crossing
applications of the both techniques such as percutaneous delivery of near
infrared (NIR) into deep tumors by needle insertion and conformal thermal
ablation are highly anticipated.
PMID- 28699510
TI - Cell Penetrating Peptides: A Promising Tool for the Cellular Uptake of
Macromolecular Drugs.
AB - The lipid bilayer of the plasma membrane is a selective impermeable barrier for
the internalization of most macromolecules. Cell penetrating peptides (CPPs)
could cross the plasma membrane barrier to deliver various molecules into cells
and are considered as a promising tool to deliver macromolecular drugs. However,
the exact cellular uptake mechanisms of CPPs are still ambiguous. It was reported
that the exact cellular uptake pathway was determined by numerous factors such as
the amino acid sequences (hydrophobicity and net charge), extracellular CPP
concentration, cargoes' properties, cell type and the temperature. No matter what
kind of mechanisms, the electrostatic interaction between the positive charged
amino acids and the membrane with negatively charged glycosaminoglycans (GAGs),
especially heparan sulphate proteoglycans (HSPGs), was supposed to be the first
crucial step for CPPs uptake. The first recognition triggers cytoskeletal
remodeling via activating Rho/Rac GTPases and kinase C, followed by the cell
surface microdomains changing, ligand binding and cellular uptake. This review
briefly discusses the classification, structure-activity relationships, cellular
uptake mechanisms and biomedical applications of CPPs.
PMID- 28699511
TI - Striatal-enriched Tyrosine Protein Phosphatase (STEP) in the Mechanisms of
Depressive Disorders.
AB - Striatal-enriched tyrosine protein phosphatase (STEP) is expressed mainly in the
brain. Its dysregulation is associated with Alzheimer's and Huntington's
diseases, schizophrenia, fragile X syndrome, drug abuse and stroke/ischemia.
However, an association between STEP and depressive disorders is still obscure.
The review discusses the theoretical foundations and experimental facts
concerning possible relationship between STEP dysregulation and depression risk.
STEP dephosphorylates and inactivates several key neuronal signaling proteins
such as extracellular signal-regulating kinase 1 and 2 (ERK1/2), stress activated
protein kinases p38, the Src family tyrosine kinases Fyn, Pyk2, NMDA and AMPA
glutamate receptors. The inactivation of these proteins decreases the expression
of brain derived neurotrophic factor (BDNF) necessary for neurogenesis and
neuronal survival. The deficit of BDNF results in progressive degeneration of
neurons in the hippocampus and cortex and increases depression risk. At the same
time, a STEP inhibitor, 8-(trifluoromethyl)-1,2,3,4,5-benzopentathiepin-6-amine
hydrochloride (TC-2153), increases BDNF expression in the hippocampus and
attenuated the depressivelike behavior in mice. Thus, STEP is involved in the
mechanism of depressive disorders and it is a promising molecular target for
atypical antidepressant drugs of new generation.
PMID- 28699512
TI - A Review of the Mechanism of Action of Amphibian Antimicrobial Peptides Focusing
on Peptide-Membrane Interaction and Membrane Curvature.
AB - Research interests on amphibian antimicrobial peptides (AMPs) are currently
increasing because of their capability to combat microorganisms from both
terrestrial and aquatic environments, which are the warehouses of human
pathogens. The most remarkable feature of AMPs are their mechanism of action,
primarily targeted to anionic membranes. Researchers have postulated many models
to describe peptide- membrane interaction, which leads to membrane
permeation/intracellular targeting. Despite these models information regarding
the relationship between membrane curvature and peptidemembrane interaction is
scarce. This relationship could be clearly depicted using the two-state model and
interfacial activity model. In the review, we discuss in detail the two state and
interfacial activity models and explain the influence of membrane curvature on
peptide binding and the membrane interaction of curvature-sensitive peptides. In
addition, the models proposed to explain the mechanism of action of membrane
lytic and non-lytic AMPs are also reviewed.
PMID- 28699513
TI - PARP Inhibitor Drugs in the Treatment of Breast, Ovarian, Prostate and Pancreatic
Cancers: An Update of Clinical Trials.
AB - BACKGROUND: PARP inhibitors appear to offer a promising role in the accompaniment
of many of the cytotoxic agents used in the present day to combat cancer
proliferation in BRCA 1/2 deficient tumors. Current species of PARP inhibitors
have yet to demonstrate a superior effect to that of existing therapies when
administered as a single agent; however, they have appeared to amplify the effect
of these existing chemotherapies when utilized together. This suggests that PARP
inhibitors could play an effective maintenance role in current cancer-combating
strategies. In the immediate future, PARP inhibitors may only be applicable to a
select group of cancers (i.e., those caused by defective HR pathways), though
research is emerging that could indicate an extension of applicability to HR
proficient cancer types as well. For the time being, however, the current
literature suggests that a viable PARP inhibitorchemotherapy hybrid targeting HR
deficient cancers could be well on its way very soon. OBJECTIVE: In this
manuscript we explores the ongoing and the completed clinical trials for
different PARP inhibitors. CONCLUSION: Since the approval of Olaparib by both FDA
and EMA, further clinical trials continue to investigate the use of Olaparib and
other PARP inhibitors. The anticipating outcome of these trials may clarify the
benefit of PARP inhibitors in management of various BRCA mutated solid tumors.
PMID- 28699514
TI - Monoterpenes as Perspective to Chronic Pain Management: A Systematic Review.
AB - BACKGROUND: Individuals with chronic diseases have persistent pain as the main
symptom, which can often reduce their life quality and functional capacity. The
suffering of patients results from the interaction of aversive perception of pain
with physical disability, social and family isolation, financial worries and fear
of mutilation and death. As an individual and subjective phenomenon that involves
many complex aspects, chronic pain should be evaluated and treated in its various
components. Several drugs are currently used, but besides the high cost, they
have side effects that are harmful to patients. Therefore, there is the need to
search for new options for pain relief. Natural products as monoterpenes have
been the target of many researchers. OBJECTIVE: This systematic review aimed to
briefly summarize the knowledge of the analgesic potential of monoterpenes facing
chronic pain. RESULTS: After a search in PubMed, Lilacs, Scopus and Cochrane, 27
articles were selected, which described the analgesic potential of 16
monoterpenes for relief of chronic pain. CONCLUSION: After analyzing the data, it
can be suggested that these compounds are strong candidates for the treatment of
painful states.
PMID- 28699515
TI - Cell Wall Associated Factors of Mycobacterium tuberculosis as Major Virulence
Determinants: Current Perspectives in Drugs Discovery and Design.
AB - BACKGROUND: Mycobacteria genus is responsible for deadly diseases like
tuberculosis and leprosy. Cell wall of bacteria belonging to this genus is unique
in many ways. It plays a major role in the pathogenesis and intracellular
survival inside the host. In intracellular pathogens, their cell wall acts as
molecular shield and interacts with host cell milieu to modulate host defense
responses. OBJECTIVES: In this review, we summarize the factors that participate
in the biosynthesis of unique mycobacterial cell wall, understand their potential
as drug targets and the recent developments where they have been evaluated as
possible drug targets. RESULTS: Several cell wall associated factors that play
crucial roles in the synthesis of cell wall components like Antigen 85 complex,
Glycosyltransferases (GTs), LM (lipomannan) and LAM (lipoarabinomannan), mAGP
Complex, lipolytic enzyme have been categorically documented. Most of the
presently used anti TB regimens interrupted cell wall synthesis, but the
emergence of drug resistant strains made it mandatory to identify new drug
targets. Novel drug candidates which could inhibit the synthesis of cell wall
components have been thoroughly studied worldwide. CONCLUSION: Studies
demonstrated that the cell wall components are unique in terms of their
contribution in mycobacterium pathogenesis. Targeting these can hamper the growth
of M. tuberculosis. In this study, we scrutinize the drugs under trials and the
potential candidates screened through in silico findings.
PMID- 28699516
TI - Induction of Synthetic Lethality by Natural Compounds Targeting Cancer Signaling.
AB - Despite the breakthroughs that have been achieved, significant unmet needs
relating to the inadequate efficacy and toxicity of currently-available cancer
therapies remain. Kinase inhibitors are a class of agents that target signaling
factors responsible for the survival of malignant cells, and may address at least
some of these issues. The concept of synthetic lethality provides a potential
solution to counteract pathway redundancies, and refers to situations in which a
mutation in one of two particular genes alone permits cell survival, while
simultaneous mutation in both results in cell death. When exploited in the
context of cancer therapy, pathways that are uniquely upregulated in cancer cells
become selective targets, with reduced off-target toxicity toward their healthy
counterparts. Natural compounds represent a large and readily-accessible library
of bioactive structures that can be screened for synthetically lethal
interactions by testing for the inhibition of kinases relevant to cancer cell
survival. In this review, we discuss the concept of synthetic lethality and focus
on scenarios in which natural compounds that target kinases may be applied to tip
the balance in favor of cancer cell death during therapeutic challenge.
PMID- 28699518
TI - Nano-sized Ultrasound Contrast Agents for Cancer Therapy and Theranostics.
AB - Ultrasound contrast agents (UCA) represented by gas-filled microbubble, can
provide simultaneous and co-localized enhancement on image contrast to help
disease diagnosis by highlighting tissue borders. Nowadays, Some UCAs (e.g.
Levovist(r), Optison(r), Definity(r), and Sonovue(r)) are commercially available,
and have been clinically utilized for enhanced ultrasonography in the US, Canada,
Europe, Asia and so on. However, their large diameters (1~10 um) mainly hinder
more precise and deeper applications in the imaging of capillaryabundant organs
or tissues (e.g. tumor), and undersized nanoscale UCAs also lack enough
backscattering echo intensity to distinguish abnormal distribution of vessels. So
novel shapes, structures and materials of nano-sized UCAs are constantly emerging
for cancer ultrasonic imaging. Particularly, the cavitation effect of diagnostic
ultrasound can accelerate effusion of loaded contents from UCAs, following
cellular uptake. This will inevitably contribute to develop other potential
applications of nano-sized UCAs towards cancer therapy and theranostics.
PMID- 28699517
TI - Circadian MicroRNAs in Cardioprotection.
AB - The most dramatic feature of life on Earth is our adaptation to the cycle of day
and night. Throughout evolutionary time, almost all living organisms developed a
molecular clock linked to the light-dark cycles of the sun. In present time, we
know that this molecular clock is crucial to maintain metabolic and physiological
homeostasis. Indeed, a dysregulated molecular clockwork is a major contributing
factor to many metabolic diseases. In fact, the time of onset of acute myocardial
infarction exhibits a circadian periodicity and recent studies have found that
the light regulated circadian rhythm protein Period 2 (PER2) elicits endogenous
cardioprotection from ischemia. Manipulating the molecular clockwork may prove
beneficial during myocardial ischemia in humans. MicroRNAs are small non-coding
RNA molecules capable of silencing messenger RNA (mRNA) targets. MicroRNA
dysregulation has been linked to cancer development, cardiovascular and
neurological diseases, lipid metabolism, and impaired immunity. Therefore,
microRNAs are gaining interest as putative novel disease biomarkers and
therapeutic targets. To identify circadian microRNA-based cardioprotective
pathways, a recent study evaluated transcriptional changes of PER2 dependent
microRNAs during myocardial ischemia. Out of 352 most abundantly expressed
microRNAs, miR-21 was amongst the top PER2 dependent microRNAs and was shown to
mediate PER2 elicited cardioprotection. Further analysis suggested circadian
entrainment via intense light therapy to be a potential strategy to enhance miR
21 activity in humans. In this review, we will focus on circadian microRNAs in
the context of cardioprotection and will highlight new discoveries, which could
lead to novel therapeutic concepts to treat myocardial ischemia.
PMID- 28699519
TI - The Tat/P-TEFb Protein-Protein Interaction Determining Transcriptional Activation
of HIV.
AB - Human immunodeficiency virus type (HIV) transcription is crucial for its life
cycle and is primarily involved in the maintenance of viral latency. HIV
transcription is regulated by both viral and cellular transcription factors.
Numerous epigenetic factors, as well as transcriptional suppressor proteins, play
major roles in the maintenance of transcriptional silencing of viral gene
expression from the proviral DNA. Once inducible transcription factors such as
nuclear factor kappaB are activated through extracellular signaling, viral
latency is terminated and transcription from the silenced proviral DNA is
initiated. Transcriptional induction by cellular factors is immediately followed
by high gene expression via the function of the virus-encoded transcriptional
activator Tat. Interestingly, unlike other known transcriptional activators, Tat
primarily activates transcriptional elongation, rather than initiation, by
interacting with and activating cellular positive transcriptional elongation
factor b (P-TEFb). In this review, we describe how HIV transcription is
negatively and positively regulated through its life cycle and the molecular
mechanism underlying how Tat activates viral transcription. We propose a novel
strategy against viral replication in which regulated transcriptional processes
play important roles in determining the extent of viral replication. The
structural details of how Tat interacts with P-TEFb are described, which may be
useful for the development of effective and specific anti-HIV therapies.
PMID- 28699520
TI - Therapeutic Strategy of Targeting Astrocytes for Neuroprotection in Parkinson's
Disease.
AB - Parkinson's disease (PD) is one of common neurodegenerative diseases, which shows
motor symptoms including tremor, bradykinesia, rigidity and postural instability.
It also involves non-motor symptoms such as cognitive impairment, mental
manifestation, autonomic disorder and sensory disturbance. Although treatments to
improve the motor disability in PD are being assessed at present, the main
challenge remains that is the development of neuroprotective or disease-modifying
treatments. Therefore, it is desirable to find approaches that can inhibit the
progression of dopaminergic neurodegeneration. Astrocytes are known to play an
important role in the maintenance of the neuronal environment and exert
neuroprotective effects. Additionally, astrocyte dysfunction increases the
susceptibility of neurons to cytotoxicity. We have demonstrated neuroprotective
approaches in parkinsonian models in various studies targeting astrocytes. In
this article, we summarize the neuroprotective function of astrocytes in the
brain, involvement of astrocyte dysfunction in neurodegeneration, and
experimental approaches to dopaminergic neuroprotection. We review findings
reported in several papers including our own studies. We also address target
molecules and pivotal pathways in astrocytes for dopaminergic neuroprotection.
The review discusses new promising therapeutic strategies to prevent dopaminergic
neurodegeneration in PD.
PMID- 28699521
TI - Astrocyte: An Innovative Approach for Alzheimer's Disease Therapy.
AB - Alzheimer's disease (AD) is a devastating neurological illness with a heavy
economic impact. Further comorbidities in combination with the social impact of
this disorder increase the urgency of a clearer comprehension of its
etiopathogenesis, allowing the execution of novel therapeutic strategies. Despite
astrocytes have been widely described as active participant in the regulation of
cerebral circuits, available data are still poor. Even less information is
available about their precise role in the pathogenesis of illness. Moreover, the
scant knowledge about the astrocyte-neuron interplay in health and disease still
impedes pioneering discoveries. The focus of this review is to look for new and
innovative pharmacological approaches against AD. In order to perform this, we
used the following keywords in PubMed search engine: astrocytes, therapy,
Alzheimer's disease, and glia in different combinations. With this review, we
collected data available in literature describing how also astrocytes besides
neurons might be new potential targets for drug discovery. Different approaches
currently being studied include modulation of glutamate transporters expression,
astroglial genetic manipulation, free radicals inhibition, up-regulation of
neurotrophins, and regulation of astrogliosis and neuroinflammation. Since
several studies already demonstrated that astrocytes are definitely involved in
AD pathogenesis, these cells can represent a promising new therapeutic target.
PMID- 28699522
TI - Targeting Human Astrocytes' Calcium-sensing Receptors for Treatment of
Alzheimer's Disease.
AB - Understanding the pathophysiology of Alzheimer's disease (AD) in the principal
human neural cells is necessary for finding therapeutics for this illness. To
help do this, we have been using freshly cultured functionally normal cerebral
cortical adult human astrocytes (NAHAs) and postnatal neurons. The findings show
that amyloid-beta oligomers (Abeta-os) binding to calcium-sensing receptors
(CaSRs) on NAHAs and neuron surfaces trigger signals capable of driving AD
pathogenesis. This Abeta*CaSR signalling shifts the amyloid precursor protein
(APP) from its alpha-secretase shedding producing neurotrophic/neuroprotective
soluble (s)APPalpha to its beta-secretase cleaving engendering AD-driving
Abeta42/Abeta42-os peptides. Abeta*CaSR signalling in NAHAs also drives the
release of toxic hyper-phosphorylated Tau proteins in exosomes, and of nitric
oxide, and VEGF-A. These several harmful agents comprise the neuron-killing
machinery, driving the very slowly spreading AD neurocontagion. VEGF-A over
secretion from Abeta-exposed blood vessel-attached astrocytes induces a
functional magnetic resonance imaging- detectable hippocampal neoangiogenesis
which indicates approaching AD in amnestic minor cognitive impairment (aMCI)
patients. Most important in AD's regard, selective allosteric CaSR antagonists
(calcylitics) added to Abeta42/Abeta42-os-exposed NAHAs (or to human neuron
cultures) rescue the extracellular shedding of neurotrophic/ neuroprotective
sAPPalpha and suppress all the neurotoxic effects of Abeta*CaSR signalling even
when multiple microglial cytokines are also present. Therefore, since the
multipotent calcilytics would be reasonably safe and inexpensive drugs for
humans, it is worthwhile testing them as AD therapeutics in clinical trials
especially in persons in the earliest detectable stages of AD neuropathology
progression such as aMCI.
PMID- 28699523
TI - Altered Homeostatic Functions in Reactive Astrocytes and Their Potential as a
Therapeutic Target After Brain Ischemic Injury.
AB - Brain ischemic injury represents one of the greatest medical challenges for the
aging population in developed countries, yet despite strong efforts,
possibilities to treat ischemic injury still remain poor. Stroke, the most common
type of brain ischemic injury in humans, is caused by brain artery occlusion, and
represents a focal form of ischemia, which leads to neuronal loss in the ischemic
core, and glial scar formation in the penumbral region around the core. Such
glial scar mainly comprises reactive astrocytes, reactive NG2 glia and activated
microglia. Reactive astrocytes display distinct features when compared to healthy
astroglia, including changes in their morphology, metabolism, gene expression
profiles, production of extracellular matrix proteins or proliferation rate.
Similarly to astrocytes in the healthy nervous tissue, reactive astrocytes
surrounding the glial scar strongly influence the activity of surviving neurons
around the ischemic lesion. Bringing insight into pathophysiological functions of
reactive astrocytes within the glial scar might thus open new possibilities for
stroke treatment. Here, we summarize the properties of reactive astrocytes, with
emphasis on the expression and function of ion channels, transporters and
neurotransmitter receptors; all of which possess the ability to change the
functional state of astrocytes, such as the membrane equilibrium potentials for
different ions. This may have major effects on the functioning of surviving
neurons, consequently leading to changes in neuronal excitability and progression
of secondary pathologies, such as epilepsy. Moreover, we provide possible clues
for therapy, based on functional modulation of astrocytic ion transporting
mechanisms.
PMID- 28699524
TI - Biohybrid Membrane Systems for Testing Molecules and Stem Cell Therapy in
Neuronal Tissue Engineering.
AB - Current research in neural tissue-engineering is focused on the development of
advanced biomaterials for the creation of sophisticated neuro-tissue analogues,
showing that mimicking the in vivo tissue disposition and functions is a useful
tool for the study of brain-related issues in normal and pathological states. In
addition, the most common approach for developing new drug therapies is to carry
out in vitro investigation before in vivo test, thus, it is increasingly
important to develop valuable models that can predict the results of in vivo
studies. This review presents the recent state of the art concerning the
multifunctional role of biohybrid membrane systems in neuronal tissue engineering
as innovative in vitro platforms with a well-controlled microenvironment, that
enhance nervous system repair by guiding neuronal growth and differentiation. In
vitro membrane-based models of brain tissue, created by combining neurons,
membranes and therapeutic molecules, were described highlighting the innovative
approaches directed to investigate specific biological phenomena as well as for
testing biopharmaceutical compounds in neurodegenerative diseases, and drug
delivery to the CNS. Furthermore, several examples of in vivo application of
membrane-based stem cell delivery approaches for nerve regeneration were
summarized.
PMID- 28699525
TI - Hybrid Materials and Nanocomposites as Multifunctional Biomaterials.
AB - This review article provides an overview of hybrid and nanocomposite materials
used as biomaterials in nanomedicine, focusing on applications in controlled drug
delivery, tissue engineering, biosensors and theranostic systems. Special
emphasis is placed on the importance of tuning the properties of nanocomposites,
which can be achieved by choosing appropriate synthetic methods and seeking
synergy among different types of materials, particularly exploiting their
nanoscale nature. The challenges in fabrication for the nanocomposites are
highlighted by classifying them as those comprising solely inorganic phases
(inorganic/inorganic hybrids), organic phases (organic/organic hybrids) and both
types of phases (organic/inorganic hybrids). A variety of examples are given for
applications from the recent literature, from which one may infer that
significant developments for effective use of hybrid materials require a delicate
balance among structure, biocompatibility, and stability.
PMID- 28699526
TI - Hydrogel-Based Cell Therapies for Kidney Regeneration: Current Trends in
Biofabrication and In Vivo Repair.
AB - Facing the problems of limited renal regeneration capacity and the persistent
shortage of donor kidneys, dialysis remains the only treatment option for many
end-stage renal disease patients. Unfortunately, dialysis is only a medium-term
solution because large and protein-bound uremic solutes are not efficiently
cleared from the body and lead to disease progression over time. Current
strategies for improved renal replacement therapies (RRTs) range from whole organ
engineering to biofabrication of renal assist devices and biological injectables
for in vivo regeneration. Notably, all approaches coincide with the incorporation
of cellular components and biomimetic micro-environments. Concerning the latter,
hydrogels form promising materials as scaffolds and cell carrier systems due to
the demonstrated biocompatibility of most natural hydrogels, tunable biochemical
and mechanical properties, and various application possibilities. In this review,
the potential of hydrogel-based cell therapies for kidney regeneration is
discussed. First, we provide an overview of current trends in the development of
RRTs and in vivo regeneration options, before examining the possible roles of
hydrogels within these fields. We discuss major application-specific hydrogel
design criteria and, subsequently, assess the potential of emergent
biofabrication technologies, such as micromolding, microfluidics and
electrodeposition for the development of new RRTs and injectable stem cell
therapies.
PMID- 28699527
TI - Bioinformatics Approaches to Profile the Tumor Microenvironment for
Immunotherapeutic Discovery.
AB - In the microenvironment of a malignancy, tumor cells do not exist in isolation,
but rather in a diverse ecosystem consisting not only of heterogeneous tumor-cell
clones, but also normal cell types such as fibroblasts, vasculature, and an
extensive pool of immune cells at numerous possible stages of activation and
differentiation. This results in a complex interplay of diverse cellular
signaling systems, where the immune cell component is now established to
influence cancer progression and therapeutic response. It is experimentally
difficult and laborious to comprehensively and systematically profile these
distinct cell types from heterogeneous tumor samples in order to capitalize on
potential therapeutic and biomarker discoveries. One emerging solution to address
this challenge is to computationally extract cell-type specific information
directly from bulk tumors. Such in silico approaches are advantageous because
they can capture both the cell-type specific profiles and the tissue systems
level of cell-cell interactions. Accurately and comprehensively predicting these
patterns in tumors is an important challenge to overcome, not least given the
success of immunotherapeutic drug treatment of several human cancers. This is
especially challenging for subsets of closely related immune cell phenotypes with
relatively small gene expression differences, which have critical functional
distinctions. Here, we outline the existing and emerging novel bioinformatics
strategies that can be used to profile the tumor immune landscape.
PMID- 28699528
TI - Targeting CD147 is a Novel Strategy for Antitumor Therapy.
AB - CD147 is a membrane protein belonging to immunoglobulin superfamily and expressed
in the cell membrane, which is also named with an extracellular matrix
metalloproteinase inducer (EMMPRIN) because this molecule induces adjacent
fibroblasts or tumor cells to produce MMPs, facilitating tumor cells migration
and invasion. Accumulating evidences have shown that CD147 is over-expressed in
various tumors, including melanoma, liver cancer, and lung cancer, and
orchestrates tumor cell proliferation, apoptosis, invasion and metastasis,
multidrug resistance and glycolysis through critical molecules such as MMPs,
MCTs, Caveolin-1, and VEGF. In this review, we focus on understanding the
characteristics of CD147 in various biological functions, including physiological
and pathological processes. Recent novel studies have shown that CD147 is not
only a potential diagnostic marker but also a therapeutic target for chemotherapy
or the diagnosis of cancer.
PMID- 28699529
TI - Targeting Protein Kinases for the Treatment of Glioblastoma Multiforme: Linking
Basic Studies to Clinical Applications.
AB - Glioblastoma multiforme (GBM) is the most common malignant primary brain tumor in
adults with intensive heterogeneity and one of the most lethal human cancers.
Protein kinases control diverse cellular processes by coordinating different
signaling pathways. Protein kinases are frequently dysregulated in human cancers,
which contributes to tumor initiation and development. Thus, protein kinases are
a growing drug target class for cancers including glioblastoma. This review
focuses on the most important protein kinases and kinase-mediated signaling
cascades in glioblastoma, and discusses the functional mechanism of these kinases
in glioblastoma tumorigenesis. Moreover, this review has summarized the most
recent preclinical and clinical advances of agents targeting protein kinases in
the treatment of glioblastoma.
PMID- 28699530
TI - Gene Delivery with Organic Electronic Biomaterials.
AB - Gene therapy may be capable of treating a variety of diseases, a prerequisite of
which is the successful delivery of polynucleic acids (e.g., DNA, RNA) to a
patient's cells. Delivery can be achieved technologically (e.g., using
electroporation), using viruses (natural gene delivery vectors) or non-viral
vectors (e.g., lipids, nanoparticles, polymers). This article aims to give the
reader an overview of the use of organic electronic materials (i.e., fullerenes,
graphenes and conjugated polymers) as non-viral gene delivery vectors.
PMID- 28699531
TI - Identification of Antineoplastic Targets with Systems Approaches, Using
Resveratrol as an In-Depth Case Study.
AB - The identification and validation of novel drug-target combinations are key steps
in the drug discovery processes. Cancer is a complex disease that involves
several genetic and environmental factors. High-throughput omics technologies are
now widely available, however the integration of multi-omics data to identify
viable anticancer drug-target combinations, that allow for a better clinical
outcome when considering the efficacy-toxicity spectrum, is challenging. This
review article provides an overview of systems approaches which help to integrate
a broad spectrum of technologies and data. We focus on network approaches and
investigate anticancer mechanism and biological targets of resveratrol using
reverse pharmacophore mapping as an in-depth case study. The results of this case
study demonstrate the use of systems approaches for a better understanding of the
behavior of small molecule inhibitors in receptor binding sites. The presented
network analysis approach helps in formulating hypotheses and provides
mechanistic insights of resveratrol in neoplastic transformations.
PMID- 28699532
TI - Modulation of Heart Rate by Acute or Chronic Aerobic Exercise. Potential Effects
on Blood Pressure Control.
AB - It was initially assumed that heart rate and arterial blood pressure were
modulated by normal respiration and muscle contraction. The arterial baroreflex,
an inverse relationship between blood pressure and heart rate, was later
reported. Nonetheless, it was then assumed that those responses involved vagal
modulation. We summarize available evidence on the modulation of heart rate by
acute or chronic aerobic exercise as well as its potential implications on blood
pressure (BP) control. Numerous studies have tried to clarify whether aerobic
exercise modifies neurally-mediated vasoconstriction, but they report
contradictory results. In view of these incongruities, the aim of this narrative
review is to summarize available evidence on the modulation of heart rate by
acute or chronic aerobic exercise as well as its potential implications on BP
control. We mainly focus on the effects of aerobic exercise in both heart rate
and blood pressure. Heart rate and heart rate variability have been indistinctly
considered similar metrics, but they have completely different meanings when
properly used. Both are risk markers in cardiac disease, whereas heart rate
variability is also an index of sympathovagal modulation of heart rate. On the
other hand, heart rate recovery has been also used as an index for mirroring both
cardiovascular fitness and autonomic function, and can be used as a measure of
vagal reactivation. Importantly, it is now wellknown that a reduced rate of heart
rate recovery represents a powerful predictor of overall mortality. In this
review, due to its complexity, we have included studies in which any of these
three parameters have been analyzed.
PMID- 28699533
TI - Class A GPCRs: Structure, Function, Modeling and Structure-based Ligand Design.
AB - G protein-coupled receptors (GPCRs), especially the class A, are the most heavily
investigated drug targets in the pharmaceutical industry. Tremendous efforts have
been made by both industry and academia to understand the molecular structure and
function of this large family of transmembrane proteins. Our understanding in
GPCR activation has evolved from the classical inactive-active two-state model to
a complex view of GPCR conformational ensemble associated with multiple
interacting partners such as ligands, allosteric modulators, ions and downstream
signaling proteins. New drug targets and ligand design strategies are unveiled.
Meanwhile, breakthroughs in X-ray crystallography have resulted in high
resolution structures of over 30 GPCRs, providing structural basis for drug
design and functional studies. These enabled wide applications of computational
approaches in GPCR research that have led to several groundbreaking studies in
the last few years. While a large fraction of human GPCRs has yet to be
crystallized, homology modeling plays a pivotal role in the simulation of these
GPCRs. Here, we review the recent updates on class A GPCR structure and function,
with a focus on the applications and perspectives of molecular modeling in GPCR
ligand design.
PMID- 28699534
TI - Discovery and Development of ATP-Competitive mTOR Inhibitors Using Computational
Approaches.
AB - The mammalian target of rapamycin (mTOR) is a central controller of cell growth,
proliferation, metabolism, and angiogenesis. This protein is an attractive target
for new anticancer drug development. Significant progress has been made in hit
discovery, lead optimization, drug candidate development and determination of the
three-dimensional (3D) structure of mTOR. Computational methods have been applied
to accelerate the discovery and development of mTOR inhibitors helping to model
the structure of mTOR, screen compound databases, uncover structure-activity
relationship (SAR) and optimize the hits, mine the privileged fragments and
design focused libraries. Besides, computational approaches were also applied to
study protein-ligand interactions mechanisms and in natural product-driven drug
discovery. Herein, we survey the most recent progress on the application of
computational approaches to advance the discovery and development of compounds
targeting mTOR. Future directions in the discovery of new mTOR inhibitors using
computational methods are also discussed.
PMID- 28699535
TI - Protein Kinases as Targets for Opisthorchis viverrini- Associated
Cholangiocarcinoma Therapy.
AB - Protein kinases are enzymes that catalyze the transfer of phosphate from ATP to
the serine/threonine or tyrosine residues of target molecules. These are key
important mediators in a signaling cascade involved in several biological
processes. Dysregulation of their activity has been found in various tumors. From
the increased understanding of kinase structure and activation mechanisms emerged
new strategies for targeting kinase in cancer treatment. Nowadays, kinase
specific inhibitors are developed and widely used for clinical cancer treatment.
In this review, we focus on protein kinases that are involved in
cholangiocarcinoma (CCA). CCA is a slow progression tumor that is recognized as a
major public health issue in northeastern Thailand. The standard regimen for CCA
treatment is surgical resection. However, the patient's clinical outcome is still
problematic. Therefore, the search to identify molecular mechanisms and molecules
that are involved in carcinogenesis and the progression of CCA that can be used
as therapeutic targets is urgently required. Aberrant expression and activation,
as well as the functions of protein kinases in CCA, have been extensively studied
in order to apply them as therapeutic targets. This review provides the
information on protein kinases and their activity in CCA, as well as the
preclinical data on kinase inhibitors that have been evaluated for this cancer.
PMID- 28699536
TI - Supramolecular Self-Assembled Nanogels a New Platform for Anticancer Drug
Delivery.
AB - Polymer micellar nanogels are a group of core-shell polymeric micelles with
swelling properties in aqueous media. Nanogel systems have proven their potential
in controlled, sustained and targetable drug delivery area with no immunological
responses. This review includes a comprehensive wide range of self-assembly of
polymeric nanogels as delivery systems for anticancer drugs. Nanogels are
nanoparticulate drug delivery systems which are specially designed for enhanced
target oriented and cellular uptake of drugs with emphasis on chemotherapeutic
agents studied in this review. Self-assembling nanogels are based on natural
substances or synthetic polymers including: hyaluronic acid, heparin, alginate,
cyclodextrins, chondroeitin sulfate, starch, mannan, chitosan, pullulan, poly(N
isopropylacrylamide), polyvynil alcohol, Pluronic F127, polyacrylic acid,
poly(hydroxylethyl methacrylate), poly[2- (dimethylamino)ethyl methacrylate and
polylactide-co-glycolide-polyethylen glycol amphiphilic di or tri block copolymer
used to deliver anticancer drugs are introduced and discussed.
PMID- 28699537
TI - Recent Advances in Polymeric Nanosystems for Treating Cutaneous Melanoma and Its
Metastasis.
AB - Melanoma shows a high possibility of mortality after it metastasizes because of
its aggressive nature. Although there are several options for anti-melanoma
therapy, this skin malignancy is resistant to some therapies. Chemotherapy,
biochemotherapy, immunotherapy, and adoptive cell therapy have failed to exhibit
a significant amelioration in overall survival. Nanomedicine provides an
opportunity to improve the efficiency of the antimelanoma regimen. Nanoparticles
for treating melanoma provide the advantages over conventional therapies such as
drug solubility increment, drug stability enhancement, epithelium permeability
and bioavailability amelioration, half-life prolonging, tumor targeting, and side
effect minimization. Polymeric nanocarriers are the most extensively studied
platforms for the treatment of a variety of cancers. The polymers' sophisticated
material engineering tailors the controllable physicochemical properties of the
nanoparticles for melanoma penetration via passive and active delivery. The
present study highlights the recent progress on the development of polymeric
nanoparticles for melanoma treatment. We describe the concepts and improvement
mechanisms of the nanomedical techniques for melanoma treatment. Passive
targeting by modifying the structure and physicochemical characters of polymeric
nanocarriers is a strategy for efficient drug delivery to the melanoma and its
metastasis. On the other hand, active targeting such as peptide or antibody
conjugation is another approach delivering the drugs or genes to the nidus site
by the nanocarriers. This review offers an overview of the benefits of polymeric
nanosystems for treating melanoma.
PMID- 28699538
TI - Virtual Screening and Statistical Analysis in the Design of New Caffeine
Analogues Molecules with Potential Epithelial Anticancer Activity.
AB - About 132 thousand cases of melanoma (more severe type of skin cancer) were
registered in 2014 according to the World Health Organization. This type of
cancer significantly affects the quality of life of individuals. Caffeine has
shown potential inhibitory effect against epithelial cancer. In this study, it
was proposed to obtain new caffeine-based molecules with potential epithelial
anticancer activity. For this, a training set of 21 molecules was used for
pharmacophore perception procedures. Multiple linear regression analyses were
used to propose mono-, bi-, tri-, and tetra-parametric models applied in the
prediction of the activity. The generated pharmacophore was used to select 350
molecules available at the ZINCpharmer server, followed by reduction to 24
molecules, after selection using the Tanimoto index, yielding 10 molecules after
final selection by predicted activity values > 1.5229. These ten molecules had
better pharmacokinetic properties than the other ones used as reference and
within the clinically significant limits. Only two molecules show minor hits of
toxicity and were submitted to molecular docking procedures, showing BFE (binding
free energy) values lower than the reference values. Statistical analyses
indicated strong negative correlations between BFE and pharmacophoric properties
(high influence on BFE lowering) and practically null correlation between BFE and
BBB. The two most promising molecules can be indicated as candidates for further
in vitro and in vivo analyzes.
PMID- 28699539
TI - Recent Advances in the Function of the 67 kDa Laminin Receptor and its Targeting
for Personalized Therapy in Cancer.
AB - The 67 kDa high affinity laminin receptor (67LR) is a non-integrin cell surface
receptor for laminin, the major component of basement membranes. Interactions
between 67LR and laminin play a major role in mediating cell adhesion, migration,
proliferation and survival. 67LR derives from homo- or hetero-dimerization of a
37 kDa cytosolic precursor (37LRP), most probably by fatty acid acylation.
Interestingly, 37LRP, also called p40 or OFA/iLR (oncofetal antigen/immature
laminin receptor), is a multifunctional protein with a dual activity in the
cytoplasm and in the nucleus. In the cytoplasm, 37LRP it is associated with the
40S subunit of ribosome, playing a critical role in protein translation and
ribosome biogenesis while in the nucleus it is tightly associated with nuclear
structures, and bound to components of the cytoskeleton, such as tubulin and
actin. 67LR is mainly localized in the cell membrane, concentrated in lipid
rafts. Acting as a receptor for laminin is not the only function of 67LR; indeed,
it also acts as a receptor for viruses, bacteria and prions. 67LR expression is
increased in neoplastic cells and correlates with an enhanced invasive and
metastatic potential. The primary function of 67LR in cancer is to promote tumor
cell adhesion to basement membranes, the first step in the invasion-metastasis
cascade. Thus, 67LR is overexpressed in neoplastic cells as compared to their
normal counterparts and its overexpression is considered a molecular marker of
metastatic aggressiveness in cancer of many tissues, including breast, lung,
ovary, prostate, stomach, thyroid and also in leukemia and lymphoma. Thus,
inhibiting 67LR binding to laminin could be a feasible approach to block cancer
progression. Here, we review the current understanding of the structure and
function of this molecule, highlighting its role in cancer invasion and
metastasis and reviewing the various therapeutic options targeting this receptor
that could have a promising future application.
PMID- 28699540
TI - DNA Base Excision Repair: The Achilles' Heel of Tumour Cells and their
Microenvironment?
AB - Our current understanding of cancer suggests that every tumour has individual
features. Approaches to cancer treatment require thorough comprehension of the
mechanisms triggering genomic instability and protecting cancer cells from
therapeutic treatments. Base excision repair (BER) is a frontline DNA repair
system that is responsible for maintaining genome integrity. The BER pathway
prevents the occurrence of disease, including cancer, by constantly repairing DNA
base lesions and DNA single strand breaks caused by endogenous and exogenous
mutagens. BER is an important DNA repair system for cancer cell survival, as it
can affect both chemoand radio-resistance of tumours. Variations in BER capacity
are likely responsible for a number of cases of sporadic cancer and may also
modulate cancer sensitivity and resistance to therapeutic treatments. For these
reasons, it is broadly accepted that targeting BER enzymes might be a promising
approach to personalised anti-cancer therapy. However, recent advances in both
treatment strategies and the comprehension of cancer development call for a
better understanding of the consequences of BER inhibition. Indeed, the impact on
both the tumour microenvironment and healthy tissues is still unclear. This
review will summarise the current status of the approaches exploiting BER
targeting, describing the most promising small molecule inhibitors and synthetic
lethality strategies, as well as potential limitations of these approaches.
PMID- 28699541
TI - Randomised controlled trials and changing public health practice.
AB - One reason for doing randomised controlled trials (RCTs) is that experiments can
be convincing. Early epidemiological experimenters, such as Jenner and the
smallpox vaccine and Snow and his famous Broad Street pump handle, already knew
the answer they were demonstrating; they used the experiments as knowledge
translation devices to convince others.More sophisticated modern experiments
include cluster randomised controlled trials (CRCTs) for experiments in the
public health setting. The knowledge translation value remains: RCTs and CRCTs
can potentially stimulate changes of practice among stakeholders. Capitalising on
the knowledge translation value of RCTs requires more than the standard reporting
of trials. Those who are convinced by a trial and want to act, need to know how
the trial relates to their own context, what contributed to success, and what
might make it even more effective. Implementation research unpacks the back
story, examining how and why an intervention worked.The Camino Verde trial of
community mobilisation for control of dengue reported a significant impact on
entomological indices of the Aedes aegypti vector, and on serological dengue
virus infection and self-reported dengue cases. This important study should lead
to studies of similar interventions in other contexts, and ultimately to changes
in dengue control practices. This supplement is the back-story of the trial,
providing information to help researchers and planners to make use of the trial
findings.Background articles include the full protocol, a systematic review of
CRCTs of approaches for Aedes aegypti control, epidemiological and entomological
findings from the baseline survey, and how baseline findings were used to set up
the intervention. Secondary analyses of the entomological findings examine
associations with the use of the larvicide temephos, and the impact of the
intervention in different conditions of water supply and seasons.Other articles
describe implementation and other impacts: the underlying approach;
implementation in the trial's different social contexts; the different impact in
women and men; the effects of using fish for vector control; the impact on
household costs of personal protection and of cases of dengue illness; and
ethical issues.We hope this supplement will increase the knowledge translation
value of the Camino Verde trial.
PMID- 28699542
TI - Community cost-benefit discussions that launched the Camino Verde intervention in
Nicaragua.
AB - BACKGROUND: Recent literature on community intervention research stresses system
change as a condition for durable impact. This involves highly participatory
social processes leading to behavioural change. METHODS: Before launching the
intervention in the Nicaraguan arm of Camino Verde, a cluster-randomised
controlled trial to show that pesticide-free community mobilisation adds
effectiveness to conventional dengue controls, we held structured discussions
with leaders of intervention communities on costs of dengue illness and dengue
control measures taken by both government and households. These discussions were
the first step in an effort at Socialising Evidence for Participatory Action
(SEPA), a community mobilisation method used successfully in other contexts.
Theoretical grounding came from community psychology and behavioural economics.
RESULTS: The leaders expressed surprise at how large and unexpected an economic
burden dengue places on households. They also acknowledged that large investments
of household and government resources to combat dengue have not had the expected
results. Many were not ready to see community preventive measures as a substitute
for chemical controls but all the leaders approved the formation of "brigades" to
promote chemical-free household control efforts in their own communities.
CONCLUSIONS: Discussions centred on household budget decisions provide a good
entry point for researchers to engage with communities, especially when the
evidence showed that current expenditures were providing a poor return. People
became motivated not only to search for ways to reduce their costs but also to
question the current response to the problem in question. This in turn helped
create conditions favourable to community mobilisation for change. TRIAL
REGISTRATION: ISRCTN27581154 .
PMID- 28699543
TI - A signal detection method for temporal variation of adverse effect with vaccine
adverse event reporting system data.
AB - BACKGROUND: To identify safety signals by manual review of individual report in
large surveillance databases is time consuming; such an approach is very unlikely
to reveal complex relationships between medications and adverse events. Since the
late 1990s, efforts have been made to develop data mining tools to systematically
and automatically search for safety signals in surveillance databases. Influenza
vaccines present special challenges to safety surveillance because the vaccine
changes every year in response to the influenza strains predicted to be prevalent
that year. Therefore, it may be expected that reporting rates of adverse events
following flu vaccines (number of reports for a specific vaccine-event
combination/number of reports for all vaccine-event combinations) may vary
substantially across reporting years. Current surveillance methods seldom
consider these variations in signal detection, and reports from different years
are typically collapsed together to conduct safety analyses. However, merging
reports from different years ignores the potential heterogeneity of reporting
rates across years and may miss important safety signals. METHOD: Reports of
adverse events between years 1990 to 2013 were extracted from the Vaccine Adverse
Event Reporting System (VAERS) database and formatted into a three-dimensional
data array with types of vaccine, groups of adverse events and reporting time as
the three dimensions. We propose a random effects model to test the heterogeneity
of reporting rates for a given vaccine-event combination across reporting years.
The proposed method provides a rigorous statistical procedure to detect
differences of reporting rates among years. We also introduce a new visualization
tool to summarize the result of the proposed method when applied to multiple
vaccine-adverse event combinations. RESULT: We applied the proposed method to
detect safety signals of FLU3, an influenza vaccine containing three flu strains,
in the VAERS database. We showed that it had high statistical power to detect the
variation in reporting rates across years. The identified vaccine-event
combinations with significant different reporting rates over years suggested
potential safety issues due to changes in vaccines which require further
investigation. CONCLUSION: We developed a statistical model to detect safety
signals arising from heterogeneity of reporting rates of a given vaccine-event
combinations across reporting years. This method detects variation in reporting
rates over years with high power. The temporal trend of reporting rate across
years may reveal the impact of vaccine update on occurrence of adverse events and
provide evidence for further investigations.
PMID- 28699544
TI - Informed community mobilization for dengue prevention in households with and
without a regular water supply: Secondary analysis from the Camino Verde trial in
Nicaragua.
AB - BACKGROUND: Studies in different countries have identified irregular water supply
as a risk factor for dengue virus transmission. In 2013, Camino Verde, a cluster
randomised controlled trial in Managua, Nicaragua, and Mexico's Guerrero State,
demonstrated impact of evidence-based community mobilisation on recent dengue
infection and entomological indexes of infestation by Aedes aegypti mosquitoes.
This secondary analysis of data from the trial impact survey asks: (1) what is
the importance of regular water supply in neighbourhoods with and without the
trial intervention and (2) can community interventions like Camino Verde
reasonably exclude households with adequate water supply? METHODS: Entomological
data collected in the dry season of 2013 in intervention and control communities
allow contrasts between households with regular and irregular water supplies.
Indicators of entomological risk included the House Index and pupa positive
household index. Generalised linear mixed models with cluster as a random effect
compared households with and without regular water, and households in
intervention and control communities. RESULTS: For the House Index, regular water
supply was associated with a protection in both intervention households (OR 0.7,
95%CI 0.6-0.9) and control households (OR 0.6, 95%CI 0.5-0.8). For the pupa
positive household index, we found a similar protection from regular water supply
in intervention households (OR 0.6, 95%CI 0.4-0.8) and control households (OR
0.7, 95%CI 0.5-0.9). The Camino Verde intervention had a similar impact on House
Index in households with regular water supply (OR 0.7, 95%CI 0.5-1.0) and
irregular water supply (OR 0.6, 95%CI 0.4-0.8); for the pupa positive household
index, the effect of the intervention was very similar in households with regular
(OR0.5, 95%CI 0.3-0.8) and irregular (OR 0.5, 95%CI 0.3-0.9) water supply.
CONCLUSION: While Aedes aegypti control efforts based on informed community
mobilisation had a strong impact on households without a regular water supply,
this intervention also impacted entomological indices in households with a
regular water supply. These households should not be excluded from community
mobilisation efforts to reduce the Aedes aegypti vector. TRIAL REGISTRATION:
ISRCTN27581154 .
PMID- 28699545
TI - Predictive models for pressure ulcers from intensive care unit electronic health
records using Bayesian networks.
AB - BACKGROUND: We develop predictive models enabling clinicians to better understand
and explore patient clinical data along with risk factors for pressure ulcers in
intensive care unit patients from electronic health record data. Identifying
accurate risk factors of pressure ulcers is essential to determining appropriate
prevention strategies; in this work we examine medication, diagnosis, and
traditional Braden pressure ulcer assessment scale measurements as patient
features. In order to predict pressure ulcer incidence and better understand the
structure of related risk factors, we construct Bayesian networks from patient
features. Bayesian network nodes (features) and edges (conditional dependencies)
are simplified with statistical network techniques. Upon reviewing a network
visualization of our model, our clinician collaborators were able to identify
strong relationships between risk factors widely recognized as associated with
pressure ulcers. METHODS: We present a three-stage framework for predictive
analysis of patient clinical data: 1) Developing electronic health record feature
extraction functions with assistance of clinicians, 2) simplifying features, and
3) building Bayesian network predictive models. We evaluate all combinations of
Bayesian network models from different search algorithms, scoring functions,
prior structure initializations, and sets of features. RESULTS: From the EHRs of
7,717 ICU patients, we construct Bayesian network predictive models from 86
medication, diagnosis, and Braden scale features. Our model not only identifies
known and suspected high PU risk factors, but also substantially increases
sensitivity of the prediction - nearly three times higher comparing to logistical
regression models - without sacrificing the overall accuracy. We visualize a
representative model with which our clinician collaborators identify strong
relationships between risk factors widely recognized as associated with pressure
ulcers. CONCLUSIONS: Given the strong adverse effect of pressure ulcers on
patients and the high cost for treating pressure ulcers, our Bayesian network
based model provides a novel framework for significantly improving the
sensitivity of the prediction model. Thus, when the model is deployed in a
clinical setting, the caregivers can suitably respond to conditions likely
associated with pressure ulcer incidence.
PMID- 28699546
TI - An active learning-enabled annotation system for clinical named entity
recognition.
AB - BACKGROUND: Active learning (AL) has shown the promising potential to minimize
the annotation cost while maximizing the performance in building statistical
natural language processing (NLP) models. However, very few studies have
investigated AL in a real-life setting in medical domain. METHODS: In this study,
we developed the first AL-enabled annotation system for clinical named entity
recognition (NER) with a novel AL algorithm. Besides the simulation study to
evaluate the novel AL algorithm, we further conducted user studies with two
nurses using this system to assess the performance of AL in real world annotation
processes for building clinical NER models. RESULTS: The simulation results show
that the novel AL algorithm outperformed traditional AL algorithm and random
sampling. However, the user study tells a different story that AL methods did not
always perform better than random sampling for different users. CONCLUSIONS: We
found that the increased information content of actively selected sentences is
strongly offset by the increased time required to annotate them. Moreover, the
annotation time was not considered in the querying algorithms. Our future work
includes developing better AL algorithms with the estimation of annotation time
and evaluating the system with larger number of users.
PMID- 28699547
TI - Lightweight predicate extraction for patient-level cancer information and
ontology development.
AB - BACKGROUND: Knowledge engineering for ontological knowledgebases is resource and
time intensive. To alleviate these issues, especially for novices, automated
tools from the natural language domain can assist in the development process of
ontologies. We focus towards the development of ontologies for the public health
domain and use patient-centric sources from MedlinePlus related to HPV-causing
cancers. METHODS: This paper demonstrates the use of a lightweight open
information extraction (OIE) tool to derive accurate knowledge triples that can
lead to the seeding of an ontological knowledgebase. We developed a custom
application, which interfaced with an information extraction software library, to
help facilitate the tasks towards producing knowledge triples from textual
sources. RESULTS: The results of our efforts generated accurate extractions
ranging from 80-89% precision. These triples can later be transformed to OWL/RDF
representation for our planned ontological knowledgebase. CONCLUSIONS: OIE
delivers an effective and accessible method towards the development ontologies.
PMID- 28699548
TI - When communities are really in control: ethical issues surrounding community
mobilisation for dengue prevention in Mexico and Nicaragua.
AB - : We discuss two ethical issues raised by Camino Verde, a 2011-2012 cluster
randomised controlled trial in Mexico and Nicaragua, that reduced dengue risk
though community mobilisation. The issues arise from the approach adopted by the
intervention, one called Socialisation of Evidence for Participatory Action.
Community volunteer teams informed householders of evidence about dengue, its
costs and the life-cycle of Aedes aegypti mosquitoes, while showing them the
mosquito larvae in their own water receptacles, without prescribing solutions.
Each community responded in an informed manner but on its own terms. The approach
involves partnerships with communities, presenting evidence in a way that brings
conflicting views and interests to the surface and encourages communities
themselves to deal with the resulting tensions.One such tension is that between
individual and community rights. This tension can be resolved creatively in
concrete day-to-day circumstances provided those seeking to persuade their
neighbours to join in efforts to benefit community health do so in an atmosphere
of dialogue and with respect for personal autonomy.A second tension arises
between researchers' responsibilities for ethical conduct of research and
community autonomy in the conduct of an intervention. An ethic of respect for
individual and community autonomy must infuse community intervention research
from its inception, because as researchers succeed in fostering community self
determination their direct influence in ethical matters diminishes. TRIAL
REGISTRATION: ISRCTN 27581154.
PMID- 28699549
TI - How the public uses social media wechat to obtain health information in china: a
survey study.
AB - BACKGROUND: On average, 570 million users, 93% in China's first-tier cities, log
on to WeChat every day. WeChat has become the most widely and frequently used
social media in China, and has been profoundly integrated into the daily life of
many Chinese people. A variety of health-related information may be found on
WeChat. The objective of this study is to understand how the general public views
the impact of the rapidly emerging social media on health information
acquisition. METHODS: A self-administered questionnaire was designed,
distributed, collected, and analyzed utilizing the online survey tool Sojump.
WeChat was adopted to randomly release the questionnaires using convenience
sampling and collect the results after a certain amount of time. RESULTS: (1) A
total of 1636 questionnaires (WeChat customers) were collected from 32 provinces.
(2) The primary means by which respondents received health education was via the
Internet (71.79%). Baidu and WeChat were the top 2 search tools utilized (90.71%
and 28.30%, respectively). Only 12.41% of respondents were satisfied with their
online health information search. (3) Almost all had seen (98.35%) or read
(97.68%) health information; however, only 14.43% believed that WeChat health
information could improve health. Nearly one-third frequently received and read
health information through WeChat. WeChat was selected (63.26%) as the most
expected means for obtaining health information. (4) The major concerns regarding
health information through WeChat included the following: excessively homogeneous
information, the lack of a guarantee of professionalism, and the presence of
advertisements. (5) Finally, the general public was most interested in
individualized and interactive health information by managing clinicians, they
will highly benefit from using social media rather than Internet search tools.
CONCLUSIONS: The current state of health acquisition proves worrisome. The public
has a high chance to access health information via WeChat. The growing popularity
of interactive social platforms (e.g. WeChat) presents a variety of challenges
and opportunities with respect to public health acquisition.
PMID- 28699550
TI - Household costs for personal protection against mosquitoes: secondary outcomes
from a randomised controlled trial of dengue prevention in Guerrero state,
Mexico.
AB - BACKGROUND: Dengue is a serious public health issue that affects households in
endemic areas in terms of health and also economically, imposing costs for
prevention and treatment of cases. The Camino Verde cluster-randomised controlled
trial in Mexico and Nicaragua assessed the impact of evidence-based community
engagement in dengue prevention. The Mexican arm of the trial was conducted in 90
randomly selected communities in three coastal regions of Guerrero State. This
study reports an analysis of a secondary outcome of the trial: household use of
and expenditure on anti-mosquito products. We examined whether the education and
mobilisation activities of the trial motivated people to spend less on anti
mosquito products. METHODS: We carried out a household questionnaire survey in
the trial communities in 2010 (12,312 households) and 2012 (5349 households in
intervention clusters, 5142 households in control clusters), including questions
about socio-economic status, self-reported dengue illness, and purchase of and
expenditure on insecticide anti-mosquito products in the previous month. We
examined expenditures on anti-mosquito products at baseline in relation to social
vulnerability and we compared use of and expenditures on these products between
intervention and control clusters in 2012. RESULTS: In 2010, 44.2% of 12,312
households reported using anti-mosquito products, with a mean expenditure of
USD4.61 per month among those who used them. Socially vulnerable households spent
less on the products. In 2012, after the intervention, the proportion of
households who purchased anti-mosquito products in the last month was
significantly lower in intervention clusters (47.8%; 2503/5293) than in control
clusters (53.3%; 2707/5079) (difference - 0.05, 95% CIca -0.100 to -0.010). The
mean expenditure on the products, among those households who bought them, was
USD6.43; 30.4% in the intervention clusters and 36.7% in the control clusters
spent more than this (difference - 0.06, 95% CIca -0.12 to -0.01). These
expenditures on anti-mosquito products represent 3.3% and 3.8% respectively of
monthly household income for the poorest 10% of the population in 2012.
CONCLUSIONS: The Camino Verde community mobilisation intervention, as well as
being effective in reducing dengue infections, was effective in reducing
household use of and expenditure on insecticide anti-mosquito products. TRIAL
REGISTRATION: ( ISRCTN27581154 ).
PMID- 28699551
TI - The Camino Verde intervention in Nicaragua, 2004-2012.
AB - : Camino Verde (the Green Way) is an evidence-based community mobilisation tool
for prevention of dengue and other mosquito-borne viral diseases. Its
effectiveness was demonstrated in a cluster-randomised controlled trial conducted
in 2010-2013 in Nicaragua and Mexico. The Nicaraguan arm of the trial was
preceded, from 2004 to 2008, by a feasibility study that provided valuable
lessons and trained facilitators for the trial itself. Here, guided by the
Template for Intervention Description and Replication (TIDieR), we describe the
Camino Verde intervention in Nicaragua, presenting its rationale, its time and
location, activities, materials used, the main actors, modes of delivery, how it
was tailored to encourage community engagement, modifications made from the
feasibility study to the trial itself, and how fidelity to the process originally
designed was maintained. We also present information on costs and discuss the
place of this study within the literature on implementation science. TRIAL
REGISTRATION: ISRCTN27581154 .
PMID- 28699552
TI - Assessing the effects of interventions for Aedes aegypti control: systematic
review and meta-analysis of cluster randomised controlled trials.
AB - BACKGROUND: The Aedes aegypti mosquito is the vector for dengue fever, yellow
fever, chikungunya, and zika viruses. Inadequate vector control has contributed
to persistence and increase of these diseases. This review assesses the evidence
of effectiveness of different control measures in reducing Aedes aegypti
proliferation, using standard entomological indices. METHODS: A systematic search
of Medline, Ovid, BVS, LILACS, ARTEMISA, IMBIOMED and MEDIGRAPHIC databases
identified cluster randomised controlled trials (CRCTs) of interventions to
control Aedes aegypti published between January 2003 and October 2016. Eligible
studies were CRCTs of chemical or biological control measures, or community
mobilization, with entomological indices as an endpoint. A meta-analysis of
eligible studies, using a random effects model, assessed the impact on household
index (HI), container index (CI), and Breteau index (BI). RESULTS: From 848
papers identified by the search, eighteen met the inclusion criteria: eight for
chemical control, one for biological control and nine for community mobilisation.
Seven of the nine CRCTs of community mobilisation reported significantly lower
entomological indices in intervention than control clusters; findings from the
eight CRCTs of chemical control were more mixed. The CRCT of biological control
reported a significant impact on the pupae per person index only. Ten papers
provided enough detail for meta-analysis. Community mobilisation (four studies)
was consistently effective, with an overall intervention effectiveness estimate
of -0.10 (95%CI -0.20 - 0.00) for HI, -0.03 (95%CI -0.05 - -0.01) for CI, and
0.13 (95%CI -0.22 - -0.05) for BI. The single CRCT of biological control had
effectiveness of -0.02 (95%CI -0.07- 0.03) for HI, -0.02 (95%CI -0.04- -0.01) for
CI and -0.08 (95%CI -0.15- -0.01) for BI. The five studies of chemical control
did not show a significant impact on indices: the overall effectiveness was -0.01
(95%CI -0.05- 0.03) for HI, 0.01 (95% CI -0.01- 0.02) for CI, and 0.01 (95%CI
0.03 - 0.05) for BI. CONCLUSION: Governments that rely on chemical control of
Aedes aegypti should consider adding community mobilization to their prevention
efforts. More well-conducted CRCTs of complex interventions, including those with
biological control, are needed to provide evidence of real life impact. Trials of
all interventions should measure impact on dengue risk.
PMID- 28699553
TI - Introduction: the International Conference on Intelligent Biology and Medicine
(ICIBM) 2016: special focus on medical informatics and big data.
AB - In this editorial, we first summarize the 2016 International Conference on
Intelligent Biology and Medicine (ICIBM 2016) held on December 8-10, 2016 in
Houston, Texas, USA, and then briefly introduce the ten research articles
included in this supplement issue. At ICIBM 2016, a special theme, "Medical
Informatics and Big Data," was dedicated to the recent advances of data science
in the medical domain. After peer review, ten articles were selected for this
special issue, covering topics such as Knowledge and Data Personalization, Social
Media Applications to Healthcare, Clinical Natural Language Processing, Patient
Safety Analyses, and Data Mining Using Electronic Health Records.
PMID- 28699554
TI - Coverage and beliefs about temephos application for control of dengue vectors and
impact of a community-based prevention intervention: secondary analysis from the
Camino Verde trial in Mexico.
AB - BACKGROUND: Temephos in domestic water containers remains a mainstay of Latin
American government programmes for control of Aedes aegypti and associated
illnesses, including dengue. There is little published evidence about coverage of
routine temephos programmes. A cluster randomised controlled trial of community
mobilisation in Mexico and Nicaragua reduced vector indices, dengue infection,
and clinical dengue cases. Secondary analysis from the Mexican arm of the trial
examined temephos coverage and beliefs, and the impact of the trial on these
outcomes. METHODS: The trial impact survey in December 2012, in 10,491 households
in 45 intervention and 45 control clusters, asked about visits from the temephos
programme, retention of applied temephos, and views about temephos and mosquito
control. Fieldworkers noted if temephos was present in water containers. RESULTS:
Some 42.4% of rural and 20.7% of urban households reported no temephos programme
visits within the last 12 months. Overall, 42.0% reported they had temephos
placed in their water containers less than 3 months previously. Fieldworkers
observed temephos in at least one container in 21.1% of households. Recent
temephos application and observed temephos were both significantly more common in
urban households, when other household variables were taken into account; in
rural areas, smaller households were more likely to have temephos present. Most
households (74.4%) did not think bathing with water containing temephos carried
any health risk. Half (51%) believed drinking or cooking with such water could be
harmful and 17.6% were unsure. Significantly fewer households in intervention
sites (16.5%) than in control sites (26.0%) (Risk Difference - 0.095, 95%
confidence interval - 0.182 to -0.009) had temephos observed in their water; more
households in intervention clusters (41.8%) than in control clusters (31.6%)
removed the applied temephos quickly. Although fewer households in intervention
sites (82.7%) compared with control sites (86.7%) (RD -0.04, 95% CI -0.067 to
0.013) agreed temephos and fumigation was the best way to avoid mosquitoes, the
proportion believing this remained very high. CONCLUSION: Coverage with the
government temephos programme was low, especially in rural areas. Despite an
intervention encouraging non-chemical mosquito control, most households continued
to believe that chemicals are the best control method. TRIAL REGISTRATION:
ISRCTN: 27581154 .
PMID- 28699555
TI - Pupal productivity in rainy and dry seasons: findings from the impact survey of a
randomised controlled trial of dengue prevention in Guerrero, Mexico.
AB - BACKGROUND: The follow-up survey of a cluster-randomised controlled trial of
evidence-based community mobilisation for dengue control in Nicaragua and Mexico
included entomological information from the 2012 rainy and dry seasons. We used
data from the Mexican arm of the trial to assess the impact of the community
action on pupal production of the dengue vector Aedes aegypti in both rainy and
dry seasons. METHODS: Trained field workers inspected household water containers
in 90 clusters and collected any pupae or larvae present for entomological
examination. We calculated indices of pupae per person and pupae per household,
and traditional entomological indices of container index, household index and
Breteau index, and compared these between rainy and dry seasons and between
intervention and control clusters, using a cluster t-test to test significance of
differences. RESULTS: In 11,933 houses in the rainy season, we inspected 40,323
containers and found 7070 Aedes aegypti pupae. In the dry season, we inspected
43,461 containers and counted 6552 pupae. All pupae and entomological indices
were lower in the intervention clusters (IC) than in control clusters (CC) in
both the rainy season (RS) and the dry season (DS): pupae per container 0.12 IC
and 0.24 CC in RS, and 0.10 IC and 0.20 CC in DS; pupae per household 0.46 IC and
0.82 CC in RS, and 0.41 IC and 0.83 CC in DS; pupae per person 0.11 IC and 0.19
CC in RS, and 0.10 IC and 0.20 CC in DS; household index 16% IC and 21% CC in RS,
and 12.1% IC and 17.9% CC in DS; container index 7.5% IC and 11.5% CC in RS, and
4.6% IC and 7.1% CC in DS; Breteau index 27% IC and 36% CC in RS, and 19% IC and
29% CC in DS. All differences between the intervention and control clusters were
statistically significant, taking into account clustering. CONCLUSIONS: The trial
intervention led to significant decreases in pupal and conventional entomological
indices in both rainy and dry seasons. TRIAL REGISTRATION: ISRCTN27581154 .
PMID- 28699556
TI - Community-led trials: Intervention co-design in a cluster randomised controlled
trial.
AB - In conventional randomised controlled trials (RCTs), researchers design the
interventions. In the Camino Verde trial, each intervention community designed
its own programmes to prevent dengue. Instead of fixed actions or menus of
activities to choose from, the trial randomised clusters to a participatory
research protocol that began with sharing and discussing evidence from a local
survey, going on to local authorship of the action plan for vector control.Adding
equitable stakeholder engagement to RCT infrastructure anchors the research
culturally, making it more meaningful to stakeholders. Replicability in other
conditions is straightforward, since all intervention clusters used the same
engagement protocol to discuss and to mobilize for dengue prevention. The ethical
codes associated with RCTs play out differently in community-led pragmatic
trials, where communities essentially choose what they want to do. Several
discussion groups in each intervention community produced multiple plans for
prevention, recognising different time lines. Some chose fast turnarounds, like
elimination of breeding sites, and some chose longer term actions like garbage
disposal and improving water supplies.A big part of the skill set for community
led trials is being able to stand back and simply support communities in what
they want to do and how they want to do it, something that does not come
naturally to many vector control programs or to RCT researchers. Unexpected
negative outcomes can come from the turbulence implicit in participatory
research. One example was the gender dynamic in the Mexican arm of the Camino
Verde trial. Strong involvement of women in dengue control activities seems to
have discouraged men in settings where activity in public spaces or outside of
the home would ordinarily be considered a "male competence".Community-led trials
address the tension between one-size-fits-all programme interventions and local
needs. Whatever the conventional wisdom about how prevention works at a system
level, programmes have to be perceived as locally relevant and they must engage
stakeholders who make them work. Locally, each participating community has to
know the intervention is relevant to them; they have to want to do it. That
happens much more easily if they design the programme themselves.
PMID- 28699557
TI - "Where we put little fish in the water there are no mosquitoes:" a cross
sectional study on biological control of the Aedes aegypti vector in 90 coastal
region communities of Guerrero, Mexico.
AB - BACKGROUND: In the Mexican state of Guerrero, some households place fish in water
storage containers to prevent the development of mosquito larvae. Studies have
shown that larvivorous fish reduce larva count in household water containers, but
there is a lack of evidence about whether the use of fish is associated with a
reduction in dengue virus infection. We used data from the follow up survey of
the Camino Verde cluster randomised controlled trial of community mobilisation to
reduce dengue risk to study this association. METHODS: The survey in 2012, among
90 clusters in the three coastal regions of Guerrero State, included a
questionnaire to 10,864 households about socio-demographic factors and self
reported cases of dengue illness in the previous year. Paired saliva samples
provided serological evidence of recent dengue infection among 4856 children aged
3-9 years. An entomological survey in the same households looked for larvae and
pupae of Aedes aegypti and recorded presence of fish and temephos in water
containers. We examined associations with the two outcomes of recent dengue
infection and reported dengue illness in bivariate analysis and then multivariate
analysis using generalized linear mixed modelling. RESULTS: Some 17%
(1730/10,111) of households had fish in their water containers. The presence of
fish was associated with lower levels of recent dengue virus infection in
children aged 3-9 years (OR 0.64; 95% CI 0.45-0.91), as was living in a rural
area (OR 0.57; 95% CI 0.45-0.71), and being aged 3-5 years (OR 0.65; 95% CI 0.51
0.83). Factors associated with lower likelihood of self-reported dengue illness
were: the presence of fish (OR 0.79; 95% CI 0.64-0.97), and living in a rural
area (OR 0.74; 95% CI 0.65-0.84). Factors associated with higher likelihood of
self-reported dengue illness were: higher education level of the household head
(OR 1.28; 95% CI 1.07-1.52), living in a household with five people or less (OR
1.33; 95% CI 1.16-1.52) and household use of insecticide anti-mosquito products
(OR 1.68; 95% CI 1.47-1.92). CONCLUSIONS: Our study suggests that fish in water
containers may reduce the risk of dengue virus infection and dengue illness. This
could be a useful part of interventions to control the Aedes aegypti vector.
PMID- 28699558
TI - Beyond efficacy in water containers: Temephos and household entomological indices
in six studies between 2005 and 2013 in Managua, Nicaragua.
AB - BACKGROUND: A cluster-randomized controlled trial of community mobilisation for
dengue prevention in Mexico and Nicaragua reported, as a secondary finding, a
higher risk of dengue virus infection in households where inspectors found
temephos in water containers. Data from control sites in the preceding pilot
study and the Nicaragua trial arm provided six time points (2005, 2006, 2007 and
2011, 2012, 2013) to examine potentially protective effects of temephos on
entomological indices under every day conditions of the national vector control
programme. METHODS: Three household entomological indicators for Aedes aegypti
breeding were Household Index, Households with pupae, and Pupae per Person. The
primary exposure indicator at the six time points was temephos identified
physically during the entomological inspection. A stricter criterion for exposure
at four time points included households reporting temephos application during the
last 30 days and temephos found on inspection. Using generalized linear mixed
modelling with cluster as a random effect and temephos as a potential fixed
effect, at each time point we examined possible determinants of lower
entomological indicators. RESULTS: Between 2005 and 2013, temephos exposure was
not significantly associated with a reduction in any of the three entomological
indices, whether or not the exposure indicator included timing of temephos
application. In six of 18 multivariate models at the six time points, temephos
exposure was associated with higher entomological indices; in these models, we
could exclude any protective effect of temephos with 95% confidence. CONCLUSION:
Our failure to demonstrate a significant protective association between temephos
and entomological indices might be explained by several factors. These include
ecological adaptability of the vector, resistance of Aedes to the pesticide,
operational deficiencies of vector control programme, or a decrease in preventive
actions by households resulting from a false sense of protection fostered by the
centralized government programme using chemical agents. Whatever the explanation,
the implication is that temephos affords less protection under routine field
conditions than expected from its efficacy under experimental conditions. TRIAL
REGISTRATION: ISRCTN 27581154 .
PMID- 28699559
TI - Aedes aegypti breeding ecology in Guerrero: cross-sectional study of mosquito
breeding sites from the baseline for the Camino Verde trial in Mexico.
AB - BACKGROUND: Understanding the breeding patterns of Aedes aegypti in households
and the factors associated with infestation are important for implementing vector
control. The baseline survey of a cluster randomised controlled trial of
community mobilisation for dengue prevention in Mexico and Nicaragua collected
information about the containers that are the main breeding sites, identified
possible actions to reduce breeding, and examined factors associated with
household infestation. This paper describes findings from the Mexican arm of the
baseline survey. METHODS: In 2010 field teams conducted household surveys and
entomological inspections in 11,995 households from 90 representative communities
in the three coastal regions of Guerrero State, Mexico. We characterized Ae.
aegypti breeding sites and examined the effect of two preventive measures:
temephos application in water containers, and keeping the containers covered. We
examined associations with household infestation, using bivariate and
multivariate analysis adjusted for clustering effects. RESULTS: We conducted
entomological inspections in 11,995 households. Among 45,353 water containers
examined, 6.5% (2958/45,353) were positive for larvae and/or pupae. Concrete
tanks (pilas) and barrels (tambos) together accounted for 74% of pupal
productivity. Both covering water containers and inserting temephos were
independently associated with a lower risk of presence of larvae or pupae, with
the effect of covering (OR 0.22; 95% CIca 0.15-0.27) stronger than that of
temephos (OR 0.66; 95% CIca 0.53-0.84). Having more than four water containers
was associated with household infestation in both rural areas (OR 1.42; 95% CIca
1.17-1.72) and urban areas (1.81; 1.47-2.25), as was low education of the
household head (rural: 1.27; 1.11-1.46, and urban: 1.39; 1.17-1.66). Additional
factors in rural areas were: household head without paid work (1.31; 1.08-1.59);
being in the Acapulco region (1.91; 1.06-3.44); and using anti-mosquito products
(1.27; 1.09-1.47). In urban areas only, presence of temephos was associated with
a lower risk of household infestation (0.44; 0.32-0.60). CONCLUSION: Concrete
tanks and barrels accounted for the majority of pupal productivity. Covering
water containers could be an effective means of Ae. aegypti vector control, with
a bigger effect than using temephos. These findings were useful in planning and
implementing the Camino Verde trial intervention in Mexico.
PMID- 28699560
TI - Dengue occurrence relations and serology: cross-sectional analysis of results
from the Guerrero State, Mexico, baseline for a cluster-randomised controlled
trial of community mobilisation for dengue prevention.
AB - BACKGROUND: The Mexican arm of the Camino Verde trial of community mobilisation
for dengue prevention covered three coastal regions of Guerrero state: Acapulco,
Costa Grande and Costa Chica. A baseline cross-sectional survey provided data for
community mobilisation and for adapting the intervention design to concrete
conditions in the intervention areas. METHODS: Trained field teams constructed
community profiles in randomly selected clusters, based on observation and key
informant interviews. In each household they carried out an entomological
inspection of water containers, collected information on socio-demographic
variables and cases of dengue illness among household members in the last year,
and gathered paired saliva samples from children aged 3-9 years, which were
subjected to ELISA testing to detect recent dengue infection. We examined
associations with dengue illness and recent dengue infection in bivariate and
then multivariate analysis. RESULTS: In 70/90 clusters, key informants were
unable to identify any organized community groups. Some 1.9% (1029/55,723) of the
household population reported dengue illness in the past year, with a higher rate
in Acapulco region. Among children 3-9 years old, 6.1% (392/6382) had serological
evidence of recent dengue infection. In all three regions, household use of anti
mosquito products, household heads working, and households having less than 5
members were associated with self-reported dengue illness. In Acapulco region,
people aged less than 25 years, those with a more educated household head and
those from urban sites were also more likely to report dengue illness, while in
Costa Chica and Costa Grande, females were more likely to report dengue illness.
Among children aged 3-9 years, those aged 3-4 years and those living in Acapulco
were more likely to have evidence of recent dengue infection. CONCLUSIONS: The
evidence from the baseline survey provided important support for the design and
implementation of the trial intervention. The weakness of community leadership
and the relatively low rates of self-reported dengue illness were challenges that
the Mexican intervention team had to overcome. The higher dengue illness
occurrence among women in Costa Grande and Costa Chica may help explain why women
participated more than men in activities during the Camino Verde trial.
PMID- 28699561
TI - Mobilising communities for Aedes aegypti control: the SEPA approach.
AB - : Camino Verde (the Green Way) is an evidence-based community mobilisation tool
for prevention of dengue and other mosquito-borne viral diseases. Its
effectiveness was demonstrated in a cluster-randomised controlled trial conducted
in 2010-2013 in Nicaragua and Mexico. The common approach that brought functional
consistency to the Camino Verde intervention in both Mexico and Nicaragua is
Socialisation of Evidence for Participatory Action (SEPA). In this article, we
explain the SEPA concept and its theoretical origins, giving examples of its
previous application in different countries and contexts. We describe how the
approach was used in the Camino Verde intervention, with details that show
commonalities and differences in the application of the approach in Mexico and
Nicaragua. We discuss issues of cost, replicability and sustainability, and
comment on which components of the intervention were most important to its
success. In complex interventions, multiple components act in synergy to produce
change. Among key factors in the success of Camino Verde were the use of
community volunteers called brigadistas, the house-to-house visits they
conducted, the use of evidence derived from the communities themselves, and
community ownership of the undertaking. Communities received the intervention by
random assignment; dengue was not necessarily their greatest concern. The very
nature of the dengue threat dictated many of the actions that needed to be taken
at household and neighbourhood levels to control it. But within these parameters,
communities exercised a large degree of control over the intervention and
displayed considerable ingenuity in the process. TRIAL REGISTRATION:
ISRCTN27581154 .
PMID- 28699562
TI - Which green way: description of the intervention for mobilising against Aedes
aegypti under difficult security conditions in southern Mexico.
AB - BACKGROUND: Community mobilisation for prevention requires engagement with and
buy in from those communities. In the Mexico state of Guerrero, unprecedented
social violence related to the narcotics trade has eroded most community
structures. A recent randomised controlled trial in 90 coastal communities
achieved sufficient mobilisation to reduce conventional vector density
indicators, self-reported dengue illness and serologically proved dengue virus
infection. METHODS: The Camino Verde intervention was a participatory research
protocol promoting local discussion of baseline evidence and co-design of vector
control solutions. Training of facilitators emphasised community authorship
rather than trying to convince communities to do specific activities. Several
discussion groups in each intervention community generated a loose and evolving
prevention plan. Facilitators trained brigadistas, the first wave of whom
received a small monthly stipend. Increasing numbers of volunteers joined the
effort without pay. All communities opted to work with schoolchildren and for
house-to-house visits by brigadistas. Children joined the neighbourhood vector
control movements where security conditions permitted. After 6 months, a peer
evaluation involved brigadista visits between intervention communities to review
and to share progress. DISCUSSION: Although most communities had no active social
institutions at the outset, local action planning using survey data provided a
starting point for community authorship. Well-known in their own communities,
brigadistas faced little security risk compared with the facilitators who visited
the communities, or with governmental programmes. We believe the training focus
on evidence-based dialogue and a plural community ownership through multiple
design groups were key to success under challenging security conditions. TRIAL
REGISTRATION: ISRCTN27581154 .
PMID- 28699563
TI - The women made it work: fuzzy transitive closure of the results chain in a dengue
prevention trial in Mexico.
AB - BACKGROUND: A modified theory of planned behaviour (acronym CASCADA) proposes
that Conscious knowledge precedes a change in Attitude, which in turn precedes
positive deviations from negative Subjective norms, intention to Change,
perception of Agency to change, Discussion of possible action, and Action itself.
We used this as a results chain to investigate gender-specific behaviour dynamics
in chemical-free dengue prevention. METHODS: Secondary analysis of the Mexican
arm of a cluster randomised controlled trial used household survey data on
intermediate outcomes of dengue prevention behaviour. We used a matrix of odds
ratios between outcomes, transformed to a symmetrical range (-1, 1), to compute
fuzzy transitive closure of the results chain for control and intervention
clusters, then for male and female respondents separately in each group.
Transitive closure of a map computes the influence of each factor on each other
factor, taking account of all influences in the system. Cumulative net influence
was the sum of influences across the results chain. RESULTS: Responses of 5042
women and 1143 men in 45 intervention clusters contrasted with those of 5025
women and 1179 men in 45 control clusters. Control clusters showed a distal block
(negative influence) in the results chain with a cumulative net influence of
0.88; intervention clusters showed no such block and a cumulative net influence
of 1.92. Female control respondents, like the overall control picture, showed a
distal block, whereas female intervention responses showed no such blocks
(cumulative net influence 0.78 and 1.73 respectively). Male control respondents
showed weak distal blocks. Male intervention responses showed several new
negative influences and a reduction of cumulative net influence (1.38 in control
and 1.11 in intervention clusters). CONCLUSIONS: The overall influence of the
intervention across the results chain fits with the trial findings, but is
different for women and men. Among women, the intervention overcame blocks and
increased the cumulative net influence of knowledge on action. Among men, the
intervention did not reinforce prevention behaviour. This might be related to
emphasis, during the intervention, on women's participation and empowerment. The
fuzzy transitive closure of the CASCADA map usefully highlights the differences
between gender-specific results chains. TRIAL REGISTRATION: ISRCTN27581154 .
PMID- 28699564
TI - Detecting clinically relevant new information in clinical notes across
specialties and settings.
AB - BACKGROUND: Automated methods for identifying clinically relevant new versus
redundant information in electronic health record (EHR) clinical notes is useful
for clinicians and researchers involved in patient care and clinical research,
respectively. We evaluated methods to automatically identify clinically relevant
new information in clinical notes, and compared the quantity of redundant
information across specialties and clinical settings. METHODS: Statistical
language models augmented with semantic similarity measures were evaluated as a
means to detect and quantify clinically relevant new and redundant information
over longitudinal clinical notes for a given patient. A corpus of 591 progress
notes over 40 inpatient admissions was annotated for new information
longitudinally by physicians to generate a reference standard. Note redundancy
between various specialties was evaluated on 71,021 outpatient notes and 64,695
inpatient notes from 500 solid organ transplant patients (April 2015 through
August 2015). RESULTS: Our best method achieved at best performance of 0.87
recall, 0.62 precision, and 0.72 F-measure. Addition of semantic similarity
metrics compared to baseline improved recall but otherwise resulted in similar
performance. While outpatient and inpatient notes had relatively similar levels
of high redundancy (61% and 68%, respectively), redundancy differed by author
specialty with mean redundancy of 75%, 66%, 57%, and 55% observed in pediatric,
internal medicine, psychiatry and surgical notes, respectively. CONCLUSIONS:
Automated techniques with statistical language models for detecting redundant
versus clinically relevant new information in clinical notes do not improve with
the addition of semantic similarity measures. While levels of redundancy seem
relatively similar in the inpatient and ambulatory settings in the Fairview
Health Services, clinical note redundancy appears to vary significantly with
different medical specialties.
PMID- 28699565
TI - Household costs of dengue illness: secondary outcomes from a randomised
controlled trial of dengue prevention in Guerrero state, Mexico.
AB - BACKGROUND: Dengue is a serious public health problem with an important economic
impact. This study used data from a cluster randomised controlled trial of
community mobilisation for dengue prevention to estimate the household costs of
treatment of dengue illness. It examined the economic impact of the trial
intervention in the three coastal regions of Mexico's Guerrero State. METHODS:
The 2010 baseline survey covered households in a random sample of 90 clusters in
the coastal regions; the clusters were randomly allocated to intervention or
control and re-surveyed in 2012. The surveys asked about dengue cases in the last
12 months, expenditures on their treatment, and work or school days lost by
patients and care givers. We did not assign monetary value to days lost, since a
lost day to a person of low earning power is of equal or higher value to that
person than to one who earns more. RESULTS: The 12,312 households in 2010
reported 1020 dengue cases in the last 12 months (1.9% of the sample population).
Most (78%) were ambulatory cases, with a mean cost of USD 51 and 10.8 work/school
days, rising to USD 96 and 11.4 work/school days if treated by a private
physician. Hospitalised cases cost USD 28-94 in government institutions and USD
392 in private hospitals (excluding additional inpatient charges), as well as 9.6
17.3 work/school days. Dengue cases cost households an estimated 412,825
work/school days throughout the three coastal regions. In the follow up survey,
6.1% (326/5349) of households in intervention clusters and 7.9% (405/5139) in
control clusters reported at least one dengue case. The mean of days lost per
case was similar in intervention and control clusters, but the number of days
lost from dengue and all elements of costs for dengue cases per 1000 population
were lower in intervention clusters. If the total population of the three coastal
regions had received the intervention, some 149,401 work or school days lost per
year could have been prevented. CONCLUSION: The economic effect of dengue on
households, including lost work days, is substantial. The Camino Verde trial
intervention reduced household costs for treatment of dengue cases. TRIAL
REGISTRATION: The trial was registered as ISRCTN:27,581,154 .
PMID- 28699566
TI - Entity recognition from clinical texts via recurrent neural network.
AB - BACKGROUND: Entity recognition is one of the most primary steps for text analysis
and has long attracted considerable attention from researchers. In the clinical
domain, various types of entities, such as clinical entities and protected health
information (PHI), widely exist in clinical texts. Recognizing these entities has
become a hot topic in clinical natural language processing (NLP), and a large
number of traditional machine learning methods, such as support vector machine
and conditional random field, have been deployed to recognize entities from
clinical texts in the past few years. In recent years, recurrent neural network
(RNN), one of deep learning methods that has shown great potential on many
problems including named entity recognition, also has been gradually used for
entity recognition from clinical texts. METHODS: In this paper, we
comprehensively investigate the performance of LSTM (long-short term memory), a
representative variant of RNN, on clinical entity recognition and protected
health information recognition. The LSTM model consists of three layers: input
layer - generates representation of each word of a sentence; LSTM layer - outputs
another word representation sequence that captures the context information of
each word in this sentence; Inference layer - makes tagging decisions according
to the output of LSTM layer, that is, outputting a label sequence. RESULTS:
Experiments conducted on corpora of the 2010, 2012 and 2014 i2b2 NLP challenges
show that LSTM achieves highest micro-average F1-scores of 85.81% on the 2010
i2b2 medical concept extraction, 92.29% on the 2012 i2b2 clinical event
detection, and 94.37% on the 2014 i2b2 de-identification, which is considerably
competitive with other state-of-the-art systems. CONCLUSIONS: LSTM that requires
no hand-crafted feature has great potential on entity recognition from clinical
texts. It outperforms traditional machine learning methods that suffer from fussy
feature engineering. A possible future direction is how to integrate knowledge
bases widely existing in the clinical domain into LSTM, which is a case of our
future work. Moreover, how to use LSTM to recognize entities in specific formats
is also another possible future direction.
PMID- 28699567
TI - Developing a similarity searching module for patient safety event reporting
system using semantic similarity measures.
AB - BACKGROUND: The most important knowledge in the field of patient safety is
regarding the prevention and reduction of patient safety events (PSE) during
treatment and care. The similarities and patterns among the events may otherwise
go unnoticed if they are not properly reported and analyzed. There is an urgent
need for developing a PSE reporting system that can dynamically measure the
similarities of the events and thus promote event analysis and learning effect.
METHODS: In this study, three prevailing algorithms of semantic similarity were
implemented to measure the similarities of the 366 PSE annotated by the taxonomy
of The Agency for Healthcare Research and Quality (AHRQ). The performance of each
algorithm was then evaluated by a group of domain experts based on a 4-point
Likert scale. The consistency between the scales of the algorithms and experts
was measured and compared with the scales randomly assigned. The similarity
algorithms and scores, as a self-learning and self-updating module, were then
integrated into the system. RESULTS: The result shows that the similarity scores
reflect a high consistency with the experts' review than those randomly assigned.
Moreover, incorporating the algorithms into our reporting system enables a
mechanism to learn and update based upon PSE similarity. CONCLUSION: In
conclusion, integrating semantic similarity algorithms into a PSE reporting
system can help us learn from previous events and provide timely knowledge
support to the reporters. With the knowledge base in the PSE domain, the new
generation reporting system holds promise in educating healthcare providers and
preventing the recurrence and serious consequences of PSE.
PMID- 28699568
TI - Evaluation of the informatician perspective: determining types of research papers
preferred by clinicians.
AB - BACKGROUND: To deliver evidence-based medicine, clinicians often reference
resources that are useful to their respective medical practices. Owing to their
busy schedules, however, clinicians typically find it challenging to locate these
relevant resources out of the rapidly growing number of journals and articles
currently being published. The literature-recommender system may provide a
possible solution to this issue if the individual needs of clinicians can be
identified and applied. METHODS: We thus collected from the CiteULike website a
sample of 96 clinicians and 6,221 scientific articles that they read. We examined
the journal distributions, publication types, reading times, and geographic
locations. We then compared the distributions of MeSH terms associated with these
articles with those of randomly sampled MEDLINE articles using two-sample Z-test
and multiple comparison correction, in order to identify the important topics
relevant to clinicians. RESULTS: We determined that the sampled clinicians
followed the latest literature in a timely manner and read papers that are
considered landmarks in medical research history. They preferred to read
scientific discoveries from human experiments instead of molecular-, cellular- or
animal-model-based experiments. Furthermore, the country of publication may
impact reading preferences, particularly for clinicians from Egypt, India,
Norway, Senegal, and South Africa. CONCLUSION: These findings provide useful
guidance for developing personalized literature-recommender systems for
clinicians.
PMID- 28699569
TI - Leveraging machine learning-based approaches to assess human papillomavirus
vaccination sentiment trends with Twitter data.
AB - BACKGROUND: As one of the serious public health issues, vaccination refusal has
been attracting more and more attention, especially for newly approved human
papillomavirus (HPV) vaccines. Understanding public opinion towards HPV vaccines,
especially concerns on social media, is of significant importance for HPV
vaccination promotion. METHODS: In this study, we leveraged a hierarchical
machine learning based sentiment analysis system to extract public opinions
towards HPV vaccines from Twitter. English tweets containing HPV vaccines-related
keywords were collected from November 2, 2015 to March 28, 2016. Manual
annotation was done to evaluate the performance of the system on the unannotated
tweets corpus. Followed time series analysis was applied to this corpus to track
the trends of machine-deduced sentiments and their associations with different
days of the week. RESULTS: The evaluation of the unannotated tweets corpus showed
that the micro-averaging F scores have reached 0.786. The learning system deduced
the sentiment labels for 184,214 tweets in the collected unannotated tweets
corpus. Time series analysis identified a coincidence between mainstream outcome
and Twitter contents. A weak trend was found for "Negative" tweets that decreased
firstly and began to increase later; an opposite trend was identified for
"Positive" tweets. Tweets that contain the worries on efficacy for HPV vaccines
showed a relative significant decreasing trend. Strong associations were found
between some sentiments ("Positive", "Negative", "Negative-Safety" and "Negative
Others") with different days of the week. CONCLUSIONS: Our efforts on sentiment
analysis for newly approved HPV vaccines provide us an automatic and instant way
to extract public opinion and understand the concerns on Twitter. Our approaches
can provide a feedback to public health professionals to monitor online public
response, examine the effectiveness of their HPV vaccination promotion strategies
and adjust their promotion plans.
PMID- 28699570
TI - Camino Verde (The Green Way): evidence-based community mobilisation for dengue
control in Nicaragua and Mexico: feasibility study and study protocol for a
randomised controlled trial.
AB - BACKGROUND: Since the Aedes aegypti mosquitoes that transmit dengue virus can
breed in clean water, WHO-endorsed vector control strategies place sachets of
organophosphate pesticide, temephos (Abate), in household water storage
containers. These and other pesticide-dependent approaches have failed to curb
the spread of dengue and multiple dengue virus serotypes continue to spread
throughout tropical and subtropical regions worldwide. A feasibility study in
Managua, Nicaragua, generated instruments, intervention protocols, training
schedules and impact assessment tools for a cluster randomised controlled trial
of community-based approaches to vector control comprising an alternative
strategy for dengue prevention and control in Nicaragua and Mexico.
METHODS/DESIGN: The Camino Verde (Green Way) is a pragmatic parallel group trial
of pesticide-free dengue vector control, adding effectiveness to the standard
government dengue control. A random sample from the most recent census in three
coastal regions of Guerrero state in Mexico will generate 90 study clusters and
the equivalent sampling frame in Managua, Nicaragua will generate 60 clusters,
making a total of 150 clusters each of 137-140 households. After a baseline
study, computer-driven randomisation will allocate to intervention one half of
the sites, stratified by country, evidence of recent dengue virus infection in
children aged 3-9 years and, in Nicaragua, level of community organisation.
Following a common evidence-based education protocol, each cluster will develop
and implement its own collective interventions including house-to-house visits,
school-based programmes and inter-community visits. After 18 months, a follow-up
study will compare dengue history, serological evidence of recent dengue virus
infection (via measurement of anti-dengue virus antibodies in saliva samples) and
entomological indices between intervention and control sites. DISCUSSION: Our
hypothesis is that informed community mobilisation adds effectiveness in
controlling dengue. TRIAL REGISTRATION: ISRCTN27581154 .
PMID- 28699571
TI - Irrational "Coefficients" in Renaissance Algebra.
AB - Argument From the time of al-Khwarizmi in the ninth century to the beginning of
the sixteenth century algebraists did not allow irrational numbers to serve as
coefficients. To multiply by x, for instance, the result was expressed as the
rhetorical equivalent of . The reason for this practice has to do with the
premodern concept of a monomial. The coefficient, or "number," of a term was
thought of as how many of that term are present, and not as the scalar multiple
that we work with today. Then, in sixteenth-century Europe, a few algebraists
began to allow for irrational coefficients in their notation. Christoff Rudolff
(1525) was the first to admit them in special cases, and subsequently they appear
more liberally in Cardano (1539), Scheubel (1550), Bombelli (1572), and others,
though most algebraists continued to ban them. We survey this development by
examining the texts that show irrational coefficients and those that argue
against them. We show that the debate took place entirely in the conceptual
context of premodern, "cossic" algebra, and persisted in the sixteenth century
independent of the development of the new algebra of Viete, Decartes, and Fermat.
This was a formal innovation violating prevailing concepts that we propose could
only be introduced because of the growing autonomy of notation from rhetorical
text.
PMID- 28699572
TI - Oriental Metrology and the Politics of Antiquity in Nineteenth-Century Survey
Sciences.
AB - Argument Metrological techniques to establish shared quantitative measures have
often been seen as signs of rational modernization. The cases considered here
show instead the close relation of such techniques with antiquarian and
revivalist programs under imperial regimes. Enterprises in survey sciences in
Egypt in the wake of the French invasion of 1798 and in India during the East
India Company's revenue surveys involved the promotion of a new kind of oriental
metrology designed to represent colonizers' measures as restorations of ancient
values to be applied to current systems of survey and measurement. Surveyors'
practice and hardware help clarify the significance of the complex historical and
political functions of scientific standards. The balance of the paper discusses
the survey work of later nineteenth-century indigenous Egyptian astronomers at a
conjuncture of major economic and political dislocation to explore the various
versions of antiquity at stake in these metrological programs.
PMID- 28699573
TI - The First Jewish Astronomers: Lunar Theory and Reconstruction of a Dead Sea
Scroll.
AB - Argument The Astronomical Book of Enoch describes the passage of the moon through
the gates of heaven, which stand at the edges of the earth. In doing so, the book
describes the position of the rising and setting of the moon on the horizon. Otto
Neugebauer, the historian of ancient science, suggested using the detailed tables
found in later Ethiopic texts in order to reconstruct the path of the moon
through the gates. This paper offers a new examination of earlier versions of the
Astronomical Book, using a mathematical analysis of the figures and astronomical
theories presented throughout the Aramaic Astronomical Book; the results fit both
the data preserved in the scrolls and the mathematical approach and religious
ideology of the scroll's authors better than the details found in the late
Ethiopic texts. Among other new insights, this alternate theory also teaches
about the process of the composition of the Astronomical Book in the first
centuries of its composition.
PMID- 28699574
TI - A New Turn-On Fluorometric Detection Method for the Determination of Ag(I) in
Some Food and Water Samples.
AB - A new sensitive and selective turn-on fluorometry procedure for the determination
of silver using a laboratory-built fluorometry system is described herein. After
synthesis and characterization, a [2-((E)-{[3',6'-bis(ethylamino)-2',7'-dimethyl
3-oxospiro[isoindole-1,9'-xanthen]-2(3H)-yl]imino}methyl)cyclopenta-2,4-dien-1
yl] (cyclopenta-2,4-dien-1-yl)iron (DKMS) fluorescent reagent was used for the
first time. Ag(I) was complexed with the new fluorescent reagent, and direct
measurements were made using fluorometry without any separation/preconcentration.
The fluorescence intensity of the Ag(I)-DKMS complex remained unchanged for over
18 h at room temperature and was a linear function of the concentration of Ag(I)
in the 0-2.5 mg/L range. The optimum determination conditions were established by
testing different reagent quantities, the acidity and pH of the sample, and the
effect of temperature and interfering ions. The LOD of the method was 1.00 MUg/L
whereas the RSD was 0.1% for 0.1 mg/L Ag(I) concentration. "The developed method
was applied successfully for the Ag(I) determination of silver in burn cream,
anode slime, some food and water samples". Results of the analysis of Certified
Reference Materials (NCS DC73349 Bush Branches and Leaves - Trace Elements, and
CWW-TM-D Certified Wastewater and Trace Metals) are in good agreement with the
certified values.
PMID- 28699575
TI - Proposal to reclassify Ehrlichia muris as Ehrlichia muris subsp. muris subsp.
nov. and description of Ehrlichia muris subsp. eauclairensis subsp. nov., a newly
recognized tick-borne pathogen of humans.
AB - We have previously described a novel taxon of the genus Ehrlichia (type strain
WisconsinT), closely related to Ehrlichia muris, that causes human ehrlichiosis
among patients with exposures to ticks in the upper midwestern USA. DNA from this
bacterium was also detected in Ixodes scapularis and Peromyscus leucopus
collected in Minnesota and Wisconsin. To determine the relationship between the
E. muris-like agent (EMLA) and other species of the genus Ehrlichia phenotypic,
genotypic and epidemiologic comparisons were undertaken, including sequence
analysis of eight gene loci (3906 nucleotides) for 39 EMLA DNA samples and the
type strain of E. muris AS145T. Three loci were also sequenced from DNA of nine
strains of E. muris from mouse spleens from Japan. All sequences from E. muris
were distinct from homologous EMLA sequences, but differences between them were
less than those observed among other species of the genus Ehrlichia. Phenotypic
comparison of EMLA and E. muris revealed similar culture and electron microscopic
characteristics, but important differences were noted in their geographic
distribution, ecological associations and behavior in mouse models of infection.
Based on these comparisons, we propose that type strain WisconsinT represents a
novel subspecies, Ehrlichia murissubsp. eauclairensis,subsp. nov. This strain is
available through the Centers for Disease Control and Prevention Rickettsial
Isolate Reference Collection (CRIRC EMU002T) and through the Collection de
Souches de l'Unite des Rickettsies (CSURP2883 T). The subspecies Ehrlichia
murissubsp. muris subsp. nov. is automatically created and the type strain AS145T
is also available through the same collections (CRIRC EMU001T, CSUR E2T).
Included is an emended description of E. muris.
PMID- 28699576
TI - Flavobacterium olei sp. nov., a novel psychrotolerant bacterium isolated from oil
contaminated soil.
AB - During a study of psychrophilic hydrocarbon-degrading bacteria, two yellow, Gram
staining-negative, non-motile, and rod shaped bacteria, designated R-10-9T and K
4-2 were isolated from oil-contaminated soil from Ulaanbaatar, Mongolia. Both
strains were able to grow at 0-32 degrees C, pH 5.0-9.5, and 0-1 % (w/v) NaCl
concentration. These strains were taxonomically characterized by a polyphasic
approach. On the basis of the results of 16S rRNA gene sequence analysis, R-10-9T
and K-4-2 belong to the genus Flavobacterium and are closely related to
Flavobacterium oncorhynchi 631-08T (97.80 and 98.09 % sequence similarity,
respectively). The pairwise sequence similarity between R-10-9T and K-4-2 was
observed to be 99.72 %. In both strains, the predominant respiratory quinone was
menaquinone-6; the major polar lipid was phosphatidylethanolamine; and the major
fatty acids were summed feature 3 (C16 : 1omega7c and/or C16 : 1omega6c), iso-C15
: 0, C16 : 0 3-OH, antesio-C15 : 0, C16 : 0, iso-C17 : 0 3-OH, and iso-C15 : 0 3
OH. The genomic DNA G+C contents of R-10-9T and K-4-2 were 35.9 and 35.4 mol%,
respectively. The DNA-DNA relatedness between R-10-9T and K-4-2 was higher than
70 % but relatedness values with closely related reference strains were less than
35 %. The morphological, physiological, chemotaxonomic, and phylogenetic analyses
clearly distinguished R-10-9T from its closest phylogenetic neighbours. Thus, R
10-9T represents a novel species of the genus Flavobacterium, for which the name
Flavobacterium olei sp. nov. is proposed. The type strain is R-10-9T (=KEMB 9005
447T=KACC 18997T=JCM 31673T), and strain K-4-2 as an additional strain.
PMID- 28699577
TI - Sphingobacteriumsoli sp. nov., isolated from soil.
AB - A Gram-stain-negative, strictly aerobic, rod-shaped, non-motile, non-spore
forming bacterial strain, designated YIM X0211T, was isolated from a soil sample
of Shiling County, Yunnan Province, south-west China. The new isolate was
characterized taxonomically by using a polyphasic approach. The strain grew
optimally at 30 degrees C, at pH 7.0 and with 0-3 % (w/v) NaCl. It was positive
for catalase and oxidase but negative for H2S production. Comparative 16S rRNA
gene sequence analysis showed that strain YIM X0211T fell within the cluster
comprising Sphingobacterium species and clustered with Sphingobacterium mizutaii
DSM 11724T (97.93 % similarity). The G+C content of the genomic DNA was 41.2
mol%. The predominant respiratory quinone was menaquinone MK-7. The major fatty
acids were iso-C15 : 0 2-OH, iso-C17 : 0 3-OH and summed feature 3 (C16 :
1omega7c/C16 : 1omega6c). The polar lipids consisted of phosphatidylethanolamine,
sphingolipid, and several unknown phospholipids or lipids. The DNA-DNA
hybridization value between strain YIM X0211T and S. mizutaii DSM 11724T was
42.3+/-0.4 %, which is below the 70 % limit for species delineation. These
chemotaxonomic data supported the affiliation of strain YIM X0211T to the genus
Sphingobacterium. Based on the recorded phenotypic and genotypic characteristics,
it is determined that the isolate represents a novel species of the genus
Sphingobacterium, for which the name Sphingobacterium soli sp. nov. is proposed.
The type strain is YIM X0211T (=KCTC 42696T=CGMCC 1.15966T).
PMID- 28699578
TI - What is the impact of treatment for hepatitis C virus infection?
PMID- 28699579
TI - Retraction and republication-Effectiveness of non-steroidal anti-inflammatory
drugs for the treatment of osteoarthritis pain: a network meta-analysis.
PMID- 28699580
TI - Offline: Not one day more.
PMID- 28699581
TI - Caring for health in occupied Palestinian territory.
PMID- 28699582
TI - One woman's journey to equity.
PMID- 28699583
TI - Evaluation of doctors in China: imperative changes are required.
PMID- 28699584
TI - Unmet challenges for rehabilitation after stroke in China.
PMID- 28699585
TI - The dilemmas of the European Union's open access to data policy.
PMID- 28699586
TI - Patients' decisions on joint replacement need data on earnings and welfare
benefits.
PMID- 28699588
TI - Department of Error.
PMID- 28699587
TI - Response to what WHO can do to support research in LMICs.
PMID- 28699589
TI - Department of Error.
PMID- 28699590
TI - Department of Error.
PMID- 28699591
TI - Retinal detachment in severe myopia.
PMID- 28699592
TI - Addressing the vulnerability of the global food system.
PMID- 28699593
TI - Where next for UK tobacco control?
PMID- 28699594
TI - An African-driven health agenda.
PMID- 28699595
TI - Effectiveness of non-steroidal anti-inflammatory drugs for the treatment of pain
in knee and hip osteoarthritis: a network meta-analysis.
AB - BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) are the backbone of
osteoarthritis pain management. We aimed to assess the effectiveness of different
preparations and doses of NSAIDs on osteoarthritis pain in a network meta
analysis. METHODS: For this network meta-analysis, we considered randomised
trials comparing any of the following interventions: NSAIDs, paracetamol, or
placebo, for the treatment of osteoarthritis pain. We searched the Cochrane
Central Register of Controlled Trials (CENTRAL) and the reference lists of
relevant articles for trials published between Jan 1, 1980, and Feb 24, 2015,
with at least 100 patients per group. The prespecified primary and secondary
outcomes were pain and physical function, and were extracted in duplicate for up
to seven timepoints after the start of treatment. We used an extension of
multivariable Bayesian random effects models for mixed multiple treatment
comparisons with a random effect at the level of trials. For the primary
analysis, a random walk of first order was used to account for multiple follow-up
outcome data within a trial. Preparations that used different total daily dose
were considered separately in the analysis. To assess a potential dose-response
relation, we used preparation-specific covariates assuming linearity on log
relative dose. FINDINGS: We identified 8973 manuscripts from our search, of which
76 randomised trials with a total of 58 451 patients were included in this
analysis. 23 nodes concerning seven different NSAIDs or paracetamol with specific
daily dose of administration or placebo were considered. All preparations,
irrespective of dose, improved point estimates of pain symptoms when compared
with placebo. For six interventions (diclofenac 150 mg/day, etoricoxib 30 mg/day,
60 mg/day, and 90 mg/day, and rofecoxib 25 mg/day and 50 mg/day), the probability
that the difference to placebo is at or below a prespecified minimum clinically
important effect for pain reduction (effect size [ES] -0.37) was at least 95%.
Among maximally approved daily doses, diclofenac 150 mg/day (ES -0.57, 95%
credibility interval [CrI] -0.69 to -0.45) and etoricoxib 60 mg/day (ES -0.58,
0.74 to -0.43) had the highest probability to be the best intervention, both with
100% probability to reach the minimum clinically important difference. Treatment
effects increased as drug dose increased, but corresponding tests for a linear
dose effect were significant only for naproxen (p=0.034). We found no evidence
that treatment effects varied over the duration of treatment. Model fit was good,
and between-trial heterogeneity and inconsistency were low in all analyses. All
trials were deemed to have a low risk of bias for blinding of patients. Effect
estimates did not change in sensitivity analyses with two additional statistical
models and accounting for methodological quality criteria in meta-regression
analysis. INTERPRETATION: On the basis of the available data, we see no role for
single-agent paracetamol for the treatment of patients with osteoarthritis
irrespective of dose. We provide sound evidence that diclofenac 150 mg/day is the
most effective NSAID available at present, in terms of improving both pain and
function. Nevertheless, in view of the safety profile of these drugs, physicians
need to consider our results together with all known safety information when
selecting the preparation and dose for individual patients. FUNDING: Swiss
National Science Foundation (grant number 405340-104762) and Arco Foundation,
Switzerland.
PMID- 28699597
TI - Predictive factors for endoscopic recurrence after ileocolic resection for
Crohn's disease.
PMID- 28699598
TI - Role of toll-like receptor 10 gene polymorphism and gastric mucosal pattern in
patients with chronic gastritis.
AB - BACKGROUND/AIMS: Helicobacter pylori stimulates the host's toll-like receptors
(TLRs). Single-nucleotide polymorphism (SNP) of TLRs is related to the
manipulation of regulatory cytokines and also implicated in the varied outcomes
of the inflammatory response, including the development of precancerous lesions
of gastric mucosa and disease progression. We hypothesized that TLR10 rs10004195
polymorphism is associated with gastric mucosal patterns. MATERIALS AND METHODS:
TLR10 rs10004195 polymorphisms were identified in a total of 400 gastritis
patients using the TagMan SNP genotyping assay. Gastric mucosal patterns were
classified by Conventional Narrow Band Imaging gastroscopy (C-NBI gastroscopy).
Logistic regression was used to analyze the association. RESULTS: The gastritis
patients was Type 1, 37.5% of Thai patients. The T/T homozygous genotype was
exhibited by the highest percentage (46.5%) of patients, and the A/A homozygous
and A/T heterozygous genotypes were exhibited by 20.25% and 33.25%, respectively,
of patients. TLR10 rs10004195 was significantly associated with gastric mucosal
patterns. After adjusting for confounding factors, patients with the A/A
homozygous genotype showed a significantly increased risk of severe inflammation
(OR=1.35, 95% CI=0.97-2.13, p=0.028). Patients with the A/T heterozygous and T/T
homozygous genotypes showed a significantly increased risk of mild inflammation
(OR=1.24, 95% CI=0.78-2.07, p=0.042 and OR=1.78, 95% CI=0.51-3.35, p=0.001,
respectively). CONCLUSION: Our results indicate that the presence of TLR10
rs10004195, A/T heterozygous, and T/T homozygous genotypes is associated with
type 1, 2, and 3 whereas that of the A/A homozygous genotype is associated with
type 4 and 5 of gastric mucosal patterns. This suggests that the A/A homozygous
genotype contributes to severe inflammation in H. pylori-associated gastritis in
Thai patients.
PMID- 28699599
TI - Significance of selected morphological and histopathological parameters of colon
tumors as prognostic factors of cancer spread.
AB - BACKGROUND/AIMS: The identification of prognostic factors of metastatic
development is one of the most important issues in colorectal cancer (CRC)
research. The aim of this study was to determine the usefulness of colon tumor
characteristics, including location, circumferential location, histological type,
and histological grade, as predictors of metastases. MATERIALS AND METHODS: To
identify potential predictors of CRC spread, we analyzed data of 191 patients who
had undergone surgery for colon tumors. We searched for potential associations
between the location in the right or left colon, circumferential location,
histological type, and histological grade (G-parameter) of colon tumors and the
incidence of lymph node and distal metastases. The analysis was based on
Pearson's chi-square (chi2) test with a statistical significance of p<0.05.
RESULTS: Lymph node metastases were found in 100 patients, including 44 patients
with synchronous liver metastases. Lymph node involvement was detected in 43
(52.4%) patients with right-sided and in 57 (52.3%) patients with left-sided
tumors (p=0.984). Liver metastases were detected in 19 (23.17%) patients with
right-sided colon tumors and in 25 (22.9%) patients with left-sided tumors
(p=0.969). Lymph node and liver metastases were found in 60 (47.6%) and 24
(19.0%) patients with annular tumors, respectively (p=NS), and these were found
on the mesenteric side in 75.0% (n=30) and 20.0% (n=8) patients (p=0.004) and on
the antimesenteric side in 47.6% (n=10) and 48.0% (n=12) patients (p=0.044),
respectively. CONCLUSION: The circumferential location of primary colon tumors is
a significant predictor of their metastatic potential. The mesenteric location of
the tumor is predisposed to lymphatic spread, whereas the antimesenteric location
predicts hematogenous spread.
PMID- 28699600
TI - Extracellular matrix protein 1 gene rs3737240 single nucleotide polymorphism is
associated with ulcerative colitis in Turkish patients.
AB - BACKGROUND/AIMS: Ulcerative colitis (UC) and Crohn's disease are chronic
inflammatory diseases. Genetic, immunologic, and microbial factors play an
important role in their pathogenesis. Extracellular matrix protein 1 (ECM1), a
gene related to mucosal barrier function, has been shown to be associated with
UC. This study aims to determine the relationship between ECM1 gene rs3737240
single nucleotide polymorphism (SNP) and UC in a group of Turkish patients.
MATERIALS AND METHODS: Ninety-four UC patients and 120 healthy controls were
enrolled in the study. ECM1 gene rs3737240 SNP genotyping was performed using the
polymerase chain reaction-restriction fragment length polymorphism method.
RESULTS: TT genotype was significantly more common in UC patients than in the
healthy control group [p=0.034; odds ratio (OR) 2.34; 95% confidence interval
(CI) 1.04-5.25]. The presence of C allele significantly lowered the UC risk
(p=0.034; OR 0.42; 95% CI 0.19-0.95). TT genotype was significantly associated
with azathioprine use in UC patients (p=0.037; OR 3.0; 95% CI 1.04-8.65). The C
allele significantly reduced the probability of azathioprine use in UC patients
(p=0.037; OR 0.33 CI 95% 0.11-0.96). No relation was found between rs3737240 SNP
genotype and the phenotypical characteristics of UC patients. CONCLUSION: The TT
genotype of ECM1 gene rs3737240 SNP significantly increased susceptibility for UC
and azathioprine use in UC patients in a Turkish population.
PMID- 28699601
TI - Role of TNF-alpha -308G/A gene polymorphism in gastric cancer risk: A case
control study and meta-analysis.
AB - BACKGROUND/AIMS: In the Chinese population, gastric cancer (GC) is ranked as the
third most common type of cancer. Although the exact etiology of GC development
is unclear, several factors, including genetic and environmental, have been
identified as risk factors. Variations in cytokine genes and their receptors have
been related to a higher risk of GC. A single nucleotide polymorphism in the
promoter region of tumor necrosis factor-alpha (TNF-alpha) (-308G>A) has been
associated with a higher risk of GC and in the present study we evaluated its
possible association with GC in a Chinese cohort. In addition, we performed a
meta-analysis to draw a firm conclusion about the association between TNF-alpha
gene polymorphisms and GC. MATERIALS AND METHODS: We enrolled 400 Chinese GC
patients and matched healthy controls hailing from similar geographical areas.
The TNF-alpha -308G/A polymorphism was genotyped by allele-specific polymerase
chain reaction (AS-PCR). For the meta-analysis, earlier published articles were
searched and eligible studies were included. RESULTS: Prevalence of the
heterozygous mutant (GA) and minor allele (A) were significantly higher in GC
cases compared to healthy controls (GA: p<0.0001, odds ratio (OR)=4.90; A:
p<0.0001, OR=2.84). A total of 36 eligible studies including the present report,
encompassing of 8353 GC patients and 12099 controls, were analyzed for the meta
analysis. A significant association of the TNF-alpha polymorphism (-308G>A) with
susceptibility to GC was only found in the Caucasian population (A vs G: p=0.001;
AA vs GG: p=0.01; AG vs GG: p<0.0001; AA vs AG+GG: p=0.01; AA+AG vs p=0.003).
CONCLUSION: The results of the present case control study and meta-analysis
showed that associations between TNF-a variants with susceptibility to GC
development is population and ethnic specific.
PMID- 28699602
TI - Importance of target calorie intake in hospitalized patients.
AB - BACKGROUND/AIMS: To evaluate the feasibility and clinical outcome of a
nutritional algorithm based on target calorie intake commenced as enteral
nutrition (EN) alone or in combination with supplemental parenteral nutrition
(SPN) among hospitalized patients. MATERIALS AND METHODS: In total, 301
hospitalized patients who were provided with nutritional support, including EN
(n=125) or EN+SPN (n=176), due to various medical conditions during their
hospitalization were included in this study conducted at Antalya Training and
Research Hospital. All the patients were evaluated during their hospitalization
under nutritional support until discharge or in-hospital death. Data on the
length of stay (LOS) and serum pre-albumin and C-reactive protein (CRP) levels
and records for feeding days considering nutritional risk screening (NRS) 2002
scores were collected. RESULTS: Overall, 85.7% of patients achieved the target
calorie intake within a median of 4.0 days, while discharge and in-hospital death
rates were 58.1% and 41.9%, respectively. Of the 5719 feeding days recorded
during follow-up, 1076 (18.8%) days were associated with failure to achieve the
target calorie intake with hemodynamic instability (33.3%), procurement problems
(33.3%), and oral reluctance (23.0%). CONCLUSION: Our findings emphasize the role
of keeping the intake closer to the target calorie intake and immediate use of
SPN whenever full EN fails to achieve the target calorie intake for improving the
adequacy of clinical nutrition in the early phase of critical illness. The EN and
EN+SPN groups were found to be similar in terms of rates of target achievement,
mortality, and discharge, while a lower mortality rate and improved nutritional
status were evident in achievers than in non-achievers of the target calorie
intake regardless of the type of nutrition.
PMID- 28699603
TI - Infants with extrahepatic biliary atresia: Effect of follow-up on the survival
rate at Ege University Medical School transplantation center.
AB - BACKGROUND/AIMS: Biliary atresia (BA) is the main cause of neonatal cholestasis
and the primary reason for infant liver transplants worldwide. It is an
obliterative cholangiopathy observed only in children and caused by progressive
inflammation and fibrosis of the bile duct. We collaborated with a liver
transplantation center to investigate the effects of follow-up in patients with
BA. MATERIALS AND METHODS: Medical records of 99 patients who were diagnosed with
BA and monitored at our center from 1990 to 2002 (27 patients) and from 2003 to
2015 (72 patients) were analyzed retrospectively. Patients were evaluated for
birth weight; age at jaundice onset; age at alcoholic stool detection; age at the
time of Kasai portoenterostomy (KPE), if performed; age at admission to our
center; age at liver transplantation; duration between KPE and transplantation;
pediatric end-stage liver disease (PELD) scores during transplantation; and
growth and developmental status. The periods 1990-2002 and 2003-2015 were defined
as phases I and II, respectively. RESULTS: The median age of the patients at
presentation to our hospital was 149 (range: 20-730) days during phase I and 61
(range: 28-720) days during phase II. The median age at jaundice onset was 7
days, and the median age at alcoholic stool detection was 15 days. There was no
significant difference between phases I and II in terms of age at jaundice onset,
age at alcoholic stool detection, or birth weight. Twenty-five (92.5%) of the 27
patients in the phase I group were admitted to our center after undergoing KPE.
Forty-four (61.1%) of the 72 patients in the phase II group (median age at the
time of KPE: 47 days) were operated at our center. Median ages of the patients at
the time of KPE at our center were 67.5 (range: 25-220) and 47 (range: 28-139)
days during phases I and II, respectively. The median age of the 28 patients who
were transferred from another center was 70 (range: 45-105) days during phase II.
Liver transplantation was performed in 55 of 99 patients (55.5%). Significant
differences were observed in the age at transplantation, duration between KPE and
transplantation, and PELD scores between patients with BA who underwent KPE at
our center and who underwent KPE at other institutes from other institutes.
CONCLUSION: These findings demonstrate the importance of a timely diagnosis of BA
and undergoing KPE before malnutrition and/or cirrhosis deteriorate the patient's
health. Furthermore, follow-up of patients with BA at a liver transplantation
center increased the success of KPE and improved survival rates.
PMID- 28699604
TI - Torsion of a wandering spleen in an adolescent with Gaucher disease.
AB - A wandering spleen is a rare condition characterized by the malposition of the
spleen due to laxity or absence of its supporting ligaments. Although Gaucher
disease generally presents with massive splenomegaly, which one of the
predisposing causes of a wandering spleen, literature shows only one report of a
wandering spleen in a child with Gaucher disease. In this case presentation, a 13
year-oldadolescent with Gaucher disease on enzyme replacement treatment was
presented, who was detected having an abdominal mass on a routine visit and
diagnosed with partial torsion of a wandering spleen associated with left lobe
hypoplasia of the liver.
PMID- 28699605
TI - Preventive care in inflammatory bowel disease.
PMID- 28699606
TI - An extremely rare cause of acute abdomen.
PMID- 28699607
TI - Retrograde gastroesophageal intussusception: an exceedingly rare complication of
Heller myotomy in a patient with achalasia cardia.
PMID- 28699608
TI - Dyskeratosis congenita, bone marrow failure, and gastric adenocarcinoma: an
insight into telomere biology.
PMID- 28699609
TI - Fluid resuscitation in acute pancreatitis.
PMID- 28699610
TI - Survival and Recovery in Severely Wasted Under-five Children Without Community
Management of Acute Malnutrition Programme.
AB - OBJECTIVE: To evaluate recovery and survival of severely wasted children without
community management of acute malnutrition programme. DESIGN: Single time point
follow-up (24th December 2013 - 2nd April, 2014) of severely wasted children
identified in a community-based cross-sectional survey (September 2012 - October
2013). SETTING: Rural Meerut District, Uttar Pradesh, India. PARTICIPANTS: 409
severely wasted (WHO weight-for-height <-3Z), 6- to 59-month-old children.
OUTCOME MEASURES: Survival and recovery (weight-for-height >=-2Z). RESULTS:
Median (IQR) follow-up contact duration was 7.4 (6.6, 10.1) months. Among 11
deaths, there were 5 (case-fatality 1.2%), 6 (1.5%), 8 (2.0%) and 10 (2.4%)
events within 1, 1.5, 4 and 6 months of enrolment, respectively. Ten deaths
occurred in children aged between 6 and 24 months. Younger age (P=0.04), poorer
household-head occupation (P=0.04) and lower enrolment anthropometry (any
variable; P<0.001) were significant predictors of mortality. Children below 18
months of age had higher adjusted mortality risk (HR 4.7; 95% CI 0.95, 22.51;
P=0.053). At follow-up, 30% of survivors were still severely wasted, 39% were
moderately wasted (weight-for-height -3 to <-2Z) and 31% had recovered
spontaneously. Younger age (P<0.001), female gender (P=0.04) and longer follow-up
duration (P=0.003) were significant independent predictors of recovery. The
adjusted OR (95% CI) for recovery <24 months was 2.81 (1.70, 4.65). CONCLUSION:
Without community management of acute malnutrition in rural Meerut District,
severely wasted children had low (1.2%-2.7%) case-fatality with long-term
spontaneous recovery of around 25-30%.
PMID- 28699611
TI - Impact of High-flow Nasal Cannula Therapy in Quality Improvement and Clinical
Outcomes in a Non-invasive Ventilation Device-free Pediatric Intensive Care Unit.
AB - OBJECTIVE: To analyze the change in quality indicators due to the use of high
flow nasal cannula therapy as a non-invasive ventilation method in children with
respiratory distress/failure in a non-invasive ventilation device-free pediatric
intensive care unit. METHODS: Retrospective chart review of children with
respiratory distress/failure admitted 1 year before (period before high-flow
nasal cannula therapy) and 1 year after (period after high-flow nasal cannula
therapy) the introduction of high-flow nasal cannula therapy. We compared quality
indicators as rate of mechanical ventilation, total duration of mechanical
ventilation, rate of re-intubation, pediatric intensive care unit length of stay,
and mortality rate between these periods. RESULTS: Between November 2012 and
November 2014, 272 patients: 141 before and 131 after high-flow nasal cannula
therapy were reviewed (median age was 20.5 mo). Of the patients in the severe
respiratory distress/failure subgroup, the rate of intubation was significantly
lower in period after than in period before high-flow nasal cannula therapy group
(58.1% vs. 76.1%; P <0.05). The median pediatric intensive care unit length of
stay was significantly shorter in patients who did not require mechanical
ventilation in the period after than in the period before high-flow nasal cannula
therapy group (3d vs. 4d; P<0,05). CONCLUSION: Implementation of high-flow nasal
cannula therapy in pediatric intensive care unit significantly improves the
quality of therapy and its outcomes.
PMID- 28699612
TI - Relationship Between Immune Parameters and Non-alcoholic Fatty Liver Disease in
Obese Children.
AB - OBJECTIVE: To investigate the relationship between immune parameters and non
alcoholic fatty liver disease (NAFLD) in obese children. DESIGN: Cross-sectional
study. SETTING: Hospital-based study in Zhejiang Province, China between July to
September 2015. PARTICIPANTS: A total of 117 obese children and 209 healthy non
obese children were studied as the obese and control groups. Depending on the
severity of NAFLD, the obese group was divided into subgroups 1 (without NAFLD),
2 (with simple fatty liver) and 3 (with steatohepatitis). OUTCOME MEASURES:
Glucose metabolism, lipid metabolism and immune parameters. RESULTS: In the obese
group, body mass index (BMI), waist-and hip-circumferences, fasting insulin,
Homeostasis model of assessment for insulin resistance (HOMA-IR), triglyceride,
total cholesterol, low density lipoprotein cholesterol (LDL-C), apolipoprotein
(Apo)B/ApoA1, alanine aminotransferase, uric acid, white blood cells, neutrophils
percentage, platelet and interleukin (IL)-6 were significantly higher than those
in the controls (P<0.05), while lower high density lipoprotein cholesterol and
lymphocyte percentage were noted (P<0.05). IL-10 in the subgroup 3 was higher
than those in the control group, subgroup 1 and 2 (P<0.05). Logistic regression
analysis showed that BMI, LDL-C, HOMA-IR and IL-10 were independent factors of
NAFLD (P<0.05). CONCLUSION: These results support a low-grade chronic
inflammation in obese children. Moreover, obesity, dyslipidaemia and IR are risk
factors while IL-10 may be a protective factor for NAFLD.
PMID- 28699613
TI - Profile of Bullies and Victims Among Urban School-going Adolescents in Gujarat.
AB - OBJECTIVE: To assess the prevalence of bullying, identifying bullies, victims and
their associations. Methods: Questionnaire having 'Peer Interaction in Primary
Schools' and 'Strength and Difficulty Questionnaire' scales, and demographic
information was administered to 7th, 8th and 9th graders (N=1106). RESULTS:
Prevalence of bullying was 49%. Boys were more likely to be bullies (P=0.03),
whereas students having less friends (P=0.001), overweight/obese (P=0.02), and
boys (P<0.001) were more likely to be victims. Association between bullying
behavior and poor academic performance was noted. CONCLUSION: We found high
prevalence of bullying. The reasons for the same and scope of intervention needs
further study.
PMID- 28699614
TI - Clinical Presentation and Cardiovascular Outcome in Complete versus Incomplete
Kawasaki Disease.
AB - OBJECTIVE: To compare the demographic, clinical, and laboratory features of
incomplete and complete presentations of Kawasaki disease. METHODS: A
retrospective review of the electronic case records between January 2000 and
December 2015 in a tertiary care referral center of Sohar, Oman. RESULTS: 31 out
of 64 children (48.4%) had incomplete presentation. Children with incomplete
presentation had higher incidence of skin rash, lymphadenopathy and
conjunctivitis. They took a longer time to show clinical response to intravenous
immunoglobulin [mean (SD) 52.6 (17.4) h vs 40.1 (16.4) h, P=0.005], and had
prolonged hospitalization [mean (SD) 6.2 (2.5) d vs 4.6 (1.7) d, P=0.009].
CONCLUSION: Children with incomplete presentation of Kawasaki disease tend to
have prolonged hospitalization but short- and long-term coronary outcomes appear
to be similar.
PMID- 28699615
TI - Adiponectin, Interleukin-6 and High-sensitivity C-reactive Protein Levels in
Overweight/Obese Indian children.
AB - OBJECTIVE: The aim of our study was to assess serum Adiponectin, Interleukin-6
(IL-6) and high-sensitivity C-reactive protein (hsCRP) levels and their
correlation with conventional risk factors for cardiovascular disease and
diabetes in overweight/obese Indian children. METHODS: Body mass index (BMI),
waist circumference, blood pressure, fasting serum adiponectin, IL-6, hsCRP,
blood glucose, triglycerides, and total and high density lipoprotein cholesterol
were measured in children aged 7-15 years with BMI >85th centile. RESULTS: 84
overweight/obese children (48 boys) with mean (SD) age 10.2 (1.9) years were
enrolled. Mean (SD) adiponectin, hsCRP and median (IQR) IL-6 levels were 6.0
(3.1) ug/mL, 3.4 (2.4) mg/L and 12.7 (5.0-90.0) pg/mL, respectively. Low
adiponectin, high hsCRP and high IL-6 were noted in 16.5%, 49.4% and 54.4%
participants, respectively. Adiponectin was inversely correlated with waist
circumference, and IL-6 positively with BMI and blood glucose. CONCLUSION:
Inflammatory mediators, hsCRP and IL-6 were elevated in half of the overweight
children. Adiponectin and IL-6 correlated well with traditional risk markers.
PMID- 28699616
TI - Levamisole in Frequently-relapsing and Steroid-dependent Nephrotic Syndrome.
AB - OBJECTIVE: To evaluate the efficacy of levamisole in children with frequently
relapsing nephrotic syndrome (FRNS) and steroid dependent nephrotic syndrome
(SDNS) when administered on an alternate day ('initial therapy' in all cases) or
daily basis ('rescue therapy' in whom alternate day therapy failed). METHODS: The
records of 95 children (age 1-18y) with FRNS (62) and SDNS (33), who were treated
at the Pediatric nephrology clinic, and received levamisole therapy (maximum 2 y
duration, between 2010-2013) with a follow-up period of minimum 1 y, were
included. RESULTS: Alternate day levamisole therapy was efficacious in 73.7%
(n=70). The overall efficacy of levamisole therapy was 88.4% (n=84). Levamisole
therapy decreased the mean (SD) number of relapses from 4.22 (0.46)/y to 1.35
(0.36)/y (P<0.01); and cumulative median (IQR) prednisolone dosage from 4200
(3200-4300) mg/m2 to 1100 (IQR 500-2900) mg/m2 (P<0.001). On a one-year follow up
of the cases in whom levamisole therapy was efficacious during therapy (median 24
mo) (n=84), a frequently relapsing or steroid dependent course continued to
persist in 48.8% (41), necessitating oral cyclophosphamide (n= 22) or
mycophenolate mofetil (n=19). CONCLUSION: Daily levamisole therapy was useful in
56% of children who demonstrated failure while on alternate day levamisole
therapy, and could be a useful therapeutic option in FRNS and SDNS.
PMID- 28699617
TI - Effect of bone-soft tissue friction on ultrasound axial shear strain
elastography.
AB - Bone-soft tissue friction is an important factor affecting several
musculoskeletal disorders, frictional syndromes and the ability of a bone
fracture to heal. However, this parameter is difficult to determine using non
invasive imaging modalities, especially in clinical settings. Ultrasound axial
shear strain elastography is a non-invasive imaging modality that has been used
in the recent past to estimate the bonding between different tissue layers. As
most elastography methods, axial shear strain elastography is primarily used in
soft tissues. More recently, this technique has been proposed to assess the bone
soft tissue interface. In this paper, we investigate the effect of a variation in
bone-soft tissue friction coefficient in the resulting axial shear strain
elastograms. Finite element poroelastic models of bone specimens exhibiting
different bone-soft tissue friction coefficients were created and mechanically
analyzed. These models were then imported to an ultrasound elastography
simulation module to assess the presence of axial shear strain patterns. In vitro
experiments were performed to corroborate selected simulation results. The
results of this study show that the normalized axial shear strain estimated at
the bone-soft tissue interface is statistically correlated to the bone-soft
tissue coefficient of friction. This information may prove useful to better
interpret ultrasound elastography results obtained in bone-related applications
and, possibly, monitor bone healing.
PMID- 28699618
TI - Direct observation of temperature-driven magnetic symmetry transitions by
vectorial resolved MOKE magnetometry.
AB - Angle- and temperature-dependent vectorial magnetometry measurements are
necessary to disentangle the effective magnetic symmetry in magnetic
nanostructures. Here we present a detailed study on an Fe(1 0 0) thin film system
with competing collinear biaxial (four-fold symmetry) and uniaxial (two-fold)
magnetic anisotropies, carried out with our recently developed full angular/broad
temperature range/vectorial-resolved magneto-optical Kerr effect magnetometer,
named TRISTAN. The data give direct views on the angular and temperature
dependence of the magnetization reversal pathways, from which characteristic
axes, remanences, critical fields, domain wall types, and effective magnetic
symmetry are obtained. In particular, although the remanence shows four-fold
angular symmetry for all investigated temperatures (15 K-400 K), the critical
fields show strong temperature and angular dependencies and the reversal
mechanism changes for specific angles at a given (angle-dependent) critical
temperature, showing signatures of an additional collinear two-fold symmetry.
This symmetry-breaking is more relevant as temperature increases to room
temperature. It originates from the competition between two anisotropy
contributions with different symmetry and temperature evolution. The results
highlight the importance of combining temperature and angular studies, and the
need to look at different magnetic parameters to unravel the underlying magnetic
symmetries and temperature evolutions of the symmetry-breaking effects in
magnetic nanostructures.
PMID- 28699619
TI - Highly defined 3D printed chitosan scaffolds featuring improved cell growth.
AB - The augmented demand for medical devices devoted to tissue regeneration and
possessing a controlled micro-architecture means there is a need for industrial
scale-up in the production of hydrogels. A new 3D printing technique was applied
to the automation of a freeze-gelation method for the preparation of chitosan
scaffolds with controlled porosity. For this aim, a dedicated 3D printer was
built in-house: a preliminary effort has been necessary to explore the printing
parameter space to optimize the printing results in terms of geometry, tolerances
and mechanical properties of the product. Analysed parameters included viscosity
of the starting chitosan solution, which was measured with a Brookfield
viscometer, and temperature of deposition, which was determined by filming the
process with a cryocooled sensor thermal camera. Optimized parameters were
applied to the production of scaffolds from solutions of chitosan alone or with
the addition of raffinose as a viscosity modifier. Resulting hydrogels were
characterized in terms of morphology and porosity. In vitro cell culture studies
comparing 3D printed scaffolds with their homologous produced by solution casting
evidenced an improvement in biocompatibility deriving from the production
technique as well as from the solid state modification of chitosan stemming from
the addition of the viscosity modifier.
PMID- 28699620
TI - Aerodynamics and flow features of a damselfly in takeoff flight.
AB - Flight initiation is fundamental for survival, escape from predators and lifting
payload from one place to another in biological fliers and can be broadly
classified into jumping and non-jumping takeoffs. During jumping takeoffs, the
legs generate most of the initial impulse. Whereas the wings generate most of the
forces in non-jumping takeoffs, which are usually voluntary, slow, and stable. It
is of great interest to understand how these non-jumping takeoffs occur and what
strategies insects use to generate large amount of forces required for this
highly demanding flight initiation mode. Here, for the first time, we report
accurate wing and body kinematics measurements of a damselfly during a non
jumping takeoff. Furthermore, using a high fidelity computational fluid dynamics
simulation, we identify the 3D flow features and compute the wing aerodynamics
forces to unravel the key mechanisms responsible for generating large flight
forces. Our numerical results show that a damselfly generates about three times
its body weight during the first half-stroke for liftoff. In generating these
forces, the wings flap through a steeply inclined stroke plane with respect to
the horizon, slicing through the air at high angles of attack (45 degrees -50
degrees ). Consequently, a leading edge vortex (LEV) is formed during both the
downstroke and upstroke on all the four wings. The formation of the LEV, however,
is inhibited in the subsequent upstrokes following takeoff. Accordingly, we
observe a drastic reduction in the magnitude of the aerodynamic force, signifying
the importance of LEV in augmenting force production. Our analysis also shows
that forewing-hindwing interaction plays a favorable role in enhancing both lift
and thrust production during takeoff.
PMID- 28699621
TI - Temperature behaviour of the average size of nanoparticle lattices co-deposited
with an amorphous matrix. Analysis of Ge + Al2O3 and Ni + Al2O3 thin films.
AB - We theoretically interpret the thermal behaviour of the average radius versus
substrate temperature of regular quantum dot/nanocluster arrays formed by
sputtering semiconductor/metal atoms with oxide molecules. The analysis relies on
a continuum theory for amorphous films with given surface quantities, perturbed
by a nanoparticle lattice. An account of the basic thermodynamic contributions is
given in terms of force-flux phenomenological coefficients of each phase (Ge, Ni,
Al2O3). Average radii turn out to be expressible by a characteristic length scale
and a dimensionless parameter, which mainly depend upon temperature through
diffusion lengths, film pressures and finite-size corrections to interfacial
tensions. The numerical agreement is good in both Ge ([Formula: see text]) and Ni
([Formula: see text]) lattices grown at temperatures [Formula: see text]800 K,
despite the lower temperature behaviour of quantum dots seeming to suggest
further driving forces taking part in such processes.
PMID- 28699622
TI - Atom probe tomographic assessment of the distribution of germanium atoms
implanted in a silicon matrix through nano-apertures.
AB - Ion implantation through nanometer-scale apertures (nano-apertures) is a
promising method to precisely position ions in silicon matrices, which is a
requirement for next generation electronic and quantum computing devices. This
paper reports the application of atom probe tomography (APT) to investigate the
three-dimensional distribution of germanium atoms in silicon after implantation
through nano-aperture of 10 nm in diameter, for evaluation of the amount and
spatial distribution of implanted dopants. The experimental results obtained by
APT are consistent with a simple simulation with consideration of several effects
during lithography and ion implantation, such as channeling and resist flow.
PMID- 28699623
TI - Spin-orbit interaction and Kondo scattering at the PrAlO3/SrTiO3 interface:
effects of oxygen content.
AB - We report the effects of oxygen pressure during growth ([Formula: see text]) on
the electronic and magnetic properties of PrAlO3 films grown on [Formula: see
text]-terminated SrTiO3 substrates. Resistivity measurements show an increase in
the sheet resistance as [Formula: see text] is increased. The saturation of the
sheet resistance down to 0.3 K is consistent with Kondo theory for [Formula: see
text] torr. Resistivity data fits indicate Kondo temperatures of 16-18 K. For the
[Formula: see text] sample, we measured a moderate positive magnetoresistance
(MR) due to a strong spin-orbit (SO) interaction at low magnetic fields that
evolves into a larger negative MR at high fields due to the Kondo effect.
Analysis of the MR data permitted the extraction of the SO interaction critical
field for the [Formula: see text] torr interface ([Formula: see text] T). We
observed high positive MR for the least oxygenated sample, where a fraction of
the n-type carriers are derived from oxygen vacancies and possible cation
interdiffusion; for this [Formula: see text] torr sample, Hall effect data
indicate a thick conducting layer. Its extremely high MR (~[Formula: see text])
is attributed to classical behavior due to a distribution of mobilities.
PMID- 28699624
TI - Line tension effects on the wetting of nanostructures: an energy method.
AB - The superhydrophobicity and self-cleaning property of micro/nano-structured solid
surfaces require a stable Cassie-Baxter (CB) wetting state at the liquid-solid
interface. We present an energy method to investigate how the three-phase line
tension affects the CB wetting state on nanostructured materials. For some
nanostructures, the line tension may engender a distinct energy barrier, which
restricts the position of the three-phase contact line and affects the stability
of the CB wetting state. We ascertain the upper and lower limits of the critical
pressure at the CB-Wenzel transition. Our results suggest that
superhydrophobicity on nanostructures can be modulated by tailoring the line
tension and harnessing the curvature effect. This study also provides new
insights into the sinking phenomena observed in the nanoparticle-floating
experiment.
PMID- 28699625
TI - Mutation supply and the repeatability of selection for antibiotic resistance.
AB - Whether evolution can be predicted is a key question in evolutionary biology.
Here we set out to better understand the repeatability of evolution, which is a
necessary condition for predictability. We explored experimentally the effect of
mutation supply and the strength of selective pressure on the repeatability of
selection from standing genetic variation. Different sizes of mutant libraries of
antibiotic resistance gene TEM-1 beta-lactamase in Escherichia coli, generated by
error-prone PCR, were subjected to different antibiotic concentrations. We
determined whether populations went extinct or survived, and sequenced the TEM
gene of the surviving populations. The distribution of mutations per allele in
our mutant libraries followed a Poisson distribution. Extinction patterns could
be explained by a simple stochastic model that assumed the sampling of beneficial
mutations was key for survival. In most surviving populations, alleles containing
at least one known large-effect beneficial mutation were present. These genotype
data also support a model which only invokes sampling effects to describe the
occurrence of alleles containing large-effect driver mutations. Hence, evolution
is largely predictable given cursory knowledge of mutational fitness effects, the
mutation rate and population size. There were no clear trends in the
repeatability of selected mutants when we considered all mutations present.
However, when only known large-effect mutations were considered, the outcome of
selection is less repeatable for large libraries, in contrast to expectations. We
show experimentally that alleles carrying multiple mutations selected from large
libraries confer higher resistance levels relative to alleles with only a known
large-effect mutation, suggesting that the scarcity of high-resistance alleles
carrying multiple mutations may contribute to the decrease in repeatability at
large library sizes.
PMID- 28699626
TI - In Vitro and In Vivo Investigation of High-Intensity Focused Ultrasound (HIFU)
Hat-Type Ablation Mode.
AB - BACKGROUND The aim of this study was to investigate the feasibility of the
application of high-intensity focused ultrasound (HIFU) hat-type ablation mode in
in vitro and in vivo models, and to compare the ablation effects of different
parameter combinations. MATERIAL AND METHODS HIFU hat-type ablation was performed
in isolated bovine liver tissue and in the liver tissue in living rabbits, and
the coagulative necrosis for different parameter combinations (plane angles and
irradiation order) was investigated. We also analyzed and compared the ablation
effects of traditional ablation and hat-type ablation modes. Coagulative necrosis
morphology was detected with TTC staining, and the coagulative necrosis volume
and energy efficiency factor (EEF) were calculated and compared. RESULTS
Coagulative necrosis was observed in all the ablated groups, and the coagulative
necrosis volume was much larger than the irradiation area. The coagulative
necrosis induced by the hat-type ablation was more regular and controllable than
the traditional ablation. The angles between the ablation planes determined the
coagulative necrosis morphology, but did not affect the coagulative necrosis
volume. Moreover, the irradiation order significantly influenced the coagulative
necrosis. Importantly, under certain conditions, hat-type ablation achieved
higher efficiency compared with the traditional ablation mode. CONCLUSIONS
Compared with the traditional ablation mode, HIFU hat-type ablation effectively
shortened the irradiation time, reduced the over-accumulation of energy, and
increased the HIFU ablation efficiency.
PMID- 28699627
TI - Nano-palladium is a cellular catalyst for in vivo chemistry.
AB - Palladium catalysts have been widely adopted for organic synthesis and diverse
industrial applications given their efficacy and safety, yet their biological in
vivo use has been limited to date. Here we show that nanoencapsulated palladium
is an effective means to target and treat disease through in vivo catalysis.
Palladium nanoparticles (Pd-NPs) were created by screening different Pd compounds
and then encapsulating bis[tri(2-furyl)phosphine]palladium(II) dichloride in a
biocompatible poly(lactic-co-glycolic acid)-b-polyethyleneglycol platform. Using
mouse models of cancer, the NPs efficiently accumulated in tumours, where the Pd
NP activated different model prodrugs. Longitudinal studies confirmed that
prodrug activation by Pd-NP inhibits tumour growth, extends survival in tumour
bearing mice and mitigates toxicity compared to standard doxorubicin
formulations. Thus, here we demonstrate safe and efficacious in vivo catalytic
activity of a Pd compound in mammals.
PMID- 28699628
TI - The effects of partial sleep restriction and altered sleep timing on olfactory
performance.
AB - Olfaction can increase the drive to eat and may partially explain the consistent
increases in energy intake (EI) following sleep restriction. We investigated the
effects of 50% sleep restriction with altered sleep timing on olfactory
performance. We also evaluated whether changes (Delta) in olfactory performance
were associated with Delta24 h EI. Twelve men and six women (age: 23+/-4 years;
BMI: 23+/-3 kg/m2) completed three randomized cross-over conditions: habitual
sleep duration, 50% sleep restriction with advanced wake-time, and 50% sleep
restriction with delayed bedtime. Sleep was measured in-laboratory
(polysomnography). Olfactory performance ('sniffin sticks') and 24 h EI (food
menu) were evaluated the next day. A trend for a significant condition*sex
interaction was noted for threshold-discrimination-identification (TDI) scores
(P=0.09); TDI scores were lowest in women and highest in men, following sleep
restriction with advanced wake-time. Deltaolfactory performance were not
associated with Delta24 h EI. The impact of sleep restriction on olfactory
performance may differ between sexes. Changes in olfactory performance were not
associated with changes in 24 h EI. Studies investigating prolonged effects of
sleep loss on the relationship between olfactory performance with EI are needed.
PMID- 28699629
TI - Dietary intake of antioxidant vitamins and risk of stroke: the Japan Public
Health Center-based Prospective Study.
AB - BACKGROUND/OBJECTIVES: Epidemiologic evidence on the relationship between
antioxidant vitamin intake and stroke is limited. We aimed to investigate the
association between dietary intake of antioxidant vitamins and the incidence of
total stroke and ischemic stroke. SUBJECTS/METHODS: The subjects were 82 044
Japanese men and women aged 45-74 years under the Japan Public Health Center
based Prospective Cohort Study. Between 1995 and 1997, dietary assessment was
done using a food frequency questionnaire. During 983 857 person-years of follow
up until the end of 2009 we documented 3541 incident total strokes and 2138
ischemic strokes. RESULTS: Dietary intakes of alpha-carotene, beta-carotene,
alpha-tocopherol and vitamin C were not inversely associated with the incidence
of total stroke and ischemic stroke adjustment for cardiovascular risk factors
and selected lifestyle variables. When stratified by current smoking status, the
inverse association between dietary vitamin C intake and incidence of total
stroke observed among non-smokers but not smokers, with respective multivariable
hazard ratios for the highest versus lowest quintiles of vitamin C of 0.81 (95%
confidence interval (CI), 0.68-0.96; P-trend=0.03) among non-smokers; and 1.03
(0.84-1.25; P-trend=0.55) among smokers. As for ischemic stroke, the
corresponding multivariable hazard ratios were 0.76 (0.60-0.96; P-trend=0.02)
among non-smokers; and 1.00 (0.78-1.28; P-trend=0.61) among smokers. CONCLUSIONS:
Dietary vitamin C intake was inversely associated with the incidence of total
stroke and ischemic stroke among non-smokers.
PMID- 28699630
TI - Prevalence and clinical correlation of dysphagia in Parkinson disease: a study on
Chinese patients.
AB - BACKGROUND/OBJECTIVES: Dysphagia is relatively common in patients with Parkinson
disease (PD) and can have a negative impact on their quality of life; therefore,
it is imperative that its prevalence in PD patients is studied. The aim of this
study was to explore the prevalence and clinical correlation of dysphagia in
Chinese PD patients. SUBJECTS/METHODS: We recruited 116 Chinese PD patients. A
videofluoroscopic study of swallowing (VFSS) was used to identify dysphagia.
Assessments, including water drinking test, relative motor symptoms, non-motor
symptoms (NMS) and quality of life, were performed to analyze the risks of
dysphagia. RESULTS: The prevalence of dysphagia was 87.1%. The comparison of
demographic and clinical features between patients with and without dysphagia
included sex, education level, disease course, Mini-mental State Examination
(MMSE), Hamilton Depression Scale (HAMD), Hamilton Anxiety Scale (HAMA), Question
6, 7 of the Unified Parkinson Disease Rating Scale (UPDRS Part II), Hoehn-Yahr
stage (H&Y), water drinking test, 39-item Parkinson Disease Questionnaire (PDQ
39) and Non-Motor Symptoms Quest (NMSQ). We found significant correlations
between dysphagia and age. Using age, disease course, and H&Y stage as the
independent variable in our regression analysis for assessing the risk factors of
dysphagia in PD patients, age and H&Y stage displayed a strong correlation as the
risk factors. The risk of dysphagia in elderly PD patients is 1.078 times greater
than that of younger PD patients. Also, the risk of dysphagia in PD patients of a
greater H&Y staging is 3.260 times greater than that of lower staging PD
patients. CONCLUSIONS: Our results suggest that dysphagia is common in Chinese PD
patients. Older patients or those in higher H&Y stages are more likely to
experience dysphagia. There is no correlation between dysphagia and PD duration.
PMID- 28699631
TI - Co-inheritance of mutations associated with arrhythmogenic cardiomyopathy and
hypertrophic cardiomyopathy.
AB - Arrhythmogenic cardiomyopathy (ACM) and hypertrophic cardiomyopathy (HCM) are
genetically and phenotypically distinct disorders of the myocardium. Here we
describe for the first time co-inheritance of mutations in genes associated with
ACM or HCM in two families with recurrence of both cardiomyopathies. Among the
double heterozygotes for mutations in desmoplakin (DSP) and myosin binding
protein C (MYBPC3) genes identified in Family A, two were diagnosed with ACM and
two with HCM. In Family B, one patient was identified to carry mutations in alpha
T-catenin (CTTNA3) and beta-myosin (MYH7) genes, but he does not fulfill the
current diagnostic criteria neither for ACM nor for HCM. Interestingly, the
double heterozygotes showed a variable clinical expression of both
cardiomyopathies and they do not exhibit a more severe phenotype than family
members carrying only one of the two mutations.
PMID- 28699632
TI - Wilms tumour in Beckwith-Wiedemann Syndrome and loss of methylation at imprinting
centre 2: revisiting tumour surveillance guidelines.
AB - Beckwith-Wiedemann Syndrome (BWS) is an overgrowth syndrome caused by a variety
of molecular changes on chromosome 11p15.5. Children with BWS have a significant
risk of developing Wilms tumours with the degree of risk being dependent on the
underlying molecular mechanism. In particular, only a relatively small number of
children with loss of methylation at the centromeric imprinting centre (IC2) were
reported to have developed Wilms tumour. Discontinuation of tumour surveillance
for children with BWS and loss of methylation at IC2 has been proposed in several
recent publications. We report here three children with BWS reported to have loss
of methylation at IC2 on clinical testing who developed Wilms tumour or precursor
lesions. Using multiple molecular approaches and multiple tissues, we
reclassified one of these cases to paternal uniparental disomy for chromosome
11p15.5. These cases highlight the current challenges in definitively assigning
tumour risk based on molecular classification in BWS. The confirmed cases of loss
of methylation at IC2 also suggest that the risk of Wilms tumour in this
population is not as low as previously thought. Therefore, we recommend that for
now, all children with a clinical or molecular diagnosis of BWS be screened for
Wilms tumour by abdominal ultrasonography until the age of eight years regardless
of the molecular classification.
PMID- 28699633
TI - Reversal of cancer gene expression correlates with drug efficacy and reveals
therapeutic targets.
AB - The decreasing cost of genomic technologies has enabled the molecular
characterization of large-scale clinical disease samples and of molecular changes
upon drug treatment in various disease models. Exploring methods to relate
diseases to potentially efficacious drugs through various molecular features is
critically important in the discovery of new therapeutics. Here we show that the
potency of a drug to reverse cancer-associated gene expression changes positively
correlates with that drug's efficacy in preclinical models of breast, liver and
colon cancers. Using a systems-based approach, we predict four compounds showing
high potency to reverse gene expression in liver cancer and validate that all
four compounds are effective in five liver cancer cell lines. The in vivo
efficacy of pyrvinium pamoate is further confirmed in a subcutaneous xenograft
model. In conclusion, this systems-based approach may be complementary to the
traditional target-based approach in connecting diseases to potentially
efficacious drugs.
PMID- 28699634
TI - Scalable variable-index elasto-optic metamaterials for macroscopic optical
components and devices.
AB - Optical metamaterials with an artificial subwavelength structure offer new
approaches to implement advanced optical devices. However, some of the biggest
challenges associated with the development of metamaterials in the visible
spectrum are the high costs and slow production speeds of the nanofabrication
processes. Here, we demonstrate a macroscale (>35 mm) transformation-optics wave
bender (293 mm2) and Luneburg lens (855 mm2) in the broadband white-light visible
wavelength range using the concept of elasto-optic metamaterials that combines
optics and solid mechanics. Our metamaterials consist of mesoscopically
homogeneous chunks of bulk aerogels with superior, broadband optical transparency
across the visible spectrum and an adjustable, stress-tuneable refractive index
ranging from 1.43 down to nearly the free space index (~1.074). The experimental
results show that broadband light can be controlled and redirected in a volume of
>105lambda * 105lambda * 103lambda, which enables natural light to be processed
directly by metamaterial-based optical devices without any additional coupling
components.
PMID- 28699635
TI - Anion-capped metallohost allows extremely slow guest uptake and on-demand
acceleration of guest exchange.
AB - The switching of molecular recognition selectivity is important for tuning
molecular functions based on host-guest binding. While the switching processes in
artificial functional molecules are usually driven by changes of the
thermodynamic stabilities, non-equilibrium phenomena also play an important role
in biological systems. Thus, here we designed a host-guest system utilizing a non
equilibrium kinetically trapped state for on-demand and time-programmable control
of molecular functions. We synthesized a bis(saloph) macrocyclic cobalt(III)
metallohost 1(OTf)2, which has anion caps at both sides of the cation-binding
site. The anion caps effectively retard the guest uptake/release so that we can
easily make a non-equilibrium kinetically trapped state. Indeed, we can obtain a
long-lived kinetically trapped state {[1.K]3++La3+} prior to the formation of the
thermodynamically more stable state {[1.La]5++K+}. The guest exchange to the more
stable state from this kinetically trapped state is significantly accelerated by
exchange of TfO- anion caps by AcO- in an on-demand manner.
PMID- 28699636
TI - Idiosyncratic Mojiang virus attachment glycoprotein directs a host-cell entry
pathway distinct from genetically related henipaviruses.
AB - In 2012, cases of lethal pneumonia among Chinese miners prompted the isolation of
a rat-borne henipavirus (HNV), Mojiang virus (MojV). Although MojV is genetically
related to highly pathogenic bat-borne henipaviruses, the absence of a conserved
ephrin receptor-binding motif in the MojV attachment glycoprotein (MojV-G)
indicates a differing host-cell recognition mechanism. Here we find that MojV-G
displays a six-bladed beta-propeller fold bearing limited similarity to known
paramyxoviral attachment glycoproteins, in particular at host receptor-binding
surfaces. We confirm the inability of MojV-G to interact with known paramyxoviral
receptors in vitro, indicating an independence from well-characterized
ephrinB2/B3, sialic acid and CD150-mediated entry pathways. Furthermore, we find
that MojV-G is antigenically distinct, indicating that MojV would less likely be
detected in existing large-scale serological screening studies focused on well
established HNVs. Altogether, these data indicate a unique host-cell entry
pathway for this emerging and potentially pathogenic HNV.
PMID- 28699637
TI - The entangled triplet pair state in acene and heteroacene materials.
AB - Entanglement of states is one of the most surprising and counter-intuitive
consequences of quantum mechanics, with potent applications in cryptography and
computing. In organic materials, one particularly significant manifestation is
the spin-entangled triplet-pair state, which mediates the spin-conserving fission
of one spin-0 singlet exciton into two spin-1 triplet excitons. Despite long
theoretical and experimental exploration, the nature of the triplet-pair state
and inter-triplet interactions have proved elusive. Here we use a range of
organic semiconductors that undergo singlet exciton fission to reveal the
photophysical properties of entangled triplet-pair states. We find that the
triplet pair is bound with respect to free triplets with an energy that is
largely material independent (~30 meV). During its lifetime, the component
triplets behave cooperatively as a singlet and emit light through a Herzberg
Teller-type mechanism, resulting in vibronically structured photoluminescence. In
photovoltaic blends, charge transfer can occur from the bound triplet pairs with
>100% photon-to-charge conversion efficiency.
PMID- 28699638
TI - BCAT1 controls metabolic reprogramming in activated human macrophages and is
associated with inflammatory diseases.
AB - Branched-chain aminotransferases (BCAT) are enzymes that initiate the catabolism
of branched-chain amino acids (BCAA), such as leucine, thereby providing
macromolecule precursors; however, the function of BCATs in macrophages is
unknown. Here we show that BCAT1 is the predominant BCAT isoform in human primary
macrophages. We identify ERG240 as a leucine analogue that blocks BCAT1 activity.
Selective inhibition of BCAT1 activity results in decreased oxygen consumption
and glycolysis. This decrease is associated with reduced IRG1 levels and
itaconate synthesis, suggesting involvement of BCAA catabolism through the
IRG1/itaconate axis within the tricarboxylic acid cycle in activated macrophages.
ERG240 suppresses production of IRG1 and itaconate in mice and contributes to a
less proinflammatory transcriptome signature. Oral administration of ERG240
reduces the severity of collagen-induced arthritis in mice and crescentic
glomerulonephritis in rats, in part by decreasing macrophage infiltration. These
results establish a regulatory role for BCAT1 in macrophage function with
therapeutic implications for inflammatory conditions.
PMID- 28699639
TI - Loss of mTORC1 signalling impairs beta-cell homeostasis and insulin processing.
AB - Deregulation of mTOR complex 1 (mTORC1) signalling increases the risk for
metabolic diseases, including type 2 diabetes. Here we show that beta-cell
specific loss of mTORC1 causes diabetes and beta-cell failure due to defects in
proliferation, autophagy, apoptosis and insulin secretion by using mice with
conditional (betaraKO) and inducible (MIP-betaraKOf/f) raptor deletion. Through
genetic reconstitution of mTORC1 downstream targets, we identify mTORC1/S6K
pathway as the mechanism by which mTORC1 regulates beta-cell apoptosis, size and
autophagy, whereas mTORC1/4E-BP2-eIF4E pathway regulates beta-cell proliferation.
Restoration of both pathways partially recovers beta-cell mass and
hyperglycaemia. This study also demonstrates a central role of mTORC1 in
controlling insulin processing by regulating cap-dependent translation of
carboxypeptidase E in a 4EBP2/eIF4E-dependent manner. Rapamycin treatment
decreases CPE expression and insulin secretion in mice and human islets. We
suggest an important role of mTORC1 in beta-cells and identify downstream
pathways driving beta-cell mass, function and insulin processing.
PMID- 28699640
TI - LFA-1 activates focal adhesion kinases FAK1/PYK2 to generate LAT-GRB2-SKAP1
complexes that terminate T-cell conjugate formation.
AB - Lymphocyte function-associated antigen 1 (LFA-1) affinity and avidity changes
have been assumed to mediate adhesion to intercellular adhesion molecule-1 for T
cell conjugation to dendritic cells (DC). Although the T-cell receptor (TCR) and
LFA-1 can generate intracellular signals, the immune cell adaptor protein linker
for the activation of T cells (LAT) couples the TCR to downstream events. Here,
we show that LFA-1 can mediate both adhesion and de-adhesion, dependent on
receptor clustering. Although increased affinity mediates adhesion, LFA-1 cross
linking induced the association and activation of the protein-tyrosine kinases
FAK1/PYK1 that phosphorylated LAT selectively on a single Y-171 site for the
binding to adaptor complex GRB-2-SKAP1. LAT-GRB2-SKAP1 complexes were distinct
from canonical LAT-GADs-SLP-76 complexes. LFA-1 cross-linking increased the
presence of LAT-GRB2-SKAP1 complexes relative to LAT-GADs-SLP-76 complexes. LFA-1
FAK1 decreased T-cell-dendritic cell (DC) dwell times dependent on LAT-Y171,
leading to reduced DO11.10 T cell binding to DCs and proliferation to OVA
peptide. Overall, our findings outline a new model for LFA-1 in which the
integrin can mediate both adhesion and de-adhesion events dependent on receptor
cross-linking.
PMID- 28699642
TI - Estrogen and progesterone receptor-positive bilateral nipple leiomyoma in a man.
PMID- 28699641
TI - Nilotinib dose-optimization in newly diagnosed chronic myeloid leukaemia in
chronic phase: final results from ENESTxtnd.
AB - The Evaluating Nilotinib Efficacy and Safety in Clinical Trials-Extending
Molecular Responses (ENESTxtnd) study was conducted to evaluate the kinetics of
molecular response to nilotinib in patients with newly diagnosed chronic myeloid
leukaemia in chronic phase and the impact of novel dose-optimization strategies
on patient outcomes. The ENESTxtnd protocol allowed nilotinib dose escalation
(from 300 to 400 mg twice daily) in the case of suboptimal response or treatment
failure as well as dose re-escalation for patients with nilotinib dose reductions
due to adverse events. Among 421 patients enrolled in ENESTxtnd, 70.8% (95%
confidence interval, 66.2-75.1%) achieved major molecular response (BCR-ABL1 <=
0.1% on the International Scale) by 12 months (primary endpoint). By 24 months,
81.0% of patients achieved major molecular response, including 63.6% (56 of 88)
of those with dose escalations for lack of efficacy and 74.3% (55 of 74) of those
with dose reductions due to adverse events (including 43 of 54 patients with
successful re-escalation). The safety profile of nilotinib was consistent with
prior studies. The most common non-haematological adverse events were headache,
rash, and nausea; cardiovascular events were reported in 4.5% of patients (grade
3/4, 3.1%). The study was registered at clinicaltrials.gov (NCT01254188).
PMID- 28699643
TI - NOTCH1 mutational status in chronic lymphocytic leukaemia: clinical relevance of
subclonal mutations and mutation types.
PMID- 28699644
TI - Roles of APOL1 G1 and G2 variants in sickle cell disease patients: kidney is the
main target.
AB - In African-American patients with sickle cell disease (SCD), APOL1 G1 and G2
variants are associated with increased risk of sickle cell nephropathy (SCN). To
determine the role of APOL1 variants in SCD patients living in Europe, we
genotyped 152 SCD patients [aged 30.4 (24.3-36.4) years], mainly of Sub-Saharan
African ancestry, for APOL1 G1 and G2 and for variants of four genes with kidney
tropism (GSTM1, GSTT1, GSTP1, and HMOX1). Homozygous or double-heterozygous APOL
G1 and G2 genotypes were strongly associated with end stage renal disease (P =
0.003) and worse Kidney Disease: Improving Global Outcomes stages (P = 0.001).
Further, these genotypes were associated in an age-dependent manner with lower
estimated glomerular filtration rate (eGFR, P = 0.008), proteinuria (P = 0.009)
and albuminuria (P < 0.001) but not with other SCD complications. Compared to
APOL1 G1/wild type (WT), the APOL1 G2/WT genotype was associated with a lower
eGFR (P = 0.04) in an age-dependent manner, suggesting that the G2/WT patients
are likely to have worse kidney prognosis. Other genes variants analysed were not
associated with SCN or other SCD complications. Our data indicate that APOL1
screening should be considered for the management of SCD patients, including
those of non-African-American origin, as those with homozygous or double
heterozygous variants are clearly at higher risk of SCN.
PMID- 28699645
TI - A proposed treatment algorithm for adults with Haemoglobin SC disease.
PMID- 28699646
TI - Review of Opioid Pharmacogenetics and Considerations for Pain Management.
AB - Opioid analgesics are the standards of care for the treatment of moderate to
severe nociceptive pain, particularly in the setting of cancer and surgery. Their
analgesic properties mainly emanate from stimulation of the MU receptors, which
are encoded by the OPRM1 gene. Hepatic metabolism represents the major route of
elimination, which, for some opioids, namely codeine and tramadol, is necessary
for their bioactivation into more potent analgesics. The highly polymorphic
nature of the genes coding for phase I and phase II enzymes (pharmacokinetics
genes) that are involved in the metabolism and bioactivation of opioids suggests
a potential interindividual variation in their disposition and, most likely,
response. In fact, such an association has been substantiated in several
pharmacokinetic studies described in this review, in which drug exposure and/or
metabolism differed significantly based on the presence of polymorphisms in these
pharmacokinetics genes. Furthermore, in some studies, the observed variability in
drug exposure translated into differences in the incidence of opioid-related
adverse effects, particularly nausea, vomiting, constipation, and respiratory
depression. Although the influence of polymorphisms in pharmacokinetics genes, as
well as pharmacodynamics genes (OPRM1 and COMT) on response to opioids has been a
subject of intense research, the results have been somehow conflicting, with some
evidence insinuating for a potential role for OPRM1. The Clinical
Pharmacogenetics Implementation Consortium guidelines provide CYP2D6-guided
therapeutic recommendations to individualize treatment with tramadol and codeine.
However, implementation guidelines for other opioids, which are more commonly
used in real-world settings for pain management, are currently lacking. Hence,
further studies are warranted to bridge this gap in our knowledge base and
ultimately ascertain the role of pharmacogenetic markers as predictors of
response to opioid analgesics.
PMID- 28699647
TI - Management of pregnancy in type 3 von Willebrand disease with alloantibodies.
PMID- 28699648
TI - MRC's proposal to change the submission procedure for the future submission of
assignment papers.
PMID- 28699649
TI - What is the evidence to support the use of plasma exchange as first-line therapy
for N-methyl d-aspartate receptor antibody encephalitis?
PMID- 28699651
TI - Combination of thresholding and fitting methods for measuring nanoparticle sizes
and size distributions in (S)TEM.
AB - The practical need for a simple and reliable tool for routine size analysis of
nanoparticles with diameters down to a few nm embedded in a polymer matrix
motivated the development of a new approach. The idea underlying the method
proposed in this work is to combine intensity thresholding and contrast fitting
procedures in the same software for particle recognition and measurements of
sizes and size distributions of nanoparticles in transmission and scanning
transmission electron microscopy images. Particle recognition in images is
performed in an interactive process of manual setting the numerical threshold
level after image preprocessing. We show that fitting the calculated gray level
distribution to the real images is able to provide a maximum accuracy in
measurements of the particle diameters in contrast to thresholding approaches.
The fitting procedure is applied in the vicinity of nanoparticle images with the
mass-thickness, diffraction, and chemical contrast. The grayscale function
associated to the nanoparticle thickness is described using polynomial
gt=g0+g1t+g2t2+g3t3... with degree ? 2 and undetermined coefficients. The program
for particle detection and size measurement-Analyzer of Nanoparticles (AnNa)-has
been written and is described here. It was successfully tested on systems
containing Ag nanoparticles grown and stabilized in aqueous solutions of
different polymers for biomedical use and is available from the authors.
PMID- 28699650
TI - Elevation of serum lactate dehydrogenase in AL amyloidosis reflects tissue damage
and is an adverse prognostic marker in patients not eligible for stem cell
transplantation.
AB - The significance of serum lactate dehydrogenase (LDH) in light chain (AL)
amyloidosis has not been previously explored. We studied 1019 newly diagnosed
patients and correlated the elevation of LDH above the upper limit of normal
(ULN) with disease characteristics and outcome. Four hundred and nine patients
had an LDH above ULN, representing 40% of the study population. Patients with an
elevated LDH were older, were less likely to be male and had more extensive organ
involvement compared to patients with a normal LDH. Patients with high LDH had
greater cardiac and renal dysfunction. Elevated LDH was an independent prognostic
marker for overall survival and for death within 6 months of diagnosis, but this
was restricted to patients not eligible for stem cell transplant. Serum LDH may
act as a marker for organ damage and should be explored as a potential marker for
tissue healing and organ recovery.
PMID- 28699652
TI - IMP-6 Carbapenemase-Producing Enterobacteriaceae Bacteremia Successfully Treated
with Amikacin-Meropenem in Two Patients.
AB - Infections caused by carbapenemase-producing Enterobacteriaceae (CPE) are
becoming increasingly common worldwide. Although CPE infections can be fatal, few
reports in the literature have described effective and successful treatments for
infectious diseases caused by several types of IMP CPE, and, to our knowledge, no
reports have described the successful treatment of IMP-6 CPE infections. We
describe two patients who developed bacteremia caused by IMP-6 CPE after surgery
for cancer who were successfully treated with amikacin plus high-dose prolonged
infusion meropenem. Both patients were treated over a 2-week period using
amikacin 15 mg/kg at various intervals based on therapeutic drug monitoring and
meropenem 2000 mg infused over 3 hours every 12 hours. The dosages of amikacin
and meropenem were determined based on the creatinine clearance of each patient.
Both patients were cured of their bacteremia and did not experience any
antibiotic-related adverse effects. Based on the outcomes of these patients, it
appears that amikacin plus high-dose prolonged-infusion meropenem may be safe and
effective for the treatment of bacteremia caused by IMP-6 CPE.
PMID- 28699653
TI - Richter syndrome presenting as Sister Mary Joseph umbilical nodule.
PMID- 28699654
TI - Health promotion in specialist and community care: how a broadly applicable
health promotion intervention influences patient's sense of coherence.
AB - BACKGROUND: Chronic illness health interventions aim to strengthen individuals'
wellness resources, in addition to their ability to handle their condition. This
presupposes a partnership between patients and professionals and flexibility in
care organization. AIM: This study aims to investigate possible changes in
individuals' sense of coherence while living with long-term illness as they
engage in a broadly applicable health promotion intervention developed in
specialist care settings that was later implemented in the community care
context. METHOD: This study had a pre-postdesign. Sense of coherence was measured
using the SOC-29 questionnaire at baseline and within 14 days of programme
completion. The total baseline sample included 108 Norwegian adults (aged 21-89)
with chronic illness. Data were analysed using paired samples t-tests. RESULTS:
In both clinical sites, the total sample's mean SOC score changed positively from
the baseline to the follow-up 4 months later. This change was larger for the
participants in the community care context. Manageability increased significantly
for women. Significant positive changes in SOC score and the manageability
dimension were also identified among participants who had children. Similar
findings were found for those who were living with a partner, as well as for
public transfer payment recipients. CONCLUSION: The intervention contributed to a
positive change in participants' SOC while living with illness. The findings
revealed that the intervention is a flexible health promotion tool across age,
diagnostic categories and clinical sites. The community participants' SOC changed
the most, which indicates that the intervention is especially relevant in the
follow-up of persons living with long-term illness within the community. The
intervention contributes to a shift of perspectives in health care towards
strenght-based care and health within illness.
PMID- 28699656
TI - SO2 F2 -Mediated One-Pot Synthesis of Aryl Carboxylic Acids and Esters from
Phenols through a Pd-Catalyzed Insertion of Carbon Monoxide.
AB - A one-pot Pd-catalyzed carbonylation of phenols into their corresponding aryl
carboxylic acids and esters through the insertion of carbon monoxide has been
developed. This procedure offers a direct synthesis of aryl carboxylic acids and
esters from inexpensive and abundant starting materials (phenols, SO2 F2 and CO)
under mild conditions. This method tolerates a broad range of functional groups
and is also applicable for the modification of complicated natural products.
PMID- 28699657
TI - Validation of the modified Chinese Cancer Survivor's Unmet Needs (CaSUN-C) for
women with breast cancer.
AB - OBJECTIVE: The aims of the study were to modify the Cancer Survivor's Unmet Need
(CaSUN) Scale into a short form and then test its psychometric scale-specific
properties for breast cancer survivors in Taiwan. METHODS: Using convenience
sampling, recruited breast cancer survivors were separated into 2 samples (sample
1, n = 150, and sample 2, n = 162). First, we translated and modified the CaSUN
to ensure cultural adaptation. Second, we used statistical methods to eliminate
some items and conducted an exploratory factor analysis (EFA) using sample 1 to
explore the factor structure of the CaSUN-C. Finally, we conducted a confirmatory
factor analysis using sample 2 to confirm the structure suggested by the EFA and
tested the criterion validity and known-group validity of the CaSUN-C. RESULTS:
Twenty items within 4 factors (information, physical /psychological, medical
care, and communication needs) were identified for the CaSUN-C. Each factor had
acceptable internal consistency (Cronbach's Alpha = .61 to .82). The criterion
validity was supported by the significant correlations between the CaSUN-C scores
and scores on fear of recurrence and depression. Known-group comparisons revealed
that women who survived more than 60 months had fewer physical/psychological
needs than those less 60 months, which supported the validity of CaSUN-C.
CONCLUSION: The CaSUN-C demonstrated acceptable reliability and validity for
assessing unmet needs among breast cancer survivors in Taiwan. Using this simple
assessment to target the individual needs of these survivors can help healthcare
professionals provide personalized care efficiently.
PMID- 28699655
TI - Repair or destruction-an intimate liaison between ubiquitin ligases and molecular
chaperones in proteostasis.
AB - Cellular differentiation, developmental processes, and environmental factors
challenge the integrity of the proteome in every eukaryotic cell. The maintenance
of protein homeostasis, or proteostasis, involves folding and degradation of
damaged proteins, and is essential for cellular function, organismal growth, and
viability . Misfolded proteins that cannot be refolded by chaperone machineries
are degraded by specialized proteolytic systems. A major degradation pathway
regulating cellular proteostasis is the ubiquitin (Ub)/proteasome system (UPS),
which regulates turnover of damaged proteins that accumulate upon stress and
during aging. Despite a large number of structurally unrelated substrates, Ub
conjugation is remarkably selective. Substrate selectivity is mainly provided by
the group of E3 enzymes. Several observations indicate that numerous E3 Ub
ligases intimately collaborate with molecular chaperones to maintain the cellular
proteome. In this review, we provide an overview of specialized quality control
E3 ligases playing a critical role in the degradation of damaged proteins. The
process of substrate recognition and turnover, the type of chaperones they team
up with, and the potential pathogeneses associated with their malfunction will be
further discussed.
PMID- 28699658
TI - Telomere length and somatic mutations in correlation with response to
immunosuppressive treatment in aplastic anaemia.
AB - We investigated the frequencies of cytogenetic aberrations and somatic mutations
of prognostic relevance in 393 patients with aplastic anaemia (AA). Clonality was
determined by G-banding/fluorescence in situ hybridization (FISH) (n = 245), and
targeted capture sequencing was performed for 88 haematopoiesis-related genes (n
= 70). The telomere length (TL) of bone marrow nucleated cells was measured at
the single cell level by FISH (n = 135). Eighteen (4.6%) patients showed disease
progression, and monosomy 7 (50.0%) was the most predominant cytogenetic
evolution at disease transformation. One third of patients (32.9%) presented at
least 1 mutation; the most frequently mutated genes were NOTCH1, NF1, SCRIB, BCOR
and DNMT3A. The patient group with clonal changes (30.7%) showed an adverse
response to immunosuppressive treatment (IST), compared to the non-clonal group,
but this finding did not show statistical significance. The TL of AA patients was
significantly shorter than normal control and patients with clonal changes showed
significantly shorter TLs. Patients with TL>5.9 showed a higher response rate to
IST (P = 0.048). In conclusion, the patients with clonal changes or TL attrition
showed a poor response to IST. Shorter TL can be used not only as a biomarker,
but also as a predictive marker for treatment response to IST.
PMID- 28699659
TI - Scanning electron and light microscopy of foliar epidermal characters: A tool for
plant taxonomists in the identification of grasses.
AB - SEM and light microscopy are of special interest for biologist to observe various
features of the living bodies. In the current study we observed the foliar
epidermal micro-morphological characters of 44 grass species using SEM and Light
microscopy to assess their taxonomic utility for taxonomists in the
identification process. The aim of this study is to use the foliar epidermal
structural variations in both upper and lower surfaces for identification of
grasses. Significant diversity was observed in both qualitative and quantitative
characters using SEM and Light microscopy. Variations were observed in stomatal
number, size, guard cells shape, silica bodies, macro-hairs, micro-hairs,
epidermal cell number, subsidiary cells, prickles, hooks, papillae, and short and
long cells. A taxonomic key is prepared using these variations for the
identification of grass species. Based on these findings, SEM and Light
microscopy of foliar epidermal features can be of special interest for
taxonomists in the identification of complex grass taxa.
PMID- 28699660
TI - Binding of indocyanine green in polycaprolactone fibers using blend
electrospinning for in vivo laser-assisted vascular anastomosis.
AB - BACKGROUND AND OBJECTIVE: The clinical application of laser-assisted vascular
anastomosis is afflicted by unreliable and low bonding strengths as well as
tedious handling during microvascular surgery. The challenge to be met arises
from the flow-off of the chromophore during soldering that changes the absorption
and stains the surrounding tissue, leading to an uncontrollable thermal damage
zone. In this study, we investigated the feasibility to produce an indocyanine
green (ICG)-loaded patch by electrospinning and tested its applicability to both
in vitro and in vivo microvascular laser soldering. MATERIALS AND METHODS: A
blend of polycaprolactone and ICG was electrospun to produce a pliable patch.
Prior to soldering, the patch was soaked in 40% wt. bovine serum albumin
solution. The solder patch was wrapped in vitro around blood vessel stumps of
rabbit aortas. An intraluminal balloon catheter enabled an easy alignment and
held the setup in place. The soldering energy was delivered via a diffusor fiber
from the vessel lumen using a diode laser at 810 nm. During the procedure, the
surface temperature was observed with an infrared camera. Afterward, samples were
embedded in methylmethacrylate and epon to study thermal damage. The quality of
the fusion was assessed by measuring the tensile strength. After in vitro tests
with rabbit aortas, eight large white pigs were subjected to an acute in vivo
experiment, and the artery of the latissimus dorsi flap was anastomosed to the
distal femoral artery. RESULTS: The ICG-loaded patch, produced by
electrospinning, has a thickness of 279 +/- 62 MUm, a fiber diameter of 1.20 +/-
0.19 MUm, and an attenuation coefficient of 1,119 +/- 183 cm-1 at a wavelength of
790 nm. The patch was pliable and easy to handle during surgery. No leakage of
the chromophore was observed. Thermal damage was restricted to the Tunica
adventitia and Tunica media and the area of the vessel wall that was covered with
the patch. Six pigs were successfully treated, without any bleeding and with a
continuous blood flow. The in vivo flap model yielded a similar tensile strength
compared to in vitro laser-assisted vascular anastomoses (138 +/- 52 vs. 117 +/-
30 mN/mm2 ). CONCLUSION: Our study demonstrated the applicability of the ICG
loaded patch for laser-assisted vascular anastomosis. By using electrospinning,
ICG could be bound to polymer fibers, avoiding its flow-off and the staining of
the surrounding tissue. This patch demonstrated several advantages over liquid
solder as it was easier to apply, ensured a high and reliable bonding strength
while maintaining a constant concentration of ICG concentration during the
surgery. Lasers Surg. Med. 49:928-939, 2017. (c) 2017 Wiley Periodicals, Inc.
PMID- 28699661
TI - Very early hallucinatory experiences: a school-based study.
AB - BACKGROUND: The prevalence and clinical significance of hallucinatory experiences
among children below 7 years of age remain unknown. We aimed to determine the
independent influences of sensory deficits, the presence of an imaginary
companion and metacognition on hallucinatory experiences. We assumed that
hallucinatory experiences were associated with (a) sensory deficits, (b) the
presence of an imaginary companion (IC) and (c) metacognition defaults (i.e.
first- and second-order theory of mind default). METHODS: All children in the
third year of preschool from a region of Northern France underwent medical
screening. We compared the prevalence rates of visual, auditory and audio-visual
hallucinatory experiences based on (a) the presence of visual or auditory
deficits, (b) the actual presence of an IC and (c) metacognition. The analyses
were adjusted for age. RESULTS: A total of 1,087 children aged between 5 and 7
years were included. The prevalence rates of auditory, visual and audio-visual
hallucinatory experiences were 15.8%, 12.5% and 5.8%, respectively. The
prevalences of different types of hallucinatory experiences were not
significantly different according to sensory deficit. The prevalences of all
types of hallucinatory experiences were significantly higher among children with
an IC and among children with metacognition defaults. CONCLUSIONS: The
association between hallucinatory experiences and sensory deficits might concern
only long-lasting deficits. The association with the presence of an IC confirms
experimental findings of the likelihood of perceiving words among meaningless
auditory stimuli. Relations between hallucinatory experiences and theory of mind
need to be addressed in longitudinal studies.
PMID- 28699662
TI - Effects of calycosin against high-fat diet-induced nonalcoholic fatty liver
disease in mice.
AB - BACKGROUND AND AIM: Nonalcoholic fatty liver disease (NAFLD) has become a major
health concern worldwide. The present study was designed to investigate the
effects of calycosin against high-fat diet (HFD)-induced NAFLD in mice. METHODS:
C57BL/6 J male mice were fed with HFD to induce NAFLD model and treated with or
without calycosin for 12 weeks. The levels of ALT, AST, insulin, and adiponectin
were measured using biochemical methods. Hemotoxylin and eosin staining and Oil
Red O staining were used to determine the liver histopathology changes and
measure the degree of lipid accumulation respectively. Glucose tolerance tests
and insulin tolerance tests were performed followed by quantitative insulin
sensitivity check index determination. Western blot and quantitative real-time
polymerase chain reaction were used to explore the potential mechanism involved
in the beneficial effects of calycosin. RESULTS: Calycosin effectively decreased
the levels of ALT and AST, increased the levels of adiponectin and insulin.
Hemotoxylin and eosin staining indicated calycosin treatment remarkably improved
liver injury. Oil Red O staining indicated calycosin treatment remarkably
improved lipid accumulation. Quantitative insulin sensitivity check index in HFD
fed mice was significantly lower than in the standard chow fed mice. Further,
calycosin suppressed phosphoenolpyruvate carboxykinase, glucose-6-phosphatase,
sterol-regulatory element binding protein 1c, and FASN involved in
gluconeogenesis and triglyceride synthesis. Calycosin increased glycogen synthase
kinase 3 beta, glucose transporter 4, and phosphorylated insulin receptor
substrates 1 and 2 expressions involved in glucose metabolism. The aforementioned
beneficial effects of calycosin against HFD-induced NAFLD may be attributed to
farnesoid X receptor activation. CONCLUSION: Calycosin could produce the
favorable effects against HFD-induced NAFLD in mice.
PMID- 28699664
TI - Erratum.
PMID- 28699663
TI - Posttraumatic Stress Symptoms and Alcohol-Related Outcomes Among Municipal
Firefighters.
AB - This study examined levels of posttraumatic stress symptoms (PTSS) and
relationships between PTSS and alcohol-related outcomes in a near census of
municipal firefighters. The study also assessed substance-use coping and drinking
to cope as potential mediators of such outcomes. Firefighters (N = 740) completed
measures that assessed PTSS, alcohol risk behaviors, alcohol problems, drinking
motives, and coping with stress. Results showed that 32.4% of firefighters
reported significant levels of PTSS using National Center for PTSD (2014)
screening cutoff scores. Correlational analysis showed that PTSS was related to
at-risk drinking (r = .18) and alcohol-related problems (r = .33), as well as use
of maladaptive coping strategies (r = .58) and substance use coping (r = .40).
Structural analyses comparing multiple alternative models suggested that a model
that included substance use coping and drinking to cope as mediators of the
association between PTSS and problem drinking provided the best fit to the data.
Tests of multigroup invariance confirmed this model. Overall, PTSS were common in
this population and they predicted maladaptive coping patterns and alcohol
related consequences. One implication of these findings is that fire departments
might consider adding or enhancing screening and treatment options for PTS,
alcohol misuse, or both.
PMID- 28699666
TI - Apoptosis inhibition of Atlantic salmon (Salmo salar) peritoneal macrophages by
Piscirickettsia salmonis.
AB - To improve the understanding of the piscirickettsiosis pathogenesis, the in vivo
apoptosis modulation of peritoneal macrophages and lymphocytes was studied in
juvenile Salmo salar intraperitoneally injected with Piscirickettsia salmonis.
Five fish were sampled at post-exposure days 1, 5, 8 (preclinical), 20 (clinical)
and 40 (post-clinical period of the disease), and the leucocytes of their
coelomic washings were analysed by flow cytometry (using the JC-1 cationic dye),
TUNEL and cytology to detect apoptotic cells. A selective and temporal pattern of
apoptosis modulation by P. salmonis infection was observed. Apoptosis in
lymphocytes was not affected, whereas it was inhibited in macrophages but only
during the preclinical stage of the induced piscirickettsiosis. Hence, it is
postulated that P. salmonis inhibits macrophage apoptosis at the beginning of the
disease development to survive, multiply and probably be transported inside these
phagocytes; once this process is complete, macrophage apoptosis is no longer
inhibited, thus facilitating the exit of the bacteria from the infected cells for
continuing their life cycle.
PMID- 28699667
TI - Mantle cell lymphoma: 2017 update on diagnosis, risk-stratification, and clinical
management.
AB - DISEASE OVERVIEW: Mantle cell lymphoma (MCL) is a non-Hodgkin lymphoma
characterized by involvement of the lymph nodes, spleen, blood and bone marrow
with a short remission duration to standard therapies and a median overall
survival (OS) of 4-5 years. DIAGNOSIS: Diagnosis is based on lymph node, bone
marrow, or tissue morphology of centrocytic lymphocytes, small cell type, or
blastoid variant cells. A chromosomal translocation t (11:14) is the molecular
hallmark of MCL, resulting in the overexpression of cyclin D1. Cyclin D1 is
detected by immunohistochemistry in 98% of cases. The absence of SOX-11 or a low
Ki-67 may correlate with a more indolent form of MCL. The differential diagnosis
of MCL includes small lymphocytic lymphoma, marginal zone lymphoma, and
follicular lymphoma. RISK STRATIFICATION: The MCL International Prognostic Index
(MIPI) is the prognostic model most often used and incorporates ECOG performance
status, age, leukocyte count, and lactic dehydrogenase. A modification of the
MIPI also adds the Ki-67 proliferative index if available. The median OS for the
low-risk group was not reached (5-year OS of 60%). The median OS for the
intermediate risk group was 51 months and 29 months for the high risk group. RISK
ADAPTED THERAPY: For selected indolent, low MIPI MCL patients, initial
observation may be appropriate therapy. For younger patients with intermediate or
high risk MIPI MCL, aggressive therapy with a cytotoxic Regimen followed by
autologous stem cell transplantation should be considered. Rituximab maintenance
after autologous stem cell transplantation has also improved the progression-free
and overall survival. For older symptomatic MCL patients with intermediate or
high risk MIPI, combination chemotherapy with R-CHOP, R-Bendamustine, or a
clinical trial should be considered. In addition, rituximab maintenance therapy
may prolong the progression-free survival. At the time of relapse, agents
directed at activated pathways in MCL cells such as bortezomib (NFkB inhibitor),
lenalidamide (anti-angiogenesis) and Ibruitinib (Bruton's Tyrosine Kinase [BTK]
inhibitor) have demonstrated excellent clinical activity in MCL patients.
Autologous or allogeneic stem cell transplantation can also be considered in
young patients. Clinical trials with novel agents are always a consideration for
MCL patients.
PMID- 28699668
TI - POEMS syndrome: 2017 Update on diagnosis, risk stratification, and management.
AB - DISEASE OVERVIEW: POEMS syndrome is a paraneoplastic syndrome due to an
underlying plasma cell neoplasm. The major criteria for the syndrome are
polyradiculoneuropathy, clonal plasma cell disorder (PCD), sclerotic bone
lesions, elevated vascular endothelial growth factor, and the presence of
Castleman disease. Minor features include organomegaly, endocrinopathy,
characteristic skin changes, papilledema, extravascular volume overload, and
thrombocytosis. Diagnoses are often delayed because the syndrome is rare and can
be mistaken for other neurologic disorders, most commonly chronic inflammatory
demyelinating polyradiculoneuropathy. POEMS syndrome should be distinguished from
the Castleman disease variant of POEMS syndrome, which has no clonal PCD and
typically little to no peripheral neuropathy but has several of the minor
diagnostic criteria for POEMS syndrome. DIAGNOSIS: The diagnosis of POEMS
syndrome is made with 3 of the major criteria, two of which must include
polyradiculoneuropathy and clonal plasma cell disorder, and at least one of the
minor criteria. RISK STRATIFICATION: Because the pathogenesis of the syndrome is
not well understood, risk stratification is limited to clinical phenotype rather
than specific molecular markers. The number of clinical criteria is not
prognostic, but the extent of the plasma cell disorder is. Those patients with an
iliac crest bone marrow biopsy that does not reveal a plasma cell clone are
candidates for local radiation therapy; those with a more extensive or
disseminated clone will be candidates for systemic therapy RISK-ADAPTED THERAPY:
For those patients with a dominant sclerotic plasmacytoma, first-line therapy is
irradiation. Patients with diffuse sclerotic lesions or disseminated bone marrow
involvement and for those who have progression of their disease 3-6 months after
completing radiation therapy should receive systemic therapy. Corticosteroids are
temporizing, but alkylators are the mainstay of treatment, either in the form of
low-dose conventional therapy or high dose with stem cell transplantation.
Lenalidomide shows promise with manageable toxicity. Thalidomide and bortezomib
also have activity, but their benefit needs to be weighed against their risk of
exacerbating the peripheral neuropathy. The benefit of anti-VEGF antibodies is
conflicting. Prompt recognition and institution of both supportive care measures
and therapy directed against the plasma cell result in the best outcomes.
PMID- 28699669
TI - Detection of Mycobacterium marinum, M. peregrinum, M. fortuitum and M. abscessus
in aquarium fish.
PMID- 28699670
TI - Aminopyridine-Borane Complexes as Hydrogen Atom Donor Reagents: Reaction
Mechanism and Substrate Selectivity.
AB - Lewis base-borane complexes are shown to be potent hydrogen atom donors in
radical chain reduction reactions. Results obtained in 1 H, 11 B, and 13 C NMR
measurements and kinetic experiments support a complex reaction mechanism
involving the parent borane as well as its initial reaction products as active
hydrogen atom donors. Efficient reduction reactions of iodides, bromides, and
xanthates in apolar solvents rely on initiator systems generating oxygen-centered
radicals under thermal conditions and pyridine-borane complexes carrying
solubilizing substituents. In contrast to tin hydride reagents, the pyridine
boranes reduce xanthates faster than the corresponding iodides.
PMID- 28699671
TI - Primary myelofibrosis presenting in acute promyelocytic transformation.
PMID- 28699672
TI - Myelomonocytic differentiation associated with NPM1-RARA rearrangement.
PMID- 28699673
TI - Combined intravitreal methotrexate and immunochemotherapy followed by reduced
dose whole-brain radiotherapy for newly diagnosed B-cell primary intraocular
lymphoma.
AB - Primary intraocular lymphoma (IOL) has a propensity for central nervous system
(CNS) relapse within 2 years of initial diagnosis, affecting clinical outcome. To
reduce CNS relapse, we performed the combination treatment protocols of
intravitreal methotrexate injections, methotrexate-based systemic induction
chemotherapy and consolidation high-dose cytarabine and reduced-dose whole brain
radiation therapy (rdWBRT, 23.4 Gy) for B-cell primary IOL with or without newly
diagnosed CNS involvement. All patients underwent longitudinal brain magnetic
resonance imaging (MRI) and cognitive assessment for evaluation of treatment
induced leucoencephalopathy. Seventeen patients initiated and 16 completed the
protocol treatment. CNS relapse occurred in 2 patients and intraocular relapse in
3. Four-year progression-free survival (PFS) was 74.9% and 4-year overall
survival (OS) was 86.3%, with a median follow-up period of 48.9 months. Of 11
patients without CNS involvement, 1 had CNS relapse and 3 intraocular relapse,
and 4-year PFS and OS was 72.7% and 88.9%, respectively. Although white matter
abnormalities shown by MRI were significantly increased at 4 years after rdWBRT,
only one patient developed mild cognitive impairment. The combination of
intravitreal chemotherapy, prophylactic systemic chemotherapy and rdWBRT for
primary IOL showed a potential to reduce CNS relapse rate and improved 4-year PFS
and OS without increase of cognitive dysfunction.
PMID- 28699674
TI - Multiple myeloma with crystalline and Auer rod-like inclusions.
PMID- 28699675
TI - Intracranial haemorrhage in children and adolescents with severe haemophilia A or
B - the impact of prophylactic treatment.
AB - The discussion of prophylactic therapy in haemophilia is largely focused on joint
outcomes. The impact of prophylactic therapy on intracranial haemorrhage (ICH) is
less known. This study aimed to analyse ICH in children with haemophilia, with a
focus on different prophylaxis regimens and sequelae of ICH. We conducted a
multicentre retrospective and prospective study that included 33 haemophilia
centres from 20 countries. Inclusion criteria were children and adolescents born
between 1993 and 2014, with severe haemophilia A or B without inhibitors.
Participants were categorized by prophylaxis regimen: full, partial or none,
based on dose and dose frequency of regular infusions. The cohort study included
1515 children: 29 cases of ICH over 8038 patient years were reported. The
incidence of ICH in the prophylaxis group, 0.00033 cases of ICH/patient year, was
significantly lower compared to the no prophylaxis group, 0.017 cases of
ICH/patient year (RR 50.06; P < 0.001) and the partial prophylaxis group, 0.0050
cases of ICH/patient year (RR 14.92; P = 0.007). In the on-demand-group, 8%
(2/24) children with ICH died and 33% had long-term sequelae, including
intellectual and behavioural problems, paresis and epilepsy. Children on regular,
frequent prophylaxis have a low risk of ICH compared to those using non-frequent
or no prophylaxis.
PMID- 28699676
TI - Influence of multi-wavelength laser irradiation of enamel and dentin surfaces at
0.355, 2.94, and 9.4 MUm on surface morphology, permeability, and acid
resistance.
AB - OBJECTIVE: Ultraviolet (UV) and infrared (IR) lasers can be used to specifically
target protein, water, and mineral, respectively, in dental hard tissues to
produce varying changes in surface morphology, permeability, reflectivity, and
acid resistance. The purpose of this study was to explore the influence of laser
irradiation and topical fluoride application on the surface morphology,
permeability, reflectivity, and acid resistance of enamel and dentin to shed
light on the mechanism of interaction and develop more effective treatments.
METHODS: Twelve bovine enamel surfaces and twelve bovine dentin surfaces were
irradiated with various combinations of lasers operating at 0.355 (Freq.-tripled
Nd:YAG (UV) laser), 2.94 (Er:YAG laser), and 9.4 MUm (CO2 laser), and surfaces
were exposed to an acidulated phosphate fluoride gel and an acid challenge.
Changes in the surface morphology, acid resistance, and permeability were
measured using digital microscopy, polarized light microscopy, near-IR
reflectance, fluorescence, polarization sensitive-optical coherence tomography
(PS-OCT), and surface dehydration rate measurements. RESULTS: Different laser
treatments dramatically influenced the surface morphology and permeability of
both enamel and dentin. CO2 laser irradiation melted tooth surfaces. Er:YAG and
UV lasers, while not melting tooth surfaces, showed markedly different surface
roughness. Er:YAG irradiation led to significantly rougher enamel and dentin
surfaces and led to higher permeability. There were significant differences in
acid resistance among the various treatment groups. CONCLUSION: Surface
dehydration measurements showed significant changes in permeability after laser
treatments, application of fluoride and after exposure to demineralization. CO2
laser irradiation was most effective in inhibiting demineralization on enamel
while topical fluoride was most effective for dentin surfaces. Lasers Surg. Med.
49:913-927, 2017. (c) 2017 Wiley Periodicals, Inc.
PMID- 28699677
TI - Metformin ameliorates BSCB disruption by inhibiting neutrophil infiltration and
MMP-9 expression but not direct TJ proteins expression regulation.
AB - Blood-spinal cord barrier (BSCB) disruption is a major process for the secondary
injury of spinal cord injury (SCI) and is considered to be a therapeutic target
for SCI. Previously, we demonstrated that metformin could improve functional
recovery after SCI; however, the effect of metformin on BSCB is still unknown. In
this study, we found that metformin could prevent the loss of tight junction (TJ)
proteins at day 3 after SCI in vivo, but in vitro there was no significant
difference of these proteins between control and metformin treatment in
endothelial cells. This indicated that metformin-induced BSCB protection might
not be mediated by up-regulating TJ proteins directly, but by inhibiting TJ
proteins degradation. Thus, we investigated the role of metformin on MMP-9 and
neutrophils infiltration. Neutrophils infiltration is the major source of the
enhanced MMP-9 in SCI. Our results showed that metformin decreased MMP-9
production and blocked neutrophils infiltration at day 1 after injury, which
might be related to ICAM-1 down-regulation. Also, our in vitro study showed that
metformin inhibited TNF-alpha-induced MMP-9 up-regulation in neutrophils, which
might be mediated via an AMPK-dependent pathway. Together, it illustrated that
metformin prevented the breakdown of BSCB by inhibiting neutrophils infiltration
and MMP-9 production, but not by up-regulating TJ proteins expression. Our study
may help to better understand the working mechanism of metformin on SCI.
PMID- 28699678
TI - The effect of furcation involvement on tooth loss in a population without regular
periodontal therapy.
AB - AIM: We aimed to assess the association between furcation involvement (FI) and
tooth loss for subjects not undergoing regular periodontal treatment. MATERIALS
AND METHODS: Data from 2333 subjects participating in the baseline and 11-year
follow-up of the Study of Health in Pomerania (SHIP) were used. All subjects had
half-mouth periodontal examinations, including FI in one upper and one lower
molar, at baseline. A total of 1897 subjects and 3267 molars were included in the
final analysis. RESULTS: In total, 375 subjects (19.8%) lost molars during the
follow-up period. Respectively, 5.6%, 12.7%, 34.0% and 55.6% of molars without
FI, degree I FI, degree II FI and degree III FI were lost. Initial probing pocket
depth (PPD) and clinical attachment level (CAL) were associated with molar loss
(p < .001). Baseline degree I FI was associated with a 1.73 IRR (incidence rate
ratio) (95% CI=1.34-2.23, p < .001) of tooth loss while degree II-III was
associated with a 3.88 IRR (95% CI=2.94-5.11, p < .001) of tooth loss compared to
molars without FI at baseline. CONCLUSION: This study provides evidence for an
increased risk of molar loss affected by periodontal furcation involvement in a
general population not undergoing regular periodontal care.
PMID- 28699679
TI - One session of remote ischemic preconditioning does not improve vascular function
in acute normobaric and chronic hypobaric hypoxia.
AB - NEW FINDINGS: What is the central question of this study? It is suggested that
remote ischemic preconditioning (RIPC) might offer protection against ischaemia
reperfusion injuries, but the utility of RIPC in high-altitude settings remains
unclear. What is the main finding and its importance? We found that RIPC offers
no vascular protection relative to pulmonary artery pressure or peripheral
endothelial function during acute, normobaric hypoxia and at high altitude in
young, healthy adults. However, peripheral chemosensitivity was heightened 24 h
after RIPC at high altitude. Application of repeated short-duration bouts of
ischaemia to the limbs, termed remote ischemic preconditioning (RIPC), is a novel
technique that might have protective effects on vascular function during hypoxic
exposures. In separate parallel-design studies, at sea level (SL; n = 16) and
after 8-12 days at high altitude (HA; n = 12; White Mountain, 3800 m),
participants underwent either a sham protocol or one session of four bouts of 5
min of dual-thigh-cuff occlusion with 5 min recovery. Brachial artery flow
mediated dilatation (FMD; ultrasound), pulmonary artery systolic pressure (PASP;
echocardiography) and internal carotid artery (ICA) flow (ultrasound) were
measured at SL in normoxia and isocapnic hypoxia (end-tidal PO2 maintained at 50
mmHg) and during normal breathing at HA. The hypoxic ventilatory response (HVR)
was measured at each location. All measures at SL and HA were obtained at
baseline (BL) and at 1, 24 and 48 h post-RIPC or sham. At SL, RIPC produced no
changes in FMD, PASP, ICA flow, end-tidal gases or HVR in normoxia or hypoxia. At
HA, although HVR increased 24 h post-RIPC compared with BL [2.05 +/- 1.4 versus
3.21 +/- 1.2 l min-1 (% arterial O2 saturation)-1 , P < 0.01], there were no
significant differences in FMD, PASP, ICA flow and resting end-tidal gases.
Accordingly, a single session of RIPC is insufficient to evoke changes in
peripheral, pulmonary and cerebral vascular function in healthy adults. Although
chemosensitivity might increase after RIPC at HA, this did not confer any
vascular changes. The utility of a single RIPC session seems unremarkable during
acute and chronic hypoxia.
PMID- 28699680
TI - Intermacrocyclic Interaction Triggers Facile One-Pot Synthesis of a Chlorin
Porphyrin Heterodimer.
AB - This work reports a highly facile one-pot synthesis of a new series of fully pi
conjugated unsymmetric chlorin-porphyrin heterodimers with quantitative yields by
utilizing intermacrocyclic interactions. One-electron oxidations of dicopper(II)
and dipalladium(II) porphyrin dimers using mild oxidants such as iodine at room
temperature resulted in the formation of a strongly interacting cofacial mixed
valent pi-cation radical dimers. The radical, being highly reactive, drives
spontaneous and rapid transformation involving a new N=C bond formation, 1,2
ethyl migration, and the generation of a new indolizinium ring that bridges
between the two macrocycles. X-ray structural characterization of the
heterodimers reveals that the two macrocycles are nearly coplanar and thereby
extends the pi-conjugation from one end to the other. DFT calculations that
reproduce the experimental results are also reported.
PMID- 28699681
TI - Occurrence of signs of osteoarthritis/arthrosis in the temporomandibular joint on
panoramic radiographs in Swedish women.
AB - OBJECTIVES: To determine the prevalence and incidence of radiographic signs of
osteoarthritis/osteoarthrosis (OA) in the temporomandibular joint (TMJ) among
middle-aged and older women. METHODS: Data were collected from ongoing
representative, longitudinal and repeated cross-sectional studies in Gothenburg,
Sweden. Panoramic radiographs (PAN) have been taken regularly since 1968. The
cohorts were systematically selected from the female population at the ages of
38, 50, 62 and 74. Condylar alterations indicative of OA
(flattening/osteophyte/erosion) were evaluated in a total of 5234 PANs by one
examiner under standardized conditions. Intra-examiner reliability was good.
Sensitivity was poor, and specificity was acceptable in relation to computed
tomography. RESULTS: The prevalence of signs of OA in the TMJ was 18% on
panoramic radiographs at the age of 38, gradually increasing with age. At the age
of 62, the prevalence was 38%, and it was stable around 45% in the older age
groups. The highest incidence rate of OA was between the ages of 55 and 65.
Bilateral OA was uncommon. Flattening was the most prominent finding. CONCLUSION:
The prevalence of signs of OA in the TMJ, including remodeling, evaluated on
panoramic radiographs in representative cohorts of women, increases substantially
with age. Around one in every five middle-aged women and almost every second
woman of older ages can be expected to have some radiographic alteration in the
TMJ. The highest proportion with new findings of OA is to be found among older
middle-aged women.
PMID- 28699683
TI - Agreement between specific measures of adiposity and associations with high blood
pressure in black South African women.
AB - OBJECTIVES: To derive percentage body fat (%BF) cut-points according to body mass
index (BMI) categories for adult black South African women and to investigate the
agreement between adiposity classifications according to WHO BMI and %BF cut
points. The secondary aim was to determine the association between these
different adiposity measures and high blood pressure. METHODS: Black women aged
29-65 years (n = 435) from Ikageng, South Africa, were included in this cross
sectional study. Socio-demographic and anthropometric data were collected
(weight, height and BMI). %BF using dual-energy X-ray absorptiometry and blood
pressure were measured. RESULTS: There was significant agreement between three
%BF categories: low/normal (<35.8% age 29-49 years; or <38% age 50-65 years),
overweight range (35.8-40.7% age 29-49 years; or 38-42.1% age 50-65 years) and
obese (>=40.7% age 29-49 years; or >=42.1% age 50-65 years) and three BMI
categories: low/normal (<25 kg/m2 ), overweight range (25-29.9 kg/m2 ) and obese
(>=30kg/m2 ); (kappa = 0.62, P < .0001). Despite statistically significant
agreement between groups, more than half of overweight individuals were
misclassified as having either a normal (30.2%) or obese %BF (25.5%). %BF
misclassification was low in the low/normal and obese BMI ranges. After
adjustment for confounders, obesity (BMI >= 30kg/m2 ), as well as high %BF were
significantly associated with high blood pressure (OR = 1.75, 95% CI 1.09-2.81
versus OR = 1.92, 95% CI 1.15-3.23, respectively). CONCLUSION: Despite
significant agreement between BMI and %BF categories, considerable
misclassification occurred in the overweight range. Participants with excessive
%BF had a greater odds of high blood pressure than those in the highest BMI
category.
PMID- 28699682
TI - 2, 3, 7, 8-Tetrachlorodibenzo-p-dioxin promotes endothelial cell apoptosis
through activation of EP3/p38MAPK/Bcl-2 pathway.
AB - Endothelial injury or dysfunction is an early event in the pathogenesis of
atherosclerosis. Epidemiological and animal studies have shown that 2, 3, 7, 8
tetrachlorodibenzo-p-dioxin (TCDD) exposure increases morbidity and mortality
from chronic cardiovascular diseases, including atherosclerosis. However, whether
or how TCDD exposure causes endothelial injury or dysfunction remains largely
unknown. Cultured human umbilical vein endothelial cells (HUVECs) were exposed to
different doses of TCDD, and cell apoptosis was examined. We found that TCDD
treatment increased caspase 3 activity and apoptosis in HUVECs in a dose
dependent manner,at doses from 10 to 40 nM. TCDD increased cyclooxygenase enzymes
(COX)-2 expression and its downstream prostaglandin (PG) production (mainly PGE2
and 6-keto-PGF1alpha ) in HUVECs. Interestingly, inhibition of COX-2, but not COX
1, markedly attenuated TCDD-triggered apoptosis in HUVECs. Pharmacological
inhibition or gene silencing of the PGE2 receptor subtype 3 (EP3) suppressed the
augmented apoptosis in TCDD-treated HUVECs. Activation of the EP3 receptor
enhanced p38 MAPK phosphorylation and decreased Bcl-2 expression following TCDD
treatment. Both p38 MAPK suppression and Bcl-2 overexpression attenuated the
apoptosis in TCDD-treated HUVECs. TCDD increased EP3-dependent Rho activity and
subsequently promoted p38MAPK/Bcl-2 pathway-mediated apoptosis in HUVECs. In
addition, TCDD promoted apoptosis in vascular endothelium and delayed re
endothelialization after femoral artery injury in wild-type (WT) mice, but not in
EP3-/- mice. In summary, TCDD promotes endothelial apoptosis through the COX
2/PGE2 /EP3/p38MAPK/Bcl-2 pathway. Given the cardiovascular hazard of a COX-2
inhibitor, our findings indicate that the EP3 receptor and its downstream
pathways may be potential targets for prevention of TCDD-associated
cardiovascular diseases.
PMID- 28699684
TI - Laughter yoga activities for older people living in residential aged care homes:
A feasibility study.
AB - OBJECTIVE: To evaluate the effects of a laughter yoga activities (LY) program for
older people living in residential aged care homes (RACHs). METHODS: A 6-week LY
program was implemented at three RACHs with twenty-eight residents. A pre-post
design was used to measure positive and negative affect, happiness, blood
pressure and pulse. RESULTS: Post-session mean scores for positive mood, and
happiness were significantly higher than pre-session scores in weeks 1, 3 and 6,
and the post-session mean negative mood scores were significantly lower than pre
session scores in weeks 3 and 6. Post-session readings for mean systolic blood
pressure were significantly lower than pre-session readings in weeks 1 and 6.
CONCLUSION: This study demonstrates the potential for using LY to improve mood
and lower blood pressure of older people living in RACHs.
PMID- 28699685
TI - Pocket Pain and Neuromodulation: Negligible or Neglected?
AB - OBJECTIVES: Pain encountered at the site of the implantable pulse generator (IPG)
after invasive neuromodulation is a well-known and important complication. The
reported incidence of implant site pain is variable, ranging between 0.4 and 35%.
Implant site pain has never been systematically studied and no treatment
guidelines are available. MATERIAL AND METHODS: We performed an observational
study (study registration number mp05728) on the incidence and the determining
factors of implant site pain, the subjective rating of intensity by sending
questionnaires (n = 554) to our cohort of neuromodulation patients with IPGs. The
number of revision surgeries and explants due to implant site pain were also
analyzed. RESULTS: Total response rate was 50% (n = 278). Pain patients suffered
significantly (p < 0.05) more often from IPG site pain than other patients
undergoing neuromodulation therapies. Up to 64% of patients undergoing spinal
cord stimulation reported IPG site discomfort or pain. Severe pocket pain was
found in up to 8% of patients. No association was found between other variables
(age, BMI, duration of follow-up, gender, smoking, number of pocket surgeries)
and implant site pain. CONCLUSION: Pocket pain represents an important problem
after invasive neuromodulation and is more prevalent in pain patients. We believe
further technological improvements with miniaturized IPGs will impact the
incidence of pocket pain and could even obviate the need for an IPG pocket.
PMID- 28699686
TI - Ablation of ceramide synthase 2 exacerbates dextran sodium sulphate-induced
colitis in mice due to increased intestinal permeability.
AB - Ceramides mediate crucial cellular processes including cell death and
inflammation and have recently been implicated in inflammatory bowel disease.
Ceramides consist of a sphingoid long-chain base to which fatty acids of various
length can be attached. We now investigate the effect of alerting the ceramide
acyl chain length on a mouse model of colitis. Ceramide synthase (CerS) 2 null
mice, which lack very-long acyl chain ceramides with concomitant increase of long
chain bases and C16-ceramides, were more susceptible to dextran sodium sulphate
induced colitis, and their survival rate was markedly decreased compared with
that of wild-type littermates. Using mixed bone-marrow chimeric mice, we showed
that the host environment is primarily responsible for intestinal barrier
dysfunction and increased intestinal permeability. In the colon of CerS2 null
mice, the expression of junctional adhesion molecule-A was markedly decreased and
the phosphorylation of myosin light chain 2 was increased. In vitro experiments
using Caco-2 cells also confirmed an important role of CerS2 in maintaining
epithelial barrier function; CerS2-knockdown via CRISPR-Cas9 technology impaired
barrier function. In vivo myriocin administration, which normalized long-chain
bases and C16-ceramides of the colon of CerS2 null mice, increased intestinal
permeability as measured by serum FITC-dextran levels, indicating that altered
SLs including deficiency of very-long-chain ceramides are critical for epithelial
barrier function. In conclusion, deficiency of CerS2 influences intestinal
barrier function and the severity of experimental colitis and may represent a
potential mechanism for inflammatory bowel disease pathogenesis.
PMID- 28699687
TI - The super sickling haemoglobin HbS-Oman: a study of red cell sickling, K+
permeability and associations with disease severity in patients heterozygous for
HbA and HbS-Oman (HbA/S-Oman genotype).
AB - Studying different sickle cell genotypes may throw light on the pathogenesis of
sickle cell disease (SCD). Here, the clinical profile, red cell sickling and K+
permeability in 29 SCD patients (15 patients with severe disease and 14 with a
milder form) of HbA/S-Oman genotype were analysed. The super sickling nature of
this Hb variant was confirmed. The red cell membrane permeability to K+ was
markedly abnormal with elevated activities of Psickle , Gardos channel and KCl
cotransporter (KCC). Results were consistent with Ca2+ entry and Mg2+ loss via
Psickle stimulating Gardos channel and KCC activities. The abnormal red cell
behaviour was similar to that in the commonest genotype of SCD, HbSS, in which
the level of mutated Hb is considerably higher. Although activities of all three
K+ transporters also correlated with the level of HbS-Oman, there was no
association between transport phenotype and disease severity. The super sickling
behaviour of HbS-Oman may obviate the need for solute loss and red cell
dehydration to encourage Hb polymerisation, required in other SCD genotypes.
Disease severity was reduced by concurrent alpha thalassaemia, as observed in
other SCD genotypes, and represents an obvious genetic marker for prognostic
tests of severity in young SCD patients of the HbA/S-Oman genotype.
PMID- 28699688
TI - Photoionization and ionic dissociation of the C3 H3 NS molecule induced by soft X
ray near the C1s edge.
AB - Time of flight mass spectrometry, electron-ion coincidence, and ion yield
spectroscopy were employed to investigate for the first time the thiazole (C3 H3
NS) molecule in the gas phase excited by synchrotron radiation in the soft X-ray
domain. Total ion yield (TIY) and photoelectron-photoion coincidence (PEPICO)
spectra were recorded as a function of the photon energy in the vicinity of the
carbon K edge (C1s). The C1s resonant transitions as well as the core ionization
thresholds have been determined from the profile of TIY spectrum, and the
features were discussed. The corresponding partial ion yields were determined
from the PEPICO spectra for the cation species produced upon the molecular
photodissociation. Additional ab initio calculations have also been performed
from where relevant structural and electronic configuration parameters were
obtained for this molecule.
PMID- 28699689
TI - First report of Streptococcus parauberis in a cultured freshwater ornamental
fish, the ram cichlid Mikrogeophagus ramirezi (Myers & Harry, 1948).
PMID- 28699690
TI - microRNA let-7g suppresses PDGF-induced conversion of vascular smooth muscle cell
into the synthetic phenotype.
AB - Platelet-derived growth factor (PDGF) can promote vascular smooth muscle cells
(VSMCs) to switch from the quiescent contractile phenotype to synthetic
phenotype, which contributes to atherosclerosis. We aimed to investigate the role
of microRNA let-7g in phenotypic switching. Bioinformatics prediction was used to
find let-7g target genes in the PDGF/mitogen-activated protein kinase kinase
kinase 1 (MEKK1)/extracellular signal-regulated kinase (ERK)/Kruppel-like factor
4 (KLF4) signalling pathway that affects VSMC phenotypic switching. The
luciferase reporter assay and let-7g transfection were used to confirm let-7g
target genes. Two contractile proteins alpha-smooth muscle actin (alpha-SMA) and
calponin were VSMC-specific genes and were measured as the indicators for VSMC
phenotype. Lentivirus carrying the let-7g gene was injected to apolipoprotein E
knockout (apoE-/- ) mice to confirm let-7g's effect on preventing
atherosclerosis. Through the PDGF/MEKK1/ERK/KLF4 signalling pathway, PDGF-BB can
inhibit alpha-SMA and calponin. The PDGFB and MEKK1 genes were predicted to
harbour let-7g binding sites, which were confirmed by our reporter assays.
Transfection of let-7g to VSMC also reduced PDGFB and MEKK1 levels. Moreover, we
showed that let-7g decreased phosphorylated-ERK1/2 while had no effect on total
ERK1/2. KLF4 can reduce VSMC-specific gene expression by preventing myocardin
serum response factor (SRF) complex from associating with these gene promoters.
The immunoprecipitation assay showed that let-7g decreased the interaction
between KLF4 and SRF. Further experiments demonstrated that let-7g can increase
alpha-SMA and calponin levels to maintain VSMC in the contractile status.
Injection of lentivirus carrying let-7g gene increased let-7g's levels in aorta
and significantly decreased atherosclerotic plaques in the apoE-/- mice. We
demonstrated that let-7g reduces the PDGF/MEKK1/ERK/KLF4 signalling to maintain
VSMC in the contractile status, which further reduce VSMC atherosclerotic change.
PMID- 28699691
TI - Gold-Triggered Uncaging Chemistry in Living Systems.
AB - Recent advances in bioorthogonal catalysis are increasing the capacity of
researchers to manipulate the fate of molecules in complex biological systems. A
bioorthogonal uncaging strategy is presented, which is triggered by heterogeneous
gold catalysis and facilitates the activation of a structurally diverse range of
therapeutics in cancer cell culture. Furthermore, this solid-supported catalytic
system enabled locally controlled release of a fluorescent dye into the brain of
a zebrafish for the first time, offering a novel way to modulate the activity of
bioorthogonal reagents in the most fragile and complex organs.
PMID- 28699692
TI - Granulocyte-colony stimulating factor administration among hemoglobin S trait
donors: A single center experience from the Eastern Mediterranean region.
AB - BACKGROUND AND OBJECTIVE: Assessment of Hemoglobin S trait donors has gained
importance together with the increased allogeneic peripheral stem cell transplant
activity for sickle cell disease in the regions where the disease is prevalent.
Outcomes of Granulocyte-Colony Stimulating Factor (G-CSF) administration are
obscure for hemoglobin S trait donors. This study aims at investigating the
incidence of hemoglobin S carrier status and outcomes of G-CSF administration
among donors who live in Eastern Mediterranean region. MATERIAL AND METHOD: The
cross-sectional, single-center cohort study was performed with 147 donors between
January 2013 and March 2017. Prevalence of hemoglobin S trait was estimated and
subjects with or without Hemogobin S trait were compared with regard to stem cell
characteristics, early and late clinical outcomes after G-CSF administration.
RESULTS: Eleven out of 147 donors (7.48%) were found as hemoglobin S trait. G-CSF
administration was successfully completed and yielded good harvesting results in
hemoglobin S trait donors. No statistically significant difference was found
between groups with regard to early and late side effects, stem cell
characteristics. Blood pressures and QTc values were within normal ranges in both
groups. Groups were similar with regard to CD34 values. CONCLUSION: G-CSF seems
safe in hemoglobin S trait donors. Their being eligible as donors would increase
the chance of the patients for allogeneic stem cell transplantation in high
prevalence regions. Further studies are required to reveal the safety profile of
G-SCF in hemoglobin S carriers in different regions.
PMID- 28699693
TI - Isolation of Three Triterpene Saponins, Including Two New Oleanane Derivatives,
from Soldanella alpina and Hydrophilic Interaction Liquid Chromatography
Evaporative Light Scattering Detection of these Three Saponins in Four Soldenella
Species.
AB - INTRODUCTION: The genus Soldanella is one of the few endemic to Europe. Some of
its species have relevance in local traditional medicine. Earlier work has
indicated the possible presence of saponins in S. alpina. OBJECTIVE: To
investigate S. alpina and other related species for the occurrence of saponins.
METHODS: Following sequential extraction with n-hexane, dichloromethane and ethyl
acetate the subsequent methanolic extract of S. alpina roots was fractionated
after solvent precipitation using fast centrifugal partition chromatography and
column chromatography. Structures were elucidated by LC-MSn , high-resolution MS,
hydrolysis experiments and one-dimensional (1D)- and two-dimensional (2D)-NMR. A
hydrophilic interaction liquid chromatography method was developed to quantitate
saponins in the leaves and roots of four Soldanella species. RESULTS: Three
triterpene saponins, two of them new natural products, were isolated from S.
alpina. Based on an epoxyoleanal aglycone substituted with four sugar units, they
were analytically quantitated using a Kinetex 2.6 MUm hydrophilic interaction
liquid chromatography (HILIC) column together with a mobile phase comprising of
ammonium acetate, water and acetonitrile. Method validation confirmed that the
assay meets all requirements in respect to linearity, accuracy, sensitivity and
precision. All four Soldanella species investigated contained the three saponins.
The lowest total level of the three saponins (1.09%) was observed in S. montana
leaves while the highest saponin content (5.14%) was determined in S. alpina
roots. CONCLUSION: The detection of saponins within the genus Soldanella is an
indication that further phytochemical examination of this genus may reveal more
secondary metabolites of interest. Copyright (c) 2017 John Wiley & Sons, Ltd.
PMID- 28699695
TI - Mutual regulation between BCL6 and a specific set of miRNAs controls TFH
phenotype in peripheral T-cell lymphoma.
PMID- 28699694
TI - The epigenomics of schizophrenia, in the mouse.
AB - Large-scale consortia including the Psychiatric Genomics Consortium, the Common
Minds Consortium, BrainSeq and PsychENCODE, and many other studies taken together
provide increasingly detailed insights into the genetic and epigenetic risk
architectures of schizophrenia (SCZ) and offer vast amounts of molecular
information, but with largely unexplored therapeutic potential. Here we discuss
how epigenomic studies in human brain could guide animal work to test the impact
of disease-associated alterations in chromatin structure and function on
cognition and behavior. For example, transcription factors such as MYOCYTE
SPECIFIC ENHANCER FACTOR 2C (MEF2C), or multiple regulators of the open chromatin
mark, methyl-histone H3-lysine 4, are associated with the genetic risk
architectures of common psychiatric disease and alterations in chromatin
structure and function in diseased brain tissue. Importantly, these molecules
also affect cognition and behavior in genetically engineered mice, including
virus-mediated expression changes in prefrontal cortex (PFC) and other key nodes
in the circuitry underlying psychosis. Therefore, preclinical and small
laboratory animal work could target genomic sequences affected by chromatin
alterations in SCZ. To this end, in vivo editing of enhancer and other regulatory
non-coding DNA by RNA-guided nucleases including CRISPR-Cas, and designer
transcription factors, could be expected to deliver pipelines for novel
therapeutic approaches aimed at improving cognitive dysfunction and other core
symptoms of SCZ.
PMID- 28699696
TI - Scaling children's waist circumference for differences in body size.
AB - OBJECTIVES: Both waist circumference (WC) and body size (height) increase with
age throughout childhood. Hence, there is a need to scale WC in children to
detect differences in adiposity status (eg, between populations and different age
groups), independent of body size/height. METHODS: Using two culturally different
samples, 1 English (10-15.9 years n = 9471) and 2 Colombian (14-15 years, n =
37,948), for WC to be independent of height (HT), a body shape index was obtained
using the allometric power law WC = a.HTb . The model was linearized using log
transformation, and multiple regression/ANCOVA to estimate the height exponents
for WC controlling for age, sex, and any other categorical/population
differences. RESULTS: In both samples, the power-law height exponent varied
systematically with age. In younger children (age 10-11 years), the exponent was
approximately unity, suggesting that pre-pubertal children might be geometrically
similar. In older children, the height exponent declined monotonically to 0.5
(ie, HT0.5 ) in 15+ year-olds, similar to the exponent observed in adults. UK
children's height-adjusted WC revealed a "u" shaped curve with age that appeared
to reach a minimum at peak-height velocity, different for boys and girls.
Comparing the WC of two populations (UK versus Colombian 14-15-year-old children)
identified that the gap in WC between the countries narrowed considerably after
scaling for height. CONCLUSIONS: Scaling children's WC for differences in height
using allometric modeling reveals new insights into the growth and development of
children's WC, findings that might well have been be overlooked if body
size/height had been ignored.
PMID- 28699697
TI - The experiences of staff who support people with intellectual disability on
issues about death, dying and bereavement: A metasynthesis.
AB - BACKGROUND: Historically, people with intellectual disabilities have tended to be
excluded from knowing about death, dying and bereavement. Staff in intellectual
disability services can play a valuable role in improving understanding of these
issues in those they support. This qualitative metasynthesis aimed to understand
the experiences of staff supporting adults with intellectual disabilities with
issues of death, dying and bereavement. METHOD: Thirteen papers were identified
following a systematic review of six databases. RESULTS: Three themes were
developed following a lines-of-argument synthesis: (i) talking about death is
hard: negotiating the uncertainty in death, dying and bereavement; (ii) the
commitment to promoting a "good death"; and (iii) the grief behind the
professional mask. "A cautious silence: The taboo of death" was an overarching
theme. CONCLUSIONS: A more open culture around issues of death, dying and
bereavement in intellectual disability settings is essential and could be
promoted through staff training and support.
PMID- 28699698
TI - Reduced dosing and liability in methadone maintenance treatment by targeting
oestrogen signal for morphine addiction.
AB - Methadone maintenance treatment (MMT) is the major tapering therapy for morphine
addictive patients. There have gender differences reported in response to MMT.
This study discovered that the estrogen-response element single nucleotide
polymorphism (ERE-SNP; rs16974799, C/T) of cytochrome 2B6 gene (cyp2b6; methadone
catabolic enzyme) responded differently to MMT dosing. Oestradiol was associated
with high MMT dosing, high enantiomer (R- or S-) of 2-ethylidene-1,5-dimethyl-3,3
dipheny-pyrrolidine (EDDP; methadone metabolite) to methadone ratio and increased
drug-seeking behaviour, implicating oestradiol-CYP-EDDP/methadone axis decreasing
MMT efficacy. In mouse model, oestrogen mitigates methadone antinociceptive
response, facilitates methadone catabolism and up-regulates methadone-associated
metabolizing enzymes. Oestrogen also ablates chronic methadone administration
induced rewarding response. Mechanism dissection revealed the CC genotype of
CYP2B6-ERE-SNP exerts higher ERE sequence alignment score, higher estrogenic
response as compared to TT genotype. At last, preclinical study via targeting
estrogen signal that tamoxifen (TMX; selective estrogen receptor modulator, SERM)
could facilitate the tolerance phase rewarding response of methadone. Strikingly,
TMX also reduces tapering/abstinence phases methadone liability in mice. In
conclusion, this study demonstrates altering methadone metabolism through
targeting estrogen signals might be able to free morphine addictive patients from
the addiction of opioid replacement therapy. Therefore, the add-on therapy
clinical trial introducing SERM in MMT regimen is suggested.
PMID- 28699699
TI - Involvement of cholinergic and adenosinergic systems on the branchial immune
response of experimentally infected silver catfish with Streptococcus agalactiae.
AB - It has been recognized that the cholinergic and adenosinergic systems have an
essential role in immune and inflammatory responses during bacterial fish
pathogens, such as the enzymes acetylcholinesterase (AChE) and adenosine
deaminase (ADA), which are responsible for catalysis of the anti-inflammatory
molecules acetylcholine (ACh) and adenosine (Ado) respectively. Thus, the aim of
this study was to investigate the involvement of the cholinergic and
adenosinergic systems on the immune response and inflammatory process in gills of
experimentally infected Rhamdia quelen with Streptococcus agalactiae.
Acetylcholinesterase activity decreased, while ACh levels increased in gills of
infected animals compared to uninfected animals. On the other hand, a significant
increase in ADA activity with a concomitant decrease in Ado levels was observed
in infected animals compared to uninfected animals. Based on this evidence, we
concluded that infection by S. agalactiae in silver catfish alters the
cholinergic and adenosinergic systems, suggesting the involvement of AChE and ADA
activities on immune and inflammatory responses, regulating the ACh and Ado
levels. In summary, the downregulation of AChE activity exerts an anti
inflammatory profile in an attempt to reduce or prevent the tissue damage, while
the upregulation of ADA activity exerts a pro-inflammatory profile, contributing
to disease pathophysiology.
PMID- 28699700
TI - Pharmacogenomics Implementation: Considerations for Selecting a Reference
Laboratory.
AB - One of the initial steps for implementing pharmacogenomics into routine patient
care is selecting an appropriate clinical laboratory to perform the testing. With
the rapid advances in genotyping technologies, many clinical laboratories are now
performing pharmacogenomic testing. Selection of a reference laboratory depends
on whether a particular genotype assay is already performed by an internal health
care organization laboratory or only available externally. Other factors for
consideration are coverage of genomic variants important for the patient
population, technical support, and cost. In some instances, the decision to
select a particular reference laboratory may be the responsibility of the
clinician who is recommending genomic interrogation. Only limited guidance is
available that describes the laboratory characteristics to consider when
selecting a reference laboratory. We provide practical considerations for
selecting a clinical laboratory for pharmacogenomic testing broadly categorized
into four domains: pharmacogene and variant selection; logistics; reporting of
results; and test costs along with reimbursement.
PMID- 28699701
TI - Rictor regulates the vasculogenic mimicry of melanoma via the AKT-MMP-2/9
pathway.
AB - Vasculogenic mimicry (VM)-positive melanomas are usually associated with poor
prognosis. Rictor, the key component of the rapamycin-insensitive complex of mTOR
(mTORC2), is up-regulated in several cancers, especially in melanomas with poor
prognosis. The aim of this study was to investigate the role of Rictor in the
regulation of VM and the mechanism underlying this possible regulation. VM
channels were found in 35 of 81 tested melanoma samples and high Rictor
expression correlated with VM structures. Moreover, Kaplan-Meier survival curves
indicated that VM structures and high Rictor expression correlated with shorter
survival in patients with melanoma. In vitro, Rictor knockdown by short hairpin
RNA (shRNA) significantly inhibited the ability of A375 and MUM-2B melanoma cells
to form VM structures, as evidenced by most tubes remaining open. Cell cycle
analysis revealed that Rictor knockdown blocked cell growth and resulted in the
accumulation of cells in G2/M phase, and cell migration and invasion were greatly
affected after Rictor down-regulation. Western blotting assays indicated that
down-regulating Rictor significantly inhibited the phosphorylation of AKT at
Ser473 and Thr308 , which subsequently inhibited the expression and activity of
downstream MMP-2/9, as confirmed by real-time PCR and gelatin Zymography. MK
2206, a small-molecule inhibitor of AKT, similarly inhibited the activity of AKT
and secretion of MMP-2/9, further supporting that Rictor down-regulation inhibits
the phosphorylation of AKT and activity of downstream MMP-2/9 to affect VM
formation. In conclusion, Rictor plays an important role in melanoma VM via the
Rictor-AKT-MMP-2/9 signalling pathway.
PMID- 28699702
TI - Adult attachment, hostile conflict, and relationship adjustment among couples
facing multiple sclerosis.
AB - OBJECTIVE: Couples facing multiple sclerosis (MS) report significantly elevated
rates of relationship distress, yet the effects of attachment have never been
examined in this population. We examined whether hostile conflict mediated the
dyadic effects of attachment on relationship adjustment in couples facing MS and
whether these associations were moderated by gender or role. We also explored
whether dyadic adjustment mediated the relationship between attachment and
hostile conflict. DESIGN: The study was cross-sectional and included 103 couples
in which one partner had been diagnosed with MS. METHODS: Participants completed
the Experiences in Close Relationships-Revised, Dyadic Adjustment Scale, and
Aversive Interactions Scale, as well as demographic variables. We used the actor
partner interdependence model for data analysis. RESULTS: There were significant
actor and partner effects of greater anxious attachment and worse dyadic
adjustment. Actor and partner effects of anxious attachment were significantly
mediated by greater hostile conflict. Gender significantly moderated the effects
between avoidant attachment and dyadic adjustment. The actor effect was
significant for males and females; the partner effect was only significant for
females. The actor effect for females but not males was significantly mediated by
greater hostile conflict. Role was not a significant moderator. Exploratory
analyses also showed that dyadic adjustment mediated the relationship between
anxious and avoidant attachment and hostile conflict. CONCLUSIONS: Findings
highlight the important effects of attachment on relationship adjustment in MS
couples. Both hostile conflict and dyadic adjustment appear to be mechanisms
through which insecure attachment has a detrimental effect. Statement of
contribution What is already known on this subject? Despite higher-than-normal
rates of marital distress and separation/divorce, the effects of attachment on
relationship adjustment among couples facing multiple sclerosis have never been
examined. Prior studies within healthy populations have supported within-person
and cross-dyadic associations between attachment and relationship adjustment;
however, they have failed to use dyadic analyses. Hostile conflict has been
associated with both insecure attachment and relationship adjustment and
therefore may be an important mediator to help understand these relationships.
What does this study add? Women were more negatively affected by their partner's
avoidant attachment then men. Hostile conflict mediated the effects of anxious
attachment on dyadic adjustment for individuals and across dyads. Hostile
conflict accounted for the individual effect of avoidant attachment on dyadic
adjustment for women.
PMID- 28699704
TI - Aberrant blood-oxygen-level-dependent signal oscillations across frequency bands
characterize the alcoholic brain.
AB - Chronic alcoholism is associated with widespread regional differences from
controls in brain activity and connectivity dynamics measured by blood-oxygen
level-dependent (BOLD) signals. Identification of alcoholism-related
neurofunctional power dynamics using functional magnetic resonance imaging (fMRI)
that relate to cognition and behavior may serve as biomarkers of alcoholism.
Previously, resting-state fMRI studies examined BOLD signals at a single low
frequency (LF) bandwidth. BOLD signals, however, oscillate systematically at
different frequencies and are organized in a resting brain where LF oscillation
facilitates long-distance communication between regions across cortical regions,
whereas high-frequency (HF) oscillation occurs in closely localized, subcortical
areas. Using a frequency power quantification approach, we investigated whether
the organization of BOLD signal oscillations across all measured frequency
bandwidths is altered in alcoholism and relates to cognitive performance.
Frequency-dependent oscillation power differences between 56 sober alcoholics and
56 healthy controls occurred for all frequency bands. Alcoholics exhibited
greater frequency oscillation power in the orbitofrontal cortex and less power in
the posterior insula within the HF bandwidth than controls. Aberrant
orbitofrontal HF power was associated with poorer memory performance and slower
psychomotor speed in alcoholics. Middle-frequency and LF power proved sensitive
in detecting altered frequency oscillation dynamics in parietal and postcentral
cortical regions of alcoholics. This study is novel in identifying alcohol
related differences in BOLD oscillation power of the full fMRI frequency
bandwidth. Specifically, HF power aberrations were associated with poorer
cognitive functioning in alcoholism and may serve as a biomarker for identifying
neural targets for repair.
PMID- 28699703
TI - A positive feedback loop promotes HIF-1alpha stability through miR-210-mediated
suppression of RUNX3 in paraquat-induced EMT.
AB - Irreversible pulmonary fibrosis induced by paraquat (PQ) poisoning is the major
cause of death in patients with PQ poisoning. The epithelial-mesenchymal
transition (EMT) is postulated to be one of the main mechanisms of pulmonary
fibrosis. Here, we investigated the role of miR-210 in PQ-induced EMT and its
relationship with hypoxia-inducible factor-1alpha (HIF-1alpha). Western blotting,
immunofluorescence, immunoprecipitation and other methods were used in this
study. We found that miR-210 expression was significantly increased after PQ
poisoning, and it may be regulated by HIF-1alpha. Overexpression of miR-210
further increased the HIF-1alpha protein level and promoted EMT. Moreover, miR
210 knock-down reduced the HIF-1alpha protein level and decreased the degree of
EMT. Runt-related transcription factor-3 (RUNX3), a direct target of miR-210, was
inhibited by miR-210 in response to PQ poisoning. RUNX3 increased the
hydroxylation ability of prolyl hydroxylase domain-containing protein 2 (PHD2), a
key enzyme that promotes HIF-1alpha degradation. PHD2 immunoprecipitated with
RUNX3 and its level changed similarly to that of RUNX3. The expression of the HIF
1alpha protein was significantly reduced when RUNX3 was overexpressed. HIF-1alpha
protein levels were markedly increased when RUNX3 was silenced. Based on these
results, a positive feedback loop may exist between miR-210 and HIF-1alpha. The
mechanism may function through miR-210-mediated repression of RUNX3, which
further decreases the hydroxylation activity of PHD2, enhances the stability of
HIF-1alpha, and promotes PQ-induced EMT, aggravating the progression of pulmonary
fibrosis. This study further elucidates the mechanism of PQ-induced pulmonary
fibrosis and may provide a new perspective for the future development of
therapies.
PMID- 28699705
TI - Organic Dye Adsorption by Amphiphilic Tris-Urea Supramolecular Hydrogel.
AB - The development of an effective adsorbent for cleansing polluted water is
required for environmental purification. In this respect, a supramolecular
hydrogel constructed by the self-assembly of small molecules could be a strong
candidate. Adsorption experiments of organic dyes were performed using
supramolecular hydrogels of amphiphilic tris-urea 1. Cationic organic dyes were
adsorbed efficiently; indeed, the adsorption of methylene blue was as high as
4.19 mol equivalents relative to 1. Two luminescence peaks were observed in the
rhodamine 6G-adsorbed supramolecular hydrogels, and their ratios varied with the
amount of dye adsorbed. Fluorescence microscopy images of the supramolecular
hydrogel at lower dye levels exhibited fibrous fluorescence consistent with the
fibrous aggregates of 1. According to these results, adsorption may proceed
gradually, that is, occurring initially on the fibers and later in the aqueous
spaces of the supramolecular hydrogel.
PMID- 28699706
TI - ?
PMID- 28699707
TI - [Electrocardiographic interpretation in athletes : 2017 recommendations for non
cardiologists].
AB - A resting electrocardiogram (ECG) is recommended for screening of sudden cardiac
death in young athletes. However, ECG interpretation in athletes requires an
adequate training because normal physiological training adaptations in athletes
can sometimes be hardly distinguished from abnormal findings suggestive of
underlying pathology. In 2017, a consensus of international experts established
new recommendations for a clear and accurate interpretation of ECGs in athletes.
This article aims to guide non-cardiologists according to these new data,
allowing a better triage of anomalies requiring further investigations.
PMID- 28699708
TI - [Immersion pulmonary edema].
AB - Immersion pulmonary edema may occur during scuba diving, snorke-ling or swimming.
It is a rare and often recurrent disease, mainly affecting individuals aged over
50 with high blood pressure. However it also occurs in young individuals with a
healthy heart. The main symptoms are dyspnea, cough and hemoptysis. The outcome
is often favorable under oxygen treatment but deaths are reported. A cardiac and
pulmonary assessment is necessary to evaluate the risk of recurrence and possible
contraindications to immersion.
PMID- 28699709
TI - [Sport-related concussion].
AB - Sport-related concussion is a frequent and complex pathology whose
physiopathological mechanisms are not completely understood yet. A recent
consensus statement has been published with the objective to provide
practicioners with an overview of literature and give some guidelines based on
the current state of knowledge. An 11R approach (Recognise, Remove, Re-evaluate,
Rest, Rehabilitation, Refer, Recover, Return to sport, Reconsider, Residual
effects and sequelae, Risk reduction) is proposed to evaluate and manage sport
related concussion. There is currently no available test predicting recovery, but
the risk factors for a slow recovery are now known. Return to daily activities
(as school) and to full sport participation should follow the graduated return-to
school or - sport strategy, and the ultimate decision is clinically based, and
made by the physician.
PMID- 28699710
TI - [" My joints are cracking, is it serious doctor ? " A review about sounds
produced by joints].
AB - The sounds produced by joints are a common source of questioning for doctors and
their patients. Two major types are identified : cracks and crepitus. Few
investigations have been carried out on these manifestations, while they
potentially have clinical implications, especially for patellar crepitus in
patellofemoral osteoarthrosis, and may generate anxiety. Knuckle cracking appears
to be caused by the sudden and temporary occurrence of an intra-articular gaseous
cavity, called tribonucleation. Other researches on these sounds are focused on
the knees and their links with osteoarthritis, as well as on the spine. Many
questions still arise but it seems important to talk about it with patients
without trivializing them.
PMID- 28699711
TI - [How to choose the ideal graft for anterior cruciate ligament reconstruction].
AB - Indication for anterior cruciate ligament reconstruction is a debated subject and
needs to be discussed on an individual basis, depending on the patient's age and
physical demands. Graft selection is a crucial step for successful outcome and
needs to be adapted to the patient, to the concomitant lesions, preoperative knee
and lower limb injuries, but also to the surgeon's experience and preference. The
present article summarizes current concepts, the pros and cons of the most used
autografts and allografts, and highlights the importance to adapt postoperative
rehabilitation in function of the graft.
PMID- 28699712
TI - [Importance of play : little health promoting review for children and their
families].
AB - Children love to play; play is their favorite occupation. They flourish through
this millennial occupation. Play promotes harmonious development while
integrating principles of social life. It is a solid barrier against the growing
harms of sedentary lifestyle. The evolution of our societies is marked from the
earliest age by a breathtaking decrease in the amount of movement and playtime of
children. The consequences are known: delayed psychomotor development,
psychological disorders, progression of obesity. Children of pre-carious and
vulnerable families are the first victims. This review high-lights some of the
essential knowledge related to the importance of play in children aged 0 to 5
years and attempts to suggest issues for recovering from a compromised situation.
Solutions are individual, family and societal. The essential role of the family
physician is specified.
PMID- 28699713
TI - [Potential role of norepinephrine in the immune dysfunction associated with
sepsis].
AB - Septic shock may be complicated by a state of immune suppression, with ominous
prognosis significance. Although the underlying pathophysiological mechanisms are
poorly understood, it is possible that norepinephrine, used to treat circulatory
failure during septic shock, plays a significant contributing role. Indeed,
besides its hemodynamic effects, norepinephrine exerts multiple immunosuppressive
actions, which are primarily mediated by beta-2 adrenergic receptors expressed by
immune cells. Furthermore, norepinephrine has the ability to promote the growth
of numerous bacteria, and could thereby foster the development of nosocomial
infections. Norepinephrine being one of the most prescribed drugs in intensive
care medicine, knowledge of these particular immunological effects is essential
for the intensive care physicians.
PMID- 28699714
TI - ?
PMID- 28699715
TI - ?
PMID- 28699716
TI - ?
PMID- 28699717
TI - ?
PMID- 28699718
TI - ?
PMID- 28699719
TI - Which functional outcome parameters correlate better with elderly patients'
satisfaction after non-fusion lumbar spine surgery?
AB - BACKGROUND: Elderly patients are increasingly operated for spinal degenerative
diseases. The treatment objective is quality of life, which, in this population,
is difficult to assess. Hence, patient satisfaction, although less objective, is
of high importance. In this study, we have examined the relation of various
functional parameters after non-fusion spinal surgery, with patient satisfaction.
PATIENTS AND METHODS: A 5-year follow-up after non-fusion lumbar spine surgery on
185 elderly patients was performed. Demographics, co-morbidity factors, type of
lesion and operation performed were recorded. The Oswestry Disability Index (ODI)
was calculated. Also, walking distance, use of analgesics, daily activities,
social life and patient mobility were assessed by means of study-specific
stratified pain- independent questionnaires. Finally, patient satisfaction was
assessed by the single- item satisfaction question. RESULTS: Post-operative ODI,
and the improvement regarding ODI, analgesic use and walking distance indices
were independent factors influencing patient satisfaction. The insertion of pain
analog scale score into this model altered the results, and along with this
score, only the walking distance improvement remained an independent
statistically significant factor. When the independent from pain scales were
used, the improvement of the walking distance score were independently related to
the satisfaction of the elderly. CONCLUSIONS: ODI is applicable in elderly
patients, even with the exception of some of the categories assessed. Walking
capacity should be assessed separately from other pain-dependent activities; its
improvement should be an independent goal of lumbar spine surgery in the elderly.
The level of the elderly patient subjectivity in auto- assessing the outcome of
lumbar spine surgery is high, and objective outcome measurements remain
important.
PMID- 28699720
TI - In vitro cytotoxic activity evaluation of phenytoin derivatives against human
leukemia cells.
AB - Hydantoin derivatives, including phenytoin (5,5-diphenylhydantoin), have recently
gained attention as they possess a variety of important biochemical and
pharmacological properties. Nevertheless, available information on anticancer
activity of hydantoin derivatives is still scarce. Here, we evaluated possible
antileukemic potential of four phenytoin analogs, namely: methyl 2-(2,4-dioxo-5,5
diphenylimidazolidin-3-yl)propanoate (1), methyl 2-(1-(3-bromopropyl)-2,4-dioxo
5,5-diphenylimidazolidin-3-yl)propanoate (2), 1-(3-bromopropyl)-3-methyl-5,5
diphenylimidazolidine-2,4-dione (3) and 1-(3-bromobutyl)-3-methyl-5,5
diphenylimidazolidine-2,4-dione (4). The experiments were performed on human
acute histiocytic lymphoma U937 cells and human promyelocytic leukemia HL-60
cells. The present study was conducted using spectrophotometric 3-[4,5
dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) assay and the
electronic Beckman-Coulter method. We observed temporary changes in the leukemia
cell viability, volume and count. The effects of the four 5,5-diphenylhydantoin
derivatives on U937 and HL-60 cells depended on the agent tested and its
concentration, the time intervals after the compound application, and the
leukemia cell line used. HL-60 cells were more sensitive than U937 cells to the
action of the phenytoin analogs (1-4). The antileukemic activities of the three
bromoalkyl diphenylhydantoin derivatives (2, 3, and 4) were stronger than that of
the compound 1 [methyl 2-(2,4-dioxo-5,5-diphenylimidazolidin-3-yl) propanoate],
with no bromoalkyl substituent. The structural modifications of 5,5
diphenylhydantoin are responsible for such varied antileukemic potential of its
four derivatives.
PMID- 28699721
TI - Comparison of pre- and post-ischemic treatment of telmisartan and nimodipine
combination in experimentally induced cerebral ischemia.
AB - Time dependent intervention plays a crucial role in preventing neurodegeneration
after ischemic insult. The intensity of excitotoxicity is greater in the
secondary reperfusion phase (2-4 h) compared to the primary occlusion phase (2
h), which could be attributed to secondary elevation of excitatory amino acids
(EAA) in cerebral ischemia. In the present study, we tried to assess the
neuroprotective effects of telmisartan and nimodipine (TM-NM) combination on the
secondary reperfusion phase. The drug treatments were made immediately after
reperfusion and their effects were compared with pre-treatment. The
neuroprotective effect was studied using middle cerebral artery occlusion (MCAo)
transient ischemic model in rats. On the 7th day after reperfusion, the rats were
subjected to behavioral studies. The brain was dissected out on the 9th day to
measure neurobiochemical alterations and for histopathological observations. The
results have shown that TM-NM (5 mg/kg) attenuated the EAA release in different
brain regions with partial restoration of energy levels in secondary reperfusion
phase. Similarly, it normalized the behavioral alteration and the effect was
comparable to pre-ischemic treatment (2.5 mg/kg). Pre-ischemic treatment of TM-NM
(2.5 mg/kg) protected the neurons from ischemic reperfusion injury by energy
dependent EAA regulation. It can be concluded from the study that, even though
the pre- and post-treatment of TM-NM show similar results, the post-ischemic
treatment of TM-NM combination is beneficial due to better EAA control. Since
hypertension is the primary risk factor for stroke, clinical incidents of stroke
in hypertensive patients receiving angiotensin receptor blockers (ARBs) can be
further investigated to understand the present study in the clinical situation.
PMID- 28699722
TI - Antinociceptive, anti-inflammatory and antiarthritic activities of Bungarus
fasciatus venom in experimental animal models.
AB - Pain and inflammation are intimately associated with rheumatoid arthritis, a
growing bone-joint related problem of the modern society. Though several
therapeutic managements are available for arthritis, their side effects not only
limit their use, but also advocate the quest for natural therapies. In this
study, we explored the antinociceptive, anti-inflammatory and antiarthritic
activities of Bungarus fasciatus venom (BFV) in experimental animal models.
Rheumatoid arthritis was induced by Freund's complete adjuvant (FCA) in male
Wistar albino rats. Lyophilized BFV was diluted in 0.9% NaCl. Antiarthritic
activity showed that BFV significantly reduced the paw and ankle diameters;
urinary hydroxyproline, glucosamine levels and serum ACP/ALP/TNF-alpha/IL
1beta/IL-17/Cathepsin-K/MMP-1 levels. These parameters were significantly
increased in FCA induced arthritic animals. Joint histopathology study indicated
the partial restoration of joint structure. Treatment with BFV significantly
reduced the mean latency time of tail flick response, acetic acid induced
writhing response and formalin induced licking response in male albino mice. BFV
treatment also significantly reduced carrageenan induced paw edema and xylene
induced ear edema in male albino mice. The results indicated that BFV possess
antinociceptive, anti-inflammatory and antiarthritic properties and further
studies are warranted to find the active constituents present in BFV.
PMID- 28699723
TI - Fermentation, isolation, purification and characterization of an antitubercular
antibiotic from Streptomyces luridus MTCC 4402.
AB - Tuberculosis, caused by Mycobacterium tuberculosis, continues to be a serious
public health problem around the world, and it urges the need for development of
new antitubercular drugs. An antibiotic producing strain, Streptomyces luridus
(MTCC 4402) was earlier isolated from soil by our group. In this work, the
phylogenic status was established by 16S rRNA gene sequence analysis. The strain
was found to be active against clinically resistant strains. The culture was
grown in shake flasks in a medium containing cornsteep liquor, glucose, CaCO(3),
soyabean meal and starch. Antibiotic production reached maximum at the end of 72
h. and fermentation profile was obtained. The active compound was extracted into
ethyl acetate and was subjected to activity guided purification by column
chromatography using silica gel, TLC and HPLC methods. The pure compound eluted
at 16.7 min. by gradient elution was subjected to (1)H, (13)C NMR and mass
spectral analyses. The acquired data was compared with that of natural products'
data base and found to be a known antibiotic, spiramycin. The purified compound
was studied for mutagenic, cytotoxicity, antitubercular activities. It was non
mutagenic at the concentration of 1000 MUg/mL, non cytotoxic and active as
antitubercular agent at a concentration of 64 mg/mL and was comparable to
rifampicin.
PMID- 28699724
TI - Toxicity of Bacillus thuringiensis Cry2Ab and the inheritance of Cry2Ab
resistance in the Pink bollworm, Pectinophora gossypiella (Saunders).
AB - Though the insecticidal crystal (Cry) proteins produced by Bacillus thuringiensis
(Bt) are effective against insect pests, evolution of resistance remains an issue
of great concern. Here, we explored the ability of pink bollworm, Pectinophora
gossypiella (Lepidoptera: Gelechiidae), a key pest of cotton, to evolve
resistance to Cry2Ab and characterized it in terms of inheritance. Sixteen day
bioassay of Bt Cry2Ab toxin against 5-day old pink bollworm larvae showed median
lethal concentration (LC(50)) ranging 0.16-1.44 ug/g diet for five different
populations collected from Srivilliputtur (Tamil Nadu), Jalgaon (Maharashtra),
Bharuch (Gujarat), New Delhi (Delhi) and Sri Ganganagar (Rajasthan). Selection of
pink bollworm for evolution of Cry2Ab resistance led to the maximal of 37.75-fold
resistance vis-a-vis the most susceptible strain. Further studies on inheritance
using above parental populations showed autosomal and semidominant nature of
Cry2Ab resistance, with dominance h values of 0.69 and 0.79 for two reciprocal
crosses. The inheritance of Cry2Ab resistance appeared to be governed by multiple
alleles/genes. Cry2Ab resistance was associated with fitness costs in terms of
prolonged larval and pupal period when resistant parent population was reared on
the diet without toxin. Fitness cost in terms of larval period appeared to be
inherited in F(1), F(2) and backcross progenies. F(2) progeny also inherited
these differences in larval and pupal periods. These studies clearly advocate
rigorous monitoring of Cry2Ab resistance and compliance of resistance management
in the pink bollworm for ensuring Bt cotton sustainability.
PMID- 28699725
TI - Evaluation of candidate reference genes for quantitative expression studies in
Asian seabass (Lates calcarifer) during ontogenesis and in tissues of healthy and
infected fishes.
AB - Quantitative real-time PCR (qRT-PCR), used to determine the gene expression
profile, is an important tool in functional genomic research, including fishes.
To obtain more robust and meaningful result, the best possible normalization of
the data is of utmost significance. In the present study, we have evaluated the
potential of five commonly used housekeeping genes i.e., elongation factor 1
alpha (EF1A), beta-Actin (ACTB), 18S ribosomal RNA (18S), glyceraldehyde-3
phosphate dehydrogenase (GAPDH) and beta-2-Microglobulin (B2M) in normal
physiological conditions, developmental stages and in response to bacterial
infection in Asian seabass, Lates calcarifer (Bloch), an important food fish
cultured in the Asia-Pacific region. The expression levels of these five genes
were estimated in 11 tissues of normal seabass juveniles, 14 embryonic and larval
developmental stages and six tissues of Vibrio alginolyticus-challenged animals.
Further, the expression stability of these genes was calculated based on three
algorithms i.e. geNorm, NormFinder and BestKeeper. The results showed that
although there are tissue-specific variations for each gene, ACTB and EF1A are
the most stable genes across the tissues of normal animals. However, in bacteria
challenged animals, EF1A and 18S were found to be the best reference genes for
data normalization. The expression of all the genes tested showed an increasing
trend in developmental stages and the increase was significant at blastula stage.
Among the five genes tested, EF1A and ACTB were found to be the genes with least
variation and highest stability across the developmental stages. This forms the
first report on validation of housekeeping genes in L. calcarifer, in the context
of ontogenic development and in response to infection.
PMID- 28699726
TI - In vitro digestibility study of some plant protein sources as aquafeed for carps
Labeo rohita and Cyprinus carpio using pH-Stat method.
AB - Aquaculture, as a promising food industry, is expected to meet the demand for
quality food from the increasing human population. As the diet is critical for
feeding farm fish, such a faster growth in the industry is destined to create
stress in the fishmeal market to supply diets to the tune. In this context, here,
we studied the protein content of 20 plant ingredients, including aquatic weeds,
cereals, pulses and oil-cakes using micro-Kjeldahl method and evaluated in vitro
digestibility of these ingredients for rohu Labeo rohita and common carp Cyprinus
carpio using pH-Stat method. The protein contents of water fern, duckweed, almond
oil-cake and soybean product were 20.81, 39.75, 47.78 and 57.48%, respectively.
Species-specific digestibility was found for the same plant ingredient. The
degree of hydrolysis for water fern, duck weed, almond oil-cake and soybean
product were 14.17, 4.80, 17.30 and 3.57%, respectively for rohu and 4.58, 6.03,
12.17 and 3.35%, respectively for common carp. This study showed that
incorporation of water fern and almond oil-cake in the diet of rohu, and duck
weed and almond oil-cake in the diet of common carp are beneficial considering
their protein content and digestibility. These are cost-effective, protein-rich
feed ingredients for aquafeed.
PMID- 28699727
TI - Assessment of prophylactic effect of Senna auriculata (L.) Roxb. leaves on
alcohol-induced pancreatitis in rat model.
AB - Aqueous leaf extract of Senna auriculata (L.) Roxb. syn. Cassia auriculata (SLEx)
is known to possess potential antidiabetic and antioxidant properties. Based on
the known correlation between exocrine pancreatic function and endocrine
secretary capacity, here, we studied the prophylactic effect of the SLEx on
alcohol induced pancreatitis in rats. To induce chronic pancreatitis, the rats
were fed with unsaturated fat i.e. corn oil (2.5 mL/kg) along with high dose of
ethanol (10.2 g/kg) for 4 wk, and was increased 0.6 g/kg after every 2 days for 1
wk and then 0.6 g/kg after every 4 days for a period of 4 wk. SLEx was orally
administered to rats at dose of 400 mg/kg/day for 4 wk. At the end of 4th wk,
pancreatic enzymes i.e., alpha-amylase, lipase, serum and pancreatic MDA levels
were estimated. Pancreatic histopathological studies were also performed. The
SLEx significantly reduced the serum levels of alpha-amylase and lipase along
with significant suppression in serum and pancreatic tissue lipid peroxidation.
Histomorphological studies did not show any fatty vacoules in acinar cells of
SLEx-treated rats. However, vacoulation was seen in acini of pathogenic control
rats. With the results, we conclude that Senna auriculata aqueous leaf extract
has potential to reduce the ethanol-induced pathogenecity, and it possesses
prophylactic effect on alcohol-induced pancreatitis. However, a long term trial
is needed to ascertain its therapeutic potential for pancreatitis.
PMID- 28699728
TI - Electroosmotic Flow Dispersion of Large Molecules in Electrokinetic Migration.
AB - It is a common knowledge that large molecules have small diffusion coefficients.
Therefore, it was thought that these molecules should generate very narrow peaks
in electropherograms, because longitudinal diffusion was thought to be the only
factor that contributes to band broadening in electrophoretic separation systems
in capillaries and microfluidics. However, it is also common to observe that
large molecules such as proteins and polymers often produce wider peaks than most
small molecules. It is demonstrated in this work that dispersion of analytes
during electrokinetic migration is also the results of Taylor dispersion. Similar
to conventional Taylor dispersion, peak broadening is more pronounced for
particles with smaller diffusion coefficients. The theoretical description of
band broadening caused by electroosmotic flow dispersion (EOFD) and the
experimental verification of this phenomenon are presented in this paper. The
dispersion of various sized molecules, from small peptides to large proteins, in
capillary electrophoresis is used as examples in this study.
PMID- 28699729
TI - Room-Temperature Multiferroics and Thermal Conductivity of 0.85BiFe1-2xTixMgxO3
0.15CaTiO3 Epitaxial Thin Films (x = 0.1 and 0.2).
AB - Thin films of 0.85BiFe1-2xTixMgxO3-0.15CaTiO3 (x = 0.1 and 0.2, abbreviated to C
1 and C-2, respectively) have been fabricated on (001) SrTiO3 substrate with and
without a conductive La0.7Sr0.3MnO3 buffer layer. The X-ray theta-2theta and phi
scans, atomic force microscopy, and cross-sectional transmission electron
microscopy confirm the (001) epitaxial nature of the thin films with very high
growth quality. Both the C-1 and C-2 thin films show well-shaped magnetization
magnetic field hysteresis at room temperature, with enhanced switchable
magnetization values of 145.3 and 42.5 emu/cm3, respectively. The polarization
electric loops and piezoresponse force microscopy measurements confirm the room
temperature ferroelectric nature of both films. However, the C-1 films illustrate
a relatively weak ferroelectric behavior and the poled states are easy to relax,
whereas the C-2 films show a relatively better ferroelectric behavior with stable
poled states. More interestingly, the room-temperature thermal conductivity of C
1 and C-2 films are measured to be 1.10 and 0.77 W/(m.K), respectively. These
self-consistent multiferroic properties and thermal conductivities are discussed
by considering the composition-dependent content and migration of Fe-induced
electrons and/or charged point defects. This study not only provides
multifunctional materials with excellent room-temperature magnetic,
ferroelectric, and thermal conductivity properties but may also stimulate further
work to develop BiFeO3-based materials with unusual multifunctional properties.
PMID- 28699730
TI - Flexible Slippery Surface to Manipulate Droplet Coalescence and Sliding, and Its
Practicability in Wind-Resistant Water Collection.
AB - A flexible slippery membrane (FSM) with tunable morphology and high elastic
deformability has been developed by infusing perfluoropolyether (PFPE) into a
fluorinated-copolymer-modified thermoplastic polyurethane (TPU) nanofiberous
membrane. To immobilize PFPE in TPU matrix, we synthesized a fluorinated
copolymer poly(DFMA-co-IBOA-co-LMA) with low surface energy, high chemical
affinity to PFPE, adequate flexibility, and strong physical adhesion on TPU. Upon
external tensile stress, the as-prepared FSM can realize a real-time manipulation
of water sliding and coalescence on it. Furthermore, it exhibits the ability to
preserve the captured water from being blown away by strong wind, which ensures
the water collection efficiency in windy regions.
PMID- 28699731
TI - In Situ Grown S Nanosheets on Cu Foam: An Ultrahigh Electroactive Cathode for
Room-Temperature Na-S Batteries.
AB - Room-temperature sodium-sulfur batteries are competitive candidates for large
scale stationary energy storage because of their low price and high theoretical
capacity. Herein, pure S nanosheet cathodes can be grown in situ on three
dimensional Cu foam substrate with the condensation between binary polymeric
binders, serving as a model system to investigate the formation and
electrochemical mechanism of unique S nanosheets on the Cu current collectors. On
the basis of the confirmed conversion reactions to Na2S, The constructed cathode
exhibits ultrahigh initial discharge/charge capacity of 3189/1403 mAh g-1. These
results suggest that there is great potential to optimize S cathode by exploiting
low-cost Cu substrates instead of conventional Al current collectors.
PMID- 28699732
TI - Fundamental and Practical Insights on the Packing of Modern High-Efficiency
Analytical and Capillary Columns.
AB - New stationary phases are continuously developed for achieving higher
efficiencies and unique selectivities. The performance of any new phase can only
be assessed when the columns are effectively packed under high pressure to
achieve a stable bed. The science of packing columns with stationary phases is
one of the most crucial steps to achieve consistent and reproducible high
resolution separations. A poorly packed column can produce non-Gaussian peak
shapes and lower detection sensitivities. Given the ever larger number of
stationary phases, it is impossible to arrive at a single successful approach.
The column packing process can be treated as science whose unified principles
remain true regardless of the stationary phase chemistry. Phenomenologically, the
column packing process can be considered as a constant pressure or constant flow
high-pressure filtration of a suspension inside a column with a frit at the end.
This process is dependent on the non-Newtonian suspension rheology of the slurry
in which the particles are dispersed. This perspective lays out the basic
principles and presents examples for researchers engaged in stationary phase
development. This perspective provides an extensive set of slurry solvents,
hardware designs, and a flowchart, a logical approach to optimal column packing,
thus eliminating the trial and error approach commonly practiced today. In
general, nonaggregating but high slurry concentrations of stationary phases tend
to produce well packed analytical columns with small particles. Conversely, C18
packed capillary columns are best packed using agglomerating solvents.
PMID- 28699733
TI - Diversity of Alkylproline Moieties in Pyrrolobenzodiazepines Arises from
Postcondensation Modifications of a Unified Building Block.
AB - Anticancer pyrrolobenzodiazepines (PBDs) are one of several groups of natural
products that contain unusual 4-alkyl-l-proline derivatives (APDs) in their
structure. APD moieties of PBDs are characterized by high structural diversity
achieved through unknown biosynthetic machinery. Based on LC-MS analysis of
culture broths, feeding experiments, and protein assays, we show that APDs are
not incorporated into PBDs in their final form as was previously hypothesized.
Instead, a uniform building block, 4-propylidene-l-proline or 4-ethylidene-l
proline, enters the condensation reaction. The subsequent postcondensation steps
are initiated by the introduction of an additional double bond catalyzed by a FAD
dependent oxidoreductase, which we demonstrated with Orf7 from anthramycin
biosynthesis. The resulting double bond arrangement presumably represents a
prerequisite for further modifications of the APD moieties. Our study gives
general insight into the diversification of APD moieties of natural PBDs and
provides proof-of-principle for precursor directed and combinatorial biosynthesis
of new PBD-based antitumor compounds.
PMID- 28699734
TI - Solution and Solid-State Nuclear Magnetic Resonance Structural Investigations of
the Antimicrobial Designer Peptide GL13K in Membranes.
AB - The antimicrobial peptide GL13K encompasses 13 amino acid residues and has been
designed and optimized from the salivary protein BPIFA2 to exhibit potent
bacteriocidal and anti-biofilm activity against Gram-negative and Gram-positive
bacteria as well as anti-lipopolysaccharide activity in vitro and in vivo. Here,
the peptide was analyzed in a variety of membrane environments by circular
dichroism spectroscopy and by high-resolution multidimensional solution nuclear
magnetic resonance (NMR) spectroscopy. Whereas in the absence of membranes a
random coil conformation predominates, the peptide adopts a helical structure
from residue 5 to 11 in the presence of dodecylphosphocholine micelles. In
contrast, a predominantly beta-sheet structure was observed in the presence of
lipid bilayers carrying negatively charged phospholipids. Whereas 15N solid-state
NMR spectra are indicative of a partial alignment of the peptide 15N-1H vector
along the membrane surface, 2H and 31P solid-state NMR spectra indicate that in
this configuration the peptide exhibits pronounced disordering activities on the
phospholipid membrane, which is possibly related to antimicrobial action. GL13K,
thus, undergoes a number of conformational transitions, including a random coil
state in solution, a helical structure upon dilution at the surface of
zwitterionic membranes, and beta-sheet conformations at high peptide:lipid
ratios.
PMID- 28699735
TI - pi-Conjugate Fluorophore-Tagged and Enzyme-Responsive l-Amino Acid Polymer
Nanocarrier and Their Color-Tunable Intracellular FRET Probe in Cancer Cells.
AB - The present investigation accounts one of the first example of enzyme-responsive
and pi-conjugate-tagged l-amino acid amphiphilic polymer and their fluorescence
resonance energy transfer (FRET) probes for color-tunable intracellular
bioimaging in cancer cells. Melt polymerizable oligo-phenylenevinylene (OPV) pi
conjugated diol was tailor-made and subjected to thermo-selective melt
transesterification reaction with multifunctional l-aspartic acid monomer to
yield OPV-tagged amphiphilic luminescent polyesters. These amphiphilic polyesters
self-assembled through strong aromatic pi-pi stacking and hydrophilic/hydrophobic
noncovalent forces into <200 nm size blue-luminescent nanoparticles in aqueous
medium. The OPV-tagged polymer nanoparticles served as FRET donor and
encapsulated water insoluble Nile Red (NR) fluorophore as a FRET acceptor. Detail
photophysical studies revealed that both the OPV and NR were confined within
Forster distance in the polymer nanocontainer and the nanodomains provided
appropriate geometry for efficient excitation energy transfer from OPV to NR.
Cytotoxicity studies in breast cancer (MCF 7), cervical cancer (HeLa) and normal
(Wild-type MEF) cell lines revealed that both the nascent luminescent OPV
nanoparticles and OPV-NR FRET probes were nontoxic to cells up to 100 MUg/mL.
Confocal microscope images confirmed the efficient transportation of polymer and
FRET probes across the cell membranes and their preferable accumulation in the
cytoplasm of the cells. Lysosomal tracker assisted live cell imaging provided
direct evidence for the localization of the polymer nanoparticles at the
lysosomal compartments in the cytoplasm. In vitro enzyme-responsive studies
revealed that the aliphatic polyester backbone in the polymer nanoparticles was
readily biodegradable by lysosomal enzymes like esterase, chymotrypsin, trypsin,
and also redox GSH species in the cytoplasm. Selective photoexcitation in
confocal microscope exhibited bright OPV blue-luminescence and strong red
emission from NR followed by the excitation energy transfer and occurrence of
FRET process at the intracellular environment in cancer cell lines. Both the
polymer design and the biodegradable polymer FRET concept are completely new;
thus, the present approach opens up new platform of research opportunities for
natural l-amino acid based luminescent polymer probes for color-tunable
bioimaging in cancer cells.
PMID- 28699736
TI - Detection of an Integrin-Binding Mechanoswitch within Fibronectin during Tissue
Formation and Fibrosis.
AB - Fibronectin (Fn) is an extracellular matrix protein that orchestrates complex
cell adhesion and signaling through cell surface integrin receptors during tissue
development, remodeling, and disease, such as fibrosis. Fn is sensitive to
mechanical forces in its tandem type III repeats, resulting in extensive
molecular enlongation. As such, it has long been hypothesized that cell- and
tissue-derived forces may activate an "integrin switch" within the critical
integrin-binding ninth and 10th type III repeats-conferring differential integrin
binding specificity, leading to differential cell responses. Yet, no direct
evidence exists to prove the hypothesis nor demonstrate the physiological
existence of the switch. We report direct experimental evidence for the Fn
integrin switch both in vitro and ex vivo using a scFv engineered to detect the
transient, force-induced conformational change, representing an opportunity for
detection and targeting of early molecular signatures of cell contractile forces
in tissue repair and disease.
PMID- 28699737
TI - Extending the Use of Highly Porous and Functionalized MOFs to Th(IV) Capture.
AB - Thorium separation has recently become a hot topic because of the potential
application of thorium as a future nuclear fuel, while metal-organic framework
(MOF) materials have received much attention in the separation field due to their
unique properties. Herein, a highly porous and stable MOF, UiO-66, and its
carboxyl derivatives (UiO-66-COOH and UiO-66-(COOH)2) were synthesized and
explored for the first time for Th(IV) capture from a weak acidic solution.
Although the introduction of carboxyl groups into UiO-66 leads to an obvious
decrease in the surface area and pore volume, the adsorbability toward Th(IV) is
greatly enhanced. At pH = 3.0, the saturated sorption capacity for Th(IV) into
UiO-66-(COOH)2 reached 350 mg/g, representing one of the largest values for
Th(IV) capture by solid extraction. Moreover, the functionalized MOFs show fast
sorption kinetics and desirable selectivity toward Th(IV) over a range of
competing metal ions. A possible mechanism for the selective recognition of
Th(IV) by these MOFs was explored on the basis of extended X-ray absorption fine
structure and Fourier transform infrared analysis. It is concluded that UiO-66
COOH and UiO-66-(COOH)2 sorb Th(IV) through the coordination of carboxyl anions
in the pores of the MOFs, whereas in the case of UiO-66, both the precipitation
and the exchange with the organic solvent contribute to the Th(IV) uptake. This
study contributes to the assessment of the feasibility of MOFs applied in
actinides separation and better understanding of actinides sorption behavior in
this kind of hybrid porous solid materials.
PMID- 28699738
TI - A Molecular Combination of Zinc(II) Phthalocyanine and Tamoxifen Derivative for
Dual Targeting Photodynamic Therapy and Hormone Therapy.
AB - The combination of photodynamic therapy and other cancer treatment modalities is
a promising strategy to enhance therapeutic efficacy and reduce side effects. In
this study, a tamoxifen-zinc(II) phthalocyanine conjugate linked by a triethylene
glycol chain has been synthesized and characterized. Having tamoxifen as the
targeting moiety, the conjugate shows high specific affinity to MCF-7 breast
cancer cells overexpressed estrogen receptors (ERs) and tumor tissues, therefore
leading to a cytotoxic effect in the dark due to the cytostatic tamoxifen moiety,
and a high photocytotoxicity due to the photosensitizing phthalocyanine unit
against the MCF-7 cancer cells. The high photodynamic activity of the conjugate
can be attributed to its high cellular uptake and efficiency in generating
intracellular reactive oxygen species. Upon addition of exogenous 17beta
estradiol as an ER inhibitor, the cellular uptake and photocytotoxicity of the
conjugate are reduced significantly. As shown by confocal microscopy, the
conjugate is preferentially localized in the lysosomes of the MCF-7 cells.
PMID- 28699739
TI - Atomic Layer Engineering of High-kappa Ferroelectricity in 2D Perovskites.
AB - Complex perovskite oxides offer tremendous potential for controlling their rich
variety of electronic properties, including high-TC superconductivity, high-kappa
ferroelectricity, and quantum magnetism. Atomic-scale control of these intriguing
properties in ultrathin perovskites is an important challenge for exploring new
physics and device functionality at atomic dimensions. Here, we demonstrate
atomic-scale engineering of dielectric responses using two-dimensional (2D)
homologous perovskite nanosheets (Ca2Nam-3NbmO3m+1; m = 3-6). In this homologous
2D material, the thickness of the perovskite layers can be incrementally
controlled by changing m, and such atomic layer engineering enhances the high
kappa dielectric response and local ferroelectric instability. The end member (m
= 6) attains a high dielectric constant of ~470, which is the highest among all
known dielectrics in the ultrathin region (<10 nm). These results provide a new
strategy for achieving high-kappa ferroelectrics for use in ultrascaled high
density capacitors and post-graphene technology.
PMID- 28699740
TI - Design, Synthesis, and Evaluation of the Highly Selective and Potent G-Protein
Coupled Receptor Kinase 2 (GRK2) Inhibitor for the Potential Treatment of Heart
Failure.
AB - A novel class of therapeutic drug candidates for heart failure, highly potent and
selective GRK2 inhibitors, exhibit potentiation of beta-adrenergic signaling in
vitro studies. Hydrazone derivative 5 and 1,2,4-triazole derivative 24a were
identified as hit compounds by HTS. New scaffold generation and SAR studies of
all parts resulted in a 4-methyl-1,2,4-triazole derivative with an N
benzylcarboxamide moiety with highly potent activity toward GRK2 and selectivity
over other kinases. In terms of subtype selectivity, these compounds showed
enough selectivity against GRK1, 5, 6, and 7 with almost equipotent inhibition to
GRK3. Our medicinal chemistry efforts led to the discovery of 115h (GRK2 IC50 =
18 nM), which was obtained the cocrystal structure with human GRK2 and an
inhibitor of GRK2 that potentiates beta-adrenergic receptor (betaAR)-mediated
cAMP accumulation and prevents internalization of betaARs in beta2AR-expressing
HEK293 cells treated with isoproterenol. Therefore, 115h appears to be a novel
class of therapeutic for heart failure treatment.
PMID- 28699741
TI - Iron(II) Complexes of 2,4-Dipyrazolyl-1,3,5-triazine Derivatives-The Influence of
Ligand Geometry on Metal Ion Spin State.
AB - Seven [FeL2][BF4]2 complex salts were prepared, where L is a 6-substituted 2,4
di(pyrazol-1-yl)-1,3,5-triazine (bpt) derivative. The complexes are all
crystallographically high-spin, and exhibit significant distortions from an ideal
D2d-symmetric coordination geometry. In one case, an unusual type of metal ion
disorder was observed among a cubic array of ligands in the crystal lattice. The
complexes are also high-spin between 3 and 300 K in the solid state and, where
measured, between 239 and 333 K in CD3CN solution. This result is unexpected,
since homoleptic iron(II) complexes of related 2,6-di(pyrazol-1-yl)pyridine, 2,6
di(pyrazol-1-yl)pyrazine, and 2,6-di(pyrazol-1-yl)pyrimidine derivatives often
exhibit thermal spin-crossover behavior. Gas-phase density functional theory
calculations confirm the high-spin form of [Fe(bpt)2]2+ and its derivatives is
stabilized relative to iron(II) complexes of the other ligand types. This
reflects a weaker Fe/pyrazolyl sigma-bonding interaction, which we attribute to a
small narrowing of the chelate ligand bite angle associated with the geometry of
the 1,3,5-triazinyl ring. Hence, the high-spin state of [Fe(bpt)2]2+ centers does
not reflect the electronic properties of its heterocyclic ligand donors but is
imposed by the bpt ligand conformation. A high-spin homoleptic iron(III) complex
of one of the bpt derivatives was also synthesized.
PMID- 28699742
TI - Quantitative Analysis of Reactive Oxygen Species Photogenerated on Metal Oxide
Nanoparticles and Their Bacteria Toxicity: The Role of Superoxide Radicals.
AB - Ecotoxicity of engineered nanoparticles (NPs) has become the focus of
considerable attention because of their wide applications. Reactive oxygen
species (ROS) play important roles in the toxicity mechanisms of engineered metal
oxide NPs. This work aimed to understand quantitatively the contribution of
photogenerated ROS on metal oxide NPs to their toxicity. The dynamic generation
of O2*-, *OH, and H2O2 in aqueous suspensions of photoilluminated metal oxide
nano- and bulk particles (TiO2, ZnO, V2O5, CeO2, Fe2O3, and Al2O3) was measured
by a continuous-flow chemiluminescence (CFCL) detection system. Superoxides were
generated on all six nanoparticles as well as bulk TiO2 and ZnO, with nano TiO2
producing the highest concentration (180 nM). Hydroxyl radicals were detected on
both nano- and bulk TiO2 and ZnO, whereas H2O2 was detected only on TiO2 and ZnO
nanoparticles. The generation of ROS can in general be interpreted by the
electronic structures and surface defects of the NPs and the ROS redox
potentials. Furthermore, acute toxicity of the six metal oxide particles to a
luminescent bacterium, P. phosphoreum 502 was assessed after photoillumination.
The toxicity effect was attributed to the long-lived O2*- radicals on the
nanoparticlce, and its potency follows the order of TiO2 > ZnO > V2O5 > Fe2O3 >
CeO2 > Al2O3, which is the same as the order of the O2*- concentration measured
by CFCL. Our work revealed quantitatively the important role superoxide radicals
play in the toxicity of various metal oxide nanoparticles after
photoillumination.
PMID- 28699743
TI - Development and Validation of Quantitative Ultraperformance Liquid Chromatography
Tandem Mass Spectrometry Assay for Anticoagulant Rodenticides in Liver.
AB - Anticoagulant rodenticides (ARs) are used to control rodent populations; however,
exposure to nontarget animals occurs. A sensitive and rugged quantitative method
was developed, optimized, and validated for eight ARs in liver. Target analytes
comprised two chemical classes: hydroxycoumarins (warfarin, coumachlor,
dicoumarol, bromadiolone, brodifacoum, and difethialone) and indanediones
(diphacinone and chlorophacinone). In this method, liver extracts were cleaned
using dispersive solid phase extraction (d-SPE) to remove matrix interferences
and analyzed by reverse phase ultraperformance liquid chromatography-tandem mass
spectrometry (UPLC-MS/MS). Electrospray ionization in negative ion mode combined
with multiple reaction monitoring (MRM) using a triple quadrupole mass
spectrometer provided simultaneous confirmation and quantitation. Detection
limits spanned 0.75-25 ng/g, and lower quantitation limits were established as 50
ng/g. Interassay method accuracy ranged from 92 to 110% across the analytical
range (50-2500 ng/g) using matrix-matched calibrants with good repeatability
(relative standard deviations 2-16%). Successful method transfer to another
laboratory utilizing an Orbitrap mass analyzer, providing high mass accuracy, was
assessed by good method reproducibility during blinded study analyses (6-29%;
Horwitz ratios (HORRAT) <= 1.5).
PMID- 28699744
TI - Design, Synthesis, and Pharmacokinetics of a Bone-Targeting Dual-Action Prodrug
for the Treatment of Osteoporosis.
AB - A dual-action bone-targeting prodrug has been designed, synthesized, and
evaluated for in vitro and in vivo metabolic stability, in vivo tissue
distribution, and rates of release of the active constituents after binding to
bones through the use of differentially double-labeled derivatives. The conjugate
(general structure 7) embodies the merger of a very potent and proven anabolic
selective agonist of the prostaglandin EP4 receptor, compound 5, and alendronic
acid, a potent inhibitor of bone resorption, optimally linked through a
differentially hydrolyzable linker unit, N-4-carboxymethylphenyl
methyloxycarbonyl-leucinyl-argininyl-para-aminophenylmethylalcohol (Leu-Arg
PABA). Optimized conjugate 16 was designed so that esterase activity will
liberate 5 and cathepsin K cleavage of the Leu-Arg-PABA element will liberate
alendronic acid. Studies with doubly radiolabeled 16 provide a proof-of-concept
for the use of a cathepsin K cleavable peptide-linked conjugate for targeting of
bisphosphonate prodrugs to bone and slow release liberation of the active
constituents in vivo. Such conjugates are potential therapies for the treatment
of bone disorders such as osteoporosis.
PMID- 28699745
TI - Chiral Resolution of Lanthanoid Cryptates with Extreme Configurational Stability.
AB - Chiral resolution is achieved for racemic tris(2,2'-bipyridine)-based lanthanoid
cryptates by chiral HPLC. The resolved complexes exhibit very rare
configurational stability under extreme conditions.
PMID- 28699746
TI - Assignment of the Absolute Configuration of Phosphoeleganin via Synthesis of
Model Compounds.
AB - The full absolute configuration assignment of phosphoeleganin (1), a recently
discovered marine-derived phosphorylated polyketide with protein tyrosine
phosphatase 1B inhibitory activity, was achieved. It was based on the synthesis
of model diasteroisomeric compounds of the C-8-C-12 segment portion of
phosphoeleganin, chiral derivatization methods, and application of the universal
NMR database concept.
PMID- 28699747
TI - Pd(II)/Bipyridine-Catalyzed Conjugate Addition of Arylboronic Acids to alpha,beta
Unsaturated Carboxylic Acids. Synthesis of beta-Quaternary Carbons Substituted
Carboxylic Acids.
AB - Pd(II)/bipyridine-catalyzed conjugate addition of arylboronic acids to alpha,beta
unsaturated carboxylic acids (including beta,beta-disubstituted acrylic acids)
was developed and optimized, which provided a mild and convenient method for the
highly challenging synthesis of beta-quaternary carbons substituted carboxylic
acids.
PMID- 28699748
TI - Next Generation Hemostatic Materials Based on NHS-Ester Functionalized Poly(2
oxazoline)s.
AB - In order to prevent hemorrhage during surgical procedures, a wide range of
hemostatic agents have been developed. However, their efficacy is variable;
hemostatic devices that use bioactive components to accelerate coagulation are
dependent on natural sources, which limits reproducibility. Hybrid devices in
which chain-end reactive poly(ethylene glycol) is employed as active component
sometimes suffer from irregular cross-linking and dissolution of the polar PEG
when blood flow is substantial. Herein, we describe a synthetic, nonbioactive
hemostatic product by coating N-hydroxysuccinimide ester (NHS)-functional poly(2
oxazoline)s (POx-NHS) onto gelatin patches, which acts by formation of covalent
cross-links between polymer, host blood proteins, gelatin and tissue to seal the
wound site and prevent hemorrhage during surgery. We studied different process
parameters (including polymer, carrier, and coating technique) in direct
comparison with clinical products (Hemopatch and Tachosil) to obtain deeper
understanding of this class of hemostatic products. In this work, we successfully
prove the hemostatic efficacy of POx-NHS as polymer powders and coated patches
both in vitro and in vivo against Hemopatch and Tachosil, demonstrating that POx
NHS are excellent candidate polymers for the development of next generation
hemostatic patches.
PMID- 28699749
TI - Mechanistic Insight into Palladium-Catalyzed Cycloisomerization: A Combined
Experimental and Theoretical Study.
AB - The cycloisomerization of enynes catalyzed by Pd(OAc)2 and bis-benzylidene
ethylenediamine (bbeda) is a landmark methodology in transition-metal-catalyzed
cycloisomerization. However, the mechanistic pathway by which this reaction
proceeds has remained unclear for several decades. Here we describe mechanistic
investigations into this reaction using enynamides, which deliver azacycles with
high regio- and stereocontrol. Extensive 1H NMR spectroscopic studies and isotope
effects support a palladium(II) hydride-mediated pathway and reveal crucial roles
of bbeda, water, and the precise nature of the Pd(OAc)2 pre-catalyst.
Computational studies support these mechanistic findings and lead to a clear
picture of the origins of the high stereocontrol that can be achieved in this
transformation, as well as suggesting a novel mechanism by which hydrometalation
proceeds.
PMID- 28699751
TI - Improvement of Green Upconversion Monochromaticity by Doping Eu3+ in
Lu2O3:Yb3+/Ho3+ Powders with Detailed Investigation of the Energy Transfer
Mechanism.
AB - The monochromaticity improvement of green upconversion (UC) in Lu2O3:Yb3+/Ho3+
powders has been successfully realized by tridoping Eu3+. The integral area ratio
of green emission to red emission of Ho3+ increases 4.3 times with increasing
Eu3+ doping concentration from 0 to 20 mol %. The energy transfer (ET) mechanism
in the Yb3+/Ho3+/Eu3+ tridoping system has been investigated carefully by visible
and near-infrared (NIR) emission spectra along with the decay curves, revealing
the existence of ET from the Ho3+5F4/5S2 level tothe Eu3+5D0 level and ET from
the Ho3+5I6 level to the Eu3+7F6 level. In addition, the population routes of the
red-emitting Ho3+5F5 level in the Yb3+/Ho3+ codoped system under 980 nm
wavelength excitation have also been explored. The ET process from the Yb3+2F5/2
level to the Ho3+5I7 level and the cross-relaxation process between two nearby
Ho3+ ions in the 5F4/5S2 level and 5I7 level, respectively, have been
demonstrated to be the dominant approaches for populating the Ho3+5F5 level. The
multiphonon relaxation process originating from the Ho3+5F4/5S2 level is useless
to populate the Ho3+5F5 level. As the energy level gap between the Ho3+5I7 level
and Ho3+5I8 level matches well with that between Eu3+7F6 level and Eu3+7F0 level,
the energy of the Ho3+5I7 level can be easily transferred to the Eu3+7F6 level by
an approximate resonant ET process, resulting in a serious decrease in the red UC
emission intensity. Since this ET process is more efficient than the ET from the
Ho3+5F4/5S2 level to the Eu3+5D0 level as well as the ET from the Ho3+5I6 level
to the Eu3+7F6 level, the integral area ratio of green emission to red emission
of Ho3+ has been improved significantly.
PMID- 28699752
TI - Structural Distortion, Spin-Phonon Coupling, Interband Electronic Transition, and
Enhanced Magnetization in Rare-Earth-Substituted Bismuth Ferrite.
AB - Rare-earth ions (RE = La3+, Nd3+, and Er3+) substituted BiFeO3 (BFO) ceramics
were synthesized by a conventional solid-state sintering procedure. X-ray
diffraction patterns and Raman spectra confirm a rhombohedral R3c symmetry in all
samples with significant distortion in FeO6 octahedron, as well as the occurrence
of remarkable spin-phonon coupling and notable change in magnetic transition
temperature induced by RE dopants. The enhanced magnetization was observed in all
RE-doped BFO ceramics, unveiling that the spatial spin structure of BFO should be
perturbed by RE dopants. Diffuse reflectance spectra show a conspicuous evolution
of interband electronic transitions in RE-doped BFO ceramics. Especially, the two
crystal-field d-d band transitions (6A1g->4T1 and 6A1g->4T2g) exhibit a linear
red-shift behavior with the reduction in the cell volume, which is well-linked
with a linear tendency of increased magnetization. On the basis of these
investigations, a possible mechanism was proposed in this paper to demonstrate
the correlation between the structural distortion, interband electronic
transitions, and magnetic properties in RE-doped BFO ceramics.
PMID- 28699753
TI - Identification of Anthocyanins from Four Kinds of Berries and Their Inhibition
Activity to alpha-Glycosidase and Protein Tyrosine Phosphatase 1B by HPLC-FT-ICR
MS/MS.
AB - The polyphenolic profiles of four berries (blueberry, bilberry, mulberry, and
cranberry) in China were investigated using Fourier transform-ion cyclotron
resonance mass spectrometry (FT-ICR MS). Thirty-nine polyphenols including 26
anthocyanins, 9 flavonoids, and 4 phenolic acids were identified accurately.
Cyanidin aglycones are common in four berries, and malvidin aglycones are the
main compounds found in bilberry and cranberry. The anthocyanin level in
blueberry are the highest with 739.6 +/- 17.14 mg/g DW and presented the
strongest antioxidant capacity in DPPH, ABTS, FRAP, and ORAC assay. In alpha
glycosidase, the inhibition activity was in the following order: mulberry >
bilberry > blueberry > cranberry. For the PTP1B inhibition assay, blueberry
demonstrated the highest inhibitory effect with IC50 3.06 +/- 0.02 MUg/mL,
followed by bilberry, mulberry, and cranberry. Molecular docking results showed
that cyanidin aglycones had the highest inhibition activity to PTP1B.
PMID- 28699750
TI - Chemistry and Enzymology of Disulfide Cross-Linking in Proteins.
AB - Cysteine thiols are among the most reactive functional groups in proteins, and
their pairing in disulfide linkages is a common post-translational modification
in proteins entering the secretory pathway. This modest amino acid alteration,
the mere removal of a pair of hydrogen atoms from juxtaposed cysteine residues,
contrasts with the substantial changes that characterize most other post
translational reactions. However, the wide variety of proteins that contain
disulfides, the profound impact of cross-linking on the behavior of the protein
polymer, the numerous and diverse players in intracellular pathways for disulfide
formation, and the distinct biological settings in which disulfide bond formation
can take place belie the simplicity of the process. Here we lay the groundwork
for appreciating the mechanisms and consequences of disulfide bond formation in
vivo by reviewing chemical principles underlying cysteine pairing and oxidation.
We then show how enzymes tune redox-active cofactors and recruit oxidants to
improve the specificity and efficiency of disulfide formation. Finally, we
discuss disulfide bond formation in a cellular context and identify important
principles that contribute to productive thiol oxidation in complex, crowded,
dynamic environments.
PMID- 28699754
TI - Diastereo- and Enantioselective Synthesis of 2,2-Disubstituted Benzofuran-3-one
Bearing Adjacent Quaternary and Tertiary Stereocenters.
AB - The first highly diastereo- and enantioselective synthesis of armeniaspirol
analogues was achieved using L-proline derived bifunctional squaramide which
outperformed commonly used organocatalysts. Excellent yield (up to 99%) with
diastereoselectivity (up to 99:1) and enantioselectivity (up to 99%) were
obtained for a wide range of substrates.
PMID- 28699755
TI - CO2-Reactive Ionic Liquid Surfactants for the Control of Colloidal Morphology.
AB - This article reports on a new class of stimuli-responsive surfactant generated
from commercially available amphiphiles such as dodecyltrimethylammmonium bromide
(DTAB) by substitution of the halide counterion with counterions such as 2
cyanopyrrolide, 1,2,3-triazolide, and L-proline that complex reversibly with CO2.
Through a combination of small-angle neutron scattering (SANS), electrical
conductivity measurements, thermal gravimetric analysis, and molecular dynamics
simulations, we show how small changes in charge reorganization and counterion
shape and size induced by complexation with CO2 allow for fine-tunability of
surfactant properties. We then use these findings to demonstrate a range of
potential practical uses, from manipulating microemulsion droplet morphology to
controlling micellar and vesicular aggregation. In particular, we focus on the
binding of these surfactants to DNA and the reversible compaction of surfactant
DNA complexes upon alternate bubbling of the solution with CO2 and N2.
PMID- 28699756
TI - Incorporation of a Biguanide Scaffold Enhances Drug Uptake by Organic Cation
Transporters 1 and 2.
AB - Membrane transporters play a significant role in the transport of many endogenous
and exogenous compounds. The knowledge of transporter substrate requirements has
allowed further development of drugs that utilize them to ensure tissue
permeation. In this study, we demonstrate that inclusion of a biguanide
functionality can potentiate uptake by the organic cation transporters 1 and 2
(OCT1 and OCT2). We synthesized 18 pairs of structurally diverse compounds, each
pair consisting of a parent amino compound and its biguanide analog; and then
assessed their cellular uptake in HEK293 cells overexpressing human OCT1 or OCT2.
Our results show that addition of the biguanide significantly improved OCT1- and
OCT2-mediated transport for the majority of compounds. The biguanides also
inhibited the uptake of prototypical substrates of both transporters, 1-methyl-4
phenylpyridinium (MPP+) and metformin. We found that molecular weight, molecular
volume, Log D (pH 7.4), and accessible surface area were important determinants
of OCT2 substrates, but none of these parameters was a significant factor for
OCT1. More so, the inhibition of MPP+ uptake correlated linearly with that of
metformin uptake for the tested biguanides in both cell lines. Taken together, we
conclude that the inclusion of the biguanide scaffold in nonsubstrates of OCT1
and OCT2 increase their propensity to become substrates and inhibitors for these
transporters.
PMID- 28699757
TI - Solvent-Driven Dynamical Crossover in the Phenylalanine Side-Chain from the
Hydrophobic Core of Amyloid Fibrils Detected by 2H NMR Relaxation.
AB - Aromatic residues are important markers of dynamical changes in proteins'
hydrophobic cores. In this work we investigated the dynamics of the F19 side
chain in the core of amyloid fibrils across a wide temperature range of 300 to
140 K. We utilized solid-state 2H NMR relaxation to demonstrate the presence of a
solvent-driven dynamical crossover between different motional regimes, often also
referred to as the dynamical transition. In particular, the dynamics are
dominated by small-angle fluctuations at low temperatures and by pi-flips of the
aromatic ring at high temperatures. The crossover temperature is more than 43
degrees lower for the hydrated state of the fibrils compared to the dry state,
indicating that interactions with water facilitate pi-flips. Further, crossover
temperatures are shown to be very sensitive to polymorphic states of the fibrils,
such as the 2-fold and 3-fold symmetric morphologies of the wild-type protein as
well as D23N mutant protofibrils. We speculate that these differences can be
attributed, at least partially, to enhanced interactions with water in the 3-fold
polymorph, which has been shown to have a water-accessible cavity. Combined with
previous studies of methyl group dynamics, the results highlight the presence of
multiple dynamics modes in the core of the fibrils, which was originally believed
to be quite rigid.
PMID- 28699758
TI - Resilience of Malic Acid Natural Deep Eutectic Solvent Nanostructure to
Solidification and Hydration.
AB - Little is presently known about the unique nanostructure of deep eutectic
solvents (DES). The order of the liquid-solid phase transition is contended and
whether DES-water mixtures are merely aqueous solutions, or have properties
dominated by the eutectic pair, is unclear. Here, we unambiguously show the
structure of choline chloride-malic acid (malicine) as a liquid, and also in
solid and hydrated forms, using neutron total scattering on D/H isotope
substituted samples, and quasi-elastic neutron scattering (QENS). Data were
refined using empirical potential structure refinement. We show evidence for a
stoichiometric complex ion cluster in the disordered liquid, with strong choline
chloride bonding and a hydrogen bond donor (HBD) contribution. The 1:1 eutectic
stoichiometry makes these ionic domains more well-defined, with less HBD
clustering than seen previously for reline. There is minimal structural
difference for the solidified material, demonstrating that this DES
solidification is a glass transition rather than a first order phase change. QENS
data support this by showing a gradual change in solvent dynamics rather than a
step change. The DES structure is mostly retained upon hydration, with water
acting both as a secondary smaller HBD at closer range to choline than malic
acid, and forming transient wormlike aggregates. This new understanding of DES
structure will aid understanding of the properties of these novel green solvents
on the molecular length scale in chemical processes, as well as giving an insight
into the apparent role of natural DESs in plant physiology.
PMID- 28699759
TI - Ethynylene-linked Figure-Eight Octaphyrin(1.2.1.1.1.2.1.1): Synthesis and
Characterization of Its Two Oxidation States.
AB - An octaphyrin(1.2.1.1.1.2.1.1) containing two conjugated ethynylene bridges has
been synthesized and characterized. The macrocycle reveals complex conformational
dynamics dependent on its protonation and oxidation state. The [40]annulenoid
macrocycle and its [38]annulenoid oxidized form display residual macrocyclic ring
currents. In spite of its low apparent aromaticity the new octaphyrin is a potent
chromophore with a vis-NIR absorption profile strongly influenced by the redox
and acid-base chemistry.
PMID- 28699760
TI - Preparation of Quinazolines via a 2+2+2 Annulation from Aryldiazonium Salts and
Nitriles.
AB - A (2+2+2) modular synthesis of multisubstituted quinazolines has been realized by
the direct reaction of aryldiazonium salts with two equivalent of nitriles.
Reaction of aryldiazonium salt with a nitrile provides the initial formation of a
reactive nitrilium ion, which is attacked by another molecule of nitrile followed
by electrophilic cyclization to deliver the desired product. Notable flexibility
in the substitution patterns, readily available substrates, short reaction time,
transition metal-free, and gram-scale synthesis are the advantages of this
method.
PMID- 28699761
TI - Comparison of Intermolecular Forces in Anhydrous Sorbitol and Solvent Cocrystals.
AB - The hygroscopicity of solid sorbitol is important for its utilization as a
sweetener in the pharmaceutical and food industries. The molecular foundations of
sorbitol hydration characteristics are explored here using two solvated
cocrystals, sorbitol-water and sorbitol-pyridine. In this work, solid-state
density functional theory and terahertz time-domain spectroscopy were used to
evaluate the relative stabilities of these cocrystals as compared to anhydrous
sorbitol in terms of conformational and cohesive energies. The modification of
the hydrogen-bonding network in crystalline sorbitol by solvent molecules gives
new insight into the origins of the notable stability of sorbitol-water as
compared to similar solids such as mannitol-water. In particular, the energy
analysis reveals that the relative instability of the mannitol hydrate is based
primarily in the lack of water-water interactions which provide considerable
stabilization in the sorbitol-water crystal.
PMID- 28699762
TI - Coloring by Number? Core Outcome Measures and the Canvas of Intensive Care Unit
Survivorship.
PMID- 28699763
TI - Severity Scores and Community-acquired Pneumonia. Time to Move Forward.
PMID- 28699764
TI - Correction to Dose specification for hippocampal sparing whole brain radiotherapy
(HS WBRT): considerations from the UK HIPPO trial QA programme.
PMID- 28699765
TI - Fetal Alcohol Syndrome Disorder: diminished responsibility and mitigation of
sentence.
AB - OBJECTIVE: The objective of this study was to consider the implications of a
recent Western Australia Court of Appeal decision in which an indigenous youth
who had been sentenced for the manslaughter of his neonate child was later
diagnosed with Fetal Alcohol Syndrome Disorder. CONCLUSION: The increased use of
the 2016 Australian guide to the diagnosis of fetal alcohol spectrum disorder
should be encouraged to enable clinicians to not only diagnose and manage Fetal
Alcohol Syndrome Disorder, but also counsel families to prevent it.
PMID- 28699766
TI - Assessing acute psychological distress in the immediate aftermath of stroke.
AB - BACKGROUND AND PURPOSE: High acute stress may presage the development of
subsequent cardiovascular ailments. Understanding how best to assess acute stress
may inform early interventions seeking to prevent long-term morbidity/mortality
following stroke. A mixed methods approach examined early post-stroke acute
stress symptoms using the post-traumatic stress disorder checklist-5 (PCL-5) and
the acute stress disorder scale (ASDS). METHODS: A focus group of stroke
survivors and/or their caregivers ( N=8) evaluated PCL-5/ASDS feasibility, and 20
patients hospitalized for acute stroke were interviewed 2-10 days post-stroke
onset, using either the PCL-5 or the ASDS. RESULTS: Acute stress symptoms were
present and measurable during acute stroke recovery. Assessment of acute stress
in hospitalized patients with stroke is feasible; a briefer modified ASDS has
advantages over the PCL-5. CONCLUSIONS: The ASDS is a viable and useful measure
for assessing psychological distress during the acute post-stroke aftermath.
Findings suggest that acute stress symptoms are present among patients with
stroke, warranting greater attention to psychological responses in the early post
stroke period. Given that acute stress has serious potential long-term health
consequences, additional research on stroke-related acute stress may prove useful
for understanding post-stroke morbidity/mortality.
PMID- 28699768
TI - ST37 Klebsiella pneumoniae: development of carbapenem resistance in vivo during
antimicrobial therapy in neonates.
AB - AIM: To investigate the mechanism leading to in vivo carbapenem resistance
development in Klebsiella pneumoniae. METHODS: Carbapenemase was detected using
the modified carbapenem inactivation method. beta-lactamases resistant genes were
identified by PCR and sequencing. Clonal relatedness was evaluated by random
amplified polymorphic DNA and multiple locus sequence typing. The relationship
between sequence typing and resistant genes was analyzed by using the chi-squared
test. RESULTS: All ST37 carbapenem-resistant isolates were blaOXA-1 positive and
all ST37 carbapenem-sensitive isolates were blaOXA-1 negative at Stage I. A
significant relationship between carbapenem resistance and blaOXA-1 was observed.
The blaOXA-1 -positive rate was significantly higher in ST37 K. pneumoniae than
others. CONCLUSION: This is the first study about the development of carbapenem
resistance in vivo potentially mediated by blaOXA-1 in ST37 K. pneumoniae among
neonates.
PMID- 28699769
TI - Deriving more value from RWE to ensure timely access of medicines by patients.
PMID- 28699770
TI - Sex differences in health status and rehabilitation outcomes in patients with
atrial fibrillation treated with ablation: Results from the CopenHeartRFA trial.
AB - BACKGROUND: Increased physical capacity after comprehensive rehabilitation in
patients with atrial fibrillation (AF) undergoing ablation has been found in the
CopenHeartRFA trial. The purpose of this study was to investigate: (a) sex
differences in health status, psychological distress and quality of life, (b) sex
differences in rehabilitation outcomes and (c) predictors of effect of
rehabilitation. METHODS: We conducted an exploratory analysis of data from the
randomized CopenHeartRFA trial, where patients treated with ablation were
randomized with 1:1 to comprehensive rehabilitation consisting of a physical
exercise program and psycho-educational consultations versus usual care. Sex
disparities in health status were tested using Chi-square and t-tests. RESULTS:
Included were: 151 men (median age 59.25 years) and 59 women (median age 62.5
years). At hospital discharge, women reported lower physical health status
compared with men. Among women, significant differences were found in the 6-min
walk test [rehabilitation: 496.8 meters (SD 98.5) versus 559.3meters (SD 55.5)
and usual care: 521.9 meters (SD 97.8) versus 530.9 meters (SD 102.2), p = 0.01]
and exercise time [rehabilitation: 387.6 s (SD 126.0) versus 463.2 s (SD 121.8)
and usual care: 353.4 s (SD 145.2) versus 355.8 s (SD 154.8), p < 0.004] and
among men in the sit-to-stand test. Significant differences were found in mental
health outcomes among men and in quality of life scores among women. Patients
with a European Heart Rhythm Association (EHRA) score I-II had a positive effect
of rehabilitation. CONCLUSION: The results suggest that sex differences exist in
self-reported health after rehabilitation in patients ablated for AF. Patients
with an I-II EHRA score seem more likely to gain from the rehabilitation
programme compared with those with a III-IV score.
PMID- 28699771
TI - Comparative effectiveness of surgery versus antibiotics in acute appendicitis: a
systematic review.
AB - AIM: To review outcomes of surgical and antibiotic management of acute
appendicitis. METHODS: 11 prospective studies comparing surgical versus
antibiotic management of acute appendicitis over a 21-year period were reviewed.
RESULTS: Antibiotic management is successful in most cases of uncomplicated acute
appendicitis. The need for crossover in management and recurrent appendicitis
were low among all studies. For those patients who ultimately required surgery,
no increased complications were observed. CONCLUSION: The decision to use
antibiotics to treat acute appendicitis should be held to the same standards of
diagnostic rigor as surgical management. Antibiotics may be safely recommended in
patients with high surgical risk, such as the elderly or those with multiple
comorbidities.
PMID- 28699772
TI - Incorporating cardiopulmonary resuscitation training into a cardiac
rehabilitation programme: A feasibility study.
AB - BACKGROUND: Patients with a cardiac history are at future risk of cardiac events,
including out-of-hospital cardiac arrest. Targeting cardiopulmonary resuscitation
(CPR) training to family members of cardiac patients has long been advocated, but
is an area in need of contemporary research evidence. An environment yet to be
investigated for targeted training is cardiac rehabilitation. AIM: To evaluate
the feasibility of providing CPR training in a cardiac rehabilitation programme
among patients, their family members and staff. METHODS: A prospective before and
after study design was used. CPR training was delivered using video self
instruction CPR training kits, facilitated by a cardiac nurse. Data was collected
pre-training, post-training and at one month. RESULTS: Cardiac patient
participation rates in CPR classes were high ( n = 56, 72.7% of eligible
patients) with a further 27 family members attending training. Patients were
predominantly male (60.2%), family members were predominantly female (81.5%),
both with a mean age of 65 years. Confidence to perform CPR and willingness to
use skills significantly increased post-training (both p<0.001). Post training
participants demonstrated a mean compression rate of 112 beats/min and a mean
depth of 48 mm. Training reach was doubled as participants shared the video self
instruction kit with a further 87 people. Patients, family members and cardiac
rehabilitation staff had positive feedback about the training. CONCLUSIONS: We
demonstrated that cardiac rehabilitation is an effective and feasible environment
to provide CPR training. Using video self-instruction CPR training kits enabled
further training reach to the target population.
PMID- 28699773
TI - Variability amongst urine toxicology amphetamine readings with concurrent
administration of fenofibrate.
AB - OBJECTIVE: The aim of this study was to highlight that concurrent administration
of the common lipid-lowering agent fenofibrate may lead to false-positive
amphetamine results in often-used immunoassay-based urine drug screens. It also
aimed to show that there are significant moral and clinical challenges associated
with the interpretation of such results amongst psychiatric inpatients.
CONCLUSIONS: It is evident that different pathology laboratories may utilise
different commercial urine drug-screen immunoassays in their toxicology analysis,
with variability in the test specificities. Despite the relatively high
prevalence of substance misuse in the population of psychiatric inpatients, there
exists a need for increased vigilance towards the possibility of false-positive
amphetamine results owing to likely cross-reactivity of fenofibrate with the test
reagents. In cases where there is uncertainty when correlating clinically, or
where false positives are suspected, gold-standard urine-sample analysis by mass
spectrometry should be considered, particularly when the consequences for
patients may include restrictive measures.
PMID- 28699774
TI - Genomic heterogeneity: next-generation sequencing enables biomarker
identification for hepatocellular carcinoma.
PMID- 28699775
TI - Assessing antibiotic therapy effectiveness against the major bacterial pathogens
in a hospital using an integrated index.
AB - AIM: To assess the effectiveness of antibiotic therapy against five indicator
bacteria in a Chinese hospital using an index-based approach. METHODS: The study
population comprises 1031 patients who had one clinically significant bacterial
isolate in 2008, 2010 and 2013. Drug resistance index (DRI) based on pathogens
was calculated. RESULTS: The adaptive DRIs for Klebsiella pneumoniae, Pseudomonas
aeruginosa, Staphylococcus aureus decreased, while both adaptive and fixed DRIs
for Acinetobacter spp. increased from 2008 to 2013. The adaptive DRIs for
Escherichia coli increased from 2008 to 2013, while the fixed DRIs exhibited a
decreasing trend. CONCLUSION: DRI could be used to demonstrate the changes of
antimicrobial resistance and prescribing over time as a result of evolutionary
processes and governmental regulatory interference.
PMID- 28699776
TI - Divided we fall: clinicians and academic psychiatrists need to stand together.
AB - OBJECTIVE: Psychiatry faces urgent problems requiring united action. These
problems affect academic psychiatrists in the universities, and clinicians in
publicly funded mental health services. Academic units are isolated and
endangered, finding it difficult to recruit. They could benefit from closer
relationships with public mental health services, in terms of recruitment, shared
teaching and clinical research. However, mental health services are preoccupied
with their own problems, particularly in relation to acute clinical demand. How
can we stand together to improve academic units and clinical psychiatry?
CONCLUSIONS: Clinicians and academic psychiatrists can stand together on
important matters, but it takes initiatives from local leaders to overcome the
structural barriers between health services and the universities. An example is
given of united action by clinicians and academic psychiatrists to address a
crisis within a state mental health system. First, psychiatrists undertook
independent health services research that compared the state system with those in
other Australian and international jurisdictions. The comparative data was used
to generate solutions, which were presented at every level from ministerial
offices through to service managers. Finally, psychiatrists took up joint
academic and clinical leadership roles in the university and the mental health
system. This united research-led approach turned around the crisis in the state
mental health system.
PMID- 28699777
TI - Caring for an individual with mild cognitive impairment: a qualitative
perspective of health-related quality of life from caregivers.
AB - OBJECTIVES: Little is known regarding the effect that caring for an individual
with Mild Cognitive Impairment (MCI) has on health-related quality of life
(HRQOL). We sought to identify the most important aspects of HRQOL related to
caring for an individual with MCI. METHODS: Six focus groups were conducted with
caregivers of individuals with MCI (n = 32). Qualitative frequency analysis was
used to analyze the data. RESULTS: Findings indicated that caregivers most
frequently discussed social health, including changes in social roles and an
increased need for social support (51.2% of the total discussion). This was
followed by mental health concerns (37.9%) centering on anger/frustration, and a
need for patience in the caregiving role, as well as caregiver-specific anxiety.
Other topics included physical health (10.0%; including the impact that stress
and burden have on medical heath), and caregivers' cognitive health (0.9%;
including memory problems in relation to caregiver strain, sleep disruption, and
cognitive fatigue). CONCLUSIONS: Findings illustrate the multiple domains of
HRQOL that are affected in individuals providing care for someone with MCI.
Moreover, the findings highlight the need for extending support services to MCI
caregivers, a group that is typically not offered support services due to the
'less severe' nature of an MCI diagnosis.
PMID- 28699778
TI - Neurofeedback as an adjunct therapy for treatment of chronic posttraumatic stress
disorder related to refugee trauma and torture experiences: two case studies.
AB - OBJECTIVE: The objective of this study was to describe the use of neurofeedback
for refugee-related chronic posttraumatic stress disorder (PTSD) in two case
studies. METHODS: We describe the assessment and application of neurofeedback
integrated into the treatment of two clients with chronic PTSD. We include
details of our treatment schedule, symptoms and quantitative electrophysiological
data for each case. Results All clients achieved significant reduction in
symptoms of PTSD and improvement in daily functioning post-neurofeedback therapy.
Quantitative electroencephalogric (EEG) measures indicate a normalisation of EEG
markers relating to trauma, including overarousal at rest and working memory
function. Conclusions Neurofeedback as an adjunct to trauma-informed therapy may
help to remediate chronic PTSD relating to refugee experiences. If replicated
then improvements demonstrated in this population would be generalisable to all
chronic PTSD.
PMID- 28699779
TI - Indication-specific pricing of pharmaceuticals in the US healthcare system.
AB - AIM: To explore the potential of indication-specific pricing (ISP) of
pharmaceuticals and to discuss prospects for implementation in the US healthcare
system. MATERIALS & METHODS: The Institute for Clinical and Economic Review
convened a policy forum with 44 healthcare leaders from 22 payer and life
sciences companies. Models of ISP were discussed. RESULTS: Payers and drug
manufacturers saw the potential benefits of an ISP system that balances
affordability for payers, sustainability for manufacturers and access for
patients. The US healthcare system presents many challenges to implementation,
including potential conflicts with existing pricing policies (Medicaid Best
Price, average sales price and 340B) and insufficient data systems and analytic
capabilities. CONCLUSION: Possible solutions and policy recommendations for
payers and manufacturers are provided.
PMID- 28699780
TI - Depression, anxiety and stress severities in multiple sclerosis patients using
injectable versus oral treatments.
AB - AIM: Studies on multiple sclerosis in Saudi Arabia remain scant, particularly
studies on the psychological aspects. This study measures severities of
depression, anxiety and stress, and compares them to the used disease-modifying
treatment. MATERIALS & METHODS: Cross-sectional study using a phone questionnaire
targeting 452 Saudi patients with relapsing-remitting multiple sclerosis
following in King Khalid University Hospital, King Fahad Medical City or Security
Forces Hospital. RESULTS: From 235 patients, 149 used interferons, 58 used
fingolimod and 28 used natalizumab. Depression scores were similar among all
demographic and drug groups. Interferons versus fingolimod anxiety scores were
significantly different (p = 0.035). Stress scores were within normal limits.
CONCLUSION: Mild anxiety was higher among interferon users, which could be due to
injection anxiety reasons.
PMID- 28699781
TI - Application of Bacillus megaterium MCR-8 improved phytoextraction and stress
alleviation of nickel in Vinca rosea.
AB - The current research was performed to evaluate the effect of Bacillus megaterium
MCR-8 on mitigation of nickel (Ni) stress in Vinca rosea grown on Ni-contaminated
soil (50, 100, and 200 mg Ni kg-1 soil). The treated plants exhibited reduced
growth, biomass, gas exchange capacity, and chlorophyll (Chl) content under Ni
stress. The inoculated plants growing in Ni-contaminated media exhibited
relatively higher growth, total soluble protein, and proline contents. Similarly,
bacterial inoculation improved the activity of antioxidant enzymes including
superoxide dismutase (SOD), catalase (CAT), peroxidase (POD), and ascorbate
peroxidase (APX) under Ni stress. The Ni stress alleviation in inoculated plants
was attributed to the reduced level of malondialdehyde (MDA) and hydrogen
peroxide (H2O2), enhanced synthesis of protein, proline, phenols, and flavonides
in conjunction with improved activity of antioxidant enzymes. The growth
promoting characteristics of microbe such as 1-aminocyclopropane-1-carboxylate
deaminase (ACCD) and phosphate solubilization activity, siderophore, and auxin
production capability also improved the growth and stress mitigation in
inoculated plants. Furthermore, the inoculated plants exhibited higher value for
bioconcentration factor (BCF), translocation factor (TF), and resulted in higher
loss of Ni content from soil. The current results exhibited the beneficial role
of B. megaterium MCR-8 regarding stress alleviation and Ni phytoextraction by V.
rosea.
PMID- 28699782
TI - Bacterial siderophores promote plant growth: Screening of catechol and
hydroxamate siderophores.
AB - The aim of the study was to determine the quality and quantity of siderophores
produced by bacteria isolated from plants' roots. The second aim was to determine
the effect of siderophores on plants growth (Festuca rubra L. and Brassica napus
L.). The study was carried out using bacteria isolated from roots of: Arabidopsis
thaliana L., F. rubra, and Agrostis capillaris L., growing on the heavy metals
contaminated area. The chrome azurol sulfonate (CAS) test, Arnow's test for
catechol siderophores, and Csaksy's test for hydroxamate siderophores were
performed. Among the bacteria, 42 isolates (39%) had a positive result in the
CAS. Endophytic bacteria were mostly producing the catechol siderophores. It was
found that F. rubra is the plant which is linked with the highest number of
siderophores producing bacteria. The highest concentration of siderophores was
noted for ectorhizospheric bacteria associated with A. thaliana,
hyperaccumulating plant. It was found that hydroxamate siderophores are mainly
produced by ectorhizosphere and rhizoplane bacteria. The siderophores producing
bacteria reduced the toxicity of metals and improved the phytoremediation.
Siderophores treatment increased the growth of plants in the biological assay,
growing on two different soils: one highly contaminated with heavy metals and the
second strongly alkaline soil.
PMID- 28699783
TI - Phytoremediation of organochlorine pesticides: Concept, method, and recent
developments.
AB - Rapid increase in industrialization of world economy in the past century has
resulted in significantly high emission of anthropogenic chemicals in the
ecosystem. The organochlorine pesticides (OCPs) are a great risk to the global
environment and endanger the human health due to their affinity for dispersion,
transportation over long distances, and bioaccumulation in the food chain.
Phytoremediation is a promising technology that aims to make use of plants and
associated bacteria for the treatment of groundwater and soil polluted by these
contaminants. Processes known to be involved in phytoremediation of OCPs include
phytoaccumulation, rhizoremediation, and phytotransformation. Vegetation has been
accounted to considerably amplify OCP elimination from soil, in contrast to non
planted soil, attributable to both, uptake within plant tissues and high
microbial degradation of OCP within the root zone. Developing transgenic plants
is a promising approach to enhance phytoremediation capabilities. Recent advances
in the application of phytoremediation technique for OCPs, including uptake by
plants and plant-microbe association in the rhizosphere for the enhanced
degradation and mineralization of these pollutants, is presented in this review.
Additionally, some attempts to improve this technique using transgenesis and role
of certain enzymes are also discussed.
PMID- 28699784
TI - Cancer drugs and QT prolongation: weighing risk against benefit.
PMID- 28699785
TI - Assessment of Meat and Poultry Product Recalls Due to Salmonella Contamination:
Product Recovery and Illness Prevention.
AB - Data from the recalls of meat and poultry products from 2000 through 2012 due to
Salmonella contamination were used to assess the factors associated with the
recovery of the recalled product and to develop quantitative models to estimate
the number of illnesses prevented by recalls. The percentage of product recovered
following a recall action was not dependent on establishment size, recall
expansions, complexity of the distribution chain, type of distribution, amount of
time between the production and recall dates, or number of pounds of product
recalled. However, illness-related recalls were associated with larger amounts of
recalled product, smaller percentages of recalled product recovered, a greater
number of days between the production date and recall date, and nationwide
distribution than were recalls that were not illness related. In addition, the
detection of recall-associated illnesses appeared to be enhanced in states with
strong foodborne illness investigation systems. The number of Salmonella
illnesses prevented by recalls was based on the number of illnesses occurring
relative to the number of pounds consumed, which was then extrapolated to the
number of pounds of recalled product recovered. A simulation using a program
evaluation and review technique probability distribution with illness-related
recalls from 2003 through 2012 estimated that there were 19,000 prevented
Salmonella illnesses, after adjusting for underdiagnosis. Recalls not associated
with illnesses from 2000 through 2012 prevented an estimated additional 8,300
Salmonella illnesses, after adjusting for underdiagnosis. Although further
improvements to ensure accurate and complete reporting should be undertaken, our
study demonstrates that recalls are an important tool for preventing additional
Salmonella illnesses. Moreover, additional training resources dedicated to public
health agencies for enhancing foodborne illness detection, investigations, and
rapid response and reporting would further prevent illnesses.
PMID- 28699786
TI - Inactivation of Norovirus by Lemongrass Essential Oil Using a Norovirus Surrogate
System.
AB - This study investigated the effect of lemongrass essential oil (LGEO) on the
infectivity and viral replication of norovirus. Murine norovirus 1 (MNV-1), a
surrogate of human norovirus, was preincubated with LGEO and then used to infect
RAW 264.7 cells in a plaque reduction assay. LGEO exhibited a significant
reduction in MNV-1 plaque formation in both time- and dose-dependent manners. The
quantification of viral genome by quantitative real-time PCR showed similar
results in line with those of the plaque reduction assay. It was revealed that
citral, a single compound in LGEO, showed dramatic reduction in MNV-1 infectivity
(-73.09% when using a treatment of 0.02%, v/v). The inhibitory activity of LGEO
on viral replication was further investigated in HG23 cells that harbored a human
norovirus replicon. LGEO treatment significantly reduced viral replication in
HG23 cells, which suggests that LGEO may have dual inhibitory activities that
inactivate viral coat proteins required for viral infection and suppress
norovirus genome replication in host cells. In animal experiments, oral
administration of murine norovirus preincubated with LGEO significantly
suppressed virus infectivity in vivo. Collectively, these results suggest that
LGEO, in particular the LGEO component citral, inactivates the norovirus and its
subsequent replication in host cells. Thus, LGEO shows promise as a method of
inhibiting norovirus within the food industry.
PMID- 28699787
TI - Erratum.
PMID- 28699788
TI - Allogeneic cell therapy manufacturing: process development technologies and
facility design options.
AB - INTRODUCTION: Currently, promising outcomes from clinical trials of allogeneic
cells, especially allogeneic mesenchymal stromal cells, fibroblasts,
keratinocytes, and human cardiac stem cells, have encouraged research
institutions, small and medium enterprises (SMEs), and big pharmaceutical
companies to invest and focus on developing allogeneic cell therapy products.
Commercial and large-scale production of allogeneic cell therapy products
requires unique capabilities to develop technologies that generate safe and
effective allogeneic cells/cell lines and their fully characterized
master/working banks. In addition, it is necessary to design robust upstream and
downstream manufacturing processes, and establish integrated, well-designed
manufacturing facilities to produce high quality affordable products in
accordance with current GMP regulations for the production of cell therapy
products. Areas covered: The authors highlight: the recent advances in the
development of allogeneic products, the available options to develop robust
manufacturing processes, and facility design considerations. Expert opinion:
Currently, there are multiple challenges in development of allogeneic cell
therapy products. Indeed, the field is still in its infancy; with technologies
and regulations still under development, as is our understanding of the
mechanisms of action in the body and their interaction with the host immune
system. Their characterization and testing is also an emerging and very complex
area.
PMID- 28699789
TI - Real-world effectiveness of daily teriparatide in Japanese patients with
osteoporosis at high risk for fracture: final results from the 24-month Japan
Fracture Observational Study (JFOS).
AB - OBJECTIVE: The Japan Fracture Observational Study (JFOS), a prospective
observational study, investigated the real-world effectiveness of daily
teriparatide to reduce clinical fracture risk in osteoporotic patients. METHODS:
In routine clinical practice, Japanese patients initiated on teriparatide 20
MUg/day by subcutaneous injection were enrolled. The primary end-point was the
rate of clinical fractures at 6-month intervals over 24 months. Bone mineral
density (BMD), procollagen type 1 aminoterminal propeptide (P1NP), back pain, and
health-related quality-of-life (HRQoL) information was collected. RESULTS: Of
1,996 patients at baseline, 90.1% were female, and mean age was 76.9 years.
Teriparatide persistence at 12 and 24 months was 68.0% and 51.6%, respectively.
Compared to the first 6-month treatment interval, the odds ratio of fractures
decreased by 56.4% during 6-12 months, 51.6% during 12-18 months, and 58.8%
during 18-24 months (all p < .01). After 24 months, BMD increased by 17.2%
(lumbar spine) and 7.9% (total hip). After 6 months, P1NP levels increased by
259.3%. A reduction in back pain (100 mm visual analog scale) of 16.1 mm at 3
months was maintained through 24 months. HRQoL (pain, daily living activities,
general health) improved by >=10% at each post-baseline time point. Of 279
(14.6%) patients with >=1 adverse event (AE), 71 (3.7%) experienced >=1 drug
related AE (investigator assessed), including nausea (0.7%), dizziness (0.4%),
and decreased appetite (0.3%). Osteosarcoma was not reported; there were no new
safety signals. CONCLUSIONS: JFOS demonstrated effectiveness of teriparatide 20
MUg/day to reduce the risk of clinical fractures in Japanese patients in a real
world setting.
PMID- 28699790
TI - Safety of available and emerging drug therapies for hyperhidrosis.
AB - INTRODUCTION: Hyperhidrosis affects 4.8% of the U.S. population and has been
underestimated by physicians for long time despite considerable interference with
quality of life. Many patients suffer from primary (idiopathic) hyperhidrosis
which results from over-activity of sympathetic nerves and is restricted to
specific body areas, mostly the axillae, palms, soles, or head. Secondary
hyperhidrosis is caused by an underlying disease or the intake of medications and
often involves large parts of the body. Numerous effective therapies with topical
or systemic drugs and surgical options are available. Areas covered: Efficacy and
safety data on aluminum salts, anticholinergic drugs for topical or systemic
application, and on intradermal botulinum toxin injections used to treat
hyperhidrosis are critically evaluated, including data from clinical trials with
focus on possible side effects and long-term complications in dispute. Expert
opinion: Hyperhidrosis often responds well to available therapies. Depending on
the type of hyperhidrosis treatment should be topical/local or systemic. Most of
the side effects are mild, transient and easily manageable. In case of systemic
treatment with anticholinergics low dosing and up-titration of medication is
necessary to avoid severe adverse effects. Concerns about the promotion of breast
cancer and Alzheimer disease by topical aluminum salts are unsolved.
PMID- 28699791
TI - A synergistic protective effect of selenium and taurine against experimentally
induced myocardial infarction in rats.
AB - This study investigated the protective effect of subacute pre-adminsitration of
either selenium (Se), taurine (Tau), or both drugs in combination against
experimentally induced myocardial infarction (MI) in rats and illustrates the
possible mechanisms of action. While solely pre-administration of Se or Tau
resulted in partial amelioration in all of the measured parameters in MI rats,
concomitant administration of both drugs to MI rats significantly restored
contractility function by increasing LVSP and decreasing LVEDP and significantly
normalized serum levels of LDH, CK-MB and BNP and restored normal cardiac
architecture. This concomitant treatment acted by increasing the activity of
major antioxidant enzymes (SOD and GPx), decreasing the levels of inflammatory
markers including TNF-alpha, IL-6 as well as levels of Bcl-2 and caspase-3 and
downregulating mRNA levels of Bax and P53, markers of apoptosis. In conclusion, a
combination of Se and Tau provides a new strategy to alleviate MI-induced cardiac
dysfunction.
PMID- 28699792
TI - Novel approaches to the design of bioavailable melanotropins.
AB - INTRODUCTION: The melanocortin system is a primordial and critical system for
survival, involved in a wide variety of physiological functions. It includes
melanocortin receptors (MCRs) and melanotropin ligands (MCLs). MCRs are important
drug targets that can regulate several key physiological processes. Extensive
efforts have been made to develop peptide and peptidomimetics targeting
melanocortin receptors including MC1R, MC3R, MC4R and MC5R. Most research is
focused on developing potent and selective melanotropins. However, developing
bioavailable melanotropins remains challenging. Areas covered: Herein, the
authors summarize promising strategies for developing bioavailable MCLs by using
cyclized N-methylated melanotropins, and using cyclotide and tetrapeptide as
templates. They discuss their unique advantages in oral availability and
targeting MCRs in the central nervous system or in peripheral tissues. Finally,
they discuss the observed differences in thepharmacology of MCRs between in vitro
and in vivo tests. Expert opinion: N-methylated cyclized melanotropins have great
potential to become bio- available drugs targeting MCRs in the brain, while MCR
grafted cyclotides tend to target MCRs in peripheral tissue. A better
understanding of the biased signaling process is a new challenge and opportunity
for the future discovery of bioavailable MCLs.
PMID- 28699793
TI - Predictors of early treatment failure following initial therapy for systemic
immunoglobulin light-chain amyloidosis.
AB - We analysed factors predicting early treatment failure (ETF), after first-line
therapy for light-chain amyloidosis (AL). AL amyloidosis patients seen at Mayo
Clinic within 90 days of diagnosis, from 2006 to 2015, excluding those who died
within 3 months of initial therapy, were analysed retrospectively. ETF was
defined as progression requiring treatment change or death within 12 (ETF12) or
24 (ETF24) months of first-line treatment. Non-ETF included those with a follow
up of more than 12 or 24 months who had progression beyond 12 or 24 months. A
total of 724 patients met the study criteria; 244 (33.7%) had ETF12 and 388
(53.6%) had ETF24. Patients with ETF12 were older (64.1 vs. 62.2 years) with
higher prevalence of cardiac (81 vs. 64.1%) and multi-organ involvement (67.2 vs.
45.4%) and higher proportion of patients with t(11; 14) (58.5 vs. 44.3%) or in
higher Mayo 2012 stage (58.5 vs. 41.1%).The median follow-up was 5.4 years from
start of initial therapy. In multivariate analysis, presence of t(11; 14) and non
incorporation of autologous transplant in initial therapy are significant
predictors of ETF12 (p = .01and p = .003) and ETF24 (p = .0001 and p = .005)
while Mayo stage is predictive of ETF24 (p = .002), but not ETF12.
PMID- 28699794
TI - Valbenazine for the treatment of tardive dyskinesia.
AB - INTRODUCTION: Tardive dyskinesia (TD) is a hyperkinetic movement disorder that
may result from treatment with antipsychotics or other dopamine receptor blocking
agents. Underlying pathophysiology is incompletely understood but since the 1970s
dopamine depleting agents have been used to reduce involuntary movements. The
search for safe, effective treatments for TD is ongoing. Valbenazine, a novel
VMAT2 inhibitor, has recently been FDA approved for treatment of TD. Areas
covered: An overview of TD, unmet medical needs and current treatment guidelines
are presented. The background, chemistry and clinical development of valbenazine
to treat TD is detailed. A competitive market is developing as the treatment gap
is identified and potential therapies are discussed in context of a broader
market overview. Expert opinion: Antipsychotic use is growing among adults and
children in the U.S. Consequently, prevalence of TD is expected to rise.
Cessation of antipsychotics is often not possible as the psychiatric condition
may deteriorate. Increasing doses of an antipsychotic to suppress involuntary
movements is not sustainable long term as underlying TD worsens and movements
typically recur. There were no FDA approved treatments for TD. The approval of
valbenazine to treat TD is a critical step in addressing this gap in neurologic
care.
PMID- 28699795
TI - Provider perceptions of the assessment and rehabilitation of sexual functioning
after Traumatic Brain Injury.
AB - OBJECTIVE: To explore how health care professionals who work with individuals
with TBI address issues related to the assessment and treatment of sexuality
after TBI. METHODS: A survey composed of 53 questions was developed to evaluate
professional training, assessment of sexuality in individuals with TBI and
attitudes towards sexuality. The sample consisted of 324 self-identified TBI
health care professionals. RESULTS: Ninety seven per cent of participants
believed that sexuality should be discussed during rehabilitation; however, 36%
reported talking about it. Seventy nine per cent reported that their patients
have asked about sexuality after TBI, with 60% feeling calm and competent
addressing the topic. The main reason for not discussing the topic was that
patients do not ask for information (42%). Assessment (87%) and treatment of
sexuality (82%) in individuals with TBI are considered a part of their
professional responsibility. CONCLUSION: Despite recognition of the importance of
addressing the topic and the belief of it being their professional
responsibility, many professionals reported lack of training. Working to increase
comfort with the topic and providing comprehensive education on treating
sexuality may be beneficial.
PMID- 28699796
TI - Utilization and safety of proton-pump inhibitors and histamine-2 receptor
antagonists in children and adolescents: an observational cohort study.
AB - BACKGROUND: Little is known about the use of acid-suppressing treatments and
related safety events in children. OBJECTIVE: This study compared patient
characteristics and safety outcomes among children prescribed acid-suppressing
drugs for the first time. METHODS: The Health Improvement Network was used to
determine the characteristics of children prescribed a proton pump inhibitor
(PPI; esomeprazole or another PPI) or a histamine-2 receptor antagonist (H2RA) by
UK primary care physicians between October 2009 and September 2012. Pre-defined
safety outcomes were compared among the treatment groups in up to 18 months of
follow-up. RESULTS: The cohorts comprised 8,172 patients on PPIs (including 24
patients on esomeprazole) and 7,905 on H2RAs. The baseline characteristics were
similar between cohorts, although the children in the PPI cohorts tended to be
older. No safety outcomes occurred in the esomeprazole cohort. In the other-PPIs
cohort, 92 safety outcomes occurred, most commonly gastroenteritis (n = 36;
39.1%). In the H2RAs cohort, 193 safety outcomes occurred, most commonly
gastroenteritis (n = 62; 32.1%). The incidence of most safety outcomes was higher
in the H2RAs cohort than in the other-PPIs cohort, including failure to thrive
(3.11 [95% confidence interval (CI) = 2.25-4.28] vs 0.49 per 1,000 person-years
[95% CI = 0.22-1.07]) and gastroenteritis (5.27 [95% CI = 4.11-6.75] vs 3.04 per
1,000 person-years [95% CI = 2.20-4.20]). CONCLUSION: Esomeprazole is rarely
prescribed to children when they first require acid-suppressing medication,
compared with other PPIs/H2RAs. Overall, more safety outcomes occurred in the
H2RAs cohort than in the PPI cohorts.
PMID- 28699797
TI - Candidemia and invasive candidiasis among hospitalized neonates and pediatric
patients.
AB - OBJECTIVE: To investigate the epidemiology, treatment, length of stay (LOS) and
costs for neonatal and pediatric inpatients with invasive candidiasis (IC).
METHODS: The Cerner Health Facts Database was used to assess inpatients (2005
2014) identified by positive blood or cerebrospinal fluid (CSF) Candida cultures.
Log-transformed LOS and cost were examined in candidemia-only patients (n = 191)
using multivariable linear regression. RESULTS: A total of 202 patients had a
positive culture (blood: n = 192; CSF: n = 10; both: n = 2). The most prevalent
species were C. parapsilosis (n = 70, 34.7%), and C. albicans (n = 66, 32.7%).
Mean (SD) age was 5 (5.5) years; 30 (14.9%) patients were <4 months.
Comorbidities included sepsis (n = 85, 42.1%), coagulation disorders (n = 57,
28.2%), cancer (n = 64, 31.7%), and low birthweight (n = 26, 12.9%). Antifungals
(AFs) included azoles (57.4%), polyenes (28.7%), and echinocandins (35.1%); 20.8%
of patients received no AF during their encounter. The mean (SD) cost per
encounter was $97,392 ($149,253), with a mean (SD) LOS of 45.6 (59.5) days and
9.9% mortality at discharge. Results were similar across Candida species. In
regression analysis, intensive care unit (ICU) exposure, central catheter,
sepsis, AF >48 hours prior to index culture, and age <4 months were associated
with increased LOS; treatment at a non-teaching hospital was associated with
reduced LOS (p < .05). AF use >48 hours before index, in-hospital mortality,
Midwest region and ventricular shunt were associated with increased cost (p <=
.05). CONCLUSIONS: This analysis confirms the association between pediatric
candidemia and increased resource utilization and LOS. Given high observed rates
of potential under-treatment, an opportunity may exist to improve AF therapy in
this population.
PMID- 28699798
TI - Durability of response to dapagliflozin: a review of long-term efficacy and
safety.
AB - BACKGROUND: Due to the chronic nature of type 2 diabetes (T2D), it is essential
for an anti-diabetic drug to have durable efficacy and a good long-term safety
profile. Dapagliflozin is a member of a unique class of anti-diabetic drugs that
inhibit the sodium-glucose cotransporter 2 (SGLT-2) in the renal tubules and have
an insulin-independent mechanism of action. In short-term studies (<= 24 weeks),
dapagliflozin reduced glycated hemoglobin (A1c), weight, and systolic blood
pressure, and had a good safety profile. METHODS: This review summarizes the
findings of long-term studies that evaluated the efficacy and safety of
dapagliflozin. RESULTS: These findings indicate that dapagliflozin is effective
as monotherapy and in combination with other anti-hyperglycemic agents, including
insulin and oral anti-diabetic therapies, in improving glycemic control and
reducing blood pressure and weight for up to 4 years. The findings were fairly
consistent across various patient populations with T2D, including those with
cardiovascular disease (CVD) and mild renal impairment. Extended use of
dapagliflozin was not associated with an increase in safety signals over time.
Frequently observed adverse events (AEs) were consistent with the drug's
mechanism of action and were generally mild in intensity. No substantial impact
of dapagliflozin on renal function was observed, and findings show that the drug
is safe in T2D patients with CVD or mild renal impairment, as well as elderly
patients. CONCLUSIONS: The findings across the studies support the use of
dapagliflozin for the long-term treatment of T2D across a broad spectrum of
patients.
PMID- 28699799
TI - Immunization of BALB/c mice with pigeon IgY induces the production of anti-IgG
autoantibodies.
AB - The breakdown of immunological tolerance due to the activation of autoreactive B
and T cells triggers physiopathological processes. An example of such conditions
is the production of IgG autoantibodies specific for the Fc portion of IgG (anti
Fcgamma IgG). Previous reports have shown that patients with pigeon-related
hypersensitivity pneumonitis exhibit an increase in the serum levels of anti
Fcgamma IgG. There is no in vivo model for the study of this condition and the
immunological mechanisms of tolerance breakdown associated with sensitization by
pigeon antigens are still unknown. In this work, we show that the repeated
immunization of BALB/c mice with pigeon IgY during 16-weeks induces the
production of anti-Fcgamma IgG and keeps their high levels for seven weeks. The
late appearance of anti-Fcgamma IgG autoantibodies in the plasma is similar to
what has been reported in other experimental autoimmune models. With the
occurrence of anti-Fcgamma IgG, there is a reduction in the proportion of Foxp3 +
cells (regulatory T cells, Tregs) within the population of splenic CD4 + CD25 + T
cells. Thus, our data showed that the immunization of BALB/c mice with IgY
promotes the production of anti-Fcgamma IgG along with a decrease in Tregs in the
spleen. We propose that immunization of mice with pigeon antigens, like IgY can
provide a model to study the immunological mechanisms involved in the development
of pigeon-related hypersensitivity pneumonitis.
PMID- 28699800
TI - Towards the improvement in stability of an anti-Abeta single-chain variable
fragment, scFv-h3D6, as a way to enhance its therapeutic potential.
AB - ScFv-h3D6 is a single-chain variable fragment derived from the monoclonal
antibody bapineuzumab that prevents Abeta-induced cytotoxicity by capturing Abeta
oligomers. The benefits of scFv-h3D6 treatment in Alzheimer's disease are known
at the behavioural, cellular and molecular levels in the 3xTg-AD mouse model.
Antibody-based therapeutics are only stable in a limited temperature range, so
their benefit in vivo depends on their capability for maintaining the proper
fold. Here, we have stabilized the scFv-h3D6 folding by introducing the mutation
VH-K64R and combining it with the previously described elongation of the VL
domain (C3). The stabilities of the different scFv-h3D6 constructs were
calculated from urea and thermal denaturation followed by Trp-fluorescence, CD
and DSC and resulted in the order C3 > K64R/C3 > VH-K64R >= scFv-h3D6; showing
that the combination of both mutations was not additive, instead they partially
cancelled each other. The three mutants assayed showed a decreased aggregation
tendency but maintained their capability to aggregate in the form of worm-like
fibrils, basis of the protective effect of scFv-h3D6. Cytotoxicity assays showed
that all the mutants recovered cell viability of Abeta-treated neuroblastoma cell
cultures in a dose-dependent manner and with efficiencies that correlated with
stability, therefore improving the therapeutic ability of this antibody.
PMID- 28699801
TI - Statin use correlates with reduced risk of chronic osteomyelitis: a nationwide
case-control study in Taiwan.
AB - BACKGROUND/OBJECTIVE: Potential association between prior statin use and chronic
osteomyelitis is examined. METHODS: A nationwide case-control study was conducted
based on data taken from the Taiwan National Health Insurance program. The case
group includes 2338 subjects aged 20-84 years newly diagnosed for chronic
osteomyelitis from 2000 to 2013; the control group included 2338 randomly
selected subjects without chronic osteomyelitis matched for sex, age, and index
year. Statin use was respectively defined as "current", "recent" or "past" if the
most recent statin prescription was filled <3 months, 3-6 months or >=6 months
prior to the chronic osteomyelitis diagnosis. Relative risk of chronic
osteomyelitis associated with statin use was measured by the odds ratio (OR) with
95% confidence interval (CI) using the conditional logistic regression model.
RESULTS: After controlling for potential confounders, the adjusted ORs of chronic
osteomyelitis were 0.57 for subjects with current statin use (95% CI 0.45, 0.72),
0.80 for subjects with recent statin use (95% CI 0.48, 1.33), and 1.00 for
subjects with past statin use (95% CI 0.83, 1.20), compared patients with no
prior statin use. In further analysis, the adjusted ORs of chronic osteomyelitis
were 0.70 for subjects with cumulative statin use <12 months (95% CI 0.47, 1.07),
and 0.56 for subjects with cumulative statins use >=12 months (95% CI 0.41,
0.77), compared with those with no prior statin use. CONCLUSIONS: Current statin
use is associated with reduced concurrent diagnosis of chronic osteomyelitis,
particularly for a cumulative statin use >=12 months.
PMID- 28699802
TI - Positive correlation between blood pressure or heart rate and chymase-dependent
angiotensin II-forming activity in circulating mononuclear leukocytes measured by
new ELISA.
AB - The aim of the present study was to establish a convenient clinically applicable
assay method for chymase-dependent angiotensin II forming activity of circulating
mononuclear leukocytes (CML), which was potentially a marker of tissue chymase
activity. Using this method, association between CML chymase activity and
clinical parameters was determined. Cardiovascular outpatients (n = 170) without
taking antihypertensive medication were recruited. An ELISA for chymase-dependent
angiotensin II-forming activity in CML was established using Nma /Dnp-modified
angiotensin I. Logistic regression analysis revealed that age and male gender
were significant independent determinants of the increased CML chymase activity.
After adjustment by age and gender, the CML chymase activity was positively
correlated with systolic blood pressure, pulse rate, and the brain natriuretic
peptide level. The relation between blood pressure and CML chymase activity
suggests that it might reflect that increased tissue chymase activity contributes
to systemic high blood pressure and heart rate because plasma chymase is inactive
due to inhibitory plasma inhibitors.
PMID- 28699803
TI - Increased cancer risk in patients with periodontitis.
AB - BACKGROUND: Previous studies have noted a possible association between
periodontal diseases and the risk of various cancers. We assessed cancer risk in
a cohort of patients with moderate to severe periodontitis. METHODS: Patients
diagnosed with moderate to severe periodontitis by a periodontist between 2001
and 2010 were identified from the hospital registry. Patients younger than 35
years of age or with a prior cancer diagnosis were excluded. The age- and gender
standardized incidence rates (SIR) were calculated by dividing the number of
observed cases by the number of expected cases from Turkish National Cancer
Registry 2013 data. RESULTS: A total of 280 patients were included (median age
49.6, 54% female). Median follow-up was 12 years. Twenty-five new cancer cases
were observed. Patients with periodontitis had 77% increased risk of cancer (SIR
1.77, 95% CI 1.17-2.58, p = .004). Women with periodontitis had significantly
higher risk of breast cancer (SIR 2.40, 95% CI 0.88-5.33) and men with
periodontitis had significantly higher risk of prostate cancer (SIR 3.75, 95% CI
0.95-10.21) and hematological cancers (SIR 6.97, 95% CI 1.77-18.98). CONCLUSION:
Although showing a causal association necessitates further investigation, our
results support the idea that periodontitis might be associated with increased
cancer risk, particularly with hematological, breast and prostate cancers.
PMID- 28699804
TI - Real-world palbociclib dosing patterns and implications for drug costs in the
treatment of HR+/HER2- metastatic breast cancer.
AB - BACKGROUND: This study described real-world palbociclib dosing patterns and
associated impacts on treatment costs for HR+/HER2- metastatic breast cancer
(mBC) in the US. METHODS: Postmenopausal women with HR+/HER2- mBC who initiated
palbociclib-based therapy (initiation date = index date) between 02/03/2015
(palbociclib approval) and 02/29/2016, and continuous quarterly activity 1 year
before and 6 months after the index date, were identified in the Symphony Health
Solutions database. Rates of 1) dose reduction (>=25 mg dose decrease/daily), and
2) reduction or interruption (>60 day gap in continuous drug supply) were
assessed using Kaplan-Meier analyses. Drug wastage cost was estimated based on
overlapping days between two prescription fills: the last original dose fill and
the first reduced dose fill. RESULTS: 1,242 patients initiated palbociclib-based
therapy (mean age = 62.7 years, median follow-up = 8.7 months). During the 12
month post-index period, across the first four lines, dose reduction rates were
31.9-33.7% and dose reduction/interruption rates were 63.5-80.9%. A total of 411
(33.1%) patients changed dose, among whom 128 (31.1%) experienced prescription
fill overlap (average = 11.1 days). Mean potential drug wastage cost among
patients with fill overlap was $5,471. CONCLUSIONS: Most patients receiving
palbociclib experienced dose reduction or interruption early in treatment; the
associated drug wastage may lead to considerable costs.
PMID- 28699805
TI - Association of high sensitivity C-reactive protein and abdominal aortic aneurysm:
a meta-analysis and systematic review.
AB - OBJECTIVE: To evaluate the association of high sensitivity C-reactive protein
(hsCRP) with the presence of abdominal aortic aneurysm (AAA). METHODS: Medline,
Cochrane, Embase, and Google Scholar databases were searched until 22 June 2016
using the keywords predictive factors, biomarkers, abdominal aortic aneurysm,
prediction, high sensitivity C-reactive protein, and hsCRP. Prospective studies,
retrospective studies, and cohort studies were included. RESULTS: Twelve case
control studies were included in the meta-analysis with a total of 8345 patients
(1977 in the AAA group and 6368 in the control group). The pooled results showed
that AAA patients had higher hsCRP value than the control group (difference in
means = 1.827, 95% CI = 0.010 to 3.645, p = .049). Subgroup analysis found AAA
patients with medium or small aortic diameter (<50 mm) had higher hsCRP plasma
levels than the control group (difference in means = 1.301, 95% CI = 0.821 to
1.781, p < .001). In patients with large aortic diameter (>=50 mm), no difference
was observed in hsCRP levels between the AAA and control groups (difference in
means = 1.769, 95% CI = -1.387 to 4.925, p = .272). Multi-regression analysis
found the difference in means of hsCRP plasma levels between AAA and control
groups decreased as aortic diameter increased (slope = -0.04, p < .001),
suggesting that hsCRP levels may be inversely associated with increasing aneurysm
size. CONCLUSIONS: Our findings suggest that hsCRP levels may possibly be used as
a diagnostic biomarker for AAA patients with medium or small aortic diameter but
not for AAA patients with large aortic diameter. The correlation between serum
hsCRP level and AAA aneurysm is not conclusive due to the small number of
included articles and between-study heterogeneity.
PMID- 28699806
TI - Fibromyalgia as a cause of uncontrolled asthma: a case-control multicenter study.
AB - BACKGROUND: Fibromyalgia can affect the control of asthma when both diseases are
present in a single patient. OBJECTIVES: To characterize asthma in patients with
concomitant fibromyalgia to assess whether fibromyalgia is an independent factor
of asthma severity that influences poor asthma control. We also evaluated how
dyspnea is perceived by patients in order to demonstrate that alterations in the
perception of airway obstruction may be responsible for poor asthma control.
METHODS: This was a cross-sectional case-control multicenter study, in which 56
patients in the asthma and fibromyalgia group were matched to 36 asthmatics by
sex, approximate age, and asthma severity level. All patients were women. Study
variables included the Asthma Control Test (ACT), the Mini Asthma Quality of Life
Questionnaire (MiniAQLQ), the Nijmegen hyperventilation syndrome questionnaire,
the Hospital Anxiety and Depression Scale, and perception of dyspnea after acute
bronchoconstriction. RESULTS: Although patients in both study groups showed
similar asthma severity and use of anti-asthmatic drugs, patients in the asthma
and fibromyalgia group showed lower scores on the ACT and MiniAQLQ
questionnaires, and higher scores of anxiety and depression as well as
hyperventilation compared to asthma patients without fibromyalgia. All these
differences were statistically significant. CONCLUSIONS: Fibromyalgia in patients
with asthma influences poor control of the respiratory disease and is associated
with altered perception of dyspnea, hyperventilation syndrome, high prevalence of
depression and anxiety, and impaired quality of life. CLINICAL IMPLICATIONS:
Fibromyalgia may be considered a risk factor for uncontrolled asthma in patients
suffering from asthma and fibromyalgia concomitantly.
PMID- 28699807
TI - Personalizing antiplatelet prescribing using genetics for patients undergoing
percutaneous coronary intervention.
AB - INTRODUCTION: Clopidogrel is commonly prescribed with aspirin to reduce the risk
for adverse cardiovascular events after percutaneous coronary intervention (PCI).
However, there is significant inter-patient variability in clopidogrel response.
The CYP2C19 enzyme is involved in the biotransformation of clopidogrel to its
pharmacologically active form, and variation in the CYP2C19 gene contributes to
clopidogrel response variability. Areas covered. This article describes the
impact of CYP2C19 genotype on clopidogrel pharmacokinetics, pharmacodynamics, and
effectiveness. Examples of clinical implementation of CYP2C19 genotype-guided
antiplatelet therapy for patients undergoing PCI are also described as are
emerging outcomes data with this treatment approach. Expert commentary. A large
clinical trial evaluating outcomes with CYP2C19 genotype-guided antiplatelet
therapy after PCI is on-going. In the meantime, data from pragmatic and
observational studies and smaller trials support improved outcomes with
genotyping after PCI and use of alternative antiplatelet therapy in patients with
a CYP2C19 genotype associated with reduced clopidogrel effectiveness.
PMID- 28699808
TI - The Effects of Physical Exercise and Cognitive Training on Memory and
Neurotrophic Factors.
AB - This study examined the combined effect of physical exercise and cognitive
training on memory and neurotrophic factors in healthy, young adults. Ninety-five
participants completed 6 weeks of exercise training, combined exercise and
cognitive training, or no training (control). Both the exercise and combined
training groups improved performance on a high-interference memory task, whereas
the control group did not. In contrast, neither training group improved on
general recognition performance, suggesting that exercise training selectively
increases high-interference memory that may be linked to hippocampal function.
Individuals who experienced greater fitness improvements from the exercise
training (i.e., high responders to exercise) also had greater increases in the
serum neurotrophic factors brain-derived neurotrophic factor and insulin-like
growth factor-1. These high responders to exercise also had better high
interference memory performance as a result of the combined exercise and
cognitive training compared with exercise alone, suggesting that potential
synergistic effects might depend on the availability of neurotrophic factors.
These findings are especially important, as memory benefits accrued from a
relatively short intervention in high-functioning young adults.
PMID- 28699809
TI - Acute Stress Time-dependently Modulates Multiple Memory Systems.
AB - Acute stress has been shown to modulate the engagement of different memory
systems, leading to preferential expression of stimulus-response (SR) rather than
episodic context memory when both types of memory can be used. However, questions
remain regarding the cognitive mechanism that underlies this bias in humans
specifically, how each form of memory is individually influenced by stress in
order for SR memory to be dominant. Here we separately measured context and SR
memory and investigated how each was influenced by acute stress after learning
(Experiment 1) and before retrieval (Experiment 2). We found that postlearning
stress, in tandem with increased adrenergic activity during learning, impaired
consolidation of context memory and led to preferential expression of SR rather
than context memory. Preretrieval stress also impaired context memory, albeit
transiently. Neither postlearning nor preretrieval stress changed the expression
of SR memory. However, individual differences in cortisol reactivity immediately
after learning were associated with variability in initial SR learning. These
results reveal novel cognitive mechanisms by which stress can modulate multiple
memory systems.
PMID- 28699810
TI - A balanced level of profilin-1 promotes stemness and tumor-initiating potential
of breast cancer cells.
AB - Profilin-1 (Pfn1) is an important actin-regulatory protein that is downregulated
in human breast cancer and when forcibly elevated, it suppresses the tumor
initiating ability of triple-negative breast cancer cells. In this study, we
demonstrate that Pfn1 overexpression reduces the stem-like phenotype (a key
biologic feature associated with higher tumor-initiating potential) of MDA-MB-231
(MDA-231) triple-negative breast cancer cells. Interestingly, the stem-like trait
of MDA-231 cells is also attenuated upon depletion of Pfn1. A comparison of
cancer stem cell gene (CSC) gene expression signatures between depleted and
elevated conditions of Pfn1 further suggest that Pfn1 may be somehow involved in
regulating the expression of a few CSC-related genes including MUC1, STAT3, FZD7,
and ITGB1. Consistent with the reduced stem-like phenotype associated with loss
of-function of Pfn1, xenograft studies showed lower tumor-initiating frequency of
Pfn1-depleted MDA-231 cells compared to their control counterparts. In MMTV:PyMT
mouse model, homozygous but not heterozygous deletion of Pfn1 gene leads to
severe genetic mosaicism and positive selection of Pfn1-proficient tumor cells
further supporting the contention that a complete lack of Pfn1 is likely not
conducive for efficient tumor initiation capability of breast cancer cells. In
summary, these findings suggest that the maintenance of optimal stemness and
tumor-initiating ability of breast cancer cells requires a balanced expression of
Pfn1.
PMID- 28699811
TI - Fatigue, alopecia and stomatitis among patients with breast cancer receiving
cyclin-dependent kinase 4 and 6 inhibitors: a systematic review and meta
analysis.
AB - BACKGROUND: Cyclin-dependent kinase (CDK) inhibitors emerge as efficacious agents
in hormone positive metastatic breast cancer with more acceptable toxicity
profiles than cytotoxic chemotherapy. However, some adverse effects such as
fatigue, alopecia and stomatitis, vastly concern patients. METHODS: The search
was conducted in PubMed, American Society of Clinical Oncology meeting library,
European Society for Medical Oncology meeting abstract, and the San Antonio
meeting abstract databases. We identified phase 2 or 3 trials recruiting patients
with breast cancer, randomized to receive hormonal treatment plus either CDK4/6
inhibitors or placebo. We considered studies providing incidence of fatigue,
alopecia and stomatitis relevant. RESULTS: One thousand records were screened. 34
studies were considered relevant. Four studies were found to be eligible for meta
analysis with a total of 2007 patients. The relative risk for all grade fatigue
was 1.34 [95% CI: 1.17-1.54, p < 0.0001], for all grade alopecia was 2.14 [95%
CI: 1.23-3.73, p = 0.007], and for all grade stomatitis 4.87 [95% CI: 2.11-11.24,
p = 0.0002]. In addition, the relative risk for high grade fatigue was 2.40 [95%
CI: 1.10-5.26, p = 0.03]. CONCLUSION: CDK4/6 inhibitors were associated with an
increased risk of fatigue, alopecia and stomatitis. Further studies with self
reported questionnaires may elucidate the impact of the increased risk of these
selected adverse effects on the patients' quality of life.
PMID- 28699812
TI - Epitope mapping of Ebola virus dominant and subdominant glycoprotein epitopes
facilitates construction of an epitope-based DNA vaccine able to focus the
antibody response in mice.
AB - We performed epitope mapping studies on the major surface glycoprotein (GP) of
Ebola virus (EBOV) using Chemically Linked Peptides on Scaffolds (CLIPS), which
form linear and potential conformational epitopes. This method identified
monoclonal antibody epitopes and predicted additional epitopes recognized by
antibodies in polyclonal sera from animals experimentally vaccinated against or
infected with EBOV. Using the information obtained along with structural modeling
to predict epitope accessibility, we then constructed 2 DNA vaccines encoding
immunodominant and subdominant epitopes predicted to be accessible on EBOV GP.
Although a construct designed to produce a membrane-bound oligopeptide was poorly
immunogenic, a construct generating a secreted oligopeptide elicited strong
antibody responses in mice. When this construct was administered as a boost to a
DNA vaccine expressing the complete EBOV GP gene, the resultant antibody response
was focused largely toward the less immunodominant epitopes in the oligopeptide.
Taken together, the results of this work suggest a utility for this method for
immune focusing of antibody responses elicited by vaccination.
PMID- 28699813
TI - Prolylcarboxypeptidase (PrCP) inhibitors and the therapeutic uses thereof: a
patent review.
AB - INTRODUCTION: Prolylcarboxypeptidase (PrCP) is a serine protease that produces or
degrades signaling proteins in several important pathways including the renin
angiotensin system (RAS), kallikrein-kinin system (KKS) and pro-opiomelanocortin
(POMC) system. PrCP has the potential to be a therapeutic target for
cardiovascular, inflammatory and metabolic diseases. Numerous classes of PrCP
inhibitors have been developed by rational drug design and from high-throughput
screening hits. These inhibitors have been tested in mouse models to assess their
potential as new therapeutics. Areas Covered: This review covers the relevant
studies that support PrCP as a target for drug discovery. All the significant
patent applications and primary literature concerning the development of PrCP
inhibitors are discussed. Expert Opinion: The pathways where PrCP is known to
operate are complex and many aspects remain to be characterized. Many potent
inhibitors of PrCP have been tested in vivo. The variable results obtained from
in vivo studies with PrCP inhibitors suggest that additional understanding of the
biochemistry and the required therapeutic inhibitor levels is necessary.
Additional fundamental research into the signaling pathways is likely required
before the true therapeutic potential of PrCP inhibition will be realized.
PMID- 28699814
TI - Survival times for cats with hyperthyroidism treated with a 3.35 mCi iodine-131
dose: a retrospective study of 96 cases.
AB - Objectives Radioiodine (131I) dose determination using radiotracer kinetic
studies or scoring systems, and fixed relatively high 131I dose (ie, 4 or 5 mCi)
administration, are effective and associated with prolonged survival times for
hyperthyroid cats. The latter method is less complicated but could expose
patients and veterinary personnel to unnecessary levels of radiation. The aim of
this study was to retrospectively evaluate the efficacy of a fixed 3.35 mCi 131I
dose for the treatment of 96 hyperthyroid cats with no length estimation for any
palpated goitre ?20 mm, assess outcome and identify factors associated with
survival. Methods Serum total thyroxine concentrations at diagnosis and at follow
up times, survival times and cause of death were recorded. Multivariable Cox
regression analysis was used to identify factors associated with time to any
cause of death from 131I therapy initiation. Results Administration of a median
(interquartile range) dose of 3.35 mCi (3.27-3.44 mCi) radioiodine was an
effective treatment in 94/96 cats, but two cats remained hyperthyroid. No death
related to hyperthyroidism was recorded. Median survival time was 3.0 years; the
1 and 2 year survival rates after 131I therapy were 90% and 78%, respectively.
Low body weight (?3.1 kg; adjusted hazard ratio [aHR] 5.88; 95% confidence
interval [CI] 2.22-16.67; P <0.01) and male gender (aHR 2.63; 95% CI 1.01-7.14; P
= 0.04) were independently associated with death, whereas age, prior treatment
with antithyroid drugs, reason for treatment and pretreatment azotaemia were not.
Conclusions and relevance This study suggests that a fixed 3.35 mCi 131I dose
treatment is effective for hyperthyroid cats with goitre(s) with a maximal length
estimation <20 mm, that long-term survival can be achieved and that low body
weight and male gender are significantly associated with shorter survival times.
PMID- 28699815
TI - Improving recruitment to healthcare research studies: clinician judgements
explored for opting mental health service users out of the time to change
viewpoint survey.
AB - BACKGROUND: There are significant challenges across the research pathway,
including participant recruitment. This paper aims to explore the impact of
clinician recruitment decision-making on sampling for a national mental health
survey. METHOD: Clinical teams in 20 English mental healthcare provider
organisations screened caseload lists, opting-out people whom, in their
judgement, should not be approached to participate in a survey about stigma and
discrimination. The reasons for each individual opted-out were requested. We
assess these reasons against study recruitment criteria and investigated the
impact of variations in opt-out rates on response rates and study findings.
RESULTS: Over 4 years (2009-2012), 37% (28,592 people) of the total eligible
sampling frame were excluded. Exclusions comprised three categories: clinical
teams did not screen their lists within recruitment period (12,392 people: 44%);
protocol-specified exclusions (8364 people: 29%); clinician opt-outs queried by
research team (other reasons were given) (7836, 28%). Response rates were
influenced by decision-making variations. CONCLUSIONS: Large numbers of people
were denied the opportunity to choose for themselves whether to participate or
not in the Viewpoint Survey. The clinical research community, and their employing
organisations, require support to better understand the value of research and
best practice for research recruitment.
PMID- 28699817
TI - How may PI(3,5)P2 impact on vacuolar acidification?
PMID- 28699816
TI - Enrichment of Ly6Chi monocytes by multiple GM-CSF injections with HBV vaccine
contributes to viral clearance in a HBV mouse model.
AB - Adjuvants are considered a necessary component for HBV therapeutic vaccines but
few are licensed in clinical practice due to concerns about safety or efficiency.
In our recent study, we established that a combination protocol of 3-day
pretreatments with GM-CSF before a vaccination (3 * GM-CSF+VACCINE) into the same
injection site could break immune tolerance and cause over 90% reduction of HBsAg
level in the HBsAg transgenic mouse model. Herein, we further investigated the
therapeutic potential of the combination in AAV8-1.3HBV-infected mice. After 4
vaccinations, both serum HBeAg and HBsAg were cleared and there was a 95%
reduction of HBV-positive hepatocytes, in addition to the presence of large
number of infiltrating CD8+ T cells in the livers. Mechanistically, the HBV
specific T-cell responses were elicited via a 3 * GM-CSF+VACCINE-induced
conversion of CCR2-dependent CD11b+ Ly6Chi monocytes into CD11b+CD11c+ DCs.
Experimental depletion of Ly6Chi monocytes resulted in a defective HBV-specific
immune response thereby abrogating HBV eradication. This vaccination strategy
could lead to development of an effective therapeutic protocol against chronic
HBV in infected patients.
PMID- 28699818
TI - Implementing brief Dynamic Interpersonal Therapy (DIT) in a VA Medical Center.
AB - BACKGROUND: Given increasing mental health needs in the VA, identifying
strategies to deliver new services is critical. AIMS: This paper describes the
process of navigating provider, patient and systems barriers of an initiative to
increase choice, access and quality of psychotherapy at the VA by incorporating
an evidence-based short-term, psychodynamic psychotherapy. METHODS: Brief Dynamic
Interpersonal Therapy (DIT) was selected as a viable model for implementation.
Data were gathered on the process of implementation, barriers, Veterans seen, and
access to psychodynamic psychotherapy. RESULTS: Nine psychologists and 22 masters
level pre-doctoral psychology externs have delivered DIT to 73 Veterans. Veterans
referred for psychodynamic psychotherapy annually increased 360%. Furthermore,
DIT has become the dominant form of psychodynamic psychotherapy requested of the
psychology service representing 70.1% of psychodynamic psychotherapy referrals.
Strategies are presented for addressing: (1) provider ability, flexibility and
motivation, (2) Veteran perception of relevance, distinctiveness and adaptability
to complex presenting issues and (3) administrative support. CONCLUSIONS:
Implementing an evidence-based short-term psychodynamic treatment option in the
VA is feasible. VA mental health providers can be trained in brief psychodynamic
psychotherapy and can successfully implement those approaches in VA settings.
Finally, psychodynamic treatment approaches may serve as a promising alternative
to currently available treatments.
PMID- 28699819
TI - Targeting cytokines in asthma therapy: could IL-37 be a solution?
PMID- 28699821
TI - Physical activity in patients with COPD: the impact of comorbidities.
AB - INTRODUCTION: Comorbidities are common in patients with chronic obstructive
pulmonary disease (COPD) and it plays an important role on physical activity (PA)
in this population. Since low PA levels have been described as a key factor to
predict morbi-mortality in COPD, it seems crucial to review the current
literature available on this topic. Areas covered: This review covers the most
common comorbidities found in COPD, their prevalence and prognostic implications.
We explore the differences in PA between COPD patients with and without
comorbidities, as well as the impact of the number or type of comorbidities on
activity levels of this population. The effect of different comorbidities on
activities of daily living in patients with COPD is also reviewed. Finally, we
discuss options for the treatment of inactivity in COPD patients considering
their comorbidities and limitations. Expert commentary: Comorbidities are highly
prevalent in patients with COPD and further deteriorate PA levels in this
population. Despite the wide range of interventions available in COPD, the
evidence in the field seems to point at PA coaching with feedback on individual
goals and longer lasting PR programmes with more than 12 weeks of duration when
attempting to raise the activity levels of this population.
PMID- 28699820
TI - Expanded strain coverage for a highly successful public health tool: Prophylactic
9-valent human papillomavirus vaccine.
AB - Human papillomavirus is considered the causative factor for cervical cancer,
which accounts for approximately 5% of the global cancer burden and more than
600,000 new cases annually that are attributable to HPV infection worldwide. The
first-generation prophylactic HPV vaccines, Gardasil(r) and Cervarix(r), were
licensed approximately a decade ago. Both vaccines contain the most prevalent
high-risk types, HPV16 and 18, which are associated with 70% of cervical cancer.
To further increase the type coverage, 5 additional oncogenic HPV types (31, 33,
45, 52 and 58) were added to the existing Gardasil-4 to develop a 9-valent HPV
vaccine (9vHPV), Gardasil 9(r), increasing the potential level of protection from
~70% to ~90%. The efficacy of the vaccine lies primarily in its ability to elicit
type-specific and neutralizing antibodies to fend off the viral infection.
Therefore, type-specific and neutralizing murine monoclonal antibodies (mAbs)
were used to quantitate the antigenicity of the individual vaccine antigens and
to measure the antibody levels in the serum samples from vaccinees in a type- and
epitope-specific manner in a competitive immunoassay. Assays for 9vHPV are
extended from the proven platform used for 4vHPV by developing and adding new
mAbs against the additional types. In Phase III clinical trials, comparable
safety profile and immunogenicity against the original 4 types were demonstrated
for the 9vHPV vaccine, and these were comparable to the 4vHPV vaccine. The
efficacy of the 9vHPV vaccine was established in trials with young women.
Immunobridging for younger boys and girls was performed, and the results showed
higher immunogenicity in the younger age group. In a subsequent clinical trial,
the 2-dose regimen of the 9vHPV vaccine used among girls and boys aged 9-14 y
showed non-inferior immunogenicity to the regular 3-dose regimen for young women
(aged 16-26 years). Overall, the clinical data and cost-effectiveness analysis
for the 9vHPV vaccine support its widespread use to maximize the impact of this
important, life-saving vaccine.
PMID- 28699822
TI - A bioencapsulation and drying method increases shelf life and efficacy of
Metarhizium brunneum conidia.
AB - This study reports the development of encapsulated and dried entomopathogenic
fungus Metarhiuzm brunneum with reduced conidia content, increased conidiation, a
high drying survival and enhanced shelf life. Dried beads prepared with the
fillers corn starch, potato starch, carboxymethylcellulose or autoclaved baker's
yeast, showed enhanced survival with increasing filler content. The maximum
survival of 82% was found for beads with 20% corn starch at <0.1 water activity.
While increasing starch content inhibits the conidiation, autoclaved baker's
yeast and a combination with starch enhanced the conidiation to 1.0 * 108
conidia/bead. Beads with conidia content reduced to 0.01% multiplied conidia in a
"microfermentation" by the factor 1000. A bioassay confirmed that conidia formed
from rehydrated beads were virulent against Tenebrior molitor larvae. After six
months of storage, encapsulated conidia showed improved shelf life compared to
non-formulated conidia. This "microfermenter" will pave the way for encapsulated
fungi to be used as cost-effective biocontrol agents.
PMID- 28699823
TI - The GMZ2 malaria vaccine: from concept to efficacy in humans.
AB - INTRODUCTION: GMZ2 is a recombinant protein consisting of conserved domains of
GLURP and MSP3, two asexual blood-stage antigens of Plasmodium falciparum, and is
designed with the aim of mimicking naturally acquired anti-malarial immunity. The
rationale for combining these two antigens is based on a series of immune
epidemiological studies from geographically diverse malaria endemic regions;
functional in vitro studies; and pre-clinical studies in rodents and New World
monkeys. GMZ2 adjuvanted with alhydrogel(r) (alum) was well tolerated and
immunogenic in three phase 1 studies. The recently concluded phase 2 trial of
GMZ2/alum, involving 1849 participants 12 to 60 month of age in four countries in
West, Central and Eastern Africa, showed that GMZ2 is well tolerated and has
some, albeit modest, efficacy in the target population. Areas covered: PubMed (
www.ncbi.nlm.nih.gov/pubmed ) was searched to review the progress and future
prospects for clinical development of GMZ2 sub-unit vaccine. We will focus on
discovery, naturally acquired immunity, functional activity of specific
antibodies, sequence diversity, production, pre-clinical and clinical studies.
Expert commentary: GMZ2 is well tolerated and has some, albeit modest, efficacy
in the target population. More immunogenic formulations should be developed.
PMID- 28699824
TI - Barium-cross-linked alginate-gelatine microcapsule as a potential platform for
stem cell production and modular tissue formation.
AB - Influence of gelatine concentration and cross-linker ions of Ca2+ and Ba2+ was
evaluated on characteristics of alginate hydrogels and proliferation behaviours
of model adherent and suspendable stem cells of fibroblast and U937 embedded in
alginate microcapsules. Increasing gelatine concentration to 2.5% increased
extent of swelling to 15% and 25% for barium- and calcium-cross-linked hydrogels,
respectively. Mechanical properties also decreased with increasing swelling of
hydrogels. Both by increasing gelatine concentration and using barium ions
increased considerably the proliferation of encapsulated model stem cells. Barium
cross-linked alginate-gelatine microcapsule tested for bone building block showed
a 13.5 +/- 1.5-fold expansion for osteoblast cells after 21 days with deposition
of bone matrix. The haematopoietic stem cells cultured in the microcapsule after
7 days also showed up to 2-fold increase without adding any growth factor. The
study demonstrates that barium-cross-linked alginate-gelatine microcapsule has
potential for use as a simple and efficient 3D platform for stem cell production
and modular tissue formation.
PMID- 28699825
TI - Engaging end-users in intervention research study design.
AB - OBJECTIVE: Coordinated Healthcare Interventions for Childhood Asthma Gaps in
Outcomes (CHICAGO) Plan is a 3-arm multicenter pragmatic trial to evaluate asthma
interventions in high-risk Chicago children presenting to emergency departments
(ED) with asthma. A formative evaluation with end-users to provide input into the
trial design and outcome instruments was conducted prior to trial initiation.
METHODS: A multi-level data gathering framework from the field of design and
standard qualitative methods was employed. This included one focus group with
asthma Community Health Workers (N = 8), two focus groups with caregivers of
children with asthma (N = 9), in-home interviews with caregivers (N = 9), key
informant interviews at six EDs and outpatient clinical sites (N = 19), and ED
tours and observations (N = 6). Data were presented, discussed, and organized
into themes. RESULTS: Data indicated that changes to the study design and
discharge tool were warranted. A key insight was that ED discharge protocols
typically place patient education at a single inopportune time, as families are
preparing to leave the ED. At this point in time, families are less receptive to
education due to fatigue and a desire to expedite the discharge process. The
trial design was modified to reposition the discharge asthma plan to occur at
earlier "teachable moments." Delivery of the asthma discharge plan was assigned
to study-employed ED coordinators instead of ED providers and staff. Other
potential challenges to study recruitment and implementation were raised and
addressed. CONCLUSIONS: Engagement of end-users in the design phase of
implementation research is critical to improve research feasibility and
relevance.
PMID- 28699826
TI - Contralateral Associated Movements Correlate with Poorer Inhibitory Control,
Attention and Visual Perception in Preschool Children.
AB - Contralateral associated movements (CAMs) frequently occur in complex motor
tasks. We investigated whether and to what extent CAMs are associated with
inhibitory control among preschool children in the Swiss Preschoolers' Health
Study. Participants were 476 healthy, typically developing children (mean age =
3.88 years; 251 boys) evaluated on two consecutive afternoons. The children
performed the Zurich Neuromotor Assessment, the statue subtest of the
Neuropsychological Assessment for Children (NEPSY), and cognitive tests of the
Intelligence and Development Scales-Preschool (IDS-P). CAMs were associated with
poor inhibitory control on the statue test and poor selective attention and
visual perception on the IDS-P. We attributed these findings to preschoolers'
general immaturity of the central nervous system.
PMID- 28699827
TI - Evaluation of a passive method for determining particle penetration through
protective clothing materials.
AB - The risk of workers' exposure to aerosolized particles has increased with the
upsurge in the production of engineered nanomaterials. Currently, a whole-body
standard test method for measuring particle penetration through protective
clothing ensembles is not available. Those available for respirators neglect the
most common challenges to ensembles, because they use active vacuum-based
filtration, designed to simulate breathing, rather than the positive forces of
wind experienced by workers. Thus, a passive method that measures wind-driven
particle penetration through ensemble fabric has been developed and evaluated.
The apparatus includes a multidomain magnetic passive aerosol sampler housed in a
shrouded penetration cell. Performance evaluation was conducted in a
recirculation aerosol wind tunnel using paramagnetic Fe3O4 (i.e., iron (II, III)
oxide) particles for the challenge aerosol. The particles were collected on a PVC
substrate and quantified using a computer-controlled scanning electron
microscope. Particle penetration levels were determined by taking the ratio of
the particle number collected on the substrate with a fabric (sample) to that
without a fabric (control). Results for each fabric obtained by this passive
method were compared to previous results from an automated vacuum-based active
fractional efficiency tester (TSI 3160), which used sodium chloride particles as
the challenge aerosol. Four nonwoven fabrics with a range of thicknesses,
porosities, and air permeabilities were evaluated. Smoke tests and flow modeling
showed the passive sampler shroud provided smooth (non-turbulent) air flow along
the exterior of the sampler, such that disturbance of flow stream lines and
distortion of the particle size distribution were reduced. Differences between
the active and passive approaches were as high as 5.5-fold for the fabric with
the lowest air permeability (0.00067 m/sec-Pa), suggesting the active method
overestimated penetration in dense fabrics because the active method draws air at
a constant flow rate regardless of the resistance of the test fabric. The passive
method indicated greater sensitivity since penetration decreased in response to
the increase in permeability.
PMID- 28699828
TI - Glioma targeted delivery strategy of doxorubicin-loaded liposomes by dual-ligand
modification.
AB - The blood-brain barrier (BBB) is the protective parclose of brain safety, but it
is also the main obstacle of the drug delivery to cerebral parenchyma, which
hamper therapy for brain diseases. In this work, a glioma targeted drug delivery
system was developed through loading doxorubicin into Angiopep-2 and TAT peptide
dual-modified liposomes (DOX-TAT-Ang-LIP). Low-density lipoprotein receptor
related protein-1 (LRP1) was one receptor overexpressed on both BBB and glioma
cytomembranes. Angiopep-2, a specific ligand of LRP1, exhibited high LRP1 binding
efficiency. Additionally, TAT could penetrate through cell membranes without
selectivity via an unsaturated pathway. To avoid the receptor saturation of
Angiopep-2, TAT was also conjugated on the surface of liposomes, providing that
the liposomes not only have effective BBB penetrating effect, but also have the
glioma targeting function. The prepared DOX liposomes appeared good stability and
narrow dispersity in serum with a diameter of 90 nm, and exhibited sustained DOX
release behaviors. The conjunctions of Angiopep-2 and TAT were confirmed by 1H
NMR spectra. The BBB model, cellular uptake observations, antiproliferation
study, and the cell ultrastructure analyses suggested that DOX-TAT-Ang-LIP could
not only penetrate through BBB via transcytosis, but also concentrate in glioma,
then enter into glioma cells and finally result in the necrosis of glioma cells.
PMID- 28699829
TI - Association between Nonmedical Marijuana and Pain Reliever Uses among Individuals
Aged 50.
AB - Marijuana and pain reliever use for medical and nonmedical purposes has been
increasing among older adults. Using the 2012-2013 U.S. National Survey on
Alcohol and Related Conditions (NESARC-III), this study examined: (1) the
association between past-year nonmedical marijuana and pain reliever use among
adults aged 50+ years (N = 14,715); and (2) sociodemographic, health, and pain
related correlates of nonmedical marijuana and/or pain reliever use. The findings
show that 3.87% and 3.12%, respectively, used marijuana and pain relievers
nonmedically and 14.40% of marijuana users, compared to 2.67% of nonusers, used
pain relievers nonmedically. Controlling for sociodemographics, health status,
pain interference, and mental and other substance use disorders, marijuana use
anduse disorder were significantly associated with nonmedical pain reliever use
and opioid use disorder, respectively. Compared to marijuana users (with or
without nonmedical use of pain relievers), nonmedical pain reliever users
(without marijuana) are older, married, and women. Users of both substances
nonmedically are a small group (0.56% of the 50+ age group), but they are at
greatest risk of lifetime opioid, alcohol, and nicotine use disorders. Pain
interference is a significant correlate of nonmedical pain reliever use.
Healthcare providers should assess for the nonmedical use of these
medicines/drugs and help older adults receive effective pain treatment.
PMID- 28699830
TI - cag Pathogenicity island-dependent upregulation of matrix metalloproteinase-7 in
infected patients with Helicobacter pylori.
AB - Helicobacter pylori (H. pylori) infection has been involved in the pathogenesis
of most important gastroduodenal diseases. Matrix metalloproteinases (MMPs) are a
large family of zincendopeptidases which play important roles in degradation of
extracellular matrix (ECM) and various inflammatory diseases. Therefore, we
examined MMP-7 mRNA levels in the gastric mucosa of patients with H. pylori
infection and evaluated the effects of virulence factors, such as vacA
(vacuolating cytotoxin A) and cagA (cytotoxin-associated gene), in H. pylori
infected patients upon the MMP-7 mRNA mucosal levels. We also determined the
correlation between mucosal MMP-7 mRNA levels and the types of disease. Total RNA
was extracted from gastric biopsies of 50 H. pylori-infected patients and 50
uninfected individuals. Mucosal MMP-7 mRNA expression level in H. pylori-infected
and non-infected gastric biopsies was determined by real-time polymerase chain
reaction (PCR). The presences of cagA and vacA virulence factors was evaluated
using PCR. MMP-7 expression was significantly higher in biopsies of patients
infected with H .pylori compared to uninfected individuals. In addition, mucosal
MMP-7 mRNA expression in H. pylori-infected patients significantly associated
with the cagA status and the types of disease. Our results suggest that MMP-7
might be involved in the pathogenesis of H. pylori. Peptic ulcer was associated
with cag pathogenicity island-dependent MMP-7 upregulation.
PMID- 28699831
TI - Motivated malleability: Frontal cortical asymmetry predicts the susceptibility to
social influence.
AB - Humans, just as many other animals, regulate their behavior in terms of
approaching stimuli associated with pleasure and avoiding stimuli linked to harm.
A person's current and chronic motivational direction - that is, approach versus
avoidance orientation - is reliably reflected in the asymmetry of frontal
cortical low-frequency oscillations. Using resting electroencephalography (EEG),
we show that frontal asymmetry is predictive of the tendency to yield to social
influence: Stronger right- than left-side frontolateral activation during a
resting-state session prior to the experiment was robustly associated with a
stronger inclination to adopt a peer group's judgments during perceptual decision
making (Study 1). We posit that this reflects the role of a person's chronic
avoidance orientation in socially adjusted behavior. This claim was strongly
supported by additional survey investigations (Studies 2a, 2b, 2c), all of which
consistently revealed that trait avoidance was positively linked to the
susceptibility to social influence. The present contribution thus stresses the
relevance of chronic avoidance orientation in social conformity, refining (yet
not contradicting) the longstanding view that socially influenced behavior is
motivated by approach-related goals. Moreover, our findings valuably underscore
and extend our knowledge on the association between frontal cortical asymmetry
and a variety of psychological variables.
PMID- 28699832
TI - Neuropsychological Effects of Placebo Stimulants in College Students.
AB - Many college students underestimate or ignore the side-effects associated with
nonmedical use of prescription stimulants (NMUPS) and are motivated by hopes of
academic enhancement. The present study measured the effect a placebo stimulant
and personal expectancies have on subjective physiological changes and cognitive
enhancement. Undergraduate college students participated in a two-phase study.
Phase 1 (n = 305) involved completing an online survey to gather distal study
variables and individual stimulant expectancy data. Phase 2 (n = 166) required
students to attend an in-person session where they completed physiological and
neuropsychological measures (e.g., Physical Symptom Checklist, Digit Span,
Passage Comprehension). Students were randomized to receive a placebo stimulant
medication (experimental) or no medication (control). Following a 30-minute
absorption period, participants completed another set of physiological and
neuropsychological measures. Experimental participants reported significant
increases in positive symptoms resulting from the placebo stimulant. Expectancies
moderated the impact of the placebo stimulant on Passage Comprehension
performance; no other neuropsychological task performance was impacted. Despite
subjective reports of feeling the effects of stimulants, task performance was
unaffected. Moreover, expectancies may play a small role in perceptions of the
effects of stimulants.
PMID- 28699833
TI - Safety assessment of 16 sweeteners for the Korean population using dietary intake
monitoring and poundage method.
AB - A sweetener is a food additive that imparts a sweet taste to food products.
Sweeteners have been increasingly used in Korea since the approval of sodium
saccharin and d-sorbitol in 1962. Unlike food contaminants, humans are exposed to
food additives only through the consumption of processed food products. For
exposure assessments of sweeteners, the dietary intakes of food products
containing acesulfame-K, aspartame, saccharin-Na, and sucralose were determined,
and the resulting calculated estimated daily intake (EDI) values were compared
directly with each additive's ADI. The poundage method was used to calculate the
daily intake per capita for 12 additional sweeteners, such as lactitol, for which
appropriate analytical methods for food products do not exist. The risk, as
evaluated by comparing the EDI with the ADI, was determined to be 2.9% for
acesulfame-K, 0.8% for aspartame, 3.6% for saccharin-Na, 4.3% for steviol
glycosides, and 2.1% for sucralose. No hazardous effect was predicted for the
other 11 sweeteners, including lactitol.
PMID- 28699834
TI - The Concept of Recovery as Experienced by Persons with Dual Diagnosis: A
Systematic Review of Qualitative Research From a First-Person Perspective.
AB - OBJECTIVES: In recent years, the concept of recovery has gained ground in the
treatment of persons with dual diagnosis. Recovery refers to living a meaningful
life despite limitations caused by mental illness and substance use disorders. It
also implies that support for persons with dual diagnosis should be organized
according to the personal needs and wishes of its users. Therefore, it is
important to gain insight into the aspects that persons with dual diagnosis deem
important for their recovery process. This systematic review aims to summarize
existing qualitative research on the meaning of recovery from the perspective of
persons with dual diagnosis. METHODS: A literature search was conducted following
the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta
Analyses statement for systematic reviews in the following databases: Cumulative
Index to Nursing and Allied Health Literature, PsycINFO, Medline, Embase, and Web
of Science. RESULTS: Sixteen studies using a qualitative research design were
retained in which four overarching themes could be identified. The first theme
focused on feeling supported by family and peers and being able to participate in
the community. The second theme focuses on the need for a holistic and
individualized treatment approach, seeing the persons "behind the symptoms." The
third theme that emerged was having personal beliefs, such as fostering feelings
of hope, building a new sense of identity, gaining ownership over one's life, and
finding support in spirituality. The last theme identified was the importance of
meaningful activities that structure one's life and give one motivation to carry
on. CONCLUSIONS: In this review, the participants pleaded for "flexibility" in
mental health care, i.e., an approach that allows for both successes and
failures. However, in order to come to a more comprehensive theoretical model of
recovery in persons with dual diagnosis, future research is necessary to gain
insight into the underlying mechanisms of recovery processes.
PMID- 28699835
TI - Professional quality of life of adult protective service workers.
AB - Adult Protective Services (APS) workers are exposed to substantial occupational
hazards and job stress, but these stressors are underdocumented. Therefore, we
sought to describe APS workers' work environments and responses to occupational
hazards and stressors, including compassion fatigue, burnout, and secondary
traumatic stress. Survey data were gathered with closed-ended questionnaires
administered to APS workers in an urban setting. Virtually all workers (97%)
reported exposure to one or more environmental hazards in their work, and 80%
reported hazard exposure in the past month. Workers also reported mixed responses
to their work environment and to experiences with supervision. A sizable minority
(22.7%) was at high risk for burnout, 24.6% were at risk for secondary traumatic
stress, and 19.9% reported low compassion satisfaction. The results document
multiple stressors in APS work. The APS partner is committed to ongoing efforts
to better support its staff, and these findings can inform future efforts to
enhance supervisor support and worker self-care, to minimize burnout and
secondary traumatic stress.
PMID- 28699836
TI - Blogs and the Art of Dying: Blogging With, and About, Severe Cancer in Late
Modern Swedish Society.
AB - In recent years, the common and mundane dying has begun to take place in the
public space of the Internet. Among the blogs about food, fashion, travel, and
other joyful aspects of life, blogs about severe disease and dying have appeared.
The aim of this article is to describe some characteristic features of a sample
of cancer blogs and to discuss them in the light of Zygmunt Bauman's theory of
the rationalization of death in modernity and theories about networked media,
especially the theories about "affective labor" and "ambient intimacy" by
McCosker, Darcy, and Pfister. It will then be argued that an affective
communication is performed in and through these cancer blogs, where not only
language but also the deficiencies of language-and what is called shared
ineffability-might be valuable and meaningful (although not unproblematic) as
part of a late modern approach to death, and in the practicing of the art of
dying.
PMID- 28699837
TI - Scientists and religious leaders compete for cultural authority of science.
AB - Measurement of public trust in sources of information about science primarily
examines whether the public turns to the "science communication industry" for
information about science. Research posits, however, that scientists are not the
singular cultural authority on science. Here, we examine the extent to which
people turn to religion and religious individuals for information about science.
Drawing on a nationally representative survey of US adults, we examine what
factors-when individuals have a question about science-shape respondent's
likelihood of turning to science-based versus religion-based sources. Results
show that religiosity is a strong positive predictor of looking to religious
sources for scientific information, but it does not deter seeking out scientific
sources. The results also show that interest in science has a positive influence
on the likelihood of turning to a religious source.
PMID- 28699838
TI - Sageretia thea (Osbeck.) mediated synthesis of zinc oxide nanoparticles and its
biological applications.
AB - AIM: To investigate the physical and biological properties of bioinspired zinc
oxide (ZnO) nanoparticles via aqueous leaf extracts of Sageretia thea.
EXPERIMENTAL: Nanoparticles of size approximately 12.4 nm were extensively
characterized. In vitro antimicrobial, cytotoxic, biocompatible and enzyme
inhibition assays were performed. RESULTS: Significant antimicrobial activities
with and without UV illumination are reported. Bioinspired ZnO nanoparticles were
found effective against fungal strains. MTT assay was performed to check the
leishmanicidal activity against promastigotes (IC50: 6.2 MUg/ml) and amastigotes
(IC50: 10.87 MUg/ml) of Leishmania tropica. Brine shrimp lethality was also
indicated by bioinspired ZnO nanoparticles (IC50: 21.29 MUg/ml). CONCLUSION:
Hemocompatible nature of bioinspired nanoparticles was revealed. Furthermore, the
antioxidant activities were performed. In addition, significant protein kinase
while insignificant alpha amylase inhibition were recorded.
PMID- 28699839
TI - Validated low-volume immunoassay for the reliable determination of direct renin
especially valuable for pediatric investigations.
AB - INTRODUCTION: The pharmacotherapy of pediatric patients suffering from heart
failure is extrapolated from adults due to missing data in children. OBJECTIVES:
Development and validation of a low-volume immunoassay for the reliable
determination of renin. EXPERIMENTAL: The immunoassay was validated according to
international guidelines. RESULTS: The assay allows the reliable determination of
renin in 40 MUL plasma within a calibration range of 4-128 pg/mL. Between-run
accuracy varied from -3.3 to +3.0% (relative error), while between-run precision
ranged from 4.9 to 11.3% (coefficient of variation). CONCLUSION: The low-volume
immunoassay facilitates the reliable collection of pharmacodynamic data in
children.
PMID- 28699840
TI - Distributed improvisation: a systems perspective of improvisation 'epics' by led
outdoor activity leaders.
AB - Improvisation represents the spontaneous and real-time conception and execution
of a novel response to an unanticipated situation. In order to benefit from the
positive safety potential of this phenomenon, it is necessary to understand what
influences its appropriateness and effectiveness. This study has applied the
system-based methodology Impromaps to analysing accounts of improvisation aimed
at mitigating adverse safety outcomes. These accounts were obtained from led
outdoor activity (LOA) leaders through critical decision method interviews.
Influencing factors and interactions have been identified across all system
levels. The factors most influential to leaders' ability to improvise are
'Policy, procedures and rules', 'Organisation culture', 'Training', 'Role
responsibilities', 'Communication/instruction/demonstration', 'Situation
awareness', 'Leader experience', 'Mental simulation', 'Equipment, clothing & PPE'
and 'Terrain/physical environment'. To enhance the likelihood of effective,
appropriate improvisation, LOA providers are recommended to focus on higher level
factors over which they are able to exert greater control. Practitioner Summary:
To enhance resilience in safety-critical situations, organisations need to
understand what influences appropriate, effective improvisation. To elucidate
this, the Impromaps methodology is applied to in-depth interview data. The
Impromap affords a graphical depiction of the influencing factors and
interactions across the system, providing a basis for the development of
interventions.
PMID- 28699841
TI - Co-digestion of agricultural and municipal waste to produce energy and soil
amendment.
AB - In agriculture, manure and cotton gin waste are major environmental liabilities.
Likewise, grass is an important organic component of municipal waste. These
wastes were combined and used as substrates in a two-phase, pilot-scale anaerobic
digester to evaluate the potential for biogas (methane) production, waste
minimisation, and the digestate value as soil amendment. The anaerobic digestion
process did not show signs of inhibition. Biogas production increased during the
first 2 weeks of operation, when chemical oxygen demand and volatile fatty acid
concentrations and the organic loading rate to the system were high. Chemical
oxygen demand from the anaerobic columns remained relatively steady after the
first week of operation, even at high organic loading rates. The experiment
lasted about 1 month and produced 96.5 m3 of biogas (68 m3 of CH4) per tonne of
waste. In terms of chemical oxygen demand to methane conversion efficiency, the
system generated 62% of the theoretical methane production; the chemical oxygen
demand/volatile solids degradation rate was 62%, compared with the theoretical
66%. The results showed that co-digestion and subsequent digestate composting
resulted in about 60% and 75% mass and volume reductions, respectively. Digestate
analysis showed that it can be used as a high nutrient content soil amendment.
The digestate met Class A faecal coliform standards (highest quality) established
in the United States for biosolids. Digestion and subsequent composting
concentrated the digestate nitrogen, phosphorus, and potassium content by 37%,
24%, and 317%, respectively. Multi-substrate co-digestion is a practical
alternative for agricultural waste management, minimisation of landfill disposal,
and it also results in the production of valuable products.
PMID- 28699842
TI - Mean platelet volume measurements should not be used as an indicator of platelet
function.
PMID- 28699843
TI - Social workers have an obligation to all patients regarding confidentiality ...
however, for some patients, the obligation is greater.
AB - Social workers are held to many ethical obligations regarding patients including
maintaining patient confidentiality and staying up to date on confidentiality
laws, statutes, and regulations. As the landscape of health care continues to
change, including the increased use of technology to maintain patient records,
highlights this need. The changes in the regulations on confidentiality of those
who are receiving substance use treatment, 42 CFR Part 2, are presented. The
other regulations and laws covered include HIPAA, HITECH, and the ACA. This
includes the changes that have taken place, how to be compliant, and which to
follow when.
PMID- 28699844
TI - Khat Use is Associated with Tobacco, Alcohol, and Illicit Drug Use: A Cross
Sectional Examination in the United States.
AB - No study has systematically examined khat (Catha edulis) use and its linkages
with other substance use in the United States. This study provides novel findings
related to the associations of khat with other substance use among immigrants in
metropolitan areas of Minnesota where large East African communities reside.
Using a convenience sampling, a total of 261 individuals completed a brief face
to-face interview during which demographic information and substance use were
assessed. The proportion of lifetime and current use were 30% and 6.6% for khat,
35% and 18% for tobacco, 35% and 21% for alcohol, and 13% and 10% for other
illicit drugs. Self-report history of khat use was associated with tobacco,
alcohol, and other drug use. Tobacco use was related to alcohol and use of other
drugs. The results suggest that a history of khat use is useful in identifying
individuals who are vulnerable to substance-use-related problems. The findings
indicate the need for more research on khat in the U.S.
PMID- 28699845
TI - Development and implementation of an alcohol withdrawal protocol using a 5-item
scale, the Brief Alcohol Withdrawal Scale (BAWS).
AB - BACKGROUND: The standard of care for management of alcohol withdrawal is symptom
triggered treatment using the Clinical Institute Withdrawal Assessment for
Alcohol (CIWA-Ar). Many items of this 10-question scale rely on subjective
assessments of withdrawal symptoms, making it time-consuming and cumbersome to
use. Therefore, there is interest in shorter and more objective methods to assess
alcohol withdrawal symptoms. METHODS: A 6-item withdrawal scale developed at
another institution was piloted. Based on comparison with the CIWA-Ar, this was
adapted into a 5-item scale named the Brief Alcohol Withdrawal Scale (BAWS). The
BAWS was compared with the CIWA-Ar and a withdrawal protocol utilizing the BAWS
was developed. The new protocol was implemented on an inpatient unit dedicated to
treating substance withdrawal. Data was collected on the first 3 months of
implementation and compared with the 3 months prior to that. RESULTS: A BAWS
score of 3 or more predicted CIWA-Ar score >=8 with a sensitivity of 85.3% and
specificity of 65.8%. The demographics of the patients in the 2 time periods were
similar: the mean age was 45.9; 70.6% were male; 30.9% received concurrent
treatment for opioid withdrawal; and 14.2% were receiving methadone maintenance.
During the BAWS phase, patients received significantly less diazepam (mean dose
81.4 vs. 60.3 mg, P < .001). There was no significant difference in length of
stay. No patients experienced a seizure, delirium, or required transfer to a
higher level of care during any of the 664 admissions in either phase.
CONCLUSIONS: This simple protocol utilizing a 5-item withdrawal scale performed
well in this setting. Its use in other settings, particularly with patients with
concurrent medical illnesses or more severe withdrawal, needs to be explored
further.
PMID- 28699846
TI - Safety and effectiveness of tadalafil in pediatric patients with pulmonary
arterial hypertension: a sub-group analysis based on Japan post-marketing
surveillance.
AB - OBJECTIVE: To evaluate the long-term safety and effectiveness of tadalafil in
pediatric patients with pulmonary arterial hypertension (PAH) in real-world
clinical practice. METHODS: This is an observational surveillance of PAH patients
receiving tadalafil in the contracted sites. A sub-group analysis was performed
of 391 pediatric PAH patients (<18 years) who were included from 1,704 total
patients in this surveillance. Safety was assessed from the frequency of adverse
drug reactions (ADRs), discontinuations due to adverse events (AEs), and serious
adverse drug reactions (SADRs). Effectiveness measurements included change in
World Health Organization (WHO) functional classification of PAH, cardiac
catheterization (pulmonary arterial pressure: PAP), and echocardiography
(tricuspid regurgitation pressure gradient: TRPG). Survival rate was also
measured. RESULTS: The mean patient age was 5.7 +/- 5.34 years. Associated PAH
(APAH) and idiopathic PAH (IPAH) accounted for 76.0% and 17.6%, respectively, of
the PAH patients. Patients were followed for up to 2 years. Among 391 patients
analyzed for safety, the overall incidence rate of ADRs was 16.6%. The common
ADRs (>= 1%) were headache (2.8%), hepatic function abnormal, platelet count
decreased (1.3% each), and epistaxis, (1.0%). Eleven patients (2.8%) reported 16
SADRs. Three patients died secondary to SADRs. For the effectiveness analysis,
the incidence of WHO functional class improvement at 3 months, 1 year, and 2
years after the initiation of tadalafil and last observation in pediatric
patients were 16.5%, 19.7%, and 16.3%, respectively. Both PAP and TRPG showed a
statistically significant reduction at last observation. CONCLUSION: This
manuscript reveals the use of tadalafil in the real-world pediatric population
with an acceptable safety profile in Japan.
PMID- 28699847
TI - A systematic review and combined analysis of therapeutic drug monitoring studies
for long-acting risperidone.
AB - INTRODUCTION: This systematic review of therapeutic drug monitoring (TDM)
identifies three long-acting injectable (LAI) risperidone formulations. Areas
covered: Limited data is available on two formulations (RBP-7000 and in Situ
Microparticle), but 20 TDM articles on the microsphere formulation were found.
Risperidone TDM includes the serum concentrations of risperidone and its active
metabolite, 9-hydroxyrisperidone, used for calculating: 1) the risperidone/9
hydroxyrisperidone (R/9-OH-R) ratio (a measure of CYP2D6; values >1 are
indicative of a CYP2D6 poor metabolizer) and 2) the total risperidone
concentration-to-dose (C/D) ratio (a measure of risperidone clearance with a
normal value around 7 in oral risperidone). The weighted mean R/9-OH-R ratio was
0.48 (approximately twice that of oral risperidone TDM) in a combined analysis
from 329 patients in 6 risperidone LAI studies without major confounders. The
total C/D ratios from 297 patients in 6 risperidone LAI studies ranged from 7.4
to 9.7 ng/ml/mg/day with a weighted mean of 8.8 ng/ml/mg/day. Expert commentary:
Clinicians using TDM for risperidone LAI microsphere formulation need to: 1)
consider steady state to be reached >= 6 weeks after the first injection, 2) pay
attention to a) co-medications with inducers/inhibitors, b) severe
inflammations/infections, and c) hepatic/renal impairment, and 3) use Castberg's
recommendation to calculate risperidone dosing.
PMID- 28699848
TI - Impact of helmet use on traumatic brain injury from road traffic accidents in
Cambodia.
AB - OBJECTIVE: Rapid urbanization and motorization without corresponding increases in
helmet usage have made traumatic brain injury due to road traffic accidents a
major public health crisis in Cambodia. This analysis was conducted to quantify
the impact of helmets on severity of injury, neurosurgical indication, and
functional outcomes at discharge for motorcycle operators who required
hospitalization for a traumatic brain injury following a road traffic accident in
Cambodia. METHODS: The medical records of 491 motorcycle operators who presented
to a major tertiary care center in Cambodia with traumatic brain injury were
retrospectively analyzed using multivariate logistic regression. RESULTS: The
most common injuries at presentation were contusions (47.0%), epidural hematomas
(30.1%), subdural hematomas (27.9%), subarachnoid hemorrhages (12.4%), skull
fractures (21.4%), and facial fractures (18.5%). Moderate-to-severe loss of
consciousness was present in 36.3% of patients. Not wearing a helmet was
associated with an odds ratio of 2.20 (95% confidence interval [CI], 1.15-4.22)
for presenting with moderate to severe loss of consciousness compared to helmeted
patients. Craniotomy or craniectomy was indicated for evacuation of hematoma in
20.0% of cases, and nonhelmeted patients had 3.21-fold higher odds of requiring
neurosurgical intervention (95% CI, 1.25-8.27). Furthermore, lack of helmet usage
was associated with 2.72-fold higher odds of discharge with functional deficits
(95% CI, 1.14-6.49). In total, 30.1% of patients were discharged with severe
functional deficits. CONCLUSIONS: Helmets demonstrate a protective effect and may
be an effective public health intervention to significantly reduce the burden of
traumatic brain injury in Cambodia and other developing countries with increasing
rates of motorization across the world.
PMID- 28699849
TI - Protein-energy wasting significantly increases healthcare utilization and costs
among patients with chronic kidney disease: a propensity-score matched cohort
study.
AB - BACKGROUND: Disease-related malnutrition is highly prevalent, and has prognostic
implications for patients with chronic kidney disease (CKD); however, few studies
have investigated the impact of malnutrition, or protein-energy wasting (PEW), on
healthcare utilization and medical expenditure among CKD patients. METHODS: Using
claim data from the National Health Insurance in Taiwan, this study identified
patients with CKD between 2009-2013 and categorized them into those with mild,
moderate, or severe CKD. Cases with PEW after CKD was diagnosed were propensity
score matched with controls in a 1:4 ratio. Healthcare resource utilization
metrics were compared, including outpatient and emergency department visits,
frequency and duration of hospitalization, and the cumulative costs associated
with different CKD severity. RESULTS: From among 347,501 CKD patients, eligible
cohorts of 66,872 with mild CKD (49.2%), 27,122 with moderate CKD (19.9%), and
42,013 with severe CKD (30.9%) were selected. Malnourished CKD patients had
significantly higher rates of hospitalization (p < .001 for all severities) and
re-admission (p = .015 for mild CKD, p = .002 for severe CKD) than non
malnourished controls. Cumulative medical costs for outpatient and emergency
visits, and hospitalization, were significantly higher among all malnourished CKD
patients than non-malnourished ones (p < .001); total medical costs were also
higher among malnourished patients with mild (62.9%), moderate (59.6%), or severe
(43.6%) CKD compared to non-malnourished patients (p < .001). CONCLUSIONS: In a
nationally-representative cohort, CKD patients with PEW had significantly more
healthcare resource utilization and higher aggregate medical costs than those
without, across the spectrum of CKD: preventing PEW in CKD patients should
receive high priority if we would like to reduce medical costs.
PMID- 28699850
TI - The effect of balance training intervention on postural stability in children
with asthma.
AB - OBJECTIVE: Pulmonary rehabilitation is mainly focused on exercise training and
breathing retraining in children with asthma. Conversely, balance training is not
usually recommended for the treatment, although postural deficits were found in
these patients. Therefore, this study assessed the effect of balance training
intervention on postural stability in children with asthma. METHODS: Nineteen
children with mild intermittent asthma (age 11.1 +/- 2.1 years, height 147.6 +/-
13.9 cm, weight 41.8 +/- 13.3 kg) were randomly assigned to an experimental group
or a control group and completed a four-week physiotherapy program including
breathing exercises and aerobic physical training (six times/week, 45 minutes).
Both groups performed the same training, but only the experimental group
underwent exercises on balance devices. The center of pressure (CoP) velocity in
the anteroposterior (Vy) and mediolateral (Vx) directions, and total CoP velocity
(Vtot) were recorded before and after training in the preferred and the adjusted
stances under eyes open (EO) and eyes closed (EC) conditions. RESULTS: The
addition of balance intervention led to significant improvements of Vtot (p =
0.02, p = 0.04) in both types of stance, Vx in the preferred stance (p = 0.03)
and Vy in the adjusted stance (p = 0.01) under EO conditions. Significant
improvements were also found in Vy in the adjusted stance (p = 0.01) under EC
conditions. CONCLUSIONS: Results of this study support the effectiveness of
balance training as a part of physiotherapy treatment for improving balance
performance, predominantly under EO conditions, in children with mild asthma.
PMID- 28699851
TI - Dynamics of CD4 cell count among HIV-infected individuals in Lagos, Nigeria.
AB - Human immunodeficiency virus (HIV) infection leads to progressive loss of CD4 T
cells. Antiretroviral therapy has been able to inhibit this process, resulting in
significant level of immune recovery and function. Our aim is to investigate the
dynamics of CD4 recovery among HIV patients in Lagos, Nigeria. A total of 213 HIV
positive individuals were enrolled between October 2007 and May 2008, and
followed up for 9 months based on CD4 count. CD4 analysis was done by flow
cytometry at enrollment and after every 3 months. Data were grouped according to
age range, antiretroviral treatment (ART), and time between infection and
diagnosis. Kaplan-Meier survival analysis was used for data analysis. There was a
significant difference in CD4 count between antiretroviral (ART) naive and ART
experienced subjects (P < 0.001). About 50% of the ART experienced population was
identified to show poor CD4 reconstitution unable to achieve a CD4 of 500
cells/ul after 9 months of therapy. Time interval between infection and therapy
was also identified to contribute to poor CD4 restoration. Further studies need
to be done to classify immunological nonresponders among HIV patients in Nigeria.
We also recommend introduction of programs that will facilitate early detection
of HIV infection.
PMID- 28699852
TI - Children's representations of nature using photovoice and community mapping:
perspectives from South Africa.
AB - The aim of the study was to explore children's representations and perceptions of
natural spaces using photovoice and community mapping. The sample consisted of 28
children aged 12-14 years residing in urban and rural communities in the Western
Cape, South Africa. Data were collected by means of a series of six focus groups
interviews (three photovoice discussion groups and three community mapping
discussion groups). For the photovoice missions, children were provided with a 28
exposure disposable camera and given 1 week to complete their missions. Thematic
analysis was employed to analyse the data. Three key themes emerged, namely: safe
spaces in nature, unsafe spaces in nature, and children's favourite places in
nature. Socio-economic status (SES) was found to be a determining factor in how
children make sense of natural spaces. Children from low SES communities
indicated being more constricted in their mobility, and were unable to access to
safe natural spaces compared to the children from the middle SES community. It is
recommended that an expedient starting point would be to work towards and build
environmentally and child-friendly communities for children, with children as key
contributors in the planning process using a child participation framework.
PMID- 28699853
TI - FoxO4 negatively controls Tat-mediated HIV-1 transcription through the post
transcriptional suppression of Tat encoding mRNA.
AB - The connection between the repression of human immunodeficiency virus type 1(HIV
1) transcription and the resting CD4+ T cell state suggests that the host
transcription factors involved in the active maintenance of lymphocyte quiescence
are likely to repress the viral transactivator, Tat, thereby restricting HIV-1
transcription. In this study, we analysed the interplay between Tat and the
forkhead box transcription factors, FoxO1 and FoxO4. We show that FoxO1 and FoxO4
antagonize Tat-mediated transactivation of HIV-1 promoter through the repression
of Tat protein expression. No effect was observed on the expression of two HIV-1
accessory proteins, Vif and Vpr. Unexpectedly, we found that FoxO1 and FoxO4
expression causes a strong dose-dependent post-transcriptional suppression of Tat
mRNA, indicating that FoxO should effectively inhibit HIV-1 replication by
destabilizing Tat mRNA and suppressing Tat-mediated HIV-1 transcription. In
accordance with this, we observed that the Tat mRNA half-life is reduced by FoxO4
expression. The physiological relevance of our findings was validated using the J
Lat 10.6 model of latently infected cells. We demonstrated that the
overexpression of a constitutively active FoxO4-TM mutant antagonized HIV-1
transcription reactivation in response to T cell activators, such as TNF-alpha or
PMA. Altogether, our findings demonstrate that FoxO factors can control HIV-1
transcription and provide new insights into their potential role during the
establishment of HIV-1 latency.
PMID- 28699854
TI - Algibacter aquaticus sp. nov., a slightly alkaliphilic marine Flavobacterium
isolated from coastal surface water.
AB - A rod-shaped, pale yellow-pigmented, aerobic, Gram-staining-negative strain with
gliding motility, designated as strain SK-16T, was isolated from the coastal
surface water of a semi-enclosed coastal inlet in Misaki, Japan. Analysis of 16S
rRNA gene sequences revealed that SK-16T represented a member of the family
Flavobacteriaceae and was closely related to the genus Algibacter, with sequence
similarities ranging from 95.9 to 94.3 % to the type strains of species of the
genus Algibacter. The major cellular fatty acids were iso-C15 : 0, iso-C17 : 0 3
OH, iso-C15 : 0 G and iso-C15 : 0 3-OH. Major polar lipids were
phosphatidylethanolamine, an aminophospholipid and an unidentified phospholipid.
The DNA G+C content of SK-16T was 32.3 mol% and MK-6 was the only predominant
isoprenoid quinone. On the basis of the results of phenotypic, genotypic,
chemotaxonomic and phylogenetic studies, it was suggested that SK-16T represents
a novel species within the genus Algibacter, with the newly proposed name
Algibacteraquaticus. The type strain is SK-16T (=NBRC 110220T=KCTC 32974T).
PMID- 28699855
TI - Paenibacillus tritici sp. nov., isolated from wheat roots.
AB - A bacterial strain designated RTAE36T was isolated from wheat roots in northern
Spain. Phylogenetic analyses based on 16S rRNA gene sequence placed the isolate
into the genus Paenibacillus with its closest relative being Paenibacillus
borealis DSM 13188T with 97.7 % sequence similarity. Cells of the isolate were
facultatively anaerobic, Gram-stain-positive, motile and sporulating rods.
Catalase and oxidase were positive. Gelatin, casein and starch were not
hydrolysed. Growth was supported by many carbohydrates and organic acids as
carbon sources. MK-7 was the only menaquinone detected, and anteiso-C15 : 0, C16
: 0, iso-C14 : 0 and iso-C16 : 0 were the major fatty acids. The polar lipids
profile consisted of diphosphatidylglycerol, phosphatidylglycerol,
phosphatidylethanolamine, one unidentified aminolipid, two unidentified
phospholipids, three unidentified phosphoaminolipids, one unidentified glycolipid
and one unidentified lipid. meso-Diaminopimelic acid was detected in the cell
wall peptidoglycan. Strains RTAE36T and P. borealis DSM 13188T had an mean DNA
DNA relatedness of 39 % and differed in several phenotypic and chemotaxonomic
characteristics, confirming that strain RTAE36T should be considered as a
representative of a novel species of the genus Paenibacillus, for which the name
Paenibacillus tritici sp. nov. is proposed. The type strain is RTAE36T (=LMG
29502T=CECT 9125T).
PMID- 28699856
TI - Analysis of the origin of inherited chromosomally integrated human herpesvirus 6
in the Japanese population.
AB - Integration of the complete human herpesvirus 6 (HHV-6) genome into the telomere
of a chromosome has been reported in some individuals (inherited chromosomally
integrated HHV-6; iciHHV-6). Since the proportion of iciHHV-6-positive
individuals with integration in chromosome 22 is high in Japan, we hypothesized a
founder effect. In this study, we sought to elucidate the reason for the high
proportion of viral integrations into chromosome 22. We analyzed six cases of
iciHHV-6A and two cases of iciHHV-6B, including one iciHHV-6A case with a matched
sample from a father and one iciHHV-6B case with a matched sample from a mother.
In iciHHV-6A, the same copy numbers of viral telomeric repeat sequences (TRS) and
the same five microsatellite markers were detected in both the index case and
paternal sample. Moreover, the same five microsatellite markers were demonstrated
in four cases and the same copy numbers of viral TRS were demonstrated in two
pairs of two cases. The present microsatellite analysis suggested that the viral
genomes detected in some iciHHV-6A patients were derived from a common ancestral
integration.
PMID- 28699857
TI - Differences in the growth properties of Zika virus foetal brain isolate and
related epidemic strains in vitro.
AB - Zika virus (ZIKV) has recently emerged into new areas in the Americas and Asia,
causing an epidemic characterized by severe congenital infections. While ZIKV
infection is usually asymptomatic or causes mild symptoms, it has now caused a
high rate of foetal brain and ocular abnormalities. The underlying reasons for
the varying severity of disease outcomes is poorly understood. In this study, we
compared the infectivity and replication of three disease-associated Zika viruses
of Asian lineage, as well as the prototypic ZIKV strain from Africa. The recent
foetal brain isolate FB-GWUH-2016 demonstrated enhanced infectivity and
replication over the serum-origin isolates from French Polynesia and Martinique,
suggesting differences in the pathogenic properties.
PMID- 28699858
TI - Bovine lactoferrin activity against Chikungunya and Zika viruses.
AB - Chikungunya (CHIKV) and Zika (ZIKV) viruses are arboviruses which have recently
broken their sylvatic isolation and gone on to spread rampantly among humans in
some urban areas of the world, especially in Latin America. Given the lack of
effective interventions against such viruses, the aim of this work was to
evaluate the antiviral potential of bovine lactoferrin (bLf) in their infections.
Through viability, plaque, immunofluorescence and nucleic acid quantification
assays, our data show that bLf exerts a dose-dependent strong inhibitory effect
on the infection of Vero cells by the aforementioned arboviruses, reducing their
infection efficiency by up to nearly 80 %, with no expressive cytotoxicity, and
that such antiviral activity occurs at the levels of input and output of virus
particles. These findings reveal that bLf antimicrobial properties are extendable
to CHIKV and ZIKV, underlining a generic inhibition mechanism that can be
explored to develop a potential strategy against their infections.
PMID- 28699859
TI - Understanding the role of microRNAs in the interaction of Aedes aegypti
mosquitoes with an insect-specific flavivirus.
AB - The Flavivirus genus contains some of the most prevalent vector-borne viruses,
such as the dengue, Zika and yellow fever viruses that cause devastating diseases
in humans. However, the insect-specific clade of flaviviruses is restricted to
mosquito hosts, albeit they have retained the general features of the genus, such
as genome structure and replication. The interactions between insect-specific
flaviviruses (ISFs) and their mosquito hosts are largely unknown. Pathogenic
flaviviruses are known to modulate host-derived microRNAs (miRNAs), a class of
non-coding RNAs that are important in controlling gene expression. Alterations in
miRNAs may represent changes in host gene expression and promote understanding of
virus-host interactions. The role of miRNAs in ISF-mosquito interactions is
largely unknown. A recently discovered Australian ISF, Palm Creek virus (PCV),
has the ability to suppress medically relevant flaviviruses. Here, we
investigated the potential involvement of miRNAs in PCV infection using the model
mosquito Aedes aegypti. By combining small-RNA sequencing and bioinformatics
analysis, differentially expressed miRNAs were determined. Our results indicated
that PCV infection hardly affects host miRNAs. Out of 101 reported miRNAs of Ae.
aegypti, only aae-miR-2940-5p had a significantly altered expression over the
course of infection. However, further analysis of aae-miR-2940-5p revealed that
this miRNA does not have any direct impact on PCV replication in vitro. Thus,
overall the results suggest that PCV infection has a limited effect on the
mosquito miRNA profile and therefore miRNAs may not play a significant role in
the PCV-Ae. aegypti interaction.
PMID- 28699860
TI - Leucobacter corticis sp. nov., isolated from symptomatic bark of Populus *
euramericana canker.
AB - A Gram-stain-positive, aerobic, non-motile, rod-shaped bacterial strain,
designated 2C-7T, was isolated from symptomatic bark of a Populus * euramericana
canker. Growth occurred between 10 and 37 degrees C and between pH 6 and 10,
with optimal growth at 30 degrees C and pH 7.0-8.0. Growth was present under 0-8
% (w/v) salinity conditions (optimum 1-2 %). Growth occurred in the presence of
10 mM chromium (Cr6+). The major fatty acids (>=10 %) of the novel strain were
anteiso-C15 : 0, anteiso-C17 : 0 and iso-C16 : 0. The polar lipids were
diphosphatidylglycerol, phosphatidylglycerol, phospholipid, glycolipid and two
unknown lipids. The major respiratory quinone was menaquinone MK-11. The cell
wall amino acids were 2,4-diaminobutyric acid, alanine, glutamic acid and
glycine. Strain 2C-7T was most similar to Leucobacter celer subsp. celer NAL101T
(97.2 % 16S rRNA gene sequence similarity), 'Leucobacter kyeonggiensis' F3-P9T
(97.1 %) and Leucobacter chromiireducens L-1T (97.1 %). In the phylogenetic tree,
the isolate formed a single distinct branch separate from those of L. celer
subsp. celer NAL101T, 'L. kyeonggiensis' F3-P9T and Leucobacter chironomi DSM
19883T. The DNA-DNA hybridization values between the novel strain and the
reference strains were lower than the accepted bacterial threshold level of 70 %
for species delineation. The DNA G+C content of strain 2C-7T was 70.0 mol%. Based
on the data, strain 2C-7T represents a novel species in the genus Leucobacter,
for which the name Leucobacter corticis sp. nov. is proposed. The type strain is
2C-7T (=CFCC 11901T=KCTC 39643T).
PMID- 28699861
TI - Olleya algicola sp. nov., a marine bacterium isolated from the green alga Ulva
fenestrata.
AB - A strictly aerobic, Gram-stain-negative, rod-shaped, motile by gliding and yellow
pigmented bacterium, designated strain 3Alg 18T, was isolated from the Pacific
green alga Ulva fenestrata. Phylogenetic analysis based on 16S rRNA gene
sequences showed that the novel strain was affiliated to the family
Flavobacteriaceae of the phylum Bacteroidetes, being most closely related to the
type strains of recognized species of the genus Olleya, with 16S rRNA gene
sequence similarity of 97.9-99.3 %. Strain 3Alg 18T grew in the presence of 0.5-5
% (w/v) NaCl and at 4-37 degrees C, and hydrolysed aesculin, casein, gelatin,
starch and Tweens 20, 40 and 80. The prevalent fatty acids were iso-C15 : 0, iso
C15 : 1 G, iso-C15 : 0 3-OH, iso-C16:0 2-OH, iso-C17 : 0 3-OH, summed feature 3,
iso-C16 : 0 3-OH, anteiso-C15 : 0 and C15 : 0. The polar lipid profile contained
phosphatidylethanolamine, three unidentified aminolipids and four unidentified
lipids. The major respiratory quinone was menaquinone MK-6. The genomic DNA G+C
content was 34.6 mol%. On the basis of 16S rRNA gene sequence data, and
chemotaxonomic and phenotypic characteristics, strain 3Alg 18T represents a novel
species of the genus Olleya, for which the name Olleya algicola sp. nov. is
proposed. The type strain is 3Alg 18T (=KCTC 22024T=KMM 6133T).
PMID- 28699862
TI - Lentzea cavernae sp. nov., an actinobacterium isolated from a karst cave sample,
and emended description of the genus Lentzea.
AB - A novel actinobacterial strain, designated SYSU K10001T, was isolated from a
limestone sample collected from a karst cave in Xingyi county, Guizhou province,
south-western China. The taxonomic position of the strain was investigated using
a polyphasic approach. Cells of the strain were aerobic and Gram-stain-positive.
On the basis of 16S rRNA gene sequence analysis, strain SYSU K10001T was most
closely related to the type strains of the genus Lentzea, Lentzea albida NBRC
16102T (98.8 % similarity) and Lentzea waywayandensis NRRL B-16159T (98.6 %), and
is therefore considered to represent a member of the genus Lentzea. DNA-DNA
hybridization values between strain SYSU K10001T and related type strains of the
genus Lentzea were less than 70 %. In addition, meso-diaminopimelic acid was the
diagnostic diamino acid in the cell-wall peptidoglycan. The whole-cell sugars
were arabinose, fructose, mannose and xylose. The major isoprenoid quinone was MK
9(H4), while the major fatty acids (>10 %) were iso-C16 : 0 and C14 : 0. The
polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, hydroxy
phosphatidylethanolamine, phosphatidylinositol, phosphatidylinositol mannoside,
one unidentified phospholipid and one unidentified lipid. The genomic DNA G+C
content of strain SYSU K10001T was 69.4 mol%. On the basis of phenotypic,
genotypic and phylogenetic data, strain SYSU K10001T represents a novel species
of the genus Lentzea, for which the name Lentzea cavernae sp. nov. is proposed.
The type strain is SYSU K10001T (=KCTC 39804T=CGMCC 4.7367T=NBRC 112394T).
PMID- 28699863
TI - Parapedobacter deserti sp. nov., an endophytic bacterium isolated from Haloxylon
ammodendron stems.
AB - Strain N5SSJ16T, a Gram-negative-staining, non-spore-forming, rod-shaped, non
motile bacterium, was isolated from Haloxylon ammodendron stems. The strain grew
in the presence of 0-4 % (w/v) NaCl (optimum growth in the absence of NaCl), at
pH 7-9 (optimum: pH 8) and at 12-50 degrees C. Phylogenetic analysis based on
16S rRNA gene sequences showed that strain N5SSJ16T was related phylogenetically
to Parapedobacter composti 4M40T (96.5 %) and Parapedobacter luteus 4M29T (95.9
%). The cellular fatty acids were iso-C15 : 0, summed feature 3 (C16 : 1omega7c
and/or C16 : 1omega6c), summed feature 9 (C16 : 0 10-methyl and/or iso-C17 :
1omega9c) and iso-C17 : 0 3-OH. MK-7 was the respiratory quinone. The main polar
lipids were phosphatidylethanolamine, unidentified aminophospholipid and two
unknown lipids. The G+C content of the DNA was 45.8 mol%. On the basis of
chemotaxonomic, phylogenetic and phenotypic evidence, strain N5SSJ16T represents
a novel species of the genus Parapedobacter, for which the name Parapedobacter
deserti sp. nov. is proposed. The type strain is N5SSJ16T (=ACCC 19928T=KCTC
52416T).
PMID- 28699864
TI - The predominant circular form of avocado sunblotch viroid accumulates in planta
as a free RNA adopting a rod-shaped secondary structure unprotected by tightly
bound host proteins.
AB - Avocado sunblotch viroid (ASBVd), the type member of the family Avsunviroidae,
replicates and accumulates in chloroplasts. Whether this minimal non-protein
coding circular RNA of 246-250 nt exists in vivo as a free nucleic acid or
closely associated with host proteins remains unknown. To tackle this issue, the
secondary structures of the monomeric circular (mc) (+) and (-) strands of ASBVd
have been examined in silico by searching those of minimal free energy, and in
vitro at single-nucleotide resolution by selective 2'-hydroxyl acylation analysed
by primer extension (SHAPE). Both approaches resulted in predominant rod-like
secondary structures without tertiary interactions, with the mc (+) RNA being
more compact than its (-) counterpart as revealed by non-denaturing polyacryamide
gel electrophoresis. Moreover, in vivo SHAPE showed that the mc ASBVd (+) form
accumulates in avocado leaves as a free RNA adopting a similar rod-shaped
conformation unprotected by tightly bound host proteins. Hence, the mc ASBVd (+)
RNA behaves in planta like the previously studied mc (+) RNA of potato spindle
tuber viroid, the type member of nuclear viroids (family Pospiviroidae),
indicating that two different viroids replicating and accumulating in distinct
subcellular compartments, have converged into a common structural solution.
Circularity and compact secondary structures confer to these RNAs, and probably
to all viroids, the intrinsic stability needed to survive in their natural
habitats. However, in vivo SHAPE has not revealed the (possibly transient or
loose) interactions of the mc ASBVd (+) RNA with two host proteins observed
previously by UV irradiation of infected avocado leaves.
PMID- 28699865
TI - Phaeobacter porticola sp. nov., an antibiotic-producing bacterium isolated from a
sea harbour.
AB - Three heterotrophic, aerobic, brown-pigmented strains, designated P97T, P100 and
P104, were isolated from a harbour in the southern North Sea. Phylogenetic
analysis of 16S rRNA gene sequences revealed that the isolates are affiliated to
the genus Phaeobacter. In silico DNA-DNA hybridization of the genome of strain
P97T against those of existing type species indicated that P97T represents a
novel species within the genus Phaeobacter, with Phaeobacter inhibens T5T as the
closest described organism (29.6 % DNA-DNA relatedness) followed by P.
gallaeciensis CIP 105210T (26.4 %). DNA-DNA hybridization demonstrated that the
three new strains belong to the same species. The new isolates inhibited
Pseudoalteromonas tunicata DSM 14096T, and were Gram-stain-negative, catalase-
and oxidase-positive, chemo-organoheterotrophic and motile. Growth occurred at pH
6.5-9.5 (optimum 7.0-8.0) and at 4-30 degrees C (optimum 20-28 degrees C). The
strains required NaCl for growth. The salinity range was 0.5-6.0 % (w/v) NaCl for
P97T and P100, and 0.5-5.0 % for P104, lower than values described for
Phaeobacter gallaeciensis and Phaeobacter inhibens. The optimum NaCl
concentration for strains P97T and P104 was 2.0-4.0 %, and for P100 was 2.0-3.0
%. Fatty acids (>1 %) comprised 18 : 1omega7c, 16 : 0, 18 : 1 omega7c 11-methyl,
18 : 0, 12 :1, 18 : 2omega7c,12, 10 : 0 3-OH and 12 : 0 3-OH. Polar lipids were
phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol, an
aminolipid, one unknown lipid and one additional unknown lipid in strain P97T.
The major respiratory quinone was Q10. Based on phylogenetic and phenotypic
differences, the strains represent a novel species in the genus Phaeobacter, for
which the name Phaeobacter porticola sp. nov. is proposed. The type strain is
P97T (=DSM 103148T=LMG 29594T).
PMID- 28699866
TI - Description of Lysinibacillus telephonicus sp. nov., isolated from the screen of
a cellular phone.
AB - A novel bacterial strain, designated S5H2222T, was isolated form the screen of a
cellular phone. The cells were Gram-stain-positive, rod-shaped, aerobic and
motile, and endospores are formed. S5H2222T grew as pale white colonies on
trypticase soy agar and the best growth was observed at 37 degrees C (10-55
degrees C) and at pH 7.0 (5.0-9.0). S5H2222T could tolerate up to 10 % (w/v)
NaCl. Phylogenetic analysis based on 16S rRNA gene sequences placed this strain
within the genus Lysinibacillus and it exhibited high 16S rRNA gene sequence
similarity to Lysinibacillus halotolerans LAM612T (97.8 %), Lysinibacillus
chungkukjangi 2RL3-2T (97.4 %) and Lysinibacillus sinduriensis BLB-1T (97.2 %).
The DNA-DNA relatedness of the strain with L. halotolerans JCM 19611T, L.
chungkukjangi KACC 16626T and L. sinduriensis KACC 16611T was 57, 64 and 55 %
respectively. The genomic DNA G+C content was 39.8 mol%. The major fatty acids of
S5H2222T were iso-C15 : 0, anteiso-C15 : 0, iso-C16 : 0 and anteiso-C17 : 0. MK-7
was the only menaquinone and the main polar lipids were diphosphatidylglycerol,
phosphatidylglycerol and phosphatidylethanolamine, four unidentified polar lipids
were also present. The diagnostic amino acids in the cell wall peptidoglycan
contained Lys-Asp (type A4alpha). On the basis of the results of the phenotypic
and genotypic characterizations, it was concluded that S5H2222T represents a
novel species of the genus Lysinibacillus, for which the name Lysinibacillus
telephonicus sp. nov. is proposed. The type strain is S5H2222T (=MCC 3065T=KACC
18714T=LMG 29294T).
PMID- 28699867
TI - Sporolactobacillus shoreicorticis sp.nov., a lactic acid-producing bacterium
isolated from tree bark.
AB - A Gram-stain-positive, lactic acid-producing bacterium designed strain MK21-7T,
was isolated from tree bark collected from the north east of Thailand. This
strain was a facultatively anaerobic spore-forming rod that was catalase
negative. It contained meso-diaminopimelic acid in the cell wall peptidoglycan
and had seven isoprene units (MK-7) as the predominant menaquinone. Major fatty
acids of MK21-7T were anteiso-C17 : 0, iso-C16 : 0, anteiso-C15 : 0 and C18 :
1omega9c. Polar lipids were phosphatidglycerol, diphosphatidylglycerol, an
unknown phospholipid, three unknown glycolipids and an unknown lipid. The results
of 16S rRNA gene sequence analysis indicated that it represented a member of the
genus Sporolactobacillus. MK21-7T showed the highest 16S rRNA gene sequence
similarity to Sporolactobacillus terrae NBRC 101527T with 98.4 % similarity and
exhibited 97.6 % similarity with Sporolactobacillus kofuensis NRIC 0334T, 97.5 %
with Sporolactobacillus laevolacticus NRIC 0361T, 97.3 % with Sporolactobacillus
nakayamaesubsp.nakayamae NRIC 0347T and 97.1 % with Sporolactobacillus
nakayamaesubsp.racemicus NBRC 101524T. Analysis of the phylogenetic relationship
based on 16S rRNA and gyrB gene sequencing revealed that the position of MK21-7T
was clearly separated from all related species of the genus Sporolactobacillus.
It had low DNA-DNA relatedness (22.8-57.2 %) with S. terrae NBRC 101527T and
related type strains. The DNA G+C content was 43.1 mol%. On the basis of the
results of the phenotypic, genotypic and chemotaxonomic studies, MK21-7T should
be classified as representing a novel species of the genus Sporolactobacillus for
which the name Sporolactobacillus shoreicorticis sp. nov. is proposed. The type
strain is MK21-7T (=NBRC 111517T=LMG 29111T=TISTR 2466T).
PMID- 28699868
TI - Flaviramulus aestuariivivens sp. nov., isolated from a tidal flat.
AB - A Gram-stain-negative, non-flagellated, non-gliding, aerobic and ovoid or rod
shaped bacterium, designated OITF-51T, was isolated from a tidal flat in Oido, an
island of South Korea, and subjected to a polyphasic taxonomic study. Strain OITF
51T grew optimally at 30 degrees C, at pH 7.0-8.0 and in the presence of 2.0 %
(w/v) NaCl. The neighbour-joining phylogenetic tree based on 16S rRNA gene
sequences revealed that strain OITF-51T forms a cluster with the type strains of
three species of the genus Flaviramulus. Strain OITF-51T exhibited 16S rRNA gene
sequence similarity values of 97.0, 95.8 and 95.8 % to the type strains of
Flaviramulus ichthyoenteri, Flaviramulus basaltis and Flaviramulus aquimarinus,
respectively, and of less than 96.5 % to the type strains of other recognized
species. Strain OITF-51T contained MK-6 as the predominant menaquinone and iso
C15 : 1 G, iso-C15 : 0, iso-C15 : 0 3-OH and iso-C17 : 0 3-OH as the major fatty
acids. The major polar lipids detected in strain OITF-51T were
phosphatidylethanolamine and one unidentified lipid. The DNA G+C content of
strain OITF-51T was 33.4 mol%, and its mean DNA-DNA relatedness value with the
type strain of F. ichthyoenteri was 13 %. Differential phenotypic properties,
together with its phylogenetic and genetic distinctiveness, revealed that strain
OITF-51T is separated from recognized species of the genus Flaviramulus. On the
basis of the data presented, strain OITF-51T is considered to represent a novel
species of the genus Flaviramulus, for which the name Flaviramulus
aestuariivivens sp. nov. is proposed. The type strain is OITF-51T (=KCTC
52657T=NBRC 112707T).
PMID- 28699869
TI - Hepatitis C virus in vitro replication is efficiently inhibited by acridone Fac4.
AB - Hepatitis C virus (HCV) affects about 170 million people worldwide. The current
treatment has a high cost and variable response rates according to the virus
genotype. Acridones, a group of compounds extracted from natural sources, showed
potential antiviral actions against HCV. Thus, this study aimed to evaluate the
effect of a panel of 14 synthetic acridones on the HCV life cycle. The compounds
were screened using an Huh7.5 cell line stably harbouring the HCV genotype 2a
subgenomic replicon SGR-Feo-JFH-1. Cells were incubated in the presence or
absence of compounds for 72 h and cell viability and replication levels were
assessed by MTT and luciferase assays, respectively. At a concentration of 5 uM
the acridone Fac4 exhibited a >90 % inhibition of HCV replication with no effect
on cell viability. The effects of Fac4 on virus replication, entry and release
steps were evaluated in Huh7.5 cells infected with the JFH-1 isolate of HCV
(HCVcc). Fac4 inhibited JFH-1 replication to approximately 70 %, while no effect
was observed on virus entry. The antiviral activity of Fac4 was also observed on
viral release, with almost 80 % of inhibition. No inhibitory effect was observed
against genotype 3 replication. Fac4 was able to intercalate into dsRNA, however
did not inhibit NS5B polymerase activity or translation driven by the HCV IRES.
Although its mode of action is partly understood, Fac4 presents significant
inhibition of HCV replication and can therefore be considered as a candidate for
the development of a future anti-HCV treatment.
PMID- 28699870
TI - MicroRNA miR-214 inhibits snakehead vesiculovirus replication by targeting the
coding regions of viral N and P.
AB - Snakeheadvesiculovirus (SHVV), a new member of the family Rhabdoviridae, has
caused enormous economic losses in snakehead fish culture during the past years
in China; however, little is known about the molecular mechanisms of its
pathogenicity. MicroRNAs (miRNAs) are small non-coding RNAs that play important
roles in virus infection. In this study, we identified that SHVV infection
downregulated miR-214 in striped snakehead (SSN-1) cells in a time- and dose
dependent manner. Notably, transfecting SSN-1 cells with miR-214 mimic
significantly inhibitedSHVV replication, whereas miR-214 inhibitor promoted it,
suggesting that miR-214 acted as a negative regulator of SHVV replication. Our
study further demonstrated that N and P of SHVV were the target genes of miR-214.
Over-expression of P, but not N, inhibited IFN-alpha production in SHVV-infected
cells, which could be restored by over-expression of miR-214. Taken together,
these results suggest that miR-214 is downregulated during SHVV infection, and
the downregulated miR-214 in turn increased N and P expression and decreased IFN
alpha production, thus facilitating SHVV replication. This study provides a
better understanding of the molecular mechanisms on the pathogenesis of SHVV and
a potential antiviral strategy against SHVV infection.
PMID- 28699871
TI - Two-component system CbrA/CbrB controls alginate production in Azotobacter
vinelandii.
AB - Azotobacter vinelandii, belonging to the Pseudomonadaceae family, is a free
living bacterium that has been considered to be a good source for the production
of bacterial polymers such as alginate. In A. vinelandii the synthesis of this
polymer is regulated by the Gac/Rsm post-transcriptional regulatory system, in
which the RsmA protein binds to the mRNA of the biosynthetic algD gene,
inhibiting translation. In several Pseudomonas spp. the two-component system
CbrA/CbrB has been described to control a variety of metabolic and behavioural
traits needed for adaptation to changing environmental conditions. In this work,
we show that the A. vinelandii CbrA/CbrB two-component system negatively affects
alginate synthesis, a function that has not been described in Pseudomonas
aeruginosa or any other Pseudomonas species. CbrA/CbrB was found to control the
expression of some alginate biosynthetic genes, mainly algD translation. In
agreement with this result, the CbrA/CbrB system was necessary for optimal rsmA
expression levels. CbrA/CbrB was also required for maximum accumulation of the
sigma factor RpoS. This last effect could explain the positive effect of
CbrA/CbrB on rsmA expression, as we also showed that one of the promoters driving
rsmA transcription was RpoS-dependent. However, although inactivation of rpoS
increased alginate production by almost 100 %, a cbrA mutation increased the
synthesis of this polymer by up to 500 %, implying the existence of additional
CbrA/CbrB regulatory pathways for the control of alginate production. The control
exerted by CbrA/CbrB on the expression of the RsmA protein indicates the central
role of this system in regulating carbon metabolism in A. vinelandii.
PMID- 28699872
TI - In vitro synergistic effects of a short cationic peptide and clinically used
antibiotics against drug-resistant isolates of Brucella melitensis.
AB - PURPOSE: In the last few decades, increasing microbial resistance to common
antibiotics has attracted researchers' attention to the development of new
classes of antibiotics such as antimicrobial peptides. Accordingly, the aim of
the current study was to evaluate antimicrobial effects of the CM11 peptide alone
and combined with common antibiotics against drug-resistant isolates of Brucella
melitensis. METHODOLOGY: A total of 50 pathogenic samples of B. melitensis were
isolated from patients and their antibiotic susceptibility pattern was evaluated
by E-test. Then, the synergistic reaction of the peptide with selected
antibiotics was evaluated using a chequerboard procedure. RESULTS: Based on the
susceptibility pattern of isolates, ciprofloxacin, rifampin, streptomycin and co
trimoxazole were used for synergistic study. According to the results, synergic
effect was observed for streptomycin and co-trimoxazole in combination with the
peptide while ciprofloxacin and rifampin showed partial synergy and additive
effect, respectively. Consistent with these results, in the time-killing assay, a
decrease in colony counts for streptomycin-peptide and co-trimoxazole-peptide was
>2 Log10 while for ciprofloxacin-peptide and rifampin-peptide it was about 1.5
Log10 and <2 Log10, which represents synergy, partial synergy and additive
interaction, respectively. CONCLUSION: These results showed that by antibiotic
CM11 combination, their effective dose can be reduced particularly for drug
resistant isolates. In conclusion, considering the importance of brucellosis
caused by B. melitensis in the Middle East beside reports on antibiotic
resistance strains, especially against rifampin, which may literally lead to an
increase in resistant strains of Mycobacterium tuberculosis in endemic areas, our
findings can be used to develop a suitable alternative treatment for brucellosis,
and with less risk.
PMID- 28699873
TI - Rhizobium zeae sp. nov., isolated from maize (Zea mays L.) roots.
AB - A bacterial strain designated CRZM18RT was isolated from a root of Zea mays in
Spain. The analysis of the 16S rRNA gene sequence showed that this strain belongs
to the genus Rhizobium, with Rhizobium cellulosilyticum ALA10B2T and Rhizobium
yantingense H66T being the most closely related species with 98.3 and 97.9 %
sequence similarity, respectively. The analysis of the concatenated recA and atpD
genes showed that strain CRZM18RT forms a cluster with these species and also
with Rhizobiumsmilacinae PTYR-5T, but the recA and atpD genes of strain CRZM18RT
were phylogenetically distant, with identities lower than 90 and 96 %,
respectively. DNA-DNA hybridization analysis showed mean relatedness of 43, 22
and 38 % with respect to R. cellulosilyticum ALA10B2T, R. yantingense LMG 28229T
and R. smilacinae LMG 27604T. Phenotypic characteristics also differed from those
of the most closely related species of the genus Rhizobium. The major fatty acids
were those from summed feature 8 (C18 : 1omega6c/C18 : 1omega7c) and C16 : 0.
Based on the genotypic, chemotaxonomic and phenotypic data obtained in this
study, we propose to classify strain CRZM18RT in a novel species named Rhizobium
zeae sp. nov. (type strain CRZM18RT=LMG 29735T=CECT 9169T).
PMID- 28699874
TI - Algoriphagus marinus sp. nov., isolated from marine sediment and emended
description of the genus Algoriphagus.
AB - A Gram-stain-negative, facultatively anaerobic coccobacilli approximately 0.4
0.5*0.5-1.1 um, non-motile, orange-pigmented bacterial strain, designated am2T,
was isolated from the coastal area of Weihai, PR China (121 degrees 57' E, 37
degrees 29' N). The temperature, pH and NaCl ranges for growth were 4-40
degrees C, pH 6.5-8.5 and 0.0-6.0 % (w/v) NaCl. The results of phylogenetic
analyses based on 16S rRNA gene sequences revealed that am2T was phylogenetically
related to members of the genus Algoriphagus and was closely related to
Algoriphagus boritolerans, Algoriphagus namhaensis and Algoriphagus antarcticus
with 96.4, 96.2 and 95.8 % sequence similarities, respectively. The quinone
system contained menaquinone MK-7 as the predominant component. The dominant
fatty acids were iso-C17 : 1omega9c,iso-C16 : 1H and iso-C15 : 0. The major polar
lipids consisted of one phospholipid, phosphatidylethanolamine and six unknown
lipids. The DNA G+C content was 40.6 mol%. On the basis of morphological,
physiological and molecular properties as well as on phylogenetic
distinctiveness, am2T should be placed into the genus Algoriphagus as a novel
species, for which the name Algoriphagus marinus sp. nov. is proposed. The type
strain is am2T (=KCTC 52549T=MCCC 1H00178T).
PMID- 28699875
TI - The middle half genome of interferon-inducing porcine reproductive and
respiratory syndrome virus strain A2MC2 is essential for interferon induction.
AB - Porcine reproductive and respiratory syndrome virus (PRRSV) is known to
antagonize the innate immune response. An atypical PRRSV strain A2MC2 is capable
of inducing synthesis of type I interferons (IFNs) in cultured cells. Here, we
show that the middle half of the A2MC2 genome is needed for triggering the IFN
synthesis. First, a cDNA infectious clone of this atypical strain was constructed
as a DNA-launched version. Virus recovery was achieved from the infectious clone
and the recovered virus, rA2MC2, was characterized. The rA2MC2 retained the
feature of IFN induction in cultured cells. Infection of pigs with the rA2MC2
virus caused viremia similar to that of the wild-type virus. Chimeric infectious
clones were constructed by swapping genomic fragments with a cDNA clone of a
moderately virulent strain VR-2385 that antagonizes IFN induction. Analysis of
the rescued chimeric viruses demonstrated that the middle two fragments, ranging
from nt4545 to nt12709 of the A2MC2 genome, were needed for the IFN induction,
whereas the chimeric viruses containing any one of the two A2MC2 fragments failed
to do so. The results and the cDNA infectious clone of the IFN-inducing A2MC2
will facilitate further study of its biology, ultimately leading towards the
development of an improved vaccine against PRRS.
PMID- 28699876
TI - Characterization of Vsr endonucleases from Neisseria meningitidis.
AB - DNA methylation is a common modification occurring in all living organisms. 5
methylcytosine, which is produced in a reaction catalysed by C5
methyltransferases, can spontaneously undergo deamination to thymine, leading to
the formation of T:G mismatches and C->T transitions. In Escherichia coli K-12,
such mismatches are corrected by the Very Short Patch (VSP) repair system, with
Vsr endonuclease as the key enzyme. Neisseria meningitidis possesses genes that
encode DNA methyltransferases, including C5-methyltransferases. We report on the
mutagenic potential of the meningococcal C5-methyltransferases M.NmeDI and
M.NmeAI resulting from deamination of 5-methylcytosine. N. meningitidis strains
also possess genes encoding potential Vsr endonucleases. Phylogenetic analysis of
meningococcal Vsr endonucleases indicates that they belong to two
phylogenetically distinct groups (type I or type II Vsr endonucleases). N.
meningitidis serogroup C (FAM18) is a representative of meningococcal strains
that carry two Vsr endonuclease genes (V.Nme18IIP and V.Nme18VIP). The V.Nme18VIP
(type II) endonuclease cut DNA containing T:G mismatches in all tested nucleotide
contexts. V.Nme18IIP (type I) is not active in vitro, but the change of Tyr69 to
His69 in the amino acid sequence of the protein restores its endonucleolytic
activity. The presence of tyrosine in position 69 is a characteristic feature of
type I meningococcal Vsr proteins, while type II Vsr endonucleases possess His69.
In addition to the T:G mismatches, V.Nme18VIP and V.Nme18IIPY69H recognize and
digest DNA with T:T or U:G mispairs. Thus, for the first time, we demonstrate
that the VSP repair system may have a wider significance and broader substrate
specificity than DNA lesions that only result from 5-methylcytosine deamination.
PMID- 28699877
TI - Isolation and characterization of Kingella negevensis sp. nov., a novel Kingella
species detected in a healthy paediatric population.
AB - We herein report the isolation and characterization of 21 Gram-stain-negative
strains cultivated from the oropharynx of healthy children in Israel and
Switzerland. Initially described as small colony variants of Kingella kingae,
phenotypic analysis, biochemical analysis, phylogenetic analysis based on
sequencing of the partial 16S rRNA gene and five housekeeping genes (abcZ, adk,
G6PD, groEL and recA), and whole genome sequencing and comparison between members
of the genera Kingella and Neisseria provided evidence for assigning them to the
genus Kingella. Cellular fatty acids included important amounts of C12 : 0, C14 :
0, C16 : 0 and C16 : 1n7. Digital DNA-DNA hybridization between the isolates
Sch538T and K. kingae ATCC 23330T revealed relatedness of 19.9 %. Comparative
analysis of 16S rRNA gene sequences available in GenBank allowed matches to
strains isolated in the USA, suggesting a wider geographical distribution. A
novel species named Kingella negevensis sp. nov. is proposed, as most strains
have been isolated in the Negev, a desert region of southern Israel. The type
strain is Sch538T (=CCUG 69806T=CSUR P957).
PMID- 28699878
TI - Genetically stable infectious Schmallenberg virus persists in foetal envelopes of
pregnant ewes.
AB - Schmallenberg virus (SBV) is a recently emerged vector-borne virus, inducing
congenital defects in bovines, ovines and caprines. Here we have shown that
infectious SBV is capable of persisting until the moment of birth in the foetal
envelopes of ewes infected with SBV-infectious serum at day 45 (1/5 positive) and
60 (4/6 positive) of gestation. This persistence of at least 100 days is a new
aspect of the SBV pathogenesis that could help to explain how SBV overwinters the
cold season in temperate climate zones. Furthermore, sequencing of the M segment
shows that the persisting virus in the foetal envelopes is genetically stable
since only a few mutations compared to the inoculum were found. This supports the
hypothesis that persisting virus could start the infection of new hosts. Finally,
neutralization tests showed that infectious SBV present in the foetal envelopes
at birth can be neutralized by the humoral immunity present in the infected ewes.
PMID- 28699879
TI - D-methionine interferes with non-typeable Haemophilus influenzae peptidoglycan
synthesis during growth and biofilm formation.
AB - Non-typeable Haemophilus influenzae (NTHi) is an opportunistic pathogen that
plays a major role in a number of respiratory tract infections, including otitis
media, cystic fibrosis and chronic obstructive pulmonary disease. Biofilm
formation has been implicated in both NTHi colonization and disease, and is
responsible for the increased tolerance of this pathogen towards antibiotic
treatment. Targeting metabolic pathways that are important in NTHi biofilm
formation represents a potential strategy to combat this antibiotic
recalcitrance. A previous investigation demonstrated increased expression of a
putative d-methionine uptake protein following exposure of NTHi biofilms to the
ubiquitous signalling molecule, nitric oxide. We therefore hypothesized that
treatment with exogenous d-methionine would impact on NTHi biofilm formation and
increase antibiotic sensitivity. Treatment of NTHi during the process of biofilm
formation resulted in a reduction in biofilm viability, increased biomass,
changes in the overall biofilm architecture and the adoption of an amorphous
cellular morphology. Quantitative proteomic analyses identified 124 proteins that
were differentially expressed following d-methionine treatment, of which 51 (41
%) were involved in metabolic and transport processes. Nine proteins involved in
peptidoglycan synthesis and cell division showed significantly increased
expression. Furthermore, d-methionine treatment augmented the efficacy of
azithromycin treatment and highlighted the potential of d-methionine as an
adjunctive therapeutic approach for NTHi biofilm-associated infections.
PMID- 28699880
TI - Paenibacillus konkukensis sp. nov., isolated from animal feed.
AB - A Gram-stain-positive, oxidase- and catalase-positive, aerobic, rod-shaped
bacterium, designated strain SK-3146T, was isolated from animal feed.
Phylogenetic analysis, based on 16S rRNA gene sequence comparisons, revealed that
the strain formed a distinct lineage within the genus Paenibacillus that was
closely related to Paenibacillusyunnanensis JCM 30953T (98.6 %),
Paenibacillusvulneris CCUG 53270T (98.0 %) and Paenibacilluschinjuensis DSM
15045T (96.9 %). Cells were non-motile, endospore-forming and formed milky
colonies on NA and R2A agar media. Growth of strain SK-3146T occurred at
temperatures of 18-45 degrees C, at pH 6.0-9.5 and between 0.5-3.0 % NaCl (w/v).
The major menaquinone was MK-7, with lesser amounts of MK-6 present. The cell
wall peptidoglycan of strain SK-3146T contained meso-diaminopimelic acid. The
major fatty acids were anteiso-C15 : 0 and iso-C16 : 0. The major polar lipids
were diphosphatidylglycerol and phosphatidylethanolamine. The DNA G+C content was
53.8 mol% and the DNA-DNA hybridization relatedness values between strain SK
3146T and P.yunnanensis JCM 30953T and P.vulneris CCUG 53270T were 26.13+/-0.8 %
and 38.7+/-0.6 %, respectively. The phenotypic, phylogenetic and chemotaxonomic
results indicate that strain SK-3146T represents a novel species of the genus
Paenibacillus, for which the name Paenibacillus konkukensis sp. nov. is proposed.
The type strain is SK-3146T (=KACC 18876T=LMG 29568T).
PMID- 28699881
TI - Chemical composition and cytotoxicity of extracts of marjoram and rosemary and
their activity against Sporothrix brasiliensis.
AB - PURPOSE: Motivated by increasing reports of antifungal resistance in human and
animal sporotrichosis, this study evaluated the chemical composition,
cytotoxicity and anti-Sporothrix brasiliensis activity of extracts of marjoram
(Origanum majorana) and rosemary (Rosmarinus officinalis). METHODOLOGY: Ten
(INF10) and 60 min (INF60) infusions, a decoction and a hydroalcoholic extract
(HAE, 70 %) were prepared from both plants (10 % w/v). The extract composition
was analysed by liquid chromatography/mass spectrometry and the cytotoxicity was
evaluated using a colorimetric assay in canine and feline kidney cells. Using a
broth microdilution assay (CLSI M38-A2) adapted to the extracts, 30 Sporothrix
brasiliensis isolates from dogs, cats and humans, and one Sporothrix schenckii
were tested.Results/Key findings. The predominant phenolic compounds found in all
extracts were 4-hydroxybenzoic acid, caffeic acid and chlorogenic acid. Luteolin
was also one of the predominant compounds, but only in the HAE of marjoram.
Extracts of marjoram maintained cell viability in concentrations up to 2.5 mg ml
1 for the feline cell line and up to 10 mg ml-1 for the canine cell line, whereas
in rosemary, the cell viability for both kidney lines was maintained with
concentrations up to 5 mg ml-1. The activity of rosemary extracts was low or
absent. Among the marjoram extracts, HAE was highlighted and had fungistatic
activity against Sporothrix brasiliensis (MIC5040 mg ml-1), including in all
itraconazole-resistant isolates. S. schenckiisensu stricto was sensitive to
marjoram extracts (MIC/MFC <=5 mg ml-1), with the exception of INF10. CONCLUSION:
These findings support the potential usefulness of the HAE of marjoram in the
treatment of sporotrichosis.
PMID- 28699882
TI - Thalassotalea litorea sp. nov., isolated from seashore sand.
AB - A novel Gram-stain-negative, aerobic and rod-shaped marine bacterium, designated
strain HMF4135T, was isolated from a sand sample which was collected from the
seashore of the South Sea, Republic of Korea. It required NaCl for growth and
exhibited optimal growth at 30 degrees C, with 2 % (w/v) NaCl and at pH 7-8.
Cellular fatty acids were dominated by C16 : 0, summed feature 3 (C16 : 1omega7c
and/or C16 : 1omega6c), C16 : 1omega9c and C12 : 0 3-OH. The predominant
isoprenoid quinone was ubiquinone-8 (Q-8). Polar lipids consisted of
phosphatidylglycerol and phosphatidylethanolamine. The DNA G+C content was 41.9
mol%. Phylogeny based on 16S rRNA gene sequences showed that strain HMF4135T
formed a distinct species-level lineage within the genus Thalassotalea of the
class Gammaproteobacteria and was most closely related to Thalassotalea ponticola
GJSW-36T (96.4 % similarity). Based on the distinctive phenotypic characteristics
and phylogenetic analysis, it is concluded that strain HMF4135T represents a
novel species of the genus Thalassotalea, for which the name Thalassotalea
litorea sp. nov. is proposed. The type strain is HMF4135T (=KCTC 52154T=NBRC
112672T).
PMID- 28699883
TI - Familial melanoma-astrocytoma syndrome: synchronous diffuse astrocytoma and
pleomorphic xanthoastrocytoma in a patient with germline CDKN2A/B deletion and a
significant family history.
AB - Familial melanoma-astrocytoma syndrome is a tumor predisposition syndrome caused
by inactivating germline alteration of the CDKN2A tumor
suppressor gene on chromosome 9p21. While some families with germline
CDKN2A mutations are prone to development of just melanomas,
other families develop both melanomas, astrocytomas, and occasionally other
nervous-system neoplasms including peripheral nerve sheath tumors and
meningiomas. The histologic spectrum of the astrocytomas that arise as part of
this syndrome is not well described, nor are the additional genetic alterations
that drive these astrocytomas apart from the germline CDKN2A
inactivation. Herein, we report the case of a young man with synchronous
development of a pleomorphic xanthoastrocytoma, diffuse astrocytoma, and
paraspinal mass radiographically consistent with a peripheral nerve sheath tumor.
His paternal family history is significant for melanoma, glioblastoma, and oral
squamous cell carcinoma. Genomic profiling revealed that he harbors a
heterozygous deletion in the germline of chromosome 9p21.3 encompassing the
CDKN2A and CDKN2B tumor suppressor genes. Both
the pleomorphic xanthoastrocytoma and diffuse astrocytoma were found to have
homozygous deletion of CDKN2A/B due to somatic loss of the other
copy of chromosome 9p containing the remaining intact alleles. Additional somatic
alterations included BRAF p.V600E mutation in the pleomorphic
xanthoastrocytoma and PTPN11, ATRX, and
NF1 mutations in the diffuse astrocytoma. The presence of
germline CDKN2A/B inactivation together with the presence of
multiple anatomically, histologically, and genetically distinct astrocytic
neoplasms, both with accompanying somatic loss of heterozygosity for the
CDKN2A/B deletion, led to a diagnosis of familial melanoma
astrocytoma syndrome. This remarkable case illustrates the histologic and genetic
diversity that astrocytomas arising as part of this rare glioma predisposition
syndrome can demonstrate.?.
PMID- 28699884
TI - Survey among nephrologists in Germany: current practice and management of
pregnant women on dialysis?.
AB - BACKGROUND: To assess the experience and practice patterns of nephrologists in
Germany with regard to the care of pregnant women on dialysis. METHODS: The 26
item internet survey sent by email asked for demographic information, subjective
proficiency, maternal and fetal complications, treatment approaches and goals.
RESULTS: Of the 2,015 surveys sent out, 200 (10%) were available for evaluation.
38% of respondents never provided care, whereas 62% treated at least one pregnant
patient on dialysis. In 306 total reported cases of pregnant women on dialysis,
58% became pregnant while on maintenance dialysis, and 42% developed dialysis
dependent renal failure in the course of pregnancy. For women on peritoneal
dialysis (PD), only 22% of the nephrologists would continue PD until delivery,
while 78% would convert to hemodialysis either immediately or shortly before
delivery. 40% of the respondents reported complications in either mother or
child. 45% of the respondents routinely provided prenatal counseling, and 2/3 of
the nephrologists did not routinely perform fetal monitoring. While we found a
significant difference in self-reported proficiency between nephrologists having
and those not having treated pregnant women on dialysis, only 40% of all
physicians felt confident in treating pregnant women on dialysis. CONCLUSIONS:
Our survey demonstrates that the practice of nephrologists in treating pregnant
women on dialysis differs significantly. These findings highlight the need for
European guidelines to standardize the care of pregnant dialysis patients.?.
PMID- 28699885
TI - Does Helicobacter pylori infection play a role in iron deficiency anemia in
hemodialysis patients?
AB - BACKGROUND: Among the disorders that may affect patients with end-stage renal
disease (ESRD), anemia is the most responsive to treatment; any reversible cause
should be identified, and the most common reversible cause is iron deficiency. We
investigated the relationship between Helicobacter pylori
infection and iron deficiency anemia in a hemodialysis population. MATERIALS AND
METHODS: This cross-sectional study included 90 adult patients with ESRD on
maintenance hemodialysis. Iron deficiency anemia (IDA) was determined by
hemoglobin, serum iron, ferritin, and transferrin saturation (TSAT) values.
H. pylori diagnosis was done by detection of H.
pylori antigen in stool. RESULTS: It was found that H.
pylori stool antigen was positive in 50 patients (55.6%), while 40
patients were negative for H. pylori (44.4%). 71% of patients
had anemia (Hb < 10 g/dL), and 63% of patients had iron deficiency anemia (TSAT <
30%). No significant differences were found between H. pylori
positive and -negative groups in any of the variables analyzed: hemoglobin (8.96
+/- 1.8 vs.9.76 +/- 1.4 g/dL), serum iron (86 +/- 17.5 vs. 87 +/- 18.2 pg/dL),
ferritin (284.8 +/- 60.5 vs. 301.4 +/- 50.1 ng/dL), or TSAT index (26.79 +/-
18.42% vs. 29.83 +/- 18. 01% ug/dL). CONCLUSION: H. pylori
infection has a nonsignificant effect on iron deficiency anemia in hemodialysis
patients. We recommend that routine screening for H. pylori is
not needed among dialysis patients with iron deficiency anemia.?.
PMID- 28699886
TI - Interleukin-1 inhibition, chronic kidney disease-mineral and bone disorder, and
physical function?.
AB - OBJECTIVE: Epidemiologic studies have suggested a link between chronic systemic
inflammation and chronic kidney disease-mineral and bone disorder (CKD-MBD).
Additionally, declining renal function is associated with worsening physical and
cognitive function, which may potentially be explained by systemic inflammation,
CKD-MBD, or both. We hypothesized that inhibiting inflammation with an
interleukin-1 (IL-1) trap would improve markers of CKD-MBD as well as
physical/cognitive function in patients with moderate-to-severe CKD. METHODS: In
a two-site, double-blind trial, 39 patients with stage 3 - 4 CKD completed a
randomized trial receiving either the IL-1 trap rilonacept (160 mg/week) or
placebo for 12 weeks. The following CKD-MBD markers were assessed in serum before
and after the intervention: calcium, phosphorus, 25-hydroxyvitamin D, 1,25
dihydroxyvitamin D, 24,25-dihydroxyvitamin D, intact parathyroid hormone (iPTH),
and fibroblast growth factor 23 (FGF23). A battery of tests was also administered
in a subgroup (n = 23) to assess multiple domains of physical function
(endurance, locomotion, dexterity, balance, strength, and fatigue) and cognitive
function. RESULTS: Participants were 65 +/- 10 years of age, 23% female, and had
a mean estimated glomerular filtration rate of 38 +/- 13
mL/min/1.73m2. There were no changes in serum calcium, phosphorus, any
vitamin D metabolite, iPTH, or FGF23 levels (p >= 0.28) with IL-1 inhibition.
Similarly, rilonacept did not alter locomotion, dexterity, balance, strength,
fatigue, or cognitive function (p >= 0.13). However, endurance (400-m walk time)
tended to improve in the rilonacept (-31 s) vs. placebo group (-2 s; p = 0.07).
CONCLUSIONS: In conclusion, 12 weeks of IL-1 inhibition did not improve markers
of CKD-MBD or physical function.?.
PMID- 28699887
TI - Upward trend of dapsone-induced methemoglobinemia in renal transplant community?.
AB - Dapsone, a sulfone antibiotic, is used for prophylaxis of Pneumocystis
jirovecii pneumonia in patients with documented sulfa allergy. Acquired
methemoglobinemia caused by dapsone is not uncommon in patients with normal
glucose-6-phosphate dehydrogenase (G6PD) levels. Discrepancy between oxygen
saturation measured by pulse oximetry and arterial oxygen saturation
(SpO2) readings, a phenomenon known as "saturation gap," is noted with
cases of methemoglobinemia. Although its prevalence in renal transplant patients
is poorly described, there is evidence that its incidence is increasing. Here we
describe a case series of 4 patients who were switched from trimethoprim
sulfamethoxazole (TMP-SMX) to dapsone and subsequently developed
methemoglobinemia. Symptoms occur at varying methemoglobin levels and are more
severe in patients with pre-existing coronary disease or chronic lung disease.
Early recognition and cessation of dapsone is imperative, especially in renal
transplant.?.
PMID- 28699888
TI - Predicting augmented renal clearance using estimated glomerular filtration rate
in critically-ill children?.
AB - AIMS: Measured glomerular filtration rate (mGFR) is often used to identify
augmented renal clearance (ARC). However, in the clinical setting, estimated GFR
(eGFR) is obtained more quickly and inexpensively. We aimed to determine whether
eGFR can identify ARC by evaluating the correlation between the eGFR and
vancomycin trough level (VTL). MATERIALS AND METHODS: We retrospectively reviewed
the records of patients aged <= 18 years who underwent vancomycin therapeutic
drug monitoring at our tertiary hospital from July 2009 to June 2014. VTL, serum
creatinine concentration, eGFR, and clinical factors affecting VTL were analyzed.
RESULTS: Of 101 patients, 76 (75.25%) had a subtherapeutic VTL. Patient age (p =
0.006), the daily vancomycin dose (p = 0.041) and dosing interval (p = 0.006),
and eGFR (p < 0.001) affected the VTL. Multivariate analysis showed a significant
relationship between eGFR and VTL (adjusted R2, 0.812; p < 0.001). An
increased eGFR (odds ratio, 1.002; 95% confidence interval, 1.001 - 1.003; p =
0.001) was a risk factor for a subtherapeutic vancomycin level. The cutoff eGFR
value predicting a subtherapeutic vancomycin level was 110.51
mL/min/1.73m2 (area under the curve, 0.753). CONCLUSIONS: The eGFR
correlates with the VTL, and the eGFR cutoff value can predict a subtherapeutic
vancomycin level. eGFR is a reliable and efficient alternative to mGFR for
identifying ARC.?.
PMID- 28699889
TI - Evidence that Mediator is essential for Pol II transcription, but is not a
required component of the preinitiation complex in vivo.
AB - The Mediator complex has been described as a general transcription factor, but it
is unclear if it is essential for Pol II transcription and/or is a required
component of the preinitiation complex (PIC) in vivo. Here, we show that
depletion of individual subunits, even those essential for cell growth, causes a
general but only modest decrease in transcription. In contrast, simultaneous
depletion of all Mediator modules causes a drastic decrease in transcription.
Depletion of head or middle subunits, but not tail subunits, causes a downstream
shift in the Pol II occupancy profile, suggesting that Mediator at the core
promoter inhibits promoter escape. Interestingly, a functional PIC and Pol II
transcription can occur when Mediator is not detected at core promoters. These
results provide strong evidence that Mediator is essential for Pol II
transcription and stimulates PIC formation, but it is not a required component of
the PIC in vivo.
PMID- 28699890
TI - Changes of mitochondrial ultrastructure and function during ageing in mice and
Drosophila.
AB - Ageing is a progressive decline of intrinsic physiological functions. We examined
the impact of ageing on the ultrastructure and function of mitochondria in mouse
and fruit flies (Drosophila melanogaster) by electron cryo-tomography and
respirometry. We discovered distinct age-related changes in both model organisms.
Mitochondrial function and ultrastructure are maintained in mouse heart, whereas
subpopulations of mitochondria from mouse liver show age-related changes in
membrane morphology. Subpopulations of mitochondria from young and old mouse
kidney resemble those described for apoptosis. In aged flies, respiratory
activity is compromised and the production of peroxide radicals is increased. In
about 50% of mitochondria from old flies, the inner membrane organization breaks
down. This establishes a clear link between inner membrane architecture and
functional decline. Mitochondria were affected by ageing to very different
extents, depending on the organism and possibly on the degree to which tissues
within the same organism are protected against mitochondrial damage.
PMID- 28699919
TI - Towards sensitive, high-throughput, biomolecular assays based on fluorescence
lifetime.
AB - Time-resolved fluorescence detection for robust sensing of biomolecular
interactions is developed by implementing time-correlated single photon counting
in high-throughput conditions. Droplet microfluidics is used as a promising
platform for the very fast handling of low-volume samples. We illustrate the
potential of this very sensitive and cost-effective technology in the context of
an enzymatic activity assay based on fluorescently-labeled biomolecules.
Fluorescence lifetime detection by time-correlated single photon counting is
shown to enable reliable discrimination between positive and negative control
samples at a throughput as high as several hundred samples per second.
PMID- 28699891
TI - Lunatic fringe-mediated Notch signaling regulates adult hippocampal neural stem
cell maintenance.
AB - Hippocampal neural stem cells (NSCs) integrate inputs from multiple sources to
balance quiescence and activation. Notch signaling plays a key role during this
process. Here, we report that Lunatic fringe (Lfng), a key modifier of the Notch
receptor, is selectively expressed in NSCs. Further, Lfng in NSCs and Notch
ligands Delta1 and Jagged1, expressed by their progeny, together influence NSC
recruitment, cell cycle duration, and terminal fate. We propose a new model in
which Lfng-mediated Notch signaling enables direct communication between a NSC
and its descendants, so that progeny can send feedback signals to the 'mother'
cell to modify its cell cycle status. Lfng-mediated Notch signaling appears to be
a key factor governing NSC quiescence, division, and fate.
PMID- 28699920
TI - Systematic periodicity in waviness of vertically aligned carbon nanotubes
explained by helical buckling.
AB - A hypothesis is proposed in this work to account for the geometry of individual
vertically aligned carbon nanotubes (VACNTs) that not only justifies the
directionality of their growth, but also explains the origin of the waviness
frequently reported for these nanotube forests. Such waviness has fundamental
effects on the transport/conduction properties of VACNTs, either through or along
them, regarding phenomena such as mass, stress, heat and electricity. Despite the
general opinion about randomness of carbon nanotubes (CNTs) tortuosity, we
demonstrate here that rules of helical buckling of tubular strings is applicable
to VACNTs, based on which a regular 3D helical geometry is proposed for VACNTs,
with a 2D sine wave shape side-profile. In this framework, gradual increase of
the total free surface energy by growth of CNTs ensues their partial cohesion,
driven by van der Waals interactions, to reduce the excess surface energy. On the
other hand, their cohesion is accompanied by their deformation and loss of
straightness, which in turn, translates to buildup of an elastic strain energy in
the system. The balance of the two energies along with the spatial constraints on
each CNT at its contact points with neighboring CNTs, is manifested in its
helical buckling, that is systematically influenced by nanostructural
characteristics of VACNTs, such as their diameter, wall thickness and inter-CNT
spacing.
PMID- 28699921
TI - Enhanced piezoresponse of highly aligned electrospun poly(vinylidene fluoride)
nanofibers.
AB - Well-ordered nanostructure arrays with controlled densities can potentially
improve material properties; however, their fabrication typically involves the
use of complicated processing techniques. In this work, we demonstrate a uniaxial
alignment procedure for fabricating poly(vinylidene fluoride) (PVDF) electrospun
nanofibers (NFs) by introducing collectors with additional steps. The mechanism
of the observed NF alignment, which occurs due to the concentration of lateral
electric field lines around collector steps, has been elucidated via finite
difference time-domain simulations. The membranes composed of well-aligned PVDF
NFs are characterized by a higher content of the PVDF beta-phase, as compared to
those manufactured from randomly orientated fibers. The piezoelectric energy
harvester, which was fabricated by transferring well-aligned PVDF NFs onto
flexible substrates with Ag electrodes attached to both sides, exhibited a 2-fold
increase in the output voltage and a 3-fold increase in the output current as
compared to the corresponding values obtained for the device manufactured from
randomly oriented NFs. The enhanced piezoresponse observed for the aligned PVDF
NFs is due to their higher beta-phase content, denser structure, smaller
effective radius of curvature during bending, greater applied strain, and higher
fraction of contributing NFs.
PMID- 28699922
TI - A magnetic shift register with out-of-plane magnetized layers.
AB - Using out-of-plane magnetized layers, a lateral shift register made from discrete
elements is demonstrated. By carefully designing the in-plane shape of the
elements which make up the shift register, both the position of nucleation of new
domains and the coercivity of the element can be controlled. The dipole field
from a neighboring element, placed tens of nanometers away, creates a bias field
on the nucleation site, which can be used to create a NOT gate. By chaining these
NOT gates together, a shift register can be created where data bits consisting of
neighboring layers with aligned magnetization are propagated synchronously under
a symmetric applied magnetic field. The operation of a 16 element shift register
is shown, including field coupled data injection.
PMID- 28699923
TI - The Effects of Moderate- Versus High-Load Resistance Training on Muscle Growth,
Body Composition, and Performance in Collegiate Women.
AB - Cholewa, JM, Rossi, FE, MacDonald, C, Hewins, A, Gallo, S, Micenski, A, Norton,
L, and Campbell, BI. The effects of moderate- versus high-load resistance
training on muscle growth, body composition, and performance in collegiate women.
J Strength Cond Res 32(6): 1511-1524, 2018-Twenty young women (20.3 + 1.5 years,
164 + 6 cm, 68.7 + 13.8 kg) without prior structured resistance training
experience were recruited for this study. Body composition (BodPod),
compartmental water (Bioelectrical Impedance), 7-site skinfold, and arm and thigh
cross-sectional area (CSA) were assessed before and after 8-week training.
Performance testing consisted of vertical jump, 3-kg chest pass initial velocity,
squat 1RM, and overhead press 1RM. After 2 weeks of familiarization training,
subjects were matched for body composition and relative squat strength and
randomly assigned to either a high-load (HL: n = 10; 4 sets of 5-7 repetitions)
or moderate-load (ML: n = 10; 2 sets of 10-14 repetitions) group that completed 6
7 exercises per day performed to momentary muscular failure. Training was divided
into 2 lower and one upper body training sessions per week performed on
nonconsecutive days for 8 weeks. There were no statistically significant main
effects for group or group * time interactions for any variable assessed. Both HL
and ML resulted in similar significant increases in lean body mass (1.5 +/- 0.83
kg), lean dry mass (1.32 +/- 0.62 kg), thigh CSA (6.6 +/- 5.6 cm), vertical jump
(2.9 +/- 3.2 cm), chest pass velocity (0.334 +/- 1.67 m.s), back squat one
repetition maximum (1RM) (22.5 +/- 8.1 kg), and overhead press (3.0 +/- 0.8 kg).
High-load group and ML group also both resulted in significant decreases in
percent body fat (1.3 +/- 1.3%), total body water (0.73 +/- 0.70 L), and
intracellular water (0.43 +/- 0.38 L). The results of this study indicate that
both moderate-load and high-load training are effective at improving muscle
growth, body composition, strength and power in untrained young women.
PMID- 28699924
TI - Position-Specific Acceleration and Deceleration Profiles in Elite Youth and
Senior Soccer Players.
AB - Vigh-Larsen, JF, Dalgas, U, and Andersen, TB. Position-specific acceleration and
deceleration profiles in elite youth and senior soccer players. J Strength Cond
Res 32(4): 1114-1122, 2018-The purpose of the study was to characterize and
compare the position-specific activity profiles of young and senior elite soccer
players with special emphasis put on accelerations and decelerations. Eight
professional senior matches were tracked using the ZXY tracking system and
analyzed for the number of accelerations and decelerations and running distances
within different speed zones. Likewise, 4 U19 and 5 U17 matches were analyzed for
comparison between youth and senior players. In senior players, the total
distance (TD) was 10,776 +/- 107 m with 668 +/- 28 and 143 +/- 10 m being high
intensity running (HIR) and sprinting, respectively. Number of accelerations and
decelerations were 81 +/- 2 and 84 +/- 3, respectively, with central defenders
performing the lowest and wide players the highest number. Declines were found
between first and second halves for accelerations and decelerations (11 +/- 3%),
HIR (6 +/- 4%), and TD (5 +/- 1%), whereas sprinting distance did not differ. U19
players performed a higher number of accelerations, decelerations, and TD
compared with senior players. In conclusion, differences in the number and
distribution of accelerations and decelerations appeared between player
positions, which is of importance when monitoring training and match loads and
when prescribing specific training exercises. Furthermore, youth players
performed as much high-intensity activities as senior players, indicating that
this is not a discriminating physiological parameter between these players.
PMID- 28699925
TI - Quantifying Baseline Fixed Charge Density in Healthy Human Cartilage Endplate: A
Two-point Electrical Conductivity Method.
AB - STUDY DESIGN: Regional measurements of fixed charge densities (FCDs) of healthy
human cartilage endplate (CEP) using a two-point electrical conductivity
approach. OBJECTIVE: The aim of this study was to determine the FCDs at four
different regions (central, lateral, anterior, and posterior) of human CEP, and
correlate the FCDs with tissue biochemical composition. SUMMARY OF BACKGROUND
DATA: The CEP, a thin layer of hyaline cartilage on the cranial and caudal
surfaces of the intervertebral disc, plays an irreplaceable role in maintaining
the unique physiological mechano-electrochemical environment inside the disc.
FCD, arising from the carboxyl and sulfate groups of the glycosaminoglycans (GAG)
in the extracellular matrix of the disc, is a key regulator of the disc ionic and
osmotic environment through physicochemical and electrokinetic effects. Although
FCDs in the annulus fibrosus (AF) and nucleus pulposus (NP) have been reported,
quantitative baseline FCD in healthy human CEP has not been reported. METHODS:
CEP specimens were regionally isolated from human lumbar spines. FCD and ion
diffusivity were concurrently investigated using a two-point electrical
conductivity method. Biochemical assays were used to quantify regional GAG and
water content. RESULTS: FCD in healthy human CEP was region-dependent, with FCD
lowest in the lateral region (P = 0.044). Cross-region FCD was 30% to 60% smaller
than FCD in NP, but similar to the AF and articular cartilage (AC). CEP FCD
(average: 0.12 +/- 0.03 mEq/g wet tissue) was correlated with GAG content
(average: 31.24 +/- 5.06 MUg/mg wet tissue) (P = 0.005). In addition, the cross
region ion diffusivity in healthy CEP (2.97 +/- 1.00 * 10 cm/s) was much smaller
than the AF and NP. CONCLUSION: Healthy human CEP acts as a biomechanical
interface, distributing loads between the bony vertebral body and soft disc
tissues and as a gateway impeding rapid solute diffusion through the disc. LEVEL
OF EVIDENCE: N/A.
PMID- 28699926
TI - PREVALENCE OF FOVEOLAR LUCENCY WITH DIFFERENT GAS TAMPONADES IN SURGICALLY CLOSED
MACULAR HOLES ASSESSED BY SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY.
AB - PURPOSE: To evaluate the prevalence of foveolar lucency (FL) in surgically closed
macular holes by spectral domain optical coherence tomography. METHODS: One
hundred forty-two eyes of 132 patients underwent pars plana vitrectomy, internal
limiting membrane peeling, and gas tamponade in a 60-month time frame. Anatomical
success and FL rates assessed by spectral domain optical coherence tomography,
mean preoperative, and postoperative best-measured visual acuity and surgical
details were retrospectively analyzed. RESULTS: Spectral domain optical coherence
tomography confirmed closed holes with FL in 33.7% (34/101) of eyes at 1 month,
7.3% (9/123) at 3 months, 4.6% (6/129) at 6 months, and 3% (4/133) at 12 months.
Prevalence of FL in closed holes at Month 1 was lower in C3F8-treated eyes (9.5%,
2/21) compared with C2F6 (40.9%, 18/44, P = 0.03) and SF6-treated eyes (38.9%,
14/36, P = 0.05). No differences were observed at Month 3. No differences in best
measured visual acuity change were observed between closed holes with or without
FL at Month 1 (-0.14 +/- 0.19 vs. -0.11 +/- 0.23, P = 0.48) or any of the other
time points. CONCLUSION: Temporary FL is a highly prevalent feature in
successfully closed macular holes. Eyes treated with C3F8 gas had lower rates of
FL at Month 1 than C2F6 and SF6-treated eyes. The presence of FL in closed holes
does not seem to have any effect on the visual outcomes.
PMID- 28699927
TI - SHORT-TERM OUTCOMES AFTER INTRAVITREAL INJECTIONS OF CONBERCEPT VERSUS
RANIBIZUMAB FOR THE TREATMENT OF RETINOPATHY OF PREMATURITY.
AB - PURPOSE: Intravitreal injection of conbercept (IVC) is the latest applied
treatment that could be used in retinopathy of prematurity (ROP) patients. The
structural outcomes and recurrence of ROP among patients treated with IVC or
intravitreal injection of ranibizumab (IVR) were compared. METHODS: A consecutive
case series of ROP treated with IVC or IVR were retrospectively studied. The
primary outcome was treatment success defined as regression of plus disease. The
secondary outcomes were recurrence of plus, times of injection, and the final
regression of disease. RESULTS: A total of 48 eyes (24 patients) with ROP were
included. Twenty eyes (10 patients) received IVC, and 28 eyes (14 patients)
received IVR. For the IVC group, 18 eyes had Zone II 3+ ROP and 2 eyes had
aggressive posterior ROP. Among the 28 eyes treated with IVR, 6 eyes had Zone I
2/3+ ROP, 6 eyes had aggressive posterior ROP, and 16 eyes had Zone II 3+ ROP.
For the IVC group, the mean gestational age, birth weight, postmenstrual age at
initial treatment, and follow-up period for the infants were 29.49 +/- 1.37
weeks, 1,369.0 +/- 161.9 g, 38.47 +/- 2.72 weeks, and 52.6 +/- 21.4 weeks,
respectively. And for the infants who received IVR, these were 28.35 +/- 1.62
weeks, 1,171.4 +/- 279.9 g, 38.53 +/- 3.54 weeks, and 42.9 +/- 9.8 weeks,
respectively. For the IVC group, 17 (85%) of 20 eyes received the injection only
once, and the regression of plus disease occurred 4.3 +/- 2.08 weeks later. Three
eyes (15%) did not healed with one injection received a second IVC, and the
regression of plus disease occurred within 3 weeks. For the IVR group, 15/28
(53.6%) eyes received a second IVR. Among them, 10 recurrent eyes and 5 eyes did
not recover with one injection. No retinal detachment was observed in both group
infants. CONCLUSION: Both conbercept and ranibizumab are effective choice for the
treatment of ROP. Conbercept is a novel effective treatment strategy for ROP
providing a new treatment option for ophthalmologists.
PMID- 28699928
TI - ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY VERSUS PHOTODYNAMIC THERAPY IN
THE TREATMENT OF CHOROIDAL NEOVASCULARIZATION SECONDARY TO CENTRAL SEROUS
CHORIORETINOPATHY.
AB - PURPOSE: To evaluate the efficacy of photodynamic therapy (PDT) compared with
intravitreal vascular endothelial growth factor (VEGF) inhibitors alone or
combined with PDT in the treatment of choroidal neovascularization (CNV)
secondary to chronic central serous chorioretinopathy (CSCR). METHODS:
Retrospective study of a consecutive series of 34 white patients (34 eyes) with
angiographic evidence of choroidal neovascularization secondary to chronic
central serous chorioretinopathy, divided into two groups followed for at least
12 months: 16 were treated with full fluence PDT (PDT group) and 18 with vascular
endothelial growth factor inhibitors (intravitreal [IVT] group). RESULTS: In the
PDT group, mean best-corrected visual acuity (BCVA) was 20/40 (0.30 +/- 0.69
logMAR) at baseline and did not change after 12 months (20/40; 0.30 +/- 0.49
logMAR [P = 0.49]). In the IVT group mean, best-corrected visual acuity was 20/40
(0.30 +/- 0.69 logMAR) at baseline and also did not change at the 12-month follow
up (20/32; 0.20 +/- 0.49 logMAR [P = 0.20]). There was no statistically
significant difference between the two groups in terms of best-corrected visual
acuity. A statistical significance difference was found in central macular
thickness between the two groups with a better reduction of the thickening in the
PDT group (P = 0.05); moreover, indocyanine green angiography analysis revealed
that 50% of the polypoidal lesions were closed after PDT and 25% of the
polypoidal lesions disappeared after anti-vascular endothelial growth factor
therapy at 12-month follow-up. CONCLUSION: PDT and IVT inhibitors alone or
combined show similar clinical effects in chronic central serous
chorioretinopathy eyes with choroidal neovascularization.
PMID- 28699929
TI - ARCUATE NERVE FIBER LAYER CHANGES AFTER INTERNAL LIMITING MEMBRANE PEELING IN
IDIOPATHIC EPIRETINAL MEMBRANE.
AB - PURPOSE: To analyze the relationship between swelling of the arcuate nerve fiber
layer (SANFL) and long-term decrease of retinal nerve fiber layer thickness after
internal limiting membrane peeling for idiopathic epiretinal membrane, and to
investigate if SANFL is related to a mechanical surgical damage. METHODS:
Prospective, interventional consecutive case series of 46 eyes that underwent
combined epiretinal membrane/internal limiting membrane peeling for idiopathic
epiretinal membrane. Infrared, blue autofluorescence, color fundus imaging and
measurement of retinal nerve fiber layer thickness in six peripapillary sectors
by spectral-domain optical coherence tomography were performed preoperatively and
at 2 weeks, 1, 3, 6, and 12 months after surgery. The presence of SANFL was
checked postoperatively on infrared and blue autofluorescence fundus imaging, and
the extent of each SANFL was measured on infrared fundus images. RESULTS: Areas
of SANFL were identified in 39 eyes (84.8%) at 2-week follow-up. Retinal nerve
fiber layer thickness significantly decreased in the temporal sectors at 1, 6,
and 12 months (P < 0.0001). The linear extent of SANFL was significantly
correlated with the percentage of reduction in retinal nerve fiber layer
thickness in the temporal (R = 0.45; P < 0.0001) and infero-temporal (R = 0.23; P
= 0.0008) sectors at 12 months of follow-up. Correspondence between sites of
surgical grasping and the points of origin of SANFL was demonstrated on blue
autofluorescence fundus images superimposed on intraoperative surgical frames.
CONCLUSION: Early postoperative SANFL is correlated with late focal retinal nerve
fiber layer thinning in the temporal sectors. Intraoperative surgical grasping
seems to be a leading factor for the onset of SANFL.
PMID- 28699930
TI - Two-Stage Surgery to Manage Massive Suprachoroidal Hemorrhage.
PMID- 28699931
TI - Drugs for Helicobacter pylori infection.
PMID- 28699932
TI - Broadalumab (Siliq)--another IL-17A antagonist for psoriasis.
PMID- 28699933
TI - Telotristat ethyl (Xermelo) for carcinoid syndrome diarrhea.
PMID- 28699934
TI - In brief: Avelumab (Bavencio) for metastatic merkel cell carcinoma.
PMID- 28699935
TI - Use of Simulation to Assess Incoming Interns' Recognition of Opportunities to
Choose Wisely.
AB - BACKGROUND: Despite increasing healthcare costs, training on cost-consciousness
is lacking in graduate medical education (GME). Medical centers must consider how
best to incorporate value-based training into their GME curricula. OBJECTIVE: To
incorporate low-value principles into an existing GME simulation exercise and
assess incoming interns' recognition of low-value care. METHODS: Choosing
WiselyTM lists were reviewed to identify 4 low-value hazards to be embedded into
a simulated hospital room in addition to the 8 patient safety hazards used
previously. Interns were given 10 minutes to independently review a mock chart
and list all hazards they identified in the simulation. Interns completed a short
survey on their prior training in medical school and a follow-up survey one month
into internship. ?? tests used to compare identification of low-value vs safety
hazards and to associate performance with prior training. RESULTS: The mean
percentage of hazards correctly identified was 50.4% (standard deviation [SD]
11.8%). Interns identified significantly fewer low-value hazards (mean 19.2%, SD
18.6%) than safety hazards (mean 66.0%, SD 16.0%; ?? < .001). For example, while
96% of interns identified the hand hygiene hazard, only 6% identified the
unnecessary blood transfusion and none identified the unnecessary stress ulcer
prophylaxis. Interns who self-reported as confident in their ability to identify
hazards were not any more likely to correctly identify hazards than those who
were not confident. CONCLUSIONS: The "Room of Horrors" simulation revealed poor
awareness of low-value care among interns. The simulation highlights a promising
model for the prioritization and inclusion of value-based experiential training
in GME.
PMID- 28699936
TI - Clinician Attitudes Regarding ICD Deactivation in DNR/DNI Patients.
AB - BACKGROUND: Implantable cardioverter-defibrillators (ICDs) offer lifesaving
therapies but can become burdensome at the end of life. Many ICD patients choose
to implement a do-not-resuscitate/do-not-intubate (DNR/DNI) order. When
hospitalized, patients are seen by a range of clinicians whose beliefs about ICD
management in DNR/DNI patients may vary. OBJECTIVE: To assess clinician opinions
on managing ICDs in DNR/DNI patients and stratify it by specialty and training
level. METHODS: An online survey was sent to attending physicians, fellows,
advanced practice providers (physician assistants and nurse practitioners), and
residents in general internal medicine, cardiology, electrophysiology, and
geriatrics at an academic medical center. Residents were compared to attending
physicians, and attending physicians were additionally stratified by specialty.
RESULTS: The response rate was 32%, yielding 161 complete responses. Among
residents (n = 73), 49.3% were comfortable with discussing ICD deactivation and
16.4% asked about it routinely. By contrast, among attending physicians (n = 66),
78.8% were comfortable with discussing deactivation and 34.8% routinely asked.
Fewer general internists (19.2% of inpatient internists, 10.5% of outpatient
internists) routinely asked about ICD deactivation as compared with 83.3% of
geriatricians and 73.3% of cardiologists/electrophysiologists. Twenty-one percent
of all respondents felt a DNR/DNI order equated to requesting ICD deactivation;
Heart Rhythm Society (HRS) guidelines favor a more nuanced approach. CONCLUSIONS:
Residents are less comfortable discussing ICD deactivation than attending
physicians and do so less frequently. General internists discuss deactivation
less routinely than cardiologists and geriatricians. Many providers hold opinions
about ICD deactivation that differ from HRS guidelines. Additional didactic
education could help close these gaps in clinician practice.
PMID- 28699937
TI - Techniques and Behaviors Associated with Exemplary Inpatient General Medicine
Teaching: An Exploratory Qualitative Study.
AB - BACKGROUND: Clinician educators face numerous obstacles to their joint mission of
facilitating high-quality learning while also delivering patient-centered care.
Such challenges necessitate increased attention to the work of exemplary
clinician educators, their respective teaching approaches, and the experiences of
their learners. OBJECTIVE: To describe techniques and behaviors utilized by
clinician educators to facilitate excellent teaching during inpatient general
medicine rounds. DESIGN: An exploratory qualitative study of inpatient teaching
conducted from 2014 to 2015. SETTING: Inpatient general medicine wards in 11 US
hospitals, including university-affiliated hospitals and Veterans Affairs medical
centers. PARTICIPANTS: Participants included 12 exemplary clinician educators, 57
of their current learners, and 26 of their former learners. MEASUREMENTS: In
depth, semi-structured interviews of exemplary clinician educators, focus group
discussions with their current and former learners, and direct observations of
clinical teaching during inpatient rounds. RESULTS: Interview data, focus group
data, and observational field notes were coded and categorized into broad,
overlapping themes. Each theme elucidated a series of actions, behaviors, and
approaches that exemplary clinician educators consistently demonstrated during
inpatient rounds: (1) they fostered positive relationships with all team members
by building rapport, which in turn created a safe learning environment; (2) they
facilitated patient-centered teaching points, modeled excellent clinical exam and
communication techniques, and treated patients as partners in their care; and (3)
they engaged in coaching and collaboration through facilitation of discussion,
effective questioning strategies, and differentiation of learning among team
members with varied experience levels. CONCLUSIONS: This study identified
consistent techniques and behaviors of excellent teaching during inpatient
general medicine rounds.
PMID- 28699938
TI - A Simple Algorithm for Predicting Bacteremia Using Food Consumption and Shaking
Chills: A Prospective Observational Study.
AB - BACKGROUND: Predicting the presence of true bacteremia based on clinical
examination is unreliable. OBJECTIVE: We aimed to construct a simple algorithm
for predicting true bacteremia by using food consumption and shaking chills.
DESIGN: A prospective multicenter observational study. SETTING: Three hospital
centers in a large Japanese city. PARTICIPANTS: In total, 1,943 hospitalized
patients aged 14 to 96 years who underwent blood culture acquisitions between
April 2013 and August 2014 were enrolled. Patients with anorexia-inducing
conditions were excluded. INTERVENTIONS: We assessed the patients' oral food
intake based on the meal immediately prior to the blood culture with definition
as "normal food consumption" when >80% of a meal was consumed and "poor food
consumption" when <80% was consumed. We also concurrently evaluated for a history
of shaking chills. MEASUREMENTS: We calculated the statistical characteristics of
food consumption and shaking chills for the presence of true bacteremia, and
subsequently built the algorithm by using recursive partitioning analysis.
RESULTS: Among 1,943 patients, 223 cases were true bacteremia. Among patients
with normal food consumption, without shaking chills, the incidence of true
bacteremia was 2.4% (13/552). Among patients with poor food consumption and
shaking chills, the incidence of true bacteremia was 47.7% (51/107). The presence
of poor food consumption had a sensitivity of 93.7% (95% confidence interval
[CI], 89.4%-97.9%) for true bacteremia, and the absence of poor food consumption
(ie, normal food consumption) had a negative likelihood ratio (LR) of 0.18 (95%
CI, 0.17-0.19) for excluding true bacteremia, respectively. Conversely, the
presence of the shaking chills had a specificity of 95.1% (95% CI, 90.7%-99.4%)
and a positive LR of 4.78 (95% CI, 4.56-5.00) for true bacteremia. CONCLUSION: A
2-item screening checklist for food consumption and shaking chills had excellent
statistical properties as a brief screening instrument for predicting true
bacteremia.
PMID- 28699939
TI - Implementing ACOVE Quality Indicators as an Intervention Checklist to Improve
Care for Hospitalized Older Adults.
AB - BACKGROUND: Medicare patients account for approximately 50% of hospital days.
Hospitalization in older adults often results in poor outcomes. OBJECTIVE: To
test the feasibility and impact of using Assessing Care of Vulnerable Elders
(ACOVE) quality indicators (QIs) as a therapeutic intervention to improve care of
hospitalized older adults. DESIGN: >Post-test only prospective intervention with
a nonequivalent retrospective control group. SETTING: Large tertiary hospital in
the greater New York Metropolitan area. PATIENTS: Hospitalized patients, 75 years
and over, admitted to medical units. INTERVENTION: A checklist, comprised of four
ACOVE QIs, administered during daily interdisciplinary rounds: venous thrombosis
prophylaxis (VTE) (QI 1), indwelling bladder catheters (QI 2), mobilization (QI
3), and delirium evaluation (QI 4). MEASUREMENTS: Variables were extracted from
electronic medical records with QI compliance as primary outcome, and length of
stay (LOS), discharge disposition, and readmissions as secondary outcomes.
Generalized linear mixed models for binary clustered data were used to estimate
compliance rates for each group (intervention group or control group) in the
postintervention period, along with their corresponding 95% confidence intervals.
RESULTS: Of the 2,396 patients, 530 were on an intervention unit. In those
patients not already compliant with VTE, compliance rate was 57% in intervention
vs 39% in control (?? < .0056). For indwelling catheters, mobilization, and
delirium evaluation, overall compliance was significantly higher in the
intervention group 72.2% vs 54.4% (?? = .1061), 62.9% vs 48.2% (?? < .0001), and
27.9% vs 21.7% (?? = .0027), respectively. CONCLUSION: The study demonstrates the
feasibility and effectiveness of integrating ACOVE QIs to improve the quality of
care in hospitalized older adults.
PMID- 28699940
TI - Association of Stress Biomarkers With 30-Day Unplanned Readmission and Death.
AB - BACKGROUND: The theory that posthospitalization stress might increase the risk of
postdischarge complications has never been investigated. OBJECTIVE: To assess
whether serum levels of stress biomarkers at discharge are associated with
readmission and death after an acute-care hospitalization. DESIGN: We
prospectively included 346 patients aged >=50 years admitted to the department of
general internal medicine at a large community hospital between April 8, 2013 and
September 23, 2013. We measured the serum levels of several biomarkers at
discharge: midregional pro-adrenomedullin, copeptin, cortisol, and prolactin. All
patients were followed for up to 90 days after discharge (none was lost to follow
up). The main outcome was first unplanned readmission or death within 30 days
after hospital discharge. We assessed the additional value of biomarkers to 2
validated readmission prediction scores: the LACE index (Length of stay,
Admission Acuity, Charlson Comorbidity Index, and number of Emergency department
visits within preceding 6 months) and the HOSPITAL score (Hemoglobin level at
discharge, discharge from Oncology service, Sodium level at discharge, any
Procedure performed during index hospitalization, Index admission Type, number of
Admissions within preceding 12 months, and Length of stay). RESULTS: Forty
patients (11.6%) had a 30-day unplanned readmission or death. High serum copeptin
and cortisol levels were associated with an increase in the odds of unplanned
readmission or death (odds ratios [95% confidence interval] 2.69 [1.29-5.64] and
3.43 [1.36, 8.65], respectively). We found no significant association with
midregional pro-adrenomedullin or prolactin. Furthermore, these stress biomarkers
increased the performance of two readmission prediction scores (LACE index and
HOSPITAL score). CONCLUSION: High serum levels of copeptin and cortisol at
discharge were independently associated with 30-day unplanned readmission or
death, supporting a possible negative effect of hospitalization stress during the
postdischarge period. Stress biomarkers improved the performance of prediction
models and therefore could help better identify high-risk patients.
PMID- 28699941
TI - Hospital-Based Clinicians' Use of Technology for Patient Care-Related
Communication: A National Survey.
AB - OBJECTIVE: To characterize current use of communication technologies, including
standard text messaging and secure mobile messaging applications, for patient
care-related (PCR) communication. METHODS: We used a Society of Hospital Medicine
database to conduct a national cross-sectional survey of hospital-based
clinicians. RESULTS: We analyzed data from 620 survey respondents (adjusted
response rate, 11.0%). Pagers were provided by hospitals to 495 (79.8%) of these
clinicians, and 304 (49%) of the 620 reported they received PCR messages most
commonly by pager. Use of standard text messaging for PCR communication was
common, with 300 (52.9%) of 567 clinicians reporting receipt of standard text
messages once or more per day. Overall, 21.5% (122/567) of respondents received
standard text messages that included individually identifiable information, 41.3%
(234/567) received messages that included some identifiable information (eg,
patient initials), and 21.0% (119/567) received messages for urgent clinical
issues at least once per day. About one-fourth of respondents (26.6%, 146/549)
reported their organization had implemented a secure messaging application that
some clinicians were using, whereas few (7.3%, 40/549) reported their
organization had implemented an application that most clinicians were using.
DISCUSSION: Pagers remain the technology most commonly used by hospital-based
clinicians, but a majority also use standard text messaging for PCR
communication, and relatively few hospitals have fully implemented secure mobile
messaging applications. CONCLUSION: The wide range of technologies used suggests
an evolution of methods to support communication among healthcare professionals.
PMID- 28699942
TI - Hospital-Level Factors Associated with Pediatric Emergency Department Return
Visits.
AB - BACKGROUND: Return visits (RVs) and RVs with admission (RVAs) are commonly used
emergency department quality measures. Visit- and patient-level factors,
including several social determinants of health, have been associated with RV
rates, but hospital-specific factors have not been studied. OBJECTIVE: To
identify what hospital-level factors correspond with high RV and RVA rates.
SETTING: Multicenter mixed-methods study of hospital characteristics associated
with RV and RVA rates. DATA SOURCE: Pediatric Health Information System with
survey of emergency department directors. MEASUREMENTS: Adjusted return rates
were calculated with generalized linear mixed-effects models. Hospitals were
categorized by adjusted RV and RVA rates for analysis. RESULTS: Twenty-four
hospitals accounted for 1,456,377 patient visits with an overall adjusted RV rate
of 3.7% and RVA rate of 0.7%. Hospitals with the highest RV rates served
populations that were more likely to have government insurance and lower median
household incomes and less likely to carry commercial insurance. Hospitals in the
highest RV rate outlier group had lower pediatric emergency medicine specialist
staffing, calculated as full-time equivalents per 10,000 patient visits: median
(interquartile range) of 1.9 (1.5-2.1) versus 2.9 (2.2-3.6). There were no
differences in hospital population characteristics or staffing by RVA groups.
CONCLUSION: RV rates were associated with population social determinants of
health and inversely related to staffing. Hospital-level variation may indicate
population-level economic factors outside the control of the hospital and
unrelated to quality of care.
PMID- 28699943
TI - Dosing Accuracy of Direct Oral Anticoagulants in an Academic Medical Center.
AB - BACKGROUND/OBJECTIVE: Direct-acting oral anticoagulants (DOACs) are increasingly
used to prevent or treat thromboembolism. We conducted a study to compare how
well initial DOAC prescribing for adult inpatients adhered to dosing
recommendations approved by the US Food and Drug Administration (FDA). DESIGN:
Retrospective analysis. SETTING: Single academic medical center, July 1, 2014 to
June 30, 2015. PATIENTS: 508 adult inpatients. MEASUREMENTS: DOAC prescriptions
were evaluated to determine whether they met FDA-recommended dosing and
administration according to patient age, weight, sex, race, kidney function,
diagnoses, and concomitant medications. RESULTS: DOACs were prescribed in 635
admissions (247 apixaban, 97 dabigatran, 291 rivaroxaban). The indication was
atrial fibrillation/flutter in 465 admissions (8% with bioprostheses or valve
repair), chronic deep vein thrombosis (DVT) in 67, acute DVT in 32, chronic
pulmonary embolism in 23, acute pulmonary embolism in 19, DVT prevention after
hip or knee surgery in 19, and non-FDA-approved indications in 10. Sixteen
percent of orders for venous thromboembolic disease were for patients with active
malignancy. Dosages not concordant with recommendations were prescribed for
apixaban in 18% of admissions, for rivaroxaban in 14%, and for dabigatran in 7%
(?? = 0.04). Lower than recommended dosing was more common than higher than
recommended dosing (?? < 0.05). Half the deviations were continuations of
outpatient dosing. Atrial fibrillation/flutter and post-hip or -knee surgery
dosing deviations were more common than venous thromboembolic disease deviations
(?? < 0.001) but were not related to prescriber specialty. CONCLUSIONS: DOAC
prescribing recommendation deviations that can affect clinical efficacy were
identified. Education and point-of-care decision support tools for improving
dosing are needed, as are outcome data for patients who receive DOACs at lower
than recommended dosing or for off-label indications.
PMID- 28699944
TI - Improving the Readability of Pediatric Hospital Medicine Discharge Instructions.
AB - BACKGROUND: Readable discharge instructions may help caregivers understand and
implement care plans following hospitalization. Many caregivers of hospitalized
children, however, have limited literacy. We aimed to increase the percentage of
discharge instructions written at 7th grade level or lower for hospital medicine
patients from 13% to 80% in 6 months. METHODS: Quality improvement efforts
targeted a 42-bed unit at the community satellite of our large, urban academic
hospital. A multidisciplinary team of physicians, nurses, and parents focused on
key drivers: family engagement in discharge process, standardization of discharge
instructions, staff engagement in discharge preparedness, and audit and feedback
of data. Improvement cycles included 1) education and implementation of a general
discharge instruction template in the electronic health record (EHR); 2) visible
reminders and tips for writing readable discharge instructions; 3) implementation
of disease-specific discharge instruction templates in the EHR; and 4)
individualized feedback to staff on readability and content of their written
discharge instructions. Instructions were individually scored for readability
using an online platform. An annotated control chart assessed the impact of
interventions over time. RESULTS: Through sequential interventions over 6 months,
the percentage of discharge instructions written at 7th grade or lower
readability level increased from 13% to 98% and has been sustained for 4 months.
The reliable use of the EHR templates was associated with our largest
improvements. CONCLUSION: Use of standardized discharge instruction templates and
rapid feedback to staff improved the readability of instructions. Next steps
include adaptation and spread to other patient populations.
PMID- 28699945
TI - Contextual Influences of Trainee Characteristics and Daily Workload on Trainee
Learning Preferences.
AB - We previously defined teaching domains necessary for successful inpatient
medicine attending rounds from the trainees' perspective in Role Modeling,
Learning Environment, Teaching Process and Team Management. We sought to
understand whether trainee characteristics and daily fluctuations in workload
influence the prioritization of these domains. We conducted a prospective
observational study in general medicine inpatient wards at a university, Veterans
Affairs, and a county hospital affiliated with one academic institution over the
course of 6 months. All student and resident trainees on internal medicine
inpatient wards were eligible to participate. We designed a daily assessment tool
on which trainees were asked to identify the teaching domain most important to
them, along with information on sex, training level, call-cycle day, patient
census, and number of team members absent during rounds. We examined associations
between training level and workload factors with the prioritized teaching domain
using Pearson's chi-square analysis, adjusted for clustering effects. We
collected 1,378 daily assessment cards evaluating 53 (91%) attending physicians.
Students valued Teaching Process (?? < 0.001), while senior residents sought Team
Management (?? < 0.001). On most days, Teaching Process was prioritized (?? =
0.005). On post-call days and days with a high patient census, Team Management
was prioritized (?? < 0.001). Attending physicians may consider tailoring rounds
in response to work-related pressures. Days with a high workload are better
suited for demonstrating efficient and effective patient care skills.
PMID- 28699946
TI - Using Standardized Patients to Assess Hospitalist Communication Skills.
AB - Standardized patients (SPs) have been used to assess communication skills in
undergraduate medical education, but no published studies describe the use of SPs
in assessing practicing physicians on their communication skills. In this study,
done with 23 hospitalists at a large urban academic hospital, 3 SP scenarios,
daily rounding, discharge, and interacting with a difficult patient, were
created. After each encounter, each hospitalist reviewed their videotape and
received feedback from their SP based on a checklist that had 3 core domains:
Listen, Courtesy and Respect, and Explain. These domains correlated with the 3
questions in the Hospital Consumer Assessment of Healthcare Providers and Systems
survey that relate to doctors. Hospitalists performed significantly better in the
Listen domain, with a mean percent adequate score of 90.2% (95% confidence
interval [CI], 72.2%-100%; ?? < 0.05), and significantly worse in the Explain
domain, with a mean percent adequate score of 65.0% (95% CI, 49.2%-83.6%; ?? <
0.05). Checklist items in the Explain domain that were most commonly not
performed adequately were summarizing information at the end of the encounter,
teach back, encouraging additional questions, managing team and self-up, setting
expectations about length of stay, and timing of tests. After the SP encounters,
hospitalists felt more confident in their communication skills. SPs can be used
to assess and give feedback to hospitalists and increase confidence in several
aspects of communication.
PMID- 28699947
TI - Fecal Occult Blood Testing in Hospitalized Patients with Upper Gastrointestinal
Bleeding.
AB - A 47-year-old man with a history of alcohol abuse, cirrhosis, and grade II
esophageal varices is admitted for treatment of alcohol withdrawal. He reports
having some dark-colored stools a week prior to admission, but his stools since
then have been normal in color. A repeat hemoglobin is stable, but a fecal occult
blood test is positive. What should be done next?
PMID- 28699948
TI - AcademyHealth's Delivery System Science Fellowship: Training Embedded Researchers
to Design, Implement, and Evaluate New Models of Care.
AB - AcademyHealth's Delivery System Science Fellowship (DSSF) provides a paid
postdoctoral pragmatic learning experience to build capacity within learning
healthcare systems to conduct research in applied settings. The fellowship
provides hands-on training and professional leadership opportunities for
researchers. Since its inception in 2012, the program has grown rapidly, with 16
health systems participating in the DSSF to date. In addition to specific
projects conducted within health systems (and numerous publications associated
with those initiatives), the DSSF has made several broader contributions to the
field, including defining delivery system science, identifying a set of training
objectives for researchers working in delivery systems, and developing a national
collaborative network of care delivery organizations, operational leaders, and
trainees. The DSSF is one promising approach to support higher-value care by
promoting continuous learning and improvement in health systems.
PMID- 28699949
TI - The Plot Thickens.
AB - OBJECTIVE: DESIGN: SETTING: PATIENTS: MEASUREMENTS: RESULTS: CONCLUSIONS:
PMID- 28699950
TI - The Hospitalized Patient with Interstitial Lung Disease: A Hospitalist Primer.
AB - Interstitial lung disease (ILD) is a diverse group of disorders typically with
insidious onset. Diagnosis and management largely occur in the outpatient
setting; however, ILD can present acutely necessitating hospitalization.
Effective inpatient management requires the clinician to establish an accurate
diagnosis and understand the natural history and treatment responsiveness of each
ILD subtype. We propose a general framework for approaching the evaluation of
hospitalized patients with ILD, and provide focused guidance on key inpatient
diagnostic and management decisions.
PMID- 28699963
TI - Nitrogen and phosphorus flux from the production of Nile tilapia through the
application of environmental indicators.
AB - We aimed in this study utilize environmental indicators as a quantitative method
to evaluate and discuss the nitrogen (TN) and phosphorus (TP) flux by a
production stage grow-out (termination) of Nile tilapia (Oreochromis niloticus)
in fishpond. The TN and TP load, the mass balance, the input of TN and TP via
feed and the converted nutrients in fish biomass are the environmental indicators
applied in this study. During the production cycle (128 days), the system
exported 15,931 g TN and 4,189 g TP that were related to the amount of feed
supplied (r Pearson = 0.8825 and r = 0.8523, respectively), corroborated by the
feed conversion ratio (1.61:1). The indicators showed that 26% TN and 45% TP were
reversed into fish biomass, 62% TN and 40% TP were retained in the fishpond, and
12% TN and 15% TP were exported via effluent. The largest contribution of
nutrients generated by the system and exported via effluent was observed in phase
III and IV. This result is supported by the feed conversion ratio 2.14 and 2.21:1
obtained at this phase, a fact explained by the amount of feed offered and the
fish metabolism. Application of environmental indicators showed to be an
efficient tool to quantify flux of TN and TP produced during the grow-out period
of Nile tilapia and therefore, guide management practices more sustainable.
Concerning the environmental sustainability of the activity the implementation of
best management practices such as the better control of the feed amount offered
would lead to a smaller loss of TN and TP to the water. Furthermore, the use of
better quality feeds would allow greater nutrient assimilation efficiency.
PMID- 28699964
TI - Antifungal susceptibility profile of diferent yeasts isolates from wild animals,
cow's milk with subclinical mastitis and hospital environment.
AB - Yeast infections have acquired great importance due to increasing frequency in
immunocompromised patients or patients undergoing invasive diagnostic and
therapeutic techniques, and also because of its high morbidity and mortality. At
the same time, it has been seen an increase in the emergence of new pathogenic
species difficult to diagnose and treat. The aim of this study was to determine
the in vitro susceptibility of 89 yeasts from different sources against the
antifungals amphotericin B, voriconazole, fluconazole and flucytosine, using the
VITEK(r) 2 Compact system. The antifungal susceptibility was performed
automatically by the Vitek(r) 2 Compact system. The origin of the yeasts was:
Group 1 - microbiota of wild animals (W) (26/89), 2 - cow's milk with subclinical
mastitis (M) (27/89) and 3 - hospital enviorment (H) (36/89). Of the 89 yeasts
submitted to the Vitek(r) 2 test, 25 (20.9%) were resistant to fluconazole, 11
(12.36%) to amphotericin B, 3 (3.37%) to voriconazole, and no sample was
resistant to flucytosine. Regarding the minimum inhibitory concentration (MIC),
fluconazole showed an MIC between 1 and 64 mg/mL for the three groups,
voriconazole had an MIC between 0.12 and 8 mg/mL, amphotericin B had an MIC
between 0.25 and 4 mg/mL for group H and group W respectively, between 0.25 and
16 mg/mL for group M and flucytosine had an MIC equal to 1MUg/mL for all groups.
The yeasts isolated from the H group showed the highest resistance to fluconazole
12/89 (13.49%), followed by group W (7.87%) and group M (5.62%). The more
resistant group to voriconazole was followed by the M and H groups, the W group
showed no resistance to this antifungal. Group H was the least resistant (2.25%)
to amphotericin.
PMID- 28699965
TI - Bacterial degradation of dissolved organic matter released by Planktothrix
agardhii (Cyanobacteria).
AB - Although Planktothrix agardhii often produces toxic blooms in eutrophic water
bodies around the world, little is known about the fate of the organic matter
released by these abundant Cyanobacteria. Thus, this study focused in estimating
the bacterial consumption of the DOC and DON (dissolved organic carbon and
dissolved organic nitrogen, respectively) produced by axenic P. agardhii cultures
and identifying some of the bacterial OTUs (operational taxonomic units) involved
in the process. Both P. agardhii and bacterial inocula were sampled from the
eutrophic Barra Bonita Reservoir (SP, Brazil). Two distinct carbon degradation
phases were observed: during the first three days, higher degradation
coefficients were calculated, which were followed by a slower degradation phase.
The maximum value observed for particulate bacterial carbon (POC) was 11.9 mg L
1, which consisted of 62.5% of the total available DOC, and its mineralization
coefficient was 0.477 day-1 (t1/2 = 1.45 days). A similar pattern of degradation
was observed for DON, although the coefficients were slightly different. Changes
in the OTUs patterns were observed during the different steps of the degradation.
The main OTUs were related to the classes Alphaproteobacteria (8 OTUs),
Betaproteobacteria (2 OTUs) and Gammaproteobacteria (3 OTUs). The genus
Acinetobacter was the only identified organism that occurred during the whole
process. Bacterial richness was higher at the slower degradation phase, which
could be related to the small amounts of DOM (dissolved organic matter)
available, particularly carbon. The kinetics of the bacterial degradation of P.
agardhii-originated DOM suggests minimal loss of DOM from the Barra Bonita
reservoir.
PMID- 28699966
TI - Proteomic profile of Piper tuberculatum (Piperaceae).
AB - Piper tuberculatum (Piperaceae) is a species that accumulates especially amides
as secondary metabolites and several biological activities was previously
reported. In this article, we report a proteomic study of P. tuberculatum.
Bidimensional electrophoresis (2D SDS-PAGE) and mass spectrometry (ESI-Q-TOF)
were used in this study. Over a hundred spots and various peptides were
identified in this species and the putative functions of these peptides related
to defense mechanism as biotic and abiotic stress were assigned. The information
presented extend the range of molecular information of P. tuberculatum.
PMID- 28699967
TI - Accumulation of copper by the aquatic macrophyte Salvinia biloba Raddi
(Salviniaceae).
AB - Aquatic macrophytes have properties and mechanisms which are useful for the
removal of substances in solution, commonly used in phytoremediation processes in
aquatic environments. This study evaluated the performance of copper (Cu)
accumulation by Salvinia biloba Raddi (Salviniaceae) in different metal
concentrations (1, 3 and 5 ug mL-1), as well as the control treatment, measured
at intervals of 0, 7 and 14 days under laboratory conditions, with control as to
pH and luminosity. After the experiment, the S. biloba biomass was washed, kiln
dried, crushed and subjected to the process of digestion, and subsequently the
accumulated copper content was determined by atomic absorption spectroscopy. The
results showed that S. biloba is apt at accumulating copper, varying
significantly between different treatments and days of exposure to the
contaminant, as well as its interaction (treatment * days). The highest
accumulation values were observed in treatment with 5 ug mL-1, which at 14 days,
with 11,861 ug g-1 of copper. We observed symptoms of toxicity and mortality in
plants, probably indicating the effect of copper on the species when at high
levels. Salvinia biloba is an efficient species in the removal of copper in
solution, its recommendation as a remediating agent in aquatic ecosystems being
possible.
PMID- 28699968
TI - Phytochemistry, antioxidant potential and antifungal of Byrsonima crassifolia on
soil phytopathogen control.
AB - The use of chemical defensives to control fungal diseases has by consequence to
impact negatively over the environment and human health, this way, the use of
plant extracts with antifungal properties along with proper cultural management
makes viable an alternative plant production control, specially for familiar and
organic cultures. The objective of this study was to perform phytochemical and
antioxidant analysis of Byrsonima crassifolia (canjiqueira) barks and evaluate
its antifungal potential over Fusarium solani and Sclerotinia sclerotiorum
mycelial growth. The ethanol extract from plants collected in Pantanal, Mato
Grosso do Sul, Brazil was submitted to phytochemical prospection, total phenol
and flavonoids quantification and antioxidant activiy determination (DPPH). To
evaluate antifungal activity concentrations of 800, 1200, 1600, 2000 and 2400 ug
100 mL-1 of ethanol extract were used. Which concentration was separately
incorporated in agar (PDA) and shed in Petri dishes, followed by the fungi
mycelial disc where the colonies diameter was measured daily. Negatives control
with agar without extract and agar with an ethanol solution were used. The B.
crassifolia ethanol extract presented inhibitory activity over the fungi studied
where concentrations of 800 and 1600 ug 100 mL-1, inhibited 38% of the mycelial
growth of F. solani; to S. sclerotiorum the best concentration was 2400 ug 100
mL1, reducing 37.5%. The antifungal bark extract potential of this specie is
attributed to phenolic compounds and to triterpenes derivatives.
PMID- 28699969
TI - The effect of size and density on nut removal in Syagrus loefgrenii Glassman
(Arecaceae) in the Brazilian Cerrado.
AB - In this study I tested the effect of Syagrus loefgrenii nut size and number on
the intensity of removal by rodents across seasons. Trials were performed in
which piles of either small or large endocarps (1, 3, 6, 12, and 25) were
subjected to removal by rodents in the Cerrado (Brazilian savanna). Despite of
variations in the intensity of removal, always this process decrease conform
endocarp number. Also, mean proportion of endocarp removal was unrelated to year
period, initial number, and size of endocarps. Hence, endocarp removal was
consistently negative density-dependent. As, in principle, the observed patterns
of nut removal point out similar survival chances for both nut sizes, the
pervasive negative density-dependent response emerges as a strategy in S.
loefgrenii to swamp rodents all year round irrespective of seed size.
PMID- 28699970
TI - Reduction of doxorubicin-induced genotoxicity by Handroanthus impetiginosus in
mouse bone marrow revealed by micronucleus assay.
AB - Handroanthus impetiginosus has long been used in traditional medicine and various
studies have determined the presence of bioactive chemical compounds and
potential phytotherapeutics. In this study, the genotoxicity of the lyophilized
tincture of H. impetiginosus bark (THI) was evaluated in mouse bone marrow using
micronucleus assays. The interaction between THI and genotoxic effects induced by
the chemotherapeutic agent, doxorubicin (DXR), was also analyzed. Experimental
groups were evaluated 24 to 48 h after treatment with N-nitroso-N-ethylurea (NEU;
50 mg/kg), DXR (5 mg/kg), sodium chloride (NaCl; 150 mM), and THI (0.5-2 g/kg).
Antigenotoxic assays were carried out using THI (0.5 g/kg) in combination with
NEU or DXR. Analysis of the micronucleated polychromatic erythrocytes (MNPCEs)
indicated no significant differences between treatment doses of THI (0.5-2 g/kg)
and NaCl. Polychromatic erythrocyte (PCE) to normochromatic erythrocyte (NCE)
ratios did not indicate any statistical differences between DXR and THI or NaCl,
but there were differences between THI and NaCl. A significant reduction in
MNPCEs and PCE/NCE ratios was observed when THI was administered in combination
with DXR. This study suggested the absence of THI genotoxicity that was dose-,
time-, and gender-independent and the presence of moderate systemic toxicity that
was dose-independent, but time- and gender-dependent. The combination of THI and
DXR also suggested antigenotoxic effects, indicating that THI reduced genotoxic
effects induced by chemotherapeutic agents.
PMID- 28699971
TI - The Concept of Clinical Economics and its Relation with Effectiveness.
PMID- 28699972
TI - Long-term Results of a Cardiology Postgraduate Program.
PMID- 28699973
TI - Healthy School, Happy School: Design and Protocol for a Randomized Clinical Trial
Designed to Prevent Weight Gain in Children.
AB - Background: : Schools have become a key figure for the promotion of health and
obesity interventions, bringing the development of critical awareness to the
construction and promotion of a healthy diet, physical activity, and the
monitoring of the nutritional status in childhood and adolescence. Objectives: :
To describe a study protocol to evaluate the effectiveness of an intervention
designed to improve knowledge of food choices in the school environment. Methods:
: This is a cluster-randomized, parallel, two-arm study conducted in public
elementary and middle schools in Brazil. Participants will be children and
adolescents between the ages of 5 and 15 years, from both genders. The
interventions will be focusing on changes in lifestyle, physical activities and
nutritional education. Intervention activities will occur monthly in the school's
multimedia room or sports court. The control group arm will receive usual
recommendations by the school. The primary outcome variable will be
anthropometric measures, such as body mass index percentiles and levels of
physical activity by the International Physical Activity Questionnaire. Results:
: We expect that after the study children will increase the ingestion of fresh
food, reduce excessive consumption of sugary and processed foods, and reduce the
hours of sedentary activities. Conclusion: : The purpose of starting the dietary
intervention at this stage of life is to develop a knowledge that will enable for
healthy choices, providing opportunities for a better future for this population.
Fundamento: : As escolas tornaram-se essenciais para a promocao de saude e de
intervencoes para obesidade, propiciando o desenvolvimento de consciencia critica
para a construcao e promocao de dieta saudavel, atividade fisica e monitoramento
do status nutricional na infancia e adolescencia. Objetivos: : Descrever um
protocolo de estudo para avaliar a eficiencia de uma intervencao projetada para
aprimorar o conhecimento sobre escolhas alimentares no ambiente escolar. Metodos:
: Estudo clinico randomizado em cluster, paralelo, de dois bracos, conduzido em
escolas publicas de ensino fundamental e medio no Brasil. Os participantes serao
criancas e adolescentes entre 5 e 15 anos de idade, dos dois sexos. As
intervencoes se concentrarao em mudancas de estilo de vida, atividade fisica e
educacao nutricional. As atividades de intervencao ocorrerao mensalmente na sala
de multimidia ou quadra de esportes das escolas. O grupo controle recebera as
recomendacoes usuais atraves da escola. O desfecho primario sera a mudanca nas
medidas antropometricas, como indice de massa corporal e os niveis de atividade
fisica conforme o Questionario Internacional de Atividade Fisica. Resultados: :
Esperamos que, apos o estudo, as criancas aumentem o consumo de alimentos
frescos, reduzam o consumo excessivo de alimentos acucarados e processados, e
reduzam as horas gastas em atividades sedentarias. Conclusao: : O proposito de
iniciar a intervencao dietetica nessa fase da vida e desenvolver o conhecimento
que permitira escolhas saudaveis, propiciando oportunidades para um melhor futuro
para essa populacao.
PMID- 28699974
TI - Cardiovascular Risk Stratification and Statin Eligibility Based on the Brazilian
vs. North American Guidelines on Blood Cholesterol Management.
AB - Background: : The best way to select individuals for lipid-lowering treatment in
the population is controversial. Objective: : In healthy individuals in primary
prevention: to assess the relationship between cardiovascular risk categorized
according to the V Brazilian Guideline on Dyslipidemia and the risk calculated by
the pooled cohort equations (PCE); to compare the proportion of individuals
eligible for statins, according to different criteria. Methods: : In individuals
aged 40-75 years consecutively submitted to routine health assessment at one
single center, four criteria of eligibility for statin were defined: BR-1, BR-2
(LDL-c above or at least 30 mg/dL above the goal recommended by the Brazilian
Guideline, respectively), USA-1 and USA-2 (10-year risk estimated by the PCE >=
5.0% or >= 7.5%, respectively). Results: : The final sample consisted of 13,947
individuals (48 +/- 6 years, 71% men). Most individuals at intermediate or high
risk based on the V Brazilian Guideline had a low risk calculated by the PCE, and
more than 70% of those who were considered at high risk had this categorization
because of the presence of aggravating factors. Among women, 24%, 17%, 4% and 2%
were eligible for statin use according to the BR-1, BR-2, USA-1 and USA-2
criteria, respectively (p < 0.01). The respective figures for men were 75%, 58%,
31% and 17% (p < 0.01). Eighty-five percent of women and 60% of men who were
eligible for statin based on the BR-1 criterion would not be candidates for
statin based on the USA-1 criterion. Conclusions: : As compared to the North
American Guideline, the V Brazilian Guideline considers a substantially higher
proportion of the population as eligible for statin use in primary prevention.
This results from discrepancies between the risk stratified by the Brazilian
Guideline and that calculated by the PCE, particularly because of the risk
reclassification based on aggravating factors. Fundamento: : Existe controversia
sobre a melhor forma de selecionar individuos para tratamento hipolipemiante na
populacao. Objetivos: : Em individuos saudaveis em prevencao primaria: avaliar a
relacao entre o risco cardiovascular segundo a V Diretriz Brasileira de
Dislipidemias e o risco calculado pelas pooled cohort equations (PCE); comparar a
proporcao de individuos elegiveis para estatinas, de acordo com diferentes
criterios. Metodos: : Em individuos de 40 a 75 anos submetidos consecutivamente a
avaliacao rotineira de saude em um unico centro, quatro criterios de
elegibilidade para estatina foram definidos: BR-1, BR-2 (LDL-c acima ou pelo
menos 30 mg/dL acima da meta preconizada pela diretriz brasileira,
respectivamente), EUA-1 e EUA-2 (risco estimado pelas PCE em 10 anos >= 5,0% ou
>= 7,5%, respectivamente). Resultados: : Foram estudados 13.947 individuos (48 +/
6 anos, 71% homens). A maioria dos individuos de risco intermediario ou alto
pela V Diretriz apresentou risco calculado pelas PCE baixo e mais de 70% daqueles
considerados de alto risco o foram devido a presenca de fator agravante. Foram
elegiveis para estatina 24%, 17%, 4% e 2% das mulheres pelos criterios BR-1, BR
2, EUA-1 e EUA-2, respectivamente (p < 0,01). Os respectivos valores para os
homens foram 75%, 58%, 31% e 17% (p < 0,01). Oitenta e cinco por cento das
mulheres e 60% dos homens elegiveis para estatina pelo criterio BR-1 nao seriam
candidatos pelo criterio EUA-1. Conclusoes: : Comparada a diretriz norte
americana, a V Diretriz Brasileira considera uma proporcao substancialmente maior
da populacao como elegivel para estatina em prevencao primaria. Isso se relaciona
com discrepancias entre o risco estratificado pela diretriz brasileira e o
calculado pelas PCE, particularmente devido a reclassificacao de risco baseada em
fatores agravantes.
PMID- 28699975
TI - The Expected Cardiovascular Benefit of Plasma Cholesterol Lowering with or
Without LDL-C Targets in Healthy Individuals at Higher Cardiovascular Risk.
AB - Background:: There is controversy whether management of blood cholesterol should
be based or not on LDL-cholesterol (LDL-c) target concentrations. Objectives:: To
compare the estimated impact of different lipid-lowering strategies, based or not
on LDL-c targets, on the risk of major cardiovascular events in a population with
higher cardiovascular risk. Methods:: We included consecutive individuals
undergoing a routine health screening in a single center who had a 10-year risk
for atherosclerotic cardiovascular disease (ASCVD) >= 7.5% (pooled cohort
equations, ACC/AHA, 2013). For each individual, we simulated two strategies based
on LDL-c target (<= 100 mg/dL [Starget-100] or <= 70 mg/dL [Starget-70]) and two
strategies based on percent LDL-c reduction (30% [S30%] or 50% [S50%]). Results::
In 1,897 subjects (57 +/- 7 years, 96% men, 10-year ASCVD risk 13.7 +/- 7.1%),
LDL-c would be lowered from 141 +/- 33 mg/dL to 99 +/- 23 mg/dL in S30%, 71 +/-
16 mg/dL in S50%, 98 +/- 9 mg/dL in Starget-100, and 70 +/- 2 mg/dL in Starget
70. Ten-year ASCVD risk would be reduced to 8.8 +/- 4.8% in S50% and 8.9 +/- 5.2
in Starget-70. The number of major cardiovascular events prevented in 10 years
per 1,000 individuals would be 32 in S30%, 31 in Starget-100, 49 in S50%, and 48
in Starget-70. Compared with Starget-70, S50% would prevent more events in the
lower LDL-c tertile and fewer events in the higher LDL-c tertile. Conclusions::
The more aggressive lipid-lowering approaches simulated in this study, based on
LDL-c target or percent reduction, may potentially prevent approximately 50% more
hard cardiovascular events in the population compared with the less intensive
treatments. Baseline LDL-c determines which strategy (based or not on LDL-c
target) is more appropriate at the individual level. Fundamentos:: Ha
controversias sobre se o controle do colesterol plasmatico deve ou nao se basear
em metas de concentracao de colesterol LDL (LDL-c). Objetivos:: Comparar o
impacto estimado de diferentes estrategias hipolipemiantes, baseadas ou nao em
metas de LDL-c, sobre o risco de eventos cardiovasculares maiores em uma
populacao de risco cardiovascular mais elevado. Metodos:: Foram incluidos
individuos consecutivamente submetidos a uma avaliacao rotineira de saude em um
unico centro e que apresentavam um risco em 10 anos de doenca cardiovascular
aterosclerotica (DCVAS) >= 7,5% ("pooled cohort equations", ACC/AHA, 2013). Para
cada individuo, foram simuladas duas estrategias baseadas em meta de LDL-c (<=
100 mg/dL [Emeta-100] ou <= 70 mg/dL [Emeta-70]) e duas estrategias baseadas em
reducao percentual do LDL-c (30% [E30%] ou 50% [E50%]). Resultados:: Em 1.897
individuos (57 +/- 7 anos, 96% homens, risco em 10 anos de DCVAS 13,7 +/- 7,1%),
o LDL-c seria reduzido de 141 +/- 33 mg/dL para 99 +/- 23 mg/dL na E30%, 71 +/-
16 mg/dL na E50%, 98 +/- 9 mg/dL na Emeta-100 e 70 +/- 2 mg/dL na Emeta-70. O
risco em 10 anos de DCVAS seria reduzido para 8,8 +/- 4,8% na E50% e para 8,9 +/-
5,2 na Emeta-70. O numero de eventos cardiovasculares maiores prevenidos em 10
anos por 1.000 individuos seria de 32 na E30%, 31 na Emeta-100, 49 na E50% e 48
na Emeta-70. Em comparacao com a Emeta-70, a E50% evitaria mais eventos no tercil
inferior de LDL-c e menos eventos no tercil superior de LDL-c. Conclusoes:: As
abordagens hipolipemiantes mais agressivas simuladas neste estudo, com base em
meta de LDL-c ou reducao percentual, podem potencialmente prevenir cerca de 50%
mais eventos cardiovasculares graves na populacao em comparacao com os
tratamentos menos intensivos. Os niveis basais de LDL-c determinam qual
estrategia (baseada ou nao em meta de LDL-c) e mais apropriada para cada
individuo.
PMID- 28699976
TI - Discordant Lipid Pattern and Carotid Atherosclerotic Plaque. Importance of
Remnant Cholesterol.
AB - Background:: Subjects with levels of non-HDL-C 30 mg/dL above those of LDL-C
(lipid discordance) or with high remnant cholesterol levels could have a greater
residual cardiovascular risk. Objectives:: To determine the prevalence of lipid
discordance in a primary prevention population and analyze the clinical variables
associated with it; To investigate the association between lipid discordance and
remnant cholesterol with the presence of carotid plaque. Methods:: Primary
prevention patients without diabetes or lipid-lowering therapy were included.
Regardless of the LDL-C level, we define "lipid discordance" if the non-HDL-C
value exceeded 30 mg/dL that of LDL-C. Remnant cholesterol was calculated as
total cholesterol minus HDL-C minus LDL-C when triglycerides were < 4.0 mmol/L.
Ultrasound was used to assess carotid plaque occurrence. Multiple regression
logistic models were performed. Results:: The study included 772 patients (mean
age 52 +/- 11 years, 66% women). The prevalence of lipid discordance was 34%.
Male sex and body mass index were independently associated with discordant lipid
pattern. The prevalence of carotid plaque was higher in subjects with lipid
discordance (40.2% vs. 29.2, p = 0.002). The multivariate analysis showed that
the discordant lipid pattern was associated with the greater probability of
carotid plaque (OR 1.58, 95% CI 1.08-2.34, p = 0.02). Similarly, a significant
association between calculated remnant cholesterol and carotid plaque was found.
Conclusion:: Lipid discordance and presence of a higher level of calculated
remnant cholesterol are associated with subclinical atherosclerosis. Our findings
could be used to improve the residual cardiovascular risk evaluation.
Fundamento:: Individuos com niveis de nao HDL-C excedendo em 30 mg/dl aqueles de
LDL-C (discordancia lipidica) ou com altos niveis de colesterol remanescente
poderiam ter maior risco cardiovascular residual. Objetivos:: determinar a
prevalencia de discordancia lipidica em uma populacao de prevencao primaria e
analisar as variaveis clinicas com ela associadas; investigar a associacao de
discordancia lipidica e colesterol remanescente calculado com a presenca de placa
carotidea. Metodos:: Pacientes de prevencao primaria sem diabetes ou sem terapia
hipolipemiante foram incluidos. Independentemente do nivel de LDL-C, definiu-se
"discordancia lipidica" como um valor de nao HDL-C excedendo em 30 mg/dl aquele
de LDL-C. Calculou-se o colesterol remanescente como colesterol total menos HDL-C
menos LDL-C na presenca de triglicerideos < 4,0 mmol/l. Usou-se ultrassom para
avaliar a presenca de placa carotidea. Modelos de regressao logistica multipla
foram construidos. Resultados:: Este estudo incluiu 772 pacientes (idade media,
52 +/- 11 anos; 66% mulheres). A prevalencia de discordancia lipidica foi de 34%.
Sexo masculino e indice de massa corporal mostraram associacao independente com
padrao lipidico discordante. A prevalencia de placa carotidea foi maior em
individuos com discordancia lipidica (40,2% vs. 29,2; p = 0,002). A analise
multivariada mostrou associacao do padrao lipidico discordante com maior
probabilidade de placa carotidea (OR: 1,58; IC95%: 1,08-2,34; p = 0,02). Da mesma
forma, identificou-se uma significativa associacao entre colesterol remanescente
calculado e placa carotidea. Conclusao:: Discordancia lipidica e presenca de
nivel mais alto de colesterol remanescente calculado acham-se associados com
aterosclerose subclinica. Nossos achados podem ser usados para aprimorar a
avaliacao de risco cardiovascular residual.
PMID- 28699977
TI - Pacemaker Implants in Children and Adolescents with Chagas Disease in Brazil: 18
Year Incidence.
AB - Background:: Chagas disease continues to be a serious public health problem, and
accounts for 25-30% of the indications for cardiac stimulation in Brazil.
Objective:: To assess clinical and epidemiological characteristics of patients
with Chagas disease, younger than 18 years, who had undergone pacemaker
implantation in Brazil between 1994 and 2011, and its temporal trend. Methods::
This was a cross-sectional analysis of data from the Brazilian Pacemaker Registry
database. The following variables were analyzed: year when pacemaker was
implanted, location, age, sex, ethnic group, functional class and the main
electrocardiographic findings at baseline. Results:: In a total of 183,123
implants performed between 1994 and 2011, 214 implants of cardiac stimulation
device in Chagas disease patients aged younger than 18 years were identified.
Mean age at implantation was 5.6 +/- 6.2 years. Second- and third-degree
atrioventricular blocks corresponded to 71% of indications for pacemaker
implantation. Fifty-six percent of the procedures were performed in the southeast
region. Regarding the total number of pacemaker implants per year, there was a
remarkable increase in the implants for all causes. However, time series analysis
of the implants in Chagas disease patients younger than 18 years revealed a
significant reduction in the annual number of implants. Conclusion:: There has
been an important reduction in the number of pacemaker implantations among
children and adolescents with Chagas disease, suggesting a reduction in the
vertical transmission of the parasite. Fundamento:: A doenca de Chagas mantem-se
como serio problema de saude publica e tem sido responsavel por aproximadamente
25% a 30% das indicacoes de estimulacao cardiaca no Brasil. Objetivo:: Estudar as
caracteristicas clinicas e epidemiologicas dos pacientes menores de 18 anos
portadores de doenca de Chagas submetidos a implante de marca-passo no territorio
brasileiro entre 1994 e 2011, e sua tendencia temporal. Metodos:: Trata-se de um
estudo retrospectivo que utilizou informacoes coletadas pelo Registro Brasileiro
de Marca-passo. As variaveis analisadas foram: ano do implante, localidade,
idade, sexo, grupo etnico dos pacientes; classificacao funcional e os principais
achados eletrocardiograficos de base. Resultados:: Em um total de 183 123
implantes realizados entre 1994 e 2011, foram identificados 214 implantes de
dispositivos de estimulacao cardiaca em portadores de doenca de Chagas com idade
inferior a 18 anos. A media de idade no momento do implante foi de 5,6 +/- 6,2
anos. Bloqueios atrioventriculares de 2o e 3o graus foram responsaveis por 71%
das indicacoes. Dos procedimentos, 55,6% foram realizados na regiao sudeste. Em
relacao ao total de implantes de marca-passo por ano, observamos um aumento
importante e significante de implante por todas as causas. Entretanto, quando
avaliamos a serie temporal de implantes em pacientes com doenca de Chagas menores
que 18 anos, observamos uma reducao expressiva e significativa no numero anual de
implantes. Conclusao:: Observa-se uma reducao importante do numero de implantes
de marca-passo em criancas e adolescente chagasicos, o que sugere uma reducao da
transmissao vertical do parasita.
PMID- 28699978
TI - Cirrhotic Cardiomyopathy: A New Clinical Phenotype.
PMID- 28699979
TI - Case 4/2017 - Double-Chambered Right Ventricle with Dextrocardia and Hypoxemia
Due to Atrial Shunt in a 4-Year-Old Girl.
PMID- 28699980
TI - Myocardial Bridge and Angiotomography of the Coronary Arteries: Perfusion under
Pharmacological Stress.
PMID- 28699981
TI - Exuberant Vasospastic Angina Simulating Severe Three-Vessel Disease.
PMID- 28699982
TI - Erratum.
AB - [This corrects the article doi: 10.5935/abc.20120202] [This corrects the article
doi: 10.5935/abc.20170041].
PMID- 28699983
TI - Two themes in thyroid cancer: artful diagnosis and shortened lives.
PMID- 28699984
TI - Gestational diabetes mellitus and type 2 diabetes: same disease in a different
moment of life? Maybe not.
PMID- 28699985
TI - Glycated albumin: a potential biomarker in diabetes.
AB - Diabetes mellitus (DM) is a chronic and metabolic disease that presents a high
global incidence. Glycated hemoglobin (A1C) is the reference test for long-term
glucose monitoring, and it exhibits an association with diabetic chronic
complications. However, A1C is not recommended in clinical situations which may
interfere with the metabolism of hemoglobin, such as in hemolytic, secondary or
iron deficiency anemia, hemoglobinopathies, pregnancy, and uremia. The glycated
albumin (GA) is a test that reflects short-term glycemia and is not influenced by
situations that falsely alter A1C levels. GA is the higher glycated portion of
fructosamine. It is measured by a standardized enzymatic methodology, easy and
fast to perform. These laboratory characteristics have ensured the highlight of
GA in studies from the last decade, as a marker of monitoring and screening for
DM, as well as a predictor of long-term outcomes of the disease. The aim of this
review was to discuss the physiological and biochemistry characteristics of the
GA, as well as its clinical utility in DM.
PMID- 28699986
TI - Diagnosis and management of primary aldosteronism.
AB - Primary aldosteronism (PA) is the most common form of secondary hypertension
(HTN), with an estimated prevalence of 4% of hypertensive patients in primary
care and around 10% of referred patients. Patients with PA have higher
cardiovascular morbidity and mortality than age- and sex-matched patients with
essential HTN and the same degree of blood pressure elevation. PA is
characterized by an autonomous aldosterone production causing sodium retention,
plasma renin supression, HTN, cardiovascular damage, and increased potassium
excretion, leading to variable degrees of hypokalemia. Aldosterone-producing
adenomas (APAs) account for around 40% and idiopathic hyperaldosteronism for
around 60% of PA cases. The aldosterone-to-renin ratio is the most sensitive
screening test for PA. There are several confirmatory tests and the current
literature does not identify a "gold standard" confirmatory test for PA. In our
institution, we recommend starting case confirmation with the furosemide test.
After case confirmation, all patients with PA should undergo adrenal CT as the
initial study in subtype testing to exclude adrenocortical carcinoma. Bilateral
adrenal vein sampling (AVS) is the gold standard method to define the PA subtype,
but it is not indicated in all cases. An experienced radiologist must perform
AVS. Unilateral laparoscopic adrenalectomy is the preferential treatment for
patients with APAs, and bilateral hyperplasia should be treated with
mineralocorticoid antagonist (spironolactone or eplerenone). Cardiovascular
morbidity caused by aldosterone excess can be decreased by either unilateral
adrenalectomy or mineralocorticoid antagonist. In this review, we address the
most relevant issues regarding PA screening, case confirmation, subtype
classification, and treatment.
PMID- 28699987
TI - Relation between fetal anthropometric parameters and cord blood adiponectin and
high-sensitivity C-reactive protein in gestational diabetes mellitus.
AB - Objectives: The objectives were to evaluate the relation between fetal
anthropometric parameters and cord blood concentration of adiponectin and high
sensitivity C-reactive protein (hs-CRP). Subjects and methods: A total of 104
pregnant women (52 with gestational diabetes mellitus [GDM], 52 with normal
glucose tolerance (NGT) participated. Venous cord blood samples were obtained at
delivery, centrifuged and the plasma was stored at -20 degrees C. The samples
were assessed for adiponectin and hs-CRP using the ELISA method. Statistical
analysis was done using SPSS software. Results: The adiponectin concentration was
higher in the GDM group than in the NGT group (11.05 +/- 4.1 ug/mL in GDM vs.
5.34 +/- 2.63 ug/mL in NGT, p < 0.001). GDM was also higher in neonates delivered
at later gestational ages (p < 0.001, Pearson correlation = 0.59). There was a
positive correlation between cord blood adiponectin and birth weight in the GDM
group (p < 0.001, Pearson correlation = 0.619) but not in the NGT group. There
was no significant correlation between adiponectin and infant length or head
circumference. There was also no significant difference in cord blood hs-CRP
concentration between groups. No relation was found between hs-CRP and newborn
anthropometric parameters. Conclusion: In the GDM group, adiponectin
concentration was considerably higher and had a positive correlation with the
ponderal index and birth weight which was not found in the NGT group.
PMID- 28699988
TI - Type 2 diabetes-associated genetic variants of FTO, LEPR, PPARg, and TCF7L2 in
gestational diabetes in a Brazilian population.
AB - Objective: Gestational diabetes mellitus (GDM) is a metabolic disorder that
shares pathophysiologic features with type 2 diabetes mellitus. The aim of this
study was to investigate the association of the polymorphisms fat mass and
obesity-associated (FTO) rs1421085, leptin receptor (LEPR) rs1137100, rs1137101,
peroxisome proliferator-activated receptor gamma (PPARg) rs1801282, and
transcription factor 7-like 2 (TCF7L2) rs7901695 with GDM. Subjects and methods:
252 unrelated Euro-Brazilian pregnant women were classified into two groups
according to the 2015 criteria of the American and Brazilian Diabetes
Association: healthy pregnant women (n = 125) and pregnant women with GDM (n =
127), matched by age. The polymorphisms were genotyped using fluorescent probes
(TaqMan(r)). Results: All groups were in Hardy-Weinberg equilibrium. The genotype
and allele frequencies of the studied polymorphisms did not show significant
differences between the groups (P > 0.05). In the healthy and GDM groups, the C
allele frequencies (95% CI) of the FTO rs1421085 polymorphism were 36.8% [31-43%]
and 35.0% [29-41%]; the G allele frequencies (95% CI) of the LEPR rs1137100
polymorphism were 24.8% [19-30%] and 22.8% [18-28%]; the G allele frequencies
(95% CI) of the LEPR rs1137101 polymorphism were 43.6% [37-50%] and 42.9% [37
49%]; the G allele frequencies (95% CI) of the PPARg rs1801282 polymorphism were
7.6% [4-11%] and 8.3% [5-12%]; and the C allele frequencies (95% CI) of the
TCF7L2 rs7901695 polymorphism were 33.6% [28-39%] and 39.0% [33-45%],
respectively. Conclusion: The studied polymorphisms were not associated with GDM
in a Brazilian population.
PMID- 28699989
TI - Deaths related to differentiated thyroid cancer: a rare but real event.
AB - Objective: The present study describes the clinical and tumor characteristics of
patients that died from differentiated thyroid cancer and reports on the cause
and circumstances of death in these cases. Subjects and methods: Retrospective
analysis of all the differentiated thyroid cancer (DTC) related deaths at a
single institution over a 5-year period, with a total of 33 patients. Results:
Most of the patients were female (63.6%), with a mean age at diagnosis of 58.2
years. The most common histologic type was papillary (66.7%) and 30.3% were
follicular. The distribution according to the TNM classification was: 15.4% of
T1; 7.7% T2; 38.4% T3; 19.2% of T4a and 19.2% of T4b. Forty-four percent of cases
were N0; 20% N1a and 36.6% of N1b. Twelve patients were considered non-responsive
to radioiodine. Only one of the patients did not have distant metastases. The
most common metastatic site was the lung in 69.7%. The majority of deaths were
due to pulmonary complications related to lung metastases (17 patients, 51.5%),
followed by post-operative complications in 5 cases, neurological disease
progression in 3 cases, local invasion and airway obstruction in one patient.
Median survival between diagnosis and death was reached in 49 months while
between disease progression and death it was at 22 months. Conclusion: Mortality
from DTC is extremely rare but persists, and the main causes of death derive from
distant metastasis, especially respiratory failure due to lung metastasis. Once
disease progression is established, median survival was only 22 months.
PMID- 28699990
TI - Likelihood of malignancy in thyroid nodules according to a proposed Thyroid
Imaging Reporting and Data System (TI-RADS) classification merging suspicious and
benign ultrasound features.
AB - Objective: The aim of this study was to describe the ultrasound features of
benign and malignant thyroid nodules and evaluate the likelihood of malignancy
associated with each feature according to the Bethesda System for Reporting
Thyroid Cytopathology and histopathology. With this analysis, we propose a new TI
RADS classification system. Materials and methods: The likelihood of malignancy
from ultrasound features were assessed in 1413 thyroid nodules according to the
Bethesda System for Reporting Thyroid Cytopathology and histopathological
findings. A score was established by attributing different weights to each
ultrasound feature evaluated. Results: Features positively associated with
malignancy in bivariate analysis received a score weight of +1. We attributed a
weight of +2 to features which were independently associated with malignancy in a
multivariate analysis and +3 for those associated with the highest odds ratio for
malignancy (> 10.0). Hence, hypoechogenicity (graded as mild, moderate or marked,
according to a comparison with the overlying strap muscle), microcalcification
and irregular/microlobulated margin received the highest weights in our scoring
system. Features that were negatively associated with malignancy received weights
of -2 or -1. In the proposed system a cutoff score of 2 (sensitivity 97.4% and
specificity 51.6%) was adopted as a transition between probably benign (TI-RADS
3) and TI-RADS 4a nodules. Overall, the frequency of malignancy in thyroid
nodules according to the categories was 1.0% for TI-RADS 3, 7.8% for TI-RADS 4a,
35.3% for TI-RADS 4b, and 84.7% for TI-RADS 5. Conclusion: A newly proposed TI
RADS classification adequately assessed the likelihood of malignancy in thyroid
nodules.
PMID- 28699991
TI - Factors influencing the missed nursing care in patients from a private hospital.
AB - Objective: to determine the factors that influence the missed nursing care in
hospitalized patients. Methods: descriptive correlational study developed at a
private hospital in Mexico. To identify the missed nursing care and related
factors, the MISSCARE survey was used, which measures the care missed and
associated factors. The care missed and the factors were grouped in global and
dimension rates. For the analysis, descriptive statistics, Spearman's correlation
and simple linear regression were used. Approval for the study was obtained from
the ethics committee. Results: the participants were 71 nurses from emergency,
intensive care and inpatient services. The global missed care index corresponded
to M=7.45 (SD=10.74); the highest missed care index was found in the dimension
basic care interventions (M=13.02, SD=17.60). The main factor contributing to the
care missed was human resources (M=56.13, SD=21.38). The factors related to the
care missed were human resources (rs=0.408, p<0.001) and communication (rs=0.418,
p<0.001). Conclusions: the nursing care missed is mainly due to the human
resource factor; these study findings will permit the strengthening of nursing
care continuity.
PMID- 28699992
TI - Changes in frailty conditions and phenotype components in elderly after
hospitalization.
AB - Objective:: describing the changes in frailty conditions over the period of a
year after hospital discharge, verifying predictive variables for changes in
frailty conditions and frailty phenotype components according to worsening,
improving and stable groups. Method:: a longitudinal survey carried out with 129
elderly. A structured form for socioeconomic and health data, scales (Geriatric
Depression Scale - short form, Katz scale, Lawton and Brody scale) and frailty
phenotype according to Fried were used. Descriptive analysis and multinomial
logistic regression model (p<0.05) were performed. Results:: we found that 56.7%
of older adults changed their condition from non-frail to pre-frail, with no
changes from non-frail to frail. Deaths were found between frail and pre-frail
elderly. In the worsening group, the increase in the number of morbidities was a
predictor for exhaustion and/or fatigue, while in the improving group, increased
dependence on instrumental activities of daily living was a predictor for weight
loss, and reduced scores indicative of depression due to low level of physical
activity. Conclusion:: a greater percentage of changes from non-frail condition
to pre-frail older adults were observed, and health variables were only
predictive for frailty phenotype components. Objetivo:: descrever as mudancas nas
condicoes de fragilidade ao longo de um ano apos a alta hospitalar, e verificar
as variaveis preditoras da mudanca das condicoes de fragilidade e dos componentes
do fenotipo de fragilidade, segundo grupos de piora, melhora e estabilidade.
Metodo:: inquerito longitudinal, realizado com 129 idosos. Utilizou-se formulario
estruturado para dados socioeconomicos e saude, escalas (Depressao Geriatrica
Abreviada, Katz, Lawton e Brody) e fenotipo de fragilidade, segundo Fried.
Procederam-se as analises descritiva e modelo de regressao logistica multinomial
(p<0,05). Resultados:: constatou-se que 56,7% dos idosos mudaram sua condicao de
nao frageis para pre-frageis, nao ocorrendo mudanca dos nao frageis para frageis.
Observou-se o obito entre idosos frageis e pre-frageis. No grupo de piora, o
aumento do numero de morbidades foi preditor para exaustao e/ou fadiga, enquanto
que, no grupo de melhora, o aumento na dependencia das atividades instrumentais
de vida diaria foi preditor para a perda de peso, e a diminuicao dos escores do
indicativo de depressao para o baixo nivel de atividade fisica. Conclusao:: houve
maior percentual de mudanca na condicao de idosos nao frageis para pre-frageis e
as variaveis de saude foram preditoras apenas para os componentes do fenotipo de
fragilidade. Objetivo:: describir los cambios en las condiciones de fragilidad a
lo largo de un ano despues del alta hospitalaria, y verificar las variables
predictoras del cambio de las condiciones de fragilidad y de los componentes del
fenotipo de fragilidad, segun grupos de empeoramiento, mejoria y estabilidad.
Metodo:: encuesta longitudinal, realizada con 129 ancianos. Se utilizo formulario
estructurado para recoger datos socioeconomicos y salud; se utilizaron las
escalas Depresion Geriatrica Abreviada (GDS-15), Actividades Basicas de Vida
Diaria de Katz, Actividades Instrumentales de Vida Diaria de Lawton y Brody, y
Fenotipo de Fragilidad, segun Fried. Se procedio al analisis descriptivo y modelo
de regresion logistica multinomial (p<0,05). Resultados:: se constato que 56,7%
de los ancianos cambiaron su condicion de no-fragiles para prefragiles, no
habiendo ocurriendo cambio de los no-fragiles para fragiles. Se observo muerte
entre ancianos fragiles y prefragiles. En el grupo de empeoramiento, el aumento
del numero de morbilidades fue predictor para agotamiento y/o fatiga, en cuanto
en el grupo de mejoria, el aumento en la dependencia de las actividades
instrumentales de vida diaria fue predictor para la perdida de peso y la
disminucion de los puntajes del indicativo de depresion para el bajo nivel de
actividad fisica. Conclusion:: hubo mayor porcentaje de cambio en la condicion de
ancianos no-fragiles para prefragiles y las variables de salud fueron predictoras
apenas para los componentes del fenotipo de fragilidad.
PMID- 28699993
TI - Quality of life of patients using intermittent urinary catheterization.
AB - Objectives: measure and compare the quality of life of neurogenic bladder
patients using intermittent urinary catheterization who were going through
rehabilitation in Brazil and Portugal. Method: multicenter, quantitative, cross
sectional, observational-analytic and correlational study executed in Brazil and
Portugal. Two data collection tools were used, being one questionnaire with
sociodemographic and clinical data and the World Health Organization Quality of
Life-bref. Patients were included who were over 18 years of age, suffering from
neurogenic urinary bladder and using intermittent urinary catheterization.
Results: in the sample of Brazilian (n = 170) and Portuguese (n = 52) patients,
respectively, most patients were single (87-51.2%; 25-48.1%), had finished
primary education (47-45.3%; 31-59.6%) and were retired (70-41.2%; 21-40.4%).
Spinal cord injury was the main cause of using the urinary catheter in both
countries. The Brazilian patients presented higher mean quality of life scores in
the psychological domain (68.9) and lower scores in the physical domain (58.9).
The Portuguese patients presented higher scores in the psychological domain
(68.4) and lower scores in the environment domain (59.4). The execution of
intermittent urinary self-catheterization was significant for both countries.
Conclusions: in the two countries, these patients' quality of life can be
determined by the improvement in the urinary symptoms, independence, self
confidence, social relationships and access to work activities.
PMID- 28699994
TI - Safe surgery: validation of pre and postoperative checklists.
AB - Objective: to develop, evaluate and validate a surgical safety checklist for
patients in the pre and postoperative periods in surgical hospitalization units.
Method: methodological research carried out in a large public teaching hospital
in the South of Brazil, with application of the principles of the Safe Surgery
Saves Lives Programme of the World Health Organization. The checklist was applied
to 16 nurses of 8 surgical units and submitted for validation by a group of eight
experts using the Delphi method online. Results: the instrument was validated and
it was achieved a mean score >=1, level of agreement >=75% and Cronbach's alpha
>0.90. The final version included 97 safety indicators organized into six
categories: identification, preoperative, immediate postoperative, immediate
postoperative, other surgical complications, and hospital discharge. Conclusion:
the Surgical Safety Checklist in the Pre and Postoperative periods is another
strategy to promote patient safety, as it allows the monitoring of predictive
signs and symptoms of surgical complications and the early detection of adverse
events.
PMID- 28699995
TI - Procedures for measuring and verifying gastric tube placement in newborns: an
integrative review.
AB - Objective:: to investigate evidence in the literature on procedures for measuring
gastric tube insertion in newborns and verifying its placement, using alternative
procedures to radiological examination. Method:: an integrative review of the
literature carried out in the Cochrane, LILACS, CINAHL, EMBASE, MEDLINE and
Scopus databases using the descriptors "Intubation, gastrointestinal" and
"newborns" in original articles. Results:: seventeen publications were included
and categorized as "measuring method" or "technique for verifying placement".
Regarding measuring methods, the measurements of two morphological distances and
the application of two formulas, one based on weight and another based on height,
were found. Regarding the techniques for assessing placement, the following were
found: electromagnetic tracing, diaphragm electrical activity, CO2 detection,
indigo carmine solution, epigastrium auscultation, gastric secretion aspiration,
color inspection, and evaluation of pH, enzymes and bilirubin. Conclusion:: the
measuring method using nose to earlobe to a point midway between the xiphoid
process and the umbilicus measurement presents the best evidence. Equations based
on weight and height need to be experimentally tested. The return of secretion
into the tube aspiration, color assessment and secretion pH are reliable
indicators to identify gastric tube placement, and are the currently indicated
techniques. Objetivo:: investigar, na literatura, evidencias sobre procedimentos
de mensuracao da sonda gastrica em recem-nascidos e de verificacao do seu
posicionamento, procedimentos alternativos ao exame radiologico. Metodo:: revisao
integrativa da literatura nas bases Biblioteca Cochrane, LILACS, CINAHL, EMBASE,
MEDLINE e Scopus, utilizando os descritores "intubacao gastrointestinal" e "recem
nascido" em artigos originais. Resultados:: dezessete publicacoes foram incluidas
e categorizadas em "metodo de mensuracao" ou "tecnica de verificacao do
posicionamento". Como metodos de mensuracao, foram encontrados os de tomada de
duas distancias morfologicas e os de aplicacao de duas formulas, uma baseada no
peso e outra na altura. Para tecnicas de verificacao do posicionamento, encontrou
se tracado eletromagnetico, atividade eletrica do diafragma, deteccao de CO2,
solucao de indigo carmim, ausculta do epigastrio, aspiracao de secrecao gastrica,
inspecao da cor, avaliacao de pH, enzimas e bilirrubina. Conclusao:: o metodo de
mensuracao que utiliza as medidas do nariz ao lobulo da orelha ao ponto medio
entre apendice xifoide e cicatriz umbilical apresenta melhores evidencias. As
equacoes baseadas em peso e altura necessitam ser testadas experimentalmente. O
retorno de secrecao na aspiracao da sonda, avaliacao da cor e do pH da secrecao
sao indicadores confiaveis na identificacao do posicionamento da sonda gastrica,
e sao as tecnicas atualmente indicadas. Objetivo:: investigar, en la literatura,
evidencias sobre procedimientos de medicion de la sonda gastrica en recien
nacidos y de verificacion de su posicionamiento, procedimientos alternativos al
examen radiologico. Metodo:: revision integradora de la literatura en las bases
Biblioteca Cochrane, LILACS, CINAHL, EMBASE, MEDLINE y Scopus, utilizando los
descriptores "intubacion gastrointestinal" y "recien nacido" en articulos
originales. Resultados:: diecisiete publicaciones fueron incluidas y
categorizadas en "metodo de medicion" o "tecnica de verificacion del
posicionamiento". Como metodos de medicion, fueron encontrados los de medida de
dos distancias morfologicas y los de aplicacion de dos formulas (una basada en el
peso y otra en la altura). Para las tecnicas de verificacion del posicionamiento,
se encontro: trazado electromagnetico, actividad electrica del diafragma,
deteccion de CO2, solucion de indigo carmin, auscultacion del epigastrio,
aspiracion de secrecion gastrica, inspeccion del color, evaluacion de pH, enzimas
y bilirrubina. Conclusion:: el metodo de medicion que utiliza las medidas de la
nariz al lobulo de la oreja al punto medio entre apendice xifoideo y cicatriz
umbilical, presenta las mejores evidencias. Las ecuaciones basadas en peso y
altura necesitan ser comprobadas experimentalmente. El retorno de secrecion en la
aspiracion de la sonda, evaluacion del color y del pH de la secrecion son
indicadores confiables en la identificacion del posicionamiento de la sonda
gastrica, y son las tecnicas actualmente indicadas.
PMID- 28699996
TI - Quality of life and religious-spiritual coping in palliative cancer care
patients.
AB - Objectives: to compare the quality of life and religious-spiritual coping of
palliative cancer care patients with a group of healthy participants; assess
whether the perceived quality of life is associated with the religious-spiritual
coping strategies; identify the clinical and sociodemographic variables related
to quality of life and religious-spiritual coping. Method: cross-sectional study
involving 96 palliative outpatient care patient at a public hospital in the
interior of the state of Sao Paulo and 96 healthy volunteers, using a
sociodemographic questionnaire, the McGill Quality of Life Questionnaire and the
Brief Religious-Spiritual Coping scale. Results: 192 participants were
interviewed who presented good quality of life and high use of Religious
Spiritual Coping. Greater use of negative Religious-Spiritual Coping was found in
Group A, as well as lesser physical and psychological wellbeing and quality of
life. An association was observed between quality of life scores and Religious
Spiritual Coping (p<0.01) in both groups. Male sex, Catholic religion and the
Brief Religious-Spiritual Coping score independently influenced the quality of
life scores (p<0.01). Conclusion: both groups presented high quality of life and
Religious-Spiritual Coping scores. Male participants who were active Catholics
with higher Religious-Spiritual Coping scores presented a better perceived
quality of life, suggesting that this coping strategy can be stimulated in
palliative care patients.
PMID- 28699997
TI - Accuracy of a pediatric early warning score in the recognition of clinical
deterioration.
AB - Objective: to evaluate the accuracy of the version of the Brighton Pediatric
Early Warning Score translated and adapted for the Brazilian context, in the
recognition of clinical deterioration. Method: a diagnostic test study to measure
the accuracy of the Brighton Pediatric Early Warning Score for the Brazilian
context, in relation to a reference standard. The sample consisted of 271
children, aged 0 to 10 years, blindly evaluated by a nurse and a physician,
specialists in pediatrics, with interval of 5 to 10 minutes between the
evaluations, for the application of the Brighton Pediatric Early Warning Score
for the Brazilian context and of the reference standard. The data were processed
and analyzed using the Statistical Package for the Social Sciences and
VassarStats.net programs. The performance of the Brighton Pediatric Early Warning
Score for the Brazilian context was evaluated through the indicators of
sensitivity, specificity, predictive values, area under the ROC curve, likelihood
ratios and post-test probability. Results: the Brighton Pediatric Early Warning
Score for the Brazilian context showed sensitivity of 73.9%, specificity of
95.5%, positive predictive value of 73.3%, negative predictive value of 94.7%,
area under Receiver Operating Characteristic Curve of 91.9% and the positive post
test probability was 80%. Conclusion: the Brighton Pediatric Early Warning Score
for the Brazilian context, presented good performance, considered valid for the
recognition of clinical deterioration warning signs of the children studied.
PMID- 28699998
TI - Culture-bound syndromes in migratory contexts: the case of Bolivian immigrants.
AB - Objective: to describe the culture-bound syndromes maintained by Bolivian
immigrants in the new migratory context and analyze the care processes of these
health problems. Method: qualitative research with an ethnographic methodological
approach. Sample: 27 Bolivian immigrants. In-depth interviews and participatory
observation were the strategies used for data collection. Data were classified
and categorized into logical schemes manually and using the ATLAS-ti program v.5.
Results: susto, "wayras", amartelo, pasmo de sol, pasmo de luna and pasmo de
sereno are some of the folk illnesses that affect the Bolivian immigrants and
that they have to treat in the new migratory context. Conclusions: in the new
environment, the group under study preserves culture-bound syndromes that are
common in their country of origin. The care strategies used for these health
problems are adapted to the resources of the new context and based on
interactions with the domestic environment, biomedicine and traditional medicine.
It was observed the need for the health professionals to realize that the
efficacy of certain therapies occurs within the scope of cultural beliefs and not
in that of the scientific evidence.
PMID- 28699999
TI - Detection of zoonotic and livestock-specific assemblages of Giardia duodenalis in
free-living wild lizards.
AB - Giardia duodenalis is a zoonotic parasite that infects the gut of a wide range of
vertebrates, including numerous wildlife species. However, little is known about
this protozoan parasite in reptiles. Fecal samples from 31 wild lizards were
collected in Galicia (northwest Spain) and screened for the presence of Giardia
by PCR amplification and sequencing of the ITS1-5.8S-ITS2 region in the ribosomal
unit. This allowed detection of the parasite in 5 samples (16.1%), and enabled
identification of G. duodenalis assemblage A2 in two samples of Iberian rock
lizard (Iberolacerta monticola), G. duodenalis assemblage B in other two samples
of I. monticola, and G. duodenalis assemblage E in one sample of Bocage's wall
lizard (Podarcis bocagei). The results obtained after PCR amplification and
sequencing of the SSU-rDNA gene confirmed the presence of G. duodenalis
assemblage A in two samples of I. monticola. This is the first report of G.
duodenalis in free-living lizards, although further studies are needed to
distinguish between actual infection and mechanical dissemination of cysts. The
detection of zoonotic and livestock-specific assemblages of G. duodenalis
demonstrates the wide environmental contamination by this parasite, possibly due
to human activities.
PMID- 28700000
TI - Ticks infesting captive and free-roaming wild animal species at the Sao Paulo
Zoo, Sao Paulo, Brazil.
AB - Ticks are ectoparasites of worldwide distribution that affect vertebrates and can
transmit pathogens to animals and humans. The Zoological Park Foundation of Sao
Paulo (FPZSP) is located in a Conservation Unit in one of the most important
remaining fragments of the Atlantic Rainforest biome in the suburbs of Sao Paulo,
Brazil. The FPZSP houses more than 3,000 wild animals on exhibit, in breeding
programs and in environmental education programs, and also attracts migratory
birds and free-roaming wildlife. This study focused on identifying the diversity
of tick species that infest captive and free-roaming animals at the FPZSP. The
collection of ticks kept at the FPZSP contains 523 specimens that were collected
from different host species between 1990 and 2017. Ten tick species were found.
In addition, Amblyomma aureolatum (Pallas) was found on stray cats living in the
Atlantic forest fragment in the FPZSP. This study reveals a low occurrence of
parasitism in captive animals and a high diversity of tick species collected from
hosts in this Atlantic forest fragment, contributing information about host
parasite relationships and potential vectors of zoonotic diseases, since the
vectors of Brazilian spotted fever, A. aureolatum and Amblyomma sculptum Berlese,
were found in some hosts.
PMID- 28700001
TI - Genetic variability of Leishmania infantum in naturally infected dogs in the
state of Bahia, Brazil.
AB - In Brazil, Leishmania infantum mainly affects humans and dogs. The state of Bahia
presents many dogs that are positive for this parasite. Despite the importance of
epidemiology in this region, there are still very few studies that have assessed
the genetic characteristics of L. infantum. The aim of this study is to
investigate the genetic variability of L. infantum isolated identified in
naturally infected dogs, in order to verify occurrence of subpopulation of this
parasite in the different biomes existing in the state of Bahia. Thirty-two
samples of L. infantum were analyzed, which were obtained isolated in dogs from
the Mata Atlantica (rainforest), Caatinga (semi-arid scrub forest), and Cerrado
(a vast tropical savannah eco-region) Bahia municipalities' biomes. All animals
presented with clinical changes suggestive of Leishmania spp. and they exhibited
positive reactions to serological tests. kDNA analysis with RFLP markers revealed
the presence of genetic variability and gene flow in subpopulations of L.
infantum; samples from the Mata Atlantica areas were genetically more similar to
those from the areas of Caatinga and they were less likely to resemble those of
the Cerrado. This data may be used to investigate the dissemination of parasite
in the canine population of state of Bahia.
PMID- 28700002
TI - Evaluation of silybum marinaum efficacy on University of Wisconsin and histidine
tryptophan-ketoglutarate solutions latter the damage of the perfused liver.
AB - Purpose: : To investigate the hepatoprotective and antioxidant effeicacies of
Silybum marianum's (silymarin, S) on University of Wisconsin (UW) and
histidinetryptophan-ketoglutarate (HTK) preservation solutions. Methods: : Thirty
two Wistar albino adult male rats were used. Group 1: UW group, Group 2: UW +
Silymarin group(S), Group 3: HTK group, Group 4: HTK + silymarin group (S),
respectively. Silymarin was enforced intraperitoneally before the surgery.
Biopsies were enforced in 0, 6 and 12.hours to investigate. Results: :
Biochemical parameters examined in alanine aminotransferase (ALT), furthermore
superoxide dismutase (SOD), catalase (CAT), and malondialdehyde (MDA) in rats
were also evaluated. Detected histopathological changings were substantially
declining in the groups that received silymarin, cellular damage was decreased
significantly in HTK + Silymarin group, according to other groups. It has been
identified as the most effective group was HTK + silymarin group in evaluation of
ALT, electron microscopic results, also decreased MDA and elevated in SOD, and
CAT activity. Caspase 3 analysis showed a substantial lower apoptosis ratio in
the silymarin groups than in the non-performed groups (p<0.05). Conclusion: :
Histidinetryptophan-ketoglutarate+silymarin group provides better
hepatoprotection than other groups, by decreasing the hepatic pathologic damage,
delayed changes that arise under cold ischemic terms.
PMID- 28700003
TI - The effects of chitosan oligosaccharides on OPG and RANKL expression in a rat
osteoarthritis model.
AB - Purpose: : To investigate the effect of chitosan oligosaccharides (COS) against
osteoarthritis (OA) and preliminarily discuss the osteoprotegerin (OPG), receptor
activator of NF-kappaB ligand (RANKL) and RANK expression in a rat OA model.
Methods: : Thirty-six 6-week-old Male SD rats were randomly divided into three
groups: sham-operated group(CON), OA-induction group(OA), COS intervention
group(n=12/group). At 4 weeks after the operation, COS (50 ul) intervention
weekily for consecutive 5 weeks. The OA and CON groups received an injection of
50 ul physiological saline. At death, 11 weeks following surgery, cartilage was
harvested and total RNA and protein were extracted. Both the morphological
changes of the cartilage were observed and harvested the total RNA and protein.
Meanwhile, the expression of OPG, RANKL and RANK in cartilage were determined.
Results: : The expression of OPG and RANKL were both enhanced in the cartilage of
the OA model. Compared with the OA group, COS treatment improved the cartilage
damage (both extent and grade). Furthermore, the COS group showed highly OPG and
lower RANKL. Simultaneously, COS treatment upregulated the ratio of OPG/RANKL and
downregulated the RANKL/RANK. Conclusion: : Chitosan oligosaccharides may be used
as a unique biological agent to prevent and treat osteoarthritis, and this effect
is associated with modulation of the expression of osteoprotegerin and receptor
activator of NF-kappaB ligand.
PMID- 28700004
TI - Dexmedetomidine protects against renal ischemia and reperfusion injury by
inhibiting the P38-MAPK/TXNIP signaling activation in streptozotocin induced
diabetic rats.
AB - Purpose: : To determine whether dexmedetomidine (DEX) could attenuate acute
kidney injury (AKI) induced by ischemia/reperfusion (I/R) in streptozotocin (STZ)
induced diabetic rats. Methods: : Four groups each containing six rats were
created (sham control(S), diabetes-sham (DS), diabetes I/R (DI/R), and diabetes
I/R-dexmedetomidine (DI/R-DEX). In diabetes groups, single-dose (65 mg/kg) STZ
was administered intraperitoneally (i.p.). In Group DI/R, ischemia reperfusion
was produced via 25 min of bilateral renal pedicle clamping followed by 48 h of
reperfusion. In Group DI/R-DEX, 50 MUg/kg dexmedetomidine was administered
intraperitoneally 30 minutes before ischemia. Renal function, histology,
apoptosis, the levels of TNF-alpha, IL-1beta, and oxidative stress in diabetic
kidney were determined. Moreover, expression of P38 mitogen-activated protein
kinase (P38-MAPK), phosphorylated-P38-MAPK(p-P38-MAPK) and thioredoxin
interacting protein (TXNIP) were assessed. Results: : The degree of renal I/R
injury was significantly increased in DI/R group compared with S group and DS
group. The levels of TNF-alpha, IL-1beta, oxidative stress and apoptosis were
found significantly higher in DI/R Group when compared with S Group and DS Group.
The protein expression of p-P38-MAPK and TXNIP were significantly increased after
I/R. All these changes were reversed by DEX treatment. Conclusion: : The
renoprotective effects of DEX-pretreatment which attenuates I/R-induced AKI were
partly through inhibition of P38-MAPK activation and expression of TXINP in
diabetic kidney.
PMID- 28700005
TI - Fluorescent test accurately predicts leak of ischemic colon anastomosis in rats.
AB - Purpose: : To investigate if fluorescein fluorescent test can predict dehiscence
in a model of ischemic colonic anastomosis in rats. Methods: : This experimental
controlled trial randomly assigned 55 rats to four groups. Anastomoses were
performed in non-ischemic colon segments (control group) and in ischemic colon
segments measuring 1, 2 or 3 cm long (groups 1, 2 and 3, respectively).
Fluorescein was injected and the tissues were examined under ultraviolet light.
Seven days later, a second-look surgery was performed to check for the presence
or absence of anastomosis dehiscence. Results: : Twenty-four rats presented
anastomotic dehiscence during the second-look surgery. Reticular and
nonfluorescent patterns were significantly associated with the occurrence of
anastomotic dehiscence. Fluorescein fluorescence had a sensitivity of 95.8%,
specificity of 89.2%, positive predictive value of 88.4%, negative predictive
value of 96.2%, and accuracy of 92.3% to predict anastomotic dehiscence.
Conclusion: : Fluorescein fluorescent test can accurately predict leak in a model
of ischemic colonic anastomosis in rats.
PMID- 28700006
TI - Effects of the essential oil of Alpinia zerumbet (Pers.) B.L. Burtt & R.M. Sm. on
healing and tissue repair after partial Achilles tenotomy in rats.
AB - Purpose: : To investigate the cellular response to injury, analyzing
histopathologic changes associated with increased cellularity, degeneration and
disorganization of collagen fibers. Methods: : Thirty wistar rats were divided in
two groups after partial Achilles tenotomy: the right hind paw were treated with
the essential oil of Alpinia zerumbet (EOAz), diluted to 33% (0.3 mL kg-1), and
the left hind paw received sunflower oil for 3, 14, 30 and 90 days. Statistical
significance was determined using a Chi-square and Pearson Correlation
qualitative variables test. Moreover, Mann-Whitney U-test test for comparison
between different groups of the same cell, one-way ANOVA, and Tukey's test of
quantitative measurement. Results: : A decrease hyperemia (p < 0.001) was
observed in the acute phase of inflammatory cell number (p < 0.001), whereas sub
acute phase was marked by significant correlation with macrophages in fibroblasts
(r = 0.17, p = 0.03), with probable induction a dense and modeled tissue. At
chronic phase, it was found an increase in the number of fibroblasts and a higher
percentage of type I collagen fibers (78%) compared with control collagen fibers
(55%). Conclusion: : Oil of Alpinia zerumbet stimulated the process of
maturation, organization and tissue repair which gave it greater resistance.
PMID- 28700007
TI - Impact of dexmedetomidine on amino acid contents and the cerebral ultrastructure
of rats with cerebral ischemia-reperfusion injury.
AB - Purpose: : To investigate the effects of dexmedetomidine (DEX) on amino acid
contents and the cerebral ultrastructure of rats with cerebral ischemia
reperfusion injury (I/R). Methods: : Thirty-six, male, Wistar rats were randomly
divided into three groups: the sham operation group (group C), the ischemia
reperfusion group (group I/R), and the DEX group (group D). The middle cerebral
artery occlusion model was prepared by the modified Longa method. The time of
ischemia was 180 min, and 120 min after reperfusion, the amount of glutamate
(Glu), and gamma-aminobutyric acid (GABA) in the brain were measured, and the
ultrastructure-level changes in the cerebral cortex were examined using electron
microscopy. Results: : Compared to group C, Glu contents in group D, and I/R
significantly increased. Compared to group I/R, Glu contents in group D
significantly decreased. Compared to group C, GABA contents in group D, and I/R
significantly increased, and those in group D significantly increased, as
compared to group I/R. The cerebral ultrastructure was normal in group C.
Vacuolar degeneration in the plastiosome and nervous processes, was more critical
than in group D. Vascular endothelial cells (VEC) were damaged. On the contrary,
these changes in group D significantly improved. Conclusion: : Dexmedetomidine is
capable of decreasing glutamergic content, and increasing GABAergic content, in
order to decrease the injury of the cerebral ultrastructure, following cerebral
ischemia-reperfusion injury.
PMID- 28700008
TI - Animal model of continuous peritoneal lavage with vacuum peritoneostomy.
AB - Purpose: : To establish and evaluate the feasibility of continuous peritoneal
lavage with vacuum peritoneostomy in an animal model. Methods: : Eight pigs aged
3-4 months, females, were anesthetized and submitted to laparotomy and
installation of a continuous peritoneal lavage with vacuum peritoneostomy. The
sta-bility of the system, the physiological effects of washing with NaCl 0.9% and
the sys-tem clearance were evaluated. Results: : Stability of vacuum
peritoneostomy was observed, with no catheter leaks or obstructions and the
clearance proved adequate, however, the mean volume of fluids aspirated by the
peritoneostomy at the end of the experiment was higher than the volume infused by
the catheters (p=0.02). Besides that, the animals presented a progressive
increase in heart rate (p=0.04) and serum potassium (p=0.02). Conclusion: : The
continuous peritoneal lavage technique with vacuum peritoneostomy is feasible and
presents adequate clearance.
PMID- 28700009
TI - Comparative study of pain in women submitted to conventional laparoscopic
cholecystectomy versus single-port laparoscopic cholecystectomy.
AB - Purpose: : To evaluate postoperative pain in patients submitted to conventional
laparoscopic cholecystectomy with four ports versus single-port laparoscopic
cholecystectomy with only one port. Methods: : Twenty-one patients were included
in the conventional laparoscopic cholecystectomy group and 19 other patients in
the single-port laparoscopic cholecystectomy group. A VAS was used for the
assessment of postoperative pain at three time points. Differences were
considered statistically significant when p<0.05. Results: : Intergroup analysis
showed no significant difference in VAS scores between the conventional
laparoscopic cholecystectomy and single-port laparoscopic cholecystectomy groups
at any of the time points studied. Conclusion: : This study found no significant
difference in postoperative pain between the two groups.
PMID- 28700010
TI - Argon plasma versus electrofulguration in the treatment of anal and perianal
condylomata acuminata in patients with acquired immunodeficiency virus.
AB - Purpose: : To compare the effectiveness of anal and perianal condylomata
treatment using argon plasma and electrofulguration. Methods: : From January 2013
to April 2014, 37 patients with anal and perianal condylomata, who had been
diagnosed through proctological examination, oncotic cytology, polymerase chain
reaction (PCR) and histology, underwent treatment with argon plasma and
electrofulguration. The perianal and anal regions were divided into two
semicircles. Each semicircle was treated using one of the methods by means of
simple randomization. Therapeutic sessions were repeated until all clinical signs
of infection by HPV were eliminated. The patients were evaluated according to
several variables like the genotype of HPV, HIV infection, oncological potential
per genotype, oncotic cytology and histology. Results: : Among all the variables
studied, only immunosuppression due to HIV influenced the results, specifically
when the fulguration method was used. There was no significant difference in
effectiveness between argon and fulguration based on lesion relapse (p > 0.05).
However, among HIV-positive patients, fulguration presented worse results, with a
significant difference (p = 0.01). Conclusion: : Regarding treatment of anal and
perianal condylomata acuminata, comparison between applying fulguration and argon
demonstrated that these methods were equivalent, but use of fulguration presented
more relapses among HIV-positive patients.
PMID- 28700011
TI - How does practice improve the skills of medical students during consecutive
training courses?
AB - Purpose: : To follow-up the development of medical students in taking a stitch
using two different bench models, and to assess their performance with regards to
gender, handedness, prior recreational activities and interest in surgery.
Methods: : The study was performed during the compulsory basic (n=152) and the
consecutive elective course (n=27). Students took simple interrupted stitches
into synthetic and biopreprate models in the classroom and in the operating room.
The time needed for that was measured and the quality was scored, using an OSATS
(Objective Structured Assessment of Technical Skill) checklist that had been
adapted to our training programs. Results: : Students' performance improved both
in time and quality during classes, over the course and compared basic to the
elective course, too. No significant difference was found in relation to gender
and handedness but certain recreational activities and special interest in
surgery led to better results. Operating room environment had a slight negative
effect on students' performance. Conclusion: : The study could provide objective
skill assessment, monitoring has revealed deficiencies and influencing factors.
Objective feedback, valid and reliable assessment is important in teaching
surgical skills. In addition it may contribute to higher surgical safety later on
in the clinical practice.
PMID- 28700012
TI - Amphetamine-type stimulant use and conditional paths of consumption: data from
the Second Brazilian National Alcohol and Drugs Survey.
AB - Objective:: The aim of this study was to estimate nationally representative
prevalence rates of amphetamine-type stimulant (ATS) use and to identify
consumption-associated factors, proposing a conditional model of direct and
indirect consumption paths. Method:: Using data from the Second Brazilian
National Alcohol and Drugs Survey, this cross-sectional study analyzed a
subsample of 3,828 participants between 15 and 64 years old, gathering
information on the use of psychoactive substances in a probabilistic sample of
the Brazilian household population. Results:: Rates of lifetime and last-year ATS
use were, respectively, 4.1 and 1.6%. Economically privileged individuals and
users of other substances were more at risk for using ATS. The results suggest
that higher education decreases the chances of ATS consumption. The conditional
model showed that higher income increased ATS use, higher education lowered the
odds of such an increase, and cocaine use cancelled that associative effect.
Conclusion:: Brazil presents high rates of ATS use. Prevention and treatment
strategies should focus on the protective effect of higher education levels and
should target polydrug use. Knowledge of ATS-associated factors and user profiles
is the starting point for developing effective treatments and tailored prevention
strategies.
PMID- 28700013
TI - Correlations between caregiver psychiatric symptoms and offspring psychopathology
in a low-resource setting.
AB - OBJECTIVE: Associations between parental/caregiver depression and adverse child
outcomes are well established and have been described through one or more
mechanisms: child psychopathology following exposure to a depressed caregiver,
child psychopathology exacerbating a caregiver's depression, and caregiver and
offspring depression sharing the same etiology. Data from low and middle-income
countries is scarce. We examined correlations between common symptoms of mental
disorders in caregivers and their offspring's psychopathology in a Brazilian
sample. METHODS: In this cross-sectional study, adult caregivers were screened
for depression during routine home visits by community health workers as part of
the Brazilian Family Health Strategy. Caregivers with suspected depression were
assessed using the Zung Self-Rating Depression Scale and the Self-Reporting
Questionnaire (SRQ-20). Children's symptoms were evaluated using the Strengths
and Difficulties Questionnaire (SDQ). RESULTS: The sample included 68 primary
caregivers and 110 children aged 6 to 15 years. Higher caregiver scores on the
SRQ-20 correlated significantly with psychiatric symptoms in offspring.
CONCLUSION: These results substantiate our hypothesis that child psychopathology
correlates with caregivers' psychiatric symptoms. This paper adds to the growing
literature on community mental health assessment and can help guide future
strategies for reducing the burden of common mental disorders in caregivers and
children alike in low and middle-income countries.
PMID- 28700014
TI - Predictors of length of stay in an acute psychiatric inpatient facility in a
general hospital: a prospective study.
AB - OBJECTIVE: There have been significant reductions in numbers of psychiatric beds
and length of stay (LOS) worldwide, making LOS in psychiatric beds an interesting
outcome. The objective of this study was to find factors measurable on admission
that would predict LOS in the acute psychiatric setting. METHODS: This was a
prospective, observational study. RESULTS: Overall, 385 subjects were included.
The median LOS was 25 days. In the final model, six variables explained 14.6% of
the variation in LOS: not having own income, psychiatric admissions in the
preceding 2 years, high Clinical Global Impression and Brief Psychiatric Rating
Scale scores, diagnosis of schizophrenia, and history of attempted suicide. All
variables were associated with longer LOS, apart from history of attempted
suicide. CONCLUSIONS: Identifying patients who will need to stay longer in
psychiatric beds remains a challenge. Improving knowledge about determinants of
LOS could lead to improvements in the quality of care in hospital psychiatry.
PMID- 28700015
TI - Telomere length and hTERT in mania and subsequent remission.
AB - OBJECTIVE: The findings of telomere length (TL) studies in bipolar disorder (BD)
are controversial. The aim of the present study was to detect TL, human
telomerase reverse transcriptase (hTERT), and brain derived neurotrophic factor
(BDNF) in severe mania and subsequent remission. METHODS: Twenty-one medication
free male patients and 20 age and gender matched controls were recruited. The
patients were followed in the inpatient clinic, and comparisons were made between
the same patients in their remission state and controls. Patients received
lithium plus antipsychotics during the follow-up period. Quantitative real-time
polymerase chain reaction was performed to verify leukocyte TL and whole blood
hTERT gene expression levels. Serum BDNF levels were verified by enzyme-linked
immunosorbent assay (ELISA). RESULTS: Compared to controls, manic patients
presented shorter telomeres (p < 0.001) whose length increased with treatment (p
= 0.001). Patients in the late stages showed shorter TL than those in the early
stages and controls (p < 0.001). hTERT gene expression levels were up-regulated
in mania and remission compared to controls (p = 0.03 and p = 0.01,
respectively). BDNF changes did not reach statistically significant levels.
CONCLUSIONS: TL and hTERT gene expression might reflect a novel aspect of BD
pathophysiology and TL might represent a novel biomarker for BD staging.
PMID- 28700016
TI - Primary Mitral Valve Regurgitation Outcome in Patients With Severe Aortic
Stenosis 1 Year After Transcatheter Aortic Valve Implantation: Echocardiographic
Evaluation.
AB - Background:: Mitral valve regurgitation (MR), present in up to 74% of the
patients with severe aortic stenosis (AS), can be a negative prognostic factor
when moderate or severe. The outcome of MR after percutaneous transcatheter
aortic valve implantation (TAVI) and predictors associated with that outcome have
not been well established in the literature. Objective:: To assess the outcome of
primary MR in patients submitted to TAVI and to identify associated factors.
Methods:: Observational study of patients with symptomatic severe AS submitted to
TAVI from January 2009 to April 2015 at two specialized centers.
Echocardiographic outcome was assessed with data collected before and 1 year
after TAVI. Results:: Of the 91 patients with MR submitted to TAVI and followed
up for at least 12 months, 67 (73.6%) had minimum/mild MR before the procedure
and 24 (26.4%) had moderate/severe MR. Of those with minimum/mild MR, 62 (92.5%)
had no change in the MR grade (p < 0.001), while 5 (7.5%) showed worsening. Of
those with moderate/severe MR, 8 (33.3%) maintained the same grade and 16 (66.7%)
improved it (p = 0.076). Patients with moderate/severe MR who improved MR grade
had lower EuroSCORE II (p = 0.023) and STS morbidity (p = 0.027) scores, as
compared to those who maintained the MR grade. Conclusion:: MR grades change
after TAVI. This study suggests a trend towards improvement in moderate/severe MR
after TAVI, which was associated with lower preoperative risk scores.
Fundamentos:: A insuficiencia valvar mitral (IM), presente em ate 74% dos
pacientes com estenose aortica (EA) grave, pode representar um fator prognostico
negativo quando moderada ou importante. A evolucao da IM apos implante percutaneo
de valva aortica transcateter (TAVI) e preditores associados a essa evolucao nao
estao bem estabelecidos na literatura. Objetivos: : Avaliar a evolucao da IM
primaria em pacientes submetidos ao TAVI e identificar fatores associados a essa
evolucao. Metodos: : Realizou-se um estudo observacional em pacientes com EA
grave sintomatica, submetidos ao TAVI no periodo de janeiro de 2009 a abril de
2015 em dois centros especializados. Foram avaliados desfechos ecocardiograficos
com dados antes e 1 ano apos a intervencao. Resultados: : Dos 91 pacientes com IM
que realizaram TAVI e tinham acompanhamento de pelo menos 12 meses, 67 (73,6%)
apresentavam IM minima ou discreta antes da realizacao do procedimento e 24
(26,4%), IM moderada ou grave. Entre os com IM minima ou discreta, 62 (92,5%) nao
apresentaram mudanca no grau de refluxo (p < 0,001) e 5 (7,5%) tiveram piora.
Entre os com IM moderada ou grave, 8 (33,3%) permaneceram na mesma classe e 16
(66,7%) tiveram melhora (p = 0,076). Pacientes com IM moderada ou grave que
melhoraram o grau de insuficiencia apresentavam menores valores de EuroSCORE II
(p = 0,023) e STS morbidade (p = 0,027), quando comparados aos que continuaram na
mesma classe. Conclusao: : Observou-se mudanca significativa no grau de IM apos
realizacao de TAVI. Este estudo sugere uma tendencia de melhora da IM moderada ou
grave apos TAVI, o que se associou a escores de risco pre-operatorios menos
elevados.
PMID- 28700017
TI - Plasma Total Antioxidant Capacity and Cardiometabolic Risk in Non-Obese and
Clinically Healthy Young Adults.
AB - Background:: The oxidative biomarkers play an important role in the genesis of
cardiometabolic risk-related processes. Objective:: To investigate the total
antioxidant capacity of plasma and its association with cardiometabolic risk in
non-obese and clinically healthy young adults. Methods:: University students of
the state of Sergipe, Brazil, aged between 18 and 25 years, were recruited for
this study from May of 2013 and October of 2014. Anthropometric, clinical and
biochemical parameters were measured and analyzed using protocols which were
previously standardized and described in the literature. The measurement of
plasma total antioxidant capacity was based on the ability that all the
antioxidants present in the sample (plasma) have to inhibit the oxidation of the
oxidizable substrate ABTS (2,2'- Azino-di-[3-ethylbenzthiazoline sulphonate]) to
ABTS*+ by metmyoglobin. Results:: Approximately 25% of the sample presented more
than one component of cardiometabolic risk. Low HDL-cholesterol was the most
prevalent component. Compared to absence of components, the subjects with at
least one component presented greater body weight and waist circumference, higher
levels of diastolic blood pressure and fasting glucose, greater total
cholesterol/HDL-c ratio, and lower levels of HDL-c (p < 0.05). Fasting glycemia
was the only parameter which was associated with total antioxidant capacity (R2 =
0.10; beta = 0.17; p = 0.001). Conclusions:: The plasma total antioxidant
capacity was not able to predict the cardiometabolic risk components due possibly
to the establishment of compensatory mechanisms that become activated in
physiological conditions. Fundamentos:: Os biomarcadores oxidativos exercem um
importante papel na genese dos processos relacionados ao risco cardiometabolico.
Objetivo:: Investigar a capacidade antioxidante total do plasma e sua associacao
com risco cardiometabolico em adultos jovens, nao obesos e clinicamente
saudaveis. Metodos:: Estudantes universitarios do estado de Sergipe, Brasil, com
idade entre 18 e 25 anos, foram recrutados entre maio de 2013 e outubro de 2014.
Parametros antropometricos, clinicos e bioquimicos foram medidos e analisados
usando protocolos previamente padronizados e descritos na literatura. A medida da
capacidade antioxidante total do plasma baseou-se na capacidade de todos os
antioxidantes presentes na amostra (plasma) em inibir a oxidacao do substrato
oxidavel ABTS (2,2-Azino-bis-(3-etilbenzotiazolina-6-sulfonato) a ABTS*+ pela
metamioglobina. Resultados:: Aproximadamente 25% da amostra apresentaram mais de
um componente do risco cardiometabolico. Valores baixos de HDL foram o componente
mais prevalente. Em comparacao a ausencia de componentes, os individuos com pelo
menos um componente apresentou valores mais altos de peso corporal,
circunferencia da cintura, pressao sanguinea diastolica, glicemia de jejum e
razao colesterol total/HDL-c, e valores mais baixos de HDL-c (p < 0,05). A
glicemia de jejum foi o unico parametro que se associou com a capacidade
antioxidante total (R2 = 0,10; beta = 0,17; p = 0,001). Conclusoes:: A capacidade
antioxidante total nao foi capaz de predizer os componentes do risco
cardiometabolico possivelmente devido ao estabelecimento de mecanismos
compensatorios que se tornam ativados em condicoes fisiologicas.
PMID- 28700018
TI - Peripheral Vascular Resistance Impairment during Isometric Physical Exercise in
Normotensive Offspring of Hypertensive Parents.
AB - Background:: A family history of hypertension is associated with vascular and
autonomic abnormalities, as well as an impaired neurohemodynamic response to
exercise. Objective:: To test the hypothesis that normotensive individuals with a
family history of hypertension present an impaired peripheral vascular resistance
response to exercise. Methods:: The study included 37 normotensive volunteers of
both sexes who were sedentary, eutrophic, and nonsmokers, comprising 23 with
(FH+; 24 +/- 3 years) and 14 without (FH-; 27 +/- 5 years) a family history of
hypertension. Blood pressure, heart rate (DIXTAL(r)), forearm blood flow
(Hokanson(r)), and peripheral vascular resistance were simultaneously measured
for 3 minutes during rest and, subsequently, for 3 minutes during an isometric
exercise at 30% of maximal voluntary contraction (Jamar(r)). Results:: At rest,
the FH+ and FH- groups present similar mean blood pressure (83 +/- 7 versus 83 +/
5 mmHg, p = 0.96), heart rate (69 +/- 8 bpm versus 66 +/- 7 bpm, p = 0.18),
forearm blood flow (3 +/- 1 mL/min/100 mL versus 2.7 +/- 1 mL/min/100 mL, p =
0.16), and peripheral vascular resistance (30 +/- 9 units versus 34+/-9 units, p
= 0.21), respectively. Both groups showed a significant and similar increase in
mean blood pressure (? = 15 +/- 7 mmHg versus 14 +/- 7 mmHg, p = 0.86), heart
rate (? = 12 +/- 8 bpm versus 13 +/- 7 bpm, p = 0.86), and forearm blood flow (?
= 0.8 +/- 1.2 mL/min/100 mL versus 1.4 +/- 1.1 mL/min/100 mL, p = 0.25),
respectively, during exercise. However, individuals in the FH+ group showed no
reduction in peripheral vascular resistance during exercise, which was observed
in the FH- group (? = -0.4 +/- 8.6 units versus -7.2 +/- 6.3 units, p = 0.03).
Conclusion:: Normotensive individuals with a family history of hypertension
present an impaired peripheral vascular resistance response to exercise.
Fundamento:: O historico familiar para hipertensao arterial esta relacionado a
anormalidades vasculares e autonomicas, bem como disfuncoes no comportamento
neuro-hemodinamico durante o exercicio fisico. Objetivo:: Testar a hipotese de
que individuos normotensos com historico familiar de hipertensao arterial
apresentam resposta prejudicada da resistencia vascular periferica durante o
exercicio fisico. Metodos:: Foram avaliados 37 normotensos de ambos os sexos,
sedentarios, eutroficos e nao tabagistas, sendo 23 com historico familiar
positivo (HF+, 24 +/- 3 anos) e 14 com historico familiar negativo (HF-, 27 +/- 5
anos) para hipertensao arterial. Foram identificados pressao arterial, frequencia
cardiaca (DIXTAL(r)), fluxo sanguineo muscular do antebraco e resistencia
vascular periferica local (Hokanson(r)) por 3 minutos durante o repouso e, em
seguida, 3 minutos durante exercicio isometrico de preensao palmar a 30% da
contracao voluntaria maxima (Jamar(r)). Resultados:: Em repouso, os grupos HF+ e
HF- apresentaram valores semelhantes de pressao arterial media (83 +/- 7 mmHg
versus 83 +/- 5 mmHg, p = 0,96), frequencia cardiaca (69 +/- 8 bpm versus 66 +/-
7 bpm, p = 0,18), fluxo sanguineo muscular (3 +/- 1 mL/min/199 mL versus 2,7 +/-
1 mL/min/100 mL, p = 0,16) e resistencia vascular periferica (30 +/- 9 unidades
versus 34 +/- 9 unidades, p = 0,21), respectivamente. Durante o exercicio, HF+ e
HF- mostraram aumento significativo e semelhante da pressao arterial media (? =
15 +/- 7 mmHg versus 14 +/- 7 mmHg, p = 0,86), frequencia cardiaca (? = 12 +/- 8
bpm versus 13 +/- 7 bpm, p = 0,86) e fluxo sanguineo muscular (? = 0,8 +/- 1,2
mL/min/100 mL versus 1,4 +/- 1,1 mL/min/100 mL, p = 0,25), respectivamente.
Entretanto, no grupo HF+ nao houve reducao significativa da resistencia vascular
periferica durante o exercicio, fato que ocorreu no grupo HF- (? = -0,4 +/- 8,6
unidades versus -7,2 +/- 6,3 unidades, p = 0,03). Conclusao:: Individuos
normotensos com historico familiar de hipertensao arterial apresentam resposta
prejudicada da resistencia vascular periferica durante o exercicio fisico.
PMID- 28700019
TI - Assessment of Subclinical Doxorubicin-induced Cardiotoxicity in a Rat Model by
Speckle-Tracking Imaging.
AB - Backgrounds:: Despite their clear therapeutic benefits, anthracycline-induced
cardiotoxicity is a major concern limiting the ability to reduce morbidity and
mortality associated with cancers. The early identification of anthracycline
induced cardiotoxicity is of vital importance to assess the cardiac risk against
the potential cancer treatment. Objective:: To investigate whether speckle
tracking analysis can provide a sensitive and accurate measurement when detecting
doxorubicin-induced left ventricular injury. Methods:: Wistar rats were divided
into 4 groups with 8 rats each, given doxorubicin intraperitoneally at weekly
intervals for up to 4 weeks. Group 1: 2.5 mg/kg/week; group 2: 3 mg/kg/week;
group 3: 3.5mg/kg/week; group 4: 4mg/kg/week. An additional 5 rats were used as
controls. Echocardiographic images were obtained at baseline and 1 week after the
last dose of treatment. Radial (Srad) and circumferential (Scirc) strains, radial
(SRrad) and circumferential (SRcirc) strain rates were analyzed. After the
experiment, cardiac troponin I (cTnI) was analyzed and the heart samples were
histologically evaluated. Results:: After doxorubicin exposure, LVEF was
significantly reduced in group 4 (p = 0.006), but remained stable in the other
groups. However, after treatment, Srads were reduced in groups 2, 3 and 4 (p all
< 0.05). The decrease in Srads was correlated with cTnI (rho = -0.736, p = 0.000)
and cardiomyopathy scores (rho = -0.797, p = 0.000). Conclusion:: Radial strain
could provide a sensitive and noninvasive index in early detection of doxorubicin
induced myocardial injury. The changes in radial strain had a significant
correlation with myocardial lesions and serum cardiac troponin I levels,
indicating that this parameter could accurately evaluate cardiotoxicity severity.
Fundamento:: Apesar dos seus claros beneficios terapeuticos, a cardiotoxicidade
induzida pela antraciclina e uma grande preocupacao que limita a capacidade de
reduzir a morbidade e mortalidade associadas com canceres. A identificacao
precoce da cardiotoxicidade induzida por antraciclina e de vital importancia para
o equilibrio entre o risco cardiaco e o potencial tratamento do cancer.
Objetivo:: Investigar se a analise por speckle-tracking pode fornecer uma medida
sensivel e precisa na deteccao de lesao ventricular esquerda induzida por
doxorrubicina. Metodos:: Ratos Wistar foram divididos em 4 grupos de 8 ratos
cada, e doxorrubicina foi administrada intraperitonealmente em intervalos
semanais de ate 4 semanas. Grupo 1: 2,5 mg/kg/semana; Grupo 2: 3 mg/kg/semana;
Grupo 3: 3,5 mg/kg/semana; Grupo 4: 4 mg/kg/semana. Foram utilizados 5 ratos
adicionais como controles. As imagens ecocardiograficas foram obtidas na linha
basal e 1 semana apos a ultima dose do tratamento. Foram analisados o strain
radial (Srad) e circunferencial (Scirc) e as taxas de strain radial (TSrad) e
circunferencial (TScirc). Apos o experimento, a troponina cardiaca I (cTnI) foi
analisada e as amostras cardiacas foram avaliadas histologicamente. Resultados::
Apos a exposicao a doxorrubicina, a FEVE foi significativamente reduzida no grupo
4 (p = 0,006), mas permaneceu estavel nos outros grupos. Entretanto, apos o
tratamento, os Srads foram reduzidos nos grupos 2, 3 e 4 (p < 0,05). A diminuicao
dos Srads foi correlacionada com cTnI (rho = -0,736, p = 0,000) e os escores de
cardiomiopatia (rho = -0,797, p = 0,000). Conclusao:: O strain radial pode
fornecer um indice sensivel e nao-invasivo na deteccao precoce da lesao
miocardica induzida pela doxorrubicina. As alteracoes do strain radial
apresentaram correlacao significativa com lesoes miocardicas e niveis sericos de
troponina I cardiaca, indicando que esse parametro pode avaliar com precisao a
gravidade da cardiotoxicidade.
PMID- 28700020
TI - A Meta-Analysis of Circulating Microvesicles in Patients with Myocardial
Infarction.
AB - Background:: Cell-derived microvesicles (MVs) are vesicles released from
activated or apoptotic cells. However, the levels of MVs in myocardial infarction
have been found inconsistent in researches. Objective:: To assess the association
between MVs and myocardial infarction by conducting a meta-analysis. Methods:: A
systematic literature search on PubMed, Embase, Cochran, Google Scholar
electronic database was conducted. Comparison of the MVs levels between
myocardial infarction patients and healthy persons were included in our study.
Standard Mean Difference (SMD) and 95% confidence interval (CI) in groups were
calculated and meta-analyzed. Results: : 11 studies with a total of 436
participants were included. Compared with the health persons, AMVs [SMD = 3.65,
95% CI (1.03, 6.27)], PMVs [SMD = 2.88, 95% CI (1.82, 3.93),] and EMVs [SMD =
2.73, 95% CI (1.13, 4.34)], levels were higher in patients with myocardial
infarction. However, LMVs levels [SMD = 0.73, 95% CI (-0.57, 2.03)] were not
changed significantly in patients with myocardial infarction. Conclusions: :
AMVs, PMVs and EMVs might be potential biomarkers for myocardial infarction.
Fundamentos: : As microvesiculas derivadas de celulas (MVs) sao vesiculas
liberadas de celulas ativadas ou apoptoticas. No entanto, os niveis de MVs no
infarto do miocardio foram encontrados inconsistentes nas pesquisas. Objetivo: :
Avaliar a associacao entre MV e infarto do miocardio por meio de uma meta
analise. Metodos: : Foi realizada uma pesquisa sistematica na literatura em
PubMed, Embase, Cochran e no banco de dados eletronico do Google Scholar. Uma
comparacao dos niveis de MV entre pacientes com infarto do miocardio e pessoas
saudaveis foi incluida no nosso estudo. A Diferenca Media Padrao (DMP) e o
intervalo de confianca (IC) de 95% nos grupos foram calculadas e meta-analisadas.
Resultados: : Foram incluidos 11 estudos com um total de 436 participantes. Em
comparacao com as pessoas saudaveis, as MVA [DMP = 3,65, IC 95% (1,03, 6,27)],
MVPs [DMP = 2,88, IC 95% (1,82, 3,93)] e MVEs [DMP = 2,73, IC 95% (1,13, 4.34)],
foram maiores em pacientes com infarto do miocardio. No entanto, os niveis de MVL
[DMP = 0,73, IC 95% (-0,57, 2,03)] nao foram alterados significativamente em
pacientes com infarto do miocardio. Conclusoes: : MVAs, MVPs e MVEs podem ser
biomarcadores potenciais para o infarto do miocardio.
PMID- 28700021
TI - Nursing management practicum: impact to the team in medical-surgical units.
AB - Objective: Learn the perceptions of nursing professionals of a university
hospital regarding the interactive process with nursing management practicum
students. Methods: A qualitative, exploratory, descriptive study was conducted by
means of 11 semi-structured interviews with nurses, nursing technicians and
nursing aides in medical-surgical units. The information, collected between
December 2013 and January 2014, was submitted to a thematic analysis and
discussed according to Pichon-Riviere. Results: Results were grouped into three
categories: Practicum students and the nursing team: interaction that can provide
learning, mutual help and satisfaction; Despite the pre-task, work must go on;
and Nursing team: the practicum facilitator. Conclusion: In the beginning, their
coexistence was full of basic anxieties, but while elaborating these feelings,
the group was created and shifts into teamwork. In this logic, issues like
patience, empathy, communication and coherence facilitate the interactive
process, and are essential for a critical (re)reading of the reality.
PMID- 28700022
TI - Permanent education in healthcare services: educational activities developed in
the state of Minas Gerais, Brazil.
AB - Objective: To analyse educational activities carried out in the state of Minas
Gerais, Brazil, considered permanent education in healthcare. Method: This is a
mixed methods study with a qualitative approach and the participation of 492
municipal health departments. Data were collected in March and October 2014
through interviews available online. The data were tabulated using Excel
software. The data were subjected to thematic content analysis and statistic
descriptive analysis. The study was approved with opinion 22830812.5.0000.5149.
Results: Data analysis revealed the following nine categories: type of practice,
theme, method, technological resource, motive, healthcare level, public,
financing, and status of the described practice. The activities were not related
to a specific educational concept. The researchers found that the subjects that
motivated the education activities were based on work and the diagnosis of
problems faced by the workers. These principles are characteristic of permanent
education in healthcare. Conclusion: In some municipalities, permanent education
is being incorporated into the healthcare service routine.
PMID- 28700023
TI - Patient safety in the understanding of health care students.
AB - Objective: To verify the understanding of graduate health care students on
patient safety. Method: Descriptive cross study, held in 2015 with 638 students
at the Health Sciences Center of the Federal University of Santa Maria, State of
Rio Grande do Sul, Brazil. The study used a questionnaire with variables related
to the characterization of students, the conceptual and attitudinal aspects of
human error and patient safety, made available online in the Student Portal.
Results: A higher percentage of students reported having no formal training on
the subject. The study revealed aspects conside4red fundamental to the safety
culture, such as the importance of systemic error analysis, the concern with the
work environment and appreciation of teamwork. Some attitudes demonstrated
uncertainty in the correct way of acting. Conclusion: Students showed perceptions
that were favorable to patient safety. The formalization of the subject at
different levels of education is needed.
PMID- 28700024
TI - Accuracy of nursing diagnosis "readiness for enhanced hope" in patients with
chronic kidney disease.
AB - Objective: To analyse the accuracy of the nursing diagnosis readiness for
enhanced hope in patients with chronic kidney disease. Method: This is a cross
sectional study with 62 patients in the haemodialysis clinic conducted from
August to November 2015. The Hearth Hope Scale was used to create definitions of
the defining characteristics of the North American Nursing Diagnosis Association
International. We analysed the measures of sensitivity, specificity, predictive
value, likelihood ratio, and odds ratio of the defining characteristics of the
diagnosis. Results: Of the characteristics, 82.22% presented the diagnosis. The
defining characteristics "Expresses the desire to enhance congruency of
expectations with desires" and "Expresses the desire to enhance problem solving
to meet goals" increased the chance of having the diagnosis by eleven and five,
respectively. Conclusion: The characteristics, "Expresses desire to enhance
congruency of expectations with desires" and "Expresses desire to enhance problem
solving to meet goals" had good accuracy measures.
PMID- 28700025
TI - Association of social and clinical conditions to the quality of life of patients
with heart failure.
AB - Objective: To analyze the association between sociodemographic and clinical
conditions with the quality of life related to health of heart failure patients.
Method: Cross-sectional study with a non-random sample of 84 outpatients with
heart failure, performed in the city of Joao Pessoa, PB, Brazil, in the period
from January to July 2015. The questionnaire by name Minnesota Living with Heart
Questionnaire was used The following tests were applied in data analysis: t
Student, ANOVA and Pearson's Correlation, com a 5% significance level. Results:
The average scores of the Minnesota Living with Heart Failure Questionnaire
showed a good quality of life in the group under study. There was a significant
negative association between quality of life and age: thus the lower the age, the
worse the quality of life. Conclusion: Health promotion actions become necessary
to improve the coping capacity of this disease, especially for younger patients.
PMID- 28700026
TI - Self-inflicted violence by exogenous poisoning in an emergency service.
AB - Objective: To analyze the self-inflicted violence by exogenous poisoning reported
in a health service. Methods: Epidemiological, retrospective and analytical study
in an emergency care in the city of Teresina, Piaui. The study took place in
January and February of 2015, upon review of all cases of self-inflicted violence
by exogenous poisoning reported to the Information System on Diseases of
Compulsory Declaration, from 2009 to 2014. The Pearson chi-square test was used
for analysis. Results: 277 victims of self-inflicted violence by exogenous
poisoning were reported, with 10.5% having died by suicide. There was an
association between death and the age, education, area of occurrence and type of
exposure, as well as between the type of exposure and the amount of agents used.
Conclusion: The results help to define prevention strategies considering
vulnerable groups and the complexity of the factors associated with self
inflicted violence.
PMID- 28700027
TI - Life on Facebook: self-care in renal transplantation patients.
AB - Objective: To analyze self-care in renal transplantation patients. Methods:
Qualitative research, inspired in the post-structuralism. The empirical material
was composed by the posts of a Facebook group of Renal Transplantation Patients,
collected from February to May of 2016, totaling 53 posts from 35 participants.
The research data were analyzed under the perspective of cultural analysis, using
theories derived from Foucault. Results: Self-care in renal transplantation
patients was identified by the preoccupation with themselves and others, habits
and lifestyles, restrictions and limitations that the disease imposes, such as
lessons, ways of living and lifestyles after the procedure. Conclusions: This
experience forces people that have been submitted to renal transplantation to
reflect on the lifestyle they follow. The group also stimulates adhesion to
treatment.
PMID- 28700028
TI - Characteristics of the phenomenological interview in nursing research.
AB - Objective: To reflect on the characteristics of the phenomenological interview as
part of a phenomenological research in nursing research and to present some
practical recommendations for its realization. Method: Reflective theoretical
study conducted in October and November of 2016 about the development of the
phenomenological interview in nursing, based on the scientific literature and
critical analysis of the authors. Results: We present the characteristics of the
phenomenological interview and suggest some practical recommendations for its
application in nursing. Conclusions: The interview is a valuable tool to access
the phenomenon studied in nursing and unveiled by being.
PMID- 28700029
TI - Ethos and pathos in the delivery room.
AB - Objective: To understand the ethos and pathos in the discourses of pregnant women
and healthcare professionals in the context of the delivery room. Method: This is
a qualitative and interpretative study. The research approach was discourse
analysis. The study participants were 36 women and 24 health workers from seven
maternity hospitals in midwestern Minas Gerais, Brazil. Results: The discourses
indicate the notion the women have of childbirth, centered in the eyes of others
and in their representations. The nurses have difficulty operationalising care
and building a professional image. The medical discourse stresses the skills, the
ability to intervene in high-risk situations, and changes in the status of the
profession. Conclusions: The construction of the ethos of physicians and nurses
to essential to design more flexible fields of knowledge and ensure a
professional performance that is consistent with their role, committed to the
ethical and legal issues of obstetric care.
PMID- 28700030
TI - Risk for adverse reaction to iodinated contrast media: a validation study.
AB - Objectives: To validate the content of the nursing diagnosis, Risk for adverse
reaction to iodinated contrast media, and its nursing interventions and outcomes
according to standardized terminologies. Method: Fehring's (1987) model of
diagnosis content validation was used, with the participation of experts
including registered nurses and physicians. Results: Seventy-four experts
validated the title and the definition of the diagnosis, and assessed 28 risk
factors, five of which were validated as primary, 22 as secondary, and one was
discarded. The inclusion of the diagnosis in the NANDA International Taxonomy II
was evaluated by 41 registered nurses and validated for Area II - Safety/
Protection and Class 2 - Physical Injury. Sixty-three experts validated seven
nursing interventions as primary and one as secondary, and seven nursing outcomes
as principal and one as minor. Conclusion: The title, definition, and risk
factors of the diagnosis were validated, in addition to eight interventions and
eight nursing outcomes.
PMID- 28700031
TI - Inhibitory effect of the Pseudobrickellia brasiliensis (Spreng) R.M. King & H.
Rob. aqueous extract on human lymphocyte proliferation and IFN-gamma and TNF
alpha production in vitro.
AB - Pseudobrickellia brasiliensis (Asteraceae) is a plant commonly known as arnica-do
campo and belongs to the native flora of the Brazilian Cerrado. The alcoholic
extract of the plant has been used as an anti-inflammatory agent in folk
medicine, but the biological mechanism of action has not been elucidated. The
present study evaluated the composition of P. brasiliensis aqueous extract and
its effects on pro-inflammatory cytokine production and lymphocyte proliferation.
The extracts were prepared by sequential maceration of P. brasiliensis leaves in
ethanol, ethyl acetate, and water. Extract cytotoxicity was evaluated by trypan
blue exclusion assay, and apoptosis and necrosis were measured by staining with
annexin V-FITC and propidium iodide. The ethanolic (ETA) and acetate (ACE)
extracts showed cytotoxic effects. The aqueous extract (AQU) was not cytotoxic.
Peripheral blood mononuclear cells stimulated with phorbol myristate acetate and
ionomycin and treated with AQU (100 MUg/mL) showed reduced interferon (IFN)-gamma
and tumor necrosis factor (TNF)-alpha expression. AQU also inhibited lymphocyte
proliferative response after nonspecific stimulation with phytohemagglutinin. The
aqueous extract was analyzed by liquid chromatography coupled with photodiode
array detection and mass spectrometry. Quinic acid and its derivatives 5
caffeoylquinic acid and 3,5-dicaffeoylquinic acid, as well as the flavonoids
luteolin and luteolin dihexoside, were detected. All these compounds are known to
exhibit anti-inflammatory activity. Taken together, these findings demonstrate
that P. brasiliensis aqueous extract can inhibit the pro-inflammatory cytokine
production and proliferative response of lymphocytes. These effects may be
related to the presence of chemical substances with anti-inflammatory actions
previously reported in scientific literature.
PMID- 28700032
TI - Lipoprotein(a) as a predictor of poor collateral circulation in patients with
chronic stable coronary heart disease.
AB - As a mechanism compensating for obstructive coronary artery disease, coronary
collateral circulation (CCC) has attracted cardiologists for a long time to
explore its potential impact. In the present study, Chinese patients suffering
from >=95% coronary stenosis, as diagnosed by angiography, have been investigated
for the correlation between CCC and lipoprotein(a) [Lp(a)] levels. A cohort of
654 patients was divided into four categories according to Rentrop grades 0, 1,
2, and 3. Lp(a) levels were divided into model 1, discretized with critical
values of 33 and 66%, and model 2, discretized with a cutoff value of 30.0 mg/dL.
Furthermore, we evaluated the correlation between CCC and serum Lp(a) levels. The
four groups had significantly different Lp(a) levels (25.80+/-24.72, 18.99+/
17.83, 15.39+/-15.80, and 8.40+/-7.75 mg/dL; P<0.001). In model 1, concerning R0,
the risk in the third Lp (a) tertile (OR=3.34, 95%CI=2.32-4.83) was greater than
that in the first tertile. In model 2, concerning R0, the risk in Lp(a) >30.0
group (OR=6.77, 95%CI=4.44-10.4) was greater than that of Lp(a) <30.0 mg/dL. The
worst condition of CCC can be predicted independently by Lp(a) levels. In
addition to clinical usage, Lp(a) levels can also be utilized as biological
markers.
PMID- 28700033
TI - Astragalus polysaccharides improve cardiomyopathy in STZ-induced diabetic mice
and heterozygous (SOD2+/-) knockout mice.
AB - Oxidative stress plays an important role in the development of diabetic
cardiomyopathy. In the present study, we determined whether the effect of
astragalus polysaccharides (APS) on diabetic cardiomyopathy was associated with
its impact on oxidative stress. Streptozotocin (STZ)-induced diabetic mice and
heterozygous superoxide dismutase (SOD2+/-) knockout mice were administered APS.
The hemodynamics, cardiac ultrastructure, and the apoptosis, necrosis and
proliferation of cardiomyocytes were assessed to evaluate the effect of APS on
diabetic and oxidative cardiomyopathy. Furthermore, H2O2 formation, oxidative
stress/damage, and SOD activity in cardiomyocytes were evaluated to determine the
effects of APS on cardiac oxidative stress. APS therapy improved hemodynamics and
myocardial ultrastructure with reduced apoptosis/necrosis, and enhanced
proliferation in cardiomyocytes from both STZ-induced diabetic mice and
heterozygous SOD2+/- knockout mice. In addition, APS therapy reduced H2O2
formation and oxidative stress/damage, and enhanced SOD activity in both groups
of mice. Our findings suggest that APS had benefits in diabetic cardiomyopathy,
which may be partly associated with its impact on cardiac oxidative stress.
PMID- 28700034
TI - Application of endoscopy to treat mandibular keratocystic odontogenic tumors.
AB - The aim of this study was to evaluate the feasibility of endoscopy to remove
keratocystic odontogenic tumors (KCOTs) with virtual 3D mandibular images.
Fifteen patients (mean age, 40.27+/-14.58 years) who underwent endoscopic
mandibular KCOT enucleation between May 2009 and October 2009 were included.
Virtual 3D mandibular reconstructions derived from computed tomography (CT)
imaging were generated for all patients. Recurrence and pathological fracture
were evaluated as the primary outcome variables at 1 and 12 months after
operation. Secondary infection and inferior alveolar nerve injury were evaluated
as the secondary outcome variables at 1 and 6 months after operation. None of the
15 patients exhibited signs of recurrence or pathological fracture after
operation. During long-term follow-up, no symptoms of inferior alveolar nerve
injury or secondary infection were observed and no signs of recurrence were found
in any of the patients. Endoscopy helps surgeons to remove mandibular KCOTs with
small incisions. Moreover, endoscopy can provide clear and magnified views and
help to avoid damage to the inferior alveolar neurovascular bundle. Therefore,
under the support of preoperative virtual 3D mandibular images, the application
of endoscopy to remove the tumors should be considered to be a treatment option
for KCOTs.
PMID- 28700035
TI - Excavation of attractor modules for nasopharyngeal carcinoma via integrating
systemic module inference with attract method.
AB - The molecular mechanism of nasopharyngeal carcinoma (NPC) is poorly understood
and effective therapeutic approaches are needed. This research aimed to excavate
the attractor modules involved in the progression of NPC and provide further
understanding of the underlying mechanism of NPC. Based on the gene expression
data of NPC, two specific protein-protein interaction networks for NPC and
control conditions were re-weighted using Pearson correlation coefficient. Then,
a systematic tracking of candidate modules was conducted on the re-weighted
networks via cliques algorithm, and a total of 19 and 38 modules were separately
identified from NPC and control networks, respectively. Among them, 8 pairs of
modules with similar gene composition were selected, and 2 attractor modules were
identified via the attract method. Functional analysis indicated that these two
attractor modules participate in one common bioprocess of cell division. Based on
the strategy of integrating systemic module inference with the attract method, we
successfully identified 2 attractor modules. These attractor modules might play
important roles in the molecular pathogenesis of NPC via affecting the bioprocess
of cell division in a conjunct way. Further research is needed to explore the
correlations between cell division and NPC.
PMID- 28700036
TI - Computerized cognitive training in children and adolescents with attention
deficit/hyperactivity disorder as add-on treatment to stimulants: feasibility
study and protocol description.
AB - Background: Cognitive training has received increasing attention as a non
pharmacological approach for the treatment of attention deficit/hyperactivity
disorder (ADHD) in children and adolescents. Few studies have assessed cognitive
training as add-on treatment to medication in randomized placebo controlled
trials. The purpose of this preliminary study was to explore the feasibility of
implementing a computerized cognitive training program for ADHD in our
environment, describe its main characteristics and potential efficacy in a small
pilot study. Methods: Six ADHD patients aged 10-12-years old receiving stimulants
and presenting residual symptoms were enrolled in a randomized clinical trial to
either a standard cognitive training program or a controlled placebo condition
for 12 weeks. The primary outcome was core ADHD symptoms measured using the
Swanson, Nolan and Pelham Questionnaire (SNAP-IV scale). Results: We faced higher
resistance than expected to patient enrollment due to logistic issues to attend
face-to-face sessions in the hospital and to fill the requirement of medication
status and absence of some comorbidities. Both groups showed decrease in parent
reported ADHD symptoms without statistical difference between them. In addition,
improvements on neuropsychological tests were observed in both groups - mainly on
trained tasks. Conclusions: This protocol revealed the need for new strategies to
better assess the effectiveness of cognitive training such as the need to
implement the intervention in a school environment to have an assessment with
more external validity. Given the small sample size of this pilot study,
definitive conclusions on the effects of cognitive training as add-on treatment
to stimulants would be premature.
PMID- 28700037
TI - Perfectionism and negative/positive affect associations: the role of cognitive
emotion regulation and perceived distress/coping.
AB - Objective: To explore 1) if perfectionism, perceived distress/coping, and
cognitive emotion regulation (CER) are associated with and predictive of
negative/positive affect (NA/PA); and 2) if CER and perceived distress/coping are
associated with perfectionism and if they mediate the perfectionism-NA/PA
associations. There is a distinction between maladaptive and adaptive
perfectionism in its association with NA/PA. CER and perceived distress/coping
may mediate the maladaptive/adaptive perfectionism and NA/PA associations.
Methods: 344 students (68.4% girls) completed the Hewitt & Flett and the Frost
Multidimensional Perfectionism Scales, the Composite Multidimensional
Perfectionism Scale, the Profile of Mood States, the Perceived Stress Scale, and
the Cognitive Emotion Regulation Questionnaire. Results: NA predictors were
maladaptive/adaptive perfectionism, maladaptive CER and perceived distress
(positively), positive reappraisal and planning, and perceived coping
(negatively). PA predictors were maladaptive/adaptive perfectionism and perceived
distress (negatively), positive reappraisal and planning, positive refocusing and
perceived coping (positively). The association between maladaptive perfectionism
and NA was mediated by maladaptive CER/low adaptive CER, perceived distress/low
coping. Maladaptive perfectionism and low PA association was mediated by
perceived distress. High PA was determined by low maladaptive perfectionism and
this association was mediated by adaptive REC and coping. Adaptive perfectionism
and NA association was mediated by maladaptive CER and perceived distress.
Conclusion: CER and perceived distress/coping are associated and mediate the
perfectionism-NA/PA associations.
PMID- 28700038
TI - Eclectic approach to anxiety disorders among rural children.
AB - Introduction: Anxiety disorders in primary school-aged children negatively affect
their mental health and psychological development. Available non-medical
treatments for these conditions are time-consuming and expensive. In this
context, eclectic therapy is a therapeutic approach that incorporates some
therapeutic techniques and philosophies to create the ideal treatment. In this
study, eclectic therapy consisted of art therapy and cognitive-behavioral therapy
designed for children suffering from high level of anxiety in their middle
childhood years. The therapy also included group guidance sessions for their
mothers. The effectiveness of this intervention was examined in the study.
Methods: 61 students aged 9-12 years with high levels of anxiety participated in
the study. Intervention A (n = 20) consisted of 9-hour eclectic therapy for
children with 3-hour group guidance sessions for their mothers. Intervention B (n
= 20) consisted of 9-hour eclectic therapy for children. There was also a control
group (n = 21). Results: Teacher ratings of children's mental health difficulties
and self-report ratings of anxiety disorders indicated a significant difference
from pretest to posttest, revealing a large effect size between the two
interventions. Higher levels of pretest scores significantly predicted higher
posttest scores for all domains of anxiety and mental health difficulties.
Furthermore, age, gender, mothers working a 15-hour day, mother's educational
level, parental divorce rates, parental death, and family monthly income
predicted therapy outcomes. Conclusion: Results provide support for the
effectiveness of eclectic art and CBT to improve children's mental health and
reduce anxiety through changing thoughts, beliefs, emotions, and behaviors that
may cause fear and anxiety.
PMID- 28700039
TI - Sexual dysfunction in females with depression: a cross-sectional study.
AB - Introduction: Female sexual dysfunction (FSD) in depression albeit common is
strikingly understudied. The condition, if addressed properly, can be readily
cured, improving the quality of life of the patient. Methods: A consecutive
sample of drug-naive married female patients with depression was assessed.
Depression was diagnosed using the Structured Clinical Interview for DSM-IV Axis
I Disorders (SCID-I). Depression severity was assessed using the Hamilton
Depression Rating Scale (HAM-D), and sexual dysfunction, the Female Sexual
Function Index (FSFI). Results: Sexual dysfunction was found in 90% of the
patients in our study. Patients with medical comorbidities showed a significant
decrease in the desire subset of the FSFI (Mann-Whitney U=11.0, p=0.009), however
there was no significant association with other subsets. Patients who expressed
passive death wishes had higher scores on all indicators of sexual function and a
significantly higher score in the orgasm subset of the FSFI (Mann-Whitney U=11.0,
p=0.009). Conclusion: The study showed a high prevalence of FSD in depressed
females regardless of type and severity of depression. Depression with medical
comorbidities was associated with a significant decrease in desire. Patients who
expressed passive death wishes showed improved sexual function and significantly
better orgasm.
PMID- 28700040
TI - Translation and cross-cultural adaptation of the Sexual Function Questionnaire
(SFQ) into Brazilian Portuguese.
AB - Introduction: Sexual dysfunction is common in patients with psychotic illness.
This article describes the translation and cross-cultural adaptation of the
Sexual Function Questionnaire (SFQ) into Brazilian Portuguese. Methods: The
translation and cross-cultural adaptation followed the guidelines for adapting
self-report instruments proposed by the Task Force of the International Society
for Pharmacoeconomics and Outcomes Research (ISPOR). Briefly, ISPOR steps
include: preparation, forward translation, reconciliation, back-translation, back
translation review, harmonization, cognitive debriefing, review of cognitive
debriefing and finalization, before proofreading and final version. The original
authors authorized the translation and participated in the study. Results: There
was good agreement between translations and between the back-translation and the
original English version of the SFQ. The final version was prepared with
certificated evaluators in the original language and in Portuguese. Few changes
were necessary to the new version in Portuguese. Conclusion: The translated and
adapted Brazilian Portuguese version of the SFQ is reliable and semantically
equivalent to the original version. Studies on psychotropic-related sexual
dysfunction may now test the validity of the instrument and can investigate
sexual dysfunction in Portuguese-speaking patients.
PMID- 28700041
TI - Association between resilience and posttraumatic stress disorder among Brazilian
victims of urban violence: a cross-sectional case-control study.
AB - Introduction: This study investigated the association between resilience and
posttraumatic stress disorder (PTSD) among Brazilian victims of urban violence.
It also compared defense mechanisms, parental bonding, and childhood trauma
between those who developed PTSD and those who did not. Methods: This cross
sectional case-control study included 66 adult subjects exposed to recent urban
violence in southern Brazil - 33 with PTSD and 33 healthy controls matched by sex
and age - who were administered the Resilience Scale, Defense Style
Questionnaire, Parental Bonding Instrument, and Childhood Trauma Questionnaire.
The statistical tests used were the McNemar test for categorical variables, the
Wilcoxon signed-rank test for continuous asymmetric variables, and the paired
Student t-test for continuous symmetric variables. Results: The PTSD group showed
lower total Resilience Scale scores compared with controls (128.4+/-20.7 vs.
145.8+/-13.1, respectively; p = 0.01), along with a lower ability to solve
situations and lower personal values that give meaning to life (p = 0.019). They
also had lower rates of mature defense mechanisms (p < 0.001) and higher rates of
emotional (p = 0.001) and physical (p = 0.003) abuse during childhood.
Conclusion: Lower levels of resilience, especially the ability to solve
situations and having personal values that give meaning to life, immature defense
mechanisms, and emotional and physical abuse in childhood are associated with
PTSD in adult Brazilian victims of urban violence.
PMID- 28700042
TI - Posttraumatic stress disorder: a serious post-earthquake complication.
AB - Objectives: Earthquakes are unpredictable and devastating natural disasters. They
can cause massive destruction and loss of life and survivors may suffer
psychological symptoms of severe intensity. Our goal in this article is to review
studies published in the last 20 years to compile what is known about
posttraumatic stress disorder (PTSD) occurring after earthquakes. The review also
describes other psychiatric complications that can be associated with
earthquakes, to provide readers with better overall understanding, and discusses
several sociodemographic factors that can be associated with post-earthquake
PTSD. Method: A search for literature was conducted on major databases such as
MEDLINE, PubMed, EMBASE, and PsycINFO and in neurology and psychiatry journals,
and many other medical journals. Terms used for electronic searches included, but
were not limited to, posttraumatic stress disorder (PTSD), posttraumatic
symptoms, anxiety, depression, major depressive disorder, earthquake, and natural
disaster. The relevant information was then utilized to determine the
relationships between earthquakes and posttraumatic stress symptoms. Results: It
was found that PTSD is the most commonly occurring mental health condition among
earthquake survivors. Major depressive disorder, generalized anxiety disorder,
obsessive compulsive disorder, social phobia, and specific phobias were also
listed. Conclusion: The PTSD prevalence rate varied widely. It was dependent on
multiple risk factors in target populations and also on the interval of time that
had elapsed between the exposure to the deadly incident and measurement. Females
seemed to be the most widely-affected group, while elderly people and young
children exhibit considerable psychosocial impact.
PMID- 28700043
TI - Facing Chagas disease.
PMID- 28700044
TI - Prevalence of and risk factors for multidrug-resistant tuberculosis in Iran and
its neighboring countries: systematic review and meta-analysis.
AB - Tuberculosis, in particular drug-resistant tuberculosis, is of global concern due
to the high mortality and morbidity associated with it annually. The aim of this
study was to determine the prevalence of and the risk factors for multidrug
resistant tuberculosis in Iran and its neighboring countries. Four databases
(PubMed, BioMed Central, EMBASE, and Web of Science) were searched using key
terms. Nineteen eligible articles were identified, of which 12 and seven were
used for quantitative and qualitative analysis, respectively. The overall pooled
estimate of the prevalence of multidrug-resistant tuberculosis, including both
new and previously treated tuberculosis cases, in Iran, Iraq, Turkey and Pakistan
was 16% (95% confidence interval [CI] 11-20). The patients with a previous
tuberculosis treatment history (odds ratio [OR] = 6.45; 95% CI 5.12-7.79), those
aged <45 years (OR = 1.57; 95% CI 1.12-2.03), and those who were males (OR =
1.83; 95% CI 1.19-2.48) had an increased pool risk of developing multidrug
resistant tuberculosis. The forest plot revealed that the pooled odds for the
development of multidrug- resistant tuberculosis were 2.01 (95% CI 1.65-2.36).
Poor adherence to treatment was one of the predictors of unsuccessful treatment
outcomes. Multidrug-resistant tuberculosis is a great concern for public health
programs in many countries globally, including those included in this review. The
risk factors for the development of multidrug-resistant tuberculosis,
specifically a previous tuberculosis treatment history, should be targeted
through the implementation of specialized interventions.
PMID- 28700045
TI - Chagas disease: review of needs, neglect, and obstacles to treatment access in
Latin America.
AB - After more than one century since its discovery, Chagas disease is still
extremely prevalent in 21 Latin American countries. Chagas disease is one of the
most concerning public health problems in Latin America; the overall cost of CD
treatment is approximately 7 billion United States dollars per year and it has a
strong social impact on populations. Little progress has been made regarding the
access to diagnosis and treatment at the primary health care level, calling into
question the current policies to ensure the right to health and access to
essential medications. In this article, diverse dimensions of access to treatment
for Chagas disease are reviewed, illustrating the present state of benznidazole
medication in relation to global production capacity, costs, and needs. The
findings are based on an investigation requested by Medecins Sans Frontieres
Brazil through a consultancy in 2015, aiming to estimate the current costs of
benznidazole production.
PMID- 28700046
TI - Association between TGFbeta1 polymorphisms and chronic hepatitis B infection in
an Iranian population.
AB - INTRODUCTION: : Transforming growth factor-beta 1 (TGFbeta1) is a potent
suppressive cytokine that contributes to chronic hepatitis B (CHB) infection.
Disparities in TGFbeta1 production among individuals have been attributed to
TGFbeta1 genetic polymorphisms. We examined whether three putative polymorphisms
in TGFbeta1[-509 C/T (rs1800469), +869 C/T (rs1800470), and +11929 C/T
(rs1800472)]are associated with CHB infection in a South-Eastern Iranian
population. METHODS: : In total, 341 subjects were recruited, including 178
patients with CHB and 163 healthy individuals as controls. Genotyping of the
three TGFbeta1 SNPs was performed by tetra amplification refractory mutation
system-PCR. RESULTS: : TheTGFbeta1 +869 TT vs.CC genotype in codominant
(OR=0.445, p=0.012) and TT vs. TC+CC in the recessive (OR=0.439, p=0.003) model
as well as the variant allele T vs. C(OR=0.714, p=0.038) were associated with
lower CHB infection risk. However, the +11929 C/T polymorphism was associated
with increased CHB risk, and the CT vs. CC genotype (OR=2.77, P=0.001) and T
variant allele (OR=2.53, P=0.002) were risk factors for CHB. Furthermore, TTT
(+869/-509/+11929) and CCC haplotypes were risk and protective factors for CHB,
respectively. We found no significant association between viral DNA load and
TGFbeta1 genotype or hepatic enzyme levels (p >0.05). CONCLUSIONS: : Results
indicated that the TGFbeta1+869TT genotype and T allele were protective factors,
whereas the +11929 CT genotype and T allele were risk factors for CHB infection.
PMID- 28700047
TI - Influence of meteorological variables on dengue incidence in the municipality of
Arapiraca, Alagoas, Brazil.
AB - INTRODUCTION:: Meteorological influences along with the lack of basic sanitation
has contributed to disease outbreaks, resulting in large socio-economic losses,
especially in terms of dengue. This study aimed to evaluate the meteorological
influences on the monthly incidence of dengue in Arapiraca-AL, Brazil during 2008
2015. METHODS:: We used generalized linear models constructed via logistic
regression to assess the association between the monthly incidence of dengue
(MID) of and 8 meteorological variables [rainfall (R), air temperature (AT), dew
point temperature (DPT), relative humidity (RH), pressure surface, wind speed
(WS), wind direction (WD), and gust], based on data obtained from DATASUS and
meteorological station databases, respectively. The dengue-1 model included R,
AT, DPT, and RH and the dengue-2 model included AT, DPT, RH, WS, and WD. A MID
>100 (classified as moderate incidence) indicated an abnormal month. RESULTS::
Based on the dengue-1 model, variables with the highest odds ratio included R
lag1, DPT-lag1, and AT-lag1 with a 10.1, 18.3, and 26.7 times greater probability
of a moderate MID, respectively. Based on the dengue-2 model, variables with the
highest odds ratio were AT-lag1 and RH-lag0 indicating an 8.9 and 18.1 times
greater probability of a moderate MID, respectively. CONCLUSIONS:: AT, DPT, R, RH
and WS influenced the occurrence of a moderate MID.
PMID- 28700048
TI - Distribution of the bla OXA , bla VEB-1 , and bla GES-1 genes and resistance
patterns of ESBL-producing Pseudomonas aeruginosa isolated from hospitals in
Tehran and Qazvin, Iran.
AB - INTRODUCTION: : Pseudomonas aeruginosa is one of the most common nosocomial
pathogens. The emergence of extended spectrum beta-lactamases (ESBLs) has been
increasingly reported as a major clinical concern worldwide. The main aim of the
present study was to determine the distribution of bla OXA, bla PER-1, bla VEB-1,
and bla GES-1 genes among ESBL-producing P. aeruginosa isolated from two distinct
provinces in Iran. METHODS:: In this study, a total of 75 (27.5%) ESBL-producing
isolates were identified from 273 P. aeruginosa isolates collected from patients
in Qazvin and Tehran. Phenotypic detection of ESBLs and antimicrobial
susceptibility testing were performed according to the Clinical and Laboratory
Standards Institute guidelines. PCR and sequencing were employed to detect bla
OXA-1, bla OXA, bla GES-1, bla PER-1, and bla VEB-1 genes. Isolate genetic
relationships were evaluated by repetitive extragenic palindromic sequence-based
PCR (REP-PCR). RESULTS: : In total, 59 (78.7%) of the ESBL-producing isolates
showed multidrug resistance. The highest rates of susceptibility were observed
against colistin (75 isolates, 100%) and polymyxin B (75, 100%) followed by
amikacin (44, 58.7%), and piperacillin-tazobactam (40, 53.3%). The bla OXA-1
(37.3%) gene was the most common of the genes investigated, followed by bla OXA-4
(32%), bla GES-1 (16%), and bla VEB-1 (13.3%). REP-PCR identified three different
genotypes: types A (89.3%), B (6.7%), and C (4%). CONCLUSIONS:: We found a
significant presence of bla OXA-1, bla OXA-4, bla GES-1, and bla VEB-1 genes
among P. aeruginosa isolates, highlighting the need for suitable infection
control strategies to effectively treat patients and prevent the further
distribution of these resistant organisms.
PMID- 28700049
TI - Molecular detection of beta-lactamase and integron genes in clinical strains of
Klebsiella pneumoniae by multiplex polymerase chain reaction.
AB - INTRODUCTION:: Infections caused by beta-lactamase-producing gram-negative
bacteria, such as Klebsiella pneumoniae, are increasing globally with high
morbidity and mortality. The aim of the current study was to determine
antimicrobial susceptibility patterns and the prevalence of antibiotic resistance
genes (beta-lactamase and integron genes) using multiplex PCR. METHODS: One
hundred K. pneumoniae isolates were collected from different clinical samples.
Antibiotic susceptibility testing was performed with thirteen different
antibiotics. Multiplex-PCR was used to detect beta-lactamase (bla TEM, bla CTX-M,
bla SHV , bla VEB, bla PER, bla GES, bla VIM, bla IMP, bla OXA, and bla KPC) and
integron genes (int I, int II, and int III). RESULTS:: The highest and lowest
rate of resistance was exhibited against amikacin (93%) and imipenem (8%),
respectively. The frequency of beta-lactamase-positive K. pneumoniae was 37%, and
the prevalence of the bla TEM, bla CTX-M, bla SHV , bla VEB, bla PER, bla GES,
bla VIM, bla IMP, bla OXA, and bla KPC genes was 38%, 24%, 19%, 12%, 6%, 11%,
33%, 0%, 28%, and 23%, respectively. Of the 100 isolates, eight (8%) were
positive for class I integrons; however, class II and III integrons were not
detected in any of the strains. CONCLUSIONS:: These results indicate co-carriage
of a number of beta-lactamase genes and antibiotic resistance integrons on the
same plasmids harboring multi-drug resistance genes. It seems that these
properties help to decrease treatment complications due to resistant bacterial
infections by rapid detection, infection-control programs and prevention of
transmission of drug resistance.
PMID- 28700050
TI - Characterization of biofilm formation, antimicrobial resistance, and
staphylococcal cassette chromosome mec analysis of methicillin resistant
Staphylococcus hominis from blood cultures of children.
AB - INTRODUCTION:: Methicillin resistant Staphylococcus hominis (MRSHo) has been
recognized as an important human pathogen, particularly in immunocompromised
patients. METHODS:: A total of 19 S. hominis isolates were collected from
children at the Children's Medical Centre, Tehran, Iran, from March 2012 to
February 2013. MRSHo susceptibility against 13 antimicrobial and 3 antiseptic
agents was determined using disk diffusion (DAD) and minimum inhibitory
concentration (MIC), respectively. All isolates were subjected to polymerase
chain reaction (PCR) assay for 15 distinct resistance genes, staphylococcal
cassette chromosome mec (SCCmec), and arginine catabolic mobile elements (ACMEs).
Biofilm production of the isolates was determined using a colorimetric microtiter
plate assay. RESULTS: : Of the 19 isolates, 16 were resistant to oxacillin and
harbored mecA. High resistance was also observed against
trimethoprim/sulfamethoxazole (81.2%). All MRSHo isolates were susceptible to the
three disinfectants tested (Septicidine-PC, Septi turbo, and Sayacept-HP). In
total, 15 (78.9%) isolates produced biofilms. Three isolates had SCCmec types (V
and VIII), 13 were untypable (UT), and 5 had ACME type II. CONCLUSIONS:: The
results indicate that MRSHo with high antibiotic resistance and unknown SCCmec
might become a serious problem in the future for the treatment of patients such
as children.
PMID- 28700051
TI - Pharmacotherapeutic follow-up of patients with Chagas disease using benznidazole:
drug-related problems and pharmaceutical interventions.
AB - INTRODUCTION: Benznidazole (BNZ) is a drug available for the etiological
treatment of Chagas disease. However, this drug is toxic and has a limited
effectiveness on the chronic phase of this disease, often leading to poor
treatment adherence. METHODS:: This is a descriptive and exploratory study
conducted at the Pharmaceutical Care Service for Chagas disease patients of the
Federal University of Ceara. Drug-related problems (DRPs) and pharmaceutical
interventions (PIs) were classified according to the Second Consensus of Granada.
RESULTS:: The average age of patients with Chagas disease was 62 years, with the
majority residing in the Ceara countryside (86.7%), and having low education
levels (63.3% with elementary school education). Regarding family income, most
patients belonged to a household that earned <=1-2 times the minimum wage per
month. Approximately 73% of these patients complied with the BNZ treatment, and
nearly 7% underwent therapy interruption after medical evaluation. A total of 189
DRPs were identified, of which 51.9% (n=98) were classified as potential, and
48.1% (n=91) as actual. The most frequent DRPs were related to safety
(qualitative safety; n=70; 37%), necessity (non-adherence; n=52; 27.5%), and
effectiveness (qualitative effectiveness/non-optimal drug selection; n=45;
23.8%). Among the 216 PIs conducted, the majority were related to patient
education (n=168; 77.8%) and pharmacological strategy (n=42; 19.4%).
CONCLUSIONS:: This study indicates the need for pharmacotherapeutic monitoring in
patients with Chagas because of the high number of therapeutic interventions,
DRPs (approximately 3 DRPs/patient), BNZ adherence, and polypharmacy.
PMID- 28700052
TI - Influence of environmental enrichment on the behavior and physiology of mice
infected by Trypanosoma cruzi.
AB - INTRODUCTION:: Enriched environments normally increase behavioral repertoires and
diminish the expression of abnormal behaviors and stress-related physiological
problems in animals. Although it has been shown that experimental animals
infected with microorganisms can modify their behaviors and physiology, few
studies have evaluated how environmental enrichment affects these parameters.
This study aimed to evaluate the effects of environmental enrichment on the
behavior and physiology of confined mice infected with Trypanosoma cruzi.
METHODS:: The behaviors of 20 T. cruzi-infected mice and 20 non-infected mice
were recorded during three treatments: baseline, enrichment, and post-enrichment.
Behavioral data were collected using scan sampling with instantaneous recording
of behavior every 30s, totaling 360h. Plasma TNF, CCL2, and IL-10 levels and
parasitemia were also evaluated in infected enriched/non-enriched mice.
Behavioral data were evaluated by Friedman's test and physiological data by one
way ANOVA and area under the curve (AUC) analysis. RESULTS:: Results showed that
environmental enrichment significantly increased exploratory behaviors and
diminished inactivity. The use of environmental enrichment did not diminish
circulating levels of TNF and IL-10 but diminished circulating levels of CCL2 and
parasitemia. CONCLUSIONS:: Positive behavioral and physiological effects of
environmental enrichment were observed in mice living in enriched cages. Thus,
environmental enrichment improved the welfare of these animals.
PMID- 28700053
TI - Standardization and evaluation of a duplex real-time quantitative PCR for the
detection of Leishmania infantum DNA: a sample quality control approach.
AB - INTRODUCTION:: Molecular techniques have been shown to be alternative methods for
the accurate detection of infectious and parasitic diseases, such as the
leishmaniases. The present study describes the optimization and evaluation of a
duplex real-time quantitative PCR (qPCR) protocol developed for the simultaneous
detection of Leishmania infantum DNA and sample quality control. METHODS:: After
preliminary tests with the newly designed TaqMan(r) probes for the two targets (
L. infantum and glyceraldehyde 3-phosphate dehydrogenase (G3PD) gene), the duplex
qPCR protocol was optimized. For the evaluation of the standardized protocol,
human blood samples were tested (n=68) and the results were compared to those
obtained by reference diagnostic techniques. Statistical analyses included
percentage agreement and the Kappa ( k ) coefficient. RESULTS:: The detection
limit of L. infantum DNA reached 2x10 2 fg (corresponding to ~1 parasite) per uL
of blood (epsilon: 93.9%). The percentage agreement obtained between the duplex
VL qPCR and the reference techniques was individually obtained as follows:
molecular: 88.3% ( k =0.666; 95% CI 0.437-0.894, good), and serological: 81.7% (
k =0.411; 95% CI 0.125-0.697, moderate). Between the reference techniques, the
percentage agreement was 86.7% ( k =0.586; 95% CI 0.332-0.840, moderate).
CONCLUSIONS:: The new duplex VL qPCR protocol indicated good potential for the
accurate, fast, and reliable detection of L. infantum DNA, when applied as a
complement to the classical diagnostic tools already available, especially in
health or research reference centers.
PMID- 28700054
TI - Sensitivity and specificity of the circulating cathodic antigen rapid urine test
in the diagnosis of Schistosomiasis mansoni infection and evaluation of morbidity
in a low- endemic area in Brazil.
AB - INTRODUCTION: : The Kato-Katz technique is the standard diagnostic test for
Schistosoma mansoni infection in rural areas. However, the utility of this method
is severely limited by the day-to-day variability in host egg excretion in the
stool. In high-transmission areas, the point-of-care circulating cathodic antigen
(POC-CCA) urine assay has proven to be a reliable test. However, investigations
of the reliability of the POC-CCA assay in low-transmission regions are under
way. This study aimed to evaluate the sensitivity and specificity of the POC-CCA
assay and the morbidity of schistosomiasis in a low-endemic area in Brazil.
METHODS: : Pains City is a low-transmission zone for schistosomiasis. A total of
300 subjects aged 7-76 years were randomly selected for the POC-CCA cassette
test. For S. mansoni diagnosis, three stool samples on six slides were compared
with one urine sample for each subject. The sensitivity and specificity in the
absence of a gold standard were calculated using latent class analysis. Clinical
examinations and abdominal ultrasounds were performed in 181 volunteers to
evaluate morbidity associated with schistosomiasis. RESULTS: : The sensitivity
and specificity of the Kato-Katz technique were 25.6% and 94.6%, respectively. By
contrast, the sensitivity and specificity of the POC-CCA assay were 68.1% and
72.8%, respectively. Hepatosplenic schistosomiasis was diagnosed in two patients
(1.1%). CONCLUSIONS: : Overall, the POC-CCA urine assay proved to be a useful
test for diagnosing S. mansoni in a low-endemic area in Brazil. Severe clinical
forms of schistosomiasis can be present even in such low-endemic areas.
PMID- 28700055
TI - Biological and molecular properties of yellow venom of the Amazonian coral snake
Micrurus surinamensis.
AB - INTRODUCTION:: The coral snake Micrurus surinamensis, which is widely distributed
throughout Amazonia, has a neurotoxic venom. It is important to characterize the
biological and molecular properties of this venom in order to develop effective
antitoxins. METHODS:: Toxins from the venom of M. surinamensis were analyzed by
two-dimensional polyacrylamide gel electrophoresis and their neurotoxic effects
in vivo were evaluated. RESULTS AND CONCLUSIONS:: Most proteins in the venom had
masses < 14kDa, low phospholipase A2 activity, and no proteolytic activity. The
toxins inhibited the coagulation cascade. The venom had neurotoxic effects in
mice, with a median lethal dose upon intravenous administration of 700 ug/kg.
Immunogenic studies revealed abundant cross-reactivity of antielapidic serum with
14kDa toxins and limited cross-reactivity with toxins < 10kDa. These results
indicate that antielapidic serum against M. surinamensis venom has weak potency
(0.35mg/ml) in mice.
PMID- 28700056
TI - Injuries caused by freshwater stingrays in the Tapajos River Basin: a clinical
and sociodemographic study.
AB - INTRODUCTION: Freshwater stingray envenomations are an important cause of
morbidity in riverine populations living in various regions of Brazil. The
sequelae include temporary or permanent disability. This study aimed to identify
sociodemographic, clinical, and therapeutic aspects related to stingray injuries
in such populations. METHODS: This cross-sectional study was conducted in the
Extractive Reserve of Tapajos-Arapiuns, located in the municipalities of Santarem
and Aveiro (Para State). A convenience sample comprising 300 local adults was
used to obtain data by means of a questionnaire/ interview. RESULTS: Overall, 19
(6.3%) participants reported having sustained a stingray injury in the 12 months
prior to the study. All 19 were injured either while fishing (n=13 [68.4%]) or
engaging in other riverine activities. Most injuries [n=14 (73.7%)] occurred from
September through November, and most injured respondents [n=15 (78.9%)] reported
seeing stingrays at beaches. Severe pain and the appearance of ulcers in the
later stages of envenomation were described by 18 (94.7%) and 12 (63.2%)
participants, respectively. CONCLUSIONS: Freshwater stingray injuries, which
should be considered occupational injuries, are common in the study area,
especially in places like beaches or in the lakes that form during the dry
season, when stingrays are routinely observed. A significant proportion of
respondents was unaware of the correct first aid measures and had insufficient
resources to treat the complications of these injuries in the locality where they
reside. Interactive activities involving local residents - such as lectures and
the distribution of simple pamphlets providing information about stingray
injuries - are needed.
PMID- 28700057
TI - Neurological manifestations of dengue in Central Brazil.
AB - INTRODUCTION: : The incidence of dengue has increased throughout the 2000s with a
consequent global increase in atypical clinical forms. METHODS: : This study
reports a series of cases of neurological dengue out of 498 confirmed cases of
laboratory dengue in Goiania, Brazil. Cases were confirmed based on viral RNA
detection via polymerase chain reaction or IgM antibody capture. RESULTS: :
Neurological symptoms occurred in 5.6% of cases, including paresthesia (3.8%),
encephalitis (2%), encephalopathy (1%), seizure (0.8%), meningoencephalitis
(0.4%), and paresis (0.4%). DENV-3 was the predominant circulating serotype
(93%). CONCLUSIONS: : We reported dengue cases with neurological manifestations
in endemic area.
PMID- 28700058
TI - Spatial analysis of viral hepatitis and schistosomiasis coinfection in an endemic
area in Northeastern Brazil.
AB - INTRODUCTION:: This cross-sectional study analyzed the spatial distribution of
hepatitis B or C virus (HBV/HBC) and schistosomiasis coinfection. METHODS:: Serum
samples were collected from patients with Schistosoma mansoni infection. These
were tested for serological markers of HBV/HCV infection. The spatial
distribution of coinfection was analyzed using intensity kernel estimation.
RESULTS:: Overall, 9.4% of individuals had contact with HBV and 1.7% of samples
tested positive for anti-HCV antibodies. We identified clusters of risk located
in the central region. CONCLUSIONS:: Spatial analysis allowed visualization of
high-risk areas, leading to a definition of priority areas to be targeted for
intensification of control interventions.
PMID- 28700059
TI - First record of Anopheles konderi Galvao & Damasceno (Diptera: Culicidae)
carrying eggs of Dermatobia hominis (Linnaeus Jr.) (Diptera: Oestridae), from
Oriximina municipality, Para, Brazil.
AB - INTRODUCTION:: The muscoid fly Dermatobia hominis causes cutaneous myiases in
mammals. Females of this species use a vector to carry their eggs to the host.
This note describes Anopheles konderi acting as phoretic vector for D. hominis.
METHODS:: A female A. konderi carrying D. hominis was collected using light traps
in Oriximina, Para, Brazil. The A. konderi specimen was identified at
morphological and molecular levels. RESULTS:: Eight eggs of D. hominis were
observed on the Anopheles konderi female. CONCLUSIONS:: Anopheles konderi, only
the third Anopheles species recorded as a phoretic vector, may be a potential
vector of D. hominis.
PMID- 28700060
TI - Blackfly control from a health education perspective: the individual, the
organization, and sustainability of the process.
AB - INTRODUCTION: : This study analyzed blackfly awareness and perceptions of health
education practices for blackfly control among vulnerable populations in Brazil.
METHODS: : An exploratory descriptive quantitative research analysis was
performed to investigate and analyze the awareness of and potential participation
in blackfly control measures by vulnerable populations. RESULTS:: Countryside
resident participants (n = 24/38; 63.2% of the total sample) reported that
blackflies were an obstacle to the performance of their work activities.
CONCLUSIONS:: Blackflies are a public health problem, and actions for blackfly
control have been carried out without social participation or educational health
practices that involve proper community knowledge.
PMID- 28700061
TI - Molecular and serological characterization of Leptospira kirschneri serogroup
Pomona isolated from a human case in a Brazilian rural area.
AB - INTRODUCTION:: Leptospirosis is an important health concern in Brazil. Currently,
information on the epidemiology of the disease in the rural areas of the country
is lacking. METHODS:: Serological and molecular techniques were used to
characterize a clinical isolate of Leptospira. RESULTS:: The strain CLEP 00060,
isolated from a 59-year-old man in a rural area of Rio Grande do Sul state,
Brazil, was identified as belonging to L. kirschneri serogroup Pomona serovar
Mozdok. CONCLUSIONS:: This study contributes to the local epidemiological
knowledge of leptospirosis, prevention of the disease by vaccines, and
improvements in its diagnosis.
PMID- 28700062
TI - Seropositivity for Rickettsia spp. and Ehrlichia spp. in the human population of
Mato Grosso, Central-Western Brazil.
AB - INTRODUCTION: The epidemiology of Rickettsia and Ehrlichia species infection is
underestimated in Mato Grosso State. METHODS: : Serum samples obtained during a
Dengue outbreak in 2011-2012 were tested via indirect immunofluorescence and/or
ELISA. RESULTS: : Samples from 19/506 (3.8%) patients presented antibodies for at
least one of three Rickettsia species; 2/506 (0.4%) samples reacted against
Ehrlichia canis. Most afflicted patients are residents of cities from the south
central region of the state, where these diseases have been reported in animals.
CONCLUSIONS: : These results show serological evidence of human exposure to
Rickettsia and Ehrlichia species in Mato Grosso State.
PMID- 28700063
TI - Reassessment of quality of life domains in patients with compensated Chagas heart
failure after participating in a cardiac rehabilitation program.
AB - INTRODUCTION:: We evaluated the effects of a cardiac rehabilitation program on
quality of life. METHODS: This secondary analysis of a single-arm study included
12 patients with Chagas heart failure. The cardiac rehabilitation program
comprised exercise training and nutritional and pharmaceutical counseling.
Quality of life was assessed using the SF-36 questionnaire. RESULTS:: The program
promoted improved physical functioning (beta= +5.7; p=0.003), role-physical
(beta= +1.9; p=0.03), and bodily pain (beta= +3.5; p=0.02) scores. Moreover, the
summary physical health score (beta= +1.4; p=0.001) improved. CONCLUSION:: The
cardiac rehabilitation program significantly improved the physical quality of
life of patients with Chagas heart failure.
PMID- 28700064
TI - Clinical and epidemiological aspects of cases of tuberculosis associated with
diabetes in Salvador, Bahia, Brazil.
AB - INTRODUCTION:: This study compares the clinical and epidemiological features of
patients with TB, with and without DM. METHODS: New cases of active pulmonary TB
that occurred in Salvador, Bahia, Brazil between 2008 and 2010 were included. DM
was diagnosed by based on diagnostic criteria established by the American
Diabetes Association. RESULT: S: Of the 323 cases of TB, 44 (13.6%) were diabetic
. Patients with TB and DM were older (44.7%), with a high level of education
(34.%); had slow wound healing (23.4%) and fatigue (61.7%). CONCLUSIONS: Clinical
symptoms differed between patients with TB, with and without DM.
PMID- 28700065
TI - Encephalitis associated with the chikungunya epidemic outbreak in Brazil: report
of 2 cases with neuroimaging findings.
AB - Chikungunya, an alphavirus infection presenting with fever, rash, and
polyarthritis, is most often an acute febrile illness. Neurologic complications
of chikungunya infection have been reported. Here we report the clinical and
neuroimaging data of 2 patients with chikungunya-associated encephalitis during
the recent Brazilian epidemic.
PMID- 28700066
TI - Encephalitis associated with inappropriate antidiuretic hormone secretion due to
chikungunya infection in Recife, State of Pernambuco, Brazil.
AB - The symptoms of chikungunya virus (CHIKV) infection include fever, headache,
muscle aches, skin rash, and polyarthralgia, characterized by intense pain,
edema, and temporary functional impairment. This is the first report of
encephalitis caused by CHIKV infection associated with an atypical presentation
of syndrome of inappropriate antidiuretic hormone secretion, evolving to
cognitive impairment and apraxia of speech.
PMID- 28700067
TI - Acquired hepatocerebral degeneration in a patient with hepatitis B and hepatitis
delta virus coinfection.
AB - Acquired hepatocerebral degeneration is a neurological syndrome with typical
clinical (extrapyramidal and neuropsychiatric) symptoms and brain magnetic
resonance imaging findings (high T1 signal in the globus pallidus). It occurs
mainly in patients with advanced liver disease, such as in patients co-infected
with hepatitis B virus (HBV) and hepatitis delta virus (HDV). However, there are
no reports relating HBV/HDV coinfection and acquired hepatocerebral degeneration.
This report presents the case of a 49-year-old woman with characteristics of
acquired hepatocerebral degeneration and liver cirrhosis due to HBV/HDV
coinfection, and presents the main theories of the physiopathology of this
condition.
PMID- 28700068
TI - Implication of Tityus apiacas (Lourenco, 2002) in scorpion envenomations in the
Southern Amazon border, Brazil.
AB - Herein, four cases of scorpion stings caused by Tityus apiacas recorded from the
municipality of Apui, in the southern region of the Brazilian Amazon, are
described. Patients showed systemic clinical manifestations, described as
unusual, involuntary, and generalized tingling and numbness, reported by patients
as an electric shock sensation, lasting up to 24 hours after the sting. All
patients described local pain and sensation, along with other clinical symptoms
including local edema and erythema. Systemic manifestations were not life
threatening. Antivenom therapy was administered to all patients, who were
discharged without complaints.
PMID- 28700069
TI - Acute dengue encephalitis in a female Brazilian adult.
PMID- 28700070
TI - Granulomatous amebic encephalitis caused by Acanthamoeba sp. in an
immunocompetent Mexican adult.
PMID- 28700071
TI - Arbodiseases: a new and useful term for diseases related to arthropods.
PMID- 28700072
TI - Taxonomic status of Panstrongylus herreri Wygodzinsky, 1948 and the number of
Chagas disease vectors.
PMID- 28700073
TI - Panstrongylus herreri and its ability to develop under fluctuating environmental
conditions.
PMID- 28700074
TI - Socially Assistive Robots: Measuring Older Adults' Perceptions.
AB - To address manpower shortages, health care leaders recommend technology,
including robots, to facilitate and augment processes for delivery of efficient,
safe care. Little is known regarding older adults' perceptions of socially
assistive robots (SARs). Using the Unified Theory of Acceptance and Use
Technology framework, a survey was developed and tested for capturing older
adults' likelihood to use SARs. The Robot Acceptance Survey (RAS) comprises three
subscales: Performance Expectancy, Effort Expectancy, and Attitude. Older adults
completed the RAS pre- and post-experimental procedure with a SAR. Cronbach's
alpha coefficients for the subscales ranged from 0.77 to 0.89. Subscales were
sensitive to change, with more positive reactions after exposure to SAR
activities. Future studies must identify robotic programming capable of providing
cognitive, physical, and social assistance, as well as person-, activity-,
situation-, and robot-specific factors that will influence older adults'
acceptance of SARs. [Journal of Gerontological Nursing, 43(12), 35-43.].
PMID- 28700075
TI - South Korean Family Caregiver Involvement in Delirium Care: A Qualitative
Descriptive Study.
AB - The current study aimed to describe the effect of an educational program on RN
initiated efforts to involve family caregivers in delirium care. A descriptive
qualitative study was performed. A purposive sample of 12 RNs who participated in
a one group, pre-post evaluation of a delirium educational program, and a
nominated sample of six family caregivers of patients who had been cared for by
RNs in the program participated in individual, in-depth interviews. The
qualitative findings indicated that the inclusion of a delirium brochure in ward
orientation on admission, with reinforcement during shift changes, and RN
initiated engagement with family caregivers promoted family caregiver involvement
in delirium prevention. Further studies in South Korea are needed to determine
which family-centered nursing care interventions are culturally appropriate and
most effective for RNs and family caregivers in delirium care. [Journal of
Gerontological Nursing, 43(12), 44-51.].
PMID- 28700076
TI - Why have relative rates of class mobility become more equal among women in
Britain?
AB - In a previous paper it has been shown that across three cohorts of men and women
born in Britain in 1946, 1958 and 1970 a gender difference exists in regard to
relative rates of class mobility. For men these rates display an essential
stability but for women they become more equal. The aim of the present paper is
to shed light on the causes of this trend-or, that is, of increasing social
fluidity-among women. We begin by considering a refined version of the perverse
fluidity hypothesis: that is, one that proposes that part-time work leads to
increasing downward worklife mobility among women that also entails downward
intergenerational mobility and thus promotes greater fluidity. We do in fact find
that the increase in fluidity is very largely, if not entirely, confined to women
who have had at least one period of part-time work. However, a more direct test
of the hypothesis is not supportive. We are then led to investigate whether it is
not that part-time working itself is the crucial factor but rather that women who
subsequently work part-time already differ from those who do not at entry into
employment. We find that eventual full- and part-timers do not differ in their
class origins nor, in any systematic way, in their educational qualifications.
But there is a marked and increasing difference in the levels of employment at
which they make their labour market entry. Eventual part-timers are more likely
than eventual full-timers to enter in working-class positions, regardless of
their class origins and qualifications. Insofar as these women are from more
advantaged origins, they would appear not to seek to exploit their advantages to
the same extent as do full-timers in order to advance their own work careers. And
it is, then, in the downward mobility accepted by these women-who increase in
number across the cohorts-that we would locate the main source of the weakening
association between class origins and destinations that is revealed among women
at large.
PMID- 28700077
TI - Belonging across the lifetime: Time and self in Mass Observation accounts.
AB - Our sense of belonging rarely stands still, yet the research literature has
hitherto paid little attention to the temporal nature of belonging. Based on an
analysis of 62 Mass Observation Project (MOP) accounts written by people living
in the UK aged from their 20s to their 90s, this paper argues that as people age,
how they locate belonging in time shifts. This has to do with changing concerns
related to belonging, but also to metaphysical issues of temporality and
mortality, namely how people experience their own finite lifetime. The paper thus
offers an illustrative example of how time can be empirically researched in
sociology, with a particular focus on the important role that the future plays in
how people construct their 'functional present' (Mead ). The central argument put
forward is that time itself can be an important source of belonging, but one that
is unequally accessible to people of different ages because of contemporary
cultural scripts that present life as a linear progression into the future and
construct the future as a more meaningful temporal horizon than the past.
PMID- 28700078
TI - Are postgraduate qualifications the 'new frontier of social mobility'?
AB - We investigate the relationship between social origin, postgraduate degree
attainment, and occupational outcomes across five British age-group cohorts. We
use recently-available UK Labour Force Survey data to conduct a series of
logistic regressions of postgraduate (masters or doctorate) degree attainment
among those with first degrees, with controls for measures of degree
classification, degree subject, age, gender, ethnicity and national origin. We
find a marked strengthening of the effect of class origin on degree- and
occupational attainment across age cohorts. While for older generations there is
little or no difference by class origin in the rates at which first-degree
graduates attain postgraduate degrees, those with working-class-origins in the
youngest age-group are only about 28 per cent as likely to obtain a postgraduate
degree when compared with their peers from privileged origins. Moreover, social
origin matters more for occupational destination, even among those with
postgraduate degrees, for those in younger age groups. These findings demonstrate
the newly important, and increasing, role of postgraduate degrees in reproducing
socio-economic inequality in the wake of the substantial expansion of
undergraduate and postgraduate education. Our findings lend some support to the
Maximally Maintained Inequality thesis, suggesting that gains in equality of
access to first-degrees are indeed at risk from postgraduate expansion.
PMID- 28700079
TI - Study of the surfactant role in latex-aerogel systems by scanning transmission
electron microscopy on aqueous suspensions.
AB - For insulation applications, boards thinner than 2 cm are under design with
specific thermal conductivities lower than 15 mW m-1 K-1 . This requires binding
slightly hydrophobic aerogels which are highly nanoporous granular materials. To
reach this step and ensure insulation board durability at the building scale, it
is compulsory to design, characterise and analyse the microstructure at the
nanoscale. It is indeed necessary to understand how the solid material is formed
from a liquid suspension. This issue is addressed in this paper through wet-STEM
experiments carried out in an Environmental Scanning Electron Microscope (ESEM).
Latex-surfactant binary blends and latex-surfactant-aerogel ternary systems are
studied, with two different surfactants of very different chemical structures.
Image analysis is used to distinguish the different components and get
quantitative morphological parameters which describe the sample architecture. The
evolution of such morphological parameters during water evaporation permits a
good understanding of the role of the surfactant.
PMID- 28700080
TI - Anal HPV 16 and 18 viral load: A comparison between HIV-negative and -positive
MSM and association with persistence.
AB - Does anal HPV viral load explain the difference in anal HPV persistence between
HIV-negative and -positive men who have sex with men (MSM)? MSM >=18 years were
recruited in Amsterdam, the Netherlands, in 2010-2011. Anal self-swabs were
collected every 6 months and genotyped (SPF10 -PCR-DEIA-LIPA25 -system). HPV16
and HPV18 load was determined with a type specific quantitative (q)PCR, and
compared between HIV-negative and -positive men using ranksum test. Persistence
was defined as >=3 positive samples for the same HPV-type. Determinants of
persistent HPV16/18 infection and its association with HPV16/18 load were
assessed with logistic regression. Of 777 recruited MSM, 54 and 22 HIV negative
men were HPV16 and HPV18 positive at baseline, and 64 and 39 HIV-positive MSM.
The geometric mean titer (GMT) of HPV16 was 19.6 (95%CI 10.1-38.0) and of HPV18
8.6 (95%CI 2.7-27.5) DNA copies/human cell. HPV16 and HPV18 load did not differ
significantly between HIV-negative and -positive MSM (P = 0.7; P = 0.8,
respectively). In multivariable analyses HPV16 load was an independent
determinant of HPV16 persistence (OR 1.8, 95%CI 1.3-2.4). No difference in anal
HPV viral load was found between HIV-positive and HIV-negative MSM. HPV 16/18
viral load is an independent determinant of type-specific persistence.
PMID- 28700081
TI - Spinal nociceptive circuit analysis with recombinant adeno-associated viruses:
the impact of serotypes and promoters.
AB - Recombinant adeno-associated virus (rAAV) vector-mediated gene transfer into
genetically defined neuron subtypes has become a powerful tool to study the
neuroanatomy of neuronal circuits in the brain and to unravel their functions.
More recently, this methodology has also become popular for the analysis of
spinal cord circuits. To date, a variety of naturally occurring AAV serotypes and
genetically modified capsid variants are available but transduction efficiency in
spinal neurons, target selectivity, and the ability for retrograde tracing are
only incompletely characterized. Here, we have compared the transduction
efficiency of seven commonly used AAV serotypes after intraspinal injection. We
specifically analyzed local transduction of different types of dorsal horn
neurons, and retrograde transduction of dorsal root ganglia (DRG) neurons and of
neurons in the rostral ventromedial medulla (RVM) and the somatosensory cortex
(S1). Our results show that most of the tested rAAV vectors have similar
transduction efficiency in spinal neurons. All serotypes analyzed were also able
to transduce DRG neurons and descending RVM and S1 neurons via their spinal axon
terminals. When comparing the commonly used rAAV serotypes to the recently
developed serotype 2 capsid variant rAAV2retro, a > 20-fold increase in
transduction efficiency of descending supraspinal neurons was observed.
Conversely, transgene expression in retrogradely transduced neurons was strongly
reduced when the human synapsin 1 (hSyn1) promoter was used instead of the strong
ubiquitous hybrid cytomegalovirus enhancer/chicken beta-actin promoter (CAG) or
cytomegalovirus (CMV) promoter fragments. We conclude that the use of AAV2retro
greatly increases transduction of neurons connected to the spinal cord via their
axon terminals, while the hSyn1 promoter can be used to minimize transgene
expression in retrogradely connected neurons of the DRG or brainstem. Cover Image
for this issue: doi. 10.1111/jnc.13813.
PMID- 28700082
TI - Regulation of cotton (Gossypium hirsutum) drought responses by mitogen-activated
protein (MAP) kinase cascade-mediated phosphorylation of GhWRKY59.
AB - Drought is a key limiting factor for cotton (Gossypium spp.) production, as more
than half of the global cotton supply is grown in regions with high water
shortage. However, the underlying mechanism of the response of cotton to drought
stress remains elusive. By combining genome-wide transcriptome profiling and a
loss-of-function screen using virus-induced gene silencing, we identified
Gossypium hirsutum GhWRKY59 as an important transcription factor that regulates
the drought stress response in cotton. Biochemical and genetic analyses revealed
a drought stress-activated mitogen-activated protein (MAP) kinase cascade
consisting of GhMAP3K15-Mitogen-activated Protein Kinase Kinase 4 (GhMKK4)
Mitogen-activated Protein Kinase 6 (GhMPK6) that directly phosphorylates GhWRKY59
at residue serine 221. Interestingly, GhWRKY59 is required for dehydration
induced expression of GhMAPK3K15, constituting a positive feedback loop of
GhWRKY59-regulated MAP kinase activation in response to drought stress. Moreover,
GhWRKY59 directly binds to the W-boxes of DEHYDRATION-RESPONSIVE ELEMENT-BINDING
PROTEIN 2 (GhDREB2), which encodes a dehydration-inducible transcription factor
regulating the plant hormone abscisic acid (ABA)-independent drought response.
Our study identified a complete MAP kinase cascade that phosphorylates and
activates a key WRKY transcription factor, and elucidated a regulatory module,
consisting of GhMAP3K15-GhMKK4-GhMPK6-GhWRKY59-GhDREB2, that is involved in
controlling the cotton drought response.
PMID- 28700083
TI - Torsional resistance of XP-endo Shaper at body temperature compared with several
nickel-titanium rotary instruments.
AB - AIM: To compare the torsional resistance of XP-endo Shaper (XPS; size 30, .01
taper, FKG Dentaire, La Chaux-de-Fonds, Switzerland) instruments at body
temperature with TRUShape (TRS; size 30, .06 taper, Dentsply Tulsa Dental
Specialties, Tulsa, OK, USA), ProFile Vortex (PV; size 30, .04 taper, Dentsply
Tulsa Dental Specialties) and FlexMaster (FM; size 30, .04 taper, VDW GmbH,
Munich, Germany) nickel-titanium rotary instruments. METHODOLOGY: A metal block
with a square-shaped mould (5 mm * 5 mm * 5 mm) was positioned inside a glass
container. Five millimetres of the tip of each instrument was held inside the
metal block by filling the mould with a resin composite. The instruments were
tested for torsional resistance in saline solution at 37 degrees C. Data were
analysed using one-way analysis of variance (anova) and Tukey post hoc tests. The
significance level was set at P < 0.05. RESULTS: FM had the greatest torsional
resistance amongst the instruments tested (P < 0.001). There was no significant
difference between FM and PV instruments (P = 0.211). The ranking for torsional
resistance values was: FM > PV > TRS > XPS. CONCLUSIONS: FlexMaster and ProFile
Vortex instruments were more resistant to torsional stress compared with TRUShape
and XP-endo Shaper instruments. The manufacturing process used to produce XP-endo
Shaper instruments did not enhance their resistance to torsional stress as
compared with the other instruments.
PMID- 28700084
TI - Neural responses to social and monetary reward in early adolescence and emerging
adulthood.
AB - Reward processing is often considered to be a monolithic construct, with
different incentive types eliciting equivalent neural and behavioral responses.
The majority of the literature on reward processing has used monetary incentives
to elicit reward-related activity, yet social incentives may be particularly
important due to their powerful ability to shape behavior. Findings from studies
comparing social and monetary rewards have identified both overlapping and
distinct responses. In order to explore whether reward processing is domain
general or category specific (i.e., the same or different across reward types),
the present study recorded ERPs from early adolescents (ages 12-13) and emerging
adults (ages 18-25) while they completed social and monetary reward tasks.
Temporospatial principal components analysis revealed morphologically similar
reward positivities (RewPs) in the social and monetary reward tasks in each age
group. In early adolescents, no significant difference was found between the
magnitude of the RewP to social and monetary rewards. In emerging adults,
however, the RewP to monetary rewards was significantly larger than the RewP to
social rewards. Additionally, responses to feedback between the two tasks were
not significantly correlated in either age group. These results suggest that both
domain-general and category-specific processes underlie neural responses to
rewards and that the relative incentive value of different types of rewards may
change across development. Findings from this study have important implications
for understanding the role that neural response to rewards plays in the
development of psychopathology during adolescence.
PMID- 28700085
TI - Characterization of clinical predictors of naturally occurring NS3/NS4A protease
polymorphism in genotype 1 hepatitis C virus mono and HIV co-infected patients.
AB - Spontaneously occurring resistance may impair the success of protease inhibitors
based regimens in HCV treatment. This study aimed to evaluate associations
between amino acid substitutions in NS3/NS4A domain and clinical features of 247
HCV mono or HCV/HIV co-infected patients. Fourteen samples (5.7%) harbored at
least one resistance-associated substitution (RAS). The following RASs were
detected in NS3 region: T54S (6-2.4%), V55A (7-2.8%), and Q80R (2-0.8%). S122G
occurred in 86.9% of HCV genotype 1b samples with either natural polymorphisms or
RASs. Advanced liver fibrosis and HIV co-infection were not related to NS3/NS4A
amino acid substitutions.
PMID- 28700086
TI - Antiseptics for burns.
AB - BACKGROUND: Burn wounds cause high levels of morbidity and mortality worldwide.
People with burns are particularly vulnerable to infections; over 75% of all burn
deaths (after initial resuscitation) result from infection. Antiseptics are
topical agents that act to prevent growth of micro-organisms. A wide range are
used with the intention of preventing infection and promoting healing of burn
wounds. OBJECTIVES: To assess the effects and safety of antiseptics for the
treatment of burns in any care setting. SEARCH METHODS: In September 2016 we
searched the Cochrane Wounds Specialised Register, the Cochrane Central Register
of Controlled Trials (CENTRAL), Ovid MEDLINE, Ovid MEDLINE (In-Process & Other
Non-Indexed Citations), Ovid Embase, and EBSCO CINAHL. We also searched three
clinical trials registries and references of included studies and relevant
systematic reviews. There were no restrictions based on language, date of
publication or study setting. SELECTION CRITERIA: We included randomised
controlled trials (RCTs) that enrolled people with any burn wound and assessed
the use of a topical treatment with antiseptic properties. DATA COLLECTION AND
ANALYSIS: Two review authors independently performed study selection, risk of
bias assessment and data extraction. MAIN RESULTS: We included 56 RCTs with 5807
randomised participants. Almost all trials had poorly reported methodology,
meaning that it is unclear whether they were at high risk of bias. In many cases
the primary review outcomes, wound healing and infection, were not reported, or
were reported incompletely.Most trials enrolled people with recent burns,
described as second-degree and less than 40% of total body surface area; most
participants were adults. Antiseptic agents assessed were: silver-based, honey,
Aloe Vera, iodine-based, chlorhexidine or polyhexanide (biguanides), sodium
hypochlorite, merbromin, ethacridine lactate, cerium nitrate and Arnebia
euchroma. Most studies compared antiseptic with a topical antibiotic, primarily
silver sulfadiazine (SSD); others compared antiseptic with a non-antibacterial
treatment or another antiseptic. Most evidence was assessed as low or very low
certainty, often because of imprecision resulting from few participants, low
event rates, or both, often in single studies. Antiseptics versus topical
antibioticsCompared with the topical antibiotic, SSD, there is low certainty
evidence that, on average, there is no clear difference in the hazard of healing
(chance of healing over time), between silver-based antiseptics and SSD (HR 1.25,
95% CI 0.94 to 1.67; I2 = 0%; 3 studies; 259 participants); silver-based
antiseptics may, on average, increase the number of healing events over 21 or 28
days' follow-up (RR 1.17 95% CI 1.00 to 1.37; I2 = 45%; 5 studies; 408
participants) and may, on average, reduce mean time to healing (difference in
means -3.33 days; 95% CI -4.96 to -1.70; I2 = 87%; 10 studies; 979
participants).There is moderate certainty evidence that, on average, burns
treated with honey are probably more likely to heal over time compared with
topical antibiotics (HR 2.45, 95% CI 1.71 to 3.52; I2 = 66%; 5 studies; 140
participants).There is low certainty evidence from single trials that sodium
hypochlorite may, on average, slightly reduce mean time to healing compared with
SSD (difference in means -2.10 days, 95% CI -3.87 to -0.33, 10 participants (20
burns)) as may merbromin compared with zinc sulfadiazine (difference in means
3.48 days, 95% CI -6.85 to -0.11, 50 relevant participants). Other comparisons
with low or very low certainty evidence did not find clear differences between
groups.Most comparisons did not report data on infection. Based on the available
data we cannot be certain if antiseptic treatments increase or reduce the risk of
infection compared with topical antibiotics (very low certainty evidence).
Antiseptics versus alternative antisepticsThere may be some reduction in mean
time to healing for wounds treated with povidone iodine compared with
chlorhexidine (MD -2.21 days, 95% CI 0.34 to 4.08). Other evidence showed no
clear differences and is of low or very low certainty. Antiseptics versus non
antibacterial comparatorsWe found high certainty evidence that treating burns
with honey, on average, reduced mean times to healing in comparison with non
antibacterial treatments (difference in means -5.3 days, 95% CI -6.30 to -4.34;
I2 = 71%; 4 studies; 1156 participants) but this comparison included some
unconventional treatments such as amniotic membrane and potato peel. There is
moderate certainty evidence that honey probably also increases the likelihood of
wounds healing over time compared to unconventional anti-bacterial treatments (HR
2.86, 95% C 1.60 to 5.11; I2 = 50%; 2 studies; 154 participants).There is
moderate certainty evidence that, on average, burns treated with nanocrystalline
silver dressings probably have a slightly shorter mean time to healing than those
treated with Vaseline gauze (difference in means -3.49 days, 95% CI -4.46 to
2.52; I2 = 0%; 2 studies, 204 participants), but low certainty evidence that
there may be little or no difference in numbers of healing events at 14 days
between burns treated with silver xenograft or paraffin gauze (RR 1.13, 95% CI
0.59 to 2.16 1 study; 32 participants). Other comparisons represented low or very
low certainty evidence.It is uncertain whether infection rates in burns treated
with either silver-based antiseptics or honey differ compared with non
antimicrobial treatments (very low certainty evidence). There is probably no
difference in infection rates between an iodine-based treatment compared with
moist exposed burn ointment (moderate certainty evidence). It is also uncertain
whether infection rates differ for SSD plus cerium nitrate, compared with SSD
alone (low certainty evidence).Mortality was low where reported. Most comparisons
provided low certainty evidence that there may be little or no difference between
many treatments. There may be fewer deaths in groups treated with cerium nitrate
plus SSD compared with SSD alone (RR 0.22, 95% CI 0.05 to 0.99; I2 = 0%, 2
studies, 214 participants) (low certainty evidence). AUTHORS' CONCLUSIONS: It was
often uncertain whether antiseptics were associated with any difference in
healing, infections, or other outcomes. Where there is moderate or high certainty
evidence, decision makers need to consider the applicability of the evidence from
the comparison to their patients. Reporting was poor, to the extent that we are
not confident that most trials are free from risk of bias.
PMID- 28700087
TI - Influence of 340 mT static magnetic field on germination potential and mid
infrared spectrum of wheat.
AB - In a number of studies, a static magnetic field was observed to positively
influence the growing process of various plants; however, the effect has not yet
been related to possible structural changes. We investigate if the static
magnetic field that improves germination of wheat also alters wheat's near
infrared spectrum. Two groups of seeds were exposed to 340 mT for 16 h
cumulatively. The first group was exposed 8 days for 2 h per day, while the
second group was exposed 4 h per day for 4 consecutive days. One half of each of
the exposed seed groups as well as of the unexposed control groups was sown, and
the other half was used for mid-infrared spectra measurements. The sown seeds
were monitored for 3 weeks after sowing. Germination of the groups exposed to the
magnetic field was faster compared to corresponding non-exposed groups that were
grown under the same conditions. The magnetic field exposure caused the
enhancement of one O?H peak at 3,369 cm-1 and two C?O peaks at 1,662 cm-1 and
1,740 cm-1 in the mid-infrared spectrum. The effect was more pronounced for the 4
day, 4 h/day exposure. Bioelectromagnetics. 38:533-540, 2017.(c) 2017 Wiley
Periodicals, Inc.
PMID- 28700088
TI - Standardizing bimanual vaginal examination using cognitive task analysis.
AB - OBJECTIVE: To create a standardized universal list of procedural steps for
bimanual vaginal examination (BVE) for teaching, assessment, and simulator
development. METHODS: This observational study, conducted from June-July 2012 and
July-December 2014, collected video data of 10 expert clinicians performing BVE
in a nonclinical environment. Video data were analyzed to produce a cognitive
task analysis (CTA) of the examination steps performed. The CTA was further
refined through structured interviews to make it suitable for teaching or
assessment. It was validated through its use as a procedural examination
checklist to rate expert clinician performance. RESULTS: BVE was deconstructed
into 88 detailed steps outlining the complete examination process. These initial
88 steps were reduced to 35 by focusing on the unseen internal examination, then
further refined through interviews with five experts into 30 essential procedural
steps, five of which are additional steps if pathology is suspected. Using the
CTA as a procedural checklist, the mean number of steps performed and/or
verbalized was 21.6 +/- 3.12 (72% +/- 10.4%; range, 15.9-27.9, 53%-93%).
CONCLUSION: This approach identified 30 essential steps for performing BVE,
producing a new technique and standardized tool for teaching, assessment, and
simulator development.
PMID- 28700089
TI - Prevalence and genotype distribution of human papillomavirus among females in the
suburb of Shanghai, China.
AB - To describe the prevalence of human papillomavirus (HPV) and its genotype
distribution among females in the suburb of Shanghai. A total of 33 562
participants were enrolled in this study from January to December 2016. HPV
GenoArray test kit was used to perform HPV genotyping and was also used in DNA
amplification and HybriBio's proprietary flow-through hybridization technique.
The overall prevalence of HPV was 18.98% and the top ten genotypes of HPV
infection were HPV 16 (3.36%), HPV 58 (2.65%), HPV 52 (2.48%), HPV 51 (1.58%),
HPV 54 (1.40%), HPV 68 (1.32%), HPV 18 (1.23%), HPV 6 (1.15%), HPV 56 (1.10%),
and HPV 33 (1.07%). Single infection (4749, 14.15%) was the most common types
among all the infected cases. Significant differences were found among age groups
and month groups in terms of simple and multiple infection (P < 0.05), pure HR,
LR and mixed HPV infection (P < 0.05). The prevalence of HR and LR HPV infection
among females in the suburb of Shanghai is high, prevalence of single and
multiple infection, pure HR, LR and mixed infection is correlated with the age
and month.
PMID- 28700090
TI - Dietary practices and FODMAPs in South Asia: Applicability of the low FODMAP diet
to patients with irritable bowel syndrome.
AB - The low Fermentable Oligosaccharides, Disaccharides, and Monosaccharides And
Polyols (FODMAP) diet has been described, evaluated, and found efficacious for
the treatment of patients with irritable bowel syndrome primarily in Western
countries. The aim of this review was to address the applicability of this diet
to South Asia. The high prevalence of irritable bowel syndrome in South Asia and
its associated effects of quality of life and economics warrant the introduction
of efficacious therapies. The considerable heterogeneity of dietary patterns and
methods of food preparation across South Asian countries and a paucity of food
analysis limit precision in defining foods that are high or low in FODMAPs.
Spices and condiments are commonly consumed and mostly have a low FODMAP content.
However, major high FODMAP sources are frequently used and include onion, garlic,
shallots, legumes/pulses, and wheat-based products, as well as coconut and milk
products, offering an opportunity for dietary management to reduce the symptom
load. The feasibility of instituting a restrictive diet in which foods with a
high FODMAP content are replaced by foods low in FODMAPs must be addressed as a
substantial proportion of the nutritional intake including energy, proteins, and
micronutrients, is often obtained from FODMAP-rich food. Furthermore, limited
knowledge of health professionals together with a paucity of dietitians further
challenge the practicality of introducing the diet. Thus, while the use of the
low FODMAP diet in South Asia may be more limited than in westernized countries,
it does offer potential therapeutic opportunities, the efficacy, and impact of
which require further investigation.
PMID- 28700091
TI - Oral nonsteroidal anti-inflammatory drugs (NSAIDs) for cancer pain in adults.
AB - BACKGROUND: Pain is a common symptom with cancer, and 30% to 50% of all people
with cancer will experience moderate to severe pain that can have a major
negative impact on their quality of life. Non-opioid drugs are commonly used to
treat cancer pain, and are recommended for this purpose in the World Health
Organization (WHO) cancer pain treatment ladder, either alone or in combination
with opioids.A previous Cochrane review that examined the evidence for
nonsteroidal anti-inflammatory drugs (NSAIDs) or paracetamol, alone or combined
with opioids, for cancer pain was withdrawn in 2015 because it was out of date;
the date of the last search was 2005. This review, and another on paracetamol,
updates the evidence. OBJECTIVES: To assess the efficacy of oral NSAIDs for
cancer pain in adults, and the adverse events reported during their use in
clinical trials. SEARCH METHODS: We searched the Cochrane Central Register of
Controlled Trials (CENTRAL), MEDLINE, and Embase from inception to April 2017,
together with reference lists of retrieved papers and reviews, and two online
study registries. SELECTION CRITERIA: We included randomised, double-blind,
single-blind, or open-label studies of five days' duration or longer, comparing
any oral NSAID alone with placebo or another NSAID, or a combination of NSAID
plus opioid with the same dose of the opioid alone, for cancer pain of any pain
intensity. The minimum study size was 25 participants per treatment arm at the
initial randomisation. DATA COLLECTION AND ANALYSIS: Two review authors
independently searched for studies, extracted efficacy and adverse event data,
and examined issues of study quality and potential bias. We did not carry out any
pooled analyses. We assessed the quality of the evidence using GRADE and created
a 'Summary of findings' table. MAIN RESULTS: Eleven studies satisfied inclusion
criteria, lasting one week or longer; 949 participants with mostly moderate or
severe pain were randomised initially, but fewer completed treatment or had
results of treatment. Eight studies were double-blind, two single-blind, and one
open-label. None had a placebo only control; eight compared different NSAIDs,
three an NSAID with opioid or opioid combination, and one both. None compared an
NSAID plus opioid with the same dose of opioid alone. Most studies were at high
risk of bias for blinding, incomplete outcome data, or small size; none was
unequivocally at low risk of bias.It was not possible to compare NSAIDs as a
group with another treatment, or one NSAID with another NSAID. Results for all
NSAIDs are reported as a randomised cohort. We judged results for all outcomes as
very low-quality evidence.None of the studies reported our primary outcomes of
participants with pain reduction of at least 50%, and at least 30%, from
baseline; participants with Patient Global Impression of Change (PGIC) of much
improved or very much improved (or equivalent wording). With NSAID, initially
moderate or severe pain was reduced to no worse than mild pain after one or two
weeks in four studies (415 participants in total), with a range of estimates
between 26% and 51% in individual studies.Adverse event and withdrawal reporting
was inconsistent. Two serious adverse events were reported with NSAIDs, and 22
deaths, but these were not clearly related to any pain treatment. Common adverse
events were thirst/dry mouth (15%), loss of appetite (14%), somnolence (11%), and
dyspepsia (11%). Withdrawals were common, mostly because of lack of efficacy
(24%) or adverse events (5%). AUTHORS' CONCLUSIONS: There is no high-quality
evidence to support or refute the use of NSAIDs alone or in combination with
opioids for the three steps of the three-step WHO cancer pain ladder. There is
very low-quality evidence that some people with moderate or severe cancer pain
can obtain substantial levels of benefit within one or two weeks.
PMID- 28700092
TI - Oral paracetamol (acetaminophen) for cancer pain.
AB - BACKGROUND: Pain is a common symptom with cancer, and 30% to 50% of all people
with cancer will experience moderate to severe pain that can have a major
negative impact on their quality of life. Non-opioid drugs are commonly used to
treat mild to moderate cancer pain, and are recommended for this purpose in the
WHO cancer pain treatment ladder, either alone or in combination with opioids.A
previous Cochrane review that examined the evidence for nonsteroidal anti
inflammatory drugs (NSAIDs) or paracetamol, alone or combined with opioids, for
cancer pain was withdrawn in 2015 because it was out of date; the date of the
last search was 2005. This review, and another on NSAIDs, updates the evidence.
OBJECTIVES: To assess the efficacy of oral paracetamol (acetaminophen) for cancer
pain in adults and children, and the adverse events reported during its use in
clinical trials. SEARCH METHODS: We searched the Cochrane Central Register of
Controlled Trials (CENTRAL), MEDLINE, and Embase from inception to March 2017,
together with reference lists of retrieved papers and reviews, and two online
study registries. SELECTION CRITERIA: We included randomised, double-blind,
studies of five days' duration or longer, comparing paracetamol alone with
placebo, or paracetamol in combination with an opioid compared with the same dose
of the opioid alone, for cancer pain of any intensity. Single-blind and open
studies were also eligible for inclusion. The minimum study size was 25
participants per treatment arm at the initial randomisation. DATA COLLECTION AND
ANALYSIS: Two review authors independently searched for studies, extracted
efficacy and adverse event data, and examined issues of study quality and
potential bias. We did not carry out any pooled analyses. We assessed the quality
of the evidence using GRADE and created a 'Summary of findings' table. MAIN
RESULTS: Three studies in adults satisfied the inclusion criteria, lasting up to
one week; 122 participants were randomised initially, and 95 completed treatment.
We found no studies in children. One study was parallel-group, and two had a
cross-over design. All used paracetamol as an add-on to established treatment
with strong opioids (median daily morphine equivalent doses of 60 mg, 70 mg, and
225 mg, with some participants taking several hundred mg of oral morphine
equivalents daily). Other non-paracetamol medication included non-steroidal anti
inflammatory drugs (NSAIDs), tricyclic antidepressants, or neuroleptics. All
studies were at high risk of bias for incomplete outcome data and small size;
none was unequivocally at low risk of bias.None of the studies reported any of
our primary outcomes: participants with pain reduction of at least 50%, and at
least 30%, from baseline; participants with pain no worse than mild at the end of
the treatment period; participants with Patient Global Impression of Change
(PGIC) of much improved or very much improved (or equivalent wording). What pain
reports there were indicated no difference between paracetamol and placebo when
added to another treatment. There was no convincing evidence of paracetamol being
different from placebo with regards to quality of life, use of rescue medication,
or participant satisfaction or preference. Measures of harm (serious adverse
events, other adverse events, and withdrawal due to lack of efficacy) were
inconsistently reported and provided no clear evidence of difference.Our GRADE
assessment of evidence quality was very low for all outcomes, because studies
were at high risk of bias from several sources. AUTHORS' CONCLUSIONS: There is no
high-quality evidence to support or refute the use of paracetamol alone or in
combination with opioids for the first two steps of the three-step WHO cancer
pain ladder. It is not clear whether any additional analgesic benefit of
paracetamol could be detected in the available studies, in view of the doses of
opioids used.
PMID- 28700093
TI - Interleukin-10 release from astrocytes suppresses neuronal apoptosis via the
TLR2/NFkappaB pathway in a neonatal rat model of hypoxic-ischemic brain damage.
AB - The biological function of interleukin-10 (IL-10) and the relationship between IL
10 secretion and the Toll-like receptor 2 (TLR2) expression levels in the central
nervous system following hypoxic-ischemic brain damage (HIBD) are poorly
understood. Here, we intend to elucidate the biological function and mechanism of
IL-10 secretion following HIBD. In this study, we used a neonatal rat model of
HIBD and found that rats injected with adeno-associated virus-IL-10-shRNA (short
hairpin RNA) exhibited partially impaired learning and memory function compared
to rats administered adeno-associated virus-control-shRNA. In vitro oxygen
glucose deprivation (OGD) induced IL-10 release from astrocytes but not from
neurons. Pretreatment with exogenous recombinant IL-10 alleviated OGD-mediated
apoptosis of neurons but not astrocytes. In addition, we also observed that
hypoxic injury induced a marked increase in IL-10 expression in astrocytes as a
result of activation of the TLR2/phosphorylated nuclear factor kappa B (p
NFkappaB) p65 signaling cascade; furthermore, this effect disappeared upon small
interfering RNA targeting rat TLR2 gene (siTLR2) treatment.
Pyrrolidinedithiocarbamate, an inhibitor of NFkappaB activation, reduced the IL
10 expression levels in both OGD-injured astrocytes in vitro and the hippocampi
of HIBD rats in vivo but did not significantly affect TLR2 expression.
Furthermore, a luciferase assay revealed that p-NFkappaB p65 could bind the
1700/-1000 bp proximal region of the IL-10 gene promoter to regulate IL-10
secretion from astrocytes and that this interaction could be controlled by OGD
treatment. These data suggest that HIBD induces IL-10 secretion from astrocytes
to exert a paracrine-induced anti-apoptotic effect on injured neurons via the
TLR2/NFkappaB signaling pathway, which may improve learning and memory
dysfunction after ischemic injury.
PMID- 28700094
TI - Regulation of synaptic acetylcholine concentrations by acetylcholine transport in
rat striatal cholinergic transmission.
AB - In addition to hydrolysis by acetylcholine esterase (AChE), acetylcholine (ACh)
is also directly taken up into brain tissues. In this study, we examined whether
the uptake of ACh is involved in the regulation of synaptic ACh concentrations.
Superfusion experiments with rat striatal segments pre-incubated with [3
H]choline were performed using an ultra-mini superfusion vessel, which was
developed to minimize superfusate retention within the vessel. Hemicholinium-3
(HC-3) at concentrations less than 1 MUM, selectively inhibited the uptake of [3
H]choline by the high affinity-choline transporter 1 and had no effect on basal
and electrically evoked [3 H]efflux in superfusion experiments. In contrast, HC-3
at higher concentrations, as well as tetraethylammonium (>10 MUM), which
inhibited the uptake of both [3 H]choline and [3 H]ACh, increased basal [3
H]overflow and potentiated electrically evoked [3 H]efflux. These effects of HC-3
and tetraethylammonium were also observed under conditions where tissue AChE was
irreversibly inactivated by diisopropylfluorophosphate. Specifically, the
potentiation of evoked [3 H]efflux was significantly higher in AChE-inactivated
preparations and was attenuated by atropine. On the other hand, striatal segments
pre-incubated with [3 H]ACh failed to increase [3 H]overflow in response to
electrical stimulation. These results show that synaptic ACh concentrations are
significantly regulated by the postsynaptic uptake of ACh, as well as by AChE
hydrolysis and modulation of ACh release mediated through presynaptic muscarinic
ACh receptors. In addition, these data suggest that the recycling of ACh-derived
choline may be minor in cholinergic terminals. This study reveals a new mechanism
of cholinergic transmission in the central nervous system.
PMID- 28700095
TI - Smaller beaks for colder winters: Thermoregulation drives beak size evolution in
Australasian songbirds.
AB - Birds' beaks play a key role in foraging, and most research on their size and
shape has focused on this function. Recent findings suggest that beaks may also
be important for thermoregulation, and this may drive morphological evolution as
predicted by Allen's rule. However, the role of thermoregulation in the evolution
of beak size across species remains largely unexplored. In particular, it remains
unclear whether the need for retaining heat in the winter or dissipating heat in
the summer plays the greater role in selection for beak size. Comparative studies
are needed to evaluate the relative importance of these functions in beak size
evolution. We addressed this question in a clade of birds exhibiting wide
variation in their climatic niche: the Australasian honeyeaters and allies
(Meliphagoidea). Across 158 species, we compared species' climatic conditions
extracted from their ranges to beak size measurements in a combined spatial
phylogenetic framework. We found that winter minimum temperature was positively
correlated with beak size, while summer maximum temperature was not. This
suggests that while diet and foraging behavior may drive evolutionary changes in
beak shape, changes in beak size can also be explained by the beak's role in
thermoregulation, and winter heat retention in particular.
PMID- 28700096
TI - Peak alpha frequency is a neural marker of cognitive function across the autism
spectrum.
AB - Cognitive function varies substantially and serves as a key predictor of outcome
and response to intervention in autism spectrum disorder (ASD), yet we know
little about the neurobiological mechanisms that underlie cognitive function in
children with ASD. The dynamics of neuronal oscillations in the alpha range (6-12
Hz) are associated with cognition in typical development. Peak alpha frequency is
also highly sensitive to developmental changes in neural networks, which underlie
cognitive function, and therefore, it holds promise as a developmentally
sensitive neural marker of cognitive function in ASD. Here, we measured peak
alpha band frequency under a task-free condition in a heterogeneous sample of
children with ASD (N = 59) and age-matched typically developing (TD) children (N
= 38). At a group level, peak alpha frequency was decreased in ASD compared to TD
children. Moreover, within the ASD group, peak alpha frequency correlated
strongly with non-verbal cognition. As peak alpha frequency reflects the
integrity of neural networks, our results suggest that deviations in network
development may underlie cognitive function in individuals with ASD. By shedding
light on the neurobiological correlates of cognitive function in ASD, our
findings lay the groundwork for considering peak alpha frequency as a useful
biomarker of cognitive function within this population which, in turn, will
facilitate investigations of early markers of cognitive impairment and predictors
of outcome in high risk infants.
PMID- 28700097
TI - Crucible-Free Preparation of Transition-Metal Borides: HfB2.
AB - This study gives an account of an innovative, crucible-free technique for the
synthesis of single-phase borides at relatively moderate temperatures. A metal
wire heated by an electrical current reacts with a chosen gaseous boron halide in
a gas/solid reaction yielding a single-phase, oxygen- and carbon-free product, as
evidenced by X-ray powder diffraction and chemical analysis. This method is
demonstrated using the example of hafnium reacting with boron tribromide.
Preliminary thermodynamic considerations show that this kind of crucible-free
synthesis specifically enables the preparation of borides of transition metals
and similar elements.
PMID- 28700098
TI - Comparison of species classification models of mass spectrometry data: Kernel
Discriminant Analysis vs Random Forest; A case study of Afrormosia (Pericopsis
elata (Harms) Meeuwen).
AB - RATIONALE: The genus Pericopsis includes four tree species of which only
Pericopsis elata (Harms) Meeuwen is of commercial interest. Enforcement officers
might have difficulties discerning this CITES-listed species from some other
tropical African timber species. Therefore, we tested several methods to separate
and identify these species rapidly in order to enable customs officials to
uncover illegal trade. In this study, two classification methods using Direct
Analysis in Real Time (DARTTM) ionization coupled with Time-of-Flight Mass
Spectrometry (DART-TOFMS) data to discern between several species are presented.
METHODS: Metabolome profiles were collected using DARTTM ionization coupled with
TOFMS analysis of heartwood specimens of all four Pericopsis species and
Haplormosia monophylla (Harms) Harms, Dalbergia melanoxylon Guill. & Perr. Harms,
and Milicia excelsa (Welw.) C.C. Berg. In total, 95 specimens were analysed and
the spectra evaluated. Kernel Discriminant Analysis (KDA) and Random Forest
classification were used to discern the species. RESULTS: DART-TOFMS spectra
obtained from wood slivers and post-processing analysis using KDA and Random
Forest classification separated Pericopsis elata from the other Pericopsis taxa
and its lookalike timbers Haplormosia monophylla, Milicia excelsa, and Dalbergia
melanoxylon. Only 50 ions were needed to achieve the highest accuracy.
CONCLUSIONS: DART-TOFMS spectra of the taxa were reproducible and the results of
the chemometric analysis provided comparable accuracy. Haplormosia monophylla was
visually distinguished based on the heatmap and was excluded from further
analysis. Both classification methods, KDA and Random Forest, were capable of
distinguishing Pericopsis elata from the other Pericopsis taxa, Milicia excelsa,
and Dalbergia melanoxylon, timbers that are commonly traded.
PMID- 28700099
TI - Potential avenues for exercise to activate episodic memory-related pathways: a
narrative review.
AB - Memory function plays an important role in activities of daily living, and
consequently, quality and quantity of life. In this narrative review, we discuss
the anatomical components of episodic memory, including the structure of the
hippocampus and the routes of communication to and from this structure. We also
highlight cellular traces of memory, such as the engram cell and pathway. To
provide etiological insight, the biological mechanisms of episodic memory are
discussed, including factors subserving memory encoding (e.g., cognitive
attention, neuroelectrical indices), consolidation (i.e., synaptic and brain
systems level), and retrieval (e.g., availability of cues, context-dependent,
state-dependent, and cognitive processing). Central to this manuscript, we
highlight how exercise may influence each of these aforementioned parameters
(e.g., exercise-induced hippocampal growth, synaptic plasticity, and cue
retrieval) and then discuss the implications of these findings to enhance and
preserve memory function. Collectively, this narrative review briefly summarizes
potential mechanisms of episodic memory, and how exercise may activate these
mechanistic pathways.
PMID- 28700100
TI - Total Synthesis of (-)-N-Methylwelwitindolinone B Isothiocyanate.
AB - The asymmetric synthesis of (-)-N-methylwelwitindolinone B isothiocyanate is
reported. Critical challenges overcome through these studies include the
stereoselective installation of the sterically congested C13 alkyl chloride and
control of the wayward reactivity of the indole unit to standard oxidants. A Pt
catalyzed hydrosilylation helped stymie unwanted rearrangements facilitated by
vinyl group participation during the chloride installation step, and a new FeII
catalyzed oxidation accomplished the problematic conversion of indole into 2
indolinone.
PMID- 28700101
TI - Dynamic Equilibrium of the Aurora A Kinase Activation Loop Revealed by Single
Molecule Spectroscopy.
AB - The conformation of the activation loop (T-loop) of protein kinases underlies
enzymatic activity and influences the binding of small-molecule inhibitors. By
using single-molecule fluorescence spectroscopy, we have determined that
phosphorylated Aurora A kinase is in dynamic equilibrium between a DFG-in-like
active T-loop conformation and a DFG-out-like inactive conformation, and have
measured the rate constants of interconversion. Addition of the Aurora A
activating protein TPX2 shifts the equilibrium towards an active T-loop
conformation whereas addition of the inhibitors MLN8054 and CD532 favors an
inactive T-loop. We show that Aurora A binds TPX2 and MLN8054 simultaneously and
provide a new model for kinase conformational behavior. Our approach will enable
conformation-specific effects to be integrated into inhibitor discovery across
the kinome, and we outline some immediate consequences for structure-based drug
discovery.
PMID- 28700102
TI - Electronic messaging intervention for management of cardiovascular risk factors
in type 2 diabetes mellitus: A randomised controlled trial.
AB - AIMS AND OBJECTIVES: To determine the effectiveness of an electronic messaging
support service for management of cardiovascular risk factors in patients with
diabetes. BACKGROUND: Microletter and short message service are widely used, but
their health education benefit for people with type 2 diabetes mellitus has not
been investigated. DESIGN: Convenience sample study with randomised group
assignment. METHODS: Participants completed survey questionnaires, physical and
laboratory evaluations between May 2015 and May 2016 and were then randomly
assigned to two groups for receipt of a microletter + short message or a phone
call (control). Appointment reminders and health information were sent to the
intervention patients by microletter + short message. Every three months,
intervention patients and control patients were followed up by telephone. After
12 months, changes in cardiovascular risk factors in each group were evaluated
and compared. RESULTS: There were no statistically significant changes or between
group differences in daily smoking and drinking. There were statistically
significant between-group differences in glycated haemoglobin (p = .034),
postprandial plasma glucose (p = .001), postprandial insulin (p = .005), total
cholesterol (p = .038) and low-density lipoprotein (p < .001). Levels of glycated
haemoglobin (p = .011), fasting plasma glucose (p = .007), postprandial plasma
glucose (p < .001), fasting insulin (p = 0.004), postprandial insulin (p < .001),
total cholesterol (p < .001) and low-density lipoprotein (p < .001) were found to
be decreased significantly in intervention patients. Systolic blood pressure
decreased significantly in patients only followed by telephone (p = .014). The
microletter + short message intervention was an effective means of reducing
cardiovascular risk in patients with type 2 diabetes mellitus. CONCLUSION:
Regular smartphone communication had a favourable impact on cardiovascular risk
factors in patients with type 2 diabetes mellitus. RELEVANCE TO CLINICAL
PRACTICE: Regular smartphone communication has a favourable impact on
cardiovascular risk factors in patients with type 2 diabetes mellitus.
PMID- 28700103
TI - Copper-Assisted Amination of Boronic Acids for Synthesis of Bulky Diarylamines:
Experimental and DFT Study.
AB - Comparative investigation of copper-assisted oxidative and reductive amination
showed that the latter was preferable for the synthesis of bulky diarylamines.
DFT estimation of the mechanism of copper(I)-assisted reductive amination of
boronic acids with aryl nitroso compounds was performed and possible active
species were identified. DFT estimation of the steric penalty revealed that the
barrier for the transmetalation step for the hindered nitroso compound was almost
the same as that for the unsubstituted one, whereas a bulky group in the boronic
acid increased the activation energy. A DFT study of the influence of the
electronic properties of the substituents in both reactants on the activation
energy revealed that the optimal combination for the synthesis of unsymmetrical
diarylamines to provide better yields was an electron-rich aryl boronic acid and
an electron-deficient nitroso compound. By using these helpful guidelines, a
series of new bulky diarylamines were obtained and fully characterized.
PMID- 28700104
TI - Catalytic Intermolecular Dicarbofunctionalization of Styrenes with CO2 and
Radical Precursors.
AB - A redox-neutral intermolecular dicarbofunctionalization of styrenes with CO2 at
atmospheric pressure and carbon-centered radicals is described. This mild
protocol results in multiple C-C bond-forming reactions from simple precursors in
the absence of stoichiometric reductants, thus exploiting a previously
unrecognized opportunity that complements existing catalytic carboxylation
events.
PMID- 28700105
TI - DANTE'S INFERNO, canto XXX: Imaginary or real liver disease?
PMID- 28700106
TI - Crystallization of a Two-Dimensional Hydrogen-Bonded Molecular Assembly:
Evolution of the Local Structure Resolved by Atomic Force Microscopy.
AB - Structures of the aromatic N-heterocyclic hexaazatriphenylene (HAT) molecular
synthon obtained by surface-assisted self-assembly were analyzed with sub-A
resolution by means of noncontact atomic force microscopy (nc-AFM), both in the
kinetically trapped amorphous state and in the thermodynamically stable
crystalline phase. These results reveal how the crystallization governs the
length scale of the network order for non-flexible molecular species without
affecting the local bonding schemes. The capability of nc-AFM to accurately
resolve structural relaxations will be highly relevant for the characterization
of vitreous two-dimensional supramolecular materials.
PMID- 28700107
TI - Cigarette smoke induces rat testicular injury via mitochondrial apoptotic
pathway.
AB - An understanding of the causative mechanisms of the harmful effects of cigarette
smoke on the male reproductive system remains incomplete. Here, we investigated
three different inhaled cigarette smoke doses over five different exposure
durations to identify how the testis is affected. The effects of cigarette smoke
exposure on testicular germ cells were characterized by morphological changes and
a significant elevation in the number of apoptotic cells. Caspase 3 activation
increased dramatically after cigarette smoke exposure, accompanied by significant
time-dependent expression of the pro-apoptotic proteins Bak (B cell
lymphoma/leukemia 2 [Bcl-2] homologous antagonist killer), Bcl2l11 (a BH3 domain
only protein related to Bcl-2), Apaf1 (Apoptotic protease-activating factor-1),
and Caspase 9. Conversely, the abundance of anti-apoptotic Bcl2l2 decreased.
Taken together, our findings suggest that extensive inhalation of cigarette smoke
damages testicular germ cells through the induction of the mitochondrial
apoptotic pathway through the Bcl-2 protein family.
PMID- 28700108
TI - GPR88 in A2A receptor-expressing neurons modulates locomotor response to dopamine
agonists but not sensorimotor gating.
AB - The orphan receptor, GPR88, is emerging as a key player in the pathophysiology of
several neuropsychiatric diseases, including psychotic disorders. Knockout (KO)
mice lacking GPR88 throughout the brain exhibit many abnormalities relevant to
schizophrenia including locomotor hyperactivity, behavioural hypersensitivity to
dopaminergic psychostimulants and deficient sensorimotor gating. Here, we used
conditional knockout (cKO) mice lacking GPR88 selectively in striatal medium
spiny neurons expressing A2A receptor to determine neuronal circuits underlying
these phenotypes. We first studied locomotor responses of A2A R-Gpr88 KO mice and
their control littermates to psychotomimetic, amphetamine, and to selective D1
and D2 receptor agonists, SKF-81297 and quinpirole, respectively. To assess
sensorimotor gating performance, mice were submitted to acoustic and visual
prepulse inhibition (PPI) paradigms. Total knockout GPR88 mice were also studied
for comparison. Like total GPR88 KO mice, A2A R-Gpr88 KO mice displayed a
heightened sensitivity to locomotor stimulant effects of amphetamine and SKF
81297. They also exhibited enhanced locomotor activity to quinpirole, which
tended to suppress locomotion in control mice. By contrast, they had normal
acoustic and visual PPI, unlike total GPR88 KO mice that show impairments across
different sensory modalities. Finally, none of the genetic manipulations altered
central auditory temporal processing assessed by gap-PPI. Together, these
findings support the role of GPR88 in the pathophysiology of schizophrenia and
show that GPR88 in A2A receptor-expressing neurons modulates psychomotor
behaviour but not sensorimotor gating.
PMID- 28700109
TI - Biological responses in Balb/c mice after long-term parenteral administration of
the light subunit of mushroom tyrosinase.
AB - Light subunit of mushroom tyrosinase (LSMT) is a protein of unknown function from
mushroom Agaricus bisporus that has been demonstrated to permeate through rat
intestine ex vivo. Thus, it can be absorbed in the intestine, thereby holding a
promise as a drug carrier for oral administration, similar to HA-33 protein from
botulinum, one of the closest structural homologs of LSMT. However, the safety of
LSMT should be ensured prior to its use. Here, we described biological response
of LSMT upon weekly intraperitoneal administration of 50 MUg/day to the Balb/c
mice for 12 weeks. Motoric and behavior profiles, as well as the index of main
organs (liver, spleen, lung, heart, and kidney), and body weight, were not
significantly changed as compared with the control group. Also, no IgG was
detected in the serum. The results suggest that LSMT is safe for further
development.
PMID- 28700110
TI - Copper-Alkyne Complexation Responsible for the Nucleolar Localization of
Quadruplex Nucleic Acid Drugs Labeled by Click Reactions.
AB - G-Quadruplex(es) (G4) are noncanonical nucleic-acid structures found in guanine
rich sequences. They can be targeted with small molecules (G4 ligands) acting as
reporters, for tracking both in vitro and in cells. We explored the cellular
localization of PhenDC3 , one of the most powerful G4 ligands, by synthesizing
two clickable azide and alkyne derivatives (PhenDC3 -alk, PhenDC3 -az) and
labeling them in situ with the corresponding Cy5 click partners. A careful
comparison of the results obtained for the copper-based CuAAC and copper-free
SPAAC methodologies in fixed cells implicated CuI /alkyne intermediates in the
nonspecific localization of ligands (and fluorophores) to the nucleoli. By
contrast, SPAAC yielded similar nucleoplasmic labeling patterns in fixed and live
cells. Our findings demonstrate the need for great care when using CuAAC to
localize drugs in cells, and show that SPAAC gives results that are more
consistent between fixed and live cells.
PMID- 28700111
TI - Isotopic homogeneity throughout the skin in small cetaceans.
AB - RATIONALE: Isotope ratios from skin samples have been widely used to study
cetacean trophic ecology. Usually, isotopic skin uniformity has been assumed,
despite the heterogeneity of this tissue. This study aims to investigate (1)
regional isotopic variation within the skin in cetaceans, and (2) isotopic
variation among internal tissues. METHODS: Stable carbon (delta13 C values) and
nitrogen (delta15 N values) isotope ratios were measured in 11 skin positions in
10 common dolphins (Delphinus delphis) and 9 striped dolphins (Stenella
coeruleoalba). In addition, the isotope ratios in the muscle, liver and kidney of
both species were determined and compared with those from the skin and from all
tissues combined. The signatures were determined by means of elemental
analyser/isotope ratio mass spectrometry (EA/IRMS). RESULTS: In both species, no
differences between isotope ratios of the skin positions were found. Moreover,
the isotope ratios of skin were similar to those of muscle. In contrast, liver
and kidney showed higher isotope ratios than muscle and skin. CONCLUSIONS:
Isotopic homogeneity within the skin suggests that the isotope ratios of a sample
from a specific skin position can be considered representative of the ratios from
the entire skin tissue in dolphins. This conclusion validates the results of
previous stable isotope analyses in dolphins that used skin samples as
representative of the whole skin tissue. Isotopic similarities or dissimilarities
among tissues should be considered when analysing different tissues and comparing
results from the same or different species.
PMID- 28700112
TI - Mammalian blastocyst mimicry.
PMID- 28700113
TI - Na+ /K+ -ATPase coupled to endothelin receptor type B stimulates peripheral nerve
regeneration via lactate signalling.
AB - We have recently demonstrated that endothelin (ET) is functionally coupled to Nax
, a Na+ concentration-sensitive Na+ channel for lactate release via ET receptor
type B (ETB R) and is involved in peripheral nerve regeneration in a sciatic
nerve transection-regeneration mouse model. Nax is known to interact directly
with Na+ /K+ -ATPase, leading to lactate production in the brain. To investigate
the role of Na+ /K+ -ATPase in peripheral nerve regeneration, in this study, we
applied ouabain, a Na+ /K+ -ATPase inhibitor, to the cut site for 4 weeks with an
osmotic pump. While functional recovery and nerve reinnervation to the toe
started at 5 weeks after axotomy and were completed by 7 weeks, ouabain delayed
them by 2 weeks. The delay by ouabain was improved by lactate, and its effect was
blocked by alpha-cyano-4-hydroxy-cinnamic acid (CIN), a broad monocarboxylate
transporter (MCT) inhibitor. In primary cultures of dorsal root ganglia, neurite
outgrowth of neurons and lactate release into the culture medium was inhibited by
ouabain. Conversely, lactate enhanced the neurite outgrowth, which was blocked by
CIN, but not by AR-C155858, a MCT1/2-selective inhibitor. ET-1 and ET-3 increased
neurite outgrowth of neurons, which was attenuated by an ETB R antagonist,
ouabain and 2 protein kinase C inhibitors. Taken together with the finding that
ETB R was expressed in Schwann cells, these results demonstrate that ET enhanced
neurite outgrowth of neurons mediated by Na+ /K+ -ATPase via ETB R in Schwann
cells. This study suggests that Na+ /K+ -ATPase coupled to the ET-ETB R system
plays a critical role in peripheral nerve regeneration via lactate signalling.
PMID- 28700114
TI - Increasing incidence of melanoma after solid organ transplantation: a
retrospective epidemiological study.
AB - The risk of melanoma in organ transplant recipients (OTR) is increased compared
with the general population. This retrospective study registered all cases of
post-transplant melanoma in kidney, heart, lung, and liver transplant recipients
followed in our specialized post-transplant Dermatology Clinic since 1991. The
yearly prevalence of melanoma and skin carcinoma between 2000 and 2015 was
computed and compared in this population. Based on another cohort of kidney
transplant recipients grafted since 2005, adjusted age- and sex-standardized
incidence ratio (SIR) was calculated using a renal transplantation registry. In
our overall OTR cohort, between 1991 and 2000, five melanomas occurred in 1800
OTRs (0.28%), whereas between 1991 and 2015, 53 melanomas were diagnosed in 49 of
4510 OTR (1.09%), representing a 3.9-fold increase in prevalence after 2000.
Remarkably, the prevalence of nonmelanoma skin cancers remained unchanged over
this period. Two deaths related to melanoma were recorded with an overall follow
up of 62 months. In our cohort of 1102 renal transplant recipients, the SIR of
melanoma was 4.52. Our data suggest that contrasting with nonmelanoma skin
cancer, the risk of post-transplant melanoma has considerably increased over the
last decade.
PMID- 28700116
TI - An integrative literature review exploring the clinical management of delirium in
patients with advanced cancer.
AB - AIMS AND OBJECTIVES: To present the findings of an integrative literature review
of the evidence for the clinical management of delirium in patients with advanced
cancer. BACKGROUND: Patients with advanced cancer frequently experience delirium
which can be distressing for both patients and their families. Current guidelines
recommend that underlying causes of the delirium be addressed and a course of
antipsychotics considered. However, the research into the effectiveness of
treatments for delirium in people with advanced cancer is limited. DESIGN:
Integrative literature review. DATA SOURCES: Systematic searches of the MEDLINE,
CINAHL, ProQuest Nursing and Allied Health and PsychInfo databases were conducted
in April 2016 to include papers published in 2000 and later. The returns were
screened using inclusion and exclusion criteria, and the seven studies found to
be suitable were subject to review. REVIEW METHODS: Findings of the seven papers
were extracted, appraised critically and reviewed using a narrative approach.
RESULTS: A number of interventions, including the use of atypical antipsychotics,
opioid rotation, methylphenidate hydrochloride and coeliac plexus block, were
reported; however, there was limited evidence of their effectiveness. One study
reported the use of exercise therapy as a nonpharmacological intervention.
CONCLUSION: A variety of interventions to treat delirium in patients with
advanced cancer have been tested through nonblinded, nonrandomised trials which
have not produced a clear evidence base for practice. RELEVANCE TO CLINICAL
PRACTICE: The clinical management of delirium in patients with advanced cancer is
poorly understood and remains a clinical issue which requires further research
(particularity randomized control trials) in order to determine more effective
treatments and management strategies.
PMID- 28700115
TI - LKB1 pro-oncogenic activity triggers cell survival in circulating tumor cells.
AB - During intravasation, circulating tumor cells (CTCs) detach from the epithelium
of origin and begin the epithelial-to-mesenchymal transition (EMT) process, where
they lose epithelial features and pass through the endothelium to enter
circulation. Although detachment from the extracellular matrix is a strong source
of metabolic stress, which induces anoikis, CTCs can survive. Recently, the tumor
suppressor liver kinase B1 (LKB1) has gained attention for its role as a proto
oncogene in restoring the correct ATP/AMP ratio during metabolic stress. The aim
of this study was to assess LKB1 expression in epithelial-negative CTCs isolated
from patients with metastatic breast cancer and to characterize its possible
association with EMT and stemness features. Transcriptome analysis of EpCAM
negative CTCs indicated that over 25% of patients showed enhanced LKB1 levels,
while almost 20% of patients showed enhanced levels of an EMT transcription
factor known as ZEB1. Transcriptome and immunofluorescence analyses showed that
patients with enhanced LKB1 were correspondingly ZEB1 negative, suggesting
complementary activity for the two proteins. Only ZEB1 was significantly
associated with cancer stem cell (CSC) markers. Neither LKB1 nor ZEB1
upregulation showed a correlation with clinical outcome, while enhanced levels of
stemness-associated CD44 correlated with a lower progression-free and overall
survival. Ex vivo models showed that MDA-MB-231, a mesenchymal tumor cell line,
grew in suspension only if LKB1 was upregulated, but the MCF-7 epithelial cell
line lost its ability to generate spheroids and colonies when LKB1 was inhibited,
supporting the idea that LKB1 might be necessary for CTCs to overcome the absence
of the extracellular matrix during the early phases of intravasation. If these
preliminary results are confirmed, LKB1 will become a novel therapeutic target
for eradicating metastasis-initiating CTCs from patients with primary breast
cancer.
PMID- 28700117
TI - Infrared neural stimulation induces intracellular Ca2+ release mediated by
phospholipase C.
AB - The influence of infrared laser pulses on intracellular Ca2+ signaling was
investigated in neural cell lines with fluorescent live cell imaging. The probe
Fluo-4 was used to measure Ca2+ in HT22 mouse hippocampal neurons and
nonelectrically excitable U87 human glioblastoma cells exposed to 50 to 500 ms
infrared pulses at 1470 nm. Fluorescence recordings of Fluo-4 demonstrated that
infrared stimulation induced an instantaneous intracellular Ca2+ transient with
similar dose-response characteristics in hippocampal neurons and glioblastoma
cells (half-maximal effective energy density EC50 of around 58 J.cm-2 ). For both
type of cells, the source of the infrared-induced Ca2+ transients was found to
originate from intracellular stores and to be mediated by phospholipase C and IP3
-induced Ca2+ release from the endoplasmic reticulum. The activation of
phosphoinositide signaling by IR light is a new mechanism of interaction relevant
to infrared neural stimulation that will also be widely applicable to
nonexcitable cell types. The prospect of infrared optostimulation of the PLC/IP3
cell signaling cascade has many potential applications including the development
of optoceutical therapeutics.
PMID- 28700118
TI - Factors associated with attrition rate in a supportive care service for substance
using pregnant women in Brazil.
AB - BACKGROUND AND OBJECTIVES: Retaining substance using women in antenatal care
remains a major challenge. This study explored factors associated with attrition
rate among women with substance use problems attending a supportive care service
during pregnancy and soon after the birth of the infant. METHODS: Records of 166
women's antenatal consultations were analyzed. RESULTS: Attrition rate was high
(75/166, 45.2%), and was associated with women having no schooling/primary
schooling only, no family contact, having child(ren), crack-cocaine use, poly
drug use, and substance use problems by the expected child's father. DISCUSSION
AND CONCLUSIONS: Attrition may be the outcome of socio-demographic, family,
individual, and substance use issues not fully addressed in prenatal
interventions. SCIENTIFIC SIGNIFICANCE: Identification of who are at risk for
dropping out affords services with an opportunity to prevent its occurrence. (Am
J Addict 2017;26:676-679).
PMID- 28700119
TI - K-distribution three-dimensional mapping of biological tissues in optical
coherence tomography.
AB - Probability density function (PDF) analysis with K-distribution model of optical
coherence tomography (OCT) intensity signals has previously yielded a good
representation of the average number of scatterers in a coherence volume for
microspheres-in-water systems, and has shown initial promise for biological
tissue characterization. In this work, we extend these previous findings, based
on single point M-mode or two-dimenstional slice analysis, to full three
dimensional (3D) imaging maps of the shape parameter alpha of the K-distribution
PDF. After selecting a suitably sized 3D evaluation window, and verifying
methodology in phantoms, the resultant parametric alpha images obtained in
different animal tissues (rat liver and brain) show new contrasting ability not
seen in conventional OCT intensity images.
PMID- 28700120
TI - A 15.6 frames per second 1-megapixel multiple exposure laser speckle contrast
imaging setup.
AB - A multiple exposure laser speckle contrast imaging (MELSCI) setup for visualizing
blood perfusion was developed using a field programmable gate array (FPGA),
connected to a 1000 frames per second (fps) 1-megapixel camera sensor. Multiple
exposure time images at 1, 2, 4, 8, 16, 32 and 64 milliseconds were calculated by
cumulative summation of 64 consecutive snapshot images. The local contrast was
calculated for all exposure times using regions of 4 * 4 pixels. Averaging of
multiple contrast images from the 64-millisecond acquisition was done to improve
the signal-to-noise ratio. The results show that with an effective implementation
of the algorithm on an FPGA, contrast images at all exposure times can be
calculated in only 28 milliseconds. The algorithm was applied to data recorded
during a 5 minutes finger occlusion. Expected contrast changes were found during
occlusion and the following hyperemia in the occluded finger, while unprovoked
fingers showed constant contrast during the experiment. The developed setup is
capable of massive data processing on an FPGA that enables processing of MELSCI
data in 15.6 fps (1000/64 milliseconds). It also leads to improved frame rates,
enhanced image quality and enables the calculation of improved microcirculatory
perfusion estimates compared to single exposure time systems.
PMID- 28700121
TI - Development of a bead-based multiplexed assay for simultaneous quantification of
five bovine cytokines by flow cytometry.
AB - Quantifying cytokines is extremely important in studies of host-pathogen
interactions. Multiplex assays are commercially available but only for human and
mouse cytokines. Here a method for the simultaneous quantification of five
important bovine cytokines IFNgamma, IL-4, IL-10, IL-12, and TNFalpha in cell
culture supernatants, using flow cytometry was reported. Functional beads from BD
Biosciences expressing specific APC intensity were used. Commercially available
antibodies against bovine cytokines were covalently coupled to beads as capture
antibodies. Fixed recombinant cytokines were revealed with a second monoclonal
antibody coupled with biotin, then revealed with streptavidin-PE. This complex
was analyzed using a standard flow cytometer. Experiments were performed to check
no cross reactions had occurred. The limits of detection ranged between 0.08 and
0.4 ng/ml depending on the cytokine, and the linearity between the lower and
higher limits was remarkable (R2 > 99.8%). Finally, native cytokines from cell
culture supernatants were tested. Results were compared using the standard ELISA
test and showed that concentrations of native cytokine in cell culture
supernatants were comparable with the two methods, with a wider dynamic range
using beads and flow cytometry than with ELISA assays. Bovine IFNgamma, IL-4, IL
10, IL-12, and TNFalpha in culture supernatants can be now simultaneously
detected in a single assay, using a standard flow cytometer for both basic and
high-throughput analyses. (c) 2017 International Society for Advancement of
Cytometry.
PMID- 28700122
TI - Three-dimensional visualization system for ophthalmic microscopes using visible
light and near-infrared illumination.
AB - In this paper, we describe a three-dimensional visualization system for
ophthalmic microscopes that is aimed at microsurgery without the eyepieces. A
three-dimensional visualization system for ophthalmic microscopes using the mixed
illumination, which consists of visible light and near-infrared illumination, is
established in order to acquire more exact information of object and reduce the
amount of light irradiated to the patients, and its usage in microsurgery without
eyepieces is herein described. A custom-designed stereoscopic three-dimensional
display which is manufactured for the convenience of the surgeons during the long
time surgery, is connected directly to the camera of the ophthalmic microscope in
order to eliminate the discomfort of eyepieces to the surgeon and signal delay
between the camera, mounted on the microscope, and display device for surgeon.
The main features of the established system are the signal delay-free for surgeon
and the low level of illumination for patient. In particular, it could
significantly reduce the amount of light irradiated on a patient's eye via NIR
illumination. Upon comparison with the conventional system during clinical
ophthalmology trials, this system is confirmed to require almost the same
operation time and reduced discomfort and eyestrain during long periods of
observation.
PMID- 28700123
TI - Nonlinear Analysis to Detect if Excellent Nursing Work Environments Have Highest
Well-Being.
AB - PURPOSE: To detect potentially nonlinear associations between nurses' work
environment and nurse staffing on the one hand and nurse burnout on the other
hand. DESIGN: A cross-sectional multicountry study for which data collection
using a survey of 33,731 registered nurses in 12 European countries took place
during 2009 to 2010. METHODS: A semiparametric latent variable model that
describes both linear and potentially nonlinear associations between burnout
(Maslach Burnout Inventory: emotional exhaustion, depersonalization, personal
accomplishment) and work environment (Practice Environment Scale of the Nursing
Work Index: managerial support for nursing, doctor-nurse collegial relations,
promotion of care quality) and staffing (patient-to-nurse ratio). FINDINGS:
Similar conclusions are reached from linear and nonlinear models estimating the
association between work environment and burnout. For staffing, an increase in
the patient-to-nurse ratio is associated with an increase in emotional
exhaustion. At about 15 patients per nurse, no further increase in emotional
exhaustion is seen. CONCLUSIONS: Absence of evidence for diminishing returns of
improving work environments suggests that continuous improvement and achieving
excellence in nurse work environments pays off strongly in terms of lower nurse
reported burnout rates. Nurse staffing policy would benefit from a larger number
of studies that identify specific minimum as well as maximum thresholds at which
inputs affect nurse and patient outcomes. CLINICAL RELEVANCE: Nurse burnout is
omnipresent and has previously been shown to be related to worse patient
outcomes. Additional increments in characteristics of excellent work
environments, up to the highest possible standard, correspond to lower nurse
burnout.
PMID- 28700124
TI - Obesity reshapes stem cell extracellular vesicles.
PMID- 28700125
TI - Optical assessment of mammographic breast density by a 12-wavelength vs a
continuous-spectrum optical spectroscopy device.
AB - A 12-laser-wavelength, fixed source-detector position, cup-based optical breast
spectroscopy (OBS) device was developed for use in large-scale, multicenter
trials as a mammographic breast density (MBD) quantification and breast cancer
(BC) risk prescreening tool. In this study, the device was evaluated in
comparison with a spectrometer-based device used in previous studies. The devices
were compared on their ability to predict mammographic percent density (MPD) and
to identify women with high MBD from optical spectra. OBS measurements were made
on 60 women, (age 29-73), using both devices. Recent mammograms were collected
for all women and MPD quantified from the mammograms. Principal components (PCs)
analysis was performed on both sets of OBS spectra, and multivariate logistic
regression analysis of the resulting PC scores was used to identify women with
high MBD. Both devices are able to identify high MBD with very high sensitivity
and specificity. Partial least-squares regression of the spectra was used to
predict MPD. Both devices show a strong correlation between OBS-predicted MPD and
MPD read from mammograms, however, the correlation is stronger for the continuous
spectrum device (r = 0.74, P = .001) than for the 12-wavelength device (r = 0.62,
P = .004). Improvements to the cup-based device to reduce detector saturation
should improve the prediction of MPD from the spectra.
PMID- 28700126
TI - Contextual Factors Impacting a Pain Management Intervention.
AB - PURPOSE: To determine if findings from our preliminary study related to patient
and nursing satisfaction with a pain management intervention could be replicated
in a changed environment, and if contextual factors could impact the
effectiveness of a pain management intervention on patient satisfaction with
nursing staff's management of pain. METHODS: A prospective, experimental design
was used with six monthly assessments before, during, and after the intervention.
Data were collected from 540 patients admitted to eight medical surgical and
progressive care units and nurses that worked in these units at an academic
health sciences center in the southern United States, from March to July 2015.
The script-based, pain management communication intervention included three
specific tactics: script-based communication, use of white boards, and hourly
rounding. The Hospital Consumer Assessment of Healthcare Providers and Systems
survey was used to assess two items: "pain is well controlled" and "staff did
everything they could to help with pain." Contextual factors focused on the
practice setting. FINDINGS: Both scores for "pain is well controlled" (beta =
.028, p = 0.651) and scores for "staff did everything they could to help with
pain" (beta = .057,p = .385) did not change initially but then increased
significantly and were sustained over time. Nurses had high levels of
satisfaction with the intervention (M = 7.9, SD = 2.1) and compliance with the
intervention (M = 8.0, SD = 1.9), and had little difficulty in implementing the
intervention (M = 8.3, SD = 1.4). In terms of contextual factors, the number of
beds on the unit and the number of patients being discharged negatively impacted
scores for "pain is well controlled" and "staff did everything they could to help
with pain." Hospital length of stay positively impacted scores for "pain is well
controlled" by staff. CONCLUSIONS: Despite challenging contextual variables, the
study extended the findings of an early preliminary study in showing the
effectiveness of pain management intervention on patient satisfaction with
staff's management of pain. In evaluating the impact of an intervention, it is
essential to examine the contextual environment. CLINICAL RELEVANCE: Using
simple, clear, and consistent communication between patients and nurses related
to pain can positively impact patient satisfaction with pain management over
time. The health care environment can enhance nursing practice and patients'
outcomes.
PMID- 28700127
TI - Enhanced volumetric imaging in 2-photon microscopy via acoustic lens beam
shaping.
AB - Three-dimensional imaging at high-spatiotemporal resolutions and over large
penetration depths is key for unmasking the dynamics and structural organization
of complex biological systems. However, the need to axially shift the focus, with
consequent limitations in imaging speed, and signal degradation at large depths
due to scattering effects, makes this task challenging. Here, we present a novel
approach in 2-photon excitation microscopy that allows fast volumetric imaging
and enhanced signal-to-background (S/B) in thick tissue. Our technique is based
on ultrafast beam shaping at each pixel by means of an acoustic optofluidic lens.
Shaping the excitation beam with different phase profiles enables both high-speed
axial focus shifting, for continuous volumetric imaging, and controlled aberrated
imaging, advantageous for out-of-focus background removal. We provide a
theoretical description of our approach, and demonstrate volumetric imaging of
neuronal cells from a mouse brain slice with enhancements in S/B up to a factor
of 10 over a depth of 600 MUm.
PMID- 28700128
TI - Assessment of trans-scleral iontophoresis delivery of lutein to the human retina.
AB - The efficacy of novel scleral iontophoresis device for in situ delivery of lutein
to the human retina was assessed by Resonance Raman spectroscopy (RRS) technique.
Eight human donor eye globes were used for experiments, 6 of which underwent
trans-scleral iontophoresis delivery of lutein and the other 2 were used as
controls. The scleral iontophoresis applicator was filled with liposome-enriched
0.1% lutein solution and the generator's current was set at 2.5 mA and delivered
for 4 min. A custom RRS setup was used for detecting lutein in the inner sclera,
choroid, retinal periphery and macula of treated samples and controls. Forty
minutes after iontophoresis, the inner sclera, choroid and retinal periphery were
greatly enriched with lutein (P < .05); no lutein was found in the same ocular
regions of non-treated samples. In the same period, the average concentration of
lutein in the macula (4.8 +/- 1.7 ng/mm2 ) of treated samples was 1.3 times
greater than controls (3.7 +/- 1.0 ng/mm2 ; P = .4). Scleral iontophoresis was
shown to be effective in delivering lutein to the human retina. Future studies
will aim at assessing if this therapeutic strategy is valuable to enrich the
macular pigment in human subjects.
PMID- 28700129
TI - Shear-induced diffusion of red blood cells measured with dynamic light scattering
optical coherence tomography.
AB - Quantitative measurements of intravascular microscopic dynamics, such as absolute
blood flow velocity, shear stress and the diffusion coefficient of red blood
cells (RBCs), are fundamental in understanding the blood flow behavior within the
microcirculation, and for understanding why diffuse correlation spectroscopy
(DCS) measurements of blood flow are dominantly sensitive to the diffusive motion
of RBCs. Dynamic light scattering-optical coherence tomography (DLS-OCT) takes
the advantages of using DLS to measure particle flow and diffusion within an OCT
resolution-constrained three-dimensional volume, enabling the simultaneous
measurements of absolute RBC velocity and diffusion coefficient with high spatial
resolution. In this work, we applied DLS-OCT to measure both RBC velocity and the
shear-induced diffusion coefficient within penetrating venules of the
somatosensory cortex of anesthetized mice. Blood flow laminar profile
measurements indicate a blunted laminar flow profile and the degree of blunting
decreases with increasing vessel diameter. The measured shear-induced diffusion
coefficient was proportional to the flow shear rate with a magnitude of ~0.1 to
0.5 * 10-6 mm2 . These results provide important experimental support for the
recent theoretical explanation for why DCS is dominantly sensitive to RBC
diffusive motion.
PMID- 28700130
TI - Photostimulation effects on chicken egg development: Perspectives on human
newborn treatment.
AB - It is well known that, under exposure to bright light, eggs tend to hatch earlier
than control, without any damage to the birds. This report aims to systematically
show the effect and establishes a proposal for a possible application to
accelerate chicken egg formation, which could be extrapolated or adapted as a
great advance in premature human newborns. Comparing several protocols, the
experiments show that lower doses of light slowly delivered for 24 h promote
higher efficiency in embryo development, increasing on average 25% of its size
and more than 70% in weight when compared to the control. This weight difference
shows promising results compared to rates of up to 17% found in the literature.
These results can be a first step to reduce the stay of premature human infants
in hospitals because light, when applied in very low doses, can accelerate the
natural biological processes without risks.
PMID- 28700131
TI - High-intensity-focused ultrasound and phase-sensitive optical coherence
tomography for high resolution surface acoustic wave elastography.
AB - Elastography has the ability of quantitatively evaluating the mechanical
properties of soft tissue; thus it is helpful for diagnosis and treatment
monitoring of many diseases, for example, skin diseases. Surface acoustic waves
(SAWs) have been proven to be a non-invasive, non-destructive method for accurate
characterization of tissue elastic properties. Current SAW elastography using
high-energy laser pulse or mechanical shaker still have some problems. In order
to improve SAW elastography in medical application, a new technique was proposed
in this paper, which combines high-intensity-focused ultrasound as a SAWs impulse
inducer and phase-sensitive optical coherence tomography as a SAWs detector. A 2%
agar-agar phantom and ex-vivo porcine skin were tested. The data were processed
by a new algorithm based on the Fourier analysis. The results show that the
proposed method has the capability of quantifying the elastic properties of soft
tissue-mimicking materials. The lateral resolution of the elastogram has been
significantly improved and the different layers in heterogeneous material could
also been distinguished. Our improved technique of SAW elastography has a large
potential to be widely applied in clinical use for skin disease diagnosis and
treatment monitoring.
PMID- 28700132
TI - Non-invasive sentinel lymph node mapping and needle guidance using clinical
handheld photoacoustic imaging system in small animal.
AB - Translating photoacoustic imaging (PAI) into clinical setup is a challenge.
Handheld clinical real-time PAI systems are not common. In this work, we report
an integrated photoacoustic (PA) and clinical ultrasound imaging system by
combining light delivery with the ultrasound probe for sentinel lymph node
imaging and needle guidance in small animal. The open access clinical ultrasound
platform allows seamless integration of PAI resulting in the development of
handheld real-time PAI probe. Both methylene blue and indocyanine green were used
for mapping the sentinel lymph node using 675 and 690 nm wavelength
illuminations, respectively. Additionally, needle guidance with combined
ultrasound and PAI was demonstrated using this imaging system. Up to 1.5 cm
imaging depth was observed with a 10 Hz laser at an imaging frame rate of 5
frames per second, which is sufficient for future translation into human sentinel
lymph node imaging and needle guidance for fine needle aspiration biopsy.
PMID- 28700133
TI - A possible Fourier transform infrared-based plasma fingerprint of angiotensin
converting enzyme inhibitor-induced reversal of endothelial dysfunction in
diabetic mice.
AB - Angiotensin-converting enzyme inhibitors (ACE-I) display vasoprotective activity
and represent the cornerstone in the treatment of cardiovascular diseases. In
this study, we tested whether Fourier transform infrared (FTIR)-based analysis of
blood plasma is sensitive to detect vasoprotective effects of treatment with
perindopril including reversal of endothelial dysfunction in diabetes. For this
purpose, plasma samples were collected from untreated db/db mice, db/db mice
treated with 2 or 10 mg/kg perindopril and db+ mice. The effect of perindopril on
endothelial function was examined in ex vivo aortic rings; 10 mg/kg but not 2
mg/kg of perindopril reversed endothelial dysfunction. In plasma of db/db mice,
the balance between conformations of plasma proteins was noted, and treatment
with perindopril at a high dose but not at a low dose reversed this effect. This
was revealed by amide II/amide I ratio attributed to increased beta-sheet
formation. Spectral markers at 3010, 1520/1238 cm-1 , representative for
unsaturation degree of lipids and phosphorylation of tyrosine, respectively, were
also affected by perindopril treatment. In conclusion, although metabolic
abnormalities associated with type 2 diabetes mellitus such as
hypertriglyceridemia and hyperglycemia strongly affected spectral FTIR profile of
diabetic plasma, we identified FTIR features that seem to be associated with the
vasoprotective activity of ACE-I.
PMID- 28700134
TI - Dual fluorescence nanoconjugates for ratiometric detection of reactive oxygen
species in inflammatory cells.
AB - Reactive oxygen species (ROS) are largely produced under pathological situations.
To understand the etiology of disease, it is urgent to develop efficacious probes
for detecting ROS. Herein, a novel nanoconjugate detection system constructed
from gold clusters (AuNCs) and quantum dots (QDs) for fluorescence ratiometric
sensing ROS was reported. Upon interacting with ROS, the red emission
fluorescence (645 nm from QDs) in the detection system gradually decreased, while
the green fluorescence (480 nm from AuNCs) changed little. The fluorescence ratio
at the 2 wavelengths (I480 nm /I645 nm ) was linearly correlated with the ROS,
which could be used for the real-time ratiometric detection of ROS. The developed
nanoconjugates could be applied to monitor the ROS in inflammatory cells for its
ability of generating abundant ROS and uptaking ability to nanoparticles. The
stimulated ROS in inflammatory cells were monitored by AuNC-QD and the results
were consistent with the traditional 2', 7'-dichlorofluorescin diacetate method,
confirming the reliability of the developed method. Featured with the merits of
higher photostability, low background, high accuracy of ratiometric detection,
the AuNC-QD conjugate demonstrated its potential to be the probe for real-time
ROS detection in inflammatory cells.
PMID- 28700135
TI - A hybrid clustering algorithm for multiple-source resolving in bioluminescence
tomography.
AB - Bioluminescence tomography is a preclinical imaging modality to locate and
quantify internal bioluminescent sources from surface measurements, which
experienced rapid growth in the last 10 years. However, multiple-source resolving
remains a challenging issue in BLT. In this study, it is treated as an
unsupervised pattern recognition problem based on the reconstruction result, and
a novel hybrid clustering algorithm combining the advantages of affinity
propagation (AP) and K-means is developed to identify multiple sources
automatically. Moreover, we incorporate the clustering analysis into a general
multiple-source reconstruction framework, which can provide stable reconstruction
and accurate resolving result without providing the number of targets. Numerical
simulations and in vivo experiments on 4T1-luc2 mouse model were conducted to
assess the performance of the proposed method in multiple-source resolving. The
encouraging results demonstrate significant effectiveness and potential of our
method in preclinical BLT applications.
PMID- 28700136
TI - An automated framework to quantify areas of regional ischemia in retinal vascular
diseases with OCT angiography.
AB - In this observational and cross-sectional study, capillary nonperfusion (CNP) and
vascular changes in branch retinal vein occlusion (BRVO, sample size [n] = 26)
and choroidal neovascularization (CNV, n = 29) were evaluated. Subjects underwent
imaging using Optical coherence tomography angiography (Angiovue OCTA, RTVue XR,
Optovue Inc., Fremont, California). Local fractal analysis was applied to the
OCTA images of superficial, deep and choriocapillaris layer. CNP area (BRVO eyes)
and vascular parameters were computed using local fractal-based method.
Sensitivity and specificity of vascular parameters were assessed with receiver
operating characteristics curve. Automated CNP area showed excellent agreement
with manually quantified CNP areas in both superficial (intraclass coefficient
[ICC] = 0.96) and deep (ICC = 0.96) layers. BRVO eyes showed significantly
altered (P < .05) vascular parameters in both superficial and deep layer as
compared to normal eyes (n = 30). CNVM eyes had significantly higher capillary
free zones (P < .001) as compared to normal eyes. In normal vs BRVO eyes, vessel
density and spacing between the large vessels had similar area under the curve
(AUC) (P > .05) in both superficial (0.97 and 0.97, respectively) and deep layer
(0.99 and 0.98, respectively). Further, capillary free zones showed high AUC
(0.92) in differentiating CNV eyes from normal eyes.
PMID- 28700137
TI - Dual light-emitting diode-based multichannel microscopy for whole-slide
multiplane, multispectral and phase imaging.
AB - We report the development of a multichannel microscopy for whole-slide
multiplane, multispectral and phase imaging. We use trinocular heads to split the
beam path into 6 independent channels and employ a camera array for parallel data
acquisition, achieving a maximum data throughput of approximately 1 gigapixel per
second. To perform single-frame rapid autofocusing, we place 2 near-infrared
light-emitting diodes (LEDs) at the back focal plane of the condenser lens to
illuminate the sample from 2 different incident angles. A hot mirror is used to
direct the near-infrared light to an autofocusing camera. For multiplane whole
slide imaging (WSI), we acquire 6 different focal planes of a thick specimen
simultaneously. For multispectral WSI, we relay the 6 independent image planes to
the same focal position and simultaneously acquire information at 6 spectral
bands. For whole-slide phase imaging, we acquire images at 3 focal positions
simultaneously and use the transport-of-intensity equation to recover the phase
information. We also provide an open-source design to further increase the number
of channels from 6 to 15. The reported platform provides a simple solution for
multiplexed fluorescence imaging and multimodal WSI. Acquiring an instant focal
stack without z-scanning may also enable fast 3-dimensional dynamic tracking of
various biological samples.
PMID- 28700138
TI - Detection of protein interactions by Subcellular Localization Assay.
PMID- 28700139
TI - OCT layered tomography of the cornea provides new insights on remodeling after
photorefractive keratectomy.
AB - OCT (optical coherence tomography) of corneal layers was generated to analyze the
remodeling of the epithelium and stroma after photorefractive keratectomy (PRK).
Myopic PRK was performed in 15 patients. One eye underwent manual scraping of
epithelium while the other was treated with Epi clear. Epi clear allowed a
gentler removal of the epithelium compared to manual scraping. Scheimpflug
(Pentacam, OCULUS Optikgerate Gmbh, Wetzlar, Germany) and OCT (RTVue, Optovue
Inc., Fremont, California, USA) scans of the cornea were performed before and
after PRK (3 months). The OCT scanner and Pentacam acquired 8 and 25 radial 2-D
scans of the cornea, respectively. The results showed similar topographic changes
on the anterior corneal surface between Scheimpflug and OCT imaging. The
curvature of the underlying anterior surface of the stroma after PRK was similar
to the anterior corneal surface (air-epithelium interface), when measured with
OCT. Aberrometric changes were mostly similar between Scheimpflug and OCT.
However, Scheimpflug imaging reported greater changes in spherical aberration and
corneal higher order aberrations than OCT after PRK. This is the first study to
quantify the curvatures of the stromal layers with OCT after PRK. New insights
were gained, which could be useful for refinement of surgical ablation
algorithms, refractive procedures and detection of ectasia.
PMID- 28700140
TI - Development of a molecular bioswitch using fluorescence lifetime imaging:
Incremental activation of fluorescein diacetate.
AB - Molecular bioswitches offer an invaluable asset in the shift from systemic to
targeted treatments. Within the growing arsenal of switches are imaging probes
that functionalize only in given locations or situations. Acetate esters are a
common fluorescent example, known to activate upon interaction with esterases.
Fluorescein diacetate (FDA) is one such fluorophore used in cell viability
assays. These assays rely on the fact that the compound begins colorless and with
no fluorescent signature whatsoever, and only after internalization into cells it
is possible to detect a fluorescence signal. In this study, using fluorescence
intensity (FI) and fluorescence lifetime (FLT) imaging, FDA is shown to be
fluorescent even when unactivated. Furthermore, the FLT is shown to change with
pH. Finally, the ability to image FDA in different environments simulated by
tissue-imitating phantoms is explored. Altogether, the ability of FDA to serve as
a bioswitch when measured using FLT imaging microscopy (FLIM) is assessed. The
combination of a spectrum of FDA activation and FLIM serves as a bioswitch, where
biologically relevant stimulation can generate detectable and incremental
variations.
PMID- 28700141
TI - Zero and second-derivative synchronous fluorescence spectroscopy for the
quantification of two non-classical beta-lactams in pharmaceutical vials:
Application to stability studies.
AB - The formation of metal chelates with various ligands may lead to the production
of fluorescent chelates or enhance the fluorescence of the chelating agent. This
paper describes two sensitive, selective and computer-solved methods, namely,
zero order (SF) and second-derivative synchronous spectrofluorimetry (SDSFS) for
nano-quantitation of two carbapenems; meropenem (MP) and ertapenem (EP). The
methods are based on the chelation of MP with Tb3+ and EP with Zr4+ in buffered
organic medium at pH 4.0 to produce fluorescent chelates. In the zero order
method, the relative synchronous fluorescence intensity is measured at 327.0 nm
at Deltalambda = 70.0 and 100.0 nm for MP and EP, respectively. The second method
utilizes a second-derivative technique to enhance the method selectivity and
emphasize a stability-indicating approach. The peak amplitudes (2 D) of the
second-derivative synchronous spectra were estimated to be 333.06 and 330.06 nm
for MP and EP, respectively. The proposed synchronous spectrofluorimetric methods
were validated according to the International Conference on Harmonization (ICH)
guidelines and applied successfully for the analysis of MP and EP in pure forms,
pharmaceutical vials and in synthetic mixtures with different degradants of both
drugs. Under optimum conditions, the mole-ratio method was applied and the co
ordination ratios of MP-Tb3+ and EP-Zr4+ chelates were found to be 1:1 and 1:3.
The formation constants for the chelation complexes were evaluated using the
Benesi-Hildebrand's equation; the free energy change (DeltaG) was also
calculated. The results indicated that EP-Zr4+ was more stable than the MP-Tb3+
chelate. Moreover, the developed methods were found to be selective and
inexpensive for quantitative determination of both drugs in quality control
laboratories at nano-levels.
PMID- 28700142
TI - Developing Raman spectroscopy as a diagnostic tool for label-free antigen
detection.
AB - For several decades, a multitude of studies have documented the ability of Raman
spectroscopy (RS) to differentiate between tissue types and identify pathological
changes to tissues in a range of diseases. Furthermore, spectroscopists have
illustrated that the technique is capable of detecting disease-specific
alterations to tissue before morphological changes become apparent to the
pathologist. This study draws comparisons between the information that is
obtainable using RS alongside immunohistochemistry (IHC), since histological
examination is the current GOLD standard for diagnosing a wide range of diseases.
Here, Raman spectral maps were generated using formalin-fixed, paraffin-embedded
colonic tissue sections from healthy patients and spectral signatures from
principal components analysis (PCA) were compared with several IHC markers to
confirm the validity of their localizations. PCA loadings identified a number of
signatures that could be assigned to muscle, DNA and mucin glycoproteins and
their distributions were confirmed with antibodies raised against anti-Desmin,
anti-Ki67 and anti-MUC2, respectively. The comparison confirms that there is
excellent correlation between RS and the IHC markers used, demonstrating that the
technique is capable of detecting compositional changes in tissue in a label-free
manner, eliminating the need for antibodies.
PMID- 28700143
TI - Consequences of brain tumour resection on emotion recognition.
AB - Emotion processing impairments are common in patients undergoing brain surgery
for fronto-temporal tumour resection, with potential consequences on social
interactions. However, evidence is controversial concerning side and site of
lesions causing such deficits. This study investigates visual and auditory
emotion recognition in brain tumour patients with the aim of clarifying which
lesion sites are related to impairments in emotion processing from different
modalities. Thirty-four patients were evaluated, before and after surgery, on
facial expression and emotional prosody recognition; voxel-based lesion-symptom
mapping (VLSM) analyses were performed on patients' post-surgery MRI images.
Results showed that patients' performance decreased after surgery in both visual
and auditory modalities, but, in general, recovered 3 months after surgery. In
facial expression recognition, left brain-damaged patients showed greater post
surgery deterioration than right brain-damaged ones, whose performance
specifically decreased for sadness and fear. VLSM analysis revealed two
segregated areas in the left hemisphere accounting for post-surgery scores for
happy (fronto-temporo-insular region) and surprised (middle frontal gyrus and
inferior fronto-occipital fasciculus) facial expressions. Our findings
demonstrate that surgical removal of tumours in the fronto-temporal region
produces impairment in facial emotion recognition with an overall recovery at 3
months, suggesting a partially different representation of positive and negative
emotions in the left and right hemispheres for visually - but not auditory -
presented emotions; moreover, we show that deficits in specific expression
recognition are associated with discrete lesion locations.
PMID- 28700144
TI - In vivo full-field functional optical hemocytometer.
AB - We present an in vivo lab-free full-field functional optical hemocytometer (FFOH)
for application to the capillaries of a live biological specimen, based on the
absorption intensity fluctuation modulation (AIFM) effect. Because of the
absorption difference between the red blood cells (RBCs) and background tissue
under low-coherence light illumination, an endogenous instantaneous intensity
fluctuation is generated by the AIFM effect when RBCs discontinuously traverse
the capillary. The AIFM effect is used to highlight the RBC signal relative to
the background tissue by computing the real-time modulation depth. FFOH can
simultaneously provide a flow video, the flow velocity and the RBC count.
Ourexperimental results can potentially be applied to study the physiological
mechanisms of the blood circulation systems of near-transparent live biological
samples.
PMID- 28700145
TI - Simultaneous measurements of lymphatic vessel contraction, flow and valve
dynamics in multiple lymphangions using optical coherence tomography.
AB - Lymphatic dysfunction is involved in many diseases including lymphedema,
hypertension, autoimmune responses, graft rejection, atherosclerosis, microbial
infections, cancer and cancer metastasis. Expanding our knowledge of lymphatic
system function can lead to a better understanding of these disease processes and
improve treatment options. Here, optical coherence tomography (OCT) methods were
used to reveal intraluminal valve dynamics in 3 dimensions, and measure lymph
flow and vessel contraction simultaneously in 3 neighboring lymphangions of the
afferent collecting lymphatic vessels to the popliteal lymph node in mice. Flow
measurements were based on Doppler OCT techniques in combination with exogenous
lymph labeling by Intralipid. Through these imaging methods, it is possible to
study lymphatic function and pumping more comprehensively. These capabilities can
lead to a better understanding of the regulation and dysregulation of lymphatic
vessels in health and disease. The image depicts the dynamic measurements of
lymphatic valves, lymphatic vessels cross-sectional area and lymph velocity
simultaneously measured in vivo with optical coherence tomography.
PMID- 28700146
TI - In vivo THz imaging of human skin: Accounting for occlusion effects.
AB - In vivo terahertz (THz) imaging of human skin needs to be done in reflection
geometry due to the high attenuation of THz light by water in the skin. To aid
the measurement procedure, there is typically an imaging window onto which the
patient places the area of interest. The window enables better pulse alignment
and helps keep the patient correctly positioned during the measurement. In this
paper, we demonstrate how the occlusion caused by the skin contact with the
imaging window during the measurement affects the THz response. By studying both
rapid point measurements and imaging over an area of a human volar forearm, we
find that even 5 seconds of occlusion affects the THz response. As the occlusion
time increases, the skin surface water content increases, resulting in the
reduction of the amplitude of the reflected THz pulse, especially in the first 3
minutes. Furthermore, it was found that the refractive index of the volar forearm
increased by 10% to 15% after 20 minutes of occlusion. In this work, we examine
and propose a model for the occlusion effects due to the quartz window with a
view to compensating for its influence.
PMID- 28700147
TI - ?
PMID- 28700148
TI - [Assessment and treatment of genitourinary infections].
AB - Antibiotics are most commonly prescribed for urinary bacterial infections. The
purpose of this article is to review the most common infections of the
genitourinary tract and to guide the choice of the most appropriate treatment.
This choice depends also on the patients general state, local associated
conditions and can range from observation to an emergency hospitalisation.
Primary care physicians remain in the first line to take care of these patients
but the urologists or the infectious disease specialists can provide some help in
complex situations.
PMID- 28700149
TI - [Acute urinary retention: a mechanical or functional emergency].
AB - Acute urinary retention is one of the most frequent urologic emergencies. It
occurs mostly in elderly males that suffer from prostate enlargement. Very rare
in women, it is essentially caused by vaginal prolapse and neurologic disease.
Patients with acute urinary retention suffer from lower abdominal pain and cannot
void. Medical history is the cornerstone of diagnosis. Rarely palpable on
abdominal examination, an overfilled bladder may be revealed by dullness on supra
pubic percussion. Acute urinary retention may lead to a decrease in kidney
function, and on the long term to detrusor hypocontractility. The initial
management is bladder drainage by urethral or suprapubic catheterization. Post
obstructive diuresis and hematuria are possible complications. Subsequent
evaluation is performed by the urologist on an ambulatory basis.
PMID- 28700150
TI - [Non infectious pollakiura of women : diagnosis and treatment].
AB - Overactive bladder is a frequent condition, often underdiagnosed, which affects
deeply the quality of life of patients. The main burden linked to this syndrome
is the limitation of every day life activities and the emotional impact which can
even lead to depression.This impact on quality of life makes it a public health
problem due to the high costs which stem from its management. In this context, a
prompt and correct diagnosis, excluding all differential diagnosis, is essential
before considering treatment options.
PMID- 28700151
TI - [Common medications and prostate cancer : what is the association ?]
AB - A possible association between prostate cancer and metabolic syndrome has
recently been observed. Further, multiple experimental and epidemiologic studies
have recently reported a probable association between common medications and
prostate cancer. In this article, we summarize the results of those studies that
explore the role of aspirin, oral antidiabetic medication and statins.
PMID- 28700152
TI - [Management of genitourinary trauma].
AB - Urogenital trauma often occurs in the context of polytrauma patients. In this
article, aimed at primary care practitioners and emergency physicians, we
summarise the epidemiology and aetiology of these traumas as well as their
management. The goal is to allow primary healthcare professionals to become
acquainted with diagnostic and therapeutic strategies in genitourinary trauma
patients.
PMID- 28700153
TI - [Frequent uro-geriatric symptoms : helpful tools for general practitioners].
AB - Each developed country faces an aging population. Increase of age rises the risk
to develop urologic pathology especially in men. Routine investigation and
diagnostic of urologic pathology important, however must take into account the
patient in his globality (including age, comorbidities, drug medication as well
as sociocultural environment). The aim of this article is to help the general
practitioner in taking decisions with frequent uro-geriatric symptoms. Bladder
catheterization remains an invasive treatment and indication should be regularly
re-evaluated. Urinary infections must be distinguished from bacterial
colonisations, with some exceptions, don't need any specific treatment. We will
resume two algorithms on the management of hematuria and the management of
prostate cancer suitable for the elderly.
PMID- 28700154
TI - ?
PMID- 28700155
TI - ?
PMID- 28700156
TI - ?
PMID- 28700157
TI - ?
PMID- 28700158
TI - ?
PMID- 28700159
TI - ?
PMID- 28700160
TI - ?
PMID- 28700161
TI - ?
PMID- 28700162
TI - ?
PMID- 28700163
TI - [Direct oral anticoagulants (DOAC) : practical guidance for daily prescription].
AB - The widespread introduction of direct oral anticoagulants (DOAC) represents a
major step forward in the therapeutic management of patients with venous
thromboembolic disease and atrial fibrillation, accompanied by new challenges. A
thorough knowledge of the available evidence needs to be associated with
pragmatism in order to address patients' individual issues. Access to documents
containing practical guidance will certainly contribute to increase the efficacy
and safety of prescription of these drugs for patients. The aim of this article
is to present suggestions based on scientific data and international
recommendations for the prescription and further management of DOACs in everyday
clinical practice, based of frequently asked questions to the authors.
PMID- 28700164
TI - [The evolution of imaging techniques for the diagnosis of pulmonary].
AB - Modern diagnostic strategies for pulmonary embolism (PE) rely on the sequential
use of clinical probability assessment, D-dimer and thoracic imaging when
necessary. Computed tomography pulmonary angiography (CTPA) has become the
imaging modality of choice. Diagnostic strategies using CTPA are very safe for
the diagnosis of PE and have been well validated in large prospective management
outcome studies. With the widespread use of CTPA, concerns regarding radiation
and overdiagnosis of PE have paved the way for investigating new diagnostic
modalities. V/Q SPECT has arisen as a highly accurate test and a potential
alternative to CTPA. However, prospective management outcome studies are still
lacking and are warranted before its implementation in routine clinical practice.
PMID- 28700165
TI - [Complications and management of percutaneous femoral arterial access].
AB - Vascular access complications following endovascular procedures remain an
important cause of morbidity when using a femoral approach. In this review, we
describe the risk factors, clinical presentation and management of hematoma,
retroperitoneal bleeding, pseudoaneurysms, arteriovenous fistulae and arterial
thrombosis.
PMID- 28700166
TI - [Foam sclerotherapy to treat varicose veins].
AB - The ultrasound-guided foam sclerotherapy (UGFS) involves the injection of a
sclerosing agent into a target vein under ultrasonographic guidance. The goal of
this treatment is to harm the venous endothelium to achieve the destruction of
the vein wall by a fibrosis phenomenon. In this article, we discuss indications
and contraindications of UGFS. We also describe the technique, its efficacy and
its complications.
PMID- 28700167
TI - [Relevance of contrast ultrasound with microbubbles in vascular medecine].
AB - Application of ultrasound contrast media has become a standard in diagnostic
imaging in cardiology and in the characterization of focal lesions in multiple
organs, especially of the liver. In the past years there was a growing body of
evidence for their usefulness in vascular medicine. The development of contrast
media, microbubbles with a stabilizing envelope and filled with gaz, small enough
to pass through pulmonary capillaries made real-time imaging of organ perfusion
possible. Ultrasound contrast media are rapidly eliminated by exhalation and can
safely be administered to patients with renal failure. The objective of this
review is to describe the basic principles of ultrasound contrast imaging and to
inform about vascular applications of contrast ultrasound.
PMID- 28700169
TI - ?
PMID- 28700168
TI - ?
PMID- 28700170
TI - ?
PMID- 28700171
TI - ?
PMID- 28700172
TI - ?
PMID- 28700173
TI - ?
PMID- 28700174
TI - ?
PMID- 28700175
TI - ?
PMID- 28700176
TI - ?
PMID- 28700177
TI - [Editorial].
PMID- 28700178
TI - [Nephrology in Emilia Romagna Region].
PMID- 28700179
TI - [Clinical manifestations and therapeutic perspectives in tuberous sclerosis, a
rare multi-organ genetic disease with renal involvement].
AB - Tuberous sclerosis is a rare genetic disease with multiple organ involvement.
Renal involvement is manifested by the presence of angiomyolipomas and cysts.
Angiomyolipomas due to the progressive increase in size over time can complicate
by bleeding that can lead to severe retroperitoneal hemorrhages. Hence, it is
important to perform an active surveillance of the masses and to institute
therapeutic attempts in order to manage or prevent any complication. We present
three clinical cases of three women with various clinical presentations and
treated in different ways. Recently, the employment of mTOR inhibitors such as
Everolimus has been shown therapeutic efficacy in this disease, especially in
terms of a dimensional reduction of renal angiomyolipomas.
PMID- 28700180
TI - [Superior Cava Vein stenosis in a hemodialysis patient with long-term central
venous catheter and vascular graft: a case report].
AB - Recently, the use of central venous catheters (CVC) as a vascular access in
patients undergoing hemodialysis is significantly increased, mainly because of
the aging of this population and the presence of several comorbidities. However,
the implantation and the long stay of CVC are associated with many complications.
Among them, central venous stenosis represents one of the most common problems
that, if not properly diagnosed, could lead to vascular thrombosis and consequent
vascular access malfunction. Here, we report a case of a 38-year-old patient, who
underwent hemodialysis firstly by a CVC long-term into right jugular vein and
then by a prosthetic fistula in the ipsilateral limb. The patient presented many
episodes of vascular access thrombosis that required endovascular interventions.
The ultrasound screening and CT-angiography revealed an asymptomatic stenosis of
the superior cava vein, which treatment with the implantation of vascular stent
resulted in an initial improvement of vascular access performance. However, in
the following months, a restenosis was observed that required new interventions
to reestablish a satisfactory vascular access function. This case highlights that
patients on hemodialysis should undergo proper clinical and instrumental follow
up in order to prevent or early recognize vascular access complications.
PMID- 28700181
TI - [Hyperuricemia and gene mutations: a case report].
AB - Hyperuricemia is frequently found in nephrology. The case presented may be useful
to clarify some pathogenetic aspects. It is a patient of 18 years,
hyperuricaemic. Non-consanguineous parents, hyperuricemia in the paternal line,
not neuropsychiatric disorders in the family. Delay in neuromotor acquisitions,
average intellectual disabilities, anxiety disorder, obsessive-compulsive
personality traits. Normal renal function and renal ultrasound. Evidence of
hyperuricemia in 2015. Never gouty episodes and / or lithiasis, initiated
allopurinol 100 mg on alternate days, with no side effects, urea in the control
range, slightly below normal uricuria. Given the complex clinical, he carried out
a genetic analysis of array-CGH. He showed a deletion on the short arm of
chromosome 3 (3p12.3) and a duplication of the long arm of chromosome 1 (19q13
42). The deletion 3p12.3 (paternal inheritance), involves the ROBO2 gene.
Duplication 19q13.42, (maternal inheritance), includes NLRP12, DPRX, ZNF331
genes. The ROBO2 gene with its mutation, is associated with vesicoureteral
reflux. The NLRP12 gene encodes proteins called "Nalps", forming a subfamily of
proteins "CATERPILLAR". Many "Nalps" as well as the "Nalps 12" have an N-terminal
domain (DYP) with a purin. Since uric acid is a byproduct of purine metabolism,
considered the familiarity, we believe that we can hypothesize that the mutations
found. In particular those concerning the NLRP-12 gene, may have a role in the
presence of hyperuricemia. We believe that in patients with hyperuricemia,
associated with a particular impairment of neurological picture, it is likely
that there is a subtended common genetic deficiency.
PMID- 28700182
TI - [Brachial artery pseudoaneurysm: a rare but serious complication in hemodialysis
patients with arteriovenous fistula].
AB - A pseudoaneurysm or false aneurysm of the brachial artery is an uncommon
occurrence in patients receiving hemodialysis with arteriovenous fistula (AVF).
We describe the case of a 76-year-old woman presenting with a large, tender,
pulsatile mass in the right antecubital region 10 cm from the AVF. B-mode
ultrasound examination revealed a saccular hematoma. Color doppler showed a
recirculation movement of blood, creating a two colors image called "Korean
flag". The patient was transferred to the surgical unit where she first underwent
ultrasound-guided compression and then surgical repair of the pseudoaneurysm. Two
weeks after surgery the AVF was used again as an access for hemodialysis.
Differentiating between a false and a true aneurysm based on ultrasound is not
always straightforward. Doppler ultrasound findings can be decisive for the early
diagnosis of a pseudoaneurysm to ensure proper treatment planning given the
dangerous complications of ruptures. Treatment options include: compression,
percutaneous thrombin injection, endovascular exclusion with covered stents,
aneurysmectomy and surgical repair.
PMID- 28700183
TI - Taste disorders in patients with end-stage chronic kidney disease.
AB - The authors aimed to explore taste distortion in patients with chronic kidney
disease (CKD). One hundred and four patients were divided into a control group
and a study group. The data was collected through a questionnaire and was
statistically analyzed. The results showed that 28.7% of respondents had a loss
of taste (96.60% CKD patients). There was a statistically significant correlation
between the duration of treatment and taste loss, between patients' age and taste
impairment, and between patients' age and the sense of a metallic taste in the
mouth. Distortion in the sense of taste is an oral manifestation characteristic
of CKD patients.
PMID- 28700184
TI - [Report for the World Kidney Days in Italy 2015-2016].
AB - World Kidney Day (WKD) is a global campaign, promoted by International Federation
of Kidney Foundations (IFKF) and International Society of Nephrology (ISN) aimed
at raising awareness among people on importance of our kidneys. This campaign
includes many events across the globe. The main purpose of WKD is to create and
spread awareness about preventive behaviours and risk factors for renal diseases.
In Italy WKD is organized by the Italian Kidney Foundation (FIR) in collaboration
with Italian Society of Nephrology (SIN) and the Red Cross of Italy. It takes
place in hospitals, public spaces and in schools, where each participant is
provided with informative material together with blood pressure and urine
dipstick testing. Here, we present the data collected during the 2015 and 2016
WKD campaigns.
PMID- 28700185
TI - [Dialysis and cookers: a project for the empowerment of patients in managing
their own chronic renal failure].
AB - The phosphate and potassium control is indispensable to dominate the secondary
hyperparathyroidism and reduce cardiovascular mortality in dialysis patients.
Most of them receive only theoretical nutritional information. We therefore
organized a cooking workshop for dialysis patients, with a multidisciplinary team
consisting of nurses, nephrologists, a dietitian and a professional chef, to
directly teach the patients and their families how to realize a low phosphorus
and potassium menu, assessing the proper use of phosphate binders, and blood
tests at baseline and at three and six months. Twenty-four patients, out of 133,
attended the workshop with a family member, filling out a questionnaire on eating
habits, knowledge about phosphorus and potassium, and about binders. Theoretical
and practical information about phosphorus and potassium metabolism, about
binders, and cooking techniques were given during the evening, we then prepared a
meal, eaten all together. The questionnaire was repeated at the end of the
evening, and all the participants reported an improvement of the considered
variables. Phosphorus and potassium plasma levels and the number of binders did
not change after three and six months. Coping with the dietary changes related to
the start of the dialytic therapy in an informal atmosphere, with a family
member, is highly appreciated, clinically useful, logistically and economically
sustainable. A customized and long-lasting counselling is probably required to
modify plasma levels of phosphorus and potassium and binder's consumption. The
poor dietary knowledge detected in our patients and the satisfaction about the
course both confirm the training needs in this area.
PMID- 28700186
TI - [The treatment of AKI in nephrology hospitalization: the SLE-HDF 15 litres in 10
hours].
AB - The AKI in intensive care has been widely treated by international and national
guidelines. The treatment of AKI in patients not requiring admission in Intensive
Care Unit, but often hospitalized in Nephrology Unit, it is showed of less
relevance. For over 5 years we have used for the treatment of AKI of patients
admitted in Nephrology Unit an intermittent slow technique, implemented in
approximately 600 patients with AKI for a total of about 3000 treatments. In this
study we report the clinical results obtained in 100 consecutive patients
referred to our Nephrology Unit from 1st January 2014. We excluded the patients
with AKI and lactic acidosis by metformin, which were treated with CVVHDF. The
Dialysis Protocol provides a slow low efficiency intermittent treatment called
SLE-HDF (Sustained Low Efficiency Hemo-Dia-Filtration), with 10-hour duration,
1.5 L/h dialysate for a patient up to 75 kg, 2 L/h up to 85 kg, 2.5 L/h over 85
kg. Half of the dialysate was used in convention in post and half in diffusion.
Endpoints were the recovery of renal function and the survival of the patient. On
each patient was calculated on at least one seat, the Kt/V urea (UKt/V). Were
studied 100 patients, 45 females and 55 males, with mean age 79.4 + 11 years. The
weight was 74 kg + 18 kg at the start of treatment. The 65% of patients had
diuresis < to 500 ml/24 hours. The causes of AKI were: 41% heart failure, 31 %
AKI on MRC, 7% rhabdomyolysis, 6% Hepato-renal Syndrome, 4% sepsis, 11 % other
causes. Major comorbidities were heart disease (63%), diabetes (50%), COPD (38%),
age over 85 years, cancers 23, liver disease 16, hypotension requiring amine 15,
sepsis 10. In total in the 100 patients, 512 treatments were performed, average
5.12 + 3.7. The mean UKt/V was 0.4 + 0.05 per session. The deaths were 43.
Patients discharged were 57. Of these, 43 had a recovery of renal function.
Fourteen patients have not recovered renal function and were admitted for chronic
dialysis treatment. In conclusion, our protocol of SLE-HDF, which uses volumes of
dialysate sharply lower than used in literature, has been shown to be effective
in correcting the biochemical profile of the patient with AKI. The clinical
results are considered satisfactory, having obtained the improvement in 57% of
patients, considering that the 43 deaths, 10 were suffering from Hepato-cirrhosis
and 13 from malignant neoplasm. Further studies are needed to confirm our
findings.
PMID- 28700187
TI - [Safety Regulations in the Healthcare Workplaces].
AB - The law n. 81/2008 gathers the regulations about the health safeguard and safety
in the workplaces. It provides the duty of risk management, the designation of a
responsible for the prevention and protection services, the designation of a
specialist doctor for the surveillance of the operators and of the workplaces and
a training focused on safety for all the operators. In the healthcare workplaces
usually we can distinguish between the risks for the workers safety and the risks
for the workers health. The art.43 of the law 81/2008 also provides the legal
guarantee both for other people attending workplaces and patients. In fact the
law n.24/2017 at the art. 1 confirms that the care safety is part of the health
right.
PMID- 28700188
TI - [Limit landscapes in the era of technicality].
AB - In the era of technicality, man seems to have lost the sense and true dimension
of the limit: it has thus become something to be annihilated and a point that
needs to move further and further not only for human curiosity but also because
of profit economic development that governs globalized progress. In this
scenario, the Author reflects on the most authentic sense of the limit and tries
to defend it because our gender identity is bound to be limited.
PMID- 28700190
TI - Getting to the Root of High Prescription Drug Prices.
AB - ISSUE: Historic increases in prescription drug prices and spending are
contributing to unsustainable health care costs in the United States. There is
widespread public support for elected officials to address the problem. GOAL: To
document the drivers of high U.S. prescription drug prices and offer a broad
range of feasible policy actions. METHODS: Interviews with experts and
organizations engaged with prescription drug development and utilization,
pricing, regulation, and clinical practice. Review of policy documents,
proposals, and position statements from a variety of stakeholders. FINDINGS AND
CONCLUSIONS: Congress and regulators can undertake a wide range of policy actions
to begin to rebalance incentives for innovation and price competition, prioritize
patient access and affordability, and maximize the availability of information to
patients, providers, and payers.
PMID- 28700191
TI - Assistance to States for the Education of Children With Disabilities and
Preschool Grants for Children With Disabilities Program; Early Intervention
Program for Infants and Toddlers With Disabilities. Final regulations.
AB - The Secretary of Education (Secretary) amends the regulations implementing Parts
B and C of the Individuals with Disabilities Education Act (IDEA). These
conforming changes are needed to implement statutory amendments made to the IDEA
by the Every Student Succeeds Act (ESSA), enacted on December 10, 2015. These
regulations remove and revise IDEA definitions based on changes made to the
definitions in the Elementary and Secondary Education Act of 1965 (ESEA), as
amended by the ESSA, and also update several State eligibility requirements to
reflect amendments to the IDEA made by the ESSA. They also update relevant cross
references in the IDEA regulations to sections of the ESEA to reflect changes
made by the ESSA. These regulations also include several technical corrections to
previously published IDEA Part B regulations.
PMID- 28700193
TI - Medicaid/CHIP Program; Medicaid Program and Children's Health Insurance Program
(CHIP); Changes to the Medicaid Eligibility Quality Control and Payment Error
Rate Measurement Programs in Response to the Affordable Care Act. Final rule.
AB - This final rule updates the Medicaid Eligibility Quality Control (MEQC) and
Payment Error Rate Measurement (PERM) programs based on the changes to Medicaid
and the Children's Health Insurance Program (CHIP) eligibility under the Patient
Protection and Affordable Care Act. This rule also implements various other
improvements to the PERM program.
PMID- 28700194
TI - California Public Hospitals Improved Quality of Care Under Medicaid Waiver
Program.
AB - California has 12 county-owned and operated hospital systems and 5 University of
California hospitals designated as public hospitals. These organizations deliver
the majority of inpatient care and a significant amount of outpatient care to
Medicaid patients in the state. In 2010, California was the first state in the
nation to implement a five-year Delivery System Reform Incentive Payment (DSRIP)
program under the Section S1115 Medicaid "Bridge to Reform" waiver to improve the
capacity of these hospitals to deliver high quality and more efficient care. The
California DSRIP was the first program in a continuing national initiative to
reform the Medicaid delivery system while remaining budget neutral. An extensive
evaluation revealed major advances in infrastructure development, delivery of
health care, and patient outcomes during the program. The results highlight the
importance of joint federal and state investments in bolstering the capacity of
safety net providers to deliver high-quality care, and they emphasize the need
for continued investment in the safety net. The California DSRIP was followed by
a program called Public Hospital Redesign and Incentives in Medi-Cal (PRIME),
which incentivizes improvements in expanded and new areas of care not addressed
by DSRIP
PMID- 28700202
TI - Solution-Processable High-Quality Graphene for Organic Solar Cells.
AB - The unique optical and electronic properties of graphene open up new
opportunities for optoelectronics. This work reports the use of solution
processed high-quality graphene as transparent conductive electrode in an organic
solar cell using an electrochemical approach. The fabricated thieno[3,4
b]thiophene/benzodithiophene:phenyl-C71-butyric acid methyl ester (PTB7:PCB71M)
bulk heterojunction organic solar cell based on the exfoliated graphene (EG)
anode exhibits a power conversion efficiency of 4.23%, making EG promising for
next-generation flexible optoelectronic devices.
PMID- 28700203
TI - Mechanisms of Atmospherically Relevant Cluster Growth.
AB - Atmospheric aerosols impact global climate either directly by scattering solar
radiation or indirectly by serving as cloud condensation nuclei, which influence
cloud albedo and precipitation patterns. Our scientific understanding of these
impacts is poor relative to that of, for instance, greenhouse gases, in part
because it is difficult to predict particle number concentrations. One important
pathway by which particles are added to the atmosphere is new particle formation,
where gas phase precursors form molecular clusters that subsequently grow to the
climatically relevant size range (50-100 nm diameter). It is predicted that up to
50% of atmospheric particles arise from this process, but the key initial
chemical processes are poorly resolved. In general, a combination of inorganic
and organic molecules are thought to contribute to new particle formation, but
the chemical composition of molecular clusters and pathways by which they grow to
larger sizes is unclear. Cluster growth is a key component of new particle
formation, as it governs whether molecular clusters will become climatically
relevant. This Account discusses our recent work to understand the mechanisms
underlying new particle growth. Atmospherically relevant molecular clusters
containing the likely key contributors to new particle formation (sulfuric acid,
ammonia, amines, and water) were investigated experimentally by Fourier transform
mass spectrometry as well as computationally by density functional theory. Our
laboratory experiments investigated the molecular composition of charged
clusters, the molecular pathways by which these clusters may grow, and the
kinetics of base incorporation into them. Computational chemistry allowed
confirmation and rationalization of the experimental results for charged clusters
and extension of these principles to uncharged and hydrated clusters that are
difficult to study by mass spectrometry. This combination of approaches enabled
us to establish a framework for cluster growth involving sulfuric acid, ammonia,
amines, and water. Charged or uncharged, cluster growth occurs primarily through
an ammonium (or aminium) bisulfate coordinate. In these clusters, proton transfer
is maximized between acids and bases to produce cations (ammonium, aminium) and
anions (bisulfate), whereas additional molecules (water and unneutralized
sulfuric acid) remain un-ionized. Experimental measurements suggest the growth of
positively charged clusters occurs by successive acidification and neutralization
steps. The acidification step is nearly barrierless, whereas the neutralization
step exhibits a significant activation barrier in the case of ammonia. Bases are
also incorporated into these clusters by displacement of one base for another.
Base displacement is barrierless on the cluster surface but not within the
cluster core. The favorability of amines relative to ammonia in charged clusters
is governed by the trade-off between gas phase basicity and binding energetics.
Computational studies indicate that water has a relatively small effect on
cluster energetics. In short, amines are effective at assisting the formation and
initial growth of clusters but become less important as cluster size increases,
especially when hydration is considered. More generally, this work shows how
experiment and computation can provide important, complementary information to
address problems of environmental interest.
PMID- 28700204
TI - Effect of Terminal-Group Functionality on the Ability of Dendrimers to Bind
Proteins.
AB - It is known that dendrimers can bind proteins with good selectively. This
selectivity comes about from an optimization based on matching the size of the
dendrimer with the size of the protein's interfacial binding area. In this paper,
we report how this selectivity can be moderated by the functionality on the
surface of the dendrimer. Specifically, we describe the synthesis of amino acid
functionalized dendrimers and the effect of functionality on the dendrimer's
ability to bind and inhibit the enzymatic protein, chymotrypsin. The results show
how dendrimer binding can be increased or decreased depending on the terminal
functionality. These results will allow new ligands to be designed and
synthesized, possessing increased and selective protein-binding abilities.
PMID- 28700205
TI - Flexible and Robust Thermoelectric Generators Based on All-Carbon Nanotube Yarn
without Metal Electrodes.
AB - As practical interest in flexible/or wearable power-conversion devices increases,
the demand for high-performance alternatives to thermoelectric (TE) generators
based on brittle inorganic materials is growing. Herein, we propose a flexible
and ultralight TE generator (TEG) based on carbon nanotube yarn (CNTY) with
excellent TE performance. The as-prepared CNTY shows a superior electrical
conductivity of 3147 S/cm due to increased longitudinal carrier mobility derived
from a highly aligned structure. Our TEG is innovative in that the CNTY acts as
multifunctions in the same device. The CNTY is alternatively doped into n- and p
types using polyethylenimine and FeCl3, respectively. The highly conductive CNTY
between the doped regions is used as electrodes to minimize the circuit
resistance, thereby forming an all-carbon TEG without additional metal
deposition. A flexible TEG based on 60 pairs of n- and p-doped CNTY shows the
maximum power density of 10.85 and 697 MUW/g at temperature differences of 5 and
40 K, respectively, which are the highest values among reported TEGs based on
flexible materials. We believe that the strategy proposed here to improve the
power density of flexible TEG by introducing highly aligned CNTY and designing a
device without metal electrodes shows great potential for the flexible/or
wearable power-conversion devices.
PMID- 28700206
TI - Drug-Porous Silicon Dual Luminescent System for Monitoring and Inhibition of
Wound Infection.
AB - Wound monitoring and curing is of great importance in biomedical research. This
work created a smart bandage that can simultaneously monitor and inhibit wound
infection. The main components of the smart bandage are luminescent porous
silicon (LuPSi) particles loaded with ciprofloxacin (CIP). This dual luminescent
system can undergo accelerated fluorescent color change from red to blue upon the
stimulation of reactive oxygen species (ROS) and elevated pH, which are main
biomarkers in the infected wound. The mechanism behind the chemical-triggered
fluorescent color change was studied in detail. In vitro experiment showed that
the ratiometric fluorescent intensity (IRed/IBlue) of CIP-LuPSi particles
decreased from 10 to 0.03 at pH 7.5 after 24 h, while the value deceased from 10
to 2.15 at pH 7.0. Strong correlation can be also found between the IRed/IBlue
value and ROS concentration ranging from 0.1 to 10 mM. In addition, the oxidation
of LuPSi also simultaneously triggered the release of CIP molecules, which
exhibited bacterial inhibition activity. Therefore, the ratiometric fluorescent
intensity change at red and blue channels can indicate not only the wound
infection status but also the release of antibiotics. In vivo test proved that
the smart bandage could distinguish infected wounds from acute wounds, just
relying on the naked eyes or a cell phone camera. On the basis of the Si
nanotechnology established in this work, theranostic wound care will be realized
in future.
PMID- 28700207
TI - Directed Self-Assembly and Pattern Transfer of Five Nanometer Block Copolymer
Lamellae.
AB - The directed self-assembly (DSA) and pattern transfer of poly(5-vinyl-1,3
benzodioxole-block-pentamethyldisilylstyrene) (PVBD-b-PDSS) is reported. Lamellae
forming PVBD-b-PDSS can form well resolved 5 nm (half-pitch) features in thin
films with high etch selectivity. Reactive ion etching was used to selectively
remove the PVBD block, and fingerprint patterns were subsequently transferred
into an underlying chromium hard mask and carbon layer. DSA of the block
copolymer (BCP) features resulted from orienting PVBD-b-PDSS on guidelines
patterned by nanoimprint lithography. A density multiplication factor of 4* was
achieved through a hybrid chemo-/grapho-epitaxy process. Cross-sectional scanning
tunneling electron microscopy/electron energy loss spectroscopy (STEM/EELS) was
used to analyze the BCP profile in the DSA samples. Wetting layers of parallel
orientation were observed to form unless the bottom and top surface were
neutralized with a surface treatment and top coat, respectively.
PMID- 28700208
TI - Starch Derived Porous Carbon Nanosheets for High-Performance Photovoltaic
Capacitive Deionization.
AB - Capacitive deionization (CDI) is an emerging technology that uniquely integrates
energy storage and desalination. In this work, porous carbon nanosheets (PCNSs)
with an ultrahigh specific surface area of 2853 m2/g were fabricated by the
simple carbonization of starch followed by KOH activation for the electrode
material of photovoltaic CDI. The CDI cell consisting of PCNSs electrodes
exhibited a high salt adsorption capacity (SAC) of 15.6 mg/g at ~1.1 V in 500
mg/L NaCl as well as high charge efficiency and low energy consumption. KOH
activation played a key role in the excellent CDI performance as it not only
created abundant pores on the surface of PCNSs but also made it fluffy and
improved its graphitization degree, which are beneficial to the transport of ions
and electrons. PCNSs are supposed to be a promising candidate for CDI electrode
materials. The combination of solar cells and CDI may provide a new approach to
reduce the energy cost of CDI and boost its commercial competitiveness.
PMID- 28700209
TI - Silicotungstate, a Potential Electron Transporting Layer for Low-Temperature
Perovskite Solar Cells.
AB - Thin films of a heteropolytungstate, lithium silicotungstate (Li4SiW12O40, termed
Li-ST), prepared by a solution process at low temperature, were successfully
applied as electron transporting layer (ETL) of planar-type perovskite solar
cells (PSCs). Dense and uniform Li-ST films were prepared on FTO glass by
depositing a thin Li-ST buffer layer, followed by coating of a main Li-ST layer.
The film thickness was controlled by varying the number of coating cycles,
consisting of spin-coating and thermal treatment at 150 degrees C. In
particular, by employing 60 nm-thick Li-ST layer obtained by two cycles of
coating, the fabricated CH3NH3PbI3 PSC device demonstrates the photovoltaic
conversion efficiency (PCE) of 14.26% with JSC of 22.16 mA cm-2, VOC of 0.993 mV
and FF of 64.81%. The obtained PCE is significantly higher than that of the PSC
employing a TiO2 layer processed at the same temperature (PCE = 12.27%).
Spectroscopic analyses by time-resolved photoluminescence and pulsed light
induced transient measurement of photocurrent indicate that the Li-ST layer
collects electrons from CH3NH3PbI3 more efficiently and also exhibits longer
electron lifetime than the TiO2 layer thermally treated at 150 degrees C. Thus,
Li-ST is considered to be a promising ETL material that can be applied for the
fabrication of flexible PSC devices.
PMID- 28700210
TI - Large In-Plane and Vertical Piezoelectricity in Janus Transition Metal
Dichalchogenides.
AB - Piezoelectricity in 2D van der Waals materials has received considerable interest
because of potential applications in nanoscale energy harvesting, sensors, and
actuators. However, in all the systems studied to date, strain and electric
polarization are confined to the basal plane, limiting the operation of
piezoelectric devices. In this paper, based on ab initio calculations, we report
a 2D materials system, namely, the recently synthesized Janus MXY (M = Mo or W,
X/Y = S, Se, or Te) monolayer and multilayer structures, with large out-of-plane
piezoelectric polarization. For MXY monolayers, both strong in-plane and much
weaker out-of-plane piezoelectric polarizations can be induced by a uniaxial
strain in the basal plane. For multilayer MXY, we obtain a very strong out-of
plane piezoelectric polarization when strained transverse to the basal plane,
regardless of the stacking sequence. The out-of-plane piezoelectric coefficient
d33 is found to be strongest in multilayer MoSTe (5.7-13.5 pm/V depending on the
stacking sequence), which is larger than that of the commonly used 3D
piezoelectric material AlN (d33 = 5.6 pm/V); d33 in other multilayer MXY
structures are a bit smaller, but still comparable. Our study reveals the
potential for utilizing piezoelectric 2D materials and their van der Waals
multilayers in device applications.
PMID- 28700211
TI - Polyphenolic Polymersomes of Temperature-Sensitive Poly(N-vinylcaprolactam)-block
Poly(N-vinylpyrrolidone) for Anticancer Therapy.
AB - We report a versatile synthesis for polyphenolic polymersomes of controlled
submicron (<500 nm) size for intracellular delivery of high and low molecular
weight compounds. The nanoparticles are synthesized by stabilizing the vesicular
morphology of thermally responsive poly(N-vinylcaprolactam)n-b-poly(N
vinylpyrrolidone)m (PVCLn-PVPONm) diblock copolymers with tannic acid (TA), a
hydrolyzable polyphenol, via hydrogen bonding at a temperature above the
copolymer's lower critical solution temperature (LCST). The PVCL179-PVPONm
diblock copolymers are produced by controlled reversible addition-fragmentation
chain transfer (RAFT) polymerization of PVPON using PVCL as a macro-chain
transfer agent. The size of the TA-locked (PVCL179-PVPONm) polymersomes at room
temperature and upon temperature variations are controlled by the PVPON chain
length and TA:PVPON molar unit ratio. The particle diameter decreases from 1000
to 950, 770, and 250 nm with increasing PVPON chain length (m = 107, 166, 205,
234), and it further decreases to 710, 460, 290, and 190 nm, respectively, upon
hydrogen bonding with TA at 50 degrees C. Lowering the solution temperature to
25 degrees C results in a slight size increase for vesicles with longer PVPON.
We also show that TA-locked polymersomes can encapsulate and store the anticancer
drug doxorubicin (DOX) and higher molecular weight fluorescein isothiocyanate
(FITC)-dextran in a physiologically relevant pH and temperature range.
Encapsulated DOX is released in the nuclei of human alveolar adenocarcinoma tumor
cells after 6 h incubation via biodegradation of the TA shell with the
cytotoxicity of DOX-loaded polymersomes being concentration-dependent. Our
approach offers biocompatible and intracellular degradable nanovesicles of
controllable size for delivery of a variety of encapsulated materials.
Considering the particle monodispersity, high loading capacity, and a facile two
step aqueous assembly based on the reversible temperature-responsiveness of PVCL,
these polymeric vesicles have significant potential as novel drug nanocarriers
and provide a new perspective for fundamental studies on thermo-triggered polymer
assemblies in solutions.
PMID- 28700212
TI - Nuclear Magnetic Resonance Structure of an 8 * 8 Nucleotide RNA Internal Loop
Flanked on Each Side by Three Watson-Crick Pairs and Comparison to Three
Dimensional Predictions.
AB - The prediction of RNA three-dimensional structure from sequence alone has been a
long-standing goal. High-resolution, experimentally determined structures of
simple noncanonical pairings and motifs are critical to the development of
prediction programs. Here, we present the nuclear magnetic resonance structure of
the (5'CCAGAAACGGAUGGA)2 duplex, which contains an 8 * 8 nucleotide internal loop
flanked by three Watson-Crick pairs on each side. The loop is comprised of a
central 5'AC/3'CA nearest neighbor flanked by two 3RRs motifs, a known stable
motif consisting of three consecutive sheared GA pairs. Hydrogen bonding patterns
between base pairs in the loop, the all-atom root-mean-square deviation for the
loop, and the deformation index were used to compare the structure to automated
predictions by MC-sym, RNA FARFAR, and RNAComposer.
PMID- 28700213
TI - Enabling Graded and Large-Scale Multiplex of Desired Genes Using a Dual-Mode
dCas9 Activator in Saccharomyces cerevisiae.
AB - Standard approaches for dCas9-based modification of gene expression are limited
in the ability to multiplex targets, establish streamlined cassettes, and utilize
commonly studied Pol II promoters. In this work, we repurpose the dCas9-VPR
activator to act as a dual-mode activator/repressor that can be programmed solely
on the basis of target position at gene loci. Furthermore, we implement this
approach using a streamlined Pol II-ribozyme system that allows expression of
many sgRNAs from a single transcript. By "stepping" dCas9-VPR within the promoter
region and ORF we create graded activation and repression (respectively) of
target genes, allowing precise control over multiplexed gene modulation.
Expression from the Pol II system increased the net amount of sgRNA production in
cells by 3.88-fold relative to the Pol III SNR52 promoter, leading to a
significant improvement in dCas9-VPR repression strength. Finally, we utilize our
Pol II system to create galactose-inducible switching of gene expression states
and multiplex constructs capable of modulating up to 4 native genes from a single
vector. Our approach represents a significant step toward minimizing DNA required
to assemble CRISPR systems in eukaryotes while enhancing the efficacy (greater
repression strength), scale (more sgRNAs), and scope (inducibility) of dCas9
mediated gene regulation.
PMID- 28700214
TI - Capacitive Neutralization Dialysis for Direct Energy Generation.
AB - Capacitive neutralization dialysis energy (CNDE) is proposed as a novel energy
harvesting technique that is able to utilize waste acid and alkaline solutions to
produce electrical energy. CNDE is a modification based on neutralization
dialysis. It was found that a higher NaCl concentration led to a higher open
circuit potential when the concentrations of acid and alkaline solutions were
fixed. Upon closing of the circuit, the membrane potential was used as a driving
force to move counter ions into the electrical double layers at the electrode
liquid interface, thereby creating an ionic current. Correspondingly, in the
external circuit, electrons flow through an external resistor from one electrode
to the other, thereby generating electrical energy directly. The influence of
external resistances was studied to achieve greater energy extraction, with the
maximum output of 110 mW/m2 obtained by employing an external resistance of 5
Omega together with the AC-coated electrode.
PMID- 28700215
TI - Roles of Transport Limitations and Mineral Heterogeneity in Carbonation of
Fractured Basalts.
AB - Basalt formations could enable secure long-term carbon storage by trapping
injected CO2 as stable carbonates. Here, a predictive modeling framework was
designed to evaluate the roles of transport limitations and mineral spatial
distributions on mineral dissolution and carbonation reactions in fractured
basalts exposed to CO2-acidified fluids. Reactive transport models were developed
in CrunchTope based on data from high-temperature, high-pressure flow-through
experiments. Models isolating the effect of transport compared nine flow
conditions under the same mineralogy. Heterogeneities were incorporated by
segmenting an actual reacted basalt sample, and these results were compared to
equivalent flow conditions through randomly generated mineral distributions with
the same bulk composition. While pure advective flow with shorter retention times
promotes rapid initial carbonation, pure diffusion sustains mineral reactions for
longer time frames and generates greater net carbonate volumes. For the same
transport conditions and bulk composition, exact mineral spatial distributions do
not impact the amount of carbonation but could determine the location by
controlling local solution saturation with respect to secondary carbonates. In
combination, the results indicate that bulk mineralogy will be more significant
than small-scale heterogeneities in controlling the rate and extent of CO2
mineralization, which will likely occur in diffusive zones adjacent to flow paths
or in dead-end fractures.
PMID- 28700216
TI - Accelerated Lifetime Testing of Organic-Inorganic Perovskite Solar Cells
Encapsulated by Polyisobutylene.
AB - Metal halide perovskite solar cells (PSCs) have undergone rapid progress.
However, unstable performance caused by sensitivity to environmental moisture and
high temperature is a major impediment to commercialization of PSCs. In the
present work, a low-temperature, glass-glass encapsulation technique using high
performance polyisobutylene (PIB) as the moisture barrier is investigated on
planar glass/FTO/TiO2/FAPbI3/PTAA/gold perovskite solar cells. PIB was applied as
either an edge seal or blanket layer. Electrical connections to the encapsulated
PSCs were provided by either the FTO or Au layers. Results of a "calcium test"
demonstrated that a PIB edge-seal effectively prevents moisture ingress. A shelf
life test was performed and the PIB-sealed PSC was stable for at least 200 days.
Damp heat and thermal cycling tests, in compliance with IEC61215:2016, were used
to evaluate different encapsulation methods. Current-voltage measurements were
performed regularly under simulated AM1.5G sunlight to monitor changes in PCE.
The best results we have achieved to date maintained the initial efficiency after
540 h of damp heat testing and 200 thermal cycles. To the best of the authors'
knowledge, these are among the best damp heat and thermal cycle test results for
perovskite solar cells published to date. Given the modest performance of the
cells (8% averaged from forward and reverse scans) especially with the more
challenging FAPbI3 perovskite material tested in this work, it is envisaged that
better stability results can be further achieved when higher performance
perovskite solar cells are encapsulated using the PIB packaging techniques
developed in this work. We propose that heat rather than moisture was the main
cause of our PSC degradation. Furthermore, we propose that preventing the escape
of volatile decomposition products from the perovskite solar cell materials is
the key for stability. PIB encapsulation is a very promising packaging solution
for perovskite solar cells, given its demonstrated effectiveness, ease of
application, low application temperature, and low cost.
PMID- 28700217
TI - Mechanisms of Symmetry Breaking in a Multidimensional Flashing Particle Ratchet.
AB - Ratcheting is a mechanism that produces directional transport of particles by
rectifying nondirectional energy using local asymmetries rather than a net bias
in the direction of transport. In a flashing ratchet, an oscillating force (here,
an AC field) is applied perpendicular to the direction of transport. In an effort
to explore the properties of current experimentally realizable ratchet systems,
and to design new ones, this paper describes classical simulations of a damped
flashing ratchet that transports charged nanoparticles within a transport layer
of finite, non-zero thickness. The thickness of the layer, and the decay of the
applied field in the z-direction throughout that thickness, provide a mechanism
of symmetry breaking in the system that allows the ratchet to produce directional
transport using a temporally unbiased oscillation of the AC driving field, a sine
wave. Sine waves are conveniently produced experimentally or harvested from
natural sources but cannot produce transport in a 1D or pseudo-1D system. The
sine wave drive produces transport velocities an order of magnitude higher than
those produced by the common on/off drive, but lower than those produced by a
temporally biased square wave drive (unequal durations of the positive and
negative states). The dependence of the particle velocity on the thickness of the
transport layer, and on the homogeneity of the oscillating field within the
layer, is presented for all three driving schemes.
PMID- 28700218
TI - Response of Soil Microbial Communities to Elevated Antimony and Arsenic
Contamination Indicates the Relationship between the Innate Microbiota and
Contaminant Fractions.
AB - Mining of sulfide ore deposits containing metalloids, such as antimony and
arsenic, has introduced serious soil contamination around the world, posing
severe threats to food safety and human health. Hence, it is important to
understand the behavior and composition of the microbial communities that control
the mobilization or sequestration of these metal(loid)s. Here, we selected two
sites in Southwest China with different levels of Sb and As contamination to
study interactions among various Sb and As fractions and the soil microbiota,
with a focus on the microbial response to metalloid contamination. Comprehensive
geochemical analyses and 16S rRNA gene amplicon sequencing demonstrated distinct
soil taxonomic inventories depending on Sb and As contamination levels.
Stochastic gradient boosting indicated that citric acid extractable Sb(V) and
As(V) contributed 5% and 15%, respectively, to influencing the community
diversity. Random forest predicted that low concentrations of Sb(V) and As(V)
could enhance the community diversity but generally, the Sb and As contamination
impairs microbial diversity. Co-occurrence network analysis indicated a strong
correlation between the indigenous microbial communities and various Sb and As
fractions. A number of taxa were identified as core genera due to their elevated
abundances and positive correlation with contaminant fractions (total Sb and As
concentrations, bioavailable Sb and As extractable fractions, and Sb and As redox
species). Shotgun metagenomics indicated that Sb and As biogeochemical redox
reactions may exist in contaminated soils. All these observations suggest the
potential for bioremediation of Sb- and As-contaminated soils.
PMID- 28700219
TI - Versatile Site-Selective Protein Reaction Guided by WW Domain-Peptide Motif
Interaction.
AB - A short, flexible, and unstructured peptide tag that has versatile and facile use
in protein labeling applications is highly desirable. Here, we report an 11
residue peptide tag with an internal cysteine (a W-tag, derived from a Comm PY
peptide motif that is known to bind with Nedd4 WW3* domain) that can be installed
at different regions of the target protein without compromising its covalent
reactivity with the reactive label (a 35-residue synthetic Nedd4 WW3* domain
derivative). This versatility is explained by the unique structural features of
the reaction. NMR analysis reveals that both the W-tag peptide and reactive Nedd4
WW3* protein are unstructured before they encounter each other. The binding
interaction of the two induces noticeable structural changes and promotes global
folding. Consequently, the reactive cysteine residue at W-tag and the
electrophilic chloroacetyl group at Nedd4 WW3* domain are positioned to be in
close proximity, inducing an intermolecular covalent cross-linking. The covalent
linkage in turn stabilizes the folding of the protein complex. This unique
multistep mechanism renders this labeling reaction amenable to different sites of
the proteins of interest: installation of the tag at N- and C-termini, in the
flexible linker region, in the loop region, and the extracellular terminus of
target proteins exhibited comparable reactivity. This work therefore represents
the first proximity-induced cysteine reaction based on the unique binding
features of WW domains that demonstrates unprecedented versatility.
PMID- 28700220
TI - Mechanistic Characterization of Escherichia coli l-Aspartate Oxidase from Kinetic
Isotope Effects.
AB - l-Aspartate oxidase, encoded by the nadB gene, is the first enzyme in the de novo
synthesis of NAD+ in bacteria. This FAD-dependent enzyme catalyzes the oxidation
of l-aspartate to generate iminoaspartate and reduced flavin. Distinct from most
amino acid oxidases, it can use either molecular oxygen or fumarate to reoxidize
the reduced enzyme. Sequence alignments and the three-dimensional crystal
structure have revealed that the overall fold and catalytic residues of NadB
closely resemble those of the succinate dehydrogenase/fumarate reductase family
rather than those of the prototypical d-amino acid oxidases. This suggests that
the enzyme can catalyze amino acid oxidation via typical amino acid oxidase
chemistry, involving the removal of protons from the alpha-amino group and the
transfer of the hydride from C2, or potentially deprotonation at C3 followed by
transfer of the hydride from C2, similar to chemistry occurring during succinate
oxidation. We have investigated this potential mechanistic ambiguity using a
combination of primary, solvent, and multiple deuterium kinetic isotope effects
in steady state experiments. Our results indicate that the chemistry is similar
to that of typical amino acid oxidases in which the transfer of the hydride from
C2 of l-aspartate to FAD is rate-limiting and occurs in a concerted manner with
respect to deprotonation of the alpha-amine. Together with previous kinetic and
structural data, we propose that NadB has structurally evolved from succinate
dehydrogenase/fumarate reductase-type enzymes to gain the new functionality of
oxidizing amino acids while retaining the ability to reduce fumarate.
PMID- 28700221
TI - Transuranic Hybrid Materials: Crystallographic and Computational Metrics of
Supramolecular Assembly.
AB - Assembly of a family of 12 supramolecular compounds containing [AnO2Cl4]2- (An =
U, Np, Pu), via hydrogen and halogen bonds donated by substituted 4-X-pyridinium
cations (X = H, Cl, Br, I), is reported. These materials were prepared from a
room-temperature synthesis wherein crystallization of unhydrolyzed and valence
pure [An(VI)O2Cl4]2- (An = U, Np, Pu) tectons is the norm. We present a hierarchy
of assembly criteria based on crystallographic observations and subsequently
quantify the strengths of the non-covalent interactions using Kohn-Sham density
functional calculations. We provide, for the first time, a detailed description
of the electrostatic potentials of the actinyl tetrahalide dianions and reconcile
crystallographically observed structural motifs and non-covalent interaction
acceptor-donor pairings. Our findings indicate that the average electrostatic
potential across the halogen ligands (the acceptors) changes by only ~2 kJ mol-1
across the AnO22+ series, indicating that the magnitude of the potential is
independent of the metal center. The role of the cation is therefore critical in
directing structural motifs and dictating the resulting hydrogen and halogen bond
strengths, the former being stronger due to the positive charge centralized on
the pyridyl nitrogen, N-H+. Subsequent analyses using the quantum theory of atoms
in molecules and natural bond orbital approaches support this conclusion and
highlight the structure-directing role of the cations. Whereas one can infer that
Columbic attraction is the driver for assembly, the contribution of the non
covalent interaction is to direct the molecular-level arrangement (or
disposition) of the tectons.
PMID- 28700222
TI - Bioavailability of Carbon Nanomaterial-Adsorbed Polycyclic Aromatic Hydrocarbons
to Pimphales promelas: Influence of Adsorbate Molecular Size and Configuration.
AB - Despite carbon nanomaterials' (CNMs) potential to alter the bioavailability of
adsorbed contaminants, information characterizing the relationship between
adsorption behavior and bioavailability of CNM-adsorbed contaminants is still
limited. To investigate the influence of CNM morphology and organic contaminant
(OC) physicochemical properties on this relationship, adsorption isotherms were
generated for a suite of polycyclic aromatic hydrocarbons (PAHs) on multiwalled
carbon nanotubes (MWCNTs) and exfoliated graphene (GN) in conjunction with
determining the bioavailability of the adsorbed PAHs to Pimphales promelas using
bile analysis via fluorescence spectroscopy. Although it appeared that GN
adsorbed PAHs indiscriminately compared to MWCNTs, the subsequent bioavailability
of GN-adsorbed PAHs was more sensitive to PAH morphology than MWCNTs. GN was
effective at reducing bioavailability of linear PAHs by ~70%, but had little
impact on angular PAHs. MWCNTs were sensitive to molecular size, where
bioavailability of two-ringed naphthalene was reduced by ~80%, while
bioavailability of the larger PAHs was reduced by less than 50%. Furthermore, the
reduction in bioavailability of CNM-adsorbed PAHs was negatively correlated with
the amount of CNM surface area covered by the adsorbed-PAHs. This study shows
that the variability in bioavailability of CNM-adsorbed PAHs is largely driven by
PAH size, configuration and surface area coverage.
PMID- 28700223
TI - Metabolomics Profiling to Determine the Effect of Postmortem Aging on Color and
Lipid Oxidative Stabilities of Different Bovine Muscles.
AB - The objective of this study was to identify metabolites that could be associated
with oxidative stability of aged bovine muscles. Three muscles (longissimus
lumbrum (LL), semimembranosus (SM), and psoas major (PM)) from seven beef
carcasses at 1 day postmortem were divided into three sections and assigned to
three aging periods (9, 16, and 23 days). Although an increase in discoloration
was found in all muscles with aging, LL was the most color/lipid oxidative
stable, followed by SM and PM (P < 0.05). Lower myoglobin and nonheme iron
contents were observed in LL compared to those in SM and PM (P < 0.05). The HPLC
ESI-MS-based metabolomics analysis identified metabolites that were significantly
responsive to aging and/or muscle type, such as acyl carnitines, free amino
acids, nucleotides, nucleosides, and glucuronides. The results from the current
study suggest that color and oxidative stability could be associated with aging
but are also muscle-specific. Further studies determining the exact role of the
identified metabolites in the color and oxidative stability of beef muscles are
warranted.
PMID- 28700224
TI - Cu-Catalyzed Hydrocarbonylative C-C Coupling of Terminal Alkynes with Alkyl
Iodides.
AB - A Cu-catalyzed hydrocarbonylative C-C coupling of terminal alkynes with
unactivated alkyl iodides has been developed, enabling highly chemo- and
regioselective synthesis of unsymmetrical dialkyl ketones. A variety of
functional groups are tolerated, and both primary and secondary alkyl iodides
react well. An autotandem sequence of two Cu-catalyzed processes is proposed:
first hydrocarbonylative coupling of the alkyne and the alkyl iodide, followed by
reduction of the intermediate unsaturated ketone to the saturated product.
Mechanistic experiments indicate that an alkenylcopper intermediate activates the
alkyl iodide by single electron transfer to enable a radical carbonylation
pathway.
PMID- 28700225
TI - Combining Elements from Two Antagonists of Formyl Peptide Receptor 2 Generates
More Potent Peptidomimetic Antagonists.
AB - Structural optimization of a peptidomimetic antagonist of formyl peptide receptor
2 (FPR2) was explored by an approach involving combination of elements from the
two most potent FPR2 antagonists described: a Rhodamine B-conjugated 10-residue
gelsonin-derived peptide (i.e., PBP10, RhB-QRLFQVKGRR-OH) and the palmitoylated
alpha-peptide/beta-peptoid hybrid Pam-(Lys-betaNspe)6-NH2. This generated an
array of hybrid compounds from which a new subclass of receptor-selective
antagonists was identified. The most potent representatives displayed activity in
the low nanomolar range. The resulting stable and potent FPR2-selective
antagonists (i.e., RhB-(Lys-betaNphe)n-NH2; n = 4-6) are expected to become
valuable tools in further elucidation of the physiological role of FPR2 in health
and disease.
PMID- 28700226
TI - Cyclobutene vs 1,3-Diene Formation in the Gold-Catalyzed Reaction of Alkynes with
Alkenes: The Complete Mechanistic Picture.
AB - The intermolecular gold(I)-catalyzed reaction between arylalkynes and alkenes
leads to cyclobutenes by a [2 + 2] cycloaddition, which takes place stepwise,
first by formation of cyclopropyl gold(I) carbenes, followed by a ring expansion.
However, 1,3-butadienes are also formed in the case of ortho-substituted
arylalkynes by a metathesis-type process. The corresponding reaction of alkenes
with aryl-1,3-butadiynes, ethynylogous to arylalkynes, leads exclusively to
cyclobutenes. A comprehensive mechanism for the gold(I)-catalyzed reaction of
alkynes with alkenes is proposed on the basis of density functional theory
calculations, which shows that the two pathways leading to cyclobutenes or dienes
are very close in energy. The key intermediates are cyclopropyl gold(I) carbenes,
which have been independently generated by retro-Buchner reaction from
stereodefined 1a,7b-dihydro-1H-cyclopropa[a]naphthalenes.
PMID- 28700227
TI - Practical and Asymmetric Reductive Coupling of Isoquinolines Templated by Chiral
Diborons.
AB - We herein describe a chiral diboron-templated highly diastereoselective and
enantioselective reductive coupling of isoquinolines that provided expedited
access to a series of chiral substituted bisisoquinolines in good yields and
excellent ee's under mild conditions. The method enjoys a broad substrate scope
and good functional group compatibility. Mechanistic investigation suggests the
reaction proceeds through a concerted [3,3]-sigmatropic rearrangement.
PMID- 28700228
TI - Structural Evolution of Three-Component Nanoparticles in Polymer Nanoreactors.
AB - Recent developments in scanning probe block copolymer lithography (SPBCL) enable
the confinement of multiple metal precursors in a polymer nanoreactor and their
subsequent transformation into a single multimetallic heterostructured
nanoparticle through thermal annealing. However, the process by which
multimetallic nanoparticles form in SPBCL-patterned nanoreactors remains unclear.
Here, we utilize the combination of PEO-b-P2VP and Au, Ag, and Cu salts as a
model three-component system to investigate this process. The data suggest that
the formation of single-component Au, Ag, or Cu nanoparticles within polymer
nanoreactors consists of two stages: (I) nucleation, growth, and coarsening of
the particles to yield a single particle in each reactor; (II) continued particle
growth by depletion of the remaining precursor in the reactor until the particle
reaches a stable size. Also, different aggregation rates are observed for single
component particle formation (Au > Ag > Cu). This behavior is also observed for
two-component systems, where nucleation sites have greater Au content than the
other metals. This information can be used to trap nanoparticles with kinetic
structures. High-temperature treatment ultimately facilitates the structural
evolution of the kinetic particle into a particle with a fixed structure.
Therefore, with multicomponent systems, a third stage that involves elemental
redistribution within the particle must be part of the description of the
synthetic process. This work not only provides a glimpse at the mechanism
underlying multicomponent nanoparticle formation in SPBCL-generated nanoreactors
but also illustrates, for the first time, the utility of SPBCL as a platform for
controlling the architectural evolution of multimetallic nanoparticles in
general.
PMID- 28700229
TI - Fabrication of Novel Avermectin Nanoemulsion Using a Polyurethane Emulsifier with
Cleavable Disulfide Bonds.
AB - In this study, a polyurethane emulsifer with various functional groups was
prepared from isophorone diisocyanate, avermectin, 2,2-dimethylol propionic acid,
and bis(2-hydroxyethyl) disulfide. The chemical structure of the polymer was
confirmed by Fourier transform infrared spectroscopy, proton nuclear magnetic
resonance, and element analysis. The polymer exhibited adequate emulsification
ability for avermectin after neutralization with triethylamine. A satisfaying
nanoemulsion was obtained, in which avermectin was encapsulated in nanoparticles
with 50 wt % drug loading, low organic solvent content, and high stability under
dilution and centrifuging treatment in addition to low surface tension, high
affinity to crop leaf, and improved avermectin photostability. The resulting
nanoparticles showed degradability in the presence of dl-dithiothreitol or inside
the insect as a result of the disulfide bonds, promoting the release of
avermectin. As a result, the avermectin nanoparticles showed higher insecticidal
ability compared to both the avermectin nanoparticles without a disulfide group
and the avermectin emulsifiable concentrate.
PMID- 28700230
TI - LigQ: A Webserver to Select and Prepare Ligands for Virtual Screening.
AB - Virtual screening is a powerful methodology to search for new small molecule
inhibitors against a desired molecular target. Usually, it involves evaluating
thousands of compounds (derived from large databases) in order to select a set of
potential binders that will be tested in the wet-lab. The number of tested
compounds is directly proportional to the cost, and thus, the best possible set
of ligands is the one with the highest number of true binders, for the smallest
possible compound set size. Therefore, methods that are able to trim down large
universal data sets enriching them in potential binders are highly appreciated.
Here we present LigQ, a free webserver that is able to (i) determine best
structure and ligand binding pocket for a desired protein, (ii) find known
binders, as well as potential ligands known to bind to similar protein domains,
(iii) most importantly, select a small set of commercial compounds enriched in
potential binders, and (iv) prepare them for virtual screening. LigQ was tested
with several proteins, showing an impressive capacity to retrieve true ligands
from large data sets, achieving enrichment factors of over 10%. LigQ is available
at http://ligq.qb.fcen.uba.ar/ .
PMID- 28700231
TI - The hpCADD NDDO Hamiltonian: Parametrization.
AB - A neglect of diatomic differential overlap (NDDO) Hamiltonian has been
parametrized as an electronic component of a polarizable force field. Coulomb and
exchange potentials derived directly from the NDDO Hamiltonian in principle can
be used with classical potentials, thus forming the basis for a new generation of
efficiently applicable multipolar polarizable force fields. The new hpCADD
Hamiltonian uses force-field-like atom types and reproduces the electrostatic
properties (dipole moment, molecular electrostatic potential) and Koopmans'
theorem ionization potentials closely, as demonstrated for a large training set
and an independent test set of small molecules. The Hamiltonian is not intended
to reproduce geometries or total energies well, as these will be controlled by
the classical force-field potentials. In order to establish the hpCADD
Hamiltonian as an electronic component in force-field-based calculations, we
tested its performance in combination with the 3D reference interaction site
model (3D RISM) for aqueous solutions. Comparison of the resulting solvation free
energies for the training and test sets to atomic charges derived from standard
procedures, exact solute-solvent electrostatics based on high-level quantum
chemical reference data, and established semiempirical Hamiltonians demonstrates
the advantages of the hpCADD parametrization.
PMID- 28700232
TI - Revealing the Role of Interfacial Properties on Catalytic Behaviors by in Situ
Surface-Enhanced Raman Spectroscopy.
AB - Insightful understanding of how interfacial structures and properties affect
catalytic processes is one of the most challenging issues in heterogeneous
catalysis. Here, the essential roles of Pt-Au and Pt-oxide-Au interfaces on the
activation of H2 and the hydrogenation of para-nitrothiophenol (pNTP) were
studied at molecular level by in situ surface-enhanced Raman spectroscopy (SERS)
and shell-isolated nanoparticle-enhanced Raman spectroscopy (SHINERS). Pt-Au and
Pt-oxide-Au interfaces were fabricated through the synthesis of Pt-on-Au and Pt
on-SHINs nanocomposites. Direct spectroscopic evidence demonstrates that the
atomic hydrogen species generated on the Pt nanocatalysts can spill over from Pt
to Au via the Pt-Au and Pt-TiO2-Au interfaces, but would be blocked at the Pt
SiO2-Au interfaces, leading to the different reaction pathways and product
selectivity on Pt-on-Au and Pt-on-SHINs nanocomposites. Such findings have also
been verified by the density functional theory calculation. In addition, it is
found that nanocatalysts assembled on pinhole-free shell-isolated nanoparticles
(Pt-on-pinhole-free-SHINs) can override the influence of the Au core on the
reaction and can be applied as promising platforms for the in situ study of
heterogeneous catalysis. This work offers a concrete example of how SERS/SHINERS
elucidate details about in situ reaction and helps to dig out the fundamental
role of interfaces in catalysis.
PMID- 28700233
TI - Excited-State Gradients in Polarizable QM/MM Models: An Induced Dipole
Formulation.
AB - Charge and structural relaxation of electronically excited states in embedded
systems are strongly affected by the environment. It is known that the largest
part of environment effects comes from electrostatics. However, polarization can
also play a role by tuning the electronic and geometrical properties of the
states, finally modifying the fluorescence. Here we present the formulation of
analytical excited-state gradients within a polarizable QM/MM approach and their
implementation within the ONIOM framework. A time-dependent DFT level of theory
is used in combination with an induced dipole formulation of the polarizable
embedding. The formation and relaxation of the bright excited state of an organic
dye (DAPI) intercalated in a DNA pocket is used to quantify the role played by
the mutual polarization between the QM subsystem and the embedding and also to
investigate the onset of overpolarization, which is a known limit of the model
with potentially detrimental effects. On the one hand, the results indicate the
robustness of the QM-classical interface and, on the other hand, show the non
negligible effect of polarization between DAPI and a DNA pocket in determining
the fluorescence properties of the embedded dye.
PMID- 28700234
TI - Assessment of Tuned Range Separated Exchange Functionals for Spectroscopies and
Properties of Uranium Complexes.
AB - The Kohn-Sham delocalization error (DE) is quantified in select uranium compounds
for various functionals and shown to correlate with the magnitude of dative
ligand donation into the 5f shell. Range separated exchange functionals are
reparametrized to minimize the DE and analyzed for their spectroscopic predictive
capabilities. Valence excitation spectra of occupied 5f systems exhibit
noticeable improvement upon reparametrization, e.g. UCl6-, UCl62-, and UO2+. Less
sensitivity to the reparameterization was observed for closed shell 5f systems
and core excitation spectra. A general parametrization is proposed to perform
well for valence excitation spectra with small DE.
PMID- 28700235
TI - Quantitative CrAssphage PCR Assays for Human Fecal Pollution Measurement.
AB - Environmental waters are monitored for fecal pollution to protect public health
and water resources. Traditionally, general fecal-indicator bacteria are used;
however, they cannot distinguish human fecal waste from other animal pollution
sources. Recently, a novel bacteriophage, crAssphage, was discovered by
metagenomic data mining and reported to be abundant in and closely associated
with human fecal waste. To confirm bioinformatic predictions, 384 primer sets
were designed along the length of the crAssphage genome. Based on initial
screening, two novel crAssphage qPCR assays (CPQ_056 and CPQ_064) were designed
and evaluated in reference fecal samples and water matrices. The assays exhibited
high specificities (98.6%) when tested against an animal fecal reference library,
and crAssphage genetic markers were highly abundant in raw sewage and sewage
impacted water samples. In addition, CPQ_056 and CPQ_064 performance was compared
to HF183/BacR287 and HumM2 assays in paired experiments. Findings confirm that
viral crAssphage qPCR assays perform at a similar level to well-established
bacterial human-associated fecal-source-identification approaches. These new
viral-based assays could become important water quality management and research
tools.
PMID- 28700236
TI - Equivalence of the Floquet-Magnus and Fer Expansions to Investigate the Dynamics
of a Spin System in the Three-Level System.
AB - In this work, we investigated the orders to which the Floquet-Magnus expansion
(FME) and Fer expansion (FE) are equivalent or different for the three-level
system. Specifically, we performed the third-order calculations of both
approaches based on elegant integrations formalism. We present an important close
relationship between the Floquet-Magnus and Fer expansions. As the propagator
from the FME takes the form of the evolution operator, which removes the
constraint of a stroboscopic observation, we appreciated the effects of time
evolution under Hamiltonians with different orders separately. Our work unifies
and generalizes existing results of Floquet-Magnus and Fer approaches and
delivers illustrations of novel springs that boost previous applications that are
based on the classical information. Due to the lack of an unequivocal
relationship between the FME and FE, some disagreements between the results
produced by these theories will be found, especially in NMR experiments. Our
results can find applications in the optimization of NMR spectroscopy, quantum
computation, quantum optical control, and coherence in optics and might bear new
awareness in fundamental perusals of quantum spin dynamics. This work is an
important theoretical and numerical contribution in the general field of spin
dynamics.
PMID- 28700238
TI - Regio- and Stereoselective Anti-Carbozincation of Alkynyl Ethers Using ZnBr2
toward (Z)-beta-Zincated Enol Ether Synthesis.
AB - (Z)-beta-Aryloxyalkenylzincs are synthesized stereoselectively via anti
carbozincation among alkynyl ethers, silyl ketene acetals, and ZnBr2. X-ray
analysis revealed the structure of the zinc species is a mononuclear two
coordinate dialkenylzinc that is transformed into functionalized enol ethers as a
single isomer in the reaction of various electrophiles.
PMID- 28700237
TI - RGD-Modified Albumin Nanoconjugates for Targeted Delivery of a Porphyrin
Photosensitizer.
AB - Advances in photodynamic therapy of cancer have been restrained by lack of cancer
specificity and side effects to normal tissues. Molecularly targeted photodynamic
therapy can achieve higher cancer specificity by combination of active cancer
targeting and localized laser activation. We aimed to use albumin as a carrier to
prepare targeted nanoconjugates that are selective to cancer cells and smaller
than conventional nanoparticles for superior tumor penetration. IRDye 700DX
(IR700), a porphyrin photosensitizer, was covalently conjugated to human serum
albumin that was also linked with tumor-targeting RGD peptides. With multiple
IR700 and RGD molecules in a single albumin molecule, the resultant
nanoconjugates demonstrated monodispersed and uniform size distribution with a
diameter of 10.9 nm. These targeted nanoconjugates showed 121-fold increase in
cellular delivery of IR700 into TOV21G ovarian cancer cells compared to control
nanoconjugates. Mechanistic studies revealed that the integrin specific cellular
delivery was achieved through dynamin-mediated caveolae-dependent endocytosis
pathways. They produced massive cell killing in TOV21G cells at low nanomolar
concentrations upon light irradiation, while NIH/3T3 cells that do not express
integrin alphavbeta3 were not affected. Because of their small size, targeted
albumin nanoconjugates could penetrate tumor spheroids of SKOV-3 ovarian cancer
cells and produced strong phototoxicity in this 3-D model. Owing to their cancer
specific delivery and small size, these targeted nanoconjugates may become an
effective drug delivery system for enabling molecularly targeted photodynamic
therapy of cancer.
PMID- 28700239
TI - Suppressing Nucleation in Metal-Organic Chemical Vapor Deposition of MoS2
Monolayers by Alkali Metal Halides.
AB - Toward the large-area deposition of MoS2 layers, we employ metal-organic
precursors of Mo and S for a facile and reproducible van der Waals epitaxy on c
plane sapphire. Exposing c-sapphire substrates to alkali metal halide salts such
as KI or NaCl together with the Mo precursor prior to the start of the growth
process results in increasing the lateral dimensions of single crystalline
domains by more than 2 orders of magnitude. The MoS2 grown this way exhibits high
crystallinity and optoelectronic quality comparable to single-crystal MoS2
produced by conventional chemical vapor deposition methods. The presence of
alkali metal halides suppresses the nucleation and enhances enlargement of
domains while resulting in chemically pure MoS2 after transfer. Field-effect
measurements in polymer electrolyte-gated devices result in promising electron
mobility values close to 100 cm2 V-1 s-1 at cryogenic temperatures.
PMID- 28700240
TI - The Curious Case of 2-Propyl-1H-benzimidazole in the Solid State: An Experimental
and Theoretical Study.
AB - 2-Propyl-1H-benzimidazole (2PrBzIm) is a small molecule, commercially available,
which displays a curious behavior in the solid state. 2PrBzIm, although devoid of
chirality by fast rotation about a single bond of the propyl group in solution,
crystallizes as a conglomerate showing chiroptical properties. An exhaustive
analysis of its crystal structure and a wide range of experiments monitored by
vibrational circular dichroism spectroscopy eliminated all possibilities of an
artifact. What remains is a new example of the unexplained phenomenon of
persistent supramolecular chirality.
PMID- 28700241
TI - Direct Observation of "Pac-Man" Coarsening.
AB - We report direct observation of a "Pac-Man" like coarsening mechanism of a self
supporting thin film of nickel oxide. The ultrathin film has an intrinsic
morphological instability due to surface stress leading to the development of
local thicker regions at step edges. Density functional theory calculations and
continuum modeling of the elastic instability support the model for the process.
PMID- 28700242
TI - P-N Conversion in a Water-Ionic Liquid Binary System for Nonredox
Thermocapacitive Converters.
AB - An intriguing p-n conversion of thermoelectric property was observed in a water
ionic liquid ([EMIm][Ac]) binary system with precise control over water content.
The highest p-type and n-type Seebeck coefficient were optimized at water
[EMIm][Ac] molar ratio of 2:1 and 4:1, respectively. DFT calculation illustrates
that a configuration of solvent separation ion pairs is preferred at the water
[EMIm][Ac] molar ratio of 4:1, leading to the p-n conversion through weakening
interaction between anion clusters and gold electrodes. Furthermore, p-n
thermocapacitive converters were integrated to enhance the output Seebeck
voltages. This work opens up new perspectives for harvesting low grade heat with
the use of fluidic materials.
PMID- 28700243
TI - Impact of Wildfire Emissions on Chloride and Bromide Depletion in Marine Aerosol
Particles.
AB - This work examines particulate chloride (Cl-) and bromide (Br-) depletion in
marine aerosol particles influenced by wildfires at a coastal California site in
the summers of 2013 and 2016. Chloride exhibited a dominant coarse mode due to
sea salt influence, with substantially diminished concentrations during fire
periods as compared to nonfire periods. Bromide exhibited a peak in the
submicrometer range during fire and nonfire periods, with an additional
supermicrometer peak in the latter periods. Chloride and Br- depletions were
enhanced during fire periods as compared to nonfire periods. The highest observed
%Cl- depletion occurred in the submicrometer range, with maximum values of 98.9%
(0.32-0.56 MUm) and 85.6% (0.56-1 MUm) during fire and nonfire periods,
respectively. The highest %Br- depletion occurred in the supermicrometer range
during fire and nonfire periods with peak depletion between 1.8-3.2 MUm (78.8%
and 58.6%, respectively). When accounting for the neutralization of sulfate by
ammonium, organic acid particles showed the greatest influence on Cl- depletion
in the submicrometer range. These results have implications for aerosol
hygroscopicity and radiative forcing in areas with wildfire influence owing to
depletion effects on composition.
PMID- 28700244
TI - Targeted Yttrium 89-Doxorubicin Drug-Eluting Bead-A Safety and Feasibility Pilot
Study in a Rabbit Liver Cancer Model.
AB - The purpose of this article is to evaluate feasibility and safety of the cancer
targeting (radio)-chemoembolization drug-eluting bead (TRCE-DEB) concept drug
SW43-DOX-L-NETA(89Y) DEB for the intra-arterial treatment of VX2 rabbit liver
tumors. The treatment compound comprises of the sigma-2 receptor ligand SW43 for
cancer targeting, doxorubicin (DOX), and 89yttrium (89Y) as nonradioactive
surrogate for therapeutic (yttrium-90, lutetium-177) and imaging (yttrium-86)
radioisotopes via the chelator L-NETA. Ten New Zealand white rabbits with VX2
tumor allografts were used. SW43-DOX-89Y was synthesized, loaded onto DEB (100
MUL; 100-300 MUm), and administered intra-arterially in six rabbits at increasing
doses (0.2-1.0 mg/kg). As controls, two rabbits each received either doxorubicin
IV (0.3 mg/kg) or no treatment. Consecutive serum analysis for safety and
histopathological evaluation after sacrifice were performed. One-Way ANOVA incl.
Bonferroni Post-Hoc test was performed to compare groups. Targeted compound
synthesis, loading onto DEB, and intra-arterial administration were feasible and
successful in all cases. Serum liver enzyme levels increased in a dose dependent
manner within 24 h and normalized within 3 days for 0.2/0.6 mg/kg SW43-DOX-89Y
loaded onto DEB. The two rabbits treated with 1 mg/kg SW43-DOX-89Y had to be
euthanized after 3/24 h due to worsening general condition. Histopathological
necrosis increased over time in a dose depended manner with 95-100% tumor
necrosis 3-7 days post treatment (0.6 mg/kg). SW43-DOX-89Y loaded onto DEB can be
formulated and safely administered at a concentration of 0.6 mg/kg. Loading with
radioactive isotopes (e.g., 86yttrium/90yttrium/177lutetium) to synthesize the
targeted radio-chemoembolization drug-eluting bead (TRCE-DEB) concept drug is
feasible.
PMID- 28700245
TI - Synthesis and Evaluation of Diphenyl Conjugated Imidazole Derivatives as
Potential Glutaminyl Cyclase Inhibitors for Treatment of Alzheimer's Disease.
AB - High expression of glutaminyl cyclase (QC) contributes to the initiation of
Alzheimer's disease (AD) by catalyzing the generation of neurotoxic pyroglutamate
(pE)-modified beta-amyloid (Abeta) peptides. Preventing the generation of pE
Abetas by QC inhibition has been suggested as a novel approach to a disease
modifying therapy for AD. In this work, a series of diphenyl conjugated imidazole
derivatives (DPCIs) was rationally designed and synthesized. Analogues with this
scaffold exhibited potent inhibitory activity against human QC (hQC) and good in
vitro blood-brain barrier (BBB) permeability. Further assessments corroborated
that the selected hQC inhibitor 28 inhibits the activity of hQC, dramatically
reduces the generation of pE-Abetas in cultured cells and in vivo, and improves
the behavior of AD mice.
PMID- 28700246
TI - Cross-Aldol Reaction of Activated Carbonyls with Nitrosocarbonyl Intermediates:
Stereoselective Synthesis toward alpha-Hydroxy-beta-amino Esters and Amides.
AB - A practical and flexible strategy toward alpha-hydroxy-beta-amino esters and
amides, which are important biological motifs, based on an organocatalytic cross
aldol reaction of in situ-generated nitrosocarbonyl intermediates followed by
hydrogenation is presented. The protocol features operational simplicity, high
yields, a wide substrate scope, and high regio- and diastereoselectivity
profiles. The utility of this method was showcased through the synthesis of
bestatin analogues and indole formation.
PMID- 28700247
TI - Long-Term Efficacy of Pegylated Interferon Alpha-2b in Behcet's Uveitis: A Small
Case Series.
AB - PURPOSE: To assess the long-term efficacy and safety of pegylated interferon
alpha-2b (peg-IFN-alpha-2b) for severe uveitis associated with Behcet's disease.
METHODS: Peg-IFN-alpha-2b was administrated at an initial dosage of 0,5-1,5
ug/kg/week. If any complications were observed, the dosage was tapered. Ocular
examinations, systemic findings, and treatment compliance of the patients were
evaluated. RESULTS: Control of ocular inflammation was achieved in all patients
(n = 4). The average increase in visual acuity after drug administration of 0,425
+/- 0,125 logMAR was not statistically significant (Wilcoxon Test, p = 0,066) due
to small number of cases. Any side-effects with laboratory abnormalities returned
to baseline levels with reduction of the doses. Due to less frequent injections,
increased satisfaction of the patients was noted. CONCLUSIONS: This series
highlights the peg-IFN-alpha-2b administration in Behcet's uveitis. Peg-IFN-alpha
2b has a potential long-term therapeutic effect for the treatment of severe
uveitis. Efficacy with a reduced number of injections improved the quality of
Behcet patients' lives.
PMID- 28700248
TI - Comparative Benefits and Harms of Complementary and Alternative Medicine
Therapies for Initial Treatment of Major Depressive Disorder: Systematic Review
and Meta-Analysis.
AB - OBJECTIVES: To report the comparative benefits and harms of exercise and
complementary and alternative medicine (CAM) treatments with second-generation
antidepressants (SGA) for major depressive disorder (MDD). DESIGN: Systematic
review and meta-analysis. SETTINGS: Outpatient clinics. SUBJECTS: Adults, aged 18
years and older, with MDD receiving an initial treatment attempt with SGA.
INTERVENTIONS: Any CAM or exercise intervention compared with an SGA. OUTCOME
MEASURES: Treatment response, remission, change in depression rating, adverse
events, treatment discontinuation, and treatment discontinuation due to adverse
events. RESULTS: We found 22 randomized controlled trials for direct comparisons
and 127 trials for network meta-analyses, including trials of acupuncture, omega
3 fatty acids, S-adenosyl methionine, St. John's wort, and exercise. For most
treatment comparisons, we found no differences between treatment groups for
response and remission. However, the risk of bias of these studies led us to
conclude that the strength of evidence for these findings was either low or
insufficient. The risk of treatment harms and treatment discontinuation
attributed to adverse events was higher for selective serotonin receptor
inhibitors than for St. John's wort. CONCLUSIONS: Although we found little
difference in the comparative efficacy of most CAM therapies or exercise and
SGAs, the overall poor quality of the available evidence base tempers any
conclusions that we might draw from those trials. Future trials should
incorporate patient-oriented outcomes, treatment expectancy, depressive severity,
and harms assessments into their designs; antidepressants should be administered
over their full dosage ranges; and larger trials using methods to reduce sampling
bias are needed.
PMID- 28700249
TI - Simulation-Based Evaluation of Dose-Titration Algorithms for Rapid-Acting Insulin
in Subjects with Type 2 Diabetes Mellitus Inadequately Controlled on Basal
Insulin and Oral Antihyperglycemic Medications.
AB - BACKGROUND: The purpose of this prospective, model-based simulation approach was
to evaluate the impact of various rapid-acting mealtime insulin dose-titration
algorithms on glycemic control (hemoglobin A1c [HbA1c]). METHODS: Seven stepwise,
glucose-driven insulin dose-titration algorithms were evaluated with a model
based simulation approach by using insulin lispro. Pre-meal blood glucose
readings were used to adjust insulin lispro doses. Two control dosing algorithms
were included for comparison: no insulin lispro (basal insulin+metformin only) or
insulin lispro with fixed doses without titration. RESULTS: Of the seven dosing
algorithms assessed, daily adjustment of insulin lispro dose, when glucose
targets were met at pre-breakfast, pre-lunch, and pre-dinner, sequentially,
demonstrated greater HbA1c reduction at 24 weeks, compared with the other dosing
algorithms. Hypoglycemic rates were comparable among the dosing algorithms except
for higher rates with the insulin lispro fixed-dose scenario (no titration), as
expected. The inferior HbA1c response for the "basal plus metformin only" arm
supports the additional glycemic benefit with prandial insulin lispro.
CONCLUSIONS: Our model-based simulations support a simplified dosing algorithm
that does not include carbohydrate counting, but that includes glucose targets
for daily dose adjustment to maintain glycemic control with a low risk of
hypoglycemia.
PMID- 28700250
TI - False Negative Toxoplasma Serology in an Immunocompromised Patient with PCR
Positive Ocular Toxoplasmosis.
AB - PURPOSE: The authors report a case of a 60-year-old Caucasian male with a
background of treated Chronic Lymphocytic Leukaemia (CLL) with secondary
hypogammaglobulinaemia present with toxoplasma chorioretinitis and negative serum
toxoplasma serology on presentation and on subsequent reactivation. METHODS:
Retrospective case notes review with fundal photographs. RESULTS: In this case,
on initial presentation and on recurrence, the patient's serum anti-Toxoplasma
IgG remained negative. The diagnosis was made on quantitative PCR of vitreous
initially and aqueous humor on reactivation. CONCLUSIONS: Despite negative
serology, one must still consider ocular toxoplasmosis especially in CLL patients
where the clinical picture could be compatible. Hypogammaglobulinaemia, the
inability to produce IgG antibodies, is a well-recognized complication of CLL.
Intraocular fluid sampling is essential in these cases where the sensitivity of
PCR on either aqueous or vitreous humor has been shown to be higher in
immunocompromised patients.
PMID- 28700251
TI - Choroidal and Retinal Anatomical Responses Following Systemic Corticosteroid
Therapy in Vogt-Koyanagi-Harada Disease Using Swept-Source Optical Coherence
Tomography.
AB - PURPOSE: To assess structural changes in retina and choroid after systemic
corticosteroid therapy in Vogt-Koyanagi-Harada (VKH) disease using swept-source
optical coherence tomography (SS-OCT). METHODS: SS-OCT was conducted before
treatment and during first-month follow-up in 16 eyes treated with systemic
corticosteroids for active VKH. Retina was divided into five zones depending on
pretreatment choroidal thickness (CT) of <100, >100 to <200, >200 to <300, >300
to <400 and >400MUm, and changes in retinal thickness and CT after treatment in
these zones were compared with baseline. RESULTS: Mean CT significantly improved
from 83.1+/-8.75 to 156.4+/-62.73MUm(p = 0.008) in the zone with pre-CT <100MUm
and significantly decreased from 336.1 +/- 17.28 to 266.28 +/- 81.39MUm(p =
0.008) in the zone with pre-CT > 300MUm. CONCLUSIONS: We have shown choroidal
remodeling in VKH. SS-OCT can serve as an important noninvasive tool in
assessment of treatment response in patients with VKH disease.
PMID- 28700252
TI - Modified Allogenic Simple Limbal Epithelial Transplantation Followed by
Keratoplasty as Treatment for Total Limbal Stem Cell Deficiency.
AB - PURPOSE: To describe a modified allogenic simple limbal epithelial transplant
(SLET) technique with large donor tissue explants followed by keratoplasty.
METHODS: A 69-year-old with conjunctival melanoma on her left eye developed total
limbal stem cell deficiency (LSCD) after multiple cycles of topical mitomycin.
She also had herpes stromal keratitis while on treatment with mitomycin. She
underwent modified allogenic SLET with large donor limbal tissue explants glued
on the cornea directly and the amniotic membrane placed over the limbal explants.
RESULTS: Unfortunately she had recurrence of herpes simplex keratitis that caused
worsening of stromal scarring and neovascularization. She underwent penetrating
keratoplasty to improve vision. There were no postoperative complications and the
corneal graft remains transparent 11 months after penetrating keratoplasty with
6/12 best-corrected visual acuity. CONCLUSIONS: Modified SLET with large donor
limbal explants followed by keratoplasty is an effective approach to restore
corneal transparency in cases of total LSCD.
PMID- 28700253
TI - House Dust Mite-Induced Allergic Airway Disease Is Independent of IgE and
FcepsilonRIalpha.
AB - IgE contributes to disease exacerbations but not to baseline airway
hyperresponsiveness (AHR) in human asthma. In rodent allergic airway disease
(AAD), mast cell and IgE dependence for the induction of AHR has only been
observed when mice are immunized with a relatively weak allergen without
adjuvant. To evaluate the role of IgE in murine AAD that is induced by a potent
allergen, we inoculated BALB/c and FVB/N background wild-type and IgE- or
FcepsilonRIalpha-deficient mice intratracheally with large or limiting doses of
house dust mite extract (HDM) and evaluated AHR, pulmonary eosinophilia, goblet
cell metaplasia, serum IgE, and lung mastocytosis. We found that neither IgE nor
FcepsilonRIalpha contributed to AAD, even in mice inoculated with the lowest dose
of HDM, which readily induced detectable disease, but did not increase serum IgE
or pulmonary mast cell levels. In contrast, high doses of HDM strikingly
increased serum IgE and pulmonary mast cells, although both AHR and airway mast
cell degranulation were equally elevated in wild-type and IgE-deficient mice.
Surprisingly, allergen challenge of mice with severe AAD and pulmonary
mastocytosis failed to acutely increase airway resistance, lung Newtonian
resistance, or hysteresis. Overall, this study shows that, although mice may not
reliably model acute asthma exacerbations, mechanisms that are IgE and
FcepsilonRIalpha independent are responsible for AHR and airway inflammation when
low doses of a potent allergen are inhaled repetitively.
PMID- 28700254
TI - Diquafosol Delivery from Silicone Hydrogel Contact Lenses: Improved Effect on
Tear Secretion.
AB - PURPOSE: The aim of this study was to evaluate the ability to uptake and to
deliver diquafosol from commercial contact lenses (CLs) and its effect on tear
secretion. METHODS: For both in vitro and in vivo experiments, two commercial
silicone hydrogel (Si-Hy) CLs (comfilcon A and balafilcon A) were used. The CLs
were soaked overnight for 12 h in diquafosol solution and control CLs were soaked
in saline solution (NaCl 0.9%). The CLs were introduced into a new well container
with 1 mL of saline solution, and aliquots of 100 MUL were extracted at different
times during a period of 6 h to measure the diquafosol release. For in vivo
experiments, nine male New Zealand white rabbits were used. CLs soaked in
diquafosol were inserted in the eye and compared with control CLs and diquafosol
topical instillation. Schirmer's tests were performed to evaluate tear secretion
and diquafosol release at different times during the 6-h period. RESULTS: For in
vitro experiments, the largest amount of diquafosol was released during the first
24 h for both CL materials under study, without statistical differences between
them (P < 0.05). The topical application showed the maximum release at 1 min
after instillation, meanwhile the release from both CL materials was at 30 min of
insertion. The effect on tear secretion was higher with CL delivery compared with
topical instillation (P < 0.05), being 300 min for both CLs and 90 min for
topical application. CONCLUSION: The use of CLs increases the residence time of
diquafosol on the ocular surface with a concomitant enhancement in tear secretion
during longer periods.
PMID- 28700255
TI - Disease Progression in Idiopathic Pulmonary Fibrosis. FVC Is Not Enough.
PMID- 28700257
TI - Orbital basal cell adenoma: A case report.
AB - Basal cell adenomas are uncommon benign epithelial tumors of the salivary gland.
Orbital basal cell adenoma of the orbit has not been described before. The
authors report an unusual case of basal cell adenoma that presented in the orbit.
Immunohistochemical findings for the tumor are also described.
PMID- 28700256
TI - Hippo Pathway: An Emerging Regulator of Craniofacial and Dental Development.
AB - The evolutionarily conserved Hippo signaling pathway is a vital regulator of
organ size that fine-tunes cell proliferation, apoptosis, and differentiation. A
number of important studies have revealed critical roles of Hippo signaling and
its effectors Yap (Yes-associated protein) and Taz (transcriptional coactivator
with PDZ binding motif) in tissue development, homeostasis, and regeneration, as
well as in tumorigenesis. In addition, recent studies have shown evidence of
crosstalk between the Hippo pathway and other key signaling pathways, such as Wnt
signaling, that not only regulates developmental processes but also contributes
to disease pathogenesis. In this review, we summarize the major discoveries in
the field of Hippo signaling and what has been learned about its regulation and
crosstalk with other signaling pathways, with a particular focus on recent
findings involving the Hippo-Yap pathway in craniofacial and tooth development.
New and exciting studies of the Hippo pathway are anticipated that will
significantly improve our understanding of the molecular mechanisms of human
craniofacial and tooth development and disease and will ultimately lead to the
development of new therapies.
PMID- 28700258
TI - Progressive orbital granular cell tumour associated with medial rectus.
AB - Granular cell tumour is a rare soft tissue tumour that can occur in any part of
the body, but seldom in ocular adnexa. It usually behaves in a benign fashion. We
report a case of a 54-year-old man with a well-demarcated, solitary, slow-growing
orbital tumour which lead to significant ocular symptoms. The case was a
diagnostic and therapeutic challenge due to its location and difficulty in
obtaining tissue for a histological diagnosis. Surgical biopsy attempts were made
but they all failed to uncover the true identity of the lesion. A definitive
diagnosis was revealed with complete surgical excision of the tumour, which was
challenging due to its size and close association with rectus muscle. This case
has highlighted that orbital granular cell tumour may result in significant
ocular symptoms. Adequate exposure to the anatomical site is the key to obtaining
diagnosis and complete excision of a lesion.
PMID- 28700259
TI - Mixed Method Study to Investigate Models of Australian Integrative Oncology.
AB - OBJECTIVES: This study explored the models of services and experiences of
coordinators and directors engaged in providing complementary and alternative
medicine (CAM) or integrative medicine (IM) in oncology centers throughout
Australia. DESIGN: Fourteen leaders of IM programs from ten systematically
selected Australian oncology centers were interviewed. Participants described
their center's service model. Interview transcripts were thematically analyzed to
identify underlying themes. Results were merged using the matrix technique for
triangulation. RESULTS: Ten oncology centers were reviewed. IM was perceived in
the context of supportive care and wellness. IM program types provided included
the following: body-mind programs (56%); body-energy programs (23%), and body
programs (21%). All programs were outpatient focused, generally did not require a
doctors' referral, were freely accessible to cancer patients and carers at no or
minimal cost, were centralized by coordinators, and involved volunteers, nurses,
allied health practitioners, third parties, and patients in their treatment
planning. Interaction between medical and CAM/IM teams was limited and tended to
be informal. The underlying structure comprised four main themes: cultural
context, human components, systematic components, and resource availability.
Human components and resources were considered important in influencing cultural
context and systematic components in the IM structure. CONCLUSION: Australian
integrative oncology models are based on the concept of wellness and
individualized care, focused on patient empowerment and engagement. IM models are
generally independent of conventional medical care. Building relationships and
trust between stakeholders and open collaboration with conventional medical care
will be important to integrate IM into the hospital system. Systemic changes to
deliver patient centered care in the provision of IM healthcare will facilitate
the incorporation of CAM and IM into cancer services in hospital settings.
PMID- 28700260
TI - A perspective on the challenges and issues in developing biomarkers for human
allergic risk assessments.
PMID- 28700261
TI - Orbital implant infection by Corynebacterium amycolatum.
AB - Corynebacterium amycolatum is a saprophyte gram-positive bacillus of the skin
flora. It has been linked to diverse infections in immunocompromised patients and
also of different types of prostheses. However, to our knowledge, there are no
reports on its ability to produce ocular infections or to grow over alloplastic
materials for orbital surgery. We present a case of orbital implant exposure
including pure isolation of C. amycolatum. The patient was referred for discharge
in his socket. After removal of the artificial eye, a large area of implant
exposure and signs of chronic infection were observed. A microbiological sample
was taken by rubbing the implant with a sterile swab. The sample was cultured and
C. amycolatum was identified by phenotypical characterization. Other microbial
species were not isolated. Besides being able to adhere to cardiac and joint
devices, this case shows that C. amycolatum is a potential infectious agent of
orbital prostheses. Pure isolation of C. amycolatum in an ocular sample is
extremely rare and suggests an etiological role of this microorganism in an
ocular or periocular infection.
PMID- 28700262
TI - The sixth sensor: A Candida albicans biofilm master regulator that responds to
inter-kingdom interactions.
PMID- 28700263
TI - Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer.
PMID- 28700264
TI - Overall effectiveness of pneumococcal conjugate vaccines: An economic analysis of
PHiD-CV and PCV-13 in the immunization of infants in Italy.
AB - Pneumococcal diseases are associated with a significant clinical and economic
burden. The 7-valent pneumococcal conjugate vaccine (PCV-7) has been used for the
immunization of newborns against invasive pneumococcal diseases (IPD) in Italy
while now, the pneumococcal non-typeable Haemophilus influenzae protein D
conjugate vaccine (PHiD-CV) and the 13-valent pneumococcal conjugate vaccine (PCV
13) are available. The aim of this analysis was to compare the estimated health
benefits, cost and cost-effectiveness of immunization strategies vs. non
vaccination in Italy using the concept of overall vaccine effectiveness. A
published Markov model was adapted using local data wherever available to compare
the impact of neonatal pneumococcal vaccination on epidemiological and economic
burden of invasive and non-invasive pneumococcal diseases, within a cohort of
newborns from the Italian National Health Service (NHS) perspective. A 18-year
and a 5-year time horizon were considered for the base-case and scenario
analysis, respectively. PHiD-CV and PCV-13 are associated with the most important
reduction of the clinical burden, with a potential marginal advantage of PHiD-CV
over PCV-13. Compared with no vaccination, PHiD-CV is found on the higher limit
of the usually indicated willingness to pay range (30,000 - 50,000?/quality
adjusted life year [QALY] gained), while the incremental cost-effectiveness ratio
(ICER) for PCV-13 is slightly above. Compared with PCV-13, PHiD-CV would provide
better health outcomes and reduce costs even at parity price, solely due to its
differential effect on the incidence of NTHi acute otitis media (AOM). The
analysis on a shorter time horizon confirms the direction of the base-case.
PMID- 28700265
TI - Safety and immunogenicity of a quadrivalent influenza vaccine in adults 65 y of
age and older.
AB - Frequent mismatches between the predominant circulating B strain lineage and the
B strain lineage in trivalent influenza vaccines have resulted in missed
opportunities to prevent influenza illness. Quadrivalent influenza vaccines
containing B strains from each of the 2 lineages have been developed for improved
prevention of influenza B infections. Here, we describe the results of a phase
III, randomized, double-blind, active-controlled, multicenter trial examining the
safety and immunogenicity of a split-virion inactivated quadrivalent influenza
vaccine (IIV4) in 675 adults >= 65 y of age (NCT01218646). Participants were
randomly assigned 1:1:1 to receive a single intramuscular injection with the
investigational IIV4, or one of 2 split-virion trivalent inactivated influenza
vaccines (IIV3s): a licensed IIV3 containing a B Victoria-lineage strain or an
investigational IIV3 containing a B Yamagata-lineage strain. Post-vaccination
(day 21) hemagglutinin inhibition titers to all strains induced by IIV4 were
statistically non-inferior to those induced by the 2 IIV3s. In addition, for each
B strain, rates of seroconversion in the IIV4 group were superior to those
induced by the comparator IIV3 not containing that B strain. For all vaccines,
the most common solicited reaction was injection-site pain, and most reactions
were mild to moderate in intensity and transient. Overall safety profiles were
similar between IIV4 and the IIV3s, and no vaccine-related serious adverse events
were reported. These results confirm that in adults >= 65 y of age, IIV4 was well
tolerated and immunogenic against the additional B lineage strain without
compromising the immunogenicity of the other 3 vaccine strains.
PMID- 28700266
TI - Resources for the Provision of Nutrition Support to Children in Educational
Environments.
AB - The use of nutrition support outside of institutional settings has contributed to
maintaining the health, well-being, and nutrition status of many medically
complex children. As these children grow and enter educational settings, there is
a need for awareness of the care that these children require for nutrition
support therapy. This document is designed to raise awareness to these needs,
provide best practice educational resources for those involved in the supervision
or provision of nutrition support to children in an educational environment, and
promote safe and effective care. Care of children requiring nutrition support is
an ongoing and shared partnership among the educational team, medical team,
homecare team, and parents/caregivers. Care is individualized to the specific
child and may include provision of nutrition support therapy while in the school
setting, maintenance of a nutrition access device, and monitoring to safely
prevent or act on signs of potential complications. Suggested roles and
responsibilities of those involved with nutrition support care are discussed;
however, all interventions and routine care must be in accordance with
physician's orders, school nurse privileges and competencies, and state and local
regulations.
PMID- 28700267
TI - The Mismeasurement of Mind: Life-Span Changes in Paired-Associate-Learning Scores
Reflect the "Cost" of Learning, Not Cognitive Decline.
AB - The age-related declines observed in scores on paired-associate-learning (PAL)
tests are widely taken as support for the idea that human cognitive capacities
decline across the life span. In a computational simulation, we showed that the
patterns of change in PAL scores are actually predicted by the models that
formalize the associative learning process in other areas of behavioral and
neuroscientific research. These models also predict that manipulating language
exposure can reproduce the experience-related performance differences erroneously
attributed to age-related decline in age-matched adults. Consistent with this,
results showed that older bilinguals outperformed native speakers in a German PAL
test, an advantage that increased with age. These analyses and results show that
age-related PAL performance changes reflect the predictable effects of learning
on the associability of test items, and indicate that failing to control for
these effects is distorting the understanding of cognitive and brain development
in adulthood.
PMID- 28700268
TI - US healthcare costs attributable to type A and type B influenza.
AB - While the overall healthcare burden of seasonal influenza in the United States
(US) has been well characterized, the proportion of influenza burden attributable
to type A and type B illness warrants further elucidation. The aim of this study
was to estimate numbers of healthcare encounters and healthcare costs
attributable to influenza viral strains A and B in the US during the 2001/2002 -
2008/2009 seasons. Healthcare encounters and costs in the US during the 2001/2002
- 2008/2009 seasons for influenza type A and influenza type B were estimated
separately and collectively, by season and age group, based on data from
published literature and secondary sources for: rates of influenza-related
encounters requiring formal healthcare, unit costs of influenza-related
healthcare encounters, and estimates of population size. Across 8 seasons,
projected annual numbers of influenza-related healthcare encounters ranged from
11.3-25.6 million, and healthcare costs, from $2.0-$5.8 billion. While the
majority of influenza illness was attributable to type A strains, type B strains
accounted for 37% of healthcare costs across all seasons, and as much as 66% in a
single season. The outpatient burden of type B disease was considerable among
persons aged 18-64 y while the hospital cost burden was highest in young
children. Influenza viral strain B was associated with considerable health system
burden each year during the period of interest. Increasing influenza vaccine
coverage, especially with the recently approved quadrivalent products including
an additional type B strain, could potentially reduce overall annual influenza
burden in the US.
PMID- 28700269
TI - Threats to Information Security - Public Health Implications.
PMID- 28700270
TI - H2Mab-77 is a Sensitive and Specific Anti-HER2 Monoclonal Antibody Against Breast
Cancer.
AB - Human epidermal growth factor receptor 2 (HER2) plays a critical role in the
progression of breast cancers, and HER2 overexpression is associated with poor
clinical outcomes. Trastuzumab is an anti-HER2 humanized antibody that leads to
significant survival benefits in patients with HER2-positive metastatic breast
cancers. In this study, we developed novel anti-HER2 monoclonal antibodies (mAbs)
and characterized their efficacy in flow cytometry, Western blot, and
immunohistochemical analyses. Initially, we expressed the full length or
ectodomain of HER2 in LN229 glioblastoma cells and then immunized mice with
ectodomain of HER2 or LN229/HER2, and performed the first screening by enzyme
linked immunosorbent assays using ectodomain of HER2. Subsequently, we selected
mAbs according to their efficacy in flow cytometry (second screening), Western
blot (third screening), and immunohistochemical analyses (fourth screening).
Among 100 mAb clones, only three mAbs reacted with HER2 in Western blot, and
clone H2Mab-77 (IgG1, kappa) was selected. Finally, immunohistochemical analyses
with H2Mab-77 showed sensitive and specific reactions against breast cancer
cells, warranting the use of H2Mab-77 to detect HER2 in pathological analyses of
breast cancers.
PMID- 28700271
TI - Lsd1, a metabolic sensor of environment requirements that prevents adipose tissue
from aging.
AB - Understanding development and maintenance of beige adipocytes provide exciting
insights in establishing novel therapies against obesity and obesity-associated
disorders. Lysine-specific demethylase 1 (Lsd1) is an epigenetic eraser required
for differentiation and function of adipocytes. Lsd1 is involved in early
commitment of preadipocytes, but dispensable for terminal differentiation of
white adipose tissue (WAT). In mature adipocytes, Lsd1 responds to different
environmental stimuli to alter metabolic function and enable proper thermogenic
and oxidative response. Exposure to cold leads to Lsd1 upregulation and
subsequent beiging of WAT. Oppositely, Lsd1 levels decline during aging resulting
in a conversion of beige into white adipocytes, associated with loss of
thermogenic properties of WAT. Lsd1 maintains beige adipocytes by controlling the
expression of the nuclear receptor peroxisome proliferator-activated receptor
alpha. In summary, our studies not only provided insights into the mechanism of
age-related beige-to-white adipocyte transition, but also established Lsd1 as a
sensor that enables thermogenic response in WAT.
PMID- 28700273
TI - PIK3CA oncogenic mutations in neoadjuvant treatments for breast cancer.
PMID- 28700272
TI - Accuracy of a Fourth-Generation Subcutaneous Continuous Glucose Sensor.
AB - BACKGROUND: This study evaluated the accuracy and performance of a fourth
generation subcutaneous glucose sensor (GuardianTM Sensor 3) in the abdomen and
arm. METHODS: Eighty-eight subjects (14-75 years of age, mean +/- standard
deviation [SD] of 42.0 +/- 19.1 years) with type 1 or type 2 diabetes
participated in the study. Subjects wore two sensors in the abdomen that were
paired with either a MiniMedTM 640G insulin pump, or an iPhone(r) or iPod(r)
touch(r) running a glucose monitoring mobile application (Guardian Connect
system) and a third sensor in the arm, which was connected to a glucose sensor
recorder (GSR). Subjects were also asked to undergo in-clinic visits of 12-14 h
on study days 1, 3, and 7 for frequent blood glucose sample testing using a
Yellow Springs Instrument (YSI) reference. RESULTS: The overall mean absolute
relative difference (MARD +/- SD) between abdomen sensor glucose (SG) and YSI
reference values was 9.6% +/- 9.0% and 9.4% +/- 9.8% for the MiniMed 640G insulin
pump and Guardian Connect system, respectively; and 8.7% +/- 8.0% between arm SG
and YSI reference values. The percentage of SG values within 20% agreement of the
YSI reference value (for YSI >80 mg/dL) was 90.7% with the MiniMed 640G insulin
pump, 91.8% with the Guardian Connect system, and 93.1% for GSR-connected arm
sensors. Mean functional sensor life, when calibrating 3-4 times/day, was 145.9
+/- 39.3 h for sensors paired with the MiniMed 640G insulin pump, 146.1 +/- 41.6
h for sensors paired with the Guardian Connect system, and 147.6 +/- 40.4 h for
sensors connected to the GSR. Responses to survey questions regarding sensor
comfort and ease of use were favorable. CONCLUSIONS: The Guardian Sensor 3
glucose sensor, whether located in abdomen or the arm, provided accurate glucose
readings when compared with the YSI reference and demonstrated functional life
commensurate with the intended 7-day use. ClinicalTrials.gov : NCT02246582.
PMID- 28700274
TI - Systematic Review and Network Meta-Analysis of Treatment Outcomes for Multiple
Myeloma.
PMID- 28700275
TI - Guideline-Based Statin Eligibility, Cancer Events, and Noncardiovascular
Mortality in the Framingham Heart Study.
AB - Purpose Cancer and cardiovascular disease share risk factors, and there is some
evidence that statins reduce cancer mortality. We sought to determine the
accuracy of the 2013 American College of Cardiology/American Heart Association
statin eligibility criteria to identify individuals at a higher risk of
developing cancer or of dying as a result of cancer or other noncardiovascular
causes. Methods We included 2,196 participants (50.5 +/- 8.1 years of age; 55%
female) who were statin naive and free of cancer at baseline from the offspring
and third-generation cohorts of the community-based longitudinal Framingham Heart
Study. Statin eligibility was determined per American College of
Cardiology/American Heart Association guidelines, and subclinical coronary
atherosclerosis was assessed by computed tomography. The primary outcome was
incident cancer at a median of 10.0 years (interquartile range, 9.1-10.6 years)
of follow-up, and secondary outcomes were cancer mortality and noncardiovascular
mortality. Results The incident cancer rate was 11.2% (247 of 2,196), with 58
noncardiovascular deaths, including 39 cancer deaths (1.8%). Overall, 37% (812 of
2,196) were statin eligible. Incident cancer occurred in 125 (15%) of the 812
statin-eligible participants versus 122 (8.8%) of the 1,384 of noneligible
participants (subdistribution hazard ratio [SDHR], 1.8 [1.4 to 2.3]; P < .001).
Cancer mortality occurred in 34 (4.2%) of the 812 statin-eligible participants
versus five (0.4%) of the 1,384 noneligible participants (SDHR, 12.1 [4.7 to 31];
P < .001). Noncardiovascular mortality occurred in 49 (6.0%) of the 812 statin
eligible participants versus nine (0.7%) of the 1,384 noneligible participants
(SDHR, 10.1 [5.0 to 21]; P < .001). In stratified analyses, these findings were
independent of any individual causative risk factor such as body mass index, age,
or smoking status. Conclusion In this community-based primary prevention cohort,
guideline-based statin eligibility accurately identified patients at a higher
risk of developing cancer and cancer-related mortality. Shared risk profiles and
potential benefits of statins between cancer and cardiovascular outcomes may
provide a unique opportunity to improve population health.
PMID- 28700276
TI - Patient Preferences for Primary Care Provider Roles in Breast Cancer Survivorship
Care.
AB - Purpose Prior studies have suggested a need for greater clarity about provider
roles in team-based cancer care; however, little is known about patients'
preferences regarding which providers handle their care needs after primary
cancer treatment. Methods We surveyed women with newly diagnosed stages 0 to II
breast cancer who were treated in 2014 and 2015 as reported to the Georgia and
Los Angeles SEER registries (N = 2,372; 68% response rate). Patient preferences
regarding which provider handles the following care needs after treatment were
ascertained: follow-up mammograms, screening for other cancers, general
preventive care, and comorbidity management. Associations between patient
demographic factors with preferences for provider roles-oncology-directed care
versus primary care provider (PCP)-directed care-were assessed by using
multivariable logistic regression. Results The majority of women preferred that
their PCPs handle general preventive care (79%) and comorbidity care (84%), but a
notable minority of women preferred that their oncologists direct this care (21%
and 16%, respectively). Minority women-black and Asian versus white-and women
with a high school education or less-versus undergraduate college education or
more-displayed greater odds of preferring oncology-directed care-versus PCP
directed care-for their general preventive care (black odds ratio [OR], 2.01; 95%
CI, 1.43 to 2.82; Asian OR, 1.74; 95% CI, 1.13 to 2.69; high school education or
less OR, 1.51; 95% CI, 1.10 to 2.08). Similar variations existed for comorbidity
care. Conclusion In this sample, minority women and those with less education
more often preferred that oncologists direct certain aspects of their care after
breast cancer treatment that are normally delivered by a PCP. Efforts to clarify
provider roles in survivorship care to patients may be effective in improving
team-based cancer care.
PMID- 28700278
TI - In Accordance With Our Best Estimates.
PMID- 28700277
TI - Pediatric Palliative Oncology: Bridging Silos of Care Through an Embedded Model.
PMID- 28700279
TI - Reply to X. Armoiry et al.
PMID- 28700280
TI - Biologic Treatment Options for Retinal Neovascularization in Behcet's Disease.
AB - PURPOSE: Relapsing ocular inflammation occurs in about 70% of patients with
Behcet's disease (BD) and can lead to permanent loss of vision.
Neovascularization of the optic disc (NVD) or elsewhere in the retina (NVE) is a
relatively uncommon but severe complication that lacks standardized treatment.
METHODS: We report on the therapeutic use of anti-TNF monoclonal antibodies for
BD-associated NVD and NVE in one pediatric patient (subcutaneous adalimumab) and
one young man (intravenous infliximab). Also, we review the previously published
experience on biologic therapeutic options, namely anti-TNF agents and interferon
alpha in a total of three and eight patients, respectively. RESULTS: A fast-onset
therapeutic effect was observed in both patients leading to complete regression
of neovascularizations. CONCLUSIONS: Both options may lead to regression of
neovascularization, thus preventing loss of vision, but comparative studies need
to determine the optimal treatment for this sight-threatening complication of BD.
PMID- 28700281
TI - Eyebrow reconstruction.
AB - This is a systematic review of eyebrow reconstruction options, using the PubMed
database, as well as dermatology and plastic surgery texts. Eyebrow
reconstruction options in various clinical scenarios (small, large, medial,
lateral, and total defects) are presented. The goals of eyebrow reconstruction
are to provide structural, functional, and aesthetic restoration. A good
understanding of various eyebrow reconstruction techniques is essential for
plastic, dermatologic, and oculoplastic surgeons.
PMID- 28700283
TI - Update on Immunological Test (Quantiferon-TB Gold) Contribution in the Management
of Tuberculosis-Related Ocular Inflammation.
AB - PURPOSE: To clarify interferon-gamma release assay (IGRA) contributions to
intraocular tuberculosis management, according to related TB endemic prevalence.
METHODS: Despite extensive investigations, including IGRA, the diagnosis of
intraocular tuberculosis (TB) is still challenging and remains mostly
presumptive. According to the literature, it appears that management of suspected
ocular TB differs significantly based on whether patients are from areas of high
TB prevalence or from non-TB-endemic countries. The accuracy and final
contribution of chest X-rays, tuberculin skin test and IGRA differ significantly
according to low or high endemic TB areas. This work aims to review IGRA test
outcomes in the light of these clinical and epidemiological settings. We
therefore focused our analysis and its subsequent guidelines proposal based on
the TB prevalence where the patient lives. CONCLUSION: We believe that distinct
guidelines should be determined for managing patients with suspected ocular TB,
first taking into consideration the relative TB prevalence.
PMID- 28700285
TI - Krieger Responds.
PMID- 28700282
TI - A randomized, open-label clinical trial to evaluate immunogenicity and safety of
an indigenously developed DTwP-Hib tetravalent combination vaccine (Easyfour(r)
TT) with Quadrovax(r) in Indian infants.
AB - : An open-label, randomized, multi-center trial was conducted to compare the
immunogenicity and safety of an indigenously developed tetravalent DTwP-Hib
vaccine, Easyfour(r)-TT with a commercially available vaccine, Quadrovax(r). A
total of 244 infants in good health, aged 6-10 weeks, were randomized in a 1:1
allocation to receive three doses of the test or comparator vaccine.
Immunogenicity of the vaccines was determined by measuring the baseline and post
vaccination antibody response against the vaccine antigens; safety was evaluated
in terms of local and systemic reactions (solicited and unsolicited) reported
during the trial. Similar levels of seroprotection/seroresponse were achieved, 4
weeks after receiving 3 doses of Easyfour(r)-TT and Quadrovax(r), and the
antibody response of Easyfour(r)-TT was found non-inferior to Quadrovax(r),
against all four vaccine antigens. Both vaccines were well tolerated and had
similar reactogenicity profiles, with a significantly lower occurrence of local
(redness at injection site) and systemic reactions (irritability post
vaccination) with Easyfour(r)-TT vaccine as compared to Quadrovax(r) (p < 0.05).
All adverse events resolved completely with no sequelae. All through the study,
only one serious adverse event was observed that completely resolved upon
treatment and was deemed unrelated to the vaccine administered. This study
demonstrated that Easyfour(r)-TT vaccine was safe and immunogenic. CLINICAL TRIAL
REGISTRATION NUMBER: CTRI/2014/12/005326 (registered with the Clinical Trial
Registry of India (CTRI)).
PMID- 28700287
TI - All Models Are Wrong; Some Are Useful.
PMID- 28700286
TI - Activism Combatting AIDS.
PMID- 28700288
TI - Anestis et al. Respond.
PMID- 28700289
TI - Differing Perspectives on Analyzing Data Related to Firearms and Suicide.
PMID- 28700291
TI - Defining Roles for Schools and Programs of Public Health in the Age of Trump.
PMID- 28700292
TI - Trump Order Mandating Deportation for Health Service Use: Not Legally Sufficient.
PMID- 28700293
TI - Underuse of Chest Radiography Versus Computed Tomography for Lung Cancer
Screening.
PMID- 28700294
TI - Accountable Care Organizations' Payments to Physicians: Patients Should Have the
Right to Know.
PMID- 28700295
TI - Reasons for Caution When Emphasizing Health Disparities for Sexual and Gender
Minority Adults in Public Health Campaigns.
PMID- 28700296
TI - Princess Diana and Reduced Traffic Deaths in France and the United States.
PMID- 28700297
TI - AJPH Global News.
PMID- 28700298
TI - Raising Our Voices Against Discrimination-and for Public Health.
PMID- 28700300
TI - Repealing the Affordable Care Act Essential Health Benefits: Threats and
Obstacles.
PMID- 28700299
TI - Chronic Health Conditions and Key Health Indicators Among Lesbian, Gay, and
Bisexual Older US Adults, 2013-2014.
AB - OBJECTIVES: To examine disparities in chronic conditions and health indicators
among lesbian, gay, and bisexual (LGB) adults aged 50 years or older in the
United States. METHODS: We used data from the 2013 and 2014 National Health
Interview Survey to compare disparities in chronic conditions, health outcomes
and behaviors, health care access, and preventive health care by sexual
orientation and gender. RESULTS: LGB older adults were significantly more likely
than heterosexual older adults to have a weakened immune system and low back or
neck pain. In addition, sexual minority older women were more likely than their
heterosexual counterparts to report having arthritis, asthma, a heart attack, a
stroke, a higher number of chronic conditions, and poor general health. Sexual
minority older men were more likely to report having angina pectoris or cancer.
Rates of disability and mental distress were higher among LGB older adults.
CONCLUSIONS: At substantial cost to society, many disparities in chronic
conditions, disability, and mental distress observed in younger LGB adults
persist, whereas others, such as cardiovascular disease risks, present in later
life. Interventions are needed to maximize LGB health.
PMID- 28700301
TI - A Public Health of Consequence: Review of the August 2017 Issue of AJPH.
PMID- 28700302
TI - A Platform to Launch a Collective Discussion About Reforming US Health Politics
and Policy.
PMID- 28700303
TI - The Pursuit of Inclusive Prosperity, Universal Health Care, and Stronger
Democracy.
PMID- 28700304
TI - Ideologically Motivated Violence: A Public Health Approach to Prevention.
PMID- 28700305
TI - The Opioid Crisis and the Need for Compassion in Pain Management.
PMID- 28700306
TI - How Can Helicopter Parents Have Missed Young Worker Safety?
PMID- 28700307
TI - Alang et al. Respond.
PMID- 28700308
TI - Toward a Constructive Public Health Agenda on Race and Police Use of Force.
PMID- 28700311
TI - Prepare and Support Our Chief Health Strategists on the Front Lines.
PMID- 28700309
TI - Spitzer et al. Respond.
PMID- 28700312
TI - Exchanging Identifiable Health Information Among Health Departments: A Route
Through the Legal Maze.
PMID- 28700315
TI - Serious, Nonlethal Firearm-Related Injuries in the United States: Compiling the
Evidence.
PMID- 28700316
TI - Public Health Without Fear of Consequences or Inconsequences.
PMID- 28700317
TI - Utility and development of microfluidic platforms for platelet research.
PMID- 28700318
TI - The Challenge of Postpartum Weight Loss in Low-Income Mothers.
PMID- 28700319
TI - Adamts1 responds to systemic cues and gates adipogenesis.
AB - Intuitively, excess caloric intake causes adipose tissue expansion. However, the
signals and mechanisms by which this systemic trigger directs a local response in
the adipose tissue are incompletely understood. Both hypertrophy of existing
adipocytes and the generation of new adipocytes through differentiation of
adipocyte precursor cells (APCs), contribute to adipose tissue expansion in
response to changes in the diet. Ex vivo studies of this process elucidated an
elegant network of mostly transcription factors that drive APCs through the
differentiation (adipogenesis) process. Here we discuss our study that identified
an Adamts1 signal as a glucocorticoid and diet responsive regulator of an
extracellular relay system that modulates the initiation of this intracellular
adipogenesis program in APCs. Furthermore, we describe how we applied sensitive
tools that enable monitoring of endogenous APC activity to study the early
response to high-fat diet in vivo.
PMID- 28700320
TI - Problems in the Protection of Reintroduced Przewalski's Horses (Equus ferus
przewalskii) Caused by Piroplasmosis.
AB - The objectives of our research on equine piroplasmosis were to clarify the
prevalence of the piroplasms Babesia caballi and Theileria equi among
reintroduced Przewalski's horses (takhi, Equus ferus przewalskii) in comparison
with horses (Equus caballus) of nomads from around Hustai National Park in
Mongolia and to determine the mortality among takhi during 2012 to 2015. The
prevalence of T. equi was high in 2014 at 80% among nomadic horses and 84% among
takhi. We found no evidence of B. caballi infection among takhi. A homology
comparison of the 18S rRNA base sequence of T. equi showed the same sequence in
both domestic horses and takhi. According to the national park records,
piroplasmosis is a cause of high mortality in young takhi (19%). The results
suggested that takhi were infected with T. equi in this park, and the infection
is an important issue when reintroducing the takhi into the wild and increasing
the numbers of the animals in nature. Continuous monitoring and vector control
were noted as important issues in future conservation programs.
PMID- 28700321
TI - Tyzzer's Disease in Free-Ranging Passerine Birds in California, USA.
AB - Tyzzer's disease was diagnosed as the cause of mortality in free-ranging hatch
year passerine birds in Southern California, US. Birds presented with ataxia,
tremors, and opisthotonos and died or were euthanized. Postmortem examination of
four birds identified encephalitis on microscopy with characteristic stacked,
slender bacterial rods visible with special stains. Infection with Clostridium
piliforme was confirmed by real-time PCR.
PMID- 28700322
TI - MOLECULAR EPIDEMIOLOGY OF AVIAN POXVIRUS IN THE ORIENTAL TURTLE DOVE
(STREPTOPELIA ORIENTALIS) AND THE BITING MIDGE (CULICOIDES ARAKAWAE) IN THE
REPUBLIC OF KOREA.
AB - A total of 600 wild birds were analyzed for the causes of mortality in the
Republic of Korea (ROK) from 2011 to 2013. Avian poxvirus (APV) infections were
identified as the primary cause of mortality in 39% (29/74) Oriental Turtle Doves
(Streptopelia orientalis). At necropsy, all 29 S. orientalis birds, of which, 76%
(22/29) were juveniles, had severe diphtheritic lesions in their oral and nasal
cavities and on their eyelids, which were the lesions of APV that resulted in
mortality. We detected APV infection by chorioallantoic membrane inoculation and
molecular study of the partial region of the P4b gene. All isolates belonged to
the same APV strain and were identical to strains isolated from several different
pigeon species in South Africa. Phylogenetically, the APV strain identified in S.
orientalis belonged to subclade A2, which includes isolates from several species
of pigeons from different parts of the world, including the United Kingdom,
Germany, India, Egypt, Hawaii, Georgia, Hungary, South Africa, Tanzania, and the
ROK. This identity indicated that this diphtheritic APV strain may be a potential
pathogen of other pigeon species in the ROK and neighboring countries throughout
the range of S. orientalis. However, reticuloendotheliosis virus insertion into
the APV genome was not detected by PCR in any of the 29 APV infections. An
identical strain of APV observed in S. orientalis was also detected in Culicoides
arakawae (biting midge), with annual peak populations corresponding to the
presence of APV in S. orientalis. Culicoides arakawae may be a primary vector of
APV in S. orientalis. Active surveillance of APVs in wild birds and C. arakawae
is needed to better understand the epidemiology of APVs, host-vector
relationships, and its ecological effects on S. orientalis in the ROK.
PMID- 28700323
TI - Baylisascaris schroederi Infection in Giant Pandas (Ailuropoda melanoleuca) in
Foping National Nature Reserve, China.
AB - The giant panda (Ailuropoda melanoleuca) is the most iconic endangered species in
the world, but there is little information about the spatial and temporal
distribution of parasites in the wild giant panda population. In total, 193 fecal
samples from giant pandas in the Foping National Nature Reserve, People's
Republic of China, were analyzed for parasite eggs using a modification of the
McMaster technique. The morphology and size of Baylisascaris schroederi eggs were
observed under an optical microscope. The prevalence and intensity of B.
schroederi infection during the sampling year 2012 were 52.3% (101/193) and 89
eggs/g of feces, respectively, among giant pandas in this population. The
prevalence of B. schroederi in the pandas varied during different months of the
year, from 7% to 100%, and the prevalences in spring, summer, autumn, and winter
were 71, 77, 23, and 18%, respectively. The prevalence was not significantly
different between giant pandas that ate two different types of bamboo, but the
intensity of infection was higher in the group eating Arundinaria fargesii
(P=0.043). Altitude, temperature, and dew point were correlated with the
infection intensity (r=-0.224, P<0.001; r=0.328, P<0.001; r=0.328, P=0.028,
respectively). There was no correlation between infection intensity and distance
to rivers. This study provides a better understanding of B. schroederi prevalence
among the wild giant pandas in Foping National Nature, China.
PMID- 28700324
TI - Usability and acceptability by a younger and older user group regarding a mobile
robot-supported gait rehabilitation system.
AB - The aim of the study was to identify differences regarding usability,
acceptability, and barriers of usage of a robot-supported gait rehabilitation
system between a younger and older group of patients with gait impairments. A
mobile robot-supported gait rehabilitation prototype was tested on a group of
geriatric patients aged 60 and above, and on a group of young patients aged 59
and below in a clinical setting during five therapy sessions. The involved
therapists received 2 days training with the system and could test it profoundly.
Data on usability, acceptability, and barriers to system usage were collected
with questionnaires and structured interviews with the patients. The robotic
system received overall moderate usability and good acceptability ratings; it was
rated as clearly structured, practical, and safe. Analyses identified a few
barriers, such as time-intensive setup of the system or tight leg shells, which
can be minimized with regular training and system adaptations. Differences
between the two user groups could be revealed and will be used for future
investigation. This study showed the potential of the mobile robot-supported
system for gait rehabilitation, but also pointed out further need for action.
Efficacy studies are the next step in the evaluation process.
PMID- 28700360
TI - Stigma and substance use disorders: an international phenomenon.
AB - PURPOSE OF REVIEW: To collect and update published information on the stigma
associated with substance abuse in nonclinical samples, which has not been
recently reviewed. RECENT FINDINGS: Searching large databases, a total of only 17
articles were published since 1999, with the majority of studies conducted
outside the United States. Using major stigma concepts from a sociological
framework (stereotyping, devaluation in terms of status loss, discrimination, and
negative emotional reactions), the studies reviewed predominantly indicated that
the public holds very stigmatized views toward individuals with substance use
disorders (SUDs), and that the level of stigma was higher toward individuals with
SUDs than toward those with other psychiatric disorders. SUMMARY: The prevalence
of SUDs is increasing in the US general population, but these disorders remain
seriously undertreated. Stigma can reduce willingness of policymakers to allocate
resources, reduce willingness of providers in nonspecialty settings to screen for
and address substance abuse problems, and may limit willingness of individuals
with such problems to seek treatment. All of these factors may help explain why
so few individuals with SUDs receive treatment. Public education that reduces
stigma and provides information about treatment is needed.
PMID- 28700361
TI - Persistent pain in cancer survivors.
AB - PURPOSE OF REVIEW: As people are living longer after a diagnosis and primary
treatment for cancer, or indeed living with cancer as a chronic disease, new
problems are emerging in this growing population of so-called 'survivors'.
Persistent or chronic pain is one of the commonest complaints, arising from the
tissue damage caused by the original neoplasm, consequences of surgery and other
therapies, and - especially in older people - multimorbidity. This review
explores some of the principle causes and mechanisms of this phenomenon and
reviews the evidence for their management. RECENT FINDINGS: We review recent
findings regarding persistent pain in adults after surgery, chemotherapy
(including targeted biological therapies), hormone manipulation and radiation
therapy; and osteonecrosis from corticosteroid treatment in children with cancer.
Recent research has revealed some of the molecular, genetic, phenotypic and
psychological factors that predispose some people to developing more persistent
pain after cancer, and their long-term outcomes. SUMMARY: Although persistent
pain in cancer patients surviving after primary treatment has been recognized for
decades, only recently has research shown how this arises and some possible ways
to intervene by prevention and interventions. New holistic models for management
of persistent cancer-related pain are needed.
PMID- 28700362
TI - Bilateral Patellar Tendons Tears After a Fall From Standing Position.
PMID- 28700363
TI - Prospects for elimination of soil-transmitted helminths.
AB - PURPOSE OF REVIEW: Soil-transmitted helminths (STH) are endemic in 120 countries
and are associated with substantial morbidity and loss of economic productivity.
Although current WHO guidelines focus on morbidity control through mass drug
administration (MDA), there is global interest in whether a strategy targeting
disease elimination might be feasible in some settings. This review summarizes
the prospects for switching from control to an elimination strategy. RECENT
FINDINGS: STH control efforts have reduced the intensity of infections in
targeted populations with associated reductions in morbidity. However, adults are
not frequently targeted and remain important reservoirs for reinfection of
treated children. Recent modeling suggests that transmission interruption may be
possible through expanded community-wide delivery of MDA, the feasibility of
which has been demonstrated by other programs. However, these models suggest that
high levels of coverage and compliance must be achieved. Potential challenges
include the risk of prematurely dismantling STH programs and the potential
increased risk of antihelminthic resistance. SUMMARY: Elimination of STH may
offer an opportunity to eliminate substantial STH-related morbidity while
reducing resource needs of neglected tropical disease programs. Evidence from
large community trials is needed to determine the feasibility of interrupting the
transmission of STH in some geographic settings.
PMID- 28700364
TI - Helicobacter pylori infection among patients with liver cirrhosis.
AB - BACKGROUND AND AIM: Inflammatory changes in the stomach caused by Helicobacter
pylori indirectly and directly affect liver function. Moreover, the bacteria may
worsen the course of the liver cirrhosis. The study aimed at evaluating the
incidence of H. pylori infection among patients with liver cirrhosis, depending
on the etiology and injury stage, scored according to Child-Pugh classification.
Stage of esophageal varices and endoscopic inflammatory lesions in the stomach
were evaluated, depending on the presence of H. pylori infection. PATIENTS AND
METHODS: The study included 147 patients with liver cirrhosis: 42 were infected
with hepatitis C virus, 31 were infected with hepatitis B virus, 56 had alcoholic
liver cirrhosis, and 18 had primary biliary cirrhosis. Diagnosis of H. pylori
infection was performed based on the presence of immunoglobulin G antibodies in
serum. RESULTS: H. pylori infection was found in 46.9% of patients. The incidence
of H. pylori infection among patients with postinflammatory liver cirrhosis was
significantly higher (P=0.001), as compared with patients with alcoholic liver
cirrhosis. Ammonia concentration was significantly higher in patients infected
with H. pylori, compared with noninfected individuals (129 vs. 112 MUmol/l;
P=0.002). Incidence of H. pylori infection in patients without esophageal varices
was significantly lower compared with patients with esophageal varices (14 vs.
60%; P<0.001). CONCLUSION: H. pylori infection is significantly more frequent
among patients with postinflammatory liver cirrhosis (infected with hepatitis C
virus or hepatitis B virus) than in patients with alcoholic liver cirrhosis or
primary biliary cirrhosis. H. pylori infection correlates with elevated
concentration of blood ammonia and the incidence of esophageal varices.
PMID- 28700365
TI - Are You Ready for Payment Reform?
PMID- 28700366
TI - Sex Differences in Cannabis Use Disorder Diagnosis Involved Hospitalizations in
the United States.
AB - OBJECTIVES: The study examined sex differences in trend and clinical
characteristics of cannabis use disorder (CUD) diagnosis involved
hospitalizations among adult patients. METHODS: We analyzed hospitalization data
from the 2007-2011 Nationwide Inpatient Samples for patients aged 18-64 years (N
= 15,114,930). Descriptive statistics were used to characterize demographic
variables and to compare the proportions of CUD diagnosis and comorbid patterns
between male and female hospitalizations. Logistic regressions were performed to
examine the association of sex and other demographic variables with CUD
diagnosis. RESULTS: During the study period, 3.3% of male and 1.5% of female
hospitalizations had any-listed CUD diagnoses, and both sexes presented an upward
trend in the number, rate, and proportion of CUD diagnosis. Among
hospitalizations for patients aged 18-25 years, about 1 in 10 males and 1 in 20
females included a CUD diagnosis, and this proportion decreased with age strata.
Mental disorders accounted for the highest proportion of CUD involved inpatient
hospitalizations, and female CUD involved hospitalizations included a higher
proportion of mental disorders that required hospitalized care compared with male
hospitalizations (41% vs 36%). In each sex group, younger age, black race, lower
household income, large metropolitan residence, non-private insurance, substance
use diagnosis, and mental disorders were associated with elevated odds of having
CUD diagnosis. CONCLUSION: The large sample of clinical hospitalization data
suggest an increased trend in CUD diagnosis and sex differences in several
comorbidities with CUD-involved hospital admissions. Prevention and treatment for
CUD should consider sex differences in clinical comorbidities.
PMID- 28700367
TI - Open Adoption Placement by Birth Mothers in Their Twenties.
AB - PURPOSE: The purpose of this study was to summarize birth mothers' descriptions
of unplanned pregnancy experienced in their twenties and how open adoption
influenced their lives. STUDY DESIGN AND METHODS: Naturalistic inquiry was used
with purposive sampling from one agency and telephone interviews of women who
experienced unplanned pregnancy in their twenties and relinquishment through open
adoption. Recorded, transcribed, and deidentified interviews were analyzed for
qualitative themes. RESULTS: Fifteen participants judiciously weighed the open
adoption decision. Over half parented other children prior to placement. Most
knew they could not have parented this child due to life stressors. Placement was
a hard decision, but ongoing contact with birth child and adoptive family was
valued. Open adoption processes made them stronger by being happy that their
child experienced family life with greater opportunities than birth mothers could
offer at the time. Summarized themes used the acronym COMMITTED: C-care deeply
about what is best for the child, O-ongoing open adoption: good and hard, M
meeting together regularly, M-moving on in personal growth, accomplishments, and
milestones, I-independence from previous stressors or crises, T-transitions, T
therapeutic support, E-emotions, D-depression giving way to deepened strength and
personal direction. CLINICAL IMPLICATIONS: Open adoption is reinforced as a
positive resolution of unintended pregnancy for birth mothers in their twenties.
PMID- 28700368
TI - Regional anesthesia and analgesia in cancer care: is it time to break the bad
news?
AB - PURPOSE OF REVIEW: There is ongoing controversy regarding the tumor-protective
effects of regional anesthesia in patients undergoing cancer surgery. Evidence of
up-to-date systematic reviews will be presented alongside recent updates on the
effects of opioids and local anesthetics. RECENT FINDINGS: In recent years, the
literature regarding the effects of regional anesthesia techniques on cancer
recurrence has raised many unanswered questions. Ongoing randomized controlled
trials may not be able to shed light on the controversial discussion regarding
the tumor protective effects of regional anesthesia because the expected effect
size and event rate in those studies may be overstated.Recent more refined animal
data, provides no evidence to suggest that opioids promote cancer recurrence or
facilitate the development of metastatic disease.In addition, local anesthetics
have promising preclinical anticarcinogenic effects that extend beyond their
voltage-gated sodium channel blocking properties and could be of therapeutic
value. SUMMARY: Cancer recurrence in patients undergoing surgery remains a global
burden. Current evidence suggests that regional techniques, opioid analgesia and
local anesthetics in onco-anesthesia may require a tailored individual approach
due to the phenotypic and genotypic heterogeneity within and between different
tumors. The authors surmise that future or ongoing randomized controlled trials
regarding regional anesthesia techniques and cancer outcome may not be able to
reproduce clear results, as it will be challenging to prove the efficacy of one
single intervention (e.g. regional anesthesia) in an otherwise complex
multifactorial perioperative oncological setting.
PMID- 28700369
TI - Pulsed radiofrequency in chronic pain.
AB - PURPOSE OF REVIEW: The increasing number of publications on pulsed radiofrequency
(PRF) treatment of chronic pain reflects the interest for this technique. We
summarize the literature for PRF in five indications: radicular pain, trigeminal
neuralgia (TN), occipital neuralgia, shoulder and knee pain. RECENT FINDINGS: The
efficacy and safety of PRF adjacent to the dorsal root ganglion was documented on
cervical and on lumbar level.PRF has been used for the treatment of TN. The
observed duration of effect is shorter than that of conventional radiofrequency,
but no neurological complications are reported with PRF.PRF of the nervi
occipitales is superior to steroid injections in occipital neuralgia.Several
studies showed that PRF of the nervus suprascapularis may relief shoulder pain
and can improve mobility of the shoulder joint.For the treatment of knee pain,
different nerves have been targeted for PRF treatment. SUMMARY: PRF treatment has
progressively gained a place in the management of chronic pain syndromes. The
concept is appealing because long-lasting effects are reported without
complications. Future research is needed with high quality randomized controlled
trials and identification of the optimal parameters of PRF in clinical practice.
PMID- 28700370
TI - Neuromuscular problems in the ICU.
AB - PURPOSE OF REVIEW: Patients with acute life-threatening neuromuscular disease
require close cooperation between neuromuscular and intensive care specialists to
achieve the best possible outcomes. The problems encountered by these patients
are different from those in traditional neuromuscular practice, and neurologists
consulting in the ICU need a specific skill set to provide useful guidance.
However, outcomes can be very good if treatment is instituted effectively. This
review aims to provide an overview of the most important neuromuscular conditions
encountered in the ICU and enable a practical approach to patient management.
RECENT FINDINGS: New research has provided improved knowledge of the impact of
acute neuromuscular failure on the mechanics of respiration, on the categories of
neuromuscular disease in the ICU, and on the main factors influencing outcomes.
Pitfalls and risks in ICU treatment are better understood. SUMMARY: Evidence
based algorithms for monitoring and treatment have been developed. These advances
enhance the role of the neuromuscular specialist in acute care. The principles of
best practice are discussed in this review.
PMID- 28700372
TI - Immunohistochemical Demonstration of Parvovirus B19 Viral Protein 2 in
Periflexural Exanthema in an Adult, Supporting Antibody-Dependent Enhancement as
Means of Endothelial Uptake of the Virus.
AB - Human parvovirus B19 (B19V) causes a number of skin exanthemas and has been
related to both cutaneous and systemic diseases. Tropism of the virus for the
rapidly proliferating erythroid progenitor cells in the bone marrow and fetal
liver explains the pathogenesis of anemia and fetal hydrops. The cutaneous
lesions of erythema infectiosum and other B19V-related exanthemas have been
attributed to the deposition of immune complexes in the skin. We report on the
immunohistochemical detection of B19V protein in the cytoplasm of dermal
endothelial cells in a case of periflexural exanthema in a 28-year-old woman. An
antibody-dependent enhancement mechanism of entry has been suggested for B19V in
myocardial endothelial cells and could also be involved in B19V-related
exanthemas.
PMID- 28700373
TI - Retiform Purpura After Transcatheter Arterial Chemoembolization: A Case Report.
AB - Cutaneous complications secondary to transcatheter arterial chemoembolization
(TACE) are exceptionally rare and may occur because of nontarget embolization of
terminal vessels supplying the skin. We present a patient who developed painful
retiform purpura on the right flank shortly after TACE for treatment of
hepatocellular carcinoma. Biopsy revealed intravascular tan to yellow amorphous
spherical structures within the dermis, confirming the presence of foreign
material within these vessels. The authors review the literature and discuss
previous cases of skin lesions manifesting after TACE, as well as potential
factors influencing the probability of cutaneous complications. Histopathologic
findings described in similar cases are presented. Prophylactic measures and
attempted treatments to reduce likelihood of long-term injury are also reviewed.
An awareness that cutaneous injury is a rare, but potential complication of
transcatheter arterial embolization, as well as an understanding of management
options is important for any provider using this procedure.
PMID- 28700371
TI - Total pancreatectomy for recurrent acute and chronic pancreatitis: a critical
review of patient selection criteria.
AB - PURPOSE OF REVIEW: Critical review of the indications for total pancreatectomy
and highlight limitations in current diagnostic criteria for chronic
pancreatitis. RECENT FINDINGS: The diagnosis of noncalcific chronic pancreatitis
remains controversial because of an overreliance on nonspecific imaging and
laboratories findings. Endoscopic ultrasound, s-magnetic resonance
cholangiopancreatography, and/or endoscopic pancreatic function testing are often
used to diagnose noncalcific chronic pancreatitis despite the fact that there is
no gold standard for this condition. Abdominal pain is not specific for chronic
pancreatitis and is more likely to be encountered in patients with functional
gastrointestinal disorders based on the high incidence of these conditions. The
duration of pain and opioid analgesic use results in central sensitization that
adversely affects pain outcomes after total pancreatectomy. An alcoholic cause is
associated with poorer pain outcomes after total pancreatectomy. SUMMARY: The
lack of a gold standard for noncalcific chronic pancreatitis limits the
diagnostic accuracy of imaging and laboratory tests. The pain of chronic
pancreatitis is nonspecific and is affected by duration, preoperative opioid use,
and cause. These factors will need to be considered in the development of future
selection criteria for this morbid surgery.
PMID- 28700374
TI - Exenatide-Induced Panniculitis: Utility of the Acid-Fast Stain to Identify
Injected Microspheres.
PMID- 28700375
TI - Comparative Study of Shrinkage in Human Skin, Artificial Human Skin, and Mouse
Skin.
AB - INTRODUCTION: The shrinkage of surgical specimens (SS) is known in human skin
(HS) but has not been studied in an artificial skin (AS) or mouse skin (MS).
OBJECTIVES: To quantify the degree of shrinkage of SS and establish its timing in
HS and an in vitro and animal model to explore the possible causes of this
phenomenon. METHODOLOGY: We collected 100 SS of HS, 50 SS of AS synthesized with
fibrin-agarose biomaterials and 21 SS of MS. The width and length of specimens
were measured before the surgical excision (pre-SE), at 5 minutes postsurgery (ex
vivo), and after 24 hours of fixation in formalin (postfixation). Histological
staining was performed to analyze the differences between HS, AS, and MS that may
explain the differences in shrinkage. RESULTS: Between pre-SE and postfixation,
the width and length shrank by 16.1% and 17.1% in HS, 14.5% and 8.5% in AS, and
26.5% and 23.1% in MS (P < 0.01), respectively. Shrinkage largely occurred
between pre-SE and ex vivo. Cells and interstitial fibers were scant in AS and
abundant in MS. CONCLUSIONS: Almost all of the shrinkage occurred during the
first 5 minutes postsurgery. According to the AS model findings, 53.6% of SS
shrinkage would be explained by the action of dermal fibers and other cellular
components of the dermis.
PMID- 28700376
TI - Eruptive Multifocal Cutaneous Mucinous Cysts.
AB - Cutaneous cysts lined by mucinous epithelium are rare entities. We report an
unusual case of a 60-year-old female patient who presented with a 2-month history
of eruptive cystic papules on her right thigh. Histopathologic study showed
multiple, multiloculated cysts located in the dermis lined by nonciliated
mucinous epithelium. The cyst lining was positive for AE1/AE3, CK7, CK20, and
GCDFP15. Patchy positivity was noted on the p53 stain. Attenuated Sox10 positive
cells were identified, raising the possibility of sweat duct origin; however, no
myoepithelial layer was identified by p63 staining. Mullerian markers, including
ER, PR, WT1, and Pax8, were negative. We propose this as a unique case that may
represent mucinous metaplasia of a cystic sweat duct lesion. Here, we review the
literature of mucinous and other glandular cutaneous cysts.
PMID- 28700377
TI - In Response.
PMID- 28700378
TI - Editorial introduction.
PMID- 28700379
TI - Optimizing dietary patterns to decrease premature mortality.
PMID- 28700380
TI - Autophagy and hepatic steatosis.
PMID- 28700381
TI - Cholesterol: a dark horse in signalling race.
PMID- 28700382
TI - Mandatory Reporting of Intimate Partner Violence: An Ethical Dilemma for Forensic
Nurses.
AB - Nearly all states and provinces have laws mandating licensed healthcare
professionals to report to law enforcement suspicions and allegations of the
abuse of children, older adults, and disabled persons and all incidents of
violence by a deadly weapon. However, a few states in the United States
additionally mandate providers to report all injuries resultant from reported or
suspected domestic/intimate partner violence. This can present a challenge to
forensic nurses seeking to protect patient confidentiality and autonomy. This
challenge becomes further compounded when a patient desiring to remain anonymous
reports sexual assault by their partner, accompanied by bodily injury. This case
report explores one such scenario that occurred in a rural Colorado Emergency
Department, the issues this presents to forensic nurses, and possible responses.
PMID- 28700383
TI - The Use of the Clinical Dementia Rating Scale Sum of Boxes Scores in Detecting
and Staging Cognitive Impairment/Dementia in Brazilian Patients With Low
Educational Attainment.
AB - The aim of this study was to evaluate the Clinical Dementia Rating Scale sum of
the boxes (CDR-SB) diagnostic validity in detecting and staging cognitive
impairment/dementia in a sample of Brazilian patients with amnestic mild
cognitive impairment (aMCI), Alzheimer disease (AD), and vascular dementia (VD),
of low educational attainment. Data were obtained from the Dementia Clinic of
Hospital de Clinicas de Porto Alegre database and included 407 participants (115
healthy elderly, 41 aMCI, 165 AD, and 86 VD). Receiver operating characteristic
curves were generated to detect best CDR-SB cutoffs. Average education was 4
years. A CDR-SB cutoff >=0.5 was obtained to correctly identify MCI from normal
controls (sensitivity of 100% and specificity of 98.3%). The cutoff >=4.5
correctly identified aMCI from dementia altogether or separately (AD and VD)
(sensitivity of 96.4% and specificity of 100%) in 96.9% of the individuals.
Similar AUC was found for <=4 and >4 years of education. The CDR-SB showed good
clinical validity to detect and classify severity of cognitive impairment
Brazilian patients with low educational attainment. Findings were similar to the
original study carried out with higher educated individuals.
PMID- 28700385
TI - In Reply.
PMID- 28700384
TI - Update on Graves disease: advances in treatment of mild, moderate and severe
thyroid eye disease.
AB - PURPOSE OF REVIEW: To report the most recent therapeutic advances of thyroid eye
disease (TED) and offer general recommendations for management of TED. RECENT
FINDINGS: Treatment of Graves ophthalmopathy is traditionally based on the use of
high doses of corticosteroids and/or radiotherapy (RT) to decrease the activity
of the disease, with the subsequent proptosis, strabismus and eyelid deformites
treated with different surgical procedures. In recent years, the evidence that
oxidative stress plays a relevant role in exacerbating TED severity has
encouraged the use of antioxydative agents such as selenium, which has shown a
capacity in limiting the disease progression. In addition, reports have shown the
effectiveness of biological immunosuppressive agents in the management of TED.
The main advantage of these medications seems to be the long lasting effects,
which may reduce recurrence, and effectiveness in steroid-resistant cases. The
reported increased accuracy of imaging techniques in evaluating fat and muscle
volumes may provide useful information for surgical management. SUMMARY: The use
of selenium, in mild TED, seems to limit disease progression without carrying the
risk of relevant side-effects. Biological agents may provide an effective and
long lasting block of the inflammatory activity of TED, with a possible lower
risk of recurrence and reduction in the need for surgical intervention in
moderate-to-severe disease. The accurate evaluation of fat and muscle volume,
using a recently published algorithm for imaging, gives relevant information for
preoperative assessment, allowing the customization of orbital decompression.
PMID- 28700387
TI - Treatment of Recurrent Lumbar Disc Herniation With or Without Fusion in Workers'
Compensation Subjects.
AB - STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To determine outcomes after
reoperation discectomy with or without fusion surgery for recurrent lumbar disc
herniation (RLDH) in the workers' compensation (WC) population. SUMMARY OF
BACKGROUND DATA: RLDH is estimated to occur in 7% to 24% of patients after
discectomy. There are two main surgical options after reherniation: a revision
discectomy (RD), or an RD combined with fusion (RDF). METHODS: A total of 10,592
patients received lost-work compensation from the Ohio Bureau of Workers'
Compensation for a lumbar disc herniation between 2005 and 2012. Patients with
lumbar spine comorbidities, a smoking history, or multilevel surgery were
excluded. One hundred two patients had RD alone for RLDH and 196 had RDF
procedures. The primary outcome was whether subjects returned to work (RTW).
RESULTS: A total of 298 WC patients met our study criteria, including 230 (77.2%)
men and 68 (22.8%) women with an average age of 39.4 years (range 19-66). The RDF
group had lower rates of RTW than the RD group (27.0% vs 40.2%; P = 0.03).
Multivariate regression analysis showed that reoperation with discectomy and
fusion (P = 0.04; odds ratio [OR] = 0.56), psychiatric illness (P < 0.01; OR =
0.19), and opioid analgesic use within 1 month of reoperation (P < 0.01; OR =
0.44) were independent negative predictors of RTW. RDF patients were supplied
with opioids for 252.3 days longer (P < 0.01) and incurred $34,914 (31.8%) higher
medical costs (P < 0.01) than the RD alone group. CONCLUSION: We analyzed
outcomes after operative management of RLDH in the WC population. WC patients
receiving RDF had lower RTW rates, higher costs, and a longer duration of
postoperative opioid use than those receiving RD alone. This information allows
for informed patient management decisions and suggests that fusion should be
reserved for patients with clear indications for its use. We are unable to
conclude what treatment method is best, but rather we provide a baseline for
future studies. LEVEL OF EVIDENCE: 3.
PMID- 28700389
TI - Intraoperative Optical Coherence Tomography-Guided Retrolenticular Vitreous
Peeling in Diabetic Vitreous Hemorrhage.
PMID- 28700390
TI - BARTONELLA HENSELAE NEURORETINITIS ASSOCIATED WITH CENTRAL RETINAL VEIN
OCCLUSION, CHOROIDAL ISCHEMIA, AND ISCHEMIC OPTIC NEUROPATHY.
AB - PURPOSE: We describe a healthy 37-year-old man with Bartonella henselae (B.
henselae) neuroretinitis with concurrent central retinal vein occlusion and
ischemic optic neuropathy resulting in optic atrophy and choroidal ischemia.
METHODS: Case report. RESULTS: A 37-year-old man presented with unilateral
decreased vision and a fundus examination consistent with neuroretinitis. Further
imaging review supported a concurrent diagnosis of central retinal vein
occlusion. Although initially negative, repeat serological testing for B.
henselae infection was positive. Multimodal imaging displayed severe outer
retinal disruption, ischemic optic neuropathy, and choroidal ischemia. The
patient demonstrated near complete resolution of fundus findings and restoration
of outer retinal architecture. Residual findings included optic disk pallor and
ischemic choroidopathy. DISCUSSION: B. henselae neuroretinitis may be associated
with concurrent retinal vascular occlusive disease and ischemic optic neuropathy.
Central retinal vein occlusion and choroidal ischemia leading to optic nerve
atrophy are additional sequelae further expanding the clinical spectrum of this
entity.
PMID- 28700391
TI - Human T-lymphotropic virus type 1 infection and disease in Spain.
AB - : Human T-lymphotropic virus type 1 (HTLV-1) infection is a neglected disease
despite roughly 15 million people are chronically infected worldwide. Lifelong
less than 10% of carriers develop life-threatening diseases, mostly a subacute
myelopathy known as tropical spastic paraparesis (TSP) and a lymphoproliferative
disorder named adult T-cell leukemia (ATL). HTLV-1 is efficiently transmitted
perinatally (breastfeeding), sexually (more from men to women) and parenterally
(transfusions, injection drug user (IDU), and transplants). To date there is
neither prophylactic vaccine nor effective antiviral therapy. A total of 327
cases of HTLV-1 infection had been reported at the HTLV-1 Spanish registry until
December 2016, of whom 34 had been diagnosed with TSP and 25 with ATL. Overall
62% were Latin American immigrants and 13% were persons of African origin. The
incidence of HTLV-1 in Spain has remained stable for nearly a decade with 20-25
new cases yearly. Of the 21 newly diagnosed HTLV-1 cases during year 2016, one
was a native Spaniard pregnant woman, and four presented with symptomatic
disease, including three with ATL and one with TSP. Underdiagnosis of HTLV-1 in
Spain must be high (iceberg model), which may account for the disproportionate
high rate of symptomatic cases (almost 20%) and the late recognition of
preventable HTLV-1 transmissions in special populations, such as newborns and
transplant recipients. Our current estimate is of 10 000 persons living with HTLV
1 infection in Spain. Given the large flux of immigrants and visitors from HTLV-1
endemic regions to Spain, the expansion of HTLV-1 screening policies is
warranted. At this time, it seems worth recommending HTLV testing to all
donor/recipient organ transplants and pregnant women regardless place of birth.
Although current leukoreduction procedures largely prevent HTLV-1 transmission by
blood transfusions, HTLV testing of all first-time donors should be cost
effective contributing to unveil asymptomatic unaware HTLV-1 carriers.
PMID- 28700392
TI - CD4+/CD8+ ratio restoration in long-term treated HIV-1-infected individuals.
AB - OBJECTIVES: A persistently low CD4/CD8 ratio despite virological control reflects
a higher risk of morbidity in HIV-infected individuals. The objective of the
study was to assess the probability and determinants of ratio restoration (>=1)
during long-term combined antiretroviral therapy (cART). DESIGN: Study cohort
based on the French Hospital Database on HIV (ANRS CO4). METHODS: Antiretroviral
naive HIV-1-infected individuals were included if they achieved virological
control (plasma HIV RNA <= 500 copies/ml) within 9 months following cART, started
between 2000 and 2010. Cumulative incidence of ratio restoration after
virological control and predictive factors of such a favorable outcome were
studied taking into account 'virological failure', 'loss to follow-up', and
'death' as competing risks for ratio restoration. RESULTS: Among the 10012
individuals included, the probability of CD4/CD8 ratio restoration was 30% (95%
confidence interval, 29-31) at 8 years, ranging from 17% (15 to 19) among
individuals with AIDS, to 45% (41 to 50) in people with CD4 at least 500
cells/MUl at cART introduction. The main factors associated with ratio
restoration were cART started during primary HIV infection whatever the CD4 cell
count, or starting at CD4 at least 500 cells/MUl while not in primary HIV
infection [subdistribution hazard ratio = 1.67 (95% confidence interval, 1.13
2.47) and 2.26 (1.92-2.66) respectively, compared with starting cART at 200-349
CD4 cells/MUl], and starting cART in recent years [subdistribution hazard ratio =
2.38 (2.01-2.83) in 2009-2010, compared with 2000-2002]. Higher baseline CD8 cell
count was negatively associated with ratio restoration. CONCLUSION: At 8 years,
only one-third of individuals achieved CD4/CD8 ratio restoration with sustained
virological control. Treatment at the earliest stage, and starting cART in recent
years appeared to be key determinants.
PMID- 28700393
TI - Ten-year trends in antiretroviral therapy persistence among US Medicaid
beneficiaries.
AB - OBJECTIVE: Whether the rate of HIV antiretroviral therapy (ART) persistence has
improved over time in the United States is unknown. We examined ART persistence
trends between 2001 and 2010, using non-HIV medications as a comparator. METHODS:
We conducted a retrospective cohort study using Medicaid claims. We defined
persistence as the duration of treatment from the first to the last fill date
before a 90-day permissible gap and used Kaplan-Meier curves and Cox proportional
hazard models to assess crude and adjusted nonpersistence. The secular trends of
ART persistence in 43 598 HIV patients were compared with the secular trends of
persistence with angiotensin-converting enzyme inhibitors or angiotensin II
receptor blockers (ACEI/ARB), statins, and metformin in non-HIV-infected patients
and subgroups of HIV patients who started these control medications while using
ART. RESULTS: Median time to ART nonpersistence increased from 23.9 months in
2001-2003 to 35.4 months in 2004-2006 and was not reached for those starting ART
in 2007-2010. In adjusted models, ART initiators in 2007-2010 had 11% decreased
hazard of nonpersistence compared with those who initiated in 2001-2003 (P <
0.001). For non-HIV patients initiating angiotensin-converting enzyme
inhibitors/angiotensin II receptor blockers (ACEI/ARB), statins, and metformin,
the hazard ratios for nonpersistence comparing 2007-2010 to 2001-2003 were 1.07,
0.94, and 1.02, respectively (all P < 0.001). For HIV patients initiating the
three control medications, the hazard ratios of nonpersistence comparing 2007
2010 to 2001-2003 were 0.71, 0.65, and 0.63, respectively (all P < 0.001).
CONCLUSION: Persistence with ART improved between 2001 and 2010. Persistence with
control medications improved at a higher rate among HIV patients using ART than
HIV-negative controls.
PMID- 28700394
TI - Medication adherence, condom use and sexually transmitted infections in
Australian preexposure prophylaxis users.
AB - OBJECTIVE: HIV preexposure prophylaxis (PrEP) decreases risk of HIV acquisition;
however, its efficacy is closely dependent on adherence. There is also concern
that the preventive effect of PrEP may be offset by risk compensation, notably an
increase in condomless anal sex. DESIGN: Multisite, open-label demonstration
study that recruited people at current or recent risk of HIV infection in
Melbourne, Australia. METHODS: Participants were recruited from three general
practice clinics and one sexual health clinic in Melbourne and consented to take
daily tenofovir/emtricitabine (TFV/FTC) for 30 months. Sexual practice data, HIV
and sexually transmitted infection (STI) test results were collected at baseline
and 3-monthly during follow-up. PrEP adherence was evaluated by self-report at
clinical visits, online surveys, refill-based assessments and dried blood spot
testing. We present a 12-month interim analysis. RESULTS: A total of 114 people
were recruited. We observed a significant decline in condom use which occurred
concomitantly with a significant increase in STIs over the first 12 months of
PrEP. Incidence (per 100 person-years) of any STI was 43.2 and 119.8 at months 0
3 and 3-12, respectively [incidence rate ratio 2.77 (1.52, 5.56)]. Adherence to
PrEP medication was high by all measures, including 6 month TFV/FTC levels in
dried blood spot. CONCLUSION: We found a significant reduction in condom use and
an increase in STIs over the first 12 months of follow-up. High medication
adherence rates occurring with a decline in condom use and a rise in STIs,
suggest that prevention, early detection and treatment of STIs is a chief
research priority in the current era of HIV PrEP.
PMID- 28700395
TI - Neuropsychiatric events and dolutegravir in HIV patients: a worldwide issue
involving a class effect.
PMID- 28700396
TI - HIV-induced uveitis: would you recognize it if it looked straight at you?
PMID- 28700397
TI - Successful implementation of hepatitis C virus treatment in two large HIV clinics
in Amsterdam: hepatitis C virus treatment cascade of care.
PMID- 28700398
TI - The Role of Preoperative Steroids in Atraumatic Cochlear Implantation Surgery.
AB - HYPOTHESIS: Depth of insertion is related to the extent of tissue response and
low frequency hearing loss. Intravenous steroids have greatest effect in reducing
postimplantation fibrosis and hearing loss in the presence of significant
electrode insertion trauma, when compared with saline treatment. BACKGROUND:
Experiments exploring the enhancement of cochlear implantation (CI) outcomes with
glucocorticosteroids have produced mixed results, possibly due to lack of
standardization of the CI model. METHODS: Forty-eight normal-hearing guinea pigs
were randomly implanted with a highly flexible electrode to a depth of 1.5, 3.0,
or 5.0 mm. For each insertion depth, sub-cohorts received either intravenous
saline ("saline") or dexamethasone ("steroid") 60 minutes before implantation.
Shifts in electrocochleography thresholds at 2 to 32 kHz were determined before
and 4 weeks after implantation. Cochleae were harvested and imaged. RESULTS: Low
frequency hearing loss was greatest with 5.0 mm insertions. Fracture of the
osseous spiral lamina and/or fibrotic involvement of the round window membrane
exacerbated hearing loss. The extent of intracochlear fibrosis was directly
related to the depth of insertion. Steroids reduced the intracochlear tissue
response for deepest insertions and in apical regions of the cochlea where
basilar membrane contact was prevalent. Steroids preserved no more hearing than
saline at all insertion depths. CONCLUSION: Cochlear trauma influenced
postimplantation hearing loss and steroid effect on fibrosis. Fibrosis, and to a
lesser extent, postimplantation hearing loss increased proportionally to the
depth of insertion. Steroids did not influence fibrosis relating to the
cochleostomy, but could reduce scarring as the electrode negotiated the hook
region or near the electrode tip.
PMID- 28700399
TI - Ellipsoid Smooth Muscle Tumor of the Lower Eyelid: An Exploration of Its Possible
Origin.
AB - Ocular adnexal smooth muscle masses/neoplasms are extremely rare. Such lesions
are comparatively more common in the conjunctiva than in the orbit and are most
unusual in the eyelid. A 58-year-old woman slowly developed over 4 months a firm,
movable sausage-shaped lesion in the deep lateral half of the right lower eyelid.
The lesion ran parallel to and above the orbital rim. At surgery, the lesion was
located between the orbicularis muscle and the inferior orbital septum. The term
ellipsoid is used descriptively and does not imply any particular biologic
behavior. Immunohistochemical evaluation revealed smooth muscle actin and desmin
positivity. Due to the ubiquity of small blood vessels and the absence of smooth
muscle bundles in the potential space between the orbicularis striated muscle and
the inferior orbital septum, venular smooth muscle emerges as a highly likely
source for the lesion.
PMID- 28700400
TI - Treatment of Pediatric IgG4-Related Orbital Disease With TNF-alpha Inhibitor.
AB - The authors describe a 9-year-old female who presented with swelling, proptosis,
and tenderness of the right upper eyelid and MRI imaging demonstrating right
lacrimal gland enlargement. After failing treatment with corticosteroids, the
patient underwent a biopsy that was consistent with IgG4-related orbital disease.
She was subsequently successfully treated with adalimumab (TNF-alpha inhibitor).
This is the first case report of the successful use of a TNF-alpha inhibitor for
the treatment of IgG4-related orbital disease in a child.
PMID- 28700401
TI - Wiesner Nevus of the Eyelid.
AB - A healthy 31-year-old female presented with an elevated vascular lesion on the
right lower eyelid margin. Histology results from excisional biopsy demonstrated
a range of intradermally nested atypical melanocytes with negative staining for
BRCA1-associated protein 1, confirming the diagnosis of Wiesner nevus. Wiesner
nevi may be a cutaneous hallmark of the BRCA1-associated protein 1-associated
cancer susceptibility syndrome, and to our knowledge, this is the first report of
such a lesion presenting anywhere on the ocular adnexa.
PMID- 28700402
TI - Fibromyxoma of the Tarsus: A Case Report.
AB - A 61-year-old woman presented with a slow-growing mass on the right upper eyelid.
The hard, fixed, and nontender mass was apparent on the right upper eyelid. It
was immobile, and it seemed to be adhered to the tarsus. Total excision of the
mass was performed. A histopathological examination revealed a solid mass with
fibrous and myxoid areas with scattered spindle- to stellate-shaped cells in a
fibromyxoid matrix. The immunochemistry examination stained positively for CD34
and CD99. Based on these findings, the lesion was diagnosed as a tarsal
fibromyxoma. Although rare, a fibromyxoma originating from the tarsus should be
considered in the differential diagnosis of solid tarsal lesions.
PMID- 28700403
TI - A Lacrimal Gland Choristoma of the Lacrimal Sac.
AB - Choristomatous lacrimal gland tissue has been detected in many different sites of
the ocular adnexa, but has never before been convincingly described in the
submucosa of the lacrimal sac. A 77-year-old woman with epiphora had a biopsy of
the sac wall preformed during a dacryocystorhinostomy that contained such a
lacrimal choristoma. Zymogen granules were found in the cytoplasm of the
secretory cells with the periodic acid-Schiff reaction. No mucus-producing cells,
as found in normal sac submucosal glands, were detected using the Alcian blue,
mucicarmine, and Gomori methenamine silver histochemical stains. Gross cystic
fluid protein-15 positivity was demonstrated immunohistochemically. The clinical
implications of this choristoma are explored.
PMID- 28700404
TI - Short course of oral lithium therapy as an adjunct in patients with
thyrotoxicosis who failed initial radioiodine therapy: should this be worthwhile
to consider in the absence of contraindications?
PMID- 28700405
TI - Characterization of viability, scarring and hibernation of the myocardium
supplied by epicardial coronary arteries with low flow grades.
AB - OBJECTIVE: The aim of this study was to analyse the relationship between reduced
coronary artery flow and myocardial viability, scarring and hibernation. PATIENTS
AND METHODS: Coronary flow grades and collateral vessels were scored using the
thrombolysis in myocardial infarction trial (TIMI) and the Rentrop and Cohen
scoring systems, respectively. N-ammonia and fluorine-18-fluorodeoxyglucose (F
FDG) are the perfusion and metabolic markers on PET, respectively. The left
ventricle was divided into three coronary territories. The area with the highest
N-ammonia uptake was considered the reference region. Myocardial regions with F
FDG uptake of at least 50% of the reference region were considered viable and
those with F-FDG uptake less than 50% of the reference region were considered
scarred. Hibernation was considered present if the viable myocardium had
significant wall motion abnormality. RESULTS: There were 80 (71 males) patients
with 240 myocardial territories. TIMI 2-3 arteries supplied 151 regions (group
A), and 89 regions were supplied by TIMI 0-1 arteries (group B). Viable
myocardium was present in 140 (93%) regions of group A and in 76 (85%) regions of
group B (P=0.068). Scarring was present in 40 (26%) regions in group A and in 49
(55%) regions in group B (P<0.0001). Wall motion data were available in 215
regions: 133 regions in group A and 82 regions in group B. Hibernating myocardium
was predicted in 36 (28%) regions in group A and in 34 (41%) regions in group B
(P<0.05). CONCLUSION: Myocardial regions supplied by arteries with TIMI 0-1 are
characterized by significantly increased incidence of hibernation and scarring.
Video abstract: http://links.lww.com/NMC/A115.
PMID- 28700406
TI - The Use of Multistate Models to Examine Associations of Stress and Adherence With
Transitions Among HIV Care States Observed in a Clinical HIV Cohort.
AB - BACKGROUND: The "cascade of care" is a framework for quantifying the trajectory
of people with HIV along the continuum of HIV care. We extended this framework to
recognize that individuals may transition back and forth between states of care
and to identify factors associated with movement among states of care over time,
with particular focus on stress, depression, and adherence. METHODS: The Ontario
HIV Treatment Network Cohort Study is a multisite HIV clinical cohort. We
analyzed data from participants who had initiated antiretroviral therapy,
achieved virologic suppression, completed >=1 study questionnaire including
psychosocial data, and had >=1 viral load (VL) result within 2 years of a
questionnaire. Follow-up time from the first suppressed VL was divided into 6
month intervals and classified into 1 of 3 states for HIV care retention: (1)
suppressed VL (VL <50 copies/mL), (2) unsuppressed VL (VL >50 copies/mL), and (3)
unobserved. Multistate models were used to determine the association of
transitioning between states and time-updated demographic and clinical
characteristics. RESULTS: In total, 1842 participants were included. After
multivariable adjustment, poor adherence [hazard ratio (HR) 1.88, 95% confidence
interval (CI): 1.19 to 2.98) and stress (HR = 1.38; 95% CI: 1.04 to 1.83) were
associated with transitions from suppressed to unsuppressed VL. Similarly, low
adherence (HR = 1.52; 95% CI: 1.14 to 2.04) and stress (HR = 1.25; 95%: 1.03,
1.51) were associated with transitions from suppressed to unobserved states.
CONCLUSIONS: Higher levels of stress and low adherence are associated with
transitions to less favorable states of care. Interventions to manage stress and
facilitate adherence may improve engagement in HIV care.
PMID- 28700407
TI - Estimated HIV Incidence, Prevalence, and Undiagnosed Infections in US States and
Washington, DC, 2010-2014.
AB - INTRODUCTION: The burden of HIV infection and health outcomes for people living
with HIV varies across the United States. New methods allow for estimating
national and state-level HIV incidence, prevalence, and undiagnosed infections
using surveillance data and CD4 values. METHODS: HIV surveillance data reported
to the Centers for Disease Control and Prevention and the first CD4 value after
diagnosis were used to estimate the distribution of delay from infection to
diagnosis based on a well-characterized CD4 depletion model. This distribution
was used to estimate HIV incidence, prevalence, and undiagnosed infections during
2010-2014. Estimated annual percentage changes (EAPCs) were calculated to assess
trends. RESULTS: During 2010-2014, HIV incidence decreased 10.3% (EAPC = -3.1%)
and the percentage of undiagnosed infection decreased from 17.1% to 15.0% (EAPC =
-3.3%) in the United States; HIV prevalence increased 9.1% (EAPC = 2.2%). Among
36 jurisdictions with sufficient data to produce stable estimates, HIV incidence
decreased in 3 jurisdictions (Georgia, New York, and District of Columbia) and
the percentage of undiagnosed HIV infections decreased in 2 states (Texas and
Georgia). HIV prevalence increased in 4 states (California, Florida, Georgia, and
Texas). In 2014, southern states accounted for 50% of both new HIV infections and
undiagnosed infections. CONCLUSION: HIV incidence and undiagnosed infection
decreased in the United States during 2010-2014; however, outcomes varied by
state and region. Progress in national HIV prevention is encouraging but
intensified efforts for testing and treatment are needed in the South and states
with high percentages of undiagnosed infection.
PMID- 28700408
TI - Three- versus four-factor prothrombin complex concentrates for "factor-based"
resuscitation in a porcine hemorrhagic shock model.
AB - BACKGROUND: Bleeding is a leading cause of preventable death after severe injury.
Prothrombin complex concentrates (PCC) treat inborn coagulation disorders and
reverse oral anticoagulants, but are proposed for use in "factor-based"
resuscitation strategies. Few studies exist for this indication in acidosis, or
that compare 3-factor PCC (3PCC) versus 4-factor PCC (4PCC) products. We aimed to
assess and compare their safety and efficacy in a porcine model of severe
hemorrhagic shock and coagulopathy. METHODS: Twenty-five adult Yorkshire swine
underwent 35% volume hemorrhage, ischemia-reperfusion injury, and protocolized
crystalloid resuscitation. Seventeen animals were randomized at 4 hours after
model creation to receive a 45-IU/kg dose of either 3PCC or 4PCC. An additional
eight animals received autologous plasma transfusion before 4PCC to better
characterize response to PCC. Individual factor levels were drawn at 4 hours and
6 hours. RESULTS: The model created significant acidosis with mean pH of 7.21 and
lactate of 9.6 mmol/L. After PCC, 66.7% of 3PCC animals and 25% of 4PCC animals
(regardless of plasma administration) developed consumptive coagulopathy. The
animals that developed consumptive coagulopathy had manifested the "lethal triad"
with lower temperatures (36.3 degrees C vs. 37.8 degrees C), increased acidosis
(pH, 7.14 vs. 7.27; base excess, -12.1 vs. -6.5 mEq/L), and worse coagulopathy
(prothrombin time, 17.1 vs. 14.6 seconds; fibrinogen, 87.9 vs. 124.1 mg/dL) (all
p < 0.05). In the absence of a consumptive coagulopathy, 3PCC and 4PCC improved
individual clotting factors with transient improvement of prothrombin time, but
there was significant depletion of fibrinogen and platelets with no lasting
improvement of coagulopathy. CONCLUSION: PCC failed to correct coagulopathy and
was associated with fibrinogen and platelet depletion. Of greater concern, PCC
administration resulted in consumptive coagulopathy in the more severely ill
animals. The incidence of consumptive coagulopathy was markedly increased with
3PCC versus 4PCC, and these products should be used with caution in this setting.
PMID- 28700409
TI - Indication and survival bias: Threats to resuscitative endovascular balloon
occlusion of the aorta outcomes research.
PMID- 28700410
TI - Quantifying and exploring the recent national increase in surgical stabilization
of rib fractures.
AB - BACKGROUND: Surgical stabilization of rib fractures (SSRF) has become pivotal in
the management of severe chest injuries. Recent literature supports improved
outcomes and mortality in severe fracture and flail chest patients who undergo
SSRF compared with nonoperative management (NOM). A 2014 National Trauma Data
Bank review provided a point prevalence of 0.7% SSRF in flail patients. We
hypothesize that this prevalence is increasing and that temporal, regional, and
American College of Surgeons (ACS) trauma designation vary in SSRF utilization.
METHODS: Retrospective National Trauma Data Bank data were extracted for years
2007 to 2014 for patients with rib fractures. Cases were divided into SSRF versus
NOM. SSRF frequencies were analyzed across year, region, and ACS level. Patient
demographics, injury severity score, number of fractured ribs, and hospital
characteristics were identified for multivariable analysis. RESULTS: Between 2007
and 2014, 687,137 rib fracture patients were identified; 29,981 (4.36%) underwent
SSRF. SSRF increased by 76% nationally during the review period (odds ratio [OR],
1.59; 95% confidence interval [CI], 1.50-1.67; p < 0.001). Compared with the
north, SSRF was used more in the west (OR, 1.6; 95% CI, 1.57-1.71), south (OR,
1.48; 95% CI, 1.43-1.54), then midwest (OR, 1.4; 95% CI, 1.34-1.46; p < 0.001).
Although likelihood of SSRF is higher at ACS Level I (LI) centers compared with
Level II (LII) centers (OR, 0.67; 95% CI, 0.65-0.69) or Level III (LIII) (OR,
0.24; 95% CI, 0.22-0.26); p < 0.001), frequency of SSRF increased dramatically at
lower-level centers from 2007 to 2014 (LI, 41.4%; LII, 53.6%; LIII,
60.0%).Overall SSRF mortality was 1.58% (NOM, 5.3%; p < 0.001), decreasing
significantly between 2007 and 2014 (p < 0.0001). ACS LII had higher mortality
than LI (OR, 1.82; 95% CI, 1.39-2.39; p < 0.0001), controlled by Injury Severity
Score. CONCLUSION: Utilization of SSRF has risen considerably nationwide.
Prevalence varies by region and ACS level. Although greatest growth is occurring
at LII hospitals, mortality is also the highest at these centers. Further
research is needed to determine the need for regionalization of care and center
of excellence designation. LEVEL OF EVIDENCE: Epidemiological study, level III.
PMID- 28700412
TI - Parathyroid hormone as a marker for hypoperfusion in trauma: A prospective
observational study.
AB - BACKGROUND: Hyperparathyroidism is common in critical illness. Intact parathyroid
hormone has a half-life of 3 minutes to 5 minutes due to rapid clearance by the
liver, kidneys, and bone. In hemorrhagic shock, decreased clearance may occur,
thus making parathyroid hormone a potential early marker for hypoperfusion. We
hypothesized that early hyperparathyroidism predicts mortality and transfusion in
trauma patients. METHODS: A prospective observational study was performed at a
Level I trauma center in consecutive adult patients receiving the highest level
of trauma team activation. Parathyroid hormone and lactic acid were added to the
standard laboratory panel drawn in the trauma bay on arrival, before the
administration of any blood products. The primary outcomes assessed were
transfusion in 24 hours and mortality. RESULTS: Forty-six patients were included.
Median age was 47 years, 82.6% were men, 15.2% suffered penetrating trauma, and
21.7% died. Patients who were transfused in the first 24 hours (n = 17) had
higher parathyroid hormone (182.0 pg/mL vs. 73.5 pg/mL, p < 0.001) and lactic
acid (4.6 pg/mL vs. 2.3 pg/mL, p = 0.001). Patients who did not survive to
discharge (n = 10) also had higher parathyroid hormone (180.3 pg/mL vs. 79.3
pg/mL, p < 0.001) and lactic acid (5.5 mmol/L vs. 2.5 mmol/L, p = 0.001). For
predicting transfusion in the first 24 hours, parathyroid hormone has an area
under the receiver operating characteristic curve of 0.876 compared with 0.793
for lactic acid and 0.734 for systolic blood pressure. Parathyroid hormone has an
area under the receiver operating characteristic curve of 0.875 for predicting
mortality compared with 0.835 for lactic acid and 0.732 for systolic blood
pressure. CONCLUSION: Hyperparathyroidism on hospital arrival in trauma patients
predicts mortality and transfusion in the first 24 hours. Further research should
investigate the value of parathyroid hormone as an endpoint for resuscitation.
LEVEL OF EVIDENCE: Prognostic, level II.
PMID- 28700413
TI - Venous thromboembolism after major venous injuries: Competing priorities.
AB - BACKGROUND: Venous thromboembolism (VTE) after major vascular injury (MVI) is
particularly challenging because the competing risk of thrombosis and
embolization after direct vessel injury must be balanced with risk of bleeding
after surgical repair. We hypothesized that venous injuries, repair type, and
intraoperative anticoagulation would influence VTE formation after MVI. METHODS:
A multi-institution, retrospective cohort study of consecutive MVI patients was
conducted at three urban, Level I centers (2005-2013). Patients with MVI of the
neck, torso, or proximal extremities (to elbows/knees) were included. Our primary
study endpoint was the development of VTE (DVT or pulmonary embolism [PE]).
RESULTS: The 435 major vascular injury patients were primarily young (27 years)
men (89%) with penetrating (84%) injuries. When patients with (n = 108) and
without (n = 327) VTE were compared, we observed no difference in age, mechanism,
extremity injury, tourniquet use, orthopedic and spine injuries, damage control,
local heparinized saline, or vascular surgery consultation (all p > 0.05). VTE
patients had greater Injury Severity Score (ISS) (17 vs. 12), shock indices (1
vs. 0.9), and more torso (58% vs. 35%) and venous (73% vs. 48%) injuries, but
less often received systemic intraoperative anticoagulation (39% vs. 53%) or
postoperative enoxaparin (47% vs. 61%) prophylaxis (all p < 0.05). After
controlling for ISS, hemodynamics, injured vessel, intraoperative
anticoagulation, and postoperative prophylaxis, multivariable analysis revealed
venous injury was independently predictive of VTE (odds ratio, 2.7; p = 0.002).
Multivariable analysis of the venous injuries subset (n = 237) then determined
that only delay in starting VTE chemoprophylaxis (odds ratio, 1.3/day; p = 0.013)
independently predicted VTE after controlling for ISS, hemodynamics, injured
vessel, surgical subspecialty, intraoperative anticoagulation, and postoperative
prophylaxis. Overall, 3.4% of venous injury patients developed PE, but PE rates
were not related to their operative management (p = 0.72). CONCLUSION: Patients
with major venous injuries are at high risk for VTE, regardless of intraoperative
management. Our results support the immediate initiation of postoperative
chemoprophylaxis in patients with major venous injuries. LEVEL OF EVIDENCE:
Therapeutic/care management, level IV.
PMID- 28700414
TI - Evaluation of gut-blood barrier dysfunction in various models of trauma,
hemorrhagic shock, and burn injury.
PMID- 28700415
TI - The role of monogenic disease in children with very early onset inflammatory
bowel disease.
AB - PURPOSE OF REVIEW: Inflammatory bowel disease (IBD) is a multifactorial disease
caused by dysregulated immune responses to commensal or pathogenic intestinal
microbes, resulting in chronic intestinal inflammation. Patients diagnosed with
IBD occurring before the age of 5 are a unique population, known as very early
onset (VEO)-IBD and can be phenotypically and genetically distinct from older
onset IBD. We aim to review the clinical presentation of children with VEO-IBD
and recent discoveries that point to genomic drivers of disease that may impact
our therapeutic decisions. RECENT FINDINGS: VEO-IBD is increasing in incidence
and is associated with more severe disease, aggressive progression and poor
response to most conventional therapies. This article will review the advances in
sequencing technology that have led to identification of novel gene variants
associated with disease and potentially new targeted therapeutic options.
SUMMARY: Children with VEO-IBD may present with a different phenotype and more
severe disease than older children and adults. Identification of the causal gene
or pathways, these children may allow for true precision medicine with targeted
therapy and improved disease course.
PMID- 28700416
TI - Mandatory influenza vaccination for all healthcare personnel: a review on
justification, implementation and effectiveness.
AB - PURPOSE OF REVIEW: As healthcare-associated influenza is a serious public health
concern, this review examines legal and ethical arguments supporting mandatory
influenza vaccination policies for healthcare personnel, implementation issues
and evidence of effectiveness. RECENT FINDINGS: Spread of influenza from
healthcare personnel to patients can result in severe harm or death. Although
most healthcare personnel believe that they should be vaccinated against seasonal
influenza, the Centers for Disease Control and Prevention (CDC) report that only
79% of personnel were vaccinated during the 2015-2016 season. Vaccination rates
were as low as 44.9% in institutions that did not promote or offer the vaccine,
compared with rates of more than 90% in institutions with mandatory vaccination
policies. Policies that mandate influenza vaccination for healthcare personnel
have legal and ethical justifications. Implementing such policies require
multipronged approaches that include education efforts, easy access to vaccines,
vaccine promotion, leadership support and consistent communication emphasizing
patient safety. SUMMARY: Mandatory influenza vaccination for healthcare personnel
is a necessary step in protecting patients. Patients who interact with healthcare
personnel are often at an elevated risk of complications from influenza.
Vaccination is the best available strategy for protecting against influenza and
evidence shows that institutional policies and state laws can effectively
increase healthcare personnel vaccination rates, decreasing the risk of
transmission in healthcare settings. There are legal and ethical precedents for
institutional mandatory influenza policies and state laws, although successful
implementation requires addressing both administrative and attitudinal barriers.
PMID- 28700418
TI - Advances in paediatric cardiology 2017: the genetics of paediatric cardiovascular
disease.
PMID- 28700417
TI - Genetics of paediatric cardiomyopathies.
AB - PURPOSE OF REVIEW: Paediatric cardiomyopathy is a rare disease with a genetic
basis. The purpose of this review is to discuss the current status of genetic
findings in the paediatric cardiomyopathy population and present recent progress
in utilizing this information for management and therapy. RECENT FINDINGS: With
increased clinical genetic testing, an understanding of the genetic causes of
cardiomyopathy is improving and novel causes are identified at a rapid rate.
Recent progress in identifying the scope of genetic variation in large population
datasets has led to reassessment and refinement of our understanding of the
significance of rare genetic variation. As a result, the stringency of variant
interpretation has increased, at times leading to revision of previous mutation
results. Transcriptome and epigenome studies are elucidating important pathways
for disease progression and highlight similarities and differences in
pathogenesis from adult cardiomyopathy. Therapy targeted towards the underlying
cause of cardiomyopathy is emerging for a number of rare syndromes such as Pompe
and Noonan syndromes, and genome editing and induced pluripotent stem cells
provide promise for additional precision medicine approaches. SUMMARY: Genetics
is moving at a rapid pace in paediatric cardiomyopathy. Genetic testing is
increasingly being incorporated into clinical care. Although interpretation of
rare genetic variation remains challenging, the opportunity to provide management
and therapy targeted towards the underlying genetic cause is beginning to be
realized.
PMID- 28700419
TI - Planned Foveal Detachment Technique for the Resolution of Diabetic Macular Edema
Resistant to Anti-Vascular Endothelial Growth Factor Therapy.
PMID- 28700420
TI - COMPARISON OF 2D AND 3D VIDEO DISPLAYS FOR TEACHING VITREORETINAL SURGERY.
AB - PURPOSE: To compare medical students' learning uptake and understanding of
vitreoretinal surgeries by watching either 2D or 3D video recordings. METHODS:
Three vitreoretinal procedures (tractional retinal detachment, exposed scleral
buckle removal, and four-point scleral fixation of an intraocular lens [TSS])
were recorded simultaneously with a conventional recorder for two-dimensional
viewing and a VERION 3D HD system using Sony HVO-1000MD for three-dimensional
viewing. Two videos of each surgery, one 2D and the other 3D, were edited to have
the same content side by side. One hundred UMass medical students randomly
assigned to a 2D group or 3D, then watched corresponding videos on a MacBook. All
groups wore BiAL Red-blue 3D glasses and were appropriately randomized. Students
filled out questionnaires about surgical steps or anatomical relationships of the
pathologies or tissues, and their answers were compared. RESULTS: There was no
significant difference in comprehension between the two groups for the
extraocular scleral buckle procedure. However, for the intraocular TSS and
tractional retinal detachment videos, the 3D group performed better than 2D (P <
0.05) on anatomy comprehension questions. CONCLUSION: Three-dimensional videos
may have value in teaching intraocular ophthalmic surgeries. Surgical procedure
steps and basic ocular anatomy may have to be reviewed to ensure maximal teaching
efficacy.
PMID- 28700421
TI - Atypical Proliferative (Borderline) Serous Tumor in the Brain: A Case Report.
AB - A 59-year-old woman with a remote history of invasive ductal carcinoma of the
breast was found on a follow-up computed tomography scan of her brain to have a 1
cm lesion in the right frontal lobe in 2008. In the ensuing years, before her
current admission, multiple imaging studies of the brain revealed that the lesion
was stable and it was, therefore, interpreted as a small area of encephalomalacia
related to a thrombosed cortical vein, a cavernoma, or treated metastatic breast
cancer. In 2013, the patient underwent a bilateral salpingo-oophorectomy for
ovarian tumors that were diagnosed as bilateral serous cystadenofibromas. A
partial omentectomy showed no evidence of implants. In June 2016, the brain
lesion was completely excised and diagnosed as an atypical proliferative
(borderline) serous tumor. Immunohistochemical staining demonstrated that the
tumor cells were immunoreactive for Pax8, WT-1, ER, and CK-7 and negative for
Gata-3, PR, TTF-1, CDX-2, Napsin A, and CK-20, which was consistent with that
diagnosis. We present a brief review of possible mechanisms to account for this
unusual presentation and speculate that the most likely one is exfoliation of
fallopian tube epithelial cells into the peritoneal cavity, which then gain
access to lymphatics resulting in cells implanting in the brain and subsequently
progressing to an atypical proliferative (borderline) serous tumor.
PMID- 28700422
TI - Cervical Squamous Carcinomas With Prominent Acantholysis and Areas Resembling
Breast Lobular Carcinoma: An Aggressive Form of Dedifferentation.
AB - There have been occasional reports of primary cervical adenocarcinoma with areas
of dedifferentiation resulting in morphologic mimicry of breast lobular
carcinoma. We describe 4 cases of primary cervical squamous carcinoma with
prominent acantholysis (3 cases), areas resembling breast lobular carcinoma (3
cases) or both (2 cases). All 4 tumors showed positivity with p63 and CK5/6 and 3
of 4 exhibited block-type immunoreactivity with p16. Two of the 4 cases contained
high-risk human papillomavirus (types 16 and 18) on molecular testing; of the 2
cases which were human papillomavirus negative, 1 exhibited patchy nonblock
immunoreactivity with p16. All cases exhibited some degree of loss of E-cadherin
membranous staining in the areas of acantholysis and foci resembling breast
lobular carcinoma. Three of 4 patients had extracervical spread at diagnosis; the
fourth patient developed extracervical recurrence on follow-up. The initial FIGO
stages were IB1, IIB (2 cases) and IVB. The 2 patients whose neoplasms were human
papillomavirus negative developed distant metastases (supraclavicular, meningeal,
and lung) during the course of their disease; the same 2 patients died of disease
at periods of 4 mo and 1 yr after diagnosis. Cervical squamous carcinomas with
acantholytic features and areas resembling breast lobular carcinoma are an
unusual morphologic variant of squamous carcinoma. We consider the acantholysis
and mimicry of breast lobular carcinoma to be part of a spectrum of morphologic
changes, possibly related to loss of E-cadherin. These features can be regarded
as a form of dedifferentiation which indicates a potential for aggressive
behavior.
PMID- 28700423
TI - SOX2 Gene Amplification and Overexpression is Linked to HPV-positive Vulvar
Carcinomas.
AB - SOX2 (SRY-related HMG-box 2) belongs to the SOX gene family of high-mobility
transcription factors indispensably involved in gene regulation in pluripotent
stem cells and neural differentiation. SOX2 copy number increases have been
frequently reported in various types of squamous cell cancer. To better
understand the effect of SOX2 aberrations on vulvar cancer phenotype and patient
prognosis, we analyzed SOX2 copy number changes using fluorescence in situ
hybridization and SOX2 expression by immunohistochemistry in 55 squamous cell
carcinomas of the vulva. SOX2 amplification was found in 20.8% of tumors; 27.3%
of vulvar carcinomas showed SOX2 protein overexpression. SOX2 amplification was
correlated with SOX2 overexpression in our data set (P<0.01). Amplification of
the SOX2 locus was associated with high tumor grade (P<0.05) and human
papillomavirus (HPV) positivity (P<0.01). SOX2-amplified tumors showed more
frequently a basaloid phenotype than nonamplified carcinomas. SOX2 protein
overexpression was also correlated with basaloid phenotype and positive HPV
status of vulvar carcinomas (P<0.05, each). SOX2 amplification and expression
were not associated with patient overall survival. In conclusion, SOX2 copy
number increases are detectable in a substantial proportion of high-grade HPV
positive vulvar carcinomas with basaloid differentiation. Our study provides
further evidence for different molecular alterations in HPV-positive and HPV
negative vulvar carcinomas.
PMID- 28700424
TI - Uterine Carcinosarcomas: Clinical, Histopathologic and Immunohistochemical
Characteristics.
AB - Carcinosarcomas (malignant mixed Mullerian tumors or MMMT) are rare malignant
tumors in the female genital tract composed of both malignant epithelial and
malignant mesenchymal components. They comprise <5% of all neoplasms in the
gynecologic tract and have an aggressive clinical course. The purpose of this
study is to evaluate the immunophenotype and possible histogenesis of
carcinosarcomas of the uterus. Sixty-two cases of uterine carcinosarcomas
diagnosed between 1995 and 2011 were retrieved from the gynecologic pathology
files at Columbia University Medical Center. Representative tissue blocks
containing both epithelial and mesenchymal components were selected from each
case for histologic and immunohistochemical studies. Clinical data from each case
were retrieved. The epithelial component was poorly differentiated adenocarcinoma
in the majority (80.7%) of cases; in 17.7%, the carcinoma was moderately
differentiated, and in only 1.6% the carcinoma was well differentiated. 53% of
the tumors had homologous stromal elements and 47% displayed heterologous stromal
elements. Immunohistochemical study revealed almost equal staining in both
epithelial and mesenchymal components of carcinosarcomas for p16 and p53. PAX8
positivity was noted in 73% of epithelial components, but only 13% of stromal
components, and PAX8 stromal positivity was never seen in the absence of PAX8
epithelial positivity. Expression of p16, p53, and PAX8 in both malignant
components lends support to the monoclonal theory of uterine carcinosarcoma
tumorigenesis. The roles of these tumor markers in the diagnosis and pathogenesis
of this tumor and associations between clinical characteristics, tumor pathologic
features, and prognosis are discussed.
PMID- 28700425
TI - Ultrastaging of Sentinel Lymph Nodes in Endometrial Carcinoma According to Use of
2 Different Methods.
AB - Sentinel lymph node (SLN) sampling may provide staging information without
exposing patients to risks of lymph node dissection. There is no consensus
protocol for optimal pathologic handling of these specimens. This study compares
2 ultrastaging protocols of SLN in endometrial carcinoma (EC). All SLN were
serially sectioned perpendicular to the long axis in 2 mm intervals and entirely
submitted for routine hematoxylin and eosin (H&E) processing. SLN negative by
routine processing had ultrastaging (US) by one of the following: method 1 (M1),
5 H&E levels at 250 MUm intervals with 2 unstained slides at each level;
pankeratin immunohistochemistry (IHC) performed on level 1 in cases with negative
H&E levels or method 2 (M2), 1 H&E level + 2 unstained slides cut 250 MUm into
the tissue block; pankeratin IHC performed in cases with negative H&E. Histologic
subtype, numbers of SLN, positive SLN, non-SLN, positive non-SLN, and metastasis
size were recorded. A total of 178 patients had 527 SLNs (1-16 per case; median,
2 SLN) sampled during hysterectomy for the following EC histotypes: endometrioid
International Federation of Gynecology and Obstetrics grade 1/2, 117 (66%);
endometrioid International Federation of Gynecology and Obstetrics grade 3, 18
(10%); serous, 20 (11%); carcinosarcoma, 11 (6%); clear cell, 9 (5%); and
undifferentiated, 3 (2%). In all, 172 patients had ultrastaging: M1=65; M2=58. In
total, 33 patients were SLN positive. Twenty-seven had SLN submitted for US:
M1=11; M2=16. Eleven patients had additional SLN detected by US: M1=5; M2=6. Of
these, 8 were patients whose SLN were only detected by US representing an
increase of 32% in number of patients with positive SLN. Six patients (M1=2;
M2=4) with negative SLN had a positive non-SLN. Mean size of ultrastage-detected
metastasis was 0.24 mm for M1 and 0.38 mm for M2. Statistical analysis comparing
M1 and M2 detected no statistically significant associations with respect to
number of positive SLN detected, size of metastasis or false-negative rate and
method. The methods performed similarly for both low-grade and high-grade EC. A
more comprehensive US protocol had no significant advantages over a single wide
interval and IHC in this study population. A pankeratin IHC stain enhances
metastasis detection. Additional studies are required to further test this
limited protocol as well as to evaluate the clinical significance of the low
volume disease detected by ultrastaging.
PMID- 28700426
TI - Coexisting Primary Ovarian and Omental Hydatid Disease Mimicking an Ovarian
Neoplasm: A Case Report.
AB - Hydatid disease is a parasitic infection that most commonly affects the liver and
lungs, although the disease can arise in any part of the body. Cysts may mimic
many benign and malignant conditions. The diagnosis cannot be confirmed
preoperatively in all cases. A 44-yr-old menopausal woman was admitted to the
department of gynecology with complaints of abdominal distention. A fixed
abdominopelvic mass was identified. Radiology revealed a 20-cm mass with branched
septations and solid components. CA-125 level was 55 kU/L, and Risk of Malignancy
Index-2 score was 880. These findings suggested the presence of an ovarian
neoplasm, and laparotomy was performed. Cystic masses measuring 22 cm and 4 cm,
originating from the omentum majus and left ovary, respectively, were found
during surgery. Frozen-section analysis revealed hydatid disease. Infracolic
omentectomy and total abdominal hysterectomy with bilateral salpingo-oopherectomy
were performed. Results of a serum Echinococcus hemagglutination test performed
immediately after surgery were negative. The patient was prescribed albendazole
for 6 mo and discharged on the third postoperative day with no complaints. The
incidence of hydatid disease in the female reproductive system is very rare;
however, clinicians must be aware of this disease and take necessary precautions
while operating because any spillage may lead to anaphylactic shock and increased
risk of recurrence.
PMID- 28700427
TI - A Patient With a Low-grade Mucinous Neoplasm Involving the Ovary and Pseudomyxoma
Peritonei Originating in an Isolated Intestinal Duplication.
AB - A considerable number of mucinous ovarian tumors are metastatic from other
primary tumors, mainly from the gastrointestinal tract, and primary malignant
mucinous ovarian tumors are considered rare. Mucinous ovarian tumors occurring
within the clinical syndrome of pseudomyxoma peritonei are assumed to almost
always originate from the appendix. We describe a patient with a low-grade
mucinous tumor involving the ovary in coexistence with pseudomyxoma peritonei,
who underwent appendectomy 25 yr earlier. The tumor originated from a rare cystic
gastrointestinal duplication found in the mesenteric fat showing adenomatous
changes. This illustrates that even in absence of the appendix, mucinous ovarian
tumors occurring with pseudomyoma peritonei rarely arise from the ovary.
PMID- 28700428
TI - Prospective Evaluation of Lymph Node Processing at Staging Surgery for High-grade
Endometrial Cancer.
AB - To determine whether the processing of additional adipose tissue collected during
lymph node (LN) dissection results in the identification of additional LNs during
endometrial cancer (EC) staging and to determine if the division of LNs into
nodal basin-specific specimens has an effect on the number of LNs identified
during EC staging. A prospective randomized controlled trial was performed on
women with high-grade EC undergoing surgical staging. Subjects were randomized to
collection of LNs into nodal basin-specific containers on the randomized side
versus simple labeling on the nonrandomized side. The total number of LNs and
total number of LNs with metastases on the randomized versus the nonrandomized
side were compared. The remaining adipose tissue from each LN specimen was
submitted for histologic examination. We analyzed the number of LNs with and
without metastases identified from additional adipose tissue. Of 120 consented
subjects, 56 had sufficient data for analysis. The additional adipose tissue
contained 7.5 additional LNs per patient on average (range: 0-26). In 2/54 total
cases (3.7%) and 2/5 cases with nodal metastases (40%), the additional adipose
contained LNs with metastases. In both cases, metastases were also detected in
grossly identified LN candidates. The mean number of LNs identified was not
significantly different based on method of collection (P=0.22). The mean number
of LNs containing metastases per side was not significantly different (P=0.58).
Processing of adipose tissue does increase the total number of LNs identified,
however, it does not influence EC stage. No difference in LN counts was noted
with basin-specific collection.
PMID- 28700429
TI - Mucosal Proliferations in Completely Examined Fallopian Tubes Accompanying
Ovarian Low-grade Serous Tumors: Neoplastic Precursor Lesions or Normal Variants
of Benign Mucosa?
AB - Malignant transformation of the fallopian tube mucosa, followed by exfoliation of
malignant cells onto ovarian and/or peritoneal surfaces, has been implicated as
the origin of most pelvic high-grade serous carcinoma. Whether a parallel pathway
exists for pelvic low-grade serous tumors [ovarian serous borderline tumor (SBT)
and low-grade serous carcinoma (LGSC)] remains to be fully elucidated. The
literature is challenging to interpret due to variation in the diagnostic
criteria and terminology for cytologically low-grade proliferations of the
fallopian tube mucosa, as well as variation in fallopian tube specimen sampling.
Recently, a candidate fallopian tube precursor to ovarian SBT, so-called
papillary tubal hyperplasia, was described in advanced stage patients. The
current study was designed to identify fallopian tube mucosal proliferations
unique to patients with low-grade serous ovarian tumors (serous cystadenoma, SBT,
LGSC) and to determine if they may represent precursors to the ovarian tumors.
Fallopian tubes were thinly sliced and entirely examined microscopically,
including all of the fimbriated and nonfimbriated portions of the tubes, from
patients with ovarian serous cystadenoma (35), SBT (61), and LGSC (11) and from a
control population of patients with ovarian mucinous cystadenoma (28), mature
cystic teratoma (18) or uterine leiomyoma (14). The slides of the fallopian tubes
were examined in randomized order, without knowledge of the clinical history or
findings in the ovaries or other organs. Alterations of the mucosa of the
fallopian tube were classified as type 1: nonpapillary proliferation of
cytologically bland tubal epithelium exhibiting crowding, stratification, and/or
tufting without papillary fibrovascular cores or as type 2: papillary alterations
consisting of a fibrovascular core lined by a cytologically bland layer of tubal
epithelium. A third abnormality, type 3, consisted of detached intraluminal
papillae, buds, or nests of epithelium that cytologically resembled the
epithelial component of SBT or LGSC. Mucosal proliferations were identified in
subsets of all populations, including the control populations. Overall, type 1
proliferations were in 28% to 61% of all patients and type 2 alterations in 4% to
16%. There was no statistically significant difference in the incidence of type 1
or type 2 proliferations between the class of ovarian serous tumors (benign, SBT,
LGSC), between early and advanced stage SBT, or between patients with any ovarian
serous tumor and the control population of nonserous diagnoses. Type 3
alterations were only identified in patients with advanced stage SBT/LGSC and not
in any early stage SBT or cystadenoma. These findings suggest that type 3
alterations floating in the fallopian tube lumen represent exfoliation of tumor
cells from ovarian and/or peritoneal origin. Our study did not identify a mucosal
based proliferation of the fallopian tubes that was specific to ovarian low-grade
serous tumors. Cytologically bland mucosal proliferations appear to be common in
fallopian tubes from patients of all ages and unrelated to ovarian tumorigenesis.
A consensus on diagnostic criteria and terminology for these types of
proliferations is needed, as well as further study into their etiology, including
possible association with hormonal environment.
PMID- 28700430
TI - Epidermodysplasia Verruciformis-like HPV Infection of the Vulva in
Immunosuppressed Women.
AB - The vast majority of vulvar human papilloma virus infections are produced by
alpha human papilloma viruses and consist of exophytic or flat warts and classic
or "usual" vulvar intraepithelial neoplasia. This report details 2 examples of
epidermodysplasia verruciformis-like lesions of the vulva in women who were
immunosuppressed. The most consistent morphologic feature was the presence of
abnormal mature keratinocytes with large pale open nuclei with small nucleoli and
eosinophilic cytoplasm, situated in the upper epithelial layers. In addition to
these features, which are commonly seen in epidermodysplasia verruciformis
associated lesions, 1 case displayed in addition more extensively distributed
abnormal nuclei, including involvement of both the upper epithelial strata and
the epithelial/stromal interface. Both lesions were associated with beta
papilloma virus type 5. The unique aspects of epidermodysplasia verruciformis
like lesions relative to the more common human papilloma virus infections of the
vulva are highlighted and these cases illustrate the range of epithelial
distribution that might be encountered in lesions involving the vulvar mucosa.
PMID- 28700431
TI - Methods for Measuring and Staging a Uterine Cervical Adenocarcinoma Showing
Intracystic Papillary Growth: A Case Report.
AB - Endocervical adenocarcinomas usually demonstrate infiltrative and/or destructive
invasion, and the depth and horizontal extent of the invasion are known to have
prognostic utility. Here, we report the unusual case of a patient with
endocervical adenocarcinoma showing intracystic papillary growth and discuss our
methods for measuring and staging this lesion. A 45-yr-old Japanese woman
(gravida, 0; para, 0) underwent a cone biopsy for squamous cell carcinoma in situ
and atypical glandular cells. Macroscopically, an intracystic tumor (~7.5 mm in
diameter) was detected in the cervix. Microscopically, we observed both squamous
cell carcinoma in situ and adenocarcinoma involving the squamo-columnar junction.
Adenocarcinoma cells lining the nabothian cyst showed papillary proliferation and
expansile stromal invasion without desmoplastic reaction. We evaluated this
macroscopically and found that the visible papillary growth and expansile
invasion deviated from the adenocarcinoma in situ; hence, we concluded that this
lesion was an International Federation of Gynecology and Obstetrics stage IB1
adenocarcinoma. The patient underwent an abdominal radical hysterectomy, followed
by bilateral salpingo-oophorectomy and pelvic lymph node dissection. No residual
cervical cancer, other gynecologic malignancies, or lymph node metastases were
observed. Further studies using cases with the same growth pattern are needed to
determine whether our evaluation method is optimal for this type of lesion.
PMID- 28700432
TI - Novel Fumarate Hydratase Mutation in Siblings With Early Onset Uterine Leiomyomas
and Hereditary Leiomyomatosis and Renal Cell Cancer Syndrome.
AB - Hereditary leiomyomatosis renal cell cancer syndrome is an autosomal dominant
disorder characterized by uterine and cutaneous leiomyomas and increased
predisposition to renal cell carcinoma, papillary type II. The syndrome is caused
by heterozygous mutations to the fumarate hydratase (FH) gene located on
chromosome 1. Affected females generally present with early onset, atypical
uterine leiomyomas and cutaneous findings, however, delays in diagnosis are very
common in patients with isolated uterine findings. We present a case series of 2
sisters in their 20s who presented with isolated uterine leiomyomas and were
found to carry a novel mutation for the fumarate hydratase gene. One patient was
referred for treatment of infertility and recurrent miscarriages and the other
was referred for acute symptomatic anemia due to myomas. Prompt diagnosis of
hereditary leiomyomatosis renal cell cancer was made due to a high index of
clinical suspicion based on early onset disease and familial clustering as well
as characteristic pathologic findings on uterine leiomyoma surgical specimen.
Timely diagnosis not only allowed for genetic counseling and renal cancer
surveillance, but also for fertility counseling given the increased morbidity
associated with uterine leiomyoma due to hereditary leiomyomatosis and renal cell
cancer syndrome.
PMID- 28700433
TI - Data Set for the Reporting of Carcinomas of the Cervix: Recommendations From the
International Collaboration on Cancer Reporting (ICCR).
AB - A comprehensive pathologic report is essential for optimal patient management,
cancer staging and prognostication. In many countries, proforma reports are used
but the content of these is variable. The International Collaboration on Cancer
Reporting is an alliance formed by the Royal Colleges of Pathologists of
Australasia and the United Kingdom, the College of American Pathologists, the
Canadian Partnership Against Cancer and the European Society of Pathology, for
the purpose of developing standardized, evidence-based reporting data sets for
each cancer site. This will reduce the global burden of cancer data set
development and reduplication of effort by different international institutions
that commission, publish and maintain standardized cancer-reporting data sets.
The resultant standardization of cancer-reporting benefits not only those
countries directly involved in the collaboration but also others not in a
position to develop their own data sets. We describe the development of an
evidence-based cancer data set by the International Collaboration on Cancer
Reporting expert panel for the reporting of primary cervical carcinomas and
present the "required" and "recommended" elements to be included in the pathology
report as well as an explanatory commentary. This data set encompasses the
International Federation of Obstetricians and Gynaecologists and Union for
International Cancer Control staging systems for cervical neoplasms and the
updated World Health Organization classification of gynecologic tumors. The data
set also addresses controversial issues such as tumor grading and measurement,
including measurement of multifocal carcinomas. The widespread implementation of
this data set will facilitate consistent and accurate data collection, comparison
of epidemiological and pathologic parameters between different populations,
facilitate research, and hopefully result in improved patient management.
PMID- 28700434
TI - Comparison of p63 and p40 Immunohistochemical Stains to Distinguish Epithelioid
Trophoblastic Tumor From Other Trophoblastic Lesions.
PMID- 28700435
TI - IFITM1 Outperforms CD10 in Differentiating Low-grade Endometrial Stromal Sarcomas
From Smooth Muscle Neoplasms of the Uterus.
AB - Distinguishing between uterine neoplasms of smooth muscle and endometrial stromal
origin is a frequent diagnostic challenge. We investigated the staining pattern
of interferon-induced transmembrane protein-1 (IFITM1), a novel endometrial
stromal marker, in endometrial and smooth muscle uterine neoplasms and compared
it with CD10 in its ability to differentiate between these two groups.
Immunohistochemistry for IFITM1 and CD10 was performed in 20 cases of smooth
muscle neoplasms (10 cases leiomyoma, 10 cases leiomyosarcoma), 14 cases of
endometrial stromal sarcoma (ESS) (12 cases of low grade and 2 cases of high
grade) and 12 cases of carcinosarcoma. Staining was scored in terms of intensity
and distribution (0=absent, 1=weak/<50%, 2=moderate/50%-75%, 3=strong/>75%). A
total score was obtained by adding intensity and distribution scores and
classified as positive (score 3-6) or negative (score 0-2). IFITM1 was positive
in 10 of 12 (83%) low-grade ESSs, 6 of 20 (30%) smooth muscle tumors (leiomyomas
and leiomyosarcomas) and 11 of 12 carcinosarcomas (91.6%). The 2 cases of high
grade ESS were IFITM1 negative. While both IFITM1 (83%) and CD10 (91%) had high
sensitivity in differentiating low-grade ESSs from smooth muscle neoplasms,
IFITM1 (70%) had higher specificity compared with CD10 (45%). In this study
IFITM1 appears to be a more specific marker of endometrial stromal
differentiation compared with CD10 in differentiating low-grade ESSs from smooth
muscle neoplasms. Thus, IFITM1 may be a valuable tool as part of an
immunohistochemical evaluation panel in this diagnostic scenario.
PMID- 28700436
TI - Malignant Female Adnexal Tumor of Probable Wolffian Origin: Case Report and
Literature Review.
AB - Although most female adnexal tumors of probable Wolffian origin have a benign
biologic behavior, occasional cases have exhibited malignant potential. We
encountered a 50-yr-old woman with an uncommon female adnexal tumors of probable
Wolffian origin, which involved bilateral ovaries, invaded the ipsilateral
fallopian tube, and extended to the uterine serosa. The initial histopathologic
presentation caused significant confusion in pathologic diagnosis. Multiple
differential diagnoses including ovarian endometrioid carcinoma, Sertoli cell
tumor, and metastasis from nongynecologic organs were considered. After careful
examination of the histologic findings and a thorough investigation with multiple
immunohistochemical stains, the diagnosis was ultimately established. A
literature review on female adnexal tumors of probable Wolffian origin including
a malignant form is presented.
PMID- 28700437
TI - Adenomyoma With Pseudoinvasive Growth Pattern and Serosal Penetration Mimicking
Endometrial Carcinoma.
AB - We present a novel case of a 48-yr-old female with a uterine adenomyoma with an
unusual pseudoinvasive growth pattern displaying full-thickness penetration
beyond the serosal surface in association with a dehisced Caesarian scar. Before
hysterectomy, magnetic resonance imaging findings showed an infiltrative lesion
suggestive of endometrial carcinoma. An endometrial biopsy was benign but
definitive operative management was pursued given the concerning imaging. Gross
examination of the uterus demonstrated a 7.2 cm, relatively well-circumscribed
polypoid neoplasm with pushing borders extending through the full thickness of
the myometrium. A serosal defect with protruding red tissue was noted where the
neoplasm penetrated the exterior surface of the uterus. Histologic examination
demonstrated benign endometrial glands, associated endometrial stroma, thick
walled vessels, and a prominent smooth muscle component consistent with an
adenomyoma. To our knowledge, this unique presentation of a pseudoinvasive
adenomyoma extending beyond the serosa is extremely rare and is the first time
reported in the literature.
PMID- 28700438
TI - FOXL2 Mutation Analysis of Ovarian Sex Cord-Stromal Tumors: Genotype-Phenotype
Correlation With Diagnostic Considerations.
AB - Correlation of FOXL2 mutation status with morphologic features and reticulin
staining patterns was performed in a comprehensive single-institutional cohort of
ovarian sex cord-stromal tumors. Fifty-one cases were included, 35 of which were
morphologically diagnosed as adult granulosa cell tumor, 4 as Sertoli-Leydig cell
tumor, 11 as fibroma/fibrothecoma and 1 as a thecoma. Of the adult granulosa cell
tumors, 31 (88.6%) harbored FOXL2 mutation. Abundant pale cytoplasm was seen in
51.6% (16/31) of FOXL2 mutated tumors, compared with 6.7% (1/15) among FOXL2 wild
type tumors (P=0.003). Nearly half of FOXL2 negative tumors showed individual
pericellular reticulin staining pattern, while none of the FOXL2 positive cases
demonstrated this feature (P=0.0001). Nested reticulin pattern was observed in
67.7% of FOXL2 positive tumors, compared with 20% of FOXL2 negative cases
(P=0.004). Indeterminate reticulin staining pattern was seen in nearly one third
of cases in both groups. Nested reticulin pattern was 87.5% specific and 67.7%
sensitive for FOXL2 mutation, while individual reticulin pattern was 100%
specific for absence of FOXL2 mutation. No statistical significance was observed
between the 2 groups in tumor size, mitotic activity, nuclear atypia, and nuclear
grooves. Follow-up was available for 44 patients ranging from 0.3 to 259 months
(mean: 67.5 mo). Two patients developed recurrence, both of them harbored FOXL2
mutation. In conclusion, the pathology diagnosis of sex cord-stromal tumors
continues to be difficult, and reticulin staining remains a valuable tool as an
initial step in the diagnostic work-up. Individual pericellular reticulin pattern
essentially rules out adult granulosa cell tumor, while cases with indeterminate
or nested patterns can be subjected to FOXL2 mutation testing to aid the
diagnosis.
PMID- 28700439
TI - Genital Rhabdomyoma of the Lower Female Genital Tract: A Study of 12 Cases With
Molecular Cytogenetic Findings.
AB - Of the subtypes of extracardiac rhabdomyoma, genital rhabdomyoma is most uncommon
and is occasionally classified as fetal rhabdomyoma due to morphologic
similarities. In contrast to other forms of rhabdomyoma, the genetic alterations
of genital rhabdomyoma are unknown. The clinical and pathologic findings in 12
cases were reviewed and 2 cases were processed for whole genome copy number
analysis by single nucleotide polymorphism microarray. Twelve patients ranged in
age from 43 to 65 yr (mean: 50.2 yr). Nine tumors arose in the vagina and 3 in
the cervix, with their greatest dimension spanning 0.9 to 1.7 cm (mean: 1.4 cm).
Follow-up was available for 7 patients and none had evidence of recurrence (67
263 mo, mean: 153.7 mo). No somatic copy number alterations, particularly
involving genes in Hedgehog signaling, were identified by microarray. Although
genital rhabdomyoma has sufficiently unique clinicopathologic characteristics
including age of onset and organs of involvement to distinguish it from fetal
rhabdomyoma, the genetic mechanisms underlying its development are unclear given
the lack of copy number variation and loss of heterozygosity by single nucleotide
polymorphism microarray.
PMID- 28700440
TI - De Novo Tumors of Teratoma: Ganglioneuroma Arising From a Mature Cystic Teratoma
of the Ovary.
AB - Mature teratomas are the most common ovarian neoplasms, accounting for 40% to 50%
of ovarian tumors, and are histologically defined by the presence of multiple
lineages of mature differentiated cells derived from one or more of the 3
embryonic germ layers; ectoderm, mesoderm, and endoderm. Neuroectodermal and
neural crest differentiation can be observed in mature teratomas, but it is
uncommon to find secondary tumors that arise from the neural crest lineage.
Herein we report the uncommon finding of a ganglioneuroma arising in a mature
cystic teratoma in a 26-yr-old woman.
PMID- 28700441
TI - Leiomyoma With Bizarre Nuclei: Clinical and Pathologic Features of 30 Patients.
AB - Leiomyoma with bizarre nuclei (LBN) have significant cytologic atypia, but high
mitotic rate and tumor cell necrosis are absent. Although it is a benign
leiomyoma variant, recurrent cases have been described. In this study, we
investigated the clinical and pathologic features of LBN and compared them with
related studies. A total of 30 patients diagnosed with LBN in our department were
included in this study. In all cases, clinical data (age, complaint, surgery
type), macroscopic features (size, location, number of leiomyomas, necrosis, and
hemorrhage), microscopic features (bizarre cell distribution, bizarre cell
density, cellularity, mitotic rate, tumor margin, necrosis, nuclear
pseudoinclusions, karyorrhectic nuclei, prominent eosinophilic nucleoli with
perinucleolar clearing, cytoplasmic eosinophilic inclusions, staghorn vessels,
and alveolar-type edema), and follow-up data (recurrence and survival period)
were evaluated. The mean age of the patients was 49.76 yr (range: 38-89 yr).
Twenty-two patients (73%) had undergone hysterectomy and 8 patients (27%) had
undergone myomectomy. The mean tumor diameter was 6.12 cm (range: 0.5-25 cm). The
tumor was intramural in 11 patients (37%), subserosal in 7 patients (23%), and
submucosal in 4 patients (13%). Microscopically, the bizarre cell distribution
was focal in 8 patients (27%), multifocal in 12 patients (40%), and diffuse in 10
patients (33%). Bizarre cell density was low in 15 patients (50%), intermediate
in 8 patients (27%), and high in 7 patients (23%). The mean mitotic count was 1.4
(0-4) in 10 high-power fields, and the tumor margin was regular in all cases. We
observed pseudoinclusions in 24 of 30 (80%) tumors, karyorrhectic nuclei in 21 of
30 tumors (70%), prominent eosinophilic nucleoli with perinucleolar clearing in
12 tumors (40%), cytoplasmic eosinophilic inclusions in 11 tumors (37%), staghorn
vessels in 9 tumors (30%), and alveolar-type edema in 9 tumors (30%). In
addition, we examined the follow-up records of 26 patients (average duration:
58.1 mo). One patient had a smooth muscle tumor in the L3-L4 paravertebral region
at 67 mo after hysterectomy. This tumor did not share similar microscopic and
immunohistochemical findings to the patient's earlier uterine tumor. The
definitive diagnosis of uterine smooth muscle tumors is important for the
determination of the prognosis of the patient and the most appropriate
therapeutic approach. As in several recent studies, our series has shown that LBN
has a benign clinical course. However, other malignant morphologic criteria such
as high mitotic rate and tumor cell necrosis should be excluded in the diagnosis
of LBN.
PMID- 28700442
TI - Hospital-level Variation in Utilization of Surgery for Clinical Stage I-II
Pancreatic Adenocarcinoma.
AB - OBJECTIVE: To (1) evaluate rates of surgery for clinical stage I-II pancreatic
ductal adenocarcinoma (PDAC), (2) identify predictors of not undergoing surgery,
(3) quantify the degree to which patient- and hospital-level factors explain
differences in hospital surgery rates, and (4) evaluate the association between
adjusted hospital-specific surgery rates and overall survival (OS) of patients
treated at different hospitals. BACKGROUND: Curative-intent surgery for
potentially resectable PDAC is underutilized in the United States. METHODS:
Retrospective cohort study of patients <=85 years with clinical stage I-II PDAC
in the 2004 to 2014 National Cancer Database. Mixed effects multivariable models
were used to characterize hospital-level variation across quintiles of hospital
surgery rates. Multivariable Cox proportional hazards models were used to
estimate the effect of adjusted hospital surgery rates on OS. RESULTS: Of 58,553
patients without contraindications or refusal of surgery, 63.8% underwent
surgery, and the rate decreased from 2299/3528 (65.2%) in 2004 to 4412/7092
(62.2%) in 2014 (P < 0.001). Adjusted hospital rates of surgery varied 6-fold
(11.4%-70.9%). Patients treated at hospitals with higher rates of surgery had
better unadjusted OS (median OS 10.2, 13.3, 14.2, 16.5, and 18.4 months in
quintiles 1-5, respectively, P < 0.001, log-rank). Treatment at hospitals in
lower surgery rate quintiles 1-3 was independently associated with mortality
[Hazard ratio (HR) 1.10 (1.01, 1.21), HR 1.08 (1.02, 1.15), and HR 1.09 (1.04,
1.14) for quintiles 1-3, respectively, compared with quintile 5] after adjusting
for patient factors, hospital type, and hospital volume. CONCLUSIONS: Quality
improvement efforts are needed to help hospitals with low rates of surgery ensure
that their patients have access to appropriate surgery.
PMID- 28700443
TI - Assessment of Conflicts of Interest in Robotic Surgical Studies: Validating
Author's Declarations With the Open Payments Database.
AB - BACKGROUND: Accurate conflict of interest (COI) statements are important, as a
known COI may invalidate study results due to the potential risk of bias.
OBJECTIVE: To determine the accuracy of self-declared COI statements in robotic
studies and identify risk factors for undeclared payments. METHODS: Robotic
surgery studies were identified through EMBASE and MEDLINE and included if
published in 2015 and had at least one American author. Undeclared COI were
determined by comparing the author's declared COI with industry reported payments
found in the "Open Payments" database for 2013 and 2014. Undeclared payments and
discrepancies in the COI statement were determined. Risk factors were assessed
for an association with undeclared payments at the author and study level.
RESULTS: A total of 458 studies (2253 authors) were included. Approximately, 240
(52%) studies had 1 or more author receive undeclared payments and included 183
where "no COI" was explicitly declared, and 57 with no declaration statement
present. Moreover, 21% of studies and 18% of authors with a COI declared it so in
a COI statement. Studies that had undeclared payments from Intuitive were more
likely to recommend robotic surgery compared with those that declared funding
(odds ratio 4.29, 95% confidence interval 2.55-7.21). CONCLUSIONS: We found that
it was common for payments from Intuitive to be undeclared in robotic surgery
articles. Mechanisms for accountability in COI reporting need to be put into
place by journals to achieve appropriate transparency to those reading the
journal article.
PMID- 28700444
TI - Multi-institutional Validation Study of Pancreatic Cyst Fluid Protein Analysis
for Prediction of High-risk Intraductal Papillary Mucinous Neoplasms of the
Pancreas.
AB - OBJECTIVE: Preliminary work by our group suggested that proteins within the
pancreatic cyst fluid (CF) may discriminate degree of IPMN dysplasia. We sought
to externally validate these markers and determine whether their inclusion in a
preoperative clinical nomogram could increase diagnostic accuracy. SUMMARY
BACKGROUND DATA: IPMN is the most common radiographically identifiable precursor
to pancreatic cancer; however, the timing and frequency of its malignant
progression are unknown, and there are currently no reliable preoperative tests
that can determine the grade of dysplasia in IPMN. METHODS: Clinical and
radiographic data, as well as CF samples, were obtained from 149 patients who
underwent resection for IPMN at 1 of 3 institutions. High-risk disease was
defined as the presence of high-grade dysplasia or invasive carcinoma.
Multianalyte bead array analysis (Luminex) of CF was performed for 4 protein
markers that were previously associated with high-risk disease. Logistic
regression models were fit on training data, with and without adjustment for a
previously developed clinical nomogram and validated with an external testing
set. The models incorporating clinical risk score were presented graphically as
nomograms. RESULTS: Within the group of 149 resected patients, 89 (60%) had low
risk disease, and 60 (40%) had high-risk disease. All 4 CF markers (MMP9, CA72-4,
sFASL, and IL-4) were overexpressed in patients with high-risk IPMN (P < 0.05).
Two predictive models based on preselected combinations of CF markers had
concordance indices of 0.76 (Model-1) and 0.80 (Model-2). Integration of each CF
marker model into a previously described clinical nomogram leads to increased
discrimination compared with either the CF models or nomogram alone (c-indices of
0.84 and 0.83, respectively). CONCLUSIONS: This multi-institutional study
validated 2 CF protein marker models for preoperative identification of high-risk
IPMN. When combined with a clinical nomogram, the ability to predict high-grade
dysplasia was even stronger.
PMID- 28700445
TI - Auditory Brainstem Implant Array Position Varies Widely Among Adult and Pediatric
Patients and Is Associated With Perception.
AB - OBJECTIVES: The auditory brainstem implant (ABI) provides sound awareness to
patients who are ineligible for cochlear implantation. Auditory performance
varies widely among similar ABI cohorts. We hypothesize that differences in
electrode array position contribute to this variance. Herein, we classify ABI
array position based on postoperative imaging and investigate the relationship
between position and perception. DESIGN: Retrospective review of pediatric and
adult ABI users with postoperative computed tomography. To standardize views
across subjects, true axial reformatted series of scans were created using the
McRae line. Using multiplanar reconstructions, basion and electrode array tip
coordinates and array angles from vertical were measured. From a lateral view,
array angles (V) were classified into types I to IV, and from posterior view,
array angles (T) were classified into types A to D. Array position was further
categorized by measuring distance vertical from basion (D1) and lateral from
midline (D2). Differences between array classifications were compared with
audiometric thresholds, number of active electrodes, and pitch ranking. RESULTS:
Pediatric (n = 4, 2 with revisions) and adult (n = 7) ABI subjects were included
in this study. Subjects had a wide variety of ABI array angles, but most were
aimed superiorly and posteriorly (type II, n = 7) from lateral view and upright
or medially tilted from posterior view (type A, n = 6). Mean pediatric distances
were 8 to 42% smaller than adults for D1 and D2. In subjects with perceptual
data, electrical thresholds and the number of active electrodes differed among
classification types. CONCLUSIONS: In this first study to classify ABI electrode
array orientation, array position varied widely. This variability may explain
differences in auditory performance.
PMID- 28700446
TI - Pure-Tone Masking Patterns for Monopolar and Phantom Electrical Stimulation in
Cochlear Implants.
AB - OBJECTIVES: Monopolar stimulation of the most apical electrode produces the
lowest pitch sensation in cochlear implants clinically. A phantom electrode that
uses out-of-phase electrical stimulation between the most apical and the
neighboring basal electrode can produce a lower pitch sensation than that
associated with the most apical electrode. However, because of the absence of
contacts beyond the apical tip of the array, the ability to assess the spread of
electrical excitation associated with phantom stimulation is limited in the
typical cochlear implant subject with no residual hearing. In the present study,
the spread of electrical excitation associated with monopolar and phantom
stimulation of the most apical electrode was assessed using electrical masking of
acoustic thresholds in cochlear implant subjects with residual, low-frequency,
acoustic hearing. DESIGN: Eight subjects with an Advanced Bionics cochlear
implant and residual hearing in the implanted ear participated in this study
(nine ears in total). Unmasked and masked thresholds for acoustic pure tones were
measured at 125, 250, 500, 750, 1000, and 2000 Hz in the presence of monopolar
and phantom electrode stimulation presented at the apical-most end of the array.
The current compensation for phantom electrode stimulation was fixed at 50%. The
two electrical maskers were loudness balanced. Differences between the unmasked
and masked acoustic thresholds can be attributed to (1) the electrical stimulus
induced interference in the transduction/conduction of the acoustic signal
through cochlear periphery and the auditory nerve and/or (2) masking at the level
of the central auditory system. RESULTS: The results show a significant elevation
in pure-tone thresholds in the presence of the monopolar and phantom electrical
maskers. The unmasked thresholds were subtracted from the masked thresholds to
derive masking patterns as a function of the acoustic probe frequency. The
masking patterns show that phantom stimulation was able to produce more masking
than that associated with the monopolar stimulation of the most apical electrode.
CONCLUSION: These results suggest that for some cochlear implant subjects,
phantom electrode stimulation can shift the neural stimulation pattern more
apically in the cochlea, which is consistent with reports that phantom electrode
stimulation produces lower pitch sensations than those associated with monopolar
stimulation of the most apical electrode alone.
PMID- 28700447
TI - Impact of Hearing Aid Technology on Outcomes in Daily Life III: Localization.
AB - OBJECTIVE: Compared to basic-feature hearing aids, premium-feature hearing aids
have more advanced technologies and sophisticated features. The objective of this
study was to explore the difference between premium-feature and basic-feature
hearing aids in horizontal sound localization in both laboratory and daily life
environments. We hypothesized that premium-feature hearing aids would yield
better localization performance than basic-feature hearing aids. DESIGN:
Exemplars of premium-feature and basic-feature hearing aids from two major
manufacturers were evaluated. Forty-five older adults (mean age 70.3 years) with
essentially symmetrical mild to moderate sensorineural hearing loss were
bilaterally fitted with each of the four pairs of hearing aids. Each pair of
hearing aids was worn during a 4-week field trial and then evaluated using
laboratory localization tests and a standardized questionnaire. Laboratory
localization tests were conducted in a sound-treated room with a 360 degrees , 24
loudspeaker array. Test stimuli were high frequency and low frequency filtered
short sentences. The localization test in quiet was designed to assess the
accuracy of front/back localization, while the localization test in noise was
designed to assess the accuracy of locating sound sources throughout a 360
degrees azimuth in the horizontal plane. RESULTS: Laboratory data showed that
unaided localization was not significantly different from aided localization when
all hearing aids were combined. Questionnaire data showed that aided localization
was significantly better than unaided localization in everyday situations.
Regarding the difference between premium-feature and basic-feature hearing aids,
laboratory data showed that, overall, the premium-feature hearing aids yielded
more accurate localization than the basic-feature hearing aids when high
frequency stimuli were used, and the listening environment was quiet. Otherwise,
the premium-feature and basic-feature hearing aids yielded essentially the same
performance in other laboratory tests and in daily life. The findings were
consistent for both manufacturers. CONCLUSIONS: Laboratory tests for two of six
major manufacturers showed that premium-feature hearing aids yielded better
localization performance than basic-feature hearing aids in one out of four
laboratory conditions. There was no difference between the two feature levels in
self-reported everyday localization. Effectiveness research with different
hearing aid technologies is necessary, and more research with other
manufacturers' products is needed. Furthermore, these results confirm previous
observations that research findings in laboratory conditions might not translate
to everyday life.
PMID- 28700448
TI - Linguistic Context Versus Semantic Competition in Word Recognition by Younger and
Older Adults With Cochlear Implants.
AB - OBJECTIVES: The increasing numbers of older adults now receiving cochlear
implants raises the question of how the novel signal produced by cochlear
implants may interact with cognitive aging in the recognition of words heard
spoken within a linguistic context. The objective of this study was to pit the
facilitative effects of a constraining linguistic context against a potential age
sensitive negative effect of response competition on effectiveness of word
recognition. DESIGN: Younger (n = 8; mean age = 22.5 years) and older (n = 8;
mean age = 67.5 years) adult implant recipients heard 20 target words as the
final words in sentences that manipulated the target word's probability of
occurrence within the sentence context. Data from published norms were also used
to measure response entropy, calculated as the total number of different
responses and the probability distribution of the responses suggested by the
sentence context. Sentence-final words were presented to participants using a
word-onset gating paradigm, in which a target word was presented with increasing
amounts of its onset duration in 50 msec increments until the word was correctly
identified. RESULTS: Results showed that for both younger and older adult implant
users, the amount of word-onset information needed for correct recognition of
sentence-final words was inversely proportional to their likelihood of occurrence
within the sentence context, with older adults gaining differential advantage
from the contextual constraints offered by a sentence context. On the negative
side, older adults' word recognition was differentially hampered by high response
entropy, with this effect being driven primarily by the number of competing
responses that might also fit the sentence context. CONCLUSIONS: Consistent with
previous research with normal-hearing younger and older adults, the present
results showed older adult implant users' recognition of spoken words to be
highly sensitive to linguistic context. This sensitivity, however, also resulted
in a greater degree of interference from other words that might also be activated
by the context, with negative effects on ease of word recognition. These results
are consistent with an age-related inhibition deficit extending to the domain of
semantic constraints on word recognition.
PMID- 28700449
TI - Development of a Simple and Rapid Method to Measure Free Fraction of Valproic
Acid in Plasma Using Ultrafiltration and Ultra High Performance Liquid
Chromatography-Mass Spectroscopy: Application to Therapeutic Drug Monitoring.
AB - BACKGROUND: Valproic acid (VPA) is widely used as an antiepileptic drug in
children, and it is usually coadministered with other antiepileptic drugs.
Because of its narrow therapeutic range and large variations in
pharmacokinetic/pharmacodynamic behavior in different individuals, therapeutic
drug monitoring of the trough total VPA concentration is commonly used to guide
dosing. However, as only the free fraction of VPA that exerts pharmacological and
toxic effects, it may be more meaningful to determine the unbound VPA
concentration in plasma. METHODS: Free fraction of VPA in plasma was extracted by
ultrafiltration. Ultra high performance liquid chromatography coupled with mass
spectroscopy was used to measure VPA in the negative ionization mode. This method
was validated by studies of its selectivity, linearity, lower limit of
quantification, accuracy, precision, recovery, matrix effect, and stability.
RESULTS: The method was validated over a linear range of 0.2-25 mcg/mL, and its
lower limit of quantification was 0.2 mcg/mL. The method's relative standard
deviations for intra- and inter-day precision were <15%, and its accuracy
(relative error) was +/-3.22%. The recoveries and matrix effect of unbound VPA at
3 different concentrations satisfied our requirements for the analysis of
biological samples, and no significant degradation of VPA was observed under
different storage conditions. CONCLUSIONS: Simple ultra high performance liquid
chromatography coupled with mass spectroscopy showed good performance when used
to measure unbound VPA concentration, this method may be used to study the
relationship between unbound VPA concentrations and its effectiveness by the use
of therapeutic drug monitoring.
PMID- 28700450
TI - Comparison of 30-Day Complications Between Navigated and Conventional Single
level Instrumented Posterior Lumbar Fusion: A Propensity Score Matched Analysis.
AB - STUDY DESIGN: Retrospective cohort comparison study. OBJECTIVE: To compare
perioperative outcomes between navigated and conventional single-level
instrumented posterior lumbar fusions in the American College of Surgeons
National Surgical Quality Improvement Program (NSQIP) database. SUMMARY OF
BACKGROUND DATA: Although multiple studies have investigated the accuracy of
pedicle screw placement and radiation exposure with navigation, no study has
compared perioperative complications between navigated and conventional posterior
lumbar fusion. The potential benefits of navigation include improved accuracy of
screw placement and reduced surgeon radiation exposure, but this is balanced by
potential operative time and surgical site contamination/infection related to
this bulky technology. METHODS: Patients who underwent navigated or conventional
single-level posterior instrumented lumbar fusions were identified in the 2010
2015 NSQIP database. The usage of navigation was characterized. Patient
characteristics and comorbidities were compared between the two treatment groups.
Propensity score matching was done and comparisons were made for operative time,
hospital length of stay, postoperative complications, and 30-day readmissions
between the two cohorts. RESULTS: The percentage of navigated cases tended to
increase over years studied to approximately 10%. After propensity matching to
control potential confounding factors, statistical analysis revealed no
significant difference in operative time and for most adverse events including
wound infection, return to the operating room, and readmission. There were
significantly lower blood transfusions in the navigated cohort (2.84% vs. 7.15%,
P < 0.001). Patients who underwent navigated surgery also had a shorter mean
hospital length of stay (0.2 day difference, P = 0.016). CONCLUSION: The reduced
blood loss and mildly reduced hospital length of stay identified for the
navigated cases are probably markers of more minimally invasive surgery in the
navigated cohort. The current study could not identify other differences in
operative time, wound infection, or return to the operating room/readmission
between navigated and conventional single level posterior instrumented lumbar
cases. LEVEL OF EVIDENCE: 3.
PMID- 28700451
TI - Do Physical Activities Trigger Flare-ups During an Acute Low Back Pain Episode?:
A Longitudinal Case-Crossover Feasibility Study.
AB - STUDY DESIGN: Prospective, longitudinal case-crossover study. OBJECTIVE: The aim
of this study was to determine whether physical activities trigger flare-ups of
pain during the course of acute low back pain (LBP). SUMMARY OF BACKGROUND DATA:
.: There exist no evidence-based estimates for the transient risk of pain flare
ups associated with specific physical activities, during acute LBP. METHODS:
Participants with LBP of duration <3 months completed frequent, Internet-based
serial assessments at both 3- and 7-day intervals for 6 weeks. At each
assessment, participants reported whether they had engaged in specific physical
activity exposures, or experienced stress or depression, during the past 24
hours. Participants also reported whether they were currently experiencing a LBP
flare-up, defined as "a period of increased pain lasting at least 2 hours, when
your pain intensity is distinctly worse than it has been recently." Odds ratios
(ORs) and 95% confidence intervals (CIs) were calculated for associations between
potential triggers during the past 24 hours, and the risk of LBP flare-ups, using
conditional logistic regression. RESULTS: Of 48 participants followed
longitudinally, 30 participants had both case ("flare") and control periods and
contributed data to the case-crossover analysis. There were 81 flare periods and
247 control periods, an average of 11 periods per participant. Prolonged sitting
(>6 hours) was the only activity that was significantly associated with flare
ups(OR 4.4, 95% CI 2.0-9.7; P < 0.001). Having either stress or depression was
also significantly associated with greater risk of flare-ups (OR 2.5, 95% CI 1.0
6.0; P = 0.04). In multivariable analyses, prolonged sitting (OR 4.2, 95% CI 1.9
9.1; P < 0.001), physical therapy (PT) (OR 0.4, 95% CI 0.1-1.0; P = 0.05), and
stress/depression (OR 2.8, 95% CI 1.2-6.7; P = 0.02) were independently and
significantly associated with LBP flare-up risk. CONCLUSION: Among participants
with acute LBP, prolonged sitting (>6 hours) and stress or depression triggered
LBP flare-ups. PT was a deterrent of flare-ups. LEVEL OF EVIDENCE: 2.
PMID- 28700452
TI - Surgical Treatment of Cervical Radiculopathy: Meta-analysis of Randomized
Controlled Trials.
AB - STUDY DESIGN: Meta-analysis of published randomized controlled trials (RCTs).
OBJECTIVE: To determine whether anterior cervical discectomy and fusion (ACDF),
cervical disc replacement (CDR), or minimally invasive posterior cervical
foraminotomy (MI-PCF) provides the best outcomes for patients with symptomatic
single-level, single-side, and cervical radiculopathy. SUMMARY OF BACKGROUND
DATA: The surgical treatment of cervical radiculopathy is still controversial.
ACDF has been widely used as a "gold standard." CDR has evolved and become a
motion-preserving alternative with a potentially lower incidence of adjacent
segment disease. However, both techniques require anterior neck dissection that
carries a potential for serious morbidity. MI-PCF is a motion-preserving
technique that can be performed with minimal invasiveness but has not gained
universal acceptance. METHODS: Electronic database search for RCTs comparing the
efficacy and effectiveness of ACDF, CDR, and MI-PCF was performed. Meta-analysis
was done for secondary surgical procedures and adverse events. RESULTS: A total
of 358 studies were retrieved, of which four RCT reports met the inclusion
criteria for this study. Three studies present clinical data comparing ACDF and
CDR, and one study presents data comparing ACDF and MI-PCF. Available data from
the RCTs analyzed concluded that ACDF, CDR, and MI-PCF result in significant
improvements in relevant symptoms, clinical, and functional outcomes in patients
with single-level, single side cervical radiculopathy refractory to nonoperative
treatment. CDR had the lowest percentage of secondary surgical procedures (P =
0.0178) whereas MICPF had the lowest percentage of adverse events (P < 0.0001).
CONCLUSION: All three techniques are effective in treating cervical radicular
symptoms. MI-PCF has the lowest rate of adverse events whereas CDR has the lowest
rate of secondary procedures. There is insufficient evidence to show which
technique is the most effective and provides the longest-lasting symptom relief.
LEVEL OF EVIDENCE: 1.
PMID- 28700454
TI - Posterior-only Hemivertebra Resection for Congenital Cervicothoracic Scoliosis:
Correcting Neck Tilt and Balancing the Shoulders.
AB - STUDY DESIGN: A retrospective study. OBJECTIVE: To evaluate radiographic and
cosmetic outcomes after posterior-only cervicothoracic hemivertebra resection and
instrumentation. SUMMARY OF BACKGROUND DATA: Cervicothoracic hemivertebra is a
rare congenital deformity. It locates between the mobile cervical spine and the
fixed thoracic spine, leading to rapid curve progression, shoulder imbalance,
fixed torticollis, and facial asymmetry. METHODS: This study reviewed a
consecutive series of 18 patients with cervicothoracic hemivertebra. All received
posterior-only hemivertebra resection and instrumentation and had a minimum
follow up of 2 years. Assessments on radiographic and cosmetic outcomes were
based on changes in measurements of scoliosis, shoulder balance, neck tilt, head
shift, and sagittal profiles. RESULTS: There were 24 hemivertebrae, consisting of
16 fully segmented and 8 semisegmented. Mean age at surgery was 9.5 +/- 3.1
years, and mean follow up was 32 +/- 10 months. Mean fusion segments were 4.8 +/-
0.6 segments. Operation time averaged 208 +/- 33 minutes, with an average blood
loss of 384 +/- 40 mL. Local scoliosis was corrected from 39 +/- 5 degrees to 16
+/- 4 degrees (P < 0.001). The distal curve had a spontaneous correction of 41
+/- 18%. With regards to shoulder balance, both T1 tilt and clavicle angle were
significantly improved, with a correction rate of 55 +/- 22% and 47 +/- 32%,
respectively. Accordingly, neck tilt was improved from 20 +/- 7 degrees to 11 +/
7 degrees , and head shift from 22 +/- 9 mm to 13 +/- 8 mm. A remarkable pedicle
screw malpositioning rate (20%) was observed, but no neurovascular injuries. One
case developed with Horner syndrome, and another one had transient radicular pain
on the right arm after surgery. CONCLUSION: For patients with congenital
cervicothoracic scoliosis, posterior-only hemivertebra resection with
instrumentation allows for excellent scoliosis correction and cosmetic
improvement. Great care should be taken to reduce the rate of pedicle screw
malpositioning. LEVEL OF EVIDENCE: 4.
PMID- 28700455
TI - Perioperative Ketamine for Analgesia in Spine Surgery: A Meta-analysis of
Randomized Controlled Trials.
AB - STUDY DESIGN: A meta-analysis of randomized controlled trials (RCTs). OBJECTIVE:
The aim of this study was to evaluate the effectiveness of perioperative
supplemental ketamine to reduce postoperative opioid analgesic consumption
following spine surgery. SUMMARY OF BACKGROUND DATA: Although low-dose
supplemental ketamine has been known to reduce pain after surgery, there is
conflicting evidence regarding whether ketamine can be effective to reduce opioid
consumption following spine surgery. METHODS: Comprehensive search of PubMed, the
Cochrane Central Register of Controlled Trials for prospective RCTs, Web of
Science, and Scopus. Patients who received supplemental ketamine were compared
with the control group in terms of postoperative morphine equivalent consumption,
pain scores, and adverse events. Mean differences (MDs) and 95% confidence
intervals (CIs) were used to describe continuous outcomes. Odds ratios (ORs) and
95% CIs were applied to dichotomous outcomes. RESULTS: A total of 14 RCTs
comprising 649 patients were selected for inclusion into the meta-analysis.
Patients who were administered adjunctive ketamine exhibited less cumulative
morphine equivalent consumption at 4, 8, 12, and 24 hours following spine surgery
(all Ps < 0.05). The ketamine group also reported lower postoperative pain scores
at 6, 12, and 24 hours (all Ps < 0.05). None of the adverse events studied
attained statistical significance (all Ps > 0.05). CONCLUSION: Supplemental
perioperative ketamine reduces postoperative opioid consumption up to 24 hours
following spine surgery. LEVEL OF EVIDENCE: 1.
PMID- 28700456
TI - Obesity and pelvic organ prolapse.
AB - PURPOSE OF REVIEW: The purpose of this review is to review the data on the
relationship of obesity and pelvic organ prolapse (POP). This review is timely
and relevant as the prevalence of obesity is increasing worldwide, and it is an
important risk factor to consider in counseling women on management of prolapse
symptoms and outcomes for surgical treatment. RECENT FINDINGS: The main findings
in the literature include: Obesity is increasing worldwide and impacts health,
social life, work and healthcare costs. Elevated BMI is an important lifestyle
factor affecting pelvic prolapse. The most probable mechanism of POP development
among obese women is the increase in intra-abdominal pressure that causes
weakening of pelvic floor muscles and fascia. Obesity is associated with
significant pelvic floor symptoms and impairment of quality of life (QOL). Weight
loss is likely not associated with anatomic improvement, but may be associated
with prolapse symptom improvement. Weight loss should be considered a primary
option in obese women for its beneficial effects on multiple organ systems and
reducing pelvic floor disorder (PFD) symptoms. Although the operation time in
obese women is significantly longer than in healthy weight women, the
complication rate of surgery has not been shown to be increased compared to
nonobese patients, regardless of route of surgery. There are data to support the
vaginal approach in obese women. Some studies have shown that women with high
body weight are associated with an increase in the risk for both anatomical and
functional recurrence, and other studies have shown no difference. SUMMARY:
Obesity is a prevalent modifiable condition that impacts PFDs including pelvic
prolapse. Patients should be counseled using clinical judgment, knowledge of the
literature and with the goal of improving QOL.
PMID- 28700457
TI - Discontinuity of Medicaid Coverage: Impact on Cost and Utilization Among Adult
Medicaid Beneficiaries With Major Depression.
AB - BACKGROUND: Gaps in Medicaid coverage may disrupt access to and continuity of
care. This can be detrimental for beneficiaries with chronic conditions, such as
major depression, for whom disruptions in access to outpatient care may lead to
increased use of acute care. However, little is known about how Medicaid coverage
discontinuities impact acute care utilization among adults with depression.
OBJECTIVE: Examine the relationship between Medicaid discontinuities and service
utilization among adults with major depression. SUBJECTS: A total of 139,164
adults (18-64) with major depression was identified using the 2003-2004 Medicaid
Analytic eXtract Files. METHODS: We used generalized linear and two-part models
to examine the effect of Medicaid discontinuity on service utilization. To
establish causality in this relationship, we used instrumental variables
analysis, relying on exogenous variation in a state-level policy for
identification. OUTCOME MEASURES: Emergency department (ED) visits, inpatient
episodes, inpatient days, and Medicaid-reimbursed costs. RESULTS: Approximately
29.4% of beneficiaries experienced coverage disruptions. In instrumental
variables models, those with coverage disruptions incurred an increase of $650 in
acute care costs per-person per Medicaid-covered month compared with those with
continuous coverage, evidenced by an increase in ED use (0.1 more ED visits per
person-month) and inpatient days (0.6 more days per-person-month). The increase
in acute costs contributed to an overall increase in all-cause costs by $310 per
person-month (all P-values<0.001). CONCLUSIONS: Among depressed adults, those
experiencing coverage disruptions have, on average, significantly greater use of
costly ED/inpatient services than those with continuous coverage. Maintenance of
continuous Medicaid coverage may help prevent acute episodes requiring high-cost
interventions.
PMID- 28700458
TI - Perceived Stress, Depressive Symptoms, and Oxidative DNA Damage.
AB - OBJECTIVE: Psychosocial stress may influence the risk of disease through its
association with oxidative DNA damage. We examined whether perceived stress and
depressive symptoms were associated with urinary excretion of 8
hydroxydeoxyguanosine (8-OHdG), with mutual interaction on 8-OHdG. METHODS: This
cross-sectional study included 6517 individuals aged 45 to 74 years who
participated, between 2010 and 2012, in a follow-up survey of an ongoing cohort
study. Perceived stress during the past year was measured using a self-report
questionnaire. Depressive symptoms were evaluated using the Zung Self-Rating
Depression Scale. Urinary 8-OHdG concentrations were measured using a column
switching high-pressure liquid chromatography system coupled to an
electrochemical detector. RESULTS: Higher perceived stress was significantly
associated with higher 8-OHdG (2.1% increase per one-category increase of stress;
ptrend = .025), even after adjusting for sex, age, supplement use, psychosocial
factors, psychotropic medication use, smoking, and body mass index. This
association was modestly attenuated after further adjustment for physical
activity, suggesting possible mediation or confounding by this factor. Depressive
symptoms were not significantly associated with 8-OHdG. No significant
interaction was detected between perceived stress and depressive symptoms on 8
OHdG. CONCLUSIONS: In a general Japanese population, we found a weak positive
association between perceived stress and urinary excretion of 8-OHdG, whereas no
association was observed between depressive symptoms and 8-OHdG. Further studies
are needed to examine whether the association between perceived stress and 8-OHdG
is modified by depressive symptoms.
PMID- 28700460
TI - A Novel Pediatric Residency Coaching Program: Outcomes After One Year.
AB - PROBLEM: The ACGME requires all residency programs to assess residents on
specialty-specific milestones. Optimal assessment of competence is through direct
observation of performance in clinical settings, which is challenging to
implement. APPROACH: The authors developed the Stanford Pediatric Residency
Coaching Program to improve residents' clinical skill development, reflective
practice, feedback, and goal setting, and to improve learner assessment. All
residents are assigned a dedicated faculty coach who coaches them throughout
their training in various settings in an iterative process. Each coaching session
consists of four parts: (1) direct observation, (2) facilitated reflection, (3)
feedback from the coach, and (4) goal setting. Coaches document each session and
participate in the Clinical Competency Committee. Initial program evaluation
(2013 -2014) focused on the program's effect on feedback, reflection, and goal
setting. Pre- and postintervention surveys of residents and faculty assessed the
quantity and quality of feedback provided to residents and faculty members'
confidence in giving feedback. OUTCOMES: Review of documented coaching sessions
showed that all 82 residents had 3 or more direct observations (range: 3-12).
Residents and faculty assessed coaches as providing higher-quality feedback and
incorporating more reflection and goal setting than noncoaches. Coaches, compared
with noncoaches, demonstrated increased confidence in giving feedback on clinical
reasoning, communication skills, and goal setting. Noncoach faculty reported
giving equal or more feedback after the coaching program than before. NEXT STEPS:
Further evaluation is under way to explore how coaching residents can affect
patient-level outcomes, and to better understand the benefits and challenges of
coaching residents.
PMID- 28700459
TI - The Microbiome in Posttraumatic Stress Disorder and Trauma-Exposed Controls: An
Exploratory Study.
AB - OBJECTIVE: Inadequate immunoregulation and elevated inflammation may be risk
factors for posttraumatic stress disorder (PTSD), and microbial inputs are
important determinants of immunoregulation; however, the association between the
gut microbiota and PTSD is unknown. This study investigated the gut microbiome in
a South African sample of PTSD-affected individuals and trauma-exposed (TE)
controls to identify potential differences in microbial diversity or microbial
community structure. METHODS: The Clinician-Administered PTSD Scale for DSM-5 was
used to diagnose PTSD according to Diagnostic and Statistical Manual of Mental
Disorders, Fifth Edition criteria. Microbial DNA was extracted from stool samples
obtained from 18 individuals with PTSD and 12 TE control participants. Bacterial
16S ribosomal RNA gene V3/V4 amplicons were generated and sequenced. Microbial
community structure, alpha-diversity, and beta-diversity were analyzed; random
forest analysis was used to identify associations between bacterial taxa and
PTSD. RESULTS: There were no differences between PTSD and TE control groups in
alpha- or beta-diversity measures (e.g., alpha-diversity: Shannon index, t =
0.386, p = .70; beta-diversity, on the basis of analysis of similarities: Bray
Curtis test statistic = -0.033, p = .70); however, random forest analysis
highlighted three phyla as important to distinguish PTSD status: Actinobacteria,
Lentisphaerae, and Verrucomicrobia. Decreased total abundance of these taxa was
associated with higher Clinician-Administered PTSD Scale scores (r = -0.387, p =
.035). CONCLUSIONS: In this exploratory study, measures of overall microbial
diversity were similar among individuals with PTSD and TE controls; however,
decreased total abundance of Actinobacteria, Lentisphaerae, and Verrucomicrobia
was associated with PTSD status.
PMID- 28700461
TI - Student Hotspotting: Teaching the Interprofessional Care of Complex Patients.
AB - PROBLEM: Individuals with complex health and social needs drive much of the total
cost of care. Addressing these individuals' needs and decreasing costs requires
interprofessional teams, called "hotspotters," who engage with communities with
high utilization. Training health professions students to succeed in the
hotspotting approach may benefit trainees, academic health centers (AHCs), and
communities. APPROACH: The Camden Coalition of Healthcare Providers and the
Association of American Medical Colleges launched the Interprofessional Student
Hotspotting Learning Collaborative in 2014. The goal was to train health
professions students working in interprofessional teams at U.S. AHCs to meet the
needs of complex patients, providing home visits and intensive case management
for up to five patients over six months. The authors report themes from 20
reflections from the five-student Virginia Commonwealth University (VCU) team.
OUTCOMES: Across 10 sites, 57 students participated during June-December 2014.
The review of the VCU experience demonstrated that the hotspotting program was
successful in teaching students how social determinants affect health and the
benefits of interprofessional teamwork for addressing the unmet health and social
needs of complex patients. Key elements that students identified for improvement
were more program structure; protected time for program activities; and
formalized processes for recruiting, retaining, and transitioning patients. NEXT
STEPS: Future iterations of the program should strengthen the curriculum on
caring for complex patients, provide protected time or academic credit, and
formally integrate teams with primary care. A larger study evaluating the
program's impact on patients, health systems, and communities should be
undertaken.
PMID- 28700462
TI - Validity of Level of Supervision Scales for Assessing Pediatric Fellows on the
Common Pediatric Subspecialty Entrustable Professional Activities.
AB - PURPOSE: Entrustable professional activities (EPAs) represent the routine and
essential activities that physicians perform in practice. Although some level of
supervision scales have been proposed, they have not been validated. In this
study, the investigators created level of supervision scales for EPAs common to
the pediatric subspecialties and then examined their validity in a study
conducted by the Subspecialty Pediatrics Investigator Network (SPIN). METHOD:
SPIN Steering Committee members used a modified Delphi process to develop unique
scales for six of the seven common EPAs. The investigators sought validity
evidence in a multisubspecialty study in which pediatric fellowship program
directors and Clinical Competency Committees used the scales to evaluate fellows
in fall 2014 and spring 2015. RESULTS: Separate scales for the six EPAs, each
with five levels of progressive entrustment, were created. In both fall and
spring, more than 300 fellows in each year of training from over 200 programs
were assessed. In both periods and for each EPA, there was a progressive increase
in entrustment levels, with second-year fellows rated higher than first-year
fellows (P < .001) and third-year fellows rated higher than second-year fellows
(P < .001). For each EPA, spring ratings were higher (P < .001) than those in the
fall. Interrater reliability was high (Janson and Olsson's iota = 0.73).
CONCLUSIONS: The supervision scales developed for these six common pediatric
subspecialty EPAs demonstrated strong validity evidence for use in EPA-based
assessment of pediatric fellows. They may also inform the development of scales
in other specialties.
PMID- 28700463
TI - Impact of obesity on the short-term outcomes of single-port laparoscopic
colectomy for colorectal cancer in the Asian population: A retrospective cohort
study.
AB - Single-port laparoscopic surgery (SPLS) is being increasingly performed for
treating colorectal cancer. Here, we aimed to assess the safety and feasibility
of SPLS for colorectal cancer in obese patients through a comparison of their
short-term outcomes with those of nonobese patients.A total of 323 patients who
underwent SPLS for colorectal cancer at our center between March 2009 and August
2014 were enrolled. The outcomes were analyzed according to the body mass index
(BMI) category: nonobese (BMI < 25), obese I (BMI: 25.0-29.9), and obese II (BMI
>= 30).Of the 323 patients, 233 (72.1%), 80 (24.8%), and 10 (3.1%), were assigned
to the nonobese, obese I, and obese II groups, respectively. The
clinicopathologic patient characteristics, such as age, gender, tumor location,
and previous laparotomy, were similar among the 3 groups. The mean operative time
(nonobese vs obese I vs and obese II groups: 269.2 vs 270.4 vs 342.8 minutes,
respectively) and estimated surgical blood loss (277.7 vs 260.5 vs 387.0 mL,
respectively) were greater in the obese II group than in the nonobese and obese I
groups, although the difference was not significant (P = .247 and P = .205,
respectively). However, the time to passage of flatus significantly differed
among the groups (P = .040); in particular, this value was significantly longer
in the obese II group than in the obese I group (P = .031). None of the other
parameters, including conversion to open or conventional laparoscopic surgery and
intra- and postoperative morbidity, significantly differed among the 3
groups.SPLS for colorectal cancer can be safely performed in obese Asian patients
with equivalent short-term outcomes as compared with that in nonobese patients.
Hence, SPLS can be safely recommended for colorectal cancer in obese patients if
the surgeon is experienced. Nevertheless, the technique used warrants further
investigation, and a large-scale prospective study is required.
PMID- 28700464
TI - Cryptococcal meningitis after transnasal transsphenoidal pituitary microsurgery
of ACTH-secreting pituitary adenoma: A case report.
AB - RATIONALE: Microbial infection should be regarded in the differential diagnosis
of neurosurgical complications after transnasal transsphenoidal pituitary
microsurgery, albeit cryptococcal meningitis is rare. This article will discuss
the risk factors of cryptococcal meningitis in patients underwent transnasal
transsphenoidal pituitary microsurgery, and summary the potential origins of
infection. PATIENT CONCERNS AND DIAGNOSIS: Here, we report a case of 37-year-old
male who had cryptococcal meningitis after transnasal transsphenoidal pituitary
microsurgery of a relapsing ACTH-secreting pituitary adenoma. INTERVENTION:
Standard therapy for Cryptococcus neoformans (fluconazole [400 mg per day] and
flucytosine) was administered and followed by maintenance dose. OUTCOMES: The
patient had been on treatment for one and a half years during follow-up and
reported neurologically well with repeated negative cerebrospinal fluid (CSF)
culture until sudden death of heart arrest. MAIN LESSONS TO LEARN: C neoformans
can be a possible cause of meningitis in immunocompetent patients after
transnasal transsphenoidal pituitary microsurgery. Risk factors, such as pre
existed pulmonary infection and Cushing-associated hypercortisolemia, should be
stressed. Promising preventive measures may include preoperative routine sputum
smear and India-ink stain for screening, preoperative treatment of cryptococcal
pneumonia, postoperative antibiotic management, and a more secure skull base
reconstruction. Radiation and pharmaceutical treatment may be alternative for
recurrent Cushing disease.
PMID- 28700465
TI - Alemtuzumab versus antithymocyte globulin induction therapies in kidney
transplantation patients: A systematic review and meta-analysis of randomized
controlled trials.
AB - Alemtuzumab (ALEM) is widely used as an induction therapy for organ
transplantation, and numerous randomized controlled trials (RCTs) have been
published to evaluate its efficacy and safety in kidney transplantation as
compared with antithymocyte globulin (ATG). The purpose of this study was to
compare the benefits and safety of ALEM with those of ATG for induction therapy.A
systematic literature search in three electronic databases, including PubMed,
EmBase, and Cochrane Library, since inception through October 2016, was conducted
to identify potential RCTs for inclusion. Trials that investigated the risk of
biopsy-proven acute rejection (BPAR), mortality, graft failure, delayed graft
function (DGF), chronic allograft nephropathy (CAN), infections, cytomegalovirus
(CMV) infections, new-onset diabetes mellitus after transplant (NODAT), and
granulocyte colony stimulation factor (GCSF) use in kidney transplant recipients
who received ALEM or ATG as an induction therapy were included. Relative risk
(RR) and 95% confidence intervals (CIs) were calculated using a random-effects
model.Six RCTs involving 446 kidney transplantation patients were included in
this meta-analysis. The effects of ALEM therapy were not significantly different
from those of ATG therapy, including the incidence of BPAR (RR: 0.77; 95% CI:
0.51-1.18; P = .229), mortality (RR: 0.64; 95% CI: 0.30-1.39; P = .263), graft
failure (RR: 0.81; 95% CI: 0.49-1.33; P = .411), DGF (RR: 1.00; 95% CI: 0.60
1.67; P = .999), CAN (RR: 1.42; 95% CI: 0.44-4.57; P = .556), infections (RR:
1.00; 95% CI: 0.74-1.35; P = .989), CMV infections (RR: 0.70; 95% CI: 0.38-1.30;
P = .263), NODAT (RR: 0.50; 95% CI: 0.18-1.36; P = .174), and GCSF use (RR: 1.16;
95% CI: 0.81-1.66; P = .413). Sensitivity analyses were consistent with the
overall analysis for all effects except CAN, suggesting that the risk of CAN
might be higher with ALEM therapy than ATG therapy (RR: 2.45; 95% CI: 1.02-5.94;
P = .046).The findings of this study suggest that the beneficial effects of ALEM
therapy are greater than those of ATG therapy in kidney transplantation patients;
however, the effects were not statistically significant because of the limited
number of trials. Further large-scale RCTs are needed to verify the treatment
effects of ALEM.
PMID- 28700466
TI - Role of breast magnetic resonance imaging in predicting malignant invasion of the
nipple-areolar complex: Potential predictors and reliability between inter
observers.
AB - In this study, we assessed the diagnostic accuracy of breast magnetic resonance
imaging (MRI) for evaluation of malignant invasion of the nipple-areolar complex
(NAC).Patients with primary operable breast cancer who underwent preoperative
breast MRI and received surgery during January 2011 to December 2013 were
collected. The accuracy and potential factors of MRI in predicting nipple
invasion were evaluated by comparing preoperative MRI with postoperative
histopathologic findings. The consistency of interobservers' variances across
different radiologists was also compared.Totally, 704 patients were enrolled in
this study, and 56 (8%) patients have pathologic NAC invasion. Several MRI
factors were potential predictors of nipple invasion. Only unilateral nipple
enhancement on MRI was the most significant independent predictor of NAC
involvement in multivariate analysis. The statistical measures, such as
sensitivity, specificity, positive predictive value (PPV), negative predictive
value (NPV), and the accuracy of breast MRI were 71.4%, 81.6%, 25.2%, 97.1%, and
80.8%, respectively, in one investigator and 78.6%, 88.1%, 36.4%, 97.9%, and
87.4%, respectively, in the other investigator.MR images showed acceptable
accuracy and impressive NPV, but low PPV in evaluation of malignant NAC invasion
preoperatively. MRI finding of unilateral nipple enhancement was the most
significant predictor of NAC involvement.
PMID- 28700467
TI - Early and midterm outcomes of thoracic endovascular aortic repair (TEVAR) for
acute and chronic complicated type B aortic dissection.
AB - Thoracic endovascular aortic repair (TEVAR) in the current era has been chosen as
a dominant and minimally invasive treatment for complicated aorta dissection.
This study aimed to assess safety and feasibility of TEVAR in acute and chronic
type B aortic dissection.Between January 2011 and December 2013, 85 patients with
complicated type B aortic dissection undergoing TEVAR were divided into acute
aortic dissection (AAD) (n = 60) group and chronic aortic dissection (CAD) group
(n = 25). Computed tomography was used to evaluate postoperative changes in
maximal aortic diameter and true and false lumen diameters at 3 levels during a
mean follow-up period of 26.4 +/- 15.6 months.The technical success rate was
100%. In-hospital and 30-day rates of death were 3.3% in acute group and 0 in
chronic group. Postdischarge rates of type I leak, type II leak, and retrograde
type A dissection were 6.7%, 5.2%, and 3.4% (acute) and 0%, 4.0%, and 4.0%
(chronic), respectively. The maximal aorta diameter remained stable in all the 3
levels in both acute and chronic group. The cumulative freedom from all-cause
mortality at 3 years was similar in acute and chronic groups (89.5% vs 95.5%, P =
.308). The cumulative freedom from aortic-related mortality was also not
significantly different in the acute and chronic groups (92.8% vs 95.2%, P =
.531). In the thoracic aorta, TEVAR treatment resulted in a significant increase
in true lumen (TL) diameter and decrease in false lumen (FL). However, in the
abdominal aorta, TEVAR did not lead to significant change in TL and FL diameters.
The rates of complete thrombosis thoracic false lumens were better than that in
the abdominal false lumen.TEVAR was a safe and effect therapy for complicated
acute and chronic type B dissection with low early and mid-term mortality and
morbidity.
PMID- 28700468
TI - Identification of SEPP1 polymorphisms is not a genetic risk factor for
preeclampsia in Chinese Han women: A clinical trial and experimental study.
AB - BACKGROUND: SEPP1 encodes selenoprotein P, which involved in oxidative stress and
plays an important role in the development of preeclampsia (PE). The aim of this
study was to investigate the association between PE and genetic variants of SEPP1
in Chinese Han women. METHODS: In all, 2434 unrelated pregnant women were
recruited, including 1034 PE cases and 1400 normal pregnant controls. TaqMan
allelic discrimination real-time PCR method was used to genotype the 2
polymorphisms of rs7579 and rs230813 in SEPP1. RESULTS: No statistically
significant difference in genotypic or allelic frequencies were found at the 2
genetic variants in SEPP1 between PE patients and controls (rs7579: genotype chi
= 2.417, P = .299 and allele chi = 0.197, P = .761, odds ratio 1.049, 95%
confidence interval 0.744-1.151; rs230813: genotype chi = 3.273, P = .195 and
allele chi = 0.252, P = .615, odds ratio 0.971, 95% confidence interval 0.864
1.091). There were also no statistically significant differences in genetic
distributions between mild/severe PE or early/late-onset PE and control
subgroups. CONCLUSION: Our data indicate that the 2 genetic variants of rs7579
and rs230813 in SEPP1 may not play a role in the pathogenesis of PE in Chinese
Han Women.
PMID- 28700469
TI - Microarray analysis of copy-number variations and gene expression profiles in
prostate cancer.
AB - BACKGROUND: This study aimed to identify potential prostate cancer (PC)-related
variations in gene expression profiles. METHODS: Microarray data from the
GSE21032 dataset that contained the whole-transcript and exon-level expression
profile (GSE21034) and Agilent 244K array-comparative genomic hybridization data
(GSE21035) were downloaded from the Gene Expression Omnibus database.
Differentially expressed genes (DEGs) and copy-number variations (CNVs) were
identified between PC and normal tissue samples. Coexpression interactions of
DEGs that contained CNVs (CNV-DEGs) were analyzed. Pathway enrichment analysis of
CNV-DEGs was performed. Drugs targeting CNV-DEGs were searched using the Drug
Gene Interaction database. RESULTS: In total, 679 DEGs were obtained, including
182 upregulated genes and 497 downregulated genes. A total of 48 amplified CNV
regions and 45 deleted regions were determined. The number of CNVs at 8q and 8p
was relatively higher in PC tissue. Only 16 DEGs, including 4 upregulated and 12
downregulated genes, showed a positive correlation with CNVs. In the coexpression
network, 3 downregulated CNV-DEGs, including FAT4 (FAT atypical cadherin 4),
PDE5A (phosphodiesterase 5A, cGMP-specific), and PCP4 (Purkinje cell protein 4),
had a higher degree, and were enriched in specific pathways such as the
calmodulin signaling pathway. Five of the 16 CNV-DEGs (e.g., PDE5A) were
identified as drug targets. CONCLUSION: The identified CNV-DEGs could be
implicated in the progression of human PC. The findings could lead to a better
understanding of PC pathogenesis.
PMID- 28700470
TI - Salivary alpha-amylase, salivary cortisol, and anxiety during a youth taekwondo
championship: An observational study.
AB - The aim of this study was to assess the stress-related responses and the coach's
capability to match perceived efforts of youth athletes during a taekwondo
championship.Using a cross-sectional study design, salivary cortisol (sC) and
alpha-amylase (sAA) were measured in 6 males and 3 females young (11.0 +/- 0.9
years) athletes at awakening, 5 minutes before, and 1 minute and 30 minutes after
official combats. State anxiety was recorded 60 minutes before the first
competition, whereas coach's and athletes' ratings of perceived exertion (RPE)
were obtained at the end of the combats. Time-matched (awakening and pre
competition) salivary samples and trait anxiety were collected 7-day
postcompetition during a resting day.No effect for match outcome emerged. No
difference emerged between athletes and coach RPEs. Higher (P = .03) state
anxiety (41.6 +/- 10.9 points) was shown than trait anxiety (34.8 +/- 7.1
points). Time-matched sAA were similar. Peak sAA observed at the end of the
combat (114.2 +/- 108.1 U/mL) was higher (P < .01) than the other samples (range:
20.6-48.1 U/mL), whereas sC increased (P < .05) from awakening (8.0 +/- 1.5
nmol/L), with peak levels observed at 30 minutes into the recovery phase (19.3 +/
4.3 nmol/L). Furthermore, pre-competition sC (16.5 +/- 4.5 nmol/L) values were
higher (P < .01) with respect to time-matched samples during the resting day (4.6
+/- 1.0 nmol/L). The 3 athletes engaged in consecutive matches showed a tendency
toward increasing sAA and sC.Taekwondo combats pose a high stress on young
athletes, eliciting a fast reactivity of the sympathetic-adreno-medullary system
relative to the hypothalamic-pituitary-adrenocortical system. Understanding the
athlete's efforts during combats, coaches are recommended to apply effective
recovery strategies between matches.
PMID- 28700471
TI - Plasma cytokines can help to identify the development of severe acute
pancreatitis on admission.
AB - Severe acute pancreatitis (AP) is associated with high morbidity and mortality.
Early severity stratification remains a challenging issue to overcome to improve
outcomes. We aim to find novel plasma cytokines for the early identification of
severe AP according to the revised Atlanta criteria.In this prospective
observational study, 30 cytokines, screened semiquantitatively with a human
multicytokine array, were submitted to quantitative determination using either
microparticle-based multiplex immunoassays analyzed on a Luminex 100 platform or
enzyme-linked immunosorbent assay kits. The cytokine profiles of patients and the
discriminative value of cytokines for severe AP were analyzed.Plasma samples of
70 patients with AP (20 mild, 30 moderately severe, and 20 severe) were selected
in this study if they were admitted within 48 hours of the onset of symptoms.
Plasma from healthy volunteers was collected as the healthy control. Growth
differentiation factor-15 (GDF-15) and pentraxin 3 (PTX3) on admission were
independent prognostic markers for the development of severe AP and had higher
discriminative powers than conventional markers (GDF-15 vs hematocrit, P = .003;
GDF-15 vs C-reactive protein, P = .037; GDF-15 vs creatinine, P = .048; GDF-15 vs
Acute Physiology and Chronic Health Evaluation II, P = .007; PTX3 vs hematocrit,
P = .006; PTX3 vs C-reactive protein, P = .047; PTX3 vs Acute Physiology and
Chronic Health Evaluation II, P = .011; PTX3 vs Bedside Index for Severity in
Acute Pancreatitis, P = .048).Plasma GDF-15 and PTX3 can help to identify the
development of severe AP on admission. Future work should validate their accuracy
in a larger, multicenter patient cohort.
PMID- 28700472
TI - A rare diaphragm in the common carotid artery: A first case report and literature
review.
AB - RATIONALE: We present a case of common carotid artery (CCA) diaphragm. To our
knowledge, this is the first reported case in the imaging literature. PATIENT
CONCERNS: A 33-year-old woman presented herself to an annual health examination
without any report of ill health. DIAGNOSES: A stenosis with aneurysm dilation on
the proximal part of the right CCA was revealed on ultrasound and CTA, by which a
diaphragm-like structure on the stenosis lesion was clearly identified. An
anatomic variant of artery was first considered. INTERVENTIONS: The patient was
followed up closely. OUTCOMES: There was no progression of her CCA stonosis 1
year later. LESSONS: This unusual and previously unreported case is presented to
alert vascular sonographers and radiologists to its existence.
PMID- 28700473
TI - Diagnostic value of plasma NGAL and intraoperative diuresis for AKI after major
gynecological surgery in patients treated within an intraoperative goal-directed
hemodynamic algorithm: A substudy of a randomized controlled trial.
AB - : Data on early markers for acute kidney injury (AKI) after noncardiovascular
surgery are still limited. This study aimed to determine the diagnostic value of
plasma neutrophil-gelatinase-associated lipocalin (pNGAL) and intraoperative
diuresis for AKI in patients undergoing major abdominal surgery treated within a
goal-directed hemodynamic algorithm.This study is a post-hoc analysis of a
randomized controlled pilot trial comparing intravenous solutions within a
hemodynamic goal-directed algorithm based on the esophageal Doppler in patients
undergoing epithelial ovarian cancer surgery. The diagnostic value of plasma NGAL
obtained at ICU admission and intraoperative diuresis was determined with respect
to patients already meeting AKI criteria 6 hours after surgery (AKI6h) and to all
patients meeting AKI criteria at least once during the postoperative course
(AKItotal). AKI was diagnosed by the definition of the Kidney Disease Improving
Global Outcome (KDIGO) group creatinine criteria and was screened up to
postoperative day 3. Receiver operating characteristic curves including a gray
zone approach were performed.A total of 48 patients were analyzed. None of the
patients had increased creatinine levels before surgery and 14 patients (29.2%)
developed AKI after surgery. Plasma NGAL was predictive for AKI6h (AUCAKI6h 0.832
(95% confidence interval [CI], 0.629-0.976), P = .001) and AKItotal (AUCAKItotal
0.710 (CI 0.511-0.878), P = .023). The gray zones of pNGAL calculated for AKI6h
and AKItotal were 210 to 245 and 207 to 274 ng mL, respectively. The lower
cutoffs of the gray zone at 207 and 210 ng mL had a negative predictive value
(NPV) (i.e., no AKI during the postoperative course) of 96.8% (CI 90-100) and
87.1% (CI 78-97), respectively. Intraoperative diuresis was also predictive for
AKI6h (AUCAKI6h 0.742 (CI 0.581-0.871), P = .019) with a gray zone of 0.5 to 2.0
mL kg h. At the lower cutoff of the gray zone at 0.5 mL kg h, corresponding to
the oliguric threshold, the NPV was 84.2% (78-92).This study indicates that pNGAL
can be used as an early marker to rule out AKI occurring within 3 days after
major abdominal surgery. Intraoperative diuresis can be used to rule out AKI
occurring up to 6 hours after surgery. TRIAL REGISTRATION: ISRCTN 53154834.
PMID- 28700474
TI - The accuracy of HIV rapid testing in integrated bio-behavioral surveys of men who
have sex with men across 5 Provinces in South Africa.
AB - We describe the accuracy of serial rapid HIV testing among men who have sex with
men (MSM) in South Africa and discuss the implications for HIV testing and
prevention.This was a cross-sectional survey conducted at five stand-alone
facilities from five provinces.Demographic, behavioral, and clinical data were
collected. Dried blood spots were obtained for HIV-related testing. Participants
were offered rapid HIV testing using 2 rapid diagnostic tests (RDTs) in series.
In the laboratory, reference HIV testing was conducted using a third-generation
enzyme immunoassay (EIA) and a fourth-generation EIA as confirmatory. Accuracy,
sensitivity, specificity, positive predictive value, negative predictive value,
false-positive, and false-negative rates were determined.Between August 2015 and
July 2016, 2503 participants were enrolled. Of these, 2343 were tested by RDT on
site with a further 2137 (91.2%) having definitive results on both RDT and EIA.
Sensitivity, specificity, positive predictive value, negative predictive value,
false-positive rates, and false-negative rates were 92.6% [95% confidence
interval (95% CI) 89.6-94.8], 99.4% (95% CI 98.9-99.7), 97.4% (95% CI 95.2-98.6),
98.3% (95% CI 97.6-98.8), 0.6% (95% CI 0.3-1.1), and 7.4% (95% CI 5.2-10.4),
respectively. False negatives were similar to true positives with respect to
virological profiles.Overall accuracy of the RDT algorithm was high, but
sensitivity was lower than expected. Post-HIV test counseling should include
discussions of possible false-negative results and the need for retesting among
HIV negatives.
PMID- 28700475
TI - Association of ventricular arrhythmia and in-hospital mortality in stroke
patients in Florida: A nonconcurrent prospective study.
AB - Stroke remains one of the leading causes of death in the United States. Current
evidence identified electrocardiographic abnormalities and cardiac arrhythmias in
50% of patients with an acute stroke. The purpose of this study was to assess
whether the presence of ventricular arrhythmia (VA) in adult patients
hospitalized in Florida with acute stroke increased the risk of in-hospital
mortality.Secondary data analysis of 215,150 patients with ischemic and
hemorrhagic stroke hospitalized in the state of Florida collected by the Florida
Agency for Healthcare Administration from 2008 to 2012. The main outcome for this
study was in-hospital mortality. The main exposure of this study was defined as
the presence of VA. VA included the ICD-9 CM codes: paroxysmal ventricular
tachycardia (427.1), ventricular fibrillation (427.41), ventricular flutter
(427.42), ventricular fibrillation and flutter (427.4), and other - includes
premature ventricular beats, contractions, or systoles (427.69). Differences in
demographic and clinical characteristics and hospital outcomes were assessed
between patients who developed versus did not develop VA during hospitalization
(chi and t tests). Binary logistic regression was used to estimate unadjusted and
adjusted odds ratios and 95% confidence intervals (CIs) between VA and in
hospital mortality.VA was associated with an increased risk of in-hospital
mortality after adjusting for all covariates (odds ratio [OR]: 1.75; 95% CI: 1.6
1.2). There was an increased in-hospital mortality in women compared to men (OR:
1.1; 95% CI: 1.1-1.14), age greater than 85 years (OR: 3.9, 95% CI: 3.5-4.3),
African Americans compared to Whites (OR: 1.1; 95% CI: 1.04-1.2), diagnosis of
congestive heart failure (OR: 2.1; 95% CI: 2.0-2.3), and atrial arrhythmias (OR:
2.1, 95% CI: 2.0-2.2). Patients with hemorrhagic stroke had increased odds of in
hospital mortality (OR: 9.0; 95% CI: 8.6-9.4) compared to ischemic
stroke.Identifying VAs in stroke patients may help in better target at risk
populations for closer cardiac monitoring during hospitalization. The impact of
implementing methods of quick assessment could potentially reduce VA associated
sudden cardiac death.
PMID- 28700476
TI - Peripheral monocytosis as a predictive factor for adverse outcome in the
emergency department: Survey based on a register study.
AB - Monocytosis is associated with chronic infections such as tuberculosis or
endocarditis as well as rheumatic and myeloproliferative disorders. Monocytes are
also involved in the pathogenesis of atherosclerosis, coronary artery disease,
and stroke. The value of monocytosis as a prognostic marker in different
diagnostic groups in the emergency setting, however, has not been investigated so
far.The aim of the article is to study monocytosis as an outcome factor in the
emergency setting.In a Swiss register study, we analyzed monocyte counts in 4238
patients aged >18 years who were admitted to the emergency department of a
regional tertiary care hospital. Monocytosis was defined as 0.8*10 cells/L.
Diagnoses were grouped into infection, cardiovascular, neurological, metabolic,
gastrointestinal, pulmonary, or other. Thirty-day mortality was defined as the
primary endpointA total of 1217 patients with monocytosis were identified.
Patients with monocytosis at admission suffered more frequently from respiratory
symptoms (17.7% vs 8.9%, P <.001) and infection as the final diagnosis (20.8% vs
10.3%, P <.001) while neurological diagnoses were significantly lower in the
monocytosis group (15.3% vs 30.9%, P <.001). Patients with monocytosis suffered
from more comorbidities such as congestive heart failure, chronic obstructive
pulmonary disease, tumor, diabetes, or renal failure but not dementia. When
adjusted for age, gender, comorbidities, and main diagnosis, the 30-day mortality
(P = .002) and length of stay (P = .001) were significantly higher in patients
with monocytosis. The 30-day mortality in patients with monocytosis was most
notably influenced by a cardiological diagnosis (odds ratio 3.91).An increased
monocyte count predicts adverse outcome in patients admitted to the emergency
department. Mechanistic studies will be necessary to specify the potentially
detrimental role of monocytosis in critical illness.
PMID- 28700477
TI - Application of the SYNTAX score in interventional cardiology: A systematic review
and meta-analysis.
AB - BACKGROUND: Should the SYNTAX score be integrated in Interventional Cardiology?
Should it really be considered as a vital decision-making tool in percutaneous
coronary intervention (PCI)? To confirm the importance of this score, we aimed to
systematically compare the postinterventional adverse cardiovascular outcomes
which were observed in patients who were allotted a low versus a high SYNTAX
score. METHODS: Randomized controlled trials and observational studies which were
published from January 2007 to January 2017 were identified from MEDLINE, EMBASE,
and the Cochrane databases using the searched terms 'SYNTAX score and
percutaneous coronary intervention.' Adverse cardiovascular outcomes were
considered as the major endpoints. Risk ratios (RRs) with 95% confidence
intervals (CIs) were used as the statistical parameters, and the main analysis
was carried out by the RevMan 5.3 software. RESULTS: Sixteen studies with a total
number of 19,751 participants (8589 participants with a low versus 11,162
participants with a high SYNTAX score) were included. Current results showed
mortality to be significantly higher with a higher SYNTAX score (RR 2.09, 95% CI
1.78-2.46, P = .00001). Cardiac death also significantly favored a low SYNTAX
score (RR 2.08, 95% CI 1.66-2.61, P = .00001. Similarly, myocardial infarction,
major adverse cardiac events, repeated revascularization, and stent thrombosis
were significantly higher following a high SYNTAX score (RR 1.71, 95% CI 1.45
2.03, P = .00001; RR 2.03, 95% CI 1.81-2.26, P = .00001; RR 1.96, 95% CI 1.69
2.28, P = .00001; and RR 3.16, 95% CI 2.17-4.59, P = .00001, respectively). Even
when patients with ST-segment elevation myocardial infarction were separately
analyzed, a low SYNTAX score was still significantly associated with lower
adverse outcomes. CONCLUSIONS: This analysis is a confirmatory piece of evidence
to show that the application of the SYNTAX score in Interventional Cardiology is
apparently relevant. The use of this scoring system to grade patients with
coronary artery disease and to further guide for revascularization should be
encouraged.
PMID- 28700478
TI - Impact of nonsteroidal aromatase inhibitors on steroid profile in a Chinese
population.
AB - Steroid profiling was introduced to determine the endogenous steroid misuse in
sports. Thus, screening for the exogenous use of these prohibited substances can
be established by monitoring a range of endogenous steroids, which constitute the
steroid profile and evaluate their concentrations and ratios against reference
values. The steroid profiling is currently based on population statistics. As
large interindividual variations exist, athlete biological passport (ABP)
analysis is ongoing. This study aimed to identify new biomarker(s) for aromatase
inhibitor detection in sports using statistical analysis and adapt the model into
ABP analysis.Forty-one Chinese nonathlete volunteers (21 males and 20 females)
were administered 3 nonsteroidal aromatase inhibitors (aminoglutethimide,
letrozole, and anastrozole) independently. Statistical analysis was performed on
16 steroid profile parameters.After administration, the concentrations of
endogenous androgen biomarkers including testosterone (T), epitestosterone,
androsterone (AN), etiocholanolone (ETIO), 5alpha-diol, 5beta-diol, and
dehydroepiandrosterone were increased, while the level of estrogen was decreased.
These biomarkers returned to the baselines levels within 1 month. In females, the
concentrations of endogenous biomarkers were affected by nonsteroidal aromatase
inhibitors, without a common trend. Three new endogenous biomarkers (AN/estrone,
ETIO/estrone, and T/estrone) elevated significantly after treatment. The 3 new
models were more sensitive than the World Anti-Doping Agency ratio biomarkers.
They were also effective in exponentially weighted moving average chart
analysis.Verification experiment demonstrated that the biomarker T/estrone was
valid in judging the steroidal aromatase inhibitor abuse. The screening of these
new endogenous biomarkers can provide additional parameters to support ABP
monitoring and specific information regarding the administered steroids.
PMID- 28700479
TI - The investigation of CD4+T-cell functions in primary HIV infection with
antiretroviral therapy.
AB - Human immunodeficiency virus (HIV) infection leads to reduced CD4T-cell counts
and immune dysfunction. Initiation of antiretroviral therapy (ART) in HIV primary
infection has been recommended to achieve an optimal clinical outcome, but a
comprehensive study on restoration of CD4T-cell function in primary HIV-infected
individuals with ART still needs to be eluciated. We investigated longitudinal
changes in the CD4T-cell counts, phenotypes, and functions in HIV-infected
individuals with early ART (initiated within 6 months after HIV infection) or
later ART (initiated more than 12 months after HIV infection). Patients from
early ART and later ART groups had received ART for at least 1 year. Individuals
with early ART had more CD4T cells, a faster rate of CD4T-cell recovery than
those receiving later ART; the levels of CD4T-cell activation and senescence were
lower in early ART compared to those with later ART (P = .031; P = .016), but the
activation was higher than normal controls (NC) (P = .001); thymic emigrant
function was more upregulated in early ART than in later ART (P = .015), but
still lower than NC (P = .027); proliferative capacity and interferon-gamma
secretion of CD4T cells were significantly decreased in primary infection (P <
.001; P = .029), and early ART restored these CD4T-cell functions, there is no
difference with NC, later ART could partially restore the functions of CD4T
cells, but it remained lower than that of NC (P = .005; P = .019). Early ART
could better improve CD4T-cell function.
PMID- 28700480
TI - Prognostic significance of serum procalcitonin in patients with unresectable
hepatocellular carcinoma treated with transcatheter arterial chemoembolization: A
retrospective analysis of 509 cases.
AB - Although procalcitonin (PCT) is a valid marker for early diagnosis of bacterial
infections, its accuracy in hepatocellular carcinoma (HCC) patients is unknown.
The aim of this study was to investigate the prognostic significance of PCT in
patients with unresectable HCC treated with transcatheter arterial
chemoembolization (TACE).A total of 509 patients with unresectable HCC initially
treated with TACE were enrolled in this retrospective study. According to
quartile of the PCT values, all patients were divided into 4 groups. Overall
survival (OS) was evaluated with the Kaplan-Meier method. Significant difference
was estimated with the Log rank method. Univariate and multivariate analyses were
used for evaluating the significance of the prognostic factor.The median follow
up period was 18 months and there were significant differences in the survival
rates between the 4 groups. The HR (95% CI) for all-cause mortality comparing
patients with PCT Quartile2-4 to patient with Quartile1 (HR = 1.00) were 1.353
(1.023-1.791), 1.799 (1.354-2.390), 1.960 (1.455-2.639), respectively, (P <
.001). PCT level was an important prognostic factor for predicting the prognosis
of patients with unresectable HCC treated with TACE.
PMID- 28700481
TI - A multiparameter model predicting in-hospital mortality in malignant cerebral
infarction.
AB - The early identification of patients with large hemisphere infarctions (LHIs) at
risk of fatal brain edema may result in better outcomes. A quantitative model
using parameters obtained at admission may be a predictor of in-hospital
mortality from LHI.This prospective study enrolled all patients with LHI
involving >50% of the middle cerebral artery (MCA) admitted to our neurological
intensive care unit within 48 hours of symptom onset. Early clinical and
radiographic parameters and the baseline CHADS2 score (congestive heart failure,
hypertension, age >= 75 years, diabetes mellitus, stroke [double weight]) were
analyzed regarding their ability to predict patient outcomes.Seventy-seven
patients with LHIs were identified, 33 (42.9%) with complete MCA infarction
(CMCA), and 44 (57.1%) with incomplete MCA infarction (IMCA). The predictors of
CMCA score included: >1/3 early hypodensity in computed tomography findings,
hyperdense MCA sign, brain edema, initial National Institutes of Health Stroke
Scale (NIHSS) score >=17, and stroke in progression during the 1st 5 days of
admission. The cutoff CMCA score was 2, with a sensitivity of 81.8% and
specificity of 70.5%. Mortality score 1, used for predicting in-hospital
mortality from LHI, included CMCA and CHADS2 scores >=4 (sensitivity 100.0%,
specificity 57.4%), and mortality score 2 included CMCA and CHADS2 scores >=4,
and NIHSS score >=26, during the 1st 5 days (sensitivity 100.0%, specificity
91.7%).Patients qualifying for a mortality score of 2 were at high-risk of in
hospital mortality from LHI. These findings may aid in identifying patients who
may benefit from invasive therapeutic strategies, and in better describing the
characteristics of those at risk of mortality.
PMID- 28700482
TI - Beneficial effects of Fu-Zheng-Qu-Zhuo oral liquid combined with standard
integrated therapy in patients with chronic kidney disease (stage 3-4): A
randomized placebo-controlled clinical trial.
AB - BACKGROUND: The high worldwide prevalence of chronic kidney disease (CKD) is a
critical health problem and the development of more effective therapies is
urgently needed. We conducted a randomized, double-blinded, placebo-controlled
clinical trial from October 2010 to December 2012 to assess whether Fu-Zheng-Qu
Zhuo oral liquid (FZQZ) has a beneficial effect in preventing CKD progression
when added to standard integrated therapies. METHODS: Patients with CKD stage 3
to 4 from 3 hospitals in Beijing, China were enrolled. Patients were randomly
assigned to the FZQZ or placebo groups and were treated with standard integrated
therapy plus FZQZ or placebo (20 mL each time, 3 times/d) for 12 months. Patients
received post-trial follow-up until October 2014. The primary outcome was the
estimated glomerular filtration rate (eGFR)-Slope (mL/min per 1.73 m2 per month)
during the in-trial time, which was calculated by the eGFR regression curve
estimated from each serum creatinine measurement during the in-trial period.
Secondary outcomes were changes in 24-h urine protein excretion (24-h UP) and
albumin and hemoglobin levels from baseline during the in-trial period. Time to
composite endpoint events (initiation of long-term dialysis, doubling of serum
creatinine, or CKD-related death during the in-trial and post-trial phases) was
assessed as a secondary outcome. RESULTS: A total of 68 patients (43 in the FZQZ
group and 25 in the placebo group) completed the in-trial and post-trial phases,
with an average follow-up time of 31.6 +/- 9.6months. The FZQZ group had amean
eGFR-Slope of 0.25 +/- 1.44 as compared with -0.72 +/- 1.46 (mL/min per 1.73m2
per month) in the placebo group during the in-trial period (P = .003). The FZQZ
group showed decreased 24-h UP, with a change from baseline of -0.08
(interquartile range [IQR], -0.33 to 0.01) versus 0.01 (IQR, -0.19 to 0.33) g/24h
in the placebo group (P = .049). Decreased risk of composite endpoint events was
observed only in the post-trial phase (hazard ratio = 0.42, 95% confidence
interval: 0.16-1.11, P = .038). No significant differences in albumin and
hemoglobin level changes were observed. CONCLUSION: Adding FZQZ oral liquid to
standard integrated therapies may aid in attenuating CKD progression.
PMID- 28700483
TI - Endoscopic ultrasound guided fine needle aspiration versus endoscopic ultrasound
guided fine needle biopsy in sampling pancreatic masses: A meta-analysis.
AB - BACKGROUND: The comparison between endoscopic ultrasound guided fine needle
aspiration (EUS-FNA) and endoscopic ultrasound guided fine needle biopsy (EUS
FNB) for the diagnosis of pancreatic masses is still controversial. Many factors
can affect the final results. METHODS: Databases, such as PubMed, EMBASE,
Cochrane Library, and Science Citation Index updated from 2000 to 2016 were
searched to include eligible articles. In the meta-analysis, the main outcome
measurements were the diagnostic accuracy, number of needle passes, specimen
adequacy, the rate of complications, and technical success. RESULTS: Eight
randomized controlled trials (RCTs) were identified, and a total of 921 cases
were included in the meta-analysis. The diagnostic accuracy was not significantly
different between the FNA and FNB groups. The specimen adequacy was higher in the
FNB group compared with the FNA group. The number of needle passes to obtain
sufficient tissue was lower in the FNB group. The rate of adverse events and
technical success did not significantly differ between the 2 groups. But, the
forest plot showed a trend toward lower technical success rate and a trend toward
higher diagnostic accuracy in the FNB group, compared with FNA. CONCLUSION: We
provide the evidence that FNB is comparable to FNA in terms of diagnostic
accuracy, adverse events, and technical success. FNB gives higher specimen
adequacy than that of FNA, despite performance of fewer needle passes.
PMID- 28700484
TI - Cardiac metastasis of tongue squamous cell carcinoma complicated by pulmonary
embolism: A case report.
AB - RATIONALE: Cardiac metastasis is known as a rare complication of head and neck
malignancy. PATIENT CONCERNS: We present a 58-year-old woman patient with a
history of tongue carcinoma who was admitted in emergency department for sudden
chest pain. Imaging work-up by computed tomography (CT) and positron emission
tomography-computed tomography (PET-CT) diagnosed a cardiac metastasis
complicated by intraventricular thrombus and pulmonary embolism. DIAGNOSIS:
Cardiac metastasis from tongue carcinoma complicated by pulmonary embolism.
INTERVENTIONS: After undergoing 2 cycles of palliative chemotherapy, the patient
declined any further treatment. OUTCOMES: Patient died 3 months after the
diagnosis of cardiac metastasis. LESSONS: Cardiac metastasis should be considered
as a differential diagnosis in patients with a history of head and neck
malignancy who present non-specific cardiac symptoms.
PMID- 28700485
TI - Value of contrast-enhanced ultrasound in differential diagnosis of solid lesions
of pancreas (SLP): A systematic review and a meta-analysis.
AB - BACKGROUND: Contrast-enhanced ultrasound (CEUS) is considered a novel method for
diagnosing pancreatic cancer, but currently, there is no conclusive evidence of
its accuracy. Using CEUS in discriminating between pancreatic carcinoma and other
pancreatic lesions, we aimed to evaluate the diagnostic accuracy of CEUS in
predicting pancreatic tumours. METHODS: Relevant studies were selected from the
PubMed, Cochrane Library, Elsevier, CNKI, VIP, and WANFANG databases dating from
January 2006 to May 2017. The following terms were used as keywords: "pancreatic
cancer" OR "pancreatic carcinoma," "contrast-enhanced ultrasonography" OR
"contrast-enhanced ultrasound" OR "CEUS," and "diagnosis." The selection criteria
are as follows: pancreatic carcinomas diagnosed by CEUS while the main reference
standard was surgical pathology or biopsy (if it involved a clinical diagnosis,
particular criteria emphasized); SonoVue or Levovist was the contrast agent; true
positive, false positive, false negative, and true negative rates were obtained
or calculated to construct the 2 * 2 contingency table; English or Chinese
articles; at least 20 patients were enrolled in each group. The Quality
Assessment for Studies of Diagnostic Accuracy was employed to evaluate the
quality of articles. Pooled sensitivity, specificity, positive likelihood ratio,
negative likelihood ratio, diagnostic odds ratio, summary receiver-operating
characteristic curves, and the area under curve were evaluated to estimate the
overall diagnostic efficiency. Pooled sensitivity, specificity, positive
likelihood ratio, and negative likelihood ratio with 95% confidence intervals
(CIs) were calculated with fixed-effect models. RESULTS: Eight of 184 records
were eligible for a meta-analysis after independent scrutinization by 2
reviewers. The pooled sensitivity, specificity, positive likelihood ratio,
negative likelihood ratio, and diagnostic odds ratios were 0.86 (95% CI 0.81
0.90), 0.75 (95% CI 0.68-0.82), 3.56 (95% CI 2.64-4.78), 0.19 (95% CI 0.13-0.27),
and 22.260 (95% CI 8.980-55.177), respectively. The area under the SROC curve was
0.9088. CONCLUSION: CEUS has a satisfying pooled sensitivity and specificity for
discriminating pancreatic cancer from other pancreatic lesions.
PMID- 28700486
TI - Progression of primary myelofibrosis to polycythemia vera: A case report.
AB - RATIONALE: This case report describes the progression of primary myelofibrosis
(PMF) to polycythemia vera (PV), and discuss its potential mechanisms. PATIENT
CONCERNS: The patient was admitted because of abdominal discomfort and enlarged
spleen for 19 months. DIAGNOSIS: A case of PMF progressed to PV was
retrospectively analyzed. There were 19 months between the diagnosis of PMF and
PV. The JAK2 V617F mutation was positive before and after the diagnosis of PV;
however, new chromosomal abnormalities were detected during the progression.
INTERVENTIONS: For treatment of PMF, the danazol, calcitriol, and thalidomide
were given. Then, the use of thalidomide and calcitriol was stopped, and
hydroxyurea was started. For treatment of PV, interferon treatment was given,
whereas hydroxyurea was continued. OUTCOMES: After 30 months of the progression
(at the recent follow-up), this patient had no obvious symptoms or thrombosis.
LESSONS: PMF rarely progresses to PV, however, the progression will significantly
improve the quality of life and prognosis.
PMID- 28700487
TI - Prognostic role of methylated GSTP1, p16, ESR1 and PITX2 in patients with breast
cancer: A systematic meta-analysis under the guideline of PRISMA.
AB - BACKGROUND: BRCA1 and RASSF1A promoter methylation has been reported to be
correlated with a worse survival in patients with breast cancer. However, the
prognostic values of GSTP1, p16, ESR1, and PITX2 promoter methylation in breast
cancer remain to be determined. Here, we performed this study to evaluate the
prognostic significance of GSTP1, p16, ESR1, and PITX2 promoter methylation in
breast cancer. METHODS: A range of online databases was systematically searched
to identify available studies based on the Preferred Reporting Items for
Systematic reviews and Meta-Analyses (PRISMA) guideline. The pooled hazard ratios
(HRs) with their 95% confidence intervals (95% CIs) were applied to estimate the
prognostic effect of GSTP1, p16, ESR1, and PITX2 promoter methylation in breast
cancer for multivariate regression analysis. RESULTS: 13 eligible articles
involving 3915 patients with breast cancer were analyzed in this meta-analysis.
In a large patient population, GSTP1 showed a trend toward a worse prognosis in
overall survival (OS) (HR = 1.64, 95% CI = 0.93-2.87, P = .085). PITX2 promoter
methylation was significantly correlated with a worse prognosis in OS (HR = 1.57,
95% CI = 1.15-2.14, P = .004), but no association between p16 promoter
methylation and OS (HR = 0.92, 95% CI = 0.31-2.71, P = .884). PITX2 promoter
methylation was significantly correlated with an unfavorable prognosis of
patients with breast cancer in metastasis-free survival (MFS) (HR = 1.73, 95% CI
= 1.33-2.26, P < .001). The result from 3 studies with 227 cases showed that ESR1
promoter methylation was linked to a worse prognosis in OS (HR = 1.55, 95% CI =
1.06-2.28, P = .025). CONCLUSIONS: Our findings suggest ESR1 and PITX2 promoter
methylation may be correlated with a worse survival of patients with breast
cancer (ESR1: OS, PITX2: OS and MFS). The clinical utility of aberrantly
methylated ESR1 and PITX2 could be a promising factor for the prognosis of breast
cancer.
PMID- 28700488
TI - Correlation of iodine uptake and perfusion parameters between dual-energy CT
imaging and first-pass dual-input perfusion CT in lung cancer.
AB - To investigate the potential relationship between perfusion parameters from first
pass dual-input perfusion computed tomography (DI-PCT) and iodine uptake levels
estimated from dual-energy CT (DE-CT).The pre-experimental part of this study
included a dynamic DE-CT protocol in 15 patients to evaluate peak arterial
enhancement of lung cancer based on time-attenuation curves, and the scan time of
DE-CT was determined. In the prospective part of the study, 28 lung cancer
patients underwent whole-volume perfusion CT and single-source DE-CT using 320
row CT. Pulmonary flow (PF, mL/min/100 mL), aortic flow (AF, mL/min/100 mL), and
a perfusion index (PI = PF/[PF + AF]) were automatically generated by in-house
commercial software using the dual-input maximum slope method for DI-PCT. For the
dual-energy CT data, iodine uptake was estimated by the difference (lambda) and
the slope (lambdaHU). lambda was defined as the difference of CT values between
40 and 70 KeV monochromatic images in lung lesions. lambdaHU was calculated by
the following equation: lambdaHU = |lambda/(70 - 40)|. The DI-PCT and DE-CT
parameters were analyzed by Pearson/Spearman correlation analysis,
respectively.All subjects were pathologically proved as lung cancer patients
(including 16 squamous cell carcinoma, 8 adenocarcinoma, and 4 small cell lung
cancer) by surgery or CT-guided biopsy. Interobserver reproducibility in DI-PCT
(PF, AF, PI) and DE-CT (lambda, lambdaHU) were relatively good to excellent
(intraclass correlation coefficient [ICC]Inter = 0.8726-0.9255, ICCInter = 0.8179
0.8842; ICCInter = 0.8881-0.9177, ICCInter = 0.9820-0.9970, ICCInter = 0.9780
0.9971, respectively). Correlation coefficient between lambda and AF, and PF were
as follows: 0.589 (P < .01) and 0.383 (P < .05). Correlation coefficient between
lambdaHU and AF, and PF were as follows: 0.564 (P < .01) and 0.388 (P < .05).Both
the single-source DE-CT and dual-input CT perfusion analysis method can be
applied to assess blood supply of lung cancer patients. Preliminary results
demonstrated that the iodine uptake relevant parameters derived from DE-CT
significantly correlated with perfusion parameters derived from DI-PCT.
PMID- 28700489
TI - The effect of intraoperative dexmedetomidine on acute kidney injury after
pediatric congenital heart surgery: A prospective randomized trial.
AB - BACKGROUND: Dexmedetomidine has been reported to have a renal protective effect
after adult open heart surgery. The authors hypothesized that intraoperative
infusion of dexmedetomidine would attenuate the decrease in renal function after
pediatric open heart surgery. METHODS: Twenty-nine pediatric patients (1-6 years)
scheduled for atrial or ventricular septal defect repair were randomly assigned
to receive either continuous infusion of normal saline (control group, n = 14) or
dexmedetomidine (a bolus dose of 0.5 MUg/kg and then an infusion of 0.5 MUg/kg/h)
(dexmedetomidine group, n = 15) from anesthesia induction to the end of
cardiopulmonary bypass. Serum creatinine (Scr) was measured before surgery (T0),
10 minutes after anesthesia induction (T1), 5 minutes after cardiopulmonary
bypass weaning (T2), 2 hours after T2 (T3), and after postoperative day 1 (POD1)
and postoperative day 2 (POD2) and estimated glomerular filtration rates (eGFRs)
were calculated. Renal biomarkers were measured at T1, T2, and T3. Acute kidney
injury (AKI) was defined as an absolute increase in Scr of >= 0.3 mg/dL or a
percent increase in Scr of >=50%. RESULTS: The incidence of AKI during the
perioperative period was significantly higher in the control group than in the
dexmedetomidine group (64% [9/14] vs 27% [4/15], P = .042). eGFR was
significantly lower in the control group than in the dexmedetomidine group at T2
(72.6 +/- 15.1 vs 83.9 +/- 13.5, P = .044) and T3 (73.4 +/- 15.4 vs 86.7 +/-
15.9, P = .03). CONCLUSION: Intraoperative infusion of dexmedetomidine may reduce
the incidence of AKI and suppress post-bypass eGFR decline.
PMID- 28700490
TI - Side effects associated with the treatment of multidrug-resistant tuberculosis at
a tuberculosis referral hospital in South Korea: A retrospective study.
AB - Patients with drug-susceptible tuberculosis (TB) show good tolerance of the
medications used and have few side effects. However, medications used to treat
multidrug-resistant tuberculosis (MDR-TB) have many known side effects. Here, we
studied the occurrence of side effects due to treatment of patients with MDR
TB.We conducted a retrospective and consecutive review of the medical records of
256 patients who received treatment for MDR-TB between January 2006 and December
2011.One or more side effects were observed in 95 (37.1%) of the 256 patients.
These side effects led to the suspension of the use of 1 or more drugs from the
regimen of individualized treatment prescribed for 44 of the patients (17.2%).
The side effects observed most frequently included gastrointestinal disturbance
(18.4%), psychiatric disorder (5.5%), arthralgia (4.7%), hepatitis (3.9%),
peripheral neuropathy (3.1%), hypothyroidism (2.3%), epileptic seizures (2%),
dermatological effects (2%), ototoxicity (1.6%), and nephrotoxicity (1.2%). The
treatment was successful in 220 (85.9%) patients with MDR-TB.Our study may help
in formulating strategies for the timely and aggressive management of drug side
effects. This may reduce the suspension of therapy and increase the rate of
clinical success.
PMID- 28700491
TI - Long-term follow-up of patients with intestinal neuronal dysplasia type B:
Protocol for an observational, ambispective, and comparative study.
AB - Intestinal neuronal dysplasia type B (IND-B) is a pathological entity of the
group of gastrointestinal neuromuscular diseases characterized by complex
alterations in the enteric nervous system. Patients typically present with
intestinal constipation, sometimes complicated by episodes of intestinal
obstruction. The 2 therapeutic modalities include conservative clinical treatment
and surgical treatment. Nevertheless, the results of the different therapeutic
modalities are conflicting, and follow-up studies are scarce and include only a
limited number of patients.This is a single-center, ambispective, observational,
longitudinal, and comparative follow-up study to compare the results of
conservative clinical and surgical treatments in patients with IND-B. Sixty-three
patients (<15 years) who received this diagnosis will be included. These patients
will be divided into 2 groups according to the type of treatment that they
previously received: 29 patients in the surgical treatment group and 34 patients
in the conservative treatment group. Previous data will be recovered from the
medical records of the study patients, including signs and symptoms present at
the time of diagnosis, particularly those related to bowel habits, and treatments
undergone. Later, these patients will be invited to participate in a
semistructured interview during which aspects related to the long-term functional
results of the bowel habit and quality of life will be investigated after a
minimum interval of 5 years posttreatment.This project aims to assess the long
term clinical evolution of patients diagnosed with IND-B and compare the results
obtained following conservative clinical and surgical treatments.This protocol
will provide sufficient data to analyze the long-term clinical outcome obtained
through the 2 treatment modalities proposed for patients with IND-B.
PMID- 28700492
TI - An unusual association between hemophagocytic lymphohistiocytosis, mixed
connective tissue disease, and autoimmune hemolytic anemia: A case report.
AB - RATIONALE: In the adult patient, hemophagocytic lymphohistiocytosis (HLH) is
uncommon and frequently difficult to diagnose due to its nonspecific presentation
and numerous complications. PATIENT CONCERNS: Herein, we present the case of a 25
year-old female who initially presented for evaluation of persistent fevers and
fatigue. She was found to have splenomegaly, generalized lymphadenopathy,
pancytopenia, and acute hepatic failure. DIAGNOSES, INTERVENTIONS, AND OUTCOMES:
Her course was further complicated by the development of nephrotic syndrome and
autoimmune hemolytic anemia (AIHA). Antinuclear antibody and ribonucleoprotein
were positive, with concurrent physical examination findings, indicating
underlying mixed connective tissue disease (MCTD). Ferritin was greater than
40,000 ng/dL. Viral studies, including hepatitis A, B, and C, cytomegalovirus,
and Epstein-Barr virus were negative. On the basis of her clinical presentation,
a diagnosis of HLH secondary to MCTD was made. This was later confirmed on liver
biopsy. She was started on high-dose prednisone and her symptoms completely
resolved. She was then transitioned to azathioprine, hydroxychloroquine,
prophylactic antibiotics, and a prednisone taper for long-term management.
LESSONS: This case is notable for the association of both AIHA and MCTD with HLH,
providing support for a possible relationship between these 3 conditions.
PMID- 28700493
TI - Halo-pelvic traction for severe kyphotic deformity secondary to spinal
tuberculosis.
AB - To evaluate the efficacy and safety of Halo-pelvic ring traction in the treatment
of severe kyphotic deformity secondary to spinal tuberculosis.Eighty patients
with severe kyphotic deformity due to spinal tuberculosis were included in the
study. Forty of those patients (experimental group) received Halo- pelvic ring
traction before surgery and the rest (control group) received surgical treatment
directly. Two groups were compared by means of the duration of surgery,
intraoperative blood loss, correction of Cobb angle, change in patient height,
and American Spinal Injury Association (ASIA) impairment scale.Halo-pelvic
traction group achieved significantly (P < .05) better results than direct
surgical treatment group by means of the time of surgery (244 +/- 58 minutes vs
276 +/- 47 minutes, P = .036), intraoperative blood loss (950 +/- 236 mL 1150 +/-
305 mL, P = .018), correction of Cobb angle (68.3 +/- 12.6 vs 55.6 +/- 13.8, P =
.001), change in patient height (9.4 +/- 4.0 cm vs 6.8 +/- 3.8 cm, P = .024). The
mean improvement of ASIA scale was more in the experimental group than in the
control group (0.23 +/- 0.07 vs 0.15 +/- 0.06); however, the difference is not
statistically significant (P = .09).Halo-pelvic ring traction before osteotomy
can be applied in patients with severe spinal kyphotic deformity due to spinal
tuberculosis to increase efficacy and safety of surgical treatment.
PMID- 28700494
TI - A novel classification for atypical Hangman fractures and its application: A
retrospective observational study.
AB - Atypical Hangman fractures (AHF) were first formally reported and considered to
be more often associated with neurologic deficit in 1993. However, there is a
paucity of literature focusing on these fractures. The purpose of the
retrospective study was to introduce a new classification scheme for AHF and its
application.Sixty-two patients with Hangman fractures were identified. There were
46 (74.2%, 46/62) AHF patients, including 29 type I, 9 type II, 5 type IIa, and 3
type III fractures (Levine-Edwards classification). Based on fracture patterns,
incidence, and their impact on neurologic status, a primary classification for
AHF was devised. The clinical features of AHF were observed, and a new
classification was introduced. The appropriate treatment strategy of AHF was
discussed.Of 46 AHF patients, 27 underwent surgical treatment (24 with posterior
approach with screw-rod fixation and fusion, 1 with anterior approach by C2/3
discectomy and fusion, and 2 with anterior and posterior approach), and the
remaining 19 patients underwent nonoperative treatment. No patient complained
severe neck pain at final follow-up. Neurologic status improved 1 to 2 grade in
12 cases with neurologic deficit. All patients achieved bony fusion within the
follow-up period.AHF should be recognized as a distinct fracture subtype. The new
classification for AHF is based on the feature of fracture patterns, injury
mechanism, incidence, and their impact on neurologic deficit. And the new
classification is complementary to Levine-Edwards.
PMID- 28700495
TI - Immune recovery of middle-aged HIV patients following antiretroviral therapy: An
observational cohort study.
AB - In HIV-infected persons, age is negatively associated with optimal CD4 recovery
following antiretroviral therapy. Our understanding of the situation in older
adults, especially the middle-aged is, however, limited. We undertook to examine
the latter's pattern of CD4/CD8 recovery following antiretroviral
therapy.Retrospective clinical cohort data of HIV patients diagnosed between 1985
and 2014 in Hong Kong were collected. They were categorized by age at treatment
initiation, viz., young adults (age 18-49), middle-aged (age 50-64), and elderly
(>=65 years' old). Predictors of immune recovery (CD4 count, CD8 count, CD4/CD8
ratio) over time were examined using multivariable linear generalized estimating
equations.A total of 2754 patients (aged >=18) have been on antiretroviral
therapy, with baseline characteristics similar between middle-aged and the
elderly. Late diagnosis, defined as progression to AIDS within 3 months of HIV
diagnosis, was less common in middle-aged (odds ratio = 0.58, 95% confidence
interval = 0.37-0.91). Among Chinese patients who have been on treatment for >=4
years (n = 913), 80.6%, 14.6%, and 4.8% were young adults, middle-aged, and
elderly respectively. Late treatment initiation, defined as AIDS diagnosis or CD4
count <=100 cells/MUL before treatment, was common in middle-aged and elderly,
the former however had faster CD4 recovery (3.95 vs. 3.36 cells/MUL/month), but
slower CD8 decline (-1.76 vs. -4.34 cells/MUL/month) and CD4/CD8 normalization
(0.009 vs. 0.0101/month).As a transitional age group, the immune recovery of
middle-aged patients lagged behind young adults largely because of late treatment
initiation. Following adoption of early and non-CD4-guided treatment initiation,
their long-term clinical outcome is expected to improve.
PMID- 28700496
TI - Immediate effect of subliminal priming with positive reward stimuli on standing
balance in healthy individuals: A randomized controlled trial.
AB - BACKGROUND: Information received subconsciously can influence exercise
performance; however, it remains unclear whether subliminal or supraliminal
reward is more effective in improving standing balance ability when priming
stimuli are subconsciously delivered. The present study aimed to compare the
effects of subliminal priming-plus-subliminal reward stimuli (experimental) with
subliminal priming-plus-supraliminal reward stimuli (control) on standing balance
ability. METHODS: This was a single-blind (outcome assessor), parallel-group,
randomized controlled trial involving healthy young adults recruited from a
university in Japan. Assessments were conducted at baseline and immediately after
intervention. The primary outcome was the functional reach test (FRT)
measurement. The secondary outcome was one-leg standing time (OLST) with eyes
closed. Of the 52 participants screened, 25 were randomly assigned to
experimental and control groups each. RESULTS: Both interventions were effective
for improving the FRT between the baseline and intervention; however, smaller
improvements were observed in the experimental group. We found a large between
groups effect size immediately after the intervention for the FRT (d = -0.92). In
contrast, there were no differences in improvements in OLST between the 2 groups
(d = -0.06); furthermore, neither intervention was found to be effective for this
parameter. CONCLUSION: We concluded that subliminal priming with conscious reward
stimuli results in improvements in immediate-term forward reach ability, which is
superior to that achieved by subliminal priming with subconscious reward stimuli.
PMID- 28700497
TI - Functional and morphological evolution of remnant pancreas after resection for
pancreatic adenocarcinoma.
AB - Functional and morphological evolution of remnant pancreas after resection for
pancreatic adenocarcinoma is investigated.The medical records of 45 patients who
had undergone radical resection for pancreatic adenocarcinoma from March 2010 to
September 2013 were reviewed retrospectively. There were 34 patients in the
pancreaticoduodenectomy (PD) group and 10 patients in the distal pancreatectomy
(DP) group. One patient received total pancreatectomy. The endocrine function was
measured using the glucose tolerance index (GTI), which was derived by dividing
daily maximum serum glucose fluctuation by daily minimum glucose. Remnant
pancreas volume (RPV) was estimated by considering pancreas body and tail as a
column, and head as an ellipsoid, respectively. The pancreatic atrophic index
(PAI) was defined as the ratio of pancreatic duct width to total pancreas width.
Representative indices of each patient were compared before and after resection
up to 2 years postoperatively.The area under receiver operating characteristic
curve of GTI for diagnosing DM was 0.823 (95% confidence interval, 0.699-0.948, P
< .001). Overall, GTI increased on postoperative day 1 (POD#1, mean +/- standard
deviation, 1.79 +/- 1.40 vs preoperative, 1.02 +/- 1.41; P = .001), and then
decreased by day 7 (0.89 +/- 1.16 vs POD#1, P < .001). In the PD group, the GTI
on POD#14 became lower than preoperative (0.51 +/- 0.38 vs 0.96 +/- 1.37; P =
.03). PAI in the PD group was significantly lower at 1 month postoperatively
(0.22 +/- 0.12 vs preoperative, 0.38 +/- 0.18; P < .001). In the PD group, RPV
was significantly lower at 1 month postoperatively (25.3 +/- 18.3 cm vs
preoperative, 32.4 +/- 20.1 cm; P = .02), due to the resolution of pancreatic
duct dilatation. RPV of the DP group showed no significant change. GTI was
negatively related to RPV preoperatively (r = -0.317, P = .04), but this
correlation disappeared postoperatively (r = -0.044, P = .62).Pancreatic
endocrine functional deterioration in pancreatic adenocarcinoma patients may in
part be due to pancreatic duct obstruction and dilatation caused by the tumor.
After resection, this proportion of endocrine insufficiency is corrected.
PMID- 28700498
TI - Diagnostic value of long noncoding RNAs for hepatocellular carcinoma: A PRISMA
compliant meta-analysis.
AB - BACKGROUND: Increasing evidences have shown that long noncoding RNAs (lncRNAs)
are involved in cancer diagnosis and prognosis. However, the overall diagnostic
accuracy of lncRNAs for hepatocellular carcinoma (HCC) remains unclear. Herein,
we perform a meta-analysis to assess diagnostic value of lncRNAs for HCC.
METHODS: The online PubMed, Cochrane, Web of Science, and Embase database were
searched for eligible studies published until October 5, 2016. Study quality was
evaluated with the Quality Assessment for Studies of Diagnostic Accuracy
(QUADAS). All statistical analyses were conducted with Stata 12.0 and Meta-Disc
1.4. RESULTS: We included 19 studies from 10 articles with 1454 patients with HCC
and 1300 controls. The pooled sensitivity, specificity, positive likelihood ratio
(PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and AUC for
lncRNAs in the diagnosis of HCC were 0.83 (95% confidence interval [CI]: 0.76
0.88), 0.80 (95% CI: 0.73-0.86), 4.2 (95% CI: 3.00-5.80), 0.21 (95% CI: 0.15
0.31), 20 (95% CI: 11-34), and 0.88 (95% CI: 0.85-0.91), respectively.
Additionally, the diagnostic value of lncRNAs varied based on sex ratio of cases
and characteristics of methods (specimen type and reference gen). CONCLUSION:
This meta-analysis suggests lncRNAs show a moderate diagnostic accuracy for HCC.
However, prospective studies are required to confirm its diagnostic value.
PMID- 28700499
TI - Cerebrovascular risk factors for patients with cerebral watershed infarction: A
case-control study based on computed tomography angiography in a population from
Southwest China.
AB - To determine cerebrovascular risk factors for patients with cerebral watershed
infarction (CWI) from Southwest China.Patients suffering from acute ischemic
stroke were categorized into internal CWI (I-CWI), external CWI (E-CWI), or non
CWI (patients without CWI) groups. Clinical data were collected and degrees of
steno-occlusion of all cerebral arteries were scored. Arteries associated with
the circle of Willis were also assessed. Data were compared using Pearson chi
squared tests for categorical data and 1-way analysis of variance with Bonferroni
post hoc tests for continuous data, as appropriate. Multivariate binary logistic
regression analysis was performed to determine independent cerebrovascular risk
factors for CWI.Compared with non-CWI, I-CWI had higher degrees of steno
occlusion of the ipsilateral middle cerebral artery, ipsilateral carotid artery,
and contralateral middle cerebral artery. E-CWI showed no significant
differences. All the 3 arteries were independent cerebrovascular risk factors for
I-CWI confirmed by multivariate binary logistic regression analysis. I-CWI had
higher degrees of steno-occlusion of the ipsilateral middle cerebral artery
compared with E-CWI. No significant differences were found among arteries
associated with the circle of Willis.The ipsilateral middle cerebral artery,
carotid artery, and contralateral middle cerebral artery were independent
cerebrovascular risk factors for I-CWI. No cerebrovascular risk factor was
identified for E-CWI.
PMID- 28700500
TI - Formation of the calcarine sulcus: a potential marker to predict the progression
in utero of isolated mild fetal ventriculomegaly.
AB - Our previous study confirmed the negative association between the development of
calcarine sulcus and the width of lateral ventricles. The purpose of current
study was to evaluate the reliability of calcarine sulcus depth in the 2nd
trimester to predict the prenatal enlargement of lateral ventricle in fetuses
with isolated mild fetal ventriculomegaly (IMVM).This study used a retrospective
cohort study design. A total of 97 pregnant women with IMVM diagnosed between 20
and 26 weeks' gestation returned for a 2nd examination at 30 to 32 weeks. Lateral
ventricular size and calcarine sulcus depth were acquired from ultrasonography
and magnetic resonance imaging (MRI) scans, respectively. Progression was defined
as the process of developing from a lower group toward a higher (<10 mm, 10-12
mm, 13-15 mm, and >=16 mm).Significant correlation was observed between calcarine
sulcus depth and ventricular measurements at the 2nd scan (r = -0.71, P < .0001).
Receiver-operating characteristic curves showed that calcarine sulcus depth (area
under curve [AUC] = 0.83, 95% confidence interval [CI] = 0.74-0.92) had the best
diagnostic performance in predicting the prenatal progression, as compared with
lateral ventricle width (AUC = 0.69, 95%CI = 0.54-0.84) and gestational age (AUC
= 0.70, 95%CI = 0.57-0.83) at the initial scan. The cutoff value for calcarine
sulcus depth was 3.3 mm, with the corresponding sensitivity and specificity were
75.0% and 81.3%, respectively. Multivariate analyses showed that calcarine sulcus
depth >=3.3 mm (odds ratio = 0.09, 95%CI = 0.02-0.38, P = .001) was an
independent predictor of the prenatal progression.For IMVM, calcarine sulcus
depth might be a powerful marker to identify subjects at higher risk for worse
prenatal progression.
PMID- 28700501
TI - Metformin is associated with fewer major adverse cardiac events among patients
with a new diagnosis of type 2 diabetes mellitus: A propensity score-matched
nationwide study.
AB - Early type 2 diabetes mellitus (DM) may only require lifestyle modifications for
glycemic control without the need for oral hypoglycemic agents (OHAs). Metformin
is believed to improve cardiovascular outcomes in patients with DM, and it is
considered to be a first-line therapy. However, it is unclear whether metformin
is beneficial for patients with a new diagnosis of DM compared to those who do
not need OHAs for glycemic control.Data were obtained from a population-based
health care database in Taiwan. Patients with a new diagnosis of DM were enrolled
if they received metformin monotherapy only between 1999 and 2010. A 4:1
propensity score-matched cohort of patients with a new diagnosis of DM who did
not take OHAs or insulin during follow-up was also enrolled. The primary study
endpoint was the occurrence of major adverse cardiovascular events (MACEs). The
time to the endpoints was compared between groups using Cox proportional hazards
models.A total of 474,410 patients with DM were enrolled. During a mean 5.8 years
of follow-up, the incidence of MACEs was 1.072% (1072 per 100,000 person-years)
in the metformin monotherapy group versus 1.165% in the lifestyle modification
group (those who did not take OHAs) (P < .001). After adjusting for confounders,
metformin independently protected the DM patients from MACEs (hazard ratio: 0.83,
P < .001). The metformin group also had an improved MACE-free survival profile
from year 1 to year 12 (P < .001).In addition to lifestyle modifications, the
patients with a new diagnosis of DM treated with metformin monotherapy had a
lower MACE rate than those who did not take OHAs. Our findings suggest that
metformin may be given early to patients with a new diagnosis of DM, even when
they do not need OHAs for glycemic control.
PMID- 28700502
TI - Adverse cardiovascular events associated with biodegradable polymer drug-eluting
stents and durable polymer everolimus-eluting stents: A systematic review and
meta-analysis of 10 randomized controlled trials.
AB - BACKGROUND: Controversies have been observed among network meta-analyses
comparing biodegradable polymer drug-eluting stents (BP-DES) with durable polymer
drug-eluting stents (DP-DES). We aimed to compare the adverse cardiovascular
events associated with BP-DES and durable polymer everolimus-eluting stents (DP
EES) using a large number of patients obtained from randomized controlled trials
(RCTs). METHODS: Electronic databases were searched for randomized trials
comparing BP-DES with DP-EES. Adverse cardiovascular outcomes observed between 6
months and 3 years were considered as the clinical endpoints in this analysis.
Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated and the
pooled analyses were performed with RevMan 5.3 software. All authors had full
access to the data, and they have read and agreed to the manuscript as written.
RESULTS: Ten trials involving a total number of 13,218 patients (7451 patients
treated by BP-DES and 5767 patients treated by DP-EES) were included. No
significant difference was observed when analyzing mortality and myocardial
infarction between BP-DES and DP-EES with OR 1.08, 95% CI 0.87-1.34, P = .47 and
OR 1.04, 95% CI 0.84-1.28, P = .72 respectively. Target vessel revascularization,
target lesion revascularization, major adverse cardiac events, and stroke were
also not significantly different with OR 1.11, 95% CI 0.92-1.33, P = .28; OR
1.11, 95% CI 0.94-1.33, P = .22; OR 1.12, 95% CI 0.99-1.27; P = .07; and OR 1.13,
95% CI 0.69-1.84; P = .62 respectively. In addition, total stent thrombosis (ST)
was similarly reported between BP-DES and DP-EES with OR 0.85, 95% CI 0.59-1.21;
P = .37. However, even if BP-DES were associated with a higher rate of definite
ST with OR 1.69, 95% CI 0.92-3.08, P = .09 and DP-EES were associated with a
higher rate of probable ST with OR 0.67, 95% CI 0.38-1.17, P = .16, these results
were not statistically significant. CONCLUSIONS: Between 6 months and 3 years, BP
DES were similar in terms of cardiovascular outcomes compared to DP-EES. However,
further long-term follow-up research is recommended.
PMID- 28700503
TI - MiR-210 and miR-155 as potential diagnostic markers for pre-eclampsia
pregnancies.
AB - Pre-eclampsia (PE) is one of the leading causes of maternal and neonatal
morbidity and mortality. In recent years, many studies have shown that microRNAs
(miRNA) play important roles in the development of PE. However, the molecular
pathogenesis of PE remains unknown.In the present study, we performed a case
control study to verify the differential expression of 4 candidate miRNAs (miR
210, miR-155, miR-125b-5p, and miR-125a-5p) in 20 PE pregnancies and 20 healthy
pregnancies. The real-time quantitative reverse transcriptase-polymerase chain
reaction has been utilized to estimate the Ct values in both groups.Our results
have shown that miR-210 and miR-155 were upregulated in serum of PE pregnancies,
which suggest a potential association between these 2 miRNAs and the pathogenesis
of PE. Further studies showed that the area under the receiver operating
characteristic curve (AUC) of miR-210 and miR-155 were 0.750 and 0.703,
respectively. The AUC of the expression ratio of miR-210 (serum/urine) and miR
155 (serum/urine) were 0.761 and 0.718, respectively. Moreover, 24-hour urine
proteins have positive correlation with urine miR-210 and miR-155.Our findings
indicated that serum miR-210 and miR-155 could be 2 sensitivity and specificity
biomarkers for the diagnosis of PE while urine miR-210 and miR-155 both could be
used to evaluate the severity of kidney injury. Using these miRNAs may provide a
novel diagnosis method for identifying pregnant women who are at risk for
developing PE.
PMID- 28700504
TI - Silent presentation of multiple metastasis Burkitt lymphoma in a child: A case
report and review of the literature.
AB - RATIONALE: The Burkitt lymphoma (BL) is a very aggressive B-cell non-Hodgkin's
lymphoma. It accounts for 34% of lymphoma cases in children. PATIENT CONCERNS: We
present the case of a 6-year-old boy diagnosed with BL, who presented multiple
contrasting elements of the disease: silent symptomatology, without involvement
of the bone marrow at first, but with multiorgan infiltration and a fast
evolution, despite starting the treatment shortly after the symptoms appeared.
DIAGNOSES: He was diagnosed with BL after immunophenotyping from the pleural
fluid. INTERVENTIONS: After a week from admission, chemotherapy was initiated
according to protocol NH-BFM therapeutic group III-cytoreductive phase in the
acute care ward and subsequently the AA 24 treatment. OUTCOMES: Following the
treatment, the patient developed medullary aplasia and cutaneous toxicity. The
patient's general state remained severe during the hospitalization. LESSONS: Even
though the prognosis of BL has improved over time (up to 90% survival rate), in
this case the evolution was unfavorable. In our patient, the symptoms appeared
abruptly. They appeared late in the phase of multiple-organ dissemination, which
generated the pessimistic prognosis.
PMID- 28700505
TI - Sepsis due to Streptococcus pneumoniae associated with secondary hemophagocytic
lymphohistiocytosis in a splenectomized patient for spherocytosis: A case report.
AB - RATIONALE: Hemophagocytic lymphohistiocytosis (HLH) is a syndrome that is
characterized by an inappropriate hyperinflammatory immune response - primary, as
a consequence of a genetic defect of NK cells and cytotoxic T lymphocytes or -
secondary, in the progression of infections, rheumatic or autoimmune diseases,
malignancies or metabolic diseases. PATIENT CONCERNS: We present the case of a
secondary HLH due to Streptococcus pneumoniae infection in a splenectomised
patient for spherocytosis, a 37-year-old patient who was splenectomised in
childhood for spherocytosis, without immuneprophylaxis induced by
antipneumococcal vaccine. OUTCOMES: He developed a severe pneumococcal sepsis
associated with secondary HLH, with unfavorable outcome and death. LESSONS: To
our knowledge, just 2 similar cases had been published in the literature, none in
which the secondary HLH was the consequence of an invasive pneumococcal infection
in a splenectomized patient for spherocytosis, and the association of splenectomy
with HLH is surprizin.
PMID- 28700506
TI - Effectiveness of corticosteroid injections in adhesive capsulitis of shoulder: A
meta-analysis.
AB - BACKGROUND: Primary adhesive capsulitis is mainly characterized by spontaneous
chronic shoulder pain and the gradual loss of shoulder motion. The main treatment
for adhesive capsulitis is a trial of conservative therapies, including
analgesia, exercise, physiotherapy, oral nonsteroidal anti-inflammation drugs,
and intra-articular corticosteroid injections. Previously, it was reported that
intra-articular corticosteroid lead to fast pain relief and improvement of range
of motion (ROM). The objective of this study was to determine whether
corticosteroid injections would lead to better pain relief and greater
improvement in ROM. METHODS: We searched PubMed, Medline, and the Cochrane
library. We included 5 articles of the 1166 articles identified. Totally
injection group included 115 patients and placebo group included 110 patients. We
calculated the weighted mean differences to evaluate the pain relief as the
primary outcome. We determined the ROM as the secondary outcome. Study quality
was evaluated using the 12-item scale. We also used the criteria of the Grading
of Recommendations Assessment, Development and Evaluation to evaluate the quality
of evidence. RESULTS: In total, 5 studies were included, 4 of which were
randomized clinical trials, with a sample size of 225 patients with adhesive
capsulitis of the shoulders. The overall pooled data demonstrated that, compared
with placebo as control treatment, intra-articular corticosteroid injections were
more effective in reducing the pain score at 0 to 8 weeks, but there was no
difference between the injection group and the control group at 9 to 24 weeks.
Improvement of ROM in the injection group was greater than that of the control
group both at 0 to 8 and 9 to 24 weeks. CONCLUSIONS: Intra-articular
corticosteroid injections were more effective in pain relief in the short term,
but this pain relief did not sustain in the long term. Intra-articular
corticosteroid injection resulted in greater improvement in passive ROM both in
the short and the long terms.
PMID- 28700507
TI - Pramipexole-induced limb dystonia and its associated complex regional pain
syndrome in idiopathic Parkinson's disease: A case report.
AB - RATIONALE: This case may be due to basal ganglia dysfunction, which was probably
caused by abnormal activation of dopamine 1-like receptor (D1R) boosted by
pramipexole binding on dopamine 3-like receptor (D3R) in a situation where D3R
was overexpressed by the chronic treatment of L-dopa. PATIENT CONCERNS: Striatal
hand and foot deformities. DIAGNOSES: Striatal hand and foot deformities with
CRPS. INTERVENTIONS: Steroid treatemnt and withdrawal of the pramipexole.
OUTCOMES: Recovered significantly. LESSONS: Since the degree of overexpression of
D3R is increased in a high dose of pramipexole, for patients with PD who are
treated with L-dopa chronically, a new use of pramipexole and an increase in dose
to alleviate the symptoms of PD should be implemented with caution while closely
observing the occurrence of drug-induced complications such as dystonia and CRPS.
PMID- 28700508
TI - Hospitals' use of hospitalists: Implications for financial performance.
AB - BACKGROUND: Hospitalists, or physicians specializing in hospital-based practice,
have grown significantly since they were first introduced in the United States in
the mid-1990s. Prior studies on the impact of hospitalists have focused on costs
and length of stay. However, there is dearth of research exploring the
relationship between hospitals' use of hospitalists and organizational
performance. PURPOSE: Using a national longitudinal sample of acute care
hospitals operating in the United States between 2007 and 2014, this study
explores the impact of hospitalists staffing intensity on hospitals' financial
performance. METHODOLOGY: Data sources for this study included the American
Hospital Association Annual Survey, the Area Health Resources File, and the
Centers for Medicare & Medicaid Services' costs reports and Case Mix Index files.
Data were analyzed using a panel design with facility and year fixed effects
regression. RESULTS: Results showed that hospitals that switched from not using
hospitalists to using a high hospitalist staffing intensity had both increased
patient revenues and higher operating costs per adjusted patient day. However,
the higher operating costs from high hospitalist staffing intensity were offset
by increased patient revenues, resulting in a marginally significant increase in
operating profitability (p < .1). PRACTICE IMPLICATIONS: These findings suggest
that the rise in the use of hospitalists may be fueled by financial incentives
such as increased revenues and profitability in addition to other drivers of
adoption.
PMID- 28700509
TI - Does physician leadership affect hospital quality, operational efficiency, and
financial performance?
AB - BACKGROUND: With payers and policymakers' focus on improving the value (health
outcomes achieved per health care dollar spent) of health care delivery,
physicians are increasingly taking on senior leadership/management positions in
health care organizations (Carsen & Xia, 2006). Little research has been done to
understand the impact of physician leadership on the delivery of care. PURPOSE:
The aim of this study was to examine whether hospital systems led by physicians
were associated with better U.S. News and World Report (USNWR) quality ratings,
financial performance, and operating efficiency as compared with those led by
nonphysician managers. METHODOLOGY: Cross-sectional analysis of nationally
representative data from Medicare Cost Reports and the USNWR on the 115 largest
U.S. hospitals was performed. Bivariate analysis of physician-led and non
physician-led hospital networks included three categories: USNWR quality ratings,
hospital volume, and financial performance. Multivariate analysis of hospital
leadership, percent operating margin, inpatient days per hospital bed, and
average quality rating was subsequently performed. RESULTS: Hospitals in
physician-led hospital systems had higher quality ratings across all specialties
and more inpatient days per hospital bed than did non-physician-led hospitals;
however, there were no differences in the total revenue or profit margins between
the groups. Physician leadership was independently associated with higher average
quality ratings and inpatient days per bed. CONCLUSIONS: Large hospital systems
led by physicians in 2015 received higher USNWR ratings and bed usage rates than
did hospitals led by nonphysicians, with no differences in financial performance.
This study suggests that physician leaders may possess skills, qualities, or
management approaches that positively affect hospital quality and the value of
care delivered. PRACTICE IMPLICATIONS: Hospital quality and efficiency ratings
vary significantly and can impact consumer decisions. Hospital systems may
benefit from the presence of physician leadership to improve the quality and
efficiency of care delivered to patients. In addition, medical education should
help prepare physicians to take on leadership roles in hospitals and health
systems.
PMID- 28700510
TI - Changes in the Muscle Activity of Gymnasts During a Handstand on Various
Apparatus.
AB - Gymnasts perform handstands on various apparatus, both in stable and unstable
conditions. Such performances require specific muscle activation, which should
differ depending on the condition and expertise of the gymnast. Therefore, the
aim of the study was to evaluate 1) the difference in electromyography (EMG)
between handstands performed on three apparatus (floor, rings and parallel bars);
and 2) the difference between young and well-trained adult gymnasts. Ten adult
(25 +/- 3.94 years) and 15 young (13.9 +/- 0.7 years) gymnasts participated in
the study. We investigated EMG amplitude in thirteen muscles normalized by
arbitrary angle maximal isometric voluntary contraction (Normalized Root Mean
Square, NRMS). In comparison to the handstand on the floor (61 +/- 28%), the
wrist flexor muscles of gymnasts exhibited a decreased NRMS on the parallel bars
(44 +/- 25%; p = 0.017) and rings (46 +/- 32%; p = 0.029), whereas no changes
were observed in the triceps brachii. The rest of the investigated muscles showed
a higher NRMS in rings. Differences between young and adult gymnasts were seen in
the triceps brachii and anterior deltoid muscles, where more experienced gymnasts
showed 19.1% (p = 0.014) and 17.6% (p = 0.048) lower NRMS, respectively. The
different gymnastic apparatus led to specific muscle activation. This activation
predominantly depended on hand support conditions, which alternated the primary
wrist strategy of the handstand balance control, and in consequence, the
activation of other muscles controlling balance. Training focused on the
development of motor control and strength of the anterior deltoid, pectoralis
major, latissimus dorsi, biceps brachii, and trapezius descendent muscles in
order to improve handstand performance.
PMID- 28700511
TI - Quantifying Changes in Squat Jump Height Across a Season of Men's Collegiate
Soccer.
AB - Sams, ML, Sato, K, DeWeese, BH, Sayers, AL, and Stone, MH. Quantifying changes in
squat jump height across a season of men's collegiate soccer. J Strength Cond Res
32(8): 2324-2330, 2018-The purposes of this study were to examine the
effectiveness of an athlete monitoring program in managing athlete neuromuscular
fatigue across a men's collegiate soccer season as measured by changes in squat
jump (SJ) height and to compare possible changes with the session rating of
perceived exertion (sRPE) training load (TL). Eighteen outfield Division I men's
college soccer players performed SJ testing before each game of the fall season
in addition to a baseline measurement at the start of preseason. The athletes
provided sRPE values after all training sessions, weight-training, and games.
Linear mixed modeling was used to compare changes in SJ height across the season
with the baseline, and a correlation coefficient and single-lag cross-correlation
coefficient were calculated between TL and changes in SJ height. No statistically
significant decreases in SJ height occurred across the season, although a
moderate practical decline occurred after the preseason (-1.6 cm, effect size =
0.70). The correlation between TL and changes in SJ height was statistically
nonsignificant, whereas the cross-correlation was significant (r = 0.18, p = 0.48
and r = 0.55, p = 0.02, respectively). The athlete monitoring program was
successful in managing the athletes' neuromuscular fatigue across the season as
evidenced by the maintenance of SJ height and positive relationship between TL
and changes in SJ height. Thus, SJ monitoring may serve as a useful fatigue
monitoring tool for collegiate soccer athletes. Future study is needed, relating
changes in vertical jump performance to other markers of athlete preparedness and
performance.
PMID- 28700512
TI - Influence Of Morphology And Strength On Front Crawl Swimming Speed In Junior And
Youth Age Group Swimmers.
AB - OBJECTIVES: this study, conducted in two male age groups, was aimed at analysing
the influence of body properties, dry-land strength and swimming strength on 50 m
crawl (VCrawl). METHODS: We examined two competitive groups, Youth (20.6 +/-
1.05), and Junior, (17.3 +/- 0.59), through: a. (lean) body mass (BM and LBM),
(total) body height (BH and TBL) and arm span (AS); b. counter movement jump
(CMJ) and maximum isometric strength of elbow and knee joints; c. tethered crawl
strength. We hypothesized that a higher relationship of strength indices in
younger swimmers in VCrawl and tethered swimming would be a better sprint
performance predictor. RESULTS: the Junior group revealed a significant
relationship between somatic traits (BM r = 0.63; BH r = 0.55; TBL r = 0.58; AS r
= 0.52 with p < 0.05 LBM r = 0.78; with p < 0.01) and VCrawl, whereas such
interplay was not found in the Youth group. General dry-land strength indices CMJ
[cm], CMJ [J] or isometric strength of knee joint muscle flexors and extensors (r
= 0.57; r = 0.69; r = 0.56; r = 0.57, respectively) also significantly correlated
with VCrawl only in the Junior group. The Junior group's tethered swimming
strength had a higher but not significant relationship with VCrawl. The Youth
group instead achieved significantly higher VCrawl and stroke rate (SR). The SR
revealed (r = 0.41, p= 0.014) a relationship with VCrawl only after combination
of both groups. CONCLUSIONS: this study demonstrates a better strength
relationship with VCrawl in the younger Junior group. In the future, evaluation
of sprint swimming aptitudes, besides on the basis of somatic traits and
properties of dry-land or water strength measurement, should be complemented by
measurements of real sprint swimming technique parameters.
PMID- 28700513
TI - Sled Towing Acutely Decreases Acceleration Sprint Time.
AB - Wong, MA, Dobbs, IJ, Watkins, C, Barillas, SR, Lin, A, Archer, DC, Lockie, RG,
Coburn, JW, and Brown, LE. Sled towing acutely decreases acceleration sprint
time. J Strength Cond Res 31(11): 3046-3051, 2017-Sled towing is a common form of
overload training in sports to develop muscular strength for sprinting. This type
of training leads to acute and chronic outcomes. Acute training potentially leads
to postactivation potentiation (PAP), which is when subsequent muscle performance
is enhanced after a preload stimulus. The purpose of this study was to determine
differences between rest intervals after sled towing on acute sprint speed.
Twenty healthy recreationally trained men (age = 22.3 +/- 2.4 years, height =
176.95 +/- 5.46 cm, mass = 83.19 +/- 11.31 kg) who were currently active in a
field sport twice a week for the last 6 months volunteered to participate. A
maximal 30-meter (m) baseline (BL) body mass (BM) sprint was performed (with
splits at 5, 10, 20, and 30 m) followed by 5 visits where participants sprinted
30 m towing a sled at 30% BM then rested for 2, 4, 6, 8, or 12 minutes. They were
instructed to stand still during rest times. After the rest interval, they
performed a maximal 30-m post-test BM sprint. Analysis of variance (ANOVA)
revealed that post sled tow BM sprint times (4.47 +/- 0.21 seconds) were less
than BL times (4.55 +/- 0.18 seconds) on an individualized rest interval basis. A
follow-up 2 * 4 ANOVA showed that this decrease occurred only in the acceleration
phase over the first 5 m (BL = 1.13 +/- 0.08 seconds vs. Best = 1.08 +/- 0.08
seconds), which may be the result of PAP and the complex relationship between
fatigue and potentiation relative to the intensity of the sled tow and the rest
interval. Therefore, coaches should test their athletes on an individual basis to
determine optimal rest time after a 30-m 30% BM sled tow to enhance acute sprint
speed.
PMID- 28700514
TI - Low-Volume High-Intensity Interval Versus Continuous Endurance Training: Effects
on Hematological and Cardiorespiratory System Adaptations in Professional Canoe
Polo Athletes.
AB - Sheykhlouvand, M, Gharaat, M, Khalili, E, Agha-Alinejad, H, Rahmaninia, F, and
Arazi, H. Low-volume high-intensity interval versus continuous endurance
training: effects on hematological and cardiorespiratory system adaptations in
professional canoe polo athletes. J Strength Cond Res 32(7): 1852-1860, 2018-The
aim of this study was to compare the effect of 2 paddling-based high-intensity
interval training (HIIT) and continuous endurance training (CET) on
hematological, immunological, and cardiorespiratory adaptations in professional
canoe polo athletes. A total of 21 male canoe polo athletes were randomly divided
into 1 of 3 groups (N = 7): (a) HIIT with variable intensity (VIHIIT) (6 * 60
seconds at 100, 110, 120, 130, 130, 130, 120, 110, 100% vV[Combining Dot
Above]O2peak from first to ninth session, respectively, 1:3 work to recovery
ratio); (b) HIIT with variable volume (VVHIIT) (6, 7, 8, 9, 9, 9, 8, 7, 6
repetitions/session from first to ninth session, respectively) * 60 seconds at
lowest velocity that elicited V[Combining Dot Above]O2peak (vV[Combining Dot
Above]O2peak), 1:3 work to recovery ratio); and (c) the CET group performed 3
times * 60 minutes paddling sessions (75% vV[Combining Dot Above]O2peak) per week
for 3 weeks. Significant increases in V[Combining Dot Above]O2peak (ml.kg.min)
(VIHIIT = 7.6%, VVHIIT = 6.7%), ventilation (V[Combining Dot Above]E) at
V[Combining Dot Above]O2peak (VIHIIT = 11.5%, VVHIIT = 15.2%), respiratory
frequency (Rf) at V[Combining Dot Above]O2peak (VVHIIT = 21.1%), V[Combining Dot
Above]O2 at ventilatory threshold (VT) (VIHIIT = 10.5%, VVHIIT = 25.1%),
V[Combining Dot Above]E at VT (VIHIIT = 12.4%, VVHIIT = 34.0%), tidal volume at
VT (VIHIIT = 11.7%, VVHIIT = 33.3%), Rf at VT (VIHIIT = 9.7%), V[Combining Dot
Above]E/V[Combining Dot Above]O2 at VT (VVHIIT = 13.1%), V[Combining Dot
Above]O2/heart rate (HR) at VT (VIHIIT = 12.9%, VVHIIT = 21.4%), and V[Combining
Dot Above]E/HR at VT (VIHIIT = 7.8%, VVHIIT = 27.2%) were seen compared with
pretraining. Training interventions resulted in significant increases in mean
platelet volume (VIHIIT = 2.7%, VVHIIT = 1.9%), mean corpuscular hemoglobin
concentration (CET = 3.3%), and significant decrease in red blood cell
distribution width (VVHIIT = -4.3), and cell numbers of lymphocyte (CET = -27.1)
compared with pretraining. This study demonstrated that paddling-based HIIT
enhances aerobic capacity and respiratory makers, without negatively affecting
the immune system over 3 weeks.
PMID- 28700515
TI - Mechanical, metabolic, and perceptual acute responses to different set
configurations in full squat.
AB - This study aimed to compare mechanical, metabolic, and perceptual responses
between two traditional (TR) and four cluster (CL) set configurations. In a
counterbalanced randomized order, 11 men were tested with the following protocols
in separate sessions (sets * repetitions [inter-repetition rest]): TR1: 3*10 [0
s]; TR2: 6*5 [0-s]; CL1: 3*10 [10-s]; CL2: 3*10 [15-s]; CL3: 3*10 [30-s]); CL4:
1*30 [15-s]). The exercise (full-squat), number of repetitions (30), inter-set
rest (5 min), and resistance applied (10RM) was the same for all set
configurations. Mechanical fatigue was quantified by measuring the mean
propulsive velocity during each repetition, and the change in countermovement
jump height observed after each set and after the whole training session.
Metabolic and perceptual fatigue were assessed via the blood lactate
concentration and the OMNI perceived exertion scale measured after each training
set, respectively. The mechanical, metabolic, and perceptual measures of fatigue
were always significantly higher for the TR1 set configuration. The two set
configurations that most minimized the mechanical measures of fatigue were CL2
and CL3. Perceived fatigue did not differ between the TR2, CL1, CL2 and CL3 set
configurations. The lowest lactate concentration was observed in the CL3 set
configuration. Therefore, both the CL2 and CL3 set configurations can be
recommended because they maximize mechanical performance. However, the CL2 set
configuration presents two main advantages with respect to CL3: (1) it reduces
training session duration, and (2) it promotes higher metabolic stress, which to
some extent may be beneficial for inducing muscle strength and hypertrophy gains.
PMID- 28700516
TI - Validity of Real-Time Data Generated by a Wearable Microtechnology Device.
AB - The purpose of this study was to investigate the validity of global positioning
system (GPS) and micro-electrical-mechanical-system (MEMS) data generated in real
time through a dedicated receiver. Postsession data acted as the criterion as it
is used to plan the volume and intensity of future training and is downloaded
directly from the device. Twenty-five professional rugby league players completed
2 training sessions wearing an MEMS device (Catapult S5, firmware version: 5.27).
During sessions, real-time data were collected through the manufacturer receiver
and dedicated software (Openfield v1.14), which was positioned outdoors at the
same location for every session. The GPS variables included total-, low- (0-3
m.s), moderate- (3.1-5 m.s), high- (5.1-7 m.s), and very high-speed (>7.1 m.s)
distances. Micro-electrical-mechanical-system data included total session
PlayerLoad. When compared to postsession data, mean bias for total-, low-,
moderate-, high-, and very high-speed distances were all trivial, with the
typical error of the estimate (TEE) small, small, trivial, trivial and small,
respectively. Pearson correlation coefficients for total-, low-, moderate-, high-
and very-high-speed distances were nearly perfect, nearly perfect, perfect,
perfect, and nearly perfect, respectively. For PlayerLoad, mean bias was trivial,
whereas TEE was moderate and correlation nearly perfect. Practitioners should be
confident that when interpreting real-time speed-derived metrics, the data
generated in real-time are comparable with those downloaded directly from the
device postsession. However, practitioners should refrain from interpreting
accelerometer-derived data (i.e., PlayerLoad) or acknowledge the moderate error
associated with this real-time measure.
PMID- 28700517
TI - Longitudinal Assessment of Bone Mineral Density and Body Composition in
Competitive Cyclists.
AB - Baker, BS and Reiser II, RF. A longitudinal assessment of bone mineral density
and body composition in competitive cyclists. J Strength Cond Res 31(11): 2969
2976, 2017-Competitive cycling has been associated with low bone mineral density
(BMD); however, BMD is a multifaceted issue. The purpose of this study was to
investigate how age (18-49 years), sex, USA Cycling Category (elite-4), and
racing type (road and multiple bikes), influenced body composition across a
season in competitive cyclists. February marked the preseason, where 42
participants (22 males, 20 females) completed a health history and cycling
questionnaire, 4-day dietary log and a dual-energy X-ray absorptiometry scan, and
repeated the measures 180 +/- 11 days later. Preseason BMD and Z-Scores were
within healthy ranges and similar between sexes, age groups, competition levels
and racing-type groups (p >= 0.053). Age was significantly correlated with whole
group BMD (r = 0.309; p = 0.047). Postseason analysis revealed very encouraging
findings as no significant changes in BMD or Z-Score were observed in any group
(p >= 0.067). A significant main effect for time was found in all groups as lean
mass (LM) decreased and fat mass increased across the season (p <= 0.001).
Additional analysis showed a significant time * group interaction as cat. 1
riders decreased body mass and body mass index, whereas cat. 4 riders responded
in the opposite direction (p <= 0.037). Postseason correlations highlighted
significant positive relationships between BMD and age, LM, and Kcal ingested (r
>= 0.309; p <= 0.047). The only significant negative correlate of BMD was percent
body fat (r = -0.359; p = 0.020). Armed with this information, cyclists and
coaches should aim to prioritize balance between body mass and caloric intake
while meeting the demands of training to minimize risk of cycling related low
bone mass.
PMID- 28700518
TI - Agility And Vertical Jump Performances Are Impacted By Acute Cool Exposure.
AB - Outdoor sports teams may be exposed to acute cold stress during competition,
which may affect performance. Limited research has explored the effects of cold
exposure on athletic components. The purpose of this study was to examine the
effects of an acute whole-body cool exposure on pro-agility, vertical jump, and
sprint performances. Eleven lightly clothed (~0.3 clo) and not cold acclimatized
volunteers (10/1 women/men: age 20.5 +/- 0.5 y; height 1.65 +/- 0.09 m; mass 63.3
+/- 8.9 kg; body fat 21.3 +/- 7.6%) completed performance tests in both
thermoneutral (17.2 degrees C, 36% relative humidity, Biddeford, Maine, USA) and
cool (6.1 degrees C, 72% relative humidity, Thorsmork, Iceland) ambient
temperatures. Prior to completing the performance tests, subjects engaged in a 5
min stretching routine and were subsequently exposed to either a thermoneutral or
cool ambient environment for 15 min. Performance tests included three trials of
maximal vertical jumps, and two trials of both the 36.6 m sprint and pro-agility
tests. Mean performance and lactate values were compared via paired t-tests. Pro
agility completion time was significantly (p<0.05) slower in the cool (5.63 +/-
0.33 s) than thermoneutral (5.43 +/- 0.26 s) environment. Vertical jump was
significantly (p<0.05) lower in the cool (0.36 +/- 0.07 m) than thermoneutral
(0.41 +/- 0.10 m) environment. Sprint performance and lactate values were
unaffected by the cool exposure. Brief cool exposure appears to influence agility
and vertical jump performances. Our results suggest that it would be prudent for
athletes and coaches to consider the ambient environment when preparing for
competition.
PMID- 28700519
TI - Managing Drug-Drug Interaction Between Ombitasvir, Paritaprevir/Ritonavir,
Dasabuvir, and Mycophenolate Mofetil.
AB - No drug-drug interaction study has been conducted to date for the combination of
ombitasvir, paritaprevir/ritonavir, dasabuvir (3D), and mycophenolic acid (MPA).
We here report the case of a hepatitis C virus-infected patient treated with 3D
and MPA for vasculitis. In light of the threat of drug-drug interaction, the
concentration of MPA was measured before, during, and 15 days after the end of
the 3D treatment. Similar values were found at all 3 time points, thus indicating
that there is probably no need to adapt MPA dosage to 3D.
PMID- 28700520
TI - Current Practice for Therapeutic Drug Monitoring of Biopharmaceuticals in
Rheumatoid Arthritis.
AB - The treatment of rheumatoid arthritis (RA) has largely improved in the
biopharmaceutical era. These compounds, primarily tumor necrosis factor (TNF)
inhibitors, are effective, but some patients may show poor response, sometimes
because of the presence of antidrug antibodies (ADAs). In some instances,
clinicians may increase or taper the dose depending on the clinical response.
Besides the current clinical-based practice, a tailored strategy based on drug
monitoring has emerged as a way to improve the use of these drugs. However, the
relevance of this therapeutic drug monitoring (TDM) of biopharmaceuticals in RA
is still unknown. In this literature review, we examine the most relevant
articles dealing with the concentration-response relationship, ADA detection and
pharmacokinetics in RA patients receiving biopharmaceuticals. A concentration
response relationship was clearly established for TNF inhibitors. Moreover, ADA
positivity was associated with low drug concentrations, poor clinical outcome,
and reduced drug survival for TNF-inhibitor monoclonal antibodies. Concomitant
use of disease-modifying antirheumatic drugs, especially methotrexate, is
associated with good clinical outcome, increased drug concentrations, and reduced
immunogenicity. Strategies based on TDM of TNF inhibitors seem promising for RA,
but randomized controlled trials are required to support this. A concentration
response relationship may exist with tocilizumab, and immunogenicity seems rare.
Finally, the relevance of TDM for RA patients receiving rituximab and abatacept
remains unclear.
PMID- 28700521
TI - Effect of CYP3A4 and CYP3A5 Genetic Polymorphisms on the Pharmacokinetics of
Sirolimus in Healthy Chinese Volunteers.
AB - BACKGROUND: Sirolimus is a promising immunosuppressive drug for preventing the
rejection of organ transplants. However, inter-individual variability in
sirolimus pharmacokinetics causes adverse drug reactions, compromising
therapeutic efficacy. Sirolimus is primarily metabolized by cytochrome CYP3A4 and
CYP3A5. This study aimed to clarify the effect of CYP3A genetic polymorphisms,
including the CYP3A4*1G and CYP3A5*3 polymorphisms, on the pharmacokinetics of
sirolimus. METHODS: Thirty-one healthy Chinese volunteers were included in this
study. Their genotypes were determined using the Sequenom MassARRAY iPLEX
platform, and blood sirolimus concentrations at different time points were
analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The
pharmacokinetic parameters were calculated using WinNonlin version 5.2 software.
RESULTS: The allele frequencies of CYP3A4*1G and CYP3A5*3 were 25.8% and 71.0%,
respectively. In CYP3A4*1G carriers (n = 13), the area under the curve AUC0-144,
AUC0-infinity, and Cmax were significantly lower (P < 0.05) than CYP3A4*1/*1
homozygous subjects (n = 18). Briefly, the AUC0-144, AUC0-infinity, and Cmax of
*1G/*1G carrier were 315.2 +/- 91.5, 372.0 +/- 108.2, and 10.2 +/- 1.6 ng/mL,
respectively, and those of *1/*1 G*1/*1 G carrier were 440.8 +/- 130.6, 537.4 +/-
167.5, and 13.7 +/- 4.3, respectively, whereas those of CYP3A4*1/*1 homozygous
subjects were 540.2 +/- 150.6, 626.6 +/- 166.9, and 19.8 +/- 7.5 ng/mL,
respectively. In CYP3A5-nonexpressing subjects (*3/*3 homozygous carriers, n =
15), the AUC0-144 and Cmax were 549.6 +/- 137.9 and 19.9 +/- 7.9 ng/mL,
respectively, and were significantly higher (P < 0.05) than the values in CYP3A5
expressing subjects (*1/*1homozygous carrier, n = 2; 314.2 +/- 129.3 and 10.3 +/-
2.2 ng/mL; *1/*3 heterozygous carrier, n = 15; 440.2 +/- 146.3 and 14.6 +/- 5.1
ng/mL, respectively). CONCLUSIONS: CYP3A4 and CYP3A5 genetic polymorphisms are
important factors affecting pharmacokinetic parameters of sirolimus. Our data
support the monitoring of blood sirolimus concentrations, especially in CYP3A5*1
and CYP3A4*1 G carriers, to ensure accurate dosing in the clinical setting.
PMID- 28700522
TI - Dried Blood Spot Sampling for Tacrolimus and Mycophenolic Acid in Children:
Analytical and Clinical Validation.
AB - BACKGROUND: Tacrolimus and mycophenolic acid (MPA) are the backbone of
immunosuppressive therapy after pediatric kidney transplantation. Dosing of these
drugs is individualized by therapeutic drug monitoring. Dried blood spot (DBS)
sampling may prove beneficial over conventional venous sampling. We aimed to
develop and clinically validate a DBS method for tacrolimus and MPA in children.
METHODS: A joint DBS liquid chromatography-mass spectrometry assay for tacrolimus
and MPA was developed. DBS-specific items included the hematocrit effect and
influence of spot volume. Subsequently, a clinical validation study among
children aged 2-18 years was performed to assess the agreement between observed
and DBS-predicted venous concentrations. Agreement of the methods was assessed
with Passing-Bablok regression, Bland-Altman plots, and quantification of the DBS
predictive performance in terms of bias (median percentage prediction error) and
precision (median absolute percentage prediction error), both should be <15%.
RESULTS: A total of 40 tacrolimus and 32 MPA samples were available from 28
children. Conversion factors were used to predict venous concentrations from DBS.
For tacrolimus, 95% of the individual ratios of predicted and observed
concentrations were within a range of 0.74-1.28, with 85% of these ratios between
0.80 and 1.20 (Bland-Altman plots). For MPA, the 95% limits of agreement
represented a broader range of 0.49-1.49%, and 72% of individual ratios were
between the 0.80 and 1.20 limits. Median percentage prediction error and median
absolute percentage prediction error were less than 15% for both drugs.
CONCLUSIONS: A DBS assay was developed for tacrolimus and MPA. Tacrolimus venous
concentrations could be adequately predicted from DBS. DBS analysis of MPA seemed
to be a semiquantitative measurement at the most when compared with conventional
plasma analysis, considering the high variability between observed and predicted
concentrations. Next, home-based DBS sampling of tacrolimus for the purpose of
therapeutic drug monitoring will be implemented into routine clinical care.
PMID- 28700523
TI - Dried Blood Spots Combined With Ultra-High-Performance Liquid Chromatography-Mass
Spectrometry for the Quantification of the Antipsychotics Risperidone,
Aripiprazole, Pipamperone, and Their Major Metabolites.
AB - BACKGROUND: Risperidone, aripiprazole, and pipamperone are antipsychotic drugs
frequently prescribed for the treatment of comorbid behavioral problems in
children with autism spectrum disorders. Therapeutic drug monitoring (TDM) could
be useful to decrease side effects and to improve patient outcome. Dried blood
spot (DBS) sample collection seems to be an attractive technique to develop TDM
of these drugs in a pediatric population. The aim of this work was to develop and
validate a DBS assay suitable for TDM and home sampling. METHODS: Risperidone, 9
OH risperidone, aripiprazole, dehydroaripiprazole, and pipamperone were extracted
from DBS and analyzed by ultra-high-performance liquid chromatography-tandem mass
spectrometry using a C18 reversed-phase column with a mobile phase consisting of
ammonium acetate/formic acid in water or methanol. The suitability of DBS for TDM
was assessed by studying the influence of specific parameters: extraction
solution, EDTA carryover, hematocrit, punching location, spot volume, and
hemolysis. The assay was validated with respect to conventional guidelines for
bioanalytical methods. RESULTS: The method was linear, specific without any
critical matrix effect, and with a mean recovery around 90%. Accuracy and
imprecision were within the acceptance criteria in samples with hematocrit values
from 30% to 45%. EDTA or hemolysis did not skew the results, and no punching
carryover was observed. No significant influence of the spot volume or the punch
location was observed. The antipsychotics were all stable in DBS stored 10 days
at room temperature and 1 month at 4 or -80 degrees C. The method was
successfully applied to quantify the 3 antipsychotics and their metabolites in
patient samples. CONCLUSIONS: A UHPLC-MS/MS method has been successfully
validated for the simultaneous quantification of risperidone, 9-OH risperidone,
aripiprazole, dehydroaripiprazole, and pipamperone in DBS. The assay provided
good analytical performances for TDM and clinical research applications.
PMID- 28700524
TI - Challenges for Detecting Valproic Acid in a Nontargeted Urine Drug Screening
Method.
AB - BACKGROUND: Valproic acid (VPA) is a widely prescribed medicine, and acute
toxicity is possible. As such, it should be included in any nontargeted urine
drug screening method. In many published liquid chromatography-electrospray
ionization-mass spectrometry (LC-ESI-MS/MS) methods, VPA is usually measured
using a pseudo-multiple reaction monitoring (MRM) transition. We investigate a
simple ultra-high-performance liquid chromatography-quadrupole time-of-flight
(QTof) approach to detect the presence of VPA with more confidence. METHODS:
Three commercially sourced VPA metabolites were characterized and added to a
nontargeted high-resolution MS urine drug screening method. All analyses were
performed on a Waters Xevo G2-XS LC-QTof in negative electrospray ionization
mode. The mass detector was operated in MS mode, and data were processed with
UNIFI software. Sixty-eight patient urine samples, which were previously
identified by a well-established gas chromatography-MS method as containing VPA,
were analyzed on the Waters Xevo G2-XS LC-QTof, to validate this approach.
RESULTS: VPA metabolite standards were characterized, and their detection data
were added to the broad drug screening library. VPA metabolites were readily
detectable in the urine of patients taking VPA. CONCLUSIONS: The inclusion of
characterized VPA metabolites provides a simple and reliable method enabling the
detection of VPA in nontargeted urine drug screening.
PMID- 28700525
TI - Extracranial Carotid Aneurysm in Takayasu Arteritis.
PMID- 28700526
TI - Urinary Macrophage Migration Inhibitory Factor as a Noninvasive Biomarker in
Pediatric Henoch-Schonlein Purpura Nephritis.
AB - PURPOSES: The aims of this study were to investigate urinary macrophage migration
inhibitory factor (MIF) levels and their clinical significance in Henoch
Schonlein purpura (HSP) children with or without nephritis (N) and to assess the
influence of steroid treatment on the urine MIF levels of HSPN patients. METHODS:
Group I comprised 35 children with HSPN who were examined twice (A before
treatment and B after steroid treatment). Group II comprised 41 children with
HSP. The control group included 32 healthy children. Urinary MIF levels were
measured via enzyme linked immunosorbent assay. The levels of serum creatinine,
blood urea nitrogen, urinary microalbumin (mAlb), and 24-hour proteinuria were
performed to determine their associations with MIF levels. RESULTS: Urinary MIF
levels were significantly higher in group I compared with group II and the
control group (P < 0.01); however, no significant difference was found between
group II and the control group (P > 0.05). Upon examination, albeit urinary MIF
concentration was significantly lower in group IB compared with group IA (P <
0.05), these concentrations were statistically higher than that of group II (P <
0.05). In addition, in the HSPN patients, the urinary MIF was positively
associated with urinary microalbumin and 24-hour proteinuria but no association
with serum creatinine and blood urea nitrogen. CONCLUSIONS: Elevated urinary MIF
levels were found to be correlated with proteinuria in pediatric HSPN. An obvious
decrease in urinary MIF concentrations among the children with HSPN was
associated with steroid treatment. Urinary MIF can be used as a noninvasive
biomarker in pediatric HSPN.
PMID- 28700527
TI - Magnetic Resonance Imaging in Psoriatic Arthritis: A Descriptive Study of
Indications, Features and Effect on Treatment Change.
AB - OBJECTIVE: The aims of this study were to describe the indications for, and
features of, axial/peripheral joint magnetic resonance imaging (MRI) in psoriatic
arthritis (PsA) and to examine the influence of MRI findings on clinical
practice. METHODS: All axial and peripheral (hand and/or foot) MRI scans on
patients attending the Toronto PsA clinic l between 2003 and 2014 were included.
Scan details were garnered from the radiologist's official report. A chart review
was performed to determine if MRI findings contributed to a change of treatment.
RESULTS: One hundred sixty-eight scans were performed on 125 patients (135 axial
and 33 peripheral). The mean age was 50.5 (SD, 11.5) years, with 51.2% being
female. Mean duration of PsA was 11.2 (SD, 10.9) years. Of the axial scans, the
majority were performed on the whole spine (excluding the sacrum) (27.4%) or the
sacroiliac joints and spine together (45.2%). The predominant indications were
for suspected inflammatory (51.1%) or degenerative (24.4%) disease. Magnetic
resonance imaging revealed inflammatory and/or structural change in 34.1% versus
54.8% with degenerative changes. In MRI axial inflammation (n = 25), the majority
(48%) had sacroiliac joint involvement, whereas 28% had inflammation at 2 or more
sites.Of the periphery, 60.6% of scans were on hands and 21.2% were on feet
alone. The main indications were for suspected subclinical synovitis (78.8%).
Inflammatory arthritis was the MRI diagnosis in 72.7%. Magnetic resonance imaging
findings influenced treatment change (n = 32) in 56.3%, but were insufficient to
effect treatment change without clinical findings (100%). CONCLUSIONS: Magnetic
resonance imaging is useful in evaluating patients with active PsA, particularly
when suspecting inflammation and radiographic findings are unhelpful. In some
cases, it can be used as an adjunct to clinical examination in determining
treatment change.
PMID- 28700528
TI - Widespread Purpura as a Presenting Manifestation of Antiphospholipid Syndrome.
PMID- 28700529
TI - Rheumatologists Modestly More Likely to Counsel Smokers in Visits Without
Rheumatoid Arthritis Control: An Observational Study.
AB - BACKGROUND: Among patients with rheumatoid arthritis (RA), smoking increases risk
of severe RA and pulmonary and cardiovascular disease. Despite this, little is
known about smoking cessation counseling by rheumatologists. OBJECTIVES: We
examined predictors of tobacco counseling in RA patients who smoke including the
effect of perceived RA control. We hypothesized that patients with controlled RA
would receive more counseling according to the competing demands model, which
explains that preventive care gaps occur as a result of competing provider,
patient, and clinic factors. METHODS: This secondary data analysis involved RA
patients with an additional cardiovascular disease risk factor identified in an
academic medical center 2004-2011. Trained abstractors assessed documented
smoking counseling and rheumatologists' impression of RA control in clinic notes.
We used multivariable logistic regression to predict having received smoking
cessation counseling, including sociodemographics and comorbidity in models.
RESULTS: We abstracted 3396 RA visits, including 360 visits (10%) with active
smokers. Perceived controlled RA was present in 31% of visits involving smokers
(39% in nonsmokers). Beyond nurse documentation, providers documented smoking
status in 39% of visit notes with smokers and smoking cessation counseling in
10%. Visits with controlled versus active RA were less likely to include
counseling (odds ratio, 0.3; confidence interval, 0.1-0.97). Counseling was more
likely in visits with prevalent cardiovascular, pulmonary, and psychiatric
disease, but decreased with obesity. CONCLUSIONS: Smoking cessation counseling
was documented in 10% of visits and was less likely when RA was controlled. Given
smoking's impact on RA and long-term outcomes, systematic cessation counseling
efforts are needed.
PMID- 28700530
TI - Retrospective Study of Patients on Etanercept Therapy for Rheumatic Diseases in
Patients With Chronic Hepatitis C Virus.
AB - OBJECTIVE: Treatment of rheumatic diseases with concurrent hepatitis C virus
(HCV) infection is a therapeutic challenge. Etanercept has no known
hepatotoxicity; however there is a concern for worsening of HCV infection-related
liver disease due to immunosuppressive action of the drug. Here, we
retrospectively assessed the safety of etanercept in rheumatologic disease in
patients with chronic HCV. METHODS: A retrospective review was conducted in
patients with chronic HCV infection who received etanercept for diagnosis of
rheumatoid arthritis and psoriatic arthritis. The primary end point was a serum
transaminase level of at least 3 times the upper limit of normal during
etanercept therapy. We also recorded HCV RNA load. RESULTS: Fourteen patients met
the inclusion criteria. Mean age was 52 (SD, 8) years. The median follow-up
period after initiation of etanercept was 105 months (range, 13-132 months).
During follow-up, 7 of 14 patients had elevation of aspartate aminotransferase
and/or alanine aminotransferase 3 times the upper limit of normal. Two of 7
patients had concomitant elevation in transaminases and increase in HCV viral
load during etanercept exposure, which could not be attributed to other
hepatotoxic disease-modifying antirheumatic drugs. In both patients, transaminase
levels normalized upon etanercept discontinuation. CONCLUSIONS: In contrast to
the majority of previous shorter-duration studies, 2 of 14 patients in our series
had possible HCV-related worsening of liver disease while on etanercept therapy.
Although no firm conclusion can be drawn, it appears that HCV infection can
worsen while on etanercept therapy, and therefore, we propose these patients
should be monitored serially.
PMID- 28700531
TI - The Influence of Income and Formal Education on Damage in Brazilian Patients With
Systemic Lupus Erythematosus.
AB - OBJECTIVE: The aim of this study was to evaluate the association of socioeconomic
status and American College of Rheumatology/Systemic Lupus International
Collaborating Clinics Damage Index (SDI) score in Brazilian patients with
systemic lupus erythematosus (SLE). METHODS: Five hundred twenty-three patients
(SLE ACR criteria) 18 years or older who were at 12 months or greater since
diagnosis were included. Socioeconomic status was assessed by per-capita income
and years of education. Race was categorized as white and nonwhite. The SDI and
Mexican SLE Disease Activity Index were used. STATISTICAL ANALYSIS: Mean +/- SD
and median were used for descriptive analysis. Student t test, Mann-Whitney U
test, chi test, and Spearman rank correlation coefficient and univariate and
multivariate regression analyses were performed. The level of significance was
set at 5% for all statistical tests. RESULTS: Ninety-six percent were female,
51.2% were nonwhite, and the mean age was 37.8 +/- 1.4 years. Disease duration
was 8.2 +/- 10.3 years and formal education was 10.2 +/- 3.5 years. Unemployment
among patients was 63.7%, with median monthly per-capita income of US $276. Mean
SDI score was 1.4 +/- 1.52, and 65.6% had some type of damage (SDI >=1). Patients
with SDI of 1 or greater had lower income (P = 0.039). Nonwhite patients had
higher SDI than did white patients (P = 0.005). The SDI presented a positive
correlation with disease duration (P < 0.001) and age (P < 0.001) and a negative
correlation with years of education (P = 0.001). Working patients had lower SDI
than did inactive ones (P <= 0.001). In a multivariate analysis, older age,
higher disease duration, nonwhite race, low income, and out-of-work profile were
associated with damage. CONCLUSIONS: Besides nonmodifiable characteristics such
as longer disease duration and older age, low income was also associated with
damage. Therefore, interventions to give adequate socioeconomic support are
necessary to improve outcome, mainly in poorer and nonwhite SLE patients.
PMID- 28700532
TI - Musculoskeletal Involvement in Hereditary Hemochromatosis.
PMID- 28700533
TI - CD103+ Dendritic Cell Function Is Altered in the Colons of Patients with
Ulcerative Colitis.
AB - BACKGROUND: Human intestinal innate myeloid cells can be divided into 3 subsets:
HLA-DRCD14 cells, HLA-DRCD103 dendritic cells (DCs), and HLA-DRCD14CD103 cells.
CD103 DCs generate Treg cells and Th17 cells in the ileum, but their function in
the colon remains largely unknown. This study characterized CD103 DCs in the
colon and investigated whether these cells are implicated in the pathogenesis of
ulcerative colitis (UC). METHODS: Normal intestinal mucosa was obtained from
intact sites of patients with colorectal cancer (n = 24). Noninflamed and
inflamed colonic tissues were obtained from surgically resected specimens of
patients with UC (n = 13). Among LinCD45HLA-DR intestinal lamina propria cells,
CD14 cells and CD103 DCs were sorted and analyzed for microRNA expression of
cytokines and toll-like receptors by quantitative real-time polymerase chain
reaction. In addition, IL-4/IL-5/IL-13/IL-17/IFN-gamma production and Foxp3
expression by naive T cells cultured with CD14 cells and CD103 DCs were analyzed.
RESULTS: CD103 DCs in the normal colon showed lower expression of toll-like
receptors and proinflammatory cytokines than CD14 cells. Coculture with naive T
cells revealed that CD103 DCs generated Treg cells. CD103 DCs from patients with
UC did not generate Treg cells, but they induced IFN-gamma-, IL-13-, and IL-17
producing CD4 T cells and showed higher expression of IL6 (P < 0.0001), IL23A (P
< 0.05), IL12p35 (P < 0.05), and TNF (P < 0.05). CONCLUSIONS: In patients with
UC, CD103 DCs show the impaired ability to generate Treg cells, but exhibit a
colitogenic function inducing Th1/Th2/Th17 responses. These findings show how
human CD103 DCs could contribute to the pathogenesis of UC.
PMID- 28700534
TI - Clinical Predictors of Future Nonadherence in Inflammatory Bowel Disease.
AB - BACKGROUND: Nonadherence to medical therapy is frequently encountered in patients
with inflammatory bowel disease (IBD). We aimed to identify predictors for future
(non)adherence in IBD. METHODS: We conducted a multicenter prospective cohort
study with adult patients with Crohn's disease (CD) and ulcerative colitis (UC).
Data were collected by means of 3-monthly questionnaires on the course of disease
and healthcare utilization. Medication adherence was assessed using a visual
analogue scale, ranging from 0% to 100%. Levels <80% were considered to indicate
nonadherence. The Brief Illness Perception Questionnaire was used to identify
illness perceptions. We used a logistic regression analysis to identify patient-
and disease-related factors predictive of nonadherence 3 months after the
assessment of predictors. RESULTS: In total, 1558 patients with CD and 1054
patients with UC were included and followed for 2.5 years. On average, 12.1% of
patients with CD and 13.3% of patients with UC using IBD-specific medication were
nonadherent. Nonadherence was most frequently observed in patients using
mesalazine (CD), budesonide (UC) and rectally administrated therapy (both CD and
UC). A higher perceived treatment control and understanding of the disease were
associated with adherence to medical therapy. Independent predictors of future
nonadherence were age at diagnosis (odds ratio [OR]: 0.99 per year), nonadherence
(OR: 26.91), a current flare (OR: 1.30) and feelings of anxiety/depression (OR:
1.17), together with an area under the receiver-operating-characteristics curve
of 0.74. CONCLUSIONS: Lower age at diagnosis, flares, feelings of anxiety or
depression, and nonadherence are associated with future nonadherence in patients
with IBD. Altering illness perceptions could be an approach to improve adherence
behavior.
PMID- 28700535
TI - Vitamin D Status Is Associated with Hepcidin and Hemoglobin Concentrations in
Children with Inflammatory Bowel Disease.
AB - BACKGROUND: Anemia, iron deficiency, and hypovitaminosis D are well-known
comorbidities in inflammatory bowel disease (IBD). Epidemiologic studies have
linked vitamin D deficiency with increased risk of anemia, and in vitro studies
suggest that vitamin D may improve iron recycling through downregulatory effects
on hepcidin and proinflammatory cytokines. METHODS: We aimed to investigate the
association of vitamin D status with inflammation, iron biomarkers, and anemia in
pediatric IBD. Cross-sectional data were obtained from N = 69 patients with IBD
aged 5 to <19 years. Iron biomarkers (ferritin, soluble transferrin receptor),
and 25-hydroxyvitamin D (25(OH)D), inflammatory biomarkers (C-reactive protein
and alpha-1-acid glycoprotein), hepcidin, and hemoglobin were collected. Iron
biomarkers were regression corrected for inflammation. Multivariable
logistic/linear models were used to examine the associations of 25(OH)D with
inflammation, iron status, hepcidin, and anemia. RESULTS: Approximately 50% of
subjects were inflamed (C-reactive protein >5 mg/L or alpha-1-acid glycoprotein
>1 g/L). Iron deficiency prevalence (inflammation-corrected ferritin <15 MUg/L or
soluble transferrin receptor >8.3 mg/L) was 67%; anemia was 36%, and vitamin D
insufficiency (25(OH)D <30 ng/mL) was 77%. In linear regression models, vitamin D
insufficiency was associated with increased hepcidin levels (beta [SE] = 0.6
[0.2], P = 0.01) and reduced hemoglobin (beta [SE] = -0.9 [0.5], P = 0.046),
controlling for age, sex, race, insurance status, body mass index for age,
inflammation, disease diagnosis (ulcerative colitis versus Crohn's disease), and
disease duration, compared with 25(OH)D >=30 ng/mL. CONCLUSIONS: Our results
suggest that concentrations of 25(OH)D >=30 ng/mL are associated with lower
hepcidin and higher hemoglobin levels. Further research is needed to clarify the
association of vitamin D with inflammation, iron status, and anemia in pediatric
IBD.
PMID- 28700536
TI - Fully implantable, battery-free wireless optoelectronic devices for spinal
optogenetics.
AB - The advent of optogenetic tools has allowed unprecedented insights into the
organization of neuronal networks. Although recently developed technologies have
enabled implementation of optogenetics for studies of brain function in freely
moving, untethered animals, wireless powering and device durability pose
challenges in studies of spinal cord circuits where dynamic, multidimensional
motions against hard and soft surrounding tissues can lead to device degradation.
We demonstrate here a fully implantable optoelectronic device powered by near
field wireless communication technology, with a thin and flexible open
architecture that provides excellent mechanical durability, robust sealing
against biofluid penetration and fidelity in wireless activation, thereby
allowing for long-term optical stimulation of the spinal cord without constraint
on the natural behaviors of the animals. The system consists of a double-layer,
rectangular-shaped magnetic coil antenna connected to a microscale inorganic
light-emitting diode (MU-ILED) on a thin, flexible probe that can be implanted
just above the dura of the mouse spinal cord for effective stimulation of light
sensitive proteins expressed in neurons in the dorsal horn. Wireless optogenetic
activation of TRPV1-ChR2 afferents with spinal MU-ILEDs causes nocifensive
behaviors and robust real-time place aversion with sustained operation in animals
over periods of several weeks to months. The relatively low-cost electronics
required for control of the systems, together with the biocompatibility and
robust operation of these devices will allow broad application of optogenetics in
future studies of spinal circuits, as well as various peripheral targets, in
awake, freely moving and untethered animals, where existing approaches have
limited utility.
PMID- 28700537
TI - Quantitative sensory testing response patterns to capsaicin- and ultraviolet-B
induced local skin hypersensitization in healthy subjects: a machine-learned
analysis.
AB - The comprehensive assessment of pain-related human phenotypes requires
combinations of nociceptive measures that produce complex high-dimensional data,
posing challenges to bioinformatic analysis. In this study, we assessed
established experimental models of heat hyperalgesia of the skin, consisting of
local ultraviolet-B (UV-B) irradiation or capsaicin application, in 82 healthy
subjects using a variety of noxious stimuli. We extended the original heat
stimulation by applying cold and mechanical stimuli and assessing the
hypersensitization effects with a clinically established quantitative sensory
testing (QST) battery (German Research Network on Neuropathic Pain). This study
provided a 246 * 10-sized data matrix (82 subjects assessed at baseline,
following UV-B application, and following capsaicin application) with respect to
10 QST parameters, which we analyzed using machine-learning techniques. We
observed statistically significant effects of the hypersensitization treatments
in 9 different QST parameters. Supervised machine-learned analysis implemented as
random forests followed by ABC analysis pointed to heat pain thresholds as the
most relevantly affected QST parameter. However, decision tree analysis indicated
that UV-B additionally modulated sensitivity to cold. Unsupervised machine
learning techniques, implemented as emergent self-organizing maps, hinted at
subgroups responding to topical application of capsaicin. The distinction among
subgroups was based on sensitivity to pressure pain, which could be attributed to
sex differences, with women being more sensitive than men. Thus, while UV-B and
capsaicin share a major component of heat pain sensitization, they differ in
their effects on QST parameter patterns in healthy subjects, suggesting a lack of
redundancy between these models.
PMID- 28700538
TI - Autonomic responses to tonic pain are more closely related to stimulus intensity
than to pain intensity.
AB - Pain serves the protection of the body by translating noxious stimulus
information into a subjective percept and protective responses. Such protective
responses rely on autonomic responses that allocate energy resources to
protective functions. However, the precise relationship between objective
stimulus intensity, subjective pain intensity, autonomic responses, and brain
activity is not fully clear yet. Here, we addressed this question by continuously
recording pain ratings, skin conductance, heart rate, and electroencephalography
during tonic noxious heat stimulation of the hand in 39 healthy human subjects.
The results confirmed that pain intensity dissociates from stimulus intensity
during 10 minutes of noxious stimulation. Furthermore, skin conductance measures
were significantly related to stimulus intensity but not to pain intensity.
Correspondingly, skin conductance measures were significantly related to alpha
and beta oscillations in contralateral sensorimotor cortex, which have been shown
to encode stimulus intensity rather than pain intensity. No significant
relationships were found between heart rate and stimulus intensity or pain
intensity. The findings were consistent for stimulation of the left and the right
hands. These results suggest that sympathetic autonomic responses to noxious
stimuli in part directly result from nociceptive rather than from perceptual
processes. Beyond, these observations support concepts of pain and emotions in
which sensory, motor, and autonomic components are partially independent
processes that together shape emotional and painful experiences.
PMID- 28700539
TI - Propranolol treatment prevents chronic central sensitization induced by repeated
dural stimulation.
AB - Migraine is currently conceptualized as a chronic disease with episodic
manifestations. In some patients, migraine attack frequency increases, leading to
chronic migraine. Daily preventive therapy is initiated to decrease attack
frequency. Propranolol, a first-line medication for migraine prophylaxis, reduces
attack frequency in nearly 50% of patients receiving it. However, the mechanisms
of its antimigraine action are unclear. We examined the effect of daily
propranolol treatment (10 mg.kg per os, 8 days) in a rat model of recurrent
activation of dural nociceptors (repeated infusion of an inflammatory soup (IS)
on the dura through a cannula every 2-3 days). Propranolol does not abort IS
induced acute cephalic mechanical allodynia but blocks the development of a
chronic cutaneous hypersensitivity upon repeated IS injections. Furthermore,
propranolol prevents (1) the elevated touch-evoked Fos expression within the
trigeminocervical complex, (2) enhanced both spontaneous activity, and evoked
responses of second-order trigeminovascular neurons, (3) elevated touch-evoked
rostral ventromedial medulla and locus coeruleus Fos expression and (4) diffuse
noxious inhibitory controls impairment, induced by repeated IS injections. Our
results suggest that propranolol exerts its prophylactic action, at least in
part, by blocking the chronic sensitization of descending controls of pain,
arising from the rostral ventromedial medulla and locus coeruleus, and in turn
preventing the maintenance of a state of facilitated trigeminovascular
transmission within the trigeminocervical complex. Assessing changes in these
brain areas has the potential to elucidate the mechanisms for migraine
transformation and to reveal novel biological and molecular targets for specific
migraine-preventive therapies.
PMID- 28700541
TI - Merck KGaA, F-Star shake on immune-oncology bispecifics.
PMID- 28700540
TI - Clinical and Radiological Presentations and Management of Blunt Splenic Trauma: A
Single Tertiary Hospital Experience.
AB - BACKGROUND Splenic injury is the leading cause of major bleeding after blunt
abdominal trauma. We examined the clinical and radiological presentations,
management, and outcome of blunt splenic injuries (BSI) in our institution.
MATERIAL AND METHODS A retrospective study of BSI patients between 2011 and 2014
was conducted. We analyzed and compared management and outcome of different
splenic injury grades in trauma patients. RESULTS A total of 191 BSI patients
were identified with a mean (SD) age of 26.9 years (13.1); 164 (85.9%) were
males. Traffic-related accident was the main mechanism of injury. Splenic
contusion and hematoma (77.2%) was the most frequent finding on initial
computerized tomography (CT) scans, followed by shattered spleen (11.1%), blush
(11.1%), and devascularization (0.6%). Repeated CT scan revealed 3 patients with
pseudoaneurysm who underwent angioembolization. Nearly a quarter of patients were
managed surgically. Non-operative management failed in 1 patient who underwent
splenectomy. Patients with grade V injury presented with higher mean ISS and
abdominal AIS, required frequent blood transfusion, and were more likely to be
FAST-positive (p=0.001). The majority of low-grade (I-III) splenic injuries were
treated conservatively, while patients with high-grade (IV and V) BSI frequently
required splenectomy (p=0.001). Adults were more likely to have grade I, II, and
V BSI, blood transfusion, and prolonged ICU stay as compared to pediatric BSI
patients. The overall mortality rate was 7.9%, which is mainly association with
traumatic brain injury and hemorrhagic shock; half of the deaths occurred within
the first day after injury. CONCLUSIONS Most BSI patients had grade I-III
injuries that were successfully treated non-operatively, with a low failure rate.
The severity of injury and presence of associated lesions should be carefully
considered in developing the management plan. Thorough clinical assessment and CT
scan evaluation are crucial for appropriate management of BSI.
PMID- 28700542
TI - Consent and engagement, security, and authentic living using wearable and mobile
health technology.
PMID- 28700544
TI - Payer coverage policies for multigene tests.
PMID- 28700545
TI - FDA deems in vitro data on mutations sufficient to expand cystic fibrosis drug
label.
PMID- 28700546
TI - Wanted: biotech for an aging population.
PMID- 28700547
TI - Public biotech in 2016-the numbers.
PMID- 28700548
TI - FDA is the wrong agency to regulate genetically engineered animals.
PMID- 28700549
TI - CRISPR-Cas9 claim sets and the potential to stifle innovation.
PMID- 28700550
TI - CAR-Ts move beyond B-cell cancers to myeloma.
PMID- 28700551
TI - Unlocking Big Data for better health.
PMID- 28700553
TI - First rounders: Jan Vilcek.
PMID- 28700552
TI - First state-approved embryonic stem cell trials in China.
PMID- 28700554
TI - Faster, deeper, smaller-the rise of antibody-like scaffolds.
PMID- 28700555
TI - An emerging model for life sciences commercialization.
PMID- 28700557
TI - Around the world in a month.
PMID- 28700556
TI - Permeability rules for antibiotic design.
PMID- 28700560
TI - AI-powered drug discovery captures pharma interest.
PMID- 28700558
TI - Algal oil productivity gets a fat bonus.
PMID- 28700561
TI - Recent patents in optogenetics and optochemistry.
PMID- 28700562
TI - Single-cell genomics for the masses.
PMID- 28700563
TI - The relationship between serum levels of prolactin and growth hormone in the
early postnatal period.
AB - BackgroundIn the neonatal period, the pituitary hormones including prolactin
(PRL) and human growth hormone (hGH) are secreted in high amounts due to immature
feedback mechanisms. As both hormones are secreted in part by the same
somatomammotrophic cells, we investigated their relationship in newborns with
respect to sex, gestational week, method of delivery, and anthropometric
data.MethodsThe serum levels of PRL and hGH were measured in blood drawn from 225
newborns. The newborn data were extracted from medical records.ResultsA positive
correlation was found between log-transformations of PRL and hGH (r=0.17; P=0.01;
n=225), with a stronger correlation in newborns whose blood samples were taken
more than 2 days after birth (r=0.42; P<0.001; n=130). Log-transformations of the
PRL/hGH ratio demonstrated a positive correlation with the gestational week
(r=0.39; P<0.001; n=200). Multiple regression analysis showed that 15% of the
variance in the logarithm of this ratio is attributed to the gestational
week.ConclusionIn newborns, serum PRL and hGH levels show a positive correlation
that can be explained by common regulatory factors or a drift phenomenon. A
higher gestational week is associated with a higher PRL/hGH ratio. Further
studies are needed to look for possible confounders and to determine the PRL-hGH
relationship in different conditions.
PMID- 28700564
TI - Long-term effects of adenotonsillectomy on serum-specific immunoglobulin E.
AB - BackgroundThe biased immune reactions of the adenotonsillar tissues are not
always reflected by the serum immunoglobulin E (IgE); thus, we hypothesize that
the systemic atopic status may not be changed after the adenotonsillectomy (AT)
in children.MethodsTwenty-five children with AT and 23 age-matched healthy
children were enrolled into this study, and followed up for ~4 years. Nasal
Symptoms Scores (NSS), Quality of Life Scores (QOLS), specific IgE (sIgE),
cytokines, and inflammatory cell were documented in all the subjects before and
after study.ResultsFourteen patients and three healthy controls had positive
serum sIgE levels (>0.35 kU/l) at the study-start that was not changed by the
study-end. Two patients and two sIgE-negative healthy controls showed the
Dermatophagoidespteronyssinus sensitization at the study-end. NSS and QOLS showed
significant improvement after the surgery in the sIgE-positive patients (P<0.05),
whereas no significant changes were found in the sIgE-negative patients (P=1.00).
In addition, the serum sIgE-negative patients showed significant increases in
interleukin (IL)-4, IL-5, and IL-10 levels in the serum (P<0.001), although no
significant differences were found post surgery (P=0.667, 0.408, and 0.714,
respectively).ConclusionsOur study showed that AT did not affect the pediatric
atopic status. The systemic atopy may be independent of the tonsillar and adenoid
tissues in children.
PMID- 28700565
TI - Nasal continuous positive airway pressure influences bottle-feeding in preterm
lambs.
AB - BackgroundIn preterm infants, the time from initiation to full oral feeding can
take weeks, which represents a very worrisome problem in neonatal medicine.
Although current knowledge suggests that oral feeding should be introduced early,
this is often delayed due to the need for prolonged nasal continuous positive
airway pressure (nCPAP). Indeed, most caregivers fear that nCPAP could disrupt
sucking-swallowing-breathing coordination and induce tracheal aspiration. The
goal of the present study was to assess the impact of nCPAP delivered by the
Infant Flow System on the physiology of sucking-swallowing-breathing coordination
during bottle-feeding in preterm lambs over 24 h.MethodsSeventeen lambs (8
control, 9 nCPAP of 6 cmH2O) born 14 days prematurely were instrumented to record
sucking, swallowing, respiration, ECG, and oxygenation. They were fed via a
nasogastric tube for the first 5 days of life until introduction of bottle
feeding every 4 h for 24 h.ResultsnCPAP increased the feeding efficiency while
maintaining higher oxygenation without any deleterious cardiorespiratory events.
However, coughs were observed in lambs under nCPAP immediately following bottle
feeding and may be related to the high milk flow in preterm
lambs.ConclusionFurther studies documenting tracheal aspirations are needed,
especially in preterm lambs under nCPAP for moderate respiratory difficulties, to
further inform future clinical studies.
PMID- 28700566
TI - Enhancing pediatric clinical trial feasibility through the use of Bayesian
statistics.
AB - BackgroundPediatric clinical trials commonly experience recruitment challenges
including limited number of patients and investigators, inclusion/exclusion
criteria that further reduce the patient pool, and a competitive research
landscape created by pediatric regulatory commitments. To overcome these
challenges, innovative approaches are needed.MethodsThis article explores the use
of Bayesian statistics to improve pediatric trial feasibility, using pediatric
Type-2 diabetes as an example. Data for six therapies approved for adults were
used to perform simulations to determine the impact on pediatric trial
size.ResultsWhen the number of adult patients contributing to the simulation was
assumed to be the same as the number of patients to be enrolled in the pediatric
trial, the pediatric trial size was reduced by 75-78% when compared with a
frequentist statistical approach, but was associated with a 34-45% false-positive
rate. In subsequent simulations, greater control was exerted over the false
positive rate by decreasing the contribution of the adult data. A 30-33%
reduction in trial size was achieved when false-positives were held to less than
10%.ConclusionReducing the trial size through the use of Bayesian statistics
would facilitate completion of pediatric trials, enabling drugs to be labeled
appropriately for children.
PMID- 28700567
TI - Recombinant CCN1 prevents hyperoxia-induced lung injury in neonatal rats.
AB - BackgroundCystein-rich protein 61 (Cyr61/CCN1) is a member of the CCN family of
matricellular proteins that has an important role in tissue development and
remodeling. However, the role of CCN1 in the pathogenesis of bronchopulmonary
dysplasia (BPD) is unknown. Accordingly, we have investigated the effects of CCN1
on a hyperoxia-induced lung injury model in neonatal rats.MethodsIn experiment 1,
newborn rats were randomized to room air (RA) or 85% oxygen (O2) for 7 or 14
days, and we assessed the expression of CCN1. In experiment 2, rat pups were
exposed to RA or O2 and received placebo or recombinant CCN1 by daily
intraperitoneal injection for 10 days. The effects of CCN1 on hyperoxia-induced
lung inflammation, alveolar and vascular development, vascular remodeling, and
right ventricular hypertrophy (RVH) were observed.ResultsIn experiment 1,
hyperoxia downregulated CCN1 expression. In experiment 2, treatment with
recombinant CCN1 significantly decreased macrophage and neutrophil infiltration,
reduced inflammasome activation, increased alveolar and vascular development, and
reduced vascular remodeling and RVH in the hyperoxic animals.ConclusionThese
results demonstrate that hyperoxia-induced lung injury is associated with
downregulated basal CCN1 expression, and treatment with CCN1 can largely reverse
hyperoxic injury.
PMID- 28700568
TI - Neonatal basal ganglia and thalamic volumes: very preterm birth and 7-year
neurodevelopmental outcomes.
AB - BackgroundThis study aims to (i) compare volumes of individual basal ganglia
nuclei (caudate nucleus, pallidum, and putamen) and the thalamus between very
preterm (VP) and term-born infants at term-equivalent age; (ii) explore neonatal
basal ganglia and thalamic volume relationships with 7-year neurodevelopmental
outcomes, and whether these relationships differed between VP and term-born
children.Methods210 VP (<30 weeks' gestational age) and 39 term-born (>=37 weeks'
gestational age) infants underwent brain magnetic resonance imaging at term
equivalent age, and deep gray matter volumes of interest were automatically
generated. 186 VP and 37 term-born children were assessed for a range of
neurodevelopmental measures at age 7 years.ResultsAll deep gray matter structures
examined were smaller in VP infants compared with controls at term-equivalent
age; ranging from (percentage mean difference (95% confidence intervals) -6.2% (
10.2%, -2.2%) for the putamen, to -9.5% (-13.9%, -5.1%) for the caudate nucleus.
Neonatal basal ganglia and thalamic volumes were positively related to motor,
intelligence quotient, and academic outcomes at age 7 years, with mostly similar
relationships in the VP and control groups.ConclusionVP birth results in smaller
basal ganglia and thalamic volumes at term-equivalent age, and these smaller
volumes are related to a range of 7-year neurodevelopmental deficits in VP
children.
PMID- 28700569
TI - Pediatric use of tetracyclines: focus on neurodevelopmental effects.
PMID- 28700570
TI - Environmental health reform in a synthetic world.
PMID- 28700571
TI - Open and closed structures reveal allostery and pliability in the HIV-1 envelope
spike.
AB - For many enveloped viruses, binding to a receptor(s) on a host cell acts as the
first step in a series of events culminating in fusion with the host cell
membrane and transfer of genetic material for replication. The envelope
glycoprotein (Env) trimer on the surface of HIV is responsible for receptor
binding and fusion. Although Env can tolerate a high degree of mutation in five
variable regions (V1-V5), and also at N-linked glycosylation sites that
contribute roughly half the mass of Env, the functional sites for recognition of
receptor CD4 and co-receptor CXCR4/CCR5 are conserved and essential for viral
fitness. Soluble SOSIP Env trimers are structural and antigenic mimics of the pre
fusion native, surface-presented Env, and are targets of broadly neutralizing
antibodies. Thus, they are attractive immunogens for vaccine development. Here we
present high-resolution cryo-electron microscopy structures of subtype B B41
SOSIP Env trimers in complex with CD4 and antibody 17b, or with antibody b12, at
resolutions of 3.7 A and 3.6 A, respectively. We compare these to cryo-electron
microscopy reconstructions of B41 SOSIP Env trimers with no ligand or in complex
with either CD4 or the CD4-binding-site antibody PGV04 at 5.6 A, 5.2 A and 7.4 A
resolution, respectively. Consequently, we present the most complete description
yet, to our knowledge, of the CD4-17b-induced intermediate and provide the
molecular basis of the receptor-binding-induced conformational change required
for HIV-1 entry into host cells. Both CD4 and b12 induce large, previously
uncharacterized conformational rearrangements in the gp41 subunits, and the
fusion peptide becomes buried in a newly formed pocket. These structures provide
key details on the biological function of the type I viral fusion machine from
HIV-1 as well as new templates for inhibitor design.
PMID- 28700572
TI - Biomechanics: How fish feel the flow.
PMID- 28700573
TI - CRISPR-Cas encoding of a digital movie into the genomes of a population of living
bacteria.
AB - DNA is an excellent medium for archiving data. Recent efforts have illustrated
the potential for information storage in DNA using synthesized oligonucleotides
assembled in vitro. A relatively unexplored avenue of information storage in DNA
is the ability to write information into the genome of a living cell by the
addition of nucleotides over time. Using the Cas1-Cas2 integrase, the CRISPR-Cas
microbial immune system stores the nucleotide content of invading viruses to
confer adaptive immunity. When harnessed, this system has the potential to write
arbitrary information into the genome. Here we use the CRISPR-Cas system to
encode the pixel values of black and white images and a short movie into the
genomes of a population of living bacteria. In doing so, we push the technical
limits of this information storage system and optimize strategies to minimize
those limitations. We also uncover underlying principles of the CRISPR-Cas
adaptation system, including sequence determinants of spacer acquisition that are
relevant for understanding both the basic biology of bacterial adaptation and its
technological applications. This work demonstrates that this system can capture
and stably store practical amounts of real data within the genomes of populations
of living cells.
PMID- 28700574
TI - Corrigendum: Molecular mechanism for the regulation of yeast separase by securin.
AB - This corrects the article DOI: 10.1038/nature21061.
PMID- 28700575
TI - Synaptic organization of visual space in primary visual cortex.
AB - How a sensory stimulus is processed and perceived depends on the surrounding
sensory scene. In the visual cortex, contextual signals can be conveyed by an
extensive network of intra- and inter-areal excitatory connections that link
neurons representing stimulus features separated in visual space. However, the
connectional logic of visual contextual inputs remains unknown; it is not clear
what information individual neurons receive from different parts of the visual
field, nor how this input relates to the visual features that a neuron encodes,
defined by its spatial receptive field. Here we determine the organization of
excitatory synaptic inputs responding to different locations in the visual scene
by mapping spatial receptive fields in dendritic spines of mouse visual cortex
neurons using two-photon calcium imaging. We find that neurons receive
functionally diverse inputs from extended regions of visual space. Inputs
representing similar visual features from the same location in visual space are
more likely to cluster on neighbouring spines. Inputs from visual field regions
beyond the receptive field of the postsynaptic neuron often synapse on higher
order dendritic branches. These putative long-range inputs are more frequent and
more likely to share the preference for oriented edges with the postsynaptic
neuron when the receptive field of the input is spatially displaced along the
axis of the receptive field orientation of the postsynaptic neuron. Therefore,
the connectivity between neurons with displaced receptive fields obeys a specific
rule, whereby they connect preferentially when their receptive fields are co
oriented and co-axially aligned. This organization of synaptic connectivity is
ideally suited for the amplification of elongated edges, which are enriched in
the visual environment, and thus provides a potential substrate for contour
integration and object grouping.
PMID- 28700576
TI - Cholangiocytes act as facultative liver stem cells during impaired hepatocyte
regeneration.
AB - After liver injury, regeneration occurs through self-replication of hepatocytes.
In severe liver injury, hepatocyte proliferation is impaired-a feature of human
chronic liver disease. It is unclear whether other liver cell types can
regenerate hepatocytes. Here we use two independent systems to impair hepatocyte
proliferation during liver injury to evaluate the contribution of non-hepatocytes
to parenchymal regeneration. First, loss of beta1-integrin in hepatocytes with
liver injury triggered a ductular reaction of cholangiocyte origin, with
approximately 25% of hepatocytes being derived from a non-hepatocyte origin.
Second, cholangiocytes were lineage traced with concurrent inhibition of
hepatocyte proliferation by beta1-integrin knockdown or p21 overexpression,
resulting in the significant emergence of cholangiocyte-derived hepatocytes. We
describe a model of combined liver injury and inhibition of hepatocyte
proliferation that causes physiologically significant levels of regeneration of
functional hepatocytes from biliary cells.
PMID- 28700577
TI - Corrigendum: Splicing factor 1 modulates dietary restriction and TORC1 pathway
longevity in C. elegans.
AB - This corrects the article DOI: 10.1038/nature20789.
PMID- 28700578
TI - A novel mechanism for mechanosensory-based rheotaxis in larval zebrafish.
AB - When flying or swimming, animals must adjust their own movement to compensate for
displacements induced by the flow of the surrounding air or water. These flow
induced displacements can most easily be detected as visual whole-field motion
with respect to the animal's frame of reference. Despite this, many aquatic
animals consistently orient and swim against oncoming flows (a behaviour known as
rheotaxis) even in the absence of visual cues. How animals achieve this task, and
its underlying sensory basis, is still unknown. Here we show that, in the absence
of visual information, larval zebrafish (Danio rerio) perform rheotaxis by using
flow velocity gradients as navigational cues. We present behavioural data that
support a novel algorithm based on such local velocity gradients that fish use to
avoid getting dragged by flowing water. Specifically, we show that fish use their
mechanosensory lateral line to first sense the curl (or vorticity) of the local
velocity vector field to detect the presence of flow and, second, to measure its
temporal change after swim bouts to deduce flow direction. These results reveal
an elegant navigational strategy based on the sensing of flow velocity gradients
and provide a comprehensive behavioural algorithm, also applicable for robotic
design, that generalizes to a wide range of animal behaviours in moving fluids.
PMID- 28700579
TI - TFH-derived dopamine accelerates productive synapses in germinal centres.
AB - Protective high-affinity antibody responses depend on competitive selection of B
cells carrying somatically mutated B-cell receptors by follicular helper T (TFH)
cells in germinal centres. The rapid T-B-cell interactions that occur during this
process are reminiscent of neural synaptic transmission pathways. Here we show
that a proportion of human TFH cells contain dense-core granules marked by
chromogranin B, which are normally found in neuronal presynaptic terminals
storing catecholamines such as dopamine. TFH cells produce high amounts of
dopamine and release it upon cognate interaction with B cells. Dopamine causes
rapid translocation of intracellular ICOSL (inducible T-cell co-stimulator
ligand, also known as ICOSLG) to the B-cell surface, which enhances accumulation
of CD40L and chromogranin B granules at the human TFH cell synapse and increases
the synapse area. Mathematical modelling suggests that faster dopamine-induced T
B-cell interactions increase total germinal centre output and accelerate it by
days. Delivery of neurotransmitters across the T-B-cell synapse may be
advantageous in the face of infection.
PMID- 28700580
TI - Infant viewing of social scenes is under genetic control and is atypical in
autism.
AB - Long before infants reach, crawl or walk, they explore the world by looking: they
look to learn and to engage, giving preferential attention to social stimuli,
including faces, face-like stimuli and biological motion. This capacity-social
visual engagement-shapes typical infant development from birth and is
pathognomonically impaired in children affected by autism. Here we show that
variation in viewing of social scenes, including levels of preferential attention
and the timing, direction and targeting of individual eye movements, is strongly
influenced by genetic factors, with effects directly traceable to the active
seeking of social information. In a series of eye-tracking experiments conducted
with 338 toddlers, including 166 epidemiologically ascertained twins (enrolled by
representative sampling from the general population), 88 non-twins with autism
and 84 singleton controls, we find high monozygotic twin-twin concordance (0.91)
and relatively low dizygotic concordance (0.35). Moreover, the characteristics
that are the most highly heritable, preferential attention to eye and mouth
regions of the face, are also those that are differentially decreased in children
with autism (chi2 = 64.03, P < 0.0001). These results implicate social visual
engagement as a neurodevelopmental endophenotype not only for autism, but also
for population-wide variation in social-information seeking. In addition, these
results reveal a means of human biological niche construction, with phenotypic
differences emerging from the interaction of individual genotypes with early life
experience.
PMID- 28700581
TI - Corrigendum: Crystal structure of the GLP-1 receptor bound to a peptide agonist.
AB - This corrects the article DOI: 10.1038/nature22800.
PMID- 28700582
TI - Neurobiology: Synapses get together for vision.
PMID- 28700583
TI - Immunology: Nervous crosstalk to make antibodies.
PMID- 28700584
TI - The selfish germ.
AB - Curiosity about the sex life of a wasp led to a new way of thinking and a
powerful demonstration that evolutionary science could be predictive. That same
approach could help find ways to slow or prevent treatment failures in cancer and
infectious diseases.
PMID- 28700585
TI - Validation of the sensitivity of the National Emergency X-Radiography Utilization
Study (NEXUS) Head computed tomographic (CT) decision instrument for selective
imaging of blunt head injury patients: An observational study.
AB - BACKGROUND: Clinicians, afraid of missing intracranial injuries, liberally obtain
computed tomographic (CT) head imaging in blunt trauma patients. Prior work
suggests that clinical criteria (National Emergency X-Radiography Utilization
Study [NEXUS] Head CT decision instrument [DI]) can reliably identify patients
with important injuries, while excluding injury, and the need for imaging in many
patients. Validating this DI requires confirmation of the hypothesis that the
lower 95% confidence limit for its sensitivity in detecting serious injury
exceeds 99.0%. A secondary goal of the study was to complete an independent
validation and comparison of the Canadian and NEXUS Head CT rules among the
subgroup of patients meeting the inclusion and exclusion criteria. METHODS AND
FINDINGS: We conducted a prospective observational study of the NEXUS Head CT DI
in 4 hospital emergency departments between April 2006 and December 2015.
Implementation of the rule requires that patients satisfy 8 criteria to achieve
"low-risk" classification. Patients are excluded from "low-risk" classification
and assigned "high-risk" status if they fail to meet 1 or more criteria. We
examined the instrument's performance in assigning "high-risk" status to patients
requiring neurosurgical intervention among a cohort of 11,770 blunt head injury
patients. The NEXUS Head CT DI assigned high-risk status to 420 of 420 patients
requiring neurosurgical intervention (sensitivity, 100.0% [95% confidence
interval [CI]: 99.1%-100.0%]). The instrument assigned low-risk status to 2,823
of 11,350 patients who did not require neurosurgical intervention (specificity,
24.9% [95% CI: 24.1%-25.7%]). None of the 2,823 low-risk patients required
neurosurgical intervention (negative predictive value [NPV], 100.0% [95% CI:
99.9%-100.0%]). The DI assigned high-risk status to 759 of 767 patients with
significant intracranial injuries (sensitivity, 99.0% [95% CI: 98.0%-99.6%]). The
instrument assigned low-risk status to 2,815 of 11,003 patients who did not have
significant injuries (specificity, 25.6% [95% CI: 24.8%-26.4%]). Significant
injuries were absent in 2,815 of the 2,823 patients assigned low-risk status
(NPV, 99.7% [95% CI: 99.4%-99.9%]). Of our patients, 7,759 (65.9%) met the
inclusion and exclusion criteria of the Canadian Head CT rule, including 111
patients (1.43%) who required neurosurgical intervention and 306 (3.94%) who had
significant intracranial injuries. In our study, the Canadian criteria for
neurosurgical intervention identified 108 of 111 patients requiring neurosurgical
intervention to yield a sensitivity of 97.3% (95% CI: 92.3%-99.4%) and exhibited
a specificity of 58.8% (95% CI: 57.7%-59.9%). The NEXUS rule, when applied to
this same cohort, identified all 111 patients requiring neurosurgical
intervention, yielding a sensitivity of 100% (95% CI: 96.7%-100.0%) with a
specificity of 32.6% (95% CI: 31.5%-33.6%). Our study found that the Canadian
medium-risk factors identified 301 of 306 patients with significant injuries
(sensitivity = 98.4%; 95% CI: 96.2%-99.5%), while the NEXUS rule identified 299
of these patients (sensitivity = 97.7%; 95% CI: 95.3%-99.1%). In our study, the
Canadian medium-risk rule exhibited a specificity of 12.3% (95% CI: 11.6%-13.1%),
while the NEXUS rule exhibited a specificity of 33.3% (95% CI: 32.3%-34.4%).
Limitations of the study may arise from application of the rule by different
clinicians in different environments. Clinicians may vary in their interpretation
and application of the instrument's criteria and risk assignment and may also
vary in deciding which patients require intervention. The instrument's
specificity is also subject to spectrum bias and may change with variations in
the proportion of "low-risk" patients seen in other centers. CONCLUSIONS: The
NEXUS Head CT DI reliably identifies blunt trauma patients who require head CT
imaging and could significantly reduce the use of CT imaging.
PMID- 28700586
TI - Systematic identification and characterization of regulatory elements derived
from human endogenous retroviruses.
AB - Human endogenous retroviruses (HERVs) and other long terminal repeat (LTR)-type
retrotransposons (HERV/LTRs) have regulatory elements that possibly influence the
transcription of host genes. We systematically identified and characterized these
regulatory elements based on publicly available datasets of ChIP-Seq of 97
transcription factors (TFs) provided by ENCODE and Roadmap Epigenomics projects.
We determined transcription factor-binding sites (TFBSs) using the ChIP-Seq
datasets and identified TFBSs observed on HERV/LTR sequences (HERV-TFBSs).
Overall, 794,972 HERV-TFBSs were identified. Subsequently, we identified
"HERV/LTR-shared regulatory element (HSRE)," defined as a TF-binding motif in
HERV-TFBSs, shared within a substantial fraction of a HERV/LTR type. HSREs could
be an indication that the regulatory elements of HERV/LTRs are present before
their insertions. We identified 2,201 HSREs, comprising specific associations of
354 HERV/LTRs and 84 TFs. Clustering analysis showed that HERV/LTRs can be
grouped according to the TF binding patterns; HERV/LTR groups bounded to
pluripotent TFs (e.g., SOX2, POU5F1, and NANOG), embryonic endoderm/mesendoderm
TFs (e.g., GATA4/6, SOX17, and FOXA1/2), hematopoietic TFs (e.g., SPI1 (PU1),
GATA1/2, and TAL1), and CTCF were identified. Regulatory elements of HERV/LTRs
tended to locate nearby and/or interact three-dimensionally with the genes
involved in immune responses, indicating that the regulatory elements play an
important role in controlling the immune regulatory network. Further, we
demonstrated subgroup-specific TF binding within LTR7, LTR5B, and LTR5_Hs,
indicating that gains or losses of the regulatory elements occurred during
genomic invasions of the HERV/LTRs. Finally, we constructed dbHERV-REs, an
interactive database of HERV/LTR regulatory elements (http://herv-tfbs.com/).
This study provides fundamental information in understanding the impact of
HERV/LTRs on host transcription, and offers insights into the transcriptional
modulation systems of HERV/LTRs and ancestral HERVs.
PMID- 28700587
TI - Community and health system intervention to reduce disrespect and abuse during
childbirth in Tanga Region, Tanzania: A comparative before-and-after study.
AB - BACKGROUND: Abusive treatment of women during childbirth has been documented in
low-resource countries and is a deterrent to facility utilization for delivery.
Evidence for interventions to address women's poor experience is scant. We
assessed a participatory community and health system intervention to reduce the
prevalence of disrespect and abuse during childbirth in Tanzania. METHODS AND
FINDINGS: We used a comparative before-and-after evaluation design to test the
combined intervention to reduce disrespect and abuse. Two hospitals in Tanga
Region, Tanzania were included in the study, 1 randomly assigned to receive the
intervention. Women who delivered at the study facilities were eligible to
participate and were recruited upon discharge. Surveys were conducted at baseline
(December 2011 through May 2012) and after the intervention (March through
September 2015). The intervention consisted of a client service charter and a
facility-based, quality-improvement process aimed to redefine norms and practices
for respectful maternity care. The primary outcome was any self-reported
experiences of disrespect and abuse during childbirth. We used multivariable
logistic regression to estimate a difference-in-difference model. At baseline,
2,085 women at the 2 study hospitals who had been discharged from the maternity
ward after delivery were invited to participate in the survey. Of these, 1,388
(66.57%) agreed to participate. At endline, 1,680 women participated in the
survey (72.29% of those approached). The intervention was associated with a 66%
reduced odds of a woman experiencing disrespect and abuse during childbirth (odds
ratio [OR]: 0.34, 95% CI: 0.21-0.58, p < 0.0001). The biggest reductions were for
physical abuse (OR: 0.22, 95% CI: 0.05-0.97, p = 0.045) and neglect (OR: 0.36,
95% CI: 0.19-0.71, p = 0.003). The study involved only 2 hospitals in Tanzania
and is thus a proof-of-concept study. Future, larger-scale research should be
undertaken to evaluate the applicability of this approach to other settings.
CONCLUSIONS: After implementation of the combined intervention, the likelihood of
women's reports of disrespectful treatment during childbirth was substantially
reduced. These results were observed nearly 1 year after the end of the project's
facilitation of implementation, indicating the potential for sustainability. The
results indicate that a participatory community and health system intervention
designed to tackle disrespect and abuse by changing the norms and standards of
care is a potential strategy to improve the treatment of women during childbirth
at health facilities. The trial is registered on the ISRCTN Registry, ISRCTN
48258486. TRIAL REGISTRATION: ISRCTN Registry, ISRCTN 48258486.
PMID- 28700588
TI - Years of life lost due to traumatic brain injury in Europe: A cross-sectional
analysis of 16 countries.
AB - INTRODUCTION: Traumatic brain injuries (TBIs) are a major public health, medical,
and societal challenge globally. They present a substantial burden to victims,
their families, and the society as a whole. Although indicators such as incidence
or death rates provide insight into the occurrence and outcome of TBIs in various
populations, they fail to quantify the full extent of their public health and
societal impact. Measures such as years of life lost (YLLs), which quantifies the
number of years of life lost because the person dies prematurely due to a disease
or injury, should be employed to better quantify the population impact. The aim
of this study was to provide an in-depth analysis of the burden of deaths due to
TBI by calculating TBI-specific YLLs in 16 European countries, analyzing their
main causes and demographic patterns, using data extracted from death
certificates under unified guidelines and collected in a standardized manner.
METHODS AND FINDINGS: A population-wide, cross-sectional epidemiological study
was conducted in 16 European countries to estimate TBI YLLs for the year 2013.
The data used for all analyses in this study were acquired from the statistical
office of the European Union (Eurostat). A specifically tailored dataset of micro
level data was provided that listed the external cause of death (International
Classification of Diseases-10th Revision [ICD-10] codes V01-Y98), the specific
nature of injury (ICD-10 codes S00-T98), the age at death, and sex for each
death. Overall number of TBI YLLs, crude and age-standardized TBI YLL rates, and
TBI YLLs per case were calculated stratified for country, sex, and age. Pooled
analyses were performed in order to estimate summary age-standardized rates of
TBI YLLs. In order to evaluate the relative importance of TBI in the context of
all injuries, proportions of TBI YLLs out of overall injury YLLs were calculated.
The total number of TBI YLLs was estimated by extrapolating the pooled crude rate
of TBI YLLs in the 16 analyzed countries to the total population of the 28 member
states of the EU (EU-28). We found that a total of 17,049 TBI deaths occurred in
2013 in the 16 analyzed countries. These translated into a total of 374,636 YLLs.
The pooled age-standardized rate of YLLs per 100,000 people per year was 259.1
(95% CI: 205.8 to 312.3) overall, 427.5 (95% CI: 290.0 to 564.9) in males, and
105.4 (95% CI: 89.1 to 121.6) in females. Males contributed substantially more to
TBI YLLs than females (282,870 YLLs, 76% of all TBI YLLs), which translated into
a rate ratio of 3.24 (95% CI: 3.22 to 3.27). Each TBI death was on average
associated with 24.3 (95% CI: 22.0 to 26.6) YLLs overall, 25.6 (95% CI: 23.4 to
27.8) in males and 20.9 (17.9 to 24.0) in females. Falls and traffic crashes were
the most common external causes of TBI YLLs. TBI contributed on average 41% (44%
in males and 34% in females) to overall injury YLLs. Extrapolating our findings,
about 1.3 million YLLs were attributable to TBI in the EU-28 in 2013 overall, 1.1
million in males and 271,000 in females. This study is based on administratively
collected data from 16 countries, and despite the efforts to harmonize them to
the greatest possible extent, there may be differences in coding practices or
reporting between countries. If present, these would be inherited into our
findings without our ability to control for them. The extrapolation of the pooled
rates from the 16 countries to the EU-28 should be interpreted with caution.
CONCLUSIONS: Our study showed that TBI-related deaths and YLLs have a substantial
impact at the individual and population level in Europe and present an important
societal and economic burden that must not be overlooked. We provide information
valuable for policy-makers, enabling them to evaluate and plan preventive
activities and resource allocation, and to formulate and implement strategic
decisions. In addition, our results can serve as a basis for analyzing the
overall burden of TBI in the population.
PMID- 28700589
TI - ANK1 is up-regulated in laser captured microglia in Alzheimer's brain; the
importance of addressing cellular heterogeneity.
AB - Recent epigenetic association studies have identified a new gene, ANK1, in the
pathogenesis of Alzheimer's disease (AD). Although strong associations were
observed, brain homogenates were used to generate the data, introducing
complications because of the range of cell types analyzed. In order to address
the issue of cellular heterogeneity in homogenate samples we isolated microglial,
astrocytes and neurons by laser capture microdissection from CA1 of hippocampus
in the same individuals with a clinical and pathological diagnosis of AD and
matched control cases. Using this unique RNAseq data set, we show that in the
hippocampus, ANK1 is significantly (p<0.0001) up-regulated 4-fold in AD
microglia, but not in neurons or astrocytes from the same individuals. These data
provide evidence that microglia are the source of ANK1 differential expression
previously identified in homogenate samples in AD.
PMID- 28700590
TI - Greenhouse gas emissions from dung pats vary with dung beetle species and with
assemblage composition.
AB - Cattle farming is a major source of greenhouse gases (GHGs). Recent research
suggests that GHG fluxes from dung pats could be affected by biotic interactions
involving dung beetles. Whether and how these effects vary among beetle species
and with assemblage composition is yet to be established. To examine the link
between GHGs and different dung beetle species assemblages, we used a closed
chamber system to measure fluxes of carbon dioxide (CO2), methane (CH4) and
nitrous oxide (N2O) from cattle dung pats. Targeting a total of four dung beetle
species (a pat-dwelling species, a roller of dung balls, a large and a small
tunnelling species), we ran six experimental treatments (four monospecific and
two mixed) and two controls (one with dung but without beetles, and one with
neither dung nor beetles). In this setting, the overall presence of beetles
significantly affected the gas fluxes, but different species contributed
unequally to GHG emissions. When compared to the control with dung, we detected
an overall reduction in the total cumulative CO2 flux from all treatments with
beetles and a reduction in N2O flux from the treatments with the three most
abundant dung beetle species. These reductions can be seen as beneficial
ecosystem services. Nonetheless, we also observed a disservice provided by the
large tunneler, Copris lunaris, which significantly increased the CH4 flux-an
effect potentially traceable to the species' nesting strategy involving the
construction of large brood balls. When fluxes were summed into CO2-equivalents
across individual GHG compounds, dung with beetles proved to emit less GHGs than
did beetle-free dung, with the mix of the three most abundant species providing
the highest reduction (-32%). As the mix of multiple species proved the most
effective in reducing CO2-equivalents, the conservation of diverse assemblages of
dung beetles emerges as a priority in agro-pastoral ecosystems.
PMID- 28700591
TI - Trends in traumatic brain injury mortality in China, 2006-2013: A population
based longitudinal study.
AB - BACKGROUND: Traumatic brain injury (TBI) is a significant global public health
problem, but has received minimal attention from researchers and policy-makers in
low- and middle-income countries (LMICs). Epidemiological evidence of TBI
morbidity and mortality is absent at the national level for most LMICs, including
China. Using data from China's Disease Surveillance Points (DSPs) system, we
conducted a population-based longitudinal analysis to examine TBI mortality, and
mortality differences by sex, age group, location (urban/rural), and external
cause of injury, from 1 January 2006 to 31 December 2013 in China. METHOD AND
FINDINGS: Mortality data came from the national DSPs system of China, which has
coded deaths using the International Classification of Diseases-10th Revision
(ICD-10) since 2004. Crude and age-standardized mortality with 95% CIs were
estimated using the census population in 2010 as a reference population. The
Cochran-Armitage trend test was used to examine the significance of trends in
mortality from 2006 to 2013. Negative binomial models were used to examine the
associations of TBI mortality with location, sex, and age group. Subgroup
analysis was performed by external cause of TBI. We found the following: (1) Age
adjusted TBI mortality increased from 13.23 per 100,000 population in 2006 to
17.06 per 100,000 population in 2008 and then began to fall slightly. In 2013,
age-adjusted TBI mortality was 12.99 per 100,000 population (SE = 0.13). (2)
Compared to females and urban residents, males and rural residents had higher TBI
mortality risk, with adjusted mortality rate ratios of 2.57 and 1.71,
respectively. TBI mortality increased substantially with older age. (3) Motor
vehicle crashes and falls were the 2 leading causes of TBI mortality between 2006
and 2013. TBI deaths from motor vehicle crashes in children aged 0-14 years and
adults aged 65 years and older were most often in pedestrians, and motorcyclists
were the first or second leading category of road user for the other age groups.
(4) TBI mortality attributed to motor vehicle crashes increased for pedestrians
and motorcyclists in all 7 age groups from 2006 to 2013. Our analysis was limited
by the availability and quality of data in the DSPs dataset, including lack of
injury-related socio-economic factors, policy factors, and individual and
behavioral factors. The dataset also may be incomplete in TBI death recording or
contain misclassification of mortality data. CONCLUSIONS: TBI constitutes a
serious public health threat in China. Further studies should explore the reasons
for the particularly high risk of TBI mortality among particular populations, as
well as the reasons for recent increases in certain subgroups, and should develop
solutions to address these challenges. Interventions proven to work in other
cultures should be introduced and implemented nationwide. Examples of these in
the domain of motor vehicle crashes include policy change and enforcement of laws
concerning helmet use for motorcyclists and bicyclists, car seat and booster seat
use for child motor vehicle passengers, speed limit and drunk driving laws, and
alcohol ignition interlock use. Examples to prevent falls, especially among
elderly individuals, include exercise programs, home modification to reduce fall
risk, and multifaceted interventions to prevent falls in all age groups.
PMID- 28700592
TI - Genome-wide identification of gene expression in contrasting maize inbred lines
under field drought conditions reveals the significance of transcription factors
in drought tolerance.
AB - Drought is a major threat to maize growth and production. Understanding the
molecular regulation network of drought tolerance in maize is of great
importance. In this study, two maize inbred lines with contrasting drought
tolerance were tested in the field under natural soil drought and well-watered
conditions. In addition, the transcriptomes of their leaves was analyzed by RNA
Seq. In total, 555 and 2,558 genes were detected to specifically respond to
drought in the tolerant and the sensitive line, respectively, with a more
positive regulation tendency in the tolerant genotype. Furthermore, 4,700, 4,748,
4,403 and 4,288 genes showed differential expression between the two lines under
moderate drought, severe drought and their well-watered controls, respectively.
Transcription factors were enriched in both genotypic differentially expressed
genes and specifically responsive genes of the tolerant line. It was speculated
that the genotype-specific response of 20 transcription factors in the tolerance
line and the sustained genotypically differential expression of 22 transcription
factors might enhance tolerance to drought in maize. Our results provide new
insight into maize drought tolerance-related regulation systems and provide gene
resources for subsequent studies and drought tolerance improvement.
PMID- 28700593
TI - Implementation of a loss-of-function system to determine growth and stress
associated mutagenesis in Bacillus subtilis.
AB - A forward mutagenesis system based on the acquisition of mutations that
inactivate the thymidylate synthase gene (TMS) and confer a trimethoprim
resistant (Tmpr) phenotype was developed and utilized to study transcription
mediated mutagenesis (TMM). In addition to thyA, Bacillus subtilis possesses
thyB, whose expression occurs under conditions of cell stress; therefore, we
generated a thyB- thyA+ mutant strain. Tmpr colonies of this strain were produced
with a spontaneous mutation frequency of ~1.4 * 10-9. Genetic disruption of the
canonical mismatch (MMR) and guanine oxidized (GO) repair pathways increased the
Tmpr frequency of mutation by ~2-3 orders of magnitude. A wide spectrum of base
substitutions as well as insertion and deletions in the ORF of thyA were found to
confer a Tmpr phenotype. Stationary-phase-associated mutagenesis (SPM) assays
revealed that colonies with a Tmpr phenotype, accumulated over a period of ten
days with a frequency of ~ 60 *10-7. The Tmpr system was further modified to
study TMM by constructing a DeltathyA DeltathyB strain carrying an IPTG-inducible
Pspac-thyA cassette. In conditions of transcriptional induction of thyA, the
generation of Tmpr colonies increased ~3-fold compared to conditions of
transcriptional repression. Further, the Mfd and GreA factors were necessary for
the generation of Tmpr colonies in the presence of IPTG in B. subtilis. Because
GreA and Mfd facilitate transcription-coupled repair, our results suggest that
TMM is a mechanim to produce genetic diversity in highly transcribed regions in
growth-limited B. subtilis cells.
PMID- 28700594
TI - Hierarchical patterning modes orchestrate hair follicle morphogenesis.
AB - Two theories address the origin of repeating patterns, such as hair follicles,
limb digits, and intestinal villi, during development. The Turing reaction
diffusion system posits that interacting diffusible signals produced by static
cells first define a prepattern that then induces cell rearrangements to produce
an anatomical structure. The second theory, that of mesenchymal self
organisation, proposes that mobile cells can form periodic patterns of cell
aggregates directly, without reference to any prepattern. Early hair follicle
development is characterised by the rapid appearance of periodic arrangements of
altered gene expression in the epidermis and prominent clustering of the adjacent
dermal mesenchymal cells. We assess the contributions and interplay between
reaction-diffusion and mesenchymal self-organisation processes in hair follicle
patterning, identifying a network of fibroblast growth factor (FGF), wingless
related integration site (WNT), and bone morphogenetic protein (BMP) signalling
interactions capable of spontaneously producing a periodic pattern. Using time
lapse imaging, we find that mesenchymal cell condensation at hair follicles is
locally directed by an epidermal prepattern. However, imposing this prepattern's
condition of high FGF and low BMP activity across the entire skin reveals a
latent dermal capacity to undergo spatially patterned self-organisation in the
absence of epithelial direction. This mesenchymal self-organisation relies on
restricted transforming growth factor (TGF) beta signalling, which serves to
drive chemotactic mesenchymal patterning when reaction-diffusion patterning is
suppressed, but, in normal conditions, facilitates cell movement to locally
prepatterned sources of FGF. This work illustrates a hierarchy of periodic
patterning modes operating in organogenesis.
PMID- 28700595
TI - Origin of mounds in the Pantanal wetlands: An integrated approach between
geomorphology, pedogenesis, ecology and soil micromorphology.
AB - Vegetated mounds are an important geomorphological feature of the Pantanal, where
the influence of floods dictates not only hydropedological processes, but also
the distribution and ecology of the flora and fauna. This work aimed to identify
factors and processes that influence the formation and spatial distribution of
the mounds, which are commonly associated with termite activity. In order to
characterize pedological processes, macro and micro morphological descriptions,
satellite image interpretation, dating of the sandy sedimentary material using
OSL and carbon dating using 14C AMS were carried out. This dating of the
materials indicates that the sediments in which the soils were formed were
deposited during the Pleistocene, while the carbonates are from the Holocene. The
basin-like format of the laminar structures suggests that part of the more clayey
material was deposited in lacustrine environments. The more humid climate in the
Holocene intensified argilluviation, which at an advanced stage, led to a more
pronounced textural gradient, reducing drainage and leading to ferrolysis and
thickening of the E horizon. Besides pedogenic processes, more erosive flooding
during the Holocene began reducing and rounding the landscape's more elevated
structures (paleolevees). In the final stage, these structures were occupied by
termites to shelter from flooding. Thereafter, the bio-cementation action of the
termite nests has increased the resistance of the vegetated mounds to processes
of erosion.
PMID- 28700596
TI - Methods to estimate underlying blood pressure: The Atherosclerosis Risk in
Communities (ARIC) Study.
AB - Antihypertensive medications complicate studies of blood pressure (BP) natural
history; BP if untreated ("underlying BP") needs to be estimated. Our objectives
were to compare validity of five missing data imputation methods to estimate
underlying BP and longitudinal associations of underlying BP and age. We
simulated BP treatment in untreated hypertensive participants from
Atherosclerosis Risk in Communities (ARIC) in visits 1-5 (1987-2013) using
matched treated hypertensive participants. The underlying BP was imputed: #1, set
as missing; #2, add 10 mmHg for systolic, 5 mmHg for diastolic; #3, add
medication class-specific constant; #4, truncated normal regression; and #5,
truncated normal regression including prior visit data. Longitudinal associations
were estimated using linear mixed models of imputed underlying BP for simulated
treated and measured BP for untreated participants. Method 3 was the best
performing for systolic BP; lowest relative bias (5.3% for intercept at age 50,
0% for age coefficient) and average deviation from expected (0.04 to -1.79).
Method 2 performed best for diastolic BP; lowest relative bias (0.6% intercept at
age 50, 33.3% age <60, 9.1% age 60+) and average deviation (-1.25 to -1.68).
Methods 4 and 5 were comparable or slightly inferior. In conclusion, constant
addition methods yielded valid and precise underlying BP and longitudinal
associations.
PMID- 28700597
TI - Differentially expressed microRNAs in diapausing versus HCl-treated Bombyx
embryos.
AB - Differentially expressed microRNAs were detected to explore the molecular
mechanisms of diapause termination. The total small RNA of diapause-destined
silkworm eggs and HCl-treated eggs was extracted and then sequenced using HiSeq
high-throughput method. 44 novel miRNAs were discovered. Compared to those in the
diapause-destined eggs, 61 miRNAs showed significant changes in the acid-treated
eggs, with 23 being up-regulated and 38 being down-regulated. The potential
target genes of differentially expressed miRNAs were predicted by miRanda. Gene
Ontology and KEGG pathway enrichment analysis of these potential target genes
revealed that they were mainly located within cells and organelles, involved in
cellular and metabolic processes, and participated in protein production,
processing and transportation. Two differentially expressed genes, Bombyx mori
SDH and Bmo-miR-2761-3p, were further analyzed with qRT-PCR. BmSDH was
significantly up-regulated in the HCl-treated eggs, while Bmo-miR-2761-3p was
down-regulated. These results suggested that these two genes were well
coordinated in silkworm eggs. Dual luciferase reporter assay demonstrated that
Bmo-miR-2761-3p inhibited the expression of BmSDH.
PMID- 28700598
TI - Tracing social interactions in Pleistocene North America via 3D model analysis of
stone tool asymmetry.
AB - Stone tools, often the sole remnant of prehistoric hunter-gatherer behavior, are
frequently used as evidence of ancient human mobility, resource use, and
environmental adaptation. In North America, studies of morphological variation in
projectile points have provided important insights into migration and
interactions of human groups as early as 12-13 kya. Using new approaches to 3D
imaging and morphometric analysis, we here quantify bifacial asymmetry among
early North American projectile point styles to better understand changes in
knapping technique and cultural transmission. Using a sample of 100 fluted
bifaces of Clovis and post-Clovis styles in the eastern United States ca. 13,100
9,000 cal BP (i.e., Clovis, Debert-Vail, Bull Brook, Michaud-Neponset/Barnes, and
Crowfield), we employed two different approaches for statistical shape analysis:
our previously presented method for analysis of 2D flake scar contours, and a new
approach for 3D surface analysis using spherical harmonics (SPHARM). Whereas
bifacial asymmetry in point shape does not vary significantly across this
stylistic sequence, our measure of asymmetric flake scar patterning shows
temporal variation that may signify the beginning of regionalization among early
New World colonists.
PMID- 28700599
TI - The prognostic and clinicopathologic characteristics of CD147 and esophagus
cancer: A meta-analysis.
AB - OBJECTIVE: The prognostic significance of CD147 expression in esophageal cancer
patients remains controversial. Using a meta-analysis, we investigated the
prognostic and clinicopathologic characteristics of CD147 in esophageal cancer.
METHODS: A comprehensive literature search of the PubMed (1966-2016), EMBASE
(1980-2016), Cochrane Library (1996-2016), Web of Science (1945-2016), China
National Knowledge Infrastructure (1982-2016), and Wanfang databases (1988-2016)
was performed to identify studies of all esophageal cancer subtypes. Correlations
between CD147 expression and survival outcomes and clinicopathological features
were analyzed using meta-analysis methods. RESULTS: Seventeen studies were
included. High CD147 expression reduced the 3-year survival rate (OR = 3.26, 95%
CI = (1.53, 6.93), p = 0.02) and 5-year survival rate(OR = 4.35, 95% CI = (2.13,
8.90), p < 0.0001). High CD147 expression reduced overall survival in esophageal
cancer (HR = 1.60, 95% CI = (1.19, 2.15), p = 0.02). Additionally, higher CD147
expression was detected in esophageal cancer tissues than noncancerous tissues
(OR = 9.45, 95% CI = (5.39, 16.59), p < 0.00001), normal tissues (OR = 12.73, 95%
CI = (3.49, 46.46), p = 0.0001), para-carcinoma tissues (OR = 12.80, 95% CI =
(6.57, 24.92), p < 0.00001), and hyperplastic tissues (OR = 3.27, 95% CI = (1.47,
7.29), p = 0.004). CD147 expression was associated with TNM stage (OR = 3.66, 95%
CI = (2.20, 6.09), p < 0.00001), tumor depth (OR = 7.97, 95% CI = (4.13, 15.38),
p < 0.00001), and lymph node status (OR = 5.14, 95% CI = (2.03,13.01), p =
0.0005), but not with tumor differentiation, age, or sex. CONCLUSION: Our meta
analysis suggests that CD147 is an efficient prognostic factor in esophageal
cancer. High CD147 expression in patients with esophageal cancer was associated
with worse survival outcomes and common clinicopathological indicators of poor
prognosis.
PMID- 28700600
TI - Ethanol confers differential protection against generalist and specialist
parasitoids of Drosophila melanogaster.
AB - As parasites coevolve with their hosts, they can evolve counter-defenses that
render host immune responses ineffective. These counter-defenses are more likely
to evolve in specialist parasites than generalist parasites; the latter face
variable selection pressures between the different hosts they infect. Natural
populations of the fruit fly Drosophila melanogaster are commonly threatened by
endoparasitoid wasps in the genus Leptopilina, including the specialist L.
boulardi and the generalist L. heterotoma, and both wasp species can incapacitate
the cellular immune response of D. melanogaster larvae. Given that ethanol
tolerance is high in D. melanogaster and stronger in the specialist wasp than the
generalist, we tested whether fly larvae could use ethanol as an anti-parasite
defense and whether its effectiveness would differ against the two wasp species.
We found that fly larvae benefited from eating ethanol-containing food during
exposure to L. heterotoma; we observed a two-fold decrease in parasitization
intensity and a 24-fold increase in fly survival to adulthood. Although host
ethanol consumption did not affect L. boulardi parasitization rates or
intensities, it led to a modest increase in fly survival. Thus, ethanol conferred
stronger protection against the generalist wasp than the specialist. We tested
whether fly larvae can self-medicate by seeking ethanol-containing food after
being attacked by wasps, but found no support for this hypothesis. We also
allowed female flies to choose between control and ethanol-containing oviposition
sites in the presence vs. absence of wasps and generally found significant
preferences for ethanol regardless of wasp presence. Overall, our results suggest
that D. melanogaster larvae obtain protection from certain parasitoid wasp
species through their mothers' innate oviposition preferences for ethanol
containing food sources.
PMID- 28700601
TI - New regression formula to estimate the prenatal crown formation time of human
deciduous central incisors derived from a Roman Imperial sample (Velia, Salerno,
Italy, I-II cent. CE).
AB - The characterization and quantification of human dental enamel microstructure, in
both permanent and deciduous teeth, allows us to document crucial growth
parameters and to identify stressful events, thus contributing to the
reconstruction of the past life history of an individual. Most studies to date
have focused on the more accessible post-natal portion of the deciduous dental
enamel, even though the analysis of prenatal enamel is pivotal in understanding
fetal growth, and reveals information about the mother's health status during
pregnancy. This contribution reports new data describing the prenatal enamel
development of 18 central deciduous incisors from the Imperial Roman necropolis
of Velia (I-II century CE, Salerno, Italy). Histomorphometrical analysis was
performed to collect data on prenatal crown formation times, daily secretion
rates and enamel extension rates. Results for the Velia sample allowed us to
derive a new regression formula, using a robust statistical approach, that
describes the average rates of deciduous enamel formation. This can now be used
as a reference for pre-industrial populations. The same regression formula, even
when daily incremental markings are difficult to visualize, may provide a clue to
predicting the proportion of infants born full term and pre-term in an
archaeological series.
PMID- 28700602
TI - Time for trauma immunology.
AB - Timothy Billiar summarizes the role of the innate immune response in the clinical
course following severe injury and envisions a field of "trauma immunology."
PMID- 28700603
TI - The Language of Glove: Wireless gesture decoder with low-power and stretchable
hybrid electronics.
AB - This communication describes a glove capable of wirelessly translating the
American Sign Language (ASL) alphabet into text displayable on a computer or
smartphone. The key components of the device are strain sensors comprising a
piezoresistive composite of carbon particles embedded in a fluoroelastomer. These
sensors are integrated with a wearable electronic module consisting of
digitizers, a microcontroller, and a Bluetooth radio. Finite-element analysis
predicts a peak strain on the sensors of 5% when the knuckles are fully bent.
Fatigue studies suggest that the sensors successfully detect the articulation of
the knuckles even when bent to their maximal degree 1,000 times. In concert with
an accelerometer and pressure sensors, the glove is able to translate all 26
letters of the ASL alphabet. Lastly, data taken from the glove are used to
control a virtual hand; this application suggests new ways in which stretchable
and wearable electronics can enable humans to interface with virtual
environments. Critically, this system was constructed of components costing less
than $100 and did not require chemical synthesis or access to a cleanroom. It can
thus be used as a test bed for materials scientists to evaluate the performance
of new materials and flexible and stretchable hybrid electronics.
PMID- 28700604
TI - Molecular characterization of the acquisition of longevity during seed maturation
in soybean.
AB - Seed longevity, defined as the ability to remain alive during storage, is an
important agronomic factor. Poor longevity negatively impacts seedling
establishment and consequently crop yield. This is particularly problematic for
soybean as seeds have a short lifespan. While the economic importance of soybean
has fueled a large number of transcriptome studies during embryogenesis and seed
filling, the mechanisms regulating seed longevity during late maturation remain
poorly understood. Here, a detailed physiological and molecular characterization
of late seed maturation was performed in soybean to obtain a comprehensive
overview of the regulatory genes that are potentially involved in longevity.
Longevity appeared at physiological maturity at the end of seed filling before
maturation drying and progressively doubled until the seeds reached the dry
state. The increase in longevity was associated with the expression of genes
encoding protective chaperones such as heat shock proteins and the repression of
nuclear and chloroplast genes involved in a range of chloroplast activities,
including photosynthesis. An increase in the raffinose family oligosaccharides
(RFO)/sucrose ratio together with changes in RFO metabolism genes was also
associated with longevity. A gene co-expression network analysis revealed 27
transcription factors whose expression profiles were highly correlated with
longevity. Eight of them were previously identified in the longevity network of
Medicago truncatula, including homologues of ERF110, HSF6AB, NFXL1 and members of
the DREB2 family. The network also contained several transcription factors
associated with auxin and developmental cell fate during flowering, organ growth
and differentiation. A transcriptional transition occurred concomitant with seed
chlorophyll loss and detachment from the mother plant, suggesting the activation
of a post-abscission program. This transition was enriched with AP2/EREBP and
WRKY transcription factors and genes associated with growth, germination and post
transcriptional processes, suggesting that this program prepares the seed for the
dry quiescent state and germination.
PMID- 28700605
TI - Will farmers intend to cultivate Provitamin A genetically modified (GM) cassava
in Nigeria? Evidence from a k-means segmentation analysis of beliefs and
attitudes.
AB - Analysis of market segments within a population remains critical to agricultural
systems and policy processes for targeting new innovations. Patterns in attitudes
and intentions toward cultivating Provitamin A GM cassava are examined through
the use of a combination of behavioural theory and k-means cluster analysis
method, investigating the interrelationship among various behavioural
antecedents. Using a state-level sample of smallholder cassava farmers in
Nigeria, this paper identifies three distinct classes of attitude and intention
denoted as low opposition, medium opposition and high opposition farmers. It was
estimated that only 25% of the surveyed population of farmers was highly opposed
to cultivating Provitamin A GM cassava.
PMID- 28700606
TI - Cellular therapies in trauma and critical care medicine: Looking towards the
future.
AB - Shibani Pati and Todd Rasmussen summarize progress in preclinical research on
cellular therapeutics for traumatic injury and its sequelae and discuss prospects
for clinical translation.
PMID- 28700607
TI - Life history traits and life table analysis of Lobiopa insularis (Coleoptera:
Nitidulidae) fed on strawberry.
AB - Lobiopa insularis is a newly reported pest of strawberry in Argentina. We
investigated characteristics of its biology in the laboratory, including
survivorship and reproduction. We also estimated population growth for L.
insularis fed ripe strawberry fruits. Lobiopa insularis was not observed
ovipositing on strawberry fruits. A higher proportion of egg masses were recorded
from a depth of 1 cm within the soil than on either the soil surface or deeper
than 1cm (i.e. between 1and 2 cm) within the soil. The duration of preimaginal
developmental stages represented ~18.5% of the total life cycle, while the adult
stage represented 81.5%. Survival from egg to adult was 64.20% and mean longevity
of females and males adults was 121.84, (SE = 8.86) and 118.58 (SE = 5.90) days,
respectively. Females laid eggs only when they were with a male, so reproductive
period was dependent on male presence. The number of eggs/female/day was 18.01
(SE = 1.71); and total fecundity was 1655 (ES = 249.53) eggs/female. The long
life span of adults and high reproductive output, i.e high fecundity and long
reproductive period, indicate that availability and concentration of suitable
developmental resources are important factors in the population dynamics of
Lobiopa insularis associated with strawberry crops.
PMID- 28700608
TI - The ECF sigma factor, PSPTO_1043, in Pseudomonas syringae pv. tomato DC3000 is
induced by oxidative stress and regulates genes involved in oxidative stress
response.
AB - The bacterial plant pathogen Pseudomonas syringae adapts to changes in the
environment by modifying its gene expression profile. In many cases, the response
is mediated by the activation of extracytoplasmic function (ECF) sigma factors
that direct RNA polymerase to transcribe specific sets of genes. In this study we
focus on PSPTO_1043, one of ten ECF sigma factors in P. syringae pv. tomato
DC3000 (DC3000). PSPTO_1043, together with PSPTO_1042, encode an RpoERsp/ChrR
like sigma/anti-sigma factor pair. Although this gene pair is unique to the P.
syringae group among the pseudomonads, homologous genes can be found in
photosynthetic genera such as Rhodospirillum, Thalassospira, Phaeospirillum and
Parvibaculum. Using ChIP-Seq, we detected 137 putative PSPTO_1043 binding sites
and identified a likely promoter motif. We characterized 13 promoter candidates,
six of which regulate genes that appear to be found only in P. syringae.
PSPTO_1043 responds to the presence of singlet oxygen (1O2) and tert-butyl
hydroperoxide (tBOOH) and several of the genes regulated by PSPTO_1043 appear to
be involved in response to oxidative stress.
PMID- 28700609
TI - Organic farming enhances soil microbial abundance and activity-A meta-analysis
and meta-regression.
AB - Population growth and climate change challenge our food and farming systems and
provide arguments for an increased intensification of agriculture. A promising
option is eco-functional intensification through organic farming, an approach
based on using and enhancing internal natural resources and processes to secure
and improve agricultural productivity, while minimizing negative environmental
impacts. In this concept an active soil microbiota plays an important role for
various soil based ecosystem services such as nutrient cycling, erosion control
and pest and disease regulation. Several studies have reported a positive effect
of organic farming on soil health and quality including microbial community
traits. However, so far no systematic quantification of whether organic farming
systems comprise larger and more active soil microbial communities compared to
conventional farming systems was performed on a global scale. Therefore, we
conducted a meta-analysis on current literature to quantify possible differences
in key indicators for soil microbial abundance and activity in organic and
conventional cropping systems. All together we integrated data from 56 mainly
peer-reviewed papers into our analysis, including 149 pairwise comparisons
originating from different climatic zones and experimental duration ranging from
3 to more than 100 years. Overall, we found that organic systems had 32% to 84%
greater microbial biomass carbon, microbial biomass nitrogen, total phospholipid
fatty-acids, and dehydrogenase, urease and protease activities than conventional
systems. Exclusively the metabolic quotient as an indicator for stresses on
microbial communities remained unaffected by the farming systems. Categorical
subgroup analysis revealed that crop rotation, the inclusion of legumes in the
crop rotation and organic inputs are important farming practices affecting soil
microbial community size and activity. Furthermore, we show that differences in
microbial size and activity between organic and conventional farming systems vary
as a function of land use (arable, orchards, and grassland), plant life cycle
(annual and perennial) and climatic zone. In summary, this study shows that
overall organic farming enhances total microbial abundance and activity in
agricultural soils on a global scale.
PMID- 28700610
TI - Perioperative hemodynamics and risk for delirium and new onset dementia in hip
fracture patients; A prospective follow-up study.
AB - BACKGROUND: Delirium is common in hip fracture patients and many risk factors
have been identified. Controversy exists regarding the possible impact of
intraoperative control of blood pressure upon acute (delirium) and long term
(dementia) cognitive decline. We explored possible associations between
perioperative hemodynamic changes, use of vasopressor drugs, risk of delirium and
risk of new-onset dementia. METHODS: Prospective follow-up study of 696 hip
fracture patients, assessed for delirium pre- and postoperatively, using the
Confusion Assessment Method. Pre-fracture cognitive function was assessed using
the Informant Questionnaire of Cognitive Decline in the Elderly and by consensus
diagnosis. The presence of new-onset dementia was determined at follow-up
evaluation at six or twelve months after surgery. Blood pressure was recorded at
admission, perioperatively and postoperatively. RESULTS: Preoperative delirium
was present in 149 of 536 (28%) assessable patients, and 124 of 387 (32%)
developed delirium postoperatively (incident delirium). The following risk
factors for incident delirium in patients without pre-fracture cognitive
impairment were identified: low body mass index, low level of functioning,
severity of physical illness, and receipt of >= 2 blood transfusions. New-onset
dementia was diagnosed at follow-up in 26 of 213 (12%) patients, associated with
severity of physical illness, delirium, receipt of vasopressor drugs
perioperatively and high mean arterial pressure postoperatively. CONCLUSION: Risk
factors for incident delirium seem to differ according to pre-fracture cognitive
status. The use of vasopressors during surgery and/or postoperative hypertension
is associated with new-onset dementia after hip fracture.
PMID- 28700611
TI - In vivo calcium imaging from dentate granule cells with wide-field fluorescence
microscopy.
AB - A combination of genetically-encoded calcium indicators and micro-optics has
enabled monitoring of large-scale dynamics of neuronal activity from behaving
animals. In these studies, wide-field microscopy is often used to visualize
neural activity. However, this method lacks optical sectioning capability, and
therefore its axial resolution is generally poor. At present, it is unclear
whether wide-field microscopy can visualize activity of densely packed small
neurons at cellular resolution. To examine the applicability of wide-field
microscopy for small-sized neurons, we recorded calcium activity of dentate
granule cells having a small soma diameter of approximately 10 micrometers. Using
a combination of high numerical aperture (0.8) objective lens and independent
component analysis-based image segmentation technique, activity of putative
single granule cell activity was separated from wide-field calcium imaging data.
The result encourages wider application of wide-field microscopy in in vivo
neurophysiology.
PMID- 28700612
TI - Assessing development assistance for child survival between 2000 and 2014: A
multi-sectoral perspective.
AB - BACKGROUND: The majority of Countdown countries did not reach the fourth
Millennium Development Goal (MDG 4) on reducing child mortality, despite the fact
that donor funding to the health sector has drastically increased. When tracking
aid invested in child survival, previous studies have exclusively focused on aid
targeting reproductive, maternal, newborn, and child health (RMNCH). We take a
multi-sectoral approach and extend the estimation to the four sectors that
determine child survival: health (RMNCH and non-RMNCH), education, water and
sanitation, and food and humanitarian assistance (Food/HA). METHODS AND FINDINGS:
Using donor reported data, obtained mainly from the OECD Creditor Reporting
System and Development Assistance Committee, we tracked the level and trends of
aid (in grants or loans) disbursed to each of the four sectors at the global,
regional, and country levels. We performed detailed analyses on missing data and
conducted imputation with various methods. To identify aid projects for RMNCH, we
developed an identification strategy that combined keyword searches and manual
coding. To quantify aid for RMNCH in projects with multiple purposes, we adopted
an integrated approach and produced the lower and upper bounds of estimates for
RMNCH, so as to avoid making assumptions or using weak evidence for allocation.
We checked the sensitivity of trends to the estimation methods and compared our
estimates to that produced by other studies. Our study yielded time-series and
recipient-specific annual estimates of aid disbursed to each sector, as well as
their lower- and upper-bounds in 134 countries between 2000 and 2014, with a
specific focus on Countdown countries. We found that the upper-bound estimates of
total aid disbursed to the four sectors in 134 countries rose from US$ 22.62
billion in 2000 to US$ 59.29 billion in 2014, with the increase occurring in all
income groups and regions with sub-Saharan Africa receiving the largest sum. Aid
to RMNCH has experienced the fastest growth (12.4%), followed by aid to Food/HA
(9.4%), education (5.1%), and water and sanitation (5.0%). With the exception of
RMNCH, the average per capita aid disbursed to each sector in the 74 Countdown
countries was smaller than in non-Countdown countries. While countries with a
large number of child deaths tend to receive the largest amount of disbursements,
non-Countdown countries with small populations usually received the highest level
of per capita aid for child survival among all 134 countries. Compared to other
Countdown countries, those that met MDG 4 with a high reliance on health aid
received much higher per capita aid across all sectors. These findings are robust
to estimation methods. CONCLUSIONS: The study suggests that to improve child
survival, better targeted investments should be made in the four sectors, and aid
to non-health sectors could be a possible contributor to child mortality
reduction. We recommend that future studies on tracking aid for child survival go
beyond the health sector and include other sectors that directly affect child
survival. Investigation should also be made about the link between aid to each of
the four sectors and child mortality reduction.
PMID- 28700613
TI - The association between resting functional connectivity and dispositional
optimism.
AB - Dispositional optimism is an individual characteristic that plays an important
role in human experience. Optimists are people who tend to hold positive
expectations for their future. Previous studies have focused on the neural basis
of optimism, such as task response neural activity and brain structure volume.
However, the functional connectivity between brain regions of the dispositional
optimists are poorly understood. Previous study suggested that the ventromedial
prefrontal cortex (vmPFC) are associated with individual differences in
dispositional optimism, but it is unclear whether there are other brain regions
that combine with the vmPFC to contribute to dispositional optimism. Thus, the
present study used the resting-state functional connectivity (RSFC) approach and
set the vmPFC as the seed region to examine if differences in functional brain
connectivity between the vmPFC and other brain regions would be associated with
individual differences in dispositional optimism. The results found that
dispositional optimism was significantly positively correlated with the strength
of the RSFC between vmPFC and middle temporal gyrus (mTG) and negativly
correlated with RSFC between vmPFC and inferior frontal gyrus (IFG). These
findings may be suggested that mTG and IFG which associated with emotion
processes and emotion regulation also play an important role in the dispositional
optimism.
PMID- 28700614
TI - Aphid symbionts and endogenous resistance traits mediate competition between
rival parasitoids.
AB - Insects use endogenous mechanisms and infection with protective symbionts to
thwart attacks from natural enemies. Defenses that target specific enemies,
however, potentially mediate competition between rivals and thereby impact
community composition. Following its introduction to North America to control pea
aphids (Acyrthosiphon pisum), the parasitoid Aphidius ervi competitively
displaced other parasitoids, except for the native Praon pequodorum. The pea
aphid exhibits tremendous clonal variation in resistance to A. ervi, primarily
through infection with the heritable bacterial symbiont Hamiltonella defensa,
although some symbiont-free aphid genotypes encode endogenous resistance.
Interestingly, H. defensa strains and aphid genotypes that protect against A.
ervi, provide no protection against the closely related, P. pequodorum. Given the
specificity of aphid defenses, we hypothesized that aphid resistance traits may
contribute to the continued persistence of P. pequodorum. We conducted
multiparasitism assays to determine whether aphid resistance traits mediate
internal competition between these two solitary parasitoid species, but found
this was not the case; P. pequodorum was the successful internal competitor
across lines varying in susceptibility to A. ervi. Next, to determine whether
resistance traits influence competitive interactions resulting in the stable
persistence of P. pequodorum, we established replicated cages varying in the
proportion of resistant aphids and recorded successful parasitism for each wasp
species over time. As expected, A. ervi outcompeted P. pequodorum in cages
containing only susceptible aphids. However, P. pequodorum not only persisted,
but was the superior competitor in populations containing any proportion (20
100%) of resistant aphids (20-100%). Smaller scale, better replicated competition
cage studies corroborated this finding, and no-competition and behavioral assays
provide insight into the processes mediating competition. Genetic variation,
including that acquired via infection with protective symbionts, may provide a
supply of hosts susceptible only to particular enemies, mediating competition
with effects on community richness and stability.
PMID- 28700615
TI - Astrocyte heterogeneity across the brain and spinal cord occurs developmentally,
in adulthood and in response to demyelination.
AB - Astrocytes have emerged as essential regulators of function and response to
injury in the brain and spinal cord, yet very little is known about regional
differences that exist. Here we compare the expression of key astroglial markers
(glial fibrillary acidic protein (GFAP) and Aldehyde Dehydrogenase-1 Family
Member L1 (ALDH1L1)) across these disparate poles of the neuraxis, tracking their
expression developmentally and in the context of demyelination. In addition, we
document changes in the astrocyte regulatory cytokine interleukin 6 (IL-6), and
its signaling partner signal transducer and activator of transcription 3 (STAT3),
in vivo and in vitro. Results demonstrate that GFAP expression is higher in the
developing and adult spinal cord relative to brain. Comparisons between GFAP and
ALDH1L1 expression suggest elevations in spinal cord GFAP during the early
postnatal period reflect an accelerated appearance of astrocytes, while
elevations in adulthood reflect higher expression by individual astrocytes.
Notably, increases in spinal cord compared to whole brain GFAP were paralleled by
higher levels of IL-6 and STAT3. Equivalent elevations in GFAP, GFAP/ALDH1L1
ratios, and in IL-6, were observed in primary astrocyte cultures derived from
spinal cord compared to cortex. Also, higher levels of GFAP were observed in the
spinal cord compared to the brain after focal demyelinating injury. Altogether,
these studies point to key differences in astrocyte abundance and the expression
of GFAP and IL-6 across the brain and spinal cord that are positioned to
influence regional specialization developmentally and responses occurring in the
context of injury and disease.
PMID- 28700616
TI - Natural variation in a single amino acid substitution underlies physiological
responses to topoisomerase II poisons.
AB - Many chemotherapeutic drugs are differentially effective from one patient to the
next. Understanding the causes of this variability is a critical step towards the
development of personalized treatments and improvements to existing medications.
Here, we investigate sensitivity to a group of anti-neoplastic drugs that target
topoisomerase II using the model organism Caenorhabditis elegans. We show that
wild strains of C. elegans vary in their sensitivity to these drugs, and we use
an unbiased genetic approach to demonstrate that this natural variation is
explained by a methionine-to-glutamine substitution in topoisomerase II (TOP-2).
The presence of a non-polar methionine at this residue increases hydrophobic
interactions between TOP-2 and its poison etoposide, as compared to a polar
glutamine. We hypothesize that this stabilizing interaction results in increased
genomic instability in strains that contain a methionine residue. The residue
affected by this substitution is conserved from yeast to humans and is one of the
few differences between the two human topoisomerase II isoforms (methionine in
hTOPIIalpha and glutamine in hTOPIIbeta). We go on to show that this amino acid
difference between the two human topoisomerase isoforms influences cytotoxicity
of topoisomerase II poisons in human cell lines. These results explain why
hTOPIIalpha and hTOPIIbeta are differentially affected by various poisons and
demonstrate the utility of C. elegans in understanding the genetics of drug
responses.
PMID- 28700617
TI - A new analysis of heart rate variability in the assessment of fetal
parasympathetic activity: An experimental study in a fetal sheep model.
AB - Analysis of heart rate variability (HRV) is a recognized tool in the assessment
of autonomic nervous system (ANS) activity. Indeed, both time and spectral
analysis techniques enable us to obtain indexes that are related to the way the
ANS regulates the heart rate. However, these techniques are limited in terms of
the lack of thresholds of the numerical indexes, which is primarily due to high
inter-subject variability. We proposed a new fetal HRV analysis method related to
the parasympathetic activity of the ANS. The aim of this study was to evaluate
the performance of our method compared to commonly used HRV analysis, with regard
to i) the ability to detect changes in ANS activity and ii) inter-subject
variability. This study was performed in seven sheep fetuses. In order to
evaluate the sensitivity and specificity of our index in evaluating
parasympathetic activity, we directly administered 2.5 mg intravenous atropine,
to inhibit parasympathetic tone, and 5 mg propranolol to block sympathetic
activity. Our index, as well as time analysis (root mean square of the successive
differences; RMSSD) and spectral analysis (high frequency (HF) and low frequency
(LF) spectral components obtained via fast Fourier transform), were measured
before and after injection. Inter-subject variability was estimated by the
coefficient of variance (%CV). In order to evaluate the ability of HRV parameters
to detect fetal parasympathetic decrease, we also estimated the effect size for
each HRV parameter before and after injections. As expected, our index, the HF
spectral component, and the RMSSD were reduced after the atropine injection.
Moreover, our index presented a higher effect size. The %CV was far lower for our
index than for RMSSD, HF, and LF. Although LF decreased after propranolol
administration, fetal stress index, RMSSD, and HF were not significantly
different, confirming the fact that those indexes are specific to the
parasympathetic nervous system. In conclusion, our method appeared to be
effective in detecting parasympathetic inhibition. Moreover, inter-subject
variability was much lower, and effect size higher, with our method compared to
other HRV analysis methods.
PMID- 28700618
TI - Micro Finite Element models of the vertebral body: Validation of local
displacement predictions.
AB - The estimation of local and structural mechanical properties of bones with micro
Finite Element (microFE) models based on Micro Computed Tomography images depends
on the quality bone geometry is captured, reconstructed and modelled. The aim of
this study was to validate microFE models predictions of local displacements for
vertebral bodies and to evaluate the effect of the elastic tissue modulus on
model's predictions of axial forces. Four porcine thoracic vertebrae were axially
compressed in situ, in a step-wise fashion and scanned at approximately 39MUm
resolution in preloaded and loaded conditions. A global digital volume
correlation (DVC) approach was used to compute the full-field displacements.
Homogeneous, isotropic and linear elastic microFE models were generated with
boundary conditions assigned from the interpolated displacement field measured
from the DVC. Measured and predicted local displacements were compared for the
cortical and trabecular compartments in the middle of the specimens. Models were
run with two different tissue moduli defined from microindentation data (12.0GPa)
and a back-calculation procedure (4.6GPa). The predicted sum of axial reaction
forces was compared to the experimental values for each specimen. MicroFE models
predicted more than 87% of the variation in the displacement measurements (R2 =
0.87-0.99). However, model predictions of axial forces were largely overestimated
(80-369%) for a tissue modulus of 12.0GPa, whereas differences in the range 10
80% were found for a back-calculated tissue modulus. The specimen with the lowest
density showed a large number of elements strained beyond yield and the highest
predictive errors. This study shows that the simplest microFE models can
accurately predict quantitatively the local displacements and qualitatively the
strain distribution within the vertebral body, independently from the considered
bone types.
PMID- 28700619
TI - Intra-operative multi-site stimulation: Expanding methodology for cortical brain
mapping of language functions.
AB - Direct cortical stimulation (DCS) is considered the gold-standard for functional
cortical mapping during awake surgery for brain tumor resection. DCS is performed
by stimulating one local cortical area at a time. We present a feasibility study
using an intra-operative technique aimed at improving our ability to map brain
functions which rely on activity in distributed cortical regions. Following
standard DCS, Multi-Site Stimulation (MSS) was performed in 15 patients by
applying simultaneous cortical stimulations at multiple locations. Language
functioning was chosen as a case-cognitive domain due to its relatively well
known cortical organization. MSS, performed at sites that did not produce
disruption when applied in a single stimulation point, revealed additional
language dysfunction in 73% of the patients. Functional regions identified by
this technique were presumed to be significant to language circuitry and were
spared during surgery. No new neurological deficits were observed in any of the
patients following surgery. Though the neuro-electrical effects of MSS need
further investigation, this feasibility study may provide a first step towards
sophistication of intra-operative cortical mapping.
PMID- 28700620
TI - Correction: Functional male accessory glands and fertility in Drosophila require
novel ecdysone receptor.
AB - [This corrects the article DOI: 10.1371/journal.pgen.1006788.].
PMID- 28700621
TI - The impact of hemodialysis schedules on the day of the week of hospitalization
for cardiovascular and infectious diseases, over a period of 20 years.
AB - There have been no studies as yet that have evaluated how hemodialysis (HD)
schedules affect the day of the week of hospitalization for cardiovascular
diseases (CVDs) and infectious diseases (IDs), over a period of time. Herein, we
performed a retrospective observational cohort study (1995-2014) evaluating
11,111 hospitalizations in 1,953 patients with end-stage renal disease, receiving
HD 3 times a week (following either a Monday-Wednesday-Friday [MWF] schedule or a
Tuesday-Thursday-Saturday [TTS] schedule) or receiving frequent HD (FHD) at least
4 times a week. Overall, hospitalization rates for CVDs and IDs were the highest
on Monday in the MWF schedule and Tuesday in the TTS schedule compared to the
average rates for all the days of the week. When generalized estimating equations
(GEEs) were used in conjunction with robust variance estimators of each type of
CVD, the risk for pulmonary edema was found to be significantly higher on Sunday
and Monday in the MWF schedule and Monday and Tuesday in the TTS schedule. For
both cerebrovascular and ischemic heart disease, the risks were significantly
higher on Tuesday in the MWF schedule and Wednesday in the TTS schedule.
Moreover, there were significant differences in the day of the week risks among
the various CVD types. On trend analysis, the overall hospitalization rate for
CVDs on the first HD day did not decrease (P = 0.2); however, the hospitalization
rate for IDs on the first HD day significantly decreased (P = 0.02) over a span
of 20 years. When GEEs were used in the case of FHD patients with severe heart
failure, the hospitalization rate on the first HD day (Monday) significantly
decreased after FHD initiation (P = 0.04). It was found that HD schedules
affected the day of the week of hospitalization for CVDs. FHD may lower the day
of the week risk.
PMID- 28700622
TI - Modelling the emergence of influenza drug resistance: The roles of surface
proteins, the immune response and antiviral mechanisms.
AB - The emergence of influenza drug resistance has become of particular interest as
current planning for an influenza pandemic involves using massive amounts of
antiviral drugs. We use semi-stochastic simulations to examine the emergence of
drug resistant mutants during the course of a single infection within a patient
in the presence and absence of antiviral therapy. We specifically examine three
factors and their effect on the emergence of drug-resistant mutants: antiviral
mechanism, the immune response, and surface proteins. We find that adamantanes,
because they act at the start of the replication cycle to prevent infection, are
less likely to produce drug-resistant mutants than NAIs, which act at the end of
the replication cycle. A mismatch between surface proteins and internal RNA
results in drug-resistant mutants being less likely to emerge, and emerging later
in the infection because the mismatch gives antivirals a second chance to prevent
propagation of the mutation. The immune response subdues slow growing infections,
further reducing the probability that a drug resistant mutant will emerge and
yield a drug-resistant infection. These findings improve our understanding of the
factors that contribute to the emergence of drug resistance during the course of
a single influenza infection.
PMID- 28700623
TI - Utilization of genetic data can improve the prediction of type 2 diabetes
incidence in a Swedish cohort.
AB - The aim of this study was to measure the impact of genetic data in improving the
prediction of type 2 diabetes (T2D) in the Malmo Diet and Cancer Study cohort.
The current study was performed in 3,426 Swedish individuals and utilizes of a
set of genetic and environmental risk data. We first validated our environmental
risk model by comparing it to both the Finnish Diabetes Risk Score and the T2D
risk model derived from the Framingham Offspring Study. The area under the curve
(AUC) for our environmental model was 0.72 [95% CI, 0.69-0.74], which was
significantly better than both the Finnish (0.64 [95% CI, 0.61-0.66], p-value < 1
x 10-4) and Framingham (0.69 [95% CI, 0.66-0.71], p-value = 0.0017) risk scores.
We then verified that the genetic data has a statistically significant positive
correlation with incidence of T2D in the studied population. We also verified
that adding genetic data slightly but statistically increased the AUC of a model
based only on environmental risk factors (RFs, AUC shift +1.0% from 0.72 to 0.73,
p-value = 0.042). To study the dependence of the results on the environmental
RFs, we divided the population into two equally sized risk groups based only on
their environmental risk and repeated the same analysis within each
subpopulation. While there is a statistically significant positive correlation
between the genetic data and incidence of T2D in both environmental risk
categories, the positive shift in the AUC remains statistically significant only
in the category with the lower environmental risk. These results demonstrate that
genetic data can be used to increase the accuracy of T2D prediction. Also, the
data suggests that genetic data is more valuable in improving T2D prediction in
populations with lower environmental risk. This suggests that the impact of
genetic data depends on the environmental risk of the studied population and thus
genetic association studies should be performed in light of the underlying
environmental risk of the population.
PMID- 28700624
TI - Intergroup contact throughout the lifespan modulates implicit racial biases
across perceivers' racial group.
AB - Few researchers have investigated how contact across the lifespan influences
racial bias and whether diversity of contact is beneficial regardless of the race
of the perceiver. This research aims to address these gaps in the literature with
a focus on how diversity in childhood and current contact shapes implicit racial
bias across perceivers' racial group. In two investigations, participants
completed an Implicit Association Test and a self-report measure of the racial
diversity of their current and childhood contact. In both studies, increased
contact with Black compared with White individuals, both in childhood (Study 2)
and currently (Studies 1 and 2), was associated with reduced implicit pro-White
racial bias. For Black individuals (Study 2) more contact with Black compared
with White individuals also was associated with reduced implicit pro-White racial
bias. These findings suggest that diversity in contact across the lifespan may be
related to reductions in implicit racial biases and that this relationship may
generalize across racial groups.
PMID- 28700625
TI - Pooling strategy and chromosome painting characterize a living zebroid for the
first time.
AB - We have investigated the complex karyotype of a living zebra-donkey hybrid for
the first time using chromosome-specific painting probes produced from flow
sorted chromosomes from a zebra (Equus burchelli) and horse (Equus caballus). As
the chromosomes proved difficult to distinguish from one another, a successful
new strategy was devised to resolve the difficulty and characterize each
chromosome. This was based on selecting five panels of whole chromosome painting
probes that could differentiate zebra and donkey chromosomes by labelling the
probes with either FITC or Cy3 fluorochromes. Each panel was hybridized
sequentially to the same G-Q-banded metaphases and the results combined so that
every zebra and donkey chromosome in each suitable metaphase could be identified.
A diploid number of 2n = 53, XY was found, containing haploid sets of 22
chromosomes from the zebra and 31 chromosomes from the donkey, without evidence
of chromosome rearrangement. This new strategy, developed for the first time, may
have several applications in the resolution of other complex hybrid karyotypes
and chromosomal aberrations.
PMID- 28700626
TI - Correction: 1.2 million kids and counting-Mobile science laboratories drive
student interest in STEM.
AB - [This corrects the article DOI: 10.1371/journal.pbio.2001692.].
PMID- 28700627
TI - Network analysis of exploratory behaviors of mice in a spatial learning and
memory task.
AB - The Barnes maze is one of the main behavioral tasks used to study spatial
learning and memory. The Barnes maze is a task conducted on "dry land" in which
animals try to escape from a brightly lit exposed circular open arena to a small
dark escape box located under one of several holes at the periphery of the arena.
In comparison with another classical spatial learning and memory task, the Morris
water maze, the negative reinforcements that motivate animals in the Barnes maze
are less severe and less stressful. Furthermore, the Barnes maze is more
compatible with recently developed cutting-edge techniques in neural circuit
research, such as the miniature brain endoscope or optogenetics. For this study,
we developed a lift-type task start system and equipped the Barnes maze with it.
The subject mouse is raised up by the lift and released into the maze
automatically so that it can start navigating the maze smoothly from exactly the
same start position across repeated trials. We believe that a Barnes maze test
with a lift-type task start system may be useful for behavioral experiments when
combined with head-mounted or wire-connected devices for online imaging and
intervention in neural circuits. Furthermore, we introduced a network analysis
method for the analysis of the Barnes maze data. Each animal's exploratory
behavior in the maze was visualized as a network of nodes and their links, and
spatial learning in the maze is described by systematic changes in network
structures of search behavior. Network analysis was capable of visualizing and
quantitatively analyzing subtle but significant differences in an animal's
exploratory behavior in the maze.
PMID- 28700628
TI - Asiatic acid protects against cognitive deficits and reductions in cell
proliferation and survival in the rat hippocampus caused by 5-fluorouracil
chemotherapy.
AB - The chemotherapy drug, 5-fluorouracil (5-FU), has been reported to cause
cognitive impairments in cancer patients. The drug also reduces cell
proliferation and survival in the brain. Asiatic acid (AA) is a triterpene
compound found in Centella asiatica that can protect against reduction of
neurogenesis in the hippocampus and memory deficits induced by valproic acid
(VPA). In the present study, we investigated the preventive effects of AA on the
deficits in spatial working memory and cell proliferation and survival caused by
5-FU chemotherapy in a rat model. Male Sprague Dawley rats received 5-FU (5 i.v.
injections, 25 mg/kg) on day 8, 11, 14, 17 and 20 of the study. This was co
administered with AA (30 mg/kg, oral gavage tube) either 20 days before receiving
5-FU (preventive), after receiving 5-FU (recovery), or for the entire period of
the experiment (throughout). Spatial working memory was determined using the
novel object location (NOL) test and hippocampal cell proliferation and survival
of dividing cells were quantified using immunohistochemistry. Rats in the 5-FU
alone and recovery groups showed memory deficits in the NOL test and reductions
in cell proliferation and cell survival in the subgranular zone (SGZ) of the
hippocampal dentate gyrus. Rats in the control, AA alone, and both preventive and
throughout co-administration groups, however, did not exhibit these
characteristics. The results showed that 5-FU chemotherapy impaired memory and
reduced cell proliferation and cell survival in the SGZ of the hippocampal
dentate gyrus. However, these impairments in the animals receiving 5-FU
chemotherapy were restored to control levels when AA was co-administered before
and during 5-FU treatment. These data demonstrate that AA can prevent the spatial
working memory and hippocampal neurogenesis impairments caused by 5-FU
chemotherapy.
PMID- 28700629
TI - Escherichia coli DNA ligase B may mitigate damage from oxidative stress.
AB - Escherichia coli encodes two DNA ligases, ligase A, which is essential under
normal laboratory growth conditions, and ligase B, which is not. Here we report
potential functions of ligase B. We found that across the entire
Enterobacteriaceae family, ligase B is highly conserved in both amino acid
identity and synteny with genes associated with oxidative stress. Deletion of
ligB sensitized E. coli to specific DNA damaging agents and antibiotics resulted
in a weak mutator phenotype, and decreased biofilm formation. Overexpression of
ligB caused a dramatic extension of lag phase that eventually resumed normal
growth. The ligase function of ligase B was not required to mediate the extended
lag phase, as overexpression of a ligase-deficient ligB mutant also blocked
growth. Overexpression of ligB during logarithmic growth caused an immediate
block of cell growth and DNA replication, and death of about half of cells. These
data support a potential role for ligase B in the base excision repair pathway or
the mismatch repair pathway.
PMID- 28700630
TI - Simulating ideal assistive devices to reduce the metabolic cost of walking with
heavy loads.
AB - Wearable robotic devices can restore and enhance mobility. There is growing
interest in designing devices that reduce the metabolic cost of walking; however,
designers lack guidelines for which joints to assist and when to provide the
assistance. To help address this problem, we used musculoskeletal simulation to
predict how hypothetical devices affect muscle activity and metabolic cost when
walking with heavy loads. We explored 7 massless devices, each providing
unrestricted torque at one degree of freedom in one direction (hip abduction, hip
flexion, hip extension, knee flexion, knee extension, ankle plantarflexion, or
ankle dorsiflexion). We used the Computed Muscle Control algorithm in OpenSim to
find device torque profiles that minimized the sum of squared muscle activations
while tracking measured kinematics of loaded walking without assistance. We then
examined the metabolic savings provided by each device, the corresponding device
torque profiles, and the resulting changes in muscle activity. We found that the
hip flexion, knee flexion, and hip abduction devices provided greater metabolic
savings than the ankle plantarflexion device. The hip abduction device had the
greatest ratio of metabolic savings to peak instantaneous positive device power,
suggesting that frontal-plane hip assistance may be an efficient way to reduce
metabolic cost. Overall, the device torque profiles generally differed from the
corresponding net joint moment generated by muscles without assistance, and
occasionally exceeded the net joint moment to reduce muscle activity at other
degrees of freedom. Many devices affected the activity of muscles elsewhere in
the limb; for example, the hip flexion device affected muscles that span the
ankle joint. Our results may help experimentalists decide which joint motions to
target when building devices and can provide intuition for how devices may
interact with the musculoskeletal system. The simulations are freely available
online, allowing others to reproduce and extend our work.
PMID- 28700631
TI - Is the level of knowledge a predictor of rational antibiotic use in Serbia?
AB - INTRODUCTION: The objective of this study was to investigate the knowledge,
attitudes and behavior regarding antibiotics of the general population. METHODS:
The study sample consisted of adult subjects who consulted general practitioners
at health centers in Serbia and agreed to complete the questionnaire. A total of
668 questionnaires were distributed; 500 respondents completed the entire
questionnaire (response rate 74.85%). RESULTS: The average age was 51.65 +/-
16.56 years, 60.80% of the respondents were women. The median antibiotic
knowledge score was 9. Predictors of adequate antibiotic knowledge were higher
education level and a family member whose ocuppation was related to health-care.
Overall, 58.4% of respondents believed that antibiotics could be used to treat
common cold. Around a half of the respondents (47.2%) self-medicated with
antibiotics at least once during their life-time, and around a quarter (24.2%)
during the last treatment of infection. Patients with inadequate knowledge had 3
times higher chances of self-medicating with antibiotics compared to those with
adequate knowledge. Although 98.20% of respondents claimed that antibiotic
treatment should be started after a visit to a doctor and receiving a
prescription, only 65.8% obtained antibiotics with prescription from a doctor
during the last infection. CONCLUSIONS: Although these results demonstrate that
respondents had a relatively adequate level of knowledge regarding antibiotics
use, some areas of misconceptions and improper behavior were identified.
Therefore, further rationalization should be focused on educational campaigns
targeting the behavior of patients with regard to antibiotic use.
PMID- 28700632
TI - Inflammation dependent mTORC1 signaling interferes with the switch from
keratinocyte proliferation to differentiation.
AB - Psoriasis is a frequent and often severe inflammatory skin disease, characterized
by altered epidermal homeostasis. Since we found previously that Akt/mTOR
signaling is hyperactivated in psoriatic skin, we aimed at elucidating the role
of aberrant mTORC1 signaling in this disease. We found that under healthy
conditions mTOR signaling was shut off when keratinocytes switch from
proliferation to terminal differentiation. Inflammatory cytokines (IL-1beta, IL
17A, TNF-alpha) induced aberrant mTOR activity which led to enhanced
proliferation and reduced expression of differentiation markers. Conversely,
regular differentiation could be restored if mTORC1 signaling was blocked. In
mice, activation of mTOR through the agonist MHY1485 also led to aberrant
epidermal organization and involucrin distribution. In summary, these results not
only identify mTORC1 as an important signal integrator pivotal for the cells fate
to either proliferate or differentiate, but emphasize the role of inflammation
dependent mTOR activation as a psoriatic pathomechanism.
PMID- 28700633
TI - Effects of the lateral amplitude and regularity of upper body fluctuation on step
time variability evaluated using return map analysis.
AB - The aim of this study was to evaluate the effects of the lateral amplitude and
regularity of upper body fluctuation on step time variability. Return map
analysis was used to clarify the relationship between step time variability and a
history of falling. Eleven healthy, community-dwelling older adults and twelve
younger adults participated in the study. All of the subjects walked 25 m at a
comfortable speed. Trunk acceleration was measured using triaxial accelerometers
attached to the third lumbar vertebrae (L3) and the seventh cervical vertebrae
(C7). The normalized average magnitude of acceleration, the coefficient of
determination ($R^2$) of the return map, and the step time variabilities, were
calculated. Cluster analysis using the average fluctuation and the regularity of
C7 fluctuation identified four walking patterns in the mediolateral (ML)
direction. The participants with higher fluctuation and lower regularity showed
significantly greater step time variability compared with the others.
Additionally, elderly participants who had fallen in the past year had higher
amplitude and a lower regularity of fluctuation during walking. In conclusion, by
focusing on the time evolution of each step, it is possible to understand the
cause of stride and/or step time variability that is associated with a risk of
falls.
PMID- 28700634
TI - Differential modulation of the lactisole 'Sweet Water Taste' by sweeteners.
AB - Pre-exposure to taste stimuli and certain chemicals can cause water to have a
taste. Here we studied further the 'sweet water taste' (SWT) perceived after
exposure to the sweet taste inhibitor lactisole. Experiment 1 investigated an
incidental observation that presenting lactisole in mixture with sucrose reduced
the intensity of the SWT. The results confirmed this observation and also showed
that rinsing with sucrose after lactisole could completely eliminate the SWT. The
generalizability of these findings was investigated in experiment 2 by presenting
5 additional sweeteners before, during, or after exposure to lactisole. The
results found with sucrose were replicated with fructose and cyclamate, but the 3
other sweeteners were less effective suppressors of the SWT, and the 2 sweeteners
having the highest potency initially enhanced it. A third experiment investigated
these interactions on the tongue tip and found that the lactisole SWT was
perceived only when water was actively flowed across the tongue. The same
experiment yielded evidence against the possibility that suppression of the SWT
following exposure to sweeteners is an aftereffect of receptor activation while
providing additional support for a role of sweetener potency. Collectively these
results provide new evidence that complex inhibitory and excitatory interactions
occur between lactisole and agonists of the sweet taste receptor TAS1R2-TAS1R3.
Receptor mechanisms that may be responsible for these interactions are discussed
in the context of the current model of the SWT and the possible contribution of
allosteric modulation.
PMID- 28700635
TI - The quantitative impact of read mapping to non-native reference genomes in
comparative RNA-Seq studies.
AB - Sequence read alignment to a reference genome is a fundamental step in many
genomics studies. Accuracy in this fundamental step is crucial for correct
interpretation of biological data. In cases where two or more closely related
bacterial strains are being studied, a common approach is to simply map reads
from all strains to a common reference genome, whether because there is no closed
reference for some strains or for ease of comparison. The assumption is that the
differences between bacterial strains are insignificant enough that the results
of differential expression analysis will not be influenced by choice of
reference. Genes that are common among the strains under study are used for
differential expression analysis, while the remaining genes, which may fail to
express in one sample or the other because they are simply absent, are analyzed
separately. In this study, we investigate the practice of using a common
reference in transcriptomic analysis. We analyze two multi-strain transcriptomic
data sets that were initially presented in the literature as comparisons based on
a common reference, but which have available closed genomic sequence for all
strains, allowing a detailed examination of the impact of reference choice. We
provide a method for identifying regions that are most affected by non-native
alignments, leading to false positives in differential expression analysis, and
perform an in depth analysis identifying the extent of expression loss. We also
simulate several data sets to identify best practices for non-native reference
use.
PMID- 28700636
TI - Large-scale ex vivo generation of human neutrophils from cord blood CD34+ cells.
AB - Conventional high-dose chemotherapy frequently leads to severe neutropenia,
during which patients experience a high risk of infection. Although support care
with donor's neutrophils is possible this choice is largely hampered by the
limited availability of matched donors. To overcome this problem, we explored a
large-scale ex vivo production of neutrophils from hematopoietic stem cells
(HSCs) using a four-stage culture approach in a roller-bottle production
platform. We expanded CD34+ HSCs isolated from umbilical cord blood (UCB) using
our in-house special medium supplemented with cytokine cocktails and achieved
about 49000-fold expansion of cells, among which about 61% were differentiated
mature neutrophils. Ex vivo differentiated neutrophils exhibited a chemotactic
activity similar to those from healthy donors and were capable of killing E. coli
in vitro. The expansion yield as reported herein was at least 5 times higher than
any other methods reported in the literature. Moreover, the cost of our modified
medium was only a small fraction (<1/60) of the StemSpanTM SFEM. Therefore, our
ex vivo expansion platform, coupled with a low cost of stem cell culture due to
the use of a modified medium, makes large-scale manufacturing neutrophils
possible, which should be able to greatly ameliorate neutrophil shortage for
transfusion in the clinic.
PMID- 28700637
TI - Contingent association between the size of the social support network and
osteoporosis among Korean elderly women.
AB - OBJECTIVE: To investigate the association between the number of personal ties (or
the size of the social support network) and the incidence of osteoporosis among
older women in Korea. METHODS: Data from the Korean Urban Rural Elderly Study
were used. Bone density was measured by dual-energy X-ray absorptiometry at the
lumbar spine (L1-L4) and femur neck. T-score, the standardized bone density
compared with what is normally expected in a healthy young adult, was measured
and the presence of osteoporosis was determined, if the T-score was < -2.5. The
social support network size was measured by self-responses (number of confidants
and spouse). RESULTS: Of the 1,846 participants, 44.9% were diagnosed with
osteoporosis. The association between the social support network size and the
incidence of osteoporosis was curvilinear in both bivariate and multivariate
analyses. Having more people in one's social support network size was associated
with lower risk of osteoporosis until it reached around four. Increasing the
social support network size beyond four, in contrast, was associated with a
higher risk of osteoporosis. This association was contingent on the average
intimacy level of the social network. At the highest average intimacy level
("extremely close"), increasing the number of social support network members from
one to six was associated with linear decrease in the predicted probability of
osteoporosis from 45% to 30%. However, at the lowest average intimacy level ("not
very close"), the predicted probability of osteoporosis dramatically increased
from 48% to 80% as the size of the social network increased from one to six.
CONCLUSION: Our results show that maintaining a large and intimate social support
network is associated with a lower risk of osteoporosis among elderly Korean
women, while a large but less-intimate social relationship is associated with a
higher risk.
PMID- 28700638
TI - Ijuhya vitellina sp. nov., a novel source for chaetoglobosin A, is a destructive
parasite of the cereal cyst nematode Heterodera filipjevi.
AB - Cyst nematodes are globally important pathogens in agriculture. Their sedentary
lifestyle and long-term association with the roots of host plants render cyst
nematodes especially good targets for attack by parasitic fungi. In this context
fungi were specifically isolated from nematode eggs of the cereal cyst nematode
Heterodera filipjevi. Here, Ijuhya vitellina (Ascomycota, Hypocreales,
Bionectriaceae), encountered in wheat fields in Turkey, is newly described on the
basis of phylogenetic analyses, morphological characters and life-style related
inferences. The species destructively parasitises eggs inside cysts of H.
filipjevi. The parasitism was reproduced in in vitro studies. Infected eggs were
found to harbour microsclerotia produced by I. vitellina that resemble long-term
survival structures also known from other ascomycetes. Microsclerotia were also
formed by this species in pure cultures obtained from both, solitarily isolated
infected eggs obtained from fields and artificially infected eggs. Hyphae
penetrating the eggshell colonised the interior of eggs and became transformed
into multicellular, chlamydospore-like structures that developed into
microsclerotia. When isolated on artificial media, microsclerotia germinated to
produce multiple emerging hyphae. The specific nature of morphological structures
produced by I. vitellina inside nematode eggs is interpreted as a unique mode of
interaction allowing long-term survival of the fungus inside nematode cysts that
are known to survive periods of drought or other harsh environmental conditions.
Generic classification of the new species is based on molecular phylogenetic
inferences using five different gene regions. I. vitellina is the only species of
the genus known to parasitise nematodes and produce microsclerotia. Metabolomic
analyses revealed that within the Ijuhya species studied here, only I. vitellina
produces chaetoglobosin A and its derivate 19-O-acetylchaetoglobosin A.
Nematicidal and nematode-inhibiting activities of these compounds have been
demonstrated suggesting that the production of these compounds may represent an
adaptation to nematode parasitism.
PMID- 28700639
TI - The effects of ingestion of hormonal host factors on the longevity and
insecticide resistance phenotype of the major malaria vector Anopheles arabiensis
(Diptera: Culicidae).
AB - Exogenous vertebrate-derived factors circulating in the blood have the capacity
to modulate the biology of haematophagous insects. These include insulin, insulin
growth factor 1 (IGF) and transforming growth factor beta1 (TGFbeta). The effects
of the consumption of these three proteins were examined on laboratory strains of
Anopheles arabiensis. SENN, an insecticide susceptible strain and SENN DDT, a
resistant strain selected from SENN, were fed with host factor-supplemented
sucrose. Adult longevity was measured and insecticide resistance phenotype over
time was assessed by WHO bioassay. Detoxification and oxidative stress defence
enzyme activity was assessed calorimetrically. Insulin supplementation augmented
insecticide resistance in young adult mosquitoes. This effect was due to the
hormonal nature of the protein, as heat-denatured insulin did not elicit the same
response. In contrast, IGF and TGFbeta consumption generally reduced the
expression of insecticide resistance. Insulin ingestion significantly reduced
longevity in the insecticide susceptible strain. IGF elicited the same response
in the susceptible strain, while TGF consumption had no effect on either strain.
Consumption of all factors significantly decreased Glutathione S-transferase
activity and increased cytochrome P450 and superoxide dismutase activity. This
suggests that the altered detoxification phenotype is mediated primarily by
cytochrome P450 activity, which would result in an increase in oxidative stress.
The increased superoxide dismutase activity suggests that this enzyme class
alleviates the oxidative stress as opposed to glutathione-based redox systems.
Oxidative stress responses play a crucial role in insecticide resistance and
longevity. These data show that ingested hormonal factors can affect mosquito
longevity and insecticide susceptibility, both of which are important
characteristics in terms of malaria transmission and control.
PMID- 28700640
TI - Modeling the risk of transmission of schistosomiasis in Akure North Local
Government Area of Ondo State, Nigeria using satellite derived environmental
data.
AB - Schistosomiasis is a parasitic disease and its distribution, in space and time,
can be influenced by environmental factors such as rivers, elevation, slope, land
surface temperature, land use/cover and rainfall. The aim of this study is to
identify the areas with suitable conditions for schistosomiasis transmission on
the basis of physical and environmental factors derived from satellite imagery
and spatial analysis for Akure North Local Government Area (LGA) of Ondo State.
Nigeria. This was done through methodology multicriteria evaluation (MCE) using
Saaty's analytical hierarchy process (AHP). AHP is a multi-criteria decision
method that uses hierarchical structures to represent a problem and makes
decisions based on priority scales. In this research AHP was used to obtain the
mapping weight or importance of each individual schistosomiasis risk factor. For
the purpose of identifying areas of schistosomiasis risk, this study focused on
temperature, drainage, elevation, rainfall, slope and land use/land cover as the
factors controlling schistosomiasis incidence in the study area. It is by
reclassifying and overlaying these factors that areas vulnerable to
schistosomiasis were identified. The weighted overlay analysis was done after
each factor was given the appropriate weight derived through the analytical
hierarchical process. The prevalence of urinary schistosomiasis in the study area
was also determined by parasitological analysis of urine samples collected
through random sampling. The results showed varying risk of schistosomiasis with
a larger portion of the area (82%) falling under the high and very high risk
category. The study also showed that one community (Oba Ile) had the lowest risk
of schistosomiasis while the risk increased in the four remaining communities
(Iju, Igoba, Ita Ogbolu and Ogbese). The predictions made by the model correlated
strongly with observations from field study. The high risk zones corresponded to
known endemic communities. This study revealed that environmental factors can be
used in identifying and predicting the transmission of schistosomiasis as well as
effective monitoring of disease risk in newly established rural and agricultural
communities.
PMID- 28700641
TI - Serial DNA relay in DNA logic gates by electrical fusion and mechanical splitting
of droplets.
AB - DNA logic circuits utilizing DNA hybridization and/or enzymatic reactions have
drawn increasing attention for their potential applications in the diagnosis and
treatment of cellular diseases. The compartmentalization of such a system into a
microdroplet considerably helps to precisely regulate local interactions and
reactions between molecules. In this study, we introduced a relay approach for
enabling the transfer of DNA from one droplet to another to implement multi-step
sequential logic operations. We proposed electrical fusion and mechanical
splitting of droplets to facilitate the DNA flow at the inputs, logic operation,
output, and serial connection between two logic gates. We developed Negative-OR
operations integrated by a serial connection of the OR gate and NOT gate
incorporated in a series of droplets. The four types of input defined by the
presence/absence of DNA in the input droplet pair were correctly reflected in the
readout at the Negative-OR gate. The proposed approach potentially allows for
serial and parallel logic operations that could be used for complex diagnostic
applications.
PMID- 28700642
TI - Bacterial communities found in placental tissues are associated with severe
chorioamnionitis and adverse birth outcomes.
AB - Preterm birth is a major cause of neonatal mortality and morbidity worldwide.
Bacterial infection and the subsequent inflammatory response are recognised as an
important cause of preterm birth. It is hypothesised that these organisms ascend
the cervical canal, colonise placental tissues, cause chorioamnionitis and in
severe cases infect amniotic fluid and the foetus. However, the presence of
bacteria within the intrauterine cavity does not always precede chorioamnionitis
or preterm birth. Whereas previous studies observing the types of bacteria
present have been limited in size and the specificity of a few predetermined
organisms, in this study we characterised bacteria found in placental tissues
from a cohort of 1391 women in rural Malawi using 16S ribosomal RNA gene
sequencing. We found that specific bacteria found concurrently on placental
tissues associate with chorioamnionitis and delivery of a smaller newborn. Severe
chorioamnionitis was associated with a distinct difference in community members,
a higher bacterial load and lower species richness. Furthermore, Sneathia
sanguinengens and Peptostreptococcus anaerobius found in both matched participant
vaginal and placental samples were associated with a lower newborn length-for-age
Z-score. This is the largest study to date to examine the placental microbiome
and its impact of birth outcomes. Our results provide data on the role of the
vaginal microbiome as a source of placental infection as well as the possibility
of therapeutic interventions against targeted organisms during pregnancy.
PMID- 28700643
TI - Characterization of a panel of monoclonal antibodies recognizing specific
epitopes on GFAP.
AB - Alexander disease (AxD) is a neurodegenerative disease caused by heterozygous
mutations in the GFAP gene, which encodes the major intermediate filament protein
of astrocytes. This disease is characterized by the accumulation of cytoplasmic
protein aggregates, known as Rosenthal fibers. Antibodies specific to GFAP could
provide invaluable tools to facilitate studies of the normal biology of GFAP and
to elucidate the pathologic role of this IF protein in disease. While a large
number of antibodies to GFAP are available, few if any of them have defined
epitopes. Here we described the characterization of a panel of commonly used anti
GFAP antibodies, which recognized epitopes at regions extending across the rod
domain of GFAP. We show that all of the antibodies are useful for immunoblotting
and immunostaining, and identify a subset that preferentially recognized human
GFAP. Using these antibodies, we demonstrate the presence of biochemically
modified forms of GFAP in brains of human AxD patients and mouse AxD models.
These data suggest that this panel of anti-GFAP antibodies will be useful for
studies of animal and cell-based models of AxD and related diseases in which
cytoskeletal defects associated with GFAP modifications occur.
PMID- 28700644
TI - Transcription of putative tonoplast transporters in response to glyphosate and
paraquat stress in Conyza bonariensis and Conyza canadensis and selection of
reference genes for qRT-PCR.
AB - Herbicide resistance is a challenge for modern agriculture further complicated by
cases of resistance to multiple herbicides. Conyza bonariensis and Conyza
canadensis are invasive weeds of field crops, orchards, and non-cropped areas in
many parts of the world. In California, USA, Conyza populations resistant to the
herbicides glyphosate and paraquat have recently been described. Although the
mechanism conferring resistance to glyphosate and paraquat in these species was
not elucidated, reduced translocation of these herbicides was observed under
experimental conditions in both species. Glyphosate and paraquat resistance
associated with reduced translocation are hypothesized to be a result of
sequestration of herbicides into the vacuole, with the possible involvement of
over-expression of genes encoding tonoplast transporters of ABC-transporter
families in cases of glyphosate resistance or cationic amino acid transporters
(CAT) in cases of paraquat resistance. However, gene expression in response to
herbicide treatment has not been studied in glyphosate and paraquat resistant
populations. In the current study, we evaluated the transcript levels of genes
possibly involved in resistance using real-time PCR. First, we evaluated eight
candidate reference genes following herbicide treatment and selected three genes
that exhibited stable expression profiles; ACTIN, HEAT-SHOCK-PROTEIN-70, and
CYCLOPHILIN. The reference genes identified here can be used for further studies
related to plant-herbicide interactions. We used these reference genes to assay
the transcript levels of EPSPS, ABC transporters, and CAT in response to
herbicide treatment in susceptible and resistant Conyza spp. lines. No
transcription changes were observed in EPSPS or CAT genes after glyphosate or
paraquat treatment, suggesting that these genes are not involved in the
resistance mechanism. Transcription of the two ABC transporter genes increased
following glyphosate treatment in all Conyza spp. lines. Transcription of ABC
transporters also increased after paraquat treatment in all three lines of C.
bonariensis. However, in C. canadensis, paraquat treatment increased
transcription of only one ABC transporter gene in the susceptible line. The
increase in transcription of ABC transporters after herbicide treatment is likely
a stress response based on similar response observed across all Conyza lines
regardless of resistance or sensitivity to glyphosate or paraquat, thus these
genes do not appear to be directly involved in the mechanism of resistance in
Conyza spp.
PMID- 28700645
TI - Overweight in young males reduce fertility in rabbit model.
AB - Semen quality has certainly declined over the past few decades, possibly owing to
modern lifestyle factors. In this sense, the role of overweight and obesity in
the development of subfertility in males has generated a considerable amount of
interest in recent years. However, there is no consensus on whether overweight or
obesity impaired sperm quality. Thus, based on the ongoing debate about risk
factors for subfertility associated with overweight and obesity in men, this
study was designed to investigate the effect of overweight on sperm quality
parameters and fertility success in randomized controlled trial in a rabbit
model. Fourteen male rabbits were randomly assigned to a control group in which
nutritional requirements were satisfied or a group fed to satiety from 12 to 32
weeks of age. At 24 weeks of age, semen samples were analysed weekly by
conventional semen analysis for 8 weeks. In addition, during the trial female
rabbits were artificially inseminated by each male to assess the fertility
success and the number of offspring. Young males fed to satiety were associated
with a significant increase in body weight (13.6% overweight) and perirenal fat
thickness (5%). Male overweight presented a significant decrease in sperm
concentration. There were no differences in the remaining sperm parameters.
However, male overweight showed a clear and significant decrease in fertility
success (control group, 64+/-8.9% versus fed to satiety group, 35+/-9.2%), but
not in the number of offspring. Taken together, our findings provide new evidence
on the loss of fertility induced by overweight in males.
PMID- 28700646
TI - Efficacy and safety of micafungin versus extensive azoles in the prevention and
treatment of invasive fungal infections for neutropenia patients with
hematological malignancies: A meta-analysis of randomized controlled trials.
AB - BACKGROUND: Current studies that compare the efficacy and safety of micafungin
(MCFG) with that of triazoles for the prophylaxis and treatment of invasive
fungal infections (IFIs) demonstrate a lack of sufficient evidence and yield
conflicting results. To compare the efficacy and safety of MCFG and triazoles in
the prevention and treatment of IFIs, we conducted a meta-analysis and trial
sequential analysis (TSA). METHODS: For the meta-analysis, we systematically
searched the databases of PubMed, Embase and Cochrane Central Register of
Controlled Trials and relevant database articles for randomized controlled
studies published through November 2016. Comparative studies of the efficacy and
safety of MCFG versus triazoles in the prevention and treatment of IFIs were
selected. Meta-analysis was performed by R software with the "metafor" package.
Pooled results were expressed as risk ratios (RRs) with corresponding 95%
confidence intervals (CI). TSA was adopted to assess the studies' power with TSA
version 0.9 beta. RESULTS: Nine current studies were included in the meta
analysis (1049 cases and 959 controls). Pooled trial comparisons indicated that
MCFG does have significantly higher treatment success rates (RR = 1.13; 95% CI,
1.02-1.25; p = 0.0205) and reduces the number of overall IFIs (RR = 0.75; 95% CI,
0.61-0.92; p = 0.0056). However, MCFG demonstrates no difference in all-cause
mortality (RR = 0.76; 95% CI, 0.52-1.12, p = 0.1624). For the safety evaluation,
MCFG had a significantly lower incidence of severe adverse events (AEs) (RR =
0.45; 95% CI, 0.25-0.83; p = 0.0105), hepatic impairment (RR = 0.70; 95% CI, 0.50
0.97; p = 0.0363) and premature discontinuation (RR = 0.51; 95% CI, 0.34-0.76, p
= 0.0010). Meta-regression analysis disclosed the correction of mean age and
treatment success rates (P < 0.0001). Meanwhile, TSA demonstrated sufficient
power to show efficacy. CONCLUSIONS: The treatment success rate of MCFG is
superior to that of triazoles for the prophylaxis and treatment of IFIs, and
correction of the mean patient age demonstrates that efficacy increases as
patient age decreases. MCFG appears to be well-tolerated with manageable side
effects and lower withdrawal rates. However, additional clinical trials should be
conducted on specific drug-related mortality and AEs to gather sufficient
evidence on these matters.
PMID- 28700647
TI - Cultural effects on the association between election outcomes and face-based
trait inferences.
AB - How competent a politician looks, as assessed in the laboratory, is correlated
with whether the politician wins in real elections. This finding has led many to
investigate whether the association between candidate appearances and election
outcomes transcends cultures. However, these studies have largely focused on
European countries and Caucasian candidates. To the best of our knowledge, there
are only four cross-cultural studies that have directly investigated how face
based trait inferences correlate with election outcomes across Caucasian and
Asian cultures. These prior studies have provided some initial evidence regarding
cultural differences, but methodological problems and inconsistent findings have
complicated our understanding of how culture mediates the effects of candidate
appearances on election outcomes. Additionally, these four past studies have
focused on positive traits, with a relative neglect of negative traits, resulting
in an incomplete picture of how culture may impact a broader range of trait
inferences. To study Caucasian-Asian cultural effects with a more balanced
experimental design, and to explore a more complete profile of traits, here we
compared how Caucasian and Korean participants' inferences of positive and
negative traits correlated with U.S. and Korean election outcomes. Contrary to
previous reports, we found that inferences of competence (made by participants
from both cultures) correlated with both U.S. and Korean election outcomes.
Inferences of open-mindedness and threat, two traits neglected in previous cross
cultural studies, were correlated with Korean but not U.S. election outcomes.
This differential effect was found in trait judgments made by both Caucasian and
Korean participants. Interestingly, the faster the participants made face-based
trait inferences, the more strongly those inferences were correlated with real
election outcomes. These findings provide new insights into cultural effects and
the difficult question of causality underlying the association between facial
inferences and election outcomes. We also discuss the implications for political
science and cognitive psychology.
PMID- 28700648
TI - Highly diverse and antimicrobial susceptible Escherichia coli display a naive
bacterial population in fruit bats from the Republic of Congo.
AB - Bats are suspected to be a reservoir of several bacterial and viral pathogens
relevant to animal and human health, but studies on Escherichia coli in these
animals are sparse. We investigated the presence of E. coli in tissue samples
(liver, lung and intestines) collected from 50 fruit bats of five different
species (Eidolon helvum, Epomops franqueti, Hypsignathus monstrosus, Myonycteris
torquata, Rousettus aegyptiacus) of two different areas in the Republic of Congo
between 2009 and 2010. To assess E. coli pathotypes and phylogenetic
relationships, we determined the presence of 59 virulence associated genes and
multilocus sequence types (STs). Isolates were further tested for their
susceptibility to several antimicrobial substances by agar disk diffusion test
and for the presence of an Extended-Spectrum Beta-Lactamase phenotype. E. coli
was detected in 60% of the bats analysed. The diversity of E. coli strains was
very high, with 37 different STs within 40 isolates. Occasionally, we detected
sequence types (e.g. ST69, ST127, and ST131) and pathotypes (e.g. ExPEC, EPEC and
atypical EPEC), which are known pathogens in human and/or animal infections.
Although the majority of strains were assigned to phylogenetic group B2 (46.2%),
which is linked with the ExPEC pathovar, occurrence of virulence-associated genes
in these strains were unexpectedly low. Due to this, and as only few of the E.
coli isolates showed intermediate resistance to certain antimicrobial substances,
we assume a rather naive E. coli population, lacking contact to humans or
domestic animals. Future studies featuring in depth comparative whole genome
sequence analyses will provide insights into the microevolution of this
interesting strain collection.
PMID- 28700649
TI - Autophagy mediates cell cycle response by regulating nucleocytoplasmic transport
of PAX6 in limbal stem cells under ultraviolet-A stress.
AB - Limbal stem cells (LSC) account for homeostasis and regeneration of corneal
epithelium. Solar ultraviolet A (UVA) is the major source causing oxidative
damage in the ocular surface. Autophagy, a lysosomal degradation mechanism, is
essential for physiologic function and stress defense of stem cells. PAX6, a
master transcription factor governing corneal homeostasis by regulating cell
cycle and cell fate of LSC, responds to oxidative stress by nucleocytoplasmic
shuttling. Impaired autophagy and deregulated PAX6 have been reported in
oxidative stress-related ocular surface disorders. We hypothesize a functional
role for autophagy and PAX6 in LSC's stress response to UVA. Therefore, human LSC
colonies were irradiated with a sub-lethal dose of UVA and autophagic activity
and intracellular reactive oxygen species (ROS) were measured by CYTO-ID assay
and CM-H2DCFDA live staining, respectively. Following UVA irradiation, the
percentage of autophagic cells significantly increased in LSC colonies while
intracellular ROS levels remained unaffected. siRNA-mediated knockdown (KD) of
ATG7 abolished UVA-induced autophagy and led to an excessive accumulation of ROS.
Upon UVA exposure, LSCs displayed nuclear-to-cytoplasmic translocation of PAX6,
while ATG7KD or antioxidant pretreatment largely attenuated the intracellular
trafficking event. Immunofluorescence showing downregulation of proliferative
marker PCNA and induction of cell cycle regulator p21 indicates cell cycle arrest
in UVA-irradiated LSC. Abolishing autophagy, adenoviral-assisted restoration of
nuclear PAX6 or antioxidant pretreatment abrogated the UVA-induced cell cycle
arrest. Adenoviral expression of an ectopic PAX gene, PAX7, did not affect UVA
cell cycle response. Furthermore, knocking down PAX6 attenuated the cell cycle
progression of irradiated ATG7KD LSC by de-repressing p21 expression.
Collectively, our data suggest a crosstalk between autophagy and PAX6 in
regulating cell cycle response of ocular progenitors under UVA stress. Autophagy
deficiency leads to impaired intracellular trafficking of PAX6, perturbed redox
balance and uncurbed cell cycle progression in UVA-stressed LSCs. The coupling of
autophagic machinery and PAX6 in cell cycle regulation represents an attractive
therapeutic target for hyperproliferative ocular surface disorders associated
with solar radiation.
PMID- 28700650
TI - Sulforaphane enhances irradiation effects in terms of perturbed cell cycle
progression and increased DNA damage in pancreatic cancer cells.
AB - BACKGROUND: Sulforaphane (SFN), an herbal isothiocyanate enriched in cruciferous
vegetables like broccoli and cauliflower, has gained popularity for its antitumor
effects in cell lines such as pancreatic cancer. Antiproliferative as well as
radiosensitizing properties were reported for head and neck cancer but little is
known about its effects in pancreatic cancer cells in combination with
irradiation (RT). METHODS: In four established pancreatic cancer cell lines we
investigated clonogenic survival, analyzed cell cycle distribution and compared
DNA damage via flow cytometry and western blot after treatment with SFN and RT.
RESULTS: Both SFN and RT show a strong and dose dependent survival reduction in
clonogenic assays, an induction of a G2/M cell cycle arrest and an increase in
gammaH2AX protein level indicating DNA damage. Effects were more pronounced in
combined treatment and both cell cycle perturbation and DNA damage persisted for
a longer period than after SFN or RT alone. Moreover, SFN induced a loss of DNA
repair proteins Ku 70, Ku 80 and XRCC4. CONCLUSION: Our results suggest that
combination of SFN and RT exerts a more distinct DNA damage and growth inhibition
than each treatment alone. SFN seems to be a viable option to improve treatment
efficacy of chemoradiation with hopefully higher rates of secondary resectability
after neoadjuvant treatment for pancreatic cancer.
PMID- 28700651
TI - Metric-based vs peer-reviewed evaluation of a research output: Lesson learnt from
UK's national research assessment exercise.
AB - PURPOSE: There is a general inquisition regarding the monetary value of a
research output, as a substantial amount of funding in modern academia is
essentially awarded to good research presented in the form of journal articles,
conferences papers, performances, compositions, exhibitions, books and book
chapters etc., which, eventually leads to another question if the value varies
across different disciplines. Answers to these questions will not only assist
academics and researchers, but will also help higher education institutions
(HEIs) make informed decisions in their administrative and research policies.
DESIGN AND METHODOLOGY: To examine both the questions, we applied the United
Kingdom's recently concluded national research assessment exercise known as the
Research Excellence Framework (REF) 2014 as a case study. All the data for this
study is sourced from the openly available publications which arose from the
digital repositories of REF's results and HEFCE's funding allocations. FINDINGS:
A world leading output earns between L7504 and L14,639 per year within the REF
cycle, whereas an internationally excellent output earns between L1876 and L3659,
varying according to their area of research. Secondly, an investigation into the
impact rating of 25315 journal articles submitted in five areas of research by UK
HEIs and their awarded funding revealed a linear relationship between the
percentage of quartile-one journal publications and percentage of 4* outputs in
Clinical Medicine, Physics and Psychology/Psychiatry/Neuroscience UoAs, and no
relationship was found in the Classics and Anthropology/Development Studies UoAs,
due to the fact that most publications in the latter two disciplines are not
journal articles. PRACTICAL IMPLICATIONS: The findings provide an indication of
the monetary value of a research output, from the perspectives of government
funding for research, and also what makes a good output, i.e. whether a
relationship exists between good quality output and the source of its
publication. The findings may also influence future REF submission strategies in
HEIs and ascertain that the impact rating of the journals is not necessarily a
reflection of the quality of research in every discipline, and this may have a
significant influence on the future of scholarly communications in general.
ORIGINALITY: According to the author's knowledge, this is the first time an
investigation has estimated the monetary value of a good research output.
PMID- 28700652
TI - Anomalous diffusion and q-Weibull velocity distributions in epithelial cell
migration.
AB - In multicellular organisms, cell motility is central in all morphogenetic
processes, tissue maintenance, wound healing and immune surveillance. Hence, the
control of cell motion is a major demand in the creation of artificial tissues
and organs. Here, cell migration assays on plastic 2D surfaces involving normal
(MDCK) and tumoral (B16F10) epithelial cell lines were performed varying the
initial density of plated cells. Through time-lapse microscopy quantities such as
speed distributions, velocity autocorrelations and spatial correlations, as well
as the scaling of mean-squared displacements were determined. We find that these
cells exhibit anomalous diffusion with q-Weibull speed distributions that evolves
non-monotonically to a Maxwellian distribution as the initial density of plated
cells increases. Although short-ranged spatial velocity correlations mark the
formation of small cell clusters, the emergence of collective motion was not
observed. Finally, simulational results from a correlated random walk and the
Vicsek model of collective dynamics evidence that fluctuations in cell velocity
orientations are sufficient to produce q-Weibull speed distributions seen in our
migration assays.
PMID- 28700653
TI - Plasma bradykinin and early diabetic nephropathy lesions in type 1 diabetes
mellitus.
AB - OBJECTIVE: To examine the association of bradykinin and related peptides with the
development of diabetic nephropathy lesions in 243 participants with type 1
diabetes (T1D) from the Renin-Angiotensin System Study who, at baseline, were
normoalbuminuric, normotensive and had normal or increased glomerular filtration
rate (GFR). DESIGN: Plasma concentrations of bradykinin and related peptides were
measured at baseline by quantitative mass spectrometry. All participants were
randomly assigned at baseline to receive placebo, enalapril or losartan during
the 5 years between kidney biopsies. Kidney morphometric data were available from
kidney biopsies at baseline and after 5 years. Relationships of peptides with
changes in morphometric variables were assessed using multiple linear regression
after adjustment for age, sex, diabetes duration, HbA1c, mean arterial pressure,
treatment assignment and, for longitudinal analyses, baseline structure. RESULTS:
Baseline median albumin excretion rate of study participants was 5.0 MUg/min, and
mean GFR was 128 mL/min/1.73 m2. After multivariable adjustment, higher plasma
concentration of bradykinin (1-8) was associated with greater glomerular volume
(partial r = 0.191, P = 0.019) and total filtration surface area (partial r =
0.211, P = 0.010), and higher bradykinin (1-7) and hyp3-bradykinin (1-7) were
associated with lower cortical interstitial fractional volume (partial r =
0.189, P = 0.011; partial r = -0.164, P = 0.027 respectively). In longitudinal
analyses, higher bradykinin was associated with preservation of surface density
of the peripheral glomerular basement membrane (partial r = 0.162, P = 0.013),
and for participants randomized to losartan, higher hyp3-bradykinin (1-8) was
associated with more limited increase in cortical interstitial fractional volume
(partial r = -0.291, P = 0.033). CONCLUSIONS: Higher plasma bradykinin and
related peptide concentrations measured before clinical onset of diabetic
nephropathy in persons with T1D were associated with preservation of glomerular
structures, suggesting that elevations of these kinin concentrations may reflect
adaptive responses to early renal structural changes in diabetic nephropathy.
PMID- 28700654
TI - Body composition changes in male patients with chronic obstructive pulmonary
disease: Aging or disease process?
AB - BACKGROUND: Chronic obstructive pulmonary disease (COPD) mainly affects middle
age and elderly adults. It is unclear if the presence of muscle wasting and fat
accumulation in patients with COPD is age or disease-related. This study
investigated the effect of age and COPD disease severity on body composition with
the aim of identifying a biomarker(s) for COPD. METHODS: Healthy subjects and
patients with COPD of different severity were recruited. Dual-energy X-ray
absorptiometry was used to analyze total and segmental body composition. Subjects
included in the analysis were classified into four groups: healthy young (aged 20
45 years) (n = 35), healthy old (aged >= 60 years) (n = 37), moderate COPD (n =
40), and severe COPD (n = 14). RESULTS: In healthy old adults, leg and limb lean
masses were lower by 10.6% and 8.5%, respectively, compared with healthy young
adults (P < 0.05). Appendicular lean outcomes were significantly lower in the
moderate COPD compared to the healthy old group and were significant lower in
subjects with severe COPD compared to those with moderate COPD. All fat depots
were similar for both young and old healthy subjects and subjects with moderate
COPD, but significantly decreased in patients with severe COPD. CONCLUSIONS: This
study examined the changes in total and segmental body composition with aging and
COPD severity. It found that aging and COPD altered the body composition
differently, and the effect was most pronounced in leg lean mass. Remarkably,
differences in appendicular lean masses were seen in mild COPD although no
changes in body weight or BMI were apparent compared with healthy young adults.
In contrast, fat depot changes were only observed in severe COPD. Aging and COPD
processes are multifactorial and additional longitudinal studies are required to
explore both the quantitative and qualitative changes in body composition with
aging and disease process.
PMID- 28700655
TI - Cyclophosphamide leads to persistent deficits in physical performance and in vivo
mitochondria function in a mouse model of chemotherapy late effects.
AB - Fatigue is the symptom most commonly reported by long-term cancer survivors and
is increasingly recognized as related to skeletal muscle dysfunction. Traditional
chemotherapeutic agents can cause acute toxicities including cardiac and skeletal
myopathies. To investigate the mechanism by which chemotherapy may lead to
persistent skeletal muscle dysfunction, mature adult mice were injected with a
single cyclophosphamide dose and evaluated for 6 weeks. We found that exposed
mice developed a persistent decrease in treadmill running time compared to
baseline (25.7+/-10.6 vs. 49.0+/-16.8 min, P = 0.0012). Further, 6 weeks after
drug exposure, in vivo parameters of mitochondrial function remained below
baseline including maximum ATP production (482.1 +/- 48.6 vs. 696.2 +/- 76.6, P =
0.029) and phosphocreatine to ATP ratio (3.243 +/- 0.1 vs. 3.878 +/- 0.1, P =
0.004). Immunoblotting of homogenized muscles from treated animals demonstrated a
transient increase in HNE adducts 1 week after exposure that resolved by 6 weeks.
However, there was no evidence of an oxidative stress response as measured by
quantitation of SOD1, SOD2, and catalase protein levels. Examination of mtDNA
demonstrated that the mutation frequency remained comparable between control and
treated groups. Interestingly, there was evidence of a transient increase in NF
KB p65 protein 1 day after drug exposure as compared to saline controls (0.091+/
0.017 vs. 0.053+/-0.022, P = 0.033). These data suggest that continued impairment
in muscle and mitochondria function in cyclophosphamide-treated animals is not
linked to persistent oxidative stress and that alternative mechanisms need to be
considered.
PMID- 28700656
TI - Unexpected effects of azole transporter inhibitors on antifungal susceptibility
in Candida glabrata and other pathogenic Candida species.
AB - The pathogenic fungus Candida glabrata is often resistant to azole antifungal
agents. Drug efflux through azole transporters, such as Cdr1 and Cdr2, is a key
mechanism of azole resistance and these genes are under the control of the
transcription factor Pdr1. Recently, the monoamine oxidase A (MAO-A) inhibitor
clorgyline was shown to inhibit the azole efflux pumps, leading to increased
azole susceptibility in C. glabrata. In the present study, we have evaluated the
effects of clorgyline on susceptibility of C. glabrata to not only azoles, but
also to micafungin and amphotericin B, using wild-type and several mutant
strains. The addition of clorgyline to the culture media increased fluconazole
susceptibility of a C. glabrata wild-type strain, whereas micafungin and
amphotericin B susceptibilities were markedly decreased. These phenomena were
also observed in other medically important Candida species, including Candida
albicans, Candida parapsilosis, Candida tropicalis, and Candida krusei.
Expression levels of CDR1, CDR2 and PDR1 mRNAs and an amount of Cdr1 protein in
the C. glabrata wild-type strain were highly increased in response to the
treatment with clorgyline. However, loss of Cdr1, Cdr2, Pdr1, and a putative
clorgyline target (Fms1), which is an ortholog of human MAO-A, or overexpression
of CDR1 did not affect the decreased susceptibility to micafungin and
amphotericin B in the presence of clorgyline. The presence of other azole efflux
pump inhibitors including milbemycin A4 oxime and carbonyl cyanide 3
chlorophenylhydrazone also decreased micafungin susceptibility in C. glabrata
wild-type, Deltacdr1, Deltacdr2, and Deltapdr1 strains. These findings suggest
that azole efflux pump inhibitors increase azole susceptibility but concurrently
induce decreased susceptibility to other classes of antifungals independent of
azole transporter functions.
PMID- 28700657
TI - Increased transgene expression level of rabies virus vector for transsynaptic
tracing.
AB - Viral vectors that can infect neurons transsynaptically and can strongly express
foreign genes are useful for investigating the organization of neural circuits.
We previously developed a propagation-competent rabies virus (RV) vector based on
a highly attenuated HEP-Flury strain (rHEP5.0-CVSG), which selectively infects
neurons and propagates between synaptically connected neurons in a retrograde
direction. Its relatively low level of transgene expression, however, makes
immunostaining necessary to visualize the morphological features of infected
neurons. To increase the transgene expression level of this RV vector, in this
study we focused on two viral proteins: the large protein (L) and matrix protein
(M). We first attempted to enhance the expression of L, which is a viral RNA
polymerase, by deleting the extra transcription unit and shortening the
intergenic region between the G and L genes. This viral vector (rHEP5.0-GctL)
showed increased transgene expression level with efficient transsynaptic
transport. We next constructed an RV vector with a rearranged gene order (rHEP5.0
GML) with the aim to suppress the expression of M, which plays a regulatory role
in virus RNA synthesis. Although this vector showed high transgene expression
level, the efficiency of transsynaptic transport was low. To further evaluate the
usability of rHEP5.0-GctL as a transsynaptic tracer, we inserted a fluorescent
timer as a transgene, which changes the color of its fluorescence from blue to
red over time. This viral vector enabled us the differentiation of primary
infected neurons from secondary infected neurons in terms of the fluorescence
wavelength. We expect this propagation-competent RV vector to be useful for
elucidating the complex organization of the central nervous system.
PMID- 28700658
TI - Nanosecond electric pulses differentially affect inward and outward currents in
patch clamped adrenal chromaffin cells.
AB - This study examined the effect of 5 ns electric pulses on macroscopic ionic
currents in whole-cell voltage-clamped adrenal chromaffin cells. Current-voltage
(I-V) relationships first established that the early peak inward current was
primarily composed of a fast voltage-dependent Na+ current (INa), whereas the
late outward current was composed of at least three ionic currents: a voltage
gated Ca2+ current (ICa), a Ca2+-activated K+ current (IK(Ca)), and a sustained
voltage-dependent delayed rectifier K+ current (IKV). A constant-voltage step
protocol was next used to monitor peak inward and late outward currents before
and after cell exposure to a 5 ns pulse. A single pulse applied at an electric
(E)-field amplitude of 5 MV/m resulted in an instantaneous decrease of ~4% in
peak INa that then declined exponentially to a level that was ~85% of the initial
level after 10 min. Increasing the E-field amplitude to 8 or 10 MV/m caused a
twofold greater inhibitory effect on peak INa. The decrease in INa was not due to
a change in either the steady-state inactivation or activation of the Na+ channel
but instead was associated with a decrease in maximal Na+ conductance. Late
outward current was not affected by a pulse applied at 5 MV/m. However, for a
pulse applied at the higher E-field amplitudes of 8 and 10 MV/m, late outward
current in some cells underwent a progressive ~22% decline over the course of the
first 20 s following pulse exposure, with no further decline. The effect was most
likely concentrated on ICa and IK(Ca) as IKV was not affected. The results of
this study indicate that in whole-cell patch clamped adrenal chromaffin cells, a
5 ns pulse differentially inhibits specific voltage-gated ionic currents in a
manner that can be manipulated by tuning E-field amplitude.
PMID- 28700659
TI - Expression levels of cleaved caspase-3 and caspase-3 in tumorigenesis and
prognosis of oral tongue squamous cell carcinoma.
AB - Apoptosis plays a dual role in cancer development and malignancy. The role of
apoptosis-related caspases in cancer remains controversial, particularly in oral
tongue squamous cell carcinoma (OTSCC). In this study, we examined the protein
levels of cleaved caspase-3, caspase-3, caspase-8, and caspase-9 on tissue
microarrays consisting of samples from 246 OTSCC patients by
immunohistochemistry. Wilcoxon signed-rank test indicated that the protein levels
of cleaved caspase-3, caspase-3, caspase-8, and caspase-9 in tumor tissues were
significantly higher compared to those in adjacent normal tissues (all p<0.001).
The expression level of caspase-8 in tumors was elevated in patients with lymph
node invasion. Moreover, positive expression of cleaved caspase-3 was associated
with shorter disease-free survival (DFS) in OTSCC patients with moderate
differentiation and lymph node invasion. Combination of either positive cleaved
caspase-3 or higher caspase-3 expression or both was associated with poor DFS.
Interestingly, stratification analysis showed that co-expression levels of
positive cleaved caspase-3 or/and higher caspase-3 were associated with better
disease-specific survival in patients with advanced stages of the disease, such
as large tumor size and lymph node invasion, whereas it was associated with poor
DFS in OTSCC patients with moderate cell differentiation and small tumor size.
Taken together, cleaved caspase-3 and caspase-3/8/9 could be biomarkers for
tumorigenesis in OTSCC patients. The co-expression level of cleaved caspase-3 and
caspase-3 might be a prognostic biomarker for OTSCC patients, particular in those
patients with certain tumor stages and cell differentiation status.
PMID- 28700660
TI - Cancer-selective, single agent chemoradiosensitising gold nanoparticles.
AB - Two nanometre gold nanoparticles (AuNPs), bearing sugar moieties and/or thiol
polyethylene glycol-amine (PEG-amine), were synthesised and evaluated for their
in vitro toxicity and ability to radiosensitise cells with 220 kV and 6 MV X
rays, using four cell lines representing normal and cancerous skin and breast
tissues. Acute 3 h exposure of cells to AuNPs, bearing PEG-amine only or a 50:50
ratio of alpha-galactose derivative and PEG-amine resulted in selective uptake
and toxicity towards cancer cells at unprecedentedly low nanomolar
concentrations. Chemotoxicity was prevented by co-administration of N-acetyl
cysteine antioxidant, or partially prevented by the caspase inhibitor Z-VAD-FMK.
In addition to their intrinsic cancer-selective chemotoxicity, these AuNPs acted
as radiosensitisers in combination with 220 kV or 6 MV X-rays. The ability of
AuNPs bearing simple ligands to act as cancer-selective chemoradiosensitisers at
low concentrations is a novel discovery that holds great promise in developing
low-cost cancer nanotherapeutics.
PMID- 28700661
TI - Highly sensitive sandwich immunoassay and immunochromatographic test for the
detection of Clostridial epsilon toxin in complex matrices.
AB - Epsilon toxin is one of the four major toxins of Clostridium perfringens. It is
the third most potent clostridial toxin after botulinum and tetanus toxins and is
thus considered as a potential biological weapon classified as category B by the
Centers for Disease Control and Prevention (CDC). In the case of a bioterrorist
attack, there will be a need for a rapid, sensitive and specific detection method
to monitor food and water contamination by this toxin, and for a simple human
diagnostic test. We have produced and characterized five monoclonal antibodies
against common epitopes of epsilon toxin and prototoxin. Three of them neutralize
the cytotoxic effects of epsilon toxin in vitro. With these antibodies, we have
developed highly sensitive tests, overnight and 4-h sandwich enzyme immunoassays
and an immunochromatographic test performed in 20 min, reaching detection limits
of at least 5 pg/mL (0.15 pM), 30 pg/mL (0.9 pM) and 100 pg/mL (3.5 pM) in
buffer, respectively. These tests were also evaluated for detection of epsilon
toxin in different matrices: milk and tap water for biological threat detection,
serum, stool and intestinal content for human or veterinary diagnostic purposes.
Detection limits in these complex matrices were at least 5-fold better than those
described in the literature (around 1 to 5 ng/mL), reaching 10 to 300 pg/mL using
the enzyme immunoassay and 100 to 2000 pg/mL using the immunochromatographic
test.
PMID- 28700662
TI - BRG1 promotes hepatocarcinogenesis by regulating proliferation and invasiveness.
AB - The chromatin remodeler complex SWI/SNF plays an important role in physiological
and pathological processes. Brahma related gene 1(BRG1), a catalytic subunit of
the SWI/SNF complex, is known to be mutated in hepatocellular carcinoma (HCC).
However, its role in HCC remains unclear. Here, we investigate the role of BRG1
on cell growth and invasiveness as well as its effect on the expression of
putative target genes. Expression of BRG1 was examined in human liver tissue
samples and in HCC cell lines. In addition, BRG1 was silenced in human HCC cell
lines to analyse cell growth and invasiveness by growth curves, colony formation
assay, invasion assay and the expression of putative target genes. BRG1 was found
to be significantly increased in HCC samples compared to non-HCC samples. In
addition, a declined proliferation rate of BRG1-silenced human HCC cell lines was
associated with a decrease of expression of cyclin family members. In line with a
decreased invasiveness of BRG1-siRNA-treated human HCC cell lines, down
regulation of MMP7 was detected. These results support the hypothesis that
overexpression of BRG1 increases cell growth and invasiveness in HCC.
Furthermore, the data highlight cyclin B, E and MMP7 to be associated with BRG1
during hepatocarcinogenesis.
PMID- 28700663
TI - Predictors and long-term health outcomes of eating disorders.
AB - Anorexia and bulimia nervosa may have long-term effects on overall and
reproductive health. We studied predictors of self-reported eating disorders and
associations with later health events. We estimated odds ratios (ORs) for these
associations in 47,759 participants from the Sister Study. Two percent (n = 967)
of participants reported a history of an eating disorder. Risk factors included
being non-Hispanic white, having well-educated parents, recent birth cohort (OR =
2.16, 95% confidence interval [CI]: 2.01-2.32 per decade), and having a sister
with an eating disorder (OR = 3.68, CI: 1.92-7.02). As adults, women who had
experienced eating disorders were more likely to smoke, to be underweight, to
have had depression, to have had a later first birth, to have experienced
bleeding or nausea during pregnancy, or to have had a miscarriage or induced
abortion. In this descriptive analysis, we identified predictors of and possible
long-term health consequences of eating disorders. Eating disorders may have
become more common over time. Interventions should focus on prevention and
mitigation of long-term adverse health effects.
PMID- 28700664
TI - Systematic screening for skin, hair, and nail abnormalities in a large-scale
knockout mouse program.
AB - The International Knockout Mouse Consortium was formed in 2007 to inactivate
("knockout") all protein-coding genes in the mouse genome in embryonic stem
cells. Production and characterization of these mice, now underway, has generated
and phenotyped 3,100 strains with knockout alleles. Skin and adnexa diseases are
best defined at the gross clinical level and by histopathology. Representative
retired breeders had skin collected from the back, abdomen, eyelids, muzzle,
ears, tail, and lower limbs including the nails. To date, 169 novel mutant lines
were reviewed and of these, only one was found to have a relatively minor
sebaceous gland abnormality associated with follicular dystrophy. The B6N(Cg)
Far2tm2b(KOMP)Wtsi/2J strain, had lesions affecting sebaceous glands with what
appeared to be a secondary follicular dystrophy. A second line, B6N(Cg)
Ppp1r9btm1.1(KOMP)Vlcg/J, had follicular dystrophy limited to many but not all
mystacial vibrissae in heterozygous but not homozygous mutant mice, suggesting
that this was a nonspecific background lesion. We discuss potential reasons for
the low frequency of skin and adnexal phenotypes in mice from this project in
comparison to those seen in human Mendelian diseases, and suggest alternative
approaches to identification of human disease-relevant models.
PMID- 28700665
TI - Solution conformations of Zika NS2B-NS3pro and its inhibition by natural products
from edible plants.
AB - The recent Zika viral (ZIKV) epidemic has been associated with severe
neurological pathologies such as neonatal microcephaly and Guillain-Barre
syndrome but unfortunately no vaccine or medication is effectively available yet.
Zika NS2B-NS3pro is essential for the proteolysis of the viral polyprotein and
thereby viral replication. Thus NS2B-NS3pro represents an attractive target for
anti-Zika drug discovery/design. Here, we have characterized the solution
conformations and catalytic parameters of both linked and unlinked Zika NS2B
NS3pro complexes and found that the unlinked complex manifested well-dispersed
NMR spectra. Subsequently with selective isotope-labeling using NMR spectroscopy,
we demonstrated that C-terminal residues (R73-K100) of NS2B is highly disordered
without any stable tertiary and secondary structures in the Zika NS2B-NS3pro
complex in the free state. Upon binding to the well-characterized serine protease
inhibitor, bovine pancreatic trypsin inhibitor (BPTI), only the extreme C
terminal residues (L86-K100) remain disordered. Additionally, we have identified
five flavonoids and one natural phenol rich in edible plants including fruits and
vegetables, which inhibit Zika NS2B-NS3pro in a non-competitive mode, with Ki
ranging from 770 nM for Myricetin to 34.02 MUM for Apigenin. Molecular docking
showed that they all bind to a pocket on the back of the active site and their
structure-activity relationship was elucidated. Our study provides valuable
insights into the solution conformation of Zika NS2B-NS3pro and further deciphers
its susceptibility towards allosteric inhibition by natural products. As these
natural product inhibitors fundamentally differ from the currently-known active
site inhibitors in terms of both inhibitory mode and chemical scaffold, our
finding might open a new avenue for development of better allosteric inhibitors
to fight ZIKV infection.
PMID- 28700666
TI - Effects of Kluyveromyces marxianus supplementation on immune responses,
intestinal structure and microbiota in broiler chickens.
AB - To investigate the effects of Kluyveromyces marxianus on immune responses,
intestinal structure and microbiota in broilers, 840 1-d-old broiler chicks were
randomly divided into seven groups (eight replicates) and were fed basal diets
without or with 0.25, 0.50, 1.0, 1.5, 2.0, and 2.5 g/kg of K. marxianus (2.0*1010
CFU/g). Serum and intestine samples were collected at 21 d of age. The results
showed that increasing K. marxianus addition linearly reduced feed conversion
ratio but linearly elevated relative thymus weight, as well as quadratically
increased serum lysozyme and IgG levels, with the medium dose (1.0 g/kg) being
the most effective. The ratio of villus height to crypt depth of jejunum and
ileum, ileal villus height and sucrase activity, as well as the mRNA expression
of ileal mucin-2, claudin-1 and sodium glucose cotransporter 1 linearly responded
to the increasing K. marxianus addition. Supplemental K. marxianus at low (0.5
g/kg), medium (1.5 g/kg) and high (2.5 g/kg) dose all decreased the abundance of
phylum Cyanobacteria, increased the abundance of phylum Firmicutes and genus
Lactobacillus in ileum. The high dose of K. marxianus addition also reduced the
abundance of order Rickettsiales and Pseudomonadales along with species
Acinetobacter junii. Ileal bacterial communities between K. marxianus-treated and
untreated groups formed distinctly different clusters. In summary, K. marxianus
supplementation benefits feed efficiency and immune function, as well as
intestinal structure in broilers, which might be attributed to the improved ileal
microbial structure. Supplemental K. marxianus at high dose (2.5 g/kg) was more
effective for feed efficiency and intestinal health of broilers, while the innate
immunity was optimized at a medium dose (1.0 g/kg).
PMID- 28700667
TI - Age-dependent differential regulation of anxiety- and depression-related
behaviors by neurabin and spinophilin.
AB - Affective disorders impact nearly 10% of the adult population in the United
States in a given year. Synaptic dysfunction has recently emerged as a key
neurobiological mechanism underlying affective disorders such as anxiety and
depression. In this study, we investigate the potential role of two synaptic
scaffolding proteins, neurabin and spinophilin, in regulating anxiety- and
depression-related behaviors at different ages using genetically deficient mice.
Loss of the neurabin gene reduces anxiety-like behavior in the elevated zero maze
in young adult mice (3-5 months old), but not in middle aged mice (11-13 months
old), whereas loss of spinophilin decreases anxiety in middle-aged mice, but not
in young adult mice. Neurabin knockout (KO) mice also show reduced immobility in
the repeated force swim test (FST) at 3-5 months, but not 11-3 months, of age,
compared to age- and strain-matched wild type (WT) controls. Conversely,
spinophilin KO mice display a lower level of this behavioral despair than matched
WT controls after repeated FST trials at the middle age (11-13 months) but not
the young age (3-5 months). Together, these data indicate that, despite their
structural similarities and overlapping function in regulating synaptic
cytoskeleton, the two homologs neurabin and spinophilin play important yet
distinct roles in the regulation of anxiety- and depression-like behaviors in an
age-dependent manner. Our studies provide new insights into the complex
neurobiology of affective disorders.
PMID- 28700668
TI - Conditional cell reprogramming involves non-canonical beta-catenin activation and
mTOR-mediated inactivation of Akt.
AB - The combination of irradiated fibroblast feeder cells and Rho kinase inhibitor, Y
267362, converts primary epithelial cells growing in vitro into an
undifferentiated adult stem cell-like state that is characterized by long-term
proliferation. This cell culture method also maintains the proliferation of adult
epithelial stem cells from various tissues. Both primary and adult stem cells
retain their tissue-specific differentiation potential upon removal of the
culture conditions. Due to the ability to modulate the proliferation and
differentiation of the cells, this method is referred to as conditional
reprogramming and it is increasingly being used in studies of tumor
heterogeneity, personalized medicine and regenerative medicine. However, little
is known about the biology of these conditionally reprogrammed (CR) cells.
Previously we showed that beta-catenin activation, a hallmark of stem cells in
vivo, occurs in CR human ectocervical cells (HECs). Here we show that beta
catenin-dependent transcription is necessary for the induction of epithelial stem
cell markers, and that beta-catenin is activated via a non-canonical pathway that
is independent of Wnt and Akt/GSK-3. Active Akt actually decreases due to
increased mTOR signaling, with a consequent increase in dephosphorylated, active
GSK-3. Despite the increase in active GSK-3, beta-catenin associates with protein
phosphatase 2A (PP2A) and is activated. Inhibition of PP2A catalytic activity
reduces both the level of active beta-catenin and the acute induction of stem
cell markers, suggesting an important role for PP2A in the activation of beta
catenin. Moreover, we demonstrate similar results using human prostate and breast
cells, indicating that these changes are not restricted to ectocervical
epithelial cells and may represent a more fundamental property of conditional
reprogramming.
PMID- 28700669
TI - Long term health outcomes in patients with a history of myocardial infarction: A
population based cohort study.
AB - BACKGROUND: Myocardial infarction (MI) is associated with high morbidity and
mortality, particularly in the first 12 months post-event. Interventions such as
dual antiplatelet therapy can reduce the risk of major adverse cardiovascular
events (MACE), but the duration of the high-risk time interval and the optimal
prescription time frame for these interventions remains unknown. DESIGN, SETTING,
PARTICIPANTS, AND MEASUREMENTS: We performed a retrospective cohort study using
data from medical services and hospitalizations in Manitoba, Canada for patients
admitted with a MI between April 2006 and March 2010, and followed until Nov 30,
2014. We used survival analysis to determine the cumulative incidence of death,
subsequent MI, or stroke, and used Cox proportional hazards models to assess
factors associated with these endpoints. RESULTS: There were 8,493 patients in
Manitoba admitted to hospital for a MI during the study period. Of those, 6,749
(79.5%) survived for at least 1 year without a recurrent MI or stroke. In the
following year, this population remained at high risk, with 372 (5.5%) of the
remaining patients dying in the next twelve months (48.1% cardiovascular deaths),
244 (3.6%) having a recurrent MI, and 74 (1.1%) having a stroke. Older age, male
sex, diabetes, prior stroke, prior heart failure, prior unstable angina, and
absence of revascularization were associated with worse long-term prognosis.
CONCLUSIONS: The risk of MACE remains elevated among post-MI patients after the
first year. Interventions to more intensively monitor, evaluate, and treat these
patients should be considered beyond the first year following myocardial
infarction.
PMID- 28700670
TI - Taurine does not affect the composition, diversity, or metabolism of human
colonic microbiota simulated in a single-batch fermentation system.
AB - Accumulating evidence suggests that dietary taurine (2-aminoethanesulfonic acid)
exerts beneficial anti-inflammatory effects in the large intestine. In this
study, we investigated the possible impact of taurine on human colonic microbiota
using our single-batch fermentation system (Kobe University Human Intestinal
Microbiota Model; KUHIMM). Fecal samples from eight humans were individually
cultivated with and without taurine in the KUHIMM. The results showed that
taurine remained largely undegraded after 30 h of culturing in the absence of
oxygen, although some 83% of the taurine was degraded after 30 h of culturing
under aerobic conditions. Diversity in bacterial species in the cultures was
analyzed by 16S rRNA gene sequencing, revealing that taurine caused no
significant change in the diversity of the microbiota; both operational taxonomic
unit and Shannon-Wiener index of the cultures were comparable to those of the
respective source fecal samples. In addition, principal coordinate analysis
indicated that taurine did not alter the composition of bacterial species, since
the 16S rRNA gene profile of bacterial species in the original fecal sample was
maintained in each of the cultures with and without taurine. Furthermore,
metabolomic analysis revealed that taurine did not affect the composition of
short-chain fatty acids produced in the cultures. These results, under these
controlled but artificial conditions, suggested that the beneficial anti
inflammatory effects of dietary taurine in the large intestine are independent of
the intestinal microbiota. We infer that dietary taurine may act directly in the
large intestine to exert anti-inflammatory effects.
PMID- 28700671
TI - A case-control study on association of proteasome subunit beta 8 (PSMB8) and
transporter associated with antigen processing 1 (TAP1) polymorphisms and their
transcript levels in vitiligo from Gujarat.
AB - BACKGROUND: Autoimmunity has been implicated in the destruction of melanocytes
from vitiligo skin. Major histocompatibility complex (MHC) class-II linked genes
proteasome subunit beta 8 (PSMB8) and transporter associated with antigen
processing 1 (TAP1), involved in antigen processing and presentation have been
reported to be associated with several autoimmune diseases including vitiligo.
OBJECTIVES: To explore PSMB8 rs2071464 and TAP1 rs1135216 single nucleotide
polymorphisms and to estimate the expression of PSMB8 and TAP1 in patients with
vitiligo and unaffected controls from Gujarat. METHODS: PSMB8 rs2071464
polymorphism was genotyped using polymerase chain reaction- restriction fragment
length polymorphism (PCR-RFLP) and TAP1 rs1135216 polymorphism was genotyped by
amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) in
378 patients with vitiligo and 509 controls. Transcript levels of PSMB8 and TAP1
were measured in the PBMCs of 91 patients and 96 controls by using qPCR. Protein
levels of PSMB8 were also determined by Western blot analysis. RESULTS: The
frequency of 'TT' genotype of PSMB8 polymorphism was significantly lowered in
patients with generalized and active vitiligo (p = 0.019 and p = 0.005) as
compared to controls suggesting its association with the activity of the disease.
However, TAP1 polymorphism was not associated with vitiligo susceptibility. A
significant decrease in expression of PSMB8 at both transcript level (p = 0.002)
as well as protein level (p = 0.0460) was observed in vitiligo patients as
compared to controls. No significant difference was observed between patients and
controls for TAP1 transcripts (p = 0.553). Interestingly, individuals with the
susceptible CC genotype of PSMB8 polymorphism showed significantly reduced PSMB8
transcript level as compared to that of CT and TT genotypes (p = 0.009 and p =
0.003 respectively). CONCLUSIONS: PSMB8 rs2071464 was associated with generalized
and active vitiligo from Gujarat whereas TAP1 rs1135216 showed no association.
The down-regulation of PSMB8 in patients with risk genotype 'CC' advocates the
vital role of PSMB8 in the autoimmune basis of vitiligo.
PMID- 28700672
TI - Prediction of clinical depression scores and detection of changes in whole-brain
using resting-state functional MRI data with partial least squares regression.
AB - In diagnostic applications of statistical machine learning methods to brain
imaging data, common problems include data high-dimensionality and co-linearity,
which often cause over-fitting and instability. To overcome these problems, we
applied partial least squares (PLS) regression to resting-state functional
magnetic resonance imaging (rs-fMRI) data, creating a low-dimensional
representation that relates symptoms to brain activity and that predicts clinical
measures. Our experimental results, based upon data from clinically depressed
patients and healthy controls, demonstrated that PLS and its kernel variants
provided significantly better prediction of clinical measures than ordinary
linear regression. Subsequent classification using predicted clinical scores
distinguished depressed patients from healthy controls with 80% accuracy.
Moreover, loading vectors for latent variables enabled us to identify brain
regions relevant to depression, including the default mode network, the right
superior frontal gyrus, and the superior motor area.
PMID- 28700673
TI - The trickle-down effect of predictability: Secondary task performance benefits
from predictability in the primary task.
AB - Predictions optimize processing by reducing attentional resources allocation to
expected or predictable sensory data. Our study demonstrates that these saved
processing resources can be then used on concurrent stimuli, and in consequence
improve their processing and encoding. We illustrate this "trickle-down" effect
with a dual task, where the primary task varied in terms of predictability. The
primary task involved detection of a pre-specified symbol that appeared at some
point of a short video of a dot moving along a random, semi-predictable or
predictable trajectory. The concurrent secondary task involved memorization of
photographs representing either emotionally neutral or non-neutral (social or
threatening) content. Performance in the secondary task was measured by a memory
test. We found that participants allocated more attention to unpredictable
(random and semi-predictable) stimuli than to predictable stimuli. Additionally,
when the stimuli in the primary task were more predictable, participants
performed better in the secondary task, as evidenced by higher sensitivity in the
memory test. Finally, social or threatening stimuli were allocated more "looking
time" and a larger number of saccades than neutral stimuli. This effect was
stronger for the threatening stimuli than social stimuli. Thus, predictability of
environmental input is used in optimizing the allocation of attentional
resources, which trickles-down and benefits the processing of concurrent stimuli.
PMID- 28700674
TI - Effects of taurine on resting-state fMRI activity in spontaneously hypertensive
rats.
AB - Attention deficit hyperactivity disorder (ADHD) is a global behavior illness
among children and adults. To investigate the effects of taurine on resting-state
fMRI activity in ADHD, a spontaneously hypertensive rat (SHR) animal model was
adopted. Significantly decreased serum C-reactive protein (CRP) was detected in
rats of Wistar Kyoto (WKY) high-taurine group and significantly decreased
interleukin (IL)-1beta and CRP were detected in rats of SHR low-taurine and high
taurine groups. Moreover, significantly higher horizontal locomotion was detected
in rats of WKY low-taurine and SHR low-taurine groups than in those of controls.
In contrast, significantly lower horizontal locomotion was detected in rats of
the SHR high-taurine group than in those of the SHR control group. Additionally,
significantly lower functional connectivity (FC) and mean amplitude of low
frequency fluctuation (mALFF) in the bilateral hippocampus in rats of WKY high
taurine and SHR high-taurine groups was detected. Notably, the mALFF in rats of
the SHR low-taurine and high-taurine groups was significantly lower than in those
of the SHR control group. These findings suggest that the administration of a
high-dose taurine probably improves hyperactive behavior in SHR rats by
ameliorating the inflammatory cytokines and modulating brain functional signals
in SHR rats.
PMID- 28700675
TI - Occupation with grain crops is associated with lower type 1 diabetes incidence:
Registry-based case-control study.
AB - Intranasal administration of gliadin prevents autoimmune diabetes in non-obese
diabetic mice. The current study was designed to investigate if bakers are
intranasally exposed to gluten during work and whether occupation as baker is
inversely associated with type 1 diabetes. Gliadin was measured in nasal swabs
from eight bakers and butchers. The odds ratio of type 1 diabetes in selected
profession groups was analysed in a registry-based case-control study with data
from 1980 to 2010 derived from Statistics Denmark. The cohort included 1,210,017
Danish individuals, thereof 15,451 with type 1 diabetes (1.28%). Average nasal
gliadin swab content after full working days was 6.3 MUg (confidence interval
(CI): 2.8 to 9.7) among bakers, while no nasal gliadin was detected among
butchers. The odds ratio of type 1 diabetes was lower among bakers (OR = 0.57;
CI: 0.52 to 0.62) and agriculture workers occupied with production of grains (OR
= 0.65; CI: 0.56 to 0.75). Bakers had a lower odds ratio of type 1 diabetes,
which potentially could be attributed to exposure of nasal mucosal gluten during
work, as observed in this study. If other studies confirm the present
observations, intranasal gliadin administration could possibly be an easy and
safe approach for the prevention of type 1 diabetes in high-risk individuals or
prediabetic subjects.
PMID- 28700676
TI - Imaging features of intracerebral hemorrhage with cerebral amyloid angiopathy:
Systematic review and meta-analysis.
AB - BACKGROUND: We sought to summarize Computed Tomography (CT)/Magnetic Resonance
Imaging (MRI) features of intracerebral hemorrhage (ICH) associated with cerebral
amyloid angiopathy (CAA) in published observational radio-pathological studies.
METHODS: In November 2016, two authors searched OVID Medline (1946-), Embase
(1974-) and relevant bibliographies for studies of imaging features of lobar or
cerebellar ICH with pathologically proven CAA ("CAA-associated ICH"). Two authors
assessed studies' diagnostic test accuracy methodology and independently
extracted data. RESULTS: We identified 22 studies (21 cases series and one cross
sectional study with controls) of CT features in 297 adults, two cross-sectional
studies of MRI features in 81 adults and one study which reported both CT and MRI
features in 22 adults. Methods of CAA assessment varied, and rating of imaging
features was not masked to pathology. The most frequently reported CT features of
CAA-associated ICH in 21 case series were: subarachnoid extension (pooled
proportion 82%, 95% CI 69-93%, I2 = 51%, 12 studies) and an irregular ICH border
(64%, 95% CI 32-91%, I2 = 85%, five studies). CAA-associated ICH was more likely
to be multiple on CT than non-CAA ICH in one cross-sectional study (CAA
associated ICH 7/41 vs. non-CAA ICH 0/42; chi2 = 7.8, p = 0.005). Superficial
siderosis on MRI was present in 52% of CAA-associated ICH (95% CI 39-65%, I2 =
35%, 3 studies). CONCLUSIONS: Subarachnoid extension and an irregular ICH border
are common imaging features of CAA-associated ICH, but methodologically rigorous
diagnostic test accuracy studies are required to determine the sensitivity and
specificity of these features.
PMID- 28700677
TI - Human adenovirus type 5 vectors deleted of early region 1 (E1) undergo limited
expression of early replicative E2 proteins and DNA replication in non-permissive
cells.
AB - Adenovirus (Ad) vectors deleted of the early region 1 (E1) are widely used for
transgene delivery in preclinical and clinical gene therapy studies. Although
proteins encoded within the E1 region are required for efficient virus
replication, previous studies have suggested that certain viral or cellular
proteins can functionally compensate for E1, leading to expression of the early
region 2 (E2)-encoded replicative proteins and subsequent virus replication. We
have generated a series of E1-encoding and E1-deficient Ad vectors containing a
FLAG-epitope tag on each of the E2-encoded proteins: DNA-binding protein (DBP),
terminal protein (TP) and DNA polymerase (Pol). Using these constructs, we show
that for the replication-competent virus, the expression level of each E2-encoded
protein declines with increasing distance from the E2 promoter, with E2A-encoded
DBP expression being ~800-fold higher than E2B-encoded TP. Pol was expressed at
extremely low levels in infected cells, and immunoprecipitation from cell lysates
was required prior to its detection by immunoblot. We further show that DBP was
expressed 200- to 400-fold less efficiently from an E1-deficient virus compared
to a replication-competent virus in A549 and HepG2 cells, which was accompanied
by a very small increase in genome copy number. For the E1-deficient virus, late
gene expression (a marker of virus replication) was only observed at very high
multiplicities of infection. These data show that E1-deleted Ad gives rise to
limited expression of the E2-encoded genes and replication in infected cells, but
highlight the importance of considering viral dose-dependent effects in gene
therapy studies.
PMID- 28700678
TI - Correction: Production of IL-8, VEGF and Elastase by Circulating and Intraplaque
Neutrophils in Patients with Carotid Atherosclerosis.
AB - [This corrects the article DOI: 10.1371/journal.pone.0124565.].
PMID- 28700679
TI - Aged-associated cytomegalovirus and Epstein-Barr virus reactivation and
cytomegalovirus relationship with the frailty syndrome in older women.
AB - Immunosenescence is an age-related reduction of immune system activity that can
be associated with frailty. This study aimed to compare cytomegalovirus (CMV) and
Epstein-Barr virus (EBV) reactivations (based on viremias) between young and
elderly women who had a chronic CMV and/or EBV infection (i.e., an IgG+
serostatus) without an acute infection (i.e., an IgM- serostatus), and among the
elderly group categorized according to frailty status. DNA was extracted from
plasma using standard protocols and serostatus was determined by enzyme-linked
immunosorbent assay. Quantitative real-time polymerase chain reaction analyses
for CMV and EBV were carried out and viral loads were determined. Among elderly
women (n = 71), 59% were positive for CMV, in contrast to only 8% of young women
(n = 73). Elderly women classified as frail, pre-frail, and non-frail presented
82%, 56%, and 48% positivity for CMV, respectively. Frequency and viral load were
significantly higher in the elderly group vs. the young group (p < 0.0001 and p =
0.01, respectively) and in elderly with frailty vs. those without frailty (p =
0.007 and p = 0.03, respectively). The frequency of CMV reactivation presented
odds ratios of 11.77 for aging and 6.13 for frailty, and relative risks of 5.39
for aging and 1.93 for frailty. EBV was detected in 30% of the elderly women and
15% of the young women (p = 0.04); however, the viral load did not significantly
differ between the two age groups. The frequency of EBV reactivation presented
odds ratios of 2.36 for aging and 2.90 for frailty, and relative risks of 1.96
for aging and 2.12 for frailty. However, no difference in EBV viral load among
the frailty status subgroups was found. In conclusion, the frequency of CMV
reactivation was associated with aging and ongoing frailty, whereas the frequency
of EBV reactivation was associated only with aging.
PMID- 28700680
TI - The role of treatment timing and mode of stimulation in the treatment of primary
dysmenorrhea with acupuncture: An exploratory randomised controlled trial.
AB - OBJECTIVES: We examined the effect of changing treatment timing and the use of
manual, electro acupuncture on the symptoms of primary dysmenorrhea. METHODS: A
randomised controlled trial was performed with four arms, low frequency manual
acupuncture (LF-MA), high frequency manual acupuncture (HF-MA), low frequency
electro acupuncture (LF-EA) and high frequency electro acupuncture (HF-EA). A
manualised trial protocol was used to allow differentiation and individualized
treatment over three months. A total of 74 women were randomly assigned to one of
the four groups (LF-MA n = 19, HF-MA n = 18, LF-EA n = 18, HF-EA n = 19). Twelve
treatments were performed over three menstrual cycles, either once per week (LF
groups) or three times in the week prior to menses (HF groups). All groups
received a treatment in the first 48 hours of menses. The primary outcome was the
reduction in peak menstrual pain at 12 months from trial entry. RESULTS: During
the treatment period and nine month follow-up all groups showed statistically
significant (p < .001) reductions in peak and average menstrual pain compared to
baseline but there were no differences between groups (p > 0.05). Health related
quality of life increased significantly in six domains in groups having high
frequency of treatment compared to two domains in low frequency groups. Manual
acupuncture groups required less analgesic medication than electro-acupuncture
groups (p = 0.02). HF-MA was most effective in reducing secondary menstrual
symptoms compared to both-EA groups (p<0.05). CONCLUSION: Acupuncture treatment
reduced menstrual pain intensity and duration after three months of treatment and
this was sustained for up to one year after trial entry. The effect of changing
mode of stimulation or frequency of treatment on menstrual pain was not
significant. This may be due to a lack of power. The role of acupuncture
stimulation on menstrual pain needs to be investigated in appropriately powered
randomised controlled trials.
PMID- 28700681
TI - Correction: Seminal plasma induces inflammation and enhances HIV-1 replication in
human cervical tissue explants.
AB - [This corrects the article DOI: 10.1371/journal.ppat.1006402.].
PMID- 28700682
TI - Circumscription of the genus Lepra, a recently resurrected genus to accommodate
the "Variolaria"-group of Pertusaria sensu lato (Pertusariales, Ascomycota).
AB - Pertusarialean lichens include more than 300 species belonging to several
independent phylogenetic lineages. Only some of these phylogenetic clades have
been comprehensively sampled for molecular data, and formally described as
genera. Here we present a taxonomic treatment of a group of pertusarialean
lichens formerly known as "Pertusaria amara-group", "Monomurata-group", or
"Variolaria-group", which includes widespread and well-known taxa such as P.
amara, P. albescens, or P. ophthalmiza. We generated a 6-locus data set with 79
OTUs representing 75 species. The distinction of the Variolaria clade is
supported and consequently, the resurrection of the genus Lepra is followed.
Thirty-five new combinations into Lepra are proposed and the new species Lepra
austropacifica is described from mangroves in the South Pacific. Lepra is
circumscribed to include species with disciform ascomata, a weakly to non-amyloid
hymenial gel, strongly amyloid asci without clear apical amyloid structures,
containing 1 or 2, single-layered, thin-walled ascospores. Chlorinated xanthones
are not present, but thamnolic and picrolichenic acids occur frequently, as well
as orcinol depsides. Seventy-one species are accepted in the genus. Although the
distinction of the genus from Pertusaria is strongly supported, the relationships
of Lepra remain unresolved and the genus is tentatively placed in Pertusariales
incertae sedis.
PMID- 28700683
TI - Correction: Central Presynaptic Terminals Are Enriched in ATP but the Majority
Lack Mitochondria.
AB - [This corrects the article DOI: 10.1371/journal.pone.0125185.].
PMID- 28700684
TI - Turns with multiple and single head cast mediate Drosophila larval light
avoidance.
AB - Drosophila larvae exhibit klinotaxis when placed in a gradient of temperature,
chemicals, or light. The larva samples environmental stimuli by casting its head
from side to side. By comparing the results of two consecutive samples, it
decides the direction of movement, appearing as a turn proceeded by one or more
head casts. Here by analyzing larval behavior in a light-spot-based phototaxis
assay, we showed that, in addition to turns with a single cast (1-cast), turns
with multiple head casts (n-cast) helped to improve the success of light
avoidance. Upon entering the light spot, the probability of escape from light
after the first head cast was only ~30%. As the number of head casts increased,
the chance of successful light avoidance increased and the overall chance of
escaping from light increased to >70%. The amplitudes of first head casts that
failed in light avoidance were significantly smaller in n-cast turns than those
in 1-cast events, indicating that n-cast turns might be planned before completion
of the first head cast. In n-casts, the amplitude of the second head cast was
generally larger than that of the first head cast, suggesting that larvae tried
harder in later attempts to improve the efficacy of light avoidance. We propose
that both 1-cast turns and n-cast turns contribute to successful larval light
avoidance, and both can be initiated at the first head cast.
PMID- 28700685
TI - Characterization of the molecular chaperone ClpB from the pathogenic spirochaete
Leptospira interrogans.
AB - Leptospira interrogans is a spirochaete responsible for leptospirosis in mammals.
The molecular mechanisms of the Leptospira virulence remain mostly unknown.
Recently, it has been demonstrated that an AAA+ chaperone ClpB (a member of the
Hsp100 family) from L. interrogans (ClpBLi) is not only essential for survival of
Leptospira under the thermal and oxidative stresses, but also during infection of
a host. The aim of this study was to provide further insight into the role of
ClpB in the pathogenic spirochaetes and explore its biochemical properties. We
found that a non-hydrolysable ATP analogue, ATPgammaS, but not AMP-PNP induces
the formation of ClpBLi hexamers and stabilizes the associated form of the
chaperone. ADP also induces structural changes in ClpBLi and promotes its self
assembly, but does not produce full association into the hexamers. We also
demonstrated that ClpBLi exhibits a weak ATPase activity that is stimulated by
kappa-casein and poly-lysine, and may mediate protein disaggregation
independently from the DnaK chaperone system. Unexpectedly, the presence of E.
coli DnaK/DnaJ/GrpE did not significantly affect the disaggregation activity of
ClpBLi and ClpBLi did not substitute for the ClpBEc function in the clpB-null E.
coli strain. This result underscores the species-specificity of the ClpB
cooperation with the co-chaperones and is most likely due to a loss of
interactions between the ClpBLi middle domain and the E. coli DnaK. We also found
that ClpBLi interacts more efficiently with the aggregated G6PDH in the presence
of ATPgammaS rather than ATP. Our results indicate that ClpB's importance during
infection might be due to its role as a molecular chaperone involved in
reactivation of protein aggregates.
PMID- 28700686
TI - Renin inhibition improves metabolic syndrome, and reduces angiotensin II levels
and oxidative stress in visceral fat tissues in fructose-fed rats.
AB - Renin-angiotensin system in visceral fat plays a crucial role in the pathogenesis
of metabolic syndrome in fructose-fed rats. However, the effects of renin
inhibition on visceral adiposity in metabolic syndrome are not fully
investigated. We investigated the effects of renin inhibition on visceral
adiposity in fructose-fed rats. Male Wistar-Kyoto rats were divided into 4 groups
for 8-week experiments: Group Con (standard chow diet), Group Fru (high-fructose
diet; 60% fructose), Group FruA (high-fructose diet and concurrent aliskiren
treatment; 100 mg/kg body weight [BW] per day), and Group FruB (high-fructose
diet and subsequent, i.e. 4 weeks after initiating high-fructose feeding,
aliskiren treatment; 100 mg/kg BW per day). The high-fructose diet induced
metabolic syndrome, increased visceral fat weights and adipocyte sizes, and
augmented angiotensin II (Ang II), NADPH oxidase (NOX) isoforms expressions,
oxidative stress, and dysregulated production of adipocytokines from visceral
adipose tissues. Concurrent and subsequent aliskiren administration ameliorated
metabolic syndrome, dysregulated adipocytokines, and visceral adiposity in high
fructose-fed hypertensive rats, and was associated with reducing Ang II levels,
NOX isoforms expressions and oxidative stress in visceral fat tissues. Therefore,
this study demonstrates renin inhibition could improve metabolic syndrome, and
reduce Ang II levels and oxidative stress in visceral fat tissue in fructose-fed
rats, and suggests that visceral adipose Ang II plays a crucial role in the
pathogenesis of metabolic syndrome in fructose-fed rats.
PMID- 28700687
TI - Secretory carrier membrane protein 5 is an autophagy inhibitor that promotes the
secretion of alpha-synuclein via exosome.
AB - Autophagy-lysosomal pathway is a cellular protective system to remove aggregated
proteins and damaged organelles. Meanwhile, exosome secretion has emerged as a
mode to selectively clear the neurotoxic proteins, such as alpha-synuclein.
Mounting evidence suggests that these two cellular processes are coordinated to
facilitate the clearance of toxic cellular waste; however the regulators for the
transition between these two processes are unclear. Here we show that SCAMP5, a
secretory carrier membrane protein significantly induced in the brains of
Huntington's disease patients, is quickly and transiently induced by protein
stress and autophagic stimulation, and is regulated by the master autophagy
transcriptional regulator TFEB. Ironically, SCAMP5 inhibits autophagy flux by
blocking the fusion of autophagosomes and lysosomes. Although autophagy is
blocked, SCAMP5 does not cause significant protein aggregation in cells. Instead,
it promotes the Golgi fragmentation and stimulates the unconventional secretion
of the co-localizing alpha-synuclein via exosome as an exosome component.
Therefore, we have identified SCAMP5 as a novel coordinator of autophagy and
exosome secretion, which is induced upon protein stress to channel the efficient
clearance of toxic proteins via the exosomes rather than autophagy-lysosomal
pathway.
PMID- 28700689
TI - Correction: E6 and E7 Gene Polymorphisms in Human Papillomavirus Types-58 and 33
Identified in Southwest China.
AB - [This corrects the article DOI: 10.1371/journal.pone.0171140.].
PMID- 28700688
TI - Four simple rules that are sufficient to generate the mammalian blastocyst.
AB - Early mammalian development is both highly regulative and self-organizing. It
involves the interplay of cell position, predetermined gene regulatory networks,
and environmental interactions to generate the physical arrangement of the
blastocyst with precise timing. However, this process occurs in the absence of
maternal information and in the presence of transcriptional stochasticity. How
does the preimplantation embryo ensure robust, reproducible development in this
context? It utilizes a versatile toolbox that includes complex intracellular
networks coupled to cell-cell communication, segregation by differential
adhesion, and apoptosis. Here, we ask whether a minimal set of developmental
rules based on this toolbox is sufficient for successful blastocyst development,
and to what extent these rules can explain mutant and experimental phenotypes. We
implemented experimentally reported mechanisms for polarity, cell-cell signaling,
adhesion, and apoptosis as a set of developmental rules in an agent-based in
silico model of physically interacting cells. We find that this model
quantitatively reproduces specific mutant phenotypes and provides an explanation
for the emergence of heterogeneity without requiring any initial transcriptional
variation. It also suggests that a fixed time point for the cells' competence of
fibroblast growth factor (FGF)/extracellular signal-regulated kinase (ERK) sets
an embryonic clock that enables certain scaling phenomena, a concept that we
evaluate quantitatively by manipulating embryos in vitro. Based on these
observations, we conclude that the minimal set of rules enables the embryo to
experiment with stochastic gene expression and could provide the robustness
necessary for the evolutionary diversification of the preimplantation gene
regulatory network.
PMID- 28700690
TI - Inactivation of human DGAT2 by oxidative stress on cysteine residues.
AB - Diacylglycerol acyltransferases (DGATs) have a crucial role in the biosynthesis
of triacylglycerol (TG), the major storage form of metabolic energy in eukaryotic
organisms. Even though DGAT2, one of two distinct DGATs, has a vital role in TG
biosynthesis, little is known about the regulation of DGAT2 activity. In this
study, we examined the role of cysteine and its oxidation in the enzymatic
activity of human DGAT2 in vitro. Human DGAT2 activity was considerably inhibited
not only by thiol-modifying reagents (NEM and IA) but also by ROS-related
chemicals (H2O2 and beta-lapachone), while human DGAT1 and GPAT1 were little
affected. Particularly, ROS-related chemicals concomitantly induced
intermolecular disulfide crosslinking of human DGAT2. Both the oxidative
inactivation and disulfide crosslinking were almost completely reversed by the
treatment with DTT, a disulfide-reducing agent. These results clearly
demonstrated the significant role of ROS-induced intermolecular crosslinking in
the inactivation of human DGAT2 and also suggested DGAT2 as a redox-sensitive
regulator in TG biosynthesis.
PMID- 28700691
TI - Rheumatoid arthritis is associated with rs17337023 polymorphism and increased
serum level of the EGFR protein.
AB - OBJECTIVE: We have previously described the association of rheumatoid arthritis
(RA) prevalence and two epidermal growth factor receptor (EGFR) SNPs (rs17337023
and rs2227983) among the Taiwanese population. This present study aimed to
elucidate whether the SNPs can alter the expression of EGFR in the progression of
RA. METHODS: The cohort study included 366 Taiwan's Han Chinese RA patients and
326 age and gender matched healthy controls. Blood samples collected from the
participants were analyzed to determine their serum EGFR levels and to identify
EGFR SNPs from their genomic DNA. Genotyping for EGFR SNPs was performed by
restriction fragment length polymorphism (RFLP) assay. The relationship between
EGFR SNP and the clinical manifestations of RA was evaluated. RESULTS: Our
results showed that a statistically significant difference in genotype frequency
distributions at rs17337023 SNP for RA patients and controls (p ? 0.05). In
addition, compared with the haplotype frequencies between case and control
groups, the RA patient with the GT haplotype appeared to be a significant
"protective" haplotype compared with other haplotypes (OR: 0.73, 95% CI: 0.59
0.91; p = 0.005). Furthermore, the increased serum level of EGFR was also
observed in RA patients (p ? 0.001). CONCLUSION: Our study showed that RA is
associated with rs17337023 SNP in EGFR gene and increased serum level of the EGFR
protein. These findings suggest EGFR is worthy of further investigation as a
therapeutic target for RA.
PMID- 28700692
TI - Gallic acid/hydroxypropyl-beta-cyclodextrin complex: Improving solubility for
application on in vitro/ in vivo Candida albicans biofilms.
AB - The aim of this study was to increase the solubility of gallic acid (GA) for the
treatment of Candida albicans biofilm, which is very difficult to treat and
requires high drug concentrations. Cyclodextrins (CDs) were used for this
purpose. Complexes were evaluated by phase-solubility studies, prepared by spray
drying and characterized by drug loading, scanning electron microscopy (SEM) and
differential scanning calorimetry (DSC). The complexes were tested on C. albicans
biofilm using in vitro and in vivo models. HPbetaCD formed soluble inclusion
complexes with GA. The percentage of GA in GA/HPbetaCD was 10.8 +/- 0.01%. The
SEM and DSC analyses confirmed the formation of inclusion complexes. GA/HPbetaCD
maintained the antimicrobial activity of the pure GA. GA/HPbetaCD was effective
on C. albicans biofilms of 24 and 48h. The in vivo results showed an anti
inflammatory activity of GA/HPbetaCD with no difference in invading hypha
counting among the groups. This study encourages the development of new
antifungal agents.
PMID- 28700693
TI - Risk factors for delayed antiretroviral therapy initiation among HIV-seropositive
patients.
AB - Prompt initiation of combination antiretroviral therapy (ART) is important to
reduce comorbidity and mortality among people living with HIV, especially for
those with a low CD4 cell count. However there is evidence that not everyone
receives prompt initiation of ART after enrolling into HIV care. The current
study investigated factors associated with failure to initiate ART within two
years of entering into care among those with a CD4 count at or below 350
cells/mm3. The sample included 4,907 ART-naive patients with a CD4 count at or
below 350 cells/mm3 enrolled between January 1, 2003 and December 31, 2012 at any
of eight clinical sites in the Center for AIDS Research Network of Integrated
Clinical Systems (CNICS). The two-year risk of delayed ART initiation was
estimated using a log-binomial regression model with stabilized inverse
probability of censoring weights for those lost to follow-up. Adjusting for other
factors, an earlier enrollment date was the sole demographic characteristic
associated with an increased risk of delayed ART initiation. Higher CD4 count,
lower viral load, and a prevalent AIDS diagnosis were clinical characteristics
associated with delayed ART initiation. Gender, age, race/ethnicity and HIV risk
factors such as reported male-to-male sexual contact and injection drug use were
not associated with delayed ART initiation. This study identified characteristics
of patients for whom treatment was strongly to moderately recommended but who did
not initiate ART within two years of entering care. Despite the known benefits of
early antiretroviral therapy initiation, a lower viral load measurement may
continue to be an important clinical characteristic in the more recent era with
current ART initiation guidelines. These findings provide a target for closer
monitoring and intervention to reduce disparities in HIV care.
PMID- 28700694
TI - A robust and efficient method for the extraction of plant extracellular surface
lipids as applied to the analysis of silks and seedling leaves of maize.
AB - Aerial plant organs possess a diverse array of extracellular surface lipids,
including both non-polar and amphipathic constituents that collectively provide a
primary line of defense against environmental stressors. Extracellular surface
lipids on the stigmatic silks of maize are composed primarily of saturated and
unsaturated linear hydrocarbons, as well as fatty acids, and aldehydes. To
efficiently extract lipids of differing polarities from maize silks, five solvent
systems (hexanes; hexanes:diethyl ether (95:5); hexanes:diethyl ether (90:10);
chloroform:hexanes (1:1) and chloroform) were tested by immersing fresh silks in
solvent for different extraction times. Surface lipid recovery and the relative
composition of individual constituents were impacted to varying degrees depending
on solvent choice and duration of extraction. Analyses were performed using both
silks and leaves to demonstrate the utility of the solvent- and time-optimized
protocol in comparison to extraction with the commonly used chloroform solvent.
Overall, the preferred solvent system was identified as hexanes:diethyl ether
(90:10), based on its effectiveness in extracting surface hydrocarbons and fatty
acids as well as its reduced propensity to extract presumed internal fatty acids.
Metabolite profiling of wildtype and glossy1 seedlings, which are impaired in
surface lipid biosynthesis, demonstrated the ability of the preferred solvent to
extract extracellular surface lipids rich in amphipathic compounds (aldehydes and
alcohols). In addition to the expected deficiencies in dotriacontanal and
dotriacontan-1-ol for gl1 seedlings, an unexpected increase in fatty acid
recovery was observed in gl1 seedlings extracted in chloroform, suggesting that
chloroform extracts lipids from internal tissues of gl1 seedlings. This
highlights the importance of extraction method when evaluating mutants that have
altered cuticular lipid compositions. Finally, metabolite profiling of silks from
maize inbreds B73 and Mo17, exposed to different environments and harvested at
different ages, revealed differences in hydrocarbon and fatty acid composition,
demonstrating the dynamic nature of surface lipid accumulation on silks.
PMID- 28700695
TI - Does practicing a wide range of joint angle configurations lead to higher
flexibility in a manual obstacle-avoidance target-pointing task?
AB - Flexibility in motor actions can be defined as variability in the use of degrees
of freedom (e.g., joint angles in the arm) over repetitions while keeping
performance (e.g., fingertip position) stabilized. We examined whether
flexibility can be increased through enlarging the joint angle range during
practice in a manual obstacle-avoidance target-pointing task. To establish
differences in flexibility we partitioned the variability in joint angles over
repetitions in variability within (GEV) and variability outside the solution
space (NGEV). More GEV than NGEV reflects flexibility; when the ratio of the GEV
and NGEV is higher, flexibility is higher. The pretest and posttest consisted of
30 repetitions of manual pointing to a target while moving over a 10 cm high
obstacle. To enlarge the joint angle range during practice participants performed
600 target-pointing movements while moving over obstacles of different heights (5
9 cm, 11-15 cm). The results indicated that practicing movements over obstacles
of different heights led participants to use enlarged range of joint angles
compared to the range of joint angles used in movements over the 10 cm obstacle
in the pretest. However, for each individual obstacle neither joint angle
variance nor flexibility were higher during practice. We also did not find more
flexibility after practice. In the posttest, joint angle variance was in fact
smaller than before practice, primarily in GEV. The potential influences of
learning effects and the task used that could underlie the results obtained are
discussed. We conclude that with this specific type of practice in this specific
task, enlarging the range of joint angles does not lead to more flexibility.
PMID- 28700696
TI - Small-molecule inhibition of pyruvate phosphate dikinase targeting the nucleotide
binding site.
AB - Pyruvate phosphate dikinase (PPDK) is an essential enzyme of C4 photosynthesis in
plants, catalyzing the ATP-driven conversion of pyruvate to phosphoenolpyruvate
(PEP). It is further used by some bacteria and unicellular protists in the
reverse, ATP-forming direction. Many weed species use C4 photosynthesis in
contrast to world's major crops, which are C3 plants. Hence inhibitors of PPDK
may be used as C4-specific herbicides. By screening a library of 80 commercially
available kinase inhibitors, we identified compounds derived from
bisindolylmaleimide (bisindolylmaleimide IV, IC50 = 0.76 +/- 0.13 MUM) and
indirubin (indirubin-3'-monoxime, IC50 = 4.2 +/- 0.9 MUM) that showed high
inhibitory potency towards PPDK and are among the most effective PPDK inhibitors
described today. Physiological studies on leaf tissues of a C4 model plant
confirmed in vivo inhibition of C4-driven photosynthesis by these substances.
Moreover, comparative docking studies of non-inhibitory bisindolylmaleimide
derivatives suggest that the selectivity towards PPDK may be increased by
addition of functional groups to the core structure.
PMID- 28700697
TI - Simulating the origins of life: The dual role of RNA replicases as an obstacle to
evolution.
AB - Despite years of study, it is still not clear how life emerged from inanimate
matter and evolved into the complex forms that we observe today. One of the most
recognized hypotheses for the origins of life, the RNA World hypothesis, assumes
that life was sparked by prebiotic replicating RNA chains. In this paper, we
address the problems caused by the interplay between hypothetical prebiotic RNA
replicases and RNA parasitic species. We consider the coexistence of parasite
RNAs and RNA replicases as well as the impact of parasites on the further
evolution of replicases. For these purposes, we used multi-agent modeling
techniques that allow for realistic assumptions regarding the movement and
spatial interactions of modeled species. The general model used in this study is
based on work by Takeuchi and Hogeweg. Our results confirm that the coexistence
of parasite RNAs and replicases is possible in a spatially extended system, even
if we take into consideration more realistic assumptions than Takeuchi and
Hogeweg. However, we also showed that the presence of trade-off that takes into
the account an RNA folding process could still pose a serious obstacle to the
evolution of replication. We conclude that this might be a cause for one of the
greatest transitions in life that took place early in evolution-the separation of
the function between DNA templates and protein enzymes, with a central role for
RNA species.
PMID- 28700698
TI - Suppressors of selection.
AB - Inspired by recent works on evolutionary graph theory, an area of growing
interest in mathematical and computational biology, we present examples of
undirected structures acting as suppressors of selection for any fitness value r
> 1. This means that the average fixation probability of an advantageous mutant
or invader individual placed at some node is strictly less than that of this
individual placed in a well-mixed population. This leads the way to study more
robust structures less prone to invasion, contrary to what happens with the
amplifiers of selection where the fixation probability is increased on average
for advantageous invader individuals. A few families of amplifiers are known,
although some effort was required to prove it. Here, we use computer aided
techniques to find an exact analytical expression of the fixation probability for
some graphs of small order (equal to 6, 8 and 10) proving that selection is
effectively reduced for r > 1. Some numerical experiments using Monte Carlo
methods are also performed for larger graphs and some variants.
PMID- 28700699
TI - Smoking during pregnancy in relation to grandchild birth weight and BMI
trajectories.
AB - BACKGROUND: Maternal smoking has been linked to lower birth weight and higher
risk of childhood obesity. However, it is unknown whether grand-maternal smoking
during pregnancy is associated with grandchildren birth weight and body mass
index (BMI) trajectories. METHODS: We investigated associations of smoking during
pregnancy with birth weight, risks of overweight and BMI trajectories among
46,858 mother-child dyads and 6,583 grandmother-mother-child triads of three
cohort studies of related individuals. Smoking during pregnancy was reported by
mothers, and anthropometric data were provided by participants in each cohort.
RESULTS: Compared to grandchildren of non-smoking women, grandchildren of women
who smoked more than 14 cigarettes per day throughout pregnancy were 70 g (95%
CI: 12, 129 g; P for trend = 0.01) heavier at birth, and 18% (95% CI: 4%, 34%; P
for trend = 0.01) more likely to become overweight. The mean BMI of grandchildren
of women who smoked during pregnancy was 0.45 kg/m2 (95% CI: 0.14, 0.75 kg/m2; P
for trend = 0.006) higher through adolescence and young adulthood than that of
grandchildren of non-smoking mothers. CONCLUSIONS: Grandmothers' smoking during
pregnancy was associated with higher birth weight, higher risk of overweight, and
higher BMI through adolescence and young adulthood.
PMID- 28700700
TI - The induction of the transcription factor Nrf2 enhances the antinociceptive
effects of delta-opioid receptors in diabetic mice.
AB - The involvement of heme oxygenase 1 (HO-1) in the modulation of the
antinociceptive effects of opioids in type 1 diabetes has been demonstrated but
the role played by the transcription factor Nrf2 in the regulation of painful
neuropathy and in the effects and expression of delta-opioid receptors (DOR) in
type 2 diabetes, has not been studied. In male BKS.Cg-m+/+Leprdb/J (db/db) mice,
the anti-allodynic effects produced by a Nrf2 transcription factor activator,
sulforaphane (SFN) administered alone and combined with two DOR agonists, [d
Pen(2),d-Pen(5)]-Enkephalin (DPDPE) and (+)-4-[(alphaR)-alpha-((2S,5R)-4-Allyl
2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]-N,N diethylbenzamide (SNC-80), were
evaluated. The effects of SFN on glucose levels and body weight as well as on the
proteins levels of Nrf2, HO-1, NAD(P)H: quinone oxidoreductase 1 (NQO1), MAPKs
(JNK) and DOR in sciatic nerve from db/db mice were also assessed. This study
showed that the administration of SFN dose dependently reversed mechanical
allodynia, reduced hyperglycemia and body weight gain associated to type 2
diabetes and significantly increased the anti-allodynic effects of DPDPE and SNC
80 in db/db mice. This treatment normalized the down regulation of Nrf2 and NQO1
and enhanced the protein levels of HO-1 in db/db mice. Moreover, the
administration of SFN also inhibited the JNK phosphorylation and DOR down
regulation in the sciatic nerve of diabetic mice. Our data indicated that SFN
treatment is effective in reversing mechanical allodynia and enhancing DOR
antinociceptive effects in db/db mice which effects might be mediated by
activating Nrf2 signaling, reducing hyperglycemia, inhibiting JNK phosphorylation
and avoiding DOR down-regulation in the sciatic nerve of these animals. These
results propose SFN, alone and/or combined with DOR agonists, as interesting
approaches for the treatment of painful diabetic neuropathy associated to type 2
diabetes in mice.
PMID- 28700701
TI - Development and validation of the Maugeri Sleep Quality and Distress Inventory
(MaSQuDI-17).
AB - OBJECTIVES: The aim of this study was to develop and validate a questionnaire
designed to measure the impact of sleep impairment on emotional distress in
patients with various sleep disorders. METHODS: Five experts created an item data
bank pertaining to sleep-related psychological symptoms and somatic perceptions.
Fifty patients in two focus groups examined each item for: a) word clarity
(indicating any ambiguity of interpretation) and b) appropriateness for the
target population. This process permitted to identify 36 appropriate items.
Classical Test Theory and Rasch Analysis were used to further refine the
questionnaire, yielding the final 17-item set. Concurrent validation of the new
scale was tested with the Pittsburgh Sleep Quality Index, Epworth Sleepiness
Scale, and the Anxiety and Depression questionnaires. RESULTS: Starting from the
initial item data-bank, a 17-item questionnaire, the Maugeri Sleep Quality and
Distress Inventory (MaSQuDI-17), was produced. Parallel Analysis on the MaSQuDI
17 confirmed the presence of a single dimension; exploratory factor analysis
showed salient loading for each item, explaining 58.7% of total variance. Item
remainder correlation ranged from 0.72 to 0.39 and Cronbach alpha was 0.896.
Rasch analysis revealed satisfactory psychometric properties of the new scale:
the rating structure performed according to expectations, model fit was good and
no item dependencies emerged. The scale presented good convergent validity and
scores significantly distinguished healthy subjects from OSAS or Insomnia or BSD
(p < 0.001). CONCLUSIONS: MaSQuDI -17 shows good psychometric qualities, and can
be used to assess the impact of sleep disorders such as Insomnia, OSAS, Central
Hypersomnia and BSD on emotional stress.
PMID- 28700702
TI - You are fair, but I expect you to also behave unfairly: Positive asymmetry in
trait-behavior relations for moderate morality information.
AB - Trait inference in person perception is based on observers' implicit assumptions
about the relations between trait adjectives (e.g., fair) and the either
consistent or inconsistent behaviors (e.g., having double standards) that an
actor can manifest. This article presents new empirical data and theoretical
interpretations on people' behavioral expectations, that is, people's perceived
trait-behavior relations along the morality (versus competence) dimension. We
specifically address the issue of the moderate levels of both traits and
behaviors almost neglected by prior research by using a measure of the perceived
general frequency of behaviors. A preliminary study identifies a set of
competence- and morality-related traits and a subset of traits balanced for
valence. Studies 1-2 show that moral target persons are associated with greater
behavioral flexibility than immoral ones where abstract categories of behaviors
are concerned. For example, participants judge it more likely that a fair person
would behave unfairly than an unfair person would behave fairly. Study 3
replicates the results of the first 2 studies using concrete categories of
behaviors (e.g., telling the truth/omitting some information). Study 4 shows that
the positive asymmetry in morality-related trait-behavior relations holds for
both North-American and European (i.e., Italian) individuals. A small-scale meta
analysis confirms the existence of a positive asymmetry in trait-behavior
relations along both morality and competence dimensions for moderate levels of
both traits and behaviors. We discuss these findings in relation to prior models
and results on trait-behavior relations and we advance a motivational explanation
based on self-protection.
PMID- 28700703
TI - Correction: Measurement of macular structure-function relationships using
spectral domain-optical coherence tomography (SD-OCT) and pattern
electroretinograms (PERG).
AB - [This corrects the article DOI: 10.1371/journal.pone.0178004.].
PMID- 28700704
TI - Screening for the protective effect target of deproteinized extract of calf blood
and its mechanisms in mice with CCl4-induced acute liver injury.
AB - Liver injury is a common pathological basis of various liver diseases, and long
term liver injury is often an important initiation factor leading to liver
fibrosis and even liver cirrhosis and hepatocellular carcinoma (HCC). It has been
reported that deproteinized extract of calf blood (DECB) can inhibit the
replication of hepatitis B virus and confers a protective effect on the liver
after traumatic liver injury. However, few studies on the regulatory factors and
mechanisms of DECB have been reported. In this current study, an acute mouse
liver injury model was established with carbon tetrachloride (CCl4). The
differentially expressed genes and related cell signal transduction pathways were
screened using mRNA expression microarray. STEM software V1.3.6 was used for
clustering gene functions, and the DAVID and KEGG databases were applied for the
analysis. A total of 1355 differentially expressed genes were selected, among
which nine were validated by RT-qPCR. The results showed that the Fas, IL1b,
Pik3r1, Pik3r5, Traf2, Traf2, Csf2rb2, Map3k14, Pik3cd and Ppp3cc genes were
involved in the regulation of DECB in an acute mouse liver injury model. Targets
of the protective effects of DECB and its related mechanisms were found in mice
with acute liver injury induced by carbon tetrachloride, which may provide an
important theoretical basis for further DECB research.
PMID- 28700705
TI - Cumulative effects of prenatal-exposure to exogenous chemicals and psychosocial
stress on fetal growth: Systematic-review of the human and animal evidence.
AB - BACKGROUND: Adverse effects of prenatal stress or environmental chemical
exposures on fetal growth are well described, yet their combined effect remains
unclear. OBJECTIVES: To conduct a systematic review on the combined impact and
interaction of prenatal exposure to stress and chemicals on developmental
outcomes. METHODS: We used the first three steps of the Navigation Guide
systematic review. We wrote a protocol, performed a robust literature search to
identify relevant animal and human studies and extracted data on developmental
outcomes. For the most common outcome (fetal growth), we evaluated risk of bias,
calculated effect sizes for main effects of individual and combined exposures,
and performed a random effects meta-analysis of those studies reporting on odds
of low birthweight (LBW) by smoking and socioeconomic status (SES). RESULTS: We
identified 17 human- and 22 animal-studies of combined chemical and stress
exposures and fetal growth. Human studies tended to have a lower risk of bias
across nine domains. Generally, we found stronger effects for chemicals than
stress, and these exposures were associated with reduced fetal growth in the low
stress group and the association was often greater in high stress groups, with
limited evidence of effect modification. We found smoking associated with
significantly increased odds of LBW, with a greater effect for high stress (low
SES; OR 4.75 (2.46-9.16)) compared to low stress (high SES; OR 1.95 (95% CI 1.53
2.48)). Animal studies generally had a high risk of bias with no significant
combined effect or effect modification. CONCLUSIONS: We found that despite
concern for the combined effects of environmental chemicals and stress, this is
still an under-studied topic, though limited available human studies indicate
chemical exposures exert stronger effects than stress, and this effect is
generally larger in the presence of stress.
PMID- 28700706
TI - Spatial distribution of cannabinoid receptor type 1 (CB1) in normal canine
central and peripheral nervous system.
AB - The endocannabinoid system is a regulatory pathway consisting of two main types
of cannabinoid receptors (CB1 and CB2) and their endogenous ligands, the
endocannabinoids. The CB1 receptor is highly expressed in the central and
peripheral nervous systems (PNS) in mammalians and is involved in neuromodulatory
functions. Since endocannabinoids were shown to be elevated in cerebrospinal
fluid of epileptic dogs, knowledge about the species specific CB receptor
expression in the nervous system is required. Therefore, we assessed the spatial
distribution of CB1 receptors in the normal canine CNS and PNS.
Immunohistochemistry of several regions of the brain, spinal cord and peripheral
nerves from a healthy four-week-old puppy, three six-month-old dogs, and one ten
year-old dog revealed strong dot-like immunoreactivity in the neuropil of the
cerebral cortex, Cornu Ammonis (CA) and dentate gyrus of the hippocampus,
midbrain, cerebellum, medulla oblongata and grey matter of the spinal cord. Dense
CB1 expression was found in fibres of the globus pallidus and substantia nigra
surrounding immunonegative neurons. Astrocytes were constantly positive in all
examined regions. CB1 labelled neurons and satellite cells of the dorsal root
ganglia, and myelinating Schwann cells in the PNS. These results demonstrate for
the first time the spatial distribution of CB1 receptors in the healthy canine
CNS and PNS. These results can be used as a basis for further studies aiming to
elucidate the physiological consequences of this particular anatomical and
cellular distribution.
PMID- 28700707
TI - Environmental bacteriophages active on biofilms and planktonic forms of toxigenic
Vibrio cholerae: Potential relevance in cholera epidemiology.
AB - METHODS: Phages isolated from environmental waters in Bangladesh were tested for
their host specificity towards V. cholerae O1 and O139, and the ability to
disperse V. cholerae biofilms formed in the laboratory. Representative phages
were further characterized by electron microscopy and whole genome sequencing.
Selected phages were then introduced in various combinations to biofilms of
toxigenic V. cholerae added to samples of river water, and the dispersion of
biofilms as well as the growth kinetics of V. cholerae and the phages were
monitored. RESULTS: A phage cocktail composed of three different phages isolated
from surface waters in Bangladesh and designated as JSF7, JSF4, and JSF3 could
significantly influence the distribution and concentration of the active
planktonic form and biofilm associated form of toxigenic V. cholerae in water.
While JSF7 showed a biofilm degrading activity and dispersed cells from both V.
cholerae O1 and O139 derived biofilms thus increasing the concentration of
planktonic V. cholerae in water, JSF4 and JSF3 showed strong bactericidal
activity against V. cholerae O1 and O139 respectively. A mixture of all three
phages could effectively reduce both biofilm-associated and planktonic V.
cholerae in river water microcosms. SIGNIFICANCE: Besides potential applicability
in phage-mediated control of cholera, our results have relevance in appreciating
possible intricate role of diverse environmental phages in the epidemiology of
the disease, since both biofilms and phages influence the prevalence and
infectivity of V. cholerae in a variety of ways.
PMID- 28700708
TI - Lower extremity EMG-driven modeling of walking with automated adjustment of
musculoskeletal geometry.
AB - Neuromusculoskeletal disorders affecting walking ability are often difficult to
manage, in part due to limited understanding of how a patient's lower extremity
muscle excitations contribute to the patient's lower extremity joint moments. To
assist in the study of these disorders, researchers have developed
electromyography (EMG) driven neuromusculoskeletal models utilizing scaled
generic musculoskeletal geometry. While these models can predict individual
muscle contributions to lower extremity joint moments during walking, the
accuracy of the predictions can be hindered by errors in the scaled geometry.
This study presents a novel EMG-driven modeling method that automatically adjusts
surrogate representations of the patient's musculoskeletal geometry to improve
prediction of lower extremity joint moments during walking. In addition to
commonly adjusted neuromusculoskeletal model parameters, the proposed method
adjusts model parameters defining muscle-tendon lengths, velocities, and moment
arms. We evaluated our EMG-driven modeling method using data collected from a
high-functioning hemiparetic subject walking on an instrumented treadmill at
speeds ranging from 0.4 to 0.8 m/s. EMG-driven model parameter values were
calibrated to match inverse dynamic moments for five degrees of freedom in each
leg while keeping musculoskeletal geometry close to that of an initial scaled
musculoskeletal model. We found that our EMG-driven modeling method incorporating
automated adjustment of musculoskeletal geometry predicted net joint moments
during walking more accurately than did the same method without geometric
adjustments. Geometric adjustments improved moment prediction errors by 25% on
average and up to 52%, with the largest improvements occurring at the hip.
Predicted adjustments to musculoskeletal geometry were comparable to errors
reported in the literature between scaled generic geometric models and
measurements made from imaging data. Our results demonstrate that with
appropriate experimental data, joint moment predictions for walking generated by
an EMG-driven model can be improved significantly when automated adjustment of
musculoskeletal geometry is included in the model calibration process.
PMID- 28700709
TI - Eye movement activity in normal human fetuses between 24 and 39 weeks of
gestation.
AB - Rapid eye movement (REM) sleep occurs throughout a relatively large proportion of
early development, and normal REM activity appears to be required for healthy
brain development. The eye movements (EMs) observed during REM sleep are the most
distinctive characteristics of this state. EMs are used as an index of
neurological function postnatally, but no specific indices of EM activity exist
for fetuses. We aimed to identify and characterize EM activity, particularly EM
bursts suggestive of REM periods, in fetuses with a gestational age between 24
and 39 weeks. This cross-sectional study included 84 normal singleton
pregnancies. Fetal EMs were monitored using real-time ultrasonography for 60 min
and recorded as videos. The videos were manually converted into a time series of
EM events, which were then analyzed by piecewise linear regression for various EM
characteristics, including EM density, EM burst density, density of EMs in EM
bursts, and continuous EM burst time. Two critical points for EM density, EM
burst density, and density of EMs in EM bursts were evident at gestation weeks 28
29 and 36-37. Overall EM activity in human fetuses increased until 28-29 weeks of
gestation, then again from 36-37 to 38-39 weeks of gestation. These findings may
be useful for creating indices of fetal neurological function for prognostic
purposes.
PMID- 28700710
TI - T follicular helper cells regulate the activation of B lymphocytes and antibody
production during Plasmodium vivax infection.
AB - Although the importance of humoral immunity to malaria has been established,
factors that control antibody production are poorly understood. Follicular helper
T cells (Tfh cells) are pivotal for generating high-affinity, long-lived antibody
responses. While it has been proposed that expansion of antigen-specific Tfh
cells, interleukin (IL) 21 production and robust germinal center formation are
associated with protection against malaria in mice, whether Tfh cells are found
during Plasmodium vivax (P. vivax) infection and if they play a role during
disease remains unknown. Our goal was to define the role of Tfh cells during P.
vivax malaria. We demonstrate that P. vivax infection triggers IL-21 production
and an increase in Tfh cells (PD-1+ICOS+CXCR5+CD45RO+CD4+CD3+). As expected, FACS
sorted Tfh cells, the primary source of IL-21, induced immunoglobulin production
by purified naive B cells. Furthermore, we found that P. vivax infection alters
the B cell compartment and these alterations were dependent on the number of
previous infections. First exposure leads to increased proportions of activated
and atypical memory B cells and decreased frequencies of classical memory B
cells, whereas patients that experienced multiple episodes displayed lower
proportions of atypical B cells and higher frequencies of classical memory B
cells. Despite the limited sample size, but consistent with the latter finding,
the data suggest that patients who had more than five infections harbored more
Tfh cells and produce more specific antibodies. P. vivax infection triggers IL-21
production by Tfh that impact B cell responses in humans.
PMID- 28700711
TI - Non-vitamin K oral anticoagulants are non-inferior for stroke prevention but
cause fewer major bleedings than well-managed warfarin: A retrospective register
study.
AB - BACKGROUND: For patients with atrial fibrillation, non-vitamin K oral
anticoagulants, or NOACs (dabigatran, rivaroxaban, edoxaban, and apixaban) have
been proven non-inferior or superior to warfarin in preventing stroke and
systemic embolism, and in risk of haemorrhage. In the pivotal NOAC studies,
quality of warfarin treatment was poor with mean time in therapeutic range (TTR)
55-65%, compared with >=70% in Swedish clinical practice. METHODS: We compared
NOACs (as a group) to warfarin in non-valvular atrial fibrillation, studying all
12,694 patients starting NOAC treatment within the Swedish clinical register and
dosing system Auricula, from July 1, 2011 to December 31, 2014, and matching them
to 36,317 patients starting warfarin using propensity scoring. Endpoints were
thromboembolic events and major bleedings that were fatal or required hospital
care. Outcome data were collected from validated Swedish hospital administrative
and clinical registers. RESULTS: Mean age was 72.2 vs 72.3 years, proportion of
males 58.2% vs 57.0%, and mean follow-up time 299 vs 283 days for NOACs and
warfarin. Distribution of NOACs was: dabigatran 40.3%, rivaroxaban 31.2%, and
apixaban 28.5%. Mean TTR was 70%. There were no significant differences in rates
of thromboembolic/thrombotic events or gastrointestinal bleeding. NOAC treated
patients had lower rates of major bleeding overall, hazard ratio 0.78 (95%
confidence interval 0.67-0.92), intracranial bleeding 0.59 (0.40-0.87),
haemorrhagic stroke 0.49 (0.28-0.86), and other major bleeding 0.71 (0.57-0.89).
CONCLUSION: For patients with atrial fibrillation, NOACs are as effective for
stroke prevention as well-managed warfarin but cause fewer major bleedings.
PMID- 28700712
TI - Correction: Does flooding effect the apparent survival and body condition of a
ground foraging migrant passerine?
AB - [This corrects the article DOI: 10.1371/journal.pone.0175179.].
PMID- 28700713
TI - Increased urinary prostaglandin E2 metabolite: A potential therapeutic target of
Gitelman syndrome.
AB - BACKGROUND: Gitelman syndrome (GS), an inherited autosomal recessive salt-losing
renal tubulopathy caused by mutations in SLC12A3 gene, has been associated with
normal prostaglandin E2 (PGE2) levels since 1995 by a study involving 11
clinically diagnosed patients. However, it is difficult to explain why
cyclooxygenase-2 (COX2) inhibitors, which pharmacologically reduce PGE2
synthesis, are helpful to patients with GS, and few studies performed in the last
20 years have measured PGE2 levels. The relationships between the clinical
manifestations and PGE2 levels were never thoroughly analyzed. METHODS: This
study involved 39 GS patients diagnosed by SLC12A3 gene sequencing. Plasma and 24
h urine samples as well as the clinical data were collected at admission. PGE2
and PGEM levels were detected in plasma and urine samples by enzyme immunoassays.
The in vivo function of the sodium-chloride co-transporter (NCC) in GS patients
was evaluated using a modified thiazide test. The association among PGE2 levels,
clinical manifestations and the function of NCC in GS patients were analyzed.
RESULTS: Significantly higher levels of urinary and plasma PGEM were observed in
GS patients than in the healthy volunteers. Higher urinary PGEM levels indicated
more severe clinical manifestations and NCC dysfunction estimated by the increase
of Cl- clearance. A higher PGEM level was found in male GS patients, who showed
earlier onset age and more severe hypokalemia, hypochloremia and metabolic
alkalosis than female GS patients. No relationship between renin angiotensin
aldosterone system activation and PGEM level was observed. CONCLUSIONS: Higher
urinary PGEM levels indicated more severe clinical manifestations and NCC
dysfunction in GS patients. COX2 inhibition might be a potential therapeutic
target in GS patients with elevated PGEM levels.
PMID- 28700714
TI - Genome wide re-sequencing of newly developed Rice Lines from common wild rice
(Oryza rufipogon Griff.) for the identification of NBS-LRR genes.
AB - Common wild rice (Oryza rufipogon Griff.) is an important germplasm for rice
breeding, which contains many resistance genes. Re-sequencing provides an
unprecedented opportunity to explore the abundant useful genes at whole genome
level. Here, we identified the nucleotide-binding site leucine-rich repeat (NBS
LRR) encoding genes by re-sequencing of two wild rice lines (i.e. Huaye 1 and
Huaye 2) that were developed from common wild rice. We obtained 128 to 147
million reads with approximately 32.5-fold coverage depth, and uniquely covered
more than 89.6% (> = 1 fold) of reference genomes. Two wild rice lines showed
high SNP (single-nucleotide polymorphisms) variation rate in 12 chromosomes
against the reference genomes of Nipponbare (japonica cultivar) and 93-11 (indica
cultivar). InDels (insertion/deletion polymorphisms) count-length distribution
exhibited normal distribution in the two lines, and most of the InDels were
ranged from -5 to 5 bp. With reference to the Nipponbare genome sequence, we
detected a total of 1,209,308 SNPs, 161,117 InDels and 4,192 SVs (structural
variations) in Huaye 1, and 1,387,959 SNPs, 180,226 InDels and 5,305 SVs in Huaye
2. A total of 44.9% and 46.9% genes exhibited sequence variations in two wild
rice lines compared to the Nipponbare and 93-11 reference genomes, respectively.
Analysis of NBS-LRR mutant candidate genes showed that they were mainly
distributed on chromosome 11, and NBS domain was more conserved than LRR domain
in both wild rice lines. NBS genes depicted higher levels of genetic diversity in
Huaye 1 than that found in Huaye 2. Furthermore, protein-protein interaction
analysis showed that NBS genes mostly interacted with the cytochrome C protein
(Os05g0420600, Os01g0885000 and BGIOSGA038922), while some NBS genes interacted
with heat shock protein, DNA-binding activity, Phosphoinositide 3-kinase and a
coiled coil region. We explored abundant NBS-LRR encoding genes in two common
wild rice lines through genome wide re-sequencing, which proved to be a useful
tool to exploit elite NBS-LRR genes in wild rice. The data here provide a
foundation for future work aimed at dissecting the genetic basis of disease
resistance in rice, and the two wild rice lines will be useful germplasm for the
molecular improvement of cultivated rice.
PMID- 28700715
TI - The pharmacological and non-pharmacological treatment of attention deficit
hyperactivity disorder in children and adolescents: A systematic review with
network meta-analyses of randomised trials.
AB - BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is one of the most
commonly diagnosed psychiatric disorders in childhood. A wide variety of
treatments have been used for the management of ADHD. We aimed to compare the
efficacy and safety of pharmacological, psychological and complementary and
alternative medicine interventions for the treatment of ADHD in children and
adolescents. METHODS AND FINDINGS: We performed a systematic review with network
meta-analyses. Randomised controlled trials (>= 3 weeks follow-up) were
identified from published and unpublished sources through searches in PubMed and
the Cochrane Library (up to April 7, 2016). Interventions of interest were
pharmacological (stimulants, non-stimulants, antidepressants, antipsychotics, and
other unlicensed drugs), psychological (behavioural, cognitive training and
neurofeedback) and complementary and alternative medicine (dietary therapy, fatty
acids, amino acids, minerals, herbal therapy, homeopathy, and physical activity).
The primary outcomes were efficacy (treatment response) and acceptability (all
cause discontinuation). Secondary outcomes included discontinuation due to
adverse events (tolerability), as well as serious adverse events and specific
adverse events. Random-effects Bayesian network meta-analyses were conducted to
obtain estimates as odds ratios (ORs) with 95% credibility intervals. We analysed
interventions by class and individually. 190 randomised trials (52 different
interventions grouped in 32 therapeutic classes) that enrolled 26114 participants
with ADHD were included in complex networks. At the class level, behavioural
therapy (alone or in combination with stimulants), stimulants, and non-stimulant
seemed significantly more efficacious than placebo. Behavioural therapy in
combination with stimulants seemed superior to stimulants or non-stimulants.
Stimulants seemed superior to behavioural therapy, cognitive training and non
stimulants. Behavioural therapy, stimulants and their combination showed the best
profile of acceptability. Stimulants and non-stimulants seemed well tolerated.
Among medications, methylphenidate, amphetamine, atomoxetine, guanfacine and
clonidine seemed significantly more efficacious than placebo. Methylphenidate and
amphetamine seemed more efficacious than atomoxetine and guanfacine.
Methylphenidate and clonidine seemed better accepted than placebo and
atomoxetine. Most of the efficacious pharmacological treatments were associated
with harms (anorexia, weight loss and insomnia), but an increased risk of serious
adverse events was not observed. There is lack of evidence for cognitive
training, neurofeedback, antidepressants, antipsychotics, dietary therapy, fatty
acids, and other complementary and alternative medicine. Overall findings were
limited by the clinical and methodological heterogeneity, small sample sizes of
trials, short-term follow-up, and the absence of high-quality evidence;
consequently, results should be interpreted with caution. CONCLUSIONS: Clinical
differences may exist between the pharmacological and non-pharmacological
treatment used for the management of ADHD. Uncertainties about therapies and the
balance between benefits, costs and potential harms should be considered before
starting treatment. There is an urgent need for high-quality randomised trials of
the multiple treatments for ADHD in children and adolescents. PROSPERO, number
CRD42014015008.
PMID- 28700716
TI - Improved high sensitivity screen for Huntington disease using a one-step triplet
primed PCR and melting curve assay.
AB - Molecular diagnosis of Huntington disease (HD) is currently performed by
fluorescent repeat-flanking or triplet-primed PCR (TP-PCR) with capillary
electrophoresis (CE). However, CE requires multiple post-PCR steps and may result
in high cost in high-throughput settings. We previously described a cost
effective single-step molecular screening strategy employing the use of melting
curve analysis (MCA). However, because it relies on repeat-flanking PCR, its
efficiency in detecting expansion mutations decreases with increasing size of the
repeat, which could lead to false-negative results. To address this pitfall, we
have developed an improved screening assay coupling TP-PCR, which has been shown
in CE-based assays to detect all expanded alleles regardless of size, with MCA in
a rapid one-step assay. A companion protocol for rapid size confirmation of
expansion-positive samples is also described. The assay was optimized on 30
genotype-known DNAs, and two plasmids pHTT(CAG)26 and pHTT(CAG)33 were used to
establish the threshold temperatures (TTs) distinguishing normal from expansion
positive samples. In contrast to repeat-flanking PCR MCA, TP-PCR MCA displayed
much higher sensitivity for detecting large expansions. All 30 DNAs generated
distinct melt peak Tms which correlated well with each sample's larger allele.
Normal samples were clearly distinguished from affected samples. The companion
sizing protocol accurately sized even the largest expanded allele of ~180 CAGs.
Blinded analysis of 69 clinical samples enriched for HD demonstrated 100% assay
sensitivity and specificity in sample segregation. The assay targets the HTT CAG
repeat specifically, tolerates a wide range of input DNA, and works well using
DNA from saliva and buccal swab in addition to blood. Therefore, rapid, accurate,
reliable, and high-throughput detection/exclusion of HD can be achieved using
this one-step screening assay, at less than half the cost of fluorescent PCR with
CE.
PMID- 28700717
TI - Integrated analysis of zone-specific protein and metabolite profiles within
nitrogen-fixing Medicago truncatula-Sinorhizobium medicae nodules.
AB - Symbiotic nitrogen fixation (SNF) between rhizobia and legumes requires metabolic
coordination within specialized root organs called nodules. Nodules formed in the
symbiosis between S. medicae and barrel medic (M. truncatula) are indeterminate,
cylindrical, and contain spatially distinct developmental zones. Bacteria in the
infection zone II (ZII), interzone II-III (IZ), and nitrogen fixation zone III
(ZIII) represent different stages in the metabolic progression from free-living
bacteria into nitrogen fixing bacteroids. To better understand the coordination
of plant and bacterial metabolism within the nodule, we used liquid and gas
chromatography coupled to tandem mass spectrometry (MS) to observe protein and
metabolite profiles representative of ZII, IZ, ZIII, whole-nodule, and primary
root. Our MS-based approach confidently identified 361 S. medicae proteins and
888 M. truncatula proteins, as well as 160 metabolites from each tissue. The data
are consistent with several organ- and zone-specific protein and metabolite
localization patterns characterized previously. We used our comprehensive dataset
to demonstrate how multiple branches of primary metabolism are coordinated
between symbionts and zones, including central carbon, fatty acid, and amino acid
metabolism. For example, M. truncatula glycolysis enzymes accumulate from zone I
to zone III within the nodule, while equivalent S. medicae enzymes decrease in
abundance. We also show the localization of S. medicae's transition to
dicarboxylic acid-dependent carbon metabolism within the IZ. The spatial
abundance patterns of S. medicae fatty acid (FA) biosynthesis enzymes indicate an
increased demand for FA production in the IZ and ZIII as compared to ZI. These
observations provide a resource for those seeking to understand coordinated
physiological changes during the development of SNF.
PMID- 28700718
TI - Reduction of diabetes-related distress predicts improved depressive symptoms: A
secondary analysis of the DIAMOS study.
AB - OBJECTIVE: Depressive symptoms in people with diabetes are associated with
increased risk of adverse outcomes. Although successful psychosocial treatment
options are available, little is known about factors that facilitate treatment
response for depression in diabetes. This prospective study aims to examine the
impact of known risk factors on improvement of depressive symptoms with a special
interest in the role of diabetes-related distress. METHODS: 181 people with
diabetes participated in a randomized controlled trial. Diabetes-related distress
was assessed using the Problem Areas In Diabetes (PAID) scale; depressive
symptoms were assessed using the Center for Epidemiologic Studies Depression (CES
D) scale. Multiple logistic and linear regression analyses were used to assess
associations between risk factors for depression (independent variables) and
improvement of depressive symptoms (dependent variable). Reliable change indices
were established as criteria of meaningful reductions in diabetes distress and
depressive symptoms. RESULTS: A reliable reduction of diabetes-related distress
(15.43 points in the PAID) was significantly associated with fourfold increased
odds for reliable improvement of depressive symptoms (OR = 4.25, 95% CI: 2.05
8.79; P<0.001). This result was corroborated using continuous measures of
diabetes distress and depressive symptoms, showing that greater reduction of
diabetes-related distress independently predicted greater improvement in
depressive symptoms (beta = -0.40; P<0.001). Higher age had a positive (Odds
Ratio = 2.04, 95% CI: 1.21-3.43; P<0.01) and type 2 diabetes had a negative
effect on the meaningful reduction of depressive symptoms (Odds Ratio = 0.12, 95%
CI: 0.04-0.35; P<0.001). CONCLUSIONS: The reduction of diabetes distress is a
statistical predictor of improvement of depressive symptoms. Diabetes patients
with comorbid depressive symptomatology might benefit from treatments to reduce
diabetes-related distress.
PMID- 28700719
TI - Stair negotiation made easier using novel interactive energy-recycling assistive
stairs.
AB - Here we show that novel, energy-recycling stairs reduce the amount of work
required for humans to both ascend and descend stairs. Our low-power,
interactive, and modular steps can be placed on existing staircases, storing
energy during stair descent and returning that energy to the user during stair
ascent. Energy is recycled through event-triggered latching and unlatching of
passive springs without the use of powered actuators. When ascending the energy
recycling stairs, naive users generated 17.4 +/- 6.9% less positive work with
their leading legs compared to conventional stairs, with the knee joint positive
work reduced by 37.7 +/- 10.5%. Users also generated 21.9 +/- 17.8% less negative
work with their trailing legs during stair descent, with ankle joint negative
work reduced by 26.0 +/- 15.9%. Our low-power energy-recycling stairs have the
potential to assist people with mobility impairments during stair negotiation on
existing staircases.
PMID- 28700720
TI - Altered cerebral blood flow velocity features in fibromyalgia patients in resting
state conditions.
AB - The aim of this study is to characterize in resting-state conditions the cerebral
blood flow velocity (CBFV) signals of fibromyalgia patients. The anterior and
middle cerebral arteries of both hemispheres from 15 women with fibromyalgia and
15 healthy women were monitored using Transcranial Doppler (TCD) during a 5
minute eyes-closed resting period. Several signal processing methods based on
time, information theory, frequency and time-frequency analyses were used in
order to extract different features to characterize the CBFV signals in the
different vessels. Main results indicated that, in comparison with control
subjects, fibromyalgia patients showed a higher complexity of the envelope CBFV
and a different distribution of the power spectral density. In addition, it has
been observed that complexity and spectral features show correlations with
clinical pain parameters and emotional factors. The characterization features
were used in a lineal model to discriminate between fibromyalgia patients and
healthy controls, providing a high accuracy. These findings indicate that CBFV
signals, specifically their complexity and spectral characteristics, contain
information that may be relevant for the assessment of fibromyalgia patients in
resting-state conditions.
PMID- 28700721
TI - Niche shifts and the potential distribution of Phenacoccus solenopsis (Hemiptera:
Pseudococcidae) under climate change.
AB - The cotton mealybug, Phenacoccus solenopsis Tinsley (Hemiptera: Pseudococcidae),
is a serious invasive species that significantly damages plants of approximately
60 families around the world. It is originally from North America and has also
been introduced to other continents. Our goals were to create a current and
future potential global distribution map for this pest under climate change with
MaxEnt software. We tested the hypothesis of niche conservatism for P. solenopsis
by comparing its native niche in North America to its invasive niches on other
continents using Principal components analyses (PCA) in R. The potentially
suitable habitat for P. solenopsis in its native and non-native ranges is
presented in the present paper. The results suggested that the mean temperature
of the wettest quarter and the mean temperature of the driest quarter are the
most important environmental variables determining the potential distribution of
P. solenopsis. We found strong evidence for niche shifts in the realized climatic
niche of this pest in South America and Australia due to niche unfilling;
however, a niche shift in the realized climatic niche of this pest in Eurasian
owing to niche expansion.
PMID- 28700722
TI - Anti-inflammatory properties of extracts from Chimonanthus nitens Oliv. leaf.
AB - Chimonanthus nitens Oliv. (CN) is a species in the family Calycanthaceae. Its
leaf is widely used to make traditional herbal tea in southern China and has a
wide range of therapeutic effects. The profile of the ethanol extracts from CN
leaves was identified by UPLC-QTOF-MS/MS. Forty seven compounds were determined
including organic acids, phenolic acids and derivatives, flavonoids, coumarins,
fatty acids and other compounds. The effect of the CN extracts on the
inflammatory damage in zebrafish and in RAW 264.7 cells was investigated. The
extracts demonstrated a strong ability to inhibit the recruitment of neutrophils
in LPS-stimulated zebrafish, but macrophage migration was not significantly
affected. Pro-inflammatory cytokines (i.e., TNF-alpha, IL-6 and IL-1beta) were
also determined by q-PCR. The extracts strongly reduced mRNA expression of TNF
alpha, IL-6 but not IL-1beta in zebrafish model, while significantly inhibited
the production of the factors in the RAW 264.7 cells. Therefore, our results
suggest that the ethanol extracts of CN leaves may serve as a source of
nutraceutical compounds with anti-inflammatory properties.
PMID- 28700723
TI - Position effects influencing intrachromosomal repair of a double-strand break in
budding yeast.
AB - Repair of a double-strand break (DSB) by an ectopic homologous donor sequence is
subject to the three-dimensional arrangement of chromosomes in the nucleus of
haploid budding yeast. The data for interchromosomal recombination suggest that
searching for homology is accomplished by a random collision process, strongly
influenced by the contact probability of the donor and recipient sequences. Here
we explore how recombination occurs on the same chromosome and whether there are
additional constraints imposed on repair. Specifically, we examined how
intrachromosomal repair is affected by the location of the donor sequence along
the 813-kb chromosome 2 (Chr2), with a site-specific DSB created on the right arm
(position 625 kb). Repair correlates well with contact frequencies determined by
chromosome conformation capture-based studies (r = 0.85). Moreover, there is a
profound constraint imposed by the anchoring of the centromere (CEN2, position
238 kb) to the spindle pole body. Sequences at the same distance on either side
of CEN2 are equivalently constrained in recombining with a DSB located more
distally on one arm, suggesting that sequences on the opposite arm from the DSB
are not otherwise constrained in their interaction with the DSB. The centromere
constraint can be partially relieved by inducing transcription through the
centromere to inactivate CEN2 tethering. In diploid cells, repair of a DSB via
its allelic donor is strongly influenced by the presence and the position of an
ectopic intrachromosomal donor.
PMID- 28700724
TI - OPTiM: Optical projection tomography integrated microscope using open-source
hardware and software.
AB - We describe the implementation of an OPT plate to perform optical projection
tomography (OPT) on a commercial wide-field inverted microscope, using our open
source hardware and software. The OPT plate includes a tilt adjustment for
alignment and a stepper motor for sample rotation as required by standard
projection tomography. Depending on magnification requirements, three methods of
performing OPT are detailed using this adaptor plate: a conventional direct OPT
method requiring only the addition of a limiting aperture behind the objective
lens; an external optical-relay method allowing conventional OPT to be performed
at magnifications >4x; a remote focal scanning and region-of-interest method for
improved spatial resolution OPT (up to ~1.6 MUm). All three methods use the
microscope's existing incoherent light source (i.e. arc-lamp) and all of its
inherent functionality is maintained for day-to-day use. OPT acquisitions are
performed on in vivo zebrafish embryos to demonstrate the implementations'
viability.
PMID- 28700725
TI - Correction: A selection study on a laboratory-designed population of salmon lice
(Lepeophtheirus salmonis) using organophosphate and pyrethroid pesticides.
AB - [This corrects the article DOI: 10.1371/journal.pone.0178068.].
PMID- 28700726
TI - Integer programming for improving radiotherapy treatment efficiency.
AB - BACKGROUND AND PURPOSE: Patients received by radiotherapy departments are diverse
and may be diagnosed with different cancers. Therefore, they need different
radiotherapy treatment plans and thus have different needs for medical resources.
This research aims to explore the best method of scheduling the admission of
patients receiving radiotherapy so as to reduce patient loss and maximize the
usage efficiency of service resources. MATERIALS AND METHODS: A mix integer
programming (MIP) model integrated with special features of radiotherapy is
constructed. The data used here is based on the historical data collected and we
propose an exact method to solve the MIP model. RESULTS: Compared with the
traditional First Come First Served (FCFS) method, the new method has boosted
patient admission as well as the usage of linear accelerators (LINAC) and beds.
CONCLUSIONS: The integer programming model can be used to describe the complex
problem of scheduling radio-receiving patients, to identify the bottleneck
resources that hinder patient admission, and to obtain the optimal LINAC-bed
radio under the current data conditions. Different management strategies can be
implemented by adjusting the settings of the MIP model. The computational results
can serve as a reference for the policy-makers in decision making.
PMID- 28700727
TI - Longitudinal increases of brain metabolite levels in 5-10 year old children.
AB - Longitudinal magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI)
studies reveal significant changes in brain structure and structural networks
that occur together with cognitive and behavioral maturation in childhood.
However, the underlying cellular changes accompanying brain maturation are less
understood. Examining regional age-related changes in metabolite levels provides
insight into the physiology of neurodevelopment. Magnetic resonance spectroscopy
(MRS) measures localize brain metabolism. The majority of neuroimaging studies of
healthy development are from the developed world. In a longitudinal MRS study of
64 South African children aged 5 to 10 years old (29 female; 29 HIV exposed,
uninfected), we examined the age-related trajectories of creatine (Cr+PCr), N
acetyl-aspartate (NAA), the combined NAA+N-acetyl-aspartyl-glutamate (NAAG),
choline (GPC+PCh), glutamate (Glu) and the combined Glu+glutamine (Glu+Gln) in
voxels within gray and white matter, as well as subcortically in the basal
ganglia (BG). In frontal gray matter, we found age-related increases in Cr+PCr,
NAA, NAA+NAAG and Glu+Gln levels pointing to synaptic activity likely related to
learning. In the BG we observed increased levels of Glu, Glu+Gln and NAA+NAAG
with age that point to subcortical synaptic reorganization. In white matter, we
found increased levels of Cr+PCr, NAA, NAA+NAAG, Glu and Glu+Gln with age,
implicating these metabolites in ongoing myelination. We observed no sex-age or
HIV exposure-age interactions, indicating that physiological changes are
independent of sex during this time period. The metabolite trajectories
presented, therefore, provide a critical benchmark of normal cellular growth for
a low socioeconomic pediatric population in the developing world against which
pathology and abnormal development may be compared.
PMID- 28700728
TI - Demographics as predictors of suicidal thoughts and behaviors: A meta-analysis.
AB - BACKGROUND: Certain demographic factors have long been cited to confer risk or
protection for suicidal thoughts and behaviors. However, many studies have found
weak or non-significant effects. Determining the effect strength and clinical
utility of demographics as predictors is crucial for suicide risk assessment and
theory development. As such, we conducted a meta-analysis to determine the effect
strength and clinical utility of demographics as predictors. METHODS: We searched
PsycInfo, PubMed, and GoogleScholar for studies published before January 1st,
2015. Inclusion criteria required that studies use at least one demographic
factor to longitudinally predict suicide ideation, attempt, or death. The initial
search yielded 2,541 studies, 159 of which were eligible. A total of 752 unique
statistical tests were included in analysis. RESULTS: Suicide death was the most
commonly studied outcome, followed by attempt and ideation. The average follow-up
length was 9.4 years. The overall effects of demographic factors studied in the
field as risk factors were significant but weak, and that of demographic factors
studied as protective factors were non-significant. Adjusting for publication
bias further reduced effect estimates. No specific demographic factors appeared
to be strong predictors. The effects were consistent across multiple moderators.
CONCLUSIONS: At least within the narrow methodological constraints of the
existing literature, demographic factors were statistically significant risk
factors, but not protective factors. Even as risk factors, demographics offer
very little improvement in predictive accuracy. Future studies that go beyond the
limitations of the existing literature are needed to further understand the
effects of demographics.
PMID- 28700729
TI - The association between electronic-cigarette use and self-reported oral symptoms
including cracked or broken teeth and tongue and/or inside-cheek pain among
adolescents: A cross-sectional study.
AB - BACKGROUND: Little is known about oral health related to electronic-cigarette
(EC) use, even though EC use is increasing rapidly. The aim of this study is to
assess the relationship between EC use and oral health, including 'gingival pain
and/or bleeding', 'tongue and/or inside-cheek pain', and 'cracked or broken
teeth' among adolescents. METHODS: A total of 65,528 students in 2016 were
included in this cross-sectional study. RESULTS: For EC use, 0.5% (n = 297)
students were daily users, 1.9% (n = 1259) were '1 to 29 days past month users',
and 5.9% (n = 3848) were former users. Overall, 18.5% students reported they had
experienced 'gingival pain and/or bleeding', 11.0% reported 'tongue and/or inside
cheek pain', and 11.4% reported a 'cracked or broken tooth' within the past 12
months. When comparing 'daily EC users', '1 to 29 days past month EC users', and
'former EC users' with 'never EC users', the adjusted ORs for 'cracked or broken
tooth' were 1.65 (95% CI: 1.19-2.27), 1.26 (95% CI: 1.06-1.51), and 1.16 (95% CI:
1.04-1.30), respectively. Comparing 'daily EC users' with 'never EC users', the
adjusted OR for 'tongue and/or inside-cheek pain' was 1.54 (1.05-2.26). However,
EC use among adolescents was not associated with 'gingival pain and/or bleeding'
when adjusted for the potential confounders. CONCLUSIONS: Based on the results,
the odds of cracked or broken teeth among daily, '1 to 29 days past month', and
former EC users were significantly higher than those among never EC users. The
odds of tongue and/or inside-cheek pain among daily EC users were significantly
higher than those among never EC users. In conclusion, the results suggest that
daily EC use among adolescents may be a risk factor for cracked or broken teeth
and tongue and/or inside-cheek pain.
PMID- 28700730
TI - Pediatric autoimmune hepatitis shows a disproportionate decline of regulatory T
cells in the liver and of IL-2 in the blood of patients undergoing therapy.
AB - BACKGROUND & AIMS: The autoimmune hepatitis (AIH) is a chronic hepatitis driven
by the adaptive immunity that affects all age groups. A functional and numerical
regulatory T cell (Treg) defect has been reported in pediatric AIH (pAIH), while
an intrahepatic increase in adult AIH (aAIH) patients has been detected in
current research findings. METHODS: Therefore, we quantified the intrahepatic
numbers of Treg, T and B cells, as well as serum cytokine levels before and
during therapy in pAIH. RESULTS: We found a disproportional intrahepatic
enrichment of Tregs in untreated pAIH compared to pediatric non-alcoholic fatty
liver disease. The increase of Treg/total T cells was even more pronounced than
in aAIH due to fewer infiltrating T and B cells. Portal densities of Treg, as
well as total T and B cells, declined significantly during therapy. However,
portal Treg densities decreased disproportionately, leading to even decreasing
ratios of Treg to T and B cells during therapy. Out of 28 serum cytokines IL-2
showed the strongest (10fold) decrease under therapy. This decline of IL-2 was
associated with decreasing intrahepatic Treg numbers under therapy. None of the
baseline T and B cell infiltration parameters were associated with the subsequent
treatment response in pAIH. CONCLUSIONS: Intrahepatic Tregs are rather enriched
in untreated pAIH. The disproportional decrease of Tregs during therapy may be
caused by a decrease of IL-2 levels. New therapies should, therefore, aim in
strengthening intrahepatic immune regulation.
PMID- 28700731
TI - Forward flexion of trunk in Parkinson's disease patients is affected by
subjective vertical position.
AB - PURPOSE: No method has been established to evaluate the dissociation between
subjective and objective vertical positions with respect to the self-awareness of
postural deformity in patients with Parkinson's disease (PD). The purpose of this
study was to demonstrate, from the relationship between an assessment of the
dissociation of subjective and objective vertical positions of PD patients and an
assessment based on established PD clinical evaluation scales, that the
dissociation regarding vertical position is a factor in the severity of the
forward flexion of trunk (FFT). METHODS: Subjects were 39 PD patients and 15 age
matched healthy individuals (control group). Posture was evaluated with
measurement of FFT angle during static standing and the subjective vertical
position (SV) of the patient. For evaluation of motor function, the Modified
Hoehn & Yahr scale, Unified Parkinson's Disease Rating Scale (UPDRS), 3-m Timed
Up and Go Test (TUG), and Functional Reach Test (FRT) were used. RESULTS: In PD
patients, FFT angle in the 3rd tertile of patients was 13.8+/-9.7 degrees ,
significantly greater than those in the control group and the 1st and 2nd
tertiles of PD patients (control group vs 3rd tertile, p = 0.008; 1st tertile vs
3rd tertile, p<0.001; 2nd vs 3rd tertile, p = 0.008). In multiple regression
analysis for factors in the FFT angle, significant factors were SV, disease
duration, and the standard deviation of each SV angle measurement. CONCLUSION:
The dissociation between SV and objective vertical position affects the FFT of PD
patients, suggesting an involvement of non-basal ganglia pathologies.
PMID- 28700732
TI - Tissue plasminogen activator mediates deleterious complement cascade activation
in stroke.
AB - The use of intravenous tissue plasminogen activator (tPA) in the treatment of
ischemic stroke is limited by its propensity to exacerbate brain edema and
hemorrhage. The mechanisms underlying these deleterious effects of tPA remain
incompletely understood. The purpose of this study was to delineate a pathway of
tPA-mediated complement cascade activation in stroke and to determine whether
complement inhibition ameliorates the adverse effects of post-ischemic tPA
administration. We found that tPA promotes C3 cleavage both in vitro and in
ischemic brain through a plasmin-mediated extrinsic pathway. Using cell culture
models, we then showed that the C3a-receptor is strongly expressed on ischemic
endothelium and that exogenous C3a dramatically enhances endothelial cell
permeability. Next, we assessed the effect of tPA administration on brain edema
and hemorrhage in a transient model of focal cerebral ischemia in C57BL/6 mice.
We found that intravenous tPA exacerbates brain edema and hemorrhage in stroke,
and that these effects are abrogated by a small-molecule antagonist of the C3a
receptor. These findings establish for the first time that intravenous tPA
dramatically upregulates complement cascade activation in ischemic brain and that
pharmacologic complement inhibition protects against the adverse effects of tPA
mediated thrombolysis in stroke.
PMID- 28700733
TI - Non-invasive prediction of preterm birth in women with cervical insufficiency or
an asymptomatic short cervix (<=25 mm) by measurement of biomarkers in the
cervicovaginal fluid.
AB - OBJECTIVE: To determine whether various proteins in the cervicovaginal fluid
(CVF) known to be involved in immune regulation, alone or in combination with
clinical risk factors, can predict spontaneous preterm delivery (SPTD) in women
with cervical insufficiency or a short cervix (<=25 mm). METHODS: This
retrospective cohort study included 62 asymptomatic women with cervical
insufficiency (n = 27) or an asymptomatic short cervix (n = 35) at 18-27 weeks.
CVF swab samples were taken for assays of vitamin D binding protein (VDBP),
interleukin (IL)-8, matrix metalloproteinases (MMP)-9, tissue inhibitor of
metalloproteinases (TIMP)-1, and Dickkopf-related protein 3 (DKK3) before
cervical examination, and maternal blood was collected for the determination of
the C-reactive protein (CRP) level. The primary outcome measurement was SPTD at
<32 weeks of gestation. Logistic regression analysis and receiver operating
characteristic curves were used for the statistical analyses. RESULTS: The rate
of SPTD at <32 weeks was 40.3% (25/62). The CVF levels of VDBP, TIMP-1, and DKK3,
but not IL-8 and MMP-9, were significantly higher in the women who had SPTD at
<32 weeks than in those who did not deliver spontaneously at <32 weeks. The women
who had SPTD at <32 weeks had a significantly more advanced cervical dilatation
at presentation and a higher level of serum CRP. Using the stepwise regression
analysis, a prediction model was developed by combining various proteins in the
CVF and clinical factors, resulting in the inclusion of cervical dilatation, CVF
VDBP, and use of corticosteroids (area under curve, 0.909). CONCLUSIONS: In women
with cervical insufficiency or a short cervix, VDBP, TIMP-1, and DKK3 in the CVF
may be useful as non-invasive predictors of SPTD at <32 weeks. A combination of
these markers and clinical factors appears to improve the predictability of SPTD
compared with the markers alone.
PMID- 28700734
TI - Molecular evolution of versatile derivatives from a GFP-like protein in the
marine copepod Chiridius poppei.
AB - Fluorescent proteins are now indispensable tools in molecular research. They have
also been adapted for a wide variety of uses in cases involving creative
applications, including textiles, aquarium fish, and ornamental plants. Our
colleagues have previously cloned a yellow GFP-like protein derived from the
marine copepod Chiridius poppei (YGFP), and moreover, succeeded in generating
transgenic flowers with clearly visible fluorescence, without the need for high
sensitivity imaging equipment. However, due to the low Stokes shift of YGFP (10
nm), it is difficult to separate emitted light of a labeled object from the light
used for excitation; hence, limitations for various applications remain. In this
study, which was aimed at developing YGFP mutants with increased Stokes shifts,
we conducted stepwise molecular evolution experiments on YGFP by screening random
mutations at three key amino acids, based on their fluorescent characteristics
and structural stabilities, followed by optimization of their fluorescence output
by DNA shuffling of the entire coding sequence. We successfully identified an
eYGFPuv that had an excitation maximum in UV wavelengths and a 24-fold increase
in fluorescence intensity compared to the previously reported YGFP mutant (H52D).
In addition, eYGFPuv exhibited almost 9-fold higher fluorescence intensity
compared to the commercially available GFPuv when expressed in human colon
carcinoma HCT116 cells and without any differences in cytotoxicity. Thus, this
novel mutant with the desirable characteristics of bright fluorescence, long
Stokes shift, and low cytotoxity, may be particularly well suited to a variety of
molecular and biological applications.
PMID- 28700735
TI - Molecular mechanisms by which casein glycomacropeptide maintains internal
homeostasis in mice with experimental ulcerative colitis.
AB - OBJECTIVES: The aim of this study was to elucidate the molecular mechanisms by
which food-derived casein glycomacropeptide (CGMP) maintains internal homeostasis
in the intestinal mucosa and to investigate the effects of CGMP on the intestinal
mucosal immunological barrier and related signal transduction pathways. METHODS:
In this study, a famoxadone (OXZ)-induced mouse experimental ulcerative colitis
(UC) model was built. The experimental UC mice were intragastrically administered
milk-derived CGMP for four consecutive days. The molecular mechanisms by which
milk-derived CGMP improved and restored the inflammatory status in UC symptoms
were elucidated by H&E staining, immunohistochemical staining and western
blotting. RESULTS: The results indicated that CGMP (50 mg/(kg bw.d)) could
significantly improve morphological injury to intestinal mucosa in OXZ-induced UC
mice to the same extent that did sulfasalazine (SASP, 40 mg/(kg bw.d)), a
medicine used to treat UC, in the control group. The study found that CGMP could
significantly reduce the expression of Human mucosal addressin cell adhesion
molecule-1 (MAdCAM-1), Cluster of differentiation 4 (CD4) and Cluster of
differentiation 8 (CD8) in the lamina propria of the intestinal mucosa and
significantly stimulate the secretion of sIgA to increase intestinal immunity.
Furthermore, CGMP was found to be directly involved in inhibiting the MAPK
pathway and activating the TGF-beta1/Smad signal transduction cascade, which
could maintain immunological regulation of the intestinal mucosa and protect the
functions of the intestinal mucosal barrier. CONCLUSIONS: This study elucidated
the molecular mechanisms by which CGMP maintained homeostasis of the intestinal
mucosa and further confirmed its pharmaceutical value as a food-derived
functional component with promising potential for further
exploration/utilization.
PMID- 28700736
TI - Short-term rehospitalization across the spectrum of age and insurance types in
the United States.
AB - Few studies have examined rates and causes of short-term readmissions among
adults across age and insurance types. We compared rates, characteristics, and
costs of 30-day readmission after all-cause hospitalizations across insurance
types in the US. We retrospectively evaluated alive patients >=18 years old,
discharged for any cause, 1/1/13-11/31/13, 2006 non-federal hospitals in 21
states in the Nationwide Readmissions Database. The primary stratification
variable of interest was primary insurance. Comorbid conditions were assessed
based on Elixhauser comorbidities, as defined by administrative billing codes.
Additional measures included diagnoses for index hospitalizations leading to
rehospitalization. Hierarchical multivariable logistic regression models, with
hospital site as a random effect, were used to calculate the adjusted odds of 30
day readmissions by age group and insurance categories. Cost and discharge
estimates were weighted per NRD procedures to reflect a nationally representative
sample. Diagnoses for index hospitalizations leading to rehospitalization were
determined. Among 12,533,551 discharges, 1,818,093 (14.5%) resulted in
readmission within 30 days. Medicaid insurance was associated with the highest
adjusted odds ratio (AOR) for readmission both in those >=65 years old (AOR 1.12,
95%CI 1.10-1.14; p <0.001), and 45-64 (AOR 1.67, 95% CI 1.66-1.69; p < 0.001),
and Medicare in the 18-44 group (Medicare vs. private insurance: AOR 1.99, 95% CI
1.96-2.01; p <0.001). Discharges for psychiatric or substance abuse disorders,
septicemia, and heart failure accounted for the largest numbers of readmissions,
with readmission rates of 24.0%, 17.9%, 22.9% respectively. Total costs for
readmissions were 50.7 billion USD, highest for Medicare (29.6 billion USD), with
non-Medicare costs exceeding 21 billion USD. While Medicare readmissions account
for more than half of the total burden of readmissions, costs of non-Medicare
readmissions are nonetheless substantial. Medicaid patients have the highest odds
of readmission in individuals older than age 44, commonly due to hospitalizations
for psychiatric illness and substance abuse disorders. Medicaid patients
represent a population at uniquely high risk for readmission.
PMID- 28700737
TI - Correction: Dendritic cell maturation, but not type I interferon exposure,
restricts infection by HTLV-1, and viral transmission to T-cells.
AB - [This corrects the article DOI: 10.1371/journal.ppat.1006353.].
PMID- 28700738
TI - Age dependent differences in the kinetics of gammadelta T cells after influenza
vaccination.
AB - Immunosenescence is a hallmark of the aging immune system and is considered the
main cause of a reduced vaccine efficacy in the elderly. Although gammadelta T
cells can become activated by recombinant influenza hemagglutinin, their age
related immunocompetence during a virus-induced immune response has so far not
been investigated. In this study we evaluate the kinetics of gammadelta T cells
after vaccination with the trivalent 2011/2012 northern hemisphere seasonal
influenza vaccine. We applied multi-parametric flow cytometry to a cohort of 21
young (19-30 years) and 23 elderly (53-67 years) healthy individuals. Activated
and proliferating gammadelta T cells, as identified by CD38 and Ki67 expression,
were quantified on the days 0, 3, 7, 10, 14, 17, and 21. We observed a
significantly lower number of activated and proliferating gammadelta T cells at
baseline and following vaccination in elderly as compared to young individuals.
The kinetics changes of activated gammadelta T cells were much stronger in the
young, while corresponding changes in the elderly occurred slower. In addition,
we observed an association between day 21 HAI titers of influenza A and the
frequencies of Ki67+ gammadelta T cells at day 7 in the young. In conclusion,
aging induces alterations of the gammadelta T cell response that might have
negative implications for vaccination efficacy.
PMID- 28700739
TI - Cysteine protects rabbit spermatozoa against reactive oxygen species-induced
damages.
AB - The process of cryopreservation results in over-production of reactive oxygen
species, which is extremely detrimental to spermatozoa. The aim of this study was
to investigate whether addition of cysteine to freezing extender would facilitate
the cryosurvival of rabbit spermatozoa, and if so, how cysteine protects
spermatozoa from cryodamages. Freshly ejaculated semen was diluted with Tris
citrate-glucose extender supplemented with different concentrations of cysteine.
The motility, intact acrosomes, membrane integrity, mitochondrial potentials, 8
hydroxyguanosine level and sperm-zona pellucida binding capacity were examined.
Furthermore, glutathione peroxidase (GPx) activity, glutathione content (GSH),
and level of reactive oxygen species (ROS) and hydrogen peroxide of spermatozoa
were analyzed. The values of motility, intact acrosomes, membrane integrity,
mitochondrial potentials and sperm-zona pellucida binding capacity of the frozen
thawed spermatozoa in the treatment of cysteine were significantly higher than
those of the control. Addition of cysteine to extenders improved the GPx activity
and GSH content of spermatozoa, while lowered the ROS, DNA oxidative alterations
and lipid peroxidation level, which makes spermatozoa avoid ROS to attack DNA,
the plasma membrane and mitochondria. In conclusion, cysteine protects
spermatozoa against ROS-induced damages during cryopreservation and post-thaw
incubation. Addition of cysteine is recommended to facilitate the improvement of
semen preservation for the rabbit breeding industry.
PMID- 28700740
TI - Navigation accuracy after automatic- and hybrid-surface registration in sinus and
skull base surgery.
AB - OBJECTIVE: Computer-aided-surgery in ENT surgery is mainly used for sinus surgery
but navigation accuracy still reaches its limits for skull base procedures.
Knowledge of navigation accuracy in distinct anatomical regions is therefore
mandatory. This study examined whether navigation accuracy can be improved in
specific anatomical localizations by using hybrid registration technique. STUDY
DESIGN: Experimental phantom study. SETTING: Operating room. SUBJECTS AND
METHODS: The gold standard of screw registration was compared with automatic LED
mask-registration alone, and in combination with additional surface matching. 3D
printer-based skull models with individual fabricated silicone skin were used for
the experiments. Overall navigation accuracy considering 26 target fiducials
distributed over each skull was measured as well as the accuracy on selected
anatomic localizations. RESULTS: Overall navigation accuracy was <1.0 mm in all
cases, showing the significantly lowest values after screw registration (0.66 +/-
0.08 mm), followed by hybrid registration (0.83+/- 0.08 mm), and sole mask
registration (0.92 +/- 0.13 mm).On selected anatomic localizations screw
registration was significantly superior on the sphenoid sinus and on the internal
auditory canal. However, mask registration showed significantly better accuracy
results on the midface. Navigation accuracy on skull base localizations could be
significantly improved by the combination of mask registration and additional
surface matching. CONCLUSION: Overall navigation accuracy gives no sufficient
information regarding navigation accuracy in a distinct anatomic area. The non
invasive LED-mask-registration proved to be an alternative in clinical routine
showing best accuracy results on the midface. For challenging skull base
procedures a hybrid registration technique is recommendable which improves
navigation accuracy significantly in this operating field. Invasive registration
procedures are reserved for selected challenging skull base operations where the
required high precision warrants the invasiveness.
PMID- 28700741
TI - Mononuclear-macrophages but not neutrophils act as major infiltrating anti
leptospiral phagocytes during leptospirosis.
AB - OBJECTIVE: To identify the major infiltrating phagocytes during leptospirosis and
examine the killing mechanism used by the host to eliminate Leptospira
interrogans. METHODS: Major infiltrating phagocytes in Leptospira-infected
C3H/HeJ mice were detected by immunohistochemistry. Chemokines and vascular
endothelial cell adhesion molecules (VECAMs) of Leptospira-infected mice and
leptospirosis patients were detected by microarray and immunohistochemistry.
Leptospira-phagocytosing and -killing abilities of human or mouse macrophages and
neutrophils, and the roles of intracellular ROS, NO and [Ca2+]i in Leptospira
killing process were evaluated by confocal microscopy and spectrofluorimetry.
RESULTS: Peripheral blood mononuclear-macrophages rather than neutrophils were
the main infiltrating phagocytes in the lungs, liver and kidneys of infected
mice. Levels of macrophage- but not neutrophil-specific chemokines and VECAMs
were significantly increased in the samples from infected mice and patients. All
macrophages tested had a higher ability than neutrophils to phagocytose and kill
leptospires. Higher ROS and NO levels and [Ca2+]i in the macrophages were
involved in killing leptospires. Human macrophages displayed more phagolysosome
formation and a stronger leptospire-killing ability to than mouse macrophages.
CONCLUSIONS: Mononuclear-macrophages but not neutrophils represent the main
infiltrating and anti-leptospiral phagocytes during leptospirosis. A lower level
of phagosome-lysosome fusion may be responsible for the lower Leptospira-killing
ability of human macrophages.
PMID- 28700742
TI - Direct medical cost associated with diabetic retinopathy severity in type 2
diabetes in Singapore.
AB - Diabetic retinopathy (DR) is a leading cause of vision-loss globally among type 2
diabetes (T2DM) patients. Information on the economic burden of DR in Singapore
is limited. We aim to identify the total annual direct medical costs of DR at
different stages, and to examine factors influencing the costs. Four hundreds and
seventy T2DM patients who attended the Diabetes Centre in a secondary hospital in
Singapore in 2011-2014 were included. Digital color fundus photographs were
assessed for DR in a masked fashion. Retinopathy severity was further categorized
into non-proliferative DR (NPDR), including mild, moderate and severe NPDR, and
proliferative DR (PDR). Medical costs were assessed using hospital administrative
data. DR was diagnosed in 172 (39.5%) patients, including 51 mild, 62 moderate
and 18 severe NPDR, and 41 PDR. The median cost in DR [2012.0 (1111.2-4192.3)]
was significantly higher than that in non-DR patients [1158.1 (724.1-1838.9)]
(p<0.001). The corresponding costs for mild, moderate, severe NPDR and PDR were
[1167.1 (895.4-2012.0)], [2212.0 (1215.5-3825.5)], [2717.5 (1444.0-6310.7)], and
[3594.8.1 (1978.4-8427.7)], respectively. After adjustment, the corresponding
cost ratios for mild, moderate, severe NPDR, and PDR relative to non-DR were 1.1
(p = 0.827), 1.8 (p = 0.003), 2.0 (p = 0.031) and 2.3 (p<0.001), respectively.
The other factors affecting the total cost include smoking (ratio = 1.7, p =
0.019), neuropathy (ratio = 1.9, p = 0.001) and chronic kidney disease (CKD)
(ratio = 1.4, p = 0.019). The presence and severity of DR was associated with
increased direct medical costs in T2DM. Our results suggest that preventing
progression of DR may reduce the economic burden of DR.
PMID- 28700743
TI - Polymorphisms in the vitamin D receptor gene are associated with reduced rate of
sputum culture conversion in multidrug-resistant tuberculosis patients in South
Africa.
AB - BACKGROUND: Vitamin D modulates the inflammatory and immune response to
tuberculosis (TB) and also mediates the induction of the antimicrobial peptide
cathelicidin. Deficiency of 25-hydroxyvitamin D and single nucleotide
polymorphisms (SNPs) in the vitamin D receptor (VDR) gene may increase the risk
of TB disease and decrease culture conversion rates in drug susceptible TB.
Whether these VDR SNPs are found in African populations or impact multidrug
resistant (MDR) TB treatment has not been established. We aimed to determine if
SNPs in the VDR gene were associated with sputum culture conversion among a
cohort of MDR TB patients in South Africa. METHODS: We conducted a prospective
cohort study of adult MDR TB patients receiving second-line TB treatment in
KwaZulu-Natal province. Subjects had monthly sputum cultures performed. In a
subset of participants, whole blood samples were obtained for genomic analyses.
Genomic DNA was extracted and genotyped with Affymetrix Axiom Pan-African Array.
Cox proportional models were used to determine the association between VDR SNPs
and rate of culture conversion. RESULTS: Genomic analyses were performed on 91
MDR TB subjects enrolled in the sub-study; 60% were female and median age was 35
years (interquartile range [IQR] 29-42). Smoking was reported by 21% of subjects
and most subjects had HIV (80%), were smear negative (57%), and had cavitary
disease (55%). Overall, 87 (96%) subjects initially converted cultures to
negative, with median time to culture conversion of 57 days (IQR 17-114). Of 121
VDR SNPs examined, 10 were significantly associated (p<0.01) with rate of sputum
conversion in multivariable analyses. Each additional risk allele on SNP
rs74085240 delayed culture conversion significantly (adjusted hazard ratio 0.30,
95% confidence interval 0.14-0.67). CONCLUSIONS: Polymorphisms in the VDR gene
were associated with rate of sputum culture conversion in MDR TB patients in this
high HIV prevalence setting in South Africa.
PMID- 28700744
TI - Hypermethylated DNA, a circulating biomarker for colorectal cancer detection.
AB - BACKGROUND: Colorectal cancer (CRC) is one of the most common cancers in the
western world. Screening is an efficient method of reducing cancer-related
mortality. Molecular biomarkers for cancer in general and CRC in particular have
been proposed, and hypermethylated DNA from stool or blood samples are already
implemented as biomarkers for CRC screening. We aimed to evaluate the performance
of proven hypermethylated DNA promoter regions as plasma based biomarkers for CRC
detection. METHODS: We conducted a cross-sectional case-control study of 193 CRC
patients and 102 colonoscopy-verified healthy controls. Using methylation
specific polymerase chain reaction, we evaluated 30 DNA promoter regions
previously found to be CRC specific. We used multivariable logistic regression
with stepwise backwards selection, and subsequent leave-pair-out cross
validation, to calculate the optimism corrected area under the receiver operating
characteristics curve (AUC) for all stage as well as early stage CRC. RESULTS:
None of the individual DNA promoter regions provided an overall sensitivity above
30% at a reasonable specificity. However, seven hypermethylated promoter regions
(ALX4, BMP3, NPTX2, RARB, SDC2, SEPT9, and VIM) along with the covariates sex and
age yielded an optimism corrected AUC of 0.86 for all stage CRC and 0.85 for
early stage CRC. Overall sensitivity for CRC detection was 90.7% at 72.5%
specificity using a cut point value of 0.5. CONCLUSIONS: Individual
hypermethylated DNA promoter regions have limited value as CRC screening markers.
However, a panel of seven hypermethylated promoter regions show great promise as
a model for CRC detection.
PMID- 28700745
TI - Spatial location of neutralizing and non-neutralizing B cell epitopes on domain 1
of ricin toxin's binding subunit.
AB - Ricin toxin's binding subunit (RTB) is a galactose-/N-acetylgalactosamine
(Gal/GalNac)-specific lectin that mediates uptake and intracellular trafficking
of ricin within mammalian cells. Structurally, RTB consists of two globular
domains, each divided into three homologous sub-domains (alpha, beta, gamma). In
this report, we describe five new murine IgG monoclonal antibodies (mAbs) against
RTB: MH3, 8A1, 8B3, LF1, and LC5. The mAbs have similar binding affinities (KD)
for ricin holotoxin, but displayed a wide range of in vitro toxin-neutralizing
activities. Competition ELISAs indicate that the two most potent toxin
neutralizing mAbs (MH3, 8A1), as well as one of the moderate toxin-neutralizing
mAbs (LF1), recognize distinct epitopes near the low affinity Gal recognition
domain in RTB subdomain 1alpha. Evaluated in a mouse model of systemic ricin
challenge, all five mAbs afforded some benefit against intoxication, but only MH3
was protective. However, neither MH3 nor 24B11, another well-characterized mAb
against RTB subdomain 1alpha, could passively protect mice against a mucosal
(intranasal) ricin challenge. This is in contrast to SylH3, a previously
characterized mAb directed against an epitope near RTB's high affinity Gal/GalNac
recognition element in sub-domain 2gamma, which protected animals against
systemic and mucosal ricin exposure. SylH3 was significantly more effective than
MH3 and 24B11 at blocking ricin attachment to host cell receptors, suggesting
that mucosal immunity to ricin is best imparted by antibodies that target RTB's
high affinity Gal/GalNac recognition element in subdomain 2gamma, not the low
affinity Gal recognition domain in subdomain 1alpha.
PMID- 28700746
TI - Antibacterial small molecules targeting the conserved TOPRIM domain of DNA
gyrase.
AB - To combat the threat of antibiotic-resistant Gram-negative bacteria, novel agents
that circumvent established resistance mechanisms are urgently needed. Our
approach was to focus first on identifying bioactive small molecules followed by
chemical lead prioritization and target identification. Within this annotated
library of bioactives, we identified a small molecule with activity against
efflux-deficient Escherichia coli and other sensitized Gram-negatives. Further
studies suggested that this compound inhibited DNA replication and selection for
resistance identified mutations in a subunit of E. coli DNA gyrase, a type II
topoisomerase. Our initial compound demonstrated weak inhibition of DNA gyrase
activity while optimized compounds demonstrated significantly improved inhibition
of E. coli and Pseudomonas aeruginosa DNA gyrase and caused cleaved complex
stabilization, a hallmark of certain bactericidal DNA gyrase inhibitors. Amino
acid substitutions conferring resistance to this new class of DNA gyrase
inhibitors reside exclusively in the TOPRIM domain of GyrB and are not associated
with resistance to the fluoroquinolones, suggesting a novel binding site for a
gyrase inhibitor.
PMID- 28700747
TI - The association between ethnicity and vaginal microbiota composition in
Amsterdam, the Netherlands.
AB - OBJECTIVE: To evaluate whether ethnicity is independently associated with vaginal
microbiota (VMB) composition in women living in Amsterdam, the Netherlands, as
has been shown for American women. METHODS: Women (18-34 years, non-pregnant, N =
610) representing the six largest ethnic groups (Dutch, African Surinamese, South
Asian Surinamese, Turkish, Moroccan, and Ghanaian) were sampled from the
population-based HELIUS study. Sampling was performed irrespective of health
status or healthcare seeking behavior. DNA was extracted from self-sampled
vaginal swabs and sequenced by Illumina MiSeq (16S rRNA gene V3-V4 region).
RESULTS: The overall prevalence of VMBs not dominated by lactobacilli was 38.5%:
32.2% had a VMB resembling bacterial vaginosis and another 6.2% had a VMB
dominated by Bifidobacteriaceae (not including Gardnerella vaginalis),
Corynebacterium, or pathobionts (streptococci, staphylococci, Proteus or
Enterobacteriaceae). The most prevalent VMB in ethnically Dutch women was a
Lactobacillus crispatus-dominated VMB, in African Surinamese and Ghanaian women a
polybacterial G. vaginalis-containing VMB, and in the other ethnic groups a L.
iners-dominated VMB. After adjustment for sociodemographic, behavioral and
clinical factors, African Surinamese ethnicity (adjusted odds ratio (aOR) 5.1,
95% confidence interval (CI) 2.1-12.0) and Ghanaian ethnicity (aOR 4.8, 95% CI
1.8-12.6) were associated with having a polybacterial G. vaginalis-containing
VMB, and African Surinamese ethnicity with a L. iners-dominated VMB (aOR 2.8, 95%
CI 1.2-6.2). Shorter steady relationship duration, inconsistent condom use with
casual partners, and not using hormonal contraception were also associated with
having a polybacterial G. vaginalis-containing VMB, but human papillomavirus
infection was not. Other sexually transmitted infections were uncommon.
CONCLUSIONS: The overall prevalence of having a VMB not dominated by lactobacilli
in this population-based cohort of women aged 18-34 years in Amsterdam was high
(38.5%), and women of sub-Saharan African descent were significantly more likely
to have a polybacterial G. vaginalis-containing VMB than Dutch women independent
of modifiable behaviors.
PMID- 28700749
TI - Correction: Adipocyte arrestin domain-containing 3 protein (Arrdc3) regulates
uncoupling protein 1 (Ucp1) expression in white adipose independently of
canonical changes in beta-adrenergic receptor signaling.
AB - [This corrects the article DOI: 10.1371/journal.pone.0173823.].
PMID- 28700748
TI - Hypoxia tolerance and responses to hypoxic stress during heart and skeletal
muscle inflammation in Atlantic salmon (Salmo salar).
AB - Heart and skeletal muscle inflammation (HSMI) is associated with Piscine
orthoreovirus (PRV) infection and is an important disease in Atlantic salmon
(Salmo salar) aquaculture. Since PRV infects erythrocytes and farmed salmon
frequently experience environmental hypoxia, the current study examined mutual
effects of PRV infection and hypoxia on pathogenesis and fish performance.
Furthermore, effects of HSMI on hypoxia tolerance, cardiorespiratory performance
and blood oxygen transport were studied. A cohabitation trial including PRV
infected post-smolts exposed to periodic hypoxic stress (4 h of 40% O2; PRV-H) at
4, 7 and 10 weeks post-infection (WPI) and infected fish reared under normoxic
conditions (PRV) was conducted. Periodic hypoxic stress did not influence
infection levels or histopathological changes in the heart. Individual incipient
lethal oxygen saturation (ILOS) was examined using a standardized hypoxia
challenge test (HCT). At 7 WPI, i.e. peak level of infection, both PRV and PRV-H
groups exhibited reduced hypoxia tolerance compared to non-infected fish. Three
weeks later (10 WPI), during peak levels of pathological changes, reduced hypoxia
tolerance was still observed for the PRV group while PRV-H performed equal to non
infected fish, implying a positive effect of the repeated exposure to hypoxic
stress. This was in line with maximum heart rate (fHmax) measurements, showing
equal performance of PRV-H and non-infected groups, but lower fHmax above 19
degrees C as well as lower temperature optimum (Topt) for aerobic scope for PRV,
suggesting reduced cardiac performance and thermal tolerance. In contrast, the
PRV-H group had reduced hemoglobin-oxygen affinity compared to non-infected fish.
In conclusion, Atlantic salmon suffering from HSMI have reduced hypoxia tolerance
and cardiac performance, which can be improved by preconditioning fish to
transient hypoxic stress episodes.
PMID- 28700750
TI - Correction: Genotypic and phenotypic diversity of Lactobacillus rhamnosus
clinical isolates, their comparison with strain GG and their recognition by
complement system.
AB - [This corrects the article DOI: 10.1371/journal.pone.0176739.].
PMID- 28700751
TI - A high seroprevalence of antibodies to pertussis toxin among Japanese adults:
Qualitative and quantitative analyses.
AB - In 2013, national serosurveillance detected a high seroprevalence of antibodies
to pertussis toxin (PT) from Bordetella pertussis among Japanese adults. Thus, we
aimed to determine the cause(s) of this high seroprevalence, and analyzed the
titers of antibodies to PT and filamentous hemagglutinin (FHA) among adults (35
44 years old), young children (4-7 years old), and older children (10-14 years
old). Our quantitative analyses revealed that adults had higher seroprevalences
of anti-PT IgG and PT-neutralizing antibodies, and similar titers of anti-FHA
IgG, compared to the young and older children. Positive correlations were
observed between the titers of PT-neutralizing antibodies and anti-PT IgG in all
age groups (rs values of 0.326-0.522), although the correlation tended to
decrease with age. The ratio of PT-neutralizing antibodies to anti-PT IgG was
significantly different when we compared the serum and purified IgG fractions
among adults (p = 0.016), although this result was not observed among young and
older children. Thus, it appears that some adults had non-IgG immunoglobulins to
PT. Our analyses also revealed that adults had high-avidity anti-PT IgG (avidity
index: 63.5%, similar results were observed among the children); however, the
adults had lower-avidity anti-FHA IgG (37.9%, p < 0.05). It is possible that low
avidity anti-FHA IgG is related to infection with other respiratory pathogens
(e.g., Bordetella parapertussis, Haemophilus influenzae, or Mycoplasma
pneumoniae), which produces antibodies to FHA-like proteins. Our observations
suggest that these adults had been infected with B. pertussis and other
pathogen(s) during their adulthood.
PMID- 28700752
TI - Role of a novel immune modulating DDR2-expressing population in silica-induced
pulmonary fibrosis.
AB - Micro-injuries associated with chronic inhaled particle exposures are linked with
activation of the immune response and are thought to contribute to progression of
fibrotic disease. In the pulmonary environment, we have previously demonstrated a
heterogeneous population of circulating fibroblast precursors (CFPs), which are
defined by expression of the pan-leukocyte marker CD45 and the collagen receptor,
discoidin domain receptor-2 (DDR2). This population is derived from the
hematopoietic stem cell, expresses collagen, and has a fibroblastic morphology in
vitro. Herein, we demonstrate a novel subset of CFPs expressing immune markers
CD11b, CD11c, and major histocompatibility complex II (MHC II). The CFP
population was skewed toward this immune marker expressing subset in animals with
silica-induced pulmonary fibrosis. Data indicate that this CFP subset upregulates
co-stimulatory molecules and MHC II expression in response to silica-induced
fibrosis in vivo. Functionally, this population was shown to promote T cell
skewing away from a Th1 response and toward a pro-inflammatory profile. These
studies represent the first direct flow cytometric and functional evaluation of
the novel immune marker expressing CFP subset in an exposure-induced model of
pulmonary fibrosis. Elucidating the role of this CFP subset may enhance our
understanding of the complex immune balance critical to mediating exposures at
the pulmonary-host interface and may be a valuable target for the treatment of
exposure-induced pulmonary fibrosis.
PMID- 28700753
TI - Acute kidney injury after cardiac surgery is associated with mid-term but not
long-term mortality: A cohort-based study.
AB - Acute kidney injury (AKI) in cardiac surgery is associated with complications,
early and late mortality and increased health care expenditures. The overall
dynamic comorbidity-adjusted contributions of an episode of AKI on mortality
during long-term follow-up have not been fully explored. A longitudinal cohort of
7075 adult patients admitted for cardiac surgery were enrolled in the study.
Follow-up data were obtained through telephonic survey after 1, 5, 10, and 15
years or from the National Mortality Registry. All-cause mortality was assessed
at five time intervals: I) 30 days after surgery to 1 year; II) 1 to 3 years;
III) 3 to 5 years; IV) 5 to 10 years; and V) 10 to 15 years. For the adjustment
of mortality for comorbidity and pre-, intra- and postoperative variables, Cox
proportional hazard regression models were conducted within each period. The
overall incidence of AKI was 36.1%. AKI was an independent predictor of death
only during the first five years after surgery (30 days to 1 year: HR 1.834, 95%
CI 1.459 to 2.306; 1 to 3 years: HR 1.285, 95% CI 1.023 to 1.610; and 3 to five
years: HR 1.330, 95% CI 1.123 to 1.750). Only age, diabetes mellitus and CHF were
associated with increased risk of death over the entire follow-up period. Our
study demonstrates a transient association of AKI with long-term mortality that
progressively decreases and vanishes five years after surgery. The knowledge of
this dynamic is crucial to understanding this complex association, planning
health care and allocating resources.
PMID- 28700754
TI - Promotion of physical activity interventions for community dwelling older adults:
A systematic review of reviews.
AB - OBJECTIVES: While there is strong evidence that regular participation in physical
activity (PA) brings numerous health benefits to older adults, and interventions
to effectively promote PA are being developed and tested, the characteristics and
components of the most effective interventions remain unclear. This
systematically conducted review of systematic reviews evaluated the effects and
characteristics of PA promotion interventions aimed at community dwelling people
over 50 years old. METHODS: Major databases were searched for reviews from
January 1990 to May 2015. TIDieR guidelines aided data extraction and the ROBIS
tool was used to assess the risk of bias. Primary outcomes were objective and
self-reported levels of PA. Indicators of psychological wellbeing and
participation rates were secondary outcomes. RESULTS: Of 1284 records identified,
19 reviews met inclusion criteria and eight included meta-analyses. Interventions
typically incorporated behaviour change techniques (BCTs) and were delivered as
face-to-face, remote, group, individual or as combined interventions. Despite
their heterogeneity, interventions often resulted in sustained improvements in PA
over the study period, typically at 12 months, and led to improvements in general
wellbeing. However, ways to ensure effective maintenance beyond one year are
unclear. Certain intervention components were more clearly associated with
positive effects (e.g. tailoring promotion strategy with combination of cognitive
and behavioural elements, low to moderate intensity activity recommended). We
found no evidence that certain other intervention characteristics were superior
in achieving positive outcomes (e.g. mode of delivery, setting, professional
background of the intervention provider, type of PA recommended). CONCLUSION: The
evidence suggests that interventions to promote PA among older adults are
generally effective but there is uncertainty around the most beneficial
intervention components. There are indications that purely cognitive strategies
and BCTs might be less suitable for older adults than motivators more meaningful
to them, including social and environmental support, and enjoyment coming from
being physically active. A whole system-oriented approach is required that is
tailored to meet the needs of older adults and aligned with social, individual
and environmental factors.
PMID- 28700755
TI - The dead seed coat functions as a long-term storage for active hydrolytic
enzymes.
AB - Seed development culminates in programmed cell death (PCD) and hardening of
organs enclosing the embryo (e.g., pericarp, seed coat) providing essentially a
physical shield for protection during storage in the soil. We examined the
proposal that dead organs enclosing embryos are unique entities that store and
release upon hydration active proteins that might increase seed persistence in
soil, germination and seedling establishment. Proteome analyses of dead seed
coats of Brassicaceae species revealed hundreds of proteins being stored in the
seed coat and released upon hydration, many are stress-associated proteins such
as nucleases, proteases and chitinases. Functional analysis revealed that dead
seed coats function as long-term storage for multiple active hydrolytic enzymes
(e.g., nucleases) that can persist in active forms for decades. Substances
released from the dead seed coat of the annual desert plant Anastatica
hierochuntica displayed strong antimicrobial activity. Our data highlighted a
previously unrecognized feature of dead organs enclosing embryos (e.g., seed
coat) functioning not only as a physical shield for embryo protection but also as
a long-term storage for active proteins and other substances that are released
upon hydration to the "seedsphere" and could contribute to seed persistence in
the soil, germination and seedling establishment.
PMID- 28700756
TI - Rewriting the script on polypharmacy.
AB - With a blood pressure consistently around 105/50 mm Hg, it was an easy decision
to stop one of the patient's 3 antihypertensive medications.
PMID- 28700757
TI - Stroke: Secondary prevention of ischemic events.
AB - A multifactorial approach is key to effective secondary stroke prevention. Here's
how to individualize your plan for your at-risk patients.
PMID- 28700758
TI - Deprescribing: A simple method for reducing polypharmacy.
AB - Polypharmacy brings with it increased risks for adverse drug events and reduced
functional capacity. This 4-step plan will help you safely deprescribe in older
adults.
PMID- 28700759
TI - Elevated levels of AST, ALT, and CPK . no family history of liver disease . Dx?
AB - A 26-year-old healthy male veteran with bipolar disorder and post-traumatic
stress disorder was referred for a gastroenterology consultation after a routine
laboratory evaluation revealed elevated levels of aspartate aminotransferase,
1040 IU/L (normal range, 10-40 IU/L), and alanine aminotransferase, 334 IU/L
(normal range, 7-56 IU/L). He had been taking divalproex and ziprasidone for the
previous 2 years, during which time liver test results had been normal.
PMID- 28700760
TI - PURLs: Which combined OC to prescribe with CV safety in mind?
AB - With various formulations available, which combined OC should you recommend to
minimize not only the risk of PE, but also the risk of stroke and MI?
PMID- 28700761
TI - Measles: Why it's still a threat.
AB - A recent outbreak in Minnesota underscores the need to maintain vigilance and
adhere to best practices in immunization and containment of known cases.
PMID- 28700762
TI - Clinical Inquiry: What effects--if any--does marijuana use during pregnancy have
on the fetus or child?
AB - The effects are unclear. Marijuana use during pregnancy is associated with
clinically unimportant lower birth weights (growth differences of approximately
100 g), but no differences in preterm births or congenital anomalies.
PMID- 28700763
TI - Recalcitrant genital papules.
AB - This patient was initially told he had genital warts, but the appearance of the
lesions, and the presence of a rash on his trunk and extremities, suggested
another diagnosis.
PMID- 28700765
TI - Gradual vs abrupt smoking cessation: Each has its place.
PMID- 28700764
TI - A sheep in wolf's clothing?
AB - A 25-year-old college student with no medical history sought care at our hospital
for a nonproductive cough, subjective fevers, myalgia, and malaise that he'd
developed 10 days earlier. The day before his visit, he'd also developed scratchy
red eyes and a sore throat. He said he'd taken an over-the-counter cough
suppressant to help with the cough, but his eyes and lips developed further
redness and irritation. On examination, the patient demonstrated conjunctival
suffusion, periorbital edema, diffuse oral stomatitis with pseudomembranous
crusting, and nasal crusting. His vital signs were within normal limits, and he
had no epithelial skin eruptions or erosions in any other mucosal regions. What's
your diagnosis?
PMID- 28700766
TI - Consider this probiotic for functional abdominal pain.
PMID- 28700767
TI - Effect of non-insulin-based glucose-lowering therapies on cardiovascular outcomes
in patients with type 2 diabetes.
AB - Current guidelines for the treatment of patients with diabetes are focused on
improving glycemic control and treating appropriate cardiovascular (CV) risk
factors. Basic recommendations include blood pressure management with a goal of
<140 mm Hg systolic pressure, statin therapy in all patients >=40 years of age
with diabetes (moderate intensity for all, and high intensity if at high risk of
CVD events), and aspirin therapy in all adults at increased CV risk (10-year risk
of CVD events >10%). Oral antihyperglycemic medications remain the cornerstone of
treatment for optimizing glucose control in patients with diabetes. In this
review, we aim to present the basic mechanisms for each class of commonly used
non-insulin-based glucose-lowering drugs and to discuss the effect of these
medications on CV events.
PMID- 28700772
TI - Ketamine for the Treatment of Depression-Reply.
PMID- 28700773
TI - Association of Multiple Primary Skin Cancers With Human Immunodeficiency Virus
Infection, CD4 Count, and Viral Load.
AB - Importance: Persons with human immunodeficiency virus (HIV) have a 2.8-fold
higher risk than HIV-uninfected persons of nonmelanoma skin cancer (NMSC),
defined as basal cell carcinoma (BCC) and squamous cell carcinoma (SCC).
Individuals with a prior NMSC history are at increased risk for subsequent NMSC,
but the magnitude of risk and its relation to HIV disease-related factors,
including CD4 count and viral load (VL), are unknown. Objective: To better
understand how laboratory markers currently used to evaluate HIV disease
progression may be associated with subsequent NMSC risk. Design, Setting, and
Participants: This cohort study analyzed 455 HIV-infected and 1945 HIV-uninfected
patients, all of them members of the Kaiser Permanente Northern California (KPNC)
health care plan, diagnosed with at least 1 NMSC from 1996-2008 to determine risk
of subsequent NMSCs in relation to CD4 count and VL. All participants were white,
non-Hispanic persons 18 years or older who had had at least 1 NMSC during the
1996-2008 period. Participants entered the cohort at their first NMSC diagnosis
and were observed through 2008. Incidence rates were calculated and adjusted
hazard ratios were estimated using extended Cox regression models with recent CD4
count and VL analyzed as time-changing covariates. Main Outcomes and Measures:
Measured CD4 count, VL, and subsequent NMSC (BCC and SCC). Results: The cohort
comprised 455 HIV-infected participants (13 [3%] women) and 1952 HIV-uninfected
participants (154 [8%] women). Median duration of observation was 4.6 years, and
16.5% (n = 390) either died (n = 35) or lost KPNC membership status (n = 355)
without having a subsequent primary NMSC. Compared with HIV-uninfected persons,
HIV-infected individuals were slightly younger (mean age, 52.5 vs 55.5 years),
more likely men (97% vs 92%), more likely to have smoked (57% vs 45%), and less
likely to be overweight/obese (50% vs 61%). The small observed differences by HIV
status in matching characteristics (ie, age and sex) resulted from the
restriction of the original cohort to those with at least 1 NMSC. Compared with
uninfected individuals, those with HIV infection with a recent biomarker of more
severe immune deficiency (CD4 count <200 cells/mL) had a 44% increased risk of
subsequent NMSC overall and a 222% increase risk of SCC in particular, suggesting
that subsequent SCC risk is associated with immune dysfunction. Conclusions and
Relevance: HIV-infected persons compared with HIV-uninfected persons were are at
higher risk for subsequent new SCC but not BCC, with a dose-response relationship
between risk and lower CD4 counts and higher VLs. Subsequent new primary SCCs had
a strong association with lower CD4 and higher VL among HIV-infected persons,
suggesting that immune dysfunction might contribute to increased SCC risk.
Clinical implications include targeted monitoring for SCC among HIV-infected
individuals, particularly those with low CD4 counts or high VLs.
PMID- 28700774
TI - A Unique Program to Incorporate Volunteers Into a Nationwide Emergency Medical
System: Maximizing Preparedness for a Mass Casualty Incident.
PMID- 28700775
TI - Improving Care in an Accountable Care Organization: So Many Choices, So Little
Time.
PMID- 28700776
TI - The Linear Nail Streak: A Lesson in Cultural Humility.
PMID- 28700777
TI - Ketamine for the Treatment of Depression.
PMID- 28700778
TI - Frequent GNAQ, GNA11, and EIF1AX Mutations in Iris Melanoma.
AB - Purpose: The most common malignant intraocular tumors with a high mortality in
adults are uveal melanomas. Uveal melanomas arise most frequently in the choroid
or ciliary body (97%) and rarely in the iris (3%). Whereas conjunctival and
posterior uveal (ciliary body and choroidal) melanomas have been studied in more
detail genetically, little data exist regarding iris melanomas. Methods: In our
study, we genetically analyzed 19 iris melanomas, 8 ciliary body melanomas, 3
ring melanomas, and 4 iris nevi. A targeted next-generation sequencing approach
was applied, covering the mutational hotspot regions of nine genes known to be
mutated in conjunctival and uveal melanoma (BRAF, NRAS, KIT, GNAQ, GNA11,
CYSLTR2, SF3B1, EIF1AX, and BAP1). Results: Activating GNAQ or GNA11 hotspot
mutations were detected in a mutually exclusive fashion in 84% (16/19) of iris
melanomas. EIF1AX gene mutations also were frequent, detected in 42% (8/19) of
iris melanomas. In 4 iris nevi, one GNAQ mutation was identified. GNAQ, GNA11,
EIF1AX, and BAP1 mutations were identified at varying frequencies in ciliary body
and ring melanomas. Conclusions: In this most comprehensive genetic analysis of
iris melanomas published to date, we find iris melanomas to be related
genetically to choroidal and ciliary body melanomas, frequently harboring GNAQ,
GNA11, and EIF1AX mutations. Future studies will need to assess if screening
mutation profiles in iris melanomas may be of diagnostic or prognostic value.
PMID- 28700779
TI - Corneal Wound Repair After Rose Bengal and Green Light Crosslinking: Clinical and
Histologic Study.
AB - Purpose: To evaluate corneal wound healing after treatment with a new collagen
crosslinking protocol using rose bengal dye and green light (RGX). Methods: One
cornea of 20 New Zealand rabbits was de-epithelialized (DE) in an 8-mm diameter
circle and, in another group (n = 25), the DE corneas were then stained with 0.1%
rose bengal for 2 minutes and exposed to green light (532 nm) for 7 minutes
(RGX). The contralateral eyes without treatment acted as controls. The animals
were clinically followed including fluorescein staining and pachymetry. Healing
events were analyzed after euthanasia at 2, 30, and 60 days. Cell death (TUNEL
assay), cell proliferation (5-bromo-2'-deoxyuridine incorporation), and cell
differentiation to myofibroblasts (alpha-SMA labeling) were carried out. In
addition, loss of keratocytes and subsequent repopulation of the corneal stroma
were quantified on hematoxylin-eosin-stained sections. Results: Wound closure was
slower after RGX (4.4 days) then after DE (3.3 days). Cell death was restricted
to the anterior central stroma, and the cellular decrease did not differ
significantly between RGX and DE corneas. Cell proliferation in the epithelium
and stroma appeared at 2 days. In both DE and RGX corneas, recovery of the
epithelium was complete at day 30, although cell repopulation of the stroma was
not complete at 60 days. Conclusions: The healing response in corneas after RGX
is very similar to that observed after DE alone, suggesting that, along with its
short treatment time and limited effect on keratocytes, RGX displays good
potential for clinical cornea stiffening.
PMID- 28700780
TI - Distinction of Risk Factors for Superficial vs Organ-Space Surgical Site
Infections After Pancreatic Surgery.
AB - Importance: Surgical site infection (SSI) rates are increasingly used as a
quality metric. However, risk factors for SSI in pancreatic surgery remain
undefined. Objective: To stratify superficial and organ-space SSIs after
pancreatectomy and investigate their modifiable risk factors. Design, Setting,
and Participants: This retrospective analysis included 201 patients undergoing
pancreatic surgery at a university-based tertiary referral center from July 1,
2013, through June 30, 2015, and 10 371 patients from National Surgical Quality
Improvement Program-Hepatopancreaticobiliary (NSQIP-HPB) Collaborative sites from
January 1, 2014, through December 31, 2015. Main Outcomes and Measures:
Superficial, deep-incisional, and organ-space SSIs, as defined by NSQIP. Results:
Among the 201 patients treated at the single center (108 men [53.7%] and 93 women
[46.3%]; median age, 48.6 years [IQR, 41.4-57.3 years]), 58 had any SSI (28.9%);
28 (13.9%), superficial SSI; 8 (4%), deep-incisional SSI; and 24 (11.9%), organ
space SSI. Independent risk factors for superficial SSI were preoperative biliary
stenting (odds ratio [OR], 4.81; 95% CI, 1.25-18.56; P = .02) and use of
immunosuppressive corticosteroids (OR, 13.42; 95% CI, 1.64-109.72; P = .02),
whereas soft gland texture was the only risk factor for organ-space SSI (OR,
4.45; 95% CI, 1.35-14.66; P = .01). Most patients with organ-space infections
also had grades B/C fistulae (15 of 24 [62.5%] vs 4 of 143 [2.8%] in patients
with no SSI; P < .001). Organ/space but not superficial SSI was associated with
an increased rate of sepsis (7 of 24 [29.2%] vs 4 of 143 [2.8%]; P < .001) and
prolonged length of hospital stay (12 vs 8 days; P = .04). Among patients in the
NSQIP-HPB Collaborative, 2057 (19.8%) had any SSI; 719 (6.9%), superficial SSI;
207 (2%), deep-incisional SSI; and 1287 (12.4%), organ-space SSI. Preoperative
biliary stenting was confirmed as an independent risk factor for superficial SSI
(OR, 2.07; 95% CI, 1.58-2.71; P < .001). In this larger data set, soft gland
texture was an independent risk factor for superficial SSI (OR, 1.45; 95% CI,
1.14-1.85; P = .002) but was more strongly and significantly associated with
organ-space SSI (OR, 2.32; 95% CI, 1.88-2.85; P < .001). Conclusions and
Relevance: Preoperative biliary stenting and coriticosteroid use increase
superficial SSI, even in patients receiving perioperative piperacillin
tazobactam. Additional measures, including extended broad-spectrum perioperative
antibiotic treatment, should be considered in these patients. Organ/space SSIs
appear to be related to pancreatic fistulae, which are not modifiable. Reporting
these different subtypes as a single, overall rate may be misleading.
PMID- 28700781
TI - Efficacy and Safety of Spironolactone in Acute Heart Failure: The ATHENA-HF
Randomized Clinical Trial.
AB - Importance: Persistent congestion is associated with worse outcomes in acute
heart failure (AHF). Mineralocorticoid receptor antagonists administered at high
doses may relieve congestion, overcome diuretic resistance, and mitigate the
effects of adverse neurohormonal activation in AHF. Objective: To assess the
effect of high-dose spironolactone and usual care on N-terminal pro-B-type
natriuretic peptide (NT-proBNP) levels compared with usual care alone. Design,
Setting, and Participants: This double-blind and placebo (or low-dose)-controlled
randomized clinical trial was conducted in 22 US acute care hospitals among
patients with AHF who were previously receiving no or low-dose (12.5 mg or 25 mg
daily) spironolactone and had NT-proBNP levels of 1000 pg/mL or more or B-type
natriuretic peptide levels of 250 pg/mL or more, regardless of ejection fraction.
Interventions: High-dose spironolactone (100 mg) vs placebo or 25 mg
spironolactone (usual care) daily for 96 hours. Main Outcomes and Measures: The
primary end point was the change in NT-proBNP levels from baseline to 96 hours.
Secondary end points included the clinical congestion score, dyspnea assessment,
net urine output, and net weight change. Safety end points included hyperkalemia
and changes in renal function. Results: A total of 360 patients were randomized,
of whom the median age was 65 years, 129 (36%) were women, 200 (55.5%) were
white, 151 (42%) were black, 8 (2%) were Hispanic or Latino, 9 (2.5%) were of
other race/ethnicity, and the median left ventricular ejection fraction was 34%.
Baseline median (interquartile range) NT-proBNP levels were 4601 (2697-9596)
pg/mL among the group treated with high-dose spironolactone and 3753 (1968-7633)
pg/mL among the group who received usual care. There was no significant
difference in the log NT-proBNP reduction between the 2 groups (-0.55 [95% CI,
0.92 to -0.18] with high-dose spironolactone and -0.49 [95% CI, -0.98 to -0.14]
with usual care, P = .57). None of the secondary end point or day-30 all-cause
mortality or heart failure hospitalization rate differed between the 2 groups.
The changes in serum potassium and estimated glomerular filtration rate at 24,
48, 72, and 96 hours. were similar between the 2 groups. Conclusions and
Relevance: Adding treatment with high-dose spironolactone to usual care for
patients with AHF for 96 hours was well tolerated but did not improve the primary
or secondary efficacy end points. Trial Registration: clinicaltrials.gov
Identifier: NCT02235077.
PMID- 28700782
TI - Ketamine for the Treatment of Depression.
PMID- 28700783
TI - A Unique Program to Incorporate Volunteers Into a Nationwide Emergency Medical
System-Reply.
PMID- 28700785
TI - The "Quality Minute"-A New, Brief, and Structured Technique for Quality
Improvement Education During the Morbidity and Mortality Conference.
PMID- 28700784
TI - Association of Clinical Factors With a Major Pathologic Response Following
Preoperative Therapy for Pancreatic Ductal Adenocarcinoma.
AB - Importance: We previously demonstrated that a major pathologic response to
preoperative therapy, defined histopathologically by the presence of less than 5%
viable cancer cells in the surgical specimen, is an important prognostic factor
for patients with pancreatic ductal adenocarcinoma. However, to our knowledge,
the patients most likely to experience a significant response to therapy are
undefined. Objective: To identify clinical factors associated with major
pathologic response in a large cohort of patients who underwent preoperative
therapy and pancreatectomy for pancreatic ductal adenocarcinoma. Design, Setting,
and Participants: Retrospective review of a prospectively maintained database at
University of Texas MD Anderson Cancer Center. The study included 583 patients
with histopathologically confirmed pancreatic ductal adenocarcinoma who received
preoperative therapy prior to pancreatectomy between 1990 and 2015. Exposures:
Preoperative therapy consisted of systemic chemotherapy alone (n = 38; 6.5%),
chemoradiation alone (n = 261; 44.8%), or both (n = 284; 48.7%) prior to
pancreatoduodenectomy (n = 514; 88.2%), distal pancreatectomy (n = 62; 10.6%), or
total pancreatectomy (n = 7; 1.2%). Main Outcomes and Measures: Clinical
variables associated with a major pathologic response (pathologic complete
response or <5% residual cancer cells) were evaluated using logistic regression.
Results: Among all patients, the mean (SD) age was 63.7 (9.2) years, and 53.0%
were men. A major pathologic response was seen in 77 patients (13.2%) including
23 (3.9%) who had a complete pathologic response. The median overall survival
duration was significantly longer for patients who had a major response than for
those who did not (73.4 months vs 32.2 months, P < .001). On multivariate
logistic regression, only age younger than 50 years, baseline serum cancer
antigen 19-9 level less than 200 U/mL, and gemcitabine as a radiosensitizer were
associated with a major response. The number of these positive factors was
associated with the likelihood of a major response in a stepwise fashion (0,
7.5%; 1, 12.7%; 2, 16.9%; 3, 35.7%; P = .009). Conclusions and Relevance:
Although a major pathologic response occurs infrequently following preoperative
therapy for pancreatic ductal adenocarcinoma, it is associated with a
significantly improved prognosis. Of the patient- and treatment-related factors
we analyzed, only young age, low baseline cancer antigen 19-9, and gemcitabine as
a radiosensitizer were associated with a major pathologic response. Given its
association with long-term survival, better predictors of response and more
effective preoperative regimens should be aggressively sought.
PMID- 28700786
TI - Neoadjuvant Treatment in Locally Advanced and Borderline Resectable Pancreatic
Cancer vs Primary Resectable Pancreatic Cancer.
PMID- 28700787
TI - A Young Woman With a New Breast Mass.
PMID- 28700788
TI - Optimal Medical Therapy for Known Coronary Artery Disease: A Review.
AB - Importance: This review examines the current state-of-the-art optimal medical
therapy (OMT) for patients with known coronary artery disease. This therapy,
which is sometimes labeled as secondary prevention, is effective in preventing
recurrent events and is recommended by the American College of Cardiology
Foundation/American Heart Association guidelines. Optimal medical therapy is of
recognized public health benefit. Observations: The available evidence from broad
patient populations, contemporary randomized trials, and multiple recent studies
with pharmacy records indicates that the delivery of OMT is far from ideal. We
suggest approaches for quality improvement, including better patient education,
the increased use of interventions that are known to improve compliance, and the
use of performance measures focused on long-term OMT in outpatient care.
Conclusions and Relevance: Improvement in the delivery of OMT to patients with
coronary artery disease is one possible step to help the United States reduce the
recently reported increase in death rate from heart disease.
PMID- 28700789
TI - Hair Repigmentation During Immunotherapy Treatment With an Anti-Programmed Cell
Death 1 and Anti-Programmed Cell Death Ligand 1 Agent for Lung Cancer.
AB - Importance: New targeted therapies for cancer have been released in recent years,
opening new horizons in the treatment of patients with cancer. However, their
related adverse events (AE) are not fully characterized. Hair repigmentation (HR)
is a nondescribed effect secondary to anti-programmed cell death 1 (anti-PD-1)
and anti-programmed cell death ligand 1 (anti-PD-L1 ) therapy for treatment of
lung cancer (LC), in opposition to the vitiligo reactions that develop during
melanoma treatment. Objective: To describe a new adverse event occurring during
anti-PD-1/anti-PD-L1 therapy for LC. Design, Setting, and Participants: A case
series from a descriptive observation of 14 patients with HR after anti-PD-1/anti
PD-L1 treatment, recruited between September and December, 2016, who were
followed up to detect whether they developed cutaneous AE at the time HR was
detected. The patients had all been treated in the dermatology department at
Hospital Universitari Germans Trias i Pujol, Badalona, Spain. Main Outcomes and
Measures: Clinical observation of HR during anti-PD-1/anti-PD-L1 therapy for LC,
proved by comparing old pictures provided by the patients and recent pictures
taken during the follow-up. Results: Fourteen patients (13 men and 1 woman; mean
age, 64.9 years) receiving anti-PD-1 or anti-PD-L1 therapy for non-small-cell
lung cancer (NSCLC) presented hair repigmentation during follow-up. This hair
repigmentation consisted in a diffuse darkening of the hair in 13 of 14 patients,
or in black patches between white hairs in 1. Thirteen of 14 patients presented a
good clinical response to the treatment, with at least stable disease, and only 1
had to stop the therapy after only 4 cycles of treatment owing to a life
threatening progression of the disease. Conclusions and Relevance: We present to
our knowledge the first report of hair repigmentation owing to anti-PD-1/anti-PD
L1 therapy for lung cancer in a series of 14 patients. Hair repigmentation may be
a good response marker in patients receiving anti-PD1/anti-PD-L1 therapy for LC.
PMID- 28700790
TI - Association of Changes in Medication Use and Adherence With Accountable Care
Organization Exposure in Patients With Cardiovascular Disease or Diabetes.
AB - Importance: Many of the quality measures used to assess accountable care
organization (ACO) performance in the Medicare Shared Savings Program (MSSP)
focus on disease control and medication use among patients with cardiovascular
disease and diabetes. To date, the association between participation in the MSSP
by provider organizations and medication use or adherence among their patients
with cardiovascular disease or diabetes has not been described. Objective: To
assess the association between exposure to the MSSP and changes in the use of and
adherence to common antihypertensive, lipid-lowering, and hypoglycemic
medications. Design, Setting, and Participants: Fee-for-service Medicare claims
from January 1, 2009, to December 31, 2014, were used to conduct difference-in
differences comparisons of changes for ACO-attributed beneficiaries from before
the start of ACO contracts to 2014 with concurrent changes for beneficiaries
attributed to local non-ACO providers (control group). A random 20% sample of
Medicare beneficiaries contributing 4 482 168 to 10 849 224 beneficiary-years for
analysis from 2009 to 2014, depending on the drug class, was examined.
Differential changes were estimated separately for cohorts of ACOs entering the
MSSP in 2012, 2013, and 2014. Data analysis was conducted from November 1, 2016,
to April 5, 2017. Exposures: Patient attribution to an ACO after entry into the
MSSP. Main Outcomes and Measures: Any use (at least 1 prescription fill) and
proportion of days covered (PDC), a standard claims-based measure of adherence,
assessed for each of 6 drug classes: statins, angiotensin-converting enzyme
inhibitors and angiotensin II receptor blockers, beta-blockers, thiazide
diuretics, calcium channel blockers, and metformin. Results: Differences in
patient characteristics between the MSSP and control group were generally small
after geographic adjustment and changed minimally from the precontract period to
2014. There were no significant differential changes in medication use from the
precontract period to 2014 for any cohort of MSSP ACOs in any drug class, except
for a slight differential increase in the use of thiazides among beneficiaries
with hypertension in the 2013 entry cohort (adjusted differential change, 0.5
percentage point; 95% CI, 0.1-0.8 percentage points; or 1.5% of the overall
percentage using thiazides [33.4%], P = .01). Similarly, there were no
significant differential changes in PDC among beneficiaries with at least 1
prescription fill, except for slight differential increases in the PDC for beta
blockers in the 2012 entry cohort (adjusted differential change, 0.3 percentage
point; 95% CI, 0.1-0.5 percentage points; or 0.4% of the mean PDC [82.3%], P =
.003) and for metformin in the 2012 and 2013 cohorts (adjusted differential
change, 0.5 percentage point; 95% CI, 0.1-0.9 percentage points; or 0.6% of the
mean PDC [78.2%], P = .01 for both). Conclusions and Relevance: Exposure to the
MSSP has not been associated with meaningful changes in medication use or
adherence among patients with cardiovascular disease and diabetes.
PMID- 28700792
TI - Association of Ibrutinib Treatment With Bleeding Complications in Cutaneous
Surgery.
PMID- 28700791
TI - Efficacy of Tramadol Extended-Release for Opioid Withdrawal: A Randomized
Clinical Trial.
AB - Importance: Opioid use disorder (OUD) is a significant public health problem.
Supervised withdrawal (ie, detoxification) from opioids using clonidine or
buprenorphine hydrochloride is a widely used treatment. Objective: To evaluate
whether tramadol hydrochloride extended-release (ER), an approved analgesic with
opioid and nonopioid mechanisms of action and low abuse potential, is effective
for use in supervised withdrawal settings. Design, Setting, and Participants: A
randomized clinical trial was conducted in a residential research setting with
103 participants with OUD. Participants' treatment was stabilized with morphine,
30 mg, administered subcutaneously 4 times daily. A 7-day taper using clonidine
(n = 36), tramadol ER (n = 36), or buprenorphine (n = 31) was then instituted,
and patients were crossed-over to double-blind placebo during a post-taper
period. The study was conducted from October 25, 2010, to June 23, 2015. Main
Outcomes and Measures: Retention, withdrawal symptom management, concomitant
medication utilization, and naltrexone induction. Results were analyzed over time
and using area under the curve for the intention-to-treat and completer groups.
Results: Of the 103 participants, 88 (85.4%) were men and 43 (41.7%) were white;
mean (SD) age was 28.9 (10.4) years. Buprenorphine participants (28 [90.3%]) were
significantly more likely to be retained at the end of the taper compared with
clonidine participants (22 [61.1%]); tramadol ER retention was intermediate and
did not differ significantly from that of the other groups (26 [72.2%]; chi2 =
8.5, P = .01). Time-course analyses of withdrawal revealed significant effects of
phase (taper, post taper) for the Clinical Opiate Withdrawal Scale (COWS) score
(taper mean, 5.19 [SE, .26]; post-taper mean, 3.97 [SE, .23]; F2,170 = 3.6, P =
.03) and Subjective Opiate Withdrawal Scale (SOWS) score (taper mean,8.81 [SE,
.40]; post-taper mean, 4.14 [SE, .30]; F2,170 = 15.7, P < .001), but no group
effects or group * phase interactions. Analyses of area under the curve of SOWS
total scores showed significant reductions (F2,159 = 17.7, P < .001) in
withdrawal severity between the taper and post-taper periods for clonidine (taper
mean, 13.1; post-taper mean, 3.2; P < .001) and tramadol ER (taper mean, 7.4;
post-taper mean, 2.8; P = .03), but not buprenorphine (taper mean, 6.4; post
taper mean, 7.4). Use of concomitant medication increased significantly (F2,159 =
30.7, P < .001) from stabilization to taper in the clonidine (stabilization
mean, 0.64 [SE, .05]; taper mean, 1.54 [SE, .10]; P < .001) and tramadol ER
(stabilization mean, 0.53 [SE, .05]; taper mean, 1.19 [SE, .09]; P = .003) groups
and from stabilization to post taper in the buprenorphine group (stabilization
mean, 0.46 [SE, .05] post-taper mean, 1.17 [SE, .09]; P = .006), suggesting
higher withdrawal for those groups during those periods. Naltrexone initiation
was voluntary and the percentage of participants choosing naltrexone therapy
within the clonidine (8 [22.2%]), tramadol ER (7 [19.4%]), or buprenorphine (3
[9.7%]) groups did not differ significantly (chi2 = 2.5, P = .29). Conclusions
and Relevance: The results of this trial suggest that tramadol ER is more
effective than clonidine and comparable to buprenorphine in reducing opioid
withdrawal symptoms during a residential tapering program. Data support further
examination of tramadol ER as a method to manage opioid withdrawal symptoms.
Trial Registration: Clinicaltrials.gov Identifier: NCT01188421.
PMID- 28700795
TI - Henry Radcliffe Crocker-From the Elephant Man to the Textbook.
PMID- 28700793
TI - Pilot Programs Seek to Integrate Genomic Data Into Practice.
PMID- 28700796
TI - Snails and Skin Care-An Uncovered Combination.
PMID- 28700797
TI - Consider the Monobrow.
PMID- 28700798
TI - The Cutaneous Cancer of Ferdinando Orsini, 5th Duke of Gravina.
PMID- 28700799
TI - The Evolving Nomenclature of Erythema Ab Igne-Redness From Fire.
PMID- 28700800
TI - Tivadar Kosztka Csontvary's The Old Fisherman-A Remarkable Example of
Photodamaged Skin in Art.
PMID- 28700802
TI - Ketamine for the Treatment of Depression.
PMID- 28700803
TI - Factors Associated With Underestimation of Invasive Cancer in Patients With
Ductal Carcinoma In Situ: Precautions for Active Surveillance.
AB - Importance: Recent recognition of the overdiagnosis and overtreatment of ductal
carcinoma in situ (DCIS) detected by mammography has led to the development of
clinical trials randomizing women with non-high-grade DCIS to active
surveillance, defined as imaging surveillance with or without endocrine therapy,
vs standard surgical care. Objective: To determine the factors associated with
underestimation of invasive cancer in patients with a clinical diagnosis of non
high-grade DCIS that would preclude active surveillance. Design, Setting, and
Participants: A retrospective cohort study was conducted using records from the
National Cancer Database from January 1, 1998, to December 31, 2012, of female
patients 40 to 99 years of age with a clinical diagnosis of non-high-grade DCIS
who underwent definitive surgical treatment. Data analysis was conducted from
November 1, 2015, to February 4, 2017. Exposures: Patients with an upgraded
diagnosis of invasive carcinoma vs those with a diagnosis of DCIS based on final
surgical pathologic findings. Main Outcomes and Measures: The proportions of
cases with an upgraded diagnosis of invasive carcinoma from final surgical
pathologic findings were compared by tumor, host, and system characteristics.
Results: Of 37 544 women (mean [SD] age, 59.3 [12.4] years) presenting with a
clinical diagnosis of non-high-grade DCIS, 8320 (22.2%) had invasive carcinoma
based on final pathologic findings. Invasive carcinomas were more likely to be
smaller (>0.5 to <=1.0 cm vs <=0.5 cm: odds ratio [OR], 0.73; 95% CI, 0.67-0.79;
>1.0 to <=2.0 cm vs <=0.5 cm: OR, 0.42; 95% CI, 0.39-0.46; >2.0 to <=5.0 cm vs
<=0.5 cm: OR, 0.19; 95% CI, 0.17-0.22; and >5.0 cm vs <=0.5 cm: OR, 0.11; 95% CI,
0.08-0.15) and lower grade (intermediate vs low: OR, 0.75; 95% CI, 0.69-0.80).
Multivariate logistic regression analysis demonstrated that younger age (60-79 vs
40-49 years: OR, 0.84; 95% CI, 0.77-0.92; and >=80 vs 40 to 49 years: OR, 0.76;
95% CI, 0.64-0.91), negative estrogen receptor status (positive vs negative: OR,
0.39; 95% CI, 0.34-0.43), treatment at an academic facility (academic vs
community: OR, 2.08; 95% CI, 1.82-2.38), and higher annual income (>$63 000 vs
<$38 000: OR, 1.14; 95% CI, 1.02-1.28) were significantly associated with an
upgraded diagnosis of invasive carcinoma based on final pathologic findings.
Conclusions and Relevance: When selecting patients for active surveillance of
DCIS, factors other than tumor biology associated with invasive carcinoma based
on final pathologic findings may need to be considered. At the time of
randomization to active surveillance, a significant proportion of patients with
non-high-grade DCIS will harbor invasive carcinoma.
PMID- 28700804
TI - Characteristics of Patients Presenting to the Emergency Department and Urgent
Care for Treatment of Sunburn.
PMID- 28700806
TI - Infection After Pancreatic Surgery: Superficial and Deep Thoughts.
PMID- 28700805
TI - Efficacy of Lisdexamfetamine in Adults With Moderate to Severe Binge-Eating
Disorder: A Randomized Clinical Trial.
AB - Importance: The ability of pharmacotherapies to prevent relapse and maintain
efficacy with long-term treatment in psychiatric conditions is important.
Objective: To assess lisdexamfetamine dimesylate maintenance of efficacy in
adults with moderate to severe binge-eating disorder. Design, Setting, and
Participants: A multinational, phase 3, double-blind, placebo-controlled,
randomized withdrawal study including 418 participants was conducted at 49
clinical research study sites from January 27, 2014, to April 8, 2015. Eligible
adults met DSM-IV-R binge-eating disorder criteria and had moderate to severe
binge eating disorder (>=3 binge-eating days per week for 14 days before open
label baseline; Clinical Global Impressions-Severity [CGI-S] scores >=4 [moderate
severity] at screening and open-label baseline). Following a 12-week, open-label
phase (dose optimization, 4 weeks [lisdexamfetamine dimesylate, 50 or 70 mg];
dose maintenance, 8 weeks), lisdexamfetamine responders (<=1 binge eating day per
week for 4 consecutive weeks and CGI-S scores <=2 at week 12) were randomized to
placebo or continued lisdexamfetamine during a 26-week, double-blind, randomized
withdrawal phase. Interventions: Lisdexamfetamine administration. Main Outcomes
and Measures: The primary outcome variable, time to relapse (>=2 binge-eating
days per week for 2 consecutive weeks and >=2-point CGI-S score increases from
randomized withdrawal baseline), was analyzed using a log-rank test (primary
analysis); the analysis was stratified for dichotomized 4-week cessation status.
Safety assessments included treatment-emergent adverse events. Results: Of the
418 participants enrolled in the open-label phase of the study, 411 (358 [87.1%]
women; mean [SD] age, 38.3 [10.4] years) were included in the safety analysis
set. Of 275 randomized lisdexamfetamine responders (placebo, n = 138;
lisdexamfetamine, n = 137), the observed proportions of participants meeting
relapse criteria were 3.7% (5 of 136) for lisdexamfetamine and 32.1% (42 of 131)
for placebo. Lisdexamfetamine demonstrated superiority over placebo on the log
rank test (chi21, 40.37; P < .001) for time to relapse; the hazard ratio, based
on a Cox proportional hazards model for lisdexamfetamine vs placebo, was 0.09
(95% CI, 0.04-0.23). The treatment-emergent adverse events observed were
generally consistent with the known profile of lisdexamfetamine. Conclusions and
Relevance: Risk of binge-eating relapse over 6 months was lower in participants
continuing lisdexamfetamine than in those randomized to placebo. The hazard for
relapse was lower with lisdexamfetamine than placebo. Trial Registration:
clinicaltrials.gov Identifier: NCT02009163.
PMID- 28700807
TI - Association of Antidepressant Medication Use During Pregnancy With Intellectual
Disability in Offspring.
AB - Importance: Maternal antidepressant medication use during pregnancy has
previously been associated with adverse outcomes in offspring, but to our
knowledge, the association with intellectual disability (ID) has not been
investigated. Objectives: To examine the association of maternal antidepressant
medication use during pregnancy with ID in offspring and investigate the
importance of parental mental illness for such an association. Design, Setting,
and Participants: A population-based cohort study of 179 007 children born from
January 1, 2006, through December 31, 2007, with complete parental information
from national registers who were followed up from birth throughout 2014. Main
Outcomes and Measures: We estimated relative risks (RRs) and 95% CIs of ID in
children exposed during pregnancy to any antidepressant medication or
specifically to selective serotonin reuptake inhibitor (SSRI) antidepressants,
all other non-SSRI antidepressants, or other nonantidepressant psychotropic
medications. Analyses were adjusted for potential confounders. In addition to
full population analyses, we used a subsample to compare mothers who used
antidepressants during pregnancy with mothers who had at least one diagnosis of
depression or anxiety before childbirth but did not use antidepressants during
pregnancy. Results: Of the 179 007 children included in the study (mean [SD] age
at end of follow-up, 7.9 [0.6] years; 92 133 [51.5%] male and 86 874 [48.5%]
female), ID was diagnosed in 37 children (0.9%) exposed to antidepressants and in
819 children (0.5%) unexposed to antidepressants. With adjustment for potential
confounders, the RR of ID after antidepressant exposure was estimated at 1.33
(95% CI, 0.90-1.98) in the full population sample and 1.64 (95% CI, 0.95-2.83) in
the subsample of women with depression. Results from analyses of SSRI
antidepressants, non-SSRI antidepressants, and nonantidepressant psychotropic
medications and analyses in the clinically relevant subsample did not deviate
from the full-sample results. Conclusions and Relevance: The unadjusted RR of ID
was increased in offspring born to mothers treated with antidepressants during
pregnancy. After adjustment for confounding factors, however, the current study
did not find evidence of an association between ID and maternal antidepressant
medication use during pregnancy. Instead, the association may be attributable to
a mechanism integral to other factors, such as parental age and mother's
psychiatric disorder.
PMID- 28700808
TI - The Moderating Effect of Childhood Maltreatment on the Relations Among PTSD
Symptoms, Positive Urgency, and Negative Urgency.
AB - Childhood maltreatment increases the risk for posttraumatic stress disorder
(PTSD) and comorbid substance use disorder (SUD). One pathway by which this
occurs is through impaired emotion regulation. Past research has shown that
negative urgency, a deficit in the regulation of negative emotions, is strongly
related to PTSD in those with comorbid SUD. However, there is minimal research on
the relation between positive urgency and PTSD in those with comorbid SUD. The
current study investigated the association between childhood maltreatment,
positive urgency, negative urgency, and PTSD symptoms among those with SUD.
Results suggested that PTSD was associated with negative urgency and positive
urgency overall. Childhood maltreatment did not moderate the association between
negative urgency and PTSD. Childhood emotional abuse, emotional neglect, and
sexual abuse moderated the relation between positive urgency and PTSD (DeltaR2 =
.04 to .10). The association between PTSD and positive urgency was only
significant at lower levels of emotional abuse and neglect. Future research
should further examine the processing of positive emotions in those with PTSD and
comorbid SUD. Findings might inform clinical interventions among populations
exposed to childhood maltreatment to reduce or prevent the development of
psychopathology.
PMID- 28700809
TI - Number of ocular syphilis cases creeps to record high.
PMID- 28700810
TI - To Avoid Chasing Incorrect Chemical Structures of Chiral Compounds: Raman Optical
Activity and Vibrational Circular Dichroism Spectroscopies.
AB - A chemical structure (CS) identifies the connectivities between atoms, and the
nature of those connections, for a given elemental composition. For chiral
molecules, in addition to the identification of CS, the identification of the
correct absolute configuration (AC) is also needed. Several chiral natural
products are known whose CSs were initially misidentified and later corrected,
and these errors were often discovered during the total synthesis of natural
products. In this work, we present a new and convenient approach that can be used
with Raman optical activity (ROA) and vibrational circular dichroism (VCD)
spectroscopies, to distinguish between the correct and incorrect CSs of chiral
compounds. This approach involves analyzing the spectral similarity overlap
between experimental spectra and those predicted with advanced quantum chemical
theories. Significant labor needed for establishing the correct CSs via chemical
syntheses of chiral natural products can thus be avoided.
PMID- 28700811
TI - Probing for congenital nasolacrimal duct obstruction.
AB - BACKGROUND: Congenital nasolacrimal duct obstruction (NLDO) is a common condition
causing excessive tearing in the first year of life. Infants present with
excessive tearing or mucoid discharge from the eyes due to blockage of the
nasolacrimal duct system, which can result in maceration of the skin of the
eyelids and local infections, such as conjunctivitis, that may require
antibiotics. The incidence of nasolacrimal duct obstruction in early childhood
ranges from 5% to 20% and often resolves without surgery. Treatment options for
this condition are either conservative therapy, including observation (or
deferred probing), massage of the lacrimal sac and antibiotics, or probing the
nasolacrimal duct to open the membranous obstruction at the distal nasolacrimal
duct. Probing may be performed without anesthesia in the office setting or under
general anesthesia in the operating room. Probing may serve to resolve the
symptoms by opening the membranous obstruction; however, it may not be successful
if the obstruction is due to a bony protrusion of the inferior turbinate into the
nasolacrimal duct or when the duct is edematous (swollen) due to infection such
as dacryocystitis. Additionally, potential complications with probing include
creation of a false passage and injury to the nasolacrimal duct, canaliculi and
puncta, bleeding, laryngospasm, or aspiration. OBJECTIVES: To assess the effects
of probing for congenital nasolacrimal duct obstruction. SEARCH METHODS: We
searched the Cochrane Central Register of Controlled Trials (CENTRAL), which
contains the Cochrane Eyes and Vision Trials Register (2016, Issue 8); MEDLINE
Ovid (1946 to 30 August 2016); Embase.com (1947 to 30 August 2016); PubMed (1948
to 30 August 2016); LILACS (Latin American and Caribbean Health Sciences
Literature Database; 1982 to 30 August 2016), the metaRegister of Controlled
Trials (mRCT) (www.controlled-trials.com), last searched 14 August 2014;
ClinicalTrials.gov (www.clinicaltrials.gov), searched 30 August 2016; and the WHO
International Clinical Trials Registry Platform (ICTRP)
(www.who.int/ictrp/search/en), searched 30 August 2016. We did not use any date
or language restrictions in the electronic searches for trials. SELECTION
CRITERIA: We included randomized controlled trials (RCTs) that compared probing
(office-based or hospital-based under general anesthesia) versus no (or deferred)
probing or other interventions (observation alone, antibiotic drops only, or
antibiotic drops plus massage of the nasolacrimal duct). We did not include
studies that compared different probing techniques or probing compared with other
surgical procedures. We included studies in children aged three weeks to four
years who may have presented with tearing and conjunctivitis. DATA COLLECTION AND
ANALYSIS: Two review authors independently screened studies for inclusion and
independently extracted data and assessed risk of bias for the included studies.
We analyzed data using Review Manager software and evaluated the certainty of the
evidence using GRADE. MAIN RESULTS: We identified two RCTs and no ongoing
studies; one of the included RCTs was registered. The studies reported on 303
eyes of 242 participants who had unilateral or bilateral congenital nasolacrimal
duct obstruction. For both included studies, the interventions compared were
immediate office-based probing to remove the duct obstruction versus deferred
probing, if needed, after 6 months of observation or once the child reached a
certain age.The primary outcome of the review, treatment success at 6 months, was
reported partially in one study. Treatment success was not reported at this time
point for all children in the immediate probing group; however, 77 of 117 (66%)
eyes randomized to deferred probing had resolved without surgery 6 months after
randomization and 40 (34%) eyes did not resolve without probing. For children who
had unilateral NLDO, those randomized to immediate probing had treatment success
more often than those who were randomized to deferred probing (RR 1.41, 95% CI
1.12 to 1.78; 163 children; moderate-certainty evidence). Treatment success for
all children was assessed in the study at age 18 months; as an ad hoc analysis in
the included study, results were presented separately for children with
unilateral and bilateral NLDO (RR 1.13, 95% CI 0.99 to 1.28 and RR 0.86, 95% CI
0.70 to 1.06, respectively; very low-certainty evidence).In the other small study
(26 eyes of 22 children), more eyes that received immediate probing were cured
within one month after surgery compared with eyes that were randomized to
deferred probing and analyzed at age 15 months (RR 2.56, 95% CI 1.16 to 5.64). We
considered the evidence to be low-certainty due to imprecision from the small
study size and risk of bias concerns due to attrition bias.One study reported on
the number of children that required reoperation; however, these data were
reported only for immediate probing group. Nine percent of children with
unilateral NLDO and 13% with bilateral NLDO required secondary procedures.One
study reported cost-effectiveness of immediate probing versus deferred probing.
The mean cost of treatment for immediate probing was less than for deferred
probing; however, there is uncertainty as to whether there is a true cost
difference (mean difference USD -139, 95% CI USD -377 to 94; moderate-certainty
evidence).Reported complications of the treatment were not serious. One study
reported that there were no complications for any surgery and no serious adverse
events, while the other study reported that bleeding from the punctum occurred in
20% of all probings. AUTHORS' CONCLUSIONS: The effects and costs of immediate
versus deferred probing for NLDO are uncertain. Children who have unilateral NLDO
may have better success from immediate office probing, though few children have
participated in these trials, and investigators examined outcomes at disparate
time points. Determining whether to perform the procedure and its optimal timing
will require additional studies with greater power and larger, well-run clinical
trials to help our understanding of the comparison.
PMID- 28700812
TI - Disparities in location of death of adolescents and young adults with cancer: A
longitudinal, population study in California.
AB - BACKGROUND: Patients with a terminal illness should have access to their chosen
location of death. Cancer is the leading cause of non-accidental death among
adolescents and young adults (AYAs; those aged 15-39 years). Although surveys
have suggested that a majority of these patients prefer a home death, to the
authors' knowledge, little is known regarding their barriers to accessing their
preferred location of death. As a first step, the authors sought to determine,
across a large population, 20-year trends in the location of death among AYA
patients with cancer. METHODS: Using the Vital Statistics Death Certificate
Database of the California Office of Statewide Health Planning and Development,
the authors performed a retrospective, population-based analysis of California
patients with cancer aged 15 to 39 years who died between 1989 and 2011.
Sociodemographic and clinical factors associated with hospital death were
examined using multivariable logistic regression. RESULTS: Of 30,573 AYA oncology
decedents, 57% died in a hospital, 33% died at home, and 10% died in other
locations (eg, hospice facility or nursing facility). Between 1989 and 1994,
hospital death rates decreased from 68.3% to 53.6% and at-home death rates
increased from 16.8% to 35.5%. Between 1995 and 2011, these rates were stable.
Those individuals who were more likely to die in a hospital were those aged <30
years, of minority race, of Hispanic ethnicity, who lived <=10 miles from a
specialty center, and who had a diagnosis of leukemia or lymphoma. CONCLUSIONS:
Overall, the majority of AYA cancer deaths occurred in a hospital, with a 5-year
shift to more in-home deaths that abated after 1995. In-hospital deaths were more
common among younger patients, patients of minority race/ethnicities, and those
with a leukemia or lymphoma diagnosis. Further study is needed to determine
whether these rates and disparities are consistent with patient preferences.
Cancer 2017;123:4178-4184. (c) 2017 American Cancer Society.
PMID- 28700813
TI - Genesis of a Co-Salicylaldimine Complex on Silica Followed in Situ by FTIR and
XAS.
AB - Several strategies have been proposed to replace soluble metallorganic complexes
in organic solvents by similar molecular entities immobilized on non-reactive
solids. The characterization of these complexes at atomic and molecular level
during synthesis is demanding but essential to guide rational design. In the
present work, the formation of cobalt salicylaldimine complex on gamma
aminopropyl modified silica (SiO2 ) was monitored in ethanol on-line by Fourier
transform infrared spectroscopy (FTIR) and in situ X-ray absorption spectroscopy
(XAS) simultaneously using two independent cells. The organic ligand was
monitored by FTIR to follow the stepwise synthesis of the Co-salicylaldimine
complex. The oxidation state of Co, obtained by XANES, was found to be +2, while
different coordination environments were observed in the presence or absence of
the pendant organic ligand produced in situ on SiO2 . EXAFS analysis inferred
that the oxidation state and the local structure of the Co2+ ion on the modified
SiO2 surface was similar to that of a salen-complex with four Co-O/N bonds.
PMID- 28700814
TI - Alternative outflow reconstruction in domino liver transplantation.
PMID- 28700815
TI - Mesenchymal stem cells and their immunosuppressive role in transplantation
tolerance.
AB - Since they were first described, mesenchymal stem cells (MSCs) have been shown to
have important effector mechanisms and the potential for use in cell therapy. A
great deal of research has been focused on unveiling how MSCs contribute to anti
inflammatory responses, including describing several cell populations involved
and identifying soluble and other effector molecules. In this review, we discuss
some of the contemporary evidence for use of MSCs in the field of immune
tolerance, with a special emphasis on transplantation. Although considerable
effort has been devoted to understanding the biological function of MSCs,
additional resources are required to clarify the mechanisms of their induction of
immune tolerance, which will undoubtedly lead to improved clinical outcomes for
MSC-based therapies.
PMID- 28700817
TI - An Esterase-Sensitive Prodrug Approach for Controllable Delivery of Persulfide
Species.
AB - A strategy to deliver a well-defined persulfide species in a biological medium is
described. Under near physiological conditions, the persulfide prodrug can be
activated by an esterase to generate a "hydroxymethyl persulfide" intermediate,
which rapidly collapses to form a defined persulfide. Such persulfide prodrugs
can be used either as chemical tools to study persulfide chemistry and biology or
for future development as H2 S-based therapeutic reagents. Using the persulfide
prodrugs developed in this study, the reactivity between S-methyl
methanethiosulfonate (MMTS) with persulfide was unambiguously demonstrated.
Furthermore, a representative prodrug exhibited potent cardioprotective effects
in a murine model of myocardial ischemia-reperfusion (MI/R) injury with a bell
shape therapeutic profile.
PMID- 28700816
TI - Comparative "nocebo effects" in older patients enrolled in cancer therapeutic
trials: Observations from a 446-patient cohort.
AB - BACKGROUND: A nocebo is an inert substance associated with adverse events.
Although previous studies have examined the positive (placebo) effects of such
inert substances, few have examined negative (nocebo) adverse event profiles,
particularly in older patients who have higher morbidity and can experience
frequent and severe adverse events from cancer therapy. METHODS: This study
focused on placebo/nocebo-exposed patients who participated in 2 double-blind,
placebo-controlled, cancer therapeutic studies, namely, North Central Cancer
Therapy Group trial NCCTG 97-24-51 and American College of Surgeons Oncology
Group trial Z9001, with the goal of reporting the comparative, age-based adverse
event rates, as reported during the conduct of these trials. RESULTS: Among the
446 patients who received only placebo/nocebo and who were the focus of the
current report, 161 were aged >=65 years at the time of respective trial entry,
and 5234 adverse events occurred. Unadjusted adverse event rates did not differ
significantly between patients aged >=65 years and younger patients (rate ratio,
1.01; 99% confidence interval, 0.47-2.02), and the findings were similar findings
for grade 2 or worse adverse events and for all symptom-driven adverse events
(for example, pain, loss of appetite, anxiety). Adjustment for sex, ethnicity,
baseline performance score, and individual trial resulted in no significant age
based differences in adverse event rates. Similar findings were observed with an
age threshold of 70 years. CONCLUSIONS: Adverse events are equally common in
older and younger cancer patients who are exposed to nocebo and thus require the
same degree of clinical consideration regardless of age. Cancer 2017;123:4193
4198. (c) 2017 American Cancer Society.
PMID- 28700818
TI - Fetal middle cerebral artery Doppler to time intrauterine transfusion in red-cell
alloimmunization: a randomized trial.
AB - OBJECTIVES: To evaluate whether Doppler measurement of middle cerebral artery
peak systolic velocity (MCA-PSV) for timing subsequent intrauterine transfusions
(IUTs) in fetuses that had undergone one IUT for anemia secondary to red-cell
alloimmunization is non-inferior to timing based on expected decrease in fetal
hematocrit (Hct) or fetal hemoglobin level, without compromising infant
hemoglobin at birth. METHODS: This was an international, pragmatic multicenter
randomized controlled trial. Women with a pregnancy complicated by fetal anemia
secondary to red-cell alloimmunization (due to any antibody alone or in
combination), as indicated by the need to undergo a single IUT, were eligible for
inclusion. Women were randomized to the determination of timing of further
transfusion(s) by Doppler measurement of MCA-PSV (MCA-PSV Group), with a serial
upward trend of values >1.5 multiples of the median considered indicative of the
need for another IUT, or timing of transfusion by a decrease in fetal Hct (fetal
Hct Group), with subsequent IUTs timed according to an estimated fall in fetal
Hct of 1% per day or fetal hemoglobin of 0.3 g/dL per day, to maintain fetal
hemoglobin level between 7 and 10 g/dL. The primary outcome was infant hemoglobin
level measured at birth. RESULTS: A total of 71 women were randomized, 36 to the
MCA-PSV Group and 35 to the fetal Hct Group. Median gestational age at
randomization was 30.3 weeks, the majority of women were Caucasian and non
smokers, 9.9% of women had Kell alloimmunization, and 14% of fetuses were
hydropic at their first IUT. No statistically significant differences between the
two treatment groups were observed with regard to mean hemoglobin levels at birth
(MCA-PSV Group, 10.36 +/- 3.82 g/dL vs fetal Hct Group, 12.03 +/- 3.14 g/dL;
adjusted mean difference -1.56 g/dL (95% CI, -3.24 to 0.13 g/dL); P = 0.070), or
the number of IUTs performed after randomization (MCA-PSV Group, 1.75 +/- 1.79 vs
fetal Hct Group 1.80 +/- 1.32; adjusted relative risk 0.88 (95% CI, 0.61-1.26); P
= 0.474). There was no statistically significant difference between the two
groups with respect to the risk of adverse infant outcomes related to
alloimmunization or procedure-related complications. CONCLUSION: Both Doppler
measurement of MCA-PSV and estimation of the decrease in fetal Hct or hemoglobin
can be used to determine the timing of second and subsequent IUTs in fetuses with
red-cell alloimmunization. Copyright (c) 2017 ISUOG. Published by John Wiley &
Sons Ltd.
PMID- 28700819
TI - Posterior dopamine D2/3 receptors and brain network functional connectivity.
AB - Recent studies suggest that dopaminergic tone influences resting state activity
in multiple brain networks. Although dopamine receptors and transporters have
been identified in the posteromedial and parietal cortices, which are linked to
functional networks such as the default mode network (DMN), the relationship
between dopamine receptor distribution in these posterior regions and resting
state connectivity has yet to be explored. Here, we used a multi-modal
neuroimaging strategy, combining resting-state functional magnetic resonance
imaging (rsfMRI) and [18 F]-fallypride high-resolution positron emission
tomography (PET), to examine the association between within-network functional
connectivity and the dopamine D2/3 receptor distribution in the posterior portion
of the brain in 13 healthy adults. Our results indicate that the posterior
distribution of D2/3 receptors coincides primarily with the posterior portion of
the DMN. Furthermore, in the posterior portion of the brain, the level of [18 F]
fallypride binding in the posteromedial cortex correlated positively with the
functional connectivity strength of the DMN and sensorimotor network, and
negatively with the functional connectivity strength of the dorsal attention
network, the salience network, and a network that included the anterior part of
the temporo-parietal junction. On the basis of these findings, we propose that
posterior brain dopamine influences the configuration of the posterior DMN and
several other functional brain networks. The posterior distribution of D2/3
receptors binding (hot colour spectrum) coincides with the functional
connectivity of the posterior portion of the default mode network (green colour
spectrum). The mean BPND in a posteromedial cortex and the mean ICA-Z score in
the precuneus showed significant positive correlation.
PMID- 28700820
TI - Diastereo- and Enantioselective Synthesis of beta-Aminoboronate Esters by
Copper(I)-Catalyzed 1,2-Addition of 1,1-Bis[(pinacolato)boryl]alkanes to Imines.
AB - Reported herein is an efficient copper(I)-catalytic system for the diastereo- and
enantioselective 1,2-addition of 1,1-bis[(pinacolato)boryl]alkanes to protected
imines to afford synthetically valuable enantioenriched beta-aminoboron compounds
bearing contiguous stereogenic centers. The reaction exhibits a broad scope with
respect to protected imines and 1,1-bis[(pinacolato)boryl]alkanes, thus providing
beta-aminoboronate esters with excellent diastereo- and enantioselectivity. The
synthetic utility of the obtained beta-aminoboronate ester was also demonstrated.
PMID- 28700822
TI - Laser Desorption Postionization Mass Spectrometry Imaging of Folic Acid Molecules
in Tumor Tissue.
AB - Mass spectrometry imaging (MSI) is an innovative and powerful tool in biomedical
research. It is well-known that folic acid (FA) has a high affinity for folic
acid receptor (FR), which is overexpressing in epithelial cancer. Herein, we
propose a novel method to diagnose cancer through direct mapping of the label
free FA spatial distribution in tissue sections by state-of-the-art laser
desorption postionization-mass spectrometry imaging (LDPI-MSI). Compared with
other tumor imaging methods, such as fluorescence imaging, photoacoustic imaging
(PAI), magnetic resonance imaging (MRI), and micro-SPECT/CT, complicated
synthesis and labeling processes are not required. The LDPI-MSI was performed on
30 MUm thick sections from a murine model of breast cancer (inoculation of 4T1
cells) that were predosed with 20 mg/kg of FA. The image obtained from the
characteristic mass spectrometric signature of FA at m/z 265 illustrated that FA
was concentrated primarily in tumor tissue and displayed somewhat lower retention
in adjacent normal controls. The results suggest that the proposed method could
be used potentially in cancer diagnosis.
PMID- 28700821
TI - Gene expression profiling of prostate tissue identifies chromatin regulation as a
potential link between obesity and lethal prostate cancer.
AB - BACKGROUND: Obese men are at higher risk of advanced prostate cancer and cancer
specific mortality; however, the biology underlying this association remains
unclear. This study examined gene expression profiles of prostate tissue to
identify biological processes differentially expressed by obesity status and
lethal prostate cancer. METHODS: Gene expression profiling was performed on tumor
(n = 402) and adjacent normal (n = 200) prostate tissue from participants in 2
prospective cohorts who had been diagnosed with prostate cancer from 1982 to
2005. Body mass index (BMI) was calculated from the questionnaire immediately
preceding cancer diagnosis. Men were followed for metastases or prostate cancer
specific death (lethal disease) through 2011. Gene Ontology biological processes
differentially expressed by BMI were identified using gene set enrichment
analysis. Pathway scores were computed by averaging the signal intensities of
member genes. Odds ratios (ORs) for lethal prostate cancer were estimated with
logistic regression. RESULTS: Among 402 men, 48% were healthy weight, 31% were
overweight, and 21% were very overweight/obese. Fifteen gene sets were enriched
in tumor tissue, but not normal tissue, of very overweight/obese men versus
healthy-weight men; 5 of these were related to chromatin modification and
remodeling (false-discovery rate < 0.25). Patients with high tumor expression of
chromatin-related genes had worse clinical characteristics (Gleason grade > 7,
41% vs 17%; P = 2 * 10-4 ) and an increased risk of lethal disease that was
independent of grade and stage (OR, 5.26; 95% confidence interval, 2.37-12.25).
CONCLUSIONS: This study improves our understanding of the biology of aggressive
prostate cancer and identifies a potential mechanistic link between obesity and
prostate cancer death that warrants further study. Cancer 2017;123:4130-4138. (c)
2017 American Cancer Society.
PMID- 28700823
TI - Complex Three-Dimensional Magnetic Ordering in Segmented Nanowire Arrays.
AB - A comprehensive three-dimensional picture of magnetic ordering in high-density
arrays of segmented FeGa/Cu nanowires is experimentally realized through the
application of polarized small-angle neutron scattering. The competing energetics
of dipolar interactions, shape anisotropy, and Zeeman energy in concert stabilize
a highly tunable spin structure that depends heavily on the applied field and
sample geometry. Consequently, we observe ferromagnetic and antiferromagnetic
interactions both among wires and between segments within individual wires. The
resulting magnetic structure for our nanowire sample in a low field is a fan with
magnetization perpendicular to the wire axis that aligns nearly antiparallel from
one segment to the next along the wire axis. Additionally, while the low-field
interwire coupling is ferromagnetic, application of a field tips the moments
toward the nanowire axis, resulting in highly frustrated antiferromagnetic stripe
patterns in the hexagonal nanowire lattice. Theoretical calculations confirm
these observations, providing insight into the competing interactions and
resulting stability windows for a variety of ordered magnetic structures. These
results provide a roadmap for designing high-density magnetic nanowire arrays for
spintronic device applications.
PMID- 28700824
TI - Application of Hydrogen/Deuterium Exchange-Mass Spectrometry to Biopharmaceutical
Development Requirements: Improved Sensitivity to Detection of Conformational
Changes.
AB - The usefulness of the higher-order structure information provided by
hydrogen/deuterium exchange mass spectrometry (HDX-MS) in the protein therapeutic
field is undisputed; however, its applicability as a method for critical quality
and comparability assessment has until now not been demonstrated. Here we present
results demonstrating for the first time the applicability of the HDX-MS
technique to monitor structural changes due to methionine oxidation at
sensitivity levels realistic to the requirements of biopharmaceutical research
and development. For the analyzed heavy chain marker peptides deuterium uptake
differences due to oxidation at the conserved methionine in position 254 were
significantly verifiable at the lowest increase (1%) through spiked oxidized
IgG1.
PMID- 28700825
TI - Chemical Visualization of Sweat Pores in Fingerprints Using GO-Enhanced TOF-SIMS.
AB - Time-of-flight secondary ion mass spectrometry (TOF-SIMS) has been used in
imaging of small molecules (<500 Da) in fingerprints, such as gunshot residues
and illicit drugs. However, identifying and mapping relatively high mass
molecules are quite difficult owing to insufficient ion yield of their molecular
ions. In this report, graphene oxide (GO)-enhanced TOF-SIMS was used to detect
and image relatively high mass molecules such as poison, alkaloids (>600 Da) and
controlled drugs, and antibiotics (>700 Da) in fingerprints. Detail features of
fingerprints such as the number and distribution of sweat pores in a ridge and
even the delicate morphology of one pore were clearly revealed in SIMS images of
relatively high mass molecules. The detail features combining with identified
chemical composition were sufficient to establish a human identity and link the
suspect to a crime scene. The wide detectable mass range and high spatial
resolution make GO-enhanced TOF-SIMS a promising tool in accurate and fast
analysis of fingerprints, especially in fragmental fingerprint analysis.
PMID- 28700826
TI - Application of Coal in Electrochemical Sensing.
AB - In this work, we first report a new application of coal as a novel modified
electrode material in electrochemical sensing, achieving excellent
electrochemical performance similar to graphene and making the utilization of
coal become more multipurpose and more meaningful. Raw coal was first ball
milled, then centrifugated, and finally annealed, thus obtaining annealed coal
that possesses lots of edge-plane-like defective sites, resulting in good
electron-transfer efficiency and excellent electrocatalytic activity, which makes
it promising when used as signal amplifier material and as a modified matrix in
electrochemical sensing. And we also described an investigation into the
electrochemical and spectroscopic properties of annealed coal samples and their
application for the detection of electroactive redox molecules (rutin). Compared
with other published carbon materials modified sensors, the annealed
coal/chitosan/GCE sensor exhibited excellent electrocatalytic activity for the
determination of rutin with good sensitivity, providing a wide linear detection
range from 0.001 to 10 MUmol dm-3 and a low detection limit of 0.2 nmol dm-3 (S/N
= 3). Moreover, when the annealed coal/GCE sensor was applied for the
determination of ascorbic acid, dopamine, uric acid, guanine, and adenine
commonly contained in blood samples and urine samples, it also exhibited
excellent detection performance with strong electrocatalytic activity. This
research has opened up the application of coal in electroanalytical chemistry and
held great promise for the sensing and biosensing application, which can be
promising used as an alternative material of graphene.
PMID- 28700827
TI - Compatible Rhizosphere-Competent Microbial Consortium Adds Value to the
Nutritional Quality in Edible Parts of Chickpea.
AB - Chickpea is used as a high-energy and protein source in diets of humans and
livestock. Moreover, chickpea straw can be used as alternative of forage in
ruminant diets. The present study evaluates the effect of beneficial microbial
inoculation on enhancing the nutritional values in edible parts of chickpea. Two
rhizosphere-competent compatible microbes (Pseudomonas fluorescens OKC and
Trichoderma asperellum T42) were selected and applied to seeds either
individually or in consortium before sowing. Chickpea seeds treated with the
microbes showed enhanced plant growth [88.93% shoot length at 60 days after
sowing (DAS)] and biomass accumulation (21.37% at 120 DAS). Notably, the uptake
of mineral nutrients, viz., N (90.27, 91.45, and 142.64%), P (14.13, 58.73, and
56.84%), K (20.5, 9.23, and 35.98%), Na (91.98, 101.66, and 36.46%), Ca (16.61,
29.46, and 16%), and organic carbon (28.54, 17.09, and 18.54%), was found in the
seed, foliage, and pericarp of the chickpea plants, respectively. Additionally,
nutritional quality, viz., total phenolic (59.7, 2.8, and 17.25%), protein (9.78,
18.53, and 7.68%), carbohydrate content (26.22, 30.21, and 26.63%), total
flavonoid content (3.11, 9.15, and 7.81%), and reducing power (112.98, 75.42, and
111.75%), was also found in the seed, foliage, and pericarp of the chickpea
plants. Most importantly, the microbial-consortium-treated plants showed the
maximum increase of nutrient accumulation and enhancement in nutritional quality
in all edible parts of chickpea. Nutritional partitioning in different edible
parts of chickpea was also evident in the microbial treatments compared to their
uninoculated ones. The results thus clearly demonstrated microbe-mediated
enhancement in the dietary value of the edible parts of chickpea because seeds
are consumed by humans, whereas pericarp and foliage (straw) are used as an
alternative of forage and roughage in ruminant diets.
PMID- 28700828
TI - Herbicidal Spectrum, Absorption and Transportation, and Physiological Effect on
Bidens pilosa of the Natural Alkaloid Berberine.
AB - Berberine is a natural herbicidal alkaloid from Coptis chinensis Franch. Here we
characterized its herbicidal spectrum and absorption and transportation in the
plant, along with the possible mechanism. Berberine showed no effect on the
germination of the 10 tested plants. The IC50 values of berberine on the primary
root length and fresh weight of the 10 tested plants ranged from 2.91 to 9.79 mg
L-1 and 5.76 to 35.07 mg L-1, respectively. Berberine showed a similar herbicidal
effect on Bidens pilosa as the commercial naturally derived herbicide
cinmethylin. HPLC and fluorescence analysis revealed that berberine was mainly
absorbed by B. pilosa root and transported through vascular bundle acropetally.
Enzyme activity studies, GC-MS analysis, and SEM and TEM observations indicated
that berberine might first function on the cell membrane indicated by variation
of the IUFA percent and then cause POD, PPO, and SOD activity changes and
cellular structure deformity, which was eventually expressed as the decrease of
cell adaptation ability and abnormal cell function and may even result in cell
death. Environmental safety evaluation tests revealed that berberine was low in
toxicity to Brachydanio rerio. These indicate that berberine has the potential to
be a bioherbicide and/or a lead molecule for new herbicides.
PMID- 28700829
TI - Fast, Sensitive, and Quantitative Point-of-Care Platform for the Assessment of
Drugs of Abuse in Urine, Serum, and Whole Blood.
AB - Drug abuse is a major public health problem in many countries in Europe and North
America. Currently available platforms for drug abuse assessment are facing
technical challenges of nonquantitation, inaccuracy, low throughput,
incompatibility with diverse complex specimens, long assay times, and requirement
of instrument and/or expertise for readout. Here, we report an integrated
competitive volumetric-bar-chart chip (CV-Chip) to assay multiple drug targets at
the point-of-care (POC). To the best of our knowledge, it is the first time that
a POC platform has been demonstrated to fully address the above-mentioned
limitations. We applied this integrated CV-chip platform to assay multiple drugs
in 38 patient urine and serum samples and validated the on-chip results with an
LC-MS/MS method, indicating a clinical sensitivity and specificity of 0.94 and
1.00, respectively. We further demonstrated that the combination of an on-chip
blood separator with the CV-Chip enabled the platform to directly assay finger
prick whole blood samples, which have always been recognized as an ideal
biospecimen for POC detections. In summary, this integrated CV-Chip is able to
serve as a sensitive, accurate, fast, portable, readout visible, and minimally
invasive platform for drug abuse assessment.
PMID- 28700830
TI - Spectral and Photophysical Behavior of Cytisine in n-Hexane. Experimental
Evidence for the S1(n,pi*) -> S0 Fluorescence.
AB - Spectral and photophysical properties of (-)-cytisine (the compound used as a
smoking cessation aid and a potential drug in Alzheimer's and Parkinson's
diseases) were investigated. The two conformers of cytisine, whose presence in
the S0 state has been earlier proved by the NMR and IR methods as well as in
theoretical calculation, in nonpolar n-hexane show a rarely observed prompt
fluorescence from the S1(n,pi*) excited state. This observation is unambiguously
evidenced by very small radiative rate constants of these two emitting
conformers, kF = 7.4 * 105 and 3.0 * 105 s-1. Their lifetimes in the S1(n,pi*)
state are relatively long, tauS1 = 1.9 and 6.7 ns; therefore, their fluorescence
quantum yield is relatively high phiF ~ 10-3. The long-wavelength band in the
cytisine absorption originates from the excitation to the S2(pi,pi*) state, while
the S1(n,pi*) state is not observed in this spectrum. Thus, the excited state
S2(pi,pi*) is manifested only in the absorption spectrum, while the excited state
S1(n,pi*) is seen only in the fluorescence spectrum, so cytisine in n-hexane is
characterized by close lying (n,pi*) and (pi,pi*) excited singlet states.
PMID- 28700831
TI - Robust Molecular Anchoring to Graphene Electrodes.
AB - Recent advances in the engineering of picoscale gaps between electroburnt
graphene electrodes provide new opportunities for studying electron transport
through electrostatically gated single molecules. But first we need to understand
and develop strategies for anchoring single molecules to such electrodes. Here,
for the first time we present a systematic theoretical study of transport
properties using four different modes of anchoring zinc-porphyrin monomer, dimer,
and trimer molecular wires to graphene electrodes. These involve either amine
anchor groups, covalent C-C bonds to the edges of the graphene, or coupling via
pi-pi stacking of planar polyaromatic hydrocarbons formed from pyrene or
tetrabenzofluorene (TBF). pi-pi stacked pyrene anchors are particularly stable,
which may be advantageous for forming robust single-molecule transistors. Despite
their planar, multiatom coupling to the electrodes, pyrene anchors can exhibit
both destructive interference and different degrees of constructive interference,
depending on their connectivity to the porphyrin wire, which makes them
attractive also for thermoelectricity. TBF anchors are more weakly coupled to
both the graphene and the porphyrin wires and induce negative differential
conductance at finite source-drain voltages. Furthermore, although direct C-C
covalent bonding to the edges of graphene electrodes yields the highest
electrical conductance, electron transport is significantly affected by the shape
and size of the graphene electrodes because the local density of states at the
carbon atoms connecting the electrode edges to the molecule is sensitive to the
electrode surface shape. This sensitivity suggests that direct C-C bonding may be
the most desirable for sensing applications. The ordering of the low-bias
electrical conductances with different anchors is as follows: direct C-C coupling
> pi-pi stacking with the pyrene anchors > direct coupling via amine anchors > pi
pi stacking with TBF anchors. Despite this dependency of conductances on the mode
of anchoring, the decay of conductance with the length of the zinc-porphyrin
wires is relatively insensitive with the associated attenuation factor beta lying
between 0.9 and 0.11 A-1.
PMID- 28700832
TI - A 12-week low-carbohydrate, high-fat diet improves metabolic health outcomes over
a control diet in a randomised controlled trial with overweight defence force
personnel.
AB - Overweight, obesity, and poor health is becoming a global concern for defence
force personnel. Conventional nutrition guidelines are being questioned for their
efficacy in achieving optimal body composition and long-term health. This study
compared the effects of a 12-week low-carbohydrate, high-fat diet with a
conventional, high-carbohydrate, low-fat diet on weight reduction and metabolic
health outcomes in at-risk New Zealand Defence Force personnel. In this
randomised controlled trial, 41 overweight personnel were assigned to
intervention and control groups. Weight, waist circumference, fasting lipids, and
glycaemic control were assessed at baseline and at 12 weeks. Within-group change
scores were analysed using the t statistic and interpreted using a p < 0.05 level
of statistical significance. Between-group mean differences and confidence
intervals were analysed using effect sizes and magnitude-based inferences. Twenty
six participants completed the trial (14 intervention, 12 control). Both groups
showed statistically significant weight and waist circumference reductions; the
intervention group significantly reduced triglycerides and serum glucose and
significantly increased high-density lipoprotein cholesterol (HDLc). Relative to
control, the intervention group showed small, possibly to likely beneficial
effects for weight, triglycerides, glucose, insulin, and homeostasis model
assessment of insulin resistance; moderate, likely beneficial effects for HDL
cholesterol, triglyceride:HDLc ratio and HbA1c; and a small, likely harmful
effect for low-density lipoprotein cholesterol. This dietary approach shows
promise for short-term weight loss and improved metabolic health outcomes
conditions compared with mainstream recommendations. It should be offered to
defence force personnel at least as a viable alternative means to manage their
weight and health.
PMID- 28700833
TI - Diversity and arsenic-tolerance potential of bacterial communities from soil and
sediments along a gold tailing contamination gradient.
AB - Gold tailings often release arsenic (As) contaminants into the surrounding
environment. Microorganisms play an important role in the As cycle, whereas the
effects of As on bacterial communities remain unclear. To reveal the effects of
As on the diversity of bacterial communities and their As-tolerance potential,
farmland soil and river sediment samples were collected at various distances from
tailings in the Dandong area of northeastern China. The bacterial communities
were analyzed using high-throughput sequencing of 16S rRNA genes. The membrane
transport proteins ArsB and (or) ACR3 pump As(III) out of the cell to resist As
toxicity. We studied the abundance and phylogeny of ArsB and ACR3 using PCR-based
clone libraries and quantitative PCR. The bacterial community was divided into 10
phyla and 59 genera. The transformation from As(V) to As(III) was predominant,
which was coupled with denitrification. Both ArsB and ACR3 likely evolved from
different orders of Proteobacteria. The arsB gene seems to be more stable in
bestowing bacteria with the capability to respond to the As concentration.
Moreover, As with iron, manganese, and total organic carbon also influenced the
clustering relationships of samples and bacterial distribution.
PMID- 28700834
TI - Petroleum ether extract of Njavara rice (Oryza sativa) bran upregulates the JAK2
STAT3-mediated anti-inflammatory profile in macrophages and aortic endothelial
cells promoting regression of atherosclerosis.
AB - "Njavara" (Oryza sativa L.) is a unique rice variety grown in Kerala that is
reported to have significantly higher antioxidant, anti-inflammatory, chemical
indices, and bioactive components compared with staple rice varieties. However,
the role of NBE in reversing the atherosclerosis development remains unclear. The
present study aimed to elucidate the role of NBE in promoting atherosclerotic
regression. Male New Zealand white breed rabbits were divided into three groups.
Group I was the control, group II was the regression control, and group III was
NBE treated (100 mg/kg body mass). Serum and tissue lipids, CRP, antioxidant
enzyme activities, mRNA, and protein expression of genes of RTC and mRNA
expression of cytokines were studied. The current study showed that
hypercholesterolemic rabbits treated with NBE decreased the serum and tissue
lipids concentrations, ApoB expression, and CRP levels and enhanced the
activities of antioxidant enzymes and PON1expression, JAK2, STAT3, ABCA1, and
ApoA. Our results indicate that NBE attenuates proinflammatory cytokine
production (IL-1beta), enhanced expression and interactions of ABCA1/ApoA1
leading to JAK2/STAT3 activation in macrophages switching to an anti-inflammatory
milieu in the system, and enhanced expression of IL-10 and decreased expression
of ApoB, indicating that treatment with NBE facilitates plaque regression.
PMID- 28700835
TI - Frequency of Evidence-Based Screening for Diabetic Retinopathy.
PMID- 28700836
TI - Frequency of Evidence-Based Screening for Diabetic Retinopathy.
PMID- 28700838
TI - The Chair Grant.
PMID- 28700839
TI - Amyotrophic Lateral Sclerosis.
PMID- 28700840
TI - Surgical or Transcatheter Aortic-Valve Replacement.
PMID- 28700841
TI - Surgical or Transcatheter Aortic-Valve Replacement.
PMID- 28700842
TI - Surgical or Transcatheter Aortic-Valve Replacement.
PMID- 28700844
TI - Follow-up of Prostatectomy versus Observation for Early Prostate Cancer.
AB - BACKGROUND: We previously found no significant differences in mortality between
men who underwent surgery for localized prostate cancer and those who were
treated with observation only. Uncertainty persists regarding nonfatal health
outcomes and long-term mortality. METHODS: From November 1994 through January
2002, we randomly assigned 731 men with localized prostate cancer to radical
prostatectomy or observation. We extended follow-up through August 2014 for our
primary outcome, all-cause mortality, and the main secondary outcome, prostate
cancer mortality. We describe disease progression, treatments received, and
patient-reported outcomes through January 2010 (original follow-up). RESULTS:
During 19.5 years of follow-up (median, 12.7 years), death occurred in 223 of 364
men (61.3%) assigned to surgery and in 245 of 367 (66.8%) assigned to observation
(absolute difference in risk, 5.5 percentage points; 95% confidence interval
[CI], -1.5 to 12.4; hazard ratio, 0.84; 95% CI, 0.70 to 1.01; P=0.06). Death
attributed to prostate cancer or treatment occurred in 27 men (7.4%) assigned to
surgery and in 42 men (11.4%) assigned to observation (absolute difference in
risk, 4.0 percentage points; 95% CI, -0.2 to 8.3; hazard ratio, 0.63; 95% CI,
0.39 to 1.02; P=0.06). Surgery may have been associated with lower all-cause
mortality than observation among men with intermediate-risk disease (absolute
difference, 14.5 percentage points; 95% CI, 2.8 to 25.6) but not among those with
low-risk disease (absolute difference, 0.7 percentage points; 95% CI, -10.5 to
11.8) or high-risk disease (absolute difference, 2.3 percentage points; 95% CI,
11.5 to 16.1) (P=0.08 for interaction). Treatment for disease progression was
less frequent with surgery than with observation (absolute difference, 26.2
percentage points; 95% CI, 19.0 to 32.9); treatment was primarily for
asymptomatic, local, or biochemical (prostate-specific antigen) progression.
Urinary incontinence and erectile and sexual dysfunction were each greater with
surgery than with observation through 10 years. Disease-related or treatment
related limitations in activities of daily living were greater with surgery than
with observation through 2 years. CONCLUSIONS: After nearly 20 years of follow-up
among men with localized prostate cancer, surgery was not associated with
significantly lower all-cause or prostate-cancer mortality than observation.
Surgery was associated with a higher frequency of adverse events than observation
but a lower frequency of treatment for disease progression, mostly for
asymptomatic, local, or biochemical progression. (Funded by the Department of
Veterans Affairs and others; PIVOT ClinicalTrials.gov number, NCT00007644 .).
PMID- 28700843
TI - Autochthonous Crimean-Congo Hemorrhagic Fever in Spain.
AB - Crimean-Congo hemorrhagic fever (CCHF) is a widely distributed, viral, tickborne
disease. In Europe, cases have been reported only in the southeastern part of the
continent. We report two autochthonous cases in Spain. The index patient acquired
the disease through a tick bite in the province of Avila - 300 km away from the
province of Caceres, where viral RNA from ticks was amplified in 2010. The second
patient was a nurse who became infected while caring for the index patient. Both
were infected with the African 3 lineage of this virus. (Funded by Red de
Investigacion Cooperativa en Enfermedades Tropicales [RICET] and Efficient
Response to Highly Dangerous and Emerging Pathogens at EU [European Union] Level
[EMERGE].).
PMID- 28700846
TI - Crimean-Congo Hemorrhagic Fever in Spain - New Arrival or Silent Resident?
PMID- 28700845
TI - Association of Changes in Diet Quality with Total and Cause-Specific Mortality.
AB - BACKGROUND: Few studies have evaluated the relationship between changes in diet
quality over time and the risk of death. METHODS: We used Cox proportional
hazards models to calculate adjusted hazard ratios for total and cause-specific
mortality among 47,994 women in the Nurses' Health Study and 25,745 men in the
Health Professionals Follow-up Study from 1998 through 2010. Changes in diet
quality over the preceding 12 years (1986-1998) were assessed with the use of the
Alternate Healthy Eating Index-2010 score, the Alternate Mediterranean Diet
score, and the Dietary Approaches to Stop Hypertension (DASH) diet score.
RESULTS: The pooled hazard ratios for all-cause mortality among participants who
had the greatest improvement in diet quality (13 to 33% improvement), as compared
with those who had a relatively stable diet quality (0 to 3% improvement), in the
12-year period were the following: 0.91 (95% confidence interval [CI], 0.85 to
0.97) according to changes in the Alternate Healthy Eating Index score, 0.84 (95
CI%, 0.78 to 0.91) according to changes in the Alternate Mediterranean Diet
score, and 0.89 (95% CI, 0.84 to 0.95) according to changes in the DASH score. A
20-percentile increase in diet scores (indicating an improved quality of diet)
was significantly associated with a reduction in total mortality of 8 to 17% with
the use of the three diet indexes and a 7 to 15% reduction in the risk of death
from cardiovascular disease with the use of the Alternate Healthy Eating Index
and Alternate Mediterranean Diet. Among participants who maintained a high
quality diet over a 12-year period, the risk of death from any cause was
significantly lower - by 14% (95% CI, 8 to 19) when assessed with the Alternate
Healthy Eating Index score, 11% (95% CI, 5 to 18) when assessed with the
Alternate Mediterranean Diet score, and 9% (95% CI, 2 to 15) when assessed with
the DASH score - than the risk among participants with consistently low diet
scores over time. CONCLUSIONS: Improved diet quality over 12 years was
consistently associated with a decreased risk of death. (Funded by the National
Institutes of Health.).
PMID- 28700847
TI - Surgical Residents' Work Hours and Well-Being in Year 2 of the FIRST Trial.
PMID- 28700848
TI - The Economics of Indication-Based Drug Pricing.
PMID- 28700849
TI - Case 21-2017. A 28-Year-Old Pregnant Woman with Endocervical Carcinoma.
PMID- 28700850
TI - Diagnosis and Differential Diagnosis of Cushing's Syndrome.
PMID- 28700851
TI - Salt-and-Pepper Skin Changes.
PMID- 28700852
TI - Mobile Aortic Thrombi.
PMID- 28700892
TI - Healthy eating and active living after gestational diabetes mellitus (HEALD-GDM):
Rationale, design, and proposed evaluation of a randomized controlled trial.
AB - BACKGROUND: Gestational diabetes mellitus (GDM) is a common complication in
pregnancy and a significant risk factor for type 2 diabetes (T2D). Most women who
have had GDM are not engaging in health behaviours known to reduce their risk for
developing future T2D. The objective of this study is to evaluate the
effectiveness of a lifestyle modification program targeting healthy eating and
active living behaviours after a GDM pregnancy. METHOD: This trial will randomize
100 women to either a lifestyle modification program or a control condition.
Those allocated to the Healthy Eating and Active Living for Diabetes and
Gestational Diabetes Mellitus (HEALD-GDM), program will receive a previously
developed and tested 24-week program led by an Exercise Specialist at a local
recreational facility. The original HEALD program will be tailored for women with
GDM through the provision of complementary childcare at HEALD-GDM sessions and
theory-guided peer-led telephone support. Our primary outcome is the 6-month
change in objectively derived average daily moderate and vigorous physical
activity. DISCUSSION: Programs to increase physical activity in women with GDM
should carefully consider and find ways to address known barriers specific to
this population. We believe that our modified program may be successfully
translated to women who have had GDM. CLINICAL TRIALS REGISTRATION: NCT02483949.
PMID- 28700893
TI - Coronary microvascular disease as an early culprit in the pathophysiology of
diabetes and metabolic syndrome.
AB - Metabolic syndrome (MetS) is a group of cardio-metabolic risk factors that
includes obesity, insulin resistance, hypertension, and dyslipidemia; these are
also a combination of independent coronary artery disease (CAD) risk factors.
Alarmingly, the prevalence of MetS risk factors are increasing and a leading
cause for mortality. In the vasculature, complications from MetS and type 2
diabetes (T2D) can be divided into microvascular (retinopathy and nephropathy)
and macrovascular (cardiovascular diseases and erectile dysfunction). In addition
to vascular and endothelial dysfunction, vascular remodeling and stiffness are
also hallmarks of cardiovascular disease (CVD), and well-characterized vascular
changes that are observed in the early stages of hypertension, T2D, and obesity
[1-3]. In the heart, the link between obstructive atherosclerosis of coronary
macrovessels and myocardial ischemia (MI) is well established. However, recent
studies show that abnormalities in the coronary microcirculation are associated
with functional and structural changes in coronary microvessels (classically
defined as being <=150-200MUm internal diameter), which may cause or contribute
to MI even in the absence of obstractive CAD. This suggests a prognostic value of
an abnormal coronary microcirculation as an early sub-clinical culprit in the
pathogenesis and progression of heart disease in T2D and MetS. The aim of this
review is to summarize recent studies investigating the coronary microvascular
remodeling in an early pre-atherosclerotic phase of MetS and T2D, and to explore
potential mechanisms associated with the timing of coronary microvascular
remodeling relative to that of the macrovasculature.
PMID- 28700894
TI - Preparation of an Au-Pt alloy free from artifacts in magnetic resonance imaging.
AB - PURPOSE: When magnetic resonance imaging (MRI) is performed on patients carrying
metallic implants, artifacts can disturb the images around the implants, often
making it difficult to interpret them appropriately. However, metallic materials
are and will be indispensable as raw materials for medical devices because of
their electric conductivity, visibility under X-ray fluoroscopy, and other
favorable features. What is now desired is to develop a metallic material which
causes no artifacts during MRI. MATERIALS AND METHODS: In the present study, we
prepared a single-phase and homogeneous Au-Pt alloys (Au; diamagnetic metal, and
Pt; paramagnetic metal) by the processing of thermal treatment. Volume magnetic
susceptibility was measured with a SQUID Flux Meter and MRI artifact was
evaluated using a 1.5-T scanner. RESULTS: After final thermal treatment, an
entirely recrystallized homogeneous organization was noted. The Au-35Pt alloy was
shown to have a volume magnetic susceptibility of -8.8ppm, causing almost free
from artifacts during MRI. CONCLUSIONS: We thus prepared an Au-35Pt alloy which
had a magnetic susceptibility very close to that of living tissue and caused much
fewer artifacts during MRI. It is promising as a material for spinal cages,
intracranial electrodes, cerebral aneurysm embolization coils, markers for MRI
and so on.
PMID- 28700895
TI - Plasmablastic lymphoma presenting as exophytic skin lesions.
PMID- 28700896
TI - Assessing the Safety of Human Pluripotent Stem Cells and Their Derivatives for
Clinical Applications.
AB - Pluripotent stem cells may acquire genetic and epigenetic variants during culture
following their derivation. At a conference organized by the International Stem
Cell Initiative, and held at The Jackson Laboratory, Bar Harbor, Maine, October
2016, participants discussed how the appearance of such variants can be monitored
and minimized and, crucially, how their significance for the safety of
therapeutic applications of these cells can be assessed. A strong recommendation
from the meeting was that an international advisory group should be set up to
review the genetic and epigenetic changes observed in human pluripotent stem cell
lines and establish a framework for evaluating the risks that they may pose for
clinical use.
PMID- 28700897
TI - A systematic comparison of clinically viable nanomedicines targeting HMG-CoA
reductase in inflammatory atherosclerosis.
AB - Atherosclerosis is a leading cause of worldwide morbidity and mortality whose
management could benefit from novel targeted therapeutics. Nanoparticles are
emerging as targeted drug delivery systems in chronic inflammatory disorders. To
optimally exploit nanomedicines, understanding their biological behavior is
crucial for further development of clinically relevant and efficacious
nanotherapeutics intended to reduce plaque inflammation. Here, three clinically
relevant nanomedicines, i.e., high-density lipoprotein ([S]-HDL), polymeric
micelles ([S]-PM), and liposomes ([S]-LIP), that are loaded with the HMG-CoA
reductase inhibitor simvastatin [S], were evaluated in the apolipoprotein E
deficient (Apoe-/-) mouse model of atherosclerosis. We systematically employed
quantitative techniques, including in vivo positron emission tomography imaging,
gamma counting, and flow cytometry to evaluate the biodistribution,
nanomedicines' uptake by plaque-associated macrophages/monocytes, and their
efficacy to reduce macrophage burden in atherosclerotic plaques. The three
formulations demonstrated distinct biological behavior in Apoe-/- mice. While [S]
PM and [S]-LIP possessed longer circulation half-lives, the three platforms
accumulated to similar levels in atherosclerotic plaques. Moreover, [S]-HDL and
[S]-PM showed higher uptake by plaque macrophages in comparison to [S]-LIP, while
[S]-PM demonstrated the highest uptake by Ly6Chigh monocytes. Among the three
formulations, [S]-PM displayed the highest efficacy in reducing macrophage burden
in advanced atherosclerotic plaques. In conclusion, our data demonstrate that [S]
PM is a promising targeted drug delivery system, which can be advanced for the
treatment of atherosclerosis and other inflammatory disorders in the clinical
settings. Our results also emphasize the importance of a thorough understanding
of nanomedicines' biological performance, ranging from the whole body to the
target cells, as well drug retention in the nanoparticles. Such systematic
investigations would allow rational applications of nanomaterials', beyond
cancer, facilitating the expansion of the nanomedicine horizon.
PMID- 28700898
TI - Sub-100nm, long tumor retention SN-38-loaded photonic micelles for tri-modal
cancer therapy.
AB - The tumor penetration and accumulation of nanoparticle-based drug delivery
systems are highly dependent on the particle size. Nanomedicines in the sub-100nm
range have been suggested by previous studies to have superior antitumor efficacy
on various solid tumors. SN-38 is a very important and highly potent drug for
several cancers including colon cancer. However, due to the ultra-flat aromatic
structure of SN-38, it is typically very difficult to produce sub-100nm, SN-38
encapsulated nanoparticles without modification of the chemical structure. Here,
we report on the successful production of 20-30nm, SN-38-encapsulated photonic
micelles for effectively trimodal cancer therapy. Taking advantages of the
supramolecular "pi-pi" stacking and hydrophobicity interaction between SN-38, and
a unique class of photonic nanoporphyrin micelles (NPM), the extremely
hydrophobic SN-38 was successfully encapsulated into NPM with significantly
increased water solubility (up to 500 times). At equivalent dose of drug,
photosensitizer and light irradiation, combination therapy with SN-38
encapsulated nanoporphyrin micelles (SN-NPM) enhanced the in vitro antitumor
activity by 78 and 350 times over single treatment with SN-38 and phototherapy
alone, respectively. Due to the relatively small size, SN-NPM possessed superior
long tumor retention time (>5days) and much higher accumulation in tumors than in
normal organs, as shown by near-infrared fluorescence (NIRF) imaging.
Furthermore, the trimodal therapy (photothermal-, photodynamic- and chemo
therapy) with SN-NPM demonstrated dramatically enhanced in vivo antitumor
efficacy over single treatment on nude mice bearing HT-29 colon cancer xenograft.
Therefore, these sub-100nm, SN-38-encapsulated photonic micelles show great
promise for multimodal cancer therapy.
PMID- 28700899
TI - Pegylated liposomal formulation of doxorubicin overcomes drug resistance in a
genetically engineered mouse model of breast cancer.
AB - Success of cancer treatment is often hampered by the emergence of multidrug
resistance (MDR) mediated by P-glycoprotein (ABCB1/Pgp). Doxorubicin (DOX) is
recognized by Pgp and therefore it can induce therapy resistance in breast cancer
patients. In this study our aim was to evaluate the susceptibility of the
pegylated liposomal formulation of doxorubicin (PLD/Doxil(r)/Caelyx(r)) to MDR.
We show that cells selected to be resistant to DOX are cross-resistant to PLD and
PLD is also ineffective in an allograft model of doxorubicin-resistant mouse B
cell leukemia. In contrast, PLD was far more efficient than DOX as reflected by a
significant increase of both relapse-free and overall survival of Brca1-/-;p53-/-
mammary tumor bearing mice. Increased survival could be explained by the delayed
onset of drug resistance. Consistent with the higher Pgp levels needed to confer
resistance, PLD administration was able to overcome doxorubicin insensitivity of
the mouse mammary tumors. Our results indicate that the favorable
pharmacokinetics achieved with PLD can effectively overcome Pgp-mediated
resistance, suggesting that PLD therapy could be a promising strategy for the
treatment of therapy-resistant breast cancer patients.
PMID- 28700900
TI - Nanoparticles administered intrapericardially enhance payload myocardial
distribution and retention.
AB - Pharmacological therapies for cardiovascular diseases are limited by short-term
pharmacokinetics and extra-cardiac adverse effects. Improving delivery
selectivity specifically to the heart, wherein therapeutic drug levels can be
maintained over time, is highly desirable. Nanoparticle (NP)-based pericardial
drug delivery could provide a strategy to concentrate therapeutics within a
unique, cardiac-restricted compartment to allow sustained drug penetration into
the myocardium. Our objective was to explore the kinetics of myocardial
penetration and retention after pericardial NP drug delivery. Fluorescently
tagged poly(lactic-co-glycolic acid) (PLGA) NPs were loaded with BODIPY, a
fluorophore, and percutaneously administered into the pericardium via subxiphoid
puncture in rabbits. At distinct timepoints hearts were examined for presence of
NPs and BODIPY. PLGA NPs were found non-uniformly distributed on the epicardium
following pericardial administration, displaying a half-life of ~2.5days in the
heart. While NPs were mostly confined to epicardial layers, BODIPY was capable of
penetrating into the myocardium, resulting in a transmural gradient. The distinct
architecture and physiology of the different regions of the heart influenced
BODIPY distribution, with fluorophore penetrating more readily into atria than
ventricles. BODIPY proved to have a long-term presence within the heart, with a
half-life of ~7days. Our findings demonstrate the potential of utilizing the
pericardial space as a sustained drug-eluting reservoir through the application
of nanoparticle-based drug delivery, opening several exciting avenues for
selective and prolonged cardiac therapeutics.
PMID- 28700901
TI - Hyperspectral image analysis for rapid and accurate discrimination of bacterial
infections: A benchmark study.
AB - With the rapid diffusion of Full Laboratory Automation systems, Clinical
Microbiology is currently experiencing a new digital revolution. The ability to
capture and process large amounts of visual data from microbiological specimen
processing enables the definition of completely new objectives. These include the
direct identification of pathogens growing on culturing plates, with expected
improvements in rapid definition of the right treatment for patients affected by
bacterial infections. In this framework, the synergies between light spectroscopy
and image analysis, offered by hyperspectral imaging, are of prominent interest.
This leads us to assess the feasibility of a reliable and rapid discrimination of
pathogens through the classification of their spectral signatures extracted from
hyperspectral image acquisitions of bacteria colonies growing on blood agar
plates. We designed and implemented the whole data acquisition and processing
pipeline and performed a comprehensive comparison among 40 combinations of
different data preprocessing and classification techniques. High discrimination
performance has been achieved also thanks to improved colony segmentation and
spectral signature extraction. Experimental results reveal the high accuracy and
suitability of the proposed approach, driving the selection of most suitable and
scalable classification pipelines and stimulating clinical validations.
PMID- 28700902
TI - A novel algorithm to detect glaucoma risk using texton and local configuration
pattern features extracted from fundus images.
AB - Glaucoma is an optic neuropathy defined by characteristic damage to the optic
nerve and accompanying visual field deficits. Early diagnosis and treatment are
critical to prevent irreversible vision loss and ultimate blindness. Current
techniques for computer-aided analysis of the optic nerve and retinal nerve fiber
layer (RNFL) are expensive and require keen interpretation by trained
specialists. Hence, an automated system is highly desirable for a cost-effective
and accurate screening for the diagnosis of glaucoma. This paper presents a new
methodology and a computerized diagnostic system. Adaptive histogram equalization
is used to convert color images to grayscale images followed by convolution of
these images with Leung-Malik (LM), Schmid (S), and maximum response (MR4 and
MR8) filter banks. The basic microstructures in typical images are called
textons. The convolution process produces textons. Local configuration pattern
(LCP) features are extracted from these textons. The significant features are
selected using a sequential floating forward search (SFFS) method and ranked
using the statistical t-test. Finally, various classifiers are used for
classification of images into normal and glaucomatous classes. A high
classification accuracy of 95.8% is achieved using six features obtained from the
LM filter bank and the k-nearest neighbor (kNN) classifier. A glaucoma
integrative index (GRI) is also formulated to obtain a reliable and effective
system.
PMID- 28700903
TI - Computer-based classification of chromoendoscopy images using homogeneous texture
descriptors.
AB - Computer-aided analysis of clinical pathologies is a challenging task in the
field of medical imaging. Specifically, the detection of abnormal regions in the
frames collected during an endoscopic session is difficult. The variations in the
conditions of image acquisition, such as field of view or illumination
modification, make it more demanding. Therefore, the design of a computer
assisted diagnostic system for the recognition of gastric abnormalities requires
features that are robust to scale, rotation, and illumination variations of the
images. Therefore, this study focuses on designing a set of texture descriptors
based on the Gabor wavelets that will cope with certain image dynamics. The
proposed features are extracted from the images and utilized for the
classification of the chromoendoscopy (CH) frames into normal and abnormal
categories. Moreover, to attain a higher accuracy, an optimized subset of
descriptors is selected through the genetic algorithm. The results obtained using
the proposed features are compared with other existing texture descriptors (e.g.,
local binary pattern and homogeneous texture descriptors). Furthermore, the
selected features are used to train the support vector machine (SVM), naive Bayes
(NB) algorithm, k-nearest neighbor algorithm, linear discriminant analysis, and
ensemble tree classifier. The performance of these state-of-the-art classifiers
for different texture descriptors is compared based on the accuracy, sensitivity,
specificity, and area under the curve (AUC) derived by using the CH images. The
classification results reveal that the SVM classifier achieves 90.0% average
accuracy and 0.93 AUC when it is employed with an optimized set of features
obtained by using a genetic algorithm.
PMID- 28700904
TI - Inhibition of high glucose-induced inflammation and fibrosis by a novel curcumin
derivative prevents renal and heart injury in diabetic mice.
AB - Hyperglycemia-induced inflammation and fibrosis have important roles in the
pathogenesis of diabetic nephropathy and cardiomyopathy. With inflammatory
cytokines and signaling pathways as important mediators, targeting inflammation
may be an effective approach to new avenue for treating diabetic complications.
J17, a molecule with structural similarities to curcumin, exhibited good anti
inflammatory activities by inhibiting LPS-induced inflammatory response in
macrophages. However, its ability to alleviate hyperglycemia-induced injury via
its anti-inflammatory actions remained unclear. Thus, we reported that J17 exerts
significant inhibitory effects on hyperglycemia-induced inflammation and fibrosis
in NRK-52E cells, H9C2 cells and a streptozotocin-induced diabetic mouse model.
We also found that the anti-inflammatory and anti-fibrosis activities of J17 are
associated with the inhibition of the P38 and AKT signal pathway, respectively.
In vivo oral administration of J17 suppressed hyperglycemia-induced inflammation,
hypertrophy and fibrosis, thereby reducing key markers for renal and cardiac
dysfunction and improving in fibrosis and pathological changes in both renal and
cardiac tissues of diabetic mice. The results of this study indicated that J17
can be potentially used as a cardio- and reno-protective agent and that targeting
the P38 and AKT pathways may be an effective therapeutic strategy for diabetic
complications.
PMID- 28700905
TI - Chronic iron overload induces functional and structural vascular changes in small
resistance arteries via NADPH oxidase-dependent O2- production.
AB - Iron overload leads to excessive free radical formation and induces
cardiovascular dysfunction. Thus, our aim was to investigate the structural and
endothelial modulation of vascular tone induced by chronic iron overload in
mesenteric arteries. Rats were divided into two groups: the control (vehicle)
group and the group treated with iron dextran for 28days (100mg/kg, 5days a
week). Chronic iron overload altered the following morpho-physiological
parameters of third-order mesenteric resistance arteries: decreased lumen and
external diameters; increased wall/lumen ratio and wall thickness; decreased
distensibility and increased stiffness; and increased pulse wave velocity.
Additionally, iron overload increased the vasoconstrictor response in mesenteric
arterial rings in vitro but did not affect the relaxation induced by
acetylcholine and sodium nitroprusside. It is suggested that iron overload
reduces nitric oxide bioavailability by increasing free radicals, because L-NAME
did not shift the concentration-response curve to phenylephrine, but L-NAME plus
superoxide dismutase shifted the curve to the left. In vitro assays with DAF-2
and DHE indicated reduced NO production and increased superoxide anion (O2-)
generation in the iron-overloaded group. Furthermore, tiron, catalase, apocynin
and losartan induced reduced reactivity only in iron-overloaded rats. Moreover,
increased ACE activity was observed in the mesenteric resistance arteries of iron
overloaded rats accompanied by an increase in gp91phox, catalase, ERK1/2 and eNOS
protein expression. In conclusion, these findings show that chronic iron overload
induces structural and functional changes in resistance arteries, most likely due
to a decrease in NO bioavailability resulting from an increase in O2- production
by NADPH oxidase.
PMID- 28700906
TI - Vitamin D deficiency impairs neurobehavioral development in male mice.
AB - Vitamin D deficiency is prevalent especially in pregnant women and children.
Several studies found that vitamin D status was negatively correlated with risk
of senile neurobehavioral abnormality. The aim of this study was to investigate
the effects of vitamin D deficiency on neurobehavioral development in mice. In
vitamin D deficiency group, dams and their male pups were fed with vitamin D
deficient (VDD) diet, in which vitamin D was depleted. Anxiety-related behavior,
depressive-like behavior, spatial learning and memory were measured. As expected,
serum 25(OH)D level was reduced in VDD diet-fed mice. An anhedonia state, a key
depressive-like behavior, was observed in VDD diet-fed mice. In open-field test,
peripheral time was decreased and internal time was increased in VDD diet-fed
mice. In elevated plus maze, the latency of the first entry into open arms was
increased and the number of crossing in open arms was elevated in VDD diet-fed
mice. Morris Water Maze showed that VDD-fed mice showed longer escape latency in
the first six days. On the seventh day, escape latency was increased in VDD diet
fed mice. These results provide evidence that vitamin D deficiency impairs
neurobehavioral development.
PMID- 28700907
TI - Antimicrobial Peptides in the Cross Hairs of Computer Simulations.
PMID- 28700908
TI - Endothelial Glycocalyx-Mediated Nitric Oxide Production in Response to Selective
AFM Pulling.
AB - Nitric oxide (NO) is a regulatory molecule in the vascular system and its
inhibition due to endothelial injury contributes to cardiovascular disease. The
glycocalyx is a thin layer of glycolipids, glycoproteins, and proteoglycans on
the surface of mammalian epithelial cells. Extracellular forces are transmitted
through the glycocalyx to initiate intracellular signaling pathways. In
endothelial cells (ECs), previous studies have shown the glycocalyx to be a
significant mediator of NO production; degradation of the endothelial glycocalyx
layer (EGL) drastically reduces EC production of NO in response to fluid shear
stress. However, the specific EGL components involved in this process are not
well established. Recent work using short-hairpin RNA approaches in vitro suggest
that the proteoglycan glypican-1, not syndecan-1, is the dominant core protein
mediating shear-induced NO production. We utilized atomic force microscopy (AFM)
to apply force selectively to components of the EGL of confluent rat fat pad ECs
(RFPECs), including proteoglycans and glycosaminoglycans, to observe how each
component individually contributes to force-induced production of NO. 4,5
diaminofluorescein diacetate, a cell-permeable fluorescent molecule, was used to
detect changes in intracellular NO production. Antibody-coated AFM probes
exhibited strong surface binding to RFPEC monolayers, with 100-300 pN mean
adhesion forces. AFM pulling on glypican-1 and heparan sulfate for 10 min caused
significantly increased NO production, whereas pulling on syndecan-1, CD44,
hyaluronic acid, and with control probes did not. We conclude that AFM pulling
can be used to activate EGL-mediated NO production and that the heparan sulfate
proteoglycan glypican-1 is a primary mechanosensor for shear-induced NO
production.
PMID- 28700909
TI - Assessing the Collective Dynamics of Motile Cilia in Cultures of Human Airway
Cells by Multiscale DDM.
AB - The technique of differential dynamic microscopy is extended here, showing that
it can provide a powerful and objective method of video analysis for optical
microscopy videos of in vitro samples of live human bronchial epithelial ciliated
cells. These cells are multiciliated, with motile cilia that play key
physiological roles. It is shown that the ciliary beat frequency can be recovered
to match conventional analysis, but in a fully automated fashion. Furthermore, it
is shown that the properties of spatial and temporal coherence of cilia beat can
be recovered and distinguished, and that if a collective traveling wave (the
metachronal wave) is present, this has a distinct signature and its wavelength
and direction can be measured.
PMID- 28700910
TI - Catch Bonds at T Cell Interfaces: Impact of Surface Reorganization and Membrane
Fluctuations.
AB - Catch bonds are characterized by average lifetimes that initially increase with
increasing tensile force. Recently, they have been implicated in T cell
activation, where small numbers of antigenic receptor-ligand bonds at a cell-cell
interface can stimulate a T cell. Here, we use computational methods to
investigate small numbers of bonds at the interface between two membranes. We
characterize the time-dependent forces on the bonds in response to changes in the
membrane shape and the organization of other surface molecules. We then determine
the distributions of bond lifetimes using recent force-dependent lifetime data
for T cell receptors bound to various ligands. Strong agonists, which exhibit
catch bond behavior, are markedly more likely to remain intact than an antagonist
whose average lifetime decreases with increasing force. Thermal fluctuations of
the membrane shape enhance the decay of the average force on a bond, but also
lead to fluctuations of the force. These fluctuations promote bond rupture, but
the effect is buffered by catch bonds. When more than one bond is present, the
bonds experience reduced average forces that depend on their relative positions,
leading to changes in bond lifetimes. Our results highlight the importance of
force-dependent binding kinetics when bonds experience time-dependent and
fluctuating forces, as well as potential consequences of collective bond behavior
relevant to T cell activation.
PMID- 28700911
TI - Non-equilibrium Membrane Homeostasis in Expanding Cellular Domains.
AB - Many cell behaviors involve cell-shape transformations that impose considerable
changes in the cell's surface area, requiring a constant adaptation of the cell's
plasma membrane area to prevent cell lysis. Here, we theoretically describe the
interplay between the plasma membrane dynamics and a physically connected cell
cortex or wall, accounting for spatial variations in membrane recycling and
tension. In-plane membrane net flows result naturally from these dynamics and, in
the presence of an expanding cell cortex or wall, regions of converging or
diverging flow patterns emerge. These flow patterns can potentially explain the
spatial localization/segregation of membrane proteins in processes such as cell
polarization. We also identify the relevant parameters that control membrane
homeostasis and derive the range of parameters for which homeostatic states
exist.
PMID- 28700912
TI - Quantitative Brightness Analysis of Protein Oligomerization in the Nuclear
Envelope.
AB - Brightness analysis of fluorescence fluctuation experiments has been used to
successfully measure the oligomeric state of proteins at the plasma membrane, in
the nucleoplasm, and in the cytoplasm of living cells. Here we extend brightness
analysis to the nuclear envelope (NE), a double membrane barrier separating the
cytoplasm from the nucleoplasm. Results obtained by applying conventional
brightness analysis to fluorescently tagged proteins within the NE exhibited an
unusual concentration dependence. Similarly, the autocorrelation function of the
fluorescence fluctuations exhibited unexpected changes with protein
concentration. These observations motivated the application of mean-segmented Q
analysis, which identified the existence of a fluctuation process distinct from
molecular diffusion in the NE. We propose that small changes in the separation of
the inner and outer nuclear membrane are responsible for the additional
fluctuation process, as suggested by results obtained for luminal and nuclear
membrane-associated EGFP-tagged proteins. Finally, we applied these insights to
study the oligomerization of the luminal domains of two nuclear membrane
proteins, nesprin-2 and SUN2, which interact transluminally to form a nuclear
envelope-spanning linker molecular bridge known as the linker of the
nucleoskeleton and cytoskeleton complex.
PMID- 28700913
TI - Impact of Zygosity on Bimodal Phenotype Distributions.
AB - Allele number, or zygosity, is a clear determinant of gene expression in diploid
cells. However, the relationship between the number of copies of a gene and its
expression can be hard to anticipate, especially when the gene in question is
embedded in a regulatory circuit that contains feedback. Here, we study this
question making use of the natural genetic variability of human populations,
which allows us to compare the expression profiles of a receptor protein in
natural killer cells among donors infected with human cytomegalovirus with one or
two copies of the allele. Crucially, the distribution of gene expression in many
of the donors is bimodal, which indicates the presence of a positive feedback
loop somewhere in the regulatory environment of the gene. Three separate gene
circuit models differing in the location of the positive feedback loop with
respect to the gene can all reproduce the homozygous data. However, when the
resulting fitted models are applied to the hemizygous donors, one model (the one
with the positive feedback located at the level of gene transcription) is
superior in describing the experimentally observed gene-expression profile. In
that way, our work shows that zygosity can help us relate the structure and
function of gene regulatory networks.
PMID- 28700914
TI - Period Robustness and Entrainability of the Kai System to Changing Nucleotide
Concentrations.
AB - Circadian clocks must be able to entrain to time-varying signals to keep their
oscillations in phase with the day-night rhythm. On the other hand, they must
also exhibit input compensation: their period must remain approximately one day
in different constant environments. The posttranslational oscillator of the Kai
system can be entrained by transient or oscillatory changes in the ATP fraction,
yet is insensitive to constant changes in this fraction. We study in three
different models of this system how these two seemingly conflicting criteria are
met. We find that one of these (our recently published Paijmans model) exhibits
the best tradeoff between input compensation and entrainability: on the footing
of equal phase-response curves, it exhibits the strongest input compensation.
Performing stochastic simulations at the level of individual hexamers allows us
to identify a new, to our knowledge, mechanism, which is employed by the Paijmans
model to achieve input compensation: at lower ATP fraction, the individual
hexamers make a shorter cycle in the phosphorylation state space, which
compensates for the slower pace at which they traverse the cycle.
PMID- 28700915
TI - A Model for Adult Organ Resizing Demonstrates Stem Cell Scaling through a Tunable
Commitment Rate.
AB - Many adult organs grow or shrink to accommodate different physiological demands.
Often, as total cell number changes, stem cell number changes proportionally in a
phenomenon called "stem cell scaling". The cellular behaviors that give rise to
scaling are unknown. Here we study two complementary theoretical models of the
adult Drosophila midgut, a stem cell-based organ with known resizing dynamics.
First, we derive a differential equations model of midgut resizing and show that
the in vivo kinetics of growth can be recapitulated if the rate of fate
commitment depends on the tissue's stem cell proportion. Second, we develop a 2D
simulation of the midgut and find that proportion-dependent commitment rate and
stem cell scaling can arise phenomenologically from the stem cells' exploration
of physical tissue space during its lifetime. Together, these models provide a
biophysical understanding of how stem cell scaling is maintained during organ
growth and shrinkage.
PMID- 28700916
TI - A Reaction-Diffusion Model Explains Amplification of the PLC/PKC Pathway in
Fibroblast Chemotaxis.
AB - During the proliferative phase of cutaneous wound healing, dermal fibroblasts are
recruited into the clotted wound by a concentration gradient of platelet-derived
growth factor (PDGF), together with other spatial cues. Despite the importance of
this chemotactic process, the mechanisms controlling the directed migration of
slow-moving mesenchymal cells such as fibroblasts are not well understood. Here,
we develop and analyze a reaction-diffusion model of phospholipase C/protein
kinase C (PKC) signaling, which was recently identified as a requisite PDGF
gradient-sensing pathway, with the goal of identifying mechanisms that can
amplify its sensitivity in the shallow external gradients typical of chemotaxis
experiments. We show that phosphorylation of myristoylated alanine-rich C kinase
substrate by membrane-localized PKC constitutes a positive feedback that is
sufficient for local pathway amplification. The release of phosphorylated
myristoylated alanine-rich C kinase substrate and its subsequent diffusion and
dephosphorylation in the cytosol also serves to suppress the pathway in down
gradient regions of the cell. By itself, this mechanism only weakly amplifies
signaling in a shallow PDGF gradient, but it synergizes with other feedback
mechanisms to enhance amplification. This model offers a framework for a
mechanistic understanding of phospholipase C/PKC signaling in chemotactic
gradient sensing and can guide the design of experiments to assess the roles of
putative feedback loops.
PMID- 28700917
TI - Structure and Dynamics of DNA and RNA Double Helices of CAG and GAC Trinucleotide
Repeats.
AB - CAG trinucleotide repeats are known to cause 10 late-onset progressive
neurodegenerative disorders as the repeats expand beyond a threshold, whereas GAC
repeats are associated with skeletal dysplasias and expand from the normal five
to a maximum of seven repeats. The TR secondary structure is believed to play a
role in CAG expansions. We have carried out free energy and molecular dynamics
studies to determine the preferred conformations of the A-A noncanonical pairs in
(CAG)n and (GAC)n trinucleotide repeats (n = 1, 4) and the consequent changes in
the overall structure of the RNA and DNA duplexes. We find that the global free
energy minimum corresponds to A-A pairs stacked inside the core of the helix with
anti-anti conformations in RNA and (high-anti)-(high-anti) conformations in DNA.
The next minimum corresponds to anti-syn conformations, whereas syn-syn
conformations are higher in energy. Transition rates of the A-A conformations are
higher for RNA than DNA. Mechanisms for these various transitions are identified.
Additional structural and dynamical aspects of the helical conformations are
explored, with a focus on contrasting CAG and GAC duplexes. The neutralizing ion
distribution around the noncanonical pairs is described.
PMID- 28700918
TI - Dynamic Model Exposes the Energetics and Dynamics of the Injection Machinery for
Bacteriophage T4.
AB - Bacteriophage T4 infects the bacterial host (Escherichia coli) using an efficient
genomic delivery machine that is driven by elastic energy stored in a contractile
tail sheath. Although the atomic structure of T4 is largely known, the dynamics
of its fascinating injection machinery is not understood. This article
contributes, to our knowledge, the first predictions of the energetics and
dynamics of the T4 injection machinery using a novel dynamic model. The model
employs an atomistic (molecular dynamics) representation of a fraction of the
sheath structure to generate a continuum model of the entire sheath that also
couples to a model of the viral capsid and tail tube. The resulting model of the
entire injection machine reveals estimates for the energetics, timescale, and
pathway of the T4 injection process as well as the force available for cell
rupture. It also reveals the large and highly nonlinear conformational changes of
the sheath whose elastic energy drives the injection process.
PMID- 28700919
TI - Translating ceRNA Susceptibilities into Correlation Functions.
AB - Competition to bind microRNAs induces an effective positive cross talk between
their targets, which are therefore known as "competing endogenous RNAs" (ceRNAs).
Although such an effect is known to play a significant role in specific
situations, estimating its strength from data and experimentally in physiological
conditions appears to be far from simple. Here, we show that the susceptibility
of ceRNAs to different types of perturbations affecting their competitors (and
hence their tendency to cross talk) can be encoded in quantities as intuitive and
as simple to measure as correlation functions. This scenario is confirmed by
extensive numerical simulations and validated by re-analyzing phosphatase and
tensin homolog's cross-talk pattern from The Cancer Genome Atlas breast cancer
database. These results clarify the links between different quantities used to
estimate the intensity of ceRNA cross talk and provide, to our knowledge, new
keys to analyze transcriptional data sets and effectively probe ceRNA networks in
silico.
PMID- 28700920
TI - Modeling Endoplasmic Reticulum Network Maintenance in a Plant Cell.
AB - The endoplasmic reticulum (ER) in plant cells forms a highly dynamic network of
complex geometry. ER network morphology and dynamics are influenced by a number
of biophysical processes, including filament/tubule tension, viscous forces,
Brownian diffusion, and interactions with many other organelles and cytoskeletal
elements. Previous studies have indicated that ER networks can be thought of as
constrained minimal-length networks acted on by a variety of forces that perturb
and/or remodel the network. Here, we study two specific biophysical processes
involved in remodeling. One is the dynamic relaxation process involving a
combination of tubule tension and viscous forces. The other is the rapid creation
of cross-connection tubules by direct or indirect interactions with cytoskeletal
elements. These processes are able to remodel the ER network: the first reduces
network length and complexity whereas the second increases both. Using live cell
imaging of ER network dynamics in tobacco leaf epidermal cells, we examine these
processes on ER network dynamics. Away from regions of cytoplasmic streaming, we
suggest that the dynamic network structure is a balance between the two
processes, and we build an integrative model of the two processes for network
remodeling. This model produces quantitatively similar ER networks to those
observed in experiments. We use the model to explore the effect of parameter
variation on statistical properties of the ER network.
PMID- 28700921
TI - Retraction Notice to: Protonation State-Dependent Communication in Cytochrome c
Oxidase.
PMID- 28700922
TI - The Functional Amyloid Orb2A Binds to Lipid Membranes.
AB - Lipid membranes interact with and influence the aggregation of many amyloid
forming proteins. Orb2 is a cytoplasmic polyadenylation element-binding protein
homolog in Drosophila melanogaster that forms functional amyloids necessary for
long-term memory. One isoform, Orb2A, has a unique N-terminus that has been shown
to be important for the formation of amyloid-like aggregates and long-term memory
in vivo. Orb2A is also found enriched in the synaptic membrane fraction. Our
sequence and hydropathy analysis suggests that it can form an amphipathic helix,
which is ideal for lipid membrane interaction. We used circular dichroism and
site-directed spin labeling coupled with electron paramagnetic resonance to test
the first 88 amino acids of Orb2A for lipid interaction. We show that Orb2A1-88
interacts with anionic lipid membranes using an amphipathic helix at its unique N
terminus. This interaction depends on the charge of the lipid membrane and the
degree of membrane curvature. We used transmission electron microscopy and
electron paramagnetic resonance to show that the presence of anionic small
unilamellar vesicles inhibits amyloid fibril formation by Orb2A. This inhibition
by anionic membranes could be a potential mechanism regulating Orb2A amyloid
formation in vivo.
PMID- 28700923
TI - How Viruses Enter Cells: A Story behind Bacteriophage T4.
PMID- 28700924
TI - Mesoscopic Adaptive Resolution Scheme toward Understanding of Interactions
between Sickle Cell Fibers.
AB - Understanding of intracellular polymerization of sickle hemoglobin (HbS) and
subsequent interaction with the membrane of a red blood cell (RBC) is important
to predict the altered morphologies and mechanical properties of sickle RBCs in
sickle cell anemia. However, modeling the integrated processes of HbS nucleation,
polymerization, HbS fiber interaction, and subsequent distortion of RBCs is
challenging as they occur at multispatial scales, ranging from nanometers to
micrometers. To make progress toward simulating the integrated processes, we
propose a hybrid HbS fiber model, which couples fine-grained and coarse-grained
HbS fiber models through a mesoscopic adaptive resolution scheme (MARS). To this
end, we apply a microscopic model to capture the dynamic process of
polymerization of HbS fibers, while maintaining the mechanical properties of
polymerized HbS fibers by the mesoscopic model, thus providing a means of
bridging the subcellular and cellular phenomena in sickle cell disease. At the
subcellular level, this model can simulate HbS polymerization with preexisting
HbS nuclei. At the cellular level, if combined with RBC models, the generated HbS
fibers could be applied to study the morphologies and membrane stiffening of
sickle RBCs. One important feature of the MARS is that it can be easily employed
in other particle-based multiscale simulations where a dynamic coarse-graining
and force-blending method is required. As demonstrations, we first apply the
hybrid HbS fiber model to simulate the interactions of two growing fibers and
find that their final configurations depend on the orientation and interaction
distance between two fibers, in good agreement with experimental observations. We
also model the formation of fiber bundles and domains so that we explore the
mechanism that causes fiber branching.
PMID- 28700925
TI - Protein Transport by the Nuclear Pore Complex: Simple Biophysics of a Complex
Biomachine.
AB - In eukaryotic cells, transport of molecules between the nucleus and the cytoplasm
is facilitated by highly selective and efficient biomachines known as nuclear
pore complexes (NPCs). The structural details of NPCs vary across species, with
many of their constituent proteins exhibiting relatively low sequence
conservation; yet the NPC as a whole retains its general architecture and
mechanism of action in all eukaryotes from yeast to humans. This functional
conservation in the absence of precise molecular conservation suggests that many
aspects of the NPC transport mechanism may be understood based on general
biophysical considerations. Accordingly, some aspects of NPC function have been
recapitulated in artificial nanochannel mimics, even though they lack certain
molecular elements of the endogenous NPC. Herein, we review biophysical aspects
of NPC architecture and function and cover recent progress in the field. We also
review recent advances in man-made molecular filters inspired by NPCs, and their
applications in nanotechnology. We conclude the review with an outlook on
outstanding questions in the field and biomedical aspects of NPC transport.
PMID- 28700926
TI - The Energetics of Chromophore Binding in the Visual Photoreceptor Rhodopsin.
AB - The visual photoreceptor rhodopsin is a prototypical G-protein-coupled receptor
(GPCR) that stabilizes its inverse agonist ligand, 11-cis-retinal (11CR), by a
covalent, protonated Schiff base linkage. In the visual dark adaptation, the
fundamental molecular event after photobleaching of rhodopsin is the
recombination reaction between its apoprotein opsin and 11CR. Here we present a
detailed analysis of the kinetics and thermodynamics of this reaction, also known
as the "regeneration reaction". We compared the regeneration of purified
rhodopsin reconstituted into phospholipid/detergent bicelles with rhodopsin
reconstituted into detergent micelles. We found that the lipid bilayer of
bicelles stabilized the chromophore-free opsin over the long timescale required
for the regeneration experiments, and also facilitated the ligand reuptake
binding reaction. We utilized genetic code expansion and site-specific
bioorthogonal labeling of rhodopsin with Alexa488 to enable, to our knowledge, a
novel fluorescence resonance energy transfer-based measurement of the binding
kinetics between opsin and 11CR. Based on these results, we report a complete
energy diagram for the regeneration reaction of rhodopsin. We show that the
dissociation reaction of rhodopsin to 11CR and opsin has a 25-pM equilibrium
dissociation constant, which corresponds to only 0.3 kcal/mol stabilization
compared to the noncovalent, tightly bound antagonist-GPCR complex of
iodopindolol and beta-adrenergic receptor. However, 11CR dissociates four orders
of-magnitude slower than iodopindolol, which corresponds to a 6-kcal/mol higher
dissociation free energy barrier. We further used isothermal titration
calorimetry to show that ligand binding in rhodopsin is enthalpy driven with -22
kcal/mol, which is 12 kcal/mol more stable than the antagonist-GPCR complex. Our
data provide insights into the ligand-receptor binding reaction for rhodopsin in
particular, and for GPCRs more broadly.
PMID- 28700927
TI - Charged Antimicrobial Peptides Can Translocate across Membranes without Forming
Channel-like Pores.
AB - How can highly charged, cationic antimicrobial peptides (AMPs) translocate across
hydrophobic lipid bilayers despite the prohibitive energetic penalty to do so? A
common explanation has been the formation of peptide-lined channels. However, for
most AMPs, no structures of membrane pores have been found despite clear evidence
of membrane leakage and antimicrobial activity. The study here suggests an
alternative and simple reason: for the AMP PGLa from Xenopus laevis (charge +5),
such pores are not needed to explain both leakage and peptide translocation.
Elevated-temperature multimicrosecond equilibrium simulations at all-atomistic
level reveal that peptides spontaneously translocate across the membrane
individually on a timescale of tens of microseconds, without forming pores. Both
surface-bound peptides and lipids assist in the one-by-one translocation of the
charged side chains. Single peptides can remain in a transmembrane orientation
for many microseconds, snorkeling some charged residues to one interface and some
to the opposite, but without inducing a water channel. Instead of stable pores,
short-lived water bridges occur when two or three peptides connect at their
termini, allowing both ion translocation and lipid flip-flop via a brushlike
mechanism usually involving the C terminus of one peptide. The results here
suggest that for some specific antimicrobial and other membrane active peptides,
pore formation may not have to be invoked at all to explain peptide translocation
and membrane permeabilization, which may explain why no channel structures for
them have been determined experimentally.
PMID- 28700928
TI - Molecular State of the Membrane-Active Antibiotic Daptomycin.
AB - Membrane-active antibiotics are potential alternatives to the resistance-prone
conventional antibiotics. Daptomycin, a cyclic lipopeptide, is the only membrane
active antibiotic approved by the U.S. Food and Drug Administration so far. The
drug interacts with the cytoplasmic membranes of Gram-positive pathogens, causing
membrane permeabilization to ions and cell death. The antibiotic activity is
calcium-ion dependent and correlates with the target membrane's content of
phosphatidylglycerol (PG). For such a complex reaction with membranes, it has
been difficult to uncover the molecular process that underlies its antibacterial
activity. The role of the cofactor, calcium ions, has been confusing. Many have
proposed that calcium ions binding to daptomycin is a precondition for membrane
interaction. Here, we report our findings on the molecular state of daptomycin
before and after its membrane-binding reaction, particularly at therapeutic
concentrations in the low micromolar range. We were able to perform small-angle x
ray scattering at sufficiently low daptomycin concentrations to determine that
the molecules are monomeric before membrane binding. By careful circular
dichroism (CD) analyses of daptomycin with Ca2+ and PG-containing membranes, we
found that there are only two states identifiable by CD, one before and another
after membrane binding; all other CD spectra are linear combinations of the two.
Before membrane binding, the molecular state of daptomycin as defined by CD is
the same with or without calcium ions. We are able to determine the
stoichiometric ratios of the membrane-binding reaction. The stoichiometric ratio
of daptomycin to calcium is 2:3. The stoichiometric ratio of daptomycin to PG is
~1:1 if only the PG lipids in the outer leaflets of membranes are accessible to
daptomycin.
PMID- 28700930
TI - Greetings from Your New Editor-in-Chief.
PMID- 28700929
TI - A Cardiomyopathy Mutation in the Myosin Essential Light Chain Alters Actomyosin
Structure.
AB - We have used site-directed time-resolved fluorescence resonance energy transfer
to determine the effect of a pathological mutation in the human ventricular
essential light chain (hVELC) of myosin, on the structural dynamics of the actin
myosin complex. The hVELC modulates the function of actomyosin, through the
interaction of its N-terminal extension with actin and its C-terminal lobe with
the myosin heavy chain. Several mutations in hVELC are associated with
hypertrophic cardiomyopathy (HCM). Some biochemical effects of these mutations
are known, but further insight is needed about their effects on the structural
dynamics of functioning actomyosin. Therefore, we introduced the HCM mutation
E56G into a single-cysteine (C16) hVELC construct and substituted it for the VELC
of bovine cardiac myosin subfragment 1. Using a donor fluorescent probe on actin
(at C374) and an acceptor probe on C16 of hVELC, we performed time-resolved
fluorescence resonance energy transfer, directly detecting structural changes
within the bound actomyosin complex during function. The E56G mutation has no
significant effect on actin-activated ATPase activity or actomyosin affinity in
the presence of ATP, or on the structure of the strong-binding S complex in the
absence of ATP. However, in the presence of saturating ATP, where both W
(prepowerstroke) and S (postpowerstroke) structural states are observed, the
mutant increases the mole fraction of the S complex (increasing the duty ratio),
while shifting the structure of the remaining W complex toward that of S,
indicating a structural redistribution toward the strongly bound (force
generating) complex. We propose that this effect is responsible for the
hypercontractile phenotype induced by this HCM mutation in myosin.
PMID- 28700931
TI - Feedback Inhibition of the Rag GTPase GAP Complex Lst4-Lst7 Safeguards TORC1 from
Hyperactivation by Amino Acid Signals.
AB - Amino acids stimulate the eukaryotic target of rapamycin complex 1 (TORC1), and
hence growth, through the Rag GTPases and their regulators. Among these, the
yeast Lst4-Lst7 Rag GTPase GAP complex clusters, as we previously reported, at
the vacuolar membrane upon amino acid starvation. In response to amino acid
refeeding, it activates the Rag GTPase-TORC1 branch and is then dispersed from
the vacuolar surface. Here, we show that the latter effect is driven by TORC1
itself, which directly phosphorylates several residues within the intra-DENN loop
of Lst4 that, only in its non-phosphorylated state, tethers the Lst4-Lst7 complex
to the vacuolar membrane. An Lst4 variant disrupting this feedback inhibition
mechanism causes TORC1 hyperactivation and proliferation defects in cells grown
on poor nitrogen sources. Thus, we identify Lst4 as a TORC1 target and key node
of a homeostatic mechanism that adjusts TORC1 activity to the availability of
amino acids.
PMID- 28700932
TI - Selectively Impaired Endocannabinoid-Dependent Long-Term Depression in the
Lateral Habenula in an Animal Model of Depression.
AB - Abnormal potentiation in the lateral habenula (LHb) has been suggested to mediate
depression-like behaviors. However, the underlying mechanisms of the synaptic
efficacy regulation of LHb synapses and the potential for their modulation are
only poorly understood. Here, we report that long-term synaptic depression (LTD)
occurs in the LHb upon both low-frequency stimulation (LFS) and moderate
frequency stimulation (MFS). LFS-induced LTD (LFS-LTD) is accompanied by a
reduction in presynaptic release probability, which is endocannabinoid (eCB)
signaling dependent. Surprisingly, exposure to an acute stressor completely masks
the induction of LFS-LTD in the LHb while leaving the MFS-induced LTD intact.
Pharmacological activation of cannabinoid receptor 1 (CB1R) or blockade of
alphaCaMKII successfully restored LTD in the LHb in an animal model of
depression. Thus, our findings reveal a form of synaptic strength regulation and
a stress-induced shift of synaptic plasticity in the LHb.
PMID- 28700933
TI - Inhibition of RIF1 by SCAI Allows BRCA1-Mediated Repair.
AB - DNA double-strand breaks (DSBs) are repaired by either the homology-directed
repair (HDR) or the non-homologous end-joining (NHEJ) pathway. RIF1 (RAP1
interacting factor homolog) was recently shown to stimulate NHEJ through an
interaction with 53BP1 (p53-binding protein 1) phosphorylated at S/TQ sites, but
the molecular mechanism underlying pathway choice remains unclear. Here, we show
that SCAI (suppressor of cancer cell invasion) binds to 53BP1 phosphorylated at
S/TP sites and facilitates HDR. Upon DNA damage, RIF1 immediately accumulates at
damage sites and then gradually dissociates from 53BP1 and is subsequently
replaced with SCAI. Depletion of SCAI reduces both the accumulation of HDR
factors, including BRCA1 (breast cancer susceptibility gene 1), at damage sites
and the efficiency of HDR, as detected by a reporter assay system. These data
suggest that SCAI inhibits RIF1 function to allow BRCA1-mediated repair, which
possibly includes alt-NHEJ and resection-dependent NHEJ in G1, as well as HDR in
S/G2.
PMID- 28700934
TI - Parvalbumin-Expressing GABAergic Neurons in Primary Motor Cortex Signal Reaching.
AB - The control of targeted reaching is thought to be shaped by distinct subtypes of
local GABAergic inhibitory neurons in primary forelimb motor cortex (M1).
However, little is known about their action potential firing dynamics during
reaching. To address this, we recorded the activity of parvalbumin-expressing
(PV+) GABAergic neurons identified from a larger population of fast-spiking units
and putative excitatory regular-spiking units in layer 5 of the mouse forelimb M1
during an M1-dependent, sensory-triggered reaching task. PV+ neurons showed short
latency responses to the acoustic cue and vibrotactile trigger stimulus and an
increase in firing at reaching onset that scaled with the amplitude of reaching.
Unexpectedly, PV+ neurons fired before regular-spiking units at reach onset and
showed high overall firing rates during both sensory-triggered and spontaneous
reaches. Our data suggest that increasing M1 PV+ neuron firing rates may play a
role in the initiation of voluntary reaching.
PMID- 28700935
TI - Deletion of Type 2 Metabotropic Glutamate Receptor Decreases Sensitivity to
Cocaine Reward in Rats.
AB - Cocaine users show reduced expression of the metabotropic glutamate receptor
(mGluR2), but it is not clear whether this is a predisposing trait for addiction
or a consequence of drug exposure. In this study, we found that a nonsense
mutation at the mGluR2 gene decreased mGluR2 expression and altered the seeking
and taking of cocaine. mGluR2 mutant rats show reduced sensitivity to cocaine
reward, requiring more cocaine to reach satiation when it was freely available
and ceasing their drug-seeking behavior sooner than controls when the response
requirement was increased. mGluR2 mutant rats also show a lower propensity to
relapse after a period of cocaine abstinence, an effect associated with reduced
cocaine-induced dopamine and glutamate overflow in the nucleus accumbens. These
findings suggest that mGluR2 polymorphisms or reduced availability of mGluR2
might be risk factors for the initial development of cocaine use but could
actually protect against addiction by reducing sensitivity to cocaine reward.
PMID- 28700936
TI - Alternative Splicing of P/Q-Type Ca2+ Channels Shapes Presynaptic Plasticity.
AB - Alternative splicing of pre-mRNAs is prominent in the mammalian brain, where it
is thought to expand proteome diversity. For example, alternative splicing of
voltage-gated Ca2+ channel (VGCC) alpha1 subunits can generate thousands of
isoforms with differential properties and expression patterns. However, the
impact of this molecular diversity on brain function, particularly on synaptic
transmission, which crucially depends on VGCCs, is unclear. Here, we investigate
how two major splice isoforms of P/Q-type VGCCs (Cav2.1[EFa/b]) regulate
presynaptic plasticity in hippocampal neurons. We find that the efficacy of P/Q
type VGCC isoforms in supporting synaptic transmission is markedly different,
with Cav2.1[EFa] promoting synaptic depression and Cav2.1[EFb] synaptic
facilitation. Following a reduction in network activity, hippocampal neurons
upregulate selectively Cav2.1[EFa], the isoform exhibiting the higher synaptic
efficacy, thus effectively supporting presynaptic homeostatic plasticity.
Therefore, the balance between VGCC splice variants at the synapse is a key
factor in controlling neurotransmitter release and presynaptic plasticity.
PMID- 28700937
TI - DeltaFosB Regulates Gene Expression and Cognitive Dysfunction in a Mouse Model of
Alzheimer's Disease.
AB - Alzheimer's disease (AD) is characterized by cognitive decline and 5- to 10-fold
increased seizure incidence. How seizures contribute to cognitive decline in AD
or other disorders is unclear. We show that spontaneous seizures increase
expression of DeltaFosB, a highly stable Fos-family transcription factor, in the
hippocampus of an AD mouse model. DeltaFosB suppressed expression of the
immediate early gene c-Fos, which is critical for plasticity and cognition, by
binding its promoter and triggering histone deacetylation. Acute histone
deacetylase (HDAC) inhibition or inhibition of DeltaFosB activity restored c-Fos
induction and improved cognition in AD mice. Administration of seizure-inducing
agents to nontransgenic mice also resulted in DeltaFosB-mediated suppression of c
Fos, suggesting that this mechanism is not confined to AD mice. These results
explain observations that c-Fos expression increases after acute neuronal
activity but decreases with chronic activity. Moreover, these results indicate a
general mechanism by which seizures contribute to persistent cognitive deficits,
even during seizure-free periods.
PMID- 28700938
TI - Golgi Outpost Synthesis Impaired by Toxic Polyglutamine Proteins Contributes to
Dendritic Pathology in Neurons.
AB - Dendrite aberration is a common feature of neurodegenerative diseases caused by
protein toxicity, but the underlying mechanisms remain largely elusive. Here, we
show that nuclear polyglutamine (polyQ) toxicity resulted in defective terminal
dendrite elongation accompanied by a loss of Golgi outposts (GOPs) and a
decreased supply of plasma membrane (PM) in Drosophila class IV dendritic
arborization (da) (C4 da) neurons. mRNA sequencing revealed that genes
downregulated by polyQ proteins included many secretory pathway-related genes,
including COPII genes regulating GOP synthesis. Transcription factor enrichment
analysis identified CREB3L1/CrebA, which regulates COPII gene expression. CrebA
overexpression in C4 da neurons restores the dysregulation of COPII genes, GOP
synthesis, and PM supply. Chromatin immunoprecipitation (ChIP)-PCR revealed that
CrebA expression is regulated by CREB-binding protein (CBP), which is sequestered
by polyQ proteins. Furthermore, co-overexpression of CrebA and Rac1
synergistically restores the polyQ-induced dendrite pathology. Collectively, our
results suggest that GOPs impaired by polyQ proteins contribute to dendrite
pathology through the CBP-CrebA-COPII pathway.
PMID- 28700939
TI - Neogenin Recruitment of the WAVE Regulatory Complex to Ependymal and Radial
Progenitor Adherens Junctions Prevents Hydrocephalus.
AB - Denudation of the ependyma due to loss of cell adhesion mediated by cadherin
based adherens junctions is a common feature of perinatal hydrocephalus.
Junctional stability depends on the interaction between cadherins and the actin
cytoskeleton. However, the molecular mechanism responsible for recruiting the
actin nucleation machinery to the ependymal junction is unknown. Here, we reveal
that loss of the netrin/RGM receptor, Neogenin, leads to severe hydrocephalus. We
show that Neogenin plays a critical role in actin nucleation in the ependyma by
anchoring the WAVE regulatory complex (WRC) and Arp2/3 to the cadherin complex.
Blocking Neogenin binding to the Cyfip1/Abi WRC subunit results in actin
depolymerization, junctional collapse, and denudation of the postnatal
ventricular zone. In the embryonic cortex, this leads to loss of radial
progenitor adhesion, aberrant neuronal migration, and neuronal heterotopias.
Therefore, Neogenin-WRC interactions play a fundamental role in ensuring the
fidelity of the embryonic ventricular zone and maturing ependyma.
PMID- 28700941
TI - Probing Mammalian Cell Size Homeostasis by Channel-Assisted Cell Reshaping.
AB - Cell size homeostasis can be achieved by size checkpoints that couple cell size
to cell-cycle progression or by alternative mechanisms such as constant
extension. In mammalian cells, the existence of strict size checkpoints remains
controversial due to the technical limitations in determining cell size directly
and accurately. We developed a microfabricated channel system that linearizes
mammalian cell growth and facilitates cell size measurements. By tracking cell
length, while directly visualizing cell-cycle progression in rat basophilic
leukemia cells and RAW 264.7 macrophages, we examined the mechanisms of size
homeostasis and the existence of a size checkpoint at the G1/S transition. Our
analysis revealed a two-tier size homeostasis mechanism where a G1 "sizer" or
"adder" could operate, depending on the birth size of the cells.
PMID- 28700940
TI - In Vitro Modeling Using Ciliopathy-Patient-Derived Cells Reveals Distinct Cilia
Dysfunctions Caused by CEP290 Mutations.
AB - Mutations in CEP290, a transition zone protein in primary cilia, cause diverse
ciliopathies, including Leber congenital amaurosis (LCA) and Joubert-syndrome and
related disorders (JSRD). We examined cilia biogenesis and function in cells
derived from CEP290-LCA and CEP290-JSRD patients. CEP290 protein was reduced in
LCA fibroblasts with no detectable impact on cilia; however, optic cups derived
from induced pluripotent stem cells (iPSCs) of CEP290-LCA patients displayed less
developed photoreceptor cilia. Lack of CEP290 in JSRD fibroblasts resulted in
abnormal cilia and decreased ciliogenesis. We observed selectively reduced
localization of ADCY3 and ARL13B. Notably, Hedgehog signaling was augmented in
CEP290-JSRD because of enhanced ciliary transport of Smoothened and GPR161. These
results demonstrate a direct correlation between the extent of ciliogenesis
defects in fibroblasts and photoreceptors with phenotypic severity in JSRD and
LCA, respectively, and strengthen the role of CEP290 as a selective ciliary
gatekeeper for transport of signaling molecules in and out of the cilium.
PMID- 28700942
TI - A PML/Slit Axis Controls Physiological Cell Migration and Cancer Invasion in the
CNS.
AB - Cell migration through the brain parenchyma underpins neurogenesis and
glioblastoma (GBM) development. Since GBM cells and neuroblasts use the same
migratory routes, mechanisms underlying migration during neurogenesis and brain
cancer pathogenesis may be similar. Here, we identify a common pathway
controlling cell migration in normal and neoplastic cells in the CNS. The nuclear
scaffold protein promyelocytic leukemia (PML), a regulator of forebrain
development, promotes neural progenitor/stem cell (NPC) and neuroblast migration
in the adult mouse brain. The PML pro-migratory role is active also in
transformed mouse NPCs and in human primary GBM cells. In both normal and
neoplastic settings, PML controls cell migration via Polycomb repressive complex
2 (PRC2)-mediated repression of Slits, key regulators of axon guidance. Finally,
a PML/SLIT1 axis regulates sensitivity to the PML-targeting drug arsenic trioxide
in primary GBM cells. Taken together, these findings uncover a drug-targetable
molecular axis controlling cell migration in both normal and neoplastic cells.
PMID- 28700943
TI - A Role for Mitochondrial Translation in Promotion of Viability in K-Ras Mutant
Cells.
AB - Activating mutations in the KRAS oncogene are highly prevalent in tumors,
especially those of the colon, lung, and pancreas. To better understand the
genetic dependencies that K-Ras mutant cells rely upon for their growth, we
employed whole-genome CRISPR loss-of-function screens in two isogenic pairs of
cell lines. Since loss of essential genes is uniformly toxic in CRISPR-based
screens, we also developed a small hairpin RNA (shRNA) library targeting
essential genes. These approaches uncovered a large set of proteins whose loss
results in the selective reduction of K-Ras mutant cell growth. Pathway analysis
revealed that many of these genes function in the mitochondria. For validation,
we generated isogenic pairs of cell lines using CRISPR-based genome engineering,
which confirmed the dependency of K-Ras mutant cells on these mitochondrial
pathways. Finally, we found that mitochondrial inhibitors reduce the growth of K
Ras mutant tumors in vivo, aiding in the advancement of strategies to target K
Ras-driven malignancy.
PMID- 28700944
TI - Viral Activation of Heparanase Drives Pathogenesis of Herpes Simplex Virus-1.
AB - Herpes simplex virus-1 (HSV-1) causes lifelong recurrent pathologies without a
cure. How infection by HSV-1 triggers disease processes, especially in the immune
privileged avascular human cornea, remains a major unresolved puzzle. It has been
speculated that a cornea-resident molecule must tip the balance in favor of pro
inflammatory and pro-angiogenic conditions observed with herpetic, as well as non
herpetic, ailments of the cornea. Here, we demonstrate that heparanase (HPSE), a
host enzyme, is the molecular trigger for multiple pathologies associated with
HSV-1 infection. In human corneal epithelial cells, HSV-1 infection upregulates
HPSE in a manner dependent on HSV-1 infected cell protein 34.5. HPSE then
relocates to the nucleus to regulate cytokine production, inhibits wound closure,
enhances viral spread, and thus generates a toxic local environment. Overall, our
findings implicate activated HPSE as a driver of viral pathogenesis and call for
further attention to this host protein in infection and other inflammatory
disorders.
PMID- 28700945
TI - Reduced Circulating Insulin Enhances Insulin Sensitivity in Old Mice and Extends
Lifespan.
AB - The causal relationships between insulin levels, insulin resistance, and
longevity are not fully elucidated. Genetic downregulation of insulin/insulin
like growth factor 1 (Igf1) signaling components can extend invertebrate and
mammalian lifespan, but insulin resistance, a natural form of decreased insulin
signaling, is associated with greater risk of age-related disease in mammals. We
compared Ins2+/- mice to Ins2+/+ littermate controls, on a genetically stable
Ins1 null background. Proteomic and transcriptomic analyses of livers from 25
week-old mice suggested potential for healthier aging and altered insulin
sensitivity in Ins2+/- mice. Halving Ins2 lowered circulating insulin by 25%-34%
in aged female mice, without altering Igf1 or circulating Igf1. Remarkably,
decreased insulin led to lower fasting glucose and improved insulin sensitivity
in aged mice. Moreover, lowered insulin caused significant lifespan extension,
observed across two diverse diets. Our study indicates that elevated insulin
contributes to age-dependent insulin resistance and that limiting basal insulin
levels can extend lifespan.
PMID- 28700946
TI - SIFamide Translates Hunger Signals into Appetitive and Feeding Behavior in
Drosophila.
AB - Animal behavior is, on the one hand, controlled by neuronal circuits that
integrate external sensory stimuli and induce appropriate motor responses. On the
other hand, stimulus-evoked or internally generated behavior can be influenced by
motivational conditions, e.g., the metabolic state. Motivational states are
determined by physiological parameters whose homeostatic imbalances are signaled
to and processed within the brain, often mediated by modulatory peptides. Here,
we investigate the regulation of appetitive and feeding behavior in the fruit
fly, Drosophila melanogaster. We report that four neurons in the fly brain that
release SIFamide are integral elements of a complex neuropeptide network that
regulates feeding. We show that SIFamidergic cells integrate feeding stimulating
(orexigenic) and feeding suppressant (anorexigenic) signals to appropriately
sensitize sensory circuits, promote appetitive behavior, and enhance food intake.
Our study advances the cellular dissection of evolutionarily conserved signaling
pathways that convert peripheral metabolic signals into feeding-related behavior.
PMID- 28700947
TI - Acute Dietary Restriction Acts via TOR, PP2A, and Myc Signaling to Boost Innate
Immunity in Drosophila.
AB - Dietary restriction promotes health and longevity across taxa through mechanisms
that are largely unknown. Here, we show that acute yeast restriction
significantly improves the ability of adult female Drosophila melanogaster to
resist pathogenic bacterial infections through an immune pathway involving
downregulation of target of rapamycin (TOR) signaling, which stabilizes the
transcription factor Myc by increasing the steady-state level of its
phosphorylated forms through decreased activity of protein phosphatase 2A.
Upregulation of Myc through genetic and pharmacological means mimicked the
effects of yeast restriction in fully fed flies, identifying Myc as a pro-immune
molecule. Short-term dietary or pharmacological interventions that modulate TOR
PP2A-Myc signaling may provide an effective method to enhance immunity in
vulnerable human populations.
PMID- 28700948
TI - Peripartum Antibiotics Promote Gut Dysbiosis, Loss of Immune Tolerance, and
Inflammatory Bowel Disease in Genetically Prone Offspring.
AB - Factors affecting the developing neonatal gut microbiome and immune networks may
increase the risk of developing complex immune disorders such as inflammatory
bowel diseases (IBD). In particular, peripartum antibiotics have been suggested
as risk factors for human IBD, although direct evidence is lacking. Therefore, we
examined the temporal impact of the commonly used antibiotic cefoperazone on both
maternal and offspring microbiota when administered to dams during the peripartum
period in the IL-10-deficient murine colitis model. By rigorously controlling for
cage, gender, generational, and murine pathobiont confounders, we observed that
offspring from cefoperazone-exposed dams develop a persistent gut dysbiosis into
adulthood associated with skewing of the host immune system and increased
susceptibility to spontaneous and chemically dextran sodium sulfate (DSS)-induced
colitis. Thus, early life exposure to antibiotic-induced maternal dysbiosis
during a critical developmental window for gut microbial assemblage and immune
programming elicits a lasting impact of increased IBD risk on genetically
susceptible offspring.
PMID- 28700949
TI - Two Sets of Piwi Proteins Are Involved in Distinct sRNA Pathways Leading to
Elimination of Germline-Specific DNA.
AB - Piwi proteins and piRNAs protect eukaryotic germlines against the spread of
transposons. During development in the ciliate Paramecium, two Piwi-dependent
sRNA classes are involved in the elimination of transposons and transposon
derived DNA: scan RNAs (scnRNAs), associated with Ptiwi01 and Ptiwi09, and
iesRNAs, whose binding partners we now identify as Ptiwi10 and Ptiwi11. scnRNAs
derive from the maternal genome and initiate DNA elimination during development,
whereas iesRNAs continue DNA targeting until the removal process is complete.
Here, we show that scnRNAs and iesRNAs are processed by distinct Dicer-like
proteins and bind Piwi proteins in a mutually exclusive manner, suggesting
separate biogenesis pathways. We also demonstrate that the PTIWI10 gene is
transcribed from the developing nucleus and that its transcription depends on
prior DNA excision, suggesting a mechanism of gene expression control triggered
by the removal of short DNA segments interrupting the gene.
PMID- 28700950
TI - Transcriptional changes of rice in response to rice black-streaked dwarf virus.
AB - Rice black-streaked dwarf virus (RBSDV), a member of the genus Fijivirus in the
family Reoviridae, causes significant economic losses in rice production in China
and many other Asian countries. Although a great deal of effort has been made to
elucidate the interactions among the virus, insect vectors, host and
environmental conditions, few RBSDV proteins involved in pathogenesis have been
identified, and the biological basis of disease development in rice remains
largely unknown. Transcriptomic information associated with the disease
development in rice would be helpful to unravel the biological mechanism. To
determine how the rice transcriptome changes in response to RBSDV infection, we
carried out RNA-Seq to perform a genome-wide gene expression analysis of a
susceptible rice cultivar KTWYJ3. The transcriptomes of RBSDV-infected samples
were compared to those of RBSDV-free (healthy) at two time points (time points
are represented by group I and II). The results derived from the differential
expression analysis in RBSDV-infected libraries vs. healthy ones in group I
revealed that 102 out of a total of 281 significant differentially expressed
genes (DEGs) were up-regulated and 179 DEGs were down-regulated. Of the 2592
identified DEGs in group II, 1588 DEGs were up-regulated and 1004 DEGs were down
regulated. A total of 66 DEGs were commonly identified in both groups. Of these
66 DEGs, expression patterns for 36 DEGs were similar in both groups. Our
analysis demonstrated that some genes related to disease defense and stress
resistance were up-regulated while genes associated with chloroplast were down
regulated in response to RBSDV infection. In addition, some genes associated with
plant-height were differentially expressed. This result indicates those genes
might be involved in dwarf symptoms caused by RBSDV. Taken together, our results
provide a genome-wide transcriptome analysis for rice plants in response to RBSDV
infection which may contribute to the understanding of the regulatory mechanisms
involved in rice-RBSDV interaction and the biological basis of rice black
streaked dwarf disease development in rice.
PMID- 28700951
TI - Diabetic retinopathy, metabolic memory and epigenetic modifications.
AB - Retinopathy, a sight-threatening disease, remains one of the most feared
complications of diabetes. Although hyperglycemia is the main initiator,
progression of diabetic retinopathy continues even after re-institution of normal
glycemic control in diabetic patients, and the deleterious effects of prior
hyperglycemic insult depend on the duration and the severity of this insult,
suggesting a 'metabolic memory' phenomenon. Metabolic memory phenomenon is
successfully duplicated in the experimental models of diabetic retinopathy.
Hyperglycemia, in addition to initiating many other biochemical and functional
abnormalities and altering expression of genes associated with them, also
increases oxidative stress. Increased production of cytosolic reactive oxygen
species dysfunctions the mitochondria, and a compromised antioxidant defense
system becomes overwhelmed to neutralize free radicals. With the duration of
diabetes extending, mitochondrial DNA (mtDNA) is also damaged, and transcription
of mtDNA-encoded genes, important for function of the electron transport chain,
is compromised. This fuels into a 'self-propagating' vicious cycle of free
radicals, and retinopathy continues to progress. Hyperglycemic insult also
affects the enzymatic machinery responsible for epigenetic modifications; these
modifications alter gene expression without affecting the DNA sequence. Histones
and/or DNA modifications of many enzymes, important in mitochondrial homeostasis,
affect their activities and disturb mitochondrial homeostasis. Experimental
models have shown that these epigenetic modifications have potential to halt only
if normal glycemia is maintained from the day of induction of diabetes
(streptozotocin) in rats, but if hyperglycemia is allowed to proceed even for
couple months before initiation of normal glycemia, these epigenetic modification
resist reversal. Supplementation of a therapy targeted to prevent increased
oxidative stress or epigenetic modifications, during the normal glucose phase,
which has followed high glucose insult, however, helps ameliorate these
abnormalities and prevents the progression of diabetic retinopathy. Thus, without
undermining the importance of tight glycemic control for a diabetic patient,
supplementation of their 'best possible' glycemic control with such targeted
therapies has potential to retard further progression of this blinding disease.
PMID- 28700952
TI - Nicotine facilitates nicotinic acetylcholine receptor targeting to mitochondria
but makes them less susceptible to selective ligands.
AB - Several nicotinic acetylcholine receptor (nAChR) subtypes are expressed in
mitochondria to regulate the internal pathway of apoptosis in ion channel
independent manner. However, the mechanisms of nAChR activation in mitochondria
and targeting to mitochondria are still unknown. Nicotine has been shown to favor
nAChR pentamer assembly, folding, and maturation on the way of biosynthesis. The
idea of the present work was to determine whether nicotine affects the content,
glycosylation, and function of mitochondrial nAChRs. Experiments were performed
in isolated liver mitochondria from mice, that either consumed or not nicotine
with the drinking water (200MUL/L) for 7days. Mitochondria detergent lysates were
studied by sandwich or lectin ELISA for the presence and carbohydrate composition
of different nAChR subunits. Intact mitochondria were examined by flow cytometry
for the binding of fluorescently labeled alpha-cobratoxin and were tested in
functional assay of cytochrome c release under the effect of either Ca2+ or
wortmannin in the presence or absence of nAChR-selective ligands, including PNU
282987 (1nM), dihydro-beta-erythroidine (DhbetaE, 1MUM), PNU-120596 (0.3, 3, or
10MUM) and desformylflustrabromine hydrochloride (dFBr, 0.001, 0.3, or 1MUM). It
was found that nicotine consumption increased the ratio of mitochondrial vs non
mitochondrial nAChRs in the liver, enhanced fucosylation of mitochondrial nAChRs,
but prevented the binding of alpha-cobratoxin and the cytochrome c release
attenuating effects of nAChR-specific agonists, antagonists, or positive
allosteric modulators. It is concluded that nicotine consumption in vivo favors
nAChR glycosylation and trafficking to mitochondria but makes them less
susceptible to the effects of specific ligands.
PMID- 28700953
TI - Comparative assessment of local tolerance of alcohols commonly used in alcohol
based hand rubs for hand hygiene.
AB - Hand hygiene plays a key role in nosocomial infection prevention. To achieve
users' adherence, products' dermal tolerance is essential. We aimed at making a
comparative assessment of skin irritation and phototoxicity of the 3 alcohols
commonly used in alcohol-based hand rubs (Ethanol, Propan-2-ol, Propan-1-ol) at
60, 70, 80 or 85% w/w in water or with co-formulates (hydrating, emollient and
skin protective agents). In vitro validated OECD methods 439 and 432 were used.
For irritation, EpiSkinTM Small Model was the chosen Reconstructed Human
Epidermis (RhE). For phototoxicity, co-formulates alone or in mixture with and
without alcohol were tested using BALB/c 3T3 cell cultures. Whilst Ethanol and
Propan-2-ol could not be differentiated and displayed good skin tolerance
profiles, Propan-1-ol based products lead to significant viability impairments of
RhE at 60, 70 or 80% and at 60% in the presence of co-formulates. However, these
results could not be reproduced in another RhE model. Taking also into account
bibliographic data on Propan-1-ol, this suggests that our results are probably
related to a lack of specificity of the used RhE. Therefore, it can be relevant
in case of significant results to use two different RhE models before performing
any classification and/or performing any complementary tests.
PMID- 28700954
TI - Cognitive and motor reaction times in obstructive sleep apnea syndrome: A study
based on computerized measures.
AB - Obstructive Sleep Apnea Syndrome (OSAS) is mainly associated with executive
dysfunction. Although delayed reaction times (RTs) in patients with OSAS have
been reported, sensitivity of processing speed has not been adequately assessed.
This study suggests sensitive and reliable measures to clarify whether different
components of information processing speed, i.e. cognitive and motor responses,
are equally impaired in OSAS. Thirty-three patients with OSAS were compared with
thirty healthy controls. The MoCA test was administered to assess participants'
global neuropsychological profile. Cognitive and motor reaction times were
measured using a detector panel which allows to distinguish between stimulus
encoding, decision processing, and selection of the appropriate motor response.
Logistic regression models highlighted both MoCA test and motor RTs as the best
predictors differentiating patients from healthy participants. Results support
the hypothesis of a slight decline in the cognitive profile of patients with OSAS
and identify significant slowing down in the motor component of responses. It
could be hypothesized that slower motor responsiveness is the cause of the global
cognitive profile of these patients. With aging, motor movements and RTs usually
become impaired and hypoxia might accelerate the aging process by compromising
first of all the motor component of RTs.
PMID- 28700955
TI - Liver specific gene immunotherapies resolve immune suppressive ectopic lymphoid
structures of liver metastases and prolong survival.
AB - : The ability to generate potent immunotherapies locally and transiently for the
treatment of cancers is a promising strategy to improve efficacy and decrease off
target toxicities. Here, we explored an alternative approach for the delivery of
immunotherapeutic agents, in which we deliver the pDNA of an engineered PD-L1
trap and/or CXCL12 trap to the nucleus of liver hepatocytes via a lipid calcium
phosphate nanoparticle. This strategy greatly increased the concentrations of
immunotherapeutic agents in the local tissue, allowing the therapy to inhibit the
accumulation of immune suppressive cells and liver metastasis. Furthermore, we
find that the lipid calcium phosphate nanoparticles containing the pCXCL12 trap
resolved the formation of immune suppressive ectopic lymphoid structures, while
the pPD-L1 trap promoted T-cell survival and migration into the liver following
vaccination against tumor antigens (>180% increase in survival). This approach
showed superior efficacy in the treatment of the liver metastasis compared to
free protein immunotherapies. This strategy should be considered as an approach
to support liver metastasis therapies as well as for future research interested
in manipulating the chemokine/cytokine immune factors within the liver.
SIGNIFICANCE: Our approach results in transient liver specific expression of gene
immunotherapies with improved efficacy and reduced off-target toxicities over
traditional systemically administered immunotherapies. This approach would allow
clinicians to manipulate the liver and immune microenvironment to resist cancer
invasion, improve organ health, and prolong patient survival.
PMID- 28700956
TI - Sludge conditioning using the composite of a bioflocculant and PAC for
enhancement in dewaterability.
AB - This study investigated the production of a bioflocculant by using rice stover
and its potential in sludge dewatering. Production of the bioflocculant was
positively associated with cell growth and highest value of 2.37 g L-1 was
obtained with main backbone of polysaccharides. The bioflocculant showed good
performances in sludge dewatering, after conditioned by this bioflocculant, dry
solids (DS) and specific resistance to filtration (SRF) of typical wastewater
activated sludge reached 19.3% and 4.8 * 1012 m kg-1, respectively, which were
much better than the ones obtained with chemical flocculants. Sludge dewatering
was further improved when the bioflocculant and polyaluminum chloride (PAC) were
used simultaneously, and the optimized conditioning process by the composite was
bioflocculant of 10.5 g kg-1, PAC of 19.4 g kg-1, and pH of 8.1. Under this
optimal condition, DS and SRF of the sludge appeared as 24.1% and 3.0 * 1012 m kg
1, respectively.
PMID- 28700957
TI - A protective role of Heme-regulated eIF2alpha kinase in cadmium-induced liver and
kidney injuries.
AB - A number of studies have reported that cadmium (Cd) can incur liver and kidney
injuries. The recruitment and activation of leukocytes have been demonstrated to
be involved in Cd-induced biological effects. Ironically, activated leukocytes
and secreted cytokines are also reported to be required for the later recovery of
the damaged tissues. Yet, the mechanisms driving the production of leukocytes
have not been fully elucidated. Heme-regulated eIF2alpha kinase (HRI) is
essential for translational regulation and stressed erythropoiesis in iron
deficiency. Meanwhile, HRI is important in the maturation and function of
macrophages, indicating that HRI might be indispensable for the development and
function of other myeloid lineages. Apart from macrophages, whether HRI regulates
the production of leukocytes and further affects Cd-induced tissue injuries is
still elusive. In this study, we aimed to elucidate the role of HRI in liver and
kidney injuries and the associated mechanisms upon Cd exposure. We found that Cd
exposed mice showed impaired production of leukocytes and developed morphological
disorders in liver and kidney. Furthermore, Hri null mice exhibited a reduced
number of monocytes and neutrophils and compromised cytokine production, relative
to wild-type mice. Absence of Hri also exacerbated the impairments of liver and
kidney upon Cd treatment. Together, these results highlighted a crucial role of
HRI in protecting liver and kidney against Cd-induced injuries through inducing
the development of monocytes and neutrophils. Our results further extended the
understanding of HRI on the regulation of non-erythroid lineages and might
provide new aspects for preventing and treating Cd-induced detrimental effects.
PMID- 28700958
TI - Tolerance to heavy metals in filamentous fungi isolated from contaminated mining
soils in the Zanjan Province, Iran.
AB - In the present study the population of fungi inhabiting metal contaminated soil
samples from lead-zinc mining area was investigated, and their tolerance and
biosorption capacity towards Cd, Pb, Zn and Cu were evaluated. Fungal species,
including Acremonium persicinum, Penicillium simplicissimum, Seimatosporium
pistaciae, Trichoderma harzianum, Alternaria chlamydosporigena and Fusarium
verticillioides were isolated. Fungal tolerance was determined by measuring of
the "Minimum Inhibitory Concentration", after exposure to increasing
concentrations of heavy metal chlorides. Among the test fungi, Trichoderma
harzianum was the most tolerant against Cd, Pb and Cu. The Heavy metal content in
the fungal biomass was quantified after combustion. The calculated total sorption
of heavy metals showed that Acremonium persicinum and Penicillium simplicissimum
had the highest accumulation of Zn and Cu, respectively. The data presented in
this study should help to use the accumulation potential of some of those fungal
species examined for bioremediation of contaminated soils.
PMID- 28700959
TI - Relationship between physical activity practice and metabolic profile of
postmenopausal women under treatment with aromatase inhibitors for breast cancer.
AB - OBJECTIVE: To analyze the relationship between physical activity practice and
metabolic profile of postmenopausal women under treatment with aromatase
inhibitors (AIs) for the treatment of breast cancer. STUDY DESIGN: Cross
sectional study, conducted with 101 postmenopausal women (aged 50-80 years). The
sample was divided into two groups; group without cancer (GW; n=65) and breast
cancer group treated with AIs (GC; n=36). Physical activity (PA) was evaluated by
questionnaire. Correlations between physical activity and metabolic variables
were made by Pearson's correlation coefficient and the magnitude of these
relationships by linear regression. RESULTS: In GW, there were observed
significant inverse correlations between physical activity and VLDL cholesterol
(beta=-0.036; 95% CI=-0.068; -0.004); triglycerides (beta=-0.036; 95% CI=-0.015;
0.002); glycose (beta=-0.029; 95% CI=-0.047; -0.012); and C-reactive protein
(beta=-0.44; 95% CI=-0.085; -0.003). However, for women under treatment of AIs
there was no relationship between physical activity and metabolic variables.
CONCLUSION: The amount of physical activity practice is inversely related to
lipid profile, glucose and C-reactive protein in women without breast cancer.
This relation was not observed in the cancer survivors, suggesting that the use
of aromatase inhibitors could influence or low intensity of physical activity.
PMID- 28700960
TI - Relationships between affiliative social behavior and hair cortisol
concentrations in semi-free ranging rhesus monkeys.
AB - Sociality is a fundamental aspect of human behavior and health. One benefit of
affiliative social relationships is reduced short-term levels of glucocorticoids
(GCs), which are indicative of physiological stress. Less is known, however,
about chronic GC production in relation to affiliative social behavior. To
address this issue, we studied a semi-free ranging troop of rhesus macaques
(Macaca mulatta) and collected hair samples to measure hair cortisol
concentrations (HCCs), as a measure of chronic GC production, during routine
biannual exams. We collected social behavior (both aggressive and affiliative)
and hair samples for 32 adult female rhesus macaques over one year (Experiment
1). Our results indicated that adult females who initiated higher levels of
social affiliation had significantly lower levels of HCCs. Neither the initiation
nor the receipt of aggression were significantly related to HCCs in this study.
In a second experiment we studied 28 mother-infant dyads for the first 90days
postpartum to examine mother-infant facial interactions (i.e. mutual gazing). We
analyzed HCCs during weaning approximately one year later, which is a major
transitional period. We found that infants that engaged in higher levels of
mutual gazing in the first 90days postpartum had significantly lower levels of
HCCs during weaning. Finally, we studied 17 infant rhesus macaques (13 males) to
examine whether social behavior (such as play) in the first five months of life
correlated with infant HCCs over those months (Experiment 3). We found that
infant males that engaged in more social play had significantly lower levels of
HCCs. By relying on an animal model, our study shows that affiliative social
traits are associated with lower long-term GC production. Future research should
address the complex interactions between social behavior, chronic GC production,
and mental and physical health.
PMID- 28700961
TI - Biotin-Pt (IV)-indomethacin hybrid: A targeting anticancer prodrug providing
enhanced cancer cellular uptake and reversing cisplatin resistance.
AB - A Pt(IV) prodrug (2) composed of cancer-targeting biotin and nonsteroidal anti
inflammatory drug indomethacin in the axial positions of the six-coordinated
octahedral geometry derived from cisplatin was developed, which could be highly
accumulated in cancer cells more than normal ones and activated by endogenous
reducing molecules to release cisplatin and indomethacin moieties simultaneously
to inhibit tumor progression synergistically. In vitro assays revealed that 2
exhibited significantly selective inhibition to the tested cancer cell lines and
sensitivity to cisplatin resistant cancer cells. Moreover, 2 presented
cyclooxygenases inhibition properties to reduce tumor-associated inflammation,
reduced the invasiveness of the highly aggressive PC-3 cells, and disrupted
capillary-like tube formation in EA.hy926 cells. In all, this study offers a new
strategy to enhance sensitivity and reduce toxicity of cisplatin.
PMID- 28700962
TI - Studies on the structural changes during curing of epoxy and its blend with CTBN.
AB - Cashew nut shell liquid (CNSL), an agricultural renewable resource material,
produces natural phenolic distillates such as cardanol. Cardanol condenses with
formaldehyde at the ortho- and para-position of the phenolic ring under acidic or
alkaline condition to yield a series of polymers of novolac- or resol-type
phenolic resins. These phenolic resins may further be modified by epoxidation
with epichlorohydrin to duplicate the performance of such phenolic-type novolacs
(CFN). The structural changes during curing of blend samples of epoxy and
carboxyl terminated poly (butadiene-co-acrylonitrile) (CTBN) were studies by
Fourier-transform infrared (FTIR) spectrophotometer. The epoxy samples were
synthesized by biomass material, cardanol. Blend sample was prepared by physical
mixing of CTBN ranging between 0 and 20weightpercent CTBN liquid rubber into
cardanol-based epoxidized novolac (CEN) resin. The FTIR spectrum of uncured blend
sample clearly indicated that there appeared a band in the region of 3200-3500cm
1 which might be due to the presence of phenolic hydroxyl group and OH group of
the opened epoxide. Pure epoxy resin showed peaks near 856cm-1 which might be due
to oxirane functionality of the epoxidized novolac resin. Both epoxy and its
blend sample was cured with polyamine. The cure temperature of CEN resin was
found to be decreased by the incorporation of CTBN. The decomposition behavior
was also studied by thermogravimetric analyzer (TGA). Two-step decomposition
behavior was observed in both epoxy and its blend samples.
PMID- 28700963
TI - Application of DIP-STRs to sexual/physical assault investigations: Eight case
reports.
AB - DIP-STRs are compound markers formed by a deletion/insertion polymorphism linked
to a microsatellite. They enable the deconvolution of unbalanced DNA mixtures
from two individuals, up to 1000 fold excess of one contributor. In practice,
this novel tool allows to test for the presence of a DNA of interest in traces
appearing not useful because of the masking effect of the major DNA contributor.
Thus far two sets of DIP-STRs have been published: the first set was described as
proof-of-principle, while the second set was specifically developed for forensic
applications. Here, we report on the first use of these markers in casework to
show advantages and limitations in real examples. Traces, suggestive of
containing unbalanced DNA mixtures (beyond standard STR mixture resolution), were
selected from eight cases submitted to the Forensic Genetics Unit of the
University Center of Legal Medicine of Lausanne-Geneva. Using 18 validated DIP
STRs, two to ten markers were selected for each case. A minor DNA contributor -
undetected using conventional STRs - was detected for the trace samples of six
cases. DIP-STR results contributed to each case, either by complementing Y-STRs
results or by producing novel investigative leads. This was especially true with
same sex unbalanced DNA mixtures, female minor/male major unbalanced DNA mixtures
or when the source of the DNA mixture was said to come either from the suspect
and the female complainant or from his brother and the female complainant.
Interestingly, these markers were found to be more sensitive and specific than
previously known. Positive results were obtained at 16,000-fold excess of major
DNA using few picograms of input DNA, as well as from traces collected several
months after the alleged offence. Likelihood ratios assigned to measure the
strength of DIP-STRs' DNA evidence were modest (10), when accounted by only two
DIP-STRs, and high (106) when determined by six markers. In some cases the
detection of extra alleles from additional minor DNA contributors or because of
extremely unbalanced DNA ratios, limited the interpretation of the results. In
conclusion, the DIP-STRs often provide additional value to the analysis of traces
that cannot be exploited by the use of standard methods.
PMID- 28700964
TI - Clinical and laboratory predictors of Infectious Complications in patients after
Out-of-Hospital Cardiac Arrest.
AB - PURPOSE: Identification of clinical and laboratory predictors related to
Infectious Complications (ICs) in patients after Out-of-Hospital Cardiac Arrest
(OHCA). METHODS: Patients, aged >18, after an OHCA between 9/2013 and 11/2015,
surviving >24h, were studied. RESULTS: Study group consisted of 42 patients (mean
age 63.4years, 88.1% men). Forty percent of patients had IC; lower respiratory
tract infections were most common (87.5% of cases). ICs were more common in
patients receiving Targeted Temperature Management (50% vs. 10%; p=0.032).
Antibiotics were used in 85.7% of patients. The mean time to therapy initiation
was 9.6 (SD 7.1) hours after admission. The mean course of treatment was 9.0 (SD
6.2) days. Fifty-three percent of patients receiving early antibiotic treatment
didn't have IC. Initial antibiotic therapy was changed more often in patients
with IC (75% vs. 38.9%; p=0.045). C-Reactive Protein, Procalcitonin, Troponin and
White Blood Cell count values were higher in patients with IC. CONCLUSION: Early
initiated antibiotic treatment is overused in patients after OHCA. This practice
is associated with necessitating antibiotic change in the majority of patients
with IC. Assessment of clinical and laboratory parameters in the first days after
OHCA increases the likelihood of appropriate ATB therapy.
PMID- 28700965
TI - Inhibitory effects of ASP6537, a selective cyclooxygenase-1 inhibitor, on
thrombosis and neointima formation in rats.
AB - INTRODUCTION: Percutaneous coronary interventions (PCIs), such as balloon
angioplasty and stent placement, are effective in the treatment of coronary
artery disease. PCI has drawbacks, however, including acute thrombosis after the
procedure and restenosis of the vascular lumen due to abnormal neointimal
hyperplasia. ASP6537 is a selective COX-1 inhibitor that has been investigated as
a possible candidate for clinical development as an antiplatelet agent. In the
present study, we evaluated the in vivo antithrombotic effect of ASP6537 and its
effect on neointima formation after balloon angioplasty. MATERIAL AND METHODS:
The antithrombotic effect of ASP6537 was examined using an arteriovenous shunt
thrombosis model in rats while the effect of ASP6537 on neointima formation was
evaluated in a rat carotid arterial balloon angioplasty model. RESULTS: In the
thrombosis study, ASP6537 dose-dependently decreased the protein content of the
thrombus, while no prolongation of template bleeding time was observed. In the
neointima study, ASP6537 reduced neointima formation. CONCLUSIONS: ASP6537 may be
a promising agent for the prevention of acute thrombosis and restenosis after PCI
in place of aspirin.
PMID- 28700966
TI - Utility of surveillance MRI in women with a personal history of breast cancer.
AB - PURPOSE: To determine the utility and rate of biopsy in women with a positive
history of breast cancer screened with MRI. METHODS: Retrospective review of 491
breast MRI screening examinations in women with a personal history of breast
cancer. RESULTS: In total, 107 biopsies were performed, an average of 0.09
biopsies per person year. The positive predictive value for biopsies prompted by
MRI findings was 0.24 (95% C.I. 0.10-0.38). Eight of the nine subsequent cancers
were initially identified on screening MRI alone. CONCLUSION: Surveillance MRI in
breast cancer survivors may increase detection of subsequent cancers while
increasing rate of biopsy.
PMID- 28700967
TI - Eosinophilic granuloma at the cerebellopontine angle in an adult; a rare case
report and literature review.
AB - INTRODUCTION: Langerhans cell histiocytosis (LCH) is a rare immunologic disorder,
identified by immature proliferation of histiocytes which may present as systemic
or focal lesions. Eosinophilic granuloma (EG) is localized from of LCH mainly
involving bones such as skull, femur, spine, ribs, mandible and pelvis. Cerebello
pontine (CP) angle is a rare anatomic location for involvement by EG.
PRESENTATION OF CASE: A 32 year old man was being evaluated in our neuro-oncology
clinic due to diplopia since 4 months ago. On physical examination he had left
sided abducens paresis, hyposthesia over left half of his face and a decreased
corneal reflex on left side. A magnetic resonance imaging (MRI) study revealed a
lesion at left CP angle measuring 30*25*25mm in size which was isointense in T1,
hypointense on T2 with homogenous enhancement in post-contrast study. A standard
retrosigmoid approach was carried out for resection of this lesion. Pathology
report of the frozen section depicted infiltration of eosinophils and large mono
nuclear cells. The infiltrative nature of the lesion encouraged us not to attempt
further resection. Permanent pathology report was in favor of EG. Patient was
referred to an oncology clinic for proceeding with the steroid therapy.
DISCUSSION: To the best of authors' knowledge, this is the first report of EG at
CP angle in an adult, in the literature. Infiltration of eosinophils and
positivity for CD1a and S-100 renders the diagnosis unmistakable. CONCLUSION:
When the diagnosis is suggestive of EG, incompletely excised lesions can be
further managed by steroid therapy.
PMID- 28700968
TI - Retrocecal hernia preoperatively diagnosed by computed tomography: A case report.
AB - INTRODUCTION: Retrocecal hernia is a rare type of pericecal hernia. Because it is
difficult to diagnose preoperatively, it is often treated with emergency
operation. CASE PRESENTATION: An 83-year-old male patient experienced sudden
abdominal pain. Marked small bowel dilatation and intestinal obstruction were
detected by abdominal computed tomography (CT). An enhanced CT scan also revealed
a trapped cluster of small bowel loops behind the cecum and ascending colon. We
preoperatively diagnosed small bowel ileus as a result of retrocecal hernia.
After conservative therapy with a long intestinal tube, an emergency operation
was performed. During the surgery, a portion of the ileum was found to be
incarcerated in the retrocecal fossa. Intestinal resection was not necessary
because the incarcerated ileum appeared viable, and the orifice to the hernia was
opened. The patient was discharged without postoperative complications.
DISCUSSION: The diagnosis of retrocecal hernia can often be confirmed
intraoperatively. This disease is identified based on a minimal error in rotation
with incarceration behind the cecum during the final phase of descent and
fixation of the right colon or failure of cecal and retroperitoneal fixation.
Early preoperative diagnosis is important to prevent intestinal ischemia,
necrosis, and perforation and to reduce resection rates. CONCLUSION: Early
preoperative diagnosis is important to avoid resection of the small intestine. CT
scans are useful for preoperative diagnosis in case of retrocecal hernia.
PMID- 28700969
TI - Solubilization of poorly water-soluble compounds using amphiphilic phospholipid
polymers with different molecular architectures.
AB - To achieve stable and effective solubilization of poorly water-soluble bioactive
compounds, water-soluble and amphiphilic polymers composed of hydrophilic 2
methacryloyloxyethyl phosphorylcholine (MPC) units and hydrophobic n-butyl
methacrylate (BMA) units were prepared. MPC polymers having different molecular
architectures, such as random-type monomer unit sequences and block-type
sequences, formed polymer aggregates when they were dissolved in aqueous media.
The structure of the random-type polymer aggregate was loose and flexible. On the
other hand, the block-type polymer formed polymeric micelles, which were composed
of very stable hydrophobic poly(BMA) cores and hydrophilic poly(MPC) shells. The
solubilization of a poorly water-soluble bioactive compound, paclitaxel (PTX), in
the polymer aggregates was observed, however, solubilizing efficiency and
stability were strongly depended on the polymer architecture; in other words, PTX
stayed in the poly(BMA) core of the polymer micelle formed by the block-type
polymer even when plasma protein was present in the aqueous medium. On the other
hand, when the random-type polymer was used, PTX was transferred from the polymer
aggregate to the protein. We conclude that water-soluble and amphiphilic MPC
polymers are good candidates as solubilizers for poorly water-soluble bioactive
compounds.
PMID- 28700970
TI - Identification of impurities in macrolides by liquid chromatography-mass
spectrometric detection and prediction of retention times of impurities by
constructing quantitative structure-retention relationship (QSRR).
AB - Macrolides are multicomponent drugs whose impurity control is always a challenge
demanding analysis method with good sensitivity and selectivity. Three separate,
sensitive, accurate liquid chromatography tandem mass spectrometry methods (LC
MS) were developed for the measurement of three 16-membered ring macrolides
(josamycin, josamycin propionate and midecamycin acetate) and related substances
in commercial samples. The characteristics of impurities in macrolides were
summarized as useful guidance for the impurity analysis of this class of drugs.
For each drug, a large number of unknown components have been detected with the
high-sensitive MS detector and possible structures of the majority of them were
postulated based on the summarized fragmentation rules of 16-membered ring
macrolides. A QSRR model was constructed by multilinear regression to predict the
retention times of identified impurities which were not detected by the LC-MS
methods, without obtaining their reference standards. Satisfactory performance
was obtained during leave-one-out cross-validation with a predictive ability (Q2)
of 0.95. The generalisation ability of the model was further confirmed by an
average error of 2.3% in external prediction. The best QSRR model, based on eight
molecular descriptors, exhibited a promising predictive performance and
robustness.
PMID- 28700971
TI - Comparative study on the anticancer activities and binding properties of a hetero
metal binuclear complex [Co(dipic)2Ni(OH2)5].2H2O (dipic=dipicolinate) with two
carrier proteins.
AB - Recognizing of binding mechanisms between drugs and carrier proteins is basic for
us to understand the pharmacokinetics and pharmacodynamics of them. In this
research, the anticancer activities of a binuclear complex
[Co(dipic)2Ni(OH2)5].2H2O (dipic=dipicolinate) against MDA-MB-231 cell lines were
studied. Results of MTT assay and flow cytometry analysis revealed that above
complex can induce the cytotoxicity and the apoptosis in breast cancer cell
lines. So, this complex was selected to investigate its binding to human serum
albumin (HSA) and bovine beta-lactoglobulin (betaLG) by spectroscopic methods (UV
visible, fluorescence and FT-IR) along with molecular docking technique. The
fluorescence data showed Co-Ni complex quench the fluorescence of both proteins
by a static quenching mechanism and HSA has stronger binding affinity toward Co
Ni complex than betaLG. The binding constant (Kb), number of binding sites (n)
and thermodynamic parameters were calculated and showed that the Co-Ni complex
binds to protein (HSA and betaLG) through hydrogen bonding and van der Waals
forces with one binding site. The results of UV-visible measurements indicated
that the binding of above complex to HSA and betaLG may induce conformational and
micro-environmental changes of studied proteins. Protein-ligand docking analysis
confirmed that the Co-Ni complex binds to residues located in the subdomain IIA
of HSA and site II of betaLG.
PMID- 28700972
TI - Evaluating the use of in-situ turbidity measurements to quantify fluvial sediment
and phosphorus concentrations and fluxes in agricultural streams.
AB - Accurate quantification of suspended sediments (SS) and particulate phosphorus
(PP) concentrations and loads is complex due to episodic delivery associated with
storms and management activities often missed by infrequent sampling. Surrogate
measurements such as turbidity can improve understanding of pollutant behaviour,
providing calibrations can be made cost-effectively and with quantified
uncertainties. Here, we compared fortnightly and storm intensive water quality
sampling with semi-continuous turbidity monitoring calibrated against spot
samples as three potential methods for determining SS and PP concentrations and
loads in an agricultural catchment over two-years. In the second year of sampling
we evaluated the transferability of turbidity calibration relationships to an
adjacent catchment with similar soils and land cover. When data from nine storm
events were pooled, both SS and PP concentrations (all in log space) were better
related to turbidity than they were to discharge. Developing separate calibration
relationship for the rising and falling limbs of the hydrograph provided further
improvement. However, the ability to transfer calibrations between adjacent
catchments was not evident as the relationships of both SS and PP with turbidity
differed both in gradient and intercept on the rising limb of the hydrograph
between the two catchments. We conclude that the reduced uncertainty in load
estimation derived from the use of turbidity as a proxy for specific water
quality parameters in long-term regulatory monitoring programmes, must be
considered alongside the increased capital and maintenance costs of turbidity
equipment, potentially noisy turbidity data and the need for site-specific
prolonged storm calibration periods.
PMID- 28700973
TI - Fit-for-purpose wastewater treatment: Testing to implementation of decision
support tool (II).
AB - This paper is the second in a series of two papers. In Paper I, a decision
support tool (DST), FitWater, was developed for evaluating the potential of
wastewater treatment (WWT) trains for various water reuse applications. In the
present paper, the proposed DST has been tested and implemented. FitWater has
been tested with several existing WWT plants in Canada and the USA, demonstrating
FitWater's effectiveness in estimating life cycle cost (LCC), health risk, and
energy use. FitWater has also been implemented in a newly planned neighbourhood
in the Okanagan Valley (BC, Canada) by developing 12 alternative WWT trains for
water reuse in lawn and public parks irrigation. The results show that FitWater
can effectively rank WWT train alternatives based on LCC, health risk, amount of
reclaimed water, energy use, and carbon emissions. Moreover, functions have been
developed for the variation of unit annualized LCC and energy intensity per unit
log removal of microorganisms in different treatment technologies with varying
plant capacities. The functions have power relations, showing the economies of
scale. FitWater can be applied to identify a cost-effective, risk-acceptable, and
energy efficient wastewater treatment train with a plant capacity of 500m3/day or
more. Furthermore, FitWater can be used to assess potential economic impacts of
developing microbiologically stringent effluent standards. The capability of
FitWater can be enhanced by including physio-chemical quality of wastewater,
additional treatment technologies, and carbon emissions from wastewater
decomposition processes.
PMID- 28700974
TI - Mechanism of berberine-mediated fluconazole-susceptibility enhancement in
clinical fluconazole-resistant Candida tropicalis isolates.
AB - BACKGROUND: Candida tropicalis was one of the most common non-albicans Candida
(NACA) species creating relatively high morbidity and mortality. We previously
demonstrated that the antifungal effect of BBR in combination with FLC might be
attributed to reactive oxygen species production, ergosterol content and efflux
pump levels in a clinical C. tropicalis isolate. METHODS: we employed thirteen
clinical C. tropicalis isolates as well as four standard reference strains to
evaluate the antifungal activity of BBR in combination with FLC under planktonic
and biofilm states by analyzing the mRNA expressions of ERG11, CDR1 and MDR1 by
qRT-PCR. RESULTS: The susceptibility tests showed that BBR in combination with
FLC produced a FICI range of 0.13-1 under planktonic state and 0.25-1 under
biofilm state in the seventeen strains. The mRNA expressions of ERG11, CDR1 and
MDR1 were upregulated 1.43-2.10 and 1.47-4.42 fold in the case of BBR/FLC used
alone compared with the control. The combined usage of BBR plus FLC resulted in a
decrease of 2.84- (p<0.01) and 2.39-fold (p<0.05) in the expression of ERG11
mRNA, 2.98- (p<0.05) and 3.06-fold (p<0.05) in the expression of CDR1 mRNA, 1.41-
and 4.33-fold in the expression of MDR1 mRNA compared with the BBR/FLC used
alone. CONCLUSION: The synergism of BBR with FLC might be relevant with the
inhibitions on the mRNA expressions of ERG11 and efflux pumps.
PMID- 28700975
TI - Astilbin decreases proliferation and improves differentiation in HaCaT
keratinocytes.
AB - Psoriasis is a common chronic dermatosis characterized by keratinocyte
hyperproliferation accompanied by inflammatory reactions. Pathological changes
upset the balance between keratinocyte proliferation, differentiation, and death
in psoriatic lesions, suggesting that molecules with topical anti-inflammatory,
anti-proliferation and anti-angiogenesis abilities may be useful for its
treatment. The flavonoid astilbin is the major active component extracted from
the rhizome of Smilax glabra, which has been widely used in China to treat
inflammatory and autoimmune diseases. Here, we investigate the potential of
astilbin as a treatment for psoriasis. We reveal that astilbin inhibits the
growth of HaCaT keratinocytes. Detailed study shows that astilbin leads to S
phase arrest of the cell cycle by induction of p53 and p21 and activated-AMPK.
Additionally, astilbin induced keratinocyte differentiation correlated with
suppression of keratin 5 (KRT5) and KRT14 proteins (the markers of epidermal
basal layer) and induction KRT1 and KRT10 proteins (occurring in the upper
layers). Moreover, astilbin regulates the expression of VEGF in human HaCaT
keratinocytes. These results suggest that astilbin may be a promising agent for
psoriasis treatment.
PMID- 28700976
TI - The protective effect of coptisine on experimental atherosclerosis ApoE-/- mice
is mediated by MAPK/NF-kappaB-dependent pathway.
AB - Coptisine is one of main bioactive compounds extracted from the traditional
Chinese herbal medicine Rhizoma Coptidis. It is reported that coptisine can
attenuate obesity-related inflammation and oxidant damage in Syrian golden
hamsters. Therefore,coptisine may exhibit beneficial effects for the treatment of
atherosclerosis (AS) due to its hypolipidemic and anti-inflammation activities.
The present study investigated the anti-atherosclerotic and anti-inflammatory
properties of coptisine using apoE-/- mice as AS model. The atherosclerotic
plaque area of aorta, serum lipid profile and the expression of inflammatory
cytokines were determined. After coptisine treatment, the serum level of TC, TG
and LDL-C decreased; the serum level of IL-6, IL-1beta and TNF-alpha were
decreased; the mRNA levels of NF-kappaBp65, VCAM-1, ICAM-1, IL-6 and IL-1beta in
both aorta and liver were down-regulated; the p-p38 and p-JNK1/2 protein
expression level were decreased. Coptisine decreased atherosclerotic plaque area
significantly through both anti-inflammation and lipid lowering effect. The anti
inflammatory effect of coptisine is achieved through inhibiting activation of
MAPK signaling pathways and NF-kappaB nuclear translocation. Therefore,the
combined anti-inflammation and lipid lowering effect of coptisine attributed the
decreased atherosclerotic plaque area in coptisine treated apoE-/- mice. The
results of this study will afford a novel application for coptisine in the
treatment of atherosclerosis and other chronic inflammatory disease.
PMID- 28700977
TI - Neferine from Nelumbo nucifera modulates oxidative stress and cytokines
production during hypoxia in human peripheral blood mononuclear cells.
AB - Neferine, an alkaloid from N. nucifera has a broad range of pharmacological
activity. Hypoxia mediated stress is involved in the generation of inflammatory
responses and cell death. The present study evaluated the protective effect of
neferine against hypoxia-induced cytotoxicity, oxidative stress and inflammatory
response in human Peripheral Blood Mononuclear Cells (hPBMC). Cytotoxicity, as
determined by MTT, LDH and NO assays revealed that 24h of hypoxic exposure
results in 20% cell death (IC20) and compromising of cellular integrity, which
was restored to near control values by pretreatment with neferine. Oxidative
stress parameters such as lipid peroxidation and antioxidant enzymes indicated
that neferine exerted a protective effect on hypoxia-induced oxidative stress.
Hypoxia-induced Tumor Necrosis Factor-alpha (TNF-alpha), Interleukin 6 (IL-6),
and Interleukin 8 (IL-8) release were significantly reduced in the neferine
pretreated samples indicating its anti-inflammatory role. Our results demonstrate
for the first time that neferine exerts a cytoprotective effect against hypoxia
induced oxidative stress and inflammation in hPBMC.
PMID- 28700978
TI - Aptamer-assisted novel technologies for detecting bacterial pathogens.
AB - Nowadays, all people are at risk of infectious diseases that are mainly caused by
bacteria causing infection. There is a permanent demand for an appropriate
detection method that is affordable, practical, careful, rapid, sensitive,
efficient and economical. Aptamers are single stranded DNA or RNA
oligonucleotides, which can be recognized specifically and bind to their target
molecules and also, be exploited in diagnostic applications. Recently, aptamer
based systems have offered great potentials in applications for the recognition
of several important bacterial pathogens from clinical and food specimens. There
are several reports appraising the diagnostic applicability of aptamer-based
systems for the detection of pathogens. As for its excellent sensitivity, as well
as its rapid and efficient detectability, this technique may be practical to
indicate bacterial targets with less sample size and may consume less time than
traditional methods These systems offer a promising approach for the sensitive
and quick detection of food-borne and clinical agents. This review provides an
overview of aptamer-based methods as a novel approach for detecting bacterial
pathogens.
PMID- 28700984
TI - Immunosuppressive Treatment in C3 Glomerulopathy: Time to Reconsider Our
Approach.
PMID- 28700986
TI - Chemotherapy during Pregnancy: Cases of Hodgkin's and Non-Hodgkin's Lymphoma,
Chronic Myeloid Leukemia, Breast Cancer, Nasopharyngeal Cancer, and
Choriocarcinoma.
AB - BACKGROUND: The use of chemotherapeutics during pregnancy is a dilemma for both
the patient and the clinician. We report here our 11 years' experience with the
use of chemotherapy during pregnancy. PATIENTS: 13 patients undergoing
chemotherapy during their current pregnancy were evaluated. The medical data of 5
patients with hematologic malignancies (2 Hodgkin's, 2 non-Hodgkin's lymphoma,
and 1 chronic myeloid leukemia), 6 patients with breast cancer, 1 patients with
nasopharyngeal cancer, and 1 patient with choriocarcinoma were retrospectively
obtained from the 'perinatal database' of Hacettepe University for the period of
January 2002 through March 2016. RESULTS: 4 patients had a medical termination
due to teratologic effects. 4 patients had a vaginal delivery, and 5 patients
delivered by caesarean section. The 9 newborns who had been exposed to
chemotherapeutics were free of congenital anomalies. However, 1 of them died in
the early neonatal period due to multi-organ failure (nasopharyngeal cancer).
During the 2-year follow-up, we encountered 1 maternal mortality, which was due
to multi-organ failure in a non-Hodgkin's lymphoma patient. CONCLUSION:
Physicians must pay attention to potential teratologic problems, and should
carefully balance maternal and fetal risks. Selected chemotherapeutic agents can
be given in the 2nd and 3rd trimester without any major teratogenic risk. All 9
newborns in our study were free of anomalies, although 1 of them died in the
neonatal period.
PMID- 28700985
TI - Genes Involved in Long-Term Memory Are Expressed in Testis of Cryptorchid Boys
and Respond to GnRHa Treatment.
AB - It has been known for many years that boys with unilateral or bilateral
undescended testis (cryptorchidism) tend to have a low IQ, and those who belong
to the high infertility risk (HIR) group perform less well at school than low
infertility risk (LIR) patients. However, the molecular biological processes
underlying this phenomenon are not understood. In this study, we report the
outcome of testicular RNA profiling for genes involved in long-term memory
formation. We analyzed the histology and the transcriptome of testicular biopsies
from bilateral HIR cryptorchid boys, comparing those who received GnRHa treatment
for 6 months after the first surgery with those who did not receive GnRHa before
the second surgery. We found that GnRHa treatment alters the testicular mRNA
levels of neuronal genes that are involved in long-term memory and testosterone
synthesis. These data highlight a possible molecular link between cryptorchidism,
impaired mini-puberty, and diminished cognitive functions. Our results are
consistent with the hypothesis that hypogonadotropic hypogonadism in cryptorchid
boys with altered mini-puberty may affect neuronal genes important for memory and
learning, which could help explaining the negative correlation between
cryptorchidism and intellectual abilities.
PMID- 28700987
TI - Impact of Intravenous P2Y12-Receptor Inhibition with Cangrelor in Patients
Presenting with Acute Coronary Syndrome and Cardiogenic Shock - a Case Series.
AB - BACKGROUND/AIMS: Patients with acute coronary syndromes (ACS) presenting with
cardiogenic shock (CS) are at particular risk for death and adverse cardiac
events. Impaired effects and absorption of oral P2Y12-receptor inhibitors due to
decreased organ hypoperfusion or hypothermia and challenges regarding oral
administration contribute to this risk. We report a single center experience
regarding the use of intravenous P2Y12-receptor inhibitor cangrelor in patients
with CS treated with percutaneous coronary intervention (PCI). METHODS: Twelve
patients with ACS and CS undergoing PCI, not pretreated with oral P2Y12-receptor
inhibitors, were treated with cangrelor. Platelet inhibition was assessed by
multiple electrode aggregometry (MEA) before and after PCI, immediately and 2
hours after stopping the cangrelor infusion. RESULTS: Nine patients recovered
from their cardiogenic shock, 3 patients died. Platelet reactivity decreased from
65.9 (SD 41.0) U before PCI to 15.8 (SD 10.8) U after PCI, 13.4 (SD 7.7) U at the
end of infusion and 33.8 (SD 19.9) 2 hours after stopping the cangrelor infusion.
There was no non-responder under cangrelor infusion (MEA < 46 U). CONCLUSIONS:
Due to its favorable PK/PD profile, cangrelor overcomes problems with reduced
absorption and effects of oral P2Y12-receptor inhibitors and should be considered
for periprocedural treatment of patients with CS.
PMID- 28700988
TI - High-Dose Rituximab Ineffective for Focal Segmental Glomerulosclerosis: A Long
Term Observation Study.
AB - BACKGROUND: A beneficial effect of rituximab (RTX) on focal segmental
glomerulosclerosis (FSGS) in pediatric patients or in transplant recipients has
been reported in isolated cases. However, the use of RTX in adult patients with
idiopathic FSGS needs further investigation. METHODS: Eight patients who had
biopsy-proven FSGS (63.9 +/- 14.0, range 40-81 years, 4 women, 4 men) with major
risk factors precluding corticosteroids or conventional immunosuppression were
treated with a high dose of RTX (8 weekly doses of 375 mg/m2) and prospectively
followed up for at least 2 years (29.1 +/- 8.8 months, range 24-42 months).
RESULTS: RTX failed to improve proteinuria in 7 out of 8 patients, who had
persistent nephrotic proteinuria. In one case, a rapidly deteriorating renal
function was also observed. Only one patient showed an improvement in renal
function and a remarkable reduction in proteinuria. There were no differences in
clinical or laboratory characteristics or in the CD20 B lymphocyte count after
RTX between the responder and the 7 nonresponder patients. CONCLUSIONS: Only a
minority (1 of 8) in our series of adult patients with FSGS showed positive
effects of high doses of RTX. Future studies are warranted to investigate more
promising therapeutic options in the management of FSGS.
PMID- 28700989
TI - DoriTool: A Bioinformatics Integrative Tool for Post-Association Functional
Annotation.
AB - The emergence of high-throughput data in biology has increased the need for
functional in silico analysis and prompted the development of integrative
bioinformatics tools to facilitate the obtainment of biologically meaningful
data. In this paper, we present DoriTool, a comprehensive, easy, and friendly
pipeline integrating biological data from different functional tools. The tool
was designed with the aim to maximize reproducibility and reduce the working time
of the researchers, especially of those with limited bioinformatics skills, and
to help them with the interpretation of the results. DoriTool is based upon an
integrative strategy implemented following a modular design pattern. Using
scripts written in Bash, Perl and R, it performs a functional in silico analysis
annotation at mutation/variant level, gene level, pathway level and network level
by combining up-to-date functional and genomic data and integrating also third
party bioinformatics tools in a pipeline. DoriTool uses GRCh37 human assembly and
online mode. DoriTool provides nice visual reports including variant annotation,
linkage disequilibrium proxies, gene annotation, gene ontology analysis,
expression quantitative trait loci results from Genotype-Tissue Expression (GTEx)
and coloured pathways. Here, we also show DoriTool functionalities by applying it
to a dataset of 13 variants associated with prostate cancer. Project development,
released code libraries, GitHub repository (https://github.com/doritool) and
documentation are hosted at https://doritool.github.io/. DoriTool is, to our
knowledge, the most complete bioinformatics tool offering functional in silico
annotation of variants previously associated with a trait of interest, shedding
light on the underlying biology and helping the researchers in the interpretation
and discussion of the results.
PMID- 28700990
TI - Oncologic Response and Hospitalization Rate of Patients Receiving Cabazitaxel in
the Fourth-Line and Beyond in Castration-Resistant Prostate Cancer: Analysis of a
Retrospective Cohort and a Structured Literature Review.
AB - BACKGROUND: Limited data are available for the use of agents in metastatic
castration-resistant prostate cancer (mCRPC) beyond the third-line. We provide
data during treatment with cabazitaxel (CAB), helping to improve the informed
consent process. PATIENTS AND METHODS: We retrospectively reviewed patients
treated with fourth-line or beyond CAB for mCRPC after failure of previous
therapies with docetaxel, abiraterone acetate, enzalutamide and/or radium-223.
The progression-free survival (PFS) and the overall survival (OS) were estimated
using the Kaplan-Meier method and compared to published data based on a
structured literature review. The hospitalization rate was recorded. Factors
influencing 6-months OS were analyzed. RESULTS: Fifteen patients were identified
at 4 institutions and included in the analysis. The median PFS was 104 days
(range 47-397 days). The median time to death was 10 months (range 2-16). PFS and
OS data are in accordance with 17 published patients so far. During the therapy,
eleven (73%) of the patients were hospitalized. Prostate-specific antigen (PSA,
500 units; hazards ratio [HR] 1.491, 95% CI 1.000-2.0175), white blood cell count
(HR 0.425, 95% CI 0.108-0.952), hemoglobin (HR 0.6014, 95% CI 0.2942-1.0758), and
alkaline phosphatase (100 units; HR 1.0964, 95% CI 1.000-1.2859) correlate with 6
months OS. CONCLUSIONS: CAB beyond the third-line is often accompanied by
hospitalization. PFS is a significant proportion of the median time of OS. The
baseline laboratory might be a good indicator for the decision between CAB and
best-supportive care.
PMID- 28700991
TI - Strain Differences and Effects of Environmental Manipulation on Astrocytes (Glial
Fibrillary Acidic Protein), Glucocorticoid Receptor, and Microglia (Iba1)
Immunoreactivity between Wistar-Kyoto and Wistar Females.
AB - BACKGROUND: Depression is often associated with an increase in hypothalamic
pituitary-adrenal (HPA) axis reactivity and immune response. To investigate this
relationship, we examined the consequences of environmental manipulation on the
neural correlates of the HPA axis and immune response in an animal model of
depression, the Wistar-Kyoto (WKY) rat. Additionally, female animals are often
overlooked in preclinical research because of the hormone fluctuations inherent
in the estrous cycle. METHODS: Female rats were randomly assigned to 1 of 3
environments for 30 days: (1) environmental enrichment (EE), (2) standard housing
(SH), and (3) isolated housing (IH). Immunoreactivity of astrocytes (glial
fibrillary acidic protein [GFAP]), glucocorticoid receptors (GRs), and microglia
(Iba1) in the hippocampus and amygdala were measured using immunohistochemistry.
RESULTS: WKY animals had significantly more GR staining area and Iba1 staining
intensity and area in the CA1 of the hippocampus. In enriched Wistar rats, GFAP
staining intensity and area were greater in the CA1. A trend towards a greater
percent of area stained with GR was found in WKY animals as compared to that of
the Wistar animals. This was due to WKY females in EE having significantly higher
GR staining intensity and area in the amygdala as compared to that of animals in
SH. DISCUSSION: These strain differences lend support to the use of WKY animals
as an animal model of depression. Furthermore, due to the effects of EE on GFAP
and GR staining in WKY females, we suggest that EE can be used as an intervention
to potentially alleviate the negative effects of depression.
PMID- 28700992
TI - Natural History of Fetal Lower Urinary Tract Obstruction with Normal Amniotic
Fluid Volume at Initial Diagnosis.
AB - OBJECTIVE: The aim of this study was to define the natural history of lower
urinary tract obstruction (LUTO) with normal midgestational amniotic fluid
volumes. MATERIALS AND METHODS: We performed a retrospective review of 32
consecutive patients with LUTO with normal midgestational amniotic fluid volume
followed at 11 North American Fetal Therapy Network (NAFTNet) centers from August
2007 to May 2012. Normal amniotic fluid volume was defined as an amniotic fluid
index (AFI) of >=9 cm. RESULTS: The mean gestational age (GA) and AFI at
enrollment were 23.1 +/- 2.1 weeks and 15.8 +/- 3.9 cm, respectively. The mean GA
at delivery was 37.3 +/- 2.8 weeks. The mean creatinine level at discharge was
1.2 +/- 0.8 mg/dL. Perinatal survival was 97%. Twenty-five patients returned for
serial postnatal assessment. Renal replacement therapy (RRT) was required in 32%.
Development of oligohydramnios and/or anhydramnios, development of cortical renal
cysts, posterior urethral valves, prematurity, and prolonged neonatal intensive
care unit stay were associated with need for RRT (p < 0.05) by univariate
analysis. By multivariate analysis, preterm delivery remained predictive of need
for RRT (p = 0.004). CONCLUSION: Prenatal diagnosis of LUTO with normal
midgestational amniotic fluid volumes is associated with acceptable renal
function in the majority of patients. Approximately one-third of these children
require RRT. Surrogate markers of disease severity appear to be predictive of
need for RRT.
PMID- 28700993
TI - The Impact of Oxidative Stress Factors on the Viability, Senescence, and
Methylation Status of Olfactory Bulb-Derived Glial Cells Isolated from Human
Cadaver Donors.
AB - The olfactory bulb (OB) is a unique structure in the central nervous system that
retains the ability to create new neuronal connections. Glial cells isolated from
the OB have been recently considered as a novel and promising tool to establish
an effective therapy for central nervous system injuries. Due to the hindered
access to autologous tissue for cell isolation, an allogeneic source of tissues
obtained postmortem has been proposed. In this study, we focused on the
morphological and molecular characteristics of human OB-derived glial cells
isolated postmortem, at different time points after a donor's death. We evaluated
the proliferative activity of the isolated cells, and investigated the
ultrastructure of the mitochondria, the accumulation of intracellular reactive
oxygen species, and the activity of superoxide dismutase. The data obtained
clearly indicate that the duration of ischemia is crucial for the
viability/senescence rate of OB-derived glial cells. The OB can be isolated
during autopsy and still stand as a source of viable glial cells, but ischemia
duration is a major factor limiting its potential usefulness in therapies.
PMID- 28700994
TI - Brain Metastasis from Colorectal Cancer: Predictors and Treatment Outcomes.
AB - OBJECTIVE: Difficulties are associated with the management of brain metastasis
(BM), which portends a poor prognosis in the treatment of colorectal cancer
(CRC). The aim of the present study was to identify risk factors for BM in CRC
and evaluate the outcomes of various treatment modalities. METHODS: We
retrospectively reviewed data on a total of 2,238 patients with primary CRC who
underwent surgical resection at our hospital between 1999 and 2014. Predictive
factors for BM and prognostic factors after the diagnosis of BM were examined by
univariate and multivariate analyses using Cox proportional hazards models.
RESULTS: Three patients (0.1%) had BM at the initial diagnosis, and 23 patients
(1.2%) developed metachronous BM during the median follow-up period of 44.6
months. Lung and bone metastases were identified as independent predictive
factors for BM. Median survival after the diagnosis of BM was 7.4 months.
Stereotactic radiosurgery, administered to 41% of the patients with BM, was
associated with a better postdiagnostic survival. CONCLUSION: CRC patients with
metastasis to the lung or bone were at a higher risk of BM. Because the survival
is still limited, it is crucial to determine the treatment strategy in
consideration of the characteristics of each therapy and quality of life in CRC
patients with BM.
PMID- 28700995
TI - Extended Pancreatectomy: Does It Have a Role in the Contemporary Management of
Pancreatic Adenocarcinoma?
AB - BACKGROUND: Pancreatic cancer is a low-incident but highly mortal disease.
Surgery is still the preferred treatment option for resectable pancreatic cancer
as it offers the only realistic chance for cure. As many patients present with
locally advanced disease, which is generally considered as not amenable to
surgical treatment, it is important to know the limits of surgical therapy in
this disease. METHODS: In this review, the indication and outcomes of extended
pancreatectomies as well as the alternative treatment options for locally
advanced pancreatic cancer are described. Furthermore, controversies as well as
ongoing and future directions for the treatment options of locally advanced
pancreatic cancer are discussed. RESULTS: Extended pancreatectomy can be
performed with higher morbidity and mortality rates in patients with locally
advanced pancreatic cancer compared to patients undergoing formal pancreatic
resections. These procedures offer significant advantages with respect to both
perioperative results and to long-term outcome when compared to chemotherapy.
CONCLUSION: Due to the higher morbidity and mortality rates, these operations
should be limited to specialist units with great experience in pancreatic surgery
as well as experience in peri- and post-operative management of patients with
pancreatic diseases.
PMID- 28700996
TI - Immunosuppressive Treatment in C3 Glomerulopathy: Is it Really Effective?
AB - BACKGROUND: C3 glomerulopathy (C3GP) is a recently identified and described
disease that has a high risk of progressing into end-stage renal disease. We
aimed to evaluate the effects of various immunosuppressive regimens on C3GP
progression because there are conflicting data on the treatment modalities.
METHODS: In this retrospective study of 66 patients with C3GP, 27 patients
received mycophenolate mofetil (MMF)-based treatment, 23 received non-MMF-based
treatment (prednisolone or cyclophosphamide), and 16 received conservative care.
The study groups were compared with each other with specific focus on primary
outcomes defined as (1) kidney failure and (2) estimated glomerular filtration
rate (eGFR) decline >=50% from the baseline value. RESULTS: Overall, 17 (25.8%)
patients reached the primary outcome after a median period of 28 months. The
number of patients who reached the primary outcome were similar among the study
groups (MMF-based: 8/27 [29.6%], non-MMF-based: 4/23 [17.4%], and conservative
care: 5/16 [31.3%], p = 0.520). In the Cox regression analysis, age (HR 0.912, p
= 0.006), eGFR (HR 0.945, p = 0.001), and proteinuria levels (HR 1.418, p =
0.015) at the time of biopsy, percentage of crescentic (HR 1.035, p = 0.001) and
sclerotic glomeruli (HR 1.041, p = 0.006), severity of interstitial fibrosis (HR
1.981, p = 0.048), as well as no remission of proteinuria (HR 2.418, p = 0.002)
predicted the primary outcome. CONCLUSION: Although patients receiving
immunosuppressive treatments had higher proteinuria and lower serum albumin at
baseline, there were no differences between these patients and those receiving
conservative care alone in proteinuria remission or in the decline of renal
function. Younger age, higher proteinuria, lower eGFR, and the presence of
crescentic and sclerotic glomeruli, severity of interstitial fibrosis, and no
remission of proteinuria predicted the progression of kidney disease.
PMID- 28700997
TI - Nobiletin, a Polymethoxy Flavonoid, Protects Against Cardiac Hypertrophy Induced
by Pressure-Overload via Inhibition of NAPDH Oxidases and Endoplasmic Reticulum
Stress.
AB - BACKGROUND/AIMS: An increase in oxidative stress has been implicated in the
pathophysiology of pressure-overload induced cardiac hypertrophy. Nobiletin
(NOB), extracted from the fruit peel of citrus, possesses anti-oxidative
property. Our study aimed to investigate the protective role of NOB in the
progression of cardiac hypertrophy in vivo and in vitro. METHODS: Mice received
aortic banding (AB) operation to induce cardiac hypertrophy. Experimental groups
were as follows: sham+vehicle (VEH/SH), sham+NOB (NOB/SH), AB+vehicle (VEH/AB),
and AB+ NOB (NOB/AB). Animals (n = 15 per group) were treated with vehicle or NOB
(50 mg/kg) for 4 weeks after disease onset. RESULTS: NOB prevented cardiac
hypertrophy induced by aortic banding (AB), as assessed by the cross-sectional
area of cardiomyocytes, heart weight-to-body weight ratio, gene expression of
hypertrophic markers and cardiac function. In addition, NOB supplementation
blunted the increased expression of NAPDH oxidase (NOX) 2 and NOX4 and mitigated
endoplasmic reticulum (ER) stress and myocyte apoptosis in cardiac hypertrophy.
Furthermore, NOB treatment attenuated the neonatal rat cardiomyocyte (NRCM)
hypertrophic response stimulated by phenylephrine (PE) and alleviated ER stress.
However, our data showed that NOB dramatically inhibited NOX2 expression but not
NOX4 in vitro. Finally, we found that knockdown of NOX2 attenuated ER stress in
NRCMs stimulated by PE. CONCLUSIONS: Inhibition of oxidative and ER stress by NOB
in the myocardium may represent a potential therapy for cardiac hypertrophy.
Moreover, there is a direct role of NOX2 in regulating ER stress stimulated by
PE.
PMID- 28700998
TI - A Decrease of Histone Deacetylase 6 Expression Caused by Helicobacter Pylori
Infection is Associated with Oncogenic Transformation in Gastric Cancer.
AB - BACKGROUND: Histone deacetylase 6 (HDAC6) plays a role in the progression of many
tumors. However, the relationship between the level of HDAC6 expression and
gastric tumorigenesis is still unclear. Here, we illustrate the potential
correlation between Helicobacter pylori (HP) infection and the variation of HDAC6
expression in different gastric lesions, as well as the clinical significance of
HDAC6 expression in gastric cancer (GC) patients. MATERIALS AND METHODS: Between
2011 and 2016, 364 patients with different types of gastric lesions were enrolled
in Baotou City Central Hospital. Immunostaining of HDAC6 expression and HP
infection were performed in the following cohort including 21 normal tissues
(Normal); 40 samples with chronic superficial gastritis (CSG); 106 with chronic
atrophic gastritis (CAG); 94 with intestinal metaplasia (IM); 64 with dysplasia
(DYS) and 39 with gastric cancer (GC). Survival analysis was performed in another
80 GC patients using the Kaplan-Meier method and multivariate Cox regression
analyses. The level of HDAC6 expression was determined by Real-time PCR, Western
blotting and IHC staining in gastric cell lines and tissues. Furthermore, the
correlation between HDAC6 expression and clinicopathological features and
prognosis was analyzed in the GC cohort. HP strains were lavaged into Kunming
mice to investigate the effects of HP infection on the expression of different
HDAC members in this mouse model. RESULTS: Higher levels of HDAC6 expression were
detected in normal and premalignant lesions than in the GC tissues (p<0.01), and
decreased HDAC6 expression was associated with HP infection and TNM stage (p<0.01
and p=0.048, respectively). Multivariate analysis revealed that HDAC6 expression
was an independent predictor of the outcome of GC patients (p=0.04). HP mediated
HDAC6 expression in the cell lines and KM mice. HP infection could promote HDAC1
and HDAC4 expression as determined by Western blotting. CONCLUSIONS: HDAC6 is a
promising biomarker for early diagnosis and prognosis during the oncogenic
transformation of gastric cancer.
PMID- 28700999
TI - Genome-Wide Association Study of MKI67 Expression and its Clinical Implications
in HBV-Related Hepatocellular Carcinoma in Southern China.
AB - BACKGROUND/AIMS: Hepatocellular carcinoma (HCC) is a common malignant tumor with
a high rate of recurrence. Immunohistochemical analysis of the marker of
proliferation Ki-67 (MKI67) is used to assess proliferation activity of HCC The
regulation of MKI67 expression remains unclear in HCC This study aims to explore
the association between MKI67 expression and gene variants. METHODS: A total of
195 hepatitis B virus (HBV)-related HCC patients were genotyped using Illumina
HumanExome BeadChip-12-1_A (242,901 markers). An independent cohort (97 subjects)
validated the association of polymorphism determinants and candidate genes with
MKI67 expression. The relationships between MKI67 with p53 and variants of
candidate genes in the clinical outcomes of HCC patients were analyzed. RESULTS:
We found that MKI67 combined with p53 was associated with a 3-year recurrence
free survival and five variants near TTN and CCDC8 were associated with MKI67
expression. TTN harboring rs2288563-TT and rs2562832-AA+CA indicated a favorable
outcome for HCC patients. CONCLUSION: Variants near TTN and CCDC8 were associated
with MKI67 expression, and rs2288563 and rs2562832 in TTN are potential
biomarkers for the prediction of clinical outcomes in HBV-related HCC patients.
PMID- 28701000
TI - Decreased Expression of Integrin Subunits alpha3, alpha6, and alpha8 in the
Branching Airway Mesenchyme of Nitrofen-Induced Hypoplastic Lungs.
AB - INTRODUCTION: Pulmonary hypoplasia (PH), characterized by smaller lung size and
reduced airway branching, remains a major cause of neonatal mortality in newborns
with congenital diaphragmatic hernia (CDH). Integrin-mediated cell-matrix
interactions play an essential role in the fetal lung mesenchyme by stimulating
branching morphogenesis. Mice lacking integrin subunits alpha3 (Itga3) and alpha6
(Itga6) exhibit severe PH. Furthermore, Itga8-knockout mice show defective airway
branching, suggesting that Itga3, Itga6, and Itga8 are crucial for fetal lung
development. We hypothesized that expression of Itga3, Itga6, and Itga8 is
decreased in the branching airway mesenchyme of hypoplastic rat lungs in the
nitrofen-induced CDH model. MATERIALS AND METHODS: Time-mated rats received
nitrofen or vehicle on gestational day 9 (D9). Fetuses were sacrificed on D15,
D18, and D21, and dissected lungs were divided into control and nitrofen-exposed
specimens (n = 12 per time-point and group, respectively). Pulmonary gene
expression of Itga3, Itga6, and Itga8 was analyzed by quantitative real-time
polymerase chain reaction. Immunofluorescence double-staining for Itga3, Itga6,
and Itga8 was combined with the mesenchymal marker Fgf10 to evaluate protein
expression and localization in branching airway tissue. RESULTS: Relative mRNA
expression of Itga3, Itga6, and Itga8 was significantly decreased in lungs of
nitrofen-exposed fetuses on D15, D18, and D21 compared with controls. Confocal
laser scanning microscopy showed markedly diminished immunofluorescence of Itga3,
Itga6, and Itga8 mainly in mesenchymal cells surrounding branching airways of
nitrofen-exposed fetuses on D15, D18, and D21 compared with controls. CONCLUSION:
Decreased expression of Itga3, Itga6, and Itga8 in the pulmonary mesenchyme may
lead to disruptions in airway branching morphogenesis, thus contributing to PH in
the nitrofen-induced CDH model.
PMID- 28701001
TI - Downregulated Elastin Microfibril Interfacer 1 Expression in the Pulmonary
Vasculature of Experimental Congenital Diaphragmatic Hernia.
AB - AIM: Pulmonary hypertension (PH) is a severe complication of congenital
diaphragmatic hernia (CDH). Transforming growth factor-beta (TGFbeta) signaling
is suggested to be involved in PH development by regulating embryonic
angiogenesis, cell proliferation, and cell differentiation. Altered TGFbeta
signaling has been demonstrated in experimental CDH lungs. Elastin microfibril
interfacer 1 (Emilin-1) is an extracellular matrix glycoprotein expressed in
endothelial and vascular smooth muscle cells and known to regulate TGFbeta
processing and arterial diameter. We designed this study to investigate the
pulmonary vascular expression of Emilin-1 in nitrofen-induced CDH rats. MATERIALS
AND METHODS: Following ethical approval (REC913b, REC1103), time-pregnant
Sprague Dawley rats received nitrofen or vehicle on gestational day 9 (D9).
Fetuses were sacrificed on D21 and divided into CDH group and control group.
Quantitative real-time polymerase chain reaction (n = 11 each group), Western
blot analysis, and confocal microscopy were used to determine the gene and
protein expression of Emilin-1. MAIN RESULTS: Relative Emilin-1 messenger RNA
(ribonucleic acid) levels were significantly downregulated in CDH lung tissue
compared with controls (CDH: 0.043 +/- 0.003; control: 0.067 +/- 0.004; p <
0.001). Western blotting confirmed the decreased pulmonary Emilin-1 protein
expression in CDH lungs. Confocal microscopy demonstrated a markedly diminished
expression of Emilin-1 in the CDH pulmonary vasculature compared with controls.
CONCLUSION: To our knowledge, this study demonstrates for the first time a
decreased Emilin-1 gene and protein expression in the pulmonary vasculature of
nitrofen-induced CDH. Emilin-1 deficiency through its interaction with TGFbeta
may result in abnormal vascular remodeling resulting in PH in this model.
PMID- 28701002
TI - Atropine Treatment for Hypertrophic Pyloric Stenosis: A Systematic Review and
Meta-Analysis.
AB - INTRODUCTION: Several authors have reported the use of atropine as an
alternative treatment to pyloromyotomy in infants with hypertrophic pyloric
stenosis (HPS). Our aims were to review the efficacy of atropine in treating HPS
and to compare atropine therapy versus pyloromyotomy. MATERIALS AND METHODS:
Using a defined search strategy (PubMed, MEDLINE, OVID, Embase, Cochrane
databases), two investigators independently identified studies reporting the use
of atropine for HPS. Case reports and opinion articles were excluded. Outcome
measures included success rate, side effects, and length of hospital stay.
Maneuvers were compared using Fisher's exact test, and meta-analysis was
conducted using RevMan 5.3. Data are expressed as mean +/- standard deviation.
RESULTS: Systematic review: of 2,524 abstracts screened, 51 full-text articles
were analyzed. There were no prospective or randomized studies. Twelve articles
(508 infants) reported HPS resolution using atropine in 402 (79.1%) patients.
Atropine side effects were documented in 38/251 (15.1%) infants and included
tachycardia, increased transaminases, and flushed skin. Meta-analysis: five
studies compared atropine treatment (293 infants) with pyloromyotomy (537
infants). Pyloromyotomy had higher success rate (100%) than atropine (80.8%; p <
0.01) and shorter hospital stay (5.6 +/- 2.3 vs. 10.3 +/- 3.8 days, respectively;
p < 0.0001). CONCLUSION: Comparative but nonrandomized studies indicate that
atropine is less effective than pyloromyotomy to treat infants with HPS.
Currently, there is no evidence-based literature to support atropine treatment in
these infants. To our knowledge, atropine should be reserved for patients unfit
for general anesthesia or surgery.
PMID- 28701003
TI - [The Impact of Migration Background on Health: Results of the Austrian Health
Interview Survey (ATHIS 2014)].
AB - Objectives Previous research has shown migrants to have a poorer health status
than those without a migration background in many respects. So far, it is not
completely clear whether the poorer health results of migrants are mainly the
cause of their socioeconomic status (SES), which on average is lower than the SES
of people without a migration background. The present study explores the question
whether the fact of having a migration background has an impact on health, even
though SES and health-related behavior are taken into account. Methods Based on
data from the current Austrian Health Interview Survey (ATHIS 2014) multiple
linear regression models, adjusted for age and stratified by gender, were
conducted. The dependent variables were physical quality of life, psychological
quality ofZ life, self-perceived health, body-mass-index (BMI),
headaches/musculoskeletal pain, and diabetes/cardiovascular diseases (n=15,748).
Results We found differences in health between men and women with migration
background and men and women without migration background. After adjusting for
age, SES and health-related behavior, almost all of the revealed differences got
smaller. The strongest link between migrant status and health status was detected
for migrants from countries with a lower Inequality-adjusted Human Development
Index (IHDI) in comparison to Austria. Conclusion The results lead to the
conclusion that although SES and health-related behavior do not fully explain
health differences between people with migration background and those without,
they can explain the differences to a large extent. However, for the health
status of migrants who stem from countries with a lower standard of living and a
weaker distributive justice in comparison to Austria, further factors might play
a role. With respect to this group of migrants, differences in health compared to
non-migrants are not solely attributable to SES and health-related behavior.
PMID- 28701004
TI - En Plaque Pituitary Adenoma within a Rathke's Cleft Cyst: Report of Three Cases.
AB - Concomitant pituitary adenomas and Rathke's cleft cysts (RCCs) are rare. These
coexisting lesions are difficult to diagnose preoperatively due to their variable
signal intensity on magnetic resonance imaging (MRI) and position of the RCC. We
describe three cases of coexisting pituitary adenoma and RCC, and review the
relevant literature. In our cases, the RCCs were relatively large and the en
plaque adenomas appeared as enhanced cyst walls on MRI examination. We also
report the clinical, radiologic, surgical, and histopathologic findings of each
case.
PMID- 28701005
TI - Morphological Effect on Wall Shear Stress in Intracranial Aneurysms.
AB - BACKGROUND AND STUDY AIMS: Both high and low wall shear stress (WSS) play
important roles in the development and rupture of intracranial aneurysms (IAs).
This study aimed to determine the morphological factors that affect WSS in the IA
and the parent artery. MATERIAL AND METHODS: We studied a total of 66 IAs with
three-dimensional imaging. Computational fluid dynamics (CFD) models were
constructed and used to characterize the hemodynamics quantitatively. Aneurysms
were grouped according to the mean neck width. The associations among
hemodynamics and morphology were analyzed. RESULTS: Aspect ratio was correlated
to lowest WSS (r = - 0.576), aneurysm-to-parent vessel (A-P) WSS ratio (r = -
0.500), and lowest-parent vessel (L-P) WSS ratio (r = - 0.575). Height-to-width
ratio and height were correlated to WSS. Mean aneurysm WSS (p = 0.023), lowest
WSS (p < 0.0001), highest-to-lowest WSS ratio (p = 0.004), L-P WSS ratio (p <
0.0001), highest-parent vessel (H-P) WSS ratio (p = 0.008), A-P WSS ratio (p <
0.001), and height (p < 0.001) were different between the two groups of aneurysms
that were divided by the relationship between the diameters of the aneurysms and
the necks. Multivariable analysis showed that the lowest WSS (p = 0.028) and A-P
WSS ratio (p = 0.001) were independently associated with neck width. CONCLUSION:
Morphological characteristics are associated with IA and parent vessel WSS.
Aneurysms with different neck widths have different hemodynamics. These results
could help in understanding the progression of IA and in building predictive
models for IA rupture.
PMID- 28701006
TI - How Accurate is Intraoperative Alignment Measurement with a Navigation System in
Primary Total Knee Arthroplasty?
AB - The primary objective was to compare the intraoperative data assessed by
OrthoPilot (Aesculap AG, Tuttlingen, Germany) with postoperative coronal and
sagittal long-leg standing radiographs. The secondary objective was to evaluate
the influence of sex and body mass index (BMI) on the accuracy and effectiveness
of the implantation of the knee prosthesis by OrthoPilot. We included 75 patients
in our investigation. Participants received an e.motion (Aesculap AG) knee
prosthesis using the OrthoPilot navigation system. Postoperative long-leg
standing anteroposterior and lateral radiographs were performed. We compared the
intraoperative navigational data with postoperative determined angles of knee
geometry. We also compared the sex and BMI of participants to their difference
between intraoperative and postoperative measurements to test for an association.
We found a difference between intraoperative data and radiographs of 1.8 degrees
for the hip-knee-ankle angle. The intraoperative lateral distal femoral angle and
medial proximal tibial angle differed from the radiological analysis by 1.2
degrees, respectively. The lateral views revealed a difference of 1.6 degrees for
femur lateral and 1.4 degrees for the tibia lateral. There was no significant (p
> 0.05) influence of the parameters BMI and sex of the patients on these values.
Our results showed that the implemented intraoperative navigation system is
reliable. It does not differ on average from postoperative radiographs by more
than 1.8 degrees. The findings of our study suggest that a correct postoperative
alignment can be achieved in both high and low BMI participants if a precise
range is maintained during the surgery.
PMID- 28701008
TI - Asymmetric Tibial Component Improved the Coverage and Rotation of the Tibial
Component in a Medial Pivot Total Knee Prosthesis.
AB - Malrotation of tibial components is one of the important causes of failure in
total knee arthroplasty. The aim of this study is to determine the relationship
between tibial rotational positioning and coverage of the tibial surface during
the operation, using a symmetric and newly introduced asymmetric medial pivot
tibial components. The coverage and overhang were compared between a symmetric
component (Advance medial pivot) and a newly introduced asymmetric medial pivot
tibial component (Evolution medial pivot) in 31 knees during the operation. When
the tibial component was placed parallel to the anteroposterior (AP) axis, the
uncovered width in the posteromedial part using a symmetric design was larger
than that using an asymmetric design (p < 0.01). Overhang in the posterolateral
part was observed in 42% for a symmetric design and 3% for an asymmetric design
(p < 0.01). When the component was placed in malrotation (10 degrees internal to
the AP axis), overhang in the posteromedial part was observed in 6% for a
symmetric design and in 71% for an asymmetric design (p < 0.01). The tibial
rotation parallel to the AP axis and maximizing coverage of the tibial surface
conflict in a symmetric design, but are compatible in an asymmetric design. An
asymmetric tibial component is expected to improve the coverage and the
rotational positioning of medial pivot total knee prosthesis.
PMID- 28701007
TI - Variance in Anterior Cruciate Ligament Reconstruction Graft Selection based on
Patient Demographics and Location within the Multicenter Orthopaedic Outcomes
Network Cohort.
AB - The purpose of this study is to determine whether any regional or age-related
patterns exist in graft choice for patients undergoing primary anterior cruciate
ligament reconstruction (ACLR) within a large multicenter consortium. A
retrospective cohort study was performed using data collected from the
Multicenter Orthopaedic Outcomes Network (MOON) on patients having undergone
primary ACLR. Patients were stratified by age group (younger than 20, 20-29, 30
39, 40-49, and 50+ years) and four demographic regions (Midwest, Southeast,
Northeast, and West). A total of 2,149 patients (1,288 males, 861 females) were
included. At least 70% of the patients were treated by a single surgeon in three
of the four demographic regions. There were no clinically significant differences
in body mass index (BMI), and no statistically significant differences in Marx
activity rating scale (p > 0.05) between regions within any particular age group.
There were significant differences in the proportion of autografts versus
allografts used for primary ACLR between regions in every age group (p < 0.01).
There were also significant differences in autograft (p < 0.001) and allograft (p
< 0.001) harvest location based on demographic region. The Southeast and
Northeast were more likely to use bone-patellar-tendon-bone autograft while the
West and Midwest were likely to use hamstring autograft. Within our consortium,
regional patterns exist both in autograft versus allograft use in patients
undergoing primary ACLR, as well as harvest location of autografts and
allografts. Given the similarities in average patient BMI and activity level
between regions, as well as the single surgeon influence in three of the four
regions, the regional patterns in graft use are likely due to surgeon preference.
PMID- 28701009
TI - Modified Intervastus Approach to the Knee.
AB - The modified intervastus approach to the anterior knee is an approach that may be
used in the majority of patients undergoing total knee arthroplasty. This article
presents the first description of this approach. The advantages of this approach
include its extensile nature, similar to a medial parapatellar approach, and
preservation of the extensor mechanism and the vastus medialis, leading to a more
rapid return to active knee extension than is traditionally observed. The
approach is also simple to perform, easy to close, and is compatible with more
extensile approaches such as a quadriceps snip if required in revision scenarios.
PMID- 28701010
TI - How Do Axial Scan Orientation Deviations Affect the Measurements of Knee
Anatomical Parameters Associated with Patellofemoral Instability? A Simulated
Computed Tomography Study.
AB - The purpose of this study was to detect the correlation between axial scan
orientation discrepancy and the knee anatomical parameters associated with
patellofemoral instability during computed tomography (CT) scanning. CT scan data
of 16 knees from 16 healthy subjects were retrieved. The reslicing processes were
performed to simulate different axial scan orientations generated due to leg
adduction/abduction during CT scanning. Eight parameters (tibial tubercle to
trochlear groove [TT-TG], tibial tubercle to posterior cruciate ligament [TT
PCL], patellar tilt, lateral trochlear inclination, sulcus angle, trochlear
depth, trochlear facet asymmetry, and trochlear condyle asymmetry) of five angles
(neutral zero, 4/8 degrees of adduction and 4/8 degrees abduction) were
quantified. All eight parameters showed varying degrees of deviations to the
different axial scan orientations. TT-TG, patellar tilt, lateral trochlear
inclination, and trochlear condyle asymmetry were relatively sensitive to axial
scan orientation changes, whereas TT-PCL, sulcus angle, trochlear depth, and
trochlear facet asymmetry were relatively insensitive. Although the sensitivities
are various, surgeons should be aware of this situation and make necessary
corrections.
PMID- 28701011
TI - Action Plan for Prolongation of Nephrogenesis in Preterm and Growth Restricted
Babies: Explore Ultrastructure of the Nephrogenic Zone, Identify a Molecular
Target, Select a Viable Drug and Find a Path for Administration.
AB - A large amount of investigations informs about primary steps of mammalian kidney
development such as anlage of the organ and initial nephron formation, while only
few data exists about the late phase of human kidney development. In particular,
little attention was up to date addressed to the decrease of morphogenic activity
in the nephrogenic zone short before birth and the vanishing of all stem cell
niches aligned beyond the organ capsule. There is evidence that molecular
controlling of this normal but degenerative developmental process also plays a
decisive role in the kidneys of preterm and growth restricted babies. Although
they are born in a phase of active nephrogenesis, a substantial percentage of
them evolves oligonephropathy, formation of atypical glomeruli and immaturity of
parenchyma. Pathologic findings point out that independent from chemical nature
all suspected hampering influences sublimate in the nephrogenic zone. However, it
is unknown, whether impaired nephrogenesis is locally caused by harming
interstitial fluid, disturbance of morphogen signaling, unbalanced synthesis of
extracellular matrix or limited cell to cell communication. Thus, first of all
these issues must be resolved, then save application of medicines prolonging
nephrogenesis waits for realization. Due to the unexpectedly complex microanatomy
and physiology of the nephrogenic zone, it will be a particular challenge for the
future.
PMID- 28701012
TI - [Diagnosis of Periprosthetic Joint Infection of Shoulder Arthroplasties].
AB - Periprosthetic joint infection of shoulder arthroplasties is one of the most
frequent reasons for pain and revision surgery of shoulder arthroplasties.
Propionibacterium acnes is one of the commonest microorganisms causing
periprosthetic joint infection in shoulder arthroplasties. It is difficult to
detect this slow growing microorganism. This paper gives an overview of the
different diagnostic methods. A combination of unspecific and specific tests
(detection of microorganism and sensitivity to antibiotics) is helpful in
identifying a periprosthetic shoulder infection. Aspiration of the joint can
combine different unspecific and specific tests. In patients with punctio sicca
and suspected periprosthetic joint infection, we recommend biopsy of
periprosthetic tissue.
PMID- 28701013
TI - ?
PMID- 28701014
TI - [Spacer, Aerosol Therapy through Space and Time].
AB - Aim of the literature review Within this review, results of a literature analysis
on the application of spacers with pressurized metered dose inhalers (pMDI) are
described and evaluated. Methods Next to an extensive revision on effects of
spacers, the impacts of current guidelines and the conditions for product
authorisations on the use of spacers are described which result from the
interplay of characteristics from dose inhalers with a spacer. Results Spacers
are generally useful to avoid coordination problems concerning the actuation of a
pMDI at the beginning of an inhalation. Furthermore, in comparison to the pMDI
application without a spacer a reduced mouth-throat deposition is applicable to
all pMDI spacer combinations. However, some new pMDI release the aerosol in a
quality that may not necessarily require a spacer to avoid a high drug deposition
in the mouth-throat area as the aerosol quality will not be greatly improved with
a spacer. The delivered mass of the active ingredient as well as the aerosol
quality released from a spacer vary substantially with the use of different
spacers. A change of spacer while using the same dose inhaler can maximally
result in a doubling or halving of the quantity of the active ingredient applied.
These facts are nowadays considered by the European regulatory agency. Conclusion
If a spacer application is intended for pMDIs that were developed and approved
after 2009, the correspondent SMP (Summary of Product Characteristics) should at
least make one specific recommendation for a spacer that should be based upon
relevant in vitro data or additional in vivo data. If a different spacer than the
recommended one is used, the effectively applied dose cannot be correctly
anticipated. This should be considered when choosing a spacer.
PMID- 28701015
TI - ?
PMID- 28701016
TI - Tolerance Induction of Horse Allergy by Horse Contact with Curly Horses.
AB - A horse allergic rider completed 60 riding lessons on Curly Horses within six
months. This rider has become clinically tolerant to normal horse breeds within
this time. This case may indicate that riding and brushing ABCR Curly Horses
after 60 riding hours facilitates tolerance induction. Our data indicate that
this could be a valid alternative to the common recommendation to strictly avoid
horse riding.
PMID- 28701017
TI - High Level of Progesteron Receptor Membrane Component 1 (PGRMC 1) in Tissue of
Breast Cancer Patients is Associated with Worse Response to Anthracycline-Based
Neoadjuvant Therapy.
AB - PGRMC1 is known to be highly expressed in breast cancer tissue and is associated
with chemoresistance in breast cancer cells. However, its role in breast cancer
signaling is not fully understood yet. In the present study, the expression
status of PGRMC1 and its phosphorylated version (pPGRMC1) in breast cancer tissue
and surrounding stroma before and after neoadjuvant therapy was examined to find
a possible association to therapy response. Tissue biopsies of 69 breast cancer
patients were analyzed by immunohistochemistry for expression levels of PGRMC1
and pPGRMC1. Expression status of PGRMC1 and pPGRMC1 in tumor tissue was compared
with expression status of progesterone receptor (PR), estrogen receptor alpha
(ERalpha), total estrogen receptor beta (ERbeta), ERbeta1, ERbeta2, the
proliferation marker Ki-67, and human epidermal growth factor receptor 2
(HER2/neu). Correlations were calculated for expression of PGRMC1 and pPGRMC1
before and after neoadjuvant-therapy. PGRMC1 and pPGRMC1 were highly abundant in
every breast cancer tissue sample. Considerably lower signals were detected in
surrounding tissue. Further, PGRMC1 and pPGRMC1 abundance was found to correlate
with ERbeta expression. A lower level of pPGRMC1 could be found in post-therapy
surgical specimens compared to specimens before treatment. Interestingly,
patients with high PGRMC1 tumor levels showed worse response to anthracycline
based therapy as patients with lower PGRMC1 levels. These new findings
demonstrate that PGRMC1 might play an important role in progression and therapy
resistance of human breast tumors and could offer an interesting target for
anticancer therapy.
PMID- 28701018
TI - Bioactive Triterpenoids from the Leaves and Twigs of Lithocarpus litseifolius and
L. corneus.
AB - Phytochemical investigation of the leaves and twigs of Lithocarpus litseifolius
and Lithocarpus corneus resulted in the isolation of four new triterpenoids (1:
4: ), three triterpenoids (5: -7: ) isolated from a natural source for the first
time, and six known compounds (8: -13: ). In addition, four known triterpenoids
(14: -17: ) were isolated from L. corneus. Compound 1: is a 3,4-seco-lupane-type
triterpenoid, and compounds 2: -4: are lupane-type triterpenoids in different
oxidation states. The structures of all isolated compounds were identified by
spectroscopic methods, especially NMR and mass spectrometry data. The absolute
configuration of 2: and 3: was confirmed by X-ray single crystallographic
analysis. The anti-inflammatory activities of 1: -17: and anti-HIV activities of
2: -17: were evaluated. Among them, 3-epi-betulinic acid (8: ) showed a strong
anti-HIV activity comparable to abacavir, a drug used for treating HIV/AIDS. 3,4
seco-4(23),20(29)-lupadiene-3,28-dioic acid (5: ) exhibited potent inhibition of
superoxide-anion generation with 86.9 +/- 2.8% inhibition at 1 uM.
PMID- 28701019
TI - Decontamination of Mikania glomerata Leaves by Gamma Irradiation: Coumarin
Determination by HPLC-DAD, Microbiological Control and Genotoxicological Studies.
AB - Gamma irradiation as a decontaminating physical agent could be an important tool
in the production chain of herbal medicines by improving the microbiological
quality of raw materials and the safety of final products. This study was
undertaken to investigate the genotoxic potential and eventual chemical
modifications of a batch of Mikania glomerata raw material decontaminated by
different doses of gamma irradiation (2.0, 3.5, and 5.0 kGy), using a cesium-137
source. DNA damage was assessed in vitro by agarose gel electrophoresis in regard
to double-chain breaks of plasmid pUC 9.1 DNA and in vivo by micronucleus test in
bone marrow cells of Wistar rats. Cytotoxicity in bone marrows was assessed by
scoring polychromatic and normochromatic erythrocytes ratio. An HPLC-DAD method
was adapted and validated for the enhancement of coumarin selectivity from the
other matrix constituents. The microbial load was satisfactorily reduced, leading
to sterilization at the highest dose. Genotoxic and cytotoxic effects were not
increased in the in vitro and in vivo models. The concentration of coumarin and
the chromatographic profiles of the hydroalcoholic plant extracts (ethanol 70%
v/v) were not modified after such process. Therefore, this work suggests that
gamma irradiation of M. glomerata raw material is suitable and safe for
microbiological control purposes at the employed doses.
PMID- 28701020
TI - The Identification of Araliaceae Species by ITS2 Genetic Barcoding and Pollen
Morphology.
AB - The genetic barcode ITS2 (ITS: internal transcribed spacer) and pollen morphology
were used for the identification of the pharmacologically valuable wild
Araliaceae species Panax ginseng, Oplopanax elatus, Aralia elata, Aralia
continentalis, Eleutherococcus senticosus, and Eleutherococcus sessiliflorus
inhabiting the natural forests of Primorye, Russia. The ITS2 locus successfully
identified all six species, which supports the use of ITS2 as a standard barcode
for medicinal plants. However, the ITS2 locus was insufficient for intra-specific
discrimination in these species, neither within Primorye nor from other world
representatives within GenBank. Araliaceae pollen was confirmed to undergo size
reducing metamorphosis. The final morphotypes were species-specific for each of
the six species but could not discriminate intra-species geographic localities
within Primorye. The morphologies of the final pollen morphotypes from homologous
species inhabiting other parts of the world are not yet known. Therefore, whether
pollen is applicable for Araliaceae intra-species discrimination between Primorye
and other world localities could not be established. Based on these findings, we
propose that the ITS2 genetic barcode and the final pollen morphotypes are
suitable for the identification of Araliaceae species. However, further studies
will be needed to determine the suitability of genetic and pollen traits for
Araliaceae geographic authentication.
PMID- 28701021
TI - Apple Pomace as Potential Source of Natural Active Compounds.
AB - Apple pomace is a waste product of the apple manufacturing industry that has been
in the focus of life sciences as it represents a low-cost source of fruit-derived
compounds. High fruit consumption is associated with beneficial health effects,
and therefore, apple pomace and its constituents raise therapeutic interest. The
present work reviews (i) the chemical constituents of apple pomace, (ii)
optimized extraction methods of apple pomace compounds, and (iii) biological
activities of apple pomace. Current evidence of apple pomace influence on
digestion and metabolism, cholesterol and triglyceride homeostasis, diabetes, and
sex hormones is summarized. Furthermore, studies regarding its antioxidative,
anti-inflammatory, antiproliferative, antibacterial and antiviral effects are
presented. The review concludes that apple pomace is an underutilized waste
product of the apple industry with the potential of being processed for its
nutritional and pharmaceutical value.
PMID- 28701022
TI - Induction of Labor using Misoprostol in a Tertiary Hospital in the Southeast of
Brazil.
AB - Purpose To assess cases of labor induction with vaginal 25-ug tablets of
misoprostol and maternal outcomes in a tertiary hospital in southeastern Brazil.
Methods This was a retrospective cohort study of 412 pregnant women with
indication for labor induction. Labor induction was performed with vaginal 25-ug
tablets of misoprostol in pregnant women with Bishop scores < 6. Stepwise
regression analysis was used to identify the factors present at the beginning of
induction that could be used as predictors of successful labor induction. Results
A total of 69% of the pregnant women who underwent labor induction progressed to
vaginal delivery, and 31% of the women progressed to cesarean section. One or two
misoprostol tablets were used in 244 patients (59.2%). Of the 412 patients, 197
(47.8%) required oxytocin later on in the labor process, after induction with
misoprostol. The stepwise regression analysis showed that only Bishop scores of 4
and 5 and previous vaginal delivery were independent factors with statistical
significance in the prediction of successful vaginal labor induction (beta =
0.23, p < 0.001, for a Bishop score of 4 and 5, and beta = 0.22, p < 0.001, for
previous vaginal delivery). Conclusion Higher Bishop scores and previous vaginal
delivery were the best predictors of successful labor induction with vaginal 25
ug tablets of misoprostol.
PMID- 28701023
TI - Preterm Preeclampsia and Timing of Delivery: A Systematic Literature Review.
AB - Introduction Preeclampsia, a multifactorial disease with pathophysiology not yet
fully understood, is a major cause of maternal and perinatal morbidity and
mortality, especially when preterm. The diagnosis is performed when there is an
association between arterial hypertension and proteinuria or evidence of
severity. There are unanswered questions in the literature considering the timing
of delivery once preterm preeclampsia has been diagnosed, given the risk of
developing maternal complications versus the risk of adverse perinatal outcomes
associated with prematurity. The objective of this systematic review is to
determine the best timing of delivery for women diagnosed with preeclampsia
before 37 weeks of gestation. Methods Systematic literature review, performed in
the PubMed database, using the terms preeclampsia, parturition and timing of
delivery to look for studies conducted between 2014 and 2017. Studies that
compared the maternal and perinatal outcomes of women who underwent immediate
delivery or delayed delivery, in the absence of evidence of severe preeclampsia,
were selected. Results A total of 629 studies were initially retrieved. After
reading the titles, 78 were selected, and their abstracts, evaluated; 16 were
then evaluated in full and, in the end, 6 studies (2 randomized clinical trials
and 4 observational studies) met the inclusion criteria. The results were
presented according to gestational age range (< 34 weeks and between 34 and 37
weeks) and by maternal and perinatal outcomes, according to the timing of
delivery, considering immediate delivery or expectant management. Before 34
weeks, the maternal outcomes were similar, but the perinatal outcomes were
significantly worse when immediate delivery occurred. Between 34 and 37 weeks,
the progression to severe maternal disease was slightly higher among women
undergoing expectant management, however, with better perinatal outcomes.
Conclusions When there is no evidence of severe preeclampsia or impaired fetal
well-being, especially before 34 weeks, the pregnancy should be carefully
surveilled, and the delivery, postponed, aiming at improving the perinatal
outcomes. Between 34 and 37 weeks, the decision on the timing of delivery should
be shared with the pregnant woman and her family, after providing information
regarding the risks of adverse outcomes associated with preeclampsia and
prematurity.
PMID- 28701024
TI - Management of Axillary Web Syndrome after Breast Cancer: Evidence-Based Practice.
AB - Axillary web syndrome is characterized as a physical-functional complication that
impacts the quality of life of women who have undergone treatment for breast
cancer. The present study aims to verify the physiotherapy treatment available
for axillary web syndrome after surgery for breast cancer in the context of
evidence-based practice. The selection criteria included papers discussing
treatment protocols used for axillary web syndrome after treatment for breast
cancer. The search was performed in the MEDLINE, Scopus, PEDro and LILACS
databases using the terms axillary web syndrome, lymphadenectomy and breast
cancer, focusing on women with a previous diagnosis of breast cancer who
underwent surgery with lymphadenectomy as part of their treatment. From the 262
studies found, 4 articles that used physiotherapy treatment were selected. The
physiotherapy treatment was based on lymphatic drainage, tissue mobilization,
stretching and strengthening. The four selected articles had the same outcome:
improvement in arm pain and shoulder function and/or dissipation of the axillary
cord. Although axillary web syndrome seems to be as frequent and detrimental as
other morbidities after cancer treatment, there are few studies on this subject.
The publications are even scarcer when considering studies with an interventional
approach. Randomized controlled trials are necessary to support the
rehabilitation resources for axillary web syndrome.
PMID- 28701025
TI - Epidemiology of hepatic encephalopathy in german hospitals - the EpHE study.
AB - Background Hepatic encephalopathy (HE) is a serious complication of liver
cirrhosis. The proportion of patients with liver cirrhosis attending German
hospitals suffering from HE is unknown. Methods In the first part of the study,
data of 14 community hospitals and 5 university hospitals covering the years 2010
and 2011 were analyzed retrospectively for the DRG codes of liver cirrhosis and
hepatic encephalopathy. In the second prospective part of the multicenter
observational study, all patients with liver cirrhosis attending the departments
of gastroenterology of 16 participating community hospitals within a study period
of 3 months were included and screened for HE clinically according to the West
Haven criteria (grades 1 - 4). Results A diagnosis of liver cirrhosis has been
coded in 6366 cases in 2010 and in 7279 cases in 2011. In the vast majority of
hospitals, less than 20 % of these cases had an additional DRG code for HE. Two
hundred seventy-eight patients with liver cirrhosis were included into the
prospective study. A clinically detectable HE was present in 36 % of the patients
(n = 99). The majority was classified as West Haven 1 (n = 59, 59.6 %). Of the
patients without clinical sings of HE, 48 % (n = 134) showed a pathological NCT.
Conclusion Our data suggest that HE is underdiagnosed in German hospitals. Since
treatment of HE may improve the prognosis of the patients as well as their
quality of life, hospitalized patients with liver cirrhosis should be routinely
screened for HE.
PMID- 28701026
TI - [Ultrasound in oncology, current perspectives].
AB - In tumor diagnostics, especially in the staging diagnostic of tumor patients,
ultrasound is predominantly an additive method in the age of modern imaging
(CT/MRT/PET-CT), because of the limitation by interobserver variability and poor
sound conditions. The aim of this thesis is to elaborate specific oncological
questions on the sonography and to describe the requirements for sonography and
the importance of the method in the diagnosis of tumor diseases in the age of CT,
MRT and PET-CT. In general, the requirements on the sonography must be
differentiated between primary diagnosis, staging diagnostic, treatment response,
and tumor aftercare. This paper will present these in the context of the current
guidelines of the European Federation of Societies for Ultrasound in Medicine and
Biology (EFSUMB) and the Working Community of the Scientific Medical Societies as
well as the requirements in clinical practice.
PMID- 28701027
TI - Children reading spoken words: interactions between vocabulary and orthographic
expectancy.
AB - There is an established association between children's oral vocabulary and their
word reading but its basis is not well understood. Here, we present evidence from
eye movements for a novel mechanism underlying this association. Two groups of 18
Grade 4 children received oral vocabulary training on one set of 16 novel words
(e.g., 'nesh', 'coib'), but no training on another set. The words were assigned
spellings that were either predictable from phonology (e.g., nesh) or
unpredictable (e.g., koyb). These were subsequently shown in print, embedded in
sentences. Reading times were shorter for orally familiar than unfamiliar items,
and for words with predictable than unpredictable spellings but, importantly,
there was an interaction between the two: children demonstrated a larger benefit
of oral familiarity for predictable than for unpredictable items. These findings
indicate that children form initial orthographic expectations about spoken words
before first seeing them in print. A video abstract of this article can be viewed
at: https://youtu.be/jvpJwpKMM3E.
PMID- 28701028
TI - Psychological interventions for acute pain after open heart surgery.
AB - BACKGROUND: This is an update of a Cochrane review previously published in 2014.
Acute postoperative pain is one of the most disturbing complaints in open heart
surgery, and is associated with a risk of negative consequences. Several trials
investigated the effects of psychological interventions to reduce acute
postoperative pain and improve the course of physical and psychological recovery
of participants undergoing open heart surgery. OBJECTIVES: To compare the
efficacy of psychological interventions as an adjunct to standard care versus
standard care alone or standard care plus attention control in adults undergoing
open heart surgery for pain, pain medication, psychological distress, mobility,
and time to extubation. SEARCH METHODS: For this update, we searched the Cochrane
Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, Web of Science,
and PsycINFO for eligible studies up to February 2017. We used the 'related
articles' and 'cited by' options of eligible studies to identify additional
relevant studies. We checked lists of references of relevant articles and
previous reviews. We searched the ProQuest Dissertations and Theses Full Text
Database, ClinicalTrials and the WHO International Clinical Trials Registry
Platform to identify any unpublished material or ongoing trials. We also
contacted the authors of primary studies to identify any unpublished material. In
addition, we wrote to all leading heart centres in Germany, Switzerland, and
Austria to check whether they were aware of any ongoing trials. SELECTION
CRITERIA: Randomised controlled trials comparing psychological interventions as
an adjunct to standard care versus standard care alone or standard care plus
attention in adults undergoing open heart surgery. DATA COLLECTION AND ANALYSIS:
Two review authors (SZ and SK) independently assessed trials for eligibility,
estimated the risk of bias and extracted all data. We calculated effect sizes for
each comparison (Hedges' g) and meta-analysed data using a random-effects model.
We assessed the evidence using GRADE and created 'Summary of findings' tables.
MAIN RESULTS: We added six studies to this update. Overall, we included 23
studies (2669 participants).For the majority of outcomes (two-thirds), we could
not perform a meta-analysis since outcomes were not measured, or data were
provided by one trial only.No study reported data on the number of participants
with pain intensity reduction of at least 50% from baseline. Only one study
reported data on the number of participants below 30/100 mm on the Visual
Analogue Scale (VAS) in pain intensity (very low-quality evidence). Psychological
interventions did not reduce pain intensity in the short-term interval (g 0.39,
95% CI -0.18 to 0.96, 2 studies, 104 participants, low-quality evidence), medium
term interval (g -0.02, 95% CI -0.24 to 0.20, 4 studies, 413 participants,
moderate-quality evidence) or in the long-term interval (g 0.05, 95% CI -0.20 to
0.30, 2 studies, 200 participants, moderate-quality evidence).No study reported
data on median time to re-medication or on number of participants re-medicated.
Only two studies provided data on postoperative analgesic use in the short-term
interval, showing that psychological interventions did not reduce the use of
analgesic medication (g 1.18, 95% CI -2.03 to 4.39, 2 studies, 104 participants,
low-quality evidence). Studies revealed that psychological interventions reduced
mental distress in the medium-term (g 0.37, 95% CI 0.13 to 0.60, 13 studies, 1388
participants, moderate-quality evidence) and likewise in the long-term interval
(g 0.32, 95% CI 0.10 to 0.53, 14 studies, 1586 participants, moderate-quality
evidence). Psychological interventions did not improve mobility in the medium
term interval (g 0.23, 95% CI -0.22 to 0.67, 3 studies, 444 participants, low
quality evidence), nor in the long-term interval (g 0.09, 95% CI -0.10 to 0.28, 4
studies, 458 participants, moderate-quality evidence). Only two studies reported
data on time to extubation, indicating that psychological interventions reduced
the time to extubation (g 0.56, 95% CI 0.08 to 1.03, 2 studies, 154 participants,
low-quality evidence).Overall, the very low to moderate quality of the body of
evidence on the efficacy of psychological interventions for acute pain after open
heart surgery cannot be regarded as sufficient to draw robust conclusions.Most
'Risk of bias' assessments were low or unclear. We judged selection bias (random
sequence generation) and attrition bias to be mostly low risk for included
studies. However, we judged the risk of selection bias (allocation concealment),
performance bias, detection bias and reporting bias to be mostly unclear.
AUTHORS' CONCLUSIONS: In line with the conclusions of our previous review, there
is a lack of evidence to support or refute psychological interventions in order
to reduce postoperative pain in participants undergoing open heart surgery. We
found moderate-quality evidence that psychological interventions reduced mental
distress in participants undergoing open heart surgery. Given the small numbers
of studies, it is not possible to draw robust conclusions on the efficacy of
psychological interventions on outcomes such as analgesic use, mobility, and time
to extubation respectively on adverse events or harms of psychological
interventions.
PMID- 28701029
TI - High-risk prescribing in an Irish primary care population: trends and variation.
AB - AIMS: The aims of the present study were to examine the prevalence of high-risk
prescribing (HRP) in community-dwelling adults in Ireland from 2011-2015 using
consensus-validated indicators, factors associated with HRP, and the variation in
HRP between general practitioners (GPs) and in the dispensing of high-risk
prescriptions between pharmacies. METHODS: A repeated cross-sectional national
pharmacy claims database study was conducted. Prescribing indicators were based
on those developed in formal consensus studies and applicable to pharmacy claims
data. Multilevel logistic regression was used to examine factors associated with
HRP and dispensing. RESULTS: There were significant reductions in the rates of
most indicators over time (P < 0.001). A total of 66 022 of 300 906 patients at
risk in 2011 [21.9%, 95% confidence interval (CI) 21.8, 22.1%], and 42 109 of 278
469 in 2015 (15.1%, 95% CI 15.0, 15.3%), received >=1 high-risk prescription (P <
0.001). In 2015, indicators with the highest rates of HRP were prescription of a
nonsteroidal anti-inflammatory drug (NSAID) without gastroprotection in those
>=75 years (37.2% of those on NSAIDs), coprescription of warfarin and an
antiplatelet agent or high-risk antibiotic (19.5% and 16.2% of those on warfarin,
respectively) and prescription of digoxin >=250 MUg day-1 in those >=65 years
(14.0% of those on digoxin). Any HRP increased significantly with age and number
of chronic medications (P < 0.001). a) After controlling for patient variables,
the variation in the rate of HRP between GPs was significant (P < 0.05); and b)
after controlling for patient variables and the prescribing GP, the variation in
the rate of dispensing of high-risk prescriptions between pharmacies was
significant (P < 0.05). CONCLUSIONS: HRP in Ireland has declined over time,
although some indicators persist. The variation between GPs and pharmacies
suggests the potential for improvement in safe medicines use in community care,
particularly in vulnerable older populations.
PMID- 28701030
TI - Crizotinib versus Chemotherapy in Asian Patients with ALK-Positive Advanced Non
small Cell Lung Cancer.
AB - Purpose: Crizotinib has demonstrated superior progression-free survival (PFS) and
objective response rates (ORRs) versus chemotherapy in previously treated and
untreated patients with anaplastic lymphoma kinase (ALK)-positive advanced non
small cell lung cancer (NSCLC). We report the safety and efficacy of crizotinib
in Asian subpopulations of two global phase III trials. Materials and Methods:
This analysis evaluated previously treated and untreated patients in two
randomized, openlabel phase III trials of crizotinib versus chemotherapy in ALK
positive advanced NSCLC in second-line (PROFILE 1007) and first-line settings
(PROFILE 1014). Efficacy and safety were analyzed by race in the intention-to
treat and "as-treated" populations for efficacy and safety endpoints,
respectively. Results: In previously treated (n=157) and untreated (n=157) Asian
patients, PFS was statistically significantly longer with crizotinib versus
chemotherapy (hazard ratio for PFS, 0.526; 95% confidence interval, 0.363 to
0.762; p < 0.001 and hazard ratio, 0.442; 95% confidence interval, 0.302 to
0.648; p < 0.001, respectively). Similar antitumor activity was seen in the non
Asian and overall populations. ORRs were statistically significantly higher with
crizotinib versus chemotherapy in both Asian and non-Asian previously treated and
untreated patients (p < 0.05). The most common treatment-emergent adverse events
(any grade)with crizotinib were vision disorder, diarrhea, and nausea, which were
observed at a comparable incidence across Asian and non-Asian populations,
irrespective of previous treatment status. Most adverse events were mild to
moderate in severity. Conclusion: These data, currently the only analysis showing
Asian and non-Asian populations in the same study, support the efficacy and
safety of crizotinib in Asian patients with previously treated or untreated ALK
positive advanced NSCLC.
PMID- 28701031
TI - Patient's Cognitive Function and Attitudes towards Family Involvement in Cancer
Treatment Decision Making: A Patient-Family Caregiver Dyadic Analysis.
AB - Purpose: Older patient populations commonly have cognitive impairment, which
might impact decisional capacity. We examined patients and family caregivers
preferences for family involvement in treatment decision making assuming
different level of cognitive impairment, and sought to explore the factors
associated with the preferences and the degree to which patients and family
members agree on preferences. Materials and Methods: A total of 358 elderly
cancer patient and caregiver dyads were recruited from the 11 cancer centers in
Korea andwere asked to express their preferences forfamily involvement in
treatment decision making using hypothetical scenarios with three different
levels of cognitive status (intact, mild impairment, and severe impairment).
Results: Both patients and family caregivers preferred greater family dominance
in treatment decision makingwith the increasing the level of cognitive impairment
(39.7%, 60.9%, and 86.6% for patients and 45.0%, 66.2%, and 89.7% for caregivers
in each scenarios). Patient and family caregiver concordance in decisional
control preference was small for all three scenarios (weighted kappa=0.32,
kappa=0.26, and kappa=0.36, respectively). Higher patient education was
associated with preference for patient dominance in treatment decision in
conditions of both mild and severe cognitive impairment. The association of
higher patient education and patient-caregiver preference concordance was
positive with intact cognition, while it was negative with severe cognitive
impairment. Conclusion: Decision control preferences were affected by
hypothesized cognitive status of the patients. Findings from our study would be
helpful to develop effective strategy for optimizing family involvement in cancer
treatment decision in the context of deteriorating cognitive function of the
patients.
PMID- 28701033
TI - Ionic Strength Differentially Affects the Bioavailability of Neutral and
Negatively Charged Inorganic Hg Complexes.
AB - Mercury (Hg) bioavailability to bacteria in marine systems is the first step
toward its bioamplification in food webs. These systems exhibit high salinity and
ionic strength that will both alter Hg speciation and properties of the bacteria
cell walls. The role of Hg speciation on Hg bioavailability in marine systems has
not been teased apart from that of ionic strength on cell wall properties,
however. We developed and optimized a whole-cell Hg bioreporter capable of
functioning under aerobic and anaerobic conditions and exhibiting no
physiological limitations of signal production to changes in ionic strength. We
show that ionic strength controls the bioavailability of Hg species, regardless
of their charge, possibly by altering properties of the bacterial cell wall. The
unexpected anaerobic bioavailability of negatively charged halocomplexes may help
explain Hg methylation in marine systems such as the oxygen-deficient zone in the
oceanic water column, sea ice or polar snow.
PMID- 28701032
TI - BCL2 Regulation according to Molecular Subtype of Breast Cancer by Analysis of
The Cancer Genome Atlas Database.
AB - Purpose: We investigated B-cell lymphoma 2 (BCL2) regulation across DNA, RNA,
protein, and methylation status according to molecular subtype of breast cancer
using The Cancer Genome Atlas (TCGA) database. Materials and Methods: We analyzed
clinical and biological data on 1,096 breast cancers from the TCGA database.
Biological data included reverse phase protein array (RPPA), mRNA sequencing
(mRNA-seq), mRNA microarray, methylation, copy number alteration linear, copy
number alteration nonlinear, and mutation data. Results: The luminal A and
luminal B subtypes showed upregulated expression of RPPA and mRNAseq and
hypomethylation compared to the human epidermal growth factor receptor 2 (HER2)
and triple-negative subtypes (all p < 0.001). No mutations were found in any
subjects. High mRNA-seq and high RPPA were strongly associated with positive
estrogen receptor, positive progesterone receptor (all p < 0.001), and negative
HER2 (p < 0.001 and p=0.002, respectively). Correlation analysis revealed a
strong positive correlation between protein and mRNA levels and a strong negative
correlation between methylation and protein and mRNA levels (all p < 0.001). The
high BCL2 group showed superior overall survival compared to the low BCL2 group
(p=0.006). Conclusion: The regulation of BCL2 was mainly associated with
methylation across the molecular subtypes of breast cancer, and luminal A and
luminal B subtypes showed upregulated expression of BCL2 protein, mRNA, and
hypomethylation. Although copy number alteration may have played a minor role,
mutation status was not related to BCL2 regulation. Upregulation of BCL2 was
associated with superior prognosis than downregulation of BCL2.
PMID- 28701034
TI - A-Site Cation Effect on Growth Thermodynamics and Photoconductive Properties in
Ultrapure Lead Iodine Perovskite Monocrystalline Wires.
AB - Among the various building blocks beyond polycrystalline thin films, perovskite
wires have attracted extensive attention for potential applications including
nanolasers, waveguides, field-effect transistors, and more. In this work,
millimeter-scale lead iodine-based perovskite wires employing various A-site
substitutions, namely, Cs, methylammonium (MA), and formamidinium (FA), have been
synthesized via a new type solution method with nearly 100% yield. All of the
three millimeter scale perovskite wires (MPWs) compositions exhibit relatively
high quality, and CsPbI3 is proven to be monocrystalline along its entire length.
Furthermore, the growth thermodynamics of the APbI3 MPWs with respect to A-site
cation effect were studied thoroughly by various characterization techniques.
Finally, single MPW photodetectors have been fabricated utilizing the APbI3 MPWs
for studying the photoconductive properties, which show different sensitivities
under illumination. This systematic synthesis method of solution-processed APbI3
(Cs, MA, and FA) MPWs reveals a wide spectrum of additives with different
coordination capability that mediates perovskite materials growth. It proved to
serve as a new parameter that further aids in the rational process of the
polycrystalline organic/inorganic hybrids materials. These MPWs also have the
potential to open up new opportunities for integrated nanoelectronics ranging
from the nanometer through millimeter length scales.
PMID- 28701035
TI - Predictably Ordered Open Hydrogen-Bonded Networks Built from Indeno[1,2
b]fluorenes.
AB - Predictably ordered materials can be constructed by a modular strategy in which
properly designed molecular components are positioned in space by reliable
interactions. In principle, this approach can be used to control the arrangement
of adjacent systems of pi-conjugation, thereby creating molecular materials with
valuable optoelectronic properties. To explore this possibility, we have
synthesized compounds in which 2,4-diamino-1,3,5-triazinyl groups are attached to
derivatives of 6,12-dihydroindeno[1,2-b]fluorene to produce molecules with well
defined cruciform topologies, extended pi-conjugated aromatic cores, and an
ability to form multiple hydrogen bonds. These compounds crystallize to form
robust open hydrogen-bonded networks with parallel indenofluorenyl cores,
significant volume (64-70%) available for accommodating guests, and
characteristic luminescence. Our results will help permit the rational design of
complex new molecular materials in which multiple optoelectronically active
components are arranged in productive ways.
PMID- 28701036
TI - Characterization of Surface-Active Biofilm Protein BslA in Self-Assembling
Langmuir Monolayer at the Air-Water Interface.
AB - Biofilm is an extracellular matrix of bacteria and serves as a protective shield
of bacterial communities. It is crucial for microbial growth and one of the
leading causes of human chronic infections as well. However, the structures and
molecular mechanism of biofilm formation remain largely unknown. Here, we
examined a protein, BslA, expressed in the biofilms of Bacillus subtilis. We
characterized the Langmuir monolayers of BslA at the air/water interface. Using
techniques in surface chemistry and spectroscopy, we found that BslA forms a
stable and robust Langmuir monolayer at the air/water interface. Our results show
that the BslA Langmuir monolayer underwent two-stage elasticity in the solid
state phase upon mechanical compression: one is possibly due to the
intermolecular interaction and the other is likely due to both the intermolecular
compulsion and the intramolecular distortion. The Langmuir monolayer of BslA
shows abrupt changes in rigidities and elasticities at ~25 mN/m. This surface
pressure is close to the one at which BlsA saturates the air/water interface as a
self-assembled film without mechanical compression, corresponding to a mean
molecular area of ~700 A2 per molecule. Based on the results of surface UV
visible spectroscopy and infrared reflective-absorption spectroscopy, we propose
that the BslA Langmuir monolayer carries intermolecular elasticity before ~25
mN/m and both intermolecular and intramolecular elasticity after ~25 mN/m. These
results provide valuable insights into the understanding of biofilm-associated
protein under high mechanical force, shedding light on further investigation of
biofilm structure and functionalities.
PMID- 28701037
TI - Using Polyethylene Passive Samplers To Study the Partitioning and Fluxes of
Polybrominated Diphenyl Ethers in an Urban River.
AB - In the aquatic environment, the behavior of hydrophobic organic contaminants
(HOCs), such as polybrominated diphenyl ethers (PBDEs), depends on the congeners'
physicochemical properties, environmental conditions and the presence of
competing natural sorbents, including particulate and dissolved organic carbon
(DOC) and black carbon (BC). Although BC is known as an important sedimentary
sorbent for HOCs, its affinity for PBDEs has been poorly constrained. To better
understand the biogeochemical controls on PBDEs, 12 PBDE congeners were measured
in air, water, sediment and porewater of the lower Passaic River. BDE-47 and BDE
99 dominated in all media. In sediments and water, the dual OC + BC approach
better predicted PBDE partitioning compared to the simple OC isotherm. Field
derived KBC values for PBDEs were inversely correlated with aqueous solubility
[log KBC sediments(water) = -log Cwsat * 0.95 (1.2) + 0.36 (-0.69)]; they
reflected near background to highly contaminated regions across the Passaic
River. In the water column, PBDEs appeared at equilibrium partitioning between
particles and colloids: OC + BC were responsible for the sorption of 65% of
PBDEs, followed by colloids (30%); only 5% of PDBEs were truly dissolved.
Calculated sediment-water diffusive fluxes greatly overwhelmed the atmospheric
depositional flux to the river.
PMID- 28701038
TI - Micellear Gold Nanoparticles as Delivery Vehicles for Dual Tyrosine Kinase
Inhibitor ZD6474 for Metastatic Breast Cancer Treatment.
AB - The therapeutic index of poorly water-soluble drugs is often hampered due to poor
pharmacokinetics, reduced blood retention, and lack of effective drug
concentrations in the tumor region. In order to overcome these issues, drugs are
often delivered by use of delivery vehicles to provide an enhanced therapeutic
index. Gold nanoparticles synthesized in micellar networks of amphiphilic block
copolymer (AuNM) provide an efficient nanocarrier for tissue- and site-specific
drug delivery owing to their low cytotoxicity and immunogenicity. AuNM is formed
by exploiting the properties of both inorganic Au material and an amphiphilic
polymer of poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene
glycol) (PEG-PPG-PEG). We further functionalized AuNM with the FDA-approved dual
tyrosine kinase inhibitor ZD6474 and studied the physicochemical properties of
the conjugate ZD6474-AuNM. Both AuNM and ZD6474-AuNM, with a diameter of ~70 nm,
were very stable at physiological pH. Conversely, at an acidic pH of 5.2, a slow
sustained-release profile of ZD6474 was evident from AuNM, which could provide a
method of facilitating release of the drug in an acidic tumor environment. In
vitro, in triple-negative breast cancer cells, ZD6474-AuNM inhibited tumor cell
proliferation, migration, and invasion and induced apoptosis. There was no
detectable lysis of red blood cells observed when they were treated with AuNM and
ZD6474-AuNM, confirming hemocompatibility. To reinforce the possibility of AuNM
serving as a delivery vehicle, AuNM was conjugated with the IR680 dye for
tracking, and this conjugate was systemically delivered in female nude mice
bearing MDA-MB-231 human breast cancer xenografts. Fluorescence signal was
retained in the tumor region in a temporal manner as compared to other organs,
indicating passive retention of AuNM in the tumor locale. Moreover, delivery of
ZD6474-AuNM in nude mice bearing MDA-MB-231 xenografts led to decreased tumor
size as compared to the control group. The promising safety, targeting, and
therapeutic results of systemic delivery of ZD6474 by AuNM provide an attractive
alternative method for treating patients with metastatic breast cancer.
PMID- 28701039
TI - Aminofutalosine Synthase: Evidence for Captodative and Aryl Radical Intermediates
Using beta-Scission and SRN1 Trapping Reactions.
AB - Aminofutalosine synthase (MqnE) is a radical SAM enzyme involved in the
menaquinone biosynthetic pathway. In this communication, we propose a novel
mechanism for this reaction involving the addition of the adenosyl radical to the
substrate double bond to form a captodative radical followed by rearrangement and
decarboxylation to form an aryl radical anion which is then oxidized by the [4Fe
4S]+2 cluster. Consistent with this proposal, we describe the trapping of the
captodative radical and the aryl radical anion using radical triggered C-Br
fragmentation reactions. We also describe the trapping of the captodative radical
by replacing the vinylic carboxylic acid with an amide.
PMID- 28701040
TI - In Situ Production of Graphene-Fiber Hybrid Structures.
AB - We report a scalable method to obtain a new material where large graphene sheets
form webs linking carbon fibers. Film-fiber hybrid nonwoven mats are formed
during fiber processing and converted to carbon structures after a simple thermal
treatment. This contrasts with multistep methods that attempt to mix previously
prepared graphene and fibers, or require complicated and costly processes for
deposition of graphene over carbon fibers. The developed graphene-fiber hybrid
structures have seamless connections between graphene and fibers, and in fact the
graphene "veils" extend directly from one fiber into another forming a continuous
surface. The graphene-fiber hybrid structures are produced in situ from aqueous
poly(vinyl alcohol) solutions. The solutions were subjected to centrifugal
spinning to produce fine nanofiber mats. The addition of salt to the polymer
solution stimulated a capillarity effect that promoted the formation of thin
veils, which become graphene sheets upon dehydration by sulfuric acid vapor
followed by carbonization (at relatively low temperatures, below 800 degrees C).
These veils extend over several micrometers within the pores of the fiber
network, and consist of crystalline graphene layers that cross-link the fibers to
form a highly interconnected hybrid network. The surface area and pore diameter
of the hybrid structures were measured to be 521 m2g-1 and 10 nm, respectively.
The resulting structure shows high electrical conductivity, 550 S/m, and
promising shielding of electromagnetic interference, making it an attractive
system for a broad range of electronic applications.
PMID- 28701041
TI - Stereoelectronic Interactions as a Probe for the Existence of the Intramolecular
alpha-Effect.
AB - The first systematic study of the intramolecular alpha-effect, both in the stable
ground-state structures and in the high-energy intermediates, was accomplished
using the anomeric effect as an internal stereoelectronic probe. Contrary to the
expectations based on the simple orbital mixing model, the lone pairs in a pair
of neutral directly connected heteroatoms are not raised in energy to become
stronger donors toward adjacent sigma- and pi-acceptors. Instead, the key n(X-Y)
>sigma*C-F interactions (X,Y = O,N) in the "alpha-systems" (both acyclic and
constrained within a heterocyclohexane frame) are weaker than nX->sigma*C-F
interactions in "normal" systems. Surprisingly, polar solvent effects increase
the apparent magnitude of alpha-effect as measured via increase in the anomeric
stabilization. This behavior is opposite to the solvent dependence of normal
systems where the anomeric effect is severely weakened by polar solvents. This
contrasting behavior reflects the different balance of electrostatic and
conjugative interactions in the two types of anomeric systems: the alpha-systems
suffer less from the unfavorable orientation of bond dipoles in the equatorial
conformer, a destabilizing electrostatic effect that is shielded by the polar
environments. A weak alpha-effect is brought to life when the buttressing alpha
heteroatom bears a negative charge. However, electrostatic components mask the
role of stabilizing orbital interactions. In contrast, the increased electron
demand in carbocations and related electron-deficient TS- like structures does
not lead to activation of the alpha-effect. As a consequence, we observed that
ethers are better radical- and cation-stabilizing groups than peroxides. The
latter finding should have significant implications for understanding the
mechanistic complexity associated with the interaction of carbonyl compounds with
hydroperoxides and H2O2 in acidic media, as such reactions involve alpha-cationic
intermediates.
PMID- 28701042
TI - Comparison of Protein Extracts from Various Unicellular Green Sources.
AB - Photosynthetic unicellular organisms are considered as promising alternative
protein sources. The aim of this study is to understand the extent to which these
green sources differ with respect to their gross composition and how these
differences affect the final protein isolate. Using mild isolation techniques,
proteins were extracted and isolated from four different unicellular sources
(Arthrospira (spirulina) maxima, Nannochloropsis gaditana, Tetraselmis
impellucida, and Scenedesmus dimorphus). Despite differences in protein contents
of the sources (27-62% w/w) and in protein extractability (17-74% w/w), final
protein isolates were obtained that had similar protein contents (62-77% w/w) and
protein yields (3-9% w/w). Protein solubility as a function of pH was different
between the sources and in ionic strength dependency, especially at pH < 4.0.
Overall, the characterization and extraction protocol used allows a relatively
fast and well-described isolation of purified proteins from novel protein
sources.
PMID- 28701043
TI - In-Situ X-ray Tomography Study of Cement Exposed to CO2 Saturated Brine.
AB - For successful CO2 storage in underground reservoirs, the potential problem of
CO2 leakage needs to be addressed. A profoundly improved understanding of the
behavior of fractured cement under realistic subsurface conditions including
elevated temperature, high pressure and the presence of CO2 saturated brine is
required. Here, we report in situ X-ray micro computed tomography (MU-CT) studies
visualizing the microstructural changes upon exposure of cured Portland cement
with an artificially engineered leakage path (cavity) to CO2 saturated brine at
high pressure. Carbonation of the bulk cement, self-healing of the leakage path
in the cement specimen, and leaching of CaCO3 were thus directly observed. The
precipitation of CaCO3, which is of key importance as a possible healing
mechanism of fractured cement, was found to be enhanced in confined regions
having limited access to CO2. For the first time, the growth kinetics of CaCO3
under more realistic well conditions have thus been estimated quantitatively.
Combining the MU-CT observations with scanning electron microscopy resulted in a
detailed understanding of the processes involved in the carbonation of cement.
PMID- 28701044
TI - "New Physical Chemistry Insight" in Experimental Bio-Physical Chemistry.
PMID- 28701045
TI - Investigating Chemical Composition and Indications of Hydrosol Soft Drinks
(Aromatic Waters) Used in Persian Folk Medicine for Women's Hormonal and
Reproductive Health Conditions.
AB - Hydrosol soft drinks in Persian nutrition culture are produced as side products
of the essential oil industry to be used as safe remedies for treatment of some
ailments. This study investigated hydrosols for women's hormonal health
conditions. Detailed information was gathered by questionnaires. Chemical
constituents of these mono- or poly-herbal hydrosols were identified after
liquid/liquid extraction and gas chromatography-mass spectrometry. Hierarchical
cluster and K-means analysis (SPSS software) were used to find their relevance. A
literature survey was also performed. In most cases, thymol, carvacrol, and
carvone were the major constituents except for dill, white horehound, willow,
Moderr, and yarrow hydrosols, whose their major components were dill ether,
menthol, phenethyl alcohol, linalool, or camphor. Based on clustering methods,
some similarities could be found in their constituents with some exceptions. None
of them have been studied scientifically before. These investigations may lead to
the development of some functional drinks or even new lead components.
PMID- 28701046
TI - A Review of the Antioxidant Activity of Celery ( Apium graveolens L).
AB - Plants are an important source of natural active products that are different,
based on mechanism and biological properties. Celery ( Apium graveolens L) is a
plant from the apiaceae family and phenolic and antioxidant compounds of this
plant have been studied by several scientists. The aim of this study was to
review systematically the antioxidant activity of celery. Required articles were
searched from databases such as Science Direct, PubMed, Scopus, and Springer.
Keywords used in this study were Apium graveolens L, celery, antioxidant, free
radical, leaf, and seed. Out of 980 collected articles (published in the period
1997-2015), 9 studies finally met the inclusion criteria and were considered.
Celery, because of compounds such as caffeic acid, p-coumaric acid, ferulic acid,
apigenin, luteolin, tannin, saponin, and kaempferol, has powerful antioxidant
characteristics, to remove free radicals. It is clear that celery, with different
compounds and diverse concentration can have varied healing effects. It is
suggested that the next studies concentrate on other therapeutic and industrial
attributes of celery.
PMID- 28701047
TI - Heart rate is a useful marker of adherence to beta-blocker treatment in
hypertension.
AB - OBJECTIVES: Suboptimal medication adherence is common among patients with
hypertension. Measurements of plasma or urinary levels of antihypertensive drugs
are useful, but not widely available. The aim of our study was to investigate the
relation of patients' heart rates to their serum beta-blocker levels. METHODS: We
correlated 220 measurements of serum beta-blocker levels in 106 patients with
apparently resistant hypertension to their corresponding office heart rate. A
significant proportion, 44.6% of patients, were non-adherent to beta-blocker
treatment according to serum level measurement. Non-adherent patients had
significantly higher heart rates (80.9 vs. 66.6 bpm, p < .001), systolic (157.4
vs. 147.0 mm Hg, p = .002) and diastolic blood pressure (91.1 vs. 87.2 mm Hg, p =
.041) in comparison to adherent patients. RESULTS: Heart rate above 75.5 beats
per minute predicted non-adherence to beta-blocker treatment with a sensitivity
of 62.5%, specificity 86.8% and AUC ROC 0.802 (p < .001). Higher heart rate
cutoff might be applicable for nebivolol but was not determined due to the low
number of patients treated with nebivolol. CONCLUSIONS: We concluded that heart
rate was shown to be a good predictor of non-adherence to beta-blocker treatment,
and might become a quick and easy measure to determine patient adherence in
hypertensive patients.
PMID- 28701048
TI - An overview of nanosomes delivery mechanisms: trafficking, orders, barriers and
cellular effects.
AB - This review traces the journey of nanosomes from administration until
elimination, and discusses various biological barriers. The nanosomes are
imported into the body through different routes and are localized into specified
organ, cell, subcellular locations or organelle compartment. The nanosomes
delivery to a specific destination depends on the surface chemistry, size, shape
and the presence of specific ligands. Endocytosis/exocytosis cycles are involved
in the import and export of the nanosomes. The mononuclear phagocytic system and
ATP-binding cassette are universal checkpoints for nanosomes trafficking. The
gastrointestinal milieu is the checkpoints for orally administered nanosomes. The
mucociliary escalator is a specialized obstacle for inhaled nanosomes. Dermally
applied nanosomes are tackled by Langerhans cells and keratinocytes. The
nanosomes intended for subcellular destinations are mainly intercepted by
lysosomes. Thus, nanosomes intended for biological administration must be
designed to escape various barriers. The nanosomes affect cells function by
alteration of redox status, and calcium signalling, ultimately, they are
exocytosed from the cells.
PMID- 28701049
TI - Insane acquittees and insane convicts: the rationalization of policy in
nineteenth-century Connecticut.
AB - A current situation in Connecticut of whether a violent insane acquittee should
be held in a state prison or psychiatric facility raises difficult issues in
jurisprudence and medical ethics. Overlooked is that the present case of Francis
Anderson reiterates much of the debate over rationalization of policy during the
formative nineteenth century. Contrary to theories of social control and state
absolutism, governance in Connecticut was largely episodic, indecisive and
dilatory over much of the century. The extraordinary urban and industrial
transformation at the end of the Gilded Age finally forced a coherent response in
keeping with longstanding legal and medical perspectives.
PMID- 28701050
TI - Validation performance comparison for finite element models of the human brain.
AB - The objective of this study was to compare the performance of six validated brain
finite element (FE) models to localized brain motion validation data in five
experimental configurations. Model performance was measured using the objective
metric CORA (CORrelation and Analysis), where higher ratings represent better
correlation. The KTH model achieved the highest average CORA rating, and the ABM
received the highest average rating among models robustly validated against five
cadaver impacts in three directions. This technique can be more frequently
employed to build better models and, when associated limitations are well
understood, to compare inter-model performance under similar conditions.
PMID- 28701051
TI - Longitudinal risk factors for suicidal thoughts in depressed and non-depressed
young adolescents.
AB - OBJECTIVE: Evidence regarding the role of risk factors in the longitudinal course
of suicidal ideation among young adolescents is lacking. We aimed to assess the
effects of a range of risk factors, including obesity, academic performance,
child-parent relationship, physical maltreatment, and depressive symptoms, on the
development of suicidal ideation in young adolescents. METHODS: A school cohort
of seventh and eighth graders was followed for 1 year and differences in the risk
factors distributions were examined between depressed and non-depressed
adolescents. We further examined risk factors for newly developed suicidal
ideation and persistent suicidal ideation in the groups of adolescents based on
the presence of suicidal ideation at baseline. RESULTS: A total of 1710 young
adolescents were recruited, among whom 8.2% were categorised as having clinically
significant depression. For depressed adolescents, being obese was associated
with a three-fold increased risk of having suicidal ideation. For non-depressed
adolescents, physical maltreatment, a feeling of not being cared about and sub
threshold depressive symptoms were the risk factors. The latter two remained
robust in predicting newly developed suicidal ideation. CONCLUSION: The current
study may shed light on the differential strategies to address suicidal thoughts
in depressed and non-depressed adolescents. We emphasise the importance of
recognition and management of sub-threshold depressive symptoms and the relevance
of obesity, physical maltreatment and a feeling of not being cared about to
suicide prevention programmes in early adolescence.
PMID- 28701052
TI - 'They accused me of strangling her': epilepsy and violence debate in Croatia at
the end of the nineteenth and the beginning of the twentieth centuries.
AB - Nineteenth-century psychiatry shifted its focus to the brain as the seat of
mental disorders. With a new understanding of mental disorders arose the need to
consult forensic psychiatrists in cases of criminal acts committed by persons
with mental illness. This article focuses on three murders committed by
'epileptics' at the end of the nineteenth and the beginning of the twentieth
centuries in Croatia. An analysis of these cases will help to situate forensic
psychiatry at the turn of the century within the Austro-Hungarian Empire, and
reveal the authority that forensic experts wielded in the courts. We will argue
that Cesare Lombroso's biological theory of crime, as well as the influence of
eugenicists and pharmaceutical companies, shaped the long-standing relationship
between epilepsy and violent behaviour.
PMID- 28701053
TI - MicroRNA-613 inhibits the progression of gastric cancer by targeting CDK9.
AB - MicroRNAs (miRNAs) play an important role in the development and progression of
human malignancy. miR-613, as a tumour suppressor, was reported to decrease in
several tumours. However, the expression levels and role of miR-613 in gastric
cancer remain unknown. In this study, we found that miR-613 was evidently
downregulated in gastric cancer tissue and cell. The functional analysis showed
that miR-613 suppressed cell proliferation and migration in gastric cancer. Next,
the dual-luciferase reporter system supported CDK9 as a direct target gene of miR
613. miR-613 mimics evidently repressed CDK9 expression in gastric cancer cells.
Furthermore, we found that CDK9 in upregulated in gastric cancer and the CDK9
expression levels were inversely correlated with that of miR-613 in gastric
cancer tissues. Overall, the results revealed that miR-613, as a tumour
suppressor, involves in gastric cancer progression and metastasis by targeting
CDK9, implying a novel potential therapeutic target for the treatment of gastric
cancer.
PMID- 28701055
TI - Perspectives of Dutch health professionals regarding auditory processing
disorders; a focus group study.
AB - OBJECTIVE: This study investigated the perspectives of professionals from the
Dutch audiological centres on the definition and care pathways of children with
suspected auditory processing disorders (susAPD). DESIGN: focus group interviews.
STUDY SAMPLE: In total, 45 professionals from 6 disciplines, representing 22
different audiological centres and one ambulatory service, participated in five
parallel focus group interviews. Participants had a variety of experience in
diagnosing and advising children with suspected APD. RESULTS: Qualitative
analysis (open and thematic) identified four themes ("Definition", "Causes",
"Diagnostic Procedures" and "Clinical Reasoning") expressing a variety of
perspectives. Differences in perspectives were mainly affected by two debates:
(1) whether or not APD exists as a pure (auditory) disorder and (2) whether or
not current AP-tests are suitable in diagnosing children with listening
difficulties. They also expressed a need for more guidance from the literature in
their clinical decision making process. CONCLUSIONS: Professionals from the Dutch
audiological centres share a broad perspective on children with APD. The ICF
framework supports this perspective, thereby diminishing the need for a clear
definition. The use of AP-tests should be limited to children where broader
developmental disorders are first ruled out; a possible "pure" APD could then be
diagnosed in a limited number of children.
PMID- 28701054
TI - Diagnostic and treatment workup for IgG4-related disease.
AB - INTRODUCTION: IgG4-Related Disease is a newly recognized condition which is
increasingly diagnosed by practitioners due to improvement in clinical awareness.
Men and women have been found to be affected by this disease in various organs,
more commonly with involvement of the salivary and lacrimal glands as well as
pancreas and liver. Areas covered: The diagnosis and management of this condition
remain challenging as biomarkers and therapies are being investigated. Hallmark
features on histology are still the gold standard for confirmation of diagnosis,
whereas serum IgG4 level has been shown to be neither necessary nor sufficient
for the diagnosis. Glucocorticoids remain the most effective initial management
for this condition while there are limited clinical trials on the effectiveness
of maintenance therapy. Expert commentary: This review serves as an update on
approaches for diagnosis and management of IgG4-RD. Most of the known data in
this field comes from retrospective cohort studies and expert consensus
guidelines but new ongoing prospective studies, clinical trials and better
understanding of the pathogenesis of this condition are promising.
PMID- 28701056
TI - Effects of polyhexamethylene guanidine phosphate on human gingival fibroblasts.
AB - OBJECTIVE: Polyhexamethylene guanidine phosphate (PHMG-P) was compared to
chlorhexidine (CHX) in order to determine potential cytotoxic and immune
modulatory effects on human gingival fibroblasts. MATERIALS AND METHODS:
Cytotoxic effects of PHMG-P and CHX on human gingival fibroblasts were assessed
using cell viability assay at various time points and concentrations. The effects
of PHMG-P and CHX on the secretion of prostaglandin (PG) E2, interleukin (IL)-6,
IL-8 and matrix metalloproteinase (MMP)-1 by non-stimulated or IL-1beta
stimulated fibroblasts were evaluated by enzyme-linked immunosorbent assays.
RESULTS: PHMG-P concentration 0.00009% led to the total loss of fibroblast
viability within 24 h, whereas inhibition of fibroblast viability by CHX occurred
at significantly higher concentrations of 0.0009% (p < .001). Short-term exposure
to 0.005% PHMG-P led to loss of fibroblast viability after 5 min, whilst cells
exposed to 0.005% CHX survived 30 min of treatment (p < .001). IL-1beta
stimulation induced an inflammatory response with a significant increase in the
secretion of PGE2, IL-6, IL-8 and MMP-1. Treatment of IL-1beta stimulated
fibroblasts in combination with PHMG-P or CHX at concentrations of 0.000045 or
0.0.00009% resulted in significantly decreased PGE2, IL-6, IL-8 and MMP-1 levels.
PHMG-P or CHX alone did not affect the baseline secretion of PGE2, IL-6, IL-8 or
MMP-1 by gingival fibroblasts. CONCLUSIONS: Cytotoxic effects on gingival
fibroblasts were triggered by both PHMG-P and CHX at concentrations below those
used in clinical practice. The tested antiseptics did not cause inflammation and
reduced IL-1beta-induced secretion of inflammatory mediators and collagenase by
gingival fibroblasts, which suggests anti-inflammatory properties.
PMID- 28701058
TI - Attitudes and behavioural factors relating to toothbrushing and the use of
fluoride toothpaste among caries-active Swedish adolescents - a questionnaire
study.
AB - OBJECTIVE: The aim of this study was to identify attitudes and behaviour relating
to fluoride toothpaste and toothbrushing habits among caries-active Swedish
adolescents. MATERIALS AND METHODS: This cross-sectional study is based on an
earlier clinical, two-year toothpaste intervention study. At the last
appointment, 206 adolescents (of 211) answered a questionnaire comprising nine
semi-closed questions. RESULTS: The majority (93%) brushed their teeth every day,
while 7% did so only occasionally. Most participants (77%) brushed twice a day,
while 12% brushed just once a day. About half of those brushing just once a day
forgot to brush in the evening. Similarly, more than half of the adolescents
(53%) used 1 cm of toothpaste or less on their toothbrush. Moreover, 49% brushed
for less than 2 min, 41% brushed for 2 min and 10% for more than 2 min. The
majority (73%) rinsed with water after toothbrushing. A difference between boys
and girls was also observed; 87% of the girls brushed twice a day, whereas only
67% of the boys did so and boys more frequently forgot in the evening.
CONCLUSIONS: Attitudes and behaviour relating to fluoride toothpaste and
toothbrushing habits among caries-active Swedish adolescents are still inadequate
after two years of toothpaste intervention. There are several areas where
improvements can be made, such as frequency of brushing, brushing time, amount of
toothpaste and post-brushing procedures. The majority (81%) included 'fresh
breath' as a reason for performing oral hygiene and this aspect can be used by
dental staff in health promotion.
PMID- 28701059
TI - Brucea javanica oil emulsion alleviates cachexia induced by Lewis lung cancer
cells in mice.
AB - This study was conducted to evaluate the efficacy and possible mechanism of
Brucea javanica oil emulsion (BJOE) on cachexia, by observing changes in related
indexes in mice with cachexia and identifying the genes responsible based on gene
chip analysis. In the BJOE treatment group, body weight loss, tumour growth and
metastasis were found obviously inhibited, food and water intake had markedly
increased, and survival time was significantly prolonged, as compared to the
control group. Moreover, the BJOE witnessed improvement in body weight,
prevention of tumour metastasis and overall increase in survival time, as
compared to Indometacin (IND, the positive control medicine). It was also found
that TNF-alpha and IL-6 in serum were significantly lower in both groups of BJOE
and IND, than in the control group (p < .01). Based on the gene expression data,
seven and six hub genes of BJOE and IND groups were found in the potential
prognostic impacts networks, and three common genes comprising of Nmd3, Bcl2 and
Nhp2l1 were screened. Thus, BJOE could reduce tumour growth and effectively
alleviate cancer cachexia, due to inhibition of pro-inflammatory cytokines. Nmd3,
Bcl2, Nhp2l1 may be important drug targets, establishing the role of BJOE in the
treatment of lung cancer induced cachexia.
PMID- 28701057
TI - Treatment of serious complications following endovascular aortic repair for type
B thoracic aortic dissection.
AB - Objective This study aimed to describe treatment of serious complications after
primary thoracic endovascular aortic repair (TEVAR) in type B aortic dissection.
Methods From June 2008 to March 2016, serious complications occurred in 58
patients without Marfan syndrome who received TEVAR for type B aortic dissection.
Results Complications included endoleak, distal true lumen collapse, retrograde
dissection, stroke, stent-graft (SG) migration and mistaken deployment, lower
limb ischaemia, and SG fracture. Treatment included endovascular repair, surgical
procedures, or conservative medication. Forty-six patients recovered from
complications. Twelve patients were not cured. The median follow-up time was 29.5
months (2-61 months). The overall 30-day mortality rate was 1.7% (1/58) and the
total mortality rate following secondary complications was 8.6% (5/58). The
causes of death were stroke and aortic rupture. Conclusion Some treatments need
to be performed after TEVAR because of severe complications. A reduction in these
complications can be achieved by optimal evaluation of patients, selection of
SGs, and specialized endovascular manipulation.
PMID- 28701060
TI - Epidemiological and clinical characteristics of 304 patients with infantile
hypertrophic pyloric stenosis in Anhui Province of East China, 2012-2015.
AB - OBJECTIVE: To analyze the clinical and epidemiological features of patients with
infantile hypertrophic pyloric stenosis (IHPS) so as to provide scientific
evidence for diagnosis and prevention of IHPS. METHODS: We performed a
retrospective study of infants with IHPS diagnosed from 2012 to 2015 at Anhui
Provincial Children's Hospital. Demographic characteristics and clinical data
were collected. RESULTS: Three hundred four patients (264 males and 40 females)
were studied, of which 94.7% were full term and 75.7% were bottle fed or mixed
fed; 16.8% of the patients had other congenital malformations in combination with
IHPS. The proportion of IHPS cases with hyponatremia, hypokalemia, and
hypochloremia was 18.4%, 12.5%, and 53.9%. A negative correlation was found
between duration of disease and serum electrolytes. The mean pyloric muscle
thickness, pyloric length, and diameter were 4.8 +/- 0.7 mm, 19.4 +/- 2.5 mm, and
13.3 +/- 1.8 mm, respectively. There were significant differences in muscle
thickness, pyloric length, and diameter between short (<=14 d) and long (>14 d)
durations of disease. All patients underwent pyloromyotomy, and postoperative
recovery was good. CONCLUSIONS: IHPS occurs mainly in male, full-term, bottle-fed
or mixed-fed infants. Patients with long duration of disease were more likely to
develop electrolyte disorder and thicker muscle layer. More attention should be
paid to early discovery and diagnosis, which will help to improve the curative
effect and prognosis of IHPS.
PMID- 28701061
TI - Subthalamic nucleus and globus pallidus internus stimulation for the treatment of
Parkinson's disease: A systematic review.
AB - Objective Deep brain stimulation (DBS) for treatment of advanced Parkinson's
disease (PD) has two anatomical targets: the subthalamic nucleus (STN) and the
globus pallidus internus (GPI). The clinical effectiveness of these two
stimulation targets was compared in the present study. Methods A systematic
review and meta-analysis was performed to evaluated the postoperative changes in
the United Parkinson's Disease Rating Scale (UPDRS) on- and off-phase, on
stimulation motor scores; activities of daily living score (ADLS); and levodopa
equivalent dose (LED) after STN and GPI stimulation. Randomized and nonrandomized
controlled trials of PD treated by STN and GPI stimulation were considered for
inclusion. Results Eight published reports of eligible studies involving 599
patients met the inclusion criteria. No significant differences were observed
between the STN and GPI groups in the on-medication, on-stimulation UPDRS motor
score [mean difference, 2.15; 95% confidence interval (CI), -0.96-5.27] or ADLS
(mean difference, 3.40; 95% CI, 0.95-7.76). Significant differences in favor of
STN stimulation were noted in the off-medication, on-stimulation UPDRS motor
score (mean difference, 1.67; 95% CI, 0.98-2.37) and LED (mean difference,
130.24; 95% CI, 28.82-231.65). Conclusion The STN may be the preferred target for
DBS in consideration of medication reduction, economic efficiency, and motor
function improvement in the off phase. However, treatment decisions should be
made according to the individual patient's symptoms and expectations.
PMID- 28701062
TI - Prediction of the requirement of open reduction for developmental dysplasia of
the hip.
AB - Objective Closed reduction (CR) is a noninvasive treatment for developmental
dysplasia of the hip (DDH), and this treatment is confirmed intraoperatively.
This study aimed to develop a preoperative estimation model of the probability of
requiring open reduction (OR) for DDH. Methods The study design was cross
sectional by screening all patients younger than 2 years who had attempted CR
between October 2012 and July 2016 by a single surgeon. Potential diagnostic
determinants were sex, age, side, bilaterality, International Hip Dysplasia
Institute (IHDI) grade, and acetabular index (AI). An intraoperative arthrogram
was the reference standard. A logistic regression equation was built from a
reduced model. Bootstrapping was performed for internal validity. Results A total
of 164 hips in 104 patients who met the inclusion criteria were analysed. The
prevalence of CR was 72.2%. Independent factors for OR were older age, higher
IHDI grade, and lower AI. The probability of OR = 1/[1 + exp - (-2.753 + 0.112 *
age (months) + 1.965 * IHDI grade III (0 or 1) + 3.515 * IHDI grade IV (0 or 1) -
0.058 * AI (degrees)]. The area under the curve was 0.79. Conclusion This
equation is an objective tool that can be used to estimate the requirement for
OR.
PMID- 28701063
TI - Correction to: Islam et al., Evaluation of immunomodulatory effects of
zearalenone in mice.
PMID- 28701064
TI - Rosmarinic acid prevents fibrillization and diminishes vibrational modes
associated to beta sheet in tau protein linked to Alzheimer's disease.
AB - Alzheimer's disease is a common tauopathy where fibril formation and aggregates
are the hallmark of the disease. Efforts targeting amyloid-beta plaques have
succeeded to remove plaques but failed in clinical trials to improve cognition;
thus, the current therapeutic strategy is at preventing tau aggregation. Here, we
demonstrated that four phenolic diterpenoids and rosmarinic acid inhibit
fibrillization. Since, rosmarinic acid was the most active compound, we observe
morphological changes in atomic force microscopy images after treatment. Hence,
rosmarinic acid leads to a decrease in amide regions I and III, indicating that
rosmarinic acid prevents beta-sheet assembly. Molecular docking study inside the
steric zipper model of the hexapeptide 306VQIVYK311 involved in fibrillization
and beta sheet formation, suggests that rosmarinic acid binds to the steric
zipper with similar chemical interactions with respect to those observed for
orange G, a known pharmacofore for amyloid.
PMID- 28701065
TI - Predictors of biologic discontinuation due to insufficient response in patients
with rheumatoid arthritis who achieved clinical remission with biologic
treatment: A multicenter observational cohort study.
AB - OBJECTIVE: This study aimed to investigate predictors of biologic discontinuation
due to insufficient response as a surrogate for relapse in patients with
rheumatoid arthritis (RA) who achieved clinical remission with biologic
treatment. METHODS: This study was performed based on data from a multicenter
registry, and included 404 patients who achieved clinical remission within the
first year of treatment with their first biologic. Cumulative retention rate of
the first biologic was estimated using Kaplan-Meier curves, and the impact of
patient characteristics on biologic discontinuation was assessed with Cox
proportional hazards models. RESULTS: During follow-up, 50 patients discontinued
their first biologic due to insufficient response. Overall discontinuation rates
due to insufficient response after achieving remission were 6%, 11%, and 19% at
1, 2, and 5 years, respectively. Multivariate analysis revealed that concomitant
glucocorticoids at achieving remission [hazard ratio (HR): 3.80, 95% confidence
interval (CI): 1.89-7.64)] and a higher level of C-reactive protein (CRP) at
achieving remission (HR: 1.47 per 1 mg/dL, 95% CI: 1.09-1.99) independently
predict discontinuation due to insufficient response after achieving remission.
CONCLUSION: Patients with RA who achieved remission with concomitant
glucocorticoid treatment and a higher level of CRP are at high risk of subsequent
biologic discontinuation due to insufficient response.
PMID- 28701066
TI - The Cell Wall of the Human Fungal Pathogen Aspergillus fumigatus: Biosynthesis,
Organization, Immune Response, and Virulence.
AB - More than 90% of the cell wall of the filamentous fungus Aspergillus fumigatus
comprises polysaccharides. Biosynthesis of the cell wall polysaccharides is under
the control of three types of enzymes: transmembrane synthases, which are
anchored to the plasma membrane and use nucleotide sugars as substrates, and cell
wall-associated transglycosidases and glycosyl hydrolases, which are responsible
for remodeling the de novo synthesized polysaccharides and establishing the three
dimensional structure of the cell wall. For years, the cell wall was considered
an inert exoskeleton of the fungal cell. The cell wall is now recognized as a
living organelle, since the composition and cellular localization of the
different constitutive cell wall components (especially of the outer layers) vary
when the fungus senses changes in the external environment. The cell wall plays a
major role during infection. The recognition of the fungal cell wall by the host
is essential in the initiation of the immune response. The interactions between
the different pattern-recognition receptors (PRRs) and cell wall pathogen
associated molecular patterns (PAMPs) orientate the host response toward either
fungal death or growth, which would then lead to disease development.
Understanding the molecular determinants of the interplay between the cell wall
and host immunity is fundamental to combatting Aspergillus diseases.
PMID- 28701067
TI - Metabolomic approach to understand the acute and chronic hepatotoxicity of
Veratrum nigrum extract in mice based on ultra-high-performance liquid
chromatography coupled with quadrupole time-of-flight mass spectrometry.
AB - Veratrum nigrum L. (VN) is a poisonous traditional Chinese medicine herb present
since thousands of years in China. Clinical studies have shown that VN has the
ability to cause hepatotoxicity, which severely limits its clinical use. The
mechanism of its hepatotoxicity has not been fully elucidated. The purpose of
this study was to develop and characterize a model of acute and chronic
hepatotoxicity induced by Veratrum nigrum L. extract (VNE) to understand the
mechanism of liver tissue metabolomics approach using on ultra-high-performance
liquid chromatography coupled with quadrupole time-of-flight mass spectrometry
(UHPLC-Q-TOFMS). Mice were administered with VNE in the acute and chronic phases.
Histopathologic inspections and biochemistry analysis disclosed severe liver
damage after exposure to VNE. A partial least-squares discriminant analysis (PLS
DA) of the metabolomic profiles of rat liver tissues highlighted a number of
metabolic disturbances induced by VNE, focusing on purine and pyrimidine
metabolism, tryptophan metabolism, phospholipid metabolism, sphingolipid
metabolism and fatty acid metabolism. These findings could well explain VNE
induced acute and chronic hepatotoxicity and reveal several potential biomarkers
associated with this toxicity. This indicates that UHPLC-Q-TOFMS-based
metabolomics approach demonstrated its feasibility and allowed a better
understanding of VNE-induced liver toxicity dynamically.
PMID- 28701068
TI - Primary trapeziometacarpal prosthesis for complicated fracture of the base of the
thumb metacarpal.
PMID- 28701069
TI - Current Success and Efficiency of Autologous Ovarian Transplantation: A Meta
Analysis.
AB - CONTEXT: Ovarian cryopreservation followed by autotransplantation is still
considered an experimental strategy for fertility preservation (FP) mainly
because the success rates are unknown. OBJECTIVE: To determine cohort
epidemiologic characteristics and success rates of autologous ovarian tissue
transplantation (OTT) with previously cryopreserved tissue. MATERIALS AND
METHODS: Literature review from 1999 to October 1, 2016. Additional cases were
retrieved from meeting abstracts and own database. We selected studies that
reported autologous OTT with previously banked tissue in humans. We did not
include any cases involving fresh ovarian tissue transplantation or those
performed to treat idiopathic premature ovarian failure/insufficiency. Both
authors reviewed and selected studies for eligibility, which resulted in 59 full
text studies assessed for eligibility. Cases were extracted from original reports
and reviews by the junior author, and the senior author reviewed and verified the
extracted data. RESULTS: Nineteen reports were included for qualitative
synthesis. In 10 studies, detailed data were available to determine clinical and
live birth + ongoing (LB + OG) pregnancy as well as endocrine restoration rates.
Three hundred nine OTTs were performed with cryopreserved tissue, resulting in
the birth of 84 children and 8 OG pregnancies. The cumulative clinical and LB +
OG rates were 57.5% and 37.7%, respectively, and the endocrine restoration rate
was 63.9%. CONCLUSION: Success rates with cryopreserved OTT have reached
promising levels. Given these recent data, ovarian tissue cryopreservation should
be considered as a viable option for FP.
PMID- 28701070
TI - Development of a cognitive function test using virtual reality technology:
examination in healthy participants.
AB - We developed a virtual reality test to assess the cognitive function of Japanese
people in near-daily-life environment, namely, a virtual shopping test (VST). In
this test, participants were asked to execute shopping tasks using touch panel
operations in a "virtual shopping mall." We examined differences in VST
performances among healthy participants of different ages and correlations
between VST and screening tests, such as the Mini-Mental State Examination (MMSE)
and Everyday Memory Checklist (EMC). We included 285 healthy participants between
20 and 86 years of age in seven age groups. Therefore, each VST index tended to
decrease with advancing age; differences among age groups were significant. Most
VST indices had a significantly negative correlation with MMSE and significantly
positive correlation with EMC. VST may be useful for assessing general cognitive
decline; effects of age must be considered for proper interpretation of the VST
scores.
PMID- 28701071
TI - Sorption of organic pollutants frequently detected in stormwater: evaluation of
five potential sorbents.
AB - Adsorption filtration is one of the most promising techniques for removal of
dissolved, colloidal and particulate pollutants from stormwater. The aim of this
study was to compare the capacity of five filter materials - cellulose, chitosan,
chitosan-covered bark, pine bark and polypropylene/polyethylene (PP/PE) fibres -
to sorb organic pollutants frequently detected in stormwater, including
polycyclic aromatic hydrocarbons (PAHs), alkylphenols and phthalates. In batch
tests, synthetic stormwater spiked with a mixture of the organic compounds was
contacted with the materials for up to 24 h. The compounds were then liquid
liquid extracted and analysed using GC-MS. Cellulose and chitosan showed very low
sorption capacity for the organic contaminants, whereas >70% of the initial
concentration of most tested compounds was removed using PP/PE fibres, and >80%
with pine bark and chitosan-covered bark. The highest adsorption capacity was
found for PAHs (up to 44 ug/g) using PP/PE fibres and bark. For all tested
compounds, maximum sorption was approached within 30 min using these materials.
PMID- 28701072
TI - A novel biomimetic composite substitute of PLLA/gelatin nanofiber membrane for
dura repairing.
AB - OBJECTIVE: Biomimetic design will significantly improve growth and regeneration
of dural cells and tissue for better repairing effects and fewer complications in
repairing the native dura. This study designed a novel composite, biomimetic
substitute based on the characteristics of native dura extracellular matrix.
METHODS AND RESULTS: This substitute is expected to rapidly induce cell adhesion,
migration, and fast regeneration of neotissue. The material characteristics
(contact angle, surface charge, and zeta potential were evaluated), in vitro
biological characteristics (cell stretch, connections between cells, cell
proliferation) and in vivo tissue regeneration capability of this substitute were
evaluated, compared to those of collagen dura substitute, the mostly used dura
substitute. The results showed that the surface properties of this composite
substitute were more biomimetic to native extracellular matrix than collagen
substitute did, together with better cytocompatibility, tissue ingrowth, and
neoangiogenesis. This composite substitute further demonstrated in clinical case
study its ideal repair effect with no CSF leakage or other adverse reactions.
CONCLUSION: In conclusion, the new biomimetic composite substitute provides
alternative substitute for dura repairing.
PMID- 28701073
TI - The role of rhFGF-2 soaked polymer membrane for enhancement of guided bone
regeneration.
AB - The purposes of this study are to confirm the role of Fibroblast Growth Factor-2
(FGF-2) in bone regeneration by adding various concentrations of FGF-2 to the
collagen membrane and applying it to the Biphasic Calcium Phosphate (BCP) bone
graft site for guided bone regeneration, to explore the potential of collagen
membrane as FGF-2 carrier, and to determine the optimum FGF concentration for
enhancement of bone regeneration. Four bone defects of 8 mm in diameter were
created in 18 New Zealand rabbit calvaria. After BCP bone graft, graft material
was covered with collagen membranes adding various concentration of FGF-2. The
concentration of FGF-2 was set at 1.0, 0.5, 0.1 mg/ml, and same amount of saline
was used in the control group. To confirm the bone regeneration over time, six
New Zealand rabbits were sacrificed each at 2, 4, and 12 weeks, and the amounts
of new bone and residual bone graft material were analyzed by histologic and
histomorphometric analysis. Qualitative analyses are also conducted through
immunohistochemistry, Tetrate-resistant acid phosphatase (TRAP) stain and Russell
Movat pentachrome stain. As the healing period increased, the formation of new
bone increased and the amount of residual graft material decreased in all
experimental groups. Immunohistochemistry, TRAP staining and pentachrome staining
further showed that the addition of FGF-2 promoted bone regeneration in all
experimental groups. It was also confirmed that polymer collagen membrane can be
used as a useful carrier of FGF-2 when enhanced early stage of new bone formation
is required.
PMID- 28701074
TI - Pyrrolizidine alkaloids in floral honeys of tropical Ghana: a health risk
assessment.
AB - There is a vast amount of information about the nutritional and medicinal
properties of honey as a result of its numerous benefits. However, honeys have
been found to be contaminated with hepatotoxic and carcinogenic pyrrolizidine
alkaloids (PAs) on account of bees foraging on PA-containing plants. This study
deals with the analysis of PAs in tropical honeys emanating from different agro
ecological zones of Ghana in order to assess its potential health risk. PAs of 48
honey samples were analysed using high-performance liquid chromatography
electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS). The results
show that a total of 85% of the honeys from various agro-ecological zones were PA
positive including all honeys from supermarkets. The highest concentration of PAs
was 2639 MUg kg-1, while the average PA concentration of the samples was 283 MUg
kg-1. The study also found Chromolaena odorata pollens in majority of the honeys,
thus indicating the plant as major source of PA contamination of honeys in the
tropical regions.
PMID- 28701075
TI - The effect of orexin-A on motor and cognitive functions in a rat model of
Parkinson's disease.
AB - OBJECTIVE: The aim of this study was to evaluate the effect of orexin-A (OX-A)
and the orexin-1 receptor antagonist SB-334867 (SB) on motor and cognitive
functions in a rat model of Parkinson's disease. METHODS: Parkinson was induced
by intracerebroventricular (i.c.v) injection of 6- hydroxydopamine (6-OHDA) (200
MUg/rat). 72 h later, the treatment was initiated by i.c.v administration of SB
(30 nmol/rat) and/or OX-A (0.3 nmol/rat) for 10 days. Motor functions were
monitored using rotarod and hanging tests. Cognitive function was assessed by
passive avoidance test (Shuttle box). Results: OX-A administration in 6-OHDA
treated rats remarkably increased the time which animals run on rod (in rotarod
test) and also the latency to fall (in hanging test) (P < 0.01 and P < 0.001,
respectively). Conversely, administration of SB in 6-OHDA-treated rats decreased
the mentioned indices (P < 0.05 for latency to fall). Administration of agonist
and/or antagonist of orexin-1 receptors had no significant effect on 6-OHDA
induced cognitive impairment in rats. CONCLUSION: Results of this study suggest
that the orexinergic system might be involved in sensory-motor deficits of
Parkinson's disease.
PMID- 28701076
TI - Predictive value of stroke discharge diagnoses in the Danish National Patient
Register.
AB - AIMS: To determine the positive predictive values for stroke discharge diagnoses,
including subarachnoidal haemorrhage, intracerebral haemorrhage and cerebral
infarction in the Danish National Patient Register. METHODS: Participants in the
Danish cohort study Diet, Cancer and Health with a stroke discharge diagnosis in
the National Patient Register between 1993 and 2009 were identified and their
medical records were retrieved for validation of the diagnoses. RESULTS: A total
of 3326 records of possible cases of stroke were reviewed. The overall positive
predictive value for stroke was 69.3% (95% confidence interval (CI) 67.8-70.9%).
The predictive values differed according to hospital characteristics, with the
highest predictive value of 87.8% (95% CI 85.5-90.1%) found in departments of
neurology and the lowest predictive value of 43.0% (95% CI 37.6-48.5%) found in
outpatient clinics. CONCLUSIONS: The overall stroke diagnosis in the Danish
National Patient Register had a limited predictive value. We therefore recommend
the critical use of non-validated register data for research on stroke. The
possibility of optimising the predictive values based on more advanced algorithms
should be considered.
PMID- 28701077
TI - Older adults encode more, not less: evidence for age-related attentional
broadening.
AB - Previous work has shown that older adults attend to and implicitly remember more
distracting information than young adults; however, it is unknown whether they
show a corresponding decrease in implicit memory for targets in the presence of
distracters. Using implicit memory tests, we asked whether older adults show a
tradeoff in memory between targets and distracters. Here, young and older adults
performed a selective attention task in which they were instructed to attend to
target pictures and ignore superimposed distracter words. We measured priming for
distracter words using fragment completion and for target pictures using naming
time. Older adults showed greater priming for distracting words compared to young
adults, but equivalent priming for target pictures. These results suggest that
older adults have a broader attentional scope than young adults, encompassing
both relevant and irrelevant information.
PMID- 28701078
TI - Effects of context-aware patient guidance on blood pressure self-measurement
adherence levels.
AB - Hypertensive disease and preeclampsia are serious medical disorders affecting
pregnancy. Screening in early pregnancy may identify women at risk of developing
hypertensive disease and enable prophylactic treatment. Accurate blood pressure
measurement is an important part of this screening. The aim of this study was to
investigate whether patients, with the aid of a context-aware sensor-based blood
pressure self-measurement system, were able to correctly self-measure their blood
pressure adhering to internationally established recommendations. Furthermore, to
evaluate patient acceptance levels of performing self-measurements using context
aware adherence aids for guidance. A total of 100 pregnant women attending a
routine ultrasound, at gestational week 12, at the outpatient clinic of the
Department of Obstetrics and Gynecology, Aarhus University Hospital, were
recruited in the waiting room before the scheduled scan. Blood pressure self
measurement was performed using a blood pressure self-measurement system called
ValidAid consisting of a clinically approved blood pressure device, a sensor
chair registering rest-time, back-supported, legs-crossed, and ambient noise
levels respectively recording participant compliance, as well as a touch screen
based computer application with an interactive user interface for patient
guidance and feedback, as well as a built-in decision support system. Acceptance
of the automated self-measurement was evaluated by a questionnaire. In all, 99
percent followed the instructions with regard to both rest time and not talking.
For both of these, ValidAid offered interactive and context-aware guidance. The
recommendation of keeping legs uncrossed was only adhered to in 69 percent of
measurements and back supported in 35 percent of measurements. For both of these,
no interactive guidance was provided. The majority of the participants, 93
percent, felt comfortable using self-measurement equipment, while a minority of 8
percent would have preferred personnel-assisted measurements. The majority of
participants were able to take reliable blood pressure self-measurements. Results
indicate that recommendations that were not actively enforced were not followed
to the same extent as those that were enforced. Thus, providing interactive
context-aware guidance for all recommendations should be considered in the
future. Furthermore, we found patient acceptance levels of performing self
measurements to be overall positive.
PMID- 28701079
TI - MiR-185 inhibits 3T3-L1 cell differentiation by targeting SREBP-1.
AB - Adipogenesis involves a highly orchestrated series of complex events in which
microRNAs (miRNAs) may play an essential role. In this study, we found that the
miR-185 expression increased gradually during 3T3-L1 cells differentiation. To
explore the role of miR-185 in adipogenesis, miRNA agomirs and antagomirs were
used to perform miR-185 overexpression and knockdown, respectively.
Overexpression of miR-185 dramatically reduced the mRNA expression of the
adipogenic markers, PPARgamma, FABP4, FAS, and LPL, and the protein level of
PPARgamma and FAS. MiR-185 overexpression also led to a notable reduction in
lipid accumulation. In contrast, miR-185 inhibition promoted differentiation of
3T3-L1 cells. By target gene prediction and luciferase reporter assay, we
demonstrated that sterol regulatory element binding protein 1 (SREBP-1) may be
the target of miR-185. These results indicate that miR-185 negatively regulates
the differentiation of 3T3-L1 cells by targeting SREBP-1, further highlighting
the importance of miRNAs in adipogenesis.
PMID- 28701080
TI - [Formula: see text]Neurocognitive outcomes in children with unilateral basal
ganglia arterial ischemic stroke and secondary hemidystonia.
AB - Dystonia is a movement disorder that involves excessive, involuntary muscle
contractions resulting in repetitive movements and/or abnormal posturing. One
common cause of unilateral dystonia in childhood is ischemic stroke involving the
basal ganglia and/or thalamus. Virtually nothing is known about
neuropsychological outcomes in children who have dystonia following basal ganglia
stroke. The present study explored whether or not children with secondary
dystonia experience additional cognitive challenges when compared to children
with similar patterns of brain injury, but no dystonia. We examined intellectual
function, academics, and several aspects of executive function in children with
unilateral basal ganglia stroke during childhood, comparing those with dystonia
and those without. Although groups did not differ in terms of lesion size, we
found significantly lower performance on measures of verbal and nonverbal
reasoning, inhibitory control, and academic ability in children with secondary
dystonia compared to those without. In contrast, there were no significant group
differences on parent ratings of their child's executive function in daily life.
These findings suggest that maladaptive reorganization following basal ganglia
stroke may contribute to the development of secondary dystonia and also to poor
intellectual and academic outcomes in this group.
PMID- 28701081
TI - Gut microbiota dysbiosis associated with glucose metabolism disorders and the
metabolic syndrome in older adults.
AB - Obesity and associated metabolic disorders have become highly prevalent diseases
worldwide, and the human gut microbiota, due to its influence on host energy
metabolism, has been attributed an important role therein. This pilot study
explores host-microbiota relationships in men and women affected by various types
of glucose metabolism disorder. Among 20 individuals aged 58 to 71 years with
either normal glucose tolerance, prediabetes, or type 2 diabetes mellitus the gut
bacterial communities were compared based on barcoded 454 sequencing of 16S rRNA
genes amplified from stool samples. We found that specific microbiota groups were
relatively enriched or reduced in different metabolic states. Further, positive
or negative associations with clinical manifestations of metabolic disease
suggest that these organisms indicate and possibly contribute to metabolic
impairment or health. For instance, a higher prevalence of Erysipelotrichaceae
and Lachnospiraceae was found associated with metabolic disorders, and the
Holdemania and Blautia genera correlated with clinical indicators of an impaired
lipid and glucose metabolism. The Bacteroidetes and groups therein, by contrast,
displayed inverse relationships with metabolic disease parameters and were found
relatively enriched in participants not diagnosed with metabolic syndrome or
obesity. Further, the prevalence of specific Clostridia and Rikenellaceae members
also pointed towards a healthier metabolic state. Links with diet as an
intermediate factor included positive and negative associations of
Lachnospiraceae with relative consumption rates of fat and carbohydrates,
respectively, and positive associations of Turicibacteraceae with the consumption
of protein. Identifying critical roles of major gut microbiota components in
metabolic disorders has important translational implications regarding the
prevention and treatment of metabolic diseases by means of preventing or
reversing dysbiosis and by controlling exacerbating diet and life style factors
particularly in sensitive population groups.
PMID- 28701082
TI - Bovine mastitis prevention: humoral and cellular response of dairy cows
inoculated with lactic acid bacteria at the dry-off period.
AB - The use of lactic acid bacteria (LAB) in animal feed, constitute an alternative
tool for bovine mastitis prevention. Previously, two LAB strains were isolated
from bovine milk and selected for their probiotics properties. So far, immune
response of inoculating LAB in bovine udders at dry-off period has not been
investigated. The immunoglobulin isotype levels and memory cell proliferation in
blood and milk of animals inoculated with Lactobacillus lactis subsp. lactis
CRL1655 and Lactobacillus perolens CRL1724 at dry-off period was studied. Ten
animals were inoculated intramammarily with 106 cells of each LAB (IG) and 2
animals used as control (NIG). Milk and blood samples were taken before
inoculation and 1, 2, 4, 6, 12 and 24 h and 7 and 14 days after inoculation.
Somatic cell count (SCC) in milk, the presence of bovine mastitis pathogens, the
levels of antibodies and lymphocyte proliferation were determined. In the IG, the
SCC was <250,000 cells/ml up to 4 h after intramammary inoculation. Six and 12 h
after inoculation, the SCC increased up to 600,000 and 2,000,000 cells/ml,
respectively. In the NIG, the SCC reached the maximum value 7 days after
inoculation. Microbiological analysis showed that all samples were negative for
major bovine mastitis pathogens after 24-48 h of incubation. In general, LAB
inoculation increased the amount of IgG isotypes in blood and milk, and these
antibodies were able to recognise Staphylococcus aureus epitopes. Lymphocytes
proliferation was significantly higher in the IG at all time points assayed,
following LAB or S. aureus stimulation. The lymphocytes of animals inoculated
with LAB do not react in vitro to the presence of S. aureus antigen.. The results
showed that probiotic microorganisms could be a natural and effective alternative
in the prevention of bovine mastitis at dry-off period and act as
immunomodulatory stimulating local and systemic defence lines.
PMID- 28701083
TI - Collaborative development of an educational resource on rehabilitation for people
living with HIV.
AB - OBJECTIVE: The objective of this study is to describe the collaborative
development of a rehabilitation guide for people living with human
immunodeficiency virus (HIV) which was adapted from an online resource for
clinicians. METHODS: We adapted a comprehensive evidence-informed online clinical
resource for people living with HIV using a three-phase participatory process. In
Phase 1, we interviewed 26 clinicians and 16 people living with HIV to gather
recommendations on how to adapt and format the content to benefit people living
with HIV. In Phase 2, we adapted the patient education resource using the
recommendations that emerged from Phase 1. Phase 3 consisted of comprehensive
stakeholder review of the revised resource on the adaptability, usability,
communicability, and relevance of the information. Stakeholders participated in
an interview to obtain in-depth information on their perspectives. Transcribed
interviews underwent qualitative content analysis. RESULTS: Stakeholders
indicated that the e-guide had utility for people living with HIV, community HIV
service organizations, and care providers. CONCLUSION: Engaging people living
with HIV resulted in a more relevant and meaningful resource that incorporated
patients' values, needs, and preferences. IMPLICATIONS: Involving multiple
stakeholders and user groups in the adaptation and evaluation of online patient
education resources can assist in meeting patients' needs through increasing the
relevance, organization and presentation of the content, and incorporating
patients' values and needs. Implications for Rehabilitation Online patient
education resources should be adapted in order to maximize relevance and
meaningfulness to patients. Involving multiple stakeholders in the adaptation and
evaluation of online patient education resources can assist in meeting patients'
needs. Involving multiple stakeholders increases the relevance, organization and
presentation of the content and allows the incorporation of patient values and
needs. This collaborative approach with an emphasis on meaningful participation
of patients and community may be of interest to others interested in promoting
knowledge translation.
PMID- 28701084
TI - Telepsychiatry and social psychiatry.
PMID- 28701086
TI - Rights of people with mental disorders: Realities in healthcare facilities in
Tunisia.
AB - BACKGROUND: Mental disorders have been associated worldwide with human rights'
violations. Controversially, many occur in mental health facilities. AIM: This
work aimed to assess the rights of people with mental disorders in healthcare
facilities in Tunisia. METHODS: A cross-sectional study, using the World Health
Organization (WHO) quality-rights toolkit, assessed the human rights levels of
achievement in Elrazi Hospital, the only psychiatric hospital in Tunisia, in
comparison with the National Institute of Nutrition (NIN). The framework was the
Convention on the Rights of Persons with Disabilities (CRPD). The assessment was
carried through observation, documentation review, and interviews with service
users, staff, and family members. The sample was composed of 113 interviewees.
RESULTS: In Elrazi Hospital, three out of the five evaluated rights were assessed
as only initiated: the right to an adequate standard of living, to exercise legal
capacity and to be free from inhuman treatment. By comparison, these rights were
partially achieved in the NIN. The right to enjoyment of the highest attainable
standard of health was partially achieved and the right to live independently and
to be included in the community was not even initiated. These last two rights
were at the same level of achievement in the NIN. CONCLUSION: Significant
improvements are needed to adapt the practice in Elrazi Hospital to comply with
human rights, especially since the achievement level of these rights is lower
than in a non-psychiatric hospital. Our study emphasizes the importance of
spreading the CRPD as a standardized framework.
PMID- 28701087
TI - Epidemiological characteristics associated with uptake of pneumococcal vaccine
among older adults living in the community in Singapore: Results from the
National Health Surveillance Survey 2013.
AB - AIMS: In Singapore, pneumococcal vaccination is recommended for the elderly (i.e.
those >=65 years of age) and people with chronic medical conditions. We
investigated epidemiological characteristics associated with the uptake of
pneumococcal vaccine based on a nationally representative cross-sectional sample
of community-living adults aged >=50 years. METHODS: The data were obtained from
the National Health Surveillance Survey (NHSS) 2013. Associations between
pneumococcal vaccination and sociodemographic and health-related variables were
analysed using univariable and multivariable logistic regression models. RESULTS:
Among 3672 respondents aged >=50 years in the NHSS, 7.8% had taken the
pneumococcal vaccination. A higher level of education and higher monthly
household income were sociodemographic characteristics independently associated
with pneumococcal vaccine uptake. Health-related characteristics predictive of
pneumococcal vaccine uptake were better self-rated health and having a regular
family doctor/general practitioner. Among those who responded to the two
questions on vaccinations, 3.9% had been vaccinated against both seasonal
influenza and pneumococcal infection, while 11.1% had taken only seasonal
influenza vaccination in the past year. CONCLUSIONS: There is a need to boost
pneumococcal vaccination coverage among community-dwelling older adults. These
findings provide insights into reviewing and tailoring public-health strategies
and programmes to increase vaccine uptake in at-risk population groups.
PMID- 28701088
TI - Early-onset schizophrenia: Symptoms and social class of origin.
AB - BACKGROUND: The genesis of schizophrenia is multifactorial, including biological
and environmental risk factors. We tested for an interactive effect between early
onset schizophrenia (EOS) and social class of origins (socioeconomic status
(SES)). Data were further analyzed for a possible connection to type of
schizophrenic symptoms. Sampling/Methods: Data for the study are taken from the
medical records of 642 patients from a large state hospital in the northeastern
United States. Clinical assessments were divided into positive and negative
symptomatology through application of the Scale for the Assessment of Negative
Symptoms (SANS), the Scale for the Assessment of Positive Symptoms (SAPS) and the
Positive and Negative Syndrome Scale (PANSS). Detailed information about age of
onset and SES of origin was obtained through Social Service Assessment
interviews. RESULTS: We uncovered a significant impact of EOS among the poor that
elevates risk for negative symptomatology. CONCLUSION: Poor SES alone does not
increase the likelihood of EOS, but it magnifies the deleterious effect of EOS on
negative symptoms. Future research on these variables may inform the relative
contribution of each.
PMID- 28701089
TI - Increased risk of herpes zoster in patients with coeliac disease - nationwide
cohort study.
AB - BACKGROUND AND AIMS: Clinical experience suggests that patients with coeliac
disease (CD) are more prone to develop herpes zoster (HZ), but robust studies are
lacking. METHODS: We identified 29,064 patients with CD 1969-2008 using biopsy
report data from Sweden's 28 pathology departments. CD was equalled to villous
atrophy (Marsh histopathology grade III). Each patient was matched on age, sex,
calendar year and county of residence to up to five reference individuals (
n=144,342) from the general population. We then used Cox regression to estimate
hazard ratios (HRs) for future HZ (defined as having a hospital-based inpatient
or outpatient record of this diagnosis in the Swedish Patient Register). RESULTS:
During follow-up, 154 (0.53%) individuals with CD and 499 (0.35%) reference
individuals developed HZ. Among individuals aged >=60 years, 1.06% of CD
individuals and 0.85% of reference individuals had a lifetime record of HZ.
Overall, CD was associated with a 1.62-fold increased risk of HZ (95% CI=1.35
1.95), and was seen also when we considered comorbidity with lymphoproliferative
disease, systemic lupus erythematosus, type 1 diabetes, thyroid disease,
rheumatoid disease and excluded individuals with a record of dermatitis
herpetiformis. The increased risk remained significant after more than five years
of follow-up (1.46; 1.16-1.84) Conclusions: CD is associated with HZ, the
increased relative risk persists over time from celiac diagnosis but the absolute
risk is small.
PMID- 28701090
TI - [Transference Focused Psychotherapy for Borderline-Adolescents in a Day Clinic
Treatment Program].
AB - Transference Focused Psychotherapy for Borderline-Adolescents in a Day Clinic
Treatment Program This paper focuses on the concept of transference focused
psychotherapy (TFP) modified for juvenile borderline patients. Adolescents with
borderline developmental personality disorder (bpd) have an essential deficit in
their personality structure that leads to oscillations in their self-esteem and
in a "split" perception of the world. They suffer from a variety of symptoms and
severe impairments on their own and their families' quality of life. Their
fragmented perception of themselves and others make relationships almost
unbearable for them. Relationships are mostly marked by severe anxiety of
resentment and rejection. For these patients this causes intolerable trouble at
school where every day conflicts take place. Self-mutilation and suicidal
thoughts often seem the only way out. By now, there is an agreement that an early
specialized assessment and treatment is necessary in order to stop the typical
consequences of their self-mutilative and dysfunctional behavior. Still, in
contrast to adult age, empirical evidence is missing which proves the
effectiveness of treating adolescent borderline patients. In this paper we
present a research project on the effectiveness of transference focused
psychotherapy with adolescent borderline patients (TFP-A) in a day clinic
setting, combining TFP with group skills training as known from dialectic
behavior therapy (DBT). Furthermore, we give first results on analyzing the
effectiveness of our day clinic treatment program based on TFP-A, focusing on
improving core symptoms such as affective problems, aggressive behavior against
self and others and interpersonal problems.
PMID- 28701091
TI - [Mentalization-Based Treatment for Adolescents with Borderline Personality
Disorder - Concept and Efficacy].
AB - Mentalization-Based Treatment for Adolescents with Borderline Personality
Disorder - Concept and Efficacy In recent years, the concept of mentalization has
become increasingly important in practice and research. It describes the
imaginative ability to understand human behavior in terms of mental states.
Mentalization is a central component to understand the etiology and to treat
patients with borderline personality disorder (BPD). Both adult and adolescent
patients with BPD have limited mentalization abilities, which can be reliably
assessed using the Reflective Functioning Scale. Mentalization-Based Treatment
(MBT) was originally developed as an integrative approach for the treatment of
adult patients with BPD. It is a manualized psychotherapy with psychodynamic
roots with the aim to increase mentalizing abilities of patients. Since then, MBT
has been further developed for other mental disorders as well as for the
treatment of different age groups. One of these developments is MBT for
Adolescents (MBT-A). MBT-A includes both individual as well as family sessions
and the average duration of therapy is about twelve months. MBT-A can be applied
in inpatient and outpatient settings and aims to improve mentalizing abilities in
emotionally important relationships and the whole family system. First studies
have found evidence for the efficacy of MBT-A. A randomized controlled trial
(RCT) is currently being carried out to evaluate the efficacy of MBT-A for
adolescents with conduct disorder. However, further evidence for efficacy and
further conceptual development is needed.
PMID- 28701093
TI - [Editorial].
PMID- 28701096
TI - [The Outpatient Clinic for Adolescent Risk-taking and Self-harm behaviors
(AtR!Sk) - A Pioneering Approach of Outpatient Early Detection and Intervention
of Borderline Personality Disorder].
AB - The Outpatient Clinic for Adolescent Risk-taking and Self-harm behaviors (AtR!Sk)
- A Pioneering Approach of Outpatient Early Detection and Intervention of
Borderline Personality Disorder Self-harm and risk-taking behaviors are
frequently occurring problems in adolescents' everyday life and commonly
challenge the present child and adolescent health-care system. Those behaviors
are typical features of borderline-personality disorder (BPD), a severe mental
disorder that is associated with immense psychological strain, increased risk of
mortality and poor psychosocial functioning. Despite controversy in the past,
recent evidence shows that BPD is a valid and reliable diagnosis in adolescence.
Consequently, specified and effective intervention programs for this age group
are necessary. Instead, present health-care services for children and adolescents
in Germany are usually characterized by long waiting periods for specialized
outpatient treatments and unnecessary expanses of unnecessary long inpatient
stays. Alternatively, and in order to prevent serious long-term consequences, new
concepts - integrated in an ambulatory setting and close to patients' daily
routines - should focus on early detection and treatment of adolescents at-risk
presenting with borderline personality features. The specialist outpatient clinic
AtR!Sk at the University Hospital Heidelberg ensures a low-threshold initial
contact service, comprehensive and accurate diagnosis of BPD features, and
rapidly "tailored" therapy for young people presenting with any types of risk
taking and self-harm behavior. AtR!Sk - as a pioneering approach in south Germany
- provides evidence-based early detection and intervention for adolescent BPD.
PMID- 28701097
TI - [The Psychoanalytic-interactional Method (PIM): A Psychodynamic Treatment for
Adolescents with Severe Disorders of Personality Functioning].
AB - The Psychoanalytic-interactional Method (PIM): A Psychodynamic Treatment for
Adolescents with Severe Disorders of Personality Functioning The psychoanalytic
interactional method (PIM) was developed as a psychodynamic treatment for adult
patients with severe disorders of personality functioning (Streeck u.
Leichsenring, 2015). However, it is also well suited for the treatment of
adolescent patients because its techniques fit with specific conditions of
adolescence. A modified version of the PIM for adolescents (Streeck-Fischer,
Cropp, Streeck, Salzer, 2016) has proven to be efficacious. The paper describes
the basic principles of the PIM and names aspects that have to be taken into
account in the treatment of adolescents with severe disorders of personality
functioning. Finally, previous empirical results regarding the PIM treatment in
adolescence are presented.
PMID- 28701098
TI - [AIT (Adolescent Identity Treatment) - an Integrative Treatment Model for the
Treatment of Personality Disorders].
AB - AIT (Adolescent Identity Treatment) - an Integrative Treatment Model for the
Treatment of Personality Disorders Personality disorders are patterns of
maladaptive personality traits that have an impact on the individual throughout
the life span. Borderline Personality Disorder (BPD) is a very severe, but
treatable mental disorder. Identity disturbance is seen as the central construct
for detecting severe personality pathology - and, most notably, borderline
personality disorder - in adults and adolescents. Crises in the development of
identity usually resolve into a normal and consolidated identity with flexible
and adaptive functioning whereas identity diffusion is viewed as a lack of
integration of the concept of the self and significant others. It is seen as the
basis for subsequent personality pathology, including that of borderline
personality disorder. Although BPD has its onset in adolescence and emerging
adulthood the diagnosis is often delayed. In most cases, specific treatment is
only offered late in the course of the disorder and to relatively few
individuals. Adolescent Identity Treatment (AIT) is a treatment model that
focuses on identity pathology as the core characteristic of personality
disorders. This model integrates specific techniques for the treatment of
adolescent personality pathology on the background of object-relation theories
and modified elements of Transference-Focused Psychotherapy. Moreover,
psychoeducation, a behavior-oriented homeplan and intensive family work is part
of AIT.
PMID- 28701100
TI - Intervention analysis of the safety effects of a legislation targeting excessive
speeding in Canada.
AB - Excessive speeding is a major traffic safety concern consequently, numerous
countermeasures have been considered to mitigate this problem. Excessive
speeding, street racing and stunt driving activities subject all road users to
extreme risk. To address this problem, three Canadian provinces introduced severe
sanctions against drivers who exceed speed limits by high margins. Under the laws
offenders were subject to immediate license suspension and vehicle impoundment.
In this paper, intervention analysis of the collision data from the three
provinces was conducted to identify the safety effects of the legislation. The
analysis aims to identify changes in the time series behaviour of collision data
after the adoption of the law. The changes were assessed for statistical
significance, and the magnitude of the change was quantified. In general, the
paper showed that the legislative changes were associated with drops in province
wide fatal collisions substantiating the safety benefits of introducing such
legislation against excessive speeders.
PMID- 28701101
TI - Validation of an immersive virtual reality system for training near and far space
neglect in individuals with stroke: a pilot study.
AB - BACKGROUND: Unilateral spatial neglect (USN) is defined as impaired ability to
attend and see on one side, and when present, it interferes seriously with daily
life. These symptoms can exist for near and far spaces combined or independently,
and it is important to provide effective intervention for near and far space
neglect. OBJECTIVE: The purpose of this pilot study was to propose an immersive
virtual reality (VR) rehabilitation program using a head-mounted display that is
able to train both near and far space neglect, and to validate the immediate
effect of the VR program in both near and far space neglect. METHODS: Ten USN
patients underwent the VR program with a pre-post design and no control. In the
virtual environment, we developed visual searching and reaching tasks using an
immersive VR system. Behavioral inattention test (BIT) scores obtained pre- and
immediate post-VR program were compared. RESULTS: BIT scores obtained pre- and
post-VR program revealed that far space neglect but not near space neglect
improved promptly after the VR program. This effect for far space neglect was
observed in the cancelation task, but not in the line bisection task.
CONCLUSIONS: Positive effects of the immersive VR program for far space neglect
are suggested by the results of the present pilot study. However, further studies
with rigorous designs are needed to validate its clinical effectiveness.
PMID- 28701102
TI - Mechanism of action of mRNA-based vaccines.
AB - INTRODUCTION: The present review summarizes the growing body of work defining the
mechanisms of action of this exciting new vaccine technology that should allow
rational approaches in the design of next generation mRNA vaccines. Areas
covered: Bio-distribution of mRNA, localization of antigen production, role of
the innate immunity, priming of the adaptive immune response, route of
administration and effects of mRNA delivery systems. Expert commentary: In the
last few years, the development of RNA vaccines had a fast growth, the rising
number of proof will enable rational approaches to improving the effectiveness
and safety of this modern class of medicine.
PMID- 28701104
TI - A document analysis of drowning prevention education resources in the United
States.
AB - There have been long-standing calls to better educate the public at large on
risks of drowning; yet limited evaluation has taken place on current resources in
circulation. The purpose of this qualitative research is to develop an
understanding of the content in currently circulated drowning prevention
resources in the United States. Data points (n = 451) consisting of specific
content within 25 different drowning prevention educational resources were
analyzed using document analysis methods; a grounded theory approach was employed
to allow for categorical development and indexing of the data. Results revealed
six emerging categories, including safety precautions (n = 152), supervision (n =
109), preventing access (n = 57), safety equipment (n = 46), emergency procedures
(n = 46), and aquatic education (n = 41). Results provide an initial insight into
the composition of drowning prevention resources in the United States and provide
a foundation for future research.
PMID- 28701105
TI - The use of evidence during group meetings of Dutch general practitioners.
AB - BACKGROUND AND OBJECTIVES: For Evidence Based Medicine (EBM) learning journal
clubs are recommended, but these are not common practice. How participants
discuss and learn about applying evidence in other group meetings is unknown. We
examined different types of group meetings and explored the use of, and
discussions about, clinical research evidence. METHODS: A mixed-methods study
design was adopted. After distribution and analysis of a questionnaire about
types of group meetings, interviews were conducted to better understand the most
frequently occurring type. RESULTS: GPs have different types of meetings, but the
most common group meetings where evidence wass discussed were so called quality
circles, i.e. pharmacotherapy audit meetings in which GPs discuss drug
prescription figures or preferred treatment together with pharmacists. Interviews
showed that the source of evidence used mostly are the recommendations in the
national GP guidelines. The underlying evidence or new research did not play an
important role in the discussions. CONCLUSIONS: Quality circles seem to be more
goal-oriented than learning oriented. Learning discussions about controversies in
clinical research or about the integration of evidence, patient values and
clinical expertise occurred infrequently. To harvest the potential value of group
meetings for EBM learning, quality circles in their present design are not
optimal.
PMID- 28701103
TI - Lipid management among individuals with inflammatory arthritis in the national
REasons for Geographic And Racial Differences in Stroke (REGARDS) cohort.
AB - Objective Hyperlipidemia guidelines do not currently identify inflammatory
arthritis (IA) as a cardiovascular disease (CVD) risk factor. We compared
hyperlipidemia treatment of individuals with and without IA (rheumatoid
arthritis, psoriatic arthritis, or ankylosing spondylitis) in a large national
cohort. Methods Participants from the REasons for Geographic And Racial
Differences in Stroke (REGARDS) study were classified as having IA (without
diabetes or hypertension); diabetes (but no IA); hypertension (but no diabetes or
IA); or no IA, diabetes, or hypertension. Multivariable logistic regression
models examined the odds of medical treatment among those with hyperlipidemia.
Results Thirty-nine participants had IA, 5423 had diabetes, 7534 had
hypertension, and 5288 had no diabetes, hypertension, or IA. The fully adjusted
odds of treatment were similar between participants with IA and those without IA,
hypertension, or diabetes. Participants with diabetes and no IA and participants
with hypertension and no IA were twice as likely to be treated for hyperlipidemia
as those without IA, diabetes, or hypertension. Conclusion Despite their higher
CVD risk, patients with IA were as likely to be treated for hyperlipidemia as
those without diabetes, hypertension, or IA. Lipid guidelines should identify IA
as a CVD risk factor to improve CVD risk optimization in IA.
PMID- 28701106
TI - Insights into the diagnosis and management of iron deficiency in inflammatory
bowel disease.
AB - INTRODUCTION: Iron deficiency is a frequent comorbidity of chronic diseases such
as inflammatory bowel disease that can severely impact the health and quality of
life of affected individuals. It can exist as a silent condition and manifest in
non-specific symptoms even in the absence of anemia. Even though iron deficiency
anemia is the most common complication and extra-intestinal manifestation of
inflammatory bowel disease, the majority of inflammatory bowel disease patients
who are diagnosed with iron deficiency anemia are not treated. Areas covered: In
this review, we discuss iron deficiency and iron deficiency anemia in patients
with inflammatory bowel disease, and review diagnostic and therapeutic options.
Expert commentary: We invite international gastroenterological societies and
associations to refine the practice guidelines and include iron deficiency as a
potential morbidity associated with IBD in analogy to arthritis, uveitis or any
other extra intestinal manifestations. There should a more unanimous agreement
among different societies on the specific diagnostic cutoff values for C-reactive
protein levels, serum ferritin, and transferrin saturation in order to
differentiate iron deficiency anemia from anemia of chronic disease.
PMID- 28701107
TI - Overcoming resistance to EGFR tyrosine kinase inhibitors in lung cancer, focusing
on non-T790M mechanisms.
AB - INTRODUCTION: despite initial dramatic efficacy of EGFR tyrosine kinase
inhibitors (TKIs) in EGFR-mutant lung cancer patients, emergence of acquired
resistance is almost inevitable. The EGFR T790M secondary mutation that accounts
for ~50% of resistance is now treatable with osimertinib. However, for the
remaining 50% of patients who develop resistance mechanisms other than T790M
mutation, cytotoxic chemotherapies are still the standard of care and novel
treatment strategies are urgently needed. Areas covered: In this review, we
discuss current experimental and clinical evidence to develop better treatment
strategies to overcome or prevent acquired resistance to EGFR-TKIs in lung
cancers, focusing on non-T790M mechanisms. Expert commentary: There are numerous
non-T790M resistant mechanisms to EGFR-TKIs, and therefore, strategies that can
be applied to many of these resistance mechanisms may be reasonable and useful in
clinical practice. Although the combination of cytotoxic chemotherapy plus an
EGFR-TKI has proved to be detrimental following front-line EGFR-TKI treatment
failure, promising experimental and/or early clinical data have been reported for
the combination of bevacizumab or anti-EGFR monoclonal antibody plus EGFR-TKIs.
Upfront polytherapy, which co-targets potential resistance mechanisms or other
important signaling for EGFR-mutant lung cancer cells, is also a promising
strategy.
PMID- 28701108
TI - Repetitive Mild Closed Head Injury Alters Protein Expression and Dendritic
Complexity in a Mouse Model.
AB - Worldwide head injuries are a growing problem. In the United States alone, 1.7
million people suffer a head injury each year. While most of these injuries are
mild, head injury sufferers still sustain symptoms that can have major medical
and economical impacts. Moreover, repetitive mild head injuries, like those
observed in active military personnel and athletes, have demonstrated a more
severe and long-term set of consequences. In an effort to better understand the
delayed pathological changes following multiple mild head injuries, we used a
mouse model of mild closed head injury (with no motor deficits observed by
rotarod testing) and measured dendritic complexity at 30 days after injury and
potentially related factors up to 60 days post-injury. We found an increase in
TDP-43 protein at 60 days post-injury in the hippocampus and a decrease in
autophagy factors three days post-injury. Alterations in dendritic complexity
were neuronal subtype and location specific. Measurements of neurotropic factors
suggest that an increase in complexity in the cortex may be a consequence of
neuronal loss of the less connected neurons.
PMID- 28701109
TI - Emotion processing in persons who respond vicariously towards others in pain:
Disinhibited left-lateralized neural activity for threatening expressions.
AB - We investigated emotional processing in vicarious pain (VP) responders. VP
responders report an explicit sensory and emotional feeling of pain when they
witness another in pain, which is greater in magnitude than the empathic
processing of pain in the general population. In Study 1, 31 participants
completed a chimeric faces task, judging whether emotional chimera in the left,
or right, visual field was more intense. VP responders took longer to judge
emotionality than non-responders, and fixated more on the angry hemiface in the
right visual field, whereas non-responder controls had no lateralized fixation
bias. In Study 2, blood-oxygen level-dependent signals were recorded during an
emotional face matching task. VP intensity was correlated with increased insula
activity and reduced middle frontal gyrus activity for angry faces, and with
reduced activity in the inferior and middle frontal gyri for sad faces. Together,
these findings suggest that VP responders are more reactive to negative emotional
expressions. Specifically, emotional judgements involved altered left-hemisphere
activity in VP responders, and reduced engagement of regions involved in emotion
regulation.
PMID- 28701110
TI - The Traditional Model Does Not Explain Attitudes Toward Euthanasia: A Web-Based
Survey of the General Public in Finland.
AB - The debate about euthanasia is ongoing in several countries including Finland.
However, there is a lack of information on current attitudes toward euthanasia
among general Finnish public. The traditional model for predicting individuals'
attitudes to euthanasia is based on their age, gender, educational level, and
religiosity. However, a new evaluation of religiosity is needed due to the
limited operationalization of this factor in previous studies. This study
explores the connections between the factors of the traditional model and the
attitudes toward euthanasia among the general public in the Finnish context. The
Finnish public's attitudes toward euthanasia have become remarkably more positive
over the last decade. Further research is needed on the factors that predict
euthanasia attitudes. We suggest two different explanatory models for
consideration: one that emphasizes the value of individual autonomy and another
that approaches euthanasia from the perspective of fears of death or the process
of dying.
PMID- 28701111
TI - Mothers' Grief, Forgiveness, and Posttraumatic Growth After the Loss of a Child.
AB - The aim of this study was to investigate maternal grief after losing a child in
relation to forgiveness and posttraumatic growth. A sample of 60 grieving mothers
from Slovakia completed the following battery: The Texas Revised Inventory of
Grief, a modified version of the Enright Forgiveness Inventory, and the
Posttraumatic Growth Inventory. The results showed a negative association between
forgiveness and grief and a strong positive association between forgiveness and
posttraumatic growth, which was not moderated by the time elapsed since the loss.
Semistructured interviews were conducted with 12 mothers. The data were analyzed
through Consensual Qualitative Research to gain deeper understanding of
forgiveness and posttraumatic growth experiences after the loss of a child.
Categories and subcategories are discussed.
PMID- 28701112
TI - An Exploratory Study on University Students' Perceptions of Posthumous Organ
Donation Base on the Theory of Reasoned Action.
AB - In view of the general support for organ donation but low registration rate in
Hong Kong, the present research attempted to understand the attitude-behavior
inconsistency by identifying the underlying beliefs for organ donation through
employing the theory of reasoned action. A qualitative approach using semi
structured focus groups was adopted and 19 students from three universities in
Hong Kong participated; 10 constructs were identified: attitude, subjective norm,
helping, continuation, contribution, body intact, distrust to the medical system,
indifference to organ donation, negative affect, and family burden. Findings
suggested that their attitudes toward organ donation were of both the cognitive
and affective nature; subjective norm of family, friends, and people they respect
were identified as influential to students' views on organ donation. The study
provided insight in promoting organ donation, that the cognitive concerns about
keeping the body intact, and the negative affects introduced should also be
addressed.
PMID- 28701115
TI - Comparing Facilitator Priorities of Suicide Survivor Support Groups: A Cross
Cultural Comparison Between Japanese and American Groups.
AB - A total of 56 Japanese and 59 American survivor of suicide support group
facilitators were asked to rank the mutual aid objectives of their groups
following Shulman's scheme in terms of their frequency and importance. Both
American and Japanese facilitators showed an emphasis on personal adaptation
goals (such as helping bereaved feel less isolated in their grief or encouraging
bereaved to share their coping with loss experiences) over collective goals (such
as raising monies for more research on mental illness or trying to combat
societal suicide stigma in their local communities). Differences were also noted
with American facilitators evaluating helping with problem solving, sharing
different ways of coping, viewing personal issues as societal problems, and
advocating for promoting social change as significantly higher than the Japanese
did. We believe some of these contrasts reflect differences in American and
Japanese cultural values.
PMID- 28701116
TI - Effectiveness of a Grief Intervention for Caregivers of People With Dementia.
AB - In this article, we report on the structure and effectiveness of a grief
management coaching intervention with caregivers of individuals with dementia.
The intervention was informed by Marwit and Meuser's Caregiver Grief Model and
considered levels of grief, sense of empowerment, coping, and resilience using
five methods of delivery. Results indicate that the intervention had significant
positive effects on caregivers' levels of grief and increased their levels of
empowerment, coping, and resilience. The intervention was found to be effective
across caregivers' characteristics as well as across five delivery modalities.
Through description of this intervention, as well as outcome, this research
contributes to the body of knowledge about caregivers' disenfranchised grief and
ways to effectively address it.
PMID- 28701117
TI - Antibiotics for acute respiratory infections in general practice: comparison of
prescribing rates with guideline recommendations.
AB - OBJECTIVE: To compare the current rate of antibiotic prescribing for acute
respiratory infections (ARIs) in Australian general practice with the
recommendations in the most widely consulted therapeutic guidelines in Australia
(Therapeutic Guidelines). DESIGN AND SETTING: Comparison of general practice
activity data for April 2010 - March 2015 (derived from Bettering the Evaluation
and Care of Health [BEACH] study) with estimated rates of prescribing recommended
by Therapeutic Guidelines. MAIN OUTCOME MEASURES: Antibiotic prescribing rates
and estimated guideline-recommended rates per 100 encounters and per full-time
equivalent (FTE) GP per year for eight ARIs; number of prescriptions nationally
per year. RESULTS: An estimated mean 5.97 million (95% CI, 5.69-6.24 million) ARI
cases per year were managed in Australian general practice with at least one
antibiotic, equivalent to an estimated 230 cases per FTE GP/year (95% CI, 219-240
cases/FTE/year). Antibiotics are not recommended by the guidelines for acute
bronchitis/bronchiolitis (current prescribing rate, 85%) or influenza (11%); they
are always recommended for community-acquired pneumonia (current prescribing
rate, 72%) and pertussis (71%); and they are recommended for 0.5-8% of cases of
acute rhinosinusitis (current prescribing rate, 41%), 20-31% of cases of acute
otitis media (89%), and 19-40% cases of acute pharyngitis or tonsillitis (94%).
Had GPs adhered to the guidelines, they would have prescribed antibiotics for
0.65-1.36 million ARIs per year nationally, or at 11-23% of the current
prescribing rate. Antibiotics were prescribed more frequently than recommended
for acute rhinosinusitis, acute bronchitis/bronchiolitis, acute otitis media, and
acute pharyngitis/tonsillitis. CONCLUSIONS: Antibiotics are prescribed for ARIs
at rates 4-9 times as high as those recommended by Therapeutic Guidelines. Our
data provide the basis for setting absolute targets for reducing antibiotic
prescribing in Australian general practice.
PMID- 28701119
TI - Hepatitis C in Australia - a role for general practitioners?
PMID- 28701120
TI - Lessons from Medicare Locals for Primary Health Networks.
PMID- 28701121
TI - Where to next for rural general practice policy and research in Australia?
PMID- 28701122
TI - Iron stain following an intravenous iron infusion.
PMID- 28701123
TI - Not all that wheezes is asthma.
PMID- 28701124
TI - How to perform the ankle brachial index test in clinical practice.
PMID- 28701125
TI - Can antibiotic prescribing for respiratory infections be reduced?
PMID- 28701126
TI - Educating general practitioners: are we preparing them for cost-conscious care?
PMID- 28701127
TI - Changes in pathology test ordering by early career general practitioners: a
longitudinal study.
AB - OBJECTIVE: To assess the number of pathology tests ordered by general practice
registrars during their first 18-24 months of clinical general practice. DESIGN:
Longitudinal analysis of ten rounds of data collection (2010-2014) for the
Registrar Clinical Encounters in Training (ReCEnT) study, an ongoing,
multicentre, cohort study of general practice registrars in Australia. The
principal analysis employed negative binomial regression in a generalised
estimating equations framework (to account for repeated measures on
registrars).Setting, participants: General practice registrars in training posts
with five of 17 general practice regional training providers in five Australian
states. The registrar participation rate was 96.4%. MAIN OUTCOME MEASURE: Number
of pathology tests requested per consultation. The time unit for analysis was the
registrar training term (the 6-month full-time equivalent component of clinical
training); registrars contributed data for up to four training terms. RESULTS:
876 registrars contributed data for 114 584 consultations. The number of
pathology tests requested increased by 11% (95% CI, 8-15%; P < 0.001) per
training term. CONCLUSIONS: Contrary to expectations, pathology test ordering by
general practice registrars increased significantly during their first 2 years of
clinical practice. This causes concerns about overtesting. As established general
practitioners order fewer tests than registrars, test ordering may peak during
late vocational training and early career practice. Registrars need support
during this difficult period in the development of their clinical practice
patterns.
PMID- 28701128
TI - High rates of general practice attendance by former prisoners: a prospective
cohort study.
AB - OBJECTIVES: To determine the rates at which people recently released from prison
attend general practitioners, and to describe service users and their encounters.
DESIGN, PARTICIPANTS AND SETTING: Prospective cohort study of 1190 prisoners in
Queensland, interviewed up to 6 weeks before expected release from custody
(August 2008 - July 2010); their responses were linked prospectively with
Medicare and Pharmaceutical Benefits Scheme data for the 2 years after their
release. General practice attendance was compared with that of members of the
general Queensland population of the same sex and in the same age groups. MAIN
OUTCOME MEASURES: Rates of general practice attendance by former prisoners during
the 2 years following their release from prison. RESULTS: In the 2 years
following release from custody, former prisoners attended general practice
services twice as frequently (standardised rate ratio, 2.04; 95% CI, 2.00-2.07)
as other Queenslanders; 87% of participants visited a GP at least once during
this time. 42% of encounters resulted in a filled prescription, and 12% in
diagnostic testing. Factors associated with higher rates of general practice
attendance included history of risky opiate use (incidence rate ratio [IRR],
2.09; 95% CI, 1.65-2.65), having ever been diagnosed with a mental disorder (IRR,
1.32; 95% CI, 1.14-1.53), and receiving medication while in prison (IRR, 1.82;
95% CI, 1.58-2.10). CONCLUSIONS: Former prisoners visited general practice
services with greater frequency than the general Queensland population. This is
consistent with their complex health needs, and suggests that increasing access
to primary care to improve the health of former prisoners may be insufficient,
and should be accompanied by improving the quality, continuity, and cultural
appropriateness of care.
PMID- 28701129
TI - Iron deficiency and new insights into therapy.
AB - Iron deficiency and iron deficiency anaemia remain prevalent in Australia. The
groups at highest risk are pre-menopausal women, socially disadvantaged people
and those of Indigenous background. Diagnosing iron deficiency using a full blood
examination and iron studies can be difficult and can be further complicated by
concomitant inflammation. Results of iron studies should always be interpreted as
an overall picture rather than focusing on individual parameters. In difficult
clinical scenarios, soluble transferrin receptor assays can be useful. Management
of iron deficiency involves identification and treatment of the cause of iron
deficiency, as well as effective iron replacement. Clinicians should always take
a detailed history and perform a comprehensive physical examination of a patient
with iron deficiency. Patients should be monitored even if a likely cause of iron
deficiency is identified. Patients who fail to respond to iron replacement or
maintain iron status should be referred for further investigation, including
endoscopy to exclude internal bleeding. Both enteral and parenteral iron are
effective at replacing iron. For most adult patients, we recommend trialling
daily oral iron (30-100 mg of elemental iron) as the first-line therapy. Safety
and efficacy of intravenous iron infusions have improved with the availability of
a newer formulation, ferric carboxymaltose. Patients who fail to respond to oral
iron replacement can be safely managed with intravenous iron. Blood transfusion
for iron deficiency anaemia should be reserved for life-threatening situations
and should always be followed by appropriate iron replacement.
PMID- 28701130
TI - Wastewater analysis shows a large decrease in oxycodone use in Adelaide.
PMID- 28701131
TI - Sarcopenia: a potential cause and consequence of type 2 diabetes in Australia's
ageing population?
PMID- 28701132
TI - Sarcopenia: a potential cause and consequence of type 2 diabetes in Australia's
ageing population?
PMID- 28701133
TI - Robotic prostatectomy took off, despite a lack of evidence and risks of inequity.
PMID- 28701134
TI - Robotic prostatectomy took off, despite a lack of evidence and risks of inequity.
PMID- 28701136
TI - Around the universities and research institutes.
PMID- 28701135
TI - State GP of the Year finalists announced.
PMID- 28701137
TI - Editorial: Conventional, Traditional and Alternative Therapies for Cardiovascular
Disorders. Part 3: Alternative Therapy.
PMID- 28701138
TI - Editorial: Antiplatelet and Anticoagulation Treatment in Special Populations.
PMID- 28701139
TI - Editorial: (Pharmaco)Metabolomics in Drug Discovery and Individualisation of
Treatment.
PMID- 28701140
TI - Editorial: Targeting the Brain with Nanomedicine: Diagnostics, Prevention and
Treatment.
PMID- 28701142
TI - INJECTING NANOPARTICLES INTO IMMUNOTHERAPY.
AB - Sarah Webb explores nanoscience strategies for activating T cells in the fight
against cancer.
PMID- 28701141
TI - Editorial: Frontier Views in Designing Therapeutic Candidates for Management of
Diverse Diseases.
PMID- 28701143
TI - SMRT Gate: A method for validation of synthetic constructs on Pacific Biosciences
sequencing platforms.
AB - Current DNA assembly methods are prone to sequence errors, requiring rigorous
quality control (QC) to identify incorrect assemblies or synthesized constructs.
Such errors can lead to misinterpretation of phenotypes. Because of this
intrinsic problem, routine QC analysis is generally performed on three or more
clones using a combination of restriction endonuclease assays, colony PCR, and
Sanger sequencing. However, as new automation methods emerge that enable high
throughput assembly, QC using these techniques has become a major bottleneck.
Here, we describe a quick and affordable methodology for the QC of synthetic
constructs. Our method involves a one-pot digestion-ligation DNA assembly
reaction, based on the Golden Gate assembly methodology, that is coupled with
Pacific Biosciences' Single Molecule, Real-Time (PacBio SMRT) sequencing
technology.
PMID- 28701144
TI - Template-dependent multiple displacement amplification for profiling human
circulating RNA.
AB - Multiple displacement amplification (MDA) is widely used in whole
genome/transcriptome amplification. However, template-independent amplification
(TIA) in MDA is a commonly observed phenomenon, particularly when using high
concentrations of random hexamer primers and extended incubation times. Here, we
demonstrate that the use of random pentamer primers with 5' ends blocked by a C18
spacer results in MDA solely in a template-dependent manner, a technique we have
named tdMDA. Together with an optimized procedure for the removal of residual
genomic DNA during RNA extraction, tdMDA was used to profile circulating RNA from
0.2 mL of patient sera. In comparison to regular MDA, tdMDA demonstrated a lack
of quantifiable DNA amplification in the negative control, a remarkable reduction
of unmapped reads from Illumina sequencing (7 +/- 10.9% versus 58.6 +/- 39%, P =
0.006), and increased mapping rates of the serum transcriptome (26.9 +/- 7.9%
versus 5.8 +/- 8.2%, P = 3.8 * 10-4). Transcriptome profiles could be used to
separate patients with chronic hepatitis C virus (HCV) infection from those with
HCV-associated hepatocellular carcinoma (HCC). We conclude that tdMDA should
facilitate RNA-based liquid biopsy, as well as other genome studies with
biological specimens having ultralow amounts of genetic material.
PMID- 28701145
TI - An in vitro technique to identify the RNA binding-site sequences for RNA-binding
proteins.
AB - RNA-protein interactions play a major role in gene regulation. Although many
techniques to analyze RNA-protein interactions have been developed, noteworthy
challenges such as determining the RNA sequences that bind RNA-binding proteins
(RBPs) remain unsolved. Here, we describe a novel technique using a 4-thio
uridine-incorporated RNA pool to identify the RBP-binding consensus sequences for
RBPs produced by in vitro transcription and translation. To confirm the fidelity
of this approach, we determined the consensus RBP-binding sequence for RBFOX2,
UGC(A/U)(A/U)NU, which is very similar to the known RBFOX2-binding sequence,
UGCAUG. Using our method, consensus RBP-binding sequences were determined for
three RBPs, namely FUS (fused in sarcoma), SFPQ (splicing factor proline and
glutamine rich), and SAM68 (Src-Associated substrate in Mitosis 68 kDa). The
consensus RBP-binding sequences for these RBPs were confirmed by RNA-protein
complex immunoprecipitation-PCR analysis.
PMID- 28701146
TI - Counting nuclei released from microcarrier-based cultures using pro-fluorescent
nucleic acid stains and volumetric flow cytometry.
AB - Counting nuclei released from intact cells is a convenient and reliable approach
to assess cell density during microcarrier-based culture of adherent cells.
However, commonly used methods for counting nuclei, such as crystal violet
staining and quantification with a hemocytometer/automated imaging system or a
Coulter counter, are imprecise, laborious and, limited in throughput. Here, we
describe the use of high-affinity pro-fluorescent nucleic acid stains and
volumetric flow cytometry for automated counting of nuclei released from cells
attached to microcarriers with improved precision and high sample throughput.
This simple procedure facilitates rapid and precise assessment of cell
attachment, survival, and proliferation on microcarriers, and can provide
information about the cell cycle, all without the need for cell detachment.
Consequently, various microcarrier-based applications, from small-scale multi
factor experiments to large-scale functional genetic screens and
clinical/industrial cultures, could be enhanced by this approach.
PMID- 28701147
TI - Combinational use of lipid-based reagents for efficient transfection of primary
fibroblasts and hepatoblasts.
AB - Commercially available lipid-based transfection reagents are widely used to
deliver DNA to cells. However, these lipid-based transfection reagents show poor
gene transfer efficiency in primary cells. Here, we demonstrate a simple method
to improve gene transfer efficiency in primary fibroblasts and hepatoblasts using
a combination of lipid-based transfection reagents. Our data show that combined
use of Lipofectamine LTX and FuGENE HD increases the efficiency of gene transfer
compared with the use of either reagent alone, and this combination achieves the
best result of any pairwise combination of Lipofectamine LTX, FuGENE HD,
TransFectin, and Fibroblast Transfection Reagent.
PMID- 28701149
TI - The prevalence of gastric heterotopia of the proximal esophagus is
underestimated, but preneoplasia is rare - correlation with Barrett's esophagus.
AB - BACKGROUND: The previously reported prevalence of gastric heterotopia in the
cervical esophagus, also termed inlet patch (IP), varies substantially, ranging
from 0.18 to 14%. Regarding cases with adenocarcinoma within IP, some experts
recommend to routinely obtain biopsies from IP for histopathology. Another
concern is the reported relation to Barrett's esophagus. The objectives of the
study were to prospectively determine the prevalence of IP and of preneoplasia
within IP, and to investigate the association between IP and Barrett's esophagus.
METHODS: 372 consecutive patients undergoing esophagogastroduodenoscopy were
carefully searched for the presence of IP. Biopsies for histopathology were
targeted to the IP, columnar metaplasia of the lower esophagus, gastric corpus
and antrum. Different definitions of Barrett's esophagus were tested for an
association with IP. RESULTS: At least one IP was endoscopically identified in 53
patients (14.5%). Histopathology, performed in 46 patients, confirmed columnar
epithelium in 87% of cases, which essentially presented corpus and/or cardia-type
mucosa. Intestinal metaplasia was detected in two cases, but no neoplasia. A
previously reported association of IP with Barrett's esophagus was weak,
statistically significant only when short segments of cardia-type mucosa of the
lower esophagus were included in the definition of Barrett's esophagus.
CONCLUSIONS: The prevalence of IP seems to be underestimated, but preneoplasia
within IP is rare, which does not support the recommendation to regularly obtain
biopsies for histopathology. Biopsies should be targeted to any irregularities
within the heterotopic mucosa. The correlation of IP with Barrett's esophagus
hints to a partly common pathogenesis.
PMID- 28701150
TI - Physiological roles of sigma factor SigD in Corynebacterium glutamicum.
AB - BACKGROUND: Sigma factors are one of the components of RNA polymerase
holoenzymes, and an essential factor of transcription initiation in bacteria.
Corynebacterium glutamicum possesses seven genes coding for sigma factors, most
of which have been studied to some detail; however, the role of SigD in
transcriptional regulation in C. glutamicum has been mostly unknown. RESULTS: In
this work, pleiotropic effects of sigD overexpression at the level of phenotype,
transcripts, proteins and metabolites were investigated. Overexpression of sigD
decreased the growth rate of C. glutamicum cultures, and induced several
physiological effects such as reduced culture foaming, turbid supernatant and
cell aggregation. Upon overexpression of sigD, the level of Cmt1 (corynomycolyl
transferase) in the supernatant was notably enhanced, and carbohydrate-containing
compounds were excreted to the supernatant. The real-time PCR analysis revealed
that sigD overexpression increased the expression of genes related to
corynomycolic acid synthesis (fadD2, pks), genes encoding corynomycolyl
transferases (cop1, cmt1, cmt2, cmt3), L, D-transpeptidase (lppS), a subunit of
the major cell wall channel (porH), and the envelope lipid regulation factor
(elrF). Furthermore, overexpression of sigD resulted in trehalose
dicorynomycolate accumulation in the cell envelope. CONCLUSIONS: This study
demonstrated that SigD regulates the synthesis of corynomycolate and related
compounds, and expanded the knowledge of regulatory functions of sigma factors in
C. glutamicum.
PMID- 28701151
TI - Mother's education and the risk of several neonatal outcomes: an evidence from an
Italian population-based study.
AB - BACKGROUND: Maternal socioeconomic disparities strongly affect child health,
particularly in low and middle income countries. We assessed whether neonatal
outcomes varied by maternal education in a setting where healthcare system
provides universal coverage of health services to all women, irrespective of
their socioeconomic status. METHODS: A population-based study was performed on
383,103 singleton live births occurring from 2005 to 2010 in Lombardy, an Italian
region with approximately 10 million inhabitants. The association between
maternal education, birthplace and selected neonatal outcomes (preterm birth, low
birth weight, small-for-gestational age, low 5-min Apgar score, severe congenital
anomalies, cerebral distress and respiratory distress) was estimated by fitting
logistic regression models. Model adjustments were applied for sociodemographic,
reproductive and medical maternal traits. RESULTS: Compared with low-level
educated mothers, those with high education had reduced odds of preterm birth
(Odds Ratio; OR = 0.81, 95% CI 0.77-0.85), low birth weight (OR = 0.78, 95% CI
0.70-0.81), small for gestational age (OR = 0.82, 95% CI 0.79-0.85), and
respiratory distress (OR = 0.84, 95% CI 0.80-0.88). Mothers born in a foreign
country had higher odds of preterm birth (OR = 1.16, 95% CI 1.11-1.20), low Apgar
score (OR = 1.18, 95% CI 1.07-1.30) and respiratory distress (OR = 1.19, 95% CI
1.15-1.24) than Italian-born mothers. The influence of maternal education on
neonatal outcomes was confirmed among both, Italian-born and foreign-born
mothers. CONCLUSIONS: Low levels of education and maternal birthplace are
important factors associated with adverse neonatal outcomes in Italy. Future
studies are encouraged to investigate factors mediating the effects of
socioeconomic inequality for identifying the main target groups for
interventions.
PMID- 28701152
TI - Performance of urinary neutrophil gelatinase-associated lipocalin, clusterin, and
cystatin C in predicting diabetic kidney disease and diabetic microalbuminuria: a
consecutive cohort study.
AB - BACKGROUND: Tubular biomarkers have been regarded as emerging and promising
markers for early diagnosis of diabetic kidney disease (DKD). The study was to
determine the diagnostic capabilities of tubular biomarkers (urinary neutrophil
gelatinase-associated lipocalin [NGAL], clusterin, and cystatin C) for DKD and
diabetic microalbuminuria, and whether or not the tubular biomarkers appear
earlier than microalbuminuria. METHODS: In this consecutive cohort study, 146
type 2 diabetes mellitus (T2DM) patients with a disease duration of >=6 years
were enrolled. Thirty age- and gender-matched subjects without any systemic
diseases were recruited as the control group. Urinary samples collected before
treatment were tested for NGAL, clusterin, and cystatin C. RESULTS: The levels of
biomarkers were higher in patients with DKD (p < 0.001); and positively
correlated with the urinary albumin creatinine ratio (UACR; p < 0.001). With
respect to the diagnosis of DKD, the areas under the receiver operating
characteristic curve (AUCs) for urinary NGAL, clusterin, and cystatin C were
0.816 (95% confidence interval [CI], 0.741-0.891), 0.775 (95% CI: 0.694-0.857),
and 0.803 (95% CI: 0.722-0.884), respectively. The levels of urinary NGAL and
cystatin C in the normoalbuminuria group (UACR <30 mg /g*Cr) were elevated
compared with the control group, unlike urinary clusterin. There was no
statistical difference in the levels of the three biomarkers between groups with
different levels of haemoglobin A1C (HbA1c). The diagnostic AUCs for urinary
NGAL, clusterin, and cystatin C in patients with diabetic microalbuminuria were
0.841 (95% CI: 0.775-0.907), 0.783(95% CI: 0.710-0.856), and 0.805 (95% CI: 0.733
0.877), respectively. CONCLUSIONS: Urinary NGAL, clusterin, and cystatin C may be
promising biomarkers for diagnosing DKD and diabetic microalbuminuria. It is
possible that urinary NGAL and cystatin C increase before the onset of
microalbuminuria in T2DM patients.
PMID- 28701153
TI - Cost-effectiveness of an ambulance-based referral system for emergency
obstetrical and neonatal care in rural Ethiopia.
AB - BACKGROUND: To estimate the cost-effectiveness of an ambulance-based referral
system an dedicated to emergency obstetrics and neonatal care (EmONC) in remote
sub-Saharan settings. METHODS: In this prospective study performed in Oromiya
Region (Ethiopia), all obstetrical cases referred to the hospital with the
ambulance were consecutively evaluated during a three-months period. The health
professionals who managed the referred cases were requested to identify those
that could be considered as undoubtedly effective. Pre and post-referral costs
included those required to run the ambulance service and the additional costs
necessary for the assistance in the hospital. Local life expectancy tables were
used to calculate the number of year saved. RESULTS: A total of 111 ambulance
referrals were recorded. The ambulance was undoubtedly effective for 9 women and
4 newborns, corresponding to 336 years saved. The total cost of the intervention
was 8299 US dollars. The cost per year life saved was 24.7 US dollars which is
below the benchmarks of 150 and 30 US dollars that define attractive and very
attractive interventions. Sensitivity analyses on the rate of effective
referrals, on the costs of the ambulance and on the discount rate confirmed the
robustness of the result. CONCLUSIONS: An ambulance-based referral system for
EmONC in remote sub-Saharan areas appears highly cost-effective.
PMID- 28701154
TI - Long-term effects and psychological adjustment: study protocol of a large
register-based study on quality of life among survivors of hematological
malignancies.
AB - BACKGROUND: Both incidence and survival rates of hematological cancers are
increasing, leading to a growing number of survivors with specific late and long
term effects. However, relevant research in physical, psychological and social
aspects of quality of life is scarce. Existing literature shows that a
considerable number of cancer survivors report a relatively high quality of life
despite a variety of adverse and persistent symptoms. To date, the reasons for
this phenomenon as well as moderating and mediating factors are widely unknown.
Given these research gaps, we aim to investigate the different domains of quality
of life among long-term survivors of hematological cancers and to identify
factors predicting high quality of life. METHODS/DESIGN: This is a large cross
sectional study among hematological cancer survivors at a minimum of 3 years
after diagnosis. We will collect 1000 survivors completing a set of self-report
questionnaires encompassing physical, psychological and social domains of quality
of life. Participants are clustered in groups according to time since diagnosis
and compared with each other. Furthermore, survivors will be compared with the
general population. Factors predicting high quality of life will be identified
via multiple regression analyses and structure equation modeling. DISCUSSION: Our
study will help to inform health care providers about the specific long-term
burden among survivors with hematological malignancies. Identification of factors
predicting high quality of life will help to develop adequate intervention
strategies to enhance well-being in hematological cancer survivors. Our
methodological advantages including the large sample as well as the assessment of
different domains of quality of life will ensure novel and robust results. A
limitation of the study is the cross-sectional design.
PMID- 28701155
TI - Maternal obesity and its effect on labour duration in nulliparous women: a
retrospective observational cohort study.
AB - BACKGROUND: Obesity is increasing among primipara women. We aimed to describe the
association between body mass index (BMI) during early-pregnancy and duration of
labour in nulliparous women. METHODS: Retrospective observational cohort study of
1885 nulliparous women with a single cephalic presentation from 37 0/7 to 42 6/7
weeks of completed gestation and spontaneous or induced labour at Nordsjaellands
Hospital, University of Copenhagen, Denmark, in 2011 and 2012. Total duration of
labour and the first and second stages of labour were compared between early
pregnancy normal-weight (BMI <25 kg/m2), overweight (BMI 25-29.9 kg/m2), and
obese (BMI >=30 kg/m2) women. Proportional hazards and multiple logistic
regression models were applied. RESULTS: Early pregnancy BMI classified 1246
(66.1%) women as normal weight, 350 (18.6%) as overweight and 203 (10.8%) as
obese. No difference in the duration of total or first stage of active labour was
found for overweight (adjusted HR = 1.01, 95% CI 0.88-1.16) or obese (adjusted HR
= 1.07, 95% CI 0.90-1.28) compared to normal weight women. Median active labour
duration was 5.83 h for normal weight, 6.08 h for overweight and 5.90 h for obese
women. The risk of caesarean delivery increased significantly for overweight and
obese compared to normal weight women (odds ratios (OR) 1.62; 95%CI 1.18-2.22 and
1.76; 95%CI 1.20-2.58, respectively). Caesarean deliveries were performed earlier
in labour in obese than normal-weight women (HR = 1.80, 95%CI 1.28-2.54).
CONCLUSION: BMI had no significant effect on total duration of active labour.
Risk of caesarean delivery increased with increasing BMI. Caesarean deliveries
are undertaken earlier in obese women compared to normal weight women following
the onset of active labour, shortening the total duration of active labour.
PMID- 28701156
TI - The current level of shared decision-making in anesthesiology: an exploratory
study.
AB - BACKGROUND: Shared decision-making (SDM) seeks to involve both patients and
clinicians in decision-making about possible health management strategies, using
patients' preferences and best available evidence. SDM seems readily applicable
in anesthesiology. We aimed to determine the current level of SDM among
preoperative patients and anesthesiology clinicians. METHODS: We invited 115
consecutive preoperative patients, visiting the pre-assessment outpatient clinic
of the department of Anesthesiology at the Academic Medical Center of Amsterdam.
Inclusion criteria were patients who needed surgery in the arms, lower abdomen or
legs, and in whom three anesthesia techniques were feasible. The SDM-level of the
consultation was scored objectively by independent observers who judged audio
recordings of the consultation using the OPTION5-scale, ranging from 0% (no SDM)
to 100% (optimum SDM), as well as subjectively by patients (using the SDM-Q-9 and
CollaboRATE questionnaires) and clinicians (SDM-Q-Doc questionnaire). Objective
and subjective SDM-levels were assessed on five-point and six-point Likert
scales, respectively. Both scores were expressed as percentages. RESULTS: Data of
80 patients could be analysed. Objective SDM-scores were low (30.5%). Subjective
scores of the SDM-Q-9 and CollaboRATE were high among patients (91.7% and 96.3%,
respectively) and among clinicians (SDM-Q-Doc; 84.3%). Apparently, they
appreciated satisfaction rather than SDM, being poorly aware of what SDM entails.
CONCLUSION: The level of SDM in an outpatient anesthesiology clinic where
preoperative patients receive information about various possible anesthesia
options, was found to be low. Thus, there is room for improving the level of SDM.
Some suggestions are given how this can be achieved.
PMID- 28701157
TI - Dacin, one metalloproteinase from Deinagkistrodon acutus venom inhibiting
contraction of mouse ileum muscle.
AB - BACKGROUND: Mice were bitten by five-pace vipers (Deinagkistrodon acutus), and
then envenomed. It was well-known that the snake venom mainly disturbed the blood
homeostasis of the envenomed victims. Ocassionally, we found that the venom of D.
acutus could inhibit the contraction tension of mouse ileum, so in this study we
aimed to identify the active component inhibiting the contraction tension of
mouse ileum in the snake venom. RESULTS: The active component inhibiting the
contraction tension of mouse ileum, designated as Dacin, was isolated from D.
acutus venom, purified to protein homogeneity and composed of a single peptide
chain, about 23 kDa analyzed by SDS-PAGE, and 22, 947. 9 Da measured by MALDI-TOF
MS. Not only the results of its PMF blasted by Mascot indicated that Dacin may be
one snake venom metalloproteinase (SVMP), but also the results of the biochemical
and in-vivo assays as follow demonstrated that it was one SVMP: it cleaved Aalpha
and Bbeta chains, not Cgamma of bovine fibrinogen within 1 h, and also hydrolyzed
fibrin polymer; besides its fibrino(geno)lytic activities were strongly inhibited
by beta- mercaptoethanol, EDTA and EGTA; and it could induce a hemorrhagic
reaction under the dorsal skin of mouse. In the isolated tissue assays, Dacin
caused the concentration-dependent and time-dependent inhibitory actions on the
spontaneous contraction tension of the ileum smooth muscle of mouse, and the
inhibitory effects were irreversible. CONCLUSIONS: Taken together, for the first
time one active component (Dacin, a SVMP) that irreversibly inhibited the
spontaneous contraction tension of mouse ileum has been isolated and identified
from D. acutus venom. The findings may provide not only a new insight for
toxicological researches on SVMPs and venoms of the vipers, but also a reference
for clinicians to treat the snake-bitten victims. However, Dacin's inhibitory
molecular mechanism will be further studied in the future.
PMID- 28701158
TI - Endotoxemia is associated with acute coronary syndrome in patients with end stage
kidney disease.
AB - BACKGROUND: Cardiovascular disease is the major cause of death in patients with
end-staged kidney disease (ESRD). Most ESRD patients have systemic inflammation,
and increasing the risk of cardiovascular event. Endotoxin derived from
lipopolysaccharide of Gram negative bacteria accounts for 70% of intestinal
bacteria, leading to release of proinflammatory cytokines and negative
cardiovascular effect. Impaired intestinal barriers have been found in some ESRD
patients, and may lead to bacteria translocation from gastrointestinal tract. We
aim to investigate the association of endotoxemia in ESRD patients and acute
coronary syndrome (ACS). METHODS: We collected serum from adult ESRD patients who
presented to emergency department (ED) with ACS (30 patients) or without ACS (30
patients) as control from 11/01/2013 to 10/31/2014 in Chi Mei Medical Center in
southern Taiwan. Clinical information and lab data were collected. We measured
the endotoxin level of the serum of ESRD patients with or without ACS. We used
real-time 16S rDNA PCR to detect possible bacteria in the blood of the patients.
RESULTS: The endotoxin level of ESRD patients with ACS (0.49 (+/-0.12) EU/mL) was
significantly higher than that of ESRD patients without ACS (0.1 +/- 0.08) (p <
0.01). However, the endotoxin level was not correlated with the troponin-I level
(r = -0.12). Although endotoxin level was higher in ESRD patients with ACS,
bacteria were not detected in the serum by using the real-time 16S rDNA PCR.
CONCLUSION: Endotoxin in ESRD patients with ACS was significantly higher than
that without ACS. The result suggested that endotoxemia may have a contributory
role to cardiovascular disease in ESRD patients.
PMID- 28701159
TI - Bacterial bloodstream infections in a tertiary infectious diseases hospital in
Northern Vietnam: aetiology, drug resistance, and treatment outcome.
AB - BACKGROUND: Bloodstream infections (BSIs) are associated with high morbidity and
mortality worldwide. However their aetiology, antimicrobial susceptibilities and
associated outcomes differ between developed and developing countries. Systematic
data from Vietnam are scarce. Here we present aetiologic data on BSI in adults
admitted to a large tertiary referral hospital for infectious diseases in Hanoi,
Vietnam. METHODS: A retrospective study was conducted at the National Hospital
for Tropical Diseases between January 2011 and December 2013. Cases of BSI were
determined from records in the microbiology department. Case records were
obtained where possible and clinical findings, treatment and outcome were
recorded. BSI were classified as community acquired if the blood sample was drawn
<=48 h after hospitalization or hospital acquired if >48 h. RESULTS: A total of
738 patients with BSI were included for microbiological analysis. The predominant
pathogens were: Klebsiella pneumoniae (17.5%), Escherichia coli (17.3%),
Staphylococcus aureus (14.9%), Stenotrophomonas maltophilia (9.6%) and
Streptococcus suis (7.6%). The overall proportion of extended spectrum beta
lactamase (ESBL) production among Enterobacteriaceae was 25.1% (67/267 isolates)
and of methicillin-resistance in S. aureus (MRSA) 37% (40/108). Clinical data was
retrieved for 477 (64.6%) patients; median age was 48 years (IQR 36-60) with
27.7% female. The overall case fatality rate was 28.9% and the highest case
fatality was associated with Enterobacteriaceae BSI (34.7%) which accounted for
61.6% of all BSI fatalities. CONCLUSIONS: Enterobacteriaceae (predominantly K.
pneumoniae and E. coli) are the most common cause of both community and hospital
acquired bloodstream infections in a tertiary referral clinic in northern
Vietnam.
PMID- 28701160
TI - Infants hospitalized for Bordetella pertussis infection commonly have respiratory
viral coinfections.
AB - BACKGROUND: Whether viral coinfections cause more severe disease than Bordetella
pertussis (B. pertussis) alone remainsunclear. We compared clinical disease
severity and sought clinical and demographic differences between infants with B.
pertussis infection alone and those with respiratory viral coinfections. We also
analyzed how respiratory infections were distributed during the 2 years study.
METHODS: We enrolled 53 infants with pertussis younger than 180 days (median age
58 days, range 17-109 days, 64.1% boys), hospitalized in the Pediatric
Departments at "Sapienza" University Rome and Bambino Gesu Children's Hospital
from August 2012 to November 2014. We tested in naso-pharyngeal washings B.
pertussis and 14 respiratory viruses with real-time reverse-transcriptase
polymerase chain reaction. Clinical data were obtained from hospital records and
demographic characteristics collected using a structured questionnaire. RESULTS:
28/53 infants had B. pertussis alone and 25 viral coinfection: 10 human
rhinovirus (9 alone and 1 in coinfectionwith parainfluenza virus), 3 human
coronavirus, 2 respiratory syncytial virus. No differences were observed in
clinical disease severity between infants with B. pertussis infection alone and
those with coinfections. Infants with B. pertussis alone were younger than
infants with coinfections, and less often breastfeed at admission. CONCLUSIONS:
In this descriptive study, no associations between clinical severity and
pertussis with or withoutco-infections were found. TRIAL REGISTRATION:
Policlinico Umberto I: protocol 213/14, 3085/13.02.2014, retrospectively
registered.Bambino Gesu Children's Hospital: protocol n. RF-2010-2317709.
PMID- 28701161
TI - Podiatry intervention versus usual care to prevent falls in care homes: pilot
randomised controlled trial (the PIRFECT study).
AB - BACKGROUND: Common foot problems are independent risk factors for falls in older
people. There is evidence that podiatry can prevent falls in community-dwelling
populations. The feasibility of implementing a podiatry intervention and trial in
the care home population is unknown. To inform a potential future definitive
trial, we performed a pilot randomised controlled trial to assess: (i) the
feasibility of a trial of a podiatry intervention to reduce care home falls, and
(ii) the potential direction and magnitude of the effect of the intervention in
terms of number of falls in care home residents. METHODS: Informed by Medical
Research Council guidance on developing and evaluating complex interventions, we
conducted a single blind, pilot randomised controlled trial in six care homes in
the East of Scotland. Participants were randomised to either: (i) a three month
podiatry intervention comprising core podiatry care, foot and ankle exercises,
orthoses and footwear provision or (ii) usual care. Falls-related outcomes
(number of falls, time to first fall) and feasibility-related outcomes
(recruitment, retention, adherence, data collection rates) were collected.
Secondary outcomes included: generic health status, balance, mobility, falls
efficacy, and ankle joint strength. RESULTS: 474 care home residents were
screened. 43 (9.1%) participants were recruited: 23 to the intervention, 20 to
control. Nine (21%) participants were lost to follow-up due to declining health
or death. It was feasible to deliver the trial elements in the care home setting.
35% of participants completed the exercise programme. 48% reported using the
orthoses 'all or most of the time'. Completion rates of the outcome measures were
between 93% and 100%. No adverse events were reported. At the nine month follow
up period, the intervention group per-person fall rate was 0.77 falls vs. 0.83
falls in the control group. CONCLUSIONS: A podiatry intervention to reduce falls
can be delivered to care home residents within a pilot randomised controlled
trial of the intervention. Although not powered to determine effectiveness, these
preliminary data provide justification for a larger trial, incorporating a full
process evaluation, to determine whether this intervention can significantly
reduce falls in this high-risk population. TRIAL REGISTRATION: ClinicalTrials.gov
identifier: NCT02178527 ; Date of registration: 17 June 2014.
PMID- 28701162
TI - Does the ingestion of a 24 hour low glycaemic index Asian mixed meal diet improve
glycaemic response and promote fat oxidation? A controlled, randomized cross-over
study.
AB - BACKGROUND: The health benefits of consuming a low glycaemic index (GI) diet to
reduce the risk of type 2 Diabetes are well recognized. In recent years the GI
values of various foods have been determined. Their efficacy in constructing and
consuming a low GI diet over 24 h in modulating glycaemic response has not been
fully documented. The translation of using single-point GI values of foods to
develop a 24 h mixed meal diet can provide valuable information to consumers,
researchers and dietitians to optimize food choice for glycaemic control. By
using GI values of foods to develop mixed meals, our study is the first to
determine how both blood glucose and substrate oxidation may be modulated over 24
h. METHODS: The study included 11 Asian men with a BMI between 17-24 kg/m2 who
followed both a 1-day low GI and 1-day high GI diet in a randomized, controlled
cross-over design. Test meals included breakfast, lunch, snack and dinner.
Glycaemic response was measured continuously for over 24 h and postprandial
substrate oxidation for 10 h inside a whole body calorimeter. RESULTS: The low GI
diet resulted in lower 24 h glucose iAUC (860 +/- 440 vs 1329 +/- 614 mmol/L.min;
p = 0.014) with lower postprandial glucose iAUC after breakfast (p < 0.001),
lunch (p = 0.009), snack (p = 0.012) and dinner (p = 0.003). Moreover, 24 h mean
amplitude of glycaemic excursion was lower during the low GI vs high GI diet
(1.44 +/- 0.63 vs 2.33 +/- 0.82 mmol/L; p < 0.001). Simultaneously, decrease in
10 h fat oxidation was less during the low vs high GI diet (-0.033 +/- 0.021 vs
0.050 +/- 0.017 g/min; p < 0.001), specifically after breakfast (p < 0.001) and
lunch (p < 0.001). CONCLUSIONS: Our study corroborates that using low GI local
foods to construct a 24 h low GI diet, is able to reduce glycaemic response and
variability as recorded by continuous glucose monitoring. Our observations also
confirm that a low GI diet promotes fat oxidation over carbohydrate oxidation
when compared to a high GI diet. These observations provide public health support
for the encouragement of healthier nutrition choices by consuming low GI foods.
TRIAL REGISTRATION: NCT 02631083 (Clinicaltrials.gov).
PMID- 28701163
TI - Quality of life and general health of infertile women.
AB - BACKGROUND: Measuring the quality of life (QOL) is a benchmark in today's world
of medicine. The aim of the present study was to determine the general health and
QOL of infertile women and certain affecting conditions. METHODS: In a cross
sectional study, 161 infertile women referring to Dr. Rostami's Infertility
Center of Shiraz, Southern Iran, in 2013 were enrolled by the convenience
sampling method. Data were collected via a socio-demographic, general health
(GHQ28), and the QOL Questionnaire of Infertile Couples and analyzed using
descriptive and analytical statistics. RESULTS: According to 146 completely
filled-out questionnaires, the mean age of the participants and their spouses
were 29.4 +/- 5.4 and 33.8 +/- 5.8 years, respectively. Moreover, the general
health of 57 (39%) patients was normal and that of 89 (61%) patients showed a
degree of impairment. The scores for depression and physical symptoms were the
highest and lowest, respectively. In addition, quite positive, positive, neutral,
and negative specific QOL of infertile women were detected in 4 (2.8%), 72
(49.3%), 70 (47.9%), and 0 (0%) individuals, respectively. The total QOL scores
had maximum correlation with GHQ anxiety (r = -0.596, P < 0.001) and general
health scores had the highest correlation with physical QOL (r = -0.637, P <
0.001). The QOL was economically (P = 0.027), emotionally (P = 0.004), sexually
(P = 0.017), physically (P = 0.037), and psychologically (P = 0.001) less for the
women living in rural areas than other infertile women. However, university
education (P = 0.015) and higher income per month (P = 0.008) had positive
associations with QOL. CONCLUSION: General health of more than half of the
infertile women indicated a degree of disorder. These women face the risk of
anxiety, social dysfunction, and depression. Educational status, monthly income,
and rural/urban residency are the major factors influencing the QOL.
PMID- 28701165
TI - Ethnomedicinal and cultural practices of mammals and birds in the vicinity of
river Chenab, Punjab-Pakistan.
AB - BACKGROUND: Although, use of animal species in disease treatment and culture
practices is as ancient as that of plant species; however ethnomedicinal uses and
cultural values of animal species have rarely been reported. Present study is the
first report on the medicinal uses of mammals and bird species in Pakistan.
METHODS: Questionnaires and semi-structured interviews were applied to collect
qualitative and quantitative data from local informants (N = 109). Relative
frequency of mention (RFM), fidelity level (FL), relative popularity level (RPL),
similarity index (SI) and rank order priority (ROP) indices were used to analyzed
the data. RESULTS: One hundred and eight species of animals, which include: 83%
birds and 17% mammals were documented. In total 30 mammalian and 28 birds'
species were used to treat various diseases such as rheumatic disorders, skin
infections and sexual weakness among several others. Fats, flesh, blood, milk and
eggs were the most commonly utilized body parts. Bos taurus, Bubalus bubalis,
Capra aegagrus hircus, Felis domesticus, Lepus nigricollis dayanus and Ovis aries
(mammals) and Anas platyrhynchos domesticus, Columba livia, Coturnix coturnix,
Gallus gallus and Passer domesticus (birds) were the highly utilized species.
Medicinal and cultural uses of 30% mammals and 46% birds were reported for the
first time, whereas 33% mammals and 79% birds depicted zero similarity with
previous reports. CONCLUSION: Present study exhibits significant ethnozoological
knowledge of local inhabitants and their strong association with animal species,
which could be helpful in sustainable use of biodiversity of the region.
Additionally, in vitro and in vivo evaluation of biological activities in the
mammalian and birds' species with maximum fidelity level and frequency of mention
could be important to discover animal based novel drugs. Some commonly used
mammals and birds species of the study area.
PMID- 28701164
TI - Effects from a 90-day inhalation toxicity study with cerium oxide and barium
sulfate nanoparticles in rats.
AB - BACKGROUND: Nanomaterials like cerium oxide and barium sulfate are frequently
processed in industrial and consumer products and exposure of humans and other
organisms is likely. Generally less information is given on health effects and
toxicity, especially regarding long-term exposure to low nanoparticle doses.
Since inhalation is still the major route of uptake the present study focused on
pulmonary effects of CeO2NM-212 (0.1, 0.3, 1.0, 3.0 mg/m3) and BaSO4NM-220
nanoparticles (50.0 mg/m3) in a 90-day exposure setup. To define particle-related
effects and potential mechanisms of action, observations in histopathology,
bronchoalveolar lavage and immunohistochemistry were linked to pulmonary
deposition and clearance rates. This further allows evaluation of potential
overload related effects. RESULTS: Lung burden values increased with increasing
nanoparticle dose levels and ongoing exposure. At higher doses, cerium clearance
was impaired, suggesting lung overload. Barium elimination was extremely rapid
and without any signs of overload. Bronchoalveolar lavage fluid analysis and
histopathology revealed lung tissue inflammation with increasing severity and
post-exposure persistency for CeO2. Also, marker levels for genotoxicity and cell
proliferation were significantly increased. BaSO4 showed less inflammation or
persistency of effects and particularly affected the nasal cavity. CONCLUSION:
CeO2 nanoparticles penetrate the alveolar space and affect the respiratory tract
after inhalation mainly in terms of inflammation. Effects at low dose levels and
post-exposure persistency suggest potential long-term effects and a notable
relevance for human health. The generated data might be useful to improve
nanoparticle risk assessment and threshold value generation. Mechanistic
investigations at conditions of non-overload and absent inflammation should be
further investigated in future studies.
PMID- 28701166
TI - Which early life events or current environmental and lifestyle factors influence
lung function in adolescents? - results from the GINIplus & LISAplus studies.
AB - BACKGROUND: Various factors may affect lung function at different stages in life.
Since investigations that simultaneously consider several factors are rare, we
examined the relative importance of early life, current environmental/lifestyle
factors and allergic diseases on lung function in 15-year-olds. METHODS: Best
subset selection was performed for linear regression models to investigate
associations between 21 diverse early life events and current factors with
spirometric parameters (forced vital capacity, forced expiratory volume in 1 s
and maximal mid-expiratory flow (FEF25-75)) in 1326 participants of the German
GINIplus and LISAplus birth cohorts. To reduce model complexity, one model for
each spirometric parameter was replicated 1000 times in random subpopulations (N
= 884). Only those factors that were included in >70% of the replication models
were retained in the final analysis. RESULTS: A higher peak weight velocity and
early lung infections were the early life events prevalently associated with
airflow limitation and FEF25-75. Current environmental/lifestyle factors at age
15 years and allergic diseases that were associated with lung function were:
indoor second-hand smoke exposure, vitamin D concentration, body mass index (BMI)
and asthma status. Sex and height captured the majority of the explained variance
(>75%), followed by BMI (<=23.7%). The variance explained by early life events
was comparatively low (median: 4.8%; range: 0.2-22.4%), but these events were
consistently negatively associated with airway function. CONCLUSIONS: Although
the explained variance was mainly captured by well-known factors included in lung
function prediction equations, our findings indicate early life and current
factors that should be considered in studies on lung health among adolescents.
PMID- 28701167
TI - A combined experimental and numerical study on upper airway dosimetry of inhaled
nanoparticles from an electrical discharge machine shop.
AB - BACKGROUNDS: Exposure to nanoparticles in the workplace is a health concern to
occupational workers with increased risk of developing respiratory,
cardiovascular, and neurological disorders. Based on animal inhalation study and
human lung tumor risk extrapolation, current authoritative recommendations on
exposure limits are either on total mass or number concentrations. Effects of
particle size distribution and the implication to regional airway dosages are not
elaborated. METHODS: Real time production of particle concentration and size
distribution in the range from 5.52 to 98.2 nm were recorded in a wire-cut
electrical discharge machine shop (WEDM) during a typical working day. Under the
realistic exposure condition, human inhalation simulations were performed in a
physiologically realistic nasal and upper airway replica. The combined
experimental and numerical study is the first to establish a realistic exposure
condition, and under which, detailed dose metric studies can be performed. In
addition to mass concentration guided exposure limit, inhalation risks to nano
pollutant were reexamined accounting for the actual particle size distribution
and deposition statistics. Detailed dosimetries of the inhaled nano-pollutants in
human nasal and upper airways with respect to particle number, mass and surface
area were discussed, and empirical equations were developed. RESULTS: An
astonishing enhancement of human airway dosages were detected by current combined
experimental and numerical study in the WEDM machine shop. Up to 33 folds in
mass, 27 folds in surface area and 8 folds in number dosages were detected during
working hours in comparison to the background dosimetry measured at midnight. The
real time particle concentration measurement showed substantial emission of nano
pollutants by WEDM machining activity, and the combined experimental and
numerical study provided extraordinary details on human inhalation dosimetry. It
was found out that human inhalation dosimetry was extremely sensitive to real
time particle concentration and size distribution. Averaged particle
concentration over 24-h period will inevitably misrepresent the sensible
information critical for realistic inhalation risk assessment. CONCLUSIONS:
Particle size distribution carries very important information in determining
human airway dosimetry. A pure number or mass concentration recommendation on the
exposure limit at workplace is insufficient. A particle size distribution,
together with the deposition equations, is critical to recognize the actual
exposure risks. In addition, human airway dosimetry in number, mass and surface
area varies significantly. A complete inhalation risk assessment requires the
knowledge of toxicity mechanisms in response to each individual metric. Further
improvements in these areas are needed.
PMID- 28701168
TI - Erratum to: Ethics review of studies during public health emergencies - the
experience of the WHO ethics review committee during the Ebola virus disease
epidemic.
PMID- 28701169
TI - Comparison between sEMG and force as control interfaces to support planar arm
movements in adults with Duchenne: a feasibility study.
AB - BACKGROUND: Adults with Duchenne muscular dystrophy (DMD) can benefit from
devices that actively support their arm function. A critical component of such
devices is the control interface as it is responsible for the human-machine
interaction. Our previous work indicated that surface electromyography (sEMG) and
force-based control with active gravity and joint-stiffness compensation were
feasible solutions for the support of elbow movements (one degree of freedom). In
this paper, we extend the evaluation of sEMG- and force-based control interfaces
to simultaneous and proportional control of planar arm movements (two degrees of
freedom). METHODS: Three men with DMD (18-23 years-old) with different levels of
arm function (i.e. Brooke scores of 4, 5 and 6) performed a series of line
tracing tasks over a tabletop surface using an experimental active arm support.
The arm movements were controlled using three control methods: sEMG-based
control, force-based control with stiffness compensation (FSC), and force-based
control with no compensation (FNC). The movement performance was evaluated in
terms of percentage of task completion, tracing error, smoothness and speed.
RESULTS: For subject S1 (Brooke 4) FNC was the preferred method and performed
better than FSC and sEMG. FNC was not usable for subject S2 (Brooke 5) and S3
(Brooke 6). Subject S2 presented significantly lower movement speed with sEMG
than with FSC, yet he preferred sEMG since FSC was perceived to be too fatiguing.
Subject S3 could not successfully use neither of the two force-based control
methods, while with sEMG he could reach almost his entire workspace. CONCLUSIONS:
Movement performance and subjective preference of the three control methods
differed with the level of arm function of the participants. Our results indicate
that all three control methods have to be considered in real applications, as
they present complementary advantages and disadvantages. The fact that the two
weaker subjects (S2 and S3) experienced the force-based control interfaces as
fatiguing suggests that sEMG-based control interfaces could be a better solution
for adults with DMD. Yet force-based control interfaces can be a better
alternative for those cases in which voluntary forces are higher than the
stiffness forces of the arms.
PMID- 28701170
TI - Antimicrobial susceptibility among Gram-positive and Gram-negative organisms
collected from the Latin American region between 2004 and 2015 as part of the
Tigecycline Evaluation and Surveillance Trial.
AB - BACKGROUND: The in vitro activity of tigecycline and comparator agents was
evaluated against Gram-positive and Gram-negative isolates collected in Latin
American centers between 2004 and 2015 as part of the Tigecycline Evaluation and
Surveillance Trial (T.E.S.T.) global surveillance study. METHODS: Minimum
inhibitory concentrations (MICs) were determined using the broth microdilution
methodology according to the Clinical and Laboratory Standards Institute (CLSI)
guidelines. Antimicrobial susceptibility was determined using CLSI breakpoints,
except for tigecycline for which the US Food and Drugs Administration breakpoints
were used. RESULTS: A total of 48.3% (2202/4563) of Staphylococcus aureus
isolates were methicillin-resistant S. aureus (MRSA). All MRSA isolates were
susceptible to linezolid and vancomycin, and 99.9% (2199/2202) were susceptible
to tigecycline. Among Streptococcus pneumoniae isolates, 13.8% (198/1436) were
penicillin-resistant; all were susceptible to linezolid and vancomycin, and 98.0%
(194/198) were susceptible to tigecycline. Susceptibility was >99.0% for
linezolid and tigecycline against Enterococcus faecium and Enterococcus faecalis
isolates. A total of 40.8% (235/576) E. faecium and 1.6% (33/2004) E. faecalis
isolates were vancomycin-resistant. Among the Enterobacteriaceae, 36.3%
(1465/4032) of Klebsiella pneumoniae isolates, 16.4% (67/409) of Klebsiella
oxytoca isolates and 25.4% (1246/4912) of Escherichia coli isolates were extended
spectrum beta-lactamase (ESBL) producers. Of the ESBL-producing K. pneumoniae and
E. coli isolates, susceptibility was highest to tigecycline [93.4% (1369/1465)
and 99.8% (1244/1246), respectively] and meropenem [86.9% (1103/1270) and 97.0%
(1070/1103), respectively]. A total of 26.7% (966/3613) of Pseudomonas aeruginosa
isolates were multidrug-resistant (MDR). Among all P. aeruginosa isolates,
susceptibility was highest to amikacin [72.8% (2632/3613)]. A total of 70.3%
(1654/2354) of Acinetobacter baumannii isolates were MDR, and susceptibility was
highest to minocycline [88.3% (2079/2354) for all isolates, 86.2% (1426/1654) for
MDR isolates]. Tigecycline had the lowest MIC90 (2 mg/L) among A. baumannii
isolates, including MDR isolates. CONCLUSIONS: This study of isolates from Latin
America shows that linezolid, vancomycin and tigecycline continue to be active in
vitro against important Gram-positive organisms such as MRSA, and that
susceptibility rates to meropenem and tigecycline against members of the
Enterobacteriaceae, including ESBL-producers, were high. However, we report that
Latin America has high rates of MRSA, MDR A. baumannii and ESBL-producing
Enterobacteriaceae which require continued monitoring.
PMID- 28701171
TI - Identification and characterization of single nucleotide polymorphism markers in
FADS2 gene associated with olive oil fatty acids composition.
AB - BACKGROUND: Genotyping of the FAD2.1 and FAD2.3 polymorphisms in the fatty acid
desaturase 2 gene (FADS2) shows that they are associated with the fatty acids
composition of olive oil samples. However, these associations require further
confirmation in the Tunisian olive oil cultivars, and little is known about the
effect of polymorphisms in fatty acid-related genes on olive oil mono- and poly-
unsaturated fatty acids distribution. METHODS: A set of olive oils from 12
Tunisian cultivars was chosen. The fatty acid composition of each olive oil
sample was determined by gas chromatography. Statistical and modeling Bayesian
analyses were used to assess whether the FAD2.1 and FAD2.3 genotypes were
associated with fatty acids composition. RESULTS: The TT-FAD2.1 and the GG-FAD2.3
genotypes were found to be associated with a lower proportion of oleic acid
(C18:1) (r = -0.778, p = 0.003; r = -0.781, p= 0.003) as well as higher
proportion of linoleic (C18:2) (r = 0.693, p = 0.012; r = -0.759, p= 0.004) and
palmitic acids (C16:0) (r = 0.643, p = 0.024; r = -0.503, p= 0.095), making
varieties with this haplotype (i.e. Chemlali Sfax and Meski) producing more
saturated (C16: 0) and polyunsaturated acids than oleic acid. The latter plays a
major role in preventing several diseases. CONCLUSION: The two associations FADS2
FAD2.1 and FADS2 FAD2.3 with the fatty acid compositions of olive oil samples
were identified among the studied olive cultivars. These associations differed
between studied cultivars, which might explain variability in lipidic composition
among them and consequently reflecting genetic diversity through differences in
gene expression and biochemical pathways. FADS2 locus would constitute thus a
good marker for detecting interesting lipidic chemotypes among commercial olive
oils.
PMID- 28701173
TI - 15-oxoeicosatetraenoic acid mediates monocyte adhesion to endothelial cell.
AB - BACKGROUND: A great number of studies reported that 12/15-lipoxygenase (12/15-LO)
played an important role in atherosclerosis. And its arachidonic acid(AA)
metabolite, 15(S)-hydroperoxy-5,8,11,13-(Z,Z,Z,E)-eicosatetraenoic acid (15(S)
HETE), is demonstrated to mediate endothelial dysfunction. 15-oxo-5,8,11,13
(Z,Z,Z,E)-eicosatetraenoic acid (15-oxo-ETE) was formed from 15
hydroxyprostaglandin dehydrogenase (PGDH)-mediated oxidation of 15(S)-HETE.
However, relatively little is known about the biological effects of 15-oxo-ETE in
cardiovascular disease. Here, we explore the likely role of 15-lipoxygenase (LO)
1-mediated AA metabolism,15-oxo-ETE, in the early pathogenesis of
atherosclerosis. METHODS: The 15-oxo-ETE level in serum was detected by means of
liquid chromatography and online tandem mass spectrometry (LC-MS/MS). And the
underlying mechanisms were illuminated by molecular techniques, including
immunoblotting, MTT assay, immunocytochemistry and Immunohistochemistry. RESULTS:
Increased 15-oxo-ETE level is found in in patients with acute myocardial
infarction (AMI). After 15-oxo-ETE treatment, Human umbilical vein endothelial
cells (HUVECs) showed more attractive to monocytes, whereas monocyte adhesion is
suppressed when treated with PKC inhibitor. In ex vivo study, exposure of
arteries from C57 mice and ApoE-/-mice to 15-oxo-ETE led to significantly
increased E-selectin expression and monocyte adhesion. CONCLUSIONS: This is the
first report that 15-oxo-ETE promotes early pathological process of
atherosclerosis by accelerating E-selectin expression and monocyte adhesion. 15
oxo-ETE -induced monocyte adhesion is partly attributable to activation of PKC.
PMID- 28701175
TI - Isolation and characterization of equine endometrial mesenchymal stromal cells.
AB - BACKGROUND: Equine mesenchymal stromal/stem cells (MSCs) are most commonly
harvested from bone marrow (BM) or adipose tissue, requiring the use of surgical
procedures. By contrast, the uterus can be accessed nonsurgically, and may
provide a more readily available cell source. While human endometrium is known to
harbor mesenchymal precursor cells, MSCs have not been identified in equine
endometrium. This study reports the isolation, culture, and characterization of
MSCs from equine endometrium. METHODS: The presence of MSC and pericyte markers
in endometrial sections was determined using immunohistochemistry. Stromal cells
were harvested and cultured after separation of epithelial cells from endometrial
fragments using Mucin-1-bound beads. For comparison, MSCs were also harvested
from BM. The expression of surface markers in endometrial and BM-derived MSCs was
characterized using flow cytometry and quantitative polymerase chain reaction.
MSCs were differentiated in vitro into adipogenic, chondrogenic, osteogenic, and
smooth muscle lineages. RESULTS: Typical markers of MSCs (CD29, CD44, CD90, and
CD105) and pericytes (NG2 and CD146) were localized in the equine endometrium.
Both endometrial and BM MSCs grew clonally and robustly expressed MSC and
pericyte markers in culture while showing greatly reduced or negligible
expression of hematopoietic markers (CD45, CD34) and MHC-II. Additionally, both
endometrial and BM MSCs differentiated into adipogenic, osteogenic, and
chondrogenic lineages in vitro, and endometrial MSCs had a distinct ability to
undergo smooth muscle differentiation. CONCLUSIONS: We have demonstrated for the
first time the presence of cells in equine endometrium that fulfill the
definition of MSCs. The equine endometrium may provide an alternative, easily
accessible source of MSCs, not only for therapeutic regeneration of the uterus,
but also for other tissues where MSCs from other sources are currently being used
therapeutically.
PMID- 28701174
TI - Normal milk microbiome is reestablished following experimental infection with
Escherichia coli independent of intramammary antibiotic treatment with a third
generation cephalosporin in bovines.
AB - BACKGROUND: The use of antimicrobials in food animals and the emergence of
antimicrobial resistance are global concerns. Ceftiofur is the only third
generation cephalosporin labeled for veterinary use in the USA, and it is the
drug of choice in the majority of dairy farms for the treatment of mastitis.
Here, we use next-generation sequencing to describe longitudinal changes that
occur in the milk microbiome before, during, and after infection and treatment
with ceftiofur. Twelve animals were intramammary challenged with Escherichia coli
in one quarter and randomly allocated to receive intramammary treatment with
ceftiofur (5d) or untreated controls. Serial samples were collected from -72 to
216 h relative to challenge from the challenged quarter, an ipsilateral quarter
assigned to the same treatment group, and from a third quarter that did not
undergo intervention. RESULTS: Infection with E. coli dramatically impacted
microbial diversity. Ceftiofur significantly decreased LogCFUs but had no
significant effect on the milk microbiome, rate of pathogen clearance, or somatic
cell count. At the end of the study, the microbial profile of infected quarters
was indistinguishable from pre-challenge samples in both treated and untreated
animals. Intramammary infusion with ceftiofur did not alter the healthy milk
(i.e., milk devoid of clots or serous appearance and collected from a mammary
gland that shows no clinical signs of mastitis) microbiome. CONCLUSIONS: Our
results indicate that the mammary gland harbors a resilient microbiome, capable
of reestablishing itself after experimental infection with E. coli independent of
antimicrobial treatment.
PMID- 28701176
TI - Angiostrongylus vasorum in Romania: an extensive survey in red foxes, Vulpes
vulpes.
AB - BACKGROUND: Angiostrongylus vasorum is the causative agent of canine
angiostrongylosis, a severe snail-borne disease of dogs. Red foxes are important
natural reservoirs of infection, and surveys of foxes provide a more objective
picture of the parasite distribution. Our aim was to investigate the possibility
of the presence of A. vasorum in red foxes from the western part of Romania and
to analyse the risk factors related to the sex, age and geographic origin of the
foxes. Between July 2016 and April 2017, 567 hunted red foxes from 10 counties of
western Romania were examined by necropsy for the presence of lungworms. RESULTS:
Overall, the infection with A. vasorum has been found in 24 red foxes (4.2%)
originating in four counties (Mures, Hunedoara, Salaj and Cluj). There was no
significant difference between the prevalence in males and females, between
juveniles and adults and between counties. CONCLUSIONS: This is the first report
of autochthonous infections of A. vasorum in Romania, showing a relatively low
prevalence and extending eastwards the known distributional range of this
parasite in Europe. The presence of autochthonous cases in domestic dogs in
Romania remains to be confirmed by further studies.
PMID- 28701177
TI - Longitudinal development of the gut microbiome and metabolome in preterm neonates
with late onset sepsis and healthy controls.
AB - BACKGROUND: Late onset sepsis (LOS) in preterm infants is associated with
considerable morbidity and mortality. While studies have implicated gut bacteria
in the aetiology of the disease, functional analysis and mechanistic insights are
generally lacking. We performed temporal bacterial (n = 613) and metabolomic (n =
63) profiling on extensively sampled stool from 7 infants with LOS and 28 matched
healthy (no LOS or NEC) controls. RESULTS: The bacteria isolated in diagnostic
blood culture usually corresponded to the dominant bacterial genera in the gut
microbiome. Longitudinal changes were monitored based on preterm gut community
types (PGCTs), where control infants had an increased number of PGCTs compared to
LOS infants (P = 0.011). PGCT 6, characterised by Bifidobacteria dominance, was
only present in control infants. Metabolite profiles differed between LOS and
control infants at diagnosis and 7 days later, but not 7 days prior to diagnosis.
Bifidobacteria was positively correlated with control metabolites, including
raffinose, sucrose, and acetic acid. CONCLUSIONS: Using multi-omic analysis, we
show that the gut microbiome is involved in the pathogenesis of LOS. While the
causative agent of LOS varies, it is usually abundant in the gut. Bifidobacteria
dominance was associated with control infants, and the presence of this organism
may directly protect, or act as a marker for protection, against gut epithelial
translocation. While the metabolomic data is preliminary, the findings support
that gut development and protection in preterm infants is associated with
increased in prebiotic oligosaccharides (e.g. raffinose) and the growth of
beneficial bacteria (e.g. Bifidobacterium).
PMID- 28701178
TI - The future of mechanical ventilation: lessons from the present and the past.
AB - The adverse effects of mechanical ventilation in acute respiratory distress
syndrome (ARDS) arise from two main causes: unphysiological increases of
transpulmonary pressure and unphysiological increases/decreases of pleural
pressure during positive or negative pressure ventilation. The transpulmonary
pressure-related side effects primarily account for ventilator-induced lung
injury (VILI) while the pleural pressure-related side effects primarily account
for hemodynamic alterations. The changes of transpulmonary pressure and pleural
pressure resulting from a given applied driving pressure depend on the relative
elastances of the lung and chest wall. The term 'volutrauma' should refer to
excessive strain, while 'barotrauma' should refer to excessive stress. Strains
exceeding 1.5, corresponding to a stress above ~20 cmH2O in humans, are severely
damaging in experimental animals. Apart from high tidal volumes and high
transpulmonary pressures, the respiratory rate and inspiratory flow may also play
roles in the genesis of VILI. We do not know which fraction of mortality is
attributable to VILI with ventilation comparable to that reported in recent
clinical practice surveys (tidal volume ~7.5 ml/kg, positive end-expiratory
pressure (PEEP) ~8 cmH2O, rate ~20 bpm, associated mortality ~35%). Therefore, a
more complete and individually personalized understanding of ARDS lung mechanics
and its interaction with the ventilator is needed to improve future care.
Knowledge of functional lung size would allow the quantitative estimation of
strain. The determination of lung inhomogeneity/stress raisers would help assess
local stresses; the measurement of lung recruitability would guide PEEP selection
to optimize lung size and homogeneity. Finding a safety threshold for mechanical
power, normalized to functional lung volume and tissue heterogeneity, may help
precisely define the safety limits of ventilating the individual in question.
When a mechanical ventilation set cannot be found to avoid an excessive risk of
VILI, alternative methods (such as the artificial lung) should be considered.
PMID- 28701179
TI - A study on relationship between elderly sarcopenia and inflammatory factors IL-6
and TNF-alpha.
AB - BACKGROUND: This report aims to study the relationship between sarcopenia of
elderly in community and inflammatory factors IL-6 and TNF-alpha. METHODS: A
total of 441 elders who undertook physical examinations were included into this
study. The age of these subjects were >60, in which 235 subjects were male and
206 subjects were female. According to the diagnostic standards of sarcopenia set
by EWGSOP and AWGS, these subjects were divided into two groups: sarcopenia, and
non-sarcopenia groups. The living habits, disease status, biochemical indexes,
and levels of IL-6 and TNF-alpha of these subjects were investigated. RESULTS:
The morbidity rate of sarcopenia was 17.02% in male subjects and 18.9% in female
subjects. In elderly subjects >80 years old, morbidity rate was 25.3% in male
subjects and 35.1% in female subjects. The history of smoking in patients with
sarcopenia was long, and their regular exercise history was short (P < 0.01).
Furthermore, differences in handgrip strength (HG), fat-free mass (FFM), bone
mineral content (BMC), plasma albumin (ALB) and serum creatinine (Cr), and body
fat content (FAT) in patients between the sarcopenia and non-sarcopenia groups
were statistically significant (P < 0.05). Moreover, differences in IL-6 and TNF
alpha levels between these two groups were statistically significant (P < 0.05).
In addition, BMI was positively correlated to TNF-alpha levels, and ALB was
negatively correlated to IL-6; while BMI and VFA were positively correlated to
TNF-alpha levels, and SMM, HDL-C, Hb, HG were negatively correlated to IL-6 level
(P < 0.05). Multiple linear regression analysis suggested plasma ALB and BMI were
the independent risk factors of TNF-alpha, while VFA was the independent risk
factor of IL-6. CONCLUSIONS: The onset of sarcopenia was associated with poor
exercise habits, disease history, and nutritional status. The emergence of
sarcopenia was accompanied by increased levels of inflammation factors TNF-alpha
and IL-6. Plasma albumin, BMI, and VFA were inflammatory factor predictors of TNF
and IL-6.
PMID- 28701180
TI - Influence of genetic variants on toxicity to anti-tubercular agents: a systematic
review and meta-analysis (protocol).
AB - BACKGROUND: Tuberculosis patients receiving anti-tuberculosis treatment may
experience serious adverse drug reactions, such as hepatotoxicity. Genetic risk
factors, such as polymorphisms of the NAT2, CYP2E1 and GSTM1 genes, may increase
the risk of experiencing such toxicity events. Many pharmacogenetic studies have
investigated the association between genetic variants and anti-tuberculosis drug
related toxicity events, and several meta-analyses have synthesised data from
these studies, although conclusions from these meta-analyses are conflicting.
Many meta-analyses also have serious methodological limitations, such as applying
restrictive inclusion criteria, or not assessing the quality of included studies.
Most also only consider hepatotoxicity outcomes and specific genetic variants.
The purpose of this systematic review and meta-analysis is to give a
comprehensive evaluation of the evidence base for associations between any
genetic variant and anti-tuberculosis drug-related toxicity. METHODS: We will
search for studies in MEDLINE, EMBASE, BIOSIS and Web of Science. We will also
hand search reference lists from relevant studies and contact experts in the
field. We will include cohort studies, case-control studies and randomised
controlled trials that recruited patients with tuberculosis who were either
already established on anti-tuberculosis treatment or were commencing treatment
and who were genotyped to investigate the effect of genetic variants on any anti
tuberculosis drug-related toxicity outcome. One author will screen abstracts to
identify potentially relevant studies and will then obtain the full text for each
potentially relevant study in order to assess eligibility. At each of these
stages, a second author will independently screen/assess 10% of studies. Two
authors will independently extract data and assess the quality of studies using a
pre-piloted data extraction form. If appropriate, we will pool estimates of
effect for each genotype on each outcome using meta-analyses stratified by
ethnicity. DISCUSSION: Our review and meta-analysis will update and add to the
existing research in this field. By not restricting the scope of the review to a
specific drug, genetic variant, or toxicity outcome, we hope to synthesise data
for associations between genetic variants and anti-tuberculosis drug-related
toxicity outcomes that have previously not been summarised in systematic reviews,
and consequently, add to the knowledge base of the pharmacogenetics of anti
tuberculosis drugs. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42017068448.
PMID- 28701181
TI - fastQ_brew: module for analysis, preprocessing, and reformatting of FASTQ
sequence data.
AB - BACKGROUND: Next generation sequencing datasets are stored as FASTQ formatted
files. In order to avoid downstream artefacts, it is critical to implement a
robust preprocessing protocol of the FASTQ sequence in order to determine the
integrity and quality of the data. RESULTS: Here I describe fastQ_brew which is a
package that provides a suite of methods to evaluate sequence data in FASTQ
format and efficiently implements a variety of manipulations to filter sequence
data by size, quality and/or sequence. fastQ_brew allows for mismatch searches to
adapter sequences, left and right end trimming, removal of duplicate reads, as
well as reads containing non-designated bases. fastQ_brew also returns summary
statistics on the unfiltered and filtered FASTQ data, and offers FASTQ to FASTA
conversion as well as FASTQ reverse complement and DNA to RNA manipulations.
CONCLUSIONS: fastQ_brew is open source and freely available to all users at the
following webpage: https://github.com/dohalloran/fastQ_brew .
PMID- 28701182
TI - Do we really need to differentiate mesenchymal stem cells into insulin-producing
cells for attenuation of the autoimmune responses in type 1 diabetes:
immunoprophylactic effects of precursors to insulin-producing cells.
AB - BACKGROUND: Type 1 diabetes (T1D) is a multifactorial autoimmune disorder where
pancreatic beta cells are lost before the clinical manifestations of the disease.
Administration of mesenchymal stem cells (MSCs) or MSCs differentiated into
insulin-producing cells (IPCs) have yielded limited success when used
therapeutically. We have evaluated the immunoprophylactic potentials of
precursors to insulin-producing cells (pIPCs) and IPCs in nonobese diabetic (NOD)
mice to ask a basic question: do we need to differentiate MSCs into IPCs or will
pIPCs suffice to attenuate autoimmune responses in T1D? METHODS: Bone marrow
derived MSCs from Balb/c mice were characterized following the International
Society for Cellular Therapy (ISCT) guidelines. MSCs cultured in high-glucose
media for 11 to 13 passages were characterized for the expression of pancreatic
lineage genes using real-time polymerase chain reaction. Expression of the PDX1
gene in pIPCs was assessed using Western blot and fluorescence-activated cell
sorting (FACS). Triple-positive MSCs were differentiated into IPCs using a three
step protocol after sorting them for cell surface markers, i.e. CD29, CD44, and
SCA-1. Nonobese diabetic mice were administered pIPCs, IPCs, or phosphate
buffered saline (PBS) into the tail vein at weeks 9 or 10 and followed-up for 29
30 weeks for fasting blood glucose levels. Two consecutive blood sugar levels of
more than 250 mg/dl were considered diabetic. RESULTS: MSCs grown in high-glucose
media for 11 to 13 passages expressed genes of the pancreatic lineage such as
PDX1, beta2, neurogenin, PAX4, Insulin, and glucagon. Furthermore, Western blot
and FACS analysis for PDX-1, a transcription factor necessary for beta cell
maturation, confirmed that these cells were precursors of insulin-producing cells
(pIPCs). NOD mice administered with pIPCs were better protected from developing
diabetes with a protective efficacy of 78.4% (p < 0.009); however, administration
of IPCs gave protective efficacy of 55% at the end of 28-30 weeks. CONCLUSIONS:
Precursors to insulin-producing cells seem to have better potential to arrest
autoimmune response in type 1 diabetes when administered before the onset of the
disease in NOD mice. When translated to humans, autologous mesenchymal stem cells
grown in high-glucose media for 10 to 13 passages may have beneficial effects in
individuals at high risk of developing type 1 diabetes.
PMID- 28701183
TI - Ruxolitinib found to cause eyelash growth: a case report.
AB - BACKGROUND: Hypereosinophilic syndrome is a hematologic disorder in which the
eosinophils proliferate. Oral Janus kinase inhibitors are known to be effective
treating hypereosinophilic syndrome. Janus kinase inhibitors have also
demonstrated efficacy in alopecia. Madarosis is a condition in which the
eyelashes are missing or absent and can been seen in alopecia patients. CASE
PRESENTATION: We present the case of a 77-year-old Asian man who was diagnosed
with hypereosinophilic syndrome, refractive to all medications except
ruxolitinib. He responded well. It was noted unexpectedly that his eyelashes grew
much longer than they were normally. CONCLUSIONS: Previous studies have
demonstrated an improvement in alopecia areata, with increased hair growth on the
head and eyebrows. This study demonstrates that longer eyelashes may be another
effect of oral Janus kinase inhibitors. We report the first case of eyelash
elongation and thickening in a patient taking ruxolitinib. Physicians and
patients should be aware of the side effect of these Janus kinase inhibitors.
Further investigation is needed to ascertain whether ruxolitinib or other
interleukin inhibitors can aid in the treatment of madarosis.
PMID- 28701184
TI - Developing a community-based psycho-social intervention with older people and
third sector workers for anxiety and depression: a qualitative study.
AB - BACKGROUND: One-in-five people in the UK experience anxiety and/or depression in
later life. However, anxiety and depression remain poorly detected in older
people, particularly in those with chronic physical ill health. In the UK, a
stepped care approach, to manage common mental health problems, is advocated
which includes service provision from non-statutory organisations (including
third/voluntary sector). However, evidence to support such provision, including
the most effective interventions, is limited. The qualitative study reported here
constitutes the first phase of a feasibility study which aims to assess whether
third sector workers can deliver a psychosocial intervention to older people with
anxiety and/or depression. The aim of this qualitative study is to explore the
views of older people and third sector workers about anxiety and depression among
older people in order to refine an intervention to be delivered by third sector
workers. METHODS: Semi-structured interviews with participants recruited through
purposive sampling from third sector groups in North Staffordshire. Interviews
were digitally recorded with consent, transcribed and analysed using principles
of constant comparison. RESULTS: Nineteen older people and 9 third sector workers
were interviewed. Key themes included: multiple forms of loss, mental health as a
personal burden to bear, having courage and providing/receiving encouragement,
self-worth and the value of group activities, and tensions in existing service
provision, including barriers and gaps. CONCLUSIONS: The experience of loss was
seen as central to feelings of anxiety and depression among community-dwelling
older people. This study contributes to the evidence pointing to the scale and
severity of mental health needs for some older people which can arise from
multiple forms of loss, and which present a significant challenge to health,
social care and third sector services. The findings informed development of a
psychosocial intervention and training for third sector workers to deliver the
intervention.
PMID- 28701185
TI - Case report: perioperative management of caesarean section for a parturient with
mitochondrial myopathy.
AB - BACKGROUND: Mitochondrial myopathies represent a group of disorders caused by
mitochondrial defects that disrupt energy production. Most patients have issues
from infancy to early childhood. Pregnancy in women with mitochondrial myopathy
is uncommon and the management for these parturients is full of challenges. CASE
PRESENTATION: A 36-year-old woman with mitochondrial myopathy was scheduled for
caesarean section under a combined spinal-epidural anaesthesia and multi-model
analgesia. The parturient was safe and the delivery was performed safely and
smoothly, but there were some complications after surgery due to the complex
condition of the patient. After consultation with and treatment from multiple
disciplines, both the parturient and neonate were well and discharged.
CONCLUSION: It is important that patients with mitochondrial diseases are
comprehensively assessed and monitored perioperatively.
PMID- 28701186
TI - The oral fungal mycobiome: characteristics and relation to periodontitis in a
pilot study.
AB - BACKGROUND: The oral fungal microbiome (mycobiome) is not well characterized,
particularly in relation to oral diseases such as periodontal disease. We aimed
to describe and compare the oral mycobiome of subjects with and without
periodontal disease. RESULTS: We characterized the oral mycobiome in 30 adult
subjects (15 with periodontal disease, 15 with good oral health) by sequencing
the taxonomically informative pan-fungal internal transcribed spacer (ITS) gene
in DNA extracted from oral wash samples. We observed at least 81 genera and 154
fungal species across all samples. Candida and Aspergillus were the most
frequently observed genera (isolated from 100% of participants), followed by
Penicillium (97%), Schizophyllum (93%), Rhodotorula (90%), and Gibberella (83%).
Candida and Aspergillus were also the most highly abundant genera in the samples
(median relative abundance = 21% and 44%, respectively). Aspergillus niger was
the most highly abundant species in the samples (median relative abundance =
44%). We did not observe significant differences in overall oral mycobiome
diversity or composition between participants with periodontal disease and
participants with good oral health, nor did we observe significant differences in
phylum through species level taxon relative abundance or carriage between the two
groups. Genus Candida, previously associated with periodontal disease in culture
based studies, had higher median relative abundance in participants with
periodontal disease (33.2%) compared to participants with oral health (2.2%),
though the difference was not significant (p = 0.52). Additionally, within the
periodontal disease group, median relative abundance of Candida increased with
increasing number of permanent teeth lost (1-2 teeth lost: 3.2%; 3-4 teeth lost:
16.6%; >=5 teeth lost: 73.9%; p = 0.11), though sample size was small for this
analysis. CONCLUSIONS: In this first study comprehensively characterizing the
oral mycobiome of adults with periodontal disease or good oral health, we
observed trends of higher Candida abundance in participants with periodontal
disease, and participants with greater tooth loss. Small sample size may have
limited the power to detect significant associations. Larger studies including
subgingival samples may further establish the core oral mycobiome in health, and
relate it to periodontal disease.
PMID- 28701187
TI - NucDiff: in-depth characterization and annotation of differences between two sets
of DNA sequences.
AB - BACKGROUND: Comparing sets of sequences is a situation frequently encountered in
bioinformatics, examples being comparing an assembly to a reference genome, or
two genomes to each other. The purpose of the comparison is usually to find where
the two sets differ, e.g. to find where a subsequence is repeated or deleted, or
where insertions have been introduced. Such comparisons can be done using whole
genome alignments. Several tools for making such alignments exist, but none of
them 1) provides detailed information about the types and locations of all
differences between the two sets of sequences, 2) enables visualisation of
alignment results at different levels of detail, and 3) carefully takes genomic
repeats into consideration. RESULTS: We here present NucDiff, a tool aimed at
locating and categorizing differences between two sets of closely related DNA
sequences. NucDiff is able to deal with very fragmented genomes, repeated
sequences, and various local differences and structural rearrangements. NucDiff
determines differences by a rigorous analysis of alignment results obtained by
the NUCmer, delta-filter and show-snps programs in the MUMmer sequence alignment
package. All differences found are categorized according to a carefully defined
classification scheme covering all possible differences between two sequences.
Information about the differences is made available as GFF3 files, thus enabling
visualisation using genome browsers as well as usage of the results as a
component in an analysis pipeline. NucDiff was tested with varying parameters for
the alignment step and compared with existing alternatives, called QUAST and
dnadiff. CONCLUSIONS: We have developed a whole genome alignment difference
classification scheme together with the program NucDiff for finding such
differences. The proposed classification scheme is comprehensive and can be used
by other tools. NucDiff performs comparably to QUAST and dnadiff but gives much
more detailed results that can easily be visualized. NucDiff is freely available
on https://github.com/uio-cels/NucDiff under the MPL license.
PMID- 28701189
TI - Stromal derived factor-1 mediates the lung regenerative effects of mesenchymal
stem cells in a rodent model of bronchopulmonary dysplasia.
AB - BACKGROUND: Mesenchymal stem cells (MSCs) attenuate lung injury in experimental
models of bronchopulmonary dysplasia (BPD). Stromal derived factor-1 (SDF-1), a
chemokine secreted by MSCs, modulates angiogenesis and stem cell recruitment.
Here we tested the hypothesis that SDF-1 mediates MSC protective effects in
experimental BPD by modulating angiogenesis. METHODS: SDF-1 was knocked down in
MSCs using lentiviral vectors carrying anti-SDF-1 short hairpin RNA (MSC-SDF KD).
Non-silencing short hairpin RNA was used as control (MSC-NS control). Newborn
rats exposed to normoxia or hyperoxia (FiO2 = 0.85) for 3 weeks, were randomly
assigned to receive a single intra-tracheal injection (IT) of MSC-NS control or
MSC-SDF KD (1 * 106 cells/50 MUl) or placebo on postnatal day 7. The degree of
alveolarization, lung angiogenesis, inflammation, and pulmonary hypertension (PH)
were assessed at postnatal day 21. RESULTS: Administration of IT MSC-NS control
improved lung alveolarization, angiogenesis and inflammation, and attenuated PH
in newborn rats with hyperoxia-induced lung injury (HILI). In contrast, knockdown
of SDF-1 in MSCs significantly reduced their beneficial effects on
alveolarization, angiogenesis, inflammation and PH. CONCLUSIONS: The therapeutic
benefits of MSCs in neonatal HILI are in part mediated by SDF-1, through anti
inflammatory and angiogenesis promoting mechanisms. Therapies directly targeting
this chemokine may provide a novel strategy for the treatment of BPD.
PMID- 28701188
TI - Tall height and obesity are associated with an increased risk of aggressive
prostate cancer: results from the EPIC cohort study.
AB - BACKGROUND: The relationship between body size and prostate cancer risk, and in
particular risk by tumour characteristics, is not clear because most studies have
not differentiated between high-grade or advanced stage tumours, but rather have
assessed risk with a combined category of aggressive disease. We investigated the
association of height and adiposity with incidence of and death from prostate
cancer in 141,896 men in the European Prospective Investigation into Cancer and
Nutrition (EPIC) cohort. METHODS: Multivariable-adjusted Cox proportional hazards
models were used to calculate hazard ratios (HRs) and 95% confidence intervals
(CIs). After an average of 13.9 years of follow-up, there were 7024 incident
prostate cancers and 934 prostate cancer deaths. RESULTS: Height was not
associated with total prostate cancer risk. Subgroup analyses showed
heterogeneity in the association with height by tumour grade (P heterogeneity =
0.002), with a positive association with risk for high-grade but not low
intermediate-grade disease (HR for high-grade disease tallest versus shortest
fifth of height, 1.54; 95% CI, 1.18-2.03). Greater height was also associated
with a higher risk for prostate cancer death (HR = 1.43, 1.14-1.80). Body mass
index (BMI) was significantly inversely associated with total prostate cancer,
but there was evidence of heterogeneity by tumour grade (P heterogeneity = 0.01;
HR = 0.89, 0.79-0.99 for low-intermediate grade and HR = 1.32, 1.01-1.72 for high
grade prostate cancer) and stage (P heterogeneity = 0.01; HR = 0.86, 0.75-0.99
for localised stage and HR = 1.11, 0.92-1.33 for advanced stage). BMI was
positively associated with prostate cancer death (HR = 1.35, 1.09-1.68). The
results for waist circumference were generally similar to those for BMI, but the
associations were slightly stronger for high-grade (HR = 1.43, 1.07-1.92) and
fatal prostate cancer (HR = 1.55, 1.23-1.96). CONCLUSIONS: The findings from this
large prospective study show that men who are taller and who have greater
adiposity have an elevated risk of high-grade prostate cancer and prostate cancer
death.
PMID- 28701190
TI - A novel algorithm for the treatment strategy for advanced epithelial ovarian
cancer: consecutive imaging, frailty assessment, and diagnostic laparoscopy.
AB - BACKGROUND: This study aimed to evaluate the perioperative outcomes and
prognostic impact of the consecutive steps of imaging, frailty assessment, and
diagnostic laparoscopy (DLS) in patients with advanced epithelial ovarian cancer
(EOC). METHODS: Patients diagnosed with EOC during 2012-2015 were analyzed
retrospectively. Surgical and survival outcomes were compared between three
treatment groups: patients without high tumor dissemination (HTD) who underwent
primary debulking surgery (PDS group); patients with HTD who underwent DLS (DLS
group); and patients with HTD diagnosed by cytological confirmation of malignancy
followed by neoadjuvant chemotherapy (NACT group). RESULTS: Of 181 patients, 85,
38, and 58 underwent PDS, DLS, and NACT, respectively. Among the 38 consecutive
patients who initially underwent DLS, 6 were considered suitable for PDS; the
remaining 32 were eligible for NACT followed by interval debulking surgery. The
median operative times of debulking surgery in the PDS, DLS, and NACT groups were
365 min (interquartile range [IQR]: 216.5-476.5 min), 266.2 min (IQR: 160.3-193.5
min), and 339.0 min (IQR: 205-425 min; P = 0.042), respectively, with respective
median estimated blood loss volumes of 962.2 mL (IQR: 300-1037.5 mL), 267.1 mL
(IQR: 150-450 mL), and 861.7 mL (IQR: 150-1200 mL; P = 0.023). The DLS group had
significantly reduced transfusion requirements and intensive care unit admission
rates (P = 0.006). The Kaplan-Meier survival analysis indicated significantly
poor PFS in the NACT group. However, there was no significant difference in OS
among the three groups. CONCLUSIONS: The consecutive steps of imaging, frailty
assessment, and DLS might facilitate rapid assessments of peritoneal disease
extent and resectability; this novel algorithm might also be used to
individualize treatment.
PMID- 28701192
TI - Protection of farm goats by combinations of recombinant peptides and formalin
inactivated spores from a lethal Bacillus anthracis challenge under field
conditions.
AB - BACKGROUND: Bacillus (B.) anthracis, the causal agent of anthrax, is effectively
controlled by the Sterne live spore vaccine (34F2) in animals. However, live
spore vaccines are not suitable for simultaneous vaccination and antibiotic
treatment of animals being at risk of infection in an outbreak situation. Non
living vaccines could close this gap. RESULTS: In this study a combination of
recombinant protective antigen and recombinant Bacillus collagen-like antigen
(rBclA) with or without formalin inactivated spores (FIS), targeted at raising an
immune response against both the toxins and the spore of B. anthracis, was tested
for immunogenicity and protectiveness in goats. Two groups of goats received from
local farmers of the Kars region of Turkey were immunized thrice in three weeks
intervals and challenged together with non-vaccinated controls with virulent B.
anthracis, four weeks after last immunization. In spite of low or none measurable
toxin neutralizing antibodies and a surprisingly low immune response to the
rBclA, 80% of the goats receiving the complete vaccine were protected against a
lethal challenge. Moreover, the course of antibody responses indicates that a two
step vaccination schedule could be sufficient for protection. CONCLUSION: The
combination of recombinant protein antigens and FIS induces a protective immune
response in goats. The non-living nature of this vaccine would allow for a
concomitant antibiotic treatment and vaccination procedure. Further studies
should clarify how this vaccine candidate performs in a post infection scenario
controlled by antibiotics.
PMID- 28701191
TI - Blood-brain barrier and foetal-onset hydrocephalus, with a view on potential
novel treatments beyond managing CSF flow.
AB - Despite decades of research, no compelling non-surgical therapies have been
developed for foetal hydrocephalus. So far, most efforts have pointed to
repairing disturbances in the cerebrospinal fluid (CSF) flow and to avoid further
brain damage. There are no reports trying to prevent or diminish abnormalities in
brain development which are inseparably associated with hydrocephalus. A key
problem in the treatment of hydrocephalus is the blood-brain barrier that
restricts the access to the brain for therapeutic compounds or systemically
grafted cells. Recent investigations have started to open an avenue for the
development of a cell therapy for foetal-onset hydrocephalus. Potential cells to
be used for brain grafting include: (1) pluripotential neural stem cells; (2)
mesenchymal stem cells; (3) genetically-engineered stem cells; (4) choroid plexus
cells and (5) subcommissural organ cells. Expected outcomes are a proper
microenvironment for the embryonic neurogenic niche and, consequent normal brain
development.
PMID- 28701193
TI - Do elections matter for private-sector healthcare management in Brazil? An
analysis of municipal health policy.
AB - BACKGROUND: This study analyzed several political determinants of increased
private-sector management in Brazilian health care. In Brazil, the poor depend
almost exclusively on the public Unified Health System (the SUS), which remains
severely underfunded. Given the overhead costs associated with privately
contracted health services, increased private management is one driver of higher
expenditures in the system. Although left parties campaign most vocally in
support of greater public control of the SUS, the extent to which their stated
positions translate into health care policy remains untested. METHODS: Drawing on
multiple publicly available data sources, we used linear regression to analyze
how political party-in-power and existing private sector health care contracting
affect the share of privately managed health care services and outsourcing in
municipalities. Data from two election periods-2004 to 2008 and 2008 to 2012-were
analyzed. RESULTS: Our findings showed that although private sector contracting
varies greatly across municipalities, this variation is not systematically
associated with political party in power. This suggests that electoral politics
plays a relatively minor role in municipal-level health care administration.
Existing levels of private sector management appear to have a greater effect on
the public-private makeup of the Brazilian healthcare system, suggesting a strong
role of path dependence in the evolution of Brazilian health care delivery.
CONCLUSION: Despite campaign rhetoric asserting distinct positions on
privatization in the SUS, factors other than political party in power have a
greater effect on private-sector health system management at the municipal-level
in Brazil. Given the limited effect of elections on this issue, strengthening
participatory bodies such as municipal health councils may better enfranchise
citizens in the fundamental debate over public and private roles in the health
care sector.
PMID- 28701194
TI - Characterization and productivity profiles of Aedes aegypti (L.) breeding
habitats across rural and urban landscapes in western and coastal Kenya.
AB - BACKGROUND: Aedes aegypti, the principal vector for dengue and other emerging
arboviruses, breeds preferentially in various man-made and natural container
habitats. In the absence of vaccine, epidemiological surveillance and vector
control remain the best practices for preventing dengue outbreaks. Effective
vector control depends on a good understanding of larval and adult vector ecology
of which little is known in Kenya. In the current study, we sought to
characterize breeding habitats and establish container productivity profiles of
Ae. aegypti in rural and urban sites in western and coastal Kenya. METHODS:
Twenty sentinel houses in each of four study sites (in western and coastal Kenya)
were assessed for immature mosquito infestation once a month for a period of 24
months (June 2014 to May 2016). All water-holding containers in and around the
households were inspected for Ae. aegypti larvae and pupae. RESULTS: Collections
were made from a total of 22,144 container visits: Chulaimbo (7575) and Kisumu
(8003) in the west, and from Msambweni (3199) and Ukunda (3367) on the coast. Of
these, only 4-5.6% were positive for Ae. aegypti immatures. In all four sites,
significantly more positive containers were located outdoors than indoors. A
total of 17,537 Ae. aegypti immatures were sampled from 10 container types. The
most important habitat types were buckets, drums, tires, and pots, which produced
over 75% of all the pupae. Key outdoor containers in the coast were buckets,
drums and tires, which accounted for 82% of the pupae, while pots and tires were
the only key containers in the western region producing 70% of the pupae. Drums,
buckets and pots were the key indoor containers, producing nearly all of the
pupae in the coastal sites. No pupae were collected indoors in the western
region. The coastal region produced significantly more Ae. aegypti immatures than
the western region both inside and outside the sentinel houses. CONCLUSIONS:
These results indicate that productive Ae. aegypti larval habitats are abundant
outdoors and that only a few containers produce a majority of the pupae. Although
the numbers were lower, productive habitats were detected within households.
Targeting source reduction efforts towards these productive containers both
inside and outside homes is likely to be a cost-effective way to reduce arboviral
transmission in these regions.
PMID- 28701195
TI - A meta-analysis of temporal changes of response in the placebo arm of surgical
randomized controlled trials: an update.
AB - BACKGROUND: Temporal changes in the placebo arm of randomized controlled trials
(RCTs) have not been thoroughly investigated, despite the fact that results of
RCTs depend on the comparison between arms. METHODS: In this update of our
earlier systematic review and meta-analysis, we set out to investigate the effect
of assessment time and number of visits on the magnitude of change from baseline
in the placebo arm of these trials. We used linear mixed-effects models to
account for within-trial correlations. RESULTS: Across all 47 trials the
magnitude of response in the placebo arm did not change with time (beta =
0.0070, 95% CI -0.024, 0.010) or visit (beta = -0.033, 95% CI -0.082, 0.017) and
remained significantly different from baseline for at least 12 months or seven
follow-up visits. Change in the placebo arm in trials with subjective outcomes
was large (beta0 = 0.68, 95% CI 0.53, 0.82) and relatively constant across time
(beta = -0.0042, 95% CI -0.024, 0.016) and visit (beta = -0.029, 95% CI -0.089,
0.031), whereas in trials with objective outcomes the response was smaller (beta0
= 0.28, 95% CI 0.11, 0.46) and diminished with time (beta = -0.030, 95% CI
0.050, -0.010), but not with visit (beta = -0.099, 95% CI -0.30, 0.11). For
trials with assessed outcomes, there was no significant effect of time (beta =
0.0071, 95% CI -0.026, 0.011) or visit (beta = -0.032, 95% CI -0.33, 0.26);
however, these results should be interpreted with caution due to the small number
of studies, and high clinical heterogeneity between studies. In trials with pain
as an outcome, the improvement was significant (beta0 = 0.91, 95% CI 0.75, 1.07),
but there was no effect of time (beta = -0.013, 95% CI -0.06, 0.03) or visit
(beta = -0.045, 95% CI -0.16, 0.069), and pain ratings remained significantly
different from baseline for 12 months or seven visits. CONCLUSIONS: These results
are consistent with our previous findings. In trials with subjective outcomes
response in the placebo arm remains large and relatively constant for at least a
year, which is interesting considering that this is an effect of a single
application of an invasive procedure. The lack of effect of time and visit number
on subjective outcomes raises further questions regarding whether the observed
response is the result of placebo effect or the result of bias.
PMID- 28701196
TI - Functional beliefs and risk minimizing beliefs among Thai healthcare workers in
Maharaj Nakorn Chiang Mai hospital: its association with intention to quit
tobacco and alcohol.
AB - BACKGROUND: Individual health beliefs are likely to play a key role in how people
respond to knowledge and information about the potential harm from smoking and
alcohol abuse. The objectives of the study were to 1) explore whether functional
beliefs and risk minimizing beliefs were associated with intention to quit
smoking and confidence to quit smoking and 2) explore whether functional beliefs
and risk minimizing beliefs were associated with intention to quit alcohol
drinking and confidence to quit alcohol drinking. METHODS: A cross-sectional
survey was conducted in 2013 among health care workers working in Thailand. Using
predicted factor scores from factor analysis, the relationship between factor
scores for each of the two beliefs and intention to quit and confidence to quit
were tested using ANOVA and further adjusted for age and sex using linear
regression. RESULTS: Functional beliefs were inversely associated with the
intention to quit and confidence to quit smoking. Both functional beliefs and
risk minimizing beliefs were each inversely associated with the intention to quit
and confidence to quit alcohol drinking. CONCLUSION: Our study enhances the
understanding of the complexities of health beliefs regarding these two commonly
abused substances. As functional beliefs were associated with smoking and alcohol
use, interventions to counter the cultural values and individual beliefs about
the benefits of smoking and alcohol use are needed. Tackling risk minimizing
beliefs by providing individualized feedback regarding harm may also be useful in
alcohol drinkers.
PMID- 28701197
TI - A case of bowel perforation due to traumatic hernia at a pelvic fracture site: a
case report and review of the literature.
AB - BACKGROUND: Common complications of pelvic fractures include visceral injury,
large-volume hemorrhage, genitourinary injury, rectal injury, and pulmonary
embolism. On the other hand, traumatic hernia is a rare complication, especially
in association with pelvic fractures. We report a case of bowel perforation due
to traumatic hernia at a pelvic fracture site. CASE PRESENTATION: A 65-year-old
female was presented at our hospital for further examination and treatment of
ileus. She was diagnosed with bowel perforation due to traumatic hernia at a
pelvic fracture site, and an emergency operation was thus immediately performed.
We performed segmental jejunum resection and constructed jejunostomy, and the
iliac bone fracture was fixed with four pins. In the postoperative course, she
received antibiotics and vasopressors for septic shock. However, there was no
need for either a ventilator, dialysis or admission to the ICU. At seven days
after the operation, a residual abscess was detected in the pouch of Douglas. We
performed percutaneous drainage (Clavien-Dindo IIIa) and jejunostomy closedown 35
days after the first operation. The postoperative course was without
complication, but she received rehabilitation until she was able to walk unaided.
She was discharged 64 days after the first operation. CONCLUSION: The occurrence
of traumatic hernia is rare, especially in association with pelvic fractures.
Although its rarity, traumatic hernia follows a severe course. Thus, proper
diagnosis and effective treatment are necessary. Surgeons treating patients with
pelvic injuries should consider the possibility of any complications and perform
a work-up examination in order to achieve an accurate diagnosis at an earlier
time point.
PMID- 28701199
TI - Effectiveness of distance learning strategies for continuing professional
development (CPD) for rural allied health practitioners: a systematic review.
AB - BACKGROUND: Allied health professionals working in rural areas face unique
challenges, often with limited access to resources. Accessing continuing
professional development is one of those challenges and is related to retention
of workforce. Effectiveness of distance learning strategies for continuing
professional development in rural allied healthcare workers has not been
evaluated. METHODS: We searched 17 databases and the grey literature up to
September 2016 following the PRISMA guidelines. Any primary studies were included
that focussed on allied health and distance delivery regardless of education
topic or study design. Two independent reviewers extracted data and critically
appraised the selected studies. RESULTS: The search returned 5257 results. With
removal of duplicate references, we reviewed 3964 article titles and abstracts; n
= 206 appeared potentially eligible and were scrutinised via full text screening;
n = 14 were included. Studies were published between 1997 and 2016, were of
varied methodological quality and were predominantly from Australia, USA and
Canada with a focus on satisfaction of learners with the delivery method or on
measures of educational outcomes. Technologies used to deliver distance education
included video conference, teleconference, web based platforms and virtual
reality. Early papers tended to focus more on the technology characteristics than
educational outcomes. Some studies compared technology based delivery to face to
face modes and found satisfaction and learning outcomes to be on par. Only three
studies reported on practice change following the educational intervention and,
despite a suggestion there is a link between the constructs, none measured the
relationship between access to continuing professional development and workforce
retention. CONCLUSION: Technology based options of delivery have a high utility,
however the complex inter-relatedness of time, use, travel, location, costs,
interactivity, learning outcomes and educational design suggest a need for more
sophisticated consideration by educational providers. TRIAL REGISTRATION:
Registration with PROSPERO 30 June 2016: CRD42016041588 .
PMID- 28701198
TI - Scaffolding of long read assemblies using long range contact information.
AB - BACKGROUND: Long read technologies have revolutionized de novo genome assembly by
generating contigs orders of magnitude longer than that of short read assemblies.
Although assembly contiguity has increased, it usually does not reconstruct a
full chromosome or an arm of the chromosome, resulting in an unfinished
chromosome level assembly. To increase the contiguity of the assembly to the
chromosome level, different strategies are used which exploit long range contact
information between chromosomes in the genome. METHODS: We develop a scalable and
computationally efficient scaffolding method that can boost the assembly
contiguity to a large extent using genome-wide chromatin interaction data such as
Hi-C. RESULTS: we demonstrate an algorithm that uses Hi-C data for longer-range
scaffolding of de novo long read genome assemblies. We tested our methods on the
human and goat genome assemblies. We compare our scaffolds with the scaffolds
generated by LACHESIS based on various metrics. CONCLUSION: Our new algorithm
SALSA produces more accurate scaffolds compared to the existing state of the art
method LACHESIS.
PMID- 28701200
TI - Assessing colonoscopic inspection skill using a virtual withdrawal simulation: a
preliminary validation of performance metrics.
AB - BACKGROUND: The effectiveness of colonoscopy for diagnosing and preventing colon
cancer is largely dependent on the ability of endoscopists to fully inspect the
colonic mucosa, which they achieve primarily through skilled manipulation of the
colonoscope during withdrawal. Performance assessment during live procedures is
problematic. However, a virtual withdrawal simulation can help identify and
parameterise actions linked to successful inspection, and offer standardised
assessments for trainees. METHODS: Eleven experienced endoscopists and 18
endoscopy novices (medical students) completed a mucosal inspection task during
three simulated colonoscopic withdrawals. The two groups were compared on 10
performance metrics to preliminarily assess the validity of these measures to
describe inspection quality. Four metrics were related to aspects of polyp
detection: percentage of polyp markers found; number of polyp markers found per
minute; percentage of the mucosal surface illuminated by the colonoscope (>=0.5
s); and percentage of polyp markers illuminated (>=2.5 s) but not identified. A
further six metrics described the movement of the colonoscope: withdrawal time;
linear distance travelled by the colonoscope tip; total distance travelled by the
colonoscope tip; and distance travelled by the colonoscope tip due to movement of
the up/down angulation control, movement of the left/right angulation control,
and axial shaft rotation. RESULTS: Statistically significant experienced-novice
differences were found for 8 of the 10 performance metrics (p's < .005). Compared
with novices, experienced endoscopists inspected more of the mucosa and detected
more polyp markers, at a faster rate. Despite completing the withdrawals more
quickly than the novices, the experienced endoscopists also moved the colonoscope
more in terms of linear distance travelled and overall tip movement, with greater
use of both the up/down angulation control and axial shaft rotation. However, the
groups did not differ in the number of polyp markers visible on the monitor but
not identified, or movement of the left/right angulation control. All metrics
that yielded significant group differences had adequate to excellent internal
consistency reliability (alpha = .79 to .90). CONCLUSIONS: These systematic
differences confirm the potential of the simulated withdrawal task for evaluating
inspection skills and strategies. It may be useful for training, and assessment
of trainee competence.
PMID- 28701201
TI - Erratum to: determinants of vitamin D status in young adults: influence of
lifestyle, sociodemographic and anthropometric factors.
PMID- 28701202
TI - Erratum to: gender-specific linkages of parents' childhood physical abuse and
neglect with children's problem behaviour: evidence from Japan.
PMID- 28701203
TI - Discovery of a novel dominant mutation in the REN gene after forty years of renal
disease: a case report.
AB - BACKGROUND: Heterozygous mutations in the gene encoding renin (REN) cause
autosomal dominant tubulointerstitial kidney disease (ADTKD), early-onset anaemia
and hyperuricaemia; only four different mutations have been described in the
published literature to date. We report a novel dominant REN mutation discovered
in an individual after forty years of renal disease. CASE PRESENTATION: A 57 year
old Caucasian woman with chronic kidney disease stage five was reviewed in a
regional joint renal genetics clinic. She had initially been diagnosed with
chronic pyelonephritis in adolescence, around the same time that she was
investigated for anaemia out of keeping with her degree of renal impairment.
Hyperuricaemia was identified in her twenties following an episode of gout. A
diagnosis of ADTKD was not made until the age of 37 years, when her mother was
also found to have kidney disease and commenced haemodialysis. The patient's
renal function continued to slowly deteriorate and, twenty years later, her
sister was worked up as a potential donor for kidney transplantation. Revisiting
the maternal family history during the transplant work up prompted a referral to
clinical genetics and urgent REN genetic testing was requested for the patient,
leading to discovery of a heterozygous mutation in the REN gene: c.49 T > C,
p.(Trp17Arg). This variant was not identified in her otherwise healthy sister,
allowing pre-emptive live renal transplantation to take place shortly afterwards.
CONCLUSIONS: In an era where genetic testing is becoming much more readily
available, this case highlights the importance of considering a genetic aetiology
in all patients with long-standing renal disease and a relevant family history.
Establishing a genetic diagnosis of ADTKD-REN in this individual with chronic
anaemia, hyperuricaemia and slowly progressive renal impairment helped to
identify a suitable live kidney donor and allowed successful pre-emptive
transplantation to take place.
PMID- 28701204
TI - Criteria and models for the distribution of casualties in trauma-related mass
casualty incidents: a systematic literature review protocol.
AB - BACKGROUND: One of the most critical practices in mass casualty incident
management is vacating the victims from scene of the incident and transporting
them to proper healthcare facilities. Decision on distribution of casualties
needs to be taken on pre-developed policies and structured decision support
mechanisms. While many studies tried to present models for the distribution of
casualties, no systematic review has yet been conducted to evaluate the existing
models on casualty distribution following mass casualty incidents. A systematic
review is therefore needed to examine the existing models of patient distribution
and to provide a summary of the models. This systematic review protocol is aimed
to examine the existing models and extracting rules and principles of mass
casualty distribution. METHODS: This study will comprehensively investigate
existing papers with search phrases and terms including "mass casualty incident",
distribution, evacuation, and Mesh terms directly corresponding to search
phrases. No limitations on the type of studies, date of publication, or language
of the relevant documents will be imposed. PubMed, Web of Science, Scopus, and
Google Scholar will be searched to access the relevant documents. Included papers
will be critically appraised by two independent reviewers. The data including
incidents type, scene characteristics, patient features, pre-hospital resources,
and hospital resources will be categorized. Subgroup analysis will be conducted
when possible. DISCUSSION: To the best of our knowledge, no study has yet
addressed the effects and interaction of contributing factors on the decision
making processes for casualty's distribution. This is the first study that
comprehensively assesses and critically appraises the current models of casualty
distribution. This study will provide evidences about models and criteria for
casualty distribution following mass casualty incidents. SYSTEMATIC REVIEW
REGISTRATION: PROSPERO Registration Number: CRD42016049115.
PMID- 28701205
TI - Art therapy and music reminiscence activity in the prevention of cognitive
decline: study protocol for a randomized controlled trial.
AB - BACKGROUND: Attention has shifted to the use of non-pharmacological interventions
to prevent cognitive decline as a preventive strategy, as well as for those at
risk and those with mild cognitive impairment. Early introduction of psycho
social interventions can address cognitive decline and significantly impact
quality of life and the wellbeing of elderly individuals. This pilot study
explores the feasibility of using art therapy and music reminiscence activity to
improve the cognition of community living elderly with mild cognitive impairment.
METHODS/DESIGN: This open-label, interventional study involves a parallel
randomized controlled trial design with three arms (two intervention arms and a
control group) over a nine-month period. Participants will be community-living
elderly individuals aged 60-85 years, both genders, who meet predefined inclusion
and exclusion criteria. In the initial three months, interventions will be
provided weekly and for the remaining six months fortnightly. A sample size of 90
participants is targeted based on expected neuropsychological test performance, a
primary outcome measure, and drop-out rates. The randomization procedure will be
carried out via a web-based randomization system. Interventions will be provided
by trained staff with a control group not receiving any intervention but
continuing life as usual. Assessments will be done at baseline, three months, and
nine months, and include neuroimaging to measure cerebral changes and
neuropsychological tests to measure for changes in cognition. Secondary outcome
measures will include mood changes in anxiety and depression and telomere
lengths. Statistical analysis will be undertaken by statisticians; all efficacy
analysis will be carried out on an intention-to-treat basis. Primary and
secondary outcomes will be modeled using the linear mixed model for repeated
measurements and further analysis may be undertaken to adjust for potential
confounders. DISCUSSION: This will be the first study to compare the
effectiveness of art therapy and music reminiscence activity in a randomized
controlled trial. We expect that the trial will provide useful evidence for
developing psychosocial interventions for the elderly with mild cognitive
impairment. TRIAL REGISTRATION: The study was registered on 7 July 2016 at
Clinical Trials.gov, a service of the US National Institute of Health (
NCT02854085 ), retrospectively.
PMID- 28701206
TI - Physical activity level in people with age related white matter changes
correlates to better motor performance, lower comorbidity and higher cognitive
level.
AB - BACKGROUND: Physical activity plays a pivotal role in the development of
disability and may modify the negative effect of vascular risk factors on
progression of both cardio and cerebrovascular disorders. The aim of this study
was to evaluate the activity level in people with age-related white matter
changes as identified on magnetic resonance imaging (MRI) in relation to motor
performance, cognition and perceived health. METHODS: Data came from the first
year follow up of one participating centers of the LADIS study. Fifty one
subjects were first enrolled in the study. Complete first year follow up data was
available for 41 subjects. Information on comorbidity, physical activity level,
physical function, cognition, level of white matter changes and perceived health
was collected. Physical activity level was classified with a yes or no question
and with the Frenchay Activities Index (FAI). RESULTS: Only 36% of the subjects
in this study were physically active according to the yes/no question. 27.5% of
the subjects were active according to the FAI score which evaluates the everyday
activities. Being active discriminated subjects with better physical function.
Subjects active according to the FAI score had a higher cognitive level (p <=
0.01), lower comorbidity (p = 0.02) and performed better on all motor function
tasks as assessed by walking speed (p <= 0.01) and the Short Physical Performance
battery (SPPB) (p <= 0.01). CONCLUSIONS: Being physically active seems to be a
long term protective factor. In our study, the majority of subjects with Age
Related White Mattter Changes (ARWMC) with no or mild Instrumental Activity of
Daily Living (IADL) disability did not attain recommended level of activity at
first year follow up. Whether or not increasing physical activity may slow down
cognitive decline and lessen development of disability in physically inactive
subjects with manifest ARWC remains to be studied. TRIAL REGISTRATION: not
applicable.
PMID- 28701207
TI - Development of a core outcome set for clinical trials in squamous cell carcinoma:
study protocol for a systematic review of the literature and identification of a
core outcome set using a Delphi survey.
AB - BACKGROUND: Squamous cell carcinoma (SCC) is a common skin cancer that poses a
risk of metastasis. Clinical investigations into SCC treatment are common, but
the outcomes reported are highly variable, omitted, or clinically irrelevant. The
outcome heterogeneity and reporting bias of these studies leave clinicians unable
to accurately compare studies. Core outcome sets (COSs) are an agreed minimum set
of outcomes recommended to be measured and reported in all clinical trials of a
given condition or disease. Although COSs are under development for several
dermatologic conditions, work has yet to be done to identify core outcomes
specific for SCC. METHODS/DESIGN: Outcome extraction for COS generation will
occur via four methods: (1) systematic literature review; (2) patient interviews;
(3) other published sources; and (4) input from stakeholders in medicine,
pharmacy, and other relevant industries. The list of outcomes will be revaluated
by the Measuring PRiority Outcome Variables via Excellence in Dermatologic
surgery (IMPROVED) Steering Committee. Delphi processes will be performed
separately by expert clinicians and patients to condense the list of outcomes
generated. A consensus meeting with relevant stakeholders will be conducted after
the Delphi exercise to further select outcomes, taking into account participant
scores. At the end of the meeting, members will vote and decide on a final
recommended set of core outcomes. The Core Outcome Measures in Effectiveness
Trials (COMET) organization and the Cochrane Skin Group - Core Outcome Set
Initiative (CSG-COUSIN) will serve as advisers throughout the COS generation
process. DISCUSSION: Comparison of clinical trials via systematic reviews and
meta-analyses is facilitated when investigators study outcomes that are relevant
and similar. The aim of this project is to develop a COS to guide use for future
clinical trials.
PMID- 28701208
TI - Expanding co-payment for methadone maintenance services in Vietnam: the
importance of addressing health and socioeconomic inequalities.
AB - BACKGROUND: Ensuring high enrollment while mobilizing resources through co
payment services is critical to the success of the methadone maintenance
treatment (MMT) program in Vietnam. This study assessed the willingness of
patients to pay (WTP) for different MMT services delivery models and determined
its associated factors. METHODS: A facility based survey was conducted among 1016
MMT patients (98.7% male, 42% aged 35 or less, and 67% living with spouse) in
five MMT clinics in Hanoi and Nam Dinh province in 2013. Socioeconomic, HIV and
health status, history of drug use and rehabilitation, and MMT experience were
interviewed. WTP was assessed using contingent valuation method, including a set
of double-bounded binary questions and a follow-up open-ended question. Point and
interval data models were used to estimate maximum willingness to pay. RESULTS:
95.5% patients were willing to pay for MMT at the monthly mean price of US$ 32
(95%CI = 28-35). Higher WTP was associated with higher level of educational
attainment, higher income, male sex, and had high expenses on opiates prior to
MMT. Patients who reported having any problem in Pain/ Discomfort, and who did
not have outpatient care last year were willing to pay less for MMT than others.
CONCLUSION: High level of WTP supports the co-payment policies as a strategy to
mobilize resources for the MMT program in Vietnam. However, it is necessary to
ensure equalities across patient groups by acknowledging socioeconomic status of
different settings and providing financial supports for disadvantaged patients
with severe health status.
PMID- 28701209
TI - Alantolactone, a natural sesquiterpene lactone, has potent antitumor activity
against glioblastoma by targeting IKKbeta kinase activity and interrupting NF
kappaB/COX-2-mediated signaling cascades.
AB - BACKGROUND: Glioblastoma multiforme (GBM) is one of the most refractory and
palindromic central nervous system (CNS) neoplasms, and current treatments have
poor effects in GBM patients. Hence, the identification of novel therapeutic
targets and the development of effective treatment strategies are essential.
Alantolactone (ATL) has a wide range of pharmacological activities, and its anti
tumor effect is receiving increasing attention. However, the molecular mechanism
underlying the anti-GBM activity of ATL remains poorly understood. METHODS: The
biological functions of ATL in GBM cells were investigated using
migration/invasion, colony formation and cell cycle/apoptosis assays. The
localization of nuclear factor kappa B (NF-kappaB) p50/p65 and its binding to the
cyclooxygenase 2 (COX-2) promoter were determined using confocal
immunofluorescence, a streptavidin-agarose pulldown assay and a chromatin
immunoprecipitation (ChIP) assay. IKKbeta kinase activity was determined using a
cell IKKbeta kinase activity spectrophotometry quantitative detection kit and a
molecular docking study. LC-MS/MS analysis was performed to determine the ability
of ATL to traverse the blood-brain barrier (BBB). The in vivo anti-tumor efficacy
of ATL was also analyzed in xenografted nude mice. Western blot analysis was
performed to detect the protein expression levels. RESULTS: ATL significantly
suppressed the growth of GBM in vivo and in vitro. ATL significantly reduced the
expression of COX-2 by inhibiting the kinase activity of IKKbeta by targeting the
ATP-binding site and then attenuating the binding of NF-kappaB to the COX-2
promoter region. Furthermore, ATL induced apoptosis by activating the cytochrome
c (cyt c)/caspase cascade signaling pathway. Moreover, ATL could penetrate the
BBB. CONCLUSIONS: ATL exerts its anti-tumor effects in human GBM cells at least
in part via NF-kappaB/COX-2-mediated signaling cascades by inhibiting IKKbeta
kinase activity. ATL, which is a natural small molecule inhibitor, is a promising
candidate for clinical applications in the treatment of CNS tumors.
PMID- 28701210
TI - Follicular Fluid redox involvement for ovarian follicle growth.
AB - As the human ovarian follicle enlarges in the course of a regular cycle or
following controlled ovarian stimulation, the changes in its structure reveal the
oocyte environment composed of cumulus oophorus cells and the follicular fluid
(FF).In contrast to the dynamic nature of cells, the fluid compartment appears as
a reservoir rich in biomolecules. In some aspects, it is similar to the plasma,
but it also exhibits differences that likely relate to its specific localization
around the oocyte. The chemical composition indicates that the follicular fluid
is able to detect and buffer excessive amounts of reactive oxygen species,
employing a variety of antioxidants, some of them components of the intracellular
milieu.An important part is played by albumin through specific cysteine residues.
But the fluid contains other molecules whose cysteine residues may be involved in
sensing and buffering the local oxidative conditions. How these molecules are
recruited and regulated to intervene such process is unknown but it is a critical
issue in reproduction.In fact, important proteins in the FF, that regulate
follicle growth and oocyte quality, exhibit cysteine residues at specific points,
whose untoward oxidation would result in functional loss. Therefore, preservation
of controlled oxidative conditions in the FF is a requirement for the fine-tuned
oocyte maturation process. In contrast, its disturbance enhances the
susceptibility to the establishment of reproductive disorders that would require
the intervention of reproductive medicine technology.
PMID- 28701211
TI - Inpatient rehabilitation for adult patients with Marfan syndrome: an
observational pilot study.
AB - BACKGROUND: Advances in medical, interventional and surgical treatment have
increased average life expectancy of patients with congenital heart defects. As a
result a new group of adult patients with congenital cardiac defects requires
medical rehabilitation. Patients with Marfan syndrome (MFS) are a relevant group
among these patients. So far, no reports on the effectiveness of specialized
rehabilitation programmes for MFS patients exist. We implemented an inpatient 3
week rehabilitation program for MFS patients at the Muehlenberg-Clinic for
rehabilitation and assessed the medical safety as well as the impact of the
program on physical fitness and psychological wellbeing of participants by means
of an observational pilot study. The comprehensive multidisciplinary program
included medical, physiotherapeutic, psychological and social issues. Two groups
including 8 and 10 individuals with verified MFS attended the programme.
Medically adverse events that occurred during the rehabilitation were registered.
Adverse events were defined as: any new cardiac arrhythmias such as atrial
fibrillation, ventricular tachycardia, cardiac syncope or any complications
located at the aorta. Psychological assessment was performed using Short Form-36
(SF-36), hospital anxiety and depression scale and other psychometric
questionnaires. Medical examinations included assessment of maximum power in
bicycle ergometry. All assessments were performed at the beginning and at the end
of the rehabilitation. Psychometric assessments were repeated 1 year after the
end of the programme for both groups, respectively. RESULTS: Patients were highly
satisfied with the programme and improved in almost all psychological and
physical fitness assessments. The pre-post-comparison resulted in significant
positive changes for mental health (p < .001 for SF-36 Mental Health), fatigue (p
< .05 for Fatigue Severity Scale), nociception (p < .05 for SF-36 Pain) and
vitality (p < .05 for SF-36 Vitality). Physical fitness improved from admission
to discharge (p < .001 for maximum power in bicycle ergometry, p < .05 for
maximum nordic walking distance). Considerable improvements persisted through 1
year follow-up. Medical assessments excluded medical problems or adverse events
caused by participation in the programme. CONCLUSIONS: In our study, inpatient
rehabilitation was both safe and helpful for MFS patients. They benefited in
terms of physical fitness, health related quality of life and in terms of
psychological wellbeing. An evaluation of the efficacy of the programme in a
controlled design as well as further conceptual improvements of our current
program is desirable.
PMID- 28701212
TI - Is the oocyte quality affected by endometriosis? A review of the literature.
AB - Endometriosis is an estrogen-dependent chronic inflammatory condition that
affects women in their reproductive period causing infertility and pelvic pain.
The disease, especially at the ovarian site has been shown to have a detrimental
impact on ovarian physiology. Indeed, sonographic and histologic data tend to
support the idea that ovarian follicles of endometriosis patients are decreased
in number and more atretic. Moreover, the local intrafollicular environment of
patients affected is characterized by alterations of the granulosa cell
compartment including reduced P450 aromatase expression and increased
intracellular reactive oxygen species generation. However, no comprehensive
evaluation of the literature addressing the effect of endometriosis on oocyte
quality from both a clinical and a biological perspective has so far been
conducted. Based on this systematic review of the literature, oocytes retrieved
from women affected by endometriosis are more likely to fail in vitro maturation
and to show altered morphology and lower cytoplasmic mitochondrial content
compared to women with other causes of infertility. Results from meta-analyses
addressing IVF outcomes in women affected would indicate that a reduction in the
number of mature oocytes retrieved is associated with endometriosis while a
reduction in fertilization rates is more likely to be associated with
minimal/mild rather than with moderate/severe disease. However, evidence in this
field is still far to be conclusive, especially with regards to the effects of
different stages of the disease and to the impact of patients' previous
medical/surgical treatment(s).
PMID- 28701213
TI - Survey of interdigital phlegmon outbreaks and their risk factors in free stall
dairy herds in Finland.
AB - BACKGROUND: Severe outbreaks of interdigital phlegmon (IP) associated with a high
morbidity and major economic losses have occurred in Finland in the past decade.
A survey was performed to indicate the current occurrence of infectious hoof
diseases and to identify herd level risk factors predisposing to an outbreak of
IP. RESULTS: Responses to a questionnaire revealed that an outbreak of IP defined
as morbidity >=5% within the 1st month of the outbreak, had occurred in 18.0% of
the respondent study farms. Risk factors for an outbreak included animal
transport between herds, i.e. either animal purchase or contract heifer rearing,
enlargement or renovation of the barn, and if the fields of the farm had been
organically cultivated. Having any kind of mechanical ventilation in comparison
to natural ventilation seemed to lower the risk of IP. Additionally, the farms
that had experienced an outbreak of IP often had other infectious hoof diseases.
However, it was unclear which disease appeared first. CONCLUSIONS: More attention
is needed before and during enlargement or renovation of the barn and substantial
planning is crucial for every part of the enlargement process in dairy farms.
PMID- 28701214
TI - The effect of oral acetazolamide on cystoid macular edema in hydroxychloroquine
retinopathy: a case report.
AB - BACKGROUND: Hydroxychloroquine (HCQ) retinopathy can accompany other retinal
complications such as cystoid macular edema (CME), which leads to central visual
loss. We report a case of CME with HCQ retinopathy that improved with the use of
oral acetazolamide, and discussed the possible mechanisms of CME in HCQ
retinopathy using multimodal imaging modalities. CASE PRESENTATION: A 62-year-old
patient with systemic lupus erythematosus (SLE) and HCQ retinopathy developed
bilateral CME with visual decline. Fluorescein angiography (FA) showed
fluorescein leakage in the macular and midperipheral area. After treatment with
oral acetazolamide (250 mg/day) for one month, CME was completely resolved, best
corrected visual acuity (BCVA) improved from 20/50 to 20/25, and FA examination
showed decreased dye leakage in the macular and midperipheral areas. CONCLUSIONS:
In cases of vision loss in HCQ retinopathy, it is important to consider not only
progression of maculopathy, but also development of CME, which can be effectively
treated with oral acetazolamide.
PMID- 28701215
TI - Continuous sweep versus discrete step protocols for studying effects of wearable
robot assistance magnitude.
AB - BACKGROUND: Different groups developed wearable robots for walking assistance,
but there is still a need for methods to quickly tune actuation parameters for
each robot and population or sometimes even for individual users. Protocols where
parameters are held constant for multiple minutes have traditionally been used
for evaluating responses to parameter changes such as metabolic rate or walking
symmetry. However, these discrete protocols are time-consuming. Recently,
protocols have been proposed where a parameter is changed in a continuous way.
The aim of the present study was to compare effects of continuously varying
assistance magnitude with a soft exosuit against discrete step conditions.
METHODS: Seven participants walked on a treadmill wearing a soft exosuit that
assists plantarflexion and hip flexion. In Continuous-up, peak exosuit ankle
moment linearly increased from approximately 0 to 38% of biological moment over
10 min. Continuous-down was the opposite. In Discrete, participants underwent
five periods of 5 min with steady peak moment levels distributed over the same
range as Continuous-up and Continuous-down. We calculated metabolic rate for the
entire Continuous-up and Continuous-down conditions and the last 2 min of each
Discrete force level. We compared kinematics, kinetics and metabolic rate between
conditions by curve fitting versus peak moment. RESULTS: Reduction in metabolic
rate compared to Powered-off was smaller in Continuous-up than in Continuous-down
at most peak moment levels, due to physiological dynamics causing metabolic
measurements in Continuous-up and Continuous-down to lag behind the values
expected during steady-state testing. When evaluating the average slope of
metabolic reduction over the entire peak moment range there was no significant
difference between Continuous-down and Discrete. Attempting to correct the lag in
metabolics by taking the average of Continuous-up and Continuous-down removed all
significant differences versus Discrete. For kinematic and kinetic parameters,
there were no differences between all conditions. CONCLUSIONS: The finding that
there were no differences in biomechanical parameters between all conditions
suggests that biomechanical parameters can be recorded with the shortest protocol
condition (i.e. single Continuous directions). The shorter time and higher
resolution data of continuous sweep protocols hold promise for the future study
of human interaction with wearable robots.
PMID- 28701216
TI - The effect of ambient temperature on type-2-diabetes: case-crossover analysis of
4+ million GP consultations across England.
AB - BACKGROUND: Given the double jeopardy of global increases in rates of obesity and
climate change, it is increasingly important to recognise the dangers posed to
diabetic patients during periods of extreme weather. We aimed to characterise the
associations between ambient temperature and general medical practitioner
consultations made by a cohort of type-2 diabetic patients. Evidence on the
effects of temperature variation in the primary care setting is currently
limited. METHODS: Case-crossover analysis of 4,474,943 consultations in England
during 2012-2014, linked to localised temperature at place of residence for each
patient. Conditional logistic regression was used to assess associations between
each temperature-related consultation and control days matched on day-of-week.
RESULTS: There was an increased odds of seeking medical consultation associated
with high temperatures: Odds ratio (OR) = 1.097 (95% confidence interval = 1.041,
1.156) per 1 degrees C increase above 22 degrees C. Odds during low
temperatures below 0 degrees C were also significantly raised: OR = 1.024
(1.019, 1.030). Heat-related consultations were particularly high among diabetics
with cardiovascular comorbidities: OR = 1.171 (1.031, 1.331), but there was no
heightened risk with renal failure or neuropathy comorbidities. Surprisingly,
lower odds of heat-related consultation were associated with the use of
diuretics, anticholinergics, antipsychotics or antidepressants compared to non
use, especially among those with cardiovascular comorbidities, although
differences were not statistically significant. CONCLUSIONS: Type-2 diabetic
patients are at increased odds of medical consultation during days of temperature
extremes, especially during hot weather. The common assumption that certain
medication use heightens the risk of heat illness was not borne-out by our study
on diabetics in a primary care setting and such advice may need to be
reconsidered in heat protection plans.
PMID- 28701217
TI - Association of baseline steroid use with long-term rates of infection and sepsis
in the REGARDS cohort.
AB - BACKGROUND: Prior studies associate steroid use with infection risk but were
limited to select populations and short follow-up periods. The association of
steroid use with long-term risk of community-acquired infections is unknown. We
sought to determine the association of steroid risk with long-term risks of
community- acquired infections and sepsis. METHODS: We used data on 30,239 adults
aged >= 45 years old from the Reasons for Geographic and Racial Differences in
Stroke (REGARDS) cohort. The primary exposure was oral or injectable steroid use,
determined from medication inventory obtained at baseline in-home visit. The
primary outcome was time to first infection event during 2003-2012, determined
through adjudicated review of hospital records. We determined associations
between baseline steroid use and first infection hospitalization events using Cox
proportional hazards models, adjusting for demographics, health behaviors,
chronic medical conditions, and medication adherence. Among the first infection
hospitalization events, we also determined the association between baseline
steroid use and sepsis. RESULTS: Steroid use was reported in 2.24% (n = 677) of
the study population. There were 2593 incident infection events during the 10
year follow-up period. Infection incidence rates were higher for steroid than non
steroid users (37.99 vs. 13.79 per 1000 person-years). Steroid use was
independently associated with increased risk of infection (adjusted HR 2.10, 95%
CI: 1.73-2.56). Among first-infection events, steroid use was associated with
increased odds of sepsis (adjusted OR 2.11, 95% CI: 1.33-3.36). The associations
persisted in propensity matched analyses as well as models stratified by
propensity score and medication adherence. CONCLUSIONS: In this population-based
cohort study, baseline steroid use was associated with increased long-term risks
of community-acquired infections and sepsis.
PMID- 28701218
TI - Investigating reproducibility and tracking provenance - A genomic workflow case
study.
AB - BACKGROUND: Computational bioinformatics workflows are extensively used to
analyse genomics data, with different approaches available to support
implementation and execution of these workflows. Reproducibility is one of the
core principles for any scientific workflow and remains a challenge, which is not
fully addressed. This is due to incomplete understanding of reproducibility
requirements and assumptions of workflow definition approaches. Provenance
information should be tracked and used to capture all these requirements
supporting reusability of existing workflows. RESULTS: We have implemented a
complex but widely deployed bioinformatics workflow using three representative
approaches to workflow definition and execution. Through implementation, we
identified assumptions implicit in these approaches that ultimately produce
insufficient documentation of workflow requirements resulting in failed execution
of the workflow. This study proposes a set of recommendations that aims to
mitigate these assumptions and guides the scientific community to accomplish
reproducible science, hence addressing reproducibility crisis. CONCLUSIONS:
Reproducing, adapting or even repeating a bioinformatics workflow in any
environment requires substantial technical knowledge of the workflow execution
environment, resolving analysis assumptions and rigorous compliance with
reproducibility requirements. Towards these goals, we propose conclusive
recommendations that along with an explicit declaration of workflow specification
would result in enhanced reproducibility of computational genomic analyses.
PMID- 28701219
TI - Excellent local control and tolerance profile after stereotactic body
radiotherapy of advanced hepatocellular carcinoma.
AB - BACKGROUND: To evaluate the efficacy and toxicity of stereotactic body
radiotherapy (SBRT) in the treatment of advanced hepatocellular carcinoma (HCC).
MATERIAL AND METHODS: Patients with large HCCs (median diameter 7 cm, IQR 5-10
cm) with a Child-Turcotte-Pugh (CTP) score A (60%) or B (40%) and Barcelona
Clinic Liver Cancer (BCLC) classification stage B or C were treated with 3 to 12
fractions to allow personalized treatment according to the size of the lesions
and the proximity of the lesions to the organs at risk aiming to give high
biologically equivalent doses assuming an alpha/beta ratio of 10 Gy for HCC.
Primary end points were in-field local control and toxicity assessment. RESULTS:
Forty seven patients with 64 lesions were treated with SBRT (median 45 Gy in 3-12
fractions) with a median follow up for patients alive of 19 months. The median
biological effective dose was 76 Gy (IQR 62-86 Gy). Tumor vascular thrombosis was
present in 28% and an underlying liver disease in 87% (hepatitis B or C in 21%,
alcohol related in 51%, nonalcoholic steatohepatitis in 13% of the patients,
primary biliary cirrhosis 2%). Eighty three percent received prior and in most
cases multiple therapies. Local control at 1 year was 77%. The median overall
survival from the start of SBRT was 9 months (95% CI 7.7-10.3). Gastrointestinal
toxicities grade >= 2 were observed in 3 (6.4%) patients. An increase in CTP
score without disease progression was observed in 5 patients, of whom one patient
developed a radiation induced liver disease. One patient died due to liver
failure 4 months after treatment. CONCLUSION: SBRT is an effective local ablative
therapy which leads to high local control rates with moderate toxicity for
selected patients with large tumors.
PMID- 28701220
TI - Identification of QTL with large effect on seed weight in a selective population
of soybean with genome-wide association and fixation index analyses.
AB - BACKGROUND: Soybean seed weight is not only a yield component, but also a
critical trait for various soybean food products such as sprouts, edamame, soy
nuts, natto and miso. Linkage analysis and genome-wide association study (GWAS)
are two complementary and powerful tools to connect phenotypic differences to the
underlying contributing loci. Linkage analysis is based on progeny derived from
two parents, given sufficient sample size and biological replication, it usually
has high statistical power to map alleles with relatively small effect on
phenotype, however, linkage analysis of the bi-parental population can't detect
quantitative trait loci (QTL) that are fixed in the two parents. Because of the
small seed weight difference between the two parents in most families of previous
studies, these populations are not suitable to detect QTL that have considerable
effects on seed weight. GWAS is based on unrelated individuals to detect alleles
associated with the trait under investigation. The ability of GWAS to capture
major seed weight QTL depends on the frequency of the accessions with small and
large seed weight in the population being investigated. Our objective was to
identify QTL that had a pronounced effect on seed weight using a selective
population of soybean germplasm accessions and the approach of GWAS and fixation
index analysis. RESULTS: We selected 166 accessions from the USDA Soybean
Germplasm Collection with either large or small seed weight and could typically
grow in the same location. The accessions were evaluated for seed weight in the
field for two years and genotyped with the SoySNP50K BeadChip containing >42,000
SNPs. Of the 17 SNPs on six chromosomes that were significantly associated with
seed weight in two years based on a GWAS of the selective population, eight on
chromosome 4 or chromosome 17 had significant Fst values between the large and
small seed weight sub-populations. The seed weight difference of the two alleles
of these eight significant SNPs varied from 8.1 g to 11.7 g/100 seeds in two
years. We also identified haplotypes in three haplotype blocks with significant
effects on seed weight. These findings were validated in a panel with 3753
accessions from the USDA Soybean Germplasm Collection. CONCLUSION: This study
highlighted the usefulness of selective genotyping populations coupled with GWAS
and fixation index analysis for the identification of QTL with substantial
effects on seed weight in soybean. This approach may help geneticists and
breeders to more efficiently identify major QTL controlling other traits. The
major regions and haplotypes we have identified that control seed weight
differences in soybean will facilitate the identification of genes regulating
this important trait.
PMID- 28701221
TI - Helminth infections and practice of prevention and control measures among
pregnant women attending antenatal care at Anbesame health center, Northwest
Ethiopia.
AB - BACKGROUND: Helminth infections have a terrible impact on child growth and
development, and harm pregnant women. Regular treatment and long term preventive
interventions are important measures to break the transmission routes. Hence,
identifying the status of helminth infection and practices of prevention and
control measures among pregnant women is important in different geographical
areas of Ethiopia including our setting. METHODS: A cross-sectional study was
conducted on 180 pregnant women from March to June, 2015. About 2 g of stool was
collected and examined to identify helminth infections. Proportions and risk
factors of helminth infections were calculated using SPSS version 20. RESULTS:
Among the total 180 study participants, 38 (21.1% [95% CI 15.2-27.0%]) pregnant
women had helminth infections. Hookworm and Schistosoma mansoni were the only
identified helminth species. Thirty-six (20.0% [95% CI 14.3-25.7%]) and 4 (2.2%
[95% CI 0.2-4.2%]) pregnant women had hookworm and S. mansoni infections,
respectively. Of which, double infection (hookworm and S. mansoni) was found in
two pregnant women. Only 32 (17.8%) pregnant women had proper hand wash practice
after toilet, 48 (26.7%) drank treated water, and 40 (22.2%) wore shoes
regularly. Those pregnant women who did not take albendazole or mebendazole
dewormers (AOR 3.57; 95% CI 1.19-10.69; P 0.023) were more infected from helminth
infections. CONCLUSIONS: This study showed that there was a high intestinal
helminth infection among pregnant women, and low practice of prevention and
control measures. Thus, prevention and control measures should be strengthened in
the setting.
PMID- 28701222
TI - How well do ICD-9 physician claim diagnostic codes identify confirmed pertussis
cases in Alberta, Canada? A Canadian Immunization Research Network (CIRN) Study.
AB - BACKGROUND: Rates of Bordetella pertussis have been increasing in Alberta, Canada
despite vaccination programs. Waning immunity from existing acellular component
vaccines may be contributing to this. Vaccine effectiveness can be estimated
using a variety of data sources including diagnostic codes from physician billing
claims, public health records, reportable disease and laboratory databases. We
sought to determine if diagnostic codes from billing claims (administrative data)
are adequately sensitive and specific to identify pertussis cases among patients
who had undergone disease-specific laboratory testing. METHODS: Data were
extracted for 2004-2014 from a public health communicable disease database that
contained data on patients under investigation for B. pertussis (both those who
had laboratory tests and those who were epidemiologically linked to laboratory
confirmed cases) in Alberta, Canada. These were deterministically linked using a
unique lifetime person identifier to the provincial billing claims database,
which contains International Classification of Disease version 9 (ICD-9)
diagnostic codes for physician visits. We examined visits within 90 days of
laboratory testing. ICD-9 codes 033 (whooping cough), 033.0 (Bordetella
pertussis), 033.1 (B. parapertussis), 033.8 (whooping cough, other specified
organism), and 033.9 (whooping cough, other unspecified organism) in any of the
three diagnostic fields for a claim were classified as being pertussis-specific
codes. We calculated sensitivity, specificity, positive (PPV) and negative (NPV)
predictive values. RESULTS: We identified 22,883 unique patients under
investigation for B. pertussis. Of these, 22,095 underwent laboratory testing.
Among those who had a laboratory test, 2360 tested positive for pertussis. The
sensitivity of a pertussis-specific ICD-9 code for identifying a laboratory
confirmed case was 38.6%, specificity was 76.9%, PPV was 16.0%, and NPV was
91.6%. CONCLUSION: ICD-9 codes from physician billing claims data have low
sensitivity and moderate specificity to identify laboratory-confirmed pertussis
among persons tested for pertussis.
PMID- 28701224
TI - The 150 most important questions in cancer research and clinical oncology series:
questions 40-49.
AB - Since the beginning of 2017, Chinese Journal of Cancer has published a series of
important questions in cancer research and clinical oncology, which sparkle
diverse thoughts, interesting communications, and potential collaborations among
researchers all over the world. In this article, 10 more questions are presented
as followed. Question 40. Why do mice being used as tumorigenesis models raised
in different places or different conditions possess different tumor formation
rate? Question 41. How could we generate more effective anti-metastasis drugs?
Question 42. What is the molecular mechanism underlying heterogeneity of cancer
cachexia in patients with the same pathologic type? Question 43. Will patients
with oligo-metastatic disease be curable by immunotherapy plus stereotactic body
radiotherapy? Question 44. Can the Warburg effect regulation be targeted for
cancer treatment? Question 45. Why do adenocarcinomas seldom occur in the small
intestine? Question 46. Is Epstein-Barr virus infection a causal factor for nasal
natural killer/T cell lymphoma formation? Question 47. Why will not all but very
few human papillomavirus-infected patients eventually develop cervical cancer?
Question 48. Why do cervical carcinomas induced by human papilloma virus have a
low mutation rate in tumor suppressor genes? Question 49. Can viral infection
trigger lung cancer relapse?
PMID- 28701223
TI - Low-dose immunoglobulin G is not associated with mortality in patients with
sepsis and septic shock.
AB - BACKGROUND: The administration of low-dose intravenous immunoglobulin G (IVIgG)
(5 g/day for 3 days; approximate total 0.3 g/kg) is widely used as an adjunctive
treatment for patients with sepsis in Japan, but its efficacy in the reduction of
mortality has not been evaluated. We investigated whether the administration of
low-dose IVIgG is associated with clinically important outcomes including
intensive care unit (ICU) and in-hospital mortality. METHODS: This is a post-hoc
subgroup analysis of data from a retrospective cohort study, the Japan Septic
Disseminated Intravascular Coagulation (JSEPTIC DIC) study. The JSEPTIC DIC study
was conducted in 42 ICUs in 40 institutions throughout Japan, and it investigated
associations between sepsis-related coagulopathy, anticoagulation therapies, and
clinical outcomes of 3195 adult patients with sepsis and septic shock admitted to
ICUs from January 2011 through December 2013. To investigate associations between
low-dose IVIgG administration and mortalities, propensity score-based matching
analysis was used. RESULTS: IVIgG was administered to 960 patients (30.8%).
Patients who received IVIgG were more severely ill than those who did not (Acute
Physiology and Chronic Health Evaluation (APACHE) II score 24.2 +/- 8.8 vs 22.6
+/- 8.7, p < 0.001). They had higher ICU mortality (22.8% vs 17.4%, p < 0.001),
but similar in-hospital mortality (34.4% vs 31.0%, p = 0.066). In propensity
score-matched analysis, 653 pairs were created. Both ICU mortality and in
hospital mortality were similar between the two groups (21.0% vs 18.1%, p =
0.185, and 32.9% vs 28.6%, p = 0.093, respectively) using generalized estimating
equations fitted with logistic regression models adjusted for other therapeutic
interventions. The administration of IVIgG was not associated with ICU or in
hospital mortality (odds ratio (OR) 0.883; 95% confidence interval (CI) 0.655
1.192, p = 0.417, and OR 0.957, 95% CI, 0.724-1.265, p = 0.758, respectively).
CONCLUSIONS: In this analysis of a large cohort of patients with sepsis and
septic shock, the administration of low-dose IVIgG as an adjunctive therapy was
not associated with a decrease in ICU or in-hospital mortality. TRIAL
REGISTRATION: University Hospital Medical Information Network Individual Clinical
Trials Registry, UMIN-CTR000012543 . Registered on 10 December 2013.
PMID- 28701225
TI - Association of schizophrenia onset age and white matter integrity with treatment
effect of D-cycloserine: a randomized placebo-controlled double-blind crossover
study.
AB - BACKGROUND: It has been reported that drugs which promote the N-Methyl-D
aspartate-type glutamate receptor function by stimulating the glycine modulatory
site in the receptor improve negative symptoms and cognitive dysfunction in
schizophrenia patients being treated with antipsychotic drugs. METHODS: We
performed a placebo-controlled double-blind crossover study involving 41
schizophrenia patients in which D-cycloserine 50 mg/day was added-on, and the
influence of the onset age and association with white matter integrity on MR
diffusion tensor imaging were investigated for the first time. The patients were
evaluated using the Positive and Negative Syndrome Scale (PANSS), Scale for the
Assessment of Negative Symptoms (SANS), Brief Assessment of Cognition in
Schizophrenia (BACS), and other scales. RESULTS: D-cycloserine did not improve
positive or negative symptoms or cognitive dysfunction in schizophrenia. The
investigation in consideration of the onset age suggests that D-cycloserine may
aggravate negative symptoms of early-onset schizophrenia. The better treatment
effect of D-cycloserine on BACS was observed when the white matter integrity of
the sagittal stratum/ cingulum/fornix stria terminalis/genu of corpus
callosum/external capsule was higher, and the better treatment effect on PANSS
general psychopathology (PANSS-G) was observed when the white matter integrity of
the splenium of corpus callosum was higher. In contrast, the better treatment
effect of D-cycloserine on PANSS-G and SANS-IV were observed when the white
matter integrity of the posterior thalamic radiation (left) was lower.
CONCLUSION: It was suggested that response to D-cycloserine is influenced by the
onset age and white matter integrity. TRIAL REGISTRATION: UMIN Clinical Trials
Registry (number UMIN000000468 ). Registered 18 August 2006.
PMID- 28701226
TI - The application of geographic information systems (GIS) in identifying the
priority areas for maternal care and services.
AB - BACKGROUND: Improving maternal health is globally introduced as an important
health priority. The purpose of this study is to identify the high priority areas
which require more maternal health services in Kerman, Iran. METHODS: This is a
descriptive cross-sectional study, performed in 2015. The literatures were first
explored in order to extract geographic indicators and sub indicators relevant to
the maternal health. Data were collected by the use of a questionnaire designed
on the basis of AHP (Analytic Hierarchy Process) method. The validity and
reliability of the questionnaire were confirmed by three medical informatics
experts and test-retest method, respectively. Data were analyzed by Expert Choice
software in order to specify the weight and importance of each indicator. The
information were then added to Geographic Information System (GIS) to analyze and
create the related maps. RESULTS: Women's access to hospitals plays an important
role in identifying high priority areas which need maternal care and services.
More than half of the mothers in Kerman have a moderate level of access to
maternal care services. There is an association between facilities that are
provided for pregnant women and the existence of healthcare centers. Moreover,
there is a negative correlation between maternal death and the number of
facilities provided for medical care and services for pregnant women.
CONCLUSIONS: The application of GIS provides us with the capability to identify
high priority areas which need maternal care. According to current population
policies in Iran and the probable increase in the fertility rate, it is wise to
plan proper schedules to improve health care services for pregnant women in
Kerman.
PMID- 28701227
TI - High-flow nasal cannula oxygen therapy is superior to conventional oxygen therapy
but not to noninvasive mechanical ventilation on intubation rate: a systematic
review and meta-analysis.
AB - BACKGROUND: High-flow nasal cannula oxygen (HFNC) is a relatively new therapy
used in adults with respiratory failure. Whether it is superior to conventional
oxygen therapy (COT) or to noninvasive mechanical ventilation (NIV) remains
unclear. The aim of the present study was to investigate whether HFNC was
superior to either COT or NIV in adult acute respiratory failure patients.
METHODS: A review of the literature was conducted from the electronic databases
from inception up to 20 October 2016. Only randomized clinical trials comparing
HFNC with COT or HFNC with NIV were included. The intubation rate was the primary
outcome; secondary outcomes included the mechanical ventilation rate, the rate of
escalation of respiratory support and mortality. RESULTS: Eleven studies that
enrolled 3459 patients (HFNC, n = 1681) were included. There were eight studies
comparing HFNC with COT, two comparing HFNC with NIV, and one comparing all
three. HFNC was associated with a significant reduction in intubation rate (OR
0.52, 95% CI 0.34 to 0.79, P = 0.002), mechanical ventilation rate (OR 0.56, 95%
CI 0.33 to 0.97, P = 0.04) and the rate of escalation of respiratory support (OR
0.45, 95% CI 0.31 to 0.67, P < 0.0001) when compared to COT. There was no
difference in mortality between HFNC and COT utilization (OR 1.01, 95% CI 0.67 to
1.53, P = 0.96). When HFNC was compared to NIV, there was no difference in the
intubation rate (OR 0.96; 95% CI 0.66 to 1.39, P = 0.84), the rate of escalation
of respiratory support (OR 1.00, 95% CI 0.77 to 1.28, P = 0.97) or mortality (OR
0.85, 95% CI 0.43 to 1.68, P = 0.65). CONCLUSIONS: Compared to COT, HFNC reduced
the rate of intubation, mechanical ventilation and the escalation of respiratory
support. When compared to NIV, HFNC showed no better outcomes. Large-scale
randomized controlled trials are necessary to prove our findings. TRIAL
REGISTRATION: PROSPERO International prospective register of systematic reviews
on May 25, 2016 registration no. CRD42016039581 .
PMID- 28701229
TI - Anti-high mobility group box-1 (HMGB1) antibody attenuates kidney damage
following experimental crush injury and the possible role of the tumor necrosis
factor-alpha and c-Jun N-terminal kinase pathway.
AB - BACKGROUND: Inflammation plays a crucial role in kidney damage after crush
syndrome (CS). Several researchers report that high mobility group box-1 protein
(HMGB1) may be the vital trigger in kidney damage, and tumor necrosis factor
alpha (TNF-alpha) and c-Jun N-terminal kinase (JNK) are involve in this
pathophysiological process, but their biological roles are unclear. This study
aimed to explore the relationship between HMGB1, JNK, and TNF-alpha in kidney
damage. METHODS: The crush injury model was established using weight compression.
The reliability of the crush injury model was determined by hematoxylin-eosin
(HE) staining. Western blot was used to detect the expression of HMGB1, JNK, and
TNF-alpha, and TUNEL was used to mark apoptotic cells in the renal cortex.
RESULTS: The results showed that the highest expression of HMGB1 in muscle was 12
h after CS. JNK and TNF-alpha increased and peaked at 1 day after CS in kidneys.
Western blot analysis revealed that anti-HMGB1 antibody could downregulate the
expression of JNK and TNF-alpha. Anti-TNF-alpha could downregulate activation of
JNK, and SP600125 could downregulate expression of TNF-alpha in the kidneys. In
addition, anti-HMGB1 antibody, anti-TNF-alpha antibody, and SP600125 could reduce
cellular apoptosis in the renal cortex. CONCLUSIONS: It is possible that JNK and
TNF-alpha commonly contribute to kidney damage by assembling a positive feedback
cycle after CS, leading to increased apoptosis in the renal cortex. HMGB1 from
the muscle may be the trigger.
PMID- 28701228
TI - Efficacy of umbilical cord cleansing with a single application of 4%
chlorhexidine for the prevention of newborn infections in Uganda: study protocol
for a randomized controlled trial.
AB - BACKGROUND: Yearly, nearly all the estimated worldwide 2.7 million neonatal
deaths occur in low- and middle-income countries. Infections, including those
affecting the umbilical cord (omphalitis), are a significant factor in
approximately a third of these deaths. In fact, the odds of all-cause mortality
are 46% higher among neonates with omphalitis than in those without. Five large
randomized controlled trials in Asia and Sub-Saharan Africa (SSA) have examined
the effect of multiple cord stump applications with 4% chlorhexidine (CHX) for at
least 7 days on the risk of omphalitis and neonatal death. These studies, all
community-based, show that multiple CHX applications reduced the risk of
omphalitis. Of these trials, only one study from South Asia (the Bangladeshi
study) and none from Africa examined the effect of a single application of CHX as
soon as possible after birth. In this Bangladeshi trial, CHX led to a reduction
in the risk of mild-moderate omphalitis and neonatal death. It is important, in
an African setting, to explore the effect of a single application among health
facility births. A single application is programmatically much simpler to
implement than daily applications for 7 days. Therefore, our study compares
umbilical cord cleansing with a single application of 4% CHX at birth with dry
cord care among Ugandan babies born in health facilities, on the risk of
omphalitis and severe neonatal illness. METHODS: The CHX study is a facility
based, individually randomized controlled trial that will be conducted among 4760
newborns in Uganda. The primary outcomes are severe illness and omphalitis during
the neonatal period. Analysis will be by intention-to-treat. DISCUSSION: This
study will provide novel evidence, from a Sub-Saharan African setting, of the
effect of umbilical cord cleansing with a single application of 4% CHX at birth
and identify modifiable risk factors for omphalitis. TRIAL REGISTRATION:
ClinicalTrials.gov, identifier: NCT02606565 . Registered on 12 November 2015.
PMID- 28701230
TI - Plasmid composition in Aeromonas salmonicida subsp. salmonicida 01-B526 unravels
unsuspected type three secretion system loss patterns.
AB - BACKGROUND: Aeromonas salmonicida subsp. salmonicida is a ubiquitous
psychrophilic waterborne bacterium and a fish pathogen. The numerous mobile
elements, especially insertion sequences (IS), in its genome promote
rearrangements that impact its phenotype. One of the main virulence factors of
this bacterium, its type three secretion system (TTSS), is affected by these
rearrangements. In Aeromonas salmonicida subsp. salmonicida most of the TTSS
genes are encoded in a single locus on a large plasmid called pAsa5, and may be
lost when the bacterium is cultivated at a higher temperature (25 degrees C),
producing non-virulent mutants. In a previous study, pAsa5-rearranged strains
that lacked the TTSS locus on pAsa5 were produced using parental strains,
including 01-B526. Some of the generated deletions were explained by homologous
recombination between ISs found on pAsa5, whereas the others remained unresolved.
To investigate those rearrangements, short- and long-read high-throughput
sequencing technologies were used on the A. salmonicida subsp. salmonicida 01
B526 whole genome. RESULTS: Whole genome sequencing of the 01-B526 strain
revealed that its pAsa5 has an additional IS copy, an ISAS5, compared to the
reference strain (A449) sequence, which allowed for a previously unknown
rearrangement to occur. It also appeared that 01-B526 bears a second large
plasmid, named pAsa9, which shares 40 kbp of highly similar sequences with pAsa5.
Following these discoveries, previously unexplained deletions were elucidated by
genotyping. Furthermore, in one of the derived strains a fusion of pAsa5 and
pAsa9, involving the newly discovered ISAS5 copy, was observed. CONCLUSION: The
loss of TTSS and hence virulence is explained by one consistent mechanism: IS
driven homologous recombination. The similarities between pAsa9 and pAsa5 also
provide another example of genetic diversity driven by ISs.
PMID- 28701231
TI - Immune evasion might affect survival in laryngeal cancer patients with blood
group O.
PMID- 28701232
TI - The three paradoxes of patient flow: an explanatory case study.
AB - BACKGROUND: Health systems in many jurisdictions struggle to reduce Emergency
Department congestion and improve patient flow across the continuum of care. Flow
is often described as a systemic issue requiring a "system approach"; however,
the implications of this idea remain poorly understood. Focusing on a Canadian
regional health system whose flow problems have been particularly intractable,
this study sought to determine what system-level flaws impede healthcare
organizations from improving flow. METHODS: This study drew primarily on
qualitative data from in-depth interviews with 62 senior, middle and departmental
managers representing the Region, its programs and sites; quantitative analysis
of key flow indicators (1999-2012) and review of ~700 documents furnished
important context. Examination of the interview data revealed that the most
striking feature of the dataset was contradiction; accordingly, a technique of
dialectical analysis was developed to examine observed contradictions at
successively deeper levels. RESULTS: Analysis uncovered three paradoxes: "Many
Small Successes and One Big Failure" (initiatives improve parts of the system but
fail to fix underlying system constraints); "Your Innovation Is My Aggravation"
(local innovation clashes with regional integration); and most critically, "Your
Order Is My Chaos" (rules that improve service organization for my patients
create obstacles for yours). This last emerges when some entities
(sites/hospitals) define their patients in terms of their location in the system,
while others (regional programs) define them in terms of their
needs/characteristics. As accountability for improving flow was distributed among
groups that thus variously defined their patients, local efforts achieved little
for the overall system, and often clashed with each other. These paradoxes are
indicative of a fundamental antagonism between the system's parts and the whole.
CONCLUSION: An accretion of flow initiatives in all parts of the system will
never add up to a system approach, and may indeed perpetuate the paradoxes. What
is needed is a coherent strategy of defining patient populations by needs,
analyzing their entire trajectories of care, and developing consistent processes
to better meet those needs.
PMID- 28701233
TI - Bereavement support standards and bereavement care pathway for quality palliative
care.
AB - : ABSTRACTObjective:Provision of bereavement support is an essential component of
palliative care service delivery. While bereavement support is integral to
palliative care, it is typically insufficiently resourced, under-researched, and
not systematically applied. Our aim was to develop bereavement standards to
assist palliative care services to provide targeted support to family caregivers.
METHOD: We employed a multiple-methods design for our study, which included: (1)
a literature review, (2) a survey of palliative care service providers in
Australia, (3) interviews with national (Australian) and international experts,
(4) key stakeholder workshops, and (5) a modified Delphi-type survey. RESULTS: A
total of 10 standards were developed along with a pragmatic care pathway to
assist palliative care services with implementation of the standards.
SIGNIFICANCE OF RESULTS: The bereavement standards and care pathway constitute a
key initiative in the evolution of bereavement support provided by palliative
care services. Future endeavors should refine and examine the impact of these
standards. Additional research is required to enhance systematic approaches to
quality bereavement care.
PMID- 28701234
TI - Opinion paper: Are we on the right track toward livestock sector sustainability?
PMID- 28701235
TI - Analyses of reaction norms reveal new chromosome regions associated with tick
resistance in cattle.
AB - Despite single nucleotide polymorphism (SNP) availability and frequent cost
reduction has allowed genome-wide association studies even in complex traits as
tick resistance, the use of this information source in SNP by environment
interaction context is unknown for many economically important traits in cattle.
We aimed at identifying putative genomic regions explaining differences in tick
resistance in Hereford and Braford cattle under SNP by environment point of view
as well as to identify candidate genes derived from outliers/significant markers.
The environment was defined as contemporary group means of tick counts, since
they seemed to be the most appropriate entities to describe the environmental
gradient in beef cattle. A total of 4363 animals having tick counts (n=10 673)
originated from 197 sires and 3966 dams were used. Genotypes were acquired on
3591 of these cattle. From top 1% SNPs (410) having the greatest effects in each
environment, 75 were consistently relevant in all environments, which indicated
SNP by environment interaction. The outliers/significant SNPs were mapped on
chromosomes 1, 2, 5, 6, 7, 9, 11, 13, 14, 15, 16, 18, 21, 23, 24, 26 and 28, and
potential candidate genes were detected across environments. The presence of SNP
by environment interaction for tick resistance indicates that genetic expression
of resistance depends upon tick burden. Markers with major portion of genetic
variance explained across environments appeared to be close to genes with
different direct or indirect functions related to immune system, inflammatory
process and mechanisms of tissue destruction/repair, such as energy metabolism
and cell differentiation.
PMID- 28701236
TI - Short communication: insoluble fibres in supplemental pre-weaning diets affect
behaviour of suckling piglets.
AB - We investigated the effect of offering supplementary dietary fibres to suckling
piglets on their behaviour and performance before weaning. From 5 to 22 days of
age, suckling piglets were offered a high-fibre diet (HF; 5% cellulose; n=5
litters), or a control low-fibre diet (n=5 litters). Piglets were housed with the
sows in individual farrowing pens, and had access to maternal milk until weaning,
at 23 days of age. Behaviours of six focal piglets per pen were scored at 6, 16
and 21 days of age. All piglets were individually weighed at 5, 15 and 20 days of
age and feed intake was measured daily at the pen level. Piglets on the HF diet
were more active than controls (P=0.05), and spent more time suckling or
massaging the udder (P=0.01) and interacting with pen mates (P=0.008). Time spent
manipulating pen mates, which may reflect re-directed foraging activity in the
absence of substrate, accounted for most of the time spent interacting with pen
mates (?73% of total time spent interacting). Dietary fibres had no effect on BW
and feed intake. In conclusion, inclusion of cellulose in the supplemental diet
of suckling piglets affects behaviour, with no deleterious effects on performance
before weaning.
PMID- 28701237
TI - Flow cytometric sex sorting affects CD4 membrane distribution and binding of
exogenous DNA on bovine sperm cells.
AB - Bovine sex-sorted sperm have been commercialized and successfully used for the
production of transgenic embryos of the desired sex through the sperm-mediated
gene transfer (SMGT) technique. However, sex-sorted sperm show a reduced ability
to internalize exogenous DNA. The interaction between sperm cells and the
exogenous DNA has been reported in other species to be a CD4-like molecule
dependent process. The flow cytometry-based sex-sorting process subjects the
spermatozoa to different stresses causing changes in the cell membrane. The aim
of this study was to elucidate the relationship between the redistribution of CD4
like molecules and binding of exogenous DNA to sex-sorted bovine sperm. In the
first set of experiments, the membrane phospholipid disorder and the
redistribution of the CD4 were evaluated. The second set of experiments was
conducted to investigate the effect of CD4 redistribution on the mechanism of
binding of exogenous DNA to sperm cells and the efficiency of lipofection in sex
sorted bovine sperm. Sex-sorting procedure increased the membrane phospholipid
disorder and induced the redistribution of CD4-like molecules. Both X-sorted and
Y-sorted sperm had decreased DNA bound to membrane in comparison with the
unsorted sperm; however, the binding of the exogenous DNA was significantly
increased with the addition of liposomes. Moreover, we demonstrated that the
number of sperm-bound exogenous DNA was decreased when these cells were
preincubated with anti-bovine CD4 monoclonal antibody, supporting our hypothesis
that CD4-like molecules indeed play a crucial role in the process of exogenous
DNA/bovine sperm cells interaction.
PMID- 28701238
TI - Cognitive stimulation therapy in dementia care: exploring the views and
experiences of service providers on the barriers and facilitators to
implementation in practice using Normalization Process Theory.
AB - BACKGROUND: Cognitive stimulation therapy (CST) is an evidence-based, cost
effective psychosocial intervention for people with dementia but is currently not
a standard part of post-diagnostic care. This qualitative study explored the
views and experiences of dementia care providers on the barriers and facilitators
to its implementation in usual care. METHOD: Thirty four semi-structured
interviews (24 participants) were conducted across four dementia care sites in
the North of England; ten were follow-up interviews. Data were analyzed using
thematic analysis and then mapped to the Normalization Process Theory framework.
RESULTS: Participants considered CST a "good fit" with their "preferred" ways of
working and goals of dementia care namely the provision of person-centered
services. For facilitators delivering the intervention, compared to other
behavioral interventions, CST was seen to offer benefits to their work and was
easy to understand as an intervention. Training in CST and seeing benefits for
clients were important motivators. Time and resources were crucial for the
successful implementation of CST. Participants were keen to objectively measure
benefits to participants but unsure how to do this. CONCLUSIONS: CST is a cost
effective psychosocial intervention for people with dementia, recommended by
national guidance. Despite our findings which show that, using the NPT framework,
there are more facilitators than barriers to the implementation of CST, it is
still not a standard part of post-diagnostic dementia care. Further research is
needed to explore the reasons for this implementation gap in ensuring evidence
based care in translated into practice.
PMID- 28701239
TI - The role of primary care in identification and ongoing management of dementia: a
time of transition.
AB - In this edition of International Psychogeriatrics, Pertrazzuoli et al. (2017)
address attitudes to dementia by primary care physicians (PCPs) across a range of
European countries. The article focusses on diagnosis, screening instruments and
drug treatment, and finds a wide range of approaches to the PCPs' role in
referral for diagnosis and medication prescription. The findings include that
PCPs who are allowed to prescribe dementia drugs, engage in higher levels of
diagnostic work up, despite all the barriers to identification ably summarized in
the paper. Perhaps, this heterogeneity is not random: it may be that roles and
responsibilities for PCPs in relation to dementia are in transition.
PMID- 28701240
TI - Modelling the influence of host community composition in a sylvatic Trypanosoma
cruzi system.
AB - Species composition of wild reservoir hosts can influence the transmission and
maintenance of multi-host vector borne pathogens. The 'pace of life' hypothesis
proposes that the life history strategy of reservoir hosts can influence pathogen
transmission of vector borne generalist pathogens. We use empirical data to
parameterize a mathematical model that investigates the impacts of host life
history traits on vector transmission dynamics of the vector-borne multi-host
parasite Trypanosoma cruzi in habitats characterized by different degrees of
deforestation and varying host community structure. The model considers
susceptible and infected vector and host populations. When comparing the
proportion of vectors infected with T. cruzi predicted by the model with
empirical data, we found a trend of increasing vector infection as anthropogenic
landscape disturbance increases for both data and model output. The model's
vector infection rates were significantly lower than empirical results, but when
incorporating host congenital transmission in the model, vector infection
approaches field data. We conclude that intervened habitats associated with r
selected host species communities predict higher proportions of infected vectors.
PMID- 28701241
TI - Arginine metabolism and its protective effects on intestinal health and functions
in weaned piglets under oxidative stress induced by diquat.
AB - The intestine plays key roles in maintaining body arginine (Arg) homoeostasis.
Meanwhile, the intestine is very susceptible to reactive oxygen species. In light
of this, the study aimed to explore the effects of Arg supplementation on
intestinal morphology, Arg transporters and metabolism, and the potential
protective mechanism of Arg supplementation in piglets under oxidative stress. A
total of thirty-six weaned piglets were randomly allocated to six groups with six
replicates and fed a base diet (0.95 % Arg,) or base diet supplemented with 0.8 %
and 1.6 % l-Arg for 1 week, respectively. Subsequently, a challenge test was
conducted by intraperitoneal injection of diquat, an initiator of radical
production, or sterile saline. The whole trial lasted 11 d. The diquat challenge
significantly decreased plasma Arg concentration at 6 h after injection (P<0.05),
lowered villus height in the jejunum and ileum (P<0.05) as well as villus width
and crypt depth in the duodenum, jejunum and ileum (P<0.05). Oxidative stress
significantly increased cationic amino acid transporter (CAT)-1, CAT-2 and CAT-3,
mRNA levels (P<0.05), decreased arginase II (ARGII) and inducible nitric oxide
synthase mRNA levels, and increased TNF- alpha mRNA level in the jejunum
(P<0.05). Supplementation with Arg significantly decreased crypt depth (P<0.05),
suppressed CAT-1 mRNA expression induced by diquat (P<0.05), increased ARGII and
endothelial nitric oxide synthase mRNA levels (P<0.05), and effectively relieved
the TNF- alpha mRNA expression induced by diquat in the jejunum (P<0.05). It is
concluded that oxidative stress decreased Arg bioavailability and increased
expression of inflammatory cytokines in the jejunum, and that Arg supplementation
has beneficial effects in the jejunum through regulation of the metabolism of Arg
and suppression of inflammatory cytokine expression in piglets.
PMID- 28701242
TI - Feeling useful and engaged in daily life: exploring the experiences of people
with young-onset dementia.
AB - BACKGROUND: To explore the aspects of daily life that give people with young
onset dementia (YOD) a sense of usefulness. METHODS: Eighteen people with YOD and
21 informal caregivers participated in this qualitative study. Participants were
recruited from specialized day-care centers for people with YOD in the
Netherlands. Four focus groups were conducted with people with YOD, and four with
informal caregivers. Focus groups were audio-recorded, transcribed, and analyzed
using inductive content analysis. RESULTS: Four themes emerged from the analysis:
(1) staying engaged, (2) loss in daily life, (3) coping and adaptation, and (4)
external support. Staying engaged in activities that provide a sense of
usefulness or participating in leisure and recreational activities as much as
possible in daily life emerged as the key theme. Retaining a sense of usefulness
was considered both important and possible by having social roles or
participating in functional activities. The importance of activities providing a
sense of usefulness seemed to decrease over time, while the need for pleasant
activities seemed to increase. Experienced loss, coping, adaptation, and
available external support are important parts of the context in which the person
with YOD tries to engage in daily life as much as possible. Active coping styles
and external support appear to play a facilitating role in staying engaged.
CONCLUSIONS: It is important for people with YOD to have the opportunity to feel
useful; especially in the early stages of the condition. Caregivers should be
educated in ways to enhance a sense of usefulness and engagement in daily life
for people with YOD.
PMID- 28701243
TI - Regulation of fetuin A gene expression in the neonatal pig liver.
AB - Fetuin A (also known as alpha2-Heremans-Schmid glycoprotein) is a protein
primarily expressed by the liver and secreted into the blood. Previous studies
have suggested that plasma concentrations of fetuin A are elevated with impaired
growth rate in swine. The present study was designed to examine the relationship
of porcine fetuin A with growth rate in the pig and to also elucidate the
regulation of fetuin A expression by examining the hormonal and cytokine
regulation of fetuin A mRNA abundance in hepatocytes prepared from suckling
piglets. Quantitative real-time PCR assay was used to quantify the number of
fetuin A mRNA molecules/molecule cyclophilin mRNA. Total RNA was isolated from
liver of three different groups of pigs to assess changes in mRNA abundance of
fetuin A: normal piglets at day 1, day 7 day 21 or 6 months of age (n=6 for each
age); runt and control piglets at day 1 of age (n=4); slow growing and normal
growing piglets at 21 days of age (n=8). Following birth, fetuin A gene
expression increased from day 1 and 7 of age (P<0.05), and then declined at 21
days of age (P<0.05), with a much greater decline to 6 months of age (P<0.01).
Fetuin A mRNA abundance was higher in runt pigs v. their normal birth weight
littermates (P<0.05). Similarly, fetuin A gene expression was higher in livers of
pigs that were born at a normal weight but that grew much slower than littermates
with the same birth weight (P<0.05). Hepatocytes were isolated from preweaned
piglets and maintained in serum-free monolayer culture for up to 72 h to permit
examination of the influences of hormones, cytokines and redox modifiers on
fetuin A mRNA abundance. Fetuin A gene expression was enhanced by glucagon, T3
and resveratrol (P<0.05). Growth hormone, cytokines (interleukin6, tumor necrosis
factor-alpha) and antioxidants (N-acetylcysteine, quercertin) reduced fetuin A
mRNA abundance (P<0.05). A role for fetuin A in postnatal development is
suggested by the differences in fetuin A mRNA abundance between runt piglets or
slow growing piglets and their normal growing sized littermates. The hepatocyte
experiments suggest multiple hormones and cytokines may contribute to the
regulation of fetuin A during early growth of the pig.
PMID- 28701244
TI - Diffuse soft tissue emphysema after dental procedure.
PMID- 28701245
TI - Parental coping in the context of having a child who is facing death: A
theoretical framework.
AB - : ABSTRACTObjective:While improvements in healthcare have resulted in children
with complex and life-threatening conditions living longer, a proportion of them
still die. The death of a child puts parents at increased risk for anxiety,
depression, and complicated grief. Increasing our understanding of the coping
strategies that parents use under such extreme circumstances will enable us to
best provide support to families, before and after a child's death. Our aim
herein was to develop a theoretical framework of parental coping. METHOD:
Evidence from the literature was employed to develop a theoretical framework to
describe parental coping in the context of having a child with a life-limiting
illness who is declining and facing eventual death. RESULTS: The reasoning and
argument consists of three guiding elements: (1) the importance of approach as
well as avoidance (as coping strategies) in the context of managing the extreme
emotions; (2) the importance of the social aspect of coping within a family,
whereby parents cope for others as well as for themselves; and (3) the importance
of a flexible and balanced coping profile, with parents using different coping
strategies simultaneously. Central to the proposed framework is that effective
coping, in terms of adjustment, is achieved by balancing coping strategies:
accessing different coping strategies simultaneously or in parallel with a
specific focus on (1) approach and avoidance and (2) coping aimed at self and
others. SIGNIFICANCE OF RESULTS: Understanding of parental coping strategies is
essential for health professionals in order to support parents effectively.
PMID- 28701246
TI - The influence of gentle interactions with an experimenter during milking on dairy
cows' avoidance distance and milk yield, flow and composition.
AB - Cattle's relationship with humans is a crucial factor regarding their welfare. In
dairy cows, interactions with humans occur regularly during milking. We tested
the effect of gentle interactions (stroking, talking in a gentle voice) during
milking on avoidance distance and milk composition, yield and flow
characteristics as well as behaviour during milking. Over the course of 15 days,
an experimenter interacted gently with 14 German Holstein cows for 2 min during
morning and evening milkings, totalling 60 min; the experimenter stayed at a
similar distance to 12 control cows of the same breed for the same amount of
time. There were no significant differences between the groups in behaviour
during milking. Over the course of the experimental phase, avoidance distance at
the feeding rack decreased significantly in stroked but not in control cows. The
treatment did not improve any of the measures of milk composition, yield or flow;
on the 1st day of the treatment, milk ejection was impaired in stroked cows,
which points towards an effect of the novelty of the treatment. We conclude that
gentle interactions during milking improve the relationship between cows and a
human. Possible reasons for the absence of an effect on milk characteristics are
that cows may not have perceived the interactions as positive or that a ceiling
effect occurred due to otherwise optimal milking routines.
PMID- 28701247
TI - The effect of dietary addition of nitrate or increase in lipid concentrations,
alone or in combination, on performance and methane emissions of beef cattle.
AB - Adding nitrate to or increasing the concentration of lipid in the diet are
established strategies for reducing enteric methane (CH4) emissions, but their
effectiveness when used in combination has been largely unexplored. This study
investigated the effect of dietary nitrate and increased lipid included alone or
together on CH4 emissions and performance traits of finishing beef cattle. The
experiment was a 2*4 factorial design comprising two breeds (cross-bred Aberdeen
Angus (AAx) and cross-bred Limousin (LIMx) steers) and four dietary treatments
(each based on 550 g forage : 450 g concentrate/kg dry matter (DM)). The four
dietary treatments were assigned according to a 2*2 factorial design where the
control treatment contained rapeseed meal as the main protein source, which was
replaced either with nitrate (21.5 g nitrate/kg DM); maize distillers dark grains
(MDDG, which increased diet ether extract from 24 to 37 g/kg DM) or both nitrate
and MDDG. Steers (n=20/dietary treatment) were allocated to each of the four
treatments in equal numbers of each breed with feed offered ad libitum. After 28
days adaptation to dietary treatments, individual animal intake, performance and
feed efficiency were recorded for 56 days. Thereafter, CH4 emissions were
measured over 13 weeks (six steers/week). Increasing dietary lipid did not
adversely affect animal performance and showed no interactions with dietary
nitrate. In contrast, addition of nitrate to diets resulted in poorer live-weight
gain (P<0.01) and increased feed conversion ratio (P<0.05) compared with diets
not containing nitrate. Daily CH4 output was lower (P<0.001) on nitrate
containing diets but increasing dietary lipid resulted in only a non-significant
reduction in CH4. There were no interactions associated with CH4 emissions
between dietary nitrate and lipid. Cross-bred Aberdeen Angus steers achieved
greater live-weight gains (P<0.01), but had greater DM intakes (P<0.001), greater
fat depth (P<0.01) and poorer residual feed intakes (P<0.01) than LIMx steers.
Cross-bred Aberdeen Angus steers had higher daily CH4 outputs (P<0.001) but
emitted less CH4 per kilogram DM intake than LIMx steers (P<0.05). In conclusion,
inclusion of nitrate reduced CH4 emissions in growing beef cattle although the
efficacy of nitrate was less than in previous work. When increased dietary lipid
and nitrate inclusion were combined there was no evidence of an interaction
between treatments and therefore combining different nutritional treatments to
mitigate CH4 emissions could be a useful means of achieving reductions in CH4
while minimising any adverse effects.
PMID- 28701248
TI - Rethinking Adverse Drug Events.
PMID- 28701249
TI - Joseph Gruber: A Passion for Geriatrics.
PMID- 28701250
TI - The Ketogenic Diet: Making a Comeback.
AB - Americans have embraced a large number of diets in an attempt to manage obesity,
improve quality of life, and address specific health problems. Among diets
developed to address health problems, the ketogenic diet has had a long and
variable history. Developed in the 1920s by a faith healer to help children with
epilepsy, this diet induces a state that mimics carbohydrate starvation. As
medications became available and effectively addressed seizures, the diet fell
out of favor. During the last few decades, researchers and clinicians have
learned that it can be useful in children and adults with refractory epilepsy and
a variety of other conditions. Once again, pharmacists may encounter patients who
are employing dietary management of serious health problems. This very high-fat
diet almost eliminates carbohydrates from the patient's food selection. The
result is the substitution of ketone bodies as a source of energy. Today's
ketogenic diet has been modified with scientifically proven adjustments to
increase palatability and help with adherence. Effective for some forms of
epilepsy, the ketogenic diet also seems to have some utility in Alzheimer's
disease, Parkinson's disease, and glaucoma, and many Americans are using it to
lose weight. Consultant pharmacists may field questions about this diet, its
potential to correct or alleviate health conditions, and its limitations. The
article discusses the ketogenic diet's strengths, limitations, potential
mechanisms, and use in a number of conditions with an emphasis on the elderly.
PMID- 28701251
TI - Recognition and Management of Anaphylaxis in Older Adults.
AB - OBJECTIVES: To discuss medications that cause anaphylaxis in older adults and its
treatment, with a focus on epinephrine. DATA SOURCE: A search of PubMed using the
terms "anaphylaxis," "drug-induced anaphylaxis," "epinephrine autoinjectable,"
"anaphylaxis diagnosis," "anaphylaxis treatment," and "epinephrine cost" was
performed. English-language articles from January 2000 to August 2016 appearing
in these searches were reviewed. STUDY SELECTION/DATA EXTRACTION: Relevant review
articles, consensus statements, practice parameters, task force recommendations,
and original articles were assessed for recognition and treatment of drug-induced
anaphylaxis. DATA SYNTHESIS: Anaphylaxis is a serious allergic reaction that
occurs with food, insect stings, latex, radio contrast agents, and medications.
Medications that are commonly used by older adults can cause anaphylaxis.
Epinephrine remains the first-line treatment option and does not have any
contraindications. CONCLUSION: Early recognition of drug-induced anaphylaxis
symptoms is critical and medication should be administered immediately to prevent
cardiac arrest. Additionally, health care providers can provide others with
education on administration of epinephrine auto-injectable agents, availability
of alternative options, and patient-assistance programs to lower the cost of
epinephrine agents.
PMID- 28701252
TI - Idiopathic Pulmonary Fibrosis: A Case Discussion.
AB - OBJECTIVE: The purpose of this report is to describe the case of a 68-year-old
man who was treated for idiopathic pulmonary fibrosis (IPF), a chronic and fatal
lung disease that is characterized by progressive deterioration of pulmonary
function. He was initially prescribed pirfenidone and developed significant
gastric distress. The treatment was transitioned to nintedanib. This article will
provide the pharmacist with a therapeutic overview of IPF, as well as review the
unique process involved with drug acquisition, dosing, patient education, and
monitoring of pirfenidone and nintedanib. SETTINGS: Community pharmacy, nursing
facility pharmacy, consultant pharmacy practice. PRACTICE CONSIDERATIONS:
Pirfenidone and nintedanib are the only medications in the United States approved
to treat IPF. These treatments have distinctive properties that differ from past
therapies for IPF. CONCLUSION: It is important for pharmacists to understand the
treatment recommendations for IPF and to review the process for acquisition,
dosing, and administration of pirfenidone and nintedanib to better assist
physicians and patients and improve therapeutic outcomes.
PMID- 28701253
TI - A Brief Review of Three Common Supplements Used in Alzheimer's Disease.
AB - Individuals with Alzheimer's disease (AD) and their caregivers are using
supplements in an effort to halt the progression of the disease. Individuals at
risk for or fearing Alzheimer's may use these supplements to try to prevent the
disease. Senior care pharmacists are accessible and uniquely qualified to answer
questions, make recommendations, and attempt to make drug therapy safe and
effective for these individuals. With this in mind, it is important to know the
data supporting (or not supporting) common supplements marketed toward those with
AD. A review of efficacy and safety data, drug interactions, as well as the
mechanism of action believed to benefit those with AD of three common supplements
(Prevagen, Cerefolin NAC, and the omega-3 polyunsaturated fatty acid DHA), are
highlighted.
PMID- 28701254
TI - Characteristics of Older Adults Who Consume Alcohol While on Antidepressants.
AB - OBJECTIVES: Determine the characteristics of older Americans who self-report
consuming alcohol and taking at least one antidepressant. DESIGN: This study
utilized cross-sectional analyses. SETTING: The University of Michigan Health and
Retirement Study and its subsurvey Prescription Drug Study (PDS). PATIENTS,
PARTICIPANTS: Those who reported taking at least one antidepressant prescription
medication, were 65 years of age or older, and were enrolled in Medicare or
Medicaid between 2002 and 2004. INTERVENTIONS: Chi-square tests were conducted
between demographic groups and alcohol consumption variables. Relationships
between antidepressant quantity and behaviors of those consuming alcohol while
taking antidepressants were also addressed. MAIN OUTCOME MEASURES: Demographics,
alcohol consumption, number of antidepressants, psychiatric problem status, and
alcohol behaviors. RESULTS: There were 412 subjects from the 2007 PDS (N = 3,536)
who self-reported taking at least one antidepressant prescription medication. A
total of 102 (24.8%) of the 412 subjects taking antidepressants reported using
alcohol. Ethnicity, education level attained, and geographic region all showed a
statistical difference between alcohol drinkers and nondrinkers. Most subjects
were only on one antidepressant medication. Also, none of the subjects felt they
needed to cut down on their drinking though they also did not feel annoyed by
criticism from others about their drinking habits. CONCLUSION: This study showed
that 24.8% of older Americans in the community were consuming some amount of
alcohol while on antidepressants. These results show that there is an opportunity
for consultant pharmacists to educate older American adults about the safety
concerns with alcohol consumption and antidepressant use.
PMID- 28701255
TI - ASCP Members Advocate for Society Priorities.
PMID- 28701256
TI - Toll-like receptor expression patterns in the rat uterus during post partum
involution.
AB - Toll-like receptors (TLRs) belong to a family of pathogen recognition receptors
and play critical roles in detecting and responding to invading pathogens. TLR
expression could be significant because, in the uterus, the reproductive tract is
an important site of exposure to and infection by pathogens during the post
partum involution period. To clarify the expression and localisation patterns of
TLRs in the rat uterus on Days 1, 3, 5 and 10 post partum (PP1, PP3, PP5 and PP10
respectively), immunohistochemistry and western blotting were used to analyse
TLR1-7, TLR9 and TLR10. The immunohistochemistry results indicated that TLR1-7,
TLR9 and TLR10 were localised in both the cytoplasm and nuclei of luminal and
glandular epithelium, stromal fibroblasts and myometrial cells in the rat uterus.
In the luminal epithelium, TLR4-7 were also found in lateral membranes, whereas
TLR10 was present in apical membranes. Western blot analysis revealed that the
expression of TLR proteins increased with the number of days post partum,
reaching a maximum on PP10, although levels did not differ significantly from
those on PP1 (P>0.05). These findings confirm that TLR1-7, TLR9 and TLR10 are
constitutively expressed in uterine cells and that localisation pattern of TLRs
in the endometrium varies with structural changes in the uterus on different days
of involution. These results suggest that TLRs may play a role in uterine repair
and remodelling during physiological involution.
PMID- 28701257
TI - Physician testing for HIV in patients treated with tenofovir disoproxil fumarate
and lamivudine monotherapy for hepatitis B virus.
AB - Previously we found that local patients were often not tested for HIV prior to
commencing nucleoside/nucleotide reverse transcription inhibitor (NRTI) therapy
for hepatitis B virus. We performed a national cross-sectional cohort study of
physician practices via an online survey. A small majority (23/44; 52%) of
participants reported always testing their hepatitis B virus patients for HIV
prior to NRTI therapy, and 8/44 (18%) reported testing for HIV the majority of
the time. Thirteen (30%) respondents reported testing only if risk factors were
present. One physician reported a patient seroconverting to HIV while on TDF
monotherapy.
PMID- 28701258
TI - Cultural competence in the community health context: 'we don't have to reinvent
the wheel'.
AB - Health and social service agencies need to be responsive to the healthcare
requirements of culturally and linguistically diverse (CALD) groups in the
community. This is a challenging proposition, particularly due to shifting
demographics in developed Western countries such as Australia. Organisations that
strive for cultural competence can potentially reduce the barriers associated
with inequitable access to services by CALD groups. Community health services
play a vital role in the provision of culturally competent health services to
people from CALD groups. Additional research related to cultural competence in
the community health context is needed. Thus, the aim of this paper is to explore
the positioning of cultural competence within community health from multiple
perspectives using a qualitative case study of a community health service located
in Victoria, Australia. The findings suggest that if the essential needs of
clients are met, regardless of cultural background (e.g. able to communicate with
staff, trust and a respectful and caring environment), then issues related to
cultural background may be of less significance for some clients.
PMID- 28701259
TI - Markers of protein synthesis are increased in fetal membranes and myometrium
after human labour and delivery.
AB - Preterm birth remains one of the leading causes of neonatal death. Inflammation
and maternal infection are two of the leading aetiological factors for preterm
birth. Labour is associated with increased production of proinflammatory
cytokines, chemokines and prolabour mediators in human gestational tissues. In
non-gestational tissues, synthesis of proinflammatory and prolabour mediators is
regulated by components of the protein synthesis machinery. Therefore, in the
present study we investigated the effect of human labour on the expression of
three protein synthesis markers, namely eukaryotic elongation factor 2 kinase
(EEF2K), mitogen-activated protein kinase interacting protein kinase 1 (MKNK1)
and eukaryotic translation initiation factor 4E (EIF4E), and their role in
regulating inflammation in human gestational tissues. In fetal membranes and
myometrium, EEF2K expression was significantly lower, whereas MKNK1 expression
was significantly higher withterm and preterm labourcompared to term nolabour. In
contrast, EIF4E expression did not change in fetal membranes or myometrium with
labour. In primary myometrial cells, loss-of-function studies using specific
chemical inhibitors of EEF2K (A484954) and MKNK1 (CGP57380) demonstrated that
MKNK1, but not EEF2K, was required for polyinosinic-polycytidylic acid
(poly(I:C); a viral double-stranded RNA mimetic) and interleukin (IL)-1beta
induced production of IL6, C-X-C motif chemokine ligand 8 (CXCL8), prostaglandin
endoperoxide synthase 2 (PTGS2) and prostaglandin F2alpha. In conclusion,
spontaneous term and preterm labour is associated with decreased EEF2K and
increased MKNK1 expression in fetal membranes and myometrium. Moreover, MKNK1 is
involved in the genesis of proinflammatory and prolabour mediators that is
mediated by inflammation or infection. However, further studies are required to
elucidate the role of EEF2K in human labour.
PMID- 28701260
TI - Review of early assessment models of innovative medical technologies.
AB - INTRODUCTION: Hospitals increasingly make decisions regarding the early
development of and investment in technologies, but a formal evaluation model for
assisting hospitals early on in assessing the potential of innovative medical
technologies is lacking. This article provides an overview of models for early
assessment in different health organisations and discusses which models hold most
promise for hospital decision makers. METHODS: A scoping review of published
studies between 1996 and 2015 was performed using nine databases. The following
information was collected: decision context, decision problem, and a description
of the early assessment model. RESULTS: 2362 articles were identified and 12
studies fulfilled the inclusion criteria. An additional 12 studies were
identified and included in the review by searching reference lists. The majority
of the 24 early assessment studies were variants of traditional cost
effectiveness analysis. Around one fourth of the studies presented an evaluation
model with a broader focus than cost-effectiveness. Uncertainty was mostly
handled by simple sensitivity or scenario analysis. DISCUSSION AND CONCLUSIONS:
This review shows that evaluation models using known methods assessing cost
effectiveness are most prevalent in early assessment, but seems ill-suited for
early assessment in hospitals. Four models provided some usable elements for the
development of a hospital-based model.
PMID- 28701261
TI - Five-year survival and causes of death in patients on home parenteral nutrition
for severe chronic and benign intestinal failure.
AB - BACKGROUND & AIM: Home parenteral nutrition (HPN) is the primary treatment for
chronic intestinal failure (IF). Intestinal transplantation (ITx) is indicated
when there is an increased risk of death due to HPN complications or to the
underlying disease. Age, pathophysiologic conditions and underlying disease are
known predictors of HPN dependency and overall survival. Although the cause of
death on HPN is mostly related to underlying disease in these patients, the
relationship between mortality and duration of HPN use remains unclear. The
purpose of the present study is to describe factors associated with survival and
HPN dependency as well as causes of death in adult patients requiring HPN for
chronic intestinal failure during the first 5 years of treatment with HPN.
METHODS: A multicenter international (European and USA) questionnaire-based
retrospective follow-up of a cohort of 472 IF patients who started HPN was
conducted between June and December 2000. Study endpoint was either end of 5-year
follow-up, weaned-off HPN, ITx, or death on HPN. Data were analyzed for HPN
dependence and overall survival using Kaplan-Meier models and log rank tests.
RESULTS: The overall survival probability was 88%, 74% and 64% at 1, 3 and 5
years respectively. Survival was inversely related to age (p < .001) and higher
in patients with Crohn's disease or chronic idiopathic pseudo-obstruction. A
total of 169 (36.5%) patients were weaned-off HPN mainly (80%) within the first
year and most frequently in patients with fistulae. Five of the 14 patients who
underwent ITx died. By the end of the study, 104 (23%) of patients died on HPN;
65% of deaths occurred within the first 2.5 years of HPN. CONCLUSIONS: Younger
ages at HPN initiation and underlying pathologies are significantly predictive of
survival on HPN. Risk of death is greatest during the first 2 years of HPN.
PMID- 28701262
TI - Effects of low-dose Bisphenol A on calcium ion influx and on genes of
proliferation and differentiation in immortalized human gingival cells in vitro:
The role of estrogen receptor beta.
AB - OBJECTIVES: Relating to low-dose Bisphenol-A (BPA), there is still a lack of
mechanistic studies in oral cells, representing the first targets of BPA by oral
intake. The objective of this study was to investigate an assumed mechanistic
interrelationship between both low-dose BPA-modulated Calcium ion (Ca2+) influx
and cell behavior, and the estrogen receptor beta (ERbeta), in oral mucosal
cells. METHODS: Indirect immunofluorescence (IIF) was conducted on estrogen
receptor beta (ERbeta) activity after 1, 3, and 6days in response to 39nM BPA,
15MUM BPA, and 200 pM 17beta-Estradiol (E2). In addition to Ca2+ concentration
measurement, qPCR for proliferation and differentiation biomarkers was performed,
to examine cell behavior. Fulvestrant-mediated ER inhibition was employed to seek
for a mechanistic role of ERbeta in regulating BPA-emanating effects. RESULTS:
While both E2 and BPA yielded ERbeta activation, 39nM BPA and 200 pM E2 did not
change MKI67 proliferation marker expression, but reduced transcription of
differentiation markers. Conversely, 15MUM BPA reduced MKI67 transcription, but
significantly increased differentiation gene expression and intracellular Ca2+
levels. Fulvestrant-induced ERbeta inhibition yielded complete elimination of all
E2- and BPA-triggered modulatory effects, suggesting a mechanistic role of
activated ERbeta for BPA-mediated Ca2+ influx and keratinocyte differentiation.
SIGNIFICANCE: Concerning cell behavior, these findings provide significant
evidence of a threshold-dependent transcription of proliferation and
differentiation-related genes as well as Ca2+ influx in response to 39nM and
15MUM low-dose BPA, which identify a mechanistic role of activated ERbeta in oral
keratinocytes.
PMID- 28701264
TI - Impact of rural-urban status on survival after mastectomy without reconstruction
versus mastectomy with reconstruction.
AB - BACKGROUND: Disparities in access to care exist for breast cancer patients,
including access to surgeons performing reconstruction. We hypothesized rural
patients have delayed time to surgery after mastectomy with reconstruction with
implications on survival. METHODS: An observational study was conducted using the
National Cancer Database on patients with breast cancer from 2003 to 2007 who
underwent mastectomy, with or without reconstruction from 2003 to 2007 (n =
90,319). RESULTS: Patients with, and without, reconstruction varied by
demographics, facility type and stage. Time to surgery was longer for mastectomy
with reconstruction. Unadjusted analysis demonstrated marginally decreased
survival for rural patients undergoing mastectomy alone but not for mastectomy
with reconstruction. Cox proportional hazards analysis revealed no significant
differences by rural-urban status, but a survival advantage was seen after
mastectomy with reconstruction, which persisted up to a delay of 180 days.
CONCLUSION: Patients who underwent reconstruction had improved survival. Time to
surgery is shorter for rural patients (for all types of mastectomy). We found no
significant rural-urban disparity in survival.
PMID- 28701263
TI - Treatment for anal fissure: Is there a safe option?
AB - BACKGROUND: Surgeons often approach anal fissure with chemical denervation
(Botulinum toxin, BT) instead of initial lateral internal sphincterotomy (LIS)
due to concerns for long-term incontinence. We evaluated the characteristics and
outcomes of patients who received BT or LIS. METHODS: We performed a
retrospective chart review of patients undergoing LIS and BT for anal fissure
between 2009 and 2015. In 2015, a telephone survey was performed to evaluate
durability, long-term incontinence and patient satisfaction. RESULTS: Ninety-four
patients met criteria: 73 LIS and 21 BT. Age (BT 49 vs. LIS 52) was similar
between groups (p = 1.0). Cleveland Clinic Fecal Incontinence (CCFI) score pre
intervention was higher in BT than LIS patients (2.1 vs. 0.4, p = 0.007) with
fewer BT patients with perfect continence (50% vs. 88%). Telephone survey
response was 61%. Fissure recurrence was significantly higher for BT than LIS
patients (36% vs. 9%, p = 0.03). CONCLUSION: Patients undergoing LIS were less
likely to recur. Both LIS and BT patients had some durable changes in continence
raising the question of whether there is a safe technique.
PMID- 28701265
TI - The measurement frequency and completeness of vital signs in general hospital
wards: An evidence free zone?
PMID- 28701266
TI - Community-acquired bloodstream infections caused by Acinetobacter baumannii: A
matched case-control study.
AB - BACKGROUND: Acinetobacter baumannii is an important nosocomial pathogen
worldwide. Its role in community-acquired infection remains controversial and has
rarely been reported. METHODS: Patients with monobacterial bloodstream infections
caused by genomic species identified A. baumannii, admitted to Taipei Veterans
General Hospital between 1999 and 2010, were selected as cases. Controls were
defined as patients acquiring infection in a healthcare setting and were matched
for age and sex. The clinical, epidemiologic, and microbiological characteristics
of cases and controls were compared. RESULTS: Cases presented with shock more
frequently and had higher APACHE II scores (25 vs 19, p = 0.005). No significant
differences between the two groups were noted in the sources of bloodstream
infection and underlying diseases. Multidrug resistance rates were higher in
nosocomial A. baumannii isolates then in those acquired in the community (81.5%
vs 38.9%, p = 0.002). Patients infected in the community were more likely to
receive appropriate antimicrobial therapy than those with hospital-acquired A.
baumannii (10/18; 55.6% vs 11/54; 20.4%, p = 0.011). Acquisition in the community
(odds ratio [OR] 5.716, 95% confidence interval [CI] 1.021-32.003, p = 0.047),
respiratory tract as the infection source (OR 9.514, 95% CI 2.370-38.189, p =
0.001), and immunosuppressive therapy (OR 4.331, 95% CI 1.052-17.832, p = 0.042)
were independently associated with increased 14-day mortality among patients with
A. baumannii bacteremia in this cohort. CONCLUSION: Community-acquired bacteremia
caused by A. baumannii was rare but associated with a severe outcome. Further
investigation of potential virulence factors of community-acquired A. baumannii
is required.
PMID- 28701267
TI - Development of capillary liquid chromatography: A personal perspective.
AB - This is a historical account on the development of capillary LC from its
beginning to the present day. The first investigations into the viability of
capillary LC date back to the late 1970s, a decade after the pioneering efforts
in HPLC. The drastically reduced column dimensions were required to counter the
slow solute diffusion in liquids. There were numerous instrumental difficulties
with sample introduction and detection in the picoliter or even femtoliter
volumes. High-efficiency separations were needed in the analysis of complex
biological mixtures. Miniaturization brought distinct advantages in spectroscopic
and electrochemical detection. Since the 1980s, column technologies underwent
significant changes: (a) from glass-drawn microcapillaries to slurry-packed,
small-diameter fused silica columns; and (b) in microcapillaries packed
alternatively with sub-2-MUm particles or monoliths. The viability of LC-MS
combination has dramatically promoted the use of small-diameter capillaries.
Through "omics technologies", capillary LC/tandem MS accounts for most
applications in proteomics, glycomics and metabolomics.
PMID- 28701268
TI - Positive emotional well-being, health Behaviors, and inflammation measured by C
Reactive protein.
AB - OBJECTIVE: There is a substantial body of literature describing the association
between inflammatory biomarkers and negative emotional factors (i.e. depression).
However, less is known about how they might be related to positive psychological
variables. This study examined the association between positive emotional well
being (PEWB) and C-Reactive Protein (CRP), an inflammatory biomarker important
for cardiovascular and other diseases. METHOD: Data were analyzed from 1979
respondents to a nationwide survey in the U.S., which included a chronically ill
subgroup. Two aspects of PEWB were assessed; positive affect and life
satisfaction. CRP was analyzed via blood-spot from a finger-prick. The mediating
role of health behaviors (i.e., smoking, alcohol, BMI, and moderate exercise) was
also examined. RESULTS: Both positive affect and life satisfaction were
significantly related to lower CRP even after controlling for demographics and
depression, in both the overall sample and chronically ill group. Only life
satisfaction remained significantly related to CRP when controlling for health
behaviors. When both depression and health behaviors were controlled, neither
positive affect nor life satisfaction was significantly related to CRP. Moderate
exercise emerged as the strongest mediator, followed by BMI and smoking.
Individuals with low positive affect or low life satisfaction were at increased
odds (OR = 1.40 and OR = 1.54, respectively) of having clinically elevated (>=3
mg/L) CRP. CONCLUSION: Our results add to a growing literature reporting an
association between aspects of PEWB, especially life satisfaction, and a health
related biomarker of inflammation. Those with low positive affect or life
satisfaction face increased risk of having clinically elevated CRP. Health
behaviors, especially BMI and moderate exercise, account for some but not all of
this relationship. Future studies should determine whether increasing life
satisfaction and positive affect may contribute to improvements in health
behaviors, inflammation, and better health outcomes.
PMID- 28701269
TI - Retraction notice to "Abduction external rotation position in magnetic resonance
arthrography for the diagnosis of rotator cuff tears" [J Orthop Sci 21 (2016) 446
451].
PMID- 28701270
TI - Mycoplasma genitalium: yet another challenging STI.
PMID- 28701271
TI - Health systems and the new strategy against sexually transmitted infections.
PMID- 28701272
TI - Sexually transmitted infections: challenges ahead.
AB - WHO estimated that nearly 1 million people become infected every day with any of
four curable sexually transmitted infections (STIs): chlamydia, gonorrhoea,
syphilis, and trichomoniasis. Despite their high global incidence, STIs remain a
neglected area of research. In this Commission, we have prioritised five areas
that represent particular challenges in STI treatment and control. Chlamydia
remains the most commonly diagnosed bacterial STI in high-income countries
despite widespread testing recommendations, sensitive and specific non-invasive
testing techniques, and cheap effective therapy. We discuss the challenges for
chlamydia control and evidence to support a shift from the current focus on
infection-based screening to improved management of diagnosed cases and of
chlamydial morbidity, such as pelvic inflammatory disease. The emergence and
spread of antimicrobial resistance in Neisseria gonorrhoeae is globally
recognised. We review current and potential future control and treatment
strategies, with a focus on novel antimicrobials. Bacterial vaginosis is the most
common vaginal disorder in women, but current treatments are associated with
frequent recurrence. Recurrence after treatment might relate to evidence that
suggests sexual transmission is integral to the pathogenesis of bacterial
vaginosis, which has substantial implications for the development of effective
management approaches. STIs disproportionately affect low-income and middle
income countries. We review strategies for case management, focusing on point-of
care tests that hold considerable potential for improving STI control. Lastly,
STIs in men who have sex with men have increased since the late 1990s. We discuss
the contribution of new biomedical HIV prevention strategies and risk
compensation. Overall, this Commission aims to enhance the understanding of some
of the key challenges facing the field of STIs, and outlines new approaches to
improve the clinical management of STIs and public health.
PMID- 28701273
TI - Turning the spotlight on sexually transmitted infections.
PMID- 28701274
TI - Challenges in responses to syphilis epidemic.
PMID- 28701275
TI - Is going into stable symptomatic remission associated with a more positive
development of life satisfaction? A 10-year follow-up study of first episode
psychosis.
AB - BACKGROUND: Quality of life is an important outcome measure for patients with
psychosis. We investigated whether going into stable symptomatic remission is
associated with a more positive development of subjective quality of life (S-QoL)
and if different patient characteristics are associated with S-QoL depending on
remission status. METHODS: Three hundred and one patients with a first-episode
psychosis were included at baseline. At 10-year follow-up 186 were reassessed.
QoL was assessed by Lehman's Quality of Life Interview. Remission was defined
according to criteria proposed by the Remission in Schizophrenia Working Group.
One-way ANOVA, mixed model analysis, bivariate correlations and multiple
regression analyses were performed. RESULTS: Patients going into stable
symptomatic remission showed a more positive S-QoL-development over the follow-up
period and reported higher life satisfaction at 10-year follow-up compared to non
remission. At 10-year follow-up, depressive symptoms and alcohol abuse or
dependence explained a significant amount of variance in S-QoL among patients in
remission. Among patients in non-remission, PANSS excitative component explained
a significant amount of variance in S-QoL. All significant effects were negative.
CONCLUSIONS: Stable symptomatic remission is associated with a more positive
development of overall life satisfaction. Furthermore, different symptoms
influence life satisfaction depending on status of remission. This has important
clinical implications. While patients in remission might need treatment for
depressive symptoms to increase S-QoL, in non-remission measures aiming to
decrease hostility and uncooperativeness should be part of the treatment
approach. Alcohol problems should be treated regardless of remission status.
PMID- 28701276
TI - Medical image classification via multiscale representation learning.
AB - Multiscale structure is an essential attribute of natural images. Similarly,
there exist scaling phenomena in medical images, and therefore a wide range of
observation scales would be useful for medical imaging measurements. The present
work proposes a multiscale representation learning method via sparse autoencoder
networks to capture the intrinsic scales in medical images for the classification
task. We obtain the multiscale feature detectors by the sparse autoencoders with
different receptive field sizes, and then generate the feature maps by the
convolution operation. This strategy can better characterize various size
structures in medical imaging than single-scale version. Subsequently, Fisher
vector technique is used to encode the extracted features to implement a fixed
length image representation, which provides more abundant information of high
order statistics and enhances the descriptiveness and discriminative ability of
feature representation. We carry out experiments on the IRMA-2009 medical
collection and the mammographic patch dataset. The extensive experimental results
demonstrate that the proposed method have superior performance.
PMID- 28701277
TI - The epigenetic architecture at gene promoters determines cell type-specific LPS
tolerance.
AB - Synovial fibroblasts (SF) drive inflammation and joint destruction in chronic
arthritis. Here we show that SF possess a distinct type of LPS tolerance compared
to macrophages and other types of fibroblasts. In SF and dermal fibroblasts,
genes that were non-tolerizable after repeated LPS stimulation included pro
inflammatory cytokines, chemokines and matrix metalloproteinases, whereas anti
viral genes were tolerizable. In macrophages, all measured genes were
tolerizable, whereas in gingival and foreskin fibroblasts these genes were non
tolerizable. Repeated stimulation of SF with LPS resulted in loss of activating
histone marks only in promoters of tolerizable genes. The epigenetic landscape at
promoters of tolerizable genes was similar in unstimulated SF and monocytes,
whereas the basal configuration of histone marks profoundly differed in genes
that were non-tolerizable in SF only. Our data suggest that the epigenetic
configuration at gene promoters regulates cell-specific LPS-induced responses and
primes SF to sustain their inflammatory response in chronic arthritis.
PMID- 28701278
TI - Angiotensin-converting enzyme inhibitors, angiotensin II receptors antagonists,
beta-blockers and ivabradine as supportive therapy in pulmonary hypertension:
Drug safety and tolerability.
PMID- 28701279
TI - Painful rash on hospitalized patient with diabetic ketoacidosis (DKA).
PMID- 28701280
TI - A framework for nucleus and overlapping cytoplasm segmentation in cervical
cytology extended depth of field and volume images.
AB - We propose a framework to detect and segment nuclei and segment overlapping
cytoplasm in cervical cytology images. This is a challenging task due to folded
cervical cells with spurious edges, poor contrast of cytoplasm and presence of
neutrophils and artifacts. The algorithm segments nuclei and cell clumps in
extended depth of field (EDF) images and uses volume images to segment
overlapping cytoplasm. The boundaries are first approximated by a defined
similarity metric and are refined in two steps by reducing concavity, iterative
smoothing and outliers removal. We evaluated our framework on two public datasets
provided in the first and second overlapping cervical cell segmentation
challenges (ISBI 2014 and 2015). The results show that our method outperforms
other state-of-the-art algorithms on both datasets. The results on the ISBI 2014
dataset show that our method missed less than 5% of cells when the pairwise cell
overlapping degree was not higher than 0.3 and it missed only 7% of cells on
average in a dataset of 810 synthetic images with 4860 (overlapping) cells. On
the same dataset, it outperforms other state-of-the-art methods in nucleus
detection with precision 0.961 and recall 0.933. The results on the ISBI 2015
dataset containing real cervical EDF images show that our method misses around
20% of cells in EDF images where a segmentation is considered a miss if it has
dice similarity coefficient not greater than 0.7. The 20% miss rate is around
half of the miss rate of two other recent methods.
PMID- 28701281
TI - Editorial for the special issue of "Computational methods for molecular imaging"
for computerized medical imaging and graphics.
PMID- 28701282
TI - Risk factors for myocardial dysfunction after traumatic brain injury: A one-year
follow-up study.
AB - INTRODUCTION: Traumatic brain injury has been associated with an increased risk
of myocardial dysfunction. Common abnormalities accompanying this pathology
include electrocardiographic abnormalities, elevated creatine kinase levels,
arrhythmias, and pathologic changes of the myocardium. The aim of this study was
to determine if TBI patients have a higher risk of myocardial dysfunction than
the general population and to identify the risk factors of myocardial dysfunction
in TBI patients. PATIENTS AND METHODS: The study sample was drawn from Taiwan's
National Health Insurance Research Database of reimbursement claims, and
comprised 26,860 patients who visited ambulatory care centers or were
hospitalized with a diagnosis of TBI. The comparison group consisted of 134,300
randomly selected individuals. The stratified Fine and Gray regression was
performed to evaluate independent risk factors for myocardial dysfunction in all
patients and to identify risk factors in TBI patients. RESULTS: During a 1-year
follow-up period, 664 patients with TBI and 1494 controls developed myocardial
dysfunction. TBI was independently associated with increased risk of myocardial
dysfunction. Diabetes, hypertension, peptic ulcer disease, chronic liver disease
and chronic renal disease were risk factors of myocardial dysfunction in TBI
patients. CONCLUSIONS: Individuals with TBI are at greater risk of developing
myocardial dysfunction after adjustments for possible confounding factors. Early
monitor should be initiated to decrease disability and dependence in patients
with TBI.
PMID- 28701283
TI - Control of dissolved CH4 in a municipal UASB reactor effluent by means of a
desorption - Biofiltration arrangement.
AB - The direct anaerobic treatment of municipal wastewater represents an adapted
technology to the conditions of developing countries. In order to get an
increased acceptance of this technology, a proper control of dissolved methane in
the anaerobic effluents should be considered, as methane is a potent greenhouse
gas. In this study, a pilot-scale system was operated for 168 days to recover
dissolved methane from an effluent of an upflow anaerobic sludge blanket reactor
and then oxidize it in a compost biofilter. The system operated at a constant air
(0.9 m3/h +/-0.09) and two air-to anaerobic effluent ratio (1:1 and 1:2). In both
conditions (CH4 concentration of 2.7 +/- 0.87 and 4.3% +/- 1.14, respectively)
the desorption column recovered 99% of the dissolved CH4 and approximately 30% +/
8.5 of H2S, whose desorption was limited due to the high pH (>8) of the
effluent. The biofilter removed 70% +/- 8 of the average CH4 load (60 gCH4/m3h +/
13) and 100% of the H2S load at an empty bed retention time of 23 min. The
average temperature inside the biofilter was 42 +/- 9 degrees C due to the CH4
oxidation reaction, indicating that temperature and moisture control is
particularly important for CH4 removal in compost biofilters. The system may
achieve a 54% reduction of greenhouse gas emissions from dissolved CH4 in this
particular case.
PMID- 28701284
TI - Cost-effectiveness analysis of different dipeptidyl-peptidase 4 inhibitor drugs
for treatment of type 2 diabetes mellitus.
AB - INTRODUCTION: Type 2 diabetes mellitus (T2DM) has burdened health systems in the
world to the value of 500 billion dollars/year. Dipeptidyl peptidase 4 inhibitors
(DPP-4 Inhibitors) have been strongly associated with spending on the treatment
of T2DM by the courts in Brazil. The aim of this study was to estimate the most
cost-effective DPP-4 Inhibitor for T2DM treatment. A pharmacoeconomic study of
cost-effectiveness was performed in a medium-sized municipality in Minas Gerais
state, Brazil. METHODS: The data are from legalization in municipal health in
2013. The effectiveness of DPP-4 Inhibitors was measured by the reduction in
glycated hemoglobin (A1c). The direct medical costs of drug and adverse drug
reactions were identified. With these data, a cost-effectiveness ratio (CER) and
construction of the decision tree for sensitivity analysis were performed.
RESULTS: The representative of the most effective in reducing A1c gliptins was
sitagliptin in combination with metformin, it was able to reduce A1c by 1.16%
(1.09 to 1.22, CI 95%). The drug with the lowest cost was linagliptin, with a
cost per patient/year of US$ 481.42. Sensitivity analysis performed by the
decision tree shows that sitagliptin in association with metformin had the CER of
US$ 1,506.75 per patient/year, to reduce A1c by 1%. CONCLUSION: The most cost
effective DPP-4 Inhibitor was sitagliptin with metformin.
PMID- 28701285
TI - Association of divalent cations and insulin resistance with thyroid hormones in
patients with type 2 diabetes mellitus.
AB - AIM: The study was primarily aimed at investigating the association of Magnesium
and Zinc levels in the serum of adult Non- obese and Obese type 2 diabetic
patients, with particular reference to thyroid comorbidity. METHODS: 108 patients
with T2DM of both genders (24 Non obese and 84 Obese) were enrolled from a
tertiary health care unit in Puducherry. The cardio-metabolic risk factors were
assessed through body mass index, Waist hip ratio, blood pressure, fasting blood
glucose, lipid profile and glycated haemoglobin. Zinc and Magnesium were
quantitated. Insulin resistance was by Homeostasis model assessment. Serum free
T4, T3 and TSH were also measured. RESULTS: In non-obese type 2 diabetic group,
Glycated haemoglobin had a strong positive correlation with free T4(r=0.784;
p=0.003).TSH also depicted a positive association with HOMA-IR (r=0.924;
p<0.001); whereas,T3 and Insulin had negative correlation with Magnesium (r=
0.599* and r=-0.620*; p 0.04 and 0.031). The levels of Zinc and Magnesium in the
serum of obese diabetic patients had a positive correlation among them (r=0.565#;
p<0.001). TAG/HDL ratio a measure of small dense LDL is positively correlated
with LDL in both groups (r=0.881 and 0.912) with p value<0.001 for both.
CONCLUSION: Correlation among Glycemic control, Insulin resistance, Thyroid
hormones, divalent cations and dyslipidemia depict differential characteristics
in obese and non-obese type2 diabetes with Thyroid comorbidity.
PMID- 28701286
TI - Association of chronic hepatitis B infection with metabolic syndrome and its
components: Meta-analysis of observational studies.
AB - INTRODUCTION: Observational studies evaluating the association between chronic
hepatitis B (CHB) and risk of metabolic syndrome (MetS) have yielded inconclusive
results. OBJECTIVE: The current meta-analysis was conducted to identify whether
CHB infection plays a role in the risk of MetS and its components. METHODS: The
electronic search of MEDLINE, PubMed Central, and EMBASE databases was
systematically performed from their inception until February 2017 to identify all
eligible studies. The most adjusted risk estimates and their corresponding 95%
confidence intervals (CIs) for the associations of chronic hepatitis B with MetS
and its components were collected and analyzed. RESULTS: A total of 13 studies,
with a total sample size of 138,994,999 subjects and 35,481,231 individuals with
MetS were included in this Meta-analysis. The results of pooled analysis revealed
that CHB infection is related to reduced risk of MetS (OR=0.83, 95%CI=0.71-0.79,
random effects), with evidence of significant heterogeneity (I2=89%, P<0.001).
This association was an age, gender, and ethnicity-dependent relationship.
Moreover, CHB was associated with reduced risk of elevated blood pressure,
reduced HDL-cholesterol, increased fasting glucose, and, most strongly with
increased triglycerides in some subgroups. The sensitivity analyses confirmed the
stability of the results. CONCLUSIONS: This meta-analysis suggests that CHB is
associated with decreased risk of MetS and some of its single components.
PMID- 28701287
TI - Effects of sex, pregnancy and season on insulin secretion and carbohydrate
metabolism in horses.
AB - In pregnant mares, peripheral insulin antagonism channels glucose preferentially
to the foetus. On the other hand, horses reduce their metabolic activity in
winter. Taking these aspects of equine pregnancy and metabolism together, we
hypothesized that glucose clearance from blood and the insulin response to
glucose do not only change throughout gestation but also with season. To test
this hypothesis, the glucose and insulin response to an oral glucose test and
relative insulin release were analysed in pregnant mares (n=12) and in geldings
(n=10) as controls. Animals were tested in June, September, December, and in
March (geldings) and on day 320 of gestation (mares). Furthermore, the 6 mares
foaling early and 6 foaling later in the year were compared. In mares and
geldings, plasma glucose concentration increased after glucose feeding (p<0.001).
The increase was more pronounced in mares (p<0.05) and increased from June to
December in mares (p<0.001) but not geldings (month x group p<0.05). This
indicates constant glucose clearance in geldings but reduced clearance in
pregnant mares. A partial insulin resistance is thus induced by pregnancy
independent from season. Insulin release increased after glucose feeding
(p<0.001) similarly in geldings and mares. The insulin response to glucose and
relative insuslin release increased from June to December (p<0.001) indicating
seasonal changes in beta-cell sensitivity. Glucose and insulin concentration did
not differ between early and late foaling mares. In conclusion, in horses, beta
cell sensitivity to glucose is affected by season while insulin sensitivity
during pregnancy decreases independent from season.
PMID- 28701288
TI - Isoflurane minimum alveolar concentration sparing effects of fentanyl in the dog.
AB - OBJECTIVE: To characterize the isoflurane-sparing effects of a high and a low
dose of fentanyl in dogs, and its effects on mean arterial pressure (MAP) and
heart rate (HR). STUDY DESIGN: Prospective, randomized crossover trial. ANIMALS:
Eight healthy male Beagle dogs weighing 12.1 +/- 1.6 kg [mean +/- standard
deviation (SD)] and approximate age 1 year. METHODS: Dogs were anesthetized using
isoflurane and minimum alveolar concentration (MAC) was determined in duplicate
by the bracketing method using an electrical stimulus on the tarsus. Animals were
administered fentanyl: low dose (33 MUg kg-1 loading dose, 0.2 MUg kg-1 minute-1)
or high dose (102 MUg kg-1 loading dose, 0.8 MUg kg-1 minute-1) and MAC was re
determined (MACISO-F). Blood was collected for analysis of plasma fentanyl
concentrations before administration and after MACISO-F determination. All values
are presented as mean +/- SD. RESULTS: Isoflurane MAC (MACISO) was 1.30 +/- 0.23%
in the low dose treatment, which significantly decreased to 0.75 +/- 0.22%
(average MAC reduction 42.3 +/- 9.4%). MACISO was 1.30 +/- 0.18% in the high dose
treatment, which significantly decreased to 0.30 +/- 0.11% (average MAC reduction
76.9 +/- 7.4%). Mean fentanyl plasma concentrations were 6.2 and 29.5 ng mL-1 for
low and high dose treatments, respectively. MAP increased significantly only in
the high dose treatment (from 81 +/- 8 to 92 +/- 9 mmHg). HR decreased
significantly in both treatments from 108 +/- 25 to 61 +/- 14 beats minute-1 with
the low dose and from 95 +/- 14 to 42 +/- 4 beats minute-1 with the high dose.
CONCLUSIONS AND CLINICAL RELEVANCE: Fentanyl administration resulted in a dose
dependent isoflurane MAC-sparing effect with bradycardia at both doses and an
increase in MAP only at high dose. Further evaluation is needed to determine the
effects of fentanyl on the overall cardiovascular function.
PMID- 28701289
TI - Chronic PM2.5 exposure and risk of infant bronchiolitis and otitis media clinical
encounters.
AB - Chronic particulate matter less than 2.5MUm in diameter (PM2.5) exposure can
leave infants more susceptible to illness. Our objective is to estimate
associations of the chronic PM2.5 exposure with infant bronchiolitis and otitis
media (OM) clinical encounters. We obtained all first time bronchiolitis
(n=18,029) and OM (n=40,042) clinical encounters among children less than 12 and
36 months of age, respectively, diagnosed from 2001 to 2009 and two controls per
case matched on birthdate and gestational age from the Pregnancy to Early Life
Longitudinal data linkage system in Massachusetts. We applied conditional
logistic regression to estimate odds ratios (OR) and confidence intervals (CI)
per 2-MUg/m3 increase in lifetime average satellite based PM2.5 exposure. Effect
modification was assessed by age, gestational age, frequency of clinical
encounter, and income. We examined associations between residential distance to
roadways, traffic density, and infant bronchiolitis and OM risk. PM2.5 was not
associated with infant bronchiolitis (OR=1.02, 95% CI=1.00, 1.04) and inversely
associated with OM (OR=0.97, 95% CI=0.95, 0.99). There was no evidence of effect
modification. Compared to infants living near low traffic density, infants
residing in high traffic density had elevated risk of bronchiolitis (OR=1.23, 95%
CI=1.14, 1.31) but not OM (OR=0.98, 95% CI=0.93, 1.02) clinical encounter. We did
not find strong evidence to support an association between early-life long-term
PM2.5 exposure and infant bronchiolitis or OM. Bronchiolitis risk was increased
among infants living near high traffic density.
PMID- 28701290
TI - Using New and Emerging Technologies to Identify and Respond to Suicidality Among
Help-Seeking Young People: A Cross-Sectional Study.
AB - BACKGROUND: Suicidal thoughts are common among young people presenting to face-to
face and online mental health services. The early detection and rapid response to
these suicidal thoughts and other suicidal behaviors is a priority for suicide
prevention and early intervention efforts internationally. Establishing how best
to use new and emerging technologies to facilitate person-centered systematic
assessment and early intervention for suicidality is crucial to these efforts.
OBJECTIVE: The aim of this study was to examine the use of a suicidality
escalation protocol to respond to suicidality among help-seeking young people.
METHODS: A total of 232 young people in the age range of 16-25 years were
recruited from either a primary mental health care service or online in the
community. Each young person used the Synergy Online System and completed an
initial clinical assessment online before their face-to-face or online clinical
appointment. A suicidality escalation protocol was used to identify and respond
to current and previous suicidal thoughts and behaviors. RESULTS: A total of 153
young people (66%, 153/232) reported some degree of suicidality and were provided
with a real-time alert online. Further levels of escalation (email or phone
contact and clinical review) were initiated for the 35 young people (15%, 35/232)
reporting high suicidality. Higher levels of psychological distress (P<.001) and
a current alcohol or substance use problem (P=.02) predicted any level of
suicidality compared with no suicidality. Furthermore, predictors of high
suicidality compared with low suicidality were higher levels of psychological
distress (P=.01), psychosis-like symptoms in the last 12 months (P=.01), a
previous mental health problem (P=.01), and a history of suicide planning or
attempts (P=.001). CONCLUSIONS: This study demonstrates the use of new and
emerging technologies to facilitate the systematic assessment and detection of
help-seeking young people presenting with suicidality. This protocol empowered
the young person by suggesting pathways to care that were based on their current
needs. The protocol also enabled an appropriate and timely response from service
providers for young people reporting high suicidality that was associated with
additional comorbid issues, including psychosis-like symptoms, and a history of
suicide plans and attempts.
PMID- 28701291
TI - Patterns of User Engagement With the Mobile App, Manage My Pain: Results of a
Data Mining Investigation.
AB - BACKGROUND: Pain is one of the most prevalent health-related concerns and is
among the top 3 most common reasons for seeking medical help. Scientific
publications of data collected from pain tracking and monitoring apps are
important to help consumers and healthcare professionals select the right app for
their use. OBJECTIVE: The main objectives of this paper were to (1) discover user
engagement patterns of the pain management app, Manage My Pain, using data mining
methods; and (2) identify the association between several attributes
characterizing individual users and their levels of engagement. METHODS: User
engagement was defined by 2 key features of the app: longevity (number of days
between the first and last pain record) and number of records. Users were divided
into 5 user engagement clusters employing the k-means clustering algorithm. Each
cluster was characterized by 6 attributes: gender, age, number of pain
conditions, number of medications, pain severity, and opioid use. Z tests and chi
square tests were used for analyzing categorical attributes. Effects of gender
and cluster on numerical attributes were analyzed using 2-way analysis of
variances (ANOVAs) followed up by pairwise comparisons using Tukey honest
significant difference (HSD). RESULTS: The clustering process produced 5 clusters
representing different levels of user engagement. The proportion of males and
females was significantly different in 4 of the 5 clusters (all P <=.03). The
proportion of males was higher than females in users with relatively high
longevity. Mean ages of users in 2 clusters with high longevity were higher than
users from other 3 clusters (all P <.001). Overall, males were significantly
older than females (P <.001). Across clusters, females reported more pain
conditions than males (all P <.001). Users from highly engaged clusters reported
taking more medication than less engaged users (all P <.001). Females reported
taking a greater number of medications than males (P =.04). In 4 of 5 clusters,
the percentage of males taking an opioid was significantly greater (all P <=.05)
than that of females. The proportion of males with mild pain was significantly
higher than that of females in 3 clusters (all P <=.008). CONCLUSIONS: Although
most users of the app reported being female, male users were more likely to be
highly engaged in the app. Users in the most engaged clusters self-reported a
higher number of pain conditions, a higher number of current medications, and a
higher incidence of opioid usage. The high engagement by males in these clusters
does not appear to be driven by pain severity which may, in part, be the case for
females. Use of a mobile pain app may be relatively more attractive to highly
engaged males than highly-engaged females, and to those with relatively more
complex chronic pain problems.
PMID- 28701292
TI - Short Text Messages to Encourage Adherence to Medication and Follow-up for People
With Psychosis (Mobile.Net): Randomized Controlled Trial in Finland.
AB - BACKGROUND: A text messaging service (short message service [SMS]) has the
potential to target large groups of people with long-term illnesses such as
serious mental disorders, who may have difficulty with treatment adherence.
Robust research on the impact of mobile technology interventions for these
patients remains scarce. OBJECTIVE: The main objective of our study was to
investigate the impact of individually tailored short text messages on the rate
of psychiatric hospital readmissions, health care service use, and clinical
outcomes. In addition, we analyzed treatment costs. METHODS: Between September
2011 and November 2012, we randomly assigned 1139 people to a tailored text
message intervention (n=569) or usual care (n=570). Participants received
semiautomated text messages for up to 12 months or usual care. The primary
outcome, based on routinely collected health register data, was patient
readmission into a psychiatric hospital during a 12-month follow-up period.
Secondary outcomes were related to other service use, coercion, medication,
adverse events, satisfaction, social functioning, quality of life, and economic
factors (cost analysis). RESULTS: There was 98.24% (1119/1139) follow-up at 12
months. Tailored mobile telephone text messages did not reduce the rate of
hospital admissions (242/563, 43.0% of the SMS group vs 216/556, 38.8% of the
control group; relative risk 1.11; 95% CI 0.92-1.33; P=.28), time between
hospitalizations (mean difference 7.0 days 95% CI -8.0 to 24.0; P=.37), time
spent in a psychiatric hospital during the year (mean difference 2.0 days 95% CI
2.0 to 7.0; P=.35), or other service outcomes. People who received text messages
were less disabled, based on Global Assessment Scale scores at the time of their
readmission, than those who did not receive text messages (odds ratio 0.68; 95%
CI 0.47-0.97; P=.04). The costs of treatment were higher for people in the SMS
group than in the control group (mean ?10,103 vs ?9210, respectively, P<.001).
CONCLUSIONS: High-grade routinely collected data can provide clear outcomes for
pragmatic randomized trials. SMS messaging tailored with the input of each
individual patient did not decrease the rate of psychiatric hospital visits after
the 12 months of follow-up. Although there may have been other, more subtle
effects, the results of these were not evident in outcomes of agreed importance
to clinicians, policymakers, and patients and their families. TRIAL REGISTRATION:
International Standard Randomized Controlled Trial Number (ISRCTN): 27704027;
http://www.isrctn.com/ISRCTN27704027 (Archived by WebCite at
http://www.webcitation.org/6rVzZrbuz).
PMID- 28701293
TI - Online Reviews as Health Data: Examining the Association Between Availability of
Health Care Services and Patient Star Ratings Exemplified by the Yelp Academic
Dataset.
AB - BACKGROUND: There have been public health interventions that aim to reduce
barriers to health care access by extending opening hours of health care
facilities. However, the impact of opening hours from the patient's perspective
is not well understood. OBJECTIVE: This study aims to investigate the
relationship between temporal accessibility of health care services and how
patients rate the providers on Yelp, an online review website that is popular in
the United States. Using crowdsourced open Internet data, such as Yelp, can help
circumvent the traditional survey method. METHODS: From Yelp's limited academic
dataset, this study examined the pattern of visits to health care providers and
performed a secondary analysis to examine the association between patient rating
(measured by Yelp's rating) and temporal accessibility of health care services
(measured by opening hours) using ordinal logistic regression models. Other
covariates included were whether an appointment was required, the type of health
care service, the region of the health care service provider, the number of
reviews the health care service provider received in the past, the number of
nearby competitors, the mean rating of competitors, and the standard deviation of
competitors' ratings. RESULTS: From the 2085 health care service providers
identified, opening hours during certain periods, the type of health care
service, and the variability of competitors' ratings showed an association with
patient rating. Most of the visits to health care service providers took place
between normal working hours (9 AM-5 PM) from Sunday to Thursday, and the least
on Saturday. A model fitted to the entire sample showed that increasing hours
during normal working hours on Monday (OR 0.926, 95% CI 0.880-0.973, P=0.03),
Saturday (OR 0.897, 95% CI 0.860-0.935, P<0.001), Sunday (OR 0.904, 95% CI 0.841
0.970, P=0.005), and outside normal working hours on Friday (OR 0.872, 95% CI
0.760-0.998, P=0.048) was associated with receiving lower ratings. But increasing
hours during outside normal working hours on Sunday was associated with receiving
higher ratings (OR 1.400, 95% CI 1.036-1.924, P=0.03). There were also observed
differences in patient ratings among the health care services types, but not
geographically or by appointment requirement. CONCLUSIONS: This study shows that
public health interventions, especially those involving opening hours, could use
crowdsourced open Internet data to enhance the evidence base for decision making
and evaluation in the future. This study illustrates one example of how Yelp data
could be used to understand patient experiences with health care services, making
a case for future research for exploring online reviews as a health dataset.
PMID- 28701294
TI - Self-Directed Telehealth Parent-Mediated Intervention for Children With Autism
Spectrum Disorder: Examination of the Potential Reach and Utilization in
Community Settings.
AB - BACKGROUND: There is a significant need for strategies to increase access to
evidence-based interventions for children with autism spectrum disorder (ASD).
One novel approach is to train parents to use evidence-based interventions for
their child with ASD via telehealth. Pilot work examining the efficacy of one
such program, ImPACT Online, demonstrated a high rate of parent program
engagement, low attrition, and associated gains in parent learning and child
social communication. OBJECTIVE: The objective of this study was to conduct an
open trial of ImPACT Online to better understand its dissemination potential.
METHODS: We examined the reach and representativeness of families who registered
(n=36) compared to families who were referred (n=139) to the open trial for one
referral site. We then compared the demographics of all families who enrolled in
the open trial (n=112) to families who enrolled in one of two controlled trials
of the same program (n=50). We also examined metrics of program engagement for
the open and controlled trials, the relationship between program engagement and
changes in parents' intervention knowledge, and program evaluation for the
participants in the open trial. RESULTS: In total, 25.8% (36/139) of the parents
who were given information about the program at their child's diagnostic feedback
session registered with the program. The parents who enrolled in the open (OT)
and controlled trials (CT), respectively, were similar in gender (OT: 84.8%
(95/112); CT: 88% (44/50), female), marital status (OT: 80.4% (90/112) ; CT:
69.6% (32/46), married), education (OT: 58.0% (65/112); CT: 54.0% (27/50),
college degree or higher), and employment status (OT: 58.0% (65/112); CT: 65.3%
(32/49), employed outside the home). The child participants were similar in terms
of gender (OT: 83.0% (93/112); CT: 76.0% (38/50), male) and race and ethnicity
(OT: 38.4% (43/112); CT: 24.0% (12/50), minority). However, the mean
chronological age of the child participants in the open trial group was
significantly higher (Mean=60.0 months) than in the controlled trial group
(Mean=43.0 months), with t160=5.22, P<.001. Parents in the open trial engaged
with the program at a significantly lower rate than the controlled trial,
F3,81=21.14, P<.001. Program engagement was significantly associated with gains
in parent intervention knowledge across both the groups, beta=.41, t=2.43, P=.02.
Participants in the open access trial evaluated the program highly, but several
barriers were noted. CONCLUSIONS: These data suggest that additional strategies
may need to be developed to support families in using telehealth-based parent
mediated intervention in community settings.
PMID- 28701295
TI - "Diminishing returns" in the scaling of leaf area vs. dry mass in Wuyi Mountain
bamboos, Southeast China.
AB - PREMISE OF STUDY: Leaf area and dry mass are crucial for plant metabolic
performance. The "diminishing returns" hypothesis predicts that leaf area will
scale less than one with respect to leaf dry mass, indicating that the cost of
light interception increases with leaf area. However, it remains unclear whether
and how this scaling relationship varies among species growing in different
environments. METHODS: More than 2000 measurements from five bamboo species
adapted to high and low light and growing at different elevations in Wuyi
Mountains, Southeast China, were used to explore how the leaf area vs. dry mass
scaling relationship was affected by light and elevation. KEY RESULTS: The data
indicate that (1) the normalization constants for leaf area vs. dry mass were
positively but not significantly correlated with increasing leaf size and that
(2) the scaling exponents remained numerically invariant among all five bamboo
species, with a common slope of 0.85. Standardized major axis (SMA) analyses and
comparisons of 95% confidence intervals also showed that the numerical values of
the scaling exponents did not differ regardless of elevation and were similar
between shaded and unshaded adapted species, whereas the numerical values of the
normalization constants increased with decreasing light. CONCLUSIONS: The data
collected for all five bamboo species are consistent with the "diminishing
returns" hypothesis, i.e., the scaling exponents governing the leaf area vs. dry
mass scaling relationship are less than one within and across species and are
insensitive to light conditions or elevation.
PMID- 28701296
TI - Herbarium specimens as exaptations: New uses for old collections.
PMID- 28701297
TI - Genomic analysis of an infant with intractable diarrhea and dilated
cardiomyopathy.
AB - We describe a case of an infant presenting with intractable diarrhea who
subsequently developed dilated cardiomyopathy, for whom a diagnosis was not
initially achieved despite extensive clinical testing, including panel-based
genetic testing. Research-based whole-genome sequences of the proband and both
parents were analyzed by the SAVANNA pipeline, a variant prioritization strategy
integrating features of variants, genes, and phenotypes, which was implemented
using publicly available tools. Although the intestinal morphological
abnormalities characteristic of congenital tufting enteropathy (CTE) were not
observed in the initial clinical gastrointestinal tract biopsies of the proband,
an intronic variant, EPCAM c.556-14A>G, previously identified as pathogenic for
CTE, was found in the homozygous state. A newborn cousin of the proband also
presenting with intractable diarrhea was found to carry the same homozygous EPCAM
variant, and clinical testing revealed intestinal tufting and loss of EPCAM
staining. This variant, however, was considered nonexplanatory for the proband's
dilated cardiomyopathy, which could be a sequela of the child's condition and/or
related to other genetic variants, which include de novo mutations in the genes
NEDD4L and GSK3A and a maternally inherited SCN5A variant. This study illustrates
three ways in which genomic sequencing can aid in the diagnosis of clinically
challenging patients: differential diagnosis despite atypical clinical
presentation, distinguishing the possibilities of a syndromic condition versus
multiple conditions, and generating hypotheses for novel contributory genes.
PMID- 28701298
TI - Carotid stenting for unilateral stenosis can increase contralateral hemispheric
cerebral blood flow.
AB - BACKGROUND: The revascularization of carotid stenosis can increase ipsilateral
cerebral blood flow (CBF). Occasionally, elevated CBF is also evident on the
contralateral side, but this phenomenon is poorly understood. OBJECTIVE: To
analyze retrospectively the relationship between a contralateral CBF increase and
several clinical and radiologic features. MATERIALS AND METHODS: We
retrospectively analyzed 40 patients with unilateral cervical carotid stenosis
treated by carotid artery stenting (CAS). Using 123I-iodamphetamine single-photon
emission computed tomography (SPECT); we compared pre- and postoperative
hemispheric CBF on both sides. We investigated the influence of the following
five factors on the increase of the contralateral hemispheric CBF: stenosis grade
(>=50% or <50%, according to the North American Symptomatic Carotid
Endarterectomy Trial criteria); age; the presence of anterior and posterior
communicating arteries; postoperative hyperperfusion on the stenotic side; and
the presence of cerebral steal phenomenon during preoperative acetazolamide
challenge SPECT. RESULTS: Following unilateral CAS, mean hemispheric CBF
increased significantly on both sides: from 33.4+/-5.6 (mean +/- SD) to 38.7+/
7.8 mL/min on the operated side (paired t test, p<0.001) and f35.4+/-5.4 to
39.2+/-7.2 mL/min on the contralateral side (p<0.001). In a general linear model,
stenosis grade (>=50%) alone was significantly correlated with the increase of
the CBF on the contralateral side (p=0.03). CONCLUSION: Revascularization by CAS
for unilateral carotid stenosis can increase hemispheric CBF on both sides.
Increase of the contralateral CBF is correlated with stenosis grade (>=50%).
PMID- 28701299
TI - Modeled changes in US sodium intake from reducing sodium concentrations of
commercially processed and prepared foods to meet voluntary standards established
in North America: NHANES.
AB - Background: Approximately 2 in 3 US adults have prehypertension or hypertension
that increases their risk of cardiovascular disease. Reducing sodium intake can
decrease blood pressure and prevent hypertension. Approximately 9 in 10 Americans
consume excess sodium (>=2300 mg/d). Voluntary sodium standards for commercially
processed and prepared foods were established in North America, but their impact
on sodium intake is unclear.Objective: We modelled the potential impact on US
sodium intake of applying voluntary sodium standards for foods.Design: We used
NHANES 2007-2010 data for 17,933 participants aged >=1 y to model predicted US
daily mean sodium intake and the prevalence of excess sodium intake with the use
of the standards of the New York City's National Salt Reduction Initiative (NSRI)
and Health Canada for commercially processed and prepared foods. The Food and
Nutrient Database for Dietary Studies food codes corresponding to foods reported
by NHANES participants were matched to NSRI and Health Canada food categories,
and the published sales-weighted mean percent reductions were applied.Results:
The US population aged >=1 y could have reduced their usual daily mean sodium
intake of 3417 mg by 698 mg (95% CI: 683, 714 mg) by applying NSRI 2014 targets
and by 615 mg (95% CI: 597, 634 mg) by applying Health Canada's 2016 benchmarks.
Significant reductions could have occurred, regardless of age, sex,
race/ethnicity, income, education, or hypertension status, up to a mean reduction
in sodium intake of 850 mg/d in men aged >=19 y by applying NSRI targets. The
proportion of adults aged >=19 y who consume >=2300 mg/d would decline from 88%
(95% CI: 86%, 91%) to 71% (95% CI: 68%, 73%) by applying NSRI targets and to 74%
(95% CI: 71%, 76%) by applying Health Canada benchmarks.Conclusion: If
established sodium standards are applied to commercially processed and prepared
foods, a significant reduction of US sodium intake could occur.
PMID- 28701300
TI - Duodenal and ileal glucose infusions differentially alter gastrointestinal
peptides, appetite response, and food intake: a tube feeding study.
AB - Background: Activation of the ileal brake through the delivery of nutrients into
the distal small intestine to promote satiety and suppress food intake provides a
new target for weight loss. Evidence is limited, with support from naso-ileal
lipid infusion studies.Objective: The objective of the study was to investigate
whether glucose infused into the duodenum and ileum differentially alters
appetite response, food intake, and secretion of satiety-related gastrointestinal
peptides.Design: Fourteen healthy male participants were randomly assigned to a
blinded 4-treatment crossover, with each treatment of single-day duration. On the
day before the intervention (day 0), a 380-cm multilumen tube (1.75-mm diameter)
with independent port access to the duodenum and ileum was inserted, and position
was confirmed by X-ray. Subsequently (days 1-4), a standardized breakfast meal
was followed midmorning by a 90-min infusion of isotonic glucose (15 g, 235 kJ)
or saline to the duodenum or ileum. Appetite ratings were assessed with the use
of visual analog scales (VASs), blood samples collected, and ad libitum energy
intake (EI) measured at lunch, afternoon snack, and dinner.Results: Thirteen
participants completed the 4 infusion days. There was a significant effect of
nutrient infused and site (treatment * time, P < 0.05) such that glucose-to-ileum
altered VAS-rated fullness, satisfaction, and thoughts of food compared with
saline-to-ileum (Tukey's post hoc, P < 0.05); decreased ad libitum EI at lunch
compared with glucose-to-duodenum [-22%, -988 +/- 379 kJ (mean +/- SEM), Tukey's
post hoc, P < 0.05]; and increased glucagon-like peptide-1 (GLP-1) and peptide YY
(PYY) compared with all other treatments (Tukey's post hoc, P <
0.05).Conclusions: Macronutrient delivery to the proximal and distal small
intestine elicits different outcomes. Glucose infusion to the ileum increased GLP
1 and PYY secretion, suppressed aspects of VAS-rated appetite, and decreased ad
libitum EI at a subsequent meal. Although glucose to the duodenum also suppressed
appetite ratings, eating behavior was not altered. This trial was registered at
www.anzctr.org.au as ACTRN12612000429853.
PMID- 28701301
TI - Modulation of receptor signaling by metabolic environment.
PMID- 28701302
TI - Enduring challenges in estimating the effect of the food environment on obesity.
PMID- 28701304
TI - HIF1A up-regulates the ADORA2B receptor on alternatively activated macrophages
and contributes to pulmonary fibrosis.
AB - Idiopathic pulmonary fibrosis (IPF) is a deadly chronic lung disease.
Extracellular accumulation of adenosine and subsequent activation of the ADORA2B
receptor play important roles in regulating inflammation and fibrosis in IPF.
Additionally, alternatively activated macrophages (AAMs) expressing ADORA2B have
been implicated in mediating adenosine's effects in IPF. Although hypoxic
conditions are present in IPF, hypoxia's role as a direct modulator of macrophage
phenotype and identification of factors that regulate ADORA2B expression on AAMs
in IPF is not well understood. In this study, an experimental mouse model of
pulmonary fibrosis and lung samples from patients with IPF were used to examine
the effects and interactions of macrophage differentiation and hypoxia on
fibrosis. We demonstrate that hypoxia-inducible factor 1-alpha (HIF1A) inhibition
in late stages of bleomycin-induced injury attenuates pulmonary fibrosis in
association, with reductions in ADORA2B expression in AAMs. Additionally, ADORA2B
deletion or pharmacological antagonism along with HIF1A inhibition disrupts AAM
differentiation and subsequent IL-6 production in cultured macrophages. These
findings suggest that hypoxia, through HIF1A, contributes to the development and
progression of pulmonary fibrosis through its regulation of ADORA2B expression on
AAMs, cell differentiation, and production of profibrotic mediators. These
studies support a potential role for HIF1A or ADORA2B antagonists in the
treatment of IPF.-Philip, K., Mills, T. W., Davies, J., Chen, N.-Y., Karmouty
Quintana, H., Luo, F., Molina, J. G., Amione-Guerra, J., Sinha, N., Guha, A.,
Eltzschig, H. K., Blackburn, M. R. HIF1A up-regulates the ADORA2B receptor on
alternatively activated macrophages and contributes to pulmonary fibrosis.
PMID- 28701303
TI - Endothelial cell SHP-2 negatively regulates neutrophil adhesion and promotes
transmigration by enhancing ICAM-1-VE-cadherin interaction.
AB - Intercellular adhesion molecule-1 (ICAM-1) mediates the firm adhesion of
leukocytes to endothelial cells and initiates subsequent signaling that promotes
their transendothelial migration (TEM). Vascular endothelial (VE)-cadherin plays
a critical role in endothelial cell-cell adhesion, thereby controlling
endothelial permeability and leukocyte transmigration. This study aimed to
determine the molecular signaling events that originate from the ICAM-1-mediated
firm adhesion of neutrophils that regulate VE-cadherin's role as a negative
regulator of leukocyte transmigration. We observed that ICAM-1 interacts with Src
homology domain 2-containing phosphatase-2 (SHP-2), and SHP-2 down-regulation via
silencing of small interfering RNA in endothelial cells enhanced neutrophil
adhesion to endothelial cells but inhibited neutrophil transmigration. We also
found that VE-cadherin associated with the ICAM-1-SHP-2 complex. Moreover,
whereas the activation of ICAM-1 leads to VE-cadherin dissociation from ICAM-1
and VE-cadherin association with actin, SHP-2 down-regulation prevented ICAM-1-VE
cadherin association and promoted VE-cadherin-actin association. Furthermore, SHP
2 down-regulation in vivo promoted LPS-induced neutrophil recruitment in mouse
lung but delayed neutrophil extravasation. These results suggest that SHP-2-via
association with ICAM-1-mediates ICAM-1-induced Src activation and modulates VE
cadherin switching association with ICAM-1 or actin, thereby negatively
regulating neutrophil adhesion to endothelial cells and enhancing their TEM.-Yan,
M., Zhang, X., Chen, A., Gu, W., Liu, J., Ren, X., Zhang, J., Wu, X., Place, A.
T., Minshall, R. D., Liu, G. Endothelial cell SHP-2 negatively regulates
neutrophil adhesion and promotes transmigration by enhancing ICAM-1-VE-cadherin
interaction.
PMID- 28701305
TI - Redox and Activation of Protein Kinase A Dysregulates Calcium Homeostasis in
Pulmonary Vein Cardiomyocytes of Chronic Kidney Disease.
AB - BACKGROUND: Chronic kidney disease (CKD) increases the occurrence of atrial
fibrillation and pulmonary vein (PV) arrhythmogenesis. Calcium dysregulation and
reactive oxygen species (ROS) enhance PV arrhythmogenic activity. The purposes of
this study were to investigate whether CKD modulates PV electrical activity
through dysregulation of calcium homeostasis and ROS. METHODS AND RESULTS:
Biochemical and electrocardiographic studies were conducted in rabbits with and
without CKD (induced by 150 mg/kg per day neomycin sulfate and 500 mg/kg per day
cefazolin). Confocal microscopy with fluorescence and a whole-cell patch clamp
were applied to study calcium homeostasis and electrical activities in control
and CKD isolated single PV cardiomyocytes with or without treatment with H89 (1
MUmol/L, a protein kinase A inhibitor) and MPG (N-[2-mercaptopropionyl]glycine;
100 MUmol/L, a ROS scavenger). The ROS in mitochondria and cytosol were evaluated
via intracellular dye fluorescence and lipid peroxidation. CKD rabbits had
excessive atrial premature captures over those of control rabbits. Compared with
the control, CKD PV cardiomyocytes had a faster beating rate and larger calcium
transient amplitudes, sarcoplasmic reticulum calcium contents, sodium/calcium
exchanger currents, and late sodium currents but smaller L-type calcium current
densities. CKD PV cardiomyocytes had a higher frequency and longer duration of
calcium sparks and more ROS in the mitochondria and cytosol than did controls.
Moreover, H89 suppressed all calcium sparks in CKD PV cardiomyocytes, and H89-
and MPG-treated CKD PV cardiomyocytes had similar calcium transients compared
with control PV cardiomyocytes. CONCLUSIONS: CKD increases PV arrhythmogenesis
with enhanced calcium-handling abnormalities through activation of protein kinase
A and ROS.
PMID- 28701306
TI - Geographic Variations in Cardiovascular Disease Mortality Among Asian American
Subgroups, 2003-2011.
AB - BACKGROUND: There are well-documented geographical differences in cardiovascular
disease (CVD) mortality for non-Hispanic whites. However, it remains unknown
whether similar geographical variation in CVD mortality exists for Asian American
subgroups. This study aims to examine geographical differences in CVD mortality
among Asian American subgroups living in the United States and whether they are
consistent with geographical differences observed among non-Hispanic whites.
METHODS AND RESULTS: Using US death records from 2003 to 2011 (n=3 897 040 CVD
deaths), age-adjusted CVD mortality rates per 100 000 population and age-adjusted
mortality rate ratios were calculated for the 6 largest Asian American subgroups
(Asian Indian, Chinese, Filipino, Japanese, Korean, and Vietnamese) and compared
with non-Hispanic whites. There were consistently lower mortality rates for all
Asian American subgroups compared with non-Hispanic whites across divisions for
CVD mortality and ischemic heart disease mortality. However, cerebrovascular
disease mortality demonstrated substantial geographical differences by Asian
American subgroup. There were a number of regional divisions where certain Asian
American subgroups (Filipino and Japanese men, Korean and Vietnamese men and
women) possessed no mortality advantage compared with non-Hispanic whites. The
most striking geographical variation was with Filipino men (age-adjusted
mortality rate ratio=1.18; 95% CI, 1.14-1.24) and Japanese men (age-adjusted
mortality rate ratio=1.05; 95% CI: 1.00-1.11) in the Pacific division who had
significantly higher cerebrovascular mortality than non-Hispanic whites.
CONCLUSIONS: There was substantial geographical variation in Asian American
subgroup mortality for cerebrovascular disease when compared with non-Hispanic
whites. It deserves increased attention to prioritize prevention and treatment in
the Pacific division where approximately 80% of Filipinos CVD deaths and 90% of
Japanese CVD deaths occur in the United States.
PMID- 28701307
TI - Increasing National Institutes of Health Funding for Cardiac Arrest Research.
PMID- 28701308
TI - National Institutes of Health-Funded Cardiac Arrest Research: A 10-Year Trend
Analysis.
AB - BACKGROUND: Cardiac arrest (CA) is a leading cause of death in the United States,
claiming over 450 000 lives annually. Improving survival depends on the ability
to conduct CA research and on the translation and implementation of research
findings into practice. Our objective was to provide a descriptive analysis of
annual National Institutes of Health (NIH) funding for CA research over the past
decade. METHOD AND RESULTS: A search within NIH RePORTER for the years 2007 to
2016 was performed using the terms: "cardiac arrest" or "cardiopulmonary
resuscitation" or "heart arrest" or "circulatory arrest" or "pulseless electrical
activity" or "ventricular fibrillation" or "resuscitation." Grants were reviewed
and categorized as CA research (yes/no) using predefined criteria. The annual NIH
funding for CA research, number of individual grants, and principal investigators
were tabulated. The total NIH investment in CA research for 2015 was calculated
and compared to those for other leading causes of death within the United States.
Interrater reliability among 3 independent reviewers for fiscal year 2015 was
assessed using Fleiss kappa. The search yielded 2763 NIH-funded grants, of which
745 (27.0%) were classified as CA research (kappa=0.86 [95%CI 0.80-0.93]). Total
inflation-adjusted NIH funding for CA research was $35.4 million in 2007, peaked
at $76.7 million in 2010, and has decreased to $28.5 million in 2016. Per annual
death, NIH invests ~$2200 for stroke, ~$2100 for heart disease, and ~$91 for CA.
CONCLUSIONS: This analysis demonstrates that the annual NIH investment in CA
research is low relative to other leading causes of death in the United States
and has declined over the past decade.
PMID- 28701309
TI - ARHGAP18 Protects Against Thoracic Aortic Aneurysm Formation by Mitigating the
Synthetic and Proinflammatory Smooth Muscle Cell Phenotype.
AB - RATIONALE: Thoracic aortic aneurysm (TAA) is a potentially lethal condition,
which can affect individuals of all ages. TAA may be complicated by the sudden
onset of life-threatening dissection or rupture. The underlying mechanisms
leading to TAA formation, particularly in the nonsyndromal idiopathic group of
patients, are not well understood. Thus, identification of new genes and targets
that are involved in TAA pathogenesis are required to help prevent and reverse
the disease phenotype. OBJECTIVE: Here we explore the role of ARHGAP18, a novel
Rho GAP expressed by smooth muscle cells (SMCs), in the pathogenesis of TAA.
METHODS AND RESULTS: Using human and mouse aortic samples, we report that
ARHGAP18 levels were significantly reduced in the SMC layer of aortic aneurysms.
Arhgap18 global knockout (Arhgap18-/-) mice exhibited a highly synthetic,
proteolytic, and proinflammatory smooth muscle phenotype under basal conditions
and when challenged with angiotensin II, developed TAA with increased frequency
and severity compared with littermate controls. Chromatin immunoprecipitation
studies revealed this phenotype is partly associated with strong enrichment of
H3K4me3 and depletion of H3K27me3 at the MMP2 and TNF-alpha promoters in Arhgap18
deficient SMC. We further show that TAA formation in the Arhgap18-/- mice is
associated with loss of Akt activation. The abnormal SMC phenotype observed in
the Arhgap18-/- mice can be partially rescued by pharmacological treatment with
the mTORC1 inhibitor rapamycin, which reduces the synthetic and proinflammatory
phenotype of Arhgap18-deficient SMC. CONCLUSION: We have identified ARHGAP18 as a
novel protective gene against TAA formation and define an additional target for
the future development of treatments to limit TAA pathogenesis.
PMID- 28701310
TI - Deletion of beta1-integrin in collecting duct principal cells leads to tubular
injury and renal medullary fibrosis.
AB - The renal collecting duct (CD) contains two major cell types, intercalated (ICs)
and principal cells (PCs). A previous report showed that deletion of beta1
integrin in the entire renal CD causes defective CD morphogenesis resulting in
kidney dysfunction. However, subsequent deletion of beta1-integrin specifically
in ICs and PCs, respectively, did not cause any morphological defects in the CDs.
The discrepancy between these studies prompts us to reinvestigate the role of
beta1-integrin in CD cells, specifically in the PCs. We conditionally deleted
beta1-integrin in mouse CD PCs using a specific aquaporin-2 (AQP2) promoter Cre
LoxP system. The resulting mutant mice, beta-1f/fAQP2-Cre+, had lower body
weight, failed to thrive, and died around 8-12 wk. Their CD tubules were dilated,
and some of them contained cellular debris. Increased apoptosis and proliferation
of PCs were observed in the dilated CDs. Trichrome staining and electron
microscopy revealed the presence of peritubular and interstitial fibrosis that is
associated with increased production of extracellular matrix proteins including
collagen type IV and fibronectin, as detected by immunoblotting. Further analysis
revealed a significantly increased expression of transforming growth factor-beta
(TGF-beta)-induced protein, fibronectin, and TGF-beta receptor-1 mRNAs and
concomitantly increased phosphorylation of SMAD-2 that indicates the activation
of the TGF-beta signaling pathway. Therefore, our data reveal that normal
expression of beta1-integrin in PCs is a critical determinant of CD structural
and functional integrity and further support the previously reported critical
role of beta1-integrin in the development and/or maintenance of the CD structure
and function.
PMID- 28701311
TI - PGE2 upregulates renin through E-prostanoid receptor 1 via PKC/cAMP/CREB pathway
in M-1 cells.
AB - During the early phase of ANG II-dependent hypertension, tubular PGE2 is
increased. Renin synthesis and secretion in the collecting duct (CD) are
upregulated by ANG II, contributing to further intratubular ANG II formation.
However, what happens first and whether the triggering mechanism is independent
of tubular ANG II remain unknown. PGE2 stimulates renin synthesis in
juxtaglomerular cells via E-prostanoid (EP) receptors through the cAMP/cAMP
responsive element-binding (CREB) pathway. EP receptors are also expressed in the
CD. Here, we tested the hypothesis that renin is upregulated by PGE2 in CD cells.
The M-1 CD cell line expressed EP1, EP3, and EP4 but not EP2. Dose-response
experiments, in the presence of ANG II type 1 receptor blockade with candesartan,
demonstrated that 10-6 M PGE2 maximally increases renin mRNA (approximately 4
fold) and prorenin/renin protein levels (approximately 2-fold). This response was
prevented by micromolar doses of SC-19220 (EP1 antagonist), attenuated by the EP4
antagonist, L-161982, and exacerbated by the highly selective EP3 antagonist, L
798106 (~10-fold increase). To evaluate further the signaling pathway involved,
we used the PKC inhibitor calphostin C and transfections with PKCalpha dominant
negative. Both strategies blunted the PGE2-induced increases in cAMP levels, CREB
phosphorylation, and augmentation of renin. Knockdown of the EP1 receptor and
CREB also prevented renin upregulation. These results indicate that PGE2
increases CD renin expression through the EP1 receptor via the PKC/cAMP/CREB
pathway. Therefore, we conclude that during the early stages of ANG II-dependent
hypertension, there is augmentation of PGE2 that stimulates renin in the CD,
resulting in increased tubular ANG II formation and further stimulation of renin.
PMID- 28701312
TI - Inflammation and premature aging in advanced chronic kidney disease.
AB - Systemic inflammation in end-stage renal disease is an established risk factor
for mortality and a catalyst for other complications, which are related to a
premature aging phenotype, including muscle wasting, vascular calcification, and
other forms of premature vascular disease, depression, osteoporosis, and frailty.
Uremic inflammation is also mechanistically related to mechanisms involved in the
aging process, such as telomere shortening, mitochondrial dysfunction, and
altered nutrient sensing, which can have a direct effect on cellular and tissue
function. In addition to uremia-specific causes, such as abnormalities in the
phosphate-Klotho axis, there are remarkable similarities between the
pathophysiology of uremic inflammation and so-called "inflammaging" in the
general population. Potentially relevant, but still somewhat unexplored in this
respect, are abnormal or misplaced protein structures, as well as abnormalities
in tissue homeostasis, which evoke danger signals through damage-associated
molecular patterns, as well as the senescence-associated secretory phenotype.
Systemic inflammation, in combination with the loss of kidney function, can
impair the resilience of the body to external and internal stressors by reduced
functional and structural tissue reserves, and by impairing normal organ
crosstalk, thus providing an explanation for the greatly increased risk of
homeostatic breakdown in this population. In this review, the relationship
between uremic inflammation and a premature aging phenotype, as well as potential
causes and consequences, are discussed.
PMID- 28701313
TI - Dynamic regulation of lysine acetylation: the balance between acetyltransferase
and deacetylase activities.
AB - Reversible posttranslational modification of proteins is a critically important
process in physiological regulation in all tissues, including the kidney. Lysine
acetylation occurs in all organisms, including prokaryotes, and is regulated by a
balance between the lysine acetyltransferases (adding an acetyl group to the
epsilon-amino group of a lysine) and deacetylases (removing it). The kidney is an
organ rich with acetylated lysines, which map to >2,000 unique histone and
nonhistone proteins. However, the functional significance of these modifications
remains to be discovered. Here, we have compiled gene lists of the
acetyltransferases and deacetylases in the mammalian genomes and mapped their
mRNA expression along the renal tubule. These lists will be useful for generating
targeted approaches to test the physiological or pathophysiological significance
of lysine acetylation changes in the kidney.
PMID- 28701314
TI - Cux1 promotes cell proliferation and polycystic kidney disease progression in an
ADPKD mouse model.
AB - Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common
monogenic hereditary disorders in humans characterized by fluid-filled cysts,
primarily in the kidneys. Cux1, a cell cycle regulatory gene highly expressed
during kidney development, is elevated in the cyst-lining cells of Pkd1 mutant
mice, and in human ADPKD cells. However, forced expression of Cux1 is
insufficient to induce cystic disease in transgenic mice or to induce rapid cyst
formation after cilia disruption in the kidneys of adult mice. Here we report a
double mutant mouse model that has a conditional deletion of the Pkd1 gene in the
renal collecting ducts together with a targeted mutation in the Cux1 gene
(Pkd1CD;Cux1tm2Ejn). While kidneys isolated from newborn Pkd1CD mice exhibit
cortical and medullary cysts, kidneys isolated from newborn Pkd1CD;Cux1tm2Ejn-/-
mice did not show any cysts. Because Cux1tm2Ejn-/- are perinatal lethal, we
evaluated Pkd1CD mice that were heterozygote for the Cux1 mutation. Similar to
the newborn Pkd1CD;Cux1tm2Ejn-/- mice, newborn Pkd1CD;Cux1tm2Ejn+/- mice did not
show any cysts. Comparison of Pkd1CD and Pkd1CD;Cux1tm2Ejn+/- mice at later
stages of development showed a reduction in the severity of PKD in the
Pkd1CD;Cux1tm2Ejn+/- mice. Moreover, we observed an increase in expression of the
cyclin kinase inhibitor p27, a target of Cux1 repression, in the rescued
collecting ducts. Taken together, our results suggest that Cux1 expression in PKD
is not directly involved in cystogenesis but promotes cell proliferation required
for expansion of existing cysts, primarily by repression of p27.
PMID- 28701315
TI - Effect of endurance training and branched-chain amino acids on the signaling for
muscle protein synthesis in CKD model rats fed a low-protein diet.
AB - A low-protein diet (LPD) protects against the progression of renal injury in
patients with chronic kidney disease (CKD). However, LPD may accelerate muscle
wasting in these patients. Both exercise and branched-chain amino acids (BCAA)
are known to increase muscle protein synthesis by activating the mammalian target
of rapamycin (mTOR) pathway. The aim of this study was to investigate whether
endurance exercise and BCAA play a role for increasing muscle protein synthesis
in LPD-fed CKD (5/6 nephrectomized) rats. Both CKD and sham rats were pair-fed on
LPD or LPD fortified with a BCAA diet (BD), and approximately one-half of the
animals in each group was subjected to treadmill exercise (15 m/min, 1 h/day, 5
days/wk). After 7 wk, renal function was measured, and soleus muscles were
collected to evaluate muscle protein synthesis. Renal function did not differ
between LPD- and BD-fed CKD rats, and the treadmill exercise did not accelerate
renal damage in either group. The treadmill exercise slightly increased the
phosphorylation of p70s6 kinase, a marker of mTOR activity, in the soleus muscle
of LPD-fed CKD rats compared with the sham group. Furthermore, BCAA
supplementation of the LPD-fed, exercise-trained CKD rats restored the
phosphorylation of p70s6 kinase to the same level observed in the sham group;
however, the corresponding induced increase in muscle protein synthesis and
muscle mass was marginal. These results indicate that the combination of
treadmill exercise and BCAA stimulates cell signaling to promote muscle protein
synthesis; however, the implications of this effect for muscle growth remain to
be clarified.
PMID- 28701316
TI - Diagnostic Performance of High Sensitivity Compared with Contemporary Cardiac
Troponin I for the Diagnosis of Acute Myocardial Infarction.
AB - BACKGROUND: We examined the diagnostic performance of high-sensitivity cardiac
troponin I (hs-cTnI) vs contemporary cTnI with use of the 99th percentile alone
and with a normal electrocardiogram (ECG) to rule out acute myocardial infarction
(MI) and serial changes (deltas) to rule in MI. METHODS: We included consecutive
patients presenting to a US emergency department with serial cTnI onclinical
indication. Diagnostic performance for acute MI, including MI subtypes, and 30
day outcomes were examined. RESULTS: Among 1631 patients, MI was diagnosed in
12.9% using the contemporary cTnI assay and in 10.4% using the hs-cTnI assay. For
ruling out MI, contemporary cTnI <=99th percentile at 0, 3, and 6 h and a normal
ECG had a negative predictive value (NPV) of 99.5% (95% CI, 98.6-100) and a
sensitivity of 99.1% (95% CI, 97.4-100) for diagnostic and safety outcomes.
Serial hs-cTnI measurements <=99th percentile at 0 and 3 h and a normal ECG had
an NPV and sensitivity of 100% (95% CI, 100-100) for diagnostic and safety
outcomes. For ruling in MI, contemporary cTnI measurements had specificities of
84.4% (95% CI, 82.5-86.3) at presentation and 78.7% (95% CI, 75.4-82.0) with
serial testing at 0, 3, and 6 h, improving to 89.2% (95% CI, 87.1-91.3) by using
serial cTnI changes (delta, 0 and 6 h) >150%. hs-cTnI had specificities of 86.9%
(95% CI, 85.1-88.6) at presentation and 85.7% (95% CI, 83.5-87.9) with serial
testing at 0 and 3 h, improving to 89.3% (95% CI, 87.3-91.2) using a delta hs
cTnI (0 and 3 h) >5 ng/L. CONCLUSIONS: hs-cTnI and contemporary cTnI assays are
excellent in ruling out MI following recommendations predicated on serial testing
and the 99th percentile with a normal ECG. For ruling in MI, deltas improve the
specificity. ClinicalTrials.gov Identifier: NCT02060760.
PMID- 28701317
TI - Redefining the overlap of asthma and COPD.
AB - The term asthma-COPD overlap (ACO) has been suggested for people with chronic
airflow obstruction that has features characteristic of both asthma and chronic
obstructive pulmonary disease (COPD).1 People with clinical features of asthma
and COPD tend to have worse outcomes than those with either asthma or COPD alone,
yet their clinical management has remained unclear. UK guidelines currently do
not specifically address this issue,2,3 but the Global Initiative for Asthma
(GINA) and the Global Initiative for Chronic Obstructive Lung Disease (GOLD) have
published a consensus-based report on the diagnosis and treatment of people with
asthma, COPD and ACO.1 Although 'asthma-COPD overlap syndrome' (ACOS) was briefly
used, some thought that it gave the unhelpful impression that it referred to a
single disease entity. Here, we consider some of the challenges in managing this
heterogeneous group of patients.
PMID- 28701318
TI - ? Liraglutide for weight management.
AB - Since 1950, 25 anti-obesity drugs have been withdrawn from use across the world,
largely as a result of adverse effects.1 For several years, orlistat has been the
only drug licensed in the UK for weight management.2 In January 2017, a new
presentation of the glucagon-like peptide-1 (GLP-1) analogue liraglutide
(?Saxenda - Novo Nordisk) was launched in the UK as an adjunct to a reduced
calorie diet and increased physical activity for weight management in adults.
Here, we review the evidence for its efficacy and safety and consider its place
in managing people who are overweight or obese.
PMID- 28701319
TI - Low-carbohydrate diet induces metabolic depression: a possible mechanism to
conserve glycogen.
AB - Long-term studies have found that low-carbohydrate diets are more effective for
weight loss than calorie-restricted diets in the short term but equally or only
marginally more effective in the long term. Low-carbohydrate diets have been
linked to reduced glycogen stores and increased feelings of fatigue. We propose
that reduced physical activity in response to lowered glycogen explains the
diminishing weight loss advantage of low-carbohydrate compared with low-calorie
diets over longer time periods. We explored this possibility by feeding adult
Drosophila melanogaster a standard or a low-carbohydrate diet for 9 days and
measured changes in metabolic rate, glycogen stores, activity, and body mass. We
hypothesized that a low-carbohydrate diet would cause a reduction in glycogen
stores, which recover over time, a reduction in physical activity, and an
increase in resting metabolic rate. The low-carbohydrate diet reduced glycogen
stores, which recovered over time. Activity was unaffected by diet, but metabolic
rate was reduced, in the low-carbohydrate group. We conclude that metabolic
depression could explain the decreased effectiveness of low-carbohydrate diets
over time and recommend further investigation of long-term metabolic effects of
dietary interventions and a greater focus on physiological plasticity within the
study of human nutrition.
PMID- 28701321
TI - Pituitary adenylate cyclase-activating polypeptide drives cardiorespiratory
responses to heat stress in neonatal mice.
AB - The neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP) has
emerged as a principal and rate-limiting regulator of physiological stress
responses in adult rodents and has been implicated in sudden infant death
syndrome (SIDS). Recent studies show that PACAP plays a role in neonatal
cardiorespiratory responses to hypoxia, hypercapnia, and hypothermia, but not
hyperthermia, which is often associated with SIDS. Here we tested the hypothesis
that, consistent with a role in SIDS, PACAP is involved in regulating the
neonatal cardiorespiratory responses to severe heat. To address this, we used
head-out plethysmography and surface ECG electrodes to study the
cardiorespiratory physiology of conscious neonatal PACAP-null and wild-type mice
at ambient temperatures of 32 degrees C (baseline) and 40 degrees C (heat
stress). We also assessed body surface temperature as an indicator of cutaneous
heat loss. Our results show that wild-type neonatal mice respond to heat stress
by increasing ventilation (P = 0.007) and associated expired CO2 (P = 0.041),
heart rate (P < 0.001), and cutaneous heat loss (P < 0.001). In PACAP-null
neonates, this heat response is impaired, as indicated by a decrease in
ventilation (P = 0.04) and associated expired CO2 (P = 0.006) and a blunted
increase in heart rate (P = 0.001) and cutaneous heat loss (P = 0.0002). In
addition, heart rate variability at baseline was lower in PACAP-null neonates
than wild-type controls (P < 0.01). These results suggest that, during heat
stress, PACAP is important for neonatal cardiorespiratory responses that help
regulate body temperature. Abnormal PACAP regulation could, therefore, contribute
to neonatal disorders in which the autonomic response to stress is impaired, such
as SIDS.
PMID- 28701320
TI - Changes in microvascular density differentiate metabolic health outcomes in
monkeys with prior radiation exposure and subsequent skeletal muscle ECM
remodeling.
AB - Radiation exposure accelerates the onset of age-related diseases such as
diabetes, cardiovascular disease, and neoplasia and, thus, lends insight into in
vivo mechanisms common to these disorders. Fibrosis and extracellular matrix
(ECM) remodeling, which occur with aging and overnutrition and following
irradiation, are risk factors for development of type 2 diabetes mellitus. We
previously demonstrated an increased incidence of skeletal muscle insulin
resistance and type 2 diabetes mellitus in monkeys that had been exposed to whole
body irradiation 5-9 yr prior. We hypothesized that irradiation-induced fibrosis
alters muscle architecture, predisposing irradiated animals to insulin resistance
and overt diabetes. Rhesus macaques (Macaca mulatta, n = 7-8/group) grouped as
nonirradiated age-matched controls (Non-Rad-CTL), irradiated nondiabetic monkeys
(Rad-CTL), and irradiated monkeys that subsequently developed diabetes (Rad-DM)
were compared. Prior radiation exposure resulted in persistent skeletal muscle
ECM changes, including a relative overabundance of collagen IV and a trend toward
increased transforming growth factor-beta1. Preservation of microvascular markers
differentiated the irradiated diabetic and nondiabetic groups. Microvascular
density and plasma nitrate and heat shock protein 90 levels were lower in Rad-DM
than Rad-CTL. These results are consistent with a protective effect of abundant
microvasculature in maintaining glycemic control within radiation-induced
fibrotic muscle.
PMID- 28701322
TI - Functional and neurochemical characterization of angiotensin type 1A receptor
expressing neurons in the nucleus of the solitary tract of the mouse.
AB - Angiotensin II acts via two main receptors within the central nervous system,
with the type 1A receptor (AT1AR) most widely expressed in adult neurons.
Activation of the AT1R in the nucleus of the solitary tract (NTS), the principal
nucleus receiving central synapses of viscerosensory afferents, modulates
cardiovascular reflexes. Expression of the AT1R occurs in high density within the
NTS of most mammals, including humans, but the fundamental electrophysiological
and neurochemical characteristics of the AT1AR-expressing NTS neurons are not
known. To address this, we have used a transgenic mouse, in which the AT1AR
promoter drives expression of green fluorescent protein (GFP). Approximately one
third of AT1AR-expressing neurons express the catecholamine-synthetic enzyme
tyrosine hydroxylase (TH), and a subpopulation of these stained for the
transcription factor paired-like homeobox 2b (Phox2b). A third group, comprising
approximately two-thirds of the AT1AR-expressing NTS neurons, showed Phox2b
immunoreactivity alone. A fourth group in the ventral subnucleus expressed
neither TH nor Phox2b. In whole cell recordings from slices in vitro, AT1AR-GFP
neurons exhibited voltage-activated potassium currents, including the transient
outward current and the M-type potassium current. In two different mouse strains,
both AT1AR-GFP neurons and TH-GFP neurons showed similar AT1AR-mediated
depolarizing responses to superfusion with angiotensin II. These data provide a
comprehensive description of AT1AR-expressing neurons in the NTS and increase our
understanding of the complex actions of this neuropeptide in the modulation of
viscerosensory processing.
PMID- 28701324
TI - 40-4-40: educational and economic outcomes of a free, international surgical
training event.
AB - PURPOSE OF STUDY: To demonstrate a model for delivery of an international
surgical training event, and demonstrate its educational and economic outcomes.
STUDY DESIGN: The Association of Surgeons in Training (ASiT) ran a course series
on 16 January 2016 across the UK and Ireland. A mandatory, self-reported, online
questionnaire collected delegate feedback, using 5-point Likert Scales, and a
NetPromoter feedback tool. Precourse and postcourse matched questionnaires were
collected for 'Foundation Skills in Surgery' (FSS) courses. Paired economic
analysis was performed. Statistical analysis was carried out using RStudio
(V.3.1.1 Boston, Massachusetts, USA). RESULTS: Forty courses were held across the
UK and Ireland (65.0% technical, 35.0% non-technical), with 184 faculty members.
Of 570 delegates, 529 fully completed the feedback survey (92.8% response rate);
56.5% were male. The median age was 26 years (range: 18-67 years). The mean
overall course NetPromoter Score was 8.7 out of 10. On logistic regression high
NetPromoter Score was associated with completing a Foundation Skills in Surgery
course (R=0.44, OR: 1.49, p=0.025) and having clear learning outcomes (R=0.72,
OR: 2.04, p=0.029) but not associated with specialty, course style or teaching
style. For Foundation Skills in Surgery courses, delegates reported increased
commitment to a career in surgery (p<0.001), confidence with basic surgical
skills (p<0.001) and confidence with assisting in theatre (p<0.001). A comparable
cost saving of L231,462.37 was calculated across the 40 courses. CONCLUSION: The
ASiT '40-4-40' event demonstrated the diversity and depth of surgical training,
with 40 synchronous technical and non-technical courses, demonstrable educational
benefit and a significant cost saving to surgical trainees.
PMID- 28701323
TI - Renal denervation attenuates hypertension but not salt sensitivity in ETB
receptor-deficient rats.
AB - Hypertension is a prevalent pathology that increases risk for numerous
cardiovascular diseases. Because the etiology of hypertension varies across
patients, specific and effective therapeutic approaches are needed. The role of
renal sympathetic nerves is established in numerous forms of hypertension, but
their contribution to salt sensitivity and interaction with factors such as
endothelin-1 are poorly understood. Rats deficient of functional ETB receptors
(ETB-def) on all tissues except sympathetic nerves are hypertensive and exhibit
salt-sensitive increases in blood pressure. We hypothesized that renal
sympathetic nerves contribute to hypertension and salt sensitivity in ETB-def
rats. The hypothesis was tested through bilateral renal sympathetic nerve
denervation and measuring blood pressure during normal salt (0.49% NaCl) and high
salt (4.0% NaCl) diets. Denervation reduced mean arterial pressure in ETB-def
rats compared with sham-operated controls by 12 +/- 3 (SE) mmHg; however,
denervation did not affect the increase in blood pressure after 2 wk of high-salt
diet (+19 +/- 3 vs. +16 +/- 3 mmHg relative to normal salt diet; denervated vs.
sham, respectively). Denervation reduced cardiac sympathetic-to-parasympathetic
tone [low frequency-high frequency (LF/HF)] during normal salt diet and vasomotor
LF/HF tone during high-salt diet in ETB-def rats. We conclude that the renal
sympathetic nerves contribute to the hypertension but not to salt sensitivity of
ETB-def rats.
PMID- 28701325
TI - Celebrating 35 Years of the AJNR: July 1982 edition.
PMID- 28701327
TI - Tetanus neurotoxin: conformational plasticity as an adaptive strategy.
PMID- 28701326
TI - Abeta seeding potency peaks in the early stages of cerebral beta-amyloidosis.
AB - Little is known about the extent to which pathogenic factors drive the
development of Alzheimer's disease (AD) at different stages of the long
preclinical and clinical phases. Given that the aggregation of the beta-amyloid
peptide (Abeta) is an important factor in AD pathogenesis, we asked whether Abeta
seeds from brain extracts of mice at different stages of amyloid deposition
differ in their biological activity. Specifically, we assessed the effect of age
on Abeta seeding activity in two mouse models of cerebral Abeta amyloidosis
(APPPS1 and APP23) with different ages of onset and rates of progression of Abeta
deposition. Brain extracts from these mice were serially diluted and inoculated
into host mice. Strikingly, the seeding activity (seeding dose SD50) in extracts
from donor mice of both models reached a plateau relatively early in the
amyloidogenic process. When normalized to total brain Abeta, the resulting
specific seeding activity sharply peaked at the initial phase of Abeta
deposition, which in turn is characterized by a temporary several-fold increase
in the Abeta42/Abeta40 ratio. At all stages, the specific seeding activity of the
APPPS1 extract was higher compared to that of APP23 brain extract, consistent
with a more important contribution of Abeta42 than Abeta40 to seed activity. Our
findings indicate that the Abeta seeding potency is greatest early in the
pathogenic cascade and diminishes as Abeta increasingly accumulates in brain. The
present results provide experimental support for directing anti-Abeta
therapeutics to the earliest stage of the pathogenic cascade, preferably before
the onset of amyloid deposition.
PMID- 28701328
TI - Inpatient Mortality Risk Scores and Postdischarge Events in Hospitalized Heart
Failure Patients: A Community-Based Study.
AB - BACKGROUND: The Acute Decompensated Heart Failure National Registry (ADHERE) and
Get With The Guidelines (GWTG) registries have developed simple heart failure
(HF) in-hospital mortality risk scores. We hypothesized that HF scores predictive
of in-hospital mortality would perform as well for early postdischarge mortality
risk stratification. METHODS AND RESULTS: In this single-center, community-based,
retrospective study of all consecutive primary HF hospitalizations (6203
hospitalizations in 3745 patients) from 2000 to 2013, the ADHERE and GWTG risk
scores were calculated from admission data. There were 176 (3.0%) and 399 (6.7%),
869 (14.7%), and 1272 (21.5%) deaths in-hospital and at 30, 90, and 180 days
postdischarge, respectively. The GWTG but not ADHERE risk score was well
calibrated for in-hospital mortality. Both the ADHERE (C statistic 0.66 and 0.67,
0.64, and 0.64) and GWTG (C statistic 0.74 and 0.73, 0.71, and 0.70) HF risk
scores were similarly predictive of in-hospital and 30-, 90-, and 180-day
postdischarge mortality. The ADHERE risk score identified 10% and the GWTG risk
score identified 20% of hospitalizations where 180-day postdischarge mortality
was 50%, a prognostic bench mark for hospice referral. In contrast,
hospitalizations characterized as lowest risk by the ADHERE (57% of
hospitalizations; 180-day mortality 16.2%) or GWTG score (20% of
hospitalizations; 180-day mortality 8.0%) had substantially lower mortality (odds
ratios high versus low risk of 5-8 [ADHERE] and 11-18 [GWTG] across time points;
P<0.0001 for all). CONCLUSIONS: The simple ADHERE and GWTG scores stratify
hospitalized HF patients for both inpatient and early postdischarge mortality
risk, allowing comprehensive risk assessment on admission.
PMID- 28701329
TI - Multisubunit DNA-Dependent RNA Polymerases from Vaccinia Virus and Other
Nucleocytoplasmic Large-DNA Viruses: Impressions from the Age of Structure.
AB - The past 17 years have been marked by a revolution in our understanding of
cellular multisubunit DNA-dependent RNA polymerases (MSDDRPs) at the structural
level. A parallel development over the past 15 years has been the emerging story
of the giant viruses, which encode MSDDRPs. Here we link the two in an attempt to
understand the specialization of multisubunit RNA polymerases in the domain of
life encompassing the large nucleocytoplasmic DNA viruses (NCLDV), a superclade
that includes the giant viruses and the biochemically well-characterized poxvirus
vaccinia virus. The first half of this review surveys the recently determined
structural biology of cellular RNA polymerases for a microbiology readership. The
second half discusses a reannotation of MSDDRP subunits from NCLDV families and
the apparent specialization of these enzymes by virus family and by subunit with
regard to subunit or domain loss, subunit dissociability, endogenous control of
polymerase arrest, and the elimination/customization of regulatory interactions
that would confer higher-order cellular control. Some themes are apparent in
linking subunit function to structure in the viral world: as with cellular RNA
polymerases I and III and unlike cellular RNA polymerase II, the viral enzymes
seem to opt for speed and processivity and seem to have eliminated domains
associated with higher-order regulation. The adoption/loss of viral RNA
polymerase proofreading functions may have played a part in matching intrinsic
mutability to genome size.
PMID- 28701331
TI - Lassa fever.
PMID- 28701330
TI - Oral administration of pyrophosphate inhibits connective tissue calcification.
AB - Various disorders including pseudoxanthoma elasticum (PXE) and generalized
arterial calcification of infancy (GACI), which are caused by inactivating
mutations in ABCC6 and ENPP1, respectively, present with extensive tissue
calcification due to reduced plasma pyrophosphate (PPi). However, it has always
been assumed that the bioavailability of orally administered PPi is negligible.
Here, we demonstrate increased PPi concentration in the circulation of humans
after oral PPi administration. Furthermore, in mouse models of PXE and GACI, oral
PPi provided via drinking water attenuated their ectopic calcification phenotype.
Noticeably, provision of drinking water with 0.3 mM PPi to mice heterozygous for
inactivating mutations in Enpp1 during pregnancy robustly inhibited ectopic
calcification in their Enpp1-/- offspring. Our work shows that orally
administered PPi is readily absorbed in humans and mice and inhibits connective
tissue calcification in mouse models of PXE and GACI PPi, which is recognized as
safe by the FDA, therefore not only has great potential as an effective and
extremely low-cost treatment for these currently intractable genetic disorders,
but also in other conditions involving connective tissue calcification.
PMID- 28701332
TI - Circulating RANKL and RANKL/OPG and Breast Cancer Risk by ER and PR Subtype:
Results from the EPIC Cohort.
AB - Receptor activator of nuclear factor-kappa B (RANK)-RANK ligand (RANKL) signaling
promotes mammary tumor development in experimental models. Circulating
concentrations of soluble RANKL (sRANKL) may influence breast cancer risk via
activation of RANK signaling; this may be modulated by osteoprotegerin (OPG), the
decoy receptor for RANKL. sRANKL and breast cancer risk by hormone receptor
subtype has not previously been investigated. A case-control study was nested in
the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.
This study included 1,976 incident invasive breast cancer cases [estrogen
receptor positive (ER+), n = 1,598], matched 1:1 to controls. Women were pre- or
postmenopausal at blood collection. Serum sRANKL was quantified using an ELISA,
serum OPG using an electrochemiluminescent assay. Risk ratios (RR) and 95%
confidence intervals (95% CI) were calculated using conditional logistic
regression. Associations between sRANKL and breast cancer risk differed by tumor
hormone receptor status (Phet = 0.05). Higher concentrations of sRANKL were
positively associated with risk of ER+ breast cancer [5th vs. 1st quintile RR
1.28 (95% CI, 1.01-1.63); Ptrend = 0.20], but not ER- disease. For both ER+ and
estrogen and progesterone receptor positive (ER+PR+) breast cancer, results
considering the sRANKL/OPG ratio were similar to those for sRANKL; we observed a
suggestive inverse association between the ratio and ER-PR- disease [5th vs. 1st
quintile RR = 0.60 (0.31-1.14); Ptrend = 0.03]. This study provides the first
large-scale prospective data on circulating sRANKL and breast cancer. We observed
limited evidence for an association between sRANKL and breast cancer risk. Cancer
Prev Res; 10(9); 525-34. (c)2017 AACR.
PMID- 28701333
TI - Risk of post-pregnancy hypertension in women with a history of hypertensive
disorders of pregnancy: nationwide cohort study.
AB - Objectives To determine how soon after delivery the risk of post-pregnancy
hypertension increases in women with hypertensive disorders of pregnancy and how
the risk evolves over time.Design Nationwide register based cohort study.Setting
Denmark.Populations 482 972 primiparous women with a first live birth or
stillbirth between 1995 and 2012 (cumulative incidence analyses), and 1 025 118
women with at least one live birth or stillbirth between 1978 and 2012 (Cox
regression analyses).Main outcome measures 10 year cumulative incidences of post
pregnancy hypertension requiring treatment with prescription drugs, and hazard
ratios estimated using Cox regression.Results Of women with a hypertensive
disorder of pregnancy in a first pregnancy in their 20s, 14% developed
hypertension in the first decade post partum, compared with 4% of women with
normotensive first pregnancies in their 20s. The corresponding percentages for
women with a first pregnancy in their 40s were 32% and 11%, respectively. In the
year after delivery, women with a hypertensive disorder of pregnancy had 12-fold
to 25-fold higher rates of hypertension than did women with a normotensive
pregnancy. Rates in women with a hypertensive disorder of pregnancy were
threefold to 10-fold higher 1-10 years post partum and remained twice as high
even 20 or more years later.Conclusions The risk of hypertension associated with
hypertensive disorders of pregnancy is high immediately after an affected
pregnancy and persists for more than 20 years. Up to one third of women with a
hypertensive disorder of pregnancy may develop hypertension within a decade of an
affected pregnancy, indicating that cardiovascular disease prevention in these
women should include blood pressure monitoring initiated soon after pregnancy.
PMID- 28701335
TI - No significant difference in long-term remission between psychological therapies
and antidepressants in panic disorder.
PMID- 28701334
TI - Genetic Susceptibility, Change in Physical Activity, and Long-term Weight Gain.
AB - Whether change in physical activity over time modifies the genetic susceptibility
to long-term weight gain is unknown. We calculated a BMI-genetic risk score (GRS)
based on 77 BMI-associated single nucleotide polymorphisms (SNPs) and a body fat
percentage (BF%)-GRS based on 12 BF%-associated SNPs in 9,390 women from the
Nurses' Health Study (NHS) and 5,291 men from the Health Professionals Follow-Up
Study (HPFS). We analyzed the interactions between each GRS and change in
physical activity on BMI/body weight change within five 4-year intervals from
1986 to 2006 using multivariable generalized linear models with repeated-measures
analyses. Both the BMI-GRS and the BF%-GRS were associated with long-term
increases in BMI/weight, and change in physical activity consistently interacted
with the BF%-GRS on BMI change in the NHS (P for interaction = 0.025) and HPFS (P
for interaction = 0.001). In the combined cohorts, 4-year BMI change per 10-risk
allele increment was -0.02 kg/m2 among participants with greatest increase in
physical activity and 0.24 kg/m2 among those with greatest decrease in physical
activity (P for interaction < 0.001), corresponding to 0.01 kg versus 0.63 kg
weight changes every 4 years (P for interaction = 0.001). Similar but marginal
interactions were observed for the BMI-GRS (P for interaction = 0.045). Our data
indicate that the genetic susceptibility to weight gain may be diminished by
increasing physical activity.
PMID- 28701336
TI - Internet-based cognitive behavioural therapy for young people with suicide
related behaviour (Reframe-IT): a randomised controlled trial.
AB - BACKGROUND: Suicide-related behaviours are common in young people and associated
with a range of negative outcomes. There are few evidence-based interventions;
however, cognitive behavioural therapy (CBT) shows promise. Internet delivery of
CBT is popular, with potential to increase reach and accessibility. OBJECTIVE: To
test the effectiveness of an internet-based CBT program (Reframe-IT) in reducing
suicide-related behaviours, depression, anxiety, hopelessness and improving
problem solving and cognitive and behavioural skills in school students with
suicide-related behaviours. METHODS: A parallel randomised controlled trial
testing the effectiveness of Reframe-IT plus treatment as usual (TAU) compared
with TAU alone in reducing suicidal ideation, suicide attempts, depression,
hopelessness, symptoms of anxiety, negative problem orientation and cognitive and
behavioural skill acquisition was undertaken. We recruited students experiencing
suicidal ideation from 18 schools in Melbourne, Australia, between August 2013
and December 2016. The intervention comprised eight modules of CBT delivered
online over 10 weeks with assessments conducted at baseline, 10 weeks and 22
weeks. FINDINGS: Only 50 of the planned 169 participants were recruited. There
were larger improvements in the Reframe-IT group compared with the TAU group for
the primary outcome of suicidal ideation (intervention -61.6, SD 41.6; control
47.1, SD 42.3, from baseline to 22-week follow-up intervention); however,
differences were non-significant (p=0.593). There were no increases in distress
in the majority of participants (91.1%) after completion of each module. Changes
in depression and hopelessness partly mediated the effect of acquisition of CBT
skills on suicidal ideation. CONCLUSIONS: The trial was underpowered due to
difficulties recruiting participants as a result of the complex recruitment
procedures that were used to ensure safety of participants. Although there were
no significant differences between groups, young people were safely and generally
well engaged in Reframe-IT and experienced decreases in suicidal ideation and
other symptoms as well as improvements in CBT skills. The study is the first
online intervention trial internationally to include young people demonstrating
all levels of suicide risk. CLINICAL IMPLICATIONS: Integration of internet
delivered interventions for young people with suicide-related behaviour may
result in reductions in these behaviours. Further research is needed, but
researchers should feel more confident about being able to safely undertake
research with young people who experience these behaviours. TRIAL REGISTRATION
NUMBER: ACTRN12613000864729.
PMID- 28701337
TI - Should we screen for cirrhosis?
PMID- 28701339
TI - WHO downgrades status of oseltamivir.
PMID- 28701338
TI - Lifestyle in progression from hypertensive disorders of pregnancy to chronic
hypertension in Nurses' Health Study II: observational cohort study.
AB - Objectives To study the association between lifestyle risk factors and chronic
hypertension by history of hypertensive disorders of pregnancy (HDP: gestational
hypertension and pre-eclampsia) and investigate the extent to which these risk
factors modify the association between HDP and chronic hypertension.Design
Prospective cohort study.Setting Nurses' Health Study II (1991-2013).Participants
54 588 parous women aged 32 to 59 years with data on reproductive history and
without previous chronic hypertension, stroke, or myocardial infarction.Main
outcome measure Chronic hypertension diagnosed by a physician and indicated
through nurse participant self report. Multivariable Cox proportional hazards
models were used to investigate the development of chronic hypertension
contingent on history of HDP and four lifestyle risk factors: post-pregnancy body
mass index, physical activity, adherence to the Dietary Approaches to Stop
Hypertension (DASH) diet, and dietary sodium/potassium intake. Potential effect
modification (interaction) between each lifestyle factor and previous HDP was
evaluated with the relative excess risk due to interaction.Results 10% (n=5520)
of women had a history of HDP at baseline. 13 971 cases of chronic hypertension
occurred during 689 988 person years of follow-up. Being overweight or obese was
the only lifestyle factor consistently associated with higher risk of chronic
hypertension. Higher body mass index, in particular, also increased the risk of
chronic hypertension associated with history of HDP (relative excess risk due to
interaction P<0.01 for all age strata). For example, in women aged 40-49 years
with previous HDP and obesity class I (body mass index 30.0-34.9), 25% (95%
confidence interval 12% to 37%) of the risk of chronic hypertension was
attributable to a potential effect of obesity that was specific to women with
previous HDP. There was no clear evidence of effect modification by physical
activity, DASH diet, or sodium/potassium intake on the association between HDP
and chronic hypertension.Conclusion This study suggests that the risk of chronic
hypertension after HDP might be markedly reduced by adherence to a beneficial
lifestyle. Compared with women without a history of HDP, keeping a healthy weight
seems to be especially important with such a history.
PMID- 28701340
TI - CENP-F couples cargo to growing and shortening microtubule ends.
AB - Dynamic microtubule ends exert pulling and pushing forces on intracellular
membranes and organelles. However, the mechanical linkage of microtubule tips to
their cargoes is poorly understood. CENP-F is a nonmotor microtubule-binding
protein that participates in microtubule binding at kinetochores and in the
mitotic redistribution of the mitochondrial network. CENP-F-driven mitochondrial
transport is linked to growing microtubule tips, but the underlying molecular
mechanisms are unknown. Here we show that CENP-F tracks growing microtubule ends
in living cells. In vitro reconstitution demonstrates that microtubule tips can
transport mitochondria and CENP-F-coated artificial cargoes over micrometer-long
distances during both growing and shrinking phases. Based on these and previous
observations, we suggest that CENP-F might act as a transporter of mitochondria
and other cellular cargoes by attaching them to dynamic microtubule ends during
both polymerization and depolymerization of tubulin.
PMID- 28701341
TI - Computer simulations reveal mechanisms that organize nuclear dynein forces to
separate centrosomes.
AB - Centrosome separation along the surface of the nucleus at the onset of mitosis is
critical for bipolar spindle assembly. Dynein anchored on the nuclear envelope is
known to be important for centrosome separation, but it is unclear how nuclear
dynein forces are organized in an anisotropic manner to promote the movement of
centrosomes away from each other. Here we use computational simulations of
Caenorhabditis elegans embryos to address this fundamental question, testing
three potential mechanisms by which nuclear dynein may act. First, our analysis
shows that expansion of the nuclear volume per se does not generate nuclear
dynein-driven separation forces. Second, we find that steric interactions between
microtubules and centrosomes contribute to robust onset of nuclear dynein
mediated centrosome separation. Third, we find that the initial position of
centrosomes, between the male pronucleus and cell cortex at the embryo posterior,
is a key determinant in organizing microtubule aster asymmetry to power nuclear
dynein-dependent separation. Overall our work reveals that accurate initial
centrosome position, together with steric interactions, ensures proper
anisotropic organization of nuclear dynein forces to separate centrosomes, thus
ensuring robust bipolar spindle assembly.
PMID- 28701342
TI - Activating transcription factor 3 promotes loss of the acinar cell phenotype in
response to cerulein-induced pancreatitis in mice.
AB - Pancreatitis is a debilitating disease of the exocrine pancreas that, under
chronic conditions, is a major susceptibility factor for pancreatic ductal
adenocarcinoma (PDAC). Although down-regulation of genes that promote the mature
acinar cell fate is required to reduce injury associated with pancreatitis, the
factors that promote this repression are unknown. Activating transcription factor
3 (ATF3) is a key mediator of the unfolded protein response, a pathway rapidly
activated during pancreatic insult. Using chromatin immunoprecipitation followed
by next-generation sequencing, we show that ATF3 is bound to the transcriptional
regulatory regions of >30% of differentially expressed genes during the
initiation of pancreatitis. Of importance, ATF3-dependent regulation of these
genes was observed only upon induction of pancreatitis, with pathways involved in
inflammation, acinar cell differentiation, and cell junctions being specifically
targeted. Characterizing expression of transcription factors that affect acinar
cell differentiation suggested that acinar cells lacking ATF3 maintain a mature
cell phenotype during pancreatitis, a finding supported by maintenance of
junctional proteins and polarity markers. As a result, Atf3-/- pancreatic tissue
displayed increased tissue damage and inflammatory cell infiltration at early
time points during injury but, at later time points, showed reduced acinar-to
duct cell metaplasia. Thus our results reveal a critical role for ATF3 as a key
regulator of the acinar cell transcriptional response during injury and may
provide a link between chronic pancreatitis and PDAC.
PMID- 28701343
TI - LET-99 functions in the astral furrowing pathway, where it is required for myosin
enrichment in the contractile ring.
AB - The anaphase spindle determines the position of the cytokinesis furrow, such that
the contractile ring assembles in an equatorial zone between the two spindle
poles. Contractile ring formation is mediated by RhoA activation at the equator
by the centralspindlin complex and midzone microtubules. Astral microtubules also
inhibit RhoA accumulation at the poles. In the Caenorhabditis elegans one-cell
embryo, the astral microtubule-dependent pathway requires anillin, NOP-1, and LET
99. LET-99 is well characterized for generating the asymmetric cortical
localization of the Galpha-dependent force-generating complex that positions the
spindle during asymmetric division. However, whether the role of LET-99 in
cytokinesis is specific to asymmetric division and whether it acts through Galpha
to promote furrowing are unclear. Here we show that LET-99 contributes to
furrowing in both asymmetrically and symmetrically dividing cells, independent of
its function in spindle positioning and Galpha regulation. LET-99 acts in a
pathway parallel to anillin and is required for myosin enrichment into the
contractile ring. These and other results suggest a positive feedback model in
which LET-99 localizes to the presumptive cleavage furrow in response to the
spindle and myosin. Once positioned there, LET-99 enhances myosin accumulation to
promote furrowing in both symmetrically and asymmetrically dividing cells.
PMID- 28701344
TI - Syp1 regulates the clathrin-mediated and clathrin-independent endocytosis of
multiple cargo proteins through a novel sorting motif.
AB - Internalization of proteins from the plasma membrane (PM) allows for cell-surface
composition regulation, signaling of network modulation, and nutrient uptake.
Clathrin-mediated endocytosis (CME) is a major internalization route for PM
proteins. During CME, endocytic adaptor proteins bind cargoes at the cell surface
and link them to the PM and clathrin coat. Muniscins are a conserved family of
endocytic adaptors, including Syp1 in budding yeast and its mammalian orthologue,
FCHo1. These adaptors bind cargo via a C-terminal MU-homology domain (MUHD);
however, few cargoes exhibiting muniscin-dependent endocytosis have been
identified, and the sorting sequence recognized by the uHD is unknown. To reveal
Syp1 cargo-sorting motifs, we performed a phage display screen and used
biochemical methods to demonstrate that the Syp1 uHD binds DxY motifs in the
previously identified Syp1 cargo Mid2 and the v-SNARE Snc1. We also executed an
unbiased visual screen, which identified the peptide transporter Ptr2 and the
ammonium permease Mep3 as Syp1 cargoes containing DxY motifs. Finally, we
determined that, in addition to regulating cargo entry through CME, Syp1 can
promote internalization of Ptr2 through a recently identified clathrin
independent endocytic pathway that requires the Rho1 GTPase. These findings
elucidate the mechanism of Syp1 cargo recognition and its role in trafficking.
PMID- 28701345
TI - TRIM9-dependent ubiquitination of DCC constrains kinase signaling, exocytosis,
and axon branching.
AB - Extracellular netrin-1 and its receptor deleted in colorectal cancer (DCC)
promote axon branching in developing cortical neurons. Netrin-dependent
morphogenesis is preceded by multimerization of DCC, activation of FAK and Src
family kinases, and increases in exocytic vesicle fusion, yet how these
occurrences are linked is unknown. Here we demonstrate that tripartite motif
protein 9 (TRIM9)-dependent ubiquitination of DCC blocks the interaction with and
phosphorylation of FAK. Upon netrin-1 stimulation TRIM9 promotes DCC
multimerization, but TRIM9-dependent ubiquitination of DCC is reduced, which
promotes an interaction with FAK and subsequent FAK activation. We found that
inhibition of FAK activity blocks elevated frequencies of exocytosis in vitro and
elevated axon branching in vitro and in vivo. Although FAK inhibition decreased
soluble N-ethylmaleimide attachment protein receptor (SNARE)-mediated exocytosis,
assembled SNARE complexes and vesicles adjacent to the plasma membrane increased,
suggesting a novel role for FAK in the progression from assembled SNARE complexes
to vesicle fusion in developing murine neurons.
PMID- 28701346
TI - The N-terminus of IFT46 mediates intraflagellar transport of outer arm dynein and
its cargo-adaptor ODA16.
AB - Cilia are assembled via intraflagellar transport (IFT). The IFT machinery is
composed of motors and multisubunit particles, termed IFT-A and IFT-B, that carry
cargo into the cilium. Knowledge of how the IFT subunits interact with their
cargo is of critical importance for understanding how the unique ciliary domain
is established. We previously reported a Chlamydomonas mutant, ift46-1, that
fails to express the IFT-B protein IFT46, has greatly reduced levels of other IFT
B proteins, and assembles only very short flagella. A spontaneous suppression of
ift46-1 restored IFT-B levels and enabled growth of longer flagella, but the
flagella lacked outer dynein arms. Here we show that the suppression is due to
insertion of the transposon MRC1 into the ift46-1 allele, causing the expression
of a fusion protein including the IFT46 C-terminal 240 amino acids. The IFT46 C
terminus can assemble into and stabilize IFT-B but does not support transport of
outer arm dynein into flagella. ODA16, a cargo adaptor specific for outer arm
dynein, also fails to be imported into the flagella in the absence of the IFT46 N
terminus. We conclude that the IFT46 N-terminus, ODA16, and outer arm dynein
interact for IFT of the latter.
PMID- 28701347
TI - A casein kinase 1 prevents expulsion of the oocyte meiotic spindle into a polar
body by regulating cortical contractility.
AB - During female meiosis, haploid eggs are generated from diploid oocytes. This
reduction in chromosome number occurs through two highly asymmetric cell
divisions, resulting in one large egg and two small polar bodies. Unlike mitosis,
where an actomyosin contractile ring forms between the sets of segregating
chromosomes, the meiotic contractile ring forms on the cortex adjacent to one
spindle pole, then ingresses down the length of the spindle to position itself at
the exact midpoint between the two sets of segregating chromosomes. Depletion of
casein kinase 1 gamma (CSNK-1) in Caenorhabditis elegans led to the formation of
large polar bodies that contain all maternal DNA, because the contractile ring
ingressed past the spindle midpoint. Depletion of CSNK-1 also resulted in the
formation of deep membrane invaginations during meiosis, suggesting an effect on
cortical myosin. Both myosin and anillin assemble into dynamic rho-dependent
cortical patches that rapidly disassemble in wild-type embryos. CSNK-1 was
required for disassembly of both myosin patches and anillin patches. Disassembly
of anillin patches was myosin independent, suggesting that CSNK-1 prevents
expulsion of the entire meiotic spindle into a polar body by negatively
regulating the rho pathway rather than through direct inhibition of myosin.
PMID- 28701348
TI - DNA damage regulates direct association of TOR kinase with the RNA polymerase II
transcribed HMO1 gene.
AB - The mechanistic target of rapamycin complex 1 (mTORC1) senses nutrient
sufficiency and cellular stress. When mTORC1 is inhibited, protein synthesis is
reduced in an intricate process that includes a concerted down-regulation of
genes encoding rRNA and ribosomal proteins. The Saccharomyces cerevisiae high
mobility group protein Hmo1p has been implicated in coordinating this response to
mTORC1 inhibition. We show here that Tor1p binds directly to the HMO1 gene (but
not to genes that are not linked to ribosome biogenesis) and that the presence of
Tor1p is associated with activation of gene activity. Persistent induction of DNA
double-strand breaks or mTORC1 inhibition by rapamycin results in reduced levels
of HMO1 mRNA, but only in the presence of Tor1p. This down-regulation is
accompanied by eviction of Ifh1p and recruitment of Crf1p, followed by concerted
dissociation of Hmo1p and Tor1p. These findings uncover a novel role for TOR
kinase in control of gene activity by direct association with an RNA polymerase
II-transcribed gene.
PMID- 28701349
TI - Actin cytoskeleton-dependent regulation of corticotropin-releasing factor
receptor heteromers.
AB - Stress responses are highly nuanced and variable, but how this diversity is
achieved by modulating receptor function is largely unknown. Corticotropin
releasing factor receptors (CRFRs), class B G protein-coupled receptors, are
pivotal in mediating stress responses. Here we show that the two known CRFRs
interact to form heteromeric complexes in HEK293 cells coexpressing both CRFRs
and in vivo in mouse pancreas. Coimmunoprecipitation and mass spectrometry
confirmed the presence of both CRF1R and CRF2betaR, along with actin in these
heteromeric complexes. Inhibition of actin filament polymerization prevented the
transport of CRF2betaR to the cell surface but had no effect on CRF1R. Transport
of CRF1R when coexpressed with CRF2betaR became actin dependent. Simultaneous
stimulation of cells coexpressing CRF1R+CRF2betaR with their respective high
affinity agonists, CRF+urocortin2, resulted in approximately twofold increases in
peak Ca2+ responses, whereas stimulation with urocortin1 that binds both
receptors with 10-fold higher affinity did not. The ability of CRFRs to form
heteromeric complexes in association with regulatory proteins is one mechanism to
achieve diverse and nuanced function.
PMID- 28701350
TI - Effectiveness of interventions to improve medication use during rapid-sequence
intubation in a pediatric emergency department.
AB - PURPOSE: Results of a study to determine whether checklist-based interventions
improved the selection and administration of rapid-sequence intubation (RSI)
medications in a pediatric emergency department (ED) are reported. METHODS: A
retrospective study of data collected during a quality-improvement project was
conducted. Data sources included the electronic health record and video review.
The central intervention was use of a 21-item RSI checklist, which included
guidance for the physician team leader on medication selection and timing. A
quick-reference card was developed to guide staff in preparing RSI medications.
The main outcomes were (1) standard selection, defined as administration of
indicated medications and avoidance of medications not indicated, and (2)
efficient administration, defined as an interval of <30 seconds from sedative to
neuromuscular blocker (NMB) infusion. RESULTS: A total of 253 consecutive
patients underwent RSI during 3 consecutive periods: the historical
(preimprovement) period (n = 136), the checklist only period (n = 68), and the
checklist/card period (n = 49). The rate of standard selection of 3 RSI
medications (atropine, lidocaine, and rocuronium) did not improve. The rate of
efficient sedative and NMB administration improved from 56% in the historical
period to 88% in the checklist period (p = 0.005). The median duration of RSI
medication administration decreased from 28 seconds (interquartile range [IQR],
23-44 seconds) in the historical period to 19 seconds (IQR, 15-25 seconds) in the
checklist/card period (p = 0.004). CONCLUSION: In a quality-improvement project
in a pediatric ED, a checklist-based intervention improved RSI medication
administration technique but not selection.
PMID- 28701351
TI - Characterization of Trichome-Expressed BAHD Acyltransferases in Petunia axillaris
Reveals Distinct Acylsugar Assembly Mechanisms within the Solanaceae.
AB - Acylsugars are synthesized in the glandular trichomes of the Solanaceae family
and are implicated in protection against abiotic and biotic stress. Acylsugars
are composed of either sucrose or glucose esterified with varying numbers of acyl
chains of differing length. In tomato (Solanum lycopersicum), acylsugar assembly
requires four acylsugar acyltransferases (ASATs) of the BAHD superfamily. Tomato
ASATs catalyze the sequential esterification of acyl-coenzyme A thioesters to the
R4, R3, R3', and R2 positions of sucrose, yielding a tetra-acylsucrose. Petunia
spp. synthesize acylsugars that are structurally distinct from those of tomato.
To explore the mechanisms underlying this chemical diversity, a Petuniaaxillaris
transcriptome was mined for trichome preferentially expressed BAHDs. A
combination of phylogenetic analyses, gene silencing, and biochemical analyses
coupled with structural elucidation of metabolites revealed that acylsugar
assembly is not conserved between tomato and petunia. In P. axillaris, tetra
acylsucrose assembly occurs through the action of four ASATs, which catalyze
sequential addition of acyl groups to the R2, R4, R3, and R6 positions. Notably,
in P. axillaris, PaxASAT1 and PaxASAT4 catalyze the acylation of the R2 and R6
positions of sucrose, respectively, and no clear orthologs exist in tomato.
Similarly, petunia acylsugars lack an acyl group at the R3' position, and
congruently, an ortholog of SlASAT3, which catalyzes acylation at the R3'
position in tomato, is absent in P. axillaris Furthermore, where putative
orthologous relationships of ASATs are predicted between tomato and petunia,
these are not supported by biochemical assays. Overall, these data demonstrate
the considerable evolutionary plasticity of acylsugar biosynthesis.
PMID- 28701352
TI - Calcium Pumps and Interacting BON1 Protein Modulate Calcium Signature, Stomatal
Closure, and Plant Immunity.
AB - Calcium signaling is essential for environmental responses including immune
responses. Here, we provide evidence that the evolutionarily conserved protein
BONZAI1 (BON1) functions together with autoinhibited calcium ATPase10 (ACA10) and
ACA8 to regulate calcium signals in Arabidopsis. BON1 is a plasma membrane
localized protein that negatively regulates the expression of immune receptor
genes and positively regulates stomatal closure. We found that BON1 interacts
with the autoinhibitory domains of ACA10 and ACA8, and the aca10 loss-of-function
(LOF) mutants have an autoimmune phenotype similar to that of the bon1 LOF
mutants. Genetic evidences indicate that BON1 positively regulates the activities
of ACA10 and ACA8. Consistent with this idea, the steady level of calcium
concentration is increased in both aca10 and bon1 mutants. Most strikingly,
cytosolic calcium oscillation imposed by external calcium treatment was altered
in aca10, aca8, and bon1 mutants in guard cells. In addition, calcium- and
pathogen-induced stomatal closure was compromised in the aca10 and bon1 mutants.
Taken together, this study indicates that ACA10/8 and BON1 physically interact on
plasma membrane and function in the generation of cytosol calcium signatures that
are critical for stomatal movement and impact plant immunity.
PMID- 28701353
TI - Knowns and unknowns in the care of pediatric familial hypercholesterolemia.
AB - Familial hypercholesterolemia (FH) is a common genetic disorder that causes
elevated LDL cholesterol levels from birth. Untreated FH accelerates
atherosclerosis and predisposes individuals to premature coronary artery disease
(CAD) in adulthood. Mendelian randomization studies have demonstrated that LDL
cholesterol has both a causal and cumulative effect on the risk of CAD. This
supports clinical recommendations that children with FH commence pharmacological
treatment from the age of 8 to 10 years, to reduce the burden of
hypercholesterolemia. Worldwide, the majority of children with FH remain
undiagnosed. Recent evidence suggests that the frequency of FH is at least 1 in
250 and this constitutes a public health issue. We review and identify the knowns
and unknowns concerning the detection and management of pediatric FH that impact
on the developing model of care for this condition.
PMID- 28701354
TI - Pleiotropic effects of apolipoprotein C3 on HDL functionality and adipose tissue
metabolic activity.
AB - APOC3 is produced mainly by the liver and intestine and approximately half of
plasma APOC3 associates with HDL. Though it was believed that APOC3 associates
with HDL by simple binding to preexisting particles, recent data support that
biogenesis of APOC3-containing HDL (APOC3-HDL) requires Abca1. Moreover, APOC3
HDL contributes to plasma triglyceride homeostasis by preventing APOC3
association with triglyceride-rich lipoproteins. Interestingly, APOC3-HDL also
shows positive correlation with the morbidly obese phenotype. However, the roles
of APOC3 in HDL functionality and adipose tissue metabolic activity remain
unknown. Therefore, here we investigated the direct effects of APOC3 expression
on HDL structure and function, as well as white adipose tissue (WAT) and brown
adipose tissue (BAT) metabolic activity. C57BL/6 mice were infected with an
adenovirus expressing human APOC3 or a recombinant attenuated control adenovirus
expressing green fluorescent protein and blood and tissue samples were collected
at 5 days postinfection. HDL was then analyzed for its apolipoprotein and lipid
composition and particle functionality. Additionally, purified mitochondria from
BAT and WAT were analyzed for uncoupling protein 1, cytochrome c (Cytc), and Cytc
oxidase subunit 4 protein levels as an indirect measure of their metabolic
activity. Serum metabolomic analysis was performed by NMR. Combined, our data
show that APOC3 modulates HDL structure and function, while it selectively
promotes BAT metabolic activation.
PMID- 28701355
TI - miR-4632 mediates PDGF-BB-induced proliferation and antiapoptosis of human
pulmonary artery smooth muscle cells via targeting cJUN.
AB - MicroRNAs (miRNAs) can regulate the proliferative status of pulmonary artery
smooth muscle cells (PASMCs), which is a core factor modulating pulmonary
vascular remodeling diseases, such as atherosclerosis and pulmonary arterial
hypertension (PAH). Our previous work has shown that miR-4632, a rarely reported
miRNA, is significantly downregulated in platelet-derived growth factor (PDGF)-BB
stimulated human pulmonary artery smooth muscle cells (HPASMCs), yet its cell
function and the underlying molecular mechanisms remain to be elucidated. Here,
we find that miR-4632 is highly expressed in HPASMCs and its expression
significantly decreased in response to different stimuli. Functional studies
revealed that miR-4632 inhibited proliferation and promoted apoptosis of HPASMCs
but had no effects on cell contraction and migration. Furthermore, the cJUN was
identified as a direct target gene of miR-4632, while knockdown of cJUN was
necessary for miR-4632-mediated HPASMC proliferation and apoptosis. In addition,
the downregulation of miR-4632 by PDGF-BB was found to associate with histone
deacetylation through the activation of PDGF receptor/phosphatidylinositol 3'
kinase/histone deacetylase 4 signaling. Finally, the expression of miR-4632 was
reduced in the serum of patients with PAH. Overall, our results suggest that miR
4632 plays an important role in regulating HPASMC proliferation and apoptosis by
suppression of cJUN, providing a novel therapeutic miRNA candidate for the
treatment of pulmonary vascular remodeling diseases. It also implies that serum
miR-4632 has the potential to serve as a circulating biomarker for PAH diagnosis.
PMID- 28701356
TI - Reciprocal regulation of miR-214 and PTEN by high glucose regulates renal
glomerular mesangial and proximal tubular epithelial cell hypertrophy and matrix
expansion.
AB - Aberrant expression of microRNAs (miRs) contributes to diabetic renal
complications, including renal hypertrophy and matrix protein accumulation.
Reduced expression of phosphatase and tensin homolog (PTEN) by hyperglycemia
contributes to these processes. We considered involvement of miR in the
downregulation of PTEN. In the renal cortex of type 1 diabetic mice, we detected
increased expression of miR-214 in association with decreased levels of PTEN and
enhanced Akt phosphorylation and fibronectin expression. Mesangial and proximal
tubular epithelial cells exposed to high glucose showed augmented expression of
miR-214. Mutagenesis studies using 3'-UTR of PTEN in a reporter construct
revealed PTEN as a direct target of miR-214, which controls its expression in
both of these cells. Overexpression of miR-214 decreased the levels of PTEN and
increased Akt activity similar to high glucose and lead to phosphorylation of its
substrates glycogen synthase kinase-3beta, PRAS40, and tuberin. In contrast,
quenching of miR-214 inhibited high-glucose-induced Akt activation and its
substrate phosphorylation; these changes were reversed by small interfering RNAs
against PTEN. Importantly, respective expression of miR-214 or anti-miR-214
increased or decreased the mammalian target of rapamycin complex 1 (mTORC1)
activity induced by high glucose. Furthermore, mTORC1 activity was controlled by
miR-214-targeted PTEN via Akt activation. In addition, neutralization of high
glucose-stimulated miR-214 expression significantly inhibited cell hypertrophy
and expression of the matrix protein fibronectin. Finally, the anti-miR-214
induced inhibition of these processes was reversed by the expression of
constitutively active Akt kinase and hyperactive mTORC1. These results uncover a
significant role of miR-214 in the activation of mTORC1 that contributes to high
glucose-induced mesangial and proximal tubular cell hypertrophy and fibronectin
expression.
PMID- 28701357
TI - A tale of two niches: differential functions for VCAM-1 in satellite cells under
basal and injured conditions.
AB - Cell-cell adhesion molecules play key roles in maintaining quiescence or
promoting activation of various stem cells in their niche. Muscle stem cells
called satellite cells (SC) are critical for skeletal muscle regeneration after
injury, but little is known about the role of adhesion molecules in regulating
the behavior of these stem cells. Vascular cell adhesion molecule-1 (VCAM-1) is a
cell-cell adhesion protein expressed on quiescent and activated SC whose function
is unknown in this context. We deleted Vcam1 from SC using an inducible Cre
recombinase in young mice. In the injured niche, Vcam1-/- SC underwent premature
lineage progression to a more differentiated state as well as apoptosis leading
to a transient delay in myofiber growth during regeneration. Apoptosis was also
increased in Vcam1-/- SC in vitro concomitant with decreased levels of
phosphorylated Akt, a prosurvival signal activated by VCAM-1 signaling in other
cell types. During muscle regeneration, we observed an influx of immune cells
expressing alpha4 integrin, a component of the major, high-affinity VCAM-1
ligand, alpha4beta1 integrin. Furthermore, alpha4 integrin mRNA and protein were
induced in SC 2 days after injury. These results suggest that SC interact with
other SC as well as immune cells through alpha4beta1 integrin in the injured
niche to promote expansion of SC. In the uninjured niche, multiple cell types
also expressed alpha4 integrin. However, only basal fusion of Vcam1-/- SC with
myofibers was decreased, contributing to decreased myofiber growth. These studies
define differential roles for VCAM-1 in SC depending on the state of their niche.
PMID- 28701358
TI - Mechanism of action of the anti-inflammatory connexin43 mimetic peptide JM2.
AB - Connexin-based therapeutics have shown the potential for therapeutic efficacy in
improving wound healing. Our previous work demonstrated that the connexin43
(Cx43) mimetic peptide juxtamembrane 2 (JM2) reduced the acute inflammatory
response to a submuscular implant model by inhibiting purinergic signaling. Given
the prospective application in improving tissue-engineered construct tolerance
that these results indicated, we sought to determine the mechanism of action for
JM2 in the present study. Using confocal microscopy, a gap-FRAP cell
communication assay, and an ethidium bromide uptake assay of hemichannel function
we found that the peptide reduced cell surface Cx43 levels, Cx43 gap junction
(GJ) size, GJ communication, and hemichannel activity. JM2 is based on the
sequence of the Cx43 microtubule binding domain, and microtubules have a
confirmed role in intracellular trafficking of Cx43 vesicles. Therefore, we
tested the effect of JM2 on Cx43-microtubule interaction and microtubule
polymerization. We found that JM2 enhanced Cx43-microtubule interaction and that
microtubule polymerization was significantly enhanced. Taken together, these data
suggest that JM2 inhibits trafficking of Cx43 to the cell surface by promoting
irrelevant microtubule polymerization and thereby reduces the number of
hemichannels in the plasma membrane available to participate in proinflammatory
purinergic signaling. Importantly, this work indicates that JM2 may have
therapeutic value in the treatment of proliferative diseases such as cancer. We
conclude that the targeted action of JM2 on Cx43 channels may improve the
tolerance of implanted tissue-engineered constructs against the innate
inflammatory response.
PMID- 28701359
TI - oxLDL induces endothelial cell proliferation via Rho/ROCK/Akt/p27kip1 signaling:
opposite effects of oxLDL and cholesterol loading.
AB - Oxidized modifications of LDL (oxLDL) play a key role in the development of
endothelial dysfunction and atherosclerosis. However, the underlying mechanisms
of oxLDL-mediated cellular behavior are not completely understood. Here, we
compared the effects of two major types of oxLDL, copper-oxidized LDL (Cu2+
oxLDL) and lipoxygenase-oxidized LDL (LPO-oxLDL), on proliferation of human
aortic endothelial cells (HAECs). Cu2+-oxLDL enhanced HAECs' proliferation in a
dose- and degree of oxidation-dependent manner. Similarly, LPO-oxLDL also
enhanced HAEC proliferation. Mechanistically, both Cu2+-oxLDL and LPO-oxLDL
enhance HAEC proliferation via activation of Rho, Akt phosphorylation, and a
decrease in the expression of cyclin-dependent kinase inhibitor 1B (p27kip1).
Both Cu2+-oxLDL or LPO-oxLDL significantly increased Akt phosphorylation, whereas
an Akt inhibitor, MK2206, blocked oxLDL-induced increase in HAEC proliferation.
Blocking Rho with C3 or its downstream target ROCK with Y27632 significantly
inhibited oxLDL-induced Akt phosphorylation and proliferation mediated by both
Cu2+- and LPO-oxLDL. Activation of RhoA was blocked by Rho-GDI-1, which also
abrogated oxLDL-induced Akt phosphorylation and HAEC proliferation. In contrast,
blocking Rac1 in these cells had no effect on oxLDL-induced Akt phosphorylation
or cell proliferation. Moreover, oxLDL-induced Rho/Akt signaling downregulated
cell cycle inhibitor p27kip1 Preloading these cells with cholesterol, however,
prevented oxLDL-induced Akt phosphorylation and HAEC proliferation. These
findings provide a new understanding of the effects of oxLDL on endothelial
proliferation, which is essential for developing new treatments against
neovascularization and progression of atherosclerosis.
PMID- 28701360
TI - Multicentre, randomised clinical trial of paediatric concussion assessment of
rest and exertion (PedCARE): a study to determine when to resume physical
activities following concussion in children.
AB - INTRODUCTION: Rest until symptom-free, followed by a progressive stepwise return
to activities, is often prescribed in the management of paediatric concussions.
Recent evidence suggests prolonged rest may hinder recovery, and early resumption
of physical activity may be associated with more rapid recovery postconcussion.
The primary objective is to determine whether the early reintroduction of non
contact physical activity beginning 72 hours postinjury reduces postconcussive
symptoms at 2 weeks in children following an acute concussion as compared with a
rest until asymptomatic protocol. METHODS AND ANALYSIS: This study is a
randomised clinical trial across three Canadian academic paediatric emergency
departments. A total of 350 participants, aged 10-17.99 years, who present within
48 hours of an acute concussion, will be recruited and randomly assigned to
either the study intervention protocol (resumption of physical activity 72 hours
postconcussion even if experiencing symptoms) or physical rest until fully
asymptomatic. Participants will document their daily physical and cognitive
activities. Follow-up questionnaires will be completed at 1, 2 and 4 weeks
postinjury. Compliance with the intervention will be measured using an
accelerometer (24 hours/day for 14 days). Symptoms will be measured using the
validated Health and Behaviour Inventory. A linear multivariable model, adjusting
for site and prognostically important covariates, will be tested to determine
differences between groups. The proposed protocol adheres to the RCT-CONSORT
guidelines. DISCUSSION: This trial will determine if early resumption of non
contact physical activity following concussion reduces the burden of concussion
and will provide healthcare professionals with the evidence by which to recommend
the best timing of reintroducing physical activities. TRIAL REGISTRATION NUMBER:
Trial identifier (Clinicaltrials.gov) NCT02893969.
PMID- 28701361
TI - Health promotion through sport: international sport federations' priorities,
actions and opportunities.
AB - OBJECTIVE: To identify areas of priority and activity for international
sportsfederations (IFs) with respect to athlete health and safety, and global
health. Results serve to direct the work of the Association of Summer Olympic IF
Medical and Scientific Consultative Group, the International Olympic Committee
and to influence IFs' planning and priorities. METHODS: The 28 IFs participating
in the Summer Olympic Games (2016) were asked to rank the relative importance of
11 health-related topics and to report their activities or research initiatives
on 27 identified topics using an electronic survey. A comparison with a similar
survey (2012) was made. RESULTS: The response rate was 100%. In general, the
'fight against doping' had the highest priority followed by 'image as a safe
sport'. The topics with the lowest importance ratings were 'increasing the number
of elite athletes', and 'health of the general population'. Despite ranking
'health of your athletes,' as a top priority, IFs are not addressing all aspects
of athlete health. In comparison with 2012, there was a significant decrease in
priority for IFs is 'health of the general population'. CONCLUSION: Despite the
widespread knowledge of the importance of the promotion of physical activity
(sport) on global health, the decreasing priority and programming of the IFs on
physical activity promotion is concerning. Although IFs have prioritised the
protection of the health of elite athletes, there are gaps in programming
demonstrating that IFs are missing important areas of athlete health. Improving
recreational athlete health programming could also benefit population health as
well as improve IF fan base and sport participation.
PMID- 28701362
TI - Accuracy of the ECG for differential diagnosis between hypertrophic
cardiomyopathy and athlete's heart: comparison between the European Society of
Cardiology (2010) and International (2017) criteria.
AB - BACKGROUND: Interpretation of the athlete's ECG is based on differentiation
between benign ECG changes and potentially pathological abnormalities. The aim of
the study was to compare the 2010 European Society of Cardiology (ESC) and the
2017 International criteria for differential diagnosis between hypertrophic
cardiomyopathy (HCM) and athlete's heart. METHODS: The study populations included
200 patients with HCM and 563 athletes grouped as follows: 'group 1', including
normal ECG and isolated increase of QRS voltages, which are considered non
pathologic according to ESC and International criteria; 'group 2', including left
atrial enlargement or left axis deviation in isolation and Q-waves with an
amplitude >=4 mm but <25% of the ensuing R-wave and a duration <0.04 s which are
considered pathologic according to the ESC but not according to the International
criteria; and 'group 3', including abnormalities which are considered pathologic
according to ESC and International criteria. RESULTS: Overall, the 2010 ESC
criteria showed a sensitivity of 95.5% and a specificity of 86.9%. Considering
group 2 ECG changes as normal according to the International criteria led to a
statistically significant (p<0.001) increase of specificity to 95.9%, associated
with a non-significant (p=0.47) reduction of sensitivity to 93%. Among patients
with HCM, there was a significant increase of maximal left ventricular wall
thickness from group 1 to 3 (p=0.02). CONCLUSIONS: The use of 2017 International
criteria is associated with a substantial increase in specificity and a marginal
decrease in sensitivity for differential diagnosis between HCM and athlete's
heart.
PMID- 28701363
TI - Infographic: Ankle sprain treatment and prevention timeline.
PMID- 28701364
TI - Infographic: Sports Biostatisticians as a critical member of all sports science
and medical teams for injury prevention.
PMID- 28701365
TI - McKenzie Method of Mechanical Diagnosis and Therapy was slightly more effective
than placebo for pain, but not for disability, in patients with chronic non
specific low back pain: a randomised placebo controlled trial with short and
longer term follow-up.
AB - BACKGROUND: The McKenzie Method of Mechanical Diagnosis and Therapy (MDT) is one
of the exercise approaches recommended by low back pain (LBP) guidelines. We
investigated the efficacy of MDT compared with placebo in patients with chronic
LBP. METHODS: This was a prospectively registered, two-arm randomised placebo
controlled trial, with a blinded assessor. A total of 148 patients seeking care
for chronic LBP were randomly allocated to either MDT (n=74) or placebo (n=74).
Patients from both groups received 10 treatment sessions over 5 weeks. Patients
from both groups also received an educational booklet. Clinical outcomes were
obtained at the end of treatment (5 weeks) and 3, 6 and 12 months after
randomisation. Primary outcomes were pain intensity and disability at the end of
treatment (5 weeks). We also conducted a subgroup analysis to identify potential
treatment effect modifiers that could predict a better response to MDT treatment.
RESULTS: The MDT group had greater improvements in pain intensity at the end of
treatment (mean difference (MD) -1.00, 95% CI -2.09 to -0.01) but not for
disability (MD -0.84, 95% CI -2.62 to 0.93). We did not detect between-group
differences for any secondary outcomes, nor were any treatment effect modifiers
identified. Patients did not report any adverse events. CONCLUSION: We found a
small and likely not clinically relevant difference in pain intensity favouring
the MDT method immediately at the end of 5 weeks of treatment but not for
disability. No other difference was found for any of the primary or secondary
outcomes at any follow-up times. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov
(NCT02123394).
PMID- 28701366
TI - Evidence in support of the call to ban the tackle and harmful contact in school
rugby: a response to World Rugby.
AB - In a paper published in BJSM (June 2016), World Rugby employees Ross Tucker and
Martin Raftery and a third coauthor Evert Verhagen took issue with the recent
call to ban tackling in school rugby in the UK and Ireland. That call (to ban
tackling) was supported by a systematic review published in BJSM Tucker et al
claim that: (1) the mechanisms and risk factors for injury along with the
incidence and severity of injury in youth rugby union have not been thoroughly
identified or understood; (2) rugby players are at no greater risk of injury than
other sports people, (3) this is particularly the case for children under 15
years and (4) removing the opportunity to learn the tackle from school pupils
might increase rates of injuries. They conclude that a ban 'may be unnecessary
and may also lead to unintended consequences such as an increase in the risk of
injury later in participation.' Here we aim to rebut the case by Tucker et al We
share new research that extends the findings of our original systematic review
and meta-analysis. A cautionary approach requires the removal of the tackle from
school rugby as the quickest and most effective method of reducing high injury
rates in youth rugby, a public health priority.
PMID- 28701367
TI - FDG-PET-driven consolidation strategy in diffuse large B-cell lymphoma: final
results of a randomized phase 2 study.
AB - Dose-dense induction and up-front consolidation with autologous stem cell
transplantation (ASCT) remain controversial issues when treating patients with
high-risk diffuse large B-cell lymphoma. GELA designed a randomized phase 2 trial
evaluating the efficacy of either rituximab, doxorubicin, cyclophosphamide,
vindesine, bleomycin, prednisone (R-ACVBP) or rituximab, cyclophosphamide,
doxorubicin, vincristine, prednisone (R-CHOP14) induction and a positron emission
tomography (PET)-driven ASCT or standard immunochemotherapy (SIC) consolidation
in age-adjusted international prognosis index 2 (aaIPI2)-aaIPI3 patients. PET was
performed at baseline, after 2 (PET2) and 4 (PET4) induction cycles, and
centrally assessed using international harmonization project (IHP) criteria. PET2
/PET4- patients were assigned SIC, PET2+/PET4- patients were assigned ASCT, and
PET4+ patients were treated with the investigator's choice. The primary end-point
was the 2007 international working group complete response (CR) rate after
induction. Change in maximum standard uptake value (DeltaSUVmax) after PET
assessment was explored. Two hundred eleven patients were randomly assigned to R
ACVBP (n = 109) or R-CHOP14 (n = 102). PET4-/CR rates were 53%/47% with R-ACVBP
and 41%/39% with R-CHOP14 (CR 95% confidence interval [CI], 38%-67% and 28%-54%,
respectively; P = .076). Consolidation in the R-ACVBP and R-CHOP14 groups was SIC
in 26% and 23% of patients and ASCT in 28% and 18% of patients, respectively.
PET4 positivity was higher with R-CHOP14 vs R-ACVBP (54% vs 41%; P = .08),
leading to more salvage therapy (37% vs 26%; P = .07) and lower event-free
survival (EFS; 4-year EFS, 31% vs 43%; P < .01), but progression-free survival
(PFS) and overall survival (OS) were similar in both groups. PET2-/PET4- and
PET2+/PET4- patients had similar outcomes. Using DeltaSUVmax, 79% of the patients
were PET2-/PET4- DeltaSUVmaxPET0-4 >70% was associated with better outcome (4
year PFS, 84% vs 35%; 4-year OS, 91% vs 57%; P < .0001), whatever the
consolidation. Superiority of R-ACVBP over R-CHOP14 was not established, as IHP
criteria did not properly reflect disease control. DeltaSUVmax may help better
select patients needing an alternative to SIC, including ASCT.
PMID- 28701369
TI - Synergistic cooperation and crosstalk between MYD88L265P and mutations that
dysregulate CD79B and surface IgM.
AB - CD79B and MYD88 mutations are frequently and simultaneously detected in B cell
malignancies. It is not known if these mutations cooperate or how crosstalk
occurs. Here we analyze the consequences of CD79B and MYD88L265P mutations
individually and combined in normal activated mouse B lymphocytes. CD79B
mutations alone increased surface IgM but did not enhance B cell survival,
proliferation, or altered NF-kappaB responsive markers. Conversely, B cells
expressing MYD88L265P decreased surface IgM coupled with accumulation of
endoglycosidase H-sensitive IgM intracellularly, resembling the trafficking block
in anergic B cells repeatedly stimulated by self-antigen. Mutation or
overexpression of CD79B counteracted the effect of MYD88L265P In B cells
chronically stimulated by self-antigen, CD79B and MYD88L265P mutations in
combination, but not individually, blocked peripheral deletion and triggered
differentiation into autoantibody secreting plasmablasts. These results reveal
that CD79B and surface IgM constitute a rate-limiting checkpoint against B cell
dysregulation by MYD88L265P and provide an explanation for the co-occurrence of
MYD88 and CD79B mutations in lymphomas.
PMID- 28701368
TI - Kunkel Lecture: Fundamental immunodeficiency and its correction.
AB - "Fundamental immunodeficiency" is the inability of the encoded immune system to
protect an otherwise healthy host from every infection that could threaten its
life. In contrast to primary immunodeficiencies, fundamental immunodeficiency is
not rare but nearly universal. It results not from variation in a given host gene
but from the rate and extent of variation in the genes of other organisms. The
remedy for fundamental immunodeficiency is "adopted immunity," not to be confused
with adaptive or adoptive immunity. Adopted immunity arises from four critical
societal contributions to the survival of the human species: sanitation,
nutrition, vaccines, and antimicrobial agents. Immunologists have a great deal to
contribute to the development of vaccines and antimicrobial agents, but they have
focused chiefly on vaccines, and vaccinology is thriving. In contrast, the effect
of antimicrobial agents in adopted immunity, although fundamental, is fragile and
failing. Immunologists can aid the development of sorely needed antimicrobial
agents, and the study of antimicrobial agents can help immunologists discover
targets and mechanisms of host immunity.
PMID- 28701370
TI - Twenty-Year Progression Rate to Clinical Onset According to Autoantibody Profile,
Age, and HLA-DQ Genotype in a Registry-Based Group of Children and Adults With a
First-Degree Relative With Type 1 Diabetes.
AB - OBJECTIVE: We investigated whether islet autoantibody profile, HLA-DQ genotype,
and age influenced a 20-year progression to diabetes from first autoantibody
positivity (autoAb+) in first-degree relatives of patients with type 1 diabetes.
RESEARCH DESIGN AND METHODS: Persistently islet autoAb+ siblings and offspring (n
= 462) under 40 years of age were followed by the Belgian Diabetes Registry.
AutoAbs against insulin (IAA), GAD (GADA), IA-2 antigen (IA-2A), and zinc
transporter 8 (ZnT8A) were determined by radiobinding assay. RESULTS: The 20-year
progression rate of multiple-autoAb+ relatives (n = 194) was higher than that for
single-autoAb+ participants (n = 268) (88% vs. 54%; P < 0.001). Relatives
positive for IAA and GADA (n = 54) progressed more slowly than double-autoAb+
individuals carrying IA-2A and/or ZnT8A (n = 38; P = 0.001). In multiple-autoAb+
relatives, Cox regression analysis identified the presence of IA-2A or ZnT8A as
the only independent predictors of more rapid progression to diabetes (P <
0.001); in single-autoAb+ relatives, it identified younger age (P < 0.001), HLA
DQ2/DQ8 genotype (P < 0.001), and IAA (P = 0.028) as independent predictors of
seroconversion to multiple positivity for autoAbs. In time-dependent Cox
regression, younger age (P = 0.042), HLA-DQ2/DQ8 genotype (P = 0.009), and the
development of additional autoAbs (P = 0.012) were associated with more rapid
progression to diabetes. CONCLUSIONS: In single-autoAb+ relatives, the time to
multiple-autoAb positivity increases with age and the absence of IAA and HLA
DQ2/DQ8 genotype. The majority of multiple-autoAb+ individuals progress to
diabetes within 20 years; this occurs more rapidly in the presence of IA-2A or
ZnT8A, regardless of age, HLA-DQ genotype, and number of autoAbs. These data may
help to refine the risk stratification of presymptomatic type 1 diabetes.
PMID- 28701372
TI - Guidelines for reporting meta-epidemiological methodology research.
AB - Published research should be reported to evidence users with clarity and
transparency that facilitate optimal appraisal and use of evidence and allow
replication by other researchers. Guidelines for such reporting are available for
several types of studies but not for meta-epidemiological methodology studies.
Meta-epidemiological studies adopt a systematic review or meta-analysis approach
to examine the impact of certain characteristics of clinical studies on the
observed effect and provide empirical evidence for hypothesised associations. The
unit of analysis in meta-epidemiological studies is a study, not a patient. The
outcomes of meta-epidemiological studies are usually not clinical outcomes. In
this guideline, we adapt items from the Preferred Reporting Items for Systematic
Reviews and Meta-analyses (PRISMA) to fit the context of meta-epidemiological
studies.
PMID- 28701373
TI - Antibiotic utilisation in very low birth weight infants without sepsis or
necrotising enterocolitis is associated with multiple adverse outcomes.
PMID- 28701371
TI - Population-Based Assessment of a Biomarker-Based Screening Pathway to Aid
Diagnosis of Monogenic Diabetes in Young-Onset Patients.
AB - OBJECTIVE: Monogenic diabetes, a young-onset form of diabetes, is often
misdiagnosed as type 1 diabetes, resulting in unnecessary treatment with insulin.
A screening approach for monogenic diabetes is needed to accurately select
suitable patients for expensive diagnostic genetic testing. We used C-peptide and
islet autoantibodies, highly sensitive and specific biomarkers for discriminating
type 1 from non-type 1 diabetes, in a biomarker screening pathway for monogenic
diabetes. RESEARCH DESIGN AND METHODS: We studied patients diagnosed at age 30
years or younger, currently younger than 50 years, in two U.K. regions with
existing high detection of monogenic diabetes. The biomarker screening pathway
comprised three stages: 1) assessment of endogenous insulin secretion using
urinary C-peptide/creatinine ratio (UCPCR); 2) if UCPCR was >=0.2 nmol/mmol,
measurement of GAD and IA2 islet autoantibodies; and 3) if negative for both
autoantibodies, molecular genetic diagnostic testing for 35 monogenic diabetes
subtypes. RESULTS: A total of 1,407 patients participated (1,365 with no known
genetic cause, 34 with monogenic diabetes, and 8 with cystic fibrosis-related
diabetes). A total of 386 out of 1,365 (28%) patients had a UCPCR >=0.2
nmol/mmol, and 216 out of 386 (56%) were negative for GAD and IA2 and underwent
molecular genetic testing. Seventeen new cases of monogenic diabetes were
diagnosed (8 common Maturity Onset Diabetes of the Young [Sanger sequencing] and
9 rarer causes [next-generation sequencing]) in addition to the 34 known cases
(estimated prevalence of 3.6% [51/1,407] [95% CI 2.7-4.7%]). The positive
predictive value was 20%, suggesting a 1-in-5 detection rate for the pathway. The
negative predictive value was 99.9%. CONCLUSIONS: The biomarker screening pathway
for monogenic diabetes is an effective, cheap, and easily implemented approach to
systematically screening all young-onset patients. The minimum prevalence of
monogenic diabetes is 3.6% of patients diagnosed at age 30 years or younger.
PMID- 28701374
TI - Hospital admission rates and emergency department use in relation to glycated
hemoglobin in people with diabetes mellitus: a linkage study using electronic
medical record and administrative data in Ontario.
AB - BACKGROUND: The Canadian Primary Care Sentinel Surveillance Network (CPCSSN)
collects extensive data on primary care patients but it currently does not gather
reliable information on outcomes in other settings. The objectives of this study
were to link electronic medical record (EMR) data from Ontario patients in the
CPCSSN with administrative data from the Institute for Clinical Evaluative
Sciences (ICES), to assess the representativeness of the CPCSSN population, and
to identify people with diabetes in the CPCSSN data and describe their emergency
department (ED) visits and hospital admissions over a 2-year period (2010-2012)
by HbA1c level. METHODS: We conducted a cross-sectional study linking 2014
Ontario CPCSSN data with ICES administrative data and a retrospective cohort
study using the 2014 data extraction linked with data from the Ontario health
care registry, hospital discharge abstracts and a database of emergency
department visits. Demographics of CPCSSN patients were compared with those of
the Ontario population. Patients with a CPCSSN diagnosis of diabetes were
compared by HbA1c category for ED visits, hospital admissions and diagnosis of
diabetes-related complications. RESULTS: The linkage rate was 99%. We identified
12 358 patients with diabetes, 2356 of whom were missing data on HbAIc, for a
final sample of 10 002. Patients with diabetes had a mean age of 64 years. Those
with a higher HbA1c were younger, more likely to be male, had a lower income, had
more comorbidities and were more likely to live in rural or suburban areas than
patients with a lower HbA1c. Over the study period 31.8% of patients had 1 or
more ED visits and 13.7% had a hospital admission for a diabetes-related
complication. Patients with HbA1c greater than 8 had significantly more hospital
admissions, ED visits and diabetes-related complications than patients with a
lower HbA1c . INTERPRETATION: The linkage between EMR and administrative data was
successful. In this study population, higher HbA1c values were associated with
increased ED visits and hospital admissions, with an increasing gradient as HbA1c
increased from less than 7% to greater than 8%.
PMID- 28701375
TI - SPATA2 regulates the activation of RIPK1 by modulating linear ubiquitination.
AB - Stimulation of cells with TNFalpha leads to the formation of the TNF-R1 signaling
complex (TNF-RSC) to mediate downstream cellular fate decision. Activation of the
TNF-RSC is modulated by different types of ubiquitination and may lead to cell
death, including apoptosis and necroptosis, in both RIPK1-dependent and RIPK1
independent manners. Spata2 (spermatogenesis-associated 2) is an adaptor protein
recruited into the TNF-RSC to modulate the interaction between the linear
ubiquitin chain assembly complex (LUBAC) and the deubiquitinase CYLD
(cylindromatosis). However, the mechanism by which Spata2 regulates the
activation of RIPK1 is unclear. Here, we report that Spata2-deficient cells show
resistance to RIPK1-dependent apoptosis and necroptosis and are also partially
protected against RIPK1-independent apoptosis. Spata2 deficiency promotes M1
ubiquitination of RIPK1 to inhibit RIPK1 kinase activity. Furthermore, we provide
biochemical evidence for the USP domain of CYLD and the PUB domain of the SPATA2
complex preferentially deubiquitinating the M1 ubiquitin chain in vitro. Spata2
deficiency also promotes the activation of MKK4 and JNK and cytokine production
independently of RIPK1 kinase activity. Spata2 deficiency sensitizes mice to
systemic inflammatory response syndrome (SIRS) induced by TNFalpha, which can be
suppressed by RIPK1 inhibitor Nec-1s. Thus, Spata2 can regulate inflammatory
response and cell death in both RIPK1-dependent and RIPK1-independent manners.
PMID- 28701376
TI - The Nuclear and Mitochondrial Genomes of the Facultatively Eusocial Orchid Bee
Euglossa dilemma.
AB - Bees provide indispensable pollination services to both agricultural crops and
wild plant populations, and several species of bees have become important models
for the study of learning and memory, plant-insect interactions, and social
behavior. Orchid bees (Apidae: Euglossini) are especially important to the fields
of pollination ecology, evolution, and species conservation. Here we report the
nuclear and mitochondrial genome sequences of the orchid bee Euglossa dilemma
Bembe & Eltz. E. dilemma was selected because it is widely distributed, highly
abundant, and it was recently naturalized in the southeastern United States. We
provide a high-quality assembly of the 3.3 Gb genome, and an official gene set of
15,904 gene annotations. We find high conservation of gene synteny with the honey
bee throughout 80 MY of divergence time. This genomic resource represents the
first draft genome of the orchid bee genus Euglossa, and the first draft orchid
bee mitochondrial genome, thus representing a valuable resource to the research
community.
PMID- 28701377
TI - microRNA-206 modulates an Rtn4a/Cxcr4a/Thbs3a axis in newly forming somites to
maintain and stabilize the somite boundary formation of zebrafish embryos.
AB - Although microRNA-206 (miR-206) is known to regulate proliferation and
differentiation of muscle fibroblasts, the role of miR-206 in early-stage somite
development is still unknown. During somitogenesis of zebrafish embryos,
reticulon4a (rtn4a) is specifically repressed by miR-206. The somite boundary was
defective, and actin filaments were crossing over the boundary in either miR-206
knockdown or rtn4a-overexpressed embryos. In these treated embryos, C-X-C motif
chemokine receptor 4a (cxcr4a) was reduced, while thrombospondin 3a (thbs3a) was
increased. The defective boundary was phenocopied in either cxcr4a-knockdown or
thbs3a-overexpressed embryos. Repression of thbs3a expression by cxcr4a reduced
the occurrence of the boundary defect. We demonstrated that cxcr4a is an upstream
regulator of thbs3a and that defective boundary cells could not process
epithelialization in the absence of intracellular accumulation of the
phosphorylated focal adhesion kinase (p-FAK) in boundary cells. Therefore, in the
newly forming somites, miR-206-mediated downregulation of rtn4a increases cxcr4a.
This activity largely decreases thbs3a expression in the epithelial cells of the
somite boundary, which causes epithelialization of boundary cells through
mesenchymal-epithelial transition (MET) and eventually leads to somite boundary
formation. Collectively, we suggest that miR-206 mediates a novel pathway, the
Rtn4a/Cxcr4a/Thbs3a axis, that allows boundary cells to undergo MET and form
somite boundaries in the newly forming somites of zebrafish embryos.
PMID- 28701378
TI - Dictyostelium AMPKalpha regulates aggregate size and cell-type patterning.
AB - Starved Dictyostelium cells aggregate into groups of nearly 105 cells. AMPK is a
highly conserved serine/threonine protein kinase consisting of a catalytic and
two regulatory subunits. As multi-cellular development in Dictyostelium is
initiated upon starvation, we explored the role of the energy sensor, AMPK, which
shows significant similarity to human AMPK and is expressed throughout
development. Deletion of the ampkalpha gene results in the formation of numerous
small-sized aggregates that develop asynchronously to form few fruiting bodies
with small sori and long stalks. On the other hand, ampkalphaOE cells form
fruiting bodies with small stalks and large sori when compared with wild-type,
Ax2. A minimum of 5% ampkalpha- cells in a chimaera with Ax2 cells was sufficient
to reduce the aggregate size. Also, the conditioned media collected from
ampkalpha- cells triggered Ax2 cells to form smaller aggregates. The starved
ampkalpha- cells showed low glucose levels and formed large aggregates when
glucose was supplied exogenously. Interestingly, ampkalpha- cells exhibit
abnormal cell-type patterning with increased prestalk region and a concomitant
reduction of prespore region. In addition, there was a loss of distinct
prestalk/prespore boundary in the slugs.
PMID- 28701379
TI - Loss of clusterin shifts amyloid deposition to the cerebrovasculature via
disruption of perivascular drainage pathways.
AB - Alzheimer's disease (AD) is characterized by amyloid-beta (Abeta) peptide
deposition in brain parenchyma as plaques and in cerebral blood vessels as
cerebral amyloid angiopathy (CAA). CAA deposition leads to several clinical
complications, including intracerebral hemorrhage. The underlying molecular
mechanisms that regulate plaque and CAA deposition in the vast majority of
sporadic AD patients remain unclear. The clusterin (CLU) gene is genetically
associated with AD and CLU has been shown to alter aggregation, toxicity, and
blood-brain barrier transport of Abeta, suggesting it might play a key role in
regulating the balance between Abeta deposition and clearance in both brain and
blood vessels. Here, we investigated the effect of CLU on Abeta pathology using
the amyloid precursor protein/presenilin 1 (APP/PS1) mouse model of AD
amyloidosis on a Clu+/+ or Clu-/- background. We found a marked decrease in
plaque deposition in the brain parenchyma but an equally striking increase in CAA
within the cerebrovasculature of APP/PS1;Clu-/- mice. Surprisingly, despite the
several-fold increase in CAA levels, APP/PS1;Clu-/- mice had significantly less
hemorrhage and inflammation. Mice lacking CLU had impaired clearance of Abeta in
vivo and exogenously added CLU significantly prevented Abeta binding to isolated
vessels ex vivo. These findings suggest that in the absence of CLU, Abeta
clearance shifts to perivascular drainage pathways, resulting in fewer
parenchymal plaques but more CAA because of loss of CLU chaperone activity,
complicating the potential therapeutic targeting of CLU for AD.
PMID- 28701380
TI - Prediction of intracellular exposure bridges the gap between target- and cell
based drug discovery.
AB - Inadequate target exposure is a major cause of high attrition in drug discovery.
Here, we show that a label-free method for quantifying the intracellular
bioavailability (Fic) of drug molecules predicts drug access to intracellular
targets and hence, pharmacological effect. We determined Fic in multiple cellular
assays and cell types representing different targets from a number of therapeutic
areas, including cancer, inflammation, and dementia. Both cytosolic targets and
targets localized in subcellular compartments were investigated. Fic gives
insights on membrane-permeable compounds in terms of cellular potency and
intracellular target engagement, compared with biochemical potency measurements
alone. Knowledge of the amount of drug that is locally available to bind
intracellular targets provides a powerful tool for compound selection in early
drug discovery.
PMID- 28701381
TI - Enhanced coupling of light into a turbid medium through microscopic interface
engineering.
AB - There are many optical detection and sensing methods used today that provide
powerful ways to diagnose, characterize, and study materials. For example, the
measurement of spontaneous Raman scattering allows for remote detection and
identification of chemicals. Many other optical techniques provide unique
solutions to learn about biological, chemical, and even structural systems.
However, when these systems exist in a highly scattering or turbid medium, the
optical scattering effects reduce the effectiveness of these methods. In this
article, we demonstrate a method to engineer the geometry of the optical
interface of a turbid medium, thereby drastically enhancing the coupling
efficiency of light into the material. This enhanced optical coupling means that
light incident on the material will penetrate deeper into (and through) the
medium. It also means that light thus injected into the material will have an
enhanced interaction time with particles contained within the material. These
results show that, by using the multiple scattering of light in a turbid medium,
enhanced light-matter interaction can be achieved; this has a direct impact on
spectroscopic methods such as Raman scattering and fluorescence detection in
highly scattering regimes. Furthermore, the enhanced penetration depth achieved
by this method will directly impact optical techniques that have previously been
limited by the inability to deposit sufficient amounts of optical energy below or
through highly scattering layers.
PMID- 28701382
TI - Reduced orbitofrontal cortical volume is associated with interdependent self
construal.
AB - Interdependent self-construal refers to a view of the self as embedded in
relationships with others. Prior work suggests that this construal is linked to a
strong value placed on social obligations and duties. Interdependent people are
therefore cognitively attuned to others and various social events in their
surroundings while down-regulating their personal goals. In the present work, we
examined whether structural properties of the brain predict interdependent self
construal. We performed a structural magnetic resonance imaging on 135 Japanese
young adults while assessing (i) independent and interdependent self-construals
and (ii) the degree to which individuals form vivid images of external objects
(object imagery). The cortical volume of the orbitofrontal cortex (OFC) (a core
cortical region responsible for value-based decisionmaking and, thus, inherently
involved in personal goals and desires) inversely predicted interdependent self
construal. Further analysis found that the highest level of interdependent self
construal is achieved when those who are relatively low in the OFC volume are
simultaneously high in object imagery, consistent with previous evidence that
interdependence, as realized via obligation and duty, requires both the reduced
self-interest and vigilant cognitive attunement to environmental context.
PMID- 28701383
TI - Reply to Arlaud et al.: Structure of the C1 complex and the unbound C1r2s2
tetramer.
PMID- 28701384
TI - Structure of the C1 complex of complement.
PMID- 28701385
TI - Biotin: From Nutrition to Therapeutics.
AB - Although frank symptomatic biotin deficiency is rare, some evidence suggests that
marginal biotin deficiency occurs spontaneously in a substantial proportion of
women during normal human pregnancy and might confer an increased risk of birth
defects. Herein I review 1) advances in assessing biotin status, including the
relation between acylcarnitine excretion and biotin status; 2) recent studies of
biotin status in pregnancy; 3) advances in understanding the role of biotin in
gene expression and the potential roles of biotinylated proteins that are neither
histones nor carboxylases; and 4) novel large-dose biotin supplementation as
therapy for multiple sclerosis. The review concludes with a summary of recent
studies that have reported potentially dangerous erroneous results in individuals
consuming large amounts of biotin for measurements of various plasma hormones for
common clinical assays that use streptavidin-biotin technology.
PMID- 28701386
TI - Low Calcium Intake in Midpregnancy Is Associated with Hypertension Development
within 10 Years after Pregnancy: The Norwegian Mother and Child Cohort Study.
AB - Background: Low dietary calcium intake may be a risk factor for hypertension, but
studies conflict.Objective: We evaluated the ability to predict hypertension
within 10 y after delivery based on calcium intake during midpregnancy.Methods:
The Norwegian Mother and Child Cohort Study of women delivering in 2004-2009 was
linked to the Norwegian Prescription Database (2004-2013) to ascertain
antihypertensive medication usage >90 d after delivery. Women with hypertension
before pregnancy were excluded, leaving 60,027 mothers for analyses. Age and
energy-adjusted cubic splines evaluated dose-response curves, and Cox
proportional hazard analyses evaluated HR and 95% CIs by calcium quartiles
adjusting for 7 covariates. Analyses were stratified by gestational hypertension
and by sodium-to-potassium intake ratio (<0.76 compared with >=0.76).Results:
Participants had a mean +/- SD age of 30.5 +/- 4.6 y, a body mass index (in
kg/m2) of 24.0 +/- 4.3 before pregnancy, and a mean follow-up duration of 7.1 +/-
1.6 y. Cubic spline graphs identified a threshold effect of low calcium intake
only within the range of dietary inadequacy related to increased risk. The lowest
calcium quartile (<=738 mg/d; median: 588 mg/d), relative to the highest quartile
(>=1254 mg/d), had an HR for hypertension of 1.34 (95% CI: 1.05, 1.70) among
women who were normotensive during pregnancy, and an HR of 1.62 (95% CI: 1.14,
2.35) among women who had gestational hypertension, after adjusting for
covariates. Women with gestational hypertension, who were in the lowest quartile
of calcium intake, and who had a high sodium-to-potassium intake ratio had a risk
of hypertension more than double that of their counterparts with a calcium intake
in the highest quartile. Results were attenuated by adjusting for covariates (HR:
1.92; 95% CI: 1.09, 3.39).Conclusions: The results suggest that low dietary
calcium intake may be a risk factor or risk marker for the development of
hypertension, particularly for women with a history of gestational hypertension.
PMID- 28701387
TI - High Iron Stores in the Low Malaria Season Increase Malaria Risk in the High
Transmission Season in a Prospective Cohort of Rural Zambian Children.
AB - Background: Higher iron stores, defined by serum ferritin (SF) concentration, may
increase malaria risk.Objective: We evaluated the association between SF assessed
during low malaria season and the risk of malaria during high malaria season,
controlling for inflammation.Methods: Data for this prospective study were
collected from children aged 4-8 y (n = 745) participating in a biofortified
maize efficacy trial in rural Zambia. All malaria cases were treated at baseline
(September 2012). We used baseline SF and malaria status indicated by positive
microscopy at endline (March 2013) to define exposure and outcome, respectively.
Iron status was defined as deficient (corrected or uncorrected SF <12 or <15
MUg/L, depending on age <5 or >=5 y, respectively), moderate (<75 MUg/L,
excluding deficient), or high (>=75 MUg/L). We used a modified Poisson regression
to model the risk of malaria in the high transmission seasons (endline) as a
function of iron status assessed in the low malaria seasons (baseline).Results:
We observed an age-dependent, positive dose-response association between ferritin
in the low malaria season and malaria incidence during the high malaria season in
younger children. In children aged <6 y (but not older children), we observed a
relative increase in malaria risk in the moderate iron status [incidence rate
ratio (IRR) with SF: 1.56; 95% CI: 0.64, 3.86; IRR with inflammation-corrected
SF: 1.92; 95% CI: 0.75, 4.93] and high iron status (IRR with SF: 2.66; 95% CI:
1.10, 6.43; or IRR with corrected SF: 2.93; 95% CI: 1.17, 7.33) categories
compared with the deficient iron status category. The relative increase in
malaria risk for children with high iron status was statistically significant
only among those with a concurrently normal serum soluble transferrin receptor
concentration (<8.3 mg/L; IRR: 1.97; 95% CI: 1.20, 7.37).Conclusions: Iron
adequacy in 4- to 8-y-old children in rural Zambia was associated with increased
malaria risk. Our findings underscore the need to integrate iron interventions
with malaria control programs. This trial was registered at clinicaltrials.gov as
NCT01695148.
PMID- 28701388
TI - Should We Restrict Vitamin A Intake, a Minor Contributor to Plasma Retinol
Turnover, When Using Retinol Isotope Dilution Equations to Estimate an
Individual's Vitamin A Status, or Should Vitamin A Balance Be Maintained?
AB - We discuss whether dietary vitamin A intake should be restricted or maintained at
balance when retinol isotope dilution equations are applied to estimate an
individual's vitamin A total body stores (TBS) after oral administration of a
labeled dose of vitamin A. Although, at first glance, restriction makes sense as
a way to prevent dilution of tracer in plasma, further investigation of the
assumptions underlying the widely used isotope dilution equation presented by
Olson's laboratory in 1989, as well as the compartmental modeling results
presented in this article, indicate that, in fact, restriction leads to an
incorrect prediction of TBS if steady state retinol isotope dilution equations
are applied at the traditional time (21 d). Our results show that newly ingested
vitamin A is a minor contributor to total plasma retinol turnover and that
restriction of vitamin A intake leads to a higher plasma retinol specific
activity than the value obtained when vitamin A input equals output (balance).
When that higher specific activity is used in the traditional retinol isotope
dilution equation, it results in a small but notable underestimation of vitamin A
TBS. We conclude that, especially if blood is sampled at the traditional time,
the most accurate results will be obtained when vitamin A balance is maintained.
If sampling is done soon after dosing (e.g., 4 d), dietary intake has less effect
on plasma retinol specific activity and thus on predictions of vitamin A status.
Vitamin A status can also be estimated if intake is completely restricted and a
different (non-steady state) equation is applied at an appropriate time after
isotopic equilibrium has been reached.
PMID- 28701389
TI - Meal Frequency and Timing Are Associated with Changes in Body Mass Index in
Adventist Health Study 2.
AB - Background: Scientific evidence for the optimal number, timing, and size of meals
is lacking.Objective: We investigated the relation between meal frequency and
timing and changes in body mass index (BMI) in the Adventist Health Study 2 (AHS
2), a relatively healthy North American cohort.Methods: The analysis used data
from 50,660 adult members aged >=30 y of Seventh-day Adventist churches in the
United States and Canada (mean +/- SD follow-up: 7.42 +/- 1.23 y). The number of
meals per day, length of overnight fast, consumption of breakfast, and timing of
the largest meal were exposure variables. The primary outcome was change in BMI
per year. Linear regression analyses (stratified on baseline BMI) were adjusted
for important demographic and lifestyle factors.Results: Subjects who ate 1 or 2
meals/d had a reduction in BMI per year (in kg . m-2 . y-1) (-0.035; 95% CI:
0.065, -0.004 and -0.029; 95% CI: -0.041, -0.017, respectively) compared with
those who ate 3 meals/d. On the other hand, eating >3 meals/d (snacking) was
associated with a relative increase in BMI (P < 0.001). Correspondingly, the BMI
of subjects who had a long overnight fast (>=18 h) decreased compared with those
who had a medium overnight fast (12-17 h) (P < 0.001). Breakfast eaters (-0.029;
95% CI: -0.047, -0.012; P < 0.001) experienced a decreased BMI compared with
breakfast skippers. Relative to subjects who ate their largest meal at dinner,
those who consumed breakfast as the largest meal experienced a significant
decrease in BMI (-0.038; 95% CI: -0.048, -0.028), and those who consumed a big
lunch experienced a smaller but still significant decrease in BMI than did those
who ate their largest meal at dinner.Conclusions: Our results suggest that in
relatively healthy adults, eating less frequently, no snacking, consuming
breakfast, and eating the largest meal in the morning may be effective methods
for preventing long-term weight gain. Eating breakfast and lunch 5-6 h apart and
making the overnight fast last 18-19 h may be a useful practical strategy.
PMID- 28701390
TI - Spontaneous Closure of Patent Ductus Arteriosus in Infants <=1500 g.
AB - OBJECTIVES: Patent ductus arteriosus (PDA) remains a challenging issue in very
low birth weight (VLBW) infants, and its management varies widely. Our aim in
this study was to document the natural course of ductus arteriosus in a cohort of
VLBW infants who underwent conservative PDA management with no medical or
surgical intervention. METHODS: A retrospective cohort study conducted in 2
European level-3 neonatal units. RESULTS: A total of 368 VLBW infants were born
within the study period. Two hundred and ninety-seven infants were free of
congenital malformations or heart defects and survived to hospital discharge. Out
of those, 280 infants received truly conservative PDA management. In 237 (85%) of
nontreated infants, the PDA closed before hospital discharge. The Kaplan-Meier
model was used to document the incidence proportion of PDA closure over time for
different gestational age groups. The median time to ductal closure was 71, 13,
8, and 6 days in <26+0, 26+0 to 27+6, 28+0 to 29+6, and >=30 weeks, respectively.
For different birth weight groups, the median was 48, 22, 9, and 8 days in
infants weighing <750, 750 to 999, 1000 to 1249, and 1250 to 1500 g,
respectively. No statistically significant relationship was found between PDA
closure before hospital discharge and neonatal morbidities. CONCLUSIONS: The
likelihood of PDA spontaneous closure in VLBW infants is extremely high. We
provide in our findings a platform for future placebo-controlled trials focused
on the smallest and youngest infants.
PMID- 28701391
TI - Hey, Doctor, Leave the PDA Alone.
PMID- 28701392
TI - Partially Uncleaved Alphavirus Replicase Forms Spherule Structures in the
Presence and Absence of RNA Template.
AB - Alphaviruses are positive-strand RNA viruses expressing their replicase as a
polyprotein, P1234, which is cleaved to four final products, nonstructural
proteins nsP1 to nsP4. The replicase proteins together with viral RNA and host
factors form membrane invaginations termed spherules, which act as the
replication complexes producing progeny RNAs. We have previously shown that the
wild-type alphavirus replicase requires a functional RNA template and active
polymerase to generate spherule structures. However, we now find that specific
partially processed forms of the replicase proteins alone can give rise to
membrane invaginations in the absence of RNA or replication. The minimal
requirement for spherule formation was the expression of properly cleaved nsP4,
together with either uncleaved P123 or with the combination of nsP1 and uncleaved
P23. These inactive spherules were morphologically less regular than replication
induced spherules. In the presence of template, nsP1 plus uncleaved P23 plus nsP4
could efficiently assemble active replication spherules producing both negative
sense and positive-sense RNA strands. P23 alone did not have membrane affinity,
but could be recruited to membrane sites in the presence of nsP1 and nsP4. These
results define the set of viral components required for alphavirus replication
complex assembly and suggest the possibility that it could be reconstituted from
separately expressed nonstructural proteins.IMPORTANCE All positive-strand RNA
viruses extensively modify host cell membranes to serve as efficient platforms
for viral RNA replication. Alphaviruses and several other groups induce
protective membrane invaginations (spherules) as their genome factories. Most
positive-strand viruses produce their replicase as a polyprotein precursor, which
is further processed through precise and regulated cleavages. We show here that
specific cleavage intermediates of the alphavirus replicase can give rise to
spherule structures in the absence of viral RNA. In the presence of template RNA,
the same intermediates yield active replication complexes. Thus, partially
cleaved replicase proteins play key roles that connect replication complex
assembly, membrane deformation, and the different stages of RNA synthesis.
PMID- 28701393
TI - HIV-1 Env- and Vpu-Specific Antibody-Dependent Cellular Cytotoxicity Responses
Associated with Elite Control of HIV.
AB - Studying HIV-infected individuals who control HIV replication (elite controllers
[ECs]) enables exploration of effective anti-HIV immunity. HIV Env-specific and
non-Env-specific antibody-dependent cellular cytotoxicity (ADCC) may contribute
to protection from progressive HIV infection, but the evidence is limited. We
recruited 22 ECs and matched them with 44 viremic subjects. HIV Env- and Vpu
specific ADCC responses in sera were studied using a novel enzyme-linked
immunosorbent assay (ELISA)-based dimeric recombinant soluble FcgammaRIIIa
(rsFcgammaRIIIa)-binding assay, surface plasmon resonance, antibody-dependent
natural killer (NK) cell activation assays, and ADCC-mediated killing assays. ECs
had higher levels of HIV Env-specific antibodies capable of binding FcgammaRIIIa,
activating NK cells, and mediating granzyme B activity (all P < 0.01) than
viremic subjects. ECs also had higher levels of antibodies against a C-terminal
13-mer Vpu peptide capable of mediating FcgammaRIIIa binding and NK cell
activation than viremic subjects (both P < 0.05). Our data associate Env-specific
and Vpu epitope-specific ADCC in effective immune responses against HIV among
ECs. Our findings have implications for understanding the role of ADCC in HIV
control.IMPORTANCE Understanding immune responses associated with elite control
of HIV may aid the development of immunotherapeutic and vaccine strategies for
controlling HIV infection. Env is a major HIV protein target of functional
antibody responses that are heightened in ECs. Interestingly, EC antibodies also
target Vpu, an accessory protein crucial to HIV, which degrades CD4 and
antagonizes tetherin. Antibodies specific to Vpu are a common feature of the
immune response of ECs that may prove to be of functional importance to the
design of improved ADCC-based immunotherapy and preventative HIV vaccines.
PMID- 28701394
TI - Single-particle detection of transcription following rotavirus entry.
AB - Infectious rotavirus particles are triple-layered, icosahedral assemblies. The
outer layer proteins, VP4 (cleaved to VP8* and VP5*) and VP7, surround a
transcriptionally competent, double-layer particle (DLP), which they deliver into
the cytosol. During entry of rhesus rotavirus, VP8* interacts with cell-surface
gangliosides, allowing engulfment into a membrane vesicle by a clathrin
independent process. Escape into the cytosol and outer-layer shedding depend on
interaction of a hydrophobic surface on VP5* with the membrane bilayer and on a
large-scale conformational change. We report here experiments that detect the
fate of released DLPs and their efficiency in initiating RNA synthesis. By
replacing the outer layer with fluorescently tagged, recombinant proteins and
also tagging the DLP, we distinguish particles that have lost their outer layer
and entered the cytosol (uncoated) from those still within membrane vesicles. We
used fluorescent in situ hybridization with probes for nascent transcripts to
determine how soon after uncoating transcription began and what fraction of the
uncoated particles were active in initiating RNA synthesis. We detected RNA
synthesis by uncoated particles as early as 15 minutes after adding virus.
Uncoating efficiency was 20-50%; of the uncoated particles, about 10% synthesized
detectable RNA. In the format of our experiments, about 1% of the added particles
attached to the cell surface, giving an overall added-particle to RNA
synthesizing particle ratio of between 1000 and 5000 to 1, in good agreement with
the particle-to-focus-forming unit determined by infectivity assays. Thus, RNA
synthesis by even a single, uncoated particle can initiate infection in a
cell.IMPORTANCE The pathways by which a virus enters a cell transform its
packaged genome into an active one. Contemporary fluorescence microscopy can
detect individual virus particles as they enter cells, allowing us to map their
multi-step entry pathways. Rotaviruses, like most viruses that lack membranes of
their own, disrupt or perforate the intracellular, membrane-enclosed compartment
into which they become engulfed following attachment to a cell surface, in order
to gain access to the cell interior. The properties of rotavirus particles make
it possible to determine molecular mechanisms for these entry steps. In the work
described here, we have asked the following question: what fraction of the
rotavirus particles that penetrate into the cell make new viral RNA? We find that
of the cell-attached particles, between 20 and 50% ultimately penetrate, and of
these, about 10% make RNA. RNA synthesis by even a single virus particle can
initiate a productive infection.
PMID- 28701395
TI - Preferential Targeting of Conserved Gag Regions after Vaccination with a
Heterologous DNA Prime-Modified Vaccinia Virus Ankara Boost HIV-1 Vaccine
Regimen.
AB - Prime-boost vaccination strategies against HIV-1 often include multiple variants
for a given immunogen for better coverage of the extensive viral diversity. To
study the immunologic effects of this approach, we characterized breadth,
phenotype, function, and specificity of Gag-specific T cells induced by a DNA
prime modified vaccinia virus Ankara (MVA)-boost vaccination strategy, which uses
mismatched Gag immunogens in the TamoVac 01 phase IIa trial. Healthy Tanzanian
volunteers received three injections of the DNA-SMI vaccine encoding a subtype B
and AB-recombinant Gagp37 and two vaccinations with MVA-CMDR encoding subtype A
Gagp55 Gag-specific T-cell responses were studied in 42 vaccinees using fresh
peripheral blood mononuclear cells. After the first MVA-CMDR boost, vaccine
induced gamma interferon-positive (IFN-gamma+) Gag-specific T-cell responses were
dominated by CD4+ T cells (P < 0.001 compared to CD8+ T cells) that coexpressed
interleukin-2 (IL-2) (66.4%) and/or tumor necrosis factor alpha (TNF-alpha)
(63.7%). A median of 3 antigenic regions were targeted with a higher-magnitude
median response to Gagp24 regions, more conserved between prime and boost,
compared to those of regions within Gagp15 (not primed) and Gagp17 (less
conserved; P < 0.0001 for both). Four regions within Gagp24 each were targeted by
45% to 74% of vaccinees upon restimulation with DNA-SMI-Gag matched peptides. The
response rate to individual antigenic regions correlated with the sequence
homology between the MVA- and DNA Gag-encoded immunogens (P = 0.04, r2 = 0.47).
In summary, after the first MVA-CMDR boost, the sequence-mismatched DNA-prime MVA
boost vaccine strategy induced a Gag-specific T-cell response that was dominated
by polyfunctional CD4+ T cells and that targeted multiple antigenic regions
within the conserved Gagp24 protein.IMPORTANCE Genetic diversity is a major
challenge for the design of vaccines against variable viruses. While including
multiple variants for a given immunogen in prime-boost vaccination strategies is
one approach that aims to improve coverage for global virus variants, the
immunologic consequences of this strategy have been poorly defined so far. It is
unclear whether inclusion of multiple variants in prime-boost vaccination
strategies improves recognition of variant viruses by T cells and by which
mechanisms this would be achieved, either by improved cross-recognition of
multiple variants for a given antigenic region or through preferential targeting
of antigenic regions more conserved between prime and boost. Engineering vaccines
to induce adaptive immune responses that preferentially target conserved
antigenic regions of viral vulnerability might facilitate better immune control
after preventive and therapeutic vaccination for HIV and for other variable
viruses.
PMID- 28701396
TI - Effects of the NEDD8-Activating Enzyme Inhibitor MLN4924 on Lytic Reactivation of
Kaposi's Sarcoma-Associated Herpesvirus.
AB - The switch of Kaposi's sarcoma-associated herpesvirus (KSHV) from latency to
lytic replication is a key event for viral dissemination and pathogenesis.
MLN4924, a novel neddylation inhibitor, reportedly causes the onset of KSHV
reactivation but impairs later phases of the viral lytic program in infected
cells. Thus far, the molecular mechanism involved in the modulation of the KSHV
lytic cycle by MLN4924 is not yet fully understood. Here, we confirmed that
treatment of different KSHV-infected primary effusion lymphoma (PEL) cell lines
with MLN4924 substantially induces viral lytic protein expression. Due to the key
role of the virally encoded ORF50 protein in the latent-to-lytic switch, we
investigated its transcriptional regulation by MLN4924. We found that MLN4924
activates the ORF50 promoter (ORF50p) in KSHV-positive cells (but not in KSHV
negative cells), and the RBP-Jkappa-binding elements within the promoter are
critically required for MLN4924 responsiveness. In KSHV-negative cells,
reactivation of the ORF50 promoter by MLN4924 requires the presence of the
latency-associated nuclear antigen (LANA). Under such a condition, LANA acts as a
repressor to block the ORF50p activity, whereas MLN4924 treatment relieves LANA
mediated repression. Importantly, we showed that LANA is a neddylated protein and
can be deneddylated by MLN4924. On the other hand, we revealed that MLN4924
exhibits concentration-dependent biphasic effects on 12-O-tetradecanoylphorbol-13
acetate (TPA)- or sodium butyrate (SB)-induced viral reactivation in PEL cell
lines. In other words, low concentrations of MLN4924 promote activation of TPA-
or SB-mediated viral reactivation, whereas high concentrations of MLN4924,
conversely, inhibit the progression of TPA- or SB-mediated viral lytic
program.IMPORTANCE MLN4924 is a neddylation (NEDD8 modification) inhibitor, which
currently acts as an anti-cancer drug in clinical trials. Although MLN4924 has
been reported to trigger KSHV reactivation, many aspects regarding the action of
MLN4924 in regulating the KSHV lytic cycle are not fully understood. Since the
KSHV ORF50 protein is the key regulator of viral lytic reactivation, we focus on
its transcriptional regulation by MLN4924. We here show that activation of the
ORF50 gene by MLN4924 involves the relief of LANA-mediated transcriptional
repression. Importantly, we find that LANA is a neddylated protein. To our
knowledge, this is the first report showing that neddylation occurs in viral
proteins. Additionally, we provide evidence that different concentrations of
MLN4924 have opposite effects on TPA-mediated or SB-mediated KSHV lytic cycle
activation. Therefore, in clinical application, we propose that MLN4924 needs to
be used with caution in combination therapy to treat KSHV-positive subjects.
PMID- 28701397
TI - B Cell-Specific Expression of Ataxia-Telangiectasia Mutated Protein Kinase
Promotes Chronic Gammaherpesvirus Infection.
AB - Manipulation of host cellular pathways is a strategy employed by
gammaherpesviruses, including mouse gammaherpesvirus 68 (MHV68), in order to
negotiate a chronic infection. Ataxia-telangiectasia mutated (ATM) plays a unique
yet incompletely understood role in gammaherpesvirus infection, as it has both
proviral and antiviral effects. Chronic gammaherpesvirus infection is poorly
controlled in a host with global ATM insufficiency, whether the host is a mouse
or a human. In contrast, ATM facilitates replication, reactivation, and latency
establishment of several gammaherpesviruses in vitro, suggesting that ATM is
proviral in the context of infected cell cultures. The proviral role of ATM is
also evident in vivo, as myeloid-specific ATM expression facilitates MHV68
reactivation during the establishment of viral latency. In order to better
understand the complex relationship between host ATM and gammaherpesvirus
infection, we depleted ATM specifically in B cells, a cell type critical for
chronic gammaherpesvirus infection. B cell-specific ATM deficiency attenuated the
establishment of viral latency due to compromised differentiation of ATM
deficient B cells. Further, we found that during long-term infection, peritoneal
B-1b, but not related B-1a, B cells display the highest frequency of
gammaherpesvirus infection. While ATM expression did not affect gammaherpesvirus
tropism for B-1 B cells, B cell-specific ATM expression was necessary to support
viral reactivation from peritoneal cells during long-term infection. Thus, our
study reveals a role of ATM as a host factor that promotes chronic
gammaherpesvirus infection of B cells.IMPORTANCE Gammaherpesviruses infect a
majority of the human population and are associated with cancer, including B cell
lymphomas. ATM is a unique host kinase that has both proviral and antiviral roles
in the context of gammaherpesvirus infection. Further, there is insufficient
understanding of the interplay of these roles in vivo during chronic infection.
In this study, we show that ATM expression by splenic B cells is required for
efficient establishment of gammaherpesvirus latency. We also show that ATM
expression by peritoneal B cells is required to facilitate viral reactivation
during long-term infection. Thus, our study defines a proviral role of B cell
specific ATM expression during chronic gammaherpesvirus infection.
PMID- 28701398
TI - Protection against HIV Acquisition in the RV144 Trial.
AB - Differences of opinion regarding whether there may, or may not, have been
protective efficacy in the RV144 vaccine trial have important societal
implications.
PMID- 28701399
TI - Selective Expression of CCR10 and CXCR3 by Circulating Human Herpes Simplex Virus
Specific CD8 T Cells.
AB - Herpes simplex virus (HSV) infection is restricted to epithelial cells and
neurons and is controlled by CD8 T cells. These cells both traffic to epithelial
sites of recurrent lytic infection and to ganglia and persist at the dermal
epidermal junction for up to 12 weeks after lesion resolution. We previously
showed that cutaneous lymphocyte-associated antigen (CLA), a functional E
selectin ligand (ESL), is selectively expressed on circulating HSV-2-specific CD8
T cells. CLA/ESL mediates adhesion of T cells to inflamed vascular endothelium.
Later stages in T-cell homing involve chemokines (Ch) and lymphocyte chemokine
receptors (ChR) for vascular wall arrest and diapedesis. Several candidate ChR
have been implicated in skin homing. We measured cell surface ChR on HSV-specific
human peripheral blood CD8 T cells and extended our studies to HSV-1. We observed
preferential cell surface expression of CCR10 and CXCR3 by HSV-specific CD8 T
cells compared to CD8 T cells specific for control viruses, Epstein-Barr virus
(EBV) and cytomegalovirus (CMV), and compared to bulk memory CD8 T cells. CXCR3
ligand mRNA levels were selectively increased in skin biopsy specimens from
persons with recurrent HSV-2, while the mRNA levels of the CCR10 ligand CCL27
were equivalent in lesion and control skin. Our data are consistent with a model
in which CCL27 drives baseline recruitment of HSV-specific CD8 T cells expressing
CCR10, while interferon-responsive CXCR3 ligands recruit additional cells in
response to virus-driven inflammation.IMPORTANCE HSV-2 causes very localized
recurrent infections in the skin and genital mucosa. Virus-specific CD8 T cells
home to the site of recurrent infection and participate in viral clearance. The
exit of T cells from the blood involves the use of chemokine receptors on the T
cell surface and chemokines that are present in infected tissue. In this study,
circulating HSV-2-specific CD8 T cells were identified using specific fluorescent
tetramer reagents, and their expression of several candidate skin-homing
associated chemokine receptors was measured using flow cytometry. We found that
two chemokine receptors, CXCR3 and CCR10, are upregulated on HSV-specific CD8 T
cells in blood. The chemokines corresponding to these receptors are also
expressed in infected tissues. Vaccine strategies to prime CD8 T cells to home to
HSV lesions should elicit these chemokine receptors if possible to increase the
homing of vaccine-primed cells to sites of infection.
PMID- 28701400
TI - Whole-Genome Sequencing and Variant Analysis of Human Papillomavirus 16
Infections.
AB - Human papillomavirus (HPV) is a strongly conserved DNA virus, high-risk types of
which can cause cervical cancer in persistent infections. The most common type
found in HPV-attributable cancer is HPV16, which can be subdivided into four
lineages (A to D) with different carcinogenic properties. Studies have shown
HPV16 sequence diversity in different geographical areas, but only limited
information is available regarding HPV16 diversity within a population,
especially at the whole-genome level. We analyzed HPV16 major variant diversity
and conservation in persistent infections and performed a single nucleotide
polymorphism (SNP) comparison between persistent and clearing infections.
Materials were obtained in the Netherlands from a cohort study with longitudinal
follow-up for up to 3 years. Our analysis shows a remarkably large variant
diversity in the population. Whole-genome sequences were obtained for 57
persistent and 59 clearing HPV16 infections, resulting in 109 unique variants.
Interestingly, persistent infections were completely conserved through time. One
reinfection event was identified where the initial and follow-up samples
clustered differently. Non-A1/A2 variants seemed to clear preferentially (P =
0.02). Our analysis shows that population-wide HPV16 sequence diversity is very
large. In persistent infections, the HPV16 sequence was fully conserved.
Sequencing can identify HPV16 reinfections, although occurrence is rare. SNP
comparison identified no strongly acting effect of the viral genome affecting
HPV16 infection clearance or persistence in up to 3 years of follow-up. These
findings suggest the progression of an early HPV16 infection could be host
related.IMPORTANCE Human papillomavirus 16 (HPV16) is the predominant type found
in cervical cancer. Progression of initial infection to cervical cancer has been
linked to sequence properties; however, knowledge of variants circulating in
European populations, especially with longitudinal follow-up, is limited. By
sequencing a number of infections with known follow-up for up to 3 years, we
gained initial insights into the genetic diversity of HPV16 and the effects of
the viral genome on the persistence of infections. A SNP comparison between
sequences obtained from clearing and persistent infections did not identify
strongly acting DNA variations responsible for these infection outcomes. In
addition, we identified an HPV16 reinfection event where sequencing of initial
and follow-up samples showed different HPV16 variants. Based on conventional
genotyping, this infection would incorrectly be considered a persistent HPV16
infection. In the context of vaccine efficacy and monitoring studies, such
infections could potentially cause reduced reported efficacy or efficiency.
PMID- 28701401
TI - Evaluation of the biological properties and cross-reactive antibody response to
H10 influenza viruses in ferrets.
AB - The recent outbreak of avian origin H10N7 influenza among seals in Northern
Europe, and two fatal human infections with an avian H10N8 virus in China, have
demonstrated that H10 viruses can spread between mammals and cause severe disease
in humans. To gain insight into the potential for H10 viruses to cross the
species barrier and identify a candidate vaccine strain, we evaluated the in
vitro and in vivo properties and antibody response in ferrets to 20 diverse H10
viruses. H10 virus infection of ferrets caused variable weight loss and all 20
viruses replicated throughout the respiratory tract; however, replication in the
lungs was highly variable. In glycan-binding assays, the H10 viruses
preferentially bound "avian-like" alpha2,3-linked sialic acids. Importantly,
several isolates also displayed strong binding to long-chain "human-like"
alpha2,6-linked sialic acids, and exhibited comparable or elevated neuraminidase
activity relative to human H1N1, H2N2, and H3N2 viruses. In hemagglutination
inhibition assays, 12 antisera cross-reacted with >= 14 of 20 H10 viruses, and 7
viruses induced neutralizing activity against >= 15 of the 20 viruses. By
combining data on weight loss, viral replication, and the cross-reactive antibody
response, we identified A/mallard/Portugal/79906/2009 (H10N7) as a suitable virus
for vaccine development. Collectively, our findings suggest that H10 viruses may
continue to sporadically infect humans and other mammals, underscoring the
importance of developing an H10 vaccine for pandemic preparedness.IMPORTANCE
Avian origin H10 influenza viruses sporadically infect humans and other mammals;
however, little is known about viruses of this subtype. Thus, we characterized
the biological properties of 20 H10 viruses in vitro and in ferrets. Infection
caused mild to moderate weight loss (5-15%), with robust viral replication in the
nasal tissues and variable replication in the lung. H10 viruses preferentially
bind "avian-like" sialic acids, although several isolates also displayed binding
to "human-like" sialic acid receptors. This is consistent with the ability of H10
viruses to cross the species barrier, and warrants selection of an H10 vaccine
strain. By evaluating the cross-reactive antibody response to the H10 viruses,
and combining this analysis with viral replication and weight loss findings, we
identified A/mallard/Portugal/79906/2009 (H10N7) as a suitable H10 vaccine
strain.
PMID- 28701402
TI - Increased, Durable B-Cell and ADCC Responses Associated with T-Helper Cell
Responses to HIV-1 Envelope in Macaques Vaccinated with gp140 Occluded at the CD4
Receptor Binding Site.
AB - Strategies are needed to improve the immunogenicity of HIV-1 envelope (Env)
antigens (Ag) for more long-lived, efficacious HIV-1 vaccine-induced B-cell
responses. HIV-1 Env gp140 (native or uncleaved molecules) or gp120 monomeric
proteins elicit relatively poor B-cell responses which are short-lived. We
hypothesized that Env engagement of the CD4 receptor on T-helper cells results in
anergic effects on T-cell recruitment and consequently a lack of strong, robust,
and durable B-memory responses. To test this hypothesis, we occluded the CD4
binding site (CD4bs) of gp140 by stable cross-linking with a 3-kDa CD4
miniprotein mimetic, serving to block ligation of gp140 on CD4+ T cells while
preserving CD4-inducible (CDi) neutralizing epitopes targeted by antibody
dependent cellular cytotoxicity (ADCC) effector responses. Importantly,
immunization of rhesus macaques consistently gave superior B-cell (P < 0.001)
response kinetics and superior ADCC (P < 0.014) in a group receiving the CD4bs
occluded vaccine compared to those of animals immunized with gp140. Of the
cytokines examined, Ag-specific interleukin-4 (IL-4) T-helper enzyme-linked
immunosorbent spot (ELISpot) assays of the CD4bs-occluded group increased earlier
(P = 0.025) during the inductive phase. Importantly, CD4bs-occluded gp140 antigen
induced superior B-cell and ADCC responses, and the elevated B-cell responses
proved to be remarkably durable, lasting more than 60 weeks
postimmunization.IMPORTANCE Attempts to develop HIV vaccines capable of inducing
potent and durable B-cell responses have been unsuccessful until now. Antigen
specific B-cell development and affinity maturation occurs in germinal centers in
lymphoid follicles through a critical interaction between B cells and T
follicular helper cells. The HIV envelope binds the CD4 receptor on T cells as
soluble shed antigen or as antigen-antibody complexes, causing impairment in the
activation of these specialized CD4-positive T cells. We proposed that CD4
binding impairment is partly responsible for the relatively poor B-cell responses
to HIV envelope-based vaccines. To test this hypothesis, we blocked the CD4
binding site of the envelope antigen and compared it to currently used unblocked
envelope protein. We found superior and durable B-cell responses in macaques
vaccinated with an occluded CD4 binding site on the HIV envelope antigen,
demonstrating a potentially important new direction in future design of new HIV
vaccines.
PMID- 28701403
TI - Monoclonal Antibodies, Derived from Humans Vaccinated with the RV144 HIV Vaccine
Containing the HVEM Binding Domain of Herpes Simplex Virus (HSV) Glycoprotein D,
Neutralize HSV Infection, Mediate Antibody-Dependent Cellular Cytotoxicity, and
Protect Mice from Ocular Challenge with HSV-1.
AB - The RV144 HIV vaccine trial included a recombinant HIV glycoprotein 120 (gp120)
construct fused to a small portion of herpes simplex virus 1 (HSV-1) glycoprotein
D (gD) so that the first 40 amino acids of gp120 were replaced by the signal
sequence and the first 27 amino acids of the mature form of gD. This region of gD
contains most of the binding site for HVEM, an HSV receptor important for virus
infection of epithelial cells and lymphocytes. RV144 induced antibodies to HIV
that were partially protective against infection, as well as antibodies to HSV.
We derived monoclonal antibodies (MAbs) from peripheral blood B cells of
recipients of the RV144 HIV vaccine and showed that these antibodies neutralized
HSV-1 infection in cells expressing HVEM, but not the other major virus receptor,
nectin-1. The MAbs mediated antibody-dependent cellular cytotoxicity (ADCC), and
mice that received the MAbs and were then challenged by corneal inoculation with
HSV-1 had reduced eye disease, shedding, and latent infection. To our knowledge,
this is the first description of MAbs derived from human recipients of a vaccine
that specifically target the HVEM binding site of gD. In summary, we found that
monoclonal antibodies derived from humans vaccinated with the HVEM binding domain
of HSV-1 gD (i) neutralized HSV-1 infection in a cell receptor-specific manner,
(ii) mediated ADCC, and (iii) reduced ocular disease in virus-infected
mice.IMPORTANCE Herpes simplex virus 1 (HSV-1) causes cold sores and neonatal
herpes and is a leading cause of blindness. Despite many trials, no HSV vaccine
has been approved. Nectin-1 and HVEM are the two major cellular receptors for
HSV. These receptors are expressed at different levels in various tissues, and
the role of each receptor in HSV pathogenesis is not well understood. We derived
human monoclonal antibodies from persons who received the HIV RV144 vaccine that
contained the HVEM binding domain of HSV-1 gD fused to HIV gp120. These
antibodies were able to specifically neutralize HSV-1 infection in vitro via
HVEM. Furthermore, we showed for the first time that HVEM-specific HSV-1
neutralizing antibodies protect mice from HSV-1 eye disease, indicating the
critical role of HVEM in HSV-1 ocular infection.
PMID- 28701404
TI - Enterovirus 3A facilitates viral replication by promoting PI4KB-ACBD3
interaction.
AB - Like other enteroviruses, EV71 relies on phosphatidylinositol-4-kinase IIIbeta
(PI4KB) for genome RNA replication. However, how PI4KB is recruited to the genome
replication sites of EV71 remains elusive. Recently, we reported that a host
factor ACBD3 is needed for EV71 replication by interacting with viral 3A protein.
Here, we show that ACBD3 is required for the recruitment of PI4KB to RNA
replication sites. Overexpression of viral 3A or EV71 infection stimulates the
interaction of PI4KB and ACBD3. Consistently, EV71 infection induces the
production of phosphatidylinositol-4-phosphate (PI4P). Furthermore, PI4KB, ACBD3
and 3A are all localized to the viral RNA replication sites. Accordingly, PI4KB
or ACBD3 depletion by siRNA leads to a reduction in the PI4P production after
EV71 infection. I44A or H54Y substitution in 3A interrupts the stimulation of
PI4KB and ACBD3. Further analysis suggests that stimulation of ACBD3-PI4KB
interaction is also important for the replication of enterovirus 68 but
disadvantageous to human rhinovirus 16. These results reveal a mechanism of
enterovirus replication that involves a selective strategy for recruitment of
PI4KB to the RNA replication sites.IMPORTANCE Enterovirus 71, like other human
enteroviruses, replicates its genome within host cells, where viral proteins
efficiently utilize cellular machineries. While multiple factors are involved, it
is largely unclear how viral replication is controlled. We show that the 3A
protein of enterovirus 71 recruits an enzyme phosphatidylinositol-4-kinase
IIIbeta by interacting with ACBD3, which alter cellular membranes through the
production of a lipid PI4P. Consequently, the viral and host proteins form a
large complex that is necessary for RNA synthesis at replication sites. Notably,
PI4KB-ACBD3 interaction also differentially mediates the replication of
enterovirus 68 and rhinovirus 16. These results provide a new insight into the
molecular network of enterovirus replication.
PMID- 28701405
TI - Propagation of astrovirus VA1, a neurotropic human astrovirus, in cell culture.
AB - Astrovirus VA1/HMO-C (VA1; mamastrovirus 9) is a recently discovered astrovirus
genotype that is divergent from the classic human astroviruses (mamastrovirus 1).
The gastrointestinal tract is presumed to be the primary site of infection and
pathogenicity for astroviruses. However, VA1 has been independently detected in
brain tissue of five cases of human encephalitis. Studies of the pathogenicity of
VA1 are currently impossible because there are no reported cell culture systems
or in vivo models that support VA1 infection. Here, we describe successful
propagation of VA1 in multiple human cell lines. The initial inoculum, a filtered
clinical stool sample from the index gastroenteritis case cluster that lead to
discovery of VA1, was first passaged in Vero cells. Serial blind passage in Caco
2 yielded increasing copies of VA1 RNA and multi-step growth curves demonstrated
a greater than 100-fold increase in VA1 RNA 72 hours after inoculation. The full
length genomic and subgenomic RNA strands were detected by Northern blotting, and
crystalline lattices of viral particles of ~ 26 nm diameter were observed by
electron microscopy in infected Caco-2 cells. Unlike other human astrovirus cell
culture systems which require addition of exogenous trypsin for continued
propagation, VA1 could be propagated equally well with or without the addition of
trypsin. Furthermore, VA1 was sensitive to the type I interferon response as VA1
RNA levels were reduced by pre-treatment of Caco-2 cells with interferon-beta1a.
The ability to propagate VA1 in cell culture will facilitate studies of the
neurotropism and neuropathogenesis of VA1.IMPORTANCE Astroviruses are an emerging
cause of central nervous system infections in mammals, and astrovirus VA1/HMO-C
is the most prevalent astrovirus in cases of human encephalitis. This virus has
not been previously propagated, preventing elucidation of the biology of this
virus. We describe the first cell culture system for VA1, a key step necessary
for the study of its ability to cause disease.
PMID- 28701406
TI - Structural and Functional Basis for an EBNA1 Hexameric Ring in Epstein-Barr Virus
Episome Maintenance.
AB - Epstein-Barr virus (EBV) establishes a stable latent infection that can persist
for the life of the host. EBNA1 is required for the replication, maintenance, and
segregation of the latent episome, but the structural features of EBNA1 that
confer each of these functions are not completely understood. Here, we have
solved the X-ray crystal structure of an EBNA1 DNA-binding domain (DBD) and
discovered a novel hexameric ring oligomeric form. The oligomeric interface
pivoted around residue T585 as a joint that links and stabilizes higher-order
EBNA1 complexes. Substitution mutations around the interface destabilized higher
order complex formation and altered the cooperative DNA-binding properties of
EBNA1. Mutations had both positive and negative effects on EBNA1-dependent DNA
replication and episome maintenance with OriP. We found that one naturally
occurring polymorphism in the oligomer interface (T585P) had greater cooperative
DNA binding in vitro, minor defects in DNA replication, and pronounced defects in
episome maintenance. The T585P mutant was compromised for binding to OriP in vivo
as well as for assembling the origin recognition complex subunit 2 (ORC2) and
trimethylated histone 3 lysine 4 (H3K4me3) at OriP. The T585P mutant was also
compromised for forming stable subnuclear foci in living cells. These findings
reveal a novel oligomeric structure of EBNA1 with an interface subject to
naturally occurring polymorphisms that modulate EBNA1 functional properties. We
propose that EBNA1 dimers can assemble into higher-order oligomeric structures
important for diverse functions of EBNA1.IMPORTANCE Epstein-Barr virus is a human
gammaherpesvirus that is causally associated with various cancers. Carcinogenic
properties are linked to the ability of the virus to persist in the latent form
for the lifetime of the host. EBNA1 is a sequence-specific DNA-binding protein
that is consistently expressed in EBV tumors and is the only viral protein
required to maintain the viral episome during latency. The structural and
biochemical mechanisms by which EBNA1 allows the long-term persistence of the EBV
genome are currently unclear. Here, we have solved the crystal structure of an
EBNA1 hexameric ring and characterized key residues in the interface required for
higher-order complex formation and long-term plasmid maintenance.
PMID- 28701408
TI - Digital medical humanities: stage-to-screen lessons from a five year initiative.
PMID- 28701407
TI - Experimental Transmission of the Chronic Wasting Disease Agent to Swine after
Oral or Intracranial Inoculation.
AB - Chronic wasting disease (CWD) is a naturally occurring, fatal neurodegenerative
disease of cervids. The potential for swine to serve as hosts for the agent of
CWD is unknown. The purpose of this study was to investigate the susceptibility
of swine to the CWD agent following experimental oral or intracranial
inoculation. Crossbred piglets were assigned to three groups, intracranially
inoculated (n = 20), orally inoculated (n = 19), and noninoculated (n = 9). At
approximately the age at which commercial pigs reach market weight, half of the
pigs in each group were culled ("market weight" groups). The remaining pigs
("aged" groups) were allowed to incubate for up to 73 months postinoculation
(mpi). Tissues collected at necropsy were examined for disease-associated prion
protein (PrPSc) by Western blotting (WB), antigen capture enzyme immunoassay
(EIA), immunohistochemistry (IHC), and in vitro real-time quaking-induced
conversion (RT-QuIC). Brain samples from selected pigs were also bioassayed in
mice expressing porcine prion protein. Four intracranially inoculated aged pigs
and one orally inoculated aged pig were positive by EIA, IHC, and/or WB. By RT
QuIC, PrPSc was detected in lymphoid and/or brain tissue from one or more pigs in
each inoculated group. The bioassay was positive in four out of five pigs
assayed. This study demonstrates that pigs can support low-level amplification of
CWD prions, although the species barrier to CWD infection is relatively high.
However, detection of infectivity in orally inoculated pigs with a mouse bioassay
raises the possibility that naturally exposed pigs could act as a reservoir of
CWD infectivity.IMPORTANCE We challenged domestic swine with the chronic wasting
disease agent by inoculation directly into the brain (intracranially) or by oral
gavage (orally). Disease-associated prion protein (PrPSc) was detected in brain
and lymphoid tissues from intracranially and orally inoculated pigs as early as 8
months of age (6 months postinoculation). Only one pig developed clinical
neurologic signs suggestive of prion disease. The amount of PrPSc in the brains
and lymphoid tissues of positive pigs was small, especially in orally inoculated
pigs. Regardless, positive results obtained with orally inoculated pigs suggest
that it may be possible for swine to serve as a reservoir for prion disease under
natural conditions.
PMID- 28701409
TI - What outcomes are associated with developing and implementing co-produced
interventions in acute healthcare settings? A rapid evidence synthesis.
AB - BACKGROUND: Co-production is defined as the voluntary or involuntary involvement
of users in the design, management, delivery and/or evaluation of services.
Interest in co-production as an intervention for improving healthcare quality is
increasing. In the acute healthcare context, co-production is promoted as
harnessing the knowledge of patients, carers and staff to make changes about
which they care most. However, little is known regarding the impact of co
production on patient, staff or organisational outcomes in these settings. AIMS:
To identify and appraise reported outcomes of co-production as an intervention to
improve quality of services in acute healthcare settings. DESIGN: Rapid evidence
synthesis. DATA SOURCES: Medline, Cinahl, Web of Science, Embase, HMIC, Cochrane
Database of Systematic Reviews, SCIE, Proquest Dissertation and Theses, EThOS,
OpenGrey; CoDesign; The Design Journal; Design Issues. STUDY SELECTION: Studies
reporting patient, staff or organisational outcomes associated with using co
production in an acute healthcare setting. FINDINGS: 712 titles and abstracts
were screened; 24 papers underwent full-text review, and 11 papers were included
in the evidence synthesis. One study was a feasibility randomised controlled
trial, three were process evaluations and seven used descriptive qualitative
approaches. Reported outcomes related to (a) the value of patient and staff
involvement in co-production processes; (b) the generation of ideas for changes
to processes, practices and clinical environments; and (c) tangible service
changes and impacts on patient experiences. Only one study included cost
analysis; none reported an economic evaluation. No studies assessed the
sustainability of any changes made. CONCLUSIONS: Despite increasing interest in
and advocacy for co-production, there is a lack of rigorous evaluation in acute
healthcare settings. Future studies should evaluate clinical and service outcomes
as well as the cost-effectiveness of co-production relative to other forms of
quality improvement. Potentially broader impacts on the values and behaviours of
participants should also be considered.
PMID- 28701410
TI - Maternal alcohol use disorder and child school attendance outcomes for non
Indigenous and Indigenous children in Western Australia: a population cohort
record linkage study.
AB - OBJECTIVES: Examine the relationship between maternal alcohol use disorder and
child school attendance outcomes for non-Indigenous and Indigenous children in
Western Australia. DESIGN: Population cohort study. SETTING: Routinely collected
linked administrative health, education and child protection data. PARTICIPANTS:
Those in-scope for the study were women with a birth recorded on the Western
Australian Midwives Notification System (1989-2007). Women who had an alcohol
related diagnosis (International Classification of Diseases Revisions 9/10)
recorded on the Hospital Morbidity, Mental Health Inpatients and Outpatients, and
Drug and Alcohol Office data sets formed the exposed group. The comparison cohort
was frequency-matched to the exposed cohort based on maternal age within
Indigenous status and child's year of birth. PRIMARY OUTCOME MEASURE: Child's
school attendance was obtained from the Department of Education (2008-2012). Poor
attendance was defined as <80% attendance for non-Indigenous children and <60%
attendance for Indigenous children. RESULTS: 11 430 exposed children and 26 850
unexposed children had a linked attendance record. Maternal alcohol use disorder
was significantly associated with increased odds of poor attendance (non
Indigenous: OR=1.61, 95% CI 1.50 to 1.74; Indigenous: OR=1.66, 95% CI 1.54 to
1.79). With adjustment for maternal and child factors, there was no significant
difference between the timing of alcohol diagnosis relative to pregnancy and
attendance outcomes. The population attributable fraction was higher in the
Indigenous cohort than the non-Indigenous cohort (6.0% vs 1.3%). CONCLUSIONS:
Maternal alcohol use disorder was associated with a significantly increased odds
of poor school attendance for non-Indigenous and Indigenous children. There was
no significant difference between the timing of diagnoses and odds of poor school
attendance. This suggests that the effect of maternal alcohol use disorder may
not be driven by the neurodevelopmental effects of alcohol exposure in utero, but
may be mediated through family or social factors for which we were unable to
adjust.
PMID- 28701411
TI - What determines treatment satisfaction of patients with type 2 diabetes on
insulin therapy? An observational study in eight European countries.
AB - OBJECTIVE: Patients with type 2 diabetes (T2DM) on insulin therapy are less
satisfied with their diabetes treatment than those on oral hypoglycaemic
therapies or lifestyle advice only. Determinants of satisfaction in patients with
T2DM on insulin therapy are not clearly known. The aim of this study was to
determine the association of treatment satisfaction with demographic and clinical
characteristics of patients with T2DM. DESIGN: For this study we used data from
the GUIDANCE (Guideline Adherence to Enhance Care) study, a cross-sectional study
among 7597 patients with T2DM patients from Belgium, France, Germany, Ireland,
Italy, Sweden, the Netherlands and the UK. The majority of patients were
recruited from primary care. Treatment satisfaction was assessed by the Diabetes
Treatment Satisfaction Questionnaire (DTSQ, score 0-36; higher scores reflecting
higher satisfaction). To determine which patient characteristics and laboratory
values were independently associated with treatment satisfaction, a linear mixed
model analysis was used. PARTICIPANTS: In total, 1984 patients on insulin were
analysed; the number of included patients per country ranged from 166 (the
Netherlands) to 384 (Italy). RESULTS: The mean DTSQ score was 28.50+/-7.52 and
ranged from 25.93+/-6.57 (France) to 30.11+/-5.09 (the Netherlands). Higher DTSQ
scores were associated with having received diabetes education (beta 1.64, 95% CI
0.95 to 2.32), presence of macrovascular complications (beta 0.76, 95% CI 0.21 to
1.31) and better health status (beta 0.08 for every one unit increase on a 0-100
scale, 95% CI 0.07 to 0.10). Lower DTSQ scores were associated with more
frequently perceived hyperglycaemia (beta -0.32 for every 1 unit increase on a
seven-point Likert scale, 95% CI -0.50 to -0.13), and higher glycated haemoglobin
(beta -0.52 for every percentage increase, 95% CI -0.75 to -0.29). CONCLUSIONS: A
number of factors including diabetes education, perceived and actual
hyperglycaemia and macrovascular complications are associated with treatment
satisfaction. Self-management education programmes should incorporate these
factors for ongoing support in patients with T2DM.
PMID- 28701412
TI - The effect of blinding on estimates of mortality in randomised clinical trials of
intensive care interventions: protocol for a systematic review and meta-analysis.
AB - INTRODUCTION: Evidence exists that unblinded randomised clinical trials (RCTs)
overestimate intervention effects compared with blinded RCTs. It has been
suggested that this is less pronounced for objective (ie, not subject to
interpretation) outcome measures, including mortality. This may not apply in the
intensive care unit (ICU), as most deaths are preceded by decisions to withhold
or withdraw treatments. Lack of blinding of physicians in RCTs of ICU
interventions may potentially influence the decision towards a higher threshold
for discontinuing treatment in patients who receive the investigational treatment
and/or a lower threshold for discontinuing treatment in patients who receive the
comparator (control). This may have important implications for patients,
caregivers, researchers and society. Accordingly, we aim to assess whether lack
of blinding affects mortality effect estimates in RCTs of ICU interventions.
METHODS AND ANALYSIS: We will conduct a systematic review with meta-analyses and
assess the effect of blinding versus no blinding on mortality effect estimates in
RCTs of interventions used in adult ICU patients.We will systematically search
the Cochrane Library for systematic reviews reporting mortality effect estimates
of any intervention used in adult ICU patients which includes at least one RCT
with 'low risk of bias' in the bias domains 'blinding of participants and
personnel' and/or 'blinding of outcome assessment' and one RCT with 'unclear' or
'high risk of bias' in the same bias domain(s). For each intervention, we will
compare summary mortality effect estimates in blinded versus unblinded trials.
ETHICS AND DISSEMINATION: This research does not require ethical approval as we
will use summary data from trials already approved by relevant ethical
institutions. We will report the results in accordance with the Preferred
Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statement and
submit the final paper to an international peer-reviewed journal. TRIAL
REGISTRATION NUMBER: PROSPERO, registration number: CRD42017056212.
PMID- 28701414
TI - Correction: A realist review to explore how low-income pregnant women use food
vouchers from the UK's Healthy Start programme.
PMID- 28701413
TI - A directly comparative two-gate case-control diagnostic accuracy study of the
pure tone screen and HearCheck screener tests for identifying hearing impairment
in school children.
AB - OBJECTIVES: This study directly compared the accuracy of two audiometry-based
tests for screening school children for hearing impairment: the currently used
test, pure tone screen and a device newly applied to children, HearCheck
Screener. DESIGN: Two-gate case-control diagnostic test accuracy study. SETTING
AND PARTICIPANTS: Hearing impaired children ('intended cases') aged 4-6 years
were recruited between February 2013 and August 2014 from collaborating audiology
services. Children with no previously identified impairment ('intended controls')
were recruited from Foundation and Year 1 of schools between February 2013 and
June 2014 in central England. The reference standard was pure tone audiometry.
Tests were administered at Nottingham Hearing Biomedical Research Unit or, for
some intended cases only, in the participant's home. MAIN OUTCOME MEASURES:
Sensitivity and specificity of the pure tone screen and HearCheck tests based on
pure tone audiometry result as reference standard. RESULTS: 315 children (630
ears) were recruited; 75 from audiology services and 240 from schools. Full test
and reference standard data were obtained for 600 ears; 155 ears were classified
as truly impaired and 445 as truly hearing based on the pure tone audiometry
assessment. Sensitivity was estimated to be 94.2% (95% CI 89.0% to 97.0%) for
pure tone screen and 89.0% (95% CI 82.9% to 93.1%) for HearCheck (difference=5.2%
favouring pure tone screen; 95% CI 0.2% to 10.1%; p=0.02). Estimates for
specificity were 82.2% (95% CI 77.7% to 86.0%) for pure tone screen and 86.5%
(95% CI 82.5% to 89.8%) for HearCheck (difference=4.3% favouring HearCheck; 95%
CI0.4% to 8.2%; p=0.02). CONCLUSION: Pure tone screen was better than HearCheck
with respect to sensitivity but inferior with respect to specificity. As avoiding
missed cases is arguably of greater importance for school entry screening, pure
tone screen is probably preferable in this context. STUDY REGISTRATION NUMBER:
Current controlled trials: ISRCTN61668996.
PMID- 28701415
TI - Structure of the PSD-95/MAP1A complex reveals a unique target recognition mode of
the MAGUK GK domain.
AB - The PSD-95 family of membrane-associated guanylate kinases (MAGUKs) are major
synaptic scaffold proteins and play crucial roles in the dynamic regulation of
dendritic remodelling, which is understood to be the foundation of synaptogenesis
and synaptic plasticity. The guanylate kinase (GK) domain of MAGUK family
proteins functions as a phosphor-peptide binding module. However, the GK domain
of PSD-95 has been found to directly bind to a peptide sequence within the C
terminal region of neuronal-specific microtubule-associated protein 1A (MAP1A),
although the detailed molecular mechanism governing this phosphorylation
independent interaction at the atomic level is missing. In the present study, we
determine the crystal structure of PSD-95 GK in complex with the MAP1A peptide at
2.6-A resolution. The complex structure reveals that, unlike a linear and
elongated conformation in the phosphor-peptide/GK complexes, the MAP1A peptide
adopts a unique conformation with a stretch of hydrophobic residues far from each
other in the primary sequence clustering and interacting with the 'hydrophobic
site' of PSD-95 GK and a highly conserved aspartic acid of MAP1A (D2117)
mimicking the phosphor-serine/threonine in binding to the 'phosphor-site' of PSD
95 GK. We demonstrate that the MAP1A peptide may undergo a conformational
transition upon binding to PSD-95 GK. Further structural comparison of known DLG
GK-mediated complexes reveals the target recognition specificity and versatility
of DLG GKs.
PMID- 28701416
TI - Eukaryotic transcription factors: paradigms of protein intrinsic disorder.
AB - Gene-specific transcription factors (TFs) are key regulatory components of
signaling pathways, controlling, for example, cell growth, development, and
stress responses. Their biological functions are determined by their molecular
structures, as exemplified by their structured DNA-binding domains targeting
specific cis-acting elements in genes, and by the significant lack of fixed
tertiary structure in their extensive intrinsically disordered regions. Recent
research in protein intrinsic disorder (ID) has changed our understanding of
transcriptional activation domains from 'negative noodles' to ID regions with
function-related, short sequence motifs and molecular recognition features with
structural propensities. This review focuses on molecular aspects of TFs, which
represent paradigms of ID-related features. Through specific examples, we review
how the ID-associated flexibility of TFs enables them to participate in large
interactomes, how they use only a few hydrophobic residues, short sequence
motifs, prestructured motifs, and coupled folding and binding for their
interactions with co-activators, and how their accessibility to post
translational modification affects their interactions. It is furthermore
emphasized how classic biochemical concepts like allostery, conformational
selection, induced fit, and feedback regulation are undergoing a revival with the
appreciation of ID. The review also describes the most recent advances based on
computational simulations of ID-based interaction mechanisms and structural
analysis of ID in the context of full-length TFs and suggests future directions
for research in TF ID.
PMID- 28701417
TI - Protein trafficking in the mitochondrial intermembrane space: mechanisms and
links to human disease.
AB - Mitochondria fulfill a diverse range of functions in cells including oxygen
metabolism, homeostasis of inorganic ions and execution of apoptosis. Biogenesis
of mitochondria relies on protein import pathways that are ensured by dedicated
multiprotein translocase complexes localized in all sub-compartments of these
organelles. The key components and pathways involved in protein targeting and
assembly have been characterized in great detail over the last three decades.
This includes the oxidative folding machinery in the intermembrane space, which
contributes to the redox-dependent control of proteostasis. Here, we focus on
several components of this system and discuss recent evidence suggesting links to
human proteopathy.
PMID- 28701418
TI - Laboratory Workflow Analysis of Culture of Periprosthetic Tissues in Blood
Culture Bottles.
AB - Culture of periprosthetic tissue specimens in blood culture bottles is more
sensitive than conventional techniques, but the impact on laboratory workflow has
yet to be addressed. Herein, we examined the impact of culture of periprosthetic
tissues in blood culture bottles on laboratory workflow and cost. The workflow
was process mapped, decision tree models were constructed using probabilities of
positive and negative cultures drawn from our published study (T. N. Peel, B. L.
Dylla, J. G. Hughes, D. T. Lynch, K. E. Greenwood-Quaintance, A. C. Cheng, J. N.
Mandrekar, and R. Patel, mBio 7:e01776-15, 2016,
https://doi.org/10.1128/mBio.01776-15), and the processing times and resource
costs from the laboratory staff time viewpoint were used to compare
periprosthetic tissues culture processes using conventional techniques with
culture in blood culture bottles. Sensitivity analysis was performed using
various rates of positive cultures. Annualized labor savings were estimated based
on salary costs from the U.S. Labor Bureau for Laboratory staff. The model
demonstrated a 60.1% reduction in mean total staff time with the adoption of
tissue inoculation into blood culture bottles compared to conventional techniques
(mean +/- standard deviation, 30.7 +/- 27.6 versus 77.0 +/- 35.3 h per month,
respectively; P < 0.001). The estimated annualized labor cost savings of culture
using blood culture bottles was $10,876.83 (+/-$337.16). Sensitivity analysis was
performed using various rates of culture positivity (5 to 50%). Culture in blood
culture bottles was cost-effective, based on the estimated labor cost savings of
$2,132.71 for each percent increase in test accuracy. In conclusion, culture of
periprosthetic tissue in blood culture bottles is not only more accurate than but
is also cost-saving compared to conventional culture methods.
PMID- 28701419
TI - Proviral Features of Human T Cell Leukemia Virus Type 1 in Carriers with
Indeterminate Western Blot Analysis Results.
AB - Western blotting (WB) for human T cell leukemia virus type 1 (HTLV-1) is
performed to confirm anti-HTLV-1 antibodies detected at the initial screening of
blood donors and in pregnant women. However, the frequent occurrence of
indeterminate results is a problem with this test. We therefore assessed the
cause of indeterminate WB results by analyzing HTLV-1 provirus genomic sequences.
A quantitative PCR assay measuring HTLV-1 provirus in WB-indeterminate samples
revealed that the median proviral load was approximately 100-fold lower than that
of WB-positive samples (0.01 versus 0.71 copy/100 cells). Phylogenic analysis of
the complete HTLV-1 genomes of WB-indeterminate samples did not identify any
specific phylogenetic groups. When we analyzed the nucleotide changes in 19 HTLV
1 isolates from WB-indeterminate samples, we identified 135 single nucleotide
substitutions, composed of four types, G to A (29%), C to T (19%), T to C (19%),
and A to G (16%). In the most frequent G-to-A substitution, 64% occurred at GG
dinucleotides, indicating that APOBEC3G is responsible for mutagenesis in WB
indeterminate samples. Moreover, interestingly, five WB-indeterminate isolates
had nonsense mutations in Pol and/or Tax, Env, p12, and p30. These findings
suggest that WB-indeterminate carriers have low production of viral antigens
because of a combination of a low proviral load and mutations in the provirus,
which may interfere with host recognition of HTLV-1 antigens.
PMID- 28701421
TI - Carbapenemase Detection among Carbapenem-Resistant Glucose-Nonfermenting Gram
Negative Bacilli.
AB - Accurate detection of carbapenemase-producing glucose-nonfermenting Gram-negative
bacilli (CPNFs), including Pseudomonas aeruginosa and Acinetobacter baumannii, is
necessary to prevent their dissemination within health care settings. We
performed a method comparison study of 11 phenotypic carbapenemase detection
assays to evaluate their accuracy for the detection of CPNFs. A total of 96
carbapenem-resistant glucose-nonfermenting isolates were included, of which 29%
produced carbapenemases. All CPNFs were molecularly characterized to identify
beta-lactamase genes. A total of 86% of the carbapenemase-producing P. aeruginosa
isolates produced class B carbapenemases. Several assays performed with a
sensitivity of >90% for the detection of carbapenemase-producing P. aeruginosa,
including all rapid chromogenic assays and the modified carbapenem inactivation
method. Most included assays, with the exception of the Manual Blue Carba assay,
the Modified Carba NP assay, the boronic acid synergy test, and the metallo-beta
lactamase Etest, had specificities of >90% for detecting carbapenemase-producing
P. aeruginosa Class D carbapenemases were the most prevalent carbapenemases among
the carbapenemase-producing A. baumannii strains, with 60% of the carbapenemase
producing A. baumannii isolates producing acquired OXA-type carbapenemases.
Although several assays achieved >90% specificity in identifying carbapenemase
producing A. baumannii, no assays achieved a sensitivity of greater than 90%. Our
findings suggest that the available phenotypic tests generally appear to have
excellent sensitivity and specificity for detecting carbapenemase-producing P.
aeruginosa isolates. However, further modifications to existing assays or novel
assays may be necessary to accurately detect carbapenemase-producing A.
baumannii.
PMID- 28701420
TI - Comparative Evaluation of Subtyping Tools for Surveillance of Newly Emerging HIV
1 Strains.
AB - HIV-1 non-B subtypes/circulating recombinant forms (CRFs) are increasing
worldwide. Since subtype identification can be clinically relevant, we assessed
the added value in HIV-1 subtyping using updated molecular phylogeny (Mphy) and
the performance of routinely used automated tools. Updated Mphy (2015 updated
reference sequences), used as a gold standard, was performed to subtype 13,116
HIV-1 protease/reverse transcriptase sequences and then compared with previous
Mphy (reference sequences until 2014) and with COMET, REGA, SCUEAL, and Stanford
subtyping tools. Updated Mphy classified subtype B as the most prevalent (73.4%),
followed by CRF02_AG (7.9%), C (4.6%), F1 (3.4%), A1 (2.2%), G (1.6%), CRF12_BF
(1.2%), and other subtypes (5.7%). A 2.3% proportion of sequences were reassigned
as different subtypes or CRFs because of misclassification by previous Mphy.
Overall, the tool most concordant with updated Mphy was Stanford-v8.1 (95.4%),
followed by COMET (93.8%), REGA-v3 (92.5%), Stanford-old (91.1%), and SCUEAL
(85.9%). All the tools had a high sensitivity (>=98.0%) and specificity (>=95.7%)
for subtype B. Regarding non-B subtypes, Stanford-v8.1 was the best tool for C,
D, and F subtypes and for CRFs 01, 02, 06, 11, and 36 (sensitivity, >=92.6%;
specificity, >=99.1%). A1 and G subtypes were better classified by COMET (92.3%)
and REGA-v3 (98.6%), respectively. Our findings confirm Mphy as the gold standard
for accurate HIV-1 subtyping, although Stanford-v8.1, occasionally combined with
COMET or REGA-v3, represents an effective subtyping approach in clinical
settings. Periodic updating of HIV-1 reference sequences is fundamental to
improving subtype characterization in the context of an effective epidemiological
surveillance of non-B strains.
PMID- 28701423
TI - Harvey Marcovitch: Editor, poacher, gamekeeper.
PMID- 28701422
TI - New Highly Sensitive Real-Time PCR Assay for HIV-2 Group A and Group B DNA
Quantification.
AB - HIV-2 infection is characterized by a very low replication rate in most cases and
low progression. This necessitates an approach to patient monitoring that differs
from that for HIV-1 infection. Here, a new highly specific and sensitive method
for HIV-2 DNA quantification was developed. The new test is based on quantitative
real-time PCR targeting the long terminal repeat (LTR) and gag regions and using
an internal control. Analytical performance was determined in three laboratories,
and clinical performance was determined on blood samples from 63 patients
infected with HIV-2 group A (n = 35) or group B (n = 28). The specificity was
100%. The 95% limit of detection was three copies/PCR and the limit of
quantification was six copies/PCR. The within-run coefficients of variation were
between 1.03% at 3.78 log10 copies/PCR and 27.02% at 0.78 log10 copies/PCR. The
between-run coefficient of variation was 5.10%. Both manual and automated nucleic
acid extraction methods were validated. HIV-2 DNA loads were detectable in blood
cells from all 63 patients. When HIV-2 DNA was quantifiable, median loads were
significantly higher in antiretroviral-treated than in naive patients and were
similar for groups A and B. HIV-2 DNA load was correlated with HIV-2 RNA load (r
= 0.68; 95% confidence interval [CI], 0.4 to 0.8; P < 0.0001). Our data show that
this new assay is highly sensitive and quantifies the two main HIV-2 groups,
making it useful for the diagnosis of HIV-2 infection and for pathogenesis
studies on HIV-2 reservoirs.
PMID- 28701424
TI - More than a mere supply of monomers: G-Actin pools regulate actin dynamics in
dendritic spines.
AB - Synaptic activity reshapes the morphology of dendritic spines via regulating F
actin arborization. In this issue, Lei et al. (2017. J. Cell Biol.
https://doi.org/10.1083/jcb.201612042) reports a novel, G-actin-dependent
regulation of actin polymerization within spine heads. They show that actin
monomer levels are elevated in spines upon activity, with G-actin immobilized by
the local enrichment of phosphatidylinositol (3,4,5)-triphosphate (PIP3) within
the spine plasma membrane.
PMID- 28701425
TI - Self-sorting of nonmuscle myosins IIA and IIB polarizes the cytoskeleton and
modulates cell motility.
AB - Nonmuscle myosin II (NMII) is uniquely responsible for cell contractility and
thus defines multiple aspects of cell behavior. To generate contraction, NMII
molecules polymerize into bipolar minifilaments. Different NMII paralogs are
often coexpressed in cells and can copolymerize, suggesting that they may
cooperate to facilitate cell motility. However, whether such cooperation exists
and how it may work remain unknown. We show that copolymerization of NMIIA and
NMIIB followed by their differential turnover leads to self-sorting of NMIIA and
NMIIB along the front-rear axis, thus producing a polarized actin-NMII
cytoskeleton. Stress fibers newly formed near the leading edge are enriched in
NMIIA, but over time, they become progressively enriched with NMIIB because of
faster NMIIA turnover. In combination with retrograde flow, this process results
in posterior accumulation of more stable NMIIB-rich stress fibers, thus
strengthening cell polarity. By copolymerizing with NMIIB, NMIIA accelerates the
intrinsically slow NMIIB dynamics, thus increasing cell motility and traction and
enabling chemotaxis.
PMID- 28701426
TI - Dynamics of in vivo ASC speck formation.
AB - Activated danger or pathogen sensors trigger assembly of the inflammasome adaptor
ASC into specks, large signaling platforms considered hallmarks of inflammasome
activation. Because a lack of in vivo tools has prevented the study of endogenous
ASC dynamics, we generated a live ASC reporter through CRISPR/Cas9 tagging of the
endogenous gene in zebrafish. We see strong ASC expression in the skin and other
epithelia that act as barriers to insult. A toxic stimulus triggered speck
formation and rapid pyroptosis in keratinocytes in vivo. Macrophages engulfed and
digested that speck-containing, pyroptotic debris. A three-dimensional,
ultrastructural reconstruction, based on correlative light and electron
microscopy of the in vivo assembled specks revealed a compact network of highly
intercrossed filaments, whereas pyrin domain (PYD) or caspase activation and
recruitment domain alone formed filamentous aggregates. The effector caspase is
recruited through PYD, whose overexpression induced pyroptosis but only after
substantial delay. Therefore, formation of a single, compact speck and rapid cell
death induction in vivo requires a full-length ASC.
PMID- 28701427
TI - Controlling Phlebotomy Volume Diminishes PICU Transfusion: Implementation
Processes and Impact.
AB - BACKGROUND AND OBJECTIVES: Phlebotomy excess contributes to anemia in PICU
patients and increases the likelihood of red blood cell transfusion, which is
associated with risk of adverse outcomes. Excessive phlebotomy reduction (EPR)
strategies may reduce the need for transfusion, but have not been evaluated in a
PICU population. We hypothesized that EPR strategies, facilitated by
implementation science methods, would decrease excess blood drawn and reduce
transfusion frequency. METHODS: Quantitative and qualitative methods were used.
Patient and blood draw data were collected with survey and focus group data to
evaluate knowledge and attitudes before and after EPR intervention. The
Consolidated Framework for Implementation Research was used to interpret
qualitative data. Multivariate regression was employed to adjust for potential
confounders for blood overdraw volume and transfusion incidence. RESULTS:
Populations were similar pre- and postintervention. EPR strategies decreased
blood overdraw volumes 62% from 5.5 mL (interquartile range 1-23) preintervention
to 2.1 mL (interquartile range 0-7.9 mL) postintervention (P < .001). Fewer
patients received red blood cell transfusions postintervention (32.1%
preintervention versus 20.7% postintervention, P = .04). Regression analyses
showed that EPR strategies reduced blood overdraw volume (P < .001) and lowered
transfusion frequency (P = .05). Postintervention surveys reflected a high degree
of satisfaction (93%) with EPR strategies, and 97% agreed EPR was a priority
postintervention. CONCLUSIONS: Implementation science methods aided in the
selection of EPR strategies and enhanced acceptance which, in this cohort,
reduced excessive overdraw volumes and transfusion frequency. Larger trials are
needed to determine if this approach can be applied in broader PICU populations.
PMID- 28701428
TI - A Mercury Toxicity Case Complicated by Hyponatremia and Abnormal Endocrinological
Test Results.
AB - Mercury (Hg) poisoning is considered a rare disease by the National Institutes of
Health and the diagnosis can present great challenges to clinicians. Children who
are exposed to Hg can present with a wide variety of symptoms, including
acrodynia, tremor, excessive salivation, and psychiatric symptoms, including
insomnia. However, endocrinologic manifestations from Hg exposure are less well
known. This is a case report of a 12-year-old boy who presented with body rash,
irritability, insomnia, and profuse sweating after returning from a summer camp.
The child was initially managed in the outpatient setting, and the investigation
was mainly targeted toward infectious etiology, including Rocky Mountain spotted
fever and Lyme disease. He was eventually admitted to the hospital with altered
mental status and was noted to have hyponatremia with serum sodium of 121 mEq/L.
Thyroid studies also revealed elevated free thyroxine levels in the presence of
normal triiodothyronine and thyrotropin. The patient developed hypertension and
tachycardia, and was found to have elevated 24-hour vanillylmandelic acid and
metanephrines. Finally, heavy metal measurements revealed a blood Hg level that
was greater than the reference values of 0 to 9 ng/mL. Chelation treatment with
2,3-dimercaptopropane-1-sulfonate was subsequently initiated and over a period of
8 months his symptoms resolved and his thyroid function test returned to normal.
This case highlights some of the challenges commonly encountered in identifying
Hg exposure. More importantly, it illustrates that exposure to Hg should be
considered in children who present with the symptoms and abnormal endocrinologic
test results described in this report.
PMID- 28701429
TI - Endovascular interventions for acute stroke: past practice and current research.
PMID- 28701430
TI - Patients, not pictures: why complete occlusion may be a complete disaster.
PMID- 28701431
TI - Holding a wolf by the ears: Preventive care and the family physician.
PMID- 28701433
TI - Implementing preventive health care recommendations in family medicine:
Introducing a series from the Canadian Task Force on Preventive Health Care.
PMID- 28701434
TI - The 5 As framework for obesity management: Do we need a more intricate model?
PMID- 28701435
TI - Opioid agonist therapy.
PMID- 28701436
TI - Hospitalists reduce harm and improve care for hospitalized patients.
PMID- 28701437
TI - Correction.
PMID- 28701438
TI - Community-associated methicillin-resistant Staphylococcus aureus infection:
Literature review and clinical update.
AB - OBJECTIVE: To provide information on the prevalence and treatment of methicillin
resistant Staphylococcus aureus (MRSA) infections and the distinction between
community-associated MRSA and health care-associated MRSA. QUALITY OF EVIDENCE:
The MEDLINE and EMBASE databases were searched from 2005 to 2016. Epidemiologic
studies were summarized and the relevant treatment literature was based on level
I evidence. MAIN MESSAGE: The incidence of community-associated MRSA infection is
rising. Certain populations, including indigenous Canadians and homeless
populations, are particularly affected. Community-associated MRSA can be
distinguished from health care-associated MRSA based on genetic, epidemiologic,
or microbiological profiles. It retains susceptibility to some oral agents
including trimethoprim-sulfamethoxazole, clindamycin, and tetracyclines.
Community-associated MRSA typically presents as purulent skin and soft tissue
infection, but invasive infection occurs and can lead to severe, complicated
disease. Treatment choices and the need for empiric MRSA coverage are influenced
by the type and severity of infection. CONCLUSION: Community-associated MRSA is a
common cause of skin and soft tissue infections and might be common in
populations where overcrowding and limited access to clean water exist.
PMID- 28701439
TI - Better decision making in preventive health screening: Balancing benefits and
harms.
PMID- 28701441
TI - Topiramate for pediatric migraine prevention.
AB - Question I have several teenagers in my clinic with migraine headache and some of
them have frequent episodes that cause considerable interference with daily
activity. I would like to offer them prophylactic therapy to reduce the frequency
of their migraine episodes. Is topiramate an effective and safe option for
adolescents? Answer Both Health Canada and the US Food and Drug Administration
have approved the use of topiramate for migraine prevention in adults; however,
only the US Food and Drug Administration has approved topiramate for migraine
prophylaxis in adolescents 12 to 17 years of age. Although several studies
support its effectiveness in preventing migraine, most of these studies are
small; and a recent large multicentre, randomized placebo-controlled trial was
stopped early when no benefit was shown over placebo. Adverse effects of
topiramate are mild and typically resolve over time. The recommended dosage is 2
mg/kg per day, up to an adult dose of 100 mg/d.
PMID- 28701443
TI - Critical elevation of international normalized ratio in an elderly woman using a
natural health product.
PMID- 28701445
TI - Choosing Wisely Canada recommendations.
PMID- 28701446
TI - Improving the clinical care of Indigenous peoples.
PMID- 28701447
TI - What is urgent about hypertensive urgency?
PMID- 28701448
TI - From beer brewing to vaccine stability: Adding a digital temperature controller
to your vaccine refrigerator.
PMID- 28701450
TI - Old oak tree.
PMID- 28701452
TI - Importance of Certification.
PMID- 28701449
TI - The CHANGE program: Exercise intervention in primary care.
AB - PROBLEM ADDRESSED: Primary care settings require a feasible program for
integrating lifestyle interventions, which can reverse metabolic abnormalities,
for patients in practice. OBJECTIVE OF PROGRAM: To integrate a lifestyle
intervention program into existing primary care clinics with an interprofessional
approach that includes dietitians and kinesiologists. PROGRAM DESCRIPTION:
Canadian Health Advanced by Nutrition and Graded Exercise (CHANGE) provides a
personalized approach to nutrition and exercise modification focusing on patients
with metabolic syndrome. With CHANGE, exercise intervention is individualized
(ie, tailored to individual preferences) and graded (ie, intensity is built up
slowly over time); supervision and implementation of the program is conducted in
a collaborative fashion between the family physician and the kinesiologist.
Patients undergo an initial fitness assessment that determines their baseline
aerobic, strength, and flexibility scores, and the same assessment is performed
at 3 months and at 12 months. CONCLUSION: The CHANGE program demonstrates how
interprofessional primary care teams can support patients with metabolic syndrome
in achieving their health goals. By including dietitians and kinesiologists in
primary care settings to work alongside family doctors, many barriers to
lifestyle interventions can be overcome. The team's collaborative understanding
of the patient combined with the patient's own sense of urgency for change
creates the opportunity for the formation of new healthy lifestyle habits.
Although results are preliminary, CHANGE appears to be a feasible, implementable,
and effective program.
PMID- 28701455
TI - Cautious look at the 2017 CaRMS match results.
PMID- 28701459
TI - Staff perceptions of community health centre team function in Ontario.
AB - OBJECTIVE: To examine perceptions of different staff groups about team
functioning in mature, community-governed, interprofessional primary health care
practices. DESIGN: Cross-sectional online survey. SETTING: The 75 community
health centres (CHCs) in Ontario at the time of the study, which have cared for
people with barriers to access to traditional health services in community
governed, interprofessional settings, providing medical, social, and community
services since the 1970s. PARTICIPANTS: Managers and staff of primary care teams
in the CHCs. MAIN OUTCOME MEASURES: Scores on the short version of the Team
Climate Inventory (with subscales addressing vision, task orientation, support
for innovation, and participative safety), the Organizational Justice Scale (with
subscales addressing procedural justice and interactional justice), and the
Organizational Citizenship Behavior Scale, stratified by staff group (clinical
manager, FP, nurse practitioner [NP], registered nurse, medical secretary, social
worker, allied health provider, counselor, outreach worker, and administrative
assistant). RESULTS: A total of 674 staff members in 58 of 75 (77%) CHCs
completed surveys. All staff groups generally reported positive perceptions of
team function. The procedural justice subscale showed the greatest variation
between groups. Family physicians and NPs rated procedural justice much lower
than nurses and administrators did. CONCLUSION: This study provides a unique view
of the perceptions of different groups of staff in a long-standing
interprofessional practice model. Future research is needed to understand why FPs
and NPs perceive procedural justice more negatively than other team members do,
and whether such perceptions affect outcomes such as staff turnover and health
outcomes for patients.
PMID- 28701460
TI - Clinician self-efficacy in initiating discussions about gestational weight gain.
AB - OBJECTIVE: To compare prenatal care providers' perceived self-efficacy in
starting discussions about gestational weight gain with pregnant women under a
variety of conditions of gradated difficulty, when weight gain has been in excess
of current guidelines. DESIGN: A 42-item online questionnaire related to the
known barriers to and facilitators of having discussions about gestational weight
gain. SETTING: Canada. PARTICIPANTS: Prenatal care providers were contacted
through the Family Medicine Maternity Care list server of the College of Family
Physicians of Canada. MAIN OUTCOME MEASURES: The 42 items were clustered into
categories representing patient factors, interpersonal factors, and system
factors. Participants scored their self-efficacy on a scale from 0 ("cannot do at
all") to 5 ("moderately certain can do") to 10 ("highly certain can do"). The
significance level was set at alpha = .05. RESULTS: Overall, clinicians rated
their self-efficacy to be high, ranging from a low mean (SD) score of 5.14 (3.24)
if the clinic was running late, to a high mean score of 8.97 (1.34) if the
clinician could externalize the reason for undertaking the discussion. There were
significant differences in self-efficacy scores within categories depending on
the degree of difficulty proposed by the items in those categories. CONCLUSION:
The results were inconsistent with previous studies that have demonstrated that
prenatal care providers do not frequently raise the subject of excess gestational
weight gain. On the one hand providers rate their self-efficacy in having these
discussions to be high, but on the other hand they do not undertake the
behaviour, at least according to their patients. Future research should explore
this discrepancy with a view to informing interventions to help providers and
patients in their efforts to address excess gestational weight gain, which is
increasingly an important contributor to the obesity epidemic.
PMID- 28701461
TI - Opioid use disorder and type 2 diabetes mellitus: Effect of participation in
buprenorphine-naloxone substitution programs on glycemic control.
AB - OBJECTIVE: To measure the effect of buprenorphine-naloxone as opioid substitution
therapy on glycemic control in patients with type 2 diabetes mellitus and opioid
use disorder. DESIGN: Retrospective cohort study and secondary data analysis.
SETTING: Northwestern Ontario. PARTICIPANTS: Patients with diabetes receiving
opioid substitution therapy, as well as patients with diabetes only, who live in
6 remote First Nations communities. MAIN OUTCOME MEASURES: Glycated hemoglobin
A1c values during a 2-year time period in the 2 groups. RESULTS: Over a 2-year
period, there was an absolute decrease of 1.20% in mean glycated hemoglobin A1c
values in patients with diabetes who also received opioid substitution therapy,
compared with patients with diabetes who were not being treated for opioid
dependence, whose values rose by 0.02%. CONCLUSION: Patients with diabetes who
also suffer from opioid use disorder achieve significant (P = .011) improvement
in glycemic control when treated with buprenorphine-naloxone substitution therapy
compared with other patients with diabetes. Treating opioid use disorder with
buprenorphine-naloxone substitution therapy has an unintended positive effect on
diabetes management.
PMID- 28701462
TI - ?
PMID- 28701463
TI - Inverted stereocontrol of iridoid synthase in snapdragon.
AB - The natural product class of iridoids, found in various species of flowering
plants, harbors astonishing chemical complexity. The discovery of iridoid
biosynthetic genes in the medicinal plant Catharanthus roseus has provided
insight into the biosynthetic origins of this class of natural product. However,
not all iridoids share the exact five- to six-bicyclic ring scaffold of the
Catharanthus iridoids. For instance, iridoids in the ornamental flower snapdragon
(Antirrhinum majus, Plantaginaceae family) are derived from the C7 epimer of this
scaffold. Here we have cloned and characterized the iridoid synthase enzyme from
A. majus (AmISY), the enzyme that is responsible for converting 8-oxogeranial
into the bicyclic iridoid scaffold in a two-step reduction-cyclization sequence.
Chiral analysis of the reaction products reveals that AmISY reduces C7 to
generate the opposite stereoconfiguration in comparison with the Catharanthus
homologue CrISY. The catalytic activity of AmISY thus explains the biosynthesis
of 7-epi-iridoids in Antirrhinum and related genera. However, although the
stereoselectivity of the reduction step catalyzed by AmISY is clear, in both
AmISY and CrISY, the cyclization step produces a diastereomeric mixture. Although
the reduction of 8-oxogeranial is clearly enzymatically catalyzed, the
cyclization step appears to be subject to less stringent enzyme control.
PMID- 28701464
TI - Human mitochondrial cytochrome P450 27C1 is localized in skin and preferentially
desaturates trans-retinol to 3,4-dehydroretinol.
AB - Recently, zebrafish and human cytochrome P450 (P450) 27C1 enzymes have been shown
to be retinoid 3,4-desaturases. The enzyme is unusual among mammalian P450s in
that the predominant oxidation is a desaturation and in that hydroxylation
represents only a minor pathway. We show by proteomic analysis that P450 27C1 is
localized to human skin, with two proteins of different sizes present, one being
a cleavage product of the full-length form. P450 27C1 oxidized all-trans-retinol
to 3,4-dehydroretinol, 4-hydroxy (OH) retinol, and 3-OH retinol in a 100:3:2
ratio. Neither 3-OH nor 4-OH retinol was an intermediate in desaturation. No
kinetic burst was observed in the steady state; neither the rate of substrate
binding nor product release was rate-limiting. Ferric P450 27C1 reduction by
adrenodoxin was 3-fold faster in the presence of the substrate and was ~5-fold
faster than the overall turnover. Kinetic isotope effects of 1.5-2.3 (on kcat/Km
) were observed with 3,3-, 4,4-, and 3,3,4,4-deuterated retinol. Deuteration at C
4 produced a 4-fold increase in 3-hydroxylation due to metabolic switching, with
no observable effect on 4-hydroxylation. Deuteration at C-3 produced a strong
kinetic isotope effect for 3-hydroxylation but not 4-hydroxylation. Analysis of
the products of deuterated retinol showed a lack of scrambling of a putative
allylic radical at C-3 and C-4. We conclude that the most likely catalytic
mechanism begins with abstraction of a hydrogen atom from C-4 (or possibly C-3)
initiating the desaturation pathway, followed by a sequential abstraction of a
hydrogen atom or proton-coupled electron transfer. Adrenodoxin reduction and
hydrogen abstraction both contribute to rate limitation.
PMID- 28701466
TI - Methionine synthase is localized to the nucleus in Pichia pastoris and Candida
albicans and to the cytoplasm in Saccharomyces cerevisiae.
AB - Methionine synthase (MS) catalyzes methylation of homocysteine, the last step in
the biosynthesis of methionine, which is essential for the regeneration of
tetrahydrofolate and biosynthesis of S-adenosylmethionine. Here, we report that
MS is localized to the nucleus of Pichia pastoris and Candida albicans but is
cytoplasmic in Saccharomyces cerevisiae The P. pastoris strain carrying a
deletion of the MET6 gene encoding MS (Ppmet6) exhibits methionine as well as
adenine auxotrophy indicating that MS is required for methionine as well as
adenine biosynthesis. Nuclear localization of P. pastoris MS (PpMS) was abrogated
by the deletion of 107 C-terminal amino acids or the R742A mutation. In silico
analysis of the PpMS structure indicated that PpMS may exist in a dimer-like
configuration in which Arg-742 of a monomer forms a salt bridge with Asp-113 of
another monomer. Biochemical studies indicate that R742A as well as D113R
mutations abrogate nuclear localization of PpMS and its ability to reverse
methionine auxotrophy of Ppmet6 Thus, association of two PpMS monomers through
the interaction of Arg-742 and Asp-113 is essential for catalytic activity and
nuclear localization. When PpMS is targeted to the cytoplasm employing a
heterologous nuclear export signal, it is expressed at very low levels and is
unable to reverse methionine and adenine auxotrophy of Ppmet6 Thus, nuclear
localization is essential for the stability and function of MS in P. pastoris. We
conclude that nuclear localization of MS is a unique feature of respiratory
yeasts such as P. pastoris and C. albicans, and it may have novel moonlighting
functions in the nucleus.
PMID- 28701467
TI - The Cross-Species Mycobacterial Growth Inhibition Assay (MGIA) Project, 2010
2014.
AB - The development of a functional biomarker assay in the tuberculosis (TB) field
would be widely recognized as a major advance in efforts to develop and to test
novel TB vaccine candidates efficiently. We present preliminary studies using
mycobacterial growth inhibition assays (MGIAs) to detect Mycobacterium bovis BCG
vaccine responses across species, and we extend this work to determine whether a
standardized MGIA can be applied in characterizing new TB vaccines. The
comparative MGIA studies reviewed here aimed to evaluate robustness,
reproducibility, and ability to reflect in vivo responses. In doing so, they have
laid the foundation for the development of a MGIA that can be standardized and
potentially qualified. A major challenge ahead lies in better understanding the
relationships between in vivo protection, in vitro growth inhibition, and the
immune mechanisms involved. The final outcome would be a MGIA that could be used
with confidence in TB vaccine trials. We summarize data arising from this
project, present a strategy to meet the goals of developing a functional assay
for TB vaccine testing, and describe some of the challenges encountered in
performing and transferring such assays.
PMID- 28701465
TI - The yeast kinesin-5 Cin8 interacts with the microtubule in a noncanonical manner.
AB - Kinesin motors play central roles in establishing and maintaining the mitotic
spindle during cell division. Unlike most other kinesins, Cin8, a kinesin-5 motor
in Saccharomyces cerevisiae, can move bidirectionally along microtubules,
switching directionality according to biochemical conditions, a behavior that
remains largely unexplained. To this end, we used biochemical rate and
equilibrium constant measurements as well as cryo-electron microscopy
methodologies to investigate the microtubule interactions of the Cin8 motor
domain. These experiments unexpectedly revealed that, whereas Cin8 ATPase
kinetics fell within measured ranges for kinesins (especially kinesin-5
proteins), approximately four motors can bind each alphabeta-tubulin dimer within
the microtubule lattice. This result contrasted with those observations on other
known kinesins, which can bind only a single "canonical" site per tubulin dimer.
Competition assays with human kinesin-5 (Eg5) only partially abrogated this
behavior, indicating that Cin8 binds microtubules not only at the canonical site,
but also one or more separate ("noncanonical") sites. Moreover, we found that
deleting the large, class-specific insert in the microtubule-binding loop 8
reverts Cin8 to one motor per alphabeta-tubulin in the microtubule. The novel
microtubule-binding mode of Cin8 identified here provides a potential explanation
for Cin8 clustering along microtubules and potentially may contribute to the
mechanism for direction reversal.
PMID- 28701468
TI - Rubella Surveillance and Diagnostic Testing among a Low-Prevalence Population,
New York City, 2012-2013.
AB - The New York City Department of Health and Mental Hygiene (DOHMH) receives
clinical and laboratory reports for rubella. Because rubella immunoglobulin M
(IgM) assays may produce false-positive results and rubella infections may be
asymptomatic, interpretation of positive IgM results can be challenging. Rubella
reports received by DOHMH in 2012 to 2013 were reviewed. The rubella IgM testing
purpose was determined through case investigation. Results of IgM testing by
indirect enzyme-linked immunosorbent assay (ELISA) and capture enzyme immunoassay
(EIA) were compared to determine positive predictive value (PPV) and specificity.
DOHMH received 199 rubella reports; 2 were true cases. Of all reports, 77.9% were
tested for rubella IgM erroneously, 19.6% were tested for diagnostic purposes,
2.0% had unknown test purpose, and 0.5% were not tested. PPV of indirect ELISA
was 6% overall, 14% for diagnostic tests, and 0% for tests ordered erroneously.
PPV of capture EIA was 29% overall, 50% for diagnostic tests, and 0% for tests
ordered erroneously. Overall, specificity was 52% for indirect ELISA and 85% for
capture EIA. Limiting rubella IgM testing to patients for whom rubella diagnosis
is suspected and using a more specific IgM assay have the potential to reduce
false-positive rubella IgM results.
PMID- 28701469
TI - Long-Term Outcomes and Prognostic Factors of Complications in Takayasu Arteritis:
A Multicenter Study of 318 Patients.
AB - BACKGROUND: Because of the wide variation in the course of Takayasu arteritis
(TA), predicting outcome is challenging. We assess long-term outcome and
prognosis factors for vascular complications in patients with TA. METHODS: A
retrospective multicenter study of characteristics and outcomes of 318 patients
with TA fulfilling American College of Rheumatology and Ishikawa criteria was
analyzed. Factors associated with event-free survival, relapse-free survival, and
incidences of vascular complications were assessed. Risk factors for vascular
complications were identified in a multivariable model. RESULTS: The median age
at TA diagnosis was 36 [25-47] years, and 276 patients (86.8%) were women. After
a median follow-up of 6.1 years, relapses were observed in 43%, vascular
complications in 38%, and death in 5%. Progressive clinical course was observed
in 45%, carotidodynia in 10%, and retinopathy in 4%. The 5- and 10-year event
free survival, relapse-free survival, and complication-free survival were 48.2%
(42.2; 54.9) and 36.4% (30.3; 43.9), 58.6% (52.7; 65.1) and 47.7% (41.2; 55.1),
and 69.9% (64.3; 76.0) and 53.7% (46.8; 61.7), respectively. Progressive disease
course (P=0.018) and carotidynia (P=0.036) were independently associated with
event-free survival. Male sex (P=0.048), elevated C-reactive protein (P=0.013),
and carotidynia (P=0.003) were associated with relapse-free survival. Progressive
disease course (P=0.017), thoracic aorta involvement (P=0.009), and retinopathy
(P=0.002) were associated with complication-free survival. CONCLUSIONS: This
nationwide study shows that 50% of patients with TA will relapse and experience a
vascular complication <=10 years from diagnosis. We identified specific
characteristics that identified those at highest risk for subsequent vascular
complications.
PMID- 28701470
TI - Effect of Ferric Carboxymaltose on Exercise Capacity in Patients With Chronic
Heart Failure and Iron Deficiency.
AB - BACKGROUND: Iron deficiency is common in patients with heart failure (HF) and is
associated with reduced exercise capacity and poor outcomes. Whether correction
of iron deficiency with (intravenous) ferric carboxymaltose (FCM) affects peak
oxygen consumption [peak VO2], an objective measure of exercise intolerance in
HF, has not been examined. METHODS: We studied patients with systolic HF (left
ventricular ejection fraction <=45%) and mild to moderate symptoms despite
optimal HF medication. Patients were randomized 1:1 to treatment with FCM for 24
weeks or standard of care. The primary end point was the change in peak VO2 from
baseline to 24 weeks. Secondary end points included the effect on hematinic and
cardiac biomarkers, quality of life, and safety. For the primary analysis,
patients who died had a value of 0 imputed for 24-week peak VO2. Additional
sensitivity analyses were performed to determine the impact of imputation of
missing peak VO2 data. RESULTS: A total of 172 patients with HF were studied and
received FCM (n=86) or standard of care (control group, n=86). At baseline, the
groups were well matched; mean age was 64 years, 75% were male, mean left
ventricular ejection fraction was 32%, and peak VO2 was 13.5 mL/min/kg. FCM
significantly increased serum ferritin and transferrin saturation. At 24 weeks,
peak VO2 had decreased in the control group (least square means -1.19+/-0.389
mL/min/kg) but was maintained on FCM (-0.16+/-0.387 mL/min/kg; P=0.020 between
groups). In a sensitivity analysis, in which missing data were not imputed, peak
VO2 at 24 weeks decreased by -0.63+/-0.375 mL/min/kg in the control group and by
0.16+/-0.373 mL/min/kg in the FCM group; P=0.23 between groups). Patients' global
assessment and functional class as assessed by the New York Heart Association
improved on FCM versus standard of care. CONCLUSIONS: Treatment with intravenous
FCM in patients with HF and iron deficiency improves iron stores. Although a
favorable effect on peak VO2 was observed on FCM, compared with standard of care
in the primary analysis, this effect was highly sensitive to the imputation
strategy for peak VO2 among patients who died. Whether FCM is associated with an
improved outcome in these high-risk patients needs further study. CLINICAL TRIAL
REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01394562.
PMID- 28701471
TI - Effects of hypoxia and ocean acidification on the upper thermal niche boundaries
of coral reef fishes.
AB - Rising ocean temperatures are predicted to cause a poleward shift in the
distribution of marine fishes occupying the extent of latitudes tolerable within
their thermal range boundaries. A prevailing theory suggests that the upper
thermal limits of fishes are constrained by hypoxia and ocean acidification.
However, some eurythermal fish species do not conform to this theory, and
maintain their upper thermal limits in hypoxia. Here we determine if the same is
true for stenothermal species. In three coral reef fish species we tested the
effect of hypoxia on upper thermal limits, measured as critical thermal maximum
(CTmax). In one of these species we also quantified the effect of hypoxia on
oxygen supply capacity, measured as aerobic scope (AS). In this species we also
tested the effect of elevated CO2 (simulated ocean acidification) on the hypoxia
sensitivity of CTmax We found that CTmax was unaffected by progressive hypoxia
down to approximately 35 mmHg, despite a substantial hypoxia-induced reduction in
AS. Below approximately 35 mmHg, CTmax declined sharply with water oxygen tension
(PwO2). Furthermore, the hypoxia sensitivity of CTmax was unaffected by elevated
CO2 Our findings show that moderate hypoxia and ocean acidification do not
constrain the upper thermal limits of these tropical, stenothermal fishes.
PMID- 28701472
TI - Arterial grafting for coronary revascularisation and the illusive search for
truth.
PMID- 28701473
TI - Zbtb7a induction in alveolar macrophages is implicated in anti-HLA-mediated lung
allograft rejection.
AB - Chronic rejection significantly limits long-term success of solid organ
transplantation. De novo donor-specific antibodies (DSAs) to mismatched donor
human leukocyte antigen after human lung transplantation predispose lung grafts
to chronic rejection. We sought to delineate mediators and mechanisms of DSA
pathogenesis and to define early inflammatory events that trigger chronic
rejection in lung transplant recipients and obliterative airway disease, a
correlate of human chronic rejection, in mouse. Induction of transcription factor
zinc finger and BTB domain containing protein 7a (Zbtb7a) was an early response
critical in the DSA-induced chronic rejection. A cohort of human lung transplant
recipients who developed DSA and chronic rejection demonstrated greater Zbtb7a
expression long before clinical diagnosis of chronic rejection compared to
nonrejecting lung transplant recipients with stable pulmonary function.
Expression of DSA-induced Zbtb7a was restricted to alveolar macrophages (AMs),
and selective disruption of Zbtb7a in AMs resulted in less bronchiolar occlusion,
low immune responses to lung-restricted self-antigens, and high protection from
chronic rejection in mice. Additionally, in an allogeneic cell transfer protocol,
antigen presentation by AMs was Zbtb7a-dependent where AMs deficient in Zbtb7a
failed to induce antibody and T cell responses. Collectively, we demonstrate that
AMs play an essential role in antibody-induced pathogenesis of chronic rejection
by regulating early inflammation and lung-restricted humoral and cellular
autoimmunity.
PMID- 28701474
TI - Detecting human coronary inflammation by imaging perivascular fat.
AB - Early detection of vascular inflammation would allow deployment of targeted
strategies for the prevention or treatment of multiple disease states. Because
vascular inflammation is not detectable with commonly used imaging modalities, we
hypothesized that phenotypic changes in perivascular adipose tissue (PVAT)
induced by vascular inflammation could be quantified using a new computerized
tomography (CT) angiography methodology. We show that inflamed human vessels
release cytokines that prevent lipid accumulation in PVAT-derived preadipocytes
in vitro, ex vivo, and in vivo. We developed a three-dimensional PVAT analysis
method and studied CT images of human adipose tissue explants from 453 patients
undergoing cardiac surgery, relating the ex vivo images with in vivo CT scan
information on the biology of the explants. We developed an imaging metric, the
CT fat attenuation index (FAI), that describes adipocyte lipid content and size.
The FAI has excellent sensitivity and specificity for detecting tissue
inflammation as assessed by tissue uptake of 18F-fluorodeoxyglucose in positron
emission tomography. In a validation cohort of 273 subjects, the FAI gradient
around human coronary arteries identified early subclinical coronary artery
disease in vivo, as well as detected dynamic changes of PVAT in response to
variations of vascular inflammation, and inflamed, vulnerable atherosclerotic
plaques during acute coronary syndromes. Our study revealed that human vessels
exert paracrine effects on the surrounding PVAT, affecting local intracellular
lipid accumulation in preadipocytes, which can be monitored using a CT imaging
approach. This methodology can be implemented in clinical practice to
noninvasively detect plaque instability in the human coronary vasculature.
PMID- 28701475
TI - HIF activation causes synthetic lethality between the VHL tumor suppressor and
the EZH1 histone methyltransferase.
AB - Inactivation of the von Hippel-Lindau tumor suppressor protein (pVHL) is the
signature lesion in the most common form of kidney cancer, clear cell renal cell
carcinoma (ccRCC). pVHL loss causes the transcriptional activation of hypoxia
inducible factor (HIF) target genes, including many genes that encode histone
lysine demethylases. Moreover, chromatin regulators are frequently mutated in
this disease. We found that ccRCC displays increased H3K27 acetylation and a
shift toward mono- or unmethylated H3K27 caused by an HIF-dependent increase in
H3K27 demethylase activity. Using a focused short hairpin RNA library, as well as
CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 (CRISPR
associated protein 9) and a pharmacological inhibitor, we discovered that pVHL
defective ccRCC cells are hyperdependent on the H3K27 methyltransferase EZH1 for
survival. Therefore, targeting EZH1 could be therapeutically useful in ccRCC.
PMID- 28701477
TI - Accelerating the production of insulating brain cells.
AB - A 3D hydrogel enables rapid and scalable production of oligodendrocyte progenitor
cells for transplantation to treat demyelination diseases.
PMID- 28701476
TI - Detection of early pancreatic ductal adenocarcinoma with thrombospondin-2 and
CA19-9 blood markers.
AB - Markers are needed to facilitate early detection of pancreatic ductal
adenocarcinoma (PDAC), which is often diagnosed too late for effective therapy.
Starting with a PDAC cell reprogramming model that recapitulated the progression
of human PDAC, we identified secreted proteins and tested a subset as potential
markers of PDAC. We optimized an enzyme-linked immunosorbent assay (ELISA) using
plasma samples from patients with various stages of PDAC, from individuals with
benign pancreatic disease, and from healthy controls. A phase 1 discovery study
(n = 20), a phase 2a validation study (n = 189), and a second phase 2b validation
study (n = 537) revealed that concentrations of plasma thrombospondin-2 (THBS2)
discriminated among all stages of PDAC consistently. The receiver operating
characteristic (ROC) c-statistic was 0.76 in the phase 1 study, 0.84 in the phase
2a study, and 0.87 in the phase 2b study. The plasma concentration of THBS2 was
able to discriminate resectable stage I cancer as readily as stage III/IV PDAC
tumors. THBS2 plasma concentrations combined with those for CA19-9, a previously
identified PDAC marker, yielded a c-statistic of 0.96 in the phase 2a study and
0.97 in the phase 2b study. THBS2 data improved the ability of CA19-9 to
distinguish PDAC from pancreatitis. With a specificity of 98%, the combination of
THBS2 and CA19-9 yielded a sensitivity of 87% for PDAC in the phase 2b study. A
THBS2 and CA19-9 blood marker panel measured with a conventional ELISA may
improve the detection of patients at high risk for PDAC.
PMID- 28701478
TI - Conjugation does not conquer all in cancer nanotherapy.
AB - Vaccination with potato virus X nanoparticles enhances the efficacy of
traditional doxorubicin anticancer therapy against a mouse melanoma tumor model.
PMID- 28701479
TI - On the origin of relapse in AML.
AB - Preexisting therapy-resistant leukemia stem cell populations underlie the
cellular origin of relapse in acute myeloid leukemia.
PMID- 28701480
TI - Shining new light on migraine.
AB - Migraine-related photophobia is multifaceted and may be mediated by numerous
pathways.
PMID- 28701481
TI - Place and Grid Cells in a Loop: Implications for Memory Function and Spatial
Coding.
AB - Place cells in the hippocampus and grid cells in the medial entorhinal cortex
have different codes for space. However, how one code relates to the other is ill
understood. Based on the anatomy of the entorhinal-hippocampal circuitry, we
constructed a model of place and grid cells organized in a loop to investigate
their mutual influence in the establishment of their codes for space. Using
computer simulations, we first replicated experiments in rats that measured place
and grid cell activity in different environments, and then assessed which
features of the model account for different phenomena observed in
neurophysiological data, such as pattern completion and pattern separation,
global and rate remapping of place cells, and realignment of grid cells. We found
that (1) the interaction between grid and place cells converges quickly; (2) the
spatial code of place cells does not require, but is altered by, grid cell input;
(3) plasticity in sensory inputs to place cells is key for pattern completion but
not pattern separation; (4) grid realignment can be explained in terms of place
cell remapping as opposed to the other way around; (5) the switch between global
and rate remapping is self-organized; and (6) grid cell input to place cells
helps stabilize their code under noisy and/or inconsistent sensory input. We
conclude that the hippocampus-entorhinal circuit uses the mutual interaction of
place and grid cells to encode the surrounding environment and propose a theory
on how such interdependence underlies the formation and use of the cognitive
map.SIGNIFICANCE STATEMENT The mammalian brain implements a positional system
with two key pieces: place and grid cells. To gain insight into the dynamics of
place and grid cell interaction, we built a computational model with the two cell
types organized in a loop. The proposed model accounts for differences in how
place and grid cells represent different environments and provides a new
interpretation in which place and grid cells mutually interact to form a coupled
code for space.
PMID- 28701482
TI - Analysis of RIM Expression and Function at Mouse Photoreceptor Ribbon Synapses.
AB - RAB3A-interacting molecule (RIM) proteins are important regulators of transmitter
release from active zones. At conventional chemical synapses, RIMs contribute
substantially to vesicle priming and docking and their loss reduces the readily
releasable pool of synaptic vesicles by up to 75%. The priming function of RIMs
is mediated via the formation of a tripartite complex with Munc13 and RAB3A,
which brings synaptic vesicles in close proximity to Ca2+ channels and the fusion
site and activates Munc13. We reported previously that, at mouse photoreceptor
ribbon synapses, vesicle priming is Munc13 independent. In this study, we
examined RIM expression, distribution, and function at male and female mouse
photoreceptor ribbon synapses. We provide evidence that RIM1alpha and RIM1beta
are highly likely absent from mouse photoreceptors and that RIM2alpha is the
major large RIM isoform present at photoreceptor ribbon synapses. We show that
mouse photoreceptors predominantly express RIM2 variants that lack the
interaction domain for Munc13. Loss of full-length RIM2alpha in a RIM2alpha
mutant mouse only marginally perturbs photoreceptor synaptic transmission. Our
findings therefore strongly argue for a priming mechanism at the photoreceptor
ribbon synapse that is independent of the formation of a RIM-Munc13-RAB3A complex
and thus provide further evidence for a fundamental difference between
photoreceptor ribbon synapses and conventional chemical synapses in synaptic
vesicle exocytosis.SIGNIFICANCE STATEMENT RAB3A-interacting molecules 1 and 2
(RIM1/2) are essential regulators of exocytosis. At conventional chemical
synapses, their function involves Ca2+ channel clustering and synaptic vesicle
priming and docking through interactions with Munc13 and RAB3A, respectively.
Examining wild-type and RIM2 mutant mice, we show here that the sensory
photoreceptor ribbon synapses most likely lack RIM1 and predominantly express
RIM2 variants that lack the interaction domain for Munc13. Our findings
demonstrate that the photoreceptor-specific RIM variants are not essential for
synaptic vesicle priming at photoreceptor ribbon synapses, which represents a
fundamental difference between photoreceptor ribbon synapses and conventional
chemical synapses with respect to synaptic vesicle priming mechanisms.
PMID- 28701483
TI - The Shigella type III effector IpgD recodes Ca2+ signals during invasion of
epithelial cells.
AB - The role of second messengers in the diversion of cellular processes by pathogens
remains poorly studied despite their importance. Among these, Ca2+ virtually
regulates all known cell processes, including cytoskeletal reorganization,
inflammation, or cell death pathways. Under physiological conditions, cytosolic
Ca2+ increases are transient and oscillatory, defining the so-called Ca2+ code
that links cell responses to specific Ca2+ oscillatory patterns. During cell
invasion, Shigella induces atypical local and global Ca2+ signals. Here, we show
that by hydrolyzing phosphatidylinositol-(4,5)bisphosphate, the Shigella type III
effector IpgD dampens inositol-(1,4,5)trisphosphate (InsP3) levels. By modifying
InsP3 dynamics and diffusion, IpgD favors the elicitation of long-lasting local
Ca2+ signals at Shigella invasion sites and converts Shigella-induced global
oscillatory responses into erratic responses with atypical dynamics and
amplitude. Furthermore, IpgD eventually inhibits InsP3-dependent responses during
prolonged infection kinetics. IpgD thus acts as a pathogen regulator of the Ca2+
code implicated in a versatility of cell functions. Consistent with this
function, IpgD prevents the Ca2+-dependent activation of calpain, thereby
preserving the integrity of cell adhesion structures during the early stages of
infection.
PMID- 28701484
TI - SIRT1 regulates macrophage self-renewal.
AB - Mature differentiated macrophages can self-maintain by local proliferation in
tissues and can be extensively expanded in culture under specific conditions, but
the mechanisms of this phenomenon remain only partially defined. Here, we show
that SIRT1, an evolutionary conserved regulator of life span, positively affects
macrophage self-renewal ability in vitro and in vivo Overexpression of SIRT1
during bone marrow-derived macrophage differentiation increased their
proliferative capacity. Conversely, decrease of SIRT1 expression by shRNA
inactivation, CRISPR/Cas9 mediated deletion and pharmacological inhibition
restricted macrophage self-renewal in culture. Furthermore, pharmacological SIRT1
inhibition in vivo reduced steady state and cytokine-induced proliferation of
alveolar and peritoneal macrophages. Mechanistically, SIRT1 inhibition negatively
regulated G1/S transition, cell cycle progression and a network of self-renewal
genes. This included inhibition of E2F1 and Myc and concomitant activation of
FoxO1, SIRT1 targets mediating cell cycle progression and stress response,
respectively. Our findings indicate that SIRT1 is a key regulator of macrophage
self-renewal that integrates cell cycle and longevity pathways. This suggests
that macrophage self-renewal might be a relevant parameter of ageing.
PMID- 28701486
TI - Long Noncoding RNA and Cancer: A New Paradigm.
AB - In addition to mutations or aberrant expression in the protein-coding genes,
mutations and misregulation of noncoding RNAs, in particular long noncoding RNAs
(lncRNA), appear to play major roles in cancer. Genome-wide association studies
of tumor samples have identified a large number of lncRNAs associated with
various types of cancer. Alterations in lncRNA expression and their mutations
promote tumorigenesis and metastasis. LncRNAs may exhibit tumor-suppressive and
promoting (oncogenic) functions. Because of their genome-wide expression patterns
in a variety of tissues and their tissue-specific expression characteristics,
lncRNAs hold strong promise as novel biomarkers and therapeutic targets for
cancer. In this article, we have reviewed the emerging functions and association
of lncRNAs in different types of cancer and discussed their potential
implications in cancer diagnosis and therapy. Cancer Res; 77(15); 3965-81.
(c)2017 AACR.
PMID- 28701485
TI - GT-rich promoters can drive RNA pol II transcription and deposition of H2A.Z in
African trypanosomes.
AB - Genome-wide transcription studies are revealing an increasing number of
"dispersed promoters" that, unlike "focused promoters", lack well-conserved
sequence motifs and tight regulation. Dispersed promoters are nevertheless marked
by well-defined chromatin structures, suggesting that specific sequence elements
must exist in these unregulated promoters. Here, we have analyzed regions of
transcription initiation in the eukaryotic parasite Trypanosoma brucei, in which
RNA polymerase II transcription initiation occurs over broad regions without
distinct promoter motifs and lacks regulation. Using a combination of site
specific and genome-wide assays, we identified GT-rich promoters that can drive
transcription and promote the targeted deposition of the histone variant H2A.Z in
a genomic context-dependent manner. In addition, upon mapping nucleosome
occupancy at high resolution, we find nucleosome positioning to correlate with
RNA pol II enrichment and gene expression, pointing to a role in RNA maturation.
Nucleosome positioning may thus represent a previously unrecognized layer of gene
regulation in trypanosomes. Our findings show that even highly dispersed,
unregulated promoters contain specific DNA elements that are able to induce
transcription and changes in chromatin structure.
PMID- 28701487
TI - Differential Event Rates and Independent Predictors of Long-Term Major
Cardiovascular Events and Death in 5795 Patients With Unprotected Left Main
Coronary Artery Disease Treated With Stents, Bypass Surgery, or Medication:
Insights From a Large International Multicenter Registry.
AB - BACKGROUND: Identifying predictive factors for major cardiovascular events and
death in patients with unprotected left main coronary artery disease is of great
clinical value for risk stratification and possible guidance for tailored
preventive strategies. METHODS AND RESULTS: The Interventional Research
Incorporation Society-Left MAIN Revascularization registry included 5795 patients
with unprotected left main coronary artery disease (percutaneous coronary
intervention, n=2850; coronary-artery bypass grafting, n=2337; medication alone,
n=608). We analyzed the incidence and independent predictors of major adverse
cardiac and cerebrovascular events (MACCE; a composite of death, MI, stroke, or
repeat revascularization) and all-cause mortality in each treatment stratum.
During follow-up (median, 4.3 years), the rates of MACCE and death were
substantially higher in the medical group than in the percutaneous coronary
intervention and coronary-artery bypass grafting groups (P<0.001). In the
percutaneous coronary intervention group, the 3 strongest predictors for MACCE
were chronic renal failure, old age (>=65 years), and previous heart failure;
those for all-cause mortality were chronic renal failure, old age, and low
ejection fraction. In the coronary-artery bypass grafting group, old age, chronic
renal failure, and low ejection fraction were the 3 strongest predictors of MACCE
and death. In the medication group, old age, low ejection fraction, and diabetes
mellitus were the 3 strongest predictors of MACCE and death. CONCLUSIONS: Among
patients with unprotected left main coronary artery disease, the key clinical
predictors for MACCE and death were generally similar regardless of index
treatment. This study provides effect estimates for clinically relevant
predictors of long-term clinical outcomes in real-world left main coronary artery
patients, providing possible guidance for tailored preventive strategies.
CLINICAL TRIAL REGISTRATION: URL: https://clinicaltrials.gov. Unique identifier:
NCT01341327.
PMID- 28701490
TI - Correction to: Sympathetic Neural and Hemodynamic Responses During Cold Pressor
Test in Elderly Blacks and Whites.
PMID- 28701491
TI - Correction to: Building on a Legacy of Hypertension Research: Charting Our Future
Together.
PMID- 28701488
TI - Comparative Biomechanical Behavior and Healing Profile of a Novel Thinned Wall
Ultrahigh Molecular Weight Amorphous Poly-l-Lactic Acid Sirolimus-Eluting
Bioresorbable Coronary Scaffold.
AB - BACKGROUND: Mechanical strength of bioresorbable scaffolds (BRS) is highly
dependent on strut dimensions and polymer features. To date, the successful
development of thin-walled BRS has been challenging. We compared the
biomechanical behavior and vascular healing profile of a novel thin-walled (115
um) sirolimus-eluting ultrahigh molecular weight amorphous poly-l-lactic acid
based BRS (APTITUDE, Amaranth Medical [AMA]) to Absorb (bioresorbable vascular
scaffold [BVS]) using different experimental models. METHODS AND RESULTS: In
vitro biomechanical testing showed no fractures in the AMA-BRS when overexpanded
1.3 mm above nominal dilatation values (~48%) and lower number of fractures on
accelerated cycle testing over time (at 21 K cycles=20.0 [19.5-20.5] in BVS
versus 4.0 [3.0-4.3] in AMA-BRS). In the healing response study, 35 AMA-BRS and
23 BVS were implanted in 58 coronary arteries of 23 swine and followed-up to 180
days. Scaffold strut healing was evaluated in vivo using weekly optical coherence
tomography analysis. At 14 days, the AMA-BRS demonstrated a higher percentage of
embedded struts (71.0% [47.6, 89.1] compared with BVS 40.3% [20.5, 63.2];
P=0.01). At 21 days, uncovered struts were still present in the BVS group (3.8%
[2.1, 10.2]). Histopathology revealed lower area stenosis (AMA-BRS, 21.0+/-6.1%
versus BVS 31.0+/-4.5%; P=0.002) in the AMA-BRS at 28 days. Neointimal thickness
and inflammatory scores were comparable between both devices at 180 days.
CONCLUSIONS: A new generation thinned wall BRS displayed a more favorable
biomechanical behavior and strut healing profile compared with BVS in normal
porcine coronary arteries. This novel BRS concept has the potential to improve
the clinical outcomes of current generation BRS.
PMID- 28701492
TI - Behavioral-variant frontotemporal dementia: Distinct phenotypes with unique
functional profiles.
AB - OBJECTIVE: To identify distinct behavioral phenotypes of behavioral-variant
frontotemporal dementia (bvFTD) and to elucidate differences in functional,
neuroimaging, and progression to residential care placement. METHODS: Eighty
eight patients with bvFTD were included in a cluster analysis applying levels of
disinhibition and apathy (Cambridge Behavioural Inventory-Revised) to identify
phenotypic subgroups. Between-group (Kruskal-Wallis, Mann-Whitney U) functional
differences (Disability Assessment for Dementia) and time to residential care
placement (survival analyses) were examined. Cortical thickness differences
(whole-brain MRI) were analyzed in patients with bvFTD vs healthy controls (n =
30) and between phenotypic subgroups. RESULTS: Four phenotypic subgroups were
identified: primary severe apathy (n = 26), severe apathy and disinhibition (n =
26), mild apathy and disinhibition (n = 27), and primary severe disinhibition (n
= 9). Patients with severely apathetic phenotypes were more functionally impaired
and had more extensive brain atrophy than those with mild apathy or severe
disinhibition alone. Further imaging analyses indicated that the right middle
temporal region is critical for the development of disinhibition, an association
that remains with disease progression and in the context of severe apathy.
Finally, no difference in time to residential care admission was found between
phenotypes. CONCLUSIONS: This study reveals that different clinical behavioral
phenotypes of bvFTD have differing profiles of functional decline and distinct
patterns of associated cortical changes. These findings emphasize the importance
of apathy in functional impairment, highlight the role of the right temporal
region in disinhibition, and suggest that disability may be a sensitive outcome
measure for treatments targeting reduction of apathy. These phenotypes could also
support understanding of prognosis and clinical management.
PMID- 28701493
TI - The CREST-E study of creatine for Huntington disease: A randomized controlled
trial.
AB - OBJECTIVE: To investigate whether creatine administration could slow progressive
functional decline in adults with early symptoms of Huntington disease. METHODS:
We conducted a multicenter, randomized, double-blind, placebo-controlled study of
up to 40 g daily of creatine monohydrate in participants with stage I and II HD
treated for up to 48 months. The primary outcome measure was the rate of change
in total functional capacity (TFC) between baseline and end of follow-up.
Secondary outcome measures included changes in additional clinical scores,
tolerability, and quality of life. Safety was assessed by adverse events and
laboratory studies. RESULTS: At 46 sites in North America, Australia, and New
Zealand, 553 participants were randomized to creatine (275) or placebo (278). The
trial was designed to enroll 650 patients, but was halted for futility after the
first interim analysis. The estimated rates of decline in the primary outcome
measure (TFC) were 0.82 points per year for participants on creatine, 0.70 points
per year for participants on placebo, favoring placebo (nominal 95% confidence
limits -0.11 to 0.35). Adverse events, mainly gastrointestinal, were
significantly more common in participants on creatine. Serious adverse events,
including deaths, were more frequent in the placebo group. Subgroup analysis
suggested that men and women may respond differently to creatine treatment.
CONCLUSIONS: Our data do not support the use of creatine treatment for delaying
functional decline in early manifest HD. CLINICALTRIALSGOV IDENTIFIER:
NCT00712426. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence
that for patients with early symptomatic HD, creatine monohydrate is not
beneficial for slowing functional decline.
PMID- 28701494
TI - Loss of phosphodiesterase 4 in Parkinson disease: Relevance to cognitive
deficits.
AB - OBJECTIVE: To assess in vivo the expression of phosphodiesterase 4 (PDE4) and its
relevance to cognitive symptoms in patients with Parkinson disease (PD) using
[11C]rolipram PET. METHODS: We studied 12 levodopa-treated patients with PD with
no concurrent diagnosis of mild cognitive impairment or dementia. Their data were
compared with those from 12 healthy controls. All participants underwent
neuropsychiatric and cognitive assessment using the Cambridge Neuropsychological
Test Automated Battery. Parametric images of [11C]rolipram volume of distribution
(VT) values were determined with the Logan plot. RESULTS: Patients with PD
performed worse than healthy controls in cognitive examinations assessing
psychomotor speed, episodic memory, and spatial working memory and executive
function. Patients with PD showed reductions in [11C]rolipram VT compared to
healthy controls, in the caudate (28%), thalamus (23%), hypothalamus (32%), and
cortex (16%). Within thalamic subregions, [11C]rolipram VT values in patients
with PD were decreased by 12%-32%, with most marked decreases observed in
prefrontal and temporal thalamic nuclei, whereas motor nuclei were less affected.
Within the cortex, [11C]rolipram VT values in patients with PD were decreased by
11%-20%, with most marked decreases observed in posterior dorsolateral frontal
cortex, medial frontal cortex, and supplementary motor area, whereas
orbitofrontal cortex was less affected. Worse performance in spatial working
memory correlated with lower [11C]rolipram VT values in posterior dorsolateral
frontal cortex, medial frontal cortex, supplementary motor area, precentral
gyrus, caudate, and prefrontal thalamic nuclei. CONCLUSIONS: Our findings
demonstrate loss of PDE4 expression in the striato-thalamo-cortical circuit,
which is associated with deficits of spatial working memory in patients with PD.
PMID- 28701495
TI - Neurodegenerative and psychiatric diseases among families with amyotrophic
lateral sclerosis.
AB - OBJECTIVE: To estimate risks of neurodegenerative and psychiatric diseases among
patients with amyotrophic lateral sclerosis (ALS) and their families. METHODS: We
conducted a register-based nested case-control study during 1990-2013 in Sweden
to assess whether patients with ALS had higher risks of other neurodegenerative
and psychiatric diseases before diagnosis. We included 3,648 patients with ALS
and 36,480 age-, sex-, and county of birth-matched population controls. We
further conducted a follow-up study of the cases and controls to assess the risks
of other neurodegenerative and psychiatric diseases after ALS diagnosis. To
assess the potential contribution of familial factors, we conducted similar
studies for the relatives of patients with ALS and their controls. RESULTS:
Individuals with previous neurodegenerative or psychiatric diseases had a 49%
increased risk of ALS (odds ratio 1.49, 95% confidence interval 1.35-1.66)
compared to individuals without these diseases. After diagnosis, patients with
ALS had increased risks of other neurodegenerative or psychiatric diseases
(hazard ratio 2.90, 95% confidence interval 2.46-3.43) compared to individuals
without ALS. The strongest associations were noted for frontotemporal dementia,
Parkinson disease, other dementia, Alzheimer disease, neurotic disorders,
depression, stress-related disorders, and drug abuse/dependence. First-degree
relatives of patients with ALS had higher risk of neurodegenerative diseases,
whereas only children of patients with ALS had higher risk of psychiatric
disorders, compared to relatives of the controls. CONCLUSIONS: Familial
aggregation of ALS and other neurodegenerative diseases implies a shared
etiopathogenesis among all neurodegenerative diseases. The increased risk of
psychiatric disorders among patients with ALS and their children might be
attributable to nonmotor symptoms of ALS and severe stress response toward the
diagnosis.
PMID- 28701496
TI - The spectrum of mild traumatic brain injury: A review.
AB - OBJECTIVE: This review provides an in-depth overview of diagnostic schema and
risk factors influencing recovery during the acute, subacute (operationally
defined as up to 3 months postinjury), and chronic injury phases across the full
spectrum of individuals (e.g., athletes to neurosurgery patients) with mild
traumatic brain injury (mTBI). Particular emphasis is placed on the complex
differential diagnoses for patients with prolonged postconcussive symptoms.
METHODS: Select literature review and synthesis. RESULTS: In spite of an increase
in public awareness surrounding the acute and potential long-term effects of
mTBI, the medical field remains fragmented both in terms of the diagnostic
(different criteria proffered by multiple medical organizations) and prognostic
factors that influence patient care. CONCLUSIONS: Given the lack of objective
biomarkers and the spectrum of different disorders that likely encompass mTBI,
clinicians are encouraged to adopt a probabilistic, rather than definitive,
diagnostic and prognostic framework. The relevance of accurately diagnosing and
managing the different manifestations of mTBI becomes clear when one considers
the overall incidence of the disorder (42 million people each year worldwide),
and the different treatment implications for patients with a true
neurodegenerative disorder (e.g., chronic traumatic encephalopathy; rare) vs
potentially treatable conditions (e.g., depression or posttraumatic headache;
frequent).
PMID- 28701497
TI - Teaching neurology to medical students with a simplified version of team-based
learning.
AB - OBJECTIVE: To compare the effect of a simplified version of team-based learning
(sTBL), an active learning/small group instructional strategy, with that of the
traditionally used small group interactive seminars on the acquisition of
knowledge and clinical reasoning (CR) skills. METHODS: Third- and fourth-year
medical students (n = 122) were randomly distributed into 2 groups. A crossover
design was used in which 2 neurologic topics were taught by sTBL and 2 by small
group interactive seminars. Knowledge was assessed with a multiple-choice
question examination (MCQE), CR skills with a key feature problem examination
(KFPE). Questionnaires were used for further methodologic evaluation. RESULTS: No
group differences were found in the MCQE results. sTBL instruction of the topic
"acute altered mental status" was associated with a significantly better student
performance in the KFPE (p = 0.008), with no differences in the other 3 topics
covered. Although both teaching methods were highly rated by the students, a
clear majority voted for sTBL as their preferred future teaching method.
CONCLUSIONS: sTBL served as an equivalent alternative to small group interactive
seminars for imparting knowledge and teaching CR skills, and was particularly
advantageous for teaching CR in the setting of a complex neurologic topic.
Furthermore, students reported a strong preference for the sTBL approach, making
it a promising tool for effectively teaching neurology.
PMID- 28701498
TI - Phosphodiesterase 4: Rethinking cognition in Parkinson disease.
PMID- 28701499
TI - Breastfeeding, ovulatory years, and risk of multiple sclerosis.
AB - OBJECTIVE: To determine whether women who breastfeed their infants longer or have
fewer ovulatory years are at lower risk of developing multiple sclerosis (MS).
METHODS: We recruited women with newly diagnosed MS or its precursor, clinically
isolated syndrome (CIS) (n = 397), and matched controls (n = 433) into the MS
Sunshine Study from the membership of Kaiser Permanente Southern California. A
structured in-person questionnaire was administered to collect the behavioral
(pregnancies, breastfeeding, hormonal contraceptive use) and biological (age at
menarche and menopause, amenorrhea) factors to make up ovulatory years. RESULTS:
Among women who had live births, a cumulative duration of breastfeeding for >=15
months was associated with a reduced risk of MS/CIS (adjusted odds ratio [OR]
0.47, 95% confidence interval [CI] 0.28-0.77; p = 0.003 compared to 0-4 months of
breastfeeding). Being >=15 years of age at menarche was also associated with a
lower risk of MS/CIS (adjusted OR 0.56, 95% CI 0.33-0.96; p = 0.035). Total
ovulatory years and the remaining factors that determine it, including gravidity,
parity, episodes of amenorrhea, and hormonal contraceptive use, as well as age at
first birth, showed no significant association with the risk of MS/CIS.
CONCLUSIONS: Mothers who breastfeed longer may be at lower subsequent risk of
developing multiple sclerosis. This is consistent with the other known maternal
health benefits of breastfeeding and with our previous observation that women
with MS who breastfeed exclusively are at lower risk of postpartum relapses.
PMID- 28701500
TI - Assessing structure and function of myelin in cervical spondylotic myelopathy:
Evidence of demyelination.
AB - PURPOSE: To assess the extent of demyelination in cervical spondylotic myelopathy
(CSM) using myelin water imaging (MWI) and electrophysiologic techniques.
METHODS: Somatosensory evoked potentials (SSEPs) and MWI were acquired in 14
patients with CSM and 18 age-matched healthy controls. MWI was performed on a
3.0T whole body magnetic resonance scanner. Myelin water fraction (MWF) was
extracted for the dorsal columns and whole cord. SSEPs and MWF were also compared
with conventional MRI outcomes, including T2 signal intensity, compression ratio,
maximum spinal cord compression (MSCC), and maximum canal compromise (MCC).
RESULTS: Group analysis showed marked differences in T2 signal intensity,
compression ratio, MSCC, and MCC between healthy controls and patients with CSM.
There were no group differences in MWF and SSEP latencies. However, patients with
CSM with pathologic SSEPs exhibited reduction in MWF (p < 0.05). MWF was also
correlated with SSEP latencies. CONCLUSION: Our findings provide evidence of
decreased myelin content in the spinal cord associated with impaired spinal cord
conduction in patients with CSM. While conventional MRI are of great value to
define the extent of cord compression, they show a limited correlation with
functional deficits (i.e., delayed SSEPs). MWI provides independent and
complementary readouts to spinal cord compression, with a high specificity to
detect impaired conduction.
PMID- 28701501
TI - Blood pressure reduction and noncontrast CT markers of intracerebral hemorrhage
expansion.
AB - OBJECTIVE: To validate various noncontrast CT (NCCT) predictors of hematoma
expansion in a large international cohort of ICH patients and investigate whether
intensive blood pressure (BP) treatment reduces ICH growth and improves outcome
in patients with these markers. METHODS: We analyzed patients enrolled in the
Antihypertensive Treatment of Acute Cerebral Hemorrhage II (ATACH-II) randomized
controlled trial. Participants were assigned to intensive (systolic BP <140 mm
Hg) vs standard (systolic BP <180 mm Hg) treatment within 4.5 hours from onset.
The following NCCT markers were identified: intrahematoma hypodensities, black
hole sign, swirl sign, blend sign, heterogeneous hematoma density, and irregular
shape. ICH expansion was defined as hematoma growth >33% and unfavorable outcome
was defined as modified Rankin Scale score >3 at 90 days. Logistic regression was
used to identify predictors of ICH expansion and explore the association between
NCCT signs and clinical benefit from intensive BP treatment. RESULTS: A total of
989 patients were included (mean age 62 years, 61.9% male), of whom 186/869
experienced hematoma expansion (21.4%) and 361/952 (37.9%) had unfavorable
outcome. NCCT markers independently predicted ICH expansion (all p < 0.01) with
overall accuracy ranging from 61% to 78% and good interrater reliability (k > 0.6
for all markers). There was no evidence of an interaction between NCCT markers
and benefit from intensive BP reduction (all p for interaction >0.10).
CONCLUSIONS: NCCT signs reliably identify ICH patients at high risk of hematoma
growth. However, we found no evidence that patients with these markers
specifically benefit from intensive BP reduction. CLINICALTRIALSGOV IDENTIFIER:
NCT01176565.
PMID- 28701502
TI - Wrist sensor reveals sympathetic hyperactivity and hypoventilation before
probable SUDEP.
PMID- 28701504
TI - Degradation and erosion mechanisms of bioresorbable porous acellular vascular
grafts: an in vitro investigation.
AB - A fundamental mechanism of in situ tissue regeneration from biodegradable
synthetic acellular vascular grafts is the effective interplay between graft
degradation, erosion and the production of extracellular matrix. In order to
understand this crucial process of graft erosion and degradation, we conducted an
in vitro investigation of grafts (n = 4 at days 1, 4, 7, 10 each) exposed to
enzymatic degradation. Herein, we provide constitutive relationships for mass
loss and mechanical properties based on much-needed experimental data.
Furthermore, we formulate a mathematical model to provide a physics-based
framework for understanding graft erosion. A novel finding is that despite their
porous nature, grafts lost mass exponentially via surface erosion demonstrating a
20% reduction in outer diameter and no significant change in apparent density. A
diffusion based, concentration gradient-driven mechanistic model of mass loss
through surface erosion was introduced which can be extended to an in vivo
setting through the use of two degradation parameters. Furthermore, notably,
mechanical properties of degrading grafts did not scale with mass loss. Thus, we
introduced a damage function scaling a neo-Hookean model to describe mechanical
properties of the degrading graft; a refinement to existing mass-dependent growth
and remodelling (G&R) models. This framework can be used to improve accuracy of
well-established G&R theories in biomechanics; tools that predict evolving
structure-function relationships of neotissues and guide graft design.
PMID- 28701503
TI - Taking chances and making mistakes: non-genetic phenotypic heterogeneity and its
consequences for surviving in dynamic environments.
AB - Natural selection has shaped the strategies for survival and growth of
microorganisms. The success of microorganisms depends not only on slow
evolutionary tuning but also on the ability to adapt to unpredictable changes in
their environment. In principle, adaptive strategies range from purely
deterministic mechanisms to those that exploit the randomness intrinsic to many
cellular and molecular processes. Depending on the environment and selective
pressures, particular strategies can lie somewhere along this continuum. In
recent years, non-genetic cell-to-cell differences have received a lot of
attention, not least because of their potential impact on the ability of
microbial populations to survive in dynamic environments. Using several examples,
we describe the origins of spontaneous and induced mechanisms of phenotypic
adaptation. We identify some of the commonalities of these examples and consider
the potential role of chance and constraints in microbial phenotypic adaptation.
PMID- 28701505
TI - Remotely sensed wind speed predicts soaring behaviour in a wide-ranging pelagic
seabird.
AB - Global wind patterns affect flight strategies in many birds, including pelagic
seabirds, many of which use wind-powered soaring to reduce energy costs during at
sea foraging trips and migration. Such long-distance movement patterns are
underpinned by local interactions between wind conditions and flight behaviour,
but these fine-scale relationships are far less well understood. Here we show
that remotely sensed ocean wind speed and direction are highly significant
predictors of soaring behaviour in a migratory pelagic seabird, the Manx
shearwater (Puffinus puffinus). We used high-frequency GPS tracking data (10 Hz)
and statistical behaviour state classification to identify two energetic modes in
at-sea flight, corresponding to flap-like and soar-like flight. We show that
soaring is significantly more likely to occur in tailwinds and crosswinds above a
wind speed threshold of around 8 m s-1, suggesting that these conditions enable
birds to reduce metabolic costs by preferentially soaring over flapping. Our
results suggest a behavioural mechanism by which wind conditions may shape
foraging and migration ecology in pelagic seabirds, and thus indicate that shifts
in wind patterns driven by climate change could impact this and other species.
They also emphasize the emerging potential of high-frequency GPS biologgers to
provide detailed quantitative insights into fine-scale flight behaviour in free
living animals.
PMID- 28701506
TI - Modelling the host-pathogen interactions of macrophages and Candida albicans
using Game Theory and dynamic optimization.
AB - The release of fungal cells following macrophage phagocytosis, called non-lytic
expulsion, is reported for several fungal pathogens. On one hand, non-lytic
expulsion may benefit the fungus in escaping the microbicidal environment of the
phagosome. On the other hand, the macrophage could profit in terms of avoiding
its own lysis and being able to undergo proliferation. To analyse the causes of
non-lytic expulsion and the relevance of macrophage proliferation in the
macrophage-Candida albicans interaction, we employ Evolutionary Game Theory and
dynamic optimization in a sequential manner. We establish a game-theoretical
model describing the different strategies of the two players after phagocytosis.
Depending on the parameter values, we find four different Nash equilibria and
determine the influence of the systems state of the host upon the game. As our
Nash equilibria are a direct consequence of the model parameterization, we can
depict several biological scenarios. A parameter region, where the host response
is robust against the fungal infection, is determined. We further apply dynamic
optimization to analyse whether macrophage mitosis is relevant in the host
pathogen interaction of macrophages and C. albicans For this, we study the
population dynamics of the macrophage-C. albicans interactions and the
corresponding optimal controls for the macrophages, indicating the best
macrophage strategy of switching from proliferation to attacking fungal cells.
PMID- 28701507
TI - The Innate Cytokines IL-25, IL-33, and TSLP Cooperate in the Induction of Type 2
Innate Lymphoid Cell Expansion and Mucous Metaplasia in Rhinovirus-Infected
Immature Mice.
AB - Early-life respiratory viral infection is a risk factor for asthma development.
Rhinovirus (RV) infection of 6-d-old mice, but not mature mice, causes mucous
metaplasia and airway hyperresponsiveness that are associated with the expansion
of lung type 2 innate lymphoid cells (ILC2s) and are dependent on IL-13 and the
innate cytokine IL-25. However, contributions of the other innate cytokines, IL
33 and thymic stromal lymphopoietin (TSLP), to the observed asthma-like phenotype
have not been examined. We reasoned that IL-33 and TSLP expression are also
induced by RV infection in immature mice and are required for maximum ILC2
expansion and mucous metaplasia. We inoculated 6-d-old BALB/c (wild-type) and
TSLP receptor-knockout mice with sham HeLa cell lysate or RV. Selected mice were
treated with neutralizing Abs to IL-33 or recombinant IL-33, IL-25, or TSLP.
ILC2s were isolated from RV-infected immature mice and treated with innate
cytokines ex vivo. RV infection of 6-d-old mice increased IL-33 and TSLP protein
abundance. TSLP expression was localized to the airway epithelium, whereas IL-33
was expressed in epithelial and subepithelial cells. RV-induced mucous
metaplasia, ILC2 expansion, airway hyperresponsiveness, and epithelial cell IL-25
expression were attenuated by anti-IL-33 treatment and in TSLP receptor-knockout
mice. Administration of intranasal IL-33 and TSLP was sufficient for mucous
metaplasia. Finally, TSLP was required for maximal ILC2 gene expression in
response to IL-25 and IL-33. The generation of mucous metaplasia in immature RV
infected mice involves a complex interplay among the innate cytokines IL-25, IL
33, and TSLP.
PMID- 28701508
TI - Prdm1 Regulates Thymic Epithelial Function To Prevent Autoimmunity.
AB - Autoimmunity is largely prevented by medullary thymic epithelial cells (TECs)
through their expression and presentation of tissue-specific Ags to developing
thymocytes, resulting in deletion of self-reactive T cells and supporting
regulatory T cell development. The transcription factor Prdm1 has been implicated
in autoimmune diseases in humans through genome-wide association studies and in
mice using cell type-specific deletion of Prdm1 in T and dendritic cells. In this
article, we demonstrate that Prdm1 functions in TECs to prevent autoimmunity in
mice. Prdm1 is expressed by a subset of mouse TECs, and conditional deletion of
Prdm1 in either Keratin 14- or Foxn1-expressing cells in mice resulted in
multisymptom autoimmune pathology. Notably, the development of Foxp3+ regulatory
T cells occurs normally in the absence of Blimp1. Importantly, nude mice
developed anti-nuclear Abs when transplanted with Prdm1 null TECs, but not wild
type TECs, indicating that Prdm1 functions in TECs to regulate autoantibody
production. We show that Prdm1 acts independently of Aire, a crucial
transcription factor implicated in medullary TEC function. Collectively, our data
highlight a previously unrecognized role for Prdm1 in regulating thymic
epithelial function.
PMID- 28701509
TI - Dendritic Cell-Derived IL-32alpha: A Novel Inhibitory Cytokine of NK Cell
Function.
AB - Cytokines produced by dendritic cells (DCs) can largely determine the direction
of immunity. Transcriptional analysis revealed that besides IL-15, IL-32 was the
only other cytokine expressed by human Langerhans cells. IL-32 is a human
cytokine that exists in four main isoforms. Currently, little is known about the
regulation and function of the various IL-32 isoforms. In this study, we found
that IL-15 is a potent inducer of IL-32alpha in DCs. Because IL-15 promotes NK
cell activation, we investigated the interplay between IL-32 and IL-15 and their
role in NK cell activity. We show that IL-32alpha acts on NK cells to inhibit IL
15-mediated STAT5 phosphorylation and to suppress their IL-15-induced effector
molecule expression and cytolytic capacity. IL-32alpha also acted on DCs by
downregulating IL-15-induced IL-18 production, an important cytokine in NK cell
activity. Blocking IL-32alpha during DC:NK cell coculture enhanced NK cell
effector molecule expression as well as their cytolytic capacity. Taken together,
our findings suggest a feedback inhibition of IL-15-mediated NK cell activity by
IL-32alpha.
PMID- 28701510
TI - Immunomodulatory Molecule IRAK-M Balances Macrophage Polarization and Determines
Macrophage Responses during Renal Fibrosis.
AB - Activation of various innate immune receptors results in IL-1 receptor-associated
kinase (IRAK)-1/IRAK-4-mediated signaling and secretion of proinflammatory
cytokines such as IL-12, IL-6, or TNF-alpha, all of which are implicated in
tissue injury and elevated during tissue remodeling processes. IRAK-M, also known
as IRAK-3, is an inhibitor of proinflammatory cytokine and chemokine expression
in intrarenal macrophages. Innate immune activation contributes to both acute
kidney injury and tissue remodeling that is associated with chronic kidney
disease (CKD). Our study assessed the contribution of macrophages in CKD and the
role of IRAK-M in modulating disease progression. To evaluate the effect of IRAK
M in chronic renal injury in vivo, a mouse model of unilateral ureteral
obstruction (UUO) was employed. The expression of IRAK-M increased within 2 d
after UUO in obstructed compared with unobstructed kidneys. Mice deficient in
IRAK-M were protected from fibrosis and displayed a diminished number of
alternatively activated macrophages. Compared to wild-type mice, IRAK-M-deficient
mice showed reduced tubular injury, leukocyte infiltration, and inflammation
following renal injury as determined by light microscopy, immunohistochemistry,
and intrarenal mRNA expression of proinflammatory and profibrotic mediators.
Taken together, these results strongly support a role for IRAK-M in renal injury
and identify IRAK-M as a possible modulator in driving an alternatively activated
profibrotic macrophage phenotype in UUO-induced CKD.
PMID- 28701511
TI - N-Arachidonoyl Dopamine Modulates Acute Systemic Inflammation via
Nonhematopoietic TRPV1.
AB - N-Arachidonoyl dopamine (NADA) is an endogenous lipid that potently activates the
transient receptor potential vanilloid 1 (TRPV1), which mediates pain and
thermosensation. NADA is also an agonist of cannabinoid receptors 1 and 2. We
have reported that NADA reduces the activation of cultured human endothelial
cells by LPS and TNF-alpha. Thus far, in vivo studies using NADA have focused on
its neurologic and behavioral roles. In this article, we show that NADA potently
decreases in vivo systemic inflammatory responses and levels of the coagulation
intermediary plasminogen activator inhibitor 1 in three mouse models of
inflammation: LPS, bacterial lipopeptide, and polymicrobial intra-abdominal
sepsis. We also found that the administration of NADA increases survival in
endotoxemic mice. Additionally, NADA reduces blood levels of the neuropeptide
calcitonin gene-related peptide but increases the neuropeptide substance P in LPS
treated mice. We demonstrate that the anti-inflammatory effects of NADA are
mediated by TRPV1 expressed by nonhematopoietic cells and provide data suggesting
that neuronal TRPV1 may mediate NADA's anti-inflammatory effects. These results
indicate that NADA has novel TRPV1-dependent anti-inflammatory properties and
suggest that the endovanilloid system might be targeted therapeutically in acute
inflammation.
PMID- 28701512
TI - Imatinib and Nilotinib Off-Target Effects on Human NK Cells, Monocytes, and M2
Macrophages.
AB - Tyrosine kinase inhibitors (TKIs) are used in the clinical management of
hematological neoplasms. Moreover, in solid tumors such as stage 4 neuroblastomas
(NB), imatinib showed benefits that might depend on both on-target and
immunological off-target effects. We investigated the effects of imatinib and
nilotinib on human NK cells, monocytes, and macrophages. High numbers of
monocytes died upon exposure to TKI concentrations similar to those achieved in
patients. Conversely, NK cells were highly resistant to the TKI cytotoxic effect,
were properly activated by immunostimulatory cytokines, and degranulated in the
presence of NB cells. In NB, neither drug reduced the expression of ligands for
activating NK receptors or upregulated that of HLA class I, B7-H3, PD-L1, and PD
L2, molecules that might limit NK cell function. Interestingly, TKIs modulated
the chemokine receptor repertoire of immune cells. Acting at the transcriptional
level, they increased the surface expression of CXCR4, an effect observed also in
NK cells and monocytes of patients receiving imatinib for chronic myeloid
leukemia. Moreover, TKIs reduced the expression of CXCR3 (in NK cells) and CCR1
(in monocytes). Monocytes also decreased the expression of M-CSFR, and low
numbers of cells underwent differentiation toward macrophages. M0 and M2
macrophages were highly resistant to TKIs and maintained their phenotypic and
functional characteristics. Importantly, also in the presence of TKIs, the M2
immunosuppressive polarization was reverted by TLR engagement, and M1-oriented
macrophages fully activated autologous NK cells. Our results contribute to better
interpreting the off-target efficacy of TKIs in tumors and to envisaging
strategies aimed at facilitating antitumor immune responses.
PMID- 28701513
TI - The prion protein regulates glutamate-mediated Ca2+ entry and mitochondrial Ca2+
accumulation in neurons.
AB - The cellular prion protein (PrPC) whose conformational misfolding leads to the
production of deadly prions, has a still-unclarified cellular function despite
decades of intensive research. Following our recent finding that PrPC limits Ca2+
entry via store-operated Ca2+ channels in neurons, we investigated whether the
protein could also control the activity of ionotropic glutamate receptors
(iGluRs). To this end, we compared local Ca2+ movements in primary cerebellar
granule neurons and cortical neurons transduced with genetically encoded Ca2+
probes and expressing, or not expressing, PrPC Our investigation demonstrated
that PrPC downregulates Ca2+ entry through each specific agonist-stimulated iGluR
and after stimulation by glutamate. We found that, although PrP-knockout (KO)
mitochondria were displaced from the plasma membrane, glutamate addition resulted
in a higher mitochondrial Ca2+ uptake in PrP-KO neurons than in their PrPC
expressing counterpart. This was because the increased Ca2+ entry through iGluRs
in PrP-KO neurons led to a parallel increase in Ca2+-induced Ca2+ release via
ryanodine receptor channels. These data thus suggest that PrPC takes part in the
cell apparatus controlling Ca2+ homeostasis, and that PrPC is involved in
protecting neurons from toxic Ca2+ overloads.
PMID- 28701514
TI - Talin - the master of integrin adhesions.
AB - Talin has emerged as the key cytoplasmic protein that mediates integrin adhesion
to the extracellular matrix. In this Review, we draw on experiments performed in
mammalian cells in culture and Drosophila to present evidence that talin is the
most important component of integrin adhesion complexes. We describe how the
properties of this adaptor protein enable it to orchestrate integrin adhesions.
Talin forms the core of integrin adhesion complexes by linking integrins directly
to actin, increasing the affinity of integrin for ligands (integrin activation)
and recruiting numerous proteins. It regulates the strength of integrin adhesion,
senses matrix rigidity, increases focal adhesion size in response to force and
serves as a platform for the building of the adhesion structure. Finally, the
mechano-sensitive structure of talin provides a paradigm for how proteins
transduce mechanical signals to chemical signals.
PMID- 28701516
TI - Blocking TGF-beta and beta-Catenin Epithelial Crosstalk Exacerbates CKD.
AB - The TGF-beta and Wnt/beta-catenin pathways have important roles in modulating
CKD, but how these growth factors affect the epithelial response to CKD is not
well studied. TGF-beta has strong profibrotic effects, but this pleiotropic
factor has many different cellular effects depending on the target cell type. To
investigate how TGF-beta signaling in the proximal tubule, a key target and
mediator of CKD, alters the response to CKD, we injured mice lacking the TGF-beta
type 2 receptor specifically in this epithelial segment. Compared with littermate
controls, mice lacking the proximal tubular TGF-beta receptor had significantly
increased tubular injury and tubulointerstitial fibrosis in two different models
of CKD. RNA sequencing indicated that deleting the TGF-beta receptor in proximal
tubule cells modulated many growth factor pathways, but Wnt/beta-catenin
signaling was the pathway most affected. We validated that deleting the proximal
tubular TGF-beta receptor impaired beta-catenin activity in vitro and in vivo
Genetically restoring beta-catenin activity in proximal tubules lacking the TGF
beta receptor dramatically improved the tubular response to CKD in mice. Deleting
the TGF-beta receptor alters many growth factors, and therefore, this ameliorated
response may be a direct effect of beta-catenin activity or an indirect effect of
beta-catenin interacting with other growth factors. In conclusion, blocking TGF
beta and beta-catenin crosstalk in proximal tubules exacerbates tubular injury in
two models of CKD.
PMID- 28701517
TI - Mesangial Cell Mammalian Target of Rapamycin Complex 1 Activation Results in
Mesangial Expansion.
AB - Human glomerular diseases can be caused by several different diseases, many of
which include mesangial expansion and/or proliferation followed by
glomerulosclerosis. However, molecular mechanisms underlying the pathologic
mesangial changes remain poorly understood. Here, we investigated the role of the
mammalian target of rapamycin complex 1 (mTORC1)-S6 kinase pathway in mesangial
expansion and/or proliferation by ablating an upstream negative regulator,
tuberous sclerosis complex 1 (TSC1), using tamoxifen-induced Foxd1-Cre mice
[Foxd1ER(+) TSC1 mice]. Foxd1ER(+) TSC1 mice showed mesangial expansion with
increased production of collagen IV, collagen I, and alpha-smooth muscle actin in
glomeruli, but did not exhibit significant mesangial proliferation or
albuminuria. Furthermore, rapamycin treatment of Foxd1ER(+) TSC1 mice suppressed
mesangial expansion. Among biopsy specimens from patients with glomerular
diseases, analysis of phosphorylated ribosomal protein S6 revealed mesangial cell
mTORC1 activation in IgA nephropathy and in lupus mesangial proliferative
nephritis but not in the early phase of diabetic nephropathy. In summary,
mesangial cell mTORC1 activation can cause mesangial expansion and has clinical
relevance for human glomerular diseases. This report also confirms that the
tamoxifen-induced mesangium-specific Cre-loxP system is useful for studies
designed to clarify the role of the mesangium in glomerular diseases in adults.
PMID- 28701518
TI - Effect of Cytochrome P450 Metabolites of Arachidonic Acid in Nephrology.
AB - Thirty-five years ago, a third pathway for the metabolism of arachidonic acid by
cytochrome P450 enzymes emerged. Subsequent work revealed that 20
hydroxyeicosatetraenoic and epoxyeicosatrienoic acids formed by these pathways
have essential roles in the regulation of renal tubular and vascular function.
Sequence variants in the genes that produce 20-hydroxyeicosatetraenoic acid are
associated with hypertension in humans, whereas the evidence supporting a role
for variants in the genes that alter levels of epoxyeicosatrienoic acids is less
convincing. Studies in animal models suggest that changes in the production of
cytochrome P450 eicosanoids alter BP. However, the mechanisms involved remain
controversial, especially for 20-hydroxyeicosatetraenoic acid, which has both
vasoconstrictive and natriuretic actions. Epoxyeicosatrienoic acids are
vasodilators with anti-inflammatory properties that oppose the development of
hypertension and CKD; 20-hydroxyeicosatetraenoic acid levels are elevated after
renal ischemia and may protect against injury. Levels of this eicosanoid are also
elevated in polycystic kidney disease and may contribute to cyst formation. Our
review summarizes the emerging evidence that cytochrome P450 eicosanoids have a
role in the pathogenesis of hypertension, polycystic kidney disease, AKI, and
CKD.
PMID- 28701519
TI - Nineteen complex-related factor Prp45 is required for the early stages of
cotranscriptional spliceosome assembly.
AB - Splicing in S. cerevisiae has been shown to proceed cotranscriptionally, but the
nature of the coupling remains a subject of debate. Here, we examine the effect
of nineteen complex-related splicing factor Prp45 (a homolog of SNW1/SKIP) on
cotranscriptional splicing. RNA-sequencing and RT-qPCR showed elevated pre-mRNA
levels but only limited reduction of spliced mRNAs in cells expressing C
terminally truncated Prp45, Prp45(1-169). Assays with a series of reporters
containing the AMA1 intron with regulatable splicing confirmed decreased splicing
efficiency and showed the leakage of unspliced RNAs in prp45(1-169) cells. We
also measured pre-mRNA accumulation of the meiotic MER2 gene, which depends on
the expression of Mer1 factor for splicing. prp45(1-169) cells accumulated
approximately threefold higher levels of MER2 pre-mRNA than WT cells only when
splicing was induced. To monitor cotranscriptional splicing, we determined the
presence of early spliceosome assembly factors and snRNP complexes along the
ECM33 and ACT1 genes. We found that prp45(1-169) hampered the cotranscriptional
recruitment of U2 and, to a larger extent, U5 and NTC, while the U1 profile was
unaffected. The recruitment of Prp45(1-169) was impaired similarly to U5 snRNP
and NTC. Our results imply that Prp45 is required for timely formation of complex
A, prior to stable physical association of U5/NTC with the emerging pre-mRNA
substrate. We suggest that Prp45 facilitates conformational rearrangements and/or
contacts that couple U1 snRNP-recognition to downstream assembly events.
PMID- 28701520
TI - Ligand recognition and helical stacking formation are intimately linked in the
SAM-I riboswitch regulatory mechanism.
AB - Riboswitches are noncoding mRNA elements that control gene expression by altering
their structure upon metabolite binding. Although riboswitch crystal structures
provide detailed information about RNA-ligand interactions, little knowledge has
been gathered to understand how riboswitches modulate gene expression. Here, we
study the molecular recognition mechanism of the S-adenosylmethionine SAM-I
riboswitch by characterizing the formation of a helical stacking interaction
involving the ligand-binding process. We show that ligand binding is intimately
linked to the formation of the helical stacking, which is dependent on the
presence of three conserved purine residues that are flanked by stacked helices.
We also find that these residues are important for the formation of a crucial
long-range base pair formed upon SAM binding. Together, our results lend strong
support to a critical role for helical stacking in the folding pathway and
suggest a particularly important function in the formation of the long-range base
pair.
PMID- 28701522
TI - The yeast noncoding RNA interaction network.
AB - This article describes the creation of the first expert manually curated
noncoding RNA interaction networks for S. cerevisiae The RNA-RNA and RNA-protein
interaction networks have been carefully extracted from the experimental
literature and made available through the IntAct database (www.ebi.ac.uk/intact).
We provide an initial network analysis and compare their properties to the much
larger protein-protein interaction network. We find that the proteins that bind
to ncRNAs in the network contain only a small proportion of classical RNA binding
domains. We also see an enrichment of WD40 domains suggesting their direct
involvement in ncRNA interactions. We discuss the challenges in collecting
noncoding RNA interaction data and the opportunities for worldwide collaboration
to fill the unmet need for this data.
PMID- 28701521
TI - Translational repression of the Drosophila nanos mRNA involves the RNA helicase
Belle and RNA coating by Me31B and Trailer hitch.
AB - Translational repression of maternal mRNAs is an essential regulatory mechanism
during early embryonic development. Repression of the Drosophila nanos mRNA,
required for the formation of the anterior-posterior body axis, depends on the
protein Smaug binding to two Smaug recognition elements (SREs) in the nanos 3'
UTR. In a comprehensive mass spectrometric analysis of the SRE-dependent
repressor complex, we identified Smaug, Cup, Me31B, Trailer hitch, eIF4E, and
PABPC, in agreement with earlier data. As a novel component, the RNA-dependent
ATPase Belle (DDX3) was found, and its involvement in deadenylation and
repression of nanos was confirmed in vivo. Smaug, Cup, and Belle bound
stoichiometrically to the SREs, independently of RNA length. Binding of Me31B and
Tral was also SRE-dependent, but their amounts were proportional to the length of
the RNA and equimolar to each other. We suggest that "coating" of the RNA by a
Me31B*Tral complex may be at the core of repression.
PMID- 28701523
TI - Lifelong exercise, but not short-term high-intensity interval training, increases
GDF11, a marker of successful aging: a preliminary investigation.
AB - Lifelong exercise is associated with regulation of skeletal mass and function,
reductions in frailty, and successful aging. Yet, the influence of exercise on
myostatin and myostatin-interacting factors is relatively under examined in older
males. Therefore, we investigated whether serum total myostatin, free myostatin,
follistatin, and growth and differentiation factor 11 (GDF11) were altered
following high-intensity interval training (HIIT) in a group of 13 lifelong
sedentary (SED; 64 [6] years) and 11 lifelong exercising (LEX; 62 [6] years)
older males. SED follistatin was moderately greater than LEX pre-HIIT (Cohen's d
= 0.66), and was largely greater post-HIIT (Cohen's d = 1.22). The HIIT-induced
increase in follistatin was large in SED (Cohen's d = 0.82) and absent in LEX
(Cohen's d = 0.03). GDF11 was higher in LEX pre-HIIT (Cohen's d = 0.49) and post
HIIT (Cohen's d = 0.63) compared to SED HIIT resulted in no change to GDF11 in
LEX or SED (Cohen's d = 0.00-0.03). Peak power output and GDF11 were correlated
(r = 0.603), independent of grouping. Differences in GDF11 with lifelong exercise
training, paired with the correlation between GDF11 and peak power output,
suggested that GDF11 may be a relevant myostatin-interacting peptide to
successful aging in humans, and strategies to maintain this need to be further
explored.
PMID- 28701524
TI - Nanoparticles increase human bronchial epithelial cell susceptibility to
respiratory syncytial virus infection via nerve growth factor-induced autophagy.
AB - Cytotoxic and neuroinflammatory effects of TiO2 nanoparticles (TiO2-NP) in human
airways are mediated by nerve growth factor (NGF), which is also implicated in
the pathophysiology of respiratory syncytial virus (RSV) infection. We tested the
hypothesis that exposure to TiO2-NP results in increased susceptibility to RSV
infection and exacerbation of airway inflammation via NGF-mediated induction of
autophagy in lower respiratory tract cells. Human primary bronchial epithelial
cells were exposed to TiO2-NP for 24 h prior to infection with recombinant red
RSV (rrRSV). Expression of NGF and its TrkA and p75NTR receptors was measured by
real-time PCR and fluorescence-activated cell sorting (FACS). Autophagy was
assessed by beclin-1 expression analysis. Cell death was studied by FACS after
annexin V/propidium iodide staining. rrRSV infection efficiency more than doubled
in human bronchial cells pre-exposed to TiO2-NP compared to controls. NGF and its
TrkA receptor were upregulated in RSV-infected bronchial cells pre-exposed to
TiO2-NP compared to controls exposed to either rrRSV or TiO2-NP alone. Silencing
NGF gene expression with siRNA significantly inhibited rrRSV infection. rrRSV
infected cells pre-exposed to TiO2-NP also showed increase in necrotic cell death
and reduction in apoptosis, together with 4.3-fold increase in expression of the
early autophagosomal gene beclin-1. Pharmacological inhibition of beclin-1 by
wortmannin resulted in increased apoptotic rate along with lower viral load. This
study shows that TiO2-NP exposure enhances the infectivity of RSV in human
bronchial epithelial cells by upregulating the NGF/TrkA axis. The mechanism of
this interaction involves induction of autophagy promoting viral replication and
necrotic cell death.
PMID- 28701526
TI - How to Image Hypertrophic Cardiomyopathy.
PMID- 28701525
TI - Cigarette smoke differentially affects IL-13-induced gene expression in human
airway epithelial cells.
AB - Allergic airways inflammation in asthma is characterized by an airway epithelial
gene signature composed of POSTN, CLCA1, and SERPINB2 This Th2 gene signature is
proposed as a tool to classify patients with asthma into Th2-high and Th2-low
phenotypes. However, many asthmatics smoke and the effects of cigarette smoke
exposure on the epithelial Th2 gene signature are largely unknown. Therefore, we
investigated the combined effect of IL-13 and whole cigarette smoke (CS) on the
Th2 gene signature and the mucin-related genes MUC5AC and SPDEF in air-liquid
interface differentiated human bronchial (ALI-PBEC) and tracheal epithelial cells
(ALI-PTEC). Cultures were exposed to IL-13 for 14 days followed by 5 days of IL
13 with CS exposure. Alternatively, cultures were exposed once daily to CS for 14
days, followed by 5 days CS with IL-13. POSTN, SERPINB2, and CLCA1 expression
were measured 24 h after the last exposure to CS and IL-13. In both models POSTN,
SERPINB2, and CLCA1 expression were increased by IL-13. CS markedly affected the
IL-13-induced Th2 gene signature as indicated by a reduced POSTN, CLCA1, and
MUC5AC expression in both models. In contrast, IL-13-induced SERPINB2 expression
remained unaffected by CS, whereas SPDEF expression was additively increased.
Importantly, cessation of CS exposure failed to restore IL-13-induced POSTN and
CLCA1 expression. We show for the first time that CS differentially affects the
IL-13-induced gene signature for Th2-high asthma. These findings provide novel
insights into the interaction between Th2 inflammation and cigarette smoke that
is important for asthma pathogenesis and biomarker-guided therapy in asthma.
PMID- 28701527
TI - Relationship Between Myocardial Function, Body Mass Index, and Outcome After ST
Segment-Elevation Myocardial Infarction.
AB - BACKGROUND: Better survival for overweight and obese patients after ST-segment
elevation myocardial infarction (STEMI) has been demonstrated. The association
between body mass index (BMI), outcome, and left ventricular (LV) structure and
function after STEMI, including LV longitudinal strain (global longitudinal
strain), was evaluated. METHODS AND RESULTS: First patients with STEMI undergoing
primary percutaneous coronary intervention (n=1604; mean age, 61+/-12 years; 75%
men) had BMI measured on admission, and 2-dimensional transthoracic
echocardiography performed within 48 hours. Patients were categorized based on
standard criteria (normal/underweight, BMI<25 kg/m2 [n=486]; overweight,
25<=BMI<30 kg/m2 [n=820]; obese, BMI>=30 kg/m2 [n=298]). LV global longitudinal
strain was measured using speckle-tracking analysis. Primary outcome measure was
all-cause mortality. Compared with normal/underweight patients, obese patients
were younger and more likely to have diabetes mellitus, hypertension, and
hyperlipidemia and have higher discharge blood pressures. Despite no significant
differences in infarct size, obese patients had significantly more impaired LV
global longitudinal strain (-13.7+/-3.8 versus -15.0+/-4.2% and -15.0+/-4.1%;
P<0.001) compared with normal/underweight and overweight patients, respectively.
Although normal/underweight patients had the worst overall survival (log-rank
P=0.04) after STEMI during a median follow-up of 5.2 (3.6, 6.9) years on Kaplan
Meier analysis, a significant nonlinear association between BMI and all-cause
mortality across the range of BMI was seen, persisting after adjustment for age
and sex. CONCLUSIONS: Obese patients demonstrate greater adverse LV remodeling
and more impaired LV deformation after STEMI compared with those with normal BMI,
amid similar infarct characteristics. Normal weight patients continue to
demonstrate the worst survival, suggesting that the potential nonadverse effect
of higher BMI in this population is independent of LV function.
PMID- 28701528
TI - Blood Pressure and Arterial Load After Transcatheter Aortic Valve Replacement for
Aortic Stenosis.
AB - BACKGROUND: After aortic valve replacement, left ventricular afterload is often
characterized by the residual valve obstruction. Our objective was to determine
whether higher systemic arterial afterload-as reflected in blood pressure,
pulsatile and resistive load-is associated with adverse clinical outcomes after
transcatheter aortic valve replacement (TAVR). METHODS AND RESULTS: Total,
pulsatile, and resistive arterial load were measured in 2141 patients with severe
aortic stenosis treated with TAVR in the PARTNER I trial (Placement of Aortic
Transcatheter Valve) who had systolic blood pressure (SBP) and an echocardiogram
obtained 30 days after TAVR. The primary end point was 30-day to 1-year all-cause
mortality. Lower SBP at 30 days after TAVR was associated with higher mortality
(20.0% for SBP 100-129 mm Hg versus 12.0% for SBP 130-170 mm Hg; P<0.001). This
association remained significant after adjustment, was consistent across
subgroups, and confirmed in sensitivity analyses. In adjusted models that
included SBP, higher total and pulsatile arterial load were associated with
increased mortality (P<0.001 for all), but resistive load was not. Patients with
low 30-day SBP and high pulsatile load had a 3-fold higher mortality than those
with high 30-day SBP and low pulsatile load (26.1% versus 8.1%; hazard ratio,
3.62; 95% confidence interval, 2.36-5.55). CONCLUSIONS: Even after relief of
valve obstruction in patients with aortic stenosis, there is an independent
association between post-TAVR blood pressure, systemic arterial load, and
mortality. Blood pressure goals in patients with a history of aortic stenosis may
need to be redefined. Increased pulsatile arterial load, rather than blood
pressure, may be a target for adjunctive medical therapy to improve outcomes
after TAVR. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov.
Unique identifier: NCT00530894.
PMID- 28701529
TI - Blood Pressure, Arterial Load, and Survival After Transcatheter Aortic Valve
Replacement: Reducing the Gradient Is Only Part of the Picture.
PMID- 28701530
TI - The Good, the Bad, and the Ugly of Using Left Ventricular Longitudinal Myocardial
Deformation by Speckle-Tracking Echocardiography to Assess Patients After an
Acute Myocardial Infarction.
PMID- 28701531
TI - Differential contributions to the interception of occluded ballistic trajectories
by the temporoparietal junction, area hMT/V5+, and the intraparietal cortex.
AB - The ability to catch objects when transiently occluded from view suggests their
motion can be extrapolated. Intraparietal cortex (IPS) plays a major role in this
process along with other brain structures, depending on the task. For example,
interception of objects under Earth's gravity effects may depend on time-to
contact predictions derived from integration of visual signals processed by
hMT/V5+ with a priori knowledge of gravity residing in the temporoparietal
junction (TPJ). To investigate this issue further, we disrupted TPJ, hMT/V5+, and
IPS activities with transcranial magnetic stimulation (TMS) while subjects
intercepted computer-simulated projectile trajectories perturbed randomly with
either hypo- or hypergravity effects. In experiment 1, trajectories were occluded
either 750 or 1,250 ms before landing. Three subject groups underwent triple
pulse TMS (tpTMS, 3 pulses at 10 Hz) on one target area (TPJ | hMT/V5+ | IPS) and
on the vertex (control site), timed at either trajectory perturbation or
occlusion. In experiment 2, trajectories were entirely visible and participants
received tpTMS on TPJ and hMT/V5+ with same timing as experiment 1 tpTMS of TPJ,
hMT/V5+, and IPS affected differently the interceptive timing. TPJ stimulation
affected preferentially responses to 1-g motion, hMT/V5+ all response types, and
IPS stimulation induced opposite effects on 0-g and 2-g responses, being
ineffective on 1-g responses. Only IPS stimulation was effective when applied
after target disappearance, implying this area might elaborate memory
representations of occluded target motion. Results are compatible with the idea
that IPS, TPJ, and hMT/V5+ contribute to distinct aspects of visual motion
extrapolation, perhaps through parallel processing.NEW & NOTEWORTHY Visual
extrapolation represents a potential neural solution to afford motor interactions
with the environment in the face of missing information. We investigated relative
contributions by temporoparietal junction (TPJ), hMT/V5+, and intraparietal
cortex (IPS), cortical areas potentially involved in these processes. Parallel
organization of visual extrapolation processes emerged with respect to the
target's motion causal nature: TPJ was primarily involved for visual motion
congruent with gravity effects, IPS for arbitrary visual motion, whereas hMT/V5+
contributed at earlier processing stages.
PMID- 28701532
TI - Basal tree complexity shapes functional pathways in the prefrontal cortex.
AB - While the morphology of basal dendritic trees in cortical pyramidal neurons
varies, the functional implications of this diversity are just starting to
emerge. In layer 5 pyramidal neurons of the prefrontal cortex, for example,
increased basal tree complexity determines the recruitment of these neurons into
functional circuits. Here, we use a modeling approach to investigate whether and
how the morphology of the basal tree mediates the functional output of neurons.
We implemented 57 basal tree morphologies of layer 5 prefrontal pyramidal neurons
of the rat and identified morphological types that were characterized by
different response features, forming distinct functional types. These types were
robust to a wide range of manipulations (distribution of active ionic mechanisms,
NMDA conductance, somatic and apical tree morphology, or the number of activated
synapses) and supported different temporal coding schemes at both the single
neuron and the microcircuit level. We predict that the basal tree morphological
diversity among neurons of the same class mediates their segregation into
distinct functional pathways. Extension of our approach/findings to other
cortical areas and/or layers or under pathological conditions may provide a
generalized role of the basal trees for neuronal function.NEW & NOTEWORTHY Our
results suggest that the segregation of neurons to different functional types
based on their basal tree morphology is in large part independent of the
distribution of active ionic mechanisms, NMDA conductance, somatic and apical
tree morphology, and the number of activated synapses; different functional types
support distinct temporal coding schemes. This can be exploited to create
networks with diverse coding characteristics, thus contributing to the functional
heterogeneity within the same layer and area.
PMID- 28701533
TI - Treadmill vs. overground walking: different response to physical interaction.
AB - Rehabilitation of human motor function is an issue of growing significance, and
human-interactive robots offer promising potential to meet the need. For the
lower extremity, however, robot-aided therapy has proven challenging. To inform
effective approaches to robotic gait therapy, it is important to better
understand unimpaired locomotor control: its sensitivity to different mechanical
contexts and its response to perturbations. The present study evaluated the
behavior of 14 healthy subjects who walked on a motorized treadmill and
overground while wearing an exoskeletal ankle robot. Their response to a periodic
series of ankle plantar flexion torque pulses, delivered at periods different
from, but sufficiently close to, their preferred stride cadence, was assessed to
determine whether gait entrainment occurred, how it differed across conditions,
and if the adapted motor behavior persisted after perturbation. Certain aspects
of locomotor control were exquisitely sensitive to walking context, while others
were not. Gaits entrained more often and more rapidly during overground walking,
yet, in all cases, entrained gaits synchronized the torque pulses with ankle push
off, where they provided assistance with propulsion. Furthermore, subjects
entrained to perturbation periods that required an adaption toward slower
cadence, even though the pulses acted to accelerate gait, indicating a neural
adaptation of locomotor control. Lastly, during 15 post-perturbation strides, the
entrained gait period was observed to persist more frequently during overground
walking. This persistence was correlated with the number of strides walked at the
entrained gait period (i.e., longer exposure), which also indicated a neural
adaptation.NEW & NOTEWORTHY We show that the response of human locomotion to
physical interaction differs between treadmill and overground walking. Subjects
entrained to a periodic series of ankle plantar flexion torque pulses that
shifted their gait cadence, synchronizing ankle push-off with the pulses (so that
they assisted propulsion) even when gait cadence slowed. Entrainment was faster
overground and, on removal of torque pulses, the entrained gait period persisted
more prominently overground, indicating a neural adaptation of locomotor control.
PMID- 28701534
TI - Compensating for intersegmental dynamics across the shoulder, elbow, and wrist
joints during feedforward and feedback control.
AB - Moving the arm is complicated by mechanical interactions that arise between limb
segments. Such intersegmental dynamics cause torques applied at one joint to
produce movement at multiple joints, and in turn, the only way to create single
joint movement is by applying torques at multiple joints. We investigated whether
the nervous system accounts for intersegmental limb dynamics across the shoulder,
elbow, and wrist joints during self-initiated planar reaching and when countering
external mechanical perturbations. Our first experiment tested whether the timing
and amplitude of shoulder muscle activity account for interaction torques
produced during single-joint elbow movements from different elbow initial
orientations and over a range of movement speeds. We found that shoulder muscle
activity reliably preceded movement onset and elbow agonist activity, and was
scaled to compensate for the magnitude of interaction torques arising because of
forearm rotation. Our second experiment tested whether elbow muscles compensate
for interaction torques introduced by single-joint wrist movements. We found that
elbow muscle activity preceded movement onset and wrist agonist muscle activity,
and thus the nervous system predicted interaction torques arising because of hand
rotation. Our third and fourth experiments tested whether shoulder muscles
compensate for interaction torques introduced by different hand orientations
during self-initiated elbow movements and to counter mechanical perturbations
that caused pure elbow motion. We found that the nervous system predicted the
amplitude and direction of interaction torques, appropriately scaling the
amplitude of shoulder muscle activity during self-initiated elbow movements and
rapid feedback control. Taken together, our results demonstrate that the nervous
system robustly accounts for intersegmental dynamics and that the process is
similar across the proximal to distal musculature of the arm as well as between
feedforward (i.e., self-initiated) and feedback (i.e., reflexive) control.NEW &
NOTEWORTHY Intersegmental dynamics complicate the mapping between applied joint
torques and the resulting joint motions. We provide evidence that the nervous
system robustly predicts these intersegmental limb dynamics across the shoulder,
elbow, and wrist joints during reaching and when countering external
perturbations.
PMID- 28701535
TI - Enhancement of phase-locking in rodents. I. An axonal recording study in gerbil.
AB - The trapezoid body (TB) contains axons of neurons in the anteroventral cochlear
nucleus projecting to monaural and binaural nuclei in the superior olivary
complex (SOC). Characterization of these monaural inputs is important for the
interpretation of response properties of SOC neurons. In particular,
understanding of the sensitivity to interaural time differences (ITDs) in neurons
of the medial and lateral superior olive requires knowledge of the temporal
firing properties of the monaural excitatory and inhibitory inputs to these
neurons. In recent years, studies of ITD sensitivity of SOC neurons have made
increasing use of small animal models with good low-frequency hearing,
particularly the gerbil. We presented stimuli as used in binaural studies to
monaural neurons in the TB and studied their temporal coding. We found that
general trends as have been described in the cat are present in gerbil, but with
some important differences. Phase-locking to pure tones tends to be higher in TB
axons and in neurons of the medial nucleus of the TB (MNTB) than in the auditory
nerve for neurons with characteristic frequencies (CFs) below 1 kHz, but this
enhancement is quantitatively more modest than in cat. Stronger enhancement is
common when TB neurons are stimulated at low frequencies below CF. It is rare for
TB neurons in gerbil to entrain to low-frequency stimuli, i.e., to discharge a
well-timed spike on every stimulus cycle. Also, complex phase-locking behavior,
with multiple modes of increased firing probability per stimulus cycle, is common
in response to low frequencies below CF.NEW & NOTEWORTHY Phase-locking is an
important property of neurons in the early auditory pathway: it is critical for
the sensitivity to time differences between the two ears enabling spatial
hearing. Studies in cat have shown an improvement in phase-locking from the
peripheral to the central auditory nervous system. We recorded from axons in an
output tract of the cochlear nucleus and show that a similar but more limited
form of temporal enhancement is present in gerbil.
PMID- 28701536
TI - Spatially tuned normalization explains attention modulation variance within
neurons.
AB - Spatial attention improves perception of attended parts of a scene, a behavioral
enhancement accompanied by modulations of neuronal firing rates. These
modulations vary in size across neurons in the same brain area. Models of
normalization explain much of this variance in attention modulation with
differences in tuned normalization across neurons (Lee J, Maunsell JHR. PLoS One
4: e4651, 2009; Ni AM, Ray S, Maunsell JHR. Neuron 73: 803-813, 2012). However,
recent studies suggest that normalization tuning varies with spatial location
both across and within neurons (Ruff DA, Alberts JJ, Cohen MR. J Neurophysiol
116: 1375-1386, 2016; Verhoef BE, Maunsell JHR. eLife 5: e17256, 2016). Here we
show directly that attention modulation and normalization tuning do in fact
covary within individual neurons, in addition to across neurons as previously
demonstrated. We recorded the activity of isolated neurons in the middle temporal
area of two rhesus monkeys as they performed a change-detection task that
controlled the focus of spatial attention. Using the same two drifting Gabor
stimuli and the same two receptive field locations for each neuron, we found that
switching which stimulus was presented at which location affected both attention
modulation and normalization in a correlated way within neurons. We present an
equal-maximum-suppression spatially tuned normalization model that explains this
covariance both across and within neurons: each stimulus generates equally strong
suppression of its own excitatory drive, but its suppression of distant stimuli
is typically less. This new model specifies how the tuned normalization
associated with each stimulus location varies across space both within and across
neurons, changing our understanding of the normalization mechanism and how
attention modulations depend on this mechanism.NEW & NOTEWORTHY Tuned
normalization studies have demonstrated that the variance in attention modulation
size seen across neurons from the same cortical area can be largely explained by
between-neuron differences in normalization strength. Here we demonstrate that
attention modulation size varies within neurons as well and that this variance is
largely explained by within-neuron differences in normalization strength. We
provide a new spatially tuned normalization model that explains this broad range
of observed normalization and attention effects.
PMID- 28701537
TI - Climbing fibers predict movement kinematics and performance errors.
AB - Requisite for understanding cerebellar function is a complete characterization of
the signals provided by complex spike (CS) discharge of Purkinje cells, the
output neurons of the cerebellar cortex. Numerous studies have provided insights
into CS function, with the most predominant view being that they are evoked by
error events. However, several reports suggest that CSs encode other aspects of
movements and do not always respond to errors or unexpected perturbations. Here,
we evaluated CS firing during a pseudo-random manual tracking task in the monkey
(Macaca mulatta). This task provides extensive coverage of the work space and
relative independence of movement parameters, delivering a robust data set to
assess the signals that activate climbing fibers. Using reverse correlation, we
determined feedforward and feedback CSs firing probability maps with position,
velocity, and acceleration, as well as position error, a measure of tracking
performance. The direction and magnitude of the CS modulation were quantified
using linear regression analysis. The major findings are that CSs significantly
encode all three kinematic parameters and position error, with acceleration
modulation particularly common. The modulation is not related to "events," either
for position error or kinematics. Instead, CSs are spatially tuned and provide a
linear representation of each parameter evaluated. The CS modulation is largely
predictive. Similar analyses show that the simple spike firing is modulated by
the same parameters as the CSs. Therefore, CSs carry a broader array of signals
than previously described and argue for climbing fiber input having a prominent
role in online motor control.NEW & NOTEWORTHY This article demonstrates that
complex spike (CS) discharge of cerebellar Purkinje cells encodes multiple
parameters of movement, including motor errors and kinematics. The CS firing is
not driven by error or kinematic events; instead it provides a linear
representation of each parameter. In contrast with the view that CSs carry
feedback signals, the CSs are predominantly predictive of upcoming position
errors and kinematics. Therefore, climbing fibers carry multiple and predictive
signals for online motor control.
PMID- 28701538
TI - Differential expression of long-term potentiation among identified inhibitory
inputs to dopamine neurons.
AB - The in vivo firing pattern of ventral tegmental area (VTA) dopamine neurons is
controlled by GABA afferents originating primarily from the nucleus accumbens
(NAc), rostromedial tegmental nucleus (RMTg), and local GABA neurons within the
VTA. Although different forms of plasticity have been observed from GABA inputs
to VTA dopamine neurons, one dependent on cyclic GMP synthesis and the other on
adenylyl cyclase activation, it is unknown whether plasticity is differentially
expressed in each. Using an optogenetic strategy, we show that identified
inhibitory postsynaptic currents (IPSCs) from local VTA GABA neurons and NAc
afferents exhibit a cyclic GMP-dependent long-term potentiation (LTP) that is
capable of inhibiting the firing activity of dopamine neurons. However, this form
of LTP was not induced from RMTg afferents. Only an adenylyl cyclase-mediated
increase in IPSCs was exhibited by all three inputs. Thus discrete plasticity
mechanisms recruit overlapping but different subsets of GABA inputs to VTA
dopamine neurons.NEW & NOTEWORTHY We describe a mapping of plasticity expression,
mediated by different mechanisms, among three distinct GABA afferents to ventral
tegmental area (VTA) dopamine neurons: the rostromedial tegmental nucleus, the
nucleus accumbens, and the local GABA neurons within the VTA known to synapse on
VTA dopamine neurons. This work is the first demonstration that discrete
plasticity mechanisms recruit overlapping but different subsets of GABA inputs to
VTA dopamine neurons.
PMID- 28701539
TI - Measuring and quantifying skin sympathetic nervous system activity in humans.
AB - Development of the technique of microneurography has substantially increased our
understanding of the function of the sympathetic nervous system (SNS) in health
and in disease. The ability to directly record signals from peripheral autonomic
nerves in conscious humans allows for qualitative and quantitative
characterization of SNS responses to specific stimuli and over time. Furthermore,
distinct neural outflow to muscle (MSNA) and skin (SSNA) can be delineated.
However, there are limitations and caveats to the use of microneurography,
measurement criteria, and signal analysis and interpretation. MSNA recordings
have a longer history and are considered relatively more straightforward from a
measurement and analysis perspective. This brief review provides an overview of
the development of the technique as used to measure SSNA. The focus is on the
utility of measuring sympathetic activity directed to the skin, the unique issues
related to analyzing and quantifying multiunit SSNA, and the challenges related
to its interpretation.
PMID- 28701540
TI - A novel paraplegia model in awake behaving macaques.
AB - Lower limb paralysis from spinal cord injury (SCI) or neurological disease
carries a poor prognosis for recovery and remains a large societal burden.
Neurophysiological and neuroprosthetic research have the potential to improve
quality of life for these patients; however, the lack of an ethical and
sustainable nonhuman primate model for paraplegia hinders their advancement.
Therefore, our multidisciplinary team developed a way to induce temporary
paralysis in awake behaving macaques by creating a fully implantable lumbar
epidural catheter-subcutaneous port system that enables easy and reliable
targeted drug delivery for sensorimotor blockade. During treadmill walking,
aliquots of 1.5% lidocaine with 1:200,000 epinephrine were percutaneously
injected into the ports of three rhesus macaques while surface electromyography
(EMG) recorded muscle activity from their quadriceps and gastrocnemii. Diminution
of EMG amplitude, loss of voluntary leg movement, and inability to bear weight
were achieved for 60-90 min in each animal, followed by a complete recovery of
function. The monkeys remained alert and cooperative during the paralysis trials
and continued to take food rewards, and the ports remained functional after
several months. This technique will enable recording from the cortex and/or
spinal cord in awake behaving nonhuman primates during the onset, maintenance,
and resolution of paraplegia for the first time, thus opening the door to
answering basic neurophysiological questions about the acute neurological
response to spinal cord injury and recovery. It will also negate the need to
permanently injure otherwise high-value research animals for certain experimental
paradigms aimed at developing and testing neural interface decoding algorithms
for patients with lower extremity dysfunction.NEW & NOTEWORTHY A novel
implantable lumbar epidural catheter-subcutaneous port system enables targeted
drug delivery and induction of temporary paraplegia in awake, behaving nonhuman
primates. Three macaques displayed loss of voluntary leg movement for 60-90 min
after injection of lidocaine with epinephrine, followed by a full recovery. This
technique for the first time will enable ethical live recording from the proximal
central nervous system during the acute onset, maintenance, and resolution of
paraplegia.
PMID- 28701541
TI - Afferent input and sensory function after human spinal cord injury.
AB - Spinal cord injury (SCI) often disrupts the integrity of afferent (sensory) axons
projecting through the spinal cord dorsal columns to the brain. Examinations of
ascending sensory tracts, therefore, are critical for monitoring the extent of
SCI and recovery processes. In this review, we discuss the most common
electrophysiological techniques used to assess transmission of afferent inputs to
the primary motor cortex (i.e., afferent input-induced facilitation and
inhibition) and the somatosensory cortex [i.e., somatosensory evoked potentials
(SSEPs), dermatomal SSEPs, and electrical perceptual thresholds] following human
SCI. We discuss how afferent input modulates corticospinal excitability by
involving cortical and spinal mechanisms depending on the timing of the effects,
which need to be considered separately for upper and lower limb muscles. We argue
that the time of arrival of afferent input onto the sensory and motor cortex is
critical to consider in plasticity-induced protocols in humans with SCI. We also
discuss how current sensory exams have been used to detect differences between
control and SCI participants but might be less optimal to characterize the level
and severity of injury. There is a need to conduct some of these
electrophysiological examinations during functionally relevant behaviors to
understand the contribution of impaired afferent inputs to the control, or lack
of control, of movement. Thus the effects of transmission of afferent inputs to
the brain need to be considered on multiple functions following human SCI.
PMID- 28701542
TI - Group IV nociceptors develop axonal chemical sensitivity during neuritis and
following treatment of the sciatic nerve with vinblastine.
AB - We have previously shown that nerve inflammation (neuritis) and transient
vinblastine application lead to axonal mechanical sensitivity in nociceptors
innervating deep structures. We also have shown that these treatments reduce
axonal transport and have proposed that this leads to functional accumulation of
mechanically sensitive channels in the affected part of the axons. Though
informing the etiology of mechanically induced pain, axonal mechanical
sensitivity does not address the common report of ongoing radiating pain during
neuritis, which could be secondary to the provocation of axonal chemical
sensitivity. We proposed that neuritis and vinblastine application would induce
sensitivities to noxious chemicals and that the number of chemo-sensitive
channels would be increased at the affected site. In adult female rats, nerves
were either untreated or treated with complete Freund's adjuvant (to induce
neuritis) or vinblastine. After 3-7 days, dorsal root teased fiber recordings
were taken from group IV neurons with axons within the sciatic nerve. Sciatic
nerves were injected intraneurally with a combination of noxious inflammatory
chemicals. Whereas no normal sciatic axons responded to this stimulus, 80% and
38% of axons responded in the neuritis and vinblastine groups, respectively. In
separate experiments, sciatic nerves were partially ligated and treated with
complete Freund's adjuvant or vinblastine (with controls), and after 3-5 days
were immunolabeled for the histamine H3 receptor. The results support that both
neuritis and vinblastine treatment reduce transport of the histamine H3 receptor.
The finding that nociceptor axons can develop ectopic chemical sensitivity is
consistent with ongoing radiating pain due to nerve inflammation.NEW & NOTEWORTHY
Many patients suffer ongoing pain with no local pathology or apparent nerve
injury. We show that nerve inflammation and transient application of vinblastine
induce sensitivity of group IV nociceptor axons to a mixture of endogenous
inflammatory chemicals. We also show that the same conditions reduce the axonal
transport of the histamine H3 receptor. The results provide a mechanism for
ongoing nociception from focal nerve inflammation or pressure without overt nerve
damage.
PMID- 28701543
TI - Novel channel-mediated choline transport in cholinergic neurons of the mouse
retina.
AB - Choline uptake into the presynaptic terminal of cholinergic neurons is mediated
by the high-affinity choline transporter and is essential for acetylcholine
synthesis. In a previous study, we reported that P2X2 purinoceptors are
selectively expressed in OFF-cholinergic amacrine cells of the mouse retina.
Under specific conditions, P2X2 purinoceptors acquire permeability to large
cations, such as N-methyl-d-glucamine, and therefore potentially could act as a
noncanonical pathway for choline entry into neurons. We tested this hypothesis in
OFF-cholinergic amacrine cells of the mouse retina. ATP-induced choline currents
were observed in OFF-cholinergic amacrine cells, but not in ON-cholinergic
amacrine cells, in mouse retinal slice preparations. High-affinity choline
transporters are expressed at higher levels in ON-cholinergic amacrine cells than
in OFF-cholinergic amacrine cells. In dissociated preparations of cholinergic
amacrine cells, ATP-activated cation currents arose from permeation of
extracellular choline. We also examined the pharmacological properties of choline
currents. Pharmacologically, alpha,beta-methylene ATP did not produce a cation
current, whereas ATPgammaS and benzoyl-benzoyl-ATP (BzATP) activated choline
currents. However, the amplitude of the choline current activated by BzATP was
very small. The choline current activated by ATP was strongly inhibited by
pyridoxalphosphate-6-azophenyl-2',4'-sulfonic acid. Accordingly, P2X2
purinoceptors expressed in HEK-293T cells were permeable to choline and similarly
functioned as a choline uptake pathway. Our physiological and pharmacological
findings support the hypothesis that P2 purinoceptors, including P2X2
purinoceptors, function as a novel choline transport pathway and may provide a
new regulatory mechanism for cholinergic signaling transmission at synapses in
OFF-cholinergic amacrine cells of the mouse retina.NEW & NOTEWORTHY Choline
transport across the membrane is exerted by both the high-affinity and low
affinity choline transporters. We found that choline can permeate P2 purinergic
receptors, including P2X2 purinoceptors, in cholinergic neurons of the retina.
Our findings show the presence of a novel choline transport pathway in
cholinergic neurons. Our findings also indicate that the permeability of P2X2
purinergic receptors to choline observed in the heterologous expression system
may have a physiological relevance in vivo.
PMID- 28701544
TI - Modulation of corticospinal input to the legs by arm and leg cycling in people
with incomplete spinal cord injury.
AB - The spinal cervico-lumbar interaction during rhythmic movements in humans has
recently been studied; however, the role of arm movements in modulating the
corticospinal drive to the legs is not well understood. The goals of this study
were to investigate the effect of active rhythmic arm movements on the
corticospinal drive to the legs (study 1) and assess the effect of simultaneous
arm and leg training on the corticospinal pathway after incomplete spinal cord
injury (iSCI) (study 2). In study 1, neurologically intact (NI) participants or
participants with iSCI performed combinations of stationary and rhythmic cycling
of the arms and legs while motor evoked potentials (MEPs) were recorded from the
vastus lateralis (VL) muscle. In the NI group, arm cycling alone could facilitate
the VL MEP amplitude, suggesting that dynamic arm movements strongly modulate the
corticospinal pathway to the legs. No significant difference in VL MEP between
conditions was found in participants with iSCI. In study 2, participants with
iSCI underwent 12 wk of electrical stimulation-assisted cycling training: one
group performed simultaneous arm and leg (A&L) cycling and the other legs-only
cycling. MEPs in the tibialis anterior (TA) muscle were compared before and after
training. After training, only the A&L group had a significantly larger TA MEP,
suggesting increased excitability in the corticospinal pathway. The findings
demonstrate the importance of arm movements in modulating the corticospinal drive
to the legs and suggest that active engagement of the arms in lower limb
rehabilitation may produce better neural regulation and restoration of
function.NEW & NOTEWORTHY This study aimed to demonstrate the importance of arm
movements in modulating the corticospinal drive to the legs. It provides direct
evidence in humans that active movement of the arms could facilitate
corticospinal transmission to the legs and, for the first time, shows that
facilitation is absent after spinal cord injury. Active engagement of the arms in
lower limb rehabilitation increased the excitability of the corticospinal pathway
and may produce more effective improvement in leg function.
PMID- 28701545
TI - Decoding sound level in the marmoset primary auditory cortex.
AB - Neurons that respond favorably to a particular sound level have been observed
throughout the central auditory system, becoming steadily more common at higher
processing areas. One theory about the role of these level-tuned or nonmonotonic
neurons is the level-invariant encoding of sounds. To investigate this theory, we
simulated various subpopulations of neurons by drawing from real primary auditory
cortex (A1) neuron responses and surveyed their performance in forming different
sound level representations. Pure nonmonotonic subpopulations did not provide the
best level-invariant decoding; instead, mixtures of monotonic and nonmonotonic
neurons provided the most accurate decoding. For level-fidelity decoding, the
inclusion of nonmonotonic neurons slightly improved or did not change decoding
accuracy until they constituted a high proportion. These results indicate that
nonmonotonic neurons fill an encoding role complementary to, rather than
alternate to, monotonic neurons.NEW & NOTEWORTHY Neurons with nonmonotonic rate
level functions are unique to the central auditory system. These level-tuned
neurons have been proposed to account for invariant sound perception across sound
levels. Through systematic simulations based on real neuron responses, this study
shows that neuron populations perform sound encoding optimally when containing
both monotonic and nonmonotonic neurons. The results indicate that instead of
working independently, nonmonotonic neurons complement the function of monotonic
neurons in different sound-encoding contexts.
PMID- 28701546
TI - Fast voltage-sensitive dye imaging of excitatory and inhibitory synaptic
transmission in the rat granular retrosplenial cortex.
AB - Rodent granular retrosplenial cortex (GRS) has dense connections between the
anterior thalamic nuclei (ATN) and hippocampal formation. GRS superficial
pyramidal neurons exhibit distinctive late spiking (LS) firing property and form
patchy clusters with prominent apical dendritic bundles. The aim of this study
was to investigate spatiotemporal dynamics of signal transduction in the GRS
induced by ATN afferent stimulation by using fast voltage-sensitive dye imaging
in rat brain slices. In coronal slices, layer 1a stimulation, which presumably
activated thalamic fibers, evoked propagation of excitatory synaptic signals from
layers 2-4 to layers 5-6 in a direction perpendicular to the layer axis, followed
by transverse signal propagation within each layer. In the presence of ionotropic
glutamate receptor antagonists, inhibitory responses were observed in superficial
layers, induced by direct activation of inhibitory interneurons in layer 1. In
horizontal slices, excitatory signals in deep layers propagated transversely
mainly from posterior to anterior via superficial layers. Cortical inhibitory
responses upon layer 1a stimulation in horizontal slices were weaker than those
in the coronal slices. Observed differences between coronal and horizontal planes
suggest anisotropy of the intracortical circuitry. In conclusion, ATN inputs are
processed differently in coronal and horizontal planes of the GRS and then
conveyed to other cortical areas. In both planes, GRS superficial layers play an
important role in signal propagation, which suggests that superficial neuronal
cascade is crucial in the integration of multiple information sources.NEW &
NOTEWORTHY Superficial neurons in the rat granular retrosplenial cortex (GRS)
show distinctive late-spiking (LS) firing property. However, little is known
about spatiotemporal dynamics of signal transduction in the GRS. We demonstrated
LS neuron network relaying thalamic inputs to deep layers and anisotropic
distribution of inhibition between coronal and horizontal planes. Since deep
layers of the GRS receive inputs from the subiculum, GRS circuits may work as an
integrator of multiple sources such as sensory and memory information.
PMID- 28701547
TI - Aging does not affect the intralimb coordination elicited by slip-like
perturbation of different intensities.
AB - This study was aimed at verifying whether aging modifies intralimb coordination
strategy during corrective responses elicited by unexpected slip-like
perturbations delivered during steady walking on a treadmill. To this end, 10
young and 10 elderly subjects were asked to manage unexpected slippages of
different intensities. We analyzed the planar covariation law of the lower limb
segments, using the principal component analysis, to verify whether elevation
angles of older subjects covaried along a plan before and after the perturbation.
Results showed that segments related to the perturbed limbs of both younger and
older people do not covary after all perturbations. Conversely, the planar
covariation law of the unperturbed limb was systematically held for younger and
older subjects. These results occurred despite differences in spatio-temporal and
kinematic parameters being observed among groups and perturbation intensities.
Overall, our analysis revealed that aging does not affect intralimb coordination
during corrective responses induced by slip-like perturbation, suggesting that
both younger and older subjects adopt this control strategy while managing sudden
and unexpected postural transitions of increasing intensities. Accordingly,
results corroborate the hypothesis that balance control emerges from a governing
set of biomechanical invariants, that is, suitable control schemes (e.g., planar
covariation law) shared across voluntary and corrective motor behaviors, and
across different sensory contexts due to different perturbation intensities, in
both younger and older subjects. In this respect, our findings provide further
support to investigate the effects of specific task training programs to
counteract the risk of fall.NEW & NOTEWORTHY This study was aimed at
investigating how aging affects the intralimb coordination of lower limb
segments, described by the planar covariation law, during unexpected slip-like
perturbations of increasing intensity. Results revealed that neither the aging
nor the perturbation intensity affects this coordination strategy. Accordingly,
we proposed that the balance control emerges from an invariant set of control
schemes shared across different sensory motor contexts and despite age-related
neuromuscular adaptations.
PMID- 28701548
TI - Intermittent cortical involvement in the preservation of tremor in essential
tremor.
AB - Cortical involvement in essential tremor, an involuntary action tremor supposedly
of subcortical origin, is uncertain. Conflicting results of corticomuscular
coherence studies in essential tremor suggest an intermittent corticomuscular
coupling. On the basis of the literature, we hypothesized that corticomuscular
coupling is influenced by bilateral motor synchronization and "cognitive states"
such as awareness of tremor. In the present study, we investigated 1) the
existence of intermittent corticomuscular coherence (CMC) in essential tremor and
2) factors that influence CMC strength. In 18 essential tremor patients and 18
healthy controls, who mimicked tremor, we simultaneously recorded 64-channel EEG
and 6-channel bipolar surface EMG from right and left wrist extensors and
flexors. Right-sided (mimicked) hand tremor was recorded with and without a
cognitive arithmetic task and with left-sided (mimicked) hand tremor. CMC values
per task were compared within and between groups. Changes in CMC strength during
tasks were calculated. Our main findings are 1) significant CMC around the
(mimicked) tremor frequency across all tasks in both groups; 2) significant
differences in CMC between unilateral tasks, with the highest values during the
cognitive task only in the essential tremor group; and 3) significant
fluctuations of CMC strength over time, independent of the tremor intensity, only
in the essential tremor group. Our results suggest a limited role, and certainly
not a continuous steering role, of sensorimotor cortical neurons in the
generation of tremor. In clinical practice, these findings might help to
standardize tremor registration and the interpretation of the analysis.NEW &
NOTEWORTHY The part of the motor cortex involved in essential tremor is
uncertain. The current electrophysiological study is the first to assess
corticomuscular coherence systematically. The study shows a dynamic nature of
corticomuscular coherence and a possible influence of cognitive states. The
results elucidate the involvement of the motor cortex in tremor and help
interpret the varying results in the literature. In clinical practice, the
findings may guide in standardizing tremor registration and its interpretation.
PMID- 28701549
TI - Altered visual strategies and attention are related to increased force
fluctuations during a pinch grip task in older adults.
AB - The purpose of the study was to determine the visual strategies used by older
adults during a pinch grip task and to assess the relations between visual
strategy, deficits in attention, and increased force fluctuations in older
adults. Eye movements of 23 older adults (>65 yr) were monitored during a low
force pinch grip task while subjects viewed three common visual feedback
displays. Performance on the Grooved Pegboard test and an attention task (which
required no concurrent hand movements) was also measured. Visual strategies
varied across subjects and depended on the type of visual feedback provided to
the subjects. First, while viewing a high-gain compensatory feedback display
(horizontal bar moving up and down with force), 9 of 23 older subjects adopted a
strategy of performing saccades during the task, which resulted in 2.5 times
greater force fluctuations in those that exhibited saccades compared with those
who maintained fixation near the target line. Second, during pursuit feedback
displays (force trace moving left to right across screen and up and down with
force), all subjects exhibited multiple saccades, and increased force
fluctuations were associated (rs = 0.6; P = 0.002) with fewer saccades during the
pursuit task. Also, decreased low-frequency (<4 Hz) force fluctuations and
Grooved Pegboard times were significantly related (P = 0.033 and P = 0.005,
respectively) with higher (i.e., better) attention z scores. Comparison of these
results with our previously published results in young subjects indicates that
saccadic eye movements and attention are related to force control in older
adults.NEW & NOTEWORTHY The significant contributions of the study are the
addition of eye movement data and an attention task to explain differences in
hand motor control across different visual displays in older adults. Older
participants used different visual strategies across varying feedback displays,
and saccadic eye movements were related with motor performance. In addition,
those older individuals with deficits in attention had impaired motor performance
on two different hand motor control tasks, including the Grooved Pegboard test.
PMID- 28701550
TI - Influence of envelope waveform on ITD sensitivity of neurons in the auditory
midbrain.
AB - Interaural time differences (ITDs) conveyed by the modulated envelopes of high
frequency sounds can serve as a cue for localizing a sound source. Klein-Hennig
et al. (J Acoust Soc Am 129: 3856, 2011) demonstrated the envelope attack (the
rate at which stimulus energy in the envelope increases) and the duration of the
pause (the interval between successive envelope pulses) as important factors
affecting sensitivity to envelope ITDs in human listeners. Modulated sounds with
rapid attacks and long pauses produce the lowest ITD discrimination thresholds.
The duration of the envelope's sustained component (sustain) and the rate at
which stimulus energy falls at the offset of the envelope (decay) are only minor
factors. We assessed the responses of 71 single neurons, recorded from the
midbrains of 15 urethane-anesthetized tri-colored guinea pigs, to envelope shapes
in which the four envelope components, i.e., attack, sustain, decay, and pause,
were systematically varied. We confirmed the importance of the attack and pause
components in generating ITD-sensitive responses. Analysis of neural firing rates
demonstrated more neurons (49/71) show ITD sensitivity in response to "damped"
stimuli (fast attack and slow decay) compared with "ramped" stimuli (slow attack
and fast decay) (14/71). Furthermore, the lowest threshold for the damped
stimulus (91 MUs) was lower by a factor of 4 than that for the temporally
reversed ramped envelope shape (407 MUs). The data confirm the importance of fast
attacks and optimal pause durations in generating sensitivity to ITDs conveyed in
the modulated envelopes of high-frequency sounds and are incompatible with models
of ITD processing based on the integration of sound energy over time.NEW &
NOTEWORTHY Using single-neuron electrophysiology, we show that the precise shape
of a sound's "energy envelope" is a critical factor in determining how well
midbrain neurons are able to convey information about auditory spatial cues.
Consistent with human behavioral performance, sounds with rapidly rising energy
and relatively long intervals between energy bursts are best at conveying spatial
information. The data suggest specific sound energy patterns that might best be
applied to hearing devices to aid spatial listening.
PMID- 28701551
TI - Classic Spotlight, 1996 and 1997: Articles of Significant Interest Selected from
the Journal of Virology Archives by the Editors.
PMID- 28701553
TI - Walking like an ant: a quantitative and experimental approach to understanding
locomotor mimicry in the jumping spider Myrmarachne formicaria.
AB - Protective mimicry, in which a palatable species avoids predation by being
mistaken for an unpalatable model, is a remarkable example of adaptive evolution.
These complex interactions between mimics, models and predators can explain
similarities between organisms beyond the often-mechanistic constraints typically
invoked in studies of convergent evolution. However, quantitative studies of
protective mimicry typically focus on static traits (e.g. colour and shape)
rather than on dynamic traits like locomotion. Here, we use high-speed cameras
and behavioural experiments to investigate the role of locomotor behaviour in
mimicry by the ant-mimicking jumping spider Myrmarachne formicaria, comparing its
movement to that of ants and non-mimicking spiders. Contrary to previous
suggestions, we find mimics walk using all eight legs, raising their forelegs
like ant antennae only when stationary. Mimics exhibited winding trajectories
(typical wavelength = 5-10 body lengths), which resemble the winding patterns of
ants specifically engaged in pheromone-trail following, although mimics walked on
chemically inert surfaces. Mimics also make characteristically short (approx. 100
ms) pauses. Our analysis suggests that this makes mimics appear ant-like to
observers with slow visual systems. Finally, behavioural experiments with
predatory spiders yield results consistent with the protective mimicry
hypothesis. These findings highlight the importance of dynamic behaviours and
observer perception in mimicry.
PMID- 28701554
TI - Evolution of ageing, costs of reproduction and the fecundity-longevity trade-off
in eusocial insects.
AB - Eusocial insects provide special opportunities to elucidate the evolution of
ageing as queens have apparently evaded costs of reproduction and reversed the
fecundity-longevity trade-off generally observed in non-social organisms. But how
reproduction affects longevity in eusocial insects has rarely been tested
experimentally. In this study, we took advantage of the reproductive plasticity
of workers to test the causal role of reproduction in determining longevity in
eusocial insects. Using the eusocial bumblebee Bombus terrestris, we found that,
in whole colonies, in which workers could freely 'choose' whether to become
reproductive, workers' level of ovarian activation was significantly positively
associated with longevity and ovary-active workers significantly outlived ovary
inactive workers. By contrast, when reproductivity was experimentally induced in
randomly selected workers, thereby decoupling it from other traits, workers'
level of ovarian activation was significantly negatively associated with
longevity and ovary-active workers were significantly less long-lived than ovary
inactive workers. These findings show that workers experience costs of
reproduction and suggest that intrinsically high-quality individuals can overcome
these costs. They also raise the possibility that eusocial insect queens exhibit
condition-dependent longevity and hence call into question whether eusociality
entails a truly reversed fecundity-longevity trade-off involving a fundamental
remodelling of conserved genetic and endocrine networks underpinning ageing.
PMID- 28701555
TI - Consistent cooperation in a cichlid fish is caused by maternal and developmental
effects rather than heritable genetic variation.
AB - Studies on the evolution of cooperative behaviour are typically confined to
understanding its adaptive value. It is equally essential, however, to understand
its potential to evolve, requiring knowledge about the phenotypic consistency and
genetic basis of cooperative behaviour. While previous observational studies
reported considerably high heritabilities of helping behaviour in cooperatively
breeding vertebrates, experimental studies disentangling the relevant genetic and
non-genetic components of cooperative behaviour are lacking. In a half-sibling
breeding experiment, we investigated the repeatability and heritability of three
major helping behaviours performed by subordinates of the cooperatively breeding
fish Neolamprologus pulcher To experimentally manipulate the amount of help
needed in a territory, we raised the fish in two environments differing in egg
predation risk. All three helping behaviours were significantly repeatable, but
had very low heritabilities. The high within-individual consistencies were
predominantly due to maternal and permanent environment effects. The perceived
egg predation risk had no effect on helping, but social interactions
significantly influenced helping propensities. Our results reveal that
developmentally plastic adjustments of provided help to social context shape
cooperative phenotypes, whereas heritable genetic variation plays a minor role.
PMID- 28701556
TI - Non-goal-directed recall of specific events in apes after long delays.
AB - We examined if apes spontaneously remember one-time, distinctive events across
long delays when probed by discriminant cues. Apes witnessed an experimenter hide
a cache of food, which they could then retrieve. They retrieved one of two food
types; one more distinctive than the other. Two, 10 or 50 weeks later, the apes
returned to the same enclosure and found a piece of the previously hidden food on
the ground. An experimenter who had not hidden the food was also present. Apes
immediately searched the location where the food was previously hidden (no food
was here), showing recall of the event. One week later, apes returned to the same
enclosure, with the same food on the ground, but now the experimenter that had
hidden the food was present. Again, apes immediately searched the hiding
location. Apes that had not witnessed the hiding event did not search. There was
no significant effect of food type, and retention declined from exposure to the
two-week delay, then levelled, consistent with the forgetting curve in humans
(Ebbinghaus, H. 1964 Memory: a contribution to experimental psychology (transl.
H.A. Ruger & C.E. Bussenvis). New York, NY: Dover. (Original work published
1885.)). This is the first study to show apes can recall a one-time, non-goal
directed event longer than two weeks ago and that apes' recall declines in
accordance with a standard retention function.
PMID- 28701557
TI - The physical boundaries of public goods cooperation between surface-attached
bacterial cells.
AB - Bacteria secrete a variety of compounds important for nutrient scavenging,
competition mediation and infection establishment. While there is a general
consensus that secreted compounds can be shared and therefore have social
consequences for the bacterial collective, we know little about the physical
limits of such bacterial social interactions. Here, we address this issue by
studying the sharing of iron-scavenging siderophores between surface-attached
microcolonies of the bacterium Pseudomonas aeruginosa Using single-cell
fluorescence microscopy, we show that siderophores, secreted by producers,
quickly reach non-producers within a range of 100 um, and significantly boost
their fitness. Producers in turn respond to variation in sharing efficiency by
adjusting their pyoverdine investment levels. These social effects wane with
larger cell-to-cell distances and on hard surfaces. Thus, our findings reveal the
boundaries of compound sharing, and show that sharing is particularly relevant
between nearby yet physically separated bacteria on soft surfaces, matching
realistic natural conditions such as those encountered in soft tissue infections.
PMID- 28701558
TI - Modulation frequency as a cue for auditory speed perception.
AB - Unlike vision, the mechanisms underlying auditory motion perception are poorly
understood. Here we describe an auditory motion illusion revealing a novel cue to
auditory speed perception: the temporal frequency of amplitude modulation (AM
frequency), typical for rattling sounds. Naturally, corrugated objects sliding
across each other generate rattling sounds whose AM-frequency tends to directly
correlate with speed. We found that AM-frequency modulates auditory speed
perception in a highly systematic fashion: moving sounds with higher AM-frequency
are perceived as moving faster than sounds with lower AM-frequency. Even more
interestingly, sounds with higher AM-frequency also induce stronger motion
aftereffects. This reveals the existence of specialized neural mechanisms for
auditory motion perception, which are sensitive to AM-frequency. Thus, in spatial
hearing, the brain successfully capitalizes on the AM-frequency of rattling
sounds to estimate the speed of moving objects. This tightly parallels previous
findings in motion vision, where spatio-temporal frequency of moving displays
systematically affects both speed perception and the magnitude of the motion
aftereffects. Such an analogy with vision suggests that motion detection may rely
on canonical computations, with similar neural mechanisms shared across the
different modalities.
PMID- 28701559
TI - Optimal background matching camouflage.
AB - Background matching is the most familiar and widespread camouflage strategy:
avoiding detection by having a similar colour and pattern to the background.
Optimizing background matching is straightforward in a homogeneous environment,
or when the habitat has very distinct sub-types and there is divergent selection
leading to polymorphism. However, most backgrounds have continuous variation in
colour and texture, so what is the best solution? Not all samples of the
background are likely to be equally inconspicuous, and laboratory experiments on
birds and humans support this view. Theory suggests that the most probable
background sample (in the statistical sense), at the size of the prey, would, on
average, be the most cryptic. We present an analysis, based on realistic
assumptions about low-level vision, that estimates the distribution of background
colours and visual textures, and predicts the best camouflage. We present data
from a field experiment that tests and supports our predictions, using artificial
moth-like targets under bird predation. Additionally, we present analogous data
for humans, under tightly controlled viewing conditions, searching for targets on
a computer screen. These data show that, in the absence of predator learning, the
best single camouflage pattern for heterogeneous backgrounds is the most probable
sample.
PMID- 28701560
TI - Specificity in diversity: single origin of a widespread ciliate-bacteria
symbiosis.
AB - Symbioses between eukaryotes and sulfur-oxidizing (thiotrophic) bacteria have
convergently evolved multiple times. Although well described in at least eight
classes of metazoan animals, almost nothing is known about the evolution of
thiotrophic symbioses in microbial eukaryotes (protists). In this study, we
characterized the symbioses between mouthless marine ciliates of the genus
Kentrophoros, and their thiotrophic bacteria, using comparative sequence analysis
and fluorescence in situ hybridization. Ciliate small-subunit rRNA sequences were
obtained from 17 morphospecies collected in the Mediterranean and Caribbean, and
symbiont sequences from 13 of these morphospecies. We discovered a new
Kentrophoros morphotype where the symbiont-bearing surface is folded into pouch
like compartments, illustrating the variability of the basic body plan.
Phylogenetic analyses revealed that all investigated Kentrophoros belonged to a
single clade, despite the remarkable morphological diversity of these hosts. The
symbionts were also monophyletic and belonged to a new clade within the
Gammaproteobacteria, with no known cultured representatives. Each host
morphospecies had a distinct symbiont phylotype, and statistical analyses
revealed significant support for host-symbiont codiversification. Given that
these symbioses were collected from two widely separated oceans, our results
indicate that symbiotic associations in unicellular hosts can be highly specific
and stable over long periods of evolutionary time.
PMID- 28701561
TI - Common species link global ecosystems to climate change: dynamical evidence in
the planktonic fossil record.
AB - Common species shape the world around us, and changes in their commonness signify
large-scale shifts in ecosystem structure and function. However, our
understanding of long-term ecosystem response to environmental forcing in the
deep past is centred on species richness, neglecting the disproportional impact
of common species. Here, we use common and widespread species of planktonic
foraminifera in deep-sea sediments to track changes in observed global occupancy
(proportion of sampled sites at which a species is present and observed) through
the turbulent climatic history of the last 65 Myr. Our approach is sensitive to
relative changes in global abundance of the species set and robust to factors
that bias richness estimators. Using three independent methods for detecting
causality, we show that the observed global occupancy of planktonic foraminifera
has been dynamically coupled to past oceanographic changes captured in deep-ocean
temperature reconstructions. The causal inference does not imply a direct
mechanism, but is consistent with an indirect, time-delayed causal linkage. Given
the strong quantitative evidence that a dynamical coupling exists, we hypothesize
that mixotrophy (symbiont hosting) may be an ecological factor linking the global
abundance of planktonic foraminifera to long-term climate changes via the
relative extent of oligotrophic oceans.
PMID- 28701562
TI - Nutritional state reveals complex consequences of risk in a wild predator-prey
community.
AB - Animal populations are regulated by the combined effects of top-down, bottom-up
and abiotic processes. Ecologists have struggled to isolate these mechanisms
because their effects on prey behaviour, nutrition, security and fitness are
often interrelated. We monitored how forage, non-consumptive effects (NCEs),
consumptive predation and climatic conditions influenced the demography and
nutritional state of a wild prey population during predator recolonization.
Combined measures of nutrition, survival and population growth reveal that
predators imposed strong effects on the prey population through interacting non
consumptive and consumptive effects, and forage mechanisms. Predation was
directly responsible for adult survival, while declining recruitment was
attributed to predation risk-sensitive foraging, manifested in poor female
nutrition and juvenile recruitment. Substituting nutritional state into the
recruitment model through a shared term reveals that predation risk-sensitive
foraging was nearly twice as influential as summer forage conditions. Our
findings provide a novel, mechanistic insight into the complex means by which
predators and forage conditions affect prey populations, and point to a need for
more ecological studies that integrate behaviour, nutrition and demography. This
line of inquiry can provide further insight into how NCEs interactively
contribute to the dynamics of terrestrial prey populations; particularly, how
predation risk-sensitive foraging has the potential to stabilize predator-prey
coexistence.
PMID- 28701563
TI - Experimental evidence of human recreational disturbance effects on bird-territory
establishment.
AB - The worldwide increase in human outdoor activities raises concerns for wildlife.
Human disturbances, even at low levels, are likely to impact species during
sensitive periods of the annual cycle. However, experimental studies during the
putative sensitive period of territory establishment of birds which not only
investigate low disturbance levels, but which also exclude the effect of habitat
modification (e.g. walking trails) are lacking. Here, we experimentally disturbed
birds in forest plots by walking through twice a day during territory
establishment. Later we compared the breeding bird community of experimentally
disturbed plots with that of undisturbed control plots. We discovered that the
number of territories (-15.0%) and species richness (-15.2%) in disturbed plots
were substantially reduced compared with control plots. Species most affected
included those sensitive to human presence (assessed by flight-initiation
distances), open-cup nesters and above-ground foragers. Long-distance migrants,
however, were unaffected due to their arrival after experimental disturbance took
place. These findings highlight how territory establishment is a sensitive period
for birds, when even low levels of human recreation may be perceived as
threatening, and alter settlement decisions. This can have important implications
for the conservation of species, which might go unnoticed when focusing only on
already established birds.
PMID- 28701564
TI - Spatial storage effect promotes biodiversity during adaptive radiation.
AB - Many ecological communities are enormously diverse. Variation in environmental
conditions over time and space provides opportunities for temporal and spatial
storage effects to operate, potentially promoting species coexistence and
biodiversity. While several studies have provided empirical evidence supporting
the significance of the temporal storage effect for coexistence, empirical tests
of the role of the spatial storage effect are rare. In particular, we know little
about how the spatial storage effect contributes to biodiversity over
evolutionary timescales. Here, we report the first experimental study on the role
of the spatial storage effect in the maintenance of biodiversity in evolving
metacommunities, using the bacterium Pseudomonas fluorescens SBW25 as a
laboratory model of adaptive radiation. We found that intercommunity spatial
heterogeneity promoted phenotypic diversity of P. fluorescens in the presence of
dispersal among local communities, by allowing the spatial storage effect to
operate. Mechanistically, greater niche differences among P. fluorescens
phenotypes arose in metacommunities with intercommunity spatial heterogeneity,
facilitating negative frequency-dependent selection, and thus, the coexistence
among P. fluorescens phenotypes. These results highlight the importance of the
spatial storage effect for biodiversity over evolutionary timescales.
PMID- 28701565
TI - A cosmopolitan late Ediacaran biotic assemblage: new fossils from Nevada and
Namibia support a global biostratigraphic link.
AB - Owing to the lack of temporally well-constrained Ediacaran fossil localities
containing overlapping biotic assemblages, it has remained uncertain if the
latest Ediacaran (ca 550-541 Ma) assemblages reflect systematic biological
turnover or environmental, taphonomic or biogeographic biases. Here, we report
new latest Ediacaran fossil discoveries from the lower member of the Wood Canyon
Formation in Nye County, Nevada, including the first figured reports of
erniettomorphs, Gaojiashania, Conotubus and other problematic fossils. The
fossils are spectacularly preserved in three taphonomic windows and occur in
greater than 11 stratigraphic horizons, all of which are below the first
appearance of Treptichnus pedum and the nadir of a large negative delta13C
excursion that is a chemostratigraphic marker of the Ediacaran-Cambrian boundary.
The co-occurrence of morphologically diverse tubular fossils and erniettomorphs
in Nevada provides a biostratigraphic link among latest Ediacaran fossil
localities globally. Integrated with a new report of Gaojiashania from Namibia,
previous fossil reports and existing age constraints, these finds demonstrate a
distinctive late Ediacaran fossil assemblage comprising at least two groups of
macroscopic organisms with dissimilar body plans that ecologically and temporally
overlapped for at least 6 Myr at the close of the Ediacaran Period. This
cosmopolitan biotic assemblage disappeared from the fossil record at the end of
the Ediacaran Period, prior to the Cambrian radiation.
PMID- 28701567
TI - Correction to 'Population differences in olfaction accompany host shift in
Drosophila mojavensis'.
PMID- 28701566
TI - Chronotype variation drives night-time sentinel-like behaviour in hunter
gatherers.
AB - Sleep is essential for survival, yet it also represents a time of extreme
vulnerability to predation, hostile conspecifics and environmental dangers. To
reduce the risks of sleeping, the sentinel hypothesis proposes that group-living
animals share the task of vigilance during sleep, with some individuals sleeping
while others are awake. To investigate sentinel-like behaviour in sleeping
humans, we investigated activity patterns at night among Hadza hunter-gatherers
of Tanzania. Using actigraphy, we discovered that all subjects were
simultaneously scored as asleep for only 18 min in total over 20 days of
observation, with a median of eight individuals awake throughout the night-time
period; thus, one or more individuals was awake (or in light stages of sleep)
during 99.8% of sampled epochs between when the first person went to sleep and
the last person awoke. We show that this asynchrony in activity levels is
produced by chronotype variation, and that chronotype covaries with age. Thus,
asynchronous periods of wakefulness provide an opportunity for vigilance when
sleeping in groups. We propose that throughout human evolution, sleeping groups
composed of mixed age classes provided a form of vigilance. Chronotype variation
and human sleep architecture (including nocturnal awakenings) in modern
populations may therefore represent a legacy of natural selection acting in the
past to reduce the dangers of sleep.
PMID- 28701568
TI - Feasibility and Efficacy of Microwave Ablation Combined with Iodine-125 Seed
Implantation in Local Control of Recurrent Retroperitoneal Liposarcomas: Initial
Clinical Experience.
AB - INTRODUCTION: The objective of the present study was to evaluate the feasibility,
safety, and short-term efficacy of microwave ablation (MWA) combined with iodine
125 (125I) seed implantation in recurrent retroperitoneal liposarcomas (rRPLs).
MATERIALS AND METHODS: From September 2012 to March 2015, 11 patients were
enrolled in this prospective study. Eleven tumors (median, 9 cm; range, 5.5-12.5
cm) were treated with computerized tomography-guided MWA for 11 sessions and 125I
seed implantation for 18 sessions. 125I seed implantation was performed 4 weeks
after MWA. RESULTS: There were no procedure-related deaths. Post-MWA pain (grade
>=2) was the most common complication (6 of 11 patients, 54.5%), and fever (grade
>=2) was observed in two patients. Reversible nerve injury, defined as transient
limb paresthesia or leg weakness, was observed in one patient. There were fewer
complications associated with the 125I seed implantation procedure compared with
the MWA procedure. All 11 patients who underwent the MWA procedure achieved a
partial response (PR), according to the modified Response Evaluation Criteria in
Solid Tumors, 1 month post-ablation; after 125I seed implantation was performed,
a complete response was observed in three, five, and six target tumors in 3, 6,
and 12 months, respectively. CONCLUSION: In selected patients with rRPLs, MWA
combined with 125I seed implantation is feasible and safe with favorable local
control efficacy. IMPLICATIONS FOR PRACTICE: This study evaluated the
feasibility, safety, and short-term efficacy of microwave ablation (MWA) combined
with iodine-125 (125I) seed implantation in recurrent retroperitoneal
liposarcomas (rRPLs). Results suggest that a single session of MWA may be not
sufficient in large-volume rRPLs and that as a supplement treatment, 125I seed
implantation is safe and easy accessible. MWA combined with 125I seed has
excellent local control effectiveness, and long-term efficacy and survival
benefit still need to be more comprehensively evaluated.
PMID- 28701569
TI - Distinct Tertiary Lymphoid Structure Associations and Their Prognostic Relevance
in HER2 Positive and Negative Breast Cancers.
AB - BACKGROUND: The presence of tumor infiltrating lymphocytes (TIL) is associated
with favorable prognosis. Recent evidence suggested that not only their density,
but also the spatial organization as tertiary lymphoid structures (TLS), play a
key role in determining patient survival. MATERIALS AND METHODS: In a cohort of
248 breast cancers, the clinicopathologic association and prognostic role of TLS
was examined. RESULTS: Tertiary lymphoid structures were associated with higher
tumor grade, apocrine phenotype, necrosis, extensive in situ component,
lymphovascular invasion (LVI), and high TIL. For biomarkers, TLS were associated
with hormone receptors negativity, HER2 positivity, and c-kit expression.
Tertiary lymphoid structures were significantly related to better disease-free
survival (DFS) in HER2 positive (HER2+) breast cancers (log-rank = 4.054), which
was not dependent on high TIL status. The combined TLS and TIL status was an
independent favorable factor associated with DFS in those cases. Interestingly,
tumor cell infiltration into the TLS was found in 41.9% of TLS positive cases. It
was associated with LVI in HER2 negative (HER2-) TLS positive (particularly
estrogen receptor positive [ER+] HER2-) cases. In the ER+ HER2- cases, tumor cell
infiltration into TLS was also associated with increased pathologic nodal stage
(pN) stage and nodal involvement. CONCLUSION: Tertiary lymphoid structures showed
a similar relationship with clinicopathologic features and biomarkers as TIL. The
presence of TLS, irrespective of TIL level, could be an important favorable
prognostic indicator in HER2+ breast cancer patients. Given the significance of
TLS in promoting effective antitumor immunity, further understanding of its
organization and induction may provide new opportunities to improve the current
immunotherapy strategies. IMPLICATIONS FOR PRACTICE: Despite recent interest on
the clinical value of tumor infiltrating lymphocyte (TIL), little was known on
the clinical significance on their spatial organization as tertiary lymphoid
structures (TLS). Although TLS showed similar relationships with
clinicopathologic features and biomarkers as TIL, the prognostic value of TLS,
particularly in HER2 positive cancers, was independent of TIL. Moreover, tumor
infiltration could be present in TLS which appears to be related to tumor
invasion in HER2 negative cancers. Overall, the results demonstrated the
additional value for TLS in HER2 cancer subtypes. Further investigations and its
standardized evaluation will enhance its use as standard practice.
PMID- 28701570
TI - Adipose-Derived Fatty Acid-Binding Proteins Plasma Concentrations Are Increased
in Breast Cancer Patients.
AB - BACKGROUND: Adipose tissue is an endocrine organ that could play a role in tumor
progression via its secreted adipokines. The role of adipose-derived fatty acid
binding protein (FABP) 4 and FABP5 in breast cancer is presently under study, but
their circulating levels in this pathology are poorly known. We analyzed the
blood concentrations of FABP4 and FABP5 in breast cancer patients to determine
whether there is an association between them and breast cancer. MATERIALS AND
METHODS: We studied 294 women in the oncology department with a family history of
breast cancer; 198 of the women had breast cancer, and 96 were healthy controls.
The levels of FABP4, FABP5, lipid profile, standard biochemical parameter, and
high-sensitivity C-reactive protein (hsCRP) were determined. We analyzed the
association of FABP4 and FABP5 with breast cancer, while adjusting for
demographic, anthropometric, and biochemical parameters. RESULTS: Breast cancer
patients had a 24.8% (p < .0001) and 11.4% (p < .05) higher blood concentration
of FABP4 and FABP5, respectively. Fatty acid-binding protein 4 was positively
associated with age, body mass index (BMI), FABP5, very-low-density lipoprotein
cholesterol (VLDLc), non-high-density lipoprote in cholesterol (non-HDLc),
Apolipoprotein B 100 (ApoB100), triglycerides, glycerol, glucose, and hsCRP (p <
.05), and was negatively associated with HDLc (p < .005) in breast cancer
patients. Fatty acid-binding protein 5 was positively associated with BMI, FABP4,
VLDLc, triglycerides, glycerol, and hsCRP (p < .05), and was negatively
associated with HDLc and Apolipoprotein AI (ApoAI) (p < .05) in breast cancer
patients. Using a logistic regression analysis and adjusting for age, BMI, hsCRP,
non-HDLc, and triglycerides, FABP4 was independently associated with breast
cancer (odds ratio [OR]: 1.091 [95% CI: 1.037-1.149]). Moreover, total
cholesterol, VLDLc, non-HDLc, ApoB100, triglycerides, and hsCRP were
significantly increased in breast cancer patients (p < .005). In contrast, the
non-esterified fatty acids concentrations were significantly decreased in breast
cancer patients (p < .05). CONCLUSION: Circulating FABP4 and FABP5 levels were
increased in breast cancer patients compared with controls. The positive
association of FABP4 with breast cancer was maintained after adjusting for
important covariates, while the association with FABP5 was lost. Our data
reinforce the role of adipose tissue and their adipokines in breast cancer.
Despite these data, further studies must be performed to better explain the
prognosis or diagnostic value of these blood parameters and their possible role
in breast cancer. IMPLICATIONS FOR PRACTICE: We focus on the effect of adipose
tissue on cancer, which is increasingly recognized. The association between
adipocyte-derived adipokines and breast cancer opens new diagnosis and therapy
perspectives. In this study, we provide original data concerning FABP4 and FABP5
plasma concentrations in breast cancer patients. Compared to control group,
breast cancer patients show higher FABP4 and FABP5 blood levels. Our data suggest
that, particularly, circulating FABP4 levels could be considered a new
independent breast cancer biomarker. Our work translates basic science data to
clinic linking the relationship between adipose tissue and lipid metabolism to
breast cancer.
PMID- 28701571
TI - Neoadjuvant Therapy with Weekly Nanoparticle Albumin-Bound Paclitaxel for Luminal
Early Breast Cancer Patients: Results from the NABRAX Study (GEICAM/2011-02), a
Multicenter, Non-Randomized, Phase II Trial, with a Companion Biomarker Analysis.
AB - BACKGROUND: Nanoparticle albumin-bound paclitaxel (nab-Paclitaxel) is an
alternative to standard taxanes for breast cancer (BC) treatment. We evaluated
nab-Paclitaxel efficacy as neoadjuvant treatment for early estrogen receptor
positive (ER+), human epidermal growth factor receptor 2-negative (HER2-)
disease. MATERIALS AND METHODS: Women with ER+, HER2-, stage II-III BC were
treated preoperatively with four cycles of weekly nab-Paclitaxel (150 mg/m2), 3
weeks on and 1 week off. We hypothesized that poor pathological response rate
(residual cancer burden [RCB] III; Symmans criteria) would be <=16%. RESULTS:
Eighty-one patients with a median age of 47 years were treated; 64.2% were
premenopausal, and 69% of tumors were stage II. Residual cancer burden III rate
was 28.4% (95% confidence interval [CI]: 18.6%-38.2%), RCB 0+I (good response)
rate was 24.7% (95% CI: 15.3%-34.1%) and RCB 0 (complete response) rate was 7.4%
(95% CI: 1.7%-13.1%). Objective response rate by magnetic resonance imaging was
76.5% and rate of conversion to breast conserving surgery was 40.0%. The most
frequent grade 3 and 4 toxicity was neutropenia (12.3% and 3.7% of patients,
respectively), without any febrile neutropenia. Sensory neuropathy grade 2 and 3
were seen in 25.9% and 2.5% of patients, respectively. Tumor secreted protein,
acidic, cysteine-rich (SPARC) overexpression was significantly associated with
RCB 0 (odds ratio: 0.079; 95% CI: 0.009-0.689; p = .0216). CONCLUSION: Despite
failing to confirm an RCB III rate <=16% in nab-Paclitaxel-treated patients, the
RCB 0+I rate indicates a significant drug antitumor activity with low rates of
grade 3-4 toxicity. Our exploratory biomarker analysis suggests a potential
predictive role of complete response for SPARC. Confirmatory analyses are
warranted, adapting dose and schedule to decrease peripheral neurotoxicity.
(Trial registration: European Clinical Trials Database study number: 2011-004476
10; ClinicalTrials.gov: NCT01565499). IMPLICATIONS FOR PRACTICE: The pathological
response rate (residual cancer burden [RCB]; Symmans criteria) of nanoparticle
albumin-bound paclitaxel administered as neoadjuvant treatment for early estrogen
receptor-positive, human epidermal growth factor receptor 2-negative disease was
evaluated. Whereas poor response (RCB III) was 24.7%, similar to that for
docetaxel, good response (RCB 0+I) reached 23.0%, far superior to the 13% for
docetaxel, while keeping toxicity low. Exploratory biomarker analysis suggests
secreted protein, acidic, cysteine-rich overexpression in tumor cells as a
potential predictor of complete response (RCB 0). Findings point to an
encouraging single-agent neoadjuvant treatment with low toxicity, which warrants
future research and development.
PMID- 28701572
TI - Clinical Application of Targeted Deep Sequencing in Solid-Cancer Patients and
Utility for Biomarker-Selected Clinical Trials.
AB - : Molecular profiling of actionable mutations in refractory cancer patients has
the potential to enable "precision medicine," wherein individualized therapies
are guided based on genomic profiling. The molecular-screening program was
intended to route participants to different candidate drugs in trials based on
clinical-sequencing reports. In this screening program, we used a custom target
enrichment panel consisting of cancer-related genes to interrogate single
nucleotide variants, insertions and deletions, copy number variants, and a subset
of gene fusions. From August 2014 through April 2015, 654 patients consented to
participate in the program at Samsung Medical Center. Of these patients, 588
passed the quality control process for the 381-gene cancer-panel test, and 418
patients were included in the final analysis as being eligible for any anticancer
treatment (127 gastric cancer, 122 colorectal cancer, 62 pancreatic/biliary tract
cancer, 67 sarcoma/other cancer, and 40 genitourinary cancer patients). Of the
418 patients, 55 (12%) harbored a biomarker that guided them to a biomarker
selected clinical trial, and 184 (44%) patients harbored at least one genomic
alteration that was potentially targetable. This study demonstrated that the
panel-based sequencing program resulted in an increased rate of trial enrollment
of metastatic cancer patients into biomarker-selected clinical trials. Given the
expanding list of biomarker-selected trials, the guidance percentage to matched
trials is anticipated to increase. IMPLICATIONS FOR PRACTICE: This study
demonstrated that the panel-based sequencing program resulted in an increased
rate of trial enrollment of metastatic cancer patients into biomarker-selected
clinical trials. Given the expanding list of biomarker-selected trials, the
guidance percentage to matched trials is anticipated to increase.
PMID- 28701573
TI - Quality Assessment of Reporting Performance for EGFR Molecular Diagnosis in Non
Small Cell Lung Cancer.
AB - BACKGROUND: Reports serve as a bridge between laboratories and clinicians, help
synthesize an overwhelming amount of raw data into evidence-based medicine, and
play a significant role in designing clinical treatments. In an effort to
guarantee high-quality epidermal growth factor receptor (EGFR) gene mutation
testing and reporting performance, the National Center for Clinical Laboratories
launched a proficiency testing (PT) scheme reflecting clinical practices in China
since 2014. This study focuses on the quality assessment of gene mutation
reports. MATERIALS AND METHODS: Fifty-three laboratories that submitted reports
in both 2014 and 2016 EGFR gene mutation PT schemes were selected for report
analysis and comparison according to predefined evaluation criteria. RESULTS: The
average score for reports from 2014 was 14 out of 30 points. The overall scores
for reports from 2016 improved substantially, yielding an average score of 20 out
of 30 points. Among the evaluation criteria, general items were well documented
in the reports. However, items specific to molecular diagnosis were far from
satisfactory, and some items were even missing. CONCLUSION: The quality
assessment of clinical written reports from 2014 and 2016 demonstrates that
substantial improvements have been made in overall reporting performance.
However, not all statements pertaining to important elements met expectations. To
continue education, repeated PT schemes need to be executed in a timely fashion
to expose and address existing shortcomings in clinical reports. There remains
ample room for improvement towards generating concise, comprehensive, and
readable reports. IMPLICATIONS FOR PRACTICE: This article compares the quality of
clinical gene mutation reports submitted in 2014 to those submitted in 2016
epidermal growth factor receptor proficiency testing schemes, exposes the
existing shortcomings, and discusses ways to communicate results more effectively
in the future. The findings demonstrate that notable progress was observed in the
overall reporting performance. However, key points specific to molecular
diagnosis were far from expectation, and some items were even missing.
Standardization needs to be emphasized to improve the report format and content.
This article provides a reference that laboratories can use to write concise,
comprehensive, and readily accessible clinical reports.
PMID- 28701574
TI - Antiplatelet Regimen for Patients With Breakthrough Strokes While on Aspirin: A
Systematic Review and Meta-Analysis.
AB - BACKGROUND AND PURPOSE: Optimal antiplatelet therapy after an ischemic stroke or
transient ischemic attack while on aspirin is uncertain. We, therefore, conducted
a systematic review and meta-analysis. METHODS: We searched PubMed (1966 to
August 2016) and bibliographies of relevant published original studies to
identify randomized trials and cohort studies reporting patients who were on
aspirin at the time of an index ischemic stroke or transient ischemic attack and
reported hazard ratio for major adverse cardiovascular events or recurrent stroke
associated with a switch to or addition of another antiplatelet agent versus
maintaining aspirin monotherapy. Estimates were combined using a random effects
model. RESULTS: Five studies with 8723 patients with ischemic stroke or transient
ischemic attack were identified. Clopidogrel was used in 4 cohorts, and
ticagrelor was used in 1 cohort. Pooling results showed that addition of or a
switch to another antiplatelet agent, versus aspirin monotherapy, was associated
with reduced risks of major adverse cardiovascular events (hazard ratio, 0.68;
95% confidence interval, 0.54-0.85) and recurrent stroke (hazard ratio, 0.70; 95%
confidence interval, 0.54-0.92). Each of the strategies of addition of and
switching another antiplatelet agent showed benefit versus continued aspirin
monotherapy, and studies with regimen initiation in the first days after index
event showed more homogenous evidence of benefit. CONCLUSIONS: Among patients who
experience an ischemic stroke or transient ischemic attack while on aspirin
monotherapy, the addition of or a switch to another antiplatelet agent,
especially in the first days after index event, is associated with fewer future
vascular events, including stroke.
PMID- 28701575
TI - Letter by Tampaki et al Regarding Article, "Empagliflozin and Cerebrovascular
Events in Patients With Type 2 Diabetes Mellitus at High Cardiovascular Risk".
PMID- 28701576
TI - Estimated Impact of Emergency Medical Service Triage of Stroke Patients on
Comprehensive Stroke Centers: An Urban Population-Based Study.
AB - BACKGROUND AND PURPOSE: The American Stroke Association recommends that Emergency
Medical Service bypass acute stroke-ready hospital (ASRH)/primary stroke center
(PSC) for comprehensive stroke centers (CSCs) when transporting appropriate
stroke patients, if the additional travel time is <=15 minutes. However, data on
additional transport time and the effect on hospital census remain unknown.
METHODS: Stroke patients >=20 years old who were transported from home to an
ASRH/PSC or CSC via Emergency Medical Service in 2010 were identified in the
Greater Cincinnati area population of 1.3 million. Addresses of all patients'
residences and hospitals were geocoded, and estimated travel times were
calculated. We estimated the mean differences between the travel time for
patients taken to an ASRH/PSC and the theoretical time had they been transported
directly to the region's CSC. RESULTS: Of 929 patients with geocoded addresses,
806 were transported via Emergency Medical Service directly to an ASRH/PSC. Mean
additional travel time of direct transport to the CSC, compared with transport to
an ASRH/PSC, was 7.9+/-6.8 minutes; 85% would have <=15 minutes added transport
time. Triage of all stroke patients to the CSC would have added 727 patients to
the CSC's census in 2010. Limiting triage to the CSC to patients with National
Institutes of Health Stroke Scale score of >=10 within 6 hours of onset would
have added 116 patients (2.2 per week) to the CSC's annual census. CONCLUSIONS:
Emergency Medical Service triage to CSCs based on stroke severity and symptom
duration may be feasible. The impact on stroke systems of care and patient
outcomes remains to be determined and requires prospective evaluation.
PMID- 28701577
TI - Response by Zinman et al to Letter Regarding Article, "Empagliflozin and
Cerebrovascular Events in Patients With Type 2 Diabetes Mellitus at High
Cardiovascular Risk".
PMID- 28701578
TI - Circular RNA Expression Profiles Alter Significantly in Mouse Brain After
Transient Focal Ischemia.
AB - BACKGROUND AND PURPOSE: Circular RNAs (circRNAs) are a novel class of noncoding
RNAs formed from many protein-coding genes by backsplicing. Although their
physiological functions are not yet completely defined, they are thought to
control transcription, translation, and microRNA levels. We investigated whether
stroke changes the circRNAs expression profile in the mouse brain. METHODS: Male
C57BL/6J mice were subjected to transient middle cerebral artery occlusion, and
circRNA expression profile was evaluated in the penumbral cortex at 6, 12, and 24
hours of reperfusion using circRNA microarrays and real-time PCR. Bioinformatics
analysis was conducted to identify microRNA binding sites, transcription factor
binding, and gene ontology of circRNAs altered after ischemia. RESULTS: One
thousand three-hundred twenty circRNAs were expressed at detectable levels mostly
from exonic (1064) regions of the genes in the cerebral cortex of sham animals.
Of those, 283 were altered (>2-fold) at least at one of the reperfusion time
points, whereas 16 were altered at all 3 time points of reperfusion after
transient middle cerebral artery occlusion compared with sham. Postischemic
changes in circRNAs identified by microarray analysis were confirmed by real-time
PCR. Bioinformatics showed that these 16 circRNAs contain binding sites for many
microRNAs. Promoter analysis showed that the circRNAs altered after stroke might
be controlled by a set of transcription factors. The major biological and
molecular functions controlled by circRNAs altered after transient middle
cerebral artery occlusion are biological regulation, metabolic process, cell
communication, and binding to proteins, ions, and nucleic acids. CONCLUSIONS:
This is a first study that shows that stroke alters the expression of circRNAs
with possible functional implication to poststroke pathophysiology.
PMID- 28701579
TI - Detecting Intracranial Vessel Wall Lesions With 7T-Magnetic Resonance Imaging:
Patients With Posterior Circulation Ischemia Versus Healthy Controls.
AB - BACKGROUND AND PURPOSE: Vessel wall magnetic resonance imaging sequences have
been developed to directly visualize the intracranial vessel wall, enabling
detection of vessel wall changes, including those that have not yet caused
luminal narrowing. In this study, vessel wall lesion burden was assessed in
patients with recent posterior circulation ischemia using 7T-magnetic resonance
imaging and compared with matched healthy controls. METHODS: Fifty subjects (25
patients and 25 matched healthy controls) underwent 7T-magnetic resonance imaging
with an intracranial vessel wall sequence before and after contrast
administration. Two raters scored the presence and contrast enhancement of
arterial wall lesions in individual segments of the circle of Willis and its
primary branches. Total burden and distribution of vessel wall lesions and lesion
characteristics (configuration, thickening pattern, and contrast enhancement)
were compared both between and within both groups. RESULTS: Overall, vessel wall
lesion burden and distribution were comparable between patients and controls.
Regarding individual arterial segments, only vessel wall lesions in the posterior
cerebral artery were more frequently observed in patients (18.0%) than in
controls (5.4%; P=0.003). Many of these lesions showed enhancement, both in
patients (48.9%) and in controls (43.5%; P=0.41). In patients, the proportion of
enhancing lesions was higher in the posterior circulation (53.3%) than in the
anterior circulation (20.6%; P=0.008). CONCLUSIONS: Although overall intracranial
vessel wall lesion burden and contrast enhancement were comparable between
patients with recent posterior circulation ischemia and healthy controls, this
study also revealed significant differences between the 2 groups, suggesting an
association between posterior circulation lesion burden/enhancement and ischemic
events. CLINICAL TRIAL REGISTRATION: URL: http://www.trialregister.nl. Unique
identifier: NTR5688.
PMID- 28701580
TI - Editor's Correspondence.
PMID- 28701581
TI - The Role of the Amygdala in Value-Based Learning.
PMID- 28701582
TI - Protecting Mitochondrial Health: A Unifying Mechanism in Adult Neurogenesis.
PMID- 28701584
TI - A missing voice: the human rights of children to a tobacco-free environment.
AB - In this commentary, we flag the importance of taking a child-rights approach in
the context of tobacco control, which is thus far unprecedented. This text was
written in response to the Seventh Conference of States Parties of WHOs Framework
Convention on Tobacco Control held in India from 7 to 12 November 2016.While the
links between tobacco control and human rights were emphasised at this
conference, a child-rights approach was missing. We argue that this novel angle
provides important legal tools to protect the health and well-being of children.
Because children are seen as 'replacement smokers' by the tobacco industry,
protecting children in this context is key to haltering the devastating effects
of tobacco use and exposure worldwide.
PMID- 28701591
TI - View Point.
PMID- 28701585
TI - Banning tobacco price promotions, smoking-related beliefs and behaviour: findings
from the International Tobacco Control Four Country (ITC 4C) Survey.
AB - BACKGROUND: Ecological models emphasise multilevel influences on health
behaviours. While studies show that exposure to price promotions is associated
with smoking behaviour and its antecedents, less is known about whether these
associations differ by macro-level factors such as national price promotion
policies. METHODS: Current and former smokers (N=4698) from the International
Tobacco Control Policy Evaluation Project four-country cohort were included in
weighted multivariate logistic regression models to examine individual-level
associations between exposure to price promotions at waves 7 and 8 (conducted in
2008-2009 and 2010-2011) and beliefs (social and injunctive norms, functional
value of smoking, misconceptions around smoking and beliefs of tobacco industry
and its regulations) and behaviour at wave 8, stratified by whether countries
allow (Australia and USA) or ban (Canada and UK) price promotions. RESULTS:
Associations between exposure to price promotions and smoking-related beliefs and
behaviour differed by national price promotion policies. In countries that allow
price promotions, participants repeatedly exposed to price promotions at waves 7
and 8 were more likely to associate functional values to smoking (ie, calms down
when stressed (adjusted OR (AOR) 1.83) and to be current smokers at wave 8 (AOR
1.94). In countries that ban price promotions, participants repeatedly exposed to
price promotions were less likely to hold misconceptions around smoking (ie,
harsher smoke is more dangerous). CONCLUSIONS: Differential associations emerged
between exposure to price promotions, smoking-related beliefs and behaviour
across countries with and without a price promotions ban. Adopting price
promotion bans could ameliorate the associations between exposure to price
promotions and smoking beliefs and behaviours.
PMID- 28701592
TI - Risk factors of postcardiotomy ventricular dysfunction in moderate-to-high risk
patients undergoing open-heart surgery.
AB - INTRODUCTION: Ventricular dysfunction requiring inotropic support frequently
occurs after cardiac surgery, and the associated low cardiac output syndrome
largely contributes to postoperative death. We aimed to study the incidence and
potential risk factors of postcardiotomy ventricular dysfunction (PCVD) in
moderate-to-high risk patients scheduled for open-heart surgery. METHODS: Over a
5-year period, we prospectively enrolled 295 consecutive patients undergoing
valve replacement for severe aortic stenosis or coronary artery bypass surgery
who presented with Bernstein-Parsonnet scores >7. The primary outcome was the
occurrence of PCVD as defined by the need for sustained inotropic drug support
and by transesophageal echography. The secondary outcomes included in-hospital
mortality and the incidence of any major adverse events as well as Intensive Care
Unit (ICU) and hospital length of stay. RESULTS: The incidence of PCVD was 28.4%.
Patients with PCVD experienced higher in-hospital mortality (12.6% vs. 0.6% in
patients without PCVD) with a higher incidence of cardiopulmonary and renal
complications as well as a prolonged stay in ICU (median + 2 days). Myocardial
infarct occurred more frequently in patients with PCVD than in those without PCVD
(19 [30.2%] vs. 12 [7.6%]). By logistic regression analysis, we identified four
independent predictors of PCVD: left ventricular ejection fraction <40% (odds
ratio [OR] = 6.36; 95% confidence interval [CI], 2.59-15.60), age older than 75
years (OR = 3.35; 95% CI, 1.64-6.81), prolonged aortic clamping time (OR = 3.72;
95% CI, 1.66-8.36), and perioperative bleeding (OR = 2.33; 95% CI, 1.01-5.41).
The infusion of glucose-insulin-potassium was associated with lower risk of PCVD
(OR = 0.14; 95% CI, 0.06-0.33). CONCLUSIONS: This cohort study indicates that
age, preoperative ventricular function, myocardial ischemic time, and
perioperative bleeding are predictors of PCVD which is associated with poor
clinical outcome.
PMID- 28701593
TI - Neutrophil gelatinase-associated lipocalin as a biomarker for predicting acute
kidney injury during off-pump coronary artery bypass grafting.
AB - BACKGROUND: Acute kidney injury (AKI) following cardiac surgery is a major
complication resulting in increased morbidity, mortality, and economic burden. In
this study, we assessed the usefulness of estimating serum neutrophil gelatinase
associated lipocalin (NGAL) as a biomarker in predicting AKI in patients with
stable chronic kidney disease (CKD) and undergoing off-pump coronary artery
bypass grafting (OP-CABG). PATIENTS AND METHODS: We prospectively studied sixty
nondialysis-dependent CKD patients with estimated glomerular filtration rate <60
ml/min/1.73 m2 who required elective OP-CABG. Patients were randomized into two
groups, Group D received dopamine infusion at 2 MUg/kg/min following anesthesia
induction till the end of the surgery and Group P did not receive any
intervention. Serum creatinine, NGAL, brain natriuretic peptide, and troponin-I
were estimated at specified intervals before, during, and after surgery. The
results of the study patients were also compared to a simultaneous matched cohort
control of thirty patients (Group A) without renal dysfunction who underwent OP
CABG. RESULTS: No patient required renal replacement therapy, and no mortality
was observed during perioperative and hospitalization period. Six patients from
control group (n = 30), ten patients from placebo group (n = 30), and 12 patients
from dopamine group (n = 30) developed stage 1 AKI. However, we did not observe
any stage 2 and stage 3 AKI among all the groups. There was a significant
increase in serum NGAL levels at the end of surgery and 24 h postoperatively in
placebo and dopamine groups as compared to the control. CONCLUSION: The
measurement of NGAL appears to predict the occurrence of AKI after OP-CAB
surgery. However, large multicentric studies may be required to confirm the
findings of this study.
PMID- 28701594
TI - Coronary artery bypass graft patients' perception about the risk factors of
illness: Educational necessities of second prevention.
AB - BACKGROUND: Patients' beliefs about the cause of cardiac disease (perceived risk
factors) as part of the global psychological presentation are influenced by
patients' health knowledge. Hence, the present study aimed to assess the
relationship between actual and perceived risk factors, identification of
underestimated risk factors, and indication of underestimation of every risk
factor. MATERIALS AND METHODS: In this cross-sectional study, data of 313
coronary artery bypass graft (CABG) patients admitted to one hospital in the west
of Iran were collected through a demographic interview, actual risk factors'
checklist, open single item of perceived risk factors, and a life stressful
events scale. Data were analyzed by means of Spearman's correlation coefficients
and one-sample Z-test for proportions. RESULTS: Although there are significant
relations between actual and perceived risk factors related to hypertension,
family history, diabetes, smoking, and substance abuse (P < 0.05), there is no
relation between the actual and perceived risk factors, and patients
underestimate the role of actual risk factors in disease (P < 0.001). The
patients underestimated the role of aging (98.8%), substance abuse (95.2%),
overweight and obesity (94.9%), hyperlipidemia (93.1%), family history (90.3%),
and hypertension (90%) more than diabetes (86.1%), smoking (72.5%), and stress
(54.7%). CONCLUSION: Cardiac patients seem to underestimate the role of aging,
substance abuse, obesity and overweight, hyperlipidemia, family history, and
hypertension more than other actual risk factors. Therefore, these factors should
be highlighted to patients to help them to (i) increase the awareness of actual
risk factors and (ii) promote an appropriate lifestyle after CABG surgery.
PMID- 28701595
TI - Cardiovascular operation: A significant risk factor of arytenoid cartilage
dislocation/subluxation after anesthesia.
AB - BACKGROUND: Arytenoid cartilage dislocation/subluxation is one of the rare
complications following tracheal intubation, and there have been no reports about
risk factors leading this complication. From our clinical experience, we have an
impression that patients undergoing cardiovascular operations tend to be
associated with this complication. AIMS: We designed a large retrospective study
to reveal the incidence and risk factors predicting the occurrence and to examine
whether our impression is true. SETTINGS AND DESIGNS: This was a retrospective
study. METHODS: We retrospectively studied 19,437 adult patients who were
intubated by an anesthesiologist in our operation theater from 2002 to 2008. The
tracheal intubation was performed by a resident anesthesiologist managing the
patients. Only patients whose postoperative voice was disturbed more than 7 days
were referred to the Department of Otorhinolaryngology-Head and Neck Surgery and
examined using laryngostroboscopy by a laryngologist to diagnose arytenoid
cartilage dislocation/subluxation. We evaluated age, sex, weight, height,
duration of intubation, difficult intubation, and major cardiovascular operation
as risk factors to lead this complication. STATISTICAL ANALYSIS: The data were
analyzed by logistic regression analysis to assess factors for arytenoid
cartilage dislocation/subluxation after univariate analyses using logistic
regression analysis. RESULTS: Our analysis indicated that difficult intubation
(odds ratio: 12.1, P = 0.018) and cardiovascular operation (odds ratio: 9.9, P <
0.001) were significant risk factors of arytenoid cartilage
dislocation/subluxation. CONCLUSION: The present study demonstrated that major
cardiovascular operation is one of the significant risk factors leading this
complication.
PMID- 28701596
TI - Propofol versus Ketofol for Sedation of Pediatric Patients Undergoing
Transcatheter Pulmonary Valve Implantation: A Double-blind Randomized Study.
AB - OBJECTIVE: The study was done to compare propofol and ketofol for sedation of
pediatric patients scheduled for elective pulmonary valve implantation in a
catheterization laboratory. DESIGN: This was a double-blind randomized study.
SETTING: This study was conducted in Prince Sultan Cardiac Centre, Saudi Arabia.
PATIENTS AND METHODS: The study included 60 pediatric patients with pulmonary
regurge undergoing pulmonary valve implantation. INTERVENTION: The study included
sixty patients, classified into two groups (n = 30). Group A: Propofol was
administered as a bolus dose (1-2 mg/kg) and then a continuous infusion of 50-100
MUg/kg/min titrated as needed. Group B: Ketofol was administered 1-2 mg/kg and
then infusion of 20-60 MUg/kg/min. The medication was prepared by the nursing
staff and given to anesthetist blindly. MEASUREMENTS: The monitors included heart
rate, mean arterial blood pressure, respiratory rate, temperature, SPO2and PaCO2,
Michigan Sedation Score, fentanyl dose, antiemetic medications, and Aldrete
score. MAIN RESULTS: The comparison of heart rate, mean arterial pressure,
respiratory rate, temperature, SPO2and PaCO2, Michigan Sedation Score, and
Aldrete score were insignificant (P > 0.05). The total fentanyl increased in
Group A more than Group B (P = 0.045). The required antiemetic drugs increased in
Group A patients more than Group B (P = 0.020). The durations of full recovery
and in the postanesthesia care unit were longer in Group A than Group B (P =
0.013, P < 0.001, respectively). CONCLUSION: The use of propofol and ketofol is
safe and effective for sedation of pediatric patients undergoing pulmonary valve
implantation in a catheterization laboratory. However, ketofol has many
advantages more than the propofol. Ketofol has a rapid onset of sedation, a rapid
recovery time, decreased incidence of nausea and vomiting and leads to rapid
discharge of patients from the postanesthesia care unit.
PMID- 28701597
TI - Randomized comparative study of intravenous infusion of three different fixed
doses of milrinone in pediatric patients with pulmonary hypertension undergoing
open heart surgery.
AB - BACKGROUND: Pulmonary hypertension secondary to congenital heart disease is a
common problem in pediatric patients presenting for open heart surgery. Milrinone
has been shown to reduce pulmonary vascular resistance and pulmonary artery
pressure in pediatric patients and neonates postcardiac surgery. We aimed to
evaluate the postoperative outcome in such patients with three different fixed
maintenance doses of milrinone. METHODOLOGY: Patients were randomized into three
groups. All patients received fixed bolus dose of milrinone 50 MUg/kg on pump
during rewarming. Following this, patients in low-dose group received infusion of
milrinone at the rate of 0.375 MUg/kg/min, medium-dose group received 0.5
MUg/kg/min, and high-dose group received 0.75 MUg/kg/min over 24 h. Heart rate,
mean arterial pressure (MAP), mean airway pressure (MaP), oxygenation index (OI),
and central venous pressure (CVP) were compared at baseline and 24 h
postoperatively. Dose of inotropic requirement, duration of ventilatory support
and Intensive Care Unit (ICU) stay were noted. RESULTS: MAP, MaP, OI, and CVP
were comparable in all three groups postoperatively. All patients in the low-dose
group required low inotropic support while 70% of patients in the high-dose group
needed high inotropic support to manage episodes of hypotension (P = 0.000).
Duration of ventilatory support and ICU stay in all three groups was comparable
(P = 0.412, P = 0.165). CONCLUSION: Low-dose infusions while having a clinical
impact were more beneficial in avoiding adverse events and decreasing inotropic
requirement without affecting duration of ventilatory support and duration of ICU
stay.
PMID- 28701598
TI - The blalock and taussig shunt revisited.
AB - The systemic to pulmonary artery shunts are done as palliative procedures for
cyanotic congenital heart diseases ranging from simple tetralogy of Fallots
(TOFs)/pulmonary atresia (PA) to complex univentricular hearts. They allow growth
of pulmonary arteries and maintain regulated blood flow to the lungs till a
proper age and body weight suitable for definitive corrective repair is reached.
We have reviewed the BT shunt with its anaesthtic considerations and management
of associated complications.
PMID- 28701599
TI - Interesting images: Multiple coronary artery aneurysms.
AB - We present the case of a 65-year-old male who presented with stable angina and
dyspnea on exertion. His initial workup yielded a positive treadmill stress test
for reversible apical ischemia, and transthoracic echocardiogram demonstrated
impaired systolic function. Cardiac catheterization was then performed, revealing
severe atherosclerotic disease including multiple coronary artery aneurysms. As a
result, the patient was advised to and subsequently underwent a coronary artery
bypass graft. This case highlights the presence of multiple coronary artery
aneurysms and the ability to appreciate these pathologic findings on multiple
imaging modalities, including coronary angiogram, transesophageal
echocardiography, and direct visualization through the surgical field.
PMID- 28701600
TI - Inadequate venous drainage-transesophageal echocardiography as rescue.
AB - Malposition of venous cannula can cause inadequate venous drainage during
cardiopulmonary bypass. It would be good clinical practice to use TEE to check
the position of inferior venous cannula to avoid this problem at the earliest.
PMID- 28701601
TI - An antenatal diagnosis: Congenital high airway obstruction.
AB - Congenital high airway obstruction (CHAOS) is a rare lethal fetal malformation
characterised by obstruction to the fetal upper airway, which can be partial or
complete. Antenatal diagnosis of CHAOS is important due to recent management
options. Diagnosis is made with secondary changes such as hyperechoic enlarged
lungs resulting in mediastinal compression, ascites, hydrops, flattened or
everted diaphragms and dilated distal airways. We reported a case of CHAOS,
antenatally on ultrasonography (USG) at 20 weeks of gestation.
PMID- 28701602
TI - To evaluate dexmedetomidine as an additive to propofol for sedation for elective
cardioversion in a cardiac intensive care unit: A double-blind randomized
controlled trial.
AB - INTRODUCTION: Propofol may lead to patient recall and discomfort when used for
sedation in elective cardioversion. The aim of the present study was to evaluate
dexmedetomidine as an additive to propofol for sedation in elective
cardioversion. MATERIALS AND METHODS: A total of 500 patients undergoing elective
cardioversion were randomized into Group 1 (n = 250) and Group 2 (n = 250) on the
basis of computer-generated randomization table. Patients in Group 1 were given
dexmedetomidine (1 mcg/kg) over 10 min before giving propofol (1 mg/kg), while
patients in Group 2 were given only propofol (1 mg/kg). One or two additional
doses of 0.5 mg/kg propofol were given if modified Ramsay Sedation Score (mRSS)
was <5. Number of patients requiring additional doses were noted. Any hemodynamic
or respiratory complication along with the mean time to recovery (mRSS = 1) was
recorded. Patient recall, patient discomfort, and further requirement of
cardioversion in the next 24 h were also noted. RESULTS: About 10% patients in
Group 1 and 64% patients in Group 2 required the first additional dose of
propofol. While no patient in Group 1 required second dose, 16% patients in Group
2 required second dose of propofol. The mean time to recovery in Group 1 was 8.36
+/- 3.08 min and 8.22 +/- 2.38 min in Group 2 (P = 0.569). Sixty-seven patients
(26.8%) in Group 1 and 129 patients (51.6%) in Group 2 reported remembering
something (P < 0.0001), i.e., recall. Thirty-five patients (14%) in Group 1 and
79 patients (31.6%) in Group 2 reported dreaming during the procedure (P <
0.0001). Visual analog scale score was higher in Group 1 as compared to Group 2.
Six patients in Group 1 and 24 patients in Group 2 had a requirement of repeat
cardioversion in 24-h follow-up (P = 0.001). CONCLUSIONS: Dexmedetomidine is a
useful adjunct to propofol for elective cardioversion.
PMID- 28701603
TI - Is endothelin gene polymorphism associated with postoperative atrial fibrillation
in patients undergoing coronary artery bypass grafting?
AB - BACKGROUND: The mechanism of development of atrial fibrillation (AF) in patients
undergoing coronary artery bypass grafting (CABG) has not been clearly defined,
and the involvement of multiple factors such as advanced age, withdrawal of beta
blockers, inadequate atrial protection, and electrolyte imbalance, particularly
hypomagnesemia has been documented by several authors. Despite all the available
pharmacologic prophylaxis, incidence of AF still remains high in this group of
patients. This unexplained cause could be genetic inheritance of endothelin-1 (ET
1) gene which is thought to have a pro-arrhythmogenic effect. AIM: This study
aims to investigate the relationship between plasma ET-1 concentrations, ET-1
gene polymorphisms in loci -1370 T/G, -134 (3A/4A) Ins/del, Lys198Asn (G/T), and
occurrence of AF in patients undergoing CABG. METHODOLOGY: Ninety-eight
nonrelated, nondiabetic patients over a period of 4 years undergoing routine CABG
were selected for the present study. All patients were genotyped for three single
nucleotide polymorphisms (SNPs) in loci -1370 T/G, -134 (3A/4A) Ins/del, and
Lys198Asn (G/T) in the ET-1 gene by gene sequencing. The plasma ET-1
concentrations were measured using an ET immunoassay. RESULTS: Plasma ET-1
concentrations were higher in AF+ group (P = 0.001) as compared to AF- group. The
allele frequencies between AF+ and AF- group were significantly different only
with respect to the Lys198Asn (G/T) SNP of the ET-1 gene. CONCLUSION: The study
described the possible correlation of polymorphism of ET gene in CABG population
from India. The ET-1 gene might play a disease-modifying role in atrial
fibrillation.
PMID- 28701604
TI - Major vessel venous thrombosis in patients of posttubercular chronic constrictive
pericarditis undergoing pericardectomy: A rare scenario.
AB - We are reporting two cases of neck and arm major venous thrombosis in patients of
posttubercular chronic constrictive pericarditis posted for pericardectomy. There
was unanticipated difficulty in placement of Internal Jugular vein catheter and
subsequent ultrasound revealed thrombosis in the major veins. It was not
diagnosed in the preoperative period. This report raises this major complication
and highlights the use of ultrasound in such scenarios.
PMID- 28701605
TI - Role of transesophageal echocardiography in surgical retrieval of embolized
amplatzer device and closure of coronary-cameral fistula.
AB - Congenital coronary artery fistula is an uncommon anomaly. Transcatheter coil
embolization or Amplatzer vascular plug device closure of fistula is often done
in symptomatic patients with safe accessibility to the feeding coronary artery.
Embolization of Amplatzer vascular plug device is rare. We report an 11-year-old
male child who presented to us with increasing shortness of breath for 7 years.
He had a history of Amplatzer vascular plug device closure of right coronary
cameral fistula 8 years back. Echocardiography demonstrated a dilated aneurysmal
right coronary artery with turbulent jet entering into the right ventricle (RV)
and device embolized into the left pulmonary artery (LPA). Cardiac
catheterization eventually confirmed the diagnosis. Surgical closure of fistula
and retrieval of device was done using cardiopulmonary bypass. Intraoperatively
transesophageal echocardiogram helped in localizing fistula opening in the RV
below the anterior leaflet of tricuspid valve, continuous monitoring to prevent
further distal embolization of the device during surgical handling, and
assessment of completeness of repair of the fistula and LPA following retrieval
of the device.
PMID- 28701606
TI - Silicone tracheobronchial stent: A rare cause for bronchoesophageal fistula and
distortion of airway anatomy.
AB - Silicone tracheobronchial stents are being increasingly used in a large number of
patients for the treatment of tracheal stenosis. One very rare complication due
to tracheobronchial stenting is bronchoesophageal fistula (BEF), which has been
associated with the use of metallic stents. We report intraoperative management
of a patient undergoing repair of a BEF, following previous insertion of a
silicone Y-stent that is soft in texture and has not been implicated for this
complication till date. In addition, misalignment of this silicone
tracheobronchial Y-stent resulted in a tracheal mucosal bulge proximal to the
stent that vanished after its removal.
PMID- 28701607
TI - Anesthetic challenges of extrinsic trachea-bronchial compression due to posterior
mediastinal mass: Our experience with a large esophageal mucocele.
AB - Large posterior mediastinal masses may lead threatening complications such as
critical tracheobronchial compression. Airway management in these individuals is
a challenge and being a lower airway obstruction; rescue strategies are limited.
We encountered one such case of a large esophageal mucocele causing extrinsic
tracheobronchial compression. We have described the anesthetic management of this
case using awake fiber-optic assessment followed by intubation. Close
communication with the surgical team, meticulous planning of airway management,
and early drainage of the mucocele are the cornerstones of management in such
patients.
PMID- 28701608
TI - Management of a case of double aortic arch with tracheal compression complicated
with postoperative tracheal restenosis.
AB - Tracheal stenosis in association with the double aortic arch (DAA) is uncommon;
however, it carries a high risk of morbidity, mortality, and restenosis. Although
surgery is the mainstay of managing a case of the DAA with tracheal stenosis,
management of tracheal restenosis requires a multidisciplinary approach. In this
case report, we present our successful experience in managing a child of DAA with
tracheal stenosis who developed tracheal restenosis after sliding tracheoplasty
of trachea.
PMID- 28701609
TI - A rare case of acyanotic congenital heart disease, large patent ductus arteriosus
with pre-ductal coarctation of descending thoracic aorta with patent ductus
arteriosus closure and extra anatomical bypass grafting.
AB - We report a case of 18-year-old female patient with large patent ductus
arteriosus (PDA)-preductal coarctation of descending thoracic aorta. She
underwent large PDA closure with a prosthetic graft from ascending aorta to
descending thoracic aorta by mid-sternotomy on cardiopulmonary bypass machine
under total hypothermic circulatory arrest.
PMID- 28701610
TI - Idarucizumab (Praxbind) for reversal of pradaxa prior to emergent repair of
contained ruptured transverse arch aneurysm.
AB - Idarucizumab before cardiopulmonary bypass was used for the reversal of
dabigatran during an emergent frozen elephant trunk repair of a transverse arch
aneurysm. Reversal was successful and minimal not massive transfusion was
required with no abnormal sequelae seen with use before cardiopulmonary bypass.
PMID- 28701611
TI - The utility of targeted perioperative transthoracic echocardiography in managing
an adult patient with anomalous origin of the left coronary artery-pulmonary
artery for noncardiac surgery.
AB - Congenital coronary artery anomalies as a whole are uncommon. Abnormal origin of
the left coronary artery from the pulmonary artery (ALCAPA) is probably the most
common congenital coronary defect. An overwhelming majority of the patients with
untreated ALCAPA do not survive to adulthood. As yet, there is no consensus on
the management of adults with ALCAPA. We describe a patient with breast
malignancy and incidentally detected ALCAPA; primacy was given to treatment of
the oncologic condition as a first step. Anesthesia management was focused on
maintaining adequate collateral coronary perfusion and avoidance of excessive
loading of the left ventricle. This was achieved using a simplified transthoracic
echocardiography (TTE) protocol at the time of induction of anesthesia; TTE was
also used to reconfirm the absence of disturbances in myocardial function at the
end of surgery. We sugggest the routine use of tte in managing perioperative care
in low resource settings when the underlying cardiac disease is rare and the
evidence base if often insufficient.
PMID- 28701612
TI - Sugammadex to reverse neuromuscular blockade in a child with a past history of
cardiac transplantation.
AB - Sugammadex is a novel agent for the reversal of neuromuscular blockade. The speed
and efficacy of reversal with sugammadex are significantly faster than
acetylcholinesterase inhibitors, such as neostigmine. Sugammadex also has a
limited adverse profile when compared with acetylcholinesterase inhibitors,
specifically in regard to the incidence of bradycardia. This adverse effect may
be particularly relevant in the setting of a heart transplant recipient with a
denervated heart. The authors present a case of an 8-year-old child, status
postcardiac transplantation, who required anesthetic care for laparoscopy and
lysis of intra-abdominal adhesions. Sugammadex was used to reverse neuromuscular
blockade and avoid the potential adverse effects of neostigmine. The unique
mechanism of action of sugammadex is discussed, previous reports of its use in
this unique patient population are reviewed, and its potential benefits compared
to traditional acetylcholinesterase inhibitors are presented.
PMID- 28701613
TI - Management of iatrogenic pulmonary artery injury during pulmonary artery banding.
AB - Pulmonary Artery banding (PAB) is limited to selected patients who cannot undergo
primary repair due to complex anatomy, associated co-morbidities, as a part of
staged univentricular palliation, and for preparing the left ventricle prior to
an arterial switch operation. We report a catastrophic iatrogenic complication in
which the pulmonary artery was injured during the PAB. We discuss its multi
pronged management.
PMID- 28701614
TI - Methylene blue for post-cardioplumonary bypass vasoplegic syndrome.
PMID- 28701615
TI - Bentall procedure in a patient with parkinson disease.
PMID- 28701616
TI - Asystole following neuromuscular blockade reversal in cardiac transplant
patients.
PMID- 28701617
TI - Is Off-pump cardiac surgery ready for goal-directed therapy?
PMID- 28701618
TI - Appropriate size of double-lumen tubes in Asians.
PMID- 28701619
TI - Anesthesia challenges in patent ductus arteriosus stenting for congenital heart
disease.
PMID- 28701620
TI - Comparative analysis of the intestinal flora in type 2 diabetes and nondiabetic
mice.
AB - A relationship between type 2 diabetes mellitus (T2DM) and intestinal flora has
been suggested since development of analysis technology for intestinal flora. An
animal model of T2DM is important for investigation of T2DM. Although there are
some animal models of T2DM, a comparison of the intestinal flora of healthy
animals with that of T2DM animals has not yet been reported. The intestinal flora
of Tsumura Suzuki Obese Diabetes (TSOD) mice was compared with that of Tsumura,
Suzuki, Non Obesity (TSNO) mice in the present study. The TSOD mice showed
typical type 2 diabetes symptoms, which were high-fat diet-independent. The TSOD
and the TSNO mouse models were derived from the same strain, ddY. In this study,
we compared the intestinal flora of TSOD mice with that if TSNO mice at 5 and 12
weeks of age. We determined that that the number of operational taxonomic units
(OTUs) was significantly higher in the cecum of TSOD mice than in that of TSNO
mice. The intestinal flora of the cecum and that of the feces were similar
between the TSNO and the TSOD strains. The dominant bacteria in the cecum and
feces were of the phyla Firmicutes and Bacteroidetes. However, the content of
some bacterial species varied between the two strains. The percentage of
Lactobacillus spp. within the general intestinal flora was higher in TSOD mice
than in TSNO mice. In contrast, the percentages of order Bacteroidales and family
Lachnospiraceae were higher in TSNO mice than in TSOD mice. Some species were
observed only in TSOD mice, such as genera Turicibacter and SMB53 (family
Clostridiaceae), the percentage of which were 3.8% and 2.0%, respectively.
Although further analysis of the metabolism of the individual bacteria in the
intestinal flora is essential, genera Turicibacter and SMB53 may be important for
the abnormal metabolism of type 2 diabetes.
PMID- 28701621
TI - Antipsychotic-like activity of scopoletin and rutin against the positive symptoms
of schizophrenia in mouse models.
AB - In an earlier report, we demonstrated an antipsychotic-like activity of a
methanolic extract of Morinda citrifolia Linn fruit in mouse models and
postulated the contribution of its bioactive principles, scopoletin and rutin.
Moreover, the antidopaminergic activities of scopoletin and rutin were reported
in isolated vas deferens preparations. In the present study, scopoletin and rutin
were assessed for antipsychotic-like activity using apomorphine-induced climbing
behavior and methamphetamine-induced stereotypy in mice. The results of this
study revealed that scopoletin and rutin (0.05, 0.1, 0.5, and 1 mg/kg, p.o.) had
a "U-shaped" dose-dependent effect on climbing and stereotyped behaviors induced
by apomorphine and methamphetamine, respectively, in mice. A significant
reduction in climbing and stereotyped behaviors caused by scopoletin and rutin
was observed only at a dose 0.1 mg/kg. This study suggests that scopoletin and
rutin can alleviate positive symptoms of schizophrenia only at a specific dose.
Further studies evaluating the effects of scopoletin and rutin on animal models
for negative symptoms of schizophrenia are required for a novel drug discovery in
the treatment of neuropsychiatric diseases.
PMID- 28701622
TI - Effects on glycocalyx structures of frozen-thawed bovine sperm induced by flow
cytometry and artificial capacitation.
AB - Sperm sorting by flow cytometry is a useful technology in the bovine industry,
but the conception rates after artificial insemination using sex-sorted sperm are
lower than when using the un-sorted sperm. In this study, we have investigated
the causes for these low conception rates. We have focused on changes caused by
flow cytometry to the glycocalyx, which forms the outermost surface of the sperm
membrane. We have also evaluated the effects of capacitation on the glycocalyx
since capacitation involves a redistribution of the sperm membrane that is vital
for successful fertilization and conception. Lectin histochemistry was used to
visualize the structure of the sperm glycocalyx. Lectin-staining sites were
examined in non-treated sperm, sex-sorted sperm, and capacitated sperm. We have
detected six different staining patterns related to different labeling regions of
the sperm. Phaseolus vulgaris-erythroagglutinin (PHA-E) lectin-staining patterns
of non-treated sperm were very different from those observed for sex-sorted sperm
or capacitated sperm, suggesting that both, sex sorting by flow cytometry and the
capacitation process affected the glycocalyx structures in the sperm. In
addition, the total tyrosine-phosphorylation level in sex-sorted sperm was
significantly higher than that in the non-treated sperm. Therefore, we concluded
that the unexpected capacitation of bovine sperm during flow cytometry is
associated with changes in the glycocalyx. Since premature capacitation leads to
low conception rates, this unexpected capacitation could be a cause of low
conception rates after artificial insemination using sex-sorted sperm.
PMID- 28701623
TI - Molecular characterization of the ribosomal DNA unit of Sarcocystis
singaporensis, Sarcocystis zamani and Sarcocystis zuoi from rodents in Thailand.
AB - Sarcocystis species are heteroxenous cyst-forming coccidian protozoan parasites
with a wide host range, including rodents. In this study, Sarcocystis spp.
samples were isolated from Bandicota indica, Rattus argentiventer, R. tiomanicus
and R. norvegicus across five provinces of Thailand. Two major groups of
Sarcocystis cysts were determined in this study: large and small cysts. By
sequence comparisons and phylogenetic analyses based on the partial sequences of
28S ribosomal DNA, the large cysts showed the highest identity value (99%) with
the S. zamani in GenBank database. While the small cysts could be divided into 2
groups of Sarcocystis: S. singaporensis and presupposed S. zuoi. The further
analysis on 18S rDNA supported that the 2 isolates (S2 and B6 no.2) were as
identified as S. singaporensis shared a high sequence identity with the S.
singaporensis in GenBank database and the unidentified Sarcocystis (4 isolates,
i.e., B6 no.10, B6 no.12, B10 no.4 and B10 no.7) showed 96.3-99.5% identity to S.
zuoi as well as high distinct identity from others Sarcocystis spp. (<=93%). The
result indicated that these four samples should be S. zuoi. In this study, we
provided complete sequence of internal transcribed spacer 1 (ITS1), 5.8S rDNA and
internal transcribed spacer 2 (ITS2) of these three Sarcocystis species and our
new primer set could be useful to study the evolution of Sarcocystis.
PMID- 28701624
TI - Biochemical characterization of aminopeptidase N2 from Toxoplasma gondii.
AB - Aminopeptidase N (APN) is a member of the highly conserved M1 family of
metalloproteases, and is considered to be a valuable target for the treatment of
a variety of diseases, e.g., cancer, malaria, and coccidiosis. In this study, we
identified an APN gene (TgAPN2) in the Toxoplasma gondii genome, and performed a
biochemical characterization of the recombinant TgAPN2 (rTgAPN2) protein. Active
rTgAPN2 was first produced and purified in Escherichia coli. The catalytic
activity of the enzyme was verified using a specific fluorescent substrate, H-Ala
MCA; the rTgAPN2 was relatively active in the absence of added metal ions. The
addition of some metal ions, especially Zn2+, inhibited the activity of the
recombinant enzyme. The activity of rTgAPN2 was reduced in the presence of the
EDTA chelator in the absence of added metal ions. The optimum pH for enzyme
activity was 8.0; the enzyme was active in the 3-10 pH range. The substrate
preference of rTgAPN2 was evaluated. The enzyme showed a preference for
substrates containing N-terminal Ala and Arg residues. Finally, bestatin and
amastatin were shown to inhibit the activity of the enzyme. In conclusion,
rTgAPN2 shared general characteristics with the M1 family of aminopeptidases but
also had some unique characteristics. This provides a basis for the function of
aminopeptidases and the study of drug targets.
PMID- 28701625
TI - First report of Fasciola larva infection in Galba truncatula (Muller, 1774)
(Gastropoda, Lymnaeidae) occurring in the natural environment in Hokkaido, Japan.
AB - In Hokkaido, Japan, wild sika deer are highly infected with Fasciola flukes,
suggesting that the flukes complete their life cycle via intermediate host snails
and definitive host animals occurring in the natural environment. However,
infected snails have been found only in cattle farms contaminated with
fasciolosis. This study reports the first Fasciola larva infection in Galba
truncatula snails occurring in the Shoro and Atsuma rivers in the natural
environment. Molecular analysis revealed that the nad1 haplotype of the larvae
was consistent with that of Fasciola adults obtained from sika deer in Hokkaido.
These results indicated that Fasciola flukes complete their life cycle via G.
truncatula and sika deer occurring in the natural environment.
PMID- 28701626
TI - A New Factor for Vascular Calcification in Chronic Kidney Disease: Computed
Tomography-Based Renal Parenchymal Volume.
PMID- 28701627
TI - Impact of keyboard typing on the morphological changes of the median nerve.
AB - OBJECTIVES: The primary objective was to investigate the effects of continuous
typing on median nerve changes at the carpal tunnel region at two different
keyboard slopes (0 degrees and 20 degrees ). The secondary objective was to
investigate the differences in wrist kinematics and the changes in wrist
anthropometric measurements when typing at the two different keyboard slopes.
METHODS: Fifteen healthy right-handed young men were recruited. A randomized
sequence of the conditions (control, typing I, and typing II) was assigned to
each participant. Wrist anthropometric measurements, wrist kinematics data
collection and ultrasound examination to the median nerve was performed at
designated time block. RESULTS: Typing activity and time block do not cause
significant changes to the wrist anthropometric measurements. The wrist
measurements remained similar across all the time blocks in the three conditions.
Subsequently, the wrist extensions and ulnar deviations were significantly higher
in both the typing I and typing II conditions than in the control condition for
both wrists (p<0.05). Additionally, the median nerve cross-sectional area (MNCSA)
significantly increased in both the typing I and typing II conditions after the
typing task than before the typing task. The MNCSA significantly decreased in the
recovery phase after the typing task. CONCLUSIONS: This study demonstrated the
immediate changes in the median nerve after continuous keyboard typing. Changes
in the median nerve were greater during typing using a keyboard tilted at 20
degrees than during typing using a keyboard tilted at 0 degrees . The main
findings suggest wrist posture near to neutral position caused lower changes of
the median nerve.
PMID- 28701628
TI - Study of chronic pain and its associated risk factors among Japanese industry
workers: the Quality of Working Life Influenced by Chronic pain (QWLIC) study.
AB - OBJECTIVES: This study was performed to identify the prevalence, influence, and
risk factors associated with chronic pain among Japanese industry workers.
METHODS: We investigated 2,544 participants working at a manufacturing company A,
a manufacturing company B, and 16 branch shops of a retail chain company C. The
participants responded to self-administered questionnaires related to pain.
Furthermore, data obtained from the lifestyle interview sheet of an annual health
screening examination and those obtained from the questionnaires were merged. We
analyzed the association between lifestyles, psychosocial factors, and chronic
pain. Age- and sex-adjusted odds ratios were calculated with a 95% confidence
interval using the logistic regression model. RESULTS: Of 2,544 participants,
1,914 (1,224 men and 690 women) completed the questionnaire, and the response
rate was 75.2%. The prevalence of chronic pain over 3 months was 42.7% and that
of chronic pain with work disability was 11.3%. A higher proportion of obesity,
smoking habit, insomnia, psychological stress, depressive state, workaholic
nature, low social support from supervisors and coworkers, high job demand, low
job control, and job dissatisfaction was observed in workers with chronic pain
than in workers without pain. CONCLUSIONS: Several risk factors of chronic pain
in Japanese industry workers were found. Obesity, smoking habits, sleep
disorders, workplace environment, and mental state should be taken into account
as risk factors associated with chronic pain issues and general occupational
health.
PMID- 28701629
TI - Atypical pituitary adenoma with MEN1 somatic mutation associated with
abnormalities of DNA mismatch repair genes; MLH1 germline mutation and MSH6
somatic mutation.
AB - The mechanism of pituitary tumorigenesis remains largely unknown. Lynch syndrome
is an autosomal, dominantly inherited syndrome caused by a defective mismatch
repair (MMR) mechanism involved in the development of various tumors at an early
age. In this case study, we showed the occurrence of pituitary tumors associated
with Lynch syndrome for the first time and performed genetic and
immunohistochemical analysis to evaluate the genetic aberrations that might be
related to the tumorigenesis and proliferation. A 68-year-old female patient with
Lynch syndrome due to mutL homolog 1 (MLH1) gene mutation suffered from
hypersecretion of adrenocorticotrophic hormone (ACTH), hypercortisolism and a
rapidly progressive pituitary tumor. We performed genetic analysis by whole
genome sequencing with genomic DNA of the pituitary tumor and peripheral blood
leukocytes, as well as immunohistochemical analysis of MMR proteins. Genetic
analysis revealed that the tumor had homozygous gene mutation of MEN1 associated
with pituitary tumorigenesis and mutS homolog 6 (MSH6) gene. Furthermore,
immunohistochemical analysis showed that MLH1 and MSH6 immunoexpression were
negative. We reveal for the first time that MMR abnormality could cause somatic
mutation of MEN1 and pituitary tumor occurrence is associated with Lynch
syndrome. We suggest that the identified gene mutations, especially those of MSH6
and MLH1 genes, may be involved in the pathogenesis and proliferation of
pituitary tumor. The knowledge obtained from our case study is important to
elucidate the pathogenesis and proliferation mechanisms of pituitary tumors.
PMID- 28701630
TI - Association Between Bathing and Sudden Death.
PMID- 28701631
TI - Message From the Editor-in-Chief.
PMID- 28701632
TI - Clinical Features and Gaps in the Management of Probable Familial
Hypercholesterolemia and Cardiovascular Disease.
AB - BACKGROUND: Familial hypercholesterolemia (FH) is associated with premature
atherosclerotic cardiovascular disease (ASCVD). The introduction of potent
therapeutic agents underlies the importance of improving clinical diagnosis and
treatment gaps in FH.Methods and Results:A regional database of 1,690 adult
patients with high-probability FH based on age-dependent peak-low-density
lipoprotein cholesterol (LDL-C) cut-offs and exclusion of secondary causes of
severe hypercholesterolemia, was examined to explore the clinical manifestations
and current needs in the management of ASCVD, which was present in 248 patients
(15%), of whom 83% had coronary artery disease (CAD); 19%, stroke; and 13%,
peripheral artery disease. ASCVD was associated with male gender, higher peak LDL
C, lower high-density lipoprotein cholesterol (HDL-C), and traditional risk
factor burden. Despite high-intensity statin (prescribed in 83% and combined with
ezetimibe in 42%), attainment of LDL-C treatment goals was low, and associated
with treatment intensity and drug adherence. Multivessel CAD (adjusted hazard
ratios (HR), 3.05; 95% CI: 1.65-5.64), myocardial infarction, and the presence of
>=1 traditional risk factor (HR, 2.59; 95% CI: 1.42-4.71), were associated with
repeat coronary revascularizations, in contrast with peak LDL-C >300 mg/dL (HR,
1.13; 95% CI: 0.66-1.91). CONCLUSIONS: Main manifestations of ASCVD in FH
patients were premature, multivessel CAD with need for recurrent
revascularization, associated with classical cardiovascular risk factors but not
with peak LDL-C. In spite of intensive therapy with lipid-lowering agents,
treatment gaps were significant, with low attainment of LDL-C treatment goals.
PMID- 28701633
TI - Exercise Transcutaneous Oximetry of the Buttocks, External Validation With
Computed Tomography Angiography.
PMID- 28701634
TI - Mitochondria Regulate the Differentiation of Stem Cells from Human Exfoliated
Deciduous Teeth.
AB - Stem cells from human exfoliated deciduous teeth (SHED) are isolated from the
dental pulp tissue of primary teeth and can differentiate into neuronal cells.
Although SHED are a desirable type of stem cells for transplantation therapy and
for the study of neurological diseases, a large part of the neuronal
differentiation machinery of SHED remains unclear. Recent studies have suggested
that mitochondrial activity is involved in the differentiation of stem cells. In
the present work, we investigated the neuronal differentiation machinery of SHED
by focusing on mitochondrial activity. During neuronal differentiation of SHED,
we observed increased mitochondrial membrane potential, increased mitochondrial
DNA, and elongated mitochondria. Furthermore, to examine the demand for
mitochondrial activity in neuronal differentiation, we then differentiated SHED
into neuronal cells in the presence of rotenone, an inhibitor of mitochondrial
respiratory chain complex I, and carbonyl cyanide m-chlorophenyl hydrazone
(CCCP), a mitochondrial uncoupler, and found that neuronal differentiation was
inhibited by treatment with rotenone and CCCP. These results indicated that
increased mitochondrial activity was crucial for the neuronal differentiation of
SHED.Key words: mitochondria, differentiation, stem cells, dental pulp,
exfoliated deciduous teeth.
PMID- 28701635
TI - Association Between Sleep Disturbance and New-onset Subjective Shoulder Pain in
Survivors of the Great East Japan Earthquake: A Prospective Cohort Study in
Miyagi Prefecture.
AB - The Great East Japan Earthquake (GEJE) and Tsunami devastated the northeastern
coast of Japan on March 11, 2011. This study attempted to determine whether socio
psychological factors such as sleep disturbance and psychological distress
influenced new-onset subjective shoulder pain in survivors, during the post
disaster phase of the GEJE. From November 2012 to February 2013 (2 years after
the GEJE) and November 2014 to January 2015 (4 years after the GEJE), survivors
(18 years old or over) answered self-reported questionnaires. In total, 1,454
survivors responded to the questionnaires and were thus included in this study.
New-onset subjective shoulder pain was defined as shoulder pain by encircled
response absent at 2 years, and present at 4 years after the GEJE. Two years
after the GEJE, >= 10/24 points on the Kessler Psychological Distress Scale-6,
and >= 6/24 points on the Athens Insomnia Scale defined the presence of
psychological distress and sleep disturbance, respectively. Multiple logistic
regression analysis was used to estimate the odds ratio (OR) and 95% confidence
interval (CI) of the association between new-onset subjective shoulder pain, and
psychological distress or sleep disturbance. Amongst participants, 7.2%
(105/1,454) reported new-onset subjective shoulder pain. Sleep disturbance was
significantly associated with new-onset subjective shoulder pain (OR = 1.92, 95%
CI = 1.24-2.98, P = 0.004); however, psychological distress was not (OR = 0.78,
95% CI = 0.42-1.42, P = 0.41). In conclusion, this is the first study indicating
an association between sleep disturbance and new-onset subjective shoulder pain
amongst the survivors of the GEJE.
PMID- 28701636
TI - Influence of air-powder polishing on bond strength and surface-free energy of
universal adhesive systems.
AB - The influences of air-powder polishing with glycine or sodium bicarbonate powders
on shear bond strengths (SBS) and surface-free energies of universal adhesives
were examined. Scotchbond Universal Adhesive (SU, 3M ESPE), G-Premio Bond (GP,
GC), Adhese Universal (AU, Ivoclar Vivadent), and All-Bond Universal (AB, Bisco)
were used in this study. Bovine dentin surfaces were air polished with glycine or
sodium bicarbonate powders prior to the bonding procedure, and resin pastes were
bonded to the dentin surface using universal adhesives. SBSs were determined
after 24-h storage in distilled water at 37 degrees C. Surface-free energy was
then determined by measuring contact angles using three test liquids on dentin
surfaces. Significantly lower SBSs were observed for dentin that was air-powder
polished and surface-free energies were concomitantly lowered. This study
indicated that air-powder polishing influences SBSs and surface-free energies.
However, glycine powder produced smaller changes in these surface parameters than
sodium bicarbonate.
PMID- 28701637
TI - Retention and caries-preventive effect of glass ionomer and resin-based sealants:
An 18-month-randomized clinical trial.
AB - The objective of this study was to compare the retention and caries-preventive
effect of glass ionomer (Fuji Triage) and resin-based (Clinpro) sealants among 6
9-year-old children. This split-mouth, randomized clinical trial covered 35
children/140 fully erupted permanent first molars. Evaluation was conducted by
two independent examiners after 6, 12, and 18 months and the data were compared
in relation to the children's caries risk and age groups. The Kaplan-Meier
survival method and chi-square test were used for analysis. There were no
statistically significant differences in the survival of partial and fully
retained sealants or in the survival of caries-free pits and fissures between
glass-ionomer and resin-based sealants. In terms of retention, both sealants
performed better in the younger age group at the end of the study, and showed
better caries prevention in moderate caries risk children. After 18 months, both
sealants had comparable retention and caries-preventive effects in 6-9-year old
children.
PMID- 28701638
TI - Antibacterial activity, cytotoxicity and mechanical behavior of nano-enhanced
denture base resin with different kinds of inorganic antibacterial agents.
AB - Silanized aluminum borate whiskers (ABWs) of 4 wt%, silanized zirconium dioxide
nanoparticles (nano-ZrO2) of 2 wt% were mixed with polymethyl methacrylate (PMMA)
powder to get ZrO2-ABWs/PMMA composites. Titanium dioxide (TiO2), silver
supported titanium dioxide (Ag/TiO2), silver-supported zirconium phosphate
(Novaron) and tetrapod-like zinc oxide whiskers (T-ZnOw) antibacterial agents of
3 wt% were mixed with ZrO2-ABWs/PMMA composites respectively to fabricate
standard specimens. Plaque biofilms on the specimens surface were investigated
for colony-forming units (CFUs). In addition, cytotoxicity and mechanical
behavior were evaluated. Results showed that the CFUs values of S. mutans and C.
albican biofilms on the four antibacterial composites surface were all reduced
(p<0.05) compared to the blank and control groups. The antibacterial composites
did not have an adverse effect on fibroblast growth in this study (p>0.05) except
TiO2 and Ag/TiO2 groups of undiluted extracts. The flexural strength and surface
hardness of Novaron and T-ZnOw groups were increased (p<0.05) compared to the
control group.
PMID- 28701639
TI - Synthesized mesoporous silica and calcium aluminate cement fillers increased the
fluoride recharge and lactic acid neutralizing ability of a resin-based pit and
fissure sealant.
AB - This study evaluated the effect of different types of filler in a resin-based pit
and fissure sealant on fluoride release, recharge, and lactic acid
neutralization. Resin-based sealant was incorporated with 5% w/w of the following
fillers: calcium aluminate cement (CAC), synthesized mesoporous silica (SI), a
CAC and SI mixture (CAC+SI), glass-ionomer powder (GIC), and acetic acid-treated
GIC (GICA). Sealant without filler served as control. The samples were immersed
in deionized water or a lactic acid solution and the concentration of fluoride in
the water, before and after fluoride recharge, and the lactic acid pH change,
respectively, were determined. The CAC+SI group demonstrated the highest fluoride
release after being recharged with fluoride gel. The CAC+SI group also
demonstrated increased lactic acid pH. These findings suggest that a resin-based
sealant containing synthesized mesoporous silica and calcium aluminate cement may
enhance remineralization due to fluoride release and higher pH.
PMID- 28701640
TI - The effect of five kinds of surface treatment agents on the bond strength to
various ceramics with thermocycle aging.
AB - This study evaluated the effects of ceramic surface treatment agents on shear
bond strengths to ceramic materials with and without thermocycling. Ceramic
plates were prepared from feldspathic ceramic; AAA, lithium disilicate ceramic
material; IPS e.max Press, zirconia ceramic; Lava. Ceramic surfaces were
pretreated with one of five surface treatment agents (Clearfil PhotoBond mixed
with Porcelainbond activator (PB), Clearfil SE One mixed with Porcelainbond
activator (SO), Ceramic Primer (CP), Universal Primer (UP), Scotchbond Universal
(SU)), and then a resin cement (Clapearl DC) was filled. After 0, 5,000, and
10,000 thermocycles, micro-shear bond strengths between ceramic-cement interfaces
were determined. SU exhibited significantly lower initial bond strength to AAA
and e.max than PB, SO, CP, and UP. For Lava, PB, SO, CP and SU exhibited higher
initial bond strengths than UP. Thermocycles reduced bond strengths to all the
ceramic materials with any surface treatment.
PMID- 28701641
TI - ITCH AND BRAIN FUNCTION IN ATOPIC DERMATITIS.
PMID- 28701642
TI - COUGH AND BRAIN FUNCTION: UNDERSTANDING THE CENTRAL CONTROL OF COUGH FROM A VIEW
POINT OF NONALLERGIC CHRONIC COUGH.
PMID- 28701643
TI - GUIDE TO ALLERGEN IMMUNOTHERAPY FOR MITE ALLERGY.
PMID- 28701644
TI - PERIOSTIN IN ALLERGIC DISEASES.
PMID- 28701645
TI - THE REGULATION OF AIRWAY SMOOTH MUSCLE CONTRACTION.
PMID- 28701646
TI - AN ADULT CASE OF ANAPHYLAXIS CAUSED BY ALLERGY TO JELLYFISH.
AB - A 35-year-old female, professional diver, reported nausea, vomiting, and systemic
hives 20 to 30 minutes after ingestion of antipasto made with jellyfish. Patient
reported prior episodes of swelling after stings from several different
creatures, including jelly fish. She also developed a systemic allergic reaction
after sting from an unknown creature while diving. On the initial visit to our
hospital, serum total IgE level was 545IU/ml. We extracted crude allergen from
jellyfish and evaluated allergen specific IgE antibody levels using ELISA.
Patient samples showed higher levels of jellyfish-derived allergen specific IgE
than healthy control samples. Basophils were isolated from the peripheral blood
of patient. Stimulation with jellyfish-derived allergen showed expression of
surface antigens on basophils increased in a concentration-dependent manner.
Methods using sodium dodecyl sulfate poly acrylamide gel electrophoresis and
immunoblotting showed acid-soluble collagen fraction from jellyfish contained
above 250kDa weighed protein that may have caused this current event. A
provocation test using jellyfish samples was not performed due to risk of
anaphylactic shock. The patient was diagnosed with a jellyfish allergy due to IgE
mediated anaphylaxis after ingestion. She was asked to refrain from consuming any
food containing jellyfish. IgE-mediated food allergy caused by jellyfish is rare
worldwide. Collagen was speculated to be an allergen in this study. Additional
study to detect specific allergens related to jellyfish allergy would be
particularly useful to specify disease phenotypes and individual care in future.
PMID- 28701648
TI - Erratum : STRATEGIES OF THE TREATMENT TO REFRACTORY ALLERGIC CONJUNCTIVAL
DISORDERS [Japanese Journal of Allergology Vol.65 (2016) No.8 p.994-998].
PMID- 28701647
TI - THE CASE OF A 14-YEAR-OLD BOY WHO EXPERIENCED ANAPHYLAXIS DUE TO JELLYFISH
(MASTIGIAS PAPUA) INGESTION.
AB - We report a case of jellyfish allergy diagnosed via an oral food challenge. A 14
year-old boy had no history of jellyfish stings and had been eating commercially
available jellyfish products twice yearly for the past 5-6 years. Five minutes
after eating a commercially available boiled jellyfish product (100g), he
experienced nausea, wheezing, and erythema and had visited our hospital. We
suspected an anaphylactic reaction and treated him with intramuscular adrenaline
injection, corticosteroid and antihistamine infusions, volume resuscitation, and
salbutamol sulfate inhalation, which resulted in an improvement of the symptoms.
One-month later in our hospital, we administered an oral food challenge of the
same boiled jellyfish product bought at the same grocery store to the patient.
After ingesting 14g of boiled jellyfish, he experienced erythema, wheezing,
nausea, and abdominal pain. Several reports have described anaphylaxis caused by
the ingestion of jellyfish, but the allergens in jellyfish have not been
analyzed. A skin prick test for poly-gamma-glutamic acid (PGA) which is a
component of jellyfish stings was negative. This suggests that he was sensitized
to some allergen other than PGA via a route different from that of jellyfish
sting. Our skin prick test for several kinds of edible jellyfish suggests that
allergenicity may be different for different jellyfish.
PMID- 28701649
TI - Deodorizing Substance in Black Cumin (Nigella sativa L.) Seed Oil.
AB - A deodorizing substance in black cumin (Nigella sativa L.), a spice for curry and
vegetable foods in Southwest Asia, was examined. The essential oil prepared from
the seeds of this plant exhibited strong deodorizing activity against methyl
mercaptan, which is a main factor in oral malodor. After purification with silica
gel column chromatography, the active substance in black cumin seed oil was
identified as thymoquinone. This monoterpenic quinone functions as the main
deodorizing substance in this oil against methyl mercaptan. Metabolite analysis
suggested that the deodorizing activity may be generated by the addition of a
reactive quinone molecule to methyl mercaptan. In the present study, the menthane
type quinone and phenol derivatives exhibited deodorizing activities via this
mechanism.
PMID- 28701650
TI - Characteristic Changes in the Aroma Profile of Patchouli Depending on
Manufacturing Process.
AB - Patchouli is used as an incense material and essential oil. The characteristic
odor of patchouli leaves results from the drying process used in their
production; however, there have to date been no reports on the changes in the
odor of patchouli leaves during the drying process. We investigated the aroma
profile of dried patchouli leaves using the hexane extracts of fresh and dried
patchouli leaves. We focused on the presence or absence of the constituents of
the fresh and dried extracts, and the differences in the content of the common
constituents. Fourteen constituents were identified as characteristic of dried
patchouli extract odor by gas chromatography-olfactometry analysis. The
structures of seven of the 14 constituents were determined by gas chromatography
mass spectrometry (alpha-patchoulene, seychellene, humulene, alpha-bulnesene,
isoaromadendrene epoxide, caryophyllene oxide, and patchouli alcohol). The aroma
profile of the essential oil obtained from the dried patchouli leaves was clearly
different from that of dried patchouli. The aroma profile of the essential oil
was investigated by a similar method. We identified 12 compounds as important
odor constituents. The structures of nine of the 12 constituents were determined
by gas chromatography-mass spectrometry (cis-thujopsene, caryophyllene, alpha
guaiene, alpha-patchoulene, seychellene, alpha-bulnesene, isoaromadendrene
epoxide, patchouli alcohol, and corymbolone). Comparing the odors and
constituents demonstrated that the aroma profile of patchouli depends on the
manufacturing process.
PMID- 28701651
TI - Biotransformation of (-)-(1R,4S)-Menthone and (+)-(1S,4R)-Menthone by the Common
Cutworm Spodoptera litura Larvae.
AB - Using biotransformation as a biocatalytic process has the advantage of being able
to proceed under mild conditions and with high regio- and enantioselectivity.
This study investigated the biotransformation of (-)-(1R,4S)-menthone (1) and (+)
(1S,4R)-menthone (2) by Spodoptera litura larvae. Compound 1 was converted to (-)
(1R,4S)-7-hydroxymenthone (1-1), (+)-(1R,3S,4S)-7-hydroxyneomenthol (1-2) and (-)
(1R,4S,8R)-p-menth-3-one-9-oic acid (1-3). The metabolism of substrate 2
generated three enantiomers of the above metabolites, designated as 2-1 to 2-3,
respectively. The C-9 position of (-)-menthone and (+)-menthone was oxidized to
carboxylic acid by S. litura, which is a metabolic pathway not observed in any
other example of biocatalysis.
PMID- 28701652
TI - Electrochemical Synthesis of Dihydrobenzofurans and Evaluation of Their Insect
Antifeedant Activities.
AB - Electrochemically synthesized dihydrobenzofurans were evaluated for their insect
antifeedant activities against phytophagous insects. They were prepared through
the coupling reactions of various alkenes with a phenoxy cation generated by
oxidation near the cathode in the electrolytic reaction. The insect antifeedant
activities of these synthetic dihydrobenzofurans were evaluated in the common
cutworm (Spodoptera litura) and diamond back moth (Plutella xylostella) with the
dual choice leaf disk bioassay method. The insect antifeedant activities of most
of the acetophenone-type dihydrobenzofurans were strong, while those of
derivatives with a t-butyl group were weaker. The biological activities in insect
species differed with the structural features of the compounds.
PMID- 28701653
TI - Comparative Study on Volatile Compounds of Alpinia japonica and Elettaria
cardamomum.
AB - The volatile compounds obtained from the ether extracts, headspace gases and
steam distillates of Alpinia japonica and Elettaria cardamomum were analyzed by
GC/MS. Both species were rich sources of naturally rare fenchane-type
monoterpenoids, fenchene, fenchone, fenchyl alcohol and its acetate, together
with 1,8-cineole. The distributions of volatile sesquiterpenoids were very poor
in both species. Chiralities of fenchone in A. japonica and E. cardamomum were
99% of (1S,4R)-(+)-form. Camphor in A. japonica is composed of a mixture of
(1R,4R)-(+)-form (94.3%) and (1S,4S)-(-)-form (5.7%). On the other hand, E.
cardamomum produced only (1R,4R)-(+)-camphor (99%).
PMID- 28701654
TI - Volatile Compounds from the Different Organs of Houttuynia cordata and Litsea
cubeba (L. citriodora).
AB - The volatile compounds obtained from the different organs of Houttuynia cordata
(Saururaceae) and Litsea cubeba (Lauraceae) were analyzed by Gas
Chromatography/Mass Spectrometry (GC/MS), Headspace Solid Phase Micro Extraction
Gas Chromatography/Mass Spectrometry (HS-SPME-GC/MS), and GC/olfactometry (GC/O).
The major component of all parts of H. cordata is assigned as 4-tridecanone. Each
organ produces myrcene as the major monoterpenoid. The major monoterpene in the
rhizomes and roots was beta-pinene instead of myrcene. 1-Decanal which was
responsible for the unpleasant odor of this plant, was the predominant polyketide
in both leaves and stems. The presence of 1-decanal was very poor in flowers,
stem collected in summer, rhizomes, and roots. GC/MS analyses were very simple in
case of the crude extracts of flowers. The content of sesquiterpenoids was
extremely poor. (8Z)-Heptadecene, geranial, and neral were detected as the major
components in Litsea cubeba. Odor-contributing components by GC/O analysis of the
ether extract of the fresh flowers of L. cubeba were neral and geranial which
played an important role in sweet-lemon fragrance of the flowers. The role of a
high content of (8Z)-heptadecene was still unknown but it might play a
significant role in the dispersion of the volatile monoterpene hydrocarbons and
aldehydes. The flower volatiles of the Japanese L. cubeba were chemically quite
different from those of the Chinese same species.
PMID- 28701655
TI - Preventive Effects of the Dietary Intake of Medium-chain Triacylglycerols on
Immobilization-induced Muscle Atrophy in Rats.
AB - Previous studies have shown that medium-chain triacylglycerols (MCTs) exert
favorable effects on protein metabolism. This study evaluated the effects of the
dietary intake of MCTs on rat skeletal muscle mass and total protein content
during casting-induced hindlimb immobilization, which causes substantial protein
degradation and muscle atrophy. Rats were fed a standard diet containing long
chain triacylglycerols (LCTs) or MCTs for 3 days and then a unilateral hindlimb
was immobilized while they received the same diet. After immobilization for 3, 7,
and 14 days, muscle mass and total protein content in immobilized soleus muscle
in the LCT-fed rats had markedly decreased compared to the contralateral muscle;
however, these losses were partially suppressed in MCT-fed rats. Autophagosomal
membrane proteins (LC-I and -II), which are biomarkers of autophagy-lysosome
activity, did not differ significantly between the LCT- and MCT-fed rats. In
contrast, the immobilization-induced increase in muscle-specific E3 ubiquitin
ligase MuRF-1 protein expression in immobilized soleus muscle relative to
contralateral muscle was completely blocked in the MCT-fed rats and was
significantly lower than that observed in the LCT-fed rats. Collectively, these
results indicate that the dietary intake of MCTs at least partly alleviates
immobilization-induced muscle atrophy by inhibiting the ubiquitin-proteasome
pathway.
PMID- 28701656
TI - Pedologic Factors Affecting Virgin Olive Oil Quality of "Chemlali" Olive Trees
(Olea europaea L.).
AB - The aim of this study examined the characterization of extra virgin olive oil
samples from the main cultivar Chemlali, grown in five olive orchards with
different soil type (Sandy, Clay, Stony, Brown, Limestone and Gypsum). Volatile
compounds were studied using headspace-solid phase micro-extraction (HS-SPME) and
gas chromatography-mass spectrometry (GC-MS) technics. Moreover, the sterol
profile was established using gas chromatography-mass spectrometry. 35 different
volatile compounds were identified: alcohols, esters, aldehydes, ketones and
hydrocarbons. The chemical composition of the volatile fraction was characterized
by the preeminence of 2-hexenal (32.75%) and 1-hexanol (31.88%). Three sterols
were identified and characterized. For all olive oil samples, beta-sitosterol
(302.25 mg/kg) was the most abundant sterol. Interestingly, our results showed
significant qualitative and quantitative differences in the levels of the
volatile compounds and sterols from oils obtained from olive trees grown in
different soil type.
PMID- 28701657
TI - Equation to estimate visceral adipose tissue volume based on anthropometry for
workplace health checkup in Japanese abdominally obese men.
AB - The purpose of this study was to develop a new equation model for predicting
abdominal visceral adipose tissue (VAT) volume using anthropometric values for
workplace health checkup and to clarify the association between metabolic risk
factors and measured and predicted VAT volumes. Two hundred sixty male workers
(200 for derivation group and 60 for validation group) participated in the cross
sectional study. The anthropometric variables and VAT volume were measured with
24 consecutive magnetic resonance images. Measurements in the validation group
also included metabolic risk factors, i.e. blood pressure, HDL cholesterol,
triglyceride, fasting glucose and HbA1c. Using multiple regression analyses for
the derivation group, we determined the best prediction equation for abdominal
VAT volume with a variance of 47% as follows: 47.03 age+117.79 BMI+74.18 waist
circumference -8,792.7. In our validation group, the correlation coefficient
between the measured and predicted VAT volumes was 0.74 (p<0.01). Furthermore,
blood pressure, fasting glucose and HbA1c correlated with both measured and
predicted VAT volumes. This study suggests that the equation model has potential
to assess VAT accumulation levels in workers health checkup where CT and MRI are
not available.
PMID- 28701658
TI - Drosophila DOCK Family Protein Zizimin Involves in Pigment Cell Differentiation
in Pupal Retinae.
AB - The dedicator of cytokinesis (DOCK) family proteins are known as one of guanine
nucleotide exchange factors (GEFs), that contribute to cellular signaling
processes by activating small G proteins. Although mammalian Zizimin is known to
be a GEF for Cdc42 of Rho family small GTPase, its role in vivo is not well
understood. Here we studied in vivo function of Drosophila Zizimin (Ziz).
Knockdown of Ziz in eye imaginal discs induced the rough eye phenotype
accompanied with fusion of ommatidia, loss of bristles and loss of pigments.
Immunostaining analyses revealed that Ziz mainly localizes in the secondary
pigment cells (SPCs) and tertiary pigment cells (TPCs) in pupal retinae. Ziz
knockdown induced SPC- and TPC-like cells with aberrant morphology in the pupal
retina. Delta (Dl), a downstream target of EGFR signaling is known to regulate
pigment cell differentiation. Loss-of-function mutation of Dl suppressed the
rough eye phenotype and the defect in differentiation of SPCs and TPCs in Ziz
knockdown flies. Moreover, Ziz-knockdown increased Dl expression level especially
in SPCs and TPCs. In addition, mutations of rhomboid-1 and roughoid that are
activators of EGFR signaling pathway also suppressed both the rough eye phenotype
and the defect in differentiation of SPCs and TPCs in Ziz-knockdown flies.
Activation of EGFR signaling in Ziz-knockdown flies were further confirmed by
immunostaining with anti-diphospho ERK IgG. These results indicate that Ziz
negatively regulates the Dl expression in SPCs and TPCs to control
differentiation of pigment cells and this regulation is mediated by EGFR
signaling pathway.Key words: Zizimin, DOCK, EGFR signaling pathway, pigment cell,
Drosophila.
PMID- 28701659
TI - Preface to the Special Issue for 110th Japanese Society of Medical Physics Annual
Meeting.
PMID- 28701660
TI - Precision in Wedge Off-axis Using Independent Dose Verification.
AB - It is essential for quality assurance to verify the safety of each individual
patient's plan in radiation therapy. The tolerance level for independent
verification of monitor unit calculations for non-IMRT clinical radiotherapy has
been shown in the AAPM TG114. Thus, we investigated the precision of independent
MU (dose) verification considering a wedge off-axis calculation and we conducted
a study at twelve institutes for independent verification with the wedge off-axis
calculation. The results obtained with the wedge off-axis calculation showed
better agreement with the treatment planning system calculation results than
those without the former calculation in a phantom study and in the patient
retrospective study. The confidence limits with the wedge off-axis calculation
were 2.2+/-3.4% and 2.0+/-4.3% for the plans with a physical wedge and a non
physical wedge in the patient study, respectively. However, the confidence limits
were over 5% without the off-axis calculation. From our multi-institutional
study, the results suggested that the tolerance level for the wedge off-axis plan
would be 5% when considering the wedge off-axis calculation and the level was
similar to that of the treatment planning system using other conventional
irradiation techniques.
PMID- 28701661
TI - Impact of Different Independent Dose Verification Software Programs for Secondary
Check.
AB - PURPOSE: A multi-institutional study was performed to identify the impact of
different independent dose verification programs on independent dose verification
software program. METHODS: Data for 1,543 treatment fields were collected in
three institutions. RADCALC and Simple MU Analysis (Simple MU) using the Clarkson
based algorithm were used. RADCALC needs the input of radiological path length
(RPL) from radiotherapy treatment planning systems (RTPSs) (Eclipse or
Pinnacle3). The Simple MU computes the RPL using CT images independently from the
RTPSs. Ion-chamber measurements were performed for commissioning the two programs
and the RTPSs. Next, the results of the two programs were compared to the RTPSs
obtained in the clinically-approved plans in all three institutions. RESULTS: The
commissioning results showed +/-1.5% variation in the ion-chamber measurements
and there was slight difference between the institutions. The RADCALC (0.9+/
2.2%) and the Simple MU (1.7+/-2.1%) results showed a slight systematic
difference. Pinnacle3 computed longer RPLs because it used CT-physical density
tables. Thus, there was an impact on the accuracy in the treatment plans
involving bone and other high-density materials. CONCLUSION: Dose calculation
algorithms in different dose verification programs provided similar results.
However, care must be taken because different RPL calculation methods in the
RTPSs may affect dose difference between different independent dose verification
programs by 1%.
PMID- 28701662
TI - Overview of JSPS Core-to-Core Program: Forming Research and Educational Hubs of
Medical Physics.
AB - To foster medical physicists, we introduce the achievement we made since 2011
under the national research project of the Japan Society for the Promotion of
Science (JSPS) Core-to-Core program; 'Forming Research and Educational Hubs of
Medical Physics.' On this basis and under the JSPS program, we promoted research
and educational exchange with Indiana University (IU) in USA, University of
Groningen (The UG) in the Netherland and other cooperating institutions such as
University of Minnesota (UM).A total of 23 students and researchers were sent. UG
accepted the most among three institutions. In turn, 12 foreign researchers
including post-doctor fellows came to Japan for academic seminars or educational
lectures.Fifteen international seminars were held; 8 in Japan, 4 in USA, and 3 in
the Netherland.Lots of achievement were made through these activities in 5 years.
Total of 23 research topics at the international conferences were presented.
Total of 12 articles were published in international journals.This program
clearly promoted the establishment of international collaboration, and many young
researchers and graduate students were exchanged and collaborated with foreign
researchers.
PMID- 28701663
TI - International Collaboration on Medical Physics in NIRS.
PMID- 28701664
TI - Multidimensional Image Analysis for High Precision Radiation Therapy.
AB - High precision radiation therapy (HPRT) has been improved by utilizing
conventional image engineering technologies. However, different frameworks are
necessary for further improvement of HPRT. This review paper attempted to define
the multidimensional image and what multidimensional image analysis is, which may
be feasible for increasing the accuracy of HPRT. A number of researches in
radiation therapy field have been introduced to understand the multidimensional
image analysis. Multidimensional image analysis could greatly assist clinical
staffs in radiation therapy planning, treatment, and prediction of treatment
outcomes.
PMID- 28701665
TI - The Clinical Applications of Polymer Gel Dosimetry Using MRI.
AB - Polymer gel dosimeters are devices that utilize the radiation-induced
polymerization reactions of vinyl monomers in a gel to store information of
radiation dose. They have some advantages over other dosimeters as the visual
conformation and the direct read-out of three-dimensional (3D) radiation dose
information for the dosimetric verification of intensity modulated radiotherapy
(IMRT), volumetric modulated arc therapy (VMAT), and stereotactic radiotherapy
(SRT) with steep dose gradients. In this report, the dosimetric uncertainties and
potential for clinical applications of polymer gel dosimetry by the in-house
developed 3D dose verification system for IMRT and VMAT QA is outlined.
PMID- 28701666
TI - Current Status of MR-Linac System.
AB - Current status of MR-Linac System was reported. First, we introduced the history
of development about MR-Linac System. We discussed the advantage of MR-Linac for
radiotherapy. Next, we explained the electron return effect caused by magnetic
field, resulting in different dose distribution, compared to dose distribution
with no magnetic field. Our explanation about MR-Linac will help for
understanding this system.
PMID- 28701667
TI - Series: Basic Exercises Using Excel (2).
PMID- 28701668
TI - Effects of Smoking on Ischemic Stroke, Intracranial Hemorrhage, and Coronary
Artery Events in Japanese Patients With Non-Valvular Atrial Fibrillation.
AB - The effects of smoking on the prognosis of non-valvular atrial fibrillation
(NVAF) patients are unclear.The Shinken Database 2004-11 (n = 17,517) includes
all new patients visiting the Cardiovascular Institute between June 2004 and
March 2012. Among these cases, 2,102 NVAF patients were identified. The effects
of smoking on ischemic stroke (IS), intracranial hemorrhage (ICH), and coronary
artery events including percutaneous coronary intervention (PCI) and acute
coronary syndrome (ACS) were analyzed. Smokers were younger and had lower risk
profiles compared with non-smokers. A similar tendency was observed between
current and former smokers. In contrast, patients with high tobacco consumption
were older and had higher risk profiles, including uncontrolled hypertension,
compared with those with low tobacco consumption. In 8,159 patient-years, IS,
ICH, PCI, and ACS occurred at rates of 7.7, 2.7, 12.4, and 3.0 per 1000 patient
years. In multivariate Cox regression analysis, smoking was not significantly
associated with any adverse event. However, different effects of smoking were
observed when stratified by age. In patients >= 65 years old, current smokers
were independently associated with PCI. Moreover, current smokers and smokers
with a total tobacco amount >= 800 were marginally and independently associated
with IS. In patients < 65 years, current smokers were independently associated
with ICH.Age appears to be one of the contributors to differentiation of the
effects of smoking on cardiovascular events in our NVAF patients. In elderly
patients who still smoke, smoking was associated with the promotion of
atherosclerosis or thromboembolism, whereas in young patients it was associated
with bleeding.
PMID- 28701669
TI - Muscle Weakness Is Associated With an Increase of Left Ventricular Mass Through
Excessive Blood Pressure Elevation During Exercise in Patients With Hypertension.
AB - Autonomic imbalance in hypertension induces excessive blood pressure (BP)
elevation during exercise, thereby increasing left ventricular mass (LVM).
Although muscle weakness enhances autonomic imbalance by stimulating muscle
sympathetic activity during exercise, it is unclear whether muscle weakness is
associated with an increase of LVM in patients with hypertension. This study
aimed to investigate the relationships between muscle weakness, BP elevation
during exercise, and LVM in these patients. Eighty-six hypertensive patients aged
69 +/- 8 years with controlled resting BP (ie, < 140/90 mmHg) were recruited.
Plasma brain natriuretic peptide (BNP), left ventricular mass index (LVMI), and
knee extension muscle strength were measured. Changes in plasma noradrenaline
(NORA) and brachial-ankle pulse wave velocity (ba-PWV) were assessed before and
after an ergometer exercise test performed at moderate intensity (DeltaNORA and
DeltaPWV, respectively). A difference between baseline and peak systolic BP
during the exercise test was defined as BP elevation during exercise (DeltaSBP).
Relationships between muscle strength, DeltaNORA, DeltaPWV, DeltaSBP, BNP, and
LVMI were analyzed, and significant factors increasing LVM were identified using
univariate and multivariate regression analyses. Muscle strength was negatively
correlated with DeltaNORA (r = -0.202, P = 0.048), DeltaPWV (r = -0.328, P =
0.002), DeltaSBP (r = -0.230, P = 0.033), BNP (r = -0.265, P = 0.014), and LVMI
(r = -0.233, P = 0.031). LVMI was positively correlated with DeltaPWV (r = 0.246,
P = 0.023) and DeltaSBP (r = 0.307, P = 0.004). Muscle strength was a significant
independent factor associated with LVMI (beta = -0.331, P = 0.010). Our findings
suggest that muscle weakness is associated with an increase of LVM through
excessive BP elevation during exercise in patients with hypertension.
PMID- 28701670
TI - Impact of Compound Hypertonic Saline Solution on Decompensated Heart Failure.
AB - The aim of the present study was to evaluate the effects of hypertonic saline
solution (C-HSS) with high dose furosemide on hospitalization time, readmission,
and mortality in patients with New York Heart Association (NYHA) class III heart
failure.Decompensated heart failure patients (NYHA III) with chronic ischemic or
nonischemic cardiomyopathy and ejection fraction < 40% were divided into 2 groups
in an open-label random manner: the first group received a 1-hour intravenous
infusion of furosemide (100 mg) plus compound C-HSS (100 mL) twice daily and
underwent serious water restriction (500 mL/day); the second group received
furosemide intravenous bolus (100 mg) twice a day and water restriction (500
mL/day), without C-HSS. Both groups had normal sodium (120 mmol sodium) intake.
After discharge, the two groups continued to receive 120 mmol Na/day and 500-1000
mL water/day.The first group (132 C-HSS patients) had an increase in urination, a
reduction in hospitalization time (4 +/- 2 versus 7 +/- 2 days, P < 0.01), and a
reduction in hospitalization costs (2210 RMB versus 3506 RMB, P < 0.01) compared
with the second group (132 without C-HSS patients). During the follow-up period
(36 +/- 12 months), the first group had a significantly higher average
readmission time (31.84 +/- 7.58 months versus 15.60 +/- 6.25 months, P < 0.01)
and lower mortality rate (16.5% versus 31.9%, P < 0.01).The results suggest that
periodical C-HSS administration, combined with serious water restriction and a
normal sodium diet, significantly reduces the hospitalization time, readmission
rate, and mortality in patients with NYHA class III HF.
PMID- 28701671
TI - Is Serum Uric Acid Independently Associated With Left Ventricular Mass Index,
Ejection Fraction, and B-Type Natriuretic Peptide Among Female and Male Cardiac
Patients?
AB - Mean serum uric acid (SUA) levels are higher in men than women. In addition,
recent studies have suggested that the SUA threshold at which the cardiovascular
risk might increase may vary between women and men. In the current retrospective
study, by analyzing the data from 219 female and 519 male patients who were free
from uric acid-lowering medication, we investigated whether SUA is associated
with left ventricular mass index (LVMI), left ventricular ejection fraction
(LVEF), and plasma levels of B-type natriuretic peptide (BNP) independent of
confounding factors, such as serum calcium, inorganic phosphate, and fibroblast
growth factor 23 (FGF23), in a gender-specific manner.In multivariate stepwise
linear regression analysis in which age, blood pressure, eGFR, corrected calcium,
inorganic phosphate, and FGF23 were entered as potential covariates, SUA was
selected as a factor significantly associated with LVEF, LVMI, and plasma levels
of BNP in both genders. On the other hand, however, after adding diuretic use as
a potential covariate, the association between SUA and LVEF lost statistical
significance in both genders, and that between SUA and BNP lost significance
among female patients. These findings suggest that diuretic use is a non
negligible confounder in understanding the observed association between SUA and
cardiac dysfunction and heart failure.In summary, SUA is associated with left
ventricular hypertrophy independent of confounding factors including FGF23 and
diuretic use in female and male patients. Whether lowering SUA can influence the
progression of cardiac remodeling awaits further investigation.
PMID- 28701672
TI - The Shortest QRS Duration of an Electrocardiogram Might Be an Optimal
Electrocardiographic Predictor for Response to Cardiac Resynchronization Therapy.
AB - QRS duration has been associated with the response to cardiac resynchronization
therapy (CRT). However, the methods for defining QRS duration to predict the
outcome of CRT have discrepancies in previous reports. The aim of this study was
to determine an optimal measurement of QRS duration to predict the response to
CRT.Sixty-one patients who received CRT were analyzed. All patients had class III
IV heart failure, left ventricular ejection fraction not more than 35%, and
complete left bundle branch block. The shortest, longest, and average QRS
durations from the 12 leads of each electrocardiogram (ECG) were measured. The
responses to CRT were determined using the changes in echocardiography after 6
months. Thirty-five (57.4%) patients were responders and 26 (42.6%) patients were
non-responders. The pre-procedure shortest, average, and longest QRS durations
and the QRS shortening (DeltaQRS) of the shortest QRS duration were significantly
associated with the response to CRT in a univariate logistic regression analysis
(P = 0.002, P = 0.03, P = 0.04 and P = 0.04, respectively). Based on the
measurement of the area under curve of the receiver operating characteristic
curve, only the pre-procedure shortest QRS duration and the DeltaQRS of the
shortest QRS duration showed significant discrimination for the response to CRT
(P = 0.002 and P = 0.038, respectively). Multivariable logistic regression showed
the pre-procedure shortest QRS duration is an independent predictor for the
response to CRT.The shortest QRS duration from the 12 leads of the
electrocardiogram might be an optimal measurement to predict the response to CRT.
PMID- 28701673
TI - Pulmonary Artery Diameter Predicts Lung Injury After Balloon Pulmonary
Angioplasty in Patients With Chronic Thromboembolic Pulmonary Hypertension.
AB - Balloon pulmonary angioplasty (BPA) has been an attractive strategy for chronic
thromboembolic pulmonary hypertension (CTEPH), even though it occasionally causes
lung injury. However, predictive factors of lung injury after BPA have not been
established. Pulmonary artery (PA) dilatation is often observed in patients with
pulmonary hypertension. We investigated the association between PA diameter and
complications after BPA.The subjects were 19 CTEPH patients who underwent BPA.
Patients were divided into two groups: patients with lung injury including
asymptomatic lung infiltration on computed tomography (CT) images or mild
hemoptysis (group L, n = 9) and no complications (group N, n = 10). PA diameter
was measured on CT and corrected by the body surface area (PA diameter
index).There were no significant differences in hemodynamic indices or the number
of treated vessels between the two groups. Right, left, and main PA diameter
indices were higher in group L than in group N. Among the clinical variables, the
right, left, and main PA diameter indices were significant predictors for lung
injury caused by BPA (right PA: OR 1.819, 95%CI 1.056-3.135, P < 0.05; left PA:
OR 1.857, 95%CI 1.091-3.159, P < 0.05; main PA: OR 1.399, 95%CI 1.001-1.956, P <
0.05).The PA diameter index can be used to effectively predict the risk of lung
injury after BPA.
PMID- 28701674
TI - Resveratrol Ameliorates Arterial Stiffness Assessed by Cardio-Ankle Vascular
Index in Patients With Type 2 Diabetes Mellitus.
AB - Resveratrol has been reported to have potent anti-atherosclerotic effects in
animal studies. However, there are few interventional studies in human patients
with atherosclerogenic diseases. The cardio-ankle vascular index (CAVI) reflects
arterial stiffness and is a clinical surrogate marker of atherosclerosis. The aim
of the present study was to investigate the effect of resveratrol on arterial
stiffness assessed by CAVI in patients with type 2 diabetes mellitus (T2DM).In
this double-blind, randomized, placebo-controlled study, 50 patients with T2DM
received supplement of a 100mg resveratrol tablet (total resveratrol: oligo
stilbene 27.97 mg/100 mg/day) or placebo daily for 12 weeks. CAVI was assessed at
baseline and the end of study. Body weight (BW), blood pressure (BP), glucose and
lipid metabolic parameters, and diacron-reactive oxygen metabolites (d-ROMs; an
oxidative stress marker) were also measured.Resveratrol supplementation decreased
systolic BP (-5.5 +/- 13.0 mmHg), d-ROMs (-25.6 +/- 41.8 U.CARR), and CAVI (-0.4
+/- 0.7) significantly (P < 0.05) and decreased BW (-0.8 +/- 2.1 kg, P = 0.083)
and body mass index (-0.5 +/- 0.8 kg/m2, P = 0.092) slightly compared to
baseline, while there were no significant changes in the placebo group. Decreases
in CAVI and d-ROMs were significantly greater in the resveratrol group than in
the placebo group. Multivariate logistic regression analysis identified
resveratrol supplementation as an independent predictor for a CAVI decrease of
more than 0.5.In conclusion, 12-week resveratrol supplementation may improve
arterial stiffness and reduce oxidative stress in patients with T2DM. Resveratrol
may be beneficial in preventing the development of atherosclerosis induced by
diabetes. However, a large-scale cohort study is required to validate the present
findings.
PMID- 28701675
TI - Pathology of Neointimal Calcification in Very Late Restenosis After Bare Metal
Stent Implantation for Superficial Femoral Artery.
AB - A 60-year-old man, who had claudication in his right limb due to total occlusion
of the right superficial femoral artery, received bare metal stents. Although the
bare metal stents in the superficial femoral artery did not show restenosis 5
years after stent implantation, angiography revealed significant in-stent
restenosis when he developed right critical limb ischemia at 8 years post
implantation. Ballooning for in-stent lesions did not result in full expansion.
His right limb was amputated above the knee due to progressive limb ischemia. In
the pathological findings in the superficial femoral artery, marked calcification
was observed in the entire circumference of the luminal surface of the neointima.
However, lipid core formation was not identified in the neointima. Although
several cracks following balloon angioplasty were observed at the superficial
calcified layers, injury to neointimal tissue such as compression was not
observed. The neointima exhibited heavy calcification in the very late phase of
in-stent restenosis after bare metal stent implantation in superficial femoral
artery. Therefore, balloon angioplasty in the very late phase of in-stent
restenosis potentially results in underexpansion.
PMID- 28701676
TI - Efficacy and Safety of Triple Therapy and Dual Therapy With Direct Oral
Anticoagulants Compared to Warfarin.
AB - The efficacy and safety of direct oral anticoagulants (DOAC) with antiplatelet
therapy compared to warfarin are unclear. The subjects were 280 patients who
received antiplatelet therapy with oral anticoagulation (OAC) for the treatment
of or protection from thromboembolism between January 2012 and September 2015.
Among the 280 subjects, 79 (28.2%) received dual therapy (OAC plus aspirin or
P2Y12 inhibitor) with DOAC, 75 (26.8%) dual therapy with warfarin, 46 (16.4%)
triple therapy (OAC plus aspirin and P2Y12 inhibitor) with DOAC, and 80 (28.6%)
triple therapy with warfarin.Compared to triple therapy with warfarin, triple
therapy with DOAC had slightly lower bleeding (3.5 versus 12.0/100 persons-years,
HR: 0.24, 95%CI: 0.03 to 1.96, P = 0.183), and similar benefit outcomes (cardiac
death, acute myocardial infarction or stroke) and thromboembolism (7.0 versus
10.5, HR: 0.53, 95%CI: 0.10 to 2.75, P = 0.453; 7.0 versus 7.5, HR: 0.96, 95%CI:
0.18 to 5.22, P = 0.964, respectively). Compared to dual therapy with warfarin,
dual therapy with DOAC had slightly lower bleeding (3.0 versus 8.4, HR: 0.38,
95%CI: 0.07 to 2.18, P = 0.279), and similar benefit outcomes and thromboembolism
(4.6 versus 4.2, HR: 1.66, 95%CI: 0.30 to 9.25, P = 0.565; 4.6 versus 1.4, HR:
3.11, 95%CI: 0.23 to 42.84, P = 0.397, respectively). Bleeding mainly occurred
after 3 months (16/17, 94.1%).Triple therapy and dual therapy with DOAC were not
inferior to triple therapy and dual therapy with warfarin in terms of major
bleeding, benefit outcomes, and thromboembolism. Bleeding mainly occurred in the
late phase.
PMID- 28701677
TI - Mechanisms of Diuresis for Acute Decompensated Heart Failure by Tolvaptan.
AB - Tolvaptan, a vasopressin type 2 receptor antagonist, does not affect kidney
circulation or cause worsening of renal function (WRF) in patients with acute
decompensated heart failure (ADHF). Bioelectrical impedance analysis (BIA) can be
used to evaluate intravascular volume by calculating the ratio of extracellular
water (ECW) to intracellular water (ICW). There have been no reports examining
the mechanisms of tolvaptan-induced diuresis using BIA. We investigated whether
tolvaptan decreases excess volume while maintaining intravascular volume in ADHF
patients.Study patients included 29 ADHF patients (age 48-95, men 69%) diagnosed
between April 2013 and May 2016 and who underwent BIA before and after treatment.
Fifteen patients were treated with tolvaptan in addition to conventional diuresis
therapy (tolvaptan group), and 14 patients were treated with conventional
diuresis therapy only (control group). In the control group, the numerical value
of serum creatinine (Cre) significantly increased from 0.89 +/- 0.22 mg/ dL to
1.07 +/- 0.29 mg/dL (P = 0.004), and the ECW/ICW significantly decreased from
0.696 +/- 0.036 to 0.673 +/- 0.032 (P = 0.004). These values were not
significantly different from those obtained for the tolvaptan group. Furthermore,
regression analysis showed a negative correlation between DeltaCre and
DeltaECW/ICW, which are the differences between values before and after treatment
(DeltaCre = -0.002-5.668 * DeltaECW/ICW, r2 = 0.306, P = 0.002).Our findings
suggest that WRF is caused by a reduction in intravascular volume and that
tolvaptan treatment can decrease the excess volume while maintaining
intravascular volume.
PMID- 28701678
TI - Paget-Schroetter Syndrome in a Baseball Pitcher.
AB - Paget-Schroetter syndrome (PSS) is thrombosis of the deep veins draining the
upper extremity due to anatomic abnormalities of the thoracic outlet that cause
subclavian compression and subsequent thrombosis, leading to thrombus formation
in the subclavian vein. Vigorous arm activity in sports is a known risk factor.
Here, we report a case of Paget-Schroetter syndrome in a 31-year-old male non
professional baseball pitcher.
PMID- 28701679
TI - Nanoparticle-Mediated Delivery of Pitavastatin to Monocytes/Macrophages Inhibits
Left Ventricular Remodeling After Acute Myocardial Infarction by Inhibiting
Monocyte-Mediated Inflammation.
AB - Left ventricular (LV) remodeling after myocardial infarction (MI) causes heart
failure. Although medical therapies including angiotensin converting enzyme
inhibitors show inhibitory effects on post-infarct LV remodeling, the prognosis
of patients with post-infarct heart failure is still poor. Accumulating evidence
suggests that an inflammatory response is implicated in the process of post
infarct LV remodeling. Therefore, we hypothesized that anti-inflammatory therapy
by nanoparticle-mediated monocyte/macrophage-targeting delivery of pitavastatin
may protect the heart from post-infarct LV remodeling.Male C57BL/6 mice were
subjected to permanent coronary ligation and pitavastatin-incorporating
nanoparticles (Pitavastatin-NPs) were intravenously injected for 3 to 5
consecutive days. Pitavastatin-NPs were delivered to CD11b+
monocytes/macrophages, but not to cardiomyocytes. Treatment with Pitavastatin-NPs
after establishment of MI attenuated post-infarct LV remodeling accompanied by a
reduction of monocytes/macrophages in the heart, whereas pitavastatin solution
treatment did not. Pitavastatin-NPs inhibited mobilization of monocytes from the
spleen after MI. In mice after splenectomy, Pitavastatin-NPs still decreased the
number of monocytes/macrophages in the infarcted heart and inhibited post-infarct
LV remodeling.Nanoparticle-mediated delivery of pitavastatin to
monocytes/macrophages may be a novel therapeutic strategy to protect the heart
from post-infarct LV remodeling. Inhibition of monocyte mobilization from the
bone marrow is one of the major mechanisms by which Pitavastatin-NPs attenuated
post-infarct LV remodeling.
PMID- 28701680
TI - Right Ventricular End-Diastolic Pressure Is a Key to the Changes in Cardiac
Output During Adaptive Servo-Ventilation Support in Patients With Heart Failure.
AB - Adaptive servo-ventilation (ASV) is a recently-developed non-invasive therapy
that improves the clinical course of heart failure (HF) patients. However, the
precise hemodynamic response and predictors of ASV therapy remain uncertain.
Overall, 69 patients with New York Heart Association HF class II-IV underwent 10
minute ASV testing along with hemodynamic studies. Among them, 21 (30%) achieved
an acute response, which was defined as an increase in the cardiac index (CI)
during ASV. DeltaLeft ventricular end-diastolic pressure (LVEDP) did not
correlate with DeltaCI, whereas Deltatransmural LVEDP, which was calculated by
subtracting right ventricular end-diastolic pressure (RVEDP) from LVEDP, and
DeltaCI were positively correlated, similar to the ascending limb of Frank
Starling's law (P = 0.009, r = 0.311). Among baseline data, higher RVEDP and
higher LVEDP were significant predictors of an acute response by logistic
regression analyses (P < 0.05 for both). RVEDP had a significantly higher area
under the curve than LVEDP in the receiver operating characteristic analyses
(0.846 versus 0.673, P = 0.028). Higher baseline RVEDP was significantly
associated with a greater decrease in RVEDP during ASV (P < 0.001, r = -0.604).
In conclusion, in HF patients with elevated RVEDP, ASV increased cardiac output
through a decrease in RVEDP and an increase in transmural LVEDP, according to the
ascending limb of Frank-Starling's law.
PMID- 28701681
TI - Inflammation Is Associated With Platelet Coagulation Function Rather Than
Enzymatic Coagulation Function in Patients With Takayasu Arteritis.
AB - The integral changes of coagulation and fibrinolysis, and their relationships
with inflammation in patients with Takayasu arteritis (TA) remain undetermined.
The purpose of this study was to analyze the changes of coagulation and
fibrinolysis process in patients with TA by thrombelastography (TEG).A total of
127 patients with TA and 55 healthy controls were enrolled. Patients with TA were
grouped according to disease activity. The routine hematological parameters,
traditional coagulation assays, and TEG parameters were summarized
retrospectively.A shorter K time, larger alpha angle, and higher levels of MA,
MA(A), G, and TPI were found in patients with TA, especially in those at the
active stage. The R time, EPL, LY30, and CL30 were similar between patients with
TA and healthy controls, as well as TA patients with different disease activity.
Spearman's correlation showed that ESR was correlated with PLT (r = 0.206, P =
0.020), K (r = -0.353, P < 0.001), alpha angle (r = 0.328, P < 0.001), MA (r =
0.474, P < 0.001), MA (A) (r = 0.623, P < 0.001), G (r = 0.475, P < 0.001), and
TPI (r = 0.458, P < 0.001).In conclusion, inflammation was associated with
platelet coagulation function rather than enzymatic coagulation function in
patients with TA. Physicians should focus on antiplatelet treatment for improving
the prognosis of patients with TA.
PMID- 28701682
TI - Prognostic Impact of Segmental Wall Motion Abnormality in Patients With
Idiopathic Dilated Cardiomyopathy.
AB - The clinical impact of left ventricular (LV) segmental wall motion abnormalities
(SWMA) in patients with idiopathic dilated cardiomyopathy (IDCM) has not been
well elucidated.Among 100 consecutive IDCM patients with follow-up visits, we
enrolled 85 after excluding those with left bundle branch block and/or
ventricular pacemaker implantation. LV wall motion was assessed using left
ventriculography scored for 7 segments according to the American Heart
Association classification as follows: 0, normokinesis; 1, hypokinesis; 2,
akinesis; and 3, dyskinesis. SWMA were defined as a score dispersion of more than
1 degree among the segments.SWMA was exhibited by 26 patients. Kaplan-Meier
curves demonstrated that the patients with SWMA (SWMA+) had a significantly
higher cardiac event-free rate than the patients without SWMA (P < 0.001). Cox
proportional hazards analysis showed that SWMA+ was an independent predictor of
cardiac events (P = 0.03; hazard ratio = 3.38; 95% confidence interval [CI], 1.11
10.8). Furthermore, multiple regression analysis showed that SWMA+ was an
independent predictor of decreased LV end-systolic dimension index after optimal
pharmacotherapy (beta = -0.24; 95%CI, -9.12 to -0.73; P = 0.02).SWMA is common in
patients with IDCM and is independently associated with a poor prognosis and less
morphometric and functional improvement of LV in response to pharmacotherapy.
PMID- 28701683
TI - Efficacy and safety of octreotide for the treatment of congenital
hyperinsulinism: a prospective, open-label clinical trial and an observational
study in Japan using a nationwide registry.
AB - Octreotide, a long-acting somatostatin analog, has been used for treating
hypoglycemia caused by congenital hyperinsulinism (CHI). However, octreotide has
not been evaluated in clinical trials and has not been approved in any developed
country. We aimed to test the efficacy and safety of octreotide for diazoxide
unresponsive CHI through a combination of a single-arm, open-label clinical trial
(SCORCH study) and an observational study to collect data on the clinical course
of patients treated off-label in Japan (SCORCH registry). In the SCORCH study, 5
patients were stabilized (blood glucose > 45 mg/dL) by hypertonic glucose
infusion, and treated by continuous subcutaneous octreotide infusion at a dose of
5-25 MUg/kg/day. Continuous blood glucose monitoring was performed between -24
and +48 hours. In 3 patients, a clinically meaningful rise in blood glucose was
achieved and therapy was continued. The glucose infusion was gradually decreased
and stopped after 5, 11, and 174 days, respectively. In one case, remission of
CHI was reached after 606 days and octreotide was discontinued. The SCORCH
registry included 19 diazoxide-unresponsive patients treated by subcutaneous
octreotide, by continuous infusion or multiple daily injections. Of the 17
patients treated with hypertonic glucose infusion, the infusion rate was reduced
after 4 weeks to less than 50% in 11 patients (64.7%) and stopped in 9 (52.9%).
During the combined observation period of 695.4 patient-months in both studies,
no severe adverse events related to octreotide were observed. In conclusion,
subcutaneous octreotide injection was effective and well tolerated in the
majority of patients with diazoxide-unresponsive CHI.
PMID- 28701684
TI - Expression of aldo-keto reductase family 1, member C14 during ovulation in the
rat.
AB - The potent androgen 5alpha-dihydrotestosterone is metabolized to the weak
androgen 5alpha-androstane-3alpha, 17beta-diol (3alpha-diol) by the enzyme aldo
keto reductase family 1, member C14 (Akr1c14) in rodents. The purpose of the
present study was to investigate the regulation of Akr1c14 expression during the
ovulatory process in rat ovaries. Northern blot analysis revealed that treatment
of immature rats with equine chorionic gonadotropin resulted in lowered Akr1c14
expression, whereas subsequent treatment with human chorionic gonadotropin (hCG)
increased ovarian Akr1c14 expression within 3 h. In situ hybridization analysis
showed that Akr1c14 mRNA was localized in granulosa cells of growing follicles
before hCG treatment, but it was also expressed in granulosa cells of
preovulatory follicles after hCG treatment. Akr1c14 protein expression increased
after 6 h of hCG treatment and was sustained at high levels until 12 h. The
levels of 3alpha-diol in preovulatory follicles isolated from ovaries in vivo
were fluctuated by hCG treatment; decreased at 6 h and increased at 9 h. Human CG
induced Akr1c14 expression was suppressed by treatment with the progesterone
receptor antagonist RU486, but not with the cyclooxygenase inhibitor
indomethacin. Taken together, these findings demonstrate the induction of Akr1c14
by hCG in granulosa cells of rat preovulatory follicles that was regulated by
progesterone receptor antagonist.
PMID- 28701685
TI - Long Non-Coding RNA (LncRNA) HOXA11-AS Promotes Breast Cancer Invasion and
Metastasis by Regulating Epithelial-Mesenchymal Transition.
AB - BACKGROUND To detect the expression of lncRNA HOXA11-AS and its biological effect
in breast cancer. MATERIAL AND METHODS In this study, fluorescent quantitative
real-time PCR (qRT-PCR), MTT assay and clone formation assay, flow cytometry,
Transwell assay and wound healing assay, immunofluorescence, and Western blot
analysis were conducted to detect the expression of lncRNA HOXA11-AS, cell
proliferation activity, cell apoptosis rate and cell cycle distribution, the
changes of cell invasion and metastasis capacity, and the expressions of
molecular markers of epithelial-mesenchymal transition (EMT), respectively.
Additionally, a nude mouse metastatic tumor model was established to study the
influence of lncRNA HOXA11-AS on invasion and metastasis capacity of breast
cancer cells. RESULTS The qRT-PCR experiment results showed that HOXA11-AS
expression in breast cancer tissue of 50 patients was relatively higher than that
in tissue adjacent to cancer. MTT assay suggested that tumor cell proliferation
capacity was suppressed followed by the knockdown of lncRNA HOXA11-AS expression
in MDA-MB-231 and MCF-7 cells; flow cytometry results demonstrated that
interfering in lncRNA HOXA11-AS could induce tumor cell apoptosis and promote
cell cycle progression to be arrested in G1/G0 stage; experiments in vivo/vitro
manifested that interfering in lncRNA HOXA11-AS could inhibit tumor cell invasion
and migration capacity by affecting the expressions of EMT-related molecular
markers (E-cadherin, N-cadherin, Vimentin). CONCLUSIONS High expression of lncRNA
HOXA11-AS promotes breast cancer invasion and metastasis by affecting EMT, and
interfering in lncRAN HOXA11-AS expression provides a theoretical basis and
important molecular target for inhibiting the distant metastasis of breast cancer
in clinical practice.
PMID- 28701686
TI - Congestive Heart Failure with Preserved Ejection Fraction in a Patient with Light
Chain (AL) Amyloidosis and Multiple Myeloma.
AB - BACKGROUND Amyloidosis is characterized by tissue deposition of insoluble
fibrillar proteins and it affects almost every organ; there are many types and
the heart can be affected in all of them. CASE REPORT Our report describes a
middle-aged man who presented to the Emergency Department with congestive heart
failure. Clinical, electrocardiographic, and echocardiographic findings suggested
the presence of an infiltrative disease, so an abdominal fat tissue biopsy was
performed. A final diagnosis of systemic amyloidosis with heart involvement was
made. CONCLUSIONS This case highlights the importance of combining clinical,
electrocardiographic, and echocardiographic information in the diagnosis of
complex diseases like amyloidosis with heart involvement.
PMID- 28701687
TI - The temperature sensitivity of soil organic carbon decomposition is greater in
subsoil than in topsoil during laboratory incubation.
AB - The turnover of soil organic carbon (SOC) in cropland plays an important role in
terrestrial carbon cycling, but little is known about the temperature sensitivity
(Q 10) of SOC decomposition below the topsoil layer of arable soil. Here, samples
of topsoil (0-20 cm) and subsoil (20-40 cm) layers were obtained from paddy
fields and upland croplands in two regions of China. Using a sequential
temperature changing method, soil respiration rates were calculated at different
temperatures (8 degrees C to 28 degrees C) and fitted to an exponential
equation to estimate Q 10 values. The average SOC decomposition rate was 59% to
282% higher in the topsoil than in the subsoil layer because of higher labile
carbon levels in the topsoil. However, Q 10 values in the topsoil layer (5.29 +/-
1.47) were significantly lower than those in the subsoil layer (7.52 +/- 1.84).
The pattern of Q 10 values between the topsoil and subsoil was significantly
negative to labile carbon content, which is consistent with the carbon quality
temperature hypothesis. These results suggest that the high temperature
sensitivity of SOC decomposition in the subsoil layer needs to be considered in
soil C models to better predict the responses of agricultural SOC pools to global
warming.
PMID- 28701688
TI - A New Paradigm for Understanding and Enhancing the Critical Heat Flux (CHF)
Limit.
AB - Nearly a century of research on enhancing critical heat flux (CHF) has focused on
altering the boiling surface properties such as its nucleation site density,
wettability, wickability and heat transfer area. But, a mechanism to manipulate
dynamics of the vapor and liquid interactions above the boiling surface as a
means of enhancing CHF has not been proposed. Here, a new approach is implemented
to limit the vapor phase lateral expansion over the heat transfer surface and
actively control the surface wetted area fraction, known to decline monotonically
with increasing heat flux. This new degree of freedom has enabled reaching
unprecedented CHF levels and revealed new details about the physics of CHF. The
impact of wickability, effective heat transfer area, and liquid pressure on CHF
is precisely quantified. Test results show that, when rewetting is facilitated,
the CHF increases linearly with the effective surface heat transfer area. A
maximum CHF of 1.8 kW/cm2 was achieved on a copper structure with the highest
surface area among all tested surfaces. A model developed based on the
experimental data suggests that the thermal conductivity of the surface
structures ultimately limits the CHF; and a maximum CHF of 7-8 kW/cm2 may be
achieved using diamond surface structures.
PMID- 28701689
TI - Lybatides from Lycium barbarum Contain An Unusual Cystine-stapled Helical Peptide
Scaffold.
AB - Cysteine-rich peptides (CRPs) of 2-6 kDa are generally thermally and
proteolytically stable because of their multiple cross-bracing disulfide bonds.
Here, we report the discovery and characterization of two novel cystine-stapled
CRPs, designated lybatide 1 and 2 (lyba1 and lyba2), from the cortex of Lycium
barbarum root. Lybatides, 32 to 33 amino acids in length, are hyperstable and
display a novel disulfide connectivity with a cysteine motif of C-C-C-C-CC-CC
which contains two pairs of adjacent cysteines (-CC-CC). X-ray structure analysis
revealed the presence of a single cystine-stabilized (alpha + pi)-helix in lyba2,
a rare feature of CRPs. Together, our results suggest that lybatides, one of the
smallest four-disulfide-constrained plant CRPs, is a new family of CRPs.
Additionally, this study provides new insights into the molecular diversity of
plant cysteine-rich peptides and the unusual lybatide scaffold could be developed
as a useful template for peptide engineering and therapeutic development.
PMID- 28701690
TI - Charge screening strategy for domain pattern control in nano-scale ferroelectric
systems.
AB - Strain engineering is a widespread strategy used to enhance performance of
devices based on semiconductor thin films. In ferroelectrics strain engineering
is used to control the domain pattern: When an epitaxial film is biaxially
compressed, e.g. due to lattice mismatch with the substrate, the film displays
out-of-plane, often strongly enhanced polarization, while stretching the film on
the substrate results in in-plane polarization. However, this strategy is of a
limited applicability in nanorods because of the small rod/substrate contact
area. Here we demonstrate another strategy, in which the polar axis direction is
controlled by charge screening. When charge screening is maintained by bottom and
top metallization, the nanorods display an almost pure c-domain configuration
(polarization perpendicular to the substrate); when the sidewalls of the nanorods
are metallized too, a-domain formation prevails (polarization parallel to the
substrate). Simulations of the depolarization fields under various boundary
conditions support the experimental observations. The employed approach can be
expanded to other low-dimensional nano-scale ferroelectric systems.
PMID- 28701691
TI - Spatiotemporal expression profiling of long intervening noncoding RNAs in
Caenorhabditis elegans.
AB - To better understand the biological function of long noncoding RNAs, it is
critical to determine their spatiotemporal expression patterns. We generated
transgenic reporter strains for 149 out of the 170 annotated C. elegans long
intervening noncoding RNAs (lincRNAs) and profiled their temporal activity. For
the 68 lincRNAs with integrated reporter lines, we profiled their expression at
the resolution of single cells in L1 larvae, and revealed that the expression of
lincRNAs is more specific, heterogeneous and at lower level than transcription
factors (TFs). These expression patterns can be largely attributed to
transcriptional regulation because they were observed in assays using reporters
of promoter activity. The spatial expression patterns of the 68 lincRNAs were
further examined in 18 tissue categories throughout eight developmental stages.
We compared the expression dynamics of lincRNAs, miRNAs and TFs during
development. lincRNA and miRNA promoters are less active at embryo stage than
those of TFs, but become comparable to TFs after embryogenesis. Finally, the
lincRNA gene set shows a similar tissue distribution to that of miRNAs and TFs.
We also generated a database, CELE, for the storage and retrieval of lincRNA
reporter expression patterns and other relevant information. The data and strains
described here will provide a valuable guide and resource for future functional
exploration of C. elegans lincRNAs.
PMID- 28701692
TI - Next Generation Driver for Attosecond and Laser-plasma Physics.
AB - The observation and manipulation of electron dynamics in matter call for
attosecond light pulses, routinely available from high-order harmonic generation
driven by few-femtosecond lasers. However, the energy limitation of these lasers
supports only weak sources and correspondingly linear attosecond studies. Here we
report on an optical parametric synthesizer designed for nonlinear attosecond
optics and relativistic laser-plasma physics. This synthesizer uniquely combines
ultra-relativistic focused intensities of about 1020 W/cm2 with a pulse duration
of sub-two carrier-wave cycles. The coherent combination of two sequentially
amplified and complementary spectral ranges yields sub-5-fs pulses with multi-TW
peak power. The application of this source allows the generation of a broad
spectral continuum at 100-eV photon energy in gases as well as high-order
harmonics in relativistic plasmas. Unprecedented spatio-temporal confinement of
light now permits the investigation of electric-field-driven electron phenomena
in the relativistic regime and ultimately the rise of next-generation intense
isolated attosecond sources.
PMID- 28701693
TI - Transcription factor Hlx controls a systematic switch from white to brown fat
through Prdm16-mediated co-activation.
AB - Browning of subcutaneous white fat (iWAT) involves several reprograming events,
but the underlying mechanisms are incompletely understood. Here we show that the
transcription factor Hlx is selectively expressed in brown adipose tissue (BAT)
and iWAT, and is translationally upregulated by beta3-adrenergic signaling
mediated suppression of the translational inhibitor 4E-BP1. Hlx interacts with
and is co-activated by Prdm16 to control BAT-selective gene expression and
mitochondrial biogenesis. Hlx heterozygous knockout mice have defects in brown
like adipocyte formation in iWAT, and develop glucose intolerance and high fat
induced hepatic steatosis. Conversely, transgenic expression of Hlx at a
physiological level drives a full program of thermogenesis and converts iWAT to
brown-like fat, which improves glucose homeostasis and prevents obesity and
hepatic steatosis. The adipose remodeling phenotypes are recapitulated by fat
specific injection of Hlx knockdown and overexpression viruses, respectively. Our
studies establish Hlx as a powerful regulator for systematic white adipose tissue
browning and offer molecular insights into the underlying transcriptional
mechanism.The transcriptional co-activator Prdm16 regulates browning of white
adipose tissue (WAT). Here, the authors show that Prdm16 interacts with the
transcription factor Hlx, which is stabilized in response to beta3-adrenergic
signaling, to increase thermogenic gene expression and mitochondrial biogenesis
in subcutaneous WAT.
PMID- 28701694
TI - Defective CFTR leads to aberrant beta-catenin activation and kidney fibrosis.
AB - Cystic fibrosis transmembrane conductance regulator (CFTR), known as a cAMP
activated Cl- channel, is widely expressed at the apical membrane of epithelial
cells in a wide variety of tissues. Of note, despite the abundant expression of
CFTR in mammalian kidney, the role of CFTR in kidney disease development is
unclear. Here, we report that CFTR expression is downregulated in the UUO
(unilateral ureteral obstruction)-induced kidney fibrosis mouse model and human
fibrotic kidneys. Dysfunction or downregulation of CFTR in renal epithelial cells
leads to alteration of genes involved in Epithelial-Mesenchymal Transition (EMT)
and kidney fibrosis. In addition, dysregulation of CFTR activates canonical
Wnt/beta-catenin signaling pathways, whereas the beta-catenin inhibitor reverses
the effects of CFTR downregulation on EMT marker. More interestingly, CFTR
interacts with Dishevelled 2 (Dvl2), a key component of Wnt signaling, thereby
suppressing the activation of beta-catenin. Compared to wild type, deltaF508 mice
with UUO treatment exhibit significantly higher beta-catenin activity with
aggregated kidney fibrogenesis, which is reduced by forced overexpression of
CFTR. Taken together, our study reveals a novel mechanism by which CFTR regulates
Wnt/beta-catenin signaling pertinent to progression of kidney fibrosis and
indicates a potential treatment target.
PMID- 28701695
TI - Optimized analysis of blood flow and wall shear stress in the common carotid
artery of rat model by phase-contrast MRI.
AB - The present study systemically investigated the influence of gated/non-gated
sequences, velocity encoding (VENC), and spatial resolution on blood flow, wall
shear stress (WSS), and artery area evaluations when scanning the common carotid
artery (CCA) in rats using phase-contrast magnetic resonance imaging (PC-MRI). We
first tested whether or not non-gated PC-MRI was appropriate for evaluating blood
flow and WSS in rats. For both gated and non-gated techniques, VENC values in the
range of 60-120 cm/s with an interval of 10 cm/s were also tested. Second, we
optimized the in-plane resolution of PC-MRI for blood flow and WSS measurements.
Results showed the usage of a gated instrument can provide more reproducible
assessments, whereas VENC had an insignificant influence on all hemodynamic
measurements (all P > 0.05). Lower resolutions, such as 0.63 mm, led to
significant overestimations in blood flow and artery area quantifications and to
an underestimation in WSS measurements (all P < 0.05). However, a higher
resolution of 0.16 mm slightly increased measurement variation. As a tradeoff
between accuracy and scan time, we propose a gated PC-MRI sequence with a VENC of
120 cm/s and a resolution of 0.21 mm to be used to extract hemodynamic
information about rat CCA.
PMID- 28701696
TI - Numerical Simulations of Directed Self-Assembly in Diblock Copolymer Films using
Zone Annealing and Pattern Templating.
AB - Bulk fabrication of surface patterns with sub-20 nm feature sizes is immensely
desirable for many existing and emerging technologies. Directed self-assembly
(DSA) of block copolymers (BCPs) has been a recently demonstrated approach to
achieve such feature resolution over large-scale areas with minimal defect
populations. However, much work remains to understand and optimize DSA methods in
order to move this field forward. This paper presents large-scale numerical
simulations of zone annealing and chemo-epitaxy processing of BCP films to
achieve long-range orientational order. The simulations utilize a Time-Dependent
Ginzburg-Landau model and parallel processing to elucidate relationships between
the magnitude and velocity of a moving thermal gradient and the resulting BCP
domain orientations and defect densities. Additional simulations have been
conducted to study to what degree orientational order can be further improved by
combining zone annealing and chemo-epitaxy techniques. It is found that these two
DSA methods do synergistically enhance long-range order with a particular
relationship between thermal gradient velocity and chemical template spacing.
PMID- 28701697
TI - Peptidomics of an in vitro digested alpha-Gal carrying protein revealed IgE
reactive peptides.
AB - The mammalian carbohydrate galactose-alpha1,3-galactose (alpha-Gal) causes a
novel form of food allergy, red meat allergy, where patients experience severe
allergic reactions several hours after red meat consumption. Here we explored
gastric digestion of alpha-Gal glycoproteins using an in vitro model. Bovine
thyroglobulin (BTG), a typical alpha-Gal carrying glycoprotein, was digested with
pepsin. The resulting peptides were characterised by SDS PAGE, immunoblot and
ImmunoCAP using sera from 20 red meat allergic patients. During pepsinolysis of
BTG, a wide range of peptide bands was observed of which 14 to 17 kDa peptides
remained stable throughout the gastric phase. The presence of the alpha-Gal
epitope on the obtained peptides was demonstrated by an anti-alpha-Gal antibody
and IgE from red meat allergic patients. The alpha-Gal digests were able to
inhibit up to 86% of IgE reactivity to BTG. Importantly, basophil activation test
demonstrated that the allergenic activity of BTG was retained after digestion in
all four tested patients. Mass spectrometry-based peptidomics revealed that these
peptides represent mostly internal and C-terminal parts of the protein, where the
most potent IgE-binding alpha-Gal residues were identified at Asn1756, Asn1850
and Asn2231. Thus allergenic alpha-Gal epitopes are stable to pepsinolysis,
reinforcing their role as clinically relevant food allergens.
PMID- 28701698
TI - Global Mapping of the Macrophage-HIV-1 Transcriptome Reveals that Productive
Infection Induces Remodeling of Host Cell DNA and Chromatin.
AB - It has been proposed that macrophages could serve as long-lived compartments for
HIV-1 infection under in vivo situations because these cells are resistant to the
virus-mediated cytopathic effect, produce progeny virus over extended periods of
time and are localized in tissues that are often less accessible by treatment.
Comprehensive experimental studies are thus needed to characterize the HIV-1
induced modulation of host genes in these myeloid lineage cells. To shed light on
this important issue, we performed comparative analyses of mRNA expression levels
of host genes in uninfected bystander and HIV-1-infected human macrophages using
an infectious reporter virus construct coupled with a large-scale RNA sequencing
approach. We observed a rapid differential expression of several host factors in
the productively infected macrophage population including genes regulating DNA
replication factors and chromatin remodeling. A siRNA-mediated screening study to
functionally identify host determinants involved in HIV-1 biology has provided
new information on the virus molecular regulation in macrophages.
PMID- 28701699
TI - Dynamics of snap-off and pore-filling events during two-phase fluid flow in
permeable media.
AB - Understanding the pore-scale dynamics of two-phase fluid flow in permeable media
is important in many processes such as water infiltration in soils, oil recovery,
and geo-sequestration of CO2. The two most important processes that compete
during the displacement of a non-wetting fluid by a wetting fluid are pore
filling or piston-like displacement and snap-off; this latter process can lead to
trapping of the non-wetting phase. We present a three-dimensional dynamic
visualization study using fast synchrotron X-ray micro-tomography to provide new
insights into these processes by conducting a time-resolved pore-by-pore analysis
of the local curvature and capillary pressure. We show that the time-scales of
interface movement and brine layer swelling leading to snap-off are several
minutes, orders of magnitude slower than observed for Haines jumps in drainage.
The local capillary pressure increases rapidly after snap-off as the trapped
phase finds a position that is a new local energy minimum. However, the pressure
change is less dramatic than that observed during drainage. We also show that the
brine-oil interface jumps from pore-to-pore during imbibition at an approximately
constant local capillary pressure, with an event size of the order of an average
pore size, again much smaller than the large bursts seen during drainage.
PMID- 28701700
TI - HDNetDB: A Molecular Interaction Database for Network-Oriented Investigations
into Huntington's Disease.
AB - Huntington's disease (HD) is a progressive and fatal neurodegenerative disorder
caused by an expanded CAG repeat in the huntingtin gene. Although HD is
monogenic, its molecular manifestation appears highly complex and involves
multiple cellular processes. The recent application of high throughput platforms
such as microarrays and mass-spectrometry has indicated multiple pathogenic
routes. The massive data generated by these techniques together with the
complexity of the pathogenesis, however, pose considerable challenges to
researchers. Network-based methods can provide valuable tools to consolidate
newly generated data with existing knowledge, and to decipher the interwoven
molecular mechanisms underlying HD. To facilitate research on HD in a network
oriented manner, we have developed HDNetDB, a database that integrates molecular
interactions with many HD-relevant datasets. It allows users to obtain, visualize
and prioritize molecular interaction networks using HD-relevant gene expression,
phenotypic and other types of data obtained from human samples or model
organisms. We illustrated several HDNetDB functionalities through a case study
and identified proteins that constitute potential cross-talk between HD and the
unfolded protein response (UPR). HDNetDB is publicly accessible at
http://hdnetdb.sysbiolab.eu .
PMID- 28701701
TI - Systematic discovery of genetic modulation by Jumonji histone demethylases in
Drosophila.
AB - Jumonji (JmjC) domain proteins influence gene expression and chromatin
organization by way of histone demethylation, which provides a means to regulate
the activity of genes across the genome. JmjC proteins have been associated with
many human diseases including various cancers, developmental and neurological
disorders, however, the shared biology and possible common contribution to
organismal development and tissue homeostasis of all JmjC proteins remains
unclear. Here, we systematically tested the function of all 13 Drosophila JmjC
genes. Generation of molecularly defined null mutants revealed that loss of 8 out
of 13 JmjC genes modify position effect variegation (PEV) phenotypes, consistent
with their ascribed role in regulating chromatin organization. However, most JmjC
genes do not critically regulate development, as 10 members are viable and
fertile with no obvious developmental defects. Rather, we find that different
JmjC mutants specifically alter the phenotypic outcomes in various sensitized
genetic backgrounds. Our data demonstrate that, rather than controlling essential
gene expression programs, Drosophila JmjC proteins generally act to "fine-tune"
different biological processes.
PMID- 28701702
TI - The influence of postharvest UV-C treatment on anthocyanin biosynthesis in fresh
cut red cabbage.
AB - Red cabbage (Brassica oleracea L. var. capitata f. rubra DC.) is a fresh edible
vegetable consumed globally that contains high levels of antioxidant compounds
including anthocyanins. In this study, fresh-cut red cabbage was treated with
different Ultraviolet-C (UV-C) dosages. Fifteen cyanidin derivatives were
observed in UV-C treated fresh-cut red cabbage; four of these were anthocyanins
absent in control samples. The optimum dose of UV-C for enhancing total
anthocyanin content in fresh-cut red cabbage was 3.0 kJ/m2. Different UV-C
irradiation doses resulted in miscellaneous responses for each of the anthocyanin
compounds, and these alterations appeared to be dose-dependent. The expression of
genes relating to anthocyanin metabolism was altered by UV-C irradiation. For
example, genes for biosynthetic enzymes including glycosyltransferase and
acyltransferase, as well as R2R3 MYB transcription factors (production of
anthocyanin pigment 1 and MYB114), had strongly increased expression following UV
C treatment. These results are in accord with the roles of these gene products in
anthocyanin metabolism. This is, to the authors' knowledge, the first report
demonstrating that UV-C treatment can increase the antioxidant activity in fresh
cut red cabbage in storage. Moreover, our detailed phytochemical and gene
expression analysis establish specific roles for both anthocyanins and metabolism
genes in this process.
PMID- 28701703
TI - The behavioral and neural basis of empathic blame.
AB - Mature moral judgments rely both on a perpetrator's intent to cause harm, and
also on the actual harm caused-even when unintended. Much prior research asks how
intent information is represented neurally, but little asks how even unintended
harms influence judgment. We interrogate the psychological and neural basis of
this process, focusing especially on the role of empathy for the victim of a
harmful act. Using fMRI, we found that the 'empathy for pain' network was
involved in encoding harmful outcomes and integrating harmfulness information for
different types of moral judgments, and individual differences in the extent to
which this network was active during encoding and integration of harmfulness
information determined severity of moral judgments. Additionally, activity in the
network was down-regulated for acceptability, but not blame, judgments for
accidental harm condition, suggesting that these two types of moral evaluations
are neurobiologically dissociable. These results support a model of "empathic
blame", whereby the perceived suffering of a victim colors moral judgment of an
accidental harmdoer.
PMID- 28701704
TI - ConcatSeq: A method for increasing throughput of single molecule sequencing by
concatenating short DNA fragments.
AB - Single molecule sequencing (SMS) platforms enable base sequences to be read
directly from individual strands of DNA in real-time. Though capable of long read
lengths, SMS platforms currently suffer from low throughput compared to competing
short-read sequencing technologies. Here, we present a novel strategy for
sequencing library preparation, dubbed ConcatSeq, which increases the throughput
of SMS platforms by generating long concatenated templates from pools of short
DNA molecules. We demonstrate adaptation of this technique to two target
enrichment workflows, commonly used for oncology applications, and feasibility
using PacBio single molecule real-time (SMRT) technology. Our approach is capable
of increasing the sequencing throughput of the PacBio RSII platform by more than
five-fold, while maintaining the ability to correctly call allele frequencies of
known single nucleotide variants. ConcatSeq provides a versatile new sample
preparation tool for long-read sequencing technologies.
PMID- 28701705
TI - Development of sodium acetate trihydrate-ethylene glycol composite phase change
materials with enhanced thermophysical properties for thermal comfort and
therapeutic applications.
AB - The heat packs using phase change materials (PCMs) are designed for possible
applications such as body comfort and medical applications under adverse
situations. The development and performance of such heat packs rely on
thermophysical properties of PCMs such as latent heat, suitable heat releasing
temperature, degree of supercooling, effective heat releasing time, crystallite
size, stability against spontaneous nucleation in metastable supercooled liquid
state and thermal stability during heating and cooling cycles. Such PCMs are rare
and the available PCMs do not exhibit such properties simultaneously to meet the
desired requirements. The present work reports a facile approach for the design
and development of ethylene glycol (EG) and aqueous sodium acetate trihydrate
(SAT) based composite phase change materials, showing these properties
simultaneously. The addition of 2-3 wt% EG in aqueous SAT enhances the softness
of SAT crystallites, its degree of supercooling and most importantly the
effective heat releasing time by ~10% with respect to aqueous SAT material. In
addition, the maximum heat releasing temperature of aqueous SAT has been tailored
from 56.5 degrees C to 55 degrees C, 54.9 degrees C, 53.5 degrees C, 51.8
degrees C and 43.2 degrees C using 2%, 3%, 5%, 7% and 10 wt% EG respectively,
making the aqueous SAT-EG composite PCMs suitable for desired thermal
applications.
PMID- 28701706
TI - Intraoperative frozen section can be reduced in thyroid nodules classified as
Bethesda categories V and VI.
AB - Intraoperative frozen section (FS) can be reduced during thyroid lobectomy
according to the results of fine needle aspiration (FNA). We evaluated the role
of intraoperative FS in thyroid nodules with different diagnostic categories of
the Bethesda System for Reporting Thyroid Cytopathology by FNA. This
retrospective study included 1,235 nodules collected via thyroidectomy with both
preoperative FNA and intraoperative FS at the Second Affiliated Hospital of
Zhejiang University School of Medicine, from January 2011 to January 2014. FNA
cytological diagnosis was classified into six categories, based on the Bethesda
system. The diagnostic findings of FNA cytology and FS histology were compared
with the final histological results. 189 nodules were benign. The remainder were
malignant. FS diagnosis was more accurate than FNA diagnosis for nodules
classified as Bethesda Categories II, III, and IV (P < 0.05). However, the
accuracy of FNA diagnosis in nodules assigned Bethesda Categories V and VI was
significantly higher than that of FS (P < 0.05). FS appears be beneficial for
thyroid nodules classified as Bethesda categories I through IV. FS may not be
necessary in nodules diagnosed as Bethesda Categories V and VI.
PMID- 28701707
TI - Anti-cancerous effect of albumin coated silver nanoparticles on MDA-MB 231 human
breast cancer cell line.
AB - With the aim of making specific targeting of silver nanoparticles as a drug for
tumor cells and developing new anticancer agents, a novel nano-composite was
developed. Albumin coated silver nanoparticles (ASNPs) were synthesized, and
their anti-cancerous effects were evaluated against MDA-MB 231, a human breast
cancer cell line. The synthesized ASNPs were characterized by spectroscopic
methods. The morphological changes of the cells were observed by inverted,
florescent microscopy and also by DNA ladder pattern on gel electrophoresis; the
results revealed that the cell death process occurred through the apoptosis
mechanism. It was found that ASNPs with a size of 90 nm and negatively charged
with a zeta-potential of about -20 mV could be specifically taken up by tumor
cells. The LD50 of ASNPs against MDA-MB 231 (5 MUM), was found to be 30 times
higher than that for white normal blood cells (152 MUM). The characteristics of
the synthesized ASNPs included; intact structure of coated albumin, higher
cytotoxicity against cancer cells than over normal cells, and cell death based on
apoptosis and reduction of gland tumor sizes in mice. This work indicates that
ASNPs could be a good candidate for chemotherapeutic drug.
PMID- 28701708
TI - Beyond the Debye length in high ionic strength solution: direct protein detection
with field-effect transistors (FETs) in human serum.
AB - In this study, a new type of field-effect transistor (FET)-based biosensor is
demonstrated to be able to overcome the problem of severe charge-screening effect
caused by high ionic strength in solution and detect proteins in physiological
environment. Antibody or aptamer-immobilized AlGaN/GaN high electron mobility
transistors (HEMTs) are used to directly detect proteins, including HIV-1 RT,
CEA, NT-proBNP and CRP, in 1X PBS (with 1%BSA) or human sera. The samples do not
need any dilution or washing process to reduce the ionic strength. The sensor
shows high sensitivity and the detection takes only 5 minutes. The designs of the
sensor, the methodology of the measurement, and the working mechanism of the
sensor are discussed and investigated. A theoretical model is proposed based on
the finding of the experiments. This sensor is promising for point-of-care, home
healthcare, and mobile diagnostic device.
PMID- 28701709
TI - PSMA expression by microvasculature of thyroid tumors - Potential implications
for PSMA theranostics.
AB - Prostate-specific membrane antigen (PSMA) is overexpressed in prostate cancer
epithelium, making it a promising target for molecular imaging and therapy.
Recently, several studies found unexpected PSMA radiotracer uptake by thyroid
tumors, including radioiodine-refractory (RAIR) cancers. PSMA expression was
reported in tumor-associated endothelium of various malignancies, however it has
not been systematically addressed in thyroid tumors. We found that PSMA was
frequently expressed in microvessels of thyroid tumors (120/267), but not in
benign thyroid tissue. PSMA expression in neovasculature was highly irregular
ranging from 19% in benign tumors to over 50% in thyroid cancer. Such
heterogeneity was not directly attributed to endothelial cell proliferation as
confirmed by immunostaining with proliferation-associated endothelial marker
CD105. PSMA expression was associated with tumor size (p = 0.02) and vascular
invasion in follicular carcinoma (p = 0.03), but not with other baseline
histological, and clinical parameters. Significant translational implication is
that RAIR tumors and high-grade cancers maintain high level of PSMA expression,
and can be targeted by PSMA ligand radiopharmaceuticals. Our study predicts
several pitfalls potentially associated with PSMA imaging of the thyroid, such as
low expression in oncocytic tumors, absence of organ specificity, and PSMA
positivity in dendritic cells of chronic thyroiditis, which is described for the
first time.
PMID- 28701710
TI - Deficient Vitamin E Uptake During Development Impairs Neural Tube Closure in Mice
Lacking Lipoprotein Receptor SR-BI.
AB - SR-BI is the main receptor for high density lipoproteins (HDL) and mediates the
bidirectional transport of lipids, such as cholesterol and vitamin E, between
these particles and cells. During early development, SR-BI is expressed in
extraembryonic tissue, specifically in trophoblast giant cells in the parietal
yolk sac. We previously showed that approximately 50% of SR-BI-/- embryos fail to
close the anterior neural tube and develop exencephaly, a perinatal lethal
condition. Here, we evaluated the role of SR-BI in embryonic vitamin E uptake
during murine neural tube closure. Our results showed that SR-BI-/- embryos had a
very low vitamin E content in comparison to SR-BI+/+ embryos. Whereas SR-BI-/-
embryos with closed neural tubes (nSR-BI-/-) had high levels of reactive oxygen
species (ROS), intermediate ROS levels between SR-BI+/+ and nSR-BI-/- embryos
were detected in SR-BI-/- with NTD (NTD SR-BI-/-). Reduced expression of Pax3,
Alx1 and Alx3 genes was found in NTD SR-BI-/- embryos. Maternal alpha-tocopherol
dietary supplementation prevented NTD almost completely (from 54% to 2%, p <
0.001) in SR-BI-/- embryos and normalized ROS and gene expression levels. In sum,
our results suggest the involvement of SR-BI in the maternal provision of
embryonic vitamin E to the mouse embryo during neural tube closure.
PMID- 28701711
TI - Amplification mode differs along the length of the mouse cochlea as revealed by
connexin 26 deletion from specific gap junctions.
AB - The sharp frequency tuning and exquisite sensitivity of the mammalian cochlea is
due to active forces delivered by outer hair cells (OHCs) to the cochlear
partition. Force transmission is mediated and modulated by specialized cells,
including Deiters' cells (DCs) and pillar cells (PCs), coupled by gap-junctions
composed of connexin 26 (Cx26) and Cx30. We created a mouse with conditional Cx26
knock-out (Cx26 cKO) in DCs and PCs that did not influence sensory transduction,
receptor-current-driving-voltage, low-mid-frequency distortion-product
otoacoustic-emissions (DPOAEs), and passive basilar membrane (BM) responses.
However, the Cx26 cKO desensitizes mid-high-frequency DPOAEs and active BM
responses and sensitizes low-mid-frequency neural excitation. This functional
segregation may indicate that the flexible, apical turn cochlear partition
facilitates transfer of OHC displacements (isotonic forces) for cochlear
amplification and neural excitation. DC and PC Cx26 expression is essential for
cochlear amplification in the stiff basal turn, possibly through maintaining
cochlear partition mechanical impedance, thereby ensuring effective transfer of
OHC isometric forces.
PMID- 28701712
TI - Use of Single-Frequency Impedance Spectroscopy to Characterize the Growth
Dynamics of Biofilm Formation in Pseudomonas aeruginosa.
AB - Impedance spectroscopy has been applied in prokaryotic and eukaryotic cytometry
as a label-free method for the investigation of adherent cells. In this paper,
its use for characterizing the growth dynamics of P. aeruginosa biofilms is
described and compared to crystal violet staining and confocal microscopy. The
method allows monitoring the growth of biofilm-forming P. aeruginosa in a
continuous and label-free manner over a period of 72 h in a 96 well plate format.
Impedance curves obtained for P. aeruginosa PA14 wild type and mutant strains
with a transposon insertion in pqsA and pelA genes exhibited distinct phases. We
propose that the slope of the declining curve following a maximum at ca. 35-40 h
is a measure of biofilm formation. Transplant experiments with P. aeruginosa
biofilms and paraffin suggest that the impedance also reflects pellicle formation
at the liquid-air interface, a barely considered contributor to impedance.
Finally, the impairment of biofilm formation upon treatment of cultures with L
arginine and with ciprofloxacin, tobramycin and meropenem was studied by single
frequency impedance spectroscopy. We suggest that these findings qualify
impedance spectroscopy as an additional technique to characterize biofilm
formation and its modulation by small molecule drugs.
PMID- 28701713
TI - An ant-coccid mutualism affects the behavior of the parasitoid Aenasius
bambawalei, but not that of the ghost ant Tetramorium bicarinatum.
AB - Mutualisms between honeydew-producing insects and ants change the emission of
volatiles from plants, but whether such changes alter the behaviors of ants that
tend honeydew-producing insects or wasps that parasitize honeydew-producing
insects remain unknown. This study compared the behavioral responses of the ant
Tetramorium bicarinatum and the parasitoid wasp Aenasius bambawalei to odors from
cotton plants infested with the mealybug Phenacoccus solenopsis or infested with
the mealybug and the ant, which tends the mealybug. The ant could not distinguish
between the volatiles from plants infested with the mealybug alone and those from
plants infested with the mealybug and the ant. Likewise, naive wasps failed to
distinguish between volatiles from the two treatments. In contrast, experienced
wasps preferred volatiles from plants infested with the mealybug and the ant.
Volatile analysis showed that the amounts of MeSA were increased and those of
methyl nicotinate were decreased when plants were infested by the mealybug and
the ant rather than when plants were uninfested or were infested by the mealybug
alone. Thus, the mutualism between the mealybug and ant changed the volatiles
emitted by cotton plants such that the attraction of A. bambawalei (but not that
of the ant) to the plants was increased.
PMID- 28701714
TI - Structural and Biochemical Characterization of Apicomplexan Inorganic
Pyrophosphatases.
AB - Inorganic pyrophosphatases (PPase) participate in energy cycling and they are
essential for growth and survival of organisms. Here we report extensive
structural and functional characterization of soluble PPases from the human
parasites Plasmodium falciparum (PfPPase) and Toxoplasma gondii (TgPPase). Our
results show that PfPPase is a cytosolic enzyme whose gene expression is
upregulated during parasite asexual stages. Cambialistic PfPPase actively
hydrolyzes linear short chain polyphosphates like PPi, polyP3 and ATP in the
presence of Zn2+. A remarkable new feature of PfPPase is the low complexity
asparagine-rich N-terminal region that mediates its dimerization. Deletion of N
region has an unexpected and substantial effect on the stability of PfPPase
domain, resulting in aggregation and significant loss of enzyme activity.
Significantly, the crystal structures of PfPPase and TgPPase reveal unusual and
unprecedented dimeric organizations and provide new fundamental insights into the
variety of oligomeric assemblies possible in eukaryotic inorganic PPases.
PMID- 28701715
TI - Clinical relevance of reduced decorrelation signals in the diabetic inner choroid
on optical coherence tomography angiography.
AB - Diabetes induces lesions of the retinal and choroidal capillaries, which promote
the pathogenesis of diabetic retinopathy (DR). The decorrelation signals in
optical coherence tomography angiography (OCTA) represent the blood flow and
vascular structure, and three-dimensional OCTA images enable individual capillary
layers to be evaluated separately. The current study documented that en-face OCTA
images revealed spots of flow void in the choriocapillaris layer in eyes with DR.
Quantitative investigation demonstrated that non-flow areas within the central
subfield (CSF) increased in eyes with more severe DR grades. The non-flow areas
in the choriocapillaris layer were also associated with poorer visual acuity (VA)
in all 108 eyes. A modest correlation was noted between the areas of flow void
and poorer VA in 69 eyes without DME, whereas the non-flow areas were not related
to VA or to CSF thickness measured by OCT in 39 eyes with DME. In 12 eyes with
ischemic maculopathy, the choriocapillaris layer beneath the disrupted ellipsoid
zone of the photoreceptor (EZ) had greater areas of flow void than did the area
beneath an intact EZ. These data suggested that disrupted choroidal circulation
has clinical relevance and contributes to the pathogenesis of DR.
PMID- 28701716
TI - GLYAT regulates JNK-mediated cell death in Drosophila.
AB - Cell death is a fundamental progress that regulates cell number, tissue
homeostasis and organ size in development. The c-Jun N-terminal kinase (JNK)
pathway has been evolutionarily conserved from fly to human, and plays essential
roles in regulating cell death. To characterize additional genes that regulate
JNK signaling, we performed a genetic screen in Drosophila and identified dGLYAT,
a novel gene whose function was previously unknown, as a modulator of JNK
mediated cell death. We found that loss of dGLYAT suppressed JNK activation and
cell death triggered by over-expression of Egr or Hep, or depletion of puc or lgl
in development, suggesting dGLYAT regulates both ectopic and physiological
functions of JNK pathway. Furthermore, we showed that loss of dGLYAT inhibits JNK
mediated ROS production, suggesting dGLYAT regulates multiple functions of JNK
signaling in vivo.
PMID- 28701717
TI - Tunable graphene-based hybrid plasmonic modulators for subwavelength confinement.
AB - Electro-optical modulators which work at the near-infrared range are significant
for a variety of applications such as communication and sensing. However,
currently available approaches result in rather bulky devices which suffer from
low integration and can hardly operate at low power consumption levels. Graphene,
an emerging advanced material, has been widely utilized due to its tunability by
gating which allows one to realize active optical devices. Plasmonic waveguides,
one of the most promising candidates for subwavelength optical confinement,
provide a way to manipulate light on scales much smaller than the wavelength. In
this paper, we combine the advantages of graphene and plasmonic waveguides and
propose a tunable graphene-based hybrid plasmonic modulator (GHPM). Considering
several parameters of the GHPM, the modulation depth can reach approximately 0.3
dB.MUm-1 at low gating voltages. Moreover, we combine GHPM with metal-insulator
metal (MIM) structure to propose another symmetrical GHPM with a modulation depth
of 0.6 dB.MUm-1. Our modulators which utilize the light-matter interaction tuned
by electro-doped graphene are of great potential for many applications in
nanophotonics.
PMID- 28701718
TI - Recycling and Self-Healing of Polybenzoxazines with Dynamic Sulfide Linkages.
AB - In this work, a recycling and self-healing strategy for polybenzoxazines through
both S-S bond cleavage-reformation reaction and supramolecular attractions is
described. Both recyclable and self-healable polybenzoxazines can be prepared
from low cost chemicals with a simple procedure in only 30 minutes. For this
purpose, inverse vulcanization of poly(propylene oxide)benzoxazine (PPOB) and
diallybenzoxazine (B-al) with elemental sulfur was performed at 185 degrees C.
The obtained cross-linked polymer films exhibited thermally driven recycling
ability up to 5 cycles. Moreover, the self-healing ability of a test specimen was
shown. Spectral characterizations, thermal stability and fracture toughness of
the films were investigated after each recycling.
PMID- 28701720
TI - Physiological demands of a swimming-based video game: Influence of gender,
swimming background, and exergame experience.
AB - Active video games (exergames) may provide short-term increase in energy
expenditure. We explored the effects of gender and prior experience on aerobic
and anaerobic energy systems contributions, and the activity profiles of 40
participants playing with a swimming exergame. We recorded oxygen consumption and
assessed blood lactate after each swimming technique. We also filmed
participants' gameplays, divided them into different phases and tagged them as
active or inactive. Anaerobic pathway accounted for 8.9 +/- 5.6% of total energy
expenditure and although experienced players were less active compared to novice
counterparts (eta2 < 0.15, p < 0.05), physiological measures were not different
between performing groups. However, players with real-swimming experience during
the first technique had higher heart rate (partial-eta2 = 0.09, p < 0.05). Our
results suggest that short-term increase in physiological measures might happen
in the beginning of gameplay because of unfamiliarity with the game mechanics.
Despite low levels of activity compared to real sport, both aerobic and anaerobic
energy systems should be considered in the evaluation of exergames. Game
mechanics (involving the whole body) and strategies to minimize pragmatic play
might be used for effective and meaningful game experience.
PMID- 28701719
TI - Dynamic gene expression response to altered gravity in human T cells.
AB - We investigated the dynamics of immediate and initial gene expression response to
different gravitational environments in human Jurkat T lymphocytic cells and
compared expression profiles to identify potential gravity-regulated genes and
adaptation processes. We used the Affymetrix GeneChip(r) Human Transcriptome
Array 2.0 containing 44,699 protein coding genes and 22,829 non-protein coding
genes and performed the experiments during a parabolic flight and a suborbital
ballistic rocket mission to cross-validate gravity-regulated gene expression
through independent research platforms and different sets of control experiments
to exclude other factors than alteration of gravity. We found that gene
expression in human T cells rapidly responded to altered gravity in the time
frame of 20 s and 5 min. The initial response to microgravity involved mostly
regulatory RNAs. We identified three gravity-regulated genes which could be cross
validated in both completely independent experiment missions: ATP6V1A/D, a
vacuolar H + -ATPase (V-ATPase) responsible for acidification during bone
resorption, IGHD3-3/IGHD3-10, diversity genes of the immunoglobulin heavy-chain
locus participating in V(D)J recombination, and LINC00837, a long intergenic non
protein coding RNA. Due to the extensive and rapid alteration of gene expression
associated with regulatory RNAs, we conclude that human cells are equipped with a
robust and efficient adaptation potential when challenged with altered
gravitational environments.
PMID- 28701721
TI - TSG-6 Secreted by Human Adipose Tissue-derived Mesenchymal Stem Cells Ameliorates
DSS-induced colitis by Inducing M2 Macrophage Polarization in Mice.
AB - Previous studies have revealed that mesenchymal stem cells (MSCs) alleviate
inflammatory bowel disease (IBD) by modulating inflammatory cytokines in the
inflamed intestine. However, the mechanisms underlying these effects are not
completely understood. We sought to investigate the therapeutic effects of human
adipose tissue-derived (hAT)-MSCs in an IBD mouse model and to explore the
mechanisms of the regulation of inflammation. Dextran sulfate sodium-induced
colitis mice were infused with hAT-MSCs intraperitoneally and colon tissues were
collected on day 10. hAT-MSCs were shown to induce the expression of M2
macrophage markers and to regulate the expression of pro- and anti-inflammatory
cytokines in the colon. Quantitative real time-PCR analyses demonstrated that
less than 20 hAT-MSCs, 0.001% of all intraperitoneally injected hAT-MSCs, were
detected in the inflamed colon. To investigate the effects of hAT-MSC-secreted
factors in vitro, transwell co-culture system was used, demonstrating that tumour
necrosis factor-alpha-induced gene/protein 6 (TSG-6) released by hAT-MSCs induces
M2 macrophages. In vivo, hAT-MSCs transfected with TSG-6 small interfering RNA,
administered intraperitoneally, were not able to induce M2 macrophage phenotype
switch in the inflamed colon and had no significant effects on IBD severity. In
conclusion, hAT-MSC-produced TSG-6 can ameliorate IBD by inducing M2 macrophage
switch in mice.
PMID- 28701722
TI - Asxl1 deficiency in embryonic fibroblasts leads to cellular senescence via
impairment of the AKT-E2F pathway and Ezh2 inactivation.
AB - Although ASXL1 mutations are frequently found in human diseases, including
myeloid leukemia, the cell proliferation-associated function of ASXL1 is largely
unknown. Here, we explored the molecular mechanism underlying the growth defect
found in Asxl1-deficient mouse embryonic fibroblasts (MEFs). We found that Asxl1,
through amino acids 371 to 655, interacts with the kinase domain of AKT1. In
Asxl1-null MEFs, IGF-1 was unable to induce AKT1 phosphorylation and activation;
p27Kip1, which forms a ternary complex with ASXL1 and AKT1, therefore remained
unphosphorylated. Hypophosphorylated p27Kip1 is able to enter the nucleus, where
it prevents the phosphorylation of Rb; this ultimately leads to the down
regulation of E2F target genes as confirmed by microarray analysis. We also found
that senescence-associated (SA) genes were upregulated and that SA beta-gal
staining was increased in Asxl1 -/- MEFs. Further, the treatment of an AKT
inhibitor not only stimulated nuclear accumulation of p27Kip1 leading to E2F
inactivation, but also promoted senescence. Finally, Asxl1 disruption augmented
the expression of p16Ink4a as result of the defect in Asxl1-Ezh2 cooperation.
Overall, our study provides the first evidence that Asxl1 both activates the AKT
E2F pathway and cooperates with Ezh2 through direct interactions at early
embryonic stages, reflecting that Asxl1 disruption causes cellular senescence.
PMID- 28701723
TI - The lncRNA MALAT1 acts as a competing endogenous RNA to regulate KRAS expression
by sponging miR-217 in pancreatic ductal adenocarcinoma.
AB - The long noncoding RNA (lncRNA) metastasis-associated lung adenocarcinoma
transcript-1 (MALAT1) has been shown to play an important role in tumourigenesis.
The aim of this study was to investigate the role of MALAT1 in pancreatic ductal
adenocarcinoma. MALAT1 is expressed at higher levels in pancreatic ductal
adenocarcinoma (PDAC) tissues than in nontumour tissues and in metastatic PDAC
than in localized tumours. Patients with PDAC and high MALAT1 expression levels
have shorter overall survival than patients with PDAC and low MALAT1 expression
levels. Knocking down MALAT1 reduces pancreatic tumour cell growth and
proliferation both in vitro and in vivo. Moreover, MALAT1 knockdown inhibits cell
cycle progression and impairs tumour cell migration and invasion. We found that
miR-217 can bind MALAT1 and regulate its expression in PDAC cell lines. We also
found MALAT1 knockdown attenuates the protein expression of KRAS, a known target
of miR-217. After MALAT1 knockdown, KRAS protein expression levels can be rescued
through inhibition of miR-217 expression. More importantly, MALAT1 knockdown does
not directly affect cellular miR-217 expression but decreases the miR-217
nucleus/cytoplasm ratio, suggesting that MALAT1 inhibits the translocation of miR
217 from the nucleus to the cytoplasm.
PMID- 28701724
TI - Dynamic microtubule association of Doublecortin X (DCX) is regulated by its C
terminus.
AB - Doublecortin X (DCX), known to be essential for neuronal migration and cortical
layering in the developing brain, is a 40 kDa microtubule (MT)-associated
protein. DCX directly interacts with MTs via its two structured doublecortin (DC)
domains, but the dynamics of this association and the possible regulatory roles
played by the flanking unstructured regions remain poorly defined. Here, we
employ quantitative fluorescence recovery after photobleaching (FRAP) protocols
in living cells to reveal that DCX shows remarkably rapid and complete exchange
within the MT network but that the removal of the C-terminal region significantly
slows this exchange. We further probed how MT organization or external stimuli
could additionally modulate DCX exchange dynamics. MT depolymerisation
(nocodazole treatment) or stabilization (taxol treatment) further enhanced DCX
exchange rates, however the exchange rates for the C-terminal truncated DCX
protein were resistant to the impact of taxol-induced stabilization. Furthermore,
in response to a hyperosmotic stress stimulus, DCX exchange dynamics were slowed,
and again the C-terminal truncated DCX protein was resistant to the stimulus.
Thus, the DCX dynamically associates with MTs in living cells and its C-terminal
region plays important roles in the MT-DCX association.
PMID- 28701725
TI - Prospective Study on Association of Prostatic Calcifications with Clinical
Symptoms and Results of Treatment in Men with type III prostatitis.
AB - The purpose is to investigate the clinical significance of prostatic calculi in
patients with chronic prostatitis and to discuss the possible treatment.The data
from 277 young males with CP/CPPS were analyzed prospectively. Symptom severity
was measured using the National Institutes of Health Chronic Prostatitis Symptom
Index (NIH-CPSI) and the International Prostatic Symptoms Score (IPSS). Sexual
function was assessed by the International Index of Erectile Function (IIEF-5)
questionnaire. After four weeks of therapy, the NIH-CPSI, IPSS, and IIEF-5 tests
were repeated. The variables were compared between patients with and without
prostatic calcifications using the Students t-test or chi-square test. No
significant differences were found between CP/CPPS patients with and without
prostatic calcifications regarding age, body mass index, prostate volume, CPSI,
IPSS and IIEF-5. Men with calcifications endured symptoms significantly longer
(37.9 +/- 25.2 versus 19.0 +/- 16.4 months, P < 0.01), and had significantly
higher white blood cell counts per high power field in expressed prostatic
secretions (7.7 +/- 12.8 versus 3.9 +/- 4.7; P < 0.01), than patients without
prostatic calcifications, who responded better to medication compared with
patients with prostatic calcifications. In conclusion, patients with
calcifications were more likely to have category IIIA disease and they required a
longer medication period.
PMID- 28701726
TI - Genotype by random environmental interactions gives an advantage to non-favored
minor alleles.
AB - Fixation probability, the probability that the frequency of a newly arising
mutation in a population will eventually reach unity, is a fundamental quantity
in evolutionary genetics. Here we use a number of models (several versions of the
Moran model and the haploid Wright-Fisher model) to examine fixation
probabilities for a constant size population where the fitness is a random
function of both allelic state and spatial position, despite neither allele being
favored on average. The concept of fitness varying with respect to both genotype
and environment is important in models of cancer initiation and progression,
bacterial dynamics, and drug resistance. Under our model spatial heterogeneity
redefines the notion of neutrality for a newly arising mutation, as such
mutations fix at a higher rate than that predicted under neutrality. The
increased fixation probability appears to be due to rare alleles having an
advantage. The magnitude of this effect can be large, and is an increasing
function of the spatial variance and skew in fitness. The effect is largest when
the fitness values of the mutants and wild types are anti-correlated across
environments. We discuss results for both a spatial ring geometry of cells (such
as that of a colonic crypt), a 2D lattice and a mass-action (complete graph)
arrangement.
PMID- 28701727
TI - Free immunoglobulin light chain (FLC) promotes murine colitis and colitis
associated colon carcinogenesis by activating the inflammasome.
AB - Numerous studies have demonstrated that free Ig light chain (FLC), a novel
inflammation mediator, participates in many inflammatory diseases by activating
mast cells and extending the survival of neutrophils. However, it remains unclear
whether FLC is involved in colitis and colitis-associated colon carcinogenesis
(CAC). In this study, we found a significant increase in FLC in murine models of
DSS (Dextran Sulfate Sodium Salt)-induced colitis and CAC compared to controls.
Peptide F991, a functional blocker of FLC, significantly attenuated colitis
progression, which included abrogating the development of diarrhea and tumor
burden, elevating survival rate, greatly reducing the infiltration of
inflammatory cells (such as ROS+ active neutrophils), especially reducing
tumorigenesis in CAC. Furthermore, we demonstrated that F991 inhibited the
activation of the inflammasome by reducing the expression of cleaved caspase-1
and the maturation of IL-1beta and IL-18. Altogether, our findings demonstrate
that FLC can promote the pathogenesis of colitis and CAC and may be used as novel
biomarker for the diagnosis of inflammatory bowel disease. Additionally, F991 may
become a potential therapeutic option for colitis or colorectal cancer.
PMID- 28701728
TI - Nitrogen-Mediated Graphene Oxide Enables Highly Efficient Proton Transfer.
AB - Two-dimensional (2D) graphene and graphene oxide (GO) offer great potential as a
new type of cost-efficient proton-exchange membranes (PEM) for electrochemical
devices. However, fundamental issues of proton transfer mechanism via 2D
membranes are unclear and the transfer barrier for perfect graphene are too high
for practical application. Using ab initio molecular dynamic simulations, we
screened the proton transfer barrier for different un-doped and nitrogen doped GO
membranes, and clarified the corresponding transfer mechanisms. More
significantly, we further identify that N-mediated GO can be built into a highly
efficient PEM with a proton transfer rate of seven orders of magnitude higher
than an un-doped case via. a proton relay mechanism between a ketone-like oxygen
and a pyridine-like nitrogen across the vacancy site. The N-doped 2D GO is also
impermeable to small molecules, and hence a highly efficient PEM for practical
applications.
PMID- 28701729
TI - Bias in recent miRBase annotations potentially associated with RNA quality
issues.
AB - Although microRNAs are supposed to be stable in-vivo, degradation processes
potentially blur our knowledge on the small oligonucleotides. We set to quantify
the effect of degradation on microRNAs in mouse to identify causes for distorted
microRNAs patterns. In liver, we found 298, 99 and 8 microRNAs whose expression
significantly correlated to RNA integrity, storage time at room temperature and
storage time at 4 degrees C, respectively. Expression levels of 226 microRNAs
significantly differed between liver samples with high RNA integrity compared to
liver samples with low RNA integrity by more than two-fold. Especially the 157
microRNAs with increased expression in tissue samples with low RNA integrity were
most recently added to miRBase. Testing potentially confounding sources, e.g. in
vitro degraded RNA depleted of small RNAs, we detected signals for 350 microRNAs,
suggesting cross-hybridization of fragmented RNAs. Therefore, we conclude that
especially microRNAs added in the latest miRBase versions might be artefacts due
to RNA degradation. The results facilitate differentiation between degradation
resilient microRNAs, degradation-sensitive microRNAs, and likely erroneously
annotated microRNAs. The latter were largely identified by NGS but not
experimentally validated and can severely bias microRNA biomarker research and
impact the value of microRNAs as diagnostic, prognostic or therapeutic tools.
PMID- 28701731
TI - BLOC-1 deficiency causes alterations in amino acid profile and in phospholipid
and adenosine metabolism in the postnatal mouse hippocampus.
AB - Biogenesis of lysosome-related organelles complex-1 (BLOC-1) is a protein complex
involved in the formation of endosomal tubular structures that mediates the
sorting of protein cargoes to specialised compartments. In this study, we present
insights into the metabolic consequences caused by BLOC-1 deficiency in pallid
mice, which carry a null mutation in the Bloc1s6 gene encoding an essential
component of this complex. The metabolome of the hippocampus of pallid mice was
analysed using an untargeted, liquid chromatography-coupled mass spectrometric
approach. After data pre-treatment, statistical analysis and pathway enrichment,
we have identified 28 metabolites that showed statistically significant changes
between pallid and wild-type control. These metabolites included amino acids,
nucleobase-containing compounds and lysophospholipids. Interestingly, pallid mice
displayed increased hippocampal levels of the neurotransmitters glutamate and N
acetyl-aspartyl-glutamic acid (NAAG) and their precursor glutamine. Expression of
the sodium-coupled neutral amino acid transporter 1 (SNAT1), which transports
glutamine into neurons, was also upregulated. Conversely, levels of the
neurotransmitter precursors phenylalanine and tryptophan were decreased.
Interestingly, many of these changes could be mapped to overlapping metabolic
pathways. The observed metabolic alterations are likely to affect
neurotransmission and neuronal homeostasis and in turn could mediate the memory
and behavioural impairments observed in BLOC-1-deficient mice.
PMID- 28701730
TI - The MLL recombinome of acute leukemias in 2017.
AB - Chromosomal rearrangements of the human MLL/KMT2A gene are associated with
infant, pediatric, adult and therapy-induced acute leukemias. Here we present the
data obtained from 2345 acute leukemia patients. Genomic breakpoints within the
MLL gene and the involved translocation partner genes (TPGs) were determined and
11 novel TPGs were identified. Thus, a total of 135 different MLL rearrangements
have been identified so far, of which 94 TPGs are now characterized at the
molecular level. In all, 35 out of these 94 TPGs occur recurrently, but only 9
specific gene fusions account for more than 90% of all illegitimate
recombinations of the MLL gene. We observed an age-dependent breakpoint shift
with breakpoints localizing within MLL intron 11 associated with acute
lymphoblastic leukemia and younger patients, while breakpoints in MLL intron 9
predominate in AML or older patients. The molecular characterization of MLL
breakpoints suggests different etiologies in the different age groups and allows
the correlation of functional domains of the MLL gene with clinical outcome. This
study provides a comprehensive analysis of the MLL recombinome in acute leukemia
and demonstrates that the establishment of patient-specific chromosomal fusion
sites allows the design of specific PCR primers for minimal residual disease
analyses for all patients.
PMID- 28701732
TI - Alpha Power Predicts Persistence of Bistable Perception.
AB - Perception is strongly affected by the intrinsic state of the brain, which
controls the propensity to either maintain a particular perceptual interpretation
or switch to another. To understand the mechanisms underlying the spontaneous
drive of the brain to explore alternative interpretations of unchanging stimuli,
we repeatedly recorded high-density EEG after normal sleep and after sleep
deprivation while participants observed a Necker cube image and reported the
durations of the alternating representations of their bistable perception. We
found that local alpha power around the parieto-occipital sulcus within the first
second after the emergence of a perceptual representation predicted the fate of
its duration. An experimentally induced increase in alpha power by means of sleep
deprivation increased the average duration of individual representations. Taken
together, these findings show that high alpha power promotes the stability of a
perceptual representation and suppresses switching to the alternative. The
observations support the hypothesis that synchronization of alpha oscillations
across a wide neuronal network promotes the maintenance and stabilization of its
current perceptual representation. Elevated alpha power could also be key to the
poorly understood cognitive deficits, that typically accompany sleep deprivation,
such as the loss of mental flexibility and lapses of responsiveness.
PMID- 28701733
TI - Endosomal NOX2 oxidase exacerbates virus pathogenicity and is a target for
antiviral therapy.
AB - The imminent threat of viral epidemics and pandemics dictates a need for
therapeutic approaches that target viral pathology irrespective of the infecting
strain. Reactive oxygen species are ancient processes that protect plants, fungi
and animals against invading pathogens including bacteria. However, in mammals
reactive oxygen species production paradoxically promotes virus pathogenicity by
mechanisms not yet defined. Here we identify that the primary enzymatic source of
reactive oxygen species, NOX2 oxidase, is activated by single stranded RNA and
DNA viruses in endocytic compartments resulting in endosomal hydrogen peroxide
generation, which suppresses antiviral and humoral signaling networks via
modification of a unique, highly conserved cysteine residue (Cys98) on Toll-like
receptor-7. Accordingly, targeted inhibition of endosomal reactive oxygen species
production abrogates influenza A virus pathogenicity. We conclude that endosomal
reactive oxygen species promote fundamental molecular mechanisms of viral
pathogenicity, and the specific targeting of this pathogenic process with
endosomal-targeted reactive oxygen species inhibitors has implications for the
treatment of viral disease.Production of reactive oxygen species is an ancient
antimicrobial mechanism, but its role in antiviral defense in mammals is unclear.
Here, To et al. show that virus infection activates endosomal NOX2 oxidase and
restricts TLR7 signaling, and that an endosomal NOX2 inhibitor decreases viral
pathogenicity.
PMID- 28701734
TI - Long noncoding RNA expression profile changes associated with dietary energy in
the sheep testis during sexual maturation.
AB - Spermatogenesis can be affected by nutrition, which operates through normal
physiological processes by changing the testicular mass and hormone levels
profoundly. However, little is known regarding how testis development is
regulated by long noncoding RNA (lncRNA). In this study, we investigated the
effects of high-grain (HG) feeding on testis development during sexual maturation
mediated by lncRNA. The HG diet group showed an increase in growth hormone (GH),
insulin-like growth factor-1 (IGF-1) and testosterone (T) levels, and in the
number of sperm in the seminiferous tubules compared with the hay-fed group (p <
0.05). Moreover, we found 59 differentially expressed (DE) lncRNAs and 229 DE
mRNAs in sheep testis between the two groups. qRT-PCR results of 20 randomly
selected DE lncRNAs and mRNAs were also consistent with the RNA-seq data. Through
functional enrichment analysis and lncRNA-mRNA interaction network analysis, we
screened several lncRNAs that may be enriched for male reproduction such as
spermatogenesis, sperm motility, steroid hormones, MAPK and ErbB signaling
pathways. This study provides a first insight into the development of the testis
with HG feeding in sheep and shows that these changes are associated with
alterations in lncRNA expression.
PMID- 28701735
TI - Quantitative proteomics reveal the anti-tumour mechanism of the carbohydrate
recognition domain of Galectin-3 in Hepatocellular carcinoma.
AB - Hepatocellular carcinoma (HCC) is a serious threat to human health. The
carbohydrate recognition domain of Galectin-3 (Gal3C) has been reported to be an
anti-tumour molecule. In this study, we aim to explore effects of Gal3C in HCC
and its possible molecular mechanism with quantitative proteomics approach. We
found that rGal3C stimulation could inhibit cell viability, migration and
invasion of HepG2. After rGal3C stimulating, 190 proteins were differentially
expressed. Eighty up-regulated proteins located mainly in extracellular exosome
and involved in cell adhesion and metabolism, and 110 down-regulated proteins
located in mitochondria and extracellular exosome, and related to processes of
metabolism and oxidation-reduction. Of the differentially expressed proteins,
CLU, NDRG1, CD166, S100A11 and Galectin-1 were carcinoma-related proteins
affected by rGal3C. Potential receptors of rGal3C were explored by an UV cross
linking capture strategy. We showed that rGal3C could induce dephosphorylating of
FAK/SRC. Blocking of the FAK/SRC pathway resulted in down-regulation of NDRG1.
Immunofluorescence suggested that rGal3C could disrupt integrin clustering. Our
study provides valuable insight into the anti-tumour mechanism of rGal3C in HCC
on a proteomics level and is the first to reveal the possible mechanism involving
integrin/FAK/SRC pathway and NDRG1. These results provide useful guidance of
developing new therapies for HCC.
PMID- 28701736
TI - Epibiotic pressure contributes to biofouling invader success.
AB - Reduced competition is a frequent explanation for the success of many introduced
species. In benthic marine biofouling communities, space limitation leads to high
rates of overgrowth competition. Some species can utilise other living organisms
as substrate (epibiosis), proffering a competitive advantage for the epibiont.
Additionally, some species can prevent or reduce epibiotic settlement on their
surfaces and avoid being basibionts. To test whether epibiotic pressure differs
between native and introduced species, we undertook ex situ experiments comparing
bryozoan larval settlement to determine if introduced species demonstrate a
greater propensity to settle as epibionts, and a reduced propensity to be
basibionts, than native species. Here we report that introduced species
opportunistically settle on any space (bare, native, or introduced), whereas
native species exhibit a strong tendency to settle on and near other natives, but
avoid settling on or near introduced basibionts. In addition, larvae of native
species experience greater larval wastage (mortality) than introduced species,
both in the presence and absence of living substrates. Introduced species'
ability to settle on natives as epibionts, and in turn avoid epibiosis as
basibionts, combined with significantly enhanced native larval wastage, provides
a comprehensive suite of competitive advantages contributing to the invasion
success of these biofouling species.
PMID- 28701737
TI - Circulating primitive erythroblasts establish a functional, protein 4.1R
dependent cytoskeletal network prior to enucleating.
AB - Hematopoietic ontogeny is characterized by distinct primitive and definitive
erythroid lineages. Definitive erythroblasts mature and enucleate extravascularly
and form a unique membrane skeleton, composed of spectrin, 4.1R-complex, and
ankyrinR-complex components, to survive the vicissitudes of the adult
circulation. However, little is known about the formation and composition of the
membrane skeleton in primitive erythroblasts, which progressively mature while
circulating in the embryonic bloodstream. We found that primary primitive
erythroblasts express the major membrane skeleton genes present in similarly
staged definitive erythroblasts, suggesting that the composition and formation of
this membrane network is conserved in maturing primitive and definitive
erythroblasts despite their respective intravascular and extravascular locations.
Membrane deformability and stability of primitive erythroblasts, assayed by
microfluidic studies and fluorescence imaged microdeformation, respectively,
significantly increase prior to enucleation. These functional changes coincide
with protein 4.1 R isoform switching and protein 4.1R-null primitive
erythroblasts fail to establish normal membrane stability and deformability. We
conclude that maturing primitive erythroblasts initially navigate the embryonic
vasculature prior to establishing a deformable cytoskeleton, which is ultimately
formed prior to enucleation. Formation of an erythroid-specific, protein 4.1R
dependent membrane skeleton is an important feature not only of definitive, but
also of primitive, erythropoiesis in mammals.
PMID- 28701738
TI - Increased nocturnal blood pressure variability is associated with renal
arteriolar hyalinosis in normotensive patients with IgA nephropathy.
AB - Abnormal blood pressure (BP) variability (BPV), occurring as beat-to-beat, 24 h,
and day-to-day fluctuations, is related to target organ damage. However, the
associations between abnormal BPV and renal structural changes have not been
clearly investigated. We evaluated the day time and night time BP s.d. and
average real variability (ARV), which reflected short-term BPV, the night time to
day time (N/D) ratio of systolic BP (SBP), and the 7-day BPV, in 29 normotensive
IgA nephropathy (IgAN) patients. We further compared the results with renal
structural changes. The degree of arteriosclerosis was positively correlated with
age, s.d. of night time SBP and the N/D ratio of SBP, and was negatively
correlated with the estimated glomerular filtration rate (eGFR). The degree of
arteriolar hyalinosis was positively correlated with age, night time SBP, s.d. of
day time and night time SBP, day time and night time ARV, the N/D ratio of SBP
and 7-day SBP, and was negatively correlated with the eGFR. A multiple linear
regression analysis revealed that the level of arteriolar hyalinosis, but not
arteriosclerosis, was associated with the s.d. of night time SBP (beta=0.63,
P<0.01) or night time ARV (beta=0.61, P<0.01) after adjustment for age, sex, body
mass index, the eGFR and night time SBP. Multiple linear regression analyses
indicated no significant correlation between the degree of arteriolar hyalinosis
and the N/D ratio of SBP or 7-day SBP s.d. or between the degree of
arteriosclerosis and any of the BPV parameters. In conclusion, short-term night
time BPV was found to be associated with arteriolar hyalinosis in normotensive
IgAN patients.
PMID- 28701740
TI - Comprehensive risk management for the prevention of cerebro- cardiovascular
diseases in Japan.
PMID- 28701739
TI - Hypertension with diabetes mellitus: significance from an epidemiological
perspective for Japanese.
AB - The prevalence of both hypertension and diabetes mellitus is increasing
worldwide. Both diseases lead to severe complications such as cardiovascular and
chronic kidney diseases, which increase the risk of death over a long period of
time. Therefore, the prevention and aggravation of hypertension and diabetes
mellitus are major challenges. Because few review articles have focused on the
epidemiological perspective of hypertension and diabetes mellitus, we reviewed
major observational studies mainly from Japan and from Western countries that
have reported on the prevalence of hypertension and diabetes mellitus, the
binominal risk of hypertension and diabetes mellitus, and the risk of their
coexistence. Our investigation found that approximately 50% of diabetic patients
had hypertension, and approximately 20% of hypertensive patients had diabetes
mellitus. Those with either hypertension or diabetes mellitus had a 1.5- to 2.0
fold higher risk of having both conditions. These results were similar for both
Japan and Western countries. Although comparing the results between Japan and
Western countries was difficult because the risks were estimated using widely
varying statistical analyses, it was revealed that the coexistence of
hypertension and diabetes mellitus certainly increased the risk of complications
regardless of the country. The definition, prevalence and medical treatment of
hypertension and diabetes mellitus will change in the future. For early
intervention based on the latest evidence to prevent severe complications, it is
important to accumulate epidemiological knowledge of hypertension and diabetes
mellitus and to update the evidence for both Japan and other countries.
PMID- 28701741
TI - Preparation of mono-dispersed, high energy release, core/shell structure Al
nanopowders and their application in HTPB propellant as combustion enhancers.
AB - Mono-dispersed, spherical and core/shell structure aluminum nanopowders (ANPs)
were produced massively by high energy ion beam evaporation (HEIBE). And the
number weighted average particle size of the ANPs is 98.9 nm, with an alumina
shell (3-5 nm). Benefiting from the passivation treatment, the friction, impact
and electrostatic spark sensitivity of the ANPs are almost equivalent to those of
aluminum micro powders. The result of TG-DSC indicates the active aluminum
content of ANPs is 87.14%, the enthalpy release value is 20.37 kJ/g, the specific
heat release S 1/Deltam 1* (392-611 degrees C) which determined the ability of
energy release is 19.95 kJ/g. And the value of S 1/Deltam 1* is the highest
compared with ANPs produced by other physical methods. Besides, the ANPs
perfectly compatible with hydroxyl-terminated polybutadiene (HTPB), 3 wt. % of
ANPs were used in HTPB propellant replaced micron aluminum powders, and improved
the burning rate in the 3-12 MPa pressure range and reduced the pressure
exponential by more than 31% in the 3-16 MPa pressure range. The production
technology of ANPs with excellent properties will greatly promote the application
of ANPs in the field of energetic materials such as propellant, explosive and
pyrotechnics.
PMID- 28701742
TI - Tissue-engineered trachea from a 3D-printed scaffold enhances whole-segment
tracheal repair.
AB - Long segmental repair of trachea stenosis is an intractable condition in the
clinic. The reconstruction of an artificial substitute by tissue engineering is a
promising approach to solve this unmet clinical need. 3D printing technology
provides an infinite possibility for engineering a trachea. Here, we 3D printed a
biodegradable reticular polycaprolactone (PCL) scaffold with similar morphology
to the whole segment of rabbits' native trachea. The 3D-printed scaffold was
suspended in culture with chondrocytes for 2 (Group I) or 4 (Group II) weeks,
respectively. This in vitro suspension produced a more successful reconstruction
of a tissue-engineered trachea (TET), which enhanced the overall support function
of the replaced tracheal segment. After implantation of the chondrocyte-treated
scaffold into the subcutaneous tissue of nude mice, the TET presented properties
of mature cartilage tissue. To further evaluate the feasibility of repairing
whole segment tracheal defects, replacement surgery of rabbits' native trachea by
TET was performed. Following postoperative care, mean survival time in Group I
was 14.38 +/- 5.42 days, and in Group II was 22.58 +/- 16.10 days, with the
longest survival time being 10 weeks in Group II. In conclusion, we demonstrate
the feasibility of repairing whole segment tracheal defects with 3D printed TET.
PMID- 28701743
TI - Precise detection of circular dichroism in a cluster of nano-helices by
photoacoustic measurements.
AB - Compact samples of nano-helices built by means of a focused ion beam technology
with large bandwidth and high dichroism for circular polarization are promising
for the construction of built-in-chip sensors, where the ideal transducer must be
sufficiently confined without compromising its filtering ability. Direct all
optical measurements revealed the sample's dichroic character with insufficient
details because of scattering and diffraction interference. On the other hand,
photoacoustic measurements resulted to be a possible alternative investigation,
since they directly deal with absorbed power and allow to get clear evidences of
the differential selection for the two opposite polarization states. Multi-level
numerical simulations confirmed the experimental results, proving once again the
reliability of photoacoustic technique and the versatility of this class of
dichroic artificial materials.
PMID- 28701744
TI - Massively parallel whole genome amplification for single-cell sequencing using
droplet microfluidics.
AB - Massively parallel single-cell genome sequencing is required to further
understand genetic diversities in complex biological systems. Whole genome
amplification (WGA) is the first step for single-cell sequencing, but its
throughput and accuracy are insufficient in conventional reaction platforms.
Here, we introduce single droplet multiple displacement amplification (sd-MDA), a
method that enables massively parallel amplification of single cell genomes while
maintaining sequence accuracy and specificity. Tens of thousands of single cells
are compartmentalized in millions of picoliter droplets and then subjected to
lysis and WGA by passive droplet fusion in microfluidic channels. Because single
cells are isolated in compartments, their genomes are amplified to saturation
without contamination. This enables the high-throughput acquisition of
contamination-free and cell specific sequence reads from single cells (21,000
single-cells/h), resulting in enhancement of the sequence data quality compared
to conventional methods. This method allowed WGA of both single bacterial cells
and human cancer cells. The obtained sequencing coverage rivals those of
conventional techniques with superior sequence quality. In addition, we also
demonstrate de novo assembly of uncultured soil bacteria and obtain draft genomes
from single cell sequencing. This sd-MDA is promising for flexible and scalable
use in single-cell sequencing.
PMID- 28701745
TI - A Single Dose, Randomized, Controlled Proof-Of-Mechanism Study of a Novel
Vasopressin 1a Receptor Antagonist (RG7713) in High-Functioning Adults with
Autism Spectrum Disorder.
AB - This corrects the article DOI: 10.1038/npp.2016.232.
PMID- 28701746
TI - Acute D3 Antagonist GSK598809 Selectively Enhances Neural Response During
Monetary Reward Anticipation in Drug and Alcohol Dependence.
AB - This corrects the article DOI: 10.1038/npp.2016.289.
PMID- 28701747
TI - NEAP/DUSP26 suppresses receptor tyrosine kinases and regulates neuronal
development in zebrafish.
AB - Expression of neuroendocrine-associated phosphatase (NEAP, also named as dual
specificity phosphatase 26, [DUSP26]) is restricted to neuroendocrine tissues. We
found that NEAP, but not its phosphatase-defective mutant, suppressed nerve
growth factor (NGF) receptor TrkA and fibroblast growth factor receptor 1 (FGFR1)
activation in PC12 cells upon NGF stimulation. Conversely, suppressing NEAP
expression by RNA interference enhanced TrkA and FGFR1 phosphorylation. NEAP was
capable of de-phosphorylating TrkA and FGFR1 directly in vitro. NEAP-orthologous
gene existed in zebrafish. Morpholino (MO) suppression of NEAP in zebrafish
resulted in hyper-phosphorylation of TrkA and FGFR1 as well as abnormal body
postures and small eyes. Differentiation of retina in zebrafishes with NEAP MO
treatment was severely defective, so were cranial motor neurons. Taken together,
our data indicated that NEAP/DUSP26 have a critical role in regulating TrkA and
FGFR1 signaling as well as proper development of retina and neuronal system in
zebrafish.
PMID- 28701748
TI - Gold Nanoparticles dotted Reduction Graphene Oxide Nanocomposite Based
Electrochemical Aptasensor for Selective, Rapid, Sensitive and Congener-Specific
PCB77 Detection.
AB - Gold nanoparticles (AuNP) dotted reduction graphene oxide (RGO-AuNP) is used as a
platform for an aptamer biosensor to selectively detect 3,3'4,4'-polychlorinated
biphenyls (PCB77). By anchoring aptamers onto the binding sites of RGO-AuNP and
making use of the synergy effect of RGO and AuNP, the RGO-AuNP based biosensor
exhibits superior analytical performances to AuNP based biosensor in terms of
sensitivity and repeatability. The sensitivity of RGO-AuNP based aptamers (RGO
AuNP-Ap) biosensor (226.8 MUA cm-2) is nearly two times higher than that of Au
based biosensors (AuNP-Ap/Au electrode, 147.2 MUA cm-2). The RGO-AuNP-Ap/Au
biosensor demonstrated a linear response for PCB77 concentrations between 1 pg L
1 and 10 MUg L-1, with a low limit of detection (LOD) of 0.1 pg L-1. The superb
LOD satisfies the exposure thresholds (uncontaminated water < 0.1 ng L-1) set out
by International Agency for Research on Cancer (IARC) and the Environmental
Protection Agency (EPA). The proposed biosensor can be a powerful tool for rapid,
sensitive and selective detection of PCBs on site.
PMID- 28701749
TI - Calcium-activated SK channels control firing regularity by modulating sodium
channel availability in midbrain dopamine neurons.
AB - Dopamine neurons in the substantia nigra pars compacta and ventral tegmental area
regulate behaviours such as reward-related learning, and motor control.
Dysfunction of these neurons is implicated in Schizophrenia, addiction to drugs,
and Parkinson's disease. While some dopamine neurons fire single spikes at
regular intervals, others fire irregular single spikes interspersed with bursts.
Pharmacological inhibition of calcium-activated potassium (SK) channels increases
the variability in their firing pattern, sometimes also increasing the number of
spikes fired in bursts, indicating that SK channels play an important role in
maintaining dopamine neuron firing regularity and burst firing. However, the
exact mechanisms underlying these effects are still unclear. Here, we develop a
biophysical model of a dopamine neuron incorporating ion channel stochasticity
that enabled the analysis of availability of ion channels in multiple states
during spiking. We find that decreased firing regularity is primarily due to a
significant decrease in the AHP that in turn resulted in a reduction in the
fraction of available voltage-gated sodium channels due to insufficient recovery
from inactivation. Our model further predicts that inhibition of SK channels
results in a depolarisation of action potential threshold along with an increase
in its variability.
PMID- 28701750
TI - Prognostic significance of the digit ratio after hormone therapy for prostate
cancer: a prospective multicenter study.
AB - The digit ratio has been used as a retrospective noninvasive biomarker to
investigate the putative effects of prenatal exposure to androgens. In recent
years, many scholars have paid attention to the association between 2D:4D (the
second and fourth digits) and prostatic cancer. This study explored the
prognostic significance of digit ratio in prostate cancer patients. We reviewed
the progressive status and survival of 382 prostate cancer patients who had
received hormone therapy at our institutions. Survival of clinicopathological
variables analyzed as categorical variables were determined by the log-rank test.
According to Cox's proportional hazards analysis, R2D:4D, L2D:4D, PSA at 6
month,bone metastasis were significant independent factors for prostate cancer.
The risk of any progression of prostate cancer similarly depressed with
increasing 2D:4D, for any progression (R2D:4D HR = 0.71, p = 0.003; L2D:4D HR =
0.67, p = 0.001), for cancer-specific death (R2D:4D HR = 0.67, p = 0.025; L2D:4D
HR = 0.74, p = 0.036). Digit ratio may not only have predictive value in risk but
also prognosis of prostatic cancer. This finding suggests that low 2D:4D can be
used as prognostic factors to identify patients with a poor prognosis. These
patients may benefit from more aggressive management.
PMID- 28701751
TI - Secretome of in vitro cultured human embryos contains extracellular vesicles that
are uptaken by the maternal side.
AB - Communication between embryo and maternal endometrium occurs during a specific
time frame in which implantation is possible. Here we demonstrate for the first
time that conditioned media from non-manipulated human embryos cultured in vitro
for 3 days or up to the blastocyst stage contain extracellular vesicles (EVs)
with a diameter of 50 to 200 nm and bearing the traditional microvesicle and
exosome marker proteins CD63, CD9 and ALIX. The embryonic origin of these EVs has
been confirmed by the presence of stemness gene transcripts and their enrichment
in the non-classical HLA-G protein. NANOG and POU5F1 transcripts were shown to be
contained in vesicles deriving from embryos at different stages of development.
In line with a higher detection rate of the HLA-G protein in blastocysts compared
to cleavage stage embryos, a significantly higher amount of HLA-G was found in
vesicles accumulated in spent media from day 3 to day 5 of development compared
to those isolated from the earlier stage. Uptake of dye-labeled embryo-derived
EVs by human primary endometrial epithelial and stromal cells was also
demonstrated with a fluorescence intensity signal significantly higher for cells
treated with vesicles derived from blastocysts. Based on these findings, EV
exchange may be suggested as an emerging way of communication at the maternal
fetal interface.
PMID- 28701752
TI - Suppression of VAMP2 Alters Morphology of the Tegument and Affects Glucose
uptake, Development and Reproduction of Schistosoma japonicum.
AB - Schistosomiasis caused by schsitosomes is a serious global public health concern.
The tegument that surrounds the worm is critical to the schistosomes survival.
The tegument apical membrane undergoes a continuous process of rupture and repair
owing to membranous vacuoles fusing with the plasma membrane. Vesicle-associated
membrane protein 2 (VAMP2), a member of soluble N-ethylmaleimide sensitive factor
attachment protein receptor (SNAREs) is required for membrane fusion. Here, we
used RNA interference (RNAi) to knock down the expression of VAMP2 of Schistosoma
japonicum (SjVAMP2), and both real-time PCR and western blot analysis confirmed
the suppression of this molecule, as well as the suppression of the transcript
levels of schistosome glucose transporters (SGTP1 and SGTP4), and insulin
receptors (SjIR1 and SjIR2). SjVAMP2-suppressed worms exhibited a lower
viability, and phenotypic alterations were also observed in the tegument.
Moreover, the glucose consumption of SjVAMP2-suppressed worms decreased
significantly in 4 and 6 days, respectively, as well as a significant reduction
in egg production. We also observed a significant reduction in worm burden and
hepatic eggs burden in two independent RNAi experiment in vivo, and minor
pathological changes in mice treated with SjVAMP2 specific small interfering
(si)RNA. These findings reveal that SjVAMP2 may play important roles in the
maintenance of tegument, glucose uptake, worm development and egg production in
schistosomes.
PMID- 28701753
TI - Modular approach for bimodal antibacterial surfaces combining photo-switchable
activity and sustained biocidal release.
AB - Photo-responsive antibacterial surfaces combining both on-demand photo-switchable
activity and sustained biocidal release were prepared using sequential chemical
grafting of nano-objects with different geometries and functions. The multi
layered coating developed incorporates a monolayer of near-infrared active silica
coated gold nanostars (GNS) decorated by silver nanoparticles (AgNP). This
modular approach also enables us to unravel static and photo-activated
contributions to the overall antibacterial performance of the surfaces,
demonstrating a remarkable synergy between these two mechanisms. Complementary
microbiological and imaging evaluations on both planktonic and surface-attached
bacteria provided new insights on these distinct but cooperative effects.
PMID- 28701754
TI - Clostridium perfringens alpha-toxin impairs erythropoiesis by inhibition of
erythroid differentiation.
AB - Clostridium perfringens alpha-toxin induces hemolysis of erythrocytes from
various species, but it has not been elucidated whether the toxin affects
erythropoiesis. In this study, we treated bone marrow cells (BMCs) from mice with
purified alpha-toxin and found that TER119+ erythroblasts were greatly decreased
by the treatment. A variant alpha-toxin defective in enzymatic activities,
phospholipase C and sphingomyelinase, had no effect on the population of
erythroblasts, demonstrating that the decrease in erythroblasts was dependent of
its enzymatic activities. alpha-Toxin reduced the CD71+TER119+ and CD71-TER119+
cell populations but not the CD71+TER119- cell population. In addition, alpha
toxin decreased the number of colony-forming unit erythroid colonies but not
burst-forming unit erythroid colonies, indicating that alpha-toxin preferentially
reduced mature erythroid cells compared with immature cells. alpha-Toxin slightly
increased annexinV+ cells in TER119+ cells. Additionally, simultaneous treatment
of BMCs with alpha-toxin and erythropoietin greatly attenuated the reduction of
TER119+ erythroblasts by alpha-toxin. Furthermore, hemin-induced differentiation
of human K562 erythroleukemia cells was impaired by alpha-toxin, whereas the
treatment exhibited no apparent cytotoxicity. These results suggested that alpha
toxin mainly inhibited erythroid differentiation. Together, our results provide
new insights into the biological activities of alpha-toxin, which might be
important to understand the pathogenesis of C. perfringens infection.
PMID- 28701755
TI - Microbiota composition of the koala (Phascolarctos cinereus) ocular and
urogenital sites, and their association with Chlamydia infection and disease.
AB - Disease caused by Chlamydia pecorum is characterised by ocular and urogenital
infections that can lead to blindness and infertility in koalas. However, koalas
that are infected with C. pecorum do not always progress to disease. In other
host systems, the influence of the microbiota has been implicated in either
accelerating or preventing infections progressing to disease. This study
investigates the contribution of koala urogenital and ocular microbiota to
Chlamydia infection and disease in a free ranging koala population. Using
univariate and multivariate analysis, it was found that reproductive status in
females and sexual maturation in males, were defining features in the koala
urogenital microbiota. Changes in the urogenital microbiota of koalas is
correlated with infection by the common pathogen, C. pecorum. The correlation of
microbiota composition and C. pecorum infection is suggestive of members of the
microbiota being involved in the acceleration or prevention of infections
progressing to disease. The analysis also suggests that multiple microbes are
likely to be associated with this process of disease progression, rather than a
single organism. While other Chlamydia-like organisms were also detected, they
are unlikely to contribute to chlamydial disease as they are rare members of the
urogenital and ocular microbiota communities.
PMID- 28701756
TI - Seed Metabolome Analysis of a Transgenic Rice Line Expressing Cholera Toxin B
subunit.
AB - Plant-based human vaccines have been actively developed in recent years, and rice
(Oryza sativa L.) is one of the best candidate crops for their production and
delivery. By expressing a modified cholera toxin B (CTB) subunit, we previously
developed MucoRice-CTB, a rice-based vaccine against cholera, which is caused by
infection of the intestine with the bacteria Vibrio cholerae. MucoRice-CTB lines
have been extensively characterized by whole-genome sequencing and proteome
analyses to evaluate the mutation profiles and proteome status, respectively.
Here, we report non-targeted metabolomic profiling of the MucoRice-CTB transgenic
rice line 51A (MR-CTB51A), MucoRice-RNAi (MR-RNAi), and their non-transgenic
parent line by using gas chromatography-time-of-flight mass spectrometry. The
levels of several amino acids, organic acids, carbohydrates, lipids, and
secondary metabolites were significantly increased in MR-CTB51A compared with the
non-transgenic parent line. These metabolomics results complement essential
information obtained by genome sequencing and proteomics approaches, thereby
contributing to comprehensive understanding of the properties of MucoRice-CTB as
a plant-based vaccine.
PMID- 28701757
TI - Oncolytic measles virus enhances antitumour responses of adoptive CD8+NKG2D+
cells in hepatocellular carcinoma treatment.
AB - There is an urgent need for novel effective treatment for hepatocellular
carcinoma (HCC). Oncolytic viruses (OVs) not only directly lyse malignant cells,
but also induce potent antitumour immune responses. The potency and precise
mechanisms of antitumour immune activation by attenuated measles virus remain
unclear. In this study, we investigated the potency of the measles virus vaccine
strain Edmonston (MV-Edm) in improving adoptive CD8+NKG2D+ cells for HCC
treatment. We show that MV-Edm-infected HCC enhanced the antitumour activity of
CD8+NKG2D+ cells, mediated by at least three distinct mechanisms. First, MV-Edm
infection compelled HCC cells to express the specific NKG2D ligands MICA/B, which
may contribute to the activation of CD8+NKG2D+ cells. Second, MV-Edm-infected HCC
cells stimulated CD8+NKG2D+ cells to express high level of FasL resulting in
enhanced induction of apoptosis. Third, intratumoural administration of MV-Edm
enhanced infiltration of intravenously injected CD8+NKG2D+ cells. Moreover, we
found that MV-Edm and adoptive CD8+NKG2D+ cells, either administered alone or
combined, upregulated the immune suppressive enzyme indoleamine 2,3-dioxygenase 1
(IDO1) in HCC. Elimination of IDO1 by fludarabine enhanced antitumour responses.
Taken together, our data provide a novel and clinically relevant strategy for
treatment of HCC.
PMID- 28701758
TI - Temperature dependent giant resistance anomaly in LaAlO3/SrTiO3 nanostructures.
AB - The resistance of the electron gas (2DEG) at the interface between the two band
insulators LaAlO3 (LAO) and SrTiO3 (STO) typically drops monotonically with
temperature and R/T curves during cooling and warm-up look identical for large
area structures. Here we show that if the LAO/STO is laterally restricted by
nanopatterning the resistance exhibits a temperature anomaly. Warming up
nanostructures from low temperatures leads to one or two pronounced resistance
peaks between 50 and 100 K not observed for larger dimensions. During cool-down
current filaments emerge at the domain walls that form during a structural phase
transition of the STO substrate. During warm-up the reverse phase transition can
interrupt filaments before the sheet conductivity which dominates at higher
temperature is reestablished. Due to the limited number of filaments in a
nanostructure this process can result in a complete loss of conductance. As a
consequence of these findings the transport physics extracted from experiments in
small and large area LAO/STO structures may need to be reconsidered.
PMID- 28701759
TI - Effects of combined dredging-related stressors on sponges: a laboratory approach
using realistic scenarios.
AB - Dredging can cause increased suspended sediment concentrations (SSCs), light
attenuation and sedimentation in marine communities. In order to determine the
combined effects of dredging-related pressures on adult sponges, three species
spanning different nutritional modes and morphologies were exposed to 5 treatment
levels representing realistic dredging scenarios. Most sponges survived under low
to moderate turbidity scenarios (SSCs of <= 33 mg L-1, and a daily light integral
of >=0.5 mol photons m-2 d-1) for up to 28 d. However, under the highest
turbidity scenario (76 mg L-1, 0.1 mol photons m-2 d-1) there was 20% and 90%
mortality of the phototrophic sponges Cliona orientalis and Carteriospongia
foliascens respectively, and tissue regression in the heterotrophic Ianthella
basta. All three sponge species exhibited mechanisms to effectively tolerate
dredging-related pressures in the short term (e.g. oscula closure, mucus
production and tissue regression), although reduced lipids and deterioration of
sponge health suggest that longer term exposure to similar conditions is likely
to result in higher mortality. These results suggest that the combination of high
SSCs and low light availability can accelerate mortality, increasing the
probability of biological effects, although there is considerable interspecies
variability in how adult sponges respond to dredging pressures.
PMID- 28701760
TI - Synovial tissue research: a state-of-the-art review.
AB - The synovium is the major target tissue of inflammatory arthritides such as
rheumatoid arthritis. The study of synovial tissue has advanced considerably
throughout the past few decades from arthroplasty and blind needle biopsy to the
use of arthroscopic and ultrasonographic technologies that enable easier
visualization and improve the reliability of synovial biopsies. Rapid progress
has been made in using synovial tissue to study disease pathogenesis, to stratify
patients, to discover biomarkers and novel targets, and to validate therapies,
and this progress has been facilitated by increasingly diverse and sophisticated
analytical and technological approaches. In this Review, we describe these
approaches, and summarize how their use in synovial tissue research has improved
our understanding of rheumatoid arthritis and identified candidate biomarkers
that could be used in disease diagnosis and stratification, as well as in
predicting disease course and treatment response.
PMID- 28701761
TI - Antigen-specific immunotherapies in rheumatic diseases.
AB - The main goal of antigen-specific immunotherapy (ASI) in autoimmune and rheumatic
diseases is to reprogramme or remove autoreactive cells and/or induce immune
tolerance to self-antigens. Current therapies in these diseases either treat
symptoms or slow down disease progression but are not yet curative or
preventative - disease-specific treatments are urgently needed. In contrast to
the nonspecific treatments in current use that induce generalized immune
suppression, which is associated with several adverse effects including increased
risk of infections, ASIs target a restricted subset of B cells or T cells, and
thus do not compromise systemic immunity and host defence. This Review provides a
summary of novel approaches for identifying autoepitopes and detecting and
targeting autoreactive cells that might help in the development of ASIs.
Promising approaches include the use of tolerizing peptides coupled to MHC
constructs and/or nanocompounds, tolerizing dendritic cells and antigen-specific
vaccines. Following studies in animal models of rheumatoid arthritis and systemic
lupus erythematosus, several of these strategies have now entered clinical
trials. However, to use these approaches in humans, several important limitations
must first be addressed, such as; selecting the proper immunodominant
autoantigen; identifying the optimal timing, dosing and route of administration;
finding biomarkers for monitoring the therapy; and optimizing methodology.
PMID- 28701762
TI - Different Repeat Annual Influenza Vaccinations Improve the Antibody Response to
Drifted Influenza Strains.
AB - Seasonal influenza vaccine formulas change almost every year yet information
about how this affects the antibody repertoire of vaccine recipients is
inadequate. New vaccine virus strains are selected, replacing older strains to
better match the currently circulating strains. But even while the vaccine is
being manufactured the circulating strains can evolve. The ideal response to a
seasonal vaccine would maintain antibodies toward existing strains that might
continue to circulate, and to generate cross-reactive antibodies, particularly
towards conserved influenza epitopes, potentially limiting infections caused by
newly evolving strains. Here we use the hemagglutination inhibition assay to
analyze the antibody repertoire in subjects vaccinated two years in a row with
either identical vaccine virus strains or with differing vaccine virus strains.
The data indicates that changing the vaccine formulation results in an antibody
repertoire that is better able to react with strains emerging after the vaccine
virus strains are selected. The effect is observed for both influenza A and B
strains in groups of subjects vaccinated in three different seasons. Analyses
include stratification by age and sex.
PMID- 28701763
TI - Free-of-Acrylamide SDS-based Tissue Clearing (FASTClear) for three dimensional
visualization of myocardial tissue.
AB - Several pathologic conditions of the heart lead to cardiac structural
remodelling. Given the high density and the opaque nature of the myocardium, deep
three dimensional (3D) imaging is difficult to achieve and structural analysis of
pathological myocardial structure is often limited to two dimensional images and
of thin myocardial sections. Efficient methods to obtain optical clearing of the
tissue for 3D visualisation are therefore needed. Here we describe a rapid,
simple and versatile Free-of-Acrylamide SDS-based Tissue Clearing (FASTClear)
protocol specifically designed for cardiac tissue. With this method 3D
information regarding collagen content, collagen localization and distribution
could be easily obtained across a whole 300 um-thick myocardial slice. FASTClear
does not induce structural or microstructural distortion and it can be combined
with immunostaining to identify the micro- and macrovascular networks. In
summary, we have obtained decolorized myocardial tissue suitable for high
resolution 3D imaging, with implications for the study of complex cardiac tissue
structure and its changes during pathology.
PMID- 28701764
TI - Vertically and horizontally transmitted microbial symbionts shape the gut
microbiota ontogenesis of a skin-mucus feeding discus fish progeny.
AB - Fish gut microbial communities play key functions for their hosts, but their
ontogenesis is poorly understood. Recent studies on the zebrafish suggest that
gut symbionts are recruited naturally through horizontal transmission from
environmental water. We used an alternative fish model, the discus (Symphysodon
aequifasciata), to identify the main factors driving fish gut microbiota
ontogenesis. The discus exhibits a unique parenting behavior: both discus parents
vertically feed their fry with a cutaneous mucus secretion during three weeks
post-hatching. We hypothesized that vertical microbial transmission via parental
mucus feeding, along with horizontal transmission of environmental microbial
symbionts, helps to shape the taxonomic structure of the discus fry gut
microbiota. To assess this premise, we thoroughly documented the gut microbiota
ontogenesis of a discus progeny during 100 days post-hatching. The V4 16S rRNA
gene was sequenced to assess taxonomic structure of fry gut, parent mucus, and
water samples. Our main results suggest that specific microbial symbionts both
from the parents skin mucus and environmental water play important roles in
shaping the structure of the fry gut microbiota.
PMID- 28701765
TI - The cancer-associated cell migration protein TSPAN1 is under control of androgens
and its upregulation increases prostate cancer cell migration.
AB - Cell migration drives cell invasion and metastatic progression in prostate cancer
and is a major cause of mortality and morbidity. However the mechanisms driving
cell migration in prostate cancer patients are not fully understood. We
previously identified the cancer-associated cell migration protein Tetraspanin 1
(TSPAN1) as a clinically relevant androgen regulated target in prostate cancer.
Here we find that TSPAN1 is acutely induced by androgens, and is significantly
upregulated in prostate cancer relative to both normal prostate tissue and benign
prostate hyperplasia (BPH). We also show for the first time, that TSPAN1
expression in prostate cancer cells controls the expression of key proteins
involved in cell migration. Stable upregulation of TSPAN1 in both DU145 and PC3
cells significantly increased cell migration and induced the expression of the
mesenchymal markers SLUG and ARF6. Our data suggest TSPAN1 is an androgen-driven
contributor to cell survival and motility in prostate cancer.
PMID- 28701766
TI - Collective motion of cells crawling on a substrate: roles of cell shape and
contact inhibition.
AB - Contact inhibition plays a crucial role in cell motility, wound healing, and
tumour formation. By mimicking the mechanical motion of cells crawling on a
substrate, we constructed a minimal model of migrating cells that naturally gives
rise to contact inhibition of locomotion (CIL). The model cell consists of two
disks, a front disk (a pseudopod) and a back disk (cell body), which are
connected by a finite extensible spring. Despite the simplicity of the model, the
collective behaviour of the cells is highly non-trivial and depends on both the
shape of the cells and whether CIL is enabled. Cells with a small front disk
(i.e., a narrow pseudopod) form immobile colonies. In contrast, cells with a
large front disk (e.g., a lamellipodium) exhibit coherent migration without any
explicit alignment mechanism in the model. This result suggests that crawling
cells often exhibit broad fronts because this helps facilitate alignment. After
increasing the density, the cells develop density waves that propagate against
the direction of cell migration and finally stop at higher densities.
PMID- 28701767
TI - Actomyosin and vimentin cytoskeletal networks regulate nuclear shape, mechanics
and chromatin organization.
AB - The regulation of nuclear state by the cytoskeleton is an important part of
cellular function. Actomyosin stress fibres, microtubules and intermediate
filaments have distinct and complementary roles in integrating the nucleus into
its environment and influencing its mechanical state. However, the
interconnectedness of cytoskeletal networks makes it difficult to dissect their
individual effects on the nucleus. We use simple image analysis approaches to
characterize nuclear state, estimating nuclear volume, Poisson's ratio, apparent
elastic modulus and chromatin condensation. By combining them with cytoskeletal
quantification, we assess how cytoskeletal organization regulates nuclear state.
We report for a number of cell types that nuclei display auxetic properties.
Furthermore, stress fibres and intermediate filaments modulate the mechanical
properties of the nucleus and also chromatin condensation. Conversely, nuclear
volume and its gross morphology are regulated by intracellular outward pulling
forces exerted by myosin. The modulation exerted by the cytoskeleton onto the
nucleus results in changes that are of similar magnitude to those observed when
the nucleus is altered intrinsically, inducing chromatin decondensation or cell
differentiation. Our approach allows pinpointing the contribution of distinct
cytoskeletal proteins to nuclear mechanical state in physio- and pathological
conditions, furthering our understanding of a key aspect of cellular behaviour.
PMID- 28701768
TI - Microstructural evolution during sintering of copper particles studied by
laboratory diffraction contrast tomography (LabDCT).
AB - Pressureless sintering of loose or compacted granular bodies at elevated
temperature occurs by a combination of particle rearrangement, rotation, local
deformation and diffusion, and grain growth. Understanding of how each of these
processes contributes to the densification of a powder body is still immature.
Here we report a fundamental study coupling the crystallographic imaging
capability of laboratory diffraction contrast tomography (LabDCT) with
conventional computed tomography (CT) in a time-lapse study. We are able to
follow and differentiate these processes non-destructively and in three
dimensions during the sintering of a simple copper powder sample at 1050 degrees
C. LabDCT quantifies particle rotation (to <0.05 degrees accuracy) and grain
growth while absorption CT simultaneously records the diffusion and deformation
related morphological changes of the sintering particles. We find that the rate
of particle rotation is lowest for the more highly coordinated particles and
decreases during sintering. Consequently, rotations are greater for surface
breaking particles than for more highly coordinated interior ones. Both rolling
(cooperative) and sliding particle rotations are observed. By tracking individual
grains the grain growth/shrinkage kinetics during sintering are quantified grain
by grain for the first time. Rapid, abnormal grain growth is observed for one
grain while others either grow or are consumed more gradually.
PMID- 28701769
TI - Perfluorooctane sulfonate affects intestinal immunity against bacterial
infection.
AB - Perfluorooctane sulfonate (PFOS) is an environmental contaminant that has been
manufactured to be used as surfactants and repellents in industry. Due to long
half-life for clearance and degradation, PFOS is accumulative in human body and
has potential threat to human health. Previous studies have shown the development
and function of immune cells can be affected by PFOS. Although PFOS has a high
chance of being absorbed through the oral route, whether and how PFOS affects
immune cells in the gut is unknown. Using mouse model of Citrobacter rodentium
infection, we investigated the role of PFOS on intestinal immunity. We found at
early phase of the infection, PFOS inhibited the expansion of the pathogen by
promoting IL-22 production from the group 3 innate lymphoid cell (ILC3) in an
aryl hydrocarbon receptor dependent manner. Nevertheless, persistent PFOS
treatment in mice finally led to a failure to clear the pathogen completely. At
late phase of infection, enhanced bacterial counts in PFOS treated mice were
accompanied by increased inflammatory cytokines, reduced mucin production and
dysbiosis, featured by decreased level of Lactobacillus casei, Lactobacillus
johnsonii and increased E. coli. Our study reveals a deleterious consequence in
intestinal bacterial infection caused by PFOS accumulation.
PMID- 28701770
TI - Racial and social disparities in the access to automated peritoneal dialysis -
results of a national PD cohort.
AB - The prevalence of patients on automated peritoneal dialysis (APD) is increasing
worldwide and may be guided by clinical characteristics, financial issues and
patient option. Whether socioeconomic factors at the patient level may influence
the decision for the initial peritoneal dialysis (PD) modality is unknown. This
is a prospective cohort study. The primary outcome of interest was the
probability to start PD on APD. The inclusion criteria were adult patients
incident in PD. Exclusion criteria were missing data for either race or initial
PD modality. We used a mixed-model analysis clustering patients according to
their PD center and region of the country. We included 3,901 patients of which
1,819 (46.6%) had APD as their first modality. We found a significant disparity
for race and educational level with African American patients less likely to
start on APD (Odds ratio 0.74 CI95% 0.58-0.94) compared to Whites whilst those
with greater educational levels were more likely to start on APD (Odds ratio
3.70, CI95% 2.25-6.09) compared to illiterate patients. Limiting the use of APD
in disadvantaged population may be unethical. Demographics and socioeconomic
status should not be necessarily part of the decision-making process of PD
modality choice.
PMID- 28701771
TI - Myosin 1b and F-actin are involved in the control of secretory granule
biogenesis.
AB - Hormone secretion relies on secretory granules which store hormones in endocrine
cells and release them upon cell stimulation. The molecular events leading to
hormone sorting and secretory granule formation at the level of the TGN are still
elusive. Our proteomic analysis of purified whole secretory granules or secretory
granule membranes uncovered their association with the actomyosin components
myosin 1b, actin and the actin nucleation complex Arp2/3. We found that myosin 1b
controls the formation of secretory granules and the associated regulated
secretion in both neuroendocrine cells and chromogranin A-expressing COS7 cells
used as a simplified model of induced secretion. We show that F-actin is also
involved in secretory granule biogenesis and that myosin 1b cooperates with
Arp2/3 to recruit F-actin to the Golgi region where secretory granules bud. These
results provide the first evidence that components of the actomyosin complex
promote the biogenesis of secretory granules and thereby regulate hormone sorting
and secretion.
PMID- 28701772
TI - Genetic targeting and anatomical registration of neuronal populations in the
zebrafish brain with a new set of BAC transgenic tools.
AB - Genetic access to small, reproducible sets of neurons is key to an understanding
of the functional wiring of the brain. Here we report the generation of a new
Gal4- and Cre-driver resource for zebrafish neurobiology. Candidate genes,
including cell type-specific transcription factors, neurotransmitter-synthesizing
enzymes and neuropeptides, were selected according to their expression patterns
in small and unique subsets of neurons from diverse brain regions. BAC
recombineering, followed by Tol2 transgenesis, was used to generate driver lines
that label neuronal populations in patterns that, to a large but variable extent,
recapitulate the endogenous gene expression. We used image registration to
characterize, compare, and digitally superimpose the labeling patterns from our
newly generated transgenic lines. This analysis revealed highly restricted and
mutually exclusive tissue distributions, with striking resolution of layered
brain regions such as the tectum or the rhombencephalon. We further show that a
combination of Gal4 and Cre transgenes allows intersectional expression of a
fluorescent reporter in regions where the expression of the two drivers overlaps.
Taken together, our study offers new tools for functional studies of specific
neural circuits in zebrafish.
PMID- 28701773
TI - TRIM21 is critical for survival of Toxoplasma gondii infection and localises to
GBP-positive parasite vacuoles.
AB - Interferon gamma (IFNgamma) is the major proinflammatory cytokine conferring
resistance to the intracellular vacuolar pathogen Toxoplasma gondii by inducing
the destruction of the parasitophorous vacuole (PV). We previously identified
TRIM21 as an IFNgamma-driven E3 ubiquitin ligase mediating the deposition of
ubiquitin around pathogen inclusions. Here, we show that TRIM21 knockout mice
were highly susceptible to Toxoplasma infection, exhibiting decreased levels of
serum inflammatory cytokines and higher parasite burden in the peritoneum and
brain. We demonstrate that IFNgamma drives recruitment of TRIM21 to GBP1-positive
Toxoplasma vacuoles, leading to Lys63-linked ubiquitination of the vacuole and
restriction of parasite early replication without interfering with vacuolar
disruption. As seen in vivo, TRIM21 impacted the secretion of inflammatory
cytokines. This study identifies TRIM21 as a previously unknown modulator of
Toxoplasma gondii resistance in vivo thereby extending host innate immune
recognition of eukaryotic pathogens to include E3 ubiquitin ligases.
PMID- 28701775
TI - Viral evolution: Every flu evolves in the same way.
PMID- 28701774
TI - Inhibition of beta-Glucocerebrosidase Activity Preserves Motor Unit Integrity in
a Mouse Model of Amyotrophic Lateral Sclerosis.
AB - Recent metabolomic reports connect dysregulation of glycosphingolipids,
particularly ceramide and glucosylceramide, to neurodegeneration and to motor
unit dismantling in amyotrophic lateral sclerosis at late disease stage. We
report here altered levels of gangliosides in the cerebrospinal fluid of
amyotrophic lateral sclerosis patients in early disease stage. Conduritol B
epoxide is an inhibitor of acid beta-glucosidase, and lowers glucosylceramide
degradation. Glucosylceramide is the precursor for all of the more complex
glycosphingolipids. In SOD1G86R mice, an animal model of amyotrophic lateral
sclerosis, conduritol B epoxide preserved ganglioside distribution at the
neuromuscular junction, delayed disease onset, improved motor function and
preserved motor neurons as well as neuromuscular junctions from degeneration.
Conduritol B epoxide mitigated gene dysregulation in the spinal cord and restored
the expression of genes involved in signal transduction and axonal elongation.
Inhibition of acid beta-glucosidase promoted faster axonal elongation in an in
vitro model of neuromuscular junctions and hastened recovery after peripheral
nerve injury in wild type mice. Here, we provide evidence that glycosphingolipids
play an important role in muscle innervation, which degenerates in amyotrophic
lateral sclerosis from the early disease stage. This is a first proof of concept
study showing that modulating the catabolism of glucosylceramide may be a
therapeutic target for this devastating disease.
PMID- 28701777
TI - Structural biology: Insights into bacterial microcompartments.
PMID- 28701776
TI - Microbiota: Leishmaniasis breaks the equilibrium.
PMID- 28701778
TI - The virulent, emerging genotype B of Deformed wing virus is closely linked to
overwinter honeybee worker loss.
AB - Bees are considered to be threatened globally, with severe overwinter losses of
the most important commercial pollinator, the Western honeybee, a major concern
in the Northern Hemisphere. Emerging infectious diseases have risen to prominence
due to their temporal correlation with colony losses. Among these is Deformed
wing virus (DWV), which has been frequently linked to colony mortality. We now
provide evidence of a strong statistical association between overwintering colony
decline in the field and the presence of DWV genotype-B (DWV-B), a genetic
variant of DWV that has recently been shown to be more virulent than the original
DWV genotype-A. We link the prevalence of DWV-B directly to a quantitative
measure of overwinter decline (workforce mortality) of honeybee colonies in the
field. We demonstrate that increased prevalence of virus infection in individual
bees is associated with higher overwinter mortality. We also observed a
substantial reduction of infected colonies in the spring, suggesting that virus
infected individuals had died during the winter. Our findings demonstrate that
DWV-B, plus possible A/B recombinants exhibiting DWV-B at PCR primer binding
sites, may be a major cause of elevated overwinter honeybee loss. Its potential
emergence in naive populations of bees may have far-reaching ecological and
economic impacts.
PMID- 28701779
TI - Clustering on Magnesium Surfaces - Formation and Diffusion Energies.
AB - The formation and diffusion energies of atomic clusters on Mg surfaces determine
the surface roughness and formation of faulted structure, which in turn affect
the mechanical deformation of Mg. This paper reports first principles density
function theory (DFT) based quantum mechanics calculation results of atomic
clustering on the low energy surfaces {0001} and [Formula: see text]. In
parallel, molecular statics calculations serve to test the validity of two
interatomic potentials and to extend the scope of the DFT studies. On a {0001}
surface, a compact cluster consisting of few than three atoms energetically
prefers a face-centered-cubic stacking, to serve as a nucleus of stacking fault.
On a [Formula: see text], clusters of any size always prefer hexagonal-close
packed stacking. Adatom diffusion on surface [Formula: see text] is high
anisotropic while isotropic on surface (0001). Three-dimensional Ehrlich
Schwoebel barriers converge as the step height is three atomic layers or thicker.
Adatom diffusion along steps is via hopping mechanism, and that down steps is via
exchange mechanism.
PMID- 28701780
TI - High-throughput Identification and Characterization of Two-dimensional Materials
using Density functional theory.
AB - We introduce a simple criterion to identify two-dimensional (2D) materials based
on the comparison between experimental lattice constants and lattice constants
mainly obtained from Materials-Project (MP) density functional theory (DFT)
calculation repository. Specifically, if the relative difference between the two
lattice constants for a specific material is greater than or equal to 5%, we
predict them to be good candidates for 2D materials. We have predicted at least
1356 such 2D materials. For all the systems satisfying our criterion, we manually
create single layer systems and calculate their energetics, structural,
electronic, and elastic properties for both the bulk and the single layer cases.
Currently the database consists of 1012 bulk and 430 single layer materials, of
which 371 systems are common to bulk and single layer. The rest of calculations
are underway. To validate our criterion, we calculated the exfoliation energy of
the suggested layered materials, and we found that in 88.9% of the cases the
currently accepted criterion for exfoliation was satisfied. Also, using
molybdenum telluride as a test case, we performed X-ray diffraction and Raman
scattering experiments to benchmark our calculations and understand their
applicability and limitations. The data is publicly available at the website
http://www.ctcms.nist.gov/~knc6/JVASP.html.
PMID- 28701781
TI - Identification for Differential Localization of Putative Corneal Epithelial Stem
Cells in Mouse and Human.
AB - Human Corneal epithelial stem cells (CESCs) have been identified to reside in
limbus for more than 2 decades. However, the precise location of CESCs in other
mammalian remains elusive. This study was to identify differential localization
of putative CESCs in mice. Through a series of murine corneal cross-sections from
different directions, we identified that anatomically and morphologically the
murine limbus is composed of the thinnest epithelium and the thinnest stroma
without any palisades of Vogt-like niche structure. The cells expressing five of
stem/progenitor cell markers are localized in basal layer of entire murine
corneal epithelium. BrdU label-retaining cells, a key characteristic of
epithelial stem cells, are detected in both limbal and central cornea of mouse
eye. Functionally, corneal epithelium can be regenerated in cultures from central
and limbal explants of murine cornea. Such a distribution of mouse CESCs is
different from human cornea, where limbal stem cell concept has been well
established and accepted. We are aware that some new evidence supports limbal
stem cell concept in mouse recently. However, it is important to know that
central cornea may provide an alternative source of stem cells when one utilizes
mice as animal model for corneal research.
PMID- 28701782
TI - Haeme oxygenase protects against UV light DNA damages in the retina in clock
dependent manner.
AB - In the present study, we showed that in the retina of Drosophila, the expression
of the ho gene, encoding haeme oxygenase (HO), is regulated by light but only at
the beginning of the day. This timing must be set by the circadian clock as light
pulses applied at other time points during the day do not increase the ho mRNA
level. Moreover, light-induced activation of HO does not depend on the canonical
phototransduction pathway but instead involves cryptochrome and is enhanced by
ultraviolet (UV) light. Interestingly, the level of DNA damage in the retina
after UV exposure was inversely related to the circadian oscillation of the ho
mRNA level during the night, being the highest when the HO level was low and
reversed during the day. Accordingly, induction of HO by hemin was associated
with low DNA damage, while inhibition of HO activity by SnPPIX aggravated the
damage. Our data suggest that HO acts in the retina to decrease oxidative DNA
damage in photoreceptors caused by UV-rich light in the morning.
PMID- 28701783
TI - Circulating miR-323-3p is a biomarker for cardiomyopathy and an indicator of
phenotypic variability in Friedreich's ataxia patients.
AB - MicroRNAs (miRNAs) are noncoding RNAs that contribute to gene expression
modulation by regulating important cellular pathways. In this study, we used
small RNA sequencing to identify a series of circulating miRNAs in blood samples
taken from Friedreich's ataxia patients. We were thus able to develop a miRNA
biomarker signature to differentiate Friedreich's ataxia (FRDA) patients from
healthy people. Most research on FDRA has focused on understanding the role of
frataxin in the mitochondria, and a whole molecular view of pathological pathways
underlying FRDA therefore remains to be elucidated. We found seven differentially
expressed miRNAs, and we propose that these miRNAs represent key mechanisms in
the modulation of several signalling pathways that regulate the physiopathology
of FRDA. If this is the case, miRNAs can be used to characterize phenotypic
variation in FRDA and stratify patients' risk of cardiomyopathy. In this study,
we identify miR-323-3p as a candidate marker for phenotypic differentiation in
FRDA patients suffering from cardiomyopathy. We propose the use of dynamic miRNAs
as biomarkers for phenotypic characterization and prognosis of FRDA.
PMID- 28701784
TI - Familial Associations of Colorectal Cancer with Other Cancers.
AB - Colorectal cancer (CRC) has a strong familial component which extends to
discordant cancers (ie non-CRC tumors). This is best seen in cancer syndromes
such as hereditary non-polyposis colorectal cancer (HNPCC) which predisposes to
several tumor types. Population-based family studies have also found discordant
associations for CRC but they have included cancers which manifest in HNPCC, and
there is no convincing evidence of discordant associations beyond the known
syndromes. We address familial associations of non-CRC tumors with CRC using the
resources of the Swedish Family-Cancer Database and applying a powerful approach
of assessing familial relative risks in families of increasing numbers of
patients with discordant cancers. Among 1.8 million cancer patients and over
200,000 CRC cases consistent familial associations of CRC was observed for
several HNPCC related cancers. However, for small intestinal, pancreatic and
nervous system cancers RRs remained essentially unchanged when potential HNPCC
families were excluded, suggesting involvement of genes not related to HNPCC. Two
independent associations of CRC were found for melanoma, thyroid and eye cancers
and these appeared not to be related to known syndromes. A number of other
cancers associated with CRC in single analyses and independent studies are
required to assess the relevance of such findings.
PMID- 28701785
TI - Possible electric field induced indirect to direct band gap transition in MoSe2.
AB - Direct band-gap semiconductors play the central role in optoelectronics. In this
regard, monolayer (ML) MX2 (M = Mo, W; X = S, Se) has drawn increasing attention
due to its novel optoelectronic properties stemming from the direct band-gap and
valley degeneracy. Unfortunately, the more practically usable bulk and multilayer
MX2 have indirect-gaps. It is thus highly desired to turn bulk and multilayer MX2
into direct band-gap semiconductors by controlling external parameters. Here, we
report angle-resolved photoemission spectroscopy (ARPES) results from Rb dosed
MoSe2 that suggest possibility for electric field induced indirect to direct band
gap transition in bulk MoSe2. The Rb concentration dependent data show detailed
evolution of the band-gap, approaching a direct band-gap state. As ionized Rb
layer on the surface provides a strong electric field perpendicular to the
surface within a few surface layers of MoSe2, our data suggest that direct band
gap in MoSe2 can be achieved if a strong electric field is applied, which is a
step towards optoelectronic application of bulk materials.
PMID- 28701786
TI - Costly neighbours: Heterospecific competitive interactions increase metabolic
rates in dominant species.
AB - The energy costs of self-maintenance (standard metabolic rate, SMR) vary
substantially among individuals within a population. Despite the importance of
SMR for understanding life history strategies, ecological sources of SMR
variation remain only partially understood. Stress-mediated increases in SMR are
common in subordinate individuals within a population, while the direction and
magnitude of the SMR shift induced by interspecific competitive interactions is
largely unknown. Using laboratory experiments, we examined the influence of con-
and heterospecific pairing on SMR, spontaneous activity, and somatic growth rates
in the sympatrically living juvenile newts Ichthyosaura alpestris and Lissotriton
vulgaris. The experimental pairing had little influence on SMR and growth rates
in the smaller species, L. vulgaris. Individuals exposed to con- and
heterospecific interactions were more active than individually reared newts. In
the larger species, I. alpestris, heterospecific interactions induced SMR to
increase beyond values of individually reared counterparts. Individuals from
heterospecific pairs and larger conspecifics grew faster than did newts in other
groups. The plastic shift in SMR was independent of the variation in growth rate
and activity level. These results reveal a new source of individual SMR variation
and potential costs of co-occurrence in ecologically similar taxa.
PMID- 28701787
TI - Avian reovirus p17 and sigmaA act cooperatively to downregulate Akt by
suppressing mTORC2 and CDK2/cyclin A2 and upregulating proteasome PSMB6.
AB - Although we have shown that avian reovirus (ARV) p17-mediated inhibition of Akt
leads to induction of autophagy, the precise mechanisms remain largely unknown.
This study has identified a specific mechanism by which ARV coordinately
regulates the degradation of ribosomal proteins by p17-mediated activation of E3
ligase MDM2 that targets ribosomal proteins and by sigmaA-mediated upregulation
of proteasome PSMB6. In addition to downregulating ribosomal proteins, p17
reduces mTORC2 assembly and disrupts mTORC2-robosome association, both of which
inactivate mTORC2 leading to inhibition of Akt phosphorylation at S473.
Furthermore, we discovered that p17 binds to and inhibits the CDK2/cyclin A2
complex, further inhibiting phosphorylation of Akt S473. The negative effect of
p17 on mTORC2 assembly and Akt phosphorylation at S473 is reversed in cells
treated with insulin or overexpression of CDK2. The carboxyl terminus of p17 is
necessary for interaction with CDK2 and for induction of autophagy. Furthermore,
p17-mediated upregulation of LC3-II could be partially reversed by overexpression
of CDK2. The present study provides mechanistic insights into cooperation between
p17 and sigmaA proteins of ARV to negatively regulate Akt by downregulating
complexes of mTORC2 and CDK2/cyclin A2 and upregulating PSMB6, which together
induces autophagy and cell cycle arrest and benefits virus replication.
PMID- 28701788
TI - Atomic-Layer-Deposition Assisted Formation of Wafer-Scale Double-Layer Metal
Nanoparticles with Tunable Nanogap for Surface-Enhanced Raman Scattering.
AB - A simple high-throughput approach is presented in this work to fabricate the Au
nanoparticles (NPs)/nanogap/Au NPs structure for surface enhanced Raman
scattering (SERS). This plasmonic nanostructure can be prepared feasibly by the
combination of rapid thermal annealing (RTA), atomic layer deposition (ALD) and
chemical etching process. The nanogap size between Au NPs can be easily and
precisely tuned to nanometer scale by adjusting the thickness of sacrificial ALD
Al2O3 layer. Finite-difference time-domain (FDTD) simulation data indicate that
most of enhanced field locates at Au NPs nanogap area. Moreover, Au
NPs/nanogap/Au NPs structure with smaller gap exhibits the larger electromagnetic
field. Experimental results agree well with FDTD simulation data, the plasmonic
structure with smaller nanogap size has a stronger Raman intensity. There is
highly strong plasmonic coupling in the Au nanogap, so that a great SERS effect
is obtained when detecting methylene blue (MB) molecules with an enhancement
factor (EF) over 107. Furthermore, this plasmonic nanostructure can be designed
on large area with high density and high intensity hot spots. This strategy of
producing nanoscale metal gap on large area has significant implications for
ultrasensitive Raman detection and practical SERS application.
PMID- 28701789
TI - Mental workload and neural efficiency quantified in the prefrontal cortex using
fNIRS.
AB - An improved understanding of how the brain allocates mental resources as a
function of task difficulty is critical for enhancing human performance.
Functional near infrared spectroscopy (fNIRS) is a field-deployable optical brain
monitoring technology that provides a direct measure of cerebral blood flow in
response to cognitive activity. We found that fNIRS was sensitive to variations
in task difficulty in both real-life (flight simulator) and laboratory settings
(tests measuring executive functions), showing increased concentration of
oxygenated hemoglobin (HbO2) and decreased concentration of deoxygenated
hemoglobin (HHb) in the prefrontal cortex as the tasks became more complex.
Intensity of prefrontal activation (HbO2 concentration) was not clearly
correlated to task performance. Rather, activation intensity shed insight on the
level of mental effort, i.e., how hard an individual was working to accomplish a
task. When combined with performance, fNIRS provided an estimate of the
participants' neural efficiency, and this efficiency was consistent across levels
of difficulty of the same task. Overall, our data support the suitability of
fNIRS to assess the mental effort related to human operations and represents a
promising tool for the measurement of neural efficiency in other contexts such as
training programs or the clinical setting.
PMID- 28701790
TI - Membrane progesterone receptor beta (mPRbeta/Paqr8) promotes progesterone
dependent neurite outgrowth in PC12 neuronal cells via non-G protein-coupled
receptor (GPCR) signaling.
AB - Recently, sex steroid membrane receptors garnered world-wide attention because
they may be related to sex hormone-mediated unknown rapid non-genomic action that
cannot be currently explained by their genomic action via nuclear receptors.
Progesterone affects cell proliferation and survival via non-genomic effects. In
this process, membrane progesterone receptors (mPRalpha, mPRbeta, mPRgamma,
mPRdelta, and mPRepsilon) were identified as putative G protein-coupled receptors
(GPCRs) for progesterone. However, the structure, intracellular signaling, and
physiological functions of these progesterone receptors are still unclear. Here,
we identify a molecular mechanism by which progesterone promotes neurite
outgrowth through mPRbeta (Paqr8) activation. Mouse mPRbeta mRNA was specifically
expressed in the central nervous system. It has an incomplete GPCR topology,
presenting 6 transmembrane domains and did not exhibit typical GPCR signaling.
Progesterone-dependent neurite outgrowth was exhibited by the promotion of ERK
phosphorylation via mPRbeta, but not via other progesterone receptors such as
progesterone membrane receptor 1 (PGRMC-1) and nuclear progesterone receptor in
nerve growth factor-induced neuronal PC12 cells. These findings provide new
insights of regarding the non-genomic action of progesterone in the central
nervous system.
PMID- 28701791
TI - Multi-photon absorption enhancement by dual-wavelength double-pulse laser
irradiation for efficient dicing of sapphire wafers.
AB - The evidence of multi-photon absorption enhancement by the dual-wavelength double
pulse laser irradiation in transparent sapphire was demonstrated experimentally
and explained theoretically for the first time. Two collinearly combined laser
beams with the wavelengths of 1064 nm and 355 nm, inter-pulse delay of 0.1 ns,
and pulse duration of 10 ps were used to induce intra-volume modifications in
sapphire. The theoretical prediction of using a particular orientation angle of
15 degrees of the half-wave plate for the most efficient absorption of laser
irradiation is in good agreement with the experimental data. The new innovative
effect of multi-photon absorption enhancement by dual-wavelength double-pulse
irradiation allowed utilisation of the laser energy up to four times more
efficiently for initiation of internal modifications in sapphire. The new
absorption enhancement effect has been used for efficient intra-volume dicing and
singulation of transparent sapphire wafers. The dicing speed of 150 mm/s was
achieved for the 430 MUm thick sapphire wafer by using the laser power of 6.8 W
at the repetition rate of 100 kHz. This method opens new opportunities for the
manufacturers of the GaN-based light-emitting diodes by fast and precise
separation of sapphire substrates.
PMID- 28701792
TI - Curvature controlled defect dynamics in topological active nematics.
AB - We study the spatiotemporal patterns that emerge when an active nematic film is
topologically constraint. These topological constraints allow to control the non
equilibrium dynamics of the active system. We consider ellipsoidal shapes for
which the resulting defects are 1/2 disclinations and analyze the relation
between their location and dynamics and local geometric properties of the
ellipsoid. We highlight two dynamic modes: a tunable periodic state that
oscillates between two defect configurations on a spherical shape and a tunable
rotating state for oblate spheroids. We further demonstrate the relation between
defects and high Gaussian curvature and umbilical points and point out limits for
a coarse-grained description of defects as self-propelled particles.
PMID- 28701793
TI - The miR-29 transcriptome in endocrine-sensitive and resistant breast cancer
cells.
AB - Aberrant microRNA expression contributes to breast cancer progression and
endocrine resistance. We reported that although tamoxifen stimulated miR-29b-1/a
transcription in tamoxifen (TAM)-resistant breast cancer cells, ectopic
expression of miR-29b-1/a did not drive TAM-resistance in MCF-7 breast cancer
cells. However, miR-29b-1/a overexpression significantly repressed TAM-resistant
LCC9 cell proliferation, suggesting that miR-29b-1/a is not mediating TAM
resistance but acts as a tumor suppressor in TAM-resistant cells. The target
genes mediating this tumor suppressor activity were unknown. Here, we identify
miR-29b-1 and miR-29a target transcripts in both MCF-7 and LCC9 cells. We find
that miR-29b-1 and miR-29a regulate common and unique transcripts in each cell
line. The cell-specific and common downregulated genes were characterized using
the MetaCore Gene Ontology (GO) enrichment analysis algorithm. LCC9-sepecific miR
29b-1/a-regulated GO processes include oxidative phosphorylation, ATP metabolism,
and apoptosis. Extracellular flux analysis of cells transfected with anti- or pre
miR-29a confirmed that miR-29a inhibits mitochondrial bioenergetics in LCC9
cells. qPCR,luciferase reporter assays, and western blot also verified the ATP
synthase subunit genes ATP5G1 and ATPIF1 as bone fide miR29b-1/a targets. Our
results suggest that miR-29 repression of TAM-resistant breast cancer cell
proliferation is mediated in part through repression of genes important in
mitochondrial bioenergetics.
PMID- 28701794
TI - 3D NiO hollow sphere/reduced graphene oxide composite for high-performance
glucose biosensor.
AB - : The 3D NiO hollow sphere/reduced graphene oxide (rGO) composite was synthesized
according to the coordinating etching and precipitating process by using Cu2O
nanosphere/graphene oxide (GO) composite as template. The morphology, structure,
and composition of the materials were characterized by SEM, TEM, HRTEM, XPS, and
Raman spectra, and the electrochemical properties were studied by cyclic
voltammetry (CV), electrochemical impedance spectroscopy (EIS), and amperometry.
Moreover, the electrochemical activity of the composite materials with different
morphologies were also investigated, which indicating a better combination of the
NiO hollow sphere and the rGO. Used as glucose sensing material, the 3D NiO
hollow sphere/rGO composite modified electrode exhibits high sensitivity of ~2.04
mA mM-1 cm-2, quick response time of less than 5 s, good stability, selectivity,
and reproducibility. Its application for the detection of glucose in human blood
serum sample shows acceptable recovery and R.S.D. VALUES: The outstanding glucose
sensing performance should be attributed to the unique 3D hierarchical porous
superstructure of the composite, especially for its enhanced electron-transfer
kinetic properties.
PMID- 28701795
TI - Terahertz Spectroscopic Diagnosis of Myelin Deficit Brain in Mice and Rhesus
Monkey with Chemometric Techniques.
AB - While myelin deficit of the central nervous system leads to several severe
diseases, the definitive diagnostic means are lacking. We proposed and performed
terahertz time-domain spectroscopy (THz-TDS) combined with chemometric techniques
to discriminate and evaluate the severity of myelin deficit in mouse and rhesus
monkey brains. The THz refractive index and absorption coefficient of paraffin
embedded brain tissues from both normal and mutant dysmyelinating mice are shown.
Principal component analysis of time-domain THz signal (PCA-tdTHz) and absorption
refractive index relation of THz spectrum identified myelin deficit without
exogenous labeling or any pretreatment. Further, with the established PCA-tdTHz,
we evaluated the severity of myelin deficit lesions in rhesus monkey brain
induced by experimental autoimmune encephalomyelitis, which is the most-studied
animal model of multiple sclerosis. The results well matched the pathological
analysis, indicating that PCA-tdTHz is a quick, powerful, evolving tool for
identification and evaluation myelin deficit in preclinical animals and
potentially in para-clinical human biopsy.
PMID- 28701796
TI - CaMK II gamma down regulation protects dorsal root ganglion neurons from
ropivacaine hydrochloride neurotoxicity.
AB - T-type calcium channels are intimately involved in the local anesthetics
neurotoxicity. Does CaMKIIgamma regulate T-type calcium currents in local
anesthetics neurotoxicity? This study generated pAd-CaMKIIgamma and pAd-shRNA
adenovirus vectors to up- and down-regulate CaMKIIgamma mRNA expression in dorsal
root ganglion neurons (DRG). Normal DRG (Normal group), empty vector DRG (Empty
vector group), pAd-CaMKIIgamma DRG (pAd-CaMKIIgamma group) and pAd-shRNA DRG (pAd
shRNA group) were treated or untreated with 3 mM ropivacaine hydrochloride for 4
h. Cell viability, apoptosis rate, CaMKIIgamma, pCaMKIIgamma, Cav3.2, and Cav3.3
expression were detected. Ultrastructural changes in DRG were observed under a
transmission electron microscope. The results demonstrated that the cell
viability of DRG treated with ropivacaine hydrochloride decreased markedly, the
apoptosis rate, CaMKIIgamma, pCaMKIIgamma, Cav3.2, Cav3.3 expression increased
significantly. CaMKIIgamma up-regulation aggravated ropivacaine hydrochloride
induced cell damage and increased Cav3.2 and Cav3.3 expression. In conclusion,
CaMKIIgamma regulated Cav3.2 and Cav3.3 expression in DRG, which was involved
with ropivacaine hydrochloride-induced cell injury.
PMID- 28701797
TI - Antimicrobial effect of blue light using Porphyromonas gingivalis pigment.
AB - The development of antibiotics cannot keep up with the speed of resistance
acquired by microorganisms. Recently, the development of antimicrobial
photodynamic therapy (aPDT) has been a necessary antimicrobial strategy against
antibiotic resistance. Among the wide variety of bacteria found in the oral
flora, Porphyromonas gingivalis (P. gingivalis) is one of the etiological agents
of periodontal disease. aPDT has been studied for periodontal disease, but has
risks of cytotoxicity to normal stained tissue. In this study, we performed aPDT
using protoporphyrin IX (PpIX), an intracellular pigment of P. gingivalis,
without an external photosensitizer. We confirmed singlet oxygen generation by
PpIX in a blue-light irradiation intensity-dependent manner. We discovered that
blue-light irradiation on P. gingivalis is potentially bactericidal. The
sterilization mechanism seems to be oxidative DNA damage in bacterial cells.
Although it is said that no resistant bacteria will emerge using aPDT, the
conventional method relies on an added photosensitizer dye. PpIX in P. gingivalis
is used in energy production, so aPDT applied to PpIX of P. gingivalis should
limit the appearance of resistant bacteria. This approach not only has potential
as an effective treatment for new periodontal diseases, but also offers potential
antibacterial treatment for multiple drug resistant bacteria.
PMID- 28701798
TI - Cognitive behavioral therapy as an adjunct treatment for Pakistani men with ED.
AB - The goal of this study was to determine potential positive effects of cognitive
behavioral therapy (CBT) on Pakistani men with ED who were undergoing treatment
with a PDE-5 inhibitor. We used a pre-post research design comparing men with and
without adjunctive CBT. Men in the two groups were compared to determine whether
CBT improved sexual function, as measured by the International Index of Erectile
Function (IIEF). A total of 60 individuals diagnosed with ED completed the study.
Participants were systematically assigned to one of two groups, the CBT group or
the control group. The sample was drawn from outpatients referred through several
hospitals in Islamabad. All men showed improvement in sexual functioning over the
course of the study, though post treatment, men in the CBT group showed greater
improvement on IIEF subscales of erectile functioning, orgasmic function,
intercourse satisfaction and overall satisfaction than those in the control
group. CBT can be considered an effective and supportive means for achieving
better sexual outcomes for Pakistani men taking PDE-5 inhibitors for erectile
problems.
PMID- 28701799
TI - A Robust Method for Inferring Network Structures.
AB - Inferring the network structure from limited observable data is significant in
molecular biology, communication and many other areas. It is challenging,
primarily because the observable data are sparse, finite and noisy. The
development of machine learning and network structure study provides a great
chance to solve the problem. In this paper, we propose an iterative smoothing
algorithm with structure sparsity (ISSS) method. The elastic penalty in the model
is introduced for the sparse solution, identifying group features and avoiding
over-fitting, and the total variation (TV) penalty in the model can effectively
utilize the structure information to identify the neighborhood of the vertices.
Due to the non-smoothness of the elastic and structural TV penalties, an
efficient algorithm with the Nesterov's smoothing optimization technique is
proposed to solve the non-smooth problem. The experimental results on both
synthetic and real-world networks show that the proposed model is robust against
insufficient data and high noise. In addition, we investigate many factors that
play important roles in identifying the performance of ISSS.
PMID- 28701800
TI - Design, transform and control of optical field in discrete optical system: an
example.
AB - A discrete optical system can broaden the spatial distribution of the input light
through optical coupling in array waveguides, just like diffraction in continuous
media. Here, we theoretically demonstrate several kinds of control methods of
optical field propagation in a discrete optical system, which is composed of an
Airy fiber with two perpendicular arrayed cores. A brief transform mechanism
between Gaussian and Airy beam propagation in such a fiber is presented. The
wavefront of the output beam from the Airy fiber is actually dependent on the
phased arrayed modulation of coupling array cores. Except the optical wavelength
changing, we propose two new methods, including fiber length and bending-induced
refractive-index changing, to accomplish that modulation. The calculation results
show that these new methods are very effective for the Airy phase modulation. By
combining these methods and controlling the corresponding parameters, the
Gaussian beam, the one-dimension Airy beam, and the two-dimension Airy beam can
be obtained by one same Airy fiber. These methods are also generally applicable
to the other discrete optical system and can be extended to generate any other
types of optical beams, such as Bessel beams and Mathieu beams.
PMID- 28701801
TI - Adipose Tissue Formation Utilizing Fat Flap Distraction Technique.
AB - Co-regulation between adipocytes and supporting vasculature is considered an
important process in adipose tissue generation. The objective of this study was
to evaluate the mechanical and biological effects of a distraction technique on
adipose tissue formation and maintenance. Based on the hypothesis that fat flaps
gradually receding from each other can develop an adipose tissue construct,
perforated polycarbonate syringe-shaped chambers were implanted in a rabbit
model. Latency (1 week) and distraction (3 weeks) periods were followed by a
consolidation period in the experimental groups (4, 8, and 12 weeks). In the
distraction group, the volume of fat pad gradually increased up to 16 weeks. A
transition zone was observed at 8 weeks, indicating the initiation of tissue
generation. Histomorphologic analysis showed adipose and collagen connective
tissue at 8 weeks. At 16 weeks, the relative composition was altered
significantly. Adipose components occupied most of the tissue, and connective
tissue was reduced. Blood vessels with endothelial lining were noted adjacent to
adipocyte clusters, as well as in inter-adipocyte areas. The vessels had
increased in number and were evenly distributed by 16 weeks. Our distraction
technique produced more balanced adipose tissue generation than a non-distraction
method, with co-development of adipose and vascular tissues.
PMID- 28701802
TI - Osthole improves function of periodontitis periodontal ligament stem cells via
epigenetic modification in cell sheets engineering.
AB - Inflammatory microenvironment causes the change of epigenetic modification in
periodontal ligament stem cells derived from periodontitis tissues (P-PDLSCs),
which results in defective osteogenic differentiation compared to cells from
healthy tissues. It's urgent to explore therapeutic strategies aimed at
epigenetic targets associated with the regenerative ability of PDLSCs. Osthole, a
small-molecule compound extracted from Chinese herbs, has been documented to
promote osteogenesis and cell sheets formation of healthy PDLSCs. However,
whether osthole shows same effect on P-PDLSCs and the mechanism of promotive
effect is still unknown. The purpose of this study was to determine whether
Osthole could restore defective osteogenic differentiation of P-PDLSCs via
epigenetic modification. We demonstrated that 10-7 Mol/L of Osthole was the best
concentration for osteogenic differentiation and proliferation of P-PDLSCs.
Mechanistically, we also found that Osthole upregulated MOZ and MORF, histone
acetylases that specifically catalyze acetylation of Histone3 lisine9 (H3K9) and
Histone3 lisine14 (H3K14), which are key regulators in osteogenic differentiation
of P-PDLSCs. Furthermore, Osthole treatment improved cell sheet formation and
enhanced the bone formation of PDLSC sheets in animal models of periodontitis.
Our study suggests that Osthole is a promising drug to cure periodontitis via
regulating epigenetic modification in cell sheets engineering.
PMID- 28701803
TI - On the generalization of attitude accessibility after repeated attitude
expression.
AB - The more accessible an attitude is, the stronger is its influence on information
processing and behavior. Accessibility can be increased through attitude
rehearsal, but it remains unknown whether attitude rehearsal also affects the
accessibility of related attitudes. To investigate this hypothesis, participants
in an experimental condition repeatedly expressed their attitudes towards
exemplars of several semantic categories during an evaluative categorization
task. Participants in a control condition performed a non-evaluative task with
the same exemplars and evaluated unrelated attitude objects. After a 30-minute
interval, participants in the experimental condition were faster than controls to
evaluate not only the original exemplars but also novel exemplars of the same
categories. This finding suggests that the effect of attitude rehearsal on
accessibility generalizes to attitudes towards untrained but semantically related
attitude objects. (c) 2016 The Authors. European Journal of Social Psychology
published by John Wiley & Sons, Ltd.
PMID- 28701804
TI - How Dangerous Is Obesity? Issues in Measurement and Interpretation.
PMID- 28701805
TI - Identification and quantification of carbonyl-containing alpha-pinene ozonolysis
products using O-tert-butylhydroxylamine hydrochloride.
AB - The yields of carbonyl-containing reaction products from the ozonolysis of alpha
pinene have been investigated using concentrations of ozone found in the indoor
environment ([O3] <= 100 ppb). An impinger was used to collect gas-phase
oxidation products in water, where the derivatization agent O-tert
butylhydroxylamine hydrochloride (TBOX) and gas chromatography-mass spectrometry
were used to identify carbonyl-containing species. Seven carbonyl-containing
products were observed. The yield of the primary product, pinonaldehyde was
measured to be 76 %. Using cyclohexane as a hydroxyl radical (OH) scavenger, the
yield of pinonaldehyde decreased to 46 %, indicating the influence secondary OH
radicals have on alpha-pinene ozonolysis products. Furthermore, the use of TBOX,
a small molecular weight derivatization agent, allowed for the acquisition of the
first mass spectral data of oxopinonaldehyde, a tricarbonyl reaction product of
alpha-pinene ozonolysis. The techniques described herein allow for an effective
method for the collection and identification of terpene oxidation products in the
indoor environment.
PMID- 28701806
TI - Meteorological and landscape influences on pollen beetle immigration into oilseed
rape crops.
AB - Heavy reliance on pesticide inputs to maintain crop yields has been an important
aspect of agricultural intensification. Insecticide use has had detrimental
impacts on pollinators and natural pest control agents, contributing to a decline
in associated ecosystem services, and has also led to resistance development in
pest populations. Throughout Europe, in oilseed rape (Brassica napus L.) crops,
prophylactic use of insecticides against pollen beetles (Meligethes aeneus F.
also known as Brassicogethes aeneus) has led to such issues, and there is an
urgent need to develop more sustainable pest management practices for the crop.
Although advice is available to oilseed rape growers regarding control
thresholds, it may not be adhered to due to the expense of pollen beetle
monitoring relative to the inexpensive cost of pyrethroid insecticides. Thus, the
key to reducing prophylactic insecticide applications may lie with improved, less
labour intensive methods of pollen beetle monitoring. For these to be realized, a
better understanding is needed of the effects of agri-landscape features and
meteorological conditions on pollen beetle immigration into the crop. In this
study, based on data from four years of pollen beetle monitoring on a total of 41
field sites, we model the effects of meteorological (wind speed and direction,
rainfall and accumulated temperature) and landscape (areas of woodland,
residential gardens, the current and previous seasons' oilseed rape crops, and
lengths of hedgerows and treelines) variables on directional sticky trap catches,
at both the single trap and field scales. Meteorological variables, particularly
accumulated temperature and wind speed were more important than landscape
variables in predicting the abundance of pollen beetles immigrating into OSR
fields. Sticky traps that were facing downwind caught more beetles than those
that were facing across-wind or upwind; this is the first study to show at a
landscape-scale, direct evidence for use of upwind anemotaxis by pollen beetles
at the point of entry during immigration into the crop. At the field scale, the
area of oilseed rape grown in the previous season was found to be positively
related to trap catch, but no relationships with other landscape variables were
found. Optimally-placed monitoring traps could complement existing decision
support systems to reduce pollen beetle monitoring effort and encourage use of
insecticides only when control thresholds are breached, thus enhancing the
sustainability of oilseed rape production. Knowledge of the area of oilseed rape
crops grown during the previous season in the surrounding landscape could
contribute to risk assessment of potential pest pressure for individual OSR
crops.
PMID- 28701807
TI - Natriuretic Peptides as Biomarkers for Congestive States: The Cardiorenal
Divergence.
AB - Congestion represents the primary reason for hospitalization of patients with
heart failure and is associated with adverse outcomes. Fluid overload has been
shown to be inadequately addressed in a significant subset of these patients in
part due to lack of robust, reliable, and readily available biomarkers for
objective assessment and monitoring of therapy. Natriuretic peptides have long
been used in this setting, often in conjunction with other assessment tools such
as imaging studies. Patients presenting with concomitant cardiac and renal
dysfunction represent a unique population with regard to congestion in that the
interactions between the heart and the kidney can affect the utility and
performance of biomarkers of fluid overload. Herein, we provide an overview of
the currently available evidence on the utility of natriuretic peptides in these
patients and discuss the clinical conundrum associated with their use in the
setting of renal dysfunction. We highlight the potential divergence in the role
of natriuretic peptides for assessment of volume status in a subset of patients
with renal dysfunction who receive renal replacement therapy and call for future
research to elucidate the utility of the biomarkers in this setting.
PMID- 28701808
TI - Assembly patterns of soil-dwelling lichens after glacier retreat in the European
Alps.
AB - AIM: To assess the spatial-temporal dynamics of primary succession following
deglaciation in soil-dwelling lichen communities. LOCATION: European Alps
(Austria, Switzerland and Italy). METHODS: Five glacier forelands subjected to
relevant glacier retreat during the last century were investigated. In each
glacier foreland, three successional stages were selected at increasing distance
from the glacier, corresponding to a gradient of time since deglaciation between
25 and 160 years. In each successional stage, soil-dwelling lichens were surveyed
within five 1 * 1 m plots. In addition to a classical ecological framework, based
on species richness and composition, we applied a functional approach to better
elucidate community assembly mechanisms. RESULTS: A positive relationship was
found between species richness and time since deglaciation indicating that richer
lichen communities can be found at increasing terrain ageing. This pattern was
associated with compositional shifts, suggesting that different community
assemblages can be found along the successional stages. The analysis of beta
diversity revealed a significant nested pattern of species assemblages along the
gradient (i.e. earlier successional stages hosted a subset of the species already
established in older successional stages), while the turnover component was less
relevant. Considering functional groups, we found contrasting patterns in
relation to time since deglaciation: the incidence of species with a
cyanobacterial photobiont and those reproducing by spores decreased, while that
of species reproducing by vegetative propagules increased. MAIN CONCLUSIONS: This
study reveals that community assembly patterns of soil-dwelling lichens in alpine
glacier forelands are ruled by mechanisms of directional species accumulation and
trait selection that involve a trade-off between different functional strategies.
Functional traits that reflect the dispersal and adaptation capability of the
species underpin the colonization success of soil-dwelling lichens in glacier
forelands.
PMID- 28701809
TI - Yield gap analyses to estimate attainable bovine milk yields and evaluate options
to increase production in Ethiopia and India.
AB - Livestock provides an important source of income and nourishment for around one
billion rural households worldwide. Demand for livestock food products is
increasing, especially in developing countries, and there are opportunities to
increase production to meet local demand and increase farm incomes. Estimating
the scale of livestock yield gaps and better understanding factors limiting
current production will help to define the technological and investment needs in
each livestock sector. The aim of this paper is to quantify livestock yield gaps
and evaluate opportunities to increase dairy production in Sub-Saharan Africa and
South Asia, using case studies from Ethiopia and India. We combined three
different methods in our approach. Benchmarking and a frontier analysis were used
to estimate attainable milk yields based on survey data. Household modelling was
then used to simulate the effects of various interventions on dairy production
and income. We tested interventions based on improved livestock nutrition and
genetics in the extensive lowland grazing zone and highland mixed crop-livestock
zones of Ethiopia, and the intensive irrigated and rainfed zones of India. Our
analyses indicate that there are considerable yield gaps for dairy production in
both countries, and opportunities to increase production using the interventions
tested. In some cases, combined interventions could increase production past
currently attainable livestock yields.
PMID- 28701810
TI - Next generation agricultural system models and knowledge products: Synthesis and
strategy.
AB - The purpose of this Special Issue of Agricultural Systems is to lay the
foundation for the next generation of agricultural systems data, models and
knowledge products. In the Introduction to this Special Issue, we described a
vision for accelerating the rate of agricultural innovation and meeting the
growing global need for food and fiber. In this concluding article of the NextGen
Special Issue we synthesize insights and formulate a strategy to advance data,
models, and knowledge products that are consistent with this vision. This
strategy is designed to facilitate a transition from the current, primarily
supply-driven approach toward a more demand-driven approach that would address
key Use Cases where better data, models and knowledge products are seen by end
users as essential to meet their needs.
PMID- 28701811
TI - Next generation agricultural system data, models and knowledge products:
Introduction.
AB - Agricultural system models have become important tools to provide predictive and
assessment capability to a growing array of decision-makers in the private and
public sectors. Despite ongoing research and model improvements, many of the
agricultural models today are direct descendants of research investments
initially made 30-40 years ago, and many of the major advances in data,
information and communication technology (ICT) of the past decade have not been
fully exploited. The purpose of this Special Issue of Agricultural Systems is to
lay the foundation for the next generation of agricultural systems data, models
and knowledge products. The Special Issue is based on a "NextGen" study led by
the Agricultural Model Intercomparison and Improvement Project (AgMIP) with
support from the Bill and Melinda Gates Foundation.
PMID- 28701812
TI - Next generation data systems and knowledge products to support agricultural
producers and science-based policy decision making.
AB - Research on next generation agricultural systems models shows that the most
important current limitation is data, both for on-farm decision support and for
research investment and policy decision making. One of the greatest data
challenges is to obtain reliable data on farm management decision making, both
for current conditions and under scenarios of changed bio-physical and socio
economic conditions. This paper presents a framework for the use of farm-level
and landscape-scale models and data to provide analysis that could be used in
NextGen knowledge products, such as mobile applications or personal computer data
analysis and visualization software. We describe two analytical tools - AgBiz
Logic and TOA-MD - that demonstrate the current capability of farmlevel and
landscape-scale models. The use of these tools is explored with a case study of
an oilseed crop, Camelina sativa, which could be used to produce jet aviation
fuel. We conclude with a discussion of innovations needed to facilitate the use
of farm and policy-level models to generate data and analysis for improved
knowledge products.
PMID- 28701813
TI - Towards a new generation of agricultural system data, models and knowledge
products: Information and communication technology.
AB - Agricultural modeling has long suffered from fragmentation in model
implementation. Many models are developed, there is much redundancy, models are
often poorly coupled, model component re-use is rare, and it is frequently
difficult to apply models to generate real solutions for the agricultural sector.
To improve this situation, we argue that an open, self-sustained, and committed
community is required to co-develop agricultural models and associated data and
tools as a common resource. Such a community can benefit from recent developments
in information and communications technology (ICT). We examine how such
developments can be leveraged to design and implement the next generation of
data, models, and decision support tools for agricultural production systems. Our
objective is to assess relevant technologies for their maturity, expected
development, and potential to benefit the agricultural modeling community. The
technologies considered encompass methods for collaborative development and for
involving stakeholders and users in development in a transdisciplinary manner.
Our qualitative evaluation suggests that as an overall research challenge, the
interoperability of data sources, modular granular open models, reference data
sets for applications and specific user requirements analysis methodologies need
to be addressed to allow agricultural modeling to enter in the big data era. This
will enable much higher analytical capacities and the integrated use of new data
sources. Overall agricultural systems modeling needs to rapidly adopt and absorb
state-of-the-art data and ICT technologies with a focus on the needs of
beneficiaries and on facilitating those who develop applications of their models.
This adoption requires the widespread uptake of a set of best practices as
standard operating procedures.
PMID- 28701814
TI - Modelling the impacts of pests and diseases on agricultural systems.
AB - The improvement and application of pest and disease models to analyse and predict
yield losses including those due to climate change is still a challenge for the
scientific community. Applied modelling of crop diseases and pests has mostly
targeted the development of support capabilities to schedule scouting or
pesticide applications. There is a need for research to both broaden the scope
and evaluate the capabilities of pest and disease models. Key research questions
not only involve the assessment of the potential effects of climate change on
known pathosystems, but also on new pathogens which could alter the (still
incompletely documented) impacts of pests and diseases on agricultural systems.
Yield loss data collected in various current environments may no longer represent
a adequate reference to develop tactical, decision-oriented, models for plant
diseases and pests and their impacts, because of the ongoing changes in climate
patterns. Process-based agricultural simulation modelling, on the other hand,
appears to represent a viable methodology to estimate the impacts of these
potential effects. A new generation of tools based on state-of-the-art knowledge
and technologies is needed to allow systems analysis including key processes and
their dynamics over appropriate suitable range of environmental variables. This
paper offers a brief overview of the current state of development in coupling
pest and disease models to crop models, and discusses technical and scientific
challenges. We propose a five-stage roadmap to improve the simulation of the
impacts caused by plant diseases and pests; i) improve the quality and
availability of data for model inputs; ii) improve the quality and availability
of data for model evaluation; iii) improve the integration with crop models; iv)
improve the processes for model evaluation; and v) develop a community of plant
pest and disease modelers.
PMID- 28701815
TI - Next generation crop models: A modular approach to model early vegetative and
reproductive development of the common bean (Phaseolus vulgaris L).
AB - The next generation of gene-based crop models offers the potential of predicting
crop vegetative and reproductive development based on genotype and weather data
as inputs. Here, we illustrate an approach for developing a dynamic modular gene
based model to simulate changes in main stem node numbers, time to first
anthesis, and final node number on the main stem of common bean (Phaseolus
vulgaris L.). In the modules, these crop characteristics are functions of
relevant genes (quantitative trait loci (QTL)), the environment (E), and QTL * E
interactions. The model was based on data from 187 recombinant inbred (RI)
genotypes and the two parents grown at five sites (Citra, FL; Palmira, Colombia;
Popayan, Colombia; Isabela Puerto Rico; and Prosper, North Dakota). The model
consists of three dynamic QTL effect models for node addition rate (NAR, No. d-
1), daily rate of progress from emergence toward flowering (RF), and daily
maximum main stem node number (MSNODmax), that were integrated to simulate main
stem node number vs. time, and date of first flower using daily time steps. Model
evaluation with genotypes not used in model development showed reliable
predictions across all sites for time to first anthesis (R2 = 0.75) and main stem
node numbers during the linear phase of node addition (R2 = 0.93), while
prediction of the final main stem node number was less reliable (R2 = 0.27). The
use of mixed-effects models to analyze multi-environment data from a wide range
of genotypes holds considerable promise for assisting development of dynamic QTL
effect models capable of simulating vegetative and reproductive development.
PMID- 28701816
TI - Brief history of agricultural systems modeling.
AB - Agricultural systems science generates knowledge that allows researchers to
consider complex problems or take informed agricultural decisions. The rich
history of this science exemplifies the diversity of systems and scales over
which they operate and have been studied. Modeling, an essential tool in
agricultural systems science, has been accomplished by scientists from a wide
range of disciplines, who have contributed concepts and tools over more than six
decades. As agricultural scientists now consider the "next generation" models,
data, and knowledge products needed to meet the increasingly complex systems
problems faced by society, it is important to take stock of this history and its
lessons to ensure that we avoid re-invention and strive to consider all
dimensions of associated challenges. To this end, we summarize here the history
of agricultural systems modeling and identify lessons learned that can help guide
the design and development of next generation of agricultural system tools and
methods. A number of past events combined with overall technological progress in
other fields have strongly contributed to the evolution of agricultural system
modeling, including development of process-based bio-physical models of crops and
livestock, statistical models based on historical observations, and economic
optimization and simulation models at household and regional to global scales.
Characteristics of agricultural systems models have varied widely depending on
the systems involved, their scales, and the wide range of purposes that motivated
their development and use by researchers in different disciplines. Recent trends
in broader collaboration across institutions, across disciplines, and between the
public and private sectors suggest that the stage is set for the major advances
in agricultural systems science that are needed for the next generation of
models, databases, knowledge products and decision support systems. The lessons
from history should be considered to help avoid roadblocks and pitfalls as the
community develops this next generation of agricultural systems models.
PMID- 28701817
TI - Towards a new generation of agricultural system data, models and knowledge
products: Design and improvement.
AB - This paper presents ideas for a new generation of agricultural system models that
could meet the needs of a growing community of end-users exemplified by a set of
Use Cases. We envision new data, models and knowledge products that could
accelerate the innovation process that is needed to achieve the goal of achieving
sustainable local, regional and global food security. We identify desirable
features for models, and describe some of the potential advances that we envisage
for model components and their integration. We propose an implementation strategy
that would link a "pre-competitive" space for model development to a "competitive
space" for knowledge product development and through private-public partnerships
for new data infrastructure. Specific model improvements would be based on
further testing and evaluation of existing models, the development and testing of
modular model components and integration, and linkages of model integration
platforms to new data management and visualization tools.
PMID- 28701818
TI - Toward a new generation of agricultural system data, models, and knowledge
products: State of agricultural systems science.
AB - We review the current state of agricultural systems science, focusing in
particular on the capabilities and limitations of agricultural systems models. We
discuss the state of models relative to five different Use Cases spanning field,
farm, landscape, regional, and global spatial scales and engaging questions in
past, current, and future time periods. Contributions from multiple disciplines
have made major advances relevant to a wide range of agricultural system model
applications at various spatial and temporal scales. Although current
agricultural systems models have features that are needed for the Use Cases, we
found that all of them have limitations and need to be improved. We identified
common limitations across all Use Cases, namely 1) a scarcity of data for
developing, evaluating, and applying agricultural system models and 2) inadequate
knowledge systems that effectively communicate model results to society. We argue
that these limitations are greater obstacles to progress than gaps in conceptual
theory or available methods for using system models. New initiatives on open data
show promise for addressing the data problem, but there also needs to be a
cultural change among agricultural researchers to ensure that data for addressing
the range of Use Cases are available for future model improvements and
applications. We conclude that multiple platforms and multiple models are needed
for model applications for different purposes. The Use Cases provide a useful
framework for considering capabilities and limitations of existing models and
data.
PMID- 28701819
TI - Mercury bioaccumulation increases with latitude in a coastal marine fish
(Atlantic silverside, Menidia menidia).
AB - Human exposure to the neurotoxic methylmercury (MeHg) occurs primarily via the
consumption of marine fish, but the processes underlying large-scale spatial
variations in fish MeHg concentrations [MeHg], which influence human exposure,
are not sufficiently understood. We used the Atlantic silverside (Menidia
menidia), an extensively studied model species and important forage fish, to
examine latitudinal patterns in total Hg [Hg] and [MeHg]. Both [Hg] and [MeHg]
significantly increased with latitude (0.014 and 0.048 MUg MeHg g-1 dw per degree
of latitude in juveniles and adults, respectively). Four known latitudinal trends
in silverside traits help explain these patterns: latitudinal increase in MeHg
assimilation efficiency, latitudinal decrease in MeHg efflux, latitudinal
increase in weight loss due to longer and more severe winters, and latitudinal
increase in food consumption as an adaptation to decreasing length of the growing
season. Given the absence of a latitudinal pattern in particulate MeHg, a diet
proxy for zooplanktivorous fish, we conclude that large-scale spatial variation
in growth is the primary control of Hg bioaccumulation in this and potentially
other fish species.
PMID- 28701820
TI - Scrutinizing the Emotional Nature of Intuitive Coherence Judgments.
AB - Dual-system models propose that cognitive processing can occur either intuitively
or deliberately. Unlike deliberate decision strategies, intuitive ones are
assumed to have an emotional component attached to the decision process. We
tested if intuitive decisions are indeed accompanied by an emotional response
while deliberate decisions are not. Specifically, we conducted a
psychophysiological study in which participants were instructed to decide either
intuitively or deliberately if three simultaneously presented words were
semantically coherent or incoherent (triad task). The degree of emotionality of
these two decision strategies (intuitive vs. deliberate) was compared using
changes in electrodermal activity (EDA) and the reaction time (RT) effect of an
affective priming paradigm as primary measurements. Based on a valence-arousal
model, our results revealed that intuitive and deliberate judgments do not differ
as to their emotional valence but that they do differ in emotional arousal. Most
notably, sympathetic activation during intuitive judgments was significantly
lower compared to sympathetic activation during deliberate judgments. Our results
reflect that a relaxed state of mind-manifested in low sympathetic activity-could
underlie the holistic processing that is assumed to facilitate the proliferation
of semantic associations during coherence judgments. This suggests that coherence
judgments made under an (instructed) intuitive decision mode have a specific
psychophysiological signature and that arousal is the differentiating component
between intuitive and deliberate decision strategies.
PMID- 28701821
TI - An Exploratory Study of Intensive Neurofeedback Training for Schizophrenia.
AB - Schizophrenia is a chronic and devastating brain disorder with ongoing cognitive,
behavioral, and emotional deteriorated functions. Neurofeedback training, which
enables the individuals to regulate their brain activity using a real-time
feedback loop, is increasingly investigated as a potential alternative
intervention for schizophrenia. This study aimed to explore the effect of short
but intensive neurofeedback training for schizophrenic patients with difficulty
for long-time training. A middle-aged woman with chronic schizophrenia completed
the intensive training of alpha/beta2 (20-30 Hz) in four consecutive days with a
total training duration of 13.5 hours. The results showed that her alpha/beta2
increased over sessions, and her behavior performance including short-term
memory, mood, and speech pattern was improved at the end of neurofeedback
training. Importantly, a 22-month follow-up found a dramatic improvement in both
positive and negative symptoms. These positive outcomes suggest that such
intensive neurofeedback training may provide new insight into the treatment of
schizophrenia and thus deserves further study to fully examine its scope.
PMID- 28701822
TI - The Difference of Neural Networks between Bimanual Antiphase and In-Phase Upper
Limb Movements: A Preliminary Functional Magnetic Resonance Imaging Study.
AB - Most daily movements require some degree of collaboration between the upper
limbs. The neural mechanisms are bimanual-condition specific and therefore should
be different between different activities. In this study, we aimed to explore
intraregional activation and interregional connectivity during bimanual movement
by functional magnetic resonance imaging (fMRI). Ten right-handed, normal
subjects were recruited. The neural correlates of unimanual (right side) and
bimanual (in-phase and antiphase) upper limb movements were investigated.
Connectivity analyses were carried out using the psychophysiological interaction
(PPI) model. The cerebellum was strongly activated in both unimanual and bimanual
movements, and the cingulate motor area (CMA) was the most activated brain area
in antiphase bimanual movement. Moreover, compared with unimanual movement, CMA
activation was also observed in antiphase bimanual movement, but not in in-phase
bimanual movement. In addition, we carried out the PPI model to study the
differences of effective connectivity and found that the cerebellum was more
connected with the CMA during antiphase bimanual movement than in-phase bimanual
movement. Our findings elucidate the differences of the cerebellar-cerebral
functional connectivity between antiphase and in-phase bimanual movements, which
could be used to facilitate the development of a neuroscience perspective on
bimanual movement control in patients with motor impairments.
PMID- 28701823
TI - Innovative technologies to manage aflatoxins in foods and feeds and the
profitability of application - A review.
AB - Aflatoxins are mainly produced by certain strains of Aspergillus flavus, which
are found in diverse agricultural crops. In many lower-income countries,
aflatoxins pose serious public health issues since the occurrence of these toxins
can be considerably common and even extreme. Aflatoxins can negatively affect
health of livestock and poultry due to contaminated feeds. Additionally, they
significantly limit the development of international trade as a result of strict
regulation in high-value markets. Due to their high stability, aflatoxins are not
only a problem during cropping, but also during storage, transport, processing,
and handling steps. Consequently, innovative evidence-based technologies are
urgently required to minimize aflatoxin exposure. Thus far, biological control
has been developed as the most innovative potential technology of controlling
aflatoxin contamination in crops, which uses competitive exclusion of toxigenic
strains by non-toxigenic ones. This technology is commercially applied in
groundnuts maize, cottonseed, and pistachios during pre-harvest stages. Some
other effective technologies such as irradiation, ozone fumigation, chemical and
biological control agents, and improved packaging materials can also minimize
post-harvest aflatoxins contamination in agricultural products. However,
integrated adoption of these pre- and post-harvest technologies is still required
for sustainable solutions to reduce aflatoxins contamination, which enhances food
security, alleviates malnutrition, and strengthens economic sustainability.
PMID- 28701824
TI - Liquid-based and conventional cytology for bronchial washings/bronchoalveolar
lavages in the diagnosis of malignancy - An institutional experience.
AB - BACKGROUND: Liquid-based cytology (LBC) has been developed as an alternative for
conventional cytology (CC) in cervical smears. It is now increasingly being used
all over the world for cervical cancer screening. However, its role and
diagnostic accuracy in bronchial wash (BW)/bronchoalveolar lavage (BAL) specimens
remains undetermined. AIMS: To assess and compare the diagnostic performance and
accuracy of LBC with CC for detecting malignancy in bronchial specimens. SETTINGS
AND DESIGN: This was a retrospective analytical hospital-based study. MATERIALS
AND METHODS: Bronchial specimens (BW/BAL) received over a period of 4.5 years
were reviewed. The samples were processed by CC from June 2010 to September 2012
(2.25 years) and by LBC from October 2012 to December 2014 (2.25 years). Data
were retrieved from the records of cytology laboratory and compared among both
the groups. Detection rate for histologically or cytologically verified samples
was calculated. RESULTS: A total of 559 cases verified by histological and
cytological follow-up were evaluated. These included 247 CC cases and 312 LBC
cases. The positive diagnostic rate for malignancy in CC was 28.6% whereas that
for LBC was 32.9%. The negative diagnostic rates were 66.5% and 66.3% for CC and
LBC, respectively. However, unsatisfactory rates had shown a good reduction from
4.4% in CC to 0.6% after LBC introduction. The smears showed more homogeneous
distribution of cells with elimination of obscuring factors such as blood,
inflammation, and mucus. CONCLUSIONS: The diagnostic accuracy of LBC was slightly
better than CC. The unsatisfactory rates showed reduction in LBC preparation.
Thus, LBC is a viable alternative to CC and has the advantages of standardization
of preparation with decrease in unsatisfactory rates.
PMID- 28701825
TI - Role of cell block in cytopathologic evaluation of image-guided fine needle
aspiration cytology.
AB - CONTEXT: Fine needle aspiration cytology (FNAC) of superficial or deep-seated
lesion is an increasingly common practice, eliminating time consuming and costly
diagnostic procedures and providing rapid and safe diagnosis. AIMS: To assess
utility of cell block preparation method in increasing sensitivity of
cytodiagnosis in deep-seated image-guided FNACs. SETTINGS AND DESIGN: This was a
hospital-based observational study conducted in the Department of Pathology, over
a period of one and a half years. MATERIALS AND METHODS: A total of 46 cases of
abdomino-pelvic and intrathoracic masses subjected to guided FNACs were included.
Along with conventional smears, cell blocks were prepared by using AAF (95%
Ethanol 34 ml + formalin 4 ml + Glacial acetic acid 2 ml) as fixative agent.
STATISTICAL ANALYSIS USED: Done using MedCalc Version 12.7.5.0 to find out the
sensitivity, specificity, and diagnostic accuracy of conventional smears and cell
blocks. RESULTS: The sensitivity, specificity, and diagnostic accuracy of cell
blocks in our study was 71.11%, 100%, and 71.73%, respectively. The figures for
FNA smears were 62.22%, 100%, and 63.04%, respectively. CONCLUSIONS: Cell block
technique by AAF fixative is a simple, inexpensive procedure. Cell block method
allows the recovery and processing of minute amounts of cellular material,
facilitating better classification of tumor when reviewed along with cytological
smears, the ability to obtain many sections for immunostains and other studies to
be performed akin to paraffin sections produced in histopathology.
PMID- 28701826
TI - Cytomorphological patterns of tubercular lymphadenitis and its comparison with
Ziehl-Neelsen staining and culture in eastern up. (Gorakhpur region): Cytological
study of 400 cases.
AB - BACKGROUND: Tuberculous lymphadenitis is most common cause of lymphadenopathy in
developing countries. Although enormous literature is available on various
aspects of the disease including cytological patterns and its incidence in others
parts of India and in other countries, only limited literature is available
regarding its incidence and morphological spectrum on cytology in eastern parts
of Uttar Pradesh in Gorakhpur region. AIM: The present study was undertaken to
estimate the incidence of tuberculous lymphadenitis in our settings along with
its morphological spectrum on cytology as well as to determine the utility of
culture of fine needle aspirates in addition to cytology and Ziehl-Neelsen (ZN)
staining. MATERIAL AND METHODS: Four hundred cases of superficial lymphadenopathy
were subjected to fine needle aspiration cytology (FNAC), and in case, smears
were stained with Hematoxylin and eosin (H and E), Giemsa, and ZN stain and
categorized into three cytomorphological patterns. All the aspirates were
inoculated on two sterile Lowenstein Jensen (LJ) medium. RESULT: Out of 400 cases
of consecutive lymph nodes aspirated, 180 cases (45%) showed features of
tuberculous lymphadenitis. Smears revealed epithelioid granulomas with caseous
necrosis in maximum cases (40%). On statistical analysis, difference between
group I and group II was found to be significant (P < 0.05); while comparison
between groups II and III as well as between groups I and III was found to be
statistically insignificant. Overall, acid fast bacilli positivity was seen in
51.6% of the cases. CONCLUSION: FNAC has been proved very safe, highly sensitive,
and first line investigation in diagnosing tubercular lymphadenitis. The
sensitivity can be further be increased by complementary cytomorphology with acid
fast staining. Diagnostic accuracy can further be increased by culture.
PMID- 28701827
TI - Malignancy rate in thyroid nodules categorized as atypia of undetermined
significance or follicular lesion of undetermined significance - An institutional
experience.
AB - INTRODUCTION: Atypia of undetermined significance (AUS) or follicular lesion of
undetermined significance (FLUS) of Bethesda system for reporting thyroid
cytopathology has emerged as most controversial category due to its heterogeneity
and inconsistent usage. Initially associated risk of malignancy was estimated to
be about 5-15%, but eventually different results have been obtained across
institutions due to variable follow-ups and interpretation. The present study was
conducted to evaluate the rate of malignancy along with appropriate management in
this category. MATERIALS AND METHODS: The study included AUS/FLUS cases diagnosed
over period of 4 years on thyroid fine needle aspiration cytology (FNAC).
Detailed clinical history and radiological examination were recorded along with
follow-ups and management of all cases. Histopathology was available for cases
which underwent surgery due to high clinical suspicion, worrisome radiological
features or two consecutive AUS/FLUS reports. RESULTS: The incidence of AUS/FLUS
was 6.4% with repeat FNAC done in 39.6%, immediate surgery in 49.2% and follow-up
without intervention in 11.1% cases. The overall malignancy rate was 28.5% with
most common malignancy being follicular variant of papillary carcinoma (FVPC).
Malignancy rate was more in cases (24.1%) which morphologically showed atypical
nuclear features in comparison to architectural atypia. CONCLUSION: AUS/FLUS is
associated with higher risk of malignancy than previously anticipated. Surgical
intervention may have greater implication than repeat FNAC in appropriate
management of this category. Substratification of this category according to
nuclear features and architecture may be more useful in predicting malignancy
risk and reducing the variability in the group.
PMID- 28701828
TI - Modified ultrafast Papanicolaou staining technique: A comparative study.
AB - INTRODUCTION: Ultrafast Papanicolaou stain (UFP) was introduced as a hybrid of
Romanowsky and Papanicolaou (PAP) stain. It enhances the quality and reduces the
time. In the present study, a modified staining technique was adapted where
Gill's Hematoxylin was replaced by Harris Hematoxylin. AIMS: The aim of the study
was to assess the use of the modified ultrafast Papanicolaou (MUFP) stain for
fine needle aspiration cytology (FNAC) of head and neck swellings in comparison
with the routine PAP stain, hematoxylin and eosin (H and E), and Giemsa.
MATERIALS AND METHODS: Forty FNACs of head and neck swellings were collected.
FNAC procedure was performed by standard method; two smears were fixed in 95%
propanol and stained with PAP and H and E. Two smears were air dried, 1 was
stained with Giemsa, and 1 was rehydrated with normal saline, fixed in alcoholic
formalin, and stained with MUFP. Four parameters were considered and scored
background, cell morphology, nuclear staining, and overall staining pattern).
RESULTS: The quality of MUFP smears were better when compared to routine PAP, H
and E, and Giemsa, and was statistically significant by Wilcoxon matched pair
test. CONCLUSIONS: MUFP stain in comparison to routine PAP, H and E, and Giemsa
provides an excellent and suitable alterative in cytological staining for the
study of various organs.
PMID- 28701829
TI - Warthin-Finkeldy cells - A soft indicator in cytodiagnosis of Kimura.
PMID- 28701830
TI - Role of fine-needle aspiration cytology in diagnosis of disseminated
histoplasmosis in an immunocompetent patient: A case report.
AB - Histoplasmosis is a mycotic infection caused by dimorphic fungus, Histoplasma
capsulatum. The organisms are usually found within the cells (macrophages). This
organism mostly affects lungs in immunocompetent individuals and disseminated
forms are seen in immunocompromised cases. Here, we describe a case of
disseminated histoplasmosis in an immunocompetent, 35-year-old female with
lymphadenopathy diagnosed by fine-needle aspiration cytology and cell block.
PMID- 28701831
TI - Intestinal GIST masquerading as an ovarian mass: Diagnosed on FNAC.
AB - The preoperative diagnosis of metastatic intestinal gastrointestinal stromal
tumors (GIST) on cytology can be quite difficult at times. The present case
characterizes the cytomorphological and immunocytochemical features of GIST,
emphasizing the utility of fine-needle aspiration cytology (FNAC) in the
evaluation of spindle cell tumors of gastrointestinal tract. An accurate and
early diagnosis of GIST affects the treatment, primarily allowing the use of
tyrosine kinase inhibitors in unresectable or metastatic cases. Presence of
highly cellular fragments of spindle-to-oval cells with variable degree of
pleomorphism, atypia, and necrosis supplemented by immunocytochemistry can render
a cytological diagnosis of GIST in dilemmatic clinical situations. Our case
highlights the diagnostic role of FNAC in the evaluation of a pelvic mass, which
was clinicoradiologically misdiagnosed as ovarian carcinoma.
PMID- 28701832
TI - Tuberculous mastitis diagnosed on cytology - case report of a rare entity.
AB - Tuberculous mastititis is a rare clinical entity and usually affects women from
the Indian subcontinent. It often mimics breast carcinoma and pyogenic breast
abscess. Fine needle aspiration cytology (FNAC) is a very essential diagnostic
tool when other routine laboratory investigations are not helpful in reaching to
the conclusion. Tuberculosis (TB) of the breast is an uncommon presentation of TB
even in countries where the incidence of pulmonary and extrapulmonary TB is high.
Radiological imaging is not diagnostic.
PMID- 28701833
TI - Anaplastic large cell lymphoma: A great mimic on cytology.
AB - Anaplastic large cell lymphoma (ALCL) is a T-cell lymphoma, accounting for <5% of
non-Hodgkin's lymphoma. Cutaneous involvement can be primary or secondary arising
in systemic ALCL. The diagnostic feature in both is the presence of pleomorphic,
CD30 positive hallmark cells. We present a case of ALCL in a 19-year-old male
presenting as an ulcerated scalp swelling. Clinical impression was actinomycosis
or scrofuloderma. Cytology smears showed large dispersed pleomorphic cells with
hyperlobated nuclei and multinucleated giant cells. The differentials considered
were ALCL, rhabdomyosarcoma, and poorly differentiated carcinoma.
Immunocytochemistry (ICC) showed positivity for leukocyte common antigen (LCA)
and CD30 while negativity for desmin, favoring ALCL. Computed tomography (CT)
showed a lytic paravertebral lesion. Subsequently, both paraspinal and scalp
lesions were biopsied and immunochemistry confirmed the diagnosis of ALCL. Thus,
cutaneous involvement in ALCL can resemble inflammatory and other neoplastic
lesions clinically and cytologically. Hence, a high index of suspicion and ICC
can aid in the correct diagnosis on fine needle aspiration cytology (FNAC).
PMID- 28701834
TI - Ceruminous adenoma: A rare tumor diagnosed on cytology with histological
correlation.
AB - Ceruminous adenoma (CA) is a rare, benign tumor of the ceruminous gland found in
the cartilaginous part of the external auditory canal (EAC). The tumor is
diagnosed on histopathology and shows a characteristic dual population of luminal
epithelial cells and basal myoepithelial cells. However, CA can be diagnosed on
fine-needle aspiration cytology (FNAC) prior to surgery and the cytopathologist
should be well aware of its cytological findings to avoid any misdiagnosis. The
tumor shows an excellent prognosis with possible recurrence and malignant
transformation. The present case emphasizes the cytological features of CA, which
have been scantily described in the literature and highlights the role of
cytopathologists in preoperative diagnosis.
PMID- 28701835
TI - Sarcoma in urine cytology; an extremely rare entity: A report of two cases.
AB - Primary sarcomas of the urinary bladder or prostate are extremely rare entities.
The rarity and lack of awareness makes it difficult for the cytologists to detect
the spindle cell lesions in urine for malignant cytology. The literature
available for the detection of urinary tract sarcomas is little. Here, we report
the urine cytology findings of two interesting cases of urinary bladder and
prostatic leiomyosarcoma.
PMID- 28701836
TI - Fine needle aspiration cytology diagnosis of metastatic malignant diffuse type
tenosynovial giant cell tumor.
AB - Tenosynovial giant cell tumors (TGCTs) arise from the synovium of joint, bursa,
and tendon sheath, and are classified into localized and diffuse types. Diffused
type often affects the large joint, and has more recurrence, metastasis, and
malignant transformation potential compared to the localized type. Malignant
diffused TGCT (D-TGCT) usually occurs as a large tumor (>5 cm), in older
patients, and its histopathologic features include necrosis, cellular anaplasia,
prominent nucleoli, high nuclear cytoplasmic ratio, brisk mitosis, discohesion of
tumor cells, paucity of giant cells, and a diffuse growth pattern. At least five
of these criteria are required for the histopathologic diagnosis of malignant
TGCT because the benign TGCT also shares many of these morphological features. We
describe the cytomorphologic features of a malignant D-TGCT from an unusual case
of pulmonary metastasis in an adult patient. Fine needle aspiration cytologic
features of malignant D-TGCT have not been described earlier in the English
literature.
PMID- 28701837
TI - Hodgkin's lymphoma masquerading as suppurative lymphadenitis.
PMID- 28701838
TI - A Retrospective Study of Physiological Observation-reporting Practices and the
Recognition, Response, and Outcomes Following Cardiopulmonary Arrest in a Low-to
middle-income Country.
AB - BACKGROUND AND AIMS: In Sri Lanka, as in most low-to-middle-income countries
(LMICs), early warning systems (EWSs) are not in use. Understanding observation
reporting practices and response to deterioration is a necessary step in
evaluating the feasibility of EWS implementation in a LMIC setting. This study
describes the practices of observation reporting and the recognition and response
to presumed cardiopulmonary arrest in a LMIC. PATIENTS AND METHODS: This
retrospective study was carried out at District General Hospital Monaragala, Sri
Lanka. One hundred and fifty adult patients who had cardiac arrests and were
reported to a nurse responder were included in the study. RESULTS: Availability
of six parameters (excluding mentation) was significantly higher at admission (P
< 0.05) than at 24 and 48 h prior to cardiac arrest. Patients had a 49.3%
immediate return of spontaneous circulation (ROSC) and 35.3% survival to hospital
discharge. Nearly 48.6% of patients who had ROSC did not receive postarrest
intensive care. Intubation was performed in 46 (62.2%) patients who went on to
have ROSC compared with 28 (36.8%) with no ROSC (P < 0.05). Defibrillation,
performed in eight (10.8%) patients who had ROSC and eight (10.5%) in whom did
not, was statistically insignificant (P = 0.995). CONCLUSIONS: Observations
commonly used to detect deterioration are poorly reported, and reporting
practices would need to be improved prior to EWS implementation. These findings
reinforce the need for training in acute care and resuscitation skills for health
care teams in LMIC settings as part of a program of improving recognition and
response to acute deterioration.
PMID- 28701839
TI - A Study of Continuous Renal Replacement Therapy and Acute Peritoneal Dialysis in
Hemodynamic Unstable Patients.
AB - OBJECTIVE: The objective of the following study was to assess the outcome of
continuous renal replacement therapy (CRRT) and acute peritoneal dialysis (PD) in
dialysis-requiring renal failure in patients with hemodynamic instability.
MATERIALS AND METHODS: A retrospective analysis of all the patients who received
CRRT and acute PD over a period of 1 year at our institute, a tertiary care
center, was done for diagnosis, type of renal replacement therapy (RRT), and
survival outcome. The indications for administering either of the therapy were
usual indications of doing hemodialysis with the presence of hemodynamic
instability (systolic blood pressure <90 mm of Hg even with inotropes). RESULTS:
Forty patients, 22 in CRRT and 18 in acute PD group were studied. All these
patients required inotropes to maintain desired blood pressure. Twenty-five
(62.5%) patients had acute kidney injury (AKI), and 15 (37.5%) had chronic kidney
disease (CKD) superimposed over other primary diagnosis. A total of 8 (20%)
patients (4 in CRRT, 4 in acute PD) survived at the time of discharge from
hospital. The mean age of survivors was approximately a decade less than
nonsurvivors (P = 0.15). Overall, there were no survivors in CKD group and all
the patients who survived at the time of discharge from hospital had underlying
AKI (P = 0.016). CONCLUSION: This study showing comparable survival outcome in
acute PD and CRRT gives evidence that either of the modalities can be adopted in
hemodynamically unstable patients requiring RRT depending on the resources
available.
PMID- 28701840
TI - Colistin Nephrotoxicity in Adults: Single Centre Large Series from India.
AB - CONTEXT: Limited Indian data are available on the rate of colistin nephrotoxicity
and other risk factors contributing to the development of this important side
effect. AIM: This study aims to generate data on colistin nephrotoxicity from a
large cohort of Indian patients. DESIGN: Retrospective cohort study. MATERIALS
AND METHODS: Case record analysis of patients who received colistin, in an
oncology center in India, between January 2011 and December 2015. Nephrotoxicity
was assessed using risk, injury, failure, loss, and end-stage (RIFLE) criteria.
STATISTICAL ANALYSIS: P < 0.05 was considered as statistically significant.
RESULTS: Out of the 229 patients, 13.1% (30/229) developed abnormal RIFLE.
Abnormal RIFLE group (n = 30), in comparison to the normal renal function group
(n = 199), had higher number of patients in intensive care unit (ICU) (96% vs.
79%, P = 0.02), higher Acute Physiology and Chronic Health Evaluation (APACHE II)
score (23 vs. 19 P = 0.0001), Charlson score (5.9 vs. 4.3, P = 0.001), mechanical
ventilation (90% vs. 67%, P = 0.016), 28 days mortality (63% vs. 25%, P =
0.0001), and abnormal baseline creatinine (36% vs. 8%, P = 0.001).
Coadministration of vancomycin had higher rates of nephrotoxicity (P = 0.039).
There was no significant difference in nephrotoxicity between 6 and 9 MU/day
dosing pattern (8.8% vs. 13.8%, P = 0.058). CONCLUSION: Nephrotoxicity rate in
our retrospective single center large series of patients receiving colistin was
13.1%. Patients with abnormal baseline creatinine, ICU stay, and higher disease
severity are at higher risk of nephrotoxicity while on colistin. A daily dose of
9 million does not significantly increase nephrotoxicity compared to the 6
million. Concomitant administration of vancomycin with colistin increases the
risk of nephrotoxicity.
PMID- 28701841
TI - Continuous Renal Replacement Therapy Applications on Extracorporeal Membrane
Oxygenation Circuit.
AB - BACKGROUND AND AIMS: Continuous venovenous hemofiltration or hemodiafiltration is
used frequently in pediatric patients, but experience of continuous renal
replacement therapy (CRRT) application on extracorporeal membrane oxygenation
(ECMO) circuit is still limited. Among several methods used for applying CRRT on
ECMO patients, we aim to share our experience on inclusion of a CRRT device in
the ECMO circuit which we believe is easier and safer to apply. MATERIALS AND
METHODS: The data were collected on demographics, outcomes, and details of the
treatment of ECMO patients who had CRRT. During the study period of 3 years,
venous cannula of ECMO circuit before pump was used for CRRT access for both the
filter inlet and outlet of CRRT machine to minimize the thromboembolic
complications. The common indication for CRRT was fluid overload. RESULTS: CRRT
was used in 3.68% of a total number of patients admitted and 43% of patients on
ECMO. The patients have undergone renal replacement therapy for periods of time
ranging between 24 h and 25 days (260 h mean). The survival rate of this group of
patients with multiorgan failure was 33%. Renal recovery occurred in all of the
survivors. Complications such as electrolyte imbalance, hypothermia, and
bradykinin syndrome were easily managed. CONCLUSIONS: Adding a CRRT device on
ECMO circuit is a safe and effective technique. The major advantages of this
technique are easy to access, applying CRRT without extra anticoagulation
process, preventing potential hemodynamic disturbances, and increased clearance
of solutes and fluid overload using larger hemofilter.
PMID- 28701842
TI - Quality of Dying in the Medical Intensive Care Unit: Comparison between Thai
Buddhists and Thai Muslims.
AB - BACKGROUND AND AIMS: Religious belief is an important aspect that influences the
life of a patient, especially in Asia. We aim to compare the quality of death in
an Intensive Care Unit (ICU) between Buddhists and Muslims from the perspectives
of the relatives of the patients and the nurses and physicians. SUBJECTS AND
METHODS: This was a cohort study of critically ill patients who died after
admission to a medical ICU in Songklanagarind Hospital in Thailand between 2015
and 2016. We interviewed by telephone the relatives of patients. The nurses and
physicians who cared for the patients responded to a self-questionnaire. RESULTS:
A total of 112 patients were enrolled in the study. The quality of death and
dying-1 scores in Thai Buddhists and Muslim patients rated by the relatives (8
vs. 8, P = 0.55), nurses (8 vs. 8, P = 0.28), and physicians (7 vs. 7, P = 0.74)
were not different. The ratings by the nurses correlated with the relatives (rs =
0.41, P < 0.001) but did not correlate with the physicians (rs = 0.15, P = 0.12).
Compared with Buddhist patients, Muslim patients were more likely to have
documentation in place at the time of the death of do not resuscitate (100% vs.
80.2%, P = 0.02) and withholding and withdrawing life support (100% vs. 80.2%, P
= 0.02). CONCLUSION: There was no difference in the quality of dying and death
between Thai Buddhists and Muslims. However, some elements of palliative care
were not similar.
PMID- 28701843
TI - Incidence Proportion of Acute Cor Pulmonale in Patients with Acute Respiratory
Distress Syndrome Subjected to Lung Protective Ventilation: A Systematic Review
and Meta-analysis.
AB - INTRODUCTION: Reported incidence of acute cor pulmonale (ACP) in patients with
acute respiratory distress syndrome (ARDS) varies from 10% to 84%, despite being
subjected to lung protective ventilation according to the current guidelines. The
objective of this review is to find pooled cumulative incidence of ACP in
patients with ARDS undergoing lung protective ventilation. MATERIALS AND METHODS:
We searched MEDLINE, EMBASE, Cochrane Library, KoreaMed, LILACS, and WHO Clinical
Trial Registry. Cross-sectional or cohort studies were included if they reported
or provided data that could be used to calculate the incidence proportion of ACP.
Inverse variance heterogeneity (IVhet) and random effect model were used for the
main outcome and measures. RESULTS: We included 16 studies encompassing 1661
patients. The cumulative incidence of ACP using IVhet analysis was 23% (95%
confidence interval [CI] = 18%-28%) over 3 days of lung protective ventilation.
Random effect analysis of 7 studies (1250 patients) revealed pooled odd ratio of
mortality of 1.16 (95% CI = 0.80-1.67, P = 0.44) due to ACP. CONCLUSION: Patients
with ARDS have a 23% risk of developing ACP with lung protective ventilation.
Findings of this review indicate the need of updating existing guidelines for
ventilating ARDS patients to incorporate right ventricle protective strategy.
PMID- 28701844
TI - Effect of Calories Delivered on Clinical Outcomes in Critically Ill Patients:
Systemic Review and Meta-analysis.
AB - INTRODUCTION: International guidelines are promoting early enteral nutrition (EN)
as a means of feeding critically ill adult patients to improve clinical outcomes.
The question of how much calorie intake is enough to improve the outcomes still
remained inconclusive. Therefore, we carried out a meta-analysis to evaluate the
effect of low calorie (LC) versus high calorie (HC) delivery on critically ill
patients' outcomes. METHODS: We included randomized clinical trials (RCTs) that
compared LC EN with or without supplemental parenteral nutrition with HC delivery
in this meta-analysis irrespective of the site of nutritional delivery in the
gastrointestinal tract. We searched PubMed, EMBASE, and Cochrane central register
of controlled trials electronic databases to identify RCTs that compared the
effects of initially different calorie intake in critical illness. The primary
outcome was overall mortality. RESULTS: This meta-analysis included 17 RCTs with
a total of 3,593 participants. The result of analysis showed that there was no
significant difference between the LC group and HC group in overall mortality
(risk ratio [RR], 0.98; 95% confidence interval [CI], 0.87-1.10; P = 0.74; I2 =
6%; P = 0.38), or new-onset pneumonia (RR, 0.92; 95% CI, 0.73-1.16, P = 0.46; I2
= 38%, P = 0. 11). CONCLUSION: The current meta-analysis showed that there was no
significant difference in mortality of critically ill patients initially between
the two groups.
PMID- 28701845
TI - Fatal Postoperative Hemolysis Due to Severe Falciparum Malaria.
AB - A 60-year-old apparently healthy female patient underwent mastectomy for breast
cancer. She had sinus tachycardia and no other abnormal finding in the
preoperative period. However, the immediate postoperative course was stormy with
the development of anemia, thrombocytopenia, hemolysis, and renal failure with
severe metabolic acidosis. Peripheral blood smear revealed the presence of ring
forms of Plasmodium falciparum. Multiorgan failure and death occurred within 36 h
of surgery in spite of initiation of antimalarial agents. Diagnosis of malaria
should be kept in mind in the event of development of sudden unexplained
deterioration or multiorgan dysfunction associated with thrombocytopenia,
hemolysis, and severe metabolic acidosis, even in previously asymptomatic
patients, especially in residents or recent travelers of the malaria-endemic
area.
PMID- 28701846
TI - Rare Presentation of Congenital Diaphragmatic Hernia in a Sexagenarian.
AB - Congenital diaphragmatic hernia (CDH) usually presents in the neonatal period,
and about 10% of reported cases occur in adults. The most common type is
Bochdalek's hernia, which occurs through a defect in the posterolateral portion
of the diaphragm with an estimated prevalence of 1 in 2500 live births. CDH in
adults presents with gastrointestinal or respiratory symptoms, which can be acute
or intermittent. We report a case of CDH diagnosed in a 55-year-old man, who
presented with acute onset of chest pain and dyspnea with insignificant past
history. This patient was initially evaluated medically for myocardial infarction
followed by intercostal chest drainage placement, before a definitive diagnosis
of CDH was made. This case is reported for its rarity and to highlight the high
index of suspicion needed to diagnose CDH in adulthood. This is specially
important as CDH, masquerades as other acute conditions in older individuals
thereby delaying the diagnosis.
PMID- 28701847
TI - Melioidosis: An Emerging Infection with Fatal Outcomes.
AB - According to the Centers for Disease Control and Prevention, from being
nonendemic for melioidosis, India has now become endemic for the disease since
2012. Until then, melioidosis cases were being reported sporadically from India.
There have been isolated case reports from few states across the country for the
past few years. Most of the times, Burkholderia pseudomallei may be misreported
as Pseudomonas species, especially in resource-poor laboratories. Due to its
varied clinical presentation, the specific clinical diagnosis can be difficult,
thereby making laboratory diagnosis mandatory. This could make a huge impact on
patient care as this organism has a different treatment protocol as well as
virulence determinants which influence the course of management. Although known
for its endemicity in Australia, Thailand, and other Southeast Asian countries,
B. pseudomallei has emerged in new areas such as India, Southern China, Brazil,
and Malawi. We present a rare case of melioidosis with rapid disease progression
to fatal outcome from Chennai, South India.
PMID- 28701848
TI - Metatarsal Fracture Leading to Massive Pulmonary Embolism.
AB - Immobilization and bed rest after fracture and orthopedic surgery are routinely
advised protocol. Period of bed rest usually depends on the type of injury and
orthopedic procedure, ranging from few days to weeks. The trauma, surgery, and
immobilization with other contributing factors can lead to deep vein thrombosis
and pulmonary embolism (PE) in these patients. Although there is high incidence
of PE in such patients, it is difficult to diagnose, primarily because of the
variety of nonspecific signs and symptoms. Here, we discuss a case of a 30-year
old female, who had suffered a trivial roadside accident leading to metatarsal
bone fracture and later on presented in emergency with seizures, pulmonary edema,
and cardiac arrest, after immobilization of just 5 days which was diagnosed to be
result of massive PE. Here, we will discuss the pathophysiology, risk factors,
and management of massive PE.
PMID- 28701849
TI - Blunt Trauma Neck with Complete Tracheal Transection - A Diagnostic and
Therapeutic Challenge to the Trauma Team.
AB - Survival following trachea-esophageal transection is uncommon. Establishing a
secure airway has the highest priority in trauma management. Airway management is
a unique and a defining element to the specialty of emergency medicine. There is
no doubt regarding the significance of establishing a patent airway in the
critically ill patient in the emergency department. Cannot intubate and cannot
ventilate situation is a nightmare to all emergency physicians. The most
important take-home message from this case report is that every Emergency
physician should have the ability to predict "difficult airway" and recognize
"failed airway" very early and be skilled in performing rescue techniques when
routine oral-tracheal intubation fails. Any delay at any step in the "failed
airway" management algorithm may not save the critically ill dying patient. Here,
we report a case of blunt trauma following high-velocity road traffic accident,
presenting in the peri-arrest state, in whom we noticed "failed airway" which
turned out to be due to complete tracheal transection. In our patient, although
we had secured the airway immediately, he had already sustained hypoxic brain
damage. This scenario emphasizes the importance of prehospital care in developing
countries.
PMID- 28701850
TI - Invasive Mediastinal Aspergillosis in Immunocompetent Male with Invasion of Left
Atrium and Hilar Structures.
AB - Aspergillus is described as mould characterised by septate hyphae about 2-4MU in
diameter, it is ubiquitous in nature and spreads by inhalation of spores. It
causes opportunistic infections in almost six forms namely Allergic
bronchopulmonary aspergillosis, Aspergillus sinusitis, Cutaneous aspergillosis,
Aspergilloma, Chronic pulmonary aspergillosis, Invasive aspergillosis. Invasive
aspergillosis of mediastinum in an immunocompetent patient has rarely been
reported. We present a case of a young male who had presented with chest pain,
cough and breathleness was later diagnosed as fulminant mediastinal
aspergillosis. Incisional biopsy with histology report and endotracheal cultures
helped in diagnosing mediastinal aspergillosis. Despite initiation of the right
antifungal therapy and best supportive measures, patient died of septic shock and
multiorgan dysfunction. This case report highlights the need for higher suspicion
in such cases of mediastinal masses and early tissue biopsy which can help in
reducing mortality.
PMID- 28701851
TI - Awareness of Allergic Angina Syndrome.
PMID- 28701852
TI - Encouraging treatment algorithm for computer-assisted navigated total knee
arthroplasty (TKA): A retrospective cohort analysis.
AB - OBJECTIVE: Navigated computer-assisted total knee arthroplasty (TKA) shows
inconclusive mid- to long-term outcome results and is limited by increased costs,
surgery-time and an additional learning curve. We introduced a treatment
algorithm preserving computer-assisted TKA for patients with adipositas-per
magna, posttraumatic leg-deformities, osteosynthetic material in-situ or reduced
preoperative X-ray quality. METHODS: 237 primary unilateral TKA were allocated
based on the treatment concept described above. A retrospective pre- and
postoperative radiological analysis was performed. RESULTS: 222 TKA (93.7%) were
within 3 degrees varus/valgus of mechanical-lower-limb axis (mean absolute
deviation: 1.8 degrees +/- 1.3 degrees ). CONCLUSION: This algorithm showed an
excellent postoperative implantation-accuracy based on an accurate preoperative
surgery-planning.
PMID- 28701853
TI - Low incidence of failure after proximal biceps tenodesis with unicortical suture
button.
AB - PURPOSE: Recent interest in suture button fixation has developed with regard to
proximal biceps tenodesis fixation. Biomechanical studies have demonstrated
viability of a unicortical suture button technique in vitro. Despite this, no
clinical data has been reported to validate the biomechanical data. The purpose
of this study is to report on complication and failure rates in the early
postoperative period after bicep tenodesis with a unicortical suture button.
METHODS: A retrospective review was performed of all biceps tenodesis performed
at our institution over a 36-month period using a unicortical suture button for
fixation. All included patients had a minimum 12 weeks follow up. Failures were
defined as complete loss of fixation, change in biceps contour during the early
postoperative period, acute pain at the tenodesis site, or acute loss of
supination strength. RESULTS: 145 of 166 biceps tenodesis procedures performed by
the 4 surgeons at our institution met inclusion criteria. 80.1% of the patients
were active duty military at the time of surgery. The average age was 38.2 years.
There were 7 total complications (4.8%), including one failure (0.7%) requiring
revision. CONCLUSION: Failure and complication rates in the early postoperative
period using a unicortical suture button for biceps tenodesis fixation are
consistent with other reported techniques. This study adds clinical data to the
existing biomechanical reports that this technique is strong enough to provide
stable fixation of the biceps tendon to allow healing of the tendon to the
humerus.
PMID- 28701854
TI - Is linguistic injustice a myth? A response to Hyland (2016).
PMID- 28701855
TI - Honest Importance Sampling with Multiple Markov Chains.
AB - Importance sampling is a classical Monte Carlo technique in which a random sample
from one probability density, pi1, is used to estimate an expectation with
respect to another, pi. The importance sampling estimator is strongly consistent
and, as long as two simple moment conditions are satisfied, it obeys a central
limit theorem (CLT). Moreover, there is a simple consistent estimator for the
asymptotic variance in the CLT, which makes for routine computation of standard
errors. Importance sampling can also be used in the Markov chain Monte Carlo
(MCMC) context. Indeed, if the random sample from pi1 is replaced by a Harris
ergodic Markov chain with invariant density pi1, then the resulting estimator
remains strongly consistent. There is a price to be paid however, as the
computation of standard errors becomes more complicated. First, the two simple
moment conditions that guarantee a CLT in the iid case are not enough in the MCMC
context. Second, even when a CLT does hold, the asymptotic variance has a complex
form and is difficult to estimate consistently. In this paper, we explain how to
use regenerative simulation to overcome these problems. Actually, we consider a
more general set up, where we assume that Markov chain samples from several
probability densities, pi1, ..., pik , are available. We construct multiple-chain
importance sampling estimators for which we obtain a CLT based on regeneration.
We show that if the Markov chains converge to their respective target
distributions at a geometric rate, then under moment conditions similar to those
required in the iid case, the MCMC-based importance sampling estimator obeys a
CLT. Furthermore, because the CLT is based on a regenerative process, there is a
simple consistent estimator of the asymptotic variance. We illustrate the method
with two applications in Bayesian sensitivity analysis. The first concerns one
way random effects models under different priors. The second involves Bayesian
variable selection in linear regression, and for this application, importance
sampling based on multiple chains enables an empirical Bayes approach to variable
selection.
PMID- 28701856
TI - Psychotropic Medications and Their Effect on Brain Volumes in Childhood
Psychopathology.
PMID- 28701857
TI - Laparoscopic Single-Site Inguinal Hernia Repair Using a Self-Fixating Mesh.
AB - BACKGROUND AND OBJECTIVES: Every year ~20 million inguinal hernia repairs are
completed worldwide. Increased patient access to medical information and
education has elicited interest in minimally invasive surgical techniques that
obtain improved surgical outcomes and cosmesis. Because of these factors, there
is a growing interest in single-incision surgery. Laparoscopic totally
extraperitoneal (TEP) single-incision hernia repair technique has been reported
with different meshes used in a tack fixation system. Recently, self-fixating
mesh technology has offered the possibility of avoiding tack fixation and
potentially avoiding chronic postoperative pain. Self-fixating mesh technology
employs monofilament polylactic acid (PLA) creating a microgrip system that
provides self-adherence of the mesh to adjacent tissue. This tack-free fixation
system provides coverage over the entire myopectineal orifice and surrounding
areas where traditional tacks cannot be placed. Self-fixating mesh has also been
safely applied in laparoscopic TEP procedures, but this mesh has not been
described in single site TEP surgery; possibly because of the potential
difficulty with mesh deployment. We sought to determine the technical feasibility
of a single-site laparoscopic TEP repair of inguinal hernias and to discuss our
techniques and patient short-term outcomes. METHODS: Review of a prospectively
maintained database of patients who received single-site laparoscopic TEP
herniorrhaphy from August 2012 through August 2015. Patient characteristics and
demographics and perioperative and postoperative data were analyzed. RESULTS:
Thirty-four patients (aged 55.2 +/-14.2; 17.6% women) with a mean body mass index
of 26.2 +/- 3.9 were analyzed. Mean operative time was 99.5 +/- 30.5 minutes,
41.2% were left-side repairs, and 50% were bilateral. Estimated blood loss was
18.4 +/- 14.1 mL. Recurrent hernias accounted for 14.7% of cases; 32.4% of cases
were combination surgeries, most commonly a concurrent umbilical hernia repair.
The most common short-term postoperative complication was urinary retention (4
patients). The median length of follow-up was 25 days (IQR 18.75-61.75).
Complications occurring at >30 days included hydrocele (2 patients) and stitch
abscess (1 patient). Eight (23.5%) patients had complications (surgical or during
follow-up). No recurrences or deaths were reported. CONCLUSIONS: With comparable
operative times, perioperative outcomes, and safety profile, SS-TEP appears to be
a safe and effective surgical approach for the management of inguinal hernias in
the short term. Furthermore, SS-TEP with a self-fixating mesh is a feasible
approach.
PMID- 28701858
TI - Early Experience in Starting a Laparoscopic Liver Resection Program in Greece.
AB - BACKGROUND AND OBJECTIVES: Laparoscopic liver resections (LLRs) have gained wider
acceptance during the decade as safe and efficient procedures in the management
of several benign and malignant diseases when performed by experienced surgeons.
We report our initial institutional experience with LLRs performed by 1 certified
hepatobiliary surgeon. METHODS: Patients undergoing LLRs by 1 senior
hepatobiliary surgeon in our Institution during the period from January 2012
through January 2017 were prospectively sampled and retrospectively analyzed for
the purposes of this study. RESULTS: Forty-two of 175 patients (24%) who had
surgery for liver tumors underwent LLR. Median age was 64 years; median body mass
index and Charlson comorbidity index were 27.3 kg/m2 and 6.5, respectively.
Patients underwent resections for benign (n = 22) or malignant (n = 20) lesions.
Median total operating time was 115 minutes and liver resections included: 1 left
hepatectomy, 11 bisegmentectomies, 7 segmentectomies, 5 wide wedge resections, 1
left lateral sectionectomy combined with segmentectomy and radiofrequency
ablation, 15 liver cyst unroofing, 1 laparoscopic drainage of a pyogenic liver
abscess, and 1 laparoscopic drainage of a hepatic hydatid cyst. Blood transfusion
was needed in 10 patients. Six patients (14%) had postoperative complications,
none of which necessitated reoperation. None of the patients was admitted to the
intensive care unit after surgery, and the median hospital stay was 4 days. The
tumor-free resection margin was documented in all primary or secondary oncologic
cases. CONCLUSIONS: Careful patient selection and compliance with the
international recommendations are the keys for the successful introduction and
evolution of an LLR program with a certified hepatobiliary surgeon with
laparoscopic experience.
PMID- 28701860
TI - Noradrenaline, Serotonin, GABA, and Glycine in Cerebrospinal Fluid during Labor
Pain: A Cross-Sectional Prospective Study.
AB - BACKGROUND AND AIMS: The inhibitory pathways that play a role in spinal
modulation include local interneurons and descending control. Clinical data
regarding the role of these pathways in acute pain is lacking. Accordingly, the
aim of this study was to evaluate cerebrospinal fluid (CSF) levels of
noradrenaline, serotonin, gamma-aminobutyric acid (GABA), and glycine in
parturients with labor pain compared to those without labor pain. METHODS: One
hundred term uncomplicated pregnant women receiving spinal anesthesia for
cesarean section were enrolled in this prospective cross-sectional study. CSF
noradrenaline, serotonin, GABA, and glycine levels were analyzed by enzyme-linked
immunosorbent assay. Labor pain score was assessed by numerical rating scale.
RESULTS: Median CSF serotonin concentration in parturients with labor pain was
significantly lower than in those without pain (p < 0.001). Median CSF glycine
level in the labor pain group was significantly higher than in the control group
(p < 0.001). There were no significant differences in median CSF level of
noradrenaline or GABA between parturients with and without labor pain. Subsequent
analysis showed labor pain scores to be negatively correlated with CSF serotonin
(r = -0.217, p = 0.04) but positively correlated with CSF glycine (r = 0.415, p <
0.001). CONCLUSION: CSF serotonin and glycine were significantly correlated with
labor pain scores. These findings suggest that the serotonergic and glycinergic
systems may play a role in spinal modulation of visceral pain.
PMID- 28701859
TI - Advances in the pathophysiology and treatment of relapsed/refractory Hodgkin's
lymphoma with an emphasis on targeted therapies and transplantation strategies.
AB - Hodgkin's lymphoma (HL) is highly curable with first-line therapy. However, a
minority of patients present with refractory disease or experience relapse after
completion of frontline treatment. These patients are treated with salvage
chemotherapy followed by autologous stem cell transplantation (ASCT), which
remains the standard of care with curative potential for refractory or relapsed
HL. Nevertheless, a significant percentage of such patients will progress after
ASCT, and allogeneic hematopoietic stem cell transplantation remains the only
curative approach in that setting. Recent advances in the pathophysiology of
refractory or relapsed HL have provided the rationale for the development of
novel targeted therapies with potent anti-HL activity and favorable toxicity
profile, in contrast to cytotoxic chemotherapy. Brentuximab vedotin and
programmed cell death-1-based immunotherapy have proven efficacy in the
management of refractory or relapsed HL, whereas several other agents have shown
promise in early clinical trials. Several of these agents are being incorporated
with transplantation strategies in order to improve the outcomes of refractory or
relapsed HL. In this review we summarize the current knowledge regarding the
mechanisms responsible for the development of refractory/relapsed HL and the
outcomes with current treatment strategies, with an emphasis on targeted
therapies and hematopoietic stem cell transplantation.
PMID- 28701862
TI - Protective effect of ginsenosides Rk3 and Rh4 on cisplatin-induced acute kidney
injury in vitro and in vivo.
AB - BACKGROUND: Nephrotoxicity is the major side effect in cisplatin chemotherapy.
Previously, we reported that the ginsenosides Rk3 and Rh4 reduced cisplatin
toxicity on porcine renal proximal epithelial tubular cells (LLC-PK1). Here, we
aimed to evaluate the protective effect of ginsenosides Rk3 and Rh4 on kidney
function and elucidate their antioxidant effect using in vitro and in vivo models
of cisplatin-induced acute renal failure. METHODS: An enriched mixture of
ginsenosides Rk3 and Rh4 (KG-KH; 49.3% and 43.1%, respectively) was purified from
sun ginseng (heat processed Panax ginseng). Cytotoxicity was induced by treatment
of 20MUM cisplatin to LLC-PK1 cells and rat model of acute renal failure was
generated by single intraperitoneal injection of 5 mg/kg cisplatin. Protective
effects were assessed by determining cell viability, reactive oxygen species
generation, blood urea nitrogen, serum creatinine, antioxidant enzyme activity,
and histopathological examination. RESULTS: The in vitro assay demonstrated that
KG-KH (50 MUg/mL) significantly increased cell viability (4.6-fold), superoxide
dismutase activity (2.8-fold), and glutathione reductase activity (1.5-fold), but
reduced reactive oxygen species generation (56%) compared to cisplatin control
cells. KG-KH (6 mg/kg, per os) also significantly inhibited renal edema (87%
kidney index) and dysfunction (71.4% blood urea nitrogen, 67.4% creatinine)
compared to cisplatin control rats. Of note, KG-KH significantly recovered the
kidney levels of catalase (1.2-fold) and superoxide dismutase (1.5-fold).
CONCLUSION: Considering the oxidative injury as an early trigger of cisplatin
nephrotoxicity, our findings suggest that ginsenosides Rk3 and Rh4 protect the
kidney from cisplatin-induced oxidative injury and help to recover renal function
by restoring intrinsic antioxidant defenses.
PMID- 28701861
TI - A Preliminary Genome-Wide Association Study of Pain-Related Fear: Implications
for Orofacial Pain.
AB - BACKGROUND: Acute and chronic orofacial pain can significantly impact overall
health and functioning. Associations between fear of pain and the experience of
orofacial pain are well-documented, and environmental, behavioral, and cognitive
components of fear of pain have been elucidated. Little is known, however,
regarding the specific genes contributing to fear of pain. METHODS: A genome-wide
association study (GWAS; N = 990) was performed to identify plausible genes that
may predispose individuals to various levels of fear of pain. The total score and
three subscales (fear of minor, severe, and medical/dental pain) of the Fear of
Pain Questionnaire-9 (FPQ-9) were modeled in a variance components modeling
framework to test for genetic association with 8.5 M genetic variants across the
genome, while adjusting for sex, age, education, and income. RESULTS: Three
genetic loci were significantly associated with fear of minor pain (8q24.13,
8p21.2, and 6q26; p < 5 * 10-8 for all) near the genes TMEM65, NEFM, NEFL,
AGPAT4, and PARK2. Other suggestive loci were found for the fear of pain total
score and each of the FPQ-9 subscales. CONCLUSIONS: Multiple genes were
identified as possible candidates contributing to fear of pain. The findings may
have implications for understanding and treating chronic orofacial pain.
PMID- 28701863
TI - Inhibition of hypoxia-induced cyclooxygenase-2 by Korean Red Ginseng is dependent
on peroxisome proliferator-activated receptor gamma.
AB - BACKGROUND: Korean Red Ginseng (KRG) is a traditional herbal medicine made by
steaming and drying fresh ginseng. It strengthens the endocrine and immune
systems to ameliorate various inflammatory responses. The cyclooxygenase-2 (COX
2)/prostaglandin E2 pathway has important implications for inflammation responses
and tumorigenesis. Peroxisome proliferator-activated receptor gamma (PPARgamma)
is a transcription factor that regulates not only adipogenesis and lipid
homeostasis, but also angiogenesis and inflammatory responses. METHODS: The
effects of the KRG on inhibition of hypoxia-induced COX-2 via PPARgamma in A549
cells were determined by luciferase assay, Western blot, and/or quantitative
reverse transcription-polymerase chain reaction (qRT-PCR). The antimigration and
invasive effects of KRG were evaluated on A549 cells using migration and matrigel
invasion assays. RESULTS AND CONCLUSION: We previously reported that hypoxia
induced COX-2 protein and mRNA levels were suppressed by KRG. This study examines
the possibility of PPARgamma as a cellular target of KRG for the suppression of
hypoxia-induced COX-2. PPARgamma protein levels and PPARgamma-responsive element
(PPRE)-driven reporter activities were increased by KRG. Reduction of hypoxia
induced COX-2 by KRG was abolished by the PPARgamma inhibitor GW9662. In
addition, the inhibition of PPARgamma abolished the effect of KRG on hypoxia
induced cell migration and invasion. DISCUSSION: Our results show that KRG
inhibition of hypoxia-induced COX-2 expression and cell invasion is dependent on
PPARgamma activation, supporting the therapeutic potential for suppression of
inflammation under hypoxia. Further studies are required to demonstrate whether
KRG activates directly PPARgamma and to identify the constituents responsible for
this activity.
PMID- 28701864
TI - Induction of Forkhead Class box O3a and apoptosis by a standardized ginsenoside
formulation, KG-135, is potentiated by autophagy blockade in A549 human lung
cancer cells.
AB - BACKGROUND: KG-135, a standardized formulation enriched with Rk1, Rg3, and Rg5
ginsenosides, has been shown to inhibit various types of cancer cells; however,
the underlying mechanisms are not fully understood. In this study, we explored
its effects in A549 human lung cancer cells to investigate the induction of
Forkhead Class box O3a (FOXO3a) and autophagy. METHODS: Cell viability was
determined by sulforhodamine B staining. Apoptosis and cell cycle distribution
were analyzed using flow cytometry. The changes of protein levels were determined
using Western blot analysis. Autophagy induction was monitored by the formation
of acidic vesicular organelles stained with acridine orange. RESULTS: KG-135
effectively arrested the cells in G1 phase with limited apoptosis. Accordingly, a
decrease of cyclin-dependent kinase-4, cyclin-dependent kinase-6, cyclin D1, and
phospho-retinoblastoma protein, and an increase of p27 and p18 proteins were
observed. Intriguingly, KG-135 increased the tumor suppressor FOXO3a and induced
the accumulation of autophagy hallmark LC3-II and acidic vesicular organelles
without an increase of the upstream marker Beclin-1. Unconventionally, the
autophagy adaptor protein p62 (sequestosome 1) was increased rather than
decreased. Blockade of autophagy by hydroxychloroquine dramatically potentiated
KG-135-induced FOXO3a and its downstream (FasL) ligand accompanied by the
cleavage of caspase-8. Meanwhile, the decrease of Bcl-2 and survivin, as well as
the cleavage of caspase-9, were also drastically enhanced, resulting in massive
apoptosis. CONCLUSION: Besides arresting the cells in G1 phase, KG-135 increased
FOXO3a and induced an unconventional autophagy in A549 cells. Both the KG-135
activated extrinsic FOXO3a/FasL/caspase-8 and intrinsic caspase-9 apoptotic
pathways were potentiated by blockade of autophagy. Combination of KG-135 and
autophagy inhibitor may be a novel strategy as an integrative treatment for
cancers.
PMID- 28701865
TI - Processed Panax ginseng, sun ginseng, inhibits the differentiation and
proliferation of 3T3-L1 preadipocytes and fat accumulation in Caenorhabditis
elegans.
AB - BACKGROUND: Heat-processed ginseng, sun ginseng (SG), has been reported to have
improved therapeutic properties compared with raw forms, such as increased
antidiabetic, anti-inflammatory, and antihyperglycemic effects. The aim of this
study was to investigate the antiobesity effects of SG through the suppression of
cell differentiation and proliferation of mouse 3T3-L1 preadipocyte cells and the
lipid accumulation in Caenorhabditis elegans. METHODS: To investigate the effect
of SG on adipocyte differentiation, levels of stained intracellular lipid
droplets were quantified by measuring the oil red O signal in the lipid extracts
of cells on differentiation Day 7. To study the effect of SG on fat accumulation
in C. elegans, L4 stage worms were cultured on an Escherichia coli OP50 diet
supplemented with 10 MUg/mL of SG, followed by Nile red staining. To determine
the effect of SG on gene expression of lipid and glucose metabolism-regulation
molecules, messenger RNA (mRNA) levels of genes were analyzed by real-time
reverse transcription-polymerase chain reaction analysis. In addition, the
phosphorylation of Akt was examined by Western blotting. RESULTS: SG suppressed
the differentiation of 3T3-L1 cells stimulated by a mixture of 3-isobutyl-1
methylxanthine, dexamethasone, and insulin (MDI), and inhibited the proliferation
of adipocytes during differentiation. Treatment of C. elegans with SG showed
reductions in lipid accumulation by Nile red staining, thus directly
demonstrating an antiobesity effect for SG. Furthermore, SG treatment
downregulated mRNA and protein expression levels of peroxisome proliferator
activated receptor subtype gamma (PPARgamma) and CCAAT/enhancer-binding protein
alpha (C/EBPalpha) and decreased the mRNA level of sterol regulatory element
binding protein 1c in MDI-treated adipocytes in a dose-dependent manner. In
differentiated 3T3-L1 cells, mRNA expression levels of lipid metabolism
regulating factors, such as amplifying mouse fatty acid-binding protein 2,
leptin, lipoprotein lipase, fatty acid transporter protein 1, fatty acid
synthase, and 3-hydroxy-3-methylglutaryl coenzyme A reductase, were increased,
whereas that of the lipolytic enzyme carnitine palmitoyltransferase-1 was
decreased. Our data demonstrate that SG inversely regulated the expression of
these genes in differentiated adipocytes. SG induced increases in the mRNA
expression of glycolytic enzymes such as glucokinase and pyruvate kinase, and a
decrease in the mRNA level of the glycogenic enzyme phosphoenol pyruvate
carboxylase. In addition, mRNA levels of the glucose transporters GLUT1, GLUT4,
and insulin receptor substrate-1 were elevated by MDI stimulation, whereas SG
dose-dependently inhibited the expression of these genes in differentiated
adipocytes. SG also inhibited the phosphorylation of Akt (Ser473) at an early
phase of MDI stimulation. Intracellular nitric oxide (NO) production and
endothelial nitric oxide synthase mRNA levels were markedly decreased by MDI
stimulation and recovered by SG treatment of adipocytes. CONCLUSION: Our results
suggest that SG effectively inhibits adipocyte proliferation and differentiation
through the downregulation of PPARgamma and C/EBPalpha, by suppressing Akt
(Ser473) phosphorylation and enhancing NO production. These results provide
strong evidence to support the development of SG for antiobesity treatment.
PMID- 28701866
TI - Inhibitory effects of ginsenosides on basic fibroblast growth factor-induced
melanocyte proliferation.
AB - BACKGROUND: UV-B-exposed keratinocytes secrete various paracrine factors. Among
these factors, basic fibroblast growth factor (bFGF) stimulates the proliferation
of melanocytes. Ginsenosides, the major active compounds of ginseng, are known to
have broad pharmacological effects. In this study, we examined the
antiproliferative effects of ginsenosides on bFGF-induced melanocyte
proliferation. METHODS: We investigated the inhibitory effects of Korean Red
Ginseng and ginsenosides from Panax ginseng on bFGF-induced proliferation of
melan-a melanocytes. RESULTS: When melan-a melanocytes were treated with UV-B
irradiated SP-1 keratinocytes media, cell proliferation increased. This increased
proliferation of melanocytes decreased with a neutralizing anti-bFGF antibody. To
elucidate the effects of ginsenosides on melanocyte proliferation induced by
bFGF, we tested 15 types of ginsenoside compounds. Among them, Rh3, Rh1, F1, and
CK demonstrated antiproliferative effects on bFGF-induced melanocyte
proliferation after 72 h of treatment. bFGF stimulated cell proliferation via
extracellular signal-regulated kinase (ERK) activation in various cell types.
Western blot analysis found bFGF-induced ERK phosphorylation in melan-a.
Treatment with Rh3 inhibited bFGF-induced maximum ERK phosphorylation and F1
delayed maximum ERK phosphorylation, whereas Rh1 and CK had no detectable
effects. In addition, cotreatment with Rh3 and F1 significantly suppressed bFGF
induced ERK phosphorylation. Western blot analysis found that bFGF increased
microphthalmia-associated transcription factor (MITF) protein levels in melan-a.
Treatment with Rh3 or F1 had no detectable effects, whereas cotreatment with Rh3
and F1 inhibited bFGF-induced MITF expression levels more strongly than a single
treatment. CONCLUSION: In summary, we found that ginsenosides Rh3 and F1 have a
synergistic antiproliferative effect on bFGF-induced melan-a melanocyte
proliferation via the inhibition of ERK-mediated upregulation of MITF.
PMID- 28701867
TI - Effects of Korean ginseng berry on skin antipigmentation and antiaging via FoxO3a
activation.
AB - BACKGROUND: The ginseng berry has various bioactivities, including antidiabetic,
anticancer, antiinflammatory, and antioxidative properties. Moreover, we have
revealed that the active antiaging component of the ginseng berry,
syringaresinol, has the ability to stimulate longevity via gene activation.
Despite the many known beneficial effects of ginseng, its effects on skin aging
are poorly understood. In this study, we investigated the effects of ginseng and
the ginseng berry on one of the skin aging processes, melanogenesis, and age
related pigment lipofuscin accumulation, to elucidate the mechanism of action
with respect to antiaging. METHODS: The human melanoma MNT1 cell line was treated
with ginseng root extract, ginseng berry extract, or syringaresinol. Then, the
cells were analyzed using a melanin assay, and the tyrosinase activity was
estimated. The Caenorhabditis elegans wild type N2 strain was used for the life
span assay to analyze the antiaging effects of the samples. A lipofuscin
fluorescence assay was performed during 10 passages with the syringaresinol
treatment. RESULTS: A 7-d treatment with ginseng berry extract reduced melanin
accumulation and tyrosinase activity more than ginseng root extract. These
results may be due to the active compound of the ginseng berry, syringaresinol.
The antimelanogenic activity was strongly coordinated with the activation of the
longevity gene foxo3a. Moreover, the ginseng berry extract had more potent
antiaging effects, caused a life span extension, and reduced lipofuscin
accumulation. CONCLUSION: Taken together, our results suggest that these
antimelanogenic effects and antiaging effects of ginseng berry mediate the
activation of antioxidation-FoxO3a signaling.
PMID- 28701868
TI - Protective effect of Korean Red Ginseng against FK506-induced damage in LLC-PK1
cells.
AB - BACKGROUND: Compound FK506 is an immunosuppressant agent that is frequently used
to prevent rejection of solid organs upon transplant. However, nephrotoxicity due
to apoptosis and inflammatory response mediated by FK506 limit its usefulness. In
this study, the protective effect of Korean Red Ginseng (KRG) against FK506
induced damage in LLC-PK1 pig kidney epithelial cells was investigated. METHODS:
LLC-PK1 cells were exposed to FK506 with KRG and cell viability was measured.
Western blotting and RT-PCR analyses evaluated protein expression of MAPKs,
caspase-3, and KIM-1. TLR-4 gene expression was assessed. Caspase-3 activities
were also determined. The number of apoptotic cells was measured using an image
based cytometric assay. RESULTS: The reduction in LLC-PK1 cell viability by 60MUM
FK506 was recovered by KRG cotreatment in a dose-dependent manner. The
phosphorylation of p38, p44/42 MAPKs (ERK), KIM-1, cleaved caspase-3, and TLR-4
mRNA expression was increased markedly in LLC-PK1 cells treated with 60MUM FK506.
However, with the exception of p-ERK, elevated levels of p-p38, KIM-1, cleaved
caspase-3, and TLR-4 mRNA expression were significantly decreased after
cotreatment with KRG. Activity level of caspase-3 was also attenuated by KRG
cotreatment. Moreover, image-based cytometric assay showed that apoptotic cell
death was increased by 60MUM FK506 treatment, whereas it was decreased after
cotreatment with KRG. CONCLUSION: Taken together, these results suggest that the
molecular mechanism of KRG in the FK506-induced nephrotoxicity may lead to the
development of an adjuvant for the inhibition of adverse effect FK506 in the
kidney.
PMID- 28701869
TI - Identification of ginseng root using quantitative X-ray microtomography.
AB - BACKGROUND: The use of X-ray phase-contrast microtomography for the investigation
of Chinese medicinal materials is advantageous for its nondestructive, in situ,
and three-dimensional quantitative imaging properties. METHODS: The X-ray phase
contrast microtomography quantitative imaging method was used to investigate the
microstructure of ginseng, and the phase-retrieval method is also employed to
process the experimental data. Four different ginseng samples were collected and
investigated; these were classified according to their species, production area,
and sample growth pattern. RESULTS: The quantitative internal characteristic
microstructures of ginseng were extracted successfully. The size and position
distributions of the calcium oxalate cluster crystals (COCCs), important
secondary metabolites that accumulate in ginseng, are revealed by the three
dimensional quantitative imaging method. The volume and amount of the COCCs in
different species of the ginseng are obtained by a quantitative analysis of the
three-dimensional microstructures, which shows obvious difference among the four
species of ginseng. CONCLUSION: This study is the first to provide evidence of
the distribution characteristics of COCCs to identify four types of ginseng, with
regard to species authentication and age identification, by X-ray phase-contrast
microtomography quantitative imaging. This method is also expected to reveal
important relationships between COCCs and the occurrence of the effective
medicinal components of ginseng.
PMID- 28701870
TI - Nuclear factor kappa-B- and activator protein-1-mediated immunostimulatory
activity of compound K in monocytes and macrophages.
AB - BACKGROUND: Compound K (CK) is a bioactive derivative of ginsenoside Rb1 in Panax
ginseng (Korean ginseng). Its biological and pharmacological activities have been
studied in various disease conditions, although its immunomodulatory role in
innate immunity mediated by monocytes/macrophages has been poorly understood. In
this study, we aimed to elucidate the regulatory role of CK on cellular events
mediated by monocytes and macrophages in innate immune responses. METHODS: The
immunomodulatory role of CK was explored by various immunoassays including cell
cell adhesion, fibronectin adhesion, cell migration, phagocytic uptake,
costimulatory molecules, reactive oxygen species production, luciferase activity,
and by the measurement of mRNA levels of proinflammatory genes. RESULTS: Compound
K induced cell cluster formation through cell-cell adhesion, cell migration, and
phagocytic activity, but it suppressed cell-tissue interactions in U937 and
RAW264.7 cells. Compound K also upregulated the surface expression of the cell
adhesion molecule cluster of differentiation (CD) 43 (CD43) and costimulatory
molecules CD69, CD80, and CD86, but it downregulated the expression of monocyte
differentiation marker CD82 in RAW264.7 cells. Moreover, CK induced the release
of reactive oxygen species and induced messenger RNA expression of
proinflammatory genes, inducible nitric oxide synthase, and tumor necrosis factor
alpha by enhancing the nuclear translocation and transcriptional activities of
nuclear factor kappa-B and activator protein-1. CONCLUSION: Our results suggest
that CK has an immunomodulatory role in innate immune responses through
regulating various cellular events mediated by monocytes and macrophages.
PMID- 28701871
TI - Changes in element accumulation, phenolic metabolism, and antioxidative enzyme
activities in the red-skin roots of Panax ginseng.
AB - BACKGROUND: Red-skin root disease has seriously decreased the quality and
production of Panax ginseng (ginseng). METHODS: To explore the disease's origin,
comparative analysis was performed in different parts of the plant, particularly
the epidermis, cortex, and/or fibrous roots of 5-yr-old healthy and diseased red
skin ginseng. The inorganic element composition, phenolic compound concentration,
reactive oxidation system, antioxidant concentrations such as ascorbate and
glutathione, activities of enzymes related to phenolic metabolism and oxidation,
and antioxidative system particularly the ascorbate-glutathione cycle were
examined using conventional methods. RESULTS: Aluminum (Al), iron (Fe),
magnesium, and phosphorus were increased, whereas manganese was unchanged and
calcium was decreased in the epidermis and fibrous root of red-skin ginseng,
which also contained higher levels of phenolic compounds, higher activities of
the phenolic compound-synthesizing enzyme phenylalanine ammonia-lyase and the
phenolic compound oxidation-related enzymes guaiacol peroxidase and
polyphenoloxidase. As the substrate of guaiacol peroxidase, higher levels of H2O2
and correspondingly higher activities of superoxide dismutase and catalase were
found in red-skin ginseng. Increased levels of ascorbate and glutathione;
increased activities of l-galactose 1-dehydrogenase, ascorbate peroxidase,
ascorbic acid oxidase, and glutathione reductase; and lower activities of
dehydroascorbate reductase, monodehydroascorbate reductase, and glutathione
peroxidase were found in red-skin ginseng. Glutathione-S-transferase activity
remained constant. CONCLUSION: Hence, higher element accumulation, particularly
Al and Fe, activated multiple enzymes related to accumulation of phenolic
compounds and their oxidation. This might contribute to red-skin symptoms in
ginseng. It is proposed that antioxidant and antioxidative enzymes, especially
those involved in ascorbate-glutathione cycles, are activated to protect against
phenolic compound oxidation.
PMID- 28701872
TI - Ginseng essence, a medicinal and edible herbal formulation, ameliorates carbon
tetrachloride-induced oxidative stress and liver injury in rats.
AB - BACKGROUND: Ginseng essence (GE) is a formulation comprising four medicinal and
edible herbs including ginseng (Panax ginseng), American ginseng (Panax
quinquefolius), lotus seed (Nelumbo nucifera), and lily bulb (Lilium
longiflorum). This study was aimed at investigating the hepatoprotective effect
of GE against carbon tetrachloride (CCl4)-induced liver injury in rats. METHODS:
We treated Wistar rats daily with low, medium, and high [0.625 g/kg body weight
(bw), 1.25 g/kg bw, and 3.125 g/kg bw, respectively] doses of GE for 9 wk. After
the 1st wk of treatment, rats were administered 20% CCl4 (1.5 mL/kg bw) two times
a week to induce liver damage until the treatment ended. RESULTS: Serum
biochemical analysis indicated that GE ameliorated the elevation of aspartate
aminotransferase and alanine aminotransferase and albumin decline in CCl4-treated
rats. Moreover, CCl4-induced accumulation of hepatic total cholesterol and
triglyceride was inhibited. The hepatoprotective effects of GE involved enhancing
the hepatic antioxidant defense system including glutathione, glutathione
peroxidase, glutathione reductase, glutathione S-transferase, superoxide
dismutase, and catalase. In addition, histological analysis using hematoxylin and
eosin and Masson's trichrome staining showed that GE inhibited CCl4-induced
hepatic inflammation and fibrosis. Furthermore, immunohistochemical staining of
alpha-smooth muscle actin indicated that CCl4-triggered activation of hepatic
stellate cells was reduced. CONCLUSION: These findings demonstrate that GE
improves CCl4-induced liver inflammation and fibrosis by attenuating oxidative
stress. Therefore, GE could be a promising hepatoprotective herbal formulation
for future development of phytotherapy.
PMID- 28701873
TI - Molecular differentiation of Russian wild ginseng using mitochondrial nad7 intron
3 region.
AB - BACKGROUND: Cultivated ginseng is often introduced as a substitute and adulterant
of Russian wild ginseng due to its lower cost or misidentification caused by
similarity in appearance with wild ginseng. The aim of this study is to develop a
simple and reliable method to differentiate Russian wild ginseng from cultivated
ginseng. METHODS: The mitochondrial NADH dehydrogenase subunit 7 (nad7) intron 3
regions of Russian wild ginseng and Chinese cultivated ginseng were analyzed.
Based on the multiple sequence alignment result, a specific primer for Russian
wild ginseng was designed by introducing additional mismatch and allele-specific
polymerase chain reaction (PCR) was performed for identification of wild ginseng.
Real-time allele-specific PCR with endpoint analysis was used for validation of
the developed Russian wild ginseng single nucleotide polymorphism (SNP) marker.
RESULTS: An SNP site specific to Russian wild ginseng was exploited by multiple
alignments of mitochondrial nad7 intron 3 regions of different ginseng samples.
With the SNP-based specific primer, Russian wild ginseng was successfully
discriminated from Chinese and Korean cultivated ginseng samples by allele
specific PCR. The reliability and specificity of the SNP marker was validated by
checking 20 individuals of Russian wild ginseng samples with real-time allele
specific PCR assay. CONCLUSION: An effective DNA method for molecular
discrimination of Russian wild ginseng from Chinese and Korean cultivated ginseng
was developed. The established real-time allele-specific PCR was simple and
reliable, and the present method should be a crucial complement of chemical
analysis for authentication of Russian wild ginseng.
PMID- 28701874
TI - The interaction of serum albumin with ginsenoside Rh2 resulted in the
downregulation of ginsenoside Rh2 cytotoxicity.
AB - BACKGROUND: Ginsenoside Rh2 (G-Rh2) is a ginseng saponin that is widely
investigated because of its remarkable antitumor activity. However, the molecular
mechanism by which (20S) G-Rh2 triggers its functions and how target animals
avoid its cytotoxic action remains largely unknown. METHODS: Phage display was
used to screen the human targets of (20S) G-Rh2. Fluorescence spectroscopy and UV
visible absorption spectroscopy were used to confirm the interaction of candidate
target proteins and (20S) G-Rh2. Molecular docking was utilized to calculate the
estimated free energy of binding and to structurally visualize their
interactions. MTT assay and immunoblotting were used to assess whether human
serum albumin (HSA), bovine serum albumin (BSA), and bovine serum can reduce the
cytotoxic activity of (20S) G-Rh2 in HepG2 cells. RESULTS: In phage display,
(20S) G-Rh2-beads and (20R) G-Rh2-beads were combined with numerous kinds of
phages, and a total of 111 different human complementary DNAs (cDNA) were
identified, including HSA which had the highest rate. The binding constant and
number of binding site in the interaction between (20S)-Rh2 and HSA were 3.5 *
105 M-1 and 1, and those in the interaction between (20S) G-Rh2 and BSA were 1.4
* 105 M-1 and 1. The quenching mechanism is static quenching. HSA, BSA and bovine
serum significantly reduced the proapoptotic effect of (20S) G-Rh2. CONCLUSION:
HSA and BSA interact with (20S) G-Rh2. Serum inhibited the activity of (20S) G
Rh2 mainly due to the interaction between (20S) G-Rh2 and serum albumin (SA).
This study proposes that HSA may enhance (20S) G-Rh2 water solubility, and thus
might be used as nanoparticles in the (20S) G-Rh2 delivery process.
PMID- 28701875
TI - Converting Panax ginseng DNA and chemical fingerprints into two-dimensional
barcode.
AB - BACKGROUND: In this study, we investigated how to convert the Panax ginseng DNA
sequence code and chemical fingerprints into a two-dimensional code. In order to
improve the compression efficiency, GATC2Bytes and digital merger compression
algorithms are proposed. METHODS: HPLC chemical fingerprint data of 10 groups of
P. ginseng from Northeast China and the internal transcribed spacer 2 (ITS2)
sequence code as the DNA sequence code were ready for conversion. In order to
convert such data into a two-dimensional code, the following six steps were
performed: First, the chemical fingerprint characteristic data sets were obtained
through the inflection filtering algorithm. Second, precompression processing of
such data sets is undertaken. Third, precompression processing was undertaken
with the P. ginseng DNA (ITS2) sequence codes. Fourth, the precompressed chemical
fingerprint data and the DNA (ITS2) sequence code were combined in accordance
with the set data format. Such combined data can be compressed by Zlib, an open
source data compression algorithm. Finally, the compressed data generated a two
dimensional code called a quick response code (QR code). RESULTS: Through the
abovementioned converting process, it can be found that the number of bytes
needed for storing P. ginseng chemical fingerprints and its DNA (ITS2) sequence
code can be greatly reduced. After GTCA2Bytes algorithm processing, the ITS2
compression rate reaches 75% and the chemical fingerprint compression rate
exceeds 99.65% via filtration and digital merger compression algorithm
processing. Therefore, the overall compression ratio even exceeds 99.36%. The
capacity of the formed QR code is around 0.5k, which can easily and successfully
be read and identified by any smartphone. CONCLUSION: P. ginseng chemical
fingerprints and its DNA (ITS2) sequence code can form a QR code after data
processing, and therefore the QR code can be a perfect carrier of the
authenticity and quality of P. ginseng information. This study provides a
theoretical basis for the development of a quality traceability system of
traditional Chinese medicine based on a two-dimensional code.
PMID- 28701876
TI - Effects of Panax ginseng extracts prepared at different steaming times on
thermogenesis in rats.
AB - BACKGROUND: Panax ginseng (PG) has a long history of use in Asian medicine
because of its multiple pharmacological activities. It has been considered that
PG in a type of white ginseng may induce undesirable thermogenic effects, but not
in a type of red ginseng. However, there is a lack of evidence about the
correlation between ginsenoside and thermogenesis. METHODS: We investigated the
effects of PG with different ginsenoside compositions on body temperature, blood
pressure, and thermogenesis-related factors in rats. RESULTS: With increasing
steaming time (0 h, 3 h, 6 h, and 9 h), the production of protopanaxadiol
ginsenosides increased, whereas protopanaxatriol ginsenosides decreased in white
ginseng. In both short- and long-term studies, administration of four ginseng
extracts prepared at different steaming times did not induce significant changes
in body temperature (skin, tail, and rectum) and blood pressure of rats compared
to saline control. In addition, there were no significant differences in the
molecular markers related to thermogenesis (p > 0.05), mRNA expressions of
peroxisome proliferator-activated receptor-gamma coactivator-1alpha and
uncoupling protein 1 in brown adipose tissue, as well as the serum levels of
interleukin-6, inducible nitric oxide synthase, and nitrite among the treatment
groups. CONCLUSION: These observations indicate that the potential undesirable
effects of PG on body temperature could not be explained by the difference in
ginsenoside composition.
PMID- 28701877
TI - Endophytic fungi harbored in Panax notoginseng: diversity and potential as
biological control agents against host plant pathogens of root-rot disease.
AB - BACKGROUND: Endophytic fungi play an important role in balancing the ecosystem
and boosting host growth. In the present study, we investigated the endophytic
fungal diversity of healthy Panax notoginseng and evaluated its potential
antimicrobial activity against five major phytopathogens causing root-rot of P.
notoginseng. METHODS: A culture-dependent technique, combining morphological and
molecular methods, was used to analyze endophytic fungal diversity. A double
layer agar technique was used to challenge the phytopathogens of P. notoginseng.
RESULTS: A total of 89 fungi were obtained from the roots, stems, leaves, and
seeds of P. notoginseng, and 41 isolates representing different morphotypes were
selected for taxonomic characterization. The fungal isolates belonged to
Ascomycota (96.6%) and Zygomycota (3.4%). All isolates were classified to 23
genera and an unknown taxon belonging to Sordariomycetes. The number of isolates
obtained from different tissues ranged from 12 to 42 for leaves and roots,
respectively. The selected endophytic fungal isolates were challenged by the root
rot pathogens Alternaria panax, Fusarium oxysporum, Fusarium solani, Phoma
herbarum, and Mycocentrospora acerina. Twenty-six of the 41 isolates (63.4%)
exhibited activity against at least one of the pathogens tested. CONCLUSION: Our
results suggested that P. notoginseng harbors diversified endophytic fungi that
would provide a basis for the identification of new bioactive compounds, and for
effective biocontrol of notoginseng root rot.
PMID- 28701878
TI - In situ analysis of chemical components induced by steaming between fresh
ginseng, steamed ginseng, and red ginseng.
AB - BACKGROUND: The chemical constituents of Panax ginseng are changed by processing
methods such as steaming or sun drying. In the present study, the chemical change
of Panax ginseng induced by steaming was monitored in situ. METHODS: Samples were
separated from the same ginseng root by incision during the steaming process, for
in situ monitoring. Sampling was sequentially performed in three stages; FG
(fresh ginseng) -> SG (steamed ginseng) -> RG (red ginseng) and 60 samples were
prepared and freeze dried. The samples were then analyzed to determine 43
constituents among three stages of P. ginseng. RESULTS: The results showed that
six malonyl-ginsenoside (Rg1, Rb1, Rb3, Rc, Rd, Rb2) and 15 amino acids were
decreased in concentration during the steaming process. In contrast, ginsenoside
Rh1, 20(S)-Rg2, 20(S, R)-Rg3 and Maillard reaction product such as AF (arginine
fructose), AFG (arginine-fructose-glucose), and maltol were newly generated or
their concentrations were increased. CONCLUSION: This study elucidates the
dynamic changes in the chemical components of P. ginseng when the steaming
process was induced. These results are thought to be helpful for quality control
and standardization of herbal drugs using P. ginseng and they also provide a
scientific basis for pharmacological research of processed ginseng (Red ginseng).
PMID- 28701879
TI - Optimal light for greenhouse culture of American ginseng seedlings.
AB - Three greenhouse experiments with American ginseng seedlings growing under light
levels from 4.8% to 68% showed a quadratic response for root dry weight, giving
an optimal root dry weight of 239 mg (range 160-415 mg) at an optimal light level
of 35.6% (range 30.6-43.2%).
PMID- 28701880
TI - Discovery, semisynthesis, biological activities, and metabolism of ocotillol-type
saponins.
AB - Ocotillol-type saponins are one kind of tetracyclic triterpenoids, sharing a
tetrahydrofuran ring. Natural ocotillol-type saponins have been discovered in
Panax quinquefolius L., Panax japonicus, Hana mina, and Vietnamese ginseng. In
recent years, the semisynthesis of 20(S/R)-ocotillol-type saponins has been
reported. The biological activities of ocotillol-type saponins include
neuroprotective effect, antimyocardial ischemia, antiinflammatory, antibacterial,
and antitumor activities. Owing to their chemical structure, pharmacological
actions, and the stereoselective activity on antimyocardial ischemia, ocotillol
type saponins are subjected to extensive consideration. In this review, we sum up
the discovery, semisynthesis, biological activities, and metabolism of ocotillol
type saponins.
PMID- 28701881
TI - A comparative study on chemical composition of total saponins extracted from
fermented and white ginseng under the effect of macrophage phagocytotic function.
AB - In this study, white ginseng was used as the raw material, which was fermented
with Paecilomyces hepiali through solid culture medium, to produce ginsenosides
with modified chemical composition. The characteristic chemical markers of the
products thus produced were investigated using rapid resolution liquid
chromatography coupled with quadrupole time-of-flight mass spectrometry (RRLC
QTOF-MS). Chemical profiling data were obtained, which were then subjected to
multivariate statistical analysis for the systematic comparison of active
ingredients in white ginseng and fermented ginseng to understand the beneficial
properties of ginsenoside metabolites. In addition, the effects of these
components on biological activity were investigated to understand the
improvements in the phagocytic function of macrophages in zebrafish. According to
the established RRLC-QTOF-MS chemical profiling, the contents in ginsenosides of
high molecular weight, especially malonylated protopanaxadiol ginsenosides, were
slightly reduced due to the fermentation, which were hydrolyzed into rare and
minor ginsenosides. Moreover, the facilitation of macrophage phagocytic function
in zebrafish following treatment with different ginseng extracts confirmed that
the fermented ginseng is superior to white ginseng. Our results prove that there
is a profound change in chemical constituents of ginsenosides during the
fermentation process, which has a significant effect on the biological activity
of these compounds.
PMID- 28701882
TI - Comparison of anticancer activities of Korean Red Ginseng-derived fractions.
AB - BACKGROUND: Korean Red Ginseng (KRG) is an ethnopharmacological plant that is
traditionally used to improve the body's immune functions and ameliorate the
symptoms of various diseases. However, the antitumorigenic effects of KRG and its
underlying molecular and cellular mechanisms are not fully understood in terms of
its individual components. In this study, in vitro and in vivo antitumorigenic
activities of KRG were explored in water extract (WE), saponin fraction (SF), and
nonsaponin fraction (NSF). METHODS: In vitro antitumorigenic activities of WE,
SF, and NSF of KRG were investigated in the C6 glioma cell line using
cytotoxicity, migration, and proliferation assays. The underlying molecular
mechanisms of KRG fractions were determined by examining the signaling cascades
of apoptotic cell death by semiquantitative reverse transcriptase polymerase
chain reaction and Western blot analysis. The in vivo antitumorigenic activities
of WE, SF, and NSF were investigated in a xenograft mouse model. RESULTS: SF
induced apoptotic death of C6 glioma cells and suppressed migration and
proliferation of C6 glioma cells, whereas WE and NSF neither induced apoptosis
nor suppressed migration of C6 glioma cells. SF downregulated the expression of
the anti-apoptotic gene B-cell lymphoma-2 (Bcl-2) and upregulated the expression
of the pro-apoptotic gene Bcl-2-associated X protein (BAX) in C6 glioma cells but
had no effect on the expression of the p53 tumor-suppressor gene. Moreover, SF
treatment resulted in activation of caspase-3 as evidenced by increased levels of
cleaved caspase-3. Finally, WE, SF, and NSF exhibited in vivo antitumorigenic
activities in the xenograft mouse model by suppressing the growth of grafted CT
26 carcinoma cells without decreasing the animal body weight. CONCLUSION: These
results suggest that WE, SF, and NSF of KRG are able to suppress tumor growth via
different molecular and cellular mechanisms, including induction of apoptosis and
activation of immune cells.
PMID- 28701883
TI - 20S-Protopanaxadiol, an aglycosylated ginsenoside metabolite, induces hepatic
stellate cell apoptosis through liver kinase B1-AMP-activated protein kinase
activation.
AB - BACKGROUND: Previously, we reported that Korean Red Ginseng inhibited liver
fibrosis in mice and reduced the expressions of fibrogenic genes in hepatic
stellate cells (HSCs). The present study was undertaken to identify the major
ginsenoside responsible for reducing the numbers of HSCs and the underlying
mechanism involved. METHODS: Using LX-2 cells (a human immortalized HSC line) and
primary activated HSCs, MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl
tetrazolium bromide) assays were conducted to examine the cytotoxic effects of
ginsenosides. H2O2 productions, glutathione contents, lactate dehydrogenase
activities, mitochondrial membrane permeabilities, apoptotic cell subpopulations,
caspase-3/-7 activities, transferase dUTP nick end labeling (TUNEL) staining, and
immunoblot analysis were performed to elucidate the molecular mechanism
responsible for ginsenoside-mediated cytotoxicity. Involvement of the AMP
activated protein kinase (AMPK)-related signaling pathway was examined using a
chemical inhibitor and small interfering RNA (siRNA) transfection. RESULTS AND
CONCLUSION: Of the 11 ginsenosides tested, 20S-protopanaxadiol (PPD) showed the
most potent cytotoxic activity in both LX-2 cells and primary activated HSCs.
Oxidative stress-mediated apoptosis induced by 20S-PPD was blocked by N-acetyl-l
cysteine pretreatment. In addition, 20S-PPD concentration-dependently increased
the phosphorylation of AMPK, and compound C prevented 20S-PPD-induced
cytotoxicity and mitochondrial dysfunction. Moreover, 20S-PPD increased the
phosphorylation of liver kinase B1 (LKB1), an upstream kinase of AMPK. Likewise,
transfection of LX-2 cells with LKB1 siRNA reduced the cytotoxic effect of 20S
PPD. Thus, 20S-PPD appears to induce HSC apoptosis by activating LKB1-AMPK and to
be a therapeutic candidate for the prevention or treatment of liver fibrosis.
PMID- 28701884
TI - cis-Prenyltransferase interacts with a Nogo-B receptor homolog for dolichol
biosynthesis in Panax ginseng Meyer.
AB - BACKGROUND: Prenyltransferases catalyze the sequential addition of isopentenyl
diphosphate units to allylic prenyl diphosphate acceptors and are classified as
either trans-prenyltransferases (TPTs) or cis-prenyltransferases (CPTs). The
functions of CPTs have been well characterized in bacteria, yeast, and mammals
compared to plants. The characterization of CPTs also has been less studied than
TPTs. In the present study, molecular cloning and functional characterization of
a CPT from a medicinal plant, Panax ginseng Mayer were addressed. METHODS: Gene
expression patterns of PgCPT1 were analyzed by quantitative reverse transcription
polymerase chain reaction. In planta transformation was generated by floral
dipping using Agrobacterium tumefaciens. Yeast transformation was performed by
lithium acetate and heat-shock for rer2Delta complementation and yeast-two-hybrid
assay. RESULTS: The ginseng genome contains at least one family of three putative
CPT genes. PgCPT1 is expressed in all organs, but more predominantly in the
leaves. Overexpression of PgCPT1 did not show any plant growth defect, and its
protein can complement yeast mutant rer2Delta via possible protein-protein
interaction with PgCPTL2. CONCLUSION: Partial complementation of the yeast
dolichol biosynthesis mutant rer2Delta suggested that PgCPT1 is involved in
dolichol biosynthesis. Direct protein interaction between PgCPT1 and a human Nogo
B receptor homolog suggests that PgCPT1 requires an accessory component for
proper function.
PMID- 28701885
TI - Panax ginseng total protein promotes proliferation and secretion of collagen in
NIH/3T3 cells by activating extracellular signal-related kinase pathway.
AB - BACKGROUND: Recently, protein from ginseng was studied and used for the treatment
of several kinds of diseases. However, the effect of ginseng total protein (GTP)
on proliferation and wound healing in fibroblast cells remains unclear. METHODS:
In this study, cell viability was analyzed using the MTT [3-(4,5-dimethylthiazol
2-yl)-2,5-diphenyltetrazolium bromide] assay. Cell cycle distribution was
analyzed by flow cytometer. The levels of transforming growth factor beta1,
vascular endothelial growth factor, and collagens were analyzed by enzyme-linked
immunosorbent assay and immunofluorescence staining. The expressions of cyclin A,
phosphorylation of extracellular signal-related kinase (p-ERK1/2), and ERK1/2
were analyzed by Western blotting. RESULTS: Our results showed that GTP promoted
cell proliferation and increased the percentage of cells in S phase through the
upregulation of cyclin A in NIH/3T3 cells. We also found that GTP induced the
secretion of type I collagen, and promoted the expression of other factors that
regulate the synthesis of collagen such as transforming growth factor beta1 and
vascular endothelial growth factor. In addition, the phosphorylation of ERK1/2 at
Thr202/Tyr204 was also increased by GTP. CONCLUSION: Our studies suggest that GTP
promoted proliferation and secretion of collagen in NIH/3T3 cells by activating
the ERK signal pathway, which shed light on a potential function of GTP in
promoting wound healing.
PMID- 28701886
TI - Overexpression of ginseng UGT72AL1 causes organ fusion in the axillary leaf
branch of Arabidopsis.
AB - BACKGROUND: Glycosylation of natural compounds increases the diversity of
secondary metabolites. Glycosylation steps are implicated not only in plant
growth and development, but also in plant defense responses. Although the
activities of uridine-dependent glycosyltransferases (UGTs) have long been
recognized, and genes encoding them in several higher plants have been
identified, the specific functions of UGTs in planta remain largely unknown.
METHODS: Spatial and temporal patterns of gene expression were analyzed by
quantitative reverse transcription (qRT)-polymerase chain reaction (PCR) and GUS
histochemical assay. In planta transformation in heterologous Arabidopsis was
generated by floral dipping using Agrobacterium tumefaciens (C58C1). Protein
localization was analyzed by confocal microscopy via fluorescent protein tagging.
RESULTS: PgUGT72AL1 was highly expressed in the rhizome, upper root, and youngest
leaf compared with the other organs. GUS staining of the promoter: GUS fusion
revealed high expression in different organs, including axillary leaf branch.
Overexpression of PgUGT72AL1 resulted in a fused organ in the axillary leaf
branch. CONCLUSION: PgUGT72AL1, which is phylogenetically close to PgUGT71A27, is
involved in the production of ginsenoside compound K. Considering that compound K
is not reported in raw ginseng material, further characterization of this gene
may shed light on the biological function of ginsenosides in ginseng plant growth
and development. The organ fusion phenotype could be caused by the defective
growth of cells in the boundary region, commonly regulated by phytohormones such
as auxins or brassinosteroids, and requires further analysis.
PMID- 28701887
TI - Quality and characteristics of fermented ginseng seed oil based on bacterial
strain and extraction method.
AB - BACKGROUND: In this study, the fermentation of ginseng seeds was hypothesized to
produce useful physiologically-active substances, similar to that observed for
fermented ginseng root. Ginseng seed was fermented using Bacillus, Pediococcus,
and Lactobacillus strains to extract ginseng seed oil, and the extraction yield,
color, and quantity of phenolic compounds, fatty acids, and phytosterol were then
analyzed. METHODS: The ginseng seed was fermented inoculating 1% of each strain
on sterilized ginseng seeds and incubating the seeds at 30 degrees C for 24 h.
Oil was extracted from the fermented ginseng seeds using compression extraction,
solvent extraction, and supercritical fluid extraction. RESULTS AND CONCLUSION:
The color of the fermented ginseng seed oil did not differ greatly according to
the fermentation or extraction method. The highest phenolic compound content
recovered with the use of supercritical fluid extraction combined with
fermentation using the Bacillus subtilis Korea Food Research Institute (KFRI)
1127 strain. The fatty acid composition did not differ greatly according to
fermentation strain and extraction method. The phytosterol content of ginseng
seed oil fermented with Bacillus subtilis KFRI 1127 and extracted using the
supercritical fluid method was highest at 983.58 mg/100 g. Therefore, our results
suggested that the ginseng seed oil fermented with Bacillus subtilis KFRI 1127
and extracted using the supercritical fluid method can yield a higher content of
bioactive ingredients, such as phenolics, and phytosterols, without impacting the
color or fatty acid composition of the product.
PMID- 28701888
TI - Pharmacological Treatment of Heart Failure with Preserved Ejection Fraction.
AB - Heart failure with preserved ejection fraction is a socioeconomic burden in Japan
as well as other developed countries. Diuretics are widely used to attenuate
symptoms and signs of congestion in both heart failure with preserved and reduced
ejection fraction, although their effects on long-term prognosis of both
phenotypes of heart failure have not been demonstrated because of an ethical
difficulty in designing a randomized and prospective clinical trial. Guidelines
do not provide any guidance on therapy choice, and physicians blindly choose
furosemide among loop diuretics in current clinical settings. However, several
clinical studies have suggested that the effects of loop diuretics are not
consistent, and that furosemide is not necessarily preferable as compared with
other loop diuretics. We should pay attention to the choice of loop diuretics.
Regarding the improvement of long-term prognosis, angiotensin-converting enzyme
inhibitor/angiotensin receptor blocker, mineralocorticoid receptor blocker and
beta-blocker are proven effective for heart failure with reduced ejection
fraction. However, none of these drugs have improved prognosis of heart failure
with preserved ejection fraction in clinical trials. Observational studies and
subanalysis of clinical trials suggest the benefits of these drugs in this
phenotype of heart failure. All of clinical trials and observational studies
present facts to us, and let us recognize that "one size fits all approach" may
be a cause for a lack of evidence about the therapeutic strategy of heart failure
with preserved ejection fraction until now. We have to make efforts to clarify
characteristics of patients with heart failure and preserved ejection fraction to
whom the administration of each drug provides benefits or do not.
PMID- 28701889
TI - Education for Community-based Family Medicine: A Social Need in the Real World.
AB - One of the most critical social problems in Japan is the remarkable increase in
the aging population. Elderly patients with a variety of complications and issues
other than biomedical problems such as dementia and life support with nursing
care have been also increasing. Ever since the Japanese economy started to
decline after the economic bubble burst of 1991 and the Lehman Brothers
bankruptcy in 2008, how we can resolve health problems of the elderly at a lower
cost has become one of our most challenging social issues. On the other hand, the
appropriate supply of medical and welfare resources is also a fundamental
problem. The disparity of physician distribution leads to a marked lack of
medical services especially in remote and rural areas of Japan. The government
has been attempting to recruit physicians into rural areas through a regional
quota system. Based on this background, the medical field pays a great amount of
attention to community-based family medicine (CBFM). CBFM requires basic
knowledge of community health and family medicine. The main people involved in
CBFM are expected to be a new type of general practitioner that cares for
residents in targeted communities. To improve the performance of CBFM doctors, we
need to establish a better CBFM education system and assess it appropriately when
needed. Here, we review the background of CBFM development and propose an
effective education system.
PMID- 28701890
TI - Relationship between Oxidative Stress, Physical Activity, and Vitamin Intake in
Patients with Asthma.
AB - BACKGROUND: Oxidative stress plays an important role in the pathogenesis of
bronchial asthma. Antioxidant nutrition and supplementation have been used to
reduce oxidative stress. However, a clinical trial with antioxidant
supplementation showed no beneficial effects in patients with asthma. On the
other hand, physical activity is related to the prognosis of chronic obstructive
pulmonary disease (COPD) and is also related to oxidant status. We investigated
the relationships between oxidative stress, serum levels of vitamins, dietary
vitamin intake, daily activities, and pulmonary functions in patients with
asthma. METHODS: Eighteen patients with bronchial asthma were enrolled in this
study. Reactive oxidative stress was assessed by measuring organic hydroperoxides
(diacron reactive oxygen metabolites: dROM) in sera and by measuring H2O2 levels
in exhaled breath condensates. The biological antioxidant capacity in serum was
evaluated by measuring antioxidant potential capacity against ferric ion. We also
assessed pulmonary functions, fraction of exhaled nitric oxide, serum levels of
vitamins, dietary vitamin intake, and physical activities. RESULTS: There were no
relationships between the index of oxidative stress (dROM and H2O2 in exhaled
breathe condensates) and pulmonary functions, serum levels of vitamins, daily
vitamin intakes, and activity levels in patients with asthma. CONCLUSION: The
status of transient oxidative stress may not be related to daily activities,
vitamin levels, and pulmonary functions in patients with asthma in a real-life
setting. However, our results were obtained in the short-term period from a small
number of subjects, so a large longitudinal study is required to ascertain the
relationships between oxidative stress, physical activity and vitamin intake in
patients with asthma.
PMID- 28701891
TI - Comprehensive Analysis of Factors Affecting Post-partial Nephrectomy Renal Global
Function.
AB - BACKGROUND: To explore new factors that are predictive of post-partial
nephrectomy (PN) renal global function, we analyzed various clinico-pathological
factors with a special focus on renal volume measured via three-dimensional
imaging technology and histopathological parameters in non-neoplastic parenchyma.
METHODS: Estimated glomerular filtration rate (eGFR) and computed tomography (CT)
scan were examined pre- and 6 months. post-operatively in 52 patients treated by
PN. The post-operative percent eGFR decline was employed as the measure of global
renal functional deterioration. The novel factors analyzed included the percent
renal parenchymal volume decline of the diseased side, contralateral and
bilateral sides and the global glomerulosclerosis (GS) extent in non-neoplastic
parenchyma. Renal parenchymal volumetry by CT scan was performed using SYNAPSE
VINCENT (Fujifilm). Additional factors analyzed included patient demographics and
comorbidities, surgical factors and tumor pathology. All factors demonstrating
significant tendencies (P < 0.1) in univariate analyses were subjected to
multivariate logistic regression analysis. RESULTS: Two groups were categorized
according to the degree of eGFR decline. Groups A and B were categorized as less
than 15% and greater than 15% decline, respectively. Pre-operative eGFR was
significantly lower in group B than in group A. Greater than 10% global GS extent
in non-neoplastic parenchyma, male gender and proteinuria were significantly more
frequent in in group B than in group A. The renal volume change was not
statistically significant. In multivariate logistic regression analysis, greater
than 10% global GS extent in non-neoplastic parenchyma was the sole independent
affecting factor for Group B. CONCLUSION: Our study suggested that host factors
rather than surgical factors may be useful for the prediction of post-PN renal
global function. The evaluation of the global GS extent in non-neoplastic
parenchyma is a promising biomarker of post-PN renal global function.
PMID- 28701892
TI - A Pilot Study of Post-Operative Adjuvant Vaccine for Advanced Gastric Cancer.
AB - BACKGROUND: Previously, we had performed a clinical study using human leukocyte
antigen (HLA)-A24-binding peptide vaccines containing a combination of novel
cancer-testis antigens and anti-angiogenic peptides derived from DEPDC1, URLC10,
FOXM1, KIF20A and VEGFR1 for advanced gastric cancer (AGC) patients who were
refractory to chemotherapy. We applied the cocktail vaccine to the combination
therapy with S-1 for patients with AGC as a post-operative adjuvant therapy and
performed this clinical pilot study. METHODS: AGC patients who had curative
surgery and were classified as pathologically stage III were enrolled. At each 6
week treatment cycle, patients received weekly subcutaneous administration of the
cocktail vaccine with 5 continuous injections and one break for the first 4
cycles and with bi-weekly injections for the following 4 cycles. S-1 (80 mg/m2)
was administered orally for 4 weeks with 2-week rest for all 8 cycles. The
primary endpoint was the safety of the combination therapy and the secondary was
the relative dose intensity for S-1. RESULTS: Fourteen patients were enrolled.
Six patients with HLA-A*2402 had received S-1 plus the cocktail vaccine as an
adjuvant therapy and the remaining 8 had S-1 monotherapy for eight cycles. Five
out of 6 patients subjected to the combination group completed the therapy and
one patient discontinued because of Grade 3 injection-site reaction. No adverse
events of grade 3 or higher were observed except injection-site reactions shown
in 5 out of 6 patients who had vaccine therapy. The mean and median relative dose
intensities for S-1 were 75.5% and 88% in the combination group and 67% and 80.5%
in S-1. CONCLUSION: The vaccine therapy combined with S-1 was manageable and safe
adjuvant therapy for stage III gastric cancer. Furthermore, the optimal relative
dose intensity of S-1 was achieved in combination group, although the injection
site reaction should be considered.
PMID- 28701893
TI - Risk Assessment of Hepatocellular Carcinoma in General Population by Liver
Stiffness in Combination with Controlled Attenuation Parameter using Transient
Elastography: A Cross Sectional Study.
AB - BACKGROUND: Hepatocellular carcinoma (HCC) in patients without hepatitis B (HBV)
and -C virus (HCV) infection are increasing in Japan. Method for detecting high
risk liver diseases of HCC in general population has still not been established.
Liver stiffness measurement (LSM) and Controlled Attenuation Parameter (CAP)
using transient elastography (TE; FibroScan System) are useful for detecting
liver fibrosis and steatosis. The aim of this study is to clarify TE for risk
assessment of HCC in general population. METHODS: This cross-sectional study was
performed for residents aged >= 40 years in an intermountain town in Japan with a
population of 3,493. Blood laboratory testing included tumor markers, abdominal
ultrasound (AUS), and TE was performed. RESULTS: Among 175 subjects (64 men, 111
women), TE was evaluated and three patients with HCC were detected by AUS. For
detecting HCC, the cut-off value of LSM was 5.3 kPa sensitivity 100%, specificity
75%, AUROC 0.88). The combination of LSM and CAP (LSM > 5.3 kPa with any CAP and
CAP > 248 dB/m with any LSM) could detect the high-risk liver diseases of HCC
(HCC, nonalcoholic fatty liver/steatohepatitis, HBV or HCV related chronic viral
hepatitis with alanine transaminase (ALT) > 30 IU/L for men or > 19 IU/L for
women or cirrhosis of any cause) with high sensitivity (sensitivity 90%,
specificity 55%, positive predictive value 10%, negative predictive value 99%, P
= 0.006). CONCLUSION: The combination of LSM and CAP can be useful in detecting
high-risk liver diseases of HCC out of general population.
PMID- 28701894
TI - Volume Measurement by Diffusion-Weighted Imaging in Cervical Cancer.
AB - BACKGROUND: The aim of this paper was to evaluate the validity of tumor volume
measurement using diffusion-weighted (DW) imaging in cervical cancer. METHODS: In
this retrospective study, 22 patients, who underwent preoperative 3.0 T MR
examinations with DW imaging were evaluated. Tumor volume measurement by oblique
axial (short axis to the uterine cervix) T2-weighted imaging was performed by
manually outlining the tumor on the monitor. The area of tumor in each slice was
multiplied by the slice profile (slice thickness plus intersection gap), and the
total tumor volume was calculated by summation of these obtained volumes.
Meanwhile, one experienced radiological technologist generated three-dimensional
DW images of cervical cancer using a volume-rendering algorithm at a computer
workstation, and tumor volume was automatically calculated in the workstation.
Analysis via the intraclass correlation coefficient (ICC) and Bland-Altman plots
were used to assess the validity and reliability of these methods. RESULTS:
Between tumor volumes measured by T2-weighted imaging methods and DW imaging
methods, the ICC was excellent (0.962). The 95% limits of agreement of volume
measurement were -52.7 and 35.7 mL (mean difference, -8.5 mL). In regards to
intra-observer variability, the ICC was excellent (0.963). The 95% limits of
agreement of volume measurement were -42.2 and 47.4 mL (mean difference, 2.6 mL).
CONCLUSION: DW imaging can be used to measure cervical cancer volume.
PMID- 28701895
TI - Decreased Serum Concentration of Total IgG Is Related to Tumor Progression in
Gastric Cancer Patients.
AB - BACKGROUND: There is accumulating evidence that shows cell-mediated immunity
regulated by T cells is impaired in cancer patients. Unfortunately, the
mechanisms by which B cells participate in tumor immunity are only partially
understood. METHODS: The serum concentration of Immunoglobulin G (IgG) was
measured by Enzyme-Linked ImmunoSorbent Assay (ELISA) in patients with gastric
cancer. Immunohistochemistry was also performed using the anti- cluster of
differentiation (CD)134 antibody to evaluate the number of plasma cells in the
tumor tissue. RESULTS: The total serum IgG concentration was significantly lower
in patients with lymph node metastasis compared with patients without metastasis.
The serum concentration of total IgG at stage III/IV was significantly lower
compared with tumors classified as stage I/II. A decreased serum concentration of
total IgG and IgG1 was significantly related to a poor prognosis for gastric
cancer patients. Furthermore, multivariate analysis indicated that the serum
concentration of IgG and lymph node metastasis were independent prognostic
indicators for poorer survival. The number of plasma cells was significantly
lower in gastric cancer tissue compared with non-cancerous gastric mucosa.
CONCLUSION: A decreased serum concentration of IgG was closely related to poor
prognosis, indicating the possibility that impaired antibody-mediated immunity is
associated with tumor progression in patients with gastric cancer.
PMID- 28701896
TI - Use of Body Mass Index to Predict the Prognosis of Patients with Remnant Gastric
Cancer.
AB - BACKGROUND: Remnant gastric cancer (RGC) is an uncommon form of gastric cancer.
The aim of this study was to investigate factors influencing the prognosis of
patients with RGC. METHODS: A total of 49 patients diagnosed with RGC and 214
patients with primary upper third gastric cancer (PUGC) at our institution
between January 1990 and December 2014 were included. The clinicopathological
characteristics, prognosis, and factors influencing prognosis were compared.
RESULTS: The body mass index (BMI) of RGC was significantly lower than that for
PUGC (P < 0.0001). Multivariate analysis revealed that BMI and the depth of tumor
invasion were independent prognostic factors in RGC. ROC analysis indicated that
an optimal cut-off value for BMI was 20.6. Based on this value, patients were
divided into two groups: BMIHigh (>= 20.6) and BMILow (< 20.6). The 5-year
survival rates of patients with BMIHigh early gastric cancer, BMIHigh advanced
gastric cancer, BMILow early gastric cancer, and BMILow advanced gastric cancer
were 90%, 83.3%, 64.3% and 33.8%, respectively, and the difference was
statistically significant (P = 0.00023). CONCLUSION: Our retrospective study
indicated a poor prognosis of RGC compared with PUGC, and that BMI could predict
the prognosis of RGC. The prognosis of patients with BMILow advanced RGC was
extremely poor.
PMID- 28701897
TI - Usefulness of Pulse Oximeter That Can Measure SpO2 to One Digit After Decimal
Point.
AB - Pulse oximeters are used to noninvasively measure oxygen saturation in arterial
blood (SaO2). Although arterial oxygen saturation measured by pulse oximeter
(SpO2) is usually indicated in 1% increments, the value of SaO2 from arterial
blood gas analysis is not an integer. We have developed a new pulse oximeter that
can measure SpO2 to one digit after the decimal point. The values of SpO2 from
the newly developed pulse oximeter are highly correlated with the values of SaO2
from arterial blood gas analysis (SpO2 = 0.899 * SaO2 + 9.944, r = 0.887, P <
0.0001). This device may help improve the evaluation of pathological conditions
in patients.
PMID- 28701898
TI - Aspects of family caregiving as addressed in planned discussions between nurses,
patients with chronic diseases and family caregivers: a qualitative content
analysis.
AB - BACKGROUND: Caregiving by family members of elderly with chronic conditions is
currently intensifying in the context of an aging population and health care
reform in the Netherlands. It is essential that nurses have attention for
supporting roles of family caregivers of older patients and address family
caregiving aspects on behalf of the continuity of care. This study aims to
explore what aspects of family caregiving were addressed during planned
discussions between nurses, patients and family caregivers in the hospital.
METHODS: Qualitative descriptive research was conducted using non-participant
observation and audio-recordings of planned discussions between nurses, older
patients and their family caregivers as they took place in the hospital. Through
purposive sampling eligible patients (>= 65 years) with one or more chronic
conditions were included. These patients were admitted to the hospital for
diagnostics or due to consequences of their chronic illness. Retrospective chart
review was done to obtain patient characteristics. Data were collected in
November/December 2013 and April/May 2014 in four hospitals. Qualitative content
analysis was performed using the inductive approach in order to gain insight into
addressed aspects of family caregiving. RESULTS: A total of 62 patients (mean age
(SD) 76 years (7.2), 52% male) were included in the study, resulting in 146
planned discussions (62 admission and discharge discussions and 22 family
meetings). Three themes were identified regarding addressed aspects of family
caregiving. Two themes referred to aspects addressing the patients' social
network, and included 'social network structure' and 'social network support'.
One theme referred to aspects addressing coordination of care issues involving
family caregiving, referred to as 'coordination of care'. CONCLUSIONS: During
discussions nurses mostly addressed practical information on the patients' social
network structure. When specific family caregiving support was addressed,
information was limited and nurses did not seem to explore the nature of the
family support. Patients discharge and after care needs were addressed
occasionally as aspects of coordination of care. Current nursing policies could
be evaluated on nursing and family oriented theories. Implications for education
could include mirroring study findings with nurses in a group discussion to
enhance their awareness on family caregiving aspects.
PMID- 28701899
TI - Cost-effectiveness analysis of the nine-valent HPV vaccine in Italy.
AB - BACKGROUND: In Italy HPV vaccination with the quadrivalent vaccine (Gardasil(r))
is offered actively and free of charge to girls aged 12 since 2007. A nine-valent
vaccine (Gardasil 9(r)) received the European market authorization in 2015 to
protect, with only 2 doses, against around 90% of all HPV positive cancers, over
80% of high-grade precancerous lesions and 90% of genital warts caused by HPV
types 6/11. METHODS: A dynamic transmission model simulating the natural history
of HPV-infections was calibrated to the Italian setting and used to estimate
costs and QALYs associated with vaccination strategies. The analyses compared two
strategies with the nine-valent vaccine (cervical cancer screening and
vaccination in girls only or vaccination in boys and girls) to four alternative
strategies (cervical cancer screening and vaccination with quadrialent vaccine in
girls only, in both boys and girls, with bivalent vaccine in girls and screening
strategy only). The National Health Service perspective was considered.
CONCLUSION: The switch to the nine-valent vaccine in Italy can further reduce the
burden associated to cervical cancer and HPV-related diseases and is highly cost
effective. RESULTS: Compared to the current vaccination program with quadrivalent
vaccine, the nine-valent vaccine in a programme including girls and boys shows
further reductions of 17% in the incidence of cervical cancer, 35 and 14% in anal
cancer for males and females, as well as over a million cases of genital warts
avoided after 100 years. The new technology is associated with an ICER of 10,463?
per QALY gained in universal vaccination, decreasing to 4483? when considering
the vaccine switch for girls-only.
PMID- 28701900
TI - Selection of patients with left breast cancer for deep-inspiration breath-hold
radiotherapy technique: Results of a prospective study.
AB - AIM: To assess prospectively which patients with left breast cancer have the
dosimetric benefit from the use of deep-inspiration breath-hold radiotherapy
(DIBH-RT). BACKGROUND: Improvement in selection of patients for DIBH-RT would
spare time of radiotherapy staff by removing the need for preparation of two
comparative treatment plans. MATERIALS AND METHODS: Thirty-one patients qualified
for whole left breast irradiation underwent breath-hold training and their free
breathing (FB) and DIBH planning-CT were included in the analysis of dosimetric
outcome. Mean heart dose (MHD), heart V20 Gy (V20Heart), maximum dose to LAD
(LADmax), V20 for left lung (V20L.lung) were recorded from FB and DIBH plans and
the differences (Delta) of these values were calculated. If relative improvement
of at least 20% for any evaluated dosimetric parameter was found for the DIBH-RT,
this plan was selected for treatment. Correlations of Delta of dosimetric
parameters with patient-related parameters (BMI, age, PTV, cardiac contact
distance [CCD], lung volume at FB) were sought. RESULTS: In 30 of 31 patients, a
predefined reduction in evaluated parameters was achieved. CCD, BMI correlated
positively with DeltaMHD, DeltaV20Heart, DeltaLADmax; PTV with DeltaMHD and
DeltaV20Heart (p < 0.05; AUC > 0.6); Lung volume correlated negatively with
DeltaLADmax, DeltaMHD and DeltaV20Heart. No specific thresholds for the lack of
predefined improvement of any dosimetric parameters was identified in ROC
analysis. 19/30 (63%) patients with dosimetric benefit completed their RT with
DIBH. CONCLUSIONS: Despite a strong correlation between patient-related and
dosimetric parameters, we cannot use the anatomical characteristics' thresholds
to select patients for whom DIBH-RT will not be considered.
PMID- 28701901
TI - A Longitudinal Assessment of the Home Literacy Environment and Early Language.
AB - This longitudinal assessment concentrated on the relation between the Home
Literacy Environment (HLE) and early language acquisition during infancy and
toddlerhood. In Study 1, after controlling for SES, a broadly-defined HLE
predicted language comprehension in 50 infants. In Study 2, 27 children and their
primary caregivers returned for further analyses. Findings revealed that the HLE
measured in infancy predicted language production in toddlerhood, and maternal
redirecting behaviors measured in toddlerhood were negatively associated with
expressive language. Results across both studies indicate the importance of a
broadly-defined HLE (including joint attention and parent-child conversation) for
language development. Taken together, these findings highlight the importance of
the HLE in supporting both receptive and expressive vocabulary growth in the
second and third years of life.
PMID- 28701902
TI - Empathy-Related Responding in Chinese Toddlers: Factorial Structure and Cognitive
Contributors.
AB - The critical role of the second year of life in the development of empathy is
well accepted by psychologists. However, the developmental trends of the
different components of empathy and the potential factors underlying these
components during this critical period remain unclear. Eighty-four Chinese
toddlers in the second year of life participated in the present study. Empathy
related responses were observed during three simulated procedures performed by
each child's primary caregiver, the experimenter and a baby doll. An exploratory
factor analysis was used to identify the different components of empathy. The
shared representation of the self and others was measured using the Tasks for the
Observation of Self-Concept, self/other awareness was measured with a series of
mirror tests and inhibitory control was measured using the Cylinder Inhibitory
Control Task. The results showed that the empathy of Chinese toddlers contains
three factors: sympathy, personal distress and orientation. Potential cognitive
factors contribute to the different components of empathy through both
independent and joint effects.
PMID- 28701903
TI - An Embodiment Perspective on Number-Space Mapping in 3.5-Year-Old Dutch Children.
AB - Previous research suggests that block adding, subtracting and counting direction
are early forms of number-space mapping. In this study, an embodiment perspective
on these skills was taken. Embodiment theory assumes that cognition emerges
through sensory-motor interaction with the environment. In line with this
assumption, it was investigated if counting and adding/subtracting direction in
young children is related to the hand they use during task performance. Forty
eight 3.5-year-old children completed a block adding, subtracting and counting
task. They had to add and remove a block from a row of three blocks and count a
row of five blocks. Adding, subtracting and counting direction were related to
the hand the children used for task performance. Most children who used their
right hand added, removed and started counting the blocks at the right side of
the row. Most children who used their left hand added, removed and started
counting the blocks at the left side of the row. It can be concluded that number
space mapping, as measured by direction of adding, subtracting and counting
blocks, in young children is embodied: It is not fixed, but is related to the
situation.
PMID- 28701905
TI - Complexity of the Culex pipiens complex in California.
AB - In California, the Culex pipiens complex consists of Culex pipiens, Cx.
quinquefasciatus, their hybrids and Culex pipiens form molestus. Using 15
microsatellite markers and a variety of statistical analyses of within- and among
population variation, there is widespread introgression throughout the Central
Valley with mostly quinquefasciatus genotypes in the south and pipiens in the
north. Those specimens in the Sacramento County area consisted primarily of
pipiens-quinquefasciatus and pipiens-molestus hybrids. Populations in Coachella
Valley and Los Angeles, CA and Benton, WA were Cx. quinquefasciatus and Cx.
pipiens, respectively. Studies are underway to relate these genotypes to
phenotypes of autogeny, diapause and vector competence for West Nile Virus.
PMID- 28701904
TI - Medical and Behavioral Approaches to Engage People Who Inject Drugs Into Care for
Hepatitis C Virus Infection.
AB - Direct-acting antivirals for hepatitis C virus infection may revolutionize
treatment among persons with substance use disorders. Despite persons with
substance use disorders having the highest hepatitis C virus prevalence and
incidence, the vast majority have not engaged into care for the infection.
Previously, interferon-based treatments, with substantial side effects and the
propensity to exacerbate mental health conditions, were major disincentives to
pursuit of care for the infection. Direct-acting antivirals with viral
eradication rates of >90%, significantly improved side effect profiles, and
shorter treatment duration are dramatic improvements over prior treatment
regimens that should promote widespread hepatitis C virus care among persons with
substance use disorders. The major unmet need is strategies to promote persons
with substance use disorders engagement into care for hepatitis C virus. Although
physical integration of treatment for substance use and co-occurring conditions
has been widely advocated, it has been difficult to achieve. Telemedicine offers
an opportunity for virtual integration of behavioral and medical treatments that
could be supplemented by conventional interventions such as hepatitis C virus
education, case management, and peer navigation. Furthermore, harm reduction and
strategies to reduce viral transmission are important to cease reinfection among
persons with substance use disorders. Widespread prescription of therapy for
hepatitis C virus infection to substance users will be required to achieve the
ultimate goal of global virus elimination. Combinations of medical and behavioral
interventions should be used to promote persons with substance use disorders
engagement into and adherence with direct-acting antiviral-based treatment
approaches. Ultimately, either physical or virtual colocation of hepatitis C
virus and substance use treatment has the potential to improve adherence and
consequently treatment efficacy.
PMID- 28701906
TI - Proteomic discovery and verification of serum amyloid A as a predictor marker of
patients at risk of post-stroke infection: a pilot study.
AB - BACKGROUND: Post-stroke infections occur in 20-36% of stroke patients and are
associated with high morbidity and mortality rates. Early identification of
patients at risk of developing an infection could improve care via an earlier
treatment leading to a better outcome. We used proteomic tools in order to
discover biomarkers able to stratify patients at risk of post-stroke infection.
METHODS: The post hoc analysis of a prospective cohort study including 40
ischemic stroke patients included 21 infected and 19 non-infected participants. A
quantitative, isobaric labeling, proteomic strategy was applied to the plasma
samples of 5 infected and 5 non-infected patients in order to highlight any
significantly modulated proteins. A parallel reaction monitoring (PRM) assay was
applied to 20 additional patients (10 infected and 10 non-infected) to verify
discovery results. The most promising protein was pre-validated using an ELISA
immunoassay on 40 patients and at different time points after stroke onset.
RESULTS: Tandem mass analysis identified 266 proteins, of which only serum
amyloid A (SAA1/2) was significantly (p = 0.007) regulated between the two groups
of patients. This acute-phase protein appeared to be 2.2 times more abundant in
infected patients than in non-infected ones. These results were verified and
validated using PRM and ELISA immunoassays, which showed that infected patients
had significantly higher concentrations of SAA1/2 than non-infected patients at
hospital admission, but also at 1, 3, and 5 days after admission. CONCLUSIONS:
The present study demonstrated that SAA1/2 is a promising predictor, at hospital
admission, of stroke patients at risk of developing an infection. Further large,
multicenter validation studies are needed to confirm these results. If confirmed,
SAA1/2 concentrations could be used to identify the patients most at risk of post
stroke infections and therefore implement treatments more rapidly, thus reducing
mortality.
PMID- 28701908
TI - Total Synthesis of Viniferifuran, Resveratrol-Piceatannol Hybrid, Anigopreissin A
and Analogues - Investigation of Demethylation Strategies.
AB - Resveratrol-based natural products constitute a valuable source of unique
compounds with diverse biological activities. In this report we investigate
demethylation strategies to minimize formation of cyclized and dimerized products
during the synthesis of viniferifuran and analogues. We found that boron
trichloride/tetra-n-butylammonium iodide (BCl3/TBAI) is typically more effective
than boron tribromide (BBr3). Based on these findings we carried out the first
syntheses of dehydro-delta-viniferin, resveratrol-piceatannol hybrid and
anigopreissin A. In addition, we have developed a short and efficient route to
viniferifuran that was obtained in 13% yield over six steps.
PMID- 28701907
TI - Adaptation of human skin color in various populations.
AB - BACKGROUND: Skin color is a well-recognized adaptive trait and has been studied
extensively in humans. Understanding the genetic basis of adaptation of skin
color in various populations has many implications in human evolution and
medicine. DISCUSSION: Impressive progress has been made recently to identify
genes associated with skin color variation in a wide range of geographical and
temporal populations. In this review, we discuss what is currently known about
the genetics of skin color variation. We enumerated several cases of skin color
adaptation in global modern humans and archaic hominins, and illustrated why,
when, and how skin color adaptation occurred in different populations. Finally,
we provided a summary of the candidate loci associated with pigmentation, which
could be a valuable reference for further evolutionary and medical studies.
CONCLUSION: Previous studies generally indicated a complex genetic mechanism
underlying the skin color variation, expanding our understanding of the role of
population demographic history and natural selection in shaping genetic and
phenotypic diversity in humans. Future work is needed to dissect the genetic
architecture of skin color adaptation in numerous ethnic minority groups around
the world, which remains relatively obscure compared with that of major
continental groups, and to unravel the exact genetic basis of skin color
adaptation.
PMID- 28701909
TI - Biogenic calcite particles from microalgae-Coccoliths as a potential raw
material.
AB - Synthetic calcite (CaCO3) particles are found in a broad range of applications.
The geometry of particles produced from limestone or precipitation are versatile
but limited to basic shapes. The microalga Emiliania huxleyi produces micro
structured calcite platelets, called coccoliths. This article presents the
results of an application-orientated study, which includes characteristic values
also used in the calcite industry for particle evaluation. It is demonstrated
that coccoliths are significantly different from all industrial particles
produced so far. Coccoliths are porous particles, mainly consisted of calcium
carbonate, with further elements such as Mg, Si, Sr, and Fe often embedded in
their structure. Their structure is extremely sophisticated, while the overall
particle morphology and particle size distribution are homogeneous. This study
gives a first inside into the potential of these exceptional objects and may set
further impulses for their utilization in specific calcite particle applications.
PMID- 28701911
TI - An Event-Driven Classifier for Spiking Neural Networks Fed with Synthetic or
Dynamic Vision Sensor Data.
AB - This paper introduces a novel methodology for training an event-driven classifier
within a Spiking Neural Network (SNN) System capable of yielding good
classification results when using both synthetic input data and real data
captured from Dynamic Vision Sensor (DVS) chips. The proposed supervised method
uses the spiking activity provided by an arbitrary topology of prior SNN layers
to build histograms and train the classifier in the frame domain using the
stochastic gradient descent algorithm. In addition, this approach can cope with
leaky integrate-and-fire neuron models within the SNN, a desirable feature for
real-world SNN applications, where neural activation must fade away after some
time in the absence of inputs. Consequently, this way of building histograms
captures the dynamics of spikes immediately before the classifier. We tested our
method on the MNIST data set using different synthetic encodings and real DVS
sensory data sets such as N-MNIST, MNIST-DVS, and Poker-DVS using the same
network topology and feature maps. We demonstrate the effectiveness of our
approach by achieving the highest classification accuracy reported on the N-MNIST
(97.77%) and Poker-DVS (100%) real DVS data sets to date with a spiking
convolutional network. Moreover, by using the proposed method we were able to
retrain the output layer of a previously reported spiking neural network and
increase its performance by 2%, suggesting that the proposed classifier can be
used as the output layer in works where features are extracted using unsupervised
spike-based learning methods. In addition, we also analyze SNN performance
figures such as total event activity and network latencies, which are relevant
for eventual hardware implementations. In summary, the paper aggregates
unsupervised-trained SNNs with a supervised-trained SNN classifier, combining and
applying them to heterogeneous sets of benchmarks, both synthetic and from real
DVS chips.
PMID- 28701910
TI - The Impact of Ecological Niche on Adaptive Flexibility of Sensory Circuitry.
AB - Evolution and development are interdependent, particularly with regard to the
construction of the nervous system and its position as the machine that produces
behavior. On the one hand, the processes directing development and plasticity of
the brain provide avenues through which natural selection can sculpt neural cell
fate and connectivity, and on the other hand, they are themselves subject to
selection pressure. For example, mutations that produce heritable perturbations
in neuronal birth and death rates, transcription factor expression, or
availability of axon guidance factors within sensory pathways can markedly affect
the development of form and thus the function of stimulus decoding circuitry.
This evolvability of flexible circuits makes them more adaptable to environmental
variation. Although there is general agreement on this point, whether the
sensitivity of circuits to environmental influence and the mechanisms underlying
development and plasticity of sensory pathways are similar across species from
different ecological niches has received almost no attention. Neural circuits are
generally more sensitive to environmental influences during an early critical
period, but not all niches afford the same access to stimuli in early life.
Furthermore, depending on predictability of the habitat and ecological niche,
sensory coding circuits might be more susceptible to sensory experience in some
species than in others. Despite decades of work on understanding the mechanisms
underlying critical period plasticity, the importance of ecological niche in
visual pathway development has received little attention. Here, I will explore
the relationship between critical period plasticity and ecological niche in
mammalian sensory pathways.
PMID- 28701912
TI - Brain Responses to a 6-Hz Binaural Beat: Effects on General Theta Rhythm and
Frontal Midline Theta Activity.
AB - A binaural beat is a beat phenomenon that is generated by the dichotic
presentation of two almost equivalent pure tones but with slightly different
frequencies. The brain responses to binaural beats remain controversial;
therefore, the aim of this study was to investigate theta activity responses to a
binaural beat by controlling factors affecting localization, including beat
frequency, carrier tone frequency, exposure duration, and recording procedure.
Exposure to a 6-Hz binaural beat on a 250 Hz carrier tone for 30 min was utilized
in this study. Quantitative electroencephalography (QEEG) was utilized as the
recording modality. Twenty-eight participants were divided into experimental and
control groups. Emotional states were evaluated by Brunel Mood Scale (BRMUS)
before and after exposing to the stimulus. The results showed that theta activity
was induced in the entire cortex within 10 min of exposure to the stimulus in the
experimental group. Compared to the control group, theta activity was also
induced at the frontal and parietal-central regions, which included the Fz
position, and left hemisphere dominance was presented for other exposure
durations. The pattern recorded for 10 min of exposure appeared to be brain
functions of a meditative state. Moreover, tension factor of BRUMS was decreased
in experimental group compared to control group which resembled the meditation
effect. Thus, a 6-Hz binaural beat on a 250 Hz carrier tone was suggested as a
stimulus for inducing a meditative state.
PMID- 28701913
TI - Common Hepatic Branch of Vagus Nerve-Dependent Expression of Immediate Early
Genes in the Mouse Brain by Intraportal L-Arginine: Comparison with
Cholecystokinin-8.
AB - Information from the peripheral organs is thought to be transmitted to the brain
by humoral factors and neurons such as afferent vagal or spinal nerves. The
common hepatic branch of the vagus (CHBV) is one of the main vagus nerve
branches, and consists of heterogeneous neuronal fibers that innervate multiple
peripheral organs such as the bile duct, portal vein, paraganglia, and
gastroduodenal tract. Although, previous studies suggested that the CHBV has a
pivotal role in transmitting information on the status of the liver to the brain,
the details of its central projections remain unknown. The purpose of the present
study was to investigate the brain regions activated by the CHBV. For this
purpose, we injected L-arginine or anorexia-associated peptide cholecystokinin-8
(CCK), which are known to increase CHBV electrical activity, into the portal vein
of transgenic Arc-dVenus mice expressing the fluorescent protein Venus under
control of the activity-regulated cytoskeleton-associated protein (Arc) promotor.
The brain slices were prepared from these mice and the number of Venus positive
cells in the slices was counted. After that, c-Fos expression in these slices was
analyzed by immunohistochemistry using the avidin-biotin-peroxidase complex
method. Intraportal administration of L-arginine increased the number of Venus
positive or c-Fos positive cells in the insular cortex. This action of L-arginine
was not observed in CHBV-vagotomized Arc-dVenus mice. In contrast, intraportal
administration of CCK did not increase the number of c-Fos positive or Venus
positive cells in the insular cortex. Intraportal CCK induced c-Fos expression in
the dorsomedial hypothalamus, while intraportal L-arginine did not. This action
of CCK was abolished by CHBV vagotomy. Intraportal L-arginine reduced, while
intraportal CCK increased, the number of c-Fos positive cells in the nucleus
tractus solitarii in a CHBV-dependent manner. The present results suggest that
the CHBV can activate different brain regions depending on the nature of the
peripheral stimulus.
PMID- 28701914
TI - Reduced Prefrontal Cortex Activation in Children with Attention
Deficit/Hyperactivity Disorder during Go/No-Go Task: A Functional Near-Infrared
Spectroscopy Study.
AB - Objective: Attention-deficit/hyperactivity disorder (ADHD) is one of the most
common neuropsychiatric disorders in children and affects 3 to 5% of school-aged
children. This study is to demonstrate whether functional near-infrared
spectroscopy (fNIRS) can detect the changes in the concentration of oxygenated
hemoglobin (oxy-HB) in children with ADHD and typically developing children (TD
children). Method: In this study, 14 children with ADHD and 15 TD children were
studied. Metabolic signals of functional blood oxygen were recorded by using
fNIRS during go/no-go task. A statistic method is used to compare the fNIRS
between the ADHD children and controls. Results: A significant oxy-HB increase in
the left frontopolar cortex (FPC) in control subjects but not in children with
ADHD during inhibitory tasks. Moreover, ADHD children showed reduced activation
in left FPC relative to TD children. Conclusion: Functional brain imaging using
fNIRS showed reduced activation in the left prefrontal cortex (PFC) of children
with ADHD during the inhibition task. The fNIRS could be a promising tool for
differentiating children with ADHD and TD children.
PMID- 28701915
TI - Web Camera Based Eye Tracking to Assess Visual Memory on a Visual Paired
Comparison Task.
AB - Background: Web cameras are increasingly part of the standard hardware of most
smart devices. Eye movements can often provide a noninvasive "window on the
brain," and the recording of eye movements using web cameras is a burgeoning area
of research. Objective: This study investigated a novel methodology for
administering a visual paired comparison (VPC) decisional task using a web
camera.To further assess this method, we examined the correlation between a
standard eye-tracking camera automated scoring procedure [obtaining images at 60
frames per second (FPS)] and a manually scored procedure using a built-in laptop
web camera (obtaining images at 3 FPS). Methods: This was an observational study
of 54 clinically normal older adults.Subjects completed three in-clinic visits
with simultaneous recording of eye movements on a VPC decision task by a standard
eye tracker camera and a built-in laptop-based web camera. Inter-rater
reliability was analyzed using Siegel and Castellan's kappa formula. Pearson
correlations were used to investigate the correlation between VPC performance
using a standard eye tracker camera and a built-in web camera. Results: Strong
associations were observed on VPC mean novelty preference score between the 60
FPS eye tracker and 3 FPS built-in web camera at each of the three visits (r =
0.88-0.92). Inter-rater agreement of web camera scoring at each time point was
high (kappa = 0.81-0.88). There were strong relationships on VPC mean novelty
preference score between 10, 5, and 3 FPS training sets (r = 0.88-0.94).
Significantly fewer data quality issues were encountered using the built-in web
camera. Conclusions: Human scoring of a VPC decisional task using a built-in
laptop web camera correlated strongly with automated scoring of the same task
using a standard high frame rate eye tracker camera.While this method is not
suitable for eye tracking paradigms requiring the collection and analysis of fine
grained metrics, such as fixation points, built-in web cameras are a standard
feature of most smart devices (e.g., laptops, tablets, smart phones) and can be
effectively employed to track eye movements on decisional tasks with high
accuracy and minimal cost.
PMID- 28701916
TI - The Role of HOTAIR/miR-148b-3p/USF1 on Regulating the Permeability of BTB.
AB - Homeobox transcript antisense intergenic RNA (HOTAIR), as a long non-coding RNA
(lncRNA), has been considered to play critical roles in the biological properties
of various tumors. The purposes of this study were to investigate the role and
possible molecular mechanisms of HOTAIR in regulating the permeability of blood
tumor barrier (BTB) in vitro. Our present study elucidated that the expressions
of HOTAIR and upstream stimulatory factor 1 (USF1) was up-regulated, but miR-148b
3p was down-regulated in glioma microvascular endothelial cells (GECs). Knockdown
of HOTAIR could increase the permeability of BTB as well as down-regulated the
expressions of tight junction related proteins ZO-1, occludin, claudin-5, but up
regulated miR-148b-3p expressions in GECs. Meanwhile, dual-luciferase reporter
assays demonstrated that HOTAIR was a target RNA of miR-148b-3p. Furthermore,
overexpression of miR-148b-3p increased the permeability of BTB by down
regulating the expressions of tight junction related proteins and USF1 in GECs,
and vice versa. And further result revealed USF1 was a target of miR-148b-3p.
Silence of USF1 increased the permeability of BTB duo to their interaction with
the promoters of ZO-1, occludin, and claudin-5 in GECs. Taken together, our
finding indicated that knockdown of HOTAIR increased BTB permeability via binding
to miR-148b-3p, which further reducing tight junction related proteins in GECs by
targeting USF1. Thus, HOTAIR will attract more attention since it can serve as a
potential target of drug delivery across BTB and may provide novel strategies for
glioma treatment.
PMID- 28701917
TI - Distinct Features of Doublecortin as a Marker of Neuronal Migration and Its
Implications in Cancer Cell Mobility.
AB - Neuronal migration is a critical process in the development of the nervous
system. Defects in the migration of the neurons are associated with diseases like
lissencephaly, subcortical band heterotopia (SBH), and pachygyria. Doublecortin
(DCX) is an essential factor in neurogenesis and mutations in this protein
impairs neuronal migration leading to several pathological conditions. Although,
DCX is capable of modulating and stabilizing microtubules (MTs) to ensure
effective migration, the mechanisms involved in executing these functions remain
poorly understood. Meanwhile, there are existing gaps regarding the processes
that underlie tumor initiation and progression into cancer as well as the ability
to migrate and invade normal cells. Several studies suggest that DCX is involved
in cancer metastasis. Unstable interactions between DCX and MTs destabilizes
cytoskeletal organization leading to disorganized movements of cells, a process
which may be implicated in the uncontrolled migration of cancer cells. However,
the underlying mechanism is complex and require further clarification. Therefore,
exploring the importance and features known up to date about this molecule will
broaden our understanding and shed light on potential therapeutic approaches for
the associated neurological diseases. This review summarizes current knowledge
about DCX, its features, functions, and relationships with other proteins. We
also present an overview of its role in cancer cells and highlight the importance
of studying its gene mutations.
PMID- 28701918
TI - Striatal Transcriptome and Interactome Analysis of Shank3-overexpressing Mice
Reveals the Connectivity between Shank3 and mTORC1 Signaling.
AB - Mania causes symptoms of hyperactivity, impulsivity, elevated mood, reduced
anxiety and decreased need for sleep, which suggests that the dysfunction of the
striatum, a critical component of the brain motor and reward system, can be
causally associated with mania. However, detailed molecular pathophysiology
underlying the striatal dysfunction in mania remains largely unknown. In this
study, we aimed to identify the molecular pathways showing alterations in the
striatum of SH3 and multiple ankyrin repeat domains 3 (Shank3)-overexpressing
transgenic (TG) mice that display manic-like behaviors. The results of
transcriptome analysis suggested that mammalian target of rapamycin complex 1
(mTORC1) signaling may be the primary molecular signature altered in the Shank3
TG striatum. Indeed, we found that striatal mTORC1 activity, as measured by mTOR
S2448 phosphorylation, was significantly decreased in the Shank3 TG mice compared
to wild-type (WT) mice. To elucidate the potential underlying mechanism, we re
analyzed previously reported protein interactomes, and detected a high
connectivity between Shank3 and several upstream regulators of mTORC1, such as
tuberous sclerosis 1 (TSC1), TSC2 and Ras homolog enriched in striatum (Rhes),
via 94 common interactors that we denominated "Shank3-mTORC1 interactome". We
noticed that, among the 94 common interactors, 11 proteins were related to actin
filaments, the level of which was increased in the dorsal striatum of Shank3 TG
mice. Furthermore, we could co-immunoprecipitate Shank3, Rhes and Wiskott-Aldrich
syndrome protein family verprolin-homologous protein 1 (WAVE1) proteins from the
striatal lysate of Shank3 TG mice. By comparing with the gene sets of psychiatric
disorders, we also observed that the 94 proteins of Shank3-mTORC1 interactome
were significantly associated with bipolar disorder (BD). Altogether, our results
suggest a protein interaction-mediated connectivity between Shank3 and certain
upstream regulators of mTORC1 that might contribute to the abnormal striatal
mTORC1 activity and to the manic-like behaviors of Shank3 TG mice.
PMID- 28701919
TI - Amyloid-beta Impairs Vesicular Secretion in Neuronal and Astrocyte Peptidergic
Transmission.
AB - Regulated secretion of neuropeptides and neurotrophic factors critically
modulates function and plasticity of synapses and circuitries. It is believed
that rising amyloid-beta (Abeta) concentrations, synaptic dysfunction and network
disorganization underlie early phases of Alzheimer's disease (AD). Here, we
analyze the impact of soluble Abeta1-42 assemblies on peptidergic secretion in
cortical neurons and astrocytes. We show that neurons and astrocytes
differentially produce and release carboxypeptidase E (CPE) and secretogranin III
(SgIII), two dense-core vesicle (DCV) markers belonging to the regulated
secretory pathway. Importantly, Abeta1-42, but not scrambled Abeta1-42,
dramatically impairs basal and Ca2+-regulated secretions of endogenously produced
CPE and SgIII in cultured neurons and astrocytes. Additionally, KCl-evoked
secretion of the DCV cargo brain-derived neurotrophic factor (BDNF) is lowered by
Abeta1-42 administration, whereas glutamate release from synaptic vesicle (SVs)
remains unchanged. In agreement with cell culture results, Abeta1-42 effects on
CPE and SgIII secretion are faithfully recapitulated in acute adult brain slices.
These results demonstrate that neuronal and astrocyte secretion of DCV cargos is
impaired by Abeta in vitro and in situ. Furthermore, Abeta-induced dysregulated
peptidergic transmission could have an important role in the pathogenesis of AD
and DCV cargos are possible candidates as cerebrospinal fluid (CSF) biomarkers.
PMID- 28701920
TI - Tlx3 Function in the Dorsal Root Ganglion is Pivotal to Itch and Pain Sensations.
AB - Itch, a sensation eliciting a desire to scratch, is distinct from but not
completely independent of pain. Inspiring achievements have been made in the
characterization of itch-related receptors and neurotransmitters, but the
molecular mechanisms controlling the development of pruriceptors remain poorly
understood. Here, our RNAseq and in situ hybridization data show that the
transcription factor Tlx3 is required for the expression of a majority of itch
related molecules in the dorsal root ganglion (DRG). As a result, Tlx3F/F;Nav1.8
cre mice exhibit significantly attenuated acute and dry skin-induced chronic
itch. Furthermore, our study indicates that TRPV1 plays a pivotal role in the
chronic itch evoked by dry skin and allergic contact dermatitis (ACD). The
mutants also display impaired response to cold and inflammatory pain and elevated
response to capsaicin, whereas the responses to acute mechanical, thermal stimuli
and neuropathic pain remain normal. In Tlx3F/F;Nav1.8-cre mice, TRPV1 is
derepressed and expands predominantly into IB4+ non-peptidergic (NP) neurons.
Collectively, our data reveal a molecular mechanism in regulating the development
of pruriceptors and controlling itch and pain sensations.
PMID- 28701921
TI - Endothelial-Monocyte Activating Polypeptide II Suppresses the In Vitro
Glioblastoma-Induced Angiogenesis by Inducing Autophagy.
AB - The obstacle in delivering therapeutics to glioblastoma (GBM) is tumor-induced
angiogenesis which leads to the formation of abnormal vessels and a dysfunctional
blood-tumor barrier. Here, we elucidated the effect of endothelial-monocyte
activating polypeptide II (EMAP II) on the GBM-induced angiogenesis as well as
its potential mechanisms. Our results proved that EMAP II inhibited the
viability, mitochondrial membrane potential, migration and tube formation of GBM
induced endothelial cells (GECs) by inducing cell autophagy, demonstrated by cell
viability assay, JC-1 staining assay, transwell assay and tube formation assay,
respectively. Cell autophagy was induced by EMAP II through the observation of
autophagic vacuoles formation and the up-regulation of microtubule-associated
protein-1 light chain-3 (LC3)-II and p62/SQSTM1 expression, demonstrated by
transmission electron microscopy analysis, immunofluorescence assay and Western
blot assay. The activity of PI3K/AKT/mTOR signal pathway could be inhibited by
the EMAP II treatment. Furthermore, unfolded protein response (UPR)-related
proteins (GRP78, eIF2alpha, and CHOP) were up-regulated by EMAP II, which suggest
that GECs exposed to EMAP II experienced endoplasmic reticulum stress. Further,
mechanistic investigations found that EMAP II reduced the miR-96 expression which
could directly target the 3'-UTR of these UPR-related proteins, and over
expression of miR-96 inhibited LC3 and p62/SQSTM1 expression by down-regulating
these UPR-related proteins in GECs. Moreover, the combination of EMAP II with miR
96 inhibitor showed the inhibitory effect on the viability, migration, and in
vitro tube formation of GECs, which are critical for angiogenesis. Taken
together, we have demonstrated the fact that EMAP II resulted in the decreased
GBM-induced angiogenesis by inducing autophagy, which might contribute to
establishing potential strategies for human GBM treatment.
PMID- 28701922
TI - Bone Marrow Mesenchymal Stem-Cell Transplantation Promotes Functional Improvement
Associated with CNTF-STAT3 Activation after Hemi-Sectioned Spinal Cord Injury in
Tree Shrews.
AB - Hemi-sectioned spinal cord injury (hSCI) can lead to spastic paralysis on the
injured side, as well as flaccid paralysis on the contralateral side, which can
negatively affect a patient's daily life. Stem-cell therapy may offer an
effective treatment option for individuals with hSCI. To examine the role of bone
marrow mesenchymal stem cells (BMSCs) transplantation on hSCI and explore related
mechanisms in the tree shrews, here, we created a model of hSCI by inducing
injury at the tenth thoracic vertebra (T10). Hoechst 33342-labeled BMSCs derived
from adult tree shrews were isolated, cultured, and implanted into the spinal
cord around the injury site at 9 days after injury. The isolated BMSCs were able
to survive, proliferate and release a variety of neurotrophic factors (NTFs) both
in vitro and in vivo. At 28 days after injury, compared with the sham group, the
hSCI group displayed scar formation and dramatic elevations in the mean
interleukin 1 beta (IL-1beta) density and cell apoptosis level, whereas the
expression of signal transducer and activator of transcription 3 (STAT3) and
ciliary neurotrophic factor (CNTF) mRNA was reduced. Following BMSC
transplantation, motoneurons extent of shrinkage were reduced and the animals'
Basso, Beattie, and Bresnahan (BBB) locomotion scale scores were significantly
higher at 21 and 28 days after injury when compared with the injured group.
Moreover, the hSCI-induced elevations in scar formation, IL-1beta, and cell
apoptosis were reduced by BMSC transplantation to levels that were close to those
of the sham group. Corresponding elevations in the expression of STAT3 and CNTF
mRNA were observed in the hSCI + BMSCs group, and the levels were not
significantly different from those observed in the sham group. Together, our
results support that grafted BMSCs can significantly improve locomotor function
in tree shrews subjected to hSCI and that this improvement is associated with the
upregulation of CNTF and STAT3 signaling.
PMID- 28701924
TI - Frontal Connectivity in EEG Gamma (30-45 Hz) Respond to Spinal Cord Stimulation
in Minimally Conscious State Patients.
AB - Spinal cord stimulation (SCS) has become a valuable brain-intervention technique
used to rehabilitate patients with disorders of consciousness (DOC). To explore
how the SCS affects the cerebral cortex and what possible electrophysiological
mechanism of SCS effects on the cortex, the present study investigated the
functional connectivity and network properties during SCS in minimally conscious
state (MCS) patients. MCS patients received both SCS and sham sessions.
Functional connectivity of the phase lock value (PLV) in the gamma band (30-45
Hz) was investigated at the pre-, on- and post-SCS stages. In addition, to
evaluate global network properties, complex network parameters, including average
path length, cluster coefficient and small-world, were measured. When SCS was
turned on, significantly decreased connectivity was noted in the local scale of
the frontal-frontal region and in the large scales of the frontal-parietal and
frontal-occipital regions. The global network showed fewer small-world
properties, average path lengths increased and cluster coefficients decreased.
When SCS was turned off, the large-scale connectivity and global network returned
to its pre-SCS level, but the local scale of frontal-frontal connectivity
remained significantly lower than its pre-SCS level. Sham sessions produced no
significant changes in either functional connectivity or network. The findings
directly showed that SCS could effectively intervene cortical gamma activity, and
the intervention included immediate global effects (large scale connectivity and
network alteration only occurred in stimulation period) and long-lasting local
effects (local scale connectivity alteration persist beyond stimulation period).
Moreover, considering the mechanism and propagation of gamma activity, it
indicates that the frontal cortex plays a crucial role in the SCS effects on the
cerebral cortex.
PMID- 28701923
TI - Cell Polarity in Cerebral Cortex Development-Cellular Architecture Shaped by
Biochemical Networks.
AB - The human cerebral cortex is the seat of our cognitive abilities and composed of
an extraordinary number of neurons, organized in six distinct layers. The
establishment of specific morphological and physiological features in individual
neurons needs to be regulated with high precision. Impairments in the sequential
developmental programs instructing corticogenesis lead to alterations in the
cortical cytoarchitecture which is thought to represent the major underlying
cause for several neurological disorders including neurodevelopmental and
psychiatric diseases. In this review article we discuss the role of cell polarity
at sequential stages during cortex development. We first provide an overview of
morphological cell polarity features in cortical neural stem cells and newly-born
postmitotic neurons. We then synthesize a conceptual molecular and biochemical
framework how cell polarity is established at the cellular level through a break
in symmetry in nascent cortical projection neurons. Lastly we provide a
perspective how the molecular mechanisms applying to single cells could be probed
and integrated in an in vivo and tissue-wide context.
PMID- 28701925
TI - Postsynaptic GABA(B) Receptors Contribute to the Termination of Giant
Depolarizing Potentials in CA3 Neonatal Rat Hippocampus.
AB - During development, hippocampal CA3 network generates recurrent population
bursts, so-called Giant Depolarizing Potentials (GDPs). GDPs are characterized by
synchronous depolarization and firing of CA3 pyramidal cells followed by
afterhyperpolarization (GDP-AHP). Here, we explored the properties of GDP-AHP in
CA3 pyramidal cells using gramicidin perforated patch clamp recordings from
neonatal rat hippocampal slices. We found that GDP-AHP occurs independently of
whether CA3 pyramidal cells fire action potentials (APs) or remain silent during
GDPs. However, the amplitude of GDP-AHP increased with the number of APs the
cells fired during GDPs. The reversal potential of the GDP-AHP was close to the
potassium equilibrium potential. During voltage-clamp recordings, current-voltage
relationships of the postsynaptic currents activated during GDP-AHP were
characterized by reversal near the potassium equilibrium potential and inward
rectification, similar to the responses evoked by the GABA(B) receptor agonists.
Finally, the GABA(B) receptor antagonist CGP55845 strongly reduced GDP-AHP and
prolonged GDPs, eventually transforming them to the interictal and ictal-like
discharges. Together, our findings suggest that the GDP-AHP involves two
mechanisms: (i) postsynaptic GABA(B) receptor activated potassium currents, which
are activated independently on whether the cell fires or not during GDPs; and
(ii) activity-dependent, likely calcium activated potassium currents, whose
contribution to the GDP-AHP is dependent on the amount of firing during GDPs. We
propose that these two complementary inhibitory postsynaptic mechanisms cooperate
in the termination of GDP.
PMID- 28701926
TI - Glutamate Deregulation in Ketamine-Induced Psychosis-A Potential Role of PSD95,
NMDA Receptor and PMCA Interaction.
AB - Ketamine causes psychotic episodes and is often used as pharmacological model of
psychotic-like behavior in animals. There is increasing evidence that molecular
mechanism of its action is more complicated than just N-methyl-D-aspartic acid
(NMDA) receptor antagonism and involves interaction with the components of
calcium homeostatic machinery, in particular plasma membrane calcium pump (PMCA).
Therefore, in this study we aimed to characterize brain region-specific effects
of ketamine on PMCA activity, interaction with NMDA receptor through postsynaptic
density protein 95 (PSD95) scaffolding proteins and glutamate release from nerve
endings. In our study, ketamine induced behavioral changes in healthy male rats
consistent with psychotic effects. In the same animals, we were able to
demonstrate significant inhibition of plasma membrane calcium ATPase (PMCA)
activity in cerebellum, hippocampus and striatum. The expression level and
isoform composition of PMCAs were also affected in some of these brain
compartments, with possible compensatory effects of PMCA1 substituting for
decreased expression of PMCA3. Expression of the PDZ domain-containing scaffold
protein PSD95 was induced and its association with PMCA4 was higher in most brain
compartments upon ketamine treatment. Moreover, increased PSD95/NMDA receptor
direct interaction was also reported, strongly suggesting the formation of
multiprotein complexes potentially mediating the effect of ketamine on calcium
signaling. We further support this molecular mechanism by showing brain region
specific changes in PSD95/PMCA4 spatial colocalization. We also show that
ketamine significantly increases synaptic glutamate release in cortex and
striatum (without affecting total tissue glutamate content), inducing the
expression of vesicular glutamate transporters and decreasing the expression of
membrane glutamate reuptake pump excitatory amino acid transporters 2 (EAAT2).
Thus, ketamine-mediated PMCA inhibition, by decreasing total Ca2+ clearing
potency, may locally raise cytosolic Ca2+ promoting excessive glutamate release.
Regional alterations in glutamate secretion can be further driven by PSD95
mediated spatial recruitment of signaling complexes including glutamate receptors
and calcium pumps, representing a novel mechanism of psychogenic action of
ketamine.
PMID- 28701927
TI - Activation of the CREB/c-Fos Pathway during Long-Term Synaptic Plasticity in the
Cerebellum Granular Layer.
AB - The induction of long-term potentiation and depression (LTP and LTD) is thought
to trigger gene expression and protein synthesis, leading to consolidation of
synaptic and neuronal changes. However, while LTP and LTD have been proposed to
play important roles for sensori-motor learning in the cerebellum granular layer,
their association with these mechanisms remained unclear. Here, we have
investigated phosphorylation of the cAMP-responsive element binding protein
(CREB) and activation of the immediate early gene c-Fos pathway following the
induction of synaptic plasticity by theta-burst stimulation (TBS) in acute
cerebellar slices. LTP and LTD were localized using voltage-sensitive dye imaging
(VSDi). At two time points following TBS (15 min and 120 min), corresponding to
the early and late phases of plasticity, slices were fixed and processed to
evaluate CREB phosphorylation (P-CREB) and c-FOS protein levels, as well as Creb
and c-Fos mRNA expression. High levels of P-CREB and Creb/c-Fos were detected
before those of c-FOS, as expected if CREB phosphorylation triggered gene
expression followed by protein synthesis. No differences between control slices
and slices stimulated with TBS were observed in the presence of an N-methyl-D
aspartate receptor (NMDAR) antagonist. Interestingly, activation of the CREB/c
Fos system showed a relevant degree of colocalization with long-term synaptic
plasticity. These results show that NMDAR-dependent plasticity at the cerebellum
input stage bears about transcriptional and post-transcriptional processes
potentially contributing to cerebellar learning and memory consolidation.
PMID- 28701928
TI - The Hyperpolarization-Activated Current Determines Synaptic Excitability, Calcium
Activity and Specific Viability of Substantia Nigra Dopaminergic Neurons.
AB - Differential vulnerability between Substantia Nigra pars compacta (SNpc) and
Ventral Tegmental Area (VTA) dopaminergic (DAergic) neurons is a hallmark of
Parkinson's disease (PD). Understanding the molecular bases of this key
histopathological aspect would foster the development of much-needed disease
modifying therapies. Non-heterogeneous DAergic degeneration is present in both
toxin-based and genetic animal models, suggesting that cellular specificity,
rather than causing factors, constitutes the background for differential
vulnerability. In this regard, we previously demonstrated that MPP+, a neurotoxin
able to cause selective nigrostriatal degeneration in animal rodents and
primates, inhibits the Hyperpolarization-activated current (Ih) in SNpc DAergic
neurons and that pharmacological Ih antagonism causes potentiation of evoked
Excitatory post-synaptic potentials (EPSPs). Of note, the magnitude of such
potentiation is greater in the SNpc subfield, consistent with higher Ih density.
In the present work, we show that Ih block-induced synaptic potentiation leads to
the amplification of somatic calcium responses (SCRs) in vitro. This effect is
specific for the SNpc subfield and largely mediated by L-Type calcium channels,
as indicated by sensitivity to the CaV 1 blocker isradipine. Furthermore, Ih is
downregulated by low intracellular ATP and determines the efficacy of GABAergic
inhibition in SNpc DAergic neurons. Finally, we show that stereotaxic
administration of Ih blockers causes SNpc-specific neurodegeneration and
hemiparkinsonian motor phenotype in rats. During PD progression, Ih
downregulation may result from mitochondrial dysfunction and, in concert with PD
related disinhibition of excitatory inputs, determine a SNpc-specific disease
pathway.
PMID- 28701929
TI - Anatomic and Physiologic Heterogeneity of Subgroup-A Auditory Sensory Neurons in
Fruit Flies.
AB - The antennal ear of the fruit fly detects acoustic signals in intraspecific
communication, such as the courtship song and agonistic sounds. Among the five
subgroups of mechanosensory neurons in the fly ear, subgroup-A neurons respond
maximally to vibrations over a wide frequency range between 100 and 1,200 Hz. The
functional organization of the neural circuit comprised of subgroup-A neurons,
however, remains largely unknown. In the present study, we used 11 GAL4 strains
that selectively label subgroup-A neurons and explored the diversity of subgroup
A neurons by combining single-cell anatomic analysis and Ca2+ imaging. Our
findings indicate that the subgroup-A neurons that project into various
combinations of subareas in the brain are more anatomically diverse than
previously described. Subgroup-A neurons were also physiologically diverse, and
some types were tuned to a narrow frequency range, suggesting that the response
of subgroup-A neurons to sounds of a wide frequency range is due to the existence
of several types of subgroup-A neurons. Further, we found that an auditory
behavioral response to the courtship song of flies was attenuated when most
subgroup-A neurons were silenced. Together, these findings characterize the
heterogeneous functional organization of subgroup-A neurons, which might
facilitate species-specific acoustic signal detection.
PMID- 28701930
TI - Biogenic Amines in Insect Antennae.
AB - Insect antenna is a multisensory organ, each modality of which can be modulated
by biogenic amines. Octopamine (OA) and its metabolic precursor tyramine (TA)
affect activity of antennal olfactory receptor neurons. There is some evidence
that dopamine (DA) modulates gustatory neurons. Serotonin can serve as a
neurotransmitter in some afferent mechanosensory neurons and both as a
neurotransmitter and neurohormone in efferent fibers targeted at the antennal
vessel and mechanosensory organs. As a neurohormone, serotonin affects the
generation of the transepithelial potential by sensillar accessory cells. Other
possible targets of biogenic amines in insect antennae are hygro- and
thermosensory neurons and epithelial cells. We suggest that the insect antenna is
partially autonomous in the sense that biologically active substances entering
its hemolymph may exert their effects and be cleared from this compartment
without affecting other body parts.
PMID- 28701931
TI - Architecture of the Entorhinal Cortex A Review of Entorhinal Anatomy in Rodents
with Some Comparative Notes.
AB - The entorhinal cortex (EC) is the major input and output structure of the
hippocampal formation, forming the nodal point in cortico-hippocampal circuits.
Different division schemes including two or many more subdivisions have been
proposed, but here we will argue that subdividing EC into two components, the
lateral EC (LEC) and medial EC (MEC) might suffice to describe the functional
architecture of EC. This subdivision then leads to an anatomical interpretation
of the different phenotypes of LEC and MEC. First, we will briefly summarize the
cytoarchitectonic differences and differences in hippocampal projection patterns
on which the subdivision between LEC and MEC traditionally is based and provide a
short comparative perspective. Second, we focus on main differences in cortical
connectivity, leading to the conclusion that the apparent differences may well
correlate with the functional differences. Cortical connectivity of MEC is
features interactions with areas such as the presubiculum, parasubiculum,
retrosplenial cortex (RSC) and postrhinal cortex, all areas that are considered
to belong to the "spatial processing domain" of the cortex. In contrast, LEC is
strongly connected with olfactory areas, insular, medial- and orbitofrontal areas
and perirhinal cortex. These areas are likely more involved in processing of
object information, attention and motivation. Third, we will compare the
intrinsic networks involving principal- and inter-neurons in LEC and MEC.
Together, these observations suggest that the different phenotypes of both EC
subdivisions likely depend on the combination of intrinsic organization and
specific sets of inputs. We further suggest a reappraisal of the notion of EC as
a layered input-output structure for the hippocampal formation.
PMID- 28701932
TI - Functional Connectivity Differences in the Insular Sub-regions in Migraine
without Aura: A Resting-State Functional Magnetic Resonance Imaging Study.
AB - Objective: The objective of this study was to investigate resting-state
functional connectivity (FC) differences in insular sub-regions during the
interictal phase in patients with migraine without aura (MWoA). Methods: Forty
nine MWoA patients (MWoA group) and 48 healthy individuals (healthy control
group) were recruited for this study. All of the subjects underwent neurological
examination and magnetic resonance imaging (MRI). The MRI data were processed
using Brat 1.0 software to obtain a whole-brain FC diagram and using Rest 1.8
software to obtain the FC z-score of the sub-regions of both insulas (six sub
regions on each side). Therefore, there were a total of 12 regions of interest
(ROIs) that were used as seed points for the statistical analysis. Results: There
was abnormal FC between the insular sub-regions and multiple brain regions in the
MWoA patients compared with the healthy control group, and a clear laterality was
also observed. In addition, the FC z-score of certain sub-regions was negatively
correlated with the disease duration. Conclusion: Different insular sub-regions
are functionally associated with different regions of the brain and therefore
have different functions. In MWoA, the FC between the insular sub-regions and
other brain regions was mostly reduced, while a small amount was increased;
additionally, the FC may be ipsilateral with a right-side advantage. Variations
in the FC of insular sub-regions can be observed as an important indicator of
MWoA.
PMID- 28701933
TI - Network Efficiency and Posterior Alpha Patterns Are Markers of Recovery from
General Anesthesia: A High-Density Electroencephalography Study in Healthy
Volunteers.
AB - Recent studies have investigated local oscillations, long-range connectivity, and
global network patterns to identify neural changes associated with anesthetic
induced unconsciousness. These studies typically employ anesthetic protocols that
either just cross the threshold of unconsciousness, or induce deep
unconsciousness for a brief period of time-neither of which models general
anesthesia for major surgery. To study neural patterns of unconsciousness and
recovery in a clinically-relevant context, we used a realistic anesthetic regimen
to induce and maintain unconsciousness in eight healthy participants for 3 h.
High-density electroencephalogram (EEG) was acquired throughout and for another 3
h after emergence. Seven epochs of 5-min eyes-closed resting states were
extracted from the data at baseline as well as 30, 60, 90, 120, 150, and 180-min
post-emergence. Additionally, 5-min epochs were extracted during induction,
unconsciousness, and immediately prior to recovery of consciousness, for a total
of 10 analysis epochs. The EEG data in each epoch were analyzed using source
localized spectral analysis, phase-lag index, and graph theoretical techniques.
Posterior alpha power was significantly depressed during unconsciousness, and
gradually approached baseline levels over the 3 h recovery period. Phase-lag
index did not distinguish between states of consciousness or stages of recovery.
Network efficiency was significantly depressed and network clustering coefficient
was significantly increased during unconsciousness; these graph theoretical
measures returned to baseline during the 3 h recovery period. Posterior alpha
power may be a potential biomarker for normal recovery of functional brain
networks after general anesthesia.
PMID- 28701934
TI - Neuronal Intra-Individual Variability Masks Response Selection Differences
between ADHD Subtypes-A Need to Change Perspectives.
AB - Due to the high intra-individual variability in attention deficit/hyperactivity
disorder (ADHD), there may be considerable bias in knowledge about altered
neurophysiological processes underlying executive dysfunctions in patients with
different ADHD subtypes. When aiming to establish dimensional cognitive
neurophysiological constructs representing symptoms of ADHD as suggested by the
initiative for Research Domain Criteria, it is crucial to consider such processes
independent of variability. We examined patients with the predominantly
inattentive subtype (attention deficit disorder, ADD) and the combined subtype of
ADHD (ADHD-C) in a flanker task measuring conflict control. Groups were matched
for task performance. Besides using classic event-related potential (ERP)
techniques and source localization, neurophysiological data was also analyzed
using residue iteration decomposition (RIDE) to statistically account for intra
individual variability and S-LORETA to estimate the sources of the activations.
The analysis of classic ERPs related to conflict monitoring revealed no
differences between patients with ADD and ADHD-C. When individual variability was
accounted for, clear differences became apparent in the RIDE C-cluster (analog to
the P3 ERP-component). While patients with ADD distinguished between compatible
and incompatible flanker trials early on, patients with ADHD-C seemed to employ
more cognitive resources overall. These differences are reflected in inferior
parietal areas. The study demonstrates differences in neuronal mechanisms related
to response selection processes between ADD and ADHD-C which, according to source
localization, arise from the inferior parietal cortex. Importantly, these
differences could only be detected when accounting for intra-individual
variability. The results imply that it is very likely that differences in
neurophysiological processes between ADHD subtypes are underestimated and have
not been recognized because intra-individual variability in neurophysiological
data has not sufficiently been taken into account.
PMID- 28701935
TI - Cardiorespiratory Fitness Is Associated with Selective Attention in Healthy Male
High-School Students.
AB - Background: Previous studies have shown associations of physical fitness and
cognition in children and in younger and older adults. However, knowledge about
associations in high-school adolescents and young adults is sparse. Thus, the aim
of this study was to evaluate the association of physical fitness, measured as
maximal oxygen uptake ([Formula: see text]), muscle mass, weekly training, and
cognitive function in the executive domains of selective attention and inhibitory
control, in healthy male high-school students. Methods: Fifty-four males (17.9 +/
0.9 years, 72 +/- 11 kg and 182 +/- 7 cm) completed a [Formula: see text] test,
a body composition test and a visual cognitive task based on the Posner cue
paradigm with three types of stimuli with different attentional demands (i.e.,
stimuli presentation following no cue, valid cue or invalid cue presentations).
The task consisted of 336 target stimuli, where 56 (17%) of the target stimuli
appeared without a cue (no cue), 224 (67%) appeared in the same rectangle as the
cue (valid cue) and 56 (17%) appeared in the rectangle opposite to the cue
(invalid cue). Mean reaction time (RT) and corresponding errors was calculated
for each stimuli type. Total task duration was 9 min and 20 s In addition,
relevant background information was obtained in a questionnaire. Results: Linear
mixed model analyses showed that higher [Formula: see text] was associated with
faster RT for stimuli following invalid cue (Estimate = -2.69, SE = 1.03, p =
0.011), and for stimuli following valid cue (Estimate = -2.08, SE = 1.03, p =
0.048). There was no association of muscle mass and stimuli (F = 1.01, p = 0.397)
or of weekly training and stimuli (F = 0.99, p = 0.405). Conclusion: The results
suggest that cardiorespiratory fitness is associated with cognitive performance
in healthy male high-school students in the executive domains of selective
attention.
PMID- 28701936
TI - An Adaptation-Induced Repulsion Illusion in Tactile Spatial Perception.
AB - Following focal sensory adaptation, the perceived separation between visual
stimuli that straddle the adapted region is often exaggerated. For instance, in
the tilt aftereffect illusion, adaptation to tilted lines causes subsequently
viewed lines with nearby orientations to be perceptually repelled from the
adapted orientation. Repulsion illusions in the nonvisual senses have been less
studied. Here, we investigated whether adaptation induces a repulsion illusion in
tactile spatial perception. In a two-interval forced-choice task, participants
compared the perceived separation between two point-stimuli applied on the
forearms successively. Separation distance was constant on one arm (the
reference) and varied on the other arm (the comparison). In Experiment 1, we took
three consecutive baseline measurements, verifying that in the absence of
manipulation, participants' distance perception was unbiased across arms and
stable across experimental blocks. In Experiment 2, we vibrated a region of skin
on the reference arm, verifying that this focally reduced tactile sensitivity, as
indicated by elevated monofilament detection thresholds. In Experiment 3, we
applied vibration between the two reference points in our distance perception
protocol and discovered that this caused an illusory increase in the separation
between the points. We conclude that focal adaptation induces a repulsion
aftereffect illusion in tactile spatial perception. The illusion provides clues
as to how the tactile system represents spatial information. The analogous
repulsion aftereffects caused by adaptation in different stimulus domains and
sensory systems may point to fundamentally similar strategies for dynamic sensory
coding.
PMID- 28701937
TI - Neuroplasticity and Functional Recovery after Intensive Language Therapy in
Chronic Post Stroke Aphasia: Which Factors Are Relevant?
PMID- 28701938
TI - Improving EEG-Based Emotion Classification Using Conditional Transfer Learning.
AB - To overcome the individual differences, an accurate electroencephalogram (EEG)
based emotion-classification system requires a considerable amount of ecological
calibration data for each individual, which is labor-intensive and time
consuming. Transfer learning (TL) has drawn increasing attention in the field of
EEG signal mining in recent years. The TL leverages existing data collected from
other people to build a model for a new individual with little calibration data.
However, brute-force transfer to an individual (i.e., blindly leveraged the
labeled data from others) may lead to a negative transfer that degrades
performance rather than improving it. This study thus proposed a conditional TL
(cTL) framework to facilitate a positive transfer (improving subject-specific
performance without increasing the labeled data) for each individual. The cTL
first assesses an individual's transferability for positive transfer and then
selectively leverages the data from others with comparable feature spaces. The
empirical results showed that among 26 individuals, the proposed cTL framework
identified 16 and 14 transferable individuals who could benefit from the data
from others for emotion valence and arousal classification, respectively. These
transferable individuals could then leverage the data from 18 and 12 individuals
who had similar EEG signatures to attain maximal TL improvements in valence- and
arousal-classification accuracy. The cTL improved the overall classification
performance of 26 individuals by ~15% for valence categorization and ~12% for
arousal counterpart, as compared to their default performance based solely on the
subject-specific data. This study evidently demonstrated the feasibility of the
proposed cTL framework for improving an individual's default emotion
classification performance given a data repository. The cTL framework may shed
light on the development of a robust emotion-classification model using fewer
labeled subject-specific data toward a real-life affective brain-computer
interface (ABCI).
PMID- 28701939
TI - Behavioral and Cortical Effects during Attention Driven Brain-Computer Interface
Operations in Spatial Neglect: A Feasibility Case Study.
AB - During the last years, several studies have suggested that Brain-Computer
Interface (BCI) can play a critical role in the field of motor rehabilitation. In
this case report, we aim to investigate the feasibility of a covert visuospatial
attention (CVSA) driven BCI in three patients with left spatial neglect (SN). We
hypothesize that such a BCI is able to detect attention task-specific brain
patterns in SN patients and can induce significant changes in their abnormal
cortical activity (alpha-power modulation, feature recruitment, and
connectivity). The three patients were asked to control online a CVSA BCI by
focusing their attention at different spatial locations, including their
neglected (left) space. As primary outcome, results show a significant
improvement of the reaction time in the neglected space between calibration and
online modalities (p < 0.01) for the two out of three patients that had the
slowest initial behavioral response. Such an evolution of reaction time
negatively correlates (p < 0.05) with an increment of the Individual alpha-Power
computed in the pre-cue interval. Furthermore, all patients exhibited a
significant reduction of the inter-hemispheric imbalance (p < 0.05) over time in
the parieto-occipital regions. Finally, analysis on the inter-hemispheric
functional connectivity suggests an increment across modalities for regions in
the affected (right) hemisphere and decrement for those in the healthy. Although
preliminary, this feasibility study suggests a possible role of BCI in the
therapeutic treatment of lateralized, attention-based visuospatial deficits.
PMID- 28701940
TI - Reduced Pain Sensation and Reduced BOLD Signal in Parietofrontal Networks during
Religious Prayer.
AB - Previous studies suggest that religious prayer can alter the experience of pain
via expectation mechanisms. While brain processes related to other types of top
down modulation of pain have been studied extensively, no research has been
conducted on the potential effects of active religious coping. Here, we aimed at
investigating the neural mechanisms during pain modulation by prayer and their
dependency on the opioidergic system. Twenty-eight devout Protestants performed
religious prayer and a secular contrast prayer during painful electrical
stimulation in two fMRI sessions. Naloxone or saline was administered prior to
scanning. Results show that pain intensity was reduced by 11% and pain
unpleasantness by 26% during religious prayer compared to secular prayer.
Expectancy predicted large amounts (70-89%) of the variance in pain intensity.
Neuroimaging results revealed reduced neural activity during religious prayer in
a large parietofrontal network relative to the secular condition. Naloxone had no
significant effect on ratings or neural activity. Our results thus indicate that,
under these conditions, pain modulation by prayer is not opioid-dependent.
Further studies should employ an optimized design to explore whether reduced
engagement of the frontoparietal system could indicate that prayer may attenuate
pain through a reduction in processing of pain stimulus saliency and prefrontal
control rather than through known descending pain inhibitory systems.
PMID- 28701941
TI - Rapid Alleviation of Parkinson's Disease Symptoms via Electrostimulation of
Intrinsic Auricular Muscle Zones.
AB - Background: Deep brain stimulation of the subthalamic nucleus (STN-DBS) and the
pedunculopontine nucleus (PPN) significantly improve cardinal motor symptoms and
postural instability and gait difficulty, respectively, in Parkinson's disease
(PD). Objective and Hypothesis: Intrinsic auricular muscle zones (IAMZs) allow
the potential to simultaneously stimulate the C2 spinal nerve, the trigeminal
nerve, the facial nerve, and sympathetic and parasympathetic nerves in addition
to providing muscle feedback and control areas including the STN, the PPN and
mesencephalic locomotor regions. Our aim was to observe the clinical responses to
IAMZ stimulation in PD patients. Method: Unilateral stimulation of an IAMZ, which
includes muscle fibers for proprioception, the facial nerve, and C2, trigeminal
and autonomic nerve fibers, at 130 Hz was performed in a placebo- and sham
controlled, double-blinded, within design, two-armed study of 24 PD patients.
Results: The results of the first arm (10 patients) of the present study
demonstrated a substantial improvement in Unified Parkinson's Disease Ratings
Scale (UPDRS) motor scores due to 10 min of IAMZ electrostimulation (p = 0.0003,
power: 0.99) compared to the placebo control (p = 0.130). A moderate to large
clinical difference in the improvement in UPDRS motor scores was observed in the
IAMZ electrostimulation group. The results of the second arm (14 patients)
demonstrated significant improvements with dry needling (p = 0.011) and
electrostimulation of the IAMZ (p < 0.001) but not with sham electrostimulation
(p = 0.748). In addition, there was a significantly greater improvement in UPDRS
motor scores in the IAMZ electrostimulation group compared to the IAMZ dry
needling group (p < 0.001) and the sham electrostimulation (p < 0.001) groups.
The improvement in UPDRS motor scores of the IAMZ electrostimulation group
(DeltaUPDRS = 5.29) reached moderate to high clinical significance, which was not
the case for the dry needling group (DeltaUPDRS = 1.54). In addition, both arms
of the study demonstrated bilateral improvements in motor symptoms in response to
unilateral IAMZ electrostimulation. Conclusion: The present study is the first
demonstration of a potential role of IAMZ electrical stimulation in improving the
clinical motor symptoms of PD patients in the short term.
PMID- 28701942
TI - Neural Mechanisms Underlying Conscious and Unconscious Gaze-Triggered Attentional
Orienting in Autism Spectrum Disorder.
AB - Impaired joint attention represents the core clinical feature of autism spectrum
disorder (ASD). Behavioral studies have suggested that gaze-triggered attentional
orienting is intact in response to supraliminally presented eyes but impaired in
response to subliminally presented eyes in individuals with ASD. However, the
neural mechanisms underlying conscious and unconscious gaze-triggered attentional
orienting remain unclear. We investigated this issue in ASD and typically
developing (TD) individuals using event-related functional magnetic resonance
imaging. The participants viewed cue stimuli of averted or straight eye gaze
direction presented either supraliminally or subliminally and then localized a
target. Reaction times were shorter when eye-gaze cues were directionally valid
compared with when they were neutral under the supraliminal condition in both
groups; the same pattern was found in the TD group but not the ASD group under
the subliminal condition. The temporo-parieto-frontal regions showed stronger
activation in response to averted eyes than to straight eyes in both groups under
the supraliminal condition. The left amygdala was more activated while viewing
averted vs. straight eyes in the TD group than in the ASD group under the
subliminal condition. These findings provide an explanation for the neural
mechanisms underlying the impairment in unconscious but not conscious gaze
triggered attentional orienting in individuals with ASD and suggest possible
neurological and behavioral interventions to facilitate their joint attention
behaviors.
PMID- 28701943
TI - Aberrant Long-Range Temporal Correlations in Depression Are Attenuated after
Psychological Treatment.
AB - The spontaneous oscillatory activity in the human brain shows long-range temporal
correlations (LRTC) that extend over time scales of seconds to minutes. Previous
research has demonstrated aberrant LRTC in depressed patients; however, it is
unknown whether the neuronal dynamics normalize after psychological treatment. In
this study, we recorded EEG during eyes-closed rest in depressed patients (N =
71) and healthy controls (N = 25), and investigated the temporal dynamics in
depressed patients at baseline, and after attending either a brief mindfulness
training or a stress reduction training. Compared to the healthy controls,
depressed patients showed stronger LRTC in theta oscillations (4-7 Hz) at
baseline. Following the psychological interventions both groups of patients
demonstrated reduced LRTC in the theta band. The reduction of theta LRTC differed
marginally between the groups, and explorative analyses of separate groups
revealed noteworthy topographic differences. A positive relationship between the
changes in LRTC, and changes in depressive symptoms was observed in the
mindfulness group. In summary, our data show that aberrant temporal dynamics of
ongoing oscillations in depressive patients are attenuated after treatment, and
thus may help uncover the mechanisms with which psychotherapeutic interventions
affect the brain.
PMID- 28701944
TI - Commentary: Cluster failure: Why fMRI inferences for spatial extent have inflated
false-positive rates.
PMID- 28701945
TI - Magnetoencephalography in Preoperative Epileptic Foci Localization: Enlightenment
from Cognitive Studies.
AB - Over 30% epileptic patients are refractory to medication, who are amenable to
neurosurgical treatment. Non-invasive brain imaging technologies including video
electroencephalogram (EEG), magnetic resonance imaging (MRI), and
magnetoencephalography (MEG) are widely used in presurgical assessment of
epileptic patients. This review mainly discussed the current development of
clinical MEG imaging as a diagnose approach, and its correlations with the golden
standard intracranial electroencephalogram (iEEG). More importantly, this review
discussed the possible applications of functional networks in preoperative
epileptic foci localization in future studies.
PMID- 28701946
TI - The NEST Dry-Run Mode: Efficient Dynamic Analysis of Neuronal Network Simulation
Code.
AB - NEST is a simulator for spiking neuronal networks that commits to a general
purpose approach: It allows for high flexibility in the design of network models,
and its applications range from small-scale simulations on laptops to brain-scale
simulations on supercomputers. Hence, developers need to test their code for
various use cases and ensure that changes to code do not impair scalability.
However, running a full set of benchmarks on a supercomputer takes up precious
compute-time resources and can entail long queuing times. Here, we present the
NEST dry-run mode, which enables comprehensive dynamic code analysis without
requiring access to high-performance computing facilities. A dry-run simulation
is carried out by a single process, which performs all simulation steps except
communication as if it was part of a parallel environment with many processes. We
show that measurements of memory usage and runtime of neuronal network
simulations closely match the corresponding dry-run data. Furthermore, we
demonstrate the successful application of the dry-run mode in the areas of
profiling and performance modeling.
PMID- 28701947
TI - Protein-Restricted Diets for Ameliorating Motor Fluctuations in Parkinson's
Disease.
AB - Levodopa is considered to be the most effective symptomatic drug for Parkinson's
disease (PD). As the disease progresses, however, the patients are likely to
experience a reduced response to levodopa and develop motor fluctuations (i.e.,
end-of-dose wearing off and unpredictable "on-off"). Protein-rich diets and
elevated plasma concentrations of large neutral amino acids have been proved to
impair the therapeutic effect of levodopa by reducing its absorption and influx
into the brain. On the other hand, the protein-restricted diets including low
protein diet (LPD), protein-redistribution diet (PRD) and PRD with use of low
protein products can all improve the efficacy of levodopa in patients with motor
fluctuations. However, it should be noted that protein-restricted diets may also
contribute to several side effects, including dyskinesia, weight loss, and
malnutrition (e.g., protein and calcium insufficiency). Together, protein
restricted diets are an effective approach to improve motor fluctuations in PD
patients, while long-term adherence to these diets requires monitoring for side
effects.
PMID- 28701949
TI - Editorial: The Metabolic-Inflammatory Axis in Brain Aging and Neurodegeneration.
PMID- 28701948
TI - Microglial Activation in Traumatic Brain Injury.
AB - Microglia have a variety of functions in the brain, including synaptic pruning,
CNS repair and mediating the immune response against peripheral infection.
Microglia rapidly become activated in response to CNS damage. Depending on the
nature of the stimulus, microglia can take a number of activation states, which
correspond to altered microglia morphology, gene expression and function. It has
been reported that early microglia activation following traumatic brain injury
(TBI) may contribute to the restoration of homeostasis in the brain. On the other
hand, if they remain chronically activated, such cells display a classically
activated phenotype, releasing pro-inflammatory molecules, resulting in further
tissue damage and contributing potentially to neurodegeneration. However, new
evidence suggests that this classification is over-simplistic and the balance of
activation states can vary at different points. In this article, we review the
role of microglia in TBI, analyzing their distribution, morphology and functional
phenotype over time in animal models and in humans. Animal studies have allowed
genetic and pharmacological manipulations of microglia activation, in order to
define their role. In addition, we describe investigations on the in vivo imaging
of microglia using translocator protein (TSPO) PET and autoradiography, showing
that microglial activation can occur in regions far remote from sites of focal
injuries, in humans and animal models of TBI. Finally, we outline some novel
potential therapeutic approaches that prime microglia/macrophages toward the
beneficial restorative microglial phenotype after TBI.
PMID- 28701950
TI - Cerebrospinal Fluid Abeta43 Is Reduced in Early-Onset Compared to Late-Onset
Alzheimer's Disease, But Has Similar Diagnostic Accuracy to Abeta42.
AB - : Background: Amyloid beta 1-43 (Abeta43) may be a useful additional biomarker
for diagnosing Alzheimer's disease (AD). We have investigated cerebrospinal fluid
(CSF) levels of Abeta43 in patients with early-onset AD in contrast to levels in
late-onset AD. For comparison, in addition to the 'core' biomarkers, several
other analytes were also determined [YKL-40, neurofilament light (NF-L), glial
fibrillary acidic protein (GFAP), and progranulin]. Material and Methods:
Cerebrospinal fluid samples were obtained from patients with early-onset AD (age
<= 62, n = 66), late-onset AD (age >= 68, n = 25), and groups of cognitively
intact individuals (age <= 62, n = 41, age >= 68, n = 39). Core CSF AD biomarkers
[amyloid beta 1-42 (Abeta42), total tau, phosphorylated tau] were analyzed, as
well as levels of Abeta43 and other analytes, using commercially available enzyme
linked immunosorbent assays. Results: Cerebrospinal fluid Abeta43 was
significantly reduced in early-onset AD compared to late-onset AD (14.8 +/- 7.3
vs. 21.8 +/- 9.4 pg/ml, respectively), whereas the levels of Abeta42 in the two
AD groups were not significantly different (474.9 +/- 142.0 vs. 539.6 +/- 159.9
pg/ml, respectively). Abeta43 and all core biomarkers were significantly altered
in patients with AD compared to corresponding controls. NF-L was significantly
increased in early-onset AD compared to younger controls, an effect not found
between the older groups. Relationships between the Abeta peptides and tau
proteins, YKL-40, NF-L, GFAP and progranulin were also investigated without
finding marked associations. However, age-associated increases in levels of tau
proteins, YKL-40, NF-L and GFAP were found with respect to age in healthy
controls. Results for these other analytes were similar to previously published
data. Abeta43 did not improve diagnostic accuracy in either AD group compared to
Abeta42. DISCUSSION: Cerebrospinal fluid Abeta43, but not Abeta42 levels, varied
significantly with age in patients with AD. If CSF levels of Abeta peptides
reflect amyloid deposition in brain, the possibility arises that there is a
difference between Abeta43 and Abeta42 deposition in younger compared to older
brain. However, the level of Abeta43 in CSF shows no improvement over Abeta42
regarding diagnostic accuracy.
PMID- 28701951
TI - Pharmacokinetic/Pharmacodynamic Modeling of Tulathromycin against Pasteurella
multocida in a Porcine Tissue Cage Model.
AB - Tulathromycin, a macrolide antibiotic, is used for the treatment of respiratory
disease in cattle and swine. The aim of our study was to investigate the in vitro
and ex vivo activities of tulathromycin in serum, (non-inflamed) transudate, and
(inflamed) exudate against Pasteurella multocida in piglets. The pharmacokinetics
properties of tulathromycin were studied for serum, transudate, and exudate using
a tissue cage model. In vitro antibiotic susceptibility of P. multocida and
dynamic time-kill curve experiments over eight tulathromycin concentrations were
determined. The ratio of 24-h area under the concentration-time curve to minimum
inhibitory concentration [AUC(0-24 h)/MIC] was recognized as an important
pharmacokinetic/pharmacodynamic (PK/PD) parameter of tulathromycin for
antibacterial efficiency (R2 = 0.9969). In serum ex vivo, for bacteriostatic,
bactericidal activity, and virtual bacterial eradication AUC(0-24 h)/MIC values
for tulathromycin were 44.55, 73.19, and 92.44 h by using sigmoid Emax model
WinNonlin software, respectively, and lower values were obtained for exudate and
transudate. In conjunction with the data on MIC90, the dose of tulathromycin for
a bacteriostatic effect and virtual elimination of P. multocida as computed using
the value of the PK/PD breakpoint obtained in serum were 6.39 and 13.25 mg/kg.
However, it would be preferable to calculate a dose combined with population
pharmacokinetics data to optimize the dosage regimen for bacteriological and
clinical cure.
PMID- 28701952
TI - A Systematic Review of the Immune-Regulating and Anticancer Activities of
Pseudolaric Acid B.
AB - Cortex pseudolaricis, the root bark of Pseudolarix kaempferi Gord, has been used
to treat tinea and other skin diseases for the antimicrobial activities in
Traditional Chinese Medicine (TCM). Pseudolaric acid B (PAB) has been identified
as the major component responsible for the action of C. pseudolaricis. Recently,
PAB has been demonstrated to be used as novel treatments for cancer, immune
disorders, inflammatory diseases, and immunosuppression. However, the mechanisms
through which PAB exerts its properties are not understood well, and little
attention in the literature has been given to review its pharmacological
activities before. In this review, we performed a systematic summary of the
literature with respect to the anticancer, immunosuppressive and anti
inflammatory properties of PAB and its derivatives. Currently available data
suggest that PAB is a promising immunosuppressive and anti-inflammatory agent
candidate and should be explored further in cancer treatment and prevention.
PMID- 28701953
TI - Astrocyte Activation in Locus Coeruleus Is Involved in Neuropathic Pain
Exacerbation Mediated by Maternal Separation and Social Isolation Stress.
AB - Our previous studies demonstrated that emotional dysfunction associated with
early life stress exacerbated nerve injury-induced mechanical allodynia. Sex
differences were observed in several anxiety tests, but not in mechanical
allodynia. To elucidate the mechanism underlying these findings, we have now
investigated the involvement of astrocytes in emotional dysfunction and
enhancement of nerve injury-induced mechanical allodynia in mice subjected to
maternal separation combined with social isolation (MSSI) as an early life
stress. We measured expression of glial fibrillary acidic protein (GFAP), an
astrocyte maker, in each brain area by immunohistochemistry. GFAP expression in
the locus coeruleus (LC) of female, but not of male mice, significantly increased
after MSSI, corresponding to the behavioral changes at 7 and 12 weeks of age.
Lipopolysaccharide (LPS)-treated astrocyte-derived supernatant was administered
to local brain regions, including LC. Intra-LC injection of conditioned medium
from cultured astrocytes treated with LPS increased GFAP expression, anxiety-like
behavior and mechanical allodynia in both male and female mice. Furthermore,
increases in anxiety-like behavior correlated with increased mechanical
allodynia. These findings demonstrate that emotional dysfunction and enhanced
nerve injury-induced mechanical allodynia after exposure to MSSI are mediated, at
least in part, by astrocyte activation in the LC. Male but not female mice may
show resistance to MSSI stress during growth.
PMID- 28701954
TI - Shexiang Baoxin Pills for Coronary Heart Disease in Animal Models: Preclinical
Evidence and Promoting Angiogenesis Mechanism.
AB - Shexiang Baoxin Pill (SBP) originated from a classical TCM Fufang Suhexiang Pill
for chest pain with dyspnea in the Southern Song Dynasty (1107-110 AD). Here, we
aimed to evaluate preclinical evidence and possible mechanism of SBP for
experimental coronary heart disease (CHD). Studies of SBP in animal models with
CHD were identified from 6 databases until April 2016. Study quality for each
included article was evaluated according to the CAMARADES 10-item checklist.
Outcome measures were myocardial infarction area, vascular endothelial growth
factor (VEGF) and microvessel count (MVC). All the data were analyzed by using
RevMan 5.1 software. As a consequence, 25 studies with 439 animals were
identified. The quality score of studies ranged from 2 to 5, with the median of
3.6. Meta-analysis of seven studies showed more significant effects of SBP on the
reduction of the myocardial infarction area than the control (P < 0.01). Meta
analysis of eight studies showed significant effects of SBP for increasing VEGF
expression compared with the control (P < 0.01). Meta-analysis of 10 studies
indicated that SBP significantly improved MVC compared with the control (P <
0.01). In conclusion, these findings preliminarily demonstrated that SBP can
reduce myocardial infarction area, exerting cardioprotective function largely
through promoting angiogenesis.
PMID- 28701955
TI - Therapeutic Properties of Bioactive Compounds from Different Honeybee Products.
AB - Honeybees produce honey, royal jelly, propolis, bee venom, bee pollen, and
beeswax, which potentially benefit to humans due to the bioactives in them.
Clinical standardization of these products is hindered by chemical variability
depending on honeybee and botanical sources, but different molecules have been
isolated and pharmacologically characterized. Major honey bioactives include
phenolics, methylglyoxal, royal jelly proteins (MRJPs), and oligosaccharides. In
royal jelly there are antimicrobial jelleins and royalisin peptides, MRJPs, and
hydroxy-decenoic acid derivatives, notably 10-hydroxy-2-decenoic acid (10-HDA),
with antimicrobial, anti-inflammatory, immunomodulatory, neuromodulatory,
metabolic syndrome preventing, and anti-aging activities. Propolis contains
caffeic acid phenethyl ester and artepillin C, specific of Brazilian propolis,
with antiviral, immunomodulatory, anti-inflammatory and anticancer effects. Bee
venom consists of toxic peptides like pain-inducing melittin, SK channel blocking
apamin, and allergenic phospholipase A2. Bee pollen is vitaminic, contains
antioxidant and anti-inflammatory plant phenolics, as well as
antiatherosclerotic, antidiabetic, and hypoglycemic flavonoids, unsaturated fatty
acids, and sterols. Beeswax is widely used in cosmetics and makeup. Given the
importance of drug discovery from natural sources, this review is aimed at
providing an exhaustive screening of the bioactive compounds detected in honeybee
products and of their curative or adverse biological effects.
PMID- 28701956
TI - Administration of a Histone Deacetylase Inhibitor into the Basolateral Amygdala
Enhances Memory Consolidation, Delays Extinction, and Increases Hippocampal BDNF
Levels.
AB - Gene expression related to the formation and modification of memories is
regulated epigenetically by chromatin remodeling through histone acetylation.
Memory formation and extinction can be enhanced by treatment with inhibitors of
histone deacetylases (HDACs). The basolateral amygdala (BLA) is a brain area
critically involved in regulating memory for inhibitory avoidance (IA). However,
previous studies have not examined the effects of HDAC inhibition in the amygdala
on memory for IA. Here we show that infusion of an HDAC inhibitor (HDACi),
trichostatin A (TSA), into the BLA, enhanced consolidation of IA memory in rats
when given at 1.5, 3, or 6 h posttraining, but not when the drug was infused
immediately after training. In addition, intra-BLA administration of TSA
immediately after retrieval delayed extinction learning. Moreover, we show that
intra-BLA TSA in rats given IA training increased the levels of brain-derived
neurotrophic factor in the dorsal hippocampus, but not in the BLA itself. These
findings reveal novel aspects of the regulation of fear memory by epigenetic
mechanisms in the amygdala.
PMID- 28701957
TI - An Overview on Medicinal Chemistry of Synthetic and Natural Derivatives of
Cannabidiol.
AB - Cannabidiol (CBD) has been traditionally used in Cannabis-based preparation,
however historically, it has received far less interest as a single drug than the
other components of Cannabis. Currently, CBD generates considerable interest due
to its beneficial neuroprotective, antiepileptic, anxiolytic, antipsychotic, and
anti-inflammatory properties. Therefore, the CBD scaffold becomes of increasing
interest for medicinal chemists. This review provides an overview of the chemical
structure of natural and synthetic CBD derivatives including the molecular
targets associated with these compounds. A clear identification of their
biological targets has been shown to be still very challenging.
PMID- 28701958
TI - A Single Dose of LSD Does Not Alter Gene Expression of the Serotonin 2A Receptor
Gene (HTR2A) or Early Growth Response Genes (EGR1-3) in Healthy Subjects.
AB - Rationale: Renewed interest has been seen in the use of lysergic acid
diethylamide (LSD) in psychiatric research and practice. The repeated use of LSD
leads to tolerance that is believed to result from serotonin (5-HT) 5-HT2A
receptor downregulation. In rats, daily LSD administration for 4 days decreased
frontal cortex 5-HT2A receptor binding. Additionally, a single dose of LSD
acutely increased expression of the early growth response genes EGR1 and EGR2 in
rat and mouse brains through 5-HT2A receptor stimulation. No human data on the
effects of LSD on gene expression has been reported. Therefore, we investigated
the effects of single-dose LSD administration on the expression of the 5-HT2A
receptor gene (HTR2A) and EGR1-3 genes. Methods: mRNA expression levels were
analyzed in whole blood as a peripheral biomarker in 15 healthy subjects before
and 1.5 and 24 h after the administration of LSD (100 MUg) and placebo in a
randomized, double-blind, placebo-controlled, cross-over study. Results: LSD did
not alter the expression of the HTR2A or EGR1-3 genes 1.5 and 24 h after
administration compared with placebo. Conclusion: No changes were observed in the
gene expression of LSD's primary target receptor gene or genes that are
implicated in its downstream effects. Remaining unclear is whether chronic LSD
administration alters gene expression in humans.
PMID- 28701959
TI - Renal Oxygenation in the Pathophysiology of Chronic Kidney Disease.
AB - Chronic kidney disease (CKD) is a significant health problem associated with high
morbidity and mortality. Despite significant research into various pathways
involved in the pathophysiology of CKD, the therapeutic options are limited in
diabetes and hypertension induced CKD to blood pressure control, hyperglycemia
management (in diabetic nephropathy) and reduction of proteinuria, mainly with
renin-angiotensin blockade therapy. Recently, renal oxygenation in
pathophysiology of CKD progression has received a lot of interest. Several
advances have been made in our understanding of the determinants and regulators
of renal oxygenation in normal and diseased kidneys. The goal of this review is
to discuss the alterations in renal oxygenation (delivery, consumption and tissue
oxygen tension) in pre-clinical and clinical studies in diabetic and hypertensive
CKD along with the underlying mechanisms and potential therapeutic options.
PMID- 28701960
TI - Role of Mitochondrial Reverse Electron Transport in ROS Signaling: Potential
Roles in Health and Disease.
AB - Reactive Oxygen Species (ROS) can cause oxidative damage and have been proposed
to be the main cause of aging and age-related diseases including cancer, diabetes
and Parkinson's disease. Accordingly, mitochondria from old individuals have
higher levels of ROS. However, ROS also participate in cellular signaling, are
instrumental for several physiological processes and boosting ROS levels in model
organisms extends lifespan. The current consensus is that low levels of ROS are
beneficial, facilitating adaptation to stress via signaling, whereas high levels
of ROS are deleterious because they trigger oxidative stress. Based on this model
the amount of ROS should determine the physiological effect. However, recent data
suggests that the site at which ROS are generated is also instrumental in
determining effects on cellular homeostasis. The best example of site-specific
ROS signaling is reverse electron transport (RET). RET is produced when electrons
from ubiquinol are transferred back to respiratory complex I, reducing NAD+ to
NADH. This process generates a significant amount of ROS. RET has been shown to
be instrumental for the activation of macrophages in response to bacterial
infection, re-organization of the electron transport chain in response to changes
in energy supply and adaptation of the carotid body to changes in oxygen levels.
In Drosophila melanogaster, stimulating RET extends lifespan. Here, we review
what is known about RET, as an example of site-specific ROS signaling, and its
implications for the field of redox biology.
PMID- 28701962
TI - The Effect of Calendula officinalis on Oxidative Stress and Bone Loss in
Experimental Periodontitis.
AB - Periodontitis is associated with reduced antioxidant capacity and increased
oxidative damage. Oxidative stress induces inflammation and bone loss
contributing to the pathological progression of periodontal disease. Calendula
officinalis (CLO) has demonstrated anti-inflammatory and anti-oxidant activities.
Therefore, the aim of this study was to evaluate the effect of CLO on oxidative
stress and bone loss in rats subjected to experimental periodontitis (EP). For
this, 72 male Wistar rats were divided into groups: Naive, Saline (SAL) and CLO.
Rats received SAL or CLO (90 mg/kg) 30 min before ligature and daily until the
11th day. Naive group experienced no manipulation. After 11 days, the animals
were euthanized and left maxillae collected for macroscopic analysis of alveolar
bone loss (ABL). Periodontium was analyzed by macroscopy, scanning electron
microscopy; confocal and light polarized microscopy. Immunohistochemical
examination of DKK1, WNT 10b and beta-catenin was performed. The gingival tissue
was collected to reduced glutathione (GSH), superoxide dismutase (SOD), catalase
(CAT) and malondialdehyde (MDA) analyses. The 11 days of ligature induced bone
loss, breakdown of collagen fibers, increased the immunostaining DKK-1 while
reduced WNT 10b and beta-catenin expressions. Periodontitis reduced GSH, SOD, CAT
and increase MDA. All findings were reversed by 90 mg/kg of CLO. In summary our
findings demonstrated that CLO reduced oxidative stress and bone loss and
preserved collagen fibers in rats with EP, with participation of WNT signaling
pathway.
PMID- 28701963
TI - Hoarding Disorder: A Case Report.
AB - Hoarding disorder is characterized by a persistent difficulty discarding items,
the desire to save items to avoid negative feelings associated with discarding
them, significant accumulation of possessions that clutter active living areas
and significant distress or impairment in areas of functioning. We present a case
of a 52-year-old married man who was referred to the psychiatry department for
collecting various objects that were deposited unorganized in the patient's
house. He reported to get anxious when someone else discarded some of these
items. This behavior had started about 20 years earlier and it worsened with
time. The garage, attic, and surroundings of his house were cluttered with these
objects. On admission, in the mental status examination, it was observed that the
patient was vigil, calm, and oriented; his mood was depressed; his speech was
organized, logic, and coherent; and there were no psychotic symptoms. A
psychotherapeutic plan was designed for the patient, including psychoeducation,
cognitive restructuring, and exposure to discarding objects. A pharmacological
treatment with fluvoxamine 100 mg tid and quetiapine 200 mg was added to the
therapeutic plan, with the progressive improvement of the symptoms. Nine months
later, the patient was able to sell/recycle most of the items. Studies evaluating
treatment for HD are necessary to improve the quality of life of the patients and
to reduce the hazards associated with the disorder.
PMID- 28701961
TI - Insights into the Development of the Adult Leydig Cell Lineage from Stem Leydig
Cells.
AB - Adult Leydig cells (ALCs) are the steroidogenic cells in the testes that produce
testosterone. ALCs develop postnatally from a pool of stem cells, referred to as
stem Leydig cells (SLCs). SLCs are spindle-shaped cells that lack steroidogenic
cell markers, including luteinizing hormone (LH) receptor and 3beta
hydroxysteroid dehydrogenase. The commitment of SLCs into the progenitor Leydig
cells (PLCs), the first stage in the lineage, requires growth factors, including
Dessert Hedgehog (DHH) and platelet-derived growth factor-AA. PLCs are still
spindle-shaped, but become steroidogenic and produce mainly androsterone. The
next transition in the lineage is from PLC to the immature Leydig cell (ILC).
This transition requires LH, DHH, and androgen. ILCs are ovoid cells that are
competent for producing a different form of androgen, androstanediol. The final
stage in the developmental lineage is ALC. The transition to ALC involves the
reduced expression of 5alpha-reductase 1, a step that is necessary to make the
cells to produce testosterone as the final product. The transitions along the
Leydig cell lineage are associated with the progressive down-regulation of the
proliferative activity, and the up-regulation of steroidogenic capacity, with
each step requiring unique regulatory signaling.
PMID- 28701964
TI - Teaching Quality in Math Class: The Development of a Scale and the Analysis of
Its Relationship with Engagement and Achievement.
AB - Math achievement and engagement declines in secondary education; therefore,
educators are faced with the challenge of engaging students to avoid school
failure. Within self-determination theory, we address the need to assess
comprehensively student perceptions of teaching quality that predict engagement
and achievement. In study one we tested, in a sample of 548 high school students,
a preliminary version of a scale to assess nine factors: teaching for relevance,
acknowledge negative feelings, participation encouragement, controlling language,
optimal challenge, focus on the process, class structure, positive feedback, and
caring. In the second study, we analyzed the scale's reliability and validity in
a sample of 1555 high school students. The scale showed evidence of reliability,
and with regard to criterion validity, at the classroom level, teaching quality
was a predictor of behavioral engagement, and higher grades were observed in
classes where students, as a whole, displayed more behavioral engagement. At the
within level, behavioral engagement was associated with achievement. We not only
provide a reliable and valid method to assess teaching quality, but also a method
to design interventions, these could be designed based on the scale items to
encourage students to persist and display more engagement on school duties, which
in turn bolsters student achievement.
PMID- 28701965
TI - The Depression Conundrum and the Advantages of Uncertainty.
AB - According to the WHO (2012), the prevalence of unipolar depressive disorders is
rising, even in those places where mental health treatments are widely available.
The WHO predicts that these disorders will be the leading contributor to the
global burden of disease by 2030. This sobering projection fits poorly with how
psychological treatments for depression are presented in the mainstream
scientific literature: as highly effective therapies, based upon a sound
understanding of the causes of distress. There is a clear discrepancy between the
rising prevalence figures on the one hand, and the confident claims of this
effectiveness research on the other. This discrepancy prompts a set of complex
interlinked questions, which we have called 'The Depression Conundrum.' In search
of a partial answer, the aim of our study was to critically analyze five meta
analytic studies investigating the effectiveness of psychological EBTs for
depression, all of which had been published in high impact factor journals. Our
examination established a number of methodological and statistical shortcomings
in every study. Furthermore, we argue that the meta-analytic technique is founded
upon problematic assumptions. The implications of our analysis are clear: decades
of quantitative research might not allow us to conclude that psychological EBTs
for depression are effective. The uncertainty and questions raised by our
findings might act as a catalyst to broaden the way in which depression and
associated therapies are researched. In addition, it might contribute toward a
more vigorous and interdisciplinary debate about how to tackle this soon-to-be
global public health priority number one.
PMID- 28701966
TI - Quantifying and Modeling Coordination and Coherence in Pedestrian Groups.
AB - Coherent collective behavior emerges from local interactions between individuals
that generate group dynamics. An outstanding question is how to quantify group
coordination of non-rhythmic behavior, in order to understand the nature of these
dynamics at both a local and global level. We investigate this problem in the
context of a small group of four pedestrians walking to a goal, treating their
speed, and heading as behavioral variables. To measure the local coordination
between pairs of pedestrians, we employ cross-correlation to estimate coupling
strength and cross-recurrence quantification (CRQ) analysis to estimate dynamic
stability. When compared to reshuffled virtual control groups, the results
indicate lower-dimensional behavior and a stronger, more stable coupling of
walking speed in real groups. There were no differences in heading alignment
observed between the real and virtual groups, due to the common goal. By modeling
the local speed coupling, we can simulate coordination at the dyad and group
levels. The findings demonstrate spontaneous coordination in pedestrian groups
that gives rise to coherent global behavior. They also offer a methodological
approach for investigating group dynamics in more complex settings.
PMID- 28701967
TI - A Novel Integrating Virtual Reality Approach for the Assessment of the Attachment
Behavioral System.
AB - Virtual reality (VR) technology represents a novel and powerful tool for
behavioral research in psychological assessment. VR provides simulated
experiences able to create the sensation of undergoing real situations. Users
become active participants in the virtual environment seeing, hearing, feeling,
and actuating as if they were in the real world. Currently, the most
psychological VR applications concern the treatment of various mental disorders
but not the assessment, that it is mainly based on paper and pencil tests. The
observation of behaviors is costly, labor-intensive, and it is hard to create
social situations in laboratory settings, even if the observation of actual
behaviors could be particularly informative. In this framework, social stressful
experiences can activate various behaviors of attachment for a significant person
that can help to control and soothe them to promote individual's well-being.
Social support seeking, physical proximity, and positive and negative behaviors
represent the main attachment behaviors that people can carry out during
experiences of distress. We proposed VR as a novel integrating approach to
measure real attachment behaviors. The first studies on attachment behavioral
system by VR showed the potentiality of this approach. To improve the assessment
during the VR experience, we proposed virtual stealth assessment (VSA) as a new
method. VSA could represent a valid and novel technique to measure various
psychological attributes in real-time during the virtual experience. The possible
use of this method in psychology could be to generate a more complete,
exhaustive, and accurate individual's psychological evaluation.
PMID- 28701968
TI - Perceived Enablers and Barriers to Optimal Health among Music Students: A
Qualitative Study in the Music Conservatoire Setting.
AB - Student health and wellbeing within higher education has been documented as poor
in relation to the general population. This is a particular problem among
students at music conservatoires, who are studying within a unique educational
context that is known to generate both physical and psychological challenges.
This article examines how conservatoire students experience health and wellbeing
within their institutional context, using a framework from health promotion to
focus attention on perceived enablers and barriers to optimal health in relation
to three levels: lifestyle, support services, and conservatoire environment. In
order to respond to the individuality of students' experiences, a qualitative
approach was taken based on semi-structured interviews with 20 current or recent
conservatoire students in the United Kingdom. Thematic analysis revealed a
complex set of enablers and barriers: (i) lifestyle enablers included value
placed on the importance of optimal health and wellbeing for musicians and daily
practices to enable this; lifestyle barriers included struggling to maintain
healthy lifestyles within the context of musical practice and learning; (ii)
support enablers included accessible support sources within and beyond the
conservatoire; support barriers included a perceived lack of availability or
awareness of appropriate support; (iii) environmental enablers included positive
and enjoyable experiences of performance as well as strong relationships and
communities; environmental barriers included experiences of comparison and
competition, pressure and stress, challenges with negative performance feedback,
psychological distress, and perceived overwork. The findings reveal a need for
health promotion to focus not only on individuals but also on the daily practices
and routines of conservatoires. Additionally, they suggest that continued work is
required to embed health and wellbeing support as an integral component of
conservatoire education, raising awareness so that all students are fully
informed of where, and how, to seek the information or help that they may need.
Finally, they indicate a need for more radical scrutiny of the cultures of
conservatoires and an assessment of how these can be modified to best optimize
students' health and wellbeing.
PMID- 28701969
TI - Feasibility and Efficacy of Prolonged Exposure for PTSD among Individuals with a
Psychotic Spectrum Disorder.
AB - Objective: Few empirical studies have examined the feasibility of trauma-focused
treatment among individuals with schizophrenia. This lack of research is
important given the substantial overlap of trauma exposure and subsequent PTSD
with psychotic spectrum disorders, and the potential for PTSD to complicate the
course and prognosis of schizophrenia and other variants of severe mental
illness. Method: As part of a larger study, 14 veterans with a psychotic spectrum
disorder were enrolled to receive prolonged exposure (PE) for PTSD within a
single arm open trial study design. Patient reactions and responses to PE were
examined using feasibility indices such as attrition, survey reactions, and
treatment expectancy; pre and post-changes in PTSD severity and diagnostic
status; and thematic interviews conducted post-intervention. Results:
Quantitative and qualitative data indicate that implementation of PE is feasible,
subjectively well-tolerated, and may result in clinically significant reductions
in PTSD symptoms in patients with psychotic spectrum disorders. Conclusion:
Consistent with treatment outcome data in clinical populations with a broader
range of severe mental illnesses, the current results support the use of PTSD
exposure-based interventions, such as PE, for individuals with psychotic spectrum
disorders.
PMID- 28701970
TI - The "Depressive" Attributional Style Is Not That Depressive for Buddhists.
AB - Numerous studies have shown that depression-prone people are characterized by a
chronic style of attributing failures to internal, stable, and global causes,
sometimes labeled as the "depressive attributional style." Much less is known,
however, about how social-cultural factors such as religious beliefs might
modulate these processes. In the current study, we hypothesized that Buddhism's
view of ultimate internal controllability plays a buffering role against the
depressive attributional style and reduces its negative impacts. We administrated
measures of attributional styles and psychological adjustments to a sample of
Chinese Buddhists as well as a control group recruited in China. Data analyses
showed that Buddhists were more likely to attribute bad outcomes to internal,
stable, and global causes, but their well-being was less affected by it. Thus,
these results indicate that the "depressive" attributional style is not that
depressive for Buddhists, after all.
PMID- 28701971
TI - Facilitating Social Play for Children with PDDs: Effects of Paired Robotic
Devices.
AB - Interacting with toys and other people is fundamental for developing social
communication skills. However, children with autism spectrum disorder (ASD) are
characterized by having a significant impairment in social interaction, which
often leads to deficits in play skills. For this reason, methods of teaching play
skills to young children with ASD have been well documented. Although previous
studies have examined a variety of instructional strategies for teaching skills,
few studies have evaluated the potential of using robotic devices. The purpose of
the present study is to examine whether automatic feedback provided by colored
lights and vibration via paired robotic devices, COLOLO, facilitates social play
behaviors in children with ASD. We also explore how social play relates to social
interaction. COLOLO is a system of paired spherical devices covered with soft
fabric. All participants in this study were recruited as volunteers through the
Department of Psychology at Keio University. The pilot study included three
participants diagnosed with Pervasive Developmental Disorders (PDDs; 5- to 6-year
old boys), and compared experimental conditions with and without automatic
feedback from the devices (colored lights and vibration). The results indicated
that the participants in the condition that included feedback from the devices
exhibited increased rates of ball contact and looking at the therapist's ball,
but did not exhibit increased rates of eye contact or positive affect. In the
experimental study, a systematic replication of the pilot study was performed
with three other participants diagnosed with PDDs (3- to 6-year-old boys), using
an A-B-A-B design. Again, the results demonstrated that, in the condition with
colored lights and vibration, the children increased ball contact as well as
looking at the therapist's ball. However, the results did not show the effect of
automatic feedback consistently for three children. These findings are discussed
in terms of the potential of paired robotic devices as a method to facilitate
social play for children with ASD.
PMID- 28701972
TI - The Effects of a Normal Rate versus a Slow Intervalled Rate of Oral Nutrient
Intake and Intravenous Low Rate Macronutrient Application on Psychophysical
Function - Two Pilot Studies.
AB - Stomach distension and energy per time are factors influencing satiety. Moreover,
different rates of nutrient intake induce different stomach distension. The goal
of our studies was to elucidate the influence of different oral rates of nutrient
intake (normal rate versus slow intervalled rate; study I) and intravenous low
rate macronutrient application (protein, carbohydrate, fat) or placebo (study II)
on psychophysical function. The pilot studies investigated the effects of 1)
study I: a mixed nutrient solution (1/3 protein, 1/3 fat, 1/3 carbohydrates) 2)
study II: intravenous macronutrient infusions (protein, carbohydrate, fat) or
placebo on psychophysical function (mood, hunger, food craving, alertness, smell
intensity ratings and hedonic ratings) in human subjects. In study I 10 male
subjects (age range: 21-30 years) completed the study protocol participating in
both test conditions and in study II 20 male subjects (age range: 19-41 years)
completed the study protocol participating in all test conditions. Additionally,
metabolic function was analyzed and cognitive and olfactory tests were conducted
twice starting 100 min before the beginning of the intervention and 240 min
after. Psychophysical (mood, hunger, fat-, protein-, carbohydrate-, sweets- and
vegetable-craving), alertness and metabolic function tests were performed seven
times on each examination day. Greater effects on hunger and food cravings were
observed for normal rate of intake compared to slow intervalled rate of intake
and intravenous low rate macronutrient application. Our findings potentially
confirm that volume of the food ingested and a higher rate of energy per time
contribute to satiety during normal rate of food intake, while slow intervalled
rate of food intake and intravenous low rate macronutrient application showed no
effects on satiation. Our results motivate the view that a certain amount of
volume of the food ingested and a certain energy per time ratio are necessary to
reduce hunger and food craving.
PMID- 28701973
TI - Schizophrenia: An Impairment in the Capacity to Perceive Affordances.
AB - Phenomenological psychopathologists conceptualize schizophrenia as a self
disorder involving profound distortions of selfhood. For James Gibson, "to
perceive the world is to coperceive oneself." If the sense of self is disturbed
in individuals with schizophrenia, this could also lead to disturbances in these
individuals' ability to perceive affordances, environmental properties taken with
reference to the perceiver's action capabilities (e.g., a rigid surface affording
'walk-on-able,' chairs 'sit-on-able,' and so on). To test this hypothesis, three
experiments investigated schizophrenia patients' affordance perception.
Participants were presented with a photo of a common object on the computer and
then asked to judge its secondary affordance (a non-designed function) in a two
choice reaction time task in Experiment 1 and in a yes/no task in Experiment 2.
Schizophrenia participants performed less accurately and more slowly than
controls. To rule out visual impairment as a contributing factor, in Experiment
3, participants identified physical properties (color, shape, material
composition) of the objects. Schizophrenia participants were as accurate as
controls and responded faster than in the previous experiments. Results suggest
that the capacity to perceive affordances is likely impaired in people with
schizophrenia, although the capacity to detect the object's physical properties
is kept intact. Inability to perceive affordances, those functionally significant
properties of the surrounding environment, may help explain why schizophrenia
patients may appear as somewhat detached from the world.
PMID- 28701974
TI - Substance Use among Adolescents Involved in Bullying: A Cross-Sectional
Multilevel Study.
AB - Being involved in bullying as a victim or perpetrator could have deleterious
health consequences. Even though there is some evidence that bullies and victims
of bullying have a higher risk for drug use, less is known about bystanders. The
aim of this research was to study the association between bullying experience (as
victims, bullies, or bystanders) and substance use. We gathered complete
information from a nationally representative sample of 36,687 students (51.4%
female) attending 756 schools in Chile. We used a self-reported questionnaire
which was developed based on similar instruments used elsewhere. This
questionnaire was piloted and presented to an expert panel for approval. We used
multilevel multivariate logistic regression analyses, controlling for several
variables at the individual (e.g., school membership, parental monitoring) and
school levels (e.g., school type, school denomination). This study shows that
bullies and bully-victims have a high risk for cigarette, alcohol, and cannabis
use than bystanders. This is one of the few studies exploring the association
between witnessing bullying and substance use. These findings add new insights to
the study of the co-occurrence of bullying and substance use. Other factors, such
as higher academic performance, stronger school membership, and better parental
monitoring reduced the risk of any substance use, while the experience of
domestic violence and the perception of social disorganization in the
neighborhood, increased the risk. These findings may help the design of
preventive interventions.
PMID- 28701975
TI - To Pass or Not to Pass: Modeling the Movement and Affordance Dynamics of a Pick
and Place Task.
AB - Humans commonly engage in tasks that require or are made more efficient by
coordinating with other humans. In this paper we introduce a task dynamics
approach for modeling multi-agent interaction and decision making in a pick and
place task where an agent must move an object from one location to another and
decide whether to act alone or with a partner. Our aims were to identify and
model (1) the affordance related dynamics that define an actor's choice to move
an object alone or to pass it to their co-actor and (2) the trajectory dynamics
of an actor's hand movements when moving to grasp, relocate, or pass the object.
Using a virtual reality pick and place task, we demonstrate that both the
decision to pass or not pass an object and the movement trajectories of the
participants can be characterized in terms of a behavioral dynamics model.
Simulations suggest that the proposed behavioral dynamics model exhibits features
observed in human participants including hysteresis in decision making, non
straight line trajectories, and non-constant velocity profiles. The proposed
model highlights how the same low-dimensional behavioral dynamics can operate to
constrain multiple (and often nested) levels of human activity and suggests that
knowledge of what, when, where and how to move or act during pick and place
behavior may be defined by these low dimensional task dynamics and, thus, can
emerge spontaneously and in real-time with little a priori planning.
PMID- 28701976
TI - A Latent Factor Analysis of Working Memory Measures Using Large-Scale Data.
AB - Working memory (WM) is a key cognitive system that is strongly related to other
cognitive domains and relevant for everyday life. However, the structure of WM is
yet to be determined. A number of WM models have been put forth especially by
factor analytical studies. In broad terms, these models vary by their emphasis on
WM contents (e.g., visuospatial, verbal) vs. WM processes (e.g., maintenance,
updating) as critical, dissociable elements. Here we conducted confirmatory and
exploratory factor analyses on a broad set of WM tasks, half of them numerical
verbal and half of them visuospatial, representing four commonly used task
paradigms: simple span, complex span, running memory, and n-back. The tasks were
selected to allow the detection of both content-based (visuospatial, numerical
verbal) and process-based (maintenance, updating) divisions. The data were
collected online which allowed the recruitment of a large and demographically
diverse sample of adults (n = 711). Both factor analytical methods pointed to a
clear division according to task content for all paradigms except n-back, while
there was no indication for a process-based division. Besides the content-based
division, confirmatory factor analyses supported a model that also included a
general WM factor. The n-back tasks had the highest loadings on the general
factor, suggesting that this factor reflected high-level cognitive resources such
as executive functioning and fluid intelligence that are engaged with all WM
tasks, and possibly even more so with the n-back. Together with earlier findings
that indicate high variability of process-based WM divisions, we conclude that
the most robust division of WM is along its contents (visuospatial vs. numerical
verbal), rather than along its hypothetical subprocesses.
PMID- 28701977
TI - Foreign Languages Sound Fast: Evidence from Implicit Rate Normalization.
AB - Anecdotal evidence suggests that unfamiliar languages sound faster than one's
native language. Empirical evidence for this impression has, so far, come from
explicit rate judgments. The aim of the present study was to test whether such
perceived rate differences between native and foreign languages (FLs) have
effects on implicit speech processing. Our measure of implicit rate perception
was "normalization for speech rate": an ambiguous vowel between short /a/ and
long /a:/ is interpreted as /a:/ following a fast but as /a/ following a slow
carrier sentence. That is, listeners did not judge speech rate itself; instead,
they categorized ambiguous vowels whose perception was implicitly affected by the
rate of the context. We asked whether a bias towards long /a:/ might be observed
when the context is not actually faster but simply spoken in a FL. A fully
symmetrical experimental design was used: Dutch and German participants listened
to rate matched (fast and slow) sentences in both languages spoken by the same
bilingual speaker. Sentences were followed by non-words that contained vowels
from an /a-a:/ duration continuum. Results from Experiments 1 and 2 showed a
consistent effect of rate normalization for both listener groups. Moreover, for
German listeners, across the two experiments, foreign sentences triggered more
/a:/ responses than (rate matched) native sentences, suggesting that foreign
sentences were indeed perceived as faster. Moreover, this FL effect was modulated
by participants' ability to understand the FL: those participants that scored
higher on a FL translation task showed less of a FL effect. However, opposite
effects were found for the Dutch listeners. For them, their native rather than
the FL induced more /a:/ responses. Nevertheless, this reversed effect could be
reduced when additional spectral properties of the context were controlled for.
Experiment 3, using explicit rate judgments, replicated the effect for German but
not Dutch listeners. We therefore conclude that the subjective impression that
FLs sound fast may have an effect on implicit speech processing, with
implications for how language learners perceive spoken segments in a FL.
PMID- 28701978
TI - Academic Achievement in Physics-Chemistry: The Predictive Effect of Attitudes and
Reasoning Abilities.
AB - Science education plays a critical role as political priority due to its
fundamental importance in engaging students to pursue technological careers
considered essential in modern societies, in order to face scientific development
challenges. High-level achievement on science education and positive attitudes
toward science constitutes a crucial challenge for formal education. Several
studies indicate close relationships between students' attitudes, cognitive
abilities, and academic achievement. The main purpose of this study is to analyze
the impact of student's attitudes toward the school discipline of Physics and
Chemistry and their reasoning abilities on academic achievement on that school
subject, among Portuguese 9th grade students using the data collected during the
Project Academic Performance and Development: a longitudinal study on the effects
of school transitions in Portuguese students (PTDC/CPE-CED/104884/2008). The
participants were 470 students (267 girls - 56.8% and 203 boys - 43.2%), aged 14
16 years old (MU = 14.3 +/- 0.58). The attitude data were collected using the
Attitude toward Physics-Chemistry Questionnaire (ATPCQ) and, the Reasoning Test
Battery (RTB) was used to assess the students reasoning abilities. Achievement
was measured using the students' quarterly (9-week) grades in the physics and
chemistry subject. The relationships between the attitude dimensions toward
Physics-chemistry and the reasoning dimensions and achievement in each of the
three school terms were assessed by multiple regression stepwise analyses and
standardized regression coefficients (beta), calculated with IBM SPSS Statistics
21 software. Both variables studied proved to be significant predictor variables
of school achievement. The models obtained from the use of both variables were
always stronger accounting for higher proportions of student's grade variations.
The results show that ATPCQ and RTB had a significantly positive relationship
with student's achievement in Physics-chemistry, indicating that both attitudinal
and cognitive variables should be taken into account on science education as well
as in educative intervention.
PMID- 28701979
TI - Protecting the Environment for Self-interested Reasons: Altruism Is Not the Only
Pathway to Sustainability.
AB - Concerns for environmental issues are important drivers of sustainable and pro
environmental behaviors, and can be differentiated between those with a self
enhancing (egoistic) vs. self-transcendent (biospheric) psychological foundation.
Yet to date, the dominant approach for promoting pro-environmental behavior has
focused on highlighting the benefits to others or nature, rather than appealing
to self-interest. Building on the Inclusion Model for Environmental Concern, we
argue that egoistic and biospheric environmental concerns, respectively,
conceptualized as self-interest and altruism, are hierarchically structured, such
that altruism is inclusive of self-interest. Three studies show that self
interested individuals will behave more pro-environmentally when the behavior
results in a personal benefit (but not when there is exclusively an environmental
benefit), while altruistic individuals will engage in pro-environmental behaviors
when there are environmental benefits, and critically, also when there are
personal benefits. The reported findings have implications for programs and
policies designed to promote pro-environmental behavior, and for social science
research aimed at understanding human responses to a changing environment.
PMID- 28701980
TI - Depression and Anxiety Prevention Based on Cognitive Behavioral Therapy for At
Risk Adolescents: A Meta-Analytic Review.
AB - Depression and anxiety disorders are among the most common mental disorders
during adolescence. During this life phase, the incidence of these clinical
disorders rises dramatically, and even more adolescents suffer from symptoms of
depression or anxiety that are just below the clinical threshold. Both clinical
and subclinical levels of depression or anxiety symptoms are related to decreased
functioning in various areas, such as social and academic functioning. Prevention
of depression and anxiety in adolescents is therefore imperative. We conducted a
meta-analytic review of the effects of school-based and community-based
prevention programs that are based on cognitive behavioral therapy with the
primary goal preventing depression, anxiety, or both in high risk adolescents.
Articles were obtained by searching databases and hand searching reference lists
of relevant articles and reviews. The selection process yielded 32 articles in
the meta-analyses. One article reported on two studies and three articles
reported on both depression and anxiety. This resulted in a total of 36 studies,
23 on depression and 13 on anxiety. For depression prevention aimed at high risk
adolescents, meta-analysis showed a small effect of prevention programs directly
after the intervention, but no effect at 3-6 months and at 12 months follow-up.
For anxiety prevention aimed at high risk adolescents, no short-term effect was
found, nor at 12 months follow-up. Three to six months after the preventive
intervention, symptoms of anxiety were significantly decreased. Although effects
on depression and anxiety symptoms were small and temporary, current findings
cautiously suggest that depression and anxiety prevention programs based on CBT
might have small effects on mental health of adolescents. However, it also
indicates that there is still much to be gained for prevention programs. Current
findings and possibilities for future research are discussed in order to further
improve the effectiveness of targeted prevention on internalizing disorders.
PMID- 28701981
TI - Language Mediated Concept Activation in Bilingual Memory Facilitates Cognitive
Flexibility.
AB - This is the first attempt of empirical investigation of language mediated concept
activation (LMCA) in bilingual memory as a cognitive mechanism facilitating
divergent thinking. Russian-English bilingual and Russian monolingual college
students were tested on a battery of tests including among others Abbreviated
Torrance Tests for Adults assessing divergent thinking traits and translingual
priming (TLP) test assessing the LMCA. The latter was designed as a lexical
decision priming test, in which a prime and a target were not related in Russian
(language of testing), but were related through their translation equivalents in
English (spoken only by bilinguals). Bilinguals outperformed their monolingual
counterparts on divergent thinking trait of cognitive flexibility, and
bilinguals' performance on this trait could be explained by their TLP effect. Age
of second language acquisition and proficiency in this language were found to
relate to the TLP effect, and therefore were proposed to influence the
directionality and strength of connections in bilingual memory.
PMID- 28701982
TI - Negative Self-Disclosure on the Web: The Role of Guilt Relief.
AB - In this paper, we suggest people use anonymous online forums as platforms for
self-disclosing actions they feel guilty about-such as transgressions and
unethical behaviors-with the goal of achieving guilt relief through others'
reactions. We support this proposition by analyzing field data extracted from
Yahoo Answers, an online question-and-answer website. Our analysis shows the
level of guilt relief an answer is expected to offer the "asker" (the self
disclosing person) is positively associated with the asker's likelihood of
selecting that answer as the "best" response to the self-disclosure. Furthermore,
following receipt of a guilt-relieving answer, an asker becomes less likely to
engage in prosocial behavior, which is another type of guilt-relieving action.
PMID- 28701983
TI - Acquiring the Impossible: Developmental Stages of Copredication.
AB - Much is known about the acquisition of phonological competence and lexical
categories, but there has been substantially less research into word meaning
development. In an attempt to contribute to this debate, a group of 24 children
aged 4-11 were asked to define a set of words, as were a group of 12 adult
controls. The stimuli included both concrete and abstract words, in particular
words exhibiting a rare form of polysemy known as copredication, which permits
the simultaneous attribution of concrete and abstract senses to a single nominal,
creating an 'impossible' entity. The results were used to track the developmental
trajectory of copredication, previously unexplored in the language acquisition
literature.
PMID- 28701984
TI - Is there a Competition between Functional and Situational Affordances during
Action Initiation with Everyday Tools?
AB - Most studies of human-tool interactions focus on the typical use of a tool (e.g.,
cutting in the case of a knife). However, little is known about situations
requiring atypical tool use (e.g., using a knife to tighten a screw). The present
study focused on a selection of atypical uses of everyday tools which might be in
conflict with their typical use. Our objective was to study how tool function
influences the selection of the relevant action. In Experiment 1, which involved
visuomotor priming, two everyday tools (a knife and a screwdriver) and two
neutral tools (two bars, with no strong functional affordance) were used as
primes and targets. Participants had to use the target with the appropriate box
(indicated by the color) that allowed to make an action. Longer initiation times
were observed when the prime was an everyday tool, irrespective of the nature of
the target. We therefore observed a conflict between functional and situational
affordances. To investigate whether the priming effect is caused by the task
irrelevance of the prime, we asked the participants in Experiment 2 to perform an
action associated with the prime. The results showed longer initiation times only
when the prime and target were everyday tools, irrespective of their precise
nature. This suggests that activation of the typical use of a tool might not be
fully automatic but flexible depending on the situation.
PMID- 28701985
TI - Retrieval Practice Fails to Insulate Episodic Memories against Interference after
Stroke.
AB - Recent work in cognitive psychology showed that retrieval practice of previously
studied information can insulate this information against retroactive
interference from subsequently studied other information in healthy individuals.
The present study examined whether this beneficial effect of interference
reduction is also present in patients with stroke. Twenty-two patients with
stroke, 4.6 months post injury on average, and 22 healthy controls participated
in the experiment. In each of two experimental sessions, participants first
studied a list of items (list 1) and then underwent a practice phase in which the
list 1 items were either restudied or retrieval practiced. Participants then
either studied a second list of items (list 2) or fulfilled an unrelated
distractor task. Recall of the two lists' items was assessed in a final criterion
test. Results showed that, in healthy controls, additional study of list 2 items
impaired final recall of list 1 items in the restudy condition but not in the
retrieval practice condition. In contrast, in patients with stroke, list 2
learning impaired final list 1 recall in both conditions. The results indicate
that retrieval practice insulated the tested information against retroactive
interference in healthy controls, but failed to do so in patients with stroke.
Possible implications of the findings for the understanding of long-term memory
impairment after stroke are discussed.
PMID- 28701986
TI - Controlling the Anchoring Effect through Transcranial Direct Current Stimulation
(tDCS) to the Right Dorsolateral Prefrontal Cortex.
AB - Selective accessibility mechanisms indicate that anchoring effects are results of
selective retrieval of working memory. Neuroimaging studies have revealed that
the right dorsolateral prefrontal cortex (DLPFC) is closely related to memory
retrieval and performance. However, no research has investigated the effect of
changing the cortical excitability in right DLPFC on anchoring effects.
Transcranial direct current stimulation (tDCS) can modulate the excitability of
the human cerebral cortex, while anodal and cathodal tDCS are postulated to
increase or decrease cortical activity, respectively. In this study, we used tDCS
to investigate whether effects of increased or decreased right DLPFC excitability
influence anchoring effects in willingness to pay (WTP) experiments. Ninety
participants were first randomly assigned to receive either anodal, cathodal, or
sham stimulation of 15 min, then they performed a valuation task regarding WTP.
The results showed that anchoring effects were negatively related to activities
of right DLPFC: the anodal stimulation diminished anchoring effects while the
cathodal stimulation increased anchoring effects. These outcomes provide one of
the first instances of neural evidence for the role of the right DLPFC in
anchoring effects and support psychological explanations of the selective
accessibility mechanisms and cognitive sets.
PMID- 28701987
TI - A Comparison of English and Mandarin-Speaking Preschool Children's Imitation of
Motion Events.
AB - Typically in English, a "satellite-framed" language, manner is expressed in the
verb and path is expressed in supporting words. Past studies using looking time
techniques suggest that English-speaking 3-year-olds show language-specific
action processing, but 2.5-year-olds preferentially attend to path regardless of
native language. In Study 1, we test whether language-specific action component
preferences will be reflected in children's imitation, as a more explicit
measure. Children who spoke English saw an adult move an object along a series of
platforms using one of two paths and manners. Then, the children were given the
opportunity to move the object on a different test platform, which was designed
to force them to choose to reproduce either the demonstrated path or the manner.
The results showed that 3-year-olds, but not 2.5-year-olds, were more likely to
imitate the manner versus the path. In Study 2, we extend the investigation to a
less commonly studied language within this domain, Mandarin. Typically in
Mandarin, an "equipollently framed" language, both manner and path are expressed
within equally significant verbs. The results indicated that 3-year-olds did not
show a consistent preference to imitate either the path or the manner. In
contrast, 2.5-year-olds were more likely to imitate the path than the manner.
This research highlights the potential for the imitation choice paradigm, as an
explicit measure, to understand how language affects cognition, and suggests a
new language-specific pattern in action interpretation.
PMID- 28701988
TI - ENED-GEM: A Conceptual Framework Model for Psychological Enjoyment Factors and
Learning Mechanisms in Educational Games about the Environment.
AB - Based on a thorough review of psychological literature, this article seeks to
develop a model of game enjoyment and environmental learning (ENvironmental
EDucational Game Enjoyment Model, ENED-GEM) and delineate psychological processes
that might facilitate learning and inspire behavioral change from educational
games about the environment. A critically acclaimed digital educational game
about environmental issues (Fate of the World by Red Redemption/Soothsayer Games)
was used as a case study. Two hundred forty-nine reviews of the game from the
popular gaming and reviewing platform known as Steam were analyzed by means of a
thematic content analysis in order to identify key player enjoyment factors
believed to be relevant to the process of learning from games, as well as to gain
an understanding of positive and negative impressions about the game's general
content. The end results of the thematic analysis were measured up to the
suggested ENED-GEM framework. Initial results generally support the main elements
of the ENED-GEM, and future research into the importance of these individual core
factors is outlined.
PMID- 28701989
TI - Supramodal Enhancement of Auditory Perceptual and Cognitive Learning by Video
Game Playing.
AB - Medical rehabilitation involving behavioral training can produce highly
successful outcomes, but those successes are obtained at the cost of long periods
of often tedious training, reducing compliance. By contrast, arcade-style video
games can be entertaining and highly motivating. We examine here the impact of
video game play on contiguous perceptual training. We alternated several periods
of auditory pure-tone frequency discrimination (FD) with the popular spatial
visual-motor game Tetris played in silence. Tetris play alone did not produce any
auditory or cognitive benefits. However, when alternated with FD training it
enhanced learning of FD and auditory working memory. The learning-enhancing
effects of Tetris play cannot be explained simply by the visual-spatial training
involved, as the effects were gone when Tetris play was replaced with another
visual-spatial task using Tetris-like stimuli but not incorporated into a game
environment. The results indicate that game play enhances learning and transfer
of the contiguous auditory experiences, pointing to a promising approach for
increasing the efficiency and applicability of rehabilitative training.
PMID- 28701990
TI - Mandarin-Speaking Children's Speech Recognition: Developmental Changes in the
Influences of Semantic Context and F0 Contours.
AB - The goal of this developmental speech perception study was to assess whether and
how age group modulated the influences of high-level semantic context and low
level fundamental frequency (F0) contours on the recognition of Mandarin speech
by elementary and middle-school-aged children in quiet and interference
backgrounds. The results revealed different patterns for semantic and F0
information. One the one hand, age group modulated significantly the use of F0
contours, indicating that elementary school children relied more on natural F0
contours than middle school children during Mandarin speech recognition. On the
other hand, there was no significant modulation effect of age group on semantic
context, indicating that children of both age groups used semantic context to
assist speech recognition to a similar extent. Furthermore, the significant
modulation effect of age group on the interaction between F0 contours and
semantic context revealed that younger children could not make better use of
semantic context in recognizing speech with flat F0 contours compared with
natural F0 contours, while older children could benefit from semantic context
even when natural F0 contours were altered, thus confirming the important role of
F0 contours in Mandarin speech recognition by elementary school children. The
developmental changes in the effects of high-level semantic and low-level F0
information on speech recognition might reflect the differences in auditory and
cognitive resources associated with processing of the two types of information in
speech perception.
PMID- 28701991
TI - An Arterial Spin Labeling MRI Perfusion Study of Migraine without Aura Attacks.
AB - BACKGROUND: Studies of brain perfusion during migraine without aura attacks have
inconsistent results. METHODS: Arterial spin labeling MRI, a non-invasive
quantitative perfusion technique, was used to prospectively study a spontaneous
untreated migraine without aura attack and a headache-free period. Image analysis
used FSL and MATLAB software; Group analysis used permutation methods for
perfusion differences between sessions. RESULTS: Thirteen women (age 35.7) were
scanned during an attack of an average intensity of 6.8 (on 0-10 Visual Analog
Scale) and 16 h duration. No global or regional perfusion differences were
identified when comparing migraine and migraine-free sessions. DISCUSSION: Our
findings suggest that the painful phase of migraine without aura attacks is not
associated with brain perfusion abnormalities.
PMID- 28701992
TI - Verifying the Relative Efficacy between Continuous Positive Airway Pressure
Therapy and Its Alternatives for Obstructive Sleep Apnea: A Network Meta
analysis.
AB - Obstructive sleep apnea (OSA) is a common breathing disorder, and continuous
positive airway pressure (CPAP) therapy together with its alternatives has been
developed to treat this disease. This network meta-analysis (NMA) was aimed to
compare the efficacy of treatments for OSA. Cochrane Library, MEDLINE, and Embase
were searched for eligible studies. A conventional and NMA was carried out to
compare all therapies. Sleeping characteristics, including Apnea-Hypopnea Index
(AHI), Epworth Sleepiness Scale (ESS), arterial oxygen saturation, and arousal
index (AI), and changes of blood pressure were selected as outcomes. A total of
84 studies were finally included after rigorous screenings. For the primary
outcomes of AHI and ESS, the value of auto-adjusting positive airway pressure
(APAP), CPAP, and oral appliance (OA) all showed statistically reduction compared
with inactive control (IC). Similar observation was obtained in AI, with
treatments of the three active interventions. A lower effect of IC in SaO2 was
exhibited when compared with APAP, CPAP, and OA. Similar statistically
significant results were presented in 24 h systolic blood pressure and 24 h DBP
when comparing with CPAP. Our NMA identified CPAP as the most efficacious
treatment for OSA patients after the evaluation of sleeping characteristics and
blood pressures. In addition, more clinical trials are needed for further
investigation due to the existence of inconsistency observed in this study.
PMID- 28701993
TI - No Impaired Glucose Tolerance in Primary Insomnia Patients with Normal Results of
Polysomnography.
AB - BACKGROUND: According to recent studies, sleep restriction and disruption both
have a prominent negative influence on glucose metabolism. This could also be
shown in sleep disorders, such as sleep apnea and the restless legs syndrome.
However, similar studies regarding insomnia have not been that consistent, yet.
Moreover, most previous studies did not include objective polysomnography (PSG)
data. METHODS: Patients with primary insomnia (N = 17) and healthy controls (N =
15) were investigated using psychometric tests such as the Epworth Sleepiness
Scale and the Pittsburgh sleep quality index (PSQI). Two nights of full PSG were
performed in all subjects, and after the first PSG night subjects underwent a
standard oral glucose tolerance test (OGTT). PSG-, arousal-, and glucose
metabolism-parameters were compared between groups. RESULTS: Patients with
insomnia were, as expected, sleepier than healthy controls and showed higher PSQI
values. All PSG parameters, however, including parameters related to nocturnal
arousals, did not differ between groups. Moreover, OGGT results and all other
parameters of glucose tolerance were not different between insomniac patients and
healthy controls. CONCLUSION: Our findings suggest that glucose tolerance is not
impaired in patients with chronic insomnia and normal PSG-findings. Therefore,
impaired glucose metabolism and diabetes related to insomnia in earlier studies
might be restricted to those patients who have objectively disturbed sleep.
PMID- 28701994
TI - The Role of Substance P in Secondary Pathophysiology after Traumatic Brain
Injury.
AB - It has recently been shown that substance P (SP) plays a major role in the
secondary injury process following traumatic brain injury (TBI), particularly
with respect to neuroinflammation, increased blood-brain barrier (BBB)
permeability, and edema formation. Edema formation is associated with the
development of increased intracranial pressure (ICP) that has been widely
associated with increased mortality and morbidity after neurotrauma. However, a
pharmacological intervention to specifically reduce ICP is yet to be developed,
with current interventions limited to osmotic therapy rather than addressing the
cause of increased ICP. Given that previous publications have shown that SP, NK1
receptor antagonists reduce edema after TBI, more recent studies have examined
whether these compounds might also reduce ICP and improve brain oxygenation after
TBI. We discuss the results of these studies, which demonstrate that NK1
antagonists reduce posttraumatic ICP to near normal levels within 4 h of drug
administration, as well as restoring brain oxygenation to near normal levels in
the same time frame. The improvements in these parameters occurred in association
with an improvement in BBB integrity to serum proteins, suggesting that SP
mediated increases in vascular permeability significantly contribute to the
development of increased ICP after acute brain injury. NK1 antagonists may
therefore provide a novel, mechanistically targeted approach to the management of
increased ICP.
PMID- 28701995
TI - Cerebellar Dysfunction in Multiple Sclerosis.
AB - Multiple sclerosis (MS) commonly affects the cerebellum causing acute and chronic
symptoms. Cerebellar signs contribute significantly to clinical disability, and
symptoms such as tremor, ataxia, and dysarthria are particularly difficult to
treat. Increasing knowledge concerning the pathophysiology of cerebellar disease
in MS from human postmortem studies, experimental models, and clinical trials has
raised the hope that cerebellar symptoms will be better treated in the future.
PMID- 28701996
TI - Aberrant Pyramidal Tract in Comparison with Pyramidal Tract on Diffusion Tensor
Tractography: A Mini-Review.
AB - The pyramidal tract (PT) is a major neural tract that controls voluntary
movements in the human brain. The PT has several collateral pathways, including
the aberrant pyramidal tract (APT), which passes through the medial lemniscus
location at the midbrain and pons. Diffusion tensor tractography (DTT) allows
visualization and estimation of the APT in three dimensions. In this mini-review,
eight DTT studies on the APT were reviewed. Two studies for normal subjects
reported the prevalence (17-18% of hemispheres) and the different characteristics
(different cortical origin, less directionality, and fewer neural fibers) of the
APT compared with the PT. Six studies reported on the APT in patients with
cerebral infarct, traumatic brain injury, and cerebral palsy and suggested that
the APT could contribute to motor recovery following brain injury. The research
on the APT in patients with brain injury has important implications for neuro
rehabilitation because understanding of the motor recovery mechanism can provide
the basis for scientific rehabilitation strategies. Therefore, studies involving
various brain pathologies with large numbers of patients on this topic should be
encouraged. In addition, further studies are needed on the exact role of the APT
in normal subjects.
PMID- 28701997
TI - Early Intranasal Vasopressin Administration Impairs Partner Preference in Adult
Male Prairie Voles (Microtus ochrogaster).
AB - Research supports a modulatory role for arginine vasopressin (AVP) in the
expression of socially motivated behaviors in mammals. The acute effects of AVP
administration are demonstrably pro-social across species, providing the
justification for an ever-increasing measure of clinical interest over the last
decade. Combining these results with non-invasive intranasal delivery results in
an attractive system for offering intranasal AVP (IN-AVP) as a therapeutic for
the social impairments of children with autism spectrum disorder. But, very
little is known about the long-term effects of IN-AVP during early development.
In this experiment, we explored whether a single week of early juvenile
administration of IN-AVP (low = 0.05 IU/kg, medium = 0.5 IU/kg, high = 5.0 IU/kg)
could impact behavior across life in prairie voles. We found increases in fecal
boli production during open field and novel object recognition testing for the
medium dose in both males and females. Medium-dose females also had significantly
more play bouts than control when exposed to novel conspecifics during the
juvenile period. Following sexual maturity, the medium and high doses of IN-AVP
blocked partner preference formation in males, while no such impairment was found
for any of the experimental groups in females. Finally, the high-dose selectively
increased adult male aggression with novel conspecifics, but only after extended
cohabitation with a mate. Our findings confirm that a single week of early IN-AVP
treatment can have organizational effects on behavior across life in prairie
voles. Specifically, the impairments in pair-bonding behavior experienced by male
prairie voles should raise caution when the prosocial effects of acute IN-AVP
demonstrated in other studies are extrapolated to long-term treatment.
PMID- 28701998
TI - Thyroid Autoimmunity and Lichen.
AB - Lichen planus (LP) and lichen sclerosus (LS) are cutaneous-mucous diseases with
uncertain epidemiology. Current data, which are likely to be underestimated,
suggest a prevalence in the general population of 0.1-4% for cutaneous LP, 1.27
2.0% for oral LP, and 0.1-3.3% for LS. While etiology of lichen is still unknown,
clinical and histological evidence show an (auto)immune pathogenesis. Association
of lichen with autoimmune thyroid disease (AITD) has been investigated in few
studies. This association appears better defined in the case of LS, while is more
controversial for LP. In both situations, the frequency of the association is
higher in females. We review the available literature on the correlation between
the different types of lichen and AITD, and the literature on the genetic risk
factors which are shared by both conditions. Such data suggest that a common
pathogenic mechanism could be the cause for co-occurrence of lichen and AITD, at
least in some patients. Additionally, analyzing literature data and in continuity
with our previous work on other autoimmune diseases, we suggest that molecular
mimicry could trigger both diseases, and thus explain their co-occurrence.
PMID- 28701999
TI - Incubation Temperature, But Not Pequi Oil Supplementation, Affects Methane
Production, and the Ruminal Microbiota in a Rumen Simulation Technique (Rusitec)
System.
AB - Lipid supplementation is a promising strategy for methane mitigation in cattle
and has been evaluated using several different lipid sources. However, limited
studies have assessed the effect of temperature on methane emissions from cattle
and changes in incubation temperature have also not been extensively evaluated.
The aim of this study was to evaluate the combined effect of pequi oil (high in
unsaturated fatty acids) and incubation temperature on fermentation
characteristics and microbial communities using the rumen simulation technique. A
completely randomized experiment was conducted over a 28-day period using a
Rusitec system. The experiment was divided into four periods of 7 days each, the
first of which was a 7-day adaptation period followed by three experimental
periods. The two treatments consisted of a control diet (no pequi oil inclusion)
and a diet supplemented with pequi oil (1.5 mL/day) which increased the dietary
fat content to 6% (dry matter, DM-basis). Three fermenter vessels (i.e.,
replicates) were allocated to each treatment. In the first experimental period,
the incubation temperature was maintained at 39 degrees C, decreased to 35
degrees C in the second experimental period and then increased again to 39
degrees C in the third. Pequi oil was continuously supplemented during the
experiment. Microbial communities were assessed using high-throughput sequencing
of the archaeal and bacterial 16S rRNA gene. Methane production was reduced by
57% following a 4 degrees C decrease in incubation temperature. Supplementation
with pequi oil increased the dietary fat content to 6% (DM-basis) but did not
affect methane production. Analysis of the microbiota revealed that decreasing
incubation temperature to 35 degrees C affected the archaeal and bacterial
diversity and richness of liquid-associated microbes, but lipid supplementation
did not change microbial diversity.
PMID- 28702000
TI - Microbial Eukaryotes in an Arctic Under-Ice Spring Bloom North of Svalbard.
AB - Microbial eukaryotes can play prominent roles in the Arctic marine ecosystem, but
their diversity and variability is not well known in the ice-covered ecosystems.
We determined the community composition of microbial eukaryotes in an Arctic
under-ice spring bloom north of Svalbard using metabarcoding of DNA and RNA from
the hypervariable V4 region of 18S nrDNA. At the two stations studied, the
photosynthetic biomass was dominated by protists >3 MUm and was concentrated in
the upper 70-80 m, above the thermocline and halocline. Hierarchical cluster
analyses as well as ordination analyses showed a distinct clustering of the
microbial eukaryote communities according to a combination of water mass and
local environmental characteristics. While samples collected in the surface mixed
layer differed distinctly between the two sites, the deeper communities collected
in Atlantic Water were fairly similar despite being geographically distant. The
differentiation of the microbial eukaryote communities of the upper mixed water
was probably driven by local development and advection, while the lack of such
differentiation in the communities of Atlantic Water reflects the homogenizing
effect of water currents on microbial communities.
PMID- 28702001
TI - Metschnikowia pulcherrima Influences the Expression of Genes Involved in PDH
Bypass and Glyceropyruvic Fermentation in Saccharomyces cerevisiae.
AB - Previous studies reported that the use of Metschnikowia pulcherrima in sequential
culture fermentation with Saccharomyces cerevisiae mainly induced a reduction of
volatile acidity in wine. The impact of the presence of this yeast on the
metabolic pathway involved in pyruvate dehydrogenase (PDH) bypass and glycerol
production in S. cerevisiae has never been investigated. In this work, we
compared acetic acid and glycerol production kinetics between pure S. cerevisiae
culture and its sequential culture with M. pulcherrima during alcoholic
fermentation. In parallel, the expression levels of the principal genes involved
in PDH bypass and glyceropyruvic fermentation in S. cerevisiae were investigated.
A sequential culture of M. pulcherrima/S. cerevisiae at an inoculation ratio of
10:1 produced 40% less acetic acid than pure S. cerevisiae culture and led to the
enhancement of glycerol content (12% higher). High expression levels of pyruvate
decarboxylase PDC1 and PDC5, acetaldehyde dehydrogenase ALD6, alcohol
dehydrogenase ADH1 and glycerol-3-phosphate dehydrogenase PDC1 genes during the
first 3 days of fermentation in sequential culture conditions are highlighted.
Despite the complexity of correlating gene expression levels to acetic acid
formation kinetics, we demonstrate that the acetic acid production pathway is
altered by sequential culture conditions. Moreover, we show for the first time
that the entire acetic acid and glycerol metabolic pathway can be modulated in S.
cerevisiae by the presence of M. pulcherrima at the beginning of fermentation.
PMID- 28702002
TI - Production of Lipopeptide Biosurfactant by a Marine Nesterenkonia sp. and Its
Application in Food Industry.
AB - Biosurfactants are smart biomolecules which have wide spread application in
medicines, processed foods, cosmetics as well as in bioremediation. In food
industry, biosurfactants are used as emulsion stabilizing agents, antiadhesives,
and antimicrobial/antibiofilm agents. Nowadays biosurfactant demands in
industries has increased tremendously and therefore new bacterial strains are
being explored for large scale production of biosurfactants. In this study, an
actinobacterial strain MSA31 was isolated from a marine sponge Fasciospongia
cavernosa which showed high activity in biosurfactant screening assays such as
drop collapsing, oil displacement, lipase and emulsification. Lipopeptide
produced by MSA31 was found to be thermostable which was evident in differential
scanning calorimetry analysis. The spectral data obtained in the Fourier
transform infrared spectroscopy showed the presence of aliphatic groups combined
with peptide moiety which is a characteristic feature of lipopeptides. The
stability index of lipopeptide MSA31 revealed "halo-alkali and thermal tolerant
biosurfactant" which can be used in the food industry. Microtiter plate assay
showed 125 MUg/ml of lipopeptide was effective in reducing the biofilm formation
activity of pathogenic multidrug resistant Staphylococcus aureus. The confocal
laser scanning microscopic images provided further evidences that lipopeptide
MSA31 was an effective antibiofilm agent. The antioxidant activity of lipopeptide
MSA31 may be due to the presence of unsaturated fatty acid present in the
molecule. The brine shrimp cytotoxicity assay showed lipopeptide MSA31 was non
toxic and can be used as food additives. Incorporation of lipopeptide MSA31 in
muffin showed improved organoleptic qualities compared to positive and negative
control. This study provides a valuable input for this lipopeptide to be used in
food industry as an effective emulsifier, with good antioxidant activity and as a
protective agent against S. aureus.
PMID- 28702003
TI - Reduced Mass and Diversity of the Colonic Microbiome in Patients with Multiple
Sclerosis and Their Improvement with Ketogenic Diet.
AB - Background: Colonic microbiome is thought to be involved in auto-immune multiple
sclerosis (MS). Interactions between diet and the colonic microbiome in MS are
unknown. Methods: We compared the composition of the colonic microbiota
quantitatively in 25 MS patients and 14 healthy controls.Fluorescence in situ
hybridization (FISH) with 162 ribosomal RNA derived bacterial FISH probes was
used. Ten of the MS patients received a ketogenic diet for 6 months. Changes in
concentrations of 35 numerically substantial bacterial groups were monitored at
baseline and at 2, 12, and 23/24 weeks. Results: No MS typical microbiome pattern
was apparent.The total concentrations and diversity of substantial bacterial
groups were reduced in MS patients (P < 0.001). Bacterial groups detected with
EREC (mainly Roseburia), Bac303 (Bacteroides), and Fprau (Faecalibacterium
prausnitzii) probes were diminished the most. The individual changes were
multidirectional and inconsistent. The effects of a ketogenic diet were biphasic.
In the short term, bacterial concentrations and diversity were further reduced.
They started to recover at week 12 and exceeded significantly the baseline values
after 23-24 weeks on the ketogenic diet. Conclusions: Colonic biofermentative
function is markedly impaired in MS patients.The ketogenic diet normalized
concentrations of the colonic microbiome after 6 months.
PMID- 28702004
TI - Screening of the Antimicrobial Activity against Drug Resistant Bacteria of
Photorhabdus and Xenorhabdus Associated with Entomopathogenic Nematodes from Mae
Wong National Park, Thailand.
AB - Photorhabdus and Xenorhabdus are symbiotic with entomopathogenic nematodes (EPNs)
of the genera Heterorhabditis and Steinernema, respectively. These bacteria
produce several secondary metabolites including antimicrobial compounds. The
objectives of this study were to isolate and identify EPNs and their symbiotic
bacteria from Mae Wong National Park, Thailand and to evaluate the antibacterial
activities of symbiont extracts against drug resistant bacteria. A total of 550
soil samples from 110 sites were collected between August 2014 and July 2015. A
total of EPN isolates were obtained through baiting and White trap methods, which
yielded 21 Heterorhabditis and 3 Steinernema isolates. Based on molecular
identification and phylogenetic analysis, the most common species found in the
present study was P. luminescens subsp. akhurstii associated with H. indica.
Notably, two species of EPNs, H. zealandica and S. kushidai, and two species of
symbiotic bacteria, X. japonica and P. temperata subsp. temperata represented new
recorded organisms in Thailand. Furthermore, the association between P. temperata
subsp. temperata and H. zealandica has not previously been reported worldwide.
Disk diffusion, minimal inhibitory concentration, and minimal bactericidal
concentration analyses demonstrated that the crude compound extracted by ethyl
acetate from P. temperata subsp. temperata could inhibit the growth of up to 10
strains of drug resistant bacteria. Based on HPLC-MS analysis, compound classes
in bacterial extracts were identified as GameXPeptide, xenoamicin, xenocoumacin,
mevalagmapeptide phurealipids derivatives, and isopropylstilbene. Together, the
results of this study provide evidence for the diversity of EPNs and their
symbiotic bacteria in Mae Wong National Park, Thailand and demonstrate their
novel associations. These findings also provide an important foundation for
further research regarding the antimicrobial activity of Photorhabdus bacteria.
PMID- 28702005
TI - Insights into a Novel blaKPC-2-Encoding IncP-6 Plasmid Reveal Carbapenem
Resistance Circulation in Several Enterobacteriaceae Species from Wastewater and
a Hospital Source in Spain.
AB - Untreated wastewater, particularly from hospitals and other healthcare
facilities, is considered to be a reservoir for multidrug-resistant bacteria.
However, its role in the spread of antibiotic resistances in the human population
remains poorly investigated. We used whole genome sequencing to analyze 25 KPC-2
producing Enterobacteriaceae isolates from sewage water collected during a 3-year
period and three clinical Citrobacter freundii isolates from a tertiary hospital
in the same collection area in Spain. We detected a common, recently described,
IncP-6 plasmid carrying the gene blaKPC-2 in 21 isolates from both sources. The
plasmid was present in diverse environmental bacterial species of opportunistic
pathogens such as C. freundii, Enterobacter cloacae, Klebsiella oxytoca, and
Raoultella ornithinolytica. The 40,186 bp IncP-6 plasmid encoded 52 coding
sequences and was composed of three uniquely combined regions that were derived
from other plasmids recently reported in different countries of South America.
The region harboring the carbapenem resistance gene (14 kb) contained a Tn3
transposon disrupted by an ISApu-flanked element and the core sequence composed
by ISKpn6/blaKPC-2/DeltablaTEM-1/ISKpn27. We document here the presence of a
novel promiscuous blaKPC-2 plasmid circulating in environmental bacteria in
wastewater and human populations.
PMID- 28702006
TI - The Conserved Actinobacterial Two-Component System MtrAB Coordinates
Chloramphenicol Production with Sporulation in Streptomyces venezuelae NRRL B
65442.
AB - Streptomyces bacteria make numerous secondary metabolites, including half of all
known antibiotics. Production of antibiotics is usually coordinated with the
onset of sporulation but the cross regulation of these processes is not fully
understood. This is important because most Streptomyces antibiotics are produced
at low levels or not at all under laboratory conditions and this makes large
scale production of these compounds very challenging. Here, we characterize the
highly conserved actinobacterial two-component system MtrAB in the model organism
Streptomyces venezuelae and provide evidence that it coordinates production of
the antibiotic chloramphenicol with sporulation. MtrAB are known to coordinate
DNA replication and cell division in Mycobacterium tuberculosis where TB-MtrA is
essential for viability but MtrB is dispensable. We deleted mtrB in S. venezuelae
and this resulted in a global shift in the metabolome, including constitutive,
higher-level production of chloramphenicol. We found that chloramphenicol is
detectable in the wild-type strain, but only at very low levels and only after it
has sporulated. ChIP-seq showed that MtrA binds upstream of DNA replication and
cell division genes and genes required for chloramphenicol production. dnaA,
dnaN, oriC, and wblE (whiB1) are DNA binding targets for MtrA in both M.
tuberculosis and S. venezuelae. Intriguingly, over-expression of TB-MtrA and gain
of function TB- and Sv-MtrA proteins in S. venezuelae also switched on higher
level production of chloramphenicol. Given the conservation of MtrAB, these
constructs might be useful tools for manipulating antibiotic production in other
filamentous actinomycetes.
PMID- 28702007
TI - Identification, Bioactivity, and Productivity of Actinomycins from the Marine
Derived Streptomyces heliomycini.
AB - In the process of profiling the secondary metabolites of actinobacteria isolated
from the Saudi coastal habitats for production of antibiotics and anti-cancer
drugs, the cultures of strain WH1 that was identified as Streptomyces heliomycini
exhibited strong antibacterial activity against Staphylococcus aureus. By means
of MS and NMR techniques, the active compounds were characterized as actinomycins
X0beta, X2, and D, respectively. The research on the productivity of this strain
for actinomycins revealed that the highest production of actinomycins X0beta, X2,
and D was reached in the medium MII within 5% salinity and pH 8.5. In this
optimized condition, the fermentation titers of actinomycins X0beta, X2, and D
were 107.6 +/- 4.2, 283.4 +/- 75.3, and 458.0 +/- 76.3 mg/L, respectively. All
the three actinomycins X0beta, X2, and D showed potent cytotoxicities against the
MCF-7, K562, and A549 tumor cell lines, in which actinomycin X2 was the most
active against the three tumor cell lines with the IC50 values of 0.8-1.8 nM.
Both actinomycins X2 and D showed potent antibacterial activities against S.
aureus and the methicillin-resistant S. aureus, Bacillus subtilis, and B. cereus
and the actinomycin X2 was more potent.
PMID- 28702008
TI - Hypersensitive Response of Plasmid-Encoded AHL Synthase Gene to Lifestyle and
Nutrient by Ensifer adhaerens X097.
AB - It is known that some bacteria, especially members of the family Rhizobiaceae,
have multiple N-acyl homoserine lactones (AHL) synthase genes and produce
multiple AHL signals. However, how bacteria selectively utilize these multiple
genes and signals to cope with changing environments is poorly understood.
Ensifer adhaerens is an important microorganism in terms of biotechnology,
ecology and evolutionary. In this study, we investigated the AHL-based QS system
of E. adhaerens X097 and its response to different lifestyles or nutrients. Draft
genome sequence data indicated that X097 harbored three distinct AHL synthase
genes (ensI1, 2, 3) and seven luxR homologs, which was different from other E.
adhaerens strains. In vitro expression indicated that plasmid-encoded ensI1 and
ensI2 directed production of multiple AHLs, while chromosome-encoded ensI3 only
directed production of C14-HSL. Predicted three dimensional structure of EnsI3
was quite different from that of EnsI1 and EnsI2. X097 produced different AHL
profiles in Luria-Bertani (LB) and NFB medium, under biofilm and planktonic
lifestyle, respectively. Notably, expression of ensI1 and ensI2 but not ensI3 is
hypersensitive to different lifestyles and nutrients. The hypersensitive response
of plasmid-encoded AHL synthase genes to different culture conditions may shed a
light on the phylogenetic development of AHL synthase genes in Rhizobiaceae
family.
PMID- 28702009
TI - CRM1 Inhibitors for Antiviral Therapy.
AB - Infectious diseases are a major global concern and despite major advancements in
medical research, still cause significant morbidity and mortality. Progress in
antiviral therapy is particularly hindered by appearance of mutants capable of
overcoming the effects of drugs targeting viral components. Alternatively,
development of drugs targeting host proteins essential for completion of viral
lifecycle holds potential as a viable strategy for antiviral therapy.
Nucleocytoplasmic trafficking pathways in particular are involved in several
pathological conditions including cancer and viral infections, where hijacking or
alteration of function of key transporter proteins, such as Chromosome Region
Maintenance1 (CRM1) is observed. Overexpression of CRM1-mediated nuclear export
is evident in several solid and hematological malignancies. Interestingly, CRM1
mediated nuclear export of viral components is crucial in various stages of the
viral lifecycle and assembly. This review summarizes the role of CRM1 in cancer
and selected viruses. Leptomycin B (LMB) is the prototypical inhibitor of CRM1
potent against various cancer cell lines overexpressing CRM1 and in limiting
viral infections at nanomolar concentrations in vitro. However, the irreversible
shutdown of nuclear export results in high cytotoxicity and limited efficacy in
vivo. This has prompted search for synthetic and natural CRM1 inhibitors that can
potentially be developed as broadly active antivirals, some of which are
summarized in this review.
PMID- 28702010
TI - Comparison among the Quantification of Bacterial Pathogens by qPCR, dPCR, and
Cultural Methods.
AB - The demand for rapid methods for the quantification of pathogens is increasing.
Among these methods, those based on nucleic acids amplification (quantitative
PCRs) are the most widespread worldwide. Together with the qPCR, a new approach
named digital PCR (dPCR), has rapidly gained importance. The aim of our study was
to compare the results obtained using two different dPCR systems and one qPCR in
the quantification of three different bacterial pathogens: Listeria
monocytogenes, Francisella tularensis, and Mycobacterium avium subsp.
paratuberculosis. For this purpose, three pre-existing qPCRs were used, while the
same primers and probes, as well as PCR conditions, were transferred to two
different dPCR systems: the QX200 (Bio-Rad) and the Quant Studio 3D (Applied
Biosystems). The limits of detection and limits of quantification for all
pathogens, and all PCR approaches applied, were determined using genomic pure
DNAs. The quantification of unknown decimal suspensions of the three bacteria
obtained by the three different PCR approaches was compared through the Linear
Regression and Bland and Altman analyses. Our results suggest that, both dPCRs
are able to quantify the same amount of bacteria, while the comparison among
dPCRs and qPCRs, showed both over and under-estimation of the bacteria present in
the unknown suspensions. Our results showed qPCR over-estimated the amount of M.
avium subsp. paratuberculosis and F. tularensis cells. On the contrary, qPCR,
compared to QX200 dPCR, under-estimated the amount of L. monocytogenes cells.
However, the maximum difference among PCRs approaches was <0.5 Log10, while
cultural methods underestimated the number of bacteria by one to two Log10 for
Francisella tularensis and Mycobacterium avium subsp. paratuberculosis. On the
other hand, cultural and PCRs methods quantified the same amount of bacteria for
L. monocytogenes, suggesting for this last pathogen, PCRs approaches can be
considered as a valid alternative to the cultural ones.
PMID- 28702011
TI - Bridging the Gap to Non-toxic Fungal Control: Lupinus-Derived Blad-Containing
Oligomer as a Novel Candidate to Combat Human Pathogenic Fungi.
AB - The lack of antifungal drugs with novel modes of action reaching the clinic is a
serious concern. Recently a novel antifungal protein referred to as Blad
containing oligomer (BCO) has received regulatory approval as an agricultural
antifungal agent. Interestingly its spectrum of antifungal activity includes
human pathogens such as Candida albicans, however, its mode of action has yet to
be elucidated. Here we demonstrate that BCO exerts its antifungal activity
through inhibition of metal ion homeostasis which results in apoptotic cell death
in C. albicans. HIP HOP profiling in Saccharomyces cerevisiae using a panel of
signature strains that are characteristic for common modes of action identified
hypersensitivity in yeast lacking the iron-dependent transcription factor Aft1
suggesting restricted iron uptake as a mode of action. Furthermore, global
transcriptome profiling in C. albicans also identified disruption of metal ion
homeostasis as a potential mode of action. Experiments were carried out to assess
the effect of divalent metal ions on the antifungal activity of BCO revealing
that BCO activity is antagonized by metal ions such as Mn2+, Zn2+, and Fe2+. The
transcriptome profile also implicated sterol synthesis as a possible secondary
mode of action which was subsequently confirmed in sterol synthesis assays in C.
albicans. Animal models for toxicity showed that BCO is generally well tolerated
and presents a promising safety profile as a topical applied agent. Given its
potent broad spectrum antifungal activity and novel multitarget mode of action,
we propose BCO as a promising new antifungal agent for the topical treatment of
fungal infections.
PMID- 28702012
TI - Community Composition of Nitrous Oxide Consuming Bacteria in the Oxygen Minimum
Zone of the Eastern Tropical South Pacific.
AB - The ozone-depleting and greenhouse gas, nitrous oxide (N2O), is mainly consumed
by the microbially mediated anaerobic process, denitrification. N2O consumption
is the last step in canonical denitrification, and is also the least O2 tolerant
step. Community composition of total and active N2O consuming bacteria was
analyzed based on total (DNA) and transcriptionally active (RNA) nitrous oxide
reductase (nosZ) genes using a functional gene microarray. The total and active
nosZ communities were dominated by a limited number of nosZ archetypes,
affiliated with bacteria from marine, soil and marsh environments. In addition to
nosZ genes related to those of known marine denitrifiers, atypical nosZ genes,
related to those of soil bacteria that do not possess a complete denitrification
pathway, were also detected, especially in surface waters. The community
composition of the total nosZ assemblage was significantly different from the
active assemblage. The community composition of the total nosZ assemblage was
significantly different between coastal and off-shore stations. The low oxygen
assemblages from both stations were similar to each other, while the higher
oxygen assemblages were more variable. Community composition of the active nosZ
assemblage was also significantly different between stations, and varied with N2O
concentration but not O2. Notably, nosZ assemblages were not only present but
also active in oxygenated seawater: the abundance of total and active nosZ
bacteria from oxygenated surface water (indicated by nosZ gene copy number) was
similar to or even larger than in anoxic waters, implying the potential for N2O
consumption even in the oxygenated surface water.
PMID- 28702013
TI - Nitrogen Fixation Aligns with nifH Abundance and Expression in Two Coral Trophic
Functional Groups.
AB - Microbial nitrogen fixation (diazotrophy) is a functional trait widely associated
with tropical reef-building (scleractinian) corals. While the integral role of
nitrogen fixation in coral nutrient dynamics is recognized, its ecological
significance across different coral functional groups remains yet to be
evaluated. Here we set out to compare molecular and physiological patterns of
diazotrophy (i.e., nifH gene abundance and expression as well as nitrogen
fixation rates) in two coral families with contrasting trophic strategies: highly
heterotrophic, free-living members of the family Fungiidae (Pleuractis granulosa,
Ctenactis echinata), and mostly autotrophic coral holobionts with low
heterotrophic capacity (Pocilloporidae: Pocillopora verrucosa, Stylophora
pistillata). The Fungiidae exhibited low diazotroph abundance (based on nifH gene
copy numbers) and activity (based on nifH gene expression and the absence of
detectable nitrogen fixation rates). In contrast, the mostly autotrophic
Pocilloporidae exhibited nifH gene copy numbers and gene expression two orders of
magnitude higher than in the Fungiidae, which coincided with detectable nitrogen
fixation activity. Based on these data, we suggest that nitrogen fixation
compensates for the low heterotrophic nitrogen uptake in autotrophic corals.
Consequently, the ecological importance of diazotrophy in coral holobionts may be
determined by the trophic functional group of the host.
PMID- 28702014
TI - Detecting the Diversity of Mycoplasma and Ureaplasma Endosymbionts Hosted by
Trichomonas vaginalis Isolates.
AB - Objectives: The symbiosis of Trichomonas vaginalis and Mycoplasma hominis is the
first described association between two obligate human parasites. Trichomonas is
the niche and the vector for the transmission of M. hominis infection. This
clinically significant symbiosis may affect T. vaginalis virulence and
susceptibility to treatment. The aims of this study were to investigate the
intracellularly present Mycoplasma and Ureaplasma species in T. vaginalis strains
isolated from the vaginal discharge of infected women as well as to trace the
diversity pattern among the species detected in the isolated strains. Methods:
Hundred pure T. vaginalis cultures were isolated from ~7,500 patient specimens
presented with clinical purulent vaginitis. PCR and sequencing for
Mycoplasma/Ureaplasma spp. were performed in DNA extracted from the pure
cultures. In addition, vaginal discharge samples were cultured for the presence
of M. hominis and U. urealyticum. Phylogenetic analysis assisted the
identification of interspecies relationships between the Mycoplasma and
Ureaplasma isolates. Results: Fifty four percentage of T. vaginalis isolates were
harboring Mycoplasma spp. Phylogenetic analysis revealed three distinct clusters,
two with already characterized M. hominis and Ureaplasma spp. (37% of total
Mycoplasma spp.), whereas one group formed a distinct cluster matched with the
newly identified species Candidatus Mycoplasma girerdii (59.3%) and one or more
unknown Mycoplasma spp. (3.7%). Conclusions:T. vaginalis strains associated with
vaginal infection might host intracellular mycoplasmas or ureaplasmas.
Intracellular Mollicutes that remain undetected in the extracellular environment
when conventional diagnostic methods are implemented may comprise either novel
species, such as Candidatus M. giredii, or unknown species with yet unexplored
clinical significance.
PMID- 28702015
TI - Inhibition of the Rumen Ciliate Entodinium caudatum by Antibiotics.
AB - Axenic cultures of free-living aerobic ciliates, such as Tetrahymena thermophila
and Paramecium aurelia, have been established and routinely used in laboratory
research, greatly facilitating, or enabling characterization of their metabolism,
physiology, and ecology. Ruminal protozoa are anaerobic ciliates, and they play
important roles in feed digestion and fermentation. Although, repeatedly
attempted, no laboratory-maintainable axenic culture of ruminal ciliates has been
established. When axenic ciliate cultures are developed, antibiotics are required
to eliminate the accompanying bacteria. Ruminal ciliates gradually lose viability
upon antibiotic treatments, and the resultant axenic cultures can only last for
short periods of time. The objective of this study was to evaluate eight
antibiotics that have been evaluated in developing axenic cultures of ruminal
ciliates, for their toxicity to Entodinium caudatum, which is the most
predominant ruminal ciliate species. Scanning and transmission electron
microscopy (TEM) showed that the antibiotics damaged both the cell surface and
nuclei of E. caudatum and increased accumulation of intracellular glycogen.
Combinations of the three least toxic antibiotics failed to eliminate the
bacteria that are present in the E. caudatum culture. The combination of
ampicillin, carbenicillin, streptomycin, and oxytetracycline was able to
eliminate all the bacteria, but the resultant axenic E. caudatum culture
gradually lost viability. Adding the bacterial fraction (live) separated from an
untreated E. caudatum culture reversed the viability decline and recovered the
growth of the treated E. caudatum culture, whereas feeding nine strains of live
bacteria isolated from E. caudatum cells, either individually or in combination,
could not. Nutritional and metabolic dependence on its associated bacteria,
accompanied with direct and indirect inhibition by antibiotics, makes it
difficult to establish an axenic culture of E. caudatum. Monoxenic or polyxenic
cultures of E. caudatum could be developed if the essential symbiotic partner(s)
can be identified.
PMID- 28702016
TI - Burn Serum Increases Staphylococcus aureus Biofilm Formation via Oxidative
Stress.
AB - Staphylococcus aureus is a common pathogen isolated from burn patients that can
form biofilms on burn wounds and implanted deep vein catheters, which often leads
to refractory infections or even biofilm-related sepsis. As biofilm formation is
usually regulated by environmental conditions, we hypothesized that serum
composition may be altered after burn injury, potentially affecting the ability
of infecting bacteria to form biofilms. As predicted, we observed that serum from
burn-injured rats increases biofilm formation by S. aureus and also induces
bacterial aggregation and adherence to human fibronectin and fibrinogen. Analysis
of potential regulatory factors revealed that exposure to burn serum decreases
expression of the quorum-sensing agr system and increases mRNA levels of some
biofilm inducers such as sarA and icaA. In addition, we also observed that burn
serum imposes oxidative stress and increases expression of key oxidoreductase
genes (sodA, sodM, katA, and ahpC) in S. aureus. Importantly, the ability of burn
serum to enhance biofilm formation and bacterial cell aggregation can be
abrogated by treatment with an antioxidant. Taken together, these findings
indicate that burn serum increases S. aureus biofilm formation via elevated
oxidative stress, and may lead to novel strategies to control biofilm formation
and infection in burn patients.
PMID- 28702017
TI - Acetic Acid Causes Endoplasmic Reticulum Stress and Induces the Unfolded Protein
Response in Saccharomyces cerevisiae.
AB - Since acetic acid inhibits the growth and fermentation ability of Saccharomyces
cerevisiae, it is one of the practical hindrances to the efficient production of
bioethanol from a lignocellulosic biomass. Although extensive information is
available on yeast response to acetic acid stress, the involvement of endoplasmic
reticulum (ER) and unfolded protein response (UPR) has not been addressed. We
herein demonstrated that acetic acid causes ER stress and induces the UPR. The
accumulation of misfolded proteins in the ER and activation of Ire1p and Hac1p,
an ER-stress sensor and ER stress-responsive transcription factor, respectively,
were induced by a treatment with acetic acid stress (>0.2% v/v). Other
monocarboxylic acids such as propionic acid and sorbic acid, but not lactic acid,
also induced the UPR. Additionally, ire1Delta and hac1Delta cells were more
sensitive to acetic acid than wild-type cells, indicating that activation of the
Ire1p-Hac1p pathway is required for maximum tolerance to acetic acid.
Furthermore, the combination of mild acetic acid stress (0.1% acetic acid) and
mild ethanol stress (5% ethanol) induced the UPR, whereas neither mild ethanol
stress nor mild acetic acid stress individually activated Ire1p, suggesting that
ER stress is easily induced in yeast cells during the fermentation process of
lignocellulosic hydrolysates. It was possible to avoid the induction of ER stress
caused by acetic acid and the combined stress by adjusting extracellular pH.
PMID- 28702018
TI - A Mutant Isoform of ObgE Causes Cell Death by Interfering with Cell Division.
AB - Cell division is a vital part of the cell cycle that is fundamental to all life.
Despite decades of intense investigation, this process is still incompletely
understood. Previously, the essential GTPase ObgE, which plays a role in a myriad
of basic cellular processes (such as initiation of DNA replication, chromosome
segregation, and ribosome assembly), was proposed to act as a cell cycle
checkpoint in Escherichia coli by licensing chromosome segregation. We here
describe the effect of a mutant isoform of ObgE (ObgE*) that causes cell death by
irreversible arrest of the cell cycle at the stage of cell division. Notably,
chromosome segregation is allowed to proceed normally in the presence of ObgE*,
after which cell division is blocked. Under conditions of rapid growth, ongoing
cell cycles are completed before cell cycle arrest by ObgE* becomes effective.
However, cell division defects caused by ObgE* then elicit lysis through
formation of membrane blebs at aberrant division sites. Based on our results, and
because ObgE was previously implicated in cell cycle regulation, we hypothesize
that the mutation in ObgE* disrupts the normal role of ObgE in cell division. We
discuss how ObgE* could reveal more about the intricate role of wild-type ObgE in
division and cell cycle control. Moreover, since Obg is widely conserved and
essential for viability, also in eukaryotes, our findings might be applicable to
other organisms as well.
PMID- 28702019
TI - Functional Resilience and Response to a Dietary Additive (Kefir) in Models of
Foregut and Hindgut Microbial Fermentation In Vitro.
AB - Stability in gut ecosystems is an important area of study that impacts on the use
of additives and is related with several pathologies. Kefir is a fermented milk
drink made with a consortium of yeast and bacteria as a fermentation starter, of
which the use as additive in companion and livestock animals has increased in the
last few years. To investigate the effect of kefir milk on foregut and hindgut
digestive systems, an in vitro approach was followed. Either rumen fluid or horse
fecal contents were used as a microbial inoculate and the inclusion of kefir
(fresh, autoclaved, or pasteurized) was tested. Gas production over 72 h of
incubation was recorded and pH, volatile fatty acids (VFAs), lactate and ammonia
concentration as well as lactic acid (LAB) and acetic acid bacteria, and yeast
total numbers were also measured. Both direct and indirect (by subtracting their
respective blanks) effects were analyzed and a multivariate analysis was
performed to compare foregut and hindgut fermentation models. Addition of kefir
boosted the fermentation by increasing molar concentration of VFAs and ammonia
and shifting the Acetate to Propionate ratio in both models but heat processing
techniques like pasteurization or autoclaving influenced the way the kefir is
fermented and reacts with the present microbiota. In terms of comparison between
both models, the foregut model seems to be less affected by the inclusion of
Kefir than the hindgut model. In terms of variability in the response, the
hindgut model appeared to be more variable than the foregut model in the way that
it reacted indirectly to the addition of different types of kefir.
PMID- 28702020
TI - Repetitive Short-Term Stimuli Imposed in Poor Mixing Zones Induce Long-Term
Adaptation of E. coli Cultures in Large-Scale Bioreactors: Experimental Evidence
and Mathematical Model.
AB - Rapidly changing concentrations of substrates frequently occur during large-scale
microbial cultivations. These changing conditions, caused by large mixing times,
result in a heterogeneous population distribution. Here, we present a powerful
and efficient modeling approach to predict the influence of varying substrate
levels on the transcriptional and translational response of the cell. This
approach consists of two parts, a single-cell model to describe transcription and
translation for an exemplary operon (trp operon) and a second part to
characterize cell distribution during the experimental setup. Combination of both
models enables prediction of transcriptional patterns for the whole population.
In summary, the resulting model is not only able to anticipate the experimentally
observed short-term and long-term transcriptional response, it further allows
envision of altered protein levels. Our model shows that locally induced stress
responses propagate throughout the bioreactor, resulting in temporal, and spatial
population heterogeneity. Stress induced transcriptional response leads to a new
population steady-state shortly after imposing fluctuating substrate conditions.
In contrast, the protein levels take more than 10 h to achieve steady-state
conditions.
PMID- 28702021
TI - Combination of Metabolomic and Proteomic Analysis Revealed Different Features
among Lactobacillus delbrueckii Subspecies bulgaricus and lactis Strains While In
Vivo Testing in the Model Organism Caenorhabditis elegans Highlighted Probiotic
Properties.
AB - Lactobacillus delbrueckii represents a technologically relevant member of lactic
acid bacteria, since the two subspecies bulgaricus and lactis are widely
associated with fermented dairy products. In the present work, we report the
characterization of two commercial strains belonging to L. delbrueckii subspecies
bulgaricus, lactis and a novel strain previously isolated from a traditional
fermented fresh cheese. A phenomic approach was performed by combining
metabolomic and proteomic analysis of the three strains, which were subsequently
supplemented as food source to the model organism Caenorhabditis elegans, with
the final aim to evaluate their possible probiotic effects. Restriction analysis
of 16S ribosomal DNA revealed that the novel foodborne strain belonged to L.
delbrueckii subspecies lactis. Proteomic and metabolomic approaches showed
differences in folate, aminoacid and sugar metabolic pathways among the three
strains. Moreover, evaluation of C. elegans lifespan, larval development, brood
size, and bacterial colonization capacity demonstrated that L. delbrueckii subsp.
bulgaricus diet exerted beneficial effects on nematodes. On the other hand, both
L. delbrueckii subsp. lactis strains affected lifespan and larval development. We
have characterized three strains belonging to L. delbrueckii subspecies
bulgaricus and lactis highlighting their divergent origin. In particular, the two
closely related isolates L. delbrueckii subspecies lactis display different
galactose metabolic capabilities. Moreover, the L. delbrueckii subspecies
bulgaricus strain demonstrated potential probiotic features. Combination of omic
platforms coupled with in vivo screening in the simple model organism C. elegans
is a powerful tool to characterize industrially relevant bacterial isolates.
PMID- 28702022
TI - Preparing the Gut with Antibiotics Enhances Gut Microbiota Reprogramming
Efficiency by Promoting Xenomicrobiota Colonization.
AB - Gut microbiota plays multiple important roles in intestinal and physiological
homeostasis, and using fecal microbiota transplantation (FMT) to reprogram gut
microbiota has demonstrated promise for redressing intestinal and physiological
disorders. This study tested the alterations in reprogramming efficiency caused
by different gut preparation procedures and explored the associated underlying
mechanisms. We prepared the guts of mice for FMT by administering one of the
three most-clinically used pretreatments [antibiotics, bowel cleansing (BC)
solution, or no pretreatment], and we found that preparing the gut with
antibiotics induced a more efficient modification of the gut bacterial community
than was induced by either of the other two pretreatment types. The increased
efficiency of antibiotic treatment appeared to occur via increasing the
xenomicrobiota colonization. Further analysis demonstrated that antibiotic
treatment of mice induced intestinal microbiota disruption, mostly by expelling
antibiotic-sensitive bacteria, while the indigenous microbiota was maintained
after treatment with a BC solution or in the absence of pretreatment. The amount
of antibiotic-resistant bacteria increased shortly after antibiotics usage but
subsequently decreased after FMT administration. Together, these results suggest
that FMT relied on the available niches in the intestinal mucosa and that
preparing the gut with antibiotics facilitated xenomicrobiota colonization in the
intestinal mucosa, which thus enhanced the overall gut microbiota reprogramming
efficiency.
PMID- 28702023
TI - Host Resistance and Temperature-Dependent Evolution of Aggressiveness in the
Plant Pathogen Zymoseptoria tritici.
AB - Understanding how habitat heterogeneity may affect the evolution of plant
pathogens is essential to effectively predict new epidemiological landscapes and
manage genetic diversity under changing global climatic conditions. In this
study, we explore the effects of habitat heterogeneity, as determined by
variation in host resistance and local temperature, on the evolution of
Zymoseptoria tritici by comparing the aggressiveness development of five Z.
tritici populations originated from different parts of the world on two wheat
cultivars varying in resistance to the pathogen. Our results show that host
resistance plays an important role in the evolution of Z. tritici. The pathogen
was under weak, constraining selection on a host with quantitative resistance but
under a stronger, directional selection on a susceptible host. This difference is
consistent with theoretical expectations that suggest that quantitative
resistance may slow down the evolution of pathogens and therefore be more
durable. Our results also show that local temperature interacts with host
resistance in influencing the evolution of the pathogen. When infecting a
susceptible host, aggressiveness development of Z. tritici was negatively
correlated to temperatures of the original collection sites, suggesting a trade
off between the pathogen's abilities of adapting to higher temperature and
causing disease and global warming may have a negative effect on the evolution of
pathogens. The finding that no such relationship was detected when the pathogen
infected the partially resistant cultivars indicates the evolution of pathogens
in quantitatively resistant hosts is less influenced by environments than in
susceptible hosts.
PMID- 28702024
TI - Full Length Interleukin 33 Aggravates Radiation-Induced Skin Reaction.
AB - The interleukin (IL)-1 family member IL-33 has been described as intracellular
alarmin with broad roles in wound healing, skin inflammation but also
autoimmunity. Its dichotomy between full length (fl) IL-33 and the mature (m)
form of IL-33 and its release by necrosis is still not fully understood. Here, we
compare functional consequences of both forms in the skin in vivo, and therefore
generated two lines of transgenic mice which selectively overexpress mmIL-33 and
flmIL-33 in basal keratinocytes. Transgene mRNA was expressed at high level in
skin of both lines but not in organs due to the specific K14 promoter. We could
demonstrate that transgenic overexpression of mmIL-33 in murine keratinocytes
leads to a spontaneous skin inflammation as opposed to flmIL-33. K14-mmIL-33 mice
synthesize and secrete high amounts of mmIL-33 along with massive cutaneous
manifestations, like increased epidermis and dermis thickness, infiltration of
mast cells in the epidermis and dermis layers and marked hyperkeratosis. Using
skin inflammation models such as IL-23 administration, imiquimod treatment, or
mechanical irritation did not lead to exacerbated inflammation in the K14-flmIL
33 strain. As radiation induces a strong dermatitis due to apoptosis and
necrosis, we determined the effect of fractionated radiation (12 Gy, 4 times). In
comparison to wild-type mice, an increase in ear thickness in flmIL-33 transgenic
mice was observed 25 days after irradiation. Macroscopic examination showed more
severe skin symptoms in irradiated ears compared to controls. In summary,
secreted mmIL-33 itself has a potent capacity in skin inflammation whereas fl IL
33 is limited due to its intracellular retention. During tissue damage, fl IL-33
exacerbated radiation-induced skin reaction.
PMID- 28702026
TI - Lessons from Genetic Studies of Primary Immunodeficiencies in a Highly
Consanguineous Population.
AB - During the last decades, the study of primary immunodeficiencies (PIDs) has
contributed tremendously to unravel novel pathways involved in a variety of
immune responses. Many of these PIDs have an autosomal recessive (AR) mode of
inheritance. Thus, the investigation of the molecular basis of PIDs is
particularly relevant in consanguineous populations from Middle East and North
Africa (MENA). Although significant efforts have been made in recent years to
develop genetic testing across the MENA region, few comprehensive studies
reporting molecular basis of PIDs in these settings are available. Herein, we
review genetic characteristics of PIDs identified in 168 patients from an inbred
Tunisian population. A spectrum of 25 genes involved was analyzed. We show that
AR forms compared to X-linked or autosomal dominant forms are clearly the most
frequent. Furthermore, the study of informative consanguineous families did allow
the identification of a novel hyper-IgE syndrome linked to phosphoglucomutase 3
mutations. We did also report a novel form of autoimmune lymphoproliferative
syndrome caused by homozygous FAS mutations with normal or residual protein
expression as well as a novel AR transcription factor 3 deficiency. Finally, we
identified several founder effects for specific AR mutations. This did facilitate
the implementation of preventive approaches through genetic counseling in
affected consanguineous families. All together, these findings highlight the
specific nature of highly consanguineous populations and confirm the importance
of unraveling the molecular basis of genetic diseases in this context. Besides
providing a better fundamental knowledge of novel pathways, their study is
improving diagnosis strategies and appropriate care.
PMID- 28702025
TI - Cellular and Molecular Defects Underlying Invasive Fungal Infections-Revelations
from Endemic Mycoses.
AB - The global burden of fungal diseases has been increasing, as a result of the
expanding number of susceptible individuals including people living with human
immunodeficiency virus (HIV), hematopoietic stem cell or organ transplant
recipients, patients with malignancies or immunological conditions receiving
immunosuppressive treatment, premature neonates, and the elderly. Opportunistic
fungal pathogens such as Aspergillus, Candida, Cryptococcus, Rhizopus, and
Pneumocystis jiroveci are distributed worldwide and constitute the majority of
invasive fungal infections (IFIs). Dimorphic fungi such as Histoplasma
capsulatum, Coccidioides spp., Paracoccidioides spp., Blastomyces dermatiditis,
Sporothrix schenckii, Talaromyces (Penicillium) marneffei, and Emmonsia spp. are
geographically restricted to their respective habitats and cause endemic mycoses.
Disseminated histoplasmosis, coccidioidomycosis, and T. marneffei infection are
recognized as acquired immunodeficiency syndrome (AIDS)-defining conditions,
while the rest also cause high rate of morbidities and mortalities in patients
with HIV infection and other immunocompromised conditions. In the past decade, a
growing number of monogenic immunodeficiency disorders causing increased
susceptibility to fungal infections have been discovered. In particular, defects
of the IL-12/IFN-gamma pathway and T-helper 17-mediated response are associated
with increased susceptibility to endemic mycoses. In this review, we put together
the various forms of endemic mycoses on the map and take a journey around the
world to examine how cellular and molecular defects of the immune system
predispose to invasive endemic fungal infections, including primary
immunodeficiencies, individuals with autoantibodies against interferon-gamma, and
those receiving biologic response modifiers. Though rare, these conditions
provide importance insights to host defense mechanisms against endemic fungi,
which can only be appreciated in unique climatic and geographical regions.
PMID- 28702027
TI - Decreased Human Leukocyte Antigen-G Expression by miR-133a Contributes to
Impairment of Proinvasion and Proangiogenesis Functions of Decidual NK Cells.
AB - Human leukocyte antigen (HLA)-G plays a crucial role in conferring fetal-maternal
tolerance and ensuring a successful pregnancy. CD56bright natural killer (NK)
cells accumulate at the maternal decidua in large numbers during pregnancy and
are found in direct contact with fetal trophoblasts. There are increasing
evidences that decidual NK (dNK) cells are crucial for pregnancy. However, the
regulation of dNK cells is mostly unknown. Here, we provide evidences that the
secretion function of dNK cells in recurrent spontaneous abortion was impaired,
which led to the impairment of the proinvasion and proangiogenesis functions of
dNK cells. Decreased HLA-G expression induced by the transfection of miR-133a
mimics in HTR-8/SVneo affected the secretory functions of dNK cells. Thus, our
data revealed that the functions of dNK cells could be suppressed by the
decreased expression of HLA-G and suggest a possible mechanism of recurrent
miscarriage.
PMID- 28702028
TI - Immunization with the Malaria Diversity-Covering Blood-Stage Vaccine Candidate
Plasmodium falciparum Apical Membrane Antigen 1 DiCo in Complex with Its Natural
Ligand PfRon2 Does Not Improve the In Vitro Efficacy.
AB - The blood-stage malaria vaccine candidate Plasmodium falciparum apical membrane
antigen 1 (PfAMA1) can induce strong parasite growth-inhibitory antibody
responses in animals but has not achieved the anticipated efficacy in clinical
trials. Possible explanations in humans are the insufficient potency of the
elicited antibody responses, as well as the high degree of sequence polymorphisms
found in the field. Several strategies have been developed to improve the cross
strain coverage of PfAMA1-based vaccines, whereas innovative concepts to increase
the potency of PfAMA1-specific IgG responses have received little attention even
though this may be an essential requirement for protective efficacy. A previous
study has demonstrated that immunization with a complex of PyAMA1 and PyRON2, a
ligand with an essential functional role in erythrocyte invasion, leads to
protection from lethal Plasmodium yoelli challenge in an animal model and
suggested to extend this strategy toward improved strain coverage by using
multiple PfAMA1 alleles in combination with PfRon2L. As an alternative approach
along this line, we decided to use PfRon2L in combination with three PfAMA1
diversity covering variants (DiCo) to investigate the potential of this complex
to induce more potent parasite growth inhibitory immune response in combination
with better cross-strain-specific efficacy. Within the limits of the study
design, the ability of the PfAMA1 DiCo-Mix to induce cross-strain-specific
antibodies was not affected in all immunization groups, but the DiCo-PfRon2L
complexes did not improve the potency of PfAMA1-specific IgG responses.
PMID- 28702029
TI - Inflammation-Related Gene Polymorphisms Associated With Primary Immune
Thrombocytopenia.
AB - Primary immune thrombocytopenia (ITP) is an acquired autoimmune disease
characterized by a reduced platelet count and an increased risk of bleeding.
Although immense research has improved our understanding of ITP, the pathogenesis
remains unclear. Here, we investigated the involvement of 25 single-nucleotide
polymorphisms (SNPs) of the inflammation-related genes, including CD24, CD226,
FCRL3, IL2, IRF5, ITGAM, NLRP3, CARD8, PTPN22, SH2B2, STAT4, TNFAIP3, and TRAF1,
in the pathogenesis and treatment response of ITP. We recruited 312 ITP
inpatients and 154 healthy participants in this case-control study. Inflammation
related SNP genotyping was performed on the Sequenom MassARRAY iPLEX platform.
The expression of TNFAIP3 mRNA was determined by quantitative real-time RT-PCR.
All SNPs in healthy controls were consistent with Hardy-Weinberg equilibrium.
Statistical analysis revealed that rs10499194 in TNFAIP3 was significantly
associated with a decreased risk of ITP after Bonferroni multiple correction
(codominant, CT vs. CC, OR = 0.431, 95% CI = 0.262-0.711, p = 0.001; dominant,
TT/CT vs. CC, OR = 0.249, 95% CI = 0.141-0.440, p = 0.000). Besides, TNFAIP3
expression was significantly higher in patients with CT and pooled CT/TT
genotypes compared with CC genotype (p = 0.001; p = 0.001). Interestingly,
rs10499194 was also associated with corticosteroid-sensitivity (codominant, CT
vs. CC, OR = 0.092, 95% CI = 0.021-0.398, p = 0.001; dominant, TT/CT vs. CC, OR =
0.086, 95% CI = 0.020-0.369, p = 0.001; allelic, T vs. C, OR = 0.088, 95% CI =
0.021-0.372, p = 0.001). Furthermore, no significant association was found
between inflammation-related SNPs and the severity or refractoriness of ITP after
Bonferroni multiple correction. Our findings suggest that rs10499194 may be a
protective factor for susceptibility and corticosteroid sensitivity in ITP
patients.
PMID- 28702030
TI - Enrichment of HLA Types and Single-Nucleotide Polymorphism Associated With Non
progression in a Strictly Defined Cohort of HIV-1 Controllers.
AB - HIV-1 controllers (HIC) are extremely rare patients with the ability to control
viral replication, maintain unchanging CD4 T-cell count, and evade disease
progression for extensive periods of time, in the absence of antiretroviral
therapy. In order to establish the representation of key genetic correlates of
atypical disease progression within a cohort of HIV-1+ individuals who control
viral replication, we examine four-digit resolution HLA type and single
nucleotide polymorphisms (SNP) previously identified to be correlated to non
progressive infection, in strictly defined HIC. Clinical histories were examined
to identify patients exhibiting HIC status. Genomic DNA was extracted, and high
definition HLA typing and genome-wide SNP analysis was performed. Data were
compared with frequencies of SNP in European long-term non-progressors (LTNP) and
primary infection cohorts. HLA-B alleles associated with atypical disease
progression were at very high frequencies in the group of five HIC studied. All
four HIC of European ancestry were HLA-B*57+ and half were also HLA-B*27+. All
HIC, including one of self-reported African ethnicity, had the HLA-Cw*0602
allele, and the HLA-DQ9 allele was present only in HIC of European ancestry. A
median 95% of the top 19 SNP known to be associated with LTNP status was observed
in European HIC (range 78-100%); 17/19 of the SNP considered mapped to chromosome
6 in the HLA region, whereas 2/19 mapped to chromosome 8. The HIC investigated
here demonstrated high enrichment of HLA types and SNP previously associated with
long-term non-progression. These findings suggest that the extreme non
progressive phenotype considered here is associated with a genetic signature
characterized by a single-genetic unit centered around the HLA-B*57 haplotype and
the possible additive effect of HLA-B*27.
PMID- 28702031
TI - Alloantigen-Induced Regulatory T Cells Generated in Presence of Vitamin C Display
Enhanced Stability of Foxp3 Expression and Promote Skin Allograft Acceptance.
AB - Regulatory T cells (Tregs) are critical for the maintenance of immune homeostasis
and self-tolerance and can be therapeutically used for prevention of unwanted
immune responses such as allotransplant rejection. Tregs are characterized by
expression of the transcription factor Foxp3, and recent work suggests that
epigenetic imprinting of Foxp3 and other Treg-specific epigenetic signatures
genes is crucial for the stabilization of both Foxp3 expression and
immunosuppressive properties within Tregs. Lately, vitamin C was reported to
enhance the activity of enzymes of the ten-eleven translocation family, thereby
fostering the demethylation of Foxp3 and other Treg-specific epigenetic
signatures genes in developing Tregs. Here, we in vitro generated alloantigen
induced Foxp3+ Tregs (allo-iTregs) in presence of vitamin C. Although vitamin C
hardly influenced the transcriptome of allo-iTregs as revealed by RNA-seq, those
vitamin C-treated allo-iTregs showed a more pronounced demethylation of Foxp3 and
other Treg-specific epigenetic signatures genes accompanied with an enhanced
stability of Foxp3 expression. Accordingly, when being tested in vivo in an
allogeneic skin transplantation model, vitamin C-treated allo-iTregs showed a
superior suppressive capacity. Together, our results pave the way for the
establishment of novel protocols for the in vitro generation of alloantigen
induced Foxp3+ Tregs for therapeutic use in transplantation medicine.
PMID- 28702032
TI - NK Cell Exhaustion.
AB - Natural killer cells are important effector lymphocytes of the innate immune
system, playing critical roles in antitumor and anti-infection host defense.
Tumor progression or chronic infections, however, usually leads to exhaustion of
NK cells, thus limiting the antitumor/infection potential of NK cells. In many
tumors or chronic infections, multiple mechanisms might contribute to the
exhaustion of NK cells, such as dysregulated NK cell receptors signaling, as well
as suppressive effects by regulatory cells or soluble factors within the
microenvironment. Better understanding of the characteristics, as well as the
underlying mechanisms of NK cell exhaustion, not only should increase our
understanding of the basic biology of NK cells but also could reveal novel NK
cell-based antitumor/infection targets. Here, we provide an overview of our
current knowledge on NK cell exhaustion in tumors, and in chronic infections.
PMID- 28702033
TI - How Streptomyces anulatus Primes Grapevine Defenses to Cope with Gray Mold: A
Study of the Early Responses of Cell Suspensions.
AB - Gray mold, caused by Botrytis cinerea, is one of the most destructive diseases of
grapevine and is controlled with an intense application of fungicides. As
alternatives to chemicals, beneficial microbes may promote plant health by
stimulating the plant's immune system. An actinomycete, Streptomyces anulatus
S37, has been screened from the rhizosphere microbiome of healthy Vitis vinifera
on the basis of its ability to promote grapevine growth and to induce resistance
against various phytopathogens, including B. cinerea. However, molecular
mechanisms involved locally after direct perception of these bacteria by plant
cells still remain unknown. This study focuses on local defense events induced in
grapevine cells during interactions with S. anulatus S37 before and after
pathogen challenge. We demonstrated that S. anulatus S37 induced early responses
including oxidative burst, extracellular alkalinization, activation of protein
kinases, induction of defense gene expression and phytoalexin accumulation, but
not the programmed cell death. Interestingly, upon challenge with the B. cinerea,
the S. anulatus S37 primed grapevine cells for enhanced defense reactions with a
decline in cell death. In the presence of the EGTA, a calcium channel inhibitor,
the induced oxidative burst, and the protein kinase activity were inhibited, but
not the extracellular alkalinization, suggesting that Ca2+ may also contribute
upstream to the induced defenses. Moreover, desensitization assays using
extracellular pH showed that once increased by S. anulatus S37, cells became
refractory to further stimulation by B. cinerea, suggesting that grapevine cells
perceive distinctly beneficial and pathogenic microbes.
PMID- 28702034
TI - CaRDR1, an RNA-Dependent RNA Polymerase Plays a Positive Role in Pepper
Resistance against TMV.
AB - RNA silencing functions as a major natural antiviral defense mechanism in plants.
RNA-dependent RNA polymerases (RDRs) that catalyze the synthesis of double
stranded RNAs, are considered as a fundamental element in RNA silencing pathways.
In Arabidopsis thaliana, RDR1, 2 and 6 play important roles in anti-viral RNA
silencing. Expression of RDR1 can be elevated following plant treatment with
defense hormones and virus infection. RDR1 has been studied in several crop
species, but not in pepper (Capsicum annuum L.). Here, a RDR1 gene was isolated
from Capsicum annuum L., designated as CaRDR1. The full-length cDNA of CaRDR1 was
3,351 bp, encoding a 1,116-amino acid protein, which contains conserved regions,
such as the most remarkable motif DLDGD. The transcripts of CaRDR1 could be
induced by salicylic acid (SA), abscisic acid (ABA), H2O2, and tobacco mosaic
virus (TMV). Silencing of CaRDR1 in pepper resulted in increased susceptibility
to TMV as evident by severe symptom, increased of TMV-CP transcript, higher
malondialdehyde (MDA) content and lower antioxidant enzymes activities compared
with that of control plants. CaRDR1-overexpressing in Nicotiana benthamiana
showed mild disease symptom and reduced TMV-CP transcripts than that of empty
vector (EV) following TMV inoculation. The RNA silencing related genes, including
NbAGO2, NbDCL2, NbDCL3, and NbDCL4 elevated expression in overexpressed plants.
Alternative oxidase (AOX), the terminal oxidase of the cyanide (CN)-resistant
alternative respiratory pathway, catalyze oxygen-dependent oxidation of ubiquinol
in plants. It has an important function in plant defense against TMV. In
addition, CaRDR1 overexpression promoted the expression of NbAOX1a and NbAOX1b.
In conclusion, these results suggest that CaRDR1 plays a positive role in TMV
resistance by regulating antioxidant enzymes activities and RNA silencing-related
genes expression to suppress the replication and movement of TMV.
PMID- 28702035
TI - The Soybean Basic Helix-Loop-Helix Transcription Factor ORG3-Like Enhances
Cadmium Tolerance via Increased Iron and Reduced Cadmium Uptake and Transport
from Roots to Shoots.
AB - Cadmium (Cd) is one of the most dangerous heavy metal pollutants in the
environment and is toxic to animal and plant cells. On the other hand, iron (Fe)
is an essential element for plant growth and development. The chlorosis of plant
leaves under cadmium stress is similar to the typical symptom of iron deficiency.
Recently, several Arabidopsis basic/helix-loop-helix (bHLH) transcription factors
have been identified that are involved in the interactions between Cd and Fe. In
the present study, over-expression the ORG3-like gene GmORG3, a bHLH
transcription factor OBP3-responsive gene (ORG), enhanced Cd tolerance and
stabilized Fe homeostasis. The domain analysis of GmORG3 showed that the protein
contains a conserved 61-residue bHLH domain belonging to subfamily II. Moreover,
subcellular localization experiments showed that GmORG3 is a nucleoprotein.
GmORG3 was transcribed only in soybean roots and was significantly induced by
external Cd stress in soybean plants. Heterologous expression of GmORG3 enhanced
Cd tolerance in yeast. Furthermore, the overexpression of GmORG3 in soybean
mosaic seedlings using a hairy root system showed that overexpressing plants
increased the translocation ratio of Fe but reduced Cd translocation from the
roots to shoots. In addition, the ectopic expression of GmORG3 in tobacco reduced
phytotoxic effects induced by Cd stress and Fe deficiency, including the blockage
of root elongation and decreased chlorophyll content. By integrating all these
results, we found that GmORG3 plays an important role in response to Cd stress.
The results provide new insights into the molecular mechanisms of Cd tolerance in
soybean.
PMID- 28702036
TI - A FERONIA-Like Receptor Kinase Regulates Strawberry (Fragaria * ananassa) Fruit
Ripening and Quality Formation.
AB - Ripening of fleshy fruits is controlled by a series of intricate signaling
processes. Here, we report a FERONIA/FER-like receptor kinase, FaMRLK47, that
regulates both strawberry (Fragaria * ananassa) fruit ripening and quality
formation. Overexpression and RNAi-mediated downregulation of FaMRLK47 delayed
and accelerated fruit ripening, respectively. We showed that FaMRLK47 physically
interacts with FaABI1, a negative regulator of abscisic acid (ABA) signaling, and
demonstrated that FaMRLK47 regulates fruit ripening by modulating ABA signaling,
a major pathway governing strawberry fruit ripening. In accordance with these
findings, overexpression and RNAi-mediated downregulation of FaMRLK47 caused a
decrease and increase, respectively, in the ABA-induced expression of a series of
ripening-related genes. Additionally, overexpression and RNAi-mediated
downregulation of FaMRLK47 resulted in an increase and decrease in sucrose
content, respectively, as compared with control fruits, and respectively promoted
and inhibited the expression of genes in the sucrose biosynthesis pathway (FaSS
and FaSPS). Collectively, this study demonstrates that FaMRLK47 is an important
regulator of strawberry fruit ripening and quality formation, and sheds light on
the signaling mechanisms underlying strawberry fruit development and ripening.
PMID- 28702037
TI - Transcriptomic Response of Purple Willow (Salix purpurea) to Arsenic Stress.
AB - Arsenic (As) is a toxic element for plants and one of the most common
anthropogenic pollutants found at contaminated sites. Despite its severe effects
on plant metabolism, several species can accumulate substantial amounts of
arsenic and endure the associated stress. However, the genetic mechanisms
involved in arsenic tolerance remains obscure in many model plant species used
for land decontamination (phytoremediation), including willows. The present study
assesses the potential of Salix purpurea cv. 'Fish Creek' for arsenic
phytoextraction and reveals the genetic responses behind arsenic tolerance,
phytoextraction and metabolism. Four weeks of hydroponic exposure to 0, 5, 30 and
100 mg/L revealed that plants were able to tolerate up to 5 mg/L arsenic.
Concentrations of 0 and 5 mg/L of arsenic treatment were then used to compare
alterations in gene expression of roots, stems and leaves using RNA sequencing.
Differential gene expression revealed transcripts encoding proteins putatively
involved in entry of arsenic into the roots, storage in vacuoles and potential
transport through the plant as well as primary and secondary (indirect) toxicity
tolerance mechanisms. A major role for tannin as a compound used to relieve
cellular toxicity is implicated as well as unexpected expression of the cadmium
transporter CAX2, providing a potential means for internal arsenic mobility.
These insights into the underpinning genetics of a successful phytoremediating
species present novel opportunities for selection of dedicated arsenic tolerant
crops as well as the potential to integrate such tolerances into a wider Salix
ideotype alongside traits including biomass yield, biomass quality, low
agricultural inputs and phytochemical production.
PMID- 28702039
TI - CERES-Maize Model for Determining the Optimum Planting Dates of Early Maturing
Maize Varieties in Northern Nigeria.
AB - Field trials were carried out in the Sudan Savannah of Nigeria to assess the
usefulness of CERES-maize crop model as a decision support tool for optimizing
maize production through manipulation of plant dates. The calibration experiments
comprised of 20 maize varieties planted during the dry and rainy seasons of 2014
and 2015 at Bayero University Kano and Audu Bako College of Agriculture Dambatta.
The trials for model evaluation were conducted in 16 different farmer fields
across the Sudan (Bunkure and Garun-Mallam) and Northern Guinea (Tudun-Wada and
Lere) Savannas using two of the calibrated varieties under four different sowing
dates. The model accurately predicted grain yield, harvest index, and biomass of
both varieties with low RMSE-values (below 5% of mean), high d-index (above 0.8),
and high r-square (above 0.9) for the calibration trials. The time series data
(tops weight, stem and leaf dry weights) were also predicted with high accuracy
(% RMSEn above 70%, d-index above 0.88). Similar results were also observed for
the evaluation trials, where all variables were simulated with high accuracies.
Estimation efficiencies (EF)-values above 0.8 were observed for all the
evaluation parameters. Seasonal and sensitivity analyses on Typic Plinthiustalfs
and Plinthic Kanhaplustults in the Sudan and Northern Guinea Savannas were
conducted. Results showed that planting extra early maize varieties in late July
and early maize in mid-June leads to production of highest grain yields in the
Sudan Savanna. In the Northern Guinea Savanna planting extra-early maize in mid
July and early maize in late July produced the highest grain yields. Delaying
planting in both Agro-ecologies until mid-August leads to lower yields. Delaying
planting to mid-August led to grain yield reduction of 39.2% for extra early
maize and 74.4% for early maize in the Sudan Savanna. In the Northern Guinea
Savanna however, delaying planting to mid-August resulted in yield reduction of
66.9 and 94.3% for extra-early and early maize, respectively.
PMID- 28702038
TI - Neofusicoccum parvum Colonization of the Grapevine Woody Stem Triggers
Asynchronous Host Responses at the Site of Infection and in the Leaves.
AB - Grapevine trunk diseases cause important economic losses in vineyards worldwide.
Neofusicoccum parvum, one of the most aggressive causal agents of the trunk
disease Botryosphaeria dieback, colonizes cells and tissues of the grapevine
wood, leading to the formation of an internal canker. Symptoms then extend to
distal shoots, with wilting of leaves and bud mortality. Our aim was to
characterize the transcriptional dynamics of grapevine genes in the woody stem
and in the leaves during Neofusicoccum parvum colonization. Genome-wide
transcriptional profiling at seven distinct time points (0, 3, and 24 hours; 2,
6, 8, and 12 weeks) showed that both stems and leaves undergo extensive
transcriptomic reprogramming in response to infection of the stem. While most
intense transcriptional responses were detected in the stems at 24 hours, strong
responses were not detected in the leaves until the next sampling point at 2
weeks post-inoculation. Network co-expression analysis identified modules of co
expressed genes common to both organs and showed most of these genes were
asynchronously modulated. The temporal shift between stem vs. leaf responses
affected transcriptional modulation of genes involved in both signal perception
and transduction, as well as downstream biological processes, including oxidative
stress, cell wall rearrangement and cell death. Promoter analysis of the genes
asynchronously modulated in stem and leaves during N. parvum colonization
suggests that the temporal shift of transcriptional reprogramming between the two
organs might be due to asynchronous co-regulation by common transcriptional
regulators. Topology analysis of stem and leaf co-expression networks pointed to
specific transcription factor-encoding genes, including WRKY and MYB, which may
be associated with the observed transcriptional responses in the two organs.
PMID- 28702040
TI - Abscisic Acid Regulates Auxin Homeostasis in Rice Root Tips to Promote Root Hair
Elongation.
AB - Abscisic acid (ABA) plays an essential role in root hair elongation in plants,
but the regulatory mechanism remains to be elucidated. In this study, we found
that exogenous ABA can promote rice root hair elongation. Transgenic rice
overexpressing SAPK10 (Stress/ABA-activated protein kinase 10) had longer root
hairs; rice plants overexpressing OsABIL2 (OsABI-Like 2) had attenuated ABA
signaling and shorter root hairs, suggesting that the effect of ABA on root hair
elongation depends on the conserved PYR/PP2C/SnRK2 ABA signaling module.
Treatment of the DR5-GUS and OsPIN-GUS lines with ABA and an auxin efflux
inhibitor showed that ABA-induced root hair elongation depends on polar auxin
transport. To examine the transcriptional response to ABA, we divided rice root
tips into three regions: short root hair, long root hair and root tip zones; and
conducted RNA-seq analysis with or without ABA treatment. Examination of genes
involved in auxin transport, biosynthesis and metabolism indicated that ABA
promotes auxin biosynthesis and polar auxin transport in the root tip, which may
lead to auxin accumulation in the long root hair zone. Our findings shed light on
how ABA regulates root hair elongation through crosstalk with auxin biosynthesis
and transport to orchestrate plant development.
PMID- 28702041
TI - Characterization of BiP Genes from Pepper (Capsicum annuum L.) and the Role of
CaBiP1 in Response to Endoplasmic Reticulum and Multiple Abiotic Stresses.
AB - Adverse environmental conditions have a detrimental impact on crop growth and
development, and cause protein denaturation or misfolding. The binding protein
(BiP) plays an important protective role by alleviating endoplasmic reticulum
(ER) stress induced by misfolded proteins. In this study, we characterized three
BiP genes (CaBiP1, CaBiP2, and CaBiP3) in pepper, an economically important
vegetable and spice species. The role of CaBiP1 in plant tolerance to ER stress
and adverse environmental conditions (including heat, salinity, osmotic and
drought stress) were investigated. All the expected functional and signaling
domains were detected in three BiP proteins, but the motifs and exon-intron
distribution differed slightly in CaBiP3. CaBiP1 and CaBiP2 were constitutively
expressed in all the tested tissues under both normal and stressed conditions,
whereas CaBiP3 was mainly expressed following stress. Silencing of CaBiP1 reduced
pepper tolerance to ER stress and various environment stresses, and was
accompanied by increased H2O2 accumulation, MDA content, relative electric
leakage (REL), water loss rate, and a reduction in soluble protein content and
relative water content (RWC) in the leaves. Conversely, overexpression of CaBiP1
in Arabidopsis enhanced tolerance to ER stress and multiple environment stresses,
as demonstrated by an increase in germination rate, root length, survival rate,
RWC, the unfolded protein response (UPR) pathway, and a decrease in water loss
rate. Our results suggest that CaBiP1 may contribute to plant tolerance to
abiotic stresses by reducing ROS accumulation, increasing the water-retention
ability, and stimulating UPR pathways and expression of stress-related genes.
PMID- 28702042
TI - Characterization and Functional Analysis of the Poplar Pectate Lyase-Like Gene
PtPL1-18 Reveal Its Role in the Development of Vascular Tissues.
AB - Pectin is a major component of plant cell walls, and the structure of pectin
impacts on the properties of wood. Although we know that pectate lyase (PL, EC
4.2.2.2) has a major influence on the structure of pectin, our knowledge of
Pectate lyase-like genes (PLL) in tree species remains limited. To better
understand the characteristics of PLL genes in trees and to identify novel PLL
genes that are potentially involved in the development of wood, we performed
comprehensive analyses of gene structures, phylogenetic relationships,
chromosomal locations, gene duplication events, conserved protein motifs, and
gene expression patterns of 30 PLLs in Populus trichocarpa (PtPL1s). We performed
an in silico gene expression profiling and quantitative real-time PCR analysis
and found that most of the PtPL1 genes from subgroups Ia and Ib were highly
expressed in xylem. PtPL1-18 from subgroup Ia was preferentially expressed in
developing primary xylem and in xylem cells that were developing secondary walls.
Overexpression of PtPL1-18 in poplar reduced plant growth and xylem development.
Reduced secondary cell wall thickening and irregular xylem cells were observed in
the transgenic trees, probably due to their lower pectin content. Although pectin
is not a major component of plant secondary cell walls, our results are
consistent with the PtPL1 genes performing important functions during wood
formation.
PMID- 28702043
TI - Adoption of the 2A Ribosomal Skip Principle to Tobacco Mosaic Virus for Peptide
Display.
AB - Plant viruses are suitable as building blocks for nanomaterials and nanoparticles
because they are easy to modify and can be expressed and purified using plants or
heterologous expression systems. Plant virus nanoparticles have been utilized for
epitope presentation in vaccines, for drug delivery, as nanospheres and
nanowires, and for biomedical imaging applications. Fluorescent protein fusions
have been instrumental for the tagging of plant virus particles. The monomeric
non-oxygen-dependent fluorescent protein iLOV can be used as an alternative to
green fluorescent protein. In this study, the iLOV sequence was genetically fused
either directly or via a glycine-serine linker to the C-terminus of the Tobacco
mosaic virus (TMV) coat protein (CP) and also carried an N-terminal Foot-and
mouth disease virus (FMDV) 2A sequence. Nicotiana benthamiana plants were
inoculated with recombinant viral vectors and a systemic infection was achieved.
The presence of iLOV fusion proteins and hybrid particles was confirmed by
western blot analysis and transmission electron microscopy. Our data suggest that
TMV-based vectors are suitable for the production of proteins at least as large
as iLOV when combined with the FMDV 2A sequence. This approach allowed the
simultaneous production of foreign proteins fused to the CP as well as free CP
subunits.
PMID- 28702044
TI - Leaf Spectral Reflectance Shows Thalassia testudinum Seedlings More Sensitive to
Hypersalinity than Hyposalinity.
AB - Thalassia testudinum (turtle grass) is the dominant and climax-successional
seagrass species in the subtropical/tropical Atlantic and Caribbean region. Two
die-offs of T. testudinum in Florida Bay, United States have raised concerns
regarding the resilience of this species to environmental disturbances. Seedlings
are important in recovery of T. testudinum, following disturbance events. Leaf
spectral reflectance [R(lambda)] was measured in T. testudinum seedlings exposed
for 2 weeks to three salinities (20, 35, and 50) and two light levels (full sun
and 50-70% light reduction) in experimental mesocosms. Multivariate analyses
indicated that hypersalinity had a greater effect on spectral reflectance than
hyposalinity or light reduction. There was an increase in variability and
flattening of reflectance spectra at the highest salinity. All three salinity
treatments had distinct reflectance spectra across green wavelengths (530-580
nm), with additional discrimination between 20 versus 50 and 35 versus 50
treatments across red wavelengths (630-690 nm). Red:Green reflectance ratios were
highest and photochemical reflective index values were lowest for the salinity 50
treatment, but were not significantly different between the salinity 20 and 35
treatments. The changes in the R(lambda) spectra for the salinity 50 seedlings
were consistent with previously observed reductions in leaf pigments and maximum
photochemical efficiency of photosystem II. These observations indicate that leaf
spectral reflectance is a sensitive indicator of plant stress in T. testudinum
seedlings and that seedlings are more sensitive to short-term exposures to
hypersalinity than hyposalinity.
PMID- 28702045
TI - Functional Characterization of TaFUSCA3, a B3-Superfamily Transcription Factor
Gene in the Wheat.
AB - The end-use quality of wheat, including its unique rheology and viscoelastic
properties, is predominantly determined by the composition and concentration of
gluten proteins. While, the mechanism regulating expression of the seed storage
protein (SSP) genes and other related genes in wheat remains unclear. In this
study, we report on the cloning and functional identification of TaFUSCA3, a B3
superfamily transcription factor (TF) gene in wheat. Sequence alignment indicated
that wheat and barley FUSCA3 genes are highly conserved. Quantitative reverse
transcription (qRT)-PCR analysis showed that the transcript of TaFUSCA3 was
accumulated mostly in the stamens and the endosperms of immature wheat seeds.
Yeast-one-hybrid results proved that the full-length TaFUSCA3 and its C-terminal
region had transcriptional activities. Yeast-two-hybrid and bimolecular
fluorescence complementation assays indicated that TaFUSCA3 could activate the
expression of the high molecular weight glutenin subunit gene Glu-1Bx7 and
interact with the seed-specific bZIP protein TaSPA. DNA-protein-interaction
enzyme-linked immunosorbent assay demonstrated that TaFUSCA3 specifically
recognizes the RY-box of the Glu-1Bx7 promoter region. Transient expression
results showed that TaFUSCA3 could trans-activate the Glu-1Bx7 promoter, which
contains eight RY-box sequences. TaFUSCA3 was unable to activate the downstream
transcription when the RY-box was fully mutated. TaFUSCA3 could activate the
transcription of the At2S3 gene promoter in a complementation of loss-of-function
experiment using the Arabidopsis thaliana line fus3-3, which is a FUSCA3 mutant,
demonstrating the evolutionary conservation of the TaFUSCA3 gene. In conclusion,
the wheat B3-type TF, TaFUSCA3, is functional conserved between monocot and
dicot, and could regulate SSP gene expression by interacting specifically with
TaSPA.
PMID- 28702046
TI - Selection and Validation of Appropriate Reference Genes for qRT-PCR Analysis in
Isatis indigotica Fort.
AB - Due to its sensitivity and specificity, real-time quantitative PCR (qRT-PCR) is a
popular technique for investigating gene expression levels in plants. Based on
the Minimum Information for Publication of Real-Time Quantitative PCR Experiments
(MIQE) guidelines, it is necessary to select and validate putative appropriate
reference genes for qRT-PCR normalization. In the current study, three
algorithms, geNorm, NormFinder, and BestKeeper, were applied to assess the
expression stability of 10 candidate reference genes across five different
tissues and three different abiotic stresses in Isatis indigotica Fort.
Additionally, the IiYUC6 gene associated with IAA biosynthesis was applied to
validate the candidate reference genes. The analysis results of the geNorm,
NormFinder, and BestKeeper algorithms indicated certain differences for the
different sample sets and different experiment conditions. Considering all of the
algorithms, PP2A-4 and TUB4 were recommended as the most stable reference genes
for total and different tissue samples, respectively. Moreover, RPL15 and PP2A-4
were considered to be the most suitable reference genes for abiotic stress
treatments. The obtained experimental results might contribute to improved
accuracy and credibility for the expression levels of target genes by qRT-PCR
normalization in I. indigotica.
PMID- 28702047
TI - Transcriptome Analysis of Al-Induced Genes in Buckwheat (Fagopyrum esculentum
Moench) Root Apex: New Insight into Al Toxicity and Resistance Mechanisms in an
Al Accumulating Species.
AB - Relying on Al-activated root oxalate secretion, and internal detoxification and
accumulation of Al, buckwheat is highly Al resistant. However, the molecular
mechanisms responsible for these processes are still poorly understood. It is
well-known that root apex is the critical region of Al toxicity that rapidly
impairs a series of events, thus, resulting in inhibition of root elongation.
Here, we carried out transcriptome analysis of the buckwheat root apex (0-1 cm)
with regards to early response (first 6 h) to Al stress (20 MUM), which is
crucial for identification of both genes and processes involved in Al toxicity
and tolerance mechanisms. We obtained 34,469 unigenes with 26,664 unigenes
annotated in the NCBI database, and identified 589 up-regulated and 255 down
regulated differentially expressed genes (DEGs) under Al stress. Functional
category analysis revealed that biological processes differ between up- and down
regulated genes, although 'metabolic processes' were the most affected category
in both up- and down-regulated DEGs. Based on the data, it is proposed that Al
stress affects a variety of biological processes that collectively contributes to
the inhibition of root elongation. We identified 30 transporter genes and 27
transcription factor (TF) genes induced by Al. Gene homology analysis highlighted
candidate genes encoding transporters associated with Al uptake, transport,
detoxification, and accumulation. We also found that TFs play critical role in
transcriptional regulation of Al resistance genes in buckwheat. In addition, gene
duplication events are very common in the buckwheat genome, suggesting a possible
role for gene duplication in the species' high Al resistance. Taken together, the
transcriptomic analysis of buckwheat root apex shed light on the processes that
contribute to the inhibition of root elongation. Furthermore, the comprehensive
analysis of both transporter genes and TF genes not only deep our understanding
on the responses of buckwheat roots to Al toxicity but provide a good start for
functional characterization of genes critical for Al tolerance.
PMID- 28702048
TI - Aegilops tauschii Accessions with Geographically Diverse Origin Show Differences
in Chromosome Organization and Polymorphism of Molecular Markers Linked to Leaf
Rust and Powdery Mildew Resistance Genes.
AB - Aegilops tauschii (2n = 2x = 14) is a diploid wild species which is reported as a
donor of the D-genome of cultivated bread wheat. The main goal of this study was
to examine the differences and similarities in chromosomes organization among
accessions of Ae. tauschii with geographically diversed origin, which is believed
as a potential source of genes, especially determining resistance to fungal
diseases (i.e., leaf rust and powdery mildew) for breeding of cereals. We
established and compared the fluorescence in situ hybridization patterns of 21
accessions of Ae. tauschii using various repetitive sequences mainly from the BAC
library of wheat cultivar Chinese Spring. Results obtained for Ae. tauschii
chromosomes revealed many similarities between analyzed accessions, however, some
hybridization patterns were specific for accessions, which become from cognate
regions of the World. The most noticeable differences were observed for
accessions from China which were characterized by presence of distinct signals of
pTa-535 in the interstitial region of chromosome 3D, less intensity of pTa-86
signals in chromosome 2D, as well as lack of additional signals of pTa-86 in
chromosomes 1D, 5D, or 6D. Ae. tauschii of Chinese origin appeared homogeneous
and separate from landraces that originated in western Asia. Ae. tauschii
chromosomes showed similar hybridization patterns to wheat D-genome chromosomes,
but some differences were also observed among both species. What is more, we
identified reciprocal translocation between short arm of chromosome 1D and long
arm of chromosome 7D in accession with Iranian origin. High polymorphism between
analyzed accessions and extensive allelic variation were revealed using molecular
markers associated with resistance genes. Majority of the markers localized in
chromosomes 1D and 2D showed the diversity of banding patterns between
accessions. Obtained results imply, that there is a moderate or high level of
polymorphism in the genome of Ae. tauschii determined by a geographical origin,
which we proved by cytogenetic and molecular markers analysis. Therefore,
selected accessions might constitute an accessible source of variation for
improvement of Triticeae species like wheat and triticale.
PMID- 28702049
TI - Endurance Exercise Ability in the Horse: A Trait with Complex Polygenic
Determinism.
AB - Endurance horses are able to run at more than 20 km/h for 160 km (in bouts of 30
40 km). This level of performance is based on intense aerobic metabolism,
effective body heat dissipation and the ability to endure painful exercise. The
known heritabilities of endurance performance and exercise-related physiological
traits in Arabian horses suggest that adaptation to extreme endurance exercise is
influenced by genetic factors. The objective of the present genome-wide
association study (GWAS) was to identify single nucleotide polymorphisms (SNPs)
related to endurance racing performance in 597 Arabian horses. The performance
traits studied were the total race distance, average race speed and finishing
status (qualified, eliminated or retired). We used three mixed models that
included a fixed allele or genotype effect and a random, polygenic effect.
Quantile-quantile plots were acceptable, and the regression coefficients for
actual vs. expected log10p-values ranged from 0.865 to 1.055. The GWAS revealed
five significant quantitative trait loci (QTL) corresponding to 6 SNPs on
chromosomes 6, 1, 7, 16, and 29 (two SNPs) with corrected p-values from 1.7 * 10
6 to 1.8 * 10-5. Annotation of these 5 QTL revealed two genes: sortilin-related
VPS10-domain-containing receptor 3 (SORCS3) on chromosome 1 is involved in
protein trafficking, and solute carrier family 39 member 12 (SLC39A12) on
chromosome 29 is active in zinc transport and cell homeostasis. These two coding
genes could be involved in neuronal tissues (CNS). The other QTL on chromosomes
6, 7, and 16 may be involved in the regulation of the gene expression through non
coding RNAs, CpG islands and transcription factor binding sites. On chromosome 6,
a new candidate equine long non-coding RNA (KCNQ1OT1 ortholog: opposite antisense
transcript 1 of potassium voltage-gated channel subfamily Q member 1 gene) was
predicted in silico and validated by RT-qPCR in primary cultures of equine
myoblasts and fibroblasts. This lncRNA could be one element of the cardiac rhythm
regulation. Our GWAS revealed that equine performance during endurance races is a
complex polygenic trait, and is partially governed by at least 5 QTL: two coding
genes involved in neuronal tissues and three other loci with many regulatory
functions such as slowing down heart rate.
PMID- 28702050
TI - Circulating MicroRNAs in Serum from Cattle Challenged with Bovine Viral Diarrhea
Virus.
AB - Bovine viral diarrhea virus (BVDV) is an RNA virus that is often associated with
respiratory disease in cattle. MicroRNAs have been proposed as indicators of
exposure to respiratory pathogens. The objective of this study was to identify
microRNAs in cattle that had been challenged with a non-cytopathic field strain
of BVDV. Five colostrum deprived neonate Holstein calves were inoculated with
BVDV (challenged) and 4 were mock challenged (control). Serum from all calves was
collected at four different times: prior to challenge (day 0) and at 4, 9, and 16
days post-challenge. RNA was extracted from sera, and expression, via read
counts, of small non-coding RNAs were obtained using next-generation sequencing.
A total of 905,861 sequences identified 427 microRNAs. Sixty-two microRNAs had
>1,000 total reads across all samples. Bta-miR-339a, bta-miR-185, bta-miR-486,
Bta-miR-92a, bta-miR-30e-5p, bta-let-7c, and bta-miR-2284x were significantly
different (P < 0.05) across time regardless of challenge status. Bta-miR-423-5p
(P = 0.008) and bta-miR-151-3p (P = 0.005) were significantly different between
challenged and control animals across time. In challenged animals, bta-miR-423-5p
peaked in number of reads by day 4 and steadily declined from day 4 to day 16. In
control animals, bta-miR-423-5p declined from day 0 to day 9 and increased in
number by day 16. By day 16, both challenged and control animals had similar
levels of bta-miR-423-5p, and these levels were similar to day 0 levels. Bta-miR
151-3p peaked at day 9 in challenged animals, while control animals decreased
across time. By day 16, the number of reads of bta-miR-151-3p were similar
between challenged and control animals. The level in challenged animals had
returned to day 0 levels by day 16, whereas the levels for control animals was
significantly lower (P = 0.006) than day 0. Further studies are needed to
establish if bta-miR-423-5p or bta-miR-151-3p could be used as a biomarker for
exposure to BVDV.
PMID- 28702051
TI - Random Forest-Based Approach for Maximum Power Point Tracking of Photovoltaic
Systems Operating under Actual Environmental Conditions.
AB - Many maximum power point tracking (MPPT) algorithms have been developed in recent
years to maximize the produced PV energy. These algorithms are not sufficiently
robust because of fast-changing environmental conditions, efficiency, accuracy at
steady-state value, and dynamics of the tracking algorithm. Thus, this paper
proposes a new random forest (RF) model to improve MPPT performance. The RF model
has the ability to capture the nonlinear association of patterns between
predictors, such as irradiance and temperature, to determine accurate maximum
power point. A RF-based tracker is designed for 25 SolarTIFSTF-120P6 PV modules,
with the capacity of 3 kW peak using two high-speed sensors. For this purpose, a
complete PV system is modeled using 300,000 data samples and simulated using the
MATLAB/SIMULINK package. The proposed RF-based MPPT is then tested under actual
environmental conditions for 24 days to validate the accuracy and dynamic
response. The response of the RF-based MPPT model is also compared with that of
the artificial neural network and adaptive neurofuzzy inference system algorithms
for further validation. The results show that the proposed MPPT technique gives
significant improvement compared with that of other techniques. In addition, the
RF model passes the Bland-Altman test, with more than 95 percent acceptability.
PMID- 28702052
TI - Serum Concentrations of Betatrophin and Its Association with Indirect Indices of
Insulin Resistance and Beta Cell Function in Women with Polycystic Ovary
Syndrome.
AB - INTRODUCTION: Data underline the role of betatrophin in glucose homeostasis.
Polycystic ovary syndrome (PCOS) is characterized by insulin resistance (IR). The
aim of our study was to investigate the relationship of serum betatrophin
concentrations with indirect indices of IR and insulin secretion in women with
PCOS, compared to the control group. METHODS: The study group comprised 43 women
with PCOS and 16 controls. IR was assessed by HOMA-IR and Matsuda index. Insulin
secretion was evaluated with HOMA-B. An oral glucose tolerance test (OGTT) with
estimation of serum betatrophin concentrations was performed. RESULTS: Glucose
load resulted in an increase in serum betatrophin concentrations in the control
group (p = 0.02). Serum betatrophin concentrations at 120 min of OGTT were lower
in women with PCOS than in the control group (p = 0.02). We observed positive
correlations between baseline serum betatrophin concentrations and HOMA-IR (r =
0.39, p = 0.008), negative correlations with Matsuda index (r = -0.31, p =
0.004), and a positive relationship with HOMA-B (r = 0.38, p = 0.01) in women
with PCOS. Multiple regression analysis revealed that HOMA-B (beta = 0.47, p =
0.001) was an independent factor connected to serum betatrophin levels in PCOS.
CONCLUSIONS: Serum concentrations of betatrophin are connected with insulin
resistance and beta cell function and did not change after glucose load in women
with PCOS.
PMID- 28702053
TI - Etiology of Hypopituitarism in Adult Patients: The Experience of a Single Center
Database in the Serbian Population.
AB - There are only a few published studies related to the population-based etiology
of hypopituitarism. New risks for developing hypopituitarism have been recognized
in the last 10 years. Aim. To present data regarding the etiology of
hypopituitarism collected in a tertiary center over the last decade. This is a
cross-sectional database study. Patients and Methods. We included 512 patients
(pts) with hypopituitarism, with a mean age of 45.9 +/- 1.7 yrs (range: 18-82;
male: 57.9%). Results. Nonfunctional pituitary adenomas were presented in 205 pts
(40.5%), congenital causes in 74 pts (14.6%), while acromegaly and prolactinomas
were presented in 37 (7.2%) and 36 (7.0%) patients, respectively.
Craniopharyngiomas were detected in 30 pts (5.9%), and head trauma due to trauma
brain injury-TBI and subarachnoid hemorrhage-SAH in 27 pts (5.4%). Survivors of
hemorrhagic fever with renal syndrome (HFRS) and those with previous cranial
irradiation were presented in the same frequency (18 pts, 3.5% each). Conclusion.
The most common causes of hypopituitarism in our database are pituitary adenomas.
Increased awareness of the other causes of pituitary dysfunction, such as
congenital, head trauma, extrapituitary cranial irradiation, and infections, is
the reason for a higher frequency of these etiologies of hypopituitarism in the
presented database.
PMID- 28702054
TI - The Role of Neighborhood Characteristics in Late Stage Melanoma Diagnosis among
Hispanic Men in California, Texas, and Florida, 1996-2012.
AB - BACKGROUND: Hispanics diagnosed with cutaneous melanoma are more likely to
present at advanced stages but the reasons for this are unknown. We identify
census tracts at high risk for late stage melanoma diagnosis (LSMD) and examine
the contextual predictors of LSMD in California, Texas, and Florida. METHODS: We
conducted a cross-sectional study using geocoded state cancer registry data.
Using hierarchical multilevel logistic regression models we estimated ORs and 95%
confidence intervals for the impact of socioeconomic, Hispanic ethnic
concentration, index of dissimilarity, and health resource availability measures
on LSMD. RESULTS: We identified 12,493 cases. In California, late stage cases
were significantly more likely to reside within census tracts composed mostly of
Hispanics and immigrants. In Texas, LSMD was associated with residence in areas
of socioeconomic deprivation and a higher proportion of immigrants. In Florida,
living in areas of low education attainment, high levels of poverty, and a high
percentage of Hispanic residents was significantly associated with LSMD.
Residential segregation did not independently affect LSMD. CONCLUSION: The
influence of contextual predictors on LSMD varied in magnitude and strength by
state, highlighting both the cosegregation of social adversity and poverty and
the complexity of their interactions.
PMID- 28702055
TI - Evaluation of Sensibility Threshold for Interocclusal Thickness of Patients
Wearing Complete Dentures.
AB - OBJECTIVE: The aim of this study was to evaluate sensibility threshold for
interocclusal thickness in experienced and nonexperienced denture wearers after
the insertion of new complete dentures. MATERIALS AND METHODS: A total of 88
patients with complete dentures have participated in this study. The research was
divided into two experimental groups, compared with the previous experience
prosthetic dental treatment. The sensibility threshold for interocclusal
thickness was measured with metal foil with 8 MUm thickness and width of 8 mm,
placed between the upper and lower incisor region. Statistical analysis was
performed using standard software package BMDP (biomedical statistical package).
RESULTS: Results suggest that time of measurement affects the average values of
the sensibility threshold for interocclusal thickness (F = 242.68, p = 0.0000).
Gender appeared to be a significant factor when it interacted with time
measurement resulting in differences in sensibility threshold for interocclusal
thickness (gender: F = 9.84, p = 0.018; F = 4.83, p = 0.0003). CONCLUSION: The
sensibility threshold for interocclusal thickness was the most important
functional adaptation in patient with complete dentures. A unique trait of this
indicator is the progressive reduction of initial values and a tendency to
reestablish the stationary state in the fifteenth week after dentures is taken
off.
PMID- 28702056
TI - Prevalence of dental caries and fluoride concentration of drinking water: A
systematic review.
AB - BACKGROUND: The objective of this study was to systematically review prevalence
of dental caries at different water fluoride levels and emphasize fluoride
concentration of drinking water and prevalence of dental caries. MATERIALS AND
METHODS: A comprehensive study was conducted using PubMed database. Inclusion
criteria were predefined and some articles fulfilled these criteria. Study
validity was assessed by some checklists. Surveys were conducted to determine
prevalence of dental caries among individuals. RESULTS: The heterogeneity in the
group of children with deciduous teeth in terms of the amount of fluoride in
drinking water and social class was significant, and the results of the studies
in all the subgroups could not be pooled. However, the heterogeneity of group 2
for subjects with permanent teeth in terms of the fluoride level in drinking
water and social class was not significant, and the results of the studies in
each subgroup could be pooled together. CONCLUSION: The meta-regression showed
that tooth type and social class had a significant association with the
difference in the prevalence of dental caries. Therefore, these variables were
the sources of heterogeneity, and the studies must be grouped and subgrouped
based on these variables.
PMID- 28702057
TI - Role of fluoride varnish in preventing early childhood caries: A systematic
review.
AB - BACKGROUND: Early childhood caries is a public health problem that continues to
affect babies and preschool children worldwide. This untreated caries process
results in progressive destruction of the crowns of the teeth, often accompanied
by severe pain and suffering, affecting the quality of life. Fluoride varnish
which is one of the most important materials to prevent ECC is easy to apply and
well tolerated by children. This study aimed to evaluate the scientific evidence
regardingthe role of fluoride varnish in preventing early childhood caries.
MATERIALS AND METHODS: Records were searched from various databases such as
PubMed/Medline, Cochrane, and EMBASE. Articles published over the past 36 years
(1979-2015) were identified using the key search terms. A total of 190 records
were identified by title/abstracts/full text articles and were retrieved.
Potentially relevant reports identified from the reference lists of relevant
studies, review articles and chapters were hand-searched, which yielded an
additional 10 articles. The main outcome of our investigation was prevention of
early childhood caries following application of fluoride varnish and unavoidable
fluoride exposure. Out of 190 articles originally identified, 30 records were
considered potentially eligible and sought for further assessment. 17 articles
met the inclusion criteria and these studies were assessed independently for
methodology and performance. RESULTS: Analysis of literature revealed that
basically two concentrations of fluoride varnishes have been used: 1% and 5%,
with a caries preventive fraction ranges of 6.4-30% and 5-63%, respectively.
CONCLUSION: The results showed that fluoride varnishes have been used at
concentrations of 1% and 5% in the prevention of ECC. The preventive fraction was
influenced by the frequency of application, the duration of study and sample
size. The evidence level of the studies was of moderate to limited value.
PMID- 28702058
TI - Effectiveness of audiovisual distraction in behavior modification during dental
caries assessment and sealant placement in children with autism spectrum
disorder.
AB - BACKGROUND: The aim of this study was to evaluate the effectiveness of
audiovisual (AV) distraction in behavior modification during dental caries
assessment and sealant placement in children with autism spectrum disorder.
MATERIALS AND METHODS: This study was conducted on 28 children diagnosed with
autism spectrum disorder, aged 6.5-9.8 years. Children underwent one introductory
(desensitization) appointment and three treatment sessions. During the
introductory session, children had the procedures explained to them, they watched
a movie projected on a screen while oral screening and assessment of cooperation
level were carried out. In treatment session I, oral examination, charting, and
dental x-rays were undertaken, whereas the children watched movies with or
without video eyewear. During treatment sessions II/III, dental prophylaxis was
carried out on upper and lower jaws in addition to the application of dental
sealants on the right upper and lower and the left upper and lower permanent
molars, respectively, while the children were distracted by cartoon movies using
video eyewear. Changes in pulse oximeter and heart rate were recorded every 5
min. Independent samples t-test was used to assess the significance of changes in
pulse and O2 saturation levels during each visit. RESULTS: International Caries
Detection and Assessment System-code 2 was found to be the most prevalent (n =
58; 52%). A significant difference (P < 0.02) was observed in mean heart rate
during dental screening of the upper and lower jaws with and without video
eyewear. A decrease was observed in the mean heart rate during subsequent
treatment sessions. CONCLUSION: Initial desensitization appointment and "tell
show-do" approach, followed by short and positive treatment sessions, assisted in
gaining cooperation and improving behavior in the subjects. Video eyewear
distraction proved an effective tool in managing children with autism spectrum
disorder during noninvasive preventive dental procedures.
PMID- 28702059
TI - Preferences and choices of a child concerning the environment in a pediatric
dental operatory.
AB - BACKGROUND: The aim of this cross-sectional descriptive study was to determine
children's preferences in a dental clinic so as to reduce anxiety during dental
procedures. In this study survey methodology was used. MATERIALS AND METHODS: A
questionnaire was designed to evaluate the child's preference in a dental
hospital so as to remove anxiety during a dental procedure. This study was
carried out on 50 children aged 6-10 years. The children were randomly selected
based on their first dental visit in a private dental college. RESULTS: A large
number of children preferred listening to rhymes and watching cartoons while
undergoing dental treatment. They also preferred the walls painted with cartoons,
the dental chair full of toys, a scented environment, and the presence of their
parents during the treatment. CONCLUSION: The results of this study will help the
dental team decide on the appropriate design of the pediatric dental operatory
room in order to provide a comfortable dental environment which will reduce
anxiety in children and improve the quality of health care.
PMID- 28702060
TI - Oral health status, salivary pH status, and Streptococcus mutans counts in dental
plaques and saliva of children with acute lymphoblastic leukemia.
AB - BACKGROUND: Acute lymphoblastic leukemia (ALL), accounting for 23% of all
malignancies in children, is the most prevalent pediatric malignancy. This study
compared dental caries, oral hygiene status, salivary pH, and Streptococcus
mutans counts in dental plaques and saliva of children with leukemia with those
of healthy controls. MATERIALS AND METHODS: This case-control cross-sectional
study assessed 32 children with ALL and 32 healthy children (4-9-year-old) for
gingival bleeding index (GBI), decayed, missing, and filled/decayed, missing, and
filled surfaces (DMF/dmfs), and plaque index (PI). Sampling was performed to
determine salivary pH and S. mutans counts of the participants. The two groups
matched in terms of age, gender, and socioeconomic status. The groups were
compared using independent t-test, Mann-Whitney test, Chi-square test, and
Spearman's and Pearson's correlation analyses. RESULTS: The mean DMF/dmfs and GBI
were significantly higher in the ALL group (PDMF/dmfs= 0.03; PGBI= 0.04).
However, the two groups were not significantly different in the mean PI values (P
= 0.47). The mean S. mutans counts in dental plaques and saliva of the children
with leukemia were significantly lower than the healthy controls (P < 0.01).
Moreover, the mean salivary pH was significantly lower in the ALL group compared
to the control group (P < 0.01). CONCLUSION: Higher caries and gingival bleeding
rates, higher dental plaque accumulation in children with ALL, decreased salivary
pH, and cumulative effects of other risk factors highlight the significance of
oral hygiene training programs (for the parents of these children) and regular
dental examinations for these children.
PMID- 28702061
TI - The effect of surface treatment with a fractional carbon dioxide laser on shear
bond strength of resin cement to a lithium disilicate-based ceramic.
AB - BACKGROUND: This study investigated the impact of different surface treatments,
including fractional carbon dioxide (CO2) laser on shear bond strength (SBS) of
resin cement to lithium disilicate ceramic. MATERIALS AND METHODS: In this in
vitro study, 72 blocks of IPS e.max CAD ceramic were randomly divided into six
groups in terms of treatment (n = 12). Group 1 underwent etching with 9.6%
hydrofluoric (HF) acid, whereas group 2 was subjected to air abrasion with
aluminum oxide particles. Groups 3 and 4 were treated with a fractional CO2 laser
for 10 s using 10 W/14 mJ (group 3) or 20 W/10 mJ (group 4). In groups 5 and 6,
the CO2 laser was applied similar to that in groups 3 and 4, respectively; then,
the specimens were etched by HF acid. After silane application, luting cement was
bonded to the specimens. The SBS was assessed with a universal testing machine,
and the type of bond failure was determined. Data were analyzed by ANOVA, Duncan,
and Fisher's exact tests. RESULTS: Surface conditioning with fractional CO2 laser
alone resulted in significantly lower SBS than HF acid treatment (P < 0.05). Bond
strengths of the specimens treated with a combination of laser irradiation and
acid etching were significantly greater than all the other groups (P < 0.05). No
significant difference was found in the distribution of failure modes among the
groups (P = 0.337). CONCLUSION: The combination of fractional CO2 laser
irradiation and HF acid etching could be recommended when extra retention is
required for lithium disilicate-based restorations, whereas laser treatment alone
cannot produce sufficient SBS.
PMID- 28702062
TI - Jargon: A barrier in case history taking? - A cross-sectional survey among dental
students and staff.
AB - BACKGROUND: The use of jargon has become very common in the healthcare field,
especially in medical/dental records. Although the use of standard medical jargon
can be seen as professional, efficient shorthand, a lack of awareness regarding
the standard medical abbreviations and incessant and overzealous use of slang
among the healthcare professionals can act as a barrier to effective
communication and understanding among patients and peers. The aim of this study
was to assess the acceptance and use of jargon in case history taking among
clinical dental students and dental teaching faculty members of dental colleges
in Ernakulam and Idukki districts of Kerala. MATERIALS AND METHODS: A cross
sectional questionnaire-based survey was carried out, consisting of 15 questions,
to assess the objectives of the study. The study was conducted among clinical
dental undergraduate students, house surgeons, postgraduate students and teaching
faculty members of five dental colleges in Ernakulam and Idukki districts,
Kerala. The results were expressed as a number and percentage of response for
each question and Chi-squared test was used for inferential statistical analysis.
RESULTS: All the 549 respondents used jargon in case history taking.
Approximately 22.4% of the respondents admitted that they always used jargon and
55.8% admitted of using jargon only when there was a lack of time. The majority
of the respondents (71.4%) learned the jargon from their colleagues.
Approximately 50% of the respondents admitted use of jargon in a history section
and about 32% of the respondents in all the sections of case history taking.
Approximately 74% were of the opinion that abbreviations should be permitted in
case history taking. CONCLUSION: This study showed widespread use of
jargon/abbreviations in case history taking among the respondents. There is a
lack of knowledge regarding standard medical abbreviations. Although the majority
of the respondents were comfortable with the use of jargon, the majority of the
postgraduates and faculty members felt the use of jargon should be stopped.
PMID- 28702063
TI - Salivary levels of interleukin-8 in oral lichen planus and diabetic patients: A
biochemical study.
AB - BACKGROUND: This study aimed to assess the salivary levels of interleukin-8 (IL
8) in oral lichen planus (OLP) and diabetes mellitus (DM) patients, and OLP + DM
patients in comparison with healthy individuals. MATERIALS AND METHODS: This
descriptive cross-sectional study was conducted on 75 patients (30 with OLP, 5
with both OLP and DM, 20 with DM and 20 healthy controls). The salivary levels of
IL-8 and fasting blood sugar and 2-h postprandial blood glucose levels were
measured in all the subjects. Data were analyzed with one-way ANOVA and post hoc
least significant difference tests. RESULTS: The mean salivary level of IL-8 was
the highest in OLP + DM patients, followed by DM, OLP and control groups,
respectively. Pair-wise comparisons of the groups revealed significant
differences in the salivary levels of IL-8 between OLP and control, DM and
control, also OLP + DM patients and control (P < 0.05). CONCLUSION: The
increasing salivary level of IL-8 in the control, OLP, DM, OLP + DM groups,
respectively, indicates the role of this inflammatory cytokine in the
pathogenesis of OLP and diabetes.
PMID- 28702064
TI - Osseous choristoma of submental region: A rare occurrence.
AB - Osseous choristoma is a rare, benign lesion of the oral cavity. This report
presents a case of osseous choristoma in the submental region of a 30-year-old
female subject. Her chief complaint was a painless swelling in the submental
region. Panoramic radiography showed a well-defined, round, radiopaque lesion
near the inferior border of the left mental region. The lesion was diagnosed as
an osseous choristoma based on the histopathological examination of the surgical
specimen. This paper is an attempt to bring forward a unique occurrence of
osseous choristoma, which would further help the medical fraternity in
improvising their knowledge, diagnosis, and treatment of this entity.
PMID- 28702065
TI - Achondroplasia with multiple supplemental supernumerary teeth and multiple talon
cusps: A rare case report.
AB - Achondroplasia is the most common cause of dwarfism, which is inherited as an
autosomal dominant disorder, caused by genetic mutation in fibroblast growth
factor 3, leading to defective maturation of chondrocytes. It is known to be
associated with various oral and dental manifestations such as delayed dental
development, midfacial hypoplasia and constricted maxilla with a relatively large
mandible, resulting in skeletal/dental Class III malocclusion, posterior
crossbite, anterior reverse jet and anterior overbite. However, the association
of achondroplasia with talon cusp and supernumerary teeth has never been reported
in the literature. Wehereby reported a case of achondroplasia associated with
such unusual findings. Moreover, all the three variants of talon cusp, i.e.,
"true talon,""semitalon" and "trace talon" are observed in the present case,
which makes it a unique one. Further double talon cusps were noticed in the
palatal aspect of maxillary central incisors.
PMID- 28702066
TI - Autologous platelet-rich plasma's role in enhancing the healing phase after
surgical removal of teeth.
PMID- 28702067
TI - Quantifying phenotype-environment matching in the protected Kerry spotted slug
(Mollusca: Gastropoda) using digital photography: exposure to UV radiation
determines cryptic colour morphs.
AB - BACKGROUND: Animal colours and patterns commonly play a role in reducing
detection by predators, social signalling or increasing survival in response to
some other environmental pressure. Different colour morphs can evolve within
populations exposed to different levels of predation or environmental stress and
in some cases can arise within the lifetime of an individual as the result of
phenotypic plasticity. Skin pigmentation is variable for many terrestrial slugs
(Mollusca: Gastropoda), both between and within species. The Kerry spotted slug
Geomalacus maculosus Allman, an EU protected species, exhibits two distinct
phenotypes: brown individuals occur in forested habitats whereas black animals
live in open habitats such as blanket bog. Both colour forms are spotted and each
type strongly resembles the substrate of their habitat, suggesting that G.
maculosus possesses camouflage. RESULTS: Analysis of digital images of wild slugs
demonstrated that each colour morph is strongly and positively correlated with
the colour properties of the background in each habitat but not with the
substrate of the alternative habitats, suggesting habitat-specific crypsis.
Experiments were undertaken on laboratory-reared juvenile slugs to investigate
whether ultraviolet (UV) radiation or diet could induce colour change. Exposure
to UV radiation induced the black (bog) phenotype whereas slugs reared in
darkness did not change colour. Diet had no effect on juvenile colouration.
Examination of skin tissue from specimens exposed to either UV or dark treatments
demonstrated that UV-exposed slugs had significantly higher concentrations of
black pigment in their epithelium. CONCLUSIONS: These results suggest that colour
dimorphism in G. maculosus is an example of phenotypic plasticity which is
explained by differential exposure to UV radiation. Each resulting colour morph
provides incidental camouflage against the different coloured substrate of each
habitat. This, to our knowledge, is the first documented example of colour change
in response to UV radiation in a terrestrial mollusc. Pigmentation appears to be
correlated with a number of behavioural traits in G. maculosus, and we suggest
that understanding melanisation in other terrestrial molluscs may be useful in
the study of pestiferous and invasive species. The implications of colour change
for G. maculosus conservation are also discussed.
PMID- 28702069
TI - Positive association between musclin and insulin resistance in obesity: evidence
of a human study and an animal experiment.
AB - BACKGROUND: Musclin is a novel skeletal muscle-derived secretory factor
considered to be a potent regulator of the glucose metabolism and therefore may
contribute to the pathogenesis of obesity and insulin resistance (IR). METHODS:
To test this hypothesis, we examined the plasma musclin levels in
overweight/obese subjects and lean controls. Rats on a high fat diet (HFD) were
used as the annimal model of obesity. Radioimmunoassay and western blot were used
to determine musclin levels in plasma and skeletal muscle. RESULTS: According to
radioimmunoassays,the overweight/obese subjects exhibited elevated musclin plasma
levels compared with the lean controls (89.49 +/- 19.00 ng/L vs 80.39 +/- 16.35
ng/L, P < 0.01). The musclin levels were positively correlated with triglyceride,
fasting plasma glucose, and homeostasis model assessment of IR levels. These
observations were confirmed with a high-fat diet(HFD) rat model. HFD rats also
exhibited increased musclin immunoreactivity in plasma (P < 0.01) and in skeletal
muscle (P < 0.05), as well as increased musclin mRNA levels in skeletal muscle (P
< 0.01). Musclin incubation significantly inhibited muscles 3H-2-DG uptake in the
normal diet(ND) group (P < 0.01). The protein expression of glucose transporter
type 4 was significantly down regulated by 30% (P < 0.05) in the ND group after
soleusmuscle was incubated with musclin compared with the control. Musclin
incubation also increased the protein levels of glucose-regulated protein (GRP)78
and GRP94 by 146.8 and 54% (both P < 0.05), respectively, in ND rats.
CONCLUSIONS: Our data support the hypothesis that musclin has a strong
relationship with obesity-associated IR by impairing the glucose metabolism and,
at least in part, through causing endoplasmic reticulum stress.
PMID- 28702068
TI - Hyperglycemia-induced oxidative stress and heart disease-cardioprotective effects
of rooibos flavonoids and phenylpyruvic acid-2-O-beta-D-glucoside.
AB - Diabetic patients are at an increased risk of developing heart failure when
compared to their non-diabetic counter parts. Accumulative evidence suggests
chronic hyperglycemia to be central in the development of myocardial infarction
in these patients. At present, there are limited therapies aimed at specifically
protecting the diabetic heart at risk from hyperglycemia-induced injury.
Oxidative stress, through over production of free radical species, has been
hypothesized to alter mitochondrial function and abnormally augment the activity
of the NADPH oxidase enzyme system resulting in accelerated myocardial injury
within a diabetic state. This has led to a dramatic increase in the exploration
of plant-derived materials known to possess antioxidative properties. Several
edible plants contain various natural constituents, including polyphenols that
may counteract oxidative-induced tissue damage through their modulatory effects
of intracellular signaling pathways. Rooibos, an indigenous South African plant,
well-known for its use as herbal tea, is increasingly studied for its metabolic
benefits. Prospective studies linking diet rich in polyphenols from rooibos to
reduced diabetes associated cardiovascular complications have not been
extensively assessed. Aspalathin, a flavonoid, and phenylpyruvic acid-2-O-beta-D
glucoside, a phenolic precursor, are some of the major compounds found in rooibos
that can ameliorate hyperglycemia-induced cardiomyocyte damage in vitro. While
the latter has demonstrated potential to protect against cell apoptosis, the
proposed mechanism of action of aspalathin is linked to its capacity to enhance
the expression of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) expression,
an intracellular antioxidant response element. Thus, here we review literature on
the potential cardioprotective properties of flavonoids and a phenylpropenoic
acid found in rooibos against diabetes-induced oxidative injury.
PMID- 28702070
TI - Leveling and abuse among patients with bipolar disorder at psychiatric outpatient
departments in Ethiopia.
AB - INTRODUCTION: The World Health Organization (WHO) clearly states the importance
of psychological well-being in the definition of health as "a state of complete
physical, mental and social well-being and not merely the absence of disease or
infirmity". However, in the community, the lives of people with bipolar disorders
are often harsh and abusive. Till now, the rate and related information
concerning verbal or physical abuse among patients with bipolar disorder at
psychiatric outpatient clinics have not been well addressed in Ethiopian
settings. METHODS: Data were collected by interviewing 411 systematically
selected participants at outpatient department of Amanuel Mental Specialized
Hospital. For analysis, logistic regression and adjusted odds ratios (AOR) with
95% confidence intervals (CI) were used, and P < 0.05 was considered
statistically significant. RESULTS: The prevalence of abuse (verbal/physical) was
37.7%. Having two or more episodes [AOR 1.70, 95% CI (1.06, 2.74)], a history of
aggression [AOR 3.06, 95% CI (1.63, 5.75)] and comorbid illness [AOR 2.21, 95% CI
(1.25, 3.90)] were significantly associated. CONCLUSION: The prevalence of
reported abuse is high among patients with bipolar disorder, and it is important
to remember the rights of patients during treatment.
PMID- 28702071
TI - Exclusive breastfeeding and associated factors among mothers in Gozamin district,
northwest Ethiopia: a community based cross-sectional study.
AB - BACKGROUND: Exclusive breastfeeding is defined as feeding infants only breast
milk, be it directly from breast or expressed, except drops or syrups consisting
of vitamins, mineral supplements or medicine. Exclusive breastfeeding is one of
the essential actions for infant development and survival. However, the
prevalence of exclusive breastfeeding in Ethiopia has been estimated at 52% which
is far less than the World Health Organization (WHO) recommendations. Moreover,
there are inconsistencies among estimates in different districts of the country.
Therefore, this study aimed to assess the prevalence and associated factors of
exclusive breastfeeding among mothers in Gozamin district, northwest Ethiopia.
METHODS: Using the simple random sampling technique, seven kebeles (lowest
administrative units) were selected as the primary sampling unit of the district.
Sample mother-infant pairs were then selected using the systematic random
sampling technique that involved our moving from house to house in each village.
Data were collected from 506 mother-infant pairs using interviews. Factors
associated with exclusive breastfeeding were determined using logistic
regression. The measure of association used was the odds ratio, and statistical
tests with p-values of less than 0.05 were considered as statistically
significant. RESULTS: In this study, the prevalence of exclusive breastfeeding
among mothers was 74.1% (95% CI 70.80, 79.10). For government employee mothers,
the odds of exclusive breastfeeding were reduced by half compared to housewives
(AOR 0.49, 95% CI 0.26, 0.94). Mothers who did not receive breastfeeding
counseling after delivery were 0.43 times less likely to practice exclusive
breastfeeding compared with mothers who received the services (AOR 0.43, 95% CI
0.25, 0.72). Mothers who gave birth at health institutions were more likely to
practice exclusive breastfeeding. CONCLUSION: Even though the estimated
prevalence is relatively high, more effort to meet WHO recommendations is still
necessary. Therefore, we suggest health institutions encourage hospital birthing
and increase breastfeeding counseling after delivery, and employers needs to give
longer maternity leave to improve exclusive breastfeeding practice.
PMID- 28702072
TI - Development of a phenotyping platform for high throughput screening of nodal root
angle in sorghum.
AB - BACKGROUND: In sorghum, the growth angle of nodal roots is a major component of
root system architecture. It strongly influences the spatial distribution of
roots of mature plants in the soil profile, which can impact drought adaptation.
However, selection for nodal root angle in sorghum breeding programs has been
restricted by the absence of a suitable high throughput phenotyping platform. The
aim of this study was to develop a phenotyping platform for the rapid, non
destructive and digital measurement of nodal root angle of sorghum at the
seedling stage. RESULTS: The phenotyping platform comprises of 500 soil filled
root chambers (50 * 45 * 0.3 cm in size), made of transparent perspex sheets that
were placed in metal tubs and covered with polycarbonate sheets. Around 3 weeks
after sowing, once the first flush of nodal roots was visible, roots were imaged
in situ using an imaging box that included two digital cameras that were remotely
controlled by two android tablets. Free software (openGelPhoto.tcl) allowed
precise measurement of nodal root angle from the digital images. The reliability
and efficiency of the platform was evaluated by screening a large nested
association mapping population of sorghum and a set of hybrids in six independent
experimental runs that included up to 500 plants each. The platform revealed
extensive genetic variation and high heritability (repeatability) for nodal root
angle. High genetic correlations and consistent ranking of genotypes across
experimental runs confirmed the reproducibility of the platform. CONCLUSION: This
low cost, high throughput root phenotyping platform requires no sophisticated
equipment, is adaptable to most glasshouse environments and is well suited to
dissect the genetic control of nodal root angle of sorghum. The platform is
suitable for use in sorghum breeding programs aiming to improve drought
adaptation through root system architecture manipulation.
PMID- 28702073
TI - Mathematical Simulation of Transport Kinetics of Tumor-Imaging
Radiopharmaceutical 99mTc-MIBI.
AB - The proposed model describes in a quality way the process of tumor-imaging
radiopharmaceutical 99mTc-MIBI distribution with taking into account
radiopharmaceutical accumulation, elimination, and radioactive decay. The
dependencies of concentration versus the time are analyzed. The model can be
easily tested by the concentration data of the radioactive pharmaceuticals in the
blood measured at early time point and late time point of the scanning, and the
obtained data can be used for determination of the washout rate coefficient which
is one of the existing oncology diagnostics methods.
PMID- 28702074
TI - An Exercise Health Simulation Method Based on Integrated Human
Thermophysiological Model.
AB - Research of healthy exercise has garnered a keen research for the past few years.
It is known that participation in a regular exercise program can help improve
various aspects of cardiovascular function and reduce the risk of suffering from
illness. But some exercise accidents like dehydration, exertional heatstroke, and
even sudden death need to be brought to attention. If these exercise accidents
can be analyzed and predicted before they happened, it will be beneficial to
alleviate or avoid disease or mortality. To achieve this objective, an exercise
health simulation approach is proposed, in which an integrated human
thermophysiological model consisting of human thermal regulation model and a
nonlinear heart rate regulation model is reported. The human thermoregulatory
mechanism as well as the heart rate response mechanism during exercise can be
simulated. On the basis of the simulated physiological indicators, a fuzzy finite
state machine is constructed to obtain the possible health transition sequence
and predict the exercise health status. The experiment results show that our
integrated exercise thermophysiological model can numerically simulate the
thermal and physiological processes of the human body during exercise and the
predicted exercise health transition sequence from finite state machine can be
used in healthcare.
PMID- 28702075
TI - A graph extension of the positional Burrows-Wheeler transform and its
applications.
AB - We present a generalization of the positional Burrows-Wheeler transform, or PBWT,
to genome graphs, which we call the gPBWT. A genome graph is a collapsed
representation of a set of genomes described as a graph. In a genome graph, a
haplotype corresponds to a restricted form of walk. The gPBWT is a compressible
representation of a set of these graph-encoded haplotypes that allows for
efficient subhaplotype match queries. We give efficient algorithms for gPBWT
construction and query operations. As a demonstration, we use the gPBWT to
quickly count the number of haplotypes consistent with random walks in a genome
graph, and with the paths taken by mapped reads; results suggest that haplotype
consistency information can be practically incorporated into graph-based read
mappers. We estimate that with the gPBWT of the order of 100,000 diploid genomes,
including all forms structural variation, could be stored and made searchable for
haplotype queries using a single large compute node.
PMID- 28702077
TI - A research on syndrome element differentiation based on phenomenology and
mathematical method.
AB - BACKGROUND: As an empirical medical system independent of conventional Western
medicine (CWM), over thousands of years, traditional Chinese medicine (TCM) has
established its own unique method of diagnosis and treatment. The perspective of
holism and system in TCM is essentially different from the view of Reductionism
in CWM. With the development of modern science and technology, the restriction of
reductionism is more and more prominent, and researchers begin to pay more
attention to holistic thinking in TCM. Confronted with the above situation, there
is an urgent need to explore the diagnosis of TCM by the techniques of modern
science. METHODS: To explore the feasibility of using modern science to describe
and realize the diagnosis of TCM, in this paper, a method of syndrome element
differentiation based on phenomenology is proposed. The proposed method is
implemented by mathematical mapping, and then it is testified through analysis of
670 medical records: Based on the original mapping data between two data sets
(set of syndrome elements and set of clinical manifestations), new mapping data
is generated, and thus the corresponding quantitative diagnostic results are
calculated and evaluated. Finally, knowledge discovery of the diagnosis results
based on attribute partial-ordered structure diagram is conducted. RESULTS: The
value order's matching results between original and new results show that the
matched degree of each record is no less than 65%, while there are at least 87%
records whose matched degree is more than 80%. In addition, the knowledge
discoveries of new results are basically identical with the ones of original
results as well. CONCLUSION: Using phenomenology to describe syndrome
differentiation should be feasible, and further research on mapping relations
between various sets (symptoms, formulas, drugs) of TCM should be conducted and
evaluated through clinical trials in future.
PMID- 28702078
TI - Anticancer activities and mechanisms of heat-clearing and detoxicating
traditional Chinese herbal medicine.
AB - In traditional Chinese medicine (TCM) theory, pathogenic heat and toxins, which
are akin to the inflammatory factors, are the causes of cancer and could promote
its virulent development. Therefore, heat-clearing and detoxicating (HCD) herbs
are essential components of TCM formulas for cancer treatment. An increasing
interest has been focused on the study of HCD herbs and accumulated evidences
have shown that HCD herbs or HCD herbs-based formulas exhibited remarkable
anticancer effects when used alone or combined with other therapeutic approaches.
Some of the HCD herb-derived products have been tested in clinical trials.
Studies revealed that extracts or pure compounds of the HCD herbs showed a broad
anticancer spectrum against both solid and hematologic malignancies without
significant toxic effects. Notably, some HCD herbs or formulas could strongly
enhance the anticancer activities of chemo- or radio-therapy and alleviate their
side effects. The anticancer activities of HCD herb exacts or the pure compounds
were reported to be through multiple cellular or molecular mechanisms, such as
induction of cancer cell apoptosis, differentiation and cell cycle arrest,
inhibition of cancer cell growth, invasion and metastasis, and inhibition of
tumor angiogenesis. In this review, we provide comprehensive analysis and summary
of research progress and future prospects in this field to facilitate the further
study and application of HCD herbs.
PMID- 28702079
TI - Rare bacterial isolates causing bloodstream infections in Ethiopian patients with
cancer.
AB - BACKGROUND: In recent years, saprophytic bacteria have been emerging as potential
human pathogens causing life-threatening infections in patients with
malignancies. However, evidence is lacking concerning such bacteria, particularly
in sub-Saharan countries. This study was designed to determine the spectrum and
drug resistance profile of the rare bacterial pathogens causing bloodstream
infections (BSIs) in febrile cancer patients at a referral hospital in Ethiopia.
METHODS: Between December 2011 and June 2012, blood samples were collected from
107 patients with cancer in Tikur Anbessa hospital. Culturing was performed using
the blood culture bottles and solid media and the microorganisms were identified
using the gram staining and APINE identification kits (Biomerieux, France). The
disk diffusion method was used for the antimicrobial susceptibility testing.
RESULTS: Overall, 13 (12.2%) rare human pathogens were isolated from 107 adult
febrile cancer patients investigated. Aeromonas hydrophilia species (a
fermentative gram-negative rod) was the predominant isolate, 30.8% (4/13),
followed by Chryseomonas luteola 15.4% (2/13), Sphignomonas poucimobilis 15.4%
(2/13), and Pseudomonas fluorescens 15.4% (2/13). Of the nine isolates tested for
a nine set of antibiotics, 89% were resistant to amoxicillin-clavulanic acid,
ampicillin, and trimethoprim-sulphamethoxazole. CONCLUSIONS: This study revealed
the emergence of saprophytic bacteria as potential drug-resistant nosocomial
pathogens in Ethiopian patients with cancer. As these pathogens are ubiquitous in
the environment, infection prevention actions should be strengthened in the
hospital and early diagnosis and treatment with appropriate antibiotics are
warranted for those already infected.
PMID- 28702076
TI - The management of intra-abdominal infections from a global perspective: 2017 WSES
guidelines for management of intra-abdominal infections.
AB - Intra-abdominal infections (IAIs) are common surgical emergencies and have been
reported as major contributors to non-trauma deaths in the emergency departments
worldwide. The cornerstones of effective treatment of IAIs are early recognition,
adequate source control, and appropriate antimicrobial therapy. Prompt
resuscitation of patients with ongoing sepsis is of utmost important. In
hospitals worldwide, non-acceptance of, or lack of access to, accessible evidence
based practices and guidelines result in overall poorer outcome of patients
suffering IAIs. The aim of this paper is to promote global standards of care in
IAIs and update the 2013 WSES guidelines for management of intra-abdominal
infections.
PMID- 28702080
TI - Investigation of poly(gamma-glutamic acid) production via online determination of
viscosity and oxygen transfer rate in shake flasks.
AB - BACKGROUND: Poly(gamma-glutamic acid) (gamma-PGA) is a biopolymer with many
useful properties making it applicable for instance in food and skin care
industries, in wastewater treatment, in biodegradable plastics or in the
pharmaceutical industry. gamma-PGA is usually produced microbially by different
Bacillus spp. The produced gamma-PGA increases the viscosity of the fermentation
broth. In case of shake flask fermentations, this results in an increase of the
volumetric power input. The power input in shake flasks can be determined by
measuring the torque of an orbitally rotating lab shaker. The online measurement
of the volumetric power input enables to continuously monitor the formation or
degradation of viscous products like gamma-PGA. Combined with the online
measurement of the oxygen transfer rate (OTR), the respiration activity of the
organisms can be observed at the same time. RESULTS: Two different Bacillus
licheniformis strains and three medium compositions were investigated using
online volumetric power input and OTR measurements as well as thorough offline
analysis. The online volumetric power input measurement clearly depicted changes
in gamma-PGA formation due to different medium compositions as well as
differences in the production behavior of the two investigated strains. A higher
citric acid concentration and the addition of trace elements to the standard
medium showed a positive influence on gamma-PGA production. The online power
input signal was used to derive an online viscosity signal which was validated
with offline determined viscosity values. The online measurement of the OTR
proved to be a valuable tool to follow the respiration activity of the cultivated
strains and to determine its reproducibility under different cultivation
conditions. CONCLUSIONS: The combination of the volumetric power input and the
OTR allows for an easy and reliable investigation of new strains, cultivation
conditions and medium compositions for their potential in gamma-PGA production.
The power input signal and the derived online viscosity directly reflect changes
in gamma-PGA molecular weight and concentration, respectively, due to different
cultivation conditions or production strains.
PMID- 28702081
TI - Limitation of cellulose accessibility and unproductive binding of cellulases by
pretreated sugarcane bagasse lignin.
AB - BACKGROUND: The effectiveness of the enzymatic hydrolysis of cellulose in plant
cell wall is strongly influenced by the access of enzymes to cellulose, which is
at least in part limited by the presence of lignin. Although physicochemical
treatments preceding the enzymatic catalysis significantly overcome this
recalcitrance, the residual lignin can still play a role in the process. Lignin
is suggested to act as a barrier, hindering cellulose and limiting the access of
the enzymes. It can also unspecifically bind cellulases, reducing the amount of
enzymes available to act on cellulose. However, the limiting role of the lignin
present in pretreated sugarcane bagasses has not been fully understood yet.
RESULTS: A set of sugarcane bagasses pretreated by five leading pretreatment
technologies was created and used to assess their accessibility and the
unproductive binding capacity of the resulting lignins. Steam explosion and
alkaline sulfite pretreatments resulted in more accessible substrates, with
approximately 90% of the cellulose hydrolyzed using high enzyme loadings.
Enzymatic hydrolysis of alkaline-treated (NaOH) and steam-exploded sugarcane
bagasses were strongly affected by unproductive binding at the lowest enzyme
loading tested. Analysis of the extracted lignins confirmed the superior binding
capacity of these lignins. Sulfite-based pretreatments (alkaline sulfite and acid
sulfite) resulted in lignins with lower binding capacities compared to the
analogue pretreatments without sulfite (alkaline and acidic). Strong acid groups
present in sulfite-based pretreated substrates, attributed to sulfonated lignins,
corroborated the lower binding capacities of the lignin present in these
substrates. A more advanced enzyme preparation (Cellic CTec3) was shown to be
less affected by unproductive binding at low enzyme loading. CONCLUSIONS:
Pretreatments that increase the accessibility and modify the lignin are necessary
in order to decrease the protein binding capacity. The search for the called weak
lignin-binding enzymes is of major importance if hydrolysis with low enzyme
loadings is the goal for economically viable processes.
PMID- 28702082
TI - Enzymatic degradation of sulfite-pulped softwoods and the role of LPMOs.
AB - BACKGROUND: Recent advances in the development of enzyme cocktails for
degradation of lignocellulosic biomass, especially the discovery of lytic
polysaccharide monooxygenases (LPMOs), have opened new perspectives for process
design and optimization. Softwood biomass is an abundant resource in many parts
of the world, including Scandinavia, but efficient pretreatment and subsequent
enzymatic hydrolysis of softwoods are challenging. Sulfite pulping-based
pretreatments, such as in the BALITM process, yield substrates that are
relatively easy to degrade. We have assessed how process conditions affect the
efficiency of modern cellulase preparations in processing of such substrates.
RESULTS: We show that efficient degradation of sulfite-pulped softwoods with
modern, LPMO-containing cellulase preparations requires the use of conditions
that promote LPMO activity, notably the presence of molecular oxygen and
sufficient reducing power. Under LPMO activity-promoting conditions, glucan
conversion after 48-h incubation with Cellic(r) CTec3 reached 73.7 and 84.3% for
Norway spruce and loblolly pine, respectively, at an enzyme loading of 8 mg/g of
glucan. The presence of free sulfite ions had a negative effect on hydrolysis
efficiency. Lignosulfonates, produced from lignin during sulfite pretreatment,
showed a potential to activate LPMOs. Spiking of Celluclast(r), a cellulase
cocktail with low LPMO activity, with monocomponent cellulases or an LPMO showed
that the addition of the LPMO was clearly more beneficial than the addition of
any classical cellulase. Addition of the LPMO in reactions with spruce increased
the saccharification yield from approximately 60% to the levels obtained with
Cellic(r) CTec3. CONCLUSIONS: In this study, we have demonstrated the importance
of LPMOs for efficient enzymatic degradation of sulfite-pulped softwood. We have
also shown that to exploit the full potential of LPMO-rich cellulase
preparations, conditions promoting LPMO activity, in particular the presence of
oxygen and reducing equivalents are necessary, as is removal of residual sulfite
from the pretreatment step. The use of lignosulfonates as reductants may reduce
the costs related to the addition of small molecule reductants in sulfite
pretreatment-based biorefineries.
PMID- 28702083
TI - Metabolic engineering of Rhodopseudomonas palustris for the obligate reduction of
n-butyrate to n-butanol.
AB - BACKGROUND: Rhodopseudomonas palustris is a versatile microbe that encounters an
innate redox imbalance while growing photoheterotrophically with reduced
substrates. The resulting excess in reducing equivalents, together with ATP from
photosynthesis, could be utilized to drive a wide range of bioconversions. The
objective of this study was to genetically modify R. palustris to provide a
pathway to reduce n-butyrate into n-butanol for maintaining redox balance.
RESULTS: Here, we constructed and expressed a plasmid-based pathway for n-butanol
production from Clostridium acetobutylicum ATCC 824 in R. palustris. We
maintained the environmental conditions in such a way that this pathway
functioned as the obligate route to re-oxidize excess reducing equivalents,
resulting in an innate selection pressure. The engineered strain of R. palustris
grew under otherwise restrictive redox conditions and achieved concentrations of
1.5 mM n-butanol at a production rate of 0.03 g L-1 day-1 and a selectivity
(i.e., products compared to the consumed substrate) of close to 40%. Since the
theoretical maximum selectivity is 45%, the engineered strain converted close to
its maximum selectivity. CONCLUSIONS: The innate redox imbalance of R. palustris
can be used to drive the reduction of n-butyrate into n-butanol after expression
of a plasmid-based enzyme from a butanol-producing Clostridium strain.
PMID- 28702084
TI - Modification of the nanostructure of lignocellulose cell walls via a non
enzymatic lignocellulose deconstruction system in brown rot wood-decay fungi.
AB - Wood decayed by brown rot fungi and wood treated with the chelator-mediated
Fenton (CMF) reaction, either alone or together with a cellulose enzyme cocktail,
was analyzed by small angle neutron scattering (SANS), sum frequency generation
(SFG) spectroscopy, Fourier transform infrared (FTIR) analysis, X-ray diffraction
(XRD), atomic force microscopy (AFM), and transmission electron microscopy (TEM).
Results showed that the CMF mechanism mimicked brown rot fungal attack for both
holocellulose and lignin components of the wood. Crystalline cellulose and lignin
were both depolymerized by the CMF reaction. Porosity of the softwood cell wall
did not increase during CMF treatment, enzymes secreted by the fungi did not
penetrate the decayed wood. The enzymes in the cellulose cocktail also did not
appear to alter the effects of the CMF-treated wood relative to enhancing cell
wall deconstruction. This suggests a rethinking of current brown rot decay models
and supports a model where monomeric sugars and oligosaccharides diffuse from the
softwood cell walls during non-enzymatic action. In this regard, the CMF
mechanism should not be thought of as a "pretreatment" used to permit enzymatic
penetration into softwood cell walls, but instead it enhances polysaccharide
components diffusing to fungal enzymes located in wood cell lumen environments
during decay. SANS and other data are consistent with a model for
repolymerization and aggregation of at least some portion of the lignin within
the cell wall, and this is supported by AFM and TEM data. The data suggest that
new approaches for conversion of wood substrates to platform chemicals in
biorefineries could be achieved using the CMF mechanism with >75% solubilization
of lignocellulose, but that a more selective suite of enzymes and other
downstream treatments may be required to work when using CMF deconstruction
technology. Strategies to enhance polysaccharide release from lignocellulose
substrates for enhanced enzymatic action and fermentation of the released
fraction would also aid in the efficient recovery of the more uniform modified
lignin fraction that the CMF reaction generates to enhance biorefinery
profitability.
PMID- 28702085
TI - Electricity-assisted production of caproic acid from grass.
AB - BACKGROUND: Medium chain carboxylic acids, such as caproic acid, are
conventionally produced from food materials. Caproic acid can be produced through
fermentation by the reverse beta-oxidation of lactic acid, generated from low
value lignocellulosic biomass. In situ extraction of caproic acid can be achieved
by membrane electrolysis coupled to the fermentation process, allowing recovery
by phase separation. RESULTS: Grass was fermented to lactic acid in a leach-bed
type reactor, which was then further converted to caproic acid in a secondary
fermenter. The lactic acid concentration was 9.36 +/- 0.95 g L-1 over a 33-day
semi-continuous operation, and converted to caproic acid at pH 5.5-6.2, with a
concentration of 4.09 +/- 0.54 g L-1 during stable production. The caproic acid
product stream was extracted in its anionic form, concentrated and converted to
caproic acid by membrane electrolysis, resulting in a >70 wt% purity solution. In
a parallel test exploring the upper limits of production rate through cell
retention, we achieved the highest reported caproic acid production rate to date
from a lignocellulosic biomass (grass, via a coupled process), at 0.99 +/- 0.02 g
L-1 h-1. The fermenting microbiome (mainly consisting of Clostridium IV and
Lactobacillus) was capable of producing a maximum caproic acid concentration of
10.92 +/- 0.62 g L-1 at pH 5.5, at the border of maximum solubility of protonated
caproic acid. CONCLUSIONS: Grass can be utilized as a substrate to produce
caproic acid. The biological intermediary steps were enhanced by separating the
steps to focus on the lactic acid intermediary. Notably, the pipeline was almost
completely powered through electrical inputs, and thus could potentially be
driven from sustainable energy without need for chemical input.Graphical
abstractMicrobial and electrochemical production of lactic acid, caproic acid and
decane from grass.
PMID- 28702086
TI - Transcriptome and key genes expression related to carbon fixation pathways in
Chlorella PY-ZU1 cells and their growth under high concentrations of CO2.
AB - BACKGROUND: The biomass yield of Chlorella PY-ZU1 drastically increased when
cultivated under high CO2 condition compared with that cultivated under air
condition. However, less attention has been given to the microalgae
photosynthetic mechanisms response to different CO2 concentrations. The genetic
reasons for the higher growth rate, CO2 fixation rate, and photosynthetic
efficiency of microalgal cells under higher CO2 concentration have not been
clearly defined yet. RESULTS: In this study, the Illumina sequencing and de novo
transcriptome assembly of Chlorella PY-ZU1 cells cultivated under 15% CO2 were
performed and compared with those of cells grown under air. It was found that
carbonic anhydrase (CAs, enzyme for interconversion of bicarbonate to CO2)
dramatically decreased to near 0 in 15% CO2-grown cells, which indicated that CO2
molecules directly permeated into cells under high CO2 stress without CO2
concentrating mechanism. Extrapolating from the growth conditions and
quantitative Real-Time PCR of CCM-related genes, the Km (CO2) (the minimum
intracellular CO2 concentration that rubisco required) of Chlorella PY-ZU1 might
be in the range of 80-192 MUM. More adenosine triphosphates was saved for carbon
fixation-related pathways. The transcript abundance of rubisco (the most
important enzyme of CO2 fixation reaction) was 16.3 times higher in 15% CO2-grown
cells than that under air. Besides, the transcript abundances of most key genes
involved in carbon fixation pathways were also enhanced in 15% CO2-grown cells.
CONCLUSIONS: Carbon fixation and nitrogen metabolism are the two most important
metabolisms in the photosynthetic cells. These genes related to the two most
metabolisms with significantly differential expressions were beneficial for
microalgal growth (2.85 g L-1) under 15% CO2 concentration. Considering the micro
and macro growth phenomena of Chlorella PY-ZU1 under different concentrations of
CO2 (0.04-60%), CO2 transport pathways responses to different CO2 (0.04-60%)
concentrations was reconstructed.
PMID- 28702087
TI - Comparison of ethanol production from corn cobs and switchgrass following a
pyrolysis-based biorefinery approach.
AB - BACKGROUND: One of the main obstacles in lignocellulosic ethanol production is
the necessity of pretreatment and fractionation of the biomass feedstocks to
produce sufficiently pure fermentable carbohydrates. In addition, the by-products
(hemicellulose and lignin fraction) are of low value, when compared to dried
distillers grains (DDG), the main by-product of corn ethanol. Fast pyrolysis is
an alternative thermal conversion technology for processing biomass. It has
recently been optimized to produce a stream rich in levoglucosan, a fermentable
glucose precursor for biofuel production. Additional product streams might be of
value to the petrochemical industry. However, biomass heterogeneity is known to
impact the composition of pyrolytic product streams, as a complex mixture of
aromatic compounds is recovered with the sugars, interfering with subsequent
fermentation. The present study investigates the feasibility of fast pyrolysis to
produce fermentable pyrolytic glucose from two abundant lignocellulosic biomass
sources in Ontario, switchgrass (potential energy crop) and corn cobs (by-product
of corn industry). RESULTS: Demineralization of biomass removes catalytic centers
and increases the levoglucosan yield during pyrolysis. The ash content of biomass
was significantly decreased by 82-90% in corn cobs when demineralized with acetic
or nitric acid, respectively. In switchgrass, a reduction of only 50% for both
acids could be achieved. Conversely, levoglucosan production increased 9- and 14
fold in corn cobs when rinsed with acetic and nitric acid, respectively, and
increased 11-fold in switchgrass regardless of the acid used. After pyrolysis,
different configurations for upgrading the pyrolytic sugars were assessed and the
presence of potentially inhibitory compounds was approximated at each step as
double integral of the UV spectrum signal of an HPLC assay. The results showed
that water extraction followed by acid hydrolysis and solvent extraction was the
best upgrading strategy. Ethanol yields achieved based on initial cellulose
fraction were 27.8% in switchgrass and 27.0% in corn cobs. CONCLUSIONS: This
study demonstrates that ethanol production from switchgrass and corn cobs is
possible following a combined thermochemical and fermentative biorefinery
approach, with ethanol yields comparable to results in conventional pretreatments
and fermentation processes. The feedstock-independent fermentation ability can
easily be assessed with a simple assay.
PMID- 28702088
TI - Delayed recognition of an ipsilateral femoral neck and shaft fracture leading to
preventable subsequent complications: a case report.
AB - BACKGROUND: Ipsilateral femoral shaft and neck fractures are rare injuries,
affecting mostly young patients who sustained high-energy traumas. In 19-50% of
cases, the femoral fracture is misdiagnosed or overlooked at the initial
presentation, with reportedly increased risk of complications such as non-union
and avascular necrosis. We present a case of an ipsilateral femoral neck and
shaft fracture, which was missed at initial presentation despite radiographic and
computed tomography (CT) scan evaluation. CASE PRESENTATION: A 56-year old female
was admitted to our institution following a high-energy trauma (fall from 6 m).
Initial radiographic and CT scan evaluation revealed a displaced femoral shaft
fracture but no other femoral fractures were detected. Closed reduction and
external fixation of the femoral shaft fracture was performed in the emergency
setting. Follow-up radiologic evaluations revealed an ipsilateral laterally
displaced femoral neck fracture. Despite cephalomedullary nail fixation of both
fractures performed on the third day from the initial injury, the patient
developed a non-union of the femoral neck fracture, which led to cut-out of the
lag screw with associated varus failure of the femoral neck fracture requiring
surgical revision and implant of a bipolar hemiarthroplasty at one year follow
up. The postoperative course was uneventful and the patient had a full long-term
recovery. CONCLUSION: This case report exemplifies the need to maintain the
highest level of suspiciousness for the concomitant presence of an ipsilateral
femoral neck fracture when treating polytraumatized patients who sustained a
femoral shaft fracture as a consequence of a high-energy trauma. Furthermore, the
pre-operative standardized radiological evaluation (plain x-ray and CT scan)
might not always help in ruling out these fractures. It is therefore necessary to
adopt additional standardized radiographic protocols not only in the pre
operative but also in the intra-operative and immediate post-operative settings.
PMID- 28702089
TI - Diabetes educator role boundaries in Australia: a documentary analysis.
AB - BACKGROUND: Diabetes educators provide self-management education for people
living with diabetes to promote optimal health and wellbeing. Their national
association is the Australian Diabetes Educators Association (ADEA), established
in 1981. In Australia the diabetes educator workforce is a diverse,
interdisciplinary entity, with nurses, podiatrists, dietitians and several other
health professional groups recognised by ADEA as providers of diabetes education.
Historically nurses have filled the diabetes educator role and anecdotally,
nurses are perceived to have wider scope of practice when undertaking the
diabetes educator role than the other professions eligible to practise diabetes
education. The nature of the interprofessional role boundaries and differing
scopes of practice of diabetes educators of various primary disciplines are
poorly understood. Informed by a documentary analysis, this historical review
explores the interprofessional evolution of the diabetes educator workforce in
Australia and describes the major drivers shaping the role boundaries of diabetes
educators from 1981 until 2017. METHODS: This documentary analysis was undertaken
in the form of a literature review. STARLITE framework guided the searches for
grey and peer reviewed literature. A timeline featuring the key events and
changes in the diabetes educator workforce was developed. The timeline was
analysed and emerging themes were identified as the major drivers of change
within this faction of the health workforce. RESULTS: This historical review
illustrates that there have been drivers at the macro, meso and micro levels
which reflect and are reflected by the interprofessional role boundaries in the
diabetes educator workforce. The most influential drivers of the
interprofessional evolution of the diabetes educator workforce occurred at the
macro level and can be broadly categorised according to three major influences:
the advent of non-medical prescribing; the expansion of the Medicare Benefits
Schedule to include rebates for allied health services; and the competency
movement. CONCLUSION: This analysis illustrates the gradual movement of the
diabetes educator workforce from a nursing dominant entity, with an emphasis on
interprofessional role boundaries, to an interdisciplinary body, in which role
flexibility is encouraged. There is however, recent evidence of role boundary
delineation at the meso and micro levels.
PMID- 28702090
TI - Translation and validation of diabetes self-management profile (DSMP) into
Brazilian Portuguese language: first instrument to assess type 1 diabetes self
management in a pediatric population.
AB - OBJECTIVE: To translate and validate the instrument Diabetes Self-Management
Profile (DSMP)-Conventional and Flexible Regimens into Brazilian Portuguese
language in order to evaluate the quality of diabetes self-management in children
and adolescents with type 1 diabetes and their caregivers. METHODS: DSMP was
submitted to forward and back translation method and validated in a group of type
1 diabetes youths between 6 and 18 years (n = 102), and their families. Analysis
of DSMP internal consistency, intra and interobserver reliability and concurrent
correlation with HbA1c were done. RESULTS: DSMP total scores demonstrated
adequate internal consistency (Cronbach's alpha = 0.79), 3-month test-retest
reliability (rho = 0.53; p < 0.001), inter-interviewer agreement (rho = 0.55; p <
0.001). DSMP total score was significantly correlated to HbA1c (rho = -0.54, p <
0.001). CONCLUSION: DSMP-translated version is a reliable and valid tool to
assess diabetes self-management.
PMID- 28702091
TI - Educ@dom: comparative study of the telemonitoring of patients with type 2
diabetes versus standard monitoring-study protocol for a randomized controlled
study.
AB - BACKGROUND: The global prevalence of type 2 diabetes is considerable. To avoid or
delay its chronic complications, patients with type 2 diabetes should improve
blood glucose management by adapting their life style. This involves changing the
way in which diabetes is controlled. We believe that, thanks to technological
innovations in connected health-monitoring devices, the telemonitoring of type 2
diabetes patients using therapeutic educational tools is likely to help them
adapt their treatment and lifestyle habits, and therefore improve blood glucose
management. METHODS: This is a multicenter, randomized, controlled, prospective
study. The primary objective is to compare the efficacy of telemonitoring to
standard monitoring in terms of changes in glycated hemoglobin levels (HbA1c)
after a 1 year follow-up period. The secondary objectives are clinical (changes
in knowledge, physical activity, weight, etc.) and medical-economic. 282 patients
are required (141 patients in each group) to satisfy the primary objective. For
patients in the intervention group, the device will be given to them for 1 year
and then withdrawn during the second year of follow-up. CONCLUSIONS: The
anticipated benefits of this research are an improvement in blood glucose
management in patients with type 2 diabetes by improving their lifestyle whilst
rationalizing recourse to consultations in order to reduce the incidence of
complications and cost in the long term. If the results of this study show that
management of type 2 diabetes by tele monitoring is clinically effective and
economical, this device could then be made available to a larger diabetic patient
cohort.
PMID- 28702092
TI - PAT-H-MS coupled with laser microdissection to study histone post-translational
modifications in selected cell populations from pathology samples.
AB - BACKGROUND: Aberrations in histone post-translational modifications (hPTMs) have
been linked with various pathologies, including cancer, and could not only
represent useful biomarkers but also suggest possible targetable epigenetic
mechanisms. We have recently developed an approach, termed pathology tissue
analysis of histones by mass spectrometry (PAT-H-MS), that allows performing a
comprehensive and quantitative analysis of histone PTMs from formalin-fixed
paraffin-embedded pathology samples. Despite its great potential, the application
of this technique is limited by tissue heterogeneity. METHODS: In this study, we
further implemented the PAT-H-MS approach by coupling it with techniques aimed at
reducing sample heterogeneity and selecting specific portions or cell populations
within the samples, such as manual macrodissection and laser microdissection
(LMD). RESULTS: When applied to the analysis of a small set of breast cancer
samples, LMD-PAT-H-MS allowed detecting more marked changes between luminal A
like and triple negative patients as compared with the classical approach. These
changes included not only the already known H3 K27me3 and K9me3 marks, but also
H3 K36me1, which was found increased in triple negative samples and validated on
a larger cohort of patients, and could represent a potential novel marker
distinguishing breast cancer subtypes. CONCLUSIONS: These results show the
feasibility of applying techniques to reduce sample heterogeneity, including
laser microdissection, to the PAT-H-MS protocol, providing new tools in clinical
epigenetics and opening new avenues for the comprehensive analysis of histone
post-translational modifications in selected cell populations.
PMID- 28702093
TI - Human Eye Movements After Viewpoint Shifts in Edited Dynamic Scenes are Under
Cognitive Control.
AB - We tested whether viewers have cognitive control over their eye movements after
cuts in videos of real-world scenes. In the critical conditions, scene cuts
constituted panoramic view shifts: Half of the view following a cut matched the
view on the same scene before the cut. We manipulated the viewing task between
two groups of participants. The main experimental group judged whether the scene
following a cut was a continuation of the scene before the cut. Results showed
that following view shifts, fixations were determined by the task from 250 ms
until 1.5 s: Participants made more and earlier fixations on scene regions that
matched across cuts, compared to nonmatching scene regions. This was evident in
comparison to a control group of participants that performed a task that did not
require judging scene continuity across cuts, and did not show the preference for
matching scene regions. Our results illustrate that viewing intentions can have
robust and consistent effects on gaze behavior in dynamic scenes, immediately
after cuts.
PMID- 28702094
TI - Disorders of nutritional status in sepsis - facts and myths.
AB - The problem of diagnosing nutritional status disorders in septic patients remains
unresolved. This is associated with the necessity of the introduction of newer
and newer methods of assessing nutritional status, often requiring precise and
expensive equipment as well as employment of professionals in this field in
hospital wards, primarily including intensive care units (ICU). Methods that have
been applied thus far for assessing nutritional status, also used in severely ill
septic patients, have little impact on improving treatment results. This is due
to the high dynamics of changes in nutritional status in these patients, healing
process variability in individual patients, and the "mismatch" of methods for
assessing nutritional status in relation to the patient's clinical status. The
diagnostic value of the traditional methods of assessing nutritional status, i.e.
anthropometric analysis and selected laboratory tests, as markers of nutritional
status disorders in septic patients, is still debatable. There is still no
precise method that could become the "gold standard" allowing for early
identification of malnutrition in these group of patients. Phase angle,
bioelectrical impedance vector analysis (BIVA), and the "illness marker",
obtained directly from the resistance, reactance, and impedance, can be used as
prognostic or nutritional indices in severely ill septic patients, but the
intensity of research on this subject needs to be increased. Detailed assessment
of nutritional status should include tests of selected inflammation markers
(including TLC, HMGB1, IL-6, IL-10, IL-1ra, sTNFRI).
PMID- 28702095
TI - Butyric acid - a well-known molecule revisited.
AB - The properties of butyric acid, and the role it plays in the gastrointestinal
tract, have been known for many years. However, the newest research shows that
butyric acid still remains a molecule with a potential that has not as yet been
fully exploited. The article provides an outline of relevant up-to-date knowledge
about butyric acid, and presents the expert position on the clinical benefits of
using butyric acid products in the therapy of gastrointestinal diseases.
PMID- 28702096
TI - Cost-effectiveness of biological treatment of ulcerative colitis - a systematic
review.
AB - The aim of this systematic review was to collect and summarise all current data
on the cost-effectiveness of biological treatment in ulcerative colitis. A
literature search was conducted using the Medline, Embase, Centre for Reviews and
Dissemination databases and included all cost-effectiveness analyses comparing
biological treatment with any comparator. We identified 277 records of which 10
were included in this review. Eighty percent of identified analyses used quality
adjusted life years (QALY) as a measure of outcome. The most commonly assessed
biological agent was infliximab. Half of the eight economic analyses, with QALY
as an outcome, showed the cost-effectiveness of biological treatment against the
comparator. Incremental cost-effectiveness ratios (ICER) ranged from 15,748 euro
to 450,791 euro. The highest ICER values were observed when biologicals were
compared with standard care alone. This systematic review revealed that in some
cases the biological treatment, despite its clinical effectiveness, is too
expensive and exceeds the national threshold value.
PMID- 28702097
TI - Pediatric achalasia. Single-center study of interventional treatment.
AB - INTRODUCTION: Esophageal achalasia is a rare entity in children. However, young
age is a factor of failure of conservative treatment, emphasizing the role of
surgery. In our institution laparoscopic Heller's cardiomyotomy is the chosen
procedure for surgical treatment. AIM: To assess the outcome of surgery for
achalasia treatment in children operated on in a single institution. MATERIAL AND
METHODS: A retrospective analysis of consecutive patient records from the years
1997 to 2014 was performed. There were 11 patients. Their mean age was 13 years,
ranging from 6 to 17. Duration of symptoms was 2 to 36 months, mean 16. All 11
patients were operated on with a laparoscopic approach. Pneumatic dilatation was
used both pre- and postoperatively but in no case was sufficient on its own.
Collected data included patient demographics, preoperative symptoms and their
duration, diagnostic findings and therapeutic means. Surgical procedures,
complications and long-term follow-up were analyzed. The follow-up lasted from 1
to 10 years and finished when the patient reached 18 years of age. RESULTS:
Twelve laparoscopic cardiomyotomies were performed with concomitant
fundoplications, 10 Toupet and 2 Dor and one redo procedure. There were no
deaths. Two perforations were repaired promptly. The success rate was 82%, though
with subsequent dilatations. One failure was due to serious progression of the
disease. CONCLUSIONS: In our opinion, laparoscopic Heller's myotomy is the
procedure of choice for treating achalasia in children. Endoscopic balloon
dilatation may be used as a complementary treatment, especially as a primary redo
procedure.
PMID- 28702098
TI - Hepatitis B and C seroprevalence in patients with diabetes mellitus and its
relationship with microvascular complications.
AB - INTRODUCTION: Diabetic patients are susceptible to bacterial, viral and fungal
infections because of various deficiencies in the immune system. AIM: To
investigate a possible link between hepatitis B/C prevalence and microvascular
complications as well as duration of diabetes. MATERIAL AND METHODS: In total
1263 diabetic patients (1149 type 2, 114 type 1) were enrolled in the study. The
control group consisted of 1482 healthy blood donors who were over 40 years old.
All diabetic patients were tested for HBsAg, anti-HBs and anti-HCV beside routine
laboratory tests. Diabetic patients were divided into three groups according to
their diabetes duration, and all of the patients were scanned for microvascular
complications. Demographic data of all patients were recorded. RESULTS: HBsAg
seropositivity was 3.7% in diabetic patients and 1.08% in the control group; this
difference was statistically significant (p < 0.001). HBsAg positivity rates in
type 1 and type 2 diabetics were 0.8% and 4%, respectively (p = 0.09). HCV
seropositivity was 2.2% for diabetics and 0.5% for the control group; this
difference was statistically significant (p < 0.001). Anti-HCV seropositivity in
type 1 and type 2 diabetics was 1.75% and 2.26%, respectively. There was no
relationship between diabetes duration and hepatitis B-C prevalence (p > 0.05).
Also, no relationship was found between microvascular complications of diabetes
and hepatitis B/C seropositivity. CONCLUSIONS: Hepatitis B and C seroprevalence
was found to be increased in diabetes mellitus; however, there was no
relationship between hepatitis seroprevalence and the duration or microvascular
complications of diabetes.
PMID- 28702099
TI - Strategies for early metabolic disturbances in patients with an end jejunostomy
or end ileostomy. Experience from a specialized Home Parenteral Nutrition (HPN)
center.
AB - INTRODUCTION: An end stoma syndrome is usually the result of an intentional
surgical intervention in the course of staged treatment or a complication of
surgery. These patients most frequently suffer from water and electrolyte
disturbances, malnutrition syndromes caused by malabsorption of trace elements
and/or vitamins, and undernutrition. AIM: To present early metabolic disturbances
observed in patients with an end jejunostomy or end ileostomy syndrome on the
first day of their hospitalization in a specialist Home Parenteral Nutrition
(HPN) center. MATERIAL AND METHODS: The study included 142 patients with an end
stoma syndrome (76 women and 66 men), hospitalized between 2004 and 2014.
Patients were divided into two main groups. Group A consisted of 90 patients with
an end jejunostomy and group B consisted of 52 patients with an end ileostomy.
RESULTS: After comparing the patients with an end jejunostomy vs. those with an
end ileostomy, significant differences were found as regards pH (7.34 vs. 7.39, p
= 0.043) and BE (3.24 vs. -0.86, p = 0.005). Depending on the lack or possibility
of oral food intake, patients in the end jejunostomy group had different levels
of the markers phosphate, Mg, Ca, urea, and creatinine, with all of these
parameters within normal laboratory limits. When the end ileostomy group was
divided into subgroups depending on the lack or possibility of oral food intake,
differences in C-reactive protein activity were found (55.6 vs. 25.7, p = 0.041).
CONCLUSIONS: Patients with an end jejunostomy syndrome are more prone to
metabolic acidosis with significant alkali deficiencies.
PMID- 28702100
TI - Transthoracic versus transhiatal esophagectomy - influence on patient survival.
AB - AIM: To evaluate the survival of patients after surgery of the esophagus/cardia
using the transthoracic and transhiatal methods. MATERIAL AND METHODS: In the
years 2007-2011, 102 patients were radically treated for cancer of the
esophagus/cardia: 24 women and 78 men at the average age of 59.5. There were 38
transthoracic procedures and 64 transhiatal procedures. All patients had a
conduit made from the stomach, led through lodges in the esophagus and combined
with the stump of the esophagus in the neck following the Collard method. Two
pole lymphadenectomies were performed in all patients. RESULTS: Patients after
transthoracic procedures had statistically more (p < 0.05) lymph nodes removed
than patients after transhiatal procedures. The 5-year survival rates in
transhiatal and transthoracic procedures did not statistically differ, being 8%
and 0% respectively. The length of patient survival was influenced by metastases
in the nearby lymph nodes (p < 0.0001) and the presence of adenocarcinoma.
CONCLUSIONS: Surgical access (transhiatal and transthoracic surgery) does not
affect the 5-year survival rates. Transhiatal surgery allows a greater number of
lymph nodes to be removed. The main factor influencing the 5-year survival rate
is the presence of metastases in the nearby lymph nodes.
PMID- 28702101
TI - Rotavirus genotypes in children with gastroenteritis in Erzurum: first detection
of G12P[6] and G12P[8] genotypes in Turkey.
AB - INTRODUCTION: Rotavirus is one of the leading pathogens which cause acute
gastroenteritis in children and is responsible for a substantial proportion of
childhood deaths worldwide. AIM: To determine the group A rotavirus (RVA)
prevalence and genotypes of circulating RVA strains in 0-5-year-old children with
complaints of vomiting and diarrhoea in Eastern Anatolia in Turkey. MATERIAL AND
METHODS: RNA extracted from stool specimens of 329 children aged 0-5 years with
acute diarrhoea was subjected to reverse transcription polymerase reaction (RT
PCR) and multiplex-nested PCR. The genotypes were identified based on the
expected size of the amplicon, which was amplified with a genotype-specific
primer. RESULTS: Out of 329 stool samples analyzed, 109 (33.1%) were positive for
RVA. G1P[8] was the dominant genotype combination (42.2%), followed by G9P[8]
(21.1%) and G12P[6] (11.0%). Mixed infections were identified in 5 cases: G3,9 in
2 cases, G1,9 in 1 case, P[4,8] in 1 case, and P[6,8] in 1 case. The P genotype
could not be typed in two patients. CONCLUSIONS: In the study, we detected six
different rotavirus G genotypes, 3 different P genotypes, 11 different G-P
combinations and 5 different mixed genotypes combinations. G1, G9, G12 and P[8]
were found to be the predominant genotypes. G12P[6] and G12P[8] genotypes,
showing an increase as new rotavirus genotypes in the world, are reported for the
first time for our regions. We determined the dominant genotypes, mixed genotypes
and unconventional genotypes of rotavirus in our region.
PMID- 28702102
TI - Evaluation of argon plasma coagulation in healing of a solitary rectal ulcer in
comparison with conventional therapy: a randomised controlled trial.
AB - INTRODUCTION: Argon plasma coagulation (APC) has been reported to be effective in
the treatment of solitary rectal ulcer syndrome (SRUS). However, it has not
appeared to be effective in healing ulcers. AIM: This study aimed at assessing
the effectiveness of APC in controlling rectal ulcer-induced bleeding, and at
examining the ultimate effect of this approach in healing these lesions. MATERIAL
AND METHODS: This randomised, controlled trial was conducted on 99 patients with
SRUS. Patients were randomly enrolled into two groups of APC therapy
(intervention) and conventional therapy (control). The control group (n = 58)
received a high-fibre diet, laxatives, behaviour therapy, and sucralfate enemas,
and the intervention group (n = 41) were treated with APC plus conventional
therapy; in fact they received directed and focused argon gas in addition to a
high-fibre diet and laxatives. RESULTS: Responses to treatment in the control
group and in the APC-receiving group were 29.3% and 75.6%, respectively. The
continuation of ulcer healing after 3 months in the control group was 10.3%, and
it was 70.7% in the APC-treated group. There was a significant statistical
difference between the two groups (p < 0.004), i.e. bleeding was controlled more
frequently in the group receiving APC plus conventional therapies than in the
group receiving only the conventional therapies. However, the results showed no
statistically significant difference between the two groups in terms of pain
relief (p < 0.36). CONCLUSIONS: Argon plasma coagulation not only controlled
bleeding in patients with SRUS, but also, in comparison with the conventional
methods of treating SRUS, led to healing and continuation of healing of rectal
ulcers.
PMID- 28702103
TI - Current prevalence of Helicobacter pylori infection in patients with dyspepsia
treated in Warsaw, Poland.
AB - INTRODUCTION: The prevalence of Helicobacter pylori (Hp) infection in patients
with dyspepsia has important clinical and epidemiological implications. However,
the current prevalence of Hp infection among patients within Poland is unknown;
the last data were collected a decade ago and the majority of previous studies
showed the prevalence to be between 60% and 100%. AIM: To establish the current
prevalence of Hp infection among patients with dyspepsia in Warsaw, Poland.
MATERIAL AND METHODS: The study group comprised 148 patients (126 women and 22
men) with dyspepsia, treated in two outpatient clinics in Warsaw. The mean age in
the group that tested positive for Hp was 45.8 years (SD = 14.86; median = 51;
min = 19; max = 64). They were tested for Hp infection with a urea breath test
that uses 13C-enriched urea and isotope ratio mass spectrometry. RESULTS:
Helicobacter pylori infection was found in 53 patients (44 women and 9 men), i.e.
in 35.8% of the whole study group. We did not find any significant relationship
between Hp infection and the patients' age, gender, or their body mass index.
CONCLUSIONS: The current prevalence of Hp infection among patients with dyspepsia
treated in Warsaw is 35.8%. However, our data suggest almost a two-fold fall in
the prevalence of Hp infection compared to the previous Polish studies.
PMID- 28702104
TI - Immature granulocytes predict severe acute pancreatitis independently of systemic
inflammatory response syndrome.
AB - INTRODUCTION: Early prediction of severity of acute pancreatitis (AP) by a simple
parameter that positively correlates with the activation stage of the immune
system would be very helpful because it could influence the management and
improve the outcome. Tumor necrosis factor alpha (TNF-alpha) and interleukin-1
(IL-1) play a critical role in the pathogenesis systemic inflammatory response
syndrome (SIRS) and severity of AP. One of the effects of IL-1 and TNF-alpha is
an increase in the number of immature granulocytes (IGs) in the peripheral blood.
AIM: To assess whether the IGs% in plasma could be an independent marker of AP
severity. MATERIAL AND METHODS: A cohort of 77 patients with AP were
prospectively enrolled in the study. The IGs were measured from whole blood
samples obtained from the first day of hospitalization using an automated
analyser. RESULTS: We observed 44 (57%) patients with mild AP, 21 (27%) patients
with moderate severe AP (SAP) and 12 (16%) patients with SAP. The cut-off value
of IGs was 0.6%. The IGs > 0.6% had a sensitivity, specificity, and positive and
negative predictive value of 100%, 96%, 85.7%, and 100%, respectively (area under
the curve (AUC) = 0.98). On admission, SIRS was present in 25 (32%) patients. We
found that in patients who fulfilled at least two criteria for SIRS, SAP could be
predicted with 75% sensitivity and 75.4% specificity, positive predictive value
36%, negative predictive value 94.2%. CONCLUSIONS: The IGs% as a routinely
obtained marker appears to be a promising, independent biomarker and a better
predictor of early prognosis in SAP than SIRS and white blood cell.
PMID- 28702105
TI - The effect of cyclic rifaximin therapy on symptoms of diverticular disease from
the perspective of the gastroenterology outpatient clinic: a "real-life" study.
AB - INTRODUCTION: Symptomatic uncomplicated diverticular disease of the colon (SUDD)
is one of the most common diseases with which patients present to a
gastroenterologist. Mild forms of diverticulitis can also be treated using
rifaximin. Although numerous randomised controlled trials have already
demonstrated the efficacy of rifaximin therapy, there is still a lack of data
from daily medical practice. AIM: To assess the effect of rifaximin on the
symptoms of diverticular disease (SUDD and mild diverticulitis) in patients
undergoing routine treatment in gastroenterology outpatient clinics in Poland.
MATERIAL AND METHODS: The retrospective study included 142 patients with a
diagnosis of SUDD and mild diverticulitis, with a mean age of 60-69 years (41%),
of whom 65% were women. Patients underwent three cycles of rifaximin therapy at a
dose of 2 * 400 mg daily for 7 days over 3 consecutive months. Survey data were
collected during monthly clinic appointments using a questionnaire completed by
48 gastroenterologists, and in selected cases standard inflammatory parameters
were also determined. RESULTS: After just one cycle of therapy a significant
reduction in disease symptoms was observed (abdominal pain, abdominal tenderness,
bloating, disturbances in bowel habit), defined over a scale of 0-3 points. The
mean intensity of symptoms decreased from 1.7 +/-0.7 to 0.8 +/-0.3 points (with a
maximum symptom intensity of 3.0 points). After three cycles, the severity of
symptoms decreased markedly to an average of 0.3 +/-0.1, and as many as 75% of
patients reported no abdominal pain (previously the percentage was only 4%).
These differences were statistically significant, p < 0.001. The decrease in
inflammatory parameters (white blood cell count, C-reactive protein and
erythrocyte sedimentation rate) was statistically significant. CONCLUSIONS:
Rifaximin is highly effective in the symptomatic relief of uncomplicated
diverticular disease of the large bowel, and it is also effective in the
treatment of mild forms of diverticulitis. Although the effects were already
visible after the first cycle of therapy, the highest efficacy was obtained after
three cycles of therapy. Rifaximin can be successfully used in routine medical
practice.
PMID- 28702106
TI - Malignant peritoneal mesothelioma - a rare cause of laparotomy.
PMID- 28702107
TI - Acute appendicitis due to hair follicle obstruction: a rare case report.
PMID- 28702108
TI - Acute abdomen in a mentally retarded patient: cecal volvulus.
PMID- 28702109
TI - Bolstering Skin Grafts With a Surgical Scrub Brush: A Cost-effective Solution.
AB - Objective: The objective of this article is to review the methods currently used
for the bolstering of skin grafts and compare their advantages and disadvantages
with those of the dry, sterile surgical scrub brush. We report a series of cases
performed at a single institution and compare the cost-effectiveness,
application, and limitations of this method with other options for skin graft
bolstering. Methods: A PubMed search using the parameters "(bolster) AND skin
graft" was conducted, yielding 85 results. A total of 40 publications met the
criteria for our literature review. The costs of the foam bolsters utilized as
stents for skin grafts were obtained from the Central Supply and Resource
Division of the University of Louisville Hospital for a cost analysis. The cost
per square centimeter of each bolster material was calculated. Results: At
$0.003/cm2, the 3M Reston foam is the most inexpensive of the 3 bolster materials
analyzed. The dry, sterile surgical scrub brush has a similar cost at $0.006/cm2
but carries the advantage of sterility. The material cost of negative pressure
wound therapy is $0.47/cm2, and the cost of the system as a whole makes it a much
more expensive alternative. In 6 patients with defects of varying size and
location, the scrub brush bolster showed a near 100% graft take and no
complications. Conclusions: The dry, sterile surgical scrub brush presents a
readily available and low-cost option for the stenting of small skin grafts and
should be considered a viable method in the armamentarium of available skin graft
bolsters.
PMID- 28702110
TI - Reconstruction of a Nasal Defect With a Radial Forearm Flap Following Trauma of a
Paramedian Forehead Flap.
PMID- 28702111
TI - Innate function of house dust mite allergens: robust enzymatic degradation of
extracellular matrix at elevated pH.
AB - BACKGROUND: Exposure to the house dust mite Dermatophagoides pteronyssinus (D.p.)
increases the risk for developing allergic diseases in humans and their best
friends, the dogs. Here, we explored whether this allergenic mite via its enzymes
may impact the cutaneous extracellular matrix (ECM), which critically determines
epithelial barrier integrity both structurally and functionally. METHODS: Two
extracts obtained from either dust-purified or cultured D.p. bodies were used in
the present study. To assess the potential impact of D.p. on protein components
of the ECM, proteolytic activity of the D.p. extracts were determined by casein
and gelatin gel zymography, and their N-acetyl-beta-hexosaminidase activity
determined colorimetrically. In addition, IgE-dependent and innate degranulation
potential of D.p. was examined in canine MPT-1 mast cells and neurite outgrowth
assay using rat pheochromocytoma PC-12 cells. RESULTS: In gel zymography, both
extracts digested the substrates casein and gelatin in a dose-dependent manner,
especially at alkaline pH, and effective in a wide range of temperatures (30
degrees C-42 degrees C). In particular, a 25-kDa band corresponding to Der p 1,
the major D.p. allergen for humans, was found enzymatically active in both casein
and gelatin gels regardless of the presence of metal ions and of alkaline
conditions. Besides protease activity, N-acetyl-beta-hexosaminidase activity was
detected in both extracts, suggesting that D.p. affects the cutaneous ECM through
deteriorating both proteins and glycosaminoglycans. While both D.p. extracts
induced IgE-dependent mast cell degranulation, much less innate effects on mast-
and neuronal cells were observed. CONCLUSIONS: Our data highlight that D.p. is a
robust source of several distinct enzymes with protease- and N-acetyl-beta
hexosaminidase activities. In alkaline milieu they can degrade components of the
ECM. Therefore, D.p. may contribute to epithelial barrier disruption especially
when the skin surface pH is elevated.
PMID- 28702112
TI - Patient Preference for Transradial Access over Transfemoral Access for
Cerebrovascular Procedures.
AB - PURPOSE: Shared decision-making, when physicians and patients collaborate and
agree on health care decisions, is a key tenant of patient-centered care. Choice
of access site for neurovascular procedures is rarely a shared decision point
between physicians and patients. We present our initial evaluation of patient
preference for radial over femoral access for cerebrovascular procedures.
MATERIALS AND METHODS: IRB approved single-center, prospective, and consecutive
survey of all patients undergoing transradial access for cerebrovascular imaging
and intervention. Primary inclusion criteria were patients who had previously
undergone a transfemoral access procedure and chose to have their second
procedure via a transradial approach. All patients underwent pre-procedural
neurologic and extremity exams (including Barbeau tests for radial access
suitability prior to radial access), post-procedural neurological evaluation and
radial access assessment post-procedure, and complete neurological and radial
access-site evaluation in the neurointerventional outpatient clinic 1-2 week post
procedure. RESULTS: Twenty five consecutive patients who underwent radial access
cerebrovascular procedures after previous femoral access cerebrovascular
procedures (16 diagnostic angiograms and 9 interventional procedures) were
included. No major complications (including hematomas, infection, or delayed
radial artery occlusion) were encountered during the immediate post-procedurral
period or on outpatient follow-up (average 8 days). On immediate post-procedural
examination, 16% had mild bruising and 24% had mild pain at the radial access
site. Of the 25 patients included in this study, 24 strongly preferred radial
access over femoral access and reported that, if they needed another procedure,
they would prefer radial access. CONCLUSION: There was nearly unanimous patient
preference for radial over femoral access for cerebrovascular procedures in this
single-center prospective analysis. There were no major complications and no
incidences of delayed radial occlusion. In the current age of value-based and
patient-centered medicine, the radial approach should be considered for nearly
all neurovascular procedures.
PMID- 28702113
TI - Cost-Effectiveness Analysis of the Unfractionated Heparin versus Low-Molecular
Weight Heparin in Hospitalized Patients with Stroke Due to Atrial Fibrillation in
Shiraz, South of Iran.
AB - BACKGROUND: Patients with atrial fibrillation (AF) make a unique group of
strokes. Unfractionated heparin (UFH) and low-molecular-weight heparin (LMWH) are
among the medications used for preventing blood coagulation. This study was
carried out aiming at analyzing the cost effectiveness of LMWH versus UFH in
hospitalized patients with stroke due to AF with respect to the Iranian
population. METHODS: This randomized study was an economic evaluation of cost
effectiveness with the help of the cross-sectional data of 2013-2015. In this
study, 74 patients had undergone treatment in two groups, before being evaluated.
Half of the patients were treated by LMWH, while the other half was treated by
UFH. Effectiveness criterion was prevention of new stroke recurrence. RESULTS:
Average medical direct costs, non-medical direct costs, and indirect costs of UFH
were 110375 +/- 40411$, 15594 +/- 11511$, and 21723 +/- 19933$, respectively.
Same average medical direct costs, non-medical direct costs, and indirect costs
of LMWH were 99573 +/- 59143$, 9016 +/- 17156$, and 10385 +/- 10598$,
respectively. The number of prevention of new strokes due to AF in LMWH and UFH
was 2 and 0, respectively. Expected effectiveness in LMWH and UFH groups was 0.56
and 0.51, respectively. Moreover, the expected costs were 26737.61$ and
30776.18$, respectively. The incremental cost-effectiveness ratio for stroke due
to AF was -150, 201, 26$ per prevention of stroke recurrence (p-values <= 0/05).
CONCLUSION: The results of the cost-effectiveness analysis of LMWH versus UFH
showed that LMWH is a dominant strategy for patients with stroke due to AF in
Iranian population.
PMID- 28702114
TI - Cerebral Infarction as a Rare Complication of Wasp Sting.
PMID- 28702115
TI - Staged Arterial and Venous Embolizations in Treatment of Type IV Intraosseous
Dural Arteriovenous Fistula.
AB - OBJECTIVE: This is a case report of an adult male with complex type IV
intraosseous DAVF causing severe venous hypertension and bony destruction,
presenting with severe hemotympanum, and a novel way of staged arterial and
venous embolizations to treat the emergent symptoms. METHODS: First and second
stages were direct selective arterial embolizations using Onyx liquid agent. Goal
was to reduce flow into the fistula by embolizing the feeder branch and distal
penetration of the nidus with Onyx. The third stage was performed through the
venous route: the transverse sinus and the sigmoid sinus were embolized using
Penumbra Ruby coils and Onyx, two microcatheters were used and two large coils
were placed simultaneously to form a stable coil mass, and the entire sinus was
embolized using Coils and Onyx. RESULTS: Patient's venous hypertension and degree
of hydrocephalus had significantly decreased after the procedure. He was able to
return to work, but was instructed to avoid heavy lifting and placing anything in
and around his right ear. CONCLUSIONS: Multiple step arterial and venous
embolization procedures were successful in decreasing the frequency of
hemotympanum, degree of hydrocephalus, and improving quality of life of this
patient.
PMID- 28702116
TI - Management of Aggressive Cerebral Dural Arteriovenous Fistulae: Experience Using
Endovascular Embolization.
PMID- 28702117
TI - Balloon Angioplasty for Intracranial Atherosclerotic Disease: A Multicenter
Study.
AB - AIM: To evaluate the role and efficacy of the balloon angioplasty in intracranial
atherosclerotic disease (ICAD) in patients who presented with acute stroke due to
vessel occlusion and in patients with symptomatic disease despite optimum medical
management. METHODS: From 2013 to 2016, a total of 39 patients (24 males and 15
females with a mean age of 64.5 years) underwent balloon angioplasty over a
period of 2 years and 8 months in three different institutions in India. Maverick
balloon catheter (Boston scientific) is used in all the patients. MRI brain with
MR angiogram was done in all the patients prior to intervention. Twenty-three
patients who had underlying severe ICAD presented with acute stroke due to vessel
occlusion. Sixteen patients presented with symptomatic ICAD with recurrent
ischemic attack due to the progressing underlying disease despite optimum medical
management. Technical success, peri-procedural events, and clinical outcomes were
documented for all the patients. RESULTS: Technical success (residual stenosis <
50%) was achieved in 37 cases. Extra cranial carotid stenting was required in 2
patients. In patients with acute stroke presentation (NIHSS score median of
16.5), adjuvant intravenous and intra-arterial tissue plasminogen activator were
given in 8 and 3 patients, respectively, and mechanical thrombectomy (MT) with
solitaire was used in 15 patients. Patients who underwent MT in acute stroke
without ICAD were not included in the study. Reocclusion occurred in one patient
who developed disabling stroke and one patient died of intra-cerebral hemorrhage.
Thus, the mortality of this study is 2%. Clinical outcome was assessed based on
mRS. One-month, three-month, and six-month follow-up was available in >90% of the
patients. MR angiogram on follow-up of nine months was done in 26 patients, and
none of them had restenosis. CONCLUSION: Balloon angioplasty is a safe option and
can be effectively used in patients of ICAD with acceptable risks and promising
outcomes.
PMID- 28702118
TI - Comparison of Nutech Functional Score with European Stroke Scale for Patients
with Cerebrovascular Accident Treated with Human Embryonic Stem Cells: NFS for
CVA Patients Treated with hESCs.
AB - PURPOSE: Stem cell therapy is a promising modality for treatment of patients with
chronic cerebrovascular accident (CVA) in whom treatment other than physiotherapy
or occupational therapy does not address the repair or recovery of the lost
function. In this study, the author aimed at evaluating CVA patients treated with
human embryonic stem cell (hESC) therapy and comparing their study outcomes with
globally accepted European Stroke Scale (ESS) to that with novel scoring system,
Nutech functional score (NFS), a 21-point positional and directional scoring
system for assessing patients with CVA. MATERIALS AND METHODS: Patients diagnosed
with CVA were assessed with NFS and ESS before and after hESC therapy. NFS
assessed the patients in the direction of 1-5 (bad to good), where 5 was
considered as the highest possible grade (HPG). The findings were obtained for
the patients who scored HPG, and had shown improvement by at least one grade.
RESULTS: Overall, 66.7% of patients scored HPG level on the NFS scale and about
62.5% of the patients scored HPG according to the ESS scale. Approximately, 52.2%
patients showed an improvement of 100% (by at least one grade) on NFS scale. None
of the patients showed 100% improvement in the alteration of the score by at
least one grade when scored with ESS. CONCLUSION: NFS and ESS scores show that a
large population of CVA patients was benefitted with hESC therapy. NFS was found
to give more convincing results than ESS, and overcomes the shortcomings of ESS.
PMID- 28702119
TI - A Population-Based Study of the Incidence of Acute Spinal Cord Infarction.
AB - BACKGROUND: There is a paucity of reliable data regarding incidence of acute
spinal cord infarction in population-based studies. OBJECTIVES: To determine the
incidence of acute spinal cord infarction using a population-based design.
METHODS: Medical records and neuroimaging data of all patients with acute spinal
cord infarction from Stearns and Benton Counties, Minnesota, between January 1,
2010 and May 31, 2014 were reviewed. Patients with a first-time diagnosis of
spinal cord infarction were categorized as primary or secondary depending upon
underlying etiology identified. We calculated the incidences of primary and
secondary spinal cord infarction adjusted for age and sex based on the 2010 US
census (189,093 resident populations). RESULTS: The age- and sex-adjusted
incidence of spinal cord infarction was 3.1 [95% confidence interval (CI) 1.6
7.2] per100,000 person-years. The age- and sex-adjusted incidence of primary and
secondary spinal cord infarction was 1.5 [95% CI 0.6-3.6] and 1.6 [95% CI 0.6
3.6] per 100,000 person-years, respectively. The age-adjusted incidences among
men and women were 1.5 [95%CI 0.6-3.7] and 4.6 [95% CI 2.2-8.7] per 100,000
person-years, respectively. No case fatality was observed at one month.
CONCLUSION: We provide incidence rates for acute spinal cord infarction to assist
in future studies and resource allocation.
PMID- 28702120
TI - Inpatient versus Outpatient Management of TIA or Minor Stroke: Clinical Outcome.
AB - BACKGROUND: The management of patients with acute transient ischemic attack (TIA)
or minor stroke is highly variable. Whether hospitalization of such patients
significantly improves short-term clinical outcome is unknown. We assessed the
short-term clinical outcome associated with inpatient versus outpatient
management of patients with TIA or minor stroke. METHODS: We evaluated a
consecutive series of patients with acute TIA or minor ischemic stroke (NIH
Stroke Scale score <= 3) presenting to a single emergency department (ED). We
randomized patients to either hospital-based or outpatient-based management. All
patients underwent interview and examination 7-10 days following the index event.
RESULTS: This study included 100 patients, 41 with TIA and 59 with minor stroke.
Nineteen (46%) of the TIA patients and 29 (49%) of the minor stroke patients
randomized to hospital management, and the remaining 22 TIA patients and 30 minor
stroke patients randomized to outpatient-based management. In the patients with a
minor stroke, neurologic worsening occurred in 6 out of 29 (21%) in the inpatient
arm compared with 3 out of 30 (10%) in the outpatient arm (p = 0.3). In none of
these cases was acute interventional therapy or need for urgent admission
considered medically appropriate. In the patients with a TIA, recurrence of a TIA
occurred in 2 out of 19 (11%) in the inpatient arm compared with 2 out of 22 (9%)
in the outpatient arm (p = 1). None of the patients with a TIA randomized to the
inpatient arm experienced a stroke compared with 1 out of 22 in the outpatient
arm (p = 1). There were no deaths in either group. CONCLUSION: Routine
hospitalization of all patients with TIA or minor ischemic stroke may not
positively affect short-term clinical outcome.
PMID- 28702121
TI - Occurrence of Femoral Nerve Injury among Patients Undergoing Transfemoral
Percutaneous Catheterization Procedures in the United States.
AB - BACKGROUND: The proximity of the femoral nerve to the femoral artery renders it
vulnerable to injury during transfemoral percutaneous catheterization (TPC)
procedures. OBJECTIVE: To determine the incidence of femoral nerve injury in
patients undergoing cardiac catheterization in a nationally representative
inpatient database. METHODS: We analyzed data released annually from the
Nationwide Inpatient Sample. We pooled data from 2002 to 2010 and, using the ICD
9-CM procedure codes, identified patients who underwent TPC. We subsequently
identified occurrences of femoral nerve injury in this cohort. Baseline
characteristics, comorbid conditions, in-hospital complications, and discharge
outcomes-including mortality, mild disability, and moderate-to-severe disability
were compared between patients with femoral neuralgia and those without. RESULTS:
Of the 15,894,201 patients who underwent percutaneous catheterization procedures,
597 (3.8 per 100,000 procedures) developed femoral nerve injury. The incidence of
femoral nerve injury was higher in women: 57% versus 39%, p < 0.004. Patients
with coexisting congestive heart failure or coagulopathy had a non-significant
increase in the incidence of femoral nerve injury. There was no in-hospital
mortality among patients who developed femoral nerve injury, but the rate of
discharge to nursing facilities was higher in this cohort: 17% versus 6%, p <
0.001. After adjusting for age, gender, presence of congestive heart failure, and
coagulopathy, femoral nerve injury during percutaneous catheterization procedures
was independently associated with moderate-to-severe disability at discharge
(odds ratio 2.3; 95% confidence interval 1.4-3.8; p < 0.001). CONCLUSION: Femoral
nerve injury is a rare complication of percutaneous catheterization procedures
that may increase the likelihood of moderate-to-severe disability at patient's
discharge.
PMID- 28702122
TI - GABA signaling stimulates alpha-cell-mediated beta-like cell neogenesis.
AB - Diabetes is a chronic and progressing disease, the number of patients increasing
exponentially, especially in industrialized countries. Regenerating lost insulin
producing cells would represent a promising therapeutic alternative for most
diabetic patients. To this end, using the mouse as a model, we reported that
GABA, a food supplement, could induce insulin-producing beta-like cell neogenesis
offering an attractive and innovative approach for diabetes therapeutics.
PMID- 28702123
TI - The evolution of "Life": A Metadarwinian integrative approach.
AB - It is undeniably very logical to first formulate an unambiguous definition of
"Life" before engaging in defining the parameters instrumental to Life's
evolution. Because nearly everybody assumes, erroneously in my opinion, that
catching Life's essence in a single sentence is impossible, this way of thinking
remained largely unexplored in evolutionary theory. Upon analyzing what exactly
happens at the transition from "still alive" to "just dead," the following
definition emerged. What we call "Life" (L) is an activity. It is nothing other
than the total sum (?) of all communication acts (C) executed, at moment t, by
entities organized as sender-receiver compartments: L = ?C Such "living" entities
are self-electrifying and talking ( = communicating) aggregates of fossil
stardust operating in an environment heavily polluted by toxic calcium.
Communication is a multifaceted, complex process that is seldom well explained in
introductory textbooks of biology. Communication is instrumental to adaptation
because, at the cellular level, any act of communication is in fact a problem
solving act. It can be logically deduced that not Natural Selection itself but
communication/problem-solving activity preceding selection is the universal
driving force of evolution. This is against what textbooks usually claim,
although doubt on the status of Natural Selection as driving force has been
around for long. Finally, adopting the sender-receiver with its 2 memory systems
(genetic and cognitive, both with their own rules) and 2 types of progeny
("physical children" and "pupils") as the universal unit of architecture and
function of all living entities, also enables the seamless integration of
cultural and organic evolution, another long-standing tough problem in
evolutionary theory. Paraphrasing Theodosius Dobzhansky, the very essence of
biology is: "Nothing in biology and evolutionary theory makes sense except in the
light of the ability of living matter to communicate, and by doing so, to solve
problems."
PMID- 28702124
TI - 6-Hydroxy-5-nitrobenzo[d]oxazol-2(3H)-one-A degradable derivative of natural 6
Hydroxybenzoxazolin-2(3H)-one produced by Pantoea ananatis.
AB - Pantoea ananatis is a bacterium associated with other microorganisms on Abutilon
theophrasti Medik. roots. It converts 6-hydroxybenzoxazolin-2(3H)-one (BOA-6-OH),
a hydroxylated derivative of the allelochemical benzoxazolin-2(3H)-one, into 6
hydroxy-5-nitrobenzo[d]oxazol-2(3H)-one. The compound was identified by NMR and
mass spectrometric methods. In vitro synthesis succeeded with Pantoea protein,
with isolated proteins from the Abutilon root surface or with horseradish
peroxidase in the presence of nitrite and H2O2. Nitro-BOA-6-OH is completely
degraded further by Pantoea ananatis and Abutilon root surface proteins. Under
laboratory conditions, 6-hydroxy-5-nitrobenzo[d]oxazol-2(3H)-one inhibits
Lepidium sativum seedling growth whereas Abutilon theophrasti is much less
affected. Although biodegradable, an agricultural use of 6-hydroxy-5
nitrobenzo[d]oxazol-2(3H)-one is undesirable because of the high toxicity of
nitro aromatic compounds to mammals.
PMID- 28702125
TI - Self-organizing actin patterns shape cytoskeletal cortex organization.
AB - Living systems rely, for biological function, on the spatiotemporal organization
of their structures. Cellular order naturally emerges by dissipation of energy.
Consequently, energy-consuming processes operating far from thermodynamic
equilibrium are a necessary condition to enable biological systems to respond to
environmental cues that allow their transitions between different steady-states.
Such self-organization was predicted for the actin cytoskeleton in theoretical
considerations and has repeatedly been observed in cell-free systems. We now
demonstrate in our recent work how self-organizing actin patterns such as
vortices, stars, and asters may allow cells to adjust their membrane architecture
without affecting their cell mechanical properties.
PMID- 28702126
TI - Impairing DNA methylation obstructs memory enhancement for at least 24 hours in
Lymnaea.
AB - Stressor-induced memory enhancement has previously been shown to involve DNA
methylation in the mollusc Lymnaea stagnalis. Specifically, injection of the DNA
methylation inhibitor 5-AZA one hour before exposure to a memory-enhancing
stressor obstructs memory augmentation. However, the duration of the influence of
5-AZA on this memory enhancement has not yet been examined. In this study, 2
memory-enhancing stressors (a thermal stress and exposure to the scent of a
predator) were used to examine whether injection of the DNA methylation inhibitor
5-AZA 24 hours before stress exposure would still impair memory enhancement.
Indeed, it was observed that memory is still obstructed when 5-AZA is injected 24
hours before exposure to either of these stressors in Lymnaea. Understanding that
5-AZA still effectively impairs memory enhancement after a period of 24 hours is
valuable because it indicates that experimental manipulations do not need to be
made within one hour after the injection of this DNA methylation inhibitor and
can instead be made within one day (i.e. 24 hours). These results will allow for
a future examination of the possible involvement of DNA methylation in memory
enhancement related to longer-term stressors or environmental changes. This study
further elucidates the involvement of epigenetic changes in memory enhancement in
Lymnaea, providing insight into the process of memory formation in this mollusc.
PMID- 28702127
TI - Coordinating heart morphogenesis: A novel role for hyperpolarization-activated
cyclic nucleotide-gated (HCN) channels during cardiogenesis in Xenopus laevis.
AB - Hyperpolarization-activated cyclic-nucleotide gated channel (HCN) proteins are
important regulators of both neuronal and cardiac excitability. Among the 4 HCN
isoforms, HCN4 is known as a pacemaker channel, because it helps control the
periodicity of contractions in vertebrate hearts. Although the physiological role
of HCN4 channel has been studied in adult mammalian hearts, an earlier role
during embryogenesis has not been clearly established. Here, we probe the
embryonic roles of HCN4 channels, providing the first characterization of the
expression profile of any of the HCN isoforms during Xenopus laevis development
and investigate the consequences of altering HCN4 function on embryonic pattern
formation. We demonstrate that both overexpression of HCN4 and injection of
dominant-negative HCN4 mRNA during early embryogenesis results in improper
expression of key patterning genes and severely malformed hearts. Our results
suggest that HCN4 serves to coordinate morphogenetic control factors that provide
positional information during heart morphogenesis in Xenopus.
PMID- 28702128
TI - A novel host factor for human respiratory syncytial virus.
AB - Human respiratory syncytial virus (RSV) is the leading viral cause of severe
lower respiratory disease in young children worldwide. As part of a genome-wide
siRNA screen, we recently discovered that actin-related protein 2 (ARP2) is a
host factor in the RSV replication cycle. ARP2 is a major constituent of the
ARP2/3 complex, which catalyzes actin polymerization involved in cell morphology
and motility. In the course of investigating this finding, we also found that RSV
infection of human lung epithelial A459 cells induced filopodia formation and
stimulated cell motility. The increase in filopodia formation was due, at least
in part, to the expression of the RSV fusion F protein. Filopodia formation and
increased cell motility appeared to shuttle RSV particles to nearby uninfected
cells, facilitating virus cell-to-cell spread. ARP2 depletion did not reduce RSV
entry or gene expression early in infection, but reduced subsequent virus
production, filopodia formation, cell motility, and viral spread. Thus, the RSV F
protein, ARP2-mediated actin nucleation, filopodia formation, and cell mobility
all contribute to previously unrecognized mechanisms for RSV cell-to-cell spread
that may promote RSV pathogenesis.
PMID- 28702129
TI - Immunogold-EM analysis reveal brefeldin a-sensitive clusters of auxin in
Arabidopsis root apex cells.
AB - Immunogold electron microscopy (EM) study of Arabidopsis root apices analyzed
using specific IAA antibody and high-pressure freeze fixation technique allowed,
for the first time, vizualization of subcellular localization of IAA in cells
assembled intactly within plant tissues. Our quantitative analysis reveals that
there is considerable portion of IAA gold particles that clusters within vesicles
and membraneous compartments in all root apex cells. There are clear tissue
specific and developmental differences of clustered IAA in root apices. These
findings have significant consequences for our understanding of this small
molecule which is controlling plant growth, development and behavior.
PMID- 28702130
TI - New insights in IBS-like disorders: Pandora's box has been opened; a review.
AB - The most complained gastrointestinal symptoms are chronic diarrhea, bloating and
abdominal pain. Once malignancies and inflammatory bowel diseases are excluded,
irritable bowel syndrome (IBS) and the so called "IBS-like disorders" should be
taken into account. The relationship between IBS as defined by Rome IV criteria
and these clinical conditions is sometimes obscure, since many IBS patients
identify food as a possible trigger for their symptoms. Here, we discuss IBS and
the most common IBS-like disorders (celiac disease, non-celiac gluten
sensitivity, fermentable oligosaccharides, disaccharides, monosaccharides and
polyols (FODMAPs), lactose intolerance, small intestinal bacterial overgrowth
(SIBO), alpha-amylase/trypsin inhibitor (ATIs), nickel allergic contact
mucositis), focusing on epidemiologic, clinical, diagnostic and therapeutic
aspects. Given the lack of specificity of symptoms, clinical investigation will
be facilitated by awareness of these disorders as well as new specific diagnostic
tools.
PMID- 28702131
TI - Distribution pattern of colorectal diseases based on 2300 total colonoscopies.
AB - AIM: We conducted a cross-sectional study to estimate the prevalence of CRD in
our area in East Azerbaijan, Iran. BACKGROUND: Colorectal diseases (CRD) include
a broad spectrum that varies from benign lesions to malignant and cancerous
masses. CRD can be investigated by colonoscopy. Some of these diseases are highly
preventable with timely screening and appropriate planning by the healthcare
system. METHODS: This is a hospital-based, cross-sectional study by the
Gastroenterology Department on patients who underwent colonoscopy between June
2013 and March 2015 in outpatient clinics at private Shahriyar medical center and
Imam Reza University Hospital in Tabriz, East Azerbaijan province, Iran. Chi
square analysis and bivariate Pearson correlation coefficient were applied in
this study using SPSS 20. RESULTS: During the study period, we recruited 2300
patients (1230 men, 1070 women) with the mean and median (Standard Deviation=SD)
age at presentation of 47.10 (0.338) and 47 (16.195) years. The duration of
patients' symptoms ranged from 1 to 480 months, with mean and median (SD) values
of 26.99 (0.902) and 12 (40.76) months, respectively. Despite at least 20 types
of pathologies seen on colonoscopy, normal cases constituted the majority
(32.7%).The most serious diseases in the study were IBD (10.9%), polyps (14.4%)
and cancers (4.9%). Colonoscopic findings had a significant correlation with
patients' age and gender; also, we detected a significant correlation between
patients' chief complaint and colonoscopic findings as well as colonoscopic
pathology samples. CONCLUSION: Despite the ongoing westernization of lifestyle in
our country, the distribution of colorectal diseases in Iran is different from
Western population. It is important to recognize the prevalence of these diseases
in our area to determine exposure factors for management and planning correctly
in health system policies.
PMID- 28702132
TI - Measuring levels of osteopontin as potential biomarker for hepatocellular
carcinoma in Syrian patients.
AB - AIM: This study aims to evaluate plasma osteopontin (OPN) levels as a potential
biomarker for hepatocellular carcinoma (HCC). BACKGROUND: Osteopontin (OPN) is a
secreted glycoprotein that is associated with tumorigenesis and metastasis.
METHODS: We measured plasma levels of OPN in 26 HCC patients, 27 patients with
chronic liver diseases (CLD), and 15 healthy control individuals using a
standardized ELISA kit. RESULTS: The mean plasma OPN level was significantly
higher in the HCC group than the CLD group or the normal control group (p-value
=0.001/<0.0001). Plasma OPN levels were significantly higher in patients with a
tumor size >5 cm in diameter than those with tumors <=5 cm (p=0.02). OPN levels
in the HCC group were not significantly affected by advancing degree of Child
Pugh class. Diagnostic sensitivity and specificity of OPN for HCC were 61% and
82%, respectively (cut-off value: 118.69ng/mL). The area under the ROC curve
(AUC) value for OPN was 0.784. However, the AUC value was 0.844 for AFP.
CONCLUSION: The plasma levels of OPN show low diagnostic accuracy for HCC
compared to AFP. However, OPN may have a complementary role in diagnosing HCC in
patients with non-diagnostic levels of AFP.
PMID- 28702133
TI - Cytotoxic effect of rosemary extract on gastric adenocarcinoma (AGS) and
esophageal squamous cell carcinoma (KYSE30) cell lines.
AB - AIM: The present study was conducted to survey the potential cytotoxic influence
of freeze-dried aqueous extract of its fruits on gastrointestinal cell lines,
namely AGS (human gastric carcinoma) and KYSE30 (human esophageal squamous cell
carcinoma. BACKGROUND: Rosemary (Rosmarinus officinalis) is a wild medicinal
plant shown to have anticancer activity. Carnosic and rosmarinic acids are
compounds, obtained from it through several extraction methods. METHODS: The
aqueous extract of the fruits of R.officinalis was freeze-dried, and KYSE30 and
AGS cancer cell lines were treated with crude extract. Cytotoxic effect of the
extracts on the cell lines was examined using 3-(4, 5-Dimethylthiazol-2-yl)-2,5
diphenyltetrazolium bromide (MTT) and neutral red assay. Apoptotic cells were
detected with ethidium bromide/acridine orange (EB/AO). Cell-cycle distributions
were evaluated by flow cytometry. RESULTS: IC50 values were 4.1, 1.8 and 1.3
mg/mL for AGS cell lines after 24, 48 and 72 hours by MTT assay, respectively,
and 4.4, 2.1 and 1.1 mg/mL by neutral red assay, respectively. IC50 values for
KYSE30 cell lines were 600, 180 and 150 mg/mL after 24, 48 and 72 hours by MTT
assay, and 860, 270 and 230 mg/mL by neutral red. EB/AO staining increased in
apoptotic cells. After 24 h of treatment at different concentrations, significant
increases and decreases in population were shown at G2/M and G1 phases,
respectively. CONCLUSION: The aqueous extract of the fruits of R.officinalis was
freeze-dried, and KYSE30 and AGS cancer cell lines were treated with crude
extract. Cytotoxic effect of the extracts on the cell lines was examined using 3
(4, 5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and neutral red
assay. Apoptotic cells were detected with ethidium bromide/acridine orange
(EB/AO). Cell-cycle distributions were evaluated by flow cytometry.
PMID- 28702134
TI - Evaluating the frequency of MLH-1 Loss in serrated polyps of colon: a single
center study from Southern Iran.
AB - AIM: Evaluation of the role of MLH-1 loss in serrated polyps of colon in a
population of South of Iran. BACKGROUND: There has been extensive change in
classification and pathogenesis of serrated polyps of the colon during the last
10 years. The new classification is mostly based on the knowledge of the
molecular pathogenesis and the rate of progression to colorectal cancer in these
types of polyps. One of the most common and early lesions in molecular
pathogenesis of serrated colorectal cancer is loss of MLH-1. PATIENTS AND
METHODS: In this study over 2 years (2012-13), 78 cases of colorectal polyps with
serrated morphology resected in hospitals affiliated with Shiraz University of
Medical Sciences were reclassified and investigated for MLH-1 loss by
immunohistochemical method. RESULTS: Out of the 78 colorectal polyps, 64 were
classified as hyperplastic polyp (HP) and 14 as sessile serrated adenoma/polyp
(SSA/P). There was no case of traditional serrated adenoma. Three cases of SSA/P
located in right colon showed dysplasia. MLH-1 loss was detected only in these 3
cases. No case of HP or SSA/P without dysplasia showed MLH-1 loss. CONCLUSION:
SSA/P is not a common serrated polyp in our population, i.e. it is much less
common than HP. Although MLH-1 loss in serrated polyps of colon is overall rare,
it is fairly common in dysplastic right sided SSA/P, which confirms this
molecular change as an early event in serrated carcinogenesis.
PMID- 28702135
TI - Effect of TGF-beta/smad signaling pathway blocking on expression profiles of miR
335, miR-150, miR-194, miR-27a, and miR-199a of hepatic stellate cells (HSCs).
AB - AIM: The aim of this study was to determine the effect of inhibition of TGF
beta/smad signaling on the expression profiles of miR-335, miR-150, miR-194, miR
27a, miR-199a of hepatic stellate cells (HSCs). BACKGROUND: Liver fibrosis is
excessive deposition of extracellular matrix proteins due to ongoing inflammation
and HSC activation that occurs in most types of chronic liver diseases. Recent
studies have shown the importance of microRNAs in the pathogenesis of chronic
liver diseases. METHODS: In this study, for inhibition of TGF-beta smad-signaling
pathway, expressing Smad4 shRNA plasmids were transfected into HSCs.
Subsequently, using Real Time-PCR, we measured the expression levels of miR-335,
miR-150, miR-194, miR-27a and miR-199a. RESULTS: Gene expression analysis showed
that downregulation of Smad4 by vector Smad4shRNA significantly increased the
expression levels of miR-335 (P<0.01) and miR-150 (P<0.001) and decreased the
expression level of miR-27a (P<0.05). CONCLUSION: The results of this study
suggest that blocking TGF-beta smad-signaling can also differentially modulate
microRNA expression in support of activation and fibrogenesis of HSCs.
PMID- 28702136
TI - Chronic cholecystitis in the pediatric population: an underappreciated disease
process.
AB - AIM: We hypothesize that chronic cholecystitis accounts for the majority of
inflammatory diseases in the pediatric population and it is difficult to predict
with preoperative ultrasound. BACKGROUND: Despite the increase in gallbladder
disease, there is a paucity of data on pediatric cholecystitis. Most pediatric
studies focus on cholelithiasis and biliary dyskinesia rather than inflammatory
gallbladder disease. METHODS: We performed a single center retrospective review
of all patients who underwent cholecystectomy from 1/1/10 - 1/1/15. Relevant data
was extracted, including age, sex, acute vs. chronic presentation, duration of
symptoms, preoperative imaging findings, and surgical pathology results. RESULTS:
Out of the 170 patients identified, there were 129 (75.9%) females and 41 (24.1%)
males. The average age was 14 years (range 4-23 years). Seventy-six patients
presented with acute symptoms with an average duration of pain of 2 days. Ninety
four patients presented with chronic symptoms and had an average duration of pain
of 7.4 months. Eight patients (4.7%) had preoperative ultrasound that suggested
inflammation, while the remaining showed only cholelithiasis. Pathology revealed
chronic cholecystitis in 148 (87.1%). Among those who had pathologic evidence of
chronic cholecystitis, preoperative inflammation was seen in only 5 patients
(3.3%). CONCLUSION: Chronic cholecystitis accounts for the majority of pediatric
inflammatory diseases. These data suggest that most pediatric patients experience
episodes of inflammation prior to cholecystectomy. Underappreciated gallbladder
inflammation may delay surgical referral, increase emergency department and
primary doctor visits, and lead to more difficult operations. Surgeons should
consider early cholecystectomy when cholelithiasis and symptoms are present.
PMID- 28702137
TI - Phage therapy: assessment of the efficacy of a bacteriophage isolated in the
treatment of salmonellosis induced by Salmonella enteritidis in mice.
AB - AIM: This work aims to isolate and perform comparative studies of a phages active
against a Salmonella enteritidis strain from Iran. Also, suitable phage
candidates for therapy of mice will be selected. BACKGROUND: Bacteriophage is of
particular interest as a biocontrol agent in the prevention of food-borne
illnesses. In recent years tend to use bacteriophages to control pathogenic
bacteria has increased. A bacteriophage is considered to be a potent antibiotic
alternative for treating bacterial infections. METHODS: the specific phages
against Salmonella Enteritidis was isolated and candidates for therapy of mice
will be selected. Mouses divided into the six specific groups. Groups of mice
were as follows: A: Bacteri (control) B: Bacteri+ bacteriophage (Simultaneous),
C: Bacteri + bacteriophage Four days later, D: Bacteriophage + bacteri four days
later E: Bacteri+ Ciprofloxacin (Simultaneous) F: Bacteri+ ciprofloxacin+
bacteriophage (Simultaneous). RESULTS: In this study, a lytic bacteriophage is
isolated and it shows that phage has a head size of 46 nm and without a tail, by
using an electron microscope. Oral administration of a single dose of 2 * 109
PFU/mouse bacteriophage enable to protect mouse against salmonellosis and it
causes treatment of salmonellosis in mice. CONCLUSION: The use of this phage
compared to ciprofloxacin shows that in addition of the treatment of mouse, it
also prevents weight loss.
PMID- 28702138
TI - Prevalence and clinical features of Cryptosporidium infection in hemodialysis
patients.
AB - AIM: This cross-sectional study aims to assess the prevalence of Cryptosporidium
in hemodialysis patients compared with healthy individuals in central Iran from
August 2014 to January 2015. BACKGROUND: Cryptosporidiosis is a major cause of
acute and persistent diarrhea with significant morbidity and mortality in
immunocompromised patients such as those undergoing renal dialysis. METHODS:
Three stool samples were collected from 330 hemodialysis patients and 150 healthy
individuals on 3 consecutive days. The samples were screened for Cryptosporidium
infection using formalin-ether sedimentation and modified Ziehl-Neelsen staining.
Demographic variables as well as risk factors were recorded. RESULTS: Out of 330
dialysis patients and 150 healthy individuals, 10 (3%) and 1 (0.7%) were infected
with Cryptosporidium, respectively. We found statistically significant
differences between infection and place of residency, hygiene status, education
level, diarrhea, and abdominal pain in the two groups (p<0.05). On the other
hand, there was no relationship between infection and sex, contact with domestic
animals, fever, vomiting, nausea, flatulence, anorexia, duration of dialysis and
underlying disorders in the two groups. Also, there was a statistically
significant difference between age and infection in hemodialysis patients
(p=0.003). A higher infection rate was observed in patients under 20 years of
age. CONCLUSION: Risk factors for Cryptosporidium infection must be controlled.
We strongly recommended that stool samples from such patients, especially those
with severe or prolonged diarrhea, should be examined with modified Ziehl-Neelsen
staining for appropriate and timely treatment.
PMID- 28702139
TI - Ramipril-associated cholestasis in the setting of recurrent drug-induced liver
injury.
AB - Aim: Angiotensin-converting enzyme inhibitors (ACEIs) are commonly used to treat
hypertension. Although generally well tolerated, the adverse effects of ACEIs
include hypotension, cough, acute kidney injury and hyperkalemia. Rare reports of
ACEI-induced hepatotoxicity have been described, most notably a cholestatic
pattern of injury related to captopril. A 67-year-old male presented to the
emergency department with a three-week history of jaundice, pruritis and
weakness. Eight weeks before, he began taking ramipril and clopidogrel. His past
medical history was significant for previous acute cholestatic liver injury
approximately 20 years earlier, which was attributed to methimazole. Abnormal
blood work demonstrated aspartate aminotransferase (AST) 47 U/L, alanine
aminotransferase (ALT) 46 U/L, total bilirubin 230 umol/L, direct bilirubin 176
umol/L, and alkaline phosphatase (ALP) 470 U/L. Abdominal ultrasound and magnetic
resonance cholangiopancreatography showed no bile duct obstruction. Further work
up was negative for infectious, autoimmune, or other causes. Percutaneous liver
biopsy showed marked cholestasis. With discontinuation of ramipril, the patient
demonstrated prolonged cholestasis with partial biochemical improvement and was
discharged after six weeks in hospital. This case represents the first described
cross reactivity between ramipril and methimazole, illustrating the complex and
poorly understood nature of DILI. Despite the relatively few instances of ACEI
induced liver hepatotoxicity, consideration should be given to discontinuation of
ramipril in situations of unknown liver damage.
PMID- 28702140
TI - Acute Epstein - Barr virus hepatitis without mononucleosis syndrome: a case
report.
AB - Elevated liver enzymes accompanied by Infectious Mononucleosis syndrome are
widely seen in primary Epstein-Barr virus infection while acute symptomatic
hepatitis without typical presentations of EBV is extremely rare. In the
following report, we present a patient with acute isolated hepatitis due to
laboratory confirmed Epstein-Barr virus.
PMID- 28702141
TI - The necessity of gut microbiome characterization in diseases prevention and
therapy.
PMID- 28702142
TI - Recent advances in nutrition.
PMID- 28702143
TI - CXCR4 expression is associated with time-course permanent and temporary
myocardial infarction in rats.
AB - OBJECTIVES: Experimental myocardial infarction triggers secretion of Stromal cell
derived factor1 and lead to increase in the expression of its receptor "CXCR4" on
the surface of various cells. The aim of this study was to evaluate the
expression pattern of CXCR4 in peripheral blood cells following time-course
permanent and temporary ischemia in rats. MATERIALS AND METHODS: Fourteen male
Wistar rats were divided into two groups of seven and were placed under permanent
and transient ischemia. Peripheral blood mononuclear cells were isolated at
different time points, RNAs extracted and applied to qRT-PCR analysis of the
CXCR4 gene. RESULTS: Based on repeated measures analysis of variance, the
differences in the expression levels of the gene in each of the groups were
statistically significant over time (the effect of time) (P<0.001). Additionally,
the difference in gene expression between the two groups was statistically
significant (the effect of group), such that at all times, the expression levels
of the gene were significantly higher in the permanent ischemia than in the
transient ischemia group (P<0.001). Moreover, the interactive effect of time
group on gene expression was statistically significant (P<0.001). CONCLUSION:
CXCR4 is modulated in an induced ischemia context implying a possible association
with myocardial infarction. Checking of CXCR4 expression in the ischemic changes
shows that damage to the heart tissue trigger the secretion of inflammatory
chemokine SDF, Followed by it CXCR4 expression in blood cells. These observations
suggest that changes in the expression of CXCR4 may be considered a valuable
marker for monitoring myocardial infarction.
PMID- 28702144
TI - Establishment of human hair follicle mesenchymal stem cells with overexpressed
human hepatocyte growth factor.
AB - OBJECTIVES: Chronic liver disease has become a major health problem that causes
serious damage to human health. Since the existing treatment effect was not
ideal, we need to seek new treatment methods. MATERIALS AND METHODS: We utilized
the gene recombination technology to obtain the human hair mesenchymal stem cells
which overexpression of human hepatocyte growth factor (hHGF). Furthermore, we
verified the property of transfected cells through detecting surface marker by
flow cytometry. RESULTS: We show here establishment of the hHGF-overexpressing
lentivirus vector, and successfully transfection to human hair follicle
mesenchymal stem cells. The verified experiments could demonstrate the human hair
follicle mesenchymal stem cells which have been transfected still have the
properties of stem cells. CONCLUSION: We successfully constructed human hair
follicle mesenchymal stem cells which overexpression hHGF, and maintain the same
properties compared with pro-transfected cells.
PMID- 28702145
TI - Catheter-related urinary nosocomial infections in intensive care units: An
epidemiologic study in North of Iran.
AB - BACKGROUND: Urinary tract infection (UTI) is one of the most common infections in
developing countries. The aim of this study was to investigate the incidence of
nosocomial catheter- associated UTI and its related factors in hospitalized
patients in intensive care units of hospitals affiliated to Mazandaran University
of Medical Sciences, in 2014. METHODS: This cross-sectional study was conducted
on patients who were admitted in hospitals and urinary catheterization was
performed for them. Beds of intensive care units were followed-up for the
occurrence of catheter-associated UTI for 14 months. Data were analyzed using
SPSS Version 16. RESULTS: Our results showed that of the 1409 patients (11648
catheter - days), the incidence of catheter-related UTI was 18.2% (among 256
individuals) equals to 21.987 per 1,000 catheter - days. E. coli was the most
important cause of UTI. The results show that the history of the underlying
disease, duration of catheterization and perineal washing were significantly
associated with the incidence of UTIs. CONCLUSION: The findings of this study
show a high incidence of UTIs caused by catheters in ICU. The incidence of this
infection increased hospital length of stay and hospital cost. It seems that the
necessary use of urinary catheters and its reduced duration use can be effective
in decreasing this incidence.
PMID- 28702146
TI - Are polymorphisms in MTRR A66G and MTHFR C677T genes associated with congenital
heart diseases in Iranian population?
AB - BACKGROUND: The 5, 10-methyleneterahydrofolate reductase (MTHFR) and methionine
synthase reductase (MTRR) are two essential enzymes involved in folate
metabolism. The relationship between genetic polymorphisms and congenital heart
defects (CHDs) is inconsistent. Our aim was to investigate the association
between two well-known polymorphisms of MTHFR and MTRR genes, C677T and A66G,
respectively, and CHDs in Iranian patients. METHODS: We enrolled 74 patients with
ventricular septal defect (VSD) and 79 with tetralogy of fallot (TOF) along with
147 healthy controls. C677T and A66G polymorphisms were detected using tetra
primer ARMS (amplification refractory mutation system) PCR. RESULTS: Individuals
carrying homozygote mutant (TT) genotype of C677T polymorphism represented the
highest risk for CHDs (OR=7.3, 95% CI: 0.8-61, P=0.06). Also, significantly
increased risk of VSD was observed in individuals with TT genotype (OR=10, 95%
CI: 1-92.2, P=0.04). However, the frequency for variant allele (T) of C677T
polymorphism was not statistically different between cases and controls (16.3%
and 20.9%, respectively). For A66G polymorphism, we found that AG and GG
genotypes had higher frequencies in the patients (48.4% and 21.6% respectively)
than controls (42.9% and 15.6%, respectively). In line with this, combined AG+GG
genotype represented with significantly elevated risk of CHDs (OR=1.6; 95% CI: 1
2.6, P=0.03). AG+GG combination was also identified as a risk factor for TOF
(OR=1.8, 95% CI: 1-3.3, P=0.04). CONCLUSION: We demonstrated that C677T
polymorphism of MTHFR gene was significantly associated with VSD in our patients.
Our study also suggested that A66G polymorphism of MTRR gene may contribute to
the development of TOF in Iranians.
PMID- 28702147
TI - Does adjuvant chemotherapy change bone mineral density and related serum
biomarkers in women with breast cancer?
AB - BACKGROUND: The primary objective of this study was to assess BMD change in
Iranian females with breast cancer. METHODS: A sample of 73 female breast cancer
patients treated with adjuvant chemotherapy either alone or followed by
radiotherapy between March 2013 and February 2016 were considered for this study.
Bone mineral density (BMD) change was evaluated by measuring z-score of lumbar
spine, femoral neck (right and left side) as well as biochemical measurements.
With respect to WHO categorization for the treatment of osteoporosis, patients
were categorized as normal BMD, osteopenic and all analysis was done separately.
RESULTS: In women with normal BMD, lumbar spine and femoral neck (right side) z
score decreased significantly by 15.7 and 39%, respectively (p<0.05). In
osteoporosis group, there was no BMD change in any of the lumbar or femoral neck
z-scores. However, in osteopenic patients, femoral neck BMD decreased
significantly by 40.9% after 8 months (p=0.003). The level of all measured
biomedical markers such as Ca, Alb, P and vitamin OHD decreased significantly in
a follow-up visit in both osteoporosis and normal BMD. CONCLUSION: Our results
revealed that adjuvant chemotherapy led to unfavorable effects on lumbar spine
and femoral neck means z-score during 8 months. Also, unfavorable changes in
biochemical markers appeared in all groups.
PMID- 28702148
TI - Comparative analysis of resected prostate weight in diabetic and non-diabetic
benign prostatic hyperplasia Patients.
AB - BACKGROUND: Benign prostatic hyperplasia (BPH) is the most common benign tumor in
men. The etiology of BPH is still unresolved and multiple systems are likely to
be involved. The effects of diabetes on urinary system are a risk factor for BPH.
We then assessed the effects of diabetes on the parameters related to BPH,
especially weight and volume. METHODS: This study was conducted on patients with
BPH who underwent surgery during 2010-2013. The patients' demographic and
clinical data including age, height, weight, history of diabetes, abdominal
sonography, prostate-specific antigen(PSA), fasting blood sugar (FBS),
triglyceride, and cholesterol, resected sample weight, and pathological diagnosis
were extracted. RESULTS: The mean age of all 225 patients (35 (15.6%) diabetic
patients and 190 (84.4%) non-diabetic patients) who entered the study was 71.5+/
8.7 years. The patients were divided in to 3 body mass index (BMI) groups: 48
(21.3%) were normal, 151 (67.1%) were overweight and 26 (11.6%) were obese. The
mean weight of resected prostate was higher in diabetic patients (22.9+/-6.9 vs
21.7+/-14.3, P=0.02). The resected prostate weight had a significant relationship
with BMI (P=0.001), prostate-specific antigen (PSA) level (P=0.001), and prostate
volume sonography (P=0.001). No significant relationship was detected between
resected prostate weight with age, FBS and triglyceride however, it is
significant with cholesterol. CONCLUSION: We concluded that diabetes has a role
in the development and progression of BPH with effect on prostate weight and
volume. As well, BMI is a risk factor in BPH progression.
PMID- 28702149
TI - Postoperative antibiotic therapy after appendectomy in patients with non
perforated appendicitis.
AB - BACKGROUND: Appendectomy intra-abdominal is the most frequently performed
emergency surgery. This study was conducted to determine the role of
postoperative antibiotics in reducing surgical site infections (SSIs) and abscess
formation after open appendectomy. METHODS: In the Department of Surgery, Shahid
Beheshti Hospital, Babol, Iran, from October 2013 to October 2014 one hundred and
fifty two patients, who underwent appendectomy for nonperforated appendicitis
(NPA) and fulfilled the selection criteria, were randomized into two groups.
Group A patients received a single dose of preoperative antibiotics (ceftriaxone
and metronidazole) and group B patients received the same regimen, in addition,
antibiotics were administered 24 hours postoperatively. Patients of both groups
were followed-up for 30 days to assess the postoperative infectious
complications. RESULTS: Both groups comprised 76 patients, as well both groups
were compared in baseline characteristics. Statistically, there was no
significant difference in rates of SSIs between both groups. None of the patients
developed intra-abdominal collection. CONCLUSION: Single dose of preoperative
antibiotics (ceftriaxone and metronidazole) was sufficient in reducing SSIs after
appendectomy for NPA. Postoperative antibiotics did not add an appreciable
clinical benefit in these patients.
PMID- 28702150
TI - Adding ofloxacin to standard triple-drug regimens increased the Helicobacter
pylori eradication rate: Data from randomized clinical trial.
AB - BACKGROUND: The rate of Helicobacter pylori (H.pylori) eradication in dyspeptic
patients using bismuth- based triple therapy is low due to bacterial that are
resistant to antibiotics. The results of recent studies regarding levofloxacin
have been encouraging, but the high cost of treatment prevents its routine
administration. We, therefore, performed the present double-blind clinical trial
to compare the efficiency of quadruple-drug regimen containing ofloxacin,
clarithromycin, amoxicillin, and omeprazole and the same standard triple-therapy
regimen minus ofloxacin in H. pylori positive dyspepsia. METHODS: The study
patients were recruited among dyspeptic patients requiring gastroscopy. Patients
with the history of H.pylori treatment, renal failure and pregnancy were
excluded. Diagnosis of H.pylori infection was confirmed by rapid urease test and
response to treatment was confirmed via negative urease breath test (UBT) 20 days
after completion of treatment. Patients were allocated intermittently to standard
triple therapy containing amoxicillin, clarithromycin, omeprazole alone or plus
ofloxacin for ten days. Response to treatment was compared between the two
groups. RESULTS: A total of 140 patients entered the study (70 patients in each
group). At endpoint 30 (42.9%) patients of group 1 and 39 (55.7%) patients of
group 2 became asymptomatic. Furthermore, 55 (78.6%) patients of group 1 and 66
(94.3%) patients of group 2 revealed negative urea breath test (P= 0.01).
CONCLUSION: This study indicates adding ofloxacin to standard triple-therapy for
H.pylorri infection significantly increases the rate of eradication. These
findings highlight ofloxacin as empiric treatment of H. pylori infection.
PMID- 28702151
TI - Human enteroviruses in cerebrospinal fluid of children with suspected aseptic
meningitis: A study in northern Iran.
AB - BACKGROUND: Enterovirus (EV) infections are one of the most common causes of
aseptic meningitis in pediatrics. To diagnose EV meningitis, virus isolation in
cell cultures is often time consuming and lacks sensitivity to be of clinical
relevance. This makes the virus culture results difficult to interpret. The rapid
detection of EVs in cerebrospinal fluid (CSF) by molecular diagnostic techniques
may improve the management of patients with aseptic meningitis. The purpose of
the present study was to develop a more convenient and sensitive alternative
technique to viral culture. The current investigation aimed to explore the
prevalence of EVs in CSF of children with suspected aseptic meningitis in
northern Iran, between June 2014 and March 2015 via the one-step real-time RT-PCR
technique. METHODS: A single center cross-sectional study was carried out on 50
children suspected with aseptic meningitis, aged 6 months to 13 years. The
presence of EV RNA in CSF samples was screened by the use of qualitative one-step
real-time RT-PCR. RESULTS: Enteroviral RNA was detected in 9 (18%) subjects using
the one-step real-time RT-PCR assay. There was significant difference between EV
positive and negative subjects regarding mean age (P=0.023), mean lymphocyte
percentage (P=0.001) and mean glucose levels in CSF (P=0.037). The disease onset
data indicate that the majority of EV meningitis occurred in the summer.
CONCLUSION: This study provides the first data on the prevalence and epidemiology
of EV infections in children with suspected aseptic meningitis in northern Iran.
PMID- 28702152
TI - Brucella pericarditis: A forgotten cause of chest pain.
AB - BACKGROUND: Brucellosis pericarditis is an extremely rare involvement of the
cardiovascular system with Brucella species that has worldwide distribution and
is endemic in many provinces of Iran. CASE PRESENTATION: The present report
describes an exceptional case of pericardial involvement by Brucella melitensis
in a 50- year-old woman. The patient presented with night sweats, mild fever,
weight loss, and chest pain. CONCLUSION: Pericarditis occurs during the course of
brucellosis as an isolated cardiac symptom and may be asymptomatic or may be
manifested with chest pain as ischemic heart disease.
PMID- 28702153
TI - Neurobrucellosis in systemic lupus erythematosus.
AB - BACKGROUND: Brucellosis is a zoonotic infection which is endemic in many
countries. It is a multisystem disease which may present with a broad spectrum of
clinical manifestations and complications. Neurobrucellosis is an uncommon
complication of brucellosis. CASE PRESENTATION: A 25-year-old woman with a
history of lupus for 5 months referred to the emergency ward of Shahid Beheshti
Hospital of Qom due to vertigo, drop attack and a convulsion episode from the
previous day. She was unable to move at initial evaluation, and her upper and
lower extremities were spastic. She had blurred vision one day after admission.
Based on her past history and suspecting neurological pulmonary presentations,
treatment with immunosuppressive drugs was started and brain MRI was performed.
According to the MRI mode and endemic area, neurobrucellosis was suspected and
2ME and Wright tests were performed. Wight test was 1.5120 while 2ME test was
1.640 which were strongly positive. So, with neurobrucellosis diagnosis, the
patient was treated but unfortunately 4 days later, after respiratory apnea, she
was pronounced dead. CONCLUSION: In endemic areas for brucellosis,
neurobrucellosis should always be kept in mind in the differential diagnosis of
neurological and psychiatric cases that are encountered.
PMID- 28702154
TI - A case report on late presentation of occult dural lesions.
AB - BACKGROUND: Occult dural injuries are rare and can occur as a result of major or
minor head injury. These injuries usually manifest with cerebrospinal fluid
rhinorrhea alone, or with meningitis and cerebral abscess, sometimes many years
after the original injury. CASE PRESENTATION: We present a case of occult dural
injury with endocranial complications which occurred in a 34 year old man, with a
history of head injury forty-three years ago. The patient presented with a triad
of findings; meningitis, CSF rhinorrhoea and pneumocephalus. He was managed
conservatively with intravenous antibiotics and observation and made a full
recovery. The presence of acute endocranial symptoms and particularly these three
findings in a patient with a previous history of head injury, no matter how long
it had been should raise suspicion of the presence of an occult dural injury.
CONCLUSION: It need to retain a high index of suspicion for occult dural injury
in patients who present with endocranial symptoms of unknown origin, especially
if there is a previous history of head injury.
PMID- 28702155
TI - Unusual presentation of an abdominal foreign body: A case report.
AB - BACKGROUND: Insertion of rectal foreign bodies intentionally or unintentionally
is not unusual. CASE PRESENTATION: A 19-years-old unmarried male was admitted to
our hospital due to a lump of left lower quadrant of abdomen. He denied sexual
assault .The abdomen was soft on physical examination. Abdominal x-ray and CT
scan showed a foreign body in lower abdomen and pelvis. The patient was operated
and a slice of glass was extracted. CONCLUSION: In patients with rectal foreign
body, the history is not always reliable and sexual assault may deny. The foreign
object inserted in the rectum may migrate to peritoneal cavity without
peritonitis.
PMID- 28702156
TI - Clinical presentation of acute appendicitis in Babol; northern of Iran.
PMID- 28702157
TI - Food bioactive componts, a possible adjuvant for H.pylori eradication.
PMID- 28702158
TI - Hematologic disorder: A manifestation of helicobacter pylori infection.
PMID- 28702159
TI - Hodgkin's Lymphoma in a Man with Dilated Cardiomyopathy and Paraneoplastic
Ataxia: A Therapeutical Challenge.
AB - Hodgkin's lymphoma is a cancer of the lymphatic system. We report the case of a
man with Hodgkin's lymphoma and cardiomyopathy, for which the dilemma was whether
to use the standard protocol - putting the patient at risk of worsening of heart
failure, but giving him a good chance of full recovery - or not. The standard
protocol was given and the patient made a full recovery without cardiac
complications.
PMID- 28702160
TI - BK Virus-associated Hemorrhagic Cystitis in Patients with Allogeneic
Hematopoietic Cell Transplantation: Report of Three Cases.
AB - BK viras is a human polyoma viras. It is acquired in early childhood and remains
life-long latent in the genitourinary system. BK virus replication is more common
in receiving immunosuppressive therapy receiving patients and transplant
patients. BK virus could cause hemorrhagic cystitis in patients with allogeneic
stem cell transplantation. Hemorrhagic cystitis is a serious complication of
hematopoietic stem cell transplantation. Hemorrhagic cystitis could cause
morbidity and long stay in the hospital. Diagnosis is more frequently determined
by the presence of BK virus DNA detected with quantitative or real-time PCR
testing in serum or plasma and less often in urine. The reduction of
immunosuppression is effective in the treatment of BK virus infection. There are
also several agents with anti-BK virus activity. Cidofovir is an active agent
against a variety of DNA viruses including poliomyoma viruses and it is a
cytosine nucleotide analogue. Intravenous immunoglobulin IgG (IVIG) also includes
antibodies against BK and JC (John Cunningham) viruses. Hereby, we report three
cases of hemorrhagic cystitis. Hemorrhagic cystitis developed in all these three
cases of allogeneic stem cell transplantation due to acute myeloid leukemia
(AML). BK virus were detected as the cause of hemorrhagic cystitis in these
patients. Irrigation of the bladder was performed. Then levofloxacin 1 x750 mg
intravenous and IVIG 0.5 gr/kg were started. But the hematuria did not decreased.
In the first case, treatment with leflunomide was started, but patient died due
to refractory AML and severe graft-versus-host disease after 4th day of
leflunamide and levofloxacin treatments. Cidofovir treatment and the reduction of
immunosuppressive treatment decreased the BK virus load and resulted symptomatic
improvement in the second case. Initiation of cidofovir was planned in the third
case. Administration of cidofovir together with the reduction of
immunosuppression in the treatment of hemorrhagic cystitis associated with BK
virus in allogeneic stem cell transplant recipients could be a good option.
PMID- 28702162
TI - Plant performance was greater in the soils of more distantly related plants for
an herbaceous understory species.
AB - Growing evidence suggests that plant-soil interactions have important
implications for plant community composition. However, the role of phylogenetic
relatedness in governing interactions between plants and soil biota is unclear,
and more case studies are needed to help build a general picture of whether and
how phylogeny might influence plant-soil interactions. We performed a glasshouse
experiment to test whether degree of phylogenetic relatedness between Aquilegia
canadensis and six co-occurring heterospecifics affects A. canadensis biomass
through soil legacy effects. We also compared performance of A. canadensis in
soils conditioned by invasive Alliaria petiolata versus native heterospecifics,
hypothesizing that conditioning by A. petiolata would suppress the performance of
the focal native plant. A. canadensis performed significantly better in distant
relatives' soils than in close relatives' soils, and this effect disappeared with
soil sterilization, consistent with close relatives sharing similar pathogens.
Contrary to our expectations, soils conditioned by the invasive species A.
petiolata versus by native species had similar effects on A. canadensis. The
greater performance of A. canadensis in soils of more versus less distant
relatives is consistent with a hypothesis of phylogenetically constrained
pathogen escape, a phenomenon expected to promote coexistence of phylogenetically
distant species. However, pairwise plant-soil feedback experiments are needed to
create a stronger coexistence prediction.
PMID- 28702163
TI - Slow stamen movement in a perennial herb decreases male-male and male-female
interference.
AB - Approximately 80 % of angiosperm species produce hermaphroditic flowers, which
face the problem of male-male sexual interference (one or more anthers gets in
the way of disseminating pollen from other anthers) or male-female sexual
interference (the pistil interferes with disseminating pollen from the anthers by
preventing the anther from touching a pollinator, or the anther prevents
pollinator from depositing outcross pollen on the stigma). Slow stamen movement
in hermaphrodite flowers has been interpreted as an adaptation for reducing male
male sexual interference. Using slow stamen movement in Lychnis cognata
(Caryophyllaceae), this study presents new evidence that this phenomenon can
reduce both male-male and male-female sexual interference. Ten stamens in L.
cognata flowers vertically elongated their filaments in two batches and displayed
similar patterns in pollen dispensing. More importantly, 10 stamens bend out of
the floral centre by curving the filament also in 2 batches and pollen grains
located at the flower centre displayed the highest viability. Thus, three stages
of stamen movement can be identified, comprising two male stages (M1 and M2) and
one female stage (F). We found that the main pollinator for L. cognata,
Bhutanitis yulongensis (Papilionodae) generally preferred M1 flowers.
Manipulation experiments show that vertical stamen movement enabled the anthers
to dehisce at different times to prolong the presentation of pollen grains.
Horizontal movement of the stamen decreased both male-male and male-female
interference. However, vertical stamen movement had a minor role in increasing
amount of pollen received by the stigma. This study provides the first direct
experimental evidence of concurrent male-male and male-female interference in a
flower. We suggest that the selection pressure to reduce such interference might
be a strong force in floral evolution. We also propose that other selective
pressure, including pollen dispensing mechanisms, pollen longevity, pollinator
behaviour and weather, might contribute to floral evolution.
PMID- 28702164
TI - A case of an anomalous biliary tract diagnosed preoperatively.
AB - We describe a 48-year-old man with cholecystolithiasis whose preoperative
magnetic resonance cholangiopancreatography (MRCP) scan showed that the right
accessory hepatic duct branching from the cystic duct dominated an anterior
segment of the right hepatic lobe. We observed the right accessory hepatic duct
using intraoperative cholangiography, and we were able to perform laparoscopic
cholecystectomy without injuring it. He had no complication after discharge, and
a drip-infusion cholangiography-computed tomography (DIC-CT) scan demonstrated
that the right accessory hepatic duct was intact, and it dominated an anterior
segment of the right hepatic lobe. During laparoscopic cholecystectomy, a bile
duct injury is the most challenging perioperative complication. We selected MRCP
preoperatively; however, if it is necessary for us to observe an anomalous
biliary tract more precisely, we recommend selecting DIC-CT endoscopic retrograde
cholangiopancreatography. Additionally, we think a bile duct injury can be
avoided with intraoperative cholangiography, even if there is an anomalous
biliary tract.
PMID- 28702165
TI - Single-stage reconstruction for buccal mucosa tumor resection including the
labial commissure using a facial artery musculomucosal flap and a vermilion
advancement flap.
AB - Resection of buccal mucosa tumors may occasionally involve the labial angle and
peripheral skin. Reconstruction is required when the resection involves more than
one-third of the lip. We describe a single-stage reconstruction using a facial
artery musculomucosal (FAMM) flap and a vermilion advancement flap after buccal
mucosa resection including the labial angle. A 62-year-old woman with carcinoma
in situ of the buccal mucosa underwent tumor resection. The resection included
the right labial angle and peripheral skin. The resection did not lead to a
massive lip defect, but a wide defect resulted on the mucosal side. The defect on
the mucosal side was reconstructed using a FAMM flap, while the vermilion defect
was covered using a vermilion advancement flap. Reconstruction performed using
the FAMM flap and vermilion advancement flap produced aesthetically and
functionally satisfactory outcomes.
PMID- 28702166
TI - Venous occlusion test applied to the tributaries of the superior mesenteric veins
of the pancreas head infiltrated by tumor.
AB - A 64-year-old white woman presented with cholestatic jaundice, weight loss and a
solid lesion in the pancreas head. At multislice computed tomography, a superior
mesenteric vein (SMV) and one of it tributaries showed signs of tumor
infiltration. At surgery, a venous occlusion test applied to the infiltrated
tributary of the SMV showed immediate venous congestion in two-thirds of the
distal small intestine. No reconstruction attempt was made due to the small size
of the vessel. A biliodigestive anastomosis and lymph node biopsy was performed.
The herein assessed case report suggests that the ileal tributary occlusion test
applied to patients presenting pancreatic adenocarcinoma, with invasion of the
tributaries of the SMV, may be effective in contraindicating resection
procedures.
PMID- 28702161
TI - Bio-collections in autism research.
AB - Autism spectrum disorder (ASD) is a group of complex neurodevelopmental disorders
with diverse clinical manifestations and symptoms. In the last 10 years, there
have been significant advances in understanding the genetic basis for ASD,
critically supported through the establishment of ASD bio-collections and
application in research. Here, we summarise a selection of major ASD bio
collections and their associated findings. Collectively, these include mapping
ASD candidate genes, assessing the nature and frequency of gene mutations and
their association with ASD clinical subgroups, insights into related molecular
pathways such as the synapses, chromatin remodelling, transcription and ASD
related brain regions. We also briefly review emerging studies on the use of
induced pluripotent stem cells (iPSCs) to potentially model ASD in culture. These
provide deeper insight into ASD progression during development and could generate
human cell models for drug screening. Finally, we provide perspectives concerning
the utilities of ASD bio-collections and limitations, and highlight
considerations in setting up a new bio-collection for ASD research.
PMID- 28702167
TI - Clostridium perfringens's necrotizing acute pancreatitis: a case of success.
AB - The authors report a case of a 62-year-old man with upper abdominal pain with few
hours of onset and vomits. The initial serum amylase was 2306 U/L. The first CT
showed signs of a non-complicated acute pancreatitis. He suffered clinical
deterioration and for this reason he was admitted on the intensive care unit
where he progressed to multiple organ failure in <24 h. A new CT scan was
performed that showed pneumoperitoneum and pneumoretroperitoneum. He underwent an
exploratory laparotomy and pancreatic necrosectomy and vacuum pack laparostomy
were performed. Intraoperative peritoneal fluid culture was positive for
Clostridium perfringens confirming the diagnosis. He was discharged from hospital
after 61 days. According to our research this is the second case reported in
literature of a spontaneous acute necrotizing pancreatitis caused by C.
perfringens, with pneumoretroperitoneum and pneumoperitoneum on evaluation by CT
scan, that survived after surgical treatment and vigorous resuscitation.
PMID- 28702168
TI - Familial spontaneous splenic rupture in a patient with idiopathic splenomegaly
report of a case.
AB - Spontaneous splenic rupture in a healthy individual is a rare phenomenon. This
article reports on a patient with an uneventful medical history, presenting with
atraumatic splenic rupture. Three family members of the patients experienced the
same in the past.
PMID- 28690831
TI - Patient waiting time in the outpatient clinic at a central surgical hospital of
Vietnam: Implications for resource allocation.
AB - Background: Patient waiting time is considered as a crucial parameter in the
assessment of healthcare quality and patients' satisfaction towards healthcare
services. Data concerning this has remained limited in Vietnam. Thus, this study
aims to assess patient waiting time in the outpatient clinic in Viet Duc Hospital
(Hanoi, Vietnam) in order to enable stakeholders to inform evidence-based
interventions to improve the quality of healthcare services. Methods: A cross
sectional study was conducted from June 2014 to June 2015 in the outpatient
clinic at Viet Duc Hospital. Waiting time stratified by years (2014 and 2015),
months of the year, weekdays, and hours of the day were extracted from Hospital
Management software and carefully calculated. Stata 12.0 was employed to analyze
data, including the average time (M+/- SD), frequencies and percentage (%).
Results: There was a total of 137,881 patients involved in the study. The average
waiting time from registration to preliminary diagnosis in 2014 was 50.41
minutes, and in 2015 was 42.05 minutes. A longer waiting time was recorded in the
morning and in those having health insurance. Conclusions: Our study highlights
the essential need for human resource promotion to reduce patient waiting time.
Also, attention should be paid to the simplification of administrative procedures
in order to reduce waiting time among insured patients.
PMID- 28690831
TI - Patient waiting time in the outpatient clinic at a central surgical hospital of
Vietnam: Implications for resource allocation.
AB - Background: Patient waiting time is considered as a crucial parameter in the
assessment of healthcare quality and patients' satisfaction towards healthcare
services. Data concerning this has remained limited in Vietnam. Thus, this study
aims to assess patient waiting time in the outpatient clinic in Viet Duc Hospital
(Hanoi, Vietnam) in order to enable stakeholders to inform evidence-based
interventions to improve the quality of healthcare services. Methods: A cross
sectional study was conducted from June 2014 to June 2015 in the outpatient
clinic at Viet Duc Hospital. Waiting time stratified by years (2014 and 2015),
months of the year, weekdays, and hours of the day were extracted from Hospital
Management software and carefully calculated. Stata 12.0 was employed to analyze
data, including the average time (M+/- SD), frequencies and percentage (%).
Results: There was a total of 137,881 patients involved in the study. The average
waiting time from registration to preliminary diagnosis in 2014 was 50.41
minutes, and in 2015 was 42.05 minutes. A longer waiting time was recorded in the
morning and in those having health insurance. Conclusions: Our results provided
evidence that despite the decrease of waiting time from 2014 to 2015, waiting
time was much higher among patients having health insurance compared to their
counterparts. The findings suggest that human resources promotion and
distribution should be emphasized in outpatient clinics and health insurance
related administrative procedures should be simplified.
PMID- 28690833
TI - Effect of PVP on the characteristic of modified membranes made from waste PET
bottles for humic acid removal.
AB - Background: The aim of the present study was to evaluate the possibility of using
recycled polymer (waste polyethylene terephthalate [PET] bottles) as a membrane
material. Furthermore, the effect of the addition of a pore-forming agent and
preparation conditions was also observed. Methods: Porous polymeric membranes
were prepared via thermally induced phase separation by dissolving recycled PET
in phenol. PET polymer was obtained from waste plastic bottles as a new source of
polymeric material. For original PET membrane, the casting solution was prepared
by dissolving of 20wt% PET in phenol solution. For PET modified membrane, a 5 wt%
of polyvinylpyrrolidone (PVP) was added into polymer solution. The solution was
cast onto a glass plate at room temperature followed by evaporation before the
solidification process. The membranes formed were characterized in terms of
morphology, chemical group, and filtration performance. A humic acid solution was
used to identify the permeability and the solute rejection of the membranes.
Results: The results showed that the recycled PET from waste plastic bottles was
applicable to use as a membrane material for a water treatment process. The
maximum flux of 97.0 l/m 2.hr was obtained from filtration test using PET
membrane. The highest rejection of humic acid in a water sample, which reached up
to 75.92%, was obtained using the PET/PVP membrane. Conclusions: The recycled PET
from waste bottles was successfully used to prepare porous membrane. The membrane
was modified by the addition of PVP as a membrane modifying agent. SEM analysis
confirmed that the original PET membrane has a rough and large pore structure.
The addition of PVP improved the pore density with a narrow pore structure. The
PET/PVP membrane conditioned with evaporation was the best in humic acid
rejection.
PMID- 28702173
TI - Surveillance of antimicrobial consumption: methodological review for systems
development in Thailand.
PMID- 28702174
TI - Costs of implementing integrated community case management (iCCM) in six African
countries: implications for sustainability.
AB - BACKGROUND: Sub-Saharan Africa still reports the highest rates of under-five
mortality. Low cost, high impact interventions exist, however poor access remains
a challenge. Integrated community case management (iCCM) was introduced to
improve access to essential services for children 2-59 months through diagnosis,
treatment and referral services by community health workers for malaria,
pneumonia and diarrhea. This paper presents the results of an economic analysis
of iCCM implementation in regions supported by UNICEF in six countries and
assesses country-level scale-up implications. The paper focuses on costs to
provider (health system and donors) to inform planning and budgeting, and does
not cover cost-effectiveness. METHODS: The analysis combines annualised set-up
costs and 1 year implementation costs to calculate incremental economic and
financial costs per treatment from a provider perspective. Affordability is
assessed by calculating the per capita financial cost of the program as a
percentage of the public health expenditure per capita. Time and financial
implications of a 30% increase in utilization were modeled. Country scale-up is
modeled for all children under 5 in rural areas. RESULTS: Utilization of iCCM
services varied from 0.05 treatment/y/under-five in Ethiopia to over 1 in Niger.
There were between 10 and 603 treatments/community health worker (CHW)/y.
Consultation cost represented between 93% and 22% of economic costs per treatment
influenced by the level of utilization. Weighted economic cost per treatment
ranged from US$ 13 (2015 USD) in Ghana to US$ 2 in Malawi. CHWs spent from 1 to 9
hours a week on iCCM. A 30% increase in utilization would add up to 2 hours a
week, but reduce cost per treatment (by 20% in countries with low utilization).
Country scale up would amount to under US$ 0.8 per capita total population (US$
0.06-US$0.74), between 0.5% and 2% of public health expenditure per capita but 8%
in Niger. CONCLUSIONS: iCCM addresses unmet needs and impacts on under 5
mortality. An economic cost of under US$ 1/capita/y represents a sound
investment. Utilization remains low however, and strategies must be developed as
a priority to improve demand. Continued donor support is required to sustain iCCM
services and strengthen its integration within national health systems.
PMID- 28702175
TI - Costs of hospitalization with respiratory syncytial virus illness among children
aged <5 years and the financial impact on households in Bangladesh, 2010.
AB - BACKGROUND: Respiratory syncytial virus (RSV) is the leading cause of acute
respiratory illness in young children and results in significant economic burden.
There is no vaccine to prevent RSV illness but a number of vaccines are in
development. We conducted this study to estimate the costs of severe RSV illness
requiring hospitalization among children <5 years and associated financial impact
on households in Bangladesh. Data of this study could be useful for RSV vaccine
development and also the value of various preventive strategies, including use of
an RSV vaccine in children if one becomes available. METHODS: From May through
October 2010, children aged <5 years with laboratory-confirmed RSV were
identified from a sentinel influenza program database at four tertiary hospitals.
Research assistants visited case-patients' homes after hospital discharge and
administered a structured questionnaire to record direct medical costs (physician
consultation fee, costs for hospital bed, medicines and diagnostic tests); non
medical costs (costs for food, lodging and transportation); indirect costs
(caregivers' productivity loss), and coping strategies used by families to pay
for treatment. We used WHO-Choice estimates for routine health care service
costs. We added direct, indirect and health care service costs to calculate cost
per-episode of severe RSV illness. We used Monte Carlo simulation to estimate
annual economic burden for severe RSV illness. FINDINGS: We interviewed
caregivers of 39 persons hospitalized for RSV illness. The median direct cost for
hospitalization was US$ 62 (interquartile range [IQR] = 43-101), indirect cost
was US$ 19 (IQR = 11-29) and total cost was US$ 94 (IQR = 67-127). The median out
of-pocket cost was 24% of monthly household income of affected families (US$
143), and >50% families borrowed money to meet treatment cost. We estimated that
the median direct cost of RSV-associated hospitalization in children aged <5
years in Bangladesh was US$ 10 million (IQR: US$ 7-16 million), the median
indirect cost was US$ 3.0 million (IQR: 2-5 million) in 2010. CONCLUSION: RSV
associated hospitalization among children aged <5 years represents a substantial
economic burden in Bangladesh. Affected families frequently incurred considerable
out of pocket and indirect costs for treatment that resulted in financial
hardship.
PMID- 28702176
TI - Monitoring and evaluating the adherence to a complementary food supplement (Ying
Yang Bao) among young children in rural Qinghai, China: a mixed methods
evaluation study.
AB - BACKGROUND: Large investments are currently made in community-based complementary
food supplement (Ying Yang Bao, YYB) programs to improve nutrition of young
children in rural areas in China. However, there is a lack of knowledge about the
experience and challenges of implementing YYB programs in China. We aimed to: 1)
monitor distribution of YYB; 2) assess children's adherence to and acceptability
of YYB; and 3) evaluate community-based strategies to improve the program.
METHODS: This mixed methods evaluation study combined data from surveys and focus
groups that took place during a controlled interventional evaluation trial. The
trial aimed to evaluate the effectiveness of community-based YYB distribution on
improving children's health status in rural areas in China. We conducted five
cross-sectional surveys with caregivers of children aged 6-23 months (baseline
survey (N = 1804) in August 2012 and four follow-up cross-sectional surveys: 1) N
= 494 in January 2013; 2) N = 2187 in August 2013; 3) N = 504 in January 2014;
and 4) N = 2186 in August 2014) in one rural county in Qinghai Province. We used
a two-stage cluster sampling technique to select mothers with eligible children
for each survey. Information was collected from caregivers on household
characteristics, YYB consumption and acceptability in the surveys. High adherence
in each survey was defined as children who consumed at least four YYB sachets
during the previous week. A logistic regression model was developed to obtain
odds ratios (OR) with 95% confidence intervals of factors associated with high
adherence. Also, we conducted 10 focus groups with73 caregivers and health
workers involved in the YYB distribution. Content analysis was used to explore
qualitative findings, which were used to gain deeper insight into the
quantitative results. RESULTS: Around 90% of caregivers had ever received YYB and
more than 80% of children ever took YYB. Caregivers mainly knew about YYB through
their village doctors. High adherence to YYB increased from 49.4% in the first
follow-up survey (January 2013) to 81.4% in the last follow-up survey (August
2014; P < 0.0001). Repeated training sessions with village doctors could increase
adherence. However, due to unplanned YYB stock-out, caregivers did not receive
YYB for six months, which may have led to a decrease of high adherence from 64.1%
in the second follow-up survey (August 2013) to 53.6% in the third follow-up
survey (January 2014; P < 0.0001). Self-reported acceptability increased from
43.2% to 71.8%, partly due to improving the taste of YYB, which was the main
reason that children disliked taking YYB. Unfortunately, more than 60% of
caregivers did not perceive positive health improvement in their children after
taking YYB. Multivariate analysis showed that children with diarrhea (OR = 1.216,
95% CI 1.025-1.442), cough or fever (OR = 1.222, 95% CI 1.072-1.393) during the
past two weeks had significantly lower adherence. CONCLUSIONS: This evaluation
study showed that program monitoring in rural West China was critically important
for understanding program implementation and adherence trends. This led to
strategic changes to the intervention over time: improving the taste of YYB;
strengthening health education of village doctors and caregivers; and ensuring
continuity of YYB supply. Future programs need to monitor program implementation
in other settings in China and elsewhere.
PMID- 28702177
TI - Socioeconomic status and prevalence of type 2 diabetes in mainland China, Hong
Kong and Taiwan: a systematic review.
AB - BACKGROUND: China is estimated to have had the largest number of people with
diabetes in the world in 2015, with extrapolation of existing data suggesting
that this situation will continue until at least 2030. Type 2 diabetes has been
reported to be more prevalent among people with low socioeconomic status (SES) in
high-income countries, whereas the opposite pattern has been found in studies
from low- and middle-income countries. We conducted a systematic review to
describe the cross-sectional association between SES and prevalence of type 2
diabetes in Chinese in mainland China, Hong Kong and Taiwan. METHODS: We
conducted a systematic literature search in Medline, Embase and Global Health
electronic databases for English language studies reporting prevalence or odds
ratio for type 2 diabetes in a Chinese population for different SES groups
measured by education, income and occupation. We appraised the quality of
included studies using a modified Newcastle-Ottawa Scale. Heterogeneity of
studies precluded meta-analyses, therefore we summarized study results using a
narrative synthesis. RESULTS: Thirty-three studies met the inclusion criteria and
were included in the systematic review. The association between education, income
and occupation and type 2 diabetes was reported by 27, 19 and 12 studies,
respectively. Most, but not all, studies reported an inverse association between
education and type 2 diabetes, with odds ratios (OR) and 95% confidence interval
(CI) ranging from 0.39 (CI not reported) to 1.52 (95% CI 0.91 - 2.54) for the
highest compared to the lowest education level. The association between income
and type 2 diabetes was inconsistent between studies. Only a small number of
studies identified a significant association between occupation and type 2
diabetes. Retired people and people working in white collar jobs were reported to
have a higher risk of type 2 diabetes than other occupational groups even after
adjusting for age. CONCLUSIONS: This first systematic review of the association
between individual SES and prevalence of type 2 diabetes in China found that low
education is probably associated with an increased prevalence of type 2 diabetes,
while the association between income and occupation and type 2 diabetes is
unclear.
PMID- 28702178
TI - The development prospection of HDAC inhibitors as a potential therapeutic
direction in Alzheimer's disease.
AB - Alzheimer's disease (AD) is a chronic neurodegenerative disease, which is
associated with learning and memory impairment in the elderly. Recent studies
have found that treating AD in the way of chromatin remodeling via histone
acetylation is a promising therapeutic regimen. In a number of recent studies,
inhibitors of histone deacetylase (HDACs) have been found to be a novel promising
therapeutic agents for neurological disorders, particularly for AD and other
neurodegenerative diseases. Although HDAC inhibitors have the ability to
ameliorate cognitive impairment, successful treatments in the classic AD animal
model are rarely translated into clinical trials. As for the reduction of
unwanted side effects, the development of HDAC inhibitors with increased isoform
selectivity or seeking other directions is a key issue that needs to be
addressed. The review focused on literatures on epigenetic mechanisms in recent
years, especially on histone acetylation in terms of the enhancement of
specificity, efficacy and avoiding side effects for treating AD.
PMID- 28702180
TI - Abdominal perineal resection or wilde local excision in primary anorectal
malignant melanoma. Case report and review.
AB - INTRODUCTION: Primary anorectal malignant melanoma is a rare and aggressive tumor
that carries a poor prognosis. Anorectal melanoma (ARM) is often misdiagnosed as
hemorrhoids adenocarcinoma polips and rectal cancer. ARM spreads along sub
mucosal planes and is often to wide-spread for complete resection at time of
diagnosis and almost all patients die because of metastases. PRESENTATION OF THE
CASE: A 77-year-old male patient presented a history of recurrent rectal bleeding
and whose histopathological diagnosis was melanoma. DISCUSSION: The treatment of
choice remains controversial. Surgery with complete resection represents the
typical treatment. However standard operative procedures related to the area of
resection and lymph dissection have yet to be established. Abdominal perineal
resection (APR) with or without bilateral inguinal lymphadenectomy or wide local
excision (WLE) have been used to manage patients with ARM. CONCLUSION: The higher
serum levels of LDH and YKL-40 are suggestive for Anorectal Melanoma diagnosis.
The decrease of these findings may be associated with good prognosis. The review
of both APR and WLE options suggests no significant difference in survival among
patients.
PMID- 28702179
TI - Pathological correlations between traumatic brain injury and chronic
neurodegenerative diseases.
AB - Traumatic brain injury is among the most common causes of death and disability in
youth and young adults. In addition to the acute risk of morbidity with moderate
to severe injuries, traumatic brain injury is associated with a number of chronic
neurological and neuropsychiatric sequelae including neurodegenerative diseases
such as Alzheimer's disease and Parkinson's disease. However, despite the high
incidence of traumatic brain injuries and the established clinical correlation
with neurodegeneration, the causative factors linking these processes have not
yet been fully elucidated. Apart from removal from activity, few, if any
prophylactic treatments against post-traumatic brain injury neurodegeneration
exist. Therefore, it is imperative to understand the pathophysiological
mechanisms of traumatic brain injury and neurodegeneration in order to identify
potential factors that initiate neurodegenerative processes. Oxidative stress,
neuroinflammation, and glutamatergic excitotoxicity have previously been
implicated in both secondary brain injury and neurodegeneration. In particular,
reactive oxygen species appear to be key in mediating molecular insult in
neuroinflammation and excitotoxicity. As such, it is likely that post injury
oxidative stress is a key mechanism which links traumatic brain injury to
increased risk of neurodegeneration. Consequently, reactive oxygen species and
their subsequent byproducts may serve as novel fluid markers for identification
and monitoring of cellular damage. Furthermore, these reactive species may
further serve as a suitable therapeutic target to reduce the risk of post-injury
neurodegeneration and provide long term quality of life improvements for those
suffering from traumatic brain injury.
PMID- 28702181
TI - The major thoracic vascular invasion of lung cancer.
AB - BACKGROUND: We actually investigated the surgical and pathological findings in
cases which tumor invasion of the major thoracic vessels was suspected based on
the preoperative Computed tomography (CT) findings. MATERIALS AND METHODS: We
retrospectively reviewed our prospective database of all patients, who underwent
lung resection for lung cancer from 2012 to 2014. 387 patients underwent lung
cancer surgery. Among these patients, we analyzed 30 patients in whom pulmonary
artery (PA) invasion was suspected and 11 patients in whom pulmonary vein (PV) or
left atrium (LA) invasion was suspected based on the preoperative CT findings.
RESULTS: Among the 30 patients with suspected PA invasion, there were 9 patients
in whom the tumor could be peeled off the PA in actual thoracotomy. Pathological
invasion of the PA was observed in 6 of these patients. The positive predictive
value of the preoperative CT findings was 20%. Among the 11 patients with
suspected PV or LA invasion, there were 2 patients in whom the tumor could be
peeled off the PV or LA in actual thoracotomy. Pathological tumor invasion of the
PV or LA was observed in 4 of these patients. The positive predictive value of
the preoperative CT findings was 36%. CONCLUSION: The positive predictive value
of the preoperative CT findings for tumor invasion of the thoracic vessels was
low. Therefore, surgical opportunities that offer the chance of a cure shouldn't
be missed in advanced lung cancer patients because the tumor is located near the
major thoracic vessels on preoperative CT.
PMID- 28702182
TI - Effect of adjuvant chemotherapy after pulmonary metastasectomy on the prognosis
of colorectal cancer.
AB - BACKGROUND: Adjuvant chemotherapy after resection of colorectal cancer (CRC) lung
metastases may reduce recurrences and improve survival. We investigated the
effects of adjuvant chemotherapy after curative resection of lung CRC metastases
on prognosis. METHODS: We retrospectively reviewed records of our patients
undergoing pulmonary metastasectomy from CRC between January 2000-March 2014.
Data were analyzed with Kaplan-Meier survival analysis and Cox proportional
hazards models. RESULTS: One-hundred (56 men; median age, 66 years) of 128
consecutive patients who underwent complete resection for first lung colorectal
metastases were analyzed. Postoperative 5-year rates of overall survival (OS) and
relapse-free survival (RFS) were 76% and 41%, respectively. Adjuvant chemotherapy
strongly affected RFS and OS by multivariable analysis compared to surgery alone
(RFS: HR, 0.49; 95% CI, 0.27-0.88; P = 0.016 and OS: HR, 0.35; 95% CI, 0.14-0.81;
P = 0.014). Similar effects of adjuvant chemotherapy occurred in subgroups
respectively classified according to number of lung metastases and preoperative
serum carcinoembryonic antigen (CEA) level. CONCLUSIONS: Adjuvant chemotherapy
after curative resection of lung metastases might strongly affect the prognosis
of metastatic CRC patients. Even patients with single metastatic lesions and
normal preoperative CEA level appeared to receive benefits from such
chemotherapy. Narrowing of suitable candidates by predicting the effects of
systemic chemotherapy and prospective randomized studies are needed.
PMID- 28702183
TI - Induction of autoimmune abdominal aortic aneurysm in pigs - A novel large animal
model.
AB - BACKGROUND: Abdominal aortic aneurysm (AAA) is a common disease with a high
mortality. Many animal models have been developed to further understand the
pathogenesis of the disease, but no large animal model has been developed to
investigate the autoimmune aspect of AAA formation. The aim of this study was to
develop a large animal model for abdominal aortic aneurysm induction through
autoimmunity by performing sheep-to-pig xenotransplantation. METHODS: Six pigs
underwent a xenotransplantation procedure where the infrarenal porcine aorta was
replaced by a decellularized sheep aorta. In the following 47 days, the AP
diameter of the xenografts was measured using ultrasound once a week. All
xenografts were harvested for histological analyses. RESULTS: All the xenografts
formed aneurysms with a mean increase in AP-diameter of 80.98 +/- 30.20% (p <
0.005). The ultrasound measurements demonstrated a progressive aneurysmal
expansion with no sign of halting towards the end of the follow-up period.
Histology showed destruction of tunica media and the elastic tissue, neointimal
hyperplasia, adventitial thickening with neovascularization, infiltration of
lymphocytes and granulocytes, and in some cases intramural haemorrhaging.
CONCLUSION: We developed a novel large animal AAA model by infrarenal aortic
sheep-to-pig xenograph transplantation resulting in autoimmune AAA induction with
continuously progressive aneurysmal growth. This model can be used to provide a
better understand the autoimmune aspect of AAA formation in large animals.
PMID- 28702184
TI - Maxillary artery based flaps for oral cavity reconstruction, a review.
AB - BACKGROUND: There are different flaps based on the branches of the maxillary
artery. Flaps based on the maxillary artery branches can be used for oral cavity
reconstruction in selected cases, but there is lack of comprehensive review in
this topic. METHODS: A literature review was performed on Medline for maxillary
artery based flaps and oral cavity reconstruction. Surgical techniques for each
possible variant of maxillary artery based flaps and an example of each situation
for oral cavity reconstruction is explained. RESULT: Five variants of soft tissue
flaps based on maxillary artery branches are presented. Some of them such as
temporal flap, superiorly based masseter flap, palatal flap and posteriorly based
buccinator myomucosal flap are famous flaps, while posteriorly based inferior
turbinate flap is less noticed for oral cavity reconstruction. Nasoseptal and
infraorbital based flaps are two other maxillary artery based flaps but have no
role in oral cavity reconstruction. CONCLUSION: Maxillary artery based flaps
should be considered as an option especially in previously
radiotherapy/surgically operated patients with facial vessels sacrifice.
PMID- 28702185
TI - Potential cost savings by minimisation of blood sample delays on care decision
making in urgent care services.
AB - BACKGROUND: Timely availability of blood sample results for interpretation
affects planning and delivery of patient care from initial assessment in Accident
and Emergency (A&E) departments. MATERIALS AND METHODS: Rates of, and reasons
for, rejected blood samples submitted from all clinical areas over one month were
evaluated. Haemoglobin (Hb) represented haematology and potassium (K+),
biochemistry. A prospective observational study evaluated the methodology of
sample collection and impact on utility. RESULTS: 16,061 haematology and 16,209
biochemistry samples were evaluated; 1.4% (n = 229, range 0.5-7.3%) and 4.7% (n =
762, range 0.9-14%) respectively were rejected, with 14% (n = 248/1808) K+
rejection rate in A&E. Patients with rejected K+ and Hb had a longer median in
hospital stay of 9 and 76 h respectively and additional stay fixed costs of
L26,824.74 excluding treatment. The rejection rate with Vacutainer and butterfly
(4.0%) was lower than Vacutainer and cannula (28%). CONCLUSION: Sample rejection
rate is high and is associated with increased in-hospital stay and cost. Blood
sampling technique impacts on rejection rates. Reduction in sample rejection
rates in emergency care areas in acute hospitals has the potential to impact on
patient flow and reduce cost.
PMID- 28702186
TI - The biological and clinical basis for the use of adipose-derived stem cells in
the field of wound healing.
AB - Worldwide, hard-to-heal lower limb wounds are estimated to affect 1.5-3% of the
adult population with a treatment-related annual cost of $10 billion. Thus,
chronic skin ulcers of the lower limb are a matter of economic and public
concern. Over the years, multiple medical and surgical approaches have been
proposed but they are still inadequate, and no effective therapy yet exists.
Regenerative medicine and stem cell-based therapies hold great promise for wound
healing. Recently, many plastic surgeons have studied the potential clinical
application of adipose-derived stem cells (ASCs), which are a readily available
adult stem cell population that can undergo multilineage differentiation and
secrete growth factors that can enhance wound-healing processes by promoting
angiogenesis, and hence increase local blood supply. ASCs have been widely
studied in vitro and in vivo in animal models. However, there are few randomized
clinical trials on humans, and these are still ongoing or recruiting patients.
Moreover, there is no consensus on a common isolation protocol that is clinically
feasible and which would ensure reproducible results. The authors aim to provide
readers with an overview of the biological properties of ASCs as well as their
clinical application, to help better understanding of present and future
strategies for the treatment of hard-to-heal wounds by means of stem cell-based
therapies.
PMID- 28702188
TI - New method of indocyanine green fluorescence sentinel node mapping for early
gastric cancer.
AB - BACKGROUND: The present study describes the retrospective feasibility study of
ICG fluorescence SN mapping in back-table for early gastric cancer using
PINPOINT(r). METHOD: SN mapping were performed as following; the day before
surgery, 0.5 ml ICG was injected endoscopically in four quadrants of the
submucosa surrounding the gastric cancer using an endoscopic puncture.
Intraoperatively, the gastrocolic ligament was divided to visualize all possible
directions of lymphatic flow from the stomach. PINPOINT(r) (NOVADAQ, Canada) was
used to illuminate regional lymph nodes from the serosal side. Positive staining
was confirmed by at least 3 surgeons and an endoscopist during surgery (Figure
1). Lymph node dissection and gastrectomy were performed according to the
criteria of gastric cancer treatment guidelines of JGCA. RESULT: All 6 patients
had gastrectomy with laparoscopic approach. ICG positive lymphatic flow and lymph
nodes were able to be observed in all the patients. Final pathological diagnosis
was all StageI and curative resection. All the patients had ICG positive
lymphatic area in left gastric artery (LGA) area. Two patients with tumor located
in L area had ICG positive flow to right gastroepipoloic artery (RGEA) area. The
mean of ICG positive lymph nodes was 8.6. One patient had a metastatic lymph node
in station No.4, which was positive for ICG. CONCLUSION: Our method made
identification of ICG positive lymph nodes easy in SN mapping in back-table under
room light. Although further accumulation and analysis are necessary, we may be
able to apply this method for intraoperative SN mapping of laparoscopic gastric
cancer surgey.
PMID- 28702187
TI - Procedure, applications, and outcomes of autologous fat grafting.
AB - OBJECTIVE: To systematically review the procedure, applications, and outcomes of
autologous fat grafting, a promising technique with various clinical
applications. PATIENTS AND METHODS: Literature review of publications concerning
autologous fat grafting. RESULTS: Since its introduction, lipofilling has become
increasingly popular; however, its results are variable and unpredictable.
Several modifications have been made to the procedures of fat harvesting,
processing, and injecting. Surgical excision and low negative-pressure aspiration
with large-bore cannulas minimize adipocyte damage during fat harvesting. The
"wet" method of fat harvesting involves fluid injection at the donor site and
facilitates lipoaspiration while minimizing pain and ecchymosis. For fat
processing, centrifugation at a low speed is preferable to high-speed
centrifugation, gravity separation or filtration. Fat injection at the recipient
site should be performed using small-gauge cannulas in a fanning out pattern over
multiple sessions, rather than a single session. Fat grafts exhibit not only
dermal filler properties but also regenerative potential owing to the presence of
stem cells in fat tissue. Thus, the clinical applications of autologous fat
grafting include correction of secondary contour defects after breast
reconstruction, release of painful scar contractures, and treatment of burn scars
and radiodermatitis. Lipofilling is also used in aesthetic surgery, such as
facial and hand rejuvenation, augmentation rhinoplasty, and breast and gluteal
augmentation. The complications of lipofilling are minimal and include bruising,
swelling, pain, infection, necrosis, and calcification. CONCLUSIONS: Lipofilling
is a low-risk procedure that can be used to correct soft-tissue defects in the
face, trunk, and extremities, with minimal discomfort for patients.
PMID- 28702189
TI - A case report of pneumo-retro-peritoneum: An unusual presentation of ischio
rectal abscess.
AB - INTRODUCTION: Ano-rectal abscesses are common. They however usually do not
present with abdominal symptoms. CT although useful is not routinely carried out.
Finding of Pneumo-retro-peritoneum with ischio-rectal abscess is rare. CASE
PRESENTATION: We present the case of a diabetic gentleman who presented with
abdominal pain and distension and was found to have ischio-rectal abscess on
perianal examination. Although initially suspected to have acute abdomen due to
perforated viscus, CT scan revealed pneumo-retro-peritoneum which appeared to
arise due to the abscess. Patient underwent incision and drainage of the abscess
followed by serial debridement. He made a complete recovery. CONCLUSION:
Abdominal symptoms are rare in ischio-rectal abscess, but they must be kept in
mind. Proper diagnosis may avoid a negative laparotomy.
PMID- 28702190
TI - Impact of dietary l-arginine supply during early gestation on myofiber
development in newborn pigs exposed to intra-uterine crowding.
PMID- 28702191
TI - Regularized quantile regression for SNP marker estimation of pig growth curves.
AB - BACKGROUND: Genomic growth curves are generally defined only in terms of
population mean; an alternative approach that has not yet been exploited in
genomic analyses of growth curves is the Quantile Regression (QR). This
methodology allows for the estimation of marker effects at different levels of
the variable of interest. We aimed to propose and evaluate a regularized quantile
regression for SNP marker effect estimation of pig growth curves, as well as to
identify the chromosome regions of the most relevant markers and to estimate the
genetic individual weight trajectory over time (genomic growth curve) under
different quantiles (levels). RESULTS: The regularized quantile regression (RQR)
enabled the discovery, at different levels of interest (quantiles), of the most
relevant markers allowing for the identification of QTL regions. We found the
same relevant markers simultaneously affecting different growth curve parameters
(mature weight and maturity rate): two (ALGA0096701 and ALGA0029483) for
RQR(0.2), one (ALGA0096701) for RQR(0.5), and one (ALGA0003761) for RQR(0.8).
Three average genomic growth curves were obtained and the behavior was explained
by the curve in quantile 0.2, which differed from the others. CONCLUSIONS: RQR
allowed for the construction of genomic growth curves, which is the key to
identifying and selecting the most desirable animals for breeding purposes.
Furthermore, the proposed model enabled us to find, at different levels of
interest (quantiles), the most relevant markers for each trait (growth curve
parameter estimates) and their respective chromosomal positions (identification
of new QTL regions for growth curves in pigs). These markers can be exploited
under the context of marker assisted selection while aiming to change the shape
of pig growth curves.
PMID- 28702192
TI - Freezing of gait is an early clinical feature of progressive supranuclear palsy.
AB - BACKGROUND AND AIM: Early clinical diagnosis of progressive supranuclear palsy
(PSP) remains challenging. AIM: We attempted to identify any sign or symptom to
diagnose PSP earlier. METHODS: A total of 401 patients, 40 with PSP and 361 with
other neurodegenerative disorders, were included. We followed these patients for
at least 1 year since 2009. We reviewed the signs and symptoms of patients with
PSP in a standardized manner, and observed four manifestations: "vertical
supranuclear gaze abnormality," "movement disorders," "pseudobulbar palsy" and
"dementia of frontal type." Features, such as symmetric parkinsonism, freezing of
gait, postural instability, dysarthria and/or dysphagia, or dementia of frontal
type, were considered core clinical features. RESULTS: In patients with PSP,
"movement disorders" was the most common manifestation, whereas "vertical
supranuclear gaze abnormality" was uncommon during the early disease course. A
total of 16 patients fulfilled the National Institute for Neurological Disorders
and Stroke and Society for PSP criteria for possible PSP at their first clinic
visit. Of the remaining 24 patients, 15 presented with one or more core clinical
features before fulfilling the criteria for possible PSP; nine patients had a
clinical diagnosis of PSP but never fulfilled the criteria. A total of 49 of the
361 patients with other neurodegenerative disorders had core clinical features. A
comparison showed that freezing of gait differentiated the groups the best over
the disease course. CONCLUSION: Freezing of gait is an early feature that might
improve the clinical diagnosis of PSP, whereas vertical supranuclear gaze
abnormality is not.
PMID- 28702193
TI - Update on the first-line treatment for Helicobacter pylori infection - a
continuing challenge from an old enemy.
AB - Because the prevalence of antibiotic resistance markedly increases with time
worldwide, anti-H. pylori treatment is continuing to be a great challenge
forsphysicians in clinical practice. The Real-world Practice & Expectation of
Asia-Pacific Physicians and Patients in Helicobacter Pylori Eradication (REAP-HP)
Survey demonstrated that the accepted minimal eradication rate of anti-H. pylori
regimen in H. pylori-infected patients was 91%. The Kyoto Consensus Report on
Helicobacter Pylori Gastritis also recommended that, within any region, only
regimens which reliably produce eradication rates of >=90% in that population
should be used for empirical treatment. This article is aimed to review current
first-line eradication regimens with a per-protocol eradication rate exceeding
90% in most geographic areas. In regions with low (?15%) clarithromycin
resistance, 14-day hybrid (or reverse hybrid), 10 ~ 14-day sequential, 7 ~ 14-day
concomitant, 10 ~ 14-day bismuth quadruple or 14-day triple therapy can achieve a
high eradication rate in the first-line treatment of H. pylori infection.
However, in areas with high (>15%) clarithromycin resistance, standard triple
therapy should be abandoned because of low eradication efficacy, and 14-day
hybrid (or reverse hybrid), 10 ~ 14-day concomitant or 10 ~ 14-day bismuth
quadruple therapy are the recommended regimens. If no recent data of local
antibiotic resistances of H. pylori strains are available, universal high
efficacy regimens such as 14-day hybrid (or reverse hybrid), concomitant or
bismuth quadruple therapy can be adopted to meet the recommendation of consensus
report and patients' expectation.
PMID- 28702194
TI - Elevation of brain-enriched miRNAs in cerebrospinal fluid of patients with acute
ischemic stroke.
AB - BACKGROUND: The purpose of this study was to investigate the potential of
cerebrospinal fluid miRNAs as diagnostic biomarkers of acute ischemic stroke
using three different profiling techniques in order to identify and bypass any
influence from technical variation. METHODS: Cerebrospinal fluid (CSF) from
patients with acute ischemic stroke (n = 21) and controls (n = 21) was collected
by lumbar puncture. miRNA analysis was performed with three different methods: 1)
Trizol RNA extraction followed by Illumina Next Generation Sequencing (NGS) on
all small RNAs, 2) Exiqon RNA extraction protocol and miRNA qPCR assays, and 3)
validation of 24 selected miRNAs with Norgen Biotek RNA extraction protocol and
Applied Biosystems qPCR assays. RESULTS: NGS detected 71 frequently expressed
miRNAs in CSF of which brain-enriched miR-9-5p and miR-128-3p were significantly
higher in CSF of stroke patients compared to controls. When dividing stroke
patients into groups according to infarct size several brain-enriched miRNAs (miR
9-5p, miR-9-3p, miR-124-3p, and miR-128-3p) were elevated in patients with
infarcts >2 cm3. This trend appeared in data from both NGS, qPCR (Exiqon), and
qPCR (Applied Biosystems) but was only statistically significant in some of the
measurement platforms. CONCLUSIONS: Several brain-enriched miRNAs are elevated in
the CSF three days after stroke onset, suggesting that these miRNAs reflect the
brain damage caused by ischemia. The expression differences seem, however,
limited to patients with larger ischemic brain injury, which argues against the
use of CSF miRNAs as diagnostic biomarkers of stroke based on current methods.
PMID- 28702195
TI - Molecular indices of viral disease development in wild migrating salmon?.
AB - Infectious diseases can impact the physiological performance of individuals,
including their mobility, visual acuity, behavior and tolerance and ability to
effectively respond to additional stressors. These physiological effects can
influence competitiveness, social hierarchy, habitat usage, migratory behavior
and risk to predation, and in some circumstances, viability of populations. While
there are multiple means of detecting infectious agents (microscopy, culture,
molecular assays), the detection of infectious diseases in wild populations in
circumstances where mortality is not observable can be difficult. Moreover, if
infection-related physiological compromise leaves individuals vulnerable to
predation, it may be rare to observe wildlife in a late stage of disease.
Diagnostic technologies designed to diagnose cause of death are not always
sensitive enough to detect early stages of disease development in live-sampled
organisms. Sensitive technologies that can differentiate agent carrier states
from active disease states are required to demonstrate impacts of infectious
diseases in wild populations. We present the discovery and validation of salmon
host transcriptional biomarkers capable of distinguishing fish in an active viral
disease state [viral disease development (VDD)] from those carrying a latent
viral infection, and viral versus bacterial disease states. Biomarker discovery
was conducted through meta-analysis of published and in-house microarray data,
and validation performed on independent datasets including disease challenge
studies and farmed salmon diagnosed with various viral, bacterial and parasitic
diseases. We demonstrate that the VDD biomarker panel is predictive of disease
development across RNA-viral species, salmon species and salmon tissues, and can
recognize a viral disease state in wild-migrating salmon. Moreover, we show that
there is considerable overlap in the biomarkers resolved in our study in salmon
with those based on similar human viral influenza research, suggesting a highly
conserved suite of host genes associated with viral disease that may be
applicable across a broad range of vertebrate taxa.
PMID- 28702196
TI - The nocturnal acoustical intensity of the intensive care environment: an
observational study.
AB - BACKGROUND: The intensive care unit (ICU) environment exposes patients to noise
levels that may result in substantial sleep disruption. There is a need to
accurately describe the intensity pattern and source of noise in the ICU in order
to develop effective sound abatement strategies. The objectives of this study
were to determine nocturnal noise levels and their variability and the related
sources of noise within an Australian tertiary ICU. METHODS: An observational
cross-sectional study was conducted in a 24-bed open-plan ICU. Sound levels were
recorded overnight during three nights at 5-s epochs using Extech (SDL 600) sound
monitors. Noise sources were concurrently logged by two research assistants.
RESULTS: The mean recorded ambient noise level in the ICU was 52.85 decibels (dB)
(standard deviation (SD) 5.89), with a maximum noise recording at 98.3 dB (A).
All recorded measurements exceeded the WHO recommendations. Noise variability per
minute ranged from 9.9 to 44 dB (A), with peak noise levels >70 dB (A) occurring
10 times/hour (SD 11.4). Staff were identified as the most common source
accounting for 35% of all noise. Mean noise levels in single-patient rooms
compared with open-bed areas were 53.5 vs 53 dB (p = 0.37), respectively.
CONCLUSION: Mean noise levels exceeded those recommended by the WHO resulting in
an acoustical intensity of 193 times greater than the recommended and
demonstrated a high degree of unpredictable variability, with the primary noise
sources coming from staff conversations. The lack of protective effects of single
rooms and the contributing effects that staffs have on noise levels are important
factors when considering sound abatement strategies.
PMID- 28702197
TI - Usefulness of plasminogen activator inhibitor-1 as a predictive marker of
mortality in sepsis.
AB - BACKGROUND: Sepsis is one of the most significant causes of mortality in
intensive care units. It indicates crosstalk between inflammation and
coagulation. In this study, we aimed to identify prognostic markers among sepsis
biomarkers and coagulation/fibrinolysis markers. METHODS: Patients with sepsis
according to the Sepsis-3 criteria were enrolled from January 2013 to September
2015. Univariate and multivariate logistic regression analyses were performed to
identify an independent predictive marker of 28-day mortality among sepsis
biomarkers and coagulation/fibrinolysis markers on ICU admission. Receiver
operating characteristic analysis was performed; the optimal cutoff value of 28
day mortality was calculated using the predictive marker. Patients were
classified into two groups according to the cutoff level of the predictive
marker. Patient characteristics were compared between the groups. RESULTS: A
total of 186 patients were enrolled in this study; the 28-day mortality was 19.4%
(36/186). PAI-1 was identified as the only independent predictive marker of 28
day mortality by univariate and multivariate logistic regression. The area under
the curve was 0.72; the optimal cutoff level was 83 ng/ml (sensitivity, 75%;
specificity, 61%). Patients were classified into a higher group (PAI-1 level >=83
ng/ml; n = 85) and a lower group (PAI-1 level <83 ng/ml; n = 101). All
disseminated intravascular coagulation (DIC) scores and Sequential Organ Failure
Assessment score were significantly higher in the higher group than in the lower
group. CONCLUSIONS: PAI-1 can predict prognosis in sepsis patients. PAI-1
reflects DIC with suppressed fibrinolysis and organ failure, with microthrombi
leading to microcirculatory dysfunction.
PMID- 28702198
TI - Paenibacillus spp. isolated from human and environmental samples in Spain:
detection of 11 new species.
AB - One hundred thirty-six isolates, 88 human and 48 environmental, that met the
requirements to belong to the genus Paenibacillus were identified using a
polyphasic taxonomic approach known as 16S rRNA plus phenotypic traits. Thirty
seven Paenibacillus species were identified; some had not been previously
reported from clinical samples. The main species were P. pabuli (13 isolates), P.
provencensis (11), P. phoenicis (9) and P. lautus (8). P. pabuli (11/13) and P.
provencensis (8/11) were mainly environmental isolates, while P. phoenicis (9/9)
and P. lautus (6/8) were mainly human isolates. Despite the difficulties in
assigning to human Paenibacillus isolates a role as a pathogen or contaminant,
here 25% of the isolates were involved in true infections, especially in those
cases that affected abscesses, wound exudates, ocular infections and diverse
fluids. In addition, 15 isolates were identified as 11 'Candidatus' to a new
species, all of them from human specimens except one that was obtained from
laboratory air. The antimicrobial susceptibility testing showed 95.6% of isolates
were resistant to ampicillin, 44% were resistant to cotrimoxazole, 20 to 30% were
resistant to cefotaxime and vancomycin and 13% were resistant to rifampicin and
erythromycin.
PMID- 28702199
TI - Prevalence of methicillin resistance and macrolide-lincosamide-streptogramin B
resistance in Staphylococcus haemolyticus among clinical strains at a tertiary
care hospital in Thailand.
AB - Staphylococcus spp. is a major cause of nosocomial infection and sepsis. However,
increasing drug resistance is becoming a challenge to microbiologists. The
purpose of this study was to identify and determine antimicrobial resistance
phenotypes and drug resistance genes of clinical coagulase-negative staphylococci
(CoNS) isolates at Mae Sot Hospital in Tak province, Thailand. A total of 229
CoNS isolates were collected from clinical specimens during two periods in 2014
and in 2015. Staphylococcus haemolyticus was the most prevalent species (37.55%),
followed by S. epidermidis (21.83%), S. saprophyticus (11.79%) and S. hominis
(11.35%) respectively. The remaining 17.48% of the organisms comprised S.
capitis, S. arlettae, S. cohnii, S. equorum, S. xylosus, S. warneri, S. sciuri,
S. pettenkoferi, S. kloosii and S. lugdunensis. Methicillin-resistant CoNS
(MRCoNS), containing the mecA gene, were detected in 145 of 229 isolates, mostly
found in S. haemolyticus and S. epidermidis. In addition, the differentiation of
their macrolide-lincosamide-streptogramin B (MLSB) resistance phenotypes was
determined by the D-test and corresponding resistance genes. Among 125
erythromycin-resistant CoNS, the prevalence of constitutive type of MLSB,
inducible clindamycin resistance and macrolide-streptogramin B resistance
phenotypes were 72, 13.60 and 14.40% respectively. These phenotypes were
expressed in 80% of MRCoNS strains. In addition, the ermC gene (79.20%) was found
to be more prevalent than the ermA gene (22.40%), especially among MRCoNS. These
results indicate that CoNS may play an important role in spreading of drug
resistance genes. More attention to these organisms in surveillance and
monitoring programs is needed.
PMID- 28702200
TI - Complete genome sequence of the Bifidobacterium animalis subspecies lactis BL3,
preventive probiotics for acute colitis and colon cancer.
AB - We report the genome sequence of Bifidobacterium animalis subspecies lactis BL3,
which has preventive properties on acute colitis and colon cancer. The genome of
BL3, which was isolated from Korean faeces, consisted of a 1 944 323 bp size
single chromosome, and its G+C content was 60.5%. Genome comparison against the
closest Bifidobacterium animalis strain revealed that BL3 had particularly
different regions of four areas encoding flavin-nucleotide-binding protein,
transposase, multidrug ABC transporter and ATP binding protein.
PMID- 28702201
TI - 'Marasmitruncus massiliensis' gen. nov., sp. nov., 'Clostridium culturomicum' sp.
nov., 'Blautia provencensis' sp. nov., 'Bacillus caccae' sp. nov. and
'Ornithinibacillus massiliensis' sp. nov., isolated from stool samples of
undernourished African children.
AB - We report here the main characteristics of five new species, 'Marasmitruncus
massiliensis' strain Marseille-P3646T (CSUR P3646), 'Clostridium culturomicum'
strain Marseille-P3545T (CSUR P3545), 'Blautia provencensis' strain Marseille
P3502T (CSUR P3502), 'Bacillus caccae' strain Marseille-P3604T (CSUR P3604) and
'Ornithinibacillus massiliensis' strain Marseille-P3601T (CSUR P3601), which were
isolated recently from undernourished children's stool samples from Niger using
microbial culturomics.
PMID- 28702202
TI - 'Khoudiadiopia massiliensis' gen. nov., sp. nov., strain Marseille-P2746TT, a new
bacterial genus isolated from the female genital tract.
AB - We report the main characteristics of 'Khoudiadiopia massiliensis' gen. nov., sp.
nov., strain Marseille-P2746T (= CSUR P2746), a new member of the
Peptoniphilaceae family isolated from a vaginal swab of a patient suffering from
bacterial vaginosis.
PMID- 28702203
TI - The effectiveness of naltrexone combined with current smoking cessation
medication to attenuate post smoking cessation weight gain: a literature review.
AB - BACKGROUND: Smoking is the number one cause of preventable morbidity and
mortality globally and although many countries have invested heavily in smoking
cessation programs, 21% of the global population still smoke. Post cessation
weight gain has been identified as a barrier to attempting cessation and is
implicated in the high rates of relapse. Naltrexone has been touted as a possible
solution to address post smoking cessation weight gain. RESULTS: The results from
seven original studies assessing the effectiveness of naltrexone in combination
with existing smoking cessation medications to attenuate post smoking cessation
weight gain were obtained and critically reviewed. Five returned positive results
and two returned results that were statistically insignificant. The positive
results were seen more often in those identified as more likely to exhibit
hedonic eating behaviour for example women and participants who were categorised
as overweight or obese. CONCLUSION: The evidence suggests further investigation
in to a combination of naltrexone and approved smoking cessation medications is
warranted and could provide a solution to attenuate post smoking cessation weight
gain especially in women and those classified as overweight or obese. This may
provide the tool required to remove a perceived barrier to smoking cessation and
improve global statistics.
PMID- 28702204
TI - Exploring the status of retail private drug shops in Bangladesh and action points
for developing an accredited drug shop model: a facility based cross-sectional
study.
AB - BACKGROUND: The private retail drug shops market in Bangladesh is largely
unregulated and unaccountable, giving rise to irrational use of drugs and high
Out-of-pocket expenditure on health. These shops are served by salespersons with
meagre or no formal training in dispensing. METHOD: This facility-based cross
sectional study was undertaken to investigate how the drug shops currently
operate vis-a-vis the regulatory regime including dispensing practices of the
salespersons, for identifying key action points to develop an accredited model
for Bangladesh. About 90 rural and 21 urban retail drug shops from seven
divisions were included in the survey. The salespersons were interviewed for
relevant information, supplemented by qualitative data on perceptions of the
catchment community as well as structured observation of client-provider
interactions from a sub-sample. RESULTS: In 76% of the shops, the owner and the
salesperson was the same person, and >90% of these were located within 30 min
walking distance from a public sector health facility. The licensing process was
perceived to be a cumbersome, lengthy, and costly process. Shop visit by drug
inspectors were brief, wasn't structured, and not problem solving. Only 9% shops
maintained a stock register and 10% a drug sales record. Overall, 65% clients
visited drug shops without a prescription. Forty-nine percent of the salespersons
had no formal training in dispensing and learned the trade through apprenticeship
with fellow drug retailers (42%), relatives (18%), and village doctors (16%) etc.
The catchment population of the drug shops mostly did not bother about dispensing
training, drug shop licensing and buying drugs without prescription. Observed
client-dispenser interactions were found to concentrate mainly on financial
transaction, unless, the client pro-actively sought advice regarding the use of
the drug. CONCLUSIONS: Majority of the drug shops studied are run by salespersons
who have informal 'training' through apprenticeship. Visiting drug shops without
a prescription, and dispensing without counseling unless pro-actively sought by
the client, was very common. The existing process is discouraging for the shop
owners to seek license, and the shop inspection visits are irregular,
unstructured and punitive. These facts should be considered while designing an
accredited model of drug shop for Bangladesh.
PMID- 28702205
TI - Association of arsenobetaine with beta-cell function assessed by homeostasis
model assessment (HOMA) in nondiabetic Koreans: data from the fourth Korea
National Health and Nutrition Examination Survey (KNHANES) 2008-2009.
AB - BACKGROUND: Arsenic is known as an endocrine disruptor that people are exposed to
through various sources such as drinking water and indigestion of marine
products. Although some epidemiological and animal studies have reported a
correlation between arsenic exposure and diabetes development, there are limited
studies regarding the toxic effects of organic arsenic including arsenobetaine on
the human body. Here, we analyzed the association between urine arsenobetaine and
the homeostasis model assessment of beta-cell function (HOMA-beta), which is an
index for predicting diabetes development and reflecting the function of
pancreatic beta-cells. METHODS: In the fourth Korea National Health and Nutrition
Examination Survey (KNHANES), health and nutrition surveys and screening tests
were performed. Of the total survey population, people with confirmed values for
urine total arsenic and arsenobetaine were included, and known diabetic patients
were excluded. A total 369 participants were finally included in the study. We
collected surveys on health, height, body weight, body mass index, blood mercury
level, fasting glucose level, and serum insulin level and calculated HOMA index.
Owing to sexual discrepancy, we performed sexually stratified analysis. RESULTS:
Urine total arsenic and total arsenic minus arsenobetaine was not associated with
HOMA-IR and HOMA-beta in univariate analysis or in sexually stratified analysis.
However, urine arsenobetaine showed a statistically significant relationship with
HOMA-beta in univariate analysis, and only male participants showed a significant
correlation in sexually stratified analysis. In the analysis adjusted for age,
BMI, smoking, alcohol drinking, physical activity and blood mercury, the HOMA
beta value in the group below the 25th percentile of arsenobetaine was
significantly higher than the group between 50 and 75th percentile, while no
difference was shown for HOMA-IR. In sexually stratified analysis, The value of
HOMA-beta was significantly higher in male participants with below the 25th
percentile urine arsenobetaine than the group between 25 and 50th and between 50
and 75th, while no difference was shown for HOMA-IR. However, female participants
did not demonstrate a relationship between HOMA-IR, HOMA-beta and urine
arsenobetaine. CONCLUSION: This study revealed the association between urine
arsenobetaine and pancreatic beta-cell function assessed by HOMA-beta in the
normal population (without diabetes), especially in males, despite adjusting for
factors affecting pancreatic beta-cell function and diabetes.
PMID- 28702206
TI - Gender difference in the impact of gynoid and android fat masses on the
progression of hepatic steatosis in Japanese patients with type 2 diabetes.
AB - BACKGROUND: Increased visceral adiposity is strongly associated with non
alcoholic fatty liver disease (NAFLD). However, little attention has been paid to
the association between the change in subcutaneous adipose mass and the
progression of non-alcoholic fatty liver disease (NAFLD). We aimed to investigate
whether increased subcutaneous adipose tissue (gynoid fat mass) could be
protective against the progression of NAFLD in Japanese patients with type 2
diabetes. METHODS: This is a retrospective observational study of 294 Japanese
patients with type 2 diabetes (65 +/- 10 years old, 40% female). Liver
attenuation index (LAI) measured by abdominal computed tomography was used for
the assessment of hepatic steatosis. Both gynoid (kg) and android (kg) fat masses
were measured by the whole body dual-energy X-ray absorptiometry. One-year
changes in LAI, gynoid, and android fat masses were evaluated in both male and
female patients. Linear regression analysis with a stepwise procedure was used
for the statistical analyses to investigate the association of the changes in
gynoid and android fat masses with the change in LAI. RESULTS: LAI levels at
baseline were 1.15 +/- 0.31 and 1.10 +/- 0.34 in female and male patients (p =
0.455). The change in gynoid fat mass was significantly and positively associated
with the change in LAI in both univariate (standardized beta 0.331, p = 0.049)
and multivariate (standardized beta 0.360, p = 0.016) models in the female
patients. However, no significant association was observed in males. In contrast,
the increase in android fat mass was significantly associated with the reduced
LAI in both genders in the multivariate models (standardized beta -0.651, p <
0.001 in females and standardized beta -0.519, p = 0.042 in males). CONCLUSIONS:
This study provides evidence that increased gynoid fat mass may be protective
against the progression of NAFLD in female Japanese patients with type 2
diabetes.
PMID- 28702207
TI - Alcohol and fertility: how much is too much?
AB - Alcohol use is prevalent in the United States. Given that a substantial portion
of the drinking population is of reproductive age, it is not uncommon for couples
who are attempting conception, or for women who are already pregnant, to be
regularly consuming alcohol. Alcohol use is associated with multiple reproductive
risks, including having a child with a Fetal Alcohol Spectrum Disorder, increased
risk of fetal loss, and decreased chance of live birth. This review serves to
examine the risks of alcohol in the context of reproductive health.
PMID- 28702208
TI - Conjunctival cystectomy assisted by pattern scan laser photocoagulation.
AB - BACKGROUND: To introduce a new technique of laser-assisted conjunctival
cystectomy using pattern scan laser (PASCAL) photocoagulation. CASE PRESENTATION:
A 50-years-old Asian woman presented with a conjunctival cyst in the left eye.
Slit-lamp examination revealed a 5 mm * 2 mm sized freely movable conjunctival
cyst. After a 1 mm * 1 mm sized conjunctival opening was made using PASCAL
photocoagulation, the cyst was extracted using a non-toothed forceps without
rupture. Two weeks later, complete re-epithelialization of the conjunctiva was
observed without any complications. No evidence of recurrence was noted over the
6-month follow-up period. CONCLUSION: Conjunctival cystectomy with the adjunctive
use of PASCAL photocoagulation can be an effective and safe treatment method.
PMID- 28702209
TI - Safety of human papillomavirus vaccines in healthy young women: a meta-analysis
of 24 controlled studies.
AB - BACKGROUND: Human papillomavirus (HPV) vaccines have been shown to be effective
for the eradication of HPV and prevention of cervical cancer. However, the number
of women who receive HPV vaccinations has decreased over the last several years
in Japan, due to concerns about adverse reactions associated with the vaccines.
We evaluated the safety of three types of HPV vaccines separately in young women
and the difference in the risk of adverse reactions between HPV and other
vaccines by conducting a meta-analysis. METHODS: Primary literature was retrieved
from MEDLINE, the Cochrane Central Register of Controlled Trials, and Japana
Centra Revuo Medicina. Prospective controlled studies with participants
consisting exclusively of healthy women who received bivalent, quadrivalent, or 9
valent HPV (2vHPV, 4vHPV or 9vHPV) vaccines were included. Primary safety outcome
was the incidence of solicited local and systemic symptoms, and unsolicited
symptoms. When two or more studies were found for the same analysis, a meta
analysis was applied. RESULTS: A total of 24 controlled studies from 22 articles
were included in our study. Of the 24 studies, 16 were placebo-controlled and
eight were active-controlled (different HPV vaccine or hepatitis vaccine).
Average ages of the participants ranged from 12 to 37 years. A significantly
higher incidence of solicited local symptoms was observed following injection of
HPV vaccines (2vHPV and 4vHPV) compared to placebo, but there was no difference
between HPV vaccines [risk ratio (RR) for 2vHPV: 1.25, 95% confidence interval
(CI): 1.09 to 1.43, RR for 4vHPV: 1.16, 95% CI: 1.11 to 1.20]. The incidence of
solicited systemic symptoms was not different between HPV vaccines and placebo
(RR: 1.04, 95% CI: 0.99 to 1.09). The incidence of unsolicited symptoms was
significantly higher for 2vHPV vaccine compared to placebo (RR: 1.28, 95% CI:
1.01 to 1.63), but was not significantly different between 2vHPV and hepatitis B
vaccines. CONCLUSIONS: HPV vaccines had significantly higher risk of any
injection site symptom compared to placebo or other vaccines (hepatitis A and B
vaccines), and the incidence of solicited local symptoms was no difference
between 2vHPV vaccination and 4vHPV vaccination. However, the most adverse
reactions were transient.
PMID- 28702210
TI - Successful weight loss maintainers use health-tracking smartphone applications
more than a nationally representative sample: comparison of the National Weight
Control Registry to Pew Tracking for Health.
AB - OBJECTIVE: The objective of this paper is to evaluate successful weight loss
maintainers' use of self-monitoring technology. METHODS: National Weight Control
Registry (NWCR) participants, who maintained a >=13.6 kg weight loss for >=1
year, completed an online survey about self-monitoring technology use. The NWCR
sample (n = 794) was compared with a demographically similar subsample of 833
individuals answering the same questions in the Pew Tracking for Health Survey.
RESULTS: The NWCR had higher rates of tracking weight, diet or exercise using any
modality (92.8% vs. 71.3%), on a regular basis (67.4% vs. 41.3%), and frequency
of updating records, compared with Pew (ps < .01). Smartphone ownership was
higher in NWCR participants (80.2% vs. 52.8%, p < .001), and NWCR smartphone
owners had 23.1 times greater odds for using diet, food or calorie counter apps
(58.9% vs. 5.9%) and 15.5 times greater odds for using weight monitoring apps
(31.7% vs. 3.0%; all ps < .01). Pew respondents more often changed their
behaviour based on their tracking data (ps < .01). CONCLUSION: Use of self
monitoring technology is common in weight loss maintainers: more so than in a
nationally representative sample. However, the national sample more often changed
their behaviour based on tracking data, perhaps suggesting that weight loss
maintainers could derive additional benefit from technology they are already
using.
PMID- 28702211
TI - Skipping breakfast and 5-year changes in body mass index and waist circumference
in Japanese men and women.
AB - OBJECTIVE: This study investigated the relationship between frequency of skipping
breakfast and annual changes in body mass index (BMI) and waist circumference
(WC). METHODS: The participants were 4,430 factory employees. BMI and WC were
measured repeatedly at annual medical examinations over a 5-year period. The
association between frequency of skipping breakfast at the baseline examination
and annual changes in anthropometric indices was evaluated using the generalized
estimating equation method. RESULTS: The mean (standard deviation) BMI was 23.3
(3.0) kg m-2 for men and 21.9 (3.6) kg m-2 for women; and the mean WC was 82.6
(8.7) cm for men and 77.8 (9.8) cm for women. During the follow-up period, mean
BMI increased by 0.2 kg m-2 for men and women, and mean WC increased by 1.1 cm
for men and 1.0 cm for women. The annual change in the BMI of men who skipped
breakfast four to six times per week was 0.061 kg m-2 higher, and that of those
who skipped breakfast seven times per week was 0.046 kg m-2 higher, compared with
those who did not skip breakfast. Annual changes in the WC of male participants
who skipped breakfast seven times per week was 0.248 cm higher than that of those
who did not skip breakfast. Skipping breakfast was not associated with changes in
BMI or WC in women. CONCLUSIONS: Skipping breakfast was closely associated with
annual changes in BMI and WC among men, and eating breakfast more than four times
per week may prevent the excessive body weight gain associated with skipping
breakfast.
PMID- 28702212
TI - Obesity, arterial function and arterial structure - a systematic review and meta
analysis.
AB - OBJECTIVE: Obesity is an established risk factor for cardiovascular disease. The
mechanisms by which obesity affects cardiovascular risk have not been fully
elucidated. This paper reports a comprehensive systematic review and meta
analysis on obesity and two key aspects of vascular health using gold-standard
non-invasive measures - arterial endothelial function (brachial flow-mediated
dilatation) and subclinical atherosclerosis (carotid intima-media thickness).
METHODS: Electronic searches for 'Obesity and flow-mediated dilatation' and
'Obesity and intima-media thickness' were performed using Ovid Medline and Embase
databases. A meta-analysis was undertaken for brachial flow-mediated dilatation
and carotid intima-media thickness to obtain pooled estimates for adults with
obesity and those with healthy weight. RESULTS: Of the 5,810 articles retrieved,
19 studies on flow-mediated dilatation and 19 studies on intima-media thickness
were included. Meta-analysis demonstrated that obesity was associated with lower
flow-mediated dilatation (-1.92 % [95% CI -2.92, -0.92], P = 0.0002) and greater
carotid intima-media thickness (0.07 mm [95% CI 0.05, 0.08], P < 0.0001).
CONCLUSIONS: Obesity is associated with poorer arterial endothelial function and
increased subclinical atherosclerosis, consistent with these aspects of vascular
health at least partially contributing to the increased risk of cardiovascular
events in adults with obesity. These estimated effect sizes will enable vascular
health benefits in response to weight loss treatment to be put in greater
perspective, both in the research setting and potentially also clinical practice.
PMID- 28702213
TI - Monitoring the efficacy of omega-3 supplementation on liver steatosis and carotid
intima-media thickness: a pilot study.
AB - PURPOSE: To determine the effects of omega-3 supplementation on liver fat and
carotid intima-media thickness (IMT) and to assess accuracy of ultrasound (US)
for grading liver steatosis. MATERIALS AND METHODS: In this one-way crossover
pilot study, we assigned children with obesity and liver steatosis to receive 1.2
g daily of omega-3 supplementation vs. inactive sunflower oil for 24 or 12 weeks.
Liver fat content was assessed by magnetic resonance spectroscopy (MRS), magnetic
resonance imaging (MRI) and US, and common carotid IMT by US. Statistical
analysis included Chi-square, Student's t-tests, ANOVA tests and receiver
operating characteristic (ROC) curves. RESULTS: Omega-3 supplementation was
associated with a trend towards decrease in MRS-determined liver fat fraction
(0.7% and 2.1% decrease in the 24-week and 12-week omega-3 group, respectively)
compared with the sunflower oil group (1.0% increase). These changes were not
significant, whether assessed by MRS (P = 0.508), MRI (P = 0.508) or US (P =
0.678). Using US, the area under the ROC curves were 0.964, 0.817 and 0.783 for
distinguishing inferred steatosis grades 0 vs. 1-2-3, 0-1 vs. 2-3 and 0-1-2 vs.
3, respectively, indicating good accuracy of US-based fat grading. Omega-3
supplementation was associated with a decrease in US-determined IMT (0.05-mm
decrease in the 24-week omega-3 group. A 0.015-mm increase was found in the 12
week omega-3 group, and a 0.007-mm decrease in the sunflower oil group (P =
0.003). CONCLUSION: Omega-3 supplementation had no significant effect on liver
fat fraction, but led to carotid IMT decrease in children with obesity and liver
steatosis.
PMID- 28702214
TI - Involvement of oxidative stress in atherosclerosis development in subjects with
sarcopenic obesity.
PMID- 28702215
TI - Relationship between sudden natural death and abdominal fat evaluated on
postmortem CT scans.
AB - OBJECTIVE: This study examined the association between sudden natural death and
abdominal fat using postmortem computed tomography (CT) scans. SUBJECTS AND
METHODS: Postmortem CT images at the umbilical level of 241 subjects were used to
measure abdominal areas of subcutaneous- and visceral fat, the rate of visceral
fat and the waist circumference. Of the study subjects, 174 died of sudden
natural death (130 men and 44 women), and 67 died of different causes (46 men and
21 women). All were between 40 and 75 years of age. Logistic regression analysis
was performed to identify independent abdominal parameters associated with sudden
natural death. RESULTS: By univariate analysis, the areas of subcutaneous and
visceral fat were significantly larger in sudden natural death than who died of
different causes (subcutaneous fat, odds ratio [OR] = 1.004, 95% confidence
interval [CI] = 1.000-1.007, p = 0.03; visceral fat, OR = 1.008, 95% CI = 1.003
1.013, p < 0.01). Multivariate analysis showed that the area of visceral fat was
an independent factor associated with the risk of sudden natural death (OR =
1.008, 95% CI = 1.002-1.015, p = 0.02). CONCLUSIONS: Postmortem CT revealed that
sudden natural death was related to abdominal fat deposits.
PMID- 28702216
TI - Hidden biofilms in a far northern lake and implications for the changing Arctic.
AB - Shallow lakes are common across the Arctic landscape and their ecosystem
productivity is often dominated by benthic, cyanobacterial biofilms. Many of
these water bodies freeze to the bottom and are biologically inactive during
winter, but full freeze-up is becoming less common with Arctic warming. Here we
analyzed the microbiome structure of newly discovered biofilms at the deepest
site of a perennially ice-covered High Arctic lake as a model of polar microbial
communities that remain unfrozen throughout the year. Biofilms were also sampled
from the lake's shallow moat region that melts out and refreezes to the bottom
annually. Using high throughput small subunit ribosomal RNA sequencing, we found
more taxonomic richness in Bacteria, Archaea and microbial eukaryotes in the
perennially unfrozen biofilms compared to moat communities. The deep communities
contained both aerobic and anaerobic taxa including denitrifiers, sulfate
reducers, and methanogenic Archaea. The water overlying the deep biofilms was
well oxygenated in mid-summer but almost devoid of oxygen in spring, indicating
anoxia during winter. Seasonally alternating oxic-anoxic regimes may become
increasingly widespread in polar biofilms as fewer lakes and ponds freeze to the
bottom, favoring prolonged anaerobic metabolism and greenhouse gas production
during winter darkness.
PMID- 28702217
TI - Erratum to: Culturally adaptive storytelling intervention versus didactic
intervention to improve hypertension control in Vietnam: a cluster randomized
controlled feasibility trial.
AB - [This corrects the article DOI: 10.1186/s40814-017-0136-9.].
PMID- 28702218
TI - Effects of a parallel-arm randomized controlled weight loss pilot study on
biological and psychosocial parameters of overweight and obese breast cancer
survivors.
AB - BACKGROUND: Weight gain often occurs after breast cancer (BC) diagnosis and
obesity along with sedentary behavior are associated with increased risk of BC
recurrence and mortality. The primary objective of this study was to determine
whether a significant weight loss, of approximately 10%, would lead to beneficial
changes in biomarkers associated with cancer and/or cancer recurrence, and
quality of life (QOL) in overweight and obese BC survivors. METHODS: This
parallel-arm study took place in Minneapolis, Minnesota, from January 2009 until
March 2010. Participants were overweight and obese postmenopausal BC survivors
who had completed treatment at least 3 months prior to enrollment and who did not
smoke. Twenty-one BC survivors were randomized, via a random number generator
computer software, to a 1000-calorie deficit feeding and exercise intervention
(CR) or a weight management counseling intervention (WM) for 12 weeks followed by
a 6-week follow-up. Body weight, biomarkers, and QOL were measured at baseline,
weeks 6, 12, and 18. Body composition and fitness level were measured at only two
time points. RESULTS: Twenty-one women were enrolled into the study and 20
completed all time points. Weight loss occurred with both interventions. Body
weight in CR changed from 85.5 (95% confidence interval (CI) 77, 94) kg to 76.7
(95% CI 68.1, 85.2) kg, whereas in WM it changed from 98.3 (95% CI 89.8, 106.8)
kg to 93.2 (95% CI 84.6, 101.7) kg. Fitness in CR changed from 4.9 (95% CI 4,
5.8) to 6.3 (95% CI 5.4, 7.2). CR led to lower plasma levels of leptin, F2
isoprostanes, and CRP. Quality of life seemed to improve with both interventions,
while sleep quality decreased only in CR. CONCLUSIONS: Overweight and obese BC
survivors were able to adhere to a strict diet and exercise program, which
significantly decreased body weight, increased fitness level, and improved
biomarkers and QOL. However, the strict dietary intervention in CR seemed to
decrease participants' sleep quality and social relationships. Future larger
randomized controlled trials should focus on behavioral modification and
personalized nutrition counseling to help breast cancer survivors achieve a
sustainable weight loss and fitness level. TRIAL REGISTRATION: ClinicalTrials.gov
identifier: NCT02940470.
PMID- 28702219
TI - Modification and optimization of electrospun gelatin sheets by electron beam
irradiation for soft tissue engineering.
AB - BACKGROUND: Crosslinked gelatin nanofibers are one of the widely used scaffolds
for soft tissue engineering. However, modifying the biodegradation rate of
chemically crosslinked gelatin is necessary to facilitate cell migration and
tissue regeneration. Here, we investigated the optimal electron beam (e-beam)
irradiation doses with biodegradation behavior on changes in the molecular
weight, morphology, pore structure, and cell proliferation profiles of
electrospun nanofibrous gelatin sheets. METHODS: The molecular weights of
uncrosslinked gelatin nanofibers were measured using gel permeation
chromatography. The morphology and pore structure of the gelatin scaffolds were
analyzed by scanning electron microscopy and a porosimeter. Biodegradation tests
were performed in phosphate-buffered saline solutions for 4 weeks. Cell
proliferation and tissue regeneration profiles were examined in fibroblasts using
WST-1 assays and hematoxylin and eosin staining. RESULTS: Crosslinked gelatin
nanofiber sheets exposed to e-beam irradiation over 300 kGy showed approximately
50% weight loss in 2 weeks. Gelatin scaffolds exposed to e-beam irradiation at
100-200 kGy showed significantly increased cell proliferation after 7 days of
incubation. CONCLUSIONS: These findings suggested that the biodegradation and
cell proliferation rates of gelatin nanofiber scaffolds could be optimized by
varying e-beam irradiation doses for soft tissue engineering.
PMID- 28702220
TI - Better care for people with diabetes and endocrine diseases.
PMID- 28702221
TI - Management of diabetes mellitus in patients with chronic kidney disease.
AB - Glycemic control is essential to delay or prevent the onset of diabetic kidney
disease. There are a number of glucose-lowering medications available but only a
fraction of them can be used safely in chronic kidney disease and many of them
need an adjustment in dosing. The ideal target hemoglobin A1c is approximately 7
% but this target is adjusted based on the needs of the patient. Diabetes control
should be optimized for each individual patient, with measures to reduce diabetes
related complications and minimize adverse events. Overall care of diabetes
necessitates attention to multiple aspects, including reducing the risk of
cardiovascular disease, and often, multidisciplinary care is needed.
PMID- 28702222
TI - RETRACTED ARTICLE: Fatal factitious Cushing syndrome (Munchhausen's syndrome) in
a patient with macroprolactinoma and silent corticotrophinoma: case report and
literature review.
AB - Munchhausen's syndrome (MS) is a chronic factitious disorder characterized by the
intentional production of clinical symptoms without external incentive. One type
of MS is factitious Cushing syndrome, an extremely rare clinical situation in
which the diagnosis is challenging mainly due to interference of the exogenous
medication in cortisol immunoassays. We described a 26-year-old woman who was
originally diagnosed with a macroprolactinoma and during follow-up developed
clinical and laboratorial hypercortisolism. A transsphenoidal surgery was
performed and immunohistochemistry revealed positive and diffuse staining for
both hormones. Four years later, her hypercortisolism recurred and the
confirmation of factitious Cushing syndrome was delayed due to conflicting
laboratorial results. There are few cases in the literature of factitious Cushing
syndrome, and only one had a fatal outcome. The diagnosis of this condition is
complex and includes cyclic Cushing syndrome in the differential diagnosis. These
patients have high morbidity and increased mortality risk and are likely to have
other psychiatric disorders. Prednisone was identified as the culprit in the
majority of the cases.
PMID- 28702223
TI - The potential role of incretin therapy in the hospital setting.
AB - Hyperglycemia has been associated with increased morbidity and mortality in
hospitalized patients. Insulin has traditionally been the drug of choice for
managing hyperglycemia in this setting, but carries a significant risk of
hypoglycemia. Incretin-based therapies, including glucagon-like peptide-1,
glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors,
have potential use in the hospital. These agents have a relatively low risk of
hypoglycemia, favorable short-term side effect profile, and can be used alone or
in combination with insulin. Several small studies have supported the safety and
efficacy of incretin therapies in the inpatient setting with the majority of data
coming from the intensive care setting. Large-scale clinical studies are needed
to further evaluate the potential role of incretins in the management of
inpatient hyperglycemia.
PMID- 28702224
TI - Management of macroprolactinomas.
AB - Prolactin (PRL) secreting tumors are the most common functional neoplasms of the
pituitary and are commonly subdivided into microprolactinomas (<10 mm) and
macroprolactinomas (>=10 mm) according to their baseline diameter. Patients with
prolactinoma present with symptoms evolving from hyperprolactinemia and with
those caused by pressure of the expanding mass on surrounding tissues, including
the optic chiasm and the cavernous sinuses. We hereby describe the possible
complications of macroprolactinomas, including mass effects, hypopituitarism, CSF
leak and apoplexy and discuss their relevant management. In general, all patients
harboring macroprolactinomas should be treated, the objectives being to achieve
normal or near normal PRL levels, to reduce or stabilize adenoma size and to
recover altered pituitary axes. Medical therapy with dopamine agonists (DA) is
the preferred initial treatment for the vast majority of patients harboring
prolactinomas. Pituitary surgery is indicated in patients who cannot tolerate or
are resistant to therapy with DAs, patients that seek fertility and harbor
adenomas that impinge on the optic chiasm, psychiatric patients with
contraindication to DA treatment and patients presenting with pituitary apoplexy
or a cerebrospinal fluid (CSF) leak. In addition, in this review, several patient
populations with unique clinical characteristics will be discussed separately
namely postmenopausal women, the elderly, children and patients with pituitary
carcinoma.
PMID- 28702225
TI - The association of dyslipidemia and obesity with glycated hemoglobin.
AB - BACKGROUND: Dyslipidemia and obesity are the most common complex metabolic
disorders taking the highest toll of health resources globally by its increasing
incidences. This consequently leads to type 2 diabetes mellitus (T2DM) and
cardiovascular disorders (CVDs) with variable reports about the role of metabolic
factors on glycemic control. The current study is designed to determine the
association of dyslipidemia and obesity with glycated hemoglobin (HbA1c) in T2DM
and non-diabetic subjects. METHODS: The present study was carried out in 931
subjects from urban Western India including 430 diabetic and 501 non-diabetic
subjects with detailed anthropometric parameters. All subjects were investigated
for HbA1c and lipid parameters like TC, TG, HDL-C, LDL-C and non-HDL-C. RESULTS:
Dyslipidemia, central- and peripheral- obesity were observed (50.27 %; 75 % and
59.83 %) in all the study subjects respectively. Additionally, hyper-non-HDL-C
was detected in 23.49 % and 22.56 % in T2DM and non-diabetic subjects.
Significant linear associations of hyper-TC, hyper-LDL-C and hyper-non-HDL-C were
observed with HbA1c in T2DM and non-diabetic control subjects respectively.
Centrally- and peripherally- obese dyslipidemic subjects also showed a
significant association with HbA1c in T2DM and control subjects respectively.
CONCLUSION: This study demonstrates the high prevalence of dyslipidemia and
obesity in all subjects irrespective of their disease status in a Western Indian
population. The dyslipidemic obese subjects had significant linear association
with HbA1c in T2DM subjects.
PMID- 28702226
TI - Relationship between oxidative stress and haematological indices in patients with
diabetes in the Ghanaian population.
AB - BACKGROUND: Persistent hyperglycaemia is a hallmark of Diabetes Mellitus (DM). It
causes increased production of free radicals, especially reactive oxygen species
(ROS), - resulting in oxidative stress. Reactive Oxygen Species have been
implicated in the development of haematological complications in patients with
diabetes. Superoxide Dismutase (SOD) is one of the most effective antioxidant
enzyme defense systems against free radicals. METHODS: From February through May
2014, we assessed the relationship between oxidative stress and haematological
profiles among individuals with and without diabetes. A cross sectional study of
66 case patients and 44 age-matched controls were recruited from the National
Diabetes Management and Research Centre (NDMRC), Korle-Bu Teaching Hospital,
Accra, Ghana. Blood samples were obtained from study participants with consent.
We determined the haematological profiles of study participants and measured
their oxidative stress levels using a standardized kit for SOD activity. RESULTS:
Higher white blood cell (WBC) counts were seen in the diabetes cohort (p-value =
0.023). The SOD activity tended to be lower in diabetes patients (p-value = 0.144
however) while higher neutrophil levels seemed to correlate with SOD activity (R
= 0.249; R2 = 6.2 %; p-value = 0.049). There did not appear to be a correlation
between fasting blood glucose (FBG) and SOD activity (R = -0.044; p-value =
0.727). CONCLUSION: The study reports similar oxidative stress levels, as
measured by SOD activity, in diabetic and non-diabetic adults. The SOD activity
did not appear to correlate with FBG and several other haematological parameters.
Further study would be required to investigate the relationship between these
haematological indices and diabetic micro- and macro-vascular complications in
our population.
PMID- 28702227
TI - Driving and diabetes: problems, licensing restrictions and recommendations for
safe driving.
AB - Driving is a complex process that places considerable demands on cognitive and
physical functions. Many complications of diabetes can potentially impair driving
performance, including those affecting vision, cognition and peripheral neural
function. Hypoglycemia is a common side-effect of insulin and sulfonylurea
therapy, impairing many cognitive domains necessary for safe driving performance.
Driving simulator studies have demonstrated how driving performance deteriorates
during hypoglycemia. Driving behavior that may predispose to hypoglycemia while
driving is examined. Studies examining the risk of road traffic accidents in
people with insulin-treated diabetes have produced conflicting results, but the
potential risk of hypoglycemia-related road traffic accidents has led to many
countries imposing restrictions on the type and duration of driving licenses that
can be issued to drivers with diabetes. Guidance that promotes safe driving
practice has been provided for drivers with insulin-treated diabetes, which is
the group principally addressed in this review.
PMID- 28702228
TI - The cost-effectiveness of diabetes prevention: results from the Diabetes
Prevention Program and the Diabetes Prevention Program Outcomes Study.
AB - BACKGROUND: The Diabetes Prevention Program (DPP) was a randomized, controlled
clinical trial. It demonstrated that among high-risk individuals with impaired
glucose tolerance, diabetes incidence was reduced by 58 % with lifestyle
intervention and 31 % with metformin compared to placebo. During the Diabetes
Prevention Program Outcomes Study (DPPOS), all DPP participants were unmasked to
their treatment assignments, the original lifestyle intervention group was
offered additional lifestyle support, the metformin group continued metformin,
and all three groups were offered a group-implemented lifestyle intervention.
Over the 10 years of combined DPP/DPPOS follow-up, diabetes incidence was reduced
by 34 % in the lifestyle group and 18 % in the metformin group compared to
placebo. The purpose of this article is to review and synthesize analyses
published by the DPP/DPPOS Research Group that have described the cost
effectiveness of diabetes prevention. METHODS: We describe the resource
utilization and costs of the DPP and DPPOS interventions, the costs of non
intervention-related medical care, the impact of the interventions on diabetes
progression and quality-of-life, and the cost-effectiveness of the interventions
from health system and societal perspectives. Cost-effectiveness analyses were
performed with a 3-year time horizon using DPP data, a lifetime time horizon that
simulated 3-year DPP data, and a 10-year time horizon using combined DPP/DPPOS
data. RESULTS: Although more expensive than the placebo intervention, the greater
costs of the lifestyle and metformin interventions were offset by reductions in
the costs of nonintervention-related medical care. Every year after
randomization, quality-of-life was better for participants in the lifestyle
intervention compared to those in the metformin or placebo intervention. In both
the simulated lifetime analysis and the 10-year within trial economic analysis,
lifestyle and metformin were extremely cost-effective (that is, improved outcomes
at a low incremental cost) or even cost-saving (that is, improved outcomes and
reduced total costs) compared to the placebo intervention. CONCLUSIONS: The
implementation of diabetes prevention programs in high-risk individuals will
result in important health benefits and represents a good value for money. TRIAL
REGISTRATION: NCT00004992 (DPP) and NCT00038727 (DPPOS).
PMID- 28702229
TI - Detemir plus aspart and glulisine induced lipoatrophy: 2015 literature review and
report of a new case.
AB - BACKGROUND: In the first and only literature review, conducted in 2009, of human
insulin analog- induced lipoatrophy, there were 12 published cases, including 1
with aspart, 1 with detemir, 1 with NovoMix 30 and none with detemir plus aspart.
It is perceived that insulin analog induced-lipoatrophy is increasing. We
conducted a 2015 literature review of published reports of lipoatrophy induced by
aspart, detemir, detemir plus aspart, and NovoMix30. We also report a new case of
detemir plus aspart and glulisine induced lipoatrophy. METHODS: Our focused
literature searches (limited to 1995-2014) in PubMed, Embase, and Web of Science,
using a combination of insulin analog and lipoatrophy terminology, was conducted
in early January 2015. RESULTS: From the 520 unique citations there were 33 (from
13 papers and 9 abstracts) lipoatrophy cases induced by detemir (n = 5), aspart
(n = 21), detemir plus aspart (n = 4) and NovoMix 30 (n = 3), representing 30 new
cases since 2009. Many of these reported cases were females (76 %), had type 1
diabetes mellitus (T1DM) (94 %) and were in young persons (61 %). A 41-year-old
T1DM woman developed lipoatrophy on her upper thighs, arms and abdomen 14 months
after injecting detemir plus aspart at the same sites. Later on, after a year on
continuous subcutaneous insulin infusion (CSII) using aspart and then glulisine,
she developed lipoatrophy at the infusion sites. When CSII insulin was switched
to lispro she did not develop lipoatrophy after 10 months. Meanwhile, the
original lipoatrophy sites significantly improved. CONCLUSIONS: Our literature
review uncovered 30 new published cases of aspart, detemir, aspart plus detemir
and NovoMix 30-induced lipoatrophy since 2009. The largest increase in cases was
in aspart- induced lipoatrophy. Recent surveys showed most rapid acting insulin
analog-induced lipoatrophy were associated with CSII. In our review of the
reported cases, 85.7 % cases of aspart-induced lipoatrophy were associated with
CSII. As in previous reports, we showed lipoatrophy was more common in females,
T1DM and young persons. Our patient may be the 5th published case of detemir plus
aspart-induced lipoatrophy and possibly the first case report of glulisine
induced lipoatrophy. She believed both detemir plus aspart and glulisine induced
the lipoatrophy.
PMID- 28702230
TI - RETRACTED ARTICLE: Thyroid nodules update in diagnosis and management.
AB - Thyroid nodules are very common. With widespread use of sensitive imaging in
clinical practice, incidental thyroid nodules are being discovered with
increasing frequency. Their clinical importance is primarily related to the need
to exclude malignancy (4.0 to 6.5 percent of all thyroid nodules), assess for
their functional status and any pressure symptoms caused by them. New Molecular
tests are marketed for the assessment of thyroid nodules for the presence of
cancer. The high prevalence of thyroid nodules requires evidence-based rational
strategies for their differential diagnosis, risk stratification, treatment, and
follow-up. This review addresses advances and controversies in thyroid nodule
evaluation, including the new molecular tests, and their management considering
the current guidelines and supporting evidence.
PMID- 28702231
TI - Metabolic effects of Foofoo corn on healthy volunteers: influence of some
traditional Cameroonian sauces.
AB - BACKGROUND: Little data to guide diet prescription exists about the foods most
frequently consumed in Africa. Moreover, the sauce accompanying a meal can
significantly alter the metabolic effects of food. Our work was to study the
influence of sauces on the metabolic effects of foofoo corn (Zea mays), one of
the most commonly consumed foods in several countries in sub-Saharan Africa with
a wide range of sauces. METHODS: Our study population consisted of ten healthy
volunteers (five men, five women), aged from 21 to 28 years, with mean BMI of
23.9 (SD 1.9) kg/m2. The study involved seven visits of three hours each,
conducted every 2 days, including one devoted to the oral glucose tolerance test
(OGTT) and six visits to the consumption of each of 6 meals tested, standardized
to 75 g of carbohydrate intake. Blood samples were collected at 0, 15, 30, 60,
90, 120 and 180 min after consumption of meals for blood glucose and
triglycerides levels. The glucose area under the curve of each tested meal, was
used to calculate its glycemic index, using the OGTT as the reference. The
accompanying sauces tested with foofoo corn were: okra sauce (Abelmoschus
esculentus), the so-called yellow sauce (Elaeis guinensis), the pistachio sauce
(Pistacia vera), the nkui (Triumpheta pentandra), ndole (Vernonia amygdalima) and
cabbage (Brassica oleracea). RESULTS: All meals had generally a low glycemic
index, with a maximum of 22.59 % for okra and cabbage, followed by ndole (20.18
%), the yellow sauce (13.10 %), pistachio sauce (11.60 %), and nkui (5.27 %).
There was a difference in the effects of the diets on triglyceride levels only at
180 min (p = 0.03). CONCLUSION: Whatever the accompanying sauce, foofoo corn has
a low glycemic index. Some sauces, such as nkui give it a very low glycemic index
and may be of great interest in diet prescription for patients with various
metabolic disorders such as diabetes and obesity.
PMID- 28702232
TI - Clinical case seminar: unraveling the mystery of abnormal thyroid function tests.
AB - A 53 year old woman was referred to us because of large goiter, enlarged
pituitary and grossly elevated TSH and free T4. The differential diagnosis
included a TSH producing adenoma vs. artifactual laboratory tests. A careful step
by step analysis of different possibilities allowed correct diagnosis and
treatment.
PMID- 28702233
TI - Determinants of nurse satisfaction using insulin pen devices with safety needles:
an exploratory factor analysis.
AB - BACKGROUND: A paucity of data exists to examine nurses' satisfaction with the use
of insulin pens with safety needles in hospitalized patients with diabetes. We
investigated major determinants of nurses' preference of the method of insulin
administration in the context of a General Hospital in Northern Italy. METHODS:
Consecutive patients admitted to three hospital units of different care intensity
requiring insulin received insulin therapy through either the vial/syringe method
(October to December 2012) or pen/safety needles with dual-ended protection
method (January to March 2013). Before the implementation of insulin pens, floor
nurses received a specific training program for proper insulin pen injection
technique including individual testing of the devices (pen/safety needles). At
the end of the study, nurses completed the Nursing Satisfaction Survey
Questionnaire. Cronbach's alpha was used to determine the internal consistency
and reliability of the questionnaire. Major determinants of satisfaction were
investigated through an exploratory factor analysis. The association between each
retained factor and time spent to teach patients how to self-inject insulin with
pen devices was also investigated. RESULTS: Fifty-three out of 60 nurses (mean
age +/- SD 36.2 +/- 8.5 years, 85 % women, 57 % with 10+ years of working
experience) returned the questionnaire. Internal consistency of the questionnaire
was satisfactory (Cronbach's alpha > 0.9). Three months after their introduction,
about 92 % of nurses considered pen devices an "improvement" over the
vial/syringe method. Two factors explained 85 % of nurses' satisfaction, one
related to convenience and ease of use, and the other to satisfaction/time spent
for dose preparation and administration. The latter factor was inversely
correlated with time spent on patients' training tasks. CONCLUSIONS: Nurses'
satisfaction with pen devices was higher than previously reported, possibly
reinforced by safety needles with dual-ended protection. Perceived workload was a
major determinant of nurse satisfaction using pen devices with safety needles. To
facilitate the introduction of insulin pens in the hospital setting, it should be
specifically addressed during training programs in the switch-over period.
PMID- 28702234
TI - Managing diabetes in the digital age.
AB - The prevalence of diabetes is rising globally. Poor glucose control results in
higher rates of diabetes-related complications and an increase in health care
expenditure. Diabetes self-management education (DSME) training has shown to
improve glucose control, and thus may reduce long-term complications.
Implementation of diabetes self-management education programs may not be feasible
for all the institutions or in developing countries due to lack of resources and
higher costs associated with DSME training. With the increasing use of
smartphones and Internet, there is an opportunity to use digital tools for
training people with diabetes to self-manage their disease. A number of mobile
applications, Internet portal, and websites are available to help patients to
improve their diabetes care. However, the studies are limited to show its
effectiveness and cost-benefits in diabetes self-management. In addition, there
are many challenges ahead for the digital health industry. In this review, we
assess the use of newer technologies and digital health in diabetes self
management with a focus on future directions and potential challenges.
PMID- 28702235
TI - Total costs of basal or premixed insulin treatment in 5077 insulin-naive type 2
diabetes patients: register-based observational study in clinical practice.
AB - BACKGROUND: To investigate the costs of treatment with basal insulin (insulin NPH
[NPH], insulin glargine [IG], insulin determir [IG]), and premixed insulin (PM)
in routine clinical care. METHODS: Cohort study based on data from the Swedish
National Diabetes Register, including 5077 insulin-naive men and women with type
2 diabetes, resident in a distinct geographical region of Sweden. Patients were
included between 1 July 2006 and 31 December 2009 and followed for 12 months. All
drug- and healthcare-related costs, stratified by diabetes-related or non
diabetes care contacts, were quantified and compared to baseline. RESULTS:
Initiation of insulin treatment generally entails increased diabetes-related
health care contacts and treatment costs, and decrease in health care costs. The
median changes in costs were generally smaller than the mean changes, reflecting
great variations between patients. The treatment costs were higher for IG, ID and
PM compared with NPH, although higher age, history cardiovascular disease and
diabetes complications as well as higher diabetes-related and other treatment
costs were independent predictors. Overall, only PM (but not IG or ID) were
associated with higher diabetes-related health care costs, although these were
also independently predicted by cardiovascular morbidity and markers of
complicated diabetes. CONCLUSIONS: This study demonstrates that the initiation of
insulin in patients with type 2 diabetes in clinical practice leads to increased
health care contacts, overall and treatment costs, but also generally results in
a decrease in health care costs. The diabetes-related treatment cost was lowest
using NPH insulin but only premixed insulin was associated with higher diabetes
related health care costs than NPH.
PMID- 28702236
TI - Charcot stage 0: A review and consideratons for making the correct diagnosis
early.
AB - Charcot neuropathic osteoarthropathy (CN) is a rare disease (NIDDK, NIH Summary
Report Charcot Workshop, 2008) that causes significant morbidity and mortality
for affected patients. The disease can result in severe deformities of the foot
and ankle that contribute to the development of ulcerations and amputations.
Medical advances have failed to find ways to stop the progression of the disease.
However, it is known that early detection of the CN has a substantial impact on
patient outcomes. CN in the earliest stage is very difficult to recognize and
differentiate from other similar presenting diseases. We intend to outline
clinical considerations practitioners can use when evaluating a patient with
early stage suspected CN.
PMID- 28702237
TI - The Nurse Education and Transition (NEAT) model: educating the hospitalized
patient with diabetes.
AB - BACKGROUND: The number of patients with a diabetes mellitus (DM)-related
diagnosis is increasing, yet the number of hospital-based diabetes educators is
being reduced. Interest in determining effective ways for staff nurses to deliver
diabetes education (DE) is mounting. The purpose of this multi-phase feasibility
study was to develop and evaluate the Nurse Education and Transition (NEAT)
inpatient DM education model. METHODS: Exploratory focus groups were conducted
with staff nurses from inpatient units at academic tertiary and community
hospitals to gain insight into barriers, content, delivery and support mechanisms
related to providing DE to hospitalized patients. Findings informed the
development of the NEAT model, which included a delivery protocol and toolkit
with brief educational videos on key diabetes topics uploaded onto iPads, patient
assessments and "teach back" tools, a discharge survival skills summary sheet,
and guidelines for electronic medical record documentation and scheduling
outpatient DE visits. Trained staff nurses used NEAT to deliver DE to
hospitalized patients with DM and then participated in follow-up focus groups to
assess their experiences, with particular attention to the usefulness of NEAT in
meeting the needs of nurses related to the delivery of diabetes survival skill
education. Information generated was analyzed to identify emerging key themes.
RESULTS: Exploratory focus groups revealed that staff nurses view teaching
patients with DM as part of their job, but report barriers. Nurses agreed that
inpatient DE should be designed to assure safety after discharge and advised that
it be patient-centered, targeted, assessment-based and user friendly. Nurses who
participated in the delivery of NEAT found that the process and tools met the
majority of the basic DE needs of their patients while relieving their workload.
In particular, they reported that video and iPad technology provided a convenient
and standardized method for facilitating teaching at the bedside, but requested
that an interactive feedback mechanism be added to encourage patient self
knowledge assessment. CONCLUSIONS: This study presents challenges staff nurses
face in providing DE to hospitalized patients and identifies opportunities and
strategies for improving content and delivery to ensure safe transition of
patients with DM from hospital to outpatient setting.
PMID- 28702238
TI - Tacrolimus toxicity in islet transplantation due to interaction with macrolides.
AB - BACKGROUND: Drug interactions are an important risk in transplant patients. Case
presentation: This case describes an incident where a patient with islet
transplantation, who was using tacrolimus as part of the immunosuppressant
regime, was started on a course of clarithromycin and experienced nephrotoxicity
and neurotoxicity. He was an outpatient at that time and was managed with
temporary cessation of tacrolimus until the tacrolimus level returned to target
and his symptoms resolved. He recovered well and was resumed on his usual dosage
of tacrolimus to prevent rejection of islets. CONCLUSION: Care should be taken
with commonly used antibiotics to avoid potentially dangerous interactions with
immunosuppressant drugs.
PMID- 28702239
TI - Thyroid dysfunction in metabolic syndrome patients and its relationship with
components of metabolic syndrome.
AB - BACKGROUND: A growing body of evidence suggests that metabolic syndrome is
associated with endocrine disorders including thyroid dysfunction. Thyroid
dysfunction in metabolic syndrome patients may further add to cardiovascular
disease risk thereby increasing mortality. This study was done to assess thyroid
function in metabolic syndrome patients and evaluate its relationship with the
components of metabolic syndrome. METHODS: A cross sectional study was carried
out among 169 metabolic syndrome patients at B P Koirala Institute of Health
Sciences, Dharan, Nepal. Anthropometric measurements (height, weight, waist
circumference) and blood pressure were taken. Fasting blood samples were analysed
to measure glucose, triglyceride, high density lipoprotein (HDL) cholesterol and
thyroid hormones (triiodothyronine, thyroxine and thyroid stimulating hormone).
RESULTS: Thyroid dysfunction was seen in 31.9 % (n = 54) metabolic syndrome
patients. Subclinical hypothyroidism (26.6 %) was the major thyroid dysfunction
followed by overt hypothyroidism (3.5 %) and subclinical hyperthyroidism (1.7 %).
Thyroid dysfunction was much common in females (39.7 %, n = 29) than males (26 %,
n = 25) but not statistically significant (p = 0.068). The relative risk of
having thyroid dysfunction in females was 1.525 (CI: 0.983-2.368) as compared to
males. Significant differences (p = 0.001) were observed in waist circumference
between patients with and without thyroid dysfunction and HDL cholesterol which
had significant negative correlation with thyroid stimulating hormone.
CONCLUSIONS: Thyroid dysfunction, particularly subclinical hypothyroidism is
common among metabolic syndrome patients, and is associated with some components
of metabolic syndrome (waist circumference and HDL cholesterol).
PMID- 28702240
TI - Brief review: cell replacement therapies to treat type 1 diabetes mellitus.
AB - Human embryonic stem cells (hESCs) and induced pluripotent cells (iPSCs) have the
potential to differentiate into any somatic cell, making them ideal candidates
for cell replacement therapies to treat a number of human diseases and regenerate
damaged or non-functional tissues and organs. Key to the promise of regenerative
medicine is developing standardized protocols that can safely be applied in
patients. Progress towards this goal has occurred in a number of fields,
including type 1 diabetes mellitus (T1D). During the past 10 years, significant
technological advances in hESC/iPSC biochemistry have provided a roadmap to
generate sufficient quantities of glucose-responsive, insulin-producing cells
capable of eliminating diabetes in rodents. Although many of the molecular
mechanisms underlying the genesis of these cells remain to be elucidated, the
field of cell-based therapeutics to treat T1D has advanced to the point where the
first Phase I/II trials in humans have begun. Here, we provide a concise review
of the history of cell replacement therapies to treat T1D from islet
transplantations and xenotranplantation, to current work in hESC/iPSC. We also
highlight the latest advances in efforts to employ insulin-producing, glucose
responsive beta-like cells derived from hESC as therapeutics.
PMID- 28702241
TI - The role of chloramines in treatment of diabetic foot ulcers: an exploratory
multicentre randomised controlled trial.
AB - BACKGROUND: Chronic foot ulcers in diabetes are serious, costly and frequently
difficult to heal. Recent guidelines conclude that new dressings and treatments
generally fail to show superiority compared with standard of care. Several
mechanisms are probably responsible for impaired healing of chronic foot ulcers,
including inflammation and infection. Chloramines have presumed antiseptic and
antibacterial properties, and have shown to be a useful treatment in odontology.
METHODS: In an explorative open randomised controlled multi-centre study, we
compared chloramine-based treatment with current standard of care for 12 weeks
and follow-up for 24 weeks. Seventeen patients in each group, mean age about 70,
duration of diabetes > 20 years and foot ulcers about 1.5 years, completed the 12
weeks study. RESULTS: After 5 weeks, the difference between the groups in
relative reduction in ulcer area was statistically significant (p=0.016).
Absolute change in ulcer area was first statistically significant within the
chloraminetreated group after 2 weeks (p=0.026), after 8 weeks in the control
group (p=0.0023), with significant difference between groups after 5 weeks
(p=0.024). The approximate relative decrease per week was 19.4% (95%CI 12.2,
26.0; p<0.0001) in the chloramine-treated group and 11.7% (95%CI 6.4, 16.7;
p<0.0001; between-group difference p=0.083). After 9 weeks 7 patients had healed
in the chloraminetreated group, but only one in the control group (p=0.039).
There were no statistically significant differences in wound healing at 12 or 24
weeks, and no marked differences in signs of infection, pain, quality of life (EQ
5D), or incidence of adverse events. CONCLUSIONS: Chloramine-based treatment
seems to be efficacious, particularly in the early phase of the care of infected
diabetic foot ulcers. It is safe and easy to use, and could prove to be a
valuable addition in the treatment arsenal, providing non-surgical debridement.
Future studies will evaluate its role in wound care.
PMID- 28702242
TI - Lipoprotein (a), an independent cardiovascular risk marker.
AB - Epidemiological and genetic studies have identified elevated levels of
lipoprotein (a) ((Lp(a)) as a causal and independent risk factor for
cardiovascular diseases (CVD). The Lp(a)-induced increased risk of CVD may be
mediated by both its proatherogenic and prothrombotic mechanisms. Several
guidelines recommend screening of Lp(a) level; however, there are few treatment
options for the management of patients with elevated Lp(a). Several new
medications for Lp(a) are under development. PCSK9 inhibitors, apolipoprotein (a)
antisense, and apolipoprotein(B-100)-antisense mipomersen have shown promising
results. Lp(a) reduction will continue to be an active area of investigation.
PMID- 28702243
TI - Prevalence of Gestational Diabetes Mellitus in urban and rural Tamil Nadu using
IADPSG and WHO 1999 criteria (WINGS 6).
AB - BACKGROUND: To determine the prevalence of Gestational Diabetes Mellitus (GDM) in
urban and rural Tamil Nadu in southern India, using the International Association
of Diabetes and Pregnancy Study Groups (IADPSG) and the World Health Organization
(WHO) 1999 criteria for GDM. METHODS: A total of 2121 pregnant women were
screened for GDM from antenatal clinics in government primary health centres of
Kancheepuram district (n = 520) and private maternity centres in Chennai city in
Tamil Nadu (n = 1601) between January 2013 to December 2014. Oral glucose
tolerance tests (OGTT) were done after an overnight fast of at least 8 h, using a
75 g glucose load and venous samples were drawn at 0, 1 and 2 h. GDM was
diagnosed using both the IADPSG criteria as well as the WHO 1999 criteria for
GDM. RESULTS: The overall prevalence of GDM after adjusting for age, BMI, family
history of diabetes and previous history of GDM was 18.5 % by IADPSG criteria
with no significant urban/rural differences (urban 19.8 % vs rural 16.1 %, p =
0.46). Using the WHO 1999 criteria, the overall adjusted prevalence of GDM was
14.6 % again with no significant urban/rural differences (urban 15.9 % vs rural
8.9 %, p = 0.13). CONCLUSION: The prevalence of GDM by IADPSG was high both using
IADPSG as well as WHO 1999 criteria with no significant urban/rural differences.
This emphasizes the need for increasing awareness about GDM and for prevention of
GDM in developing countries like India.
PMID- 28702244
TI - Treatment of Nonalcoholic Fatty Liver Disease (NAFLD) in patients with Type 2
Diabetes Mellitus.
AB - Nonalcoholic fatty liver disease (NAFLD) is believed to be the most common
chronic liver disease, affecting at least one-third of the population worldwide.
The more aggressive form is known as nonalcoholic steatohepatitis (NASH) and
characterized by hepatocyte necrosis and inflammation. The presence of fibrosis
is not uncommon. Fibrosis indicates a more aggressive course and patients with
NASH that are at high-risk of cirrhosis and premature mortality, as well as at
increased risk of hepatocellular carcinoma (HCC). Patients with type 2 diabetes
mellitus (T2DM) are at the highest risk for the development of NASH, even in the
setting of normal plasma aminotransferase levels. The presence of dysfunctional
adipose tissue in most overweight and obese subjects, combined with insulin
resistance, hyperglycemia, and atherogenic dyslipidemia, contribute to their
increased cardiovascular risk. Many therapeutic agents have been tested for the
treatment of NASH but few studies have focused in patients with T2DM. At the
present moment, the only FDA-approved agents that in controlled studies have
shown to significantly improve liver histology in patients with diabetes are
pioglitazone and liraglutide. Current research efforts are centering on the
mechanisms for intrahepatic triglyceride accumulation and for the development of
steatohepatitis, the role of mitochondrial dysfunction in NASH, and the impact of
improving glycemic control per se on the natural history of the disease. This
brief review summarizes our current knowledge on the pharmacological agents
available for the treatment of NASH to assist healthcare providers in the
management of these challenging patients.
PMID- 28702245
TI - Hyperglucagonemia in an animal model of insulin- deficient diabetes: what therapy
can improve it?
AB - BACKGROUND: Intra-islet insulin contributes to alpha-cell suppression. Akita mice
carry a toxic-gain-of- function Ins2 gene mutation encoding proinsulin-C(A7)Y,
similar to that described in human Mutant Ins-gene induced Diabetes of Youth,
which decreases intra-islet insulin. Herein, we examined Akita mice for
examination of circulating insulin and circulating glucagon levels. The
possibility that loss of intra-islet suppression of alpha-cells, with increased
circulating glucagon, contributes to diabetes under conditions of intra-islet
insulin deficiency, raises questions about effective treatments that may be
available. METHODS: Blood glucose, plasma insulin, C-peptide I, C-peptide II, and
glucagon were measured at various times during development of diabetes in Akita
mice. We also used Akita- like hProC(A7)Y-CpepGFP transgenic mice in Ins2+/+ ,
Ins2+/- and Ins2-/- genetic backgrounds (providing animals with greater or lesser
defects in islet insulin production, respectively) in order to examine the
relative abundance of immunostainable intra-islet glucagon-positive and insulin
positive cells. Similar measurements were made in Akita mice. Finally, the
effects of treatment with insulin, exendin-4, and leptin on blood glucose were
then compared in Akita mice. RESULTS: Interestingly, total insulin levels in the
circulation were not frankly low in Akita mice, although they did not rise
appropriately with the onset of hyperglycemia. By contrast, in severely diabetic
Akita mice at 6 weeks of age, circulating glucagon levels were significantly
elevated. Additionally, in Ins2+/- and Ins2-/- mice bearing the Akita-like
hProC(A7)Y-CpepGFP transgene, development of diabetes correlated with an increase
in the relative intra-islet abundance of immunostainable glucagon-positive cells,
and a similar observation was made in Akita islets. In Akita mice, whereas a
brief treatment with exendin-4 resulted in no apparent improvement in
hyperglycemia, leptin treatment resulted in restoration of normoglycemia.
Curiously, leptin treatment also suppressed circulating glucagon levels.
CONCLUSIONS: Loss of insulin-mediated intra-islet suppression of glucagon
production may be a contributor to hyperglycemia in Akita mice, and leptin
treatment appears beneficial in such a circumstance. This treatment might also be
considered in some human diabetes patients with diminished insulin reserve.
PMID- 28702246
TI - Cardiovascular safety assessment of pramlintide in type 2 diabetes: results from
a pooled analysis of five clinical trials.
AB - BACKGROUND: This report evaluated the cardiovascular safety of the amylin analog
pramlintide-an existing diabetes injectable treatment-by comparing relevant
cardiovascular adverse events (AEs) reported in previous phase 3 and 4 clinical
trials among patients receiving pramlintide and those receiving control
treatments. METHODS: Cardiovascular safety of pramlintide was assessed using
accepted regulatory medical definitions of AEs reported in five randomized,
controlled phase 3 and 4 trials of 16-52 weeks' duration in adults with type 2
diabetes. The original trials compared pramlintide (90-120 mcg twice daily or 30
150 mcg three times daily) with placebo (four studies) or a mealtime rapid-acting
insulin analog (one study). Background therapies included insulin alone or in
combination with oral glucose-lowering agents. AE data obtained from clinical
study reports were combined into one database and analyzed for the intention-to
treat population of 2016 patients (pramlintide, n = 1434; pooled comparator, n =
582). The primary analysis compared reported major adverse cardiovascular events
(MACE) between pramlintide and control. RESULTS: The incidence of reported MACE
was similar between pramlintide (4.7 %) and pooled comparators (4.5 %). Secondary
analyses included MACE relative risk and hazard ratio point estimates, which
ranged from 0.86 to 0.93 for pramlintide relative to comparator treatment; the
upper limit of the two-sided 95 % confidence interval did not exceed the
threshold of 1.8. CONCLUSIONS: Both the point estimate of the reported MACE
frequency and estimated risk ratios showed that mealtime pramlintide as an
adjunct to insulin conferred no increased risk of cardiovascular AEs in patients
with type 2 diabetes using insulin.
PMID- 28702247
TI - Screening and diagnosis of gestational diabetes mellitus - relevance to low and
middle income countries.
AB - Gestational diabetes mellitus (GDM) is one of the most common metabolic
complications of pregnancy. Ever since the first systematic evaluation of the
oral glucose tolerance test by O'Sullivan and colleagues was carried out in 1964,
there has been controversy with respect to the optimal screening and diagnostic
criteria to detect GDM. The recently proposed International Association of
Diabetes and Pregnancy Study Groups (IADPSG) criteria for GDM has found fairly
widespread acceptance, but it is still debated by several societies. This review
intends to provide an overview of the evolution of the screening and diagnostic
criteria for GDM. Debatable issues regarding optimal screening strategies,
especially in the low resource settings of low and middle income countries are
highlighted. The recent Women in India with GDM Strategy (WINGS) project carried
out in Chennai, India tried to develop a Model of Care for GDM suitable for
resource constrained settings. The findings related to screening and diagnosis of
GDM based on WINGS are also highlighted in this review. Based on the WINGS
experience we believe that despite the constraints in low and middle income
countries at the present time, the IADPSG criteria appears to be the best. This
will also help to bring out a uniform criteria for screening and diagnosis of GDM
worldwide.
PMID- 28702248
TI - Diabetes and other endocrine-metabolic abnormalities in the long-term follow-up
of pancreas transplantation.
AB - Pancreas transplantation (PTX) has been demonstrated to restore long-term glucose
homeostasis beyond what can be achieved by intensive insulin therapy or islet
transplants. Moreover, PTX has been shown to decrease the progression of the
chronic complications of diabetes. However, PTX patients require chronic use of
immunosuppressive drugs with potential side effects. The long-term follow-up of
PTX patients demands special care regarding metabolic deviations, infectious
complications, and chronic rejection. Diabetes and other endocrine metabolic
abnormalities following transplantation are common and can increase morbidity and
mortality. Previous recipient-related and donor-related factors, as well as other
aspects inherent to the transplant, act together in the pathogenesis of those
abnormalities. Early recognition of these disturbances is the key to timely
treatment; however, adequate tools to achieve this goal are often lacking. In a
way, the type of PTX procedure, whether simultaneous pancreas kidney or not,
seems to differentially influence the evolution of endocrine and metabolic
abnormalities. Further studies are needed to define the best approach for PTX
patients. This review will focus on the most common endocrine metabolic disorders
seen in the long-term management of PTX: diabetes mellitus, hyperlipidemia, and
bone loss. The authors here cover each one of these endocrine topics by showing
the evaluation as well as proper management in the follow-up after PTX.
PMID- 28702249
TI - Hypophysitis: Evaluation and Management.
AB - Hypophysitis is the acute or chronic inflammation of the pituitary gland. The
spectrum of hypophysitis has expanded in recent years with the addition of two
histologic subtypes and recognition as a complication of treatment with immune
checkpoint inhibitors. Despite the increased number of published cases, the
pathogenesis of hypophysitis is poorly understood, and treatment strategies are
diverse and controversial. The diagnosis of hypophysitis generally requires
histopathologic confirmation. The presentation and clinical course of
hypophysitis varies. Hypophysitis can resolve spontaneously, relapse may occur,
and some cases can be refractory to treatment.
PMID- 28702250
TI - Update on medical treatment for Cushing's disease.
AB - Cushing's disease (CD) is the most common cause of endogenous Cushing's syndrome
(CS). The goal of treatment is to rapidly control cortisol excess and achieve
long-term remission, to reverse the clinical features and reduce long-term
complications associated with increased mortality. While pituitary surgery
remains first line therapy, pituitary radiotherapy and bilateral adrenalectomy
have traditionally been seen as second-line therapies for persistent
hypercortisolism. Medical therapy is now recognized to play a key role in the
control of cortisol excess. In this review, all currently available medical
therapies are summarized, and novel medical therapies in phase 3 clinical trials,
such as osilodrostat and levoketoconazole are discussed, with an emphasis on
indications, efficacy and safety. Emerging data suggests increased efficacy and
better tolerability with these novel therapies and combination treatment
strategies, and potentially increases the therapeutic options for treatment of
CD. New insights into the pathophysiology of CD are highlighted, along with
potential therapeutic applications. Future treatments on the horizon such as R
roscovitine, retinoic acid, epidermal growth factor receptor inhibitors and
somatostatin-dopamine chimeric compounds are also described, with a focus on
potential clinical utility.
PMID- 28702251
TI - Thyroid nodule update on diagnosis and management.
AB - Thyroid nodules are common. The clinical importance of thyroid nodules is related
to excluding malignancy (4.0 to 6.5% of all thyroid nodules), evaluate their
functional status and assess for the presence of pressure symptoms. Incidental
thyroid nodules are being diagnosed with increasing frequency in the recent years
with the use of newer and highly sensitive imaging techniques. The high
prevalence of thyroid nodules necessitates that the clinicians use evidence-based
approaches for their assessment and management. New molecular tests have been
developed to help with evaluation of malignancy in thyroid nodules. This review
addresses advances in thyroid nodule evaluation, and their management considering
the current guidelines and supporting evidence.
PMID- 28702252
TI - Challenges in diagnosis and management of diabetes in the young.
AB - The prevalence of diabetes in children and adolescents is increasing worldwide,
with profound implications on the long-term health of individuals, societies, and
nations. The diagnosis and management of diabetes in youth presents several
unique challenges. Although type 1 diabetes is more common among children and
adolescents, the incidence of type 2 diabetes in youth is also on the rise,
particularly among certain ethnic groups. In addition, less common types of
diabetes such as monogenic diabetes syndromes and diabetes secondary to
pancreatopathy (in some parts of the world) need to be accurately identified to
initiate the most appropriate treatment. A detailed patient history and physical
examination usually provides clues to the diagnosis. However, specific laboratory
and imaging tests are needed to confirm the diagnosis. The management of diabetes
in children and adolescents is challenging in some cases due to age-specific
issues and the more aggressive nature of the disease. Nonetheless, a patient
centered approach focusing on comprehensive risk factor reduction with the
involvement of all concerned stakeholders (the patient, parents, peers and
teachers) could help in ensuring the best possible level of diabetes control and
prevention or delay of long-term complications.
PMID- 28702253
TI - Update on thyroid-associated Ophthalmopathy with a special emphasis on the ocular
surface.
AB - Thyroid-associated ophthalmopathy (TAO) is a condition associated with a wide
spectrum of ocular changes, usually in the context of the autoimmune syndrome,
Graves' disease. In this topical review, we attempted to provide a roadmap of the
recent advances in current understanding the pathogenesis of TAO, important
aspects of its clinical presentation, its impact on the ocular surface, describe
the tissue abnormalities frequently encountered, and describe how TAO is managed
today. We also briefly review how increased understanding of the disease should
culminate in improved therapies for patients with this vexing condition.
PMID- 28702254
TI - Can a single interactive seminar durably improve knowledge and confidence of
hospital diabetes management?
AB - BACKGROUND: Safe and effective diabetes management in the hospital is
challenging. Inadequate knowledge has been identified by trainees as a key
barrier. In this study we assess both the short-term and long-term impact of an
interactive seminar on medical student knowledge and comfort with hospital
diabetes management. METHODS: An interactive seminar covering hospital diabetes
management and utilizing an audience response system was added to the third-year
medical student curriculum. Students were given a multiple choice assessment
immediately before and after the seminar to assess their comprehension of the
material. Students were also asked to rate their confidence on this topic.
Approximately 6 months later, students were given the same assessment to
determine if the improvements in hospital diabetes knowledge and confidence were
durable over time. Students from the preceding medical school class, who did not
have a hospital diabetes seminar as a part of their curriculum, were used as a
control. RESULTS: Fifty-three students participated in the short-term assessment
immediately before and after the seminar. The mean score (maximum 15) was 7.7 +/-
2.7 (51%) on the pre-test and 11.4 +/- 1.8 (76%) on the post-test (p < 0.01). 75
students who attended the seminar completed the same set of questions 6 months
later with mean score of 9.2 +/- 2.3 (61%). The control group of 100 students who
did not attend seminar had a mean score of 8.8 +/- 2.5 (58%). The difference in
scores between the students 6-months after the seminar and the control group was
not significantly different (p = 0.30). CONCLUSIONS: Despite initial short-term
gains, a single seminar on hospital diabetes management did not durably improve
trainee knowledge or confidence. Addition of repeated and focused interactions
during clinical rotations or other sustained methods of exposure need to be
evaluated.
PMID- 28702255
TI - Diabetes and its drivers: the largest epidemic in human history?
AB - The "Diabesity" epidemic (obesity and type 2 diabetes) is likely to be the
biggest epidemic in human history. Diabetes has been seriously underrated as a
global public health issue and the world can no longer ignore "the rise and rise"
of type 2 diabetes. Currently, most of the national and global diabetes estimates
come from the IDF Atlas. These estimates have significant limitations from a
public health perspective. It is apparent that the IDF have consistently
underestimated the global burden. More reliable estimates of the future burden of
diabetes are urgently needed. To prevent type 2 diabetes, a better understanding
of the drivers of the epidemic is needed. While for years, there has been
comprehensive attention to the "traditional" risk factors for type 2 diabetes
i.e., genes, lifestyle and behavioral change, the spotlight is turning to the
impact of the intra-uterine environment and epigenetics on future risk in adult
life. It highlights the urgency for discovering novel approaches to prevention
focusing on maternal and child health. Diabetes risk through epigenetic changes
can be transmitted inter-generationally thus creating a vicious cycle that will
continue to feed the diabetes epidemic. History provides important lessons and
there are lessons to learn from major catastrophic events such as the Dutch
Winter Hunger and Chinese famines. The Chinese famine may have been the trigger
for what may be viewed as a diabetes "avalanche" many decades later. The drivers
of the epidemic are indeed genes and environment but they are now joined by
deleterious early life events. Looking to the future there is the potential
scenario of future new "hot spots" for type 2 diabetes in regions e.g., the Horn
of Africa, now experiencing droughts and famine. This is likely to occur should
improved economic and living conditions occur over the next few decades. Type 2
diabetes will remain one of the greatest challenges to human health for many
years to come.
PMID- 28702256
TI - Physician knowledge of a rare foot condition - influence of diabetic patient
population on self-described knowledge and treatment.
AB - BACKGROUND: Charcot neuroarthopathy (CN), a rare foot and ankle condition usually
complicating diabetes mellitus, leads to deformity, poor quality of life, and
increased mortality and morbidity. The prevalence of this condition in the
diabetic patient population is not currently known but has been reportedly
misdiagnosed in up to 95% of cases. METHODS: We sought to evaluate general
knowledge regarding CN in non-foot specialist clinical faculty at a large
academic institution and to understand their practice habits. Our survey
emphasizes the necessity of better education surrounding CN to improve outcomes
in a preventative fashion. This will enable us to determine how to focus
educational forums surrounding this topic in the future. RESULTS: Seven hundred
eighty-nine faculty members were sent the survey while 400 completed the survey
for a response rate of 50.7%. The respondents were representative of academic
rank at the institution and were comprised of endocrinologists, internal medicine
physicians and family medicine physicians. We found that 67.6% of responders had
a self-described poor or complete lack of knowledge of this condition. Clinicians
with self-described better knowledge of CN were more likely to provide a correct
initial management of CN (p < 0.001; r = 0.3639). CONCLUSIONS: In this large
tertiary institution, a majority of providers among internal medicine,
endocrinologists, and family medicine physicians demonstrated minimal or no
knowledge of this rare, but potentially devastating diabetes complication.
However, those providers who are knowledgeable of CN, performed better in the
initial management of this condition. Also, respondents who treated more diabetic
patients demonstrated an association with correct management. Education, and the
development of better understanding amongst clinicians, is crucial to limit the
devastating effects of this condition in the future.
PMID- 28702257
TI - The relationship between diabetes mellitus and 30-day readmission rates.
AB - BACKGROUND: It is estimated that 9.3% of the population in the United States have
diabetes mellitus (DM), 28% of which are undiagnosed. The high prevalence of DM
makes it a common comorbid condition in hospitalized patients. In recent years,
government agencies and healthcare systems have increasingly focused on 30-day
readmission rates to determine the complexity of their patient populations and to
improve quality. Thirty-day readmission rates for hospitalized patients with DM
are reported to be between 14.4 and 22.7%, much higher than the rate for all
hospitalized patients (8.5-13.5%). The objectives of this study were to (1)
determine the incidence and causes of 30-day readmission rates for patients with
diabetes listed as either the primary reason for the index admission or with
diabetes listed as a secondary diagnosis compared to those without DM and (2)
evaluate the impact on readmission of two specialized inpatient DM services: the
Hyperglycemic Intensive Insulin Program (HIIP) and Endocrine Consults (ENDO).
METHODS: For this study, DM was defined as any ICD-9 discharge diagnosis
(principal or secondary) of 250.xx. Readmissions were defined as any unscheduled
inpatient admission, emergency department (ED) visit, or observation unit stay.
We analyzed two separate sets of patient data. The first pilot study was a
retrospective chart review of all patients with a principle or secondary
admission diagnosis of diabetes admitted to any adult service within the
University of Michigan Health System (UMHS) between October 1, 2013 and December
31, 2013. We then did further uncontrolled analysis of the patients with a
principal admitting diagnosis of diabetes. The second larger retrospective study
included all adults discharged from UMHS between October 1, 2013 and September
30, 2014 with principal or secondary discharge diagnosis of DM (ICD-9-CM:
250.xx). RESULTS: In the pilot study of 7763 admissions, the readmission rate was
26% for patients with DM and 22% for patients without DM. In patients with a
primary diagnosis of DM on index admission, the most common cause for readmission
was DM-related. In the larger study were 37,702 adult inpatient discharges
between October 1, 2013 and September 30, 2014. Of these, 20.9% had DM listed as
an encounter diagnosis. Rates for all encounters (inpatient, ED and Observation
care) were 24.3% in patients with DM compared to 17.7% in those without DM (p <
0.001). The most common cause for readmission in patients with DM as a secondary
diagnosis to the index admission was infection-related. During the index hospital
stay, only a small proportion of patients with DM (approximately 12%) received
any DM service consult. Those who received a DM consult had a higher case mix
index compared to those who did not. Despite the higher acuity, there was a lower
rate of ED /observation readmission in patients followed by the DM services (6.6%
HIIP or ENDO vs. 9.6% no HIIP or ENDO, p = 0.0012), though no difference in the
inpatient readmission rates (17.6% HIIP or ENDO vs. 17.4% no HIIP or ENDO, p =
0.89) was noted. CONCLUSIONS: Patients with both a primary or secondary diagnosis
of DM have higher readmission rates. The reasons for readmission vary; patients
with a principal diagnosis of DM have more DM related readmissions and those with
secondary diagnosis having more infection-related readmissions. DM services were
used in a small proportion of patients and may have contributed to lower DM
related ED revisits. Further prospective studies evaluating the role of these
services in terms of glucose management, patient education and outpatient follow
up on readmission are needed to identify interventions important to reducing
readmission rates.
PMID- 28702259
TI - Clinical effects, cardiovascular and renal outcomes associated with rapid-acting
insulin analogs among individuals with type 2 diabetes: a nation-wide
observational cohort study.
AB - BACKGROUND: Rapid-acting insulin analogs (RAIs) have not been examined for long
term safety in randomized clinical trials. We performed a nationwide longitudinal
cohort study among individuals with type 2 diabetes (T2DM) to address
cardiovascular safety and mortality among users of lispro, aspart and glulisine
insulins. METHODS: We used four national registers, following patients previously
not treated with RAI but with continuous use of RAIs in 2005-2014 up to 6.4
years, to examine HbA1c and weight, and the occurrence of severe hyperglycemia or
hypoglycemia, renal failure, cardiovascular events or death. The treatment groups
were compared using a weighted Cox proportional hazards model. RESULTS: We
included 17,620 patients, mean age slightly higher than 60 years, diabetes
duration 9.9-11.7 years, mean BMI 30.5 kg/m2, HbA1c around 70 mmol/mol (8.6%
NGSP), and 40.9-54.0% of the patients exhibiting eGFR <60 ml/min/1.73 m2 in the
three groups. Around 95% of the patients also used another insulin, and 24.2
24.7% had a history of cardiovascular disease (CVD). Mean HbA1c and weight levels
were stable and similar. Incidence rates of death were 234.4, 284.9 and 156.7 per
1000 person-years among users of lispro, aspart, and glulisine; incidence rates
of all cardiovascular events were 668.4, 622.4, and 699.5 per 1000 person-years,
respectively. There were no differences in mortality, CVD, renal failure or
severe hypoglycemia or hyperglycemia, although a lower mortality risk in patients
on glulisine compared with aspart, and lower risk of stroke in users of glulisine
was suggested. The risk of severe hyperglycemia was higher with lispro than
aspart, and lower of severe hypoglycemia than aspart or glulisine among the older
age group. CONCLUSIONS: Overall, there do not appear to be any major important
differences in effects on hypoglycemia, hyperglycemia, weight or long-term safety
between the three available RAIs among insulin-naive individuals with T2DM in
clinical practice.
PMID- 28702258
TI - Peer support of complex health behaviors in prevention and disease management
with special reference to diabetes: systematic reviews.
AB - OBJECTIVES: Examine Peer Support (PS) for complex, sustained health behaviors in
prevention or disease management with emphasis on diabetes prevention and
management. DATA SOURCES AND ELIGIBILITY: PS was defined as emotional,
motivational and practical assistance provided by nonprofessionals for complex
health behaviors. Initial review examined 65 studies drawn from 1442 abstracts
identified through PubMed, published 1/1/2000-7/15/2011. From this search, 24
reviews were also identified. Extension of the search in diabetes identified 30
studies published 1/1/2000-12/31/2015. RESULTS: In initial review, 54 of all 65
studies (83.1%) reported significant impacts of PS, 40 (61.5%) reporting between
group differences and another 14 (21.5%) reporting significant within-group
changes. Across 19 of 24 reviews providing quantifiable findings, a median of
64.5% of studies reviewed reported significant effects of PS. In extended review
of diabetes, 26 of all 30 studies (86.7%) reported significant impacts of PS, 17
(56.7%) reporting between-group differences and another nine (30.0%) reporting
significant within-group changes. Among 19 of these 30 reporting HbA1c data,
average reduction was 0.76 points. Studies that did not find effects of PS
included other sources of support, implementation or methodological problems,
lack of acceptance of interventions, poor fit to recipient needs, and possible
harm of unmoderated PS. CONCLUSIONS: Across diverse settings, including under
resourced countries and health care systems, PS is effective in improving complex
health behaviors in disease prevention and management including in diabetes.
PMID- 28702260
TI - Renin Angiotensin system-modifying therapies are associated with improved
pulmonary health.
AB - BACKGROUND: Pulmonary diseases are often complicated and have diverse etiologies.
One common factor is the lack of therapeutics available for these diseases. The
goal of this study was to investigate the impact of Renin-Angiotensin System
(RAS)-modifying medications on incidence and time to pulmonary complications.
METHODS: A retrospective analysis was conducted using claims data from a US
commercial insurance company (2007-2013). The study consisted of patients with an
emerging hypertension (HTN) diagnosis. Cox analysis was used to look at the
effect of angiotensin converting enzyme inhibitors (ACE-Is) and angiotensin
receptor blockers (ARBs) in this population. The events included pneumonia and
influenza (infectious), Chronic obstructive pulmonary disease (COPD) and allied
conditions (inflammatory), and other diseases (structural). RESULTS: A total of
215,225 patients were followed in the study. These fell into three groups
depending on the first prescribed anti-hypertension medication; ACE-Is (47.21%),
ARBs (11.40%) and calcium channel blockers (CCBs)/Diuretics-Control (41.39%). The
use of ACE-I as first treatment significantly reduced the incidence of infectious
(Hazard Ratio (HR) 0.886, 95% Confidence Interval (95% CI) 0.859-0.886),
inflammatory (HR 0.924, 95% CI 0.906-0.942) and structural outcomes (HR 0.865,
95% CI 0.847-0.885); it also increased the time (delayed) to diagnosis with
prolonged treatment. Primary ARB use only significantly lowered the incidence of
structural outcomes (HR 0.900, 95% CI 0.868-0.933); prolonged treatment did
reduce incidence of all three diagnosis groups and significantly delayed disease
onset. CONCLUSIONS: There is an association between the use of ACE-Is and ARBs
and a delay in the progression of pulmonary complications in vulnerable
populations. Research into the RAS may identify future therapies for patients
with potential chronic pulmonary conditions.
PMID- 28702261
TI - Macular findings in Spectral Domain Optical Coherence Tomography and OCT
Angiography in a patient with Kearns-Sayre syndrome.
AB - BACKGROUND: To report the clinical, electrophysiological and the anatomical
findings in a patient with Kearns-Sayre syndrome (KSS). CASE PRESENTATION: We
present the case of a 55-year-old female with KSS, who developed systemic
features and ocular manifestations as ophthalmoplegia and retinal dysfunction,
that were corroborated by electrophysiological test and High Definition Spectral
Domain Optical Coherence Tomography (HD SD OCT) and OCT-Angiography (OCT-A).
CONCLUSION: We report a patient with KSS, accompanied by some alterations of the
RPE and photoreceptors observed in the external HD SD OCT and OCT-A. In the best
of our knowledge, this is the first report in the literature of HD SD OCT
findings in a patient with KSS.
PMID- 28702262
TI - Hemispheric Asymmetry of Development Due to Drug Exposure.
AB - BACKGROUND: A previous survey of the literature of fMRI brain activation for two
risk factors, impulsivity and craving, for addiction were lateralized to the
right and left hemispheres respectively. Most articles reported these findings
without consideration of how lateral asymmetries might be relevant to
understanding the underlying factors leading to addiction. OBJECTIVE: The current
survey is intended to extend these observations by demonstrating hemispheric
asymmetry of development due to pre-natal or adolescent/adult exposure to drugs
of abuse. METHOD: Articles that reported either pre-natal or adolescent/adult
exposure to drugs of abuse were collected and the hemisphere of the affected
structures was tabulated to determine if, and which, drugs affected more
structures in one hemisphere or the other or both together. RESULTS: Some drugs,
notably cocaine and alcohol, differentially affected left or right hemisphere
structures which significantly differed depending on whether individuals were
exposed prenatally or as an adolescent/adult. Cocaine tended to affect more left
hemisphere structures when exposed prenatally and significantly affected more in
the right when exposed as adults. Alcohol had the reverse pattern. The difference
in patterns of effect between pre-natal or adult exposure was significant for
both. CONCLUSION: The results in this survey demonstrate that some drugs of abuse
appear to have a right/left differential effect on structures of the brain.
Further investigation into the reasons for this asymmetry may provide new
insights into underlying factors of drug-seeking and addiction.
PMID- 28702263
TI - Factors Associated with the Incidence and Severity of New-Onset Atrial
Fibrillation in Adult Critically Ill Patients.
AB - BACKGROUND: Acute Atrial Fibrillation (AF) is common in critically ill patients,
with significant morbidity and mortality; however, its incidence and severity in
Intensive Care Units (ICUs) from low-income countries are poorly studied.
Additionally, impact of vasoactive drugs on its incidence and severity is still
not understood. This study aimed to assess epidemiology and risk factors for
acute new-onset AF in critically ill adult patients and the role of vasoactive
drugs. METHOD: Cohort performed in seven general ICUs (including cardiac surgery)
in three cities in Parana State (southern Brazil) for 45 days. Patients were
followed until hospital discharge. RESULTS: Among 430 patients evaluated, the
incidence of acute new-onset AF was 11.2%. Patients with AF had higher ICU and
hospital mortality. Vasoactive drugs use (norepinephrine and dobutamine) was
correlated with higher incidence of AF and higher mortality in patients with AF;
vasopressin (though used in few patients) had no effect on development of AF.
CONCLUSIONS: In general ICU patients, incidence of new-onset AF was 11.2% with a
high impact on morbidity and mortality, particularly associated with the presence
of Acute Renal Failure. The use of vasoactive drugs (norepinephrine and
dobutamine) could lead to a higher incidence of new-onset AF-associated morbidity
and mortality.
PMID- 28702264
TI - Comparative Performance of Creatinine-Based Estimated Glomerular Filtration Rate
Equations in the Malays: A Pilot Study in Tertiary Hospital in Malaysia.
AB - AIM: To validate the accuracy of estimated glomerular filtration rate (eGFR)
equations in Malay population attending our hospital in comparison with
radiolabeled measured GFR. METHODS: A cross-sectional study recruiting
volunteered patients in the outpatient setting. Chromium EDTA (51Cr-EDTA) was
used as measured GFR. The predictive capabilities of Cockcroft-Gault equation
corrected for body surface area (CGBSA), four-variable Modification of Diet in
Renal Disease (4-MDRD), and Chronic Kidney Disease Epidemiology Collaboration
(CKD-EPI) equations were calculated. RESULTS: A total of 51 subjects were
recruited with mean measured GFR 42.04 (17.70-111.10) ml/min/1.73 m2. Estimated
GFR based on CGBSA, 4-MDRD, and CKD-EPI were 40.47 (16.52-115.52), 35.90 (14.00
98.00), and 37.24 (14.00-121.00), respectively. Higher accuracy was noted in 4
MDRD equations throughout all GFR groups except for subgroup of GFR >= 60
ml/min/1.73 m2 where CGBSA was better. CONCLUSIONS: The 4-MDRD equation seems to
perform better in estimating GFR in Malay CKD patients generally and specifically
in the subgroup of GFR < 60 ml/min/1.73 m2 and both BMI subgroups.
PMID- 28702265
TI - Rehabilitation of Nose following Chemical Burn Using CAD/CAM Made Substructure
for Implant Retained Nasal Prosthesis: A Clinical Report.
AB - Insufficient knowledge of medical chemicals and their improper use have
destructive effects. Accidental exposure to chemicals on facial tissue may result
in large facial defect. For ages the tradition of piercing nose is common but
improper use of unknown chemical for piercing has deleterious effect. Mostly
rhinectomy defects are acquired caused by trauma or malignant diseases.
Prosthetic rehabilitation is the preferred treatment of choice for any large
rhinectomy defects as medical and surgical interventions are ineffective in
developing esthetics. Main concern with the prosthesis for such defects is
retention. This article describes rehabilitation of a patient with large size
nasal defect created by chemical burn in childhood during piercing. Implant
retained customized silicone nasal prosthesis was fabricated using simple O-ring
attachments and innovative modified polyamide acrylic resin substructure acting
as skeleton.
PMID- 28702266
TI - Papillary Thyroid Carcinoma: Ectopic Malignancy versus Metastatic Disease.
AB - Papillary thyroid carcinoma frequently metastasizes to regional lymph nodes.
However, cervical lymph node metastasis as a sole manifestation of occult
papillary thyroid carcinoma is rarely observed. Ectopic thyroid is an uncommon
condition defined as the presence of thyroid tissue at a site other than
pretracheal area. Approximately 1-3% of all ectopic thyroid tissue is located in
the lateral neck. This entity may represent the only functional thyroid tissue in
the body. Malignant transformation of ectopic thyroid is uncommon; but even rarer
is the development of papillary carcinoma on it. We present a case of a 33-year
old man with an incidental lateral neck mass diagnosed after a motor vehicle
accident. Total thyroidectomy and lymph node resection were completed without
evidence of papillary thyroid carcinoma. Malignant transformation of heterotopic
thyroid tissue was the final diagnosis. The possibility of an ectopic thyroid
cancer should be considered in the differential diagnosis of a pathological mass
in the neck. The uniqueness of this case strives in the rarity that the thyroid
gland was free of malignancy, despite ectopic tissue being positive for thyroid
carcinoma. Management strategies, including performance of total thyroidectomy,
neck dissection, and treatment with radioiodine, should be based on
individualized risk assessment.
PMID- 28702267
TI - Total Parenteral Nutrition Successfully Treating Black Esophagus Secondary to
Hypovolemic Shock.
AB - We present a patient who developed black esophagus secondary to hypovolemic shock
and was placed on total parenteral nutrition for three weeks after hospital
discharge. The area of interest is the multimodal approach used in treatment of
this noncompliant patient. Even with a high mortality rate, this case illustrates
a successful outcome of a patient who responded to appropriate immediate therapy
resulting in complete resolution of the necrosis with no further development of
complications.
PMID- 28702268
TI - Distressing Visual Hallucinations after Treatment with Trazodone.
AB - Trazodone, a second-generation atypical antidepressant, is increasingly being
used off-label, in the treatment of insomnia. Although generally well tolerated,
trazodone treatment can be associated with some complications. We describe a case
of a 60-year-old man who received trazodone for primary insomnia. He returned, to
the emergency department, two days later with distressing visual hallucinations,
which prompted inpatient treatment. Trazodone was discontinued, leading to a
complete resolution of his visual hallucinations, and he was treated with
mirtazapine for 6 months. There has been no relapse in a follow-up period of two
years. Patients presenting with visual hallucinations without significant
psychiatry history can be a challenging situation. We highlight the importance of
careful anamnesis with an accurate medication history. Given the widespread use
of trazodone, clinicians should be aware of this possible side effect.
PMID- 28702269
TI - Marker-Negative Pheochromocytoma Associated with Inferior Vena Cava Thrombosis.
AB - Pheochromocytoma associated with inferior vena cava (IVC) thrombosis is very
rare. A 27-year-old female presented with right flank pain and hypertensive
urgency. Contrast-enhanced CT abdomen and gadolinium-contrast MRI abdomen
revealed right adrenal mass suspicious of malignancy with invasion and
compression to the right IVC wall along with IVC thrombus extending from the
level of renal veins to the level of confluence with hepatic veins. Her routine
laboratory investigations including 24-hour urine fractionated metanephrines,
vanillylmandelic acid, and cortisol were normal. Right adrenalectomy with IVC
thrombectomy was done. Perioperative period was uneventful. Histopathology of the
mass turned out to be pheochromocytoma with thrombus revealing fibroadipose
tissue with fibrin. Pheochromocytoma may present with IVC thrombus as well as
normal serum and urinary markers. Thus, clinical suspicion is imperative in
perioperative management of adrenal mass.
PMID- 28702270
TI - Prevalence and Risk Factors of Mortality among Adult HIV Patients Initiating ART
in Rural Setting of HIV Care and Treatment Services in North Western Tanzania: A
Retrospective Cohort Study.
AB - INTRODUCTION: HIV still causes high mortality despite use of ART. This study was
designed to determine the prevalence and risk factors of mortality among HIV
patients receiving ART in northwestern rural Tanzania. METHODS: A retrospective
study of HIV patients on ART was done at Sengerema in Mwanza, Tanzania. The data
on demography, date of HIV diagnosis, WHO stage, opportunistic infections, CD4,
hemoglobin, ART regimen, and time and outcome on treatment as dead or alive were
collected and analyzed using STATA version 11. RESULTS: In total, 740 patients
were studied. The median age was 35 (27-42) years with female predominance of 465
(62.8%). Of the participants, 261 (35.3%) had WHO stages 3 and 4 diseases. Most
participants, 258 (34.9%), had baseline CD4 counts <200 cells/MUl. Deaths
occurred in 86 (11.6%) patients which were independently associated with male
gender (16.0% versus 9.0%, p = 0.015), being divorced (OR = 2.7, p < 0.001), WHO
stages 3 and 4 (OR = 2.3, p = 0.05), CD4 <200 cells/MUl (OR = 3.4, p < 0.001),
and severe anemia (OR = 6.6, p < 0.001). CONCLUSIONS: The mortality is high among
HIV patients receiving ART in northwestern rural Tanzania. Universal testing
could increase early diagnosis and treatment. A close follow-up of at-risk
patients within the first year of ART could reduce the mortality of this subgroup
of patients.
PMID- 28702271
TI - Risk Factors and Etiology of Young Ischemic Stroke Patients in Estonia.
AB - OBJECTIVES: Reports on young patients with ischemic stroke from Eastern Europe
have been scarce. This study aimed to assess risk factors and etiology of first
ever and recurrent stroke among young Estonian patients. METHODS: We performed a
retrospective study of consecutive ischemic stroke patients aged 18-54 years who
were treated in our two hospitals from 2003 to 2012. RESULTS: We identified 741
patients with first-ever stroke and 96 patients with recurrent stroke. Among
first-time patients, men predominated in all age groups. The prevalence of well
documented risk factors in first-time stroke patients was 83% and in the
recurrent group 91%. The most frequent risk factors were hypertension (53%),
dyslipidemia (46%), and smoking (35%). Recurrent stroke patients had fewer less
well-documented risk factors compared to first-time stroke patients (19.8 versus
30.0%, P = 0.036). Atrial fibrillation was the most common cause of cardioembolic
strokes (48%) and large-artery atherosclerosis (LAA) was the cause in 8% among
those aged <35 years. Compared to first-time strokes, recurrent ones were more
frequently caused by LAA (14.3 versus 24.0%, P = 0.01) and less often by other
definite etiology (8.5 versus 1.0%, P = 0.01). CONCLUSIONS: The prevalence of
vascular risk factors among Estonian young stroke patients is high. Premature
atherosclerosis is a cause in a substantial part of very young stroke patients.
PMID- 28702272
TI - Immune Activation: Contribution to AIDS-Associated Non-Hodgkin Lymphoma.
AB - HIV infection is associated with a greatly elevated risk for the development of
non-Hodgkin lymphoma (NHL), which while diminished, remains elevated in the
highly active antiretroviral therapy (HAART) era. Chronic B cell activation,
driven by contact with HIV virions, B cell-stimulatory cytokines, viruses (EBV,
HPV, HCV), and by high levels of antigenic stimulation occurs in HIV infected
persons, and it is seen at even higher levels in those who go on to develop AIDS
NHL. Evidence from multiple studies indicates that elevated serum levels of
several B cell-stimulatory cytokines and biomarkers are seen preceding AIDS-NHL,
as well as in immunocompetent persons that develop NHL. Phenotypic changes in
circulating B cells also are seen preceding AIDS-NHL, including the expression of
AICDA, and of cell-surface molecules and miRNA that are associated with activated
B cells. HAART only partially normalizes the immune system of treated HIV+
persons as they still show clear evidence for ongoing inflammation and immune
activation in, even those who show complete suppression of HIV viremia. Together,
this provides ample evidence to support the notion that chronic activation of B
cells contributes to the genesis of B cell lymphomas.
PMID- 28702273
TI - The Arf activator GBF1 localizes to plasma membrane sites involved in cell
adhesion and motility.
PMID- 28702274
TI - Yeast chemotropism: A paradigm shift in chemical gradient sensing.
AB - The ability of cells to direct their movement and growth in response to shallow
chemical gradients is essential in the life cycles of all eukaryotic organisms.
The signaling mechanisms underlying directional sensing in chemotactic cells have
been well studied; however, relatively little is known about how chemotropic
cells interpret chemical gradients. Recent studies of chemotropism in budding and
fission yeast have revealed 2 quite different mechanisms-biased wandering of the
polarity complex, and differential internalization of the receptor and G protein.
Each of these mechanisms has been proposed to play a key role in decoding mating
pheromone gradients. Here we explore how they may work together as 2 essential
components of one gradient sensing machine.
PMID- 28702275
TI - Molting in C. elegans.
AB - Molting is an essential developmental process for the majority of animal species
on Earth. During the molting process, which is a specialized form of
extracellular matrix (ECM) remodeling, the old apical ECM, or cuticle, is
replaced with a new one. Many of the genes and pathways identified as important
for molting in nematodes are highly conserved in vertebrates and include
regulators and components of vesicular trafficking, steroid-hormone signaling,
developmental timers, and hedgehog-like signaling. In this review, we discuss
what is known about molting, with a focus on studies in Caenorhabditis elegans.
We also describe the key structural elements of the cuticle that must be
released, newly synthesized, or remodeled for proper molting to occur.
PMID- 28702276
TI - Radiation-induced translational control of gene expression.
AB - Radiation-induced gene expression has long been hypothesized to protect against
cell death. Defining this process would provide not only insight into the
mechanisms mediating cell survival after radiation exposure, but also a novel
source of targets for radiosensitization. However, whereas the radiation-induced
gene expression profiles using total cellular mRNA have been generated for cell
lines as well as normal tissues, with few exception, the changes in mRNA do not
correlate with changes in the corresponding protein. The traditional approach to
profiling gene expression, i.e., using total cellular RNA, does not take into
account posttranscriptional regulation. In this review, we describe the use of
gene expression profiling of polysome-bound RNA to establish that radiation
modifies gene expression via translational control. Because changes in polysome
bound mRNA correlate with changes in protein, analysis of the translational
profiles provides a unique data set for investigating the mechanisms mediating
cellular radioresponse.
PMID- 28702277
TI - Class II members of the poly(A) binding protein family exhibit distinct functions
during Arabidopsis growth and development.
AB - The poly(A)-binding protein (PABP) binds to the poly(A) tail of eukaryotic
cellular mRNAs and contributes to their stability and translational efficiency.
In plants, PABP is expressed from an unusually large gene family grouped into 3
classes that expanded during the evolution of land plants. Subsequent to
expansion of the family, members diverged in their primary sequence and in
expression. Further expansion of the family and divergence of its members in the
Brassicaceae demonstrate the continued dynamic evolution of PABP in plants. In
this study, the function of the widely-expressed class II PABP family members was
examined to determine how individual class II members contribute to plant growth
and development. Of the 3 class II PABP members, PAB2 and PAB4 contribute most to
vegetative growth and vegetative-to-floral transition whereas PAB2, and the
recently-evolved third class II member, PAB8, contribute to inflorescence and
silique growth. Interestingly, although class I and class III PABP members are
expressed specifically in reproductive organs, class II PABP members are also
necessary for fertility in that the combinatorial loss of PAB2 and either PAB4 or
PAB8 expression resulted in reduced fertility. Although all 3 class II members
are required for protein expression, PAB4 contributes most to the steady-state
level of a reporter mRNA and to protein expression. These findings suggest that
class II PABP members are partially overlapping in function but also involved in
distinct aspects of plant growth and development.
PMID- 28702278
TI - PRIMA: a gene-centered, RNA-to-protein method for mapping RNA-protein
interactions.
AB - Interactions between RNA binding proteins (RBPs) and mRNAs are critical to post
transcriptional gene regulation. Eukaryotic genomes encode thousands of mRNAs and
hundreds of RBPs. However, in contrast to interactions between transcription
factors (TFs) and DNA, the interactome between RBPs and RNA has been explored for
only a small number of proteins and RNAs. This is largely because the focus has
been on using 'protein-centered' (RBP-to-RNA) interaction mapping methods that
identify the RNAs with which an individual RBP interacts. While powerful, these
methods cannot as of yet be applied to the entire RBPome. Moreover, it may be
desirable for a researcher to identify the repertoire of RBPs that can interact
with an mRNA of interest-in a 'gene-centered' manner-yet few such techniques are
available. Here, we present Protein-RNA Interaction Mapping Assay (PRIMA) with
which an RNA 'bait' can be tested versus multiple RBP 'preys' in a single
experiment. PRIMA is a translation-based assay that examines interactions in the
yeast cytoplasm, the cellular location of mRNA translation. We show that PRIMA
can be used with small RNA elements, as well as with full-length Caenorhabditis
elegans 3' UTRs. PRIMA faithfully recapitulated numerous well-characterized RNA
RBP interactions and also identified novel interactions, some of which were
confirmed in vivo. We envision that PRIMA will provide a complementary tool to
expand the depth and scale with which the RNA-RBP interactome can be explored.
PMID- 28702279
TI - The utilization of selenocysteine-tRNA[Ser]Sec isoforms is regulated in part at
the level of translation in vitro.
AB - The tRNA for the 21st proteinogenic amino acid, selenocysteine, exists in
mammalian cells as 2 isoforms differing by a single 2'-O-methylribosyl moiety at
position 34 (Um34). These isoforms contain either 5-methoxycarbonylmethyluridine
(mcm5U) or 5-methoxycarbonylmethyl-2'-O-methyluridine (mcm5Um) at position 34.
The accumulation of the mcm5Um isoform is tightly correlated with the expression
of nonessential "stress response" selenoproteins such as glutathione peroxidase 1
(GPX1). The expression of essential selenoproteins, such as thioredoxin reductase
1 (TXNRD1), is not affected by changes in Sec-tRNA[Ser]Sec isoform accumulation.
In this work we used purified mcm5U and mcm5Um Sec-tRNA[Ser]Sec isoforms to
analyze possible differences in binding to the selenocysteine-specific elongation
factor, EEFSEC, and the translation of GPX1 and TXNRD1in vitro. Our results
indicate that no major distinction between mcm5U and mcm5Um isoforms is made by
the translation machinery, but a small consistent increase in GPX1 translation is
associated with the mcm5Um isoform. These results implicate fundamental
differences in translation efficiency in playing a role in regulating
selenoprotein expression as a function of isoform accumulation.
PMID- 28702280
TI - Dissecting limiting factors of the Protein synthesis Using Recombinant Elements
(PURE) system.
AB - Reconstituted cell-free protein synthesis systems such as the Protein synthesis
Using Recombinant Elements (PURE) system give high-throughput and controlled
access to in vitro protein synthesis. Here we show that compared with the
commercial S30 crude extract based RTS 100 E. coli HY system, the PURE system has
less mRNA degradation and produces up to ~6-fold full-length proteins. However
the majority of polypeptides PURE produces are partially translated or inactive
since the signal from firefly luciferase (Fluc) translated in PURE is only ~2/3rd
of that measured using the RTS 100 E. coli HY S30 system. Both of the 2 batch
systems suffer from low ribosome recycling efficiency when translating proteins
from 82 kD to 224 kD. A systematic fed-batch analysis of PURE shows replenishment
of 6 small molecule substrates individually or in combination before energy
depletion increased Fluc protein yield by ~1.5 to ~2-fold, while creatine
phosphate and magnesium have synergistic effects when added to the PURE system.
Additionally, while adding EF-P to PURE reduced full-length protein translated,
it increased the fraction of functional protein and reduced partially translated
protein probably by slowing down the translation process. Finally, ArfA, rather
than YaeJ or PrfH, helped reduce ribosome stalling when translating Fluc and
improved system productivity in a template-dependent fashion.
PMID- 28702281
TI - How best to determine causative pathogens of pneumonia.
AB - The biggest recent development in pneumonia diagnostics has been the increased
availability and use of nucleic acid detection assays, although this change has
brought with it new challenges about the interpretation of positive results.
Recognition of the existence of the lung microbiome has challenged the
traditional views of pneumonia pathogenesis and may provide the opportunity for
new diagnostic tools that are focused on more than just detection of specific
known pathogens.
PMID- 28702282
TI - Non-infectious mimics of community-acquired pneumonia.
AB - Community-acquired pneumonia (CAP) is a common cause of presentation to
healthcare facilities. The diagnosis of CAP is usually made in patients with
suggestive symptoms, signs, and radiological features. A number of non-infectious
conditions, including neoplastic lesions, pulmonary oedema, pulmonary embolism,
drug-induced pneumonitis, diffuse alveolar haemorrhage syndromes, cryptogenic
organising pneumonia and acute eosinophilic pneumonia, may present in a similar
way and mimic CAP. These other conditions are often only thought of after
patients that are being treated as CAP fail to respond to therapy. The non
infectious mimics of CAP require early diagnosis and appropriate treatment to
decrease patient morbidity and mortality. This article is intended to create an
awareness of the non-infectious mimics of CAP and highlight some of the more
frequent conditions as well as those that require early diagnosis and treatment
to prevent a poor outcome.
PMID- 28702283
TI - Neonatal pneumonia in sub-Saharan Africa.
AB - Neonatal pneumonia is a devastating condition. Most deaths in sub-Saharan Africa
can be attributed to preventable diseases, including pneumonia, diarrhoea and
malaria, which together killed an estimated 2.2 million children under the age of
5 years in 2012, accounting for a third of all under-five deaths in this region.
Some countries are making progress in reducing mortality through community-based
health schemes; however, most countries in this region are far from achieving the
World Health Organization Sustainable Development Goals for reducing childhood
morbidity and mortality. The microorganisms causing neonatal pneumonia are well
known. Both bacteria and viruses are commonly responsible, while fungal organisms
occur in the context of nosocomial disease, and parasites occur in HIV-infected
children. The common bacterial pathogens are group B streptococci (and other
streptococcal species) and Gram-negative organisms, most notably Escherichia coli
and Klebsiella spp. The viruses that predominate are the common respiratory
pathogens, namely respiratory syncytial virus, human rhinovirus, and influenza
virus. Viral disease is often nosocomial and transmitted to infected neonates in
the neonatal intensive care unit or other neonatal facilities by infected parents
and staff. Neonatal pneumonia often presents with non-specific respiratory
distress in newborns. In the premature infant it is often indistinguishable from
surfactant deficiency-associated respiratory distress syndrome. Therefore,
diagnostic testing that is cheap and reliable is urgently sought in this region.
All neonates with pneumonia must receive broad-spectrum antibiotic cover. This
usually entails the combination of penicillin and an aminoglycoside. A lack of
appropriate drugs and neonatal intensive care unit facilities are hampering
progress in managing neonatal pneumonia.
PMID- 28702284
TI - Respiratory infections and pneumonia: potential benefits of switching from
smoking to vaping.
AB - Abstaining from tobacco smoking is likely to lower the risk of respiratory
infections and pneumonia. Unfortunately, quitting smoking is not easy. Electronic
cigarettes (ECs) are emerging as an attractive long-term alternative nicotine
source to conventional cigarettes and are being adopted by smokers who wish to
reduce or quit cigarette consumption. Also, given that the propylene glycol in EC
aerosols is a potent bactericidal agent, switching from smoking to regular vaping
is likely to produce additional lung health benefits. Here, we critically address
some of the concerns arising from regular EC use in relation to lung health,
including respiratory infections and pneumonia. In conclusion, smokers who quit
by switching to regular ECs use can reduce risk and reverse harm from tobacco
smoking. Innovation in the e-vapour category is likely not only to further
minimise residual health risks, but also to maximise health benefits.
PMID- 28702285
TI - Comparison between diagnosis and treatment of community-acquired pneumonia in
children in various medical centres across Europe with the United States, United
Kingdom and the World Health Organization guidelines.
AB - BACKGROUND: The aim of this study was to review the current status and usage of
guidelines in the diagnosis and treatment of community-acquired pneumonia (CAP)
in European countries and to compare to established guidelines in the United
States (US), United Kingdom (UK), and the World Health Organization (WHO).
METHODS: A questionnaire was developed and distributed by the Community-Acquired
Pneumonia Paediatric Research Initiative (CAP-PRI) working group and distributed
to medical centres across Europe. RESULTS: Out of 19 European centres, 6 (31.6 %)
used WHO guidelines (3 in combination with other guidelines), 5 (26.3 %) used
national guidelines, and 5 (26.3 %) used local guidelines. Chest radiograph and
complete blood count were the most common diagnostic examinations, while
evaluation of clinical symptoms and laboratory tests varied significantly.
Tachypnoea and chest recession were considered criteria for diagnosis in all
three guidelines. In US and UK guidelines blood cultures, atypical bacterial and
viral detection tests were recommended. In European centres in outpatient
settings, amoxicillin was used in 16 (84 %) centers, clarithromycin in 9 (37 %)
centers and azithromycin in 7 (47 %) centers, whereas in hospital settings
antibiotic treatment varied widely. Amoxicillin is recommended as the first drug
of choice for outpatient treatment in all guidelines. CONCLUSIONS: Although local
variations in clinical criteria, laboratory tests, and antibiotic resistance
rates may necessitate some differences in standard empirical antibiotic regimens,
there is considerable scope for standardisation across European centres for the
diagnosis and treatment of CAP.
PMID- 28702286
TI - Antibiotics in childhood pneumonia: how long is long enough?
AB - Improved access to healthcare, vaccines and treatment with antibiotics has
reduced global mortality from childhood community-acquired pneumonia. However, as
respiratory viruses are responsible for most episodes of pneumonia, important
questions remain over who should receive these agents and the length of each
treatment course. Worldwide concerns with increasing antibiotic resistance in
respiratory pathogens and appeals for more prudent antibiotic prescribing provide
further urgency to these clinical questions. Unfortunately, guidelines for
treatment duration in particular are based upon limited (and often weak)
evidence, resulting in national and international guidelines recommending
treatment courses for uncomplicated pneumonia ranging from 3 to 10 days. The
advantages of short-course therapy include a lower risk of developing antibiotic
resistance, improved adherence, fewer adverse drug effects, and reduced costs.
The risks include treatment failure, leading to increased short- or long-term
morbidity, or even death. The initial challenge is how to distinguish between
bacterial and non-bacterial causes of pneumonia and then to undertake adequately
powered randomised-controlled trials of varying antibiotic treatment durations in
children who are most likely to have bacterial pneumonia. Meanwhile, healthcare
workers should recognise the limitations of current pneumonia treatment
guidelines and remember that antibiotic course duration is also determined by the
child's response to therapy.
PMID- 28702287
TI - Serum and exhaled breath condensate inflammatory cytokines in community-acquired
pneumonia: a prospective cohort study.
AB - BACKGROUND: The role and relationship between pro- and anti-inflammatory
cytokines represents one of the least studied aspects of the pathogenesis of
community-acquired pneumonia (CAP). The aim of the present study was to evaluate
pro- and anti-inflammatory cytokines at both local (lung) and systemic (blood)
levels and their relationship with the severity of the disease on admission and
time for a patient to reach clinical stability during hospitalisation. METHODS:
This was an observational, prospective, cohort study of hospitalised patients
with a diagnosis of CAP at the IRCCS Policlinico Hospital, Milan, Italy, between
April 2010 and January 2012. Ten pro-inflammatory cytokines (interleukin [IL]-1,
IL-1alpha, IL-1beta, IL-2, IL-6, IL-8, tumor necrosis factor [TNF]alpha and
interferon [IFN]gamma) and anti-inflammatory cytokines (IL-4 and IL-10) were
measured in both serum and exhaled breath condensate within 24 h after hospital
admission. RESULTS: A total of 74 patients (median age: 76 years; gender: 61 %
male) were enrolled. The anti- to pro-inflammatory cytokine ratio was reduced in
patients with severe disease on admission and prolonged time to reach clinical
stability. This was due to lower levels of anti-inflammatory cytokines in the
exhaled breath condensate and higher levels of pro-inflammatory cytokines in
serum. CONCLUSIONS: Dis-regulation between pro- and anti-inflammatory pathways
might be a part of the pathogenic mechanisms that lead to severe infection and
worse early clinical outcomes in CAP patients.
PMID- 28702288
TI - Burden of pneumococcal disease in adults aged 65 years and older: an Australian
perspective.
AB - BACKGROUND: The burden of pneumococcal disease in adults aged 65 years and older
in Australia is not well defined. This retrospective cross-sectional study
calculated rates for pneumococcal pneumonia using data from the Australian
Institute of Health and Welfare and from the Bettering Evaluation and Care of
Health program. METHODS: Invasive pneumococcal disease (IPD) incidence was
calculated using National Notifiable Diseases Surveillance System data.
Population estimates and pneumonia mortality data were from the Australian Bureau
of Statistics. Medical costs were derived from Australian Refined Diagnosis
Related Groups and the literature. Clinical and economic burden of pneumococcal
pneumonia hospitalisations and general practitioner (GP) visits were described
and compared with IPD. RESULTS: For adults aged >=65 years, pneumococcal
pneumonia hospitalisation incidence was 274 per 100,000 population in 2011-2012.
From 2004 to 2012, a mean of 2235 pneumonia hospitalisation deaths were recorded,
corresponding to a case fatality rate of 6.1 %. GP visits accounted for the
largest portion of healthcare encounters, with an annual average of 455
pneumococcal pneumonia GP visits per 100,000 population from 2008 to 2013. In
2012, IPD incidence was 19 per 100,000 population. The estimated annual costs of
treating pneumococcal pneumonia hospitalisations and GP visits were A$55,722,136
and A$1,604,189, respectively. Estimated costs for IPD were A$1,172,986.
CONCLUSIONS: The healthcare and economic burden of pneumococcal disease in adults
aged >=65 years in Australia is substantial, with the incidence of pneumococcal
pneumonia hospitalisation nearly 15-fold higher than for IPD. Despite this, it
remains less recognised than other infectious diseases such as influenza.
PMID- 28702289
TI - Macrolide resistance in pneumococci-is it relevant?
AB - Macrolide antibiotics are widely used for a range of indications, including
pneumonia. Both high-level and low-level resistance to macrolides is increasing
in pneumococci globally. Macrolide resistance in pneumococci is of limited
clinical relevance where beta-lactams remain the mainstay of treatment, such as
for moderate/severe pneumonia; however, data suggest that macrolides may not be
able to be relied on as monotherapy for serious pneumococcal infections.
PMID- 28702290
TI - Prevalence, pathogenesis, therapy, and prevention of cardiovascular events in
patients with community-acquired pneumonia.
AB - It is now well recognised that cardiac events occur relatively commonly in
patients with acute community-acquired pneumonia. While these events are more
frequent in patients with underlying risk factors-such as those with underlying
chronic cardiovascular and respiratory comorbidities, the elderly, and in nursing
home residents-they also occur in patients with no underlying risks other than
severe pneumonia. Recent research elucidating the underlying pathogenic
mechanisms related to these cardiac events has indicated a probable role for
platelet activation, which is possibly exacerbated by pneumolysin in the case of
pneumococcal infections. This, in turn, has resulted in the identification of
possible therapeutic strategies targeting platelet activation, as well as the
cardio-toxic activity of pneumolysin. These issues represent the primary focus of
the current review.
PMID- 28702291
TI - A longitudinal study of natural antibody development to pneumococcal surface
protein A families 1 and 2 in Papua New Guinean Highland children: a cohort
study.
AB - BACKGROUND: Pneumococcal surface protein A (PspA), a conserved virulence factor
essential for Streptococcus pneumoniae attachment to upper respiratory tract
(URT) epithelia, is a potential vaccine candidate for preventing colonisation.
METHODS: This cohort study was conducted in the Asaro Valley in the Eastern
Highlands Province of Papua New Guinea, of which Goroka town is the provincial
capital. The children included in the analysis were participants in a neonatal
pneumococcal conjugate vaccine trial (ClinicalTrials.gov NCT00219401) that was
conducted between 2005 and 2009. We investigated the development of anti-PspA
antibodies in the first 18 months of life relative to URT pneumococcal carriage
in Papua New Guinean infants who experience one of the earliest and highest
colonisation rates in the world. Blood samples and nasopharyngeal swabs were
collected from a cohort of 88 children at ages 3, 9, and 18 months to quantify
immunoglobulin G (IgG) levels to PspA families 1 and 2 using an enzyme-linked
immunosorbent assay and to determine URT carriage. RESULTS: Seventy-three per
cent (64/88) of infants carried S. pneumoniae at age 3 months; 85 % (75/88) at 9
months, and 83 % (73/88) at 18 months. PspA-IgG levels declined between ages 3
and 9 months (p < 0.001), then increased between 9 and 18 months (p < 0.001). At
age 3 months, pneumococcal carriers showed lower PspA1-IgG levels (geometric mean
concentration [GMC] 602 arbitrary units [AU]/ml, 95 % confidence interval [CI]
497-728) than non-carriers (GMC 1058 AU/ml [95 % CI 732-1530]; p = 0.008), while
at 9 months, PspA1- and PspA2-IgG levels were significantly higher in carriers
(PspA1: 186 AU/ml, 95 % CI 136-256; PspA2: 284 AU/ml, 95 % CI 192-421) than in
non-carriers (PspA1 87 AU/ml, 95 % CI 45-169; PspA2 74 AU/ml, 95 % CI 34-159)
(PspA1: p = 0.037, PspA2: p = 0.003). CONCLUSION: Our findings confirm that PspA
is immunogenic and indicate that natural anti-PspA immune responses are acquired
through exposure and develop with age. PspA may be a useful candidate in an
infant pneumococcal vaccine to prevent early URT colonisation.
PMID- 28702292
TI - Geographic consistency in dominant, non-typeable Haemophilus influenzae genotypes
colonising four distinct Australian paediatric groups: a cohort study.
AB - Non-typeable Haemophilus influenzae (NTHi)-associated ear and respiratory
diseases (including pneumonia) represent a major health burden in many parts of
the world. NTHi strains retrieved from the upper airways commonly reflect those
found in the lower airways. Despite growing genomic and genotyping data on NTHi,
there remains a limited understanding of global and regional NTHi population
structures. The aim of this study was to determine whether nasopharyngeal
carriage in four Australian paediatric groups at varying risk of NTHi
colonisation was dominated by the same NTHi genotypes. Genotyping data generated
by PCR-ribotyping were evaluated for 3070 NTHi isolates colonising the
nasopharynges of Aboriginal and non-Aboriginal children enrolled in four
longitudinal studies in three separate urban and remote regions of Australia.
Several NTHi PCR-ribotypes dominated in nasopharyngeal carriage, irrespective of
study setting. Principal coordinates analysis confirmed a cluster of common PCR
ribotypes among all cohorts. In conclusion, we identified dominant PCR-ribotypes
common to geographically disparate Australian paediatric populations. Future
genomic analyses will shed further light on the precise factors underlying the
dominance of certain NTHi strains in nasopharyngeal carriage.
PMID- 28702293
TI - The definition and classification of pneumonia.
AB - Following the publication of a volume of Pneumonia focused on diagnosis, the
journal's Editorial Board members debated the definition and classification of
pneumonia and came to a consensus on the need to revise both of these. The
problem with our current approach to the classification of pneumonia is twofold:
(i) it results in widespread empirical, and often unnecessary, use of
antimicrobials that contributes to pathogen resistance; and (ii) it contributes
to heterogeneity among the groups of subjects compared in research, causing
misclassification bias and mixtures of effects that threaten internal validity.
After outlining the problem of classification, this commentary describes the
strengths and weaknesses of a range of systems for the classification of
pneumonia. The commentary then calls for debate to generate consensus
classifications in the field, proposing a working definition and way forward
focusing on the following three points: (i) pneumonia should be defined as an
acute infection of the lung parenchyma by various pathogens, excluding the
condition of bronchiolitis; (ii) defining pneumonia as a group of specific
(co)infections with different characteristics is an ideal that currently has
limited use, because the identification of aetiologic organisms in individuals is
often not possible (however, the benefits of classifying pneumonia into specific,
more homogenous phenotypes should be carefully considered when designing research
studies); and (iii) investigation of more homogenous pneumonia groupings is
achievable and is likely to yield more rapid advances in the field.
PMID- 28702294
TI - Aboriginal and non-Aboriginal children in Western Australia carry different
serotypes of pneumococci with different antimicrobial susceptibility profiles.
AB - BACKGROUND: Carriage of Streptococcus pneumoniae is considered a precursor to
pneumococcal diseases including pneumonia. As part of the Kalgoorlie Otitis Media
Research Project, we characterised pneumococci isolated from the nasopharynx of
Western Australian Aboriginal and non-Aboriginal children. METHODS: Between 1999
and 2005, 100 Aboriginal and 180 non-Aboriginal children were followed from birth
to two years, with nasopharyngeal aspirates collected at ages 1-3 and 6-8 weeks,
then at 4, 6, 12, 18 and 24 months. Introduction of 7-valent pneumococcal
conjugate vaccine (7vPCV) in 2001 enabled evaluation of its impact on carriage in
study participants according to vaccines doses received. Pneumococcal serotyping
was performed by Quellung and antimicrobial susceptibility by disk diffusion and
Etest(r). Molecular epidemiology of pneumococcal isolates was investigated by
pulse-field gel electrophoresis and multilocus sequence typing. RESULTS: Overall,
the prevalence of 7vPCV serotypes was similar for Aboriginal and non-Aboriginal
children (19 % vs. 16 %), but the prevalence of non-vaccine serotypes was higher
in Aboriginal children (22 % vs. 7 %). A multi-resistant 6B clone (ST90) was
found only in non-Aboriginal children. Aboriginal children who received three
doses of 7vPCV had lower odds of carrying 7vPCV serotypes (odds ratio [OR] 0.19,
95 % CI 0.08-0.44) and higher odds of carrying non-vaccine serotypes (OR 2.37, 95
% CI 1.13-4.99) than unvaccinated Aboriginal children; this finding was not
observed in non-Aboriginal children. CONCLUSIONS: This unique study shows
important differences in pneumococcal serotypes, genotypes, and antimicrobial
susceptibility between Aboriginal and non-Aboriginal children living in the same
geographic area before widespread 7vPCV use, and highlights the need for ongoing
post-vaccination surveillance in outback Australia.
PMID- 28702295
TI - Carrier priming to improve pneumococcal disease control and reduce the
international program's cost in children.
AB - Pneumococcal conjugate vaccine (PCV) has the potential to interact with other
vaccines containing diphtheria toxin-like antigens (such as those found in the
DTP vaccine) upon sequential administration. This is attributed to the similarity
of the diphtheria toxoid antigen to the carrier protein used to make PCV, (known
as cross reactive material [CRM]) to diphtheria toxin 197 or CRM197. The
interaction could lead to enhanced immunogenicity of PCV as a result of a
phenomenon called carrier priming, whereby DTP is given some weeks before the
first dose of PCV. This phenomenon could be implemented in the immunisation
schedule in developing countries and among vulnerable populations to enhance the
immunogenicity of PCV, reduce the number of doses required, and produce a more
cost-effective immunisation program in developing countries.
PMID- 28702296
TI - How and when to use common biomarkers in community-acquired pneumonia.
AB - Community-acquired pneumonia (CAP) is a leading cause of death in both the
developed and developing world. The very young and elderly are especially
vulnerable. Even with appropriate early antibiotics we still have not improved
the outcomes in these patients since the 1950s, with 30-day case fatality rates
of between 10-12%. Interventions to improve outcomes include immunomodulatory
agents such as macrolides and corticosteroids. Treating doctors identify CAP
patients who are likely to have poor outcomes by using severity scores such as
the pneumonia severity index and CURB-65, which allows these patients to be
placed in ICU settings from the start of the admission. Another novel way to
identify these patients is with the use of biomarkers. This review illustrates
how various biomarkers have been shown to predict mortality, complications and
response to treatment in CAP patients. The evidence using either procalcitonin or
C-reactive protein to demonstrate response to treatment and hence that the
antibiotics chosen are appropriate can play an important role in antibiotic
stewardship.
PMID- 28702297
TI - Novel vaccination approaches to prevent tuberculosis in children.
AB - Pediatric tuberculosis (TB) is an underappreciated problem and accounts for 10 %
of all TB deaths worldwide. Children are highly susceptible to infection with
Mycobacterium tuberculosis and interrupting TB spread would require the
development of effective strategies to control TB transmission in pediatric
populations. The current vaccine for TB, M. bovis Bacille Calmette-Guerin (BCG),
can afford some level of protection against TB meningitis and severe forms of
disseminated TB in children; however, its efficacy against pulmonary TB is
variable and the vaccine does not afford life-long protective immunity. For these
reasons there is considerable interest in the development of new vaccines to
control TB in children. Multiple vaccine strategies are being assessed and
include recombinant forms of the existing BCG vaccine, protein or viral
candidates designed to boost BCG-induced immunity, or live attenuated forms of M.
tuberculosis. A number of these candidates have entered clinical trials; however,
no vaccine has shown improved protective efficacy compared to BCG in humans. The
current challenge is to identify the most suitable candidates to progress from
early to late stage clinical trials, in order to deliver a vaccine that can
control and hopefully eliminate the global threat of TB.
PMID- 28702298
TI - Tuberculosis and pneumonia in HIV-infected children: an overview.
AB - Pneumonia remains the most common cause of hospitalization and the most important
cause of death in young children. In high human immunodeficiency virus (HIV)
burden settings, HIV-infected children carry a high burden of lower respiratory
tract infection from common respiratory viruses, bacteria and Mycobacterium
tuberculosis. In addition, Pneumocystis jirovecii and cytomegalovirus are
important opportunistic pathogens. As the vertical transmission risk of HIV
decreases and access to antiretroviral therapy increases, the epidemiology of
these infections is changing, but HIV-infected infants and children still carry a
disproportionate burden of these infections. There is also increasing recognition
of the impact of in utero exposure to HIV on the general health of exposed but
uninfected infants. The reasons for this increased risk are not limited to
socioeconomic status or adverse environmental conditions-there is emerging
evidence that these HIV-exposed but uninfected infants may have particular immune
deficits that could increase their vulnerability to respiratory pathogens. We
discuss the impact of tuberculosis and other lower respiratory tract infections
on the health of HIV-infected infants and children.
PMID- 28702299
TI - Drug-resistant tuberculosis and advances in the treatment of childhood
tuberculosis.
AB - Over the last 10 years, interest in pediatric tuberculosis (TB) has increased
dramatically, together with increased funding and research. We have a better
understanding of the burden of childhood TB as well as a better idea of how to
diagnose it. Our appreciation of pathophysiology is improved and with it
investigators are beginning to consider pediatric TB as a heterogeneous entity,
with different types and severity of disease being treated in different ways.
There have been advances in how to treat both TB infection and TB disease caused
by both drug-susceptible as well as drug-resistant organisms. Two completely
novel drugs, bedaquiline and delamanid, have been developed, in addition to the
use of older drugs that have been re-purposed. New regimens are being evaluated
that have the potential to shorten treatment. Many of these drugs and regimens
have first been investigated in adults with children an afterthought, but
increasingly children are being considered at the outset and, in some instances
studies are only conducted in children where pediatric-specific issues exist.
PMID- 28702300
TI - Non-adherence to community oral-antibiotic treatment in children with fast
breathing pneumonia in Malawi- secondary analysis of a prospective cohort study.
AB - BACKGROUND: Despite significant progress, pneumonia is still the leading cause of
infectious deaths in children under five years of age. Poor adherence to
antibiotics has been associated with treatment failure in World Health
Organisation (WHO) defined clinical pneumonia; therefore, improving adherence
could improve outcomes in children with fast-breathing pneumonia. We examined
clinical factors that may affect adherence to oral antibiotics in children in the
community setting in Malawi. METHODS: We conducted a sub-analysis of a
prospective cohort of children aged 2-59 months diagnosed by community health
workers (CHW) in rural Malawi with WHO fast-breathing pneumonia. Clinical factors
identified during CHW diagnosis were investigated using multivariate logistic
regression for association with non-adherence, including concurrent diagnoses and
treatments. Adherence was measured at both 80% and 100% completion of prescribed
oral antibiotics. RESULTS: Eight hundred thirty-four children were included in
our analysis, of which 9.5% and 20.0% were non-adherent at 80% and 100% of
treatment completion, respectively. A concurrent infectious diagnosis (OR: 1.76,
95% CI: 0.84-2.96/OR: 1.81, 95% CI: 1.21-2.71) and an illness duration of >24 h
prior to diagnosis (OR: 2.14, 95% CI: 1.27-3.60/OR: 1.88, 95% CI: 1.29-2.73) had
higher odds of non-adherence when measured at both 80% and 100%. Older age was
associated with lower odds of non-adherence when measured at 80% (OR: 0.41, 95%
CI: 0.21-0.78). CONCLUSION: Non-adherence to oral antibiotics was not uncommon in
this rural sub-Saharan African setting. As multiple diagnoses by the CHW and
longer illness were important factors, this provides an opportunity for further
investigation into targeted interventions and refinement of referral guidelines
at the community level. Further research into the behavioural drivers of non
adherence within this setting is needed.
PMID- 28702301
TI - Childhood tuberculosis-out of the shadows.
PMID- 28702302
TI - Tuberculosis exposure, infection and disease in children: a systematic diagnostic
approach.
AB - The accurate diagnosis of tuberculosis (TB) in children remains challenging. A
myriad of common childhood diseases can present with similar symptoms and signs,
and differentiating between exposure and infection, as well as infection and
disease can be problematic. The paucibacillary nature of childhood TB complicates
bacteriological confirmation and specimen collection is difficult. In most
instances intrathoracic TB remains a clinical diagnosis. TB infection and disease
represent a dynamic continuum from TB exposure with/without infection, to
subclinical/incipient disease, to non-severe and severe disease. The clinical
spectrum of intrathoracic TB in children is broad, and the classification of
clinical, radiological, endoscopic, and laboratory findings into recognized
clinical syndromes allows a more refined diagnostic approach in order to minimize
both under- and over-diagnosis. Bacteriological confirmation can be improved
significantly by collecting multiple, high-quality specimens from the most
appropriate source. Mycobacterial testing should include traditional smear
microscopy and culture, as well as nucleic acid amplification testing. A
systematic approach to the child with recent exposure to TB, or with clinical and
radiological findings compatible with this diagnosis, should allow pragmatic
classification as TB exposure, infection, or disease to facilitate timely and
appropriate management. It is important to also assess risk factors for TB
disease progression and to undertake follow-up evaluations to monitor treatment
response and ongoing evidence supporting a TB, or alternative, diagnosis.
PMID- 28702303
TI - Pulmonary infections in the returned traveller.
AB - Pulmonary infections in the returned traveller are a common presentation. A wide
variety of infections may present with pulmonary symptoms. It is important for
clinicians to differentiate the cause of these symptoms. The risk of contracting
certain travel-related pulmonary diseases depends on travel destination, length
of stay, activities undertaken and co-morbidities. Some pathogens are found
worldwide, whilst others are related to specific locations. This review article
will discuss the approach to diagnosing and treating pulmonary infections in the
returned traveller.
PMID- 28702304
TI - Oral versus intravenous clarithromycin in moderate to severe community-acquired
pneumonia: an observational study.
AB - OBJECTIVES: British Thoracic Society guidelines recommend clarithromycin in
addition to beta-lactam antibiotics for patients with community-acquired
pneumonia and CURB-65 score 2-5. Intravenous therapy is commonly used but there
are few data on whether oral therapy is equally effective. METHODS: This
observational study used propensity matching to compare two groups of patients
with moderate to severe community-acquired pneumonia (CURB-65 score 2-5) treated
with oral (n = 226) or intravenous (n = 226) clarithromycin on admission.
Outcomes were 30-day mortality, intensive care unit admission, time to clinical
stability, and length of hospital stay. RESULTS: There was no significant
difference in 30-day mortality (16.8% for intravenous [IV] group vs. 14.6% for
oral group, hazard ratio for IV group 1.11 95% CI 0.70-1.78), ICU admission
(10.6% in both groups) or complications (10.6% for IV group and 9.3% for oral
group) between the groups. The time to clinical stability in both cohorts was a
median of 5 days (interquartile range 3-7 days, p = 0.3). The median length of
hospital stay was 8 days in the IV group (interquartile range 4-14 days) and 7
days in the oral group (interquartile range 4-13 days), p = 0.5. No other
differences were observed between oral and IV groups. CONCLUSION: Where the oral
route is not compromised, oral macrolides appear to be equivalent to IV in
treating moderate to severe CAP.
PMID- 28702305
TI - Increased risk of pneumonia in residents living near poultry farms: does the
upper respiratory tract microbiota play a role?
AB - BACKGROUND: Air pollution has been shown to increase the susceptibility to
community-acquired pneumonia (CAP). Previously, we observed an increased
incidence of CAP in adults living within 1 km from poultry farms, potentially
related to particulate matter and endotoxin emissions. We aim to confirm the
increased risk of CAP near poultry farms by refined spatial analyses, and we
hypothesize that the oropharyngeal microbiota composition in CAP patients may be
associated with residential proximity to poultry farms. METHODS: A spatial kernel
model was used to analyze the association between proximity to poultry farms and
CAP diagnosis, obtained from electronic medical records of 92,548 GP patients.
The oropharyngeal microbiota composition was determined in 126 hospitalized CAP
patients using 16S-rRNA-based sequencing, and analyzed in relation to residential
proximity to poultry farms. RESULTS: Kernel analysis confirmed a significantly
increased risk of CAP when living near poultry farms, suggesting an excess risk
up to 1.15 km, followed by a sharp decline. Overall, the oropharyngeal microbiota
composition differed borderline significantly between patients living <1 km and
>=1 km from poultry farms (PERMANOVA p = 0.075). Results suggested a higher
abundance of Streptococcus pneumoniae (mean relative abundance 34.9% vs. 22.5%, p
= 0.058) in patients living near poultry farms, which was verified by
unsupervised clustering analysis, showing overrepresentation of a S. pneumoniae
cluster near poultry farms (p = 0.049). CONCLUSION: Living near poultry farms is
associated with an 11% increased risk of CAP, possibly resulting from changes in
the upper respiratory tract microbiota composition in susceptible individuals.
The abundance of S. pneumoniae near farms needs to be replicated in larger,
independent studies.
PMID- 28702306
TI - Impact of viral multiplex real-time PCR on management of respiratory tract
infection: a retrospective cohort study.
AB - BACKGROUND: Significance and clinical utility of multiple virus detection by
multiplex real-time polymerase chain reaction (rtPCR) in respiratory tract
infection remain unclear. METHODS: This retrospective cohort study analyzed how
virus detection affected clinical management. During a 27-month period, clinical
and laboratory information was collected from all children and adults in two
Swiss tertiary centres whose respiratory samples were tested for respiratory
viruses with a 16-plex rtPCR test. RESULTS: Pathogens were identified in 140 of
254 patients (55%); of those patients, there was >=1 virus in 91 (65%), >= 1
bacterium in 53 (38%), and >=1 virus and bacterium in 11 (8%). Of 80 patients
with viral infection, 59 (74%) received antibiotics. Virus detection was
associated with discontinuation of antibiotics in 2 of 20 adults (10%) and 6 of
14 children (43%). Overall 12 adults (34%) and 18 children (67%) were managed
correctly without antibiotics after virus detection (p = 0.01). When taking
biomarkers, radiologic presentations, and antibiotic pre-treatment into account,
the impact of rtPCR and appropriateness of therapy for clinically viral
infections increased to 100% in children and 62% in adults. CONCLUSIONS: A
substantial reduction of unnecessary antibiotic prescriptions seems possible.
Appropriate application of rtPCR results in respiratory tract infections should
be encouraged.
PMID- 28702307
TI - Childhood pneumonia and meningitis in the Eastern Highlands Province, Papua New
Guinea in the era of conjugate vaccines: study methods and challenges.
AB - BACKGROUND: Pneumonia and meningitis are common causes of severe childhood
illness in Papua New Guinea (PNG). The etiology of both clinical conditions in
PNG has not been recently assessed. Changes in lifestyle, provision and access to
healthcare, antimicrobial utilization and resistance, and the national childhood
vaccination schedule necessitate reassessment. METHODS: A prospective case
control study was undertaken, enrolling children <5 years of age to determine the
contemporary etiology of clinically defined moderate or severe pneumonia or
suspected meningitis. Cases were identified following presentation for inpatient
or outpatient care in Goroka town, the major population centre in the Eastern
Highlands Province. Following enrolment, routine diagnostic specimens including
blood, nasopharyngeal swabs, urine and (if required) cerebrospinal fluid, were
obtained. Cases residing within one hour's drive of Goroka were followed up, and
recruitment of healthy contemporaneous controls was undertaken in the cases'
communities. RESULTS: 998 cases and 978 controls were enrolled over 3 years. This
included 784 cases (78.6%) with moderate pneumonia, 187 (18.7%) with severe
pneumonia and 75 (7.5%) with suspected meningitis, of whom 48 (4.8%) had
concurrent pneumonia. The median age of cases was 7.8 months (Interquartile range
[IQR] 3.9-14.3), significantly lower than community controls, which was 20.8
months (IQR 8.2-36.4). Half the cases were admitted to hospital (500/998; 50.1%).
Recruitment of cases and controls and successful collection of diagnostic
specimens improved throughout the study, with blood volume increasing and rates
of blood culture contamination decreasing. The overall case fatality rate was
18/998 (1.8%). Of cases eligible for follow-up, outcome data was available from
76.7%. Low but increasing coverage of Haemophilus influenzae type B conjugate
vaccines on the national schedule was observed during the study period: three
dose DTPw-HepB-Hib coverage in children >3 months increased from 14.9 to 43.0%
and 29.0 to 47.7% in cases and controls (both p < 0.001). Despite inclusion in
the national immunization program in 2014, 2015 PCV13 three-dose coverage in
cases and controls >3 months was only 4.0 and 6.5%. CONCLUSIONS: Recruitment of
large numbers of pediatric pneumonia and meningitis cases and community controls
in a third-world setting presents unique challenges. Successful enrolment of 998
cases and 978 controls with comprehensive clinical data, biological specimens and
follow up was achieved. Increased vaccine coverage remains an ongoing health
priority.
PMID- 28702308
TI - Pneumococcal conjugate vaccine implementation in middle-income countries.
AB - BACKGROUND: Since 2000, the widespread adoption of pneumococcal conjugate
vaccines (PCVs) has had a major impact in the prevention of pneumonia. Limited
access to international financial support means some middle-income countries
(MICs) are trailing in the widespread use of PCVs. We review the status of PCV
implementation, and discuss any needs and gaps related to low levels of PCV
implementation in MICs, with analysis of possible solutions to strengthen the PCV
implementation process in MICs. MAIN BODY: We searched PubMed, PubMed Central,
Ovid MEDLINE, and SCOPUS databases using search terms related to pneumococcal
immunization, governmental health policy or programmes, and MICs. Two authors
independently reviewed the full text of the references, which were assessed for
eligibility using pre-defined inclusion and exclusion criteria. The search terms
identified 1,165 articles and the full texts of 21 were assessed for suitability,
with eight articles included in the systematic review. MICs are implementing PCVs
at a slower rate than donor-funded low-income countries and wealthier developed
countries. A significant difference in the uptake of PCV in lower middle-income
countries (LMICs) (71%) and upper middle-income countries (UMICs) (48%) is
largely due to an unsuccessful process of "graduation" of MICs from GAVI
assistance, an issue that arises as countries cross the income eligibility
threshold and are no longer eligible to receive the same levels of financial
assistance. A lack of country-specific data on disease burden, a lack of local
expertise in economic evaluation, and the cost of PCV were identified as the
leading causes of the slow uptake of PCVs in MICs. Potential solutions mentioned
in the reviewed papers include the use of vaccine cost-effectiveness analysis and
the provision of economic evidence to strengthen decision-making, the evaluation
of the burden of disease, and post-introduction surveillance to monitor vaccine
impact. CONCLUSION: The global community needs to recognise the impediments to
vaccine introduction into MICs. Improving PCV access could help decrease the
incidence of pneumonia and reduce the selection pressure for pneumococcal
antimicrobial resistance.
PMID- 28702309
TI - Encouraging rational antibiotic use in childhood pneumonia: a focus on Vietnam
and the Western Pacific Region.
AB - Globally, pneumonia is considered to be the biggest killer of infants and young
children (aged <5 years) outside the neonatal period, with the greatest disease
burden in low- and middle-income countries. Optimal management of childhood
pneumonia is challenging in settings where clinicians have limited information
regarding the local pathogen and drug resistance profiles. This frequently
results in unnecessary and poorly targeted antibiotic use. Restricting antibiotic
use is a global priority, particularly in Asia and the Western Pacific Region
where excessive use is driving high rates of antimicrobial resistance. The
authors conducted a comprehensive literature review to explore the antibiotic
resistance profile of bacteria associated with pneumonia in the Western Pacific
Region, with a focus on Vietnam. Current management practices were also
considered, along with the diagnostic dilemmas faced by doctors and other factors
that increase unnecessary antibiotic use. This review offers some suggestions on
how these issues may be addressed.
PMID- 28702310
TI - Development of PCRSeqTyping-a novel molecular assay for typing of Streptococcus
pneumoniae.
AB - BACKGROUND: Precise serotyping of pneumococci is essential for vaccine
development, to better understand the pathogenicity and trends of drug
resistance. Currently used conventional and molecular methods of serotyping are
expensive and time-consuming, with limited coverage of serotypes. An accurate and
rapid serotyping method with complete coverage of serotypes is an urgent
necessity. This study describes the development and application of a novel
technology that addresses this need. METHODS: Polymerase chain reaction (PCR) was
performed, targeting 1061 bp cpsB region, and the amplicon was subjected to
sequencing. The sequence data was analyzed using the National Centre for
Biotechnology Information database. For homologous strains, a second round of
PCR, sequencing, and data analysis was performed targeting 10 group-specific
genes located in the capsular polysaccharide region. Ninety-one pneumococcal
reference strains were analyzed with PCRSeqTyping and compared with Quellung
reaction using Pneumotest Kit (SSI, Denmark). RESULTS: A 100% correlation of
PCRSeqTyping results was observed with Pneumotest results. Fifty-nine reference
strains were uniquely identified in the first step of PCRSeqTyping. The remaining
32 homologous strains out of 91 were also uniquely identified in the second step.
CONCLUSION: This study describes a PCRSeqTyping assay that is accurate and rapid,
with high reproducibility. This assay is amenable for clinical testing and does
not require culturing of the samples. It is a significant improvement over other
methods because it covers all pneumococcal serotypes, and it has the potential
for use in diagnostic laboratories and surveillance studies.
PMID- 28702311
TI - The evidence for non-typeable Haemophilus influenzae as a causative agent of
childhood pneumonia.
AB - Haemophilus influenzae type b (Hib) was a major cause of bacterial pneumonia in
children prior to the introduction of Hib-conjugate vaccines. The widespread use
of Hib-conjugate vaccines has resulted in a significant decline in the number of
cases of invasive Hib disease, including bacteraemic pneumonia, in areas where
the vaccine has been implemented. In many countries, non-typeable H. influenzae
(NTHI) is now the most common cause of invasive haemophilus infection in all
ages. NTHI are a recognized cause of bacteraemic and non-bacteraemic pneumonia in
children and in adults. Less than 10% of cases of pediatric pneumonia are
bacteraemic, and children generally do not expectorate lower respiratory tract
secretions, so determining the microbial cause of a non-bacteraemic pneumonia is
challenging. In this commentary the evidence that NTHI is a cause of pneumonia in
children is briefly reviewed.
PMID- 28702312
TI - Aloesin Suppresses Cell Growth and Metastasis in Ovarian Cancer SKOV3 Cells
through the Inhibition of the MAPK Signaling Pathway.
AB - Aloesin is an active constituent of the herb aloe vera and plays a crucial role
in anti-inflammatory activity, ultraviolet protection, and antibacterium. We
investigated the role and possible mechanisms of aloesin in the cell growth and
metastasis of ovarian cancer. It was found that aloesin inhibited cell viability
and cell clonality in a dose-dependent manner. It arrests the cell cycle at the S
phase and induced apoptosis in SKOV3 cells. In an in vivo experiment, it was
observed that aloesin inhibited tumor growth. Moreover, it inhibited migration
and invasion of cancer in SKOV3 cells. Interestingly, members from the mitogen
activated protein kinase (MAPK) signaling family became less phosphorylated as
the aloesin dose increased. This suggests that aloesin exerts its anticancer
effect through the MAPK signaling pathway. Our data also highlights the
possibility of using aloesin as a novel therapeutic drug for ovarian cancer
treatment.
PMID- 28702313
TI - Relationship between objectively measured intensity of physical activity and self
reported enjoyment of physical activity.
AB - Physical activity is an important factor for the maintenance of health. Enjoyment
of physical activity is essential to motivate persons to engage in sufficient
physical activity. We examined whether self-reported enjoyment of PA is
associated with objective measurement of the intensity of PA. A cardiovascular
examination program was provided for individuals aged 40-75 years without a
history of cardiovascular events in Greifswald, Germany between 2012 and 2013.
Participants (n = 255) were asked to wear a three-axial accelerometer device
(ActiGraph, GT3X +, Pensacola, Florida, USA) for 7 consecutive days. After
wearing the device, the participants were asked to complete the 18-item self
administered physical activity enjoyment scale (PACES). Participants' (n = 200)
daily minutes of moderate-to-vigorous physical activity (MVPA) and their
enjoyment of PA were analysed in a linear regression approach. The mean age of
the participants was 56.3 +/- 9.7 years, 41.0% were male. The average MVPA
duration was 44.4 +/- 27.3 min per day. In the regression analysis, enjoyment of
PA was positively associated with MVPA (beta = 0.18, 95% CI (0.05; 0.31), p =
0.009), participants with higher enjoyment of PA showed higher MVPA. We found a
positive association between MVPA and enjoyment of PA, although for male
participants only. Between bouted MVPA and enjoyment of PA there was no
significant relationship.
PMID- 28702314
TI - Development and testing of a community audit tool to assess rural built
environments: Inventories for Community Health Assessment in Rural Towns.
AB - Rural populations face unique challenges to physical activity that are largely
driven by environmental conditions. However, research on rural built environments
and physical activity is limited by a paucity of rural-specific environmental
assessment tools. The aim of this paper is to describe the development and
testing of a rural assessment tool: Inventories for Community Health Assessment
in Rural Towns (iCHART). The iCHART tool was developed in 2013 through a
multistep process consisting of an extensive literature search to identify
existing tools, an expert panel review, and pilot testing in five rural US
communities. Tool items represent rural built environment features that influence
active living and physical activity: community design, transportation
infrastructure, safety, aesthetics, and recreational facilities. To assess
reliability, field testing was performed in 26 rural communities across five
states between July and November of 2014. Reliability between the research team
and community testers was high among all testing communities (average percent
agreement = 77%). Agreement was also high for intra-rater reliability (average
kappa = 0.72) and inter-rater reliability (average percent agreement = 84%) among
community testers. Findings suggest that the iCHART tool provides a reliable
assessment of rural built environment features and can be used to inform the
development of contextually-appropriate physical activity opportunities in rural
communities.
PMID- 28702315
TI - Participation in a farmers' market fruit and vegetable prescription program at a
federally qualified health center improves hemoglobin A1C in low income
uncontrolled diabetics.
AB - Fruit and vegetable prescription programs have been shown to increase consumption
of fresh produce, but whether they have an impact on medical outcomes is unknown.
The purpose of this study was to examine the role of participation in a farmers'
market and fruit and vegetable prescription program on changes in hemoglobin A1C
(HbA1C), blood pressure (BP) and weight in patients with uncontrolled type 2
diabetes at a federally qualified health center (FQHC) in Detroit, MI. The 13
week Fresh Prescription program (June 2015-October 2015) was designed to improve
access and consumption of produce among low-income patients with uncontrolled
type 2 diabetes. The program allotted up to $40 ($10 per week for up to four
weeks) for purchase of produce from a FQHC located farmers' market. Adult, non
pregnant patients with a history of type 2 diabetes that had an elevated HbA1C >
6.5 within three months before Fresh Prescription program were eligible to
participate. HgA1c, BP and weight were collected within three months of program
start and within three months of completion. There were 65 eligible participants
with complete biometric data. A statistically significant (p = 0.001) decrease in
HbA1C was found (9.54% to 8.83%). However, weight (208.3 lbs. to 209.0 lbs.) and
BP (135.1/79.3 mm Hg to 135.8/77.6 mm Hg) did not change from pre- to post-study
(p > 0.05). Access to a fruit and vegetable prescription program over a 13-week
period led to decreased HbA1C concentrations in uncontrolled type 2 diabetic
patients living in an urban area of predominately-lower socioeconomic status.
PMID- 28702316
TI - Sporotrichosis in a liver transplant patient: A case report and literature
review.
AB - The liver transplant patient was admitted to the hospital with hyperemic,
granulomatous, ulcerated lesion in the anterior compartment of the right lower
limb with report of local trauma. The agent Sporothrix schenckii was isolated
from biopsy of the lesion and lymph nodes of the right lower limb. In this case,
the treatment was difficult because the patient has severe pulmonary hypertension
and took the following drugs: warfarin, sildenafil, and tacrolimus. These
medicines interact with the antifungal, which made it difficult.
PMID- 28702317
TI - Fungal keratitis caused by Metarhizium anisopliae complex.
AB - PURPOSE: To report a case of fungal keratitis caused by Metarhizium anisopliae
complex. METHODS: Case report. RESULTS: Our patient presented with a central
corneal infiltrate. Fungal culture yielded a Metarhizium species. She was started
on antifungal agents with no significant improvement. A therapeutic corneal
transplant was performed after perforation. At two years follow up, she was free
of infection. CONCLUSION: Metarhizium anisopliae is a very rare cause of
keratitis. Although previous reported cases showed clinical improvement with
antifungal agents, this case required surgical treatment to control the
infection.
PMID- 28702318
TI - Aspergillus nodules in chronic granulomatous disease attributable to Aspergillus
ochraceus.
AB - Aspergillus ochraceus is a rare pulmonary pathogen. A 39 year old male with COPD
and chronic granulomatous disease presented with severe breathlessness and
recurrent infections. CT scan demonstrated multiple pulmonary nodules diagnosed
as chronic pulmonary aspergillosis. The patient's sputum grew Aspergillus
ochraceus thrice over 6 months, alongside positive Aspergillus IgG and serum
galactomannan. Despite treatment with itraconazole, the patient continued to be
symptomatic. We present the first case associating A. ochraceus with chronic
pulmonary aspergillosis.
PMID- 28702319
TI - Grandpaternal-induced transgenerational dietary reprogramming of the unfolded
protein response in skeletal muscle.
AB - OBJECTIVE: Parental nutrition and lifestyle impact the metabolic phenotype of the
offspring. We have reported that grandpaternal chronic high-fat diet (HFD)
transgenerationally impairs glucose metabolism in subsequent generations. Here we
determined whether grandpaternal diet transgenerationally impacts the
transcriptome and lipidome in skeletal muscle. Our aim was to identify tissue
specific pathways involved in transgenerational inheritance of environmental
induced phenotypes. METHODS: F0 male Sprague-Dawley rats were fed a HFD or chow
for 12 weeks before breeding with chow-fed females to generate the F1 generation.
F2 offspring were generated by mating F1 males fed a chow diet with an
independent line of chow-fed females. F1 and F2 offspring were fed chow or HFD
for 12 weeks. Transcriptomic and LC-MS lipidomic analyses were performed in
extensor digitorum longus muscle from F2-females rats. Gene set enrichment
analysis (GSEA) was performed to determine pathways reprogrammed by grandpaternal
diet. RESULTS: GSEA revealed an enrichment of the unfolded protein response
pathway in skeletal muscle of grand-offspring from HFD-fed grandfathers compared
to grand-offspring of chow-fed males. Activation of the stress sensor
(ATF6alpha), may be a pivotal point whereby this pathway is activated.
Interestingly, skeletal muscle from F1-offspring was not affected in a similar
manner. No major changes were observed in the skeletal muscle lipidome profile
due to grandpaternal diet. CONCLUSIONS: Grandpaternal HFD-induced obesity
transgenerationally affected the skeletal muscle transcriptome. This finding
further highlights the impact of parental exposure to environmental factors on
offspring's development and health.
PMID- 28702320
TI - Parental obesity leads to metabolic changes in the F2 generation in Drosophila.
AB - OBJECTIVE: A significant portion of the heritable risk for complex metabolic
disorders cannot be attributed to classic Mendelian genetic factors. At least
some of this missing heritability is thought to be due to the epigenetic
influence of parental and grandparental metabolic state on offspring health.
Previous work suggests that this transgenerational phenomenon is evolutionarily
conserved in Drosophila. These studies, however, have all depended on dietary
paradigms to alter parental metabolic state, which can have inconsistent
heritable effects on the metabolism of offspring. METHODS: Here we use AKHR null
alleles to induce obesity in the parental generation and then score both
metabolic parameters and genome-wide transcriptional responses in AKHR
heterozygote F1 progeny and genetically wild-type F2 progeny. RESULTS:
Unexpectedly, we observe elevated glycogen levels and changes in gene expression
in AKHR heterozygotes due to haploinsufficiency at this locus. We also show that
genetic manipulation of parental metabolism using AKHR mutations results in
significant physiological changes in F2 wild-type offspring of the
grandpaternal/maternal lineage. CONCLUSIONS: Our results demonstrate that genetic
manipulation of parental metabolism in Drosophila can have an effect on the
health of F2 progeny, providing a non-dietary paradigm to better understand the
mechanisms behind the transgenerational inheritance of metabolic state.
PMID- 28702321
TI - A high-content small molecule screen identifies novel inducers of definitive
endoderm.
AB - OBJECTIVES: Human embryonic stem cells (hESCs) and human induced pluripotent stem
cells (hiPSCs) can generate any given cell type in the human body. One challenge
for cell-replacement therapy is the efficient differentiation and expansion of
large quantities of progenitor cells from pluripotent stem cells produced under
good manufacturing practice (GMP). FOXA2 and SOX17 double positive definitive
endoderm (DE) progenitor cells can give rise to all endoderm-derived cell types
in the thymus, thyroid, lung, pancreas, liver, and gastrointestinal tract. FOXA2
is a pioneer transcription factor in DE differentiation that is also expressed
and functionally required during pancreas development and islet cell homeostasis.
Current differentiation protocols can successfully generate endoderm; however,
generation of mature glucose-sensitive and insulin-secreting beta-cells is still
a challenge. As a result, it is of utmost importance to screen for small
molecules that can improve DE and islet cell differentiation for cell-replacement
therapy for diabetic patients. METHODS: The aim of this study was to identify and
validate small molecules that can induce DE differentiation and further enhance
pancreatic progenitor differentiation. Therefore, we developed a large scale,
high-content screen for testing a chemical library of 23,406 small molecules to
identify compounds that induce FoxA2 in mouse embryonic stem cells (mESCs).
RESULTS: Based on our high-content screen algorithm, we selected 84 compounds
that directed differentiation of mESCs towards the FoxA2 lineage. Strikingly, we
identified ROCK inhibition (ROCKi) as a novel mechanism of endoderm induction in
mESCs and hESCs. DE induced by the ROCK inhibitor Fasudil efficiently gives rise
to PDX1+ pancreatic progenitors from hESCs. CONCLUSION: Taken together, DE
induction by ROCKi can simplify and improve current endoderm and pancreatic
differentiation protocols towards a GMP-grade cell product for beta-cell
replacement.
PMID- 28702322
TI - Mitochondrial transcription factor B2 is essential for mitochondrial and cellular
function in pancreatic beta-cells.
AB - OBJECTIVE: Insulin release from pancreatic beta-cells is controlled by plasma
glucose levels via mitochondrial fuel metabolism. Therefore, insulin secretion is
critically dependent on mitochondrial DNA (mtDNA) and the genes it encodes.
Mitochondrial transcription factor B2 (TFB2M) controls transcription of
mitochondrial-encoded genes. However, its precise role in mitochondrial
metabolism in pancreatic beta-cells and, consequently, in insulin secretion
remains unknown. METHODS: To elucidate the role of TFB2M in mitochondrial
function and insulin secretion in vitro and in vivo, mice with a beta-cell
specific homozygous or heterozygous knockout of Tfb2m and rat clonal insulin
producing cells in which the gene was silenced were examined with an array of
metabolic and functional assays. RESULTS: There was an effect of gene dosage on
Tfb2m expression and function. Loss of Tfb2m led to diabetes due to disrupted
transcription of mitochondrial DNA (mtDNA) and reduced mtDNA content. The ensuing
mitochondrial dysfunction activated compensatory mechanisms aiming to limit
cellular dysfunction and damage of beta-cells. These processes included the
mitochondrial unfolded protein response, mitophagy, and autophagy. Ultimately,
however, these cell-protective systems were overridden, leading to mitochondrial
dysfunction and activation of mitochondrial-dependent apoptotic pathways. In this
way, beta-cell function and mass were reduced. Together, these perturbations
resulted in impaired insulin secretion, progressive hyperglycemia, and,
ultimately, development of diabetes. CONCLUSIONS: Loss of Tfb2m in pancreatic
beta-cells results in progressive mitochondrial dysfunction. Consequently,
insulin secretion in response to metabolic stimuli is impaired and beta-cell mass
reduced. Our findings indicate that TFB2M plays an important functional role in
pancreatic beta-cells. Perturbations of its actions may lead to loss of
functional beta-cell mass, a hallmark of T2D.
PMID- 28702323
TI - AAV-mediated pancreatic overexpression of Igf1 counteracts progression to
autoimmune diabetes in mice.
AB - OBJECTIVE: Type 1 diabetes is characterized by autoimmune destruction of beta
cells leading to severe insulin deficiency. Although many improvements have been
made in recent years, exogenous insulin therapy is still imperfect; new
therapeutic approaches, focusing on preserving/expanding beta-cell mass and/or
blocking the autoimmune process that destroys islets, should be developed. The
main objective of this work was to test in non-obese diabetic (NOD) mice, which
spontaneously develop autoimmune diabetes, the effects of local expression of
Insulin-like growth factor 1 (IGF1), a potent mitogenic and pro-survival factor
for beta-cells with immunomodulatory properties. METHODS: Transgenic NOD mice
overexpressing IGF1 specifically in beta-cells (NOD-IGF1) were generated and
phenotyped. In addition, miRT-containing, IGF1-encoding adeno-associated viruses
(AAV) of serotype 8 (AAV8-IGF1-dmiRT) were produced and administered to 4- or 11
week-old non-transgenic NOD females through intraductal delivery. Several
histological, immunological, and metabolic parameters were measured to monitor
disease over a period of 28-30 weeks. RESULTS: In transgenic mice, local IGF1
expression led to long-term suppression of diabetes onset and robust protection
of beta-cell mass from the autoimmune insult. AAV-mediated pancreatic-specific
overexpression of IGF1 in adult animals also dramatically reduced diabetes
incidence, both when vectors were delivered before pathology onset or once
insulitis was established. Transgenic NOD-IGF1 and AAV8-IGF1-dmiRT-treated NOD
animals had much less islet infiltration than controls, preserved beta-cell mass,
and normal insulinemia. Transgenic and AAV-treated islets showed less expression
of antigen-presenting molecules, inflammatory cytokines, and chemokines important
for tissue-specific homing of effector T cells, suggesting IGF1 modulated islet
autoimmunity in NOD mice. CONCLUSIONS: Local expression of Igf1 by AAV-mediated
gene transfer counteracts progression to diabetes in NOD mice. This study
suggests a therapeutic strategy for autoimmune diabetes in humans.
PMID- 28702324
TI - The endogenous preproglucagon system is not essential for gut growth homeostasis
in mice.
AB - OBJECTIVE: The prevalence of obesity and related co-morbidities is reaching
pandemic proportions. Today, the most effective obesity treatments are glucagon
like peptide 1 (GLP-1) analogs and bariatric surgery. Interestingly, both
intervention paradigms have been associated with adaptive growth responses in the
gut; however, intestinotrophic mechanisms associated with or secondary to medical
or surgical obesity therapies are poorly understood. Therefore, the objective of
this study was to assess the local basal endogenous and pharmacological
intestinotrophic effects of glucagon-like peptides and bariatric surgery in mice.
METHODS: We used in situ hybridization to provide a detailed and comparative
anatomical map of the local distribution of GLP-1 receptor (Glp1r), GLP-2
receptor (Glp2r), and preproglucagon (Gcg) mRNA expression throughout the mouse
gastrointestinal tract. Gut development in GLP-1R-, GLP-2R-, or GCG-deficient
mice was compared to their corresponding wild-type controls, and intestinotrophic
effects of GLP-1 and GLP-2 analogs were assessed in wild-type mice. Lastly, gut
volume was determined in a mouse model of vertical sleeve gastrectomy (VSG).
RESULTS: Comparison of Glp1r, Glp2r, and Gcg mRNA expression indicated a
widespread, but distinct, distribution of these three transcripts throughout all
compartments of the mouse gastrointestinal tract. While mice null for Glp1r or
Gcg showed normal intestinal morphology, Glp2r-/- mice exhibited a slight
reduction in small intestinal mucosa volume. Pharmacological treatment with GLP-1
and GLP-2 analogs significantly increased gut volume. In contrast, VSG surgery
had no effect on intestinal morphology. CONCLUSION: The present study indicates
that the endogenous preproglucagon system, exemplified by the entire GCG gene and
the receptors for GLP-1 and GLP-2, does not play a major role in normal gut
development in the mouse. Furthermore, elevation in local intestinal and
circulating levels of GLP-1 and GLP-2 achieved after VSG has limited impact on
intestinal morphometry. Hence, although exogenous treatment with GLP-1 and GLP-2
analogs enhances gut growth, the contributions of endogenously-secreted GLP-1 and
GLP-2 to gut growth may be more modest and highly context-dependent.
PMID- 28702325
TI - The human digestive tract has proteases capable of gluten hydrolysis.
AB - OBJECTIVE: To identify, purify, and characterize the proteins responsible for
glutenase activity in the feces of healthy subjects and patients with celiac
disease (CD). METHODS: Sixteen subjects were included in this study; 8 were
healthy with no known food intolerances, and 8 were treated CD patients on a
gluten-free diet. Fecal samples were homogenized, and precipitated proteins were
purified by chromatography. Glutenase activity was evaluated by bioassays,
zymography, and high-performance liquid chromatography with immunogenic 33-mer,
19-mer, and 13-mer gliadin peptides. RESULTS: The gastrointestinal elastase 3B
(CEL3B), elastase 2A (CEL2A), and carboxypeptidase A1 (CBPA1) enzymes degraded
human gluten. These proteins fully hydrolyzed 13-mer and 19-mer gliadin peptides
that trigger immune-mediated enteropathy in individuals genetically predisposed
to CD and partially digested a 33-mer. Feces from patients with CD showed more
glutenase activity than feces from individuals without CD (171-466% higher).
Peptidase activity against the gliadin peptides also increased in patients with
CD. CONCLUSION: The digestive tracts of patients with CD and healthy subjects
have enzymatic machinery needed for gluten degradation. Patients with CD showed
more gluten hydrolysis than did healthy individuals, although, in both cases, a
fraction of 33-mer peptide remained intact. Gliadin peptides derived from
gastrointestinal digestion, especially the 33-mer, can potentially be used by
commensal microbiota from both CD-positive and CD-negative individuals, and
differences in bacterial hydrolysis can modify its immunogenic capacity.
PMID- 28702326
TI - Rev-Erb co-regulates muscle regeneration via tethered interaction with the NF-Y
cistrome.
AB - OBJECTIVE: The loss of skeletal muscle mass and strength are a central feature of
traumatic injury and degenerative myopathies. Unfortunately, pharmacological
interventions typically fail to stem the long-term decline in quality of life.
Reduced Rev-Erb-mediated gene suppression in cultured C2C12 myoblasts has been
shown to stimulate myoblast differentiation. Yet the mechanisms that allow Rev
Erb to pleiotropically inhibit muscle differentiation are not well understood. In
this study, we sought to elucidate the role of Rev-Erb in the regulation of
muscle differentiation and regeneration in vivo. METHODS: Using Rev-Erbalpha/beta
shRNAs, pharmacological ligands, and Rev-Erbalpha null and heterozygous mice, we
probed the mechanism of Rev-Erbalpha/beta regulation of muscle differentiation
and muscle regeneration. RESULTS: ChIP seq analysis of Rev-Erb in differentiating
myoblasts showed that Rev-Erbalpha did not transcriptionally regulate muscle
differentiation through cognate Rev-Erb/ROR-response elements but through
possible interaction with the cell fate regulator NF-Y at CCAAT-motifs. Muscle
differentiation is stimulated by Rev-Erb release from CCAAT-motifs at promoter
and enhancer elements of a number of myogenesis proteins. Partial loss of Rev-Erb
expression in mice heterozygous for Rev-Erbalpha accelerated muscle repair in
vivo whereas Rev-Erb knockout mice showed deficiencies in regenerative repair
compared to wild type mice. These phenotypic differences between heterozygous and
knockout mice were not apparently dependent on MRF induction in response to
injury. Similarly, pharmacological disruption of Rev-Erb suppressive activity in
injured muscle accelerated regenerative repair in response to acute injury.
CONCLUSIONS: Disrupting Rev-Erb activity in injured muscle accelerates
regenerative muscle repair/differentiation through transcriptional de-repression
of myogenic programs. Rev-Erb, therefore, may be a potent therapeutic target for
a myriad of muscular disorders.
PMID- 28702327
TI - Loss of ADAMTS5 enhances brown adipose tissue mass and promotes browning of white
adipose tissue via CREB signaling.
AB - OBJECTIVE: A potential strategy to treat obesity - and the associated metabolic
consequences - is to increase energy expenditure. This could be achieved by
stimulating thermogenesis through activation of brown adipose tissue (BAT) and/or
the induction of browning of white adipose tissue (WAT). Over the last years, it
has become clear that several metalloproteinases play an important role in
adipocyte biology. Here, we investigated the potential role of ADAMTS5. METHODS:
Mice deficient in ADAMTS5 (Adamts5-/-) and wild-type (Adamts5+/+) littermates
were kept on a standard of Western-type diet for 15 weeks. Energy expenditure and
heat production was followed by indirect calorimetry. To activate thermogenesis,
mice were treated with the beta3-adrenergic receptor (beta3-AR) agonist CL
316,243 or alternatively, exposed to cold for 2 weeks. RESULTS: Compared to
Adamts5+/+ mice, Adamts5-/- mice have significantly more interscapular BAT and
marked browning of their subcutaneous (SC) WAT. Thermogenic pathway analysis
indicated, in the absence of ADAMTS5, enhanced beta3-AR signaling via activation
of the cAMP response element-binding protein (CREB). Additional beta3-AR
stimulation with CL-316,243 promoted browning of WAT in Adamts5+/+ mice but had
no additive effect in Adamts5-/- mice. However, cold exposure induced more
pronounced browning of WAT in Adamts5-/- mice. CONCLUSIONS: These data indicate
that ADAMTS5 plays a functional role in development of BAT and browning of WAT.
Hence, selective targeting of ADAMTS5 could provide a novel therapeutic strategy
for treatment/prevention of obesity and metabolic diseases.
PMID- 28702328
TI - ASK1 (MAP3K5) is transcriptionally upregulated by E2F1 in adipose tissue in
obesity, molecularly defining a human dys-metabolic obese phenotype.
AB - OBJECTIVE: Obesity variably disrupts human health, but molecular-based patients'
health-risk stratification is limited. Adipose tissue (AT) stresses may link
obesity with metabolic dysfunction, but how they signal in humans remains poorly
characterized. We hypothesized that a transcriptional AT stress-signaling cascade
involving E2F1 and ASK1 (MAP3K5) molecularly defines high-risk obese subtype.
METHODS: ASK1 expression in human AT biopsies was determined by real-time PCR
analysis, and chromatin immunoprecipitation (ChIP) adopted to AT explants was
used to evaluate the binding of E2F1 to the ASK1 promoter. Dual luciferase assay
was used to measure ASK1 promoter activity in HEK293 cells. Effects of E2F1
knockout/knockdown in adipocytes was assessed utilizing mouse-embryonal
fibroblasts (MEF)-derived adipocyte-like cells from WT and E2F1-/- mice and by
siRNA, respectively. ASK1 depletion in adipocytes was studied in MEF-derived
adipocyte-like cells from WT and adipose tissue-specific ASK1 knockout mice (ASK1
ATKO). RESULTS: Human visceral-AT ASK1 mRNA (N = 436) was associated with
parameters of obesity-related cardio-metabolic morbidity. Adjustment for E2F1
expression attenuated the association of ASK1 with fasting glucose, insulin
resistance, circulating IL-6, and lipids (triglycerides, HDL-cholesterol), even
after adjusting for BMI. Chromatin-immunoprecipitation in human-AT explants
revealed BMI-associated increased occupancy of the ASK1 promoter by E2F1 (r2 =
0.847, p < 0.01). In adipocytes, siRNA-mediated E2F1-knockdown, and MEF-derived
adipocytes of E2F1-knockout mice, demonstrated decreased ASK1 expression and
signaling to JNK. Mutation/truncation of an E2F1 binding site in hASK1 promoter
decreased E2F1-induced ASK1 promoter activity, whereas E2F1-mediated
sensitization of ASK1 promoter to further activation by TNFalpha was inhibited by
JNK-inhibitor. Finally, MEF-derived adipocytes from adipocyte-specific ASK1
knockout mice exhibited lower leptin and higher adiponectin expression and
secretion, and resistance to the effects of TNFalpha. CONCLUSIONS: AT E2F1 -ASK1
molecularly defines a metabolically-detrimental obese sub-phenotype.
Functionally, it may negatively affect AT endocrine function, linking AT stress
to whole-body metabolic dysfunction.
PMID- 28702329
TI - Metformin causes a futile intestinal-hepatic cycle which increases energy
expenditure and slows down development of a type 2 diabetes-like state.
AB - OBJECTIVE: Metformin, the first line drug for treatment of type 2 diabetes,
suppresses hepatic gluconeogenesis and reduces body weight in patients, the
latter by an unknown mechanism. METHODS: Mice on a high fat diet were
continuously fed metformin in a therapeutically relevant dose, mimicking a
retarded formulation. RESULTS: Feeding metformin in pharmacologically relevant
doses to mice on a high fat diet normalized HbA1c levels and ameliorated glucose
tolerance, as expected, but also considerably slowed down weight gain. This was
due to increased energy expenditure, since food intake was unchanged and
locomotor activity was even decreased. Metformin caused lactate accumulation in
the intestinal wall and in portal venous blood but not in peripheral blood or the
liver. Increased conversion of glucose-1-13C to glucose-1,6-13C under metformin
strongly supports a futile cycle of lactic acid production in the intestinal
wall, and usage of the produced lactate for gluconeogenesis in liver.
CONCLUSIONS: The reported glucose-lactate-glucose cycle is a highly energy
consuming process, explaining the beneficial effects of metformin given
continuously on the development of a type 2 diabetic-like state in our mice.
PMID- 28702331
TI - Uncoupling protein 2 regulates daily rhythms of insulin secretion capacity in
MIN6 cells and isolated islets from male mice.
AB - OBJECTIVE: Upregulation of uncoupling protein 2 (UCP2) is associated with
impaired glucose-stimulated insulin secretion (GSIS), which is thought to be an
important contributor to pathological beta cell failure in obesity and type 2
diabetes (T2D); however, the physiological function of UCP2 in the beta cell
remains undefined. It has been suggested, but not yet tested, that UCP2 plays a
physiological role in beta cells by coordinating insulin secretion capacity with
anticipated fluctuating nutrient supply, such that upregulation of UCP2 in the
inactive/fasted state inhibits GSIS as a mechanism to prevent hypoglycemia.
Therefore, we hypothesized that daily cycles of GSIS capacity are dependent on
rhythmic and predictable patterns of Ucp2 gene expression such that low Ucp2 in
the active/fed phase promotes maximal GSIS capacity, whereas elevated Ucp2
expression in the inactive/fasted phase supresses GSIS capacity. We further
hypothesized that rhythmic Ucp2 expression is required for the maintenance of
glucose tolerance over the 24 h cycle. METHODS: We used synchronized MIN6 clonal
beta cells and isolated mouse islets from wild type (C57BL6) and mice with beta
cell knockout of Ucp2 (Ucp2-betaKO; and respective Ins2-cre controls) to
determine the endogenous expression pattern of Ucp2 over 24 h and its impact on
GSIS capacity and glucose tolerance over 24 h. RESULTS: A dynamic pattern of Ucp2
mRNA expression was observed in synchronized MIN6 cells, which showed a
reciprocal relationship with GSIS capacity in a time-of-day-specific manner. GSIS
capacity was suppressed in islets isolated from wild type and control mice during
the light/inactive phase of the daily cycle; a suppression that was dependent on
Ucp2 in the beta cell and was lost in islets isolated from Ucp2-betaKO mice or
wild type islets treated with a UCP2 inhibitor. Finally, suppression of GSIS
capacity by UCP2 in the light phase was required for the maintenance of normal
patterns of glucose tolerance. CONCLUSIONS: Our study suggests that Ucp2/UCP2 in
the beta cell is part of an important, endogenous, metabolic regulator that
controls the temporal capacity of GSIS over the course of the day/night cycle,
which, in turn, regulates time-of-day glucose tolerance. Targeting Ucp2/UCP2 as a
therapeutic in type 2 diabetes or any other metabolic condition must take into
account the rhythmic nature of its expression and its impact on glucose tolerance
over 24 h, specifically during the inactive/fasted phase.
PMID- 28702330
TI - Neonatal GLP1R activation limits adult adiposity by durably altering hypothalamic
architecture.
AB - OBJECTIVE: Adult obesity risk is influenced by alterations to fetal and neonatal
environments. Modifying neonatal gut or neurohormone signaling pathways can have
negative metabolic consequences in adulthood. Here we characterize the effect of
neonatal activation of glucagon like peptide-1 (GLP-1) receptor (GLP1R) signaling
on adult adiposity and metabolism. METHODS: Wild type C57BL/6 mice were injected
with 1 nmol/kg Exendin-4 (Ex-4), a GLP1R agonist, for 6 consecutive days after
birth. Growth, body composition, serum analysis, energy expenditure, food intake,
and brain and fat pad histology and gene expression were assessed at multiple
time points through 42 weeks. Similar analyses were conducted in a Glp1r
conditional allele crossed with a Sim1Cre deleter strain to produce
Sim1Cre;Glp1rloxP/loxP mice and control littermates. RESULTS: Neonatal
administration of Ex-4 reduced adult body weight and fat mass, increased energy
expenditure, and conferred protection from diet-induced obesity in female mice.
This was associated with induction of brown adipose genes and increased
noradrenergic fiber density in parametrial white adipose tissue (WAT). We further
observed durable alterations in orexigenic and anorexigenic projections to the
paraventricular hypothalamic nucleus (PVH). Genetic deletion of Glp1r in the PVH
by Sim1-Cre abrogated the impact of neonatal Ex-4 on adult body weight, WAT
browning, and hypothalamic architecture. CONCLUSION: These observations suggest
that the acute activation of GLP1R in neonates durably alters hypothalamic
architecture to limit adult weight gain and adiposity, identifying GLP1R as a
therapeutic target for obesity prevention.
PMID- 28702333
TI - Cough syncope induced by post nasal drip successfully managed by Gabapentin.
AB - Syncope is a common complaint in both neurology clinic and emergency department.
It is defined as transient loss of consciousness with loss of postural tone,
which is usually self-limited and followed by a spontaneous recovery. Our report
describes a case of cough syncope resulting from chronic intractable cough caused
by post nasal drip. Although his experience was debilitating, we were able to
control his symptoms significantly using a small dose of Gabapentin. This dose is
much lower when compared with the already established licensed indicated higher
doses used for the treatment of neuropathic pain and epilepsy. Cough syncope is a
demanding condition that results in comprehensive costly investigations. In
addition, cough syncope could be misinterpreted as epilepsy by the treating team.
Pulmonologists should be aware of the use of Gabapentin as the management of
cough refractory to standard antitussive therapy. Further studies are needed to
assess the effectiveness of low doses of Gabapentin in the management of chronic
cough.
PMID- 28702332
TI - Dysregulation of a novel miR-23b/27b-p53 axis impairs muscle stem cell
differentiation of humans with type 2 diabetes.
AB - OBJECTIVE: MicroRNAs (miRNAs) are increasingly recognized as fine-tuning
regulators of metabolism, and are dysregulated in several disease conditions.
With their capacity to rapidly change gene expression, miRNAs are also important
regulators of development and cell differentiation. In the current study, we
describe an impaired myogenic capacity of muscle stem cells isolated from humans
with type 2 diabetes (T2DM) and assess whether this phenotype is regulated by
miRNAs. METHODS: We measured global miRNA expression during in vitro
differentiation of muscle stem cells derived from T2DM patients and healthy
controls. RESULTS: The mir-23b/27b cluster was downregulated in the cells of the
patients, and a pro-myogenic effect of these miRNAs was mediated through the p53
pathway, which was concordantly dysregulated in the muscle cells derived from
humans with T2DM. CONCLUSIONS: Our results indicate that we have identified a
novel pathway for coordination of myogenesis, the miR-23b/27b-p53 axis that, when
dysregulated, potentially contributes to a sustained muscular dysfunction in
T2DM.
PMID- 28702334
TI - An uncommon cause of pneumonia: The golden diagnosis.
AB - A 28-year-old sub-Saharan African Italian non-smoker male presented with signs
and symptoms of pneumonia and respiratory failure. Despite antibiotic treatment
he experienced a significant worsening of respiratory conditions and admission to
intensive care unit. He thus underwent chest computed tomography followed by
fiberopict bronchoscopy with bronchoalveolar lavage whose macroscopic examination
led to the diagnosis of acute chest syndrome. A brief literature review was
conducted to discuss the first manifestation of this disease.
PMID- 28702335
TI - An undiagnosed pleural effusion with surprising consequences.
AB - We present the case of a 43-year-old Italian woman with a left undiagnosed
pleural effusion, which in subsequent months presented a clinically unexpected
evolution with the appearance at first of a right wrist tenosynovitis and
subsequently a bilateral lung involvement caused by M. Tuberculosis. With this
case report, we would like to underline the importance of making a correct
diagnosis of any pleural effusion as soon as possible by at least a
thoracocentesis. If untreated, tuberculosis may easily disseminate to other
organs. Some considerations and suggestions for antibiotic treatment of pleural
effusion will also be given, since many antibiotics have some anti-tuberculosis
effect and may delay the diagnosis of this infectious disease.
PMID- 28702336
TI - Progressive subcutaneous emphysema. A rare finding: Pneumorrhachis.
AB - Pneumorrhachis is a rare phenomenon which may be caused by trauma, intracraneal
infection, pneumomediastinum or iatrogenic factors. Presence of air in the spinal
canal is reported in most cases. In this article, we report a case with PR in the
spinal canal without any neurological deficit, which developed secondary to
subcutaneous emphysema.
PMID- 28702337
TI - Linear EBUS-guided fiducial marker placement to guide radiotherapy for
endobronchial, radiographically occult synchronous primary squamous cell
carcinoma of the lung.
AB - Radiation therapy has emerged as a useful alternative therapy for patients with
early-stage, non-resectable lung cancer. In patients whose malignancies are
difficult to localize on computed tomography imaging, such therapy becomes
difficult. Fiducial markers are frequently placed in peripheral pulmonary lesions
to assist radiation therapy. Although placement of markers under linear
endobronchial ultrasonography within mediastinal and hilar lymph nodes has been
reported, no strategy has been described to assist radiotherapy of purely
endobronchial tumors. We present a case of bilateral, unresectable,
radiographically occult endobronchial squamous cell carcinoma treated with
radiotherapy guided by fiducial markers placed under linear endobronchial
ultrasonographic guidance. The patient subsequently underwent intensity-modified
radiation therapy to both lesions with pathologic complete response. Linear
endobronchial ultrasound is a promising tool for placement of markers to guide
radiation therapy of these difficult-to-treat lesions.
PMID- 28702338
TI - "Liquid elbows" due to afatinib administration.
AB - Non-small cell lung cancer adenocarcinoma in the past decade has targeted
therapies as the cornerstone for therapy. In specific patients with epidermal
growth factor receptor mutation have three different therapy approaches with the
tyrosine kinase inhibitors: erlotinib, gefitinib and afatinib. Nowadays we can
use tyrosine kinase inhibitors as second line treatment for squamous cell
carcinoma. We present a case with a patient with squamous cell carcinoma
receiving afatinib tyrosine kinase inhibitor who presented elbow bursitis or
olecranon bursitis in both elbows.
PMID- 28702339
TI - Structured Light Plethysmography (SLP): Management and follow up of a paediatric
patient with pneumonia.
AB - Structured Light Plethysmography (SLP) is a non-invasive method to study chest
and abdominal movement during breathing and can identify abnormal contributions
of the different regions of the chest. M.D hospitalized for pneumonia, underwent
SLP and spirometry at admission (T0), after 48 hours (T1), and after one month
(T2). SLP parameters showed expiratory flow limitation, information consistent
with the spirometric parameters collected, and reduced motion in the area
effected by pneumonia, with improvement and normalization at T1 and T2. This
method gave useful information about the contribution to the respiratory movement
of the lung area affected by pneumonia so we can speculate a possible use in the
follow-up of children affected by pneumonia or other respiratory diseases, and
who are not able to perform a spirometric test.
PMID- 28702340
TI - Characteristics of Mycobacterium avium complex (MAC) pulmonary disease in
previously treated lung cancer patients.
AB - INTRODUCTION: Mycobacterium avium complex (MAC) is responsible for a large
portion of non-tuberculous mycobacterial (NTM) infections worldwide. Host factors
such as active malignancy, immunosuppression, chronic obstructive pulmonary
disease (COPD) and bronchiectasis increase the risk of MAC infection. However,
the relationship between previously treated lung cancer with subsequent
development of MAC pulmonary disease and treatment outcomes have not been
previously studied. METHODS: We retrospectively identified all patients with lung
cancer and MAC pulmonary disease documented in medical records at Mayo Clinic
between January 2005 and October 2016. Patients who were diagnosed with MAC
pulmonary disease before or at the time of lung cancer diagnosis were excluded.
Patients meeting all inclusion criteria underwent chart review for prior
oncologic treatments, clinical characteristics, and MAC treatment response.
RESULTS: We identified 13 patients with MAC pulmonary disease and prior lung
cancer, including 4 men and 9 women. Eight patients had structural lung disease
that can predispose to MAC pulmonary disease, including bronchiectasis (23.0%)
and COPD (46.2%). Four (30.8%) had no apparent immunosuppression or other risk
factor(s) for MAC pulmonary disease. Primary pulmonary malignancies included
pulmonary carcinoid, adenocarcinoma, and squamous cell carcinoma. Ten (76.9%)
patients were started on antimicrobial treatment for MAC, and 8 (61.5%) patients
completed MAC treatment with 6 (46.1%) patients achieving symptomatic
improvement. CONCLUSION: MAC pulmonary disease in previously treated lung cancer
can occur without apparent risk factors for this NTM infection. Symptomatic
improvement with MAC antimicrobial therapy appears to be lower than expected but
comorbidities might influence outcomes in this patient population.
PMID- 28702341
TI - Severe dyspnea in a patient with neurofibromatosis type 1.
AB - Neurofibromatosis type 1 (NF1) is a genetic disease in which pulmonary
complications are rare, but severe, especially pulmonary hypertension (PH). The
mechanisms underlying the onset of PH in patients with NF1 are unclear and might
be multifactorial. In particular, the frequent presence of pulmonary parenchymal
lesions makes etiological diagnosis of PH difficult. We describe here the case of
a patient with NF1 admitted to our clinic with dyspnea and right heart failure
revealing severe pre-capillary PH. Parenchymal lesions were mild and PH was
attributed to pulmonary vascular involvement. Clinical and hemodynamic conditions
of the patient improved under pulmonary arterial hypertension-specific
combination therapy. This case suggests that treatment of PH due to pulmonary
vascular involvement in NF1 may be aligned with recommendations for PAH
treatment.
PMID- 28702342
TI - Pulmonary manifestation of Plasmodium falciparum malaria: Case reports and review
of the literature.
AB - Pulmonary complications, including acute respiratory distress syndrome (ARDS),
are well described in P. falciparum (PF) and to a lesser extent in other malaria
species. In non-endemic areas, malaria diagnosis may be overlooked; if a thorough
travel history is not obtained on all patients with acute febrile illness. Three
patients with malaria associated respiratory distress were admitted to our
intensive care unit. The diagnosis was delayed; however, all patients received
artesunate and intensive therapy with a satisfactory outcome. One patient
presented with respiratory disease while the others developed ARDS during or
following appropriate therapy. Similarly, level of parasitemia was variable
ranging from undetectable to over 5%. Variability in timing and severity of
illness is exciting and gives emphasis to the different pathological processes
contemplated in this complication.
PMID- 28702343
TI - EB virus reactivation triggers thrombotic thrombocytopenic purpura in a healthy
adult.
AB - Thrombotic thrombocytopenic purpura (TTP) is rare but life-threatening disease,
characterized typically by microangiopathic hemolytic anemia (MAHA), profound
peripheral thrombocytopenia and severe deficiency in the von Willebrand factor
cleaving prortease ADAMTS13. It has been reported that acquired immune TTP is
closely associated with human immunodeficiency virus infection and influenza
infection or vaccination. However, it has not been reported to be associated with
Epstein Barr Virus infection or reactivation. We herein report a first case of
acquired TTP associated with EBV reactivation in an otherwise healthy adult.
PMID- 28702344
TI - Directional information flow in patients with Alzheimer's disease. A source-space
resting-state MEG study.
AB - In a recent magnetoencephalography (MEG) study, we found posterior-to-anterior
information flow over the cortex in higher frequency bands in healthy subjects,
with a reversed pattern in the theta band. A disruption of information flow may
underlie clinical symptoms in Alzheimer's disease (AD). In AD, highly connected
regions (hubs) in posterior areas are mostly disrupted. We therefore hypothesized
that in AD the information flow from these hub regions would be disturbed. We
used resting-state MEG recordings from 27 early-onset AD patients and 26 healthy
controls. Using beamformer-based virtual electrodes, we estimated neuronal
oscillatory activity for 78 cortical regions of interest (ROIs) and 12
subcortical ROIs of the AAL atlas, and calculated the directed phase transfer
entropy (dPTE) as a measure of information flow between these ROIs. Group
differences were evaluated using permutation tests and, for the AD group,
associations between dPTE and general cognition or CSF biomarkers were determined
using Spearman correlation coefficients. We confirmed the previously reported
posterior-to-anterior information flow in the higher frequency bands in the
healthy controls, and found it to be disturbed in the beta band in AD. Most
prominently, the information flow from the precuneus and the visual cortex,
towards frontal and subcortical structures, was decreased in AD. These
disruptions did not correlate with cognitive impairment or CSF biomarkers. We
conclude that AD pathology may affect the flow of information between brain
regions, particularly from posterior hub regions, and that changes in the
information flow in the beta band indicate an aspect of the pathophysiological
process in AD.
PMID- 28702345
TI - Hierarchical disruption in the Bayesian brain: Focal epilepsy and brain networks.
AB - In this opinion paper, we describe a combined view of functional and effective
brain connectivity along with the free-energy principle for investigating
persistent disruptions in brain networks of patients with focal epilepsy. These
changes are likely reflected in effective connectivity along the cortical
hierarchy and construct the basis of increased local functional connectivity in
focal epilepsy. We propose a testable framework based on dynamic causal modelling
and functional connectivity analysis with the capacity of explaining commonly
observed connectivity changes during interictal periods. We then hypothesise
their possible relation with disrupted free-energy minimisation in the Bayesian
brain. This may offer a new approach for neuroimaging to specifically develop and
address hypotheses regarding the network pathomechanisms underlying epileptic
phenotypes.
PMID- 28702346
TI - Automatic detection and visualisation of MEG ripple oscillations in epilepsy.
AB - High frequency oscillations (HFOs, 80-500 Hz) in invasive EEG are a biomarker for
the epileptic focus. Ripples (80-250 Hz) have also been identified in non
invasive MEG, yet detection is impeded by noise, their low occurrence rates, and
the workload of visual analysis. We propose a method that identifies ripples in
MEG through noise reduction, beamforming and automatic detection with minimal
user effort. We analysed 15 min of presurgical resting-state interictal MEG data
of 25 patients with epilepsy. The MEG signal-to-noise was improved by using a
cross-validation signal space separation method, and by calculating ~ 2400
beamformer-based virtual sensors in the grey matter. Ripples in these sensors
were automatically detected by an algorithm optimized for MEG. A small subset of
the identified ripples was visually checked. Ripple locations were compared with
MEG spike dipole locations and the resection area if available. Running the
automatic detection algorithm resulted in on average 905 ripples per patient, of
which on average 148 ripples were visually reviewed. Reviewing took approximately
5 min per patient, and identified ripples in 16 out of 25 patients. In 14
patients the ripple locations showed good or moderate concordance with the MEG
spikes. For six out of eight patients who had surgery, the ripple locations
showed concordance with the resection area: 4/5 with good outcome and 2/3 with
poor outcome. Automatic ripple detection in beamformer-based virtual sensors is a
feasible non-invasive tool for the identification of ripples in MEG. Our method
requires minimal user effort and is easily applicable in a clinical setting.
PMID- 28702347
TI - TDCS modulates cortical excitability in patients with disorders of consciousness.
AB - Transcranial direct current stimulation (tDCS) has been reported to be a
promising technique for consciousness improvement for patients with disorders of
consciousness (DOC). However, there has been no direct electrophysiological
evidence to demonstrate the efficacy of tDCS on patients with DOC. Therefore, we
aim to measure the cortical excitability changes induced by tDCS in patients with
DOC, to find electrophysiological evidence supporting the therapeutic efficacy of
tDCS on patients with DOC. In this study, we enrolled sixteen patients with DOC,
including nine vegetative state (VS) and seven minimally conscious state (MCS)
(six females and ten males). TMS-EEG was applied to assess cortical excitability
changes after twenty minutes of anodal tDCS of the left dorsolateral prefrontal
cortex. Global cerebral excitability were calculated to quantify cortical
excitability in the temporal domain: four time intervals (0-100, 100-200, 200
300, 300-400 ms). Then local cerebral excitability in the significantly altered
time windows were investigated (frontal, left/right hemispheres, central, and
posterior). Compared to baseline and sham stimulation, we found that global
cerebral excitability increased in early time windows (0-100 and 100-200 ms) for
patients with MCS; for the patients with VS, global cerebral excitability
increased in the 0-100 ms interval but decreased in the 300-400 ms interval. The
local cerebral excitability was significantly different between MCS and VS. The
results indicated that tDCS can effectively modulate the cortical excitability of
patients with DOC; and the changes in excitability in temporal and spatial
domains are different between patients with MCS and those with VS.
PMID- 28702348
TI - Predicting pain relief: Use of pre-surgical trigeminal nerve diffusion metrics in
trigeminal neuralgia.
AB - Trigeminal neuralgia (TN) is a chronic neuropathic facial pain disorder that
commonly responds to surgery. A proportion of patients, however, do not benefit
and suffer ongoing pain. There are currently no imaging tools that permit the
prediction of treatment response. To address this paucity, we used diffusion
tensor imaging (DTI) to determine whether pre-surgical trigeminal nerve
microstructural diffusivities can prognosticate response to TN treatment. In 31
TN patients and 16 healthy controls, multi-tensor tractography was used to
extract DTI-derived metrics-axial (AD), radial (RD), mean diffusivity (MD), and
fractional anisotropy (FA)-from the cisternal segment, root entry zone and
pontine segment of trigeminal nerves for false discovery rate-corrected Student's
t-tests. Ipsilateral diffusivities were bootstrap resampled to visualize group
level diffusivity thresholds of long-term response. To obtain an individual-level
statistical classifier of surgical response, we conducted discriminant function
analysis (DFA) with the type of surgery chosen alongside ipsilateral measurements
and ipsilateral/contralateral ratios of AD and RD from all regions of interest as
prediction variables. Abnormal diffusivity in the trigeminal pontine fibers,
demonstrated by increased AD, highlighted non-responders (n = 14) compared to
controls. Bootstrap resampling revealed three ipsilateral diffusivity thresholds
of response-pontine AD, MD, cisternal FA-separating 85% of non-responders from
responders. DFA produced an 83.9% (71.0% using leave-one-out-cross-validation)
accurate prognosticator of response that successfully identified 12/14 non
responders. Our study demonstrates that pre-surgical DTI metrics can serve as a
highly predictive, individualized tool to prognosticate surgical response. We
further highlight abnormal pontine segment diffusivities as key features of
treatment non-response and confirm the axiom that central pain does not commonly
benefit from peripheral treatments.
PMID- 28702349
TI - Distinct multivariate brain morphological patterns and their added predictive
value with cognitive and polygenic risk scores in mental disorders.
AB - The brain underpinnings of schizophrenia and bipolar disorders are
multidimensional, reflecting complex pathological processes and causal pathways,
requiring multivariate techniques to disentangle. Furthermore, little is known
about the complementary clinical value of brain structural phenotypes when
combined with data on cognitive performance and genetic risk. Using data-driven
fusion of cortical thickness, surface area, and gray matter density maps (GMD),
we found six biologically meaningful patterns showing strong group effects,
including four statistically independent multimodal patterns reflecting co
occurring alterations in thickness and GMD in patients, over and above two other
independent patterns of widespread thickness and area reduction. Case-control
classification using cognitive scores alone revealed high accuracy, and adding
imaging features or polygenic risk scores increased performance, suggesting their
complementary predictive value with cognitive scores being the most sensitive
features. Multivariate pattern analyses reveal distinct patterns of brain
morphology in mental disorders, provide insights on the relative importance
between brain structure, cognitive and polygenetic risk score in classification
of patients, and demonstrate the importance of multivariate approaches in
studying the pathophysiological substrate of these complex disorders.
PMID- 28702350
TI - Reading related white matter structures in adolescents are influenced more by
dysregulation of emotion than behavior.
AB - Mood disorders and behavioral are broad psychiatric diagnostic categories that
have different symptoms and neurobiological mechanisms, but share some
neurocognitive similarities, one of which is an elevated risk for reading
deficit. Our aim was to determine the influence of mood versus behavioral
dysregulation on reading ability and neural correlates supporting these skills in
youth, using diffusion tensor imaging in 11- to 17-year-old children and youths
with mood disorders or behavioral disorders and age-matched healthy controls. The
three groups differed only in phonological processing and passage comprehension.
Youth with mood disorders scored higher on the phonological test but had lower
comprehension scores than children with behavioral disorders and controls;
control participants scored the highest. Correlations between fractional
anisotropy and phonological processing in the left Arcuate Fasciculus showed a
significant difference between groups and were strongest in behavioral disorders,
intermediate in mood disorders, and lowest in controls. Correlations between
these measures in the left Inferior Longitudinal Fasciculus were significantly
greater than in controls for mood but not for behavioral disorders. Youth with
mood disorders share a deficit in the executive-limbic pathway (Arcuate
Fasciculus) with behavioral-disordered youth, suggesting reduced capacity for
engaging frontal regions for phonological processing or passage comprehension
tasks and increased reliance on the ventral tract (e.g., the Inferior
Longitudinal Fasciculus). The low passage comprehension scores in mood disorder
may result from engaging the left hemisphere. Neural pathways for reading differ
mainly in executive-limbic circuitry. This new insight may aid clinicians in
providing appropriate intervention for each disorder.
PMID- 28702351
TI - Activation of dominant hemisphere association cortex during naming as a function
of cognitive performance in mild traumatic brain injury: Insights into mechanisms
of lexical access.
AB - Patients with a history of mild traumatic brain injury (mTBI) and objective
cognitive deficits frequently experience word finding difficulties in normal
conversation. We sought to improve our understanding of this phenomenon by
determining if the scores on standardized cognitive testing are correlated with
measures of brain activity evoked in a word retrieval task (confrontational
picture naming). The study participants (n = 57) were military service members
with a history of mTBI. The General Memory Index (GMI) determined after
administration of the Rivermead Behavioral Memory Test, Third Edition, was used
to assign subjects to three groups: low cognitive performance (Group 1: GMI <=
87, n = 18), intermediate cognitive performance (Group 2: 88 <= GMI <= 99, n =
18), and high cognitive performance (Group 3: GMI >= 100, n = 21).
Magnetoencephalography data were recorded while participants named eighty
pictures of common objects. Group differences in evoked cortical activity were
observed relatively early (within 200 ms from picture onset) over a distributed
network of left hemisphere cortical regions including the fusiform gyrus, the
entorhinal and parahippocampal cortex, the supramarginal gyrus and posterior part
of the superior temporal gyrus, and the inferior frontal and rostral middle
frontal gyri. Differences were also present in bilateral cingulate cortex and
paracentral lobule, and in the right fusiform gyrus. All differences reflected a
lower amplitude of the evoked responses for Group 1 relative to Groups 2 and 3.
These findings may indicate weak afferent inputs to and within an extended
cortical network including association cortex of the dominant hemisphere in
patients with low cognitive performance. The association between word finding
difficulties and low cognitive performance may therefore be the result of a
diffuse pathophysiological process affecting distributed neuronal networks
serving a wide range of cognitive processes. These findings also provide support
for a parallel processing model of lexical access.
PMID- 28702352
TI - Automatized smoking-related action schemata are reflected by reduced fMRI
activity in sensorimotor brain regions of smokers.
AB - In the later stages of addiction, automatized processes play a prominent role in
guiding drug-seeking and drug-taking behavior. However, little is known about the
neural correlates of automatized drug-taking skills and drug-related action
knowledge in humans. We employed functional magnetic resonance imaging (fMRI)
while smokers and non-smokers performed an orientation affordance task, where
compatibility between the hand used for a behavioral response and the spatial
orientation of a priming stimulus leads to shorter reaction times resulting from
activation of the corresponding motor representations. While non-smokers
exhibited this behavioral effect only for control objects, smokers showed the
affordance effect for both control and smoking-related objects. Furthermore,
smokers exhibited reduced fMRI activation for smoking-related as compared to
control objects for compatible stimulus-response pairings in a sensorimotor brain
network consisting of the right primary motor cortex, supplementary motor area,
middle occipital gyrus, left fusiform gyrus and bilateral cingulate gyrus. In the
incompatible condition, we found higher fMRI activation in smokers for smoking
related as compared to control objects in the right primary motor cortex,
cingulate gyrus, and left fusiform gyrus. This suggests that the activation and
performance of deeply embedded, automatized drug-taking schemata employ less
brain resources. This might reduce the threshold for relapsing in individuals
trying to abstain from smoking. In contrast, the interruption or modification of
already triggered automatized action representations require increased neural
resources.
PMID- 28702353
TI - Longitudinal MR spectroscopy of neurodegeneration in multiple sclerosis with
diffusion of the intra-axonal constituent N-acetylaspartate.
AB - Multiple sclerosis (MS) is a pathologically complex CNS disease: inflammation,
demyelination, and neuroaxonal degeneration occur concurrently and may depend on
one another. Current therapies are aimed at the immune-mediated, inflammatory
destruction of myelin, whereas axonal degeneration is ongoing and not
specifically targeted. Diffusion-weighted magnetic resonance spectroscopy can
measure the diffusivity of metabolites in vivo, such as the axonal/neuronal
constituent N-acetylaspartate, allowing compartment-specific assessment of
disease-related changes. Previously, we found significantly lower N
acetylaspartate diffusivity in people with MS compared to healthy controls (Wood
et al., 2012) suggesting that this technique can measure axonal degeneration and
could be useful in developing neuroprotective agents. In this longitudinal study,
we found that N-acetylaspartate diffusivity decreased by 8.3% (p < 0.05) over 6
months in participants who were experiencing clinical or MRI evidence of
inflammatory activity (n = 13), whereas there was no significant change in N
acetylaspartate diffusivity in the context of clinical and radiological stability
(n = 6). As N-acetylaspartate diffusivity measurements are thought to more
specifically reflect the intra-axonal space, these data suggest that N
acetylaspartate diffusivity can report on axonal health on the background of
multiple pathological processes in MS, both cross-sectionally and longitudinally.
PMID- 28702355
TI - Whole genome sequencing and annotation of halophilic Salinicoccus sp. BAB 3246
isolated from the coastal region of Gujarat.
AB - Salinicoccus sp. BAB 3246 is a halophilic bacterium isolated from a marine water
sample collected from the coastal region of Gujarat, India, from a surface water
stream. Based on 16sRNA sequencing, the organism was identified as Salinicoccus
sp. BAB 3246 (Genebank ID: KF889285). The present work was performed to determine
the whole genome sequence of the organism using Ion Torrent PGM platform followed
by assembly using the CLC genomics workbench and genome annotation using RAST,
BASys and MaGe. The complete genome sequence was 713,204 bp identified by with
second largest size for Salinicoccus sp. reported in the NCBI genome database. A
total of 652 degradative pathways were identified by KEGG map analysis.
Comparative genomic analysis revealed Salinicoccus sp. BAB 3246 as most highly
related to Salinicoccus halodurans H3B36. Data mining identified stress response
genes and operator pathway for degradation of various environmental pollutants.
Annotation data and analysis indicate potential use in pollution control in
industrial influent and saline environment.
PMID- 28702354
TI - White matter integrity in dyskinetic cerebral palsy: Relationship with
intelligence quotient and executive function.
AB - BACKGROUND: Dyskinetic cerebral palsy (CP) is one of the most disabling motor
types of CP and has been classically associated with injury to the basal ganglia
and thalamus. Although cognitive dysfunction is common in CP, there is a paucity
of published quantitative analyses investigating the relationship between white
matter (WM) microstructure and cognition in this CP type. AIMS: This study aims
(1) to compare brain WM microstructure between people with dyskinetic CP and
healthy controls, (2) to identify brain regions where WM microstructure is
related to intelligence and (3) to identify brain regions where WM microstructure
is related to executive function in people with dyskinetic CP and (4) to identify
brain regions where the correlations are different between controls and people
with CP in IQ and executive functions. PATIENTS AND METHODS: Thirty-three
participants with dyskinetic CP (mean +/- SD age: 24.42 +/- 12.61, 15 female)
were age and sex matched with 33 controls. Participants underwent a comprehensive
neuropsychological battery to assess intelligence quotient (IQ) and four
executive function domains (attentional control, cognitive flexibility, goal
setting and information processing). Diffusion weighted MRI scans were acquired
at 3T. Voxel-based whole brain groupwise analyses were used to compare fractional
anisotropy (FA) and of the CP group to the matched controls using a general
lineal model. Further general linear models were used to identify regions where
white matter FA correlated with IQ and each of the executive function domains.
RESULTS: White matter FA was significantly reduced in the CP group in all
cerebral lobes, predominantly in regions connected with the parietal and to a
lesser extent the temporal lobes. There was no significant correlation between IQ
or any of the four executive function domains and WM microstructure in the
control group. In participants with CP, lower IQ was associated with lower FA in
all cerebral lobes, predominantly in locations that also showed reduced FA
compared to controls. Attentional control, goal setting and information
processing did not correlate with WM microstructure in the CP group. Cognitive
flexibility was associated with FA in regions known to contain connections with
the frontal lobe (such as the superior longitudinal fasciculus and cingulum) as
well as regions not known to contain tracts directly connected with the frontal
lobe (such as the posterior corona radiata, posterior thalamic radiation,
retrolenticular part of internal capsule, tapetum, body and splenium of corpus
callosum). CONCLUSION: The widespread loss in the integrity of WM tissue is
mainly located in the parietal lobe and related to IQ in dyskinetic CP.
Unexpectedly, executive functions are only related with WM microstructure in
regions containing fronto-cortical and posterior cortico-subcortical pathways,
and not being specifically related to the state of fronto-striatal pathways which
might be due to brain reorganization. Further studies of this nature may improve
our understanding of the neurobiological bases of cognitive impairments after
early brain insult.
PMID- 28702356
TI - Genome sequence of Bradyrhizobium sp. LMTR 3, a diazotrophic symbiont of Lima
bean (Phaseolus lunatus).
AB - Bradyrhizobium sp. LMTR 3 is a representative strain of one of the geno(species)
of diazotrophic symbionts associated with Lima bean (Phaseolus lunatus) in Peru.
Its 7.83 Mb genome was sequenced using the Illumina technology and found to
encode a complete set of genes required for nodulation and nitrogen fixation, and
additional genes putatively involved in root colonization. Its draft genome
sequence and annotation have been deposited at GenBank under the accession number
MAXC00000000.
PMID- 28702357
TI - A numerical analysis of a semi-dry coupling configuration in photoacoustic
computed tomography for infant brain imaging.
AB - In the application of photoacoustic human infant brain imaging, debubbled
ultrasound gel or water is commonly used as a couplant for ultrasonic transducers
due to their acoustic properties. The main challenge in using such a couplant is
its discomfort for the patient. In this study, we explore the feasibility of a
semi-dry coupling configuration to be used in photoacoustic computed tomography
(PACT) systems. The coupling system includes an inflatable container consisting
of a thin layer of Aqualene with ultrasound gel or water inside of it. Finite
element method (FEM) is used for static and dynamic structural analysis of the
proposed configuration to be used in PACT for infant brain imaging. The outcome
of the analysis is an optimum thickness of Aqualene in order to meet the weight
tolerance requirement with the least attenuation and best impedance match to
recommend for an experimental setting.
PMID- 28702358
TI - Crossing the road in time: Inequalities in older people's walking speeds.
AB - Pedestrian crossings in the UK and US require people to walk at 1.2 m/s to cross
the road in time; however a large proportion of older people do not walk this
fast, potentially discouraging walking or putting older people at risk of injury.
We use longitudinal data to investigate changes in walking speed, and ability to
cross the road in time, at older ages. 31,015 walking speed measurements were
taken from 10,249 men and women aged 60+ years in waves 1-7 of the English
Longitudinal Study of Ageing (2002-2014). Growth curve analyses were used to
model how walking speed changes with increasing age, and predicted probabilities
of being able to cross the road in time were estimated. 10% of measured walking
speeds were fast enough to cross the road in time. Walking speed declined with
age (-5.7*10-3m/s/yr (95% CI -7.6*10-3, -3.9*10-3)), and the decline accelerated
with increasing age (-0.3 *10-3m/s/yr (-0.4 *10-3, -0.3 *10-3)). Female, less
wealthy and less healthy older people had slower walking speeds. For instance,
predicted probability of crossing the road in time at age 60 was 14.8% (10.1,
18.5) and 2.7% (1.5, 3.8) for the richest and poorest men and 8.4% (6.0, 1.1) and
1.5% (0.9, 2.2) for the richest and poorest women, and at age 80 they were 7.1%
(3.6, 10.5) and 1.0% (0.3, 1.7) for the richest and poorest men and 3.7% (1.6,
5.9) and 0.5% (0.1, 0.9) for the richest and poorest women. Most older people do
not walk fast enough to cross the road in time. Even the majority of the
wealthiest and healthiest people aged 60 years and older do not walk fast enough
to cross pedestrian crossings in the allocated time. Crossing times should be
increased to allow for older peoples' slower walking speeds or other policies
considered to improve walkability, and to help avoid injuries and social
isolation.
PMID- 28702359
TI - Cerebral toxoplasmosis requiring urgent brain biopsy.
AB - A 39-yerar-old man was admitted to our hospital with behavioral disturbances and
generalized headaches. He was diagnosed with CNS toxoplasmosis after performing a
brain biopsy. He found to be HIV positive with a CD4 of 14/uL He was started on
ant toxoplasmosis along with antiretroviral therapy. He presented 6 weeks after
discharge with worsening headache thought to be related to relapse of
toxoplasmosis. However, he found to have severe anemia related to CMV-induced
gastrointestinal bleeding. He was started on anti-cytomegalovirus drugs and has
finally achieved significant improvement.
PMID- 28702360
TI - Treatment of profound thrombocytopenia in a patient with Gaucher disease type 1:
Is there a role for substrate reduction therapy.
AB - The availability of three enzyme replacement therapy (ERT) drugs and two
substrate reduction therapy (SRT) drugs to treat Gaucher disease provides an
opportunity to tailor therapies to a patient's specific clinical concerns.
However, there is a gap in the literature regarding individual drug effectiveness
in treating particular symptoms and the potential benefits of combination
treatment. This report details treatment of a patient with Gaucher disease type 1
whose main clinical concern was profound thrombocytopenia (around 20 * 109/L,
normal range: 150-450 * 109/L) with several episodes of bleeding with minimal
trauma and bruises. The patient was treated with ERT at doses up to 60 units/kg
weekly, with no improvement in platelet levels for 6 years. Subsequently, the
patient transitioned to SRT and platelet levels increased almost two fold within
the first month, and have remained stable at safe levels (30-60 * 109/L) for
almost 2.5 years at the time of publication. This report demonstrates a possible
therapeutic benefit of SRT in individual patients who do not meet therapeutic
goals in terms of thrombocytopenia after a considerable period on first-line ERT
treatment. Oral administration of SRT also improved this patient's quality of
life allowing discontinuation of weekly ERT infusions, which better accommodated
her demanding career and busy lifestyle.
PMID- 28702361
TI - Home infusion program with enzyme replacement therapy for Fabry disease: The
experience of a large Italian collaborative group.
AB - Fabry disease (FD) [OMIM 301500] is an X-linked lysosomal storage disorder caused
by a deficiency of the lysosomal enzyme alpha-galactosidase A, resulting in
progressive multisystem accumulation of globotriaosylceramide (Gb3). Although the
introduction of Enzyme Replacement Therapy (ERT) resulted in a variety of
clinical benefits, life-long intravenous (IV) treatment with ERT with an every
other week schedule, may interfere with daily life activities and impact on QoL.
We report here a multicentric, observational, longitudinal data analysis on a
large cohort of 85 Italian FD patients (45 males, 40 females) from 11 out of 20
Italian regions, who received a cumulative number of 4269 home infusions of
agalsidase alfa. For the whole cohort, the average duration of home therapy was 1
year and 11 months (range 3 months-4 years and 6 months), and during this period,
compliance to treatment (number of infusions performed vs scheduled) reached
100%. The EQ-5 VAS scale was administered to patients to evaluate the self
reported QoL, 58% of patients showing an increase of EQ-5 VAS score at follow up
compared to baseline (home treatment start) or remaining stable. A mild increase
of average disease severity, measured through Mainz Severity Score Index (MSSI),
was found during hospital treatment (p < 0,007), while it remained stable between
the first home therapy infusion and last follow up. Interestingly, 4 out of 7
(57%) patients, showing an improvement in FD-related clinical status after
starting home therapy, had previously a sub-optimal compliance to treatment
during the period of hospital treatment management. Only 4 adverse non serious
reactions (0,093%) were reported totally in 2 patients during home treatment. We
conclude that home infusions in eligible patients with FD are safe, contribute to
improve treatment compliance and therapeutic clinical outcomes, and may have a
positive impact on self-perceived QoL.
PMID- 28702362
TI - A Unique Case of Spontaneous Bilateral Renal Subcapsular Urinoma Secondary to
High Pressure Chronic Retention of Urine.
AB - Subcapsular urinomas have been reported in the past as a presenting feature of
ureteric or bladder outlet obstruction, generally in children, and often
associated with neurogenic bladders. We describe a case of spontaneous
asymptomatic bilateral subcapsular urinomas in an adult male with high pressure
retention of urine secondary to bladder outlet obstruction. An extensive
literature review shows this to be a unique case.
PMID- 28702363
TI - A Case of Bacillus Calmette-Guerin Cystitis Diagnosed with a Novel Loop-mediated
Isothermal Amplification Method.
AB - Intravesical bacillus Calmette-Guerin (BCG) instillation is broadly used to
prevent bladder cancer recurrence or to treat carcinoma in situ. BCG infection is
rare but can cause serious problems because this strain has intrinsic resistance
to pyrazinamide, a first-line anti-tuberculosis drug. Furthermore, there had been
no specific and easy procedure accurately diagnosing BCG infection. In this case
report we present the first case of BCG cystitis diagnosed with a newly developed
easy-to-use diagnostic procedure using the loop-mediated isothermal amplification
method.
PMID- 28702364
TI - Robotic Assisted Common Sheath Ureteroneocystostomy of an Injured Ectopic Ureter
Diagnosed in the Acute Post-operative Setting after Robotic Assisted Radical
Prostatectomy.
AB - Radical prostatectomies are one of the most commonly performed operations for the
robotic urologist. When a rare anatomic anomaly leads to an unrecognized
intraoperative injury, standard postoperative management becomes complicated. We
present the case of a patient with an iatrogenic injury to an ectopic ureter that
under went a robotic assisted common sheath ureteroneocystostomy three days post
robotic assisted radical prostatectomy.
PMID- 28702365
TI - Abnormal amyloid beta42 expression and increased oxidative stress in plasma of
CKD patients with cognitive dysfunction: A small scale case control study
comparison with Alzheimer's disease.
AB - BACKGROUND: Cognitive dysfunction has been increasingly recognized in chronic
kidney disease (CKD) patients. Senile plaques are important pathophysiological
characteristic of cognitive dysfunction. The major component of plaques is the
amyloid beta (Abeta) peptide released from proteolytic cleavage of amyloid
precursor protein (APP). Plasma Abeta has been a focus of the growing literature
on blood based biomarkers for cognitive dysfunction. Oxidative stress is
prevalent in CKD and it plays an important role in cognitive dysfunction.
Increased oxidative stress leads to cause cleavage of APP and Abeta production.
The aim of this study is to assess the antioxidant status and Abeta42 levels in
plasma of CKD patients with cognitive dysfunction compared to CKD without
cognitive dysfunction. METHODS: A total of 60 subjects divided into 30 CKD
without cognitive dysfunction and 30 CKD with cognitive dysfunction based on
neuropsychological assessment tests. To compare antioxidant status and Abeta42
levels in plasma, the following groups such as healthy subjects (n = 30),
normocytic normochromic anemia (n = 30) and Alzheimer's disease (AD, n = 10)
patients were also maintained. Plasma Superoxide dismutase (SOD), Catalase (CAT),
Glutathione peroxidase (GPx), Reduced glutathione (GSH) and lipid peroxidation
(LPO) were determined by spectrophotometrically. Abeta level was determined by
immunoblotting method. The parameters were statistically compared with healthy,
normocytic normochromic anemia and AD subjects. RESULTS: Like AD subjects,
significantly increased Abeta and LPO level while decreased SOD, CAT, GPx and GSH
levels were observed in plasma of CKD patients with cognitive dysfunction when
compared to healthy, CKD without cognitive dysfunction and normocytic
normochromic anemic subjects. CONCLUSION: Results suggest that elevated plasma
oxidative stress and Abeta were seen in CKD patients with cognitive dysfunction
may be attributed to pathological changes within the brain.
PMID- 28702366
TI - Methods to determine limit of detection and limit of quantification in
quantitative real-time PCR (qPCR).
AB - Quantitative Real-Time Polymerase Chain Reaction, better known as qPCR, is the
most sensitive and specific technique we have for the detection of nucleic acids.
Even though it has been around for more than 30 years and is preferred in
research applications, it has yet to win broad acceptance in routine practice.
This requires a means to unambiguously assess the performance of specific qPCR
analyses. Here we present methods to determine the limit of detection (LoD) and
the limit of quantification (LoQ) as applicable to qPCR. These are based on
standard statistical methods as recommended by regulatory bodies adapted to qPCR
and complemented with a novel approach to estimate the precision of LoD.
PMID- 28702367
TI - The continuing problem of poor transparency of reporting and use of inappropriate
methods for RT-qPCR.
AB - Attendance at this year's European Calcified Tissue Society's (ECTS) Congress
reveals that the methods used to obtain qPCR results continue to be significantly
flawed and that and their reporting remain inadequate.
PMID- 28702368
TI - How to speed up the polymerase chain reaction.
AB - Reducing the time taken to run qPCR assays on today's qPCR cyclers is rather
straightforward and requires no specialised reagents or instruments. As the first
article in a new series of short technical reports, I demonstrate that it is
possible to reduce significantly both denaturation temperatures and cycling
times, whilst retaining sensitivity and specificity of the original qPCR
conditions.
PMID- 28702369
TI - Mutagenesis of threonine to serine in the active site of Mycobacterium
tuberculosis fructose-1,6-bisphosphatase (Class II) retains partial enzyme
activity.
AB - The glpX gene encodes for the Class II fructose-1,6-bisphosphatase enzyme in
Mycobacterium tuberculosis (Mt), an essential enzyme for pathogenesis. We have
performed site directed mutagenesis to introduce two mutations at residue Thr84,
T84A and T84S, to explore the binding affinity of the substrate and the catalytic
mechanism. The T84A mutant fully abolishes enzyme activity while retaining
substrate binding affinity. In contrast, the T84S mutant retains some activity
having a 10 times reduction in Vmax and exhibited similar sensitivity to lithium
when compared to the wildtype. Homology modeling using the Escherichia coli
enzyme structure suggests that the replacement of the critical nucleophile OH- in
the Thr84 residue of the wildtype of MtFBPase by Ser84 results in subtle
alterations of the position and orientation that reduce the catalytic efficiency.
This mutant could be used to trap reaction intermediates, through
crystallographic methods, facilitating the design of potent inhibitors via
structure-based drug design.
PMID- 28702370
TI - In vitro and in silico characterization of metagenomic soil-derived cellulases
capable of hydrolyzing oil palm empty fruit bunch.
AB - Diversification of raw material for biofuel production is of interest to both
academia and industry. One attractive substrate is a renewable lignocellulosic
material such as oil palm (Elaeis guineensis Jacq.) empty fruit bunch (OPEFB),
which is a byproduct of the palm oil industry. This study aimed to characterize
cellulases active against this substrate. Cellulases with activity against OPEFB
were identified from a metagenomic library obtained from DNA extracted from a
high-Andean forest ecosystem. Our findings show that the highest cellulolytic
activities were obtained at pH and temperature ranges of 4-10 and 30 degrees C
60 degrees C, respectively. Due to the heterogeneous character of the system,
degradation profiles were fitted to a fractal-like kinetic model, evidencing
transport mass transfer limitations. The sequence analysis of the metagenomic
library inserts revealed three glycosyl hydrolase families. Finally, molecular
docking simulations of the cellulases were carried out corroborating possible
exoglucanase and beta-glucosidase activity.
PMID- 28702371
TI - Hydrogen from algal biomass: A review of production process.
AB - Multifariousness of biofuel sources has marked an edge to an imperative energy
issue. Production of hydrogen from microalgae has been gathering much
contemplation right away. But, mercantile production of microalgae biofuels
considering bio-hydrogen is still not practicable because of low biomass
concentration and costly down streaming processes. This review has taken up the
hydrogen production by microalgae. Biofuels are the up and coming alternative to
exhaustible, environmentally and unsafe fossil fuels. Algal biomass has been
considered as an enticing raw material for biofuel production, these days
photobioreactors and open-air systems are being used for hydrogen production from
algal biomass. The formers allow the careful cultivation control whereas the
latter ones are cheaper and simpler. A contemporary, encouraging optimization
access has been included called algal cell immobilization on various matrixes
which has resulted in marked increase in the productivity per volume of a reactor
and addition of the hydrogen-production phase.
PMID- 28702372
TI - Elements for optimizing a one-step enzymatic bio-refinery process of shrimp
cuticles: Focus on enzymatic proteolysis screening.
AB - This article complements an earlier work published in 2015 Baron et al. (2015)
that showed the interest of a shrimp shells bio-refining process. We compare here
the effect of eleven commercial proteases at pH 3.5 or 4.0 on a residual amount
of shrimp shells proteins after 6 h at 50 degrees C. The two pH are obtained
when respectively 40 and 25 mmol of formic acid are added to 5 g of mild dried
shell. Deproteinisation yield above 95% are obtained. Residual amino acids
profile in the solid phase was identical for the eleven proteases except for
pepsin which was similar to the raw material profile. A significant relative
increase in the proportion of Glycine is observed for the ten other cases.
Likewise, shapes of size exclusion chromatograms of the dissolved phase are
similar except with pepsin.
PMID- 28702373
TI - Murine Pancreatic Acinar Cell Carcinoma Growth Kinetics Are Independent of
Dietary Vitamin D Deficiency or Supplementation.
AB - Vitamin D has been proposed as a therapeutic strategy in pancreatic cancer, yet
evidence for an effect of dietary vitamin D on pancreatic cancer is ambiguous,
with conflicting data from human epidemiological and intervention studies. Here,
we tested the role of dietary vitamin D in the in vivo context of the well
characterized Ela1-TAg transgenic mouse model of pancreatic acinar cell
carcinoma. Through longitudinal magnetic resonance imaging of mice under
conditions of either dietary vitamin D deficiency (<5 IU/kg vitamin D) or excess
(76,500 IU/kg vitamin D), compared to control diet (1,500 IU/kg vitamin D), we
measured the effect of variation of dietary vitamin D on tumor kinetics. No
measurable impact of dietary vitamin D was found on pancreatic acinar cell
carcinoma development, growth or mortality, casting further doubt on the already
equivocal data supporting potential therapeutic use in humans. The lack of any
detectable effect of vitamin D, within the physiological range of dietary
deficiency or supplementation, in this model further erodes confidence in vitamin
D as an effective antitumor therapeutic in pancreatic acinar cell carcinoma.
PMID- 28702374
TI - Topical Application of 0.5% Timolol Maleate Hydrogel for the Treatment of
Superficial Infantile Hemangioma.
AB - The therapeutic options for infantile hemangiomas (IHs) have been greatly altered
since the introduction of oral propranolol for successful treatments of IHs.
Recently, there is an increase in the application of topical timolol maleate for
treating superficial IHs. In the present study, we developed a new formulation of
timolol maleate 0.5% hydrogel and treated 321 patients with superficial IHs to
evaluate its efficacy and safety in the treatment of superficial IHs. This new
timolol hydrogel was applied three times daily with a mean duration of 7.1
months. Response to treatment was assessed according to cosmetic improvement by
using visual analog scale (VAS). The average VAS improvement after treatment was
76.4, with 126 patients (39.3%) achieving excellent responses, 159 patients
(49.5%) achieving good responses, 33 patients (10.3%) achieving fair responses,
and three patients (0.9%) achieving poor responses. Age at treatment initiation
(P = 0.0349) and lesion thickness (P = 0.0147) were significantly associated with
therapeutic efficacy. No severe side effects were observed in all patients. In
conclusion, this new topical timolol maleate 0.5% hydrogel appears to be a proper
candidate for treating superficial IHs, and our study provides supportive
evidence and experience of topical timolol maleate in treating superficial IHs.
PMID- 28702375
TI - A Single Nucleotide Polymorphism Is Involved in Regulation of Growth and Spore
Formation of Bacillus anthracis Pasteur II Strain.
AB - Anthrax toxins and capsules, which are encoded by genes located on pXO1 and pXO2,
respectively, are major virulence factors of Bacillus anthracis. Our previous
studies demonstrated that exposure to high-temperatures is unable to abolish the
pXO1 plasmid of the Pasteur II strain, but the growth of the strain was obviously
slower than that of the Sterne strain and wild-type virulent strain. To elucidate
a potential regulatory mechanism of slowing growth, we employed comparative
genome and bioinformatic analysis and revealed a unique SNP (G to T) at the
143135 bp position in pXO1 that is possibly involved in the mediation of growth
of Pasteur II. However, the T to G mutation in groR did not result in any change
of the amino acid sequence. A predominant nucleotide G existed at the 143135 bp
in pXO1 of 100 wild-type B. anthracis isolates and 9 isolates documented in
GenBank, whereas T replaced G in pXO1 of the Pasteur II strain. Further analysis
indicate that the SNP is located in a gene between 143042 and 143173 bp, and that
it encodes a small protein of 43 amino acids and is termed as a growth regulator
(GroR). Site-directed mutagenesis and gene deletion demonstrates that groR
regulates the growth and spore formation of B. anthracis. Our results indicate
that the pXO1 plasmid is involved in the regulation of growth and spore formation
in B. anthracis.
PMID- 28702376
TI - Nematode Species Identification-Current Status, Challenges and Future
Perspectives for Cyathostomins.
AB - Human and animal health is globally affected by a variety of parasitic helminths.
The impact of co-infections and development of anthelmintic resistance requires
improved diagnostic tools, especially for parasitic nematodes e.g., to identify
resistant species or attribute pathological effects to individual species or
particular species combinations. In horses, co-infection with cyathostomins is
rather a rule than an exception with typically 5 to 15 species (out of more than
40 described) per individual host. In cyathostomins, reliable morphological
species differentiation is currently limited to adults and requires highly
specialized expertize while precise morphological identification of eggs and
early stage larvae is impossible. The situation is further complicated by a
questionable validity of some cyathostomins while others might actually represent
cryptic species complexes. Several molecular methods using different target
sequences were established to overcome these limitations. For adult worms, PCR
followed by sequencing of mitochondrial genes or external or internal ribosomal
RNA spacers is suitable to genetically confirm morphological identifications. The
most commonly used method to differentiate eggs or larvae is the reverse-line
blot hybridization assay. However, both methods suffer from the fact that target
sequences are not available for many species or even that GenBank(r) entries are
unreliable regarding the cyathostomin species. Recent advances in proteomic tools
for identification of metazoans including insects and nematodes of the genus
Trichinella will be evaluated for suitability to diagnose cyathostomins. Future
research should focus on the comparative analysis of morphological, molecular and
proteomic data from the same cyathostomin specimen to optimize tools for species
specific identification.
PMID- 28702377
TI - dsRNA Binding Domain of PKR Is Proteolytically Released by Enterovirus A71 to
Facilitate Viral Replication.
AB - Enterovirus 71 (EV-A71) causes hand, foot and mouth disease in young children and
infants, but can also cause severe neurological complications or even death. The
double-stranded RNA (dsRNA)-dependent protein kinase R (PKR), an interferon
induced antiviral protein, phosphorylates the regulatory alpha-subunit of the
eukaryotic translation initiation factor 2 in response to viral infection,
thereby blocking the translation of cellular and viral mRNA and promoting
apoptosis. The cleavage of PKR after infection with poliovirus, a prototype
enterovirus, has been reported by others, but the underlying mechanism of this
cleavage and its role in viral replication remain unclear. In the present study,
we show that viral 3C protease cleaves PKR at a site, Q188, which differs from
the site cleaved during apoptosis, D251. In contrast to the conventional
phosphorylation of PKR by dsRNA, EV-A71 3C physically interacts with PKR to
mediate the phosphorylation of PKR; this effect is dependent on 3C protease
activity. Overexpression of a catalytically inactive PKR mutant (K296H)
accelerates viral protein accumulation and increases virus titer, whereas a K64E
substitution in the dsRNA binding site abolishes this advantage. We also
demonstrate that PKR cleavage mediated by EV-A71 3C protease produces a short N
terminal PKR fragment that can enhance EV-A71 replication, in terms of viral RNA,
viral protein, and viral titers. We conclude that PKR is co-opted by EV-A71 via
viral protease 3C-mediated proteolytic activation to facilitate viral
replication.
PMID- 28702379
TI - RBO achieves international quality levels.
PMID- 28702378
TI - Thioredoxin A Is Essential for Motility and Contributes to Host Infection of
Listeria monocytogenes via Redox Interactions.
AB - Microbes employ the thioredoxin system to defend against oxidative stress and
ensure correct disulfide bonding to maintain protein function. Listeria
monocytogenes has been shown to encode a putative thioredoxin, TrxA, but its
biological roles and underlying mechanisms remain unknown. Here, we showed that
expression of L. monocytogenes TrxA is significantly induced in bacteria treated
with the thiol-specific oxidizing agent, diamide. Deletion of trxA markedly
compromised tolerance of the pathogen to diamide, and mainly impaired early
stages of infection in human intestinal epithelial Caco-2 cells. In addition,
most trxA mutant bacteria were not associated with polymerized actin, and the
rare bacteria that were associated with polymerized actin displayed very short
tails or clouds during infection. Deletion or constitutive overexpression of
TrxA, which was regulated by SigH, severely attenuated the virulence of the
pathogen. Transcriptome analysis of L. monocytogenes revealed over 270 genes that
were differentially transcribed in the DeltatrxA mutant compared to the wild
type, especially for the virulence-associated genes plcA, mpl, hly, actA, and
plcB. Particularly, deletion of TrxA completely reduced LLO expression, and
thereby led to a thoroughly impaired hemolytic activity. Expression of these
virulence factors are positively regulated by the master regulator PrfA that was
found here to use TrxA to maintain its reduced forms for activation.
Interestingly, the trxA deletion mutant completely lacked flagella and was non
motile. We further confirmed that this deficiency is attributable to TrxA in
maintaining the reduced intracellular monomer status of MogR, the key regulator
for flagellar formation, to ensure correct dimerization. In summary, we
demonstrated for the first time that L. monocytogenes thioredoxin A as a vital
cellular reductase is essential for maintaining a highly reducing environment in
the bacterial cytosol, which provides a favorable condition for protein folding
and activation, and therefore contributes to bacterial virulence and motility.
PMID- 28702380
TI - Patient-specific instrumentation in total knee arthroplasty. Should we adopt it?
AB - Total knee arthroplasty (TKA) is a surgical procedure of paramount relevance that
restores a substantial degree of function in arthritic knees. Increased
consideration has been given to the influence of limb alignment on longevity
after TKA, as errors in component placement can be associated with inferior
function and compromised long-term performance. Consequently, numerous studies
comparing patient-specific instrumentation (PSI) to standard instruments (SI)
have been published. Patient-specific approaches use preoperative imaging to
create specific materials for each patient's anatomy and were designed to achieve
a higher rate of success in TKA, causing the entire procedure to be more
efficient and cost-effective. However, it is not clear to what degree these
studies support the potential advantages of PSI. Thus, the present study aimed to
review the current evidence comparing PSI to SI, concerning alignment, cost
effectiveness, and postoperative functional evaluation.
PMID- 28702381
TI - Importance of preclinical evaluation of wear in hip implant designs using
simulator machines.
AB - Total hip arthroplasty (THA) is a surgical procedure that involves the
replacement of the damaged joint of the hip by an artificial device. Despite the
recognized clinical success of hip implants, wear of the articulating surfaces
remains as one of the critical issues influencing performance. Common material
combinations used in hip designs comprise metal-on-polymer (MoP), ceramic-on
polymer (CoP), metal-on-metal (MoM), and ceramic-on-ceramic (CoC). However, when
the design of the hip implant is concerned besides the materials used, several
parameters can influence its wear performance. In this scenario, where the safety
and efficacy for the patient are the main issues, it is fundamental to evaluate
and predict the wear rate of the hip implant design before its use in THA. This
is one of the issues that should be taken into account in the preclinical
evaluation step of the product, in which simulated laboratory tests are
necessary. However, it is fundamental that the applied motions and loads can
reproduce the wear mechanisms physiologically observed in the patient. To
replicate the in vivo angular displacements and loadings, special machines known
as joint simulators are employed. This article focuses on the main
characteristics related to the wear simulation of hip implants using mechanical
simulators, giving information to surgeons, researchers, regulatory bodies, etc.,
about the importance of preclinical wear evaluation. A critical analysis is
performed on the differences in the principles of operation of simulators and
their effects on the final results, and about future trends in wear simulation.
PMID- 28702382
TI - Epidemiology of pelvic ring fractures and injuries.
AB - OBJECTIVE: This study evaluated the pelvic ring fractures and injuries in
patients admitted to and treated at this ward between August, 2012 and January,
2014. METHODS: 66 patients were submitted to treatment protocols according to
their age, gender, skin color, injury mechanism, location of the trauma,
classification of their injuries, emergency intervention, associated injuries,
injured side of the body, treatment, and mortality. The most relevant data were
classified according to statistic procedures, such as Goodman's association test.
Measures were compared with Student's t-test and analysis of variance associated
with Tukey's multiple comparison test. RESULTS: The mean age was 47 years; white
race and male gender were most common. Car or truck accident was the most common
cause of injuries, which occurred mainly in urban sites. Type A injuries were the
most frequent. 16.6% of the cases were submitted to emergency surgery. 42.4%
displayed associated injuries. The right side of the body was the most commonly
affected side. Non-invasive treatment was most commonly used. Death was the
outcome in 3% of the cases, associated to high-energy trauma. CONCLUSIONS: Pelvic
ring fractures and injuries are more often verified among males. In general and
among younger individuals, traffic accidents are the most common cause of the
injury, while among the elderly, ordinary falls are the most commonly verified
cause. The majority of those injuries are suffered in urban areas. Type A
fractures are more frequent. The majority of cases do not require emergency
intervention nor do they feature associated injuries. Non-invasive treatment is
most common and death outcomes are associated to high-energy traumas with severe
injuries.
PMID- 28702383
TI - A retrospective study of titanium elastic stable intramedullary nailing in
displaced mid-shaft clavicle fractures.
AB - OBJECTIVE: The aim of this study is to analyze the functional outcome following
titanium elastic stable intra-medullary nailing (ESIN) for displaced mid-shaft
clavicular fractures (DMCF). METHODS: A retrospective study of 60 patients
between March 2009 and March 2015 was conducted. Patients were selected based on
the inclusion criteria. Six patients were lost during follow up. Out of the
remaining 54 patients, there were 39 males and 15 females. The mean age was 30.6
years. The functional outcome was analyzed using the Constant score, rate of bone
union, complication, and earliest time of return to work. RESULTS: All fractures
united well, with an average time of 7.5 weeks. Follow-up period ranged between
12 months and 18 months (average, 14 months). 24 out of 54 patients had closed
nailing, while 30 had minimal open reduction. The average size of ESIN was 2 mm
(range, 1.5-3 mm). The average Constant score was 97.8 (range, 95-99). There were
no major complications, but minor complications occurred, viz. skin irritation in
15 patients, temporary paresthesia in five patients, and three patients who
developed superficial infections. One case had implant migration and perforation
at the lateral cortex, and one case had delayed union. There were few implant
related problems, as the authors used a standard protocol to remove it after
radiological union. All patients returned to work within 10 weeks of the post
operative period. CONCLUSION: ESIN is a safe, minimally invasive, engenders rapid
healing with good cosmesis, and provides an excellent functional outcome in terms
of patient satisfaction, with fewer complications.
PMID- 28702384
TI - PRWE application in distal radius fracture: comparison and correlation with
established outcomes.
AB - OBJECTIVE: The study aimed to evaluate the correlation between the PRWE score
with other measurements that are already widely used. METHODS: This was a
prospective, cross-sectional, single-center study. Sixty-eight consecutive
patients underwent surgical treatment for distal radius fractures (internal
fixation by locked volar plate or transarticular external fixation). They were
evaluated independently by PRWE, DASH, VAS range of motion, strength, and
radiographic criteria, in one year of follow up. The Mann-Whitney test was used
to compare continuous variables and the Spearman correlation to correlate the
outcomes of interest. RESULTS: PRWE correlated significantly with DASH (p <
0.001) and VAS (p < 0.001). There were no significant correlations with other
outcome measures. CONCLUSION: PRWE presents significant moderate correlation only
with DASH and VAS. Range of motion, strength, and radiographic criteria do not
interfere in the PRWE outcome.
PMID- 28702385
TI - Evaluation of suspected physical abuse in children: a 500-case study.
AB - OBJECTIVE: This study evaluated the epidemiological profile of patients with
suspected physical abuse, especially regarding the occurrence of fractures,
treated in a referral hospital. METHODS: The authors reviewed all reports of
suspected abuse against children and adolescents (AACA) in this hospital from
January 2005 to December 2015. They were assessed and separated by month and
year. The characteristics of the victims of physical abuse with occurrence of
fractures were studied. The features of the fractures were evaluated in those
patients with available radiographs. RESULTS: Of the 3125 notifications, 500 were
classified as physical injuries; of these, 63 had fractures. An annual
progressive increase in notifications was observed. As for age group, 50 patients
(80.6%) were up to three years old and 36 (58%) up to one year. Most were male
(60%) and the likely aggressors were mother alone and both parents (27.5% each).
In 30 patients with available images, fractures of long bones (femur, tibia, and
humerus) predominated (71%), as well as a single fracture line (74%), diaphyseal
location (73%), and a transverse line (57%). There were two deaths in fracture
cases (3%). CONCLUSION: All orthopedists should be alert to suspected AACA in
children with trauma below the age of three, even without classic signs of abuse.
PMID- 28702386
TI - Disorders of the long head of the biceps: tenotomy versus tenodesis.
AB - Disorders of the long head of biceps tendon are common in clinical practice.
Their causes could be degenerative, inflammatory, instability (subluxation or
luxation) or traumatic. They are generally associated to other diseases of the
shoulder, mainly rotator cuff injuries. Currently, there is controversy in the
literature regarding the indications for surgical treatment and the choice of the
best technique for each case, due to the possibility of esthetic deformity, loss
of muscle strength, and residual pain. The objective of this study was to
identify the indications for surgical treatment, the best surgical technique, and
the advantages and disadvantages of each technique described in the orthopedic
literature for the treatment of long head of biceps tendon injuries. A revision
of the orthopedic medical literature on the following databases: Biblioteca
Regional de Medicina (BIREME), Medline, PubMed, Cochrane Library and Google
Scholar, comprising articles published in the period from 1991 to 2015.
PMID- 28702387
TI - Reverse shoulder arthroplasty: clinical results and quality of life evaluation.
AB - OBJECTIVE: To evaluate the clinical and radiological results and the impact on
quality of life of the reverse shoulder arthroplasty. METHODS: Retrospective case
series evaluating 13 patients undergoing reverse shoulder arthroplasty with at
least two years of clinical follow-up. Clinical evaluation was performed before
and after surgery with the ASES and VAS scales and hand-mouth, hand-neck, and
hand-head functional tests. Quality of life was measured with the SF-12
questionnaire. The rate of complications and radiographic postoperative findings
were recorded. RESULTS: The patients improved from 23.1 +/- 15 to 82.7 +/- 15
according to ASES scale (p < 0.001). The physical component of the SF-12
increased from 31.7 +/- 6.9 to 47.1 +/- 8.6 (p < 0.001), while the emotional
increased from 48 +/- 12.3 to 55.5 +/- 7.5 (p = 0.061). The pain reduced from 7.9
to 1 according to the VAS (p = 0.002). The performance on the hand-mouth, hand
neck, and hand-head functional tests showed significant improvement (p = 0.039, p
< 0.001 and p < 0.001, respectively). Complications occurred in 15% of patients
and notching, in 31%. CONCLUSION: Reverse shoulder arthroplasty led to a
significant clinical improvement according to the ASES and VAS scales. The
quality of life has improved according to the physical aspect of the SF-12, and
showed a trend of improvement in the emotional aspect. The complication rate was
15%, and notching occurred in 31%.
PMID- 28702388
TI - In situ repair of partial articular surface lesions of the supraspinatus tendon.
AB - OBJECTIVE: To demonstrate the in situ repair technique of high-degree partial
thickness articular surface lesions of the supraspinatus tendon (SS). The
procedure consists of the arthroscopic surgical repair of these lesions, without
the need to complete the lesion, as occurs in traditional classical technique. A
small incision is made in the longitudinal direction of the intact bursal fibers
and where bone fixation anchors are introduced, which makes the procedure easier.
These anchors are transferred to the tendon and thus enable the repair of the
lesion. METHODS: 48 shoulders were operated in the period 2010-2015. The minimum
follow-up was 12 months and maximum 60 months. Ages ranged from 38 years to 75
years (mean 54 years). They were indicated for the repair of high-degree
symptomatic lesions and at least 30% intact superior bursal fibers of good
quality. RESULTS: Patients were evaluated according to the UCLA criteria, the
results were: 69% excellent, 17% good, 7% fair, and 7% poor. Fair results
occurred in three patients with associated symptoms of polyarthralgia who
remained with residual pain. Three patients developed postoperative joint
stiffness (7%). CONCLUSION: The procedure under study is safe and easy to
reproduce. It shows high rates of positive results (86%). The opening made in the
bursal side of the SS tendon allowed the arthroscope to remain in the subacromial
space, making it easier to perform surgery.
PMID- 28702389
TI - Correlation between the elbow flexion and the hand and wrist flexion after
neurotization of the fascicles of the ulnar nerve to the motor branch to the
biceps.
AB - OBJECTIVE: Gain in elbow flexion in patients with brachial plexus injury is
extremely important. The transfer of a fascicle from the ulnar nerve to the motor
branch of the musculocutaneous nerve (Oberlin surgery) is a treatment option.
However, in some patients, gain in elbow flexion is associated with wrist and
finger flexion. This study aimed to assess the frequency of this association and
the functional behavior of the limb. METHODS: Case-control study of 18 patients
who underwent the Oberlin surgery. Group 1 included patients without
disassociation of range of elbow flexion and that of the fingers and wrist; Group
2 included patients in whom this disassociation was present. In the functional
evaluation, the Sollerman and DASH tests were used. RESULTS: It was observed that
38.89% of the patients did not present disassociation of elbow flexion with
flexion of the wrist and fingers. Despite the existence of a favorable difference
in the group with disassociation of the movement, when the Sollerman protocol was
applied to the comparison between both groups, this difference was not
statistically significant. With the DASH test, however, there was a statistically
significant difference in favor of the group of patients who managed to
disassociate the movement. CONCLUSION: The association of elbow flexion with
flexion of the wrist and fingers, in the group studied, was shown to be a
frequent event, which influenced the functional result of the affected limb.
PMID- 28702390
TI - Percutaneous golfer's elbow release under local anesthesia: a prospective study.
AB - OBJECTIVES: To evaluate the results of percutaneous golfer's elbow release under
local anesthesia. METHODS: From December 2010 to December 2013, 34 elbows in 34
patients (10 males and 24 females) that presented golfer's elbow for over one
year were recruited from the outpatient department. All patients were operated
under local anesthesia and were followed-up for 12 months. The functional outcome
was evaluated through the Mayo Elbow Performance Index (MEPI). RESULTS: Pain
relief was achieved on average eight weeks after surgery. The results were
excellent in 88.23% (30/34) cases and good in 11.76% (4/34) cases. Neither wound
related complications nor ulnar nerve complications were observed. On subjective
evaluations, 88.23% (30/34) patients reported full satisfaction and 11.76% (4/34)
patients reported partial satisfaction with the results of treatment. CONCLUSION:
Percutaneous golfer's elbow release under local anesthesia is a minimally
invasive procedure that can be performed in an outpatient setting. This procedure
is easy, quick, and economical, presenting a low complication rate with good
results.
PMID- 28702391
TI - Comparative evaluation of the results of three techniques in the reconstruction
of the anterior cruciate ligament, with a minimum follow-up of two years.
AB - OBJECTIVE: To compare the clinical results of the reconstruction of the anterior
cruciate ligament by transtibial, transportal, and outside-in techniques.
METHODS: This was a retrospective study on 90 patients (ACL reconstruction with
autologous flexor tendons) operated between August 2009 and June 2012, by the
medial transportal (30), transtibial (30), and "outside-in" (30) techniques. The
following parameters were assessed: objective and subjective IKDC, Lysholm,
KT1000, Lachman test, Pivot-Shift and anterior drawer test. RESULTS: On physical
examination, the Lachman test and Pivot-Shift indicated a slight superiority of
the outside-in technique, but without statistical significance (p = 0.132 and p =
0.186 respectively). The anterior drawer, KT1000, subjective IKDC, Lysholm, and
objective IKDC tests showed similar results in the groups studied. A higher
number of complications were observed in the medial transportal technique (p =
0.033). CONCLUSION: There were no statistically significant differences in the
clinical results of patients undergoing reconstruction of the anterior cruciate
ligament by transtibial, medial transportal, and outside-in techniques.
PMID- 28702392
TI - Subchondroplasty for treating bone marrow lesions in the knee - initial
experience.
AB - OBJECTIVE: To evaluate the use of subchondroplasty in the treatment of bone
marrow lesions in an initial series of five cases. METHODS: The study included
patients aged between 40 and 75 years old, with pain in the knee for at least six
months, associated with high-signal MRI lesion on T2 sequences, on the tibia or
femur. Patients were assessed using the visual analog pain scale and the KOOS
score, one week before surgery and one, three, six, 12, and 24 weeks after the
procedure. Subchondroplasty was performed with a technique developed for filling
the area of the bone marrow lesion with a calcium phosphate bone substitute.
RESULTS: The filling was performed on the medial femoral condyle in four patients
and medial tibial plateau in one case. The assessment by the KOOS score presented
a preoperative average of 38.44 points and 62.7, 58.08, 57.92, 63.34, and 71.26
points with one, three, six, 12, and 24 weeks after surgery, respectively. In the
evaluation by the VAS, the average was 7.8 points preoperatively and 2.8, 3, 2.8,
1.8, and 0.6 points over the same periods. All patients were able to ambulate
without additional support, on the first day after the procedure. One patient had
a minimal graft dislocation to the soft tissue, with local pain, which resolved
completely after a week. CONCLUSION: The subchondroplasty technique provided
significant improvements in the parameters of pain and functional capacity in the
short-term assessment.
PMID- 28702393
TI - The arcade of Struthers: an anatomical study and clinical implications.
AB - OBJECTIVE: To determine the frequency and features of the arcade of Struthers,
and to assess its clinical implication in ulnar nerve compression. METHOD: Forty
arms from 26 cadaver specimens were dissected in the Anatomy Laboratory of this
institution. The extension of the arcade, distance from the medial epicondyle,
and relation with ulnar nerve were recorded. RESULTS: The arcade of Struthers was
identified in 40 dissected arms (100%). In 29 (72.5%) the ulnar nerve was covered
by a muscular arcade, in nine (22.5%) by an aponeurotic arcade, and in two (5%)
the arcade was beneath the ulnar nerve. The extension of the arcade ranged from
3.0 to 7.5 cm, and the distance from the medial epicondyle ranged from 2.5 to 7.0
cm. CONCLUSION: The arcade of Struthers is a musculoaponeurotic canal that
represents an important site of entrapment or compression of the ulnar nerve. The
arcade, the intermuscular septum, and the internal brachial ligament should be
released in patients submitted to ulnar nerve anterior transposition surgery.
PMID- 28702394
TI - Osteoid osteoma - radiofrequency ablation treatment guided by computed
tomography: a case series.
AB - The osteoid osteoma is a benign primary bone tumor that affects mainly males in
the second and third decades of life. Radiographic findings show a radiolucent
nidus surrounded by reactive sclerotic bone, particularly in the long bones of
the lower extremity. Clinically, it presents persistent pain, which is worse at
night and improves with salicylates. It can be a self-limiting injury, with an
average duration of three years, but because of pain intensity and intolerance to
prolonged use of nonsteroidal anti-inflammatories, surgical treatment is an
option. The diagnosis is suspected according to the history and radiographic
findings, and the confirmation is made by histological analysis. The traditional
surgical treatment is the complete excision of the nidus, but some disadvantages
have been described, such as difficulties in localizing the lesion and risk of
fracture during the procedure, hospital stay for pain control, and unfavorable
esthetic outcome. The authors report a series of cases treated with thermal
radiofrequency ablation guided by computed tomography in this service. It is a
safe and an effective percutaneous method that aims to cure, minimizing the
trauma and morbidity when compared with the conventional block-resection method.
PMID- 28702395
TI - Anatomical and radiological characteristics in adolescent idiopathic scoliosis
with surgical indication.
AB - OBJECTIVE: This study aims to analyze the anatomical and radiological
characteristics of adolescent idiopathic scoliosis patients with surgical
indication. METHODS: Retrospective, descriptive study of 100 medical records
pertaining to patients included in the group of scoliosis with surgical
indication from the years 2008 to 2015. Descriptive statistics were used for
statistical analysis. RESULTS: 28 patients met the inclusion and exclusion
criteria, and were selected for the study. The average age was 15.4 (SD +/- 1.2
years); in the selected sample, the female/male ratio was 6:1; the kyphosis
measured in degrees by Cobb angle between T5-T12 had an average 32.10 (SD +/-
13.37); according to the Lenke classification, the most prevalent type was type
2, representing 28.6% of cases. CONCLUSION: The mean patient age in the present
study was 15.4 (SD +/- 1.2 years); the most prevalent type was type 2 in the
Lenke classification. There is a need for new anatomical and radiological studies
to elucidate the morphological characteristics common in adolescent idiopathic
scoliosis patients.
PMID- 28702396
TI - Can ethanol be used as an adjuvant to extended curettage in order to reduce the
recurrence rate of aneurysmal bone cyst?
AB - OBJECTIVE: The best treatment of aneurysmal bone cyst (ABC) is still unclear.
This study aimed to evaluate the usefulness of extended curettage and ethanol as
an adjuvant to reduce local recurrence of ABCs. METHODS: Retrospectively, 68
cases treated for primary and secondary ABCs caused by benign tumors from 2003 to
2013 were enrolled to a follow-up visit between one to ten years after the
surgery. The treatment protocol was en-bloc resection, biopsy and curettage,
extended curettage consisted of curettage, high-speed burring, ethanol 96%, and
electrocauterization (combined four-step alcohol-using approach) followed by
defect filling, consecutively. RESULTS: Among 36 patients with primary ABCs (16
male, 20 female, mean age of 16 years, range 3-46 years), 29 cases were treated
with the combined four-step alcohol-using approach, four patients with resection,
and three with biopsy and curettage. Thirty-two cases had secondary ABCs on
benign lesions (17 male, 15 female). The recurrence rate was 5.88 in all primary
and secondary ABC cases; two recurrences among 29 patients with primary ABCs
(6.9%) and one recurrence among the 22 cases with secondary ABCs (4.5%).
CONCLUSIONS: It could be suggested that the combined four-step alcohol-using
approach may result in a very low recurrence rate of primary and secondary ABC
lesions.
PMID- 28702397
TI - Reconstruction of the distal biceps tendon using triceps graft: a technical note.
AB - Rupture of the distal biceps brachii tendon typically occur in a contraction
against resistance with the elbow in 90 degrees of flexion. Chronic ruptures are
uncommon and are complicated by tendon and muscle retraction and poor quality.
Some reconstruction techniques have been described in the literature, with
variations on the surgical exposures, type of graft (allo or autograft), graft
donor site, and type of attachment to the radial tuberosity. The authors report
the case of a patient presented a rupture of the distal biceps brachii tendon
that took place five weeks earlier and, therefore, underwent reconstruction using
autograft from the central strip of triceps tendon through double incision and
fixation with anchors to the radial tuberosity. The use of the triceps brachii as
autograft for reconstruction of chronic ruptures of the distal biceps had not yet
been described in the literature. The authors have chosen to use it due to its
biomechanical characteristics that qualify it as suitable for this procedure and
because this is easier for collection, using the same operating field at the same
joint, minimizing the negative effects of the donor area. After six months
postoperatively, the patient has full movement arc and restoration of 96% of the
flexion strength and 90% of the supination strength when compared with the
contralateral limb. This procedure appears to be a good option for cases of
chronic distal biceps rupture in older patients who have functional demand of
supination.
PMID- 28702398
TI - Late screw perforation of external iliac artery following acetabular revision. A
simple solution for a rare complication.
AB - Vascular lesions, although quite rare, are one of the most devastating
complications in the context of a hip prosthesis. Therefore, the correct
diagnosis is crucial to prevent irreversible damage to the patient. The authors
present the case of a 70-year-old Caucasian woman with an ischemic lower limb as
consequence of a late perforation of external iliac artery due to an acetabular
screw. The issue was resolved by simply cutting part of the screw, avoiding other
surgical options that would be much more aggressive for the patient. Careful
clinical evaluation allowed for a correct diagnosis and a timely creative
treatment, preventing further consequences to the patient.
PMID- 28702399
TI - Bilateral simultaneous neck femur fracture following domestic fall in an elderly
patient: a rare case report.
AB - Simultaneous bilateral neck femur fracture is a rare entity that has been
associated with underlying bone disease, various metabolic diseases, high-energy
trauma, and seizure disorders. Its occurrence following minimal trauma is very
rare. This article presents the case of a 66-year-old female who sustained
bilateral intracapsular fracture neck femur following a slip and fall at home.
Single-stage bilateral cemented total hip replacement was done using a direct
lateral approach with alternate right and left lateral positions. The authors
report a satisfactory outcome, with Harris hip score of 98 at one year, which
persisted until her last follow-up at 30 months.
PMID- 28702400
TI - Sarcomatous transformation of a hemosiderotic fibrohistiocytic lipomatous tumor:
a case report.
AB - Hemosiderotic fibrohistiocytic lipomatous tumors are rare neoplasms that were
first described in 2000. Initially considered a benign lipotamous lesion of the
soft tissues, nowadays they are considered to be a locally aggressive tumor. They
occur mainly in the foot and ankle of women in their fifth and sixth decades,
although they may be found in any place in the lower limbs and, more rarely, in
other parts of the body. Histologically, hemosiderotic fibrohistiocytic
lipomatous tumors consist of a mixture of mature adipose tissue, fusiform cell
fascicles, macrophages that often contain cytoplasmic hemosiderin, mononuclear
inflammatory infiltrate, and stroma that may be focally myxoid. Local recurrence
is observed in nearly one-third of all cases. There is no consensus in the
literature whether this tumor is a part of a spectrum that comprises pleomorphic
hyalinizing angiectatic tumors and myxoinflammatory fibroblastic malignant
tumors, or if it is an independent entity. The authors report a case of a
neoplasia after a diagnosis of a hemosiderotic fibrohistiocytic lipomatous tumor
in a 38-year-old woman, with two recurrences and later sarcomatous
transformation. An immunohistochemical study indicated myofibroblastic
differentiation of a malignant neoplasm. To the best of the authors' knowledge,
there are only few reported cases of malignant transformation in hemosiderotic
fibrohistiocytic lipomatous tumors.
PMID- 28702401
TI - Outcome of HER2 Testing by FISH applying ASCO/CAP 2007 and 2013 guideline in IHC
equivocal group of breast cancer: Experience at tertiary cancer care centre.
AB - BACKGROUND AND OBJECTIVES: HER2 testing guideline of ASCO/CAP for interpretation
and reporting has recently been revised. The study is aimed to measure the impact
of 2013 CAP guideline on equivocal HER2 test outcome (immunohistochemistry [IHC]
2+) when tested by fluorescent in situ hybridization (FISH). The study also aims
at finding the frequency of polysomy and monosomy of chromosome 17. MATERIALS AND
METHODS: Specimens were collected in Rajiv Gandhi Cancer Institute and Research
Centre, New Delhi, India. IHC was performed in every case, and FISH was performed
in IHC2+ cases. RESULTS: In final analysis includes 557 subjects on the basis of
CAP guideline 2007 and CAP guideline 2013. One hundred ninety-two subjects
(34.4%) were HER2 amplified according to CAP scoring 2007, and 246 subjects (44%)
according to 2013 CAP scoring. CONCLUSIONS: FISH results were evaluated (IHC2 +
interpreted according to CAP 2007 guideline) with both 2007 and 2013 ASCO/CAP
scoring criteria, we identified significantly more HER2 positive cases as
compared to cases evaluated using the 2007 criteria (P < 0.05). We also found
that in breast carcinoma, HER2 status in the presence of polysomy 17 may vary
with the scoring criteria used. Evaluation of FISH result using 2013 ASCO/CAP
criteria means that more patients with breast cancer may be appropriate for
targeted treatment with trastuzumab, potentially improving their outcome.
PMID- 28702402
TI - In the era of next generation sequencing, is the cytogenetic analysis still
important in polycythemia vera?
PMID- 28702403
TI - Efficacy and safety of short course adjuvant trastuzumab combination chemotherapy
in breast cancer.
AB - BACKGROUND: The adjuvant short course 9-week trastuzumab combination therapy for
human epidermal receptor 2 positive breast cancer patients may often be
considered as a cost-effective and safe option and has important implications for
the Indian subcontinent as well as other developing countries. However, such
regimens of shorter duration trastuzumab therapy like FinHer, offered in view of
economic constraints, may not be able to achieve globally comparable cure rates
in early breast cancer especially with high-risk women with more than 3 lymph
node positive. METHODS AND MATERIAL: Outcome of 21 patients with HER2 positive
breast cancer was treated with short course trastuzumab combination chemotherapy
in the adjuvant setting was studied. RESULTS: Out of 21 patients 15 are alive and
disease free with a follow up of up to 73 months (median follow up 42 months).
PMID- 28702404
TI - Breast cancer in young women: A retrospective study from tertiary care center of
north India.
AB - AIM: Breast cancer is the most common cause of cancer in women worldwide. They
have more aggressive clinical behaviour with poor outcomes in younger patients.
The aim of this study was to evaluate the impact of age on prognosis of breast
cancer in women above and under 40 years of age. MATERIAL AND METHODS: Medical
record of 415 patients with invasive breast cancer were analysed from January
2011 to December 2014 in our department. The last was done in December 2015. All
cases diagnosed with breast cancer stages I to IV were evaluated, and grouped on
the basis of age [less than 40 and above 40 years]. Baseline categorical
variables were analysed using the Chi-square test or Fisher's exact test. Non
categorical variable were analysed using t-test. RESULT: A total of 372 patients
were reviewed because 42 patients defaulted. The median age at the time of
diagnosis was 44.6 years (range 23 to 90 years). Metastasis to distant organs
were more in women with age <40. Tumour relapse occurred in 131 cases, among
which 84 cases died, 35 patients (26.31%) in less than 40 group vs. 49 patients
(20.50%) in above 40 groups. The estimated median OS in the two groups are 32 and
41 months respectively. CONCLUSION: The biological behaviour of breast cancer in
younger age group has been shown to be associated with aggressive nature and has
a worse clinical outcome as compared to that in older group.
PMID- 28702405
TI - The impact of irradiation dose on the computed tomography radiographic response
of metastatic nodes and clinical outcomes in cervix cancer in a low-resource
setting.
AB - INTRODUCTION: The aim of this study is to investigate the relationship between
the radiation dose to pelvic and para-aortic lymph nodes, nodal response, and
clinical outcomes in a resource-poor setting based on computed tomography (CT)
nodal size alone. MATERIALS AND METHODS: This retrospective study from 2009 to
2015 included 46 cervical cancer patients with 133 metastatic pelvic and para
aortic lymph nodes definitively treated with chemoradiation and brachytherapy in
a public hospital with limited access to positron emission tomography (PET)
scans. Hence, short axis of the lymph node on CT scan was used as a measure of
metastatic nodal disease, before and following radiation therapy. Inclusion
criteria required the pelvic and para-aortic nodes to have the shortest axis
diameter on CT scan of >=8 mm and >=10 mm, respectively. Based on PET resolution,
a node that decreased to half of its inclusion cutoff size was considered to have
a complete response (CR). Relevant clinical outcomes were documented and
correlated with nodal features, nodal radiation doses, and treatment
characteristics. RESULTS: After controlling for other predictive factors,
increased nodal dose was associated with increased probability of CR per study
definition (P = 0.005). However, there was no statistically significant
association between dose and pelvic/para-aortic, distant and total recurrence
(TR), and any recurrence at any location (P = 0.263, 0.785, 1.00, respectively).
Patients who had no CR nodes had shorter pelvic/para-aortic recurrence-free
survival (PPRFS) and TR-free survival (TRFS) than patients who had at least one
CR node (P = 0.027 and 0.046, respectively). Patients with no CR nodes also had
shorter PPRFS than patients who had all nodes completely respond (P < 0.05).
CONCLUSIONS: Using CT-based measures, we found that increased nodal dose is
associated with an increased probability of CR (as defined) and nodal CR is
associated with increased PPRFS and TRFS. We were unable to determine the cutoff
dose required for a CR.
PMID- 28702406
TI - Epithelioid angiosarcoma: 10 years postrenal transplant.
PMID- 28702407
TI - 18F-fluorodeoxyglucose positron emission tomography-computed tomography scan
after gastric endoscopy in those who present with non-specific symptoms, is it
necessary or not?
AB - BACKGROUND AND AIMS: Retrospectively analyze the sensitivity of 18F
fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET
CT) in the diagnosis of gastric malignancy compared with gastric endoscopy in
persons with nonspecific symptoms and evaluate the necessity of 18F-FDG PET-CT
scan before surgery. MATERIALS AND METHODS: A total of 53 patients with gastric
malignancy proven by surgery and pathology were enrolled in the study. All the
patients underwent gastric endoscopy and PET-CT scan before surgery. And the PET
CT images were interpreted by the observers who were blinded to the results of
the gastric endoscopy. The sensitivity of gastric endoscopy, 18F-FDG PET-CT, and
serum tumor markers in the diagnosis of gastric malignancy were calculated
ultimately. RESULTS: Of 53 gastric malignancy patients, five cases were proven to
be false-negative detected by gastric endoscopy, and the sensitivity of which was
90.57%. The sensitivity of PET scan alone was 86.79%, which was observed no
significant difference to that of gastric endoscopy diagnosis, P = 0.54. While
all of the patients had been detected positive on PET-CT images, the sensitivity
of which was significantly higher than that of the gastric endoscopy diagnosis or
that of the serum tumor markers, P < 0.001. And the FDG uptake was positively
correlated with the depth of the cancer invasion into the gastric wall (P <
0.0001) and the degree of lymph nodes infiltration (P = 0.02). It also various
from different differentiation degree significantly, P = 0.04. CONCLUSIONS: 18F
fluorodeoxyglucose PET-CT could detect gastric carcinoma in persons with
nonspecific symptoms which showed negative in gastric endoscopy. And it is
necessary to be aware of the possibility of gastric malignancy when the result of
PET-CT scan is positive.
PMID- 28702408
TI - Verrucous carcinoma of foot at an unusual site: Lessons to be learnt.
PMID- 28702409
TI - Phase IIb trial comparing two concurrent cisplatin schedules in locally advanced
head and neck cancer.
AB - BACKGROUND: Concurrent chemoradiation with 3 weekly cisplatin (100 mg/m2) is the
standard of care for locally advanced head and neck cancer. However, this regimen
has been shown to be associated with lesser compliance and higher toxicities.
Hence, there is a need to explore alternative concurrent cisplatin regimens.
OBJECTIVES: The objective of this study was to compare the efficacy and
toxicities of 3 weekly cisplatin (100 mg/m2) with weekly cisplatin (40 mg/m2)
concurrently with radiation in patients with locally advanced head and neck
cancer. PATIENTS AND METHODS: This phase IIb trial randomized 56 patients with
Stage III and IV squamous cell carcinoma of oropharynx, hypopharynx, and larynx
to Arm A or Arm B. Arm A received cisplatin 100 mg/m2 3 weekly and Arm B received
cisplatin 40 mg/m2 weekly concurrently with radiation. The primary end point was
disease-free survival (DFS) and secondary end points were overall survival (OS)
and acute toxicity. DFS and OS were estimated using Kaplan-Meier method, and log
rank test was used to assess the difference in these distributions with respect
to treatment. RESULTS: The 2-year DFS in Arm A and Arm B was 64.5% and 52.8%,
respectively (P = 0.67). The OS at 2 years was 71% and 61.1% in Arm A and Arm B,
respectively (P = 0.61). There were no significant differences in acute
hematological, renal, or mucosal toxicities between the two arms. CONCLUSION:
This study showed a nonsignificant improvement in DFS and OS in the 3 weekly
cisplatin arm over the weekly arm with comparable toxicities. The trial is
registered with Clinical Trial Registry of India (CTRI registration number:
CTRI/2013/05/003703, URL-http://ctri.nic.in).
PMID- 28702410
TI - Plasmablastic lymphoma in immunocompetent and in immunocompromised patients:
Experience at a regional cancer centre in India.
AB - INTRODUCTION: Plasmablastic lymphoma (PBL) is a rare lymphoma associated with
immunosuppression. It is strongly associated with immunosuppression (human
immunodeficiency virus [HIV]) and often occurs within the oral cavity. PBL is
also seen in patients receiving immunosuppressive therapy; however, despite its
predisposition for the immunocompromised patients, PBL has been diagnosed in
immunocompetent patients. AIM: This study aims to prognostic factors and outcome
of PBL in immunocompromised and in immunocompetent patients. MATERIALS AND
METHODS: We conducted a retrospective study at our institute from the year 2008
to 2015. RESULTS: A total of 13 patients (8 males and 5 females) with PBL were
identified. Eight patients (61.5%) had extraoral PBL (median age 30.2 years) and
5 patients (38.5%) had oral PBL (median age 44 years). Most common extraoral site
was gastrointestinal tract. Eight (61.5%) out of 13 patients were HIV positive.
More than 50% of patients had Ann Arbor Stage III or IV. All the cases were CD20
negative and CD138 positive. Seven out of 13 patients had Ki-67 more than 80%.
Nine patients received cyclophosphamide, doxorubicin, vincristine, and prednisone
chemotherapy. Three patients were on best supportive care due to poor performance
status (PS). One patient received intensive chemotherapy with CODOX-M/IVAC. The
median overall survival was 9 months in HIV-positive patients and 6 months in HIV
negative patients. The prognosis was worse in patients with Ki-67 of >80%.
STATISTICAL ANALYSIS: Survival curves were generated using the Kaplan-Meier
method and analyzed using log-rank test and Fisher's t-test. CONCLUSION: The
present study confirms that PBL in both HIV-positive and in HIV-negative patients
has an overall unfavorable outcome. The most important prognostic factors are
stage, ki-67, and the Eastern Cooperative Oncology Group PS of the patient at the
time of presentation.
PMID- 28702411
TI - Diffuse large B-cell lymphoma in elderly: Experience from a tertiary care
oncology center in South India.
AB - INTRODUCTION: Diffuse large B-cell lymphoma (DLBCL) is the most frequent non
Hodgkins lymphoma in the elderly. With the rising proportion of older persons in
India, it is important to study current patterns and management of this disease,
given that data in this regard are scarce in Indian settings. The aim of this
study was to document the clinical features of DLBCL among elderly patients and
their outcome over 7 years at a tertiary care oncology center. MATERIALS AND
METHODS: This was a retrospective records review of 119 DLBCL cases between
January 2007 and January 2015 aged 60 years and above done at Kidwai Memorial
Institute of Oncology, Bengaluru, Karnataka, India. Clinical staging was done
according to Ann Arbor staging as modified by Cotswold's and International
Prognostic Index (IPI) calculated. RESULTS: The mean age was 69.54 years (+/
5.44) with male: female ratio of 1.52:1. B symptoms were seen in 33% of patients.
Thirty-six percent of the patients had stage II disease. The advanced stage was
seen in 12% and bulky disease in 9.5%. Bone marrow was involved in 12%. The most
common extranodal site was the head and neck region. The distribution according
to the IPI was as follows: Low risk 38 (31.93%), low-intermediate risk 53
(44.54%), high-intermediate risk 20 (16.80%), and high risk 8 (6.72%). Among 119
patients, 98 (64.7%) received treatment with either combination of rituximab,
cyclophosphamide, adriamycin, vincristine, epirubicin, and prednisolone. Overall
response rate was 63.26% with a complete response rate of 38.77%. The overall
survival ranged from 2 to 123 months with the median being 9.5 months.
CONCLUSION: In elderly, DLBCL is common in seventh decade and most of them
present in an early stage and low IPI. The incorporation of rituximab to
anthracycline based chemotherapy shows a significant improvement in survival in
elderly DLBCL.
PMID- 28702412
TI - Megakaryocytic morphology in Janus kinase 2 V617F positive myeloproliferative
neoplasm.
AB - CONTEXT: Alterations in megakaryocyte morphology are the hallmark of
myeloproliferative neoplasms (MPNs). These neoplasm are also associated with
Janus kinase 2 (JAK2) V617F mutation in nearly 95% patients with polycythemia
vera (PV), 40% patients of essential thrombocythemia (ET) and 50% patients of
myelofibrosis (MF). The utility of megakaryocyte morphology in these disorders in
correlation with JAK2 V617F remains unresolved. AIMS: The aim of the study was to
assess the morphology of megakaryocytes in bone marrow aspirates (BMAs) and bone
marrow biopsies of patients of BCR-ABL negative MPNs with JAK2 V617F mutation.
SETTINGS AND DESIGN: This study was a retrospective and prospective, hospital
based study undertaken for a period ranging from January 2011 to April 2015.
SUBJECTS AND METHODS: Assessment of morphological features of megakaryocytes in
15 BMAs and their respective biopsies which included seven cases of PV, three
cases of ET, and five cases of MF with JAK2 V617F mutation. STATISTICAL ANALYSIS
USED: Chi-square test and Fisher exact test were used to compare the different
features of megakaryocytes. Software version SPSS 13.0 was used. RESULTS:
Megakaryocytes in ET were found to have characteristically large size with
staghorn multinucleated nuclei and exhibiting large amount of cytoplasm. MF
showed dense clustering of megakaryocytes with staghorn nucleus along with
sinusoidal dilatation and intrasinusoidal hematopoiesis. PV showed loose and
dense clustering of megakaryocytes with a predominance of cloud-like nuclei. Few
of the megakaryocytic morphologic features showed overlap between MF and PV and
between ET and early MF. CONCLUSIONS: Megakaryocytic morphology can aid in the
accurate diagnosis of the different subcategories of MPNs. This would help in
categorization of clinically suspicious patients of JAK2 V617F negative patients.
PMID- 28702413
TI - Presentation of mucinous adenocarcinoma of renal pelvis masquerading as gross
hydronephrosis: A histopathological surprise.
PMID- 28702414
TI - An observational study on safety and efficacy of povidone-iodine for pleurodesis
in cancer patients.
AB - INTRODUCTION: Pleurodesis is a time-honored procedure for malignant effusion as
one of the palliative procedures to treat recurrent effusions. Various agents
have been used in the past such as tetracycline, talc, bleomycin, and povidone
iodine. This paper aims at evaluating safety and efficacy of povidone-iodine for
the procedure. MATERIALS AND METHODS: One hundred and four patients underwent of
pleurodesis with povidone-iodine done at our center for malignant effusion
between June 2008 and August 2015. The safety and efficacy of the procedure was
analyzed. RESULTS: One hundred and four patients of malignant effusion with mean
age of 53 years and a mean follow-up of 7.8 months were evaluated. A total of 79%
patients did not show any reaccumulation of fluid in their follow-up. There was
no periprocedural mortality. Eight patients had severe pain; eleven patients had
fever, while one patient had arrhythmia. CONCLUSION: Povidone-iodine is a simple,
cheap, and effective method of pleurodesis with no major complication and a high
success rate.
PMID- 28702415
TI - Impact and prognostic value of 18F-fluorodeoxyglucose positron emission
tomography-computed tomography scan in the evaluation of residual head and neck
cancer: Single-center experience from Pakistan.
AB - BACKGROUND: Overview of clinical impact of positron emission tomography-computed
tomography (PET-CT) scans in patients with head and neck carcinomas at our
center. METHODS: Retrospective review of posttreatment 18F-fluorodeoxyglucose
(18F-FDG) PET-CT scans in patients with head and neck carcinomas with risk of
residual disease. Clinical outcome served as the reference standard. RESULTS:
This study included 93 patients (65.6% males, mean age: 48.8 years +/- 17.2
standard deviation) with squamous cell carcinoma as most frequent histopathology
(91.4%). PET-CT scans were performed on average 6 months posttreatment.
Diagnostic accuracy, positive predictive value, and negative predictive value of
PET-CT for disease were found to be 88%, 88%, and 92%, respectively. A median
follow-up of 24 months was available for 91 patients. Kaplan-Meier curves showed
significantly higher disease-free survival with negative PET-CT as compared to
positive PET-CT (P = 0.01) and maximum standardized uptake values of <5.0 (P =
0.01). CONCLUSION: FDG PET-CT has diagnostic and prognostic implications in
treated patient of head and neck cancers.
PMID- 28702416
TI - Carotid blowout syndrome: An oncological emergency less discussed.
PMID- 28702417
TI - Folfox encephalopathy: A rare case series.
PMID- 28702418
TI - Long-term survival following repeat liver resections in metastatic ovarian
granulosa cell tumor: Case report with review of the literature.
PMID- 28702419
TI - Scoring criteria for the evaluation of micronuclei in oral exfoliated cells.
PMID- 28702420
TI - Complete response with crizotinib in two children with chemotherapy resistant
neuroblastoma.
PMID- 28702421
TI - Estimation of cancer risk due to exposure to lead contamination in Joss paper.
PMID- 28702422
TI - Carcinomatous meningitis as first sign of relapse in a patient with gastric
Adenocarcinoma: A rare presentation.
PMID- 28702423
TI - Food Ingredients That Inhibit Cholesterol Absorption.
AB - Cholesterol is a vital component of the human body. It stabilizes cell membranes
and is the precursor of bile acids, vitamin D and steroid hormones. However,
cholesterol accumulation in the bloodstream (hypercholesterolemia) can cause
atherosclerotic plaques within artery walls, leading to heart attacks and
strokes. The efficiency of cholesterol absorption in the small intestine is of
great interest because human and animal studies have linked cholesterol
absorption with plasma concentration of total and low density lipoprotein
cholesterol. Cholesterol absorption is highly regulated and influenced by
particular compounds in the food supply. Therefore, it is desirable to learn more
about natural food components that inhibit cholesterol absorption so that food
ingredients and dietary supplements can be developed for consumers who wish to
manage their plasma cholesterol levels by non-pharmacological means. Food
components thus far identified as inhibitors of cholesterol absorption include
phytosterols, soluble fibers, phospholipids, and stearic acid.
PMID- 28702424
TI - Epigenetics: Linking Nutrition to Molecular Mechanisms in Aging.
AB - Healthy aging has become a major goal of public health. Many studies have
provided evidence and theories to explain molecular mechanisms of the aging
process. Recent studies suggest that epigenetic mechanisms are responsible for
life span and the progression of aging. Epigenetics is a fascinating field of
molecular biology, which studies heritable modifications of DNA and histones that
regulate gene expression without altering the DNA sequence. DNA methylation is a
major epigenetic mark that shows progressive changes during aging. Recent studies
have investigated aging-related DNA methylation as a biomarker that predicts
cellular age. Interestingly, growing evidence proposes that nutrients play a
crucial role in the regulation of epigenetic modifiers. Because various nutrients
and their metabolites function as substrates or cofactors for epigenetic
modifiers, nutrition can modulate or reverse epigenetic marks in the genome as
well as expression patterns. Here, we will review the results on aging-associated
epigenetic modifications and the possible mechanisms by which nutrition,
including nutrient availability and bioactive compounds, regulate epigenetic
changes and affect aging physiology.
PMID- 28702425
TI - Differential Effects of Cod Proteins and Tuna Proteins on Serum and Liver Lipid
Profiles in Rats Fed Non-Cholesterol- and Cholesterol-Containing Diets.
AB - Fish muscles are classified into white and red muscles, and the chemical
composition of the two fish muscles have many differences. Few reports have
assessed the health-promoting functions of white fish muscle proteins (WFP) and
red fish muscle proteins (RFP). We therefore evaluated the mechanisms underlying
the alteration of lipid profiles and cholesterol metabolism following the intake
of WFP prepared from cod and RFP prepared from light muscles of tuna. Male Wistar
rats were divided into six dietary groups: casein (23%), WFP (23%), and RFP
(23%), with or without 0.5% cholesterol and 0.1% sodium cholate. Compared to the
WFP-containing diet, the RFP-containing diet supplemented with cholesterol and
sodium cholate significantly increased serum and liver cholesterol contents.
However, in the RFP groups, an alteration in cholesterol metabolism including an
increased tendency to excrete fecal sterols and hepatic cholesterol 7alpha
hydroxylase was related to the reduction of hepatic cholesterol contents. This
phenomenon might be related to the tendency of an increased food intake in RFP
containing diets. These results highlight the differential effects of WFP and RFP
on serum and liver lipid profiles of Wistar rats fed non-cholesterol- or
cholesterol-containing diets under no fasting condition.
PMID- 28702426
TI - The Chemical Characteristics and Immune-Modulating Activity of Polysaccharides
Isolated from Cold-Brew Coffee.
AB - To elucidate new biological ingredients in cold-brew coffee extracted with cold
water, crude polysaccharide (CCP-0) was isolated by ethanol precipitation, and
its immune-stimulating activities were assayed. CCP-0 mainly comprised galactose
(53.6%), mannose (15.7%), arabinose (11.9%), and uronic acid (12.4%), suggesting
that it might exist as a mixture of galactomannan and arabinogalactan. CCP-0
significantly increased cell proliferation on both murine peritoneal macrophages
and splenocytes in a dose dependent manner. CCP-0 also significantly augmented
nitric oxide and reactive oxygen species production by murine peritoneal
macrophages. In addition, macrophages stimulated by CCP-0 enhanced production of
various cytokines such as tumor necrosis factor-alpha, interleukin (IL)-6, and IL
12. In an in vitro assay for intestinal immune-modulating activity, CCP-0 showed
higher bone-marrow cell-proliferation activity through Peyer's patch cells at 100
MUg/mL than the negative control. These results suggest that CCP-0 may
potentially enhance macrophage functions and the intestinal immune system.
PMID- 28702427
TI - Antioxidant and Anticholinesterase Potential of Two Nigerian Bitter Yams Using a
Simulated Gastrointestinal Digestion Model and Conventional Extraction.
AB - The purpose of this study was to evaluate the antioxidant and anticholinesterase
activities of yellow and white bitter yams from South Western Nigeria using
methanolic extraction and simulated gastrointestinal digestion models. The
phenolic compounds in the bitter yam varieties were evaluated by high performance
liquid chromatography with a diode array detector (HPLC-DAD). The total phenolic
content of the bitter yams was measured by the Folin-Ciocalteu method, reductive
potential by assessing the ability of the bitter yam to reduce FeCl3 solution,
and the antioxidant activities were determined by the 2,2-diphenyl-1
picrylhydrazyl radical (DPPH.) scavenging activity, 2,2'-azino-bis(3
ethylbenzothiazoline-6-sulfonic acid) radical cation (ABTS.+) scavenging
activity, nitric oxide radical (NO.) scavenging ability, hydroxyl radical
scavenging ability, and ability to inhibit Fe2+-induced lipid oxidation. The HPLC
DAD analysis revealed the presence of some phenolic compounds in the studied
bitter yam varieties, with varying degree of quantitative changes after cooking.
The antioxidant indices (total phenolic content, total flavonoid content,
reducing power, DPPH. scavenging activity, ABTS.+ scavenging activity, and NO.
scavenging activity) were higher in the simulated gastrointestinal digestion
model compared to the methanolic extract, with the in vitro digested cooked white
bitter yam ranking higher. Similarly, the in vitro digested yams had a higher
inhibitory action against lipid oxidation compared to the methanolic extracts,
with the cooked white bitter yam ranking high. The methanolic extracts and in
vitro enzyme digests showed no acetylcholinesterase inhibitory abilities, while
methanolic extracts and the in vitro enzyme digest displayed some level of
butyrylcholinesterase inhibitory activities. Therefore the studied bitter yams
could be considered as possible health supplements.
PMID- 28702428
TI - Esculetin Inhibits Adipogenesis and Increases Antioxidant Activity during
Adipocyte Differentiation in 3T3-L1 Cells.
AB - This study was conducted to investigate the anti-adipogenic activity of esculetin
(ECT) which is reported to be attributable to the modulation of antioxidant
enzymes during adipogenesis. After six days of ECT treatment of 3T3-L1 cells,
lipid accumulation was determined by Oil red O staining. The levels of
glutathione (GSH) and reactive oxygen species (ROS), and the activities of
antioxidant enzymes including glutathione reductase, glutathione peroxidase
(GPx), and catalase were examined. In addition, the protein expression of
glutamate-cysteine ligase catalytic subunit (GCLC) and heme oxygenase-1 (HO-1)
was measured by Western blot. ECT significantly inhibited lipid accumulation by
approximately 80% and ROS production in a concentration-dependent manner. GSH
level and GPx activity were increased by ECT by approximately 1.3-fold and 1.7
fold compared to the control group, respectively. GCLC and HO-1 expression were
elevated by ECT. These results showed that ECT treatments strongly inhibit
adipogenesis, increase GSH level, and upregulate the expression of GCLC and HO-1,
possibly by decreasing ROS production in 3T3-L1 cells during adipogenesis.
PMID- 28702429
TI - Wild Mushrooms: A Potential Source of Nutritional and Antioxidant Attributes with
Acceptable Toxicity.
AB - This paper describes in detail proximate composition, nutritional profile,
phytochemical constituents, antioxidant activities, antimicrobial potential, and
antihemolytic activity (towards human erythrocytes) of various fractions of wild
Ganoderma lucidum. Proximate analysis established that wild G. lucidum comprises
about 87.02+/-5.45% of moisture, and the remaining part is a rich source of
proteins (8.59+/-0.37%), crude fiber (54.21+/-1.2%), and carbohydrate (35.16%)
with smaller fat content (3.33 %). Similarly, phytochemical screening revealed
the presence of flavonoids (217.51+/-0.30 mg/g), ascorbic acid (116+/-7.32 mg/g),
phenolics (360.72+/-34.07 mg/g), beta-carotenes (0.42+/-0.04 MUg/g), and lycopene
(0.05+/-0.00 MUg/g). Extracts of wild G. lucidum in various solvents provided
first line protection against Escherichia coli and Pasteurella multocida in the
order of ethyl acetate> ethanol> methanol> n-hexane> water. Furthermore, aqueous
and methanolic extracts of wild G. lucidum were found to be safe towards human
erythrocytes. Overall, wild mushroom (G. lucidum) was found to be a good source
of dietary supplements, antimicrobial and antioxidant agents in the pursuance of
its commercial utilization in food and pharmaceutical industries.
PMID- 28702430
TI - Optimization of Subcritical Water Hydrolysis of Rutin into Isoquercetin and
Quercetin.
AB - Maximum production of isoquercetin and quercetin simultaneously from rutin by
subcritical water hydrolysis (SWH) was optimized using the response surface
methodology. Hydrolysis parameters such as temperature, time, and CO2 pressure
were selected as independent variables, and isoquercetin and quercetin yields
were selected as dependent variables. The regression models of the yield of
isoquercetin and quercetin were valid due to the high F-value and low P-value.
Furthermore, the high regression coefficient indicated that the polynomial model
equation provides a good approximation of experimental results. In maximum
production of isoquercetin from rutin, the hydrolysis temperature was the major
factor, and the temperature or time can be lower if the CO2 pressure was
increased high enough, thereby preventing the degradation of isoquercetin into
quercetin. The yield of quercetin was considerably influenced by temperature
instead of time and CO2 pressure. The optimal condition for maximum production of
isoquercetin and quercetin simultaneously was temperature of 171.4 degrees C,
time of 10.0 min, and CO2 pressure of 11.0 MPa, where the predicted maximum
yields of isoquercetin and quercetin were 13.7% and 53.3%, respectively.
Hydrolysis temperature, time, and CO2 pressure for maximum production of
isoquercetin were lower than those of quercetin. Thermal degradation products
such as protocatechuic acid and 2,5-dihydroxyacetophenone were observed due to
pyrolysis at high temperature. It was concluded that rutin can be easily
converted into isoquercetin and quercetin by SWH under CO2 pressure, and this
result can be applied for SWH of rutin-rich foodstuffs.
PMID- 28702431
TI - Isolation of Antifungal Lactic Acid Bacteria (LAB) from "Kunu" against Toxigenic
Aspergillus flavus.
AB - The antifungal activity of isolated lactic acid bacteria (LAB) from a locally
fermented cereal, "Kunu", was tested against toxigenic Aspergillus flavus. The
liquid refreshment, "Kunu", was prepared under hygienic condition using millet,
sorghum, and the combination of the two grains. The antifungal potential of
isolated LAB against toxigenic A. flavus was carried out using both in vitro and
in vivo antifungal assays. The LAB count from prepared "Kunu" ranged from 2.80
*104 CFU/mL to 4.10*104 CFU/mL and Lactobacillus plantarum, Lactobacillus
delbrueckii, Lactobacillus fermentum, Pediococcus acidilactici, and Leuconostoc
mesenteroides were the isolated bacteria. Inhibitory zones exhibited by LAB
against toxigenic A. flavus ranged from 5.0 mm to 20.0 mm. The albino mice
infected with toxigenic A. flavus showed sluggishness, decrease in body weight,
distortion of hair, and presence of blood in their stool, while those treated
with LAB after infection were recovered and active like those in control groups.
Except for the white blood cell that was increased in the infected mice as 6.73
mm3, the packed cell volume, hemoglobin, and red blood cell in infected animals
were significantly reduced (P<0.05) to 29.28%, 10.06%, and 4.28%, respectively,
when compared to the treated mice with LAB and control groups. The antifungal
activity of LAB against toxigenic A. flavus can be attributed to the
antimicrobial metabolites. These metabolites can be extracted and used as
biopreservatives in food products to substitute the use of chemical preservatives
that is not appealing to consumers due to several side effects.
PMID- 28702432
TI - Efficacy of Curcumin in the Modulation of Anxiety Provoked by Sulfite, a Food
Preservative, in Rats.
AB - Sulfites are used as food preservatives and excessive sulfite might disturb the
body systems including the brain. Curcumin shows protective effects on the
nervous system toxicity. The present study aimed to evaluate the protective role
of curcumin in sulfite-induced anxiety in rats. Male rats were divided into five
groups. The rats in groups I to V received distilled water (vehicle of sulfite, 1
mL/d), olive oil (vehicle of curcumin, 1 mL/d), curcumin (100 mg/kg/d), sulfite
(25 mg/kg/d), and sulfite+curcumin, respectively, by daily gastric gavage for 8
weeks. At the end of 8 weeks the rats were tested in the elevated plus-maze for
anxiety. The results showed that concomitant treatment of curcumin during sulfite
consumption prevented the reduction of the time spent in the open arm and
entrance to the open arm (the indexes of anxiety). Besides, an increase was found
in motor activity of the rats in the sulfite+curcumin group compared to the
sulfite-treated animals. Exposure of sulfite in rats can induce anxiety, and
curcumin can act as an anti-anxiety agent.
PMID- 28702433
TI - Korean Solar Salt Ameliorates Colon Carcinogenesis in an AOM/DSS-Induced C57BL/6
Mouse Model.
AB - The effects of Korean solar salt on an azoxymethane (AOM)/dextran sodium sulfate
(DSS)-induced colon cancer C57BL/6 mouse model were studied. Korean solar salt
samples (SS-S, solar salt from S salt field; SS-Yb, solar salt from Yb salt
field), nine-time-baked bamboo salt (BS-9x, made from SS-Yb), purified salt (PS),
and SS-G (solar salt from Guerande, France) were orally administered at a
concentration of 1% during AOM/DSS colon cancer induction, and compared for their
protective effects during colon carcinogenesis in C57BL/6 mice. SS-S and SS-Yb
suppressed colon length shortening and tumor counts in mouse colons. Histological
evaluation by hematoxylin and eosin staining also revealed suppression of
tumorigenesis by SS-S. Conversely, PS and SS-G did not show a similar suppressive
efficacy as Korean solar salt. SS-S and SS-Yb promoted colon mRNA expression of
an apoptosis-related factor and cell-cycle-related gene and suppressed pro
inflammatory factor. SS-Yb baked into BS-9x further promoted these anti
carcinogenic efficacies. Taken together, the results indicate that Korean solar
salt, especially SS-S and SS-Yb, exhibited anti-cancer activity by modulating
apoptosis- and inflammation-related gene expression during colon carcinogenesis
in mice, and bamboo salt baked from SS-Yb showed enhanced anti-cancer
functionality.
PMID- 28702434
TI - Exercise rehabilitation in the fourth industrial revolution.
PMID- 28702435
TI - Interval and continuous aerobic exercise training similarly increase cardiac
function and autonomic modulation in infarcted mice.
AB - The present study aimed to compare the effects of moderate-intensity continuous
and high-intensity interval exercise training (ET) on exercise tolerance, cardiac
morphometry and function, hemodynamic, and cardiac autonomic modulation in
myocardial infarcted mice. Wild-type mice (WT) were divided into four groups:
sedentary WT (S); WT myocardium infarction sedentary (IS); WT myocardium
infarction underwent to moderate-intensity continuous ET (MICT), and WT
myocardium infarction underwent to high-intensity interval ET (MIIT). After 60
days of descending coronary artery ligation, moderate-intensity continuous ET
consisted of running at 60% of maximum, while the high-intensity interval
training consisted of eight sprints of 4 min at 80% of maximum and a 4-min
recovery at 40% of maximum. Both exercises were performed 1 hr a day, 5 days a
week, during 8 weeks. Results demonstrated that IS showed elevated exercise
tolerance, as well as decreased hemodynamic and heart function, and autonomic
control. On the other hand, both programs of ET were equally effective to
increase all parameters, without further differences between the groups. In
conclusion, the results of the present study showed that myocardial infarction
leads to damage in both investigated strains and the two types of physical
exercise attenuated the major impairments provoked by myocardial infarction in
exercise tolerance, cardiac structure, cardiac function, hemodynamic and cardiac
autonomic modulation.
PMID- 28702436
TI - Paternal physical exercise improves spatial learning ability by enhancing
hippocampal neuroplasticity in male pups born from obese maternal rats.
AB - Maternal obesity exerts negative effects on cognitive function and behavior of
the offspring. In the present study, we assessed the effects of paternal physical
exercise on spatial learning ability in relation with hippocampal neuroplasticity
in the rat pups born from the obese maternal rats. There were four experimental
groups: paternal nonexercised male pups from normal maternal rats, paternal
exercised male pups from normal maternal rats, paternal nonexercised male pups
from obese maternal rats, and paternal exercised male pups from obese maternal
rats. Normal diet was supplied for normal maternal rats and high-fat diet was
supplied for obese maternal rats for a 12-week period until mating, and the same
diet for each group continued throughout pregnancy and lactation period. Male
rats in the exercising groups exercised for a 12-week period. Spatial learning
ability was reduced in the male rat pups born from the obese maternal rats.
Expressions of brain-derived neurotrophic factor (BDNF) and tyrosine kinase B
receptor (TrkB) in the hippocampus were suppressed and cell proliferation and
differentiation in the hippocampus were reduced in the male rat pups born from
the obese maternal rats. Paternal treadmill exercise improved spatial learning
ability, increased BDNF and TrkB expressions, and enhanced cell proliferation and
differentiation in the male rat pups born from the obese maternal rats. It can be
suggested that paternal exercise enhances hippocampal neuroplasticity and
consequently improved spatial learning ability in the rat pups born from the
obese maternal rats.
PMID- 28702437
TI - Treadmill exercise with bone marrow stromal cells transplantation potentiates
recovery of locomotor function after spinal cord injury in rats.
AB - Transplantation of bone marrow stromal cells (BMSCs) is regarded as a promising
candidate for the spinal cord injury (SCI). In the present study, we investigated
whether treadmill exercise potentiate the effect of BM-SCs transplantation on the
functional recovery in the SCI rats. The spinal cord contusion injury applied at
the T9-T10 level using the impactor. Cultured BMSCs were transplanted into the
lesion at 1 week after SCI induction. Treadmill exercise was conducted for 6
weeks. Basso-Beattie-Bresnahan (BBB) scale for locomotor function was determined.
Sprouting axons in the lesion cavity were detected by immunofluorescence staining
for neurofilament-200. Brain-derived neurotrophic factor (BDNF) and synapsin-I
expressions were analyzed using western blotting. BMSCs transplantation improved
BBB score and increased expressions of neurofilament-200, BDNF, and synapsin-I in
the SCI rats. Treadmill exercise potentiated the improving effect of BMSCs
transplantation on BBB score in the SCI rats. This potentiating effect of
treadmill exercise could be ascribed to the enhancement of BDNF expression in the
SCI rats.
PMID- 28702438
TI - Examination of levels pentraxin-3, interleukin-6, and C-reactive protein in rat
model acute and chronic exercise.
AB - Different types of exercise occurs damage at the cellular level in the muscles.
Muscle damage caused by exercise is determined creatine kinase, myoglobin, and
increase in levels of acute phase protein and interleukin in blood. The purpose
of this study was investigated the levels of pentraxin-3 (PTX-3), interleukin-6
(IL-6), and C-reactive protein (CRP) following acute and chronic exercising in
rats. Twenty-six Wistar Albino male rats were divided in to three groups. A
treadmill exercise was performed 3 days/week, 10 min/day for 1 week in acute
groups. In chronic group, exercise performed 7 days/week, 60 min/day for 4 weeks.
At the end of the experiment, plasma PTX-3, IL-6, and CRP levels were measured.
In current study, the PTX-3, IL-6, and CRP levels not observed statistically
significant difference among control, acute, and chronic groups. The levels IL-6
and CRP were not significantly different between acute and chronic exercise
groups (P>0.05). However, the level of PTX-3 was found to be higher in the
chronic group compared to the acute group (P<0.05). The PTX-3 level increase on
chronic exercise-induced muscle damage. Accorting to our results, we think that
PTX-3 may have a protect role on muscle damage during chronic exercises.
PMID- 28702439
TI - Physiological adaptations induced by swimming in mice fed a high fat diet.
AB - This study examined physiological variables of animals fed with a high-fat diet
(HFD) or with a normal diet (ND) subjected to swimming at low and moderate level.
Over 16 weeks, a group of animals was fed with HFD or ND, and at the 8 weeks,
they started swimming with 50% or 80% of the maximum load achieved in the
progressive work test. Weekly, body weight and the amount of ingested food were
registered. The glycemic level was measured at the beginning, middle and at the
end of the experiment. Adipose tissue, gastrocnemius muscles and hearts were
collected for morphometry. The results showed that the animals fed an HFD had a
minor caloric intake; however, the HFD increased body weight and adiposity,
likely causing cardiac hypertrophy and an increase in the glycemic level. In this
context, swimming with an 80% load contributed positively to weight control,
adiposity, glycemic level, to control cardiac hypertrophy and induce hypertrophy
in the gastrocnemius muscle. All parameters assessed showed better results for
the ND animals. Therefore, the importance of fat consumption was emphasized in
relation to obesity onset. The practice of swimming with an 80% load produced
greater benefits than swimming with a 50% load for overweight treatment.
PMID- 28702440
TI - Association between exercise-induced asthma and parental socio-economic status
among school-aged adolescents in a semiurban community in Nigeria.
AB - This study investigated the prevalence and association between exercise-induced
asthma (EIA) and parental socio-economic status (PSES) among school-aged
adolescents in a semiurban community in Nigeria. Three hundred and eighty-five
adolescents (185 male and 200 female adolescents) whose ages ranged between 10
and 19 years participated in this cross-sectional study. Participants were
recruited from four government approved secondary schools in Ido-Ekiti using a
multistage sampling technique. Peak expiratory flow rate (PEFR) was assessed at
baseline and after 6-min run test (6-MRT) on a level playing ground using a
standard peak flow meter. PEFR measurements were repeated at 5th, 10th, 15th, and
20th min post 6-MRT. Participants who had >15.0% PEFR fall were considered to
have EIA. PSES was assessed using a validated socio-economic status
questionnaire. Descriptive and inferential statistics were used to analyze data.
Alpha level was set at P<0.05. The mean ages of males and females were 13.9+/-2.0
and 13.8+/-1.6 years, respectively. More than half of the participants, 58.2% had
EIA (>15.0% PEFR scores) while 53.5% belonged to middle PSES class. There was no
significant difference between PEFR scores of male and female participants at
baseline and 5th min post 6-MRT. However, male participants had significant
higher PEFR than the female counterparts at 10th (t=2.090, P=0.037), 15th
(t=2.162, P=0.031), and 20th min (t=2.978, P=0.003). There was significant
association between EIA and PSES (chi2=152.4; P=0.001). The prevalence of EIA is
very high among school-aged adolescents in Nigeria and was significantly
associated with PSES.
PMID- 28702441
TI - Nationwide survey of cancer center programs in Korea.
AB - This study was conducted to investigate cancer centers established for the
purpose of satisfying various needs about cancer, improving the cancer treatment
environment, and subdividing services ranging from diagnosis, treatment, and
rehabilitation to palliative care. To this end, the authors have surveyed
programs in 17 cancer centers representing Korea, including 12 national cancer
centers and five major hospitals. As a result, it was found that the most common
type of lecture program was disease management, followed by health care and
hospitalization, while the most common type of participation program was
psychological relief, followed by physical activity. The most frequently operated
type of program was found to be psychological relief, followed by physical
activity and health care in the regional cancer centers, while the most
frequently operated type was disease management, followed by psychological relief
and health care in the five major hospitals. The proportion of physical activity
was very high in two regional cancer centers, whereas five regional cancer
centers did not offer physical activity programs at all. In the five major
hospitals, physical activity programs were conducted regularly at least once a
month or at least once a week. In addition, further studies are required to
provide professional and detailed medical services for the establishment and
operation of programs for cancer patient management and the environmental aspects
of the hospital.
PMID- 28702442
TI - Kinematics and neuromuscular recruitment during vertical treadmill exercise.
AB - The vertical treadmill (VertiRun) is an unresearched, partial weight-bearing
exercise mode for lower limb rehabilitation. The user undertakes a "running-like"
action whilst body weight is supported by a bench and the limb is drawn downwards
against overhanging resistance cables on a vertically hung nonmotorised
treadmill. This study sought to describe the kinematics and neuromuscular
recruitment during VertiRun exercise in the supine, 40 degrees , and 70 degrees
postures. Twenty-one healthy male participants (age, 25+/-7 years; stature,
1.79+/-0.07 m; body mass, 77.7+/-8.8 kg) volunteered for sagittal plane kinematic
analysis of the ankle, knee and hip and electromyography of lower limb
musculature in all three postures. Results indicated similar kinematic and
neuromuscular profiles in the 40 degrees and 70 degrees postures which differed
from the supine. Regardless of posture, a basic movement pattern was observed
where the hamstrings and gastrocnemius muscles were active to extend the hip,
flex the knee, plantarflex the ankle and draw the leg down the treadmill belt in
the contact phase. The rectus femoris and tibialis anterior were active to flex
the hip and knee, and dorsiflex the ankle to draw the leg upwards during the
swing phase. The vasti muscles were not active during VertiRun exercise. The
VertiRun demonstrated similar kinematic and neuro-muscular patterns to overground
gait, allows workload progression based on effort and posture changes, and is a
low-impact exercise mode that could maintain physical fitness without loading
injured tissues. This study suggests that the VertiRun could supplement
rehabilitation programmes for lower-limb injuries.
PMID- 28702443
TI - Physical exercise programs at Basic Healthcare Units decrease body fat and
improve the functional capacity of women over 50 years old.
AB - This study verified the effects of a physical exercise program performed at Basic
Healthcare Units on the body composition and functional capacity of women over 50
years old and to compare these variables according to age. Forty-eight women
(age, 65.4+/-7.3 years) were assessed. The program lasted 20 weeks, and was
conducted 2 times per week, 60 min/day. Body mass and height were collected and
body mass index (BMI) was calculated. Bioelectrical impedance was used to
estimate fat mass and fat free mass. Functional capacities: handgrip test, Timed
Up and Go (TUG) test, and Guralnick test were assessment. Weight (68.7+/-12.5
[pre]*66.8+/-12.5 [post], P<0.001), BMI (28.5+/-4.1 kg/m2 [pre]*27.6+/-4.0 kg/m2
[post], P<0.001), and fat mass (28.4+/-7.8 kg [pre]*26.4+/-7.3 kg [post],
P<0.001) were decreased. For functional capacity, handgrip (21.2+/-5.8 kg
[pre]*22.9+/-6.9 kg [post], P=0.014), lower limb strength (12.0+/-3.0 sec
[pre]*8.5+/-2.2 sec [post], P<0.001), TUG (8.4+/-1.5 sec [pre]*7.6+/-1.1 se
[post], P<0.001) and Guralnik tests (10.6+/-1.6 [pre]*11.8+/-0.5 [post], P<0.001)
were improved. 20 weeks of exercise program performed at Basic Healthcare Units
decreased body fat and improvement of functional capacity of women over 50 years
old and there was difference according to age only on the body composition
variables.
PMID- 28702444
TI - Combined training (strength plus aerobic) potentiates a reduction in body fat but
only functional training reduced low-density lipoprotein cholesterol in
postmenopausal women with a similar training load.
AB - The aim of this study was to compare the effects of combined (CT; strength plus
aerobic) and functional training (FT) on the body composition and metabolic
profile with a similar training load in postmenopausal women. The participants
were divided into three groups: CT (n=20), FT (n=17), and control group (CG,
n=15). The trunk FM, fat mass (FM), percentage of FM (FM%), and fat-free mass
were estimated by dual-energy X-ray absorptiometry. The metabolic profile,
glucose, triacylglycerol, total cholesterol, high-density lipoprotein cholesterol
and low-density lipoprotein cholesterol (LDL-c) were assessed. There were main
effects of time in trunk fat, FM, and FM% (P<0.05). There were statistically
significant interaction for FM (P=0.015), FM% (P=0.017) with lower values for CT
group. For LDL-c, there was significant interaction (P=0.002) with greater values
for FT group in relation to CG and CT. Furthermore, when performed the post hoc
test on the "mean absolute differences" (Delta), it can observed statistically
significant difference between FT, CT, and CG (-13.0+/-16.5 mg/dL vs. 4.8+/-18.4
mg/dL vs. 9.2+/-18.8 mg/dL, P<0.05). In conclusion, when training loads are
equivalent CT potentiated a reduction in FM and FM%, however, only FT reduced LDL
c in postmenopausal women.
PMID- 28702445
TI - Effect of a professional soccer match in skin temperature of the lower limbs: a
case study.
AB - The purpose of this study is to analyze the relationship between lower limbs skin
temperature (Tsk) recorded by infrared thermography and creatine kinase (CK)
response following an official soccer game. A professional soccer player, from
the first division Brazilian League, defender, 27 years and 183 cm of height was
analyzed. Measures of Tsk with a thermal camera and blood CK concentrations were
obtained 24 hr before (24H-PRE), 24 (24H-POST) and 48 hr (48H-POST) after an
official match. The results showed that CK values were 193 U/L 24 hr before,
rising to 1,083 U/L 24 hr after the game and 414 U/L 48 hr after the game.
Anterior thigh Tsk was 31.5 degrees C, 33.8 degrees C, and 31.8 degrees C in the
moments 24H-PRE, 24H-POST, and 48H-POST, respectively. Similarly, anterior leg
presented temperature of 31.2 degrees C, 33.3 degrees C, and 31.5 degrees C at
the same moments. Qualitative analysis of the thermograms showed that whole lower
limbs are much warmer 24 hr after the match and certain areas as the right
anterior thigh, the left anterior leg, both anterior ankles, and both posterior
thighs have not fully recovered their initial Tsk 48 hr after the match. The
results of this study indicate that participation in a professional soccer match
can lead to significant increases in Tsk values measured by IRT 24 hr after the
match. Considering this variable as an indicator of muscular damage, it could
help in the process of training control, being part of an injury prevention
program in professional soccer clubs.
PMID- 28702446
TI - Comparison of abdominal muscle activity during abdominal drawing-in maneuver
combined with irradiation variations.
AB - Many experts have used an indirect method for enhancing strength and performance
of muscles in clinical practice. The indirect method, which called an irradiation
is a basic procedure of proprioceptive neuromuscular facilitation, there is
little research related the effects of irradiation. This study investigated
abdominal muscle activity during abdominal drawing-in maneuver (ADIM) combined
with irradiation variations. The study recruited 42 healthy, young adults who
were divided randomly into three groups according to which intervention they
received. The first group performed the ADIM combined with coactivation of the
pelvic floor muscle. The second group performed the ADIM combined with the
irradiation resulting from dorsiflexion of the ankle. The third group performed
the ADIM combined with the irradiation resulting from bilateral arm extension.
Electromyography data were collected from the rectus abdominis, external oblique
abdominis, and transversus abdominis/internal oblique abdominis (TrA/IO) muscles
during ADIM combined with irradiation variations. There were significant
differences in the abdominal muscle activity and the preferential contraction
ratio of the TrA/IO among the three groups (P<0.05). ADIM combined with
irradiation resulting from bilateral arm extension may be effective for enhancing
the deep and superficial abdominal muscles of healthy people and athletes. The
ADIM without the irradiation is advantageous for recovering motor control of the
TrA/IO.
PMID- 28702447
TI - Effects of physical activity on debilitating behaviours in 13- to 20-year-old
males with severe autism spectrum disorder.
AB - The presented study investigated the extent to which engaging in a therapeutic
sporting programme in males with severe autism spectrum disorder (ASD) improves
the debilitating behaviours commonly associated with ASD. Furthermore, the views
of parents of the autistic participants were assessed concerning the
effectiveness of the programme. Participants were eight 13- to 20-year-old males
born in the United Kingdom from a school and sports college for pupils with
severe learning difficulties. The selection was using volunteer sampling from the
"Monday Club" initiative, run by Saracens Sports Foundation in partnership with a
local school and specialist sports college. The Gilliam Autism Rating Scale, 3rd
edition was administered to identify and measure the severity of ASD behaviours
at four time periods namely: at programme entry as the baseline (Time 1, T1), a
second time after 8 weeks (Time 2, T2), a third time after 16 weeks (Time 3, T3),
and a fourth time post programme (Time 4, T4). The results showed that for the
more severe cases of ASD (Autism Index >101) there was no positive change in
subscale performance from T1 to T2. For milder cases (Autism Index, 71-100) there
were subtle non-significant improvements on the subscale scores from T1 to T2. Of
the 6 subscales at T2, emotional responses, cognitive style, and maladaptive
speech approached significance at the P=0.05 level. At T3 and T4, there was also
no statistically significant improvement in ASD behaviours compared to the
baseline for either condition. Finally parents' were "very satisfied" with their
child's participation in the physical activity programme.
PMID- 28702448
TI - Study of gait using weighted vests on balance with paraplegic patients.
AB - The aims of this study were to identify static and dynamic balance with the
addition of weighted vests for the rehabilitation of paraplegic patients. The
study was conducted using weighted vest exercises with applied optimal weight
ratios. Ten paraplegic patients who use custom orthosis were enrolled for
experiments including static standing and dynamic gait with a weighted vest. We
set weight ratios as 0%, 10%, and 15% of the patients' weight. A plantar pressure
device was used for static balance tests for excursion and velocity of center of
pressure and we identified dynamic balance through the tool of Timed Up and Go
(TUG) test. The results of static and dynamic balance in 0%, 10%, and 15% weight
ratios did not have statistically significant differences, but we found an
increasing tendency of sway excursion from nonweight (0%) to weight ratios (10%,
15%) in static balance when weight is applied. Sway excursion in anteroposterior
direction is greater than mediolateral sway. In dynamic balance, the TUG results
showed a more delayed time when weight ratios were applied. In conclusion, we
have to focus on balance training with anteroposterior direction to upgrade a
patient's balance and prevent falls. Exercises with weighed vests are more useful
than nonweighted but there is no difference between 10% and 15% weight ratios.
Weighted vest exercises may play a role in the rehabilitation of balance in those
with paraplegia.
PMID- 28702449
TI - Six-week physical rehabilitation protocol for anterior shoulder dislocation in
athletes.
AB - Anterior shoulder dislocations are common in young athletes. The mechanism for
the first or primary shoulder dislocation may involve a collision or a fall
typically with the arm in an abducted and externally rotated position. The aim of
this study was to design a physical rehabilitation program using the elastic band
and resistive exercise to improve joint strength and range of motion in
individuals diagnosed with a first-time shoulder dislocation. Twelve physically
active males with a first-time acute shoulder dislocation were asked to
volunteer. Participants began a physical rehabilitation program 2 weeks after the
shoulder dislocation, which was confirmed by a referring physician. The
rehabilitation program was 6 weeks in duration and required the participants to
engage in progressive resistive loads/duration using elastic bands and weights 5
days per week. Pretest and posttest measures included shoulder strength and range
of motion. All outcome measures were compared between the injured and uninjured
shoulder, which served as the control condition in this study. There were
statistically significant differences between the injured and uninjured shoulder
for measures of strength and range of motion during pretests (P<0.01) but not
post-tests (P<0.53). Finally, there were no differences between shoulders in
regards to the volume measure suggesting that any changes in muscle atrophy or
swelling were not detected. The physical rehabilitation program proposed in this
study was effective at improving strength and range of motion in the injured
shoulder as evidenced by the similarity in posttest values between the injured
and uninjured shoulder.
PMID- 28702450
TI - Effects of taping therapy for carpal space expansion on electrophysiological
change in patients with carpal tunnel syndrome.
AB - Taping therapy is one of the most conservative treatments for carpal tunnel
syndrome (CTS). Preceding research studied on pain control, grip strength, and
wrist function but no studies have been reported on electrophysiolgical changes
after taping therapy. The aim of this study is to evaluate the effects of taping
therapy for carpal space expansion on electrophysiological in 20 female patients
aged from 40s to 60s with CTS. Experimental group applied taping therapy for
carpal space expansion twice a week for 4 weeks and control group did not. There
were significant differences between distal motor latency (DML) and sensory nerve
conduction velocity (SNCV), but no difference between compound muscle action
potential and sensory nerve action potential (SNAP) after 4 weeks taping
treatment. Also, there was a significant difference in DML, SNCV, and SNAP in
between groups. In conclusion, taping therapy for carpal space expansion can help
to reduce the pressure of the carpal tunnel in CTS patients with mild symptoms.
PMID- 28702451
TI - Comparative effectiveness of two stabilization exercise positions on pain and
functional disability of patients with low back pain.
AB - The study investigated the effects of two stabilization exercise positions (prone
and supine) on pain intensity (PI) and functional disability (FD) of patients
with nonspecific chronic low back pain (NSCLBP). The 56 subjects that completed
the study were randomly assigned into stabilization in prone (SIP) (n=19),
stabilization in supine (SIS) (n=20), and prone and supine (SIPS) position (n=17)
groups. Subjects in all the groups received infrared radiation for 15 min and
kneading massage at the low back region. Subjects in SIP, SIS, and SIPS groups
received stabilization exercise in prone lying, supine lying and combination of
both positions respectively. Treatment was applied twice weekly for eight weeks.
PI and FD level of each subject were measured at baseline, 4th and 8th week of
the treatment sessions. Data were analyzed using descriptive and inferential
statistics. The alpha level was set at P<0.05. Within-group comparison indicated
that PI and FD at the 4th and 8th week were significantly reduced (P<0.001) when
compared with baseline in all the three groups. However, the result showed that
there was no significant difference in the PI and FD at the 8th week (P>0.05) of
the treatment sessions across the three groups when compared. It can be concluded
that stabilization exercises carried out in prone, supine and combination of the
two positions were equally effective in managing pain and disability of patients
with NSCLBP. However, no position was superior to the other.
PMID- 28702452
TI - Bronchial or Laryngeal Obstruction Induced by Exercise?
AB - A child suspected of exercise-induced laryngeal obstruction and asthma is
examined by laryngoscopy and respiratory resistance (Rrs) after exercise
challenge. Immediately at exercise cessation, the visualized adduction of the
larynx in inspiration is reflected in a paroxystic increase in Rrs. While normal
breathing has apparently resumed later on during recovery from exercise, the
pattern of Rrs in inspiration is observed to reoccur following a deep breath or
swallowing. The procedure may thus help diagnosing the site of exercise-induced
obstruction when laryngoscopy is not available and identify re-inducers of
laryngeal dysfunction.
PMID- 28702453
TI - Psychometric Properties of the Urdu Version of Diabetes Knowledge Questionnaire.
AB - OBJECTIVE: Patient education is a key element in the treatment of diabetes.
Assessment of diabetes knowledge is important for optimum treatment. For the
assessment of diabetes knowledge, validated tool is essential. None of such
validated tool is available in Urdu language. Therefore, the aim of this study
was to translate and examine the psychometric properties of the 24-item Urdu
version of Diabetes Knowledge Questionnaire (DKQ) among type 2 diabetes patients.
METHODS: Standard "forward-backward" process was used to translate DKQ into Urdu
language. Later, it was validated on a convenience sample of 130 patients with
type 2 diabetes, between July and September 2016. Internal consistency was
assessed by reliability analysis, one-way analysis of variance was applied for
known group validity and multivariate linear logistic regression was applied for
identifying significant predictors for patients' DKQ score. RESULTS: Good
internal consistency was observed for DKQ (Cronbach's alpha = 0.702). The mean
HbA1c of the patients was 8.55% (+/-1.91). DKQ scores of patients' with "good
glycemic control" (14.22 +/- 2.4) were observed significantly higher (P < 0.05)
than patients with "poor glycemic control" (12.56 +/- 2.75). Multiple linear
regression revealed that patients' HbA1c (OR -0.17, CI -1.111, -0.023) and
patients' education (OR 0.17, CI -0.032, 0.758) were significant predictors for
DKQ sum score. CONCLUSION: Urdu version of the DKQ is a valid and reliable
instrument for adequate estimation of disease knowledge and its association with
glycemic control in type 2 diabetes patients in Pakistan.
PMID- 28702454
TI - Corrigendum: Relationship between Human Immunodeficiency Virus (HIV) Knowledge,
HIV-Related Stigma, and HIV Testing among Young Black Adults in a Southeastern
City.
AB - [This corrects the article on p. 47 in vol. 5, PMID: 28349049.].
PMID- 28702455
TI - Synergistic Interactions of a Synthetic Lubricin-Mimetic with Fibronectin for
Enhanced Wear Protection.
AB - Lubricin (LUB), a major mucinous glycoprotein of mammalian synovial fluids, is
believed to provide excellent lubrication to cartilage surfaces. Consequently,
when joint disease or replacement leads to increased friction and surface damage
in the joint, robust synthetic LUB alternatives that could be used
therapeutically to improve lubrication and surface protection are needed. Here,
we report the characterization of a lubricating multiblock bottlebrush polymer
whose architecture was inspired by LUB, and we investigate the role of
fibronectin (FN), a glycoprotein found in the superficial zone of cartilage, in
mediating the tribological properties of the polymer upon shear between mica
surfaces. Our surface forces apparatus (SFA) normal force measurements indicate
that the lubricin-mimetic (mimLUB) could be kept anchored between mica surfaces,
even under high contact pressures, when an intermediate layer of FN was present.
Additional SFA friction measurements show that FN would also extend the wearless
friction regime of the polymer up to pressures of 3.4 MPa while ensuring stable
friction coefficients (MU ~ 0.28). These results demonstrate synergistic
interactions between mimLUB and FN in assisting the lubrication and wear
protection of ideal (mica) substrates upon shear. Collectively, these findings
suggest that our proposed mimLUB might be a promising alternative to LUB, as
similar mechanisms could potentially facilitate the interaction between the
polymer and cartilage surfaces in articular joints and prosthetic implants in
vivo.
PMID- 28702456
TI - Growing Pains at Hospitals: Opportunities and Issues of Service Expansion in
Maximum Care.
AB - PURPOSE: Due to the demographic change morbidity raises the demand for medical
hospital services as well as a need for medical specialization, while economic
and human resources are diminishing. Unlike other industries hospitals do not
have sufficient data and adequate models to relate growing demands and increasing
performance to growth in staff capacity and to increase in staff competences.
METHOD: Based on huge medical data sample covering the years from 2010 to 2014
with more than 150,000 operations of the Department for Anesthesiology at the
University Hospital Muenster, Germany, comparisons are drawn between the
development of medical services and the development of personnel capacity and
expertise. RESULTS: The numbers of surgical operations increased by 21% and "skin
incision to closure" time by 17%. Simultaneously, personnel capacity grew by 16%
largely resting upon recruiting first-time employees. Expertise measured as
"years of professional experience" dwindled from 10 years to 5.4 years on average
and staff turnover accelerated. CONCLUSION: Static benchmark data collected at
fixed reference dates do not sufficiently reflect the nexus between capacity and
competence and do not reflect the dynamic changes in a hospital's requirements
for expertise and specialization, at all. Staff turnover leads to a loss of
experience, which jeopardizes patient safety and hampers medical specialization.
In consequence of the dramatic shortage of medical specialists, drop-off rates
must be reduced and retention rates must be increased. To that end, working
conditions need to be fundamentally converted for a multigeneration,
multicultural, and increasingly female workforce.
PMID- 28702457
TI - Multiple Myeloma Cells Express Key Immunoregulatory Cytokines and Modulate the
Monocyte Migratory Response.
AB - Multiple myeloma (MM) is a plasma cell disorder that still remains incurable. The
immune dysfunction of the host is a striking characteristic of MM, leading to
tumor growth and reducing the survival rate of patients. Monocytes are precursors
of conventional dendritic cells (DCs), a major player in the immunity mechanisms
driving protective T cell responses against tumor. Herein, we report that human
MM RPMI 8226 cell line shows a pronounced chemoattractant activity for monocytes
and also expresses enhanced levels of the leukocyte chemotactic cytokines CXCL12,
CCL5, MIP-1beta, and CXCL10 in association with elevated levels of both key
immunoregulatory interleukins such as IL-4 and IL-10. This cytokine profile was
observed together with reduced expression of IFN-gamma by MM RPMI 8226 cell line,
a determinant interleukin involved in the acquisition of cellular-mediated
protective responses against tumor cells. We further demonstrate that MM RPMI
8226 cell line expresses elevated levels of soluble form of the intercellular
adhesion molecule-1 known to inhibit antitumoral T cell responses. This
attractive modulation of immune responses by MM cells might provide a means to
impair early antitumor responses during the establishment of cytokine-mediated
immunosuppressive tumor niche.
PMID- 28702459
TI - A Review of Quantitative Tools Used to Assess the Epidemiology of Porcine
Reproductive and Respiratory Syndrome in U.S. Swine Farms Using Dr. Morrison's
Swine Health Monitoring Program Data.
AB - Porcine reproductive and respiratory syndrome (PRRS) causes far-reaching
financial losses to infected countries and regions, including the U.S. The Dr.
Morrison's Swine Health Monitoring Program (MSHMP) is a voluntary initiative in
which producers and veterinarians share sow farm PRRS status weekly to contribute
to the understanding, in quantitative terms, of PRRS epidemiological dynamics
and, ultimately, to support its control in the U.S. Here, we offer a review of a
variety of analytic tools that were applied to MSHMP data to assess disease
dynamics in quantitative terms to support the decision-making process for
veterinarians and producers. Use of those methods has helped the U.S. swine
industry to quantify the cyclical patterns of PRRS, to describe the impact that
emerging pathogens has had on that pattern, to identify the nature and extent at
which environmental factors (e.g., precipitation or land cover) influence PRRS
risk, to identify PRRS virus emerging strains, and to assess the influence that
voluntary reporting has on disease control. Results from the numerous studies
reviewed here provide important insights into PRRS epidemiology that help to
create the foundations for a near real-time prediction of disease risk, and,
ultimately, will contribute to support the prevention and control of, arguably,
one of the most devastating diseases affecting the North American swine industry.
The review also demonstrates how different approaches to analyze and visualize
the data may help to add value to the routine collection of surveillance data and
support infectious animal disease control.
PMID- 28702458
TI - Cocoa Diet and Antibody Immune Response in Preclinical Studies.
AB - The ability of cocoa to interact with the immune system in vitro and in vivo has
been described. In the latter context, a cocoa-enriched diet in healthy rats was
able to modify the immune system's functionality. This fact could be observed in
the composition and functionality of lymphoid tissues, such as the thymus,
spleen, and lymph nodes. Consequently, immune effector mechanisms, such as
antibody synthesis, were modified. A cocoa-enriched diet in young rats was able
to attenuate the serum levels of immunoglobulin (Ig) G, IgM, and IgA and also the
intestinal IgM and IgA secretion. Moreover, in immunized rats, the intake of
cocoa decreased specific IgG1, IgG2a, IgG2c, and IgM concentrations in serum.
This immune-regulator potential was then tested in disease models in which
antibodies play a pathogenic role. A cocoa-enriched diet was able to partially
prevent the synthesis of autoantibodies in a model of autoimmune arthritis in
rats and was also able to protect against IgE and T helper 2-related antibody
synthesis in two rat models of allergy. Likewise, a cocoa-enriched diet prevented
an oral sensitization process in young rats. In this review, we will focus on the
influence of cocoa on the acquired branch of the immune function. Therefore, we
will focus on how a cocoa diet influences lymphocyte function both in the
systemic and intestinal immune system. Likewise, its potential role in preventing
some antibody-induced immune diseases is also included. Although further studies
must characterize the particular cocoa components responsible for such effects
and nutritional studies in humans need to be carried out, cocoa has potential as
a nutraceutical agent in some hypersensitivity status.
PMID- 28702460
TI - Seroprevalence and Distribution of Contagious Bovine Pleuropneumonia in Ethiopia:
Update and Critical Analysis of 20 Years (1996-2016) Reports.
AB - Contagious bovine pleuropneumonia (CBPP), infectious and highly contagious
diseases of cattle in Africa, is the only bacterial disease in the OIE list A
diseases. This severe respiratory disease of cattle is the second most important
transboundary animal disease in Africa after rinderpest. CBPP is caused by
Mycoplasma mycoides subsp. mycoides SC (small colony bovine biotype) and it is
endemic disease in many African countries including Ethiopia. This paper
systematically reviews prevalence report at herd and individual animal level for
the last 20 years (1996-2016) with main aim of making comprehensive document
regarding the seroprevalence and distribution of CBPP in Ethiopia. The paper is
therefore helpful in knowing the past and current disease status and also to
forecast the future and possible prevention option in the country. So far, the
seroprevalence that ranges from 0.4 to 96% was reported from different export
quarantine centers and production areas in Ethiopia. The reported seroprevalence
is significantly associated with different agro-ecology of the country and the
highest was reported from lowland in which 40% of livestock population was kept.
The recent seroprevalence studies report from different areas of the country also
indicated as CBPP is posing a major threat to cattle production in many parts of
the country, thereby causing considerable economic losses through morbidity and
mortality. This disease also causes restriction on the trade of animals and
animal products internationally and accounts for a loss of over 8.96 million US
dollars per year in Ethiopian situation. Thus, a great attention should be given
both at production areas and the quarantine stations as its occurrence may affect
the export earnings of the country, thereby threatening the livelihood of
pastoralists and national economy of the country.
PMID- 28702461
TI - Antioxidant System Response and cDNA-SCoT Marker Profiling in Phoenix dactylifera
L. Plant under Salinity Stress.
AB - Many Phoenix dactylifera (date palm) cultivars are grown in the arid and semiarid
regions of the world, including Saudi Arabia. P. dactylifera is highly tolerant
to salinity stress. To investigate the response of Khalas cultivar of P.
dactylifera, two-month-old plants were treated with sodium chloride (50, 100, and
150 mM NaCl) for three months. Our result showed that proline content was higher
in all treated plants compared to control plants. Thiobarbituric acid reactive
substances (TBARS) were increased at 100 and 150 mM NaCl treatments; however, the
result was found nonsignificant between control and plants treated at 50 mM NaCl.
Similarly, enzyme activities of catalase (CAT) and superoxide dismutase (SOD)
were 0.805 and 0.722 U/mg protein/min, respectively, and were greater at 100 and
150 mM NaCl treatments compared to the control plants. Total chlorophyll content
and fresh weight of shoots and roots decreased substantially with the increase of
salinity. A cDNA start codon-targeted (cDNA-SCoT) marker showed a variation in
different gene expressions profiling between treated and untreated plants under
various NaCl concentrations.
PMID- 28702462
TI - Adoptive Cell Therapy of Induced Regulatory T Cells Expanded by Tolerogenic
Dendritic Cells on Murine Autoimmune Arthritis.
AB - OBJECTIVE: Tolerogenic dendritic cells (tDCs) can expand TGF-beta-induced
regulatory T cells (iTregs); however, the therapeutic utility of these expanded
iTregs in autoimmune diseases remains unknown. We sought to determine the
properties of iTregs expanded by mature tolerogenic dendritic cells (iTregmtDC)
in vitro and explore their potential to ameliorate collagen-induced arthritis
(CIA) in a mouse model. METHODS: After induction by TGF-beta and expansion by
mature tDCs (mtDCs), the phenotype and proliferation of iTregmtDC were assessed
by flow cytometry. The ability of iTregs and iTregmtDC to inhibit CD4+ T cell
proliferation and suppress Th17 cell differentiation was compared. Following
adoptive transfer of iTregs and iTregmtDC to mice with CIA, the clinical and
histopathologic scores, serum levels of IFN-gamma, TNF-alpha, IL-17, IL-6, IL-10,
TGF-beta and anti-CII antibodies, and the distribution of the CD4+ Th subset were
assessed. RESULTS: Compared with iTregs, iTregmtDC expressed higher levels of
Foxp3 and suppressed CD4+ T cell proliferation and Th17 cell differentiation to a
greater extent. In vivo, iTregmtDC reduced the severity and progression of CIA
more significantly than iTregs, which was associated with a modulated
inflammatory cytokine profile, reduced anti-CII IgG levels, and polarized
Treg/Th17 balance. CONCLUSION: This study highlights the potential therapeutic
utility of iTregmtDC in autoimmune arthritis and should facilitate the future
design of iTreg immunotherapeutic strategies.
PMID- 28702463
TI - Supporting Quality Data Systems: Lessons Learned from Early Implementation of
Routine Viral Load Monitoring at a Large Clinic in Lilongwe, Malawi.
AB - Successful viral load programs rely on the presence of data systems and high
quality of patient data. Using a cohort of 49 patients at Partners in Hope, a
large, urban HIV clinic in Malawi, we performed a quality improvement assessment
of a new viral load program with a focus on accuracy of data collected from
patients as well as adherence to Malawi HIV Guidelines in regard to response to
elevated viral loads (>=1,000 copies/mL). Data were obtained from three parallel
medical record systems to investigate the proportion of patients with a repeat
viral load and whether the three data systems agreed in regard to
sociodemographic and clinical data. Fewer than 30% of patients had a repeat viral
load within six months, as recommended in the Malawi HIV Guidelines. There were
significant problems with data agreement across the three parallel databases used
for care. Date of birth was consistent for 55.1% (N=27) of patients, while a
different date of birth was noted in all three sources for 10.2% of pateints
(N=1). For 65.3% (N=32), the viral load from the laboratory did not match the
recorded viral load in the electronic or paper record. Scale-up of viral load
monitoring must be accompanied by the development of data systems that support
workflow from sample collection to lab and back to provider. Education of
providers and strategies for data collection with minimal errors can facilitate
scale-up of high quality programs.
PMID- 28702464
TI - A cost-effective RNA extraction technique from animal cells and tissue using
silica columns.
AB - Ribonucleic acid (RNA) is widely used in molecular biology assays, and some of
the most common assays include: northern blotting and RT-PCR gene expression
analysis. RNA is generally extracted by two methods: phenol-chloroform or
commercially available silica spin column kits. Phenol-chloroform extraction is
generally more economical; however, it produces hazardous byproducts, and
leftover chemicals in the sample that can inhibit downstream applications.
Commercial kits usually have simple set ups and short preparation time; however,
they can introduce a significant expense to laboratory budgets. Here we have
created a method to extract RNA using generic silica columns and readily
available reagents while maintaining a high yield and purity.
PMID- 28702465
TI - A Dynamic Transmission Model to Evaluate the Effectiveness of Infection Control
Strategies.
AB - BACKGROUND: The advancement of knowledge about control of antibiotic resistance
depends on the rigorous evaluation of alternative intervention strategies. The
STAR*ICU trial examined the effects of active surveillance and expanded barrier
precautions on acquisition of methicillin-resistant Staphylococcus aureus (MRSA)
and vancomycin-resistant Enterococcus (VRE) in intensive care units. We report a
reanalyses of the STAR*ICU trial using a Bayesian transmission modeling
framework. METHODS: The data included admission and discharge times and
surveillance test times and results. Markov chain Monte Carlo stochastic
integration was used to estimate the transmission rate, importation, false
negativity, and clearance separately for MRSA and VRE. The primary outcome was
the intervention effect, which when less than (or greater than) zero, indicated a
decreased (or increased) transmission rate attributable to the intervention.
RESULTS: The transmission rate increased in both arms from pre- to
postintervention (by 20% and 26% for MRSA and VRE). The estimated intervention
effect was 0.00 (95% confidence interval [CI], -0.57 to 0.56) for MRSA and 0.05
(95% CI, -0.39 to 0.48) for VRE. Compared with MRSA, VRE had a higher
transmission rate (preintervention, 0.0069 vs 0.0039; postintervention, 0.0087 vs
0.0046), higher importation probability (0.22 vs 0.17), and a lower clearance
rate per colonized patient-day (0.016 vs 0.035). CONCLUSIONS: Transmission rates
in the 2 treatment arms were statistically indistinguishable from the pre- to
postintervention phase, consistent with the original analysis of the STAR*ICU
trial. Our statistical framework was able to disentangle transmission from
importation and account for imperfect testing. Epidemiological differences
between VRE and MRSA were revealed.
PMID- 28702466
TI - A 79-Year-Old Man With Chronic Aspiration and an 18F-Fluorodeoxyglucose-Positron
Emission Tomography/Computerized Tomography Positive Lung Mass.
PMID- 28702467
TI - Ceftaroline for Severe Methicillin-Resistant Staphylococcus aureus Infections: A
Systematic Review.
AB - Ceftaroline is approved by the Food and Drug Administration for acute bacterial
skin and skin-structure infections and community-acquired bacterial pneumonia,
including cases with concurrent bacteremia. Use for serious methicillin-resistant
Staphylococcus aureus (MRSA) infections has risen for a multitude of reasons. The
aim of this article is to review the literature evaluating clinical outcomes and
safety of ceftaroline prescribed for serious MRSA infections. We conducted a
literature search in Ovid (Medline) and PubMed for reputable case reports,
clinical trials, and reviews focusing on the use of ceftaroline for treatment of
MRSA infections. Twenty-two manuscripts published between 2010 and 2016 met
inclusion criteria. Mean clinical cure was 74% across 379 patients treated with
ceftaroline for severe MRSA infections. Toxicities were infrequent. Ceftaroline
treatment resulted in clinical and microbiologic cure for severe MRSA infections.
Close monitoring of hematological parameters is necessary with prolonged courses
of ceftaroline.
PMID- 28702468
TI - Antimicrobial Stewardship Lessons From Mupirocin Use and Resistance in
Methicillin-Resitant Staphylococcus Aureus.
AB - BACKGROUND: The quantitative relationship between antimicrobial agent consumption
and rise or fall of antibiotic resistance has rarely been studied. We began all
admission surveillance testing for methicillin-resistant Staphylococcus aureus
(MRSA) in August 2005 with subsequent contact isolation and decolonization using
nasally applied mupirocin ointment for those colonized. In October 2012, we
discontinued decolonization of medical (nonsurgical service) patients. METHODS:
We conducted a retrospective study from 2007 through 2014 of 445680 patients;
35235 were assessed because of mupirocin therapy and positive test results for
MRSA. We collected data on those patients receiving 2% mupirocin ointment for
decolonization to determine the defined daily doses (DDDs). A nonparametric
regression technique was used to quantitate the effect of mupirocin consumption
on drug resistance in MRSA. RESULTS: Using regressive modeling, we found that,
when consumption was consistently >25 DDD/1000 patient-days, there was a
statistically significant increase in mupirocin resistance with a correlating
positive rate of change. When consumption was <=25 DDD/1000 patient-days, there
was a statistically significant decrease in mupirocin resistance with a
correlating negative rate of change. The scatter plot of fitted versus observed
mupirocin resistance values showed an R2 value of 0.89-a high correlation between
mupirocin use and resistance. CONCLUSIONS: Use of the antimicrobial agent
mupirocin for decolonization had a threshold of approximately 25 DDD/1000 patient
days that separated a rise and fall of resistance within the acute-care setting.
This has implications for how widely mupirocin can be used for decolonization, as
well as for setting consumption thresholds when prescribing antimicrobials as
part of stewardship programs.
PMID- 28702469
TI - Comparison Between Carbapenems and beta-Lactam/beta-Lactamase Inhibitors in the
Treatment for Bloodstream Infections Caused by Extended-Spectrum beta-Lactamase
Producing Enterobacteriaceae: A Systematic Review and Meta-Analysis.
AB - BACKGROUND: Carbapenems are widely used for the management of bloodstream
infections (BSIs) caused by extended-spectrum beta-lactamase-producing
Enterobacteriaceae (ESBL-PE). However, the wide use of carbapenems has been
associated with carbapenem-resistant Enterobacteriaceae development. METHODS: We
searched the PubMed and Scopus databases (last search date was on June 1, 2016)
looking for studies that reported mortality in adult patients with ESBL-PE BSIs
that were treated with carbapenems or beta-lactam/beta-lactamase inhibitors
(BL/BLIs). RESULTS: Fourteen studies reported mortality data in adult patients
with ESBL-PE BSI that were treated with carbapenems or BL/BLIs. Among them, 13
studies reported extractable data on empiric therapy, with no statistically
significant difference in mortality of patients with ESBL-PE BSI that were
treated empirically with carbapenems (22.1%; 121 of 547), compared with those
that received empiric BL/BLIs (20.5%; 109 of 531; relative risk [RR], 1.05; 95%
confidence interval [CI], 0.83-1.37; I2 = 20.7%; P = .241). In addition, 7
studies reported data on definitive therapy. In total, 767 patients (79.3%)
received carbapenems and 199 patients (20.6%) received BL/BLIs as definitive
therapy, and there was again no statistically significant difference (RR, 0.62;
95% CI, 0.25-1.52; I2 = 84.6%; P < .001). Regarding specific pathogens, the use
of empiric BL/BLIs in patients with BSI due to ESBL-Escherichia coli was not
associated with a statistically significant difference in mortality (RR, 1.014;
95% CI, 0.491-2.095; I2 = 62.5%; P = .046), compared with the use of empiric
carbapenems. CONCLUSIONS: These data do not support the wide use of carbapenems
as empiric therapy, and BL/BLIs might be effective agents for initial/empiric
therapy for patients with BSI caused by likely ESBL-PE, and especially ESBL-E
coli.
PMID- 28702470
TI - Pericarditis Associated With Acute Zika Virus Infection in a Returning Traveler.
AB - Despite the widespread outbreak, few cases of Zika virus associated with cardiac
manifestations have been described. We present a case of pericarditis in the
setting of an acute, symptomatic Zika virus infection in a traveler returning
from St. Thomas. Clinicians should be alert for this potential complication of
Zika virus infection.
PMID- 28702471
TI - Erratum.
AB - [This corrects the article DOI: 10.1093/ofid/ofw221.].
PMID- 28702472
TI - Erratum.
AB - [This corrects the article DOI: 10.1093/ofid/ofw136.].
PMID- 28702473
TI - Malaria and Chikungunya Detected Using Molecular Diagnostics Among Febrile Kenyan
Children.
AB - BACKGROUND: In sub-Saharan Africa, malaria is frequently overdiagnosed as the
cause of an undifferentiated febrile illness, whereas arboviral illnesses are
presumed to be underdiagnosed. METHODS: Sera from 385 febrile Kenyan children,
who presented to 1 of 4 clinical sites, were tested using microscopy and real
time molecular assays for dengue virus (DENV), chikungunya virus (CHIKV),
malaria, and Leptospira. RESULTS: Malaria was the primary clinical diagnosis for
254 patients, and an arboviral infection (DENV or CHIKV) was the primary
diagnosis for 93 patients. In total, 158 patients (41.0%) had malaria and 32
patients (8.3%) had CHIKV infections. Compared with real-time polymerase chain
reaction, microscopy demonstrated a percent positive agreement of 49.7%. The
percentage of malaria cases detected by microscopy varied significantly between
clinical sites. Arboviral infections were the clinical diagnosis for patients on
the Indian Ocean coast (91 of 238, 38.2%) significantly more often than patients
in the Lake Victoria region (2 of 145, 1.4%; P < .001). However, detection of
CHIKV infections was significantly higher in the Lake Victoria region (19 of 145
[13.1%] vs 13 of 239 [5.4%]; P = .012). CONCLUSIONS: The clinical diagnosis of
patients with an acute febrile illness, even when aided by microscopy, remains
inaccurate in malaria-endemic areas, contributing to inappropriate management
decisions.
PMID- 28702474
TI - Targeting Visceral Fat by Intraperitoneal Delivery of Novel AAV Serotype Vector
Restricting Off-Target Transduction in Liver.
AB - It is challenging to genetically manipulate fat in adults. We demonstrate that
intraperitoneal (i.p.) injection of an engineered adeno-associated virus (AAV)
serotype Rec2 leads to high transduction of multiple visceral fat depots at a
dose of 1 to 2 orders lower than commonly used doses for systemic gene delivery.
To target adipose tissue, we develop a single AAV vector harboring two expression
cassettes: one using the CBA promoter to drive transgene expression and one using
the liver-specific albumin promoter to drive a microRNA-targeting WPRE sequence
that only exists in this AAV vector. This dual-cassette vector achieves highly
selective transduction of visceral fat while severely restricting off-target
transduction of liver. As proof of efficacy, i.p. administration of an adipose
targeting Rec2 vector harboring the leptin gene corrects leptin deficiency,
obesity, and metabolic syndromes of ob/ob mice. This study provides a powerful
tool to genetically manipulate fat for basic research and gene therapies of
genetic and acquired diseases.
PMID- 28702475
TI - Deletion of the Virion Host Shut-off Gene Enhances Neuronal-Selective Transgene
Expression from an HSV Vector Lacking Functional IE Genes.
AB - The ability of herpes simplex virus (HSV) to establish lifelong latency in
neurons suggests that HSV-derived vectors hold promise for gene delivery to the
nervous system. However, vector toxicity and transgene silencing have created
significant barriers to vector applications to the brain. Recently, we described
a vector defective for all immediate-early gene expression and deleted for the
joint region between the two unique genome segments that proved capable of
extended transgene expression in non-neuronal cells. Sustained expression
required the proximity of boundary elements from the latency locus. As confirmed
here, we have also found that a transgene cassette introduced into the ICP4 locus
is highly active in neurons but silent in primary fibroblasts. Remarkably, we
observed that removal of the virion host shutoff (vhs) gene further improved
transgene expression in neurons without inducing expression of viral genes. In
rat hippocampus, the vhs-deleted vector showed robust transgene expression
exclusively in neurons for at least 1 month without evidence of toxicity or
inflammation. This HSV vector design holds promise for gene delivery to the
brain, including durable expression of large or complex transgene cassettes.
PMID- 28702477
TI - The case for autoimmune neurology.
PMID- 28702476
TI - Regulatable Transgene Expression for Prevention of Chemotherapy-Induced
Peripheral Neuropathy.
AB - Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating complication
associated with drug treatment of cancer for which there are no effective
strategies of prevention or treatment. In this study, we examined the effect of
intermittent expression of neurotophin-3 (NT-3) or interleukin-10 (IL-10) from
replication-defective herpes simplex virus (HSV)-based regulatable vectors
delivered by subcutaneous inoculation to the dorsal root ganglion (DRG) on the
development of paclitaxel-induced peripheral neuropathy. We constructed two
different tetracycline (tet)-on-based regulatable HSV vectors, one expressing NT
3 and the other expressing IL-10, in which the transactivator expression in the
tet-on system was under the control of HSV latency-associated promoter 2 (LAP-2),
and expression of the transgene was controlled by doxycycline (DOX). We examined
the therapeutic effect of intermittent expression of the transgene in animals
with paclitaxel-induced peripheral neuropathy modeled by intraperitoneal
injection of paclitaxel (16 mg/kg) once a week for 5 weeks. Intermittent
expression of either NT-3 or IL-10 3 days before and 1 day after paclitaxel
administration protected animals against paclitaxel-induced peripheral neuropathy
over the course of 5 weeks. These results suggest the potential of regulatable
vectors for prevention of chemotherapy-induced peripheral neuropathy.
PMID- 28702478
TI - Emerging roles of microglia cells in the regulation of adult neural stem cells.
AB - Microglia cells were first described as a component for the brain with few
beneficial functions. The classical point of view implied that these cells had
inflammatory properties more than benefits for brain homeostasis. To date, this
assumption has changed and new roles of microglia cells are continuously
discovered. Although, the main function of microglia cells is to provide a
cellular defense against harmful or pathogen agents (bacteria, viruses, fungi,
toxins, etc.), recent evidence indicates that microglial cells are dynamic
modulators of synaptic pruning, brain development and neurogenesis by maintaining
a balance of local cell population. In this commentary, we summarized the
emerging role of the relationship between microglia cells and the neural stem
cells resident in the ventricular-subventricular zone (V-SVZ), the largest
neurogenic niche in the adult brain.
PMID- 28702479
TI - Image quality and contrast agent exposure in cardiac computed tomography
angiography prior to transcatheter aortic valve implantation procedures using
different acquisition protocols.
AB - BACKGROUND: ECG-gated cardiac computed tomography angiography (CCTA) has found
widespread use for prosthesis sizing before transcatheter aortic valve
implantation (TAVI). However, still little data exists on the optimal scan
strategy in such patients. We hypothesized that prospectively triggered CCTA can
enable the visualization of aortic valve structures and peripheral arteries with
lower radiation and contrast agent exposure in patients considered for TAVI
compared to retrospectively gated protocols. METHODS: All studies were performed
using a 256 multi-detector single source CT (iCT Philips, Best, Netherlands).
With the prospective protocol the whole volume from the heart to the iliofemoral
arteries scanned using prospective triggering. With the retrospective protocol a
first retrospectively gated scan was performed for the heart and the iliofemoral
part was subsequently scanned using a second non-triggered scan. Image quality
was assessed semi-quantitatively and signal-to-noise- (SNR) and contrast-to-noise
ratios (CNR) were obtained for all scans. RESULTS: Prospective CCTA was performed
in 74 and in 34 patients, respectively using non-tailored and BMI adapted scans,
whereas retrospective CCTA was performed in 57 patients. Prospective scans
required lower contrast agent administration compared to retrospective scans (71
+/- 8 mL versus 91 +/- 15 mL, p < 0.01) and resulted in lower radiation exposure
(26 +/- 7mSv for retrospective versus 15 +/- 3mSv for non-tailored prospective
versus 8 +/- 4mSv for BMI-adapted prospective scans, p < 0.01). Visual image
quality was better for the evaluation of aortic valve structures and similar for
the assessment of iliofemoral anatomy with prospective versus retrospective
scans. In addition, contrast density, SNR and CNR were higher in the ascending
aorta with prospective versus retrospective CCTA (434 +/- 98HU versus 349 +/-
112HU; 35 +/- 14 versus 24 +/- 9 and 31 +/- 11 versus 16 +/- 7, p < 0.001 for
all). Subsection analysis by heart rate groups demonstrated that both image
quality and CNR were significantly higher in patients with prospective versus
retrospective CCTA, irrespective of the heart rate during image acquisition.
CONCLUSION: Prospectively triggered CCTA allows for improved visualization of
aortic valve structures and peripheral arteries in patients scheduled for TAVI
with simultaneously reduced contrast agent dose and radiation exposure.
Therefore, this acquisition mode seems to be the preferred for the evaluation of
patients considered for TAVI.
PMID- 28702480
TI - Dataset on transcriptional profiles and the developmental characteristics of
PDGFRalpha expressing lung fibroblasts.
AB - The following data are derived from key stages of acinar lung development and
define the developmental role of lung interstitial fibroblasts expressing
platelet-derived growth factor alpha (PDGFRalpha). This dataset is related to the
research article entitled "Temporal, spatial, and phenotypical changes of
PDGFRalpha expressing fibroblasts during late lung development" (Endale et al.,
2017) [1]. At E16.5 (canalicular), E18.5 (saccular), P7 (early alveolar) and P28
(late alveolar), PDGFRalphaGFP mice, in conjunction with immunohistochemical
markers, were utilized to define the spatiotemporal relationship of PDGFRalpha+
fibroblasts to endothelial, stromal and epithelial cells in both the proximal and
distal acinar lung. Complimentary analysis with flow cytometry was employed to
determine changes in cellular proliferation, define lipofibroblast and
myofibroblast populations via the presence of intracellular lipid or alpha smooth
muscle actin (alphaSMA), and evaluate the expression of CD34, CD29, and Sca-1.
Finally, PDGFRalpha+ cells isolated at each stage of acinar lung development were
subjected to RNA-Seq analysis, data was subjected to Bayesian timeline analysis
and transcriptional factor promoter enrichment analysis.
PMID- 28702481
TI - Data on body weight and liver functionality in aged rats fed an enriched
strawberry diet.
AB - Here, we present new original data on the effects of strawberry consumption on
body weight and liver status of aged rats. Wistar rats aged 19-21 months were fed
a strawberry enriched diet prepared by substituting 15% of the total calories
with freeze-dried strawberry powder for two months. Body weight, plasma
biomarkers of liver injury (alanine transferase, aspartate aminotransferase and
alkaline phosphatase) and liver histological analysis were assessed. These data
indicate that strawberry supplementation did not interfere with normal animal
maintenance and with liver structure and functionality. For further details and
experimental findings please refer to the article "Strawberry consumption
improves aging-associated impairments, mitochondrial biogenesis and functionality
through the AMP-Activated Protein Kinase signaling cascade" in FOOD CHEMISTRY
(Giampieri et al., 2017) [1].
PMID- 28702482
TI - Visualization of simulated small vessels on computed tomography using a model
based iterative reconstruction technique.
AB - This article describes a quantitative evaluation of visualizing small vessels
using several image reconstruction methods in computed tomography. Simulated
vessels with diameters of 1-6 mm made by 3D printer was scanned using 320-row
detector computed tomography (CT). Hybrid iterative reconstruction (hybrid IR)
and model-based iterative reconstruction (MBIR) were performed for the image
reconstruction.
PMID- 28702483
TI - Datasets for supplier selection and order allocation with green criteria, all
unit quantity discounts and varying number of suppliers.
AB - This data article provides detailed optimization input and output datasets and
optimization code for the published research work titled "Dynamic green supplier
selection and order allocation with quantity discounts and varying supplier
availability" (Hamdan and Cheaitou, 2017, In press) [1]. Researchers may use
these datasets as a baseline for future comparison and extensive analysis of the
green supplier selection and order allocation problem with all-unit quantity
discount and varying number of suppliers. More particularly, the datasets
presented in this article allow researchers to generate the exact optimization
outputs obtained by the authors of Hamdan and Cheaitou (2017, In press) [1] using
the provided optimization code and then to use them for comparison with the
outputs of other techniques or methodologies such as heuristic approaches.
Moreover, this article includes the randomly generated optimization input data
and the related outputs that are used as input data for the statistical analysis
presented in Hamdan and Cheaitou (2017 In press) [1] in which two different
approaches for ranking potential suppliers are compared. This article also
provides the time analysis data used in (Hamdan and Cheaitou (2017, In press) [1]
to study the effect of the problem size on the computation time as well as an
additional time analysis dataset. The input data for the time study are generated
randomly, in which the problem size is changed, and then are used by the
optimization problem to obtain the corresponding optimal outputs as well as the
corresponding computation time.
PMID- 28702484
TI - Data on the anisotropic interfacial slip length over fibrous porous media.
AB - To characterize the velocity slip at the fibrous porous media, data on the
anisotropic slip length has been fully analyzed through direct simulations for
various geometrical aspects of fiber architecture [2] ). This data article
provides detailed slip lengths and slip coefficients in dimensionless form as a
function of various geometrical parameters of fibrous porous media including the
fiber volume fraction, the dimensionless void length and the normalized
permeability. The data is presented for three different fiber packing structures
(the quadrilateral, hexagonal and compressed hexagonal packing) in both the fiber
and normal to fiber directions. Finally a set of curves from the complete fitted
equation set are also provided in a single figure that can be used to estimate
the slip length and the normalized permeability for a given fibrous porous media.
PMID- 28702485
TI - Experimental data on the properties of natural fiber particle reinforced polymer
composite material.
AB - This paper presents an experimental study on the development of polymer bio
composites. The powdered coconut shell, walnut shells and Rice husk are used as
reinforcements with bio epoxy resin to form hybrid composite specimens. The fiber
compositions in each specimen are 1:1 while the resin and hardener composition
10:1 respectively. The fabricated composites were tested as per ASTM standards to
evaluate mechanical properties such as tensile strength, flexural strength, shear
strength and impact strength are evaluated in both with moisture and without
moisture. The result of test shows that hybrid composite has far better
properties than single fibre glass reinforced composite under mechanical loads.
However it is found that the incorporation of walnut shell and coconut shell
fibre can improve the properties.
PMID- 28702486
TI - Survey datasets on the externalizing behaviors of primary school pupils and
secondary school students in some selected schools in Ogun State, Nigeria.
AB - This data article contains the partial analysis (descriptive statistics) of data
obtained from 1770 primary school pupils and secondary school students in three
Local Government Areas of Ogun State, Nigeria. The schools are either privately
owned or public (government owned) schools. The aim of the field survey is to
measure the level and patterns of externalizing behavior of the respondents. The
data was collected using a standardized questionnaire. The questionnaire is a
modification of Achenbach manual for Child behavior checklist (Achenbach, 2001)
[1] and manual for Youth self-report (Achenbach and Rescorla, 2001) [2]. The
questionnaire was designed to suit the demographic and socio-cultural nature of
the target population. Analysis of the data can provide useful insights to the
patterns of externalizing behavior of primary school pupils and secondary school
students.
PMID- 28702487
TI - Dataset on lipid profile of bovine oocytes exposed to Lalpha-phosphatidylcholine
during in vitro maturation investigated by MALDI mass spectrometry and gas
chromatography-flame ionization detection.
AB - Data presented in this article are related with the research article entitled
"Effect of soybean phosphatidylcholine on lipid profile of bovine oocytes matured
in vitro" [1]. This article describes the differences in the relative abundance
of the lipid ions detected by matrix-assisted laser desorption/ionization mass
spectrometry (MALDI-MS) in control and Lalpha-phosphatidylcholine-treated
oocytes. In addition, the fatty acids (FA) content in pure Lalpha
phosphatidylcholine supplement and oocytes was analyzed by gas chromatography
flame ionization detection (GC-FID). The dataset provides information and inputs
for further studies aiming to optimize in vitro maturation conditions and
cryotolerance of mammalian oocytes.
PMID- 28702488
TI - Data on the physical and mechanical properties of soilcrete materials modified
with metakaolin.
AB - During the last decades eco-friendly, low-cost, sustainable construction
materials for utilization in civil engineering projects have attracted much
attention. To this end, soilcretes are non-conventional construction materials
produced by mixing natural soil such as natural clay or limestone sand with a
hydraulic binder and are recently under detailed and in-depth investigation by
many researchers. In this paper the results of the physical and mechanical
characteristics of a large set of cylindrical specimens under uniaxial
compression, are presented. Specifically, two types of soils such as sand and
clay with metakaolin as a mineral additive have been used. This database can be
extremely valuable for better understanding of the behavior of soilcrete
materials. Furthermore, the results presented herein expected to be of great
interest for researchers who deal with the prediction of mechanical properties of
materials using soft computing techniques such as artificial intelligence (AI)
techniques.
PMID- 28702489
TI - Data on the effect of in utero exposure to polycyclic aromatic hydrocarbons on
genome-wide patterns of DNA methylation in lung tissues.
AB - Data in this article depict patterns of methylation in lung tissues obtained from
the offspring of B6129SF1/J dams and 129S1/SvImJ sires exposed in utero to
benzo[a]pyrene (BaP) or dibenzo[def,p]chrysene (DBC) as compared to non-exposed
offspring. Genome-wide methylation of lung tumors in adult offspring was
determined using methylated DNA immunoprecipitation (MeDIP) with the NimbleGen
mouse DNA methylation CpG island array. This data article refers to the research
article "DNA methylation in lung tissues of mouse offspring exposed in utero to
polycyclic aromatic hydrocarbons," [1] in which comprehensive data interpretation
and analysis are provided.
PMID- 28702490
TI - Sigma-2 receptor ligands QSAR model dataset.
AB - The data have been obtained from the Sigma-2 Receptor Selective Ligands Database
(S2RSLDB) and refined according to the QSAR requirements. These data provide
information about a set of 548 Sigma-2 (sigma2) receptor ligands selective over
Sigma-1 (sigma1) receptor. The development of the QSAR model has been undertaken
with the use of CORAL software using SMILES, molecular graphs and hybrid
descriptors (SMILES and graph together). Data here reported include the
regression for sigma2 receptor pKi QSAR models. The QSAR model was also employed
to predict the sigma2 receptor pKi values of the FDA approved drugs that are
herewith included.
PMID- 28702491
TI - Data on the time of integration of the human mitochondrial pseudogenes (NUMTs)
into the nuclear genome.
AB - The data and methods presented in this article are supplementing the research
article "Integration of mtDNA pseudogenes into the nuclear genome coincides with
speciation of the human genus. A hypothesis", DOI: 10.1016/j.mito.2016.12.001
(Gunbin et al., 2017) [1]. Mitochondrial DNA is known to get inserted into
nuclear DNA to form NUMTs, i.e. nuclear DNA pseudogenes of the mtDNA. We present
here the sequences of selected NUMTs, in which time of integration can be
determined with sufficient precision. We report their chromosomal positions ,
their position within the great ape mtDNA phylogeny, and their times of
integration into the nuclear genome. The methods used to generate the data and to
control their quality are also presented. The dataset is made publicly available
to enable critical or extended analyzes.
PMID- 28702492
TI - Advanced treatment of saline municipal wastewater by Ruppia maritima: A data set.
AB - Saline municipal wastewater treatment is a challenging environmental issue in
coastal cities, due to the discharge of saline water into the sewers. The present
research article focuses on the phytoremediation of high saline municipal
wastewater by Ruppia maritime, a widespread plant which can be found in saline
medium such as traditional fish ponds, estuaries, tidal flats, salt pans, coastal
paddy fields, coastal lagoons, marsh pools, and mangrove salt marshes in
Khuzestan province, Iran. The experimental data was obtained using a pilot plant
constructed in Chobeineh wastewater treatment plant in Ahvaz city, fed by
activated sludge effluent in 3 levels of electrical conductivity (EC) (10, 15, 20
ms cm-1), during 45 days of the experiment. Chemical oxygen demand (COD), total
nitrogen (TN), total phosphorus (TP) and total suspended solids (TSS) were daily
monitored in blank and pilot study. The COD removal decreased from 83.26% to
72.39% by increasing the EC level from 10 to 20 ms cm-1, respectively. The
experimental data will practically be an appropriate source of information for
environmental engineers to design a natural treatment scenario for saline
wastewater treatment.
PMID- 28702493
TI - Data on the effect of sex on the size, cellular content, and neuronal density of
the developing brain in mice exposed to isoflurane and carbon monoxide.
AB - The data presented here detail the changes in size, cellular content, and
neuronal density of the developing brain over time with respect to sex in C57Bl/6
mice following neonatal exposure to isoflurane, carbon monoxide, or their
combination. Specifically, brain weight- and brain volume-to-body weight ratios
are presented, representative immunoblots of whole brain cell-specific protein
content are depicted, and quantification of the number of neurons in the primary
somatosensory cortex and CA3 region of the hippocampus are shown. Three discrete
postnatal time points are represented: P7 (prior to exposure), P14 (one-week post
exposure), and P42-56 (5-7 weeks post exposure). Major findings from the data
presented here are reported in the manuscript "Carbon Monoxide Incompletely
Prevents Isoflurane-induced Defects in Murine Neurodevelopment" (Wang et al., in
press) [1].
PMID- 28702494
TI - Accessibility and usability OCW data: The UTPL OCW.
AB - This data article provides a data description on article entitled "A framework
for improving web accessibility and usability of Open Course Ware sites" [3] This
Data in Brief presents the data obtained from the accessibility and usability
evaluation of the UTPL OCW. The data obtained from the framework evaluation
consists of the manual evaluation of the standards criteria and the automatic
evaluation of the tools Google PageSpeed and Google Analytics. In addition, this
article presents the synthetized tables from standards that are used by the
framework to evaluate the accessibility and usability of OCW, and the
questionnaires required to extract the data. As a result, the article also
provides the data required to reproduce the evaluation of other OCW.
PMID- 28702495
TI - Data on Leptospira interrogans sv Pomona infection in Meat Workers in New
Zealand.
AB - The data presented in this article are related to the research article entitled
"Comparison between Generalized Linear Modelling and Additive Bayesian Network;
Identification of Factors associated with the Incidence of Antibodies against
Leptospira interrogans sv Pomona in Meat Workers in New Zealand" (Pittavino et
al., 2017) [5]. A prospective cohort study was conducted in four sheep
slaughtering abattoirs in New Zealand (NZ) (Dreyfus et al., 2015) [1]. Sera were
collected twice a year from 384 meat workers and tested by Microscopic
Agglutination for Leptospira interrogans sv Pomona (Pomona) infection, one of the
most common Leptospira serovars in humans in NZ. This article provides an
extended analysis of the data, illustrating the different steps of a
multivariable (i.e. generalized linear model) and especially a multivariate tool
based on additive Bayesian networks (ABN) modelling.
PMID- 28702496
TI - Nasal septal and mucosal disease associated with pyoderma gangrenosum in a
cocaine user.
PMID- 28702497
TI - Mycosis fungoides presenting as symmetric concentric patches mimicking figurate
erythema.
PMID- 28702498
TI - Leukocytoclastic vasculitis in transplant recipients: A case series of 7
patients.
PMID- 28702499
TI - Metastasis of cervical cancer to breast: A case report and review of literature.
AB - Metastasis to the breast from an extra-mammary malignancy has been documented in
literature, however cervical cancer metastasis to the breast is very rare. Thirty
eight cases of metastatic deposit to the breast from cervical cancer have been
reported in literature. Though most patients present with a breast lump, it is
very difficult to clinically distinguish a primary breast malignancy from a
metastatic deposit. Histopathology of the tissue, aided with immune-histochemical
staining pattern provides a definitive diagnosis. Our patient, a 51-year old
woman presented with breast lump and history of post-menopausal bleeding. Upon
further workup, the patient was diagnosed with cervical cancer. The mammogram and
ultrasound of the breast showed multiple lumps within the breast. Histopathology
of the breast mass showed metastatic deposit in the breast from cervical cancer.
The patient was treated with radiation therapy to the cervix along with
concurrent chemotherapy for local control of pain. After completion of local
treatment, she started systemic chemotherapy, however she developed health-care
associated pneumonia and subdural hematoma leading to deterioration in her
performance status. The patient opted for hospice care and died 2 months later.
In this report, we will review the presentation of the 38 cases reported in
literature and the imaging and histopathologic findings of metastatic deposits to
the breast.
PMID- 28702500
TI - Surgical management of a large neurilemmoma-like leiomyoma of the uterine cervix
mimicking a retroperitoneal tumor.
AB - *A large cervical neurilemmoma-like leiomyoma can simulate a retroperitoneal
tumor.*They are extremely rare tumors that require adequate bleeding
control.*Comprehensive anatomo-pathological study should be done to rule out
malignancy.
PMID- 28702501
TI - Patterns of cervical cancer care in Argentina: Applying ASCO recommendations
adjusted by local resources.
AB - There are significant differences in cervical cancer incidence and mortality
between low-middle and high-income countries. The American Society of Clinical
Oncology (ASCO) resource-stratified clinical practice guideline was designed to
provide an appropriate cervical cancer treatment based on the best available
evidence in scenarios with different diagnostic and therapeutic resources.
Argentina, a Latin American high middle income country, shows however, that
cervical cancer rates are similar to those of low-income countries. In addition,
significant disparities in incidence and mortality are described throughout the
country. The present article describes the current pattern of care of cervical
cancer in Argentina and establishes recommendations adjusted to local resources
in different regions of the country according to the ASCO guideline.
PMID- 28702502
TI - Characteristics and Clinical Outcomes in Overhead Sports Athletes after Rotator
Cuff Repair.
AB - Rotator cuff tears in young overhead sports athletes are rare. The pathomechanism
causing rotator cuff tears in young overhead athletes is different from that in
aged patients. The purpose of this study was to investigate rotator cuff tear
characteristics in young overhead sports athletes to reveal the pathomechanism
causing these injuries. This study included 25 overhead sports athletes less than
30 years old with atraumatic rotator cuff tears necessitating repair. Rotator
cuff tear characteristics were evaluated intraoperatively, including rotator cuff
tear shape and injured rotator cuff tendon. Clinical outcome measures were
assessed before surgery and at the final follow-up. In this study, 22 patients
reported minimal to no shoulder pain and returned to sports without significant
complaints at last follow-up. The isolated infraspinatus tendon was most often
injured; the incidence rate of the tear at this site was 32% (8 cases). In the
deceleration phase of overhead motion, the eccentric contraction force of the ISP
(infraspinatus) tendon peaks and the increased load leads to injury at the ISP
tendon. The pathomechanism of rotator cuff injuries in young overhead athletes
might be not only internal or subacromial impingement, but also these mechanisms.
PMID- 28702503
TI - Strong and Flexible: Developing a Three-Tiered Curriculum for the Regional
Central America Field Epidemiology Training Program.
AB - Field Epidemiology Training Programs (FETPs) are recognized worldwide as an
effective means to strengthen countries' capacity in epidemiology, surveillance,
and outbreak response. FETPs are field-based, with minimum classroom time and
maximum time in the field, providing public health services while participants
achieve competency. The Central America FETP (CAFETP) uses a three-level pyramid
model: basic, intermediate, and advanced. In 2006, a multidisciplinary team used
a methodical process based on adult learning practices to construct a competency
based curriculum for the CAFETP. The curriculum was designed based on the tasks
related to disease surveillance and field epidemiology that public health
officers would conduct at multiple levels in the system. The team used a design
process that engaged subject matter experts and considered the unique perspective
of each country. The designers worked backwards from the competencies to define
field activities, evaluation methods, and classroom components. The 2006 pyramid
curriculum has been accredited for a master's of science in field epidemiology by
the Universidad del Valle de Guatemala and has been adapted by programs around
the world. The team found the time and effort spent to familiarize subject matter
experts with key adult learning principles was worthwhile because it provided a
common framework to approach curriculum design. Early results of the redesigned
curriculum indicate that the CAFETP supports consistent quality while allowing
for specific country needs.
PMID- 28702504
TI - Response inhibition in Parkinson's disease: a meta-analysis of dopaminergic
medication and disease duration effects.
AB - Parkinson's disease is a neurodegenerative disorder involving the basal ganglia
that results in a host of motor and cognitive deficits. Dopamine-replacement
therapy ameliorates some of the hallmark motor symptoms of Parkinson's disease,
but whether these medications improve deficits in response inhibition, a critical
executive function for behavioral control, has been questioned. Several studies
of Parkinson's disease patients "on" and "off" (12-h withdrawal) dopaminergic
medications suggested that dopamine-replacement therapy did not provide
significant response inhibition benefits. However, these studies tended to
include patients with moderate-to-advanced Parkinson's disease, when the efficacy
of dopaminergic drugs is reduced compared to early-stage Parkinson's disease. In
contrast, a few recent studies in early-stage Parkinson's disease report that
dopaminergic drugs do improve response inhibition deficits. Based on these
findings, we hypothesized that Parkinson's disease duration interacts with
medication status to produce changes in cognitive function. To investigate this
issue, we conducted a meta-analysis of studies comparing patients with
Parkinson's disease and healthy controls on tests of response inhibition (50
comparisons from 42 studies). The findings supported the hypothesis; medication
benefited response inhibition in patients with shorter disease duration, whereas
"off" medication, moderate deficits were present that were relatively unaffected
by disease duration. These findings support the role of dopamine in response
inhibition and suggest the need to consider disease duration in research of the
efficacy of dopamine-replacement therapy on cognitive function in Parkinson's
disease.
PMID- 28702505
TI - Human snoRNA-93 is processed into a microRNA-like RNA that promotes breast cancer
cell invasion.
AB - Genetic searches for tumor suppressors have recently linked small nucleolar RNA
misregulations with tumorigenesis. In addition to their classically defined
functions, several small nucleolar RNAs are now known to be processed into short
microRNA-like fragments called small nucleolar RNA-derived RNAs. To determine if
any small nucleolar RNA-derived RNAs contribute to breast malignancy, we recently
performed a RNA-seq-based comparison of the small nucleolar RNA-derived RNAs of
two breast cancer cell lines (MCF-7 and MDA-MB-231) and identified small
nucleolar RNA-derived RNAs derived from 13 small nucleolar RNAs overexpressed in
MDA-MB-231s. Importantly, we find that inhibiting the most differentially
expressed of these small nucleolar RNA-derived RNAs (sdRNA-93) in MDA-MB-231
cells results primarily in a loss of invasiveness, whereas increased sdRNA-93
expression in either cell line conversely results in strikingly enhanced
invasion. Excitingly, we recently determined sdRNA-93 expressions in small RNA
seq data corresponding to 116 patient tumors and normal breast controls, and
while we find little sdRNA-93 expression in any of the controls and only sporadic
expression in most subtypes, we find robust expression of sdRNA-93 in 92.8% of
Luminal B Her2+tumors. Of note, our analyses also indicate that at least one of
sdRNA-93's endogenous roles is to regulate the expression of Pipox, a sarcosine
metabolism-related protein whose expression significantly correlates with
distinct molecular subtypes of breast cancer. We find sdRNA-93 can regulate the
Pipox 3'UTR via standard reporter assays and that manipulating endogenous sdRNA
93 levels inversely correlates with altered Pipox expression. In summary, our
results strongly indicate that sdRNA-93 expression actively contributes to the
malignant phenotype of breast cancer through participating in microRNA-like
regulation.
PMID- 28702506
TI - Prenatal Depression Risk Factors, Developmental Effects and Interventions: A
Review.
AB - This narrative review based on a literature search in PubMed and PsycInfo on the
two terms prenatal and antenatal depression includes empirical studies, reviews
and meta-analyses that have been published during the last 5 years on risk
factors, developmental effects and interventions for prenatal depression. Risk
factor studies that met criteria feature demographic measures (lower
socioeconomic status, less education, non-marital status, non-employment, less
social support and health locus of control, unintended pregnancy, partner
violence and history of child abuse) and physiological variables (cortisol,
amylase, and pro-inflammatory cytokines and intrauterine artery resistance). The
negative effects include postpartum depression, paternal depression, and
prematurity and low birth weight. Negative effects on infants include greater
right frontal EEG, amygdala connectivity, cortical thinning and more difficult
temperament. In childhood, externalizing and internalizing problems have been
reported. The data on prenatal antidepressants (specifically SSRIs) reveal
negative effects including internalizing problems as well as a greater risk for
autism spectrum disorder. Prenatal interventions that have been effective include
interpersonal psychotherapy, peer support, massage therapy, yoga, tai chi, and
aerobic exercise. Potential underlying mechanisms are discussed as well as
methodological limitations including homogeneity of samples and lack of
randomization to intervention groups. Despite these limitations, the literature
highlights the need for prenatal depression screening and intervention.
PMID- 28702507
TI - Brainstem phenotype of cathepsin A-related arteriopathy with strokes and
leukoencephalopathy.
PMID- 28702508
TI - Homozygous mutation in HSPB1 causing distal vacuolar myopathy and motor
neuropathy.
PMID- 28702509
TI - Loss-of-function variants of SCN8A in intellectual disability without seizures.
AB - OBJECTIVE: To determine the functional effect of SCN8A missense mutations in 2
children with intellectual disability and developmental delay but no seizures.
METHODS: Genomic DNA was analyzed by next-generation sequencing. SCN8A variants
were introduced into the Nav1.6 complementary DNA by site-directed mutagenesis.
Channel activity was measured electrophysiologically in transfected ND7/23 cells.
The stability of the mutant channels was assessed by Western blot. RESULTS: Both
children were heterozygous for novel missense variants that altered conserved
residues in transmembrane segments of Nav1.6, p.Gly964Arg in D2S6 and
p.Glu1218Lys in D3S1. Both altered amino acids are evolutionarily conserved in
vertebrate and invertebrate channels and are predicted to be deleterious. Neither
was observed in the general population. Both variants completely prevented the
generation of sodium currents in transfected cells. The abundance of Nav1.6
protein was reduced by the Glu1218Lys substitution. CONCLUSIONS:
Haploinsufficiency of SCN8A is associated with cognitive impairment. These
observations extend the phenotypic spectrum of SCN8A mutations beyond their
established role in epileptic encephalopathy (OMIM#614558) and other seizure
disorders. SCN8A should be considered as a candidate gene for intellectual
disability, regardless of seizure status.
PMID- 28702511
TI - Variation in the Zinc Finger of PRDM9 is Associated with the Absence of
Recombination along Nondisjoined Chromosomes 21 of Maternal Origin.
AB - Variation in the zinc finger-binding domain (ZFBD) of the protein PR Domain
Containing Protein 9 (PRDM9) is associated with altered placement of
recombination in the human genome. As both the absence and altered placement of
recombination are observed among chromosomes 21 that nondisjoin, we genotyped the
PRDM9 ZFBD among mothers of children with Trisomy 21 in efforts to determine if
variation within this region is associated with the recombination-related risk
for chromosome 21 nondisjunction (NDJ). In our approach, PCR was used to amplify
the ZFBD of PRDM9 and products were then subjected to bi-directional Sanger
sequencing. DNA sequencing reads were aligned and compared to the sequence of the
PRDM9 alleles previously identified. Chi-Square analysis was used to compare
allele frequencies between cases (N=235, mothers of children with maternally
derived Trisomy 21) and controls (N=48, fathers of children with maternally
derived Trisomy 21). Results of our analysis showed that the frequency of PRDM9
ZF minor alleles is significantly increased among women displaying NDJ of
chromosome 21 and no recombination on 21q (p=0.02). Even more, when compared to
those for the PRDM9 major A-allele, these minor alleles displayed fewer predicted
binding sites on 21q. These findings suggest that allelic variation in the ZF of
PRDM9 may play a role in the risk for chromosome 21 NDJ by leading to reduced
recombination on 21q.
PMID- 28702512
TI - A Fully Implantable, NFC Enabled, Continuous Interstitial Glucose Monitor.
AB - This work presents an integrated system-on-chip (SoC) that forms the core of a
long-term, fully implantable, battery assisted, passive continuous glucose
monitor. It integrates an amperometric glucose sensor interface, a near field
communication (NFC) wireless front-end and a fully digital switched mode power
management unit for supply regulation and on board battery charging. It uses
13.56 MHz (ISM) band to harvest energy and backscatter data to an NFC reader.
System was implemented in 14nm CMOS technology and validated with post layout
simulations.
PMID- 28702513
TI - An Auditory Nerve Stimulation Chip with Integrated AFE, Sound Processing, and
Power Management for Fully Implantable Cochlear Implants.
AB - This paper presents a system on chip for a fully implantable cochlear implant. It
includes acoustic sensor front-end, 4-channel digital sound processing and
auditory nerve stimulation circuitry. It also features a digital, switched mode,
single inductor dual output power supply that generates two regulated voltages;
0.4 V used to supply on-chip digital blocks and 0.9 V to supply analog blocks and
charge the battery when an external RF source is detected. All passives are
integrated on-chip including the inductor. The system was implemented in 14nm
CMOS and validated with post layout simulations.
PMID- 28702514
TI - Emerging Role of the Cerebrospinal Fluid - Neuronal Interface in Neuropathology.
AB - The choroid plexus and cerebrospinal fluid have recently begun to emerge as
essential regulators of neural function. Factors produced by the choroid plexus
are released into the ventricular environment and thus provide a rich source of
extracellular signaling molecules throughout the central nervous system.
Identified factors in the cerebrospinal fluid include growth factors, hormones,
proteins, peptides, lipids, glucose, microRNAs (miRNAs), messenger RNA (mRNA),
and enzymes. In addition to mediating neural function, these factors have the
potential to serve as biomarkers of disease states. In this review, we highlight
recent advances demonstrating the importance of extracellular signaling
mechanisms in mediating neural function and provide recent evidence for their
role in neuropathology.
PMID- 28702515
TI - Chemoselective Ullmann coupling at room temperature: a facile access to 2
aminobenzo[b]thiophenes.
AB - Various functionalized 2-aminobenzo[b]thiophenes have been synthesized at room
temperature by the Ullmann coupling reaction for the first time. The
enantiospecific coupling reaction has been further demonstrated without loss of
optical purity. The newly synthesized 2-anilino-3-cyano-benzo[b]thiophenes are
transformed into 11-amino-benzothieno[2,3-b]quinolines in the presence of triflic
acid.
PMID- 28702516
TI - Enhancement of the upconversion photoluminescence of hexagonal phase
NaYF4:Yb3+,Er3+ nanoparticles by mesoporous gold films.
AB - Efficient enhancement of photoluminescence in rare-earth activated upconversion
materials is of great significance for their practical applications in various
fields. In this work, three-dimensional mesoporous gold films were fabricated by
a low-cost and facile dealloying approach to improve the upconversion
photoluminescence efficiency. The mesoporous Au films exhibit good chemical
stability, large-area uniformity and abundant distribution of porous nanospaces.
Varying the time of the dealloying process leads to modification of the pore size
distribution, surface roughness and residual Ag content, resulting in effective
tuning of the wavelength of the broadband localized surface plasmon resonance
(LSPR). Enhancement factors were identified to be a function of the dealloying
time. With the optimized upconversion photoluminescence enhancement, a 41-fold
increase was achieved with the mesoporous gold substrate which had been dealloyed
for 8 days. These results pave the way to overcome the limitation of poor
upconversion efficiency for widespread practical applications in life science and
energy fields.
PMID- 28702517
TI - Fundamental chemistry of binary S,N and ternary S,N,O anions: analogues of sulfur
oxides and N,O anions.
AB - Binary S,N anions, e.g., NSN2- and SSNSS-, and related ternary S,N,O anions such
as the structural isomers NSO-/SNO- and SSNO- are rarely mentioned in inorganic
chemistry textbooks, despite the fact that their salts were synthesised and
structurally characterised more than 30 years ago. These fundamentally important
species and their conjugate acids, e.g. HNSO and HSNO, have been the focus of
numerous investigations in recent years in view of their significance in
disciplines as diverse as atmospheric chemistry and cell biology. This Tutorial
Review provides a consolidated account of the fundamental chemistry including
synthesis, spectroscopic characterisation, molecular and electronic structures,
and properties of these intriguing species, and compares these aspects of their
behaviour with those of isoelectronic sulfur oxides and N,O anions. A final
section draws attention to the significance and applications of these simple S-N
species in a broader context.
PMID- 28702518
TI - Colloidal particles with complex microstructures via phase separation in swelled
polymer microspheres.
AB - Polymer microparticles with complex microstructures, including cut spheres, bowl
like particles, hollow spheres with holes and porous hollow spheres, were
prepared via phase separation in polymer microspheres. The incorporation of
sulfonic acid groups is crucial, and the resulting microparticles are in sharp
contrast to those prepared from regular polystyrene microspheres.
PMID- 28702519
TI - Bottom-up hydrogen deuterium exchange mass spectrometry: data analysis and
interpretation.
AB - Hydrogen Deuterium Exchange (HDX) Mass Spectrometry (MS) is a sensitive
analytical technique that provides information on protein conformation and
dynamics in solution. It is commonly used in the study of protein-ligand and
protein-protein interactions and more recently in the pharmaceutical industry for
epitope mapping, screening drug candidates and in the comparison of
biopharmaceuticals to biosimilars. HDX-MS monitors the exchange of protein
backbone hydrogen atoms with deuterium in solution. Recent advancements in HDX
automation and data analysis, have taken the emphasis off developing a
fundamental understanding of HDX, which is still lacking. This tutorial review
will cover the different mechanisms of exchange and how the exchange reaction is
affected by various factors. We also explore the basis of data analysis and the
difficulties that often arise in the interpretation of site-specific and segment
averaged HDX data, such as overlapping isotopic distributions and correct
identification of peptides. Initial data analysis generates a list of peptides
and the deuterium incorporation of each peptide at each labeling time point,
i.e., a set of deuterium uptake profiles. Data interpretation and error analysis
is subsequently required to ensure that deuterium uptake profiles accurately
reflect conformational dynamics in solution. Finally, this review will also
discuss the different ways in which HDX data can be represented and how the data
can be interpreted.
PMID- 28702520
TI - Photo-induced beta-elimination of 9-fluorenylmethanol leading to dibenzofulvene.
AB - An effective photo-induced beta-elimination of an alcohol leading to a vinyl
compound is introduced for the first time. 9-Fluorenylmethanol was irradiated in
a solution using a Xe lamp and was efficiently converted to dibenzofulvene (DBF)
(9-methylenefluorene) in the absence of base which is necessary in the
corresponding ground-state reaction.
PMID- 28702521
TI - Highly effective molecule converting strategy based on enzyme-free dual recycling
amplification for ultrasensitive electrochemical detection of ATP.
AB - An enzyme-free and highly effective molecule converting strategy based on target
driven catalytic hairpin assembly and Mg2+-dependent DNAzyme recycling dual
amplification was proposed to construct an ultrasensitive electrochemical
biosensor for adenosine triphosphate (ATP) detection.
PMID- 28702522
TI - Band alignment investigations of heterostructure NiO/TiO2 nanomaterials used as
efficient heterojunction earth-abundant metal oxide photocatalysts for hydrogen
production.
AB - Earth-abundant NiO/anatase TiO2 heteronanostructures were prepared by a
straightforward one-pot sol-gel synthetic route followed by a suitable thermal
post-treatment. The resulting 0.1-4 wt% NiO-decorated anatase TiO2 nanoparticles
were characterized by X-ray diffraction, electron microscopy, Raman and UV
visible spectroscopy and N2 sorption analysis, and showed both nanocrystallinity
and mesoporosity. The careful determination of the energy band alignment diagram
by a suitable combination of XPS/UPS and absorption spectroscopy data revealed
significant band bending at the interface of the p-n NiO/anatase TiO2
heterojunction nanoparticles. Furthermore, these heterojunction photocatalysts
exhibited an improved photocatalytic activity in H2 production by methanol
photoreforming compared to pure anatase TiO2 and commercial P25. Thus, an average
H2 production rate of 2693 MUmol h-1 g-1 was obtained for the heterojunction of a
1 wt% NiO/anatase photocatalyst, which is one of the most efficient NiO/anatase
TiO2 systems ever reported. An enhanced dissociation efficiency of the
photogenerated electron-hole pairs resulting from an internal electric field
developed at the interface of the NiO/anatase TiO2 p-n heterojunctions is
suggested to be the reason of this enhanced photocatalytic activity.
PMID- 28702524
TI - Nonadiabatic dynamics simulation of keto isocytosine: a comparison of dynamical
performance of different electronic-structure methods.
AB - The nonadiabatic dynamics of keto isocytosine in the gas phase has been
investigated using the on-the-fly trajectory surface hopping method based on two
electronic-structure methods: SA-CASSCF and ADC(2). The results estimate an
excited-state lifetime of around 1000 fs at the SA-CASSCF level, while a much
shorter lifetime of 250-350 fs is obtained at the ADC(2) level. Although three
conical intersections (CIs) (Ethyl. I, Ethyl. II and C[double bond, length as m
dash]O stretching) are relevant to the nonadiabatic decay of keto isocytosine,
their contributions to the nonadiabatic decay are highly dependent on the
electronic-structure methods employed in the dynamics simulation. The Ethyl. II
CI is the main channel in the dynamics simulations at the SA-CASSCF level, while
the C[double bond, length as m-dash]O stretching CI becomes dominant at the
ADC(2) levels. Other high-level electronic-structure methods (MR-CISD and MS
CASPT2) are involved to benchmark our dynamics results. Through the analysis of
the reaction pathways from the ground state minimum to the relevant CIs, we
expect that the excited-state dynamical features obtained at the MR-CISD and MS
CASPT2 levels should be very similar to those at the SA-CASSCF level. The
comparison of results obtained using different excited-state electronic-structure
methods could provide guidance for further studies of similar systems.
PMID- 28702525
TI - Multifunctional role of dysprosium in HfO2: stabilization of the high temperature
cubic phase, and magnetic and photoluminescence properties.
AB - Hafnium oxide (HfO2) can exist in different crystalline structures such as
monoclinic at room temperature, tetragonal at 1700 degrees C and cubic at 2600
degrees C. In the present study, nanocrystalline powders of HfO2 synthesized by a
Pechini type sol-gel technique show a monoclinic phase, P21/c, at room
temperature. By incorporating Dy into the HfO2 lattice, the intensity of all
diffraction peaks corresponding to P21/c decreases and at a concentration of 11
at% of Dy, the monoclinic phase transforms completely to the cubic phase,
Fm3[combining macron]m, showing a mixed phase of monoclinic and cubic at
intermediate concentrations (5-9 at%) of Dy. For the first time, we have
stabilized the high temperature cubic phase of HfO2 at room temperature by
incorporating Dy. Selected area electron diffraction patterns confirm the
monoclinic and the cubic phase as observed from the X-ray diffraction patterns. A
mechanism for stabilization of the high temperature cubic phase in Hf1-xDyxO2 has
been analyzed based on the substitution of dysprosium for hafnium ions and the
formation of oxygen vacancies. While ferromagnetic ordering at room temperature
observed in HfO2 nanoparticles is quenched after incorporating 1 at% of Dy,
photoluminescence (PL) studies demonstrate excellent emissions in the blue and
yellow region after exciting with UV light of wavelength 352 nm. Combining
excitation and emission profiles, we have proposed a tentative energy band
diagram illustrating the energetic processes taking place in Hf1-xDyxO2.
PMID- 28702526
TI - A comparative study of magnetization dynamics in dinuclear dysprosium complexes
featuring bridging chloride or trifluoromethanesulfonate ligands.
AB - We utilized a rigid ligand platform PyCp22- (PyCp22- = [2,6-(CH2C5H3)2C5H3N]2-)
to isolate dinuclear Dy3+ complexes [(PyCp2)Dy-(MU-O2SOCF3)]2 (1) and [(PyCp2)Dy
(MU-Cl)]2 (3) as well as the mononuclear complex (PyCp2)Dy(OSO2CF3)(thf) (2).
Compounds 1 and 2 are the first examples of organometallic Dy3+ complexes
featuring triflate binding. The isolation of compounds 1 and 3 allows us to
comparatively evaluate the effects of the bridging anions on the magnetization
dynamics of the dinuclear systems. Our investigations show that although the
exchange coupling interactions differ for 1 and 3, the dynamic magnetic
properties are dominated by relaxation via the first excited state Kramers
doublet of the individual Dy sites. Compounds 1 and 3 exhibit barriers to
magnetization reversal (Ueff = 49 cm-1) that can be favorably compared to those
of the previously reported examples of [Cp2Dy(MU-Cl)]2 (Ueff = 26 cm-1) and
[Cp2Dy(thf)(MU-Cl)]2 (Ueff = 34 cm-1).
PMID- 28702527
TI - Li-ion diffusion in Li intercalated graphite C6Li and C12Li probed by MU+SR.
AB - In order to study a diffusive behavior of Li+ in Li intercalated graphites, we
have measured muon spin relaxation (MU+SR) spectra for C6Li and C12Li synthesized
with an electrochemical reaction between Li and graphite in a Li-ion battery. For
both compounds, it was found that Li+ ions start to diffuse above 230 K and the
diffusive behavior obeys a thermal activation process. The activation energy (Ea)
for C6Li is obtained as 270(5) meV, while Ea = 170(20) meV for C12Li. Assuming a
jump diffusion of Li+ in the Li layer of C6Li and C12Li, a self-diffusion
coefficient DLi at 310 K was estimated as 7.6(3) * 10-11 (cm2 s-1) in C6Li and
14.6(4) * 10-11 (cm2 s-1) in C12Li.
PMID- 28702528
TI - Stability and growth mechanism of self-assembling putative antifreeze cyclic
peptides.
AB - Cyclic peptides (CPs) that self-assemble in nanotubes can be candidates for use
as antifreeze proteins. Based on the cyclic peptide sequence cyclo-[(l-LYS-d-ALA
l-LEU-d-ALA)2], which can stack into nanotubes, we propose a putative antifreeze
cyclic peptide (AFCP) sequence, cyclo-[(l-LYS-d-ALA)2-(l-THR-d-ALA)2], containing
THR-ALA-THR ice binding motifs. Using molecular dynamics simulations we
investigate the stability of these cyclic peptides and their growth mechanism.
Both nanotube sequences get more stable as a function of size. The relative
stability of the AFCP sequence CPNT increases at sizes greater than a dimer by
forming intermolecular THR side chain H-bonds. We find that, like the naturally
occurring AF protein from spruce budworm (Choristoneura fumiferana), the THR
distances of the AFCP's ice binding motif match the ice prism plane O-O
distances, thus making the AFCP a suitable AF candidate. In addition, we
investigated the nanotube growth process, i.e. the association/dissociation of a
single CP to an existing AFCP nanotube, by Transition Path Sampling. We found a
general dock-lock mechanism, in which a single CP first docks loosely before
locking into place. Moreover, we identified several qualitatively different
mechanisms for association, involving different metastable intermediates,
including a state in which the peptide was misfolded inside the hydrophobic core
of the tube. Finally, we find evidence for a mechanism involving non-specific
association followed by 1D diffusion. Under most conditions, this will be the
dominant pathway. The results yield insights into the mechanisms of peptide
assembly, and might lead to an improved design of self-assembling antifreeze
proteins.
PMID- 28702529
TI - Assessing chemotherapeutic effectiveness using a paper-based tumor model.
AB - In vitro models for screening new cancer chemotherapeutics often rely on two
dimensional cultures to predict therapeutic potential. Unfortunately, the
predictive power of these models is limited, as they fail to recapitulate the
complex three-dimensional environments in tumors that promote a chemoresistant
phenotype. In this study, we describe the preparation and characterization of
paper-based cultures (PBCs) engineered to assess chemotherapeutic effectiveness
in three dimensional, diffusion-limited environments. Similar environments are
found in poorly vascularized tumors. Monotonic gradients develop across these
cultures, which are assembled by stacking cell-laden paper scaffolds to yield
thick tissue-like structures, and provide distinct chemical environments for each
scaffold. After prolonged incubation, the scaffolds can simply be peeled apart
and analyzed. Through fluorescence imaging, we determined that viable and
proliferative cell populations were most abundant in scaffolds close to the
nutrient-rich medium. By adjusting the cell density, we modulated the
spatiotemporal evolution of oxygen gradients across the cultures and correlated
these environmental changes with cellular sensitivity to SN-38 exposure. From
these results, we showed that differences in the oxygen gradients produced
cellular populations with significantly different chemosensitivities. Through
this work, we highlight PBCs ability to serve as an analytical model capable of
determining chemotherapeutic effectiveness under a range of chemical
environments.
PMID- 28702530
TI - Prediction of metallic nanotube reactivity for H2O activation.
AB - The reactivity of metallic nanotubes toward the catalysis of water dissociation,
a key step in the water gas shift reaction (WGSR), was analyzed through density
functional theory (DFT) calculations. Water dissociation was studied on surfaces
of nanotubes based on copper, gold and platinum, and also on platinum doped
copper and gold nanotubes. Gold and copper nanotubes present activities that are
similar to those of their corresponding extended surfaces but, in the case of the
Pt(5,3) nanotube, a significant improvement in the activity is found when
compared with the extended surfaces. In fact, the calculations predict the water
dissociation to be spontaneous on Pt(5,3) with a low activation energy barrier.
The platinum doping of gold and copper nanotubes leads to contrasting effects,
i.e., with a slight increase of activity found on gold and a slight decrease of
activity in the case of copper. The consideration of a Bronsted-Evans-Polanyi
(BEP) relationship to estimate the activation energy barriers for the O-H bond
break leads to a satisfactory agreement between estimated and explicitly
calculated values which suggests the validity of the BEP relationship for
qualitative predictions of the activities of metal nanotubes towards the water
dissociation reaction.
PMID- 28702523
TI - Implications of peptide assemblies in amyloid diseases.
AB - Neurodegenerative disorders and type 2 diabetes are global epidemics compromising
the quality of life of millions worldwide, with profound social and economic
implications. Despite the significant differences in pathology - much of which
are poorly understood - these diseases are commonly characterized by the presence
of cross-beta amyloid fibrils as well as the loss of neuronal or pancreatic beta
cells. In this review, we document research progress on the molecular and
mesoscopic self-assembly of amyloid-beta, alpha synuclein, human islet amyloid
polypeptide and prions, the peptides and proteins associated with Alzheimer's,
Parkinson's, type 2 diabetes and prion diseases. In addition, we discuss the
toxicities of these amyloid proteins based on their self-assembly as well as
their interactions with membranes, metal ions, small molecules and engineered
nanoparticles. Through this presentation we show the remarkable similarities and
differences in the structural transitions of the amyloid proteins through primary
and secondary nucleation, the common evolution from disordered monomers to alpha
helices and then to beta-sheets when the proteins encounter the cell membrane,
and, the consensus (with a few exceptions) that off-pathway oligomers, rather
than amyloid fibrils, are the toxic species regardless of the pathogenic protein
sequence or physicochemical properties. In addition, we highlight the crucial
role of molecular self-assembly in eliciting the biological and pathological
consequences of the amyloid proteins within the context of their cellular
environments and their spreading between cells and organs. Exploiting such
structure-function-toxicity relationship may prove pivotal for the detection and
mitigation of amyloid diseases.
PMID- 28702531
TI - Thiol-reactive (co)polymer scaffolds comprising organic arsenical acrylamides.
AB - Novel, well-defined organic arsenical homopolymers (D = 1.10-1.40) have been
synthesised via RAFT polymerisation. Copolymerisation of the As-functional
monomer with dimethylacrylamide yielded non-toxic polymer scaffolds (D ~ 1.10)
that could be manipulated in response to pH and undergo sequential reduction and
substitution in the presence of thiols including cysteine and glutathione.
PMID- 28702532
TI - A supramolecular miktoarm star polymer based on porphyrin metal complexation in
water.
AB - A novel supramolecular miktoarm star polymer was successfully constructed in
water from a pyridine end-decorated polymer (Py-PmDEGA) and a metalloporphyrin
based star polymer (ZnTPP-(PEG)4) via metal-ligand coordination. The Py-PmDEGA
moiety was prepared via a combination of reversible addition-fragmentation chain
transfer polymerization (RAFT) and subsequent aminolysis and Michael addition
reactions to introduce the pyridine end-group. The ZnTPP(PEG)4 star-polymer was
synthesized by the reaction between tetrakis(p-hydroxyphenyl)porphyrin and
toluenesulfonyl-PEG, followed by insertion of a zinc ion into the porphyrin core.
The formation of a well-defined supramolecular AB4-type miktoarm star polymer was
unambiguously demonstrated via UV-Vis spectroscopic titration, isothermal
titration calorimetry (ITC) and diffusion ordered NMR spectroscopy (DOSY).
PMID- 28702537
TI - Thermodynamic and structural properties of binary calcium silicate glasses:
insights from molecular dynamics.
AB - We study calcium silicate glass of composition (CaO)X(SiO2)(1-X), where X = 40-70
mol%, by means of molecular dynamics for different cooling rates between 1011
1013 K s-1. The thermodynamic and kinetic properties of calcium silicate
materials are determined, discussed, and correlated to local structures at short
and intermediate range orders and to the potential energies of the oxygen atoms.
We show that the amount of non-bridging oxygens and the appearance of free
oxygens are related to the increase of the glass transition temperature for an
increasing CaO content. Our results are analyzed and discussed in connection with
the available experimental data.
PMID- 28702538
TI - Epitaxial growth of aligned atomically precise chevron graphene nanoribbons on
Cu(111).
AB - Atomically precise chevron graphene nanoribbons (GNRs) have been synthesized on
Cu(111) substrates by the surface-assisted coupling of 6,11-dibromo-1,2,3,4
tetraphenyltriphenylene (C42Br2H26) and thermal cyclodehydrogenation of the
resulting polymer. The GNRs form on Cu(111) epitaxially along the <112>
crystallographic directions, which was found to be in agreement with the
computational results, and at lower temperatures than on Au(111). This work
demonstrates that the substrate plays an important role in the on-surface
synthesis of GNRs and can result in new assembly modes of GNR structures.
PMID- 28702539
TI - A divergent [5+2] cascade approach to bicyclo[3.2.1]octanes: facile synthesis of
ent-kaurene and cedrene-type skeletons.
AB - A solvent-dependent oxidative dearomatization-induced divergent [5+2] cascade
approach to bicyclo[3.2.1]octanes was described. This novel protocol enables a
facile synthesis of a series of diversely functionalized ent-kaurene and cedrene
type skeletons in good yields and excellent diastereoselectivities.
PMID- 28702540
TI - Ultralow power switching in a silicon-rich SiNy/SiNx double-layer resistive
memory device.
AB - Here we demonstrate low-power resistive switching in a Ni/SiNy/SiNx/p++-Si device
by proposing a double-layered structure (SiNy/SiNx), where the two SiN layers
have different trap densities. The LRS was measured to be as low as 1 nA at a
voltage of 1 V, because the SiNx layer maintains insulating properties for the
LRS. The single-layered device suffers from uncontrollability of the conducting
path, accompanied by the inherent randomness of switching parameters, weak
immunity to breakdown during the reset process, and a high operating current. On
the other hand, for a double-layered device, the effective conducting path in
each layer, which can determine the operating current, can be well controlled by
the ICC during the initial forming and set processes. A one-step forming and
progressive reset process is observed for a low-power mode, which differs from
the high-power switching mode that shows a two-step forming and reset process.
Moreover, nonlinear behavior in the LRS, whose origin can be attributed to the P
F conduction and F-N tunneling driven by abundant traps in the silicon-rich SiNx
layer, would be beneficial for next-generation nonvolatile memory applications by
using a conventional passive SiNx layer as an active dielectric.
PMID- 28702541
TI - Enhanced polarization-sensitive terahertz emission from vertically grown graphene
by a dynamical photon drag effect.
AB - Improving terahertz (THz) emission from graphene is a challenge for graphene
based THz photonics as graphene demonstrates a weak light-matter interaction.
With a unique ultra-black surface structure, vertically grown graphene (VGG) is
proposed to enhance the light-matter interaction and further enhance THz
emission. Herein, enhanced THz radiation is observed by THz time-domain emission
spectroscopy from VGG compared with single-layer graphene. The radiated THz
amplitude shows a linear dependence on pump power, which demonstrates a second
order nonlinear effect. Considering the symmetry of VGG on a substrate, we can
exclude the optical rectification effect and photogalvanic effect (PGE) by the
D6h point group with centrosymmetry. Thus we analyze the transient photocurrent
related to THz emission only by the photon drag effect (PDE). The polarization
sensitive THz radiation signals are wave-vector reliant and demonstrate cos 2phi
and sin 2phi dependence on the polarization angles of the pump laser. This is
consistent with the theoretical analysis of PDE. Our results show the enhanced,
ultrafast, broadband THz radiation property of VGG, which paves the way for high
performance THz emitters and THz detectors based on graphene materials.
PMID- 28702542
TI - Methanol oxidation on stoichiometric and oxygen-rich RuO2(110).
AB - We used temperature-programmed reaction spectroscopy (TPRS) to investigate the
adsorption and oxidation of methanol on stoichiometric and O-rich RuO2(110)
surfaces. We find that the complete oxidation of CH3OH is strongly preferred on
stoichiometric RuO2(110) during TPRS for initial CH3OH coverages below ~0.33 ML
(monolayer), and that partial oxidation to mainly CH2O becomes increasingly
favored with increasing CH3OH coverage from 0.33 to 1.0 ML. We present evidence
that an adsorbed CH2O2 species serves as the key intermediate to complete
oxidation and that CH2O2 formation is intrinsically facile but becomes limited by
the availability of bridging O-atoms on stoichiometric RuO2(110) at initial CH3OH
coverages above 0.33 ML. We show that methanol molecules adsorbed in excess of
0.33 ML dehydrogenate to mainly CH2O and desorb during TPRS, with adsorbed CH3O
groups mediating the evolution of both CH2O and CH3OH. We find that O-rich
RuO2(110) surfaces are also highly active toward methanol oxidation and that
selectivity toward the complete oxidation of methanol increases markedly with
increasing coverage of on-top O-atoms (Oot) on RuO2(110). Our results demonstrate
that CH3OH species adsorbed within Oot-rich domains react efficiently during
TPRS, in parallel with reaction of CH3OH adsorbed initially on cus-Ru sites. The
data suggests that the facile hydrogenation of Oot atoms and the resulting
desorption of H2O at low-temperature (<~400 K) provides an efficient pathway for
restoring reactive O-atoms and thereby promoting complete oxidation of methanol
on the O-rich RuO2(110) surface.
PMID- 28702544
TI - Pyrite form of group-14 element pernitrides synthesized at high pressure and high
temperature.
AB - The chemical reaction of group-14 elements with molecular nitrogen at pressures
above 60 GPa successfully leads to the formation of pyrite-type pernitrides.
These new crystalline group-14 elemental pernitrides were found to show a bulk
modulus higher than the other known group-14 elemental nitrides. Our results
offer significant new progress in the solid-state chemistry of nitrides.
PMID- 28702543
TI - Accelerated molecular dynamics simulation analysis of MSI-594 in a lipid bilayer.
AB - Multidrug resistance against the existing antibiotics is one of the most
challenging threats across the globe. Antimicrobial peptides (AMPs), in this
regard, are considered to be one of the effective alternatives that can overcome
bacterial resistance. MSI-594, a 24-residue linear alpha-helical cationic AMP,
has been shown to function via the carpet mechanism to disrupt bacterial membrane
systems. To better understand the role of lipid composition in the function of
MSI-594, in the present study, eight different model membrane systems have been
studied using accelerated molecular dynamics (aMD) simulations. The simulated
results are helpful in discriminating the particular effects of cationic MSI-594
against zwitterionic POPC, anionic POPG and POPS, and neutral POPE lipid
moieties. Additionally, the effects of various heterogeneous POPC/POPG (7 : 3),
POPC/POPS (7 : 3), and POPG/POPE (1 : 3 and 3 : 1) bilayer systems on the dynamic
interaction of MSI-594 have also been investigated. The effect on the lipid
bilayer due to the interaction with the peptide is characterized by lipid acyl
chain order, membrane thickness, and acyl-chain dynamics. Our simulation results
show that the lipid composition affects the membrane interaction of MSI-594,
suggesting that membrane selectivity is crucial to its mechanism of action. The
results reported in this study are helpful to obtain accurate atomistic-level
information governing MSI-594 and its membrane disruptive antimicrobial mechanism
of action, and to design next generation potent antimicrobial peptides.
PMID- 28702545
TI - Direct examination of the relevance for folding, binding and electron transfer of
a conserved protein folding intermediate.
AB - Near the minimum free energy basin of proteins where the native ensemble resides,
partly unfolded conformations of slightly higher energy can be significantly
populated under native conditions. It has been speculated that they play roles in
molecular recognition and catalysis, but they might represent contemporary
features of the evolutionary process without functional relevance. Obtaining
conclusive evidence on these alternatives is difficult because it requires
comparing the performance of a given protein when populating and when not
populating one such intermediate, in otherwise identical conditions. Wild type
apoflavodoxin populates under native conditions a partly unfolded conformation
(10% of molecules) whose unstructured region includes the binding sites for the
FMN cofactor and for redox partner proteins. We recently engineered a
thermostable variant where the intermediate is no longer detectable. Using the
wild type and variant, we assess the relevance of the intermediate comparing
folding kinetics, cofactor binding kinetics, cofactor affinity, X-ray structure,
intrinsic dynamics, redox potential of the apoflavodoxin-cofactor complex (Fld),
its affinity for partner protein FNR, and electron transfer rate within the
Fld/FNR physiological complex. Our data strongly suggest the intermediate state,
conserved in long-chain apoflavodoxins, is not required for the correct assembly
of flavodoxin nor does it contribute to shape its electron transfer properties.
This analysis can be applied to evaluate other native basin intermediates.
PMID- 28702546
TI - Two-dimensional NiO nanosheets with enhanced room temperature NO2 sensing
performance via Al doping.
AB - High-performance gas sensors based on metal oxides operated at room temperature
are of great interest due to their energy saving and cost effective
characteristics. How to improve the sensitivity of metal oxide gas sensors and
enable their room-temperature operation are challenging for their realistic
applications. In this work, we have designed and fabricated Al-doped NiO
nanosheets for greatly enhanced NO2 detection at room temperature. Different
amounts of Al were doped into two-dimensional (2D) NiO nanosheets via a fast and
facile microwave assisted solvent-thermal technique. Sensing tests of the as
fabricated devices indicated that Al doping could significantly affect the gas
sensing properties of the NiO nanosheets due to increased oxygen vacancies as
well as the formation of Lewis acid and base sites. When 12 at% of Al was added
to the raw materials, the response value of the device to 10 ppm NO2 was enhanced
more than 35 times compared with those of pure NiO nanosheets. In addition, when
the amount of Al reached 20 at%, it took only 200 s for the gas sensor to achieve
full recovery, which was a breakthrough for room temperature gas sensors based on
metal oxides. Above all, the excellent performances of the as-fabricated devices
make Al-doped NiO nanosheets a potential candidate for NO2 sensing applications.
This design strategy can also give guidance for designing high-performance gas
sensors based on other similar 2D sensing materials.
PMID- 28702547
TI - Anomalous low strain induced by surface charge in nanoporous gold with low
relative density.
AB - The surface stress induced axial strain in a fiber-like solid is larger than its
radical strain, and is also greater than the radical strain in similar-sized
spherical solids. It is thus envisaged that the surface-induced macroscopic
dimension change (i.e., actuation strain) in nanoporous gold (NPG) increases with
decreasing relative density, or alternatively, with an increasing ratio between
volumes of fiber-like ligaments and sphere-like nodes. In this study,
electrochemical actuations of NPG with similar structure sizes, same (oxide
covered) surface state but different relative densities were characterized in
situ in response to surface charging/discharging. We found that the actuation
strain amplitude did not increase, but decreased dramatically with decreasing
relative density of NPG, in contrast to the above prediction. The actuation
strain decreased abruptly when the relative density of NPG was decreased to below
0.25, when the Au content in the AuAg precursor was below 20 at%. Further studies
indicate that this anomalous behavior cannot be explained by potential- or size
dependences of the elasticity, the structure difference arising from different
dealloying rates, or additional strain induced by the external load during
dilatometry experiments. In NPG with low relative density, mutual movements of
nano-ligaments may occur in the pore space and disconnected regions, which may
compensate the local strain in ligaments and account for the anomalous low
actuation strain in macroscopic NPG samples.
PMID- 28702548
TI - Counterintuitive trends of the wetting behavior of ionic liquid-based
electrolytes on modified lithium electrodes.
AB - The demand for high energy densities has brought rechargeable lithium metal
batteries back into the research focus. Ionic liquids (ILs) are considered as
suitable electrolyte components for these systems. In this work, the wetting
behavior of 1-ethyl-3-methylimidazolium bis((trifluoromethyl)sulfonyl)imide
([C2MIm]TFSI), 1-butyl-3-methylimidazolium bis-((trifluoromethyl)sulfonyl)imide
([C4MIm]TFSI), 1-hexyl-3-methylimidazolium bis((trifluoromethyl)sulfonyl)imide
([C6MIm]TFSI), and N-butyl-N-methylpyrrolidinium
bis((trifluoromethyl)sulfonyl)imide (Pyr14TFSI) on mechanically modified lithium
electrodes, with and without lithium bis((trifluoromethyl)sulfonyl)imide (LiTFSI)
conducting salt, is investigated and is compared to an organic carbonate-based
electrolyte. Three different patterns were chosen for the lithium modification,
enabling a surface area increase of 12%, 20%, and 56% for the modified lithium
electrodes. Especially for pure ILs, the contact angle on lithium was
significantly larger with higher surface areas of the lithium electrodes. Since
the addition of LiTFSI remarkably decreased the contact angles of the ILs on the
modified lithium surfaces, it could be shown that the effect of LiTFSI can be
attributed to a decreased surface tension. This observation could be explained by
an interruption of the ordering of ionic liquid cations and anions, which is
supported by Raman spectroscopy and molecular dynamics (MD) simulations.
PMID- 28702549
TI - Functionalization of any substrate using covalently modified large area CVD
graphene.
AB - We report a novel route for the functionalization of any substrates, including
chemically inert substrates. CVD grown graphene is electrochemically
functionalized with p-(N-maleimido)phenyl residues and consecutively transferred
to various substrates. The transfer process is shown to be without noticeable
loss. The functional layer exhibits a thickness of appx. 4.5 nm.
PMID- 28702550
TI - Dissolution DNP using trityl radicals at 7 T field.
AB - Dissolution DNP has become an important method to generate highly polarized
substrates such as pyruvic acid for in vivo imaging and localized spectroscopy.
In a quest to further increase the polarization levels, which is important for in
vivo MRI employing 13C detection, we describe the design and implementation of a
new DNP polarizer that is suitable for dissolution operation at 7 T static
magnetic field and a temperature of 1.4 K. We describe all important sample
preparation steps and experimental details necessary to optimize trityl based
samples for use in our polarizer at this higher field. In [1-13C]-pyruvic acid
polarization levels of about 56% are achieved, compared to typical polarization
levels of about 35-45% at a standard field of 3.4 T. At the same time, the
polarization build-up time increases significantly from about 670 s at 3.4 T to
around 1300-1900 s at 7 T, depending on the trityl derivate used. We also
investigate the effect of adding trace amounts of Gd3+ to the samples. While one
trityl compound does not exhibit any benefit, the other profits significantly,
boosting achievable polarization by 6%.
PMID- 28702551
TI - Using a chitosan nanolayer as an efficient pH buffer to protect pH-sensitive
supramolecular assemblies.
AB - It is attractive to control the properties of macro objects and films by
employing simple nanolayer composites, as in the case of nanoarchitectured Layer
by-Layer (LbL) coating. In this paper, we use chitosan as a surface-based pH
buffer to protect adsorbed supramolecular fibres from pH-mediated disassembly.
Protons are generated on a titania surface under illumination at 405 nm leading
to an appreciable pH change on the surface. We find that supramolecular polymers
that are highly sensitive to pH change will not disassemble after irradiation if
a nanolayer of chitosan is present. We propose that chitosan can be used as an
efficient pH-responsive protective layer for pH sensitive soft materials.
PMID- 28702552
TI - Correction: A new AIE multi-block polyurethane copolymer material for subcellular
microfilament imaging in living cells.
AB - Correction for 'A new AIE multi-block polyurethane copolymer material for
subcellular microfilament imaging in living cells' by Yu-qing Niu et al., Chem.
Commun., 2017, DOI: .
PMID- 28702553
TI - Electrochemical synthesis of phthalides via anodic activation of aromatic
carboxylic acids.
AB - A novel electrochemical synthesis of phthalides was successfully developed using
anodically generated aroyloxy radicals in combination with aliphatic carboxylic
acid as cheap and readily available alkylating agent precursors.
PMID- 28702554
TI - In vitro and in vivo trackable titanocene-based complexes using optical imaging
or SPECT.
AB - A novel Ti/111In-heterometallic radiotheranostic along with non-radioactive
Ti/In, Ti/Lu, and Ti/Y analogues has been reported, thanks to the design of a
challenging synthesis of the first titanocene-DOTA ligand. The corresponding
titanocene-BODIPY complex was developed for in vitro tracking by optical imaging.
The different complexes were characterized and their antiproliferative properties
were evaluated on three cancer cell lines (A2780, B16F1, and PC3). As a proof of
concept, initial studies in healthy mice were performed with a Ti/111In
derivative to obtain information about its uptake, its biodistribution, and its
excretion. Confocal microscopy experiments were performed with fluorescent
complexes to track it in vitro.
PMID- 28702555
TI - Molecular conductors from bis(ethylenedithio)tetrathiafulvalene with
tris(oxalato)rhodate.
AB - This article reports a family of new radical-cation salts of
bis(ethylenedithio)tetrathiafulvalene (BEDT-TTF) with tris(oxalato)rhodate: three
salts with the formula beta''-(BEDT-TTF)4[(cation)Rh(C2O4)3].solvent (solvent =
fluorobenzene, chlorobenzene, or bromobenzene) and one with the formula pseudo
kappa-(BEDT-TTF)4[(NH4)Rh(C2O4)3].benzonitrile. We report here the syntheses,
crystal structures, electrical properties and Raman spectroscopy of these new
molecular conductors. The bromobenzene salt shows a decrease in resistivity below
2.5 K indicative of a superconducting transition and a Shubnikov-de Haas
oscillation with a frequency of 232 T and effective mass m* of 1.27me.
PMID- 28702556
TI - A three-state model for the photo-Fries rearrangement.
AB - A three-state model for the photo-Fries rearrangement (PFR) is proposed based on
multiconfigurational calculations. It provides a comprehensive mechanistic
picture of all steps of the reaction, from the photoabsorption to the final
tautomerization. The three states participating in the PFR are an aromatic
1pipi*, which absorbs the radiation; a pre-dissociative 1npi*, which transfers
the energy to the dissociative region; and a 1pisigma*, along which dissociation
occurs. The transfer from 1pipi* to 1npi* involves pyramidalization of the
carbonyl carbon, while transfer from 1npi* to 1pisigma* takes place through CO
stretching. Different products are available after a conical intersection with
the ground state. Among them is a recombined radical intermediate, which can
yield ortho-PFR products after an intramolecular 1,3-H tunneling. The three-state
model is developed for phenyl acetate, the basic prototype for the PFR, and it
reconciles the theory with a series of observations from time-resolved
spectroscopy. It also delivers a rational way to optimize PFR yields, since, as
shown for four different systems, diverse substituents can change the energetic
order of the 1pipi* and 1npi* states, preventing or enhancing the PFR.
PMID- 28702557
TI - Synthesis, characterization and in vitro and in vivo photodynamic activities of a
gallium(iii) tris(ethoxycarbonyl)corrole.
AB - Corroles have been previously demonstrated to be a new and promising
photosensitizer (PS) in photodynamic therapy (PDT) for cancer cells. This
research reported the preparation of an electron-deficient flat gallium(iii)
tris(ethoxycarbonyl)corrole (1-Ga). Its in vitro PDT activities towards different
cancer cell lines were examined, and the best PDT activity was observed in A549
cell lines. 1-Ga could penetrate the cell membrane rapidly and exhibit remarkable
photo-cytotoxicity. 1-Ga can induce A549 cell apoptosis via ROS-mediated
mitochondrial pathways, in which p38 and sirt-1 proteins play a key role. A PTD
test in vivo showed that 1-Ga can significantly reduce the growth of A549
xenografted tumor cells without an obvious loss of mice weight upon PDT
treatment.
PMID- 28702558
TI - High performance transparent in-plane silicon nanowire Fin-TFTs via a robust nano
droplet-scanning crystallization dynamics.
AB - High mobility, scalable and even transparent thin-film transistors (TFTs) are
always being pursued in the field of large area electronics. While excimer laser
beam-scanning can crystallize amorphous Si (a-Si) into high mobility poly-Si, it
is limited to small areas. We here demonstrate a robust nano-droplet-scanning
strategy that converts an a-Si:H thin film directly into periodic poly-Si nano
channels, with the aid of well-coordinated indium droplets. This enables the
robust batch-fabrication of high performance Fin-TFTs with a high hole mobility
of >100 cm2 V-1 s-1 and an excellent subthreshold swing of only 163 mV dec-1, via
a low temperature <350 degrees C thin film process. More importantly, precise
integration of tiny poly-Si channels, measuring only 60 nm in diameter and 2 MUm
apart on glass substrates, provides an unprecedented transparent Si-based TFT
technology to visible light, which is widely sought for the next generation of
high aperture displays and fully transparent electronics. The successful
implementation of such a reliable nano-droplet-scanning strategy, rooted in the
strength of nanoscale growth dynamics, will enable eventually the batch
manufacturing and upgrade of high performance large area electronics in general,
and high definition and scalable flat-panel displays in particular.
PMID- 28702559
TI - Synthesis, spectroscopic, electrochemical and computational studies of rhenium(i)
tricarbonyl complexes based on bidentate-coordinated 2,6-di(thiazol-2-yl)pyridine
derivatives.
AB - Nine rhenium(i) complexes possessing three carbonyl groups together with a
bidentate coordinated 2,6-di(thiazol-2-yl)pyridine derivative were synthesized to
examine the impact of structure modification of the triimine ligand on the
photophysical, thermal and electrochemical properties of [ReCl(CO)3(4-Rn-dtpy
kappa2N)]. The Re(i) complexes were fully characterized using IR, 1H and 13C,
HRMS-ESI and single crystal X-ray analysis. Their thermal properties were
evaluated using DSC and TGA measurements. Photoluminescence spectra of
[ReCl(CO)3(4-Rn-dtpy-kappa2N)] were investigated in solution and in the solid
state, at 298 and 77 K. Both emission wavelengths and quantum yields of
[ReCl(CO)3(4-Rn-dtpy-kappa2N)] were found to be structure-related, demonstrating
a crucial role of the substituent attached to the 2,6-di(thiazol-2-yl)pyridine
skeleton. In order to fully understand the photophysical properties of
[ReCl(CO)3(4-Rn-dtpy-kappa2N)], density functional theory (DFT) and time
dependent DFT (TD-DFT) calculations were performed. Furthermore, the complexes
which showed appropriate solubility in chloroform were tested as an emissive
active layer in OLED devices.
PMID- 28702560
TI - Amperometric micro pH measurements in oxygenated saliva.
AB - An amperometric micro pH sensor has been developed based on the chemical
oxidation of carbon fibre surfaces (diameter of 9 MUm and length of ca. 1 mm) to
enhance the population of surface quinone groups for the measurement of salivary
pH. The pH analysis utilises the electrochemically reversible two-electron, two
proton behaviour of surface quinone groups on the micro-wire electrodes. A
Nernstian response is observed across the pH range 2-8 which is the pH range of
many biological fluids. We highlight the measurement of pH in small volumes of
biological fluids without the need for oxygen removal and specifically the micro
pH electrode is examined by measuring the pH of commercial synthetic saliva and
authentic human saliva samples. The results correspond well with those obtained
by using commercial glass pH electrodes on large volume samples.
PMID- 28702561
TI - Vibronic coupling in organic semiconductors for photovoltaics.
AB - Light-induced charge transfer from the photoexcited donor to the acceptor is the
fundamental step towards current generation in organic solar cells. Experimental
evidence for efficient charge separation on ultrafast time scales has been
available for quite some time. Yet even today, the elementary mechanisms
underlying this process in organic semiconductors and in particular the role of
the coherent wave-like motion of electrons and nuclei for the charge separation
are still a matter of considerable debate. In this perspective, we present a
survey of the current understanding on the role of quantum coherences in organic
semiconductors. Specifically, we discuss the role of vibronic couplings for
ultrafast charge separation dynamics with particular attention on the potential
implications for the light-to-current conversion process in photovoltaic devices.
PMID- 28702562
TI - Influence of transition metal doping on the electronic and optical properties of
ReS2 and ReSe2 monolayers.
AB - We investigate the structural, electronic and optical properties of transition
metal doped triclinic monolayered rhenium disulfide and diselenide (ReS2 and
ReSe2) by means of quantum mechanical calculations. The calculated electronic
band gaps for ReS2 and ReSe2 monolayers are 1.43 eV and 1.23 eV, respectively,
with both having a non-magnetic ground state. The calculated dopant
substitutional energies under both Re-rich and X(S or Se)-rich conditions show
that it is possible to experimentally synthesize transition metal doped ReX2
(where X is S or Se) monolayer systems. We found that the presence of dopant ions
(such as V, Cr, Mn, Fe Co, Nb, Mo, Ta and W) in the ReS2 and ReSe2 monolayers
significantly modifies their electronic ground states with consequent
introduction of defect levels and modification of the density of states profile.
However, it was found that Mn doped structures show a very minute reduction of
the electronic band gap. We found that a ferro- or a non-magnetic ground state
configuration was obtained depending on the choice of dopant ions in ReS2 and
ReSe2 monolayers. Cr, Fe and Co doping result in a ferro-magnetic ground state
configuration of the ReX2 structures. The calculated absorption and reflectivity
spectra show that this class of dopants causes a general increase in the
absorption spectral peaks but only a minute influence on the reflectivity.
Optical anisotropy was observed depending on whether the direction of
polarization in the xy-plane is either parallel or perpendicular.
PMID- 28702563
TI - Remarkable differences in the biochemical fate of Cd2+, Hg2+, CH3Hg+ and
thimerosal in red blood cell lysate.
AB - Humans are environmentally exposed to potentially toxic Cd and Hg species and to
the Hg compound thimerosal (THI), an antibactericidal vaccine additive. Previous
studies have revealed that Cd2+, Hg2+ and CH3Hg+ are taken up by red blood cells
(RBCs) and bind to cytosolic glutathione (GSH) and/or hemoglobin (Hb). Since
interactions in the cytosol of RBCs may be linked to their hemolysis, a more
comprehensive characterization of these interactions was sought. After the
addition of each Cd and Hg species to RBC lysate, the mixtures were analyzed
after 5 min, 2 h and 6 h by size-exclusion chromatography (SEC) coupled on-line
to an inductively coupled plasma atomic emission spectrometer (ICP-AES). In
contrast to previous studies, however, reducing conditions were maintained by
employing a 100 mM Tris buffer mobile phase (pH 7.4), which contained ~2.5 mM of
glutathione (GSH). At >=2 h, ~85% of Cd2+ weakly interacted with hemoglobin (Hb),
while ~13% eluted as (GS)xCd and ~2% bound to a >=70 kDa Cd-binding protein. In
contrast, ~6% of Hg2+ co-eluted with Hb at all time points, while ~94% eluted as
(GS)xHg. The results for CH3Hg+ showed that ~5% of Hg co-eluted with Hb, while
for THI this percentage gradually increased to 12% (6 h). The remaining Hg eluted
as GS-HgCH3 and GS-HgCH2CH3. Our results revealed remarkable differences in the
interaction of the investigated Cd and Hg species with cytosolic RBC
constituents. The formation of (Hb)xHg species, regardless of which Hg compound
was added, suggests their mammalian toxicology to be intertwined with the
metabolism of Fe.
PMID- 28702564
TI - Ru-Based CO releasing molecules with azole ligands: interaction with proteins and
the CO release mechanism disclosed by X-ray crystallography.
AB - fac-[RuII(CO)3Cl2(N3-Imidazole)] (RuIIIM), fac-[RuII(CO)3Cl2(N3-methyl
imidazole)] (RuIIMIM) and fac-[RuII(CO)3Cl2(N3-methyl-benzimidazole)] (RuIIMBI)
are three ruthenium based CO releasing molecules (Ru-CORMs) that are cytotoxic
towards ovarian and colon carcinoma cell lines. Detailed structural information
on the adducts formed upon reaction of RuIIIM and RuIIMIM with hen egg white
lysozyme and of the three Ru-CORMs with bovine pancreatic ribonuclease is
provided here by X-ray crystallography. Comparative analysis of seven crystal
structures of these adducts allows one to delineate some general trends in the
reactivity of these Ru-CORMs with proteins. Indeed, in all cases Ru-CORMs bind
these model systems upon detachment of the azole ligand and concomitant
coordination to a protein His or Asp residue. Apparently the three Ru-CORMs
progressively dissociate losing azoles, chlorides, and one or two CO molecules.
Data were compared with those reported in the literature for adducts of the same
proteins with other Ru-CORMs and with in-solution data previously obtained on the
same systems. These results are potentially useful for a better understanding of
the chemistry, potential toxicity and mechanism of actions of these interesting
Ru-CORMs and are helpful in defining the molecular mechanisms of CO release.
PMID- 28702565
TI - Identifying the common genetic networks of ADR (adverse drug reaction) clusters
and developing an ADR classification model.
AB - Adverse drug reactions (ADRs) are one of the major concerns threatening public
health and have resulted in failures in drug development. Thus, predicting ADRs
and discovering the mechanisms underlying ADRs have become important tasks in
pharmacovigilance. Identification of potential ADRs by computational approaches
in the early stages would be advantageous in drug development. Here we propose a
computational method that elucidates the action mechanisms of ADRs and predicts
potential ADRs by utilizing ADR genes, drug features, and protein-protein
interaction (PPI) networks. If some ADRs share similar features, there is a high
possibility that they may appear together in a drug and share analogous
mechanisms. Proceeding from this assumption, we clustered ADRs according to
interactions of ADR genes in the PPI networks and the frequency of co-occurrence
of ADRs in drugs. ADR clusters were verified based on a side effect database and
literature data regarding whether ADRs have relevance to other ADRs in the same
cluster. Gene networks shared by ADRs in each cluster were constructed by
cumulating the shortest paths between drug target genes and ADR genes in the PPI
network. We developed a classification model to predict potential ADRs using
these gene networks shared by ADRs and calculated cross-validation AUC (area
under the curve) values for each ADR cluster. In addition, in order to
demonstrate correlations between gene networks shared by ADRs and ADRs in a
cluster, we applied the Wilcoxon rank sum statistical test to the literature data
and results of a Google query search. We attained statistically meaningful p
values (<0.05) for every ADR cluster. The results suggest that our approach
provides insights into discovering the action mechanisms of ADRs and is a novel
attempt to predict ADRs in a biological aspect.
PMID- 28702566
TI - A titanium-based metal-organic framework as an ultralong cycle-life anode for
PIBs.
AB - We achieved excellent anode performance for PIBs based on a metal-organic
framework MIL-125(Ti) for the first time. It can deliver a capacity of 208 mA h g
1 at a rate of 10 mA g-1 and a high capacity retention of 90.2% after 2000 cycles
at a high rate of 200 mA g-1 with a high coulombic efficiency. The K+ storage
mechanism is investigated by the ex situ XRD and IR techniques and confirms that
potassium ions are reversibly inserted into the organic moiety without direct
engagement of Ti ions.
PMID- 28702567
TI - Controlled self-assemblies of polystyrene-block-polydimethylsiloxane micelles in
cylindrical confinement through a micelle solution wetting method and Rayleigh
instability-driven transformation.
AB - Block copolymer micelles have been extensively discussed for many decades because
of their applications, such as lithography and drug delivery. However,
controlling the morphologies of nanostructure assembly using block copolymer
micelles as building elements remains a great challenge. In this work, we
developed a novel route to induce micelle assembly in confined geometries.
Polystyrene-block-polydimethylsiloxane (PS-b-PDMS) micelle solutions were used to
prepare micelle nanostructures, and the critical parameters affecting the
morphologies were determined. Micelle nanorods, micelle nanospheres, and multi
component nanopeapods were prepared by wetting anodic aluminum oxide (AAO)
templates with micelle solutions. Rayleigh-instability-driven transformation was
discovered to play an important role in controlling the morphologies of the
micelle nanostructures. This study not only proposes a versatile approach to
preparing block copolymer micelle nanostructures, but it also provides deeper
insight into the controlling factors of block copolymer micelle morphologies in
cylindrical confinement.
PMID- 28702568
TI - A redox-responsive selenium-containing pillar[5]arene-based macrocyclic
amphiphile: synthesis, controllable self-assembly in water, and application in
controlled release.
AB - The first selenium-containing pillar[5]arene-based macrocyclic amphiphile was
synthesized. This amphiphile self-assembled in water to form vesicles with redox
responsiveness. Furthermore, these pillar[5]arene-based vesicles were used in the
controlled release of small molecules with DOX as the model compound.
PMID- 28702569
TI - The borazine dimer: the case of a dihydrogen bond competing with a classical
hydrogen bond.
AB - Dimers of borazine were studied using matrix isolation infrared spectroscopy and
ab initio quantum chemical calculations. Computations were performed at the MP2
and M06-2X levels of theory using the 6-311++G(d,p) and aug-cc-pVDZ basis sets
for the various homodimers. At both levels of theory, an aligned stacked
structure was found to be the global minimum, which was nearly isoenergetic to a
parallel displaced structure. A T-shaped structure, where the N-H of one borazine
pointed towards the N of the second borazine, was found to be a local minimum. In
addition to these structures, a dihydrogen bonded structure, where the hydrogen
attached to the nitrogen of borazine interacted with the hydrogen attached to the
boron atom of another borazine, was also indicated. Experimentally, we observed
the T-shaped dimer and the dihydrogen bonded dimer. This is one of the rare
examples of experimental evidence for a dihydrogen bond, in a system other than
in a metal hydride. These results for the borazine dimer were clearly different
from the benzene dimer where the parallel displaced structure was found to be the
global minimum followed by the T-shaped structure at the MP2/aug-cc-pVDZ level of
theory. AIM, EDA and NBO analyses were carried out for all the structures to
explore the nature of interactions.
PMID- 28702570
TI - A hierarchical CoFeS2/reduced graphene oxide composite for highly efficient
counter electrodes in dye-sensitized solar cells.
AB - Transition metal sulfides are a kind of potential candidates for efficient and
stable CE materials in DSSCs due to their good electrocatalytic ability and
stability towards I3- reduction. However, the low conductivity of sulfides is
harmful for the electron collection and transfer process, and the
absorption/desorption and diffusion process of I-/I3- should be optimized to
achieve high electrocatalytic activity over Pt. Herein, a hierarchical
CoFeS2/reduced graphene oxide (CoFeS2/rGO) composite was rationally designed and
prepared via the in situ conversion of CoFe layer double hydroxide anchored on
rGO. Due to the synergistic effects of Co and Fe, unique 3D hierarchical
structures formed by nanosheets, and the conductivity of rGO, the CoFeS2/rGO CEs
exhibited good electrocatalytic activity and stability towards the reduction of
I3- to I-, and the DSSCs could also achieve a high efficiency of 8.82%, higher
than those of the devices based on Pt (8.40%) and pure CoFeS2 (8.30%) CEs.
Moreover, the devices also showed the characteristics of fast activity onset,
good stability, and high multiple start/stop capability. The results indicated
that the developed CoFeS2/rGO composite could be a promising alternative for Pt
in DSSCs.
PMID- 28702571
TI - Chemical functionalization and characterization of graphene-based materials.
AB - Graphene-based materials (GBMs), with graphene, their most known member, at the
head, constitute a large family of materials which has aroused the interest of
scientists working in different research fields such as chemistry, physics, or
materials science, to mention a few, arguably as no other material before. In
this review, we offer a general overview on the most relevant synthetic
approaches for the covalent and non-covalent functionalization and
characterization of GBMs. Moreover, some representative examples of the
incorporation into GBMs of electroactive units such as porphyrins,
phthalocyanines, or ferrocene, among others, affording electron donor-acceptor (D
A) hybrids are presented. For the latter systems, the photophysical
characterization of their ground- and excited-state features has also been
included, paying particular attention to elucidate the fundamental dynamics of
the energy transfer and charge separation processes of these hybrids. For some of
the presented architectures, their application in solar energy conversion schemes
and energy production has been also discussed.
PMID- 28702572
TI - Recent structural insights into the function of copper nitrite reductases.
AB - Copper nitrite reductases (CuNiR) carry out the first committed step of the
denitrification pathway of the global nitrogen cycle, the reduction of nitrite
(NO2-) to nitric oxide (NO). As such, they are of major agronomic and
environmental importance. CuNiRs occur primarily in denitrifying soil bacteria
which carry out the overall reduction of nitrate to dinitrogen. In this article,
we review the insights gained into copper nitrite reductase (CuNiR) function from
three dimensional structures. We particularly focus on developments over the last
decade, including insights from serial femtosecond crystallography using X-ray
free electron lasers (XFELs) and from the recently discovered 3-domain CuNiRs.
PMID- 28702573
TI - Liter-scale production of uniform gas bubbles via parallelization of flow
focusing generators.
AB - Microscale gas bubbles have demonstrated enormous utility as versatile templates
for the synthesis of functional materials in medicine, ultra-lightweight
materials and acoustic metamaterials. In many of these applications, high
uniformity of the size of the gas bubbles is critical to achieve the desired
properties and functionality. While microfluidics have been used with success to
create gas bubbles that have a uniformity not achievable using conventional
methods, the inherently low volumetric flow rate of microfluidics has limited its
use in most applications. Parallelization of liquid droplet generators, in which
many droplet generators are incorporated onto a single chip, has shown great
promise for the large scale production of monodisperse liquid emulsion droplets.
However, the scale-up of monodisperse gas bubbles using such an approach has
remained a challenge because of possible coupling between parallel bubbles
generators and feedback effects from the downstream channels. In this report, we
systematically investigate the effect of factors such as viscosity of the
continuous phase, capillary number, and gas pressure as well as the channel
uniformity on the size distribution of gas bubbles in a parallelized microfluidic
device. We show that, by optimizing the flow conditions, a device with 400
parallel flow focusing generators on a footprint of 5 * 5 cm2 can be used to
generate gas bubbles with a coefficient of variation of less than 5% at a
production rate of approximately 1 L h-1. Our results suggest that the
optimization of flow conditions using a device with a small number (e.g., 8) of
parallel FFGs can facilitate large-scale bubble production.
PMID- 28702574
TI - Electrogenerated chemiluminescence logic gate operations based on molecule
responsive organic microwires.
AB - Complex logic gate operations using organic microwires as signal transducers
based on electrogenerated chemiluminescence (ECL) intensity as the optical
readout signal have been developed by taking advantage of the unique ECL reaction
between organic semiconductor 9,10-bis(phenylethynyl)anthracene (BPEA) microwires
and small molecules. The BPEA microwires, prepared on cleaned-ITO substrate using
a simple physical vapor transport (PVT) method, were subsequently used for
construction of the ECL sensors. The developed sensor exhibits high ECL
efficiency and excellent stability in the presence of co-reactant tripropylamine.
Based on the remarkable detection performance of BPEA MWs/TPrA system, the
sensors manifested high sensitive ECL response in a wide linear range with low
detection limit for the detection of dopamine, proline or methylene blue, which
behaves on the basis of molecule-responsive ECL properties based on different ECL
reaction mechanisms. Inspired by this, these sensing systems can be utilized to
design OR, XOR and INHIBIT logic gates, which would be used for the determination
of dopamine, proline and ethylene blue via logic outputs. Importantly, the
individual logic gates can be easily brought together through three-input
operations to function as integrated logic gates.
PMID- 28702575
TI - Multi-walled boron nitride nanotubes as self-excited launchers.
AB - A self-excited launcher consisting of multi-walled boron nitride nanotubes
(BNNTs) has been investigated using molecular dynamics simulation. The results
show that, after a period of high frequency oscillation, the innermost BNNT can
be spontaneously ejected along its central axis at a relatively fast speed. The
launching is caused by the energy transfer between the nanotubes and without
absorbing energy from the external environment. Most self-excited launchers could
launch their innermost nanotube, although an inappropriate structure of the
nanotubes contributes to a blocked or failed launch. In addition, a launch angle
corrector and a nanotube receiver associated with a self-excited launcher are
also manufactured to precisely control the launch angle and distance of the
BNNTs. This study provides the possibility to fabricate and design self-excited
launchers using multi-walled nanotubes.
PMID- 28702576
TI - Nuclear inelastic scattering and density functional theory studies of a one
dimensional spin crossover [Fe(1,2,4-triazole)2(1,2,4-triazolato)](BF4) molecular
chain.
AB - Nuclear inelastic scattering (NIS) experiments have been performed in order to
study the vibrational dynamics of the low- and high-spin states of the
polynuclear 1D spin crossover compound [Fe(1,2,4-triazole)2(1,2,4
triazolato)](BF4) (1). Density functional theory (DFT) calculations using the
functional B3LYP* and the basis set CEP-31G for heptameric and nonameric models
of the compound yielded the normal vibrations and electronic energies for high
spin and low-spin isomers of three models differing in the distribution of
anionic trz- ligands and BF4- anions. On the basis of the obtained energies a
structural model with a centrosymmetric Fe(trzH)4(trz-)2 coordination core of the
mononuclear unit of the chain is proposed. The obtained distribution of the BF4-
counteranions in the proposed structure is similar to that obtained on the basis
of X-ray powder diffraction studies by Grossjean et al. (Eur. J. Inorg. Chem.,
2013, 796). The NIS data of the system diluted to 10% Fe(ii) content in a 90%
Zn(ii) matrix (compound (2)) show a characteristic change of the spectral pattern
of the low-spin centres, compared to the low-spin phase of the parent Fe(ii)
complex (1). DFT calculations reveal that this is caused by a change of the
structure of the neighbours of the low-spin centres. The spectral pattern of the
high-spin centres in (2) is within a good approximation identical to that of the
high-spin Fe(ii) isomer of (1). The inspection of the molecular orbitals of the
monomeric model systems of [Fe(trzH)4(trz-)2] and [Fe(trzH)6], together with
calculations of spin transition energies, point towards the importance of an
electrostatic effect caused by the negatively charged ligands. This results in
the stabilisation of the low-spin state of the complex containing the anionic
ligand and shortening of the Fe-N(trz-) compared to the Fe-N(trzH) bond in high
spin, but not in low-spin [Fe(trzH)4(trz-)2].
PMID- 28702577
TI - High magnetoresistance at low magnetic fields in self-assembled ZnO-Co
nanocomposite films.
AB - The solid phase growth of self-assembled nanocrystals embedded in a crystalline
host matrix opens up wide perspectives for the coupling of different physical
properties, such as magnetic and semiconducting. In this work, we report the
pulsed laser growth at room temperature of thin films composed of a dispersed
array of ferromagnetic Co (0001) nanoclusters with an in-plane mono-size width of
1.3 nm, embedded in a ZnO (0001) crystalline matrix. The as-grown films lead to
very high values of magnetoresistance, ranging at 9 T from -11% at 300 K to -19%
at 50 K, with a steep decrease of the magnetoresistance at low magnetic fields.
We establish the relationship between the magnetoresistance behavior and the
magnetic response of the Co nanocluster assembly. A spin-dependent tunneling of
the electrons between the Co nanoclusters through and by the semi-insulating ZnO
host is achieved in our films, promising with regard to magnetic field sensors or
Si-integrated spintronic devices. The effects of thermal annealing are also
discussed.
PMID- 28702578
TI - Reaction-diffusion with stochastic decay rates.
AB - Understanding anomalous transport and reaction kinetics due to microscopic
physical and chemical disorder is a long-standing goal in many fields including
geophysics, biology, and engineering. We consider reaction-diffusion
characterized by fluctuations in both transport times and decay rates. We
introduce and analyze a model framework that explicitly connects microscopic
fluctuations with the mescoscopic description. For broad distributions of
transport and reaction time scales we compute the particle density and derive the
equations governing its evolution, finding power-law decay of the survival
probability, and spatially varying decay that leads to subdiffusion and an
asymptotically stationary surviving-particle density. These anomalies are clearly
attributable to non-Markovian effects that couple transport and chemical
properties in both reaction and diffusion terms.
PMID- 28702579
TI - Metal-organic framework derived carbon-confined Ni2P nanocrystals supported on
graphene for an efficient oxygen evolution reaction.
AB - Metal-organic framework derived carbon-confined Ni2P nanocrystals supported on
graphene with high effective surface area, more exposed active sites, and
enhanced charge transport were successfully designed. The resulting material
shows excellent oxygen evolution reaction performance with a remarkably low
overpotential of 285 mV at 10 mA cm-2 and outstanding durability.
PMID- 28702580
TI - pLoc-mPlant: predict subcellular localization of multi-location plant proteins by
incorporating the optimal GO information into general PseAAC.
AB - One of the fundamental goals in cellular biochemistry is to identify the
functions of proteins in the context of compartments that organize them in the
cellular environment. To realize this, it is indispensable to develop an
automated method for fast and accurate identification of the subcellular
locations of uncharacterized proteins. The current study is focused on plant
protein subcellular location prediction based on the sequence information alone.
Although considerable efforts have been made in this regard, the problem is far
from being solved yet. Most of the existing methods can be used to deal with
single-location proteins only. Actually, proteins with multi-locations may have
some special biological functions. This kind of multiplex protein is particularly
important for both basic research and drug design. Using the multi-label theory,
we present a new predictor called "pLoc-mPlant" by extracting the optimal GO
(Gene Ontology) information into the Chou's general PseAAC (Pseudo Amino Acid
Composition). Rigorous cross-validation on the same stringent benchmark dataset
indicated that the proposed pLoc-mPlant predictor is remarkably superior to iLoc
Plant, the state-of-the-art method for predicting plant protein subcellular
localization. To maximize the convenience of most experimental scientists, a user
friendly web-server for the new predictor has been established at , by which
users can easily get their desired results without the need to go through the
complicated mathematics involved.
PMID- 28702581
TI - Synthesis of a Cu-infiltrated Zr-doped SBA-15 catalyst for CO2 hydrogenation into
methanol and dimethyl ether.
AB - A catalytically active nanoassembly comprising Cu-nanoparticles grown on
integrated and active supports (large pore Zr-doped mesoporous SBA-15 silica) has
been synthesized and used to promote CO2 hydrogenation. The doped mesoporous
material was synthesized using a sol-gel method, in which the pore size was tuned
between 11 and 15 nm while maintaining a specific surface area of about 700 m2 g
1. The subsequent Cu nanoparticle growth was achieved by an infiltration process
involving attachment of different functional groups on the external and internal
surfaces of the mesoporous structure such that 7-10 nm sized Cu nanoparticles
grew preferentially inside the pores. Chemisorption showed improved absorption of
both CO2 and H2 for the assembly compared to pure SBA-15 and 15% of the total CO2
was converted to methanol and dimethyl ether at 250 degrees C and 33 bar.
PMID- 28702582
TI - Recognition of phosphopeptides by a dinuclear copper(ii) macrocyclic complex in a
water : methanol 50 : 50 v/v solution.
AB - A new triethylbenzene-derived tetraazamacrocycle containing pyridyl spacers, L,
was prepared and its dinuclear copper(ii) complex was used as a receptor for the
recognition of phosphorylated peptides in aqueous solution. A detailed study of
the acid-base behaviour of L and its copper(ii) complexation properties as well
as of the cascade species with phosphorylated anions including two peptidic
substrates was carried out in a H2O/MeOH (50 : 50 v/v) solution using different
techniques, such as potentiometry, X-band EPR and DFT calculations. The
association constants of the dinuclear receptor with the phosphorylated peptides
and other anionic species revealed a clear preference towards phenylic
phosphorylated substrates, with values ranging 3.96-5.35 log units. Single
crystal X-ray diffraction determination of the dicopper(ii) complex of L showed
the copper centres at a distance of 5.812(1) A from one another, with the
phosphate group of the PhPO42- substrate well accommodated between them. X-band
EPR studies indicated a similar structure for this cascade complex and for the
other cascade complexes with the phosphorylated anions studied. DFT studies of
the [Cu2L(MU-OH)]3+ complex revealed a different conformation of the ligand that
brings the two copper centres at a very short distance of 3.94 A aided by the
presence of a bridging hydroxide anion that provides a CuOCu angle of 167.3
degrees . This complex is EPR silent, in line with the singlet ground state
obtained using CASSCF(2,2) calculations and DFT calculations with the broken
symmetry approach. This species coexists in solution with a complex in a
different conformation, and having a CuCu distance of 6.63 A, in lower
percentage.
PMID- 28702583
TI - Electrochemical and structural investigation of the interactions between
naphthalene diimides and metal cations.
AB - The effects of Li+ and Mg2+ on the electrochemical behaviour and photoreduction
of N,N'-bis(2,6-diisopropylphenyl)naphthalene diimide (Dipp2NDI) have been
investigated using cyclic voltammetry and UV-vis spectroscopy. Strong cation
anion interactions between Li+ or Mg2+ and [Dipp2NDI]2- result in solvent
dependent anodic shifts of the NDI-/2- redox couple. In organic solvents of
moderate dielectric constant and donor ability, the two, one-electron redox
processes typically observed for Dipp2NDI merge into a single, two-electron
process. This strong metal cation effect has been leveraged for the
photoreduction of Dipp2NDI to [Dipp2NDI]2-via a disproportionation process.
Chemical reduction of Dipp2NDI with iPrMgCl has allowed the isolation of Mg2+
complexes of [Dipp2NDI]2-. Single crystal X-ray diffraction was used to determine
the structure of a dimeric complex, [(Dipp2NDI)Mg2(THF)3]2, that features strong
coordination of Mg2+ by the oxygen atoms of the reduced NDI.
PMID- 28702584
TI - Cell type-selective imaging and profiling of newly synthesized proteomes by using
puromycin analogues.
AB - We have developed a versatile antibody-assisted strategy for the imaging and
profiling of newly synthesized proteomes in a cell-specific manner. This strategy
remained highly selective even in heterogeneous co-cultured cells, thus enabling
labeling and enrichment of nascent proteomes from targeted cells without the need
for physical separation.
PMID- 28702585
TI - Graphene oxide-stabilized perfluorocarbon emulsions for controlled oxygen
delivery.
AB - Perfluorocarbon (PFC) emulsions are capable of absorbing large quantities of
oxygen. They are widely used as blood alternates for quick oxygenation of
tissues. However, they are unsuitable for applications where sustained oxygen
supply is desired over an extended period of time. Here, we have designed a new
PFC oxygen delivery system that combines perfluorodecalin with graphene oxide
(GO), where GO acts both as an emulsifier and a stabilizing agent. The resulting
emulsions (PFC@GO) release oxygen at least one order of magnitude slower than
emulsions prepared with other common surfactants. The release rate can be
controlled by varying the thickness of the GO layer. Controlled release of oxygen
make these emulsions excellent oxygen carriers for applications where sustained
oxygen delivery is required e.g. in tissue regeneration and vascular wound
healing.
PMID- 28702586
TI - Selective synthesis of nitrogen bi-heteroarenes by a hydrogen transfer-mediated
direct alpha,beta-coupling reaction.
AB - By an external hydrogen transfer-mediated activation mode, we herein demonstrate
a new palladium-catalyzed direct alpha,beta-coupling of different types of N
heteroarenes. Such a selective coupling reaction proceeds with the advantages of
operational simplicity, high atom-economical efficiency, and use of safe and
abundant i-propanol as the activating agent, offering a practical way to access
nitrogen bi-heteroarenes. Preliminary exploration has revealed that the obtained
bis-1,10-phenanthroline 2qq' as a ligand is capable of improving a copper
catalyst for C-C bond formation. The work reported in this paper has built an
important basis for the creation of extended pi-conjugated systems that are of
high significance in biological, medicinal, materials and synthetic organic
chemistry as well as catalysis.
PMID- 28702587
TI - Simple fluorescence sensing of extreme acidity based on inner filter effect of
ascorbic acid to fluorescent Au nanoclusters.
AB - As acidic pH plays essential roles in several organelles, development of pH
sensors for extreme acidity is of vital importance. Herein, on the basis of the
inner filter effect (IFE) between ascorbic acid (AA) and Au nano-clusters
(AuNCs), a simple extreme acidity fluorescence sensor was developed without
complex organic synthesis. The as-prepared probe can be used to detect acidity
within the pH range of 2.4-4.6. Moreover, the probe possesses high selectivity,
good photostability, and excellent reversibility for monitoring extreme acidity
in bacterial cells without the influence of autofluorescence.
PMID- 28702588
TI - l-Lysine based lipidated biphenyls as agents with anti-biofilm and anti
inflammatory properties that also inhibit intracellular bacteria.
AB - l-Lysines were conjugated to lipidated biphenyls using simple synthetic chemistry
to obtain selective membrane-active antibacterial agents that inhibit cell-wall
biosynthesis. The most selective compound bore promising activity against biofilm
related infections and intracellular bacteria, and also suppressed the
stimulation of TNF-alpha induced by lipoteichoic acid. Belligerent to resistance
development, it was active in a murine model of MRSA infection.
PMID- 28702589
TI - Lantern-shaped 3d-4f high-nuclearity clusters with magnetocaloric effect.
AB - Two lantern-shaped, high-nuclearity 3d-4f clusters {Ln52Ni52}(Ln = Gd and Dy)
were synthesized by using iminodiacetic acid (H2IDA) and isonicotinic acid (HIN)
as the co-ligand under solvothermal conditions. Magnetic studies show a large
magnetocaloric effect (MCE) for the gadolinium analogue.
PMID- 28702590
TI - Two-layer and composite films based on oxidized and fluorinated graphene.
AB - This study is devoted to the production and investigation of dielectric films,
based on oxidized and fluorinated graphene suspensions. The properties of the
graphene oxide films may be greatly improved by adding fluorographene. FG films
have transmission in the visible and near infrared ranges equal to 96-98%. Two
layer films of fluorinated graphene on graphene oxide and composite films
(composite suspension of fluorinated and oxidized graphene) exhibit good
insulating properties. Their leakage currents are lower than that in the graphene
oxide or fluorinated graphene by 3-5 orders of magnitude. A significant increase
in thermal stability and relatively low charge in the film and at the interface
with silicon (3 * 1010-1.4 * 1011 cm-2) are also found for these films. An
application of thin fluorographene films (a few nanometers) decorates and
eliminates structural defects in the graphene oxide films, resulting in
conductivity blocking in graphene oxide. The built-in charge density in the
composite film of 10-20% fluorographene in the graphene oxide is much less than
in the two-layer film (<1 * 1010 cm-2). The created two-layer and composite films
may be practically applied in 2D printed and flexible electronics as insulating
films (gate dielectric and interlayer insulator), as well as materials showing
the resistive effect.
PMID- 28702591
TI - Investigation of the effects of phase transformations in micro and nano aluminum
powders on kinetics of oxidation using thermogravimetric analysis.
AB - Aluminum micro and nanoparticles are key ingredients in the synthesis of nano
energetic materials. Hence it is important to characterize the kinetics and the
rate controlling process of their oxidation. The literature shows that the mass
diffusion and phase transformation within the aluminum oxide shell are important.
However, the description of physical processes regarding simultaneous oxidation
and phase transformation is lacking. In this paper, the controlled
thermogravimetric (TGA) oxidation of 40-60 nm and 1 um Al powders is investigated
at constant heating rates and under isothermal conditions, respectively, upon
varying the partial pressure of oxygen. It is found that the core-shell model of
homogenous oxidation is applicable to explain the TGA results when the shell does
not undergo phase transformation, which predicts the apparent activation energy
in good agreement with the literature data. On the other hand, the simultaneous
oxidation and phase transformation is able to be addressed using the JMAK model
which reveals key parameters of the rate controlling processes. Mass diffusion is
indeed rate determining during the oxidation of Al micro and nanopowders while
the kinetics of the reaction is fast. Unlike the micron powders, the particle
size distribution has a significant effect on the shape of the oxidation curves
of the nanopowders.
PMID- 28702592
TI - Inhibition of GNNQQNY prion peptide aggregation by trehalose: a mechanistic view.
AB - Deposition of amyloid fibrils is the seminal event in the pathogenesis of
numerous neurodegenerative diseases. The formation of this amyloid assembly is
the manifestation of a cascade of structural transitions including toxic oligomer
formation in the early stages of aggregation. Thus a viable therapeutic strategy
involves the use of small molecular ligands to interfere with this assembly. In
this perspective, we have explored the kinetics of aggregate formation of the
fibril forming GNNQQNY peptide fragment from the yeast prion protein SUP35 using
multiple all atom MD simulations with explicit solvent and provided mechanistic
insights into the way trehalose, an experimentally known aggregation inhibitor,
modulates the aggregation pathway. The results suggest that the assimilation
process is impeded by different barriers at smaller and larger oligomeric sizes:
the initial one being easily surpassed at higher temperatures and peptide
concentrations. The kinetic profile demonstrates that trehalose delays the
aggregation process by increasing both these activation barriers, specifically
the latter one. It increases the sampling of small-sized aggregates that lack the
beta sheet conformation. Analysis reveals that the barrier in the growth of
larger stable oligomers causes the formation of multiple stable small oligomers
which then fuse together bimolecularly. The PCA of 26 properties was carried out
to deconvolute the events within the temporary lag phases, which suggested
dynamism in lags involving an increase in interchain contacts and burial of SASA.
The predominant growth route is monomer addition, which changes to condensation
on account of a large number of depolymerisation events in the presence of
trehalose. The favourable interaction of trehalose specifically with the
sidechain of the peptide promotes crowding of trehalose molecules in its vicinity
- the combination of both these factors imparts the observed behaviour.
Furthermore, increasing trehalose concentration leads to faster expulsion of
water molecules than interpeptide interactions. These expelled water molecules
have larger translational movement, suggesting an entropy factor to favor the
assembly process. Different conformations observed under this condition suggest
the role of water molecules in guiding the morphology of the aggregates as well.
A similar scenario exists on increasing peptide concentration.
PMID- 28702593
TI - Asymmetric synthesis of new gamma-butenolides via organocatalyzed epoxidation of
chalcones.
AB - gamma-Butenolides have been recognized as an important structural framework in a
number of natural products and medicinally important agents. In this work we
describe a new metal-free sequential strategy for the asymmetric synthesis of
substituted gamma-butenolides having epoxychalcones as the advanced intermediate.
Using the optimized reaction conditions, we were able to carry out the three-step
sequence, epoxidation, olefination and hydrolysis, with only one single
chromatographic purification of the final product, furnishing new
enantiomerically enriched gamma-butenolides in moderate overall yield and good
enantiomeric excess.
PMID- 28702594
TI - LPI-ETSLP: lncRNA-protein interaction prediction using eigenvalue transformation
based semi-supervised link prediction.
AB - RNA-protein interactions are essential for understanding many important cellular
processes. In particular, lncRNA-protein interactions play important roles in
post-transcriptional gene regulation, such as splicing, translation, signaling
and even the progression of complex diseases. However, the experimental
validation of lncRNA-protein interactions remains time-consuming and expensive,
and only a few theoretical approaches are available for predicting potential
lncRNA-protein associations. Here, we presented eigenvalue transformation-based
semi-supervised link prediction (LPI-ETSLP) to uncover the relationship between
lncRNAs and proteins. Moreover, it is semi-supervised and does not need negative
samples. Based on 5-fold cross validation, an AUC of 0.8876 and an AUPR of 0.6438
have demonstrated its reliable performance compared with three other
computational models. Furthermore, the case study demonstrated that many lncRNA
protein interactions predicted by our method can be successfully confirmed by
experiments. It is indicated that LPI-ETSLP would be a useful bioinformatics
resource for biomedical research studies.
PMID- 28702595
TI - Dissolution dynamics of a suspension droplet in a binary solution for controlled
nanoparticle assembly.
AB - Toroidal microstructures of nanocolloidal assemblies promise important
applications ranging from sensing, catalysis, drug delivery, and separation. In
this work, we will first investigate the rich dissolution dynamics of a droplet
comprising a nanoparticle suspension in a binary solution, and then show that the
dissolution dynamics can be a potential approach to assembling a wide range of
colloids with microtoroids. As the sessile droplet dissolves in the binary
solution of miscible and immiscible solvents, two simultaneous effects are
observed: if the dissolution rate is sufficiently high under large concentrations
of the cosolvent in the surrounding solution, a strong plume emanates from the
droplet pole as a consequence of a body force (i.e. the Korteweg force) driven by
the chemical potential gradient between the water in the droplet and in the
surrounding phase. Concurrently, the convection drives internal recirculation
flow dynamics, leading to the inversion of the droplet curvature such that its
initially spherical shape gradually contracts to evolve into a toroidal
structure. We further demonstrate that the dissolution of a suspension droplet is
an approach to assemble nanoparticles into toroidal microstructures. The
resultant toroidal shapes are extrinsically governed by the composition and the
geometrical confinement of the surrounding solution phase.
PMID- 28702596
TI - Characterization and cardioprotective activity of anthocyanins from Nitraria
tangutorum Bobr. by-products.
AB - The Nitraria tangutorum Bobr. fruit is an indigenous berry of the shrub belonging
to the Zygophyllaceae family which grows at an altitude of over 3000 m in the
Tibetan Plateau, and has been used as a native medicinal food for treating
weakness of the spleen, stomach syndrome, dyspepsia, neurasthenia, dizziness,
etc. for thousands of years. Nowadays, N. tangutorum industrial juice by-products
generated from health food production can be a potential low cost source of some
unique bioactive ingredients. In a prior study, we established a simultaneous
microwave/ultrasonic assisted enzymatic extraction method for extracting
antioxidant ingredients from the industrial by-products of N. tangutorum juice.
In this study, these ingredients were selectively fractionated by cation-exchange
resin chromatography to obtain an anthocyanin fraction namely NJBAE. NJBAE was
found to be composed of 16 anthocyanins derived from six anthocyanidins by HPLC
ESI-MS, and has an appreciable cardioprotective effect on doxorubicin-induced
injured H9c2 cardiomyocytes. The cardioprotective mechanism research showed that
NJBAE could directly scavenge ROS, restrict further generation of ROS, promote
the activity of key antioxidase, enhance glutathione redox cycling, then affect
the apoptotic signaling changes in a positive way, and finally mediate caspase
dependent cell death pathways. Therefore, NJBAE has great potential to be used
for preventing and treating cardiovascular disease in the food, pharmaceutical
and other emerging industries.
PMID- 28702597
TI - Surfactant-assisted synthesis of ceria-titania-rich mesoporous silica materials
and their catalytic activity towards photodegradation of organic dyes.
AB - Ceria-titania doped highly ordered hexagonal and cubic mesoporous silica
composite samples with varying amounts of Ce and Ti have been synthesized using
hexadecyltrimethylammonium bromide (CTAB) surfactant as a template under basic
conditions in the presence of ammonia. The removal of the template resulted in
the formation of mesoporous composites doped with Ce and Ti, which were
thoroughly characterized via small-angle X-ray scattering (SAXS), wide-angle X
ray diffraction (WAXRD), N2 adsorption, scanning and transmission electron
microscopy analysis with energy-dispersive spectrometry mapping (SEM-TEM-EDS),
inductively coupled plasma atomic emission spectrophotometry (ICP-AES), and
ultraviolet-visible diffuse reflectance spectrometry (UV-visible). The electronic
states of Ti and Ce species present on the surface of silica were also
investigated by X-ray photoelectron spectroscopy (XPS). The catalytic activity of
these Ti-modified ceria-silica samples for the photodecomposition of rhodamine B
under visible-light irradiation was investigated. The results revealed that a
sample with a higher Ti content, as well as equal amounts of Ce and Ti, displayed
higher catalytic activity for the photodegradation of the organic dye rhodamine
B.
PMID- 28702598
TI - Two side chains, three supramolecules: exploration of fluorenone derivatives
towards crystal engineering.
AB - Structural diversity obtained through two-dimensional molecular self-assembly
induced by the chain length effect has gained immense attention, not only because
of its significance in crystal engineering but also for its potential application
in nanoscience and nanotechnology. Three kinds of fluorenone derivative, named F
C7C7, F-C14C7, and F-C14C14, were synthesized and used for systematic exploration
of their crystalline difference. At first, scanning electron microscopy and X-ray
powder diffraction were performed to investigate their differences in morphology
and three-dimensional crystal structure. Then scanning tunneling microscopy
experiments were conducted to compare the self-assembled monolayers. Moreover,
different solvents were used to repeatedly investigate the occurrence of
structural diversity. F-C7C7 could not self-assemble into a stable monolayer on
the graphite surface under ambient conditions due to its weak molecule-substrate
interaction. F-C14C7 was observed to self-assemble into twist, plier-like,
octamer-curve, and random structures in 1-octanoic acid, 1-phenyloctane, n
tetradecane, and dichloromethane, respectively. However, when the same solvents
were used and at similar concentrations, the F-C14C14 molecules were arranged
into interval, mixed, linear, and plier-like configurations. These self-assembled
nanopatterns formed under the driving forces of dipole-dipole interactions,
hydrogen bonds, and chain-chain, molecule-substrate, and molecule-solvent van der
Waals interactions. Furthermore, from the viewpoint of thermal analysis,
differential scanning calorimetry, as well as polarized optical microscopy, was
performed to further elucidate the difference between these three compounds in
the solid and liquid crystal states. The present system is believed to provide
understanding of how the chain length effect induces different crystalline
properties, and to open up the possibility of fabricating diverse self-assembled
networks for crystal engineering.
PMID- 28702599
TI - Structural-failure resistance of metal-organic frameworks toward multiple-cycle
CO2 sorption.
AB - We present the first study on the structural-failure of MOFs induced by multiple
cycle CO2 adsorption and desorption, wherein UiO-66(Zr) demonstrates a much
better resistance than HKUST-1 in 500-cycle CO2 adsorption-desorption tests. This
conclusion is supported by the higher elastic modulus of UiO-66(Zr) (ca. 28 GPa)
and retention of elastic modulus (100%) than HKUST-1 (ca. 19 GPa, 64%) measured
via multifrequency atomic force microscopy (MAFM).
PMID- 28702600
TI - An NIR-sensitive layered supramolecular nanovehicle for combined dual-modal
imaging and synergistic therapy.
AB - A supramolecular nanovehicle, denoted as ICG-DOX/Gd-LDH, was synthesized by the
co-intercalation of indocyanine green (ICG) and doxorubicin hydrochloride (DOX)
into a gallery of Gd3+-doped-layered double hydroxide (Gd-LDH) such that to
achieve a chemo-photothermal synergistic therapeutic agent. The unique structure
of Gd-LDH can not only stabilize the photothermal agent ICG to enhance the
photothermal efficiency, but also hamper the recombination between electron and
holes, leading to the generation of more reactive oxygen species (ROS) under
irradiation in the NIR range. Together with the loading capacity of DOX, ICG
DOX/Gd-LDH exhibited excellent combinatorial effects on tumor growth inhibition
in both in vitro studies on HeLa cell line and in vivo tests over tumor-bearing
mouse models. Moreover, it showed ideal ability for long-term tracing of the
carrier distribution via either MRI or fluorescence imaging. Thus, this study
indicates that Gd-LDH is a promising platform for the construction of
multifunctional formulations, especially theranostic nano-systems for cancer
treatment.
PMID- 28702601
TI - Modeling the kinetics of cobalt Fischer-Tropsch catalyst deactivation trends
through an innovative modified Weibull distribution.
AB - Since the increase in clean energy demand is driven by environmental concerns,
energy management is an ever-lasting issue globally. Among the different
scenarios for energy manufacturing, the catalytic route through the famous
process named Fischer-Tropsch Synthesis provides beneficial consequences
including pollution reduction and economic efficiency, among others. In this
regard, catalyst stability must be taken into account as a crucial performance
parameter, especially in the expensive cobalt-catalyzed CO hydrogenation
processes. As catalyst deactivation seems to be inevitable in catalytic
processes, deactivation issues such as the extent, failure rate, or reactivation
significantly influence the exploration, development, design, and operation of
commercial processes. Accordingly, the deactivation trend of a cobalt-based
catalyst was modeled via an innovative Weibull distribution base, which presents
a significant advance over the existing macroscopic deactivation models. Being
employed to obtain informative equations, the model parameters provide valuable
information about the catalyst lifetime, which can be used as a useful predictive
tool for industrial control purposes.
PMID- 28702602
TI - Synthesis of trifluoromethylated pyrazolidines by [3 + 2] cycloaddition.
AB - A highly efficient [3 + 2] cycloaddition between trifluoromethylated N
acylhydrazones and nitroolefins in the presence of potassium hydroxide under
phase transfer catalysis is developed to afford potentially bioactive
trifluoromethylated pyrazolidines, which can be further transformed into
trifluoromethylated pyrazoles in good yields.
PMID- 28702603
TI - Monocyclic aromatic compounds BnRgn(n-2)+ of boron and rare gases.
AB - The monocyclic compounds (BRg)3+(D3h), (BRg)42+(D4h), (BRg)53+(D5h) and
(BRg)64+(D6h) formed between boron and rare gases Rg (He-Rn) are theoretically
predicted to be stable structures and have pi-aromaticity with a delocalized nc
2e pi-system. For heavier rare gases Ar-Rn, the B-Rg bond energy is quite high
and ranges from 15 to 96 kcal mol-1, increasing with the ring size and the atomic
number of rare gases; the B-Rg bond length is close to the sum of covalent radii
of B and Rg atoms; NBO and AIM analyses show that the B-Rg bonds for Ar-Rn have a
typical covalent character. The B-Rg bond is stabilized mainly by sigma-donation
from the valence p orbital of Rg to the vacant valence orbital of the boron ring.
We searched for a large number of isomers for the systems of Ar and found that
the titled monocyclic compounds (BAr)3+(D3h), (BAr)42+(D4h) and (BAr)53+(D5h)
should be global energy minima. For (BAr)64+ the global energy minimum is an
octahedral caged structure, but the titled monocyclic compound is the secondary
stable local energy minimum. The energy and thermodynamic stability of the ring
BnRgn(n-2)+ cations indicate that these rare gas compounds may be viable species
in experiments.
PMID- 28702604
TI - How to efficiently tune the biradicaloid nature of acenes by chemical doping with
boron and nitrogen.
AB - Acenes are fascinating polyaromatic compounds that combine impressive
semiconductor properties with an open-shell character by varying their molecular
sizes. However, the increasing chemical instabilities related to their
biradicaloid structures pose a great challenge for synthetic chemistry. Modifying
the pi-bond topology through chemical doping allows modulation of the electronic
properties of graphene-related materials. In spite of the practical importance of
these techniques, remarkably little is known about the basic question - the
extent of the radical character created or quenched thereby. In this work, we
report a high-level computational study on two acene oligomers doubly-doped with
boron and nitrogen, respectively. These calculations demonstrate precisely which
the chemical route is in order to either quench or enhance the radical character.
Moving the dopants from the terminal rings to the central ones leads to a
remarkable variation in the biradicaloid character (and thereby also in the
chemical stability). This effect is related to a pi-charge transfer involving the
dopants and the radical carbon centers at the zigzag edges. This study also
provides specific guidelines for a rational design of large polyaromatic
compounds with enhanced chemical stability.
PMID- 28702605
TI - A Schiff base platform: structures, sensing of Zn(ii) and PPi in aqueous medium
and anticancer activity.
AB - A reaction of N1,N3-bis(3-methoxysalicylidene) diethylenetriamine (H2Vd) and
Zn(NO3)2.6H2O, ZnBr2, ZnI2 and Cd(NO3)2.4H2O in a methanol solution led to zinc
and cadmium complexes of different nuclearities, [Zn2(Vd.H)2(X)2].CH3OH (X = NO3,
Br, I) [1a, 1b and 1c] and Cd3(Vd)2(NO3)2 (2). In 1(a-c), two H2Vd ligands bridge
the two metal centers whereas in 2, they provide sideways support to two terminal
Cd2+ ions, providing an all-oxygen envelope to the central Cd2+ ion. All four
compounds were characterized by elemental analysis, FT-IR spectroscopy and single
crystal X-ray diffraction analysis. Complexes 1(a-c) exhibit dinuclear
structures, whereas 2 exhibits a nearly linear trinuclear structure. The
structural differences among these complexes are attributable to various
coordination modes and flexible configurations of the H2Vd ligand. The ligand
H2Vd is an excellent probe for sensing Zn2+ in solution, whereas complexes 1(a-c)
are able to selectively detect pyrophosphate (PPi) in aqueous medium. The
structure of the pyrophosphate (PPi) complex has been proposed using DFT
calculations and the selectivity is due to the unique ability of this anion to
simultaneously coordinate to both the Zn metal centers. The anticancer activity
of complexes 1(a-c) was also explored.
PMID- 28702606
TI - Adsorption and growth of palladium clusters on graphdiyne.
AB - The density functional formalism has been used to investigate the stability and
the properties of small palladium clusters supported on graphdiyne layers. The
large triangular holes existing on the graphdiyne structure provide efficient
sites to hold the clusters at small distances from the plane of the graphdiyne
layer. The cluster adsorption energies, between 3 and 4 eV, are large enough to
maintain the clusters tightly bound to the triangular holes. The competition
between dispersion of Pd atoms on graphdiyne and growth of Pd clusters in the
triangular holes of the layer is also discussed. In addition, the triangular
holes can be simultaneously decorated with clusters on both sides. This indicates
that palladium clusters could be used to build nanostructures formed by stacked
graphdiyne layers with tailored interlayer distances controlled by the size of
the clusters. The size of the clusters also controls the electronic HOMO-LUMO gap
of the material.
PMID- 28702607
TI - Perturbation of cationic equilibrium by cucurbit-7-uril.
AB - The effect of cucurbit-7-uril (CB-7) on a cationic mixture with same charge has
been investigated by studying monocationic mixtures of 2-(4'-N,N
dimethylaminophenyl)imidazo[4,5-b]pyridine (DMAPIP-b) and 2-(4'-N,N
dimethylaminophenyl)imidazo[4,5-c]pyridine (DMAPIP-c). The pKa of both the guests
increases in CB-7. DMAPIP-b forms all three monocations in the ground and the
excited states in aqueous as well as in CB-7 solution. However, CB-7 shifts the
equilibrium more towards the less polar MC2 and MC3. On the other hand, DMAPIP-c
exists only as MC1 and MC3 in aqueous solution, however, in CB-7 it exists not
only as MC1 and MC3 but also as MC2 in CB-7 in the ground state. In the excited
state, as in aqueous solution MC1 forms MC2 by biprotonic phototautomerism in CB
7. The association constants of monocations suggest a pyridyl nitrogen position
dependence. All the MC-CB-7 complexes are optimized by density functional theory
(DFT).
PMID- 28702608
TI - Point-of-care testing: applications of 3D printing.
AB - Point-of-care testing (POCT) devices fulfil a critical need in the modern
healthcare ecosystem, enabling the decentralized delivery of imperative clinical
strategies in both developed and developing worlds. To achieve diagnostic utility
and clinical impact, POCT technologies are immensely dependent on effective
translation from academic laboratories out to real-world deployment. However, the
current research and development pipeline is highly bottlenecked owing to
multiple restraints in material, cost, and complexity of conventionally available
fabrication techniques. Recently, 3D printing technology has emerged as a
revolutionary, industry-compatible method enabling cost-effective, facile, and
rapid manufacturing of objects. This has allowed iterative design-build-test
cycles of various things, from microfluidic chips to smartphone interfaces, that
are geared towards point-of-care applications. In this review, we focus on
highlighting recent works that exploit 3D printing in developing POCT devices,
underscoring its utility in all analytical steps. Moreover, we also discuss key
advantages of adopting 3D printing in the device development pipeline and
identify promising opportunities in 3D printing technology that can benefit
global health applications.
PMID- 28702609
TI - Pd-Catalyzed regioselective C-H halogenation of quinazolinones and
benzoxazinones.
AB - A Pd-catalyzed ortho-selective halogenation of benzoxazinone and quinazolinone
scaffolds has been described employing N-halosuccinimide as both a halogen source
and an oxidant reagent via C-H bond activation. This transformation shows high
chemo- and regioselectivities and demonstrates a broad range of benzoxazinone and
quinazolinone substrates with different functional groups and has been scaled up
to the gram level.
PMID- 28702610
TI - New insights into the interstratification phenomenon in layered double hydroxides
(LDHs): a comparison of experimental and computational results for ZnAl-LDH
containing bis-tetrazole.
AB - In the present paper, successful preparation of ZnAl layered double hydroxides
(LDHs) containing bis-tetrazole anions with both typical and interstratified
arrangements is reported. The mechanism of the single-anion interstratified
arrangement remains a long-standing and overwhelming challenge in the chemistry
of LDHs. To address this issue, the arrangement of layers, the positioning of
anions in the interlayer space, and the cationic ratio of layers were studied by
the application of a series of laboratory methods including X-ray diffraction
(XRD), thermal analyses (TGA, DTG, and DTA), elemental analysis (CHN), and energy
dispersive X-ray (EDX) methods, together with computer simulations performed by
using Dmol3, Forcite, and Reflex modules. The obtained information demonstrated
the dependence of interstratification on the type, size, and charge distribution
of the intercalated anions, and the cationic ratio of the LDH layers. At the end,
a new comprehensive mechanism is proposed for single-anion interstratification in
layered double hydroxides by considering the results of this research study and
other related works.
PMID- 28702611
TI - Atomistic dynamics of sulfur-deficient high-symmetry grain boundaries in
molybdenum disulfide.
AB - As a common type of structural defect, grain boundaries (GBs) play an important
role in tailoring the physical and chemical properties of bulk crystals and their
two-dimensional (2D) counterparts such as graphene and molybdenum disulfide
(MoS2). In this study, we explore the atomic structures and dynamics of three
kinds of high-symmetry GBs (alpha, beta and gamma) in monolayer MoS2. Atomic
resolution transmission electron microscopy (TEM) is used to characterize their
formation and evolutionary dynamics, and atomistic simulation based analysis
explains the size distribution of alpha-type GBs observed under TEM and the inter
GB interaction, revealing the stabilization mechanism of GBs by pre-existing
sulfur vacancies. The results elucidate the correlation between the observed GB
dynamics and the migration of sulfur atoms across GBs via a vacancy-mediated
mechanism, offering a new perspective for GB engineering in monolayer MoS2, which
may be generalized to other transition metal dichalcogenides.
PMID- 28702612
TI - Rapid, label-free CD4 testing using a smartphone compatible device.
AB - The most recent guidelines have called for a significant shift towards viral load
testing for HIV/AIDS management in developing countries; however point-of-care
(POC) CD4 testing still remains an important component of disease staging in
multiple developing countries. Advancements in micro/nanotechnologies and
consumer electronics have paved the way for mobile healthcare technologies and
the development of POC smartphone-based diagnostic assays for disease detection
and treatment monitoring. Here, we report a simple, rapid (30 minutes) smartphone
based microfluidic chip for automated CD4 testing using a small volume (30 MUL)
of whole blood. The smartphone-based device includes an inexpensive (<$5) cell
phone accessory and a functionalized disposable microfluidic device. We evaluated
the performance of the device using spiked PBS samples and HIV-infected and
uninfected whole blood, and compared the microfluidic chip results with the
manual analysis and flow cytometry results. Through t-tests, Bland-Altman
analyses, and regression tests, we have shown a good agreement between the
smartphone-based test and the manual and FACS analysis for CD4 count. The
presented technology could have a significant impact on HIV management in
developing countries through providing a reliable and inexpensive POC CD4
testing.
PMID- 28702613
TI - Four-component zinc-porphyrin/zinc-salphen nanorotor.
AB - An off-axis supramolecular rotor was composed of four components: a zinc
porphyrin based stator with four phenanthroline stations and a zinc-salphen based
rotator were self-assembled with DABCO and four copper(i) ions to furnish the
rotor ROT-2 in quantitative yield. The DABCO serves as a connecting axle between
the rotator and the stator, while the rotator is additionally connected to two
copper(i)-loaded phenanthroline stations of the stator via its two pyridine
terminals (Npy -> [Cu(phen)]+). For the thermally activated rotation both Npy ->
[Cu(phen)]+ interactions have to be cleaved. Due to the high energy barrier of
the rotation the slow motion was monitored by ROESY. The reduced speed (k298 =
0.2 s-1) was rationalised in terms of ground state stabilisation of the rotor as
suggested by computational insight. Additional VT 1H-NMR investigation was
undertaken to study the motion of DABCO that is sandwiched between zinc porphyrin
and zinc salphen. The diagnostic splitting of the geminal DABCO protons was
rationalised on the basis of the asymmetry induced by the salphen that generates
a diastereotopic environment. Computations reproduced the experimental NMR with
excellent agreement.
PMID- 28702614
TI - On the role of resonantly stabilized radicals in polycyclic aromatic hydrocarbon
(PAH) formation: pyrene and fluoranthene formation from benzyl-indenyl addition.
AB - Resonantly stabilized radicals, such as propargyl, cyclopentadienyl, benzyl, and
indenyl, play a vital role in the formation and growth of polycyclic aromatic
hydrocarbons (PAHs) that are soot precursors in engines and flames. Pyrene is
considered to be an important PAH, as it is thought to nucleate soot particles,
but its formation pathways are not well known. This paper presents a reaction
mechanism for the formation of four-ring aromatics, pyrene and fluoranthene,
through the combination of benzyl and indenyl radicals. The intermediate species
and transition structures involved in the elementary reactions of the mechanism
were studied using density functional theory, and the reaction kinetics were
evaluated using transition state theory. The barrierless addition of benzyl and
indenyl to form the adduct, 1-benzyl-1H-indene, was found to be exothermic with a
reaction energy of 204.2 kJ mol-1. The decomposition of this adduct through H
abstraction and H2-loss was studied to determine the possible products. The rate
of-production analysis was conducted to determine the most favourable reactions
for pyrene and fluoranthene formation. The premixed laminar flames of toluene,
ethylbenzene, and benzene were simulated using a well-validated hydrocarbon fuel
mechanism with detailed PAH chemistry after adding the proposed reactions to it.
The computed and experimentally observed species profiles were compared to
determine the effect of the new reactions for pyrene and fluoranthene formation
on their concentration profiles. The role of benzyl and indenyl combination in
PAH formation and growth is highlighted.
PMID- 28702615
TI - Thiourea derivatives as chelating agents for bioconjugation of rhenium and
technetium.
AB - Potential tetradentate thiocarbamoylbenzamidine derivatives H4L have been
synthesized from the corresponding benzimidoyl chlorides and triglycine. They are
suitable chelating agents for the oxidotechnetium(v) and oxidorhenium(v) cores
and form stable, neutral [MO(HL)] complexes with an equatorial SN3 coordination
sphere and an additional, uncoordinated carboxylic group, which can be used for
bioconjugation. Representatives of the rhenium and 99Tc products have been
isolated and analyzed with spectroscopic methods and X-ray diffraction.
Bioconjugates of these complexes with angiotensin-II have been synthesized and
structurally characterized. Analogous 99mTc complexes have been produced and
tested in vitro and in vivo. The experiments confirm a considerable stability for
the [99mTc(HL)] product as well as for its bioconjugate and recommend this class
of compounds for further bioconjugation studies towards clinical applications.
PMID- 28702616
TI - Damping mechanism and theoretical model of electrorheological elastomers.
AB - As a smart soft material, electrorheological elastomers (EREs) present tunable
damping capacity and adjustable dynamic moduli on applying an electric field.
Most of the previous studies focused on their dynamic moduli, while the damping
performance has been neglected. In this study, the damping capacity of two kinds
of EREs containing bare TiO2 and silane coupling agent-modified TiO2 particles
were tested and compared as a function of strain amplitude. The results indicate
that the modified TiO2 particle filled EREs present lower damping capacity when
the strain amplitude exceeds 10%, indicating that the interfacial friction
between the modified TiO2 particles and the matrix is decreased due to the
stronger interface strength. A theoretical model is developed to describe the
damping behaviour of the EREs, which is divided into the intrinsic damping, the
interface damping and the electric field induced damping. The experimental
results are well matched with the damping curves given by this model under
various electric field strengths, and the difference between the damping capacity
of the ERE containing bare TiO2 particles and the one containing modified TiO2
particles can be mainly ascribed to the effect of weakly and strongly bonded
interface damping.
PMID- 28702617
TI - Retrograde behavior revisited: implications for confined fluid phase equilibria
in nanopores.
AB - Many fluid mixtures exhibit retrograde behavior, including those that define
natural gases. While the behavior is well understood for mixtures in bulk, it is
not so in nanosize porous space that dominates shale formations in unconventional
reservoirs. The lack of experimental data creates the need for modeling works to
make estimates as good as possible due to immediate needs in gas recovery.
However, such efforts have been straying without firm guidance from systematic
studies over what we have known so far. This article is intended to present the
results of such a study that would incite further investigations in this area of
research. Revisiting the retrograde behavior in the bulk is appropriate to start
with, followed by a short review of what we know about fluids confined in
nanosize pores. Based on this information, implications for the behavior of
confined mixtures in the retrograde region can be inferred. The implied features
that have been supported by experimental evidence are the locations of the
confined dew point and bubble point at low temperatures, which are both at
pressures lower than their bulk counterparts. Another feature found in this study
is completely new, and therefore still open for further investigation. We reveal
that the dew-point and bubble-point curves of confined mixtures end at moderate
pressures on a multiphase curve, beyond which equilibrium occurs among the bulk
and confined phases. The well-known points in the bulk retrograde region, i.e.
the critical point and cricondenbar, are consequently absent in confined
mixtures.
PMID- 28702618
TI - Copper(ii) complexes of functionalized 2,2':6',2''-terpyridines and 2,6
di(thiazol-2-yl)pyridine: structure, spectroscopy, cytotoxicity and catalytic
activity.
AB - Six new copper(ii) complexes with 2,2':6',2''-terpyridine (4'-Rn-terpy) [1 (R1 =
furan-2-yl), 2 (R2 = thiophen-2-yl), and 3 (R3 = 1-methyl-1H-pyrrol-2-yl)] and
2,6-di(thiazol-2-yl)pyridine derivatives (Rn-dtpy) [4 (R1), 5 (R2), and 6 (R3)]
have been synthesized by a reaction between copper(ii) chloride and the
corresponding ligand. The complexes have been characterized by UV-vis and IR
spectroscopy, and their structures have been determined by X-ray analysis. The
antiproliferative potential of copper(ii) complexes of 2,2':6',2''-terpyridine
and 2,6-di(thiazol-2-yl)pyridine derivatives towards human colorectal (HCT116)
and ovarian (A2780) carcinoma as well as towards lung (A549) and breast
adenocarcinoma (MCF7) cell lines was examined. Complex 1 and complex 6 were found
to have the highest antiproliferative effect on A2780 ovarian carcinoma cells,
particularly when compared with complex 2, 3 with no antiproliferative effect.
The order of cytotoxicity in this cell line is 6 > 1 > 5 > 4 > 2 ~ 3. Complex 2
seems to be much more specific towards colorectal carcinoma HCT116 and lung
adenocarcinoma A549 cells. The viability loss induced by the complexes agrees
with Hoechst 33258 staining and typical morphological apoptotic characteristics
like chromatin condensation and nuclear fragmentation. The specificity towards
different types of cell lines and the low cytotoxic activity towards healthy
cells are of particular interest and are a positive feature for further
developments. Complexes 1-6 were also tested in the oxidation of alkanes and
alcohols with hydrogen peroxide and tert-butyl-hydroperoxide (TBHP). The most
active catalyst 4 gave, after 120 min, 0.105 M of cyclohexanol + cyclohexanone
after reduction with PPh3. This concentration corresponds to a yield of 23% and
TON = 210. Oxidation of cis-1,2-dimethylcyclohexane with m-CPBA catalyzed by 4 in
the presence of HNO3 gave a product of a stereoselective reaction (trans/cis =
0.47). Oxidation of secondary alcohols afforded the target ketones in yields up
to 98% and TON = 630.
PMID- 28702619
TI - A general method for ultrathin 1D oxide nanomaterials.
AB - By utilizing the interaction between inorganic species and organic surfactants,
the ordered layered mesostructures were generated for the synthesis of the one
dimensional oxide nanomaterials. The oxide nanomaterial products which evolved
from the above layered structures were demonstrated as ultrathin (less than 2 nm)
one-dimensional structures with superior catalytic performance. The synthetic
method based on layered structures can be extended to prepare other one
dimensional oxide nanomaterials with the same ultrathin structures.
PMID- 28702620
TI - Nanoparticle delivery of curcumin induces cellular hypoxia and ROS-mediated
apoptosis via modulation of Bcl-2/Bax in human neuroblastoma.
AB - In this study, several formulations of nanoceria and dextran-nanoceria with
curcumin, each demonstrated to have anti-cancer properties, were synthesized and
applied as treatment for human childhood neuroblastoma. The anti-cancer
activities of these formulations were explored in neuroblastoma models of both
MYCN-amplified and non-amplified cell lines. Ceria nanoparticles, coated with
dextran and loaded with curcumin, were found to induce substantial cell death in
neuroblastoma cells (up to a 2-fold and a 1.6-fold decrease in cell viability for
MYCN-upregulated and normal expressing cell lines, respectively; *p < 0.05) while
producing no or only minor toxicity in healthy cells (no toxicity at 100 MUM; **p
< 0.01). This formulation evokes prolonged oxidative stress, stabilizing HIF
1alpha, and inducing caspase-dependent apoptosis (up to a 2.4-fold increase over
control; *p < 0.05). Overall, nano-therapeutic treatments showed a more
pronounced effect in MYCN-amplified cells, which are traditionally more resistant
to drug therapies. These results represent a very promising alternative to small
molecule drug therapies for robust cancers.
PMID- 28702621
TI - Identification of perturbed signaling pathways from gene expression data using
information divergence.
AB - Abnormal regulation of signaling pathways is the key causative factor in several
diseases. Although many methods have been proposed to identify significantly
differential pathways between two conditions via microarray gene expression
datasets, most of them concentrate on differences in the pathway components
either the differential expression or the correlation of genes in a given
pathway. However, as biological functional units, signaling pathways may have
diverse activity patterns across different biological contexts. In order to
detect overall changes in pathways, we propose an analysis model called SPAID
(Signaling Pathway Analysis based on Information Divergence). SPAID is based on
the concept of information divergence, which can be used to compare two
conditions by computing the differential probability distribution of the
regulation capacity. We compared SPAID with several classical algorithms using
different datasets, and the results indicate that SPAID produces higher
repeatability, has better performance and universality, and extracts more
comprehensive information regarding the underlying biological processes. In
conclusion, by introducing the idea of information divergence, our study measures
differences in pathways from an overall perspective and will provide a
complementary analysis framework for pathway analysis.
PMID- 28702622
TI - Mechanism of ion transport in perfluoropolyether electrolytes with a lithium
salt.
AB - Perfluoropolyethers (PFPEs) are polymer electrolytes with fluorinated carbon
backbones that have high flash points and have been shown to exhibit moderate
conductivities and high cation transference numbers when mixed with lithium
salts. Ion transport in four PFPE electrolytes with different endgroups was
characterized by differential scanning calorimetry (DSC), ac impedance, and
pulsed-field gradient NMR (PFG-NMR) as a function of salt concentration and
temperature. In spite of the chemical similarity of the electrolytes, salt
diffusion coefficients measured by PFG-NMR and the glass transition temperature
measured by DSC appear to be uncorrelated to ionic conductivity measured by ac
impedance. We calculate a non-dimensional parameter, beta, that depends on the
salt diffusion coefficients and ionic conductivity. We also use the Vogel-Tammann
Fulcher relationship to fit the temperature dependence of conductivity. We
present a linear relationship between the prefactor in the VTF fit and beta; both
parameters vary by four orders of magnitude in our experimental window. Our
analysis suggests that transport in electrolytes with low dielectric constants
(low beta) is dictated by ion hopping between clusters.
PMID- 28702623
TI - Oxygen storage properties of hexagonal HoMnO3+delta.
AB - Structural and oxygen content changes of hexagonal HoMnO3+delta manganite at the
stability boundary in the perovskite phase have been studied by X-ray diffraction
and thermogravimetry using in situ oxidation and reduction processes at elevated
temperatures in oxygen and air. The oxygen storage properties during structural
transformation between stoichiometric Hex0 and oxygen-loaded Hex1 phases,
transition temperatures and kinetics of the oxygen incorporation and release are
reported for materials prepared by the solid-state synthesis and high-impact
mechanical milling. Long-term annealing experiments have shown that the Hex0
(delta = 0) -> Hex1 (delta ~ 0.28) phase transition is limited by the surface
reaction and nucleation of the new phase for HoMnO3+delta 15MM. The temperatures
of Hex0 <-> Hex1 transitions have been established at 290 degrees C and 250
degrees C upon heating and cooling, respectively, at a rate of 0.1 degrees min
1, also indicating that the temperature hysteresis of the transition could
possibly be as small as 10 degrees C in the equilibrium. Ball-milling of
HoMnO3+delta has only a small effect on improving the speed of the
reduction/oxidation processes in oxygen, but importantly, allowed for
considerable oxygen incorporation in air at a temperature range of 220-255
degrees C after prolonged heating. The Mn 2p XAS results of the Mn valence in
oxygen loaded samples support the oxygen content determined by the TG method. The
magnetic susceptibility data of the effective Mn valence gave inconclusive
results due to dominating magnetism of the Ho3+ ions. Comparison of HoMnO3+delta
with previously studied DyMnO3+delta indicates that a tiny increase in the ionic
size of lanthanide has a huge effect on the redox properties of hexagonal
manganites and that practical properties could be significantly improved by
synthesizing the larger average size (Y,Ln)MnO3+delta manganites.
PMID- 28702624
TI - Investigating the magnitude and source of orientation-dependent interactions
between TiO2 crystal surfaces.
AB - The oriented attachment (OA) of nanocrystals is a widely recognized non-classical
crystallization mechanism. A fundamental understanding of the forces that governs
the dynamics of particle movement, co-alignment, and attachment is needed to
control crystal growth by OA. However, much remains unknown about the forces in
the long range and molecular detail (such as the interfacial structure) effects
in the short range, particularly in liquid suspensions. Using atomic force
microscopy-based dynamic force spectroscopy to directly measure the adhesive
force between two rutile TiO2 (001) crystal surfaces as a function of the lattice
mismatch angle in water, we show that the forces exhibit 90 degrees periodicity
with respect to the lattice mismatch angle, which is generally consistent with
the square-lattice arrangement of Ti4+ centers on the rutile TiO2 (001) surface.
van der Waals and hydrogen bonding are the origin of adhesive forces. Molecular
dynamics simulations that incorporate relevant molecular details provide a
qualitative explanation for the observed orientation-dependence and suggest that
hydrogen bonding is predicted to be the main source of the forces in a short
range.
PMID- 28702625
TI - Facile synthesis and enhanced electrochemical properties of reduced graphene
oxide/MoS2/polyaniline ternary composites.
AB - In this study, ternary composites of reduced graphene oxide/molybdenum
disulfide/polyaniline (rGEO/MoS2/PANI) were prepared via a two-stage facile
synthesis including a hydrothermal reaction and polymerization at room
temperature which makes the materials much easier for industrialization. The
doping of reduced graphene oxide (rGEO) decreases the aggregation of MoS2 and
enhances the electronic conductivities of MoS2, thus exhibiting better
capacitance properties (531 F g-1 at 1 A g-1) and cycling stabilities (86.7%
retained capacitance over 3000 cycles at 1 A g-1) of ternary composites than a
uniform material (MoS2) or binary materials (MoS2/PANI). The combined effects
between the three components make the composites obtain both pseudocapacitance
and double-layer capacitance, which can be used to explain the improvement of
electrochemical performances.
PMID- 28702626
TI - The formation mechanism of the initial C-C chain in ethanol synthesis on gamma
AlOOH(100).
AB - An in-depth understanding of the reaction mechanism at the molecular level is the
key to guide the synthesis of ethanol over the CuZnAl catalyst, which is one of
the major challenges for ethanol application in energy. Reported herein is a
density functional theory study of ethanol synthesis from mixed methanol and
syngas on the gamma-AlOOH(100) surface. The possible elementary reactions are
unambiguously identified and for the first time we confirm the high reactivity of
the gamma-AlOOH(100) surface for the initial C-C chain formation via CO insertion
into CH3, which has a 62.8 kJ mol-1 (0.65 eV) activation barrier that is
significantly lower than the barriers previously reported. And its corresponding
reaction energy is -288.2 kJ mol-1 (-2.99 eV). Bader charge analyses indicate
that it is advantageous for the nucleophilic attack of CO to the neighboring CH3
on the gamma-AlOOH(100) surface. Our calculations show that ethanol synthesis
starts with CH3OH dissociation, goes through CH3O dissociation to yield CH3,
subsequently, CO inserts into CH3 to form CH3CO, which is further hydrogenated to
yield CH3CHO and eventually obtain C2H5OH. And the formation of intermediate CH3
is the rate-determining step of the overall reaction. The results not only
provide new mechanistic insights into the role of gamma-AlOOH but also may be
useful for the rational designing and optimizing of the CuZnAl catalyst for
ethanol synthesis.
PMID- 28702627
TI - Clean air in the Anthropocene.
AB - In atmospheric chemistry, interactions between air pollution, the biosphere and
human health, often through reaction mixtures from both natural and anthropogenic
sources, are of growing interest. Massive pollution emissions in the Anthropocene
have transformed atmospheric composition to the extent that biogeochemical
cycles, air quality and climate have changed globally and partly profoundly. It
is estimated that mortality attributable to outdoor air pollution amounts to 4.33
million individuals per year, associated with 123 million years of life lost.
Worldwide, air pollution is the major environmental risk factor to human health,
and strict air quality standards have the potential to strongly reduce morbidity
and mortality. Preserving clean air should be considered a human right, and is
fundamental to many sustainable development goals of the United Nations, such as
good health, climate action, sustainable cities, clean energy, and protecting
life on land and in the water. It would be appropriate to adopt "clean air" as a
sustainable development goal.
PMID- 28702628
TI - Blend configuration in functional polymeric materials with a high lignin content.
AB - Lignins upgrade the lignocellulosic cell-wall domains in all vascular plants;
they embody 20-30% of terrestrial organic carbon. For 50 years, mistaken
assumptions about the configuration of lignin have hindered the development of
useful polymeric materials with a lignin content above 40 wt%. Now, polymeric
materials composed only of methylated softwood lignin derivatives can exhibit
better tensile behavior than polystyrene. Marked improvements may be achieved
with small quantities (5-10 wt%) of miscible blend components as simple as
poly(ethylene glycol). These observations contradict commonly held views about
crosslinking or hyper-branching in lignin chains. The hydrodynamic compactness of
the macromolecular lignin species arises from powerful noncovalent interactions
between the lignin substructures. Individual lignin components undergo
association to form macromolecular complexes that are preserved in plastics with
a very high lignin content. Material continuity results from interpenetration
between the peripheral components in adjoining lignin complexes. Through
interactions with the peripheral domains, miscible blend components modulate the
strength and ductility of these utterly original lignin-based plastics.
PMID- 28702629
TI - The synthesis of polysubstituted indoles from 3-bromo-2-indolyl phosphates.
AB - A novel methodology for the synthesis of functionalised indoles based on the
cross-coupling reactions of 3-bromo-2-indolyl phosphates is described. The
preparation involves the conversion of easily available 2-oxindoles to 3,3
dibromo-2-oxindoles followed by the Perkow reaction affording 3-bromo-2-indolyl
phosphates. Then bromine atom is substituted regioselectively by the Suzuki
coupling reaction. We observed that aluminum chloride promoted the reaction of 3
substituted-2-indolyl phosphates with organozinc reagents furnishing 2,3
disubstituted indoles as final products. The overall diversity and efficiency of
the methodology was demonstrated by the synthesis of bioactive molecule from
easily available substances.
PMID- 28702630
TI - Synthesis and incorporation of an advanced lipid peroxidation end-product
building block into collagen mimetic peptides.
AB - Advanced lipid peroxidation end-products (ALEs) accumulate with ageing and
oxidative stress-related diseases. Despite their potential therapeutic value,
there are no suitably protected ALE building blocks reported in the literature to
enable their site-specific incorporation into synthetic peptides. The synthesis
of an Fmoc-protected ALE building block, N?-(3-methylpyridinium)lysine (MP
lysine) and its incorporation into collagen model peptides is reported.
PMID- 28702631
TI - Assembly of multi-flavored two-dimensional colloidal crystals.
AB - We systematically investigate the assembly of binary multi-flavored colloidal
mixtures in two dimensions. In these mixtures all pairwise interactions between
species may be tuned independently. This introduces an additional degree of
freedom over more traditional binary mixtures with fixed mixing rules, which is
anticipated to open new avenues for directed self-assembly. At present, colloidal
self-assembly into non-trivial lattices tends to require either high pressures
for isotropically interacting particles, or the introduction of directionally
anisotropic interactions. Here we demonstrate tunable assembly into a plethora of
structures which requires neither of these conditions. We develop a minimal model
that defines a three-dimensional phase space containing one dimension for each
pairwise interaction, then employ various computational techniques to map out
regions of this phase space in which the system self-assembles into these
different morphologies. We then present a mean-field model that is capable of
reproducing these results for size-symmetric mixtures, which reveals how to
target different structures by tuning pairwise interactions, solution
stoichiometry, or both. Concerning particle size asymmetry, we find that domains
in this model's phase space, corresponding to different morphologies, tend to
undergo a continuous "rotation" whose magnitude is proportional to the size
asymmetry. Such continuity enables one to estimate the relative stability of
different lattices for arbitrary size asymmetries. Owing to its simplicity and
accuracy, we expect this model to serve as a valuable design tool for engineering
binary colloidal crystals from multi-flavored components.
PMID- 28702632
TI - Strong spin frustration and negative magnetization in LnCu3(OH)6Cl3 (Ln = Nd and
Sm) with triangular lattices: the effects of lanthanides.
AB - Herbertsmithite- and kapellasite-type compounds with triangular lattices (i.e.
Kagome) as the most promising candidates for realizing the exotic quantum spin
liquid (QSL) state have recently attracted significant attention in condensed
matter physics and materials science but are often adversely affected by
dimensional imperfections arising from significant cation mixing. Also,
interaction mechanisms between the Kagome lattices and ionic impurities remain
unclear. Herein we report on the synthesis, crystal structures and magnetic
properties of a new class of kapellasite-type compounds LnCu3(OH)6Cl3 (Ln = Nd
and Sm) with two overlapped triangular lattices. These compounds are
characterized by the triangular lattices of Cu2+ superimposed by another
triangular lattice of paramagnetic Ln3+. The magnetic properties of LnCu3(OH)6Cl3
feature strong spin frustrations as well as antisymmetrical Dzyaloshinskii-Moriya
interactions resulting in canted antiferromagnetic ordering with the Neel
temperature (TN) of ~20 K and ~18 K for NdCu3(OH)6Cl3 and SmCu3(OH)6Cl3,
respectively. Moreover, negative magnetization at low temperatures was firstly
observed in Kagome lattice compounds, arising from geometrical spin frustration
and competing interactions within two overlapped triangular lattices.
PMID- 28702633
TI - A DFT study of H-dissolution into the bulk of a crystalline Ni(111) surface: a
chemical identifier for the reaction kinetics.
AB - In this study, we investigated the diffusion of H-atoms to the subsurface and
their further diffusion into the bulk of a Ni(111) crystal by means of density
functional theory calculations in the context of thermal and plasma-assisted
catalysis. The H-atoms at the surface can originate from the dissociative
adsorption of H2 or CH4 molecules, determining the surface H-coverage. When a
threshold H-coverage is passed, corresponding to 1.00 ML for the crystalline
Ni(111) surface, the surface-bound H-atoms start to diffuse to the subsurface. A
similar threshold coverage is observed for the interstitial H-coverage. Once the
interstitial sites are filled up with a coverage above 1.00 ML of H, dissolution
of interstitial H-atoms to the layer below the interstitial sites will be
initiated. Hence, by applying a high pressure or inducing a reactive plasma and
high temperature, increasing the H-flux to the surface, a large amount of
hydrogen can diffuse in a crystalline metal like Ni and can be absorbed. The
formation of metal hydride may modify the entire reaction kinetics of the system.
Equivalently, the H-atoms in the bulk can easily go back to the surface and
release a large amount of heat. In a plasma process, H-atoms are formed in the
plasma, and therefore the energy barrier for dissociative adsorption is
dismissed, thus allowing achievement of the threshold coverage without applying a
high pressure as in a thermal process. As a result, depending on the crystal
plane and type of metal, a large number of H-atoms can be dissolved (absorbed) in
the metal catalyst, explaining the high efficiency of plasma-assisted catalytic
reactions. Here, the mechanism of H-dissolution is established as a chemical
identifier for the investigation of the reaction kinetics of a chemical process.
PMID- 28702634
TI - Controlling biomineralisation with cations.
AB - The production of polymers for controlling calcite growth is a well-known
approach in biomineralising organisms. Numerous studies have shown that polymers
significantly influenced the growth rate and morphology of CaCO3 but little is
known about how the polymers are actually controlled by the organisms. Here we
show that cations control the effect of polysaccharides and that these processes
have been in place for at least 60 million years. We studied the interaction
between cleaved samples of pure calcite and ancient coccolith associated
polysaccharides (aPS) that we had extracted from the samples of Cretaceous chalk,
in solutions that contained one of the common seawater cations, K+, Ca2+, Mg2+
and Sr2+. With atomic and chemical force microscopy (AFM and CFM), we showed that
K+, Ca2+ and Sr2+ complex aPS through a weak, outer sphere bonding, giving the
aPS affinity to sites on steps and terraces. In contrast, Mg2+ enhanced the
formation of stronger and longer aPS complexes, resulting in low affinity to
calcite terraces and strong affinity to steps. It is known that adsorption is
influenced by ionic potential and ionic strength. Our results show that cation
polysaccharide complexing can modify the effectiveness of the polymer. Thus,
creating organic molecules with cation complexing ability is an effective
strategy for regulating mineral growth, both now and in the past.
PMID- 28702635
TI - The mechanism of nanoparticle-mediated enhanced energy transfer during high
intensity focused ultrasound sonication.
AB - In this combined experimental and theoretical research, magnetic nano-particle
(mNP) mediated energy transfer due to high intensity-focused ultrasound (HIFU)
sonication has been evaluated. HIFU sonications have been performed on phantoms
containing three different volume percentages (0%, 0.0047%, and 0.047%) of mNPs
embedded in a tissue mimicking material (TMM). A theoretical model has been
developed to calculate the temperature rise in the phantoms during HIFU
sonication. It is observed from theoretical calculation that the phonon layer at
the interface of the mNPs and TMM dominates the attenuation for higher (0.047%)
concentration. However, for a lower concentration (0.0047%) of mNPs, intrinsic
absorption is the dominating mechanism. Attenuation due to the viscous drag
becomes the dominating mechanism for larger size mNPs (>1000 nm). At a higher
concentration (0.047%), it is observed from theoretical calculations that the
temperature rise is 25% less for gold nano-particles (gNPs) when compared to
mNPs. However, at lower concentrations (0.0047% and 0.002%), the difference in
temperature rise for the mNPs and gNPs is less than 2%.
PMID- 28702636
TI - Fe3O4@Au@mSiO2 as an enhancing nanoplatform for Rose Bengal photodynamic
activity.
AB - A novel nanoplatform composed of three types of materials with different
functionalities, specifically core-shell Fe3O4@Au nanoparticles encapsulated near
the outer surface of mesoporous silica (mSiO2) nanoparticles, has been
successfully synthesised and used to enhance the efficiency of a photosensitiser,
namely Rose Bengal, in singlet oxygen generation. Fe3O4 is responsible for the
unusual location of the Fe3O4@Au nanoparticle, while the plasmonic shell acts as
an optical antenna. In addition, the mesoporous silica matrix firmly encapsulates
Rose Bengal by chemical bonding inside the pores, thus guaranteeing its
photostability, and in turn making the nanosystem biocompatible. Moreover, the
silica surface of the nanoplatform ensures further functionalisation on demand.
PMID- 28702637
TI - Athermal repair of nanoscale defects in optical materials using a femtosecond
laser.
AB - Ion implantation is widely used to fabricate advanced optical and optoelectronic
materials and devices. However, nanoscale defects generated during the ion
implantation process severely affect the quality and properties of the material
and device. Here, combining computational simulations and experiments, we
investigate the mechanism for defect repair in fused silica after Cu ion
implantation using femtosecond laser irradiation with an energy fluence much
lower than the ablation threshold. Atomic force microscopy demonstrates no
unexpected ablation. The optical absorption spectra show that various types of
defects with formation energies between 1.9 and 6.2 eV can be repaired
successfully via an athermal procedure. The Raman spectra imply that the broken
chemical bonds reconnect after femtosecond laser irradiation. Our study reveals
that low-energy femtosecond laser irradiation can transfer the appropriate energy
needed to repair defects; thus it could be useful in fabricating nonlinear
optical devices due to its high spatial selectivity and convenience.
PMID- 28702638
TI - Detecting patchy nanoparticle assembly at the single-particle level.
AB - Patchy colloidal particles offer a unique platform to explore and investigate
spatially inhomogeneous colloidal interactions. In the present work we provide
direct, in situ experimental observation at the single particle level on the
colloidal interaction driven formation of a heterodimer, consisting of a patchy
nanorod and a sphere. The gold nanorods employed during the experiments feature
positively charged tip regions, while the side of the rods is covered by surface
grafted PEG. The driving force of the assembly is the electric double layer
interaction between the nanorod and the nanosphere possessing opposite surface
charge. The great advantage of using gold heterodimers is that their optical
scattering spectrum characteristics are known to be very sensitive to the actual
structure of the assembly due to plasmon hybridization. This was exploited to
determine the structure of the heterodimer in situ upon formation in aqueous
medium. The results indicate, that despite the attractive patches being located
at the nanorod tips, for the given particle pairs the spheres readily bind to the
side region of the nanorods in the aqueous medium during the assembly. Finite
element simulations of the electric double layer interaction reveal that this is
the energetically favorable configuration for the given heterodimer. This work
demonstrates the potential of in situ experiments performed at single particle
level for the characterization of self-assembling structures, which can
contribute to the development of rationally designed nanoscale building blocks.
PMID- 28702639
TI - Insights into the electron-donating and withdrawing effect of the functional
groups on mechanochemical dehydrochlorination reactions.
AB - The effect of the withdrawing ability of -CF3 groups in a large and flexible
bidentate ligand has been evaluated by monitoring the course of solid-state
dehydrochlorination reactions. We demonstrate that the coordination bond
formation does not occur by mechanochemical means from a second coordination
sphere adduct. Quantum mechanical calculations have shown that frontier molecular
orbital energy and net charges at N centers can justify the less reactive nature
of the partially fluorinated ligand, corroborating the experimental results.
PMID- 28702640
TI - A simple high-yield synthesis of high-purity Hagg carbide (chi-Fe5C2)
nanoparticles with extraordinary electrochemical properties.
AB - Iron carbides are of eminent interest in both fundamental scientific research and
in the industry owing to their properties such as excellent mechanical strength
and chemical inertness. They have been found very effective in Fischer-Tropsch
synthesis exploring heterogeneous catalysis for the production of chemicals such
as liquid fuel and they have also been employed as successful promoters for the
oxygen reduction reaction (ORR) and hydrogen evolution reaction (HER). However,
so far there have been only a few reports on the application of iron carbide
nanoparticles in the field of electrochemical sensing. Here, we present a stable
form of Hagg carbide nanoparticles synthesized from a rare form of iron(iii)
oxide (beta-Fe2O3). The as-prepared nanomaterial was characterized employing X
ray powder diffraction and Mossbauer spectroscopy to prove its composition as
well as an extraordinary high purity level. It turned out that Hagg carbide
nanoparticles prepared by thermally treated beta-Fe2O3 exhibited excellent
electrochemical properties including low charge transfer resistivity (Rct)
compared to the other tested materials. Moreover, the Hagg carbide nanoparticles
were tested as a promising electrocatalyst for voltammetric detection of the
antibiotic metronidazole proving its practical applicability.
PMID- 28702641
TI - [FeFe]-Hydrogenase H-cluster mimics mediated by naphthalene monoimide derivatives
of peri-substituted dichalcogenides.
AB - Synthetic models of the active site of [FeFe]-hydrogenase containing naphthalene
monoimide (NMI) of peri-substituted dichalcogenides as bridging linkers have been
prepared and characterized using different spectroscopic methods. The influence
of the imide functionality and the chalcogen atoms on the redox properties and
the catalytic behaviour of complexes 7-10 was studied using cyclic voltammetry.
The results revealed that the imide functionality has improved the chemical
stability of the reduced species and the replacement of the S atoms by Se caused
a cathodic shift in the oxidation peaks. Moreover, the optical properties of
compounds 1, 2, 4, and 5 and the respective diiron complexes 7-10 were
investigated by UV-Vis absorption and fluorescence spectroscopy assisted by
quantum chemical simulations. The structures of complexes 6-9 were confirmed by X
ray diffraction analysis.
PMID- 28702642
TI - Borata-Wittig olefination reactions of ketones, carboxylic esters and amides with
bis(pentafluorophenyl)borata-alkene reagents.
AB - The strongly electrophilic borane derivative amino-CH2CH2CH2-B(C6F5)26 was alpha
CH deprotonated with LiTMP to give the borata-alkene {[amino-(CH2)2-CH[double
bond, length as m-dash]B(C6F5)2-][Li+]}29 which underwent facile [2 + 2]
cycloaddition reactions with benzophenone or fluorenone to yield the respective
1,2-oxaboretanides 11a,b. Compounds 9 and 11 were characterized by the X-ray
diffraction. Thermolysis or hydrolysis of compounds 11a,b gave the corresponding
borata-Wittig olefination products 12a,b. A variety of R-CH2-CH2-B(C6F5)2 boranes
(conveniently generated by hydroboration of terminal alkenes R-CH[double bond,
length as m-dash]CH2 with Piers' borane [HB(C6F5)2]) were analogously
deprotonated to give the respective borata-alkenes 16a-e (R: Ph-CH2-, nC4H9, tBu,
Cy, PhCH2CH2-). They underwent "non-classical" borata-Wittig olefination
reactions with ethylformate to give the respective enolether carbonylation
products, or their C1-elongated aldehydes (after hydrolysis). The borata-alkene
[Ph-(CH2)2-CH[double bond, length as m-dash]B(C6F5)2-] [Li+HTMP] (16a) gave the
respective "non-classical" borata-Wittig olefination products, the enolethers
25a,b and 27, respectively, upon treatment with methyl- or ethyl acetate or gamma
butyrolactone.
PMID- 28702643
TI - Antioxidant, ACE-inhibitory and antimicrobial activity of fermented goat milk:
activity and physicochemical property relationship of the peptide components.
AB - Increasing evidence on goat milk and the health benefits of its derived products
beyond its nutritional value show its potential as a functional food. In this
study, goat milk fractions were tested for their total antioxidant capacity using
different methods (ORAC, ABTS, DPPH and FRAP), as well as their angiotensin-I
converting-enzyme inhibitory and antimicrobial (against Escherichia coli and
Micrococcus luteus) activities. Different whey fractions (whey, cation exchange
membrane permeate P and retentate R) of two fermented skimmed goat milks
(ultrafiltered goat milk fermented with the classical starter bacteria or with
the classical starter plus the Lactobacillus plantarum C4 probiotic strain) were
assessed. Additionally, P fractions were divided into two sub-fractions after
being passed through a 3 kDa cut-off membrane: (a) the permeate with peptides of
MW <3 kDa (P < 3); and (b) the retentate with peptides and proteins of MW >3 kDa
(P > 3). No differences in biological activities were observed between the two
fermented milks. However, the biological peptides present in the P < 3 fraction
showed the highest total antioxidant capacity (for the ORAC assay) and
angiotensin-I-converting-enzyme inhibitory activity. Those present in the R
fraction showed the highest total antioxidant capacity against ABTS+ and DPPH
radicals. Some antimicrobial activity against E. coli was observed for the
fermented milk containing the probiotic, which could be due to some peptides
being released by the probiotic strain. In conclusion, small and non-basic
bioactive peptides could be responsible for most of the angiotensin-I-converting
enzyme inhibitory and antioxidant activities. These findings reinforce the
potential benefits of the consumption of fermented goat milk in the prevention of
cardiovascular diseases associated with oxidative stress and hypertension.
PMID- 28702644
TI - Photoluminescent-dielectric duple switch in a perovskite-type high-temperature
phase transition compound: [(CH3)3PCH2OCH3][PbBr3].
AB - A bistable optical-electrical duple switch belongs to a class of highly
satisfying intelligent materials that can transform optical and electrical
responses simultaneously in one device. A perovskite-type high-temperature phase
transition compound with one-dimensional chain-like crystal structure,
([(CH3)3PCH2OCH3][PbBr3], 1), displays remarkable bistable photoluminescent
dielectric duple switching behaviors. The noteworthy order-disorder transition of
the phosphonium cation and the motions of anions contribute to the phase
transition, leading to the space group P21/c at a low temperature phase to C2/c
at a high temperature phase. 1 exhibits a prominent step-like dielectric anomaly
at 401.0 K and demonstrates novel optical properties with a band gap of 3.54 eV.
The photoluminescence intensity suddenly declines from 398 K to 408 K, which may
be attributed to the occurrence of phase transition. The electron cloud
distributions of the frontier orbital in compound 1 have been calculated using a
DFT program.
PMID- 28702645
TI - A Perspective - can copper complexes be developed as a novel class of
therapeutics?
AB - Although copper-ligand complexes appear to be promising as a new class of
therapeutics, other than the family of copper(ii) coordination compounds referred
to as casiopeinas these compounds have yet to reach the clinic for human use. The
pharmaceutical challenges associated with developing copper-based therapeutics
will be presented in this article along with a discussion of the potential for
high-throughput chemistry, computer-aided drug design, and nanotechnology to
address the development of this important class of drug candidates.
PMID- 28702646
TI - Low-toxicity metallosomes for biomedical applications by self-assembly of
organometallic metallosurfactants and phospholipids.
AB - A new and convenient strategy for the preparation of metallosomes has been
developed by mixing organometallic metallosurfactants and phospholipids. These
aggregates show the characteristic properties of liposomes (stability upon
dilution and low toxicity) and the toxicity is at least ten-fold lower than that
of the metallosurfactant aggregates without phospholipids.
PMID- 28702647
TI - An enhanced hTERT promoter-driven CRISPR/Cas9 system selectively inhibits the
progression of bladder cancer cells.
AB - The current therapies for treating tumors are lacking in efficacy and
specificity. Synthetic biology principles may bring some new possible methods for
curing cancer. Here we present a synthetic logic circuit based on the CRISPR/Cas9
system. The CRISPR/Cas9 technology has been applied in many biological fields,
including cancer research. In this study, the expression of Cas9 nuclease was
controlled indirectly by an enhanced hTERT promoter using the GAL4/upstream
activating sequence (UAS) binding system. Cas9 was driven by 5XUAS, single guide
RNA (sgRNA) was used to target mutant or wild-type HRAS, and the fusion gene GAL4
P65 was driven by the enhanced hTERT promoter. The system was tested in bladder
cancer cells (T24 and 5637) and the results showed that the enhanced hTERT
promoter could drive the expression of GAL4-P65 in these bladder cancer cell
lines. Then all these devices were packed into lentivirus and the results of
quantitative real-time PCR showed that the mRNA expression level of HRAS was
selectively inhibited in the T24 and 5637 cells. The results of functional
experiments suggested that the proliferation, cell migration and invasion were
selectively suppressed, and that the apoptosis rate was increased in bladder
cancer cells but not in human foreskin fibroblasts (HFF). In conclusion, we
successfully constructed an enhanced hTERT promoter-driven CRISPR/Cas9 system and
data showed that it could selectively suppress the progression of bladder cancer
cells.
PMID- 28702648
TI - Modular interior loading and exterior decoration of a virus-like particle.
AB - Virus-like particles (VLPs) derived from the bacteriophage P22 offer an
interesting and malleable platform for encapsulation and multivalent presentation
of cargo molecules. The packaging of cargo in P22 VLP is typically achieved
through genetically enabled directed in vivo encapsulation. However, this
approach does not allow control over the packing density and composition of the
encapsulated cargos. Here, we have adopted an in vitro assembly approach to gain
control over cargo packaging in P22. The packaging was controlled by closely
regulating the stoichiometric ratio of cargo-fused-scaffold protein and wild-type
scaffold protein during the in vitro assembly. In a "one-pot assembly reaction"
coat protein subunits were incubated with varied ratios of wild-type scaffold
protein and cargo-fused-scaffold protein, which resulted in the encapsulation of
both components in a co-assembled capsid. These experiments demonstrate that an
input stoichiometry can be used to achieve controlled packaging of multiple
cargos within the VLP. The porous nature of P22 allows the escape and re-entry of
wild-type scaffold protein from the assembled capsid but scaffold protein fused
to a protein-cargo cannot traverse the capsid shell due to the size of the cargo.
This has allowed us to control and alter the packing density by selectively
releasing wild-type scaffold protein from the co-assembled capsids. We have
demonstrated these concepts in the P22 system using an encapsulated streptavidin
protein and have shown its highly selective interaction with biotin or biotin
derivatives. Additionally, this system can be used to encapsulate small molecules
coupled to biotin, or display large proteins, that cannot enter the capsid and
thus remain available for the multivalent display on the exterior of the capsid
when attached to a flexible biotinylated linker. Thus, we have developed a P22
system with controlled protein cargo composition and packing density, to which
both small and large molecules can be attached at high copy number on the
interior or exterior of the capsid.
PMID- 28702649
TI - A series of intrinsically chiral gold nanocage structures.
AB - We present a series of intrinsically chiral gold nanocage structures, Au9n+6,
which are stable for n >= 2. These structures consist of an Au9n tube which is
capped with Au3 units at each end. Removing the Au3 caps, we obtain a series of
intrinsically chiral gold nanotube structures, Au9n, which are stable for n >= 4.
The intrinsic chirality of these structures results from the helicity of the gold
strands which form the tube and not because an individual Au atom is a chiral
center. The symmetry of these structures is C3 and substructures of gold hexagons
with a gold atom in the middle are particularly prominent. We focus on the
properties of Au42 (C3) and Au105 (C3) which are the two smallest gold nanocage
structures to be completely tiled by these Au7 "golden-eye" substructures. Our
main focus is on Au42 (C3) since gold clusters in the 40-50 atom regime are
currently being investigated in gas phase experiments. We show that the
intrinsically chiral Au42 cage structure is energetically comparable with
previously reported achiral cage and compact Au42 structures. Cage structures are
of particular interest because species can be encapsulated (and stabilized)
inside the cage and we provide strong evidence that Au6@Au42 (C3) is the global
minimum Au48 structure. The intrinsically chiral gold nanocage structures, which
exhibit a range of size-related properties, have potential applications in chiral
catalysis and as components in nanostructured devices.
PMID- 28702650
TI - Influence of calcium-induced droplet heteroaggregation on the physicochemical
properties of oppositely charged lactoferrin coated lutein droplets and whey
protein isolate-coated DHA droplets.
AB - The influence of calcium-induced droplet heteroaggregation on the formation and
physicochemical stability of mixed lutein and DHA emulsions was studied.
Heteroaggregation was induced by mixing oppositely charged lactoferrin (LF)
coated lutein and whey protein isolate (WPI)-coated DHA emulsions with different
CaCl2 concentrations at pH 6.0. The droplet size, zeta-potential, transmission
physical stability and microstructure behavior (CLSM and Cryo-SEM) of single
protein emulsions and mixed emulsions were measured as a function of different
CaCl2 concentrations. Lutein degradation and DHA oxidation by measurement of
lipid hydroperoxides and thiobarbituric acid reactive substances were determined
during storage. The physical stability of the mixed emulsions could be modulated
by controlling CaCl2 concentrations. Microstructure behavior indicated that a
mixed emulsion with 30 mM CaCl2 promoted more droplets to form a special three
dimensional network and microcluster structures. The chemical stability of the
mixed lutein and DHA emulsions was obviously enhanced by the addition of 30 mM
CaCl2. The decreased surface areas of the DHA and lutein droplets and the
physical barrier of the network of heteroaggregates against transition metals and
free radicals could mainly explain the improvement in chemical stability. Calcium
induced droplet aggregation may be useful for creating specific food structures
that lead to desirable physicochemical properties of multiple functional
components.
PMID- 28702651
TI - Modeling electrical double-layer effects for microfluidic impedance spectroscopy
from 100 kHz to 110 GHz.
AB - Broadband microfluidic-based impedance spectroscopy can be used to characterize
complex fluids, with applications in medical diagnostics and in chemical and
pharmacological manufacturing. Many relevant fluids are ionic; during impedance
measurements ions migrate to the electrodes, forming an electrical double-layer.
Effects from the electrical double-layer dominate over, and reduce sensitivity
to, the intrinsic impedance of the fluid below a characteristic frequency. Here
we use calibrated measurements of saline solution in microfluidic coplanar
waveguide devices at frequencies between 100 kHz and 110 GHz to directly measure
the double-layer admittance for solutions of varying ionic conductivity. We
successfully model the double-layer admittance using a combination of a Cole-Cole
response with a constant phase element contribution. Our analysis yields a double
layer relaxation time that decreases linearly with solution conductivity, and
allows for double-layer effects to be separated from the intrinsic fluid response
and quantified for a wide range of conducting fluids.
PMID- 28702652
TI - Explicit consideration of spatial hydrogen bonding direction for activity
coefficient prediction based on implicit solvation calculations.
AB - The activity coefficient of a chemical in a mixture is important in understanding
the thermodynamic properties and non-ideality of the mixture. The COSMO-SAC model
based on the result of quantum mechanical implicit solvation calculations has
been shown to provide reliable predictions of activity coefficients for mixed
fluids. However, it is found that the prediction accuracy is in general inferior
for associating fluids. Existing methods for describing the hydrogen-bonding
interaction consider the strength of the interaction based only on the polarity
of the screening charges, neglecting the fact that the formation of hydrogen
bonds requires a specific orientation between the donor and acceptor pairs. In
this work, we propose a new approach that takes into account the spatial
orientational constraints in hydrogen bonds. Based on the Valence Shell Electron
Pair Repulsion (VSEPR) theory, the molecular surfaces associated with the
formation of hydrogen bonds are limited to those in the projection of the lone
pair electrons of hydrogen bond acceptors, in addition to the polarity of the
surface screening charges. Our results show that this new directional hydrogen
bond approach, denoted as the COSMO-SAC(DHB) model, requires fewer universal
parameters and is significantly more accurate and reliable compared to previous
models for a variety of properties, including vapor-liquid equilibria (VLE),
infinite dilution activity coefficient (IDAC) and water-octanol partition
coefficient (Kow).
PMID- 28702653
TI - Strategy towards the enantioselective synthesis of schiglautone A.
AB - Herein is described a convergent enantioselective route to an advanced
intermediate in the synthesis of schiglautone A, a Schisandra triterpenoid with
an unusual architecture. The synthetic route to this intermediate displaying 6 of
the 7 stereocenters builds upon two fragments, an aldehyde elaborated from the
Wieland-Miescher ketone, and a ketone. The preparation of the latter features a
lithiation-borylation enzymatic resolution sequence, which led to the formation
of the desired product with high enantio- and diastereoselectivities. After aldol
coupling of the two fragments, the final quaternary stereocenter was installed by
cyclopropane opening. The functionalized intermediate was isolated as a single
diastereoisomer and thus offers a valuable starting point for further synthetic
exploration.
PMID- 28702654
TI - Direct and indirect measurements of enhanced phenolic bioavailability from litchi
pericarp procyanidins by Lactobacillus casei-01.
AB - Litchi pericarp procyanidins (LPP) are dietary supplements with high antioxidant
activity, but poor oral bioavailability and efficacy. Lactobacillus casei (L.
casei-01) can transform flavan-3-ols from litchi pericarp and increase their
antioxidant ability; thus, L. casei-01 with LPP was administered to rats for four
and eight weeks to study the effect of such a combination on metabolic parameters
and on phase II metabolism and detoxification pathways in the liver as an
indirect measure for phenolic bioavailability. Our data indicated that the T-AOC
of the plasma, the liver GSH-Px and GSH-ST activity, and the expression of UGT
and SULT isoforms in the liver of the rats were all enhanced after the eight-week
administration compared with those of the control. However, at 1 h after
administration the concentration of (-)-epicatechin in the combined system was
lower than that obtained after the ingestion of LPP alone, suggesting that L.
casei-01 enhances the bioavailability of phenolics from LPP by modulating the
transformation to other compounds but not by increasing its absorption in the
native form.
PMID- 28702655
TI - Controlling the morphology and crystallization of a thiophene-based all
conjugated diblock copolymer by solvent blending.
AB - We report the crystallization and microphase separation behavior of an all
conjugated poly(3-hexylthiophene)-b-poly[3-(6-hydroxy)hexylthiophene] (P3HT-b
P3HHT) block copolymer in mixed solvents and demonstrate how the conformations of
P3HT and P3HHT chains influence the photophysical properties of the copolymer. It
is shown that the balance among pi-pi stacking of P3HT, P3HHT and microphase
separation of the copolymer can be dynamically shifted by controlling the rod-rod
interactions of the copolymer via changing the block ratio and solvent blending.
A series of nanostructures such as well-ordered nanofibers, spheres and lamellar
structures are formed and their formation mechanisms and kinetics are discussed
in detail. The variations in P3HT-b-P3HHT conformations are concomitant with a
hybrid photophysical property depending on the competition between intrachain and
interchain excitonic coupling, resulting in the transformation between J- and H
aggregation. Overall, this work demonstrates how the P3HT-b-P3HHT conformations
crystallize and phase-separate in the solution and solid state, and the
correlation between their structures and photophysical properties, which improves
our understanding of all-conjugated rod-rod block copolymer systems.
PMID- 28702656
TI - Polarization landscape effects in soft X-ray-induced surface chemical
decomposition of lead zirco-titanate, evidenced by photoelectron
spectromicroscopy.
AB - The stability of thin films of lead zirco-titanate (PZT) under intense soft X-ray
beams is investigated by time-resolved photoelectron spectromicroscopy with a
lateral resolution below 1 micrometer. Surface dissociation is observed when
samples are irradiated with intense (5 * 1023 photons per s per m2) soft X-rays,
with promotion of reduced lead on the surface. On areas exhibiting outwards
polarization (P(+)), the reduced lead is formed at the expense of P(+)-PZT. On
areas presenting co-existing P(+) states with areas without out-of-plane
polarization (P(0)), the reduced lead is formed at the expense of the P(0)-PZT
component, while the P(+)-PZT remains constant. The main dissociation mechanism
was found to be triggered by 'hot' electrons in the conduction band, with
energies exceeding the surface dissociation energies. Dissociation occurs
basically when the electron affinity is larger than the dissociation energy of
PbO (for P(+) areas) or PbO- (for P(0) areas). Such mechanisms may be adapted for
dissociation of other molecules on surfaces of ferroelectric thin films or for
quantifying the stability of ferroelectric surfaces interacting with other
radiation, with applications in the fields of photocatalysis or photovoltaic
devices.
PMID- 28702657
TI - Dissolution of anionic surfactant mesophases.
AB - Linear and circular solvent penetration experiments are used to study the
dissolution of anionic SLE3S surfactant mesophases in water. We show that a
lamellar (Lalpha) phase in contact with water will transit through a series of
cubic, hexagonal, and micellar phase bands with sharp interfaces identified from
their optical textures. In both linear and circular geometries, the kinetics of
front propagation and eventual dissolution are well described by diffusive
penetration of water, and a simple model applies to both geometries, with a
different effective diffusion coefficient for water Df as the only fitting
parameter. Finally, we show a surprising variation of dissolution rates with
initial surfactant concentration that can be well explained by assuming that the
driving force for solvent penetration is the osmotic pressure difference between
neat water and the aqueous fraction of the mesophase that is highly concentrated
in surfactant counterions.
PMID- 28702658
TI - Overcoming multidrug resistance using folate receptor-targeted and pH-responsive
polymeric nanogels containing covalently entrapped doxorubicin.
AB - Multidrug resistance (MDR) contributes to failure of chemotherapy. We here show
that biodegradable polymeric nanogels are able to overcome MDR via folic acid
targeting. The nanogels are based on hydroxyethyl methacrylamide-oligoglycolates
derivatized poly(hydroxyethyl methacrylamide-co-N-(2-azidoethyl)methacrylamide)
(p(HEMAm-co-AzEMAm)-Gly-HEMAm), covalently loaded with the chemotherapeutic drug
doxorubicin (DOX) and subsequently decorated with a folic acid-PEG conjugate via
copper-free click chemistry. pH-Responsive drug release is achieved via the acid
labile hydrazone bond between DOX and the methacrylamide polymeric network.
Cellular uptake and cytotoxicity analyses in folate receptor-positive B16F10
melanoma versus folate receptor-negative A549 lung carcinoma cells confirmed
specific uptake of the targeted nanogels. Confocal microscopy demonstrated
efficient internalization, lysosomal trafficking, drug release and nuclear
localization of DOX. We also show that DOX resistance in 4T1 breast cancer cells
results in upregulation of the folate receptor, and that folic acid targeted
nanogels can be employed to bypass drug efflux pumps, resulting in highly
efficient killing of resistant cancer cells. In conclusion, folic acid
functionalized nanogels with pH-controlled drug release seem to hold significant
potential for treating multidrug resistant malignancies.
PMID- 28702659
TI - Phase and interface determination in computer simulations of liquid mixtures with
high partial miscibility.
AB - Partially miscible solutions can represent a challenge from the computer
simulation standpoint, especially if the mutual solubility of the components is
so large that their concentrations do not change much from one phase to another.
In this case, identifying which molecules belong to which phase becomes a
complicated task. Here, we propose a density-based clustering approach with self
tuning capabilities and apply it to the case of the mixture of an ionic liquid
with benzene. The almost linear scaling of the algorithm makes it suitable for
the analysis of long Molecular Dynamics or Monte Carlo trajectories.
PMID- 28702660
TI - Poynting and reverse Poynting effects in soft materials.
AB - In 1909, J. H. Poynting conducted a series of experiments on metal wires and
found that loaded wires lengthen when twisted. Thus to maintain a constant length
in such experiments, a compressive axial force would need to be applied at the
ends of the specimen. This is the classical (positive) Poynting effect. Another
example of such an effect arises when a soft material specimen is being axially
sheared or rotated between two platens. The necessity to apply a normal force in
order to maintain the relative distance between the platens is also often
referred to as a Poynting-type effect. Both effects are inherently nonlinear
phenomena. In recent papers, experimental data on the Poynting effect in soft
solids have been reported. The seminal paper by Janmey et al. describes shearing
experiments on hydrogels, impregnated with scleroproteins such as collagen and
fibrin. It was shown that positive and negative (reverse) Poynting effects could
occur. In this and subsequent papers by several authors, the microstructure of
reinforced biogels involving semi-flexible filaments embedded in a soft matrix
was exploited to examine the character of the normal stresses. The purpose of the
present paper is to describe and review an alternative approach using the
macroscopic phenomenological theory of hyperelasticity based on nonlinear
continuum mechanics. Our aim is to demonstrate that such a theory can be used in
a very transparent way to predict the occurrence of both positive and negative
Poynting effects in anisotropic soft fibrous materials. It will be seen that
material anisotropy plays a key role in the analysis.
PMID- 28702661
TI - Clinically approved PEGylated nanoparticles are covered by a protein corona that
boosts the uptake by cancer cells.
AB - Today, liposomes are an advanced technology of drug carriers with a dozen drugs
in clinical practice and many more in clinical trials. A bottleneck associated
with the clinical translation of liposomes has long been 'opsonization', i.e. the
adsorption of plasma proteins at the liposome surface resulting in their rapid
clearance from circulation. For decades, the most popular way to avoid
opsonization has been grafting polyethylene glycol (PEG) onto the liposome
surface. Recent studies have clarified that grafting PEG onto the liposome
surface reduces, but does not completely prevent protein binding. In this work,
we employed dynamic light scattering, zeta-potential analysis, one-dimensional
sodium dodecyl sulfate polyacrylamide gel electrophoresis (1D-SDS-PAGE), semi
quantitative densitometry and cell imaging to explore the bio-nano-interactions
between human plasma (HP) and Onivyde, a PEGylated liposomal drug that has
recently been approved by the Food and Drug Administration (FDA) for the
treatment of metastatic pancreatic ductal adenocarcinoma (PDAC). To properly
evaluate the role of PEGylation, an unPEGylated variant of Onivyde was used as a
reference. Collectively, our findings suggest that: (i) although PEGylated,
Onivyde is not "stealth" in HP; (ii) surface chemistry is more important than
PEGylation in controlling the bio-nano-interactions between Onivyde and plasma
components. Of note is that the PC was found to boost the cellular uptake of
Onivyde in the pancreas ductal adenocarcinoma cell line (PANC-1) thus suggesting
its prominent role in its indication for PDAC treatment. Relevant implications
for drug delivery and drug design are discussed.
PMID- 28702662
TI - Chiral squaramide-catalysed enantioselective Michael/cyclization cascade reaction
of 3-hydroxyoxindoles with alpha,beta-unsaturated N-acylated succinimides.
AB - A bifunctional squaramide-catalysed asymmetric Michael/cyclization cascade
reaction of 3-hydroxyoxindoles with alpha,beta-unsaturated N-acylated
succinimides is disclosed. With quinine-derived squaramide as the catalyst, a
broad range of the desired spirooxindole lactone derivatives bearing two
contiguous stereocenters were obtained in good yields (up to 89%) with high
diastereoselectivities (up to >95 : 5 dr) and excellent enantioselectivities (up
to 99% ee).
PMID- 28702663
TI - Tuning phase and aging of DNA hydrogels through molecular design.
AB - The programmable, sequence-dependent hybridization of DNA has spurred the
development of DNA hydrogels, polymer networks that swell in water and are
comprised either entirely or partially of DNA. Specific applications require
hydrogels of particular structure for optimal functionality. Here, we use self
assembling, multi-valent DNA nanostars to examine how hydrogel structure is
influenced by the non-equilibrium dynamics of its interacting components. We show
that hydrogel aging kinetics - from an arrested, solid-like percolated network to
an equilibrium, phase-separated liquid analogous to coacervates - are modulated
by DNA hybridization strength and ion-specific nanostar internal flexibility.
Together, our results demonstrate strategies to control hydrogel kinetic
phenomena, and thus the hydrogel structure, through the rational design of gel
forming elements and solvent conditions.
PMID- 28702664
TI - Fast and cost-effective cyclotron production of 61Cu using a natZn liquid target:
an opportunity for radiopharmaceutical production and R&D.
AB - Following our previous work on the production of radiometals, such as 64Cu and
68Ga, through the irradiation of liquid targets using a medical cyclotron, we
describe in this paper a technique to produce 61Cu through the irradiation of
natural zinc using a liquid target. The proposed method is very cost-effective,
as it avoids the use of expensive enriched material, and is fast, as a purified
solution of 61CuCl2 is obtained in less than 30 min after the end of beam.
Considering its moderate half-life of 3.33 h and favourable decay properties as a
positron emitter, 61Cu is a very attractive nuclide for the labelling of PET
tracers for pre-clinical and clinical use with PET as well as to support the
intense R&D programmes being carried out worldwide by taking advantage of the
rich and versatile chemistry of copper.
PMID- 28702665
TI - Structural switch from a multistranded G-quadruplex to single strands as a
consequence of point mutation in the promoter of the human GRIN1 gene.
AB - A huge number of G-rich sequences forming quadruplexes are found in the human
genome, especially in telomeric regions, UTRs, and the promoter regions of a
number of genes. One such gene is GRIN1 encoding the NR1 subunit of the N-methyl
d-aspartate receptor (NMDA). Several lines of reports have implicated that
attenuated function of NMDA results in schizophrenia, a genetic disorder
characterized by hallucinations, delusions, and psychosis. Involvement of the
GRIN1 gene in the pathogenesis of schizophrenia has been extensively analysed.
Recent reports have demonstrated that polymorphism in the promoter region of
GRIN1 at position -855 (G/C) has a possible association with schizophrenia. The
binding site for the NF-kappaB transcription factor gets altered due to this
mutation, resulting in reduced gene expression as well as NMDA activity. By
combining gel electrophoresis (PAGE), circular dichroism (CD) and CD melting
techniques, the G -> C single nucleotide polymorphism (SNP) at the G-rich
sequence (d-CTTAGCCCGAGGAG[combining low line]GGGGGTCCCAAGT; GRIN1) was
investigated. We report that the GRIN1 sequence can form an
octameric/multistranded quadruplex structure with parallel conformation in the
presence of K+ as well as Na+. CD and gel studies are in good correlation in
order to detect molecularity and strand conformation. The parallel G-quadruplex
species was hypothesized to be octameric in K+/Na+ salts. The mutated sequence (d
CTTAGCCCGAGGAC[combining low line]GGGGGTCCCAAGT; GRIN1M) remained single stranded
under physiological conditions. CD melting studies support the formation of an
interstranded G-quadruplex structure by the GRIN1 sequence. Two structural models
are propounded for a multistranded parallel G-quadruplex conformation which might
be responsible for regulating the gene expression normally underlying memory and
learning.
PMID- 28702666
TI - Geometry-driven collective ordering of bacterial vortices.
AB - Controlling the phases of matter is a challenge that spans from condensed
materials to biological systems. Here, by imposing a geometric boundary
condition, we study the controlled collective motion of Escherichia coli
bacteria. A circular microwell isolates a rectified vortex from disordered
vortices masked in the bulk. For a doublet of microwells, two vortices emerge but
their spinning directions show transition from parallel to anti-parallel. A
Vicsek-like model for confined self-propelled particles gives the point where the
two spinning patterns occur in equal probability and one geometric quantity
governs the transition as seen in experiments. This mechanism shapes rich
patterns including chiral configurations in a quadruplet of microwells, thus
revealing a design principle of active vortices.
PMID- 28702667
TI - Microengineered cultures containing human hepatic stellate cells and hepatocytes
for drug development.
AB - In non-alcoholic steatohepatitis (NASH), hepatic stellate cells (HSC)
differentiate into myofibroblast-like cells that cause fibrosis, which
predisposes patients to cirrhosis and hepatocellular carcinoma. Thus, modeling
interactions between activated HSCs and hepatocytes in vitro can aid in the
development of anti-NASH/fibrosis therapeutics and lead to a better understanding
of disease progression. Species-specific differences in drug metabolism and
disease pathways now necessitate the supplementation of animal studies with data
acquired using human liver models; however, current models do not adequately
model the negative effects of primary human activated HSCs on the phenotype of
otherwise well-differentiated primary human hepatocytes (PHHs) as in vivo.
Therefore, here we first determined the long-term effects of primary human
activated HSCs on PHH phenotype in a micropatterned co-culture (MPCC) platform
while using 3T3-J2 murine embryonic fibroblasts as the control cell type since it
has been shown previously to stabilize PHH functions for 4-6 weeks. We found that
HSCs were not able to stabilize the PHH phenotype to the same magnitude and
longevity as the fibroblasts, which subsequently inspired the development of a
micropatterned tri-culture (MPTC) platform in which (a) micropatterned PHHs were
functionally stabilized using fibroblasts, and (b) the PHH phenotype was
modulated by culturing HSCs within the fibroblast monolayer at physiologically
relevant ratios with PHHs. Transwell inserts containing HSCs were placed atop
MPCCs containing fibroblasts to confirm the effects of paracrine signaling
between PHHs and HSCs. We found that while albumin and urea secretions were
relatively similar in MPTCs and MPCCs (suggesting well-differentiated PHHs),
increasing HSC numbers within MPTCs downregulated hepatic cytochrome-P450 (2A6,
3A4) and transporter activities, and caused steatosis over 2 weeks. Furthermore,
MPTCs secreted higher levels of pro-inflammatory interleukin-6 (IL-6) cytokine
and C-reactive protein (CRP) than MPCCs. Treatment of MPCCs with HSC-conditioned
culture medium confirmed that HSC secretions mediate the altered phenotype of
PHHs observed in MPTCs, partly via IL-6 signaling. Lastly, we found that NADPH
oxidase (NOX) inhibition and farnesoid X receptor (FXR) activation using
clinically relevant drugs alleviated hepatic dysfunctions in MPTCs. In
conclusion, MPTCs recapitulate symptoms of NASH- and early fibrosis-like
dysfunctions in PHHs and have utility for drug discovery in this space.
PMID- 28702668
TI - Effects of counter anions, P-substituents, and solvents on optical and
photophysical properties of 2-phenylbenzo[b]phospholium salts.
AB - In this work, we investigated the effects of counter anions, P-substituents, and
solvents on the optical and photophysical properties of 2
phenylbenzo[b]phospholium salts in solution. A series of 2
phenylbenzo[b]phospholium salts was prepared by P-alkylation or P-phenylation of
1,2-diphenylbenzo[b]phosphole followed by anion exchange reactions. X-ray
crystallographic analyses of six benzo[b]phospholium salts showed that each
phosphorus center has an onium nature with an essentially tetrahedral geometry.
1H NMR and steady-state UV-vis absorption and fluorescence spectroscopic
measurements of these phospholium salts revealed the pivotal role of counter
anion solvation. The observed results are discussed on the basis of the
association-dissociation equilibrium between a contact ion pair (CIP) and a
solvent-separated ion pair (SSIP) in solution. The hexafluorophosphates exist as
SSIPs and emit intense fluorescence, irrespective of the P-substituents and
solvents. In contrast, the iodides are present as SSIPs in methanol but exist as
equilibrium mixtures of the two emitting species, SSIP and CIP, in
dichloromethane. As a consequence, fluorescence intensities of the iodides varied
significantly depending on the solvents, P-substituents, and solution
concentrations. These findings were studied in more detail using time-resolved
fluorescence spectroscopy and fluorescence titration measurements. The light
emitting properties of the 2-phenylbenzo[b]phospholium halides in the CIPs rely
on heavy atom effects derived from the counter halide anions on the S1 state of
the adjacent cationic benzo[b]phosphole pi-systems. The present study suggests
that 2-arylbenzo[b]phospholium salts would be promising scaffolds for developing
new phosphole-based ionic fluorophores that are capable of responding to external
stimuli such as anionic species and solvents.
PMID- 28702669
TI - Analogous self-assembly and crystallization: a chloride-directed orientated self
assembly of Cu nanoclusters and subsequent growth of Cu2-xS nanocrystals.
AB - Self-assembly and crystallization are two common methods to control the
morphologies of nanomaterials, which have many similarities. In this work,
chloride is used to direct the self-assembly process of Cu nanoclusters and the
subsequent growth of Cu2-xS nanocrystals. Meaningfully, chloride both promotes
the transformation of Cu nanocluster self-assembled architectures from one
dimensional (1D) to 2D, and facilitates the transformation of Cu2-xS nanocrystals
from nanorods to nanosheets. Such an influence is attributed to the selective
adsorption of chloride ions on the specific facets of nanoclusters and
nanocrystals, which alters the inter-nanocluster weak interactions during self
assembly and suppresses the activity of Cu2-xS facets during nanocrystal growth.
The current results indicate that the method used to direct the morphologies of
nanocrystals is extendable to control the tendency of nanocluster self-assembly.
PMID- 28702670
TI - Lmna knockout mouse embryonic fibroblasts are less contractile than their wild
type counterparts.
AB - In order to maintain tissue homeostasis and functionality, adherent cells need to
sense and respond to environmental mechanical stimuli. An important ability that
adherent cells need in order to properly sense and respond to mechanical stimuli
is the ability to exert contractile stress onto the environment via actin stress
fibers. The actin stress fibers form a structural chain between the cells'
environment via focal adhesions and the nucleus via the nuclear lamina. In case
one of the links in this chain is missing or aberrant, contractile stress
generation will be affected. This is especially the case in laminopathic cells,
which have a missing or mutated form of the LMNA gene encoding for part of the
nuclear lamina. Using the thin film method combined with sample specific finite
element modeling, we quantitatively showed a fivefold lower contractile stress
generation of Lmna knockout mouse embryonic fibroblasts (MEFs) as compared to
wild-type MEFs. Via fluorescence microscopy it was demonstrated that the lower
contractile stress generation was associated with an impaired actin stress fiber
organization with thinner actin fibers and smaller focal adhesions. Similar
experiments with wild-type MEFs with chemically disrupted actin stress fibers
verified these findings. These data illustrate the importance of an organized
actin stress fiber network for contractile stress generation and demonstrate the
devastating effect of an impaired stress fiber organization in laminopathic
fibroblasts. Next to this, the thin film method is expected to be a promising
tool in unraveling contractility differences between fibroblasts with different
types of laminopathic mutations.
PMID- 28702671
TI - Self-assembly of porphyrin-DNA hybrids into large flat nanostructures.
AB - The main aim of nanotechnology is to create functional systems by controlling the
matter at the nanometer level. In this context DNA is a versatile building block
for the fabrication of micrometer-scale objects with a subnanometer-scale
resolution. Over the last 15 years, DNA nanotechnology has considerably developed
with the invention of DNA origami, double crossover structures and
molecule/oligonucleotide hybrids. Our interest is focused on the combination of
short complementary DNA sequences with organic molecules with a view to create
large self-assembled nanostructures. Here we report on the synthesis of porphyrin
derivatives bearing up to four 21-mer oligonucleotides and we demonstrate that
the combination of the molecular hybrids containing complementary DNA strands
leads to the formation of large nanostructures with micrometer-scale size.
PMID- 28702672
TI - Chitosan-stabilized platinum nanoparticles as effective oxidase mimics for
colorimetric detection of acid phosphatase.
AB - Capping molecules on the surface of nanomaterials not only enhance the dispersion
and stability of nanomaterials but also greatly facilitate their surface
modification and biological applications. However, most capping molecules can
severely block the active sites of the catalytic core, thereby decreasing the
enzymatic activity of nanomaterial-based enzyme mimics. This work demonstrates
the superiority of chitosan (Ch) as a capping molecule for synthesizing catalytic
platinum nanoparticles (PtNPs). The experimental results show that Ch
simultaneously exhibits an excellent stabilizing effect and enhances the oxidase
like activity of PtNPs. Kinetic studies indicate that Ch-PtNPs have a higher
affinity for 3,3',5,5'-tetramethylbenzidine (TMB) than other kinds of oxidase
mimics. Furthermore, the TMB chromogenic reaction catalyzed by Ch-PtNPs is found
to be much faster in an acidic medium, thus adapting well to the optimal pH for
acid phosphatase (ACP). Therefore, a novel colorimetric approach for ACP
determination is developed for the first time, which is based on the Ch-PtNP
catalyzed oxidation of TMB, the inhibitory effect of ascorbic acid (AA) on the
oxidase-like activity of Ch-PtNPs, and the ACP-catalyzed hydrolysis of AA 2
phosphate (AAP) into AA. The linear range for ACP is 0.25-2.5 U L-1 and the limit
of detection is measured to be 0.016 U L-1. This new colorimetric method is
utilized to detect ACP in real biological samples and to screen ACP inhibitors.
We believe that these new PtNPs, which exhibit high colloidal stability,
excellent catalytic performance, good biocompatibility, simple preparation, and
easy modification, can be promising candidates for a broad range of applications
in optical sensing, environmental monitoring, clinical diagnosis, and drug
discovery.
PMID- 28702673
TI - Unexpected thermal annealing effects on the viscosity of polymer nanocomposites.
AB - The effects of thermal annealing, 12-50 K above the glass transition temperature,
on the zero-shear viscosity, eta, of polymer nanocomposites (PNCs) and the
corresponding host polymers were studied. For all specimens, including neat and 4
wt% dioctyl phthalate (DOP)-plasticized polystyrene (PS), neat poly(methyl
methacrylate) (PMMA), and PNCs containing bare and grafted silica nanoparticles
in neat and DOP-plasticized PS, the eta increased with time initially, and only
asymptotically approached a steady-state value after thermal annealing for ~100
to ~200 h. We found that this phenomenon occurred regardless of the solvent used
to prepare the sample although the fractional changes in eta (deltaeta/eta) are
visibly bigger for tetrahydrofuran (THF). Moreover, the PNCs not plasticized by
DOP showed bigger deltaeta/eta than their host polymers while the plasticized
ones behave essentially the same as the neat hosts. Interestingly, some
unplasticized PNCs prepared from THF exhibited smaller viscosities than the host
polymer, but this anomaly disappeared on thermal annealing. By correlating the
viscosity measurements with the evolution of the solvent content, average NP
aggregate size and the amount of adsorbed PS on silica for samples prepared from
different solvents, we infer that the temporal viscosity evolution originates
from out-of-equilibrium chain conformations produced during sample preparation.
Because these relaxations are limited by the rearrangement of the polymer chains
adsorbed on the NP or sample substrate surface, the timescales over which eta
changes can be much longer than the polymer reptation time, as observed.
PMID- 28702674
TI - Report From the NEI/FDA Endpoints Workshop on Age-Related Macular Degeneration
and Inherited Retinal Diseases.
PMID- 28702675
TI - TNF-alpha Genetic Predisposition and Higher Expression of Inflammatory Pathway
Components in Keratoconus.
AB - Purpose: To date keratoconus (KC) pathogenesis is undefined; however, the
involvement of inflammatory pathways in disease development is becoming apparent.
In the present study, we investigated the role of a promoter region polymorphism
rs1800629 (-308G>A) in the inflammatory pathway component TNF-alpha and its
effects on the expression of TNF-alpha and downstream molecules tumor necrosis
factor receptor 1 and 2 (TNFR1 and TNFR2), v-rel avian reticuloendotheliosis
viral oncogene homolog A (RELA), and interleukin 6 (IL-6) in KC development.
Methods: TNF-alpha promoter polymorphism rs1800629 (-308G>A), was genotyped in
257 sporadic KC patients and 253 healthy controls. Enzyme-linked immunosorbent
assay (ELISA) was performed to assess for the -308G>A genotypes. Quantitative
polymerase chain reaction (qPCR) was carried out to compare the mRNA expression
of TNF-alpha, TNFR1, TNFR2, RELA, and IL6 in the corneal tissues of 20 KC
patients and 20 donor controls. Results: The -308G>A genotype GA was found to be
significantly associated with KC development (dominant model [odds ratio (OR) =
6.67 (95% confidence interval [CI] = 4.28-10.42), P < 0.001]) and allele-A (OR =
4.30, 95%CI = 2.93-6.34, P < 0.001). TNF-alpha serum levels were significantly
raised in patients with GA genotype (196.5 +/- 69.5 pg/mL) compared to reference
genotype GG (21.7 +/- 8.2 pg/mL) (P < 0.0001). There was a significant
overexpression of TNF-alpha (P = 0.002), TNFR2 (P = 0.0001), RELA (P = 0.0117),
and IL6 (P = 0.0007) in the KC corneal tissues as compared to the control.
Conclusions: The GA genotype of the TNF-alpha -308G>A polymorphism is a
significant genetic risk factor for the pathogenesis of KC. Moreover, this single
nucleotide polymorphism (SNP) was observed to be associated with deregulated
expression of downstream molecules, thus further reinforcing the role of the
inflammatory pathway components in the development of KC.
PMID- 28702676
TI - Prevalence and Risk Factors for Nonexudative Neovascularization in Fellow Eyes of
Patients With Unilateral Age-Related Macular Degeneration and Polypoidal
Choroidal Vasculopathy.
AB - Purpose: To determine the prevalence of subclinical nonexudative
neovascularization and associated choroidal vascular changes in the fellow eyes
of patients presenting with unilateral typical exudative AMD (tAMD) or polypoidal
choroidal vasculopathy (PCV) using indocyanine green angiography (ICGA) and swept
source (SS) optical coherence tomography angiography (OCT-A). Methods: We
recruited patients presenting with tAMD or PCV in a prospective clinical study.
The diagnosis in the presenting eye was determined based on clinical, fluorescein
angiography (FA), and ICGA findings. We evaluated the contralateral eye for
presence of nonexudative neovascularization, choroidal hyperpermeability, and
pachyvessels in the outer choroid, based on multimodal imaging which included
ICGA, spectral-domain (SD) OCT and OCT-A. We measured subfoveal choroidal
thickness in both eyes for each patient. Results: We included 76 fellow eyes of
76 patients who presented with unilateral tAMD (n = 33) or PCV (n = 43).
Nonexudative neovascularization was present in 18% eyes (14 eyes, 8 in tAMD
group, 6 in PCV group; 7 on ICGA, 4 on OCT-A, 3 on both ICGA and OCT-A).
Pachychoroid pigment epitheliopathy was present in 13 eyes with nonexudative
neovascularization, and was the only risk factor associated with nonexudative
neovascularization. Conclusions: Approximately one in five fellow eyes with
unilateral tAMD and PCV have features of nonexudative neovascularization. The use
of multimodal imaging including ICGA and OCT-A can identify these features. The
presence of pachychoroid epitheliopathy should alert clinicians to the
possibility of underlying neovascularization.
PMID- 28702677
TI - Shortened Nonword Repetition Task (NWR-S): A Simple, Quick, and Less Expensive
Outcome to Identify Children With Combined Specific Language and Reading
Impairment.
AB - Purpose: The purpose of this research note was to validate a simplified version
of the Dutch nonword repetition task (NWR; Rispens & Baker, 2012). The NWR was
shortened and scoring was transformed to correct/incorrect nonwords, resulting in
the shortened NWR (NWR-S). Method: NWR-S and NWR performance were compared in the
previously published data set of Rispens and Baker (2012; N = 88), who compared
NWR performance in 5 participant groups: specific language impairment (SLI),
reading impairment (RI), both SLI and RI, one control group matched on
chronological age, and one control group matched on language age. Results:
Analyses of variance showed that children with SLI + RI performed significantly
worse than other participant groups in NWR-S, just as in NWR. Logistic regression
analyses showed that both tasks can predict an SLI + RI outcome. NWR-S holds a
sensitivity of 82.6% and a specificity of 95.4% in identifying children with SLI
+ RI. The sensitivity of the original NWR is 87.0% with a specificity of 87.7%.
Conclusions: As the original NWR, the NWR-S comprising a subset of 22 nonwords
scored with a simplified scoring system can identify children with combined SLI
and RI while saving a significant amount of the needed assessment time.
Supplemental Materials: https://doi.org/10.23641/asha.5150116.
PMID- 28702679
TI - Predictive factors of bleeding among pediatric patients undergoing percutaneous
nephrolithotomy.
AB - The purpose of this study is to determine the perioperative risk factors for
increased blood loss in children undergoing percutaneous nephrolithotomy
(PCNL).We retrospectively reviewed the data on pediatric patients who had
undergone PCNL for stone disease in our department. Blood loss estimation was
quantified by measuring the changes in hematocrit plus the volume of red blood
cells transfused. Univariate and multivariate linear regression analyses were
performed to evaluate risk factors associated with increased blood loss after
pediatric PCNL. Variables included patient, stone, and treatment parameters. The
study group consisted of 105 renal units in 97 children with a median
(interquartile range) age of 5 (3-9) years. On univariate linear regression
analysis female gender (p = 0.030), absence of hydronephrosis (p = 0.013),
increasing stone burden (p = 0.002), staghorn stone type (p = 0.013), multi-tract
access (p < 0.001), and prolonged operative time (p < 0.001) were significantly
associated with increased blood loss after pediatric PCNL. However, multivariate
linear regression analysis demonstrated that the only independent risk factors
for increased blood loss following pediatric PCNL were degree of hydronephrosis
(B -1.329, 95% CI -2.451 to -0.208, p = 0.021), number of tracts (B 2.545, 95% CI
0.221-4.869, p = 0.032), and operative time (B 0.031, 95% CI 0.008-0.053, p =
0.007). Identifying pediatric patients at increased risk of bleeding following
PCNL is crucial to minimize morbidity and hospital stay, and thus, the cost of
treatment. Our study demonstrated that degree of hydronephrosis, number of tracts
and operative time are important factors in reducing blood loss during pediatric
PCNL.
PMID- 28702680
TI - Greetings from Your New Editor-in-Chief.
PMID- 28702681
TI - Intra-arterial Thrombolysis for Extremity Frostbite Decreases Digital Amputation
Rates and Hospital Length of Stay.
AB - PURPOSE: To report outcomes of intra-arterial thrombolysis versus non
thrombolytic management of severe frostbite with respect to digital amputation
rates and hospital length of stay (LOS). MATERIALS AND METHODS: Seventeen
patients with severe frostbite were identified from 2000 to 2017. Eight (47%)
patients with mean age of 40 years underwent intra-arterial thrombolysis and
served as the treatment group. Nine (53%) patients with mean age of 53 years
received non-thrombolytic management and served as the control group. 2/8 (25%)
treatment and 3/9 (33%) control patients had underlying vascular comorbidities (p
= 0.25). Number of digits at risk, duration of thrombolysis, thrombolytic agents
used, digits amputated, hospital LOS, and complications were recorded. RESULTS:
Seven upper and nine lower extremities for a total of 80 digits were at risk in
the treatment cohort. Eight upper and 12 lower extremities for a total of 100
digits were at risk in the control group. Mean duration of thrombolysis was 26 h.
All treatment patients received tissue plasminogen activator in addition to
systemic heparin. 4/16 (25%) limbs received intra-arterial alprostadil, 2/16
(13%) received nitroglycerin, and 2/16 (13%) received nicardipine. 12/80 (15%)
treatment digits and 77/100 (77%) control digits required amputation (p = 0.003).
Average hospital LOS was 14 days in the treatment group and 38 days in the
control group (p = 0.011). No major complications occurred in the treatment
group; however, 2/9 (22%) patients in the control group required extended
hospitalizations secondary to amputation complications. CONCLUSIONS: Intra
arterial thrombolysis reduces digital amputation rates and hospital LOS in the
setting of severe frostbite.
PMID- 28702682
TI - Abdominal obesity and risk of hip fracture: a meta-analysis of prospective
studies.
AB - : We conducted a meta-analysis to qualitatively summarize the evidence of the
association between abdominal obesity and hip fracture risk. The results
indicated that abdominal obesity as measured by waist circumference and waist-hip
ratio might be associated with an increased risk of hip fracture. INTRODUCTION:
Epidemiological investigations evaluating the association of abdominal obesity
with hip fracture risk have yielded conflicting results. Therefore, a meta
analysis was conducted to qualitatively summarize the evidence of the
associations between waist circumference, waist-hip ratio, and hip circumference
and the risk of hip fracture, respectively. METHODS: PubMed, Embase, and Web of
Science were searched for relevant articles published up to March 2017. Pooled
relative risks (RRs) with 95% confidence intervals (CIs) were calculated with a
random-effects model. Dose-response relationship was assessed by restricted cubic
spline. RESULTS: Seven studies involving 180,600 participants for hip
circumference, six studies involving 199,828 participants for waist-hip ratio,
and five studies involving 170,796 participants for waist circumference were
finally included in this meta-analysis. The combined RRs with 95% CIs of hip
fracture for the highest versus lowest category of waist circumference, waist-hip
ratio, and hip circumference were 1.58 (95% CI 1.20-2.08), 1.32 (95% CI 1.15
1.52), and 0.87 (95% CI 0.74-1.02), respectively. For dose-response analysis, a
nonlinear relationship was found (P nonlinearity < 0.001) between waist
circumference and the risk of hip fracture, and a linear relationship (P
nonlinearity = 0.911) suggested that the risk of hip fracture increased about
3.0% (1.03 (1.01-1.04)) for each 0.1 unit increment of waist-hip ratio.
CONCLUSIONS: This meta-analysis suggested that abdominal obesity as measured by
waist circumference and waist-hip ratio might be associated with an increased
risk of hip fracture. From a public health perspective, indicators of abdominal
obesity may be usable predictors of hip fracture risk.
PMID- 28702684
TI - A predictive model of inflammatory markers and patient-reported symptoms for
cachexia in newly diagnosed pancreatic cancer patients: methodological issues to
avoid misinterpretation.
PMID- 28702683
TI - Blood on the tracks: hematopoietic stem cell-endothelial cell interactions in
homing and engraftment.
AB - Cells of the hematopoietic system undergo rapid turnover. Each day, humans
require the production of about one hundred billion new blood cells for proper
function. Hematopoietic stem cells (HSCs) are rare cells that reside in
specialized niches and are required throughout life to produce specific
progenitor cells that will replenish all blood lineages. There is, however, an
incomplete understanding of the molecular and physical properties that regulate
HSC migration, homing, engraftment, and maintenance in the niche. Endothelial
cells (ECs) are intimately associated with HSCs throughout the life of the stem
cell, from the specialized endothelial cells that give rise to HSCs, to the
perivascular niche endothelial cells that regulate HSC homeostasis. Recent
studies have dissected the unique molecular and physical properties of the
endothelial cells in the HSC vascular niche and their role in HSC biology, which
may be manipulated to enhance hematopoietic stem cell transplantation therapies.
PMID- 28702685
TI - Durable usage of patient-reported outcome measures in clinical practice to
monitor health-related quality of life in head and neck cancer patients.
AB - PURPOSE: To investigate the long-term follow-up (5 years) of implementing patient
reported outcome measures (PROMs) in clinical practice to monitor health-related
quality of life (HRQOL) in head and neck cancer (HNC) patients. METHODS: A mixed
method design was used. The usage rate of OncoQuest (a touch screen computer
system to monitor HRQOL) and the subsequent nurse consultation was calculated
among HNC patients who visited the outpatient clinic for regular follow-up, as
well as differences between ever users and never users (sociodemographic and
clinical characteristics). The content of the nurse consultation was
investigated. Reasons for not using (barriers) or using (facilitators) OncoQuest
and the nurse consultation were explored from the perspective of HNC patients,
and of head and neck surgeons. RESULTS: Usage rate of OncoQuest was 67% and of
the nurse consultation 79%. Usage of OncoQuest was significantly related to tumor
subsite and tumor stage. Topics most frequently (>40%) discussed during the nurse
consultation were global quality of life (97%), head and neck cancer related
symptoms (82%), other physical symptoms such as pain (61%), and psychological
problems such as anxiety (44%). Several barriers and facilitators to implement
PROMs in clinical practice were reported by both patients and head and neck
surgeons. CONCLUSION: Usage of PROMs in clinical practice and a nurse
consultation is durable, even 5 years after the introduction. This study
contributes to better insight into long-term follow-up of implementation, thereby
guiding future research and projects that aim to implement PROMs in clinical
practice to monitor HRQOL among (head and neck) cancer patients.
PMID- 28702686
TI - Disparities in epilepsy surgery in the United States of America.
AB - The aim is to describe the epidemiology of epilepsy surgery in children and
adults in the United States. We performed a descriptive study of the National
Inpatient Sample (NIS) for the year 2012 and the Kids' Inpatient Database (KID)
for the period 2010-2012, the largest all-payer databases on inpatient data in
the USA. These databases estimate 97% of all inpatient hospital discharges in the
USA. In the KID, 12,899 (0.2%) of admission records had brain surgery and 600 of
the 4900 (12.2%) admissions with focal refractory epilepsy underwent epilepsy
surgery. Epilepsy surgery occurred in 60% of Whites, 7% of Blacks, 15% of
Hispanics, and 10% of other races. In the NIS, 99,650 (0.3%) of admission records
had brain surgery and 1170 of the 9775 (12%) admissions with focal refractory
epilepsy underwent epilepsy surgery. Epilepsy surgery occurred in 69% of Whites,
7% of Blacks, 9% of Hispanics, and 8% of other races. In both the KID and the
NIS, lower socioeconomic status was mildly underrepresented in epilepsy surgery.
In both pediatric and adult admissions, there was an overrepresentation of Whites
and underrepresentation of Blacks, which persisted after stratifying by
socioeconomic status. Females were underrepresented in epilepsy surgery, but
gender disparities were partially explained by differences in socioeconomic
status. Epilepsy surgery is not equally distributed across races in the USA and
these differences are not fully attributable to differences in socioeconomic
status. Racial disparities in epilepsy surgery similarly affect children and
adults.
PMID- 28702687
TI - [Phlebology].
PMID- 28702688
TI - Pseudomonas aestus sp. nov., a plant growth-promoting bacterium isolated from
mangrove sediments.
AB - Strain CMAA 1215T, a Gram-reaction-negative, aerobic, catalase positive, polarly
flagellated, motile, rod-shaped (0.5-0.8 * 1.3-1.9 um) bacterium, was isolated
from mangrove sediments, Cananeia Island, Brazil. Analysis of the 16S rRNA gene
sequences showed that strain CMAA 1215T forms a distinct phyletic line within the
Pseudomonas putida subclade, being closely related to P. plecoglossicida ATCC
700383T, P. monteilii NBRC 103158T, and P. taiwanensis BCRC 17751T of sequence
similarity of 98.86, 98.73, and 98.71%, respectively. Genomic comparisons of the
strain CMAA 1215T with its closest phylogenetic type strains using average
nucleotide index (ANI) and DNA:DNA relatedness approaches revealed 84.3-85.3% and
56.0-63.0%, respectively. A multilocus sequence analysis (MLSA) performed
concatenating 16S rRNA, gyrB and rpoB gene sequences from the novel species was
related with Pseudomonas putida subcluster and formed a new phylogenetic lineage.
The phenotypic, physiological, biochemical, and genetic characteristics support
the assignment of CMAA 1215T to the genus Pseudomonas, representing a novel
species. The name Pseudomonas aestus sp.nov. is proposed, with CMAA 1215T (=NRRL
B-653100T = CBMAI 1962T) as the type strain.
PMID- 28702689
TI - Molecular responses to recurrent drought in two contrasting rice genotypes.
AB - MAIN CONCLUSION: The set of variables analyzed as integrated by multivariate
analysis of principal components consistently showed a memory effect induced by
the drought pre-treatment in AN Cambara plants. The effects of drought can vary
ddepending on many factors. Among these the occurrence of a previous water stress
may leave a residual effect (memory), influencing the future performance of a
plant in response to a new drought event. This study tested the hypothesis that
plants experiencing recurrent drought would show more active mechanisms of water
deficit tolerance, mainly plants of the genotype that is cultivated often
experiencing water shortages periods. Additionally, all the plants subjected to
water deficit were rehydrated by 24 h and the expression of transcription factors
related to drought responses was re-evaluated. To this end, the water status of
two rice genotypes, BRS Querencia (flooded) and AN Cambara (dryland), was
evaluated to identify molecular alterations likely underpinning drought-memory.
In growth stage V5, some plants were exposed to water stress (10% VWC soil
moisture-pre-treatment). Thereafter, the pots were rehydrated at the same level
as the control pots and maintained under this condition until drought was
reapplied (10% VWC) at the reproductive stage (R1-R2). Then, the plants were
rehydrated and maintained at pot capacity for 24 h. Overall, the set of variables
analyzed integrally by multivariate analysis of principal components consistently
showed a memory effect induced by the drought pre-treatment in AN Cambara plants
(the dryland genotype). This conclusion, based on data of the biochemical and
molecular analyses, was supported by the greater capacity of maintenance of the
water status by stomatal regulation of the pre-treated and rehydrated plants
after the second drought stimulus.
PMID- 28702690
TI - Molecular mapping and candidate gene analysis of a new epicuticular wax locus in
sorghum (Sorghum bicolor L. Moench).
AB - KEY MESSAGE: A new epicuticular wax (bloom) locus has been identified and fine
mapped to the 207.89 kb genomic region on chromosome 1. A putative candidate
gene, Sobic.001G269200, annotated as GDSL-like lipase/acylhydrolase, is proposed
as the most probable candidate gene involved in bloom synthesis/deposition.
Deposition of epicuticular wax on plant aerial surface is one strategy that
plants adapt to reduce non-transpiration water loss. Epicuticular wax (bloom)
less mutants in sorghum with their glossy phenotypes exhibit changes in the
accumulation of epicuticular wax on leaf and culm surfaces. We report molecular
mapping of a new sorghum locus, bloomless mutant (bm39), involved in epicuticular
wax biosynthesis in sorghum. Inheritance studies involving a profusely bloom
parent (BTx623) and a spontaneous bloomless mutant (RS647) indicated that the
parents differed in a single gene for bloom synthesis. Bloomless was recessive to
bloom deposition. Genetic mapping involving F2 and F7 mapping populations in
diverse genetic backgrounds (BTx623 * RS647; 296A * RS647 and 27A * RS647)
identified and validated the map location of bm39 to a region of 207.89 kb on
chromosome 1. SSR markers, Sblm13 and Sblm16, flanked the bm39 locus to a map
interval of 0.3 cM on either side. Nine candidate genes were identified, of which
Sobic.001G269200 annotated for GDSL-like lipase/acylhydrolase is the most likely
gene associated with epicuticular wax deposition. Gene expression analysis in
parents, isogenic lines and sets of near isogenic lines also confirmed the
reduced expression of the putative candidate gene. The study opens possibilities
for a detailed molecular analysis of the gene, its role in epicuticular wax
synthesis and deposition, and may help to understand its function in moisture
stress tolerance and insect and pathogen resistance in sorghum.
PMID- 28702691
TI - Toxic effects and biodistribution of ultrasmall gold nanoparticles.
AB - Gold nanoparticles (AuNPs) have been extensively explored in biomedical
applications, for example as drug carriers, contrast agents, or therapeutics.
However, AuNP can exhibit cytotoxic profile, when the size is below 2 nm
(ultrasmall AuNP; usAuNP) and when the stabilizing ligands allow for access to
the gold surface either for the direct interaction with biomolecules or for
catalytic activity of the unshielded gold surface. Furthermore, usAuNP exhibits
significantly different biodistribution and enhanced circulation times compared
to larger AuNP. This review gives an overview about the synthesis and the physico
chemical properties of usAuNP and, thereby, focusses on 1.4 nm sized AuNP, which
are derived from the compound Au55(PPh3)12Cl6 and which are the most intensively
studied usAuNP in the field. This part is followed by a summary of the toxic
properties of usAuNP, which include in vitro cytotoxicity tests on different cell
lines, electrophysiological tests following FDA guidelines as well as studies on
antibacterial effects. Finally, the biodistribution and pharmacokinetics of
ultrasmall AuNP are discussed and compared to the properties of more
biocompatible, larger AuNP.
PMID- 28702692
TI - Reply to the Commentary by Lotti M. and Moretto A. "Organophosphate neurotoxicity
to the voluntary motor system on the trail of environment-caused amyotrophic
lateral sclerosis: the known, the misknown and the unknown.
PMID- 28702693
TI - [Ultrasonography of the prostate gland : From B-image through multiparametric
ultrasound to targeted biopsy].
AB - BACKGROUND: Prostate cancer is the most frequent cancer in men. The diagnosis is
normally achieved by a systematic prostate biopsy; however, this is a randomized
approach by which a substantial number of significant carcinomas go undetected.
For this reason, in recent years imaging techniques have been continuously
developed, which enable visualization and therefore targeted biopsies. STANDARD
PROCEDURE: The use of systematic biopsies is a standard procedure for the
detection of prostate cancer. The quality of biopsies can be increased if the
prostate is examined for the presence of suspected cancerous alterations during
the biopsy. This can be carried out using multiparametric transrectral
ultrasound. PERFORMANCE: Multiparametric ultrasound within the framework of a
targeted biopsy increases the detection rate of significant prostate carcinomas
with a simultaneous decrease in detection of insignificant carcinomas; however,
the diagnostic reliability and the evidence level of multiparametric transrectal
ultrasound are not yet sufficiently high to be able to replace a systematic
biopsy. CONCLUSION: In the hands of a well-trained examiner multiparametric
transrectal ultrasound represents a good method for detection of prostate
carcinomas. With the progression in technical developments of ultrasound
technology, the detection rate will presumably be further increased.
PMID- 28702694
TI - Mortality and morbidity in oesophageal atresia.
AB - BACKGROUND: Several classification systems exist to predict mortality in
oesophageal atresia, the most widely quoted of these being over 20 years old. No
classification system exists to predict morbidity. We sought to test whether
these classification systems remain relevant and to determine whether they can be
useful to predict morbidity. In addition, we aimed to identify independent risk
factors for predicting mortality and morbidity. METHODS: Neonates presenting with
oesophageal atresia over a 20-year period (1990-2010) were retrospectively
reviewed. Discriminative statistical analysis compared the performance of current
classification systems. Stepwise logistic regression analysis of the influence of
perioperative risk factors on mortality and duration of ventilatory support and
intensive care unit stay were performed. RESULTS: All classification systems
predicted mortality in this series of 248 neonates. Birth weight, cardiac
anomalies and pre-operative pneumonia were independent risk factors for
predicting mortality in oesophageal atresia. The Waterston classification is the
most useful classification for predicting post-operative morbidity in terms of
length of hospital stay and time spent ventilated. CONCLUSION: Despite advances
in the neonatal care of the very low birth weight infant and those with
congenital cardiac disease, these conditions remain relevant in predicting
mortality and morbidity in oesophageal atresia.
PMID- 28702695
TI - Erratum to: The Puzzle of Male Chronophilias.
PMID- 28702696
TI - Mapping diurnal changes in choroidal, Haller's and Sattler's layer thickness
using 3-dimensional 1060-nm optical coherence tomography.
AB - PURPOSE: To test the significance of diurnal changes in choroidal, Haller's and
Sattler's layer thickness in healthy subjects using spatial analysis of three
dimensional (3D) 1060-nm optical coherence tomography (OCT) scans. METHODS:
Automatically generated choroidal, Haller's and Sattler's layer thickness maps
were statistically analyzed for 19 healthy subjects at two time points (8 a.m.
and 6 p.m.) that represent the currently proposed ChT peak and nadir. All
subjects were imaged by high-speed 1060-nm OCT over a 36 degrees * 36 degrees
field of view. Spatial distribution of layer thickness was analyzed using the
Early Treatment Diabetic Retinopathy Study (ETDRS) grid. RESULTS: The choroid was
significantly thicker at 8 a.m. than at 6 p.m. (p < 0,0125, paired t-test,
Bonferroni correction). Diurnal variation of mean choroidal thickness (ChT) for
all ETDRS subfields was 12 MUm. Haller's layer thickness showed no significant
diurnal variation (P > 0.0125), but Sattler's layer was thicker in the morning
than in late afternoon (P < 0.0125). CONCLUSIONS: Our measurements indicate that
diurnal ChT variation may exist, but is less relevant than previously proposed by
studies using single location imaging. Sattler's layer shows diurnal variation in
line with ChT.
PMID- 28702697
TI - The acute effect of strength exercises at different intensities on intraocular
pressure.
AB - BACKGROUND: This study aimed to determine the effect of two basic strength
exercises with progressive loads on intraocular pressure (IOP). METHODS:
Seventeen (out of 20 recruited) physically active male military officers (46 +/-
4.77 years) performed the jump squat and the ballistic bench press exercises, in
counterbalanced order, with four and five progressive loads, respectively. IOP
was measured with a rebound tonometer before and after each of the corresponding
loads. RESULTS: IOP linearly increases with heavier loads for the jump squat (r =
0.976) and the ballistic bench press (r = 0.991) exercises. A significant IOP
elevation was observed during the jump squat test (p < 0.001), and Bonferroni
Holm correction revealed that ~75% of one repetition maximum (RM) was able to
promote significant changes in IOP with respect to the other three loads (all
corrected p values <0.05), whereas the load corresponding to ~65%RM and ~60%RM
induced a significant IOP rise when compared with the load of ~50%RM (corrected p
values of 0.43 in both cases). For its part, IOP significantly increases with the
bench press test (p < 0.001), and performing the ~50%RM load was enough to induce
significant IOP changes (corrected p-value <0.01). CONCLUSIONS: Acute performance
of jump squat and ballistic bench press lead to a significant increase of IOP,
and 5 min of rest are enough to recover baseline IOP values. There is a strong
linear association between the increase in load and the IOP rise for both
exercises, and bench press execution produces a significantly higher IOP increase
when compared with the jump squat for the same relative loads.
PMID- 28702698
TI - Principles of first trimester screening in the age of non-invasive prenatal
diagnosis: screening for chromosomal abnormalities.
AB - PURPOSE: First trimester risk assessment for chromosomal abnormalities plays a
major role in the contemporary pregnancy care. It has evolved significantly since
its introduction in the 1990s, when it essentially consisted of just the nuchal
translucency measurement. Today, it involves the measurement of several
biophysical and biochemical markers and it is often combined with a cell-free DNA
(cfDNA) analysis as a secondary test. METHODS: A search of the Medline and Embase
databases was done looking for articles about first trimester aneuploidy
screening. We performed a detailed review of the literature to evaluate the
screening tests currently available and their respective test performance.
RESULTS: Combined screening for trisomy 21 based on maternal age, fetal NT, and
the serum markers free beta-hCG and PAPP-A results in a detection rate of about
90% for a false positive of 3-5%. With the addition of further ultrasound
markers, the false positive rate can be roughly halved. Screening based on cfDNA
identifies about 99% of the affected fetuses for a false positive rate of 0.1%.
However, there is a test failure rate of about 2%. The ideal combination between
combined and cfDNA screening is still under discussion. Currently, a contingent
screening policy seems most favorable where combined screening is offered for
everyone and cfDNA analysis only for those with a borderline risk result after
combined screening. CONCLUSION: Significant advances in screening for trisomy 21
have been made over the past 2 decades. Contemporary screening policies can
detect for more than 95% of affected fetuses for false positive rate of less than
3%.
PMID- 28702699
TI - Work-related musculoskeletal injuries amongst obstetrics and gynaecology trainees
in East Midland region of the UK.
AB - PURPOSE: Work-related musculoskeletal injuries (WRMSI) have been well known
amongst obstetrics and gynaecology (O&G) practitioners, but limited data have
been reported. Our aim is to determine the prevalence, severity and
characteristics of WRMSI amongst O&G trainees. METHODS: A musculoskeletal
ergonomic survey was conducted amongst the O&G trainees in the East-Midlands
region of United Kingdom (UK). The survey comprised of demographic details, year
of training, previous manual handling training, any work-related orthopaedic
injury, the type of injury, any treatment received in addition to any sick leave
incurred after the injury were also documented. RESULTS: The response rate for
the survey was 76% (59/78). The majority (22%) were senior specialist trainee,
seventh year (ST7) and between 30 and 34 age groups. Approximately 90% of the
trainees reported to have experienced pain in the last year. The most common site
was the back, which was followed by the shoulders and the upper limbs. 63% of
trainees reported injuries that were attributed to WRMSI. One in ten of the
trainees needed time off work due to injury. A total of 20 days were lost in the
last 12 months as a result of pain or discomfort attributed to obstetric work.
CONCLUSIONS: Our results demonstrate the prevalence of work-related injuries and
its detrimental effects. Such injuries are underreported on incident reporting
system. Ergonomics and WRMSI prevention in obstetrics and gynaecology is an area
seldom discussed. Obstetric training sessions should incorporate ergonomic
interventions. Further research is required to establish relevant aetiological
factors related to WRMSI in this specialty.
PMID- 28702700
TI - Clinical and radiological outcomes after reverse shoulder arthroplasty with less
medialized endoprosthesis after mean follow-up time of 45 months.
AB - INTRODUCTION: The purpose of this study was to evaluate outcomes after reverse
shoulder arthroplasty for the treatment of complex three- and four-fragment
proximal humeral fractures after mean follow-up time of 45 months and to compare
our results with the results published by other authors. MATERIALS AND METHODS:
Retrospectively we have analyzed 27 consecutive patients after total arthroplasty
with less medialized reverse shoulder prosthesis used for the treatment of
complex proximal humeral fracture. The median age and standard deviation was 67.5
+/- 7.3 years (range 55-85). The average follow-up time was 45 months. Shoulder
function was evaluated using Simple Shoulder Test and Constant scale. Patient
satisfaction about the treatment was evaluated using Likert-type questionnaire.
All patients were investigated radiologically for possible complications using
standard lateral and anterior views. RESULTS: All patients were satisfied (74%)
or highly satisfied (26%). The mean total Constant-Murley score was 57.6 pts.
(range 37.4-80.2). Mean total Simple Shoulder Test score was 73.5 pts. (range
49.8-100). There were two cases with heterotopic ossification and one with
greater tubercle malposition. We found no signs of scapular notching, implant
failure or loosening. CONCLUSIONS: Results after reverse arthroplasty for complex
proximal humeral fractures yield good clinical, functional, and radiological
outcomes after mean follow-up time of 45 months. Results are comparable to other
studies published in the recent literature.
PMID- 28702701
TI - Neighbor effect and local conformation in protein structures.
AB - In order to determine the preference or avoidance of the first and second
positions of individual dipeptides for adopting different structural
conformations, we randomly select defined structural groups of proteins from
protein data bank and statistically analyzed the distribution of all 400 possible
dipeptides in different secondary structural elements. Considering different
combinations of alpha-helix (alpha), beta strand (beta) and coil (c) including
alphaalpha, alphabeta, alphac, betabeta, betaalpha, betac, cc, calpha, cbeta
conformations, we found that some dipeptides are randomly distributed in these
conformations, while others have non-random distribution for a given
conformation. Finally, we provide new set of data containing preference and
avoidance tendencies that originate from the neighbor effect for each amino acid
according to the context of secondary structural element. The output of current
work can provide novel data for different fields of structural bioinformatics as
well as experiments involving site-directed mutagenesis.
PMID- 28702702
TI - [Placebo and nocebo : How can they be used or avoided?]
AB - The expectations of patients enhance the probability of their occurrence and are
thereby the main triggers for inducing placebo and nocebo responses. Strong
placebo effects are not only regularly observed in pharmaceutical and non
pharmaceutical sham treatment in placebo controlled studies but also make a
considerable contribution to any real treatment. The accompanying words are
essential to ensure maximum impact of drugs and other forms of treatment. They
should contain positive expressions instead of negations. Such a strengthening of
drug therapy by placebo effects is more important than the widespread use of
placebos that remains a problem because of the obligation to provide information
and effective therapy and because of inherently induced side effects. Any false
comments about symptoms or side effects can aggravate or induce them. Nocebo
effects are not imagined but real symptoms that can definitely be harmful. They
constitute a considerable proportion of the side effects requiring treatment.
Awareness and knowledge is needed to prevent or neutralize them. Nocebo effects
are avoidable when risk information is always directly combined with positive
aspects, such as the expected benefits of the treatment or the prophylactic
measures and therapeutic options for side effects. Existing negative expectations
are disrupted by providing more alternative options and by leaving negative
experiences in the past where they belong. Placebo and nocebo effects are
strongly sensitive to the context. They are dependent on the experiences and
conceptions of the individual patient, as well as on the physician-patient
relationship. The latter can provide the best protection against harm from risk
disclosure. In addition, the expectations of patients and their consequences are
strongly affected by the expectations of the treating doctor, by fellow patients,
the media and society.
PMID- 28702703
TI - Transfixing Kirshner wires for fixation of intertrochanteric valgus osteotomies
in management of pediatric coxa vara.
AB - BACKGROUND: Coxa vara is a radiological term describing a decrease in the neck
shaft angle to 120 degrees or less. Coxa vara is associated with pathomechanical
changes that can manifest clinically. If left untreated, coxa vara can affect the
normal development of the pediatric hip. Valgus osteotomy is the standard
surgical treatment for coxa vara, but there is no consensus regarding the optimal
osteotomy technique and fixation method. The work reported here aimed to
highlight transfixing wires as a fixation method for valgus osteotomy applied as
treatment for various types of pediatric coxa vara. MATERIALS AND METHODS: This
study included 16 cases of pediatric coxa vara with different etiologies in 9
patients with a mean age of 39.9 +/- 15.2 months. Radiological and clinical
evaluations and scoring of the condition of each patient according to the Iowa
Hip Score were performed pre- and postoperatively. Transfixing wires and a
protective spica were used for the fixation of a V-shaped, laterally based,
closing-wedge valgus osteotomy in all cases. The postoperative follow-up period
ranged from 14 to 102 months, with a mean duration of 33.3 +/- 27.7 months.
RESULTS: The mean Hilgenreiner epiphyseal angle (HEA) was corrected from 81.7 +/-
2.2 degrees to 24.3 +/- 3.5 degrees and the mean femoral neck-shaft angle
(FNSA) was improved from 86.9 +/- 4.2 degrees to 138.6 +/- 3.5 degrees . No
recurrence of the deformity was observed during the follow-up periods considered
here. The osteotomy site united after an average of 11.7 +/- 2.2 weeks with no
secondary displacement, and in cases of developmental coxa vara there was
progressive ossification of the neck defect with no surgery-related
complications. Clinical results were markedly improved by the osteotomy, with a
mean postoperative Iowa Hip Score at last follow-up of 95.06 +/- 2.6, compared to
a mean preoperative score of 57.4 +/- 3.6. CONCLUSIONS: Transfixing wires
protected in a hip spica cast represent a simple, easy, and reliable fixation
method for valgus osteotomies performed to correct pediatic coxa vara. It assures
stable fixation and rapid healing of the osteotomy without loss of the achieved
correction, it completely avoids the femoral neck affording marked protection to
the growth plate. LEVEL OF EVIDENCE: IV.
PMID- 28702704
TI - Ezrin Orchestrates Signal Transduction in Airway Cells.
AB - Ezrin is a critical structural protein that organizes receptor complexes and
orchestrates their signal transduction. In this study, we review the ezrin
meditated regulation of critical receptor complexes, including the epidermal
growth factor receptor (EGFR), CD44, vascular cell adhesion molecule (VCAM), and
the deleted in colorectal cancer (DCC) receptor. We also analyze the ezrin
meditated regulation of critical pathways associated with asthma, such as the
RhoA, Rho-associated protein kinase (ROCK), and protein kinase A (cAMP/PKA)
pathways. Mounting evidence suggests that ezrin plays a role in controlling
airway cell function and potentially contributes to respiratory diseases. Ezrin
can participate in asthma pathogenesis by affecting bronchial epithelium repair,
T lymphocyte regulation, and the contraction of the airway smooth muscle cells.
These studies provide new insights for the design of novel therapeutic strategies
for asthma treatment.
PMID- 28702705
TI - Wolbachia in the Genus Bicyclus: a Forgotten Player.
AB - Bicyclus butterflies are key species for studies of wing pattern development,
phenotypic plasticity, speciation and the genetics of Lepidoptera. One of the key
endosymbionts in butterflies, the alpha-Proteobacterium Wolbachia pipientis, is
affecting many of these biological processes; however, Bicyclus butterflies have
not been investigated systematically as hosts to Wolbachia. In this study, we
screen for Wolbachia infection in several Bicyclus species from natural
populations across Africa as well as two laboratory populations. Out of the 24
species tested, 19 were found to be infected, and no double infection was found,
but both A- and B-supergroup strains colonise this butterfly group. We also show
that many of the Wolbachia strains identified in Bicyclus butterflies belong to
the ST19 clonal complex. We discuss the importance of our results in regard to
routinely screening for Wolbachia when using Bicyclus butterflies as the study
organism of research in eco-evolutionary biology.
PMID- 28702706
TI - Metagenomic Analysis of Subtidal Sediments from Polar and Subpolar Coastal
Environments Highlights the Relevance of Anaerobic Hydrocarbon Degradation
Processes.
AB - In this work, we analyzed the community structure and metabolic potential of
sediment microbial communities in high-latitude coastal environments subjected to
low to moderate levels of chronic pollution. Subtidal sediments from four low
energy inlets located in polar and subpolar regions from both Hemispheres were
analyzed using large-scale 16S rRNA gene and metagenomic sequencing. Communities
showed high diversity (Shannon's index 6.8 to 10.2), with distinct phylogenetic
structures (<40% shared taxa at the Phylum level among regions) but similar
metabolic potential in terms of sequences assigned to KOs. Environmental factors
(mainly salinity, temperature, and in less extent organic pollution) were drivers
of both phylogenetic and functional traits. Bacterial taxa correlating with
hydrocarbon pollution included families of anaerobic or facultative anaerobic
lifestyle, such as Desulfuromonadaceae, Geobacteraceae, and Rhodocyclaceae. In
accordance, biomarker genes for anaerobic hydrocarbon degradation (bamA, ebdA,
bcrA, and bssA) were prevalent, only outnumbered by alkB, and their sequences
were taxonomically binned to the same bacterial groups. BssA-assigned metagenomic
sequences showed an extremely wide diversity distributed all along the phylogeny
known for this gene, including bssA sensu stricto, nmsA, assA, and other clusters
from poorly or not yet described variants. This work increases our understanding
of microbial community patterns in cold coastal sediments, and highlights the
relevance of anaerobic hydrocarbon degradation processes in subtidal
environments.
PMID- 28702707
TI - Host Specificity of Endophytic Mycobiota of Wild Nicotiana Plants from Arid
Regions of Northern Australia.
AB - In arid regions of northern Australia, plants survive under water deficit, high
temperatures, intense solar radiation and nutrient-impoverished soils. They
employ various morpho-physiological and biochemical adaptations including
interaction with microbial symbionts. We evaluated identity, host and tissue
association with geographical distribution of fungal endophytes isolated from
above- and below-ground tissues of plants of three indigenous Australian
Nicotiana species. Isolation frequency and alpha-diversity were significantly
higher for root endophyte assemblages than those of stem and leaf tissues. We
recorded no differences in endophyte species richness or diversity as a function
of sampling location, but did detect differences among different host genotypes
and plant tissues. There was a significant pattern of community similarity
associated with host genotypes but no consistent pattern of fungal community
structuring associated with sampling location and tissue type, regardless of the
community similarity measurements used.
PMID- 28702708
TI - Microbial Composition and Diversity Patterns in Deep Hyperthermal Aquifers from
the Western Plain of Romania.
AB - A limited number of studies have investigated the biodiversity in deep
continental hyperthermal aquifers and its influencing factors. Here, we present
the first description of microbial communities inhabiting the Pannonian and
Triassic hyperthermal aquifers from the Western Plain of Romania, the first one
being considered a deposit of "fossilized waters," while the latter is embedded
in the hydrological cycle due to natural refilling. The 11 investigated drillings
have an open interval between 952 and 3432 m below the surface, with collected
water temperatures ranging between 47 and 104 degrees C, these being the first
microbial communities characterized in deep continental water deposits with
outflow temperatures exceeding 80 degrees C. The abundances of bacterial 16S
rRNA genes varied from approximately 105-106 mL-1 in the Pannonian to about 102
104 mL-1 in the Triassic aquifer. A 16S rRNA gene metabarcoding analysis revealed
distinct microbial communities in the two water deposits, especially in the rare
taxa composition. The Pannonian aquifer was dominated by the bacterial genera
Hydrogenophilus and Thermodesulfobacterium, together with archaeal methanogens
from the Methanosaeta and Methanothermobacter groups. Firmicutes was prevalent in
the Triassic deposit with a large number of OTUs affiliated to
Thermoanaerobacteriaceae, Thermacetogenium, and Desulfotomaculum. Species
richness, evenness, and phylogenetic diversity increased alongside with the
abundance of mesophiles, their presence in the Triassic aquifer being most
probably caused by the refilling with large quantities of meteoric water in the
Carpathian Mountains. Altogether, our results show that the particular physico
cheminal characteristics of each aquifer, together with the water refilling
possibilities, seem to determine the microbial community structure.
PMID- 28702709
TI - The Unfolded Protein Response in the Immune Cell Development: Putting the
Caretaker in the Driving Seat.
AB - The endoplasmic reticulum (ER) is the primary site for the folding of proteins
destined for the membranous compartment and the extracellular space. This
elaborate function is coordinated by the unfolded protein response (UPR), a
stress-activated cellular program that governs proteostasis. In multicellular
organisms, cells have adopted specialized functions, which required functional
adaptations of the ER and its UPR. Recently, it has become clear that in immune
cells, the UPR has acquired functions that stretch far beyond its original scope.
In this review, we will discuss the role of the UPR in the immune system and
highlight the plasticity of this signaling cascade throughout immune cell
development .
PMID- 28702710
TI - Authentic IgM Fc Receptor (FcMUR).
AB - Since the bona fide Fc receptor for IgM antibody (FcuR) was identified eight
years ago, much progress has been made in defining its biochemical nature,
cellular distribution, and effector function. However, there are clearly
conflicting results, especially about the cellular distribution and function of
murine FcuR. In this short article, we will discuss recent findings from us and
other investigators along with our interpretations and comments that may help to
resolve the existing puzzles and should open new avenues of investigation.
PMID- 28702711
TI - A Simplified Method for Management of Platysmal Bands: Platysmotomy as an Office
Procedure.
AB - Restoration of the esthetic neck contour is an integral component of facial
rejuvenation. Characters of the aging neck include lipodystrophy, platysmal bands
and jowls that extend into the neck, reducing the esthetic characters of the
lower face. The authors present a new, simplified and economic method to manage
platysmal bands as an office procedure under local anesthesia using a standard 18
gauge syringe needle as a cutting tool. The new technique was used on a selected
group of female patients classified as non-surgical cases according to Rorich
classification. Twenty-five female patients shared in this study, with a follow
up period standardized to 1 year; one patient showed up after 1.5 years with
preserved esthetic outcome. One patient showed residual band managed by recutting
immediately after bruising and edema resolved. The technique was proven safe
regarding important neurovascular structures of the neck. Patients gave no
negative comments regarding results of surgery. Kappa statistical analysis showed
perfect interobserver agreement between patients and an independent assessor. The
authors concluded that the studied new technique is safe, effective, and valuable
for management of platysmal bands in a selected group of patients. Level of
Evidence IV This journal requires that authors assign a level of evidence to each
article. For a full description of these Evidence-Based Medicine ratings, please
refer to the Table of Contents or the online Instructions to Authors
www.springer.com/00266 .
PMID- 28702712
TI - Evaluation of the Anticonvulsant Effect of Brilliant Blue G, a Selective P2X7
Receptor Antagonist, in the iv PTZ-, Maximal Electroshock-, and 6 Hz-Induced
Seizure Tests in Mice.
AB - Epilepsy is one of the most common neurological disorders which is diagnosed in
around 65 million people worldwide. Clinically available antiepileptic drugs fail
to control epileptic activity in about 30% of patients and they are merely
symptomatic treatments and cannot cure or prevent epilepsy. There remains a need
for searching new therapeutic strategies for epileptic disorders. The P2X7
receptor has been recently investigated as a new target in epilepsy treatment.
Preclinical studies revealed that P2X7 receptor antagonists have anticonvulsant
properties in some models of epilepsy. We aimed to investigate whether P2X7
receptor antagonist-brilliant blue G (BBG)-is able to change seizure threshold in
three acute seizure models in mice, i.e., in the intravenous pentylenetetrazole
seizure threshold, maximal electroshock seizure threshold and 6 Hz psychomotor
seizure threshold tests. BBG was administered acutely (50-200 mg/kg, 30 min
before the tests) and sub-chronically (25-100 mg/kg, once daily for seven
consecutive days). Moreover, the chimney and grip strength tests were used to
estimate the influence of BBG on the motor coordination and muscular strength in
mice, respectively. Our results revealed only a week anticonvulsant potential of
the studied P2X7 receptor antagonist because it showed anticonvulsant action only
in the 6 Hz seizure test, both after acute and sub-chronic administration. BBG
did not significantly influence seizure thresholds in the remaining tests. Motor
coordination and muscular strength were not affected by the studied P2X7 receptor
antagonist. In summary, BBG does not possess any remarkable anticonvulsant
potential in acute seizure models in mice.
PMID- 28702713
TI - The Role of the Oligodendrocyte Lineage in Acute Brain Trauma.
AB - An acute brain injury is commonly characterized by an extended cellular damage.
The post-injury process of scar formation is largely determined by responses of
various local glial cells and blood-derived immune cells. The role of astrocytes
and microglia have been frequently reviewed in the traumatic sequelae. Here, we
summarize the diverse contributions of oligodendrocytes (OLs) and their precursor
cells (OPCs) in acute injuries. OLs at the lesion site are highly sensitive to a
damaging insult, provoked by Ca2+ overload after hyperexcitation originating from
increased levels of transmitters. At the lesion site, differentiating OPCs can
replace injured oligodendrocytes to guarantee proper myelination that is
instrumental for healthy brain function. In contrast to finally differentiated
and non-dividing OLs, OPCs are the most proliferative cells of the brain and
their proliferation rate even increases after injury. There exist even evidence
that OPCs might also generate some type of astrocyte beside OLs. Thereby, OPCs
can contribute to the generation and maintenance of the glial scar. In the
future, detailed knowledge of the molecular cues that help to prevent injury
evoked glial cell death and that control differentiation and myelination of the
oligodendroglial lineage will be pivotal in developing novel therapeutic
approaches.
PMID- 28702714
TI - Immunodeficiency in Two Female Patients with Incontinentia Pigmenti with
Heterozygous NEMO Mutation Diagnosed by LPS Unresponsiveness.
AB - PURPOSE: Anhidrotic ectodermal dysplasia with immunodeficiency (EDA-ID) is caused
by mutations in the NF-kappaB essential modulator (NEMO) or NF-kappaB inhibitor,
alpha (IKBA) genes. A heterozygous NEMO mutation causes incontinentia pigmenti
(IP) in females, while a hemizygous hypomorphic mutation of NEMO causes EDA-ID in
males. In general, immunodeficiency is not shown in IP patients. Here, we
investigated two female patients with IP and immunodeficiency. METHODS: The
patients were initially suspected to have IRAK4 deficiency and Mendelian
susceptibility to mycobacterial disease, respectively, because of recurrent
pneumonia with delayed umbilical cord detachment or disseminated mycobacterial
infectious disease. We measured tumor necrosis factor (TNF)-alpha production and
performed mutation screening. RESULTS: The TNF-alpha production from
lipopolysaccharide (LPS)-stimulated CD14-positive cells was partially defective
in both female patients. A genetic analysis showed them to carry the heterozygous
NEMO mutations c.1167_1168insC or c.1192C>T. Although NEMO mutations in IP
patients are typically eliminated by X-inactivation skewing, an analysis of cDNA
obtained from the somatic cells of the patients showed the persistence of these
mutations in peripheral blood mononuclear cells and peripheral granulocytes. A NF
kappaB reporter gene analysis using NEMO-deficient HEK293 cells showed the loss
of NF-kappaB activity in these NEMO mutants, while the NF-kappaB protein
expression levels by the NEMO mutants were consistent with those of wild-type
NEMO. CONCLUSIONS: The delayed skewing of the mutant allele may be responsible
for the observed innate immune defect in these patients. The detection of LPS
unresponsiveness is suitable for identifying female IP patients with
immunodeficiency.
PMID- 28702715
TI - [The EU Portal: Implementation, importance, and features].
AB - The European Medicines Agency (EMA) is developing a web-based EU portal with a
database "at Union level as a single entry point for the submission of data and
information relating to clinical trials in accordance with" the new EU regulation
No. 536/2014. The specifications are mostly published, but some documents are
still missing. Because the project is integrated and has dependencies on other
projects, this could result in other specification upgrades. The IT solution is
under ongoing development until project completion in quarter III of 2019. The EU
Portal and the database will be audited. If the audit is successful, the new
regulation will come into force in October 2018. The use of the EU Portal will
then be mandatory with some transition rules. The software development of the
portal is restricted to the regulation and the derived requirements. It is not
possible to implement any national requirements. We describe in this paper the
current key functionalities of the portal and try to derive requirements for a
national IT system.On 16.06.2017 the EMA Management Board announced that the
development of the new portal has been delayed and it is foreseen that the new
regulation can come into effect in 2019 at the earliest. The press release can be
found here:
http://www.ema.europa.eu/ema/index.jsp?curl=pages/news_and_events/news/2017/06/ne
s_detail_002764.jsp%26mid=WC0b01ac058004d5c1 (accessed: 12.07.2017).
PMID- 28702716
TI - Can the Pulmonary Artery Wedge Pressure be Used Reliably as a Surrogate for the
Left Atrial Mean Pressure in Pre-Fontan Evaluation?
AB - The correlation between mean pulmonary artery wedge pressure (PAWP) and left
atrial mean pressure (LAMP) has been poorly studied in patients with single
ventricle (SV) physiology (Bernstein et al. in Pediatr Cardiol 33: 15-20 2012).
The aim of this study is to determine if the PAWP can be used safely as a
surrogate to the LAMP to calculate the pulmonary vascular resistance (PVR) during
the pre-Fontan evaluation. Also, we aimed to understand if the presence of
significant systemic-to-pulmonary collaterals (SPCs) is a confounding factor for
accurate estimation of the LAMP. From February 2007 to February 2017, forty-one
patients were eligible for inclusion in the study. These patients were varied in
terms of underlying cardiac malformation. Sex distribution was equal with 20
males and 21 females. Median weight was 11.8 kg, median body surface area was
0.51 m2, median age at catheterization was 2 years, and the median age at Glenn
surgery was 5 months. We found the left and right PAWP and LAMP correlated
strongly and the differences in the measurements were negligible. Similar
findings were observed when calculating PVRs using PAWP and LAMP. These findings
were more pronounced in the absence of significant SPCs. PAWP and LAMP
correlation was still valid in the presence of significant SPCs; however, the
correlation among the calculated PVRs was more attenuated.
PMID- 28702717
TI - Mindfulness-Based Stress Reduction and Group Support Decrease Stress in
Adolescents with Cardiac Diagnoses: A Randomized Two-Group Study.
AB - Adolescents with cardiac diagnoses face unique challenges that can cause
psychosocial distress. This study compares a Mindfulness-Based Stress Reduction
(MBSR) program to a video online support group for adolescents with cardiac
diagnoses. MBSR is a structured psycho-educational program which includes yoga,
meditation, cognitive restructuring, and group support. A published feasibility
study by our group showed significant reduction in anxiety following this
intervention. Participants were randomized to MBSR or video online support group,
and completed measures of anxiety, depression, illness-related stress, and coping
pre- and post-6-session interventions. Qualitative data were obtained from post
intervention interviews. A total of 46 teens participated (mean 14.8 years; 63%
female). Participants had congenital heart disease and/or cardiac device (52%),
or postural orthostatic tachycardia syndrome (48%). Illness-related stress
significantly decreased in both groups. Greater use of coping skills predicted
lower levels of depression in both groups post-study completion. Higher baseline
anxiety/depression scores predicted improved anxiety/depression scores in both
groups. Each group reported the benefits of social support. The MBSR group
further expressed benefits of learning specific techniques, strategies, and
skills that they applied in real-life situations to relieve distress. Both the
MBSR intervention and video support group were effective in reducing distress in
this sample. Qualitative data elucidated the added benefits of using MBSR
techniques to manage stress and symptoms. The video group format is useful for
teens that cannot meet in person but can benefit from group support. Psychosocial
interventions with stress management techniques and/or group support can reduce
distress in adolescents with cardiac diagnoses.
PMID- 28702718
TI - Single-Center Experience Using Selexipag in a Pediatric Population.
AB - Pulmonary arterial hypertension (PAH) is a rare and progressive disorder. Current
treatment in the pediatric population includes phosphodiesterase 5 inhibitors
(PDE-5i), endothelin receptor antagonists (ERA), and both inhaled and intravenous
prostacyclin pathway agonists. As of December 22, 2015 the first oral
prostacyclin pathway agonist, selexipag (Uptravi(r)), was FDA approved in the US.
In this case series, we discuss our single-center experience using selexipag in a
pediatric population, composed of both patients with idiopathic PAH, and patients
with congenital heart disease and PAH.
PMID- 28702719
TI - Dietary iron intake and availability are related to maternal education level in
overweight/obese adolescents.
AB - PURPOSE: To compare intakes of dietary iron and enhancers and inhibitors of iron
absorption between overweight/obese (OW/OB) adolescents and their normal weight
(NW) peers, and between parental education levels stratified by weight status.
METHODS: This was a comparative cross-sectional study of adolescents (n 121 OW/OB
and n 102 NW) aged 12-14 years, attending a secondary school in Nonthaburi
province, Thailand. Socio-demographic data were obtained from participants'
parents using a questionnaire. Participants recorded their intakes for 3 non
consecutive days, using a prospective food record. RESULTS: Compared with NW
adolescents, OW/OB adolescents consumed more total protein and animal protein
after adjustment for energy intake (both p = 0.047). OW/OB adolescents whose
mothers were less educated consumed more total iron and available iron after
adjustment for energy intake, compared with their OW/OB peers whose mothers were
more educated (p = 0.045 and p = 0.040). NW adolescents with more highly educated
mothers had higher absolute and energy-adjusted fibre intakes (both p = 0.047).
However, NW adolescents of mothers with a high-intermediate level of education
consumed less calcium, after adjustment for energy intake (p = 0.028).
CONCLUSIONS: OW/OB adolescents with less educated mothers had higher energy
adjusted intakes of iron and available iron. Dietary differences in OW/OB
adolescents relative to maternal education, and other socioeconomic indicators,
should be explored in a nationally representative data set.
PMID- 28702720
TI - Soft drinks consumption is associated with nonalcoholic fatty liver disease
independent of metabolic syndrome in Chinese population.
AB - PURPOSE: Excessive consumption of soft drinks is associated with nonalcoholic
fatty liver disease (NAFLD). However, the association between soft drinks
consumption and NAFLD is unclear in non-Caucasian adults with relatively low soft
drinks consumption. The aim of this study was to assess the association between
soft drinks consumption and NAFLD in Chinese adults. METHODS: A cross-sectional
study was conducted with 26,790 adults living in Tianjin, China. NAFLD (with
elevated alanine aminotransferase [ALT]) was diagnosed by the liver
ultrasonography and serum ALT concentrations. Soft drinks consumption was
assessed using a validated self-administered food frequency questionnaire, and it
was summarized as three categories for analysis: almost never (reference), <1
cup/week, and >=1 cups/week. Metabolic syndrome (MetS) was defined according to
the criteria of the American Heart Association scientific statements of 2009. The
association between soft drinks consumption and NAFLD was assessed by multiple
logistic regression analysis. RESULTS: The prevalence of NAFLD and NAFLD with
elevated ALT was 27.1 and 6.5%, respectively. After adjustment for potential
confounding variables (including MetS), the odds ratios (95% confidence
intervals) for NAFLD or NAFLD with elevated ALT across soft drinks consumption
were 1.00 (reference) for almost never, 1.14 (1.02-1.27) or 1.16 (0.98-1.37) for
<1 cup/week, and 1.26 (1.14-1.40) or 1.32 (1.13-1.53) for >=1 cups/week (both P
for trend <0.001), respectively. CONCLUSIONS: This is the first study to
demonstrate that soft drinks consumption is associated with NAFLD independent of
MetS in Chinese adults with relatively low soft drinks consumption. These results
suggest that reducing soft drinks consumption might be beneficial to the
prevention of NAFLD.
PMID- 28702721
TI - Peptides semax and selank affect the behavior of rats with 6-OHDA induced PD-like
parkinsonism.
AB - Parkinson's disease (PD) is the second most common severe neurodegenerative
disorder that is characterized by progressive degeneration of dopaminergic
neurons (DA neurons) in the substantia nigra pars compacta (SNpc) region of the
brain. In the present study, we investigated the effects of the synthetic
regulatory peptides Semax (analog of an ACTH 4-10 fragment (ACTH4-10)) and Selank
(analog of immunomodulatory taftsin) on behavior of rats with 6-hydroxidopamine
(6-OHDA) induced PD-like parkinsonism. It was showed that both peptides did not
affect motor activity of rats in elevated cross shaped maze and passive defensive
behavior of the animals. At the same time, Selank decreased level of anxiety of
rats with toxic damage of DA neurons in elevated cross shaped maze. Previously
such effects of Selank were revealed in healthy rodents (rats and mice) with
different models of psycho-emotional stress. Therefore, toxic damage of
substantia nigra does not affect the response of the rat organism on this
peptide.
PMID- 28702722
TI - Microbial processes in the Kanda Bay, a meromictic water body artifically
separated from the White Sea.
AB - Sings of meromixis are found by means of microbiological and biogeochemical
investigations in the southernn part of the Kanda Bay, an artificial water body
separated front the White Sea with a railway dam. The concentration of oxygen in
the bottom layer attained 1.9 mmol/L, intensity of the process of microbial
sulfate reduction, 3.0 MUmol of sulfur/(L day). The concentration of dissolved
methane, 3.7 MUmol/L. Isotopic composition of carbon in methane (delta13C (CH4) =
79.20/00) indicates to its microbial genesis. At present, Kanda Bay is a sole in
Russia man-made marine water body for which there are data on the rate of
microbial processes responsible for formation of bottom water layer containing
hydrogen sulfide and methane.
PMID- 28702723
TI - Quantitative characteristics of the littoral fauna of Gronfjorden Gulf
(Spitsbergen) during winter and spring of 2016.
AB - The first description of the quantitative and qualitative compositions of the
littoral fauna of Gronfjorden Gulf during the winter and spring period is given.
Granulometric analysis of the surface sediments of the littoral has been
performed. Thirty invertebrate taxa that did not leave the littoral zone during
wintertime and could survive complete freezing during ebb have been identified.
Species diversity and population density of the invertebrates were shown to
depend on the granulometric size composition of the surface sediments.
PMID- 28702724
TI - Acoustic structure of alarm calls in Indian sambar (Rusa unicolor) and Indian
muntjac (Muntiacus vaginalis) in South Vietnam.
AB - The alarm call acoustic structure and nonlinear vocal phenomena of the Indian
sambar (Rusa unicolor) and northern Indian muntjac (Muntiacus vaginalis) have
been analyzed in detail as well as their vocal behavior in response to mobbing
humans under natural conditions of southern Vietnam. The alarm calls of sambars,
tonal barks separated by large intervals, were produced by animals standing on
the place and gazing at a potentially dangerous object. Muntjacs flee off in
danger and produced a series of dull barks interrupted with short intervals from
a distance. The alarm call frequencies were characterized for sambars and
muntjacs. The results of our study have been compared with the published data on
alarm calls of other Cervidae species.
PMID- 28702725
TI - Unexpectedly high genetic diversity of the asiatic short-tailed shrews Blarinella
(Mammalia, Lipotyphla, Soricidae).
AB - Genetic diversity of the genus Blarinella was studied using one mitochondrial and
four nuclear genes as examples. The first genotyping of shrews from the southeast
of Gansu province (China), which is a typical habitat of B. griselda, has been
performed. Molecular genetic analysis showed that Blarinella sp. from southern
Gansu stand apart among the other representatives of the genus and can be
assigned to neither of the known species.
PMID- 28702726
TI - Distinct features of intraspecific and intrapopulation variability of the skull
size in the red fox.
AB - The range of chronographic variability of the average size of the skull in the
red fox (data collected by the authors) from a compact area in the Middle Urals
has been assessed for a 30-year period, and the results obtained have been
compared with the published data on the geographical variability within the vast
species range. The range of changes of the average dimensions of the skull over
time spanned almost the entire range of geographical variability. Therefore, the
problem of search for factors that determine the morphological diversity arises.
PMID- 28702727
TI - Electric discharges and electrogenesis peculiarity in two African upside-down
catfishes, Synodontis caudovittatus and S. eupterus (Mochokidae, Siluriformes).
AB - The paper reports spontaneous generation of weak electric discharges with an
amplitude of 0.4-1.0 mV and a frequency of 3-9 min-1 by solitary Synodontis
caudovittatus fish. When fish individuals were tested in pairs, their aggressive
defense interactions were associated with an increase in the amplitude of the
discharges (up to 30-45 mV) compared to the discharges of individual fish, while
the duration of the pulses increased up to 20-25 ms due to the prolongation of
the second phase. In S. eupterus, electric activity was recorded only in the
course of aggression-defense interactions, while spontaneous generation of
discharges was not observed at all. The paper discusses the different aspects of
electrocummunication between the catfish including the role of the reversion of
polarity of the merged summated discharges with increased duration.
PMID- 28702728
TI - CD8+ T cell expansion in HIV/HCV coinfection is associated with systemic
inflammation.
AB - High prevalence of non-AIDS-defining illnesses in treated HIV-infected patients
is associated with increased peripheral CD8+ T cell counts. Hepatitis C virus
(HCV) coinfection is an additional risk factor for the development of non-AIDS
events. We found that, in HIV/HCV coinfection, the increased proportion of CD8+ T
lymphocytes is due to the effector memory and terminal effector T cells gain.
Moreover, in these patients, the accumulation of highly differentiated forms of
CD8+ T lymphocytes was associated with increased concentrations of inflammatory
indices.
PMID- 28702729
TI - Improvement of the night sleep quality by electrocutaneous subthreshold
stimulation synchronized with the slow wave sleep.
AB - Changes in sleep characteristics were studied under the non-wake-up stimulation
with current pulses of less than 1 MUA on average, applied to the palmar surface
skin receptors during Delta-sleep. A significant increase in duration of the
first and second cycles of deep sleep has been found, as well as a shorter latent
period before the Delta-sleep onset and a longer time of the rapid sleep (REM
phase). The sleep structure improvement was accompanied by the reduced reactive
anxiety and depression and an increase in subjective physical efficiency.
PMID- 28702730
TI - Compressive nonlinearity of human hearing in sound spectra discrimination.
AB - In the psychophysical experiments reported here, cochlear compression function
was derived by comparing on-frequency and off-frequency masking. The signal was
rippled spectrum noise. The ripple density discrimination threshold was measured
in the ripple phase reversion test. An increase in masker intensity led to a
decrease in a resolvable ripple density threshold. The on-frequency masker level
at threshold increased proportionally to the signal intensity. The off-frequency
masker level at threshold also increased proportionally to the signal at signal
intensity levels below 50 dB, whereas at signal levels above 60 dB SPL, the ratio
of the masker level at threshold gradient to signal level gradient was 1 : 5
dB/dB, revealing cochlear compression.
PMID- 28702731
TI - Chronic cold stress modulates the function of peritoneal macrophages in vivo.
AB - On day 7 of chronic cold stress, concentration of corticosterone in plasma was
established to increase, zymosan-induced production of reactive oxygen species
was activated, and IL-10 synthesis by macrophages was enhanced regardless of the
opiate receptor blockade. Increase in the concentration of corticosterone was
independent of the blockade of opioid receptors, whereas the zymosan-induced
increase in the production of oxygen radicals and activation of the spontaneous
production of IL-10 was blocked in mice by naloxone. Chronic cold stress had no
effect on the production of IL-1beta and TNF-alpha.
PMID- 28702732
TI - Distribution of populations of ringed seal Phoca hispida and bearded seal
Erignathus barbatus in shallow and average-deep areas of the southwestern part of
the Kara Sea in summer 2015.
AB - In August-September 2015 in the southwest part of the Kara Sea, visual censuses
of ringed seal (Phoca hispida) and bearded seal (Erignatus barbatus) from
research vessels were carried out in the water area of 49 814 km2. For the first
time, for calculation of abundance and density on ice-free area the SEAL
CALCULATION (TYULEN-RASCHET) software was used with application of separate
extrapolation method by the selected sectors. Calculation for the whole census
polygon yielded abundance of ringed seal of 4163 +/- 16.9% and abundance of
bearded seal of 1026 +/- 28.4%. On the basis of the census results, a preliminary
estimation of distribution of pinnipeds by various depths is presented.
PMID- 28702733
TI - Isotope and microelement systematics of Gallionella sp.-containing bacterial mats
from the northwest of the East European Platform.
AB - Microelement composition of Gallionella sp.-containing bacterial mats from the
environs of St. Petersburg and isotope composition of organic carbon, strontium,
and neodymium from these mats have been determined. Isotope and microelement
systematics of iron oxides of bacterial origin characterize the geochemistry of
aquafacies that contain ferrobacteria. Certain pre-Cambrian ferruginous
quartzites have a similar composition; therefore, one may assume that bacterial
oxidation of iron under continental conditions had occurred upon the formation of
ironstone during the Precambrian.
PMID- 28702734
TI - Understanding disease and illness.
PMID- 28702736
TI - Changes in the axon terminals of primary afferents from a single vibrissa in the
rat trigeminal nuclei after active touch deprivation or exposure to an enriched
environment.
AB - Lasting modifications of sensory input induce structural and functional changes
in the brain, but the involvement of primary sensory neurons in this plasticity
has been practically ignored. Here, we examine qualitatively and quantitatively
the central axonal terminations of a population of trigeminal ganglion neurons,
whose peripheral axons innervate a single mystacial vibrissa. Vibrissa follicles
are heavily innervated by myelinated and unmyelinated fibers that exit the
follicle mainly through a single deep vibrissal nerve. We made intraneural
injections of a mixture of cholera-toxin B (CTB) and isolectin B4, tracers for
myelinated and unmyelinated fibers, respectively, in three groups of young adult
rats: controls, animals subjected to chronic haptic touch deprivation by
unilateral whisker trimming, and rats exposed for 2 months to environmental
enrichment. The regional and laminar pattern of terminal arborizations in the
trigeminal nuclei of the brain stem did not show gross changes after sensory
input modification. However, there were significant and widespread increases in
the number and size of CTB-labeled varicosities in the enriched condition, and a
prominent expansion in both parameters in laminae III-IV of the caudal division
of the spinal nucleus in the whisker trimming condition. No obvious changes were
detected in IB4-labeled terminals in laminae I-II. These results show that a
prolonged exposure to changes in sensory input without any neural damage is
capable of inducing structural changes in terminals of primary afferents in
mature animals, and highlight the importance of peripheral structures as the
presumed earliest players in sensory experience-dependent plasticity.
PMID- 28702735
TI - Is the extrastriate body area part of the dorsal visuomotor stream?
AB - The extrastriate body area (EBA) processes visual information about body parts,
and it is considered one among a series of category-specific perceptual modules
distributed across the occipito-temporal cortex. However, recent evidence raises
the possibility that EBA might also provide an interface between perception and
action, linking the ventral and dorsal streams of visual information processing.
Here, we assess anatomical evidence supporting this possibility. We localise EBA
in individual subjects using a perceptual task and compare the characteristics of
its functional and structural connectivity to those of two perceptual areas, the
lateral occipital complex (LOC) and the fusiform body area (FBA), separately for
each hemisphere. We apply complementary analyses of resting-state fMRI and
diffusion-weighted MRI data in a group of healthy right-handed human subjects (N
= 31). Functional and structural connectivity profiles indicate that EBA
interacts more strongly with dorsal-stream regions compared to other portions of
the occipito-temporal cortex involved in processing body parts (FBA) and object
identification (LOC). These findings provide anatomical ground for a revision of
the functional role of EBA. Building on a number of recent observations, we
suggest that EBA contributes to planning goal-directed actions, possibly by
specifying a desired postural configuration to parieto-frontal areas involved in
computing movement parameters.
PMID- 28702737
TI - The Relationship of Anxiety and Depression to Subjective Well-Being in a Mainland
Chinese Sample.
AB - This pilot study examines anxiety, depression, and well-being in a mainland
Chinese sample and discusses the implications for mental health care. The
Hospital Anxiety and Depression Scale, Functional Assessment of Chronic Illness
Therapy-Spiritual Well-being, and the Body Mind Spirit Well-Being Inventory were
administered to 60 mainland China residents. Correlational analyses revealed
significant relationships among depression, anxiety, and every domain of well
being except the faith domain. Levels of depression and anxiety are inversely
related to levels of well-being in a mainland Chinese sample. Chinese culture was
expected to moderate this relationship; however, this was not confirmed by the
results.
PMID- 28702739
TI - Value of the neutrophil-to-lymphocyte ratio in predicting left ventricular
recovery in patients with peripartum cardiomyopathy.
AB - OBJECTIVE: The aim of this study was to assess the value of the neutrophil-to
lymphocyte ratio (NLR) in predicting left ventricular (LV) recovery in patients
with peripartum cardiomyopathy (PPCM). METHODS: Patients with PPCM (n = 40), who
were admitted to our tertiary reference hospital between 2007 and 2015 were
retrospectively analyzed. All patients were followed-up for at least 12 months
after the diagnosis. All patients had standard echocardiographic examination at
baseline and the last follow-up visit. Recovery of LV function was defined as the
presence of LV ejection fraction (EF) >45%. Data on blood parameters were also
collected at baseline. Univariate and multivariate analysis were used to assess
the significant predictive variables for persistent LV systolic dysfunction.
RESULTS: Of the patients 21 (52.5%) did not recover LV function at the last
follow-up visit (nonrecovery group), while 19 of the patients (47.5%) exhibited
LV recovery (recovery group). The LV EF and fractional shortening (FS) were
significantly lower in the nonrecovery group. The baseline LV end-diastolic
diameter, LV end-systolic diameter (LVESD) and systolic pulmonary arterial
pressure were significantly increased in the nonrecovery group. The NLR, C
reactive protein and troponin levels were significantly higher in the nonrecovery
group. In multivariate logistic regression analysis only NLR and LVESD were
identified as independent predictors of persistent LV systolic dysfunction in
patients with PPCM (p = 0.020 and p = 0.009 respectively). CONCLUSION: Elevated
NLR and increased LVESD were independent prognostic factors in predicting
persistent LV dysfunction in patients with PPCM. The NLR might assist in
identifying high risk patients with PPCM.
PMID- 28702738
TI - Impact of etiological treatment on prognosis.
AB - Portal hypertension (PHT) is a frequent and severe complication of cirrhosis. PHT
may lead to the development of various complications with high mortality. Liver
transplantation is the gold standard as a surgical curative treatment for end
stage liver disease. Theoretically, etiological treatment focusing on the
pathophysiology of the underlying disease should be the objective of the
nonsurgical management of cirrhotic PHT. Chronic viral hepatitis is the major
etiology of cirrhosis and PHT. In cirrhotic patients with chronic hepatitis B
virus infection, antiviral therapies can suppress viral replication, ameliorate
hepatic inflammation, regress fibrosis, and restore liver functional reserve.
Moreover, they can delay the progression of liver cirrhosis and ameliorate the
severity of PHT. In patients with hepatitis C virus-induced liver cirrhosis,
interferon and ribavirin combination therapy provide a favorable long-term
prognosis, including lower rates of liver-related and non-liver-related deaths,
hepatic decompensation, and hepatocellular carcinoma, particularly in those who
have successful eradication of the virus after therapy. In patients with PHT,
direct antivirals (DAAs) for hepatitis C virus infection have good safety
profiles and excellent viral suppression. Moreover, DAAs can reduce hepatic
venous pressure gradient. However, these effects are stronger during the earlier
stage of liver cirrhosis. Abstinence is the cornerstone of etiological treatment
for alcoholic liver disease. The effects of pharmacological treatments are not
satisfactory, and additional studies are mandatory.
PMID- 28702740
TI - Large Bariatric-Specific Stents and Over-the-Scope Clips in the Management of
Post-Bariatric Surgery Leaks.
AB - BACKGROUND: Endoscopic stents are successful in the management of surgical leaks;
however, stent migration remains a significant problem. In this study, we present
our approach depending on a large bariatrics-specific stent (Mega stent) and over
the-scope clips in the management of post-bariatric surgery leaks. METHODS: A
retrospective analysis of all patients with post-bariatric surgery leaks treated
at our institution using an approach reliant on Mega stents and over-the-scope
clips was conducted. Potential factors associated with procedure success and
occurrence of complications were also evaluated. RESULTS: A total of 81 stents
were inserted in 62 patients with post-bariatric surgery leaks, 46 sleeve
gastrectomies (73%) and 16 Roux-en-Y gastric bypass (27%). Over-the-scope clips
were applied in 29 patients (46%). Leak closure was achieved in 51 patients
(82%). Median number of procedures per patient was 3 (range 2-8). Complications
included the following: stent migration (11/62, 18%), intolerance necessitating
premature removal (7/62, 11%), esophageal stricture (8/62, 13%), bleeding (4/62,
6%), perforation (4/62, 6%). One stent-induced mortality was encountered
(bleeding). The presence of open surgery (vs laparoscopic) was significantly
associated with the occurrence of stent-induced complications (p 0.002).
CONCLUSION: The approach combining Mega stents and over-the-scope clips is highly
effective in the management of post-bariatric surgery leaks and is associated
with a low rate of stent migration and a low number of procedures and stents per
patient. Mega stents, however, should be used with great caution due to the
significant morbidity associated with their use.
PMID- 28702742
TI - Abscisic acid negatively regulates post-penetration resistance of Arabidopsis to
the biotrophic powdery mildew fungus.
AB - Pytohormone abscisic acid (ABA) plays important roles in defense responses.
Nonetheless, how ABA regulates plant resistance to biotrophic fungi remains
largely unknown. Arabidopsis ABA-deficient mutants, aba2-1 and aba3-1, displayed
enhanced resistance to the biotrophic powdery mildew fungus Golovinomyces
cichoracearum. Moreover, exogenously administered ABA increased the
susceptibility of Arabidopsis to G. cichoracearum. Arabidopsis ABA perception
components mutants, abi1-1 and abi2-1, also displayed similar phenotypes to ABA
deficient mutants in resistance to G. cichoracearum. However, the resistance to
G. cichoracearum is not changed in downstream ABA signaling transduction mutants,
abi3-1, abi4-1, and abi5-1. Microscopic examination revealed that hyphal growth
and conidiophore production of G. cichoracearum were compromised in the ABA
deficient mutants, even though pre-penetration and penetration growth of the
fungus were not affected. In addition, salicylic acid (SA) and MPK3 are found to
be involved in ABA-regulated resistance to G. cichoracearum. Our work
demonstrates that ABA negatively regulates post-penetration resistance of
Arabidopsis to powdery mildew fungus G. cichoracearum, probably through
antagonizing the function of SA.
PMID- 28702741
TI - Massive Weight Loss Obtained by Bariatric Surgery Affects Semen Quality in Morbid
Male Obesity: a Preliminary Prospective Double-Armed Study.
AB - OBJECTIVES: The aim of this study is to evaluate the effect of massive weight
loss on the seminal parameters at 6 months from bariatric surgery. DESIGN: Two
armed prospective study performed in 31 morbidly obese men, undergoing
laparoscopic roux-en-Y-gastric bypass (n = 23) or non-operated (n = 8), assessing
sex hormones, conventional (sperm motility, morphology, number, semen volume),
and non-conventional (DNA fragmentation and seminal interleukin-8), semen
parameters, at baseline and after 6 months from surgery or patients' recruitment.
RESULTS: In operated patients only, a statistically significant improvement in
the sex hormones was confirmed. Similarly, a positive trend in the
progressive/total sperm motility and number was observed, though only the
increase in semen volume and viability was statistically significant (Delta = 0.6
ml and 10%, P < 0.05, respectively). A decrease in the seminal interleukin-8
levels and in the sperm DNA fragmentation was also present after bariatric
surgery, whereas these parameters even increased in non-operated subjects. Age
adjusted multivariate analysis showed that the BMI variations significantly
correlated with the changes in the sperm morphology (beta = -0.675, P = 0.025),
sperm number (beta = 0.891, P = 0.000), and semen volume (r = 0.618, P = 0.015).
CONCLUSION: The massive weight loss obtained with bariatric surgery was
associated with an improvement in some semen parameters. The correlations found
between weight loss and semen parameter variations after surgery suggest that
these might occur early downstream of the testis and more slowly than the changes
in the sex hormones.
PMID- 28702743
TI - Radiological findings of transorbital penetrating intracranial injury in a child.
AB - In penetrating injuries, woods are known to be difficult to detect with
radiological imaging studies, because the wood density are known to be extremely
close to the value of air on CT. Adjustment of CT window and reconstruction of a
3D image from CT images allowed us to more accurately distinguish wood from air
and to find the fragment of the wooden chopstick. It is particularly useful in
transorbital penetrating injury.
PMID- 28702745
TI - Quercetin Reverses Altered Energy Metabolism in the Heart of Rats Receiving
Adriamycin Chemotherapy.
AB - The primary aim of this study was to find the potential modulatory roles of
quercetin (QUE) against Adriamycin (ADR)-induced cardiotoxicity. A total of 50
rats were assigned to five groups: a control group, an ADR-treated group, a QUE
treated group, a prophylaxis-cotreated group, and a therapeutic-cotreated group,
respectively. QUE exhibited a significant cardioprotective effect, particularly,
when it was administered prior to and concurrently with ADR treatment
(prophylaxis-cotreated group). This effect was biochemically evident by the
significant decreases in the serum levels of myocardial injury biomarkers such as
troponin, creatine kinase-myocardium bound, and creatine phosphokinase. In
addition, significant elevations in myocardial antioxidant indices coupled with
significant reductions in myocardial malondialdehyde contents and DNA damage,
elicited by ADR injection, were observed. All these biochemical improvements were
accompanied by a significant histopathological recovery and obvious modulation of
the AMP-activated protein kinase (AMPK) signaling pathway by promoting the
expression of the AMPKalpha2, PPARalpha, and PCG-1alpha genes. Taken together,
these findings conclusively showed that QUE administration through its
antioxidant capacity and myocardial energy metabolism restoration provides a
prophylactic effect in response to ADR-induced deleterious effects, in the rat
heart.
PMID- 28702744
TI - Plant extracts and natural compounds used against UVB-induced photoaging.
AB - Skin is continuously exposed to a variety of environmental stresses, including
ultraviolet (UV) radiation. UVB is an inherent component of sunlight that crosses
the epidermis and reaches the upper dermis, leading to increased oxidative
stress, activation of inflammatory response and accumulation of DNA damage among
other effects. The increase in UVB radiation on earth due to the destruction of
stratospheric ozone poses a major environmental threat to the skin, increasing
the risk of damage with long-term consequences, such as photoaging and
photocarcinogenesis. Extracts from plants and natural compounds have been
historically used in traditional medicine in the form of teas and ointments but
the effect of most of these compounds has yet to be verified. Regarding the
increasing concern of the population with issues related to quality of life and
appearance, the cosmetic market for anti-aging and photoprotective products based
on natural compounds is continuously growing, and there is increasing requirement
of expansion on research in this field. In this review we summarized the most
current and relevant information concerning plant extracts and natural compounds
that are able to protect or mitigate the deleterious effects caused by photoaging
in different experimental models.
PMID- 28702746
TI - CORR Insights(r): Periprosthetic Joint Infection Is the Main Cause of Failure for
Modern Knee Arthroplasty: An Analysis of 11,134 Knees.
PMID- 28702747
TI - Management of Supine Hypertension Complicating Neurogenic Orthostatic
Hypotension.
AB - Neurogenic orthostatic hypotension (NOH) can be present in a number of disorders,
including synucleinopathies, autoimmune disorders, and various genetic disorders.
All are characterized by defective norepinephrine release from sympathetic
terminals upon standing, resulting in impaired vasoconstriction. NOH is defined
as a drop in systolic blood pressure >=20 mmHg or diastolic blood pressure >=10
mmHg, or both, within 3 minutes of standing or head up-tilt at a minimum of 60
degrees . However, approximately 50% of patients have associated supine
hypertension, which greatly complicates treatment. Supine hypertension not only
is a common side effect of many anti-hypotensive agents but is also present in
untreated patients, suggesting it is, in part, innate to the pathophysiology of
autonomic dysfunction. Pathological mechanisms differ depending on the underlying
autonomic disorder. In central neurodegenerative disorders, residual post
ganglionic sympathetic activity is likely the primary mechanism, whereas plasma
angiotensin, aldosterone, and inappropriate mineralocorticoid receptor activity
may contribute in peripheral autonomic lesions. Baroreflex failure/loss of
baroreflex buffering is common to both. More work is required. Clinically, there
is much dispute regarding the treatment of supine hypertension when there is a
risk of exacerbating orthostatic hypotension. However, given the similar levels
of end-organ damage (i.e., heart attack and stroke) seen with transient
hypertension, it seems clear that treatment is important. Current therapies for
both NOH and supine hypertension include a combination of pharmacological and
conservative measures. However, in addition to the current standard of care,
protocols may consider 24-h blood pressure monitoring and potential future
examination of the peripheral post-ganglionic sympathetic nerves in order to
apply individualized adjunct therapies. Finally, no anti-hypertensive agents are
currently approved for use in this patient population, and development of novel
therapies should focus on short-acting agents, selective to the supine position,
that act primarily at night when hypertension is most severe/prolonged.
PMID- 28702748
TI - [Splice variant AR-V7 : Is it time for its routine use as a predictive marker in
prostate cancer?]
AB - Androgen receptor splice variants (AR-Vs), if overexpressed, lack the ligand
binding domain conveying metastasized castration-resistant prostate cancer with a
therapeutic resistance to androgen receptor signaling inhibitors. Particularly AR
V7 has recently been proposed as a potential predictive biomarker to identify
patients who would probably benefit most from taxane-based cytotoxic treatment.
Several assays to substantiate or quantify AR-V7 expression have recently been
proposed. However, their broad clinical value is still debatable. This
contemporary update aims to shed light on the current evidence in the field and
draw distinct practical conclusions.
PMID- 28702749
TI - Evaluation of different surgical methods in treating recurrent patella
dislocation after three-dimensional reconstruction.
AB - PURPOSE: Recurrent patella dislocation (RPD) is the most common complication of
patellar instability. The effects of different surgical techniques on the outcome
of RPD treatments remain unclear. This study was conducted to compare the effects
of three surgical techniques in treating RPD by three-dimensional (3D)
reconstruction from computed tomography (CT) scans. METHODS: Sixty-eight patients
with RPD and no previous surgical treatments who attended our hospital between
October 2010 and 2013 were enrolled and randomly assigned into three groups: (1)
medial patellofemoral ligament (MPFL) reconstruction and medial patellar
retinaculum (MPR) plication group; (2) lateral patellar retinaculum (LPR) release
and MPR plication group; and (3) MPFL reconstruction and LPR release group. Knee
joints with flexion of 20 degrees were scanned by a 64-row CT scanner and 3D
reconstructed. Congruence angle (CA), patellar tilt angle (PTA), lateral
patellofemoral angle (LPFA), and congruence of the lateral patellofemoral
articular surface were measured. Knee joint function was evaluated by the Lysholm
knee scoring scale, Kujala patellofemoral score, and International Knee
Documentation Committee (IKDC) score. RESULTS: Pre-operative clinical
characteristics were similar across groups. After treatment, the CA, PTA, and
LPFA were reverted to normal post-operatively without statistically significant
between-group differences. The MPFL reconstruction and LPR release group had the
highest congruence of the lateral patellofemoral articular surface; while the
(LPR) release and (MPR) plication group had the lowest Lysholm knee scoring
scale, Kujala patellofemoral score, and IKDC score after surgery. CONCLUSIONS:
The MPFL reconstruction and LPR release group had the best clinical outcomes
among the three surgical methods, as indicated by better joint congruence after
3D joint reconstruction and higher knee function scores.
PMID- 28702750
TI - Function and activity after minimally invasive total hip arthroplasty compared to
a healthy population.
AB - PURPOSE: The aim of the present study was to compare the daily activity and
functionality in a patient cohort 12 months after total hip arthroplasty (THA)
using a direct anterior approach with a healthy non-operated control population.
METHODS: Sixty-four patients who underwent THA and 59 healthy individuals
(control) were assessed regarding their daily activity and joint functionality
utilizing the Harris hip score (HHS), the extra short musculoskeletal functional
assessment questionnaire (XSFMA), the Short Form 36 (SF-36) health survey and a
StepwatchTM Activity Monitor (SAM). Post-operative x-ray images after THA were
analysed regarding inclination and stem positioning. RESULTS: Twelve months after
surgery, the average HHS showed no significant difference between both groups
equalling 90.7 points in the THA patient group and 90.8 in the healthy volunteer
group. The XSFMA functional index scores were 11.0 (THA) and 5.0 (control) while
the bother index summed up to a score of 15.3 (THA) and 7.6 (control)
respectively thus differing significantly (p < 0.001). Daily activity equalled
4227 (THA) and 4687 (control) load cycles per day (p = 0.327) while a number of
5658 (THA) and 6417 (control) steps per day (p = 0.011) was recorded. The SF-36
physical component scores were 47.3 (THA) and 50.6 (control) points while the
psychometric properties added up to a score of 56.1 (THA) and 55.9 (control). The
physical component was determined to be significantly different (p < 0.001)
whereas no statistically significant difference could be shown for the
psychometric properties (p = 0.511). The radiographic analysis revealed an
average cup inclination of 39.9 degrees without signs of migration. Stem
positioning was neutral in 53% of all cases while 36% were graded varus and 11%
valgus. CONCLUSION: In summary, our short-term results show an activity,
functionality and quality of life for patients one year after THA comparable to
healthy control individuals.
PMID- 28702751
TI - Complexes of gastrin with In3+, Ru3+ or Ga3+ ions are not recognised by the
cholecystokinin 2 receptor.
AB - The peptide hormone gastrin (Gamide) binds trivalent metal ions, including indium
(In), ruthenium (Ru) and gallium (Ga), with high affinity. Complexes of gastrin
with chelated isotopes of In and Ga have previously been used for the location of
tumours expressing the cholecystokinin 2 receptor (CCK2R). The aim of the present
study was to purify the complexes of Gamide with radioactive isotopes of In, Ru
or Ga and to investigate their ability to bind to the CCK2R. The radioactive
Gamide complexes were purified on Sep-Pak C18 cartridges or by anion exchange
HPLC. Binding to the CCK2R was assessed with a stably transfected clone of the
gastric carcinoma cell line AGS. The 106Ru-Gamide complex could be eluted from
the C18 cartridge; the 111In-Gamide and 68Ga-Gamide complexes bound irreversibly.
All three complexes were successfully purified by anion exchange HPLC. The
failure to detect binding of the 111In-Gamide, 106Ru-Gamide and 68Ga-Gamide
complexes to the CCK2R suggests that formation of these complexes will not be
useful for the detection of tumours expressing this receptor, but may instead
provide alternative ways to block the actions of Gamide as a growth factor or a
stimulant of gastric acid secretion. The complexes between the hormone gastrin
and radioactive 111In, 106Ru or 68Ga ions were purified by anion exchange HPLC
using a NaCl gradient. The failure to detect binding of the complexes to the
cholecystokinin 2 receptor suggests that metal ion treatment may provide novel
approaches to block the biological actions of gastrin.
PMID- 28702752
TI - Proximal tibial extra-axial chordoma masquerading as renal cell carcinoma
metastasis.
AB - Chordomas are rare, locally aggressive notochordal tumors, which most frequently
occur in the neuraxis. We describe the case of a 74-year-old male with a history
of renal cell carcinoma, who presented with a slowly enlarging mass in his left
leg. While the clinical history and imaging suggested metastatic renal cell
carcinoma, immunohistochemical staining with brachyury ultimately made the
diagnosis of extra-axial chordoma. At 74 years of age, our patient is the oldest
ever reported with bony extra-axial chordoma objectively confirmed by brachyury
staining. A detailed case discussion and a review of the available literature on
this rare clinicopathologic entity are provided.
PMID- 28702753
TI - Magnifying NBI Patterns of Gastric Mucosa After Helicobacter pylori Eradication
and Its Potential Link to the Gastric Cancer Risk.
AB - BACKGROUND: Gastric cancer develops after successful H. pylori eradication in
patients with severe atrophic gastritis. We classified atrophic and non-atrophic
mucosa of gastric body using magnifying NBI endoscopy in patients after
successful H. pylori eradication. MATERIALS AND METHODS: One hundred and twenty
five patients after successful H. pylori eradication (median period after
eradication: 36 months) were enrolled. Magnifying NBI patterns in the uninvolved
gastric body were divided into the following: restored-small, round pits,
accompanied with honeycomb-like subepithelial capillary networks; atrophic-well
demarcated oval or tubulovillous pits with clearly visible coiled or wavy
vessels. The subjects were also classified into the three types: Grade 0-restored
pattern is shown in all or almost the entire area of gastric body; Grade 1
mixture of restored and atrophic pattern, there is a considerable portion of the
atrophic area in the lesser curvature; Grade 2-atrophic pattern is shown in all
or almost the entire area of the gastric body. RESULTS: Sensitivity and
specificity for atrophic type for detection of histological intestinal metaplasia
were 95.9 and 98.3%, respectively. No association was observed between the
prevalence of Grades 0, 1 and 2 and duration after eradication, while grades 1
and 2 were significantly frequent in gastric cancer patients diagnosed both
before (27/35: 77%) and after (23/31: 74%) eradication, compared to the cancer
free subjects (15/59: 25%) (P < 0.001). The grades 1 and 2 were also common in
patients who underwent H. pylori eradication for gastric ulcer. CONCLUSIONS:
Magnifying the NBI pattern well correlates with pathological status of gastric
mucosa after H. pylori eradication and may predict gastric cancer occurrence.
PMID- 28702754
TI - Endoscopic Cyanoacrylate Injection with Post-injection Audible Doppler Assessment
of Gastric Varices: A Single-Institution Experience.
AB - BACKGROUND AND AIMS: Gastric varices (GV) have higher rates of morbidity and
mortality from hemorrhage than esophageal varices. Several studies have shown the
safety and efficacy of cyanoacrylate (CA) injection for acute gastric variceal
hemorrhage. We report data from our experience with CA injection for GV before
and after routine use of post-injection audible Doppler assessment (ADA) for GV
obturation and describe long-term outcomes after this therapy. METHODS: We
retrospectively identified patients who had documented GV, underwent CA
injection, and had at least 2 weeks of follow-up. We recorded and analyzed the
survival and rebleeding rates with patient demographics, clinical data, and
endoscopy findings between two groups of patients who were categorized by CA
injection prior to and after inception of the ADA technique. RESULTS: Seventy-one
patients were identified with 16 patients analyzed in a group where ADA was not
used (Pre-ADA) and 55 analyzed where ADA was used (Post-ADA). No rebleeding
events were observed within 1 week of initial CA injection. No embolic events
were reported after any initial CA injection within 4 weeks. The rate of bleed
free survival at 1 year was 69.6% in the Pre-ADA group and 85.8% in the Post-ADA
without statistical significance. The all-cause 1-year mortality was 13.8% in the
Pre-ADA group and 10.7% in the Post-ADA group without statistical significance.
CONCLUSIONS: ADA of CA-injected GV does not appear to significantly affect
adverse events or clinical outcomes; however, our findings are limited by small
sample size and cohort proportions allowing for significant type II statistical
error. Further prospective investigation is required to determine the impact of
ADA on clinical outcomes after GV obturation.
PMID- 28702755
TI - The influence of breed and environmental factors on social and solitary play in
dogs (Canis lupus familiaris).
AB - The domestic dog is an ideal model species in which to study the genetic and
environmental factors that influence play behavior. Dogs exist in a wide variety
of breeds and frequently engage in multiple forms of play. In the present study,
we investigated whether the levels of solitary and social play differed between
dogs of three breed types with distinct predatory motor pattern sequences
(herding dogs, retrievers, and livestock guarding dogs [LGDs]). Furthermore, we
investigated how environmental factors (social and nonsocial contexts) influenced
play in dogs of these breed types. Groups of breed-matched dyads with working
experience and of equivalent age, sex, and neuter status ratios were exposed to
four experimental test conditions and two control conditions in randomized
orders. With respect to solitary play, environmental context did have a
significant effect, with toys reliably producing the highest levels of solitary
play across all breed types. Retrievers engaged in significantly higher levels of
solitary play overall than LGDs, and there was a trend in comparison to herding
dogs. In contrast, neither environmental context nor breed had a significant
effect on social play levels; however, neuter status of the dyads did have a
significant effect on social play, with mixed-status dyads engaging in
significantly higher levels of social play than same-status dyads. Our findings
provide experimental evidence for identifying proximate, environmental stimuli
that reliably facilitate social and solitary play and discuss possible genetic
(i.e., breed type) and lifetime influences on the form of play in domestic dogs.
PMID- 28702756
TI - Creating a common terminology for play behavior to increase cross-disciplinary
research.
AB - Historically, play behavior has been difficult to define. This likely stems from
the number of different species, types of play, and context under which it
occurs. In 2016, the Chicago Zoological Society - Brookfield Zoo hosted the
Psychonomic Society leading edge workshop on the evolutionary and psychological
significance of play. Sixteen experts attended from the diverse fields of African
ethnology, animal behavior, animal science, animal welfare, cognitive psychology,
cognitive zoology, comparative psychology, cultural anthropology, developmental
psychology, educational psychology, ethology, neuroscience, primatology, and
zoology. Approximately half of the participants studied human play and the other
half studied non-human play. Before the workshop, participants were asked to send
in either their personal definition of play or the one that they cite in peer
reviewed literature. Definitions were then reviewed to determine characteristics
of play inclusive of all disciplines. The goal of the current study was not to do
a literature review on play behavior, but to come up with a list of
characteristics across all forms of play that could be used as a common
terminology moving forward. Hopefully the results of this workshop and the
current article will help to increase cross-disciplinary research in the field of
play.
PMID- 28702757
TI - Mental Distress Factors and Exercise Capacity in Patients with Coronary Artery
Disease Attending Cardiac Rehabilitation Program.
AB - PURPOSE: There is still insufficient data on mental distress factors contributing
to exercise capacity (EC) improvement before and after cardiac rehabilitation
(CR) in patients with coronary artery disease (CAD). The aim of our study was to
evaluate the associations between various mental distress factors and EC before
and after exercise-based CR (EBCR). METHODS: Over 12 months, 223 CAD patients
(70% men, mean age 58 +/- 9 years) were evaluated for socio-demographic,
clinical, and mental distress symptoms as measured by the Hospital Anxiety and
Depression scale (HADS), Beck Depression Inventory-II (BDI-II), and Spielberger
State-Trait Anxiety Inventory (STAI). Patients were tested for EC at baseline and
after EBCR. RESULTS: In a multivariate linear regression model, EC before EBCR
was associated with HADS anxiety subscale (beta = -.186, p = .002) and BDI-II
somatic/affective subscale (beta = -.249, p < .001). EC after EBCR was associated
with HADS anxiety and depression subscales (beta = -.198, p < .001; beta = -.170,
p = .002, respectively) and BDI-II (beta = -.258, p < .001). The BDI-II
somatic/affective subscale was the best predictor of reduced EC before and after
EBCR. CONCLUSIONS: Mental distress and somatic/affective symptoms of depression
are strongly associated with EC both at the beginning and after EBCR. Analysis of
possible mediating or moderating factors was beyond the scope of our study.
Future studies should focus on comprehensive evaluation of EC risk factors
including other mental distress characteristics, subjectively experienced
fatigue, and post-operative CAD symptoms.
PMID- 28702758
TI - Real Time Monitoring of Engagement with a Text Message Intervention to Reduce
Binge Drinking Among Men Living in Socially Disadvantaged Areas of Scotland.
AB - PURPOSE: This study identified the extent and nature of engagement with a
theoretically based behaviour change text message intervention intended to reduce
binge drinking. The data were from a randomised controlled trial tackling binge
drinking among socially disadvantaged men. METHOD: An intervention, comprising
112 text messages, and based on the principles of the Health Action Process
Approach, was delivered to 411 socially disadvantaged men. Participants sent
almost 7500 responses to the text messages. Engagement was assessed by whether
text message replies showed the intended response to key components of the
behaviour change strategy. RESULTS: The median number of responses to the text
messages was 17 per man (range 0-81). Men often gave detailed sensitive personal
information about their drinking and the harms it caused them. They also
described their attempts at drinking less, the setbacks encountered and the
benefits they enjoy when they are successful at cutting down. Specific examples
of engagement with the targeted messages include the following: of the 248 men
who responded to the prompt on outcome expectancies, most (230) identified
potential benefits of cutting down; for intention to reduce drinking, 260 men
responded of whom 44% said they had thought about changing; of the 172 men who
responded to the question on goal setting, 158 reported personal goals.
CONCLUSIONS: The responses showed that most men engaged as intended with the key
components of the intervention. Text message interventions should include
questions addressing key components of the behaviour change strategy to determine
whether there is effective engagement with intervention components.
PMID- 28702759
TI - Evaluation of DNA damage in tobacco male meiocytes involved in cytomixis using
comet assay.
AB - Cytomixis is a process of nuclear migration between plant cells. As a rule, it is
detectable in male meiocytes and gives rise to the cells with micronuclei.
Examination of the integrity and functional state of migrating chromatin is of
great interest, since cytomixis is assumed to change the gamete karyotype. We,
for the first time, used comet assay to assess the DNA integrity in the chromatin
that migrates between plant meiocytes. As was shown, the cells involved in
cytomixis are viable and display no signs of DNA damage. Any comet tails are
undetectable in both the main nuclei of the cells involved in cytomixis and
cytomictic micronuclei. On the other hand, the cytomictic micronuclei after heat
shock (positive control) form typical comet tails.
PMID- 28702760
TI - Regulation of long-distance transport of mitochondria along microtubules.
AB - Mitochondria are cellular organelles of crucial importance, playing roles in
cellular life and death. In certain cell types, such as neurons, mitochondria
must travel long distances so as to meet metabolic demands of the cell.
Mitochondrial movement is essentially microtubule (MT) based and is executed by
two main motor proteins, Dynein and Kinesin. The organization of the cellular MT
network and the identity of motors dictate mitochondrial transport. Tight
coupling between MTs, motors, and the mitochondria is needed for the organelle
precise localization. Two adaptor proteins are involved directly in mitochondria
motor coupling, namely Milton known also as TRAK, which is the motor adaptor, and
Miro, which is the mitochondrial protein. Here, we discuss the active
mitochondria transport process, as well as motor-mitochondria coupling in the
context of MT organization in different cell types. We focus on mitochondrial
trafficking in different cell types, specifically neurons, migrating cells, and
polarized epithelial cells.
PMID- 28702761
TI - Can a hand radiograph indicate a special diagnosis in a child with chronic kidney
disease? Questions.
PMID- 28702762
TI - Successful therapy switch from eculizumab to mycophenolate mofetil in a girl with
DEAP-HUS.
PMID- 28702764
TI - The direct analysis of drug distribution of rotigotine-loaded microspheres from
tissue sections by LESA coupled with tandem mass spectrometry.
AB - The direct analysis of drug distribution of rotigotine-loaded microspheres (RoMS)
from tissue sections by liquid extraction surface analysis (LESA) coupled with
tandem mass spectrometry (MS/MS) was demonstrated. The RoMS distribution in rat
tissues assessed by the ambient LESA-MS/MS approach without extensive or tedious
sample pretreatment was compared with that obtained by a conventional liquid
chromatography tandem mass spectrometry (LC-MS/MS) method in which organ excision
and subsequent solvent extraction were commonly employed before analysis. Results
obtained from the two were well correlated for a majority of the organs, such as
muscle, liver, stomach, and hippocampus. The distribution of RoMS in the brain,
however, was found to be mainly focused in the hippocampus and striatum regions
as shown by the LESA-imaged profiles. The LESA approach we developed is sensitive
enough, with an estimated LLOQ at 0.05 ng/mL of rotigotine in brain tissue, and
information-rich with minimal sample preparation, suitable, and promising in
assisting the development of new drug delivery systems for controlled drug
release and protection. Graphical abstract Workflow for the LESA-MS/MS imaging of
brain tissue section after intramuscular RoMS administration.
PMID- 28702765
TI - Association between serum/plasma adiponectin levels and immune-mediated diseases:
a meta-analysis.
AB - Adiponectin plays an important role in the development of immune-mediated
diseases. Currently published data regarding the relationship between
serum/plasma levels of adiponectin and immune-mediated diseases are inconsistent.
We therefore conducted this meta-analysis to explore the association of
serum/plasma adiponectin levels with immune-mediated diseases in humans.
Systematic literature search was conducted to identify all relevant studies. The
study quality was assessed by the Newcastle-Ottawa scale. Pooled standard mean
difference (SMD) with 95% confidence interval (CI) was calculated by random
effect model analysis. A total of 47 studies were included in our meta-analysis,
including 27 studies of type 1 diabetes mellitus (T1DM), 9 studies of rheumatoid
arthritis (RA), 7 studies of systemic lupus erythematosus (SLE), and 4 studies of
ankylosing spondylitis (AS). The results revealed significant differences in
serum/plasma levels of adiponectin between immune-mediated diseases and normal
controls (SMD = 1.262, 95% CI 0.766-1.758, p < 0.001). In the subgroup analysis
stratified by disease type, the serum/plasma levels of adiponectin in T1DM, RA
and SLE patients were higher than those in normal control, but not in AS
patients. Moreover, in the subgroup analysis stratified by gender, in both men
and women group, the serum/plasma levels of adiponectin in patients with immune
mediated diseases were higher than that in the control group. Furthermore,
subgroup analyses also showed that immune-mediated diseases from Asian
population, Caucasian population, mean age >40 years, and BMI >=24 kg/m2 had
higher serum/plasma adiponectin levels when compared with normal controls.
Collectively, this meta-analysis demonstrates that serum/plasma levels of
adiponectin in T1DM, RA and SLE patients were higher than those in normal
controls, but not in AS patients.
PMID- 28702766
TI - Erratum to: De novo exonic duplication of ATP1A2 in Italian patient with
hemiplegic migraine: a case report.
PMID- 28702767
TI - Erratum to: Development of the Return-to-Work Obstacles and Self-Efficacy Scale
(ROSES) and Validation with Workers Suffering from a Common Mental Disorder or
Musculoskeletal Disorder.
PMID- 28702763
TI - Pharmacokinetics of antifungal drugs: practical implications for optimized
treatment of patients.
AB - INTRODUCTION: Because of the high mortality of invasive fungal infections (IFIs),
appropriate exposure to antifungals appears to be crucial for therapeutic
efficacy and safety. MATERIALS AND METHODS: This review summarises published
pharmacokinetic data on systemically administered antifungals focusing on co
morbidities, target-site penetration, and combination antifungal therapy.
CONCLUSIONS AND DISCUSSION: Amphotericin B is eliminated unchanged via urine and
faeces. Flucytosine and fluconazole display low protein binding and are
eliminated by the kidney. Itraconazole, voriconazole, posaconazole and
isavuconazole are metabolised in the liver. Azoles are substrates and inhibitors
of cytochrome P450 (CYP) isoenzymes and are therefore involved in numerous drug
drug interactions. Anidulafungin is spontaneously degraded in the plasma.
Caspofungin and micafungin undergo enzymatic metabolism in the liver, which is
independent of CYP. Although several drug-drug interactions occur during
caspofungin and micafungin treatment, echinocandins display a lower potential for
drug-drug interactions. Flucytosine and azoles penetrate into most of relevant
tissues. Amphotericin B accumulates in the liver and in the spleen. Its
concentrations in lung and kidney are intermediate and relatively low myocardium
and brain. Tissue distribution of echinocandins is similar to that of
amphotericin. Combination antifungal therapy is established for cryptococcosis
but controversial in other IFIs such as invasive aspergillosis and mucormycosis.
PMID- 28702768
TI - A Prospective Cohort Study of the Impact of Return-to-Work Coordinators in
Getting Injured Workers Back on the Job.
AB - Purpose To assess the impact of workplace-based return-to-work (RTW)
Coordinators' interpersonal and functional activities on RTW outcomes. Methods
Multivariable logistic regression analyses of cross-sectional and longitudinal
survey responses of 632 injured workers with at least 10 days of work absence in
Victoria, Australia, adjusting for demographic and other workplace factors.
Outcome was being back at work for at least 1 month, measured at both baseline
and 6 month follow-up survey. Participant responses to stressfulness of
Coordinator interactions were dichotomised into good and poor and evaluated as a
proxy for Coordinators' interpersonal activities, while having a RTW plan was
evaluated as a proxy for functional activities. Results At baseline, RTW plans
doubled the odds of RTW (OR 2.02; 95% CI 1.40-2.90) and attenuated the impact of
good Coordinator interactions (1.14; 0.77-1.70). At 6-month follow-up, the
opposite was observed: good interactions nearly doubled odds of RTW (1.90; 1.22
2.95) while RTW plans were non-significant (1.02; 0.68-1.54). Conclusions
Differences between when the two Coordinator activities were effective may be due
to the nature of claimants who RTW in each survey period. Length of shorter
duration claims are influenced by injury related factors, while psychosocial
factors tend to be more important for longer-duration claims. Such factors may
determine whether a claimant is more likely to respond to Coordinators'
functional or interpersonal activities. The findings have important implications
for increasing Coordinator effectiveness.
PMID- 28702769
TI - Short and long-term outcomes after combined intravenous thrombolysis and
mechanical thrombectomy versus direct mechanical thrombectomy: a prospective
single-center study.
AB - Recent clinical trials demonstrated that mechanical thrombectomy (MT) using
second-generation endovascular devices has beneficial effects in acute ischemic
stroke (AIS) due to large vessel occlusion (LVO). However, it remains
controversial if intravenous thrombolysis (IVT) prior to MT is superior compared
to direct mechanical thrombectomy (DMT). The aims of this study were to compare
short and long-term outcomes between IVT + MT and DMT patients. We prospectively
recruited AIS patients with LVO in the anterior or posterior circulation eligible
for MT with and without prior IVT. Modified Rankin Scale (mRS) and mortality were
assessed at baseline, at discharge, 90-days and 1-year after stroke. Favorable
outcome was defined as a mRS score <=2. Of the 66 patients included, 33 (50%)
were in IVT + MT group and 33 (50%) were in DMT group. Except for a higher
prevalence of patients using anticoagulants at admission in DMT group, baseline
characteristics did not differ in the two groups. Procedural characteristics were
similar in IVT + MT and DMT group. Rate of favorable outcome was significantly
higher in IVT + MT patients than DMT ones both 90-days (51.5 vs. 18.2%; p =
0.004) and 1-year (51.5 vs. 15.2%; p = 0.002) after stroke. DMT patients were six
times more likely to die during the 1-year follow-up compared to IVT + MT
patients. This study suggests that bridging therapy may improve short and long
term outcomes in patients eligible for endovascular treatment. Further studies
with larger patient numbers and randomized design are needed to confirm our
findings.
PMID- 28702770
TI - Oncologic Outcomes After Treatment for MRI Occult Breast Cancer (pT0N+).
AB - BACKGROUND: Studies assessing outcomes in occult breast cancer have often
included women treated before the routine use of magnetic resonance imaging
(MRI). This study examined outcomes for patients presenting with axillary
adenopathy and no primary breast tumor detectable by MRI or other imaging
methods. METHODS: All patients with axillary nodal metastases consistent with
breast carcinoma and no breast primary tumor detectable by physical exam,
mammography, or MRI treated between 1 January 1996 and 30 June 2011 were
identified from an institutional database. Data were collected on local,
regional, and distant recurrences. RESULTS: For the study, 38 patients were
identified. Modified radical mastectomy (MRM) was performed for 13 of the
patients, whereas 25 of the patients underwent axillary dissection (ALND) and
whole-breast radiotherapy (WBRT). Most of the women had pathologic N1 disease
[median number of positive nodes, 2 (MRM cohort) and 3 (ALND + WBRT cohort); p =
0.38]. All the patients received chemotherapy, and 30 (79%) of the 38 patients
received an anthracycline and taxane. Regional nodal radiation was used for 60%
of those with ALND + WBRT and for all 46% of the MRM patients who received chest
wall radiotherapy. During a median follow-up period of 7 years, there were no
nodal recurrences. Two patients treated with ALND + WBRT had in-breast
recurrences, whereas none in the MRM group experienced a local recurrence. The
proportion that experienced distant disease was similar between the MRM cohort (1
of 13) and the ALND + WBRT cohort (2 of 25). CONCLUSION: Breast cancer presenting
as axillary adenopathy with no detectable primary tumor is rare. Breast
conservation with WBRT is a viable option for patients with a diagnosis of occult
breast cancer and a negative preoperative MRI.
PMID- 28702771
TI - Evidence for the Trait-Impulsivity Etiological Model in a Clinical Sample:
Bifactor Structure and Its Relation to Impairment and Environmental Risk.
AB - The trait-impulsivity etiological model assumes that a general factor (trait
impulsivity) underlies attention-deficit/hyperactivity disorder (ADHD),
oppositional defiant disorder (ODD), and other externalizing disorders. We
investigated the plausibility of this assumption by testing the factor structure
of ADHD and ODD in a bifactor framework for a clinical sample of 1420 children
between 6 and 18 years of age (M = 9.99, SD = 3.34; 85% male). Further, the trait
impulsivity etiological model assumes that ODD emerges only if environmental risk
factors are present. Our results support the validity of the trait-impulsivity
etiological model, as they confirm that ADHD and ODD share a strong general
factor of disruptive behavior (DB) in this clinical sample. Furthermore, unlike
the subdimensions of ADHD, we found that the specific ODD factor explained as
much true score variance as the general DB factor. This suggests that a common
scale of ADHD and ODD may prove to be as important as a separate ODD subscale to
assess externalizing problems in school-age children. However, all other
subscales of ADHD may not explain sufficient true score variance once the impact
of the general DB factor has been taken into consideration. In accordance with
the trait-impulsivity model, we also showed that all factors, but predominantly
the general factor and specific inattention factor, predicted parent-rated
impairment, and that predominantly ODD and impulsivity are predicted by
environmental risk factors.
PMID- 28702772
TI - A phase II trial of erlotinib monotherapy in advanced pancreatic cancer as a
first- or second-line agent.
AB - INTRODUCTION: Pancreatic adenocarcinoma carries a grim prognosis. In 2007,
gemcitabine with erlotinib emerged as an appropriate treatment option for
patients with advanced inoperable or metastatic disease (APC). In this phase II
trial we sought to evaluate the efficacy of erlotinib monotherapy in patients
with APC who had disease refractory to or ineligibility for gemcitabine-based
therapy. METHODS: Eligible patients who had received 0 or 1 non-EGFR inhibitor
containing gemcitabine-based chemotherapy for APC were recruited prospectively
and treated with erlotinib 150 mg orally daily until unacceptable toxicity or
disease progression. Primary endpoint was progression-free survival (PFS).
Correlations of clinical response with smoking, rash, steady-state concentration
of erlotinib and its metabolite (OSI-420) as well as the nicotine metabolite
cotinine were performed. RESULTS: The trial was terminated early for futility.
Eighteen of the 34 planned subjects were recruited. Median PFS and OS were 42 and
95 days, respectively. Best response was stable disease (21%). There was a trend
for improved PFS and OS in never smokers compared to current and past smokers
(128.5, 39, 42 days and 173, 100, 88 days, respectively). Past/current smokers
had lower steady-state concentrations of erlotinib and OSI-420 compared to never
smokers. There was evidence of recent smoking exposure in 30% of patients self
identified as past smokers. Rash was infrequent, with no cases of grade III/IV
rash and it was not related to treatment outcomes. CONCLUSIONS: Overall,
erlotinib monotherapy failed to improve outcomes compared to historical controls
in patients with APC after 0-1 prior systemic therapies. There was a trend for
improved PFS and OS in never smokers.
PMID- 28702773
TI - Can exercise or physical activity help improve postnatal depression and weight
loss? A systematic review.
AB - Despite exercise or physical activity (PA) being effective on depression and
weight management generally, its effectiveness remains uncertain during
postpartum. This systematic review aimed to determine the efficacy of exercise or
PA interventions on postnatal depression (PND) and weight loss, with a subsequent
aim to identify more effective intervention approaches. Using PRISMA guidelines,
data searches conducted across six databases. Nine studies fulfilled our
inclusion criteria. Based on identified studies (some with high-quality RCT
designs), there was inconsistency as to whether exercise or PA simultaneously
reduced PND symptoms and assisted weight loss (or related body composition
indices). Two (22.2%) identified changes in both outcomes with small effect
sizes. Four studies (44.4%) reported changes in one outcome, typically PND with
variable effect sizes, while three studies (33.3%) reported no effect. Studies
implemented different exercise/PA modalities (commonly walking) and incorporated
various support strategies to assist intervention participation and adherence.
Studies identified as most likely to associate with PND and/or weight loss
changes were those with supervision (1-1, group), structure (weekly frequency,
scheduled durations and moderate intensity), which adhered to specific
exercise/PA guidelines over an extended postpartum period (e.g. 12 weeks +) and
were supplemented by several psycho-social support strategies (e.g. educational
information, exercise/PA advice, and counselling). Future studies need to
carefully address prior study methodological weaknesses (e.g. study design,
inclusion criteria, measurement, reporting, assessing confounding factors),
further examine proposed more beneficial exercise/PA intervention approaches, and
consider how exercise/PA could be best delivered in practice to benefit women's
postpartum health.
PMID- 28702774
TI - Do FSH/LH ratio and gonadal hormone levels predict clinical improvement in
postmenopausal schizophrenia women?
AB - Menopause is a process characterized by a decline in estrogen levels and is
therefore a period of biological vulnerability for psychotic relapse in women
with schizophrenia. Our goal was to correlate not only gonadal hormone levels but
also follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels with
improvement in specific clinical symptoms. Thirty-seven acutely ill
postmenopausal schizophrenia women with a newly initiated, clinically determined
change in antipsychotic medication participated in a 12-week prospective
observational outcome study. Scales used were the PANSS scale for psychotic
symptoms, the PSP for functioning, and CGI for global clinical impression.
Circulating FSH, LH, estradiol, progesterone, and testosterone serum levels were
determined by chemiluminescent immunoassay. Partial correlational analyses were
performed along with a Bonferroni significance correction (p < 0.0007). After
adjustment for confounding factors, the FSH/LH ratio correlated positively with
mean changes in PANSS positive scores, and there was a correlation with worsening
of CGI total and cognitive scores. Testosterone was also positively associated
with improvement in PANSS positive scores. However, after correction for multiple
testing, the initial correlations were no longer statistically significant. In
summary, while the hormone assays we did in this small sample did not prove to be
significantly linked to clinical improvement in any of the schizophrenia symptom
domains, we recommend further investigation of pituitary, adrenal, and gonadal
hormone ratios as potential markers of clinical improvement in this population.
PMID- 28702775
TI - Quality Indicators in Colonoscopy.
AB - OPINION STATEMENT: Colonoscopy is one of the most commonly performed endoscopic
procedures. It is the gold standard examination for work-up of colonic symptoms,
for follow-up of positive colorectal cancer screening tests and for detection and
removal of neoplastic polyps. Colonoscopy is a complex and invasive procedure
with a potential not only for colorectal cancer prevention, but also for serious
complications. Numerous factors may affect the balance of benefit versus harm of
colonoscopy, including the performance of the endoscopist. These factors are
commonly called quality indicators. As an increasing number of countries are
recommending the general population to undergo colorectal cancer screening, the
quality of colonoscopy should be considered a public health concern. Key quality
indicators have been identified, and several professional organizations have
issued recommendation statements to promote high-quality colonoscopy. To achieve
high quality, these key quality indicators must be monitored, results must be
analysed, and measures must be undertaken to correct substandard performance.
High-quality training in colonoscopy and polypectomy should be a quality
assurance priority.
PMID- 28702776
TI - Advanced chronic myelomonocytic leukemia in elderly and frail patients managed by
azacitidine in the field of clinical practice.
PMID- 28702777
TI - A cell line thought to represent mucinous breast cancer probably represents
lobular carcinoma with extracellular mucin production.
PMID- 28702778
TI - Characterization of HER2 gene amplification heterogeneity in invasive and in situ
breast cancer using bright-field in situ hybridization.
AB - The aims of this study were to evaluate and compare the HER2 gene amplification
status in invasive and adjacent in situ breast carcinoma, using bright-field in
situ hybridization, and to document the possible presence of HER2 genetic
heterogeneity (HER2-GH) in both components. A cohort of 100 primary invasive
carcinomas (IC) associated with carcinoma in situ (CIS) were evaluated for HER2
gene amplification by SISH according to the 2013 ASCO/CAP HER2 guideline. A
second cohort of all the cases with HER2-GH since the introduction of the updated
ASCO/CAP HER2 guideline was also characterized, and an evaluation of the HER2
gene amplification in the CIS component, if present, was also done. In the first
cohort, the HER2 amplification in the IC was negative in 87% of the cases and
positive in 13% of the cases, without the presence of HER2-GH. All the cases had
an associated CIS with the same HER2 status as IC, with four cases of CIS
presenting HER2-GH. In the CIS, we observed a significant relationship of HER2
gene amplification with high nuclear grade. In the four cases with HER2-GH in
CIS, two cases presented HER2 gene amplification in the IC. The second cohort
included 12 cases with HER2-GH in a total of 1243 IC cases (0.97%). Additionally,
we identified two cases associated with non-amplified CIS. HER2-GH is a rare
event in IC and can already be present in CIS, not being an important step in the
acquisition of invasive features.
PMID- 28702779
TI - Clinicopathological characteristics of fallopian tube metastases from primary
endometrial, cervical, and nongynecological malignancies: a single institutional
experience.
AB - This study was aimed at investigating the clinicopathological characteristics of
tubal metastases originating from primary endometrial, cervical, and
nongynecological malignancies. We performed a 4-year retrospective study in which
fallopian tube tissues obtained from 60 patients with tubal metastases were
examined. In addition, we compared the number of tubal metastasis cases detected
during periods of representative or whole tubal sampling. Twenty-three and 37
tubal metastases were found in cases examined after representative and whole
tubal sampling techniques, respectively. Four cases of microscopic tubal
metastases were detected via whole sampling, whereas no microscopic lesions were
identified via representative sampling. The metastatic lesions originated from 14
uterine (10, endometrium; 4, cervix) and 46 nongynecological tumors (21, colon;
15, stomach; 5, biliary; 3, appendix; 2, breast). Tumors were most commonly
involved in the muscle and lamina propria (n = 17). We noted distinctive
histopathological features according to the extent of mural involvement:
fibromyxoid stromal reaction and lymphohistiocytic infiltration in tumors
involving the muscle and subepithelial connective tissue, architectural
alterations of plicae in those involving the subepithelial connective tissue, and
intraluminal mucinous and inflammatory exudate adjacent to intraepithelial
tumors. We observed distinctive histopathological features associated with tubal
metastases according to the extent of mural involvement. In addition, we
demonstrated that the sampling method used in the routine microscopic examination
of the fallopian tube affects the detection of tubal metastases. Our data support
the notion that it is more logical to thoroughly sample both the fimbrial ends
and the nonfimbriated portions of fallopian tubes for all salpingectomy specimens
in the setting of cancer surgery.
PMID- 28702780
TI - The purine-rich element-binding protein ChPur-alpha negatively regulates Hsc70
transcription in Crassostrea hongkongensis.
AB - ChPur-alpha, a purine-rich element-binding protein, was discovered showing
affinity to the ChHsc70 promoter in Crassostrea hongkongensis by DNA affinity
purification and mass spectrometry analysis. Direct interaction between purified
ChPur-alpha and the ChHsc70 promoter region was demonstrated by electrophoretic
mobility shift assay in vitro. ChPur-alpha reduction led to clear enhancements of
ChHsc70 transcription in the hemocytes of C. hongkongensis. Consistently, ChPur
alpha overexpression in heterologous HEK293T cells correlated with repressive
phenotype in ChHsc70 promoter expression. ChHsc70 transcription was responsive to
heat shock or CdCl2 stress by RT-PCR, signifying an inducible feature of ChHsc70
transcription by physical/chemical stress despite its constitutive nature. ChPur
alpha transcription was also induced by the two stressors. This indicates a
plausible association between ChHsc70 and ChPur-alpha in the stress-induced
genetic regulatory pathway. This study discovered a negatively regulatory role of
ChPur-alpha in controlling ChHsc70 transcription in C. hongkongensis, and
contributed to better understanding the regulatory mechanisms in control of Hsc70
transcription.
PMID- 28702781
TI - Radiographic patterns of progression with associated outcomes after bevacizumab
therapy in glioblastoma patients.
AB - Treatment response and survival after bevacizumab failure remains poor in
patients with glioblastoma. Several recent publications examining glioblastoma
patients treated with bevacizumab have described specific radiographic patterns
of disease progression as correlating with outcome. This study aims to scrutinize
these previously reported radiographic prognostic models in an independent data
set to inspect their reproducibility and potential for clinical utility. Sixty
four patients treated at MD Anderson matched predetermined inclusion criteria.
Patients were categorized based on previously published data by: (1) Nowosielski
et al. into: T2-diffuse, cT1 Flare-up, non-responders and T2 circumscribed groups
(2) Modified Pope et al. criteria into: local, diffuse and distant groups and (3)
Bahr et al. into groups with or without new diffusion-restricted and/or pre
contrast T1-hyperintense lesions. When classified according to Nowosielski et al.
criteria, the cT1 Flare-up group had the longest overall survival (OS) from
bevacizumab initiation, with non-responders having the worst outcomes. The T2
diffuse group had the longest progression free survival (PFS) from start of
bevacizumab. When classified by modified Pope at al. criteria, most patients did
not experience a shift in tumor pattern from the pattern at baseline, while the
PFS and OS in patients with local-to-local and local-to-diffuse/distant patterns
of progression were similar. Patients developing restricted diffusion on
bevacizumab had worse OS. Diffuse patterns of progression in patients treated
with bevacizumab are rare and not associated with worse outcomes compared to
other radiographic subgroups. Emergence of restricted diffusion during
bevacizumab treatment was a radiographic marker of worse OS.
PMID- 28702782
TI - Immunohistochemical localization of histidine-rich glycoprotein in human skeletal
muscle: preferential distribution of the protein at the sarcomeric I-band.
AB - Histidine-rich glycoprotein (HRG) is a relatively abundant plasma protein that is
synthesized by parenchymal liver cells. Using Western blot analysis and
immunoperoxidase techniques, we have previously shown the presence of HRG in
human skeletal muscle. This paper reports the results of immunofluorescence
experiments carried out on sections of human normal skeletal muscle biopsies to
investigate the subcellular localization of HRG. The HRG localization was also
compared with that of skeletal muscle AMP deaminase (AMPD1), since we have
previously described an association of the enzyme with the protein. The obtained
results give evidence for a preferential localization of HRG at the I-band level,
where it shows the same distribution of actin and where AMPD1 is present in major
concentration.
PMID- 28702783
TI - Origins of Life Research: a Bibliometric Approach.
AB - This study explores the collaborative nature and interdisciplinarity of the
origin(s) of life (OoL) research community. Although OoL research is one of the
oldest topics in philosophy, religion, and science; to date there has been no
review of the field utilizing bibliometric measures. A dataset of 5647
publications that are tagged as OoL, astrobiology, exobiology, and prebiotic
chemistry is analyzed. The most prolific authors (Raulin, Ehrenfreund, McKay,
Cleaves, Cockell, Lazcano, etc.), most cited scholars and their articles (Miller
1953, Gilbert 1986, Chyba & Sagan 1992, Wachtershauser 1988, etc.), and popular
journals (Origins of Life and Evolution of Biospheres and Astrobiology) for OoL
research are identified. Moreover, interdisciplinary research conducted through
research networks, institutions (NASA, Caltech, University of Arizona, University
of Washington, CNRS, etc.), and keywords & concepts (astrobiology, life, Mars,
amino acid, prebiotic chemistry, evolution, RNA) are explored.
PMID- 28702784
TI - Cementless, modular, distally fixed stem in hip revision arthroplasty: a single
center study of 132 consecutive hips.
AB - PURPOSE: The use of cementless, modular, distally fixed stem in hip revision
arthroplasty has increased during the last decades. We aimed to analyze the early
and late postoperative complications, re-operation rate, and survival rate of the
MP stem operated at our county hospital with relatively limited caseload.
METHODS: In this retrospective study, we included 132 hips operated with MP stem
between January 2007-2014. An independent observer reviewed patients' medical
records in July 2015 (18-102 months postoperatively, median 52.5) to collect the
following data: age, sex, American Society of Anesthesiologists (ASA) class, body
mass index, indication of revision, type of operation, early and late
complications, re-operation rate, and mortality during study period. RESULTS: The
commonest indication for MP stem operation was aseptic loosening (72%). We found
early and late postoperative complications in 29% of cases. The most common
complication was prosthetic dislocation (8%), followed by intra-operative peri
prosthetic fracture (5%). The commonest indication for MP re-operation was soft
tissue revision for infection (7%) followed by closed reduction for prosthetic
dislocation (6%). We found no correlation between the age, sex, ASA class, and
type of operation and the re-operation risk. Only one prosthesis was extracted
giving a survival rate for 99% for the study period. CONCLUSION: This study
showed good results of the MP prosthesis with reasonable complication and re
operation rates and negligible extraction rate, indicating the good performance
of this implant even when used in the setting of a county hospital with limited
caseload.
PMID- 28702785
TI - Changes in dural sac caliber with standing MRI improve correlation with symptoms
of lumbar spinal stenosis.
AB - PURPOSE: Weight bearing does alter the dimension of lumbar spinal canal, but no
study has analyzed its clinical correlation. This study aims to evaluate whether
the changes in dural sac cross-sectional area (DSCA) and sagittal anteroposterior
(AP) diameter on standing magnetic resonance imaging (MRI) correlate better with
clinical symptoms of lumbar spinal stenosis. METHODS: Seventy consecutive
patients with neurogenic claudication were prospectively recruited to undergo a
0.25-T MRI examination performed in supine and standing positions. Clinical
symptoms including the walking distance, Visual Analogue Score of leg pain,
Chinese Oswestry Disability Index, and short form-12 were assessed. DSCA and
sagittal AP diameter at the most constricted spinal level on supine and standing
positions were measured and correlated with each clinical symptom by Pearson
correlation coefficients (r). RESULTS: DSCA and AP diameter on standing MRI and
their % changes from supine to standing showed significant (r = 0.55, 0.53,
0.44, -0.43; p < 0.001) and better correlations than those on supine MRI (r =
0.39, 0.42; p < 0.001) with walking distance. Significant correlations were also
found between dural sac calibers on standing MRI and leg pain scores (r = -0.20,
r = -0.25; p < 0.05). Patients walking <=500 m had a significantly smaller DSCA,
narrower AP diameter and greater % change in dural sac calibers (p < 0.01) than
those walking >500 m. A >30% reduction of DSCA and AP diameter was observed in
patients with worse claudication distance (p < 0.05). CONCLUSION: DSCA and
sagittal AP diameter on standing MRI correlate significantly and better than
findings on supine MRI with claudication symptoms. Standing MRI demonstrates
dynamic changes of dural sac and provides an additional value to supine MRI in
correlating clinical symptoms of lumbar spinal stenosis.
PMID- 28702786
TI - The water lily sign.
PMID- 28702787
TI - Multiparametric magnetic resonance imaging for transition zone prostate cancer:
essential findings, limitations, and future directions.
AB - OBJECTIVE: Review the multiparametric MRI (mpMRI) findings of transition zone
(TZ) prostate cancer (PCa) using T2-weighted imaging (T2WI), diffusion-weighted
imaging (DWI), and dynamic contrast-enhanced (DCE) MRI and to integrate mpMRI
findings with clinical history, laboratory values, and histopathology.
CONCLUSION: TZ prostate tumors are challenging to detect clinically and at MRI.
mpMRI using the combination of sequences has the potential to improve accuracy of
TZ cancer detection and staging.
PMID- 28702788
TI - How do physicians become medical experts? A test of three competing theories:
distinct domains, independent influence and encapsulation models.
AB - The distinction between basic sciences and clinical knowledge which has led to a
theoretical debate on how medical expertise is developed has implications for
medical school and lifelong medical education. This longitudinal, population
based observational study was conducted to test the fit of three theories
knowledge encapsulation, independent influence, distinct domains-of the
development of medical expertise employing structural equation modelling. Data
were collected from 548 physicians (292 men-53.3%; 256 women-46.7%; mean age =
24.2 years on admission) who had graduated from medical school 2009-2014. They
included (1) Admissions data of undergraduate grade point average and Medical
College Admission Test sub-test scores, (2) Course performance data from years 1,
2, and 3 of medical school, and (3) Performance on the NBME exams (i.e., Step 1,
Step 2 CK, and Step 3). Statistical fit indices (Goodness of Fit Index-GFI;
standardized root mean squared residual-SRMR; root mean squared error of
approximation-RSMEA) and comparative fit [Formula: see text] of three theories of
cognitive development of medical expertise were used to assess model fit. There
is support for the knowledge encapsulation three factor model of clinical
competency (GFI = 0.973, SRMR = 0.043, RSMEA = 0.063) which had superior fit
indices to both the independent influence and distinct domains theories
([Formula: see text] vs [Formula: see text] [[Formula: see text]] vs [Formula:
see text] [[Formula: see text]], respectively). The findings support a theory
where basic sciences and medical aptitude are direct, correlated influences on
clinical competency that encapsulates basic knowledge.
PMID- 28702789
TI - Bevacizumab plus chemotherapy for patients with advanced pulmonary adenocarcinoma
harboring EGFR mutations.
AB - PURPOSE: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors
(TKIs) and bevacizumab plus chemotherapy were effective for EGFR-mutant patients.
However, the appropriated treatment orders remained controvertible. We
investigated the efficacy of treatment orders between bevacizumab plus
chemotherapy and EGFR-TKIs for EGFR-mutant patients with advanced pulmonary
adenocarcinoma. PATIENTS AND METHODS: This study involved 40 EGFR-mutant patients
with advanced pulmonary adenocarcinoma who were treated with bevacizumab plus
carboplatin and paclitaxel (Bev + CP) and EGFR-TKIs in different treatment orders
or gemcitabine plus cisplatin (GP) in first-line setting. Seventeen patients were
treated with Bev + CP and 10 cases with GP in first-line treatment. Thirteen
patients received EGFR-TKIs after first-line Bev + CP regimen, while 13 patients
were treated with first-line EGFR-TKIs. Progression-free survival (PFS), the
response rate (ORR) and overall survival (OS) were evaluated. RESULTS: Median PFS
of Bev + CP treatment was significantly longer in first-line than non-first-line
settings (11.7 vs. 5.6 months, P = 0.003). Median OS was 37.8 months for EGFR
mutant patients with first-line Bev + CP followed by second-line EGFR-TKIs and
31.0 months for those with first-line EGFR-TKIs and non-first-line Bev + CP,
respectively (P = 0.509). Median PFS was 11.7 (95% CI 10.6-12.8) months for Bev +
CP group and 4.7 (95% CI 4.4-5.0) months for GP group with the hazard ratio of
0.17 (P = 0.001). ORR was 70.6 and 50.0% in the two groups, respectively (P =
0.415). However, there was no significant difference in median OS (33.7 vs 27.8
months, P = 0.293). CONCLUSIONS: First-line Bev + CP followed by EGFR-TKIs might
possibly provide favorable prognosis for EGFR-mutant patients. Bev + CP regimen
significantly prolonged PFS in first-line than non-first-line settings. These
findings warrant further investigations.
PMID- 28702790
TI - Heavy metal-induced oxidative stress on seed germination and seedling
development: a critical review.
AB - Heavy metal contamination in soils can influence plants and animals, often
leading to toxicosis. Heavy metals can impact various biochemical processes in
plants, including enzyme and antioxidant production, protein mobilization and
photosynthesis. Hydrolyzing enzymes play a major role in seed germination.
Enzymes such as acid phosphatases, proteases and alpha-amylases are known to
facilitate both seed germination and seedling growth via mobilizing nutrients in
the endosperm. In the presence of heavy metals, starch is immobilized and
nutrient sources become limited. Moreover, a reduction in proteolytic enzyme
activity and an increase in protein and amino acid content can be observed under
heavy metal stress. Proline, is an amino acid which is essential for cellular
metabolism. Numerous studies have shown an increase in proline content under
oxidative stress in higher plants. Furthermore, heat shock protein production has
also been observed under heavy metal stress. The chloroplast small heat shock
proteins (Hsp) reduce photosynthesis damage, rather than repair or help to
recover from heavy metal-induced damage. Heavy metals are destructive substances
for photosynthesis. They are involved in destabilizing enzymes, oxidizing
photosystem II (PS II) and disrupting the electron transport chain and mineral
metabolism. Although the physiological effects of Cd have been investigated
thoroughly, other metals such as As, Cr, Hg, Cu and Pb have received relatively
little attention. Among agricultural plants, rice has been studied extensively;
additional studies are needed to characterize toxicities of different heavy
metals on other crops. This review summarizes the current state of our
understanding of the effects of heavy metal stress on seed germination and
seedling development and highlights informational gaps and areas for future
research.
PMID- 28702791
TI - Erratum to: Identification and characterization of EYK1, a key gene for
erythritol catabolism in Yarrowia lipolytica.
PMID- 28702792
TI - Biotransformation of chlorpyrifos and endosulfan by bacteria and fungi.
AB - Large quantities of pesticides are applied on crops to protect them from pests in
modern agricultural practices around the globe. The two insecticides,
chlorpyrifos, belonging to the organophosphorous group and endosulfan, belonging
to the organochlorine group, are vastly used insecticides on agricultural crops
in the last three decades. Hence, both these insecticides are ubiquitous in the
environment. Once applied, these two insecticides undergo transformation in the
environment either biologically or non-biologically. Microbial degradation has
been considered a safe and cost-effective method for removing contaminants from
the environment. Both the insecticides have been subjected to biodegradation
studies using various bacteria and fungi by the researchers. Here, in this
review, we report on biotransformed products formed during the course of
biodegradation of these two insecticides and also discuss about the aftereffects
of their transformed metabolites. This is important, because the primary
biotransformed metabolites 3,5,6, trichloro-2-pyridinol of chlorpyrifos and
endosulfan sulfate of endosulfan are toxic as their parent compounds and are
noxious to variety of organisms. In conclusion, it is recommended to obtain
microbial cultures capable of mineralizing pesticides completely without
formation of any such toxic by-product before adopting bioremediation or
bioaugmentation technology.
PMID- 28702793
TI - The gut eukaryotic microbiota influences the growth performance among
cohabitating shrimp.
AB - Increasing evidence has revealed a close interplay between the gut bacterial
communities and host growth performance. However, until recently, studies
generally ignored the contribution of eukaryotes, endobiotic organisms. To fill
this gap, we used Illumina sequencing technology on eukaryotic 18S rRNA gene to
compare the structures of gut eukaryotic communities among cohabitating retarded,
overgrown, and normal shrimp obtained from identically managed ponds. Results
showed that a significant difference between gut eukaryotic communities differed
significantly between water and intestine and among three shrimp categories.
Structural equation modeling revealed that changes in the gut eukaryotic
community were positively related to digestive enzyme activities, which in turn
influenced shrimp growth performance (lambda = 0.97, P < 0.001). Overgrown shrimp
exhibited a more complex and cooperative gut eukaryotic interspecies interaction
than retarded and normal shrimp, which may facilitate their nutrient acquisition
efficiency. Notably, the distribution of dominant eukaryotic genera and shifts in
keystone species were closely concordant with shrimp growth performance. In
summary, this study provides an integrated overview on direct roles of gut
eukaryotic communities in shrimp growth performance instead of well-studied
bacterial assembly.
PMID- 28702794
TI - Soil anammox community structure in different land use soils treatment with 13C
urea as determined by analysis of phospholipid fatty acids.
AB - The anaerobic ammonium oxidation (anammox) process is globally an important
nitrogen-cycling process mediated by specialized microbes. However, still little
information is documented about anammox microbial community structure under
agricultural soils. The anaerobic incubation experiment was conducted to study
the impacts of different land use soils fertilized by 13C-urea on the activity
and diversity of anammox bacteria using stable isotope to probe the phospholipid
fatty acid (PLFA-SIP). The 13C was preferentially incorporated in ratios PLFAs
16:1omega7c, 16:1omega5c, and 16:0. The results revealed that the abundance of
the anammox bacteria (both hzs-beta and hzo) were observed in vegetable soil V1
and paddy soils (R1 and R2) means that they were positively correlated with 13C
urea but were negatively correlated with NO3--N and NH4+-N concentrations. Thus,
13C-PLFAs 16:1omega7c, 16:1omega5c, and 16:0 could be the biomarker as soil
anammox. The anaerobic microbial community composition of soils under different
land use systems was diverse, and V1, R1, and R2 had similar microbial diversity
and higher microbial biomass. The principal component analysis between soil
properties and gene abundance suggested that not only pH but also soil organic
matter, available P, and available K were important factors for the anammox
process. This study suggested that 13C-Urea-PLFA for anaerobic incubation was a
simple method to study anammox microbial community structure through affecting
the soil nutrients, and the different land use systems played important roles in
determining the microbial composition of soils.
PMID- 28702795
TI - Production of trans-2,3-dihydro-3-hydroxyanthranilic acid by engineered
Pseudomonas chlororaphis GP72.
AB - Trans-2,3-dihydro-3-hydroxyanthranilic acid (DHHA) is a cyclic beta-amino acid
that can be used for the synthesis of chiral materials and nonnatural peptides.
The aim of this study was to accumulate DHHA by engineering Pseudomonas
chlororaphis GP72, a nonpathogenic strain that produces phenazine-1-carboxylic
acid and 2-hydroxyphenazine. First, the phzF deletion mutant DA1 was constructed,
which produced 1.91 g/L DHHA. Moreover, rpeA and pykF were disrupted and then
ppsA and tktA were co-expressed in strain DA1. The resulting strain DA4 increased
DHHA concentration to 4.98 g/L, which is 2.6-fold than that of DA1. The effects
of the addition of glucose, glycerol, L-tryptophan, and Fe3+on DHHA production
were also investigated. Strain DA4 produced 7.48 g/L of DHHA in the culture
medium in the presence of 12 g/L glucose and 3 mM Fe3+, which was 1.5-fold higher
than the strain in the original fermentation conditions. These results indicate
the potential of P. chlororaphis GP72 as a DHHA producer.
PMID- 28702796
TI - Accuracy of isolated-check visual evoked potential technique for diagnosing
primary open-angle glaucoma.
AB - PURPOSE: The aim of this study was to determine the diagnostic accuracy,
sensitivity and specificity of isolated-check visual evoked potentials (icVEP) in
primary open-angle glaucoma (POAG). METHODS: Ninety POAG patients and sixty-six
healthy controls were recruited consecutively. All subjects underwent icVEP and
visual field testing. Swept icVEP response functions were obtained by increasing
contrast in six stimulus steps, recording the electroencephalogram synchronized
to the stimulus display's frame rate and calculating the corresponding signal-to
noise ratio (SNR) of the response at the fundamental frequency to evaluate visual
function. Depth of modulation of the check luminance was increased as follows: 2,
4, 8, 14, 22 and 32%, about an equal level of standing contrast, so that the
pattern appeared and disappeared at a frequency of 10.0 Hz. SNR above 0.85 was
deemed to be significant at the 0.1 level and SNR above 1 significant at the 0.05
level. RESULTS: The results show that SNR is contrast dependent. It significantly
rose as contrast increased. The areas under receiver-operating-characteristic
curves (AUCs) indicating classification accuracy for all POAG cases in comparison
with normal subjects were 0.790 (sensitivity 91.1%, specificity 69.7%) with the
cutoff SNR of 0.85, and 0.706 (sensitivity 95.6%, specificity 51.5%) with the
cutoff SNR of 1. The AUC of early glaucoma cases (EG) in comparison with normal
subjects was 0.801 (sensitivity 93.3%, specificity 69.7%) with the cutoff SNR of
0.85, and 0.717 (sensitivity 97.8%, specificity 51.5%) with the cutoff SNR of 1.
CONCLUSION: icVEP has good diagnostic accuracy (high sensitivity and moderate
specificity) in distinguishing early POAG patients from healthy subjects. It
might be a promising device to use in conjunction with complementary functional
and structural measures for early POAG detection.
PMID- 28702797
TI - Purification and antibacterial mechanism of fish-borne bacteriocin and its
application in shrimp (Penaeus vannamei) for inhibiting Vibrio parahaemolyticus.
AB - Vibrio parahaemolyticus: is recognized as the main cause of gastroenteritis
associated with consumption of seafood. Bacteriocin-producing Lactobacillus
plantarum FGC-12 isolated from golden carp intestine had strong antibacterial
activity toward V. parahaemolyticus. The fish-borne bacteriocin was purified by a
three-step procedure consisting of ethyl acetate extraction, gel filtration
chromatography and high performance liquid chromatography. Its molecular weight
was estimated at 4.1 kDa using SDS-PAGE. The fish-borne bacteriocin reached the
maximum production at stationary phase after 20 h. It was heat-stable (30 min at
121 degrees C) and remained active at pH range from 3.0 to 5.5, but was
sensitive to nutrasin, papain and pepsin. Its minimum inhibitory concentration
for V. parahaemolyticus was 6.0 mg/ml. Scanning electron microscopy analysis
showed that the fish-borne bacteriocin disrupted cell wall of V.
parahaemolyticus. The antibacterial mechanism of the fish-borne bacteriocin
against V. parahaemolyticus might be described as action on membrane integrity in
terms of the leakage of electrolytes, the losses of Na+K+-ATPase, AKP and
proteins. The addition of the fish-borne bacteriocin to shrimps leaded V.
parahaemolyticus to reduce 1.3 log units at 4 degrees C storage for 6 day.
Moreover, a marked decline in total volatile base nitrogen and total viable
counts was observed in bacteriocin treated samples than the control. It is clear
that this fish-borne bacteriocin has promising potential as biopreservation for
the control of V. parahaemolyticus in aquatic products.
PMID- 28702798
TI - The Differential Absorption of a Series of P-Glycoprotein Substrates in Isolated
Perfused Lungs from Mdr1a/1b Genetic Knockout Mice can be Attributed to Distinct
Physico-Chemical Properties: an Insight into Predicting Transporter-Mediated,
Pulmonary Specific Disposition.
AB - PURPOSE: To examine if pulmonary P-glycoprotein (P-gp) is functional in an intact
lung; impeding the pulmonary absorption and increasing lung retention of P-gp
substrates administered into the airways. Using calculated physico-chemical
properties alone build a predictive Quantitative Structure-Activity Relationship
(QSAR) model distinguishing whether a substrate's pulmonary absorption would be
limited by P-gp or not. METHODS: A panel of 18 P-gp substrates were administered
into the airways of an isolated perfused mouse lung (IPML) model derived from
Mdr1a/Mdr1b knockout mice. Parallel intestinal absorption studies were performed.
Substrate physico-chemical profiling was undertaken. Using multivariate analysis
a QSAR model was established. RESULTS: A subset of P-gp substrates (10/18)
displayed pulmonary kinetics influenced by lung P-gp. These substrates possessed
distinct physico-chemical properties to those P-gp substrates unaffected by P-gp
(8/18). Differential outcomes were not related to different intrinsic P-gp
transporter kinetics. In the lung, in contrast to intestine, a higher degree of
non-polar character is required of a P-gp substrate before the net effects of
efflux become evident. The QSAR predictive model was applied to 129 substrates
including eight marketed inhaled drugs, all these inhaled drugs were predicted to
display P-gp dependent pulmonary disposition. CONCLUSIONS: Lung P-gp can affect
the pulmonary kinetics of a subset of P-gp substrates. Physico-chemical
relationships determining the significance of P-gp to absorption in the lung are
different to those operative in the intestine. Our QSAR framework may assist
profiling of inhaled drug discovery candidates that are also P-gp substrates. The
potential for P-gp mediated pulmonary disposition exists in the clinic.
PMID- 28702799
TI - Greater occipital nerve infiltration under MR guidance: Feasibility study and
preliminary results.
AB - OBJECTIVE: To assess the feasibility of greater occipital nerve (GON)
intermediate site infiltration with MRI guidance. METHODS: Eleven consecutive
patients suffering from chronic refractory cranio-facial pain who underwent 16
GON infiltrations were included in this prospective study. All of the procedures
were performed on an outpatient basis in the research facility of our
institution, with a 1.5 T scanner. The fatty space between inferior obliquus and
semispinalis muscles at C1-C2 level was defined as the target. Technical success
was defined as the ability to accurately inject the products at the target,
assessed by post-procedure axial and sagittal proton density-weighted sequences.
Clinical success was defined as a 50% pain decrease at 1 month. RESULTS:
Technical success was 100%. GON was depicted in 6/11 cases on planning MRI
sequences. Mean duration of procedure was 22.5 min (range 16-41). Clinical
success was obtained in 7/11 included patients (63.6%) with a mean self-reported
improvement of 78%. CONCLUSION: Interventional MR-guidance for GON infiltration
is a feasible technique offering similar results to an already established
effective procedure. It may appear as a useful tool in specific populations, such
as young patients and repeat infiltrations, and should be considered in these
settings. KEY POINTS: * MR guidance for GON infiltration is a feasible technique.
* Preliminary results are in agreement with other guidance modalities. * MR
guidance may be seen as a useful tool in specific populations. * Specific
populations include young patients and repeat infiltrations. * Target patients
may also include patients with potentionally previously reported complications
(torticollis).
PMID- 28702800
TI - Anterolateral ligament injuries in knees with an anterior cruciate ligament tear:
Contribution of ultrasonography and MRI.
AB - OBJECTIVES: To describe the pathological appearance of the anterolateral ligament
(ALL) on US and MRI in knees with an anterior cruciate ligament (ACL) tear.
METHODS: This prospective study included 30 patients who had a suspected acute
ACL tear. Their injured and contralateral knees were evaluated with radiography,
US and MRI. Two radiologists evaluated the ALL on the MRI and US examinations.
Agreement between these examiners' findings was evaluated with Cohen's kappa.
RESULTS: On US examination, the ALL was found to be injured in 63% of cases
(19/30; k = 0.93). The enthesis was found to be torn in 50% of cases (15/30; k =
1), with the tear located at the tibial attachment in all instances. On the MRI
exam, the ALL was found to be injured in 53% of cases (16/30; k = 0.93). The
enthesis was found to be torn in 13% of cases (4/30; k = 0.76), with the tear
located at the tibial attachment in all instances (k = 0.93). CONCLUSION: ALL
injuries that occur with ACL tears are located at the tibial enthesis. They are
often associated with bone avulsion at the enthesis and are better viewed on US.
KEY POINTS: * ALL injuries often occur in combination with ACL tears. * ALL
injuries can be assessed with ultrasonography and MRI. * ALL injuries associated
with ACL tears are located at the tibial enthesis.
PMID- 28702801
TI - Exposure to Anisakis extracts can induce inflammation on in vitro cultured human
colonic cells.
AB - Anisakis spp. is a parasitic nematode whose infective third-stage larvae may be
found within the flesh of fish species commonly consumed by humans. Thorough
cooking or freezing should render the fish safe for consumption; furthermore,
marinating solutions containing biocidal agents might have a significant action
against Anisakis larvae. Some studies suggest a relationship between some
parasitic infections and development of inflammatory bowel disorders, and
Anisakis infection might be a risk factor for stomach or colon cancer. The aim of
our study was to investigate if crude extracts (CEs) obtained from Anisakis
larvae marinated in a solution with added allyl isothiocyanate (ACE-AITC) and
frozen, or from frozen only Anisakis larvae (ACE), can induce an inflammatory
effect on in vitro differentiated colonic Caco-2 cells exposed or not to LPS.
Caco-2 exposure to the two CEs induced a marked COX-2 expression and potentiated
LPS-induced COX-2 overexpression, confirming that substances present in Anisakis
larvae can induce an inflammatory response in the intestinal epithelium, possibly
also exacerbating the effects of other inflammatory stimuli. ACE induced a marked
decrease in caspase-3 activation, while AITC-ACE increased its activation.
However, LPS-induced caspase-3 activation appeared lower in cells treated with
ACE and with the lower concentration of AITC-ACE. Thus, it is evident that
Anisakis CEs may affect various cell pathways crucial not only in the
inflammatory process but also in cell growth and death. Thus, CEs obtained from
nonviable Anisakis larvae retain or are otherwise provided with noxious
properties able to induce a strong inflammation response in intestinal epithelial
cells. Furthermore, their influence may persist also following pretreatment with
the biocidal agent AITC, indicating that the harmful substances contained in
crude extracts from Anisakis larvae are resistant to the thermal or biocidal
agent treatments.
PMID- 28702802
TI - Morphological, ultrastructural, and molecular characterization of intestinal
tetratrichomonads isolated from non-human primates in southeastern Brazil.
AB - Non-human primates are our closest relatives and represent an interesting model
for comparative parasitological studies. However, research on this topic
particularly in relation to intestinal parasites has been fragmentary and limited
mainly to animals held in captivity. Thus, our knowledge of host-parasite
relationships in this species-rich group of mammals could be considered
rudimentary. The current study combined morphological, ultrastructural, and
molecular analyses to characterize isolates of intestinal tetratrichomonads
recovered from the feces of three species of South American, non-human primates.
Fecal samples were collected from 16 animals, representing 12 distinct species.
Parabasalid-like organisms were evident in five samples (31%) of feces: two from
Alouatta sara, two from Callithrix penicillata, and one from Sapajus apella. The
five samples presented morphologies consistent with the description of
Tetratrichomonas sp., with four anterior flagella of unequal length, a well
developed undulating membrane, and a long recurrent flagellum. Sequencing of the
ITS1-5.8S rRNA-ITS2 region demonstrated that the isolates from A. sara, and C.
penicillata were closely related and highly similar to isolates of
Tetratrichomonas brumpti, recovered previously from tortoises (Geochelone sp.).
The flagellate recovered from S. apella demonstrated a similar morphology to
those of the other isolates, however, sequence analysis showed it to be identical
to an isolate of Tetratrichomonas sp. recovered from white-lipped peccaries
(Tayassu pecari). The findings of this study extend and enhance our knowledge of
parasitism of non-human primates by members of the genus Tetratrichomonas and
indicate that the host range of these parasites is broader than previously
believed.
PMID- 28702804
TI - The DFT-NEGF scrutiny of doped fullerene junctions.
AB - Using the smallest non-classical fullerene, we investigate the impact of doping
at the molecule-electrode interface on the electron transport of molecular
junctions. This is accomplished by employing the density functional theory
combined with the non-equilibrium Green's function. We contemplate different
electronic parameters, namely, density of states, transmission coefficient,
energy levels, molecular orbitals, conduction gaps, electron density, and their
charge transfer. The relevance of these physical parameters is obtained to
calculate their electrical parameters, current, and conductance, computed from
Landauer-Buttiker formalism. The molecule-electrode coupling is influenced by the
nature of doping atoms and affects the junction devices in a unique course. A
particular aftermath is noticed in Au-C18O2-Au device with highest ballistic
transport despite the electro-negative nature of oxygen atoms. Moreover, an
interesting feature is observed in Au-C18Be2-Au device with double-barrier
transmission resonance and corresponding oscillating conductance. Graphical
abstract The doped C20 fullerene in molecular and device mode.
PMID- 28702805
TI - The functionalization of carbon nanotubes to enhance the efficacy of the
anticancer drug paclitaxel: a molecular dynamics simulation study.
AB - Carbon nanotubes (CNTs) are widely used in drug delivery systems (DDSs) due to
their unique chemical and physical properties. Investigation of interactions
between biomolecules and CNTs is an interesting and important subject in
biological applications. In this study, we used molecular dynamics (MD)
simulation to investigate the adsorption mechanism of the anticancer drug
paclitaxel (PTX) on pristine and functionalized CNTs (f-CNT) in aqueous
solutions. Our theoretical results show that PTX can be adsorbed on sidewalls of
CNT in different methods. In the case of f-CNTs, PTX can be adsorbed on the
functional groups due to the existence of polar interactions. These interactions
in the CNT functionalized with polyethylene glycol (PEG), are more than the other
investigated systems. Furthermore, it was found that the solubility of CNTs in
aqueous solution is increased by functionalization. This is related to the
intermolecular hydrogen bonds between functional groups and solvent molecules.
The PEG group has the greatest effect on the solubility of the CNT in aqueous
solution due to more polar interactions.
PMID- 28702806
TI - Efficacy and Safety of Nintedanib Plus Docetaxel in Patients with Advanced Lung
Adenocarcinoma: Complementary and Exploratory Analyses of the Phase III LUME-Lung
1 Study.
AB - BACKGROUND: Nintedanib is a triple angiokinase inhibitor approved with docetaxel
for adenocarcinoma non-small cell lung cancer after first-line chemotherapy
(FLT). In the phase III LUME-Lung 1 study, overall survival (OS) was
significantly longer with nintedanib/docetaxel than with placebo/docetaxel in all
adenocarcinoma patients and those with time from start of FLT (TSFLT) <9 months.
OBJECTIVE: This study sought to extend analyses from the LUME-Lung 1 study,
specifically for adenocarcinoma patients, to explore the impact of clinically
relevant characteristics on outcomes such as time to progression after FLT.
PATIENTS AND METHODS: Exploratory analyses were conducted of the overall and
European LUME-Lung 1 adenocarcinoma population according to age, prior therapy,
and tumor dynamics. Analyses also used TSFLT and time from end of FLT (TEFLT).
RESULTS: Treatment with nintedanib/docetaxel significantly improved OS in
European patients independently of age or prior therapy. Analyses of several
patient subgroups showed improvements in median OS: TSFLT <6 months, 9.5 versus
7.5 months (hazard ratio [HR] 0.73, 95% confidence interval [CI] 0.55-0.98);
chemorefractory to FLT, 9.1 versus 6.9 months (HR 0.72, 95% CI 0.52-0.99);
progressive disease (PD) as best response to FLT, 9.8 versus 6.3 months (HR 0.62,
95% CI 0.41-0.94); TEFLT <=6 months, 11.3 versus 8.2 months (HR 0.75, 95% CI 0.61
0.92); and TEFLT <3 months, 11.0 versus 8.0 months (HR 0.74, 95% CI 0.58-0.94).
CONCLUSIONS: Nintedanib/docetaxel demonstrated significant OS benefits in
adenocarcinoma patients, which were more pronounced in patients with shorter
TSFLT or TEFLT, or with PD as best response to FLT. This study was registered at
ClinicalTrials.gov: NCT00805194.
PMID- 28702807
TI - Effect of rest-pause vs. traditional bench press training on muscle strength,
electromyography, and lifting volume in randomized trial protocols.
AB - PURPOSE: Rest-pause (4-s unloaded rest between repetitions) training effects on
one repetition maximum (1 RM), lifting volume, and neural activation via
electromyography (EMG) are currently vague in the literature and can benefit
strength and conditioning professionals for resistance training programme design.
Therefore, this study compared 1 RM, neural activation via (EMG), and volume
differences between rest-pause vs. traditional resistance training. METHODS:
Trained males (N = 20) were randomly assigned to either a rest-pause or a
traditional training group. Pre- and post-1 RM testing was recorded. Training
sessions were completed twice a week for 4 weeks and consisted of four sets of
bench press to volitional fatigue at 80% of pre-test 1 RM with a 2-min rest
between sets. Total volume completed was recorded on each training day. Neural
activation of the pectoralis major was measured on the first and last training
days. RESULTS: A two-way repeated-measures ANOVA indicated both groups
significantly increased their 1 RMs following the 4-week training protocol (p <
.05). However, no significant differences were found in 1 RM and neural
activation between the two groups (p > .05). An independent samples t test
indicated that total volume lifted was significantly higher for the rest-pause
group (56,778 vs. 38,315 lbs; p < .05) throughout the protocol and independently
during weeks 2, 3, and 4. CONCLUSIONS: While strength and neural activation
changes did not differ between groups, both increased 1 RMs and the rest-pause
group achieved greater increases in volume than the traditional group. If volume
is the focus of training, the rest-pause method should be utilized.
PMID- 28702808
TI - Longer exercise duration delays post-exercise recovery of cardiac parasympathetic
but not sympathetic indices.
AB - PURPOSE: This study investigated non-invasive indices of post-exercise
parasympathetic reactivation (using heart rate variability, HRV) and sympathetic
withdrawal (using systolic time intervals, STI) following different exercise
durations. METHODS: 13 healthy males (age 26.4 +/- 4.7 years) cycled at 70% heart
rate (HR) reserve for two durations-8 min (SHORT) and 32 min (LONG)-on separate
occasions: HRV (including natural logarithm of root mean square of successive
differences, Ln-RMSSD) and STI (including pre-ejection period, PEP) were assessed
throughout 10 min seated recovery. RESULTS: Exercise HR was similar between SHORT
and LONG (146 +/- 7 and 147 +/- 6 b min-1, respectively; p = 0.173), as was HR
deceleration during 10 min recovery (p = 0.199). HR remained elevated above
baseline (p < 0.001) throughout recovery for both trials (SHORT 82 +/- 13 b min
1; LONG 86 +/- 10 b min-1, at 10 min post-exercise). Ln-RMSSD was similar at end
exercise between trials (SHORT 1.10 +/- 0.30 ms; LONG 1.05 +/- 0.73 ms; p =
0.656), though it recovered more rapidly following SHORT (p = 0.010), with
differences apparent from 1 min (SHORT 2.29 +/- 1.08 ms; LONG 1.85 +/- 0.82 ms; p
= 0.005) to 10 min post-exercise (SHORT 2.89 +/- 0.80 ms; LONG 2.46 +/- 0.70 ms;
p = 0.007). Ln-RMSSD remained suppressed below baseline throughout recovery
following both trials (p < 0.001). PEP was the same at end exercise for both
trials (70 +/- 6 ms), with exercise duration having no effect on recovery (p =
0.659). By 10 min post-exercise, PEP increased to 130 +/- 21 ms (SHORT) and 131
+/- 20 ms (LONG), which was similar to baseline (p >= 0.143). CONCLUSIONS:
Prolonged exercise duration attenuated the recovery of HRV indices of
parasympathetic reactivation, but did not influence STI indices of sympathetic
withdrawal. Therefore, duration must be considered when investigating post
exercise HRV. Monitoring these measures simultaneously can provide insights not
revealed by underlying HR or either measure alone.
PMID- 28702809
TI - Beta2-adrenergic stimulation increases energy expenditure at rest, but not during
submaximal exercise in active overweight men.
AB - PURPOSE: beta2-Agonists have been proposed as weight-loss treatment, because they
elevate energy expenditure. However, it is unknown what effect beta2-agonists
have on energy expenditure in overweight individuals. Furthermore, the influence
of beta2-agonist R- and S-enantiomer ratio for the increased energy expenditure
is insufficiently explored. METHODS: Nineteen males were included in the study of
which 14 completed. Subjects were 31.6 (+/-3.5) years [mean (+/-95% CI)] and had
a fat percentage of 22.7 (+/-2.1)%. On separate days, subjects received either
placebo or inhaled racemic (rac-) formoterol (2 * 27 ug). After an overnight
fast, energy expenditure and substrate oxidation were estimated by indirect
calorimetry at rest and during submaximal exercise. Plasma (R,R)- and (S,S)
formoterol enantiomer levels were measured by ultra-performance liquid
chromatograph-mass spectrometry. RESULTS: At rest, energy expenditure and fat
oxidation were 12% (P <= 0.001) and 38% (P = 0.006) higher for rac-formoterol
than placebo. Systemic (R,R):(S,S) formoterol ratio was correlated with change in
energy expenditure at rest in response to rac-formoterol (r = 0.63, P = 0.028),
whereas no association was observed between fat percentage and rac-formoterol
induced change in energy expenditure. During exercise, energy expenditure was not
different between treatments, although carbohydrate oxidation was 15% higher (P =
0.021) for rac-formoterol than placebo. Rac-formoterol-induced shift in substrate
choice from rest to exercise was related to plasma ln-rac-formoterol
concentrations (r = 0.75, P = 0.005). CONCLUSION: Selective beta2-adrenoceptor
agonism effectively increases metabolic rate and fat oxidation in overweight
individuals. The potential for weight loss induced by beta2-agonists may be
greater for R-enantiopure formulations.
PMID- 28702810
TI - Epidemiology of gestational diabetes mellitus according to IADPSG/WHO 2013
criteria among obese pregnant women in Europe.
AB - AIMS/HYPOTHESIS: Accurate prevalence estimates for gestational diabetes mellitus
(GDM) among pregnant women in Europe are lacking owing to the use of a multitude
of diagnostic criteria and screening strategies in both high-risk women and the
general pregnant population. Our aims were to report important risk factors for
GDM development and calculate the prevalence of GDM in a cohort of women with BMI
>=29 kg/m2 across 11 centres in Europe using the International Association of the
Diabetes and Pregnancy Study Groups (IADPSG)/WHO 2013 diagnostic criteria.
METHODS: Pregnant women (n = 1023, 86.3% European ethnicity) with a BMI >=29.0
kg/m2 enrolled into the Vitamin D and Lifestyle Intervention for GDM Prevention
(DALI) pilot, lifestyle and vitamin D studies of this pan-European multicentre
trial, attended for an OGTT during pregnancy. Demographic, anthropometric and
metabolic data were collected at enrolment and throughout pregnancy. GDM was
diagnosed using IADPSG/WHO 2013 criteria. GDM treatment followed local policies.
RESULTS: The number of women recruited per country ranged from 80 to 217, and the
dropout rate was 7.1%. Overall, 39% of women developed GDM during pregnancy, with
no significant differences in prevalence across countries. The prevalence of GDM
was high (24%; 242/1023) in early pregnancy. Despite interventions used in the
DALI study, a further 14% (94/672) had developed GDM when tested at mid gestation
(24-28 weeks) and 13% (59/476) of the remaining cohort at late gestation (35-37
weeks). Demographics and lifestyle factors were similar at baseline between women
with GDM and those who maintained normal glucose tolerance. Previous GDM (16.5%
vs 7.9%, p = 0.002), congenital malformations (6.4% vs 3.3%, p = 0.045) and a
baby with macrosomia (31.4% vs 17.9%, p = 0.001) were reported more frequently in
those who developed GDM. Significant anthropometric and metabolic differences
were already present in early pregnancy between women who developed GDM and those
who did not. CONCLUSIONS/INTERPRETATION: The prevalence of GDM diagnosed by the
IADPSG/WHO 2013 GDM criteria in European pregnant women with a BMI >=29.0 kg/m2
is substantial, and poses a significant health burden to these pregnancies and to
the future health of the mother and her offspring. Uniform criteria for GDM
diagnosis, supported by robust evidence for the benefits of treatment, are
urgently needed to guide modern GDM screening and treatment strategies.
PMID- 28702811
TI - A machine learning framework involving EEG-based functional connectivity to
diagnose major depressive disorder (MDD).
AB - Major depressive disorder (MDD), a debilitating mental illness, could cause
functional disabilities and could become a social problem. An accurate and early
diagnosis for depression could become challenging. This paper proposed a machine
learning framework involving EEG-derived synchronization likelihood (SL) features
as input data for automatic diagnosis of MDD. It was hypothesized that EEG-based
SL features could discriminate MDD patients and healthy controls with an
acceptable accuracy better than measures such as interhemispheric coherence and
mutual information. In this work, classification models such as support vector
machine (SVM), logistic regression (LR) and Naive Bayesian (NB) were employed to
model relationship between the EEG features and the study groups (MDD patient and
healthy controls) and ultimately achieved discrimination of study participants.
The results indicated that the classification rates were better than chance. More
specifically, the study resulted into SVM classification accuracy = 98%,
sensitivity = 99.9%, specificity = 95% and f-measure = 0.97; LR classification
accuracy = 91.7%, sensitivity = 86.66%, specificity = 96.6% and f-measure = 0.90;
NB classification accuracy = 93.6%, sensitivity = 100%, specificity = 87.9% and f
measure = 0.95. In conclusion, SL could be a promising method for diagnosing
depression. The findings could be generalized to develop a robust CAD-based tool
that may help for clinical purposes.
PMID- 28702812
TI - Characterisation of human AV-nodal properties using a network model.
AB - Characterisation of the AV-node is an important step in determining the optimal
form of treatment for supraventricular tachycardias. To integrate and analyse
patient-specific measurements, mathematical modelling has emerged as a valuable
tool. Here we present a model of the human AV-node, consisting of a series of
interacting nodes, each with separate dynamics in refractory time and conduction
delay. The model is evaluated in several scenarios, including atrial fibrillation
(AF) and clinical pacing, using simulated and measured data. The model is able to
replicate signals derived from clinical ECG data as well as from invasive
measurements, both under AF and pacing. To quantify the uncertainty in parameter
estimation, 1000 parameter sets were sampled, showing that model output similar
to data corresponds to limited regions in the model parameter space. The model is
the first human AV-node model to capture both spatial and temporal dynamics while
being efficient enough to allow interactive use on clinical timescales, as well
as parameter estimation and uncertainty quantification. As such, it fills a new
niche in the current set of published models and forms a valuable tool for both
understanding and clinical research.
PMID- 28702813
TI - Dynamic factors involved in common peroneal nerve entrapment neuropathy.
AB - BACKGROUND: Common peroneal nerve (CPN) entrapment neuropathy (CPNEN) is the most
common peripheral neuropathy of the lower extremities. The pathological
mechanisms underlying CPNEN remain unclear. We sought to identify dynamic factors
involved in CPNEN by directly measuring the CPN pressure during stepwise CPNEN
surgery. METHODS: We enrolled seven patients whose CPNEN improved significantly
after CPN neurolysis. All suffered intermittent claudication, and the repetitive
plantar flexion test, used as a CPNEN provocation test, was positive. During
decompression surgery we directly measured the CPN pressure during several
decompression steps. RESULTS: Before CPN decompression, plantar flexion elicited
a statistically significant increase in the CPN pressure (from 1.8 to 37.3, p <
0.05), as did plantar extension (from 1.8 to 23.1, p < 0.05). The CPN pressure
gradually decreased during step-by-step surgery; it was lowest after resection of
the peroneus longus muscle (PLM) fascia. CONCLUSIONS: Dynamic factors affect
idiopathic CPNEN. The CPN pressure decreased at each surgical decompression step,
and removal of the PLM fascia resulted in adequate decompression of the CPN. Our
findings shed light on the etiology of idiopathic CPNEN and recommend adequate
CPNEN decompression procedures.
PMID- 28702814
TI - Evaluating the impact of varied compliance to lung cancer screening
recommendations using a microsimulation model.
AB - BACKGROUND: The US preventive services task force (USPSTF) recently recommended
that individuals aged 55-80 with heavy smoking history be annually screened by
low-dose computed tomography (LDCT), thereby extending the stopping age from 74
to 80 compared to the national lung screening trial (NLST) entry criterion. This
decision was made partly with model-based analyses from cancer intervention and
surveillance modeling network (CISNET), which assumed perfect compliance to
screening. METHODS: As part of CISNET, we developed a microsimulation model for
lung cancer (LC) screening and calibrated and validated it using data from NLST
and the prostate, lung, colorectal, and ovarian cancer screening trial (PLCO),
respectively. We evaluated population-level outcomes of the lifetime screening
program recommended by the USPSTF by varying screening compliance levels.
RESULTS: Validation using PLCO shows that our model reproduces observed PLCO
outcomes, predicting 884 LC cases [Expected(E)/Observed(O) = 0.99; CI 0.92-1.06]
and 563 LC deaths (E/O = 0.94 CI 0.87-1.03) in the screening arm that has an
average compliance rate of 87.9% over four annual screening rounds. We predict
that perfect compliance to the USPSTF recommendation saves 501 LC deaths per
100,000 persons in the 1950 U.S. birth cohort; however, assuming that compliance
behaviors extrapolated and varied from PLCO reduces the number of LC deaths
avoided to 258, 230, and 175 as the average compliance rate over 26 annual
screening rounds changes from 100 to 46, 39, and 29%, respectively. CONCLUSION:
The implementation of the USPSTF recommendation is expected to contribute to a
reduction in LC deaths, but the magnitude of the reduction will likely be heavily
influenced by screening compliance.
PMID- 28702815
TI - Exploring Factors Influencing Childhood Obesity Prevention Among Migrant
Communities in Victoria, Australia: A Qualitative Study.
AB - Despite the availability of numerous obesity prevention initiatives in developed
countries including Australia, rising childhood obesity levels have been found
among migrant communities which contribute to widening obesity-related
disparities in these countries. We sought to understand the factors influencing
the participation of migrant communities in childhood obesity prevention
initiatives. We conducted a qualitative study using semi-structured interviews
among 48 migrant parents from African, Middle Eastern, Indian and Vietnamese
origins living in disadvantaged areas of Victoria, Australia to explore their
views on childhood obesity and its prevention. Thematic analysis showed low
obesity literacy among migrant communities, cultural influences negatively
impacting their healthy lifestyle behaviours and cultural, family-level and
community-level barriers impacting their participation in childhood obesity
prevention initiatives. There is an urgent need to improve obesity literacy among
migrant communities using bicultural workers in order to improve their
responsiveness to childhood obesity prevention initiatives. Health
interventionists are urged to incorporate culturally-mediated influences in the
design of obesity prevention programs to achieve energy balance and maintain
healthy weight among migrants. Such culturally appropriate approaches have the
potential of reducing the widening ethnic-related obesity disparities in
Australia.
PMID- 28702816
TI - Enhancing the Solubility of Fenofibrate by Nanocrystal Formation and
Encapsulation.
AB - Development of techniques to enhance bioavailability of drugs having poor water
solubility is a big challenge for pharmaceutical industry. Solubility can be
enhanced by particle size reduction and encapsulation using hydrophilic polymers.
Fenofibrate (FF) is a drug for regulating lipids. Multi-fold enhancement in
solubility of FF has been achieved by nanocrystal formation in the present study.
Nanoparticles were prepared by an evaporation-assisted solvent-antisolvent
interaction (EASAI) approach. Water-soluble polymers, viz. polyvinylpyrrolidone
(PVP), polyvinyl alcohol (PVA), and hydroxypropyl methylcellulose (HPMC), were
used to encapsulate and thus control the particle size of FF nanocrystals.
Spherical particles having average particle size well below 30 nm could be
prepared under optimum conditions. Almost complete release of the drug molecules
from the polymer-stabilized nanocrystals within 2 h was clearly evident from the
in vitro drug release studies. Infrared (FTIR) spectroscopy indicated the absence
of solvent impurities and any strong interaction between the drug and
stabilizers. The polymorphic form of raw-FF was retained in the nanoparticles as
per the X-ray diffraction (XRD) patterns. Lower crystallinity of the
nanoformulated samples compared to raw-FF was confirmed by differential scanning
calorimetric (DSC) studies.
PMID- 28702817
TI - Tamibarotene-Loaded PLGA Microspheres for Intratumoral Injection Administration:
Preparation and Evaluation.
AB - Tamibarotene (Am80) has good curative effect on advanced hepatocellular carcinoma
(HCC). To improve the therapeutic efficacy furtherly, we prepared tamibarotene
loaded PLGA microspheres (Am80-PLGA-MS) for intratumoral injection. Firstly, Am80
PLGA-MS were prepared by emulsion-solvent evaporation method. Subsequently,
microspheres were characterized by particle size analysis, drug loading (DL), and
entrapment efficiency (EE). Finally, the drug release characteristics in vitro,
pharmacokinetic, and pharmacodynamics were studied separately. According to
results obtained, microspheres were spherical with a uniform particle size 7.04
+/- 0.03 MUm and its EE and DL were 82.23 +/- 0.74 and 11.74 +/- 0.11%,
respectively. In vitro, Am80-PLGA-MS can release drug for 14 days and its release
behavior was fitted with the Higuchi equation. In pharmacokinetic studies, the
t1/2beta, MRT, and AUC of microspheres were 15.43-fold, 8.62-fold, and 9.98-fold
those of Am80 solution, respectively, which revealed that the utilization of drug
was improved obviously. The pharmacodynamics studies showed that the tumor
doubling time, growth inhibition rate, and specific growth rate of tumor of Am80
PLGA-MS were 1.34 times, 2.63 times, and 0.72 times those of drug solution,
respectively, indicating that the inhibitory effect on tumor by the microspheres
was significantly improved. In summary, Am80-PLGA-MS are promising carrier to
enhance the inhibitory effect on tumor, which will provide significantly clinical
value for treatment of HCC.
PMID- 28702818
TI - The effect of virtual endoscopy on diagnostic accuracy and airway management
strategies in patients with head and neck pathology: a prospective cohort study.
AB - PURPOSE: There is growing evidence to suggest a deficiency in anesthesiologists'
diagnosis of airway pathology and subsequent airway management planning, and
conventional instruments have not shown increases in safety. Virtual endoscopy
(VE) is a tool that can detail intraluminal anatomical "fly-through" information
in a format visually similar to the flexible endoscopic views familiar to
anesthesiologists. We aimed to determine the effect of VE on diagnostic accuracy
and airway management strategies when compared with conventional tools. METHODS:
Clinical scenarios, along with computerized tomography (CT) imaging, were
presented to 20 anesthesiologists, and structured questions were asked regarding
diagnosis of airway pathology and airway management strategy. Virtual endoscopy
videos were then provided and the questions were repeated. Following the CT and
VE presentations, the anesthesiologists' responses involving diagnostic accuracy
and airway management strategy were compared between the CT and VE techniques.
Answers relating to the utility of VE were also sought. RESULTS: Diagnostic
accuracy was 54.1% with CT alone and increased to 67.7% when VE was added (P =
0.007). In 48% of cases, the addition of VE to clinical history and CT led to
changes in airway management strategy (P < 0.001), and 90.6% of these changes
were deemed more cautious (P < 0.001). CONCLUSION: Virtual endoscopy improves the
accuracy in diagnosis of airway pathology when compared with CT alone.
Furthermore, it leads to more conservative and potentially safer airway
management strategies in patients with head and neck pathology.
PMID- 28702819
TI - Strategies for prevention of spinal-associated hypotension during Cesarean
delivery: Are we paying attention?
PMID- 28702820
TI - Patient retention and satisfaction with information exchange concerning
peripheral nerve block risks.
PMID- 28702822
TI - ?
PMID- 28702821
TI - [Bilateral cochlear implants].
AB - Cochlear implants (CI) are standard for the hearing rehabilitation of severe to
profound deafness. Nowadays, if bilaterally indicated, bilateral implantation is
usually recommended (in accordance with German guidelines). Bilateral
implantation enables better speech discrimination in quiet and in noise, and
restores directional and spatial hearing. Children with bilateral CI are able to
undergo hearing-based hearing and speech development. Within the scope of their
individual possibilities, bilaterally implanted children develop faster than
children with unilateral CI and attain, e.g., a larger vocabulary within a
certain time interval. Only bilateral implantation allows "binaural hearing,"
with all the benefits that people with normal hearing profit from, namely: better
speech discrimination in quiet and in noise, as well as directional and spatial
hearing. Naturally, the developments take time. Binaural CI users benefit from
the same effects as normal hearing persons: head shadow effect, squelch effect,
and summation and redundancy effects. Sequential CI fitting is not necessarily
disadvantageous-both simultaneously and sequentially fitted patients benefit in a
similar way. For children, earliest possible fitting and shortest possible
interval between the two surgeries seems to positively influence the outcome if
bilateral CI are indicated.
PMID- 28702823
TI - Etoposide and doxorubicin enhance the sensitivity of triple negative breast
cancers through modulation of TRAIL-DR5 axis.
AB - Death receptor 5 (DR5) is an important target for development of anticancer
agents against triple-negative breast cancer (TNBC). Recently, we reported the
molecular level details for the modulation of TRAIL-DR5 axis by quinacrine (QC)
in breast cancer cells. In this work, the DR5 mediated anticancer potential of
topoisomerase inhibitor etoposide (ET) and doxorubicin (DOX) against TNBC has
been evaluated. ET and DOX enhanced the DR5 expression in TNBC cells, whereas non
topoisomerase inhibitors pifithrin-alpha (PIF) and dexamethasone (DEX) failed to
do so. In the TRAIL pre-treated cells, ET and DOX induced higher apoptosis,
indicating their synergistic effect with TRAIL. The molecular docking and
molecular dynamics studies showed their ability to stabilize the TRAIL-DR5
complex, whereas PIF and DEX failed to do so. The binding energy for TRAIL-DR5
complexation in the ternary complexes containing ET (-111.08 kcal/mol) and DOX (
76.35 kcal/mol) were higher than reported binding energy of binary complex (
53.70 kcal/mol). The in silico and in vitro mutational studies highlighted the
importance of DR5 residue SerB68 in mediating the receptor-drug interaction. ET
and DOX failed to enhance apoptosis in DR5 knockdown (DR5-KD) cells. On the other
hand, TRAIL+ET exhibited induction of DR5 and subsequent apoptosis in WT-DR5
overexpressed DR5-KD cells, by modulating the mitochondrial intrinsic apoptosis
cascade. An induction of apoptosis and DR5 expression was noticed in xenograft
mice and in TNBC patient-derived metastatic cells after TRAIL+ET treatment. Thus,
data suggests ET and DOX act as DR5 agonistic ligands and enhance the cellular
apoptosis in TNBC.
PMID- 28702824
TI - Optimal timing of renal replacement therapy in patients with acute kidney injury
in the context of sepsis : Discussion on "Sepsis: frontiers in supportive care,
organisation and research".
PMID- 28702825
TI - Olfactory dysfunction and quality of life in patients with transfusion-dependent
thalassemia.
AB - Transfusion-dependent thalassemia (TDT) is a group of thalassemia syndromes that
require regular blood transfusions for survival. It is unknown whether the sense
of smell of patients with TDT is affected, and if so, whether smell loss has an
adverse effect on quality of life (QOL). Olfactory thresholds were measured using
Snap & Sniff(r) wands. QOL was assessed via the Short Form-36 (SF-36)
questionnaire. Forty-two TDT patients from the Thalassemia Center in Istanbul
Medical Faculty were tested (mean age 26.6 years), along with 42 healthy controls
(mean age 28.0 years). Mean olfactory sensitivity was lower in the TDT patients
than the controls (p < 0.0001). TDT was associated with lower mean QOL scores on
the domains of physical function (p < 0.0001), physical role limitation (p =
0.011), and general health (p < 0.0001). Within the TDT group, significant
correlations were present between the threshold scores and physical function,
physical role limitation, emotional role limitation, and general health. Patients
with TDT are less sensitive to odors than healthy controls and the lower
olfactory test scores are related to lower quality of life, suggesting that
decreased smell function is an additional complication of this disease.
PMID- 28702826
TI - Head and neck diffuse large B cell lymphomas (HN-DLBCL) in human immunodeficiency
virus (HIV) positive patients: long-term results in the highly active
antiretroviral therapy (HAART) era.
AB - To report long-term outcomes and toxicity rates after chemotherapy (CHT) followed
by radiotherapy (RT) in the highly active antiretroviral therapy (HAART) era in
human immunodeficiency virus (HIV) positive patients with head and neck diffuse
large B cell lymphomas (HN-DLBCL). Clinical data concerning consecutive HIV
patients treated for DLBCL located in head and neck region with CHT and RT were
retrospectively reviewed. Systemic treatment consisted of combination CHT agents
given with concomitant HAART and regimen was left to oncologists' discretion.
Involved field RT was delivered at a total dose of 30-36 Gy (2 Gy per fraction).
Survival rates were estimated using the Kaplan-Meier method. Toxicity was
evaluated using National Cancer Institute's Common Terminology Criteria for
Adverse Events. Overall, 13 patients were included. There were no missing data.
Eight patients had advanced disease (stage III-IV = 8; 61.5%). The most common
primary tumor location was oral cavity (n = 7) with large mass at presentation.
All patients completed the programmed treatment. Severe acute toxicity was
observed in one patient, only. Overall, three patients had died and no treatment
related deaths occurred. After a median follow-up of 152 months, the 20-year
overall survival and disease-free survival rates were 65.9 and 41.5%,
respectively. Globally, there were no RT-related late complications. This data
analysis suggested that CHT followed by RT can be safety proposed in the
management of patients with HIV-related HN-DLBCL in the HAART era. Further
investigations are necessary to validate our results.
PMID- 28702827
TI - A case of atrial cardiomyopathy in a patient with rheumatic heart disease with
massive left atrial calcification.
PMID- 28702828
TI - Evaluating the perioperative safety of laparoscopic radical nephrectomy for
large, non-metastatic renal tumours: a comparative analysis of T1-T2 with T3a
tumours.
AB - OBJECTIVE: With increasing surgeon experience, the use of laparoscopic radical
nephrectomy (LRN) in large and locally advanced renal tumours (T3a) is gaining
favour in urological practice. There are limited studies reporting surgical
outcomes in such groups. The aim of this study was to review our experience with
LRN in these patients. METHODS: Data was retrospectively collected on 201
consecutive patients who underwent LRN for renal cancer by a single surgeon.
Perioperative parameters assessed were age, gender, American Society of
Anaesthesiologists score (ASA), waist circumference, tumour size, specimen size,
histological subtypes, anaesthetic duration, operative approach and technique,
surgery duration, blood loss, pre and postoperative renal function, complication
rate and duration of hospital stay. RESULTS: Of 201 patients undergoing LRN, 43
(21%) patients had T3a tumours (group 2). The remaining 158 (79%) patients had T1
tumours (group1). Mean tumour size in group 2 was 12.2 cm. Renal cell carcinoma
(RCC) was more common in males than females (131/201; 65%). Patients with T3a
disease were more likely to have an ASA score of 2 (37/201; 18%). In the majority
of patients across both groups, LRN was completed using a 3-port approach
(173/201; 86%). There were no significant differences between groups in terms of
mean anaesthetic duration, average surgical time, average estimated blood loss,
complication rate and mean hospital stay. CONCLUSION: Our study shows that LRN
has equivalent perioperative outcomes and safety in larger and locally advanced
renal tumours.
PMID- 28702829
TI - Severe obstructive sleep apnea treatment with oral appliance: the impact on
obstructive, central and mixed events.
AB - PURPOSE: The aim of this study is to evaluate the effectiveness of two types of
oral appliance (OA) in the treatment of severe obstructive sleep apnea syndrome
(OSAS) and their impact on the reduction of obstructive, central and mixed
apneas. METHODS: Forty-eight patients suffering from severe OSAS with a history
of non-adherence to positive airway pressure therapy were treated with OA
(lingual orthosis and combined orthosis). Polysomnography exams were performed
before and after treatment. Computed tomography and cephalometric radiography
were requested for all patients to evaluate the titrated position of the OA and
the airspace obtained. Statistical tests used the Minitab, version 17, program.
The level of statistical significance was 5%. RESULTS: Before treatment, the mean
AHI was 56.3 +/- 19.1 events/h. It decreased to 8.1 +/- 5.2 after the OA
titration (p <= 0.001). There was a significant reduction in obstructive events
from 43.0 +/- 20.2 to 7.1 +/- 4.6 events/h (p <= 0.001). The reduction in central
events after OA treatment was also significant (from 5.1 +/- 9.3 to 0.8 +/- 1.9
events/h; p <= 0.001), whereas that in mixed events decreased from 6.4 +/- 9.5 to
0.1 +/- 0.3 events/h (p <= 0.001). The minimum oxygen saturation also showed
significant improvement after treatment (p <= 0.001). There was no statistically
significant difference between both OA with respect to central events (p = 0.22)
or mixed events (p = 0.98). CONCLUSION: The treatment was effective in reducing
obstructive events which were evaluated through the AHI and minimum oxygen
saturation. The oral appliances also normalized central and mixed events among
patients with severe OSAS.
PMID- 28702830
TI - Sleep-disordered breathing in patients with neuromuscular disease.
AB - Sleep-disordered breathing (SDB) is relatively common in general population as
well as in patients with neuromuscular disease. SDB comprises a wide spectrum of
disorders varying from simple snoring to complete closure of the upper airway as
seen in obstructive sleep apnoea (OSA). It includes also other disorders like
prolonged hypoxemia, hypoventilation, and central sleep apnoea (CSA).
Neuromuscular diseases (NMD) form a group of disorders that can cause significant
reduction in the quality and span of life. The involvement of respiratory system
in the context of these disorders is the most serious complication, and it is
considered as the leading cause of death in those patients. NMD can affect
ventilation, cough, swallowing, and phonation. The involvement of respiratory
muscles makes NMD patients vulnerable to sleep-disordered breathing with a
significant prevalence of SDB among such patients.
PMID- 28702831
TI - Mitteilungen der DGKFO.
PMID- 28702832
TI - Effect of Perfusion on Diffusion Kurtosis Imaging Estimates for In Vivo
Assessment of Integrated 2016 WHO Glioma Grades : A Cross-Sectional Observational
Study.
AB - PURPOSE: To assess the role of perfusion-related signal decay on diffusion
kurtosis imaging (DKI) estimates for in vivo stratification of glioma according
to the integrated approach of the 2016 World Health Organization classification
of tumors of the central nervous system (2016 CNS WHO). METHODS: In this study 77
patients with histopathologically confirmed glioma were retrospectively assessed
between January 2013 and February 2017 in a prospective trial. Mean kurtosis (MK)
and mean diffusivity (MD) metrics from DKI were assessed by two physicians
blinded to the study from a volume of interest around the entire solid tumor.
Wilcoxon's signed-rank test compared perfusion-biased and perfusion-corrected MK
(MKpb and MKpc) and MD (MDpb, MDpc) values. One-way ANOVA was used to compare
MKpb&pc and MDpb&pc values between 2016 WHO glioma grades. Spearman's correlation
coefficient was used to correlate them with 2016 WHO glioma grades. Receiver
operating characteristic (ROC) analysis was performed on MKpb&pc and MDpb&pc for
the significant results. RESULTS: The MKpc values were significantly higher than
MKpb values (p < 0.001), whereas MDpc values were significantly lower than MDpb
values (p < 0.001). For stratifying gliomas, MKpb values (ROC AUC range, 0.818
0.979) showed a higher diagnostic performance than MKpc values (ROC AUC range,
0.773-0.975), whereas MDpb values (ROC AUC range, 0.744-0.928) showed less
diagnostic performance than MDpc values (ROC AUC range, 0.753-0.934). The
diagnostic accuracy of MKpb was 80.0%. CONCLUSION: The MK and MD estimates of DKI
are influenced by microcapillary blood perfusion; however, taking the effect of
perfusion on DKI metrics into account does not substantially impact their overall
diagnostic performance in classifying glioma according to the 2016 CNS WHO.
PMID- 28702833
TI - Comment on "Collaborative Training Efforts with Pediatric Providers in Addressing
Mental Health Problems in Primary Care".
PMID- 28702834
TI - The recalibration of tactile perception during tool use is body-part specific.
AB - Two decades of research have demonstrated that using a tool modulates spatial
representations of the body. Whether this embodiment is specific to
representations of the tool-using limb or extends to representations of other
body parts has received little attention. Several studies of other perceptual
phenomena have found that modulations to the primary somatosensory representation
of the hand transfers to the face, due in part to their close proximity in
primary somatosensory cortex. In the present study, we investigated whether tool
induced recalibration of tactile perception on the hand transfers to the cheek.
Participants verbally estimated the distance between two tactile points applied
to either their hand or face, before and after using a hand-shaped tool. Tool use
recalibrated tactile distance perception on the hand-in line with previous
findings-but left perception on the cheek unchanged. This finding provides
support for the idea that embodiment is body-part specific. Furthermore, it
suggests that tool-induced perceptual recalibration occurs at a level of
somatosensory processing, where representations of the hand and face have become
functionally disentangled.
PMID- 28702835
TI - Early response activation in repetition priming: an LRP study.
AB - According to recent interpretations of repetition priming, response codes are
automatically bound to a stimulus and retrieved during successive presentations
of the stimulus, hence, affecting its current processing. Despite a solid corpus
of behavioural evidence in line with this interpretation, electrophysiological
studies have reported contrasting results regarding the nature and the timing of
response code retrieval. The present experiment aims to establish at which stage
of information processing decision and action codes are retrieved in repetition
priming. To this end, the lateralized readiness potential (LRP) was analysed for
primed faces to monitor motor cortex activity related to response preparation.
Congruent and incongruent responses were obtained by having identical or reversed
tasks between study and test. Primed stimuli presented LRP activations with
opposite polarities for the two congruency conditions in the time-window 250-300
ms, indicating response-related motor cortex activity resulting from the
retrieval of correct and incorrect decision/action codes for congruent and
incongruent trials, respectively. This result indicates that decision and action
codes bound to a primed stimulus are retrieved at early stages of stimulus
processing and that these codes are transmitted to the motor cortex.
PMID- 28702836
TI - Sequential language learning and language immersion in bilingualism: diffusion
MRI connectometry reveals microstructural evidence.
AB - Study of bilingual brain has provided evidence for probable advantageous outcomes
of early second language learning and brain structural correlates to these
outcomes. DMRI connectometry is a novel approach that tracts fibers based on
correlation of the adjacent voxels with a variable of interest or group
differences. Using the data deposited by Pliatsikas et al., we investigated
through diffusion MRI connectometry and correlation analysis, the structural
differences in white matter tracts of 20 healthy sequential bilingual adults who
used English as a second language on a daily basis, compared to 25 age matched in
fiber differentiation analyses. Connectometry results revealed increased
connectivity in corpus callosum (CC), bilateral cingulum, arcuate fasciculus
(AF), and left IFOF of sequential bilingual adults. All the above fibers except
cingulum had positive association with language immersion period. We introduce
cingulum as a tract with increased connectivity in late bilingual adults. We also
found an increase in white matter connectivity conventional language-related
fibers such as AF, and areas that had been shown in previous studies addressing
WM differences between early or late bilinguals and monolinguals, inferior
frontooccipital fasciculus, and CC. Pliatsikas reported a confounding effect for
the immersion period, as a regressor in TBSS model. Through DMRI connectometry
and correlation analysis, we showed that quantitative anisotropy of all of the
significant fibers from connectometry analysis, except cingulum, had direct
correlation with the duration of immersion period of the bilingual group into the
second language.
PMID- 28702837
TI - [Compression or expansion of morbidity in outpatient healthcare? : Generation
65plus in 2007 and 2014].
AB - BACKGROUND: The ageing population raises the question whether there is a
compression or expansion of morbidity. OBJECTIVE: This study examined the
development of morbidity and the associated outpatient volume of services in
outpatient healthcare. MATERIAL AND METHODS: With a nationwide sample of
statutory health insurance patients, the development of the documented morbidity
and outpatient volume of services of the generation 65plus was empirically
examined by a retrospective, cohort-specific study based on outpatient claims
data covering the years 2007 and 2014. RESULTS: In 2014 the proportion of
multimorbid patients was increased compared to chronically ill patients, other
users and non-users. A subgroup analysis showed declining incidences for nearly
all age and gender groups. In total, the average outpatient volume of services
per patient increased, which is primarily attributable to increasing care of
multimorbid and deceased patients. CONCLUSION: High life expectancy leads to a
susceptibility for chronic diseases and multimorbidity, which indicates an
expansion of morbidity in outpatient care. The resulting increased need for
outpatient care should be covered with specific healthcare concepts for
chronically ill and multimorbid patients. Declining incidences are a positive
indication to reinforce health-promoting measures for the generation 65plus. To
develop specific healthcare offers for a heterogeneous generation 65plus, a
differentiated analysis for example by socioeconomic status and disease patterns
is needed.
PMID- 28702838
TI - In-person and online social participation and emotional health in individuals
with multiple sclerosis.
AB - PURPOSE: Individuals with multiple sclerosis (MS) sometimes have barriers to
social participation. The advent of the internet has created online support
systems for social participation such as websites for individuals with MS.
However, minimal research has been conducted about determinants of individuals'
in-person and online social participation or how types of social participation
contribute to emotional well-being. The present study aims are: (1) to assess the
role of access to resources and other determinants as enabling in-person and
online social participation, and (2) to analyze the association between social
participation and emotional health of individuals with MS. METHODS: The sample
consisted of 508 individuals diagnosed with relapsing/remitting or
secondary/progressive MS. Data from NARCOMS registry and data from original
questionnaire on determinants of social participation and emotional health were
merged. Logistic and linear regression analyses were performed. RESULTS:
Individuals with access to the internet were more likely to participate online
with friends (OR 5.47, p < .001) and the community (OR 47.7, p < .001).
Individuals who regularly participate in in-person social participation with
friends reported being happier (B = .38, p < .001), less depressed (B = -2.01, p
< .001), and less anxious (B = -1.21, p < .001) than those who did not. However,
there was no evidence of a relationship between emotional health and online
social participation. CONCLUSION: Increasing access to in-person social
participation with friends will likely have the most positive impact on emotional
health. Future research should examine the aspects of online participation that
are helpful or harmful.
PMID- 28702839
TI - Macroscopic and stereomicroscopic comparison of hacking trauma of bones before
and after carbonization.
AB - This experimental study examined lesions produced by a hatchet on pig femurs
before and after carbonization. A total of 30 lesions were produced and analyzed
using stereomicroscopy and then reexamined after carbonization. Not only was the
sharp-blunt mechanism of the hacking trauma (V-shape, regularity of one edge,
irregularity of the other edge, upraising, lateral pushing back, fossae dug
laterally to the edge) still recognizable after carbonization; in some instances,
the carbonization actually enhanced the features observed. Carbonization also did
not significantly alter the measurements of the lesions. Carbonization tends to
alter the structure of the bone especially in areas weakened by the blunt trauma.
PMID- 28702840
TI - Oncolytic viruses: adenoviruses.
AB - Tumor-selectively replicating (oncolytic) viruses are promising tools for therapy
of solid cancers and have been initially developed to achieve potent tumor lysis
with acceptable side effects on healthy tissue. However, in recent years,
oncolytic viruses have been recognized as therapeutic vehicles exhibiting
multipronged anti-tumoral activity. Apart from direct cytolysis, stimulation of
both innate and adaptive tumor-directed immune responses have been recognized as
important mechanisms of oncolytic virotherapy, which were probably decisive in
achieving the long-term tumor remissions that oncolytic viruses have shown in
clinical trials in advanced melanoma. In this short review, we will introduce
basic mechanisms of viral oncolysis and the current state of clinical
development. With a focus on oncolytic adenoviruses, we will describe the efforts
to restrict oncolytic virus infection to tumor tissue using conditional
replication and targeted delivery. Furthermore, we will discuss ways to optimize
virus-mediated immunostimulation and the potential of virotherapy as an
integrative part of systemic tumor immunotherapies.
PMID- 28702841
TI - Comparison of ketamine and ketofol for deep sedation and analgesia in children
undergoing laser procedure.
AB - The aim of our study was to research and evaluate cardiovascular and respiratory
stability, clinical efficacy, and safety of two different anesthetic agents in
pediatric patients who underwent Pulse dye (wavelength 595 nm, pulse duration 0
40 ms, power 0-40 J) and CO2 (wavelength 10,600 nm, intensity-fraxel mod with SX
index 4 to 8, power 0-30 W) laser procedure. This prospective non-blinded study
included 203 pediatric patients ASA I-II, aged between 1 month and 12 years who
underwent short-term procedural sedation and analgesia for the laser procedure.
After oral premedication with midazolam, 103 children were analgo-sedated with
ketamine and fentanyl (K group) and 100 with ketofol and fentanyl (KT group).
Vital signs, applied drug doses, pulse oximetry, and parental satisfaction
questionnaire were used to compare these two groups. Statistical differences were
tested using Student's t test, Mann-Whitney U test, chi-square test, and Fisher's
exact test. Receiver operating characteristic (ROC) curve analysis was used to
assess the cut-off value of the duration of anesthesia predicting apnea.
Tachycardia was recorded in a significantly higher number of patients who
received ketamine as the anesthetic agent (35.9 vs. 3% respectively).
Hypertension was also significantly more frequent in patients who received
ketamine in comparison with patients who received ketofol (25.2 vs. 3%).
Laryngospasm was not observed in both examined groups. There was no statistically
significant difference between groups in satisfaction of parents and doctors.
Apnea and respiratory depression occurred significantly more frequent in ketofol
than in ketamine group (12 vs. 0.97% and 13 vs. 0%). Based on ROC analysis for
apnea, we found a significantly higher number of patients with apnea in the
ketofol group when duration of anesthesia was longer than 17 min. Our study has
shown that ketofol is more comfortable than ketamine in short-term laser
procedures in children, causing less hemodynamic alteration with mild respiratory
depression and less post-procedural adverse events.
PMID- 28702842
TI - Essential role of SH3GL1 in interleukin-6(IL-6)- and vascular endothelial growth
factor (VEGF)-triggered p130cas-mediated proliferation and migration of
osteosarcoma cells.
AB - We recently demonstrated that interleukin-6 (IL-6)- and vascular endothelial
growth factor (VEGF)-induced osteosarcoma (OS) cell proliferation and migration
are parallel to significant increased expression of SH3GL1 and the
phosphorylation level of P130cas. The expression level of SH3GL1 was widely
upregulated in human OS tissues, and their overexpression was significantly
correlated with more aggressive clinicopathological features. Conversely,
depletion of SH3GL1 by adenovirus shRNA abrogates P130cas phosphorylation and IL
6- and VEGF-induced OS cell proliferation and migration. To further pinpoint the
mechanism how SH3GL1 was responsible for cell proliferation and migration, we
deleted SH3GL1 in vitro and in vivo. In vitro, depletion of SH3GL1 abrogates
P130cas phosphorylation and IL-6- and VEGF-induced OS cell proliferation and
migration. SH3GL1 knockdown caused cell cycle arrest in G0/G1 phase via
downregulation of cyclin D1, caused activation of p27KIP, and attenuated the
activation of p-Rb. Interestingly, SH3GL1 knockdown also markedly attenuated the
phosphorylation level of Akt/GSK-3beta/FAK. In vivo, depletion of SH3GL1 by shRNA
inhibited the tumor tissue growth and the expression of p-P130cas. Collectively,
our results strongly suggest that SH3GL1 is a novel target for anti-osteosarcoma.
PMID- 28702843
TI - Cytoreductive nephrectomy in patients with metastatic renal cell carcinoma in the
era of targeted therapy: a bibliographic review.
AB - PURPOSE: To evaluate the role of cytoreductive nephrectomy (CN) in metastatic
renal cell carcinoma (mRCC), against a background of lack of evidence following
the introduction of targeted therapy. METHODS: A literature review was performed
in January 2017 using the MEDLINE/PubMed and EMBASE databases. The PRISMA
guidelines were followed for conduct of the study. Two authors independently
screened the 270 papers retrieved from the search, and the finally selected
publications were identified by consensus between the two reviewers. A total of
55 studies were included in the present review. RESULTS: Globally, the
indications for CN have decreased over recent years. Although current guidelines
consider CN an adequate option in selected patients based on prospective studies
in the cytokine era, evidence for CN in the era of targeted therapy is based on
retrospective studies only. CONCLUSIONS: The results of ongoing prospective
studies are still awaited. Retrospective data suggest that young male patients
with oligometastatic disease and a good performance status can be considered
suitable surgical candidates who may benefit from CN.
PMID- 28702844
TI - Influence of acetylsalicylic acid and low-molecular weight heparins on the
formation of renal hematoma after shock wave lithotripsy.
AB - PURPOSE: To investigate the risk of renal hematoma (RHT) after shock wave
lithotripsy (SWL) among patients on acetylsalicylic acid (ASA) or low-molecular
weight heparin (LMWH). PATIENTS AND METHODS: Retrospective analysis of 434
patients treated with SWL for nephrolithiasis and ureterolithiasis of the
proximal ureter. Primary endpoint was detection of RHT by ultrasound the day
after SWL. Secondary outcome variables included transfusion of erythrocyte
concentrate(s), interventions, hospital readmission or death due to RHT within 30
days of SWL. Binary logistic regression analysis was used including a post hoc
one-way analysis. RESULTS: Of 434 patients, 33 (7.6%) and 67 (15.4%) patients
were medicated with ASA and LMWH, respectively. RHT was detected in 20 of 434
(4.6%) patients. Of those, 3 (20%) were on ASA, 6 (35%) were on LMWH, 1 (5%) was
on ASA and LMWH, and 10 (50%) had no anticoagulation. Univariate analysis showed
a statistically significant higher risk for RHT among patients on ASA (p = 0.04)
and LWMH (p = 0.02) with an untreated urinary tract infection (UTI) (p = 0.008)
and history of cardiovascular disease (p = 0.028). On multivariate analysis, ASA
medication, untreated UTI (OR 4.4, 95% CI 1.31-14.75, p = 0.016 and OR 5.79, 95%
CI 1.65-20.32, p = 0.03) and a therapeutic dose of LMWH (OR 10.4, 95% CI 1.74
62.27, p = 0.01) were independent predictors for RHT. CONCLUSIONS: Before SWL, a
patient risk profile should be evaluated. If feasible, LMWH in therapeutic dosing
should be avoided, and ASA should be discontinued. UTI should be treated before
SWL in any case. TRIAL REGISTRATION: http://www.clinicaltrials.gov ; Identifier
NCT02875717.
PMID- 28702845
TI - Regulation of cardiac Ca2+ and ion channels by shear mechanotransduction.
AB - Cardiac contraction is controlled by a Ca2+ signaling sequence that includes L
type Ca2+ current-gated opening of Ca2+ release channels (ryanodine receptors) in
the sarcoplasmic reticulum (SR). Local Ca2+ signaling in the atrium differs from
that in the ventricle because atrial myocytes lack transverse tubules and have
more abundant corbular SR. Myocardium is subjected to a variety of forces with
each contraction, such as stretch, shear stress, and afterload, and adapts to
those mechanical stresses. These mechanical stimuli increase in heart failure,
hypertension, and valvular heart diseases that are clinically implicated in
atrial fibrillation and stroke. In the present review, we describe distinct
responses of atrial and ventricular myocytes to shear stress and compare them
with other mechanical responses in the context of local and global Ca2+ signaling
and ion channel regulation. Recent evidence suggests that shear
mechanotransduction in cardiac myocytes involves activation of gap junction
hemichannels, purinergic signaling, and generation of mitochondrial reactive
oxygen species. Significant alterations in Ca2+ signaling and ionic currents by
shear stress may be implicated in the pathogenesis of cardiac arrhythmia and
failure.
PMID- 28702846
TI - Characterization of the encoding properties of intraspinal mechanosensory neurons
in the lamprey.
AB - Proprioceptive sensory inputs are an integral part of the closed-loop system of
locomotion. In the lamprey, a model organism for vertebrate locomotion, such
sensory inputs come from intraspinal mechanosensory cells called "edge cells".
These edge cells synapse directly onto interneurons in the spinal central pattern
generator (CPG) circuit and allow the CPG to adjust the motor output according to
how the body is bending. However, the encoding properties of the edge cells have
never been fully characterized. To identify these properties and better
understand edge cells' role in locomotion, we isolated spinal cords of silver
lampreys (Ichthyomyzon unicuspis) and recorded extracellularly from the lateral
tracts where edge cell axons are located. We identified cells that responded to
mechanical stimuli and used standard spike sorting algorithms to identify
separate units, then examined how the cells respond to bending rate and bending
angle. Although some cells respond to the bending angle, as was previously known,
the strongest and most common responses were to bending velocity. These encoding
properties will help us better understand how lampreys and other basal
vertebrates adapt their locomotor rhythms to different water flow patterns,
perturbations, or other unexpected changes in their environments.
PMID- 28702847
TI - Is surgery for pineal cysts safe and effective? Short review.
AB - In this short review, the authors performed a database search and summarize
current knowledge of the management of patients with pineal cysts (PCs) and
investigate the role of surgical treatment. The scientific literature on the
surgical treatment of PCs is sparse and encompasses only case series with little
over 200 operated patients combined. All included papers reported favorable
results after pineal cyst surgery with improvement of symptoms in most patients.
Microsurgical resection of PCs, preferably using the supracerebellar
infratentorial approach, could be considered as a viable treatment option in
symptomatic patients. Even patients with non-specific symptoms are reported to
improve after surgery. However, evidence offered by this literature review is
very limited and therefore our conclusions must be tempered by the restricted set
of data. For ethical reasons, a randomized controlled trial is not an acceptable
approach, and therefore patient registry could be a useful tool to identify a
subset of symptomatic patients that might benefit from pineal cyst resection.
PMID- 28702848
TI - Organic solvent exposure and depressive symptoms among licensed pesticide
applicators in the Agricultural Health Study.
AB - PURPOSE: Although organic solvents are often used in agricultural operations,
neurotoxic effects of solvent exposure have not been extensively studied among
farmers. The current analysis examined associations between questionnaire-based
metrics of organic solvent exposure and depressive symptoms among farmers.
METHODS: Results from 692 male Agricultural Health Study participants were
analyzed. Solvent type and exposure duration were assessed by questionnaire. An
"ever-use" variable and years of use categories were constructed for exposure to
gasoline, paint/lacquer thinner, petroleum distillates, and any solvent.
Depressive symptoms were ascertained with the Center for Epidemiologic Studies
Depression Scale (CES-D); scores were analyzed separately as continuous (0-60)
and dichotomous (<16 versus >=16) variables. Multivariate linear and logistic
regression models were used to estimate crude and adjusted associations between
measures of solvent exposure and CES-D score. RESULTS: Forty-one percent of the
sample reported some solvent exposure. The mean CES-D score was 6.5 (SD 6.4;
median 5; range 0-44); 92% of the sample had a score below 16. After adjusting
for covariates, statistically significant associations were observed between ever
use of any solvent, long duration of any solvent exposure, ever-use of gasoline,
ever-use of petroleum distillates, and short duration of petroleum distillate
exposure and continuous CES-D score (p < 0.05). Although nearly all associations
were positive, fewer statistically significant associations were observed between
metrics of solvent exposure and the dichotomized CES-D variable. CONCLUSIONS:
Solvent exposures were associated with depressive symptoms among farmers. Efforts
to limit exposure to organic solvents may reduce the risk of depressive symptoms
among farmers.
PMID- 28702849
TI - Synthesis of alpha-amino-1,3-dicarbonyl compounds via Ugi flow chemistry
reaction: access to functionalized 1,2,3-triazoles.
AB - The Ugi multicomponent reaction has been used as an important synthetic route to
obtain compounds with potential biological activity. We present the rapid and
efficient synthesis of [Formula: see text]-amino-1,3-dicarbonyl compounds in
moderate to good yields via Ugi flow chemistry reactions performed with a
continuous flow reactor. Such [Formula: see text]-amino-1,3-dicarbonyl compounds
can act as precursors for the production of [Formula: see text]-amino acids via
hydrolysis of the ethyl ester group as well as building blocks for the synthesis
of novel compounds with the 1,2,3-triazole ring. The [Formula: see text]-amino
acid derivatives of the Ugi flow chemistry reaction products were then used for
dipeptide synthesis.
PMID- 28702850
TI - Nonmotor fluctuations: phenotypes, pathophysiology, management, and open issues.
AB - Parkinson's disease (PD) is a neurodegenerative multisystem disorder
characterized by progressive motor symptoms such as bradykinesia, tremor and
muscle rigidity. Over the course of the disease, numerous non-motor symptoms,
sometimes preceding the onset of motor symptoms, significantly impair patients'
quality of life. The significance of non-motor symptoms may outweigh the burden
through progressive motor incapacity, especially in later stages of the disease.
The advanced stage of the disease is characterized by motor complications such as
fluctuations and dyskinesias induced by the long-term application of levodopa
therapy. In recent years, it became evident that various non-motor symptoms such
as psychiatric symptoms, fatigue and pain also show fluctuations after chronic
levodopa therapy (named non-motor fluctuations or NMFs). Although NMFs have moved
into the focus of interest, current national guidelines on the treatment of PD
may refer to non-motor symptoms and their management, but do not mention NMF, and
do not contain recommendations on their management. The present article
summarizes major issues related to NMF including clinical phenomenology and
pathophysiology, and outlines a number of open issues and topics for future
research.
PMID- 28702851
TI - Sexual Partner Concurrency Among Partners Reported by MSM with Recent HIV
Infection.
AB - We examined concurrency among sexual partners reported by men who have sex with
men (MSM) with recent (acute or early) HIV infection in San Diego, California
(2002-2015). Partners overlapping in time in the past 3 months were considered
concurrent. Logistic generalized linear mixed models were used to identify
factors associated with concurrency at the partner-level. 56% (388/699) of
partners were concurrent to >=1 other partner. The odds of concurrency were
higher among partners >10 years younger than the participant (vs. within 10 years
of age) [adjusted odds ratio (AOR) = 2.22, 95% confidence interval (CI) 1.09
4.52], longer term partners (AOR per month = 1.02, 95% CI 1.01-1.03), and
partners met online (AOR = 1.56, 95% CI 0.98-2.48). Concurrency is common among
partners of recently HIV-infected MSM. Tailored HIV prevention strategies for MSM
with older partners, longer term partners, and partners met online may help
minimize the potential impact of concurrency on HIV transmission.
PMID- 28702852
TI - Pilot Test of an Integrated Sexual Risk Reduction Intervention for Women with a
History of Childhood Sexual Abuse.
AB - HIV and childhood sexual abuse (CSA) are intersecting public health problems for
women. We pilot tested an integrated sexual risk reduction intervention for women
with a history of CSA that addressed both the consequences of CSA [based on the
Traumagenic Dynamics (TD) framework] and the antecedents of sexual risk behavior
(based on the Information-Motivation-Behavioral Skills [IMB] model). Women with a
history of CSA who were attending a public STI clinic (n = 84) were randomly
assigned to a five-session integrated TD/IMB (experimental) group intervention or
to a time-matched IMB-guided sexual risk reduction (control) group intervention.
Preliminary findings indicated that women in the integrated TD/IMB intervention
reduced their average number of episodes of unprotected sex with a primary
partner, their alcohol use, and their likelihood of being in a violent
relationship, relative to women in the IMB-only group. Our findings suggest that
sexual risk reduction interventions that address both the consequences of CSA and
the antecedents of sexual risk behavior may be efficacious in reducing sexual
risk behavior among women who were sexually abused.
PMID- 28702853
TI - Condomless Anal Sex Among HIV-Positive Men Who Have Sex with Men: Biomedical
Context Matters.
AB - Data from Medical Monitoring Project was used to determine if partner type is
associated with condomless anal sex (CAS) and insertive condomless anal sex
(ICAS) among HIV-positive men who have sex with men. Participants reported HIV
status and PrEP use of up to five anal sex partners. Partner type was categorized
as HIV-positive, HIV status unknown, HIV-negative on PrEP or HIV-negative not on
PrEP. To account for correlation of multiple observations per participant,
generalized estimating equations were used to calculate adjusted prevalence
ratios and 95% confidence intervals of CAS and ICAS. Condom use during anal sex
and insertive anal sex varied based on partner type. There was a higher
prevalence of CAS and ICAS in partnerships with HIV-positive partners or HIV
negative partners on PrEP compared to HIV-negative partners not on PrEP.
PMID- 28702854
TI - Gastroesophageal Reflux Disease and Pulmonary Diseases Associated with
Aspergillosis: Is There a Connection?
AB - INTRODUCTION: We studied the relationship between GORD and allergic
bronchopulmonary aspergillosis (ABPA), chronic pulmonary aspergillosis (CPA), or
Aspergillus bronchitis. BACKGROUND: Gastroesophageal reflux disease (GORD) is
well known to initiate or exacerbate pulmonary inflammatory conditions, inducing
bronchial asthma and chronic obstructive lung disease. METHODS: We reviewed four
patients referred with elevated Aspergillus serology markers and marked pulmonary
symptoms for ABPA, CPA, and Aspergillus bronchitis, and discussed the underlying
pathophysiological relationship with GORD. Data were collected retrospectively
from medical records included age, gender, predisposing factors for ABPA, chronic
pulmonary aspergillosis, or Aspergillus bronchitis; presence of nocturnal reflux,
nausea, epigastric pain, Medical Research Council dyspnea scale score, pH
manometry data, endoscopic results (ulcers, Barrett's esophagus), treatment of
GORD [proton-pump inhibitors (PPIs), surgical operation]; history of smoking,
alcohol consumption; concomitant COPD; serological markers (anti-Aspergillus IgG,
anti-Aspergillus IgE), and antifungal treatment. RESULTS: Four patients with GORD
were studied; following PPIs administration two achieved clinical improvement.
One had ABPA, one CPA, and two had Aspergillus bronchitis; median age was 57
years [range 39-71]; males-to-females ratio was 1:3. Serological markers for
aspergillosis were: median total IgE antibodies 573 KIU/L [range 13.1-850],
median Aspergillus IgE-specific antibodies 1.2 kAU/L [range <0.4-24.7], and
median Aspergillus IgG titers 71 mg/L [range 20-119]. Aspergillus fumigatus grew
in one sputum sample. CONCLUSION: Clinicians caring for patients with
gastroesophageal reflux disease presenting with elevated Aspergillus IgG or IgE
antibodies should maintain a high index of suspicion for this association and
proceed to appropriate evaluations, including laryngoscopy and endoscopy,
initiating specific PPI-directed therapy when indicated.
PMID- 28702855
TI - N-Chlorotaurine, a Promising Future Candidate for Topical Therapy of Fungal
Infections.
AB - N-Chlorotaurine (NCT) is a mild long-lived oxidant that can be applied to
sensitive body regions as an endogenous antiseptic. Enhancement of its
microbicidal activity in the presence of proteinaceous material because of
transchlorination, a postantibiotic/postantifungal effect and antitoxic activity
renders it interesting for treatment of fungal infections, too. This is confirmed
by first case applications in skin and mucous membranes of different body sites.
Recent findings of good tolerability of inhaled NCT suggest further
investigations of this substance for treatment of bronchopulmonary diseases,
where microorganisms play a role, particularly multi-resistant ones. The
availability of a well-tolerated and effective inhaled antiseptic with anti
inflammatory properties could be a significant progress, in particular for
chronic pulmonary diseases, such as chronic obstructive pulmonary disease or
cystic fibrosis.
PMID- 28702856
TI - Dynamics of Torque Teno virus viremia could predict risk of complications after
allogeneic hematopoietic stem cell transplantation.
AB - Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an established
treatment option for several hematological diseases. However, the first year post
transplantation is often complicated by infections and graft-versus-host disease
(GVHD). Improvements in immunological monitoring could reduce such post
transplant complications. Torque Teno virus (TTV), a chronically persisting DNA
virus, is reported to be a marker for immune function in immunocompromised
patients. In the present study, the TTV kinetics were analyzed to investigate the
potential role of TTV viremia as immune-competence read-out after allo-HSCT.
Twenty-three monocentric allo-HSCT recipients were retrospectively tested for TTV
DNA in whole blood at given day post-transplant. Dynamics of TTV viremia was
analyzed with respect to episodes of non-TTV viral reactivations (CMV, EBV, and
BKPyV), acute GVHD, and recovery of immune cells. Recipients affected by
persisting viral infections and/or GVHD during the first 100 days after allo-HSCT
showed a significantly higher median TTV load at day +30 than patients with a
less complicated clinical course (p = 0.005). This was also associated with a
total lymphocyte count <5.5E+08 cells/L in this high-risk group (p = 0.039).
These findings suggest that TTV could represent an additional parameter to
identify patients at higher risk for complications in the first 100 days
following allo-HSCT. Prospective studies, including the monitoring of lymphocyte
subsets, are required to define the potential use of TTV in immunological
monitoring after allo-HSCT.
PMID- 28702858
TI - Effect of renin-angiotensin system inhibitors on mortality in heart failure with
preserved ejection fraction: a meta-analysis of observational cohort and
randomized controlled studies.
AB - Despite the high mortality rate, there is no therapy to improve survival in heart
failure with preserved ejection fraction (HFpEF). Large randomized controlled
trials (RCTs) did not show clear mortality benefit of renin-angiotensin system
(RAS) inhibitors (angiotensin-converting enzyme inhibitors or angiotensin
receptor blockers) in HFpEF. However, because of the strict enrollment criteria,
the patients who participated in these trials might represent a selected group of
patients that is poorly representative of patients treated in routine clinical
practice. In contrast, clinical characteristics of real-world patients are
similar to those of patients enrolled in observational cohort studies (OCSs).
Although many OCSs have examined the prognostic effect of RAS inhibitors in
HFpEF, the results are inconsistent due to limited power with small sample sizes
and/or inadequate adjustment for known prognostic factors. We aimed to conduct a
meta-analysis of OCSs with and those without propensity score (PS) analysis and
RCTs on the effect of RAS inhibitors on mortality in HFpEF patients. The search
of electronic databases identified 4 OCSs with PS analysis (10,164 patients), 8
OCSs without PS analysis (16,393 patients), and 3 RCTs (8001 patients). Use of
RAS inhibitors was associated with reduced mortality in the pooled analysis of
OCSs with PS analysis (RR [95% CI] = 0.90 [0.81-1.00]) and in that of OCSs
without PS analysis (0.81 [0.68-0.96]) but not in that of RCTs (0.99 [0.87
1.12]). In conclusion, the present meta-analysis suggests the potential mortality
benefit of RAS inhibitors in HFpEF, emphasizing the importance of conducting new
well-designed RCTs.
PMID- 28702857
TI - Protein kinase C and cardiac dysfunction: a review.
AB - Heart failure (HF) is a physiological state in which cardiac output is
insufficient to meet the needs of the body. It is a clinical syndrome
characterized by impaired ability of the left ventricle to either fill or eject
blood efficiently. HF is a disease of multiple aetiologies leading to progressive
cardiac dysfunction and it is the leading cause of deaths in both developed and
developing countries. HF is responsible for about 73,000 deaths in the UK each
year. In the USA, HF affects 5.8 million people and 550,000 new cases are
diagnosed annually. Cardiac remodelling (CD), which plays an important role in
pathogenesis of HF, is viewed as stress response to an index event such as
myocardial ischaemia or imposition of mechanical load leading to a series of
structural and functional changes in the viable myocardium. Protein kinase C
(PKC) isozymes are a family of serine/threonine kinases. PKC is a central enzyme
in the regulation of growth, hypertrophy, and mediators of signal transduction
pathways. In response to circulating hormones, activation of PKC triggers a
multitude of intracellular events influencing multiple physiological processes in
the heart, including heart rate, contraction, and relaxation. Recent research
implicates PKC activation in the pathophysiology of a number of cardiovascular
disease states. Few reports are available that examine PKC in normal and diseased
human hearts. This review describes the structure, functions, and distribution of
PKCs in the healthy and diseased heart with emphasis on the human heart and, also
importantly, their regulation in heart failure.
PMID- 28702859
TI - Spirulina platensis prevents high glucose-induced oxidative stress mitochondrial
damage mediated apoptosis in cardiomyoblasts.
AB - The current study was undertaken to study the effect of Spirulina platensis
(Spirulina) extract on enhanced oxidative stress during high glucose induced cell
death in H9c2 cells. H9c2 cultured under high glucose (33 mM) conditions resulted
in a noteworthy increase in oxidative stress (free radical species) accompanied
by loss of mitochondrial membrane potential, release of cytochrome c, increase in
caspase activity and pro-apoptotic protein (Bax). Spirulina extract (1 MUg/mL),
considerably inhibited increased ROS and RNS levels, reduction in cytochrome c
release, raise in mitochondrial membrane potential, decreased the over expression
of proapoptotic protein Bax and suppressed the Bax/Bcl2 ratio with induced
apoptosis without affecting cell viability. Overall results suggest that
Spirulina extract plays preventing role against enhanced oxidative stress during
high glucose induced apoptosis in cardiomyoblasts as well as related dysfunction
in H9c2 cells.
PMID- 28702861
TI - Outcomes of a Single Surgeon-Based Transanal-Total Mesorectal Excision (TATME)
for Rectal Cancer.
AB - BACKGROUND: Several studies have shown the transanal total mesorectal excision
(TATME) is emerging as a safe and effective technique for proctectomy. The
majority of these studies to date, however, is based on procedures done in
centers with teams of two surgeons working simultaneously. Few were performed by
single-surgeon teams with sizeable case load. The objective of our study was to
identify the feasibility and safety of a single-surgeon TATME. METHODS: Chart
review of prospectively collected data on 27 patients who underwent TATME at our
institution from June 2015 to September 2016 were included in this study.
Indications for TATME included mid and low rectal cancers. Only patients who
underwent surgery for neoplastic lesions were included in the study. Outcomes
assessed included mesorectal integrity, margin status, operative time,
complications, morbidity, LOS, and 30-day readmission. RESULTS: A total of 27
cases were available for inclusion. A single surgeon performed all procedures.
The average BMI was 27.2 +/- 1.3 kg/m2. The average tumor distance from anal
verge was 6.8 +/- 0.6 cm. The median operative time was 283 min. No
intraoperative complications, including injuries and conversions, occurred.
Circumferential resection margin (CRM) and distal resection margin (DRM) were R0
in 96 and 100% of patients, respectively. Mesorectal integrity was "Complete" in
67% and "Near complete" in 33% of patients. There were no incomplete specimens.
The total lymph node (LN) harvest was 26 +/- 2. The average LOS was 4 days for
75% of all patients. There were no mortalities. The overall morbidity was 33%
(9/27). There were 4/27 anastomotic leaks, one required a laparoscopic ileostomy,
one had laparoscopic drainage of an abscess, and the other two were
endoscopically washed and trans-rectal drains inserted. CONCLUSION: TATME
performed by a one-surgeon team is oncologically adequate, and it is safe and
feasible. Morbidities are comparable with existing literature data from two
surgeon teams. In addition, resection margins, mesorectal integrity, and LN
harvests are also comparable or superior to some of the existing studies.
PMID- 28702862
TI - Oregon's Coordinated Care Organizations and Their Effect on Prenatal Care
Utilization Among Medicaid Enrollees.
AB - Introduction Previous studies indicate that inadequate prenatal care is more
common among women covered by Medicaid compared with private insurance.
Increasing the proportion of pregnant women who receive early and adequate
prenatal care is a Healthy People 2020 goal. We examined the impact of the
implementation of Oregon's accountable care organizations, Coordinated Care
Organizations (CCOs), for Medicaid enrollees, on prenatal care utilization among
Oregon women of reproductive age enrolled in Medicaid. Methods Using Medicaid
eligibility data linked to unique birth records for 2011-2013, we used a pre
posttest treatment-control design that compared prenatal care utilization for
women on Medicaid before and after CCO implementation to women never enrolled in
Medicaid. Additional stratified analyses were conducted to explore differences in
the effect of CCO implementation based on rurality, race, and ethnicity. Results
After CCO implementation, mothers on Medicaid had a 13% increase in the odds of
receiving first trimester care (OR 1.13, CI 1.04, 1.23). Non-Hispanic (OR 1.20,
CI 1.09, 1.32), White (OR 1.20, CI 1.08, 1.33) and Asian (OR 2.03, CI 1.26, 3.27)
women on Medicaid were more likely to receive initial prenatal care in the first
trimester after CCO implementation and only Medicaid women in urban areas were
more likely (OR 1.14, CI 1.05, 1.25) to initiate prenatal care in the first
trimester. Conclusion Following Oregon's implementation of an innovative Medicaid
coordinated care model, we found that women on Medicaid experienced a significant
increase in receiving timely prenatal care.
PMID- 28702863
TI - Walking Together: Towards a Collaborative Model for Maternal Health Care in
Pastoralist Communities of Laikipia and Samburu, Kenya.
AB - Purpose In 2009 the Kenyan Government introduced health system reforms to address
persistently high maternal and newborn mortality including deployment of skilled
birth attendants (SBAs) to health facilities in remote areas, and proscription of
births attended by traditional birth attendants (TBAs). Despite these
initiatives, uptake of SBA services remains low and inequitably distributed. This
paper describes the development of an SBA/TBA collaborative model of maternal
health care for pastoralist communities in Laikipia and Samburu. Description A
range of approaches were used to generate a comprehensive understanding of the
maternal and child health issues affecting these pastoralist communities
including community and government consultations, creation of a booklet and film
recognising the contributions of both TBAs and SBAs that formed the basis of
subsequent discussions, and mixed methods research projects. Based on the
knowledge and understanding collectively generated by these approaches we
developed an evidence-based, locally acceptable and feasible model for SBA/TBA
collaborative care of women during pregnancy and childbirth. Assessment The
proposed collaborative care model includes: antenatal and post-natal care
delivered by both SBAs and TBAs; TBAs as birth companions who support women and
SBAs; training TBAs in recognition of birth complications, nutrition during
pregnancy and following birth, referral processes, and family planning; training
SBAs in respectful maternity care; and affordable, feasible redesign of health
facility infrastructure and services so they better meet the identified needs of
pastoralist women and their families. Conclusion The transition from births
predominantly attended by TBAs to births attended by SBAs is likely to be a
gradual one, and an interim SBA/TBA collaborative model of care has the potential
to maximise the safety of pastoralist women and babies during the transition
phase, and may even accelerate the transition itself.
PMID- 28702864
TI - Tobacco Use Prevalence and Outcomes Among Perinatal Patients Assessed Through an
"Opt-out" Cessation and Follow-Up Clinical Program.
AB - Purpose Cigarette smoking in the perinatal period is associated with costly
morbidity and mortality for mother and infant, yet many women continue to smoke
throughout their pregnancy and following delivery. This report describes tobacco
use prevalence among perinatal smokers identified through an "opt-out" inpatient
smoking cessation clinical service. Description Adult women admitted to the
peripartum, delivery, and postpartum units at a large academic hospital were
screened for tobacco use. Smokers were identified through their medical record
and referred to a bedside consult and follow-up using an interactive voice
response (IVR) system to assess smoking up to 30 days post-discharge. Assessment
Between February 2014 and March 2016, 533 (10%) current and 898 (16%) former
smokers were identified out of 5649 women admitted to the perinatal units.
Current smokers reported an average of 11 cigarettes per day for approximately 12
years. Only 10% reported having made a quit attempt in the past year. The
majority of smokers (56%) were visited by a bedside tobacco cessation counselor
during their stay and 27% were contacted through the IVR system. Those counselled
in the hospital were twice as likely (RR 1.98, CI 1.04-3.78) to be abstinent from
smoking using intent-to-treat analysis at any time during the 30 days post
discharge. Conclusions This opt-out service reached a highly nicotine-dependent
perinatal population, many of whom were receptive to the service, and it appeared
to improve abstinence rates post-discharge. Opt-out tobacco cessation services
may have a significant impact on the health outcomes of this population and their
children.
PMID- 28702865
TI - Public Health Insurance and Health Care Utilization for Children in Immigrant
Families.
AB - Objectives To estimate the impacts of public health insurance coverage on health
care utilization and unmet health care needs for children in immigrant families.
Methods We use survey data from National Health Interview Survey (NHIS) (2001
2005) linked to data from Medical Expenditures Panel Survey (MEPS) (2003-2007)
for children with siblings in families headed by at least one immigrant parent.
We use logit models with family fixed effects. Results Compared to their siblings
with public insurance, uninsured children in immigrant families have higher odds
of having no usual source of care, having no health care visits in a 2 year
period, having high Emergency Department reliance, and having unmet health care
needs. We find no statistically significant difference in the odds of having
annual well-child visits. Conclusions for practice Previous research may have
underestimated the impact of public health insurance for children in immigrant
families. Children in immigrant families would likely benefit considerably from
expansions of public health insurance eligibility to cover all children,
including children without citizenship. Immigrant families that include both
insured and uninsured children may benefit from additional referral and outreach
efforts from health care providers to ensure that uninsured children have the
same access to health care as their publicly-insured siblings.
PMID- 28702866
TI - Association of the Familial Coexistence of Child Stunting and Maternal Overweight
with Indigenous Women in Guatemala.
AB - Objectives This study investigated the association of the familial coexistence of
child stunting and maternal overweight with indigenous women in Guatemala.
Methods We selected 2388 child-mother pairs from the data set of the Living
Standards Measurement Study conducted in Guatemala in 2000. This study examined
the association between maternal and household characteristics and the
nutritional status of children aged 6-60 months and mothers aged 18-49 years by
using multivariable logistic regression models. Results Compared with non
indigenous households, a significantly higher percentage of indigenous households
exhibited stunted child and overweight mother (SCOM) pairs (15.9 vs. 22.2%).
Compared with normal-weight mothers, overweight mothers were less likely to have
stunted children [adjusted odds ratio (AOR) 0.66, 95% confidence interval (CI)
0.50-0.88]. However, compared with mothers who were not short and overweight,
short and overweight mothers were significantly more likely to have stunted
children (AOR 1.80, 95% CI 1.19-2.73) and were more likely to be indigenous women
living in urban areas (AOR 3.01, 95% CI 1.19-7.60) or rural areas (AOR 3.02, 95%
CI 1.28-7.14). The order of observed prevalence of SCOM pairs in different types
of households was as follows: urban indigenous (25.0%), rural indigenous (21.2%),
rural non-indigenous (19.8%), and urban non-indigenous households (10.7%).
Conclusions for Practice Urban indigenous households were more likely to have
SCOM pairs. This study provided useful information for identifying the most
vulnerable groups and areas with a high prevalence of the familial coexistence of
child stunting and maternal overweight.
PMID- 28702867
TI - Exercise to Support Indigenous Pregnant Women to Stop Smoking: Acceptability to
Maori.
AB - Objectives Smoking during pregnancy is harmful for the woman and the unborn
child, and the harms raise risks for the child going forward. Indigenous women
often have higher rates of smoking prevalence than non-indigenous. Exercise has
been proposed as a strategy to help pregnant smokers to quit. Maori (New Zealand
Indigenous) women have high rates of physical activity suggesting that an
exercise programme to aid quitting could be an attractive initiative. This study
explored attitudes towards an exercise programme to aid smoking cessation for
Maori pregnant women. Methods Focus groups with Maori pregnant women, and key
stakeholder interviews were conducted. Results Overall, participants were
supportive of the idea of a physical activity programme for pregnant Maori
smokers to aid smoking cessation. The principal, over-arching finding, consistent
across all participants, was the critical need for a Kaupapa Maori approach
(designed and run by Maori, for Maori people) for successful programme delivery,
whereby Maori cultural values are respected and infused throughout all aspects of
the programme. A number of practical and environmental barriers to attendance
were raised including: cost, the timing of the programme, accessibility,
transport, and childcare considerations. Conclusions A feasibility study is
needed to design an intervention following the suggestions presented in this
paper with effort given to minimising the negative impact of barriers to
attendance.
PMID- 28702868
TI - Safety and tolerability of the ketogenic diet used for the treatment of
refractory childhood epilepsy: a systematic review of published prospective
studies.
AB - BACKGROUND: To review the available evidence from prospective studies on the
safety and tolerability of the ketogenic diet (KD) for the treatment of
refractory childhood epilepsy. METHODS: A comprehensive bibliographic search was
performed with the aim of retrieving prospective studies that monitored adverse
effects (AEs) in children after receiving the classic or medium-chain
triglyceride KD therapy for refractory epilepsy. RESULTS: A total of 45 studies
were retrieved, including 7 randomized controlled trials. More than 40 categories
of AEs were reported. The most common AEs included gastrointestinal disturbances
(40.6%), hyperlipidemia (12.8%), hyperuricemia (4.4%), lethargy (4.1%),
infectious diseases (3.8%) and hypoproteinemia (3.8%). Severe AEs, such as
respiratory failure and pancreatitis, occurred in no more than 0.5% of children.
Specifically, patients receiving KD therapy should be monitored for osteopenia,
urological stones, right ventricular diastolic dysfunction, and growth
disturbance. The total retention rates of the diet for 1 year and 2 years were
45.7% and 29.2%, respectively. Nearly half of the patients discontinued the diet
because of lack of efficacy. AEs were not the main reason for the KD
discontinuation. None of the 24 deaths reported after initiation of the diet was
attributed to the KD. CONCLUSIONS: KD is a relatively safe dietary therapy.
However, because the KD can cause various AEs, it should be implemented under
careful medical supervision. Continuous follow-up is needed to address the long
term impact of the diet on the overall health of children.
PMID- 28702869
TI - Ambulatory clinical parameters and sleep respiratory events in a group of obese
children unselected for respiratory problems.
AB - BACKGROUND: Obstructive sleep apnea in children is frequently due to tonsil and
adenoid hypertrophy. This study aimed to investigate the relationship between
ambulatory clinical parameters and sleep respiratory events in obese children.
METHODS: We carried out a prospective respiratory sleep study between 2013 and
2015. Nails obstruction, tonsils enlargement and palate position were
subjectively measured. Italian attention deficit hyperactivity disorder (ADHD)
rating scale for parents was also performed. The polygraph study was performed
using a portable ambulatory device. RESULTS: Forty-four obese children were
consecutively recruited into this study. Mild sleep respiratory disturbance was
showed in 31.8 % of patients; 18.2% previously had an adeno (tonsillectomy). In
50% of these obese children, both apnea-hypopnea index and oxygen desaturation
index showed polygraph abnormal results. ADHD rating scale for parents scores
were positive in 9.1% of patients. CONCLUSIONS: We found a high rate of mild
sleep respiratory disturbance and ADHD-like symptoms referred by parents. The
respiratory disturbance was not totally cured by surgery. Finally,
otorhinolaryngology variables were not able to explain mild sleep respiratory
disturbance.
PMID- 28702870
TI - Randomized Controlled Trial of Brief Mindfulness Training and Hypnotic Suggestion
for Acute Pain Relief in the Hospital Setting.
AB - BACKGROUND: Medical management of acute pain among hospital inpatients may be
enhanced by mind-body interventions. OBJECTIVE: We hypothesized that a single,
scripted session of mindfulness training focused on acceptance of pain or
hypnotic suggestion focused on changing pain sensations through imagery would
significantly reduce acute pain intensity and unpleasantness compared to a
psychoeducation pain coping control. We also hypothesized that mindfulness and
suggestion would produce significant improvements in secondary outcomes including
relaxation, pleasant body sensations, anxiety, and desire for opioids, compared
to the control condition. METHODS: This three-arm, parallel-group randomized
controlled trial conducted at a university-based hospital examined the acute
effects of 15-min psychosocial interventions (mindfulness, hypnotic suggestion,
psychoeducation) on adult inpatients reporting "intolerable pain" or "inadequate
pain control." Participants (N = 244) were assigned to one of three intervention
conditions: mindfulness (n = 86), suggestion (n = 73), or psychoeducation (n =
85). KEY RESULTS: Participants in the mind-body interventions reported
significantly lower baseline-adjusted pain intensity post-intervention than those
assigned to psychoeducation (p < 0.001, percentage pain reduction: mindfulness =
23%, suggestion = 29%, education = 9%), and lower baseline-adjusted pain
unpleasantness (p < 0.001). Intervention conditions differed significantly with
regard to relaxation (p < 0.001), pleasurable body sensations (p = 0.001), and
desire for opioids (p = 0.015), but all three interventions were associated with
a significant reduction in anxiety (p < 0.001). CONCLUSIONS: Brief, single
session mind-body interventions delivered by hospital social workers led to
clinically significant improvements in pain and related outcomes, suggesting that
such interventions may be useful adjuncts to medical pain management. TRIAL
REGISTRATION: Trial Registry: ClinicalTrials.gov ; registration ID number:
NCT02590029 URL: https://clinicaltrials.gov/ct2/show/NCT02590029.
PMID- 28702871
TI - Expression of podoplanin in stromal fibroblasts plays a pivotal role in the
prognosis of patients with pancreatic cancer.
AB - PURPOSE: To investigate the role of podoplanin (PDPN) expression in invasive
ductal carcinoma of the pancreas (IDCP) in humans. METHODS: Tumor samples were
obtained from 95 patients with IDCP. Immunohistochemical staining was done to
evaluate the expression of PDPN in cancer tissues. RESULTS: PDPN was detected
predominantly in stromal fibroblasts, stained with alpha-smooth muscle actin. The
cutoff value of PDPN-positive areas was calculated according to a histogram.
There was no significant difference in clinicopathologic factors between patients
with high vs. those with low PDPN expression. The high PDPN group showed
significantly poorer disease-free and disease-specific survival rates than the
low PDPN group. Among patients from the high PDPN group, those with lymph node
metastases and those with a tumor larger than 20 cm in diameter had significantly
poorer prognoses than similar patients from the low PDPN group. Multivariate Cox
proportional hazards analysis indicated that a high expression of PDPN was an
independent risk factor for disease-specific survival. CONCLUSIONS: PDPN
expression in cancer-related fibrotic tissues is associated with a poor
prognosis, especially in patients with large tumors or lymph node metastases.
PMID- 28702872
TI - Dietary Supplementation of Selenium-Enriched Probiotics Enhances Meat Quality of
Broiler Chickens (Gallus gallus domesticus) Raised Under High Ambient
Temperature.
AB - We investigated the effects of selenium-enriched probiotics (SP) on broiler meat
quality under high ambient temperature and explore their underlying mechanisms. A
total of 200 1-day-old male broiler chicks (Ross 308) were randomly allotted to
four treatment groups, each with five replicates, in groups of ten birds. These
birds were fed a corn-soybean basal diet (C), a basal diet plus probiotics
supplementation (P), a basal diet plus Se supplementation in the form of sodium
selenite (SS, 0.30 mg Se/kg), and a basal diet with the addition of selenium
enriched probiotics (SP, 0.30 mg Se/kg). The experiment lasted for 42 days. The
birds were sacrificed by cervical dislocation, and the breast muscles were
removed for further process. Our results showed that SP diet significantly
increased (p < 0.05) the physical (pH, colors, water holding capacity, drip loss,
shear force) and sensory characteristics of breast meat. All P, SS, and SP
supplementation enhanced the antioxidant system by increasing (p < 0.05) the Se
concentrations, glutathione (GSH) levels, activities of glutathione peroxidase
(GSH-Px), and superoxide dismutase (SOD) whereas decreasing (p < 0.05)
malondialdehyde (MDA) levels, with SP being higher than P and SS. Moreover, SP
diet significantly upregulated (p < 0.05) the mRNA levels of glutathione
peroxidase genes (GPx1, GPx4) while it downregulated heat stress biomarkers such
as heat shock protein (HSP) 70 as compared to C, P, and SS diets. In conclusion,
our findings suggest that SP may function as beneficial nutritive supplement that
is capable of improving meat quality during the summer season.
PMID- 28702873
TI - Trace Elements Characteristic Based on ICP-AES and the Correlation of Flavonoids
from Sparganii rhizoma.
AB - The aim of the present work was to investigate the trace elements and the
correlation with flavonoids from Sparganii rhizoma. The ICP-AES and ultraviolet
visible spectroscopy were employed to analyze trace elements and flavonoids. The
concentrations of trace elements and flavonoids were calculated using standard
curve. The content of flavonoids was expressed as rutin equivalents. The cluster
analysis was applied to evaluate geographical features of S. rhizoma from
different geographical regions. The correlation analysis was used to obtain the
relationship between the trace elements and flavonoids. The results indicated
that the 15 trace elements were measured and the K, Ca, Mg, Na, Mn, Al, Cu, and
Zn are rich in Sparganii rhizome. The different producing regions samples were
classified into four groups. There was a weak relationship between trace elements
and flavonoids.
PMID- 28702874
TI - Towards a Transparent, Credible, Evidence-Based Decision-Making Process of New
Drug Listing on the Hong Kong Hospital Authority Drug Formulary: Challenges and
Suggestions.
AB - The aim of this article is to describe the process, evaluation criteria, and
possible outcomes of decision-making for new drugs listed in the Hong Kong
Hospital Authority Drug Formulary in comparison to the health technology
assessment (HTA) policy overseas. Details of decision-making processes including
the new drug listing submission, Drug Advisory Committee (DAC) meeting, and
procedures prior to and following the meeting, were extracted from the official
Hong Kong Hospital Authority drug formulary management website and manual.
Publicly-available information related to the new drug decision-making process
for five HTA agencies [the National Institute of Health and Care Excellence
(NICE), the Scottish Medicines Consortium (SMC), the Australia Pharmaceutical
Benefits Advisory Committee (PBAC), the Canadian Agency for Drugs and
Technologies in Health (CADTH), and the New Zealand Pharmaceutical Management
Agency (PHARMAC)] were reviewed and retrieved from official documents from public
domains. The DAC is in charge of systemically and critically appraising new drugs
before they are listed on the formulary, reviewing submitted applications, and
making the decision to list the drug based on scientific evidence to which
safety, efficacy, and cost-effectiveness are the primary considerations. When
compared with other HTA agencies, transparency of the decision-making process of
the DAC, the relevance of clinical and health economic evidence, and the lack of
health economic and methodological input of submissions are the major challenges
to the new-drug listing policy in Hong Kong. Despite these challenges, this
review provides suggestions for the establishment of a more transparent,
credible, and evidence-based decision-making process in the Hong Kong Hospital
Authority Drug Formulary. Proposals for improvement in the listing of new drugs
in the formulary should be a priority of healthcare reforms.
PMID- 28702875
TI - Private Health Insurance Incentives in Australia: In Search of Cost-Effective
Adjustments.
AB - BACKGROUND: The appropriate structure, scope and cost of government incentives in
the private health insurance (PHI) market is a matter of ongoing debate.
OBJECTIVE: In order to inform policy decisions we designed a two-stage study to
(1) model the uptake of PHI covering hospital treatment in Australia, and (2)
identify the costs of various policy scenarios to the government. METHODS: Using
a microsimulation with a cost-benefit component, we modelled the insurance
decisions made by individuals who collectively represented the Australian
insurance population in the financial year 2014-15. RESULTS: We found that the
mean willingness to pay (WTP) for PHI ranged from A$446 to A$1237 per year
depending on age and income. Our policy scenarios showed a considerable range of
impacts on the government budget (from A$4 billion savings to A$6 billion
expense) and PHI uptake (from 3.4 million fewer to 2.5 million more individuals
insured), with cost-effectiveness ranging from -A$305 to A$22,624 per additional
person insured, relative to the status quo. CONCLUSIONS: Based on the scenario
results we recommend policy adjustments that either increase the PHI uptake at a
small per-person cost to the public budget or substantially reduce government
subsidisation of PHI at a relatively small loss in terms of persons insured.
PMID- 28702876
TI - Cardiovascular Histopathology of a 11-Year Old with Mucopolysaccharidosis VII
Demonstrates Fibrosis, Macrophage Infiltration, and Arterial Luminal Stenosis.
AB - Mucopolysaccharidosis type VII (MPS VII) is caused by beta-glucuronidase
deficiency, resulting in lysosomal accumulation of glycosaminoglycans (GAGs) and
multisystemic disease. We present cardiovascular gross and histopathology
findings from a 11-year-old MPS VII male, who expired after developing
ventricular fibrillation following anesthesia induction. Gross anatomic
observations were made at autopsy; postmortem formalin-fixed paraffin-embedded
samples of the carotid artery, aorta, myocardium, and valves were sectioned and
stained with hematoxylin-eosin, Verhoeff-Van Gieson, CD68, and trichrome stains.
Gross heart findings include an enlarged, dilated heart, mitral valve prolapse
with thick, shortened chordae tendinae, and thickened aortic valve cusps. The
aorta contained raised intimal plaques mimicking conventional atherosclerosis.
Cardiac myocytes included hypertrophic nuclei, subendocardial fibrosis, and
increased interfascicular collagen. Coronary lumens were 40-70% stenosed by
fibrointimal hyperplasia containing storage material-laden cells, CD68+
macrophages, and fragmented elastin laminae. Similar findings were visualized in
aortic intimal plaques. We confirm that arterial plaques, elastin fragmentation,
and activated CD68+ macrophage infiltration occur in human MPS VII, consistent
with previously observed findings in murine and canine MPS VII. We also confirm
ultrasonographically observed carotid intimal-medial thickening is an in vivo
correlate of histopathologic vascular fibrointimal hyperplasia. MPS VII patients
should be regularly monitored for cardiac disease, with methods such as Holter
monitors and stress testing; MPS VII-directed treatments should effectively
address cardiovascular disease.
PMID- 28702877
TI - Absorption, Distribution, Metabolism, and Excretion of [14C]-Volixibat in Healthy
Men: Phase 1 Open-Label Study.
AB - BACKGROUND AND OBJECTIVES: Volixibat is a potent inhibitor of the apical sodium
dependent bile acid transporter in development for the treatment of nonalcoholic
steatohepatitis. This phase 1, open-label study investigated the absorption,
distribution, metabolism, and excretion of [14C]-volixibat in heathy men.
METHODS: Eligible men (n = 8) aged 18-50 years (body mass index 18.0-30.0 kg/m2;
weight >50 kg) received a single oral dose of [14C]-volixibat 50 mg containing
~5.95 uCi radioactivity. The primary objectives were to assess the
pharmacokinetics of [14C]-volixibat and to determine the total radioactivity in
whole blood, plasma, urine, and feces at pre-selected time points over 6 days.
The secondary objectives were to characterize metabolites and to assess the
safety and tolerability. RESULTS: Low concentrations of volixibat (range 0-0.179
ng/mL) were detected in plasma up to 8 h following administration; the
pharmacokinetic parameters could not be calculated. No radioactivity was observed
in plasma or whole blood. The percentage (mean +/- standard deviation) of total
radioactivity in urine was 0.01 +/- 0.007%. The vast majority (92.3 +/- 5.25%) of
volixibat was recovered in feces (69.2 +/- 33.1% within 24 h). Unchanged
volixibat was the only radioactive component detected in feces. Adverse events
were mild in severity and mostly gastrointestinal. Changes in laboratory values
were not clinically meaningful. CONCLUSIONS: Following oral administration, [14C]
volixibat was excreted unchanged from the parent compound almost exclusively via
fecal excretion, indicating that the drug is minimally absorbed. Consistent with
other studies, adverse events were primarily gastrointestinal in nature.
ClinicalTrials.gov identifier NCT02571192.
PMID- 28702878
TI - Recent Trends in Clot Retrieval Devices: A Review.
AB - Stroke is the second leading cause of death worldwide and in Europe. Even with
gold standard medical management of acute ischemic stroke, which is intravenous
(IV) thrombolysis by administration of recombinant tissue plasminogen activator
(rt-PA), the mortality rate remains the same. Intra-arterial (IA) thrombolysis
therapy also did not achieve significant results and was not approved by the US
Food and Drug Administration (FDA) because of limited sample size. This
encouraged scientists and engineers to develop endovascular clot retrieval
devices for the mechanical recanalization of the occluded arteries in stroke
patients. Although the initial designs of clot retrieval devices failed, efforts
to improve these devices continue. Recently clot retrieval devices were approved
by the FDA as first-line treatment along with IV rt-PA. This article gives an in
depth review of different clot retrieval devices which includes MERCI (the
first), the Penumbra Aspiration System, EmboTrap(r)II, stent retrievers, and the
way forward with the new FDA clearance of the devices as first-line treatment for
acute ischemic stroke along with IV rt-PA. The review also includes a comparison
of clot retrieval devices to gold standard treatment.
PMID- 28702879
TI - Assessment of genotoxicity amongst smokers, alcoholics, and tobacco chewers of
North India using micronucleus assay and urinary 8-hydroxyl-2'-deoxyguanosine, as
biomarkers.
AB - The main objective of the present study was to screen the genotoxicity caused by
individual and combined habits of smoking, tobacco chewing, and alcohol
consumption in human population of North India. Study recruited 67 male subjects
aged 25 to 65 years. Buccal mucosal cells were subjected to micronucleus (MN)
assay, and 8-hydroxyl-2-deoxyguanosine (8-OHdG) was estimated in their urine
samples. Number and shape of the MN cells varied in the buccal epithelium of
different groups. Maximum number of MN (0.47%) were found in tobacco chewers
followed by smokers (0.45%) and alcoholics (0.44%) (P < 0.05). These results
reciprocated the concentration of urinary 8-OHdG. Maximum value for 8-OHdG was
also recorded in tobacco chewers (21.07 +/- 5.51 mg/mg creatinine) followed by
smokers (20.25 +/- 3.96 mg/mg creatinine) and alcoholics (19.06 +/- 3.41 mg/mg
creatinine) (P < 0.05). Combined effects of these agents were found to be
statistically different from individual effects. Carcinogenic compounds present
in cigarette smoke, nitrosamines found in solid tobacco, and acetaldehyde, a
metabolic product of alcohol, induce oxidative stress that manifests into
genotoxicity. In conclusion, demographical differences occur in the genotoxicity
caused by these three habits. MN assay and urinary 8-OHdG are simple,
noninvasive, and reliable biomarkers of genotoxicity.
PMID- 28702880
TI - Atrial fibrillation in immigrant groups: a cohort study of all adults 45 years of
age and older in Sweden.
AB - To study the association between country of birth and incident atrial
fibrillation (AF) in several immigrant groups in Sweden. The study population
included all adults (n = 3,226,752) aged 45 years and older in Sweden. AF was
defined as having at least one registered diagnosis of AF in the National Patient
Register. The incidence of AF in different immigrant groups, using Swedish-born
as referents, was assessed by Cox regression, expressed in hazard ratios (HRs)
and 95% confidence intervals (CI). All models were stratified by sex and adjusted
for age, geographical residence in Sweden, educational level, marital status, and
neighbourhood socioeconomic status. Compared to their Swedish-born counterparts,
higher incidence of AF [HR (95% CI)] was observed among men from Bosnia 1.74
(1.56-1.94) and Latvia 1.29 (1.09-1.54), and among women from Iraq 1.96 (1.67
2.31), Bosnia 1.88 (1.61-1.94), Finland 1.14 (1.11-1.17), Estonia 1.14 (1.05
1.24) and Germany 1.08 (1.03-1.14). Lower incidence of AF was noted among men
(HRs <= 0.60) from Iceland, Southern Europe (especially Greece, Italy and Spain),
Latin America (especially Chile), Africa, Asia (including Iraq, Turkey, Lebanon
and Iran), and among women from Nordic countries (except Finland), Southern
Europe, Western Europe (except Germany), Africa, North America, Latin America,
Iran, Lebanon and other Asian countries (except Turkey and Iraq). In conclusion,
we observed substantial differences in incidence of AF between immigrant groups
and the Swedish-born population. A greater awareness of the increased risk of AF
development in some immigrant groups may enable for a timely diagnosis, treatment
and prevention of its debilitating complications, such as stroke.
PMID- 28702881
TI - [Angiotensin II as an alternative nonadrenergic vasopressor : Results of a
randomized, double-blind, placebo-controlled efficacy study].
PMID- 28702882
TI - Near-Misses and Stop Buttons in Slot Machine Play: An Investigation of How They
Affect Players, and May Foster Erroneous Cognitions.
AB - In modern casinos, multiline slot machines are becoming increasingly popular
compared to traditional, three-reel slot machines. A paucity of research has
examined how the unique presentation of near-misses and the use of a stop button
in multiline slot machines impact erroneous cognitions related to the perception
of skill and agency during play. Our goal therefore was to determine the
prevalence of erroneous cognitions pertaining to near-miss outcomes and the usage
of a stop button and then to see whether the stop button affected players'
experiences of winning, losing and near-miss outcomes. We recruited 132 gamblers
from a casino in Ontario. They played two versions of a slot machine simulator:
one with a stop button and one without a stop button. We measured player's
arousal [skin conductance responses (SCRs), pressure on the spin-button), and
behavioural responses (post-reinforcement pauses (PRPs)] to wins, losses and near
misses during play. We predicted more robust physiological SCRs and longer PRPs
to wins in the stop button game. We also predicted that near-misses encountered
in the stop button game would trigger greater levels of arousal and frustration
in players, as indexed by larger SCRs, and greater force applied to the spin
button to initiate the next spin. Erroneous cognitions pertaining to the stop
button and near-misses respectively were assessed following play. Results showed
that a small but meaningful percentage of players held erroneous cognitions about
the stop button (13.6%) and near-misses (16%). Players depressed the spin button
harder, and had larger SCRs for all outcomes when using the stop button. Players
also paused longer for near-misses in the game involving the stop button. Our
findings converge to suggest that the stop button encourages an erroneous
perception of skill in some players, and consequentially impacts how such players
perceive their outcomes in multiline slot machines.
PMID- 28702883
TI - Risk factors for recurrent emergency department visits for hyperglycemia in
patients with diabetes mellitus.
AB - BACKGROUND: Patients with poorly controlled diabetes mellitus may present
repeatedly to the emergency department (ED) for management and treatment of
hyperglycemic episodes, including diabetic ketoacidosis and hyperosmolar
hyperglycemic state. The objective of this study was to identify risk factors
that predict unplanned recurrent ED visits for hyperglycemia in patients with
diabetes within 30 days of initial presentation. METHODS: We conducted a 1-year
health records review of patients >=18 years presenting to one of four tertiary
care EDs with a discharge diagnosis of hyperglycemia, diabetic ketoacidosis, or
hyperosmolar hyperglycemic state. Trained research personnel collected data on
patient characteristics and determined if patients had an unplanned recurrent ED
visit for hyperglycemia within 30 days of their initial presentation.
Multivariate logistic regression models using generalized estimating equations to
account for patients with multiple visits determined predictor variables
independently associated with recurrent ED visits for hyperglycemia within 30
days. RESULTS: There were 833 ED visits for hyperglycemia in the 1-year period.
54.6% were male and mean (SD) age was 48.8 (19.5). Of all visitors, 156 (18.7%)
had a recurrent ED visit for hyperglycemia within 30 days. Factors independently
associated with recurrent hyperglycemia visits included a previous hyperglycemia
visit in the past month (odds ratio [OR] 3.5, 95% confidence interval [CI] 2.1
5.8), age <25 years (OR 2.6, 95% CI 1.5-4.7), glucose >20 mmol/L (OR 2.2, 95% CI
1.3-3.7), having a family physician (OR 2.2, 95% CI 1.0-4.6), and being on
insulin (OR 1.9, 95% CI 1.1-3.1). Having a systolic blood pressure between 90-150
mmHg (OR 0.53, 95% CI 0.30-0.93) and heart rate >110 bpm (OR 0.41, 95% CI 0.23
0.72) were protective factors independently associated with not having a
recurrent hyperglycemia visit. CONCLUSIONS: This unique ED-based study reports
five risk factors and two protective factors associated with recurrent ED visits
for hyperglycemia within 30 days in patients with diabetes. These risk factors
should be considered by clinicians when making management, prognostic, and
disposition decisions for diabetic patients who present with hyperglycemia.
PMID- 28702884
TI - Decellularization of Large Tendon Specimens: Combination of Manually Performed
Freeze-Thaw Cycles and Detergent Treatment.
AB - Reliable decellularization techniques applicable to tendon tissue play a critical
role in the field of current tissue engineering. Particularly, an application as
three-dimensional culture model for in vitro research and translational
approaches to establish graft-based tendon repair as a routine clinical tool
represent two main application fields for decellularized tendon scaffolds.
Considering methodological issues of tendon decellularization, one of the major
challenges lies in the preservation of the tendon-specific extracellular matrix
(ECM) architecture to reflect natural tissue characteristic as best as possible.
Concurrently, further requirements for high-quality decellularized biological
tendon scaffolds include not only the reduction of resident cells, but also an
ensured cytocompatibility.To date, a large number and a wide variety of
decellularization protocols for natural tendon tissue have already been
investigated and usually, physical as well as chemical and/or enzyme-based
treatments are used for the purpose of decellularization. However, to the best of
our knowledge, there is a lack of evidence-based protocols for the processing of
full-thickness large tendon samples, such as the equine flexor tendons.Therefore,
the here presented protocol describes a reliable procedure to decellularize
equine superficial digital flexor tendons by using a combined treatment of
physical decellularization in the form of repetitive freeze-thaw cycles, and of
chemical decellularization with the non-ionic detergent Triton X-100. The
decellularization effectiveness evaluated by reduction of cell and DNA content,
the influence of decellularization on the morphology of the tendon extracellular
matrix (ECM) as well as the cytocompatibility of the decellularized tendon
scaffolds obtained have been investigated previously. Based on this previous
study, the here present protocol is an effective procedure, particularly
applicable for large tendon specimens.
PMID- 28702885
TI - Use of a Super-hydrophobic Microbioreactor to Generate and Boost Pancreatic Mini
organoids.
AB - Cell remarkable ability to self-organize and rearrange in functional organoids
has been greatly boosted by the recent advances in 3-D culture technologies and
materials. This approach can be presently applied to model human organ
development and function "in a dish" and to predict drug response in a patient
specific fashion.Here we describe a protocol that allows for the derivation of
functional pancreatic mini-organoids from skin biopsies. Cells are suspended in a
drop of medium and encapsulated with hydrophobic polytetrafluoroethylene (PTFE)
powder particles, to form microbioreactors defined as "Liquid Marbles," that
stimulate cell coalescence and 3-D aggregation. The PTFE shell ensures an optimal
gas exchange between the interior liquid and the surrounding environment. It also
makes it possible to scale down experiments and work in smaller volumes and is
therefore amenable for higher throughput applications.
PMID- 28702886
TI - Comparison of transvaginal sonography and computed tomography-colonography with
contrast media and urographic phase for diagnosing deep infiltrating
endometriosis of the posterior compartment of the pelvis: a pilot study.
AB - PURPOSE: To compare the diagnostic accuracy of transvaginal sonography (TVS) and
computed tomography-colonography with contrast media and urographic phase (CTCU)
in the preoperative detection of deep infiltrating endometriosis (DIE). MATERIALS
AND METHODS: Forty-seven patients with clinical suspicion of DIE underwent
preoperative TVS and CTCU. Imaging data were compared with histopathologic
analysis. Sensitivity, specificity, positive and negative predictive values and
test accuracies of the two modalities were calculated. RESULTS: For diagnosing
intestinal DIE, TVS and CTCU had a sensitivity of 98 and 71%, specificity of 33
and 50%, positive predictive value of 91 and 91%, negative predictive value of 67
and 20%, accuracy of 89 and 68%, respectively. For diagnosing ureteral DIE, TVS
and CTCU had a sensitivity of 10 and 60%, specificity of 94.8 and 70.2% on the
right; sensitivity of 28.5 and 57.1%, specificity of 96.3 and 76.9% on the left,
respectively. CONCLUSION: TVS should be regarded as an accurate, radiation-free
first-line diagnostic modality for patients with suspicion of posterior
endometriosis. CTCU should be regarded as a complementary imaging modality,
particularly for sigmoid or ureteral endometriosis.
PMID- 28702887
TI - Ambulatory blood pressure monitoring-derived short-term blood pressure
variability in primary hyperparathyroidism.
AB - INTRODUCTION: Primary hyperparathyroidism is associated with a cluster of
cardiovascular manifestations, including hypertension, leading to increased
cardiovascular risk. PURPOSE: The aim of our study was to investigate the
ambulatory blood pressure monitoring-derived short-term blood pressure
variability in patients with primary hyperparathyroidism, in comparison with
patients with essential hypertension and normotensive controls. METHODS: Twenty
five patients with primary hyperparathyroidism (7 normotensive,18 hypertensive)
underwent ambulatory blood pressure monitoring at diagnosis, and fifteen out of
them were re-evaluated after parathyroidectomy. Short-term-blood pressure
variability was derived from ambulatory blood pressure monitoring and calculated
as the following: 1) Standard Deviation of 24-h, day-time and night-time-BP; 2)
the average of day-time and night-time-Standard Deviation, weighted for the
duration of the day and night periods (24-h "weighted" Standard Deviation of BP);
3) average real variability, i.e., the average of the absolute differences
between all consecutive BP measurements. RESULTS: Baseline data of normotensive
and essential hypertension patients were matched for age, sex, BMI and 24-h
ambulatory blood pressure monitoring values with normotensive and hypertensive
primary hyperparathyroidism patients, respectively. Normotensive-primary
hyperparathyroidism patients showed a 24-h weighted Standard Deviation (P < 0.01)
and average real variability (P < 0.05) of systolic blood pressure higher than
that of 12 normotensive controls. 24-h average real variability of systolic BP,
as well as serum calcium and parathyroid hormone levels, were reduced in operated
patients (P < 0.001). A positive correlation of serum calcium and parathyroid
hormone with 24-h-average real variability of systolic BP was observed in the
entire primary hyperparathyroidism patients group (P = 0.04, P = 0.02;
respectively). CONCLUSION: Systolic blood pressure variability is increased in
normotensive patients with primary hyperparathyroidism and is reduced by
parathyroidectomy, and may potentially represent an additional cardiovascular
risk factor in this disease.
PMID- 28702888
TI - Cushing's syndrome: a model for sarcopenic obesity.
AB - PURPOSE: Obesity and its metabolic impairments are discussed as major risk
factors for sarcopenia leading to sarcopenic obesity. Cushing's syndrome is known
to be associated with obesity and muscle atrophy. We compared Cushing's syndrome
with matched obese controls regarding body composition, physical performance, and
biochemical markers to test the hypothesis that Cushing's syndrome could be a
model for sarcopenic obesity. METHODS: By propensity score matching, 47 controls
were selected by body mass index and gender as obese controls. Fat mass and
muscle mass were measured by bioelectrical impedance analysis. Muscle function
was assessed by chair rising test and hand grip strength. Biochemical markers of
glucose and lipid metabolism and inflammation (hsCRP) were measured in peripheral
blood. RESULTS: Muscle mass did not differ between Cushing's syndrome and obese
controls. However, Cushing's syndrome patients showed significantly greater chair
rising time (9.5 s vs. 7.3 s, p = 0.008) and significantly lower hand grip
strength (32.1 kg vs. 36.8 kg, p = 0.003). Cushing's syndrome patients with
impaired fasting glucose have shown the highest limitations in hand grip strength
and chair rising time. CONCLUSIONS: Similar to published data in ageing medicine,
Cushing's syndrome patients show loss of muscle function that cannot be explained
by loss of muscle mass. Impaired muscle quality due to fat infiltration may be
the reason. This is supported by the observation that Cushing's syndrome patients
with impaired glucose metabolism show strongest deterioration of muscle function.
Research in sarcopenic obesity in elderly is hampered by confounding
comorbidities and polypharmacy. As Cushing's syndrome patients are frequently
free of comorbidities and as Cushing's syndrome is potentially curable we suggest
Cushing's syndrome as a clinical model for further research in sarcopenic
obesity.
PMID- 28702889
TI - Treatment of refractory and severe hypothyroidism with sublingual levothyroxine
in liquid formulation.
PMID- 28702890
TI - Adiposity during early adulthood, changes in adiposity during adulthood, attained
adiposity, and mammographic density among premenopausal women.
AB - PURPOSE: We investigated the associations of adolescent adiposity, changes in
adiposity during adulthood, and attained adiposity with volumetric mammographic
density measures. METHODS: We recruited 383 premenopausal women who had a routine
screening mammogram at the Breast Health Center, Washington University in St.
Louis, MO from December 2015 to October 2016. Trained research personnel assessed
current adiposity measures. Weight at ages 18 and 30 were self-reported. We
evaluated mammographic density measures: volumetric percent density (VPD), dense
volume (DV), and non-dense volume (NDV) using Volpara. Multivariable linear
regression models were used to evaluate the associations of adiposity measures
with volumetric mammographic density measures. RESULTS: All attained adiposity
measures, BMI at age 18, age 30, and weight change were significantly inversely
associated with VPD, and positively associated with DV and NDV. One unit increase
in body fat % was associated with a 4.9% decrease in VPD and a 6.5% increase in
NDV (p-values <0.001). For each kilogram increase in weight change from age 18 to
attained, VPD decreased by 16.3%, 47.1%, and 58.8% for women who gained 5.1-15,
15.1-25 and >25 kg, respectively, compared to women who gained less than 5 kg
during this time period (p-values <0.001). Irrespective of BMI at age 18, VPD
significantly decreased and NDV increased among women who were currently obese.
CONCLUSIONS: There is a need for mechanistic studies focusing on early adulthood
to provide a better understanding of how adiposity in early life relates to
mammographic density, and possibly breast cancer development in premenopausal
women.
PMID- 28702891
TI - Predictors associated with MRI surveillance screening in women with a personal
history of unilateral breast cancer but without a genetic predisposition for
future contralateral breast cancer.
AB - PURPOSE: For women with a personal history of breast cancer (PHBC), no validated
mechanisms exist to calculate future contralateral breast cancer (CBC) risk. The
Manchester risk stratification guidelines were developed to evaluate CBC risk in
women with a PHBC, primarily for surgical decision making. This tool may be
informative for the use of MRI screening, as CBC risk is an assumed consideration
for high-risk surveillance. METHODS: Three hundred twenty-two women with a PHBC
were treated with unilateral surgery within our multidisciplinary breast clinic.
We calculated lifetime CBC risk using the Manchester tool, which incorporates age
at diagnosis, family history, genetic mutation status, estrogen receptor
positivity, and endocrine therapy use. Univariate and multivariate logistic
regression analyses (UVA/MVA) were performed, evaluating whether CBC risk
predicted MRI surveillance. RESULTS: For women with invasive disease undergoing
MRI surveillance, 66% had low, 23% above-average, and 11% moderate/high risk for
CBC. On MVA, previous mammography-occult breast cancer [odds ratio (OR) 18.95, p
< 0.0001], endocrine therapy use (OR 3.89, p = 0.009), dense breast tissue (OR
3.69, p = 0.0007), mastectomy versus lumpectomy (OR 3.12, p = 0.0041), and CBC
risk (OR 3.17 for every 10% increase, p = 0.0002) were associated with MRI
surveillance. No pathologic factors increasing ipsilateral breast cancer
recurrence were significant on MVA. CONCLUSIONS: Although CBC risk predicted MRI
surveillance, 89% with invasive disease undergoing MRI had <20% calculated CBC
risk. Concerns related to future breast cancer detectability (dense breasts
and/or previous mammography-occult disease) predominate decision making.
Pathologic factors important for determining ipsilateral recurrence risk, aside
from age, were not associated with MRI surveillance.
PMID- 28702892
TI - A small-molecule inhibitor of SMAD3 attenuates resistance to anti-HER2 drugs in
HER2-positive breast cancer cells.
AB - PURPOSE: Resistance against anti-HER2 drugs in HER2-positive breast cancer is a
major obstacle to the improving prognosis. Transforming growth factor beta
(TGFbeta) is a cytokine involved in the acquisition of more malignant phenotypes
through epithelial-mesenchymal transition (EMT) and cancer stem cell (CSC)
properties. The aim of this study was to investigate the effects of TGFbeta and
its downstream SMAD pathway on resistance to anti-HER2 drugs. METHODS: HER2
positive breast cancer cell lines were stimulated with TGFbeta for 14 days. Then,
the sensitivity to trastuzumab and lapatinib and the expression levels of various
EMT and CSC markers were examined. The correlation of nuclear SMAD3 expression in
untreated breast tumor tissues with trastuzumab efficacy in neoadjuvant settings
was examined. The effect of a small-molecule inhibitor of SMAD3 (SIS3) on
resistance to anti-HER2 drugs was explored. RESULTS: We found that continuous
activation of the TGFbeta-SMAD3 pathway induced resistance to anti-HER2 drugs and
CSC traits in HER2-positive breast cancer cells. The induction of drug resistance
by TGFbeta required strong activation of SMAD3. In fact, activated SMAD3
regulated multiple genes that harbor SMAD-binding elements and are involved in
trastuzumab resistance. Nuclear SMAD3 expression in tumor tissue was inversely
correlated with sensitivity to neoadjuvant treatment with trastuzumab. SIS3 not
only prevented the acquisition of resistance to anti-HER2 drugs but also restored
trastuzumab sensitivity in trastuzumab-resistant cells. CONCLUSIONS: This study
indicates that the TGFbeta-SMAD3 pathway plays an important role in the induction
and maintenance of resistance to anti-HER2 drugs. Thus, SMAD3 is a potential
therapeutic target that can inhibit resistance and restore sensitivity to anti
HER2 drugs.
PMID- 28702893
TI - Medical costs of treating breast cancer among younger Medicaid beneficiaries by
stage at diagnosis.
AB - BACKGROUND: Younger women (aged 18-44 years) diagnosed with breast cancer often
face more aggressive tumors, higher treatment intensity, and lower survival rates
than older women. In this study, we estimated incident breast cancer costs by
stage at diagnosis and by race for younger women enrolled in Medicaid. METHODS:
We analyzed cancer registry data linked to Medicaid claims in North Carolina from
2003 to 2008. We used Surveillance, Epidemiology, and End Results (SEER) Summary
2000 definitions for cancer stage. We split breast cancer patients into two
cohorts: a younger and older group aged 18-44 and 45-64 years, respectively. We
conducted a many-to-one match between patients with and without breast cancer
using age, county, race, and Charlson Comorbidity Index. We calculated mean
excess total cost of care between breast cancer and non-breast cancer patients.
RESULTS: At diagnosis, younger women had a higher proportion of regional cancers
than older women (49 vs. 42%) and lower proportions of localized cancers (44 vs.
50%) and distant cancers (7 vs. 9%). The excess costs of breast cancer (all
stages) for younger and older women at 6 months after diagnosis were $37,114 [95%
confidence interval (CI) = $35,769-38,459] and $28,026 (95% CI = $27,223-28,829),
respectively. In the 6 months after diagnosis, the estimated excess cost was
significantly higher to treat localized and regional cancer among younger women
than among older women. There were no statistically significant differences in
excess costs of breast cancer by race, but differences in treatment modality were
present among younger Medicaid beneficiaries. CONCLUSIONS: Younger breast cancer
patients not only had a higher prevalence of late-stage cancer than older women,
but also had higher within-stage excess costs.
PMID- 28702894
TI - 21-Gene recurrence score and locoregional recurrence in lymph node-negative,
estrogen receptor-positive breast cancer.
AB - BACKGROUND/PURPOSE: The 21-gene recurrence score (RS) assay evaluates the
likelihood of distant recurrence and benefit of chemotherapy in lymph node
negative, estrogen receptor (ER)-positive, HER2-negative breast cancer patients.
The RS categories are associated with the risk of locoregional recurrence (LRR)
in some, but not all studies. METHODS: We reviewed the institutional database to
identify consecutive female patients with node-negative, ER+/HER2- breast
carcinoma tested for the 21-gene RS assay and treated at our center from 2008 to
2013. We collected data on clinicopathologic features, treatment, and outcome.
Statistical analysis was performed using SAS version 9.4 or R version 3.3.2.
RESULTS: Of 2326 patients, 60% (1394) were in the low RS group, 33.4% (777) in
the intermediate RS group, and 6.6% (155) in the high RS group. Median follow-up
was 53 months. A total of 44 LRRs were observed, with a cumulative incidence of
0.17% at 12 months and 1.6% at 48 months. The cumulative incidence of LRR at 48
months was 0.84%, 2.72% and 2.80% for low, intermediate, and high RS groups,
respectively (p < 0.01). Univariate analysis showed that the risk of LRR was
associated with the RS categories (p < 0.01), T stage (p < 0.01) and
lymphovascular invasion (LVI) (p = 0.009). There was no difference in LRR rates
by initial local treatment (total mastectomy vs. breast-conserving surgery plus
radiation therapy). The RS remained significantly associated with LRR after
adjusting for LVI and T stage. Compared to patients with low RS, the risk of LRR
was increased more than 4-fold (hazard ratio: 4.61, 95% CI 1.90-11.19, p < 0.01),
and 3-fold (hazard ratio: 2.81, 95% CI 1.41-5.56, p < 0.01) for high and
intermediate risk categories, respectively. CONCLUSIONS: Our study confirms that
RS is significantly associated with the risk of LRR in node-negative, ER+/HER2-
breast cancer patients. Our findings suggest that in addition to its value for
prognostic stage grouping and decision-making regarding adjuvant systemic
therapy, the role of the RS in identifying patients not requiring radiotherapy
should be studied.
PMID- 28702895
TI - FANCM mutation c.5791C>T is a risk factor for triple-negative breast cancer in
the Finnish population.
AB - PURPOSE: The FANCM c.5101C>T nonsense mutation was previously found to associate
with breast cancer in the Finnish population, especially among triple-negative
cases. Here, we studied the prevalence of three other FANCM variants: c.5791C>T,
which has been reported to predispose to familial breast cancer, and the
c.4025_4026delCT and c.5293dupA variants recently identified in Finnish cancer
patients. METHODS: We genotyped the FANCM c.5791C>T mutation in 4806 invasive
breast cancer patients, including BRCA1/2 mutation negative familial cases and
unselected cases, and in 2734 healthy population controls from four different
geographical areas of Finland. The association of the mutation with breast cancer
risk among patient subgroups was statistically evaluated. We further analyzed the
combined risk associated with c.5101C>T and c.5791C>T mutations. We also
genotyped 526 unselected ovarian cancer patients for the c.5791C>T mutation and
862 familial breast cancer patients for the c.4025_4026delCT and c.5293dupA
variants. RESULTS: The frequency of the FANCM c.5791C>T mutation was higher among
breast cancer cases than in controls (OR 1.94, 95% CI 0.87-4.32, P = 0.11), with
a statistically significant association with triple-negative breast cancer (OR
5.14, 95% CI 1.65-16.0, P = 0.005). The combined analysis for c.5101C>T and
c.5791C>T carriers confirmed a strong association with breast cancer (OR 1.86,
95% CI 1.32-2.49, P = 0.0002), especially among the triple-negative patients (OR
3.08, 95% CI 1.77-5.35, P = 0.00007). For the other variants, only one additional
c.4025_4026delCT carrier and no c.5293dupA carriers were observed. CONCLUSIONS:
These results support the role of FANCM as a breast cancer susceptibility gene,
particularly for triple-negative breast cancer.
PMID- 28702896
TI - Breast cancer risk prediction: an update to the Rosner-Colditz breast cancer
incidence model.
AB - PURPOSE: To update and expand the Rosner-Colditz breast cancer incidence model by
evaluating the contributions of more recently identified risk factors as well as
predicted percent mammographic density (MD) to breast cancer risk. METHODS: Using
data from the Nurses' Health Study (NHS) and NHSII, we added adolescent
somatotype (9 unit scale), vegetable intake (servings/day), breastfeeding
(months), physical activity (MET-h/week), and predicted percent MD to the Rosner
Colditz model to determine whether these variables improved model discrimination.
We evaluated all invasive as well as ER+/PR+, ER+/PR-, and ER-/PR- breast cancer.
RESULTS: In the NHS/NHSII, we accrued over 5200 cases of invasive breast cancer
over more than 20 years of follow-up with complete data on the risk factors.
Adolescent somatotype and predicted percent MD significantly improved the
original Rosner-Colditz model for all invasive breast cancer (change in age
adjusted AUC = 0.020, p < 0.001). The relative risk (RR) of invasive breast
cancer for a 4-unit increase in adolescent somatotype was 0.62 (95% CI 0.56,
0.70), whereas the RR for a 20-unit increase in predicted percent MD was 1.32
(95% CI 1.28, 1.36). Adolescent somatotype and predicted percent MD also
significantly improved the ER+/PR+model (change in age-adjusted AUC = 0.020, p <
0.001) as well as the ER+/PR- model (change in age-adjusted AUC = 0.012, p =
0.007). Adolescent somatotype, predicted percent MD, breastfeeding, and vegetable
intake improved the ER-/PR- model (change in AUC = 0.031, p < 0.0001). The RR of
ER-/PR- disease for 5 vegetable servings/day increase was 0.83 (95% CI 0.70,
0.99), while the RR for every 12 months of breastfeeding was 0.88 (95% CI 0.77,
1.01). Physical activity did not improve risk classification in any model.
CONCLUSION: Adolescent somatotype and predicted percent MD significantly improved
breast cancer risk classification using the Rosner-Colditz model. Further, risk
factors specific to ER- disease, such as breastfeeding and vegetable intake, may
also help improve risk prediction of this aggressive subtype.
PMID- 28702897
TI - Hereditary diffuse gastric cancer and lynch syndromes in a BRCA1/2 negative
breast cancer patient.
AB - INTRODUCTION: Genetic counseling and testing is recommended for women with a
personal and/or family history of breast and other cancers (ovarian, pancreatic,
male breast and others). Mutations in the BRCA1 and BRCA2 genes (BRCA1/2) are the
most common causes of hereditary breast and ovarian cancer. Additional genetic
counseling and testing with a multi-gene panel may be considered in breast cancer
patients who tested negative for mutations in these two genes. In about 11% of
BRCA1/2-negative patients, further genetic testing reveals pathogenic mutations
in other high or moderate cancer risk genes. In 0.2% of cases, an individual may
carry pathogenic mutations in more than one high penetrance gene (a double
heterozygote). Finding one or more pathogenic mutations is important for cancer
prevention in patients and/or their families. CASE PRESENTATION: Here we present
a case of a breast cancer patient who did not have a pathogenic mutation in
BRCA1/2 and had a family history of breast and stomach cancers. On an additional
multi-gene panel testing, she was found to carry pathogenic mutations in the CDH1
and PMS2 genes, which cause Hereditary Diffuse Gastric Cancer and Lynch
syndromes, respectively. To our knowledge, this is the first description of such
a double heterozygote. DISCUSSION: Clinical manifestations, genetics, and
management of both syndromes are reviewed, including prophylactic surgery and
screening for unaffected family members. Management challenges for a mutation
carrier with advanced breast cancer are discussed. Our case supports the clinical
utility of additional multi-gene panel testing for breast cancer patients who do
not have a pathogenic mutation in BRCA1/2 genes.
PMID- 28702898
TI - Perioperative depression or anxiety and postoperative mortality in cardiac
surgery: a systematic review and meta-analysis.
AB - We performed a systematic review and meta-analysis to determine whether
perioperative depression and anxiety are associated with increased postoperative
mortality in patients undergoing cardiac surgery. MEDLINE and EMBASE were
searched through January 2017 using PubMed and OVID, to identify observational
studies enrolling patients undergoing cardiac surgery and reporting relative risk
estimates (RREs) (including odds, hazard, or mortality ratios) of short term (30
days or in-hospital) and/or late all-cause mortality for patients with versus
without perioperative depression or anxiety. Study-specific estimates were
combined using inverse variance-weighted averages of logarithmic RREs in the
random-effects models. Our search identified 16 eligible studies. In total, the
present meta-analysis included data on 236,595 patients undergoing cardiac
surgery. Pooled analysis demonstrated that perioperative depression was
significantly associated with increased both postoperative early (RRE, 1.44; 95%
confidence interval [CI] 1.01-2.05; p = 0.05) and late mortality (RRE, 1.44; 95%
CI 1.24-1.67; p < 0.0001), and that perioperative anxiety significantly
correlated with increased postoperative late mortality (RRE, 1.81; 95% CI 1.20
2.72; p = 0.004). The relation between anxiety and early mortality was reported
in only one study and not statistically significant. In the association of
depression with late mortality, there was no evidence of significant publication
bias and meta-regression indicated that the effects of depression are not
modulated by the duration of follow-up. In conclusion, perioperative depression
and anxiety may be associated with increased postoperative mortality in patients
undergoing cardiac surgery.
PMID- 28702899
TI - Complex antioxidants in a randomized single-blinded study of memory in seniors.
AB - INTRODUCTION: Oxidative injury to the brain and aging are theoretical co-causes
of Alzheimer's Disease (AD). Amyloid plaques and tangles are then secondary
phenomenon. The preclinical state would then be 'normal' elderly. METHODS: A
potent complex antioxidant (antiOx) was tested against a popular one-a-day
multivitamin (mV) in a randomized single blind design in 'normal' senior subjects
over 6 months. Memory testing was done at baseline, 1, 3, and 6 months. The
generalized estimating equation (GEE) approach was used to compare the change
score of NLT100 and 20WR between two groups over time. RESULTS: Analysis of the
antiOx group (30 subjects) demonstrated significant improvement in declarative
memory (change score for NLT100 at month 6 = 6.36 p < 0.0001) and working memory
(change score for 20WR at month 6 = 3.23, p < 0.0001). A change-score analysis
over 6 months suggests possible neurogenesis in the antiOx group. The mV group
(33 subjects) had a change score of the NLT100 and 20WR on the sixth month of
2.20 and 0.32 (p = 0.07, 0.35). CONCLUSIONS: A complex antioxidant blend, sold as
an over-the-counter (OTC) supplement, can improve memory in elder subjects.
Antioxidants may be beneficial in AD and other neurodegerative diseases.
PMID- 28702900
TI - Selected In-Season Nutritional Strategies to Enhance Recovery for Team Sport
Athletes: A Practical Overview.
AB - Team sport athletes face a variety of nutritional challenges related to recovery
during the competitive season. The purpose of this article is to review nutrition
strategies related to muscle regeneration, glycogen restoration, fatigue,
physical and immune health, and preparation for subsequent training bouts and
competitions. Given the limited opportunities to recover between training bouts
and games throughout the competitive season, athletes must be deliberate in their
recovery strategy. Foundational components of recovery related to protein,
carbohydrates, and fluid have been extensively reviewed and accepted.
Micronutrients and supplements that may be efficacious for promoting recovery
include vitamin D, omega-3 polyunsaturated fatty acids, creatine,
collagen/vitamin C, and antioxidants. Curcumin and bromelain may also provide a
recovery benefit during the competitive season but future research is warranted
prior to incorporating supplemental dosages into the athlete's diet. Air travel
poses nutritional challenges related to nutrient timing and quality.
Incorporating strategies to consume efficacious micronutrients and ingredients is
necessary to support athlete recovery in season.
PMID- 28702901
TI - Implications of Impaired Endurance Performance following Single Bouts of
Resistance Training: An Alternate Concurrent Training Perspective.
AB - A single bout of resistance training induces residual fatigue, which may impair
performance during subsequent endurance training if inadequate recovery is
allowed. From a concurrent training standpoint, such carry-over effects of
fatigue from a resistance training session may impair the quality of a subsequent
endurance training session for several hours to days with inadequate recovery.
The proposed mechanisms of this phenomenon include: (1) impaired neural
recruitment patterns; (2) reduced movement efficiency due to alteration in
kinematics during endurance exercise and increased energy expenditure; (3)
increased muscle soreness; and (4) reduced muscle glycogen. If endurance training
quality is consistently compromised during the course of a specific concurrent
training program, optimal endurance development may be limited. Whilst the link
between acute responses of training and subsequent training adaptation has not
been fully established, there is some evidence suggesting that cumulative effects
of fatigue may contribute to limiting optimal endurance development. Thus, the
current review will (1) explore cross-sectional studies that have reported
impaired endurance performance following a single, or multiple bouts, of
resistance training; (2) identify the potential impact of fatigue on chronic
endurance development; (3) describe the implications of fatigue on the quality of
endurance training sessions during concurrent training, and (4) explain the
mechanisms contributing to resistance training-induced attenuation on endurance
performance from neurological, biomechanical and metabolic standpoints.
Increasing the awareness of resistance training-induced fatigue may encourage
coaches to consider modulating concurrent training variables (e.g., order of
training mode, between-mode recovery period, training intensity, etc.) to limit
the carry-over effects of fatigue from resistance to endurance training sessions.
PMID- 28702903
TI - Erratum to: Budesonide.
PMID- 28702902
TI - Oxygenation Status in Chronic Leg Ulcer After Topical Hemoglobin Application May
Act as a Surrogate Marker to Find the Best Treatment Strategy and to Avoid
Ineffective Conservative Long-term Therapy.
AB - PURPOSE: Chronic leg ulcers can be a challenge to treat and long-term therapy a
significant cost factor in western public health budgets. Objective wound
assessment assays enabling selection of appropriate wound therapy regimes would
be desirable. Oxygenation status in ulcer tissue has obtained increased attention
as a relevant factor in wound healing. To increase oxygenation in wounds, a
topical hemoglobin spray was developed. Although favorable results have been
noted, the link between clinical efficacy and the mode of action has not been
demonstrated. The aims were to determine if changes in tissue oxygenation can be
measured after topical application of hemoglobin on chronic wounds and to
evaluate the findings in terms of therapy strategies. PROCEDURES: Photoacoustic
imaging was used to measure the local oxygen saturation (StO2) in leg ulcers
before and after hemoglobin spray treatment. Sclerosis of the leg ulcers was
histopathologically graded and the change in wound size was documented in a
follow-up examination. RESULTS: Measuring 49 patients, an increase in StO2 after
topical hemoglobin application from on average 66.1 to 71 % (p = 0.017) after 20
min was observed. Depending on the increase in StO2 (>10 % or <10 %) patients
were stratified into a Responder and a Non-Responder group. Wound size
significantly decreased in the Responder Group (p = 0.001), while no significant
difference in the Non-Responder group (p = 0.950) was noted. CONCLUSION: Our
findings suggest that the likelihood of wound healing under conservative therapy
can be predicted by measuring changes in StO2 after topical hemoglobin
application. This assay may reduce treatment time and costs by avoiding
ineffective conservative long-term therapy. TRIAL REGISTRATION: German Clinical
Trials Register: DRKS00005993.
PMID- 28702904
TI - Formation of brominated and chlorinated dioxins and its prevention during a pilot
test of mechanochemical treatment of PCB and PBDE contaminated soil.
AB - The destruction of persistent organic pollutants (POPs) is a large challenge in
particular in developing and emerging economies. To date, a detailed assessment
of non-combustion technologies with respect to formation of dioxins is lacking.
In this study, an assessment of mechanochemical (MC) destruction technology for
polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) in
contaminated soil remediation was conducted. Actual applied conditions of pilot
scale MC POPs destruction process indicates that the temperature increase inside
the ball mills has the potential to form high levels of toxic polybrominated and
polychlorinated dibenzo-p-dioxins and dibenzofurans (PXDD/Fs) when dioxin
precursors are present. Therefore, the MC technology was modified for treatment
of the PCB and PBDE containing soil including an efficient cooling system which
could prevent the formation of PXDD/F during the destruction of PCBs and PBDEs.
This is likely relevant for all contaminated soils containing relevant dioxin
precursor and need to be considered for treatment of soils with MC and probably
other non-combustion technologies. Graphical abstract ?.
PMID- 28702905
TI - Assessment of biofilm changes and concentration-depth profiles during
arsenopyrite oxidation by Acidithiobacillus thiooxidans.
AB - Biofilm formation and evolution are key factors to consider to better understand
the kinetics of arsenopyrite biooxidation. Chemical and surface analyses were
carried out using Raman spectroscopy, scanning electron microscopy (SEM),
confocal laser scanning microscopy (CLSM), glow discharge spectroscopy (GDS), and
protein analysis (i.e., quantification) in order to evaluate the formation of
intermediate secondary compounds and any significant changes arising in the
biofilm structure of Acidithiobacillus thiooxidans during a 120-h period of
biooxidation. Results show that the biofilm first evolves from a low cell density
structure (1 to 12 h) into a formation of microcolonies (24 to 120 h) and then
finally becomes enclosed by a secondary compound matrix that includes pyrite
(FeS2)-like, S n2-/S0, and As2S3 compounds, as shown by Raman and SEM-EDS. GDS
analyses (concentration-depth profiles, i.e., 12 h) indicate significant
differences for depth speciation between abiotic control and biooxidized
surfaces, thus providing a quantitative assessment of surface-bulk changes across
samples (i.e. reactivity and /or structure-activity relationship). Respectively,
quantitative protein analyses and CLSM analyses suggest variations in the type of
extracellular protein expressed and changes in the biofilm structure from
hydrophilic (i.e., exopolysaccharides) to hydrophobic (i.e., lipids) due to
arsenopyrite and cell interactions during the 120-h period of biooxidation. We
suggest feasible environmental and industrial implications for arsenopyrite
biooxidation based on the findings of this study.
PMID- 28702906
TI - Physiological and ultrastructural effects of acute ozone fumigation in the lichen
Xanthoria parietina: the role of parietin and hydration state.
AB - The physiological and ultrastructural effects induced by acute exposure to ozone
(O3) were investigated in the lichen Xanthoria parietina. Our working hypothesis
was that parietin content and hydration of the thalli may play a role in the
modulation of the effects of O3 exposure. Four batches of X. parietina samples,
dry and wet, with (P+) and without (P-) parietin, were fumigated for 1 h with 3
ppm O3. The effects of O3 were assessed immediately after the fumigation and
after one week of recovery under controlled conditions. O3 fumigation caused
physiological and ultrastructural impairment both to the photobiont and the
mycobiont, irrespective if samples were fumigated wet or dry, and P+ or P-.
However, one week after fumigation, a recovery was observed in P+ samples for the
photobiont and in dry samples for the mycobiont. We suggest that the hydration
state may play a major role in determining the severity of the damage, while the
presence of parietin may promote the recovery. Our results provide physiological
and ultrastructural basis to explain the ecological insensitivity of lichens to
high environmental levels of ozone occurring during dry Mediterranean summers.
PMID- 28702907
TI - Vascular plants as ecological indicators of metals in alpine vegetation
(Karkonosze, SW Poland).
AB - Calluna vulgaris, Carex rigida, Deschampsia flexuosa, Nardus stricta and
Vaccinium myrtillus are abundant in the vegetation of mountainous areas in
Northern and Central Europe. Knowledge of their ability to accumulate increased
amounts of metals could be useful in the evaluation of environmental pollution in
the alpine tundra of high mountains. Additionally, this investigation may
contribute to understanding the rate and direction of recent vegetation change in
Karkonosze and similar types of environments. Our investigation revealed that
Carex rigida, C. vulgaris and V. myrtillus contain excessive Mn concentrations in
shoots with the highest BF for this element compared to the BFs of other
elements. C. rigida, with Cu, Mn and Zn concentrations exceeding the toxicity
thresholds for plants, seems to be the best metal phytoaccumulator for Nardus
stricta grasslands Carici (rigidae)-Nardetum (CrN) and alpine heathlands Carici
(rigidae)-Festucetum airoidis (CrFa) associations in the Karkonosze. Based on
relevant BFs >1, it can be stated that the following plant available metals were
transferred to shoots: Cu, Mn and Ni by C. vulgaris; Cd, Cu, Mn, Ni and Zn by C.
rigida; Cd, Cu, Mn, Ni and Zn by D. flexuosa; Cu, Mn, Ni and Zn by N. stricta and
Cu, Mn and Zn by V. myrtillus.
PMID- 28702908
TI - Water quality and health in northern Canada: stored drinking water and acute
gastrointestinal illness in Labrador Inuit.
AB - One of the highest self-reported incidence rates of acute gastrointestinal
illness (AGI) in the global peer-reviewed literature occurs in Inuit communities
in the Canadian Arctic. This high incidence of illness could be due, in part, to
the consumption of contaminated water, as many northern communities face
challenges related to the quality of municipal drinking water. Furthermore, many
Inuit store drinking water in containers in the home, which could increase the
risk of contamination between source and point-of-use (i.e., water
recontamination during storage). To examine this risk, this research
characterized drinking water collection and storage practices, identified
potential risk factors for water contamination between source and point-of-use,
and examined possible associations between drinking water contamination and self
reported AGI in the Inuit community of Rigolet, Canada. The study included a
cross-sectional census survey that captured data on types of drinking water used,
household practices related to drinking water (e.g., how it was collected and
stored), physical characteristics of water storage containers, and self-reported
AGI. Additionally, water samples were collected from all identified drinking
water containers in homes and analyzed for presence of Escherichia coli and total
coliforms. Despite municipally treated tap water being available in all homes,
77.6% of households had alternative sources of drinking water stored in
containers, and of these containers, 25.2% tested positive for total coliforms.
The use of transfer devices and water dippers (i.e., smaller bowls or measuring
cups) for the collection and retrieval of water from containers were both
significantly associated with increased odds of total coliform presence in stored
water (ORtransfer device = 3.4, 95% CI 1.2-11.7; ORdipper = 13.4, 95% CI 3.8
47.1). Twenty-eight-day period prevalence of self-reported AGI during the month
before the survey was 17.2% (95% CI 13.0-22.5), which yielded an annual incidence
rate of 2.4 cases per person per year (95% CI 1.8-3.1); no water-related risk
factors were significantly associated with AGI. Considering the high prevalence
of, and risk factors associated with, indicator bacteria in drinking water stored
in containers, potential exposure to waterborne pathogens may be minimized
through interventions at the household level.
PMID- 28702909
TI - Lignocellulosic biowastes as carrier material and slow release electron donor for
sulphidogenesis of wastewater in an inverse fluidized bed bioreactor.
AB - Industrial wastewaters containing high concentrations of sulphate, such as those
generated by mining, metallurgical and mineral processing industries, require
electron donor for biological sulfidogenesis. In this study, five types of
lignocellulosic biowastes were characterized as potential low-cost slow release
electron donors for application in a continuously operated sulphidogenic inverse
fluidized bed bioreactor (IFBB). Among them, natural scourer and cork were
selected due to their high composition of volatile solids (VS), viz. 89.1 and
96.3%, respectively. Experiments were performed in batch (47 days) and in an IFBB
(49 days) using synthetic sulphate-rich wastewater. In batch, the scourer gave
higher sulphate reduction rates (67.7 mg SO42- L-1 day-1) in comparison to cork
(12.1 mg SO42- L-1 day-1), achieving >82% sulphate reduction efficiencies. In the
IFBB packed with the natural scourer, the average sulphate reduction efficiency
was 24 (+/-17)%, while the volumetric sulphate reduction rate was 167 (+/-117) mg
SO42- L-1 day-1. The long incubation time in the batch experiments (47 days)
allowed higher sulphate reduction efficiencies in comparison to the short
hydraulic retention time (24 h) in the IFBB. This suggests the hydrolysis
fermentation was the rate-limiting step and the electron donor supply (through
hydrolysis of the lignocellulosic biowaste) was limiting the sulphate reduction.
Lignocellulose as carrier material and slow release electron donor for
sulphidogenesis.
PMID- 28702910
TI - A novel biocoagulant agent from mushroom chitosan as water and wastewater
therapy.
AB - A new commercial cationic polyelectrolyte chitosan (CM), obtained from the waste
of mushroom production, was examined using models of water and wastewater namely
kaolin and palm oil mill effluent (pome). As it is biocompatible, widely
available, and economically feasible, chitosan mushroom has high potential to be
a suitable replacement for alum. Also, it can be a promising alternative to
chitosan obtained traditionally from Crustaceans due to its higher zeta potential
and homogeneity based on the raw material required for its production. A wide
range of coagulant dose (5-60 mg l-1) and wastewater pH (2-12) were taken into
account to find the optimal conditions of coagulation. The optimal doses are 10
and 20 mg l-1 at best pH (11 and 3) when treated with kaolin and palm oil mill
effluent, respectively, while 1200 mg l-1 of alum was not enough to reach the
efficiency of chitosan mushroom. On the other hand, the optimum dose of chitosan
mushroom (20 mg l-1) at pH 3 of pome produced (75, 73, and 98%) removal of
chemical oxygen demand (COD), biological oxygen demand (BOD), and total suspended
solids (TSS), respectively. The significant potential of chitosan mushroom was
proved by zeta potential measurement. Indeed, it possesses the highest zeta
potential (+70 mV) as compared to the traditional chitosan produced from
crustaceans. In short, chitosan mushroom as a biocoagulant is eco-friendly and it
enhances water quality that meets the requirements of environmental
conservatives.
PMID- 28702911
TI - Kinetics of 210Po accumulation in moss body profiles.
AB - Radionuclide concentration analysis of total moss bodies often gave relatively
different results than a separate analysis of each different morphological part
of the same sample. The dynamics of the transfer of metals by dust uplifted from
the soil and another approach, based on the diffusion of the two radionuclides to
the moss, have been analyzed. In the proposed model, short- and long-term
approaches have been applied. Each part of a moss's profile can show different
radionuclides accumulation ability, including both 210Pb and 210Po isotopes. A
first-order kinetic model has been used for 210Po and 210Pb transport between
three body components of mosses. This mathematical approach has been applied for
210Po activity concentration in the air estimation. For relatively clean deep
forest region, calculated concentrations were from 17.2 to 43.8 MUBqm-3, while
for urban air concentrations were higher from 49.1 to 104.9 MUBqm-3.
PMID- 28702912
TI - The sugarcane herbicide ametryn induces oxidative stress and developmental
abnormalities in zebrafish embryos.
AB - Ametryn (AMT) is one of the most widely used herbicides in tropical sugarcane
crops, the main culture of Sao Paulo State, Brazil. It is known as a diffuse
pollutant, being found in surface water and sediment of water bodies adjacent to
the crop fields. In the present study, the toxicity of AMT to zebrafish (Danio
rerio) embryos was evaluated using developmental and biochemical endpoints. At
the biochemical level, lactate dehydrogenase responded at the lowest
concentration tested (4 MUg L-1) indicating a high demand of energy required to
cope with the stress condition. Antioxidant enzyme levels were changed at
intermediate/high concentrations while oxidative damage (lipid peroxidation) was
observed at the last concentration tested (10 mg L-1). This suggests that, like
for other herbicides from the triazine group, oxidative stress is a major pathway
of toxicity for AMT. Several developmental effects such as oedemas and tail
deformities were also observed. The 96 h-EC50 values calculated for different
developmental parameters were between 17 and 29 mg L-1. AMT also affected
hatching (96 h-EC50 = 22.5 mg L-1) and positioning in the water column (96 h-EC50
= 13.2 mg L-1). In a previous work of the group, lethal toxicity of AMT showed to
be much higher to adults than to embryos. However, in the present work, sublethal
endpoints assessed suggest that important effects are observed at lower
concentrations, improving the sensitivity of the embryo test. Moreover, in this
work, sublethal effects were observed for concentrations in the same range as the
ones found in the environment, and thus, given that this chemical is widely used
in tropical fields, a refined evaluation of risk should be performed based on the
monitoring of sublethal and long-term parameters and considering mixture
scenarios.
PMID- 28702913
TI - Time series analysis of ambient air pollution effects on daily mortality.
AB - Although the growths of ambient pollutants have been attracting public concern,
the characteristic of the associations between air pollutants and mortality
remains elusive. Time series analysis with a generalized additive model was
performed to estimate the associations between ambient air pollutants and
mortality outcomes in Shenzhen City for the period of 2012-2014. The results
showed that nitrogen dioxide (NO2)-induced excess risks (ER) of total non
accidental mortality and cardiovascular mortality were significantly increased
(6.05% (95% CI 3.38%, 8.78%); 6.88% (95% CI 2.98%, 10.93%), respectively) in
interquartile range (IQR) increase analysis. Also, these associations were
strengthened after adjusting for other pollutants. Moreover, similar associations
were estimated for sulfur dioxide (SO2), particulate matter with an aerodynamic
diameter of <10 MUm (PM10), and total non-accidental mortality. There were
significant higher ERs of associations between PM10 and mortality for men than
women; while there were significant higher ERs of associations between PM10/NO2
and mortality for elders (65 or elder) than youngers (64 or younger). Season
analyses showed that associations between NO2 and total non-accidental mortality
were more pronounced in hot seasons than in warm seasons. Taken together, NO2 was
positively associated with total non-accidental mortality and cardiovascular
mortality in Shenzhen even when the concentrations were below the ambient air
quality standard. Policy measures should aim at reducing residents' exposure to
anthropogenic NO2 emissions.
PMID- 28702914
TI - Bactericidal activity of Cu-, Zn-, and Ag-containing zeolites toward Escherichia
coli isolates.
AB - Two types of zeolites-natural clinoptilolite (NZ) and synthetic zeolite A (A)
were enriched with approx. 0.25 mmol of Cu(II), Zn(II), or Ag(I) ions, and the
obtained materials (M-Z) were tested against three different isolates of
Escherichia coli. Two isolates were environmental isolates from waters in Serbia
whereas the third one was DSM 498. Antibacterial activity was studied in
different water media-nutrient-rich media (peptone water), water from Sava Lake,
and commercially available spring water. The Ag-containing zeolites showed
bactericidal activity in the nutrient-rich peptone water after 1 h of contact. Cu
and Zn-containing zeolites showed bactericidal activity in real water samples.
Antibacterial activity of the M-Z decreases in all three examined water media in
the following order: Ag-NZ ~ Ag-A > Cu-NZ ~ Cu-A > Zn-NZ >>> Zn-A, suggesting
that mainly the metal type and not the zeolite type have a role in the
antibacterial activity. Leaching experiments showed small amounts of the leached
Cu(II) and Zn(II) ions, indicating that the antibacterial activity is not due to
the metal ions but should be attributed to the M-Z itself. However, leached
amounts of Ag(I) from Ag-NZ and Ag-A in peptone water indicate that the released
Ag(I) could be mainly responsible for the bactericidal effect of the Ag(I)
containing zeolites. Since no loss of cellular material was found, the
antibacterial activity is not attributed to cytoplasmic membrane damage.
PMID- 28702915
TI - Soy molasses as a fermentation substrate for the production of biosurfactant
using Pseudomonas aeruginosa ATCC 10145.
AB - Soy molasses is a product co-generated during soybean processing that has high
production and low commercial value. Its use has great potential in fermentative
processes due to the high concentration of carbohydrates, lipids and proteins.
This study investigated the use of Pseudomonas aeruginosa to produce
biosurfactants in a soy molasses-based fermentation medium. A central composite
design (CCD) was prepared with two variables and three replicates at the central
point to optimize the production of biosurfactant. The concentration of soy
molasses had values between 29.3 and 170.7 g/L and the initial concentration of
microorganism varied between 0.2 and 5.8 g/L. All the experiments were performed
in duplicate on a shaker table at 30.0 +/- 1.0 degrees C and 120 rpm for 72 h
with samples taken every 12 h. Thus, to validate the experiments, the values of
120 g/L for the initial concentration of soy molasses and 4 g/L for the initial
concentration of microorganisms were used. In response, the following values were
obtained at 48 h of fermentation: surface tension of 31.9 dyne/cm, emulsifying
index of 97.4%, biomass concentration of 11.5 g/L, rhamnose concentration of 6.9
g/L and biosurfactant concentration of 11.70 g/L. Further analysis was carried
out for critical micelle concentration (CMC) which was obtained at approximately
80 mg/L. The bands found in Fourier transform infrared spectroscopy analysis had
characteristic glycolipids as reported in the literature. These values show a
great potential for biosurfactant production using soy molasses as a substrate
and bacteria of the species P. aeruginosa.
PMID- 28702916
TI - Risk assessment of heavy metals in soil of Tongnan District (Southwest China):
evidence from multiple indices with high-spatial-resolution sampling.
AB - Assessment of heavy metal (HM) pollution in soil is critical for human health,
ecological remediation, and soil conservation. In this study, statistical
analyses and geochemical approaches such as enrichment factor (EF), the index of
geoaccumulation (Igeo), and potential ecological risk index (RI) were used for
characterization and risk assessment of soil HMs through a high-spatial
resolution 385 samples from Tongnan District, an important agricultural practice
area in Chongqing Municipality in Southwest China. Igeo and EF indicated that Hg
and Cd could be considered as low and moderate polluted, respectively, and others
HMs were not a major concern. Comprehensive ecological risk information further
demonstrated that the HMs have caused a moderate risk. Principal component
analysis (PCA) extracted two principal components (PCs) with eigenvalue >1
explaining about 66.1% of the total variance in the HM data sets, demonstrating
major source of anthropogenic activity, phosphate fertilizers, vehicle, and
pesticides. These multi-index methods have the capacity of HM assessment in soil,
which are useful for soil conservation and ecological remediation.
PMID- 28702917
TI - Occurrence and risk assessment of antidepressants in Huangpu River of Shanghai,
China.
AB - Antidepressants are gaining public attention because of increasing reports of
their occurrence in environment and their potential impact on ecosystems and
human health. Continuous input of pharmaceuticals into rivers, through
psychiatric hospital or wastewater treatment plant (WWTPs) effluent, may cause
adverse effects on the aquatic ecosystems of the receiving water bodies. This
work investigates the occurrence and sources of 8 antidepressants in main stream
and tributaries of Huangpu River in Shanghai. The detected concentrations of the
selected antidepressants ranged from low nanogram per liter to 42.9 ng L-1
(fluoxetine) in main stream and ranged from low nanogram per liter to 33.7 ng L-1
(fluoxetine) in tributaries. To study the effect of hospital or wastewater
treatment plants (WWTPs) on environment, the upstream and downstream samples were
analyzed. Generally, antidepressants had greater concentrations in downstream
than that in upstream of the WWTPs or hospitals. It is suggesting that WWTPs and
hospitals may introduce pollution into water environment. A preliminary risk
assessment was conducted: none of the eight target compounds yielded risk
quotient (RQ) values more than 0.1, thus indicating that no adverse effect is
expected in water environment. These results will provide background data for
future antidepressants pollution control and management in Shanghai, China.
PMID- 28702918
TI - Assessment of potential health risk of fluoride consumption through rice, pulses,
and vegetables in addition to consumption of fluoride-contaminated drinking water
of West Bengal, India.
AB - A study was conducted in fluoride-affected Bankura and Purulia districts of West
Bengal to assess the potential health risk from fluoride exposure among children,
teenagers, and adults due to consumption of rice, pulses, and vegetables in
addition to drinking water and incidental ingestion of soil by children. Higher
mean fluoride contents (13-63 mg/kg dry weight) were observed in radish, carrot,
onion bulb, brinjal, potato tuber, cauliflower, cabbage, coriander, and pigeon
pea. The combined influence of rice, pulses, and vegetables to cumulative
estimated daily intake (EDI) of fluoride for the studied population was found to
be 9.5-16%. Results also showed that intake of ivy gourd, broad beans, rice,
turnip, fenugreek leaves, mustard, spinach, and amaranth grown in the study area
is safe at least for time being. The cumulative EDI values of fluoride (0.06-0.19
mg/kg-day) among different age group of people of the study area were evaluated
to be ~104 times higher than those living in the control area; the values for
children (0.19 and 0.52 mg/kg-day for CTE and RME scenarios, respectively) were
also greater than the "Tolerable Upper Intake Level" value of fluoride. The
estimated hazard index (HI) for children (3.2 and 8.7 for CTE and RME scenarios,
respectively) living in the two affected districts reveals that they are at high
risk of developing dental fluorosis due to the consumption of fluoride
contaminated rice, pulses, and vegetables grown in the study area in addition to
the consumption of contaminated drinking water.
PMID- 28702919
TI - Experimental investigation of performance and emissions of a VCR diesel engine
fuelled with n-butanol diesel blends under varying engine parameters.
AB - The continuous rise in the cost of fossil fuels as well as in environmental
pollution has attracted research in the area of clean alternative fuels for
improving the performance and emissions of internal combustion (IC) engines. In
the present work, n-butanol is treated as a bio-fuel and investigations have been
made to evaluate the feasibility of replacing diesel with a suitable n-butanol
diesel blend. In the current research, an experimental investigation was carried
out on a variable compression ratio CI engine with n-butanol-diesel blends (10
25% by volume) to determine the optimum blending ratio and optimum operating
parameters of the engine for reduced emissions. The best results of performance
and emissions were observed for 20% n-butanol-diesel blend (B20) at a higher
compression ratio as compared to diesel while keeping the other parameters
unchanged. The observed deterioration in engine performance was within tolerable
limits. The reductions in smoke, nitrogen oxides (NO x ), and carbon monoxide
(CO) were observed up to 56.52, 17.19, and 30.43%, respectively, for B20 in
comparison to diesel at rated power. However, carbon dioxide (CO2) and
hydrocarbons (HC) were found to be higher by 17.58 and 15.78%, respectively, for
B20. It is concluded that n-butanol-diesel blend would be a potential fuel to
control emissions from diesel engines. Graphical abstract ?.
PMID- 28702920
TI - Erratum to: Association Study between Coronary Artery Disease and rs1333049
Polymorphism at 9p21.3 Locus in Italian Population.
PMID- 28702921
TI - ACL Return to Sport Guidelines and Criteria.
AB - PURPOSE OF REVIEW: Because of the epidemiological incidence of anterior cruciate
ligament (ACL) injuries, the high reinjury rates that occur when returning back
to sports, the actual number of patients that return to the same premorbid level
of competition, the high incidence of osteoarthritis at 5-10-year follow-ups, and
the effects on the long-term health of the knee and the quality of life for the
patient, individualizing the return to sports after ACL reconstruction (ACL-R) is
critical. However, one of the challenging but unsolved dilemmas is what criteria
and clinical decision making should be used to return an athlete back to sports
following an ACL-R. This article describes an example of a functional testing
algorithm (FTA) as one method for clinical decision making based on quantitative
and qualitative testing and assessment utilized to make informed decisions to
return an athlete to their sports safely and without compromised performance. The
methods were a review of the best current evidence to support a FTA. RECENT
FINDINGS: In order to evaluate all the complicated domains of the clinical
decision making for individualizing the return to sports after ACL-R, numerous
assessments need to be performed including the biopsychosocial concepts,
impairment testing, strength and power testing, functional testing, and patient
reported outcomes (PROs). The optimum criteria to use for individualizing the
return to sports after ACL-R remain elusive. However, since this decision needs
to be made on a regular basis with the safety and performance factors of the
patient involved, this FTA provides one method of quantitatively and
qualitatively making the decisions. Admittedly, there is no predictive validity
of this system, but it does provide practical guidelines to facilitate the
clinical decision making process for return to sports. The clinical decision to
return an athlete back into competition has significant implications ranging from
the safety of the athlete, to performance factors and actual litigation issues.
By using a multifactorial FTA, such as the one described, provides quantitative
and qualitatively criteria to make an informed decision in the best interests of
the athlete.
PMID- 28702922
TI - Public expenditure and healthcare utilization: the case of reproductive health
care in India.
AB - An important reason for public intervention in health in developing countries is
to address the issue of accessibility. However, numerous studies have found
inconclusive evidence of the effect of public expenditure on health outcomes.
Here, I revisit the debate by examining the effect of public expenditure on the
use of health services, which is an important link between expenditure and
outcomes. I use data from two recent waves of the National Family Health Survey
of India to study the role of public expenditure on the use of healthcare
services during pregnancy and childbirth. India has high state-level variations
in the use of prenatal care and delivery by skilled personnel as well as levels
of public expenditure. I exploit the variation in public expenditure to identify
its effect on the use of healthcare services, controlling for other confounding
factors. The results show a significant effect of public expenditure at the state
level on the use of both prenatal and delivery care at the individual level.
Also, there is no evidence of public expenditure crowding out private
expenditure. Further, there is strong evidence that public expenditure reaches
the desired targets. The results highlight the positive implications of raising
public expenditure for healthcare use of pregnancy and childbirth services in the
Indian context.
PMID- 28702923
TI - Right ventricular perfusion: Do we need additional evidence or just a simple
methodology?
PMID- 28702924
TI - Impact and Impact Factor.
PMID- 28702925
TI - Utilization of Cervical Cancer Screening Among Hispanic Immigrant Women in
Coastal South Carolina.
AB - OBJECTIVES: This study aims to examine prevalence and correlates of cervical
cancer screening utilization and adherence among a growing population of Hispanic
immigrant women in coastal South Carolina. METHODS: We conducted a cross
sectional survey of 196 women to assess recency of screening and hypothesized
study predictors (health status, beliefs, self-efficacy, having a regular
provider, barriers to screening, and trust in providers). Multiple ordinal
logistic regressions identified final covariates which would predict recency of
screening. RESULTS: Approximately 84% of women were up-to-date with their Pap
tests and 47% had received a Pap test in the previous year. In the adjusted
analyses, having a regular provider and having a chronic medical condition were
significantly associated with recency of Pap test. CONCLUSIONS: Differences in
cervical cancer screening for participants were partially explained by
psychosocial factors, health status, and individual and structural barriers to
healthcare.
PMID- 28702926
TI - The stability evaluation of mesenchymal stem cells differentiation toward
endothelial cells by chemical and mechanical stimulation.
AB - Adipose-derived mesenchymal stem cells (ADSCs) are adult multipotent cells able
to differentiate into several cell lineages. Vascular endothelial growth factor
(VEGF) and the shear stress associated with blood flow are considered as the most
important chemical and mechanical cues that play major roles in endothelial
differentiation. However, the stability of endothelial-specific gene expression
has not been completely addressed yet. ADSCs in passage 3 were cultured inside
the tubular silicon tubes and then exposed to VEGF or shear stress produced in a
perfusion bioreactor. To investigate the differentiation, the expression levels
of Flk-1, von Willebrand factor (vWF), and vascular endothelial-cadherin (VE
cadherin) were studied using Real-Time PCR. For studying the endothelial
differentiation stability, mRNA levels of the genes were evaluated in certain
time intervals after completion of the tests so as to determine whether the
expression level of each gene in different time points was stable and remained
constant or not. Application of VEGF and shear stress caused an elevation in
endothelial cells' specific genes. Although there are some changes following the
days after application of mechanical and chemical stimuli, the gene expression
results depicted significantly higher gene expression between sequential
chemically and mechanically incited groups. In conclusion, stress alone can be a
differentiating factor, by itself. Our results verified the efficient stable
differentiation ability of the chemical and mechanical factors.
PMID- 28702927
TI - 3D Boolean operations in virtual surgical planning.
AB - PURPOSE: Boolean operations in computer-aided design or computer graphics are a
set of operations (e.g. intersection, union, subtraction) between two objects
(e.g. a patient model and an implant model) that are important in performing
accurate and reproducible virtual surgical planning. This requires accurate and
robust techniques that can handle various types of data, such as a surface
extracted from volumetric data, synthetic models, and 3D scan data. METHODS: This
article compares the performance of the proposed method (Boolean operations by a
robust, exact, and simple method between two colliding shells (BORES)) and an
existing method based on the Visualization Toolkit (VTK). RESULTS: In all tests
presented in this article, BORES could handle complex configurations as well as
report impossible configurations of the input. In contrast, the VTK
implementations were unstable, do not deal with singular edges and coplanar
collisions, and have created several defects. CONCLUSIONS: The proposed method of
Boolean operations, BORES, is efficient and appropriate for virtual surgical
planning. Moreover, it is simple and easy to implement. In future work, we will
extend the proposed method to handle non-colliding components.
PMID- 28702928
TI - Underuse of Oral Anticoagulants and Inappropriate Prescription of Antiplatelet
Therapy in Older Inpatients with Atrial Fibrillation.
AB - BACKGROUND: Several studies have shown that the prescription of antiplatelet
therapy (APT) is associated with an increased risk of oral anticoagulant (OAC)
underuse in patients aged 75 years and over with atrial fibrillation (AF). An
associated atheromatous disease may be the underlying reason for APT
prescription. The objective of the study was to determine whether the association
between underuse of OAC and APT prescription was explained by the presence of an
atheromatous disease. METHODS AND RESULTS: We performed a retrospective,
observational, single-centre study between 2009 and 2013 based on administrative
data. Patients aged 75 years and over with non-valvular AF were identified in a
database of 72,090 hospital stays. Prescriptions of anti-thrombotic medications
and their association with the presence of atheromatous disease were evaluated by
the mean of a logistic regression. A total of 2034 hospital stays were included
(mean age 84.3 +/- 5.2 years). The overall prevalence of known atheromatous
disease was 25.9%. OAC underuse was observed in 58.5% of the stays. In
multivariable analysis, the prescription of an APT was associated with an
increased risk of OAC underuse [odds ratio (OR) 6.85; 95% confidence interval
(CI) 5.50-8.58], independently of the presence of a concomitant known
atheromatous disease (OR 0.78; 95% CI 0.60-1.01). Among the 692 stays with APT
monotherapy (34.0%), 232 (33.5%) displayed an atheromatous disease. CONCLUSIONS:
The underuse of OAC is associated with the prescription of APT in older patients
with AF, regardless of the presence or absence of known atheromatous disease. Our
results suggest that APT is often inappropriately prescribed instead of OAC.
PMID- 28702929
TI - The Mechanism Behind Top-Down UVPD Experiments: Making Sense of Apparent
Contradictions.
AB - Top-down ultraviolet photodissociation (UVPD) allows greater sequence coverage
than any other currently available method, often fracturing the vast majority of
peptide bonds in whole proteins. At the same time, UVPD can be used to dissociate
noncovalent complexes assembled from multiple proteins without breaking any
covalent bonds. Although the utility of these experiments is unquestioned, the
mechanism underlying these seemingly contradictory results has been the subject
of many discussions. Herein, some fundamental considerations of photochemistry
are briefly summarized within the context of a proposed mechanism that
rationalizes the experimental results obtained by UVPD. Considerations for future
instrument design, in terms of wavelength choice and power, are briefly
discussed. Graphical Abstract ?.
PMID- 28702931
TI - Autophagy induced by bovine viral diarrhea virus infection counteracts apoptosis
and innate immune activation.
AB - Bovine viral diarrhea virus (BVDV) is an important pathogen of cattle that plays
a complex role in disease. There are two biotypes of BVDV: non-cytopathic (NCP)
and cytopathic (CP). One strategy that has been used to treat or prevent virus
associated diseases is the modulation of autophagy, which is used by the innate
immune system to defend against viral infection; however, at present, the
interplay between autophagy and BVDV remains unclear. Madin-Darby bovine kidney
cells stably expressing microtubule-associated protein 1 light chain 3B (LC3B)
with green fluorescent protein (GFP) (GFP-LC3-MDBK cells) and autophagy-deficient
MDBKs (shBCN1-MDBK cells) were constructed. Then MDBK, GFP-LC3-MDBK and shBCN1
MDBK cells were infected with CP or NCP BVDV strains. The LC3-II turnover rate
was estimated by western blot, autophagosomes were visualized by confocal
microscopy, and ultrastructural analysis was performed using electron microscopy.
Autophagy flux was observed using chloroquine as an inhibitor of the autophagic
process. The influence of autophagy on BVDV replication and release was
investigated using virus titration, and its effect on cell viability was also
studied. The effect of BVDV-induced autophagy on the survival of BVDV-infected
host cell, cell apoptosis, and interferon (IFN) signalling was studied by flow
cytometric analysis and quantitative RT-(q)PCR using shBCN1-MDBK cells. we found
that infection with either CP or NCP BVDV strains induced steady-state autophagy
in MDBK cells, as evident by the increased number of double- or single-membrane
vesicles, the accumulation of GFP- microtubule-associated protein 1 light chain 3
(LC3) dots, and the conversion of LC3-I (cytosolic) to LC3-II (membrane-bound)
forms. The complete autophagic process was verified by monitoring the LC3-II
turnover ratio, lysosomal delivery, and proteolysis. In addition, we found that
CP and NCP BVDV growth was inhibited in MDBK cells treated with high levels of an
autophagy inducer or inhibitor, or in autophagy deficient-MDBK cells.
Furthermore, our studies also suggested that CP and NCP BVDV infection in
autophagy-knockdown MDBK cells increased apoptotic cell death and enhanced the
expression of the mRNAs for IFN-alpha, Mx1, IFN-beta, and OAS-1 as compared with
control MDBK cells. Our study provides strong evidence that BVDV infection
induces autophagy, which facilitates BVDV replication in MDBK cells and impairs
the innate immune response. These findings might help to illustrate the
pathogenesis of persistent infection caused by BVDV.
PMID- 28702930
TI - Personalized medicine in rheumatology: the paradigm of serum autoantibodies.
AB - The sequencing of the human genome is now well recognized as the starting point
of personalized medicine. Nonetheless, everyone is unique and can develop
different phenotypes of the same disease, despite identical genotypes, as well
illustrated by discordant monozygotic twins. To recognize these differences, one
of the easiest and most familiar examples of biomarkers capable of identifying
and predicting the outcome of patients is represented by serum autoantibodies. In
this review, we will describe the concept of personalized medicine and discuss
the predictive, prognostic and preventive role of antinuclear antibodies (ANA),
anti-citrullinated peptide antibodies (ACPA), rare autoantibodies and anti-drug
antibodies (ADA), to evaluate how these can help to identify different disease
immune phenotypes and to choose the best option for treating and monitoring
rheumatic patients in everyday practice. The importance of ANA resides in the
prediction of clinical manifestations in systemic sclerosis and systemic lupus
erythematosus and their association with malignancies. ACPA have a predictive
role in rheumatoid arthritis, they are associated with the development of a more
aggressive disease, extra-articular manifestations and premature mortality in RA
patients; moreover, they are capable of predicting therapeutic response. Rare
autoantibodies are associated with different disease manifestations and also with
a greater incidence of cancer. The determination of ADA levels may be useful in
patients where the clinical efficacy of TNF-alpha inhibitor has dropped, for the
assessment of a right management. The resulting scenario supports serum
autoantibodies as the cornerstone of personalized medicine in autoimmune
diseases.
PMID- 28702932
TI - Phylogenetic analysis of rabbit haemorrhagic disease virus (RHDV) strains
isolated in Poland.
AB - The aim of this study was to characterise the nucleotide and amino acid sequence
of complete genomes (7.5 kb) from RHDV strains isolated in Poland and estimate
the genetic variability in different elements of the viral RNA. In addition, the
sequence of Polish RHDV isolates isolated from 1988-2015 was compared with the
sequences of other European RHDV, including the RHDVa and RHDV2/RHDVb subtypes.
The complete sequence was developed by the compilation of partial nucleotide
sequences. This sequence consisted of approximately 7428 nucleotides. For
comparison of nucleotide sequences and the development of phylogenetic trees of
Polish RHDV isolates and reference RHDV strains representing the main
phylogenetic groups of classical RHDV, RHDVa and RHDV2 as well as the non
pathogenic rabbit lagovirus RCV, the BLAST software with blastn and MEGA6 with
neighbour-joining method was applied. The complete nucleotide sequence of Polish
isolates of RHDV has also been entered into GenBank. For comparative analysis,
nineteen complete sequences representing the main RHDV genetic types available in
GenBank were used. The results of phylogenetic analysis of Polish RHDV strains
reveals the presence of three classical RHDV genogroups (G2, G4 and G5) and an
RHDVa variant (G6). The oldest RHDV isolates (KGM 1988, PD 1989 and MAL 1994)
belong to genogroup G2. It can be assumed that the elimination of these strains
from the environment probably occurred at the turn of 1994 and 1995. Genogroup G2
was replaced by the phylogenetically younger BLA 1994 and OPO 2004 strains from
genogroup G4, which probably originated from the G3 lineage, represented by the
Italian strains BS89. The last representatives of classical RHDV in Poland are
isolates GSK 1988 and ZD0 2000 from genogroup G5. A single clade contains the
Polish RHDV strains from 2004-2015 (GRZ 2004, KRY 2004, L145 2004, W147 2005, SKO
2013, GLE 2013, RED1 2013, STR 2012, STR2 2013, STR 2014, BIE 2015) identified as
RHDVa, which clustered into genogroup G6, as represented by the RHDV strain
Triptis 1996. All recent isolated RHDV isolates belong exclusively to RHDVa and
no RHDV2 was diagnosed in Poland.
PMID- 28702933
TI - Characterization of Simbu serogroup virus infections in type I interferon
receptor knock-out mice.
AB - In late 2011, Schmallenberg virus (SBV), a novel, arthropod-borne, teratogenic
orthobunyavirus, emerged near the German/Dutch border and thereafter spread
rapidly throughout the continent thereby causing great economic losses in
European livestock. SBV mainly infects ruminants and closely related viruses such
as Sabo virus (SABOV), Simbu virus (SIMBUV) and Sathuperi virus (SATV) have been
isolated from their insect-vectors or putative ruminant hosts. However,
information about their pathogenesis and in vivo studies with SABOV, SIMBUV, and
SATV are scarce. As experimental infections of ruminants are comprehensive and
time-consuming, an SBV small animal model was assessed regarding its suitability
for studying Simbu viruses. Adult type I interferon deficient mice (IFNAR-/-)
were subcutaneously infected with the Simbu serogroup members SABOV, SIMV and
SATV, respectively, and compared to SBV-infected mice. All animals were
clinically, virologically, serologically, and pathologically examined. The
clinical signs were mainly characterised by the loss of body weight and by
paralysis. In blood, and samples from the spleen and brain, high loads of viral
genome were detected using newly developed real-time PCR assays. The most common
histologic lesions included meningo-encephalomyelitis, perivascular cuffing of
lymphocytes and macrophages, neuronal degeneration and gliosis. These lesions
have also been described in foetuses after transplacental infection with SBV. In
situ hybridisation signals were widely distributed in multiple neurons of the
brain and spinal cord in all examined, inoculated mice. In conclusion, IFNAR-/-
mice are a suitable animal model for pathogenesis studies of a broad range of
Simbu serogroup viruses since all the viruses examined displayed a common pattern
of viral organ and tissue distribution in this mouse model.
PMID- 28702934
TI - Paternal Incarceration and Adolescent Social Network Disadvantage.
AB - Previous research has suggested that adolescent peers influence behavior and
provide social support during a critical developmental period, but few studies
have addressed the antecedents of adolescent social networks. Research on the
collateral consequences of incarceration has explored the implications of
parental incarceration for children's behavioral problems, academic achievement,
health, and housing stability, but not their social networks. Using network data
from the National Longitudinal Study of Adolescent Health, I find that
adolescents with recently incarcerated fathers are in socially marginal positions
in their schools and befriend more-marginal peers than other adolescents: their
friends are less advantaged, less academically successful, and more delinquent
than other adolescents' friends. Differences in network outcomes are robust to a
variety of specifications and are consistent across race and gender subgroups.
This study advances the social networks literature by exploring how familial
characteristics can shape adolescent social networks and contributes to the
collateral consequences of incarceration literature by using network analysis to
consider how mass incarceration may promote intergenerational social
marginalization.
PMID- 28702935
TI - Vitamin D3 attenuates cognitive deficits and neuroinflammatory responses in ICV
STZ induced sporadic Alzheimer's disease.
AB - Alzheimer's disease (AD) is a progressive neurodegenerative disorder
characterized by intracellular neurofibrillary tangles and extracellular Abeta
deposition. Growing experimental evidence indicate diverse biological effects of
vitamin D3 including antioxidant, neuroprotective, anti-inflammatory and
cardiovascular benefits. However, the underlying neuroprotective mechanism of
vitamin D3 is still largely elusive. Therefore, the present study was aimed to
investigate the neuroprotective effects of vitamin D3 on ICV-STZ induced sporadic
AD. Our study demonstrated that vitamin D3 pretreatment significantly improved
spatial learning and memory functions and effectively mitigated ICV-STZ mediated
neuronal oxidative stress, mitochondrial aberrations and improved cholinergic
functions. Moreover, vitamin D3 attenuated hippocampal neuroinflammatory response
and reduced neuronal death in cortex and hippocampus. Our findings indicated that
prophylactic vitamin D3 supplementation ameliorated ICV-STZ mediated
neurobehavioral alterations, oxidative stress and neuroinflammation thereby
improving cholinergic functions and reversed degenerative changes in brain. Thus,
our study further provides evidence for its therapeutic supplementation for
various neurodegenerative disorders including AD.
PMID- 28702936
TI - The role of spatial frequency in emotional face classification.
AB - Previous studies with emotional face stimuli have revealed that our ability to
identify different emotional states is dependent on the faces' spatial frequency
content. However, these studies typically only tested a limited number of
emotional states. In the present study, we measured the consistency with which 24
different emotional states are classified when the faces are unfiltered, high-,
or low-pass filtered, using a novel rating method that simultaneously measures
perceived arousal (high to low) and valence (pleasant to unpleasant). The data
reveal that consistent ratings are made for every emotional state independent of
spatial frequency content. We conclude that emotional faces possess both high-
and low-frequency information that can be relied on to facilitate classification.
PMID- 28702938
TI - Evaluation of fermentation kinetics of acid-treated corn cob hydrolysate for
xylose fermentation in the presence of acetic acid by Pichia stipitis.
AB - The efficient utilization of lignocellulosic biomass for ethanol production
depends on the fermentability of the biomass hydrolysate obtained after
pretreatment. In this work we evaluated the kinetics of ethanol production from
xylose using Pichia stipitis in acid-treated corn cob hydrolysate. Acetic acid is
one of the main inhibitors in corn cob hydrolysate that negatively impacts
kinetics of xylose fermentation by P. stipitis. Unstructured kinetic model has
been formulated that describes cell mass growth and ethanol production as a
function of xylose, oxygen, ethanol, and acetic acid concentration. Kinetic
parameters were estimated under different operating conditions affecting xylose
fermentation. This is the first report on kinetics of xylose fermentation by P.
stipitis which includes inhibition of acetic acid on growth and product
formation. In the presence of acetic acid in the hydrolysate, the model
accurately predicted reduction in maximum specific growth rate (from 0.23 to 0.15
h-1) and increase in ethanol yield per unit biomass (from 3 to 6.2 gg-1), which
was also observed during experimental trials. Presence of acetic acid in the
fermentation led to significant reduction in the cell growth rate, reduction in
xylose consumption and ethanol production rate. The developed model accurately
described physiological state of P. stipitis during corn cob hydrolysate
fermentation. Proposed model can be used to predict the influence of xylose,
ethanol, oxygen, and acetic acid concentration on cell growth and ethanol
productivity in industrial fermentation.
PMID- 28702937
TI - Genetic engineering strategies for biotic and abiotic stress tolerance and
quality enhancement in horticultural crops: a comprehensive review.
AB - Genetic engineering technique offers myriads of applications in improvement of
horticultural crops for biotic and abiotic stress tolerance, and produce quality
enhancement. During last two decades, a large number of transgenic horticultural
crops has been developed and more are underway. A number of genes including
natural and synthetic Cry genes, protease inhibitors, trypsin inhibitors and
cystatin genes have been used to incorporate insect and nematode resistance. For
providing protection against fungal and bacterial diseases, various genes like
chitinase, glucanase, osmotin, defensin and pathogenesis-related genes are being
transferred to many horticultural crops world over. RNAi technique has been found
quite successful in inducing virus resistance in horticultural crops in addition
to coat protein genes. Abiotic stresses such as drought, heat and salinity
adversely affect production and productivity of horticultural crops and a number
of genes encoding for biosynthesis of stress protecting compounds including
mannitol, glycine betaine and heat shock proteins have been employed for abiotic
stress tolerance besides various transcription factors like DREB1, MAPK, WRKY,
etc. Antisense gene and RNAi technologies have revolutionized the pace of
improvement of horticultural crops, particularly ornamentals for color
modification, increasing shelf-life and reducing post-harvest losses. Precise
genome editing tools, particularly CRISPR/Cas9, have been efficiently applied in
tomato, petunia, citrus, grape, potato and apple for gene mutation, repression,
activation and epigenome editing. This review provides comprehensive overview to
draw the attention of researchers for better understanding of genetic engineering
advancements in imparting biotic and abiotic stress tolerance as well as on
improving various traits related to quality, texture, plant architecture
modification, increasing shelf-life, etc. in different horticultural crops.
PMID- 28702939
TI - Genetic diversity and relatedness among ornamental purslane (Portulaca L.)
accessions unraveled by SRAP markers.
AB - Ornamental purslanes (Portulaca L.) are a popular annual bedding and container
plant for landscaping. Little information is available concerning the genetic
characterization of ornamental purslane resources thus far. The purpose of this
study was to investigate the genetic diversity and relationships present in a
collection of ornamental purslanes from Portulaca umbraticola and P. grandiflora
cultivated in China, using sequence-related amplified polymorphism (SRAP)
markers. The genotyping showed that 16 SRAP primer combinations totally produced
261 informative fragments and averaged 16.31 per primer combination. The major
allele frequency and Nei's gene diversity was calculated at 0.78 and 0.31 across
the loci, indicative of a moderate low diversity. Both unweighted pair group
method with arithmetic average (UPGMA) clustering and a Bayesian-based approach
apparently assigned the whole accessions into two sub-groups: P. umbraticola and
P. grandiflora, well concordant with the botanical classification and flower
type. The findings provide a brandnew understanding of genetic diversity and
population structure present in ornamental purslane, and benefit a sound design
of breeding programs in future.
PMID- 28702940
TI - Heart rate variability in critical care medicine: a systematic review.
AB - BACKGROUND: Heart rate variability (HRV) has been used to assess cardiac
autonomic activity in critically ill patients, driven by translational and
biomarker research agendas. Several clinical and technical factors can interfere
with the measurement and/or interpretation of HRV. We systematically evaluated
how HRV parameters are acquired/processed in critical care medicine. METHODS:
PubMed, MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials
(1996-2016) were searched for cohort or case-control clinical studies of adult
(>18 years) critically ill patients using heart variability analysis. Duplicate
independent review and data abstraction. Study quality was assessed using two
independent approaches: Newcastle-Ottowa scale and Downs and Black instrument.
Conduct of studies was assessed in three categories: (1) study design and
objectives, (2) procedures for measurement, processing and reporting of HRV, and
(3) reporting of relevant confounding factors. RESULTS: Our search identified
31/271 eligible studies that enrolled 2090 critically ill patients. A minority of
studies (15; 48%) reported both frequency and time domain HRV data, with non
normally distributed, wide ranges of values that were indistinguishable from
other (non-critically ill) disease states. Significant heterogeneity in HRV
measurement protocols was observed between studies; lack of adjustment for
various confounders known to affect cardiac autonomic regulation was common.
Comparator groups were often omitted (n = 12; 39%). This precluded meaningful
meta-analysis. CONCLUSIONS: Marked differences in methodology prevent meaningful
comparisons of HRV parameters between studies. A standardised set of consensus
criteria relevant to critical care medicine are required to exploit advances in
translational autonomic physiology.
PMID- 28702941
TI - An application of partial least squares for identifying dietary patterns in bone
health.
AB - : In a large cohort of older women, a mechanism-driven statistical technique for
assessing dietary patterns that considers a potential nutrient pathway found two
dietary patterns associated with lumbar spine and femoral neck bone mineral
density. A "healthy" dietary pattern was observed to be beneficial for bone
mineral density. INTRODUCTION: Dietary patterns represent a broader, more
realistic representation of how foods are consumed, compared to individual food
or nutrient analyses. Partial least-squares (PLS) is a data-reduction technique
for identifying dietary patterns that maximizes correlation between foods and
nutrients hypothesized to be on the path to disease, is more hypothesis-driven
than previous methods, and has not been applied to the study of dietary patterns
in relation to bone health. METHODS: Women from the Aberdeen Prospective
Osteoporosis Screening Study (2007-2011, n = 2129, age = 66 years (2.2)) provided
dietary intake using a food frequency questionnaire; 37 food groups were created.
We applied PLS to the 37 food groups and 9 chosen response variables (calcium,
potassium, vitamin C, vitamin D, protein, alcohol, magnesium, phosphorus, zinc)
to identify dietary patterns associated with bone mineral density (BMD) cross
sectionally. Multivariable regression was used to assess the relationship between
the retained dietary patterns and BMD at the lumbar spine and femoral neck,
adjusting for age, body mass index, physical activity level, smoking, and
national deprivation category. RESULTS: Five dietary patterns were identified,
explaining 25% of the variation in food groups and 77% in the response variables.
Two dietary patterns were positively associated with lumbar spine (per unit
increase in factor 2: 0.012 g/cm2 [95% CI: 0.006, 0.01]; factor 4: 0.007 g/cm2
[95% CI: 0.00001, 0.01]) and femoral neck (factor 2: 0.006 g/cm2 [95% CI: 0.002,
0.01]; factor 4: 0.008 g/cm2 [95% CI: 0.003, 0.01)]) BMD. Dietary pattern 2 was
characterized by high intakes of milk, vegetables, fruit and vegetable juices,
and wine, and low intakes of processed meats, cheese, biscuits, cakes, puddings,
confectionary, sweetened fizzy drinks and spirits while dietary pattern 4 was
characterized by high intakes of fruits, red and white meats, and wine, and low
intakes of vegetables and sweet spreads. CONCLUSION: Our findings using a robust
statistical technique provided important support to initiatives focusing on what
constitutes a healthy diet and its implications.
PMID- 28702942
TI - Baccalaureate-educated Registered Nurses in nursing homes: Experiences and
opinions of administrators and nursing staff.
AB - AIMS: To understand how nursing homes employ baccalaureate-educated Registered
Nurses (BRNs) and how they view the unique contributions of baccalaureate
educated Registered Nurses to staff and residents in their organizations.
BACKGROUND: Although providing care for nursing home residents is complex and
thus requires a high level of skills, organizations often struggle to recruit and
retain BRNs. Some nursing home organizations do not employ baccalaureate-educated
Registered Nurses at all. Among those that do, it is unknown how well these
organizations make use of baccalaureate-educated Registered Nurses' expertise or
if their roles are different from those of other staff. DESIGN: A qualitative
study, consisting of 26 individual and three group interviews was conducted in
the Netherlands. METHODS: Interviews were conducted at the board-, management-
and staff-level in six nursing home organizations. Data were collected between
January 2016-May 2016. RESULTS: Organizations employed baccalaureate-educated
Registered Nurses to fulfil an informal leadership role for direct care teams.
Organizations that do not employ baccalaureate-educated Registered Nurses were
unable to articulate their role in the nursing home setting. Difficulties
baccalaureate-educated Registered Nurses experienced during role implementation
depended on role clarity, the term used to refer to the baccalaureate-educated
Registered Nurse, the extent to which nurses received support, openness from
direct care teams and baccalaureate-educated Registered Nurses' own behaviour.
The unique contribution of baccalaureate-educated Registered Nurses perceived by
respondents differed between and in organizations. CONCLUSION: Our findings
suggest that there is no "one size fits all" approach to employing baccalaureate
educated Registered Nurses in nursing homes. To ensure the satisfaction of both
baccalaureate-educated Registered Nurses and the organizations that employ them,
careful implementation and evaluation of their role is crucial.
PMID- 28702943
TI - Screening and identification of metabolites of two kinds of main active
ingredients and hepatotoxic pyrrolizidine alkaloids in rat after lavage Farfarae
Flos extract by UHPLC-Q-TOF-MS mass spectrometry.
AB - Farfarae Flos, the dried flower buds of Tussilago farfara L., is usually used to
treat coughs, bronchitic and asthmatic conditions as an important traditional
Chinese medicine. Tussilagone and methl butyric acid tussilagin ester are seen as
representatives of two kinds of active substances. In addition, the pyrrolizidine
alkaloids, mainly senkirkine and senecionine, present in the herb can be
hepatoxic. In this study, a rapid and sensitive ultra-high-performance liquid
chromatography coupled with hybrid triple quadrupole time-of-flight mass
spectrometry method was successfully applied to identify the metabolites of
tussilagone, methl butyric acid tussilagin ester, senkirkine and senecionine. A
total of 35, 37, 18 and nine metabolites of tussilagone, methl butyric acid
tussilagin ester, senkirkine and senecionine in rats were tentatively identified.
Hydrolysis, oxidation, reduction and demethylation were the major metabolic
reactions for tussilagone and methl butyric acid tussilagin ester. The main
biotransformation routes of senkirkine and senecionine were identified as
demethylation, N-methylation, oxidation and reduction. This study is the first
reported analysis and characterization of the metabolites and the proposed
metabolic pathways might provide further understanding of the metabolic fate of
the chemical constituents after oral administration of Farfarae Flos extract in
vivo.
PMID- 28702944
TI - Impact of pre-operative health-related quality of life on outcomes after heart
surgery.
AB - BACKGROUND: Long-term improvement in health-related quality of life (HRQOL) is
one of the most important outcomes of cardiac surgery. The aim of this study is
to define the impact of perioperative patient and procedural variables on HRQOL
dynamics, a year after cardiac surgery. METHODS: Consecutive patients undergoing
elective on-pump cardiac surgery were enrolled in this prospective observational
cohort study. Patients completed the Medical Outcomes Study 36-Item Short-Form
Health Survey (SF-36) questionnaire a day before surgery and once again a year
after surgery. The effect size method was used to determine whether treatment
resulted in the improvement of HRQOL. RESULTS: A total of 67.3% of patients
achieved long-term improvement in HRQOL. Significant negative association was
identified between Physical and Mental Component Summary scores (PCS/MCS) and
long-term outcomes. Pre-operative PCS were 40.7 +/- 13.7 for improvers and 56.6
+/- 14.4 for non-improvers; MCS were 45.8 +/- 12.1 and 65.2 +/- 13.7,
respectively (P < 0.001 for all). There were no statistically significant
differences in pre-operative risk factors, demographics, operative factors or
post-operative variables between the two groups. CONCLUSION: Among those
completing this study, one in three patients did not experience long-term HRQOL
improvements following cardiac surgery. Multivariate analysis confirmed that
higher pre-operative PCS and MCS are independent predictors of worse HRQOL a year
after surgery. Further research should focus on establishing the prevalence of
this phenomenon worldwide and develop targeted interventions to improve long-term
self-perceived quality of life for patients with relatively good pre-operative
health.
PMID- 28702945
TI - Recognizing European cancer nursing: Protocol for a systematic review and meta
analysis of the evidence of effectiveness and value of cancer nursing.
AB - AIM: To identify, appraise and synthesize the available evidence relating to the
value and impact of cancer nursing on patient experience and outcomes.
BACKGROUND: There is a growing body of literature that recognizes the importance
and contribution of cancer nurses, however, a comprehensive review examining how
cancer nurses have an impact on care quality, patient outcomes and overall
experience of cancer, as well as cost of services across the entire cancer
spectrum is lacking. DESIGN: A systematic review and meta-analysis using Cochrane
methods. METHODS: We will systematically search 10 electronic databases from
2000, with pre-determined search terms. No language restrictions will be applied.
We will include all randomized and controlled before-and-after studies that
compare cancer nursing interventions to a standard care or no intervention. Two
reviewers will independently assess the eligibility of the studies and appraise
methodological quality using the Cochrane Risk of Bias tool. Disagreements will
be resolved by discussion and may involve a third reviewer if necessary. Data
from included studies will be extracted in accordance with the Template for
intervention Description and Replication reporting guidelines. Missing data will
be actively sought from all trialists. Data will be synthesized in evidence
tables and narrative to answer three key questions. If sufficient data are
available, we will perform meta-analyses. DISCUSSION: This review will allow us
to systematically assess the impact of cancer nursing on patient care and
experience. This evidence will be used to determine implications for clinical
practice and used to inform future programme and policy decisions in Europe.
PMID- 28702946
TI - Massive choroidal granuloma as the presenting feature of disseminated
tuberculosis in immunocompetent patients.
PMID- 28702947
TI - Initial validation of a healthcare needs scale for young people with congenital
heart disease.
AB - AIM: To validate the initial psychometric properties of a Healthcare Needs Scale
for Youth with Congenital Heart Disease. BACKGROUND: As the number of patients
with congenital heart disease surviving to adulthood increases, the transitional
healthcare needs for adolescents and young adults with congenital heart disease
require investigation. However, few tools comprehensively identify the healthcare
needs of youth with congenital heart disease. DESIGN: A cross-sectional study was
employed to examine the psychometric properties of the Healthcare Needs Scale for
Youth with Congenital Heart Disease. METHODS: The sample consisted of 500
patients with congenital heart disease, aged 15-24 years, from paediatric
cardiology departments and covered the period from March-August 2015. The
patients completed the 25-item Healthcare Needs Scale for Youth with Congenital
Heart Disease, the questionnaire on health needs for adolescents and the WHO
Quality of Life-BREF. Reliability and construct, concurrent, predictive and known
group validity were examined. RESULTS: The Healthcare Needs Scale for Youth with
Congenital Heart Disease includes three dimensions, namely health management,
health policy and individual and interpersonal relationships, which consist of 25
items. It demonstrated excellent internal consistency and sound construct,
concurrent, predictive and known-group validity. CONCLUSION: The Healthcare Needs
Scale for Youth with Congenital Heart Disease is a psychometrically robust
measure of the healthcare needs of youth with congenital heart disease. It has
the potential to provide nurses with a means to assess and identify the concerns
of youth with congenital heart disease and to help them achieve a successful
transition to adult care.
PMID- 28702948
TI - Pathological prognostic factors of recurrence in early stage lung adenocarcinoma.
AB - BACKGROUND: Histological heterogeneity is thought to be important for prognosis
of lung adenocarcinoma. We investigated to determine pathological features with
prognostic value for recurrence of early stage lung cancer. METHODS: A total of
368 patients who underwent curative surgical resection for early stage lung
adenocarcinoma between 2009 and 2012 were enrolled. Pathologic characteristics
including the presence of visceral pleural invasion, micropapillary patterns,
aerogenous spread, lymphovascular invasion, perineural invasion and necrosis were
examined. The correlations between pathological factors and clinical outcomes
were analysed to determine prognostic significance. RESULTS: Mean follow-up was
43.0 months (+/-14.56, ranging from 0.0 to 73.9 months). Three-year overall
survival was 95.2% and disease-free survival was 89.8%. The recurrence rate was
9.0% (33 patients) and the mortality rate was 6.0% (22 patients). The presence of
a micropapillary pattern (P < 0.002), lymphatic invasion (P < 0.000), aerogenous
spread (P < 0.000), vascular invasion (P = 0.036) and necrosis (P < 0.000) were
negative prognostic factors of recurrence in univariate analysis. In multivariate
analysis, only aerogenous spread had prognostic value (P = 0.020). The recurrence
hazard ratio for the presence of aerogenous spread was 3.2 (95% confidence
interval 1.20-8.47). CONCLUSION: The presence of aerogenous spread was an
independent pathological risk factor of recurrence in stage I lung
adenocarcinoma. Micropapillary pattern had prognostic importance for recurrence
in univariate analysis, but not in multivariate analysis.
PMID- 28702949
TI - Genetic analysis of optic nerve head coloboma in the Nova Scotia Duck Tolling
Retriever identifies discordance with the NHEJ1 intronic deletion (collie eye
anomaly mutation).
AB - Collie eye anomaly (CEA) encompasses a spectrum of different ophthalmic
phenotypes from clinically inconsequential choroidal hypoplasia to blindness from
coloboma of the optic nerve head (ONH). A previous study found a 7.8-kb deletion
in intron 4 of the NHEJ1 gene to be associated with CEA. A genetic test based on
this association is recommended for many breeds, including the Nova Scotia Duck
Tolling Retriever (NSDTR). Collection of ONH coloboma-affected NSDTR showed lack
of concordance of the NHEJ1 intronic deletion with ONH coloboma. Using genomewide
single nucleotide polymorphism (SNP) genotyping in 7 ONH coloboma-affected NSDTR
cases and 47 unaffected NSDTR controls with no ophthalmic signs, one SNP, located
on chromosome 7, demonstrated genomewide significance. However, high genomic
inflation may have confounded the results. Therefore, the genomewide association
study was repeated using EMMAX to control for population structure in the cohort
of 7 cases and 47 controls. However, no regions of the genome were significantly
associated with ONH coloboma. These results failed to document significant
association with the CEA locus. Due to the complex genetic etiology of ONH
coloboma, the NHEJ1 intronic deletion test results should be carefully considered
when making breeding decisions. If the goal is to select for visually competent
dogs, our data suggest that eye examinations of puppies would be more effective
as a guide in selection of breeding pairs than relying solely on currently
available genetic tests.
PMID- 28702950
TI - Gender, ethnicity and smoking affect pain and function in patients with rotator
cuff tears.
AB - BACKGROUND: This study is a collation of baseline demographic characteristics of
those presenting for rotator cuff repair in New Zealand, and exploration of
associations with preoperative function and pain. Data were obtained from the New
Zealand Rotator Cuff Registry; a multicentre, nationwide prospective cohort of
rotator cuff repairs undertaken from 1 March 2009 until 31 December 2010.
METHODS: A total of 1383 patients were included in the study. This required
complete demographic information, preoperative Flex-SF (functional score) and
pain scores. Following univariate analysis, a multivariate model was used.
RESULTS: The average age was 58 years (69% males and 11% smokers). New Zealand
Europeans made up 90% and Maori 5%. The average preoperative Flex-SF was
significantly lower (poorer function) in those over 65 years, females, smokers
and Maori, in the non-dominant patients, using a multivariate model. Average
preoperative pain scores were significantly worse (higher scores) in females,
Maori, Polynesians, smokers, using a multivariate model. CONCLUSION: This is the
largest reported prospective cohort of patients presenting for rotator cuff
surgery. Results can be used to understand the effect of rotator cuff tears on
the different patients, for example Maori patients who are under-represented,
present younger, with more pain and poorer function.
PMID- 28702951
TI - The prevalence of refractive errors among adult rural populations in Iran.
AB - PURPOSE: The aim was to determine the prevalence of myopia and hyperopia and
related factors in underserved rural areas in Iran. METHODS: Under random cluster
sampling, two rural regions were randomly selected in the north and southwest of
the country, and 3,061 persons over 15 years of age were invited into the study.
After selecting samples, all participants had refraction, measurement of
uncorrected vision and visual acuity and ocular health examination by slitlamp
biomicroscopy. RESULTS: Of the 3,061 invitees, 2,575 participated in the study
(response rate: 84.1 per cent). After excluding those who met the exclusion
criteria or had missing refractive data, eventually there were 2,518 subjects
available for this analysis. The mean age of the participants was 44.3 +/- 17.5
years (range: 16 to 93 years) and 1,460 of them (58.0 per cent) were female. The
overall prevalence of myopia and hyperopia in this study was 25.2 per cent (95
per cent CI: 23.2 to 27.2) and 22.5 per cent (95 per cent CI: 20.6 to 24.4),
respectively. The prevalence of myopia increased from 20.9 per cent in
participants 16 to 20 years to 32.9 per cent in the 21 to 30 years age group,
declined up to the age of 60 years and increased again afterwards. The lowest
prevalence was 6.8 per cent observed in the 16 to 20 years age group and the
highest was 45.8 per cent in 61- to 70-year-olds. In the final logistic
regression model, myopia significantly associated with age, higher education
levels and cataracts, while hyperopia associated with age, lower education levels
and male gender. CONCLUSION: In our study, the prevalence of myopia was lower and
the prevalence of hyperopia was higher compared to most previous studies. The
findings of this study imply that refractive errors vary by age.
PMID- 28702952
TI - The nurse-patient relationship as a story of health enhancement in community
care: A meta-ethnography.
AB - AIM: To explore and improve our understanding of how nurse-patient relationships
can enhance patients' health by synthesizing knowledge from published qualitative
studies from both patients' and nurses' perspectives in community care.
BACKGROUND: While primary research showing the health benefits of the nurse
patient relationship has been reported, this knowledge has not previously been
synthesized. DESIGN: Meta-ethnography. DATA SOURCES: A comprehensive search of
five relevant databases, without year limitation, was completed. Inclusion
criteria were: peer-reviewed studies exploring patient and/or nurse perspectives
in community care settings, using a qualitative approach and published in English
in any country. REVIEW METHOD: Noblit and Hare's meta-ethnographic approach.
RESULTS: Ten primary studies published between 1997 - 2014 met the research
objective and inclusion criteria and were appraised as high quality using CASP.
Included studies reported similar findings and reciprocal translational analysis
was possible. Six core themes were identified: entering the patient's world;
trusting and telling; identifying different needs and uncovering change; patients
becoming masters of their own health; patients experiencing health in illness;
and nurses going the distance. The core themes were synthesized into a metaphor
of "the nurse-patient relationship as a story of health enhancement", which
illustrates the meaning of the "common story" they create together. CONCLUSION:
The findings help us better understand how the nurse-patient relationship may
enhance the patient's health, not only with regard to illness, physical condition
and treatment but also physical, emotional, mental and social well-being. The
nurse-patient relationship also has the potential to strengthen the patient's own
resources towards maintaining health.
PMID- 28702953
TI - Characteristics and survey of keratoconic contact lens wearers who are lost to
follow up.
PMID- 28702954
TI - Geometrical study of phyllotactic patterns by Bernoulli spiral lattices.
AB - Geometrical studies of phyllotactic patterns deal with the centric or cylindrical
models produced by ideal lattices. van Iterson (Mathematische und mikroskopisch -
anatomische Studien uber Blattstellungen nebst Betrachtungen uber den Schalenbau
der Miliolinen, Verlag von Gustav Fischer, Jena, 1907) suggested a centric model
representing ideal phyllotactic patterns as disk packings of Bernoulli spiral
lattices and presented a phase diagram now called Van Iterson's diagram
explaining the bifurcation processes of their combinatorial structures.
Geometrical properties on disk packings were shown by Rothen & Koch (J. Phys
France, 50(13), 1603-1621, 1989). In contrast, as another centric model, we
organized a mathematical framework of Voronoi tilings of Bernoulli spiral
lattices and showed mathematically that the phase diagram of a Voronoi tiling is
graph-theoretically dual to Van Iterson's diagram. This paper gives a review of
two centric models for disk packings and Voronoi tilings of Bernoulli spiral
lattices.
PMID- 28702955
TI - Mentors' competence in mentoring culturally and linguistically diverse nursing
students during clinical placement.
AB - AIMS: To describe mentors' competence in mentoring culturally and linguistically
diverse nursing students during clinical placement and identify the factors that
affect mentoring. BACKGROUND: Healthcare education is confronted by several
challenges in a time characterized by globalization and increasing international
migration. Nursing students from diverse backgrounds continue to experience
difficulties during clinical placement. Students can overcome these difficulties
and assume responsibility for their learning when mentored by supportive and
competent mentors. DESIGN: A cross-sectional, descriptive explorative study
design was used. METHODS: Data were collected during spring 2016 through a survey
sent to mentors (n = 3,355) employed at five university hospitals in Finland.
Mentors' competence in mentoring culturally and linguistically diverse nursing
students was measured with the self-assessment Mentors' Competence Instrument and
the Cultural and Linguistic Diversity in Mentoring scale. The analysis included
descriptive statistics, non-parametric tests and binary logistic regression
analysis. RESULTS: Mentors with experience mentoring nursing students from
diverse backgrounds rated their overall competence in mentoring as good. However,
the results show continued challenges related to competence in linguistic
diversity in mentoring. Seven factors that affect mentors' competence in
linguistic diversity were identified. Despite high evaluations by mentors of
competence related to cultural diversity in mentoring, there are still
opportunities for improvement in this area. CONCLUSION: Innovative and effective
strategies are needed to develop mentors' competence in mentoring culturally and
linguistically diverse nursing students. Educational and healthcare organizations
should strive to enhance collaboration and increase the competence of both
mentors and nursing students to work in increasingly diverse healthcare
environments.
PMID- 28702956
TI - Interventions for treating lymphocytic colitis.
AB - BACKGROUND: Lymphocytic colitis is a cause of chronic diarrhea. It is a subtype
of microscopic colitis characterized by chronic, watery, non-bloody diarrhea and
normal endoscopic and radiologic findings. The etiology of this disorder is
unknown.Therapy is based mainly on case series and uncontrolled trials, or by
extrapolation of data for treating collagenous colitis, a related disorder. This
review is an update of a previously published Cochrane review. OBJECTIVES: To
evaluate the efficacy and safety of treatments for clinically active lymphocytic
colitis. SEARCH METHODS: The MEDLINE, PUBMED and EMBASE databases were searched
from inception to 11 August 2016 to identify relevant papers. Manual searches
from the references of included studies and relevant review articles were
performed.Abstracts from major gastroenterological meetings were also searched to
identify research submitted in abstract form only. The trial registry web site
www.ClinicalTrials.gov was searched to identify registered but unpublished
trials. Finally, the Cochrane Central Register of Controlled Trials and the
Cochrane Inflammatory Bowel Disease and Functional Bowel Disorders Group
Specialized Trials Register were searched for other studies. SELECTION CRITERIA:
Randomized controlled trials assessing medical therapy for patients with biopsy
proven lymphocytic colitis were considered for inclusion DATA COLLECTION AND
ANALYSIS: Data was independently extracted by at least two authors. Any
disagreements were resolved by consensus. Data were analyzed on an intention-to
treat (ITT) basis. The primary outcome was clinical response as defined by the
included studies. Secondary outcome measures included histological response as
defined by the included studies, quality of life as measured by a validated
instrument and the occurrence of adverse events. Risk ratios (RR) and 95%
confidence intervals (CI) were calculated for dichotomous outcomes. The
methodological quality of included studies was evaluated using the Cochrane risk
of bias tool. The overall quality of the evidence supporting the primary outcome
and selected secondary outcomes was assessed using the GRADE criteria. Data were
combined for analysis if they assessed the same treatments. Dichotomous data were
combined using a pooled RR along with corresponding 95% CI. A fixed-effect model
was used for the pooled analysis. MAIN RESULTS: Five RCTs (149 participants) met
the inclusion criteria. These studies assessed bismuth subsalicylate versus
placebo, budesonide versus placebo, mesalazine versus mesalazine plus
cholestyramine and beclometasone dipropionate versus mesalazine. The study which
assessed mesalazine versus mesalazine plus cholestyramine and the study which
assessed beclometasone dipropionate versus mesalazine were judged to be at high
risk of bias due to lack of blinding. The study which compared bismuth
subsalicylate versus us placebo was judged as low quality due to a very small
sample size and limited data. The other 3 studies were judged to be at low risk
of bias. Budesonide (9 mg/day for 6 to 8 weeks) was significantly more effective
than placebo for induction of clinical and histological response. Clinical
response was noted in 88% of budesonide patients compared to 38% of placebo
patients (2 studies; 57 participants; RR 2.03, 95% CI 1.25 to 3.33; GRADE = low).
Histological response was noted in 78% of budesonide patients compared to 33% of
placebo patients (2 studies; 39 patients; RR 2.44, 95% CI 1.13 to 5.28; GRADE =
low). Forty-one patients were enrolled in the study assessing mesalazine (2.4
g/day) versus mesalazine plus cholestyramine (4 g/day). Clinical response was
noted in 85% of patients in the mesalazine group compared to 86% of patients in
the mesalazine plus cholestyramine group (RR 0.99, 95% CI 0.77 to 1.28; GRADE =
low). Five patients were enrolled in the trial studying bismuth subsalicylate
(nine 262 mg tablets daily for 8 weeks versus placebo). There were no differences
in clinical (P=0.10) or histological responses (P=0.71) in patients treated with
bismuth subsalicylate compared with placebo (GRADE = very low). Forty-six
patients were enrolled in the trial studying beclometasone dipropionate (5 mg/day
or 10 mg/day) versus mesalazine (2.4 g/day). There were no differences in
clinical remission at 8 weeks (RR 0.97; 95% CI 0.75 to 1.24; GRADE = low) and 12
months of treatment (RR 1.29; 95% CI 0.40 to 4.18; GRADE = very low). Although
patients receiving beclometasone dipropionate (84%) and mesalazine (86%) achieved
clinical remission at 8 weeks, it was not maintained at 12 months (26% and 20%,
respectively). Adverse events reported in the budesonide studies include nausea,
vomiting, neck pain, abdominal pain, hyperhidrosis and headache. Nausea and skin
rash were reported as adverse events in the mesalazine study. Adverse events in
the beclometasone dipropionate trial include nausea, sleepiness and change of
mood. No adverse events were reported in the bismuth subsalicylate study.
AUTHORS' CONCLUSIONS: Low quality evidence suggests that budesonide may be
effective for the treatment of active lymphocytic colitis. This benefit needs to
be confirmed by a large placebo -controlled trial. Low quality evidence also
suggests that mesalazine with or without cholestyramine and beclometasone
dipropionate may be effective for the treatment of lymphocytic colitis, however
this needs to be confirmed by large placebo-controlled studies. No conclusions
can be made regarding bismuth subsalicylate due to the very small number of
patients in the study, Further trials studying interventions for lymphocytic
colitis are warranted.
PMID- 28702957
TI - Non-invasive ventilation for the management of acute hypercapnic respiratory
failure due to exacerbation of chronic obstructive pulmonary disease.
AB - BACKGROUND: Non-invasive ventilation (NIV) with bi-level positive airway pressure
(BiPAP) is commonly used to treat patients admitted to hospital with acute
hypercapnic respiratory failure (AHRF) secondary to an acute exacerbation of
chronic obstructive pulmonary disease (AECOPD). OBJECTIVES: To compare the
efficacy of NIV applied in conjunction with usual care versus usual care
involving no mechanical ventilation alone in adults with AHRF due to AECOPD. The
aim of this review is to update the evidence base with the goals of supporting
clinical practice and providing recommendations for future evaluation and
research. SEARCH METHODS: We identified trials from the Cochrane Airways Group
Specialised Register of trials (CAGR), which is derived from systematic searches
of bibliographic databases including the Cochrane Central Register of Controlled
Trials (CENTRAL), MEDLINE, Embase, the Cumulative Index to Nursing and Allied
Health Literature (CINAHL), the Allied and Complementary Medicine Database
(AMED), and PsycINFO, and through handsearching of respiratory journals and
meeting abstracts. This update to the original review incorporates the results of
database searches up to January 2017. SELECTION CRITERIA: All randomised
controlled trials that compared usual care plus NIV (BiPAP) versus usual care
alone in an acute hospital setting for patients with AECOPD due to AHRF were
eligible for inclusion. AHRF was defined by a mean admission pH < 7.35 and mean
partial pressure of carbon dioxide (PaCO2) > 45 mmHg (6 kPa). Primary review
outcomes were mortality during hospital admission and need for endotracheal
intubation. Secondary outcomes included hospital length of stay, treatment
intolerance, complications, changes in symptoms, and changes in arterial blood
gases. DATA COLLECTION AND ANALYSIS: Two review authors independently applied the
selection criteria to determine study eligibility, performed data extraction, and
determined risk of bias in accordance with Cochrane guidelines. Review authors
undertook meta-analysis for data that were both clinically and statistically
homogenous, and analysed data as both one overall pooled sample and according to
two predefined subgroups related to exacerbation severity (admission pH between
7.35 and 7.30 vs below 7.30) and NIV treatment setting (intensive care unit-based
vs ward-based). We reported results for mortality, need for endotracheal
intubation, and hospital length of stay in a 'Summary of findings' table and
rated their quality in accordance with GRADE criteria. MAIN RESULTS: We included
in the review 17 randomised controlled trials involving 1264 participants.
Available data indicate that mean age at recruitment was 66.8 years (range 57.7
to 70.5 years) and that most participants (65%) were male. Most studies (12/17)
were at risk of performance bias, and for most (14/17), the risk of detection
bias was uncertain. These risks may have affected subjective patient-reported
outcome measures (e.g. dyspnoea) and secondary review outcomes, respectively.Use
of NIV decreased the risk of mortality by 46% (risk ratio (RR) 0.54, 95%
confidence interval (CI) 0.38 to 0.76; N = 12 studies; number needed to treat for
an additional beneficial outcome (NNTB) 12, 95% CI 9 to 23) and decreased the
risk of needing endotracheal intubation by 65% (RR 0.36, 95% CI 0.28 to 0.46; N =
17 studies; NNTB 5, 95% CI 5 to 6). We graded both outcomes as 'moderate' quality
owing to uncertainty regarding risk of bias for several studies. Inspection of
the funnel plot related to need for endotracheal intubation raised the
possibility of some publication bias pertaining to this outcome. NIV use was also
associated with reduced length of hospital stay (mean difference (MD) -3.39 days,
95% CI -5.93 to -0.85; N = 10 studies), reduced incidence of complications
(unrelated to NIV) (RR 0.26, 95% CI 0.13 to 0.53; N = 2 studies), and improvement
in pH (MD 0.05, 95% CI 0.02 to 0.07; N = 8 studies) and in partial pressure of
oxygen (PaO2) (MD 7.47 mmHg, 95% CI 0.78 to 14.16 mmHg; N = 8 studies) at one
hour. A trend towards improvement in PaCO2 was observed, but this finding was not
statistically significant (MD -4.62 mmHg, 95% CI -11.05 to 1.80 mmHg; N = 8
studies). Post hoc analysis revealed that this lack of benefit was due to the
fact that data from two studies at high risk of bias showed baseline imbalance
for this outcome (worse in the NIV group than in the usual care group).
Sensitivity analysis revealed that exclusion of these two studies resulted in a
statistically significant positive effect of NIV on PaCO2. Treatment intolerance
was significantly greater in the NIV group than in the usual care group (risk
difference (RD) 0.11, 95% CI 0.04 to 0.17; N = 6 studies). Results of analysis
showed a non-significant trend towards reduction in dyspnoea with NIV compared
with usual care (standardised mean difference (SMD) -0.16, 95% CI -0.34 to 0.02;
N = 4 studies). Subgroup analyses revealed no significant between-group
differences. AUTHORS' CONCLUSIONS: Data from good quality randomised controlled
trials show that NIV is beneficial as a first-line intervention in conjunction
with usual care for reducing the likelihood of mortality and endotracheal
intubation in patients admitted with acute hypercapnic respiratory failure
secondary to an acute exacerbation of chronic obstructive pulmonary disease
(COPD). The magnitude of benefit for these outcomes appears similar for patients
with acidosis of a mild (pH 7.30 to 7.35) versus a more severe nature (pH <
7.30), and when NIV is applied within the intensive care unit (ICU) or ward
setting.
PMID- 28702958
TI - Extracorporeal CO2 removal: a powerful tool to be handled with care.
PMID- 28702959
TI - Treatment of skin defects with growth factors and biodegradable collagen carrier:
histological evaluation in animal model.
AB - The aim of the present study is to evaluate the effects on skin regeneration of a
new collagen matrix (CM-10826) when used in different combination with or without
growth factors, using skin regeneration without membrane as control. An area of
10x15 cm on rabbit back was shaved and three circular wounds on test side were
covered with a differently soaked membrane. The first wound was soaked with
Epidermal Growth Factor (EGF, 26mg/130mL) (Test EGF), the second with Platelet
Derived Growth Factor (PDGF, 6mg/120mL) (Test PDGF) and the third with EGF
(13mg/65mL) and PDGF (3mg/60mL) (Test EGF+PDGF). On the control side, there was a
dry membrane. After 7 days, the experiment was concluded. Healing process was
evaluated at day 2 and 6 postoperatively. Analysis was made clinically and with
light microscopy (LM), transmission electron microscopy (TEM) and scanning
electron microscopy (SEM). Analyses with LM of Test EGF showed evidence of
neoangiogenesis and good epithelium growth. Test PDGF resulted in moderate
angiogenesis, less evident epithelial growth and more evident mesenchymal growth
than Test EGF. Test EGF+PDGF showed rich angiogenesis, massive growth of
epithelium and mesenchymal tissue. Control side showed weak angiogenesis,
regenerating wound margin with normal epithelium and less dense mesenchymal
layer. Analysis at TEM and SEM confirmed what was noticed at LM. In vivo studies
on rabbits have shown that membrane CM10826 is well tolerated, it gives neither
inflammation nor foreign body reactions and does not disturb healing process.
CM10826 is safe, modulates angiogenesis and induces migration and proliferation
of keratinocytes.
PMID- 28702960
TI - Buccal bone dimensions and aesthetic outcome at maxillary incisors replaced by
conventional dental implants. A case series with a 5-year follow-up.
AB - In the aesthetic field, successful replacement of a tooth with a dental implant
requires blend and harmony within the existing dentition. The influence of the
dimension of buccal bone at implant sites on aesthetic outcomes and the relation
between buccal bone horizontal and vertical dimensions are unclear. The aim of
the present study is to investigate the correlation between buccal bone
thickness, buccal bone level and aesthetic outcome in conventionally placed
implants - placed five or more years previously - supporting single maxillary
incisors. Eight subjects with 8 implants and with periapical and parallel profile
X-rays were clinically examined to assess the "Pink Aesthetic Score" (PES).
Buccal bone level and thickness, together with the interproximal bone level, were
measured. Implant survival was 100%. The mean time of implants function was 89.3
months (standard deviation 43, range 61-145). The mean PES value was 9.4. The
mean interproximal bone level was located 1.3 mm apically to the implant abutment
junction, while the corresponding buccal value was 1.6 mm. Buccal bone was mostly
absent at the implant abutment junction; 2 and 4 mm apically respect to the
junction the thickness was on average 0.44 and 0.89 mm, respectively. The
dimension of buccal bone level was correlated to the buccal bone thickness at 2mm
level, to the interproximal bone level and to the soft tissue contour score.
Conventional implant placement in pristine bone might lead to satisfactory long
term aesthetic results. The level of the facial mucosa and appearance of the
alveolar process might emerge as critical aspects.
PMID- 28702961
TI - Cutaneous manifestations in Steinert's disease. Apropos of four clinical cases.
AB - Myotonic dystrophy type 1 (MD1) (OMIM 160900, Steinert disease) is the most
common muscular disease, with an estimated worldwide prevalence ranging from 0.5
to 18/10,000 (1). MD1 is an autosomal dominant multisystem disorder that affects
skeletal and smooth muscles as well as eyes, heart, endocrine system, and central
nervous system. Available data on skin and adnexal involvement that has been
demonstrated as a hallmark of the neurological disease are still poor. The aim of
this case report-based, mini review on MD1 and skin is to highlight the
importance of such superficial signs to be easily detected in the physical
examination, and to evaluate the occurrence of these cutaneous manifestations in
presence of various degrees of the disease and gene mutations.
PMID- 28702962
TI - Unexpected parasitosis.
AB - Neotrombicula autumnalis is an arthropod living in the soil and parasitizes
animals only in its larval stage. Depending on climatic conditions, one to five
life cycles can take place in a single year. Human infestation is probably
underestimated and can be easily missed due to non-pathognomonic cutaneous
manifestations in absence of systemic signs. We describe a case of human
trombiculiasis and discuss the diagnostic and therapeutic management of this
'synanthropic' dermatosis.
PMID- 28702963
TI - Duncan's dermatosis: from the "terra firma-forme" to a possible syndromic
condition. The story of a dirty disease.
AB - Since its first description by Duncan, Tschen and Knox in 1987 in the former
Archives of Dermatology (1), "Terra firma-forme dermatosis" has been variously
described in medical literature, representing a strange, probably underestimated,
cutaneous disease. During the last 40 years, the condition has been recorded as
an undesirable as well as unexplained event, occurring mainly in childhood,
characterized by a brownish-black appearance of the whole skin, resembling dirt.
Recently, authors described several cases of atypical patterns of the disease,
sometimes with impressing topographic clinical pictures, evocative for syndromic
phenotypes. Thanks to more careful examination of the tegument, often with the
aid of non-invasive diagnostic tools, attention to this disease is growing. This
brief review summarizes the state of the art on the topic, through an historical
overview of what is known of this 'dirty' dermatosis.
PMID- 28702964
TI - Stigmata in the history: between faith, mysticism and science.
AB - Stigmata are one of the most ancient and fascinating mysteries of the Christian
religion. The word "stigmata" derives by the Greek "stigma", that means sign,
mark. Classically, stigmata are the sores inflicted on Jesus Christ during his
passion and crucifixion. Today, the term stigmatized has been extended to
designate several cases of individuals, who show skin sores similar to those of
Christ. The Authors report a brief history of stigmata, trying to give an
explanation to such a fascinating phenomenon.
PMID- 28702965
TI - Hard to face: cutaneous malignant melanoma.
AB - An 88-year-old Caucasian man recently sought medical attention due to
recrudescence of skin disease in the area of previously excised nodule (in 2002)
on the nose dorsum. The original lesion was clinically considered as a pigmented
basal cell carcinoma, after which histological examination revealed a superficial
spreading melanoma in vertical growth face (Clark level IV; Breslow thickness 2.1
mm) arising from a pre-existing nevus. The adjacent skin also showed significant
actinic damage both in the epidermis and in the dermis. A sentinel node was
positive (micrometastases of melanoma) and radical lymph node dissection of the
neck was performed. Other lymph nodes did not contain metastasis. Computed
tomography scans of brain, chest, abdomen and pelvis performed at that time
showed no evidence of systemic disease.
PMID- 28702966
TI - Possible role of Helicobacter pylori in diseases of dermatological interest.
AB - Helicobacter pylori is a gram-negative, flagellate, microaerophilic bacterium
identified for the first time about 30 years ago, as a pathogenic factor of
gastritis and peptic ulcer. Soon after, it was linked to several gastrointestinal
and extra-gastrointestinal diseases (hematological, cardiovascular, neurological,
pulmonary and ocular diseases, obesity, diabetes mellitus, growth retardation and
extragastric MALT lymphoma). Association and possible cause-effect correlation
with H. pylori infection were suggested in diseases of dermatological interest
such as chronic urticaria, rosacea, Henoch-Schoenleins purpura, idiopathic
thrombocytopenic purpura, cutaneous and oral lichen planus, atopic dermatitis,
recurrent aphthous stomatitis, systemic sclerosis, psoriasis, Sjogrens syndrome,
Behcet's disease, pruritus, alopecia areata, primary cutaneous marginal zone B
cell lymphomas, vitiligo, chronic prurigo, multiformis, prurigo nodularis,
leukocytoclastic vasculitis, prurigo pigmentosa, eczema nummulare, primary
cutaneous MALT-type lymphoma, sublamina densa-type linear IgA bullous dermatosis,
Sweet's syndrome, cutaneous T-cell pseudolymphoma and pemphigus vulgaris. A
critical review of the literature up to May 2017 shows clear evidence of H.
pylori involvement only for some of the above purported associations, while in
the majority of cases data appear contrasting and/or obtained on a not adequately
large study population. Further clinical and laboratory research, with more
adequate methodological and statistical basis, is required to assess the actual
existence and relevance of many purported associations, as well as the possible
role of H. pylori and the underlying pathogenic mechanisms.
PMID- 28702967
TI - Morphological evidences following pegylated filler treatment in human skin.
AB - In this study, microscopic, histochemical and ultrastructural observations in
human skin are presented, 8 months after an injection of a novel PEGylated
filler. Morphological features demonstrated an excellent integration of the
filler with the connective tissue components and an effective interpenetration
with the ground substance. The filler appears uniformly distributed inside the
hypodermis. No segregation or encapsulation of cells and other structures was
observed nor evidence of immunological adverse reaction. Furthermore, observed
ultrastructural modifications of fibroblasts supports a stimulatory effect of
molecular components production of the extracellular matrix, contributing to the
cutaneous connective tissue renewal.
PMID- 28702968
TI - In vitro evaluation of collagen production on human fibroblasts treated with
hyaluronic acid peg cross-linked with micromolecules of calcium hydroxyapatite in
low concentration.
AB - Neauvia Stimulate(r) is a biocompatible, injectable hyaluronic acid (HA) filler
(26 mg/ml) PEG cross-linked with 1% of calcium hydroxyapatite (CaHA) for facial
soft-tissue augmentation that provides volume to tissues, followed by a process
of neocollagenesis for improving skin quality. The aim of the present study is to
evaluate the possible modulation of collagen synthesis after treating human
fibroblasts cultured in vitro with the product (Lot. 160517-26-1/2 PEG). The
experimental model proposed, despite being an in vitro system, allows the
derivation of useful information to predict the possible activity of the product
in further in vivo application. Human fibroblasts (PEU cells) were treated with
the product for 24 h at increasing concentrations of compared to control
(untreated cells). The modulation of collagen synthesis was evaluated using a
specific colorimetric kit (Sircol, Soluble Collagen Assay Kit). Increment of
collagen production, 37.62% and 97.39% at concentrations of 1.25 mg/ml and 2.5
mg/ml of product, respectively, was considered to be statistically significant
(*p values<=0.05 and **p values<=0.01) when compared with control (untreated
cells). In conclusion, Hyaluronic Acid Hydrogel 26 mg/ml PEG cross-linked with
calcium hydroxyapatite in low concentrations (1%) determines a statistical
increment in neocollagenesis.
PMID- 28702969
TI - Bi-layered collagen nano-structured membrane prototype collagen matrix 10826(r)
for soft tissue regeneration in rabbits: an in vivo ultra-structural study of the
early healing phase.
AB - Collagen Matrix (CM) 10826 is a nanostructured bi-layered collagen membrane
obtained from type I and III porcine collagen, which in vitro has shown to have
the potential to be a substitute and/or stimulant for soft oral tissue
regeneration. The objective of this study was to evaluate the in vivo potential
and safety of this membrane for soft tissue regeneration in the early stage of
wound healing. Two soft tissue wounds (test and control) were created on the back
skin of 5 rabbits (female New Zealand White Rabbits specific pathogen free). All
wounds were protected by a special poly-tetra-fluoro-ethylene (PTFE) healing
camera. On each rabbit on the test side CM-10826 was used, while on the control
side conventional treatment (an autologous pedicle graft) was performed. The
healing process was observed clinically after 2 and 6 days, and Magnetic
Resonance Imaging (MRI) was performed after this period. After 7 days, animals
were sacrificed and specimens were analyzed with light optic microscopy (LM),
Transmission Electron Microscopy (TEM) and Scanning Electron Microscopy (SEM).
These in vivo trials on rabbits confirmed that CM-10826 is well tolerated,
without signs of histological inflammatory reaction and proved to be able to
accelerate the spontaneous repair of the skin defect taken as the control. The
light-optic and ultra-microscopy of serial biopsies showed that the new matrix is
biocompatible and is able to function as a scaffold inducing soft tissue
regeneration. In conclusion this study demonstrates that CM-10826 promote early
soft tissue regeneration and suggests it is a potential constituent for human
autologous keratinocytes seeded derma bioequivalent. It protects the wound from
injuries and bacterial contamination accelerating healing process. As a clinical
relevance, we consider that the quality of life of patients will be improved
avoiding the use of major autologous grafts, reducing the hospitalization time
and morbidity.
PMID- 28702970
TI - A novel CAD/CAM-based surgical template for mandibular osteoplasty and guided
implant insertion.
AB - Bone shaping is often a necessary procedure prior to implant insertion in
mandibular full-arch rehabilitations. Adopting guided surgery procedures is
necessary to use two distinct templates: one for bone shaping, a second for
guided implant insertion. The present report describes the case of a 60-year-old
patient requiring a full-arch, immediately loaded implant-supported mandibular
rehabilitation. A CAD/CAM-bone supported surgical template for osteoplasty was
used to develop a template for guided implant during an all-on-six immediate
loaded computer-aided implant surgery. The report describes the feasibility,
accuracy and usefulness of this double, CAD/CAM developed, surgical template.
PMID- 28702971
TI - History of venous leg ulcers.
AB - To retrieve the history of venous ulcers and of skin lesions in general, we must
go back to the appearance of human beings on earth. It is interesting to note
that cutaneous injuries evolved parallel to human society. An essential first
step in the pathogenesis of ulcers was represented by the transition of the
quadruped man to Homo Erectus. This condition was characterized by a greater
gravitational pressure on the lower limbs, with consequences on the peripheral
venous system. Furthermore, human evolution was characterized by an increased
risk of traumatic injuries, secondary to his natural need to create fire and hunt
(e.g. stones, iron, fire, animal fighting). Humans then began to fight one
another until they came to real wars, with increased frequency of wounds and
infectious complications. The situation degraded with the introduction of horse
riding, introduced by the Scites, who first tamed animals in the 7th century BC.
This condition exhibited iliac veins at compression phenomena, favouring the
venous stasis. With time, man continued to evolve until the modern age, which is
characterized by increased risk factors for venous wounds such as poor physical
activity and dietary errors (1, 2).
PMID- 28702972
TI - Laser treatment of post-thyroidectomy scar.
AB - A good aesthetic result in thyroid surgery is one of the main goals, as this
procedure usually involves young women affected in clearly visible anatomical
areas. To minimize the detrimental effects of scarring outcome, several
therapeutic options have been employed. Lasers may be an alternative choice for
prevention and treatment of post-surgical thyroidectomy scar. This paper reviews
literature and the current knowledge on this topic. A comprehensive search in the
Cochrane Library, MEDLINE and PUBMED databases was performed to identify relevant
literature investigating the role of laser therapy in both prevention and
treatment of unappealing scarring after thyroid surgery. Laser treatment of post
thyroidectomy scar is emerging with promising clinical outcomes. The greatest
efficacy has been seen with vascular-selective and ablative sources. Laser
therapy should be taken into account as it represents a valid and safe treatment
option.
PMID- 28702973
TI - Clinical and histological changes in Hidradenitis suppurativa following 1064 nm
nd:YAG intralesional laser treatment.
AB - Hidradenitis Suppurativa (HS) is recently attracting much attention and
awareness, often because it is misdiagnosed for years, restricting the
therapeutic options. Moreover, this pathology arises in areas such as the
inguinal region, that may cause embarrassment in young patients. Wrong diagnosis
and delay in appropriate treatments lead to an exacerbation of the symptoms and a
progression of the disease, which at the last stage can only be managed through
extensive surgical excisions, ablation and vaporization of nodules with CO2 laser
systems or aggressive chemotherapies such as anti-TNF-alpha like adalimumab
(Humira(r)-AbbVie Inc. North Chicago, Illinois USA). In our study, we present an
alternative low-invasive treatment that presents a successful outcome, supported
by clinical and histological evaluation, limited however only for early stages of
HS, highlighting the importance of raising awareness among physicians and
patients by stressing the importance of an early diagnosis.
PMID- 28702974
TI - Clinical evaluation of a new cosmetic cream containing PEPHA(r)-TIGHT on the skin
of childbearing women.
AB - The purpose of this study is to evaluate the efficacy of daily application of a
new cosmetic cream on the skin of childbearing women. Fifty-two childbearing
women were evaluated and each subject was initially (T0) prepared using an
hydration and sebometry test. A quantity of 50 ml of cosmetic cream was applied
for 1 month on each patient. At the end of the month (T1), the tests were
repeated. At the end of the study, all enrolled women showed an improvement of
facial skin hydration and sebum normalization and reduction of skin aging. The
present study shows that the cosmetic preparations containing PEPHA(r)-TIGHT and
other moisturizing agents are able to improve skin hydration and reduce skin
aging, according to several published clinical trials. The absence of a control
group and the short observation time limits this study.
PMID- 28702975
TI - Spontaneous retrospective clinical evaluation of a new phytoestrogen-based
cosmetic gel cream on postmenopausal women's skin.
AB - The purpose of this study is to evaluate the efficacy of daily application of a
new phytoestrogen-based cosmetic gel cream on postmenopausal women's skin. Sixty
postmenopausal women were evaluated. Each subject was initially (T0) submitted to
a hydration and sebometry test. A quantity of 50 ml of phytoestrogen-containing
gel cream was given for one month to each patient. At the end of the month (T1),
the tests were repeated. At the end of the study, 85% of the women showed an
improvement of facial skin hydration. All the women who took part in the study
had facial skin sebum normalization. The present study confirms that cosmetic
preparations containing phytoestrogen are able to reduce skin aging, according to
several published clinical trials. Nevertheless, the absence of a control group
and the short observation time limited this study.
PMID- 28702976
TI - A new hyaluronic acid polymer in the augmentation and restoration of labia
majora.
AB - Aesthetic surgery of female external genitalia has gained increasing popularity
over the past decade, with reduction of the labia minora (labiaplasty) being the
procedure most commonly requested and performed. Female external genitalia lose
elasticity and volume with age, but few studies describe the techniques for labia
majora augmentation. Currently, very few studies have investigated the
effectiveness and safety of labia majora augmentation with hyaluronic acid (HA)
injection. This study aims to evaluate the effectiveness and safety of labia
majora augmentation with hyaluronic acid filler injection. We retrospectively
analyzed 37 patients affected by hypotrophy of the labia majora, treated with HA
dermal filler 28mg/ml PEG crosslinked (Neauvia(r) Intense Rose, Matex Lab,
Switzerland) between May 2015 and July 2016. Global evaluation of the aesthetics
of the intimate area and clinical data were investigated with VAS (Visual
Analogic Scale) ad hoc. Adverse events and complications were recorded. A total
of 37 women affected by labia majora hypotrophy were treated with 28mg/ml HA
dermal filler. A significant clinical improvement was observed in the score
provided by both patients and doctor. Only mild adverse events and complications
were recorded. HA hydrogel with a novel crosslinking agent is able to provide a
considerable rejuvenation with a simple outpatient procedure and to bring a
significant clinical improvement. HA-based filler infiltration treatment in labia
majora is repeatable, has virtually no complications, and is reversible.
PMID- 28702977
TI - Laser treatment of leg ulcers: selected concepts.
AB - An overview on different laser devices, available for the treatment of the
different phases of wound healing: debridement, wound repair and scars
correction.
PMID- 28702978
TI - The evolution of artificial hair implantation.
AB - From the beginning, artificial hair implantation has aroused a lot of interest,
sometimes controversial, in the field of hair restoration. The artificial fiber
must be of high quality and biocompatible. Biofibre(r) is a very fine fiber
having diameter of 80 m. The standard length of this fiber is 15 or 30 cm, to
satisfy multiple patient requests. They are available in 13 colors and 3
different shapes (straight, wavy and curly). Artificial hair implant is indicated
in all (male and female) cases of androgenetic alopecia, especially for those who
show dismal response to medical therapies and have poor donor area supply for
hair transplantation. It has also shown good results to treat scars. One hundred
thirty-three cases of androgenetic alopecia were treated with Biofibre(r) and
followed-up for 3 years. A clinical evaluation was carried out after 1 month, 4
months and every other 4 months after the implant. The fiber loss was no more
than 10% per year in 91.4% of the cases, 15% in 7.8% of the cases and 20% in 0.8%
of the cases. 96.2% of patients declared themselves to be satisfied with the
result of the implant while 3.8% declared to be not satisfied. To conclude,
modern artificial hair implantation can be considered a safe and easy mode of
hair restoration, for male and female patients, especially in donor depleted
cases or when an immediate aesthetic result is required.
PMID- 28702979
TI - Use of platelet rich plasma in human infertility.
AB - Successful embryo implantation requires good quality embryo but also needs a
receptive endometrium site. In our clinical practice, we daily verify that an
adequate endometrial growth is reached for successful implantation. To understand
whether platelet rich plasma (PRP) can improve endometrium thickness and
performance, PRP treatment was carried out after at least three of the classic
medical protocols currently in use had been unsuccessfully adopted. Eight
patients with more than 3 cryo-transfers cancelled because of failure of
endometrial growth, defined as endometrium less than 6 mm, with negative
hysteroscopic screening for endometrial pathology, and with negative
bacteriologic screening, before present and all previous treatment, were selected
to undergo PRP treatment. In 7 out of 8 treatments, an endometrial thickness
greater than 6.5 mm (mean 6.9 mm) was reached, with endometrial three-layer
pattern, before progesterone administration and embryo transfer was performed. In
6 out of 7 patients, who underwent embryo transfer, beta-HCG were positive, with
2 biochemical abortions, one miscarriage at 6-week pregnancy, two babies born and
one drop-out. In this study, 8 patients had extraordinarily poor endometrial
quality, and the endometrium was non-responsive to conventional estrogenic
therapy, resulting in cycle cancellation. After application of PRP, the
endometrial thickness was satisfactory in all the patients except one. Of these,
beta-HCG was positive in 6 women, the pregnancy was progressing normally in 2
women, and one had an early miscarriage. We can suppose that the multiple
implantation failures were caused by inefficient expression adhesion molecules,
which can hypothetically be more represented after PRP application.
PMID- 28702980
TI - A short novel about the spread of two important diseases in history: syphilis and
SARS.
AB - Throughout the centuries, the undefended nature of man has very often manifested
in cases of epidemics, which have determined scenarios of suffering and death.
Through "historical" observation lens, it is possible to understand the
relationship between the spread of viruses, bacteria and parasites responsible
for these epidemics and the displacement of ancient or contemporary travellers.
We have analysed two infective diseases, syphilis and SARS, and their role in
history and in medicine.
PMID- 28702981
TI - Between history and gossip: the state of women relative to syphilis, a
traditionally male disease.
AB - Despite the new World Health Organization data remind us how syphilis is a
disease which affects both sexes equally, this pathology has always been mainly
considered a male disease. While several famous men are known to be affected by
syphilis, there are very few women affected by this pathology of which we have
historical records. Through the lives of Mary Todd Lincoln, Catherine of Aragon,
Karen Blixen and Florence Foster Jenkins, this article would like to grant
dignity to all the women who contracted syphilis in the wrong historical era
where, for a woman, admitting to contracting it was shameful. Through the
important women who lived their lives fighting against this disease and its
complications, we would like to pay tribute to all those women who still today,
in an era of antibiotics and where syphilis is a treatable pathology, they cannot
be cured because they are both geographically and socially disadvantaged.
PMID- 28702982
TI - Chronic inflammation therapy combined with low dose cytokines in the treatment of
chronic ulcers of lower limbs.
AB - Prevalence of chronic venous leg ulcers has increased from 55% to 75% in 10
years. We treat chronic vascular lesions according to a cyclic multiphase method
that follows the instrumental and differential etiologic diagnosis of ulcers of
the lower limbs. The AIMED (Anti Inflammatory Regenerative Medicine) operating
model follows the diagnostic phase and is structured in 5 interconnected phases.
Mare evaluation, pH control, biofilm removal and prevention and infections are
approached according to the International Guidelines. Low-dose cytokine therapy
to contrast the inflammatory process are administrated to the patients. Chronic
skin lesions of these patients, treated according to the AIMED protocol, have
been evaluated twice a week. The clinical evaluation parameters evaluated by us
were: reduction of pain at 15 and 30 days, reduction of 50% of the injury at 30
days, characteristics of perilesional skin (edema, erythema) and global profile
of the patient. The so-called Low Dose Cytokines therapy is changing the previous
therapeutic algorithms thanks to a safe and effective systemic cytokines
receptors interactive physiological process.
PMID- 28702983
TI - Photobiomodulation in the treatment of chronic non-responding wounds.
AB - We present a protocol of care and therapeutic approach to skin lesions, called
AIMED (Anti Inflammatory Regenerative Medicine), which is based on the
circularity of its phases and applied therapeutic methodologies. We used
photobiomodulation (PBM) for the examination non-responding skin lesions. PBM is
an adjuvant treatment for the stimulation of regenerative cellular processes,
reduction of inflammation and pain and biochemical modulation of molecular
response. We used PBM for the examination of skin lesions, which were not
responding to other therapies. LumiHealTM protocol treatment has been applied for
3 months on 8 patients affected by infected vascular ulcers of the lower limbs
resistant to previous treatments. Three patients reached positive results
immediately, and the remaining 5, at the first follow-up. The use of LumiHealTM
in combination with other treatments, method allowed an effective and rapid
improvement of the lesions via modulation of the immune response.
PMID- 28702984
TI - Regenerative medicine in the treatment of gastro-esophageal reflux disease and
laryngo-pharyngeal reflux. From research to cure.
AB - We present our observational study on 40 patients treated with the medical device
containing sodiumhyaluronic acid and magnesium alginate, performing a lubricating
and hydrating action. This deviceis in the form of a gel, with topical action to
contrast gastroesophageal reflux and to exert a mechanicalrole of protection of
the mucosal tissues (mouth-pharyngo-esophageal mucosa and gastric mucose.).
Fortypatients were recruited aged between 22- and 72-years-old with painful
dyspeptic Gastro EsophagealReflux Disease (GERD) symptomatology in acute or in
clinical phase (25 patients) and with pharyngolaryngo-tracheal symptomatology (15
patients). Patients were divided into two clinical groups: GroupA was treated
with the medical device, while Group B with conventional treatments without the
medicaldevice. Subjects of both groups were also treated with proton pump
inhibitors (PPIs). Follow-up was at10, 20 and 30 days and patients were evaluated
for reduction of their subjective symptoms, reduction ofsymptomatic and
occasional therapies, reduction of inflammatory process or disappearance of
epitheliallesions of the examined mucosa, healing process. The reduction of
subjective symptoms was observed at 10days in the patient with food bolus
(disappearance after 5 days) and in patients with a reduction of 70%. Arelevant
reduction in the use of symptomatic drugs was noted. Our data are relevant
considering symptomrelief (heartburn, reflux and dyspepsia). New scenarios for
the treatment of inflammatory diseases of thedigestive and respiratory tract
mucosa are at the horizon. Interdisciplinary translational research bringsto the
development of novel medical devices (as the one described in this study) with a
high safety profile,and extremely active on the inflammation-repair-regeneration
complex of different tissues and organs.
PMID- 28702985
TI - Photobiomodulation with polarized light in the treatment of cutaneous and mucosal
ulcerative lesions.
AB - In recent decades, regenerative medicine has achieved an important evolution at
both a conceptual level and scientific production, which explains the current and
future possibilities of therapy and daily clinical practice. The main aim of
regenerative medicine is the complex system of repair/regeneration. The current
literature on the subject demonstrates the advantage of visible light therapy for
skin injuries and diseases with the photobiomodulation in which light at low
energy levels modulates intra- and extra-cellular photoreceptors by molecular and
cellular processes that can stimulate both anti-inflammatory mechanisms and cell
proliferative response. The irradiation effects are activated soon after
exposure. The anti-inflammatory action on some classes of cytokines and cells
(e.g. mast cells and macrophages) is completed with the stimulation of the nitric
oxide production, which has an anti-inflammatory and vasodilation action, and
gives analgesic relief. Our attention focused on photobiomodulator medical device
emitting polarized light. 30 patients (19 women and 11 men) were enrolled in the
present study. They were treated for chronic lesions using Bioptron(r) Light
Therapy System device. Patients were initially subjected to Bioptron(r) light for
20 min after cleansing of the lesion. The operating protocol provides 24
sessions: twice per week for 12 weeks. Twenty patients have been studied for
symptoms, histological samples and ulcer characteristics. After 2 months, a
reduction of 50% of the lesions was recorded in 18 patients (60%), while in the
remaining patients a slower healing was observed. The total wound healing was
achieved after 3 months in 13 patients (43%). The examined parameters of the
symptom were exudation, pain and signs of infection. Results at 1 and 3 months
were, Exudation: at 1 month reduction and positive modulation was observed in 16
patients (53%) and in 25 patients at 3 months; Pain: (evaluated with Vas scale),
decreased in 21 patients at 1 month (70%) and in 100% of cases at 3 months;
Infections: regressed or disappeared in 100% of cases after the first month.
Today, it is no longer time for monotherapy applications, especially in
regenerative medicine and the adoption of biophysical therapies can play a
positive anti-inflammatory and regenerative role enhancing the function of non
invasive therapies.
PMID- 28702986
TI - Electromagnetic field in control tissue regeneration, pelvic pain, neuro
inflammation and modulation of non-neuronal cells.
AB - In scientific literature, magnetic fields are used both in basic science and
clinical research. They are often used to treat pain and neuro-inflammation
disorders thanks to their influence on cellular responses. Our project was born
from the regenerative support that we wanted to give to those diseases
characterized by neuro-inflammation, nerve lesion, muscles and tissues disorders
that can transform the symptom (e.g. neuropathic pelvic pain) in disease. In this
study, we examined the action of pulsed electromagnetic fields (PEMFs) on skin
lesion regeneration and the repetitive trans-pelvic magnetic stimulation (rTPMS)
on patients affected by incontinence and post-surgical problems, sexual
dysfunction, and pelvic pain. In rTPMS for post-surgery urinary incontinence, 40
patients affected by post-surgery urinary incontinence were enrolled. Twenty
patients (post-prostatectomy) were treated with rTPMS and 20 with conventional
therapies. In PEMF for the regeneration of skin tissue, 50 patients affected by
various types of skin lesions (70% low legs vascular lesions) were treated with
pulsed electromagnetic fields (PEMFs) twice per week and subsequently with home
treatment (Home Care device) twice per day. In rTPMS study, results were
evaluated after 3 months. In 10 patients (7 post prostatectomy, 3
cystourethrocele) which were submitted to 18 sessions, twice a week, an
improvement of incontinence in 75% of cases with patient compliance was recorded
and the quality of life up to 100% also improved. Utilizing PEMFs for the
regeneration of skin tissue, following 3 months of AIMED protocol treatment, we
reached a reduction of 50% of lesion area in the 60% of cases; 35% of cases
healed completely. The use of rTPMS allows training muscles to adequately respond
to inflammatory stimulus that causes muscle accommodation deficits with altered
contractility or spastic painful contracture in pelvic district. It also
stimulates a series of regenerative phenomena due to the action of magnetic waves
at high intensity on cellular membrane and cytoplasm, especially on mast cells,
which seem to have a fundamental role in the determination of the pelvic r egion
pain. The magnetic fields for the treatment of cutaneous lesions, which are
applied cyclically with other operating methods of AIMED protocol, confirmed the
literature data, with a treated group of 50 patients. The use of magnetic fields
opens new scenarios for regenerative medicine, since the cell could lend itself
to a self-healing process if it receives specific information.
PMID- 28702987
TI - Quality of life and psychological disturbances in adults with atopic dermatitis
in the Czech Republic.
AB - Atopic dermatitis (AD) leads to severe psychosocial disturbances that are quite
frequently underestimated. We evaluate the quality of life (QoL) of adult
patients with AD and their family members using DLQI, B-IPQ, FDLQI
questionnaires, observe psychopathological features with CAQ II questionnaire and
evaluate correlations between QoL, psychological disturbances and
objective/subjective parameters of disease severity. A reduction in QoL has been
proven by all questionnaires with statistically significant relationships between
all of them. The QoL of the patient (DLQI, B-IPQ) was found to be correlated to
FDLQI. We also confirmed statistically significant relationships between DLQI,
FDLQI, B-IPQ and objective severity of AD, as evaluated by SCORAD, in DLQI and
FDLQI also by TEWL, in B-IPQ also by IgE. All the QoL questionnaires have
statistically significant relationship to subjective symptoms (pruritus and sleep
disturbance). Interestingly, no significant relationship between QoL and age and
extent of eczema in visible localizations was found. CAQ II revealed high numbers
of psychological disturbances - the most often paranoia, hypochondria, suicidal
depression, anxiety and depression - and high prevalence of suicidal thoughts
(10.9%). Although AD is not life-threatening, its negative impact on the QoL of
adult patients and their family members/partners can be further influenced by
pathological personality traits of the patients.
PMID- 28702988
TI - Mesoporous SnO2 Nanotubes via Electrospinning-Etching Route: Highly Sensitive and
Selective Detection of H2S Molecule.
AB - We report the facile synthesis of thin-walled SnO2 nanotubes (NTs) with numerous
clustered pores (pore radius 6.56 nm) and high surface area (125.63 m2/g) via
selective etching of core (SiO2) region in SiO2-SnO2 composite nanofibers (NFs),
in which SnO2 phase preferentially occupies the shell while SiO2 is concentrated
in the center of the composite NFs. The SiO2-etched SnO2 NTs are composed of
ultrasmall crystallites (~6 nm in size) originating from crystal growth
inhibition by small SiO2 domains, which are partially segregated in the
polycrystalline SnO2 shell during calcination. These features account for
efficacious diffusion and innumerable active sites, which maximize interaction
between background gas (air) and analyte gas (H2S). Evaluation of gas-sensing
performance of the porous SnO2 NTs before and after decorating the exterior and
interior walls with Pt nanoparticles (NPs) reveals exceptional selectivity and
superior response (Ra/Rg) of 154.8 and 89.3 to 5 and 1 ppm of H2S, respectively.
Excellent gas-sensing characteristics are attributed to the porous topography,
nanosized crystallites, high surface area, and the catalytic activity of Pt/PtOx
NPs.
PMID- 28702989
TI - MoS2 Quantum Dots as New Electrochemiluminescence Emitters for Ultrasensitive
Bioanalysis of Lipopolysaccharide.
AB - Cd-based semiconductor quantum dots (QDs) with size-tunable luminescence and high
quantum yield have become the most promising electrochemiluminescence (ECL)
emitters. However, their unavoidable biotoxicity limited their applications in
bioassays. Here, the nontoxic and economical MoS2 QDs prepared by chemical
exfoliation from the bulk MoS2 were first investigated as new ECL emitters, and
then the possible luminescence mechanism of MoS2 QDs was studied using ECL
potential curves and differential pulse voltammetry (DPV) methods in detail. With
MoS2 QDs as the ECL emitters and triethylamine (TEA) as the efficient coreactant,
a practical and label-free aptasensor for lipopolysaccharide (LPS) detection was
constructed based on aptamer recognition-driven target-cycling synchronized
rolling circle amplification. Comparing to conventional stepwise reactions, this
target-cycling synchronized rolling circle amplification achieved more efficient
signal amplification and simpler operation. The developed assay for LPS detection
demonstrated a wide linear range of 0.1 fg/mL to 50 ng/mL with limit of detection
down to 0.07 fg/mL. It is worth mentioning that MoS2 QDs with stable ECL emission
exhibited a great application potential in ECL bioanalysis and imaging as a new
type of excellent emitter candidates.
PMID- 28702990
TI - Relationship between Amphipathic beta Structures in the beta1 Domain of
Apolipoprotein B and the Properties of the Secreted Lipoprotein Particles in McA
RH7777 Cells.
AB - Our previous studies demonstrated that the first 1000 amino acid residues (the
betaalpha1 domain) of human apolipoprotein (apo) B-100, termed apoB:1000, are
required for the initiation of lipoprotein assembly and the formation of a
monodisperse stable phospholipid (PL)-rich particle. The objectives of this study
were (a) to assess the effects on the properties of apoB truncates undergoing
sequential inclusion of the amphipathic beta strands in the 700 N-terminal
residues of the beta1 domain of apoB-100 and (b) to identify the subdomain in the
beta1 domain that is required for the formation of a microsomal triglyceride
transfer protein (MTP)-dependent triacylglycerol (TAG)-rich apoB-containing
particle. Characterization of particles secreted by stable transformants of McA
RH7777 cells demonstrated the following. (1) The presence of amphipathic beta
strands in the 200 N-terminal residues of the beta1 domain resulted in the
secretion of apoB truncates (apoB:1050 to apoB:1200) as both lipidated and lipid
poor particles. (2) Inclusion of residues 300-700 of the beta1 domain led to the
secretion of apoB:1300, apoB:1400, apoB:1500, and apoB:1700 predominantly as
lipidated particles. (3) Particles containing residues 1050-1500 were all rich in
PL. (4) There was a marked increase in the lipid loading capacity and TAG content
of apoB:1700-containing particles. (5) Only the level of secretion of apoB:1700
was markedly diminished by MTP inhibitor BMS-197636. These results suggest that
apoB:1700 marks the threshold for the formation of a TAG-rich particle and
support the concept that MTP participates in apoB assembly and secretion at the
stage where particles undergo a transition from PL-rich to TAG-rich.
PMID- 28702991
TI - Self-similar Hierarchical Wrinkles as a Potential Multifunctional Smart Window
with Simultaneously Tunable Transparency, Structural Color, and Droplet
Transport.
AB - Smart window has immense potential for energy savings in architectural and
vehicular applications, while most studies focus on the tunability of a single
property of optical transmittance. Here we explore harnessing dynamically tunable
hierarchical wrinkles for design of a potential multifunctional smart window with
combined structural color and water droplet transport control. The self-similar
hierarchical wrinkles with both nanoscale and microscale features are generated
on a prestrained poly(dimethylsiloxane) elastomer through sequential strain
release and multistep oxygen plasma treatment. We show that the hierarchically
wrinkled elastomer displays both opaqueness and iridescent structural color. We
find that restretching/releasing the elastomer leads to the reversible and
repeatable switch from opaqueness to transparency, arising from the flattening of
large wrinkles (micrometer scale), while a nonvanishing structural color occurs
due to the nondisappearing small wrinkles (nanoscale). The unique features of
combined reversible large wrinkles and irreversible small wrinkles during
hierarchical wrinkling are well reproduced by corresponding finite element
simulation. The criteria for generating self-similar hierarchical wrinkles is
revealed through a simplified theoretical model and validated by experiments. In
addition to its tunable optical property, we further show its ability in control
of water droplet transport on demand through mechanical stretching and release.
We find that an initially pinned water droplet on the tilted hierarchically
wrinkled surface starts to slide when the surface is stretched, and becomes
pinned again upon strain release. Such a process is reversible and repeatable.
The hierarchically wrinkled surface could find broad potential applications not
only in multifunctional smart windows with additional features of aesthetics and
water collection, but in microfluidics, design of slippery surfaces, and
directional water transportation.
PMID- 28702992
TI - Electrochromic Metallo-Organic Nanoscale Films: Fabrication, Color Range, and
Devices.
AB - In this study, we demonstrate a versatile approach for the formation of
electrochromic nanoscale assemblies on transparent conductive oxides on both
rigid and flexible substrates. Our method is based on the application of
alternating spin-coated layers of well-defined metal polypyridyl complexes and a
palladium(II) salt to form electrochemically addressable films with a high
chromophore density. By varying the central metal ion of the polypyridyl
complexes (Os, Ru, and Fe) and their ligands and by mixing these complexes,
coatings with a wide range of colors can be achieved. These coatings cover a
large area of RGB color space. The coloration intensities of these nanoscale
films can be tuned by the number of deposition steps. The materials have very
attractive ON/OFF ratios, electrochemical stabilities, and coloration
efficiencies. Reversible color-to-colorless and color-to-color transitions were
demonstrated, and the films were further integrated into sandwich cells.
PMID- 28702993
TI - Gold Nanorod Induced Warming of Embryos from the Cryogenic State Enhances
Viability.
AB - Zebrafish embryos can attain a stable cryogenic state by microinjection of
cryoprotectants followed by rapid cooling, but the massive size of the embryo has
consistently led to failure during the convective warming process. Here we
address this zebrafish cryopreservation problem by using gold nanorods (GNRs) to
assist in the warming process. Specifically, we microinjected the cryoprotectant
propylene glycol into zebrafish embryos along with GNRs, and the samples were
cooled at a rate of 90 000 degrees C/min in liquid nitrogen. We demonstrated the
ability to unfreeze the zebrafish rapidly (1.4 * 107 degrees C/min) by
irradiating the sample with a 1064 nm laser pulse for 1 ms due to the excitation
of GNRs. This rapid warming process led to the outrunning of ice formation, which
can damage the embryos. The results from 14 trials (n = 223) demonstrated viable
embryos with consistent structure at 1 h (31%) and continuing development at 3 h
(17%) and movement at 24 h (10%) postwarming. This compares starkly with 0%
viability, structure, or movement at all time points in convectively warmed
controls (n = 50, p < 0.001, ANOVA). Our nanoparticle-based warming process could
be applied to the storage of fish, and with proper modification, can potentially
be used for other vertebrate embryos.
PMID- 28702994
TI - Pore-Engineered Metal-Organic Frameworks with Excellent Adsorption of Water and
Fluorocarbon Refrigerant for Cooling Applications.
AB - Metal-organic frameworks (MOFs) have shown promising behavior for adsorption
cooling applications. Using organic ligands with 1, 2, and 3 phenylene rings, we
construct moisture-stable Ni-MOF-74 members with adjustable pore apertures, which
exhibit excellent sorption capabilities toward water and fluorocarbon R134a. To
our knowledge, this is the first report of adsorption isotherms of fluorocarbon
R134a in MOFs. The adsorption patterns for these materials differ significantly
and are attributed to variances in their hydrophobic/hydrophilic pore character
associated with differences in pore size.
PMID- 28702995
TI - Extreme Conductance Suppression in Molecular Siloxanes.
AB - Single-molecule conductance studies have traditionally focused on creating highly
conducting molecular wires. However, progress in nanoscale electronics demands
insulators just as it needs conductors. Here we describe the single-molecule
length-dependent conductance properties of the classic silicon dioxide insulator.
We synthesize molecular wires consisting of Si-O repeat units and measure their
conductance through the scanning tunneling microscope-based break-junction
method. These molecules yield conductance lower than alkanes of the same length
and the largest length-dependent conductance decay of any molecular systems
measured to date. We calculate single-molecule junction transmission and the
complex band structure of the infinite 1D material for siloxane, in comparison
with silane and alkane, and show that the large conductance decay is intrinsic to
the nature of the Si-O bond. This work highlights the potential for siloxanes to
function as molecular insulators in electronics.
PMID- 28702996
TI - Luciferase-Zinc-Finger System for the Rapid Detection of Pathogenic Bacteria.
AB - Rapid and reliable detection of pathogenic bacteria is crucial for food safety
control. Here, we present a novel luciferase-zinc finger system for the detection
of pathogens that offers rapid and specific profiling. The system, which uses a
zinc-finger protein domain to probe zinc finger recognition sites, was designed
to bind the amplified conserved regions of 16S rDNA, and the obtained products
were detected using a modified luciferase. The luciferase-zinc finger system not
only maintained luciferase activity but also allowed the specific detection of
different bacterial species, with a sensitivity as low as 10 copies and a linear
range from 10 to 104 copies per microliter of the specific PCR product. Moreover,
the system is robust and rapid, enabling the simultaneous detection of 6 species
of bacteria in artificially contaminated samples with excellent accuracy. Thus,
we envision that our luciferase-zinc finger system will have far-reaching
applications.
PMID- 28702997
TI - An Unconventional Zwitterionic Bolaamphiphile Containing PEG as Spacer Chain:
Surface Tension and Self-Assembly Behavior.
AB - Monolayer lipid membrane formation based on self-assembly of bolaamphiphiles
containing hydrophobic spacer are well-established in the literature, but
monolayer vesicle formation by so-called hydrophilic poly(ethylene glycol) (PEG)
spacer has not been reported to date. Here, a novel l-cysteine-derived
bolaamphiphile with PEG as spacer has been developed and characterized. The
interfacial properties and the solution behavior of the amphiphile were
investigated in pH 7.0 at 25 degrees C. The self-assembly properties of the
bolaamphiphile in aqueous buffer were investigated by using different techniques,
such as surface tensiometry, fluorescence spectroscopy, UV-vis spectroscopy,
isothermal titration calorimetry, dynamic light scattering, transmission electron
microscopy, and atomic force microscopy. Surprisingly, despite having so-called
polar spacer in between two polar head groups, it exhibits formation of
microstructures in aqueous buffer as well as in water at 25 degrees C. The
molecule undergoes self-organization leading to the formation of monolayer
vesicles with hydrodynamic diameters between 100 and 250 nm in a wide range of
concentration. The thermodynamic parameters clearly suggest that the aggregate
formation is mainly driven by the hydrophobic effect. The monolayer vesicles were
found to form at a very low concentration (>=0.63 mM) and within a wide pH range
(2-10). The vesicles exhibit excellent shelf life at physiological temperature.
PMID- 28702998
TI - Correction to Superparamagnetic Nanoparticles as High Efficiency Magnetic
Resonance Imaging T2 Contrast Agent.
PMID- 28702999
TI - Correction to Fluorinated and Charged Hydrogenated Alkanethiolates Grafted on
Gold: Expanding the Diversity of Mixed-Monolayer Nanoparticles for Biological
Applications.
PMID- 28703000
TI - druGAN: An Advanced Generative Adversarial Autoencoder Model for de Novo
Generation of New Molecules with Desired Molecular Properties in Silico.
AB - Deep generative adversarial networks (GANs) are the emerging technology in drug
discovery and biomarker development. In our recent work, we demonstrated a proof
of-concept of implementing deep generative adversarial autoencoder (AAE) to
identify new molecular fingerprints with predefined anticancer properties.
Another popular generative model is the variational autoencoder (VAE), which is
based on deep neural architectures. In this work, we developed an advanced AAE
model for molecular feature extraction problems, and demonstrated its advantages
compared to VAE in terms of (a) adjustability in generating molecular
fingerprints; (b) capacity of processing very large molecular data sets; and (c)
efficiency in unsupervised pretraining for regression model. Our results suggest
that the proposed AAE model significantly enhances the capacity and efficiency of
development of the new molecules with specific anticancer properties using the
deep generative models.
PMID- 28703001
TI - Synthesis and Structural Revision of the Fungal Tetramic Acid Metabolite
Spiroscytalin.
AB - Spiroscytalin, a natural 3-spirotetramic acid of hitherto uncertain absolute
configuration, was synthesized for the first time by a one-pot Knoevenagel-IMDA
reaction of an l-phenylalanine-derived tetramic acid and (R)-2-methyl-deca-6E,8E
dienal. Its absolute configuration was assigned by the known configurations of
the starting compounds and by NOESY correlations. Its identity with the natural
isolate was proved by the comparison of the NMR and circular dichroism spectra
and of the specific optical rotations. Its absolute configuration
(3R,5S,6S,7R,11S,14R) is enantiomeric to that originally proposed by the
isolating group. This natural isomer of spiroscytalin showed moderate activity
against Candida albicans and good activity against an export-deficient mutant of
Escherichia coli.
PMID- 28703002
TI - Sulfurization of Dissolved Organic Matter Increases Hg-Sulfide-Dissolved Organic
Matter Bioavailability to a Hg-Methylating Bacterium.
AB - Reactions of dissolved organic matter (DOM) with aqueous sulfide (termed
sulfurization) in anoxic environments can substantially increase DOM's reduced
sulfur functional group content. Sulfurization may affect DOM-trace metal
interactions, including complexation and metal-containing particle precipitation,
aggregation, and dissolution. Using a diverse suite of DOM samples, we found that
susceptibility to additional sulfur incorporation via reaction with aqueous
sulfide increased with increasing DOM aromatic-, carbonyl-, and carboxyl-C
content. The role of DOM sulfurization in enhancing Hg bioavailability for
microbial methylation was evaluated under conditions typical of Hg methylation
environments (MUM sulfide concentrations and low Hg-to-DOM molar ratios). Under
the conditions of predicted metacinnabar supersaturation, microbial Hg
methylation increased with increasing DOM sulfurization, likely reflecting either
effective inhibition of metacinnabar growth and aggregation or the formation of
Hg(II)-DOM thiol complexes with high bioavailability. Remarkably, Hg methylation
efficiencies with the most sulfurized DOM samples were similar (>85% of total Hg
methylated) to that observed in the presence of l-cysteine, a ligand facilitating
rapid Hg(II) biouptake and methylation. This suggests that complexes of Hg(II)
with DOM thiols have similar bioavailability to Hg(II) complexes with low
molecular-weight thiols. Overall, our results are a demonstration of the
importance of DOM sulfurization to trace metal and metalloid (especially mercury)
fate in the environment. DOM sulfurization likely represents another link between
anthropogenic sulfate enrichment and MeHg production in the environment.
PMID- 28703003
TI - The Long and the Short of It: Regiospecific Syntheses of Isomers of
Dicarbomethoxydibenzo-27-crown-9 and Binding Abilities of Their Pyridyl
Cryptands.
AB - The two isomers 6 and 9 of cis(4,4'-)-dicarbomethoxydibenzo-27-crown-9 with tri-
and tetra-(ethyleneoxy) linkages transposed were synthesized regiospecifically in
high yields (94 and 92%, respectively) by the Wang-Pederson-Wessels (WPW)
protocol and were converted via the corresponding diols 7 and 10 to the
corresponding pyridyl cryptands 3 and 4 by reaction with pyridine-2,6-dicarbonyl
chloride. As expected from Corey-Pauling-Koltun (CPK) models, the cryptand with
the tri(ethyleneoxy) arm para to the ester linkages, "short-armed" cryptand 3,
did display a higher binding constant (Ka = 2.4 * 105 M-1) with paraquats than
the analogous dibenzo-30-crown-10-based cryptand previously studied; however, the
effect was only twofold. Its binding to diquat was reduced by an order of
magnitude (1.5 * 105 M-1), as expected on the basis of its narrower cavity. Also
as expected, the cryptand with the tetra(ethyleneoxy) arm para to the ester
linkages, "long-armed" cryptand 4, possessed diminished binding with both
paraquats and diquat relative to the 30-crown-based analogue; in these systems,
2:1 H:G complexes were also detected by mass spectrometry. A crystal structure is
reported for 3.DQ(PF6)2.
PMID- 28703004
TI - Sialylglycan-Assembled Supra-Dots for Ratiometric Probing and Blocking of Human
Infecting Influenza Viruses.
AB - The seasonal outbreak of influenza causes significant morbidity and mortality
worldwide because a number of influenza virus (IV) strains have been shown to
infect and circulate in humans. Development of effective means to timely monitor
as well as block IVs is still a challenging task. Whereas conventional
fluorescence probes rely on a fluorimetric change upon recognizing IVs, here we
developed simple "Supra-dots" that are formed through the aqueous supramolecular
assembly between a blue-emitting polymer dot and red-emitting sialylglycan probes
for the ratiometric detection of IVs. Tuning the Forster resonance energy
transfer from polymer dots to glycan probes by selective sialylglycan-virus
recognition enables the fluorescence ratiometric determination of IVs, whereas
the presence of unselective, control viruses quenched the fluorescence of the
Supra-dots. Meanwhile, we show that the Supra-dots can effectively inhibit the
invasion of a human-infecting IV toward a human cell line, thereby making
possible a unique bifunctional, supramolecular probe for influenza theranostics.
PMID- 28703005
TI - Hierarchical NiO Cube/Nitrogen-Doped Reduced Graphene Oxide Composite with
Enhanced H2S Sensing Properties at Low Temperature.
AB - A novel hierarchical NiO cube (hc-NiO)/nitrogen-doped reduced graphene oxide (N
rGO) composite is synthesized via a facile hydrothermal method and a
postcalcination treatment without any templates and surfactants added. The NiO
cubes assembled by abundant nanoparticles in situ grow on the surface of N-rGO
layers. The combination of hc-NiO and N-rGO results in enhanced sensing
properties with the contributions of the N-rGO providing high specific surface
area and more efficient active sites for the adsorption of H2S molecules and the
hierarchically structured NiO cubes providing high sensitivity and distinctive
selectivity to H2S gas. At the optimal operating temperature of 92 degrees C,
the hc-NiO/N-rGO composite based sensor shows not only high response to H2S in a
range of 0.1-100 ppm but also excellent selectivity for H2S against the other
seven gases. The gaseous product, produced from the contact of H2S with the hc
NiO/N-rGO composite at 92 degrees C, is measured by GC-MS technique. The change
of the surface composition and the chemical state of the hc-NiO/N-rGO composite
before and after exposure to H2S are investigated by XPS. The possible sensing
mechanism of the hc-NiO/N-rGO composite is similar to that of semiconductor
oxides. The H2S molecules that absorbed on the sensor surface transform to SO2 by
reacting with the adsorbed oxygen anions. Meanwhile, the electrons restricted by
the surface-adsorbed oxygen return to the bulk and neutralize the holes,
producing a change in resistance.
PMID- 28703006
TI - How Do Organic Vapors Swell Ultrathin Films of Polymer of Intrinsic Microporosity
PIM-1?
AB - Dynamic sorption of ethanol and toluene vapor into ultrathin supported films of
polymer of intrinsic microporosity PIM-1 down to a thickness of 6 nm are studied
with a combination of in situ spectroscopic ellipsometry and in situ X-ray
reflectivity. Both ethanol and toluene significantly swell the PIM-1 matrix and,
at the same time, induce persistent structural relaxations of the frozen-in
glassy PIM-1 morphology. For ethanol below 20 nm, three effects were identified.
First, the swelling magnitude at high vapor pressures is reduced by about 30% as
compared to that of thicker films. Second, at low penetrant activities (below
0.3p/p0), films below 20 nm are able to absorb slightly more penetrant as
compared with thicker films despite a similar swelling magnitude. Third, for the
ultrathin films, the onset of the dynamic penetrant-induced glass transition Pg
has been found to shift to higher values, indicating higher resistance to
plasticization. All of these effects are consistent with a view where
immobilization of the superglassy PIM-1 at the substrate surface leads to an
arrested, even more rigid, and plasticization-resistant, yet still very open,
microporous structure. PIM-1 in contact with the larger and more condensable
toluene shows very complex, heterogeneous swelling dynamics, and two distinct
penetrant-induced relaxation phenomena, probably associated with the film outer
surface and the bulk, are detected. Following the direction of the penetrant's
diffusion, the surface seems to plasticize earlier than the bulk, and the two
relaxations remain well separated down to 6 nm film thickness, where they
remarkably merge to form just a single relaxation.
PMID- 28703007
TI - Chaperonin-Nanocaged Hemin as an Artificial Metalloenzyme for Oxidation
Catalysis.
AB - Taking inspiration from biology's effectiveness in functionalizing protein-based
nanocages for chemical processes, we describe here a rational design of an
artificial metalloenzyme for oxidations with the bacterial chaperonin GroEL, a
nanocage for protein folding in nature, by supramolecular anchoring of
catalytically active hemin in its hydrophobic central cavity. The promiscuity of
the chaperonin cavity is an essential element of this design, which can mimic the
hydrophobic binding pocket in natural metalloenzymes to accept cofactor and
substrate without requiring specific ligand-protein interactions. The success of
this approach is manifested in the efficient loading of multiple monomeric hemin
cofactors to the GroEL cavity by detergent dialysis and good catalytic oxidation
properties of the resulting biohybrid in tandem with those of the clean oxidant
of H2O2. Investigation of the mechanism of hemin-GroEL-catalyzed oxidation of two
model substrates reveals that the kinetic behavior of the complex follows a ping
pong mechanism in both cases. Through comparison with horseradish peroxidase, the
oxidative activity and stability of hemin-GroEL were observed to be similar to
those found in natural peroxidases. Adenosine 5'-triphosphate (ATP)-regulated
partial dissociation of the biohybrid, as assessed by the reduction of its
catalytic activity with the addition of the nucleotide, raises the prospect that
ATP may be used to recycle the chaperonin scaffold. Moreover, hemin-GroEL can be
applied to the chromogenic detection of H2O2, which (or peroxide in general) is
commonly contained in industrial wastes. Considering the rich chemistry of free
metalloporphyrins and the ease of production of GroEL and its supramolecular
complex with hemin, this work should seed the creation of many new artificial
metalloenzymes with diverse reactivities.
PMID- 28703008
TI - Satisficing in Mental Health Care Patients: The Effect of Cognitive Symptoms on
Self-Report Data Quality.
AB - Respondents may use satisficing (i.e., nonoptimal) strategies when responding to
self-report questionnaires. These satisficing strategies become more likely with
decreasing motivation and/or cognitive ability (Krosnick, 1991). Considering that
cognitive deficits are characteristic of depressive and anxiety disorders,
depressed and anxious patients may be prone to satisficing. Using data from the
Netherland's Study of Depression and Anxiety ( N = 2,945), we studied the
relationship between depression and anxiety, cognitive symptoms, and satisficing
strategies on the NEO Five-Factor Inventory. Results showed that respondents with
either an anxiety disorder or a comorbid anxiety and depression disorder used
satisficing strategies substantially more often than healthy respondents.
Cognitive symptom severity partly mediated the effect of anxiety disorder and
comorbid anxiety disorder on satisficing. The results suggest that depressed and
anxious patients produce relatively low-quality self-report data-partly due to
cognitive symptoms. Future research should investigate the degree of satisficing
across different mental health care assessment contexts.
PMID- 28703009
TI - Evaluating the Ecological Validity of the Dutch Eating Behavior Questionnaire
Among Obese Adults Using Ecological Momentary Assessment.
AB - This study evaluated the ecological validity (i.e., accurate measurement of a
construct as experienced in naturalistic settings) of the self-report Dutch
Eating Behavior Questionnaire (DEBQ). Obese adults ( N = 50) completed the DEBQ,
followed by a 2-week ecological momentary assessment protocol that included
measures of eating episodes and associated intrapersonal contextual factors.
Results revealed that DEBQ Emotional Eating was associated with greater negative
affect and less positive affect at both pre- and post-eating episode, as well as
post-eating ratings of feeling driven to eat. DEBQ External Eating was positively
associated with pre-eating expectations about enjoying the taste of food, but was
unrelated to actual enjoyment reported post-eating; External Eating was
positively associated with the post-eating ratings of feeling driven to eat. DEBQ
Dietary Restraint was positively associated with pre-eating intentions to eat
less to lose/avoid gaining weight. Overall, results provide some support for the
ecological validity of the DEBQ.
PMID- 28703010
TI - Validation of a Psychological Screening Algorithm for Predicting Spine Surgery
Outcomes.
AB - It is well established that psychological factors can affect spine surgery
results. A widely utilized presurgical psychological screening (PPS) algorithm
that combines established psychosocial risk factors to determine patients'
likelihood of achieving successful spine surgery results is evaluated in this
study. Patients ( n = 603) underwent a PPS, including a diagnostic interview,
psychometric testing, and review of medical records. The evaluator completed a
PPS algorithm for patients, placing them into one of five prognosis categories,
ranging from excellent to poor. For analysis purposes, these categories were
collapsed into three prognosis groups: Excellent, Good, and Fair to Very Poor.
Patients classified as having an Excellent prognosis achieved the best outcomes
following surgery, whereas those in the Fair to Very Poor category obtained the
worst results. Analyses of specific components of the PPS algorithm demonstrated
that algorithm items were modestly associated with reduced spine surgery results.
Implications for presurgical assessments of spine surgery candidates are
discussed.
PMID- 28703012
TI - Pathophysiology of the Peripheral Arterial Disease: Where Is the Paradox?
PMID- 28703011
TI - Psychopathic Personality Traits in the Military: An Examination of the Levenson
Self-Report Psychopathy Scales in a Novel Sample.
AB - The Levenson Self-Report Psychopathy Scale is a short, self-report measure
initially developed to assess psychopathic traits in noninstitutionalized
samples. The present study aimed to explore factor structure and convergent and
discriminant validity of the Levenson Self-Report Psychopathy Scale in a large
U.S. military sample (90.7% Army National Guard). Factor analytic data,
regression, and correlational analyses point to the superiority of Brinkley,
Diamond, Magaletta, and Heigel's three-factor model in this sample. Implications
for theory and the study of psychopathic personality traits in a military sample
are discussed.
PMID- 28703013
TI - Enhancing the fungicidal activity of antibiotics: are magnetic nanoparticles the
key?
PMID- 28703014
TI - Thrombin Receptor Agonist Peptide-Induced Platelet Aggregation Is Reduced in
Patients Receiving Dabigatran.
AB - : The availability of direct oral anticoagulants has caused a paradigm shift in
thrombosis management. The direct thrombin inhibitor dabigatran seems to obstruct
tenase complex by inhibiting thrombin generated in the initial phase and feed
back to the amplification phase of cell-based coagulation reactions. However, it
is still not fully understood if and how dabigatran impact platelet function.
This observational study aimed to assess in vitro platelet function in patients
with atrial fibrillation receiving dabigatran. Platelet aggregability was tested
with platelet-rich plasma using platelet aggregometry (PACKS-4 aggregometer).
Blood samples were stimulated with thrombin receptor agonist peptide (TRAP; 32
MUmol/L). RESULTS: A total of 28 patients with nonvalvular atrial fibrillation
were enrolled. The mean age was 71.57 (9.75) years (range: 50-87 years), 16
patients were women, and the mean CHA2DS2VASc score was 3.93 (1.41). All patients
began treatment with dabigatran as initial anticoagulant treatment. The minimum
term use of dabigatran was 18 days. Dabigatran doses were 110 mg (57.14%) or 150
mg (42.86%) twice daily. The TRAP-induced platelet aggregation was significantly
lower 2 hours after taking dabigatran compared to baseline value (79.39 [13.38]
vs 90.14 [10.5]). CONCLUSION: The TRAP-induced platelet aggregation was reduced
in cardiovascular patients 2 hours after receiving dabigatran. Our findings could
have some important clinical implications because platelet aggregation and
coagulation cascade are affected at the same time.
PMID- 28703015
TI - Guidelines for the Pharmacotherapy of Schizophrenia in Adults.
AB - OBJECTIVE: The present guidelines address the pharmacotherapy of schizophrenia in
adults across different stages, phases, and symptom domains. METHOD: Guidelines
were developed using the ADAPTE process, which takes advantage of existing
guidelines. Six guidelines were identified for adaptation, with recommendations
extracted from each. For those specific to the pharmacotherapy of schizophrenia
in adults, a working group selected between guidelines and recommendations to
create an adapted guideline. RESULTS: Recommendations can be categorized into 6
areas that include 1) first-episode schizophrenia, 2) acute exacerbation, 3)
relapse prevention and maintenance treatment, 4) treatment-resistant
schizophrenia, 5) clozapine-resistant schizophrenia, and 6) specific symptom
domains. For each category, recommendations are made based on the available
evidence, which is discussed and linked to other established guidelines.
CONCLUSIONS: In most cases, evidence-based recommendations are made that can be
used to guide current clinical treatment and decision making. Notably, however,
there is a paucity of established evidence to guide treatment decision making in
the case of clozapine-resistant schizophrenia, a subsample that represents a
sizable proportion of those with schizophrenia.
PMID- 28703016
TI - Strategies for Preventing Cognitive Decline in Healthy Older Adults.
AB - OBJECTIVE: Many advances have been made in the understanding of age-related
changes in cognition. As research details the cognitive and neurobiological
changes that occur in aging, there is increased interest in developing and
understanding methods to prevent, slow, or reverse the cognitive decline that may
occur in normal healthy older adults. The Institute of Medicine has recently
recognized cognitive aging as having important financial and public health
implications for society with the increasing older adult population worldwide.
Cognitive aging is not dementia and does not result in the loss of neurons but
rather changes in neurotransmission that affect brain functioning. The fact that
neurons are structurally intact but may be functionally affected by increased age
implies that there is potential for remediation. METHOD AND RESULTS: This review
article presents recent work using medication-based strategies for slowing
cognitive changes in aging. The primary method presented is a hormonal approach
for affecting cognition in older women. In addition, a summary of the work
examining modifiable lifestyle factors that have shown promise in benefiting
cognition in both older men and women is described. CONCLUSIONS: Much work
remains to be done so that evidence-based recommendations can be made for slowing
cognitive decline in healthy older adults. The success of some of these methods
thus far indicates that the brains of healthy older adults are plastic enough to
be able to respond to these cognitive decline prevention strategies, and further
work is needed to define the most beneficial methods.
PMID- 28703017
TI - Canadian Treatment Guidelines on Psychosocial Treatment of Schizophrenia in
Adults.
AB - OBJECTIVE: It is generally recognised that psychosocial interventions are
essential components of the effective treatment of schizophrenia in adults. A
considerable body of research is being published regarding the effectiveness of
such interventions. In the current article, we derive recommendations reflecting
the current state of evidence for their effectiveness. METHODS: Recommendations
were formulated on the basis of a review of relevant guidelines, particularly
those formulated by the Scottish Intercollegiate Guideline Network (SIGN) and
National Institute for Health and Care Excellence (NICE). RESULTS: There is
evidence strongly supporting the use of family interventions, supported
employment programs, and cognitive-behavioural therapy. There are also reasons to
recommend the use of cognitive remediation, social skills training, and life
skills training under specified circumstances. It is important that all patients
and families be provided with education about the nature of schizophrenia and its
treatment. Several recent innovative psychosocial approaches to treatment are
awaiting more thorough evaluation. CONCLUSIONS: There continues to be strong
evidence for the effectiveness of several psychosocial interventions in improving
outcomes for adults with schizophrenia. In the past decade, innovative
interventions have been described, several of which are the subject of ongoing
evaluative research.
PMID- 28703018
TI - Comparative Effectiveness of Structural versus Regulatory Protein Gene Transfer
on Articular Chondrocyte Matrix Gene Expression.
AB - Objective The production of extracellular matrix is a necessary component of
articular cartilage repair. Gene transfer is a promising method to improve matrix
biosynthesis by articular chondrocytes. Gene transfer may employ transgenes
encoding regulatory factors that stimulate the production of matrix proteins, or
may employ transgenes that encode the proteins themselves. The objective of this
study was to determine which of these 2 approaches would be the better choice for
further development. We compared these 2 approaches using the transgenes encoding
the structural matrix proteins, aggrecan or type II collagen, and the transgene
encoding the anabolic factor, insulin-like growth factor I (IGF-I). Methods We
transfected adult bovine articular chondrocytes with constructs encoding type II
collagen, aggrecan, or IGF-I, and measured the expression of type II collagen (
COL2A1) and aggrecan ( ACAN) from their native genes and from their transgenes.
Results IGF-I gene ( IGF1) transfer increased the expression of the native
chondrocyte COL2A1 and ACAN genes 2.4 and 2.9 times control, respectively. COL2A1
gene transfer did not significantly increase COL2A1 transcripts, even when the
transgene included the genomic COL2A1 regulatory sequences stimulated by
chondrogenic growth factors. In contrast, ACAN gene transfer increased ACAN
transcripts up to 3.4 times control levels. IGF1, but not ACAN, gene transfer
increased aggrecan protein production. Conclusion Taken together, these results
suggest that the type II collagen and aggrecan production required for articular
cartilage repair will be more effectively achieved by genes that encode anabolic
regulatory factors than by genes that encode the matrix molecules themselves.
PMID- 28703019
TI - Effectiveness and Safety of Magnesium Replacement in Critically Ill Patients
Admitted to the Medical Intensive Care Unit in an Academic Medical Center: A
Retrospective, Cohort Study.
AB - BACKGROUND: "Rules of thumb" for the replacement of electrolytes, including
magnesium, in critical care settings are used, despite minimal empirical
validation of their ability to achieve a target serum concentration. This study's
purpose was to evaluate the effectiveness and safety surrounding magnesium
replacement in medically, critically ill patients with mild-to-moderate
hypomagnesemia. METHODS: This was a single-center, retrospective, observational
evaluation of episodes of intravenous magnesium replacement ordered for patients
with mild-to-moderate hypomagnesemia (1.0-1.9 mEq/L) admitted to a medical
intensive care unit from May 2014 to April 2016. The primary effectiveness
outcome, achievement of target serum magnesium concentration (>=2 mEq/L) compared
to expected achievement using a "rule of thumb" estimation that 1 g intravenous
magnesium sulfate raises the magnesium concentration 0.15 mEq/L, was tested using
1-sample z test. Logistic regression analysis was conducted to assess the effect
of infusion rate on target achievement. RESULTS: Of 152 days on which magnesium
replacements were provided for 72 patients, a follow-up serum magnesium
concentration was checked within 24 hours in 89 (58.6%) episodes. Of these 89
episodes, serum magnesium concentration reached target in only 49 (59.8%)
episodes compared to an expected 89 (100%; P < .0001). There was no significant
association between infusion rate and achievement of the target serum magnesium
concentration (odds ratio: 0.962, 95% confidence interval: 0.411-2.256).
CONCLUSIONS: Medically, critically ill patients who received nonprotocolized
magnesium replacement achieved the target serum magnesium concentration less
frequently than the "rule of thumb" estimation predicted.
PMID- 28703020
TI - Epidemiology and clinical outcomes of snakebite in the elderly: a ToxIC database
study.
AB - INTRODUCTION: Epidemiologic studies of snakebites in the United States report
typical victims to be young men. Little is known regarding other demographics
including children and the elderly. The objective of this study was to describe
the epidemiology and clinical manifestations of snake bite in elderly patients
reported to the ToxIC (Toxicology Investigators Consortium) North American
Snakebite Registry (NASBR) Methods: This was a multicenter analysis of a
prospectively collected cohort of patients with snakebite reported to the ToxIC
NASBR between 1 January 2013 and 31 December 2015. Inclusion criterion was age
>65. Variables collected included patient demographics, medical comorbidities,
medications, date the case was reported to the registry, location of exposure,
bite location, snake species, clinical manifestations, outcomes, and management.
RESULTS: Of the 450 cases reported, 30 (6.7%) occurred in elderly patients, with
an average age of 74 years. Rattlesnake envenomations were common (93.3%). The
majority of patients were men (66.7%) and reported at least one medical
comorbidity (83.3%). Most patients were on cardiac medications (60%) and use of
antiplatelet or anticoagulant medications was common (33%). Hemotoxicity occurred
in 30% of patients on initial presentation and 11.5% of patients on initial
follow-up. No clinically significant early or late bleeding was observed.
CONCLUSIONS: Elderly patients with North American snake envenomation are likely
to have co-morbidities and to take medications that may increase their risk for
hemotoxicity, however risk of bleeding or other complications was not increased
in this group.
PMID- 28703021
TI - Prediction of pesticide acute toxicity using two-dimensional chemical descriptors
and target species classification.
AB - Previous modelling of the median lethal dose (oral rat LD50) has indicated that
local class-based models yield better correlations than global models. We
evaluated the hypothesis that dividing the dataset by pesticidal mechanisms would
improve prediction accuracy. A linear discriminant analysis (LDA) based-approach
was utilized to assign indicators such as the pesticide target species, mode of
action, or target species - mode of action combination. LDA models were able to
predict these indicators with about 87% accuracy. Toxicity is predicted utilizing
the QSAR model fit to chemicals with that indicator. Toxicity was also predicted
using a global hierarchical clustering (HC) approach which divides data set into
clusters based on molecular similarity. At a comparable prediction coverage
(~94%), the global HC method yielded slightly higher prediction accuracy (r2 =
0.50) than the LDA method (r2 ~ 0.47). A single model fit to the entire training
set yielded the poorest results (r2 = 0.38), indicating that there is an
advantage to clustering the dataset to predict acute toxicity. Finally, this
study shows that whilst dividing the training set into subsets (i.e. clusters)
improves prediction accuracy, it may not matter which method (expert based or
purely machine learning) is used to divide the dataset into subsets.
PMID- 28703022
TI - Lumbar idiopathic intervertebral disc calcification associated with ossification
of the ligamentum flavum in adult: a case report.
AB - A 23 year-old female was diagnosed with lumbar idiopathic intervertebral disc
calcification associated with ossification of OLF. The patient underwent
posterior decompression and posterolateral fusion with pedicle screw fixation,
which achieved excellent clinical improvement. Surgical intervention of a
posterior approach for decompression and instrumented fusion is indicated in
cases that the spinal cord compression with neurologic deficits was involved.
PMID- 28703023
TI - Insuring spinal neurosurgery.
PMID- 28703024
TI - Safety and effectiveness of physostigmine: a 10-year retrospective review.
AB - BACKGROUND: Physostigmine has long been recognized as an antidote to reverse
anticholinergic delirium. However, its effectiveness, safety profile, and dosing
have been disputed. OBJECTIVES: To describe effectiveness, adverse events, and
dosing associated with the use of physostigmine to reverse anticholinergic
delirium. METHODS: A retrospective cohort study of hospitalized patients reported
to a regional poison center system between 2003 and 2012 who received
physostigmine to reverse an anticholinergic toxidrome. Data extraction of a
priori defined variables were recorded with concurrence of investigators. The
cases were stratified by the primary ingestant as the presumed causative agent
and associations for response were performed using odds ratios (ORs), 95%
confidence intervals (CI's), and p values. RESULTS: Of the 1422 cases identified,
191 met the inclusion criteria. Patients exposed to non-diphenhydramine
antihistamines (n = 14), antipsychotics (n = 4), and tricyclic antidepressants (n
= 3) had 100% response to physostigmine, whereas anticholinergic plants (n =
46/67; 68.7%, OR: 0.70; CI: 0.36-1.35), diphenhydramine (n = 43/56; 64.2%, OR:
1.30; CI: 0.63-2.68), and combination products (n = 8/10; 80%, OR: 1.48; CI: 0.30
7.24) had partial response rates. Of the included patients, 142 (74.3%) were
treated with physostigmine alone, and 16 (8.4%) of these patients were discharged
directly from the emergency department (ED). DISCUSSION: Most patients, 182
(95.3%), had no documented adverse effects. Four patients (2.1%) experienced
emesis, two experienced QTc prolongation (1.0%), and two experienced seizures
(1.0%). There was a single fatality 6 h after physostigmine administration.
Average initial total doses of physostigmine ranged from 1.0 to 1.75 mg. Most
patients were admitted to the ICU (n = 110; 57.6%), however, 36 (18.8%) patients
were discharged directly from the ED. CONCLUSIONS: In this retrospective cohort
study, physostigmine administration to reverse anticholinergic delirium had a
good safety profile, and often improved or resolved anticholinergic delirium when
administered in doses less than 2 mg.
PMID- 28703025
TI - Patient Satisfaction of Pharmacist-Provided Care via Clinical Video
Teleconferencing.
AB - PURPOSE: Patient satisfaction with the use of telehealth in disease state
management provided by pharmacists has not been fully studied. We hypothesized
that patient satisfaction with pharmacist-provided consultations via clinical
video teleconferencing (CVT) would not differ from face-to-face delivery.
METHODS: Patients were recruited from 2 primary care provider sites from
September 2015 to May 2016. Patients completed a survey to evaluate their
satisfaction and quality of provider-patient communication with the method in
which consultation with a pharmacist was provided. The survey was a 10-item,
patient self-reported questionnaire. The primary outcome evaluated patients'
scores on assessment of the provider's use of patient-centered communication. The
secondary outcome evaluated patients' scores on assessment of the provider's
clinical competence and skills and interpersonal skills. RESULTS: There were a
total of 57 surveys collected. For both the primary outcome and secondary
outcome, over 80% of collected responses for each question in both clinics were
scored a 5 that indicates patients were very satisfied with the provider's use of
patient-centered communication and clinical competence and skills. For both the
primary and secondary outcomes, there were no statistically significant
differences in patients' scores that assessed provider's use of patient-centered
communication nor the provider's clinical competence and skill. CONCLUSION: The
results of this study indicate patients are satisfied with pharmacists' use of
patient-centered communication and clinical competence and skills via both CVT
and face-to-face consultations supporting our research hypothesis that patient
satisfaction with care provided via CVT did not differ from face-to-face provided
care.
PMID- 28703026
TI - Placental transfer of tyrosine kinase inhibitors used for chronic myeloid
leukemia treatment.
AB - Both favorable pregnancy outcomes and fetal abnormalities have been associated
with the use of tyrosine kinase inhibitors (TKIs) during pregnancy. The placental
transfer of TKIs in humans is poorly understood. We observed women with chronic
myeloid leukemia who used imatinib or nilotinib during the late pregnancy stages.
The newborns had no birth abnormalities. We evaluated the drug concentrations in
maternal blood, umbilical cord blood, and placental samples collected during
labor. We found limited placental transfer of the TKIs. The fetal/maternal
concentration ratio ranged from 0.5 to 0.58 for nilotinib and from 0.05 to 0.22
for imatinib. The placental/maternal ratio was higher for imatinib than for
nilotinib. Theoretical pharmacokinetic modeling of passive placental crossing was
insufficient to predict the in vivo data because the calculated fetal/maternal
ratio was close to 1 for both drugs. We propose that active placental transport
contributes to fetal protection against TKI exposure during pregnancy.
PMID- 28703027
TI - Life-course determinants of cognitive reserve (CR) in cognitive aging and
dementia - a systematic literature review.
AB - OBJECTIVES: The concept of cognitive reserve (CR) is defined as a moderator,
which allows an individual to preserve cognition despite underlying brain
pathology. There is no consensus of what potentially modifiable CR determinants
are of greatest importance. The aim of this review was to identify life-course
factors which protect older individuals from expressing cognitive decline despite
the presence of brain pathology. METHOD: A systematic review search was performed
in MEDLINE (1946-06/09/13), EMBASE (1947-06/09/13), and PsycheInfo (1967
06/09/13). We included studies examining CR in the context of the four commonest
subtypes of dementia, mild cognitive impairment or healthy aging. Studies which
combined measurement of underlying dementia-related neuropathology, cognitive
function, and factors providing CR in a single model were accepted. We performed
a qualitative synthesis of the results. RESULTS: Thirty-four studies out of 9229
screened records met our inclusion criteria and were therefore quality assessed
and data extracted. Variation in CR definition made comparison across studies
difficult. One hundred and forty-four out of 156 models examined education and
occupation: overall, 58% of eligible models classified education and 60%
occupation as a CR determinant, with 12% and 44% of those, respectively, being of
high quality. Within healthy population suitable to inform preventative
interventions, there was consistent evidence for education having a protective
effect on general cognition in the face of multiple brain burden measures, while
occupation presented inconclusive results within cognitive groups. CONCLUSIONS:
Further research on modifiable determinants of CR beyond education/occupation
including early-life factors and consensus on CR definition are warranted.
PMID- 28703028
TI - The SAL-PAP Chloroplast Retrograde Pathway Contributes to Plant Immunity by
Regulating Glucosinolate Pathway and Phytohormone Signaling.
AB - Chloroplasts have a crucial role in plant immunity against pathogens. Increasing
evidence suggests that phytopathogens target chloroplast homeostasis as a
pathogenicity mechanism. In order to regulate the performance of chloroplasts
under stress conditions, chloroplasts produce retrograde signals to alter nuclear
gene expression. Many signals for the chloroplast retrograde pathway have been
identified, including chlorophyll intermediates, reactive oxygen species, and
metabolic retrograde signals. Although there is a reasonably good understanding
of chloroplast retrograde signaling in plant immunity, some signals are not well
understood. In order to understand the role of chloroplast retrograde signaling
in plant immunity, we investigated Arabidopsis chloroplast retrograde signaling
mutants in response to pathogen inoculation. sal1 mutants (fry1-2 and alx8)
responsible for the SAL1-PAP retrograde signaling pathway showed enhanced disease
symptoms not only to the hemibiotrophic pathogen Pseudomonas syringae pv. tomato
DC3000 but, also, to the necrotrophic pathogen Pectobacterium carotovorum subsp.
carotovorum EC1. Glucosinolate profiles demonstrated the reduced accumulation of
aliphatic glucosinolates in the fry1-2 and alx8 mutants compared with the wild
type Col-0 in response to DC3000 infection. In addition, quantification of
multiple phytohormones and analyses of their gene expression profiles revealed
that both the salicylic acid (SA)- and jasmonic acid (JA)-mediated signaling
pathways were down-regulated in the fry1-2 and alx8 mutants. These results
suggest that the SAL1-PAP chloroplast retrograde pathway is involved in plant
immunity by regulating the SA- and JA-mediated signaling pathways.
PMID- 28703029
TI - Hop stunt viroid: Effect on Host (Humulus lupulus) Transcriptome and Its
Interactions With Hop Powdery Mildew (Podospheara macularis).
AB - Viroids are the smallest known plant pathogens that exploit host systems for
their replication and cause diseases in many hosts. In this study, the host
response of hop plants to Hop stunt viroid (HSVd) infection was studied through
transcriptome analysis. RNA sequence analysis of hop leaves infected with HSVd
revealed dynamic changes in hop gene expression. Defense-related genes and genes
involved in lipid and terpenoid metabolism are the major categories that showed
differential expression due to HSVd infection. Additionally, the effect of HSVd
on development of hop powdery mildew (Podospheara macularis) (HPM) was studied.
Transcriptome analysis followed by quantitative reverse transcription-polymerase
chain reaction analysis showed that transcript levels of pathogenesis-related
(PR) genes such as PR protein 1, chitinase, and thaumatin-like protein genes are
induced in leaves infected with HPM alone. The response in these genes to HPM is
significantly down-regulated in leaves with HSVd-HPM mixed infection. These
results confirm that HSVd alters host metabolism, physiology, and plant defense
responses. Nevertheless, in detached leaf assays, HPM consistently expanded
faster on HSVd-negative leaves relative to HSVd-positive leaves. Although HSVd
infection suppresses elements associated with the host immunity response,
infection by HSVd is antagonistic to HPM infection of hops.
PMID- 28703030
TI - Cartilage Health in Knees Treated with Metal Resurfacing Implants or Untreated
Focal Cartilage Lesions: A Preclinical Study in Sheep.
AB - Background Full-depth cartilage lesions do not heal and the long-term clinical
outcome is uncertain. In the symptomatic middle-aged (35-60 years) patient,
treatment with metal implants has been proposed. However, the cartilage health
surrounding these implants has not been thoroughly studied. Our objective was to
evaluate the health of cartilage opposing and adjacent to metal resurfacing
implants. Methods The medial femoral condyle was operated in 9 sheep bilaterally.
A metallic resurfacing metallic implant was immediately inserted into an
artificially created 7.5 mm defect while on the contralateral knee the defect was
left untreated. Euthanasia was performed at 6 months. Six animals, of similar age
and study duration, from a previous study were used for comparison in the
evaluation of cartilage health adjacent to the implant. Cartilage damage to joint
surfaces within the knee, cartilage repair of the defect, and cartilage adjacent
to the implant was evaluated macroscopically and microscopically. Results Six
animals available for evaluation of cartilage health within the knee showed a
varying degree of cartilage damage with no statistical difference between defects
treated with implants or left untreated ( P = 0.51; 95% CI -3.7 to 6.5). The
cartilage adjacent to the implant (score 0-14; where 14 indicates no damage)
remained healthy in these 6 animals showing promising results (averaged 10.5;
range 9-11.5, SD 0.95). Cartilage defects did not heal in any case. Conclusion
Treatment of a critical size focal lesion with a metal implant is a viable
alternative treatment.
PMID- 28703031
TI - Lower circulating migration inhibitory factor protein is associated with
metabolic syndrome and diabetes.
AB - AIM: The controversial relationship between macrophage migration inhibitory
factor (MIF) and the likelihood of cardiometabolic diseases was investigated.
Results/methodology: Assayed MIF protein from 1225 adults was cross-sectionally
analyzed. MIF was independently inversely associated with age, total testosterone
and positively with high-density lipoprotein-cholesterol. In men MIF correlation
with age, testosterone and waist circumference converted from inverse in the
upper to positive in the bottom MIF third. Both metabolic syndrome and diabetes
were significantly associated, in combined gender, with the intermediate (vs the
highest) MIF tertile at an odds ratio 1.6. Coronary heart disease was not
significantly related with MIF in either gender. DISCUSSION/CONCLUSION: Findings
are consistent with oxidative damage to MIF protein and its involvement in
autoimmune activation, likely more extensive in women.
PMID- 28703032
TI - Cerbera manghas poisoning survived by using extracorporeal life support.
PMID- 28703033
TI - The Attitudes About Parenting Strategies for Anxiety Scale: A Measure of
Parenting Attitudes About Protective and Intrusive Behavior.
AB - Protective and intrusive parenting behaviors consistently relate to children's
anxiety development. We present two studies describing the development of the
Attitudes about Parenting Strategies for Anxiety (APSA) scale, which assesses
parent distress about children's displays of anxiety and shyness as well as
parent attitudes about the effectiveness of protective and intrusive responses
across several domains. Study 1 included 594 parents who completed the APSA and
additional measures online and established the factor structure, internal
reliability, and validity of the measure. We also performed a latent profile
analysis of the attitude items to understand common patterns and their
correlates. Study 2 comprised 108 mothers participating in a laboratory-based
study and provided additional evidence for the factor structure, reliability, and
validity, as well as 1-year stability. The APSA appears to be a reliable and
valid measure that could have utility for understanding the determinants of
parenting behaviors relevant to child anxiety development.
PMID- 28703034
TI - The impact of maternal nausea and vomiting in pregnancy on expectant fathers:
findings from the Australian Fathers' Study.
AB - INTRODUCTION: Nausea and vomiting in pregnancy (NVP) are common. Whilst the
impact on pregnant women has been well documented, there is less data on the
impact on partners. This study evaluated awareness and impact of maternal NVP on
expectant fathers. METHODS: Observational study of 300 expectant fathers.
Institutional ethics approval and consent were obtained. Fathers were recruited
from antenatal clinics and community settings. Researchers administered
demographic, attitudinal and the Hospital Anxiety and Depression scale
questionnaires during the third trimester. Expectant fathers were asked if their
partner experienced NVP. If aware, they were asked to comment upon the impact on
their lives. RESULTS: Participants were similar in demographics to those of the
wider Australian community of expectant fathers. Most fathers were aware whether
their partner experienced NVP (82%). Of these fathers, 20% reported no NVP, and
30%, 37% and 13% men reported maternal NVP was mild, moderate and severe,
respectively. There was no correlation between paternal depression and maternal
NVP, but a significant association was found between moderate and severe maternal
NVP and paternal anxiety. In qualitative comments, five themes emerged:
disruption on work, feelings of frustration and helplessness, concern over
depression in their partner, concern for the developing baby and a sense of being
manipulated in the third trimester of pregnancy. DISCUSSION: Most expectant
fathers are aware of NVP in their partner. Moderate and severe maternal NVP are
associated with significantly higher symptoms of paternal anxiety.
PMID- 28703035
TI - Influence of body composition on physiological responses to post-exercise
hydrotherapy.
AB - This study examined the influence of body composition on temperature and blood
flow responses to post-exercise cold water immersion (CWI), hot water immersion
(HWI) and control (CON). Twenty-seven male participants were stratified into
three groups: 1) low mass and low fat (LM-LF); 2) high mass and low fat (HM-LF);
or 3) high mass and high fat (HM-HF). Experimental trials involved a standardised
bout of cycling, maintained until core temperature reached 38.5 degrees C.
Participants subsequently completed one of three 15-min recovery interventions
(CWI, HWI, or CON). Core, skin and muscle temperatures, and limb blood flow were
recorded at baseline, post-exercise, and every 30 min following recovery for 240
min. During CON and HWI there were no differences in core or muscle temperature
between body composition groups. The rate of fall in core temperature following
CWI was greater in the LM-LF (0.03 +/- 0.01 degrees C/min) group compared to the
HM-HF (0.01 +/- 0.001 degrees C/min) group (P = 0.002). Muscle temperature
decreased to a greater extent during CWI in the LM-LF and HM-LF groups (8.6 +/-
3.0 degrees C) compared with HM-HF (5.1 +/- 2.0 degrees C, P < 0.05). Blood flow
responses did not differ between groups. Differences in body composition alter
the thermal response to post-exercise CWI, which may explain some of the variance
in the responses to CWI recovery.
PMID- 28703036
TI - An unusual presentation of ischaemic mitral regurgitation as P2 prolapse.
AB - A 54-year-old gentleman presented with pulmonary oedema secondary to
anterolateral papillary muscle (PPM) rupture and acute mitral regurgitation
subsequent to myocardial ischaemia (MI). Angiography revealed complete occlusion
of the first obtuse marginal (OM1) branch of the circumflex coronary artery and a
70% occlusion of the left anterior descending (LAD) coronary artery. Operatively,
unusual anatomy was noted; an accessory head was attached superiorly to the
anterior lateral PPM. This gave rise to chordae that were subsequently attached
to the posterior second (P2) scallop. Additionally, the P2 scallop was deficient
in chordae from the posteromedial PPM, thus, loss of this accessory head led to
severe mitral regurgitation. We review the PPM anatomy and pathological context
of PPM rupture and ischaemic mitral regurgitation.
PMID- 28703037
TI - Mental Health in the Workplace.
AB - Mental health disorders can have a serious impact on workers' well-being and job
success.
PMID- 28703039
TI - Growing Concerns With Workplace Incivility.
AB - Workplace incivility (WPI) is a growing issue across all public and private
sectors. Occupational and environmental health nurses can educate employees and
management about WPI, its risk factors and characteristics, and ways to reduce
incidents of WPI.
PMID- 28703038
TI - Rehabilitation Interventions to modify endocrine-metabolic disease risk in
Individuals with chronic Spinal cord injury living in the Community (RIISC): A
systematic review and scoping perspective.
AB - CONTEXT: Endocrine-metabolic disease (EMD) risk following spinal cord injury
(SCI) is associated with significant multi-morbidity (i.e. fracture, diabetes,
heart disease), mortality, and economic burden. It is unclear to what extent
rehabilitation interventions can modify EMD risk and improve health status in
community-dwelling adults with chronic SCI. OBJECTIVES: To characterize
rehabilitation interventions and summarize evidence on their
efficacy/effectiveness to modify precursors to EMD risk in community-dwelling
adults with chronic SCI. METHODS: Systematic searches of MEDLINE PubMed, EMBASE
Ovid, CINAHL, CDSR, and PsychInfo were completed. All randomized, quasi
experimental, and prospective controlled trials comparing
rehabilitation/therapeutic interventions with control/placebo interventions in
adults with chronic SCI were eligible. Two authors independently selected studies
and abstracted data. Mean differences of change from baseline were reported for
EMD risk outcomes. The GRADE approach was used to rate the quality of evidence.
RESULTS: Of 489 articles identified, 16 articles (11 studies; n=396) were
eligible for inclusion. No studies assessed the effects of rehabilitation
interventions on incident fragility fractures, heart disease, and/or diabetes.
Individual studies reported that exercise and/or nutrition interventions could
improve anthropometric indices, body composition/adiposity, and biomarkers.
However, there were also reports of non-statistically significant between-group
differences. CONCLUSIONS: There was very low-quality evidence that rehabilitation
interventions can improve precursors to EMD risk in community-dwelling adults
with chronic SCI. The small number of studies, imprecise estimates, and
inconsistency across studies limited our ability to make conclusions. A high
quality longitudinal intervention trial is needed to inform community-based
rehabilitation strategies for EMD risk after chronic SCI.
PMID- 28703040
TI - Metformin: Adjunct Therapy in Cancer Treatment.
AB - An employee undergoing cancer treatment was prescribed metformin, a medication
used in the treatment of type 2 diabetes and currently used as adjunct therapy
for cancer. Metformin's anti-inflammatory properties inhibit tumor growth. It is
speculated that cancer cells develop a metabolism that enhances aerobic
glycolysis, which promotes cell growth and increases the need for glucose.
Metformin decreases insulin in the blood, which decreases the amount of glucose
available to cancer cells, thus starving the cells of nutrition, resulting in
cell death. This case study explores the role of metformin in cancer treatment,
with implications for occupational health nurses.
PMID- 28703041
TI - A Review of Control Options and Externalities for Verticillium Wilts.
AB - Plant pathogens migrate to new regions through human activities such as trade,
where they may establish themselves and cause disease on agriculturally important
crops. Verticillium wilt of lettuce, caused by Verticillium dahliae, is a
soilborne fungus that was introduced to coastal California via infested spinach
seeds. It has caused significant losses for lettuce growers. Once introduced,
Verticillium wilt could be managed by fumigating with methyl bromide and
chloropicrin, but this option is no longer available. Growers can also manage the
disease by planting broccoli or not planting spinach. These control options
require long-term investments for future gain. Verticillium wilt can also be
prevented or controlled by testing and providing spinach seeds with little or no
V. dahliae infestation. However, seed companies have been reluctant to test or
clean spinach seeds, as spinach crops are not affected by Verticillium wilt.
Thus, available control options are affected by externalities. Renters and other
producers with short time horizons will not undertake long-term investments and
seed companies do not take into account the effect of their decision not to test
on lettuce producers. We review the literature on the economics of managing crop
disease; discuss the economics of managing Verticillium wilt; and review the
recent research on the externalities that arise with short-term growers, and
between seed companies and growers due to Verticillium wilt. An externality
arises whenever the actions of one individual or firm affects the payoffs to
another individual or firm not involved in a specific transaction. These
externalities have important implications for the management of Verticillium wilt
and, more broadly, for the management of migratory pathogens and the diseases
they cause in agriculture in general. This review is of interest to policy
makers, the producers, marketers, seed companies, and researchers.
PMID- 28703042
TI - Genome-Wide Association Mapping of Fusarium Head Blight Resistance in Spring
Wheat Lines Developed in the Pacific Northwest and CIMMYT.
AB - Fusarium head blight (FHB) is a destructive disease of wheat in humid and
semihumid areas of the world. It has emerged in the Pacific Northwest (PNW) in
recent years because of changing climate and crop rotation practices. Our
objectives in the present study were to identify and characterize quantitative
trait loci (QTL) associated with FHB resistance in spring wheat lines developed
in the PNW and the International Maize and Wheat Improvement Center. In total,
170 spring wheat lines were evaluated in field and greenhouse trials in 2015 and
2016. Fourteen lines showing consistent resistance in multiple environments were
identified. These lines are valuable resources in wheat variety improvement of
FHB resistance because they have no Sumai 3 or Sumai 3-related background. The
170 lines were genotyped using a high-density Illumina 90K single-nucleotide
polymorphisms (SNP) assay and 10 other non-SNP markers. A genome-wide association
analysis was conducted with a mixed model (Q+K). Consistent, significant SNP
associations with multiple traits were found on chromosomes 1B, 2B, 4B, 5A, 5B,
and 6A. The locus on chromosome 5B for reduced deoxynivalenol content may be
novel. The identified QTL are being validated in additional mapping studies and
the identified resistant lines are being used in variety development for FHB
resistance and facilitated by marker-assisted selection.
PMID- 28703043
TI - Acid-sensitive lipidated doxorubicin prodrug entrapped in nanoemulsion impairs
lung tumor metastasis in a breast cancer model.
AB - AIM: To develop an acid-sensitive lipidated, doxorubicin (Dox) prodrug (C16-Dox)
to be entrapped in lipid nanoemulsion (NE-C16-Dox) as a nanocarrier to treat
breast cancer models (in vitro and in vivo). RESULTS: We report the efficacy of
NE-C16-Dox in in vitro experiments, as well as the improved chemotherapeutic
index and tumor-control efficacy compared with treatment with free Dox in an in
vivo murine 4T1 breast cancer model. In addition, NE-C16-Dox allowed the use of a
higher dose of Dox, acceptable biocompatibility and a significant reduction in
lung metastasis. CONCLUSION: Taken together, these results indicate that NE-C16
Dox is promising for breast cancer treatment, thus creating possibilities to
translate these nanotechnology concepts to clinical applications.
PMID- 28703044
TI - Implementation of a Safe Patient Handling Program in a Multihospital Health
System From Inception to Sustainability: Successes Over 8 Years and Ongoing
Challenges.
AB - Musculoskeletal injuries, especially back injuries, are among the most frequent
injuries sustained by direct caregivers who lift, transfer, and reposition
patients. These injuries can be debilitating and, for some caregivers, career
ending. In the first year following implementation of the safe patient handling
program in a multihospital health care system, an 82% reduction in Occupational
Health and Safety Administration (OSHA) recordable patient handling injuries was
realized, a 94% decrease in days away from work, an 85% reduction in restricted
duty days, and an 82% reduction in incurred workers' compensation costs. These
reductions have been sustained for an 8-year period since the program's
implementation in 2008. The primary focus of the program's first year was
training and education. Compliance and retraining efforts began in the second
year, followed by a gradual transition to the present emphasis on sustainability.
This article describes the development and implementation of a safe patient
handling program in a multihospital health system and the impact on caregiver
injuries over 8 years. Also presented are key strategies that were used to
achieve sustainability.
PMID- 28703045
TI - The role of human host genetics in tuberculosis resistance.
AB - INTRODUCTION: Tuberculosis (TB) remains a public health problem: the latest
estimate of new incident cases per year is a staggering 10.4 million. Despite
this overwhelming number, the majority of the immunocompetent population can
control infection with Mycobacterium tuberculosis. The human genome underlies the
immune response and contributes to the outcome of TB infection. Areas covered:
Investigations of TB resistance in the general population have closely mirrored
those of other infectious diseases and initially involved epidemiological
observations. Linkage and association studies, including studies of VDR, SLC11A1
and HLA-DRB1 followed. Genome-wide association studies of common variants, not
necessarily sufficient for disease, became possible after technological
advancements. Other approaches involved the identification of those individuals
with rare disease-causing mutations that strongly predispose to TB, epistasis and
the role of ethnicity in disease. Despite these efforts, infection outcome, on an
individual basis, cannot yet be predicted. Expert commentary: The early
identification of future disease progressors is necessary to stem the TB
epidemic. Human genetics may contribute to this endeavour and could in future
suggest pathways to target for disease prevention. This will however require
concerted efforts to establish large, well-phenotyped cohorts from different
ethnicities, improved genomic resources and a better understanding of the human
genome architecture.
PMID- 28703046
TI - Multivessel versus culprit lesion only percutaneous coronary intervention in
cardiogenic shock complicating acute myocardial infarction: A systematic review
and meta-analysis.
AB - BACKGROUND: Early revascularisation of the culprit lesion is the therapeutic
cornerstone in cardiogenic shock complicating acute myocardial infarction. The
optimal management of additional non-culprit lesions is unclear. This systematic
review and meta-analysis aims to summarise current evidence on the comparison of
immediate multivessel percutaneous coronary intervention (MV-PCI) or culprit
lesion only PCI with possible staged revascularisation (C-PCI) in patients with
cardiogenic shock complicating acute myocardial infarction. METHODS: Medical
literature databases were screened to identify analyses comparing MV-PCI with C
PCI in patients with cardiogenic shock complicating acute myocardial infarction
and multivessel coronary artery disease. In absence of randomised trials, 10
cohort studies were included in the current meta-analysis. The primary outcome of
short-term mortality was assessed at hospital discharge or 30 days after hospital
admission. Secondary outcomes were long-term mortality as well as myocardial re
infarction, stroke, acute renal failure, and bleeding at short-term follow-up.
RESULTS: Of 6051 patients, 1194 (19.7%) received MV-PCI and 4857 (80.3%) C-PCI.
Short-term mortality was 37.5% in patients undergoing MV-PCI compared with 28.8%
in C-PCI patients (risk ratio 1.26, 95% confidence interval 1.12-1.41, p=0.001).
Long-term mortality ( p=0.77), myocardial re-infarction ( p=0.77), stroke (
p=0.12), acute renal failure ( p=0.17) and bleeding ( p=0.53) did not differ
significantly between the two revascularisation groups. CONCLUSIONS: Results of
this first meta-analysis on the interventional management of patients with
cardiogenic shock complicating acute myocardial infarction and multivessel
coronary artery disease do not support MV-PCI over C-PCI. However, possible
treatment selection bias in the individual studies must be taken into account.
PMID- 28703047
TI - Assessment of people who have been tasered.
AB - The use of Tasers(r) by the police is subject to intense scrutiny and
controversy. With increasing numbers of police officers carrying Tasers, it is
important that nurses in pre-hospital, emergency department and police custody
settings understand how Tasers work, and the physiological effects. This article
describes Tasers, their mechanisms and physiological effects, and explains how
nurses should undertake assessment of people who have been subjected to Taser
discharge.
PMID- 28703049
TI - RAPID Research Methods for Nurses, Midwives and Health Professionals Rees Colin
RAPID Research Methods for Nurses, Midwives and Health Professionals 144pp L19.99
Wiley Blackwell 9781119048411 1119048419 [Formula: see text].
AB - The ability to understand research language is a requisite for nurses in the era
of evidence-based care provision. The user-friendly text provides extremely
accessible information for this purpose.
PMID- 28703048
TI - Signs of domestic abuse.
AB - Essential facts The government's definition of domestic violence and abuse,
published in 2016 by the Home Office, is: 'Any incident or pattern of incidents
of controlling, coercive, threatening behaviour, violence or abuse between those
16 years or over who are, or have been, intimate partners or family members,
regardless of gender or sexuality.'
PMID- 28703050
TI - Addressing the needs of those who care for us.
AB - If we view our lives as a series of experiences over time, some years will appear
more significant than others. I will remember 2016, for example, as a year of
celebrity death - of loss to our culture rather than to me personally.
PMID- 28703051
TI - Advanced practitioners in emergency care: a literature review.
AB - There has been an expansion of advanced practitioner roles, such as advanced
clinical practitioners, in emergency departments (EDs) in recent years, with the
assumption that they will positively affect the provision and quality of
emergency care. This article presents a literature review which aimed to identify
the evidence on the effects of advanced practitioners in emergency care. The
search revealed only four papers, but these studies did identify a need for the
role, and highlighted positive attitudes towards it and its potential to improve
patient care. The studies also raised concerns about the lack of clarity about
titles, education, skills and competence, issues that must be addressed before
implementation of such roles. There is clearly an urgent need for further
research, but with careful consideration and implementation, advanced clinical
practitioners, like the established emergency nurse practitioner role, can
positively affect emergency care provision and help address the challenges faced
by EDs across the UK.
PMID- 28703052
TI - Launching Your Career in Nursing and Midwifery:A Practical Guide Smoker Annabel
Launching Your Career in Nursing and Midwifery:A Practical Guide 192pp L13.99
Palgrave Macmillan Education 9781137362407 1137362405 [Formula: see text].
AB - This is a useful guide to help students prepare for the application and interview
process associated with their first nursing or midwifery post.
PMID- 28703053
TI - Every child with an autism spectrum condition has specific needs.
AB - Autism is a lifelong developmental disability that affects perceptions of the
world and interactions with other people. About 700,000 people, or one in 100,
live with an autism spectrum condition (ASC) in the UK and there is greater
prevalence among males.
PMID- 28703055
TI - From twitter.
AB - Nurses on Twitter.
PMID- 28703054
TI - Investing in the future of young people.
AB - Atrocious events seem to have multiplied in frequency recently. Sometimes it
feels as if we have become almost inured to their obscenity. No sooner has the
impact and aftermath of one event receded into the past than along comes another
to test our reserves.
PMID- 28703056
TI - NHS to review safety procedures in buildings.
AB - The NHS has confirmed it is reviewing procedures in the wake of the devastating
Grenfell Tower fire in London, as concerns were raised about fire safety in
hospital buildings.
PMID- 28703057
TI - DonorPath NHS Blood and Transplant Free to teams.
AB - DonorPath has been launched to assist specialist nurses who work in organ
donation.
PMID- 28703059
TI - Call for nurses to share experiences.
AB - Former emergency nurse and whistleblower Helene Donnelly, who brought more than
100 incidents to light while working at Stafford Hospital, has said it is 'vital'
nurses share their experiences of raising concerns.
PMID- 28703061
TI - Appeal launched as rate of sickle cell disease rises.
AB - More people from the African-Caribbean community are needed to donate blood due
to growing rates of sickle cell disease.
PMID- 28703062
TI - New thinking needed for emergency services.
AB - Recent events in London and Manchester have highlighted the difficult and
challenging role played by the emergency services. Their swift and professional
response has drawn universal praise, but also raised concerns about reduced
funding levels and job cuts against a heightened security threat.
Transformational reforms are needed to improve our emergency services in a time
of austerity.
PMID- 28703063
TI - Caring for children with autism spectrum condition in paediatric emergency
departments.
AB - The needs of children with autism spectrum condition (ASC) in paediatric
emergency departments (EDs) can often be overlooked. EDs are high-stress
environments for children with ASC, which can result in meltdowns, making the
diagnostic process challenging. There should be provision for children with ASC,
who can have sensory, behavioural and communication needs, in the same way that
analgesia is provided for children in pain. This article promotes a multi
strategy approach to making reasonable adjustments to help meet the needs of
these children and provide them with a positive hospital experience.
PMID- 28703066
TI - Cardiopulmonary resuscitation on a moving boat.
AB - A study has found that surf lifeguards can deliver good-quality cardiopulmonary
resuscitation (CPR) on moving inflatable rescue boats, but that it is less
effective than when delivered onshore.
PMID- 28703064
TI - Guidance on oxygen use in adults.
AB - Essential facts Oxygen is one of the most commonly used drugs in emergency
medicine and before publication of the first British Thoracic Society (BTS) 2008
guideline, emergency departments and ambulance services gave oxygen to almost all
breathless or seriously ill patients.
PMID- 28703068
TI - New competency framework for emergency nurses.
AB - A competency framework for emergency nurses and those wanting a career in the
role has been launched in an effort to aid recruitment and retention.
PMID- 28703069
TI - Training plan makes most of budget.
AB - A nurse-led collaboration between emergency departments (EDs) across south east
England is allowing staff greater access to training and sharing best practice.
PMID- 28703070
TI - When disaster strikes: how the emergency services provide a rapid response.
AB - As the major trauma centre for north west London, St Mary's Hospital cared for
casualties from the two terrorist attacks in the capital - in Westminster and
Borough Market - as well as victims of the fire at Grenfell Tower (pictured).
PMID- 28703071
TI - Reporting occupational violence in emergency departments.
AB - A study has revealed that emergency department (ED) staff across all roles
receive verbal abuse from patients, but that nurses are more likely to be
physically assaulted and are less likely to feel safe.
PMID- 28703072
TI - 'It's up to nurses to tell politicians how it is'.
AB - What is your job? I am a practising advanced nurse practitioner in urgent first
contact care and visiting professor of prescribing and medicines at Birmingham
City University. I also have roles with the Resuscitation Council UK and the
British National Formulary. As an independent consultant, I work with
organisations to investigate errors, as well as chairing and presenting
conferences.
PMID- 28703073
TI - Persistence of immune responses to vaccine against haemorrhagic fever with renal
syndrome in healthy adults aged 16-60 years: results from an open-label2-year
follow-up study.
AB - BACKGROUND: Approximately 2 million doses of vaccine against haemorrhagic fever
with renal syndrome (HFRS) have been used annually in China. However, there were
limited studies focused on persistence of immune responses to HFRS vaccine in
healthy adults. A phase 4, multicentre, open trial has been undertaken to assess
antibody persistence after HFRS vaccination of healthy adolescents and adults
aged 16-60 years. METHODS: The vaccine was administered as a three-dose series at
0, 2 weeks and 6 months, including two primary doses and one booster dose. Anti
hantavirus IgG antibodies were measured by enzyme-linked immunosorbent test
(ELISA) pre-vaccination and 1.5, 7 and 24 months after the initial vaccination.
RESULTS: A total of 143 individuals aged 16-60 years were included. The median OD
(range) values of IgG antibody were 0.005 (0.004-0.016), 0.116 (0.036-0.620),
0.320 (0.065-0.848) and 0.128 (0.011-0.649) pre-vaccination and at 1 month after
the two primary doses, 1 month after the booster dose and 18 months after the
booster dose. The positivity rate was 7.7%, 40.6%, 62.2% and 48.2%, respectively.
CONCLUSIONS: The two primary doses could help healthy individuals to generate an
immune response, and this three-dose series may be better than a two-dose
regimen.
PMID- 28703074
TI - Serum ionic dysequilibria in clinical opioid dependence: Cross-sectional and
longitudinal studies.
AB - INTRODUCTION: Despite an increasing awareness that the activity of excitable
membranes is determined by the underlying ionic gradients across them, and their
importance in drug dependency, we were not able to identify any reports of
comparing the electrolyte composition of opioid-dependent and non-addicted
controls. METHODS: Linear regression was used to compare clinical pathology blood
results taken from 2699 opioid-dependent patients (ODP) and 5307 medical control
(MC) patients on a total of 21,734 occasions for the period 1995-2015. The
presence of a hepatitis C antibody test was used to separate OPD and MC patients.
RESULTS: The mean age among ODP and MC was 33.51 +/- 0.16 and 37.99 +/- 0.23
years, respectively ( p < 0.0001). The groups were 71.5% and 54.2% male ( p <
0.0001). Drug use in this cohort has been reported previously. Analysis of
sodium, haemoglobin and albumin were used to exclude marked effects of
haemodilution/haemoconcentration. Repeated measures linear regression against age
and time showed depressed levels of bicarbonate ( p < 0.0001) and potassium ( p <
0.05) and elevated levels of chloride ( p < 0.025) and anions ( p < 0.01) in ODP
in both sexes. Multiple regression in mixed-effects models showed that these
effects were all worse in females ( p = 0.0001). CONCLUSION: This data shows that
opioid dependence is associated with significant changes in chloride, potassium,
bicarbonate and anions in both sexes, and worse in females. This likely has
implications for the electrophysiological properties of excitable membranes. It
is consistent with the reported impairment of potassium-chloride exchangers in
opioid dependence. Explication of the mechanisms responsible must await further
studies.
PMID- 28703075
TI - Using Dextran-encapsulated gold nanoparticles as insulin carriers to prolong
insulin activity.
AB - AIM: Diabetes mellitus is commonly treated with painful insulin injections. We
aim to explore drug carriers that can prolong insulin activity. MATERIALS &
METHODS: Dextran-encapsulated gold NPs (AuNPs@Dextran) that can bind with insulin
are used as insulin carriers. The affinity (K d = ~42 pM) between insulin and
insulin receptors on the cells is much higher than that (K d = ~4.02 MUM) of
insulin and AuNPs@Dextran. Thus, insulin released from the AuNP@Dextran-insulin
conjugates to maintain kinetic equilibrium and prefers to bind to the insulin
receptor. The slow release of insulin from the AuNP@Dextran-insulin conjugates
facilitates the lasting of insulin activity. RESULTS & DISCUSSION: AuNP@Dextran
insulin conjugates can prolong insulin activity to 12 h, whereas free form
insulin loses activity after 4 h in adipocyte cells. CONCLUSION: AuNPs@Dextran
are suitable carriers that can prolong insulin activity.
PMID- 28703076
TI - Sampling, characterisation and processing of solid recovered fuel production from
municipal solid waste: An Italian plant case study.
AB - This article presents the classification of solid recovered fuel from the
Massafra municipal solid waste treatment plant in Southern Italy in compliancy
with the EN 15359 standard. In order to ensure the reproducibility of this study,
the characterisation methods of waste input and output flow, the mechanical
biological treatment line scheme and its main parameters for each stage of the
processing chain are presented in details, together with the research results in
terms of mass balance and derived fuel properties. Under this study, only 31% of
refused municipal solid waste input stream from mechanical biological line was
recovered as solid recovered fuel with a net heating value (NC=HV) average of
15.77 MJ kg-1; chlorine content average of 0.06% on a dry basis; median of
mercury <0.0064 mg MJ-1 and 80th percentile <0.0068 mg MJ-1. The solid recovered
fuel produced meets the European Union standard requirements and can be
classified with the class code: Net heating value (3); chlorine (1); mercury (1).
PMID- 28703077
TI - Acute myeloid leukemia during pregnancy: a systematic review and meta-analysis.
AB - Data regarding clinical characteristics, therapy, maternal and fetal outcomes of
pregnancy-associated acute myeloid leukemia (PA-AML) are limited. This study
(including 138 cases published between 1955 and 2013) provides comprehensive
assessment of these clinical parameters and may serve as a platform for
developing management recommendations. Most patients (58%) received anthracycline
cytarabine-based regimens (ACBRs), which were associated with significantly
increased complete remission (CR: 91%). Yet, the maternal overall survival (OS:
~30%) was relatively low, probably reflecting reduced application of risk-adapted
consolidation and allogeneic stem cell transplantation (allo-SCT). Fetal exposure
to ACBRs resulted in a live birth rate of 87%, with complications (16%) diagnosed
only in chemotherapy-subjected neonates. This study demonstrates safety and
efficacy of ACBRs during pregnancy. Therapy and delivery schedule should allow
early referral of high-risk patients to allo-SCT. Generation of a pool of high
quality data on PA-AML could contribute to providing evidence-based therapy and
lead to improved maternal and fetal survival.
PMID- 28703078
TI - Chrysophanol suppresses pro-inflammatory response in microglia via regulation of
Drp1-dependent mitochondrial fission.
AB - OBJECTIVES: Chrysophanol, also called chrysophanic acid, is a natural
anthraquinone compound found in Rheum palmatum. R. palmatum has been used in
oriental medicine in ancient East Asia. Microglial cells represent not only the
forefront immune defense in the central nervous system but also the most reactive
sensors to various threats. However, activated microglia can exert neurotoxic
effects via excessive production of cytotoxic molecules and proinflammatory
cytokines. Therefore, modulation of microglial cell activation is important for
maintaining neuronal function. MATERIALS AND METHODS: Pretreatment of
chrysophanol in BV-2 murein microglial cells was carried out for 1 hour, followed
by stimulation with 1 MUg/mL LPS. Level of proteins and RNAs were detected by
western blotting and Reverse Transcriptase PCR. DsRed2-Mito-expressing cells were
used for detecting mitochondrial morphology. RESULTS: In this study, we
determined the effects of chrysophanol on lipopolysaccharide (LPS)-induced
microglial activation. Chrysophanol inhibited the LPS-induced production of
proinflammatory mediators and cytokines via suppression of mitogen-activated
protein kinase/nuclear factor kappa-B activation and reactive oxygen species
generation. In addition, chrysophanol downregulated LPS-induced mitochondrial
fission by diminishing dynamin-related protein 1 (Drp1) dephosphorylation. Taken
together, chrysophanol suppressed the proinflammatory response of activated
microglia via inhibition of Drp1-dependent mitochondrial fission. CONCLUSION: Our
findings can provide the basis for the use of chrysophanol in microglial
inflammatory response-mediated neurodegenerative diseases. Furthermore, our study
can contribute to the production of new drugs for inflammatory response-mediated
neurodegenerative diseases by purification of chrysophanol.
PMID- 28703079
TI - Insights into neuro-urology.
PMID- 28703080
TI - Editorial: Novel Interventional Targets for Gastrointestinal and Metabolic
Disorders.
PMID- 28703081
TI - Editorial: Review on Intracerebral Haemorrhage: Multidisciplinary Approaches to
the Injury Mechanism Analysis and Therapeutic Strategies.
PMID- 28703082
TI - Dental injuries in younger emergency department patients.
AB - BACKGROUND: Dental trauma is a relatively common occurrence in childhood, with an
impact exceeding that of periodontal diseases. It places a significant burden on
the public health system because of its high frequency, impact on quality of life
and consumption of resources. OBJECTIVES: To identify changing trends of dental
injury in patients between 0-18 years of age in Canada and provide a detailed
assessment of dental injury patterns in patients attending a large pediatric
tertiary care hospital. METHODS: This retrospective study was carried out in two
parts. Firstly, data from patients who presented to the emergency departments of
the 15 Canadian hospitals involved in the Injury Reporting and Prevention Program
(CHIRPP) from 1st January 1990 to 31st December 2013 was collected. Secondly, at
the Hospital for Sick Children, charts of patients identified from the
aforementioned database from the years 2008, 2012 and 2015 were accessed for
additional clinical data. RESULTS: Based on CHIRPP data there appears to be an
increasing incidence in dental injuries presenting to emergency departments
nationally. Participation in sports and cycling contributed to the majority of
dental injuries. The use of safety equipment such as helmets with a face-grill
and mouth-guard was low. CONCLUSIONS: Our study demonstrates a rising incidence
of dental injuries in young patients. Most dental injuries occurred during sports
and playground related activities. The low rate of use of safety equipment and
playground safety measures suggests that Canadian Standards Association standards
for playgrounds could be more effective if strengthened by mandatory legislation.
PMID- 28703083
TI - Explaining use of food parenting practices: the importance of predisposing
factors and parental cognitions.
AB - OBJECTIVE: The high energy intake from energy-dense foods among children in
developed countries is undesirable. Improving food parenting practices has the
potential to lower snack intakes among children. To inform the development of
interventions, we aimed to predict food parenting practice patterns around
snacking (i.e. 'high covert control and rewarding', 'low covert control and non
rewarding', 'high involvement and supportive' and 'low involvement and
indulgent'). DESIGN: A cross-sectional survey was conducted. To predict the
patterns of food parenting practices, multinomial logistic regression analyses
were run with 888 parents. Predictors included predisposing factors (i.e.
parents' and children's demographics and BMI, parents' personality, general
parenting, and parenting practices used by their own parents) and parents'
cognitions (i.e. perceived behaviour of other parents, subjective norms,
attitudes, self-efficacy and outcome expectations). SETTING: The Netherlands
(October-November 2014). SUBJECTS: Dutch parents of children aged 4-12 years old.
RESULTS: After backward elimination, nineteen factors had a statistically
significant contribution to the model (Nagelkerke R 2=0.63). Overall, self
efficacy and outcome expectations were among the strongest explanatory factors.
Considering the predisposing factors only, the general parenting factor
nurturance most strongly predicted the food parenting clusters. Nurturance
particularly distinguished highly involved parents from parents employing a
pattern of low involvement. CONCLUSIONS: Parental cognitions and nurturance are
important factors to explain the use of food parenting practices around snacking.
The results suggest that intervention developers should attempt to increase self
efficacy and educate parents about what constitute effective and ineffective
parenting practices. Promoting nurturance might be a prerequisite to achieve
prolonged change.
PMID- 28703084
TI - CASE STUDY ON AN IPILIMUMAB COST-CONTAINMENT STRATEGY IN AN ITALIAN HOSPITAL.
AB - OBJECTIVES: Ipilimumab is the first licensed immune checkpoint inhibitor for
treatment of melanoma. The promising results of the registration clinical study
need confirmation in real practice and its clinical success comes together with a
relevant budget impact due to the high price of this drug. The aim of this work
is to describe a new model of economical sustainability of ipilimumab developed
in an Italian reference center for melanoma treatment. METHODS: This
retrospective, observational, and monocentric study was carried out at the Veneto
Institute of Oncology. Ipilimumab was administered to fifty-seven patients with
advanced melanoma. Overall survival, progression free survival, and toxicity were
evaluated. A local management procedure was evaluated together with the cost
saving strategies implemented by the Italian Medicines Agency (AIFA). RESULTS: We
demonstrated that the use of ipilimumab for metastatic melanoma in real practice
had an efficacy and toxicity similar to that reported in the literature. In this
scenario, our management model (centralization of compounding + drug-day)
permitted savings up to the 11.1 percent of the gross cost for the drug
(calculated assuming that no cost saving procedures were applied) while the
policy of cost containment designed by AIFA produced an additional 6.2 percent of
savings. CONCLUSIONS: In real practice conditions, the centralized administration
of ipilimumab allows to replicate the results of clinical studies and in the
meantime to contain the cost associated with this drug. The local strategy of
management can be readily applied to most of the high cost drugs compounded in
the hospital pharmacy. Impact of findings on practice: (i) We describe a new
model of economic sustainability (drug-day, centralization of compounding,
payback systems) of an expensive and innovative drug, ipilimumab, for treatment
of melanoma within an Italian cancer center. (ii) This pivotal study demonstrated
that a cost containment strategy is feasible and it needs the cooperation of all
healthcare providers (oncologists, pharmacists, nurses, and technicians) to
guarantee the full efficiency of the process.
PMID- 28703085
TI - Contribution of ultra-processed foods in the diet of adults from the French
NutriNet-Sante study.
AB - OBJECTIVE: Concerns have been raised about the potential health impact of ultra
processed foods (UPF) in the diet. Our objective was to investigate the
contribution of UPF in the diet in a large French population and its association
with sociodemographic factors and dietary patterns. DESIGN: Cross-sectional
analysis of dietary data from 74 470 participants in the web-based NutriNet-Sante
cohort. UPF were identified in repeated 24 h records and the proportion (in
weight) of UPF in the total diet (UPFp) was computed for each participant.
Associations of sociodemographic characteristics and UPFp in quartiles were
assessed using multivariate multinomial logistic regression. Food group
consumption and nutrient intakes across quartiles of UPFp were estimated using
linear regression adjusted for sociodemographic factors and energy intake.
SETTING: France. RESULTS: UPF contributed 18.4 % of the foods consumed in weight
and 35.9 % of total energy intake. Higher UPFp consumption was independently
associated with male gender, younger age, lower education, smoking, and
overweight and obesity (all P<0.0001). Participants in the highest UPFp quartile
consumed lower amounts of fruit and vegetables (difference between quartile 4 and
quartile 1 of UPFp, Delta=-180.3 g/d) and higher amounts of sweet products
(Delta=68.5 g/d) and soft drinks (Delta=98.6 g/d; all P<0.0001). They had higher
intakes of energy (Delta=610 kJ/d (145.7 kcal/d)) and added sugar (Delta=17.1
g/d), and lower intakes of fibre (Delta=-4.04 g/d), beta-carotene (Delta=-1019.6
MUg/d) and Ca (Delta=-87.8 mg/d; all P<0.0001). CONCLUSIONS: UPF represent an
important part of the diet in adults from the French general population and are
associated with unbalanced nutritional intakes.
PMID- 28703086
TI - Ultra-processed foods and the limits of product reformulation.
AB - The nutritional reformulation of processed food and beverage products has been
promoted as an important means of addressing the nutritional imbalances in
contemporary dietary patterns. The focus of most reformulation policies is the
reduction in quantities of nutrients-to-limit - Na, free sugars, SFA, trans-fatty
acids and total energy. The present commentary examines the limitations of what
we refer to as 'nutrients-to-limit reformulation' policies and practices,
particularly when applied to ultra-processed foods and drink products. Beyond
these nutrients-to-limit, there are a range of other potentially harmful
processed and industrially produced ingredients used in the production of ultra
processed products that are not usually removed during reformulation. The sources
of nutrients-to-limit in these products may be replaced with other highly
processed ingredients and additives, rather than with whole or minimally
processed foods. Reformulation policies may also legitimise current levels of
consumption of ultra-processed products in high-income countries and increased
levels of consumption in emerging markets in the global South.
PMID- 28703087
TI - DRUG DISINVESTMENT FRAMEWORKS: COMPONENTS, CHALLENGES, AND SOLUTIONS.
AB - OBJECTIVES: Value assessments of marketed drug technologies have been developed
through disinvestment frameworks. Components of these frameworks are varied and
implementation challenges are prevalent. The objective of this systematic
literature review was to describe disinvestment framework process components for
drugs and to report on framework components, challenges, and solutions. METHODS:
A systematic literature search was conducted using the terms: reassessment,
reallocation, reinvestment, disinvestment, delist, decommission or obsolescence
in MEDLINE, EMBASE, NLM PubMed, the Cochrane Library, and CINAHL from January 1,
2000, until November 14, 2015. Additional citations were identified through a
gray literature search of Health Technology Assessment international (HTAi) and
the International Network of Agencies for Health Technology Assessment (INAHTA)
member Web sites and from bibliographies of full-text reviewed manuscripts.
RESULTS: Sixty-three articles underwent full text review and forty were included
in the qualitative analysis. Framework components including disinvestment terms
and definitions, identification and prioritization criteria and methods,
assessment processes, stakeholders and dissemination strategies, challenges, and
solutions were compiled. This review finds that stakeholders lack the political,
administrative, and clinical will to support disinvestment and that there is not
one disinvestment framework that is considered best practice. CONCLUSIONS: Drug
technology disinvestment components and processes vary and challenges are
numerous. Future research should focus on lessening value assessment challenges.
This could include adopting more neutral framework terminology, setting fixed
reassessment timelines, conducting therapeutic reviews, and modifying current
qualitative decision-making assessment frameworks.
PMID- 28703088
TI - Poor blood pressure control in adults with repaired coarctation of the aorta and
hypertension: a register-based study of associated factors.
AB - BACKGROUND: Arterial hypertension is common in adults with repaired coarctation
of the aorta, and is associated with several severe complications. Aims This
study aimed to investigate the prevalence of poorly controlled (?140/90 mmHg)
blood pressure among patients with diagnosed hypertension and to identify
associated factors. METHODS: In the national register for CHD, adults with
repaired coarctation of the aorta and diagnosed hypertension - defined as a
registry diagnosis and/or use of anti-hypertensive prescription medication - were
identified. Logistic regression analysis was used to identify variables
associated with poorly controlled blood pressure. RESULTS: Of the 243 included
patients, 27.2% were female, the mean age was 45.4+/-15.3 years, and 52.3% had
poorly controlled blood pressure at the last registration. In a multivariable
model, age (years) (OR 1.03, CI 1.01-1.06, p=0.008) was independently associated
with poorly controlled blood pressure and so was systolic arm-leg blood pressure
gradient in the ranges [10, 20] mmHg (OR 4.92, CI 1.76-13.79, p=0.002) to >20
mmHg (OR 9.93, CI 2.99-33.02, p<0.001), in comparison with the reference interval
[0, 10] mmHg. Patients with poorly controlled blood pressure had, on average,
more types of anti-hypertensive medication classes prescribed (1.9 versus 1.5,
p=0.003). CONCLUSIONS: Poorly controlled blood pressure is common among patients
with repaired coarctation of the aorta and diagnosed hypertension, despite what
seems to be more intensive treatment. A systolic arm-leg blood pressure gradient
is associated with poorly controlled blood pressure, even at low levels usually
not considered for intervention, and may be an indicator of hypertension that is
difficult to treat.
PMID- 28703089
TI - A traumatic tale of two cities: a comparison of outcomes for adults with major
trauma who present to differing trauma centres in neighbouring Canadian
provinces.
AB - OBJECTIVES: While the use of formal trauma teams is widely promoted, the
literature is not clear that this structure provides improved outcomes over
emergency physician delivered trauma care. The goal of this investigation was to
examine if a trauma team model with a formalized, specialty-based trauma team,
with specific activation criteria and staff composition, performs differently
than an emergency physician delivered model. Our primary outcome was survival to
discharge or 30 days. METHODS: An observational registry-based study using
aggregate data from both the New Brunswick and Nova Scotia trauma registries was
performed with data from April 1, 2011 to March 31, 2013. Inclusion criteria
included patients 16 years-old and older who had an Injury Severity Score greater
than 12, who suffered a kinetic injury and arrived with signs of life to a level
1 trauma centre. RESULTS: 266 patients from the trauma team model and 111 from
the emergency physician model were compared. No difference was found in the
primary outcome of proportion of survival to discharge or 30 days between the two
systems (0.88, n=266 vs. 0.89, n=111; p=0.8608). CONCLUSIONS: We were unable to
detect any difference in survival between a trauma team and an emergency
physician delivered model.
PMID- 28703090
TI - IMPLEMENTING HEALTH TECHNOLOGY ASSESSMENT-BASED RECOMMENDATIONS IN FINLAND:
MANAGED UPTAKE OF MEDICAL METHODS.
AB - OBJECTIVES: The Managed Uptake of Medical Methods Program (MUMM) started 10 years
ago as a joint venture of the Finnish Office for Health Technology Assessment
(Finohta) and the twenty hospital districts in Finland. The aim is to offer
information on the effectiveness, safety, organizational effects, and costs of
new medical methods to support decisions concerning their uptake in secondary
care. In this article, we discuss the successes and challenges of implementing
the MUMM program. METHODS: A study of awareness and use of five MUMM
recommendations for various medical specialties with short-form web-based surveys
to hospitals. RESULTS: The recommendations were noticed and considered relevant.
In overall assessment they received a mean rating of 8.4 (range: 4 to 10). Two
thirds of the respondents thought MUMM recommendations were useful for practice,
but only a third had actually used them in decision making. CONCLUSIONS: HTA
based MUMM recommendations were well received by physicians but in practice they
are less used than clinical practice guidelines. Short-form electronic surveys
were a useful way of gathering information about awareness and implementation.
The surveys also functioned as another method of informing key physicians about
the recommendations.
PMID- 28703091
TI - Do suicide characteristics differ by age in older people?
AB - : ABSTRACTBackground:Suicide rates increase with age in the population aged over
65 years. The aims of this study were to (i) report the characteristics of older
people who died by suicide; and (ii) investigate whether these characteristics
differ in three age bands: 65-74 years, 75-84 years, and 85+ years. METHODS:
Using information from national coroner records, relevant socio-demographic and
clinical factors in all suicides (age >= 65 years; n = 225) from July 2007 to
December 2012 in New Zealand were analyzed and compared in the three age bands.
RESULTS: We found the older the person, the more likely they are to be widowed
but the less likely to have a past psychiatric admission or recent contact with
psychiatric services in the month prior to suicide. However, most of the older
people (61.7% of 65-74 years, 65.6% of 75-84 years, and 77.3% of 85+ years) had
contact with their general practitioner within one month of suicide. Women were
less likely to use violent methods than men in all three age bands but with
increasing age, men were less likely to use violent methods. CONCLUSIONS: Suicide
characteristics in older people differ by age. The oldest people who die by
suicide are not necessarily under psychiatric services and may benefit from a
primary care-based approach in which there is screening for depression and
suicide risk.
PMID- 28703092
TI - PHARMACEUTICAL BENEFITS ADVISORY COMMITTEE RECOMMENDATIONS IN AUSTRALIA.
AB - OBJECTIVES: The aim of this study was to examine submissions made to the
Pharmaceutical Benefits Advisory Committee (PBAC) and assess whether the
predicted financial impact was associated with a recommendation. The second
objective was to assess whether the financial and utilization estimates for
listing the proposed medicine were reliable. METHODS: Data were extracted from
public summary documents of major submissions considered by the PBAC from 2012 to
2014. Information collected included whether submissions were accepted, rejected,
or deferred; estimated use; and financial impact. For those submissions that were
recommended in 2012 and listed on the Pharmaceutical Benefits Scheme (PBS) by
January 2014, a comparison was made between predicted and actual use and cost in
2014, based on PBS utilization. RESULTS: In 2012 to 2014, the PBAC considered 142
unique major submissions; of those, 65 were recommended for listing. A higher
financial cost to the government was a statistically significant factor in
predicting rejection (p = .004 for cost > AUD 30 million Australian dollars [20.7
million Euros] compared with cost-saving). Of the submissions that were
recommended in 2012 and listed by 2014, the actual use was higher than predicted
for 5/19 medications. The estimated cost was outside the predicted bracket of
cost for 10/19 medications, with 8/19 medications having threefold underestimated
expenditure, and 2/19 items having lower than predicted expenditure. CONCLUSIONS:
This study highlights that the predicted financial impact of a medication to the
PBS budget is associated with a PBAC recommendation and also highlights that
predicted use may not reflect actual prescribing practices.
PMID- 28703093
TI - Cognitive performance norms from the Korean genome and epidemiology study
(KoGES).
AB - BACKGROUND: While normative data on neuropsychological performance provide
baseline metrics for the assessment and diagnosis of mild cognitive impairment
and dementia, a lack of comparative normative data in non-Caucasian populations
makes it difficult to conduct similar evaluations and studies in individuals from
diverse backgrounds. The current paper aims to provide normative data on a range
of cognitive measures in a Korean general population sample and investigate
various demographic and health variables associated with cognitive performance in
this representative population. METHOD(S): The study population was 1,528 stroke
and dementia-free individuals who participated in the Korean Genome and
Epidemiology study (KoGES) (mean age 60.43 +/- 7.30, 52.42% female). All
participants underwent a comprehensive neuropsychological test battery that
included verbal and visual memory, language, attention, and executive function
measures. A health examination and a questionnaire-based interview were also
administered. RESULTS: The majority of cognitive test results were associated
with age, education, and gender. In general, higher education and younger age was
associated with better cognitive performance. Explained variance increased
modestly in models that included measures of general health and depressive
symptoms. CONCLUSION: Normative data of cognitive performance in a community
based Korean population are presented. These norms provide reference values in a
non-Caucasian middle to older aged sample.
PMID- 28703094
TI - Dynamic Headspace Sampling as an Initial Step for Sample Preparation in
Chromatographic Analysis.
AB - This work represents a brief summary of the use of dynamic headspace (DHS) as a
technique for sample preparation in chromatographic analysis. Despite numerous
developments in the area of analyte isolation and enrichment, DHS remains one of
the fundamental methods used with GC. In our opinion, interest in this technique
will not diminish significantly because it conforms to stipulations of green
analytical chemistry. Moreover, DHS fulfills the need for methods that facilitate
detection and determination of analytes present at ultratrace levels in complex
matrixes. The main focus of this work was placed on the theoretical fundamentals
of this method. Also described herein were DHS development, the advantages and
disadvantages of this technique compared with other headspace sampling
techniques, and selected examples of its applications in food and environmental
analyses.
PMID- 28703095
TI - Identification of Microorganisms by Modern Analytical Techniques.
AB - Rapid detection and identification of microorganisms is a challenging and
important aspect in a wide range of fields, from medical to industrial, affecting
human lives. Unfortunately, classical methods of microorganism identification are
based on time-consuming and labor-intensive approaches. Screening techniques
require the rapid and cheap grouping of bacterial isolates; however, modern
bioanalytics demand comprehensive bacterial studies at a molecular level. Modern
approaches for the rapid identification of bacteria use molecular techniques,
such as 16S ribosomal RNA gene sequencing based on polymerase chain reaction or
electromigration, especially capillary zone electrophoresis and capillary
isoelectric focusing. However, there are still several challenges with the
analysis of microbial complexes using electromigration technology, such as
uncontrolled aggregation and/or adhesion to the capillary surface. Thus, an
approach using capillary electrophoresis of microbial aggregates with UV and
matrix-assisted laser desorption ionization time-of-flight MS detection is
presented.
PMID- 28703096
TI - pH-Gradient Liquid Chromatography: Fundamentals and Examples.
AB - In this paper, we acquaint the readers with the fundamentals of gradient
separation, followed by the latest innovations in this field. We describe the
principles of organic modifier- and pH-gradient elution emphasizing the
differences and similarities with isocratic separation. The double organic
modifier-/pH-gradient is also thoroughly reviewed as a useful method for the
simultaneous determination of logkw (substitute of logP) and the pka of analytes
present in complex mixtures.
PMID- 28703097
TI - Legionnaires' disease in Europe, 2011 to 2015.
AB - Under the coordination of the European Centre for Disease Prevention and Control
(ECDC), the European Legionnaires' disease Surveillance Network (ELDSNet)
conducts surveillance of Legionnaires' disease (LD) in Europe. Between 2011 and
2015, 29 countries reported 30,532 LD cases to ECDC (28,188 (92.3%) confirmed and
2,344 (7.7%) probable). Four countries (France, Germany, Italy and Spain)
accounted for 70.3% of all reported cases, although their combined populations
represented only 49.9% of the study population. The age-standardised rate of all
cases increased from 0.97 cases/100,000 population in 2011 to 1.30 cases/100,000
population in 2015, corresponding to an annual average increase of 0.09
cases/100,000 population (95%CI 0.02-0.14; p = 0.02). Demographics and infection
setting remained unchanged with ca 70% of cases being community-acquired and 80%
occurring in people aged 50 years and older. Clinical outcome was known for
23,164 cases, of whom 2,161 (9.3%) died. The overall case fatality ratio
decreased steadily from 10.5% in 2011 to 8.1% in 2015, probably reflecting
improved reporting completeness. Five countries (Austria, Czech Republic,
Germany, Italy, and Norway) had increasing age-standardised LD notification rates
over the 2011-15 period, but there was no increase in notification rates in
countries where the 2011 rate was below 0.5/100,000 population.
PMID- 28703098
TI - Surveillance perspective on Lyme borreliosis across the European Union and
European Economic Area.
AB - Lyme borreliosis (LB) is the most prevalent tick-borne disease in Europe.
Erythema migrans (EM), an early, localised skin rash, is its most common
presentation. Dissemination of the bacteria can lead to more severe
manifestations including skin, neurological, cardiac, musculoskeletal and ocular
manifestations. Comparison of LB incidence rates in the European Union
(EU)/European Economic Area (EEA) and Balkan countries are difficult in the
absence of standardised surveillance and reporting procedures. We explored six
surveillance scenarios for LB surveillance in the EU/EEA, based on the following
key indicators: (i) erythema migrans, (ii) neuroborreliosis, (iii) all human LB
manifestations, (iv) seroprevalence, (v) tick bites, and (vi) infected ticks and
reservoir hosts. In our opinion, neuroborreliosis seems most feasible and useful
as the standard key indicator, being one of the most frequent severe LB
manifestations, with the possibility of a specific case definition. Additional
surveillance with erythema migrans as key indicator would add value to the
surveillance of neuroborreliosis and lead to a more complete picture of LB
epidemiology in the EU/EEA. The other scenarios have less value as a basis for EU
level surveillance, but can be considered periodically and locally, as they could
supply complementary insights.
PMID- 28703099
TI - Letter to the editor: Trends in tuberculosis notification rates by country of
origin in the metropolitan area of Rome, 2010 to 2015.
PMID- 28703101
TI - CT volumetry can potentially predict the local stage for gastric cancer after
chemotherapy.
AB - PURPOSE: We aimed to evaluate the value of CT tumor volumetry for predicting T
and N stages of gastric cancer after chemotherapy, with pathologic results as the
reference standard. METHODS: This study retrospectively evaluated 42 patients
diagnosed with gastric cancer, who underwent chemotherapy followed by surgery.
Pre- and post-treatment CT tumor volumes (VT) were measured in portal venous
phase and volume reduction ratios were calculated. Correlations between pre- and
post-treatment VT, reduction ratio, and pathologic stages were analyzed. Receiver
operator characteristic (ROC) analyses were also performed to assess diagnostic
performance for prediction of downstaging to T0-2 stage and N0 stage. RESULTS:
Pretreatment VT, post-treatment VT, and VT reduction ratio were significantly
correlated with T stage (rs=0.329, rs=0.546, rs= -0.422, respectively). Post
treatment VT and VT reduction ratio were significantly correlated with N stage
(rs=0.442 and rs= -0.376, respectively). Pretreatment VT, post-treatment VT, and
VT reduction ratio were significantly different between T0-2 and T3,4 stage
tumors (P = 0.05, P < 0.001, and P = 0.002, respectively). The differences
between N0 and >=N1 groups were also statistically significant (P = 0.005 for
post-treatment VT, P = 0.016 for VT reduction ratio, respectively). The area
under the ROC curve (AUC) for identification of T0-2 groups was 0.70 for
pretreatment VT, 0.88 for post-treatment VT, and 0.82 for VT reduction ratio,
respectively. AUC was 0.78 for post-treatment VT and 0.74 for VT reduction ratio
for identification of N0 groups. CONCLUSION: CT tumor volumetry, particularly
post-treatment measurement of VT, is potentially valuable for predicting
histopathologic T and N stages after chemotherapy in patients with gastric
cancer.
PMID- 28703102
TI - Intravoxel incoherent motion: application in differentiation of hepatocellular
carcinoma and focal nodular hyperplasia.
AB - PURPOSE: We aimed to explore whether intravoxel incoherent motion (IVIM)-related
parameters of hepatocellular carcinoma (HCC) and focal nodular hyperplasia (FNH)
demonstrate differences that could be used to differentiate and improve
diagnostic efficiency. METHODS: A total of 27 patients, including 22 with HCC and
5 with FNH, underwent liver 3.0 T magnetic resonance imaging for routine
sequences. They were concurrently examined by IVIM diffusion-weighted imaging
(DWI) scanning with 11 different b values (0-800 s/mm2). IVIM-derived parameters,
such as pure diffusion coefficient (D), pseudo-diffusion coefficient (D*),
perfusion fraction (f), and apparent diffusion coefficient (ADCtotal), were
quantified automatically by post-processing software and compared between HCC and
FNH groups. A receiver operating characteristic (ROC) curve was then created to
predict their diagnostic value. RESULTS: D* was weak in terms of reproducibility
among the other parameters. ADCtotal, D, and D* were significantly lower in the
HCC group than in the FNH group, while f did not show a significant difference.
ADCtotal and D had the largest area under the curve values (AUC; 0.915 and 0.897,
respectively) and similarly high efficacy to differentiate the two conditions.
CONCLUSION: IVIM provides a new modality to differentiate the HCC and FNH.
ADCtotal and D demonstrated outstanding and comparable diagnosing utility.
PMID- 28703103
TI - Shining light in a dark landscape: MRI evaluation of unusual localization of
endometriosis.
AB - Endometriosis is a disease distinguished by the presence of endometrial tissue
outside the uterine cavity with intralesional recurrent bleeding and resulting
fibrosis. The most common locations for endometriosis are the ovaries, pelvic
peritoneum, uterosacral ligaments, and torus uterinus. Typical symptoms are
secondary dysmenorrhea and cyclic or chronic pelvic pain. Unusual sites of
endometriosis may be associated with specific symptoms depending on the
localization. Atypical pelvic endometriosis localizations can occur in the
cervix, vagina, round ligaments, ureter, and nerves. Moreover, rare extrapelvic
endometriosis implants can be localized in the upper abdomen, subphrenic fold, or
in the abdominal wall. Magnetic resonance imaging (MRI) represents a problem
solving tool among other imaging modalities. MRI is an advantageous technique,
because of its multiplanarity, high contrast resolution, and lack of ionizing
radiation. Our purpose is to remind the radiologists the possibility of atypical
pelvic and extrapelvic endometriosis localizations and to illustrate the specific
MRI findings. Endometriotic tissue with hemorrhagic content can be distinguished
from adherences and fibrosis on MRI imaging. Radiologists should keep in mind
these atypical localizations in patients with suspected endometriosis, in order
to achieve the diagnosis and to help the clinicians in planning a correct and
complete treatment strategy.
PMID- 28703104
TI - High-pitch dual-source CT angiography without ECG-gating for imaging the whole
aorta: intraindividual comparison with standard pitch single-source technique
without ECG gating.
AB - PURPOSE: We aimed to perform intraindividual comparison of computed tomography
(CT) parameters, image quality, and radiation exposure between standard CT
angiography (CTA) and high-pitch dual source (DS)-CTA, in subjects undergoing
serial CTA of thoracoabdominal aorta. METHODS: Eighteen subjects with
thoracoabdominal CTA by standard technique and high-pitch DS-CTA technique within
6 months of each other were retrieved for intraindividual comparison of image
quality in thoracic and abdominal aorta. Quantitative analysis was performed by
comparison of mean aortic attenuation, noise, signal-to-noise ratio (SNR), and
contrast-to-noise ratio (CNR). Qualitative analysis was performed by visual
assessment of motion artifacts and diagnostic confidence. Radiation exposure was
quantified by effective dose. Image quality was apportioned to radiation exposure
by means of figure of merit. RESULTS: Mean aortic attenuation and noise were
higher in high-pitch DS-CTA of thoracoabdominal aorta, whereas SNR and CNR were
similar in thoracic aorta and significantly lower in high-pitch DS-CTA of
abdominal aorta (P = 0.024 and P = 0.016). High-pitch DS-CTA was significantly
better in the first segment of thoracic aorta. Effective dose was reduced by 72%
in high-pitch DS-CTA. CONCLUSION: High-pitch DS-CTA without electrocardiography
gating is an effective technique for imaging aorta with very low radiation
exposure and with significant reduction of motion artifacts in ascending aorta;
however, the overall quality of high-pitch DS-CTA in abdominal aorta is lower
than standard CTA.
PMID- 28703105
TI - Bronchial artery embolization in hemoptysis: a systematic review.
AB - We systematically reviewed the role of bronchial artery embolization (BAE) in
hemoptysis. Literature search was done for studies on BAE published between 1976
and 2016. Twenty-two studies published in English, with sample size of at least
50 patients, reporting indications, technique, efficacy, and follow-up were
included in the final analysis. Common indications for BAE included tuberculosis
(TB), post-tubercular sequelae, bronchiectasis, and aspergillomas. Most common
embolizing agent used was polyvinyl alcohol (size, 300-600 MUm) with increasing
use of glue in recent years. Overall immediate clinical success rate of BAE,
defined as complete cessation of hemoptysis, varied from 70%-99%. However,
recurrence rate remains high, ranging from 10%-57%, due to incomplete initial
embolization, recanalization of previously embolized arteries, and recruitment of
new collaterals. Presence of nonbronchial systemic collaterals, bronchopulmonary
shunting, aspergillomas, reactivation TB, and multidrug resistant TB were
associated with significantly higher recurrence rates (P < 0.05). Rate of major
complications remained negligible and stable over time with median incidence of
0.1% (0%-6.6%). Despite high hemoptysis recurrence rates, BAE continues to be the
first-line, minimally invasive treatment of hemoptysis in emergency settings,
surgically unfit patients, or in patients with diffuse or bilateral lung disease.
PMID- 28703106
TI - CT perfusion in characterizing anterior mediastinal solid tumors.
PMID- 28703107
TI - Author Reply.
PMID- 28703108
TI - Niepelny, wrodzony zwrot jelita i niezwykle rzadki przypadek niepelnego zwrotu
jelita doroslego chorego z objawami wysokiej niedroznosci przewodu pokarmowego.
AB - Autorzy przedstawiaja 21 -letniego chorego z niepelnym zwrotem jelit z objawami
przewleklej niedroznosci gornego odcinka przewodu pokarmowego i trudnosci
diagnostyczne. Rozstrzygajacym badaniem byla TK jamy brzusznej z kontrastem. Po
operacji sposobem Ladda chory zostal wyleczony.
PMID- 28703109
TI - Comparative Analysis of Immediate Postoperative Complications Following Total
Gastrectomy.
AB - INTRODUCTION: Total gastrectomy (TG), despite disrupting the continuity of the
alimentary tract and accounting for significant postoperative complications, is
the procedure of choice for curative resection of gastric carcinoma. The
objectives of this study were to report the rate of postoperative complications
following TG, to analyze adverse postoperative outcomes, and to determine which
of the two techniques - the Roux-en-Y esophagojejunostomy and Omega-Braun TG, is
safer. MATERIALS AND METHODS: A retrospective, observational study was conducted
among patients diagnosed with gastric carcinoma who underwent TG between January
1st, 2010 and December 31st, 2012 in the Surgery Department of the Bucharest
Clinical Emergency Hospital. Descriptive and analytical statistical analysis with
parametric and non-parametric tests was carried out using GraphPad, with
statistical significance set at p <0.05. RESULTS: Seventy-seven patients, aged 37
91 years (average age 64.1 +/- 11.59 years), were enrolled in this study. A total
of 84 immediate postoperative complications were encountered in 35 patients
(47.5%), classified into local (n=21, 25%) and general complications (n=63, 75%).
Reoperation was necessary in five cases (6.2%), all after Roux-en-Y end-side
esophagojejunostomy. Two deaths (n=2, 2.5%), one after Roux-en-Y and one after
Omega-Braun TG, were reported. DISCUSSION: The Roux-en-Y technique had a higher
number of complications, both local and general. Omega-Braun TG was associated
with a lower number of local complications; however, it was associated with life
threatening complications including hemodynamic instability and multisystem organ
failure. CONCLUSION: The study deemed Roux-en-Y Esophagojejunostomy the overall
safer procedure. A statistically significant correlation between manual
anastomosis and mortality was observed. Total Gastrectomy is a complex procedure
with numerous potential complications which calls for an improved surgical
technique to reduce postoperative risk.
PMID- 28703110
TI - Cell therapy in surgical treatment of fistulas. Preliminary results.
AB - : Risk of recurrence after surgical treatment of a recurrent fistula is up to
50%. It has be known that more aggressive surgical treatment is associated with a
high risk of anal sphincter damage and leads to incontinence. Several studies
have been designed to elaborate minimally invasive treatment of rectovaginal and
anal fistulas. The properties of Adipose-derived Stem Cells (ASC) significantly
enhance a natural healing potency. Here, we present our experience with combined
surgical and cell therapy in the treatment of fistulas. MATERIALS AND METHODS:
Four patients were enrolled in our study after unsuccessful treatments in the
past - patients 1-3 with rectovaginal fistulas including two women after
graciloplasty, and patient 4 - a male with complex perianal fistula. Adipose
tissue was obtained from subcutaneous tissue. ASCs were isolated, cultured up to
10+/-2 mln cells and injected into the walls of fistulas. Follow-up physical
examination and anoscopy were performed at 1, 4, 8, and 12 weeks, 6 and 12 months
after implantation. RESULTS: Up to 8 weeks after ASC implantation, symptoms of
fistulas' tracts disappeared. At 8 weeks, in patients 1-3, communication between
vaginal and rectal openings was closed and at 12-16 w. intestinal continuity was
restored in patient 3 and 4. After a 6-month follow-up, the fistula tract of
patient 4 was closed. Up to 12 m. after ASC implantation no recurrences or
adverse events were observed. CONCLUSION: ASCs combined with surgical pre-treated
fistula tracts were used in four patients. All of them were healed. This
encouraging result needs further trials to evaluate the clinical efficiency and
the cost-effectiveness ratio.
PMID- 28703111
TI - Clinical and microbiological aspects of the use of Lactobacillus rhamnosus PL1
strains in proctological patients with symptoms of chronic proctitis.
AB - : Recurrent proctitis and the symptoms associated therewith pose significant
clinical problem in proctological patients. The objective of this study was to
assess the impact of the probiotic Lactobacillus rhamnosus PL1 strain on the
clinical presentation and composition of intestinal microbiota in patients with
symptoms of proctitis in the course of hemorrhoidal disease and diverticulosis.
Material consisted of 24 patients in whom no complete clinical improvement could
be obtained after the treatment of the underlying disease. Subject to the
assessment was the presence and the intensity of clinical symptoms as well as
qualitative and quantitative changes in the composition of bacterial flora
detected in the stool before, during and after a 9-week supplementation with the
probiotic Lactobacillus rhamnosus PL1 strain. RESULTS: In the entire study group,
the intensity of pain after 12 weeks was significantly lower (p=0,.011) compared
to baseline; the intensity of flatulence and abdominal discomfort was reduced
significantly as early as after 3 weeks, with the difference reaching a highly
significant level after 12 weeks (pP<0,.0001). No significant difference was
observed in the frequency of the reported episodes of diarrhea, constipation, as
well as itching and burning in the anal region. As early as after 3 weeks of
supplementation with the probiotic L. rhamnosus PL1 strain, significant
qualitative and quantitative changes were observed in the composition of
intestinal microbiota; the changes differed depending on the underlying disease.
An increase in the total counts of the bacteria of Lactobacillus genus,
particularly L. rhamnosus PL1 strain was observed regardless of the underlying
disease. CONCLUSION: Tthe probiotic Lactobacillus rhamnosus PL1 strain appears to
be useful in restoring appropriate ratios of bacterial populations in patients
presenting with symptoms of proctitis in the course of the treatment of certain
diseases of the lower gastrointestinal tract.
PMID- 28703112
TI - The usefulness of D-dimer in diagnosis and prediction of venous thromboembolism
in patients with abdominal malignancy.
AB - THE AIM: of the study was to evaluate the usefulness of D-dimer evaluation in the
diagnosis and prediction of venous thromboembolism (VTE) of lower extremities in
patients operated on for abdominal tumors depending on the chosen cut-off point
for this parameter. MATERIAL AND METHODS: We included 150 patients operated on
for abdominal cancer in our department between October 2014 and June 2016. In
these patients, concentration of D-dimer was determined, medical histories were
taken, and physical examinations were performed. Ultrasound exams of the veins of
the lower limbs were performed three times in every patient in order to confirm
or exclude VTE. RESULTS: When a standard cut-off point (500 ng/ml) was used, in
46% of cancer patients D-dimer values were elevated despite the lack of VTE. We
did not detect any influence of cancer stage on the value of D-dimer. However, if
cut-off point was 1440 ng/ml, which has been suggested in the literature, only
14% of patients were false positive. When the upper cut-off value for D-dimer was
raised, the effect of cancer stage on the value of this parameter could be seen.
CONCLUSION: The concentration of D-dimer is often elevated in patients with
active cancer, but is not a sufficient criterion for diagnosis of VTE. The
concentration of D-dimer before surgery does not determine the risk of
postoperative thromboembolic complications. This is undoubtedly related to the
widespread use of effective thromboprophylaxis. According to the literature,
ultrasound is the optimum method for detection of VTE in surgically treated
cancer patients. The effect of cancer stage on the value of D-dimer is revealed
only when the cut-off point in this group is 1440 ng/ml, instead of 500 ng/ml
which is used for the general population.
PMID- 28703113
TI - Role of intraoperative neuromonitoring of the recurrent laryngeal nerves during
thyroid reoperations of recurrent goiter.
AB - : Reoperations of the thyroid gland are challenging to any surgeon. Such
procedures are technically difficult and involve higher risk of complications
than primary procedures. Recurrent laryngeal nerve (RLN) palsy is one of such
complications The aim of the study was to evaluate the effectiveness of
intraoperative neuromonitoring (IONM) in preventing RLN palsy during recurrent
goiter operations. MATERIAL AND METHODS: We retrospectively analyzed the results
of thyroid reoperation performed at the Department of Endocrine, General and
Vascular Surgery of Medical University of Lodz in the period from January 2014 to
June 2016. The study included 80 patients, who were divided into 2 groups: group
A consisted of 27 patients, who had undergone surgery with the use of IONM, while
group B included 53 patients, in whom RLN was identified visually. During
statistical analysis we took into account the number of nerves at risk, not the
number of patients. There were 47 nerves at risk In group A and 86 in group B. We
analyzed whether application of IONM had any effect on the frequency of RLN palsy
and procedure duration. RESULTS: The frequency of RLN palsy was 10.64% (5/47) in
group A and 15.12% (13/86) in group B (no statistical significance, p=0,47). Mean
operation time was shorter in group B 71.29 +/- 17.125 minutes vs. 75.75 +/-
17.94 minutes in group A (no statistical significance, p=0,377). CONCLUSION: Use
of IONM did not significantly reduce the occurrence of RLN palsy and procedure
duration.
PMID- 28703114
TI - Inhibition of PERK-dependent pro-adaptive signaling pathway as a promising
approach for cancer treatment.
AB - : Endoplasmic Reticulum (ER) is an organelle that is vital for cell growth and
maintenance of homeostasis. Recent studies have reported that numerous human
diseases, including cancer, are strictly connected to disruption of ER
homeostasis. In order to counteract adverse intracellular conditions, cancer
cells induce protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK)
dependent, pro-adaptive unfolded protein response (UPR) signaling branches. If ER
stress is severe or prolonged, pro-adaptive signaling networks are insufficient,
resulting in apoptotic cell death of cancer cells. The main aim: of the study was
to evaluate the biological activity of a small-molecule PERK inhibitor GSK2606414
in two cancer cell lines - human neuroblastoma (SH-SY5Y) and human colorectal
adenocarcinoma (HT-29) cell lines. We analyzed the level of phosphorylation of
the eukaryotic initiation factor 2 (eIF2), which is the main substrate of PERK
and a subsequent activator of UPR, which under long-term ER stress may evoke
apoptotic death of cancer cells. MATERIAL AND METHODS: In the study, we utilized
commercially available cell lines of human colorectal adenocarcinoma HT-29 and
human neuroblastoma SH-SY5Y. Cells were exposed to the tested PERK-dependent
signaling inhibitor GSK2606414 in suitable culture media with addition of
thapsigargin (500 nM) to induce ER stress. To identify the protein, Western blot
with specific antibodies was used. Detection of immune complexes was performed
using chemiluminescence. RESULTS: We found a complete inhibition of p-eIF2alpha
expression due to the GSK2606414 inhibitor in both cell lines, SH-SY5Y and HT-29.
CONCLUSIONS: Currently available cancer treatments are insufficient and cause
various side effects. It has been assumed that utilization of small-molecule
inhibitors of the PERK-dependent signaling pathway, like GSK2606414, may switch
the pro-adaptive branch of UPR to its pro-apoptotic branch. It is believed that
the tested inhibitor GSK2606414 may become a promising treatment for many cancer
types.
PMID- 28703115
TI - Incidental diagnosis of the tall-cell variant of the papillary microcarcinoma of
the thyroid gland requires completion lymphadenectomy: case report.
AB - Papillary thyroid carcinoma is the most common neoplasm of the thyroid gland
which is usually associated with a very good prognosis. The aim of this case
report is to present the disease course of a rare tumor of the thyroid gland,
which is worthwhile due to its extraordinary appearance and specific management.
A 46-year-old patient presented with a pronounced right-sided, but bilateral,
multinodular goiter, with a volume of approximately 80 mL, as assessed on
ultrasonography. Surgical removal was indicated as scintigraphy showed a 4-cm
cold nodule that almost completely took up the right thyroid lobe. Because of the
micronodular texture of the left thyroid lobe, complete thyroidectomy was
performed according to well-established guidelines. Histopathological
investigation of the specimen revealed a follicular adenoma without any
malignancy in the right thyroid lobe and the tall-cell variant of the papillary
thyroid microcarcinoma in the left lobe, with a capsular invasion and diameter of
0.6 cm. Because this rare tumor subtype is known for its aggressive behavior, and
there was capsular invasion, low-grade differentiation, and an increased risk for
lymphatic metastases, completion lymphadenectomy of the central compartments was
performed after an interdisciplinary board decision. On histopathology, there
were 30 tumor-free lymph nodes; final TNM classification was as follows: pT3 pN0
[0/30] L0 V0 Pn0 R0). The postoperative course was uneventful, and surgery was
followed by radioiodine therapy. Six months after the surgery, clinical follow-up
did revealed any sign of recurrence. The tall-cell variant is a rare and
aggressive subtype of the papillary thyroid carcinoma, and it is characterized by
poor 5-year survival and high recurrence rate. According to our understanding and
based on current literature, this disease requires an aggressive surgical
treatment and a close follow-up, as recommended by the current guidelines.
PMID- 28703116
TI - Principles of follow-up assessments in patients with breast cancer after radical
treatment.
AB - A follow-up assessment plan after radical treatment is a part of a comprehensive
approach to treating patients with breast cancer. Because breast cancer is the
most frequent cancer both worldwide and in Poland, adequate follow-up is
important not only for patients but also for economic reasons. Herein, we review
current recommendations for follow-up assessments in patients with breast cancer.
The main aim of such assessment is detection of early recurrence or tumor
presence in the other breast, observation of long-term treatment complications,
and creation of multidisciplinary infrastructure that will allow to reduce the
risk of recurrence and alleviate physical, mental, and social consequences of
treatment.
PMID- 28703117
TI - Early diagnostics of temporomandibular joint structural elements injures caused
by traumatic mandibular bone fractures.
AB - A rapidly increasing number of mandibular condylar fractures and some
complications related to injuries of temporomandibular elements make this study
important. Intra-articular disorders lead to secondary pathological findings such
as osteoarthritis, deforming osteoarthrosis, and temporomandibular joint
ankylosis that limits mouth opening, mastication, swallowing, breathing, and
decreased/lost working capacity or disability. Early diagnosis of intra-articular
disorders can prevent from long-lasting functional complications caused by
temporomandibular joint injuries. This study was performed for the purpose of
early detection and investigation of organic pathological changes in the
cartilaginous and osseous tissues of the temporomandibular joint caused by
traumatic fractures of the mandibular condyle. Twenty patients underwent a
general clinical examination, magnetic resonance imaging (MRI), and immune-enzyme
testing for biochemical markers of connective tissue injury (pyridinoline and
deoxypyridinoline) in urine. Disk dislocation, deformation, adhesion, perforation
or squeeze, tension or disruption of ligaments, and injury of articular surfaces
are among complications of mandibular fractures that can be revealed on MRI. As
regards biochemical findings, we revealed a sharp rise in the levels of
pyridinoline and deoxypyridinoline before treatment and a lack of stabilization
within 21 days of treatment.
PMID- 28703118
TI - Cholelithiasis - always infected?
AB - : This study aims to present results regarding the presence and identification of
bacterial strains found in bile and gallstones located in the gallbladder and
bile ducts in patients operated on due to cholelithiasis. MATERIALS AND METHODS:
Bacterial culture was evaluated in 92 patients. There were 54 women (59%) and 38
men (41%) who underwent surgery on account of cholelithiasis and /or gallstones
in bile ducts between 2013 and 2014. Bile and gallstone samples were cultured
intraoperatively for bacteria; bacterial strains were identified, and their
sensitivity to antibiotics was determined. Molecular methods (NGS and Sanger
method) were used to separate bacterial strains in one of the gallbladder stones
and the results were compared with bacterial strains grown from the bile.
RESULTS: Bile cultures were positive in 46 patients that is, 50% of the study
group. The following bacteria strains were grown: Enterococcus spp. (44%),
Escherichia coli (37%) and Klebsiella spp. (35%). Candidiasis accompanied by
bacterial infection was detected in 7 patients (15%). Molecular testing of
gallstones revealed DNA of Enterococcus spp., Escherichia spp., Streptococcus
spp. and Clostridium spp. In the bile culture of the same patient Enterococcus
spp. (avium and faecalis) was detected. Conclusion 1. More than one pathogen was
grown on samples obtained from 31 patients (70%) with bile infection. 2. The most
common pathogens include Enterococcus spp., Escherichia coli and Klebsiella spp.
3. Bacterial infections are often accompanied by a fungal infection (Candida
albicans) 4. Bacterial strains grown from a gallstone sample partially
corresponded with strains identified in the bile of the same patient.
PMID- 28703119
TI - DNA double strand break (DSB) induction and cell survival in iodine-enhanced
computed tomography (CT).
AB - A multi-scale Monte Carlo model is proposed to assess the dosimetric and
biological impact of iodine-based contrast agents commonly used in computed
tomography. As presented, the model integrates the general purpose MCNP6 code
system for larger-scale radiation transport and dose assessment with the Monte
Carlo damage simulation to determine the sub-cellular characteristics and spatial
distribution of initial DNA damage. The repair-misrepair-fixation model is then
used to relate DNA double strand break (DSB) induction to reproductive cell
death. Comparisons of measured and modeled changes in reproductive cell survival
for ultrasoft characteristic k-shell x-rays (0.25-4.55 keV) up to orthovoltage
(200-500 kVp) x-rays indicate that the relative biological effectiveness (RBE)
for DSB induction is within a few percent of the RBE for cell survival. Because
of the very short range of secondary electrons produced by low energy x-ray
interactions with contrast agents, the concentration and subcellular distribution
of iodine within and near cellular targets have a significant impact on the
estimated absorbed dose and number of DSB produced in the cell nucleus. For some
plausible models of the cell-level distribution of contrast agent, the model
predicts an increase in RBE-weighted dose (RWD) for the endpoint of DSB induction
of 1.22-1.40 for a 5-10 mg ml-1 iodine concentration in blood compared to an RWD
increase of 1.07 +/- 0.19 from a recent clinical trial. The modeled RWD of 2.58
+/- 0.03 is also in good agreement with the measured RWD of 2.3 +/- 0.5 for
an iodine concentration of 50 mg ml-1 relative to no iodine. The good agreement
between modeled and measured DSB and cell survival estimates provides some
confidence that the presented model can be used to accurately assess biological
dose for other concentrations of the same or different contrast agents.
PMID- 28703120
TI - Effects of body habitus on internal radiation dose calculations using the 5-year
old anthropomorphic male models.
AB - Computational phantoms are commonly used in internal radiation dosimetry to
assess the amount and distribution pattern of energy deposited in various parts
of the human body from different internal radiation sources. Radiation dose
assessments are commonly performed on predetermined reference computational
phantoms while the argument for individualized patient-specific radiation
dosimetry exists. This study aims to evaluate the influence of body habitus on
internal dosimetry and to quantify the uncertainties in dose estimation
correlated with the use of fixed reference models. The 5-year-old IT'IS male
phantom was modified to match target anthropometric parameters, including body
weight, body height and sitting height/stature ratio (SSR), determined from
reference databases, thus enabling the creation of 125 5-year-old habitus
dependent male phantoms with 10th, 25th, 50th, 75th and 90th percentile body
morphometries. We evaluated the absorbed fractions and the mean absorbed dose to
the target region per unit cumulative activity in the source region (S-values) of
F-18 in 46 source regions for the generated 125 anthropomorphic 5-year-old hybrid
male phantoms using the Monte Carlo N-Particle eXtended general purpose Monte
Carlo transport code and calculated the absorbed dose and effective dose of five
18F-labelled radiotracers for children of various habitus. For most organs, the S
value of F-18 presents stronger statistical correlations with body weight,
standing height and sitting height than BMI and SSR. The self-absorbed fraction
and self-absorbed S-values of F-18 and the absorbed dose and effective dose of
18F-labelled radiotracers present with the strongest statistical correlations
with body weight. For 18F-Amino acids, 18F-Brain receptor substances, 18F-FDG,
18F-L-DOPA and 18F-FBPA, the mean absolute effective dose differences between
phantoms of different habitus and fixed reference models are 11.4%, 11.3%, 10.8%,
13.3% and 11.4%, respectively. Total body weight, standing height and sitting
height have considerable effects on human internal dosimetry. Radiation dose
calculations for individual subjects using the most closely matched habitus
dependent computational phantom should be considered as an alternative to improve
the accuracy of the estimates.
PMID- 28703121
TI - Quasiballistic quantum transport through Ge/Si core/shell nanowires.
AB - We study signatures of ballistic quantum transport of holes through Ge/Si
core/shell nanowires at low temperatures. We observe Fabry-Perot interference
patterns as well as conductance plateaus at integer multiples of 2e 2/h at zero
magnetic field. Magnetic field evolution of these plateaus reveals relatively
large effective Lande g-factors. Ballistic effects are observed in nanowires with
silicon shell thickness of 1-3 nm, but not in bare germanium wires. These
findings inform the future development of spin and topological quantum devices
which rely on ballistic sub-band-resolved transport.
PMID- 28703122
TI - Synergistic effect of electrical conductivity and biomolecules on human meniscal
cell attachment, growth, and proliferation in poly-epsilon-caprolactone
nanocomposite scaffolds.
AB - Poly-epsilon-caprolactone (PCL)-based nanocomposite scaffolds with different
concentrations of carbon nanofillers (carbon nanofibers (CNFs), nanographite, and
exfoliated graphite) have been studied to investigate the effect of electrical
conductivity and biomolecule supplementation for enhanced human meniscal cell
attachment, growth, and proliferation. The incorporation of carbon nanofillers
was found to improve the mechanical and electrical properties. CNF-based
nanocomposite scaffolds showed the highest electrical conductivity with
significant improvements in mechanical properties (more than 50% tensile strength
increase than PCL with 10% (w/w) CNF). All nanocomposite scaffolds were subjected
to cytotoxicity studies using primary meniscus cells. The nanocomposite scaffolds
showing higher cell viability were selected and tested for meniscal cell
attachment and proliferation assays such as total deoxyribonucleic acid content,
extracellular matrix secretion, nuclear staining, and cell attachment studies
using a scanning electron microscope. When an optimized combination of
biomolecules is supplemented in the cell culture medium, a synergistic effect of
the electrical conductivity and biomolecule combination is observed, especially
in the case of highly conducting CNF (7.5% and 10% (w/w))-based nanocomposite
scaffolds. Our findings suggest that electrically conductive scaffolds with
optimized biomolecules in cell culture medium can potentially be used for
successful human meniscal tissue engineering applications.
PMID- 28703123
TI - Amoeba-like self-oscillating polymeric fluids with autonomous sol-gel transition.
AB - In the field of polymer science, many kinds of polymeric material systems that
show a sol-gel transition have been created. However, most systems are
unidirectional stimuli-responsive systems that require physical signals such as a
change in temperature. Here, we report on the design of a block copolymer
solution that undergoes autonomous and periodic sol-gel transition under constant
conditions without any on-off switching through external stimuli. The amplitude
of this self-oscillation of the viscosity is about 2,000 mPa s. We also
demonstrate an intermittent forward motion of a droplet of the polymer solution
synchronized with the autonomous sol-gel transition. This polymer solution bears
the potential to become the base for a type of slime-like soft robot that can
transform its shape kaleidoscopically and move autonomously, which is associated
with the living amoeba that moves forward by a repeated sol-gel transition.
PMID- 28703124
TI - Comparison between the effects of hydrochlorothiazide and indapamide on the
kidney in hypertensive patients inadequately controlled with losartan.
AB - The aim of the study is to compare the effects of hydrochlorothiazide and
indapamide on the kidney in patients with hypertension inadequately controlled
with losartan. A total of 140 patients who met the criteria and inadequately
controlled with losartan 50 mg per day for 2 weeks were randomized in two groups
and administered either hydrochlorothiazide 12.5 mg per day (n=70) or indapamide
(sustained release) 1.5 mg per day (n=70) in combination with losartan 50 mg per
day. Office blood pressure (BP) were collected at baseline and upon each follow
up visit. Creatinine, urine albumin-creatinine ratio (ACR), urine neutrophil
gelatinase-associated lipocalin (NGAL) and renal resistive index (RRI) were also
collected at baseline and at the 24-week follow-up. None of the baseline
characteristics was statistically significantly different between the two groups.
After excluding those patients with office BP uncontrolled, 46 patients in the
hydrochlorothiazide group (45.7% males, 58.8+/-10.8 years) and 44 patients in the
indapamide group (38.4% males, 61.5+/-10.9 years) were analysed. There were
insignificant changes in creatinine and significant decreases in ACR, NGAL and
RRI compared to baseline levels in the two groups. The decrease in ACR (3.8 (0,
28.7) vs 4.2 (0.4, 64.8) mg g-1, P=0.485) was not significantly different between
the two groups, while the decrease in NGAL (16.07+/-7.07 vs 28.77+/-7.64 ng ml-1,
P<0.001) and RRI (0.04+/-0.02 vs 0.07+/-0.04, P<0.001) was more significant in
the indapamide group than in the hydrochlorothiazide group. In conclusion,
indapamide is superior to hydrochlorothiazide to improve renal tubular injury and
renal haemodynamics in combination with losartan in hypertensive patients with
controlled BP.
PMID- 28703125
TI - Flat clathrin lattices are dynamic actin-controlled hubs for clathrin-mediated
endocytosis and signalling of specific receptors.
AB - Clathrin lattices at the plasma membrane coat both invaginated and flat regions
forming clathrin-coated pits and clathrin plaques, respectively. The function and
regulation of clathrin-coated pits in endocytosis are well understood but
clathrin plaques remain enigmatic nanodomains. Here we use super-resolution
microscopy, molecular genetics and cell biology to show that clathrin plaques
contain the machinery for clathrin-mediated endocytosis and cell adhesion, and
associate with both clathrin-coated pits and filamentous actin. We also find that
actin polymerization promoted by N-WASP through the Arp2/3 complex is crucial for
the regulation of plaques but not pits. Clathrin plaques oppose cell migration
and undergo actin- and N-WASP-dependent disassembly upon activation of LPA
receptor 1, but not EGF receptor. Most importantly, plaque disassembly correlates
with the endocytosis of LPA receptor 1 and down-modulation of AKT activity. Thus,
clathrin plaques serve as dynamic actin-controlled hubs for clathrin-mediated
endocytosis and signalling that exhibit receptor specificity.
PMID- 28703126
TI - Radiocarbon constraints on the glacial ocean circulation and its impact on
atmospheric CO2.
AB - While the ocean's large-scale overturning circulation is thought to have been
significantly different under the climatic conditions of the Last Glacial Maximum
(LGM), the exact nature of the glacial circulation and its implications for
global carbon cycling continue to be debated. Here we use a global array of ocean
atmosphere radiocarbon disequilibrium estimates to demonstrate a ~689+/-53 14C-yr
increase in the average residence time of carbon in the deep ocean at the LGM. A
predominantly southern-sourced abyssal overturning limb that was more isolated
from its shallower northern counterparts is interpreted to have extended from the
Southern Ocean, producing a widespread radiocarbon age maximum at mid-depths and
depriving the deep ocean of a fast escape route for accumulating respired carbon.
While the exact magnitude of the resulting carbon cycle impacts remains to be
confirmed, the radiocarbon data suggest an increase in the efficiency of the
biological carbon pump that could have accounted for as much as half of the
glacial-interglacial CO2 change.
PMID- 28703127
TI - Quantitative real-time imaging of glutathione.
AB - Glutathione plays many important roles in biological processes; however, the
dynamic changes of glutathione concentrations in living cells remain largely
unknown. Here, we report a reversible reaction-based fluorescent probe-designated
as RealThiol (RT)-that can quantitatively monitor the real-time glutathione
dynamics in living cells. Using RT, we observe enhanced antioxidant capability of
activated neurons and dynamic glutathione changes during ferroptosis. RT is thus
a versatile tool that can be used for both confocal microscopy and flow cytometry
based high-throughput quantification of glutathione levels in single cells. We
envision that this new glutathione probe will enable opportunities to study
glutathione dynamics and transportation and expand our understanding of the
physiological and pathological roles of glutathione in living cells.
PMID- 28703128
TI - Structural insights into the mycobacteria transcription initiation complex from
analysis of X-ray crystal structures.
AB - The mycobacteria RNA polymerase (RNAP) is a target for antimicrobials against
tuberculosis, motivating structure/function studies. Here we report a 3.2 A
resolution crystal structure of a Mycobacterium smegmatis (Msm) open promoter
complex (RPo), along with structural analysis of the Msm RPo and a previously
reported 2.76 A-resolution crystal structure of an Msm transcription initiation
complex with a promoter DNA fragment. We observe the interaction of the Msm RNAP
alpha-subunit C-terminal domain (alphaCTD) with DNA, and we provide evidence that
the alphaCTD may play a role in Mtb transcription regulation. Our results reveal
the structure of an Actinobacteria-unique insert of the RNAP beta' subunit.
Finally, our analysis reveals the disposition of the N-terminal segment of Msm
sigmaA, which may comprise an intrinsically disordered protein domain unique to
mycobacteria. The clade-specific features of the mycobacteria RNAP provide clues
to the profound instability of mycobacteria RPo compared with E. coli.
PMID- 28703129
TI - Precise inhibitory microcircuit assembly of developmentally related neocortical
interneurons in clusters.
AB - GABA-ergic interneurons provide diverse inhibitions that are essential for the
operation of neuronal circuits in the neocortex. However, the mechanisms that
control the functional organization of neocortical interneurons remain largely
unknown. Here we show that developmental origins influence fine-scale synapse
formation and microcircuit assembly of neocortical interneurons. Spatially
clustered neocortical interneurons originating from low-titre retrovirus-infected
radial glial progenitors in the embryonic medial ganglionic eminence and preoptic
area preferentially develop electrical, but not chemical, synapses with each
other. This lineage-related electrical coupling forms predominantly between the
same interneuron subtype over an extended postnatal period and across a range of
distances, and promotes action potential generation and synchronous firing.
Interestingly, this selective electrical coupling relates to a coordinated
inhibitory chemical synapse formation between sparsely labelled interneurons in
clusters and the same nearby excitatory neurons. These results suggest a link
between the lineage relationship of neocortical interneurons and their precise
functional organization.
PMID- 28703130
TI - Potential increase in coastal wetland vulnerability to sea-level rise suggested
by considering hydrodynamic attenuation effects.
AB - The future of coastal wetlands and their ecological value depend on their
capacity to adapt to the interacting effects of human impacts and sea-level rise.
Even though extensive wetland loss due to submergence is a possible scenario, its
magnitude is highly uncertain due to limited understanding of hydrodynamic and
bio-geomorphic interactions over time. In particular, the effect of man-made
drainage modifications on hydrodynamic attenuation and consequent wetland
evolution is poorly understood. Predictions are further complicated by the
presence of a number of vegetation types that change over time and also
contribute to flow attenuation. Here, we show that flow attenuation affects
wetland vegetation by modifying its wetting-drying regime and inundation depth,
increasing its vulnerability to sea-level rise. Our simulations for an Australian
subtropical wetland predict much faster wetland loss than commonly used models
that do not consider flow attenuation.
PMID- 28703131
TI - EGFR rs11506105 and IFNL3 SNPs but not rs8099917 are strongly associated with
treatment responses in Iranian patients with chronic hepatitis C.
AB - Interferon lambda 3 (IFNL3) and epidermal growth factor receptor (EGFR) single
nucleotide polymorphisms (SNPs) may play a key role in the spontaneous clearance
of hepatitis C virus (HCV) and treatment responses. The aim of this study was to
evaluate the effect of IFNL3 SNPs and EGFR rs11506105 on treatment outcomes in
patients with chronic HCV (CHC). IFNL3 SNPs and EGFR rs11506105 were genotyped by
PCR-restriction fragment length polymorphism and PCR-sequencing, respectively, in
235 naive patients with CHC infection. The frequency of rapid virologic response
(RVR), complete early virologic response (cEVR) and sustained virologic response
(SVR) were 52.3%, 76.2% and 64.7% respectively. The results of this study showed
that RVR was associated with ALT (P=0.015), AST (P=0.020), IFNL3 rs12979860 (CC)
(P=0.043), rs12980275 (AA) (P=1 * 10-4), and EGFR rs11506105 (AA) (P=0.010), and
IFNL3 rs12979860 (CC) (P=0.048), rs12980275 (AA) (P=0.022), and EGFR rs11506105
(AA) (P=0.006) were correlated with cEVR. HCV genotype (P=0.007), IFNL3
rs12979860 (CC) (P=0.023), IFNL3 rs12980275 (AA) (P=1 * 10-4), EGFR rs11506105
(AA) (P=0.005), RVR (P=1 * 10-4), and cEVR (P=0.003) were significant predictors
for SVR. These results, for the first time, revealed that beside IFNL3 SNPs, EGFR
rs11506105 is strongly associated with RVR, cEVR and SVR. EGFR rs11506105 besides
IFNL3 SNPs could predict treatment responses in CHC patients.
PMID- 28703132
TI - Association of a functional TNF variant with Plasmodium falciparum parasitaemia
in a congolese population.
AB - Several studies have provided evidence of both helpful and harmful effects of TNF
on the outcome of Plasmodium falciparum malaria infection. Several TNF
polymorphisms that are located within non-coding regions have been associated
with parasitaemia, mild malaria or severe malaria. We investigated the
association of TNF1304 (rs3093664), TNF-308 (rs1800629), TNF-238 (rs361525) and
TNF-244 (rs673) with mild malaria and symptomatic maximum parasitaemia in a
population-based design (n=310). We obtained nominal evidence for an association
between symptomatic maximum parasitaemia and TNF-308, TNF-238, and TNF-244 on the
one hand, and between the number of mild malaria attacks and TNF-244 on the other
hand. After accounting for multiple tests, we confirmed the association of
symptomatic maximum parasitaemia with TNF-244. We further provide bioinformatics
and experimental evidence that TNF-244 has a cis-regulatory effect. This is the
first report that emphasizes the potential role of TNF-244 in malaria.
PMID- 28703133
TI - Association of autoimmune hepatitis with Src homology 2 adaptor protein 3 gene
polymorphisms in Japanese patients.
AB - Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease characterized
by an autoimmune reaction to hepatocytes. The Src homology 2 adaptor protein 3
(SH2B3) gene is a member of the SH2B family of adaptor proteins that has been
implicated in the integration and regulation of multiple signaling events. SH2B3
is involved in cytokine signaling pathways and serves as a negative mediator of T
cell receptor signaling. Genome-wide association analyses in Caucasians have
linked a missense mutation at rs3184504 in SH2B3 with AIH. Accordingly, four
selected single-nucleotide polymorphisms (SNPs) in the SH2B3 gene were genotyped
in 158 patients with AIH, 327 patients with primary biliary cholangitis, 160
patients with autoimmune pancreatitis, and 325 healthy subjects of Japanese
descent. Although the functional rs3184504 was non-polymorphic in 952 subjects,
the frequency of the minor rs11065904 T allele was significantly decreased in AIH
patients compared with healthy controls (odds ratio (OR)=0.68; corrected
P=0.025). Haplotype 2 (rs2238154 A, rs11065904 T and rs739496 G) was associated
with resistance to AIH (OR 0.67, P=0.021) as well as to autoimmune pancreatitis
(OR=0.70, P=0.035). Our findings suggest that an SNP and haplotype in SH2B3 are
associated with AIH.
PMID- 28703134
TI - Genetic variants underlying vitamin D metabolism and VDR-TGFbeta-1-SMAD3
interaction may impact on HCV progression: a study based on dbGaP data from the
HALT-C study.
AB - Vitamin D deficiency is prevalent in liver disease and vitamin D has been shown
to decrease hepatic fibrosis through an anti-TGFbeta-1/SMAD3 effect mediated by
the vitamin D receptor. Thus, we hypothesized that genetic variants involved in
vitamin D metabolism and/or VDR/TGFbeta-1/SMAD3 interaction could impact on the
progression of chronic HCV. We obtained or imputed genotypes for 40 single
nucleotide polymorphisms (SNPs) located in genes implicated in vitamin D
metabolism from the HALT-C cohort via dbGaP. The HALT-C study followed 692
chronic HCV patients over 4 years, evaluating clinical outcomes including
worsening of fibrosis, hepatic decompensation (gastric/esophageal bleeding,
CTP>7, ascites, spontaneous bacterial peritonitis and encephalopathy),
development of hepatocellular carcinoma, and liver death. We tested the selected
SNPs for association with these outcomes in 681 HALT-C subjects. Eleven SNPs
presented tendency towards significance (P<0.05): four SNPs in DHCR7 related to
with hepatic decompensation (rs4944957, rs12800438, rs3829251 and rs4945008); two
in GC to worsening of fibrosis and liver death (rs7041 and rs222020); two in
CYP2R1 to ascites and hepatocellular carcinoma (rs7116978 and rs1562902); two in
VDR to gastric/esophageal bleeding and hepatocellular carcinoma (rs4516035 and
rs2239186); and one in SMAD3 to worsening of fibrosis and encephalopathy
(rs2118610). Only rs1800469 in TGFB1 was statistically associated with hepatic
decompensation after Bonferroni's correction (P<0.00125). In conclusion,
rs1800469 in TGFB1 was associated to hepatic decompensation in chronic hepatitis
C, while the other 11 described polymorphisms must be evaluated in a larger
cohort to determine the possible role of vitamin D in hepatitis C.
PMID- 28703135
TI - Genome-wide association study of neovascular age-related macular degeneration in
the Thai population.
AB - We performed a genome-wide association study on 377 cases of neovascular age
related macular degeneration (AMD) and 1074 controls to determine the association
of previously reported genetic variants associated with neovascular AMD in the
Thai population. All patients were of Thai ancestry. We confirmed the association
of age-related maculopathy susceptibility 2 (ARMS2) rs10490924 (P=7.38 * 10-17),
HTRA1 rs11200638 (P=5.47 * 10-17) and complement factor H gene (CFH) rs800292
(P=2.53 * 10-8) with neovascular AMD, all loci passing the genome-wide
significance level (P<5.22 * 10-8). We also found association of the previously
reported CFH rs10737680 (P=1.76 * 10-6) locus in the discovery sample. Two loci
not previously reported to be associated with neovascular AMD were selected for
replication in 222 cases and 623 controls. The loci included LINCO1317 rs6733379
and rs2384550 on chromosome 12. LINCO1317 rs6733379 (P=3.85 * 10-2) remained
significantly associated with neovascular AMD after replication. In conclusion,
we confirm that ARMS2, HTRA1 and CFH variants are associated with neovascular AMD
in the Thai population. Findings from this study also suggest that variants
contributing to the susceptibility of neovascular AMD in the Thai population are
mostly similar to other Asians with additional local genetic risks that may
specifically be identified in Thai population.
PMID- 28703136
TI - Dynamic-template-directed multiscale assembly for large-area coating of highly
aligned conjugated polymer thin films.
AB - Solution processable semiconducting polymers have been under intense
investigations due to their diverse applications from printed electronics to
biomedical devices. However, controlling the macromolecular assembly across
length scales during solution coating remains a key challenge, largely due to the
disparity in timescales of polymer assembly and high-throughput printing/coating.
Herein we propose the concept of dynamic templating to expedite polymer
nucleation and the ensuing assembly process, inspired by biomineralization
templates capable of surface reconfiguration. Molecular dynamic simulations
reveal that surface reconfigurability is key to promoting template-polymer
interactions, thereby lowering polymer nucleation barrier. Employing ionic-liquid
based dynamic template during meniscus-guided coating results in highly aligned,
highly crystalline donor-acceptor polymer thin films over large area (>1 cm2) and
promoted charge transport along both the polymer backbone and the pi-pi stacking
direction in field-effect transistors. We further demonstrate that the charge
transport anisotropy can be reversed by tuning the degree of polymer backbone
alignment.
PMID- 28703138
TI - Spin diffusion from an inhomogeneous quench in an integrable system.
AB - Generalized hydrodynamics predicts universal ballistic transport in integrable
lattice systems when prepared in generic inhomogeneous initial states. However,
the ballistic contribution to transport can vanish in systems with additional
discrete symmetries. Here we perform large scale numerical simulations of spin
dynamics in the anisotropic Heisenberg XXZ spin 1/2 chain starting from an
inhomogeneous mixed initial state which is symmetric with respect to a
combination of spin reversal and spatial reflection. In the isotropic and easy
axis regimes we find non-ballistic spin transport which we analyse in detail in
terms of scaling exponents of the transported magnetization and scaling profiles
of the spin density. While in the easy-axis regime we find accurate evidence of
normal diffusion, the spin transport in the isotropic case is clearly super
diffusive, with the scaling exponent very close to 2/3, but with universal
scaling dynamics which obeys the diffusion equation in nonlinearly scaled time.
PMID- 28703139
TI - Erratum.
PMID- 28703137
TI - Platelet function is modified by common sequence variation in megakaryocyte super
enhancers.
AB - Linking non-coding genetic variants associated with the risk of diseases or
disease-relevant traits to target genes is a crucial step to realize GWAS
potential in the introduction of precision medicine. Here we set out to determine
the mechanisms underpinning variant association with platelet quantitative traits
using cell type-matched epigenomic data and promoter long-range interactions. We
identify potential regulatory functions for 423 of 565 (75%) non-coding variants
associated with platelet traits and we demonstrate, through ex vivo and proof of
principle genome editing validation, that variants in super enhancers play an
important role in controlling archetypical platelet functions.
PMID- 28703142
TI - New UK graduates' knowledge of training and service provision within restorative
dentistry - a survey.
AB - Objective To assess new UK graduates' knowledge of training and service provision
within restorative dentistry.Design A national descriptive cross-sectional
survey.Subjects and methods An online survey assessing clinicians' knowledge of
restorative dentistry, who had graduated within the last four years in the UK,
was distributed across the UK via postgraduate dental deaneries. One-hundred
responses were accepted as a sample of a potential population of 4,000.Main
outcome measure How well respondents understood the service provision and
training aspects of the specialty of restorative dentistry.Results The responses
were received from graduates from a variety of dental schools across the UK. Of
those respondents, 41 reported receiving career guidance within restorative
dentistry. 45 new graduates were confident in their understanding of the
specialty, while 53 were confident in the differences between restorative
dentistry and monospecialty training. The respondents appeared unaware regarding
treatment priorities within restorative dentistry departments. Most respondents
felt that receiving teaching on restorative dentistry as a specialty and career
pathway would be beneficial.Conclusion The results suggest that new graduates may
benefit from clarification regarding the specialty of restorative dentistry,
however, caution must be taken due to the limitations of the study.
PMID- 28703143
TI - Feature: The Mouth Care Matters programme.
PMID- 28703145
TI - Use of antibiotics during pregnancy and risk of spontaneous abortion.
AB - Prescribing vigilance.
PMID- 28703144
TI - Occupational health: An underestimation.
PMID- 28703146
TI - Oral cancer: A point to chew upon.
PMID- 28703148
TI - The first dentists sent to the Western Front during the First World War.
AB - At the outbreak of the First World War there was insufficient dental provision
for serving military personnel. No army dental specialists were available
overseas when the troops joined the British Expeditionary Force (BEF). However,
the pain of toothache together with the ensuing limited mastication was
debilitating and demoralising for the British soldiers. The result was that men
were being withdrawn from the front for treatment at base hospitals. This was
limited to extractions by medical officers, which frequently incurred unnecessary
loss of dentition when restorative work would have been preferable. Other
consequences of dental neglect were indigestion and malnutrition. Additionally,
the painful condition of acute necrotising ulcerative gingivitis, then commonly
referred to as 'trench mouth', was prevalent.
PMID- 28703151
TI - Predictability of resin bonded bridges - a systematic review.
AB - Objective The objective of this systematic review is to evaluate the survival
rate of resin bonded bridges (RBBs) and understand the relationship between
various prognostic factors and survival rate.Methods An electronic medline and
hand search were carried out to identify prospective studies on RBBs. Critical
appraisal of the studies was done and data was extracted from selected studies.
Survival rate was estimated with random effect Poissons regression using R
software. Influence of location and luting cements was estimated using odds ratio
and forest plots using CMA software.Results The predicted survival rate for 5 and
10 years are 83.6% and 64.9%, respectively. Functional survival after rebonding
has not been considered in this study. It is expected that functional survival
will be higher than event free survival. Debonding of the restoration (78%) is
the most common type of failure followed by porcelain fracture (13%). Bridges
cemented with Panavia showed the highest survival rate (67%) among the luting
cements analysed for 5 years. Retentive tooth preparation, preparation confined
to enamel, silicoating, supra gingival margins, Ni-Cr or Co-Cr alloys and no
occlusion on pontic in lateral excursions have been reported to be associated
with better survival rates. Anterior RBBs were found to be more retentive than
posterior RBBs. Pooled odds for retention of RBB in anterior segment when
compared to posterior is 1.915 (95%CI - 0.847-4.329). RBBs placed in maxilla were
found to be more retentive than bridges placed in mandible. Pooled odds for
retention of RBB in maxilla when compared to mandible is 1.774 (95%CI - 0.803
3.917).Conclusion and recommendations Replacement of missing teeth with resin
bonded fixed partial dentures is a conservative alternative to conventional fixed
partial dentures and should be included as a treatment option wherever possible.
There are numerous factors that influence the longevity of RBBs. To achieve
successful long-term survival, careful case selection and consideration of
various variables is crucial. There is a clear and urgent need for well
controlled studies to better understand the effects of these prognostic factors.
PMID- 28703153
TI - 'Dam it - it's easy!' - or is it?
AB - Dentists the world over seem to still have issues in making rubber dam
application a routine part of practice, even in situations where patients are
obviously at risk. In this article, the author - who has delivered hundreds of
seminars and hands on tuition in a quick and easy method of dam application (the
'Dam it - it's Easy!' series) to dentists in the UK, Europe, North America and
Asia - highlights the similarity of the misconceptions existing in regard to its
use by dentists the world over. The valuable advantages to the environment in the
dental treatment room by dental dam application are considered underused. The
protection offered by routine rubber dam application is second to none in
situations that are potentially physically hazardous to patients.
PMID- 28703154
TI - Keeping the faith - reporting on antimicrobial resistance in an era of fake news.
AB - '...genuine efforts of well intentioned experts...'
PMID- 28703156
TI - The deceptive complexity of caries.
AB - Exploring the potential value of using data on dental extractions under general
anaesthesia (DGA) to monitor the impact of dental decay in childrenSocioeconomic
inequality in the provision of specific preventive dental interventions among
children in the UK: Children's Dental Health Survey 2003.
PMID- 28703158
TI - Compliance with occupational exposure risk management procedures in a dental
school setting.
AB - Background The Dental Institute at King's College London has recently implemented
changes focusing on infection control, including safety needle provision,
personal protective equipment campaigns, mandatory lectures and formal assessment
for students. We explored the effect of these changes over a five-year
period.Methods We observed 49 clinical consultations in 2010 and 50 in 2014,
examining clinician attire, personal protective equipment, dental operatory
management, sharps hazards and aseptic technique.Results One hundred percent of
operators wore gloves, apron and masks, 94% wore eye protection, 98% had
uncovered wrists and 88% had tidy hair. Ninety-four percent wore safe shoes, 86%
were of appropriate material, and 70-82% demonstrated correct zoning technique.
Safe sharps bin placement improved from 78% to 100%, 92% were not overfilled, and
96% were free from protruding items. Sixty-eight percent of bays were
appropriately barrier wrapped, 78-88% were kept tidy and 96% were free of items
that could have been disposed of immediately following use. Ninety to ninety
eight percent of ultrasonic tips and 64% of burs were removed from handpieces
when not in use.Conclusion Dental healthcare workers are at risk of significant
occupational exposures, which can be minimised by technological advances,
implementation of best practice guidelines, optimisation of the clinical working
environment and reinforcement of infection control policy.
PMID- 28703159
TI - Professionalism... it depends where you're standing.
AB - There is a large body of literature relating to professionalism originating from
a variety of academic disciplines. This has resulted in multiple definitions
being reported, particularly in regards to medical education. This paper aims to
give an overview of the different lenses through which professionalism may be
viewed and how these might impact upon educational objectives and curricular
design for student education.
PMID- 28703163
TI - Oral and oropharyngeal cancer and the role of sexual behaviour: a systematic
review.
AB - Limited and inconsistent evidence that sexual behaviours are a risk factor for
orophangeal cancer.
PMID- 28703164
TI - Death by commissioning.
PMID- 28703167
TI - New evidence supports the role of orthodontics in improving well-being.
PMID- 28703169
TI - Gimme, gimme, gimme... dental policy reform.
AB - Dental politics and subsidy systems for adults in Sweden from 1974 until 2016.
PMID- 28703170
TI - BSPD conference to focus on creative collaboration.
PMID- 28703171
TI - BSDHT and BADT unite to drive change.
PMID- 28703172
TI - Appealing to five senses.
PMID- 28703174
TI - Super stick, super quick!
AB - New Clearfil Universal Bond Quick (UBQ) from Kuraray Noritake works almost
instantly, delivering optimum results without the need to wait. Clearfil UBQ
comprises new rapid bond technology, allowing the dental care professional to
apply and proceed to the drying stage immediately - no more waiting!
PMID- 28703173
TI - Patient management: Ask about habits.
PMID- 28703176
TI - Greek refugee camps: One year on.
PMID- 28703177
TI - A combination technique for relining removable prostheses.
AB - The two major types of resilient lining material include acrylic based lining
material and silicone based lining material. Both these materials have few
inherent disadvantages associated with them. A technique for overcoming the
disadvantages of both the acrylic and silicone based lining materials by using
them in a combination is presented in this article.
PMID- 28703178
TI - An investigation into the variability of primary care oral surgery contracts and
tariffs in England and Wales (2014/2015).
AB - Primary care oral surgery services vary markedly throughout the country but until
now there has been a paucity of data on these services. The British Association
of Oral Surgeons (BAOS) primary care group (the authors) were tasked to gather
data around primary care oral surgery contracts and tariffs and provide evidence
based recommendations on the commissioning of these services. Following a freedom
of information (FOI) request, data were obtained for 27 English local area teams
and seven Welsh local health boards. The data demonstrated both regional and
national variability with respect to primary care oral surgery contracts,
concerning both contract type and level of remuneration. These differences are
discussed and the authors make recommendations for standardising oral surgery
contracts and tariffs.
PMID- 28703179
TI - Postoperative pain after the removal of root canal filling material using
different techniques in teeth with failed root canal therapy: a randomized
clinical trial.
AB - The use of hand files was associated with more postoperative pain.
PMID- 28703180
TI - Socioeconomic inequality in the provision of specific preventive dental
interventions among children in the UK: Children's Dental Health Survey 2003.
AB - Aim To assess socioeconomic inequality regarding specific preventive
interventions (fissure sealants or any treatment to prevent caries) and dental
visits among UK children.Method Data were from the Children's Dental Health
Survey 2003, which included participants from England, Wales, Scotland, and
Northern Ireland. The number of children in the analysis was 2,286. Variables
were sex, age, area of residency (for example, England), mother's education,
family social class, and deprivation level. Descriptive and regression analyses
were performed.Results There were no significant socioeconomic differences in the
use of preventive services. Deprivation and family social class (for example,
intermediate and manual) were significantly associated with less regular dental
visits (odd ratio 0.41, 95% CI [0.28, 0.63]; odd ratio 0.53, 95% CI [0.31, 0.89];
odd ratio 0.37, 95% CI [0.24, 0.58], respectively). Regular dental visits were
associated with reporting preventive care for caries (odds ratio 2.25, 95% CI
[1.45, 3.49]) and with the number of sealed tooth surfaces (rate ratio 1.73, 95%
CI [1.16, 2.60]).Conclusion Despite apparent socioeconomic inequalities in
regular dental visits, there was no significant inequality in using specific
preventive interventions by children in the UK. This finding should be
interpreted with caution considering the relatively small subsample included in
this analysis.
PMID- 28703181
TI - Association Between Helicobacter Pylori Infection and Long-term Outcome in
Patients with Drug-eluting Stent Implantation.
AB - To investigate the relationship between Helicobacter pylori (Hp) infection and
the long-term outcome in acute coronary syndrome (ACS) patients with drug-eluting
stent (DES) implantation and so as to explore the significance of Hp eradication
therapy in preventing major adverse cardiac events (MACE) and upper
gastrointestinal bleeding (UGIB). 539 ACS patients with DES implantation from
January 1, 2010 to December 31, 2012 were analyzed. All the patients were divided
into two groups according to the result of 13C urea breath test. 253 patients
with Hp infection were put into group A (Hp+), and 286 cases without Hp infection
were put into group B (Hp-). Demographic data was collected and all patients went
through biochemical indicators and other routine blood examinations. We explored
the correlations of Hp infection with MACE and UGIB after 3 to 5 years of follow
up using survival analysis. Survival analysis showed that Hp infection was a
predictor of MACE and UGI. Sub-group analysis showed that patients with Hp
eradication therapy had no relationship with MACE but had a lower rate of UGIB
than those without Hp eradication therapy.
PMID- 28703182
TI - Quantum back-action-evading measurement of motion in a negative mass reference
frame.
AB - Quantum mechanics dictates that a continuous measurement of the position of an
object imposes a random quantum back-action (QBA) perturbation on its momentum.
This randomness translates with time into position uncertainty, thus leading to
the well known uncertainty on the measurement of motion. As a consequence of this
randomness, and in accordance with the Heisenberg uncertainty principle, the QBA
puts a limitation-the so-called standard quantum limit-on the precision of
sensing of position, velocity and acceleration. Here we show that QBA on a
macroscopic mechanical oscillator can be evaded if the measurement of motion is
conducted in the reference frame of an atomic spin oscillator. The collective
quantum measurement on this hybrid system of two distant and disparate
oscillators is performed with light. The mechanical oscillator is a vibrational
'drum' mode of a millimetre-sized dielectric membrane, and the spin oscillator is
an atomic ensemble in a magnetic field. The spin oriented along the field
corresponds to an energetically inverted spin population and realizes a negative
effective-mass oscillator, while the opposite orientation corresponds to an
oscillator with positive effective mass. The QBA is suppressed by -1.8 decibels
in the negative-mass setting and enhanced by 2.4 decibels in the positive-mass
case. This hybrid quantum system paves the way to entanglement generation and
distant quantum communication between mechanical and spin systems and to sensing
of force, motion and gravity beyond the standard quantum limit.
PMID- 28703183
TI - Bioengineering: Bile ducts regenerated.
PMID- 28703184
TI - Taxonomy: refine rather than stabilize.
PMID- 28703185
TI - Sustainable development: Manage chemicals and waste globally.
PMID- 28703189
TI - Snyder replies.
PMID- 28703188
TI - Allelic reprogramming of 3D chromatin architecture during early mammalian
development.
AB - In mammals, chromatin organization undergoes drastic reprogramming after
fertilization. However, the three-dimensional structure of chromatin and its
reprogramming in preimplantation development remain poorly understood. Here, by
developing a low-input Hi-C (genome-wide chromosome conformation capture)
approach, we examined the reprogramming of chromatin organization during early
development in mice. We found that oocytes in metaphase II show homogeneous
chromatin folding that lacks detectable topologically associating domains (TADs)
and chromatin compartments. Strikingly, chromatin shows greatly diminished higher
order structure after fertilization. Unexpectedly, the subsequent establishment
of chromatin organization is a prolonged process that extends through
preimplantation development, as characterized by slow consolidation of TADs and
segregation of chromatin compartments. The two sets of parental chromosomes are
spatially separated from each other and display distinct compartmentalization in
zygotes. Such allele separation and allelic compartmentalization can be found as
late as the 8-cell stage. Finally, we show that chromatin compaction in
preimplantation embryos can partially proceed in the absence of zygotic
transcription and is a multi-level hierarchical process. Taken together, our data
suggest that chromatin may exist in a markedly relaxed state after fertilization,
followed by progressive maturation of higher-order chromatin architecture during
early development.
PMID- 28703190
TI - Solar energy: Switch it off on eclipse day.
PMID- 28703191
TI - Overestimate of committed warming.
PMID- 28703192
TI - Precision measurement: Sensing past the quantum limit.
PMID- 28703195
TI - Conflicting evidence for ferroelectricity.
PMID- 28703196
TI - Biogeochemistry: Arctic plants take up mercury vapour.
PMID- 28703197
TI - Research foundations: Philanthropic risks can hit home runs.
PMID- 28703199
TI - Tundra uptake of atmospheric elemental mercury drives Arctic mercury pollution.
AB - Anthropogenic activities have led to large-scale mercury (Hg) pollution in the
Arctic. It has been suggested that sea-salt-induced chemical cycling of Hg
(through 'atmospheric mercury depletion events', or AMDEs) and wet deposition via
precipitation are sources of Hg to the Arctic in its oxidized form (Hg(ii)).
However, there is little evidence for the occurrence of AMDEs outside of coastal
regions, and their importance to net Hg deposition has been questioned.
Furthermore, wet-deposition measurements in the Arctic showed some of the lowest
levels of Hg deposition via precipitation worldwide, raising questions as to the
sources of high Arctic Hg loading. Here we present a comprehensive Hg-deposition
mass-balance study, and show that most of the Hg (about 70%) in the interior
Arctic tundra is derived from gaseous elemental Hg (Hg(0)) deposition, with only
minor contributions from the deposition of Hg(ii) via precipitation or AMDEs. We
find that deposition of Hg(0)-the form ubiquitously present in the global
atmosphere-occurs throughout the year, and that it is enhanced in summer through
the uptake of Hg(0) by vegetation. Tundra uptake of gaseous Hg(0) leads to high
soil Hg concentrations, with Hg masses greatly exceeding the levels found in
temperate soils. Our concurrent Hg stable isotope measurements in the atmosphere,
snowpack, vegetation and soils support our finding that Hg(0) dominates as a
source to the tundra. Hg concentration and stable isotope data from an inland-to
coastal transect show high soil Hg concentrations consistently derived from
Hg(0), suggesting that the Arctic tundra might be a globally important Hg sink.
We suggest that the high tundra soil Hg concentrations might also explain why
Arctic rivers annually transport large amounts of Hg to the Arctic Ocean.
PMID- 28703200
TI - Tayi et al. reply.
PMID- 28703201
TI - Retraction: Oncogenic activity of Cdc6 through repression of the INK4/ARF locus.
AB - This corrects the article DOI: 10.1038/nature04585.
PMID- 28703203
TI - Kill the myth of the miracle machine.
PMID- 28703204
TI - Let's talk about sex robots.
PMID- 28703206
TI - Panda diplomats, smuggled relics and a nuclear-weapons treaty.
PMID- 28703205
TI - Witness gravity's quantum side in the lab.
PMID- 28703207
TI - Massive database of 182,000 leaves is helping predict plants' family trees.
PMID- 28703208
TI - How poverty affects the brain.
PMID- 28703209
TI - Proposed US public-health chief is a champion for women and children.
PMID- 28703210
TI - Ancient-genome studies grapple with Africa's past.
PMID- 28703211
TI - Don't pay prizes for published science.
PMID- 28703212
TI - White House's dwindling science office leaves major research programmes in limbo.
PMID- 28703213
TI - Tricks to mute quantum noise aid hunt for gravitational waves.
PMID- 28703214
TI - Stop Alzheimer's before it starts.
PMID- 28703215
TI - Why planetary scientists want better fake space dirt.
PMID- 28703217
TI - Phase matching as a gate for photon entanglement.
AB - Phase matching is shown to provide a tunable gate that helps discriminate
entangled states of light generated by four-wave mixing (FWM) in optical fibers
against uncorrelated photons originating from Raman scattering. Two types of such
gates are discussed. Phase-matching gates of the first type are possible in the
normal dispersion regime, where FWM sidebands can be widely tuned by high-order
dispersion management, enhancing the ratio of the entangled-photon output to the
Raman noise. The photon-entanglement gates of the second type are created by dual
pump cross-phase-modulation-induced FWM sideband generation and can be tuned by
group-velocity mismatch of the pump fields.
PMID- 28703218
TI - The type VI secretion system sheath assembles at the end distal from the membrane
anchor.
AB - The bacterial Type VI secretion system (T6SS) delivers proteins into target cells
using fast contraction of a long sheath anchored to the cell envelope and wrapped
around an inner Hcp tube associated with the secreted proteins. Mechanisms of
sheath assembly and length regulation are unclear. Here we study these processes
using spheroplasts formed from ampicillin-treated Vibrio cholerae. We show that
spheroplasts secrete Hcp and deliver T6SS substrates into neighbouring cells.
Imaging of sheath dynamics shows that the sheath length correlates with the
diameter of spheroplasts and may reach up to several micrometres. Analysis of
sheath assembly after partial photobleaching shows that subunits are exclusively
added to the sheath at the end that is distal from the baseplate and cell
envelope attachment. We suggest that this mode of assembly is likely common for
all phage-like contractile nanomachines, because of the conservation of the
structures and connectivity of sheath subunits.
PMID- 28703219
TI - Genome-wide association and expression quantitative trait loci studies identify
multiple susceptibility loci for thyroid cancer.
AB - Thyroid cancer is the most common cancer in Korea. Several susceptibility loci of
differentiated thyroid cancer (DTC) were identified by previous genome-wide
association studies (GWASs) in Europeans only. Here we conducted a GWAS and a
replication study in Koreans using a total of 1,085 DTC cases and 8,884 controls,
and validated these results using expression quantitative trait loci (eQTL)
analysis and clinical phenotypes. The most robust associations were observed in
the NRG1 gene (rs6996585, P=1.08 * 10-10) and this SNP was also associated with
NRG1 expression in thyroid tissues. In addition, we confirmed three previously
reported loci (FOXE1, NKX2-1 and DIRC3) and identified seven novel susceptibility
loci (VAV3, PCNXL2, INSR, MRSB3, FHIT, SEPT11 and SLC24A6) associated with DTC.
Furthermore, we identified specific variants of DTC that have different effects
according to cancer type or ethnicity. Our findings provide deeper insight into
the genetic contribution to thyroid cancer in different populations.
PMID- 28703220
TI - Tumour-induced osteomalacia.
AB - Tumour-induced osteomalacia (TIO), also known as oncogenic osteomalacia, is a
rare paraneoplastic disorder caused by tumours that secrete fibroblast growth
factor 23 (FGF23). Owing to the role of FGF23 in renal phosphate handling and
vitamin D synthesis, TIO is characterized by decreased renal tubular reabsorption
of phosphate, by hypophosphataemia and by low levels of active vitamin D. Chronic
hypophosphataemia ultimately results in osteomalacia (that is, inadequate bone
mineralization). The diagnosis of TIO is usually suspected when serum phosphate
levels are chronically low in the setting of bone pain, fragility fractures and
muscle weakness. Locating the offending tumour can be very difficult, as the
tumour is often very small and can be anywhere in the body. Surgical removal of
the tumour is the only definitive treatment. When the tumour cannot be located or
when complete resection is not possible, medical treatment with phosphate salts
or active vitamin D is necessary. One of the most promising emerging treatments
for unresectable tumours that cause TIO is the anti-FGF23 monoclonal antibody
KRN23. The recent identification of a fusion of fibronectin and fibroblast growth
factor receptor 1 (FGFR1) as a molecular driver in some tumours not only sheds
light on the pathophysiology of TIO but also opens the door to a better
understanding of the transcription, translocation, post-translational
modification and secretion of FGF23, as well as suggesting approaches to targeted
therapy. Further study will reveal if the FGFR1 pathway is also involved in
tumours that do not harbour the translocation.
PMID- 28703221
TI - Manipulation of nuclear architecture through CRISPR-mediated chromosomal looping.
AB - Chromatin looping is key to gene regulation, yet no broadly applicable methods to
selectively modify chromatin loops have been described. We have engineered a
method for chromatin loop reorganization using CRISPR-dCas9 (CLOuD9) to
selectively and reversibly establish chromatin loops. We demonstrate the power of
this technology to selectively modulate gene expression at targeted loci.
PMID- 28703222
TI - Transparency of genetic testing services for 'health, wellness and lifestyle':
analysis of online prepurchase information for UK consumers.
AB - The declining cost of DNA sequencing has been accompanied by a proliferation of
companies selling 'direct-to-consumer genetic testing' (DTC-GT) services. Many of
these are marketed online as tools for enabling citizens to make more informed
decisions about their health, wellness and lifestyle. We assessed the
'information for consumers' provided by these companies at the prepurchase stage,
which could influence initial decisions to part with money, data or tissue
samples. A scoping exercise revealed 65 DTC-GT companies advertising their
services online to consumers in the United Kingdom, of which 15 met our inclusion
criteria. We benchmarked their consumer information against the good practice
principles developed by the UK Human Genetics Commission (HGC). No provider
complied with all the HGC principles and overall levels of compliance varied
considerably. Although consent for testing was discussed by all but one company,
information about data reuse for research or other purposes was often sparse and
consent options limited or unclear. Most did not provide supplementary support
services to help users better understand or cope with the implications of test
results. We provide recommendations for updating the preconsumer transparency
aspects of the HGC guidelines to ensure their fitness-for-purpose in this rapidly
changing market. We also recommend improving coordination between relevant
governance bodies to ensure minimum standards of transparency, quality and
accountability. Although DTC-GT has many potential benefits, close partnership
between consumers, industry and government, along with interdisciplinary science
input, are essential to ensure that these innovations are used ethically and
responsibly.
PMID- 28703224
TI - Basic research: New cardiomyocyte formation in adult mouse hearts.
PMID- 28703223
TI - Unmasking the molecular link between arrhythmogenic cardiomyopathy and Brugada
syndrome.
AB - The intercalated discs that connect cardiomyocytes control cell-to-cell adhesion
and communication. Several macromolecular structures (desmosomes, fascia adherens
junctions, gap junctions, and sodium-channel complexes) coexist in, and confer
their mechanical and electrical properties to, the intercalated disc.
Traditionally, each structure was assumed to have a unique function in the
intercalated disc. However, growing evidence suggests that these complexes act
together in intercellular communication and adhesion, forming a single structural
and functional entity - the connexome. This nascent idea has provided conceptual
support for the overlapping of two diseases based on disturbance of the
intercalated disc - arrhythmogenic cardiomyopathy (ACM) and Brugada syndrome
(BrS). In this Perspectives article, we present the latest findings about the
functions of, and interactions between, the structures of the intercalated disc
that support the concept of the connexome. We also summarize the genetic,
molecular, and pathophysiological mechanisms underlying ACM and BrS, focusing on
the overlap between these diseases.
PMID- 28703225
TI - Auger electron emission initiated by the creation of valence-band holes in
graphene by positron annihilation.
AB - Auger processes involving the filling of holes in the valence band are thought to
make important contributions to the low-energy photoelectron and secondary
electron spectrum from many solids. However, measurements of the energy spectrum
and the efficiency with which electrons are emitted in this process remain
elusive due to a large unrelated background resulting from primary beam-induced
secondary electrons. Here, we report the direct measurement of the energy spectra
of electrons emitted from single layer graphene as a result of the decay of deep
holes in the valence band. These measurements were made possible by eliminating
competing backgrounds by employing low-energy positrons (<1.25 eV) to create
valence-band holes by annihilation. Our experimental results, supported by
theoretical calculations, indicate that between 80 and 100% of the deep valence
band holes in graphene are filled via an Auger transition.
PMID- 28703226
TI - A paper/polymer hybrid CD-like microfluidic SpinChip integrated with DNA
functionalized graphene oxide nanosensors for multiplex qLAMP detection.
AB - A paper/poly(methyl methacrylate) (PMMA) hybrid CD-like microfluidic SpinChip
integrated with DNA probe-functionalized graphene oxide (GO) nanosensors was
developed for multiplex quantitative LAMP detection (mqLAMP). This approach can
simply and effectively address a major challenging problem of multiplexing in
current LAMP methods.
PMID- 28703227
TI - An enzyme-free DNA walker that moves on the surface of functionalized magnetic
microparticles and its biosensing analysis.
AB - An enzyme-free stochastic DNA walker propelled by a single catalytic or double
catalytic DNA assembly has been constructed. The application of the proposed DNA
walking biosensor was successfully expanded to the detection of DNA and the
enzymatic activity of T4 polynucleotide kinase.
PMID- 28703230
TI - Visible-light-induced oxidative formylation of N-alkyl-N-(prop-2-yn-1-yl)anilines
with molecular oxygen in the absence of an external photosensitizer.
AB - Visible-light-induced oxidative formylation of N-alkyl-N-(prop-2-yn-1-yl)anilines
with molecular oxygen in the absence of an external photosensitizer was developed
and afforded the corresponding formamides in good yields under mild conditions.
The investigation of the mechanism disclosed that both the starting material and
the product act as photosensitizers, and 1O2 and O2- are generated through energy
transfer and a single electron transfer pathway and play an important role in the
reaction.
PMID- 28703231
TI - Tracking the FeIV(O) intermediate and O-O bond formation of a nonheme iron
catalyst for water oxidation.
AB - To identify the short-lived, highly-active iron intermediate generated in situ
for water oxidation, we describe here a new complex 1 by subtle modulation of the
TPA ligand and succeed in capturing the high-valent FeIV(O) species, which is
responsible for the O-O bond formation and oxygen evolution with higher
efficiency.
PMID- 28703232
TI - UV-induced single-crystal-to-single-crystal conversion from a coordination ladder
to a two-dimensional network through an intermolecular carbon-carbon coupling
reaction.
AB - UV irradiation of a ladder-like coordination polymer induces a stereospecific [2
+ 2] photocycloaddition reaction of each pair of adjacent olefinic ligands from
neighboring coordination ladders and thus affords a unique two-dimensional
coordination network in a single-crystal-to-single-crystal manner. The conversion
exhibits photocontrolled fluorescence.
PMID- 28703233
TI - Copper complexes with dissymmetrically substituted bis(thiosemicarbazone) ligands
as a basis for PET radiopharmaceuticals: control of redox potential and
lipophilicity.
AB - Copper(ii) bis(thiosemicarbazone) derivatives have been used extensively in
positron emission tomography (PET) to image hypoxia and blood flow and to
radiolabel cells for cell tracking. These applications depend on control of redox
potentials and lipophilicity of the bis(thiosemicarbazone) complexes, which can
be adjusted by altering peripheral ligand substituents. This paper reports the
synthesis of a library of new dissymmetrically substituted bis(thiosemicarbazone)
ligands by controlling the condensation reactions between dicarbonyl compounds
and 4-substituted-3-thiosemicarbazides or using acetal protection. Copper
complexes of the new ligands have been prepared by reaction with copper acetate
or via transmetallation of the corresponding zinc complexes, which are convenient
precursors for the rapid synthesis of radio-copper complexes. Well-defined
structure-activity relationships linking ligand alkylation patterns with redox
potential and lipophilicity of the complexes are reported.
PMID- 28703235
TI - Lattice symmetries and the topologically protected transport of colloidal
particles.
AB - The topologically protected transport of colloidal particles on top of periodic
magnetic patterns is studied experimentally, theoretically, and with computer
simulations. To uncover the interplay between topology and symmetry we use
patterns of all possible two dimensional magnetic point group symmetries with
equal lengths lattice vectors. Transport of colloids is achieved by modulating
the potential with external, homogeneous but time dependent magnetic fields. The
modulation loops can be classified into topologically distinct classes. All loops
falling into the same class cause motion in the same direction, making the
transport robust against internal and external perturbations. We show that the
lattice symmetry has a profound influence on the transport modes, the
accessibility of transport networks, and the individual transport directions of
paramagnetic and diamagnetic colloidal particles. We show how the transport of
colloidal particles above a two fold symmetric stripe pattern changes from
universal adiabatic transport at large elevations via a topologically protected
ratchet motion at intermediate elevations toward a non-transport regime at low
elevations. Transport above four-fold symmetric patterns is closely related to
the two-fold symmetric case. The three-fold symmetric case however consists of a
whole family of patterns that continuously vary with a phase variable. We show
how this family can be divided into two topologically distinct classes supporting
different transport modes and being protected by proper and improper six fold
symmetries. We discuss and experimentally demonstrate the topological transition
between both classes. All three-fold symmetric patterns support independent
transport directions of paramagnetic and diamagnetic particles. The similarities
and the differences in the lattice symmetry protected transport of classical over
damped colloidal particles versus the topologically protected transport in
quantum mechanical systems are emphasized.
PMID- 28703236
TI - Organic selenocyanates as strong and directional chalcogen bond donors for
crystal engineering.
AB - Organic bis(selenocyanate) derivatives act as powerful chalcogen bond donors for
the elaboration of 1D extended structures upon co-crystallization with 4,4'
bipyridine as a ditopic chalcogen bond acceptor.
PMID- 28703237
TI - Stabilizing bubble and droplet interfaces using dipeptide hydrogels.
AB - Hydrophobic dipeptide molecules can be used to create interfacial films covering
bubbles and droplets made from a range of oils. At high pH, the dipeptide
molecules form micelles which transform into a hydrogel of fibres in response to
the addition of salt. We characterize the properties of the hydrogel for two
different salt (MgSO4) concentrations and then we use these gels to stabilize
interfaces. Under high shear, the hydrogel is disrupted and will reform around
bubbles or droplets. Here, we reveal that at low dipeptide concentration, the gel
is too weak to prevent ripening of the bubbles; this then reduces the long-term
stability of the foam. Under the same conditions, emulsions prepared from some
oils are highly stable. We examine the wetting properties of the oil droplets at
a hydrogel surface as a guide to the resulting emulsions.
PMID- 28703239
TI - Reaction screening and optimization of continuous-flow atropine synthesis by
preparative electrospray mass spectrometry.
AB - Preparative electrospray (ES) exploits the acceleration of reactions in charged
microdroplets to perform a small scale chemical synthesis. In combination with on
line mass spectrometric (MS) analysis, it constitutes a rapid screening tool to
select reagents to generate specific products. A successful reaction in
preparative ES triggers a refined microfluidic reaction screening procedure which
includes the optimization for stoichiometry, temperature and residence time. We
apply this combined approach for refining a flow synthesis of atropine. A
successful preparative ES pathway for the synthesis of the phenylacetyl ester
intermediate, using tropine/HCl/phenylacetyl chloride, was optimized for solvent
in both the preparative ES and microfluidics flow systems and a base screening
was conducted by both methods to increase atropine yield, increase percentage
conversion and reduce byproducts. In preparative ES, the first step yielded 55%
conversion (judged using MS) to intermediate and the second step yielded 47%
conversion to atropine. When combined in two discrete steps in continuous-flow
microfluidics, a 44% conversion of the starting material and a 30% actual yield
of atropine were achieved. When the reactions were continuously telescoped in a
new form of preparative reactive extractive electrospray (EES), atropine was
synthesized with a 24% conversion. The corresponding continuous-flow
microfluidics experiment gave a 55% conversion with an average of 34% yield in 8
min residence time. This is the first in depth study to utilize telescoped
preparative ES and the first use of dual ESI emitters for multistep synthesis.
PMID- 28703240
TI - ORR viability of alumina-supported platinum nanocluster: exploring oxidation
behaviour by DFT.
AB - While alumina-supported platinum particles are versatile for several oxidation
reactions, their viability as ORR catalysts has not been explored to date.
Therefore, to assess the prospects of alumina-supported platinum nanoclusters in
ORRs, a systematic DFT study has been carried out to explore the oxidation
behavior of a Ptn@Al2O3 (n = 1-7, 10) cluster. The results are compared with the
oxidation behavior of the corresponding gas phase platinum cluster and that of an
extended Pt(111) slab. Both supported and unsupported clusters activate adsorbed
oxygen molecules and energetically favor dissociative chemisorption of oxygen,
leading to stable oxide formation with Pt-O-Pt linkages. However, the influence
of the alumina substrate downshifts the d-band centre of the platinum cluster,
which not only reduces the reaction enthalpy of oxidation by 8-10%, but also
elongates the Pt-O bond of the oxide product by 3-8%. These observations indicate
that removal of oxide will be relatively easier for supported clusters than for
unsupported clusters. Cluster binding is found to sustain during oxidation, as
oxidation of the platinum host cluster results in reduction of the distance
between the cluster and support surface. While the gas phase Pt10 cluster does
not show any similarity to the oxidation behavior shown by THE Pt(111) slab, the
Pt10@Al2O3 cluster reveals close resemblance. Both the Pt(111) slab and
Pt10@Al2O3 cluster form similar oxide products, having tri-coordinated oxygen
with comparable Pt-O bond distances. The observed resemblance has been attributed
to the similarity in the electronic structure and d-band centre position of the
platinum surface and alumina-supported Pt10 cluster. Whilst this similar
oxidation behaviour of the Pt10@Al2O3 cluster endorses its viability as an ORR
catalyst, further modulation of this catalyst is desirable to improve its
potential.
PMID- 28703241
TI - Microwave induced "egg yolk" structure in Cr/V-MIL-53.
AB - Using a one pot microwave procedure, mixed-metal "egg yolk" MOFs are created,
with a core of (Cr/V)-MIL-53 and a shell of Cr-MIL-53. In contrast, the
solvothermal method produces homogeneous mixed-metal MOFs. The influence of Cr
and V on the flexibility and breathing was studied via T-XRPD and CO2 adsorption
measurements.
PMID- 28703244
TI - Photoreactions of 2-(furan-2-yl)-3-hydroxy-4H-chromen-4-one and 3-hydroxy-2
(thiophene-2-yl)-4H-chromen-4-one using cyclohexane and acetonitrile as solvents.
AB - Photolysis of the titled chromenones was carried out at their longest absorption
band (~360 nm) using cyclohexane (CH) and acetonitrile (ACN) as solvents, in both
aerated and de-aerated solutions. Different dimeric photoproducts were formed
with both chromenones in aerated solutions. On photolysing 2-(furan-2-yl)-3
hydroxy-4H-chromen-4-one (FHC) in aerated cyclohexane, 2-(furan-2-yl)-2-{[2
(furan-2yl)-4-oxo-4H-chromen-3-yl]oxy}-2H-chromene-3,4-dione (a dehydrodimer) was
formed, and on photolysing 3-hydroxy-2-(thiophene-2-yl)-4H-chromen-4-one (THC) in
aerated ACN, a different dimeric product was isolated and identified. The
corresponding 3-aryl-3-hydroxy-1,2-indandiones were also detected with FHC in ACN
and with THC in CH, in addition to the dimeric products in both cases. On the
other hand, in the de-aerated solutions, only the corresponding 1,2-indandiones
were detected. 3-(Furan-2-yl)isobenzofuran-1(3H)-one as a secondary product was
also detected with FHC in both solvents. An attempt was made to isolate the
spectra of the photoproducts in situ. Excited State Intramolecular Proton
Transfer (ESIPT) and Excited State Intramolecular Charge Transfer (ESICT)
processes complicate the photodynamics of the reaction, making it difficult to
predict the mechanisms of the photoreactions. However, tentative mechanisms have
been proposed for the formation of the photoproducts.
PMID- 28703245
TI - Blue-light-promoted carbon-carbon double bond isomerization and its application
in the syntheses of quinolines.
AB - A blue-light-promoted carbon-carbon double bond isomerization in the absence of
any photoredox catalyst is reported. It provides rapid access to a series of
quinolines in good to excellent yields under simple aerobic conditions. The
protocol is direct, catalyst-free and operationally convenient.
PMID- 28703246
TI - Selective construction of polycyclic spirooxindoles via a Cu(OTf)2/HOTf-catalyzed
domino reaction of o-arylalkynylacetophenones and 3-phenacylideneoxindoles.
AB - Under the combined catalysis of Cu(OTf)2/HOTf, the domino annulation reaction of
o-arylalkynyl acetophenones with 3-phenacylideneoxindoles in refluxing
acetonitrile selectively afforded functionalized spiro[indoline-3,7'
tetrapheno[7,6-bc]furans] and spiro[indeno[1,2-b]naphtho[2,1-d]furan-7,3'
indolines] depending on the electronic effect of the substituents on both
substrates.
PMID- 28703248
TI - Immunoassay quantification using surface-enhanced fluorescence (SEF) tags.
AB - Fluorescence-based immonoassays are widely used in several areas, ranging from
basic biomedical research to disease diagnostics. A variety of new probes have
been developed recently to address some limitations in typical assays performed
with organic dyes. Ideally, new fluorescence tags that allow quantification with
a low limit of detection are highly desired. In this work, the surface-enhanced
fluorescence (SEF) phenomenon was explored in the development of tags for
Immunoglobulin-M (IgM) detection. Shell-isolated gold nanoparticles (Au-SHINs)
with 100 nm core size and a 10 nm silica shell were synthesized. These particles
contain an outermost thin fluorescent layer of nile blue (NB) that was further
coated by another 5 nm of silica (SEF tags). The outer silica shell was then
functionalized with antibodies to allow the detection of IgM as in typical
immunological sandwich assays. IgM concentrations down to the 10 ng mL-1 mark
were successfully detected. A linear dependence between the average fluorescence
intensity and the IgM concentration was found.
PMID- 28703250
TI - Correction: Finite cohesion due to chain entanglement in polymer melts.
AB - Correction for 'Finite cohesion due to chain entanglement in polymer melts' by
Shiwang Cheng et al., Soft Matter, 2016, 12, 3340-3351.
PMID- 28703251
TI - Correction: Nonlinear rheology of entangled polymers at turning point.
AB - Correction for 'Nonlinear rheology of entangled polymers at turning point' by Shi
Qing Wang et al., Soft Matter, 2015, 11, 1454-1458.
PMID- 28703252
TI - Metal-coated thermosalient crystals as electrical fuses.
AB - Silver-coated 1,2,4,5-tetrabromobenzene crystals, a thermosalient compound, are
presented as novel electrical fuse materials. These electrically conductive
crystals exhibit linear characteristics up to a threshold value where the
resistive heating triggers their phase transformation. This causes mechanical
motion of the crystals with immediate circuit breakage. The concept described
here opens new avenues for next-generation electrical fuses.
PMID- 28703255
TI - Contorted polycyclic aromatic hydrocarbons with cove regions and zig-zag edges.
AB - A series of tetrapyrene-fused benzocoronenes was synthesized by a "bottom-up"
approach, which offers a facile access to extended polycyclic aromatic
hydrocarbons with concave pi-surfaces, cove regions and zig-zag edges.
PMID- 28703256
TI - Can photoacoustic imaging quantify surface-localized J-aggregating nanoparticles?
AB - We investigate the feasibility of photoacoustic (PA) imaging to quantify the
concentration of surface-localized nanoparticles, using tissue-mimicking phantoms
and imaging with a commercial PA instrument at 815 nm and a linear-array
transducer at a center frequency of 40 MHz. The nanoparticles were J-aggregating
porphysomes (JNP) comprising self-assembling, all-organic porphyrin-lipid
micelles with a molar absorption coefficient of 8.7*108 cm-1 M-1 at this
wavelength. The PA signal intensity versus JNP areal concentration followed a
sigmoidal curve with a reproducible linear range of ~17 fmol/mm2 to 11
pmol/mm2, i.e., ~3 orders of magnitude with +/-34% error. For physiologically
relevant conditions (i.e., optical scattering-dominated tissues: transport albedo
>0.8) and JNP concentrations above ~330 fmol/mm2, the PA signal depends only on
the nanoparticle concentration. Otherwise, independent measurement of the optical
absorption and scattering properties of the underlying tissue is required for
accurate quantification. The implications for surface PA imaging, such as in the
use of targeted nanoparticles applied topically to tissue as in endoscopic
diagnosis, are considered.
PMID- 28703257
TI - Analysis of skin blood microflow oscillations in patients with rheumatic
diseases.
AB - Laser Doppler flowmetry (LDF) has been applied for the assessment of variation in
blood microflows in patients with rheumatic diseases and healthy volunteers.
Oscillations of peripheral blood microcirculation observed by LDF have been
analyzed utilizing a wavelet transform. A higher amplitude of blood microflow
oscillations has been observed in a high frequency band (over 0.1 Hz) in patients
with rheumatic diseases. Oscillations in the high frequency band decreased in
healthy volunteers in response to the cold pressor test, whereas lower frequency
pulsations prevailed in patients with rheumatic diseases. A higher perfusion rate
at normal conditions was observed in patients, and a weaker response to cold
stimulation was observed in healthy volunteers. Analysis of blood microflow
oscillations has a high potential for evaluation of mechanisms of blood flow
regulation and diagnosis of vascular abnormalities associated with rheumatic
diseases.
PMID- 28703258
TI - [Extend the training to psychiatrist!]
PMID- 28703259
TI - [Evaluation of referral and intervention patterns at the psychiatric emergency
service, Utrecht 2009-2015].
AB - BACKGROUND: Emergency psychiatric care in the Netherlands is provided mainly by
community mental health services. Although these emergency services vary in their
approach per region, they show many similarities: they tend to receive referrals
from the same type of agencies and they practice similar techniques of crisis
management.
AIM: To identify some of the patterns that appear in the type of
psychiatric problems encountered, the type of referral agencies involved and in
the intervention strategies practiced by the psychiatric emergency service in
Utrecht.
METHOD: We studied the medical records of 938 crisis assessments
compiled during five measurement periods between 2009 and 2015. From all these
crisis assessments we selected one sample relating to patients coming only from
the city of Utrecht - 'model city Utrecht' - and a second sample consisting only
of patients referred either by HAP (emergency primary care), the police or a
general hospital. Then, by using cross-tabulation and a multinomial logistic
regression analyses, we were able to identify associations between the type of
referral agency, the type of referral problem and the type of intervention.
RESULTS: Patients referred by the police were more often forcefully admitted
(compulsory admission: 27%) than patients referred by general practitioners (6%);
most of these patients were then treated as outpatients (83%). Another pattern
that emerged, was that confused or aggressive patients were admitted to hospital
more frequently than suicidal patients (26%, 29% and 8% respectively).
CONCLUSION: Our study and current trends in the clinical practice operated by the
emergency psychiatric services reveal significant correlations between the type
of referrals and the type of intervention. However, further research is needed in
order to develop the 'best practice' for emergency psychiatric care in the
future.
PMID- 28703260
TI - [Publish & Perish; research on research and researchers].
AB - BACKGROUND: In the last years many people have questioned the reliability of
research results and the societal relevance of much of today's clinical research;
they are critical too about the current publication culture in which scientists
are judged according to the number of articles they have published, impact
factors and citations.
AIM: To make a close study of the publication culture
that now prevails in the Dutch biomedical sciences.
METHOD: Discussion of
results described in the thesis entitled 'Publish and Perish; research on
research and researchers'.
RESULTS: To investigate what 'pressure to
publish' is, we designed the Publication Pressure Questionnaire. In addition, in
a group of 437 professors, we found a relationship between 'pressure to publish'
and burnout; about 25% of the professors reported having suffered from severe
burnout. We used focus groups to discover the factors that scientists consider
are harmful in today's publication culture. They mentioned aspects such as impact
factors, problems with research funding, authorship of articles, publication
bias, emphasis on quantity rather than quality and 'domineering egos'. Next, we
sought the views of 400 Dutch psychiatrists on the influence of pharmaceutical
sponsorship on clinical trials. The psychiatrists seem to overlook the effects
that pharmaceutical sponsoring might have on research results, but were more
critical of results that appeared to be 'too good to be true'. A character study
of more than 500 biomedical professionals revealed a link between scientific
misconduct and pressure to publish; Machiavellian characteristics seemed to be
associated with this misconduct. Finally, the author of the thesis (with 'tongue
in cheek') describes a new psychiatric disorder which he calls 'publiphilia
impactfactorius', defined as a disorder affecting biomedical professionals
characterised by narcissistic, psychopathic, manipulative and emotionally
unstable traits, whose egos are focused primarily on publication and high
citation scores.
CONCLUSION: The thesis demonstrates that on the one hand
scientists should look critically at new research so that they can assess its
value, but on the other hand they must be ready to support new research, even
though most results are likely to require later revision and updating. In spite
of the shortcomings of many published research results, they are after all, the
best we have at a particular moment.
PMID- 28703261
TI - [Negative symptoms and an interruption in the life-line; recovery from passivity
and apathy involves adaptions and risk-taking].
AB - BACKGROUND: Up till now, the experiences of people recovering from psychotic
states and particularly from negative symptoms have scarcely been integrated into
current scientific knowledge of recovery.
AIM: To contribute to the
integration of scientific knowledge about recovery processes by creating an up-to
date model of negative symptoms.
METHOD: In our article we report the views
and comments of an expert patient and a psychiatrist regarding crucial aspects of
the recovery process of the patient who had experienced a long period of
passivity.
RESULTS: Recovery seems to be aided by a number of 'soft'
factors. The damage caused by the interruption in a patient's life-line has to be
limited as far as possible. Patients must be given the opportunity to adjust to
the new situation in which they find themselves. We describe various ways of
encouraging interaction and exploration. Patients need to be presented with
relevant samples of recovery so that they become optimistic about future
improvements in their own mental health.
CONCLUSION: The approach outlined
in this article is likely to contribute to a better understanding of this
precarious mental health state.
PMID- 28703262
TI - [Adequacy of treatment for chronic anxiety or depression; an exploratory study of
treatment practice].
AB - BACKGROUND: Many patients with anxiety or depression receiving specialised
outpatient treatment at mental health centres do not fully recover. Relapse and
chronic course are common. This raises questions about the adequacy of the
treatment they receive.
AIM: To obtain insight into the type and length of
the treatment given to patients with chronic anxiety or depression.
METHOD:
We collected data as part of a national study involving 12 mental health trusts.
To be included in the study, patients had to satisfy certain criteria: they had
to have received specialised treatment for anxiety or depression for at least two
years and there had to be concerns whether these patients would benefit from
further treatment in this setting. We gathered information about patient
characteristics, diagnosis and treatment history.
RESULTS: On the basis of
our selection criteria, 268 patients participated in our study; 65% of the
patients were female. Patients were grouped in three categories: 67% were
suffering from major depression, 25% from anxiety disorder and 8% from comorbid
anxiety and depression. On average, patients had been treated for six years. More
than one third of patients had received poor-quality treatment: treatment in the
form of psychotherapy and/or pharmacotherapy had not been carried out in
accordance with treatment guidelines.
CONCLUSION: In practice, much current
treatment falls short of expectations. In particular, pharmacotherapy for
depression needs to be improved. Longer periods of treatment should be evaluated
at least once every six months.
PMID- 28703263
TI - [High and intensive care three years later; an evaluation of the experiences of
patients and employees and the effect on coercive measures in psychiatry].
AB - BACKGROUND: As part of the national campaign against the use of coercive measures
in psychiatry, the Mental Health Service in Eindhoven set up the first modern
high and intensive care centre (HIC) in Eindhoven in 2012. AIM: To study the
progress of the numbers on coercive measures, and to evaluate the experiences of
patients and treatment team members after working for three years according to
the HIC model. METHOD: We analysed the registration data, carried out a short
survey and conducted interviews. RESULTS: We found that the number of coercive
measures used between 2012 and 2015 had declined by 42%. Patients generally had a
positive attitude to the treatment they had received. They appreciated the role
played by the team and were pleased to have had access to modern technology. Team
members had a positive attitude to working with the HIC model. CONCLUSION: The
main goals of working according to the new HIC model have been achieved. However,
it should be possible to increase cooperation with mobile teams, develop more
links with patients' next-of-kin and make wider use of modern technology.
PMID- 28703264
TI - [Simple is not always easy: genetics in general psychiatry].
AB - Many of the patients who attend the outpatient mental health clinics already have
a long history of psychiatric problems. Their symptoms seem easy to classify, but
the misdiagnosis of the patients' underlying problems can lead to a long series
of costly referrals as inpatients or to an ineffective treatment outcome. In this
article we focus on three patients whose history and background circumstances had
been analysed in detail and who had also been subjected to a genetic analysis.
The analyses pointed to an etiology-based diagnosis which had important
implications for their future treatment and its outcome.
PMID- 28703265
TI - Noncompaction may not only be non-isolated but also myopathic. Commentary to the
article: "Left ventricular non-compaction associated with hypertrophic
cardiomyopathy in the same patient".
PMID- 28703266
TI - A hybrid treatment of Kommerell diverticulum saccular aneurysm in a patient with
subclavian steal syndrome.
PMID- 28703267
TI - Restrictive cardiomyopathy due to novel desmin gene mutation.
PMID- 28703268
TI - Electrical storm secondary to theophylline prescription in a patient with
implantable cardioverter defibrillator.
PMID- 28703269
TI - Intravascular ultrasound in cocaine-induced myocardial infarction complicated
with left coronary artery dissection.
PMID- 28703270
TI - Acute myocardial infarction due to embolisation from the thrombosed coronary
artery fistula between the right coronary artery and the left atrium.
PMID- 28703271
TI - Silent early migration of a Figulla(r) septal occluder into the left ventricle.
PMID- 28703272
TI - Left ventricular non-compaction and hypertrophic cardiomyopathy: two overlapping
diseases or two manifestations of the same cardiomyopathy? Response to the letter
concerning the article: "Left ventricular non-compaction associated with
hypertrophic....
PMID- 28703273
TI - A case of idiopathic angioedema exacerbated by angiotensin receptor blocker
administration.
PMID- 28703275
TI - Predictors of cognitive function in patients with hypothalamic hamartoma
following stereotactic radiofrequency thermocoagulation surgery.
AB - OBJECTIVE: To determine the predictors of cognitive function in patients with
drug-resistant gelastic seizures (GS) related to hypothalamic hamartoma (HH)
before and after stereotactic radiofrequency thermocoagulation surgery (SRT).
METHODS: We studied 88 patients with HH who underwent SRT between October 1997
and December 2014. Patients received neuropsychological tests preoperatively and
postoperatively. Based on the preoperative measures, patients were categorized as
"high-functioning" (full-scale intelligence quotient [FSIQ] >=70; n = 48) and
"low-functioning" group (FSIQ <70; n = 40). Univariate and multivariate linear
regression analyses determined the clinical, electroencephalography (EEG), and
imaging factors associated with preoperative cognitive function as well as
postoperative cognitive change. RESULTS: Eighty-seven patients (98.8%) were
followed postoperatively for an average of 3.3 years, and 75 (85.2%) of them
achieved GS remission at the last hospital visit. Neuropsychological performance
was significantly improved after surgery in both groups. Multivariate linear
regression analysis showed that a smaller HH size (p = 0.002) and a smaller
number of antiepileptic drugs (p < 0.001) were preoperatively associated with
better neuropsychological performance. Multivariate linear regression analysis
showed that better postoperative improvement in cognition was associated with a
shorter duration of epilepsy (p = 0.03). SIGNIFICANCE: Cognitive impairment
related to epileptic encephalopathy may improve following SRT in substantial
proportions of HH patients. Reduced improvement in postoperative cognitive
function in patients with longer duration of epilepsy warrants further studies to
determine if earlier SRT provides a greater chance of postoperative cognitive
improvement in patients with HH.
PMID- 28703274
TI - Pterostilbene reduces oxidative stress, prevents hypertrophy and preserves
systolic function of right ventricle in cor pulmonale model.
AB - BACKGROUND AND PURPOSE: In cor pulmonale, the increased afterload imposed on the
right ventricle (RV) generates a maladaptive response, impairing the contractile
cardiac function. Oxidative mechanisms play an important role in the
pathophysiology and progression of this disease. The administration of
pterostilbene (PTS), a phytophenol with antioxidant potential, may represent a
therapeutic option. In the present study, we evaluated the effect of PTS
complexed with hydroxypropyl-beta-cyclodextrin (HPbetaCD) on hypertrophy,
contractile function and oxidative parameters in the RV of rats with pulmonary
hypertension, induced by the administration of monocrotaline (MCT). EXPERIMENTAL
APPROACH: The rats received daily doses of the PTS : HPbetaCD complex at 25, 50
or 100 mg.kg-1 , p.o., for 14 days. The diastolic function, E/A ratio, and
systolic function, shortening fraction, fractional area change (FAC) and
tricuspid annular plane systolic excursion (TAPSE) of the RV were determined by
echocardiography. KEY RESULTS: The PTS : HPbetaCD complex reduced the production
of NADPH oxidase-dependent superoxide anions and oxidative stress in the RV of
MCT-treated rats in a dose-dependent manner. At higher doses it prevented the
reduction in FAC and TAPSE in MCT-treated animals. CONCLUSIONS AND IMPLICATIONS:
The PTS : HPbetaCD complex prevented the maladaptative remodelling and protected
systolic function in the RV of rats with pulmonary hypertension. These
cardioprotective mechanisms may be related, in part, to the antioxidant potential
of PTS, favoured by the increased p.o. bioavailability promoted by the presence
of HPbetaCD in the complex.
PMID- 28703276
TI - Occurrence of sympatric charr groups, Salvelinus, Salmonidae, in the lakes of
Kamchatka: a legacy of the last glaciations.
AB - Six postglacial lakes were studied along both sides of the Kamchatka central
mountain range, Russia. Pairs of local morphotypes of species of Arctic charrs,
Salvelinus spp., have previously been described from the southernmost lakes while
the fish fauna of the four northernmost lakes was studied here for the first
time. Phenotypic data support the division of Kamchatkan lacustrine charrs into
two groups according to the number of gill rakers and pyloric caeca, as well as
snout-dorsal and snout-ventral distances (MANOVA, P < 0.001). These groups
respectively correspond to phenotypes commonly referred to as Salvelinus malma
and Salvelinus taranetzi. To clarify the identity of these groups, D-loop and
cytochrome b (cytb) region sequences were analysed. Haplotype network analysis of
mtDNA shows the salmonids inhabiting four lakes on the south and north are
phylogenetically close to either Beringian S. malma or to S. taranetzi from the
Chukotka and Kolyma River basins (the mean +/- s.e. pairwise per cent sequence
divergence is 0.006 +/- 0.001). Phenotype-genotype discordance suggests that
mitochondrial introgression between species has occurred in the two smallest
lakes (<0.5 km2 ) in the central part of the peninsula. Identical haplotypes of D
loop and cytb regions were found for the populations of S. taranetzi from the
most distant southern and northern lakes, indicating all lakes were colonized by
both species simultaneously after the last glacial maximum. Salvelinus taranetzi
may have colonized the Kamchatka peninsula from one or both of two different
source regions: the Arctic Beringia and the northern coast of the Okhotsk Sea.
PMID- 28703277
TI - miRNAs and ovarian cancer: An overview.
AB - Ovarian cancer (OC) is the sixth most common cancer in women globally. However,
even with the advances in detection and therapeutics it still represents the most
dangerous gynecologic malignancy in women of the industrialized countries. The
discovery of micro-RNAs (miRNA), a small noncoding RNA molecule targeting
multiple mRNAs and regulation of gene expression by triggering translation
repression and/or RNA degradation, has revealed the existence of a new array for
regulation of genes involved in cancer. This review summarizes the current
knowledge regarding the role of miRNAs expression in OC. It also provides
information about potential clinical relevance of circulating miRNAs for OC
diagnosis, prognosis, and therapeutics. The identification of functional targets
for miRNAs represents a major obstacle in our understanding of microRNA function
in OC, but significant progress is being made. The better understanding of the
role of microRNA expression in ovarian cancer may provide new array for the
detection, diagnosis, and therapy of the OC.
PMID- 28703278
TI - Reconstruction of 3D grain boundaries from rock thin sections, using an advanced
polarised-light microscopy method.
AB - Grain boundaries play a significant role in materials by initiating reactions and
collecting impurities. Here we present FAGO (Fabric Analyser Grain boundary
recOnstruction), a first step towards the automatic determination of three
dimensional (3D) grain boundary geometry using polarised light. The trace of the
grain boundaries from 2D rock thin sections are determined primarily from data
acquired using an automatic fabric analyser microscope and the FAME software
(fabric analyser-based microstructure evaluation; Peternell and colleagues and
Hammes and Peternell). Based on the Fabric Analyser G50's unique arrangement of
nine differently oriented light sources the retardation can be determined
independently for each light direction and at each pixel in the field of view.
FAGO combines these retardation datasets for each individual pixel together with
retardation profiles across grain boundaries, to determine the orientations of
the boundaries. The grain boundary traces are then broken up into segments of
equal orientation, using the profile-obtained orientation data. Finally, a 3D
grain boundary model is reconstructed. The data processing is almost fully
automatic using the MATLAB(r) environment. Only minor manual inputs are required.
PMID- 28703279
TI - Lactulose production by a thermostable glycoside hydrolase from the
hyperthermophilic archaeon Caldivirga maquilingensis IC-167.
AB - BACKGROUND: Lactulose has various uses in the food and pharmaceutical fields.
Thermostable enzymes have many advantages for industrial exploitation, including
high substrate solubilities as well as reduced risk of process contamination.
RESULTS: Enzymatic synthesis of lactulose employing a transgalactosylation
reaction by a recombinant thermostable glycoside hydrolase (GH1) from the
hyperthermophilic archaeon Caldivirga maquilingensis IC-167 was investigated. The
optimal pH for lactulose production was found to be 4.5, while the optimal
temperature was 85 degrees C, before it dropped moderately to 83% at 90 degrees
C. However, the relative activity for lactulose synthesis dropped sharply to 35%
at 95 degrees C. At optimal reaction conditions of 70% (w/w) initial sugar
substrates with molar ratio of lactose to fructose of 1:4, 15 U mL-1 enzyme
concentration and 85 degrees C, the time course reaction produced a maximum
lactulose concentration of 108 g L-1 at 4 h, corresponding to a lactulose yield
of 14% and 27 g L-1 h-1 productivity with 84% lactose conversion. The
transgalactosylation reaction for lactulose synthesis was greatly influenced by
the ratio of galactose donor to acceptor. CONCLUSION: This novel GH1 may be
useful for process applications owing to its high activity in very concentrated
substrate reaction media and promising thermostability. (c) 2017 Society of
Chemical Industry.
PMID- 28703280
TI - The OregonHeart Total Artificial Heart: Design and Performance on a Mock
Circulatory Loop.
AB - Widespread use of heart transplantation is limited by the scarcity of donor
organs. Total artificial heart (TAH) development has been pursued to address this
shortage, especially to treat patients who require biventricular support. We have
developed a novel TAH that utilizes a continuously spinning rotor that shuttles
between two positions to provide pulsatile, alternating blood flow to the
systemic and pulmonary circulations without artificial valves. Flow rates and
pressures generated by the TAH are controlled by adjusting rotor speed, cycle
frequency, and the proportion of each cycle spent pumping to either circulation.
To validate the design, a TAH prototype was placed in a mock circulatory loop
that simulates vascular resistance, pressure, and compliance in normal and
pathophysiologic conditions. At a systemic blood pressure of 120/80 mm Hg,
nominal TAH output was 7.4 L/min with instantaneous flows reaching 17 L/min.
Pulmonary artery, and left and right atrial pressures were all maintained within
normal ranges. To simulate implant into a patient with severe pulmonary
hypertension, the pulmonary vascular resistance of the mock loop was increased to
7.5 Wood units. By increasing pump speed to the pulmonary circulation, cardiac
output could be maintained at 7.4 L/min as mean pulmonary artery pressure
increased to 56 mm Hg while systemic blood pressures remained normal. This in
vitro testing of a novel, shuttling TAH demonstrated that cardiac output could be
maintained across a range of pathophysiologic conditions including pulmonary
hypertension. These experiments serve as a proof-of-concept for the design, which
has proceeded to in vivo testing.
PMID- 28703281
TI - Topotecan-loaded lipid nanoparticles as a viable tool for the topical treatment
of skin cancers.
AB - OBJECTIVES: This work aimed to evaluate semisolid formulations containing
topotecan (TPT) loaded nanostructured lipid carriers (NLC) for topical treatment
of skin cancers, as TPT is effective against a variety of tumours. A formulation
which increases TPT skin permeation would be extremely desirable. METHODS: TPT
NLC were prepared and incorporated in hydrogels with hydroxyethyl cellulose and
chitosan (TPT-NLC-HEC and TPT-NLC-Ch, respectively). Control formulations were
obtained by dispersing TPT in HEC and Ch hydrogels (TPT-HEC and TPT-Ch). KEY
FINDINGS: TPT-NLC-HEC and TPT-NLC-Ch showed to maintain the drug and nanoparticle
dispersions stable for up to 30 days. When nanoparticles were incorporated into
gels, TPT release was significantly decreased (P < 0.05). Still, TPT-NLC-HEC
increased 2.37 times permeation compared with TPT-HEC (11.9 and 5.0 MUg/cm2 ,
respectively). Cell culture experiments with B16F10 melanoma demonstrated that
nanoencapsulation significantly increased TPT cytotoxicity (P < 0.05). TPT-NLC
was more toxic than free TPT, with IC50 value of 5.74 MUg/ml, whereas free TPT
had an IC50 > 20 MUg/ml. As skin permeated values of TPT from developed
formulation (TPT-NLC) were superior to melanoma IC50, it can be extrapolated that
chemotherapeutic permeated amounts may be sufficient for a therapeutic effect.
CONCLUSIONS: TPT-NLC-HEC may be a valuable tool for the topical treatment of skin
cancers.
PMID- 28703282
TI - Structural insights into a secretory abundant heat-soluble protein from an
anhydrobiotic tardigrade, Ramazzottius varieornatus.
AB - Upon stopping metabolic processes, some tardigrades can undergo anhydrobiosis.
Secretory abundant heat-soluble (SAHS) proteins have been reported as candidates
for anhydrobiosis-related proteins in tardigrades, which seem to protect
extracellular components and/or secretory organelles. We determined structures of
a SAHS protein from Ramazzottius varieornatus (RvSAHS1), which is one of the
toughest tardigrades. RvSAHS1 shows a beta-barrel structure similar to fatty acid
binding proteins (FABPs), in which hydrophilic residues form peculiar hydrogen
bond networks, which would provide RvSAHS1 with better tolerance against
dehydration. We identified two putative ligand-binding sites: one that
superimposes on those of some FABPs and the other, unique to and conserved in
SAHS proteins. These results indicate that SAHS proteins constitute a new FABP
family.
PMID- 28703284
TI - Brentuximab vedotin in CD30+ cutaneous lymphoma: How do we treat, how shall we
treat? A review of the literature.
AB - Brentuximab vedotin is an antibody-drug conjugate that brings the antimicrotubule
agent monomethyl auristatin E into CD30-expressing cells. Some prior studies
demonstrated good efficacy in cutaneous lymphomas. The standard therapeutic
scheme is 1.8 mg kg-1 every 3 weeks. The background of this work is the fact that
cutaneous lymphoma has a different pathophysiology and a dynamic other than
systemic lymphomas. The objectives of this review were to get an overview of the
currently used therapeutic regimen, and to check whether dose reduction or
modified time intervals could be of benefit in a similar way with less toxicity.
Therefore, we conducted a systematic review of the literature indexed in PubMed
and the Cochrane Central Register of Controlled Trials up to April 2016. The
procedure was based on the Preferred Reporting Items for Systematic Reviews and
Meta-Analyses (PRISMA) criteria. The review showed that the currently used
therapeutic regimen is 1.8 mg kg-1 every 3 weeks. No publications of dose-finding
studies in CD30+ cutaneous T-cell lymphoma (CTCL) were found. Two cases of
patients, treated with a dose < 1.8 mg kg-1 , have been published. Brentuximab
vedotin seems to be a powerful treatment option in refractory CD30+ CTCL, and
there is a trend that dose reductions, as well as prolonged treatment intervals,
work without any loss of response and with fewer side-effects.
PMID- 28703283
TI - Wnt signalling pathways in chronic lymphocytic leukaemia and B-cell lymphomas.
AB - : In this review, we discuss the intricate roles of the Wnt signalling network in
the development and progression of mature B-cell-derived haematological
malignancies, with a focus on chronic lymphocytic leukaemia (CLL) and related B
cell lymphomas. We review the current literature and highlight the differences
between the beta-catenin-dependent and -independent branches of Wnt signalling.
Special attention is paid to the role of the non-canonical Wnt/planar cell
polarity (PCP) pathway, mediated by the Wnt-5-receptor tyrosine kinase-like
orphan receptor (ROR1)-Dishevelled signalling axis in CLL. This is mainly because
the Wnt/PCP co-receptor ROR1 was found to be overexpressed in CLL and the Wnt/PCP
pathway contributes to numerous aspects of CLL pathogenesis. We also discuss the
possibilities of therapeutically targeting the Wnt signalling pathways as an
approach to disrupt the crucial interaction between malignant cells and their
micro-environment. We also advocate the need for research in this direction for
other lymphomas, namely, diffuse large B-cell lymphoma, Hodgkin lymphoma, mantle
cell lymphoma, Burkitt lymphoma and follicular lymphoma where the Wnt signalling
pathway probably plays a similar role. LINKED ARTICLES: This article is part of a
themed section on WNT Signalling: Mechanisms and Therapeutic Opportunities. To
view the other articles in this section visit
http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.24/issuetoc.
PMID- 28703285
TI - Cervical mesonephric hyperplasia lacks KRAS/NRAS mutations.
PMID- 28703286
TI - Effect of quercetin on cadmium chloride-induced impairments in sexual behaviour
and steroidogenesis in male Wistar rats.
AB - Cadmium chloride (CdCl2 ) has been reported to cause reproductive toxicity in
male rats, mainly through oxidative stress. This study examined its effect on
sexual behaviour, as one of the mechanisms of reproductive dysfunction, as well
as the possible ameliorative effect of quercetin (QE) on same. Thirty male Wistar
rats (10 weeks old), weighing 270-300 g, were used for this study. They were
either orally administered 2% DMSO, CdCl2 (5 mg/kg b.w.), QE (20 mg/kg b.w.) or
CdCl2 +QE, once daily for 4 weeks, before sexual behavioural studies. The 5th
group received CdCl2 for 4 weeks and allowed 4-week recovery period, before
sexual behavioural test. Rats were sacrificed after sexual behavioural studies.
The blood, testis and penis were collected for biochemical assays. Cadmium
increased mount, intromission and ejaculatory latencies, but reduced their
frequencies, compared to control. Serum nitric oxide increased, while penile
cyclic guanosine monophosphate reduced in the CdCl2 -exposed rats, compared to
control. CdCl2 increased testicular cholesterol, but reduced 3beta-hydroxysteroid
dehydrogenase (3beta-HSD) and 17beta-HSD activities, and testosterone
concentration. QE better attenuated these negative changes compared to withdrawal
of CdCl2 treatment. In conclusion, CdCl2 suppressed steroidogenesis, penile
erection and sexual behaviour, with poor reversal following withdrawal, while QE
attenuated these effects.
PMID- 28703287
TI - Immune tolerance in transplantation.
PMID- 28703288
TI - A comparative proteomic analysis of blood serum for developmental stages in pigs.
AB - This study aimed to differentiate genes at developmental stages of pigs from 0 to
150 days of age, to build up a protein database and to find candidate genetic
markers for growth traits. The analysis of two-dimensional electrophoresis and
matrix-assisted laser-desorption/ionization mass spectrometry separated 252
protein segments. After successfully blasting the peptide sequences, the analysis
confirmed 37 differentially expressed proteins that increased from birth to 150
days of age (type A), whereas the type B proteins presented the inverse pattern.
The type C proteins included proteins that were expressed continuously throughout
the developmental periods. A total of 319 primer sets for 33 genes were designed
to find genetic variants using pooled DNA samples of Yorkshire pigs.
Amplification products for all primer sets produced approximately 20 000 clones
that were sequenced, and 48 candidate SNP sites were finalized for genotyping. A
total of 475 animals were used for high throughput genotyping analysis. Among
these, phenotype data of all 475 animals were collected for average daily gain,
backfat thickness and days to 90 kg, whereas feed conversion data were collected
for 300 animals and body measurement traits (starting weight, ending weight, body
length, wither height and chest depth) were collected for 209 animals.
Association analysis found significant statistical differences between the
animals having genotypes of 13 SNPs (g.78935883C>T, g.147629986C>T,
g.98266037T>C, g.214707340G>A, g.88350299C>T, g.17180956C>T, g.17181024C>T,
g.2350283A>G, g.138361311C>T, g.44996379C>T, g.44996247A>C, g.107715245C>T,
g.4149631C>T) for the various measured traits. The identified genetic
polymorphisms, of which one was novel (g.214707340G>A), may serve as candidate
molecular markers to change population means for the targeted growth traits.
PMID- 28703289
TI - Maresin 1 inhibits TNF-alpha-induced lipolysis and autophagy in 3T3-L1
adipocytes.
AB - Obesity is associated with high levels of pro-inflammatory cytokines such as
tumor necrosis factor-alpha (TNF-alpha), which promotes inflammation in adipose
tissue. The omega-3 PUFAs, and their derived lipid mediators, such as Maresin 1
(MaR1) have anti-inflammatory effects on adipose tissue. This study aimed to
analyze if MaR1 may counteract alterations induced by TNF-alpha on lipolysis and
autophagy in mature 3T3-L1 adipocytes. Our data revealed that MaR1 (1-100 nM)
inhibited the TNF-alpha-induced glycerol release after 48 hr, which may be
related to MaR1 ability of preventing the decrease in lipid droplet-coating
protein perilipin and G0/G1 Switch 2 protein expression. MaR1 also reversed the
decrease in total hormone sensitive lipase (total HSL), and the ratio of
phosphoHSL at Ser-565/total HSL, while preventing the increased ratio of
phosphoHSL at Ser-660/total HSL and phosphorylation of extracellular signal
regulated kinase 1/2 induced by TNF-alpha. Moreover, MaR1 counteracted the
cytokine-induced decrease of p62 protein, a key autophagy indicator, and also
prevented the induction of LC3II/LC3I, an important autophagosome formation
marker. Current data suggest that MaR1 may ameliorate TNF-alpha-induced
alterations on lipolysis and autophagy in adipocytes. This may also contribute to
the beneficial actions of MaR1 on adipose tissue and insulin sensitivity in
obesity.
PMID- 28703290
TI - The association between peri-operative acute risk change (ARC) and long-term
survival after cardiac surgery.
AB - Acute risk change has been described as the difference in calculated mortality
risk between the pre-operative and postoperative periods of cardiac surgery. We
aimed to assess whether this was associated with long-term survival after cardiac
surgery. We retrospectively analysed 22,570 cardiac surgical patients, with
minimum and maximum follow-up of 1.0 and 6.7 years. Acute risk change was
calculated as the arithmetic difference between pre- and postoperative mortality
risk. 'Rising risk' represented an increase in risk from pre- to postoperative
phase. The primary outcome was one-year mortality. Secondary outcomes included
mortality at 3 and 5 years and time to death. Univariable and multivariable
analyses were undertaken to examine the relationship between acute risk change
and outcomes. Rising risk was associated with higher mortality (5.6% vs. 3.5%, p
< 0.001). After adjusting for baseline risk, rising risk was independently
associated with increased 1-year mortality (OR 2.6, 95%CI 2.2-3.0, p < 0.001).
The association of rising risk with long-term survival was greatest in patients
with highest baseline risk. Cox regression confirmed rising risk was associated
with shorter time to death (HR 1.86, 1.68-2.05, p < 0.001). Acute risk change may
represent peri-operative clinical events in combination with unmeasured patient
risk and noise. Measuring risk change could potentially identify patterns of
events that may be amenable to investigation and intervention. Further work with
case review, and risk scoring with shared variables, may identify mechanisms,
including the interaction between miscalibration of risk and true differences in
peri-operative care.
PMID- 28703291
TI - The recent colonization of south Brazil by the Azores chromis Chromis limbata.
AB - The damselfish Chromis limbata is native to the Macaronesian Archipelagos
(Azores, Madeira and Canaries) and the western coast of Africa between Senegal
and Angola. During the austral summers of 2008 and 2009 the species was recorded
for the first time in the south-western Atlantic Ocean around Campeche and Xavier
Islands, in Florianopolis, Santa Catarina State, Brazil. Here, the progression of
C. limbata in southern Brazilian waters is described using visual counts and
genetic surveys and changes in the density of the native congener Chromis
multilineata were also investigated. Underwater visual censuses of both Chromis
species were carried out from 2009 to 2014. Chromis limbata tissue samples were
collected and the mtDNA control region was sequenced and compared with mtDNA
haplotypes from the natural range to confirm species identity, compare genetic
diversity and to infer connectivity between newly established Brazilian
populations. The Brazilian population of C. limbata increased significantly over
the past 5 years and the effect on C. multilineata is still an open question,
longer time-series data will be necessary to clarify possible interactions. The
molecular analyses confirmed species identity, revealed strong haplotype
connectivity among Brazilian study sites and showed a low genetic diversity in
Brazil when compared with the native populations, suggesting few individuals
started the invasion. Four hypotheses could explain this colonizing event: C.
limbata was released by aquarium fish keepers; larvae or juveniles were
transported via ship ballast water; the species has rafted alongside oil rigs;
they crossed the Atlantic Ocean through normal larval dispersal or naturally
rafting alongside drifting objects. The rafting hypotheses are favoured, but all
four possibilities are plausible and could have happened in combination.
PMID- 28703292
TI - A reassessment of explanations for discordant introgressions of mitochondrial and
nuclear genomes.
AB - Hybridization is increasingly recognized as a significant evolutionary process,
in particular because it can lead to introgression of genes from one species to
another. A striking pattern of discordance in the amount of introgression between
mitochondrial and nuclear markers exists such that substantial mitochondrial
introgression is often found in combination with no or little nuclear
introgression. Multiple mechanisms have been proposed to explain this
discordance, including positive selection for introgressing mitochondrial
variants, several types of sex-biases, drift, negative selection against
introgression in the nuclear genome, and spatial expansion. Most of these
hypotheses are verbal, and have not been quantitatively evaluated so far. We use
individual-based, multilocus, computer simulations of secondary contact under a
wide range of demographic and genetic scenarios to evaluate the ability of the
different mechanisms to produce discordant introgression. Sex-biases and spatial
expansions fail to produce substantial mito-nuclear discordance. Drift and
nuclear selection can produce strong discordance, but only under a limited range
of conditions. In contrast, selection on the mitochondrial genome produces strong
discordance, particularly when dispersal rates are low. However, commonly used
statistical tests have little power to detect this selection. Altogether, these
results dismiss several popular hypotheses, and provide support for adaptive
mitochondrial introgression.
PMID- 28703294
TI - Seed production and predation in a changing climate: new roles for resource and
seed predator feedback?
AB - Climate change may cause changes in the dynamics of populations beyond
comparatively simple directional effects. To better understand complex effects on
dynamics requires long-term studies of populations that experience changes in
climatic conditions. We study the dynamics of a seed-production-seed-predation
system, consisting of a perennial herb and its two seed predatory insects, over a
40-yr period during which climate change has caused the annual growing season to
increase by 20 d. During this period, plant patches have increased almost
threefold in size and seed production has slipped into a pattern of alternate
high and low years with a higher variance than in the beginning of the period. We
find that seed production is associated with precipitation of the present summer
and a non-linear feedback from seed production of the previous year. When
previous year's seed production is low, weather forcing and unexplained noise
determine the extent of seed production. When previous seed production is high,
depleted resources limit seed production. Resource depletion happened frequently
in the latter parts of the study but rarely in the beginning. The changing
patterns of seed production in turn affect the dynamics of seed predation, which
is dominated by one of the seed predators. Its dynamics are strongly linked to
seed density fluctuations, but its population growth rate is satiated when
resource fluctuations become too large. In the latter part of the study period,
when seed fluctuations were alternating between years of high and low density,
satiation was common and there was a large increase in surviving seeds in good
years. Our study illustrates that a changing climate can fundamentally influence
patterns of long-term dynamics at multiple trophic levels.
PMID- 28703293
TI - BMP- and TGFbeta-signaling regulate the formation of Muller glia-derived
progenitor cells in the avian retina.
AB - Muller glia-derived progenitor cells (MGPCs) have the capability to regenerate
neurons in the retinas of different vertebrate orders. The formation of MGPCs is
regulated by a network of cell-signaling pathways. The purpose of this study was
to investigate how BMP/Smad1/5/8- and TGFbeta/Smad2/3-signaling are coordinated
to influence the formation of MGPCs in the chick model system. We find that
pSmad1/5/8 is selectively up-regulated in the nuclei of Muller glia following
treatment with BMP4, FGF2, or NMDA-induced damage, and this up-regulation is
blocked by a dorsomorphin analogue DMH1. By comparison, Smad2/3 is found in the
nuclei of Muller glia in untreated retinas, and becomes localized to the
cytoplasm following NMDA- or FGF2-treatment. These findings suggest a decrease in
TGFbeta- and increase in BMP-signaling when MGPCs are known to form. In both NMDA
damaged and FGF2-treated retinas, inhibition of BMP-signaling suppressed the
proliferation of MGPCs, whereas inhibition of TGFbeta-signaling stimulated the
proliferation of MGPCs. Consistent with these findings, TGFbeta2 suppressed the
formation of MGPCs in NMDA-damaged retinas. Our findings indicate that
BMP/TGFbeta/Smad-signaling is recruited into the network of signaling pathways
that controls the formation of proliferating MGPCs. We conclude that signaling
through BMP4/Smad1/5/8 promotes the formation of MGPCs, whereas signaling through
TGFbeta/Smad2/3 suppresses the formation of MGPCs.
PMID- 28703295
TI - Expanding career pathways in conservation science.
PMID- 28703296
TI - Correlation between TLR2, TLR3, TLR4, and TLR9 polymorphisms and susceptibility
to and prognosis of severe hepatitis among the newborns.
AB - BACKGROUND: This study was aimed to explore how toll-like receptor 2 (TLR2),
TLR3, TLR4 and TLR9 influenced the risk and prognosis of severe hepatitis among
the Chinese newborns. METHODS: Altogether 135 newborns diagnosed with severe
hepatitis and 140 healthy newborns were included in this study. Totally 12 single
nucleotide polymorphisms (SNPs) within TLR2, TLR3, TLR4, and TLR9 were chosen and
genotyped by polymerase chain reaction-restriction fragment length polymorphism
(PCR-RFLP). Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated
using the logistic regression. The univariate and multivariate analyses were used
to analyze independent factors for prognosis of severe hepatitis among the
Chinese newborns. RESULTS: The SNPs within TLR2 [ie, rs1898830 (A>G) and
rs3804100 (T>C)], TLR3 [ie, rs1879026 (G>T)], TLR4 [ie, rs2149356 (T>G)], and
TLR9 [ie, rs187084 (T>C), rs352139 (A>G), and rs352140 (C>T)] were significantly
associated with modified risk of neonatal severe hepatitis (all P<.05).
Furthermore, rs1898830, rs1879026, rs187084 and rs352139 were also demonstrated
to modulate the prognosis [ie, aspartate aminotransferase (AST)/alanine
transaminase (ALT)>1.5] of newborns with severe hepatitis (all P<.05).
Interestingly, the haplotype A-C-G-G-C-A-T were associated with higher
susceptibility to neonatal severe hepatitis, and the newborns carrying haplotype
A-C-G-G-C-A-T appeared to be correlated with more favorable prognosis (all
P<.05). CONCLUSIONS: Certain SNPs and haplotypes within TLR2, TLR3, TLR4, and
TLR9 can be considered as the potentially treatment targets for neonatal severe
hepatitis.
PMID- 28703297
TI - Neither eosinophils nor neutrophils require ATG5-dependent autophagy for
extracellular DNA trap formation.
AB - The importance of extracellular traps (ETs) in innate immunity is well
established, but the molecular mechanisms responsible for their formation remain
unclear and in scientific dispute. ETs have been defined as extracellular DNA
scaffolds associated with the granule proteins of eosinophils or neutrophils.
They are capable of killing bacteria extracellularly. Based mainly on results
with phosphoinositide 3-kinase (PI3K) inhibitors such as 3-methyladenine (3-MA)
and wortmannin, which are commonly used to inhibit autophagy, several groups have
reported that autophagy is required for neutrophil extracellular trap (NET)
formation. We decided to investigate this apparent dependence on autophagy for ET
release and generated genetically modified mice that lack, specifically in
eosinophils or neutrophils, autophagy-related 5 (Atg5), a gene encoding a protein
essential for autophagosome formation. Interestingly, neither eosinophils nor
neutrophils from Atg5-deficient mice exhibited abnormalities in ET formation upon
physiological activation or exposure to low concentrations of PMA, although we
could confirm that human and mouse eosinophils and neutrophils, after pre
treatment with inhibitors of class III PI3K, show a block both in reactive oxygen
species (ROS) production and in ET formation. The so-called late autophagy
inhibitors bafilomycin A1 and chloroquine, on the other hand, were without
effect. These data indicate that ET formation occurs independently of autophagy
and that the inhibition of ROS production and ET formation in the presence of 3
MA and wortmannin is probably owing to their additional ability to block the
class I PI3Ks, which are involved in signalling cascades initiated by triggers of
ET formation.
PMID- 28703298
TI - Introduction to anatomy on Wikipedia.
AB - Wikipedia (www.wikipedia.com) is the largest encyclopaedia in existence. Of over
five million English-language articles, about 6000 relate to Anatomy, which are
viewed roughly 30 million times monthly. No work parallels the amount of
attention, scope or interdisciplinary layout of Wikipedia, and it offers a unique
opportunity to improve the anatomical literacy of the masses. Anatomy on
Wikipedia is introduced from an editor's perspective. Article contributors,
content, layout and accuracy are discussed, with a view to demystifying editing
for anatomy professionals. A final request for edits or on-site feedback from
anatomy professionals is made.
PMID- 28703299
TI - Can an eel be a flatfish? Observations on enigmatic asymmetrical heterenchelyids
from the Guinea coast of West Africa.
AB - Morphological asymmetry is described in the heterenchelyid mud eel Pythonichthys
cf. macrurus from inshore coastal waters of Guinea, West Africa. The intensity of
asymmetry differs between two examined specimens, with the more extreme case
exhibiting strong asymmetry in both external and internal features, including
unilateral depigmentation, reductive degeneration and embedding of a blind-side
eye, skewed jaws with reduced dentition and tooth loss. The extent and nature of
asymmetry suggests that this individual probably lived primarily on its left
lateral side, not unlike sinistral pleuronectiform flatfishes.
PMID- 28703300
TI - A point-based prediction model for cardiovascular risk in orthotopic liver
transplantation: The CAR-OLT score.
AB - : Cardiovascular disease (CVD) complications are important causes of morbidity
and mortality after orthotopic liver transplantation (OLT). There is currently no
preoperative risk-assessment tool that allows physicians to estimate the risk for
CVD events following OLT. We sought to develop a point-based prediction model
(risk score) for CVD complications after OLT, the Cardiovascular Risk in
Orthotopic Liver Transplantation risk score, among a cohort of 1,024 consecutive
patients aged 18-75 years who underwent first OLT in a tertiary-care teaching
hospital (2002-2011). The main outcome measures were major 1-year CVD
complications, defined as death from a CVD cause or hospitalization for a major
CVD event (myocardial infarction, revascularization, heart failure, atrial
fibrillation, cardiac arrest, pulmonary embolism, and/or stroke). The bootstrap
method yielded bias-corrected 95% confidence intervals for the regression
coefficients of the final model. Among 1,024 first OLT recipients, major CVD
complications occurred in 329 (32.1%). Variables selected for inclusion in the
model (using model optimization strategies) included preoperative recipient age,
sex, race, employment status, education status, history of hepatocellular
carcinoma, diabetes, heart failure, atrial fibrillation, pulmonary or systemic
hypertension, and respiratory failure. The discriminative performance of the
point-based score (C statistic = 0.78, bias-corrected C statistic = 0.77) was
superior to other published risk models for postoperative CVD morbidity and
mortality, and it had appropriate calibration (Hosmer-Lemeshow P = 0.33).
CONCLUSION: The point-based risk score can identify patients at risk for CVD
complications after OLT surgery (available at www.carolt.us); this score may be
useful for identification of candidates for further risk stratification or other
management strategies to improve CVD outcomes after OLT. (Hepatology 2017;66:1968
1979).
PMID- 28703302
TI - Control of Helical Chirality of Ferrocene-Dipeptide Conjugates by the Secondary
Structure of Dipeptide Chains.
AB - Controlling helical chirality and creating protein secondary structures in
cyclic/acyclic ferrocene-dipeptide bioorganometallic conjugates were achieved by
adjusting the conformational flexibility of the dipeptide chains. In systems
reported to date, the helical chirality of a conjugate was determined by the
absolute configuration of the adjacent amino acid reside. In contrast, it was
possible to induce both M- and P-helical chirality, even when the configuration
of the adjacent amino acid was the same. It is particularly interesting to note
that M-helical chirality was produced in a cyclic ferrocene-dipeptide conjugate
composed of the l-Ala-d-Pro-cystamine-d-Pro-l-Ala dipeptide sequence (1), in
which a type II beta-turn-like secondary structure was established.
PMID- 28703301
TI - The xenoestrogens biphenol-A and nonylphenol differentially regulate
metalloprotease-mediated shedding of EGFR ligands.
AB - The xenoestrogens bisphenol-A (BPA) and nonylphenol (NP) are endocrine disruptors
used in the plastic polymer industry to manufacture different products for human
use. Previous studies have suggested a role of these compounds in the shedding of
signaling molecules, such as tumor necrosis factor alpha (TNF-alpha). The aim of
this work was to evaluate the effect of BPA and NP on the sheddase ADAM17 and its
newly discovered regulators iRhom1 and iRhom2 in the release of EGFR-ligands. We
report that BPA and NP can stimulate the release of the ADAM17-substrates HB-EGF
and TGF-alpha. In cells lacking ADAM17 (Adam17-/- mEFs) BPA-stimulated release of
HB-EGF, but not TGF-alpha, was strongly reduced, whereas NP-stimulated shedding
of HB-EGF and TGF-alpha was completely abolished. Inactivation of both ADAM17 and
the related ADAM10 (Adam10/17-/- mEFs) completely prevented the release of these
substrates. In the absence of iRhom1, BPA- or NP-stimulated release of HB-EGF or
TGF-alpha was comparable to wild-type control mEFs, conversely the BPA-induced
release of HB-EGF was abolished in iRhom2-/- mEFs. The defect in shedding of HB
EGF in iRhom2-/- mEF cells could be rescued by overexpressing iRhom2.
Interestingly, the NP-stimulated release of HB-EGF was not affected by the
absence of iRhom2, suggesting that NP could potentially activate both ADAM10 and
ADAM17. We tested this hypothesis using betacellulin (BTC), an EGFR-ligand that
is a substrate for ADAM10. We found that NP, but not BPA stimulated the release
of BTC in Adam17-/- , iRhom2-/- , or iRhom1/2-/- , but not in Adam10/17-/- cells.
Taken together, our results suggest that BPA and NP stimulate the release of EGFR
ligands by differentially activating ADAM17 or ADAM10. The identification of
specific effects of these endocrine disruptors on ADAM10 and ADAM17 will help to
provide a better understanding of their roles in cell signaling and
proinflammatory processes, and provide new potential targets for treatment of
reproductive or inflammatory diseases such as asthma or breast cancer that are
promoted by xenoestrogens.
PMID- 28703303
TI - Terminally Truncated Isopenicillin N Synthase Generates a Dithioester Product:
Evidence for a Thioaldehyde Intermediate during Catalysis and a New Mode of
Reaction for Non-Heme Iron Oxidases.
AB - Isopenicillin N synthase (IPNS) catalyses the four-electron oxidation of a
tripeptide, l-delta-(alpha-aminoadipoyl)-l-cysteinyl-d-valine (ACV), to give
isopenicillin N (IPN), the first-formed beta-lactam in penicillin and
cephalosporin biosynthesis. IPNS catalysis is dependent upon an iron(II) cofactor
and oxygen as a co-substrate. In the absence of substrate, the carbonyl oxygen of
the side-chain amide of the penultimate residue, Gln330, co-ordinates to the
active-site metal iron. Substrate binding ablates the interaction between Gln330
and the metal, triggering rearrangement of seven C-terminal residues, which move
to take up a conformation that extends the final alpha-helix and encloses ACV in
the active site. Mutagenesis studies are reported, which probe the role of the C
terminal and other aspects of the substrate binding pocket in IPNS. The
hydrophobic nature of amino acid side-chains around the ACV binding pocket is
important in catalysis. Deletion of seven C-terminal residues exposes the active
site and leads to formation of a new type of thiol oxidation product. The
isolated product is shown by LC-MS and NMR analyses to be the ene-thiol tautomer
of a dithioester, made up from two molecules of ACV linked between the thiol
sulfur of one tripeptide and the oxidised cysteinyl beta-carbon of the other. A
mechanism for its formation is proposed, supported by an X-ray crystal structure,
which shows the substrate ACV bound at the active site, its cysteinyl beta-carbon
exposed to attack by a second molecule of substrate, adjacent. Formation of this
product constitutes a new mode of reaction for IPNS and non-heme iron oxidases in
general.
PMID- 28703304
TI - Assessing the influence of media composition and ionic strength on drug release
from commercial immediate-release and enteric-coated aspirin tablets.
AB - OBJECTIVES: The objective of this test series was to elucidate the importance of
selecting the right media composition for a biopredictive in-vitro dissolution
screening of enteric-coated dosage forms. METHODS: Drug release from immediate
release (IR) and enteric-coated (EC) aspirin formulations was assessed in
phosphate-based and bicarbonate-based media with different pH, electrolyte
composition and ionic strength. KEY FINDINGS: Drug release from aspirin IR
tablets was unaffected by media composition. In contrast, drug release from EC
aspirin formulations was affected by buffer species and ionic strength. In all
media, drug release increased with increasing ionic strength, but in bicarbonate
based buffers was delayed when compared with that in phosphate-based buffers.
Interestingly, the cation species in the dissolution medium had also a clear
impact on drug release. Drug release profiles obtained in Blank CarbSIF, a new
medium simulating pH and average ionic composition of small intestinal fluid,
were different from those obtained in all other buffer compositions studied.
CONCLUSIONS: Results from this study in which the impact of various media
parameters on drug release of EC aspirin formulations was systematically screened
clearly show that when developing predictive dissolution tests, it is important
to simulate the ionic composition of intraluminal fluids as closely as possible.
PMID- 28703305
TI - Use of multicriteria decision analysis for assessing the benefit and risk of over
the-counter analgesics.
AB - OBJECTIVES: To test the ability of a multicriteria decision analysis (MCDA) model
to incorporate disparate data sources of varying quality along with clinical
judgement in a benefit-risk assessment of six well-known pain-relief drugs.
METHODS: Six over-the-counter (OTC) analgesics were evaluated against three
favourable effects and eight unfavourable effects by seven experts who specialise
in the relief of pain, two in a 2-day facilitated workshop whose input data and
judgements were later peer-reviewed by five additional experts. KEY FINDINGS:
Ibuprofen salts and solubilised emerged with the best benefit-risk profile,
followed by naproxen, ibuprofen acid, diclofenac, paracetamol and aspirin.
CONCLUSIONS: Multicriteria decision analysis enabled participants to evaluate the
OTC analgesics against a range of favourable and unfavourable effects in a group
setting that enabled all issues to be openly aired and debated. The model was
easily communicated and understood by the peer reviewers, so the model should be
comprehensible to physicians, pharmacists and other health professionals.
PMID- 28703306
TI - Comparison of the topical FK506 and clobetasol propionate as first-line therapy
in the treatment of early alopecia areata.
PMID- 28703307
TI - Evidence of Atlantic salmon Salmo salar fry movement between fresh water and a
brackish environment.
AB - This study reports descent of Atlantic salmon Salmo salar fry from their natal
streams to brackish waters of the Baltic Sea and their use of this environment as
an alternative rearing habitat before ascending back to freshwater streams. To
the authors' knowledge, residency in a brackish environment has not previously
been demonstrated in S. salar fry. Recruitment success and evolutionary
significance of this alternative life-history strategy are presently not known.
PMID- 28703308
TI - Odors generated from the Maillard reaction affect autonomic nervous activity and
decrease blood pressure through the olfactory system.
AB - BACKGROUND: Systolic blood pressure (SBP) of rats decreases significantly
following exposure to the odor generated from the Maillard reaction of protein
digests with xylose. This study identified active odorants that affect blood
pressure and demonstrated the mechanism of action. RESULTS: Among the four potent
odorants that contribute most to the odor of the Maillard reaction sample, 2,5
dimethyl-4-hydroxy-3(2H)-furanone (DMHF) and 5-methyl-2-pyrazinemethanol (MPM)
decreased SBP significantly. The earliest decrease in blood pressure was observed
5 min after exposure to DMHF. Application of zinc sulfate to the nasal cavity
eliminated the effect. Furthermore, gastric vagal (parasympathetic) nerve
activity was elevated and renal sympathetic nerve activity was lowered after
exposure to DMHF. CONCLUSION: It is indicated that DMHF affects blood pressure
through the olfactory system, and the mechanism for the effect of DMHF on blood
pressure involves the autonomic nervous system. (c) 2017 Society of Chemical
Industry.
PMID- 28703309
TI - Micro in size but not in function-microRNAs in axonal survival and regeneration.
PMID- 28703312
TI - Violence exposure is associated with adolescents' same- and next-day mental
health symptoms.
AB - BACKGROUND: Young people exposed to violence are at increased risk for mental
health and behavioral problems. However, very little is known about the
immediate, or same-day, associations between violence exposure and adolescents'
mental health symptoms or whether daily symptom or behavioral reactivity marks
future problems. METHODS: Young adolescents were assessed three times a day for
30 consecutive days using mobile-phone-based Ecological Momentary Assessment
(EMA) (N = 151 adolescents). Over 12,500 assessments and 4,329 person days were
obtained via the EMA. Adolescents were recruited from low-income neighborhoods
based on parent-reported risk for externalizing symptoms. Mental health symptoms
were assessed via parent and child report at baseline, multiple times per day via
EMA assessments of the adolescents, and again 18 months later when 93% of the
adolescents were reinterviewed. RESULTS: Results from multilevel models
illustrated that young adolescents were more likely to experience symptoms of
anger (OR = 1.74, CI: 1.31-2.30), depression (OR = 1.66, CI: 1.26-2.19), and
conduct problems (OR = 2.63, CI: 1.71-4.04) on days that they were exposed versus
not exposed to violence. Increases in depressive symptoms were also observed on
days following violence exposure (OR = 1.46, CI: 1.09-1.97). Adolescents with the
highest levels of violence exposure across the 30-day EMA were less behaviorally
reactive to violence exposures in daily life, and heightened behavioral
reactivity predicted increased risk for substance use across early adolescence.
CONCLUSIONS: Findings support the need to focus on both the immediate and long
term associations between violence exposure and adolescents' mental health and
behavior. Results also suggest that heightened behavioral reactivity during early
adolescence may signal emerging substance use problems.
PMID- 28703313
TI - Mesenchymal stem cells: A new platform for targeting suicide genes in cancer.
AB - One of the important strategies for the treatment of cancer is gene therapy which
has the potential to exclusively eradicate malignant cells, without any damage to
the normal tissues. Gene-directed enzyme prodrug therapy (GDEPT) is a two-step
gene therapy approach, where a suicide gene is directed to tumor cells. The gene
encodes an enzyme that expressed intracellularly where it is able to convert a
prodrug into cytotoxic metabolites. Various delivery systems have been developed
to achieve the appropriate levels of tumor restricted expression of
chemotherapeutic drugs. Nowadays, mesenchymal stem cells (MSCs) have been drawing
great attention as cellular vehicles for gene delivery systems. Inherent
characteristics of MSCs make them particularly attractive gene therapy tools in
cell therapy. They have been used largely for their remarkable homing property
toward tumor sites and availability from many different adult tissues and show
anti-inflammatory actions in some cases. They do not stimulate proliferative
responses of lymphocytes, suggests that MSCs have low immunogenicity and could
avoid immune rejection. This review summarizes the current state of knowledge
about genetically modified MSCs that enable to co-transduce a variety of
therapeutic agents including suicide genes (i.e., cytosine deaminase, thymidine
kinase) in order to exert potent anti-carcinogenesis against various tumors
growth. Moreover, we highlighted the role of exosomes released from MSCs as new
therapeutic platform for targeting various therapeutic agents.
PMID- 28703311
TI - Mechanisms and prevention of UV-induced melanoma.
AB - Melanoma is the deadliest form of skin cancer and its incidence is rising,
creating a costly and significant clinical problem. Exposure to ultraviolet (UV)
radiation, namely UVA (315-400 nm) and UVB (280-315 nm), is a major risk factor
for melanoma development. Cumulative UV radiation exposure from sunlight or
tanning beds contributes to UV-induced DNA damage, oxidative stress, and
inflammation in the skin. A number of factors, including hair color, skin type,
genetic background, location, and history of tanning, determine the skin's
response to UV radiation. In melanocytes, dysregulation of this UV radiation
response can lead to melanoma. Given the complex origins of melanoma, it is
difficult to develop curative therapies and universally effective preventative
strategies. Here, we describe and discuss the mechanisms of UV-induced skin
damage responsible for inducing melanomagenesis, and explore options for
therapeutic and preventative interventions.
PMID- 28703314
TI - Stephanine from Stephania venosa (Blume) Spreng Showed Effective Antiplasmodial
and Anticancer Activities, the Latter by Inducing Apoptosis through the Reverse
of Mitotic Exit.
AB - Extracts from the tubers of Stephania venosa (Blum) Spreng growing in Vietnam
significantly inhibited cell proliferation against a number of cancer cells
including HeLa, MDA-MB231 and MCF-7 cells. A bioassay-guided fractionation led to
the isolation of four aporphine and one tetrahydroprotoberberine alkaloids:
dehydrocrebanine 1, tetrahydropalmatine 2, stephanine 3, crebanine 4 and O
methylbulbocapnine 5. The characterization of these compounds was based on MS,
NMR and published data. A study by structure-bioactivity relationship on these
isolates showed that stephanine is the most active compound. Cell biological
studies showed that stephanine induces the reverse of mitotic exit, eventually
leading to cell death by apoptosis. This data suggests that stephanine has a
unique mode of cell-killing activity against cancer cells, which is seldom
observed with known synthetic compounds. In addition to its anticancer property,
our data from an in vitro study showed that S. venosa also possesses effective
antiplasmodial activity and stephanine was also the most interesting compound but
is the most cytotoxic with the lowest selectivity index. Copyright (c) 2017 Her
Majesty the Queen in Right of Canada Phytotherapy Research StartCopTextCopyright
(c) 2017 John Wiley & Sons, Ltd.
PMID- 28703315
TI - Using whole-exome sequencing to investigate the genetic bases of lysosomal
storage diseases of unknown etiology.
AB - Lysosomes are membrane-bound, acidic eukaryotic cellular organelles that play
important roles in the degradation of macromolecules. Mutations that cause the
loss of lysosomal protein function can lead to a group of disorders categorized
as the lysosomal storage diseases (LSDs). Suspicion of LSD is frequently based on
clinical and pathologic findings, but in some cases, the underlying genetic and
biochemical defects remain unknown. Here, we performed whole-exome sequencing
(WES) on 14 suspected LSD cases to evaluate the feasibility of using WES for
identifying causal mutations. By examining 2,157 candidate genes potentially
associated with lysosomal function, we identified eight variants in five genes as
candidate disease-causing variants in four individuals. These included both known
and novel mutations. Variants were corroborated by targeted sequencing and, when
possible, functional assays. In addition, we identified nonsense mutations in two
individuals in genes that are not known to have lysosomal function. However,
mutations in these genes could have resulted in phenotypes that were diagnosed as
LSDs. This study demonstrates that WES can be used to identify causal mutations
in suspected LSD cases. We also demonstrate cases where a confounding clinical
phenotype may potentially reflect more than one lysosomal protein defect.
PMID- 28703316
TI - The Effect of Renal Impairment on the Pharmacokinetics and Pharmacodynamics of
Ertugliflozin in Subjects With Type 2 Diabetes Mellitus.
AB - Ertugliflozin is a highly selective and potent inhibitor of the sodium-glucose
cotransporter 2 in development for the treatment of type 2 diabetes mellitus. The
glycemic efficacy of sodium-glucose cotransporter 2 inhibitors such as
ertugliflozin depends on glucose filtration through the kidney. This phase 1,
open-label study evaluated the effect of renal impairment on the
pharmacokinetics, pharmacodynamics, and tolerability of ertugliflozin (15 mg) in
type 2 diabetes mellitus and healthy subjects with normal renal function
(estimated glomerular filtration rate not normalized for body surface area >=90
mL/min) and type 2 diabetes mellitus subjects with mild (60-89 mL/min), moderate
(30-59 mL/min), or severe (<30 mL/min) renal impairment (n = 36). Blood and urine
samples were collected predose and over 96 hours postdose for pharmacokinetic
evaluation and measurement of urinary glucose excretion over 24 hours. Log-linear
regression analyses indicated predicted mean area under the concentration-time
curve values for mild, moderate, and severe renal function groups that were <=70%
higher relative to subjects with normal renal function. Generally consistent
results were obtained with categorical analysis based on analysis of variance.
The increase in ertugliflozin exposure in subjects with renal impairment is not
expected to be clinically meaningful. Regression analysis of change from baseline
in urinary glucose excretion over 24 hours vs estimated glomerular filtration
rate showed a decrease in urinary glucose excretion with declining renal
function. A single 15-mg dose of ertugliflozin was well tolerated in all groups.
PMID- 28703317
TI - Organic meat quality of dual purpose young bulls supplemented with pea (Pisum
sativum L.) or soybean.
AB - BACKGROUND: One of the main constraints established by organic legislation that
limits the development of the rearing of young bulls is the ban on the use of
genetically modified organisms (GMO). Most of the worldwide cultivated soybean is
GMO, therefore the use of alternative protein sources should be evaluated. In
this study, the effect of dietary substitution of soybean with pea (Pisum sativum
L.) on carcass characteristics and meat quality of dual purpose young bulls
reared following the organic method was investigated. RESULTS: Twenty-four young
bulls of Rendena breed were randomly assigned to two diet treatments differing in
protein supplement (soybean (SB) or field pea (FP)). Carcass characteristics and
meat chemical composition, colour, cooking loss and Warner-Bratzler shear force
did not differ between groups. Regarding meat fatty acid composition, SB showed
higher concentrations of C18:0 and C18:1 t and lower C16:1n-9c, C14:0, C17:1n-9c
and C18:1n-9c than FP. In descriptive sensory analysis, trained judges were not
able to differentiate meats from SB and FP, which also had similar overall liking
expressed by consumers. CONCLUSION: The results of this study indicate that FP
can replace SB in the diet of dual purpose young bulls with only a minor
influence on fatty acid composition and no effect on carcass characteristics and
meat quality. (c) 2017 Society of Chemical Industry.
PMID- 28703318
TI - Fourier transform (FT)-artifacts and power-function resolution filter in Fourier
transform mass spectrometry.
AB - RATIONALE: Peak picking algorithms in mass spectrometry face the challenge of
picking the correct signals from a mass spectrum. In some cases signal wiggles
(side lobes) are also chosen in the produced mass list as if they were real
signals. Constraints which are defined in such algorithms do not always guarantee
wiggle-free accurate mass list generation out of raw mass spectra. This problem
intensifies with acquisitions, which are accompanied by longer transients. Thus,
the problem represents a contemporary issue, which propagates with modern high
memory digitizers and exists in both MS and MS/MS spectra. METHODS: A solariX
FTMS mass spectrometer with an Infinity ICR cell (Bruker Daltonics, Bremen,
Germany) coupled to a 12 Tesla magnet (Magnex, UK) was used for the experimental
study. Time-domain transients of several different data point lengths 512k, 1M,
2M, 4M, 8M were obtained and were Fourier-transformed to obtain frequency spectra
which show the effect of the transient truncation on sinc wiggle developments in
FT-ICR-MS. MATLAB simulations were also performed to investigate the origin of
the Fourier transform (FT)-artifacts. RESULTS: A new filter has been developed to
identify and remove FT-artifacts (sinc side lobes) from both frequency and mass
spectra. The newly developed filter is based on distinguishing between the FWHM
of the correct frequency/mass signals and the FWHM of their corresponding
wiggles. The filter draws a reliable confidence limit of resolution range, within
which a correct frequency/mass signal is identified. The filter is applicable
over a wide mass range of metabolic interest (100-1200 amu). CONCLUSIONS: The
origin of FT-artifacts due to time-domain transient truncations was thoroughly
investigated both experimentally and by simulations in this study. A new solution
for this problem with automatic recognition and elimination of these FT-artifacts
(side lobes/wiggles) is provided, which is independent of any intensity
thresholds, magnetic field strengths and time-domain transient lengths.
PMID- 28703320
TI - 5-aminolaevulinic acid patch-photodynamic therapy in the treatment of actinic
cheilitis.
AB - BACKGROUND: Actinic cheilitis (AC) is a common disease caused by chronic
ultraviolet exposure. OBJECTIVE: Alacare is a self-adhesive, skin coloured 5
aminolaevulinic acid (ALA) patch that has been developed for the treatment of
mild to moderate actinic keratosis (AK). Considering the good results in the
treatment of AK, the standardized delivery of ALA and the simple application
Alacare patch- photodynamic therapy (PDT) appears as an interesting treatment
option for AC. METHODS: We retrospectively assessed the efficacy, tolerability
and cosmetic outcome of Alacare patch-PDT in eleven patients with AC. After
occlusion with the Alacare patches for 4 hours, the AC lesions were illuminated
with narrowband red light and a dose of 37 J/cm2 . All patients were clinically
assessed for efficacy, side effects and cosmetic outcome at 3, 6, 9 and 12 months
after treatment. RESULTS: Complete clinical response at the 3-month follow-up was
achieved in eight of 11 patients (72,7%) and 12 of 15 AC lesions (80,0%),
respectively. Up to the final 12-month follow-up, a recurrence was observed in
two lesions. The complete clinical cure rate at 1 year after Alacare patch-PDT,
thus, was 66,6% (10/15 lesions). The cosmetic outcome of the treatment was
excellent in all cases. CONCLUSION: Alacare patch-PDT was found to have
substantial efficacy in the treatment of mild to moderate AC. Given its ease of
use, absence of long-term side effects and the excellent cosmetic results Alacare
patch-PDT might be considered as a promising new treatment option for the
management of AC.
PMID- 28703319
TI - Brain carnitine deficiency causes nonsyndromic autism with an extreme male bias:
A hypothesis.
AB - Could 10-20% of autism be prevented? We hypothesize that nonsyndromic or
"essential" autism involves extreme male bias in infants who are genetically
normal, but they develop deficiency of carnitine and perhaps other nutrients in
the brain causing autism that may be amenable to early reversal and prevention.
That brain carnitine deficiency might cause autism is suggested by reports of
severe carnitine deficiency in autism and by evidence that TMLHE deficiency - a
defect in carnitine biosynthesis - is a risk factor for autism. A gene on the X
chromosome (SLC6A14) likely escapes random X-inactivation (a mixed epigenetic and
genetic regulation) and could limit carnitine transport across the blood-brain
barrier in boys compared to girls. A mixed, common gene variant-environment
hypothesis is proposed with diet, minor illnesses, microbiome, and drugs as
possible risk modifiers. The hypothesis can be tested using animal models and by
a trial of carnitine supplementation in siblings of probands. Perhaps the lack of
any Recommended Dietary Allowance for carnitine in infants should be reviewed.
Also see the video abstract here: https://youtu.be/BuRH_jSjX5Y.
PMID- 28703321
TI - Overexpression miR-211-5p hinders the proliferation, migration, and invasion of
thyroid tumor cells by downregulating SOX11.
AB - PURPOSE: This study was aimed to investigate the relationship between miR-211-5p
and SOX11, and the effects of their interaction on the proliferation, viability,
and invasion of human thyroid cancer (TC) cells. METHODS: We used quantitative
real-time PCR (qRT-PCR) to determine the expression of miR-211-5p and SOX11mRNA
in the thyroid tumorous and the adjacent tissues. The target relationship between
miR-211-5p and SOX11 was confirmed using dual luciferase reporter gene assay.
Flow cytometry, colony formation assay, Transwell assay, and MTT assay were
performed to determine the cell-cycle progression, cell apoptosis, proliferation
and invasion, respectively. In addition, the tumor formation assay in nude mice
was done to assess the effect of miR-211-5p on TC development in vivo. RESULTS:
MiR-211-5p was underexpressed, whereas SOX11 was overexpressed in TC. The
overexpression of miR-211-5p inhibited the expression of SOX11. The cell cycle
was arrested and the proliferation as well as invasiveness was suppressed by
exogenous miR-211-5p in TC cell line. The antitumor role of miR-211-5p was proved
by the animal experiment. CONCLUSION: MiR-211-5p affected the viability,
proliferation and invasion of TC by negatively regulating SOX11 expression.
PMID- 28703322
TI - The Drosophila simulans Y chromosome interacts with the autosomes to influence
male fitness.
AB - The Y chromosome should degenerate because it cannot recombine. However, male
limited transmission increases selection efficiency for male-benefit alleles on
the Y, and therefore, Y chromosomes should contribute significantly to variation
in male fitness. This means that although the Drosophila Y chromosome is small
and gene-poor, Y-linked genes are vital for male fertility in Drosophila
melanogaster and the Y chromosome has large male fitness effects. It is unclear
whether the same pattern is seen in the closely related Drosophila simulans. We
backcrossed Y chromosomes from three geographic locations into five genetic
backgrounds and found strong Y and genetic background effects on male fertility.
There was a significant Y-background interaction, indicating substantial
epistasis between the Y and autosomal genes affecting male fertility. This
supports accumulating evidence that interactions between the Y chromosome and the
autosomes are key determinants of male fitness.
PMID- 28703323
TI - Professional oral health care for preventing nursing home-acquired pneumonia: A
cost-effectiveness and value of information analysis.
AB - AIM: Professional oral health care (POHC) prevents nursing home-acquired
pneumonia (NHAP) and its related mortality. We assessed the cost-effectiveness of
POHC versus no POHC (nPOHC) and the monetary value of eliminating uncertainty by
future research. METHODS: A German public-private payer perspective was adopted.
A Markov model was used, following long-term care residents from admission to
death. Cost-effectiveness was estimated as Euro/disability-adjusted life year
(DALY) using Monte Carlo microsimulations. Value-of-information analyses were
performed. The willingness-to-pay threshold/DALY was assumed to be 66% (range 50%
100%) of per-capita gross domestic product (GDP). RESULTS: nPOHC was less costly
(?3,024) but also less effective (0.89 DALYs) than POHC (?10,249, 0.55 DALYs).
For most presumed payers, POHC was cost-effective. The cost-effectiveness of POHC
was higher in smokers, underweight or pulmonary disease patients. Eliminating
uncertainty about the NHAP costs, NHAP incidence/mortality, and POHC
effectiveness would result in an expected net value of 47 million ?/year (and
even higher values at lower GDP thresholds), and is likely to decrease with time.
CONCLUSIONS: Within the chosen setting and on the basis of current evidence, POHC
was cost-effective. Given the detected uncertainty, further research seems
warranted.
PMID- 28703324
TI - Scaling range sizes to threats for robust predictions of risks to biodiversity.
AB - Assessments of risk to biodiversity often rely on spatial distributions of
species and ecosystems. Range-size metrics used extensively in these assessments,
such as area of occupancy (AOO), are sensitive to measurement scale, prompting
proposals to measure them at finer scales or at different scales based on the
shape of the distribution or ecological characteristics of the biota. Despite its
dominant role in red-list assessments for decades, appropriate spatial scales of
AOO for predicting risks of species' extinction or ecosystem collapse remain
untested and contentious. There are no quantitative evaluations of the scale
sensitivity of AOO as a predictor of risks, the relationship between optimal AOO
scale and threat scale, or the effect of grid uncertainty. We used stochastic
simulation models to explore risks to ecosystems and species with clustered,
dispersed, and linear distribution patterns subject to regimes of threat events
with different frequency and spatial extent. Area of occupancy was an accurate
predictor of risk (0.81<|r|<0.98) and performed optimally when measured with grid
cells 0.1-1.0 times the largest plausible area threatened by an event. Contrary
to previous assertions, estimates of AOO at these relatively coarse scales were
better predictors of risk than finer-scale estimates of AOO (e.g., when
measurement cells are <1% of the area of the largest threat). The optimal scale
depended on the spatial scales of threats more than the shape or size of biotic
distributions. Although we found appreciable potential for grid-measurement
errors, current IUCN guidelines for estimating AOO neutralize geometric
uncertainty and incorporate effective scaling procedures for assessing risks
posed by landscape-scale threats to species and ecosystems.
PMID- 28703325
TI - Effectiveness of protected areas for vertebrates based on taxonomic and
phylogenetic diversity.
AB - Establishing protected areas is the primary goal and tool for preventing
irreversible biodiversity loss. However, the effectiveness of protected areas
that target specific species has been questioned for some time because targeting
key species for conservation may impair the integral regional pool of species
diversity and phylogenetic and functional diversity are seldom considered. We
assessed the efficacy of protected areas in China for the conservation of
phylogenetic diversity based on the ranges and phylogenies of 2279 terrestrial
vertebrates. Phylogenetic and taxonomic diversity were strongly and positively
correlated, and only 12.1-43.8% of priority conservation areas are currently
protected. However, the patterns and coverage of phylogenetic diversity were
affected when weighted by species richness. These results indicated that in
China, protected areas targeting high species richness protected phylogenetic
diversity well overall but failed to do so in some regions with more unique or
threatened communities (e.g., coastal areas of eastern China, where severely
threatened avian communities were less protected). Our results suggest that the
current distribution of protected areas could be improved, although most
protected areas protect both taxonomic and phylogenetic diversity.
PMID- 28703326
TI - Letter from the new Editor-in-Chief.
PMID- 28703327
TI - Testing the Situationism Scale in Europe: Scale validation, self-regulation and
regional differences.
AB - The term situationism refers to an individual's belief about the importance of a
behaviour's context. This study tested whether the degree of situationism
expressed by individuals in various regions of Europe was consistent with self
regulation and cross-cultural theories. The English version of a Situationism
Scale (measuring beliefs about the relation between the environment and one's own
behaviour) was translated into five additional languages: Dutch, German,
Hungarian, Italian and Slovenian. Young adults (N = 1106, MAge = 22.9 years, 79%
female) across Europe responded to one of the six language versions of the scale
as part of a larger survey. Results indicated that: new language versions were
psychometrically valid; there was a positive relation between situationism and
the use of situation-control strategies; and situationism was higher for
individuals from regions that are Eastern European and relatively more
interdependent, compared with individuals from regions that are Western European
and relatively less interdependent. As the first evaluation of the Situationism
Scale outside America, this study supports the Scale's validity and suggests not
only may some effects of situationism be universal, but between- and within
culture differences in situationism exist. Overall, when making judgments and
decisions about the self, cultural background and individual differences in
situationism may come into play.
PMID- 28703329
TI - Relationship between collectivism and corruption in American and Chinese books: A
historical perspective.
AB - Previous research on the relationship between collectivism and corruption has not
investigated their co-variation over time. In this study, we use Google Ngram
Viewer to track the frequency of words related to collectivism and corruption in
American books (1800-2000) and in Chinese Books (1970-2008). The results
demonstrate that a positive association between the usage of these terms during
the periods in both Chinese and American books, with changes in words related to
collectivism preceding changes in words related to corruption in American books.
The theoretical and practical implications are also discussed.
PMID- 28703328
TI - Insight into infection-mediated prostate damage: Contrasting patterns of C
reactive protein and prostate-specific antigen levels during infection.
AB - BACKGROUND: To investigate mechanisms underlying our previous observation of a
large rise in serum prostate-specific antigen, a marker of prostate pathology,
during both sexually transmitted and systemic infections, we measured serum high
sensitivity C-reactive protein (hsCRP), a marker of systemic inflammation, in our
previous case-control study of young, male US military members and compared our
findings to those for PSA. METHODS: We measured hsCRP before and during infection
for 299 chlamydia, 112 gonorrhea, and 59 non-chlamydial, non-gonococcal
urethritis (NCNGU) cases; before and after infection for 55 infectious
mononucleosis (IM) and 90 other systemic/non-genitourinary cases; and for 220-256
controls. RESULTS: Only gonorrhea cases were significantly more likely to have a
large hsCRP rise (>=1.40 mg/L or >=239%) during infection than controls (P <
0.01). However, gonorrhea, IM, and other systemic/non-genitourinary cases were
more likely to have a rise of any magnitude up to one year post-diagnosis than
controls (p = 0.038-0.077). CONCLUSIONS: These findings, which differ from those
for PSA, suggest distinct mechanisms of elevation for hsCRP and PSA, and support
both direct (eg, prostate infection) and indirect (eg, systemic inflammation
mediated prostate cell damage) mechanisms for PSA elevation. Future studies
should explore our PSA findings further for their relevance to both prostate
cancer screening and risk.
PMID- 28703330
TI - Struggling to be liked: The prospective effect of trait self-control on social
desirability and the moderating role of agreeableness.
AB - Drawing from the literature on the interpersonal functions of self-control, we
examined longitudinal associations between trait self-control and social
desirability, using a survey of the general population in the Netherlands. Trait
self-control at baseline was positively associated with social desirability at a
follow-up, even when controlling for prior levels of social desirability. That
is, high self-control contributed to individuals' tendency to give socially
desirable responses in self-reports. This effect was moderated by individual
differences in agreeableness. Highly agreeable individuals were more likely to
"use" their self-regulatory resources to respond in a socially desirable manner,
compared to less agreeable individuals, suggesting that individuals might use
self-regulatory resources in a way consistent with the motivational bases of
their personality.
PMID- 28703331
TI - High-resolution diffusion tensor imaging in cervical spondylotic myelopathy: a
preliminary follow-up study.
AB - Diffusion imaging is a promising technique as it can provide microstructural
tissue information and thus potentially show viable changes in spinal cord.
However, the traditional single-shot imaging method is limited as a result of
various image artifacts. In order to improve measurement accuracy, we used a
newly developed, multi-shot, high-resolution, diffusion tensor imaging (DTI)
method to investigate diffusion metric changes and compare them with T2 -weighted
(T2W) images before and after decompressive surgery for cervical spondylotic
myelopathy (CSM). T2W imaging, single-shot DTI and multi-shot DTI were employed
to scan seven patients with CSM before and 3 months after decompressive surgery.
High signal intensities were scored using the T2 W images. DTI metrics, including
fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD) and
mean diffusivity (MD), were quantified and compared pre- and post-surgery. In
addition, the relationship between imaging metrics and neurological assessments
was examined. The reproducibility of multi-shot DTI was also assessed in 10
healthy volunteers. Post-surgery, the mean grade of cervical canal stenosis was
reduced from grade 3 to normal after 3 months. Compared with single-shot DTI,
multi-shot DTI provided better images with lower artifact levels, especially
following surgery, as a result of reduced artifacts from metal implants. The new
method also showed acceptable reproducibility. Both FA and RD values from the new
acquisition showed significant differences post-surgery (FA, p = 0.026; RD, p =
0.048). These changes were consistent with neurological assessments. In contrast,
T2W images did not show significant changes before and after surgery. Multi-shot
diffusion imaging showed improved image quality over single-shot DWI, and
presented superior performance in diagnosis and recovery monitoring for patients
with CSM compared with T2W imaging. DTI metrics can reflect the pathological
conditions of spondylotic spinal cord quantitatively and may serve as a sensitive
biomarker for potential CSM management.
PMID- 28703332
TI - Validation of biplane high-speed fluoroscopy combined with two different
noninvasive tracking methodologies for measuring in vivo distal limb kinematics
of the horse.
AB - REASON FOR PERFORMING STUDY: Biplane high-speed fluoroscopy is a new method for
gait analysis of the equine distal extremity. This is the first study validating
the noninvasive tracking possibilities (Autoscoping and Scientific Rotoscoping)
taking equine anatomy into account. OBJECTIVES: To determine the resolution with
which Autoscoping and Scientific Rotoscoping depict motion of the equine
phalanges in comparison to the invasive gold standard marker-based registration.
STUDY DESIGN: Comparative ex vivo study. METHODS: In 5 distal extremities of
slaughtered ponies, 3 or 4 tantalum beads with 1 mm diameter were implanted in
each of the proximal, middle and distal phalangeal bones. Three-dimensional
models of the bones were reconstructed using computed tomographic data (120 kV,
50 mA, slice thickness 1 mm, increment 0.5). The beads were digitally removed
from the bone models. Biplane fluoroscopic videos were taken at 69.5 +/- 3.5 kV,
102.5 +/- 22.5 mA, 500 frames/s and 0.5 ms shutter speed. The 5 specimens were
moved in the trial field of the biplane fluoroscopic setup in a step-like motion
(simulation of landing, main stance phase, lift-off). Marker-based registration,
Autoscoping and Scientific Rotoscoping were carried out. For statistical analysis
agreement was computed as percentiles, mean and s.d. RESULTS: The medians of
Scientific Rotoscoping ranged from 0.16 to 0.66 mm in translations and 0.43 to
2.78 degrees in rotations, while values for Autoscoping were 0.13-0.70 mm and
0.28-2.39 degrees respectively. With 2 exceptions, all differences between
methods were statistically significant. Scientific Rotoscoping is more time
efficient than Autoscoping and results in smaller maximum errors. MAIN
LIMITATIONS: The experimental set-up was specifically designed to accommodate in
vivo requirements. Autoscoping was not manually corrected but rather expected to
work automatically. CONCLUSIONS: It is possible to noninvasively apply both
Autoscoping and Scientific Rotoscoping for gait analysis of the equine phalanges
with high precision. The summary is available in Chinese - see supporting
information.
PMID- 28703333
TI - Bone tissue response following local drug delivery of bisphosphonate through
titanium oxide nanotube implants in a rabbit model.
AB - OBJECTIVES: The objective of this study was to evaluate whether surface chemistry
controlled TiO2 nanotube structures may serve as a local drug delivery system for
zoledronic acid improving implant-bone support. METHODS: Twenty-four screw-shaped
Ti implants with surface chemistry-controlled TiO2 nanotube structures were
prepared and divided into a zoledronic acid-formatted test and a native control
group. The implants were inserted into contra-lateral femoral condyles in 12 New
Zealand White rabbits. Bone support was evaluated using resonance frequency
analysis (RFA) and removal torque (RTQ), as well as histometric analysis
following a 3-weeks healing interval. RESULTS: Zoledronic acid-formatted TiO2
nanotube test implants showed significantly improved implant stability and
osseointegration measured using RFA and RTQ compared with control (p < 0.05), and
showed significantly enhanced new bone formation within the root of the threads
compared with control (p < 0.05). CONCLUSIONS: TiO2 nanotube implants may prove
to be a significant delivery system for drugs or biologic agents aimed at
supporting local bone formation. Additional study of candidate drugs/agents,
optimized dosage and release kinetics is needed prior to evaluation in clinical
settings.
PMID- 28703334
TI - A case of kaposiform haemangioendothelioma successfully and safely treated with
sirolimus.
PMID- 28703335
TI - GATA3 as a putative marker of breast cancer metastasis-A retrospective
immunohistochemical study.
AB - Diagnostic verification of breast cancer metastasis with histopathology and
imaging analysis is essential to determine tumor staging. The aim of this study
was to validate the utility of GATA3 immunohistochemistry as a diagnostic marker
for breast cancer metastases and metastases of unknown primary origin.
Retrospective immunohistochemical analysis of GATA3 expression in 164 breast
cancer metastases diagnosed between 2004 and 2014 showed a striking difference
between mammaglobin and GATA3 expression (51.2% vs 94% positivity). These
findings highlight GATA3 as a more reliable and sensitive diagnostic marker for
breast cancer metastases and possibly metastatic tumors of unknown origin than
mammaglobin.
PMID- 28703336
TI - A genome-wide association study reveals candidate genes for the supernumerary
nipple phenotype in sheep (Ovis aries).
AB - Genome-wide association studies (GWASs) have been widely applied in livestock to
identify genes associated with traits of economic interest. Here, we conducted
the first GWAS of the supernumerary nipple phenotype in Wadi sheep, a native
Chinese sheep breed, based on Ovine Infinium HD SNP BeadChip genotypes in a total
of 144 ewes (75 cases with four teats, including two normal and two supernumerary
teats, and 69 control cases with two teats). We detected 63 significant SNPs at
the chromosome-wise threshold. Additionally, one candidate region (chr1: 170.723
170.734 Mb) was identified by haplotype-based association tests, with one SNP
(rs413490006) surrounding functional genes BBX and CD47 on chromosome 1 being
commonly identified as significant by the two mentioned analyses. Moreover, Gene
Ontology enrichment for the significant SNPs identified by the GWAS analysis was
functionally clustered into the categories of receptor activity and synaptic
membrane. In addition, pathway mapping revealed four promising pathways (Wnt,
oxytocin, MAPK and axon guidance) involved in the development of the
supernumerary nipple phenotype. Our results provide novel and important insights
into the genetic mechanisms underlying the phenotype of supernumerary nipples in
mammals, including humans. These findings may be useful for future breeding and
genetics in sheep and other livestock.
PMID- 28703337
TI - Paternal age as an independent factor does not affect embryo quality and
pregnancy outcomes of testicular sperm extraction-intracytoplasmic sperm
injection in azoospermia.
AB - This study was performed to evaluate the independent influence of paternal age
affecting embryo development and pregnancy using testicular sperm extraction
(TESE)-intracytoplasmic sperm injection (ICSI) in obstructive azoospermia (OA)
and nonobstructive azoospermia (NOA). Paternal patients were divided into the
following groups: <=30 years, 31-35 years, 36-40 years, 41-45 years and >=46
years. There were no differences in the rates of fertilisation or embryo quality
according to paternal and maternal age. However, clinical pregnancy and
implantation rates were significantly lower between those >=46 years of paternal
age compared with other age groups. Fertilisation rate was higher in the OA than
the NOA, while embryo quality, pregnancy and delivery results were similar.
Clinical pregnancy and implantation rates were significantly lower for patients
>=46 years of paternal age compared with younger age groups. In conclusion,
fertilisation using TESE in azoospermia was not affected by the independent
influence of paternal age; however, as maternal age increased concomitantly with
paternal age, rates of pregnancy and delivery differed between those with
paternal age <41 years and >=46 years. Therefore, paternal age >=46 years old
should be considered when applying TESE-ICSI in cases of azoospermia, and
patients should be advised of the associated low pregnancy rates.
PMID- 28703338
TI - Response to 'There is a place in current obstetric practice for planned vaginal
breech birth'.
PMID- 28703339
TI - The Synthesis and Photophysical Analysis of a Series of 4
Nitrobenzochalcogenadiazoles for Super-Resolution Microscopy.
AB - A series of 4-nitrobenzodiazoles with atomic substitution through the chalcogen
group were synthesised and their photophysical properties analysed with a view
for use in single-molecule localisation microscopy. Sub-diffraction resolution
imaging was achieved for silica nanoparticles coated with each dye. Those
containing larger atoms were favoured for super-resolution microscopy due to a
reduced blink rate (required for stochastic events to be localised). The sulfur
containing molecule was deemed most amenable for widespread use due to the ease
of synthetic manipulation compared to the selenium-containing derivative.
PMID- 28703340
TI - Core-Satellite Polydopamine-Gadolinium-Metallofullerene Nanotheranostics for
Multimodal Imaging Guided Combination Cancer Therapy.
AB - Integration of magnetic resonance imaging (MRI) and other imaging modalities is
promising to furnish complementary information for accurate cancer diagnosis and
imaging-guided therapy. However, most gadolinium (Gd)-chelator MR contrast agents
are limited by their relatively low relaxivity and high risk of released-Gd-ions
associated toxicity. Herein, a radionuclide-64 Cu-labeled doxorubicin-loaded
polydopamine (PDA)-gadolinium-metallofullerene core-satellite nanotheranostic
agent (denoted as CDPGM) is developed for MR/photoacoustic (PA)/positron emission
tomography (PET) multimodal imaging-guided combination cancer therapy. In this
system, the near-infrared (NIR)-absorbing PDA acts as a platform for the assembly
of different moieties; Gd3 N@C80 , a kind of gadolinium metallofullerene with
three Gd ions in one carbon cage, acts as a satellite anchoring on the surface of
PDA. The as-prepared CDPGM NPs show good biocompatibility, strong NIR absorption,
high relaxivity (r 1 = 14.06 mM-1 s-1 ), low risk of release of Gd ions, and NIR
triggered drug release. In vivo MR/PA/PET multimodal imaging confirms effective
tumor accumulation of the CDPGM NPs. Moreover, upon NIR laser irradiation, the
tumor is completely eliminated with combined chemo-photothermal therapy. These
results suggest that the CDPGM NPs hold great promise for cancer theranostics.
PMID- 28703341
TI - Esophageal function testing: Billing and coding update.
AB - BACKGROUND AND PURPOSE: Esophageal function testing is being increasingly
utilized in diagnosis and management of esophageal disorders. There have been
several recent technological advances in the field to allow practitioners the
ability to more accurately assess and treat such conditions, but there has been a
relative lack of education in the literature regarding the associated Common
Procedural Terminology (CPT) codes and methods of reimbursement. This review,
commissioned and supported by the American Neurogastroenterology and Motility
Society Council, aims to summarize each of the CPT codes for esophageal function
testing and show the trends of associated reimbursement, as well as recommend
coding methods in a practical context. We also aim to encourage many of these
codes to be reviewed on a gastrointestinal (GI) societal level, by providing
evidence of both discrepancies in coding definitions and inadequate reimbursement
in this new era of esophageal function testing.
PMID- 28703342
TI - Evaluation of direct antifungal susceptibility testing methods of Candida spp.
from positive blood culture bottles.
AB - BACKGROUND: Blood culture is the gold standard diagnostic method in candidemia in
spite of long result time and low sensitivity rate. Early diagnosis is crucial
for management of candidemia because a delay in treatment is related with
increased mortality. We aimed to evaluate the direct applicability of antifungal
susceptibility testing methods from positive blood culture bottles to save at
least 24 hours. METHODS: Blood culture bottles were inoculated with 62 Candida
isolates. Etest and broth microdilution (BMD) methods for six antifungals, disk
diffusion (DD) method for two antifungals were performed, both directly from
bottles and standardly. RESULTS: Essential agreements between direct and standard
Etest methods were 87.1% for caspofungin and >90% for other antifungals, but the
agreements of them with reference BMD were relatively low. Essential agreement
between direct and standard BMD was >93%. Correlation between direct and standard
DD methods was very high, negative correlations were observed between reference
BMD and DD methods. CONCLUSION: BMD is a reference method to evaluate the
antifungal susceptibility, direct application of BMD might provide reliable
results at least 24 hours earlier. Direct DD method may be a qualitative
alternative. Direct susceptibility testing methods may be very useful to
initiating the appropriate treatment on time.
PMID- 28703343
TI - Contact anaphylaxis caused by Basic Blue 99 in hair dye.
PMID- 28703344
TI - Allergic contact dermatitis caused by copper in a malachite necklace.
PMID- 28703345
TI - Is octocrylene a frequent contact allergen?
PMID- 28703346
TI - Two cases of eczematous drug eruption caused by oral tacrolimus administration.
PMID- 28703347
TI - Non-pigmenting fixed drug eruption with mixed features of acute generalized
exanthematous pustulosis induced by pseudoephedrine: a case report.
PMID- 28703348
TI - Allergic contact dermatitis caused by wet wipes containing steareth-10: Is
stearyl alcohol to blame?
PMID- 28703349
TI - Airborne contact dermatitis caused by fragrance diffusers in Uber cars.
PMID- 28703350
TI - Photoallergic contact dermatitis caused by quinidine sulfate in a caregiver.
PMID- 28703351
TI - A comparative study between responses of isolated bovine and equine digital
arteries to vasoactive mediators.
AB - Hemodynamic perturbations, partly resulting from abnormal vasoconstriction of
digital vessels, have been implicated in the pathogenesis of bovine and equine
laminitis. This study compared the responsiveness of isolated bovine (BDA) and
equine (EDA) digital arteries to pharmacological agents that stimulate receptor
systems involved in the regulation of normal vessel tone. The role of the
endothelium and the short- and longer-term effects of an experimentally induced
endothelial damage were also evaluated. Species-related differences were found in
the vessel reactivity to all of the receptor agonists tested. In intact BDA, as
compared to intact EDA, norepinephrine was a more effective vasoconstrictor, 5
hydroxytryptamine a more effective but less potent vasoconstrictor, isoproterenol
a less effective vasodilator and carbamylcholine a less potent vasodilator. In
BDA, but not in EDA, the contractile responses to norepinephrine and 5
hydroxytryptamine were enhanced immediately after endothelium removal. However,
the contractile reactivity of denuded BDA returned to basal values following
overnight incubation. The differences suggest species specificity for the
pathophysiology of digital vasomotor tone and function in horses and cattle.
PMID- 28703352
TI - AtPDS overexpression in tomato: exposing unique patterns of carotenoid self
regulation and an alternative strategy for the enhancement of fruit carotenoid
content.
AB - The regulation of plant carotenogenesis is an active research area for both
biological discovery and practical implementation. In tomato (Solanum
lycopersicum), we demonstrate additional bottlenecks exist in the poly-cis
transformation of phytoene to lycopene in the context of ripening-induced PSY1
expression and activity and reveal phytoene desaturase (PDS), as a target for
manipulation towards elevated lycopene content in maturing tomato fruit.
Overexpression of Arabidopsis PDS, AtPDS, elevated PDS transcript abundance in
all aerial tissues resulting in both altered carotenoid accumulation and
associated pathway gene expression in a tissue-specific manner. Significant
increases in downstream carotenoids (all-trans-lycopene and beta-carotene) and
minimal changes in carotenogenic gene expression (carotenoid isomerase-like 1,
CRTIL1) suggest overexpression of heterologous AtPDS in tomato circumvents
endogenous regulatory mechanism observed with previous strategies. In transgenic
leaves, depletion of the PDS substrate, phytoene, was accompanied by minor, but
significant increases in xanthophyll production. Alterations in the leaf
carotenogenic transcript profile, including the upstream MEP pathway, were
observed revealing unique feedback and feedforward regulatory mechanisms in
response to AtPDS overexpression. AtPDS overexpression in the background of the
tangerine (carotenoid isomerase, CRTISO) mutant exposes its potential in
elevating downstream cis-lycopene accumulation in ripe tomato fruit, as cis
lycopene is more bioavailable yet less abundant than all-trans-lycopene in the
wild-type control. In summary, we demonstrate the limitation of PDS in ripening
fruit, its utility in modifying carotenoid profiles towards improved quality, and
reveal novel carotenoid pathway feedback regulation.
PMID- 28703353
TI - Inhibition of glial hemichannels by boldine treatment reduces neuronal suffering
in a murine model of Alzheimer's disease.
AB - The contribution of reactive gliosis to the pathological phenotype of Alzheimer's
disease (AD) opened the way for therapeutic strategies targeting glial cells
instead of neurons. In such context, connexin hemichannels were proposed recently
as potential targets since neuronal suffering is alleviated when connexin
expression is genetically suppressed in astrocytes of a murine model of AD. Here,
we show that boldine, an alkaloid from the boldo tree, inhibited hemichannel
activity in astrocytes and microglia without affecting gap junctional
communication in culture and acute hippocampal slices. Long-term oral
administration of boldine in AD mice prevented the increase in glial hemichannel
activity, astrocytic Ca2+ signal, ATP and glutamate release and alleviated
hippocampal neuronal suffering. These findings highlight the important
pathological role of hemichannels in AD mice. The neuroprotective effect of
boldine treatment might provide the basis for future pharmacological strategies
that target glial hemichannels to reduce neuronal damage in neurodegenerative
diseases.
PMID- 28703354
TI - Identification of sequence polymorphisms in the mitochondrial cytochrome c
oxidase genes as risk factors for hepatocellular carcinoma.
AB - BACKGROUND: Single nucleotide polymorphisms (SNPs) accumulated in the
mitochondrial DNA (mtDNA) is susceptible to the tumor formation. We discovered
previously that SNPs in the mitochondrial displacement loop (D-loop) was
associated with the risk of hepatocellular carcinoma (HCC). METHODS: The
cytochrome c oxidase (COX) genes of mtDNA were sequenced between 107 HCC patients
and 100 matched healthy controls. The chi2 test was used to analyze single SNPs'
statistical difference between HCC patients and healthy controls. RESULTS: In
this study, cancer risk-associated SNPs in the COX genes of mtDNA coding region
were assessed in HCC patients and health controls. The nucleotide position at
site 9545A/G (P=.036) was identified its association for HCC with the 9545G
allele susceptible to cancer risk. CONCLUSIONS: The SNPs in the COX genes may
help us to evaluate the cancer risk of HCC.
PMID- 28703355
TI - Neuronal representation of individual heroin choices in the orbitofrontal cortex.
AB - Drug addiction is a harmful preference for drug use over and at the expense of
other non-drug-related activities. We previously identified in the rat
orbitofrontal cortex (OFC) a mechanism that influences individual preferences
between cocaine use and an alternative action rewarded by a non-drug reward (i.e.
sweet water). Here, we sought to test the generality of this mechanism to a
different addictive drug, heroin. OFC neuronal activity was recorded while rats
responded for heroin or the alternative non-drug reward separately or while they
chose between the two. First, we found that heroin-rewarded and sweet water
rewarded actions were encoded by two non-overlapping OFC neuronal populations and
that the relative size of the heroin population represented individual drug
choices. Second, OFC neurons encoding the preferred action-which was the non-drug
action in the large majority of individuals-progressively fired more than non
preferred action-coding neurons 1 second after the onset of choice trials and
around 1 second before the preferred action was actually chosen, suggesting a pre
choice neuronal competition for action selection. Together with a previous study
on cocaine choice, the present study on heroin choice reveals important
commonalities in how OFC neurons encode individual drug choices and preferences
across different classes of drugs. It also reveals some drug-specific differences
in OFC encoding activity. Notably, the proportion of neurons that non-selectively
encode both the drug and the non-drug reward was higher when the drug was heroin
(present study) than when it was cocaine (previous study). We will discuss the
potential functional significance of these commonalities and differences in OFC
neuronal activity across different drugs for understanding drug choice.
PMID- 28703356
TI - A Second-Coordination-Sphere Strategy to Modulate Nickel- and Palladium-Catalyzed
Olefin Polymerization and Copolymerization.
AB - Transition-metal-catalyzed copolymerization reactions of olefins with polar
functionalized comonomers are highly important and also highly challenging. A
second-coordination-sphere strategy was developed to address some of the
difficulties encountered in these copolymerization reactions. A series of alpha
diimine ligands bearing nitrogen-containing second coordination spheres were
prepared and characterized. The properties of the corresponding nickel and
palladium catalysts in ethylene polymerizations and copolymerizations were
investigated. In the nickel system, significant reduction in polymer branching
density was observed, while lower polymer branching densities, as well as a wider
range of polar monomer substrates, were achieved in the palladium system. Control
experiments and computational results reveal the critical role of the metal
nitrogen interaction in these polymerization and copolymerization reactions.
PMID- 28703357
TI - Evolutionary allometry reveals a shift in selection pressure on male horn size.
AB - How selection pressures acting within species interact with developmental
constraints to shape macro-evolutionary patterns of species divergence is still
poorly understood. In particular, whether or not sexual selection affects
evolutionary allometry, the increase in trait size with body size across species,
of secondary sexual characters, remains largely unknown. In this context, bovid
horn size is an especially relevant trait to study because horns are present in
both sexes, but the intensity of sexual selection acting on them is expected to
vary both among species and between sexes. Using a unique data set of sex
specific horn size and body mass including 91 species of bovids, we compared the
evolutionary allometry between horn size and body mass between sexes while
accounting for both the intensity of sexual selection and phylogenetic
relationship among species. We found a nonlinear evolutionary allometry where the
allometric slope decreased with increasing species body mass. This pattern, much
more pronounced in males than in females, suggests either that horn size is
limited by some constraints in the largest bovids or is no longer the direct
target of sexual selection in very large species.
PMID- 28703358
TI - Catalytic Asymmetric Total Synthesis and Stereochemical Revision of Leucinostatin
A: A Modulator of Tumor-Stroma Interaction.
AB - Total synthesis of leucinostatin A, a modulator of tumor-stroma interactions,
using asymmetric catalyses, a nitroaldol reaction, thioamide-aldol reaction,
Strecker-type reaction, and alcoholysis of 3-methylglutaric anhydride, is
described. We demonstrated the applicability of the established catalytic
asymmetric processes to the synthesis of molecules with a complex structure.
Careful analysis of the NMR data, HPLC profiles, and biological activity revealed
that the correct structure of leucinostatin A is the epimeric form of the
reported structure; the secondary alcohol within the AHMOD residue has an R
configuration.
PMID- 28703359
TI - A modified surgical approach for giant left coronary arterial aneurysm.
PMID- 28703360
TI - Model averaging for robust assessment of QT prolongation by concentration
response analysis.
AB - Assessing the QT prolongation potential of a drug is typically done based on
pivotal safety studies called thorough QT studies. Model-based estimation of the
drug-induced QT prolongation at the estimated mean maximum drug concentration
could increase efficiency over the currently used intersection-union test.
However, robustness against model misspecification needs to be guaranteed in
pivotal settings. The objective of this work was to develop an efficient, fully
prespecified model-based inference method for thorough QT studies, which controls
the type I error and provides satisfactory test power. This is achieved by model
averaging: The proposed estimator of the concentration-response relationship is a
weighted average of a parametric (linear) and a nonparametric (monotonic I
splines) estimator, with weights based on mean integrated square error. The
desired properties of the method were confirmed in an extensive simulation study,
which demonstrated that the proposed method controlled the type I error
adequately, and that its power was higher than the power of the nonparametric
method alone. The method can be extended from thorough QT studies to the analysis
of QT data from pooled phase I studies.
PMID- 28703361
TI - Non-decoupled morphological evolution of the fore- and hindlimb of sabretooth
predators.
AB - Specialized organisms are useful for exploring the combined effects of selection
of functional traits and developmental constraints on patterns of phenotypic
integration. Sabretooth predators are one of the most interesting examples of
specialization among mammals. Their hypertrophied, sabre-shaped upper canines and
their powerfully built forelimbs have been interpreted as adaptations to a highly
specialized predatory behaviour. Given that the elongated and laterally
compressed canines of sabretooths were more vulnerable to fracture than the
shorter canines of conical-tooth cats, it has been long hypothesized that the
heavily muscled forelimbs of sabretooths were used for immobilizing prey before
developing a quick and precise killing bite. However, the effect of this unique
adaptation on the covariation between the fore- and the hindlimb has not been
explored in a quantitative fashion. In this paper, we investigate if the
specialization of sabretooth predators decoupled the morphological variation of
their forelimb with respect to their hindlimb or, in contrast, both limbs vary in
the same fashion as in conical-tooth cats, which do not show such extreme
adaptations in their forelimb. We use 3D geometric morphometrics and different
morphological indices to compare the fore- and hindlimb of conical- and
sabretooth predators. Our results indicate that the limb bones of sabretooth
predators covary following the same trend of conical-tooth cats. Therefore, we
show that the predatory specialization of sabretooth predators did not result in
a decoupling of the morphological evolution of their fore- and hindlimbs. The
role of developmental constraints and natural selection on this coordinate
variation between the fore- and the hindlimb is discussed in the light of this
new evidence.
PMID- 28703362
TI - In Vivo Delivery and Activation of Masked Fluorogenic Hydrolase Substrates by
Endogenous Hydrolases in C. elegans.
AB - Protein expression and localization are often studied in vivo by tagging
molecules with green fluorescent protein (GFP), yet subtle changes in protein
levels are not easily detected. To develop a sensitive in vivo method to amplify
fluorescence signals and allow cell-specific quantification of protein abundance
changes, we sought to apply an enzyme-activated cellular fluorescence system in
vivo by delivering ester-masked fluorophores to Caenorhabditis elegans neurons
expressing porcine liver esterase (PLE). To aid uptake into sensory neuron
membranes, we synthesized two novel fluorogenic hydrolase substrates with long
hydrocarbon tails. Recombinant PLE activated these fluorophores in vitro. In vivo
activation occurred in sensory neurons, along with potent activation in
intestinal lysosomes quantifiable by imaging and microplate and partially
attributable to gut esterase 1 (GES-1) activity. These data demonstrate the
promise of biorthogonal hydrolases and their fluorogenic substrates as in vivo
neuronal imaging tools and for characterizing endogenous C. elegans hydrolase
substrate specificities.
PMID- 28703363
TI - Reflectance confocal microscopy for the diagnosis of Galli-Galli disease.
PMID- 28703364
TI - Computed tomographic characteristics of the thyroid glands in eight hyperthyroid
cats pre- and postmethimazole treatment compared with seven euthyroid cats.
PMID- 28703365
TI - Phototherapy in systemic sclerosis: Review.
AB - Systemic scleroderma-also known as systemic sclerosis (SSc)-is a chronic systemic
connective tissue disease characterized by collagen deposition in cutaneous and
internal organs, leading to skin sclerosis and multiple organ fibrosis. The
pathogenesis is complex and remains poorly understood. Treatment is based on
organ involvement and requires a multidisciplinary approach. Skin sclerosis can
cause disability, leading to decreasing quality of life. Various systemic
antifibrotic therapies have been used; however, most have unsatisfactory results.
Recently, phototherapy and in particular ultraviolet A (UVA) has been used to
treat skin sclerosis in SSc patients with satisfactory results. The main
mechanisms include lymphocyte apoptosis, cytokine alteration, inhibition of
collagen synthesis and increased collagenase production, and neovascularization,
leading to the breakdown of collagen fibrils resulting in skin softening or even
healing digital ulcers. Most studies reported that psoralen plus UVA (PUVA) and
UVA1 phototherapy improved clinical outcomes vis-a-vis skin sclerosis, joint
mobility, ulcers, and histopathology. PUVA and UVA1 phototherapy therefore have
potential as an alternative or adjunctive therapy for patients with SSc.
PMID- 28703366
TI - Synergistic Effect of TPD7 and Berberine against Leukemia Jurkat Cell Growth
through Regulating Ephrin-B2 Signaling.
AB - TPD7, a novel biphenyl urea taspine derivative, and berberine have presented
inhibition on VEGFR2 that can be regulated by ephrin-B2 reverse signaling through
interactions with the PDZ domain. The purpose of this study is to investigate the
inhibitory effect of the combination of TPD7 and berberine (TAB) on T-cell acute
lymphoblastic leukemia cell growth. TPD7 and berberine together synergistically
inhibited the proliferation of Jurkat cells. Also, the combination of TAB induced
G1 -phase cell-cycle arrest by downregulating the level of cyclin D1, cyclin E,
and CDC2. Furthermore, the combination of TAB significantly enhanced apoptosis in
Jurkat cells, and the apoptosis most likely resulted from the modulation of the
level of Bcl-2 family members. Most importantly, the concomitant treatment
simultaneously regulated the ephrin-B2 and VEGFR2 signaling, as well as modulated
the MEK/ERK and PTEN/PI3K/AKT/mTOR signaling. Therefore, the combination
treatment of TAB may be a promising therapeutic method in treating T-cell acute
lymphoblastic leukemia. Copyright (c) 2017 John Wiley & Sons, Ltd.
PMID- 28703367
TI - Temporal relationship between instantaneous pressure gradients and peak-to-peak
systolic ejection gradient in congenital aortic stenosis.
AB - OBJECTIVE: We sought to identify a time during cardiac ejection when the
instantaneous pressure gradient (IPG) correlated best, and near unity, with peak
to-peak systolic ejection gradient (PPSG) in patients with congenital aortic
stenosis. Noninvasive echocardiographic measurement of IPG has limited
correlation with cardiac catheterization measured PPSG across the spectrum of
disease severity of congenital aortic stenosis. A major contributor is the
observation that these measures are inherently different with a variable
relationship dependent on the degree of stenosis. DESIGN: Hemodynamic data from
cardiac catheterizations utilizing simultaneous pressure measurements from the
left ventricle (LV) and ascending aorta (AAo) in patients with congenital valvar
aortic stenosis was retrospectively reviewed over the past 5 years. The cardiac
cycle was standardized for all patients using the percentage of total LV ejection
time (ET). Instantaneous gradient at 5% intervals of ET were compared to PPSG
using linear regression and Bland-Altman analysis. RESULTS: A total of 22
patients underwent catheterization at a median age of 13.7 years (interquartile
range [IQR] 10.3-18.0) and median weight of 51.1 kg (IQR 34.2-71.6). The PPSG was
46.5 +/- 12.6 mm Hg (mean +/- SD) and correlated suboptimally with the maximum
and mean IPG. The midsystolic IPG (occurring at 50% of ET) had the strongest
correlation with the PPSG ( PPSG = 0.97(IPG50%)-1.12, R2 = 0.88), while the IPG
at 55% of ET was closest to unity ( PPSG = 0.997(IPG55%)-1.17, R2 = 0.87).
CONCLUSIONS: The commonly measured maximum and mean IPG are suboptimal estimates
of the PPSG in congenital aortic stenosis. Using catheter-based data, IPG at 50%
55% of ejection correlates well with PPSG. This may allow for a more accurate
estimation of PPSG via noninvasive assessment of IPG.
PMID- 28703369
TI - Thomas E. Starzl, MD, PhD: Father of Transplantation-March 11, 1926-March 4,
2017.
PMID- 28703370
TI - Urgent Driveline Repair Under Catecholamine Support After Total Driveline Cut.
PMID- 28703371
TI - Normothermic Machine Perfusion Using an Air/Oxygen Mixer for Reconditioning a
Liver From a Marginal Brain Death Donor.
PMID- 28703372
TI - Extracorporeal Lung Support in Acute Chest Syndrome Associated With Sickle Cell
Disease: A Rare Report of a Common Case.
PMID- 28703373
TI - How to Shoot the Parachute-Minimally Invasive Ventricular Assist Device Surgery
in a Patient Wearing All Existing Cardiologically Available Interventions.
PMID- 28703374
TI - Outcome Improvement for Hypothermic Machine Perfusion Versus Cold Storage for
Kidneys From Cardiac Death Donors.
AB - Organ shortage has led to an increased use of kidneys from cardiac death donors
(DCDs), but controversies about the methods of organ preservation still exist.
This study aims to compare the effect of machine perfusion (MP) and cold storage
(CS) in protecting kidneys harvested from DCDs. 141 kidney pairs from DCDs
between July 2010 and July 2015 were included in this randomized controlled
study. One kidney from each donor was randomly assigned to MP and the
contralateral kidney was assigned to CS. Delayed graft function (DGF) rate,
resistance index of renal arteries, early renal function, and survival rates were
used to estimate the effect of preservation. The results showed that MP decreased
the rate of DGF from 33.3 to 22.0% (P = 0.033). Ultrasound of the kidneys within
48 h after transplantation showed that the resistance index of renal main artery
(0.673 +/- 0.063 vs. 0.793 +/- 0.124, P < 0.001), sub segmental artery (0.66 +/-
0.062 vs. 0.764 +/- 0.077, P < 0.001) and interlobular artery (0.648 +/- 0.056
vs. 0.745 +/- 0.111, P = 0.023) were all significantly lower in the MP group than
those in the CS group. Furthermore, compared to the CS group, in the first 7 days
following transplantation, the median urine volume was significantly higher (4080
mL vs. 3000 mL, P = 0.047) in kidneys sustained using MP and the median serum
creatinine was remarkably lower (180 umol/L vs. 390 umol/L, P = 0.024). More
importantly, MP group had higher 1- and 3-year graft survival rates (98% vs. 93%,
P = 0.026; 93% vs. 82%, P = 0.036, respectively). Hypothermic MP improved the
outcomes of DCD kidney transplantation.
PMID- 28703375
TI - A Combined 1 H/6 Li NMR DOSY Strategy Finally Uncovers the Structure of
Isopropyllithium in THF.
AB - Despite its common use in synthesis, the structure of isopropylliyhium in THF has
never been determined, a dimer being generally proposed but not supported. This
paper fills this data gap through a sophisticated NMR study that shows that, in
THF at low-temperature, isopropyllithium is in the form of a 1:2 mixture of a
trisolvated monomer and a disolvated dimer in equilibrium. The presence of the
monomer, never evoked before, together with a hypo-solvation of the dimer hinted
by DFT calculations, provides a rational explanation to the remarkable reactivity
of this organolithium reagent in ethereal solvents.
PMID- 28703376
TI - Comparison of HER2 testing among laboratories: Our experience with review cases
retested at Moffitt Cancer Center in a two-year period.
AB - Determination of human epidermal receptor protein-2 (HER2) is a crucial step in
the treatment of patients diagnosed with invasive breast carcinoma. HER2 status
is an independent clinical prognostic factor and a predictive factor of tumor
response to chemotherapeutic agents such as trastuzumab. Accurate testing is
necessary to offer adequate therapy to patients. To evaluate the variation in
HER2 testing results, we analyzed our data from review cases in which HER2
testing was repeated at our institution from January 2013 to December 2014. For
the study, the reason for repeating the test, the testing methodology used, and
the tests results were collected. Concordance between outside and in-house HER2
results was compared. Discrepancies were classified as major and minor. A total
of 173 cases were retested during this period. One-hundred and twenty-eight cases
met the inclusion criteria. Sixteen cases were originally tested at large
reference laboratories and two in international laboratories. In the 110
remaining cases, the test was performed at small community laboratories or the
testing facility was not available. Forty-one (32%) discrepancies were
identified. Of these, 15 (12% of 128 total) were major and 26 (20% of 128 total)
were considered minor discrepancies. Our study confirms that significant
discrepancies in HER2 results persist even after stricter and well-developed
testing guidelines have been embraced.
PMID- 28703377
TI - Protective effect of moisturizers on photoaging.
PMID- 28703378
TI - Improvement of drought tolerance by overexpressing MdATG18a is mediated by
modified antioxidant system and activated autophagy in transgenic apple.
AB - Autophagy is a major and conserved pathway for delivering and recycling unwanted
proteins or damaged organelles to be degraded in the vacuoles. AuTophaGy-related
(ATG) protein 18a has been established as one of the essential components for
autophagy occurrence in Arabidopsis thaliana. We previously cloned the ATG18a
homolog from Malus domestica (MdATG18a) and monitored its responsiveness to
various abiotic stresses at the transcriptional level. However, it is still
unclear what its function is under abiotic stress in apple. Here, we found that
heterologous expression of MdATG18a in tomato plants markedly enhanced their
tolerance to drought. Overexpression (OE) of that gene in apple plants improved
their drought tolerance as well. Under drought conditions, the photosynthesis
rate and antioxidant capacity were significantly elevated in OE lines when
compared with the untransformed wild type (WT). Transcript levels of other
important apple ATG genes were more strongly up-regulated in transgenic MdATG18a
OE lines than in the WT. The percentage of insoluble protein in proportion to
total protein was lower and less oxidized protein accumulated in the OE lines
than in the WT under drought stress. This was probably due to more autophagosomes
being formed in the former. These results demonstrate that overexpression of
MdATG18a in apple plants enhances their tolerance to drought stress, probably
because of greater autophagosome production and a higher frequency of autophagy.
Those processes help degrade protein aggregation and limit the oxidation damage,
thereby suggesting that autophagy plays important roles in the drought response.
PMID- 28703379
TI - Stressful life events and posttraumatic growth among police officers: A cross
sectional study.
AB - Police officers often continue to face numerous threats and stressors in the
aftermath of a disaster. To date, posttraumatic growth (PTG) has been studied
primarily in the context of significant trauma; thus, it is not known whether
stressful life events are associated with PTG. This study investigated the
development of PTG among 113 police officers working in the New Orleans area
following Hurricane Katrina. Hierarchical regression was used to evaluate if
gratitude, social support, and satisfaction with life moderated the relationship
between stressful life events (as measured by the total life stress score) and
PTG, after adjustment for age, sex, race, level of involvement in Hurricane
Katrina, and alcohol intake. Results indicate that stressful life events are
independently associated with PTG. Gratitude, satisfaction with life, and social
support were seen to moderate this relationship; as stressful life events
increased so too did PTG-particularly among officers with higher levels of
gratitude (B = 0.002, p <= .05), satisfaction with life (B = 0.002, p <= .05),
and social support (B = 0.001, p <= .05). These findings suggest that promoting
satisfaction with life, interpersonal support, and gratitude may be beneficial to
those who are regularly at risk of trauma exposure.
PMID- 28703380
TI - Chemical Characterization, Antileishmanial Activity, and Cytotoxicity Effects of
the Essential Oil from Leaves of Pluchea carolinensis (Jacq.) G. Don.
(Asteraceae).
AB - Current strategies to control leishmaniasis are mainly based on chemotherapy.
However, none of the available drugs can be considered to be ideal to treat this
disease. Because of the hydrophobic nature and bioactivities of their components,
essential oils (EOs) can be considered as important sources for developing agents
against intracellular pathogens, such as Leishmania parasites. In this study, we
report the chemical characterization, antileishmanial activities, and
cytotoxicity effect of the EO from Pluchea carolinensis (Jacq.) G. Don.
(Asteraceae). Chemical analysis revealed that EO from aerial part from P.
carolinensis is composed of 44 compounds. The main component was selin-11-en
4alpha-ol, which made up 51.0%. In vitro antileishmanial studies showed that P.
carolinensis EO inhibited the growth of promastigotes (IC50 = 24.7 +/- 7.1
MUg/mL) and amastigotes (IC50 = 6.2 +/- 0.1 MUg/mL) of Leishmania amazonensis,
while cytotoxicity evaluation revealed fivefold higher values than those for the
parasites. In a model of experimental cutaneous leishmaniasis in BALB/c mice,
five doses of EO at 30 mg/kg by intralesional route demonstrated smaller lesion
size and parasite burden (p < 0.05) compared with animals treated with
Glucantime(r) and untreated mice. In conclusion, in vitro and in vivo results
showed the potentialities of EO from P. carolinensis with the future possibility
of a new alternative in the treatment for leishmaniasis. Copyright (c) 2017 John
Wiley & Sons, Ltd.
PMID- 28703381
TI - Enhancing image contrast of carbon nanotubes on cellular background using helium
ion microscope by varying helium ion fluence.
AB - Carbon nanotubes (CNTs) have become an important nano entity for biomedical
applications. Conventional methods of their imaging, often cannot be applied in
biological samples due to an inadequate spatial resolution or poor contrast
between the CNTs and the biological sample. Here we report a unique and effective
detection method, which uses differences in conductivities of carbon nanotubes
and HeLa cells. The technique involves the use of a helium ion microscope to
image the sample with the surface charging artefacts created by the He+ and
neutralised by electron flood gun. This enables us to obtain a few nanometre
resolution images of CNTs in HeLa Cells with high contrast, which was achieved by
tailoring the He+ fluence. Charging artefacts can be efficiently removed for
conductive CNTs by a low amount of electrons, the fluence of which is not
adequate to discharge the cell surface, resulting in high image contrast. Thus,
this technique enables rapid detection of any conducting nano structures on
insulating cellular background even in large fields of view and fine spatial
resolution. The technique demonstrated has wider applications for researchers
seeking enhanced contrast and high-resolution imaging of any conducting entity in
a biological matrix - a commonly encountered issue of importance in drug
delivery, tissue engineering and toxicological studies.
PMID- 28703382
TI - Current treatments of acne: Medications, lights, lasers, and a novel 650-MUs 1064
nm Nd: YAG laser.
AB - The treatment of acne, especially severe acne, remains a challenge to
dermatologists. Therapies include retinoids, antibiotics, hormones, lights,
lasers, and various combinations of these modalities. Acne is currently
considered a chronic rather than an adolescent condition. The appropriate
treatment depends on the patient and the severity of disease. The purpose of this
study was to review current therapies for acne of all severities and to introduce
the 650-MUs 1064-nm laser for the treatment of acne.
PMID- 28703383
TI - Implementation of evidence-based treatments for borderline personality disorder:
The impact of organizational changes on treatment outcome of mentalization-based
treatment.
AB - The quality of implementation of evidence-based treatment programs for borderline
personality disorder (BPD) in routine clinical care is a neglected issue. The
first aim of this mixed-method naturalistic study was to explore the impact of
organizational changes on treatment effectiveness of a day-hospital programme of
mentalization-based treatment. Consecutively referred BPD patients were divided
into a pre-reorganization cohort (PRE-REORG) and a cohort during reorganization
(REORG). Psychiatric symptoms (Brief Symptom Inventory) and personality
functioning (Severity Indices of Personality Problems-118) before treatment and
at 18- and 36-month follow-up were compared using multilevel modelling. Effect
sizes in the PRE-REORG cohort were approximately twice as large at 18 months (PRE
REORG: range 0.81-1.22; REORG: range 0.03-0.71) and three times as large at 36
months (PRE-REORG: range 0.81-1.80; REORG: range 0.27-0.81). The quantitative
results of this study suggest that even when mentalization-based treatment is
successfully implemented and the structure of the programme remains intact, major
organizational changes may have a considerable impact on its effectiveness.
Second, we aimed to explore the impact of the reorganization on adherence at
organizational, team and therapist level. The qualitative results of this study
indicate that the organizational changes were negatively related to adherence to
the treatment model at organizational, team and therapist level, which in turn
was associated with a decrease in treatment effectiveness. The implications of
these findings for the implementation of effective treatments for BPD in routine
clinical practice are discussed. Copyright (c) 2017 John Wiley & Sons, Ltd.
PMID- 28703384
TI - Is bigger better? The relationship between size and reproduction in female Asian
elephants.
AB - The limited availability of resources is predicted to impose trade-offs between
growth, reproduction and self-maintenance in animals. However, although some
studies have shown that early reproduction suppresses growth, reproduction
positively correlates with size in others. We use detailed records from a large
population of semi-captive elephants in Myanmar to assess the relationships
between size (height and weight), reproduction and survival in female Asian
elephants, a species characterized by slow, costly life history. Although female
height gain during the growth period overlapped little with reproductive onset in
the population, there was large variation in age at first reproduction and only
81% of final weight had been reached by peak age of reproduction at the
population level (19 years). Those females beginning reproduction early tended to
be taller and lighter later in life, although these trends were not significant.
We found that taller females were more likely to have reproduced by a given age,
but such effects diminished with age, suggesting there may be a size threshold to
reproduction which is especially important in young females. Because size was not
linked with female survival during reproductive ages, the diminishing effect of
height on reproduction with age is unlikely to be due to biased survival of
larger females. We conclude that although reproduction may not always impose
significant costs on growth, height may be a limiting factor to reproduction in
young female Asian elephants, which could have important implications considering
their birth rates are low and peak reproduction is young - 19 years in this
population.
PMID- 28703385
TI - Arsenite induces DNA damage via mitochondrial ROS and induction of mitochondrial
permeability transition.
AB - Arsenite is an established DNA-damaging agent and human carcinogen. We initially
selected conditions in which the metalloid causes DNA strand scission in the
absence of detectable apoptotic DNA degradation in U937 cells. This response was
suppressed by catalase and by treatments (rotenone and ascorbic acid), or
manipulations (respiration-deficient phenotype), preventing the mitochondrial
formation of O2-. ( mitoO2-.). MitoO2-., and its dismutation product, H2 O2 , are
therefore critically involved in the arsenite-dependent DNA-damaging response. We
then established a link between mitoO2-./H2 O2 and mitochondrial permeability
transition (MPT), and found that this second event also promoted the formation of
DNA-damaging species. As a consequence, the DNA damage induced by arsenite, in
addition to being abolished by the aforementioned treatments/manipulations, was
also significantly reduced by the MPT inhibitor cyclosporin A (CsA). A CsA
sensitive induction of p53 mRNA expression was also detected. Finally, evidence
of CsA-sensitive DNA strand scission was also obtained in MCF-7, HT22, and NCTC
2544 cells. MitoO2-./H2 O2 therefore directly mediates DNA damage induced by
arsenite and indirectly promotes the formation of additional DNA-damaging species
via the induction of MPT. (c) 2017 BioFactors, 43(5):673-684, 2017.
PMID- 28703386
TI - High-resolution cone-beam computed tomography for assessment of bone invasion in
oral cancer: Comparison with conventional computed tomography.
AB - BACKGROUND: Radiologic assessment of mandibular bone invasion is critical in
evaluating the extent of bone resection required in patients with oral cancer.
There are a few reports of improved sensitivity with cone-beam CT (CBCT) over
conventional CT. METHODS: A prospective cohort study of patients with oral
squamous cell carcinomas adjacent to the mandible requiring marginal or segmental
mandibular resection was performed. Patients were treated based on clinical
assessment and conventional cross-sectional imaging. Patients and surgeons were
blinded to the results of CBCT performed preoperatively. Pathologic examination
served as the gold standard. RESULTS: Forty-five patients were included in the
study. Thirty-three percent of the patients underwent segmental mandibulectomy
and 37% had bone invasion. The sensitivity and specificity of CBCT were 91% and
60%, respectively, compared to 86% and 68% for CT with bone windows. CONCLUSION:
A CBCT offers marginally improved sensitivity at the cost of reduced specificity
for assessment of bone invasion compared to CT.
PMID- 28703387
TI - One-stage muscle-sparing breast reconstruction in elderly patients: A new tool
for retaining excellent quality of life.
AB - More than 50% of breast cancer care occurs in elderly but women aged 65 and over
generally have lower breast reconstruction (BR) rates. In medical literature, few
papers focused on BR in elderly patients and usually the reported techniques are
multisteps such as expander-implant reconstruction, local, and free flaps. We
present a one-stage reconstruction technique employed in elderly patients: muscle
sparing immediate BR with subcutaneous implant and Braxon acellular dermal
matrix. We prove the feasibility and safety of the technique and believe that
this new procedure could represent a potential benefit in elderly BR.
PMID- 28703388
TI - Stoichiometric and Catalytic C-C and C-H Bond Formation with B(C6 F5 )3 via
Cationic Intermediates.
AB - This work showcases a new catalytic cyclization reaction using a highly Lewis
acidic borane with concomitant C-H or C-C bond formation. The activation of
alkyne-containing substrates with B(C6 F5 )3 enabled the first catalytic
intramolecular cyclizations of carboxylic acid substrates using this Lewis acid.
In addition, intramolecular cyclizations of esters enable C-C bond formation as
catalytic B(C6 F5 )3 can be used to effect formal 1,5-alkyl migrations from the
ester functional groups to unsaturated carbon-carbon frameworks. This metal-free
method was used for the catalytic formation of complex dihydropyrones and
isocoumarins in very good yields under relatively mild conditions with excellent
atom efficiency.
PMID- 28703389
TI - Lipid profiling of complex biological mixtures by liquid chromatography/mass
spectrometry using a novel scanning quadrupole data-independent acquisition
strategy.
AB - RATIONALE: A novel data-independent acquisition method is detailed that
incorporates a scanning quadrupole in front of an orthogonal acceleration time-of
flight (TOF) mass analyser. This approach is described and the attributes are
compared and contrasted to other DIA approaches. METHODS: Specific application of
the method to both targeted and untargeted lipidomic identification strategies is
discussed, with data from both shotgun and LC separated lipidomics experiments
presented. RESULTS: The benefits of the fast quadrupole scanning technique are
highlighted, and include improvements in speed and specificity for complex
mixtures providing high quality qualitative and quantitative data. CONCLUSIONS:
In particular the high specificity afforded by the scanning quadrupole improves
qualitative information for lipid identification.
PMID- 28703390
TI - Physiotherapist-led suprascapular nerve blocks for persistent shoulder pain:
Evaluation of a new service in the UK.
AB - INTRODUCTION: This service evaluation explored and reported findings from a new
physiotherapist-led service offering suprascapular nerve blocks (SSNBs) to
patients with persistent shoulder pain. METHODS: We collected data before the
SSNB injection and at the 6-weeks and 6-month follow-up from consecutive patients
with persistent shoulder pain being treated by physiotherapists or an
anaesthetist. Outcomes were patient-reported pain (numerical rating scale [NRS 0
to 10]), patient-specific functional score (PSFS) and health-related quality of
life [the EuroQol five dimensions questionnaire (EQ5D-5 L)]. Exploratory analyses
compared baseline and follow-up scores within each clinician delivery group
(physiotherapists, anaesthetist). RESULTS: Forty patients (mean age 57 years
[standard deviation {SD} 12]; 63% female) received an SSNB from a
physiotherapist, eight patients (mean age 59 years [SD 11]; female 88%) received
an SSNB from an anaesthetist. At the 6-week follow-up, the physiotherapy group
showed a mean reduction in pain (on the NRS): 2.2 (95% confidence interval [CI]
1.3 to 3.0) and an improvement in function (on the PSFS): -1.3 (95% CI -1.9 to
0.4). Similar changes were found in those treated by the anaesthetist (pain: 1.3
[95% CI -1.18 to 3.80]; function: -1.4 (95% CI -3.18 to 0.35]). Very small
changes, that were not statistically significant, were found in EQ5D-5 L scores.
At the 6-month follow-up, the mean reduction in pain (NRS) was maintained at 2.0
(95% CI 0.99 to 2.95) for the physiotherapy group. CONCLUSION: The results
provide early, exploratory evidence that patients with persistent shoulder pain
treated by physiotherapists using palpation-guided SSNBs achieve clinically
important changes in pain and function in the short and medium term.
PMID- 28703391
TI - Multi-gene phylogenetic analysis reveals that shochu-fermenting Saccharomyces
cerevisiae strains form a distinct sub-clade of the Japanese sake cluster.
AB - Shochu is a traditional Japanese distilled spirit. The formation of the
distinguishing flavour of shochu produced in individual distilleries is
attributed to putative indigenous yeast strains. In this study, we performed the
first (to our knowledge) phylogenetic classification of shochu strains based on
nucleotide gene sequences. We performed phylogenetic classification of 21
putative indigenous shochu yeast strains isolated from 11 distilleries. All of
these strains were shown or confirmed to be Saccharomyces cerevisiae, sharing
species identification with 34 known S. cerevisiae strains (including commonly
used shochu, sake, ale, whisky, bakery, bioethanol and laboratory yeast strains
and clinical isolate) that were tested in parallel. Our analysis used five genes
that reflect genome-level phylogeny for the strain-level classification. In a
first step, we demonstrated that partial regions of the ZAP1, THI7, PXL1, YRR1
and GLG1 genes were sufficient to reproduce previous sub-species classifications.
In a second step, these five analysed regions from each of 25 strains (four
commonly used shochu strains and the 21 putative indigenous shochu strains) were
concatenated and used to generate a phylogenetic tree. Further analysis revealed
that the putative indigenous shochu yeast strains form a monophyletic group that
includes both the shochu yeasts and a subset of the sake group strains; this
cluster is a sister group to other sake yeast strains, together comprising a sake
shochu group. Differences among shochu strains were small, suggesting that it may
be possible to correlate subtle phenotypic differences among shochu flavours with
specific differences in genome sequences. Copyright (c) 2017 John Wiley & Sons,
Ltd.
PMID- 28703392
TI - A comparison between vitamin K antagonists and new oral anticoagulants.
PMID- 28703393
TI - Serological diagnostics in the detection of IgG autoantibodies against human
collagen VII in epidermolysis bullosa acquisita: a multicentre analysis.
AB - BACKGROUND: Epidermolysis bullosa acquisita (EBA) is a rare, potentially
devastating autoimmune disease of the skin. IgG autoantibodies directed against
type VII collagen (Col7), the major component of anchoring fibrils, induce skin
fragility leading to cutaneous and mucocutaneous blister formation, which is
mostly of a scarring phenotype. Thus, powerful and reproducible diagnostic assays
are critical to establish the diagnosis of EBA early to avoid irreversible
sequelae. OBJECTIVES: The present international, retrospective multicentre study
included a large cohort of patients with EBA and evaluated the diagnostic power
of four different diagnostic assays for the detection of anti-Col7 IgG
autoantibodies. METHODS: Overall, 95 EBA sera and 200 control sera consisting of
100 bullous pemphigoid sera, 50 pemphigus vulgaris sera and 50 sera of healthy
controls were tested for anti-Col7 IgG autoantibodies using indirect
immunofluorescence (IIF), two commercial enzyme-linked immunosorbent assay
(ELISA) systems and Western blot (WB) analysis. EBA sera were taken from patients
with positive direct immunofluorescence and IgG reactivity in at least one of the
immunoserological assays (IIF, ELISA, WB). RESULTS: A Col7-NC1/NC2 ELISA (MBL,
Nagoya, Japan) showed the highest sensitivity (97.9%), followed by a Col7-NC1
ELISA (Euroimmun, Lubeck, Germany) (89.5%), WB with Col7-NC1 (85.3%), and IIF on
saline-split human skin (74.7%). The specificities of both ELISA systems were
comparable (NC1 98.7%, NC1/NC2 99.3%). Furthermore, WB was more sensitive than
IIF, which was more specific. CONCLUSIONS: The two commercially available ELISA
systems allow for a highly sensitive and specific diagnosis of EBA. The
sensitivity of the Col7-NC1/NC2 ELISA is significantly higher compared with the
ELISA based on the Col7-NC1 domain only.
PMID- 28703394
TI - Priorities and challenges for a palliative approach to care for rural indigenous
populations: A scoping review.
AB - We carried out a scoping review to identify key priorities and challenges
relevant to rural Indigenous palliative care stated in existing literature. Our
scoping review activities followed Arskey and O'Malley's principles for
conducting a scoping review. We included peer-reviewed literature from MEDLINE,
CINAHL and EMBASE that included a discussion of Indigenous populations,
palliative care, and rural settings, and did not use date limits. The literature
search was conducted in April 2016, and the retrieved literature was screened for
relevance and appropriateness April 2016-March of 2017. In addition to the
academic literature, a scan of the grey literature was conducted in March 2017.
The retrieved grey literature was screened for relevance and reviewed by a team
from a provincial health authority serving Indigenous peoples to ensure relevance
in a rural BC setting. Once reviewed for relevance and appropriateness, we added
four reports to supplement our analysis. Ultimately, 44 peer-reviewed articles
and 4 pieces of grey literature met our inclusion criteria and were included in
the review. Our analysis revealed several challenges and priorities relevant to
rural Indigenous palliative care. Key challenges included: (i) environmental and
contextual issues; (ii) institutional barriers; and (iii) interpersonal dynamics
challenging client/clinician interactions. Priorities included: (i) family
connections throughout the dying process; (ii) building local capacity for
palliative care to provide more relevant and culturally appropriate care; and
(iii) flexibility and multi-sectoral partnerships to address the complexity of
day-to-day needs for patients/families. These findings point to several areas for
change and action that can improve the relevance, access and comprehensiveness of
palliative care programming for rural Indigenous communities in Canada and
elsewhere. Taking into account of the diversity and unique strengths of each
Indigenous community will be vital in developing sustainable and meaningful
change.
PMID- 28703395
TI - New perspectives on study designs for evaluating neuroprotection in Parkinson's
disease.
PMID- 28703396
TI - On the Relation Between Marr's Levels: A Response to Blokpoel (2017).
AB - Blokpoel reminds us of the importance of consistency of function across Marr's
levels, but we argue that the approach to ensuring consistency that he advocates
a strict relation through exact implementation of the higher level function at
the lower level-is unnecessarily restrictive. We show that it forces
overcomplication of the computational level (by requiring it to incorporate
concerns from lower levels) and results in the sacrifice of the distinct
responsibilities associated with each level. We propose an alternative, no less
rigorous, potential characterization of the relation between levels.
PMID- 28703397
TI - Tai chi for mild cognitive impairment: a systematic review.
PMID- 28703398
TI - Tissue dynamics and regenerative outcome in two resorbable non-cross-linked
collagen membranes for guided bone regeneration: A preclinical molecular and
histological study in vivo.
AB - OBJECTIVES: To investigate the molecular and structural patterns of bone healing
during guided bone regeneration (GBR), comparing two resorbable non-cross-linked
collagen membranes. MATERIALS AND METHODS: Trabecular bone defects in rat femurs
were filled with deproteinized bovine bone (DBB) and covered with either a
membrane comprising collagen and elastin (CXP) or collagen (BG). Samples were
harvested after 3 and 21 days for histology/histomorphometry and gene expression
analysis. Gene expression analysis was performed on the membrane (at 3 days) and
the underlying defect compartment (at 3 and 21 days). RESULTS: At the total
defect level, no differences in bone area percentage were found between the CXP
and BG. When evaluating the central area of the defect, a higher percentage of de
novo bone formation was seen for the CXP membrane (34.9%) compared to BG (15.5%)
at 21 days (p = .01). Gene expression analysis revealed higher expression of bone
morphogenetic protein-2 (Bmp2) in the membrane compartment at 3 days in the BG
group. By contrast, higher Bmp2 expression was found in the defect compartment
treated with the CXP membrane, both at 3 and 21 days. A significant temporal
increase (from 3 to 21 days) in the remodeling activity, cathepsin K (Catk) and
calcitonin receptor (Calcr), was found in the CXP group. Molecular analysis
demonstrated expression of several growth factors and cytokines in the membrane
compartment irrespective of the membrane type. Bmp2 expression in the membrane
correlated positively with Bmp2 expression in the defect, whereas fibroblast
growth factor-2 (Fgf2) expression in the membrane correlated positively with
inflammatory cytokines, tumor necrosis factor-alpha (Tnfa) and interleukin-6
(Il6) in the defect. CONCLUSIONS: The results provide histological and molecular
evidence that different resorbable collagen membranes contribute differently to
the GBR healing process. In the BG group, bone formation was primarily localized
to the peripheral part of the defect. By contrast, the CXP group demonstrated
significantly higher de novo bone formation in the central portion of the defect.
This increase in bone formation was reflected by triggered expression of potent
osteogenic growth factor, Bmp2, in the defect. These findings suggest that the
CXP membrane may have a more active role in regulating the bone healing dynamics.
PMID- 28703399
TI - CE and nanomaterials - Part II: Nanomaterials in CE.
AB - The scope of this two-part review is to summarize publications dealing with CE
and nanomaterials together. This topic can be viewed from two broad perspectives,
and this article is trying to highlight these two approaches: (i) CE of
nanomaterials, and (ii) nanomaterials in CE. The second part aims at
summarization of publications dealing with application of nanomaterials for
enhancement of CE performance either in terms of increasing the separation
resolution or for improvement of the detection. To increase the resolution,
nanomaterials are employed as either surface modification of the capillary wall
forming open tubular column or as additives to the separation electrolyte
resulting in a pseudostationary phase. Moreover, nanomaterials have proven to be
very beneficial for increasing also the sensitivity of detection employed in CE
or even they enable the detection (e.g., fluorescent tags of nonfluorescent
molecules).
PMID- 28703400
TI - Mitochondria-targeted antioxidant SkQ1 improves spermatogenesis in Immp2l mutant
mice.
AB - Previous studies have confirmed that spermatogenesis in homozygous Immp2l mutant
male mice was normal at the age of 6 months, but was significantly abnormal at
the age of 13 months. Meanwhile, oxidative stress is reported to be involved in
spermatogenic impairment in old mutant mice. However, it is unclear whether
antioxidant treatment is a suitable intervention for improving spermatogenesis in
old mutant mice. This study sought to investigate the effect of mitochondria
targeted antioxidant SkQ1 on spermatogenesis in homozygous Immp2l mutant mice.
Immp2l mutant mice were treated with the mitochondria-targeted antioxidant SkQ1
from the age of 6 weeks until 13 months. SkQ1 treatment significantly improved
spermatogenesis in old Immp2 l mutant mice. Moreover, SkQ1 treatment improved the
morphology of testicular seminiferous tubules, significantly reduced the
apoptosis of germ cells and increased the level of GPX4 expression in old Immp2 l
mutant mice. In conclusion, our data suggest that the mitochondria-targeted
antioxidant SkQ1 is effective in improving spermatogenesis in Immp2 l mutant mice
and might be used for the treatment of male infertility.
PMID- 28703401
TI - Adsorption of Protein-Bound Uremic Toxins Through Direct Hemoperfusion With
Hexadecyl-Immobilized Cellulose Beads in Patients Undergoing Hemodialysis.
AB - An accumulation of protein-bound uremic toxins (PBUTs) is one of major reasons
for development of uremia-related complications. We examined the PBUT removal
ability of a hexadecyl-immobilized cellulose bead (HICB)-containing column for
patients undergoing hemodialysis. Adsorption of indoxyl sulfate (IS), a
representative PBUT, to HICBs was examined in vitro. The HICB column was used in
patients undergoing hemodialysis for direct hemoperfusion with a regular
hemodialyzer. The serum IS, indole acetic acid (IAA), phenyl sulfate (PhS), and p
cresyl sulfate (PCS) levels were measured before and after passing the column.
HICBs adsorbed protein-free (free) IS in a dose- and time-dependent manner in
vitro (55.4 +/- 1.4% adsorption of 1 millimolar, 251 ug/mL, IS for 1 h). In
clinical studies, passing the HICB-containing column decreased the serum level of
free IS, IAA, PhS, and PCS levels significantly (by 34.4 +/- 30.0%, 34.8 +/-
25.4%, 28.4 +/- 18.0%, and 34.9 +/- 22.1%, respectively), but not protein-bound
toxins in maintenance hemodialysis patients. HICBs absorbed some amount of free
PBUTs, but the clinical trial to use HICB column did not show effect to reduce
serum PBUTs level in hemodialysis patients. Adsorption treatment by means of
direct hemoperfusion with regular hemodialysis may become an attractive blood
purification treatment to increase PBUT removal when more effective materials to
adsorb PBUTs selectively will be developed.
PMID- 28703402
TI - Laparoscopic surgery to remove a cage that migrated to the retroperitoneal space
during posterior lumbar interbody fusion: A case report.
AB - INTRODUCTION: Cage migration into the retroperitoneal space during posterior
lumbar interbody fusion rarely occurs. Here, we report a patient who underwent
laparoscopic surgery to remove a migrated cage from the retroperitoneal space.
CASE PRESENTATION: A 76-year-old woman had a cage that had migrated into the
retroperitoneal space during posterior lumbar interbody fusion. On abdominal CT,
the migrated cage appeared at the front of the promontorium, just below the
aortic and vena caval bifurcations. One day later, the patient underwent
laparoscopic surgery using intraoperative fluoroscopy to extract the migrated
cage. The patient's postoperative course was uneventful, and she was discharged
on the fifth postoperative day. DISCUSSION: A cage that migrates during posterior
lumbar interbody fusion can have serious consequences. In cases where the patient
remains in stable condition, laparoscopic surgery is a useful and suitable method
for removing the cage from the retroperitoneal space.
PMID- 28703403
TI - Utilizing pretreatment and fungal incubation to enhance the nutritional value of
canola meal.
AB - AIMS: The objective of this study was to determine the optimal pretreatment and
fungal strain to reduce glucosinolates (GLS), fibre and residual sugars while
increasing the nutritional value of canola meal. METHODS AND RESULTS: Submerged
incubation conditions were used to evaluate four pretreatment methods (extrusion,
hot water cook, dilute acid and dilute alkali) and three fungal cultures
(Aureobasidium pullulans Y-2311-1, Fusarium venenatum NRRL-26139 and Trichoderma
reesei NRRL-3653) in hexane-extracted (HE) and cold-pressed (CP) canola meal.
CONCLUSIONS: The combination of extrusion pretreatment followed by incubation
with T. reesei resulted in the greatest overall improvement to HE canola meal,
increasing protein to 51.5%, while reducing NDF, GLS and residual sugars to
18.6%, 17.2 MUmol l-1 g-1 and 5% w/w, respectively. Extrusion pretreatment and
incubation with F. venenatum performed the best with CP canola meal, resulting in
54.4% protein while reducing NDF, GLS and residual sugars to 11.6%, 6.7 MUmol l-1
g-1 and 3.8% w/w respectively. SIGNIFICANCE AND IMPACT OF THE STUDY: The work is
significant in that it provides a method of reducing GLS (up to 98%) and neutral
detergent fibre (up to 65%) while increasing the protein content (up to 45%) of
canola meal. This novel pretreatment and submerged incubation process could be
used to produce a canola product with higher nutritional value for livestock
consumption.
PMID- 28703404
TI - Construction of Morphan Derivatives by Nitroso-Ene Cyclization: Mechanistic
Insight and Total Synthesis of (+/-)-Kopsone.
AB - A type II nitroso-ene cyclization was developed for the construction of morphan
derivatives with good functional-group tolerance. DFT calculations revealed that
the nitroso-ene reaction proceeds in a stepwise manner involving diradical or
zwitterionic intermediates. The rate-determining step is C-N bond formation,
followed by a rapid hydrogen-transfer step with a chair-conformation transition
state. The current approach was also successfully applied in the first total
synthesis of (+/-)-kopsone, a highly strained yet simple morphan-type alkaloid
isolated from Kopsia macrophylla.
PMID- 28703405
TI - Rational design of biosafe crop resistance to a range of nematodes using RNA
interference.
AB - Double-stranded RNA (dsRNA) molecules targeting two genes have been identified
that suppress economically important parasitic nematode species of banana.
Proteasomal alpha subunit 4 (pas-4) and Actin-4 (act-4) were identified from a
survey of sequence databases and cloned sequences for genes conserved across four
pests of banana, Radopholus similis, Pratylenchus coffeae, Meloidogyne incognita
and Helicotylenchus multicinctus. These four species were targeted with dsRNAs
containing exact 21 nucleotide matches to the conserved regions. Potential off
target effects were limited by comparison with Caenorhabditis, Drosophila, rat,
rice and Arabidopsis genomes. In vitro act-4 dsRNA treatment of R. similis
suppressed target gene expression by 2.3-fold, nematode locomotion by 66 +/- 4%
and nematode multiplication on carrot discs by 49 +/- 5%. The best transgenic
carrot hairy root lines expressing act-4 or pas-4 dsRNA reduced transcript
message abundance of target genes in R. similis by 7.9-fold and fourfold and
nematode multiplication by 94 +/- 2% and 69 +/- 3%, respectively. The same act-4
and pas-4 lines reduced P. coffeae target transcripts by 1.7- and twofold and
multiplication by 50 +/- 6% and 73 +/- 8%. Multiplication of M. incognita on the
pas-4 lines was reduced by 97 +/- 1% and 99 +/- 1% while target transcript
abundance was suppressed 4.9- and 5.6-fold. There was no detectable RNAi effect
on nontarget nematodes exposed to dsRNAs targeting parasitic nematodes. This work
defines a framework for development of a range of nonprotein defences to provide
broad resistance to pests and pathogens of crops.
PMID- 28703406
TI - Using indocyanine green fluorescent imaging to successfully resect metachronous
regional lymph node recurrence of rectosigmoid cancer.
AB - A 39-year-old female patient underwent anterior resection with locoregional lymph
node dissection for rectosigmoid cancer at another hospital. The procedure
involved transection of the superior rectal artery just below the origin of the
left colic artery. Postoperative diagnosis was stage III B. The patient received
adjuvant chemotherapy with oxaliplatin plus capecitabine for 6 months. Sixteen
months after the operation, PET-CT scans revealed regional lymph node metastases
around the root of the inferior mesenteric artery. The patient was referred to
our hospital with a recurrence of rectosigmoid cancer. We performed laparoscopic
lymph node dissection with real-time indocyanine green fluorescent images
superimposed on color images to prevent intraoperative vascular insufficiency. We
were able to successfully observe the sufficient blood flow in the descending
colon. Postoperative pathological findings showed lymph node recurrence after
initial surgery. She was discharged 7 days after the operation. In the 8 months
since the second operation, the patient has not had any indication of further
recurrence.
PMID- 28703407
TI - Three relapses after a haploidentical transplantation in a pediatric patient:
Cure with no further transplantation.
AB - Isolated extramedullary relapse (EMR) after hematopoietic stem cell
transplantation (HSCT) is a highly fatal condition that creates uncertainty
regarding treatment options. Although certain approaches such as repeat HSCT and
donor lymphocyte infusion are recommended, we report a patient with acute
lymphoblastic leukemia who had three isolated EMRs after HSCT at different
locations and at different times that were responsive to local and systemic
therapies, without the need for a second transplantation.
PMID- 28703408
TI - Electrochemical and piezoelectric monitoring of taurine via electropolymerized
molecularly imprinted films.
AB - A molecularly imprinted electrochemical quartz crystal microbalance (EQCM) sensor
is fabricated here for taurine, a beta-amino acid significant for functioning of
almost all vital organs. The polymeric film of l-methionine was electrochemically
deposited on gold-coated EQCM electrode. Experimental parameters were optimized
for controlling the performance of molecularly imprinted polymer (MIP)-modified
sensor such as ratio of monomer and template, number of electropolymerization
cycles, mass deposited in each cycle, and pH. Thus, fabricated MIP-EQCM sensor
was successfully applied for estimation of taurine in solutions with varying
matrices, such as aqueous, human blood plasma, milk from cow, buffalo, and milk
powder. Under optimized parameters, response of MIP sensor to taurine was
linearly proportional to its concentration with limit of detection as 0.12MUM.
Hence, a highly sensitive and selective piezoelectric sensor for taurine has been
reported here via imprinting approach.
PMID- 28703409
TI - The individual experience of ageing prisoners: systematic review and meta
synthesis through a Good Lives Model framework.
AB - OBJECTIVE: The existing literature on ageing prisoners tends to focus on such
aspects as diagnosis and physical ill-health. In contrast, the experience of
imprisonment from the perspective of ageing prisoners has received less
attention. Grounded in a Good Lives Model theoretical framework, we reviewed and
meta-synthesised literature around their experience of life in prison, its impact
on their wellbeing and how prison services are currently addressing their complex
needs. We further identify potential areas of improvement. METHODS: 1. Systematic
search on Assia, PsycInfo, MedLine, Embase, Web of Science, Google and Gov.uk. 2.
Extraction and categorisation of data on NVivo. 3. Development of themes through
thematic analysis and meta-synthesis. 4. Identification of potential areas of
improvement. RESULTS: We selected 25 studies for our review, of which 13 were
from the USA, seven from the UK, two from Australia and one each from Ireland,
Switzerland and Israel. We identified three themes: The hardship of imprisonment,
addressing health and social care needs, and the route out of prison.
CONCLUSIONS: Ageing prisoners have unique and complex health and social care
needs which, to varying degree across different countries, are mostly unmet.
Promising initiatives to address their needs are emerging, but, at present time,
the overall experience of incarceration for the ageing prisoner is quite poor,
given the inconsistent physical, emotional and social care support offered from
prison intake to release and beyond. Copyright (c) 2017 John Wiley & Sons, Ltd.
PMID- 28703410
TI - Review of some pharmacokinetic and pharmacodynamic properties of anti-infective
medicines administered to the koala (Phascolarctos cinereus).
AB - Although koalas are iconic Australian animals, no pharmacokinetic studies of any
first-line medicines used to treat diseased or injured koalas had been published
prior to 2010. Traditionally, medicine dosages suggested for this species
underwent linear extrapolation from those recommended for domesticated species.
The koala, a specialist folivore whose natural diet consists of almost
exclusively Eucalyptus spp. foliage has anatomical and physiological adaptations
for detoxifying their diet which also affect medicine pharmacokinetic profiles.
This review addresses aspects of medicine absorption, clearance, and other
indices (such as medicine binding to plasma proteins) of
enrofloxacin/marbofloxacin and chloramphenicol used for the systemic treatment of
chlamydiosis, and fluconazole +/- amphotericin, and posaconazole for the
treatment of cryptococcosis. Based on observations from published studies, this
review includes suggestions to improve therapeutic outcomes when administering
medicines to diseased koalas.
PMID- 28703411
TI - Development of the New Zealand White Rabbit Eye: I. Pre- and Postnatal
Development of Eye Tunics.
AB - The New Zealand white (NZW) rabbit has been and is right now regularly utilized
in ophthalmic surgery evaluation. Inside NZW rabbit eye, the visibility of ocular
structures throughout surgical procedure is fantastic. Younger rabbits are used
in different ages for the evaluation of ophthalmic surgery. Complete studies of
ocular development in the NZW rabbits have not been reported previously. The aim
of the present investigation was to describe the major landmarks and the time
course of the pre- and post-natal development of the complete eye tunics of the
NZW rabbit to give a superb model as well as a fruitful area for further
ophthalmological investigations. Serial histological sections of NZW rabbit
prenatal (E13-E28) and post-natal (P1-P14) stages were examined, respectively.
The eye of the NZW rabbit developed in a similar manner to that of the human and
domestic animals eyes; the principal differences were at the time of occurrence
of certain developmental events, absence of pigmentation which represent an
exploited benefit for ophthalmic surgery, remarkable Bowman's membrane at E25,
poor developed ciliary stroma and juvenile retinal layer until P9. In human, the
basic morphogenetic processes of the development of eye tunics are completed
towards the end of the first half of gestation period. However, the latter
represents the beginning stage of the development of eye tunics in the rabbit.
Thus, allowing various extensive ophthalmic researches to be performed.
PMID- 28703412
TI - Fumarate hydratase expression is retained in atypical intradermal smooth muscle
neoplasms and cutaneous leiomyosarcomas.
PMID- 28703413
TI - Modulation of the peri-infarct neurogliovascular function by delayed COX-1
inhibition.
AB - PURPOSE: Stroke is the leading cause of adult disability worldwide. The absence
of more effective interventions in the chronic stage-that most patients stand to
benefit from-reflects uncertainty surrounding mechanisms that govern recovery.
The present work investigated the effects of a novel treatment (selective
cyclooxygenase-1, COX-1, inhibition) in a model of focal ischemia. MATERIALS AND
METHODS: FR122047 (COX-1 inhibitor) was given beginning 7 days following stroke
(cortical microinjection of endothelin-1) in 23 adult male rats. Longitudinal
continuous-arterial-spin-labeling was performed prior to treatment (7 days), and
repeated following treatment (21 days) on a 7T magnetic resonance imaging (MRI)
system to estimate resting perfusion and reactivity to hypercapnia. These in vivo
measurements were buttressed by immunohistochemistry. RESULTS: Stroke caused an
increase in perilesional resting perfusion (peri-/contralesional perfusion ratio
of 170 +/- 10%) and perfusion responses to hypercapnia (180 +/- 10%) at 7 days.
At 21 days, placebo-administered rats showed normalized perilesional perfusion
(100 +/- 20%) but persistent hyperreactivity (190 +/- 20%). Treated animals
exhibited sustained perilesional hyperperfusion (180 +/- 10%). Further,
reactivity lateralization did not persist following treatment (peri- vs.
contralesional reactivity: P = 0.002 at 7 vs. P = 0.2 at 21 days). Hemodynamic
changes were accompanied by neuronal loss, increased endothelial density, and
widespread microglial and astrocytic activation. Moreover, relative to controls,
treated rats showed increased perilesional neuronal survival (22 +/- 1% vs. 14.9
+/- 0.8%, P = 0.02) and decreased microglia/macrophage recruitment (17 +/- 1% vs.
20 +/- 1%, P = 0.05). Finally, perilesional perfusion was correlated with
neuronal survival (slope = 0.14 +/- 0.05; R2 = 0.7, P = 0.03). CONCLUSION: These
findings shed light on the role of COX-1 in chronic ischemic injury and suggest
that delayed selective COX-1 inhibition exerts multiple beneficial effects on the
neurogliovascular unit. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 4 J. MAGN.
RESON. IMAGING 2017;46:505-517.
PMID- 28703414
TI - Impact of pregnancy on observed sex disparities among adults hospitalized with
laboratory-confirmed influenza, FluSurv-NET, 2010-2012.
AB - INTRODUCTION: Previous FluSurv-NET studies found that adult females had a higher
incidence of influenza-associated hospitalizations than males. To identify groups
of women at higher risk than men, we analyzed data from 14 FluSurv-NET sites that
conducted population-based surveillance for laboratory-confirmed influenza
associated hospitalizations among residents of 78 US counties. METHODS: We
analyzed 6292 laboratory-confirmed, geocodable (96%) adult cases collected by
FluSurv-NET during the 2010-12 influenza seasons. We used 2010 US Census and 2008
2012 American Community Survey data to calculate overall age-adjusted and age
group-specific female:male incidence rate ratios (IRR) by race/ethnicity and
census tract-level poverty. We used national 2010 pregnancy rates to estimate
denominators for pregnant women aged 18-49. We calculated male:female IRRs
excluding them and IRRs for pregnant:non-pregnant women. RESULTS: Overall, 55% of
laboratory-confirmed influenza cases were female. Female:male IRRs were highest
for females aged 18-49 of high neighborhood poverty (IRR 1.50, 95% CI 1.30-1.74)
and of Hispanic ethnicity (IRR 1.70, 95% CI 1.34-2.17). These differences
disappeared after excluding pregnant women. Overall, 26% of 1083 hospitalized
females aged 18-49 were pregnant. Pregnant adult females were more likely to have
influenza-associated hospitalizations than their non-pregnant counterparts
(relative risk [RR] 5.86, 95% CI 5.12-6.71), but vaccination levels were similar
(25.5% vs 27.8%). CONCLUSIONS: Overall rates of influenza-associated
hospitalization were not significantly different for men and women after
excluding pregnant women. Among women aged 18-49, pregnancy increased the risk of
influenza-associated hospitalization sixfold but did not increase the likelihood
of vaccination. Improving vaccination rates in pregnant women should be an
influenza vaccination priority.
PMID- 28703415
TI - Nursing diagnoses related to psychiatric adult inpatient care.
AB - AIMS AND OBJECTIVES: To detect the prevalence of NANDA-I diagnoses and possible
relationships between those and patient characteristics such as gender, age,
medical diagnoses and psychiatric specialty/setting. BACKGROUND: There is a lack
on studies about psychiatric inpatient characteristics and possible relationships
among these characteristics with nursing diagnoses. DESIGN: A quantitative
descriptive, cross-sectional, completed data sampling study was performed.
METHODS: The data were collected from the electronic patient record system.
Frequencies for the social-demographic data, the prevalence of the NANDA-I
diagnoses and the explanatory variables were calculated. RESULTS: In total, 410
nursing phenomena were found representing 85 different NANDA-I diagnoses in 312
patients. The NANDA-I diagnosis "Ineffective Coping" was the most frequently
stated diagnosis followed by "Ineffective Health Maintenance," "Hopelessness" and
"Risk for Other-Directed Violence". Men were more frequently affected by the
diagnoses "Ineffective Coping," "Hopelessness," "Risk for Self-Directed
Violence," "Defensive Coping" and "Risk for Suicide," whereas the diagnoses
"Insomnia," "Chronic Confusion," "Chronic Low Self-Esteem" and "Anxiety" were
more common in women. Patients under the age of 45 years were more frequently
affected by "Chronic Low Self-Esteem" and "Anxiety" than older patients.
"Ineffective Coping" was the most prevalent diagnosis by patients with mental
disorders due to psychoactive substance use. Patients with schizophrenia were
primarily affected by the diagnoses "Ineffective Coping," "Impaired Social
Interaction" and "Chronic Low Self-Esteem." CONCLUSIONS: This study demonstrates
the complexity and diversity of nursing care in inpatient psychiatric settings.
Patients' gender, age and psychiatric diagnoses and settings are a key factor for
specific nursing diagnosis. RELEVANCE TO CLINICAL PRACTICE: There are tendencies
for relationships between certain nursing diagnosis and patient characteristics
in psychiatric adult inpatients. This enhances the specific, extended knowledge
for nursing care and its demands in this setting and therefore supports the daily
nursing psychiatric care and its needs.
PMID- 28703417
TI - Dynamic Nuclear Polarization Fast Field Cycling Method for the Selective Study of
Molecular Dynamics in Block Copolymers.
AB - Dynamic nuclear polarization (DNP) is one of the most useful methods to increase
sensitivity in NMR spectroscopy. It is based on the transfer of magnetization
from an electron to the nuclear spin system. Based on previous work that
demonstrated the feasibility of integrating DNP with fast field cycling (FFC)
relaxometry and the possibility to distinguish between different mechanisms, such
as the Overhauser effect (OE) and the solid effect (SE), the first FFC study of
the differential relaxation properties of a copolymer is presented. For this
purpose, concentrated solutions of the polystyrene-block-polybutadiene-block
polystyrene (SBS) triblock copolymer and the corresponding homopolymers were
investigated. T1 -T2 relaxation data are discussed in terms of molecular mobility
and the presence of radicals. The DNP selective data indicate a dominant SE
contribution to the enhancement of the NMR signal for both blocks of the triblock
copolymer and for the homopolymer solutions. The enhancement factors are
different for both polymer types and in the copolymer, which is explained by the
individual 1 H T1 relaxation times and different electron-nucleus coupling
strength. The T1 relaxation dispersion measurements of the SE enhanced signal
were performed, which led to improved signal-to-noise ratios that allowed the
site-specific separation of relaxation times and their dependence on the Larmor
frequency with a higher accuracy.
PMID- 28703416
TI - ABA signalling manipulation suppresses senescence of a leafy vegetable stored at
room temperature.
AB - Postharvest senescence and associated stresses limit the shelf life and
nutritional value of vegetables. Improved understanding of these processes
creates options for better management. After harvest, controlled exposure to
abiotic stresses and/or exogenous phytohormones can enhance nutraceutical,
organoleptic and commercial longevity traits. With leaf senescence, abscisic acid
(ABA) contents progressively rise, but the actual biological functions of this
hormone through senescence still need to be clarified. Postharvest senescence of
detached green cabbage leaves (Brassica oleracea var. capitata) was characterized
under cold (4 degrees C) and room temperature (25 degrees C) storage
conditions. Hormonal profiling of regions of the leaf blade (apical, medial,
basal) revealed a decrease in cytokinins contents during the first days under
both conditions, while ABA only increased at 25 degrees C. Treatments with ABA
and a partial agonist of ABA (pyrabactin) for 8 days did not lead to significant
effects on water and pigment contents, but increased cell integrity and altered 1
aminocyclopropane-1-carboxylic acid (ACC) and cytokinins contents. Transcriptome
analysis showed transcriptional regulation of ABA, cytokinin and ethylene
metabolism and signalling; proteasome components; senescence regulation;
protection of chloroplast functionality and cell homeostasis; and suppression of
defence responses (including glucosinolates and phenylpropanoids metabolism). It
is concluded that increasing the concentration of ABA (or its partial agonist
pyrabactin) from the start of postharvest suppresses senescence of stored leaves,
changes the transcriptional regulation of glucosinolates metabolism and down
regulates biotic stress defence mechanisms. These results suggest a potential for
manipulating ABA signalling for improving postharvest quality of leafy vegetables
stored at ambient temperature.
PMID- 28703418
TI - The medline UK filter: development and validation of a geographic search filter
to retrieve research about the UK from OVID medline.
AB - BACKGROUND: A validated geographic search filter for the retrieval of research
about the United Kingdom (UK) from bibliographic databases had not previously
been published. OBJECTIVES: To develop and validate a geographic search filter to
retrieve research about the UK from OVID medline with high recall and precision.
METHODS: Three gold standard sets of references were generated using the relative
recall method. The sets contained references to studies about the UK which had
informed National Institute for Health and Care Excellence (NICE) guidance. The
first and second sets were used to develop and refine the medline UK filter. The
third set was used to validate the filter. Recall, precision and number-needed-to
read (NNR) were calculated using a case study. RESULTS: The validated medline UK
filter demonstrated 87.6% relative recall against the third gold standard set. In
the case study, the medline UK filter demonstrated 100% recall, 11.4% precision
and a NNR of nine. CONCLUSION: A validated geographic search filter to retrieve
research about the UK with high recall and precision has been developed. The
medline UK filter can be applied to systematic literature searches in OVID
medline for topics with a UK focus.
PMID- 28703419
TI - An autopsy case of Creutzfeldt-Jakob disease with a prion protein gene codon 180
mutation presenting with pathological laughing and an exaggerated startle
reaction.
AB - A 78-year-old Japanese woman presented with slow progressive disorientation and
memory disturbances. Pathological laughing was observed at an early disease stage
and continued for several months. Around the same time, the patient began to
exhibit an exaggerated startle reaction and mild myoclonus. The pathological
laughing and startle reaction disappeared before the patient reached an akinetic
mutism state approximately 16 months after symptom onset. MRI showed extensive
hyperintensity of the cerebral cortex and striatum on diffusion-weighted images,
and swelling in the cerebral cortex on T2-weighted and fluid attenuated inversion
recovery images. A prion protein (PrP) gene analysis revealed a V180I mutation
with methionine homozygosity at codon 129. Neuropathological examination showed
extensive spongiform changes with characteristic various-sized and non-confluent
(VaSNoC) vacuoles in the cerebral neocortex and striatum. Gliosis and
hypertrophic astrocytosis were generally mild in character. Neurons were
relatively preserved in number. We believe that pathological laughing and an
exaggerated startle reaction are possible pathognomonic findings of V180I genetic
Creutzfeldt-Jakob disease. Based on the pathological findings of the present
case, the presence of the VaSNoC-type spongiform changes with relative
preservation of the neurons in the cerebral cortex and a lack of apparent
brainstem involvement are associated at least in part with the pathological
laughing and startle reaction.
PMID- 28703420
TI - Ultrasound Morphology of Polycaprolactone Filler.
AB - Nowadays, cosmetic fillers are widely used and the reports of complications are
rising. Therefore, the possibility to detect and identify noninvasively new
fillers can provide a potent tool for managing complications. The objective of
this study was to assess the ultrasound morphology of polycaprolactone. First,
polycaprolactone was injected into porcine skin and this sonographic morphology
was prospectively compared with the one observed in patients injected with this
filler. On sonography, polycaprolactone shows as hypoechoic deposits that present
multiple bright hyperechoic spots with mini-comet-tail artifact. This morphology
differs from the ultrasound appearance of other common fillers.
PMID- 28703421
TI - Amelioration of oxidative stress using N-acetylcysteine in canine parvoviral
enteritis.
AB - Previously, antioxidants have not been evaluated for treatment of parvoviral
diarrhea in dogs. In this study, antioxidant potential of N-acetylcysteine (NAC)
in dogs infected with canine parvovirus with a nonblinded randomized clinical
trial has been carried out. A total 18 parvo-infected dogs were randomly divided
into two groups: nine parvo-infected dogs were treated with supportive treatment
and nine parvo-infected dogs were treated with NAC along with supportive
treatment. Simultaneously, nine healthy dogs were kept as healthy control. In
parvo-infected dogs, marked hemoconcentration, leucopenia, neutropenia and
oxidative stress were noticed compared to healthy dogs. The NAC treatment
progressively improved the leukocyte, neutrophil, monocyte, and eosinophil counts
over the time in parvovirus-infected dogs compared to dogs that received only
supportive treatment. In addition, NAC treatment significantly improved
glutathione S-transferase (GST) activity and decreased nitrite plus nitrate (NOx)
and malondialdehyde (MDA) concentrations on day 3 and 5 compared to supportive
treatment in parvo-infected dogs. However, supportive treatment alone failed to
ameliorate oxidative stress in the infected dogs till day 5. The results of this
study suggest that NAC represents a potential additional treatment option that
could be considered to improve the health condition and minimize the duration of
hospitalization in case of canine parvoviral diarrhea.
PMID- 28703422
TI - Comparison of two interdental cleaning aids: A randomized clinical trial.
AB - AIM: The aim of this study was a comparison of the handling and acceptance of two
kinds of interdental brushes (interdental brush with a handle [HB] and a newly
invented interdental cleaning device [NB]). METHODS AND MATERIALS: In a
randomized crossover trial, 40 test subjects with an average number of 23.5
interdental areas were examined. At two appointments with a "washout" period of
one week, the volunteers tried out both cleaning tools (HB and NB). They were
asked to clean as many interdental spaces as possible. The percentage of spaces,
which could be reached, is the IRI (Interdental Reachability Index). Furthermore,
subjective impressions were determined. RESULTS: The average IRI using HB was 64%
compared to 80% using of NB (P<.001); 62.5% of the volunteers found the cleaning
with HB painful and 15% the cleaning with NB. The subjective feeling after
cleaning was 1.75 with NB compared to 2.2 with HB (P=.015), grading the feeling,
from 1 for "very good" to 5 for "poor." The acceptance of regular interdental
hygiene was rated 1.95 in the case of the NB and 2.85 in the case of the HB.
After both appointments, the test subjects declared that they would use the NB
3.05 times and the HB 1.78 times a week. CONCLUSION: This study shows that the
test subjects reached more interdental spaces with NB than with the HB. NB can
improve the usage of interdental brushes. Regarding subjective comfort,
participants also favoured NB over HB.
PMID- 28703424
TI - TiO2 -coated fluoride nanoparticles for dental multimodal optical imaging.
AB - Core-shell nanostructures associated with photonics techniques have found
innumerous applications in diagnostics and therapy. In this work, we introduce a
novel core-shell nanostructure design that serves as a multimodal optical imaging
contrast agent for dental adhesion evaluation. This nanostructure consists of a
rare-earth-doped (NaYF4 :Yb 60%, Tm 0.5%)/NaYF4 particle as the core (hexagonal
prism, ~51 nm base side length) and the highly refractive TiO2 material as the
shell (~thickness of 15 nm). We show that the TiO2 shell provides enhanced
contrast for optical coherence tomography (OCT), while the rare-earth-doped core
upconverts excitation light from 975 nm to an emission peaked at 800 nm for
photoluminescence imaging. The OCT and the photoluminescence wide-field images of
human tooth were demonstrated with this nanoparticle core-shell contrast agent.
In addition, the described core-shell nanoparticles (CSNps) were dispersed in the
primer of a commercially available dental bonding system, allowing clear
identification of dental adhesive layers with OCT. We evaluated that the presence
of the CSNp in the adhesive induced an enhancement of 67% scattering coefficient
to significantly increase the OCT contrast. Moreover, our results highlight that
the upconversion photoluminescence in the near-infrared spectrum region is
suitable for image of deep dental tissue.
PMID- 28703425
TI - Optimism, pessimism, cynical hostility, and biomarkers of metabolic function in
the Women's Health Initiative.
AB - BACKGROUND: Psychological attitudes reflecting expectations about the future
(optimism, pessimism) and people (cynical hostility) independently predict
incident cardiovascular disease and possibly diabetes, but underlying biologic
pathways are incompletely understood. Herein we examined the cross-sectional
relationship between optimism, pessimism, and cynicism and biomarkers of
metabolic function in the Women's Health Initiative. METHODS: Among 3443
postmenopausal women, biomarkers of metabolic function (fasting insulin [FINS]
and glucose) were measured at baseline and used to calculate insulin resistance
(homeostasis model assessment of insulin resistance [HOMA-IR]) and pancreatic
beta-cell activity (homeostasis model assessment of beta-cell function [HOMA-B]).
Psychological attitudes were assessed by the Life Orientation Test, Revised (full
scale, and optimism and pessimism subscales) and the Cook-Medley cynicism
subscale. Multivariable linear regression modeled the association of
psychological attitudes with biomarker levels, adjusting for sociodemographics,
health conditions, and health behaviors. Because obesity promotes insulin
resistance and obese individuals tend to report higher levels of pessimism and
cynical hostility, an interaction with body mass index (BMI) was explored.
RESULTS: In fully adjusted models, only pessimism remained independently
associated with higher FINS and insulin resistance (HOMA-IR). Scoring 1 point
higher on the pessimism subscale was associated with a 1.2% higher FINS, whereas
scoring 1 SD higher was associated with a 2.7% higher FINS (P = 0.03); results
were similar for HOMA-IR. An interaction term with BMI was not significant.
CONCLUSIONS: In multivariable models, higher dispositional pessimism was
associated with worse metabolic function; these findings were not modified by
obesity status. Results extend prior work by linking pessimism to an objective
biomarker of insulin resistance in elderly women.
PMID- 28703426
TI - Employment after heart transplantation among adults with congenital heart
disease.
AB - OBJECTIVE: Adults with congenital heart disease may require heart transplantation
for end-stage heart failure. Whereas heart transplantation potentially allows
adults with congenital heart disease to resume their usual activities, employment
outcomes in this population are unknown. Therefore, we investigated the
prevalence and predictors of work participation after heart transplantation for
congenital heart disease. DESIGN: Retrospective review of a prospective registry.
SETTING: United Network for Organ Sharing registry of transplant recipients in
the United States. PATIENTS: Adult recipients of first-time heart transplantation
with a primary diagnosis of congenital heart disease, performed between 2004 and
2015. INTERVENTIONS: None. OUTCOME MEASURES: Employment status reported by
transplant centers at required follow-up intervals up to 5 y posttransplant.
RESULTS: Among 470 patients included in the analysis (mean follow-up: 5 +/- 3 y),
127 (27%) worked after transplant, 69 (15%) died before beginning or returning to
work, and 274 (58%) survived until censoring, but did not participate in paid
work. Multivariable competing-risks regression analysis examined characteristics
associated with posttransplant employment, accounting for mortality as a
competing outcome. In descriptive and multivariable analysis, pretransplant work
participation was associated with a greater likelihood of posttransplant
employment, while the use of Medicaid insurance at the time of transplant was
associated with a significantly lower likelihood of working after transplant
(subhazard ratio compared to private insurance: 0.55; 95% confidence interval:
0.32, 0.95; P = .032). CONCLUSIONS: Employment was rare after heart
transplantation for congenital heart disease, and was significantly less common
than in the broader population of adults with congenital heart disease.
Differences in return to work were primarily related to pretransplant employment
and the use of public insurance, rather than clinical characteristics.
PMID- 28703423
TI - The emerging role of alternative splicing in senescence and aging.
AB - Deregulation of precursor mRNA splicing is associated with many illnesses and has
been linked to age-related chronic diseases. Here we review recent progress
documenting how defects in the machinery that performs intron removal and
controls splice site selection contribute to cellular senescence and organismal
aging. We discuss the functional association linking p53, IGF-1, SIRT1, and ING-1
splice variants with senescence and aging, and review a selection of splicing
defects occurring in accelerated aging (progeria), vascular aging, and
Alzheimer's disease. Overall, it is becoming increasingly clear that changes in
the activity of splicing factors and in the production of key splice variants can
impact cellular senescence and the aging phenotype.
PMID- 28703427
TI - Light-based devices in the treatment of cutaneous vascular lesions: An updated
review.
AB - BACKGROUND: Light-based devices have been used to treat cutaneous vascular
lesions almost since the original development of the laser. After the
introduction of the initial continuous wave and pulsed laser systems, the pulsed
lasers became the gold standard device. Since then, new devices and methods to
treat patients have been introduced. OBJECTIVE: To review and summarize the
current literature specific to treatment of cutaneous vascular lesions with light
based devices. METHODS: A review of the current literature of light-based devices
used for the treatment of vascular lesions. RESULTS AND CONCLUSIONS: New systems
continue to be developed to treat vascular lesions with advantages and
disadvantages compared to older devices. Nonlaser sources such as intense pulsed
light and radiofrequency devices can also be used in the treatment of these
patients. Newer approaches may lead to even better results.
PMID- 28703430
TI - Sharp nonparametric bounds and randomization inference for treatment effects on
an ordinal outcome.
AB - In clinical research, investigators are interested in inferring the average
causal effect of a treatment. However, the causal parameter that can be used to
derive the average causal effect is not well defined for ordinal outcomes.
Although some definitions have been proposed, they are limited in that they are
not identical to the well-defined causal risk for a binary outcome, which is the
simplest ordinal outcome. In this paper, we propose the use of a causal parameter
for an ordinal outcome, defined as the proportion that a potential outcome under
one treatment condition would not be smaller than that under the other condition.
For a binary outcome, this proportion is identical to the causal risk.
Unfortunately, the proposed causal parameter cannot be identified, even under
randomization. Therefore, we present a numerical method to calculate the sharp
nonparametric bounds within a sample, reflecting the impact of confounding. When
the assumption of independent potential outcomes is included, the causal
parameter can be identified when randomization is in play. Then, we present exact
tests and the associated confidence intervals for the relative treatment effect
using the randomization-based approach, which are an extension of the existing
methods for a binary outcome. Our methodologies are illustrated using data from
an emetic prevention clinical trial.
PMID- 28703431
TI - A matter of hierarchy: activation of orfamide production by the post
transcriptional Gac-Rsm cascade of Pseudomonas protegens CHA0 through expression
upregulation of the two dedicated transcriptional regulators.
AB - In this work, we surveyed the genome of P. protegens CHA0 in order to identify
novel mRNAs possibly under the control of the Gac-Rsm cascade that might, for
their part, serve to elucidate as-yet-unknown functions involved in the
biocontrol of plant pathogens and/or in cellular processes required for fitness
in natural environments. In view of the experimental evidence from former studies
on the Gac-Rsm cascade, we developed a computational screen supported by a
combination of sequence, structural and evolutionary constraints that led to a
dataset of 43 potential novel mRNA targets. We then confirmed several mRNA
targets experimentally and next focused on two of the respective genes that are
physically linked to the orfamide biosynthetic gene cluster and whose predicted
open-reading frames resembled cognate LuxR-type transcriptional regulators of
cyclic lipopeptide clusters in related pseudomonads. In this report, we
demonstrate that in strain CHA0, orfamide production is stringently dependent on
a functional Gac-Rsm cascade and that both mRNAs encoding transcriptional
regulatory proteins are under direct translational control of the RsmA/E
proteins. Our results have thus revealed a hierarchical control over the
expression of orfamide biosynthetic genes with the final transcriptional control
subordinated to the global Gac-Rsm post-transcriptional regulatory system.
PMID- 28703432
TI - The mutual effect of a carbonyl polar bond and an endocyclic oxygen on the 1 JC-F
coupling constant of fluorinated six-membered rings.
AB - The 1 JC-F coupling constant can be useful to probe the conformational landscape
of organofluorine compounds and the intramolecular interactions governing the
stereochemistry of these compounds. Neighboring oxygen electron lone pairs and a
carbonyl group relative to a C?F bond affect this coupling constant in an
opposite way, and therefore, analysis of the interactions involving these
entities simultaneously indicates which effect dominates 1 JC-F . Spin-spin
coupling constant calculations for a series of fluorinated tetrahydropyrans,
cyclohexanones, and dihydropyran-3-ones indicated that an electrostatic/dipolar
interaction between the C?F and C?O bonds is more important than the steric
interaction between the C?F bond and the oxygen electron lone pairs. An intuitive
consequence of such outcome is that this interaction not only drives the coupling
constant but can also be taken into account when aiming at the stereochemical
control of functionalized organofluorine compounds.
PMID- 28703433
TI - Accessing Low-Valent Inorganic Cations by Using an Extremely Bulky N-Heterocyclic
Carbene.
AB - The extremely bulky N-heterocyclic carbene (NHC), ITr (ITr=[(HCNCPh3 )2 C:])
featuring sterically shielding umbrella-shaped trityl (CPh3 ) substituents was
prepared. This NHC features the highest percent buried volume (%Vbur ) to date,
and was used to form a thermally stable quasi one-coordinate thallium(I) cation
[ITr-Tl]+ . This TlI adduct and the corresponding lithium complex [ITr?Li(OEt2
)]+ are versatile "all-in-one" transmetalation/ligation reagents for preparing
low-coordinate inorganic species inaccessible by pre-existing routes.
PMID- 28703434
TI - Porphyromonas gingivalis lipopolysaccharides affect gingival stem/progenitor
cells attributes through NF-kappaB, but not Wnt/beta-catenin, pathway.
AB - AIM: This study investigates for the first time the effect of Porphyromonas
gingivalis lipopolysaccharides (Pg-LPS) on proliferative/regenerative aptitudes
of gingival stem/progenitor cells (G-MSCs). MATERIAL AND METHODS: G-MSCs (n = 5)
were treated by 0, 10 ng/ml, 100 ng/ml, 1 MUg/ml or 10 MUg/ml Pg-LPS. At 1 hour,
Toll-like receptor 4 (TLR-4) expression and NF-kappaB and Wnt/beta-catenin
signalling pathways were examined. Colony-forming unit assay was conducted at day
12. At 24 and 48 hours, MTT test, ALP activity, mRNA for tumour necrosis factor
alpha (TNF-alpha), interleukin-6, collagen-I (Col-I), collagen-III, RUNX-2,
alkaline phosphatase (ALP), osteonectin and protein expression of interleukin-6
and TNF-alpha were analysed. RESULTS: With increasing Pg-LPS, TLR-4 was
upregulated, pNF-kappaB-p65 rose from median (Q25/Q75) 6.56% (4.19/7.90) to
13.02% (8.90/16.50; p = 0.002) and pNF-kappaB-p65/tNF-kappaB-p65 from
0.14(0.10/0.17) to 0.30(0.21/0.42; p = 0.002). pbeta-Catenin, tbeta-catenin and
pbeta-catenin/tbeta-catenin showed no differences. Increasing Pg-LPS
concentration increased cell numbers from 288.00(72.98/484.32) to 861.39
(540.41/1599.94; p = 0.002), ALP mRNA from 0.00(0.00/0.01) to 0.56(0.00/1.90; p =
0.004) and TNF-alpha from 32.47(12.11/38.57) to 45.32(28.68/48.65; p = 0.036).
Over time, ALP activity increased from 0.89(0.78/0.95) to 1.90(1.83/2.09; p <
0.001), mRNA for TNF-alpha from 0.00(0.00/0.12) to 0.01(0.00/0.06; p = 0.007),
mRNA for Col-I from 82.70(0.03/171.50) to 124.00(52.85/232.50; p = 0.019), while
mRNA for RUNX-2 decreased from 1.73(0.92/3.20) to 0.84(0.48/1.47; p = 0.005).
CONCLUSIONS: Pg-LPS upregulated G-MSCs' proliferation, without attenuation of
their regenerative potential. The effects were NF-kappaB, but not Wnt/beta
catenin, pathway dependent.
PMID- 28703435
TI - Robotic mitral valve plasty for mitral regurgitation after blunt chest trauma in
Barlow's disease.
AB - We successfully treated a case of mitral regurgitation due to chest trauma in
Barlow's disease. A 71-year-old man was admitted with severe mitral regurgitation
after blunt compression of the chest by a heavy object 5 months earlier.
Preoperative examination revealed wide chordae tendineae rupture and myxomatous
changes to the bileaflets. Neo-chordae reconstruction of the anterior mitral
leaflet using loop technique, triangular resection of the posterior mitral
leaflet, and ring annuloplasty was performed via surgical robot. Robotic mitral
valve plasty for severe mitral regurgitation due to chest trauma in Barlow's
disease was achieved safely with good clinical and excellent cosmetic results.
PMID- 28703436
TI - Approach Matters: The Kinetics of Interfacial Inverse-Electron Demand Diels-Alder
Reactions.
AB - Rapid and quantitative click functionalization of surfaces remains an interesting
challenge in surface chemistry. In this regard, inverse electron demand Diels
Alder (IEDDA) reactions represent a promising metal-free candidate. Herein, we
reveal quantitative surface functionalization within 15 min. Furthermore, we
report the comprehensive effects of substrate stereochemistry, surrounding
microenvironment and substrate order on the reaction kinetics as obtained by
surface-bound mass spectrometry (DART-HRMS).
PMID- 28703437
TI - An in vitro study of the interaction of the chemotherapeutic drug Actinomycin D
with lung cancer cell lines using Raman micro-spectroscopy.
AB - The applications of Raman microspectroscopy have been extended in recent years
into the field of clinical medicine, and specifically in cancer research, as a
non-invasive diagnostic method in vivo and ex vivo, and the field of
pharmaceutical development as a label-free predictive technique for new drug
mechanisms of action in vitro. To further illustrate its potential for such
applications, it is important to establish its capability to fingerprint drug
mechanisms of action and different cellular reactions. In this study,
cytotoxicity assays were employed to establish the toxicity profiles for 48 and
72 hours exposure of lung cancer cell lines, A549 and Calu-1, after exposure to
Actinomycin D (ACT) and Raman micro-spectroscopy was used to track its mechanism
of action at subcellular level and subsequent cellular responses. Multivariate
data analysis was used to elucidate the spectroscopic signatures associated with
ACT chemical binding and cellular resistances. Results show that the ACT uptake
and mechanism of action are similar in the 2 cell lines, while A549 cells
exhibits spectral signatures of resistance to apoptosis related to its higher
chemoresistance to the anticancer drug ACT. The observations are discussed in
comparison to previous studies of the similar anthracyclic chemotherapeutic agent
Doxorubicin. A, Preprocessed Raman spectrum of ACT stock solution dissolved in
sterile water and mean spectrum with SD of (B) nucleolus, (C) nucleus and (D)
cytoplasm of A549 cell lines after 48 hours exposure to the corresponding IC50 .
PMID- 28703438
TI - Response to: Can patients with chronic rhinosinusitis recover normal sleep after
endoscopic sinus surgery?
PMID- 28703439
TI - Laparoendoscopic single-site surgery in inguinal hernia repair.
AB - Laparoendoscopic single-site surgery (LESS) for laparoscopic inguinal hernia
repair (IHR) offers the potential for excellent cosmetic outcomes and
maximization of the inherent advantages of minimally invasive surgery. LESS IHR
is associated with a steep learning curve, which is attributable to both the IHR
technique itself and the single-site technique. The technical obstacles in the
single-site technique may be mitigated by employing certain maneuvers and
strategies that minimize clashing between instruments and improve freedom of
movement. The current literature consistently points out the inherent challenges
in LESS IHR, with its longer operative time compared to that of conventional
laparoscopic IHR. LESS IHR performed by capable operators has comparable
complication rates, duration of hospital stay, and incidence of recurrence as
conventional laparoscopic IHR. LESS IHR is both feasible and safe. Given its
excellent cosmetic outcome, it is likely to be sought by younger patients who are
concerned with scar formation. The use of robotics may bypass the technical
challenges in LESS, but cost considerations in their usage will likely persist.
PMID- 28703440
TI - Effect of community-based education to Korean mothers in relation to the
prevention of cervical cancer in their daughters: A non-randomized trial.
AB - AIM: This study was conducted in order to examine the effects of community-based
education on cervical cancer prevention in relation to South Korean mothers'
knowledge about the Papanicolau (Pap) test and human papillomavirus, self
confidence in communication with their daughters, and health-related beliefs
about their daughters. METHODS: A quasi-experimental pre-post design was used.
For the experimental group, face-to-face education was administered to 35
participants for 60 min. For the control group, 35 participants were taught by
using standardized materials for 20 min. RESULTS: The experimental group showed a
significant increase in Pap test knowledge, cervical cancer knowledge, and self
confidence in communication with their daughters, compared to the control group.
In the post-test, the mothers in the experimental group also perceived cervical
cancer as more threatening, their daughter as more susceptible to cervical
cancer, Pap tests as being recommended for their daughters, and they showed a
significant increase in their self-efficacy of recommending the Pap test to their
daughter. CONCLUSION: Community-based education for mothers is effective in
increasing their human papillomavirus knowledge, Pap test knowledge, improving
their confidence in communication with their daughters, and in some of the health
related beliefs regarding their daughters.
PMID- 28703441
TI - Discovery of Small Molecules that Induce the Degradation of Huntingtin.
AB - Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder
caused by the aggregation of mutant huntingtin (mHtt), and removal of toxic mHtt
is expected to be an effective therapeutic approach. We designed two small hybrid
molecules (1 and 2) by linking a ligand for ubiquitin ligase (cellular inhibitor
of apoptosis protein 1; cIAP1) with probes for mHtt aggregates, anticipating that
these compounds would recruit cIAP1 to mHtt and induce selective degradation by
the ubiquitin-proteasome system. The synthesized compounds reduced mHtt levels in
HD patient fibroblasts and appear to be promising candidates for the development
of a treatment for HD.
PMID- 28703442
TI - Measurement of absolute copy number variation of Glutathione S-Transferase M1
gene by digital droplet PCR and association analysis in Tunisian Rheumatoid
Arthritis population.
AB - BACKGROUND: The investigation of copy number variations (CNVs) analysis of
candidate genes is currently an important research area in modulating human
diseases. We aimed to quantify CNVs in glutathione S-transferase M1 (GSTM1) gene
and determine its genetic contribution in Tunisian rheumatoid arthritis (RA) and
its subsets through an innovative technique for quantification. METHODS: A total
of 165 RA cases and 102 healthy controls were included in the study. Using a
recently powerful approach of digital droplet PCR (ddPCR), we quantified GSTM1
gene to determine the presence of no, one, or multiple copy number (CN) at high
levels of sensitivity and specificity. Odds ratio and Fisher exact test were
performed to estimate the association risk for GSTM1CNVs in RA. RESULTS: Copy
number identified by ddPCR was 0, 1, and 2 copies per diploid genome. A high
frequency of '0' copy was revealed with 54% in RA patients. The deletion ('0'
copy) of GSTM1 was found to be a significant risk factor for anti-cyclic
citrullinated peptide (anti-CCP) positive RA (OR=4.16, CI95% =[1.17-14.7]). In
addition, a lack of association was found when comparing between the CNVs of RA
patients and those of controls. CONCLUSION: This study highlights the powerful
accuracy of ddPCR for the quantification of CNVs and suggests that the variation
in the CN of GSTM1 is associated with anti-CCP positivity in RA. However, it does
not indicate a specific role in the susceptibility to the disease in our Tunisian
sample.
PMID- 28703443
TI - Patient satisfaction with a rapid diagnosis of suspicious breast lesions:
Association with distress and anxiety.
AB - Few studies have explored with standard measures patient satisfaction with care
at the time of the diagnosis through rapid diagnostic pathways. This study aimed
to assess satisfaction levels at the time of the diagnosis in a One-Stop Breast
Unit and to examine associations with psychological states. An anonymous cross
sectional survey was conducted at a single center's One-Stop Breast Unit, to
assess patient satisfaction regarding several aspects of the Unit. Two days after
the diagnosis, 113 participants completed self-reported questionnaires evaluating
satisfaction (Out-Patsat35), anxiety (State Anxiety Inventory), and psychological
distress (Distress Thermometer). Overall, patients were very satisfied (80.7+/
20.7) with the One-Stop Breast Unit. The highest mean satisfaction scores
concerned nurses' technical skills, interpersonal skills and availability. The
lowest mean scores concerned physicians' availability, waiting time, and the
provision of information. The results revealed a significant association between
high state anxiety levels, lower levels of satisfaction with doctors'
interpersonal skills (r=-.41, P<.001) and lower levels for information provided
by nurses (r=-.38, P<.001). Moreover, greater psychological distress was
associated with less satisfaction with the different aspects of care (doctors'
interpersonal skills, doctors' availability and waiting-time). The results of
regression models showed that doctor-related satisfaction scales explained 20% of
the variance in anxiety (P<.01). Facing cancer diagnosis remains a stressful
situation. However, our study suggested that a substantial part of this anxiety
is sensitive to the quality of the patient-doctor relationship. Consequently,
further efforts should be expended on adapting patient-doctor communication to
improve patient reassurance.
PMID- 28703445
TI - Erratum.
PMID- 28703444
TI - Comparison of acute toxicities between contemporary forward-planned 3D conformal
radiotherapy and inverse-planned intensity-modulated radiotherapy for whole
breast radiation.
AB - The use of inverse-planned intensity-modulated radiation therapy for whole breast
radiation treatment has become more prevalent, but this may impose an increased
cost on the health system. We hypothesized that when applied with the same
treatment planning goals, tangential forward-planned field-in-field 3D conformal
radiotherapy and tangential inverse-planned intensity-modulated radiotherapy
would be associated with comparable toxicities. Women who underwent tangential
whole breast irradiation at our institution from 2011 to 2015 planned using
either forward-planned field-in-field 3D conformal radiotherapy or intensity
modulated radiotherapy were retrospectively analyzed. Grade 2+ Radiation
dermatitis was the primary endpoint. A total of 201 and 212 women had undergone
field-in-field 3D conformal radiotherapy and intensity-modulated radiotherapy,
respectively. No differences were observed between the two modalities regarding
acute radiation dermatitis, breast pain, or fatigue. In a multivariable logistic
regression that incorporated the use of boost, hypofractionation, use of
chemotherapy, patient positioning, use of a supraclavicular field, and breast
planning target volume, intensity-modulated radiotherapy was not correlated with
different rates of Grade 2+ radiation dermatitis. This study supports the routine
first-line use of field-in-field 3D conformal radiotherapy for whole breast
radiation instead of tangential intensity-modulated radiotherapy from the
standpoint of equivalence in acute toxicity. Further investigation is needed to
assess whether there are subgroups of women who may still benefit from intensity
modulated radiotherapy.
PMID- 28703446
TI - Paroxysmal Dyskinesia in Border Terriers: Clinical, Epidemiological, and Genetic
Investigations.
AB - BACKGROUND: In the last decade, a disorder characterized by episodes of
involuntary movements and dystonia has been recognized in Border Terriers.
OBJECTIVES: To define clinical features of paroxysmal dyskinesia (PD) in a large
number of Border Terriers and to study the genetics of the disease. ANIMALS: 110
affected and 128 unaffected client-owned Border Terriers. METHODS: A
questionnaire regarding clinical characteristics of PD was designed at Utrecht
University and the University of Helsinki. Thirty-five affected Border Terriers
underwent physical examination and blood testing (hematology and clinical
biochemistry). Diagnostic imaging of the brain was performed in 17 affected dogs
and electroencephalograms (EEG) between episodes were obtained in 10 affected
dogs. A genomewide association study (GWAS) was performed with DNA of 110
affected and 128 unaffected dogs. RESULTS: One hundred forty-seven questionnaires
were included in the study. The most characteristic signs during episodes were
dystonia, muscle fasciculations, and falling over. The majority of owners
believed that their dogs remained conscious during the episodes. A beneficial
effect of anti-epileptic therapy was observed in 29 of 43 dogs. Fifteen owners
changed their dogs' diet to a hypoallergenic, gluten-free diet, and all reported
reasonable to good improvement of signs. Clinical examinations and diagnostic
test results were unremarkable. The GWAS did not identify significantly
associated chromosome regions. CONCLUSIONS AND CLINICAL IMPORTANCE: The survey
results and EEG studies provided further evidence that the observed syndrome is a
PD rather than epilepsy. Failure to achieve conclusive results by GWAS indicates
that inheritance of PD in Border Terriers probably is complex.
PMID- 28703447
TI - Chronic Diarrhea in Dogs - Retrospective Study in 136 Cases.
AB - BACKGROUND: Chronic diarrhea (CD) is common in dogs, and information on frequency
and distribution of primary and secondary causes is lacking. OBJECTIVES: To
evaluate underlying causes and predictors of outcome in dogs with CD. ANIMALS:
One hundred and thirty-six client-owned dogs with CD (>=3 weeks duration).
METHODS: Retrospective review of medical records (Small Animal Clinic, Freie
Universitat Berlin, Germany, 09/2009-07/2011). Quantification of final diagnoses
and comparison of clinical aspects including disease severity and
clinicopathological abnormalities among dogs with clinical remission (either
complete [gastrointestinal signs absent] or partial [clinical improvement of
gastrointestinal signs and reduced episodes with shortened duration]), and those
without recovery. RESULTS: Ninety percent of dogs were diagnosed with a primary
enteropathy: inflammatory (71%; of those 66% dietary responsive, 23% idiopathic,
11% antibiotic responsive), infectious (13%), neoplastic (4%), and in one dog
each mechanical disease or systemic vasculitis. Secondary causes were diagnosed
in 10% of dogs: exocrine pancreatic (6%), endocrine (2%), and in one dog each
hepatic, renal, and cardiac disease. In total, 87% of dogs had clinical
remission, whereas 13% died or did not respond to treatment: Lack of recovery was
frequently recorded for dogs with primary inflammatory (idiopathic) or neoplastic
disease and was significantly associated with increased disease severity scores
(P = .005), anemia (hematocrit < 40%, P < .001), severe hypoalbuminemia (serum
albumin <2.0 g/dL, P = .008), and severe hypocobalaminemia (serum cobalamin
concentration <200 pg/mL, P = .006). CONCLUSIONS AND CLINICAL IMPORTANCE:
Inflammatory enteropathies and particularly those of dietary origin were the most
common causes of CD in dogs. Findings support the usefulness of hematocrit, and
serum albumin and cobalamin concentration as prognostic markers in dogs with CD.
PMID- 28703448
TI - The Effect of Different Types of Monitoring Strategies on Weight Loss: A
Randomized Controlled Trial.
AB - OBJECTIVE: To determine the effectiveness of various monitoring strategies on
weight loss, body composition, blood markers, exercise, and psychosocial indices
in adults with overweight and obesity following a 12-month weight loss program.
METHODS: Two hundred fifty adults with BMI >= 27 were randomized to brief,
monthly, individual consults, daily self-monitoring of weight, self-monitoring of
diet using MyFitnessPal, self-monitoring of hunger, or control over 12 months.
All groups received diet and exercise advice, and 171 participants (68.4%)
remained at 12 months. RESULTS: No significant differences in weight, body
composition, blood markers, exercise, or eating behavior were apparent between
those in the four monitoring groups and the control condition at 12 months (all P
>= 0.053). Weight differences between groups ranged from -1.1 kg (-3.8 to 1.6) to
2.2 kg (-1.0 to 5.3). However, brief support and hunger training groups reported
significantly lower scores for depression (difference [95% CI]: -3.16 [-5.70 to
0.62] and -3.05 [-5.61 to -0.50], respectively) and anxiety (-1.84, [-3.67 to
0.02]) scores than control participants. CONCLUSIONS: Although adding a
monitoring strategy to diet and exercise advice did not further increase weight
loss, no adverse effects on eating behavior were observed, and some monitoring
strategies may even benefit mental health.
PMID- 28703449
TI - Sero-prevalence and epidemiology of peste des petits ruminants in Libya.
AB - We conducted a cross-sectional study during 2013 to quantify the serological
prevalence of peste des petits ruminants (PPR) infection and to investigate host
factors associated with PPR infection in small ruminants in Libya. A two-stage
sampling design was carried out. A total number of 148 flocks owning at least 100
heads each were randomly selected. Sixteen to forty-eight samples were collected
from each selected flock. A total number of 3,508 serum samples from unvaccinated
animals were collected and analysed at IZSLER Brescia, Italy, by using
competitive ELISA, IDvet innovative diagnostics (IDvet 310, France). The overall
serological prevalence among SR was 33% (95% CI: 31.4-34.5). Significant
differences between the prevalence in the geographical branches were observed.
The lowest prevalence level was observed in Zawiyah branch (16.1%), whereas the
highest value was obtained for the Sabha branch (56.8%). Considering the age, a
serological prevalence of 24.7%, 31.5% and 42.1% was observed in SR <1 year,
between 1 and 2 years and more than 2 years, respectively. Statistically
significant differences (p < .001) in the sero-prevalence levels were also
observed between the age groups. Our findings suggest that the southern part of
Libya could be more exposed to the infections coming from the neighbouring
countries and this should be better investigated to correctly identify wherever
specific entry points can be considered at higher risk than others. The results
also confirmed the endemic status of PPR in Libya, with a constant exposure to
the infection of the animals during their life. In the framework of the global
strategy for control and eradication of PPR, our results, even if obtained by a
preliminary study, can contribute to the assessment of the epidemiological
situation of PPR in Libya as required by the Stage 1 of the plan.
PMID- 28703450
TI - Comparative transcriptome combined with morpho-physiological analyses revealed
key factors for differential cadmium accumulation in two contrasting sweet
sorghum genotypes.
AB - Cadmium (Cd) is a widespread soil contaminant threatening human health. As an
ideal energy plant, sweet sorghum (Sorghum bicolor (L.) Moench) has great
potential in phytoremediation of Cd-polluted soils, although the molecular
mechanisms are largely unknown. In this study, key factors responsible for
differential Cd accumulation between two contrasting sweet sorghum genotypes
(high-Cd accumulation one H18, and low-Cd accumulation one L69) were
investigated. H18 exhibited a much higher ability of Cd uptake and translocation
than L69. Furthermore, Cd uptake through symplasmic pathway and Cd concentrations
in xylem sap were both higher in H18 than those in L69. Root anatomy observation
found the endodermal apoplasmic barriers were much stronger in L69, which may
restrict the Cd loading into xylem. The molecular mechanisms underlying these
morpho-physiological traits were further dissected by comparative transcriptome
analysis. Many genes involved in cell wall modification and heavy metal transport
were found to be Cd-responsive DEGs and/or DEGs between these two genotypes. KEGG
pathway analysis found phenylpropanoid biosynthesis pathway was over-represented,
indicating this pathway may play important roles in differential Cd accumulation
between two genotypes. Based on these results, a schematic representation of main
processes involved in differential Cd uptake and translocation in H18 and L69 is
proposed, which suggests that higher Cd accumulation in H18 depends on a
multilevel coordination of efficient Cd uptake and transport, including efficient
root uptake and xylem loading, less root cell wall binding, and weaker endodermal
apoplasmic barriers.
PMID- 28703451
TI - A novel and independent method for time-resolved gantry angle quality assurance
for VMAT.
AB - Volumetric-modulated arc therapy (VMAT) treatment delivery requires three key
dynamic components; gantry rotation, dose rate modulation, and multi-leaf
collimator motion, which are all simultaneously varied during the delivery.
Misalignment of the gantry angle can potentially affect clinical outcome due to
the steep dose gradients and complex MLC shapes involved. It is essential to
develop independent gantry angle quality assurance (QA) appropriate to VMAT that
can be performed simultaneously with other key VMAT QA testing. In this work, a
simple and inexpensive fully independent gantry angle measurement methodology was
developed that allows quantitation of the gantry angle accuracy as a function of
time. This method is based on the analysis of video footage of a "Double dot"
pattern attached to the front cover of the linear accelerator that consists of
red and green circles printed on A4 paper sheet. A standard mobile phone is
placed on the couch to record the video footage during gantry rotation. The video
file is subsequently analyzed and used to determine the gantry angle from each
video frame using the relative position of the two dots. There were two types of
validation tests performed including the static mode with manual gantry angle
rotation and dynamic mode with three complex test plans. The accuracy was 0.26
degrees +/- 0.04 degrees and 0.46 degrees +/- 0.31 degrees (mean +/- 1 SD)
for the static and dynamic modes, respectively. This method is user friendly,
cost effective, easy to setup, has high temporal resolution, and can be combined
with existing time-resolved method for QA of MLC and dose rate to form a
comprehensive set of procedures for time-resolved QA of VMAT delivery system.
PMID- 28703452
TI - Cover Image, Volume 173A, Number 8, August 2017.
AB - The cover image, by Monica H. Wojcik et al., is based on the Clinical Report A
new diagnosis of Williams-Beuren syndrome in a 49-year-old man with severe
bullous emphysema, DOI: 10.1002/ajmg.a.38289.
PMID- 28703453
TI - Greater focus on patient data sharing urged: Greater control of data may increase
patients' sharing and empowerment.
PMID- 28703454
TI - 23andMe resumes giving consumers genetic health information: Company's tests for
rare and common diseases aren't diagnostic.
PMID- 28703456
TI - Two-Dimensional Seeded Self-Assembly of a Complex Hierarchical Perylene-Based
Heterostructure.
AB - A complex two-dimensional (2D) hierarchical heterostructure was fabricated by a
sequential two-dimensional seeded self-assembly, which consisted of laterally
grown nanotubes from one perylene monomer and terminally elongated nanocoils from
a similar perylene monomer on microribbon seeds from a third perylene. Because
the nanotube and nanocoil monomers can form kinetically trapped off-pathway
aggregates to prevent self-nucleation and have similar molecular organizations to
different facets of the seeds, the nanotube and nanocoil monomers preferentially
nucleate and grow on the seed sides and terminal ends, respectively, to form a
complex 2D hierarchical heterostructure. The strategy used in this work can be
extended to fabricate other complex nanoarchitectures from small molecules.
PMID- 28703457
TI - Fluorescent Probes with Multiple Binding Sites for the Discrimination of Cys,
Hcy, and GSH.
AB - Biothiols such as cysteine (Cys), homocysteine (Hcy), and glutathione (GSH) play
crucial roles in maintaining redox homeostasis in biological systems. This
Minireview summarizes the most significant current challenges in the field of
thiol-reactive probes for biomedical research and diagnostics, emphasizing the
needs and opportunities that have been under-investigated by chemists in the
selective probe and sensor field. Progress on multiple binding site probes to
distinguish Cys, Hcy, and GSH is highlighted as a creative new direction in the
field that can enable simultaneous, accurate ratiometric monitoring. New probe
design strategies and researcher priorities can better help address current
challenges, including the monitoring of disease states such as autism and chronic
diseases involving oxidative stress that are characterized by divergent levels of
GSH, Cys, and Hcy.
PMID- 28703458
TI - Hybrid Deep Eutectic Solvents with Flexible Hydrogen-Bonded Supramolecular
Networks for Highly Efficient Uptake of NH3.
AB - Serious environmental concerns have led to a great demand for efficient uptake of
NH3 by solvents. However, traditional aqueous absorbents have many shortcomings
and efforts to use ionic liquids have met with limited success. A hybrid deep
eutectic solvents (DESs) designed with a flexible hydrogen-bonded supramolecular
network exhibits both exceptional NH3 uptake capacity and superior desorption
regeneration performance, along with superb NH3 /CO2 selectivity and
environmental merit. Elucidated by molecular dynamic simulations and
spectroscopic analysis, the abundant hydrogen-bonding sites in the hybrid DESs
bind every atom of the NH3 molecule and enable strong physical reversible
solvation, whereas the multiple interactions among the hybrid components create a
flexible hydrogen-bonded supramolecular network and allow for solvent-unbreaking
absorption to ensure the full participation of the solvent and process stability.
A mass solubility of NH3 up to 0.13 g g-1 was achieved at 313 K and 101 kPa by
the hybrid DES choline chloride/resorcinol/glycerol (1:3:5), which is higher than
all reported ionic liquids and ordinary DESs. Moreover, the performance remained
the same after ten absorption-desorption cycles and the DESs could be easily
regenerated.
PMID- 28703459
TI - Efficient Long-Range Hole Transport Through G-Quadruplexes.
AB - DNA offers a means of long-range charge transport for biology and electric
nanodevices. Here, a series of tetra-stranded G-quadruplexes were assembled
within a dendritic DNA architecture to explore oxidative charge transport (hole
transport) through the G-quadruplex. Efficient charge transport was achieved over
28 A upon UV irradiation. Over a longer G-quadruplex bridge, hole transport was
escalated to a higher efficiency, which resulted in a higher yield than that of
the optimal duplex DNA for charge transport, that is, the adenine tract.
Efficient long-range hole transport suggests tetra-stranded G-quadruplexes,
instead of an oxidation hotspot, hold better potential as an electron conduit
than duplex DNA.
PMID- 28703460
TI - Screening for Ptaquiloside in Ferns: Using Herbarium Specimens for Qualitative
Mapping Purposes.
AB - INTRODUCTION: Ptaquiloside (PTA) is a noxious carcinogen found widespread in
Bracken (Pteridium sp.) but with scattered and unresolved distribution outside
the genus. The carcinogen causes Bovine Enzootic Haematuria among cattle all-over
the World and is under suspicion of causing human cancers. OBJECTIVE: To set-up a
methodology for large-scale qualitative studies on the distribution of PTA in
ferns using already available herbarium specimens as source. METHODOLOGY: PTA and
the main degradation product pterosin B (PtB) were quantified in aqueous frond
extracts by HPLC-DAD. PTA was quantified after forced reaction into PtB. Optimal
reaction conditions were tested using hydrochloric acid, sulphuric acid,
trifluoroacetic acid (TFA), acetic acid and temperature as the experimental
variables. A pair-wise test for PTA degradation in plant-press were used to
explore the effect of this preservation regime. A selection of up to 50 years old
Bracken herbarium specimens were tested for PTA and PtB. The methodology was
applied on 21 fern species from Denmark. RESULTS: An optimised TFA-based method
results in 30.7% higher conversion and a 1:1 reaction between PTA and PtB. Full
three-dimensional resolution of the analyte was obtained. Preservation of fronds
in a plant press increase formation of PtB. Hence, the method is only suitable
for qualitative studies. Presence of PTA and PtB were found in samples up to 50
years old. Among 21 ferns tested, the compounds were only found in Pteridium
aquilinum. CONCLUSION: Herbarium specimens up to 50 years old can be used for
explorative risk assessment of ferns using HPLC-DAD for quantification and
identification. Copyright (c) 2017 John Wiley & Sons, Ltd.
PMID- 28703461
TI - Strengthening health systems to provide rehabilitation services.
PMID- 28703462
TI - An emerging model organism Caenorhabditis elegans for alternative pre-mRNA
processing in vivo.
AB - A nematode Caenorhabditis elegans is an intron-rich organism and up to 25% of its
pre-mRNAs are estimated to be alternatively processed. Its compact genomic
organization enables construction of fluorescence splicing reporters with intact
genomic sequences and visualization of alternative processing patterns of
interest in the transparent living animals with single-cell resolution. Genetic
analysis with the reporter worms facilitated identification of trans-acting
factors and cis-acting elements, which are highly conserved in mammals. Analysis
of unspliced and partially spliced pre-mRNAs in vivo raised models for
alternative splicing regulation relying on specific order of intron excision. RNA
seq analysis of splicing factor mutants and CLIP-seq analysis of the factors
allow global search for target genes in the whole animal. An mRNA surveillance
system is not essential for its viability or fertility, allowing analysis of
unproductively spliced noncoding mRNAs. These features offer C. elegans as an
ideal model organism for elucidating alternative pre-mRNA processing mechanisms
in vivo. Examples of isoform-specific functions of alternatively processed genes
are summarized. WIREs RNA 2017, 8:e1428. doi: 10.1002/wrna.1428 For further
resources related to this article, please visit the WIREs website.
PMID- 28703463
TI - Complexation Between (O-Methyl)6 -2,6-Helic[6]arene and Tertiary Ammonium Salts:
Acid/Base- or Chloride-Ion-Responsive Host-Guest Systems and Synthesis of
[2]Rotaxane.
AB - Complexation between (O-methyl)6 -2,6-helic[6]arene and a series of tertiary
ammonium salts was described. It was found that the macrocycle could form stable
complexes with the tested aromatic and aliphatic tertiary ammonium salts, which
were evidenced by 1 H NMR spectra, ESI mass spectra, and DFT calculations. In
particular, the binding and release process of the guests in the complexes could
be efficiently controlled by acid/base or chloride ions, which represents the
first acid/base- and chloride-ion-responsive host-guest systems based on
macrocyclic arenes and protonated tertiary ammonium salts. Moreover, the first
2,6-helic[6]arene-based [2]rotaxane was also synthesized from the condensation
between the host-guest complex and isocyanate.
PMID- 28703465
TI - Structured illumination microscopy with interleaved reconstruction (SIMILR).
AB - Structured illumination microscopy (SIM) is the commonly used super-resolution
(SR) technique for imaging subcellular dynamics. However, due to its need for
multiple illumination patterns, the frame rate is just a fraction of that of
conventional microscopy and is thus too slow for fast dynamic studies. A new SR
image reconstruction method that maximizes the use of each subframe of the
acquisition series is proposed for improving the super-resolved frame rate by N
times for N illumination directions. The method requires no changes in raw data
and is appropriate for many versions of SIM setup, including those implementing
fast illumination pattern generation mechanism based on spatial light modulator
or digital micromirror device. The performance of the proposed method is
demonstrated through imaging the highly dynamic endoplasmic reticulum where
continuous rapid growths or shape changes of tiny structures are observed.
PMID- 28703464
TI - Iron-related markers are associated with infection after liver transplantation.
AB - Though serum iron has been known to be associated with an increased risk of
infection, hepcidin, the major regulator of iron metabolism, has never been
systematically explored in this setting. Finding early biomarkers of infection,
such as hepcidin, could help identify patients in whom early empiric
antimicrobial therapy would be beneficial. We prospectively enrolled consecutive
patients (n = 128) undergoing first-time, single-organ orthotopic liver
transplantation (OLT) without known iron overload disorders at 2 academic
hospitals in Boston from August 2009 to November 2012. Cox regression compared
the associations between different iron markers and the development of first
infection at least 1 week after OLT; 47 (37%) patients developed a primary
outcome of infection at least 1 week after OLT and 1 patient died. After
adjusting for perioperative bleeding complications, number of hospital days, and
hepatic artery thrombosis, changes in iron markers were associated with the
development of infection post-OLT including increasing ferritin (hazard ratio
[HR], 1.51; 95% confidence interval [CI], 1.12-2.05), rising ferritin slope (HR,
1.10; 95% CI, 1.03-1.17), and increasing hepcidin (HR, 1.43; 95% CI, 1.05-1.93).
A decreasing iron (HR, 1.76; 95% CI, 1.20-2.57) and a decreasing iron slope (HR,
4.21; 95% CI, 2.51-7.06) were also associated with subsequent infections. In
conclusion, hepcidin and other serum iron markers and their slope patterns or
their combination are associated with infection in vulnerable patient
populations. Liver Transplantation 23 1541-1552 2017 AASLD.
PMID- 28703466
TI - Functional regulation of Q by microRNA172 and transcriptional co-repressor
TOPLESS in controlling bread wheat spikelet density.
AB - Bread wheat (Triticum aestivum) spike architecture is an important agronomic
trait. The Q gene plays a key role in the domestication of bread wheat spike
architecture. However, the regulatory mechanisms of Q expression and
transcriptional activity remain largely unknown. In this study, we show that
overexpression of bread wheat tae-miR172 caused a speltoid-like spike phenotype,
reminiscent of that in wheat plants with the q gene. The reduction in Q
transcript levels in the tae-miR172 overexpression transgenic bread wheat lines
suggests that the Q expression can be suppressed by tae-miR172 in bread wheat.
Indeed, our RACE analyses confirmed that the Q mRNA is targeted by tae-miR172 for
cleavage. According to our analyses, the Q protein is localized in nucleus and
confers transcriptional repression activity. Meanwhile, the Q protein could
physically interact with the bread wheat transcriptional co-repressor TOPLESS
(TaTPL). Specifically, the N-terminal ethylene-responsive element binding factor
associated amphiphilic repression (EAR) (LDLNVE) motif but not the C-terminal EAR
(LDLDLR) motif of Q protein mediates its interaction with the CTLH motif of
TaTPL. Moreover, we show that the N-terminal EAR motif of Q protein is also
essentially required for the transcriptional repression activity of Q protein.
Taken together, we reveal the functional regulation of Q protein by tae-miR172
and transcriptional co-repressor TaTPL in controlling the bread wheat spike
architecture.
PMID- 28703467
TI - Genetic changes in a novel breeding population of Brassica napus synthesized from
hundreds of crosses between B. rapa and B. carinata.
AB - Introgression of genomic variation between and within related crop species is a
significant evolutionary approach for population differentiation, genome
reorganization and trait improvement. Using the Illumina Infinium Brassica 60K
SNP array, we investigated genomic changes in a panel of advanced generation new
type Brassica napus breeding lines developed from hundreds of interspecific
crosses between 122 Brassica rapa and 74 Brassica carinata accessions, and
compared them with representative accessions of their three parental species. The
new-type B. napus population presented rich genetic diversity and abundant novel
genomic alterations, consisting of introgressions from B. rapa and B. carinata,
novel allelic combinations, reconstructed linkage disequilibrium patterns and
haplotype blocks, and frequent deletions and duplications (nonrandomly
distributed), particularly in the C subgenome. After a much shorter, but very
intensive, selection history compared to traditional B. napus, a total of 15
genomic regions with strong selective sweeps and 112 genomic regions with
putative signals of selective sweeps were identified. Some of these regions were
associated with important agronomic traits that were selected for during the
breeding process, while others were potentially associated with restoration of
genome stability and fertility after interspecific hybridization. Our results
demonstrate how a novel method for population-based crop genetic improvement can
lead to rapid adaptation, restoration of genome stability and positive responses
to artificial selection.
PMID- 28703468
TI - Escherichia coli isolates from commercial chicken meat and eggs cause sepsis,
meningitis and urinary tract infection in rodent models of human infections.
AB - The zoonotic potential of Escherichia coli from chicken-source food products is
important to define for public health purposes. Previously, genotypic and
phenotypic screening of E. coli isolates from commercial chicken meat and shell
eggs identified some E. coli strains that by molecular criteria resembled human
source extraintestinal pathogenic E. coli (ExPEC). Here, to clarify the zoonotic
risk of such chicken-source E. coli, we compared selected E. coli isolates from
chicken meat and eggs, stratified by molecularly defined ExPEC status, to human
source ExPEC and to laboratory E. coli for virulence in rodent models of sepsis,
meningitis and UTI, and evaluated whether specific bacterial characteristics
predict experimental virulence. Multiple chicken-source E. coli resembled human
source ExPEC in their ability to cause one or multiple different ExPEC-associated
infections. Swimming ability corresponded with urovirulence, K1 capsule
corresponded with ability to cause neonatal meningitis, and biofilm formation in
urine corresponded with ability to cause sepsis. In contrast, molecularly defined
ExPEC status and individual genotypic traits were uncorrelated with ability to
cause sepsis, and neither complement sensitivity nor growth in human urine
corresponded with virulence in any infection model. These findings establish that
chicken-derived food products contain E. coli strains that, in rodent models of
multiple human-associated ExPEC infections, are able to cause disease comparably
to human-source E. coli clinical isolates, which suggests that they may pose a
significant food safety threat. Further study is needed to define the level of
risk they pose to human health, which if appreciable would justify efforts to
monitor for and reduce or eliminate them.
PMID- 28703469
TI - Siderophore production in Azotobacter vinelandii in response to Fe-, Mo- and V
limitation.
AB - Azotobacter vinelandii is a terrestrial diazotroph well studied for its
siderophore production capacity and its role as a model nitrogen fixer. In
addition to Fe, A. vinelandii siderophores are used for the acquisition of the
nitrogenase co-factors Mo and V. However, regulation of siderophore production by
Mo- and V-limitation has been difficult to confirm and knowledge of the full
suite of siderophores synthesized by this organism has only recently become
available. Using this new information, we conducted an extensive study of
siderophore production in N2 -fixing A. vinelandii under a variety of trace metal
conditions. Our results show that under Fe-limitation the production of all
siderophores increases, while under Mo-limitation only catechol siderophore
production is increased, with the strongest response seen in protochelin. We also
find that the newly discovered A. vinelandii siderophore vibrioferrin is almost
completely repressed under Mo- and V-limitation. An examination of the potential
nitrogen 'cost' of siderophore production reveals that investments in siderophore
N can represent as much as 35% of fixed N, with substantial differences between
cultures using the Mo- as opposed to the less efficient V-nitrogenase.
PMID- 28703470
TI - Targeting hardcore smokers: The effects of an online tailored intervention, based
on motivational interviewing techniques.
AB - OBJECTIVES: Hardcore smokers have smoked for many years and do not intend to
quit. They also seem unreceptive to information about smoking cessation. We
developed a 30-min, tailored web-based intervention that includes motivational
interviewing principles. It aims to increase hardcore smokers' intention to quit
and their receptivity to information about smoking cessation. DESIGN: In a two
arm experiment, we compared outcome scores of the experimental intervention (n =
346) with those of a control intervention (n = 411). METHODS: Our main outcomes
were receptivity to information about quitting, intention to quit, quitting self
efficacy, and interest in a subsequent online intervention. Our secondary
outcomes were cigarettes smoked per day and quit attempts. All outcomes were
measured directly post-experiment (t1 ), after 2 weeks (t2 ), and after 2 months
(t3 ). RESULTS: At t1 , hardcore smokers in the intervention condition were more
receptive to information about quitting than controls. At both t2 and t3 , those
in the experimental group had reduced the number of cigarettes more than those in
the control group. At t2 , but not t3 , more participants in the experimental
group had reduced their cigarette consumption by at least 50% than among
controls. We found no significant differences in intention to quit, quitting self
efficacy, interest in a subsequent online quitting intervention, and number of
quit attempts. CONCLUSIONS: The intervention increased hardcore smokers'
receptivity to information about smoking cessation and decreased their cigarette
consumption by about 1 cigarette per day. Although the results are positive, the
clinical relevance may be limited. We recommend further developing this
intervention for practical use in health care settings. Statement of contribution
What is already known on this subject? Hardcore smokers have smoked for many
years and do not intend to quit. There are currently no online interventions for
hardcore smokers. What does this study add? This study tested an online
intervention for hardcore smokers. The intervention increased hardcore smokers'
receptivity to information about quitting. It also helped to reduce the number of
cigarettes per day.
PMID- 28703471
TI - Telling young children they have a reputation for being smart promotes cheating.
AB - The present research examined the consequences of telling young children they
have a reputation for being smart. Of interest was how this would affect their
willingness to resist the temptation to cheat for personal gain as assessed by a
temptation resistance task, in which children promised not to cheat in the game.
Two studies with 3- and 5-year-old children (total N = 323) assessed this
possibility. In Study 1, participants were assigned to one of three conditions: a
smart reputation condition in which they were told they have a reputation for
being smart, an irrelevant reputation control condition, or a no reputation
control condition. Children in the smart reputation condition were significantly
more likely to cheat than their counterparts in either control condition. Study 2
confirmed that reputational concerns are indeed a fundamental part of our smart
reputation effect. These results suggest that children as young as 3 years of age
are able to use reputational cues to guide their behavior, and that telling young
children they have a positive reputation for being smart can have negative
consequences.
PMID- 28703472
TI - Depth-resolved multimodal imaging: Wavelength modulated spatially offset Raman
spectroscopy with optical coherence tomography.
AB - A major challenge in biophotonics is multimodal imaging to obtain both
morphological and molecular information at depth. We demonstrate a hybrid
approach integrating optical coherence tomography (OCT) with wavelength modulated
spatially offset Raman spectroscopy (WM-SORS). With depth colocalization obtained
from the OCT, we can penetrate 1.2-mm deep into strong scattering media (lard) to
acquire up to a 14-fold enhancement of a Raman signal from a hidden target
(polystyrene) with a spatial offset. Our approach is capable of detecting both
Raman and OCT signals for pharmaceutical particles embedded in turbid media and
revealing the white matter at depth within a 0.6-mm thick brain tissue layer.
This depth resolved label-free multimodal approach is a powerful route to analyze
complex biomedical samples.
PMID- 28703473
TI - Service user involvement in the coproduction of a mental health nursing metric:
The Therapeutic Engagement Questionnaire.
AB - Service users' involvement in mental health service research is increasingly
acknowledged as important, yet, whilst involving users of mental health services
as research participants is commonplace, seeking out their experience and indeed
their "expertise" to facilitate the development of tools to be used within mental
health services is in its infancy. This article describes the involvement and
views of service users in the development of a nursing metric-the Therapeutic
Engagement Questionnaire. It presents their role in the three stages of
development: generation, statement reduction and authentication.
PMID- 28703474
TI - Hunger, craving and appetite.
PMID- 28703475
TI - Feasibility of CBCT-based dose with a patient-specific stepwise HU-to-density
curve to determine time of replanning.
AB - PURPOSE: (a) To investigate the accuracy of cone-beam computed tomography (CBCT)
derived dose distributions relative to fanbeam-based simulation CT-derived dose
distributions; and (b) to study the feasibility of CBCT dosimetry for guiding the
appropriateness of replanning. METHODS AND MATERIALS: Image data corresponding to
40 patients (10 head and neck [HN], 10 lung, 10 pancreas, 10 pelvis) who
underwent radiation therapy were randomly selected. Each patient had both
intensity-modulated radiation therapy and volumetric-modulated arc therapy plans;
these 80 plans were subsequently recomputed on the CBCT images using a patient
specific stepwise curve (Hounsfield units-to-density). Planning target volumes
(PTVs; D98%, D95%, D2%), mean dose, and V95% were compared between simulation-CT
derived treatment plans and CBCT-based plans. Gamma analyses were performed using
criterion of 3%/3 mm for three dose zones (>90%, 70%~90%, and 30%~70% of maximum
dose). CBCT-derived doses were then used to evaluate the appropriateness of
replanning decisions in 12 additional HN patients whose plans were previously
revised during radiation therapy because of anatomic changes; replanning in these
cases was guided by the conventional observed source-to-skin-distance change
derived approach. RESULTS: For all disease sites, the difference in PTV mean dose
was 0.1% +/- 1.1%, D2% was 0.7% +/- 0.1%, D95% was 0.2% +/- 1.1%, D98% was 0.2%
+/- 1.0%, and V95% was 0.3% +/- 0.8%; For 3D dose comparison, 99.0% +/- 1.9%,
97.6% +/- 4.4%, and 95.3% +/- 6.0% of points passed the 3%/3 mm criterion of
gamma analysis in high-, medium-, and low-dose zones, respectively. The CBCT
images achieved comparable dose distributions. In the 12 previously replanned 12
HN patients, CBCT-based dose predicted well changes in PTV D2% (Pearson linear
correlation coefficient = 0.93; P < 0.001). If 3% of change is used as the
replanning criteria, 7/12 patients could avoid replanning. CONCLUSIONS: CBCT
based dose calculations produced accuracy comparable to that of simulation CT.
CBCT-based dosimetry can guide the decision to replan during the course of
treatment.
PMID- 28703476
TI - In vitro biocompatibility of hydroxyapatite-added GIC: An SEM study using human
periodontal ligament fibroblasts.
AB - OBJECTIVE: Nano-hydroxyapatite-added GIC has been developed to improve the
physical properties of conventional GIC. However, biological response of
periodontal cells to this potentially useful cervical restorative material has
been unexplored. The aim of this study was to investigate the in vitro response
of human periodontal ligament fibroblasts to hydroxyapatite-added GIC. MATERIALS
AND METHODS: Three categories of materials, namely, test group 1 (cGIC or type IX
GIC), test group 2 (HA-GIC or hydroxyapatite-added GIC), and positive control
(glass cover slips) were incubated with human periodontal ligament fibroblasts.
The samples were viewed under scanning electron microscope to study the
morphological characteristics of fibroblasts. Additionally, elemental analysis
was performed to differentiate between the two test groups based on surface
chemical composition. RESULTS: Test group 1 (cGIC) exhibited cells with curled up
morphology, indicative of poor attachment to the substrate. Test group 2 (Ha-GIC)
exhibited cells with flattened morphology and numerous cellular extensions such
as lamellipodia and blebs, indicative of good attachment to the substrate. The
test group 2 (Ha-GIC) demonstrated higher surface elemental percentages of
calcium and phosphorus. CONCLUSION: Within the limitations of this study, it may
be concluded that hydroxyapatite-added GIC is more biocompatible than
conventional GIC (type IX), probably attributed to high elemental percentages of
calcium and phosphorus. CLINICAL SIGNIFICANCE: The search for an ideal cervical
restorative dental material has been ever elusive. Hydroxyapatite-added GIC is a
simple and economical dental material to fabricate from basic conventional GIC.
The results from this study strengthen its candidature for cervical and root
surface restorations which may later require soft tissue augmentation. The
possibility of connective tissue adhesion to this material is an exciting
prospect in the field of periorestorative dentistry.
PMID- 28703477
TI - A cost analysis of a long-term prospective study of patients treated with
immediately loaded implant-supported mandibular overdentures.
AB - BACKGROUND: The economic burden for patients seeking treatment with implant
supported prostheses has not been given adequate attention. PURPOSE: To document
long-term costs from a prospective trial on edentulous patients treated with
mandibular implant-supported overdentures and 2 loading protocols. MATERIALS AND
METHODS: The direct clinical and time costs for 35 patients receiving an
immediate-loading protocol (ILP) and 40 patients with a conventional-loading
protocol, over 14 years of observation, were analyzed in 2016 Canadian dollars as
a base year. Quality of life (QoL) for the ILP was measured using the OHIP-20
questionnaire. RESULTS: The ILP was associated with higher complication costs
($870.77 +/- 692.24 vs $85.73 +/- 133.14) with resultant higher maintenance costs
($1746.37 +/- 892.68 vs $853.04 +/- 276.21) (P < .05). OHIP results showed a
sustained improvement in QoL through the first 5 year of follow-up. A worsening
of QoL, specifically the functional-related OHIP scores, was noted at 14 years.
Incremental cost-effectiveness ratios indicated that the accrued maintenance
costs for the ILP made the treatment less cost-effective over time. CONCLUSIONS:
This long-term study confirmed that ILP is associated with higher maintenance
costs and varying subjective QoL measurements. Clinical treatment protocols
should be evaluated over a long period and address different perspectives.
PMID- 28703478
TI - Randomized clinical trial for the biological evaluation of two nanostructured
biphasic calcium phosphate biomaterials as a bone substitute.
AB - BACKGROUND: The presence of nonresorbable residual granules of hydroxyapatite
(HA) may decrease the bone/implant interface. To balance resorption and bone
formation biphasic calcium phosphate ceramics compounds applied at different
rates have been studied. PURPOSE: The aim of this trial was to compare the
clinical, histological, and histomorphometric responses of two new biphasic
calcium phosphate biomaterials in fresh dental sockets after 3 and 6 months.
MATERIALS AND METHODS: Forty-eight volunteers were divided randomly and double
blindly into 4 groups of 12 individuals: Clot (C), BoneCeramic (BC), Biomaterial
1 (B1), and Biomaterial 2 (B2) groups. Three and six months later, samples were
obtained, and histological and histomorphometric sections were evaluated,
focusing on the presence of fibrous connective tissue (CT) and newly formed bone.
Statistical analysis was performed (P < .05%). RESULTS: The quantification of
crystalline phases showed B1 composed of HA (60.28%) and beta-TCP (39.72%); B2
composed of HA (78.21%) and beta-TCP (21.79%); and BC composed of HA (61%) and
beta-TCP (39%). The B1 group showed the most newly formed bone (69.3% +/- 6.03%),
followed by the BC (51.6 +/- 12.34%), B2 (46.6 +/- 7.66%), and C groups (45.4 +/-
7.98%), and less connective tissue and biomaterial remained in the B1 group after
6 months. CONCLUSION: B1 group showed the greatest amount of newly formed bone
after 6 months.
PMID- 28703479
TI - Examination of DSM-5 Section III avoidant personality disorder in a community
sample.
AB - The current research evaluated the continuity between DSM-5 Section II and
Section III diagnostic operationalizations of avoidant personality disorder
(AvPD). More specifically, the study had three aims: (1) to examine which
personality constructs comprise the optimal trait constellation for AvPD; (2) to
investigate the utility of the proposed structure of the Section III AvPD
diagnosis, in regard to combining functional impairment (criterion A) and a
dimensional measure of personality (criterion B) variables; and (3) to determine
whether AvPD-specific impairment confers incremental meaningful contribution
above and beyond general impairment in personality functioning. A mixed sample of
402 university and community participants was recruited, and they were
administered multiple measures of Section II PD, personality traits, and
personality impairment. A latent measurement model approach was used to analyse
data. Results supported the general continuity between Section II and Section III
of the DSM-5; however, three of the four main criterion B traits were the
stronger predictors. There was also some support for the trait unassertiveness
augmenting the criterion B trait profile. The combination of using functional
impairment criteria (criterion A) and dimensional personality constructs
(criterion B) in operationalizing AvPD was supported; however, the reliance of
disorder-specific over general impairment for criterion A was not supported.
Copyright (c) 2017 John Wiley & Sons, Ltd.
PMID- 28703480
TI - Walking in the shoes of caregivers of children with obesity: supporting
caregivers in paediatric weight management.
AB - To incorporate the perspectives and experiences of family caregivers of children
with obesity, the KidFit Health and Wellness Clinic, a paediatric weight
management programme, embedded feedback opportunities into various stages of
programme development. Caregivers were eligible to participate if their children
had completed initial 4-week group-based pilot programming or were currently
receiving treatment in 10 or 12 week group-based programming. Data were collected
through feedback session discussions, audio-recorded, transcribed verbatim and
analysed thematically. In total, 6 caregivers participated in the pilot group
feedback session and 32 caregivers participated in the structured group feedback
sessions. Caregivers reported that healthy lifestyle strategies first
communicated by clinic staff to children during group sessions provided expert
validation and reinforcement when discussing similar messages at home. Caregivers
reported feeling isolated and blamed for causing their children's obesity and
appreciated the supportive forum that group-based programming provided for
sharing experiences. Since experiences of blame and isolation can burden
caregivers of children with obesity, paediatric weight management programmes
might consider including peer support opportunities and discussion forums for
ongoing social support in addition to education about lifestyle change.
PMID- 28703481
TI - Three-year clinical prospective follow-up of extrasinus zygomatic implants for
the rehabilitation of the atrophic maxilla.
AB - BACKGROUND: Placement of extrasinus zygomatic implants to support implant
supported rehabilitation is still controversial due to the scarcity of data.
PURPOSE: To evaluate the clinical outcomes of 94 extrasinus zygomatic implants,
installed laterally to the maxillary sinus, for rehabilitation of the edentulous
atrophic maxillae. MATERIALS AND METHODS: A total of 42 patients (mean age 58
years) with severely atrophic maxillae were treated between November 2010 and
July 2011, and followed up until July 2014. A total of 273 implants (94 zygomatic
implants and 179 conventional implants) were used. The patients were followed in
a standardized clinical and radiographic method. RESULTS: During the 3-year study
period, 1 zygomatic implant and 4 conventional implants failed, resulting in a
survival rate of 98.9% and 97.7% respectively. All restorations with titanium
welded bars were installed either 3 days after surgery (immediate loading) or 6
months after surgery (delayed loading), and were successful until the last follow
up appointment, except for minor technical problems. No patient presented any
type of sinus adverse event. No other significant occurrences were reported.
CONCLUSION: This 3-year clinical follow-up study indicates that extrasinus
zygomatic implants represent predictable treatment option atrophic maxillae.
Further longitudinal prospective clinical studies are necessary to confirm these
results.
PMID- 28703482
TI - Unique Solid-State Emission Behavior of Aromatic Difluoroboronated beta-Diketones
as an Emitter in Organic Light-Emitting Devices.
AB - Aromatic difluoroboronated beta-diketone (BF2 DK) derivatives are a widely known
class of luminescent organic materials that exhibit high photoluminescent quantum
efficiency and unique aggregation-dependent fluorescence behavior. However, there
have been only a few reports on their use in solid-state electronic devices, such
as organic light-emitting devices (OLEDs). Herein, we investigated the solid
state properties and OLED performance of a series of pi-extended BF2 DK
derivatives that have previously been shown to exhibit intense fluorescence in
the solution state. The BF2 DK derivatives formed exciplexes with a carbazole
derivative and exhibited thermally activated delayed fluorescence (TADF) behavior
to give orange electroluminescence with a peak external quantum efficiency of 10
% that apparently exceeds the theoretical efficiency limit of conventional
fluorescent OLEDs (7.5 %), assuming a light out-coupling factor of 30 %.
PMID- 28703483
TI - Photoinduced Electron Transfer-based Halogen-free Photosensitizers: Covalent meso
Aryl (Phenyl, Naphthyl, Anthryl, and Pyrenyl) as Electron Donors to Effectively
Induce the Formation of the Excited Triplet State and Singlet Oxygen for BODIPY
Compounds.
AB - Pristine BODIPY compounds have negligible efficiency to generate the excited
triplet state and singlet oxygen. In this report, we show that attaching a good
electron donor to the BODIPY core can lead to singlet oxygen formation with up to
58 % quantum efficiency. For this purpose, BODIPYs with meso-aryl groups (phenyl,
naphthyl, anthryl, and pyrenyl) were synthesized and characterized. The
fluorescence, excited triplet state, and singlet oxygen formation properties for
these compounds were measured in various solvents by UV/Vis absorption, steady
state and time-resolved fluorescence methods, as well as laser flash photolysis
technique. In particular, the presence of anthryl and pyrenyl showed substantial
enhancement on the singlet oxygen formation ability of BODIPY with up to 58 % and
34 % quantum efficiency, respectively, owing to their stronger electron-donating
ability. Upon the increase in singlet oxygen formation, the fluorescence quantum
yield and lifetime values of the aryl-BODIPY showed a concomitant decrease. The
increase in solvent polarity enhances the singlet oxygen generation but decreases
the fluorescence quantum yield. The results are explained by the presence of
intramolecular photoinduced electron transfer from the aryl moiety to BODIPY
core. This method of promoting T1 formation is very different from the
traditional heavy atom effect by I, Br, or transition metal atoms. This type of
novel photosensitizers may find important applications in organic oxygenation
reactions and photodynamic therapy of tumors.
PMID- 28703484
TI - Sulfonylureas as Concomitant Insulin Secretagogues and NLRP3 Inflammasome
Inhibitors.
AB - Insulin-secretory sulfonylureas are widely used, cost-effective treatments for
type 2 diabetes (T2D). However, pancreatic beta-cells are continually depleted as
T2D progresses, thereby rendering the sulfonylurea drug class ineffective in
controlling glycaemia. Dysregulation of the innate immune system via activation
of the NLRP3 inflammasome, and the consequent production of interleukin-1beta,
has been linked to pancreatic beta-cell death and multiple inflammatory
complications of T2D disease. One proposed strategy for treating T2D is the use
of sulfonylurea insulin secretagogues that are also NLRP3 inhibitors. We report
the synthesis and biological evaluation of nine sulfonylureas that inhibit NLRP3
activation in murine bone-marrow- derived macrophages in a potent, dose-dependent
manner. Six of these compounds inhibited NLRP3 at nanomolar concentrations and
can also stimulate insulin secretion from a murine pancreatic cell line (MIN6).
These novel compounds possess unprecedented dual modes of action, paving the way
for a new generation of sulfonylureas that may be useful as therapeutic
candidates and/or tool compounds in T2D and its associated inflammatory
complications.
PMID- 28703485
TI - Stereoselective Synthesis of Pillar[4]arene[1]cis-diepoxy-p-dione and X-Ray
Crystal Structure of Host-Guest System.
AB - Herein, we successfully develop a novel route to give rise to polarity for the
pillararenes by the introduction of oxygenated functionalities into
pillar[5]arene to stereoselectively synthesize the pillar[4]arene[1]cis-diepoxy-p
dione. Its host-guest properties with different dinitrile molecules were also
investigated and characterized by NMR and X-ray crystallography.
PMID- 28703486
TI - Pathogen screening and prognostic factors in children with severe ARDS of
pulmonary origin.
AB - BACKGROUND: Acute respiratory distress syndrome (ARDS) is one of the most lethal
diseases encountered in the pediatric intensive care unit (PICU). The etiological
pathogens and prognostic factors of severe ARDS of pulmonary origin in children
with respiratory virus infections were prospectively investigated. METHODS:
Enrolled children fulfilled the following criteria: (1) PICU admission; (2) age
of 1 month to 16 years; (3) diagnosis of infectious pneumonia and respiratory
virus infection; and (4) development of severe ARDS within 72 h after PICU
admission. Pathogens were detected in the blood and tracheal lavage fluid using
molecular techniques and a conventional culture system. The serum levels of
inflammatory mediators on the day of PICU admission were examined. RESULTS: Fifty
seven patients (32 boys; median age, 9 months) were enrolled. Multiple virus
infections, co-infection with bacteria/fungus, and bacteremia/fungemia were
observed in 60%, 49%, and 32% of children, respectively. Adenovirus-B, measles
virus, and cytomegalovirus were detected predominantly in tracheal lavage fluid.
There were no statistically significant differences between non-survivors and
survivors regarding the types of pathogen, incidence of multiple virus infection,
gender, age, clinical features, and treatment. The serum levels of interferon
(IFN)-gamma and the IFN-gamma/interleukin (IL)-10 ratio were higher in non
survivors. CONCLUSIONS: IFN-gamma upregulation as detected on the day of PICU
admission was found to be one of the possible prognostic factors affecting a
fatal outcome. These results suggest that modulation of inflammatory responses is
critical for the clinical management of children with ARDS.
PMID- 28703487
TI - Increasing awareness with recognition of pulsatile tinnitus for nurse
practitioners in the primary care setting: A case study.
AB - BACKGROUND AND PURPOSE: Pulsatile tinnitus is a whooshing sound heard synchronous
with the heartbeat. It is an uncommon symptom affecting fewer than 10% of
patients with tinnitus. It often goes unrecognized in the primary care setting.
Failure to recognize this symptom can result in a missed or delayed diagnosis of
a potentially life-threatening condition known as a dural arteriovenous fistula.
The purpose of this case study is to provide a structured approach to the
identification of pulsatile tinnitus and provide management recommendations.
METHOD: A case study and review of pertinent literature. CONCLUSIONS: Pulsatile
tinnitus usually has a vascular treatable cause. A comprehensive history and
physical examination will alert the nurse practitioner (NP) when pulsatile
tinnitus is present. Auscultation in specific areas of the head can detect
audible or objective pulsatile tinnitus. Pulsatile tinnitus that is audible to
the examiner is an urgent medical condition requiring immediate consultation and
referral. IMPLICATIONS FOR PRACTICE: Knowledge of pulsatile tinnitus and
awareness of this often treatable condition directs the NP to perform a detailed
assessment when patients present with tinnitus, directs appropriate referral for
care and treatment, and can reduce the risk of delayed or missed diagnosis.
PMID- 28703489
TI - Timed Delivery of Therapy Enhances Functional Muscle Regeneration.
AB - Cell transplantation is a promising therapeutic strategy for the treatment of
traumatic muscle injury in humans. Previous investigations have typically focused
on the identification of potent cell and growth factor treatments and
optimization of spatial control over delivery. However, the optimal time point
for cell transplantation remains unclear. Here, this study reports how myoblast
and morphogen delivery timed to coincide with specific phases of the inflammatory
response affects donor cell engraftment and the functional repair of severely
injured muscle. Delivery of a biomaterial-based therapy timed with the peak of
injury-induced inflammation leads to potent early and long-term regenerative
benefits. Diminished inflammation and fibrosis, enhanced angiogenesis, and
increased cell engraftment are seen during the acute stage following optimally
timed treatment. Over the long term, treatment during peak inflammation leads to
enhanced functional regeneration, as indicated by reduced chronic inflammation
and fibrosis along with increased tissue perfusion and muscle contractile force.
Treatments initiated immediately after injury or after inflammation had largely
resolved provided more limited benefits. These results demonstrate the importance
of appropriately timing the delivery of biologic therapy in the context of muscle
regeneration. Biomaterial-based timed delivery can likely be applied to other
tissues and is of potential wide utility in regenerative medicine.
PMID- 28703490
TI - Response to "Correspondence Concerning Hemocompatibility of Superhemophobic
Titania Surfaces".
PMID- 28703488
TI - Amniotic fluid neutrophils can phagocytize bacteria: A mechanism for microbial
killing in the amniotic cavity.
AB - PROBLEM: Neutrophils are capable of performing phagocytosis, a primary mechanism
for microbial killing. Intra-amniotic infection is characterized by an influx of
neutrophils into the amniotic cavity. Herein, we investigated whether amniotic
fluid neutrophils could phagocytize bacteria found in the amniotic cavity of
women with intra-amniotic infection. METHODS: Amniotic fluid neutrophils from
women with intra-amniotic infection were visualized by transmission electron
microscopy (n=6). The phagocytic activity of amniotic fluid neutrophils from
women with intra-amniotic infection and/or inflammation (n=10) or peripheral
neutrophils from healthy individuals (controls, n=3) was tested using ex vivo
phagocytosis assays coupled with live imaging. Phagocytosis by amniotic fluid
neutrophils was also visualized by confocal microscopy (n=10) as well as scanning
and transmission electron microscopy (n=5). RESULTS: (i) Intra-amniotic infection
related bacteria including cocci (eg Streptococcus agalactiae), bacilli (eg
Bacteriodes fragilis and Prevotella spp.), and small bacteria without a cell wall
(eg Ureaplasma urealyticum) were found inside of amniotic fluid neutrophils; (ii)
peripheral neutrophils (controls) rapidly phagocytized S. agalactiae, U.
urealyticum, Gardnerella vaginalis, and Escherichia coli; (iii) amniotic fluid
neutrophils rapidly phagocytized S. agalactiae and G. vaginalis; and (iv)
amniotic fluid neutrophils slowly phagocytized U. urealyticum and E. coli; yet,
the process of phagocytosis of the genital mycoplasma was lengthier. CONCLUSION:
Amniotic fluid neutrophils can phagocytize bacteria found in the amniotic cavity
of women with intra-amniotic infection, namely S. agalactiae, U. urealyticum, G.
vaginalis, and E. coli. Yet, differences in the rapidity of phagocytosis were
observed among the studied microorganisms. These findings provide a host defense
mechanism whereby amniotic fluid neutrophils can kill microbes invading the
amniotic cavity.
PMID- 28703492
TI - Comparison of a full systematic review versus rapid review approaches to assess a
newborn screening test for tyrosinemia type 1.
AB - BACKGROUND: Rapid reviews are increasingly used to replace/complement systematic
reviews to support evidence-based decision-making. Little is known about how this
expedited process affects results. OBJECTIVES: To assess differences between
rapid and systematic review approaches for a case study of test accuracy of
succinylacetone for detecting tyrosinemia type 1. METHODS: Two reviewers
conducted an "enhanced" rapid review then a systematic review. The enhanced rapid
review involved narrower searches, a single reviewer checking 20% of
titles/abstracts and data extraction, and quality assessment using an unadjusted
QUADAS-2. Two reviewers performed the systematic review with a tailored QUADAS-2.
Post hoc analysis examined rapid reviewing with a single reviewer (basic rapid
review). RESULTS: Ten papers were included. Basic rapid reviews would have missed
1 or 4 of these (dependent on which reviewer). Enhanced rapid and systematic
reviews identified all 10 papers; one paper was only identified in the rapid
review through reference checking. Two thousand one hundred seventy-six fewer
title/abstracts and 129 fewer full texts were screened during the enhanced rapid
review than the systematic review. The unadjusted QUADAS-2 generated more
"unclear" ratings than the adjusted QUADAS-2 [29/70 (41.4%) versus 16/70
(22.9%)], and fewer "high" ratings [22/70 (31.4%) versus 42/70 (60.0%)]. Basic
rapid reviews contained important inaccuracies in data extraction, which were
detected by a second reviewer in the enhanced rapid and systematic reviews.
CONCLUSIONS: Enhanced rapid reviews with 20% checking by a second reviewer may be
an appropriate tool for policymakers to expeditiously assess evidence. Basic
rapid reviews (single reviewer) have higher risks of important inaccuracies and
omissions.
PMID- 28703493
TI - Analysis of polychlorodibenzo-p-dioxins and polychlorodibenzofurans in stationary
source emissions in GC-MS/MS using hydrogen as the carrier gas.
AB - The European and American methods for the determination of polychlorodibenzo-p
dioxins and polychlorodibenzofurans in stationary source emissions require a high
resolution mass spectrometer detector. At the same time, all of the 17 toxic
2,3,7,8-chlorine-substituted isomers have to be separated by an appropriate
chromatographic method. The resulting analysis has long runtimes and sometimes a
double-column run is needed, which results in a huge waste of time, money and
manual labor. To obtain a fast and cost-effective but still reliable analytical
system, a single-column gas chromatography with hydrogen as carrier gas and
tandem mass spectrometry detection is proposed. The use of hydrogen as the
carrier gas is a good choice to shorten runtimes and improve the chromatographic
resolution, while tandem mass spectrometry is a well-known alternative for this
analysis. All the chromatographic and mass spectrometric parameters fill the
requirements of the reference methods with a 35% reduction of runtimes. The
accuracy is tested with three fly ash samples of a proficiency interlaboratory
test. A good correlation between the results is obtained (R2 = 0.992, slope =
0.9675), and no coelutions are noted. The system robustness is tested during 5
years of constant use and the maximal relative standard deviation of the relative
response factor is 18.8%.
PMID- 28703494
TI - Generating enzyme and radical-mediated bisubstrates as tools for investigating
Gcn5-related N-acetyltransferases.
AB - Gcn5-related N-acetyltransferases (GNATs) are found in all kingdoms of life and
catalyze important acyl transfer reactions in diverse cellular processes. While
many 3D structures of GNATs have been determined, most do not contain acceptor
substrates in their active sites. To expand upon existing crystallographic
strategies for improving acceptor-bound GNAT structures, we synthesized peptide
substrate analogs and reacted them with CoA in PA4794 protein crystals. We found
two separate mechanisms for bisubstrate formation: (a) a novel X-ray induced
radical-mediated alkylation of CoA with an alkene peptide and (b) direct
alkylation of CoA with a halogenated peptide. Our approach is widely applicable
across the GNAT superfamily and can be used to improve the success rate of
obtaining liganded structures of other acyltransferases.
PMID- 28703495
TI - Efficient Electron Transfer across a ZnO-MoS2 -Reduced Graphene Oxide
Heterojunction for Enhanced Sunlight-Driven Photocatalytic Hydrogen Evolution.
AB - The development of noble metal-free catalysts for hydrogen evolution is required
for energy applications. In this regard, ternary heterojunction nanocomposites
consisting of ZnO nanoparticles anchored on MoS2 -RGO (RGO=reduced graphene
oxide) nanosheets as heterogeneous catalysts show highly efficient photocatalytic
H2 evolution. In the photocatalytic process, the catalyst dispersed in an
electrolytic solution (S2- and SO32- ions) exhibits an enhanced rate of H2
evolution, and optimization experiments reveal that ZnO with 4.0 wt % of MoS2
RGO nanosheets gives the highest photocatalytic H2 production of 28.616 mmol h-1
gcat-1 under sunlight irradiation; approximately 56 times higher than that on
bare ZnO and several times higher than those of other ternary photocatalysts. The
superior catalytic activity can be attributed to the in situ generation of ZnS,
which leads to improved interfacial charge transfer to the MoS2 cocatalyst and
RGO, which has plenty of active sites available for photocatalytic reactions.
Recycling experiments also proved the stability of the optimized photocatalyst.
In addition, the ternary nanocomposite displayed multifunctional properties for
hydrogen evolution activity under electrocatalytic and photoelectrocatalytic
conditions owing to the high electrode-electrolyte contact area. Thus, the
present work provides very useful insights for the development of inexpensive,
multifunctional catalysts without noble metal loading to achieve a high rate of
H2 generation.
PMID- 28703491
TI - Week 96 results of the randomized, multicentre Maraviroc Switch (MARCH) study.
AB - OBJECTIVES: The Maraviroc Switch (MARCH) study week 48 data demonstrated that
maraviroc, a chemokine receptor-5 (CCR5) inhibitor, was a safe and effective
switch for the ritonavir-boosted protease inhibitor (PI/r) component of a two
nucleos(t)ide reverse transcriptase inhibitor [N(t)RTI] plus PI/r-based
antiretroviral regimen in patients with R5-tropic virus. Here we report the
durability of this finding. METHODS: MARCH, an international, multicentre,
randomized, 96-week open-label switch study, enrolled HIV-1-infected adults with
R5-tropic virus who were stable (> 24 weeks) and virologically suppressed [plasma
viral load (pVL) < 50 HIV-1 RNA copies/mL]. Participants were randomized to
continue their current PI/r-based regimen (PI/r) or to switch to MVC plus two
N(t)RTIs (MVC) (1:2 randomization). The primary endpoint was the difference in
the proportion with pVL < 200 copies/mL at 96 weeks. The switch arm was defined
as noninferior if the lower limit of the 95% confidence interval (CI) for the
difference was < -12% in the intention-to-treat (ITT) population. Safety
endpoints (the difference in the mean change from baseline or a comparison of
proportions) were analysed as key secondary endpoints. RESULTS: Eighty-two (PI/r)
and 156 (MVC) participants were randomized and included in the ITT analysis; 71
(87%) and 130 (83%) were in follow-up and on therapy at week 96. At week 96,
89.0% and 90.4% in the PI/r and MVC arms, respectively, had pVL < 50 copies/mL
(95% CI -6.6, 10.2). Moreover, in those switching away from PI/r, there were
significant reductions in mean total cholesterol (differences 0.31 mmol/L; P =
0.02) and triglycerides (difference 0.44 mmol/L; P < 0.001). Changes in CD4 T
cell count, renal function, and serious and nonserious adverse events were
similar in the two arms. CONCLUSIONS: MVC as a switch for a PI/r is safe and
effective at maintaining virological suppression while having significant lipid
benefits over 96 weeks.
PMID- 28703496
TI - The reliability and validity of ultrasound to quantify muscles in older adults: a
systematic review.
AB - This review evaluates the reliability and validity of ultrasound to quantify
muscles in older adults. The databases PubMed, Cochrane, and Cumulative Index to
Nursing and Allied Health Literature were systematically searched for studies. In
17 studies, the reliability (n = 13) and validity (n = 8) of ultrasound to
quantify muscles in community-dwelling older adults (>=60 years) or a clinical
population were evaluated. Four out of 13 reliability studies investigated both
intra-rater and inter-rater reliability. Intraclass correlation coefficient (ICC)
scores for reliability ranged from -0.26 to 1.00. The highest ICC scores were
found for the vastus lateralis, rectus femoris, upper arm anterior, and the trunk
(ICC = 0.72 to 1.000). All included validity studies found ICC scores ranging
from 0.92 to 0.999. Two studies describing the validity of ultrasound to predict
lean body mass showed good validity as compared with dual-energy X-ray
absorptiometry (r2 = 0.92 to 0.96). This systematic review shows that ultrasound
is a reliable and valid tool for the assessment of muscle size in older adults.
More high-quality research is required to confirm these findings in both clinical
and healthy populations. Furthermore, ultrasound assessment of small muscles
needs further evaluation. Ultrasound to predict lean body mass is feasible;
however, future research is required to validate prediction equations in older
adults with varying function and health.
PMID- 28703497
TI - Fast online replanning for interfraction rotation correction in prostate
radiotherapy.
AB - PURPOSE: To enable fast online replanning for prostate radiotherapy with the
inclusion of interfraction rotations and translations and investigate the
possibility for margin reduction via this regime. METHODS: Online daily
replanning for a 35-fraction treatment for five prostate cases is simulated while
accounting for anatomical transformations derived from fiducial marker data
available in our clinic. Two online replanning strategies were simulated,
compensating for: (a) rotation-only in combination with a couch shift and (b)
both translation and rotation without a couch shift. They were compared against
our current clinical protocol consisting of a single offline plan used over all
fractions with daily couch repositioning (translations only). For every patient,
the above methods were generated for several planning margins (0-8 mm with 2 mm
increments) in order to assess the performance of online replanning in terms of
target coverage and investigate the possible dosimetric benefit for the organs at
risk. The daily DVHs for each treatment strategy were used for evaluation and the
non tumor integral dose (NTID) for the different margins was calculated in order
to quantify the overall reduction of the delivered energy to the patient.
RESULTS: Our system is able to generate a daily automated prostate plan in less
than 2 min. For every patient, the daily treatment plans produce similar dose
distributions to the original approved plan (average CTV D99 relative difference:
0.2%). The inclusion of both shifts and rotations can be effectively compensated
via replanning among all planning margins (average CTV D99 difference: 0.01 Gy
between the two replanning regimes). Online replanning is able to maintain target
coverage among all margins, while - as expected - the conventional treatment plan
is increasingly affected by the interfraction rotations as the margins shrink
(average CTV D99 decrease: 0.2 Gy at 8 mm to 2.9 Gy at 0 mm margin). The possible
gain in total delivered energy to the patient was quantified by the decreased
NTID ranging from 12.6% at 6 mm to 32.9% at 0 mm. CONCLUSIONS: We demonstrate
that fast daily replanning can be utilized to account for daily rotations and
translations based on the daily positioning protocol. A daily plan can be
generated from scratch in less than 2 min making it suitable for online
application. Given the large magnitude of prostate rotation around the LR axis,
online correction for daily rotations can be beneficial even for the clinical 8
mm margin and could be utilized for treatments with small margin reduction mainly
limited then by anatomical deformations and intrafraction motion. Our online
replanning pipeline can be used in future treatments with online MR guidance that
can lead to further safe reduction of the planning margins.
PMID- 28703498
TI - Bayesian Networks to Compare Pest Control Interventions on Commodities Along
Agricultural Production Chains.
AB - The production of an agricultural commodity involves a sequence of processes:
planting/growing, harvesting, sorting/grading, postharvest treatment, packing,
and exporting. A Bayesian network has been developed to represent the level of
potential infestation of an agricultural commodity by a specified pest along an
agricultural production chain. It reflects the dependency of this infestation on
the predicted level of pest challenge, the anticipated susceptibility of the
commodity to the pest, the level of impact from pest control measures as
designed, and any variation from that due to uncertainty in measure efficacy. The
objective of this Bayesian network is to facilitate agreement between national
governments of the exporters and importers on a set of phytosanitary measures to
meet specific phytosanitary measure requirements to achieve target levels of
protection against regulated pests. The model can be used to compare the
performance of different combinations of measures under different scenarios of
pest challenge, making use of available measure performance data. A case study is
presented using a model developed for a fruit fly pest on dragon fruit in
Vietnam; the model parameters and results are illustrative and do not imply a
particular level of fruit fly infestation of these exports; rather, they provide
the most likely, alternative, or worst-case scenarios of the impact of measures.
As a means to facilitate agreement for trade, the model provides a framework to
support communication between exporters and importers about any differences in
perceptions of the risk reduction achieved by pest control measures deployed
during the commodity production chain.
PMID- 28703499
TI - New perspectives on familiar problems.
PMID- 28703500
TI - Medical students' view on managing sick patients.
PMID- 28703501
TI - The flipped classroom.
PMID- 28703502
TI - Handover education: student response.
PMID- 28703503
TI - OSVE or OSCE?
PMID- 28703504
TI - Efficacy of a Community- Versus Primary Care-Centered Program for Childhood
Obesity: TX CORD RCT.
AB - OBJECTIVE: This randomized controlled trial was conducted to determine
comparative efficacy of a 12-month community-centered weight management program
(MEND2-5 for ages 2-5 or MEND/CATCH6-12 for ages 6-12) against a primary care
centered program (Next Steps) in low-income children. METHODS: Five hundred forty
nine Hispanic and black children (BMI >= 85th percentile), stratified by age
groups (2-5, 6-8, and 9-12 years), were randomly assigned to MEND2-5 (27 contact
hours)/MEND/CATCH6-12 (121.5 contact hours) or Next Steps (8 contact hours).
Primary (BMI value at the 95th percentile [%BMIp95 ]) and secondary outcomes were
measured at baseline, 3 months (Intensive Phase), and 12 months (Transition
Phase). RESULTS: For age group 6-8, MEND/CATCH6-12 resulted in greater
improvement in %BMIp95 than Next Steps during the Intensive Phase. Effect size
(95% CI) was -1.94 (-3.88, -0.01) percentage points (P = 0.05). For age group 9
12, effect size was -1.38 (-2.87, 0.16) percentage points for %BMIp95 (P = 0.07).
MEND2-5 did not differentially affect %BMIp95 . Attendance averaged 52% and 22%
during the Intensive and Transition Phases. Intervention compliance was inversely
correlated to change in %BMIp95 during the Intensive Phase (P < 0.05). In the
Transition Phase, %BMIp95 was maintained or rebounded in both programs (P <
0.05). CONCLUSIONS: MEND/CATCH6-12 was more efficacious for BMI reduction at 3
months but not 12 months compared to Next Steps in underserved children.
Intervention compliance influenced outcomes, emphasizing the need for research in
sustaining family engagement in low-income populations.
PMID- 28703505
TI - Tanners' awareness and perceptions of legislation for tanning bed use.
PMID- 28703506
TI - Investigation of lithium distribution in the rat brain ex vivo using lithium-7
magnetic resonance spectroscopy and imaging at 17.2 T.
AB - Lithium is the first-line mood stabilizer for the treatment of patients with
bipolar disorder. However, its mechanisms of action and transport across the
blood-brain barrier remain poorly understood. The contribution of lithium-7
magnetic resonance imaging (7 Li MRI) to investigate brain lithium distribution
remains limited because of the modest sensitivity of the lithium nucleus and the
expected low brain concentrations in humans and animal models. Therefore, we
decided to image lithium distribution in the rat brain ex vivo using a turbo-spin
echo imaging sequence at 17.2 T. The estimation of lithium concentrations was
performed using a phantom replacement approach accounting for B1 inhomogeneities
and differential T1 and T2 weighting. Our MRI-derived lithium concentrations were
validated by comparison with inductively coupled plasma-mass spectrometry (ICP
MS) measurements ([Li]MRI = 1.18[Li]MS , R = 0.95). Overall, a sensitivity of
0.03 mmol/L was achieved for a spatial resolution of 16 MUL. Lithium distribution
was uneven throughout the brain (normalized lithium content ranged from 0.4 to
1.4) and was mostly symmetrical, with consistently lower concentrations in the
metencephalon (cerebellum and brainstem) and higher concentrations in the cortex.
Interestingly, low lithium concentrations were also observed close to the lateral
ventricles. The average brain-to-plasma lithium ratio was 0.34 +/- 0.04, ranging
from 0.29 to 0.39. Brain lithium concentrations were reasonably correlated with
plasma lithium concentrations, with Pearson correlation factors ranging from 0.63
to 0.90.
PMID- 28703507
TI - Successful laparoscopic treatment of advanced rectal cancer in an extremely
elderly man (101 years and 9 months).
AB - An extremely elderly man (age, 101 years and 9 months) visited our hospital
because of recurrent and worsening anal bleeding. Type 2 rectal cancer was found
in his rectum during colonoscopy. He did not have any severe coexisting diseases
and had not suffered any episodes of dementia. Laparoscopy-assisted anterior
resection combined with D2 lymph node dissection was performed with minimal
bleeding. The operation time was 128 min. The patient suffered mild reflux
pneumonia on postoperative day 6 and was administered additional antibiotics. He
recovered within 2 days. He was discharged on postoperative day 17, at which
point he was able to walk.
PMID- 28703509
TI - ?
PMID- 28703510
TI - [Precision medicine : a required approach for the general internist].
AB - The general internist cannot be a passive bystander of the anticipated medical
revolution induced by precision medicine. This latter aims to improve the
predictive and/or clinical course of an individual by integrating all biological,
genetic, environmental, phenotypic and psychosocial knowledge of a person. In
this article, national and international initiatives in the field of precision
medicine are discussed as well as the potential financial, ethical and
limitations of personalized medicine. The question is not to know if precision
medicine will be part of everyday life but rather to integrate early the general
internist in multidisciplinary teams to ensure optimal information and shared
decision process with patients and individuals.
PMID- 28703511
TI - [What is new in 2016 for the specialist in hospital internal medicine?]
AB - The year 2016 was rich in significant advances in all areas of internal medicine.
Many of them have an impact on our daily practice in general internal medicine.
From the treatment of NSTEMI in population older than 80, to new sepsis and
septic shock criteria to antidotes of new oral anticoagulants, this selection
offers to the readers a brief overview of the major advances. The chief residents
in the Service of internal medicine of the Lausanne University hospital are
pleased to share their readings.
PMID- 28703512
TI - [Recent developments in internal medicine].
AB - Whilst the practice of hospital based internal medicine is often carried out in
tight collaboration with clinical specialities, in particular for deciding on the
indication of interventional and diagnostic procedures, it is important to remain
objective with respect to the indications and benefits of these acts. This is the
case in areas such as cardiovascular medicine and nephrology. Recent studies also
have the potential to modify current guidelines for the management of arterial
hypertension and hypercholesterolemia. This article discusses some of these
selected subjects.
PMID- 28703513
TI - [2016 Update in general internal medicine : Good intentions, possible bad
outcomes].
AB - Ideally, our clinical practices and decisions should be based on evidence derived
from randomized clinical trials. Yet, we often have to determine the potential
side effects (including interactions) of drugs that we prescribed using other
level of evidence; clinical trials being obviously not appropriate for such
situations. Results from observational studies published in 2016 should be of
interest to primary care physicians. In this review, we present six of them. Once
the limitations of these non-interventional studies acknowledged, primary care
physicians should consider these results and be particularly attentive when
prescribing these drugs.
PMID- 28703514
TI - [2016 literature findings in internal general medicine].
AB - Treatment with diclofenac appears to be more effective compared to other NSAIDs
in the treatment of osteoarthritis of the large joints. Opioids do not diminish
significantly the pain in chronic lower back pain. Degenerative tears of the
meniscus, without signs of osteoarthritis, should be treated conservatively.
Acute appendicitis without perforation signs should be treated conservatively if
possible. Mindfulness meditation could prevent the recurrence of episodes in
major depression. Oropharyngeal exercises could reduce the frequency and
intensity of snoring. The choice of treatment in Helicobacter pylori infection
must consider its effectiveness and tolerance. Concomitant use of statins and
vitamin D could be an interesting alternative treatment in migraines.
PMID- 28703515
TI - [Raising the internist's know-how in the field of rare diseases: mitochondrial
diseases as an illustrative example].
AB - Rare Diseases, defined by a prevalence of less than 1 per 2000 persons, affect 36
million people in Europe, 500 000 in Switzerland, corresponding to 6-8% of the
general population. 7000 rare diseases are currently recorded.Mitochondrial
diseases are a heterogeneous group of genetic diseases. They are characterized by
intracellular failure of energy production and affect predominantly energy
dependent tissues. The clinical presentation is not always suggestive,
particularly in adulthood. In order to reach the diagnosis, a prerequisite is to
think of them. In this article, we will focus on the clinical aspects of
mitochondrial disorders in order to give the internist simple tools on how not to
miss those rare diseases in his daily practice.
PMID- 28703516
TI - ?
PMID- 28703517
TI - ?
PMID- 28703518
TI - ?
PMID- 28703520
TI - ?
PMID- 28703519
TI - ?
PMID- 28703521
TI - ?
PMID- 28703522
TI - ?
PMID- 28703523
TI - ?
PMID- 28703524
TI - ?
PMID- 28703525
TI - ?
PMID- 28703526
TI - [Addictions].
AB - In 2016, the actuality for addictions in this edition addresses four points.
Social neurosciences of addiction are of great importance regarding the
vulnerabilities for addiction and for the recovery. Deep brain stimulation is
emerging in the therapeutic panel coming from the clinical neurosciences for the
addictions. Novelties in opioid agonists for the treatment of opiates dependence,
with the apparition in the Swiss market of release morphine and of levomethadone.
Cannabis and prison, a pilot study for the maintenance of abstinence in prison.
PMID- 28703527
TI - [Non-celiac wheat sensitivity - growing evidence for a wheat-dependent immune
mediated disease].
AB - These past years, double-blinded placebo controlled food challenges in subjects
with irritable bowel syndrome (IBS) reporting sensitivity to gluten have
identified a group of individuals without celiac disease (CD) in whom symptoms
were clearly aggravated by wheat. Not only did the exposure to wheat trigger
intestinal symptoms, but also frequently fatigue and a sensation of foggy mind.
Recent studies in mice and sensitive subjects suggest an immune activation by
various wheat proteins, with a rapid increase of intestinal mucosal permeability
and recruitment of intraepithelial lymphocytes. Moreover, markers of epithelial
damage and immune activation are increased in the peripheral blood of wheat
sensitive subjects upon challenge, and decrease under gluten-free diet. Larger
studies are needed to better characterize this entity and to distinguish it from
food-aggravated IBS and a " forme fruste " of CD.
PMID- 28703528
TI - [Innovations in the treatment of severe asthma].
AB - In severe asthma, there is a real need for new effective therapies offering a
good safety and tolerance profile. Mepolizumab is a humanized anti-interleukin-5
monoclonal antibody, available in Switzerland since 2016 for treatment of severe
adult eosinophilic asthma. Other monoclonal antibodies, such as dupilumab, are
being developed in the field of asthma.
PMID- 28703529
TI - [Hope for chronic inflammatory diseases : the anti-IL-6 receptor monoclonal
antibody tocilizumab].
AB - Vasculitis like Horton's disease, some autoinflammatory syndromes (Behcet's,
Still's diseases) often require long term treatment with steroids, and therefore
are associated with non acceptable adverse events, especially when resistant to
treatment. Recently, a number of controlled prospective clinical trials are
supporting the interest of the anti-IL-6 receptor monoclonal antibody tocilizumab
in these chronic inflammatory conditions et may soon be recognized as second
intention therapeutic approach.
PMID- 28703530
TI - [News in Angiology and Hemostasis].
AB - Several themes were selected from those that marked the year 2016. The analysis
of registries with "real life" data regarding the use of direct oral
anticoagulants is reassuring and overall confirm the data of the pivotal studies.
We also present the validation of a prediction rule for risk stratification of
thromboembolism recurrence and duration of anticoagulation after an unprovoked
event. In addition, new data shed light on the treatment of distal vein
thrombosis. We also address the issue of venous thromboembolism risk related to
oral contraceptives and the issue of genetic testing prior prescription, and
finally present a new factor VIII recently available for the treatment of
patients with acquired hemophilia A.
PMID- 28703531
TI - [Cardiology update in 2016].
AB - In 2016 the European Society of Cardiology (ESC) published new guidelines. These
documents update the knowledge in various fields such as atrial fibrillation,
heart failure, cardiovascular prevention and dyslipidemia. Of course it is
impossible to summarize these guidelines in detail. Nevertheless, we decided to
highlight the major modifications, and to emphasize some key points that are
especially useful for the primary care physician.
PMID- 28703532
TI - [Novelties in surgery in 2016].
AB - The year 2016 allowed further implementation of previous years innovations with
the PIPAC treatment for peritoneal carcinomatosis, the development of new
surgical technologies and procedures and challenging general principles in
general and digestive surgery, including cholecystectomy and appendectomy.
Prevention, improved general and perioperative care (ERAS program) become an
integral part of our standard surgical activity.
PMID- 28703533
TI - [The dermatological indications of laser: beyond cosmetic target.]
AB - During the last 30 years, the use of lasers in dermatology has gone far beyond
the spectrum of aesthetic and cosmetic applications. Techniques are more than
simple removal by CO2 Laser. Increasing knowledge, understanding, and experience
have helped to effectively treat numerous important skin diseaes by the use of
lasers. However, high-quality clinical trials are sparse in this domain.
Consequently, so far only the treatment of hemangiomas and warts is a laser
indication reimbursed by insurance companies. This article discusses three types
of skin diseases where substantial progress has been reported in the scientific
literature in 2016, namely pigmentary disorders, vascular diseases, and
inflammatory dermatoses.
PMID- 28703534
TI - [News in diabetology 2016].
AB - The field of diabetes is constantly evolving, with numerous new molecules
reaching the market in the treatment of type 2 diabetes. Paradoxically, this drug
jungle is difficult for the primary care physician and can lead to therapeutic
inertia. After the beneficial effect of empagliflozin on cardiovascular outcomes
in the EMPA REG Outcome trial in 2015, liraglutide also shows cardiovascular
benefits in high risk patients with type 2 diabetes. Therefore, these two
studies, led to new recommendations by the Swiss Society for Endocrinology and
Diabetes, by notably favouring the prescription of these molecules to type 2
diabetic patients in secondary prevention, after metformin.
PMID- 28703535
TI - [Endocrinology, what's new in 2016].
AB - The European Society of Endocrinology has published this year a series of
guidelines for hypoparathyroidism, the management of adrenal incidentalomas as
well as for the long-term follow-up of patients operated on for a
phaeochromocytoma/paraganglioma (PPGL). For hypoparathyroidism, guidelines insist
on screening for chronic complications and monitoring treatment with calcium and
vitamin D; the use of recombinant PTH may provide new opportunities for the
future. Concerning adrenal incidentalomas, the panel of the guidelines primarily
recommends non contrast CT for the evaluation of the risk of malignancy. Patients
operated on for a PPGL, should be offered an individualized follow-up plan based
on assessment of their risk of tumor recurrence.
PMID- 28703536
TI - [Gastroenterology and hepatology in 2016].
AB - This article aims to detail the major innovations occurred in Gastro-enterology
in 2016, including the introduction of a new molecule, the vonoprazan, for the
treatment of refractory gastroesophagal reflux disease (GERD) and a new way of
eradication of H. pylori. The possibility to use an intermittent dose of PPI
rather than continuously in severe gastric and duodenal ulcers after successful
endoscopic hemostasis is also discussed as well as the withdrawal of
corticosteroids in the treatment of autoimmune pancreatitis. The formulation of
corticosteroids in the treatment of eosinophilic esophagitis, the interest of the
chromo-endoscopy during colonoscopy highlighting small polyps (from 1 to 5 mm = "
diminutive polyps ") and the introduction on the Swiss market for biosimilars in
the treatment of inflammatory bowel disease (IBD) are also discussed.
PMID- 28703537
TI - [Geriatric medicine].
AB - In 2016, consequences, contributing factors, and prevention of inappropriate drug
prescribing were investigated. Two studies lift the veil on unexplained falls and
syncope. A meta-analysis questions the need to adapting transfusion's threshold
to comorbidities, and another one the performance of screening for swallowing
disorders. The Framingham Heart Study reports the declining of the incidence of
vascular dementia. The role played by microbleeds in cognitive deterioration was
investigated and aducanumab showed encouraging effect in Alzheimer's disease.
When vaccination against influenza for health workers in nursing home was
challenged by a meta-analysis this recommendation must be followed. Vaccines
against shingles are effective and safe, and a study confirms the efficacy of the
HZ7su among 70+.
PMID- 28703538
TI - [Obstetric medicine : the success of a transdisciplinary approach to the maternal
health].
AB - Obstetric medicine is a specialty that addresses maternal health and medical
complications during pregnancy. This emerging specialty responds to the
increasing need for specialized intervention in cases of high risk pregnancies,
at a time when pregnancies can occur at more advanced ages and where advances in
therapeutics now allow to consider pregnancy in mothers with chronic illness.
Furthermore, medical conditions specific to pregnancy, such as hypertensive
disorders of pregnancy or gestational diabetes, are now recognized as emerging
risk factors for cardiovascular, metabolic and renal diseases, for which
longitudinal care beyond the maternity ward is of critical importance.
PMID- 28703539
TI - [Hypertension].
AB - The year 2016 has been impacted essentially by the results of the SPRINT trial
published in the end of 2015. This study proposed a systolic blood pressure
target of <120 mmHg for all high cardiovascular risk patients. In this review, we
shall discuss the impact of this trial and the criticisms that have appeared
following its publications. These latter will probably limit its practical
application. Moreover, we shall discuss the screening of hypertension in children
and adolescents and the possible role of drugs lowering uric acid in hypertensive
patients with hyperuricemia.
PMID- 28703540
TI - [One year of infectious diseases : a review].
AB - Several outbreaks have made the news in 2016 : Ebola has come at an end, Zika is
booming and a resurgence of yellow fever takes place in Africa. In Switzerland,
two hospital outbreaks have been reported, caused by Mycobacterium chimerae and
Burkholderia cepacia. A major new article has consolidated the notion that
prolonged antibiotic therapy is unnecessary in Lyme disease. As multiresistant
bacteria are increasing in frequency, innovative therapeutic approaches are under
development. For lung infections, sensitive and specific methods are in need to
refine their etiological diagnosis. In pneumonia, therapy can be shortened
without risk compared with usual practice. Finally, the epidemiology of bacterial
meningitis has changed in the last 10 years, with a decrease of incidence.
PMID- 28703541
TI - [Emergency medicine : updates 2016].
AB - Several articles have been published during 2016 suggesting amendments in certain
established practices of emergency medicine. Amongst such practices now in
question are : 1) the use in mechanical cardiopulmonary resuscitation of
amiodarone and lidocaine which appear not to improve survival or neurological
outcome ; 2) apneic oxygenation being associated with a significant increase in
first pass success intubation ; 3) an updating of the definition of sepsis and
septic shock which facilitate earlier identification of susceptible patients ; 4)
the use of the high sensitivity troponin 0-hour / 1-hour algorithm which
differentiates earlier patients with or without acute myocardial infarction ; 5)
that intramuscular non-steroidal anti-inflammatory drugs offer effective
sustained analgesia for renal colic, and finally 6) that irrigation of an abscess
cavity after incision and drainage is not beneficial.
PMID- 28703542
TI - [Nephrology : What's new in 2016 ?]
AB - The first treatment which slows the course of polycystic kidney disease is now
available in Switzerland. There is no benefit of immunosuppression when treating
IgA nephropathy. Rituximab has been proved effective in the treatment of
membranous nephropathy. When to start renal replacement therapy in acute kidney
injury ? The debate still continues. In selected patients with end-stage renal
failure, starting with twice a week hemodialysis is a desirable option.
Peritoneal dialysis can be considered in frail patients. Better being
transplanted with a HLA-incompatible living donor than to be on the waiting list.
Immunosuppression without a calcineurin inhibitor is a potential immunologic
hazard even for stable transplants. Long-term results of belatacept-based
immunosuppression instead of cyclosporin showed better graft and patient survival
but more acute rejection.
PMID- 28703543
TI - [Neurology].
AB - Aducanumab reduces the burden of amyloid plaques in Alzheimer's disease, with
significant improvement of clinical scores. Endovascular thrombectomy is
recommended in patients with acute stroke with proximal occlusion of the anterior
circulation. CGRP antagonists and botulinum toxin are effective in migraine. ZIKA
virus infection has been linked to the Guillain-Barre syndrome. Edaravone has
been approved for amyotrophic lateral sclerosis. Two monoclonal antibodies
(ocrelizumab and daclizumab) and siponimod show positive results in multiple
sclerosis. Thalamotomy of ventral intermediate nucleus (by gamma-knife or by
magnetic resonance-guided focused ultrasound) is effective in drug-resistant
essential tremor. The dose-dependent risk of foetal malformations associated with
valproate and topiramate is confirmed.
PMID- 28703544
TI - [Ophthalmology in 2016 : the advent of ocular biomarkers].
AB - Precision medicine is the future. In all fields of medicine, optimized therapy
aims at identifying individuals at risks in order to prevent diseases, to
identify specific molecular targets in a specific patient, at a specific time, to
administer optimized treatment with less side effects. To achieve this ambitious
aim, biomarkers, which should be specific and sensitive predictive indicators of
diseases, or of response to treatment or of a state of evolution of the disease,
must be identified. The eye offers an easy access organ to collect directly media
or tissue, which can serve to identify such markers. This paper summarizes recent
advances in the identification of ocular biomarkers of ocular diseases but also
of brain diseases.
PMID- 28703545
TI - [Osteoporosis].
AB - After one year of treatment with denosumab, the incidence of fracture is lower in
patients previously treated one year with romosozumab as compared with placebo.
Cessation of denosumab injections is followed by a rebound of bone resorption, a
decrease of bone mineral density and increased risk of multiple vertebral
fractures. For safety reasons, odanacatib, an inhibitor of cathepsine K and
consecutively of bone resorption will not be available. Abaloparatide, a
PTHrp(Parathormon related protein) analog, decreases the incidence of vertebral
and non vertebral fractures. In patients with diabetes, the incidence of
fractures is increased mainly due to alterations quality of bone.
PMID- 28703546
TI - [Novelties 2016 in pediatrics].
AB - Nutrition is central in pediatric care : essential for growth and development, it
plays also a role in the prevention of many diseases.Even if breastfeeding is
highly recommended, its implementation may be difficult in particular for
premature and ill newborns. The creation of a specific unit for breastfeeding
support in neonatology allows to help mothers willing to nurse and to improve the
rate of breastfeeding for these vulnerable infants.Eating disorders represent an
important challenge for patient care. Early detection and rapid management of
anorexia is essential for the prognosis. This article describes the challenges
and the practical process underlying the development of a practical guideline to
manage children and adolescents hospitalized for anorexia.
PMID- 28703547
TI - [New therapeutic options in pulmonary diseases in 2016 : focus on asthma, COPD
and idiopathic pulmonary fibrosis (IPF)].
AB - We chose, for this update on novelties in treatments for pulmonary disorders in
2016, to focus on advances in 3 pulmonary disorders : chronic obstructive
pulmonary disease (COPD), asthma and IPF. For COPD, the contribution of inhaled
glucocorticosteroids and roflumilast are revisited and the benefits obtained
through endoscopic volume reduction procedures are clarified. In asthma and IPF,
new molecules offer new hopes : a bettre control of exacerbations in asthma and a
stabilisation or slowing of disease progression in IPF.
PMID- 28703548
TI - [New developments in psychiatry].
AB - The development of the role of peer workers in mental health aims to give more
space to patients and to enrich mental health treatment with their personal
experience. New strategies have also been developed to facilitate access to work
for patients suffering from mental illness as well as to improve mental health of
workers, within a global movement aiming at putting forth the role of work as a
mean towards social integration, which tends to be forgotten in a society aiming
principally at productivity. In a more technical domain, repeated Transcranial
Magnetic Stimulation offers a new tool for the treatment of resistant depression.
Finally, the Swiss Society for Psychiatry and Psychotherapy (SGPP) has published
recommendations for the treatment of schizophrenia which are freely available on
the website of this society.
PMID- 28703549
TI - [Anti-IL-6 : new therapeutic trends].
AB - The anti-IL-6 tocilizumab is a recognized treatment in rheumatoid arthritis and
in systemic juvenile idiopathic arthritis. Almost ten years after its first use,
there is more information about its security profile and its indication should be
extended to other systemic inflammatory diseases, such as the giant cell
arteritis. New molecules targetting the IL-6 pathway are under validation :
sarilumab, sirukumab and olokizumab. Here is a brief state of the future outlook
and trends of this therapeutic class.
PMID- 28703550
TI - [Urology : therapeutics news in 2016].
AB - This article summarizes recent advances in the field of urinary infections,
bladder function, minimal invasive surgery and genitourinary cancers.
PMID- 28703551
TI - [Hospital readmissions: current problems and perspectives].
AB - Health systems in developed countries are facing the challenge of hospital
readmissions, part of which can be considered avoidable. The transition between
hospital stay and ambulatory care is a sensitive period in terms of continuity of
care and patient safety, and its failure could lead to increased readmissions
rate. Various measures have been proposed to reduce the risks associated with
this transition, and the combination of various interventions undertaken at all
stages of the care process, could reduce readmission rates. A multidisciplinary
approach, widely involving all health care providers, both at the hospital and
outpatient level, seems to be the key factor to success.
PMID- 28703552
TI - ?
PMID- 28703553
TI - ?
PMID- 28703554
TI - ?
PMID- 28703555
TI - ?
PMID- 28703556
TI - ?
PMID- 28703557
TI - ?
PMID- 28703558
TI - ?
PMID- 28703559
TI - [Long term complication of thoracoabdominal blunt trauma].
PMID- 28703560
TI - [Rectal polyps: all that glitters is not adenoma].
PMID- 28703561
TI - [Sacral neuromodulation. Long-term results].
AB - Sacral neuromodulation involves electrical stimulation of af-ferent nerve roots
to restore the balance between inhibitory and excitatory reflexes who improve the
functional activity of the pelvic floor. With benefits in patients with fecal
inconti-nence, constipation and chronic anorectal pain. Objective. The aim of
this study is present the results obtained with sacral neuromodulation for the
treatment of patients with fecal incontinence, severe and intractable chronic
constipa-tion and chronic anorectal pain. Patients and methods. 33 patients had
indication for transitory electrical sacral stimu-lation, 25 patients performed
transitory electrical stimula-tion for fecal incontinence, 5 with refractary
constipation and 3 with chronic anorectal pain. In cases of fecal inconti-nence,
the patients performed previous anorectal manometry and ultrasonography
examination of anal sphincters. When the constipation is the indication, we
performed stimulation in patients with severe and refractary constipation like
step before total colectomy. In cases of chronic anorectal pain, the electrical
transitory test was performed according to our treatment algorithm for management
of functional anorectal pain. In all cases, if the patients had satisfactory
results after 2 weeks period the definitive implant was placed. Results. Mean
follow-up was 69 months (range 6-130). Definitve implant was placed for treatment
of fecal incontinence in 23 patients with a decrease in fecal incontinence scores
in 98%, with an average success rate of 66% (range: 45-92). In cases of
constipation, 3 definitive implants were placed, the mean follow-up was 77 months
(range: 51-96) with a success rate between 50%-80% as measured by bowel
frequency. We performed definitive electrical stimulation in 3 patients wit
chronic and intractable anorectal pain. Response rates as measured by visual
analog scale were between 40%-70%. Conclusions. Sacral neuromodulation is an area
in constant growth, with more indications. The success depends on the correct
indication and the patients need to be treated with other therapeutic options
before sacral neuromodulation.
PMID- 28703562
TI - [Functional dyspepsia in students of eigth peruvians medical schools. Influence
of the habits].
AB - : Functional dyspepsia impacts on quality of life. Due to itsmultifactorial
etiology its characterization proves difficult,especially in populations at risk
such as medical students. Objetives: To determine if behavioral and harmful
habitsof medical students from eight universities of Peru wereassociated to
functional dyspepsia. Methods: Multicentric,cross-sectional study. A self
administered questionnaire was taken among students enrolled in eight medical
facultiesin Peru. Functional dyspepsia was measured using a validatedtest; diet
characteristics, alcohol, tobacco, coffee or energydrinks consumption were
considered behavioral habits.Furthermore, others from the social and educational
spherewere measured. Bivariate and multivariate statistical analyseswere made.
Results: From a total of 1.923 students, themedian of the ages was 20, 55% were
women and 24% sufferedfrom functional dyspepsia. Factors which diminishedthe
frequency of functional dyspepsia were masculine gender(aPR:0,75; 95%CI:0.64
0.87; p < 0,001), hours spentstudying (aPR:0,97; 95%CI:0,96-0,99; p < 0,001)
andeating following a fixed schedule (aPR:0,80; 95%CI:0,67-0,95; p = 0,013);
however, having failed a course increasesthe frequency of functional dyspepsia
(aPR:1.24;95%CI:1.13-1.37; p < 0,001)adjusted for age, as well asdifficulties to
fall asleep and depression. Conclusion: Manymedical students suffered from
functional dyspepsia, this beingrelated to several behavioral variables;
therefore furtherstudies as well as educational institutions' intervention is
required,due to the short and long term problems that mayarise from this
situation.
PMID- 28703563
TI - ?
PMID- 28703564
TI - Colorectal cancer screening in Latin America: Arewe still in the Stone Age?
PMID- 28703565
TI - [Teres ligament hemangioma: laparoscopicapproach].
AB - Hemangiomas are benign vascular tumors, whose origincomes from the embryonic
mesodermal tissue remains. The liver is the most common location. Its location in
the teresligament is extremely rare. This is a 59 years old male admittedbecause
of episodes of epigastric pain for six months.A CT scan and MRI demostrated a 2
cm diameter lesionlocated near the Teres ligament. Laparoscopic resection
wasperformed. Hemangiomas are the most common benign solidtumors located in the
liver. They represents 73% of all benignliver tumors. MRI is the imaging of
greater certainty fordiagnosis. The Teres ligament (ligamentum teres hepatis) isa
fibrous cord resulting in obliteration of the umbilical vein.The location of
hemangiomas in this region is extremely rarebut should be considered and should
make the differentialdiagnosis with a pedicled hepatic hemangioma or
gastointestinalstromal tumors.
PMID- 28703566
TI - [Adult intestinal no rotation].
AB - 90% of cases of intestinal obstruction caused by intestinalmalrotation occur in
children under 1 year of age, beingvery uncommon in adults. A female patient of
27 years ofage consults with abdominal pain, vomiting, abdominal
distention,dehydration and signs of severe malnutrition. After EGDS, CT scan, and
48 hours of clinical expectation, surgicalintervention was decided with diagnosis
of high intestinalobstruction. Intraoperative finding was no intestinal
rotationat all. Ladd's technique was performed together withprophylactic
appendectomy. Postoperative evolution wasfavorable. The rare presentation in
adults motivates the presentationof this case.
PMID- 28703567
TI - [Rapunzel syndrome as a cause ofobstruction and intestinal perforation].
AB - The following is a case report involving a 16 year old femalewith
trichotillomania as an antecedent. This patient presentedto the Emergency Room
with a chief complaint of earlysatiety and persistent abdominal pain for the past
3 months.However, recently her abdominal pain has worsened and itis now
complicated by nausea and vomiting. The physicalexam was notable for epigastric
pain on deep palpation. Thebiochemical analysis and abdominal ultrasound were
otherwiseunremarkable. An esophagogastroduodenoscopy wassubsequently performed
where a trichobezoar was discovered.It extended from the gastric fundus to the
third portion ofthe duodenum. A surgical extraction of the trichobezoar wasthen
performed. The trichobezoar was found to be 130 cmin length and 8 cm wide at its
most cephalad aspect. It isimportant to note that they also found five mall
perforationsthroughout the duodenum and jejunum. The patient wasdischarged with
outpatient follow up with psychiatry. In thisreport we describe the case of a
patient with Rapunzel syndromethat was complicated by small bowel perforation
andwe provide a review of the salient literature concerning thissyndrome and its
associated complications.
PMID- 28703568
TI - [An infrequent cause of iron-deficiencyanemia: Menetrier disease].
AB - Menetrier disease is a rare condition of an unknown origin,with a wide spectrum
of clinical signs and symptoms atpresentation. Diagnosis is made through the
combination ofclinical, analytical, endoscopic and histological data. Surgeryis
the classical treatment. However, new medical approacheshave emerged.
PMID- 28703569
TI - Ultrasensitive Electrochemiluminescence Biosensor for MicroRNA Detection by 3D
DNA Walking Machine Based Target Conversion and Distance-Controllable Signal
Quenching and Enhancing.
AB - In this study, an electrochemiluminescence (ECL) regenerated biosensor was
reported to sensitively detect microRNA through 3D DNA walking machine and "on
off-super on" strategy. First, 3D DNA walking machine with higher efficiency of
payload releasing and superior signal amplification than those of the traditional
DNA walking machine was initially introduced in the ECL system for converting
target microRNA to intermediate DNA and achieving significant signal
amplification. Second, the distance between CdS:Mn quantum dots and Au
nanoparticles was increased with the hybridization of intermediate DNA and Au
nanoparticles modified S2, which weakened the energy transfer for ECL signal
recovering and excited the surface plasma resonance for further enhancing the
signal to construct the on-off-super on biosensor. Such an on-off-super on
strategy not only reduced the ECL background signal but also increased the
detection sensitivity. Impressively, the elaborately designed biosensor could be
regenerated by Lambda exonuclease hydrolyzing the intermediate DNA to make Au
nanoparticles modified S2 recover to their original hairpin structure. With the
amazing signal amplification of 3D DNA walking machine and sensitive distance
control of the on-off-super on strategy, the biosensor showed excellent
performance for microRNA-141 detection with a low detection limit of 3.3 fM and
could be applied to human prostate cancer cells analysis. Furthermore, this work
established a foundation to apply 3D walker in ECL methodology and provided an
effective way for analysis of other microRNA or cancer cells.
PMID- 28703570
TI - Novel Fluorescent Microemulsion: Probing Properties, Investigating Mechanism, and
Unveiling Potential Application.
AB - Nanoscale microemulsions have been utilized as delivery carriers for
nutraceuticals and active biological drugs. Herein, we designed and synthesized a
novel oil in water (O/W) fluorescent microemulsion based on isoamyl acetate,
polyoxyethylene castor oil EL (CrEL), and water. The microemulsion emitted bright
blue fluorescence, thus exhibiting its potential for active drug detection with
label-free strategy. The microemulsion exhibited excitation-dependent emission
and distinct red shift with longer excitation wavelengths. Lifetime and quantum
yield of fluorescent microemulsion were 2.831 ns and 5.0%, respectively. An
excellent fluorescent stability of the microemulsion was confirmed by altering
pH, ionic strength, temperature, and time. Moreover, we proposed a probable
mechanism of fluorochromic phenomenon, in connection with the aromatic ring
structure of polyoxyethylene ether substituent in CrEL. Based on our findings, we
concluded that this new fluorescent microemulsion is a promising drug carrier
that can facilitate active drug detection with a label-free strategy. Although
further research is required to understand the exact mechanism behind its
fluorescence property, this work provided valuable guidance to develop new
biosensors based on fluorescent microemulsion.
PMID- 28703571
TI - Facile Fabrication of Ultra-Stretchable Metallic Nanocluster Films for Wearable
Electronics.
AB - With recent progress in flexible electronics, developing facile one-step
techniques for fabricating stretchable conductors and interconnects remain
essential. It is also desirable for these processes to have a small number of
processing steps, incorporate micropatterning, and be capable of being
effortlessly implemented for manufacturing of wearable logic circuits. A low
vacuum flash evaporation of Au nanoclusters is proposed as a facile method to
fabricate highly stretchable conductors capable of fulfilling all such
requirements. High metal-elastomer adhesion on textured substrates ensures low
surface resistances (100% strain ~ 25 Omega-sq-1) where thin film Au accommodate
strain like a "bellow". Stretchability for conductors deposited on non
prestretched textured substrates up to 150% and smooth PDMS substrates up to 200%
are shown. The system is modeled on a microscopic system calculating 2-D current
continuity equations. Devising low cost techniques for fabricating stretchable
conductors remains essential and in that direction stretchable circuits, heating
elements have been demonstrated.
PMID- 28703572
TI - Development of Epigallocatechin-3-gallate-Encapsulated
Nanohydroxyapatite/Mesoporous Silica for Therapeutic Management of Dentin
Surface.
AB - In dental clinic, unsatisfactory management of the dentin surface after dentin
exposure often leads to the occurrence of dentin hypersensitivity and caries.
Current approaches can occlude the tubules on the dentin surface to relieve
dentin hypersensitivity; however, the blocked tubules are generally weak in
combating daily tooth erosion and abrasion. Moreover, cariogenic bacteria, such
as Streptococcus mutans, produce biofilm on the dentin surface, causing caries
and compromising the tubules' sealing efficacy. To overcome this problem, the
present study focused on establishing a versatile biomaterial, epigallocatechin-3
gallate-encapsulated nanohydroxyapatite/mesoporous silica nanoparticle
(EGCG@nHAp@MSN), for therapeutic management of the dentin surface. The
effectiveness of the biomaterial on dentinal tubule occlusion, including
resistances against acid and abrasion, was evaluated by field-emission scanning
electron microscopy (FESEM) and dentin permeability measurement. The inhibitory
capability of the biomaterial on S. mutans biofilm formation was investigated by
confocal laser scanning microscopy (CLSM), 3-(4,5-dimethylthiazol-2-yl)-2,5
diphenyltetrazolium bromide (MTT) assay, colony forming units (CFU) counts, and
FESEM. Results demonstrated for the first time that the use of EGCG@nHAp@MSN on
the dentin surface was capable of effectively occluding dentinal tubules,
reducing dentin permeability, and achieving favorable acid- and abrasion
resistant stability. Furthermore, EGCG@nHAp@MSN held the capability to
continuously release EGCG, Ca, and P, and significantly inhibit the formation and
growth of S. mutans biofilm on the dentin surface. Thus, the development of
EGCG@nHAp@MSN bridges the gap between multifunctional concept and dental clinical
practice and is promising in providing dentists a therapeutic strategy for the
management of the dentin surface to counter dentin hypersensitivity and caries.
PMID- 28703573
TI - Recyclable Trifluoromethylation Reagents from Fluoroform.
AB - We present a strategy to rationally prepare CF3- transfer reagents at ambient
temperature from HCF3. We demonstrate that a highly reactive CF3- adduct can be
synthesized from alkali metal hydride, HCF3, and borazine Lewis acids in
quantitative yield at room temperature. These nucleophilic reagents transfer CF3-
to substrates without additional chemical activation, and after CF3 transfer, the
free borazine is quantitatively regenerated. These features enable syntheses of
popular nucleophilic, radical, and electrophilic trifluoromethylation reagents
with complete recycling of the borazine Lewis acid.
PMID- 28703574
TI - Influence of the Cation Adducts in the Analysis of Matrix-Assisted Laser
Desorption Ionization Imaging Mass Spectrometry Data from Injury Models of Rat
Spinal Cord.
AB - Imaging mass spectrometry (IMS) is quickly becoming a technique of reference to
visualize the lipid distribution in tissue sections. Still, many questions remain
open, and data analysis has to be optimized to avoid interpretation pitfalls.
Here we analyze how the variation on the [Na+]/[K+] relative abundance affects
the detection of lipids between sections of spinal cord of (uninjured) control
rats and of models of spinal cord demyelination and traumatic contusion injury.
The [M + Na]+/[M + K]+ adducts ratio remained approximately constant along
transversal and longitudinal sections of spinal cord from control animals, but it
strongly changed depending on the type of lesion. A substantial increase in the
abundance of [M + Na]+ adducts was observed in samples from spinal cord with
demyelination, while the intensity of the [M + K]+ adducts was stronger in those
sections from mechanically injured spinal cords. Such changes masked the
modifications in the lipid profile due to the injury and only after summing the
signal intensity of all adducts and corresponding monoprotonated molecular ions
of each detected lipid in a single variable, it was possible to unveil the real
changes in the lipid profile due to the lesion. Such lipids included
glycerophospholipids (both diacyl and aryl-acyl), sphingolipids, and nonpolar
lipids (diacyl and triacylglycerols), which are the main lipid classes detected
in positive-ion mode. Furthermore, the results demonstrate the sensitivity of the
technique toward modification in tissue homeostasis and that the [M + Na]+/[M +
K]+ ratio may be used to detect alterations in such homeostasis.
PMID- 28703575
TI - A Novel Family of Small Molecules that Enhance the Intracellular Delivery and
Pharmacological Effectiveness of Antisense and Splice Switching Oligonucleotides.
AB - The pharmacological effectiveness of oligonucleotides has been hampered by their
tendency to remain entrapped in endosomes, thus limiting their access to
cytosolic or nuclear targets. We have previously reported a group of small
molecules that enhance the effects of oligonucleotides by causing their release
from endosomes. Here, we describe a second novel family of oligonucleotide
enhancing compounds (OECs) that is chemically distinct from the compounds
reported previously. We demonstrate that these molecules substantially augment
the actions of splice switching oligonucleotides (SSOs) and antisense
oligonucleotides (ASOs) in cell culture. We also find enhancement of SSO effects
in a murine model. These new compounds act by increasing endosome permeability
and causing partial release of entrapped oligonucleotides. While they also affect
the permeability of lysosomes, they are clearly different from typical
lysosomotropic agents. Current members of this compound family display a
relatively narrow window between effective dose and toxic dose. Thus, further
improvements are necessary before these agents can become suitable for
therapeutic use.
PMID- 28703576
TI - Tc(VII) and Cr(VI) Interaction with Naturally Reduced Ferruginous Smectite from a
Redox Transition Zone.
AB - Fe(II)-rich clay minerals found in subsurface redox transition zones (RTZs) can
serve as important sources of electron equivalents limiting the transport of
redox-active contaminants. While most laboratory reactivity studies are based on
reduced model clays, the reactivity of naturally reduced field samples remains
poorly explored. Characterization of the clay size fraction of a fine-grained
unit from the RTZ interface at the Hanford site, Washington, including
mineralogy, crystal chemistry, and Fe(II)/(III) content, indicates that
ferruginous montmorillonite is the dominant mineralogical component. Oxic and
anoxic fractions differ significantly in Fe(II) natural content, but FeTOTAL
remains constant, demonstrating no Fe loss during its reduction-oxidation
cyclings. At native pH of 8.6, the anoxic fraction, despite its significant
Fe(II), ~23% of FeTOTAL, exhibits minimal reactivity with TcO4- and CrO42- and
much slower reaction kinetics than those measured in studies with
biologically/chemically reduced model clays. Reduction capacity is enhanced by
added/sorbed Fe(II) (if Fe(II)SORBED > 8% clay Fe(II)LABILE); however, the
kinetics of this conceptually surface-mediated reaction remain sluggish. Surface
sensitive Fe L-edge X-ray absorption spectroscopy shows that Fe(II)SORBED and the
resulting reducing equivalents are not available in the outermost few nanometers
of clay surfaces. Slow kinetics thus appear related to diffusion-limited access
to electron equivalents retained within the clay mineral structure.
PMID- 28703577
TI - Structural Investigation of Chemiresistive Sensing Mechanism in Redox-Active
Porous Coordination Network.
AB - By changing the rate of evaporation, two kinds of crystalline films composed of
redox-active porous coordination networks (1 and 2) were selectively prepared on
a gold-patterned substrate using a DMF solution of 2,5,8-tri(4-pyridyl)1,3
diazaphenalene and Cd(NO3)2. We found the highly sensitive humidity sensing
ability of film 1. Single crystal structures and infrared spectroscopic analyses
before and after hydration of a single crystal of 1 revealed the sensing
mechanism: exchange of nitrate ions with water on Cd atoms occurred in hydrated
conditions to generate a conductive cationic network.
PMID- 28703578
TI - Detection of a Subset of Posttranscriptional Transfer RNA Modifications in Vivo
with a Restriction Fragment Length Polymorphism-Based Method.
AB - Transfer RNAs (tRNAs) are among the most heavily modified RNA species.
Posttranscriptional tRNA modifications (ptRMs) play fundamental roles in
modulating tRNA structure and function and are being increasingly linked to human
physiology and disease. Detection of ptRMs is often challenging, expensive, and
laborious. Restriction fragment length polymorphism (RFLP) analyses study the
patterns of DNA cleavage after restriction enzyme treatment and have been used
for the qualitative detection of modified bases on mRNAs. It is known that some
ptRMs induce specific and reproducible base "mutations" when tRNAs are reverse
transcribed. For example, inosine, which derives from the deamination of
adenosine, is detected as a guanosine when an inosine-containing tRNA is reverse
transcribed, amplified via polymerase chain reaction (PCR), and sequenced. ptRM
dependent base changes on reverse transcription PCR amplicons generated as a
consequence of the reverse transcription reaction might create or abolish
endonuclease restriction sites. The suitability of RFLP for the detection and/or
quantification of ptRMs has not been studied thus far. Here we show that
different ptRMs can be detected at specific sites of different tRNA types by
RFLP. For the examples studied, we show that this approach can reliably estimate
the modification status of the sample, a feature that can be useful in the study
of the regulatory role of tRNA modifications in gene expression.
PMID- 28703579
TI - Mechanism and Scope of Phosphinidene Transfer from Dibenzo-7-phosphanorbornadiene
Compounds.
AB - Dibenzo-7-phosphanorbornadiene compounds, RPA (A = C14H10 or anthracene), are
investigated as phosphinidene sources upon thermally induced (70-90 degrees C)
anthracene elimination. Analysis of substituent effects reveals that pi-donating
dialkylamide groups are paramount to successful phosphinidene transfer; poorer pi
donors give reduced or no transfer. Substituent steric bulk is also implicated in
successful transfer. Molecular beam mass spectrometry (MBMS) studies of each
derivative reveal dialkylamide derivatives to be promising precursors for further
gas-phase spectroscopic studies of phosphinidenes; in particular, we present
evidence of direct detection of the dimethylamide derivative, [Me2N?P]. Kinetic
investigations of iPr2NPA thermolysis in 1,3-cyclohexadiene and/or benzene-d6 are
consistent with a model of unimolecular fragmentation to yield free phosphinidene
[iPr2N?P] as a transient reactive intermediate. This conclusion is probed by
density functional theory (DFT) calculations, which favored a mechanistic model
featuring free singlet aminophosphinidenes. The breadth of phosphinidene
acceptors is expanded to unsaturated substrates beyond 1,3-dienes to include
olefins and alkynes; this provides a new synthetic route to valuable amino
substituted phosphiranes and phosphirenes, respectively. Stereoselective
phosphinidene transfer to olefins is consistent with singlet phosphinidene
reactivity by analogy with the Skell hypothesis for singlet carbene addition to
olefins.
PMID- 28703580
TI - Complex Permittivity of Ionic Liquid Mixtures Investigated by Terahertz Time
Domain Spectroscopy.
AB - Ionic liquids are salts found in their liquid state at ambient temperature. The
physicochemical properties of ionic liquids can be tailored by selecting
constituent cation and anion from numerous available ions. The physicochemical
properties can be further tuned by mixing different neat ionic liquids. Reported
data of ionic liquid mixtures reveal that frequently investigated properties such
as density, viscosity, and thermal stability follow corresponding mixing laws.
Complex permittivity in the interval of terahertz frequencies is of great
importance to understand the molecular interactions and the solvation dynamics
which drive the macroscopic properties of ionic liquids; however, to the best of
our knowledge, there are few reports about the mixing behavior of complex
permittivity in ionic liquid mixtures. In this contribution, binary mixtures of 1
butyl-3-methylimidazoulium iodide ([C4C1im]I) and 1-butyl-3- methylimidazoulium
bis(trifluoromethylsulfonyl)imide ([C4C1im][NTf2]) are investigated in the
terahertz spectral range, and the resulting low-energy spectra are analyzed in
order to clarify the mixing laws at play. The results show that the complex
permittivity of mixtures of [C4C1im]I and ([C4C1im][NTf2] obeys a linear mixing
law.
PMID- 28703581
TI - Multiple Mechanisms for the Thermal Decomposition of Metallaisoxazolin-5-ones
from Computational Investigations.
AB - The thermal decompositions of metallaisoxazolin-5-ones containing Ir, Rh, or Co
are investigated using density functional theory. The experimentally observed
decarboxylations of these molecules are found to proceed through retro-(3+2)
cycloaddition reactions, generating the experimentally reported eta2 side-bonded
nitrile complexes. These intermediates can isomerize in situ to yield a eta1
nitrile complex. A competitive alternative pathway is also found where the
decarboxylation happens concertedly with an aryl migration process, producing a
eta1 isonitrile complex. Despite their comparable stability, these eta1 bonded
species were not detected experimentally. The experimentally detected eta2 side
bound species are likely involved in the subsequent C-H activation reactions with
hydrocarbon solvents reported for some of these metallaisoxazolin-5-ones.
PMID- 28703582
TI - Organocatalytic Asymmetric Mannich/Aza-Michael Cascade Reaction of delta-Formyl
alpha,beta-unsaturated Ketones with Cyclic N-Sulfimines: Enantioselective
Synthesis of Benzosulfamidate-Fused Pyrrolidines.
AB - A catalytic highly enantioselective Mannich/aza-Michael cascade reaction of delta
formyl-alpha,beta-unsaturated ketones with cyclic N-sulfimines, promoted by
diphenylprolinol TMS ether as an organocatalyst, has been developed for the
synthesis of chiral benzosulfamidate-fused pyrrolidines, which generated in good
yields and with high diastero- and enantioselectivities. Further chemical
transformations have been performed with chiral benzosulfamidate-fused
pyrrolidines.
PMID- 28703583
TI - CoNSEnsX+ Webserver for the Analysis of Protein Structural Ensembles Reflecting
Experimentally Determined Internal Dynamics.
AB - Ensemble-based models of protein structure and dynamics reflecting experimental
parameters are increasingly used to obtain deeper understanding of the role of
dynamics in protein function. Such ensembles differ substantially from those
routinely deposited in the PDB and, consequently, require specialized validation
and analysis methodology. Here we describe our completely rewritten online
validation tool, CoNSEnsX+, that offers a standardized way to assess the
correspondence of such ensembles to experimental NMR parameters. The server
provides a novel selection feature allowing a user-selectable set and weights of
different parameters to be considered. This also offers an approximation of
potential overfitting, namely, whether the number of conformers necessary to
reflect experimental parameters can be reduced in the ensemble provided. The
CoNSEnsX+ webserver is available at consensx.itk.ppke.hu . The corresponding
Python source code is freely available on GitHub ( github.com/PPKE
Bioinf/consensx.itk.ppke.hu ).
PMID- 28703584
TI - Synthesis of 2-Amino-3-hydroxy-3H-indoles via Palladium-Catalyzed One-Pot
Reaction of Isonitriles, Oxygen, and N-Tosylhydrazones Derived from 2
Acylanilines.
AB - A cyanide-free one-pot procedure was developed to access 2-amino-3-hydroxy-3H
indoles, which involved: (1) in situ formation of ketenimines by the reaction of
N'-(1-(2-aminophenyl)ethylidene)-p-tosylhydrazones with isonitriles; (2) the
intramolecular nucleophilic attack of ketenimines by the amino in phenyl
furnishing the ring closure leading to 2-aminoindoles; (3) the oxidation of 2
aminoindoles by O2 leading to 2-amino-3-hydroxy-3H-indoles. This strategy
represents not only a key compliment to the sporadic synthetic methods toward 2
amino-3-hydroxy-3H-indoles but also progress in N-tosylhydrazone, isonitrile, and
ketenimine chemistry.
PMID- 28703585
TI - Tunable Chiral Second-Order Nonlinear Optical Chromophores Based on Helquat
Dications.
AB - Fourteen new dipolar cations have been synthesized, containing methoxy or
tertiary amino electron donor groups attached to helquat (Hq) acceptors. These Hq
derivatives have been characterized as their TfO- salts by using various
techniques including NMR and electronic absorption spectroscopies. UV-vis spectra
show intense, relatively low energy absorptions with lambdamax ~ 400-600 nm,
attributable to intramolecular charge-transfer (ICT) excitations. Single-crystal
X-ray structures have been solved for two of the chromophores, one as its PF6-
salt, revealing centrosymmetric packing arrangements (space groups Pbca and P1).
Molecular quadratic nonlinear optical (NLO) responses have been determined
directly by using hyper-Rayleigh scattering (HRS) with a 800 nm laser, and
indirectly via Stark (electroabsorption) spectroscopy for the low energy
absorption bands. The obtained static first hyperpolarizabilities beta0 range
from moderate to large: (9-140) * 10-30 esu from HRS in MeCN and (44-580) * 10-30
esu from the Stark data in PrCN. The magnitude of beta0 increases upon either
extending the pi-conjugation length or replacing a methoxy with a tertiary amino
electron donor substituent. Density functional theory (DFT) and time-dependent
DFT calculations on selected tertiary amino chromophores confirm that the low
energy absorptions have ICT character. Relatively good agreement between the
simulated and experimental UV-vis absorption spectra is achieved by using the CAM
B3LYP functional with the 6-311G(d) basis set. The betatot values predicted by
using DFT at the same level of theory are large ((472-1443) * 10-30 esu in MeCN).
Both the theoretical and experimental results show that para-conjugation between
Hq and electron donor fragments is optimal, and enlarging the Hq unit is
inconsequential with respect to the molecular quadratic NLO response.
PMID- 28703586
TI - Effect of Bidispersity on Structure and Entanglement of Confined Polymer Films.
AB - Using Monte Carlo simulations combined with a geometric primitive path analysis
method (Z1 algorithm), we investigate the effect of bidispersity on the structure
and entanglement of polymer films which consist of short (the molecular length is
below the characteristic entanglement molecular length) and long (the molecular
length is above the characteristic entanglement molecular length) chains between
two neutral walls. Our results demonstrate the length-based migrations of chains
in bidisperse films (the longer chains reside away from the walls and the shorter
chains are close to the walls), which becomes more obvious with the decrease in
the weight fraction of long chains. With decreasing the weight fraction of long
chains, the number of short-long entanglements exhibits a dramatic increase,
whereas the number of long-long entanglements exhibits a slight decrease, which
indicates that short chains can significantly affect the local situations of
entanglements of bidisperse polymer films. On the basis of the constraint release
mechanism, our simulations imply that for the lower weight fraction of long
chains, the local degree of confinement instead of the long-long entanglements
has a marked effect on the relaxation of long chains, due to the fast relaxation
of short chains dilating the tube diameter of long chains. However, for the
higher weight fraction of long chains, after the relaxation of short chains, the
long-long entanglements are in sufficient quantities to restrict long chains
within a tube, which implies that the relaxation of long chains is hardly
affected by the number of short-long entanglements. Our work can be helpful for
understanding the microscopic structure and entanglement of bidisperse polymer
films, which can provide computational support for their various technological
applications.
PMID- 28703587
TI - Ionization and Conformational Equilibria of Citric Acid: Delocalized Proton
Binding in Solution.
AB - The microspeciation of citric acid is studied by analyzing NMR titration data.
When the site binding (SB) model, which assumes fully localized proton binding to
the carboxylic groups, is used to obtain microscopic energy parameters
(dissociation constants, pair and triplet interaction energies between charged
carboxylate groups), contradictory results are obtained. The resulting
macroscopic constants are in very good agreement with the values reported in the
literature using potentiometry. However, the found pair interaction energy
between the terminal carboxylates and the triplet interaction energy are
physically meaningless. To solve this apparent contradiction, we consider the
possibility of delocalized proton binding, so that the proton can be exchanged at
high velocity in the NMR time scale through short, strong, low-barrier (SSLB)
hydrogen bonds. With this aim, ab initio MP2 calculations using the SMD
polarizable continuum model for the solvent were performed and the fully roto
microspeciation elucidated. First, fully localized proton binding was assumed,
and the resulting microstate probabilities are in reasonable agreement with those
reported in previous works that use selective blocking of the carboxylic groups.
They are, however, in clear disagreement with the microstate probabilities
derived from the NMR titration data, which predict, within a very narrow
confidence interval, a unique microspecies for the symmetric di-ionized form.
Moreover, counterintuitively, the interaction between terminal charged groups is
much larger than that between central and terminal groups. As a consequence, we
have explored the possibility of delocalized proton binding by calculating the
energy of intermediate proton positions between two carbolxylic groups. The
results reveal that the exchange of the proton through the hydrogen bonds is in
some cases produced without energetic barrier. This effect is specially relevant
in the di-ionized form, with all the most stable conformations forming a SSLB,
which together would constitute the only microstate detected by NMR. An
alternative reaction scheme for the ionization process, based on proton
delocalization, is proposed.
PMID- 28703588
TI - Nonenzymatic beta-Carotene Degradation in Provitamin A-Biofortified Crop Plants.
AB - Provitamin A biofortification, the provision of provitamin A carotenoids through
agriculture, is regarded as an effective and sustainable intervention to defeat
vitamin A deficiency, representing a global health problem. This food-based
intervention has been questioned in conjunction with negative outcomes for
smokers and asbestos-exposed populations of the CARET and ATBC trials in which
very high doses of beta-carotene were supplemented. The current notion that beta
carotene cleavage products (apocarotenoids) represented the harmful agents is the
basis of the here-presented research. We quantitatively analyzed numerous plant
food items and concluded that neither the amounts of apocarotenoids nor beta
carotene provided by plant tissues, be they conventional or provitamin A
biofortified, pose an increased risk. We also investigated beta-carotene
degradation pathways over time. This reveals a substantial nonenzymatic
proportion of carotene decay and corroborates the quantitative relevance of
highly oxidized beta-carotene polymers that form in all plant tissues
investigated.
PMID- 28703589
TI - Metabolic Pathways Regulated by Chitosan Contributing to Drought Resistance in
White Clover.
AB - Increased endogenous chitosan (CTS) could be associated with improved drought
resistance in white clover (Trifolium repens). Plants were pretreated with or
without 1 mg/mL CTS and then were subjected to optimal or water-limited condition
in controlled growth chambers for 6 days. Phenotypic and physiological results
indicated that exogenous CTS significantly improved drought resistance of white
clover. Metabolome results showed that exogenous CTS induced a significant
increase in endogenous CTS content during dehydration accompanied by the
maintenance of greater accumulation of sugars, sugar alcohols, amino acids,
organic acids, and other metabolites (ascorbate, glutathione, flavonoids,
putrescine, and spermidine). These compounds are associated with osmotic
adjustment, antioxidant defense, stress signaling, and energy metabolism under
stress condition. Similarly, transcriptome revealed that many genes in relation
to amino acid and carbohydrate metabolism, energy production and conversion, and
ascorbate-glutathione and flavonoid metabolism were significantly up-regulated by
CTS in response to dehydration stress. CTS-induced drought resistance was
associated with the accumulation of stress protective metabolites, the
enhancement of ascorbate-glutathione and tricarboxylic acid cycle, and increases
in the gamma-aminobutyric acid shunt, polyamine synthesis, and flavonoids
metabolism contributing to improved osmotic adjustment, antioxidant capacity,
stress signaling, and energy production for stress defense, thereby maintaining
metabolic homeostasis under dehydration stress.
PMID- 28703590
TI - Photothermal, Targeting, Theranostic Near-Infrared Nanoagent with SN38 against
Colorectal Cancer for Chemothermal Therapy.
AB - Cancer research regarding near-infrared (NIR) agents for chemothermal therapy
(CTT) has shown that agents with specific functions are able to inhibit tumor
growth. The aim of current study was to optimize CTT efficacy for treatment of
colorectal cancer (CRC) by exploring strategies which can localize high
temperature within tumors and maximize chemotherapeutic drug uptake. We designed
a new and simple multifunctional NIR nanoagent composed of the NIR cyanine dye,
polyethylene glycol, and a cyclic arginine-glycine-aspartic acid peptide and
loaded with the anti-CRC chemotherapeutic agent, 7-ethyl-10-hydroxy-camptothecin
(SN38). Each component of this nanoagent exhibited its specific functions that
help boost CTT efficacy. The results showed that this nanoagent greatly
strengthens the theranostic effect of SN38 and CTT against CRC due to its NIR
imaging ability, photothermal, enhanced permeability and retention (EPR) effect,
reticuloendothelial system avoidance, and angiogenic blood vessel-targeting
properties. This NIR nanoagent will help facilitate development of new strategies
for treating CRC.
PMID- 28703591
TI - Time-Resolved Linear Dichroism Measurements of Carbonmonoxy Myoglobin as a Probe
of the Microviscosity in Crowded Environments.
AB - The distribution of viscosities in living cells is heterogeneous because of the
different sizes and natures of macromolecular components. When thinking about
protein folding/function processes in such an environment, the relevant
(micro)viscosity at the micrometer length scale is necessarily distinguished from
the bulk (macro)viscosity. The concentration dependencies of microviscosities are
determined by a number of factors, such as electrostatic interactions, van der
Waals forces, and excluded volume effects. To explore such factors, the
rotational diffusion time of myoglobin in the presence of varying concentrations
of macromolecules that differ in molecular weight (dextran 6000, 10 000, and 70
000), shape (dextran versus Ficoll), size, and surface charge is measured with
time-resolved linear dichroism spectroscopy. The results of these studies offer
simple empirically determined linear and exponential functions useful for
predicting microviscosities as a function of concentration for these
macromolecular crowders that are typically used to study crowding effects on
protein folding. To understand how relevant these microviscosity measurements are
to intracellular environments, the TRLD results are discussed in the context of
studies that measure viscosity in cells.
PMID- 28703592
TI - Interactions between beta2-Adrenoceptor Ligands and Membrane: Atomic-Level
Insights from Magic-Angle Spinning NMR.
AB - To understand the relationship between structural properties of the beta2
adrenoceptor ligands and their interactions with membranes, we have investigated
the location and distribution of five beta2 agonists with distinct clinical
durations and onsets of action (indacaterol, two indacaterol analogues,
salmeterol and formoterol) in monounsaturated model membranes using magic angle
spinning NMR to measure these interactions through both 1H nuclear Overhauser
enhancement (NOE) and paramagnetic relaxation enhancement (PRE) techniques. The
hydrophilic aromatic groups of all five beta2 agonists show maximum distribution
in the lipid/water interface, but distinct location and dynamic behavior were
observed for the lipophilic aromatic rings. Our study elucidates at atomic level
that the hydrophobicity and substitution geometry of lipophilic groups play
important roles in compound-lipid interactions.
PMID- 28703593
TI - A Coarse-Grained Model for Free and Template-Bound Porphyrin Nanorings.
AB - Coarse-grained simulation models are developed to study both template-bound and
free porphyrin nanoring systems. Key interactions are modeled with relatively
simple (and physically motivated) energy functions which allow for relatively
facile transfer both between different ring sizes and between the template-bound
and free nanoring systems. The effects of varying the model parameters on the
respective radii of gyration are determined. The effects of including different
templates on the ring structure are investigated both in terms of the detailed
geometry of the template and the interaction strength between the template and
the metal centers in the nanorings. The role of the template-nanoring interaction
strength in controlling potential "caterpillar track" rotational motion is
discussed. The relationship of the model to experimental small-angle X-ray,
exchange spectroscopy, and electron spin resonance results is discussed.
PMID- 28703594
TI - Preparation of Curcumin-Piperazine Coamorphous Phase and Fluorescence
Spectroscopic and Density Functional Theory Simulation Studies on the Interaction
with Bovine Serum Albumin.
AB - In the present study, a new coamorphous phase (CAP) of bioactive herbal
ingredient curcumin (CUR) with high solubilitythe was screened with
pharmaceutically acceptable coformers. Besides, to provide basic information for
the best practice of physiological and pharmaceutical preparations of CUR-based
CAP, the interaction between CUR-based CAP and bovine serum albumin (BSA) was
studied at the molecular level in this paper. CAP of CUR and piperazine with
molar ratio of 1:2 was prepared by EtOH-assisted grinding. The as-prepared CAP
was characterized by powder X-ray diffraction, modulated temperature differential
scanning calorimetry, thermogravimetric analysis, Fourier-transform infrared, and
solid-state 13C nuclear magnetic resonance. The 1:2 CAP stoichioimetry was
sustained by C?O...H hydrogen bonds between the N-H group of the piperazine and
the C?O group of CUR; piperazine stabilized the diketo structure of CUR in CAP.
The dissolution rate of CUR-piperazine CAP in 30% ethanol-water was faster than
that of CUR; the t50 values were 243.1 min for CUR and 4.378 min for CAP.
Furthermore, interactions of CUR and CUR-piperazine CAP with BSA were
investigated by fluorescence spectroscopy and density functional theory (DFT)
calculation. The binding constants (Kb) of CUR and CUR-piperazine CAP with BSA
were 10.0 and 9.1 * 103 L mol-1 at 298 K, respectively. Moreover, DFT simulation
indicated that the interaction energy values of hydrogen-bonded interaction in
the tryptophan-CUR and tryptophan-CUR-piperazine complex were -26.1 and -17.9 kJ
mol-1, respectively. In a conclusion, after formation of CUR-piperazine CAP, the
interaction forces between CUR and BSA became weaker.
PMID- 28703595
TI - Quorum-Quenching Human Designer Cells for Closed-Loop Control of Pseudomonas
aeruginosa Biofilms.
AB - Current antibiotics gradually lose their efficacy against chronic Pseudomonas
aeruginosa infections due to development of increased resistance mediated by
biofilm formation, as well as the large arsenal of microbial virulence factors
that are coordinated by the cell density-dependent phenomenon of quorum sensing.
Here, we address this issue by using synthetic biology principles to rationally
engineer quorum-quencher cells with closed-loop control to autonomously dampen
virulence and interfere with biofilm integrity. Pathogen-derived signals
dynamically activate a synthetic mammalian autoinducer sensor driving downstream
expression of next-generation anti-infectives. Engineered cells were able to
sensitively score autoinducer levels from P. aeruginosa clinical isolates and
mount a 2-fold defense consisting of an autoinducer-inactivating enzyme to
silence bacterial quorum sensing and a bipartite antibiofilm effector to dissolve
the biofilm matrix. The self-guided cellular device fully cleared autoinducers,
potentiated bacterial antibiotic susceptibility, substantially reduced biofilms,
and alleviated cytotoxicity to lung epithelial cells. We believe this strategy of
dividing otherwise coordinated pathogens and breaking up their shielded
stronghold represents a blueprint for cellular anti-infectives in the
postantibiotic era.
PMID- 28703596
TI - Rhodomollanol A, a Highly Oxygenated Diterpenoid with a 5/7/5/5 Tetracyclic
Carbon Skeleton from the Leaves of Rhododendron molle.
AB - A novel diterpenoid with an unprecedented carbon skeleton, rhodomollanol A (1),
and a new grayanane diterpenoid, rhodomollein XXXI (2), were isolated from the
leaves of Rhododendron molle. Their structures were elucidated using
comprehensive spectroscopic methods and single-crystal X-ray diffraction.
Compound 1 possesses a unique cis/trans/trans/cis/cis-fused 3/5/7/5/5/5
hexacyclic ring system featuring a rare 7-oxabicyclo[4.2.1]nonane core decorated
with three cyclopentane units. The plausible biosynthetic pathway for 1 was
proposed. Compound 1 exhibited moderate PTP1B inhibitory activity.
PMID- 28703597
TI - Natural and Semisynthetic Tigliane Diterpenoids with New Carbon Skeletons from
Euphorbia dracunculoides as a Wnt Signaling Pathway Inhibitor.
AB - Euphordraculoates A (1) and B (2), featuring tigliane diterpenoids with two new
carbon skeletons, were characterized as metabolites of Euphorbia dracunculoides
and semisynthetic products, respectively. Their structures were determined by
spectroscopic analyses and X-ray crystallography. The respective biosynthetic and
chemical formation mechanisms for 1 and 2 from a known tigliane 3 was proposed.
The detailed decarbonization mechanism from 3 to 2 was further explored by 18O
labeling experiment. Compound 2 could inhibit Wnt pathway in a dose- and time
dependent manner.
PMID- 28703598
TI - Synthesis of Dibenzo[h,rst]pentaphenes and Dibenzo[fg,qr]pentacenes by the
Chemoselective C-O Arylation of Dimethoxyanthraquinones.
AB - A convenient method for the syntheses of dibenzo[h,rst]pentaphenes and
dibenzo[fg,qr]pentacenes via the ruthenium-catalyzed chemoselective C-O arylation
of 1,4- and 1,5-dimethoxyanthraquinones is described. Dimethoxyanthraquinones
reacted selectively with arylboronates at the ortho C-O bonds to give diarylation
products. An efficient two-step procedure consisting of a Corey-Chaykofsky
reaction and subsequent dehydrative aromatization afforded derivatives of
dibenzo[h,rst]pentaphenes and dibenzo[fg,qr]pentacenes. Hole-transporting
characteristics were observed for a device with a bottom-contact configuration
that was fabricated from one of these polycyclic aromatic hydrocarbons.
PMID- 28703599
TI - Mechanistic Pathways in Amide Activation: Flexible Synthesis of Oxazoles and
Imidazoles.
AB - The preparation of substituted aminooxazoles and aminoimidazoles from alpha
arylamides and alpha-aminoamides through triflic anhydride-mediated amide
activation is reported. These reactions proceed via the intermediacy of nitrilium
adducts and feature N-oxide-promoted umpolung of the alpha-position of amides as
well as a mechanistically intriguing sequence that results in sulfonyl migration
from nitrogen to carbon. Quantum-chemical mechanistic analysis sheds light on the
intricacies of the process.
PMID- 28703600
TI - Multireference Electronic Structures of Fe-Pyridine(diimine) Complexes over
Multiple Oxidation States.
AB - Noninnocent (redox-active) ligands are increasingly exploited in the design of
coordination compounds of earth-abundant transition metals having interesting
reactive and catalytic activities. Particular examples of such ligands include
those in the pyridine(diimine) (also referred to as bis(imino)pyridine) family.
The electronic structures of these compounds are characterized by significant
complexity, such that routine single-reference methodologies, for example, Kohn
Sham density functional theory, may be challenged to describe them physically,
that is, with quantitatively accurate descriptions of geometries, charge
distributions, and spin-state energy separations. We report here RASSCF/RASPT2
calculations on iron pyridine(diimine) complexes over three formal oxidation
states that illustrate the highly multiconfigurational characters of these
compounds in general and that also offer insights into their electronic ground
states and charge distributions.
PMID- 28703601
TI - Enantioselective [3 + 2] Annulation of Enals with 2-Aminoacrylates Catalyzed by N
Heterocyclic Carbene.
AB - A novel and convenient strategy for the enantioselective synthesis of gamma
lactam derivatives via N-heterocyclic carbene catalyzed formal [3 + 2] annulation
of enals with 2-aminoacrylates is disclosed. This activation mode provides a
complementary approach to the synthesis of various gamma-lactam derivatives in
good yields with excellent diastereo- and enantioselectivities. In this process,
two consecutive stereocenters are constructed, and a quaternary carbon center is
also established.
PMID- 28703602
TI - The Psychological Health Benefits of Accepting Negative Emotions and Thoughts:
Laboratory, Diary, and Longitudinal Evidence.
AB - Individuals differ in the degree to which they tend to habitually accept their
emotions and thoughts without judging them-a process here referred to as habitual
acceptance. Acceptance has been linked with greater psychological health, which
we propose may be due to the role acceptance plays in negative emotional
responses to stressors: acceptance helps keep individuals from reacting to-and
thus exacerbating-their negative mental experiences. Over time, experiencing
lower negative emotion should promote psychological health. To test these
hypotheses, Study 1 (N = 1,003) verified that habitually accepting mental
experiences broadly predicted psychological health (psychological well-being,
life satisfaction, and depressive and anxiety symptoms), even when controlling
for potentially related constructs (reappraisal, rumination, and other
mindfulness facets including observing, describing, acting with awareness, and
nonreactivity). Next, in a laboratory study (Study 2, N = 156), habitual
acceptance predicted lower negative (but not positive) emotional responses to a
standardized stressor. Finally, in a longitudinal design (Study 3, N = 222),
acceptance predicted lower negative (but not positive) emotion experienced during
daily stressors that, in turn, accounted for the link between acceptance and
psychological health 6 months later. This link between acceptance and
psychological health was unique to accepting mental experiences and was not
observed for accepting situations. Additionally, we ruled out potential
confounding effects of gender, ethnicity, socioeconomic status, and life stress
severity. Overall, these results suggest that individuals who accept rather than
judge their mental experiences may attain better psychological health, in part
because acceptance helps them experience less negative emotion in response to
stressors. (PsycINFO Database Record
PMID- 28703603
TI - Decomposing the cross-sex misprediction bias of dating behaviors: Do men
overestimate or women underreport their sexual intentions?
AB - Men typically predict women's sexual intentions to be higher than women say they
are (Haselton & Buss, 2000). It is debated whether this cross-sex bias is because
of men overestimating women's intentions (Murray et al., 2017), women
underreporting their own intentions (Perilloux & Kurzban, 2015, 2017), or both.
To unify the current debate, we decompose the part of the bias attributable to
women underreporting versus men overestimating by using a survey method
intervention to reduce underreporting of sensitive information: eliciting
estimates about others before sensitive self-reports. First, we calibrate the
current measurement instrument to assess the overall size of the misprediction
bias (Study 1). Then, we manipulate the order-of-elicitation of self- and other
reports (Studies 2 and 3): Women report significantly higher own sexual
intentions when they are asked about other targets' intentions before their own,
suggesting that 48 to 69% of the overestimation bias is attributable to women
underreporting their own sexual intentions. Analogous analyses for the
misprediction bias about men suggest that women's overestimation bias of men's
sexual intentions is entirely because of men underreporting their own sexual
intentions. The findings have important implications for the current debate in
the literature on cross-sex misprediction biases and the literature on asking
sensitive survey questions. (PsycINFO Database Record
PMID- 28703604
TI - Dispositional, demographic, and social predictors of trajectories of intimate
partner aggression in early adulthood.
AB - OBJECTIVE: From a developmental systems perspective, the origins of maladjusted
behavior are multifaceted, interdependent, and may differ at different points in
development. Personality traits influence developmental outcomes, as do
socialization environments, but the influence of personality depends on the
socialization environment, and the influence of the socialization environment
varies according to personality. The present study takes a developmental systems
approach to investigate pathways through which dispositional traits in childhood
might act in concert with peer and parental socialization contexts to predict
trajectories of intimate partner aggression (IPA) during emerging adulthood.
METHOD: The study included 466 participants (49% male, 81% European American, 15%
African American) from a longitudinal study of social development. Measures of
demographics, temperament, personality, parent-child relations, romantic
relationships, peer relationships, and IPA were administered between 5 and 23
years of age. The study used latent growth curve analysis to predict variations
in trajectories of IPA during early adulthood. RESULTS: Numerous variables
predicted risk for the perpetration of IPA, but different factors were associated
at the end of adolescence (e.g., psychopathic traits) than with changes across
early adulthood (e.g., friend antisociality). Males and individuals with a
history of resistance to control temperament showed enhanced susceptibility to
social risk factors, such as exposure to antisocial peers and poor parent
adolescent relations. CONCLUSIONS: Consistent with a developmental systems
perspective, multiple factors, including personality traits in early childhood
and aspects of the social environment in adolescence, predict trajectories of IPA
during early adulthood through additive, mediated, and moderated pathways.
Knowledge of these risk factors and for whom they are most influential could help
inform efforts to prevent the emergence and persistence of IPA. (PsycINFO
Database Record
PMID- 28703605
TI - Markers for context-responsiveness: Client baseline interpersonal problems
moderate the efficacy of two psychotherapies for generalized anxiety disorder.
AB - OBJECTIVE: To follow-up a randomized clinical trial that compared the acute and
long-term efficacy of 15 sessions of cognitive-behavioral therapy (CBT) versus
CBT integrated with motivational interviewing (MI) for severe generalized anxiety
disorder (GAD; Westra, Constantino, & Antony, 2016), we (a) characterized the
sample's baseline interpersonal problems, and (b) analyzed the role of several
theory-relevant problems as moderators of the comparative treatment effects on
outcome. METHOD: We first compared clients' (N = 85) baseline interpersonal
problems profile to a general clinical sample. We next conducted piecewise, 2
level growth models to analyze the interactive effects of treatment condition and
the hypothesized interpersonal problem indices of nonassertiveness (ranging from
low to high), exploitability (ranging from low to high on this specific
combination of nonassertiveness and friendliness), and overall agency (ranging
from more problems of being too submissive to more problems of being too
domineering, including friendly or hostile variants) on acute and follow-up worry
reduction. Finally, we conducted hierarchical generalized linear models to
examine these interactive effects on the likelihood of achieving clinically
meaningful worry reduction across follow-up. RESULTS: As expected, the GAD
clients evidenced more nonassertive and exploitable interpersonal problems than
the general clinical sample. Also as predicted, clients with more problematic
nonassertiveness and low overall agency in their relationships had greater follow
up worry reduction in MI-CBT versus CBT, including to a clinically significant
degree for the agency by treatment interaction. CONCLUSIONS: GAD-specific
interpersonal problems can serve as contextual markers for integrative treatment
selection and planning. (PsycINFO Database Record
PMID- 28703606
TI - Cyclical population dynamics of automatic versus controlled processing: An
evolutionary pendulum.
AB - Psychologists, neuroscientists, and economists often conceptualize decisions as
arising from processes that lie along a continuum from automatic (i.e.,
"hardwired" or overlearned, but relatively inflexible) to controlled (less
efficient and effortful, but more flexible). Control is central to human
cognition, and plays a key role in our ability to modify the world to suit our
needs. Given its advantages, reliance on controlled processing may seem
predestined to increase within the population over time. Here, we examine whether
this is so by introducing an evolutionary game theoretic model of agents that
vary in their use of automatic versus controlled processes, and in which
cognitive processing modifies the environment in which the agents interact. We
find that, under a wide range of parameters and model assumptions, cycles emerge
in which the prevalence of each type of processing in the population oscillates
between 2 extremes. Rather than inexorably increasing, the emergence of control
often creates conditions that lead to its own demise by allowing automaticity to
also flourish, thereby undermining the progress made by the initial emergence of
controlled processing. We speculate that this observation may have relevance for
understanding similar cycles across human history, and may lend insight into some
of the circumstances and challenges currently faced by our species. (PsycINFO
Database Record
PMID- 28703607
TI - None of the above: A Bayesian account of the detection of novel categories.
AB - Every time we encounter a new object, action, or event, there is some chance that
we will need to assign it to a novel category. We describe and evaluate a class
of probabilistic models that detect when an object belongs to a category that has
not previously been encountered. The models incorporate a prior distribution that
is influenced by the distribution of previous objects among categories, and we
present 2 experiments that demonstrate that people are also sensitive to this
distributional information. Two additional experiments confirm that
distributional information is combined with similarity when both sources of
information are available. We compare our approach to previous models of
unsupervised categorization and to several heuristic-based models, and find that
a hierarchical Bayesian approach provides the best account of our data. (PsycINFO
Database Record
PMID- 28703608
TI - Patient feedback as a quality improvement strategy in an acute care, inpatient
unit: An investigation of outcome and readmission rates.
AB - High psychiatric readmission rates continue while evidence suggests that care is
not perceived by patients as "patient centered." Research has focused on
aftercare strategies with little attention to the inpatient treatment itself as
an intervention to reduce readmission rates. Quality improvement strategies based
on patient-centered care may offer an alternative. We evaluated outcomes and
readmission rates using a benchmarking methodology with a naturalistic data set
from an inpatient psychiatric facility (N = 2,247) that used a quality
improvement strategy called systematic patient feedback. Benchmarks were
constructed using randomized clinical trials (RCTs) from inpatient treatment for
depression, RCTs from patient feedback in outpatient settings, and national data
on psychiatric hospital readmission rates. A systematic patient feedback system,
the Partners for Change Outcome Management System (PCOMS), was used. Overall pre
post effect sizes were d = 1.33 and d = 1.38 for patients diagnosed with a mood
disorder. These effect sizes were statistically equivalent to RCT benchmarks for
feedback and depression. Readmission rates were 6.1% (30 days), 9.5% (60 days),
and 16.4% (180 days), all lower than national benchmarks. We also found that
patients who achieved clinically significant treatment outcomes were less likely
to be readmitted. We tentatively suggest that a focus on real-time patient
outcomes as well as care that is "patient centered" may provide a path toward
lower readmission rates in addition to other evidence-based strategies after
discharge. (PsycINFO Database Record (c) 2018 APA, all rights reserved).
PMID- 28703609
TI - "Sluggish cognitive tempo in adults: Psychometric validation of the Adult
Concentration Inventory": Correction to Becker et al. (2017).
AB - Reports an error in "Sluggish Cognitive Tempo in Adults: Psychometric Validation
of the Adult Concentration Inventory" by Stephen P. Becker, G. Leonard Burns,
Annie A. Garner, Matthew A. Jarrett, Aaron M. Luebbe, Jeffery N. Epstein and Erik
G. Willcutt (Psychological Assessment, Advanced Online Publication, Apr 06, 2017,
np). In the article, the Table 1 item content was incorrectly ordered. The table,
as well as text refe/rencing Table 1 in the Results and Discussion, have been
corrected in all versions of this article. (The following abstract of the
original article appeared in record 2017-15233-001.) As interest in sluggish
cognitive tempo (SCT) increases, a primary limitation for the field is the lack
of a unified set of symptoms for assessing SCT. No existing SCT measure includes
all items identified in a recent meta-analysis as optimal for distinguishing
between SCT and attention-deficit/hyperactivity disorder (ADHD) inattention. This
study evaluates a new self-report measure for assessing SCT in adulthood, the
Adult Concentration Inventory (ACI), which was developed in response to the meta
analytic findings for assessing SCT. Using a large, multiuniversity sample (N =
3,172), we evaluated the convergent and discriminant validity and reliability of
the ACI. We also evaluated the ACI measure of SCT in relation to self-reported
demographic characteristics, daily life executive functioning, socioemotional
adjustment (i.e., anxiety/depression, loneliness, emotion dysregulation, self
esteem), and functional impairment. Exploratory confirmatory factor analyses
resulted in 10 ACI items demonstrating strong convergent and discriminant
validity from both anxiety/depressive and ADHD inattentive symptom dimensions.
SCT was moderately to-strongly correlated with daily life EF deficits, poorer
socioemotional adjustment, and greater global functional impairment. Moreover,
SCT remained uniquely associated in structural regression analyses with most of
these external criterion domains above and beyond ADHD. Finally, when
internalizing symptoms were also covaried, SCT, but not ADHD inattention,
remained significantly associated with poorer socioemotional adjustment. These
findings support the use of the ACI in future studies examining SCT in adulthood
and make a major contribution in moving the field toward a unified set of SCT
items that can be used across studies. (PsycINFO Database Record
PMID- 28703610
TI - Between- and within-person associations between negative life events and alcohol
outcomes in adolescents with ADHD.
AB - Escalations in alcohol use during adolescence may be linked with exposure to
negative life events, but most of this research has focused on between-person
associations. Moreover, adolescents with attention-deficit hyperactivity disorder
(ADHD) may be an especially vulnerable population, reporting more life events and
alcohol involvement and may even be more sensitive to the effects of life events
on alcohol outcomes compared with those without ADHD. We tested the between- and
within-person effects of the number and perceptions of negative life events on
the development of alcohol use outcomes from age 14 to 17 years in 259
adolescents with and without ADHD using generalized estimating equations. Between
person differences in exposure to negative life events across adolescence, but
not the perception of those events, were associated with a higher likelihood of
alcohol use and drunkenness at age 17 years. Within-person differences in life
events were associated with alcohol use above and beyond that predicted by an
adolescents' typical trajectory over time. Parent- and teacher-reported ADHD
symptoms were associated with more negative perceptions of life events and with
greater alcohol use and drunkenness at age 17 years, but symptoms did not
moderate the life event-alcohol association. Interventions should consider the
variables that produce vulnerability to life events as well as the immediate
impact of life events. That the accumulation of life events, rather than their
perceived negativity, was associated with alcohol outcomes indicates that
interventions targeting the reduction of negative events, rather than emotional
response, may be more protective against alcohol use in adolescence. (PsycINFO
Database Record
PMID- 28703611
TI - Smartphone-based, momentary intervention for alcohol cravings amongst individuals
with an alcohol use disorder.
AB - Smartphone-based alcohol interventions represent an innovative strategy for
providing in-the-moment intervention to individuals with an alcohol use disorder.
While early research into their overall effectiveness is promising, little is
known about the efficacy of specific intervention tools in reducing drinking
subsequent to a cued craving. This study examined the influence of smartphone
delivered in-the-moment coping strategies on drinking after experiencing a
craving among participants utilizing the Location-Based Monitoring and
Intervention for Alcohol Use Disorders (LBMI-A). The LBMI-A was utilized by 28
adults (18 to 45 years old) who met criteria for an alcohol use disorder and were
interested in changing their drinking. Participants utilized the system for 6
weeks and responded to a daily interview of craving, type of LBMI-A coping
strategy utilized in response, and whether or not they subsequently drank. Mixed
model analyses of 744 total observations revealed that craving cue type, craving
strength, and coping strategies were significantly related to drinking in
response to a craving. Results suggested that coping strategies delivered by the
LBMI-A (i.e., listening to an urge surfing audio file, viewing reasons for
changing drinking) were superior to using a non-LBMI-A strategy. Simple contrast
analyses indicated that cues related to being around alcohol and time of day were
the most potent elicitors of subsequent drinking. Results suggest smartphone
delivered coping strategies for alcohol cravings are effective in reducing
craving cued drinking and that craving cues related to drinking environments and
drinking times of day represent fruitful areas of intervention focus. (PsycINFO
Database Record
PMID- 28703612
TI - Target quit date timing as a predictor of smoking cessation outcomes.
AB - Evidence is mixed on whether timing of a target quit date (TQD) has an effect on
quit success. The purpose of this secondary analysis of data from a prospective
longitudinal study was to determine if time to TQD was a predictor of smoking
abstinence at follow-up. Between 2011 and 2013, a total of 5,793 adult smokers
participated in a 1-hr psychoeducation workshop and received 5 weeks of nicotine
patch treatment. All participants were required to indicate a TQD within 1 month
of the workshop. Latency to TQD was categorized into quartiles: 0 to 1 day (first
quartile: 28.1%); 2 to 6 days (second quartile: 22.4%); 7 to 19 days (third
quartile: 25.4%); 20-31 days (fourth quartile: 24.0%). Compared with participants
who chose an immediate TQD within 1 day of the workshop, odds of having quit
smoking at end-of-treatment and 6-month follow-up did not significantly differ
among those who set a TQD within 2-6 days (5-weeks: adjusted odds ratio [AOR] =
0.89, p = .315; 6-months: AOR = 0.89, p = .417), but were significantly lower for
those who chose a TQD either 7-19 days (5-weeks: AOR = 0.76, p = .023; 6-months:
AOR = 0.70, p = .013) or 20-31 days (5-weeks: AOR = 0.64, p = .001; 6-months: AOR
= 0.69, p = .017) after the workshop. TQD timing was an independent predictor of
smoking cessation outcomes after controlling for potential confounding variables
including confidence in quitting ability, importance of quitting, nicotine
dependence, and number of nicotine patches used. (PsycINFO Database Record
PMID- 28703613
TI - The association between nonmedical use of prescription drugs and extreme weight
control behavior among adolescents.
AB - Although extreme weight control behavior (EWCB) is associated with substance use,
no research has examined the association between the nonmedical use of
prescription drugs (NMUPD) and EWCB. Self-report data were collected from a
sample of 4,148 students in Grades 9-12 enrolled in 5 high schools across the
United States. Logistic regression models were constructed to examine the
nonmedical use of prescription pain relievers, depressants, stimulants, and a
composite measure for any NMUPD, and the EWCB of fasting, use of diet pills,
powders, or liquids, and vomiting or laxative use. Models were estimated before
and after controlling for key covariates for males and females. Approximately 16%
of respondents reported any EWCB during the past 30 days, while 11% reported any
NMUPD during the past 30 days. After covariate adjustment, any NMUPD was
associated with any EWCB in both males and females (p < .05), and all EWCB
remained significant in females who reported prescription pain reliever use (p <
.01), with 2 out of 3 remaining significant for prescription stimulant and
depressant use (p < .01). The only significant association detected for males was
between prescription pain reliever use and using diet pills, powders, or liquids
(OR = 2.2, p < .01). Results suggest significant associations between NMUPD and
EWCB, with variations by sex. These findings provide directions for additional
research and point to several potential identification and intervention efforts.
(PsycINFO Database Record
PMID- 28703614
TI - Peer alcohol behavior moderates within-level associations between posttraumatic
stress disorder symptoms and alcohol use in college students.
AB - Self-medication theory (SMT) posits that individuals exposed to trauma and
resulting posttraumatic stress symptoms (PTSD) are at risk for heavy drinking and
associated negative consequences. Close peer alcohol use is also a powerful
predictor of alcohol involvement in college, particularly influencing those with
greater negative affect. As individuals with PTSD may rely on peers for support,
peer drinking behaviors are possibly putting them at further risk for greater
alcohol use and resulting consequences. To test self-medication processes, the
present study examined the relationship between weekday PTSD symptoms, weekend
alcohol behavior, and the influence of both emotionally supportive peer and other
friend drinking behavior by investigating: (a) whether weekday PTSD symptoms
predicted subsequent weekend alcohol use and consequences; and (b) whether the
relationship between weekday PTSD symptoms and weekend alcohol behavior was
moderated by various drinking behaviors of one's peers. Trauma-exposed heavy
drinking college students (N = 128) completed a baseline assessment and 30 daily,
Web-based assessments of alcohol use and related consequences, PTSD symptoms, and
peer alcohol behavior. Results directly testing SMT were not supported. However,
friend alcohol behavior moderated the relationship between weekday PTSD and
weekend alcohol behavior. Findings highlight the importance of peer drinking as
both a buffer and risk factor for problematic drinking and provide useful
information for interventions aimed at high-risk drinkers. (PsycINFO Database
Record
PMID- 28703615
TI - A longitudinal study predicting adolescent tobacco, alcohol, and cannabis use by
behavioral characteristics of close friends.
AB - Few studies have examined in detail how specific behaviors of close friends put
adolescents at risk for specific types of substance use. Using a prospective,
longitudinal design, we examined how well the substance use of 248 young urban
adolescents was predicted by perceptions of their 3 closest friends' problematic
behaviors: (1) using substances, (2) offering substances, and (3) engaging with
friends in risky behavior (substance use, illegal behavior, violent behavior, or
high-risk sexual behavior). Longitudinal multivariate repeated measures models
were tested to predict tobacco, alcohol, and cannabis use and perceived closeness
was tested as a moderator of the effects of perceptions of problematic peer
behavior. Perceptions of peer substance use were significantly associated with
tobacco use, and closeness moderated the influence of peer substance use and
offers to use substances on tobacco use. Perceptions of problematic peer
behaviors were not significantly associated with alcohol use and closeness was
not significant as a moderator. Perceptions of peer substance use was
significantly associated with cannabis use, and closeness moderated the influence
of perceptions of peer risk behaviors, peer substance use, and offers to use
substances on cannabis use. Results implicate the importance of understanding
problematic peer behavior within the context of close, adolescent friendships.
Adolescents with close friends who were substance users, who made offers to use
substances, and who engaged in risky behaviors were more likely to use tobacco
and cannabis. Perceptions of young adolescents' close friends' behaviors
influenced their substance use up to 2 years later. (PsycINFO Database Record
PMID- 28703616
TI - The Protective Behavioral Strategies for Marijuana Scale: Further examination
using item response theory.
AB - Given recent state legislation legalizing marijuana for recreational purposes and
majority popular opinion favoring these laws, we developed the Protective
Behavioral Strategies for Marijuana scale (PBSM) to identify strategies that may
mitigate the harms related to marijuana use among those young people who choose
to use the drug. In the current study, we expand on the initial exploratory study
of the PBSM to further validate the measure with a large and geographically
diverse sample (N = 2,117; 60% women, 30% non-White) of college students from 11
different universities across the United States. We sought to develop a
psychometrically sound item bank for the PBSM and to create a short assessment
form that minimizes respondent burden and time. Quantitative item analyses,
including exploratory and confirmatory factor analyses with item response theory
(IRT) and evaluation of differential item functioning (DIF), revealed an item
bank of 36 items that was examined for unidimensionality and good content
coverage, as well as a short form of 17 items that is free of bias in terms of
gender (men vs. women), race (White vs. non-White), ethnicity (Hispanic vs. non
Hispanic), and recreational marijuana use legal status (state recreational
marijuana was legal for 25.5% of participants). We also provide a scoring table
for easy transformation from sum scores to IRT scale scores. The PBSM item bank
and short form associated strongly and negatively with past month marijuana use
and consequences. The measure may be useful to researchers and clinicians
conducting intervention and prevention programs with young adults. (PsycINFO
Database Record
PMID- 28703617
TI - Sleep quality in returning veterans: The influence of mild traumatic brain
injury.
AB - OBJECTIVE: Sleep disturbance is a key behavioral health concern among Iraq and
Afghanistan era veterans and is a frequent complaint among veterans with a
history of mild traumatic brain injury (mTBI). Currently, it is unclear whether
sleep disturbance is a core sequelae of mTBI or if it may be related to other
behavioral health conditions that are commonly present in postdeployment
veterans. The purpose of this study was to determine if history of mTBI is
associated with poor sleep quality beyond combat exposure and behavioral health
concerns, including posttraumatic stress disorder (PTSD), mood disorders, anxiety
disorders, and substance use disorders. RESEARCH METHOD: Participants included
527 veterans who deployed after September 11, 2001, in support of the wars in
Iraq and Afghanistan. Participants completed the Structured Clinical Interview
for DSM-IV Disorders, Combat Exposure Scale, a structured clinical TBI interview,
and the Pittsburgh Sleep Quality Index. RESULTS: Deployment-related mTBI was
associated with poor sleep quality independent of combat exposure, PTSD, mood
disorders, anxiety disorders, and substance use disorders (B = 1.84, p = .001) an
average of 6 years after the injury event. No interaction effects between
deployment-related mTBI and combat exposure, PTSD, mood disorders, anxiety
disorders, or substance use disorders on sleep quality were detected.
CONCLUSIONS: Veterans with a history of mTBI sustained during deployment reported
significantly poorer sleep quality than veterans without history of mTBI, even
when considering combat exposure and behavioral health issues. Clinicians should
consider mTBI as a potential contributor to sleep problems, even years after an
injury event. (PsycINFO Database Record
PMID- 28703618
TI - From conscious thought to automatic action: A simulation account of action
planning.
AB - We provide a theoretical framework and empirical evidence for how verbally
planning an action creates direct perception-action links and behavioral
automaticity. We argue that planning actions in an if (situation)-then (action)
format induces sensorimotor simulations (i.e., activity patterns reenacting the
event in the sensory and motor brain areas) of the anticipated situation and the
intended action. Due to their temporal overlap, these activity patterns become
linked. Whenever the previously simulated situation is encountered, the
previously simulated action is partially reactivated through spreading activation
and thus more likely to be executed. In 4 experiments (N = 363), we investigated
the relation between specific if-then action plans worded to activate simulations
of elbow flexion versus extension movements and actual elbow flexion versus
extension movements in a subsequent, ostensibly unrelated categorization task. As
expected, linking a critical stimulus to intended actions that implied elbow
flexion movements (e.g., grabbing it for consumption) subsequently facilitated
elbow flexion movements upon encountering the critical stimulus. However, linking
a critical stimulus to actions that implied elbow extension movements (e.g.,
pointing at it) subsequently facilitated elbow extension movements upon
encountering the critical stimulus. Thus, minor differences (i.e., exchanging the
words "point at" with "grab") in verbally formulated action plans (i.e.,
conscious thought) had systematic consequences on subsequent actions. The
question of how conscious thought can induce stimulus-triggered action is
illuminated by the provided theoretical framework and the respective empirical
evidence, facilitating the understanding of behavioral automaticity and human
agency. (PsycINFO Database Record
PMID- 28703619
TI - The nature of short-term consolidation in visual working memory.
AB - Short-term consolidation is the process by which stable working memory
representations are created. This process is fundamental to cognition yet poorly
understood. The present work examines short-term consolidation using a Bayesian
hierarchical model of visual working memory recall to determine the underlying
processes at work. Our results show that consolidation functions largely through
changing the proportion of memory items successfully maintained until test.
Although there was some evidence that consolidation affects representational
precision, this change was modest and could not account for the bulk of the
consolidation effect on memory performance. The time course of the consolidation
function and selective influence of consolidation on specific serial positions
strongly indicates that short-term consolidation induces an attentional blink.
The blink leads to deficits in memory for the immediately following item when
time pressure is introduced. Temporal distinctiveness accounts of the
consolidation process are tested and ruled out. (PsycINFO Database Record
PMID- 28703620
TI - Is general intelligence little more than the speed of higher-order processing?
AB - Individual differences in the speed of information processing have been
hypothesized to give rise to individual differences in general intelligence.
Consistent with this hypothesis, reaction times (RTs) and latencies of event
related potential have been shown to be moderately associated with intelligence.
These associations have been explained either in terms of individual differences
in some brain-wide property such as myelination, the speed of neural
oscillations, or white-matter tract integrity, or in terms of individual
differences in specific processes such as the signal-to-noise ratio in evidence
accumulation, executive control, or the cholinergic system. Here we show in a
sample of 122 participants, who completed a battery of RT tasks at 2 laboratory
sessions while an EEG was recorded, that more intelligent individuals have a
higher speed of higher-order information processing that explains about 80% of
the variance in general intelligence. Our results do not support the notion that
individuals with higher levels of general intelligence show advantages in some
brain-wide property. Instead, they suggest that more intelligent individuals
benefit from a more efficient transmission of information from frontal attention
and working memory processes to temporal-parietal processes of memory storage.
(PsycINFO Database Record
PMID- 28703621
TI - Attentional accounting: Voluntary spatial attention increases budget category
prioritization.
AB - Too often, people fail to prioritize the most important activities, life domains,
and budget categories. One reason for misplaced priorities, we argue, is that
activities and categories people have frequently or recently attended to seem
higher priority than other activities and categories. In Experiment 1,
participants were cued to direct voluntary spatial attention toward 1 side of a
screen while images depicting different budget categories were presented: 1
category on the cued side and 1 on the noncued side of the screen. Participants
rated cued budget categories as higher priority than noncued budget categories.
Cued attention also increased perceived distinctiveness, and a mediation model
was consistent with the hypothesis that distinctiveness mediates the effect of
cued attention on prioritization. Experiment 2 orthogonally manipulated 2
components of a spatial cuing manipulation-heightened visual attention and
heightened mental attention-to examine how each influences prioritization. Visual
attention and mental attention additively increased prioritization. In Experiment
3, attention increased prioritization even when prioritization decisions were
incentivized, and even when heightened attention was isolated from primacy and
recency. Across experiments, cued categories were prioritized more than noncued
categories even though measures were taken to disguise the purpose of the
experiments and manipulate attention incidentally (i.e., as a by-product of an
unrelated task). (PsycINFO Database Record
PMID- 28703622
TI - Recommendations for SIR-Spheres Y-90 resin microspheres in chemotherapy
refractory/intolerant colorectal liver metastases.
AB - A Spanish expert panel reviewed current evidence for the use of SIR-Spheres Y-90
resin microspheres in patients with chemotherapy refractory/intolerant
unresectable colorectal liver metastases. Substantial evidence for its efficacy
and safety is available from a randomized controlled study, retrospective
comparative studies and several single arm studies. Clinical evidence data
obtained from more than 1500 patients have led to the inclusion of selective
internal radiation therapy in the 2016 ESMO Clinical Guidelines as third-line
treatment. This publication results from an expert panel meeting, where published
evidence and author's experiences were shared to position SIR-Spheres Y-90 resin
microspheres in Spain for the treatment of chemotherapy refractory/intolerant
unresectable colorectal liver metastases, and second, to define the patient
subgroup that will benefit the most with this treatment.
PMID- 28703623
TI - Opinions and attitudes of obstetricians and midwives in Turkey towards caesarean
section and vaginal birth following a previous caesarean section.
AB - Aim To determine the opinions and attitudes of Turkish obstetricians and midwives
to caesarean section (C-section) and vaginal birth following a C-section. Methods
The study involved obstetricians and midwives who were working in a state women's
hospital and two private hospitals in Gaziantep, Turkey. Participants were asked
to complete questionnaires on sociodemographic data and provide opinions about C
section. Results A total of 88 midwives and 22 obstetricians participated in the
study. Approximately one-third of midwives believed caesarean rates were high at
their institution and more than 50% thought that the rate should be reduced. In
contrast, although approximately 80% of obstetricians thought that caesarean
rates in their institutions ranged between 25-50%, only 18% believed the rate was
high and 68% believed that the rate of should be reduced. Midwives and
obstetricians tended to agree on most suggested reasons for high C-section rates.
When asked about interventions that may reduce the C-section rates, midwives and
obstetricians had opposing views. However, most participants agreed that prenatal
childbirth preparation courses would be beneficial. Conclusions This study showed
that most midwives and obstetricians believe the rate of C-section at their
institution is high and should be reduced.
PMID- 28703624
TI - Cabozantinib in the treatment of hepatocellular carcinoma.
AB - Despite clinical studies with different mechanisms of action, no new systemic
therapies were approved for hepatocellular carcinoma (HCC) between sorafenib in
2007 and regorafenib in 2017. This is an area of interest to improve outcomes and
quality of life. Cabozantinib is oral, small-molecule tyrosine kinase inhibitor
that primarily targets MET, VEGFR2, AXL and RET, with additional effect on KIT
and FLT3. Cabozantinib is approved for progressive metastatic medullary thyroid
cancer and previously treated renal cell carcinoma, and is in development for
multiple solid tumors. Given positive results from a Phase II study, cabozantinib
is under evaluation in a Phase III randomized controlled trial for patients with
advanced HCC previously treated with sorafenib. It has been granted orphan drug
status in the USA for this indication. This review summarizes the development of
cabozantinib in HCC.
PMID- 28703625
TI - Characterization and Application of Antilisterial Enterocins on Model Fresh
Cheese.
AB - Enterococcus faecalis strains isolated from an artisanal cheese were selected
based on enterocin production against Listeria monocytogenes. The strains formed
biofilms and presented high hydrophobic character and good autoaggregation and
coaggregation capacity with L. monocytogenes. Strains L3A21M3 and L3B1K3
presented high survival under gastrointestinal conditions, were able to adhere to
human intestinal cells (Caco-2 and HT-29), and blocked the adhesion and invasion
of L. monocytogenes. The antilisterial activity of enterocins was not affected by
pH (2 to 12), heating (100 degrees C), and chemical and surfactant agents.
However, strains L3A21M3 and L3A21M8 produced thermolabile enterocins, which were
also sensible to extreme pH values. Enterocins exhibited a bacteriostatic mode of
action against L. monocytogenes, and maximum production was observed during the
stationary phase. Common enterocin structural genes were not detected by PCR
amplification with specific primers, although an exhaustive screening was not
performed. The enterocin produced by the L3B1K3 strain was purified and applied
to model cheeses contaminated with L. monocytogenes. This enterocin reduced
survival of L. monocytogenes on fresh cheeses in a dose-dependent manner. The
highest dose tested (2,048 arbitrary units per g of cheese) was effective in
reducing the pathogen counts to undetectable values throughout storage (6 to 72
h). These results suggest that these strains have great potential to be used as
biopreservatives in the food industry and also as probiotics, with the potential
to prevent L. monocytogenes gastrointestinal infection.
PMID- 28703626
TI - Increasing proportion of ST elevation myocardial infarction patients with
coronary atherosclerosis poorly explained by standard modifiable risk factors.
AB - Aims Identification and management of the Standard Modifiable Cardiovascular Risk
Factors (SMuRFs; hypercholesterolaemia, hypertension, diabetes and smoking) has
substantially improved cardiovascular disease outcomes. However, cardiovascular
disease remains the leading cause of death worldwide. Suspecting an evolving
pattern of risk factor profiles in the ST elevation myocardial infarction (STEMI)
population with the improvements in primary care, we hypothesized that the
proportion of 'SMuRFless' STEMI patients may have increased. Methods/results We
performed a single centre retrospective study of consecutive STEMI patients
presenting from January 2006 to December 2014. Over the study period 132/695
(25%) STEMI patients had 0 SMuRFs, a proportion that did not significantly change
with age, gender or family history. The proportion of STEMI patients who were
SMuRFless in 2006 was 11%, which increased to 27% by 2014 (odds ratio 1.12 per
year, 95% confidence interval: 1.04-1.22). The proportion of patients with
hypercholesterolaemia decreased (odds ratio 0.92, 95% confidence interval 0.86
0.98), as did the proportion of current smokers (odds ratio 0.93, 95% confidence
interval 0.86-0.99), with no significant change in the proportion of patients
with diabetes and hypertension. SMuRF status was not associated with extent of
coronary disease; in-hospital outcomes, or discharge prescribing patterns.
Conclusion The proportion of STEMI patients with STEMI poorly explained by SMuRFs
is high, and is significantly increasing. This highlights the need for bold
approaches to discover new mechanisms and markers for early identification of
these patients, as well as to understand the outcomes and develop new targeted
therapies.
PMID- 28703627
TI - Increased augmentation index and central systolic arterial pressure are
associated with lower school and motor performance in young adolescents.
AB - Objective In adults, improper arterial function has been linked to cognitive
impairment. The pulse wave velocity (PWV), augmentation index (AIx) and other
vascular parameters are useful indicators of arterial health. In our study, we
monitored arterial properties, body constitution, school success, and motor
skills in young adolescents. We hypothesize that reduced cognitive and motor
abilities have a vascular origin in children. Methods We analysed 81 healthy
school children aged 11-16 years. Anthropometry central systolic arterial
pressure, body mass index (BMI), standard deviation scores (SDS) BMI, general
school performance grade, and eight motor tests were assessed. PWV, AIx, and
central systolic arterial pressure (SBPao) were measured. Results AIx and SBPao
correlated negatively with school performance grades. Extremely high AIx, PWV and
SBPao values were observed in 5% of children and these children had average to
low school performance. PWV correlated significantly with weight, height, and
waist and hip circumference. AIx, PWV, school success, and BMI correlated
strongly with certain motor functions. Conclusions Increased AIx and SBPao are
associated with lower school and motor performance in children. PWV is influenced
by the body's constitution.
PMID- 28703628
TI - Correction to: Castedal et al., IFN-free sofosbuvir-based treatment of post
transplant hepatitis C relapse - a Swedish real life experience.
PMID- 28703629
TI - Experiences of women who participated in a beta-test for an online-streamed yoga
intervention after a stillbirth.
AB - BACKGROUND: Little is known about how to best care for mothers after stillbirth.
As such, this paper will report the satisfaction and perceptions of an online
yoga intervention (12-week beta test) in women after stillbirth. METHODS:
Participants (n=74) had a stillbirth within the last 24-months (M time since loss
9.65 +/- 6.9 months). Post-intervention satisfaction surveys and interviews and
dropout surveys were conducted. Descriptive statistics were used to analyze
survey responses and demographic information. A phenomenological approach was
used to explore and understand unique experiences of participant interviews. Data
were analyzed using NVivo10. RESULTS: Twenty-six women (M age 33.73 +/- 4.38) we
re completers (> 3 wks of yoga), 26 (M age 31.82 +/- 4.13) were non-completers (<
3 wks of yoga), and 22 (M age 32.94 +/- 2.93) dropped out. Twenty completers
participated in a post-intervention satisfaction survey with 75% (n=15) reporting
being very satisfied or satisfied with the online yoga intervention, found it to
be very enjoyable or enjoyable, and very helpful or helpful to cope with grief.
Satisfaction and perceptions of the intervention in those who completed an
interview (n=12) were clustered around the following themes: benefits, barriers,
dislikes, satisfaction, and preferences. Of the 22 dropouts, 14 completed a
dropout survey. Women withdrew from the study due to pregnancy (n=3, 21%), burden
(n=3, 21%), stress (n=2, 14%), lack of time (n=2, 14%), did not enjoy (n=1, 7%),
and other (n=3, 21%). CONCLUSION: Findings here may be used to help design future
research.
PMID- 28703630
TI - The adaption and evaluation of a Latvian version of the National Institutes of
Health Stroke Scale.
AB - Objectives To determine the validity and reliability of a Latvian version of the
National Institutes of Health Stroke Scale (LV-NIHSS) for evaluating Latvian
stroke patients. Methods The adaption of the LV-NIHSS followed standard methods
used for the adaption and validation of clinical assessment tools. The scale
validity was tested by comparison with the Glasgow Coma Scale (GCS) and the
modified Rankin scale (mRs). The reliability of the LV-NIHSS was evaluated by
intra-rater and inter-rater agreement using intra-class correlation coefficient
(ICC) analysis. Results A total of 296 stroke patients and 101 control subjects
were evaluated. The mean age of the overall study population was 73.6 years
(range, 37 - 94 years; 227 [57.2%] were female). The mean LV-NIHSS score of the
patients with stroke was 8.4 +/- 6.2. In terms of construct validity of the LV
NIHSS, it correlated with the GCS ( r = -0.571) and mRs ( r = 0.755). In terms of
the reliability of the LV-NIHSS, the inter-rater agreement had an ICC of 0.99 and
the intra-rater agreement had an ICC of 0.99. Conclusion The adaption of LV-NIHSS
was successful and the evaluation showed that the scale was valid and reliable
for evaluating Latvian stroke patients.
PMID- 28703631
TI - Silicotuberculosis with oesophagobronchial fistulas and broncholithiasis: a case
report.
AB - A 76-year-old woman was admitted to the hospital four times from November 2007 to
June 2009. In this complex case, the patient had silicosis complicated by
broncholithiasis, oesophagobronchial fistulas, and relapsed tuberculosis. She had
worked as a stone crusher for 3 years and was exposed to a large amount of quartz
dust. Barium oesophagography, gastroesophageal endoscopy, and biopsy suggested
oesophageal-related chronic inflammation and ulceration, which may have caused
the repeated oesophagobronchial fistulas. Bronchoscopy revealed a free
broncholithiasis in the left mainstem bronchus. The patient was admitted a fourth
time because of silicotuberculosis relapse. After 9 months of antituberculosis
treatment, the patient recovered and was still clinically well at the time of
this writing.
PMID- 28703632
TI - Clinical characteristics and cytokine changes in children with pneumonia
requiring mechanical ventilation.
AB - Objective To assess clinical characteristics and cytokine levels in children with
severe pneumonia who required ventilatory support. Methods In this prospective,
descriptive, cross-sectional study, blood and endotracheal fluid samples were
obtained from patients with severe pneumonia, aged <5 years, within 24 h
following intubation. Blood samples were also obtained from age-matched healthy
controls. Cytokine levels were investigated using flow cytometry-assisted
immunoassay. Results Forty-five patients with severe pneumonia requiring
mechanical ventilation (aged 10 +/- 5 months) and 35 healthy age-matched controls
were included. Patients with severe pneumonia had significantly increased serum
interleukin (IL)-6, IL-8, and granulocyte/macrophage colony-stimulating factor
concentrations compared with controls (80.84 pg/ml versus 2.06 pg/ml, 90.03 pg/ml
versus 6.62 pg/ml, and 115.58 pg/ml versus 11.47 pg/ml, respectively). In the
severe pneumonia group, serum IL-10 levels were significantly higher in patients
aged <6 months versus those aged 6-12 months. Age-group differences in serum
cytokine levels did not correspond to age-group differences in endotracheal-fluid
cytokine levels. Serum IL-6 levels were significantly higher in patients who
subsequently died versus those who survived (267.12 pg/ml versus 20.75 pg/ml,
respectively). Conclusion High IL-6 concentrations were associated with mortality
in patients <5 years of age with severe pneumonia requiring mechanical
ventilation.
PMID- 28703633
TI - Retrospective analysis of the effect of acid-suppressant therapy on
clinicopathologic parameters of cats with chronic kidney disease.
AB - Objectives The aim was to retrospectively evaluate the effects of acid
suppressant therapy in a population of cats with chronic kidney disease (CKD).
The study objectives were to evaluate the effects of acid-suppressant therapy on
clinicopathologic variables and progression of CKD over time. Methods The
databases of two institutions were searched over an 11 year time span for cats
fitting inclusion criteria for CKD. A total of 89 cats met the criteria for
inclusion and were grouped according to either early (ie, stages 1-2) or advanced
(ie, stages 3-4) CKD. Variables were statistically analyzed before and after
treatment with either: (1) proton pump inhibitors (PPIs; n = 17), (2) histamine-2
receptor antagonists (H2RAs; n = 30), (3) combined acid-suppressant therapy (PPI
+ H2RA; n = 6) or (4) no acid-suppressant therapy (n = 36). Shapiro-Wilk testing
and Q-Q plots were used to assess normality and variance, respectively. A
complete randomized design with a mixed-effects repeated measures ANOVA was used
to evaluate for differences in stage, treatment and time, as well as the
interaction between these effects. Results A significant increase in blood
creatinine concentration was found over time independent of severity of CKD and
treatment group ( P = 0.0087). A significant increase in blood sodium
concentration (change of 3.12 mmol/l) was found independent of stage in cats
receiving PPI therapy ( P = 0.0109). A significant decrease in total blood
magnesium (change of 0.15 mmol/l) was detected in two cats with early CKD
receiving combined acid suppressants ( P = 0.0025). Conclusions and relevance
Results of this retrospective study suggest that cats with CKD receiving PPI
therapy may develop alterations in blood sodium concentrations but do not
experience more rapid progression of CKD.
PMID- 28703634
TI - The profile of leucocytes, CD3+, CD4+, and CD8+ T cells, and cytokine
concentrations in peripheral blood of children with acute asthma exacerbation.
AB - Objective To determine the leucocyte profile and cytokine concentrations in the
peripheral blood of children with an acute asthma exacerbation (AAE). Methods
This descriptive, cross-sectional study enrolled paediatric patients admitted to
hospital for AAE. The severity of AAE was assessed using the paediatric asthma
score (PAS). Peripheral blood samples were collected for automatic quantification
of white blood cell counts, CD3+, CD4+, and CD8+ T cells populations by flow
cytometry and cytokine concentrations by flow cytometry-assisted immunoassay.
Results A total of 127 children with AAE and 30 healthy control subjects were
included in the study. The proportion of paediatric patients with decreased CD3+,
CD4+ and CD8+ T cells was significantly higher in those with severe AAE compared
with those with mild-to-moderate AAE. The concentrations of interleukin (IL)-2,
IL-8, IL-12, and IL-4 in paediatric patients with rhinovirus infection were
significantly higher than in those without rhinovirus infection. IL-2, IL-4, IL
6, TNF-alpha and GM-CSF concentrations during AAE were significantly lower than
control. IL-5 and IL-13 concentrations during AAE were significantly higher than
control. Conclusions The decrease of CD3+, CD4+, CD8+ T cells and IL-2, IL-4, IL
6, TNF-alpha, and GM-CSF combined with the increase of IL-5 and IL-13, were
associated with AAE in children with asthma.
PMID- 28703635
TI - Quantitative diffusion tensor imaging analysis does not distinguish pediatric
canines with mucopolysaccharidosis I from control canines.
AB - Purpose We compared fractional anisotropy and radial diffusivity measurements
between pediatric canines affected with mucopolysaccharidosis I and pediatric
control canines. We hypothesized that lower fractional anisotropy and higher
radial diffusivity values, consistent with dysmyelination, would be present in
the mucopolysaccharidosis I cohort. Methods Six canine brains, three affected
with mucopolysaccharidosis I and three unaffected, were euthanized at 7 weeks and
imaged using a 7T small-animal magnetic resonance imaging system. Average
fractional anisotropy and radial diffusivity values were calculated for four
white-matter regions based on 100 regions of interest per region per specimen. A
95% confidence interval was calculated for each mean value. Results No difference
was seen in fractional anisotropy or radial diffusivity values between
mucopolysaccharidosis affected and unaffected brains in any region. In
particular, the 95% confidence intervals for mucopolysaccharidosis affected and
unaffected canines frequently overlapped for both fractional anisotropy and
radial diffusivity measurements. In addition, in some brain regions a large range
of fractional anisotropy and radial diffusivity values were seen within the same
cohort. Conclusion The fractional anisotropy and radial diffusivity values of
white matter did not differ between pediatric mucopolysaccharidosis affected
canines and pediatric control canines. Possible explanations include: (a) a lack
of white matter tissue differences between mucopolysaccharidosis affected and
unaffected brains at early disease stages; (b) diffusion tensor imaging does not
detect any existing differences; (c) inflammatory processes such as astrogliosis
produce changes that offset the decreased fractional anisotropy values and
increased radial diffusivity values that are expected in dysmyelination; and (d)
our sample size was insufficient to detect differences. Further studies
correlating diffusion tensor imaging findings to histology are warranted.
PMID- 28703636
TI - Therapeutic targeting in nanomedicine: the future lies in recombinant antibodies.
AB - The unique chemical and functional properties of nanoparticles can be harnessed
for the delivery of large quantities of various therapeutic biomolecules. Active
targeting of nanoparticles by conjugating ligands that bind to target cells
strongly facilitates accumulation, internalization into target cells and longer
retention at the target site, with consequent enhanced therapeutic effects.
Recombinant antibodies with high selectivity and availability for a vast range of
targets will dominate the future. In this review, we systematically outline the
tremendous progress in the conjugation of antibodies to nanoparticles and the
clear advantages that recombinant antibodies offer in the therapeutic targeting
of nanoparticles. The demonstrated flexibility of recombinant antibody coupling
to nanoparticles highlights the bright future of this technology for modern
therapeutic nanomedicine.
PMID- 28703637
TI - Learning to Read a Semitic Abjad: The Triplex Model of Hebrew Reading
Development.
AB - We introduce a model of Hebrew reading development that emphasizes both the
universal and script-specific aspects of learning to read a Semitic abjad. At the
universal level, the study of Hebrew reading acquisition offers valuable insights
into the fundamental dilemmas of all writing systems-balancing the competing
needs of the novice versus the expert reader (Share, 2008). At the script
specific level, pointed Hebrew initially employs supplementary vowel signs,
providing the beginning reader a consistent, phonologically well-specified script
while helping the expert-to-be unitize words and morphemes via (consonantal)
spelling constancy. A major challenge for the developing Hebrew reader is
negotiating the transition from pointed to unpointed Hebrew, with its abundance
of homographs. Our triplex model emphasizes three phases of early Hebrew reading
development: a progression from lower-order, phonological (sublexical) sequential
spelling-to-sound translation (Phase 1, Grade 1) to higher-order, string-level
(lexical) lexico-morpho-orthographic processing (Phase 2, Grade 2) followed, in
the upper elementary grades, by a supralexical contextual level (Phase 3)
essential for dealing with the pervasive homography of unpointed Hebrew.
PMID- 28703638
TI - Global Increases in Individualism.
AB - Individualism appears to have increased over the past several decades, yet most
research documenting this shift has been limited to the study of a handful of
highly developed countries. Is the world becoming more individualist as a whole?
If so, why? To answer these questions, we examined 51 years of data on
individualist practices and values across 78 countries. Our findings suggest that
individualism is indeed rising in most of the societies we tested. Despite
dramatic shifts toward greater individualism around the world, however, cultural
differences remain sizable. Moreover, cultural differences are primarily linked
to changes in socioeconomic development, and to a lesser extent to shifts in
pathogen prevalence and disaster frequency.
PMID- 28703639
TI - Physicochemical regulation of TGF and VEGF delivery from mesoporous calcium
phosphate bone substitutes.
AB - AIM: Determination of the physicochemical parameters governing growth factors
(GFs) adsorption and release from mesoporous calcium phosphate ceramics.
MATERIALS & METHODS: Six mesoporous calcium phosphate ceramics prepared by soft
and hard templating were loaded with two different physiological concentrations
of TGF-beta1 or VEGF165 and their in vitro kinetics of adsorption/release were
studied. RESULTS: This low GF loading promotes adsorption on the highest binding
sites. The usually encountered detrimental burst release is thus considerably
reduced for samples prepared by hard-templating method. CONCLUSION: Our findings
highlight that the strong affinity of GFs with the ceramic surfaces, demonstrated
by a slow GFs release, is enhanced by the large surface area, confinement into
mesopores of ceramics and high difference of surface charge between ceramic
surfaces and GFs.
PMID- 28703640
TI - Serum cortisol mediates the relationship between fecal Ruminococcus and brain N
acetylaspartate in the young pig.
AB - A dynamic relationship between the gut microbiota and brain is pivotal in
neonatal development. Dysbiosis of the microbiome may result in altered
neurodevelopment; however, it is unclear which specific members of microbiota are
most influential and what factors might mediate the relationship between the gut
and the brain. Twenty-four vaginally-derived male piglets were subjected to
magnetic resonance spectroscopy at 30 d of age. Ascending colon contents, feces,
and blood were collected and analyzed for volatile fatty acids, microbiota
relative abundance by 16s rRNA, and serum metabolites, respectively. A mediation
analysis was performed to assess the mediatory effect of serum biomarkers on the
relationship between microbiota and neurometabolites. Results indicated fecal
Ruminococcus and Butyricimonas predicted brain N-acetylaspartate (NAA). Analysis
of serum biomarkers indicated Ruminococcus independently predicted serum
serotonin and cortisol. A 3-step mediation indicated: i) Ruminococcus negatively
predicted NAA, ii) Ruminococcus negatively predicted cortisol, and iii) a
significant indirect effect (i.e., the effect of fecal Ruminococcus through
cortisol on NAA) was observed and the direct effect became insignificant. Thus,
serum cortisol fully mediated the relationship between fecal Ruminococcus and
brain NAA. Using magnetic resonance spectroscopy, this study used a statistical
mediation analysis and provides a novel perspective into the potential underlying
mechanisms through which the microbiota may shape brain development. This is the
first study to link Ruminococcus, cortisol, and NAA in vivo, and these findings
are substantiated by previous literature indicating these factors may be
influential in the etiology of neurodevelopmental disorders.
PMID- 28703641
TI - Health Care Access for Adults With Intellectual and Developmental Disabilities: A
Scoping Review.
AB - Adults with intellectual and/or developmental disabilities (IDD) often experience
health disparities. To address disparities, Healthy People 2020 includes specific
disability and health goals focused on improving health care access. The study's
purpose was to review the literature exploring health care access for adults with
IDD to identify opportunities for occupational therapy research and practice. A
scoping review was completed of articles discussing health care access among
adults with IDD in the United States. Thirty-seven articles met the inclusion
criteria. Results are framed using the ecology of human performance theory
identifying person and environmental issues affecting health care access of
adults with IDD. Opportunities exist for occupational therapy to improve
participation and health of adults with IDD through engaging in research and
practice efforts addressing health care access. Occupational therapy could
develop interventions to establish skills and abilities and recommend changes to
the health care environment.
PMID- 28703642
TI - WideCells Group PLC.
AB - WideCells Group PLC (Manchester, UK) is a global stem cell services company with
the aim of leading a transformation in cord blood banking and stem cell
treatment. There are three key divisions: WideCells, WideAcademy and CellPlan.
WideCells provides contract, collaborative and in-house research, and stem cell
processing and storage facilities for a wide range of human tissues. WideAcademy,
the education and training branch of the WideCells Group, aims to become the
thought leader in stem cell technology, influencing and informing the next
generation of healthcare professionals working in stem cell technology. CellPlan
is a first-of-its-kind medical insurance plan to make stem cell treatment
accessible and affordable by providing access to renowned specialists and
hospitals globally with financial cover for cord blood transplantation and for
participation in clinical trials using cord blood.
PMID- 28703643
TI - Methotrexate and beta-carotene loaded-lipid polymer hybrid nanoparticles: a
preclinical study for breast cancer.
AB - AIM: This work was intended to investigate the targeting potential of fructose
tethered lipid-polymeric hybrid nanoparticles (F-BC-MTX-LPHNPs) co-loaded with
beta carotene (BC) and methotrexate (MTX) in breast cancer therapeutics and find
out the possible protective role of BC on MTX-induced toxicity. MATERIALS &
METHODS: F-BC-MTX-LPHNPs were fabricated using self-assembled nano-precipitation
technique. Fructose was conjugated on the surface of the particles. The in vitro
cytotoxicity, sub-cellular localization and apoptotic activity of F-BC-MTX-LPHNPs
were evaluated against MCF-7 breast cancer cells. The antitumor potential of F-BC
MTX-LPHNPs was further studied. RESULTS & CONCLUSION: Outcomes suggested that F
BC-MTX-LPHNPs induced the highest apoptosis index (0.89) against MCF-7 cells.
Following 30 days of treatment, the residual tumor progression was assessed to be
approximately 32%, in animals treated with F-BC-MTX-LPHNPs. F-BC-MTX-LPHNPs are
competent to selectively convey the chemotherapeutic agent to the breast cancers.
Beta carotene ameliorated MTX-induced hepatic and renal toxicity.
PMID- 28703644
TI - Effects of Phase Aberration and Phase Aberration Correction on the Minimum
Variance Beamformer.
AB - The minimum variance (MV) beamformer has the potential to enhance the resolution
and contrast of ultrasound images but is sensitive to steering vector errors.
Robust MV beamformers have been proposed but mainly evaluated in the presence of
gross sound speed mismatches, and the impact of phase aberration correction (PAC)
methods in mitigating the effects of phase aberration in MV beamformed images has
not been explored. In this study, an analysis of the effects of aberration on
conventional MV and eigenspace MV (ESMV) beamformers is carried out. In addition,
the impact of three PAC algorithms on the performance of MV beamforming is
analyzed. The different beamformers were tested on simulated data and on
experimental data corrupted with electronic and tissue-based aberration. It is
shown that all gains in performance of the MV beamformer with respect to delay
and-sum (DAS) are lost at high aberration strengths. For instance, with an
electronic aberration of 60 ns, the lateral resolution of DAS degrades by 17%
while MV degrades by 73% with respect to the images with no aberration. Moreover,
although ESMV shows robustness at low aberration levels, its degradation at
higher aberrations is approximately the same as that of regular MV. It is also
shown that basic PAC methods improve the aberrated MV beamformer. For example, in
the case of electronic aberration, multi-lag reduces degradation in lateral
resolution from 73% to 28% and contrast loss from 85% to 25%. These enhancements
allow the combination of MV and PAC to outperform DAS and PAC and ESMV in
moderate and strong aberrations. We conclude that the effect of aberration on the
MV beamformer is stronger than previously reported in the literature and that PAC
is needed to improve its clinical potential.
PMID- 28703645
TI - An analysis of topics and vocabulary in Chinese oral narratives by normal
speakers and speakers with fluent aphasia.
AB - This study analysed the topic and vocabulary of Chinese speakers based on
language samples of personal recounts in a large spoken Chinese database recently
made available in the public domain, i.e. Cantonese AphasiaBank (
http://www.speech.hku.hk/caphbank/search/ ). The goal of the analysis is to offer
clinicians a rich source for selecting ecologically valid training materials for
rehabilitating Chinese-speaking people with aphasia (PWA) in the design and
planning of culturally and linguistically appropriate treatments. Discourse
production of 65 Chinese-speaking PWA of fluent types (henceforth, PWFA) and
their non-aphasic controls narrating an important event in their life were
extracted from Cantonese AphasiaBank. Analyses of topics and vocabularies in
terms of part-of-speech, word frequency, lexical semantics, and diversity were
conducted. There was significant overlap in topics between the two groups. While
the vocabulary was larger for controls than that of PWFA as expected, they were
similar in distribution across parts-of-speech, frequency of occurrence, and the
ratio of concrete to abstract items in major open word classes. Moreover,
proportionately more different verbs than nouns were employed at the individual
level for both speaker groups. The findings provide important implications for
guiding directions of aphasia rehabilitation not only of fluent but also non
fluent Chinese aphasic speakers.
PMID- 28703646
TI - Clinical features of patients who died within 24 h after admission to a stroke
care center.
AB - Objective In Japan, stroke care is provided through medical cooperation and
standardized treatment. However, various factors affect mortality in the
hyperacute phase. The present study investigated factors associated with death
within 24 h after admission for acute stroke. Methods Among 2335 patients
admitted within 24 h after stroke onset from 1 January 2007 to 31 December 2012,
a total of 139 deaths occurred. Forty-eight deaths occurred within 24 h after
admission. We retrospectively examined the clinical features of these 48
patients. Results The overall mortality rate was 6.0%. When the initial 72-h
period was divided into <=24 h (Period I), >24 to 48 h (Period II), and >48 to 72
h (Period III), deaths were significantly more frequent in Period I than in the
other two periods. The frequency of intracerebral haemorrhage (ICH) was also
significantly higher in Period I than in the other two periods. Factors
significantly associated with death from ICH were systolic blood pressure,
hematoma volume, and surgery. Conclusion The mortality rate was low among
patients with stroke transported to the authors' medical center within 24 h of
onset. Blood pressure management and the timing of determining indications for
surgery are important factors in acute haemorrhagic stroke care.
PMID- 28703647
TI - Ulnar Nerve Injury as a Result of Galeazzi Fracture: A Case Report and Literature
Review.
AB - BACKGROUND: Sparse documentation of Galeazzi fracture with associated nerve
injury exists in the medical literature. The purpose of this report is to review
the available literature in regard to incidence, nerve injury type, treatment
strategies, and expected outcomes. METHODS: We present a classic Galeazzi
fracture dislocation with associated complete ulnar nerve transection injury at
the level of the wrist. After rigid internal bony stabilization, allograft nerve
repair was performed. The patient's presentation, operative management, recovery,
and a thorough literature review are discussed. RESULTS: Fracture union was
attained with near full wrist and elbow range of motion. Despite lack of ulnar
nerve function return, the patient was able to resume manual labor occupation.
CONCLUSIONS: Despite its close proximity to the dislocating distal radioulnar
joint (DRUJ), thorough review reveals rare associated ulnar nerve palsy. If there
is suspicion for nerve injury in the setting of open DRUJ dislocation, the nerve
should be explored to identify possible entrapment or transection. Literature
supports likely return of nerve function in cases of intact nerve; however,
management of nerve transection remains debatable.
PMID- 28703648
TI - Temporal control in the voicing contrast: Evidence from surgery-related apraxia
of speech.
AB - The goal of this study was to investigate the phonetic realisation of the voicing
feature in two tumour resection-related Spanish speakers with apraxia of speech.
Temporal parameters related to the phonological contrast of voicing in Spanish
have been analysed for intervocalic voiced and voiceless obstruents embedded in
isolated words and nonwords, and compared with data collected from healthy
speakers. Results indicate that in devoiced productions, where VOT values fitted
the 'voiceless stops' category, vowel duration values matched those of voiced
stops and suggested the preservation of contextual voicing cues. An attempt at
preserving a consonant/vowel duration ratio consistent with aerodynamic
predictions for voicing contrast has been observed in apraxic correct production
as well as in devoicing errors, but not in the control group, which could be
interpreted as a compensatory mechanism.
PMID- 28703649
TI - Letter to the Editor.
PMID- 28703650
TI - AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF
ENDOCRINOLOGY POSITION STATEMENT ON MENOPAUSE-2017 UPDATE.
AB - : EXECUTIVE SUMMARY This American Association of Clinical Endocrinologists
(AACE)/American College of Endocrinology (ACE) Position Statement is designed to
update the previous menopause clinical practice guidelines published in 2011 but
does not replace them. The current document reviews new clinical trials published
since then as well as new information regarding possible risks and benefits of
therapies available for the treatment of menopausal symptoms. AACE reinforces the
recommendations made in its previous guidelines and provides additional
recommendations on the basis of new data. A summary regarding this position
statement is listed below: New information available from randomized clinical
trials and epidemiologic studies reported after 2011 was critically reviewed. No
previous recommendations from the 2011 menopause clinical practice guidelines
have been reversed or changed. Newer information enhances AACE's guidance for the
use of hormone therapy in different subsets of women. Newer information helps to
support the use of various types of estrogens, selective estrogen-receptor
modulators (SERMs), and progesterone, as well as the route of delivery. Newer
information supports the previous recommendation against the use of bioidentical
hormones. The use of nonhormonal therapies for the symptomatic relief of
menopausal symptoms is supported. Newer information enhances AACE's guidance for
the use of hormone therapy in different subsets of women. Newer information helps
to support the use of various types of estrogens, SERMs, and progesterone, as
well as the route of delivery. Newer information supports the previous
recommendation against the use of bioidentical hormones. The use of nonhormonal
therapies for the symptomatic relief of menopausal symptoms is supported. New
recommendations in this position statement include: 1. RECOMMENDATION: the use of
menopausal hormone therapy in symptomatic postmenopausal women should be based on
consideration of all risk factors for cardiovascular disease, age, and time from
menopause. 2. RECOMMENDATION: the use of transdermal as compared with oral
estrogen preparations may be considered less likely to produce thrombotic risk
and perhaps the risk of stroke and coronary artery disease. 3. RECOMMENDATION:
when the use of progesterone is necessary, micronized progesterone is considered
the safer alternative. 4. RECOMMENDATION: in symptomatic menopausal women who are
at significant risk from the use of hormone replacement therapy, the use of
selective serotonin re-uptake inhibitors and possibly other nonhormonal agents
may offer significant symptom relief. 5. RECOMMENDATION: AACE does not recommend
use of bioidentical hormone therapy. 6. RECOMMENDATION: AACE fully supports the
recommendations of the Comite de l'Evolution des Pratiques en Oncologie regarding
the management of menopause in women with breast cancer. 7. RECOMMENDATION: HRT
is not recommended for the prevention of diabetes. 8. RECOMMENDATION: In women
with previously diagnosed diabetes, the use of HRT should be individualized,
taking in to account age, metabolic, and cardiovascular risk factors.
ABBREVIATIONS: AACE = American Association of Clinical Endocrinologists; ACE =
American College of Endocrinology; BMI = body mass index; CAC = coronary artery
calcification; CEE = conjugated equine estrogen; CEPO = Comite de l'Evolution des
Pratiques en Oncologie; CAD = coronary artery disease; CIMT = carotid intima
media thickness; CVD = cardiovascular disease; FDA = Food and Drug
Administration; HDL = high-density lipoprotein; HRT = hormone replacement
therapy; HT = hypertension; KEEPS = Kronos Early Estrogen Prevention Study; LDL =
low-density lipoprotein; MBS = metabolic syndrome; MPA = medroxyprogesterone
acetate; RR = relative risk; SERM = selective estrogen-receptor modulator; SSRI =
selective serotonin re-uptake inhibitor; VTE = venous thrombo-embolism; WHI =
Women's Health Initiative.
PMID- 28703651
TI - Letter to the Editor.
PMID- 28703652
TI - Letter to the Editor.
PMID- 28703653
TI - Deriving individualised /r/ targets from the acoustics of children's non-rhotic
vowels.
AB - In visual-acoustic biofeedback for rhotic errors, learners are guided to match
the third formant (F3) location to a visual target on a real-time acoustic
spectrum. As the acoustic properties of correct English /r/differ across
speakers, this study aimed to improve target selection by investigating the
validity of individualised targets derived from children's non-rhotic vowels. A
previously proposed prediction formula was adjusted using data from a child
normative sample and tested in two groups of children. Study 1 found that
predicted values were unexpectedly higher than actual F3 values in children whose
/r/ errors had been remediated. To understand this discrepancy, Study 2 applied
the formula to typically developing children and found that predicted values were
also higher than actual F3 values, suggesting that different normative data might
better represent the current samples. An updated formula is proposed, which can
be used to generate individualised targets within acoustic biofeedback
applications.
PMID- 28703655
TI - Balancing the risks and benefits of medication organizers: reply to Wang et al.
PMID- 28703656
TI - Development and Student Evaluation of an Anatomically Correct High-Fidelity Calf
Leg Model.
AB - Obstetrical chain placement requires location of specific landmarks and a certain
dexterity that must be practiced. Use of low-fidelity models may not always
provide students with a realistic experience. In this study we developed an
anatomically correct high-fidelity calf leg model that would serve as a better
teaching model for pre-clinical veterinary students than a pre-existing low
fidelity polyvinyl chloride (PVC) model. One hundred and twenty pre-clinical
veterinary students were instructed how to use obstetrical chains with a low
fidelity PVC model and the anatomically correct high-fidelity calf leg model.
After a 45-minute lab, students were surveyed on their experience with both
models. Overall students felt the anatomically correct high-fidelity calf leg
model increased accuracy in chain placement and provided more accurate landmarks,
a more realistic model, and more real-life scenario training.
PMID- 28703654
TI - Do social insects support Haig's kin theory for the evolution of genomic
imprinting?
AB - Although numerous imprinted genes have been described in several lineages, the
phenomenon of genomic imprinting presents a peculiar evolutionary problem.
Several hypotheses have been proposed to explain gene imprinting, the most
supported being Haig's kinship theory. This theory explains the observed pattern
of imprinting and the resulting phenotypes as a competition for resources between
related individuals, but despite its relevance it has not been independently
tested. Haig's theory predicts that gene imprinting should be present in eusocial
insects in many social scenarios. These lineages are therefore ideal for testing
both the theory's predictions and the mechanism of gene imprinting. Here we
review the behavioral evidence of genomic imprinting in eusocial insects, the
evidence of a mechanism for genomic imprinting and finally we evaluate recent
results showing parent of origin allele specific expression in honeybees in the
light of Haig's theory.
PMID- 28703657
TI - Examination Outcomes Following Use of Card Games for Learning Radiographic Image
Quality in Veterinary Medicine.
AB - Understanding the concepts of radiographic image quality and artifact formation
can be difficult for veterinary students. Two educational card games were
previously developed to help students learn about factors affecting contrast and
blackness as well as radiographic artifacts. Second-year veterinary students
played one of the two card games as a part of their normal studies for their
veterinary imaging course and later took the radiographic physics quiz normally
administered during the course. Performance on quiz questions related to each of
the two games was compared between students who played each respective game and
those who did not. The hypothesis was that students who played a game would
perform better on related questions than those who did not play that game. For
the contrast and blackness questions, students who played the associated game as
part of their studies performed better than those who only studied by
conventional means (mean 4.3 vs. 3.8 out of 5 points, p=.02). However, there was
no significant difference in results between groups for artifacts questions (mean
4.7 vs. 4.5 out of 5 points, p=.35). Based on these results, educational game
play can have benefits to student learning, but performance may be dependent on
specific game objectives and play mechanics.
PMID- 28703658
TI - Epigenetic silencing of miR-203 in Kazakh patients with esophageal squamous cell
carcinoma by MassARRAY spectrometry.
AB - Dysregulation of miR-203 by promoter methylation is associated with the
development of various cancers. We aimed to explore the underlying link between
promoter methylation and miR-203 expression in Kazakh esophageal squamous cell
carcinoma (ESCC). MassARRAY(r) System spectrometry was used to quantitatively
analyze the DNA methylation of 32 CpG sites within miR-203 in 99 Kazakh ESCC and
46 normal esophageal tissues (NETs) with similar population characteristics. We
conducted real-time PCR to detect miR-203 expression levels and evaluated their
association with methylation. Eleven CpG units within miR-203 promoter were
frequently hypermethylated in ESCC compared with NETs (P < 0.05). The
hypermethylation of several CpG units positively correlated with age, lower
esophagus, constrictive type of ESCC, and moderately differentiated ESCC. Given
the involvement of human papillomavirus (HPV) in etiology of ESCC was confirmed
from our previous reports, herein we found that CpG units within miR-203 in HPV16
positive ESCC are more heavily methylated. Furthermore, miR-203 expression showed
a nearly 4.5-fold decrease in ESCC than NETs (0.206 +/- 0.336 vs. 0.908 +/-
1.424, P < 0.001) and was significantly associated with lymph node metastasis (P
= 0.012). The expression of miR-203 with 11 completely hypermethylated CpG units
was approximately 6.5-fold lower than that with at least 1 unmethylated CpG unit
(P < 0.001) and especially the CpG_15.16 and CpG_31.32 with higher methylation
levels in ESCC tissues exhibited lower expression levels of miR-203, which
indicated a reverse association between miR-203 methylation and expression.
Hypermethylated miR-203 is a potential biomarker and targeted delivery of miR-203
could therefore serve as a preventive or therapeutic strategy for Kazakh ESCC.
PMID- 28703659
TI - Cost-effectiveness analysis of ocrelizumab versus subcutaneous interferon beta-1a
for the treatment of relapsing multiple sclerosis.
AB - AIM: To conduct a cost-effectiveness analysis to compare ocrelizumab vs
subcutaneous (SC) interferon beta-1a for the treatment of relapsing multiple
sclerosis (RMS). METHODS: A Markov cohort model with a 20-year horizon was
developed to compare ocrelizumab with SC interferon beta-1a from a US payer
perspective. A cohort of patients with relapsing-remitting MS (RRMS) and Expanded
Disability Status Scale (EDSS) scores of 0-6, who initiated treatment with
ocrelizumab or SC interferon beta-1a, were entered into the model. The model
considered 21 health states: EDSS 0-9 in RRMS, EDSS 0-9 in secondary-progressive
multiple sclerosis (SPMS), and death. Patients with RRMS could transition across
EDSS scores, progress to SPMS, experience relapses, or die. Transition
probabilities within RRMS while patients received ocrelizumab or SC interferon
beta-1a were based on data from the two SC interferon beta-1a-controlled Phase
III OPERA I and OPERA II trials of ocrelizumab in RMS. Transitions within RRMS
when off-treatment, RRMS-to-SPMS transitions, transitions within SPMS, and
transitions to death were based on the literature. Utilities of health states,
disutilities of relapses, costs of therapies, and medical costs associated with
health states, relapse, and adverse events were from the literature and publicly
available data sources. The model estimated per-patient total costs, incremental
cost per life year (LY) gained, and incremental cost per quality-adjusted LY
(QALY) gained. Deterministic sensitivity analyses (DSA) and probabilistic
sensitivity analysis (PSA) were conducted to evaluate the robustness of the model
results. RESULTS: Ocrelizumab was associated with a cost savings of $63,822 and
longer LYs (Delta = 0.046) and QALYs (Delta = 0.556) over a 20-year time horizon.
The results of the model were robust in the DSA and PSA. LIMITATIONS: The model
did not consider subsequent treatments and their impact on disease progression.
CONCLUSIONS: The results suggest that ocrelizumab is more cost-effective than SC
interferon beta-1a for the treatment of RMS.
PMID- 28703660
TI - Comparison of two preventive treatments for patients with recurrent miscarriages
carrying a C677T methylenetetrahydrofolate reductase mutation: 5-year experience.
AB - Objective To investigate the effect of anticoagulant treatment on pregnancy
outcomes in patients with previous recurrent miscarriages (RM) who carry a
methylenetetrahydrofolate reductase ( MTHFR) gene mutation. Methods In this
longitudinal retrospective study, patients with RM were treated during pregnancy
with either: (i) 100 mg/day aspirin and 5 mg/day folic acid (group 1); or the
same protocol plus 0.4 mg/day enoxaparin (group 2). An age-matched group of
triparous women without RM or thrombophilia was used as the control group (group
3). Results This study enrolled 246 women with RM (123 per treatment group) and
age-matched controls ( n = 117). The delivery rate was significantly lower in
group 1 than group 2 (46.3% versus 79.7%, respectively). The miscarriage rate was
significantly lower in group 2 compared with group 1 (20.3% versus 51.2%,
respectively). In the control group 3, the delivery rate was 86.3% and the
miscarriage rate was 12.8%. Conclusion Treatment with low-dose aspirin,
enoxaparin and folic acid was the most effective therapy in women with RM who
carried a C677T MTHFR mutation.
PMID- 28703661
TI - Diagnostic usefulness of laparoscopy versus exploratory laparotomy for dogs with
suspected gastrointestinal obstruction.
AB - OBJECTIVE To evaluate the feasibility of laparoscopy versus exploratory
laparotomy for the diagnosis of specific lesions in dogs with suspected
gastrointestinal obstruction. DESIGN Controlled trial. ANIMALS 16 client-owned
dogs with physical and radiographic findings consistent with gastrointestinal
obstruction. PROCEDURES Single-incision laparoscopy with intracorporeal and
extracorporeal examination of the gastrointestinal tract was performed by 1
surgeon. Immediately afterward, exploratory laparotomy was performed by a second
surgeon. Accessibility and gross appearance of organs, surgical diagnoses,
incision lengths, procedure duration, and complications were compared between
diagnostic techniques. RESULTS Mean (95% confidence interval) incision length was
4.9 cm (3.9 to 5.9 cm) for laparoscopy and 16.4 cm (14.0 to 18.7 cm) for
exploratory laparotomy. Mean (95% confidence interval) procedure duration was
36.8 minutes (31.6 to 41.2 minutes) and 12.8 minutes (11.4 to 14.3 minutes),
respectively. Diagnoses of the cause of obstruction were the same with both
methods. In 13 dogs, the laparoscopic examination was successfully completed, and
in the other 3, it was incomplete. In 4 dogs in which laparoscopy was successful,
conversion to exploratory laparotomy or considerable extension of the
laparoscopic incision would have been required to allow subsequent surgical
treatment of identified lesions. No dogs developed major complications, and minor
complication rates were similar between procedures. CONCLUSIONS AND CLINICAL
RELEVANCE Laparoscopy was feasible and clinically applicable in dogs with
suspected gastrointestinal obstruction. Careful patient selection and liberal
criteria for conversion to an open surgical approach are recommended when
laparoscopy is considered for the diagnosis of gastrointestinal lesions in dogs.
PMID- 28703662
TI - Over bagging in dairy show cows: an ethical crisis.
PMID- 28703663
TI - Anesthesia Case of the Month.
PMID- 28703665
TI - Letters to the Editor.
PMID- 28703664
TI - Diagnostic Imaging in Veterinary Dental Practice.
PMID- 28703666
TI - What Is Your Diagnosis? Ectopic thyroid carcinoma.
PMID- 28703667
TI - Surgical treatment of a paraspinal abscess with osteomyelitis and spinal cord
compression in a rabbit.
AB - CASE DESCRIPTION A 16-month-old neutered male Continental Giant rabbit (Lepus
curpaeums) was referred for evaluation of a 7-day history of acute-onset,
progressive, symmetric paraparesis. CLINICAL FINDINGS On initial examination, the
rabbit was nonambulatory, and results of neurologic examination were consistent
with a lesion affecting the T3-L3 spinal cord segments. Thoracic radiography
showed irregular widening of the left T11-12 articular process joint. Marked
dorsolateral and lateral extradural spinal cord compression with contrast
enhancement of the adjacent epaxial muscles was evident on MRI images of the
spine. TREATMENT AND OUTCOME A left-sided T11-T12 hemilaminectomy was performed,
which revealed an abnormal and hypertrophic T11-12 articular process joint and an
osteolytic lesion communicating with the vertebral canal. Copious purulent
material causing marked spinal cord compression was evident, and the surgical
site was lavaged extensively with sterile (0.9% NaCl) saline solution. Results of
aerobic, anaerobic, and enriched bacteriologic cultures of swab specimens
obtained from the surgical site were negative. Histologic analysis of biopsy
samples revealed chronic purulent osteomyelitis, myositis, and fasciitis with
necrosis, fibrosis, and dystrophic mineralization. The rabbit was discharged 48
hours after surgery. Ten weeks after surgery, the rabbit was ambulatory with mild
paraparesis. On telephone follow-up 21 months after surgery, the owners indicated
that the rabbit was healthy and expressed satisfaction with the treatment and
outcome. CLINICAL RELEVANCE Paraspinal abscess with vertebral canal involvement
should be considered as a differential diagnosis for rabbits with clinical signs
of progressive T3-L3 myelopathy. Outcome for the patient of the present report
suggested that surgical treatment including decompression and debridement can
result in a favorable long-term outcome.
PMID- 28703668
TI - ECG of the Month.
PMID- 28703669
TI - Animal Behavior Case of the Month.
PMID- 28703670
TI - Serving you; serving the AVMA; serving veterinary medicine.
PMID- 28703671
TI - Fifty years of contributions by the American Board of Veterinary Toxicology.
PMID- 28703672
TI - Randomized blinded controlled trial to assess the association between a
commercial vaccine against Moraxella bovis and the cumulative incidence of
infectious bovine keratoconjunctivitis in beef calves.
AB - OBJECTIVE To assess the association between a commercially available vaccine
against Moraxella bovis and cumulative incidence of infectious bovine
keratoconjunctivitis (IBK) from processing to weaning (primary objective) and
body weight at weaning (secondary objective). DESIGN Randomized blinded
controlled trial. ANIMALS 214 calves (>= 2 months of age) born in the spring of
2015 at an Iowa State University cow-calf research unit with no visible lesions
or scars on either eye. PROCEDURES Calves were randomly allocated to receive SC
administration of a single dose of a commercial vaccine against M bovis (112
enrolled and 110 analyzed) or saline (0.9% NaCl) solution (111 enrolled and 104
analyzed). Calves were monitored for signs of IBK from treatment to weaning, and
body weight at weaning was recorded. People involved in calf enrollment and
outcome assessment were blinded to treatment group assignment. Cumulative
incidence of IBK and weaning weight were compared between vaccinated and
unvaccinated calves; the effect measure was the risk ratio and mean difference,
respectively. RESULTS IBK was detected in 65 (59.1%) vaccinated calves and 62
(59.6%) unvaccinated calves (unadjusted risk ratio, 0.99; 95% confidence
interval, 0.79 to 1.24) during the study period. No significant difference in
weaning weights was identified between vaccinated and unvaccinated calves
(unadjusted effect size, 4.40 kg [9.68 lb]; 95% confidence interval, -3.46 to
12.25 kg [-7.61 to 26.95 lb]). CONCLUSIONS AND CLINICAL RELEVANCE Results
suggested that the commercially available M bovis vaccine was not effective in
reducing the cumulative incidence of IBK or increasing weaning weight in beef
calves.
PMID- 28703673
TI - In This Issue * August 1, 2017.
PMID- 28703674
TI - What Is Your Neurologic Diagnosis? Squamous cell carcinomas.
PMID- 28703675
TI - Pathology in Practice. Trichofolliculoma (ruptured) and secondary
pyogranulomatous furunculosis in a rock hyrax.
PMID- 28703676
TI - Evaluation of learning curves for ovariohysterectomy of dogs and cats and
castration of dogs.
AB - OBJECTIVE To define learning curves for fourth-year veterinary students
performing ovariohysterectomy procedures in dogs and cats and castration in dogs.
DESIGN Retrospective study. SAMPLE 3,196 ovariohysterectomies or castrations
performed in dogs and cats by 88 veterinary students during a spay-neuter surgery
and animal shelter rotation (n = 3,056) or by 1 experienced general practitioner
(n = 140). PROCEDURES Data collected from medical records included patient
signalment, type and duration of procedure, and sequence (by date and time) of
the procedure within a list of procedures of the same type generated for each
student. For each procedure type, geometric mean surgery time and 95% confidence
intervals were determined for each number of surgeries completed by >= 10
students. Median surgery times for the same procedure types were determined for
the experienced practitioner. The learning curve for each procedure was modeled
with nonlinear (3-factor exponential equation with a nonzero asymptote) and
linear regression. For each procedure, the asymptote (optimal surgery time) for
students was compared with the experienced practitioner's median surgery time.
RESULTS 2,945 surgeries (mean, 33/student) performed by >= 10 students were
analyzed. Surgery time decreased in a nonlinear manner as student experience
increased for castration of adult or pediatric dogs and ovariohysterectomy of
pediatric dogs and adult or pediatric cats. Surgery time decreased in a linear
manner as experience increased for ovariohysterectomy of adult dogs. CONCLUSIONS
AND CLINICAL RELEVANCE To the authors' knowledge, this was the first study to map
surgery times for common surgical procedures consecutively performed by
veterinary students. Results clearly indicated the value of repetition to improve
surgical skills (as measured by surgery time) during a 3-week period.
PMID- 28703677
TI - Single oblique osteotomy for correction of antebrachial angular and torsional
deformities in a dog.
AB - CASE DESCRIPTION A 9-month-old 4.6-kg (10.1-lb) spayed female Shih Tzu was
examined for a 4-week history of left forelimb lameness. CLINICAL FINDINGS
Moderate left forelimb lameness was present when weight bearing, accompanied by
buckling of the left carpal joint and moderate signs of pain with hyperextension
of the elbow joint. A 32 degrees angular deformity of the left radius in a 45
degrees craniomedial oblique plane (equivalent to 23 degrees valgus and 23
degrees procurvatum) and a 55 degrees external torsional deformity were
measured on 3-D reconstructed CT images. Humeroulnar incongruity of the left
elbow joint was also evident. Single oblique osteotomy (SOO) and dynamic proximal
ulnar osteotomy were recommended. TREATMENT AND OUTCOME Creation of a 3-D printed
bone model from reconstructed CT images aided surgical planning. The SOO was
located 45 degrees medial to the sagittal plane of the left radius at the level
of the center of rotation of angulation. The SOO was oriented 32 degrees
distolaterally from the transverse plane of the radius and traversed the left
ulna. The bones were rotated along the osteotomy into grossly proper alignment
and stabilized with a plate and bone screws. Dynamic proximal ulnar osteotomy was
then performed. Six months after surgery, radiographs showed remodeling at the
SOO site and the lameness had resolved. The owners expressed satisfaction with
the outcome. CLINICAL RELEVANCE In dogs with angular and torsional long bone
deformities, SOO may be a viable alternative to wedge osteotomies. The SOO
simultaneously addressed angular and torsional deformities without bone loss and
provided rigid internal fixation.
PMID- 28703678
TI - Pathology in Practice. Nasal adenocarcinoma with rostral cerebral invasion in a
cat.
PMID- 28703680
TI - Ultrasonographic and computed tomographic characterization and localization of
suspected mechanical gastrointestinal obstruction in dogs.
AB - OBJECTIVE To evaluate the usefulness of noncontrast abdominal CT and abdominal
ultrasonography for the detection of mechanical gastrointestinal obstruction in
dogs and compare intestinal diameter ratios between dogs with and without
obstruction. DESIGN Controlled trial. ANIMALS 16 client-owned dogs with physical
and radiographic findings consistent with mechanical gastrointestinal
obstruction. PROCEDURES Abdominal ultrasonography and CT were performed for all
dogs, followed by laparoscopy and exploratory laparotomy. Time required for image
acquisition and presence and location of gastrointestinal obstruction were
assessed with both imaging modalities. Findings were compared with those of
exploratory surgery. Maximum and minimum intestinal diameters were recorded on CT
scans; values were converted to a ratio and compared between dogs with and
without obstruction. RESULTS Results of abdominal CT and exploratory surgery for
the diagnosis of mechanical obstruction agreed for all 16 dogs; 10 dogs had
complete obstruction, 3 had partial obstruction, and 3 had no obstruction. In 1
dog with functional ileus, abdominal ultrasonography resulted in an incorrect
diagnosis of mechanical obstruction. Median (interquartile range) image
acquisition time for abdominal CT (2.5 minutes [2.0 to 3.8 minutes]) was markedly
and significantly shorter than that for ultrasonography (26.0 minutes [22.0 to
35.8 minutes]). In both dorsal and transverse CT planes, dogs with
gastrointestinal obstruction (partial or complete) had significantly larger
intestinal diameter ratios than dogs without obstruction. CONCLUSIONS AND
CLINICAL RELEVANCE Abdominal CT was feasible, rapid, and accurate for the
diagnosis of mechanical obstruction in dogs with clinical signs and physical
examination findings consistent with partial or complete gastrointestinal
obstruction.
PMID- 28703681
TI - Activation of gene expression by histone deubiquitinase OTLD1.
AB - One of the main mechanisms of epigenetic control is post translational
modification of histones, and one of the relatively less characterized, yet
functionally important histone modifications is monoubiquitylation, which is
reversed by histone deubiquitinases. In Arabidopsis, only two of such enzymes are
known to date. One of them, OTLD1, deubiquitylates histone 2B and functions as a
transcriptional repressor. But, could the same deubiquitinase act both as a
repressor and an activator? Here, we addressed this question. Using gain-of
function and loss-of-function Arabidopsis alleles, we showed that OTLD1 can
promote expression of a target gene. This transcriptional activation activity of
OTLD1 involves occupation of the target chromatin by this enzyme,
deubiquitination of monoubiquitylated H2B within the occupied regions, and
formation of the euchromatic histone acetylation and methylation marks. Thus,
OTLD1 can play a dual role in transcriptional repression and activation of its
target genes. In these reactions, H2B ubiquitylation acts as both a repressive
and an active mark whereas OTLD1 association with and deubiquitylation of the
target chromatin may represent the key juncture between two opposing effects of
this enzyme on gene expression.
PMID- 28703682
TI - A MBD-seq protocol for large-scale methylome-wide studies with (very) low amounts
of DNA.
AB - We recently showed that, after optimization, our methyl-CpG binding domain
sequencing (MBD-seq) application approximates the methylome-wide coverage
obtained with whole-genome bisulfite sequencing (WGB-seq), but at a cost that
enables adequately powered large-scale association studies. A prior drawback of
MBD-seq is the relatively large amount of genomic DNA (ideally >1 ug) required to
obtain high-quality data. Biomaterials are typically expensive to collect,
provide a finite amount of DNA, and may simply not yield sufficient starting
material. The ability to use low amounts of DNA will increase the breadth and
number of studies that can be conducted. Therefore, we further optimized the
enrichment step. With this low starting material protocol, MBD-seq performed
equally well, or better, than the protocol requiring ample starting material (>1
ug). Using only 15 ng of DNA as input, there is minimal loss in data quality,
achieving 93% of the coverage of WGB-seq (with standard amounts of input DNA) at
similar false/positive rates. Furthermore, across a large number of genomic
features, the MBD-seq methylation profiles closely tracked those observed for WGB
seq with even slightly larger effect sizes. This suggests that MBD-seq provides
similar information about the methylome and classifies methylation status
somewhat more accurately. Performance decreases with <15 ng DNA as starting
material but, even with as little as 5 ng, MBD-seq still achieves 90% of the
coverage of WGB-seq with comparable genome-wide methylation profiles. Thus, the
proposed protocol is an attractive option for adequately powered and cost
effective methylome-wide investigations using (very) low amounts of DNA.
PMID- 28703683
TI - Integrated process development-a robust, rapid method for inclusion body
harvesting and processing at the microscale level.
AB - Escherichia coli stores large amounts of highly pure product within inclusion
bodies (IBs). To take advantage of this beneficial feature, after cell
disintegration, the first step to optimal product recovery is efficient IB
preparation. This step is also important in evaluating upstream optimization and
process development, due to the potential impact of bioprocessing conditions on
product quality and on the nanoscale properties of IBs. Proper IB preparation is
often neglected, due to laboratory-scale methods requiring large amounts of
materials and labor. Miniaturization and parallelization can accelerate analyses
of individual processing steps and provide a deeper understanding of up- and
downstream processing interdependencies. Consequently, reproducible, predictive
microscale methods are in demand. In the present study, we complemented a
recently established high-throughput cell disruption method with a microscale
method for preparing purified IBs. This preparation provided results comparable
to laboratory-scale IB processing, regarding impurity depletion, and product
loss. Furthermore, with this method, we performed a "design of experiments" study
to demonstrate the influence of fermentation conditions on the performance of
subsequent downstream steps and product quality. We showed that this approach
provided a 300-fold reduction in material consumption for each fermentation
condition and a 24-fold reduction in processing time for 24 samples.
PMID- 28703684
TI - Development of antifungal therapies using nanomaterials.
AB - The number and diversity of chemical structures currently available as
antibacterial drugs is much higher compared with the number of active substances
in relation to pathogenic fungi. In this review we focus on nanotechnology
approaches, which offer promising strategies to create nanoagents that possess
broad-spectrum antifungal activity and might overcome mechanisms of antibiotic
resistance. Special attention was given to magnetic nanoparticles and their
ability to restrict fungal growth directly, which depends on surface chemistry
and pathogen strains. We speculate that future developments of new antifungal
methods will take advantage of the current knowledge of using of magnetic
nanomaterials as anticancer agents based on their ability to induce hyperthermia
and enhance photosensitizing processes.
PMID- 28703685
TI - A Method for Gray-Scale Imaging of Blood Flow Using High-Frequency Ultrasound.
AB - This paper presents a new method that complements current techniques available in
the high-frequency blood imaging field. A comprehensive scattering model was
established to determine the feasibility and frequency range of the blood flow
imaging of superficial organs and tissues using high-frequency ultrasound. The
transmitting and receiving modes and an algorithm were designed to obtain blood
flow information based on differentiation between tissues and blood flow. The
system was created and tested first with a model that simulates blood flow and
was then used on human tissue. A fine-scale image of a blood vessel could be
obtained with this system. Moreover, this method can obtain weak blood flow
signal using single pulse rather than the traditional pulse-code method and
maintains a high resolution that can be matched to high-frequency structural
imaging. This study provides a reliable method for further applications related
to diagnoses of superficial organs.
PMID- 28703686
TI - Prevalence and associated demographic characteristics of exposure to multiple
metals and their species in human populations: The United States NHANES, 2007
2012.
AB - Lead (Pb), cadmium (Cd), mercury (Hg), and arsenic (As) are among the top 10
pollutants of global health concern. Studies have shown that exposures to these
metals produce severe adverse effects. However, the mechanisms underlying these
effects, particularly joint toxicities, are poorly understood in humans. The
objective of this investigation was to identify and characterize prevalent
combinations of these metals and their species in the U.S. NHANES population to
provide background data for future studies of potential metal interactions.
Exposure was defined as urine or blood levels >= medians of the NHANES 2007-2012
participants >=6 years (n = 7408). Adjusted-odds ratios (adj-OR) and 95%
confidence intervals were determined for covariates (age, gender, and
race/ethnicity, cotinine and body mass index). Species-specific analysis was also
conducted for As and Hg including iAs (urinary arsenous acid and/or arsenic
acid), met-iAs (urinary monomethylarsonic acid and/or dimethylarsinic acid), and
oHg (blood methyl-mercury and/or ethyl-mercury). For combinations of As and Hg
species, age- and gender-specific prevalence was determined among NHANES 2011
2012 participants (n = 2342). Data showed that approximately 49.3% of the
population contained a combination of three or more metals. The most prevalent
unique specific combinations were Pb/Cd/Hg/As, Pb/Cd/Hg, and Pb/Cd. Age was
consistently associated with these combinations: adj-ORs ranged from 10.9 (Pb/Cd)
to 11.2 (Pb/Cd/Hg/As). Race/ethnicity was significant for Pb/Cd/Hg/As. Among
women of reproductive age, frequency of oHg/iAs/met-iAS and oHg/met-iAs was 22.9
and 40.3%, respectively. These findings may help prioritize efforts to assess
joint toxicities and their impact on public health.
PMID- 28703687
TI - Our panel of experts highlight the most important research articles across the
spectrum of topics relevant to the field of regenerative medicine.
PMID- 28703688
TI - Activity-based funding in mental health: a disastrous path.
AB - OBJECTIVES: On the basis of the experience of the Netherlands, this critical
commentary will argue why activity-based funding (ABF) in mental health care is a
disastrous path that Australia should not take. CONCLUSIONS: ABF leads to an
exponential growth in health care spending as it encourages diagnostic inflation
and overproductivity. It also leads to fraud and an increased bureaucracy that
goes hand in hand with demoralisation among health workers. And finally, the
increasing treatment claims leads to the reintroduction of productivity
limitations, waiting lists and ultimately austerity measures in order to halt the
untamed growth of spending.
PMID- 28703689
TI - Supervision: 'a random bag of arrangements'? Perspectives from psychiatrists on
how to improve clinical teaching.
AB - OBJECTIVE: The aim of this study was to explore psychiatrists' perspectives on
how clinical teaching and supervision can be improved in postgraduate psychiatric
training. METHOD: All New Zealand members of the Royal Australian and New Zealand
College of Psychiatrists (fellows: n=367; affiliates: n=167) were invited to
participate in an online survey that collected responses to two open-ended
questions. The responses were then analysed qualitatively. RESULTS: A total of
27% psychiatrists responded. Two major themes emerged: supervisor competencies
and the workplace educational environment, with subthemes of supervisor training,
feedback and culture change. CONCLUSIONS: Suggestions to improve clinical
teaching and supervision included defining supervisor teaching competencies,
instituting evidence-based faculty development, a feedback structure and
strengthening leadership support for workplace-based education.
PMID- 28703690
TI - What's to be done when 'foul whisp rings are abroad'? Gossip and rumour in health
organisations.
AB - OBJECTIVES: This article explores the relevance of gossip and rumour to health
organisations and presents what limited empirical research is available specific
to the management of gossip and rumour in health organisations. CONCLUSION: The
concept of a sentinel function for gossip and rumour in health organisations is
proposed as a topic worthy of further research.
PMID- 28703691
TI - Characteristics and outcomes of patients with drug overdose requiring admission
to Intensive Care Unit.
AB - OBJECTIVE: Approximately 20% of patients admitted to hospital with drug overdose
will require intensive care unit (ICU) admission. An understanding of the
characteristics of these patients may assist with their management and identify
those patients at risk of multiple hospital presentations due to drug overdose.
Our aim was to examine the characteristics of patients admitted to ICU following
drug overdoses and identify the predictors of multiple hospital presentations due
to drug overdose. METHODS: Patients admitted to a metropolitan ICU over a three
year period following drug overdoses were identified using ICU patient databases,
and their medical records. RESULTS: There were 254 admissions due to drug
overdoses. The majority of overdoses were intentional (82.7%) and included
multiple agents (68.1%). Two-thirds of patients had psychiatric diagnosis, and
54% had documented history of substance use disorders. In-hospital mortality was
2.8%. Over half of patients admitted had documented history of prior hospital
presentation due to overdoses. Personality disorder and schizophrenia were
independent predictors of multiple hospital presentations due to overdoses.
CONCLUSION: Personality disorders or schizophrenia were independent predictors of
patients with multiple overdose presentations. Preventative strategies focusing
on these patients may reduce the incidence of their hospital presentations and
ICU admissions.
PMID- 28703692
TI - Publish or perish: Dr Victor Webster and cardiazol treatment in Western
Australia, 1937-1938.
AB - OBJECTIVE: To examine the role of Dr Victor Henry Webster (1905-1980) in the
introduction of cardiazol therapy to Western Australia in November 1937. METHOD:
A range of primary and secondary sources were consulted. RESULTS: Webster
experimented with cardiazol treatment at Heathcote Reception Home, and published
his findings in April 1938, at the same time as Ellery and Lear, but was not able
to publish his results in a nationally-recognised journal. As a result, his
contribution to early cardiazol treatment in Australia has been largely
forgotten. CONCLUSIONS: Webster made a genuine contribution to the introduction
of cardiazol treatment in Australia, and his story illustrates the need to
publish early findings of new physical therapies.
PMID- 28703693
TI - Women and Aging, edited by Varda Muhlbauer, Joan C. Chrisler, and Florence L.
Denmark.
PMID- 28703694
TI - When Is Higher Neuroticism Protective Against Death? Findings From UK Biobank.
AB - We examined the association between neuroticism and mortality in a sample of
321,456 people from UK Biobank and explored the influence of self-rated health on
this relationship. After adjustment for age and sex, a 1- SD increment in
neuroticism was associated with a 6% increase in all-cause mortality (hazard
ratio = 1.06, 95% confidence interval = [1.03, 1.09]). After adjustment for other
covariates, and, in particular, self-rated health, higher neuroticism was
associated with an 8% reduction in all-cause mortality (hazard ratio = 0.92, 95%
confidence interval = [0.89, 0.95]), as well as with reductions in mortality from
cancer, cardiovascular disease, and respiratory disease, but not external causes.
Further analyses revealed that higher neuroticism was associated with lower
mortality only in those people with fair or poor self-rated health, and that
higher scores on a facet of neuroticism related to worry and vulnerability were
associated with lower mortality. Research into associations between personality
facets and mortality may elucidate mechanisms underlying neuroticism's covert
protection against death.
PMID- 28703695
TI - The decellularized extracellular matrix in regenerative medicine.
PMID- 28703696
TI - Palliative care service use by older people: Time trends from a mortality follow
back study between 2005 and 2014.
AB - BACKGROUND: The need for increased use and timely initiation of palliative care
for all people, not just those who die with cancer, has been advocated worldwide
over the past decade. AIM: To investigate whether there has been a time trend in
the use of palliative care services and the timing of their initiation for older
people. DESIGN: Mortality follow-back survey among general practitioners in a
nationally representative Sentinel Network in 2005-2010, 2013 and 2014 in
Belgium. SETTING/PARTICIPANTS: Of all their patients who died non-suddenly aged
65+ years, general practitioners reported sociodemographic and clinical data, use
of any of the palliative care services available in Belgium and when the first of
these services was initiated. RESULTS: General practitioners identified 5344
deaths. Overall, palliative care service use increased from 39% in 2005 to 63% in
2014 ( p < 0.001). The use of a reference person for palliative care in a care
home increased from 12% to 26% ( p < 0.001) and of a palliative homecare team
from 14% to 17.5% ( p < 0.01), but hospital-based palliative care services did
not increase. Controlling for sociodemographic characteristics, no differences
were obtained over time in the proportion of cancer/non-cancer patients for whom
they provided care. The timing of initiation of palliative care services remained
unchanged at a median of 15 days before death. CONCLUSION: Palliative care
service use has increased mostly in care homes, possibly as a result of policy
changes, while hospital-based palliative care services lag behind. Contrary to
recommendations, access for non-cancer patients may remain difficult and
palliative care is often initiated late in the disease trajectory.
PMID- 28703697
TI - Detection of chronic wasting disease prion seeding activity in deer and elk feces
by real-time quaking-induced conversion.
AB - Chronic wasting disease (CWD) is an emergent prion disease affecting cervid
species in North America, Canada, South Korea, and recently, Norway. Detection of
CWD has been advanced by techniques that rely on amplification of low levels of
prion amyloid to a detectable level. However, the increased sensitivity of
amplification assays is often compromised by inhibitors and/or activators in
complex biologic samples including body fluids, excreta, or the environment.
Here, we adapt real-time quaking-induced conversion conditions to specifically
detect CWD prions in fecal samples from both experimentally infected deer and
naturally infected elk and estimate environmental contamination. The results have
application to detection, surveillance and management of CWD, and potentially to
other protein-misfolding diseases.
PMID- 28703698
TI - Recovery of the Zika virus through an in vitro ligation approach.
AB - In this study, an in vitro ligation method was developed to assemble a full
length infectious cDNA clone of the Zika virus (ZIKV). Four contiguous cDNA
subclones covering the complete ZIKV genome were constructed with unique BglI
restriction sites at the ends of each fragment. The BglI restriction sites only
allow in vitro ligation to happen between interconnecting restriction sites from
adjacent cDNA fragments, resulting in an intact full-length cDNA of ZIKV. RNA
transcripts derived from the full-length cDNA were infectious. The recombinant
virus replicated as efficiently as the wild-type virus with similar growth
kinetics and plaque morphologies in Vero and C6/36 cells. Both viruses were
inhibited by NITD008 treatment. This in vitro ligation method will facilitate
manipulation of the viral genome through genetic modifications of four separated
subclones of ZIKV for the rapid and rational development of candidate vaccines
and viral replication study.
PMID- 28703699
TI - A high prevalence of beak and feather disease virus in non-psittacine Australian
birds.
AB - PURPOSE: Beak and feather disease virus (BFDV) is a circovirus and the cause of
psittacine beak and feather disease (PBFD). This disease is characterized by
feather and beak deformities and is a recognized threat to endangered
Psittaciformes (parrots and cockatoos). The role that non-psittacine birds may
play as reservoirs of infection is unclear. This study aimed to begin addressing
this gap in our knowledge of PBFD. METHODOLOGY: Liver samples were collected from
birds presented to the Australian Wildlife Health Centre at Zoos Victoria's
Healesville Sanctuary for veterinary care between December 2014 and December
2015, and tested for BFDV DNA using polymerase chain reaction coupled with
sequencing and phylogenetic analyses.Results/Key findings. Overall BFDV was
detected in 38.1 % of 210 birds. BFDV was detected at high prevalence (56.2 %) in
psittacine birds, in the majority of cases without any observed clinical signs of
PBFD. We also found that BFDV was more common in non-psittacine species than
previously recognized, with BFDV detected at 20.0 % prevalence in the non
psittacine birds tested, including species with no clear ecological association
with psittacines, and without showing any detectable clinical signs of BFDV
infection. CONCLUSION: Further research to determine the infectivity and
transmissibility of BFDV in non-psittacine species is indicated. Until such work
is undertaken the findings from this study suggest that every bird should be
considered a potential carrier of BFDV, regardless of species and clinical
presentation. Veterinary clinics and wildlife rehabilitation facilities caring
for birds that are susceptible to PBFD should reconsider biosecurity protocols
aimed at controlling BFDV.
PMID- 28703700
TI - Comparative study of isolates from community-acquired and catheter-associated
urinary tract infections with reference to biofilm-producing property, antibiotic
sensitivity and multi-drug resistance.
AB - PURPOSE: Urinary tract infection (UTI) can be community-acquired (Com-UTI) or
catheter-associated (CAUTI) and may be associated with biofilm-producing
organisms. A comparative analysis of biofilm-producing property (BPP), antibiotic
sensitivity and multi-drug resistance (MDR) and their relation with the BPP of
isolates from Com-UTI and CAUTI has not yet been performed and necessitated this
study. METHODOLOGY: OBJECTIVES: (1) isolation of bacteria from CAUTI and Com-UTI
and identification of their BPP, antibiotic-sensitivity and MDR status; (2)
comparison of the isolates from CAUTI and Com-UTI as regards BPP, MDR status and
their relation with BPP. METHOD: isolates from 100 cases each of Com-UTI and
CAUTI were subjected to Congo redagar (CRA) and Safranin tube tests. Antibiotic
susceptibility was investigated using the disc diffusion method. Both groups were
compared regarding BPP, drug sensitivity and MDR status. Statistical analyses
were performed using chi2 and Fisher's exact tests. RESULTS: 76.19 % of isolates
from Com-UTI and 60.72 % from CAUTI had BPP (P=0.0252; significant). The Safranin
tube test detected more isolates with BPP than the CRA test. MDR is greater in
CAUTI than Com-UTI (83.33 % versus 64.76 %; P=0.0039; significant). MDR is
greater in isolates with BPP in both Com-UTI and CAUTI (76.47 and 62.35 %; non
significant). CONCLUSIONS: BPP was found in both Com-UTI and CAUTI. When used
together, the Safranin tube test and the CRA test increased the sensitivity of
detecting BPP. MDR was higher in CAUTI than Com-UTI. MDR and BPP are not
interrelated or associated, especially in settings where it is not certain that
isolates were obtained from a well-formed biofilm. However, this does not rule
out a higher incidence or prevalence of MDR in isolates with BPP taken directly
from the biofilms.
PMID- 28703701
TI - Mutations in MmpL3 alter membrane potential, hydrophobicity and antibiotic
susceptibility in Mycobacterium smegmatis.
AB - MmpL3 is a promising target for novel anti-tubercular agents, with numerous
compound series identified as MmpL3 inhibitors. Despite this, there is an
incomplete understanding of MmpL3 function. Here we show that Mycobacterium
smegmatis MmpL3 mutant strains had an altered cell wall hydrophobicity, disrupted
membrane potential and growth defects in liquid media. Compensatory mutations
that restored normal growth also returned membrane potential to wild-type. M.
smegmatis MmpL3 mutant strains were resistant to two anti-tubercular agents,
SQ109 and AU1235, but were more sensitive to rifampicin, erythromycin and
ampicillin. Exposure of M. smegmatis to AU1235 affected the cell wall composition
and increased the potency of rifampicin. However, MmpL3 mutants did not prevent
the dissipation of membrane potential following exposure to SQ109. These results
demonstrate that in M. smegmatis, MmpL3 contributes to a number of important
phenotypes such as membrane potential, cell wall composition, antibiotic
susceptibility and fitness.
PMID- 28703702
TI - Cancers attributable to excess body weight in Canada in 2010.
AB - INTRODUCTION: Excess body weight (body mass index [BMI] >= 25.00 kg/m2) is an
established risk factor for diabetes, hypertension and cardiovascular disease,
but its relationship to cancer is lesser-known. This study used population
attributable fractions (PAFs) to estimate the cancer burden attributable to
excess body weight in Canadian adults (aged 25+ years) in 2010. METHODS: We
estimated PAFs using relative risk (RR) estimates from the World Cancer Research
Fund International Continuous Update Project, BMI-based estimates of overweight
(25.00 kg/m2-29.99 kg/m2) and obesity (30.00+ kg/m2) from the 2000-2001 Canadian
Community Health Survey, and cancer case counts from the Canadian Cancer
Registry. PAFs were based on BMI corrected for the bias in self-reported height
and weight. RESULTS: In Canada in 2010, an estimated 9645 cancer cases were
attributable to excess body weight, representing 5.7% of all cancer cases (males
4.9%, females 6.5%). When limiting the analysis to types of cancer associated
with high BMI, the PAF increased to 14.9% (males 17.5%, females 13.3%). Types of
cancer with the highest PAFs were esophageal adenocarcinoma (42.2%), kidney
(25.4%), gastric cardia (20.7%), liver (20.5%), colon (20.5%) and gallbladder
(20.2%) for males, and esophageal adenocarcinoma (36.1%), uterus (35.2%),
gallbladder (23.7%) and kidney (23.0%) for females. Types of cancer with the
greatest number of attributable cases were colon (1445), kidney (780) and
advanced prostate (515) for males, and uterus (1825), postmenopausal breast
(1765) and colon (675) for females. Irrespective of sex or type of cancer, PAFs
were highest in the Prairies (except Alberta) and the Atlantic region and lowest
in British Columbia and Quebec. CONCLUSION: The cancer burden attributable to
excess body weight is substantial and will continue to rise in the near future
because of the rising prevalence of overweight and obesity in Canada.
PMID- 28703703
TI - Estimating multimorbidity prevalence with the Canadian Chronic Disease
Surveillance System.
AB - INTRODUCTION: The Public Health Agency of Canada's Canadian Chronic Disease
Surveillance System (CCDSS) uses a validated, standardized methodology to
estimate prevalence of individual chronic diseases, such as diabetes. Expansion
of the CCDSS for surveillance of multimorbidity, the co-occurrence of two or more
chronic diseases, could better inform health promotion and disease prevention.
The objective of this study was to assess the feasibility of using the CCDSS to
estimate multimorbidity prevalence. METHODS: We used administrative health data
from seven provinces and three territories and five validated chronic conditions
(i.e. cardiovascular disease, respiratory disease, mental illness, hypertension
and diabetes) to estimate multimorbidity prevalence. We produced age-standardized
(using Canada's 1991 population) and age-specific estimates for two
multimorbidity definitions: (1) two or more conditions, and (2) three or more
conditions from the five validated conditions, by sex, fiscal year and geography.
RESULTS: Among Canadians aged 40 years and over in the fiscal year 2011/12, the
prevalence of two or more and three or more chronic conditions was 26.5% and
10.2%, respectively, which is comparable to other estimates based on
administrative health data. The increase in multimorbidity prevalence with
increasing age was similar across provinces. The difference in prevalence for
males and females varied by province and territory. We observed substantial
variation in estimates over time. Results were consistent for the two definitions
of multimorbidity. CONCLUSION: The CCDSS methodology can produce comparative
estimates of multimorbidity prevalence across provinces and territories, but
there are challenges in using it to estimate temporal trends. Further expansion
of the CCDSS in the number and breadth of validated case definitions will improve
the accuracy of multimorbidity surveillance for the Canadian population.
PMID- 28703704
TI - Commentary - Is the future of "population/public health" in Canada united or
divided? Reflections from within the field.
AB - INTRODUCTION: "Are population and public health truly a unified field, or is
population health simply attaching itself to public health as a means of gaining
credibility?" This commentary was prompted by the above question, which was asked
during K. L.'s PhD candidacy exam. In response, K. L. cited recent developments
in the field to support her conviction that population and public health (PPH)
existed positively as a unified discipline. However, through conversations that
ensued over the subsequent weeks and months, we concluded that this issue goes
deeper than the existence of departments and organizations labelled "population
and public health," and may benefit from debate and discussion, particularly for
the incoming generation of PPH scholars. In this commentary, we argue that (1)
the PPH label at times implies a coherence of ideas, values and priorities that
may not be present; (2) it is important and timely to work towards a more unified
PPH; and (3) both challenges to and opportunities for a more unified PPH exist,
which we illustrate using the broad areas of research funding, the public health
workforce and PPH ethics.
PMID- 28703705
TI - Epidemiology of human infections with highly pathogenic avian influenza A(H7N9)
virus in Guangdong, 2016 to 2017.
AB - We describe the epidemiology of highly pathogenic avian influenza (HPAI) A(H7N9)
based on poultry market environmental surveillance and laboratory-confirmed human
cases (n = 9) in Guangdong, China. We also compare the epidemiology between human
cases of high- and low-pathogenic avian influenza A(H7N9) (n = 51) in Guangdong.
Case fatality and severity were similar. Touching sick or dead poultry was the
most important risk factor for HPAI A(H7N9) infections and should be highlighted
for the control of future influenza A(H7N9) epidemics.
PMID- 28703707
TI - Pathotyping and antibiotic resistance of porcine enterovirulent Escherichia coli
strains from Switzerland (2014-2015).
AB - INTRODUCTION: A total of 131 porcine E. coli were isolated in 2014 and 2015 from
the gut of 115 pigs raised in Switzerland and suffering from diarrhea. The
isolates were tested for antibiotic resistance, serotypes, virulence factors and
genetic diversity. Serotypes were assigned by agglutination tests and virulence
genes were identified by polymerase chain reaction (PCR). Antibiotic resistance
profile was determined by the measurement of the MIC of 14 antibiotics and by the
detection of the corresponding genes using microarray and PCR approaches. Genetic
diversity was determined by repetitive palindromic PCR (rep- PCR) revealing a
heterogenous population. Half of the E. coli isolates possessing virulence
factors could not be assigned to any of the 19 serotypes tested, but contained
toxins and adhesins similarly to the sero-typable E. coli isolates. The most
prevalent E. coli serotypes found were K88ac (18%), O139:K82 (6%), O141:K85ac
(5%), O108:K'V189' (5%), O119:K'V113' (3%) and O157:K'V17' (2%). The combination
of toxins EAST-1, STb and LT-I and adhesin F4 characterizing ETEC was the most
frequent. The shigatoxin Stx2e (STEC) and intimin Eae (EPEC) were also detected,
but less frequently. Seventy percent of the isolates were resistant to at least
one antibiotic and 29% were resistant to more than 3 antibiotics. Isolates
exhibited resistance to tetracycline (50%) associated to resistance genes tet(A),
tet(B) and tet(C), sulfamethoxazole (49%) [sul1, sul2 and sul3], trimethoprim
(34%) [dfr], nalidixic acid (29%), ampicillin (26%) [blaTEM-1], gentamicin (17%)
[aac(3) -IIc, aac(3) -IVa and aac(3) -VIa], chloramphenicol (17%) [catAI and
catAIII], and ciprofloxacin (8%) [mutations in GyrA (S83L) and ParC (S80I)]. All
isolates were susceptible to 3rd generation cephalosporins, carbapenems, colistin
and tigecycline. Pathogenic E. coli isolates from pigs in Switzerland could
frequently not be assigned to a known serotype even if they contained diarrhea
causing virulence factors. They also harbor resistance mechanisms conferring
resistance to antibiotics which are commonly used in pig husbandry, except for
colistin. A careful identification of the causative agent and antibiotic
susceptibility testing is highly recommended for targeted therapy and prudent use
of antibiotics.
PMID- 28703706
TI - Dopamine neuron dependent behaviors mediated by glutamate cotransmission.
AB - Dopamine neurons in the ventral tegmental area use glutamate as a cotransmitter.
To elucidate the behavioral role of the cotransmission, we targeted the glutamate
recycling enzyme glutaminase (gene Gls1). In mice with a dopamine transporter
(Slc6a3)-driven conditional heterozygous (cHET) reduction of Gls1 in their
dopamine neurons, dopamine neuron survival and transmission were unaffected,
while glutamate cotransmission at phasic firing frequencies was reduced, enabling
a selective focus on the cotransmission. The mice showed normal emotional and
motor behaviors, and an unaffected response to acute amphetamine. Strikingly,
amphetamine sensitization was reduced and latent inhibition potentiated. These
behavioral effects, also seen in global GLS1 HETs with a schizophrenia resilience
phenotype, were not seen in mice with an Emx1-driven forebrain reduction
affecting most brain glutamatergic neurons. Thus, a reduction in dopamine neuron
glutamate cotransmission appears to mediate significant components of the GLS1
HET schizophrenia resilience phenotype, and glutamate cotransmission appears to
be important in attribution of motivational salience.
PMID- 28703708
TI - [Calculation of therapeutic intensity for pigs treated using medicated feed].
AB - INTRODUCTION: The correct oral treatment of pigs in groups is a demanding
procedure. Prescriptions of medicated feed for groups larger than 20 pigs have to
be made on official forms submitted to veterinary authorities. In this work, we
evaluated 1'126 such forms for the years 2010-2011 to calculate the therapeutic
intensity for piglets and fatteners at farm level in the canton of Lucerne. This
analysis shows that essential data were often difficult to obtain and that the
provided information did not always allow for plausible intensity calculations.
In total, 654 and 424 kg of antimicrobials were prescribed during the 2 years
under investigation. For the years 2010 and 2011, the calculated median
intensities were 43.5 and 32.5 treated animals per 1'000 individuals per day
(PIDvet) for piglets and 75.9 and 64.8 for fatteners. PIDvet for the whole
populations of piglets and fatteners treated with medicated feed delivered from
feed mills were 37.51 resp. 84.44 in the year 2011.
PMID- 28703709
TI - [Chromosomal aberrations in a subfertile cotton-top tamarin].
AB - INTRODUCTION: The present case report describes a female cotton-top tamarin which
was taken over by the Zoo Basel to form a new breeding pair. The animal
demonstrated increased marking behavior without any obvious medical reasons,
dominant behavior, failure to become pregnant and its external genitals were
ambiguous. A disorder of the sexual development (DSD) was suspected by the zoo
veterinarians and in a first step, the chromosomes of the monkey were analyzed.
Six cell lines with different karyotypes were observed. The two most frequent
cell lines had a 46,XX or a 46,XY karyotype which are normal chromosome
complements of female and male cotton-top tamarins, respectively. The other much
less frequent cell lines showed numerical aberrations with and without a marker
chromosome. Specific biological features of the Callitrichidae, such as natural
twinning and genetic chimerism impeded the clarification of the pathogenesis and
prevented a reliable prognosis on the fertility of the cotton-top tamarin.
PMID- 28703710
TI - Functionalization of nanotextured substrates for enhanced identification of
metastatic breast cancer cells.
AB - Metastasis is the major cause of low survival rates among cancer patients. Once
cancer cells metastasize, it is extremely difficult to contain the disease. We
report on a nanotextured platform for enhanced detection of metastatic cells. We
captured metastatic (MDA-MDB-231) and non-metastatic (MCF-7) breast cancer cells
on anti-EGFR aptamer modified plane and nanotextured substrates. Metastatic cells
were seen to change their morphology at higher rates when captured on
nanotextured substrates than on plane substrates. Analysis showed statistically
different morphological behaviors of metastatic cells that were very pronounced
on the nanotextured substrates. Several distance matrices were calculated to
quantify the dissimilarity of cell shape change. Nanotexturing increased the
dissimilarity of the metastatic cells and as a result the contrast between
metastatic and non-metastatic cells increased. Jaccard distance measurements
found that the shape change ratio of the non-metastatic and metastatic cells was
enhanced from 1:1.01 to 1:1.81, going from plane to nanotextured substrates. The
shape change ratio of the non-metastatic to metastatic cells improved from 1:1.48
to 1:2.19 for the Hausdorff distance and from 1:1.87 to 1:4.69 for the
Mahalanobis distance after introducing nanotexture. Distance matrix analysis
showed that nanotexture increased the shape change ratios of non-metastatic and
metastatic cells. Hence, the detectability of metastatic cells increased. These
calculated matrices provided clear and explicit measures to discriminate single
cells for their metastatic state on functional nanotextured substrates.
PMID- 28703711
TI - Interfacial properties of hydrides in alpha-Zr: a theoretical study.
AB - In order to better understand hydride formation in zirconium alloys, heterophase
interfaces between alpha-Zr and gamma-ZrH are investigated by means of ab initio
atomic-scale simulations of multilayers coupled with continuous elasticity. Our
approach allows us to separate out the elastic contribution, leading to basal and
prismatic [Formula: see text] interface energies around 200 [Formula: see text]
and 750 [Formula: see text] respectively, i.e. values noticeably higher than
previously found for coherent particles such as zeta-Zr2H. By considering
interfacial changes of H contents, the possibility of competing elasticity and
chemistry effects for interface stability is analyzed. The effects of the strong
anisotropy evident in [Formula: see text] interface energies on the important
practical issue of preferential habit planes are discussed, allowing us to
propose a plausible explanation for the experimental results.
PMID- 28703712
TI - Pump-probe STM light emission spectroscopy for detection of photo-induced
semiconductor-metal phase transition of VO2.
AB - We attempted to observe pump-probe scanning tunneling microscopy (STM)-light
emission (LE) from a VO2 thin film grown on a rutile TiO2(0 0 1) substrate, with
an Ag tip fixed over a semiconducting domain. Laser pulses from a Ti:sapphire
laser (wavelength 920 nm; pulse width less than 1.5 ps) irradiated the tip-sample
gap as pump and probe light sources. With a photon energy of 2.7 eV, suggesting
phase transition from semiconducting monoclinic (M) to metallic rutile (R) phases
in relation to the electronic band structure, faint LE was observed roughly 30 ps
after the irradiation of the pump pulse, followed by retention for roughly 20 ps.
The incident energy fluence of the pump pulse at the gap was five orders of
magnitude lower than the threshold value for reported photo-induced M-R phase
transition. The mechanism that makes it possible to reduce the threshold fluence
is discussed.
PMID- 28703713
TI - Consequences of the radiation accident at the Mayak production association in
1957 (the 'Kyshtym Accident').
AB - This paper presents an overview of the nuclear accident that occurred at the
Mayak Production Association (PA) in the Russian Federation on 29 September 1957,
often referred to as 'Kyshtym Accident', when 20 MCi (740 PBq) of radionuclides
were released by a chemical explosion in a radioactive waste storage tank. 2 MCi
(74 PBq) spread beyond the Mayak PA site to form the East Urals Radioactive Trace
(EURT). The paper describes the accident and gives brief characteristics of the
efficacy of the implemented protective measures that made it possible to
considerably reduce doses to the exposed population. The paper also provides
retrospective dosimetry estimates for the members of the EURT Cohort (EURTC)
which comprises approximately 21 400 people. During the first two years after the
accident a decrease in the group average leukocyte (mainly due to neutrophils and
lymphocytes) and thrombocyte count was observed in the population. At later dates
an increased excess relative risk of solid cancer incidence and mortality was
found in the EURTC.
PMID- 28703714
TI - Properties of the antiferromagnetic selenite MnSeO3 and its non-magnetic analogue
ZnSnO3 from first principles calculations.
AB - We report the properties of the antiferromagnetic selenite MnSeO3 and the non
magnetic analogue ZnSeO3, based on first principles calculations. These compounds
are rare examples of ABO3 perovskites with a tetravalent A-site and a divalent B
site. The electronic structure is discussed in the context of the bonding and
crystal structure. There is cross-gap hybridization between the O p states that
form the valence bands of these compounds and the unoccupied p states of Se,
reflecting the lone pair physics that leads to the strong off-centering of Se
from the perovskite A-site. The G-type antiferromagnetism of MnSeO3 is a local
moment in nature arising from high spin [Formula: see text] with short range
interactions. Additionally, there is an interesting spin-dependent hybridization
of Mn d and O p states analogous to that in colossal magnetoresistance
manganites.
PMID- 28703715
TI - Excitations in Quantum Liquids.
AB - Progress made in measuring and interpreting the elementary excitations of
superfluid and normal liquid ?4he in the past 25 years is reviewed. The goal is
to bring up to date the data, calculations and our understanding of the
excitations since the books and reviews of the early 1990s. Only bulk liquid ?4he
is considered. Reference to liquid ?3he, mixtures, reduced dimensions (films and
confined helium) is made where useful to enhance interpretation. The focus is on
the excitations as measured by inelastic neutron scattering methods. The review
covers the dynamic response of liquid ?4he from the collective excitations at low
energy and long wavelength (i.e. phonon-roton modes) to the single particle
excitations at high energy from which the atomic momentum distribution and Bose
Einstein condensate fraction are determined. A goal is to show the interplay of
these excitations with other spectacular properties such as superfluidity and the
test of fundamental calculations of quantum liquids that is possible. The role of
Bose-Einstein condensation in determining the nature of the ?pr~ mode and
particularly it's temperature dependence is emphasized. The similarity of normal
liquid ?4he with other quantum and classical liquids is discussed.
.
PMID- 28703716
TI - Effective spin Hamiltonian of a gated triple quantum dot in the presence of spin
orbit interaction.
AB - We derive and study the effective spin Hamiltonian of a gated triple quantum dot
that includes the effects of spin-orbit interaction and an external magnetic
field. In the analysis of the resulting spin interaction in linear and in general
triangular geometry of the dots, we show that the pairwise spin interaction does
depend on the position of the third dot. The spin-orbit induced anisotropy, in
addition to changing its strength, also changes its symmetry with the motion of
the third quantum dot outside the linear arrangement. Our results present a
simplified model that may be used in the design of quantum computers based on
three-spin qubits.
PMID- 28703717
TI - Therapeutic Drug Monitoring of Biopharmaceuticals May Benefit From
Pharmacokinetic and Pharmacokinetic-Pharmacodynamic Modeling.
AB - Biopharmaceuticals, especially monoclonal antibodies, have been increasingly used
to treat several chronic inflammatory diseases. Due to the complexity of their
pharmacokinetics and concentration-effect relationship, therapeutic drug
monitoring (TDM) has been used to optimize their dosing regimen. Up to date,
several decisional algorithms have been developed to provide tools for monoclonal
antibodies' therapeutic drug monitoring. However, these algorithms are unable to
determine the individual optimal dosing scheme. The aim of this article is to
deal with population pharmacokinetic (PK) and pharmacokinetic-pharmacodynamic (PK
PD) modeling. Allowing the quantification of the variability of the dose
concentration-response relationship, population pharmacokinetic-pharmacodynamic
modeling may be a valuable tool to determine the optimal dosing scheme. Based on
population modeling, Bayesian estimators may be developed to optimize dosing
schemes for each patient using limited sampling strategies. These estimators may
allow accurate dosing adjustment for each patient individually.
PMID- 28703718
TI - Current Practices for Therapeutic Drug Monitoring of Biopharmaceuticals in
Pediatrics.
AB - Biopharmaceuticals have recently emerged as effective treatments for refractory
pediatric autoimmune conditions. Several reports have shown a relationship
between drug concentration, antidrug antibodies, and clinical response in these
patients, strongly suggesting the potential interest, usefulness, and reliability
of therapeutic drug monitoring (TDM) in children. This article reviews the
current state of research in juvenile idiopathic arthritis, pediatric
inflammatory bowel disease, and pediatric psoriasis from a TDM point of view.
There is a remarkable lack of evidence-based data in pediatric patients, which is
reflected throughout the article. Most investigations of TDM are focused on
research of tumor necrosis factor alpha antagonists in inflammatory bowel
disease, albeit preliminary publications are emerging from pediatric
rheumatologists and dermatologists. To date, immunogenicity has been a primary
concern, particularly regarding infliximab and adalimumab therapy in children, as
it may lead to a loss of therapeutic response. Preliminary investigations show
that adjusting the dose according to blood drug concentrations improves disease
outcomes by overcoming antidrug antibodies, suggesting a crucial role for TDM.
Patients who receive other drugs, such as etanercept, abatacept, or tocilizumab,
could benefit from TDM because dosage can be optimized by adjusting it to the
minimum effective dose.
PMID- 28703719
TI - Pharmacokinetics of Antibiotics in Sub-Saharan African Patient Populations: A
Systematic Review.
AB - BACKGROUND: In sub-Saharan Africa (SSA), severe febrile illness accounts for a
large majority of medical admissions. SSA patients may also suffer from cachexia
and organ dysfunction resulting from tuberculosis, hepatitis B, and hypertension.
It is hard to tell how these conditions influence the pharmacokinetics (PK) of
antibiotics in this population. The aim of this systematic review was to
summarize antibiotic PK data of SSA adult patient populations to clarify whether
inappropriate drug concentrations that may also lead to antimicrobial resistance
are likely to occur. METHODS: An electronic search was conducted in Ovid MEDLINE,
Embase, and the African Index Medicus collecting studies from 1946 to May 2016.
Reviewers independently selected studies reporting outcome data on volume of
distribution (V), clearance, and half-life. Relevant information was abstracted
and quality assessed. RESULTS: Twelve studies were selected, addressing 6
antibiotic classes. There were 6 studies on fluoroquinolones and 1 on beta-lactam
antibiotics. Nine out of 12 originated from South Africa and 6 of those dealt
with intensive care unit (ICU) populations. The quality of most studies was low.
Studies on amikacin, teicoplanin, and ertapenem (n = 4) displayed a pattern of a
large V with low drug concentrations. Fluoroquinolone PK changes were less
prominent and more diverse whereas the probability of pharmacodynamic target
attainment was low for the treatment of tuberculosis in South Africa.
Interindividual variability of V was high for 10/12 studies. CONCLUSIONS:
Antibiotic PK data of SSA adult patient populations are scarce, but disease
induced inappropriate drug concentrations do occur. Data from non-ICU, severely
ill patients, and beta-lactam data are particularly lacking, whereas beta-lactam
antibiotics are commonly used, and typically vulnerable to disease-induced PK
changes. Studies investigating the PK and pharmacodynamics of beta-lactam
antibiotics in severely ill, adult SSA patient populations are needed to improve
local antibiotic dosing strategies.
PMID- 28703720
TI - Therapeutic Drug Monitoring for Perampanel in Japanese Epilepsy Patients:
Influence of Concomitant Antiepileptic Drugs.
AB - BACKGROUND: Perampanel is a new antiepileptic drug (AED) that acts as a
noncompetitive alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA)
receptor antagonist and is mainly metabolized by cytochrome P450 (CYP) 3A4. This
study evaluated the influence of concomitant AEDs on the serum concentration
profile of perampanel. METHODS: A total of 215 serum samples obtained from 76
patients aged 12 years or older were analyzed for routine therapeutic drug
monitoring, and the concentration-to-dose ratio (CD ratio) of perampanel was
compared among patients on various AED regimens. RESULTS: In patients not taking
concomitant enzyme-inducing AEDs, the mean CD ratio was 3963 ng.mL.mg.kg (range:
1793-13,299). By contrast, the mean CD ratio was lower in patients using enzyme
inducing AEDs [1760 (range: 892-3090), 2256 (range: 700-4703), and 1120 (range:
473-1853) ng.mL.mg.kg in patients taking phenytoin, phenobarbital, and
carbamazepine, respectively], and carbamazepine had a significantly greater
reduction in the CD ratio compared with phenytoin or phenobarbital (P < 0.001).
Twenty-one patients responded with >=50% reduction of seizure frequency from
baseline, and their mean serum perampanel concentration was 450 ng/mL (range: 85
1500). CONCLUSIONS: There is a large interindividual variation in CD ratio of
perampanel because its metabolism is highly susceptible to interactions with
enzyme-inducing AEDs. Therapeutic drug monitoring could be clinically useful for
determining the influence of AED CYP3A4 inducers on perampanel concentrations.
PMID- 28703721
TI - Minimizing rubidium-82 tracer activity for relative PET myocardial perfusion
imaging.
AB - OBJECTIVES: Recommended rubidium-82 activities for relative myocardial perfusion
imaging (MPI) using present-generation PET scanners may be unnecessarily high.
Our aim was to derive the minimum activity for a reliable relative PET MPI
assessment. MATERIALS AND METHODS: We analyzed 140 scans from 28 consecutive
patients who underwent rest-stress MPI-PET (Ingenuity TF). Scans of 852, 682,
511, and 341 MBq were simulated from list-mode data and compared with a reference
scan using 1023 MBq. Differences in the summed rest score, total perfusion
deficit, and image quality were obtained between the reference and each of the
simulated rest scans. Combined stress-rest scans obtained at a selected activity
of 682 MBq were diagnostically interpreted by experts and outcome was compared
with the reference scan interpretation. RESULTS: Differences in summed rest score
more than or equal to 3 were found using 682, 511, and 341 MBq in two (7%), four
(14%), and five (18%) patients, respectively. Differences in total perfusion
deficit more than 7% were only found at 341 MBq in one patient. Image quality
deteriorated significantly only for the 341 MBq scans (P<0.001). Interpretation
of stress-rest scans did not differ between 682 and 1023 MBq scans. CONCLUSION: A
significant reduction in administered Rb-82 activity is feasible in relative MPI.
An activity of 682 MBq resulted in reliable diagnostic outcomes and image
quality, and can therefore be considered for clinical adoption.
PMID- 28703722
TI - The Number of Interviews Needed to Yield New Syphilis and Human Immunodeficiency
Virus Cases Among Partners of People Diagnosed With Syphilis, North Carolina,
2015.
AB - : Compare syphilis investigation yield among patient groups using number needed
to interview. GOAL: To increase investigation efficiency. STUDY DESIGN:
Retrospective review of North Carolina 2015 syphilis investigations, using the
number of cases needed to interview (NNTI) and the total number of cases and
contacts needed to interview (TNTI) to compare yield of new syphilis and human
immunodeficiency virus diagnoses between patient groups. RESULTS: We reviewed
1646 early syphilis cases and 2181 contacts; these yielded 241 new syphilis cases
(NNTI, 6.9; TNTI, 16.4) and 38 new human immunodeficiency virus cases (NNTI, 43).
Interviews of women (prevalence difference [PD] = 6%, 95% confidence interval
[CI], 12-16), patients <30 years old (PD = 5%, 95% CI, 1-8), and patients with
titer >1:16 (PD = 5%, 95% CI, 1-9) yielded more new syphilis cases in our
adjusted model; no other patient factors increased investigation yield.
CONCLUSIONS: The NNTI and TNTI are useful measures of efficiency. Prioritizing
early syphilis investigation by gender, rapid plasmin reagin titer, and age
provides small increases in efficiency; no other factors increased efficiency.
PMID- 28703723
TI - Mycoplasma genitalium Macrolide and Fluoroquinolone Resistance: Prevalence and
Risk Factors Among a 2013-2014 Cohort of Patients in Barcelona, Spain.
AB - BACKGROUND: Macrolide and fluoroquinolone resistance is alarmingly emerging in M.
genitalium worldwide. This article provides the first estimates of the current
prevalence of macrolide and fluoroquinolone resistance-mediating mutations in
Barcelona, Spain, and identifies risk factors associated with the acquisition of
these resistances. METHODS: The study was conducted retrospectively with
specimens submitted between February 2013 and March 2014 to the microbiology
department of the Vall d'Hebron Hospital, Barcelona, where M. genitalium was
detected using nucleic acid amplification methods. DNA sequencing of 23S
ribosomal RNA gene and parC was performed in the Statens Serum Institut,
Copenhagen, to detect genotypic macrolide and fluoroquinolone resistance markers,
respectively. RESULTS: Macrolide resistance-mediating mutations were detected in
35% (95% confidence interval, 24%-47%) of the M. genitalium-positive episodes,
whereas 8% (95% confidence interval, 3%-17%) carried fluoroquinolone resistance
mutations. Of them, three cases harbored multidrug resistance to both classes of
antibiotics. Men who had sex with men (P = 0.002) and treatment with azithromycin
within the previous 12 months (P = 0.006) were strongly associated with macrolide
resistance. CONCLUSION: The widespread appearance of resistances, also in Spain,
makes imperative the implementation of combined diagnostic-resistance detection
assays for M. genitalium to facilitate the optimization of antibiotic treatment
in the management of nongonococcal urethritis and potentially reduce the
transmission of resistances.
PMID- 28703724
TI - Mycoplasma genitalium on the Loose: Time to Sound the Alarm.
PMID- 28703725
TI - Narrative Review: Sexually Transmitted Diseases and Homeless Youth-What Do We
Know About Sexually Transmitted Disease Prevalence and Risk?
AB - BACKGROUND: Homelessness affects an estimated 1.6 million US youth annually.
Compared with housed youth, homeless youth are more likely to engage in high-risk
behaviors, including inconsistent condom use, multiple sex partners, survival
sex, and alcohol/drug use, putting them at increased sexually transmitted disease
(STD) risk. However, there is no national estimate of STD prevalence among this
population. METHODS: We identified 10 peer-reviewed articles (9 unique studies)
reporting STD prevalence among homeless US youth (2000-2015). Descriptive and
qualitative analyses identified STD prevalence ranges and risk factors among
youth. RESULTS: Eight studies reported specific STD prevalence estimates, mainly
chlamydia, gonorrhea, and syphilis. Overall STD prevalence among homeless youth
ranged from 6% to 32%. STD rates for girls varied from 16.7% to 46%, and from 9%
to 13.1% in boys. Most studies were conducted in the Western United States, with
no studies from the Southeast or Northeast. Youths who experienced longer periods
of homelessness were more likely to engage in high-risk sexual behaviors. Girls
had lower rates of condom use and higher rates of STDs; boys were more likely to
engage in anal and anonymous sex. Additionally, peer social networks contributed
to protective effects on individual sexual risk behavior. CONCLUSIONS: Sexually
transmitted disease prevalence estimates among homeless youth fluctuated greatly
by study. Sexually transmitted disease risk behaviors are associated with unmet
survival needs, length of homelessness, and influence of social networks. To
promote sexual health and reduce STD rates, we need better estimates of STD
prevalence, more geographic diversity of studies, and interventions addressing
the behavioral associations identified in our review.
PMID- 28703726
TI - Motherhood and Risk for Human Immunodeficiency Virus/Sexually Transmitted
Infections Among Female Sex Workers in the Mexico-US Border Region.
AB - BACKGROUND: Globally, female sex workers (FSWs) have been identified as a high
risk group for human immunodeficiency virus (HIV) and sexually transmitted
infections (STIs). However, as women of reproductive age, FSWs also have
children. Few studies have investigated if financial responsibilities associated
with motherhood increase women's vulnerability to HIV and STIs among FSWs.
METHODS: From March 2013 to March 2014, 603 FSWs aged >=18 years were recruited
from Tijuana and Ciudad Juarez (Mexico) to participate in a study assessing
HIV/STI risk environments. RESULTS: Findings from logistic regression models
indicate that FSWs who reported motherhood were more likely to report (in the
past 30 days): a higher client volume (>30 clients) (adjusted odds ratio [AOR],
1.91; 95% confidence interval [CI], 1.27-2.87) and always using alcohol right
before or during sex with clients in the past 30 days (AOR, 1.77; 95% CI, 1.19
2.61). In contrast, they were more likely to report consistent condom use for
vaginal or anal sex with clients (AOR, 1.68; 95% CI, 1.10-2.55), less likely to
report using drugs right before or during sex with clients (AOR, 0.38; 95% CI,
0.26-0.56) and less likely to have tested positive for STIs at baseline (AOR,
0.63; 95% CI, 0.43-0.91). CONCLUSIONS: These results provide a glimpse of the
complex relationship between motherhood and women who are sex workers.
Understanding the convergence of motherhood and sex work and how this can
influence a woman's decision when engaging in sex work and affect her health is
essential to designing effective programs addressing reduce risk for HIV and STIs
among FSWs in this region and elsewhere.
PMID- 28703727
TI - Prevalence and Risk Factors for Rectal and Urethral Sexually Transmitted
Infections From Self-Collected Samples Among Young Men Who Have Sex With Men
Participating in the Keep It Up! 2.0 Randomized Controlled Trial.
AB - BACKGROUND: Despite recommendations that sexually active men who have sex with
men be regularly tested for sexually transmitted infections (STIs) and that
testing reflect anatomical sites of potential exposure, regular testing is not
widely performed, especially for rectal STIs. As such, little is known about the
prevalence of rectal and urethral STIs among young men who have sex with men
(YMSM). METHODS: The current study examined the prevalence and risk factors for
rectal and urethral chlamydia and gonorrhea in a sample of 1113 YMSM ages 18 to
29 years (mean, 24.07 years). Before participating in a randomized controlled
trial for an online human immunodeficiency virus prevention program (Keep It Up!
2.0), participants completed self-report measures and self-collected urine and
rectal samples. Participants mailed samples to a laboratory for nucleic acid
amplification testing. Viability of self-collected samples was examined as a
potential method to increase STI screening for MSM without access to STI testing
clinics. RESULTS: Results indicated that 15.1% of participants tested positive
for an STI, 13.0% for a rectal STI, 3.4% for a urethral STI, and 1.2% for both
rectal and urethral STIs. Rectal chlamydia was significantly more common (8.8%)
than rectal gonorrhea (5.0%). Rectal STIs were higher among black YMSM compared
with white YMSM. Additionally, rectal STIs were positively associated with
condomless receptive anal sex with casual partners. CONCLUSIONS: Findings call
attention to the need for health care providers to test YMSM for rectal STIs.
This study also demonstrates the viability of including self-collected samples
for STI testing in an eHealth program.
PMID- 28703728
TI - Urinary Meatal Swabbing Detects More Men Infected With Mycoplasma genitalium and
Four Other Sexually Transmitted Infections Than First Catch Urine.
AB - Urinary meatal swabs compared with urine showed higher infection rates for
Mycoplasma genitalium (15.3% vs 12.6%, P = 0.035), Chlamydia trachomatis (11.3%
vs 9.3%, P = 0.039), Neisseria gonorrhoeae (1.4% vs 1.1%, P = 1.00), Trichomonas
vaginalis (8.0% vs 1.7%, P < 0.001), and high-risk human papillomavirus (5.9% vs
3.4%, P = 0.078) respectively.
PMID- 28703729
TI - A Case of Decreased Susceptibility to Ceftriaxone in Neisseria gonorrhoeae in the
Absence of a Mosaic Penicillin-Binding Protein 2 (penA) Allele.
AB - We report a case of Neisseria gonorrhoeae with a non-mosaic penA allele that
exhibited decreased susceptibility to extended-spectrum cephalosporins, including
a ceftriaxone minimum inhibitory concentration of 0.5 MUg/mL. An analysis of
resistance determinants suggested that the observed phenotype might have resulted
from the combined effects of mutations in multiple genes.
PMID- 28703730
TI - An Illustration of Errors in Using the P Value to Indicate Clinical Significance
or Epidemiological Importance of a Study Finding.
AB - We conducted a simulation study to illustrate that P values can suggest but not
confirm statistical significance; and they may not indicate epidemiological
significance (importance). We recommend that researchers consider reporting
effect sizes as P values in conjunction with confidence intervals or point
estimates with standard errors to indicate precision (uncertainty).
PMID- 28703731
TI - Effectiveness of Prenatal Screening and Treatment to Prevent Congenital Syphilis,
Louisiana and Florida, 2013-2014.
AB - BACKGROUND: From 2012 to 2014, rates of congenital syphilis increased in
Louisiana and Florida. We evaluated the effectiveness of early (first or second)
and third trimester syphilis screening for the prevention of congenital syphilis
in these high-morbidity states. METHODS: Reported syphilis cases among pregnant
women in Louisiana and Florida during January 1, 2013, to December 31, 2014, were
reviewed for documented screening for syphilis in the first 2 trimesters and
third trimester. Pregnant women with syphilis were linked to congenital syphilis
records and stratified by whether the pregnancy led to a reported congenital
syphilis case. RESULTS: Seven hundred ten pregnant women with syphilis in
Louisiana and Florida were linked to 155 congenital syphilis cases. Three hundred
seventy (52%) pregnant women with syphilis were staged as early syphilis (n =
270) or high-titer late or unknown duration-latent syphilis (n = 100), and 109
(70% of the total) were linked to congenital syphilis cases. Screening in the
first 2 trimesters identified 513 pregnant women who tested positive for
syphilis, and 470 (92%) potential congenital syphilis were averted. One hundred
nine pregnant women tested positive for syphilis in the third trimester, and 85
(78%) had babies without congenital syphilis. During their pregnancy, 85 (12%)
women tested negative at least once, and 55 (65%) had babies with congenital
syphilis. Thirty-nine women had no reported syphilis screening 30 days or longer
before delivery. CONCLUSIONS: Screening for syphilis both early and in the third
trimester prevented many pregnant women with syphilis from having a baby with
congenital syphilis. Preventing all congenital syphilis would likely require
preventing all syphilis among women.
PMID- 28703732
TI - Congenital Syphilis: Time for a National Prevention Program.
PMID- 28703733
TI - US Public Sexually Transmitted Disease Clinical Services in an Era of Declining
Public Health Funding: 2013-14.
AB - BACKGROUND: We examined the infrastructure for US public sexually transmitted
disease (STD) clinical services. METHODS: In 2013 to 2014, we surveyed 331 of
1225 local health departments (LHDs) who either reported providing STD
testing/treatment in the 2010 National Profile of Local Health Departments survey
or were the 50 local areas with the highest STD cases or rates. The sample was
stratified by jurisdiction population size. We examined the primary referral
clinics for STDs, the services offered and the impact of budget cuts (limited to
government funding only). Data were analyzed using SAS, and analyses were
weighted for nonresponse. RESULTS: Twenty-two percent of LHDs cited a specialty
STD clinic as their primary referral for STD services; this increased to 53.5% of
LHDs when combination STD-family planning clinics were included. The majority of
LHDs (62.8%) referred to clinics providing same-day services. Sexually
transmitted disease clinics more frequently offered extragenital testing for
chlamydia and/or gonorrhea (74.7%) and gonorrhea culture (68.5%) than other
clinics (52.9%, 46.2%, respectively; P < 0.05). The majority of LHDs (61.5%)
reported recent budget cuts. Of those with decreased budgets, the most common
impacts were fewer clinic hours (42.8%; 95% confidence interval [CI], 24.4-61.2),
reduced routine screening (40.2%; 95% CI, 21.7-58.8) and reductions in partner
services (42.1%; 95% CI, 23.6-60.7). One quarter of those with reduced STD
budgets increased fees or copays for clients. CONCLUSIONS: Findings demonstrate
gaps and reductions in US public STD services including clinical services that
play an important role in reducing disease transmission. Furthermore, STD clinics
tended to offer more specialized STD services than other public clinics.
PMID- 28703734
TI - A New Resource for STD Clinical Providers: The Sexually Transmitted Diseases
Clinical Consultation Network.
AB - An online consultation tool, the Sexually Transmitted Diseases Clinical
Consultation Network is a new resource for sexually transmitted disease
clinicians and clinic managers. An initial evaluation shows that most requests
(29%) were from medical doctors, followed by nurse practitioners (22%). Syphilis
queries comprised 39% of consults followed by gonorrhea (12%) and chlamydia
(11%).
PMID- 28703735
TI - Coffee Consumption and Heart Rate Variability: The Brazilian Longitudinal Study
of Adult Health (ELSA-Brasil) Cohort Study.
AB - : Studies have shown that acute coffee ingestion can affect cardiovascular
autonomic activity, although the chronic effects on heart rate variability (HRV)
remain controversial. METHOD: A cross-sectional study with baseline data (2008
2010) from ELSA-Brasil cohort of 15,105 (aged 35-74), based in six Brazilian
states. Coffee consumption in the previous 12 months was measured using the semi
quantitative food frequency questionnaire, and HRV was obtained through
electrocardiographic tracings during 10 min at rest. Independent association
between the frequency of coffee consumption "never or almost never", "<=1
cup/day", "2-3 cups/day", ">=3 cups/day", and HRV was estimated using generalized
linear regression, adjusting for socio-demographic characteristics, health
related behavior, markers of abnormal metabolism, and the presence of coronary
artery disease. Further, we applied Bonferroni correction in the full models.
RESULTS: The mean age was 52 years (standard deviation (SD) = 9.1), and 52% was
female; 9.5% never/almost never consumed coffee. In univariate analysis, coffee
consumers had reduced values of HRV indexes, but after full adjustments and
correction for multiple comparisons, these associations disappeared. A trend of
reduction in HRV vagal indexes was observed in those that consumed >=3 cups of
coffee/day. CONCLUSION: Most of the effects attributed to the chronic use of
coffee on the HRV indexes is related to the higher prevalence of unhealthy habits
in coffee users, such as smoking and alcohol use. Adjustment for confounding
factors weaken this association, making it non-significant. The effect of higher
daily doses of coffee on the autonomic system should be evaluated in further
studies.
PMID- 28703736
TI - Nephroprotective Effects of Saponins from Leaves of Panax quinquefolius against
Cisplatin-Induced Acute Kidney Injury.
AB - Although cisplatin is an anticancer drug that has activity against malignant
tumor, it often causes nephrotoxicity. Previous reports have confirmed that the
saponins from the leaves of P. quinquefolium (PQS) exerted many pharmacological
activities. However, the renoprotective effects of PQS were still unknown. The
purpose of the present research was to discuss renoprotective effect of PQS in a
mouse model of cisplatin-induced acute kidney injury (AKI). The levels of blood
urea nitrogen (BUN) and serum creatinine (CRE) were evidently increased in
cisplatin-intoxicated mice, which were reversed by PQS. Renal oxidative stress,
evidenced by increased malondialdehyde (MDA) level and decline of glutathione
(GSH) and superoxide dismutase (SOD) activities, was significantly alleviated by
PQS pretreatment. The suppression of inflammatory response by PQS was realized
through the decrease the mRNA expression levels of tumor necrosis factor-alpha
(TNF-alpha) and interleukin-1beta (IL-1beta) in kidney tissues, which were
measured by quantitative real-time polymerase chain reaction (qRT-PCR).
Simultaneously, the overexpression of cytochrome P450 E1 (CYP2E1) and heme
oxygenase-1 (HO-1) were attenuated by PQS. Furthermore, the effects of Western
blotting demonstrated that PQS administration significantly suppressed the
protein expression levels of nicotinamide adenine dinucleotide phosphate oxidase
type 4 (Nox4), cleaved Caspase-3, cleaved Caspase-9, Bax, nuclear factor-kappaB
(NF-kappaB), cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase
(iNOS), suggesting the inhibition of apoptosis and inflammation response.
Overall, PQS may possess protective effects in cisplatin-induced AKI through
suppression of oxidative stress, inflammation and apoptosis.
PMID- 28703737
TI - Special Issue Introduction: Role of Epigenetic Gene Regulation in Brain Function.
AB - In 1957, Conrad H. Waddington published a paper in which he demonstrated the
inheritance of an acquired characteristic in a population in response to an
environmental stimulus [1].[...].
PMID- 28703738
TI - Abnormally Increased Secretion in Olfactory Neuronal Precursors from a Case of
Schizophrenia Is Modulated by Melatonin: A Pilot Study.
AB - The alterations that underlie the pathophysiology of schizophrenia (SCZ) include
the dysregulation of structural and functional properties of neurons. Among
these, the secretion of neurotransmitters and hormones, which plays a key role
for neuronal communication and development, is altered. Neuronal precursors from
the human olfactory epithelium have been recently characterized as a reliable
model for studying the etiopathogenesis of neuropsychiatric diseases. Our
previous work has shown that melatonin enhances the development of morphological
and functional features of cloned olfactory neuronal precursors (ONPs) from a
healthy subject. In this work we found that primary cultures of ONPs obtained
from a schizophrenic patient display an increased potassium-evoked secretion,
when compared with ONPs from an age- and gender-matched healthy control subject
(HCS). Secretion was evaluated by FM1-43 fluorescence cumulative changes in
response to depolarization. Interestingly, a 12 h-melatonin treatment modulated
the abnormally increased secretion in SCZ ONPs and brought it to levels similar
to those found in the HCS ONPs. Our results suggest that the actin cytoskeleton
might be a target for melatonin effects, since it induces the thickening of actin
microfilament bundles. Further research will address the mechanisms by which
melatonin modulates neurochemical secretion from ONPs.
PMID- 28703739
TI - The SBP-Box Gene VpSBP11 from Chinese Wild Vitis Is Involved in Floral Transition
and Affects Leaf Development.
AB - Flowering occurs in angiosperms during a major developmental transition from
vegetative growth to the reproductive phase. Squamosa promoter binding protein
(SBP)-box genes have been found to play critical roles in regulating flower and
fruit development, but their roles in grapevine have remained unclear. To better
understand the functions of the grape SBP-box genes in both vegetative and
reproductive growth phases, a full-length complementary DNA (cDNA) sequence of
the putative SBP-box transcription factor gene, VpSBP11, was obtained from
Chinese wild grapevine Vitis pseudoreticulata Wen Tsai Wang (W. T. Wang) clone
'Baihe-35-1'. VpSBP11 encoded a putative polypeptide of 170 amino acids with a
highly conserved SBP-domain with two zinc-binding sites of the Cx2C-x3-H-x11-C-x6
H (C2HCH) type and a nuclear localization signal. We confirmed that the VpSBP11
protein was targeted to the nucleus and possessed transcriptional activation
activity by subcellular localization and trans-activation assay. Over-expression
of VpSBP11 in Arabidopsis thaliana was shown to activate the FUL gene, and
subsequently the AP1 and LFY genes, all of which were floral meristem identity
genes, and to cause earlier flowering than in wild type (WT) plants. The pattern
of vegetative growth was also different between the transgenic and WT plants. For
example, in the VpSBP11 over-expressing transgenic plants, the number of rosette
leaves was less than that of WT; the petiole was significantly elongated; and the
rosette and cauline leaves curled upwards or downwards. These results were
consistent with VpSBP11 acting as a transcription factor during the transition
from the vegetative stage to the reproductive stage.
PMID- 28703740
TI - Investigation of Antibacterial and Fouling Resistance of Silver and Multi-Walled
Carbon Nanotubes Doped Poly(Vinylidene Fluoride-co-Hexafluoropropylene) Composite
Membrane.
AB - Composite membranes were successfully prepared using a phase-inversion method.
The X-ray powder diffraction (XRD) and energy dispersive X-ray (EDX) profiles has
confirmed formation of 4.8 wt % Ag/poly(vinylidene fluoride-co-hexafluoropropene)
(PVDF-HFP), 3 wt % Ag-MWCNTs/PVDF-HFP (EDX surface composition of Ag
nanoparticles) and 1.5 wt % MWCNTs/PVDF-HFP composite membranes. The MWCNTs
crystallites are mainly encapsulated by a layer of PVDF-HFP, as evidenced by
disappearance of graphitic peak. The scanning electron microscopy (SEM) images
have depicted the formation of microporous structure, with few MWCNTs on the
surface and strongly interacting with PVDF-HFP as demonstrated by
thermogravimetric analysis (TGA), XRD and Fourier transform infrared (FTIR) data.
The data indicated an increase in porosity, swellability and water content of the
PVDF-HFP membrane with the addition of MWCNTs and/or Ag nanoparticles, showing an
improved hydrophilicity. The 1.5 wt % MWCNTs/PVDF-HFP composite membrane showed
good desalination and fouling resistance rates, which correlates with a low water
contact angle. The combined effects of Ag nanoparticles and MWCNTs do not promote
fouling resistance of PVDF-HFP membranes, as shown during NaCl microfiltration
(this is linked with high water contact angle as compared to that of MWCNTs/PVDF
HFP composite). Both 1.5 wt % MWCNTs/PVDF-HFP and 3 wt % Ag-MWCNTs/PVDF-HFP
composite membranes prevented the bacteria passing through the membrane (100%
bacterial load reduction). The surface of 3 wt % Ag-MWCNTs/PVDF-HFP showed good
bactericidal and non-leaching properties of the dopant materials (MWCNTs and Ag),
as evidenced by bacterial growth on the edges of the membranes.
PMID- 28703741
TI - Novel Substrates as Sources of Ancient DNA: Prospects and Hurdles.
AB - Following the discovery in the late 1980s that hard tissues such as bones and
teeth preserve genetic information, the field of ancient DNA analysis has
typically concentrated upon these substrates. The onset of high-throughput
sequencing, combined with optimized DNA recovery methods, has enabled the
analysis of a myriad of ancient species and specimens worldwide, dating back to
the Middle Pleistocene. Despite the growing sophistication of analytical
techniques, the genetic analysis of substrates other than bone and dentine remain
comparatively "novel". Here, we review analyses of other biological substrates
which offer great potential for elucidating phylogenetic relationships,
paleoenvironments, and microbial ecosystems including (1) archaeological
artifacts and ecofacts; (2) calcified and/or mineralized biological deposits; and
(3) biological and cultural archives. We conclude that there is a pressing need
for more refined models of DNA preservation and bespoke tools for DNA extraction
and analysis to authenticate and maximize the utility of the data obtained. With
such tools in place the potential for neglected or underexploited substrates to
provide a unique insight into phylogenetics, microbial evolution and evolutionary
processes will be realized.
PMID- 28703742
TI - Assays to Monitor Autophagy in Saccharomyces cerevisiae.
AB - Autophagy is an intracellular process responsible for the degradation and
recycling of cytoplasmic components. It selectively removes harmful cellular
material and enables the cell to survive starvation by mobilizing nutrients via
the bulk degradation of cytoplasmic components. While research over the last
decades has led to the discovery of the key factors involved in autophagy, the
pathway is not yet completely understood. The first studies of autophagy on a
molecular level were conducted in the yeast Saccharomyces cerevisiae. Building up
on these studies, many homologs have been found in higher eukaryotes. Yeast
remains a highly relevant model organism for studying autophagy, with a wide
range of established methods to elucidate the molecular details of the autophagy
pathway. In this review, we provide an overview of methods to study both
selective and bulk autophagy, including intermediate steps in the yeast
Saccharomyces cerevisiae. We compare different assays, discuss their advantages
and limitations and list potential applications.
PMID- 28703743
TI - Tracing the Repertoire of Promiscuous Enzymes along the Metabolic Pathways in
Archaeal Organisms.
AB - The metabolic pathways that carry out the biochemical transformations sustaining
life depend on the efficiency of their associated enzymes. In recent years, it
has become clear that promiscuous enzymes have played an important role in the
function and evolution of metabolism. In this work we analyze the repertoire of
promiscuous enzymes in 89 non-redundant genomes of the Archaea cellular domain.
Promiscuous enzymes are defined as those proteins with two or more different
Enzyme Commission (E.C.) numbers, according the Kyoto Encyclopedia of Genes and
Genomes (KEGG) database. From this analysis, it was found that the fraction of
promiscuous enzymes is lower in Archaea than in Bacteria. A greater diversity of
superfamily domains is associated with promiscuous enzymes compared to
specialized enzymes, both in Archaea and Bacteria, and there is an enrichment of
substrate promiscuity rather than catalytic promiscuity in the archaeal enzymes.
Finally, the presence of promiscuous enzymes in the metabolic pathways was found
to be heterogeneously distributed at the domain level and in the phyla that make
up the Archaea. These analyses increase our understanding of promiscuous enzymes
and provide additional clues to the evolution of metabolism in Archaea.
PMID- 28703744
TI - Novel Flexible Wearable Sensor Materials and Signal Processing for Vital Sign and
Human Activity Monitoring.
AB - Advances in flexible electronic materials and smart textile, along with broad
availability of smart phones, cloud and wireless systems have empowered the
wearable technologies for significant impact on future of digital and
personalized healthcare as well as consumer electronics. However, challenges
related to lack of accuracy, reliability, high power consumption, rigid or bulky
form factor and difficulty in interpretation of data have limited their wide
scale application in these potential areas. As an important solution to these
challenges, we present latest advances in novel flexible electronic materials and
sensors that enable comfortable and conformable body interaction and potential
for invisible integration within daily apparel. Advances in novel flexible
materials and sensors are described for wearable monitoring of human vital signs
including, body temperature, respiratory rate and heart rate, muscle movements
and activity. We then present advances in signal processing focusing on motion
and noise artifact removal, data mining and aspects of sensor fusion relevant to
future clinical applications of wearable technology.
PMID- 28703745
TI - The Construction and Characterization of Mitochondrial Ferritin Overexpressing
Mice.
AB - Mitochondrial ferritin (FtMt) is a H-ferritin-like protein which localizes to
mitochondria. Previous studies have shown that this protein can protect
mitochondria from iron-induced oxidative damage, while FtMt overexpression in
cultured cells decreases cytosolic iron availability and protects against
oxidative damage. To investigate the in vivo role of FtMt, we established FtMt
overexpressing mice by pro-nucleus microinjection and examined the
characteristics of the animals. We first confirmed that the protein levels of
FtMt in the transgenic mice were increased compared to wild-type mice.
Interestingly, we found no significant differences in the body weights or organ
to body weight ratios between wild type and transgenic mice. To determine the
effects of FtMt overexpression on baseline murine iron metabolism and
hematological indices, we measured serum, heart, liver, spleen, kidney, testis,
and brain iron concentrations, liver hepcidin expression and red blood cell
parameters. There were no significant differences between wild type and
transgenic mice. In conclusion, our results suggest that FtMt overexpressing mice
have no significant defects and the overexpression of FtMt does not affect the
regulation of iron metabolism significantly in transgenic mice.
PMID- 28703746
TI - Cudraflavone C Induces Apoptosis of A375.S2 Melanoma Cells through Mitochondrial
ROS Production and MAPK Activation.
AB - Melanoma is the most malignant form of skin cancer and is associated with a very
poor prognosis. The aim of this study was to evaluate the apoptotic effects of
cudraflavone C on A375.S2 melanoma cells and to determine the underlying
mechanisms involved in apoptosis. Cell viability was determined using the MTT and
real-time cytotoxicity assays. Flow cytometric evaluation of apoptosis was
performed after staining the cells with Annexin V-FITC and propidium iodide. The
mitochondrial membrane potential was evaluated using the JC-1 assay. Cellular ROS
production was measured using the CellROX assay, while mitochondrial ROS
production was evaluated using the MitoSOX assay. It was observed that
cudraflavone C inhibited growth in A375.S2 melanoma cells, and promoted apoptosis
via the mitochondrial pathway mediated by increased mitochondrial ROS production.
In addition, cudraflavone C induced phosphorylation of MAPKs (p38, ERK, and JNK)
and up-regulated the expression of apoptotic proteins (Puma, Bax, Bad, Bid, Apaf
1, cytochrome C, caspase-9, and caspase-3/7) in A375.S2 cells. Pretreatment of
A375.S2 cells with MitoTEMPOL (a mitochondria-targeted antioxidant) attenuated
the phosphorylation of MAPKs, expression of apoptotic proteins, and the overall
progression of apoptosis. In summary, cudraflavone C induced apoptosis in A375.S2
melanoma cells by increasing mitochondrial ROS production; thus, activating p38,
ERK, and JNK; and increasing the expression of apoptotic proteins. Therefore,
cudraflavone C may be regarded as a potential form of treatment for malignant
melanoma.
PMID- 28703747
TI - The Prostate Cancer Cells Resistant to Docetaxel as in vitro Model for
Discovering MicroRNAs Predictive of the Onset of Docetaxel Resistance.
AB - On the grounds that miRNAs present in the blood of prostate cancer (PCa) patients
are released in the growth medium by PCa cells, it is conceivable that PCa cells
resistant to docetaxel (DCT) (DCTR) will release miRNAs that may be found in PCa
patients under DCT therapy if resistant PCa cells appear. We isolated DCTR clones
respectively from 22Rv1 and DU-145 PCa cell lines and performed through next
generation sequencing (NGS) the miRNAs profiles of the released miRNAs. The
analysis of the NGS data identified 105 and 1 miRNAs which were differentially
released in the growth medium of the 22Rv1/DCTR and DU-145/DCTR clones,
respectively. Using additional filters, we selected 12 and 1 miRNA more released
by all 22Rv1/DCTR and DU-145/DCTR clones, respectively. Moreover, we showed that
6 of them were more represented in the growth medium of the DCTR cells than the
ones of DCT-treated cells. We speculated that they have the pre-requisite to be
tested as predictive biomarkers of the DCT resistance in PCa patients under DCT
therapy. We propose the utilization of clones resistant to a given drug as in
vitro model to identify the differentially released miRNAs, which in perspective
could be tested as predictive biomarkers of drug resistance in tumor patients
under therapy.
PMID- 28703748
TI - Content of the Saponin Protodioscin in Brachiaria spp. from the Eastern Plains of
Colombia.
AB - Protodioscin is used as a marker of saponin content that could cause
hepatotoxicity in ruminants. In Brachiaria spp. from two regions of the Colombian
Eastern Plains (east mountain range of the Andean-"piedemonte" and Ariari River
Valley) were determined this metabolite at 14 and 28 days post-cutting under
different climatic conditions. No protodioscin was detected in B. dictyoneura or
B. humidicola. In B. brizantha, B. decumbens and B. ruziziensis x B. decumbens x
B. brizantha (hybrid), protodioscin content corresponded to an interaction
between species, post-cutting time and season. Concentrations >=1% (minimum toxic
level) were recorded in B. decumbens and the hybrid, and to a lesser extent in B.
brizantha. The concentration of protodioscin was higher at 28 days, when the
pastures are suitable for consumption. B. brizantha accumulated the lowest
saponin concentration, whereas the hybrid had the highest levels, particularly in
the "piedemonte" and during drought (3.37%). Dry season favored the protodioscin
concentration in B. decumbens (in river valley) and in the hybrid (in
"piedemonte"). In the latter, there was a positive correlation with temperature
and a negative with humidity, which are typical characteristics of dry periods.
This is the first report of protodioscin content in the hybrid.
PMID- 28703750
TI - Effect of Distributed Mass on the Node, Frequency, and Sensitivity of Resonant
Mode Based Cantilevers.
AB - We derived an analytical expression for a resonant-mode based bi-layered
cantilever with distributed mass load. The behavior of mode of vibration, nodal
position, frequency shift, as well as sensitivity under different mass load
distributions was theoretically studied. The theoretical results suggested that
asymmetric mass load distribution leads to the shift of nodes as well as the
sensitive regions of a resonant-mode based cantilever. n - 1 local maximal
sensitivities and n - 1 local minimal sensitivities are observed when the
cantilever vibrates in the nth-order resonance. The maximal sensitivity is found
at the first local maximal sensitivity and the behavior of mass load length as a
function of the maximal sensitivity follows the rule of an exponent decaying
function. The sensitivity increases as the load mass increases for the same mass
load distribution, but the corresponding slopes are different.
PMID- 28703749
TI - The Application of Whole Cell-Based Biosensors for Use in Environmental Analysis
and in Medical Diagnostics.
AB - Various whole cell-based biosensors have been reported in the literature for the
last 20 years and these reports have shown great potential for their use in the
areas of pollution detection in environmental and in biomedical diagnostics.
Unlike other reviews of this growing field, this mini-review argues that: (1) the
selection of reporter genes and their regulatory proteins are directly linked to
the performance of celllular biosensors; (2) broad enhancements in
microelectronics and information technologies have also led to improvements in
the performance of these sensors; (3) their future potential is most apparent in
their use in the areas of medical diagnostics and in environmental monitoring;
and (4) currently the most promising work is focused on the better integration of
cellular sensors with nano and micro scaled integrated chips. With better
integration it may become practical to see these cells used as (5) real-time
portable devices for diagnostics at the bedside and for remote environmental
toxin detection and this in situ application will make the technology commonplace
and thus as unremarkable as other ubiquitous technologies.
PMID- 28703751
TI - Dental Providers' Perspectives on Diagnosis-Driven Dentistry: Strategies to
Enhance Adoption of Dental Diagnostic Terminology.
AB - The routine use of standardized diagnostic terminologies (DxTMs) in dentistry has
long been the subject of academic debate. This paper discusses the strategies
suggested by a group of dental stakeholders to enhance the uptake of DxTMs.
Through unstructured interviewing at the 'Toward a Diagnosis-Driven Profession'
National Conference held on 19 March 2016 in Los Angeles, CA, USA participants
were asked how enthusiastic they were about implementing and consistently using
DxTMs at their work. They also brainstormed on strategies to improve the
widespread use of DxTMs. Their responses are summarized by recursive abstraction
and presented in themes. Conference participants were very enthusiastic about
using a DxTM in their place of work. Participants enumerated several strategies
to make DxTMs more appealing including: the use of mandates, a value proposition
for providers, communication and education, and integration with EHRs and
existing systems. All groups across the dental healthcare delivery spectrum will
need to work together for the success of the widespread and consistent use of
DxTMs. Understanding the provider perspective is however the most critical step
in achieving this goal, as they are the group who will ultimately be saddled with
the critical task of ensuring DxTM use at the point of care.
PMID- 28703752
TI - Effects of Promotional Materials on Attitudes and Fear towards Colorectal Cancer
Screening among Chinese Older Adults: An Experimental Study.
AB - Colorectal cancer (CRC) screening is a cost-effective prevention and control
strategy. However, the promotion of CRC screening for older adults may be
difficult because reading CRC prevention information may evoke embarrassment,
fear, and anxiety towards the screening procedure and cancer diagnosis. This
study aims to (1) examine the effects of three promotional materials for CRC
screening on the attitudes toward CRC screening tests (screening interest,
screening effectiveness, and trust in the screening results) and cancer fear, and
(2) to explore the interaction effect of cancer fear with screening effectiveness
and trust in the screening results on screening interest of the three screening
tests (fecal occult blood test (FOBT), flexible sigmoidoscopy, and colonoscopy)
among Chinese older adults. A total of 114 community-dwelling older adults were
asked to look at the corresponding promotional materials (pamphlet, cartoon, and
video) of one of the three study groups. The pamphlet and video represent
convention strategies and the cartoon represents an innovative strategy. No
significant difference was observed in the screening interest and cancer fear
across groups. FOBT was the most preferred screening modality. The video group
has a large proportion agreed screening effectiveness of flexible sigmoidoscopy
than pamphlet and cartoon groups and trusted in the screening results for FOBT
and flexible sigmoidoscopy than the pamphlet group. Logistic regression results
showed that the effect of trust in the screening results on screening interest
for colonoscopy was greater among participants with higher cancer fear than those
with lower cancer fear level. In conclusion, the three promotional groups had
produced similar results in their attitudes toward CRC screening and cancer fear.
The use of cartoons may be a comparable approach with conventional methods in the
promotion of CRC screening. Additional components that can arouse fear and boost
response efficacy simultaneously might also be useful for the effective promotion
of colonoscopy among Chinese older adults.
PMID- 28703753
TI - Development of Antimicrobial Packaging Film Made from Poly(Lactic Acid)
Incorporating Titanium Dioxide and Silver Nanoparticles.
AB - Polylactide (PLA)/nano-TiO2 and PLA/nano-TiO2/nano-Ag blends films were prepared
by a solvent volatilization method. Compared to pure PLA film, the nano-blend
films have low water vapor permeability (WVP) and a poor transparency. With the
increase of the NPs in the PLA, the tensile strength (TS) and elastic modulus
(EM) decreased, while the elongation at break (epsilon) increased. SEM analysis
indicated a rougher cross-section of the nano-blend films. According to the FTIR
analysis, no new chemical bonds were formed in the nano-blend films. By using DSC
to examine the crystallization and melting behavior, the result shows that the
NPs have no effect on the glass transition (Tg) and melting temperature (Tm), but
they caused an increase on the cold crystallization (Tc) and crystallinity (Xc).
TGA results show that the addition of nanoparticles significantly improved the
thermal stability. The PLA nano-blend films show a good antimicrobial activity
against. E. coli and Listeria monocytogenes. Most important, we carried out
migration tests, and verified that the release of NPs from the nano-blend films
was within the standard limits.
PMID- 28703754
TI - Synchronization of Human Autonomic Nervous System Rhythms with Geomagnetic
Activity in Human Subjects.
AB - A coupling between geomagnetic activity and the human nervous system's function
was identified by virtue of continuous monitoring of heart rate variability (HRV)
and the time-varying geomagnetic field over a 31-day period in a group of 10
individuals who went about their normal day-to-day lives. A time series
correlation analysis identified a response of the group's autonomic nervous
systems to various dynamic changes in the solar, cosmic ray, and ambient magnetic
field. Correlation coefficients and p values were calculated between the HRV
variables and environmental measures during three distinct time periods of
environmental activity. There were significant correlations between the group's
HRV and solar wind speed, Kp, Ap, solar radio flux, cosmic ray counts, Schumann
resonance power, and the total variations in the magnetic field. In addition, the
time series data were time synchronized and normalized, after which all circadian
rhythms were removed. It was found that the participants' HRV rhythms
synchronized across the 31-day period at a period of approximately 2.5 days, even
though all participants were in separate locations. Overall, this suggests that
daily autonomic nervous system activity not only responds to changes in solar and
geomagnetic activity, but is synchronized with the time-varying magnetic fields
associated with geomagnetic field-line resonances and Schumann resonances.
PMID- 28703755
TI - beta-Ocimene, a Key Floral and Foliar Volatile Involved in Multiple Interactions
between Plants and Other Organisms.
AB - beta-Ocimene is a very common plant volatile released in important amounts from
the leaves and flowers of many plant species. This acyclic monoterpene can play
several biological functions in plants, by potentially affecting floral visitors
and also by mediating defensive responses to herbivory. The ubiquity and high
relative abundance of beta-ocimene in the floral scents of species from most
plant families and from different pollination syndromes (ranging from generalism
to specialism) strongly suggest that this terpenoid may play an important role in
the attraction of pollinators to flowers. We compiled abundant evidence from
published studies that supports beta-ocimene as a generalist attractant of a wide
spectrum of pollinators. We found no studies testing behavioural responses of
pollinators to beta-ocimene, that could directly demonstrate or deny the function
of beta-ocimene in pollinator attraction; but several case studies support that
the emissions of beta-ocimene in flowers of different species follow marked
temporal and spatial patterns of emission, which are typical from floral volatile
organic compound (VOC) emissions that are involved in pollinator attraction.
Furthermore, important beta-ocimene emissions are induced from vegetative plant
tissues after herbivory in many species, which have relevant functions in the
establishment of tritrophic interactions. We thus conclude that beta-ocimene is a
key plant volatile with multiple relevant functions in plants, depending on the
organ and the time of emission. Experimental behavioural studies on pure beta
ocimene conducted with pollinating insects will be necessary to prove the
assumptions made here.
PMID- 28703756
TI - Green Streets: Urban Green and Birth Outcomes.
AB - Recent scholarship points to a protective association between green space and
birth outcomes as well a positive relationship between blue space and wellbeing.
We add to this body of literature by exploring the relationship between expectant
mothers' exposure to green and blue spaces and adverse birth outcomes in New York
City. The Normalized Difference Vegetation Index (NDVI), the NYC Street Tree
Census, and access to major green spaces served as measures of greenness, while
proximity to waterfront areas represented access to blue space. Associations
between these factors and adverse birth outcomes, including preterm birth, term
birthweight, term low birthweight, and small for gestational age, were evaluated
via mixed-effects linear and logistic regression models. The analyses were
conducted separately for women living in deprived neighborhoods to test for
differential effects on mothers in these areas. The results indicate that women
in deprived neighborhoods suffer from higher rates adverse birth outcomes and
lower levels of residential greenness. In adjusted models, a significant inverse
association between nearby street trees and the odds of preterm birth was found
for all women. However, we did not identify a consistent significant relationship
between adverse birth outcomes and NDVI, access to major green spaces, or
waterfront access when individual covariates were taken into account.
PMID- 28703757
TI - Oil Palm Waste-Based Precursors as a Renewable and Economical Carbon Sources for
the Preparation of Reduced Graphene Oxide from Graphene Oxide.
AB - Herein, a new approach was proposed to produce reduced graphene oxide (rGO) from
graphene oxide (GO) using various oil palm wastes: oil palm leaves (OPL), palm
kernel shells (PKS) and empty fruit bunches (EFB). The effect of heating
temperature on the formation of graphitic carbon and the yield was examined prior
to the GO and rGO synthesis. Carbonization of the starting materials was
conducted in a furnace under nitrogen gas for 3 h at temperatures ranging from
400 to 900 degrees C and a constant heating rate of 10 degrees C/min. The GO
was further synthesized from the as-carbonized materials using the 'improved
synthesis of graphene oxide' method. Subsequently, the GO was reduced by low
temperature annealing reduction at 300 degrees C in a furnace under nitrogen gas
for 1 h. The IG/ID ratio calculated from the Raman study increases with the
increasing of the degree of the graphitization in the order of rGO from oil palm
leaves (rGOOPL) < rGO palm kernel shells (rGOPKS) < rGO commercial graphite
(rGOCG) < rGO empty fruit bunches (rGOEFB) with the IG/ID values of 1.06, 1.14,
1.16 and 1.20, respectively. The surface area and pore volume analyses of the as
prepared materials were performed using the Brunauer Emmett Teller-Nitrogen (BET
N2) adsorption-desorption isotherms method. The lower BET surface area of 8 and
15 m2 g-1 observed for rGOCG and rGOOPL, respectively could be due to partial
restacking of GO layers and locally-blocked pores. Relatively, this lower BET
surface area is inconsequential when compared to rGOPKS and rGOEFB, which have a
surface area of 114 and 117 m2 g-1, respectively.
PMID- 28703758
TI - Use of a Mobile Application for Self-Monitoring Dietary Intake: Feasibility Test
and an Intervention Study.
AB - Given the increasing social and economic burden of chronic disease and the need
for efficient approaches to prevent and treat chronic disease, emphasis on the
use of information and communication technology (ICT)-based health care has
emerged. We aimed to test the feasibility of a mobile application, Diet-A, and
examine whether Diet-A could be used to monitor dietary intake among adolescents.
In a three-month pre-post intervention study, 9 male and 24 female high school
students aged 16-18 years consented and participated in this study. Participants
were instructed to record all foods and beverages consumed using voice or text
mode input. Nutrient intake was measured using 24-h recalls pre- and post
intervention. We compared nutrient intake data assessed by Diet-A application
with those assessed by 24-h recalls. Participants tended to underreport intakes
of nutrients compared to those assessed by two 24-h recalls. There were
significant decreases in sodium (p = 0.04) and calcium (p = 0.03) intake between
pre- and post-intervention. Of participants who completed questionnaires of
feasibility (n = 24), 61.9% reported that they were satisfied using the
application to monitor their food intake, and 47.7% liked getting personal
information about their dietary intake from the application. However, more than
70% of participants answered that it was burdensome to use the application or
that they had trouble remembering to record their food intake. The mobile
application Diet-A offers the opportunity to monitor dietary intake through real
time feedback. However, use of Diet-A may not provide accurate information on the
food intake of adolescents, partly because of the recording burden.
PMID- 28703759
TI - Dietary Supplementation of Fermented Rice Bran Effectively Alleviates Dextran
Sodium Sulfate-Induced Colitis in Mice.
AB - Rice bran (RB) is a major by-product of rice polishing and a rich source of
bioactive compounds. Here, we investigated the anti-colitis effect of diet
supplementation with fermented rice bran (FRB) in a murine model of ulcerative
colitis. FRB was prepared by dual fermentation of RB using fungi and lactic acid
bacteria. Colitis was induced in C57Bl/6N male mice (n = 8/group) by dextran
sodium sulfate (DSS). Body weight change, disease activity index (DAI),
histopathology score, tissue myeloperoxidase (MPO) activity, cytokine and
chemokine transcript levels, and the production of short-chain fatty acids
(SCFAs) and mucin in the colonic tissue were monitored. Based on histopathology
scores, DSS induced severe mucosal inflammation, with an increased loss of
crypts, and inflammatory cell infiltration in the control and RB groups, but not
in the FRB group. MPO activity, thiobarbituric acid-reactive substance levels,
and pro-inflammatory cytokine transcript (Tnf-alpha, Il-1beta, Il-6, and Il-17)
levels were significantly higher in the control and RB groups than in the FRB
group. Thus, dietary FRB attenuated intestinal inflammation owing to elevated
SCFAs and tryptamine production, which might regulate tight junction barrier
integrity and intestinal homeostasis. These results suggest that FRB could
comprise an effective potential preventive agent for ulcerative colitis.
PMID- 28703760
TI - The Regular Interaction Pattern among Odorants of the Same Type and Its
Application in Odor Intensity Assessment.
AB - The olfactory evaluation function (e.g., odor intensity rating) of e-nose is
always one of the most challenging issues in researches about odor pollution
monitoring. But odor is normally produced by a set of stimuli, and odor
interactions among constituents significantly influenced their mixture's odor
intensity. This study investigated the odor interaction principle in odor
mixtures of aldehydes and esters, respectively. Then, a modified vector model
(MVM) was proposed and it successfully demonstrated the similarity of the odor
interaction pattern among odorants of the same type. Based on the regular
interaction pattern, unlike a determined empirical model only fit for a specific
odor mixture in conventional approaches, the MVM distinctly simplified the odor
intensity prediction of odor mixtures. Furthermore, the MVM also provided a way
of directly converting constituents' chemical concentrations to their mixture's
odor intensity. By combining the MVM with usual data-processing algorithm of e
nose, a new e-nose system was established for an odor intensity rating. Compared
with instrumental analysis and human assessor, it exhibited accuracy well in both
quantitative analysis (Pearson correlation coefficient was 0.999 for individual
aldehydes (n = 12), 0.996 for their binary mixtures (n = 36) and 0.990 for their
ternary mixtures (n = 60)) and odor intensity assessment (Pearson correlation
coefficient was 0.980 for individual aldehydes (n = 15), 0.973 for their binary
mixtures (n = 24), and 0.888 for their ternary mixtures (n = 25)). Thus, the
observed regular interaction pattern is considered an important foundation for
accelerating extensive application of olfactory evaluation in odor pollution
monitoring.
PMID- 28703761
TI - A Wi-Fi Union Mechanism for Internet Advertising Reciprocal Platform in
Microenterprises.
AB - With the evolution of the Internet and smartphone devices, Internet advertising
has become one of the most important methods for delivering promotional marketing
messages to customers. However, the efficiency of Internet advertising for
microenterprise is not very high, since Wi-Fi advertising-which is limited by a
small router coverage area-is mainly used. Moreover, because of the lack of
money, microenterprises have been using low-cost methods to promote their
products. Thus, enhancing the effectiveness of Wi-Fi advertising, and solving the
problem of cost and the range of the views are now an essential investigation in
this study. In this paper, we propose a reciprocal model with Wi-Fi union
mechanism for Internet advertising based on fog computing architecture to enhance
the efficiency of advertisement, reduce the cost, and increase the range of the
views for microenterprise by using the Internet. In particular, the system was
built in advertisers', publishers', and consumers' sides. In our system, we use
contribution point (CP) as an exchange value among the participants. Advertisers
and publishers can get CP by helping the others in the system to promote their
advertisements, increasing their CP by one unit. Similarly, advertisers and
publishers can use their CP to ask for assistance from the others, decreasing
their CP by one unit. The result shows that the system in a Wi-Fi union is easy
to use, and advertisements can be seen by all customers who are using free Wi-Fi
from the stores of the union. This method can solve the problem of cost and fixed
consumer groups.
PMID- 28703762
TI - Ultrafast Dynamics of Sb-Corroles: A Combined Vis-Pump Supercontinuum Probe and
Broadband Fluorescence Up-Conversion Study.
AB - Corroles are a developing class of tetrapyrrole-based molecules with significant
chemical potential and relatively unexplored photophysical properties. We
combined femtosecond broadband fluorescence up-conversion and fs broadband Vis
pump Vis-probe spectroscopy to comprehensively characterize the photoreaction of
5,10,15-tris-pentafluorophenyl-corrolato-antimony(V)-trans-difluoride (Sb-tpfc
F2). Upon fs Soret band excitation at ~400 nm, the energy relaxed almost
completely to Q band electronic excited states with a time constant of 500 +/-
100 fs; this is evident from the decay of Soret band fluorescence at around 430
nm and the rise time of Q band fluorescence, as well as from Q band stimulated
emission signals at 600 and 650 nm with the same time constant. Relaxation
processes on a time scale of 10 and 20 ps were observed in the fluorescence and
absorption signals. Triplet formation showed a time constant of 400 ps, with an
intersystem crossing yield from the Q band to the triplet manifold of between 95%
and 99%. This efficient triplet formation is due to the spin-orbit coupling of
the antimony ion.
PMID- 28703763
TI - A Chemist's Perspective on the Role of Phosphorus at the Origins of Life.
AB - The central role that phosphates play in biological systems, suggests they also
played an important role in the emergence of life on Earth. In recent years,
numerous important advances have been made towards understanding the influence
that phosphates may have had on prebiotic chemistry, and here, we highlight two
important aspects of prebiotic phosphate chemistry. Firstly, we discuss prebiotic
phosphorylation reactions; we specifically contrast aqueous electrophilic
phosphorylation, and aqueous nucleophilic phosphorylation strategies, with dry
state phosphorylations that are mediated by dissociative phosphoryl-transfer.
Secondly, we discuss the non-structural roles that phosphates can play in
prebiotic chemistry. Here, we focus on the mechanisms by which phosphate has
guided prebiotic reactivity through catalysis or buffering effects, to
facilitating selective transformations in neutral water. Several prebiotic routes
towards the synthesis of nucleotides, amino acids, and core metabolites, that
have been facilitated or controlled by phosphate acting as a general acid-base
catalyst, pH buffer, or a chemical buffer, are outlined. These facile and subtle
mechanisms for incorporation and exploitation of phosphates to orchestrate
selective, robust prebiotic chemistry, coupled with the central and universally
conserved roles of phosphates in biochemistry, provide an increasingly clear
message that understanding phosphate chemistry will be a key element in
elucidating the origins of life on Earth.
PMID- 28703764
TI - Erythropoietin and Its Angiogenic Activity.
AB - Erythropoietin (EPO) is the main hematopoietic hormone acting on progenitor red
blood cells via stimulation of cell growth, differentiation, and anti-apoptosis.
However, its receptor (EPOR) is also expressed in various non-hematopoietic
tissues, including endothelium. EPO is a pleiotropic growth factor that exhibits
growth stimulation and cell/tissue protection on numerous cells and tissues. In
this article we review the angiogenesis potential of EPO on endothelial cells in
heart, brain, and leg ischemia, as well as its role in retinopathy protection and
tumor promotion. Furthermore, the effect of EPO on bone marrow and adipose tissue
is also discussed.
PMID- 28703765
TI - Anti-Biofilm Effect of Biodegradable Coatings Based on Hemibastadin Derivative in
Marine Environment.
AB - Dibromohemibastadin-1 (DBHB) is an already known potent inhibitor of blue mussel
phenoloxidase (which is a key enzyme involved in bioadhesion). Within this study,
the potentiality of DBHB against microfouling has been investigated. The activity
of DBHB was evaluated on key strains of bacteria and microalgae involved in
marine biofilm formation and bioassays assessing impact on growth, adhesion and
biofilm formation were used. To assess the efficiency of DBHB when included in a
matrix, DBHB varnish was prepared and the anti-microfouling activity of coatings
was assessed. Both in vitro and in situ immersions were carried out. Confocal
Laser Scanning Microscopy (CLSM) was principally used to determine the biovolume
and average thickness of biofilms developed on the coatings. Results showed an
evident efficiency of DBHB as compound and varnish to reduce the biofilm
development. The mode of action seems to be based principally on a perturbation
of biofilm formation rather than on a biocidal activity in the tested conditions.
PMID- 28703766
TI - Synthesis and In Vitro Antimycobacterial and Antibacterial Activity of 8-OMe
Ciprofloxacin-Hydrozone/Azole Hybrids.
AB - A series of novel 8-OMe ciprofloxacin (CPFX)-hydrazone/azole hybrids were
designed, synthesized, and evaluated for their in vitro biological activities.
Our results reveal that all of the hydrozone-containing hybrids (except for 7)
show potency against Mycobacterium tuberculosis (MTB) H37Rv (minimum inhibitory
concentration (MIC): <0.5 MUM), which is better than the parent drug CPFX, and
comparable to moxifloxacin and isoniazid, some of the tested Gram-positive
strains (MIC: 0.06-4 MUg/mL), and most Gram-negative strains (MIC: <=0.03-4
MUg/mL).
PMID- 28703767
TI - Co-Transcriptional Folding and Regulation Mechanisms of Riboswitches.
AB - Riboswitches are genetic control elements within non-coding regions of mRNA.
These self-regulatory elements have been found to sense a range of small
metabolites, ions, and other physical signals to exert regulatory control of
transcription, translation, and splicing. To date, more than a dozen riboswitch
classes have been characterized that vary widely in size and secondary structure.
Extensive experiments and theoretical studies have made great strides in
understanding the general structures, genetic mechanisms, and regulatory
activities of individual riboswitches. As the ligand-dependent co-transcriptional
folding and unfolding dynamics of riboswitches are the key determinant of gene
expression, it is important to investigate the thermodynamics and kinetics of
riboswitches both in the presence and absence of metabolites under the
transcription. This review will provide a brief summary of the studies about the
regulation mechanisms of the pbuE, SMK, yitJ, and metF riboswitches based on the
ligand-dependent co-transcriptional folding of the riboswitches.
PMID- 28703768
TI - Stroke Mortality Attributable to Ambient Particulate Matter Pollution from 1990
to 2015 in China: An Age-Period-Cohort and Spatial Autocorrelation Analysis.
AB - In this study, we analyzed the temporal and spatial variations of stroke
mortality attributable to ambient particulate matter pollution (stroke mortality
PM2.5) in China from 1990 to 2015. Data were collected from the Global Burden of
Disease (GBD) 2015 study and analyzed by an age-period-cohort model (APC) with an
intrinsic estimator (IE) algorithm, as well as spatial autocorrelation based on
the Geographic Information System. Based on APC analysis with the IE method,
stroke mortality-PM2.5 increased exponentially with age, its relative risk
reaching 42.85 (95% CI: 28.79, 63.43) in the 75-79 age group. The period effects
showed a reversed V-shape and its highest relative risk was 1.22 (95% CI: 1.15,
1.27) in 2005. The cohort effects decreased monotonically from 1915-1919 to 1990
1994. The change rate fluctuated from 1920-1924 to 1990-1994, including three
accelerating and three decelerating decreases. There was a positive spatial
autocorrelation in stroke mortality-PM2.5 from 1990 to 2015. Hot-spots moved from
the northeastern areas to the middle and southwestern areas, whereas cold-spots
lay mostly in coastal provinces. Besides the aging process in recent years,
stroke mortality-PM2.5 had significantly declined from 2005 to 2015 due to socio
economic and healthcare development. Stroke mortality-PM2.5 varied substantially
among different regions, and cost-effective prevention and control should be
implemented more in the middle and southwestern areas of China.
PMID- 28703769
TI - Glycosaminoglycans Regulate CXCR3 Ligands at Distinct Levels: Protection against
Processing by Dipeptidyl Peptidase IV/CD26 and Interference with Receptor
Signaling.
AB - CXC chemokine ligand (CXCL)9, CXCL10 and CXCL11 direct chemotaxis of mainly T
cells and NK cells through activation of their common CXC chemokine receptor
(CXCR)3. They are inactivated upon NH2-terminal cleavage by dipeptidyl peptidase
IV/CD26. In the present study, we found that different glycosaminoglycans (GAGs)
protect the CXCR3 ligands against proteolytic processing by CD26 without directly
affecting the enzymatic activity of CD26. In addition, GAGs were shown to
interfere with chemokine-induced CXCR3 signaling. The observation that heparan
sulfate did not, and heparin only moderately, altered CXCL10-induced T cell
chemotaxis in vitro may be explained by a combination of protection against
proteolytic inactivation and altered receptor interaction as observed in calcium
assays. No effect of CD26 inhibition was found on CXCL10-induced chemotaxis in
vitro. However, treatment of mice with the CD26 inhibitor sitagliptin resulted in
an enhanced CXCL10-induced lymphocyte influx into the joint. This study reveals a
dual role for GAGs in modulating the biological activity of CXCR3 ligands. GAGs
protect the chemokines from proteolytic cleavage but also directly interfere with
chemokine-CXCR3 signaling. These data support the hypothesis that both GAGs and
CD26 affect the in vivo chemokine function.
PMID- 28703770
TI - Exposure to Engineered Nanomaterials: Impact on DNA Repair Pathways.
AB - Some engineered nanomaterials (ENMs) may have the potential to cause damage to
the genetic material in living systems. The mechanistic machinery functioning at
the cellular/molecular level, in the form of DNA repair processes, has evolved to
help circumvent DNA damage caused by exposure to a variety of foreign substances.
Recent studies have contributed to our understanding of the various DNA damage
repair pathways involved in the processing of DNA damage. However, the vast array
of ENMs may present a relatively new challenge to the integrity of the human
genome; therefore, the potential hazard posed by some ENMs necessitates the
evaluation and understanding of ENM-induced DNA damage repair pathways. This
review focuses on recent studies highlighting the differential regulation of DNA
repair pathways, in response to a variety of ENMs, and discusses the various
factors that dictate aberrant repair processes, including intracellular
signalling, spatial interactions and ENM-specific responses.
PMID- 28703772
TI - Understanding the Inguinal Sinus in Sheep (Ovis aries)-Morphology, Secretion, and
Expression of Progesterone, Estrogens, and Prolactin Receptors.
AB - Post-parturient behavior of mammalian females is essential for early parent
offspring contact. After delivery, lambs need to ingest colostrum for obtaining
the related immunological protection, and early interactions between the mother
and the lamb are crucial. Despite visual and auditory cues, olfactory cues are
decisive in lamb orientation to the mammary gland. In sheep, the inguinal sinus
is located bilaterally near the mammary gland as a skin pouch (IGS) that presents
a gland that secretes a strong-smelling wax. Sheep IGS gland functions have many
aspects under evaluation. The objective of the present study was to evaluate
sheep IGS gland functional aspects and mRNA transcription and the protein
expression of several hormone receptors, such as progesterone receptor (PGR),
estrogen receptor 1 (ESR1), and 2 (ESR2) and prolactin receptor (PRLR) present.
In addition, another aim was to achieve information about IGS ultrastructure and
chemical compounds produced in this gland. All hormone receptors evaluated show
expression in IGS during the estrous cycle (follicular/luteal phases), pregnancy,
and the post-partum period. IGS secretion is rich in triterpenoids that totally
differ from the surrounding skin. They might be essential substances for the
development of an olfactory preference of newborns to their mothers.
PMID- 28703771
TI - Vertebrate Reservoirs of Arboviruses: Myth, Synonym of Amplifier, or Reality?
AB - The rapid succession of the pandemic of arbovirus diseases, such as dengue, West
Nile fever, chikungunya, and Zika fever, has intensified research on these and
other arbovirus diseases worldwide. Investigating the unique mode of vector-borne
transmission requires a clear understanding of the roles of vertebrates. One
major obstacle to this understanding is the ambiguity of the arbovirus definition
originally established by the World Health Organization. The paucity of pertinent
information on arbovirus transmission at the time contributed to the notion that
vertebrates played the role of reservoir in the arbovirus transmission cycle.
Because this notion is a salient feature of the arbovirus definition, it is
important to reexamine its validity. This review addresses controversial issues
concerning vertebrate reservoirs and their role in arbovirus persistence in
nature, examines the genesis of the problem from a historical perspective,
discusses various unresolved issues from multiple points of view, assesses the
present status of the notion in light of current knowledge, and provides options
for a solution to resolve the issue.
PMID- 28703773
TI - An Analysis of Anxiety-Related Postings on Sina Weibo.
AB - This study examines anxiety-related postings on Sina Weibo to gain insight into
social networking about mental health. The themes of a random sample of anxiety
related postings (n = 1000) were assessed. The disclosure of anxiety was the most
common theme. The prevalence of anxiety was higher in certain areas where the
economy is stronger than others, and the people living there suffered from more
stress. Users who talked about feeling anxious tended to be more active on social
media during leisure hours and less active during work hours. Our findings may be
developed to detect and help individuals who may suffer from anxiety disorders at
a low cost.
PMID- 28703775
TI - Novel Applications of Metabolomics in Personalized Medicine: A Mini-Review.
AB - Interindividual variability in drug responses and disease susceptibility is
common in the clinic. Currently, personalized medicine is highly valued, the idea
being to prescribe the right medicine to the right patient. Metabolomics has been
increasingly applied in evaluating the therapeutic outcomes of clinical drugs by
correlating the baseline metabolic profiles of patients with their responses,
i.e., pharmacometabonomics, as well as prediction of disease susceptibility among
population in advance, i.e., patient stratification. The accelerated advance in
metabolomics technology pinpoints the huge potential of its application in
personalized medicine. In current review, we discussed the novel applications of
metabolomics with typical examples in evaluating drug therapy and patient
stratification, and underlined the potential of metabolomics in personalized
medicine in the future.
PMID- 28703774
TI - Programmed Cell Death 1 (PD-1) and Cytotoxic T Lymphocyte-Associated Antigen 4
(CTLA-4) in Viral Hepatitis.
AB - Virus-specific cluster of differentiation 8 (CD8+) cytotoxic T cells (CTL)
recognize viral antigens presented on major histocompatibility complex (MHC)
class I chains on infected hepatocytes, with help from CD4+ T cells. However,
this CTL response is frequently weak or undetectable in patients with chronic
hepatitis B virus (HBV) and hepatitis C virus (HCV) infection. Programmed cell
death 1 (PD-1) and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) are
receptors in the CD28 family of costimulatory molecules, providing inhibitory
signals to T cells. The overexpressions of PD-1 and CTLA-4 in patients with viral
infection have been shown to associate with functional impairment of virus
specific T cells. In acute viral hepatitis, PD-1 and CTLA-4 are up-regulated
during the symptomatic phase, and then down-regulated after recovery. These
findings suggest that PD-1 and CTLA-4 have protective effects as inhibitory
molecules to suppress cytotoxic T cells which induce harmful destruction of viral
infected hepatocytes in self-limited viral hepatitis. In chronic viral hepatitis,
the extended upregulations of PD-1 and CTLA-4 are associated with T cell
exhaustion and persistent viral infection, suggesting positive correlations
between expression of immune inhibitory factors and the chronicity of viral
disease. In this review, we summarize recent literature relating to PD-1, CTLA-4,
and other inhibitory receptors in antigen-specific T cell exhaustion in viral
hepatitis, including hepatitis A, B, C, and others.
PMID- 28703776
TI - Biodegradable and Petroleum-Based Microplastics Do Not Differ in Their Ingestion
and Excretion but in Their Biological Effects in a Freshwater Invertebrate
Gammarus fossarum.
AB - Research on the uptake and effects of bioplastics by aquatic organisms is still
in its infancy. Here, we aim to advance the field by comparing uptake and effects
of microplastic particles (MPP) of a biodegradable bioMPP (polyhydroxybutyrate
(PHB)) and petroleum-based MPP (polymethylmethacrylate (PMMA)) in the freshwater
amphipod Gammarus fossarum. Ingestion of both MPP in different particle sizes (32
250 um) occurred after 24 h, with highest ingestion of particles in the range 32
63 um and almost complete egestion after 64 h. A four-week effect-experiment
showed a significant decrease of the assimilation efficiency in amphipods exposed
to the petroleum-based MPP from week two onwards. The petroleum-based PMMA
affected assimilation efficiency significantly in contrast to the biodegradable
PHB, but overall differences in direct comparison of MPP types were small. Both
MPP types led to a significantly lower wet weight gain relative to the control
treatments. After four weeks, differences between both MPP types and silica, used
as a natural particle control, were detected. In summary, these results suggest
that both MPP types provoke digestive constraints on the amphipods, which go
beyond those of natural non-palatable particles. This highlights the need for
more detailed research comparing environmental effects of biodegradable and
petroleum-based MPP and testing those against naturally occurring particle loads.
PMID- 28703777
TI - Physiological Effects of Touching Coated Wood.
AB - This study examined the physiological effects of touching wood with various
coating with the palm of the hand on brain activity and autonomic nervous
activity. Participants were 18 female university students (mean age, 21.7 +/- 1.6
years). As an indicator of brain activity, oxyhemoglobin concentrations were
measured in the left and right prefrontal cortices using near-infrared time
resolved spectroscopy. Heart rate variability (HRV) and heart rate were used as
indicators of autonomic nervous activity. The high-frequency (HF) component of
HRV, which reflects parasympathetic nervous activity, and the low-frequency
(LF)/HF ratio, which reflects sympathetic nervous activity, were measured. Plates
of uncoated, oil-finished, vitreous-finished, urethane-finished, and mirror
finished white oak wood were used as tactile stimuli. After sitting at rest with
their eyes closed for 60 s, participants touched the stimuli with their palm for
90 s each. The results indicated that tactile stimulation with uncoated wood
calmed prefrontal cortex activity (vs. urethane finish and mirror finish),
increased parasympathetic nervous activity (vs. vitreous finish, urethane finish,
and mirror finish), and decreased heart rate (vs. mirror finish), demonstrating a
physiological relaxation effect. Further, tactile stimulation with oil- and
vitreous-finished wood calmed left prefrontal cortex activity and decreased heart
rate relative to mirror-finished wood.
PMID- 28703778
TI - Natural Product Discovery Using Planes of Principal Component Analysis in R
(PoPCAR).
AB - Rediscovery of known natural products hinders the discovery of new, unique
scaffolds. Efforts have mostly focused on streamlining the determination of what
compounds are known vs. unknown (dereplication), but an alternative strategy is
to focus on what is different. Utilizing statistics and assuming that common
actinobacterial metabolites are likely known, focus can be shifted away from
dereplication and towards discovery. LC-MS-based principal component analysis
(PCA) provides a perfect tool to distinguish unique vs. common metabolites, but
the variability inherent within natural products leads to datasets that do not
fit ideal standards. To simplify the analysis of PCA models, we developed a
script that identifies only those masses or molecules that are unique to each
strain within a group, thereby greatly reducing the number of data points to be
inspected manually. Since the script is written in R, it facilitates integration
with other metabolomics workflows and supports automated mass matching to
databases such as Antibase.
PMID- 28703779
TI - Development of Phosphorothioate DNA and DNA Thioaptamers.
AB - Nucleic acid aptamers are short RNA- or DNA-based affinity reagents typically
selected from combinatorial libraries to bind to a specific target such as a
protein, a small molecule, whole cells or even animals. Aptamers have utility in
the development of diagnostic, imaging and therapeutic applications due to their
size, physico-chemical nature and ease of synthesis and modification to suit the
application. A variety of oligonucleotide modifications have been used to enhance
the stability of aptamers from nuclease degradation in vivo. The non-bridging
oxygen atoms of the phosphodiester backbones of RNA and DNA aptamers can be
substituted with one or two sulfur atoms, resulting in thioaptamers with
phosphorothioate or phosphorodithioate linkages, respectively. Such thioaptamers
are known to have increased binding affinity towards their target, as well as
enhanced resistance to nuclease degradation. In this review, we discuss the
development of phosphorothioate chemistry and thioaptamers, with a brief review
of selection methods.
PMID- 28703780
TI - In Vitro and In Vivo Control of Secondary Bacterial Infection Caused by
Leishmania major.
AB - Bacterial infections of cutaneous leishmaniasis cause skin ulcers on mice,
resulting in increased tissue deterioration, and these infections can be
controlled with liquid allicin. To isolate and identify the incidences of real
secondary bacterial infections in mice, we performed the current study by
injecting mice (n = 50) with Leishmania major. L. major infections were initiated
by an intramuscular injection of 0.1 mL Roswell Park Memorial Institute (RPMI
1640 media/mouse (107 promastigote/mL)). Scarring appeared 2-6 weeks after
injection, and the bacteria were isolated from the skin ulcer tissues. Allicin
(50 uL/mL) and ciprofloxacin (5 MUg; Cip 5) were used for controlling L. major
and bacteria. One hundred samples from skin ulcers of mice were examined, and 200
bacterial colonies were isolated. Forty-eight different genera and species were
obtained and identified by Gram staining and physiological and biochemical
characterization using identification kits. All samples were positive for
secondary bacterial infections. Of the isolates, 79.16% were identified as Gram
negative bacteria, and 28.84% were identified as Gram-positive bacteria; only one
yeast species was found. Interestingly, pure allicin liquid at a concentration 50
uL/mL exhibited antibacterial activity against a wide range of Gram-negative and
some Gram-positive bacteria, in addition to yeast, and was 71.43% effective.
Antimicrobial resistance patterns of all genera and species were determined using
15 different antibiotics. Allicin (50 uL/mL) and Cip 5 were the most effective
against L. major and 92.30% of isolated bacteria. Stenotrophomonas maltophilia
was the most resistant bacterium to the tested antibiotics with a survival rate
of 73.33%, and it exhibited resistance to allicin.
PMID- 28703781
TI - Investigation, Pollution Mapping and Simulative Leakage Health Risk Assessment
for Heavy Metals and Metalloids in Groundwater from a Typical Brownfield, Middle
China.
AB - Heavy metal and metalloid (Cr, Pb, Cd, Zn, Cu, Ni, As and Hg) concentrations in
groundwater from 19 typical sites throughout a typical brownfield were detected.
Mean concentrations of toxic metals in groundwater decreased in the order of Cr >
Zn > Cu > Cd > Ni > Pb > Hg > As. Concentration of Cr6+ in groundwater was
detected to further study chromium contamination. Cr6+ and Cd in groundwater were
recommended as the priority pollutants because they were generally 1399-fold and
12-foldgreater than permissible limits, respectively. Owing to the fact that a
waterproof curtain (WPC) in the brownfield is about to pass the warranty period,
a steady two-dimensional water quality model and health risk assessment were
applied to simulate and evaluate adverse effects of Cr6 + and Cd on the water
quality of Xiangjiang River and the drinking-water intake of Wangcheng
Waterworks. The results indicated that when groundwater in the brownfield leaked
with valid curtain prevention, the water quality in Xiangjiang River and drinking
water intake downstream were temporarily unaffected. However, if there was no
curtain prevention, groundwater leakage would have adverse impact on water
quality of Xiangjiang River. Under the requirements of Class III surface water
quality, the pollution belt for Cr6+ was 7500 m and 200 m for Cd. The non
carcinogenic risk of toxic metals in Xiangjiang River exceeded the threshold in a
limited area, but did not threaten Wangcheng Waterworks. By contrast, the
carcinogenic risk area for adults was at a transverse distance of 200 m and a
longitudinal distance of 18,000 m, which was close to the Wangcheng Waterworks
(23,000 m). Therefore, it was essential to reconstruct the WPC in the brownfield
for preventing pollution diffusion.
PMID- 28703783
TI - Facile Synthesis of Novel Coumarin Derivatives, Antimicrobial Analysis, Enzyme
Assay, Docking Study, ADMET Prediction and Toxicity Study.
AB - The work reports the synthesis under solvent-free condition using the ionic
liquid [Et3NH][HSO4] as a catalyst of fifteen novel 3
((dicyclohexylamino)(substituted phenyl/heteryl)-methyl)-4-hydroxy-2H-chromen-2
onederivatives 4a-o as potential antimicrobial agents. The structures of the
synthesized compounds were confirmed by IR, 1H-NMR, 13C-NMR, mass spectral
studies and elemental analyses. All the synthesized compounds were evaluated for
their in vitro antifungal and antibacterial activity. The compound 4k bearing 4
hydroxy-3-ethoxy group on the phenyl ring was found to be the most active
antifungal agent. The compound 4e bearing a 2,4-difluoro group on the phenyl ring
was found to be the most active antibacterial agent. The mode of action of the
most promising antifungal compound 4k was established by an ergosterol extraction
and quantitation assay. From the assay it was found that 4k acts by inhibition of
ergosterol biosynthesis in C. albicans. Molecular docking studies revealed a
highly spontaneous binding ability of the tested compounds to the active site of
lanosterol 14alpha-demethylase, which suggests that the tested compounds inhibit
the synthesis of this enzyme. The synthesized compounds were analyzed for in
silico ADMET properties to establish oral drug like behavior and showed
satisfactory results. To establish the antimicrobial selectivity and safety, the
most active compounds 4e and 4k were further tested for cytotoxicity against
human cancer cell line HeLa and were found to be non-cytotoxic in nature. An in
vivo acute oral toxicity study was also performed for the most active compounds
4e and 4k and results indicated that the compounds are non-toxic.
PMID- 28703782
TI - Understanding the Role of Non-Coding RNAs in Bladder Cancer: From Dark Matter to
Valuable Therapeutic Targets.
AB - The mortality and morbidity that characterize bladder cancer compel this
malignancy into the category of hot topics in terms of biomolecular research.
Therefore, a better knowledge of the specific molecular mechanisms that underlie
the development and progression of bladder cancer is demanded. Tumor
heterogeneity among patients with similar diagnosis, as well as intratumor
heterogeneity, generates difficulties in terms of targeted therapy. Furthermore,
late diagnosis represents an ongoing issue, significantly reducing the response
to therapy and, inevitably, the overall survival. The role of non-coding RNAs in
bladder cancer emerged in the last decade, revealing that microRNAs (miRNAs) may
act as tumor suppressor genes, respectively oncogenes, but also as biomarkers for
early diagnosis. Regarding other types of non-coding RNAs, especially long non
coding RNAs (lncRNAs) which are extensively reviewed in this article, their exact
roles in tumorigenesis are-for the time being-not as evident as in the case of
miRNAs, but, still, clearly suggested. Therefore, this review covers the non
coding RNA expression profile of bladder cancer patients and their validated
target genes in bladder cancer cell lines, with repercussions on processes such
as proliferation, invasiveness, apoptosis, cell cycle arrest, and other molecular
pathways which are specific for the malignant transformation of cells.
PMID- 28703784
TI - Targeting Pattern Recognition Receptors (PRR) for Vaccine Adjuvantation: From
Synthetic PRR Agonists to the Potential of Defective Interfering Particles of
Viruses.
AB - Modern vaccinology has increasingly focused on non-living vaccines, which are
more stable than live-attenuated vaccines but often show limited immunogenicity.
Immunostimulatory substances, known as adjuvants, are traditionally used to
increase the magnitude of protective adaptive immunity in response to a pathogen
associated antigen. Recently developed adjuvants often include substances that
stimulate pattern recognition receptors (PRRs), essential components of innate
immunity required for the activation of antigen-presenting cells (APCs), which
serve as a bridge between innate and adaptive immunity. Nearly all PRRs are
potential targets for adjuvants. Given the recent success of toll-like receptor
(TLR) agonists in vaccine development, molecules with similar, but additional,
immunostimulatory activity, such as defective interfering particles (DIPs) of
viruses, represent attractive candidates for vaccine adjuvants. This review
outlines some of the recent advances in vaccine development related to the use of
TLR agonists, summarizes the current knowledge regarding DIP immunogenicity, and
discusses the potential applications of DIPs in vaccine adjuvantation.
PMID- 28703785
TI - Cerebrospinal Fluid Biomarkers in Alzheimer's Disease-From Brain Starch to Bench
and Bedside.
AB - Alzheimer's disease is the most common cause of dementia. Over the last three
decades, research has advanced dramatically and provided a detailed understanding
of the molecular events underlying the pathogenesis of Alzheimer's disease. In
parallel, assays for the detection of biomarkers that reflect the typical
Alzheimer's disease-associated pathology have been developed and validated in
myriads of clinical studies. Such biomarkers complement clinical diagnosis and
improve diagnostic accuracy. The use of biomarkers will become even more
important with the advent of disease-modifying therapies. Such therapies will
likely be most beneficial when administered early in the disease course. Here, we
summarise the development of the core Alzheimer's disease cerebrospinal fluid
biomarkers: amyloid-beta and tau. We provide an overview of their role in
cellular physiology and Alzheimer's disease pathology, and embed their
development as cerebrospinal fluid biomarkers into the historical context of
Alzheimer's disease research. Finally, we summarise recommendations for their use
in clinical practice, and outline perspectives for novel cerebrospinal fluid
candidate biomarkers.
PMID- 28703786
TI - Fistulizing Crohn's Disease.
AB - Fistulas still represent one of the most important complications in patients with
Crohn's disease (CD). At least one third of CD patients suffer from fistulas
during their disease course and amongst them longstanding remission of complex
fistulas occurs only in about one third. So far, fistula pathogenesis is only
partially understood. From a histopathological view, a fistula is a tube covered
by flat epithelial cells. Current research suggests that the driving force for
fistula development is epithelial-to-mesenchymal transition (EMT). Around the
fistula, high levels of tumor necrosis factor (TNF), IL-13, and TGFbeta can be
detected and recent studies indicated an involvement of the intestinal
microbiota. Fistula diagnosis requires clinical and surgical assessment,
radiologic investigations, e.g., magnet resonance imaging and endoscopy. Routine
medical treatment of fistulas includes antibiotics, immunosuppressives, and anti
TNF antibodies. There is no well-established role for calcineurin inhibitors in
fistula treatment, corticosteroids appear to be even contra-productive. A
promising novel approach might be the application of adipose tissue-derived or
bone marrow-derived mesenchymal stem cells that have been studied recently. Due
to insufficient efficacy of medical treatment and recurrence of fistulas,
surgical interventions are frequently necessary. Further research is needed to
better understand fistula pathogenesis aiming to develop novel treatment option
for our patients.
PMID- 28703787
TI - A new era in the interpretation of human genomic variation.
PMID- 28703788
TI - Preparation of a Trp-BODIPY fluorogenic amino acid to label peptides for enhanced
live-cell fluorescence imaging.
AB - Fluorescent peptides are valuable tools for live-cell imaging because of the high
specificity of peptide sequences for their biomolecular targets. When preparing
fluorescent versions of peptides, labels must be introduced at appropriate
positions in the sequences to provide suitable reporters while avoiding any
impairment of the molecular recognition properties of the peptides. This protocol
describes the preparation of the tryptophan (Trp)-based fluorogenic amino acid
Fmoc-Trp(C2-BODIPY)-OH and its incorporation into peptides for live-cell
fluorescence imaging-an approach that is applicable to most peptide sequences.
Fmoc-Trp(C2-BODIPY)-OH contains a BODIPY (4,4-difluoro-4-bora-3a,4a-diaza-s
indacene) fluorogenic core, which works as an environmentally sensitive
fluorophore, showing high fluorescence in lipophilic conditions. It is attached
to Trp via a spacer-free C-C linkage, resulting in a labeled amino acid that can
mimic the molecular interactions of Trp, enabling wash-free imaging. This
protocol covers the chemical synthesis of the fluorogenic amino acid Fmoc-Trp(C2
BODIPY)-OH (3-4 d), the preparation of the labeled antimicrobial peptide BODIPY
cPAF26 by solid-phase synthesis (6-7 d) and its spectral and biological
characterization as a live-cell imaging probe for different fungal pathogens. As
an example, we include a procedure for using BODIPY-cPAF26 for wash-free imaging
of fungal pathogens, including real-time visualization of Aspergillus fumigatus
(5 d for culturing, 1-2 d for imaging).
PMID- 28703789
TI - Capturing suboptical dynamic structures in lipid bilayer patches formed from free
standing giant unilamellar vesicles.
AB - There is accumulating evidence that the small-scale lateral organization of
biological membranes has a crucial role in signaling and trafficking in cells.
However, it has been difficult to characterize these features with existing
methods for preparing and analyzing freestanding membranes, because the dynamics
occurs below the optical resolution possible with these protocols. We have
developed a protocol that permits the imaging of lipid nanodomains and lateral
protein organization in membranes of giant unilamellar vesicles (GUVs).
Freestanding GUVs are transferred onto a mica support, and after treatment with
magnesium chloride, they collapse to form planar lipid bilayer (PLB) patches.
Rapid GUV collapse onto the mica preserves the lateral organization of
freestanding membranes and thus makes it possible to image 'snapshots' of GUVs up
to nanometer resolution by high-resolution microscopy. The method has been
applied to classical lipid raft mixtures in which suboptical domain fluctuations
have been imaged in both the liquid-ordered and liquid-disordered membrane
phases. High-resolution scanning by atomic force microscopy (AFM) of membranes
composed of binary and ternary lipid mixtures reconstituted with Na+/K+-ATPase
(NKA) has revealed the spatial distribution and orientations of individual
proteins, as well as details of membrane lateral structure. Immunolabeling
followed by confocal microscopy can also provide information about the spatial
distribution of proteins. The protocol opens up a new avenue for quantitative
biophysical studies of suboptical dynamic structures in biomembranes, which are
local and short-lived. Preparation of GUVs, PLB patches and their imaging takes
<24 h.
PMID- 28703790
TI - A fluorescence-based imaging method to measure in vitro and in vivo mitophagy
using mt-Keima.
AB - Mitophagy is a cellular process that selectively removes damaged, old or
dysfunctional mitochondria. Defective mitophagy is thought to contribute to
normal aging and to various neurodegenerative and cardiovascular diseases.
Previous methods used to detect mitophagy in vivo were cumbersome, insensitive
and difficult to quantify. We created a transgenic mouse model that expresses the
pH-dependent fluorescent protein mt-Keima in order to more readily assess
mitophagy. Keima is a pH-sensitive, dual-excitation ratiometric fluorescent
protein that also exhibits resistance to lysosomal proteases. At the
physiological pH of the mitochondria (pH 8.0), the shorter-wavelength excitation
predominates. Within the acidic lysosome (pH 4.5) after mitophagy, mt-Keima
undergoes a gradual shift to longer-wavelength excitation. In this protocol, we
describe how to monitor mitophagic flux in living cells over an 18-h time frame,
as well as how to quantify mitophagy using the mt-Keima probe. This protocol also
describes how to use confocal microscopy to visualize mitophagy in living tissues
obtained from mt-Keima transgenic mice. With this protocol, the mt-Keima probe
can reliably be imaged within the first 60 min after tissue collection. We also
describe how to apply mt-Keima with stimulated emission depletion (STED)
microscopy, which can potentially provide substantially higher-resolution images.
Typically, the approximate time frame for time-lapse fluorescence imaging of mt
Keima is 20 h for living cells. For confocal analysis of tissue from an mt-Keima
mouse, the whole procedure generally takes no longer than 60 min, and the STED
imaging usually takes <2 h.
PMID- 28703793
TI - Linc-DYNC2H1-4 promotes EMT and CSC phenotypes by acting as a sponge of miR-145
in pancreatic cancer cells.
AB - The acquisition of epithelial-mesenchymal transition (EMT) and/or existence of a
sub-population of cancer stem-like cells (CSC) are associated with malignant
behavior and chemoresistance. To identify which factor could promote EMT and CSC
formation and uncover the mechanistic role of such factor is important for novel
and targeted therapies. In the present study, we found that the long intergenic
non-coding RNA linc-DYNC2H1-4 was upregulated in pancreatic cancer cell line BxPC
3-Gem with acquired gemcitabine resistance. Knockdown of linc-DYNC2H1-4 decreased
the invasive behavior of BxPC-3-Gem cells while ectopic expression of linc
DYNC2H1-4 promoted the acquisition of EMT and stemness of the parental sensitive
cells. Linc-DYNC2H1-4 upregulated ZEB1, the EMT key player, which led to
upregulation and downregulation of its targets vimentin and E-cadherin
respectively, as well as enhanced the expressions of CSC makers Lin28, Nanog,
Sox2 and Oct4. Linc-DYNC2H1-4 is mainly located in the cytosol. Mechanically, it
could sponge miR-145 that targets ZEB1, Lin28, Nanog, Sox2, Oct4 to restore these
EMT and CSC-associated genes expressions. We proved that MMP3, the nearby gene of
linc-DYNC2H1-4 in the sense strand, was also a target of miR-145. Downregulation
of MMP3 by miR-145 was reverted by linc-DYNC2H1-4, indicating that competing with
miR-145 is one of the mechanisms for linc-DYNC2H1-4 to regulate MMP3. In summary,
our results explore the important role of linc-DYNC2H1-4 in the acquisition of
EMT and CSC, and the impact it has on gemcitabine resistance in pancreatic cancer
cells.
PMID- 28703794
TI - Impaired autophagosome clearance contributes to neuronal death in a piglet model
of neonatal hypoxic-ischemic encephalopathy.
AB - To examine the temporal relationship of cortical autophagic flux with delayed
neuronal cell death after hypoxia-ischemia (HI) in neonatal piglets. HI was
produced with 45-min hypoxia and 7-min airway occlusion in 3-5-day-old piglets.
Markers of autophagic, lysosomal and cell death signaling were studied via
immunohistochemistry, immunoblotting, and histochemistry in piglet brains. In
vitro, autophagy was impaired in cultured mouse cortical neurons treated with
chloroquine with or without rapamycin for 1 d in the presence of Z-VAD-fmk,
cyclosporine A, or vehicle control, and cell viability was assessed with the MTT
assay. In vivo, neuronal cell death of sensorimotor cortex was delayed by 1-2
days after HI, whereas LC3-II, Beclin-1, PI3KC3, ATG12-ATG-5, and p-ULK1
increased by 1.5-6 h. Autophagosomes accumulated in cortical neurons by 1 d owing
to enhanced autophagy and later to decreased autophagosome clearance, as
indicated by LC3, Beclin-1, and p62 accumulation. Autophagy flux impairment was
attributable to lysosomal dysfunction, as indicated by low lysosomal-associated
membrane protein 2, cathepsin B, and cathepsin D levels at 1 d. Ubiquitin levels
increased at 1 d. Autophagosome and p62 accumulated predominantly in neurons at 1
d, with p62 puncta occurring in affected cells. Beclin-1 colocalized with markers
of caspase-dependent and caspase-independent apoptosis and necrosis in neurons.
In vitro, mouse neonatal cortical neurons treated with rapamycin and chloroquine
showed increased autophagosomes, but not autolysosomes, and increased cell death
that was attenuated by cyclosporine A. Neonatal HI initially increases autophagy
but later impairs autophagosome clearance, coinciding with delayed cortical
neuronal death.
PMID- 28703795
TI - Edaravone suppresses retinal ganglion cell death in a mouse model of normal
tension glaucoma.
AB - Glaucoma, one of the leading causes of irreversible blindness, is characterized
by progressive degeneration of optic nerves and retinal ganglion cells (RGCs). In
the mammalian retina, excitatory amino-acid carrier 1 (EAAC1) is expressed in
neural cells, including RGCs. Loss of EAAC1 leads to RGC degeneration without
elevated intraocular pressure (IOP) and exhibits glaucomatous pathology including
glutamate neurotoxicity and oxidative stress. In the present study, we found that
edaravone, a free radical scavenger that is used for treatment of acute brain
infarction and amyotrophic lateral sclerosis (ALS), reduces oxidative stress and
prevents RGC death and thinning of the inner retinal layer in EAAC1-deficient
(KO) mice. In addition, in vivo electrophysiological analyses demonstrated that
visual impairment in EAAC1 KO mice was ameliorated with edaravone treatment,
clearly establishing that edaravone beneficially affects both histological and
functional aspects of the glaucomatous retina. Our findings raise intriguing
possibilities for the management of glaucoma by utilizing a widely prescribed
drug for the treatment of acute brain infarction and ALS, edaravone, in
combination with conventional treatments to lower IOP.
PMID- 28703796
TI - p75NTR antagonists attenuate photoreceptor cell loss in murine models of
retinitis pigmentosa.
AB - ProNGF signaling through p75NTR has been associated with neurodegenerative
disorders. Retinitis pigmentosa (RP) comprises a group of inherited retinal
dystrophies that causes progressive photoreceptor cell degeneration and death, at
a rate dependent on the genetic mutation. There are more than 300 mutations
causing RP, and this is a challenge to therapy. Our study was designed to explore
a common mechanism for p75NTR in the progression of RP, and assess its potential
value as a therapeutic target. The proNGF/p75NTR system is present in the
dystrophic retina of the rd10 RP mouse model. Compared with wild-type (WT)
retina, the levels of unprocessed proNGF were increased in the rd10 retina at
early degenerative stages, before the peak of photoreceptor cell death.
Conversely, processed NGF levels were similar in rd10 and WT retinas. ProNGF
remained elevated throughout the period of photoreceptor cell loss, correlating
with increased expression of alpha2-macroglobulin, an inhibitor of proNGF
processing. The neuroprotective effect of blocking p75NTR was assessed in
organotypic retinal cultures from rd10 and RhoP mouse models. Retinal explants
treated with p75NTR antagonists showed significantly reduced photoreceptor cell
death, as determined by the terminal deoxynucleotidyl transferase-mediated dUTP
nick-end labeling (TUNEL) assay and by preservation of the thickness of the outer
nuclear layer (ONL), where photoreceptor nuclei are located. This effect was
accompanied by decreased retinal-reactive gliosis and reduced TNFalpha secretion.
Use of p75NTR antagonist THX-B (1,3-diisopropyl-1-[2-(1,3-dimethyl-2,6-dioxo
1,2,3,6-tetrahydro-purin-7-yl)-acetyl]-urea) in vivo in the rd10 and RhoP mouse
models, by a single intravitreal or subconjunctival injection, afforded
neuroprotection to photoreceptor cells, with preservation of the ONL. This study
demonstrates a role of the p75NTR/proNGF axis in the progression of RP, and
validates these proteins as therapeutic targets in two different RP models,
suggesting utility irrespective of etiology.
PMID- 28703797
TI - Dickkopf1 destabilizes atherosclerotic plaques and promotes plaque formation by
inducing apoptosis of endothelial cells through activation of ER stress.
AB - Several clinical studies reported that Dickkopf1 (DKK1) plasma levels are
correlated with atherosclerosis. However, the impact of DKK1 on the formation and
vulnerability of atherosclerotic plaques remains elusive. This study investigated
DKK1's effects on enlargement and destabilization of plaques by targeting
endothelial cells and assessing the possible cellular mechanisms involved. The
effects of DKK1 on atherogenesis and plaque stability were evaluated in ApoE-/-
mice using lentivirus injections to knockdown and knock-in the DKK1 gene. The
presence of DKK1 resulted in enlarged and destabilized atherosclerotic lesions
and increased apoptosis, while silencing of DKK1 alleviated plaque formation and
vulnerability in the whole progression of atherosclerosis. DKK1 expression was
upregulated in response to ox-LDL treatment in a time- and concentration
dependent manner on human umbilical vein endothelial cell (HUVEC). The
interference of DKK1 reversed ox-LDL-induced apoptosis in HUVECs. The mechanism
underlying this effect was DKK1's activation of the JNK signal transduction
pathway and inhibition of canonical Wnt signaling, following by activation of the
IRE1alpha and eif2alpha/CHOP pathways. In conclusion, DKK1 promotes plaque
formation and vulnerability partly by inducing apoptosis in endothelial cells,
which partly through inducing the JNK-endoplasmic reticulum stress pathway and
inhibiting canonical Wnt signaling.
PMID- 28703798
TI - mTORC2 regulates hedgehog pathway activity by promoting stability to Gli2 protein
and its nuclear translocation.
AB - mTORC2 is aberrantly activated in cancer and therefore is considered to be an
important therapeutic target. The hedgehog pathway, which is also often
hyperactivated, regulates transcription of several genes associated with
angiogenesis, metastasis, cellular proliferation and cancer stem cell (CSC)
regeneration. However, the contribution of mTORC2 toward hedgehog pathway
activity has not been explored yet. Here we have addressed the molecular cross
talk between mTORC2 and hedgehog pathway activities in the context of
glioblastoma multiforme, a malignant brain tumor using as a model system. We
observed that higher mTORC2 activity enhanced the expression of a few hedgehog
pathway molecules (Gli1, Gli2 and Ptch1) and amplified its target genes (Cyclin
D1, Cyclin D2, Cyclin E, Snail, Slug and VEGF) both in mRNA and protein levels as
corroborated by increased metastasis, angiogenesis, cellular proliferation and
stem cell regeneration. Inhibition of mTORC2 formation decreased hedgehog pathway
activity and attenuated all these above-mentioned events, suggesting their cross
talk with each other. Further investigations revealed that mTORC2 inhibited
ubiquitination of Gli2 by inactivating GSK3beta, and thus it promotes stability
to Gli2 and its nuclear translocation. Moreover, enhanced mTORC2 activity led to
the increased clonogenic properties and CD133+ cells, indicating its role in CSC
regeneration. mTORC2 inhibitor directed the reduction of hedgehog pathway
proteins and also reduced CSCs. Thus, our observations support a role for
elevated mTORC2 activity in regulating angiogenesis, metastasis, cellular
proliferation and CSC regeneration via hedgehog pathway activity. Taken together,
it provides a rationale for including the mTOR2 inhibitor as part of the
therapeutic regimen for CSCs.
PMID- 28703799
TI - BAG3 promotes stem cell-like phenotype in breast cancer by upregulation of CXCR4
via interaction with its transcript.
AB - BAG3 is an evolutionarily conserved co-chaperone expressed at high levels and has
a prosurvival role in many tumor types. The current study reported that BAG3 was
induced under specific floating culture conditions that enrich breast cancer stem
cell (BCSC)-like cells in spheres. Ectopic BAG3 overexpression increased
CD44+/CD24- CSC subpopulations, first-generation and second-generation
mammosphere formation, indicating that BAG3 promotes CSC self-renewal and
maintenance in breast cancer. We further demonstrated that mechanically, BAG3
upregulated CXCR4 expression at the post-transcriptional level. Further studies
showed that BAG3 interacted with CXCR4 mRNA and promoted its expression via its
coding and 3'-untranslational regions. BAG3 was also found to be positively
correlated with CXCR4 expression and unfavorable prognosis in patients with
breast cancer. Taken together, our data demonstrate that BAG3 promotes BCSC-like
phenotype through CXCR4 via interaction with its transcript. Therefore, this
study establishes BAG3 as a potential adverse prognostic factor and a therapeutic
target of breast cancer.
PMID- 28703800
TI - Killing two birds with one stone: dual blockade of integrin and FGF signaling
through targeting syndecan-4 in postoperative capsular opacification.
AB - The most common complication after cataract surgery is postoperative capsular
opacification, which includes anterior capsular opacification (ACO) and posterior
capsular opacification (PCO). Increased adhesion of lens epithelial cells (LECs)
to the intraocular lens material surface promotes ACO formation, whereas
proliferation and migration of LECs to the posterior capsule lead to the
development of PCO. Cell adhesion is mainly mediated by the binding of integrin
to extracellular matrix proteins, while cell proliferation and migration are
regulated by fibroblast growth factor (FGF). Syndecan-4 (SDC-4) is a co-receptor
for both integrin and FGF signaling pathways. Therefore, SDC-4 may be an ideal
therapeutic target for the prevention and treatment of postoperative capsular
opacification. However, how SDC-4 contributes to FGF-mediated proliferation,
migration, and integrin-mediated adhesion of LECs is unclear. Here, we found that
downregulation of SDC-4 inhibited FGF signaling through the blockade of ERK1/2
and PI3K/Akt/mTOR activation, thus suppressing cell proliferation and migration.
In addition, downregulation of SDC-4 suppressed integrin-mediated cell adhesion
through inhibiting focal adhesion kinase (FAK) phosphorylation. Moreover, SDC-4
knockout mice exhibited normal lens morphology, but had significantly reduced
capsular opacification after injury. Finally, SDC-4 expression level was
increased in the anterior capsule LECs of age-related cataract patients. Taken
together, we for the first time characterized the key regulatory role of SDC-4 in
FGF and integrin signaling in human LECs, and provided the basis for future
pharmacological interventions of capsular opacification.
PMID- 28703801
TI - lncRNA MIAT functions as a competing endogenous RNA to upregulate DAPK2 by
sponging miR-22-3p in diabetic cardiomyopathy.
AB - We previously established a rat model of diabetic cardiomyopathy (DCM) and found
that the expression of long non-coding RNA myocardial infarction-associated
transcript (MIAT) was significantly upregulated. The present study was aimed to
determine the pathologic role of MIAT in the development of DCM. MIAT knockdown
was found to reduce cardiomyocyte apoptosis and improve left ventricular function
in diabetic rats. High glucose could increase MIAT expression and induce
apoptosis in cultured neonatal cardiomyocytes. The results of luciferase reporter
assay and RNA immunoprecipitation assay revealed that MIAT was targeted by miR-22
3p in an AGO2-dependent manner. In addition, the 3'-untranslated region of DAPK2
was fused to the luciferase coding region and transfected into HEK293 cells with
miR-22-3p mimic, and the results showed that DAPK2 was a direct target of miR-22
3p. Our findings also indicated that MIAT overexpression could counteract the
inhibitory effect of miR-22-3p on DAPK2. Moreover, MIAT knockdown was found to
reduce DAPK2 expression and inhibit apoptosis in cardiomyocytes exposed to high
glucose. In conclusion, our study demonstrates that MIAT may function as a
competing endogenous RNA to upregulate DAPK2 expression by sponging miR-22-3p,
which consequently leads to cardiomyocyte apoptosis involved in the pathogenesis
of DCM.
PMID- 28703802
TI - An autocrine inflammatory forward-feedback loop after chemotherapy withdrawal
facilitates the repopulation of drug-resistant breast cancer cells.
AB - Stromal cells, infiltrating immune cells, paracrine factors and extracellular
matrix have been extensively studied in cancers. However, autocrine factors
produced by tumor cells and communications between autocrine factors and
intracellular signaling pathways in the development of drug resistance, cancer
stem-like cells (CSCs) and tumorigenesis have not been well investigated, and the
precise mechanism and tangible approaches remain elusive. Here we reveal a new
mechanism by which cytokines produced by breast cancer cells after chemotherapy
withdrawal activate both Wnt/beta-catenin and NF-kappaB pathways, which in turn
further promote breast cancer cells to produce and secrete cytokines, forming an
autocrine inflammatory forward-feedback loop to facilitate the enrichment of drug
resistant breast cancer cells and/or CSCs. Such an unexpected autocrine forward
feedback loop and CSC enrichment can be effectively blocked by inhibition of
Wnt/beta-catenin and NF-kappaB signaling. It can also be diminished by IL8
neutralizing antibody or blockade of IL8 receptors CXCR1/2 with reparixin.
Administration of reparixin after chemotherapy withdrawal effectively attenuates
tumor masses in a human xenograft model and abolishes paclitaxel-enriched CSCs in
the secondary transplantation. These results are partially supported by the
latest clinical data set. Breast cancer patients treated with chemotherapeutic
drugs exhibited poor survival rate (66.7 vs 282.8 months, P=0.00071) and shorter
disease-free survival time if their tumor samples expressed high level of IL8,
CXCR1, CXCR2 genes and Wnt target genes. Taken together, this study provides new
insights into the communication between autocrine niches and signaling pathways
in the development of chemotherapy resistance and CSCs; it also offers a tangible
approach in breast cancer treatment.
PMID- 28703803
TI - MICU1 protects against myocardial ischemia/reperfusion injury and its control by
the importer receptor Tom70.
AB - Mitochondrial Ca2+ overload is a main contributor to mitochondrial damage hence
cardiomyocyte death in myocardial ischemia/reperfusion (MI/R) injury. MICU1 has
been recently identified as an important regulator of mitochondrial Ca2+
homeostasis. Here we try to identify the role of MICU1 in MI/R, and to
investigate whether the mitochondrial importer receptor Tom70 possesses critical
roles in the mitochondrial translocation of MICU1 and MI/R. Specific small
interfering RNA (20 MUg) against MICU1 and Tom70, and lentivirus vectors carrying
the Tom70a sequences (3.3 * 107 TU) were delivered through intramyocardial
injection. Seventy-two hours after injection, mice were subjected to 30 min of MI
followed by 3 h (for cell apoptosis and mitochondrial damage assessment) or 24 h
(for cardiac function and infarct size determination) of reperfusion. MI/R had no
significant effect on total MICU1 expression, but caused significant reduction of
MICU1 in mitochondria. Knockdown of MICU1 significantly aggravated MI/R injury,
as evidenced by enlarged infarct size, depressed cardiac function and increased
myocardial apoptosis. Moreover, MICU1 deficiency resulted in markedly aggravated
mitochondrial Ca2+ overload, consequently destructed mitochondrial morphology and
suppressed mitochondrial function (evidenced by decreased ATP production).
Interestingly, mitochondrial Tom70 was also decreased in MI/R. Genetic loss
function study revealed that mitochondrial MICU1 expression was depressed by
Tom70 ablation. Furthermore, Tom70 deficiency significantly aggravated MI/R
injury and worsened mitochondrial Ca2+ overload. However, supplementation of
Tom70 significantly attenuated MI/R injury, preserved mitochondrial morphology
and function, and inhibited mitochondrial Ca2+ overload, all of which were
abolished by MICU1 suppression. Mitochondrial Tom70/MICU1 pathway protects
against MI/R injury, in which mitochondrial localization of MICU1 is governed by
Tom70, and MICU1 serves as an indispensable factor in Tom70's cardioprotection.
PMID- 28703804
TI - Pleiotropic effects of sphingosine-1-phosphate signaling to control human
chorionic mesenchymal stem cell physiology.
AB - Chorionic stem cells represent a promising opportunity for regenerative medicine.
A deeper understanding of the stimuli that regulate their physiology, could lead
to innovative clinical approaches. We revealed the presence of multiple
sphingosine-1-phosphate (S1P) receptor isoforms in chorion-derived mesenchymal
stem cells (CMSCs). Their activation simultaneously propagated from the plasma
membrane through Gi and other heterotrimeric G proteins and further diverged
toward extracellular-signal-regulated kinase 1/2 (ERK1/2), p38 and protein kinase
D 1. At a functional level, S1P signaling inhibited CMSC migration, while
promoting proliferation. Instead, a reduction of cell density was obtained when
S1P was combined to treatments that increased cAMP intracellular concentration.
Such surprising reduction of cell viability was relatively specific as it was not
observed with stromal stem cells from bone marrow. Neither it was observed by
activating analogous G proteins with bradykinin nor by inducing cell death via a
cAMP-independent pathway. S1P could thus reveal novel keys to improve CMSC
differentiation programs acting on cAMP concentration. Furthermore, S1P receptor
agonists/antagonists could become instrumental in favoring CMSC engraftment by
controlling cell motility.
PMID- 28703805
TI - Aryl hydrocarbon receptor activation restores filaggrin expression via OVOL1 in
atopic dermatitis.
AB - Filaggrin (FLG) mutation is a well-confirmed genetic aberration in atopic
dermatitis (AD). Genome-wide association studies on AD have revealed other
susceptibility genes, for example, Ovo-like 1 (OVOL1). Nonetheless, the relation
between FLG and OVOL1 is unclear. Because aryl hydrocarbon receptor (AHR; a
ligand-activated transcription factor), plays a role in FLG expression in
keratinocytes, we hypothesized that AHR regulates FLG expression via OVOL1. To
demonstrate this mechanism, we analyzed FLG expression in OVOL1-overexpressing or
OVOL1-knockdown normal human epidermal keratinocytes (NHEKs). Furthermore, we
tested whether AHR activation by 6-formylindolo(3,2-b)carbazole (FICZ), an
endogenous AHR ligand, or Glyteer, clinically used soybean tar, upregulates FLG
and OVOL1 expression in NHEKs. We found that (1) OVOL1 regulates FLG expression;
(2) AHR activation upregulates OVOL1; and (3) AHR activation upregulates FLG via
OVOL1. Moreover, nuclear translocation of OVOL1 was less pronounced in AD skin
compared with normal skin. IL-4-treated NHEKs, an in vitro AD skin model, also
showed inhibition of the OVOL1 nuclear translocation, which was restored by FICZ
and Glyteer. Thus, targeting the AHR-OVOL1-FLG axis may provide new therapeutics
for AD.
PMID- 28703806
TI - Inhibition of autophagy as a treatment strategy for p53 wild-type acute myeloid
leukemia.
AB - Here we have explored whether inhibition of autophagy can be used as a treatment
strategy for acute myeloid leukemia (AML). Steady-state autophagy was measured in
leukemic cell lines and primary human CD34+ AML cells with a large variability in
basal autophagy between AMLs observed. The autophagy flux was higher in AMLs
classified as poor risk, which are frequently associated with TP53 mutations
(TP53mut), compared with favorable- and intermediate-risk AMLs. In addition, the
higher flux was associated with a higher expression level of several autophagy
genes, but was not affected by alterations in p53 expression by knocking down p53
or overexpression of wild-type p53 or p53R273H. AML CD34+ cells were more
sensitive to the autophagy inhibitor hydroxychloroquine (HCQ) than normal bone
marrow CD34+ cells. Similar, inhibition of autophagy by knockdown of ATG5 or ATG7
triggered apoptosis, which coincided with increased expression of p53. In
contrast to wild-type p53 AML (TP53wt), HCQ treatment did not trigger a BAX and
PUMA-dependent apoptotic response in AMLs harboring TP53mut. To further
characterize autophagy in the leukemic stem cell-enriched cell fraction AML CD34+
cells were separated into ROSlow and ROShigh subfractions. The immature AML CD34+
enriched ROSlow cells maintained higher basal autophagy and showed reduced
survival upon HCQ treatment compared with ROShigh cells. Finally, knockdown of
ATG5 inhibits in vivo maintenance of AML CD34+ cells in NSG mice. These results
indicate that targeting autophagy might provide new therapeutic options for
treatment of AML since it affects the immature AML subfraction.
PMID- 28703807
TI - The EGFR/miR-338-3p/EYA2 axis controls breast tumor growth and lung metastasis.
AB - Dysregulation of the epidermal growth factor receptor (EGFR) promotes cancer cell
growth, invasion and metastasis. However, its relevant downstream effectors are
still limited. Here, we show that EGFR promotes breast tumor growth and
metastasis by downregulating the tumor suppressor micoRNA-338-3p (miR-338-3p) and
activating the EYA2 (EYA transcriptional coactivator and phosphatase 2)
oncoprotein. EGFR represses miR-338-3p expression largely through HIF1alpha
transcription factor. miR-338-3p inhibits EYA2 expression by binding to the 3'
untranslated region of EYA2. EGFR increases EYA2 expression via HIF1alpha
repression of miR-338-3p. Through the miR-338-3p/EYA2 pathway, EGFR increases
breast cancer cell growth, epithelial-to-mesenchymal transition, migration,
invasion and lung metastasis in vitro and in a allograft tumor mouse model in
vivo. In breast cancer patients, miR-338-3p expression negatively correlates with
the expression of EGFR and EYA2, EGFR status positively associates with EYA2
expression, and miR-338-3p and EYA2 predict breast cancer lung metastasis when
expressed in primary breast cancers. These data suggest that the miR-338-3p/EYA2
axis contributes to EGFR-mediated tumor growth and lung metastasis and that miR
338-3p activation or EYA2 inhibition or combination therapy targeting EGFR/miR
338-3p/EYA2 axis may be a promising way to treat patients with metastatic cancer.
PMID- 28703808
TI - RIP3 attenuates the pancreatic damage induced by deletion of ATG7.
AB - Invalidation of pancreatic autophagy entails pancreatic atrophy, endocrine and
exocrine insufficiency and pancreatitis. The aim of this study was to investigate
whether depletion of Rip3, which is involved in necroptotic signaling, may
attenuate the pancreatic atrophy and pancreatitis resulting from autophagy
inhibition. Autophagy and necroptosis signaling were evaluated in mice lacking
expression of Rip3 in all organs and Atg7 in the pancreas. Acinar cell death,
inflammation and fibrosis were evaluated by using of a compendium of
immunofluorescence methods and immunoblots. Mice deficient for pancreatic Atg7
developed acute pancreatitis, which progressed to chronic pancreatitis. This
phenotype reduces autophagy, increase apoptosis and necroptosis, inflammation and
fibrosis, as well as premature death of the animals. Knockout of Rip3 exacerbated
the apoptotic death of acinar cells, increased tissue damage, reduced macrophage
infiltration and further accelerated the death of the mice with Atg7-deficient
pancreas. The pancreatic degeneration induced by autophagy inhibition was
exacerbated by Rip3 deletion.
PMID- 28703809
TI - Epigallocatechin-3-gallate, a prototypic chemopreventative agent for protection
against cisplatin-based ototoxicity.
AB - Cisplatin-induced ototoxicity is one of the major factors limiting cisplatin
chemotherapy. Ototoxicity results from damage to outer hair cells (OHCs) and
other regions of the cochlea. At the cellular level, cisplatin increases reactive
oxygen species (ROS) leading to cochlear inflammation and apoptosis. Thus, ideal
otoprotective drugs should target oxidative stress and inflammatory mechanisms
without interfering with cisplatin's chemotherapeutic efficacy. In this study, we
show that epigallocatechin-3-gallate (EGCG) is a prototypic agent exhibiting
these properties of an effect otoprotective agent. Rats administered oral EGCG
demonstrate reduced cisplatin-induced hearing loss, reduced loss of OHCs in the
basal region of the cochlea and reduced oxidative stress and apoptotic markers.
EGCG also protected against the loss of ribbon synapses associated with inner
hair cells and Na+/K+ ATPase alpha1 in the stria vascularis and spiral ligament.
In vitro studies showed that EGCG reduced cisplatin-induced ROS generation and
ERK1/2 and signal transducer and activator of transcription-1 (STAT1) activity,
but preserved the activity of STAT3 and Bcl-xL. The increase in STAT3/STAT1 ratio
appears critical for mediating its otoprotection. EGCG did not alter cisplatin
induced apoptosis of human-derived cancer cells or cisplatin antitumor efficacy
in a xenograft tumor model in mice because of its inability to rescue the
downregulation of STAT3 in these cells. These data suggest that EGCG is an ideal
otoprotective agent for treating cisplatin-induced hearing loss without
compromising its antitumor efficacy.
PMID- 28703810
TI - MicroRNA-148a deficiency promotes hepatic lipid metabolism and
hepatocarcinogenesis in mice.
AB - miRNAs are involved in many physiologic and disease processes by virtue of
degrading specific mRNAs or inhibiting their translation. miR-148a has been
implicated in the control of tumor growth and cholesterol and triglyceride
homeostasis using in vitro or in vivo gene expression- and silencing-based
approaches. Here miR-148a knockout (KO) mice were used to investigate the
intrinsic role of miR-148a in liver physiology and hepatocarcinogenesis in mice.
miR-148a downregulation was found to be correlated with poor clinical outcomes in
hepatocellular carcinoma (HCC) patients. Under regular chow diet (RCD) or high
fat diet (HFD), miR-148a deletion significantly accelerated DEN-induced
hepatocarcinogenesis in mice. Mechanistically, miR-148a deletion promotes lipid
metabolic disorders in mice. Moreover, restoration of miR-148a reversed these
defects. Finally, miR-148a was found to directly inhibit several key regulators
of hepatocarcinogenesis and lipid metabolism. These findings reveal crucial roles
for miR-148a in the hepatic lipid metabolism and hepatocarcinogenesis. They
further identify miR-148a as a potential therapeutic target for certain liver
diseases, including cancer.
PMID- 28703812
TI - Electrosorption at functional interfaces: from molecular-level interactions to
electrochemical cell design.
AB - Adsorption at charged interfaces plays an important role across all aspects of
physical chemistry, from biological interactions within living organisms to
chemical processes such as catalysis and separations. With recent advances in
materials chemistry, there are a host of modified electrodes being investigated
for electrosorption, especially in separations science. In this perspective, we
provide an overview of functional interfaces being used for electrosorption,
ranging from electrochemical separations such as deionization and selective
product recovery to biological applications. We cover the various molecular
mechanisms which can be used to enhance ion capacity, and in some cases, provide
selectivity; as well as discuss the parasitic Faradaic reactions which often
impair electrosorption performance. Finally, we point to the importance of
electrochemical configurations, in particular the advantages of asymmetric cell
design, and highlight the opportunities for selective electrosorption brought
about by redox-mediated systems.
PMID- 28703811
TI - Cytoplasmic fragment of CD147 generated by regulated intramembrane proteolysis
contributes to HCC by promoting autophagy.
AB - Hepatocellular carcinoma (HCC) is one of the most lethal and prevalent cancers
worldwide. CD147 (EMMPRIN or basigin) is a leading gene relating to
hepatocarcinogenesis and metastasis, and is detected in transmembrane, exosome or
circulating forms in HCC patients. The endosome recycling of CD147 further
enhances the function of this oncoprotein from a dynamic perspective. However,
previous studies about CD147 mainly focused on one separate form, and little
attention has been paid to how the different forms of tumor-derived CD147
changes. Moreover, uncovering the roles of the residual C-terminal portion of
CD147 after shedding is inevitable to fully understand CD147 promoting tumor
progression. In this study, we discovered that under low-cholesterol condition,
CD147 endocytosis is inhibited but its shedding mediated by ADAM10 is enhanced.
Further procession of residual CD147 in the lysosome produces nuclear-localized
CD147-ICD (intracellular domain of CD147), which contributes to autophagy through
NF-kappaB-TRAIL-caspase8-ATG3 axis. As autophagy endows cancer cells with
increased adaptability to chemotherapy, and HAb 18 (a specific antibody targeting
CD147) inhibits CD147 shedding and sequential CD147-ICD enhances autophagy, we
found the combination of HAb 18 and cisplatin exhibited marked antitumor
efficiency.
PMID- 28703813
TI - The effects of transition-metal doping and chromophore anchoring on the
photocurrent response of titanium-oxo-clusters.
AB - Titanium-oxo-clusters (TOCs), [Ti6O4(OiPr)10(Cat)2(BA)2] (1) and
[Ti12M2O10(OEt)22(Cat)2(BA)4] (M = Co, Mn, Ni, 2-4; H2Cat = catechol, HBA =
benzoic acid) are prepared in one step in an in situ solvothermal synthesis.
Cluster structures of 2-4 can be considered as two 1 moieties merged together by
two transition metal atoms. Unlike most TOCs with sphere-like structures,
clusters 2-4 feature a unique single layered structure. They are not only
transition metal doped TOCs but also charge transfer (CT) TOCs, CT from Cat to
the TiO cluster core. Photoelectrodes were prepared by dipping the solution of
clusters on a porous TiO2 substrate. Photocurrent response properties of the
electrodes were studied in comparison with those of the electrodes of non-metal
doped 1 and the non-Cat coordinated Ti6 cluster. The results showed that the
photocurrent densities of metal doped clusters are higher than that of non-doped
clusters and the highest photocurrent density was found for the redox active
Co(ii) doped cluster. Charge transfer also plays an effective role in
photocurrent conversion under visible light irradiation.
PMID- 28703814
TI - Plasmon-induced absorption of blind chlorophylls in photosynthetic proteins
assembled on silver nanowires.
AB - We demonstrate that controlled assembly of eukaryotic photosystem I with its
associated light harvesting antenna complex (PSI-LHCI) on plasmonically active
silver nanowires (AgNWs) substantially improves the optical functionality of such
a novel biohybrid nanostructure. By comparing fluorescence intensities measured
for PSI-LHCI complex randomly oriented on AgNWs and the results obtained for the
PSI-LHCI/cytochrome c553 (cyt c553) bioconjugate with AgNWs we conclude that the
specific binding of photosynthetic complexes with defined uniform orientation
yields selective excitation of a pool of chlorophyll (Chl) molecules that are
otherwise almost non-absorbing. This is remarkable, as this study shows for the
first time that plasmonic excitations in metallic nanostructures can not only be
used to enhance native absorption of photosynthetic pigments, but also - by
employing cyt c553 as the conjugation cofactor - to activate the specific Chl
pools as the absorbing sites only when the uniform and well-defined orientation
of PSI-LHCI with respect to plasmonic nanostructures is achieved. As absorption
of PSI alone is comparatively low, our approach lends itself as an innovative
approach to outperform the reported-to-date biohybrid devices with respect to
solar energy conversion.
PMID- 28703815
TI - From dynamic self-assembly to networked chemical systems.
AB - Although dynamic self-assembly, DySA, is a relatively new area of research, the
past decade has brought numerous demonstrations of how various types of
components - on scales from (macro)molecular to macroscopic - can be arranged
into ordered structures thriving in non-equilibrium, steady states. At the same
time, none of these dynamic assemblies has so far proven practically relevant,
prompting questions about the field's prospects and ultimate objectives. The main
thesis of this Review is that formation of dynamic assemblies cannot be an end in
itself - instead, we should think more ambitiously of using such assemblies as
control elements (reconfigurable catalysts, nanomachines, etc.) of larger,
networked systems directing sequences of chemical reactions or assembly tasks.
Such networked systems would be inspired by biology but intended to operate in
environments and conditions incompatible with living matter (e.g., in organic
solvents, elevated temperatures, etc.). To realize this vision, we need to start
considering not only the interactions mediating dynamic self-assembly of
individual components, but also how components of different types could coexist
and communicate within larger, multicomponent ensembles. Along these lines, the
review starts with the discussion of the conceptual foundations of self-assembly
in equilibrium and non-equilibrium regimes. It discusses key examples of
interactions and phenomena that can provide the basis for various DySA modalities
(e.g., those driven by light, magnetic fields, flows, etc.). It then focuses on
the recent examples where organization of components in steady states is coupled
to other processes taking place in the system (catalysis, formation of dynamic
supramolecular materials, control of chirality, etc.). With these examples of
functional DySA, we then look forward and consider conditions that must be
fulfilled to allow components of multiple types to coexist, function, and
communicate with one another within the networked DySA systems of the future. As
the closing examples show, such systems are already appearing heralding new
opportunities - and, to be sure, new challenges - for DySA research.
PMID- 28703816
TI - Effect of low-purity Fenton reagents on toxicity of textile dyeing effluent to
Daphnia magna.
AB - This study aimed to identify the source of toxicity in textile dyeing effluent
collected from February to July 2016, using Daphnia magna as a test organism.
Toxicity identification evaluation (TIE) procedures were used to identify the
toxicants in textile dyeing effluent, and Jar testing to simulate the Fenton
process was conducted to identify the source of toxicants. Textile dyeing
effluent was acutely toxic to D. magna [from 1.5 to 9.7 toxic units (TU)] during
the study period. TIE results showed that Zn derived from the Fenton process was
a key toxicant in textile dyeing effluent. Additionally, Jar testing revealed
that low-purity Fenton reagents (FeCl2 and FeSO4), which contained large amounts
of Zn (89 838 and 610 mg L-1, respectively), were the source of toxicity.
Although we were unable to conclusively identify the residual toxicity (approx.
1.4 TU of 9.71 TU) attributable to unknown toxicants in textile dyeing effluent,
the findings of this study suggest that careful operation of the Fenton treatment
process could contribute to eliminating its unintended toxic effects on aquatic
organisms.
PMID- 28703817
TI - Dissipative out-of-equilibrium assembly of man-made supramolecular materials.
AB - The use of dissipative self-assembly driven by chemical reaction networks for the
creation of unique structures is gaining in popularity. In dissipative self
assembly, precursors are converted into self-assembling building blocks by the
conversion of a source of energy, typically a photon or a fuel molecule. The self
assembling building block is intrinsically unstable and spontaneously reverts to
its original precursor, thus giving the building block a limited lifetime. As a
result, its presence is kinetically controlled, which gives the associated
supramolecular material unique properties. For instance, formation and properties
of these materials can be controlled over space and time by the kinetics of the
coupled reaction network, they are autonomously self-healing and they are highly
adaptive to small changes in their environment. By means of an example of a
biological dissipative self-assembled material, the unique concepts at the basis
of these supramolecular materials will be discussed. We then review recent
efforts towards man-made dissipative assembly of structures and how their unique
material properties have been characterized. In order to help further the field,
we close with loosely defined design rules that are at the basis of the discussed
examples.
PMID- 28703818
TI - Evaporation-condensation effects on the thermoelectric performance of PbTe-based
couples.
AB - In thermoelectric (TE) generators, Carnot efficiency maximization, by increasing
the hot side temperature, is required for maximizing the heat to electricity
energy conversion. Yet, volatile species sublimation, apparent in many TE
material classes including tellurides, selenides, sulfides, silicides and more,
limits the hot side temperature to a certain level, depending on the specific
composition. In the current research, the TE performance of a PbTe-based couple
subjected to a large temperature difference of an extreme hot side temperature of
600 degrees C and cold side temperature of 60 degrees C for 456 h was
investigated both experimentally and theoretically and was correlated to
evaporation-condensation effects in the vicinity of the hot-side temperature.
Only moderate degradation of the maximal electrical power and efficiency was
observed showing the promising potential of employing of such couples in
practical TE applications.
PMID- 28703819
TI - Decorating graphene with size-selected few-atom clusters: a novel approach to
investigate graphene-adparticle interactions.
AB - We investigated the interaction between size-selected Au2 and Au3 clusters and
graphene. Hereto preformed clusters are deposited on graphene field-effect
transistors, a novel approach which offers a high control over the number of
atoms per cluster, the deposition energy and the deposited density. The induced p
doping and charge carrier scattering indicate that a major part of the deposited
clusters remains on the graphene flake as either individual or sub-nm coalesced
entities. This is independently confirmed by scanning electron microscopy on the
same devices after current annealing. Our novel approach provides perspectives
for the electronic sensing of metallic clusters down to their atom-by-atom size
specific properties, and exploiting the tunability of clusters for tailoring
desired properties in graphene.
PMID- 28703820
TI - Liquid like nucleation in free-standing nanoscale films.
AB - The concept of a critical nucleus size (r*) is of pivotal importance in phase
transformations involving nucleation and growth. The current investigation
pertains to crystallization in nanoscale thin films and study of the same using
high resolution lattice fringe imaging (HRLFI) and finite element simulations.
Using the CuZrAl bulk metallic glass system as a model system for this study, we
demonstrate a liquid like nucleation behaviour in nanoscale free-standing films
upon heating. The r* for the formation of the Cu10Zr7 phase in thin films (of
decreasing thickness) approaches that of the r* for the formation of the crystal
from a liquid (i.e.). Working in the nucleation dominant regime, we introduce the
concept of 'depth sensitive lattice fringe imaging'. The thickness of the film is
determined by electron energy loss spectroscopy and the strain energy of the
system is computed using finite element computations.
PMID- 28703821
TI - On the metastability of doubly charged homonuclear diatomics.
AB - Generalized valence bond (GVB) and spin-coupled (SC) calculations were used in
conjunction with the generalized product function energy partitioning (GPF-EP)
method to describe the origin of metastability in doubly charged homonuclear
dications. A model to describe the formation of metastable potential wells based
on interference and quasi-classical effects is presented. The GPF-EP picture of
dications is the result of polarization-aided strong covalent bonding surpassing
Coulomb electrostatic repulsion. Important differences in the quasi-classical
density profiles of He22+ and Ne22+ reveal the underlying mechanism that could
lead to bound or unbound states. Finally, the nature of the chemical bond of
N22+, O22+, and F22+ is described. The results suggest that the ground states of
the mentioned dications are bounded and that the depth of the potential wells of
these exotic species is related to the interference effect, in the same way as in
previously studied neutral molecules.
PMID- 28703823
TI - Kinetics study of the CN + CH4 hydrogen abstraction reaction based on a new ab
initio analytical full-dimensional potential energy surface.
AB - We have developed an analytical full-dimensional potential energy surface, named
PES-2017, for the gas-phase hydrogen abstraction reaction between the cyano
radical and methane. This surface is fitted using high-level ab initio
information as input. Using the PES-2017 surface, a kinetics study was performed
via two theoretical approaches: variational transition-state theory with
multidimensional tunnelling (VTST-MT) and ring polymer molecular dynamics (RPMD).
The results are compared with the experimental data. In the whole temperature
range analysed, 300-1500 K, both theories agree within a factor of <2,
reproducing the experimental behaviour taking into account the experimental
uncertainties. At high temperatures, where the recrossing effects dominate and
the RPMD theory is exact, both theories differ by a factor of about 20%; while at
low temperatures this difference is larger, 45%. Note that in this temperature
regime, the tunnelling effect is negligible. The CN + CH4/CD4 kinetic isotope
effects are important, reproducing the scarce experimental evidence. The good
agreement with the ab initio information used in the fitting process (self
consistency test) and with the kinetic behaviour in a wide temperature range
gives confidence and strength to the new surface.
PMID- 28703822
TI - Spatiotemporal presentation of exogenous SDF-1 with PLGA nanoparticles modulates
SDF-1/CXCR4 signaling axis in the rodent cortex.
AB - Stromal cell-derived factor-1 (SDF-1) and its key receptor CXCR4 have been
implicated in directing cellular recruitment for several pathological/disease
conditions thus also gained considerable attention for regenerative medicine. One
regenerative approach includes sustained release of SDF-1 to stimulate prolonged
stem cell recruitment. However, the impact of SDF-1 sustained release on the
endogenous SDF-1/CXCR4 signaling axis is largely unknown as auto-regulatory
mechanisms typically dictate cytokine/receptor signaling. We hypothesize that
spatiotemporal presentation of exogenous SDF-1 is a key factor in achieving long
term manipulation of endogenous SDF-1/CXCR4 signaling. Here in the present study,
we sought to probe our hypothesis using a transgenic mouse model to contrast the
spatial activation of endogenous SDF-1 and CXCR4 in response to exogenous SDF-1
injected in bolus or controlled release (PLGA nanoparticles) form in the adult
rodent cortex. Our data suggests that the manner of SDF-1 presentation
significantly affected initial CXCR4 cellular activation/recruitment despite
having similar protein payloads over the first 24 h (~30 ng for both bolus and
sustained release groups). Yet, one week post-injection, this response was
negligible. Therefore, the transient nature CXCR4 recruitment/activation in
response to bolus or controlled release SDF-1 indicated that cytokine/receptor
auto-regulatory mechanisms may demand more complex release profiles (i.e. delayed
and/or pulsed release) to achieve sustained cellular response.
PMID- 28703824
TI - Chromatographic and mass spectrometry analysis of wheat flour prolamins, the
causative compounds of celiac disease.
AB - Immunogenic gluten peptides trigger Celiac Disease (CD), an adaptive immune
response in genetically predisposed individuals. Given the structural similarity
between all gluten proteins their individual CD influence is not clear. Hence,
the extraction, separation and characterization of wheat gluten proteins have
become relevant to measure their individual potential immunoreactivity. Wheat
proteins were extracted from commercial wheat flour and further isolated by
preparative HPLC. The resulting richest gliadin sub-fractions were characterized
by nano-LC-MS/MS following a shotgun proteomic approach in order to identify the
prolamins in the original commercial wheat flour. It was found that the gliadin
extract was additionally composed of glutenins and avenin-like proteins. Accurate
prolamin identification has emerged as a need to delve deep into the influence of
each fraction on the onset of celiac disease. After protein characterization, the
immunoreactivity towards the main epitope related to CD was verified by ELISA and
western blotting for several different gluten fractions.
PMID- 28703825
TI - Evaluation of DFO-HOPO as an octadentate chelator for zirconium-89.
AB - The future of 89Zr-based immuno-PET is reliant upon the development of new
chelators with improved stability compared to the currently used deferoxamine
(DFO). Herein, we report the evaluation of the octadentate molecule DFO-HOPO (3)
as a suitable chelator for 89Zr and a more stable alternative to DFO. The
molecule showed good potential for the future development of a DFO-HOPO-based
bifunctional chelator (BFC) for the radiolabelling of biomolecules with 89Zr.
This work broadens the selection of available chelators for 89Zr in search of
improved successors to DFO for clinical 89Zr-immuno-PET.
PMID- 28703826
TI - Synthesis of carbonylated heteroaromatic compounds via visible-light-driven
intramolecular decarboxylative cyclization of o-alkynylated carboxylic acids.
AB - An efficient strategy for the easy access to carbonylated heteroaromatic
compounds has been developed via a visible-light-promoted intramolecular
decarboxylative cyclization reaction of o-alkynylated carboxylic acids. This
method is characterized by its benign conditions and the tolerance to a wide
range of functionalities.
PMID- 28703827
TI - Palladium(ii) in liquid ammonia: an investigation of structural and dynamical
properties by applying quantum mechanical charge field molecular dynamics (QMCF
MD).
AB - The structural and dynamical properties of Pd2+ in liquid ammonia have been
investigated via quantum mechanical charge field molecular dynamics. Similar to
the case of aqueous Pd2+, a six-fold coordination polyhedron in the form of a
tetrahedrally elongated octahedron is observed with two ligands in axial
positions forming an extended first shell. To highlight the difference in
solvation between the aqueous and ammonia case a selection based on the angular
radial distribution with respect to the well-known square planar motif was
applied also providing a detailed understanding of ligand exchange between the
extended first and second shells. All structural properties resulting from this
investigation compare well with the available solid-state data of various N
containing complexes. From the dynamical perspective, Pd2+ in liquid ammonia
forms a more flexible complex with a higher rate of ligand exchange than that of
its aqueous counterpart.
PMID- 28703828
TI - Quantifying reaction kinetics of the non-enzymatic decarboxylation of pyruvate
and production of peroxymonocarbonate with hyperpolarized 13C-NMR.
AB - The transient nature of intermediate states in chemical reactions has made their
detailed investigation difficult. In this study, we demonstrate the utility of
hyperpolarized 13C-NMR to directly observe and quantify the kinetics of the
intermediate compound in the non-enzymatic decarboxylation of pyruvate via H2O2
with time resolutions of <1 s. Reactants were sequentially added to a reaction
vessel within a 9.4 T NMR magnet while continuously acquiring spectra with a low
flip angle, producing the first direct observation at room temperature of the
previously proposed reaction intermediate, 2-hydroperoxy-2-hydroxypropanoate. We
also performed a series of NMR experiments to determine the identity of a
previously unidentified peak, which was found to be peroxymonocarbonate, the
product of the side reaction between HCO3-/CO2 and H2O2/OOH-. Using the
information obtained from these experiments, we developed a kinetic model which
fully describes the mechanism of reaction and can be fit to experimental data to
simultaneously determine multiple kinetic rate constants over several orders of
magnitude. We also discuss the application of this reaction to the production of
hyperpolarized bicarbonate for pH imaging experiments. This study presents a
template for the use of hyperpolarized 13C-NMR to study the kinetics and reaction
mechanisms of innumerable organic reactions which involve polarizable substrates.
PMID- 28703829
TI - Enhancement of the solubility and antioxidant capacity of alpha-linolenic acid
using an oil in water microemulsion.
AB - The applications of alpha-linolenic acid (ALA) in the food industry are
restricted due to its poor water solubility and antioxidant stability. This study
concentrates on developing an ALA-loaded microemulsion (ALA-ME) to enhance its
solubility and antioxidant capacity. The formulation of the microemulsion was
investigated based on pseudoternary phase diagrams. The ALA-ME was characterized
by using electrical conductivity, viscosity and transmission electron microscopy
(TEM). The microstructure of the ALA-ME was probed using nuclear magnetic
resonance (1H-NMR). The results proved that ALA-ME consisted of spheroidal
droplets with 20-40 nm diameter. A structural transformation from water in oil
(W/O) to oil in water (O/W) occurred, as seen from the electrical conductivity
determination. The 1H-NMR results revealed a transition of the ALA position
encapsulated from the core area of the microemulsion to the lipophilic layer of
the surfactant. Furthermore, two microstructural models of ALA-ME were proposed.
The antioxidant evaluation demonstrated that the ALA antioxidant capacity in
microemulsions was enhanced to about 80% compared with that of ALA in oil
solution.
PMID- 28703830
TI - Rapid real-time recirculating PCR using localized surface plasmon resonance
(LSPR) and piezo-electric pumping.
AB - Rapid detection and characterization of pathogens in patients with bloodstream
infections (BSIs) is a persistent problem for modern medicine, as current
techniques are slow or provide incomplete diagnostic information. Real-time
polymerase chain reaction (qPCR) allows specific detection of a wide range of
targets and quantification of pathogenic burdens to aid in treatment planning.
However, new technological advances are required for a rapid and multiplex
implementation of qPCR in clinical applications. In this paper, the feasibility
of a novel microfluidic platform for qPCR is presented, integrating highly
sensitive, label-free localized surface plasmon resonance (LSPR) imaging of DNA
hybridization into a recirculating chip design for real-time analysis. Single
target and multiplex detection of DNA target amplification are demonstrated, with
a limit of detection of 5 fg MUL-1 of E. coli DNA for single target PCR,
correlating with approximately 300 bacteria per mL. The results of this study
demonstrate the potential of this platform for simultaneous real-time detection
of multiple target genes within 15 minutes that could provide live saving
benefits in patients with BSIs.
PMID- 28703831
TI - Energetics and the molecular structure of an ion-paired supramolecular system in
water.
AB - The forces that bind the components of a host-guest complex to generate a stable
supramolecular system are noncovalent interactions. The enthalpy of this
association, DeltaasH degrees , usually measured using calorimetry, quantifies
the magnitude of such interactions and is directly related to the stability of
the supramolecular complex formed. Using Calvet calorimetry to determine the
enthalpies of solution and reaction in water, the enthalpy of association was
derived for a supramolecular system formed by the anionic macrocycle anti
disulfodibenzo[24]crown-8 ([DSDB24C8]2-) and the dicationic guest paraquat
[PQT]2+. The calorimetric results show an exothermic association process, which
indicates the generation of strong interactions between the components of the ion
pair. This is consistent with the formation of a stable supramolecular complex
[PQT][DSDB24C8], whose spatial arrangement in aqueous solution is proposed based
on spectroscopic analysis.
PMID- 28703832
TI - Protective vascular effects of quercitrin in acute TNBS-colitis in rats: the role
of nitric oxide.
AB - Quercitrin (quercetin 3-rhamnoside) is a bioflavonoid with anti-inflammatory
activity in experimental colitis. Several studies have suggested that vascular
injury might be a primary process in Crohn's disease, but there is no information
about the function of the mesenteric bed in the experimental models of colitis.
The aims of this study were to analyse whether the reactivity to vasoconstrictor
agents is altered in the mesenteric vascular bed from animals with colitis
induced by administration of trinitrobenzenesulfonic acid (TNBS) in the early
stages of this pathology, and to determine the effects of quercitrin on such
vascular alterations. Contraction of mesenteric beds produced by vasoconstrictor
agents such as noradrenaline and KCl is reduced in rats in the early stages of
experimental TNBS-induced colitis. This alteration was partially reverted by non
selective nitric oxide synthase (NOS) inhibition with N-nitro-l-arginine
methylester, and enhanced by non-selective cyclooxygenase (COX) inhibition with
indomethacin. However, the endothelium-dependent relaxant responses to
acetylcholine were not significantly altered. iNOS, COX-2, NOX-1, tumor necrosis
factor alpha (TNFalpha) and interleukin 1beta (IL1beta) expressions were higher
in the mesenteric arteries from TNBS-treated rats, without changes in both eNOS
expression and eNOS-Ser1177 phosphorylation. The in vivo pre-treatment with 5 mg
kg-1 of the flavonoid quercitrin reverts both the early hyporesponse of
mesenteric arteries to noradrenaline and the up-regulation of iNOS, COX2, NOX1,
TNFalpha and IL1beta in colitic rats. In conclusion, quercitrin improves the
impaired mesenteric vascular reactivity in the acute phase of this colitis model,
at least in part by reducing NO overproduction from iNOS.
PMID- 28703833
TI - Nanoparticle cellular uptake by dendritic wedge peptides: achieving single
peptide facilitated delivery.
AB - Significant efforts are being undertaken to optimize the cargo carrying capacity
and especially the cellular delivery efficiency of functionalized nanoparticles
for applications in biological research and pharmacological delivery. One
approach to increasing nanoparticle surface cargo display capacity is to decrease
the number of moieties required for mediating cellular delivery by improving
their efficiency. We describe a series of multivalent cell penetrating peptide
(CPP) dendrimers that facilitate rapid cellular delivery of prototypical
nanoparticle-semiconductor quantum dots (QDs). The modular CPP dendrimers were
assembled through an innovative convergent oxime ligation strategy between
(Arg9)n motifs and a dendritic QD-coordination scaffold. Dendrimeric peptides
sequentially incorporate a terminal (His)6 motif for metal-affinity QD
coordination, a Pro9 spacer, a branching poly-lysine scaffold, and wedged display
of (Arg9)n binding motifs with n = 1*, 2*, 4*, 8*, 16* multivalency. QD dendrimer
display capacity was estimated using structural simulations and QD-(Arg9)1-16
conjugates characterized by dynamic light scattering along with surface plasmon
resonance-based binding assays to heparan sulfate proteoglycan surfaces. Cellular
uptake via endocytosis was confirmed and peptide delivery kinetics investigated
as a function of QD-(Arg9)1-16 conjugate exposure time and QD assembly ratio
where cellular viability assays reflected no overt cytotoxicity. The ability of
single dendrimer conjugates to facilitate cellular uptake was confirmed for QD
(Arg9)2-16 repeats along with the ability to deliver >850 kDa of protein cargo
per QD. Minimizing the number of CPPs required for cellular uptake is critical
for expanding nanoparticle cargo carrying capacity and can allow for inclusion of
additional sensors, therapeutics and contrast agents on their surface.
PMID- 28703834
TI - Fabrication of nanoporous graphene/polymer composite membranes.
AB - Graphene is currently investigated as a promising membrane material in which
selective pores can be created depending on the requirements of the application.
However, to handle large-area nanoporous graphene a stable support material is
needed. Here, we report on composite membranes consisting of large-area single
layer nanoporous graphene supported by a porous polymer. The fabrication is based
on ion-track nanotechnology with swift heavy ions directly creating atomic pores
in the graphene lattice and damaged tracks in the polymer support. Subsequent
chemical etching converts the latent ion tracks in the supporting polymer foil,
here polyethylene terephthalate (PET), into open microchannels while the
perfectly aligned pores in the graphene top layer remain unaffected. To avoid
unintentional damage creation and delamination of the graphene layer from the
substrate, the graphene is encapsulated by a protecting poly(methyl methacrylate)
(PMMA) layer. By this procedure a stable composite membrane is obtained
consisting of nanoporous graphene (coverage close to 100%) suspended across
selfaligned track-etched microchannels in a polymer support film. Our method
presents a facile way to create high quality suspended graphene of tunable pore
size supported on a flexible porous polymeric support, thus enabling the
development of membranes for fast and selective ultrafiltration separation
processes.
PMID- 28703835
TI - Assembling phosphorene flexagons for 2D electron-density-guided nanopatterning
and nanofabrication.
AB - To build upon the rich structural diversity in the ever-increasing polymorphic
phases of two-dimensional phosphorene, we propose different assembly methods
(namely, the "bottom-up" and "top-down" approaches) that involve four commonly
reported parent phases (i.e. the alpha-, beta-, gamma-, and delta-phosphorene) in
combination with the lately reported remarkably low-energy one-dimensional
defects in alpha-phosphorene. In doing so, we generate various periodically
repeated phosphorene patterns in these so-called phosphorene flexagons and
present their local electron density (via simulated scanning tunneling microscopy
(STM) images). These interesting electron density patterns seen in the flexagons
(mimicking symmetry patterns that one may typically see in a kaleidoscope) may
assist as potential 2D templates where electron-density-guided nanopatterning and
nanofabrication in complex organized nanoarchitectures are important.
PMID- 28703836
TI - Monolithic zirconia and digital impression: case report.
AB - AIMS: The aim of this study is to present a clinical case of a full arch
prosthetic rehabilitation on natural teeth, combining both digital work-flow and
monolithic zirconia. PATIENTS AND METHODS: Digital impression was taken with an
intraoral optical scanner (CS3500, Carestream Dental, Atlanta, GA, USA). A
prosthetic rehabilitation was realized on natural teeth using monolithic zirconia
from 1.6 to 1.4 and from 2.7 to 2.4 frameworks, while in the aesthetic area (from
2.3 to 1.3), technicians left on the structure a 0.8 mm vestibular space for
ceramic layering. DISCUSSION: The combination of digital impression technology
and the use of the monolithic zirconia had demonstrated the delivery of the final
prosthetic device in a quick time without the need to remodel functional or
aesthetic areas. The digital work-flow combines intraoral optical impression
techniques and CAD/CAM technology, in order to achieve a fully digital and
successful way to deliver prosthetic restorations to patients, providing
aesthetics and function in shorter intervals of time. The clinical outcome of
this study was satisfactory but a long-term evaluation is needed.
PMID- 28703837
TI - Multiple stab wounds: understanding the manner of death through the psychological
autopsy.
AB - A 48-year-old physical therapist with no history of psychiatric disorders or
suicidal tendencies was found dead by his relatives inside his apartment.
Multiple stab wounds were present on the chest and the abdomen. Several more
superficial cuts were also seen on the neck and the left wrist. At the death
scene, there was a large pool of blood in the room, with secondary droplets and
stains; a kitchen knife was found beside the body, and a suicide note on a table.
Especially the number of wounds raised strong suspicion of a homicide in the
first instance but some circumstances (the farewell letter, the absence of
clothing injuries, no signs of third-party involvement) and autopsy findings
(absence of defense or blunt injuries, the localization of the wounds, the
presence of hesitation marks) pointed toward a suicide etiology. Because of the
many stab injuries and the lack of a psychiatric history, further forensic
investigations were required including a so-called psychological autopsy. This
case report highlights that only a comprehensive interpretation of all the
elements (circumstances, the scene of death, autopsy findings, and psychological
autopsy) can lead to the correct solution of atypical cases of suicide.
PMID- 28703838
TI - Can trans resveratrol plus d-chiro-inositol and myo-inositol improve maternal
metabolic profile in overweight pregnant patients?
AB - OBJECTIVE: To investigate the effect of trans-resveratrol from Polygonum
cuspidatum/magnesium hydroxide complex, trademark Revifast(r), plus D-chiro
inositol (DCI) and Myo-inositol (MI) during spontaneous pregnancies in overweight
patients in a pilot study. STUDY DESIGN: A one-year, prospective, randomized,
double-blinded, placebo-controlled single center clinical study was carried out
on overweight pregnant women. 110 patients were randomized in 3 groups to
receive: Revifast(r) with DCI/MI (group I), DCI/MI alone (group II) or control
group (group III) for 30 and 60 days. The main outcomes were to explore the lipid
profile (total cholesterol, LDL, HDL, TG) and glucose levels, after 30 and 60
days of therapy. RESULTS: No difference in systolic and diastolic parameters
among 3 groups during study. All blood chemistry parameters improved compared to
placebo at 30 days already, but significantly to 60 days, respect placebo. By
comparing the two treatment groups, group I demonstrates significantly improved
lipid and glucose parameters than group II, which are at 30 to 60 days of
treatment. CONCLUSIONS: The supplementation of Trans-resveratrol, Revifast(r) in
addition to DCI/MI in overweight pregnant woman with an elevated fasting glucose
improves glucose levels, Total Cholesterol, LDL and TG.
PMID- 28703839
TI - 2014-2017. How medically assisted reproduction changed in Italy. A short
comparative synthesis with European countries.
AB - More than ten years after law n. 40 of February 19, 2004 became effective,
regulation on medically assisted reproduction has dramatically changed outlook.
The authors report on the steps that led to these changes through Courts'
rulings, the Supreme Court's verdicts and the European Court of Human Rights'
decisions, as well as ministerial regulations and guidelines concerning medically
assisted reproduction. The aforementioned jurisprudential evolution was set to
reach a new balance between the embryo's right to its own dignity and the woman's
right to health and freedom of self-determination in reproduction. No court
ruling denies that embryos have also to be safeguarded. In fact, there are still
numerous prohibitions, including using embryos for experimental purposes. Judges
aim primarily at avoiding that embryos' rights overcome the right to parenthood.
The authors review the legislation of the various European countries: some have
adopted a legislation to regulate medically assisted reproduction, while others
have developed in this field some recommendations or guidelines. This is why they
call for enactment of a European law governing the implementation/operational
methods of medically assisted reproduction in order to avoid the scourge of
procreative tourism to countries that have a more permissive law.
PMID- 28703840
TI - Medication-related osteonecrosis of the jaws (MRONJ) and quality of life
evaluation: a pilot study.
AB - BACKGROUND: MRONJ (medication related osteonecrosis of the jaws) is a well-known
side effect of certain drugs, which are used to influence bone metabolism for the
cure of osteo-metabolic or cancer diseases. The aim of this study is to assess
the quality of life (QOL) under a physical and mental point of view in patients
affected by MRONJ compared with the general population. METHODS: The study has
been accomplished through the administration of the SF-12 questionnaire: 30
patients of the MRONJ group were evaluated. RESULTS: Significant differences
based on the level of education and age of the subjects, on the location and
finally on the stage of necrosis of the jaw have been identified. In this pilot
study the test sample shows how MRONJ can aggravate the conditions of patients,
above all under a physical point of view. CONCLUSIONS: Prevention of MRONJ and
its symptoms as dysphagia, oral pain, immunological compromission and the need of
frequent antibiotic therapies is a crucial part of modern oral pathology and
dentistry, above all for oncologic patients who already have a general decrease
of physical and mental activities, leading to a poor quality of life.
PMID- 28703841
TI - Reliability of adapted version of Italian Label tobacco Impact Index for the
adolescent: ALII.
AB - OBJECTIVE: The aim of this study is to assess the reliability of the Adolescent
Label Impact Index (ALII) , it is an adolescent adapted version of Italian LII of
the tobacco products warnings. MATERIAL AND METHODS: A sample including students
aged 13-15 years was considered. The ALII is constructed by 4 items: salience,
harm, quitting and forgo. The questionnaire was self-administered to study
participants twice with 3 days between each administration (T1 and T2) to measure
reliability. The internal consistency using Cronbach's alpha and Corrected Item
Total Correlations (CITC) and the test-retest reliability applying Pearson's
correlation were computed. RESULTS: Cronbach's alpha ranges from 0.625 at T1 to
0.715 at T2. The "salience" resulted the item with the lowest CITC value
(=0.281). The Pearson's coefficient was r=0.909 (p<0.001). CONCLUSIONS: The
instruments is low in cost and easy to administer and analyses in a setting
people aged 13-15 years. The ALII shown an acceptable consistency and excellent
stability over time. However, attention has to be paid when the ALII is
administered to the no smoking teens and who has never seen the tobacco product
labels to allow an appropriate interpretation of the data collected.
PMID- 28703842
TI - The neutrophil-lymphocyte ratio in children with atopic dermatitis: a case
control study.
AB - BACKGROUND: Neutrophil-lymphocyte ratio(NLR) is a novel marker for the evaluation
of inflammation and has not been evaluated previously in patients with AD.
OBJECTIVE: To investigate the relationship between NLR and the clinical findings
of AD. METHODS: Sixty-six children with AD were included in the study.The control
group was included 66 children who have no allergic and chronic diseases.The
immunoglobulin(Ig)E levels and complete blood count were measured. Skin prick
tests were performed using the same antigens for all patients. RESULTS: NLR was
not significant between the patient and control groups (p>0.05).The patients with
AD were divided into 3 groups according to their SCORAD score as mild, moderate
and severe AD.No statistically significant difference was present between groups
in terms of demographic and clinical characteristics,eosinohil-lymphocyte
ratio,eosinophil-neutrophil ratio,the percentage of eosinophil, IgE,the
sensitivity of skin tests(p>0.05). However,NLR and sensitivity to house dust mite
were significantly different among groups(respectively,p=0.037,p:0.043).SCORAD
scores were weak positively correlated with NLR levels,eosinophil-lymphocyte
ratio and the sensitivity of house dust mite
(respectively,r:0.329;p:0.007,r:0.264;p:00035,r:0.325;p:0.008). CONCLUSIONS: We
didn't found significant difference in term of mean NLR betweeen patients with AD
and control group. NLR was found significantly higher in severe AD patients than
mild AD patients.The house dust mite sensitivity, eosinohil-lymphocyte ratio and
NLR were correlated with AD severity.
PMID- 28703843
TI - Infections in hospital departments. What is Hospital Responsibility?
AB - Infections in hospitals still have a high incidence and many of them could be
avoided through better welfare standards. To try to overcome them, a strategy
based on prevention is needed, but cleaning, disinfection and sterilization
procedures are also a key tool. It is important to provide for all healthcare
professionals a constant update and the creation of protocols that take into
account the technical, scientific and economic aspects, but also specific
operational needs, so that the proposed solutions can be applied in daily
routines. The authors outline the mandatory duties to the doctors and hospital
and underline the need to document in the clinical record the treatments
performed. In case of infections occurred in hospital environment, the patient
must demonstrate the guilty nature of the hospital's conduct, the existence of a
harm and the causal connection. The hospital must demonstrate that asepsis
measures were adopted according to the actual scientific knowledge and they must
cover not only the treatment but also the diagnosis, all the activities prior to
surgery and the postoperative phase. The sentences examined show that hospitals
can avoid being accused of negligence and imprudence only if they can prove that
they have implemented all prophylaxis measures contained in the guidelines and
protocols. They must demonstrate that the infection was caused by an
unforeseeable event. While some initiatives to improve the quality of hospital
care have already allowed a decrease in the incidence and cost of these
infections, much remains to be done.
PMID- 28703844
TI - [Risk factors' analysis of transient and permanent hypoparathyroidism after
thyroidectomy].
AB - AIMS: This review evaluates those main risk factors that can affect patients
undergoing thyroidectomy, to reach a better pre- and post-operative management of
transient and permanent hypoparathyroidism. DISCUSSION: The transient
hypoparathyroidism is a potentially severe complication of thyroidectomy,
including a wide range of signs and symptoms that persists for a few weeks. The
definitive hypoparathyroidism occurs when a medical treatment is necessary over
12 months. Risk factors that may influence the onset of this condition after
thyroidectomy include: pre- and post-operative biochemical factors, such as serum
calcium levels, vitamin D blood concentrations and intact PTH. Other involved
factors could be summarized as follow: female sex, Graves' or thyroid neoplastic
diseases, surgeon's dexterity and surgical technique. The medical treatment
includes the administration of calcium, vitamin D and magnesium sometimes.
CONCLUSIONS: Although biological and biochemical factors could be related to
iatrogenic hypoparathyroidism, the surgeon's experience and the used surgical
technique still maintain a crucial role in the aetiology of this important
complication.
PMID- 28703845
TI - The value of dual-source multidetector-row computed tomography in determining
pulmonary blood supply in patients with pulmonary atresia with ventricular septal
defect.
AB - BACKGROUND: Primary evaluation of patients with pulmonary atresia with
ventricular septal defect (PA-VSD) traditionally relies upon echocardiography and
conventional cardiac angiography (CCA). Cardiac angiography is considered the
gold standard for delineation of anatomy in children with PA-VSD. Data comparing
CCA and dual-source multidetector-row computed tomography angiography (MDCT) in
PA-VSD patients is limited. The objective of this study was to test the
hypothesis that MDCT is equivalent to CCA for anatomic delineation in these
patients. MATERIALS AND METHODS: Twenty-eight patients with PA-VSD underwent CCA
and MDCT in close proximity to each other without interval therapy. A
retrospective review of these 28 patients was performed. All MDCT data of
pulmonary artery morphology, major aortopulmonary collateral arteries (MAPCAs)
and type of blood supply (dual vs. single supply) were evaluated by blinded
experts and results were compared with CCA. RESULTS: Twenty-eight patients had
adequate size right and left pulmonary arteries (21 confluent and 7 non
confluent). Seven patients had complete absence of native pulmonary artery and 3
patients had stenosis of distal branches of pulmonary arteries; all had MAPCAs
from descending thoracic aorta and/or subclavian arteries. Sensitivity,
specificity, positive and negative predictive value of MDCT for detecting
confluent of pulmonary arteries, absence of native pulmonary artery and stenosis
of pulmonary arteries were all 100%. Moreover, accuracy of detecting MAPCAs was
excellent. CONCLUSIONS: These results suggest that MDCT and CCA are equivalent in
their ability to delineate pulmonary artery anatomy and MAPCAs. Dual source MDCT
provides high diagnostic accuracy in evaluation of pulmonary blood supply in
patients with PA-VSD and allows precise characterisation of the condition of
pulmonary arteries and MAPCAs which is of paramount importance in managing
patients with PA-VSD. (Folia Morphol 2018; 77, 1: 116-122).
PMID- 28703846
TI - Protective effect of garlic extract against maternal and foetal cerebellar damage
induced by lead administration during pregnancy in rats.
AB - BACKGROUND: In spite of its industrial usefulness and varied daily uses, lead
(Pb) pollution is a widespread ecological problem that faces the humans in the
21th century. Pb was found to produces a wide range of toxic effects including
neurotoxicity especially to the developing and young offspring. Recently, the
utilisation of herbal plants has received a significant attention where there has
been rising awareness in their therapeutic use; among these is the garlic. In
light of the above, the current study is designed experimentally in female
pregnant rats in order to investigate the beneficial role of garlic extract in
the protection from the maternal and foetal cerebellar damage produced by
administration of different doses of Pb during pregnancy. MATERIALS AND METHODS:
Positively pregnant female rats were divided into five groups; one control group,
two Pb-treated groups (exposed to 160 and 320 mg/kg b.w. of Pb, respectively) and
two groups treated with both Pb and garlic (exposed to Pb as previous groups
together with 250 mg/kg b.w./day of garlic extract). Treatments started from day
1 to day 20 of pregnancy, where the mother rats of different experimental groups
were sacrificed to obtain the foetuses. Pb level in the maternal and foetal blood
and cerebellum was estimated by spectrophotometry. Specimens of the cerebellum of
different mother and foetal groups were processed to histological and
immunohistochemical staining for microscopic examination. RESULTS: The results
showed that administration of Pb to pregnant rats resulted in a dose-dependent
toxicity for both mothers and foetuses in the form of decrease in maternal weight
gain, placental and foetal weights, brain weight and diminished foetal growth
parameters, which were prominent in rat's group treated with larger dose of Pb.
In Pb-treated rats, Pb level in blood and cerebellum was high when compared with
the control group. The histopathological examination of the cerebellum of treated
dams and foetuses showed marked alterations mainly in the form of Purkinje cell
degeneration and lack of development of foetal cerebellum. Co-treatment of garlic
extract along with Pb resulted in a significant decrease in Pb levels as compared
with those treated with Pb alone with improvement of the histopathological
changes. CONCLUSIONS: This study was useful in evaluating the hazardous effects
of uncontrolled use of Pb in general and in assessing the developmental and
neurotoxicity of foetuses due to exposure during pregnancy in particular. Co
administration of garlic has beneficial effects in amelioration of Pb-induced
neurotoxicity and reversing the histopathological changes of the cerebellum of
mother rats and foetuses. (Folia Morphol 2018; 77, 1: 1-15).
PMID- 28703847
TI - Variability and constraint of vertebral formulae and proportions in colugos, tree
shrews, and rodents, with special reference to vertebral modification by
aerodynamic adaptation.
AB - BACKGROUND: The aim of the present study is to provide the first large data set
on vertebral formulae and proportions, and examine their relationship with
different locomotive modes in colugos (Dermoptera), tree shrews (Scandentia), and
rodents (Rodentia), which have been considered less variable because they were
thought to have a plesiomorphic number of 19 thoracolumbar vertebrae. MATERIALS
AND METHODS: The data included 33 colugos and 112 tree shrews, which are
phylogenetically sister taxa, and 288 additional skeletons from 29 other
mammalian species adapted to different locomotive modes, flying, gliding,
arboreal, terrestrial, digging, and semi-aquatic habitats. RESULTS: The following
results were obtained: (1) intra-/interspecies variability and geographical
variation in thoracic, lumbar, and thoracolumbar counts were present in two
gliding colugo species and 12 terrestrial/arboreal tree shrew species; (2) in our
examined mammals, some aerodynamic mammals, such as colugos, southern flying
squirrels, scaly-tailed squirrels, and bats, showed exceptionally high amounts of
intraspecific variation of thoracic, lumbar, and thoracolumbar counts, and sugar
gliders and some semi-aquatic rodents also showed some variation; (3) longer
thoracic and shorter lumbar vertebrae were typically shared traits among the
examined mammals, except for flying squirrels (Pteromyini) and scaly-tailed
squirrels (Anomaluridae). CONCLUSIONS: Our study reveals that aerodynamic
adaptation could potentially lead to strong selection and modification of
vertebral formulae and/or proportions based on locomotive mode despite
evolutionary and developmental constraints. (Folia Morphol 2018; 77, 1: 44-56)
Background: The aim of the present study is to provide the first large data set
on vertebral formulae and proportions, and examine their relationship with
different locomotive modes in colugos (Dermoptera), tree shrews (Scandentia), and
rodents (Rodentia), which have been considered less variable because they were
thought to have a plesiomorphic number of 19 thoracolumbar vertebrae. MATERIALS
AND METHODS: The data included 33 colugos and 112 tree shrews, which are
phylogenetically sister taxa, and 288 additional skeletons from 29 other
mammalian species adapted to different locomotive modes, flying, gliding,
arboreal, terrestrial, digging, and semi-aquatic habitats. RESULTS: The following
results were obtained: (1) intra-/interspecies variability and geographical
variation in thoracic, lumbar, and thoracolumbar counts were present in two
gliding colugo species and 12 terrestrial/arboreal tree shrew species; (2) in our
examined mammals, some aerodynamic mammals, such as colugos, southern flying
squirrels, scaly-tailed squirrels, and bats, showed exceptionally high amounts of
intraspecific variation of thoracic, lumbar, and thoracolumbar counts, and sugar
gliders and some semi-aquatic rodents also showed some variation; (3) longer
thoracic and shorter lumbar vertebrae were typically shared traits among the
examined mammals, except for flying squirrels (Pteromyini) and scaly-tailed
squirrels (Anomaluridae). CONCLUSIONS: Our study reveals that aerodynamic
adaptation could potentially lead to strong selection and modification of
vertebral formulae and/or proportions based on locomotive mode despite
evolutionary and developmental constraints. (Folia Morphol 2018; 77, 1: 44-56).
PMID- 28703848
TI - Distal root curvatures in mandibular molars: analysis using digital panoramic X
rays.
AB - BACKGROUND: The aim of this study was to describe the degree of curvature in
distal roots in the first and second permanent mandibular molars in a Chilean
patient sample. A cross-sectional descriptive study was conducted in which
digital panoramic X-rays were analysed. MATERIALS AND METHODS: Examinations of
patients under 18 years, with signs of distortion or alteration in the contrast
or the presence of pathologies that affected visualisation of the roots and pulp
chamber floor of the teeth to be analysed were excluded. Using the AutoCad
software, an angle was drawn to represent the curve of the root in its different
thirds, drawing lines inside the root canal from the pulp-chamber floor to the
dental apex. Using the classic definition of dilaceration (root curvature > 90
degrees ), its prevalence was established. 412 teeth and roots were analysed,
finding a dilaceration prevalence of 0.73% (n = 3). 84.72% of the roots presented
some type of curvature. RESULTS: The middle third had the highest percentage of
curvatures and the greatest average of angular curvature, whereas the cervical
third was the straightest. No significant differences were found between the
degree of curvature and the gender of the subjects, except for the apical third
of tooth 3.6. The analysis of curvature by root third offers to the clinician a
better perspective of the directional change of the roots and does not limit it
to just the presence of curves in the apical third. CONCLUSIONS: The report of
the angular degree of the curvatures, in addition to the prevalence of
dilacerations, informs to the clinicians about the likelihood of finding
difficulties when treating root canals. (Folia Morphol 2018; 77, 1: 131-137).
PMID- 28703849
TI - The supreme turbinate and the drainage of the posterior ethmoids: a computed
tomographic study.
AB - BACKGROUND: It is generally acknowledged that the posterior ethmoidal cells drain
under the superior nasal turbinate (SorNT) or, rarely, under the supreme nasal
turbinate (SmeNT), and the sphenoid ostium (SO) opens to the sphenoethmoidal
recess. However, detailed relations between these structures are variable,
complex and still not clear. There is no reliable data on the prevalence of SmeNT
and drainage of the posterior ethmoidal cells under this structure. The aim of
this study was to re-evaluate the anatomy of the aforementioned region. MATERIALS
AND METHODS: Multiplanar and three-dimensional reconstruction analysis of 100
thin slice paranasal sinus computed tomography scans. RESULTS: SmeNT was
identified in 77 subjects (136 sides). It formed the ostium to the posterior
ethmoidal cell adjacent to the skull base or orbit in 58 subjects (91 sides).
This cell drained independently from the remaining posterior ethmoidal cells. The
sphenoethmoidal (Onodi) cell drained to supreme meatus in 41 subjects (54 sides),
and to superior meatus in 37 subjects (49 sides). SO was always located medial to
the posteroinferior attachment of SmeNT, or SorNT (in absence of SmeNT).
CONCLUSIONS: Patients with divergent drainage of the posterior ethmoids (with
posterior ethmoidal cell draining to the supreme meatus) may require more
extensive surgery to avoid persistence or recurrence of inflammatory disease.
SmeNT is more common than thought, but due to its posterior and superior location
to SorNT, it is rarely seen intraoperatively. If SmeNT is present, SO is always
located medial to its posteroinferior attachment. (Folia Morphol 2018; 77, 1: 110
115).
PMID- 28703850
TI - The size of the foramen ovale regarding to the presence and absence of the
emissary sphenoidal foramen: is there any relationship between them?
AB - BACKGROUND: The study investigates the size of the foramen ovale (FO) in relation
to the presence and absence of the emissary sphenoidal foramen (ESF). Any
possible alteration of the FO size in relation to the ESF (unilateral or
bilateral) presence and absence was also examined. MATERIALS AND METHODS: One
hundred and ninety-five (117 male and 78 female) Greek adult dry skulls were
investigated. RESULTS: The ESF was present in 40% of the skulls (21.5%
bilaterally and 18.5% unilaterally). No statistical significant difference was
detected between ESF presence or absence and its unilateral or bilateral
occurrence. The ESF existence had no relation to the FO size. CONCLUSIONS: The
ESF absence or presence has no effect on FO size. The emissary sphenoidal vein is
an additional venous pathway connecting cavernous sinus with the pterygoid venous
plexus. These findings enhance that the venous plexus of the FO is a constant
trait. The meticulous knowledge of the middle cranial fossa anatomy is of
paramount importance during transovale procedures, as the outcome of cannulation
may be affected by the existence of ESF, the confluence FO-ESF, the existence of
osseous spurs and bridging into the FO. (Folia Morphol 2018; 77, 1: 90-98).
PMID- 28703851
TI - Anatomy and morphometry of the distal gracilis muscle tendon in adults and
foetuses.
AB - Ten human gracilis muscles obtained from adults and ten gracilis muscles
collected from human foetuses between the 15th and 21st week of gestation were
examined. The results of this preparatory study show that the gracilis muscle in
adults is narrow and long - 482 mm on average. The distal tendon of gracilis
muscle is long, 294 mm on average. It can be divided into two sections - external
part, outside the muscle belly, and internal, intramuscular, part. The latter one
is partially covered by muscle fibres and some of it is completely hidden inside
the muscle belly, which is on average 76 mm long. Presence of an intramuscular
part of the distal tendon was also demonstrated in the foetal material. Moreover,
very strong correlations between particular muscle lengths were noted in
foetuses. (Folia Morphol 2018; 77, 1: 138-143).
PMID- 28703852
TI - A rare vascular anomaly in the form of double left brachiocephalic vein detected
incidentally during cardiac implantable electronic device (CIED) placement.
AB - The growing number of transvenous cardiac implantable electronic device (CIED)
implantation procedures helps detect rare vascular anomalies. Genetic
disturbances in vascular development can produce systemic vein anomalies,
including the left brachiocephalic vein (BCV). BCV anomalies commonly coexist
with a persistent left superior vena cava (PLSVC), detected in 0.3-0.5% of the
general population. The three known anatomical variations of PLSVC are two
variations involving a BCV bridge and the third with BCV agenesis. BCV anomalies
occur in 1% of patients with congenital heart defects, whereas the estimated
proportion of BCV anomalies in the population with no cardiovascular symptoms is
below 0.4%. A rarely observed, and thus rarely reported, BCV variation is a
double left BCV, with the additional vessel typically found inferior and
posterior to the ascending aorta prior to draining into the superior vena cava.
This case report presents a previously unreported variation of double left BCV,
with both vessels coursing parallel to each other, superior to the aortic arch.
(Folia Morphol 2018; 77, 1: 161-165).
PMID- 28703853
TI - Zika, Ebola, and Age: Global and Cellular Aging and Their Catalytic Effect on
These Infections.
PMID- 28703854
TI - Kernel oil content and oil composition in walnut (Juglans regia L.) accessions
from north-eastern Italy.
AB - BACKGROUND: Walnut oil use is currently limited by its poor oxidative stability
due to the high percentage of polyunsaturated fatty acids. Modifying the oil
composition may be a goal in walnut breeding to increase interest in this crop.
Exploring natural variability and identifying the main environmental factors
affecting oil quality are necessary in crop selection. Therefore 190 wild
accessions were collected and evaluated during 2013 and 2014 for oil content and
its fatty acid profile and compared with five commercial cultivars as references.
RESULTS: High variation in kernel oil content and fatty acid composition was
found in the native walnut. Kernel oil content ranged from 54.2 to 72.2% (w/w).
The major fatty acids were linoleic (range 46.9-68.6%), oleic (10.0-25.1%),
linolenic (6.9-17.6%), palmitic (3.9-11.4%) and stearic (1.1-5.2%) acids. Some
accessions had oil with a fatty acid ratio very different from the reference
commercial cultivars, especially the oleic acid/polyunsaturated fatty acid (PUFA)
ratio. A significant linear relationship and positive correlation between the
daily minimum temperature and oleic acid content was observed in the wild
walnuts. CONCLUSION: The wide variation in fatty acid content and composition
allows superior accessions to be selected for diffusion among growers. A suitable
strategy would be to make a selection against PUFA content rather than just for
high oleic acid. In addition, the selected high oleic accessions, before being
utilized per se or as donor parents in breeding programs, have to demonstrate
they are not adversely affected by the environment. (c) 2017 Society of Chemical
Industry.
PMID- 28703855
TI - D antibodies in pregnant women in multiethnic Suriname: the observational RheSuN
study.
AB - BACKGROUND: Maternal antibodies against the D antigen are the most common cause
of severe hemolytic disease of the fetus and newborn (HDFN). In high-income
countries, the risk of D immunization has been reduced by routine antenatal and
postpartum administration of RhIG from 13% to less than 0.5%. In less-resourced
countries, such as Suriname, red blood cell (RBC) antibody screening during
pregnancy and prophylactic RhIG administration are not routine. Accurate data on
D immunization risk is not available. In the RheSuN (Rhesus Surinamese Neonates)
study, the prevalence and the hemolytic potential of maternal D antibodies were
investigated. STUDY DESIGN AND METHODS: A multicenter cross-sectional study in
four major hospitals in Paramaribo, Suriname, covering 90% of approximately
10,000 births yearly in Suriname. Included were D- pregnant women of various
ethnicities seeking routine prenatal care and/or their newborns. RESULTS: D
antibodies were detected in 19 of 214 D- pregnancies (8.9%; 95% confidence
interval, 5.1%-12.7%), in 2.0% of primigravid and 11.7% of multigravid women. The
direct antiglobulin test was positive in 11 of 13 tested D+ newborns.
Determination of D antibody titers and antibody-dependent cell mediated
cytotoxicity (ADCC) assay revealed three newborns at high risk for HDFN (ADCC >
50%). CONCLUSION: D immunization risk in Suriname women is comparable to the pre
anti-D prophylaxis era in high-income countries. Recommended is free-of-charge
routine RBC antibody screening and prophylactic RhIG administration for women at
risk for D antibody formation as part of standard of ante- and postnatal care.
PMID- 28703856
TI - tPA variant tPA-A296-299 Prevents impairment of cerebral autoregulation and
necrosis of hippocampal neurons after stroke by inhibiting upregulation of ET-1.
AB - Tissue-type plasminogen activator (tPA) is neurotoxic and exacerbates uncoupling
of cerebral blood flow (CBF) and metabolism after stroke, yet it remains the sole
FDA-approved drug for treatment of ischemic stroke. Upregulation of c-Jun
terminal kinase (JNK) after stroke contributes to tPA-mediated impairment of
autoregulation, but the role of endothelin-1 (ET-1) is unknown. Based on the
Glasgow Coma Scale, impaired autoregulation is linked to adverse outcomes after
TBI, but correlation with hippocampal histopathology after stroke has not been
established. We propose that given after stroke, tPA activates N-Methyl-D
Aspartate receptors (NMDA-Rs) and upregulates ET-1 in a JNK dependent manner,
imparing autoregulation and leading to histopathology. After stroke, CBF was
reduced in the hippocampus and reduced further during hypotension, which did not
occur in hypotensive sham pigs, indicating impairment of autoregulation.
Autoregulation and necrosis of hippocampal CA1 and CA3 neurons were further
impaired by tPA, but were preserved by the ET-1 antagonist BQ 123 and tPA-A,296
299 a variant that is fibrinolytic but does not bind to NMDA-Rs. Expression of ET
1 was increased by stroke and potentiated by tPA but returned to sham levels by
tPA-A296-299 and the JNK antagonist SP600125. Results show that JNK releases ET-1
after stroke. Tissue-type plasminogen activator -A296-299 prevents impairment of
cerebral autoregulation and histopathology after stroke by inhibiting
upregulation of ET-1.
PMID- 28703857
TI - Comparison of two external fixator systems for fracture reduction during
minimally invasive plate osteosynthesis in simulated antebrachial fractures.
AB - OBJECTIVE: To compare the Minimally Invasive Reduction Instrumentation System
(MIRIS) to a two-ring circular fixator construct (CFC) for indirect reduction
during minimally invasive plate osteosynthesis. STUDY DESIGN: Cadaveric
antebrachial fracture model. ANIMALS: Ten skeletally mature dog cadavers.
METHODS: Simulated bilateral antebrachial fractures were reduced and stabilized
with the MIRIS on one limb, and a CFC on the contralateral limb, prior to placing
a 10 hole Locking Compression Plate. Time to satisfactory reduction and implant
placement were compared. Difficulty of fracture reduction and plate application
was subjectively scored (1 to 5) for each procedure. Prefracture and
postoperative orthogonal antebrachial radiographs were compared to assess
restoration of radial length and angulation in sagittal and frontal planes. A
paired t test (P <= .05) was used to compare parameters between the two reduction
techniques. RESULTS: Reduction was faster (P = .0191) and plate application was
subjectively easier (P = .047) when using the MIRIS compared to the CFC. There
were no differences in subjective difficulty of reduction or plate application
time between techniques. Mean postoperative radial length was reduced by
approximately 4-mm, and procurvatum were decreased by approximately 7 degrees
compared to prefracture measurements, regardless of reduction technique.
CONCLUSION: The MIRIS allowed for faster fracture reduction, and simplified plate
placement compared to a temporary application of a CFC in our simulated
antebrachial fracture model.
PMID- 28703858
TI - Traction-assisted colorectal endoscopic submucosal dissection using the
Mucosectom2 device.
PMID- 28703859
TI - The operational implications of donor behaviors following enrollment in STRIDE
(Strategies to Reduce Iron Deficiency in blood donors).
AB - BACKGROUND: Donor behaviors in STRIDE (Strategies to Reduce Iron Deficiency), a
trial to reduce iron deficiency, were examined. STUDY DESIGN AND METHODS: Six
hundred ninety-two frequent donors were randomized to receive either 19 or 38 mg
iron for 60 days or an educational letter based on their predonation ferritin.
Compliance with assigned pills, response to written recommendations, change in
donation frequency, and future willingness to take iron supplements were
examined. RESULTS: Donors who were randomized to receive iron pills had increased
red blood cell donations and decreased hemoglobin deferrals compared with
controls or with pre-STRIDE donations. Donors who were randomized to receive
educational letters had fewer hemoglobin deferrals compared with controls. Of
those who received a letter advising of low ferritin levels with recommendations
to take iron supplements or delay future donations, 57% reported that they
initiated iron supplementation, which was five times as many as those who
received letters lacking a specific recommendation. The proportion reporting
delayed donation was not statistically different (32% vs. 20%). Of donors who
were assigned pills, 58% reported taking them "frequently," and forgetting was
the primary reason for non-compliance. Approximately 80% of participants
indicated that they would take iron supplements if provided by the center.
CONCLUSIONS: Donors who were assigned iron pills had acceptable compliance,
producing increased red blood cell donations and decreased low hemoglobin
deferrals compared with controls or with pre-STRIDE rates. The majority of donors
assigned to an educational letter took action after receiving a low ferritin
result, with more donors choosing to take iron than delay donation. Providing
donors with information on iron status with personalized recommendations was an
effective alternative to directly providing iron supplements.
PMID- 28703860
TI - Transient hemolysis due to anti-D and anti-A1 produced by engrafted donor's
lymphocytes after allogeneic unmanipulated haploidentical hematopoietic stem cell
transplantation.
AB - BACKGROUND: Development of de novo alloantibodies against recipient's red blood
cell (RBC) antigens by engrafted donor's lymphocytes is a known phenomenon in the
setting of allogeneic hematopoietic stem cell transplantation (HSCT). This
situation is usually clinically insignificant. We report a case of early
clinically relevant hemolytic anemia in a blood group A1 D+ patient, due to a
limited production of anti-D and anti-A1 produced by nonpreviously sensitized
newly engrafted donor's immune system. CASE REPORT: A 31-year-old Caucasian
woman, blood group A1 , D+, with Hodgkin's lymphoma, received an unmanipulated
haploidentical allogeneic peripheral blood HSCT after a nonmyeloablative
conditioning regimen. Donor blood group was A2 B, D-. The patient had an
uneventful course until Day +34, when she developed clinically significant
hemolytic anemia with a positive direct antiglobulin test. Anti-D and anti-A1
produced by the donor-engrafted lymphocytes were detected both in serum and in
eluate. The hemolysis produced an accelerated group change, turning the patient's
ABO group into A2 B 2 weeks after the detection of the alloantibodies. As the
residual patient's RBCs progressively disappeared, anti-D and anti-A1 production
decreased and were not detected in serum by Day +41. CONCLUSION: This case
illustrates that de novo alloantibody production against ABO and D antigens by
the newly engrafted donor's lymphocytes can occasionally cause clinically
significant anemia. To our knowledge, this is the first case reported of
clinically significant hemolytic anemia due to a transient anti-D anti-A1
alloimmunization after T-cell-repleted haploidentical HSCT.
PMID- 28703861
TI - Platelet storage performance is consistent by donor: a pilot study comparing
"good" and "poor" storing platelets.
AB - BACKGROUND: In retrospective studies, it has been shown that differences in
storage variables of platelet (PLT) concentrates (PCs) are partially donor
dependent. It was our aim to prospectively determine the donor effect on PLT
quality. STUDY DESIGN AND METHODS: Based on quality control data of outdated
apheresis PCs, male donors were selected with at least one PC with a pH value of
more than 7.0 ("good," n = 6) or one PC with a pH value of less than 6.7 ("poor,"
n = 6) on Day 8. These donors donated a PC (Trima Accel, Terumo) and completed a
short questionnaire about their health and lifestyle. PCs were stored for 12 days
and analyzed at regular intervals for in vitro quality. RESULTS: Donor
characteristics were comparable, except that zero of six good and four of six
poor donors reported high blood pressure and/or high cholesterol/fat and/or use
of medicines. Lactate production in good PCs was lower than that in poor PCs
(0.09 +/- 0.03 mmol/day/1011 PLTs vs. 0.13 +/- 0.04 mmol/day/1011 PLTs, p < 0.05)
resulting in a higher pH from Day 5 onward. At the end of storage, the good PCs
showed lower CD62P expression, lower phosphatidylserine exposure, and higher
mitochondrial membrane potential. PLT functional properties were only slightly
different. Despite having lower pH, the poor PCs also fulfilled European
Guidelines during 7-day storage. CONCLUSION: Platelet storage performance is
consistent when donors are dichotomized as having good or poor storing PLTs.
Metabolic differences are perhaps due to different functionality of the
mitochondria. More research is needed to establish the underlying causes and the
implications for donors and blood products.
PMID- 28703862
TI - Addressing the risk of bacterial contamination in platelets: a hospital economic
perspective.
AB - BACKGROUND: Bacterially contaminated platelets (PLTs) remain a serious risk. The
Food and Drug Administration has issued draft guidance recommending hospitals
implement secondary testing or transfuse PLTs that have been treated with
pathogen reduction technology (PRT). The cost implications of these approaches
are not well understood. STUDY DESIGN AND METHODS: We modeled incurred costs when
hospitals acquire, process, and transfuse PLTs that are PRT treated with
INTERCEPT (Cerus Corp.) or secondary tested with the PLT PGD Test (Verax
Biomedical). RESULTS: Hospitals will spend $221.27 (30.0%) more per PRT-treated
apheresis PLT unit administered compared to a Zika-tested apheresis PLT unit that
is irradiated and PGD tested in hospital. This difference is reflected in PRT PLT
units having: 1) a higher hospital purchase price ($100.00 additional charge
compared to an untreated PLT); 2) lower therapeutic effectiveness than untreated
PLTs among hematologic-oncologic patients, which contributes to additional
transfusions ($96.05); or 3) fewer PLT storage days, which contributes to higher
outdating cost from expired PLTs ($67.87). Only a small portion of the
incremental costs for PRT-treated PLTs are offset by costs that may be avoided,
including primary bacterial culture, secondary bacterial testing ($26.65),
hospital irradiation ($8.50), Zika testing ($4.47), and other costs ($3.03).
CONCLUSION: The significantly higher cost of PRT-treated PLTs over PGD-tested
PLTs should interest stakeholders. For hospitals that outdate PLTs, savings
associated with expiration extension to 7 days by adding PGD testing will likely
be substantially greater than the cost of implementing PGD-testing. Our findings
might usefully inform a hospital's decision to select a particular blood safety
approach.
PMID- 28703863
TI - Effect of sodium-glucose co-transporter-2 inhibitors on impaired ventricular
repolarization in people with Type 2 diabetes.
AB - AIMS: To test the hypothesis that treatment with a sodium-glucose co-transporter
2 inhibitor would reverse ventricular repolarization heterogeneity, a predictor
of cardiovascular mortality, in people with Type 2 diabetes. METHODS: We
retrospectively analysed changes in indices of ventricular repolarization before
and after treatment with a sodium-glucose co-transporter-2 inhibitor in 46 people
with Type 2 diabetes. RESULTS: Sodium-glucose co-transporter-2 inhibitor
treatment reduced HbA1c concentration [62+/-13 mmol/mol (7.7+/-1.2%) vs 59+/-16
mmol/mol (7.5+/-1.4%)], body weight (77.8+/-13.9 vs 74.7+/-12.5 kg) and systolic
blood pressure (133+/-18 vs 126+/-12 mmHg) in the study participants. Heart rate
and QTc interval were not changed by sodium-glucose co-transporter-2 inhibitor
treatment, but QTc dispersion was significantly reduced (median, 48.8 vs 44.2
ms). Sodium-glucose co-transporter-2 inhibitor treatment reversed QTc dispersion
more in participants who had larger QTc dispersion before the treatment. Changes
in systolic blood pressure (Spearman's rho= 0.319; P=0.031), but not in HbA1c
concentration, were correlated with changes in QTc dispersion after sodium
glucose co-transporter-2 inhibitor treatment. CONCLUSIONS: The findings suggest
that sodium-glucose co-transporter-2 inhibitor treatment reverses ventricular
repolarization heterogeneity in people with Type 2 diabetes, independently of its
effect on glycaemic control. The favourable effect on ventricular repolarization
heterogeneity could be the mechanism by which empaglifozin reduced cardiovascular
events in a recent study.
PMID- 28703864
TI - Effect of a peptide in cosmetic formulations for hair volume control.
AB - OBJECTIVE: The capacity of hair to absorb water causes changes in its physical
and cosmetic properties under different environmental conditions. Hence, the
control of hair volume in variable relative humidity settings is an important
topic in cosmetics. The behaviour of two types of hair, Caucasian and Asian, was
studied regarding their volume change in different relative humidity conditions.
The ability of a peptide as a hair volume treatment was evaluated in two climate
control formulations. METHODS: Tresses of the two types of hair were tested in
two relative humidity (RH) conditions: (A) variable relative humidity (2 h 40%
RH, followed by 2 h 90% RH and 2 h of 40% RH), and (B) continuous high relative
humidity (90% RH for 6 h). Changes in the hair tress volume were assessed
throughout time. Hair treated with two climate control formulations, with and
without a peptide (KP peptide), were tested under the two relative humidity
conditions. RESULTS: Caucasian hair had a higher change in volume compared to the
Asian hair in variable and high relative humidity conditions. The hair volume
increase when subject to high air humidity, and it was lower with the
incorporation of a peptide into climate control formulations. CONCLUSION:
Caucasian hair showed higher volume than Asian hair when submitted to both
relative humidity conditions. The incorporation of the peptide into the climate
control formulations, a base (mostly composed of water ~ 94%) and an ethanolic,
was found to reduce the volume of Caucasian hair tresses. The presence of the
peptide improved the hair volume change more than 60% in high relative humidity
conditions.
PMID- 28703865
TI - Identification of unique proteomic signatures in allergic and non-allergic skin
disease.
AB - BACKGROUND: Atopic dermatitis (AD), psoriasis (PS), and contact dermatitis (CD)
are common skin diseases, characterized by barrier disruption and systemic
inflammation, with unique epidermal signatures and common inflammatory pathways
identified by transcriptomic profiling. This study profiled proteomic signatures
in serum from subjects with AD, PS, and CD compared with healthy controls (HC).
OBJECTIVE: Identify unique proteomic signatures to distinguish between
inflammatory diseases with similar epidermal disruption and overlapping
epithelial inflammation. METHODS: Sera from 20 subjects with moderate to severe
AD, 10 subjects with CD, 12 subjects with moderate to severe PS, 10 subjects with
both AD and CD, and 10 HC with no history of skin disease was analysed using high
throughput proteomic analysis that detects expression of 1129 protein targets.
Protein expression was compared between disease and HC, and across diseases for
statistical significance (fold change>=1.5 and false discovery rate<=0.05), to
identify unique proteomic signatures for each disease. RESULTS: Complement C5A
anaphylatoxin (C5A), lipopolysaccharide binding protein (LBP), C-reactive protein
(CRP), ILT-4, C-C motif ligand 18 (PARC), and sialic acid-binding Ig-like lectin
14 (SIG14) were significantly modulated in all three diseases compared with HC.
We identified unique signatures for AD (Immunoglobulin E (IgE), thymus- and
activation-regulated chemokine (TARC) and macrophage-derived chemokine (MDC)), CD
(10 proteins), and PS (kynureninase (KYNU)). Proteomic profiling in subjects with
both AD and CD identified additional dysregulated proteins compared with subjects
with either condition alone, indicating an exacerbated inflammation reaction.
CONCLUSIONS AND CLINICAL RELEVANCE: Unique sera proteomic signatures may
distinguish between inflammatory skin diseases despite similar epidermal barrier
disruption and epithelial inflammation. This may provide insight into disease
pathogenesis, diagnosis, and therapeutic intervention in difficult-to-treat
subjects.
PMID- 28703866
TI - A Holmium(III)-Based Single-Molecule Magnet with Pentagonal-Bipyramidal Geometry.
AB - The right environment: The remarkable properties of a recently reported
holmium(III)-based single-ion magnet have been ascribed to the hyperfine
interactions with the half-integer nuclear spin in combination with the
pentagonal-bipyramidal coordination environment. These results provide insight
into the complicated magnetic properties of nanosized magnetic materials.
PMID- 28703867
TI - Diabetes and risk of occupational injury: a cohort study.
AB - AIMS: To investigate if diabetes is associated with a higher risk of occupational
(workplace or commuting) injury. METHODS: Medication data from the Finnish
Prescription Register were used to identify diabetes cases in 2004 in a large
employee cohort (the Finnish Public Sector study). These data were linked to
injury records obtained from the Federation of Accident Insurance Institutions. A
total of 1020 diabetes cases (median age 52 years, range 20 to 65 years; 66%
women) and their 5234 age- and sex-matched controls were followed up until 2011.
Sex-stratified Cox proportional hazards models, adjusting for age, occupational
status, obesity and health behaviours, were applied. Because of the small number
of men in the cohort, injury types and locations were only examined among women.
RESULTS: During the median follow-up of 6.7 years, 25% of the participants with
diabetes (n=252) and 20% of those without (n=1051) experienced an occupational
injury. The association between diabetes and injury was stronger in women than
men (P=0.048). Diabetes was associated with a higher risk of workplace (hazard
ratio 1.37, 95% CI 1.11 to 1.69) and commuting (hazard ratio 1.36, 95% CI 1.03 to
1.79) injury in women. With regard to different injury types and locations,
diabetes was associated with bone fractures, dislocations, sprains and strains,
and injuries to upper and lower extremities. In men, there was an association
between insulin-treated diabetes and commuting injury (hazard ratio 3.14, 95% CI
1.52 to 6.49). CONCLUSIONS: Diabetes was associated with workplace and commuting
injuries in women. Men with insulin-treated diabetes had a higher risk of
commuting injuries.
PMID- 28703868
TI - Cardiac vagal tone, a non-invasive measure of parasympathetic tone, is a
clinically relevant tool in Type 1 diabetes mellitus.
AB - AIMS: To compare a novel index of parasympathetic tone, cardiac vagal tone, with
established autonomic variables and to test the hypotheses that (1) cardiac vagal
tone would be associated with established time and frequency domain measures of
heart rate and (2) cardiac vagal tone would be lower in people with Type 1
diabetes than in a matched healthy cohort and lower still in people with
established neuropathy. METHODS: Cardiac vagal tone is a validated
cardiometrically derived index of parasympathetic tone. It is measured using a
standard three-lead electrocardiogram which connects, via Bluetooth, to a
smartphone application. A 5-min resting recording of cardiac vagal tone was
undertaken and observational comparisons were made between 42 people with Type 1
diabetes and peripheral neuropathy and 23 without peripheral neuropathy and 65
healthy people. In those with neuropathy, 24-h heart rate variability values were
compared with cardiac vagal tone. Correlations between cardiac vagal tone and
clinical variables were also made. RESULTS: Cardiac vagal tone was lower in
people with established neuropathy and Type 1 diabetes in comparison with healthy
participants [median (interquartile range) linear vagal scale 3.4 (1.6-5.5 vs 7.0
(5.5-9.6); P < 0.0001]. Cardiac vagal tone was positively associated with time (r
= 0.8, P < 0.0001) and frequency domain markers of heart rate variability (r =
0.75, P < 0.0001), representing established measures of parasympathetic function.
Cardiac vagal tone was negatively associated with age (r=-0.32, P = 0.003),
disease duration (r=-0.43, P < 0.0001) and cardiovascular risk score (r=-0.32, P
= 0.006). CONCLUSIONS: Cardiac vagal tone represents a convenient, clinically
relevant method of assessing parasympathetic nervous system tone, potentially
facilitating the earlier identification of people with Type 1 diabetes who should
undergo formal autonomic function testing.
PMID- 28703869
TI - Early supported discharge services for people with acute stroke.
AB - BACKGROUND: People with stroke conventionally receive a substantial part of their
rehabilitation in hospital. Services have now been developed that offer people in
hospital an early discharge with rehabilitation at home (early supported
discharge: ESD). OBJECTIVES: To establish if, in comparison with conventional
care, services that offer people in hospital with stroke a policy of early
discharge with rehabilitation provided in the community (ESD) can: 1) accelerate
return home, 2) provide equivalent or better patient and carer outcomes, 3) be
acceptable satisfactory to patients and carers, and 4) have justifiable resource
implications use. SEARCH METHODS: We searched the Cochrane Stroke Group Trials
Register (January 2017), Cochrane Central Register of Controlled Trials (CENTRAL
2017, Issue 1) in the Cochrane Library (searched January 2017), MEDLINE in Ovid
(searched January 2017), Embase in Ovid (searched January 2017), CINAHL in EBSCO
(Cumulative Index to Nursing and Allied Health Literature; 1937 to December
2016), and Web of Science (to January 2017). In an effort to identify further
published, unpublished, and ongoing trials we searched six trial registries
(March 2017). We also performed citation tracking of included studies, checked
reference lists of relevant articles, and contacted trialists. SELECTION
CRITERIA: Randomised controlled trials (RCTs) recruiting stroke patients in
hospital to receive either conventional care or any service intervention that has
provided rehabilitation and support in a community setting with an aim of
reducing the duration of hospital care. DATA COLLECTION AND ANALYSIS: The primary
patient outcome was the composite end-point of death or long-term dependency
recorded at the end of scheduled follow-up. Two review authors scrutinised
trials, categorised them on their eligibility and extracted data. Where possible
we sought standardised data from the primary trialists. We analysed the results
for all trials and for subgroups of patients and services, in particular whether
the intervention was provided by a co-ordinated multidisciplinary team (co
ordinated ESD team) or not. We assessed risk of bias for the included trials and
used GRADE to assess the quality of the body of evidence. MAIN RESULTS: We
included 17 trials, recruiting 2422 participants, for which outcome data are
currently available. Participants tended to be a selected elderly group of stroke
survivors with moderate disability. The ESD group showed reductions in the length
of hospital stay equivalent to approximately six days (mean difference (MD) -5.5;
95% confidence interval (CI) -3 to -8 days; P < 0.0001; moderate-grade evidence).
The primary outcome was available for 16 trials (2359 participants). Overall, the
odds ratios (OR) for the outcome of death or dependency at the end of scheduled
follow-up (median 6 months; range 3 to 12) was OR 0.80 (95% CI 0.67 to 0.95, P =
0.01, moderate-grade evidence) which equates to five fewer adverse outcomes per
100 patients receiving ESD. The results for death (16 trials; 2116 participants)
and death or requiring institutional care (12 trials; 1664 participants) were OR
1.04 (95% CI 0.77 to 1.40, P = 0.81, moderate-grade evidence) and OR 0.75 (95% CI
0.59 to 0.96, P = 0.02, moderate-grade evidence), respectively. Small
improvements were also seen in participants' extended activities of daily living
scores (standardised mean difference (SMD) 0.14, 95% CI 0.03 to 0.25, P = 0.01,
low-grade evidence) and satisfaction with services (OR 1.60, 95% CI 1.08 to 2.38,
P = 0.02, low-grade evidence). We saw no clear differences in participants'
activities of daily living scores, patients subjective health status or mood, or
the subjective health status, mood or satisfaction with services of carers. We
found low-quality evidence that the risk of readmission to hospital was similar
in the ESD and conventional care group (OR 1.09, 95% CI 0.79 to 1.51, P = 0.59,
low-grade evidence). The evidence for the apparent benefits were weaker at one-
and five-year follow-up. Estimated costs from six individual trials ranged from
23% lower to 15% greater for the ESD group in comparison to usual care.In a
series of pre-planned analyses, the greatest reductions in death or dependency
were seen in the trials evaluating a co-ordinated ESD team with a suggestion of
poorer results in those services without a co-ordinated team (subgroup
interaction at P = 0.06). Stroke patients with mild to moderate disability at
baseline showed greater reductions in death or dependency than those with more
severe stroke (subgroup interaction at P = 0.04). AUTHORS' CONCLUSIONS:
Appropriately resourced ESD services with co-ordinated multidisciplinary team
input provided for a selected group of stroke patients can reduce long-term
dependency and admission to institutional care as well as reducing the length of
hospital stay. Results are inconclusive for services without co-ordinated
multidisciplinary team input. We observed no adverse impact on the mood or
subjective health status of patients or carers, nor on readmission to hospital.
PMID- 28703870
TI - A Bulky m-Terphenyl Cyclopentadienyl Ligand and Its Alkali-Metal Complexes.
AB - The synthesis of the new m-terphenyl-substituted cyclopentadienyl ligand
precursor 1-cyclopentadiene-2,6-bis(2,4,6-trimethylphenyl)benzene (TerMes CpH) is
described. The synthesis proceeds through the reaction of TerMes Li with
cobaltocenium iodide, followed by oxidation of the intermediate cobalt(I) species
to give the corresponding cyclopentadiene as a mixture of isomers. The
preparation and spectroscopic properties of the alkali-metal salts (Li-Cs) is
described, as well as structural information obtained by X-ray diffraction
studies for the lithium, potassium, and cesium analogues. Crystallographic data
demonstrate the ability of these new ligands to act as monoanionic chelates by
forming metal complexes with Cp-M-Ar bonding environments.
PMID- 28703871
TI - The role of experiential knowledge within attitudes towards genetic carrier
screening: A comparison of people with and without experience of spinal muscular
atrophy.
AB - PURPOSE: Autosomal recessive conditions, while individually rare, are a
significant health burden with limited treatment options. Population carrier
screening has been suggested as a means of tackling them. Little is known,
however, about the attitudes of the general public towards such carrier screening
and still less about the views of people living with candidate genetic diseases.
Here, we focus on the role that such experience has on screening attitudes by
comparing views towards screening of people with and without prior experience of
the monogenetic disorder, Spinal Muscular Atrophy. METHODS: An exploratory
sequential mixed methods design was adopted. In-depth qualitative interviews were
used to develop two surveys. The surveys addressed attitudes towards carrier
screening (pre-conceptual and prenatal) for SMA. PARTICIPANTS: 337 participants
with SMA experience completed the SMA Screening Survey (UK) and 336 participants
with no prior experience of SMA completed the UK GenPop Survey, an amended
version of the SMA Screening Survey (UK). RESULTS: The majority of both cohorts
were in favour of pre-conception and prenatal carrier screening, however people
with experience of type II SMA were least likely to support either. Key
differences emerged around perceptions of SMA, with those without SMA experience
taking a dimmer view of the condition than those with. CONCLUSION: This study
underscores the significance of prior experience with the condition to screening
attitudes. It highlights the need for accurate and high-quality educational
resources to support any future carrier screening programmes, that particularly
in relation to rare genetic disorders like SMA that will fall outside the remit
of everyday experience for the majority of the population.
PMID- 28703872
TI - Lymph node station ratio: Revised nodal category for resected esophageal squamous
cell carcinoma patients.
AB - OBJECTIVES: The objective of this study was to evaluate a revised nodal category
based on the value of the lymph node (LN) station ratio (SR, metastatic LN
stations/examined LN stations) in esophageal squamous cell carcinoma (ESCC)
patients. METHODS: Data were obtained from 857 ESCC patients who underwent
primary radical esophagectomy. Prognostic performance was evaluated using the
Harrell concordance index (C-index), Akaike information criterion (AIC), and
likelihood ratio chi2 test (LR chi2 test). RESULTS: Each subgroup among the SR
categories demonstrated discriminatory results, whereas no significant survival
difference was observed between the N2 versus N3 classifications under the AJCC
pN system. Using the AJCC TNM staging system, the survival curves separated
between stages IIIA-IIIB and IIIB-IVA. However, when the T-SR-M scheme category
was applied, the survival curves between stages IIA-IIB, IIIA-IIIB, and IIIB-IVA
were significantly different. Furthermore, both the SR category and the T-SR-M
staging system showed superior performance with higher C-index and LR chi2 test
values and lower AIC values compared with the pN category and TNM staging system,
respectively. CONCLUSIONS: Following radical esophagectomy, the SR category
demonstrated superior prognostic ability relative to the AJCC pN category in ESCC
patients.
PMID- 28703873
TI - Cryoballoon ablation in Chinese patients with paroxysmal atrial fibrillation: 1
year follow-up.
AB - OBJECTIVES: We assessed the effectiveness and safety of cryoballoon ablation
(CBA) in the Chinese population with paroxysmal atrial fibrillation (AF) with a 1
year follow-up and determined the association of early recurrence of atrial
tachyarrhythmias (ERAT) with late recurrence (LR). METHODS: A total of 114
patients (age 61 +/- 10 years, 78 males) with paroxysmal AF who underwent CBA
were consecutively enrolled. After procedures, patients were observed for 3 days
with continuous electrocardiogram monitoring in the hospital with routine follow
up visits at 3 months, 6 months, and 1 year. Documented atrial tachyarrhythmia
>30 seconds was defined as recurrence. ERAT was defined as any recurrence during
the first 3 months, and LR was recurrence between 3 and 12 months. RESULTS: With
the first 3 months as blanking period, 76% of patients were free of LR at 12
months. Five patients (4%) experienced complications, including phrenic nerve
palsy, stroke, and groin complications. Forty-five percent of patients had ERAT
in the first 3 months and 31% of patients had ERAT in the first 3 days. Patients
with ERAT had higher LR rate (LRR) than those without ERAT (43% vs 8%, P <
0.001). The LRR of patients with ERAT only in the first 3 days was lower than
those with ERAT both in the first 3 days and in 4-90 days (29% vs 64%, P =
0.036). CONCLUSIONS: CBA was an effective and safe treatment option for
paroxysmal AF. Patients with ERAT had higher LRR after CBA of AF. The time when
ERAT occurred had an impact on LRR.
PMID- 28703874
TI - The functional potential and active populations of the pit mud microbiome for the
production of Chinese strong-flavour liquor.
AB - The popular distilled Chinese strong-flavour liquor (CSFL) is produced by solid
fermentation in the ground pit. Microbes inhabiting in the pit mud (PM) on the
walls of the fermentation pit are responsible for the production of caproic acid
(CA) that determines the quality of CSFL to a large degree. However, little is
known about the active microbial populations and metabolic potential of the PM
microbiome. Here, we investigated the overall metabolic features of the PM
microbiome and its active microbial components by combining metagenomics and
MiSeq-sequencing analyses of the 16S rRNA genes from DNA and RNA (cDNA). Results
showed that prokaryotes were predominant populations in the PM microbiome,
accounting for 95.3% of total metagenomic reads, while eukaryotic abundance was
only 1.8%. The dominant prokaryotic phyla were Firmicutes, Euryarchaeota,
Bacteroidetes, Actinobacteria and Proteobacteria, accounting for 48.0%, 19.0%,
13.5%, 2.5% and 2.1% of total metagenomic reads respectively. Most genes encoding
putative metabolic pathways responsible for the putative CA production via chain
elongation pathway were detected. This indicated that the PM microbiome owned
functional potential for synthesizing CA from ethanol or lactate. Some key genes
encoding enzymes involved in hydrogenotrophic and acetoclastic methanogenesis
pathways were detected in the PM metagenome, suggesting the possible occurrence
of interspecies hydrogen transfer between CA-producing bacteria and methanogens.
The 16S rDNA and 16S rRNA profiles showed that the Clostridial cluster IV,
Lactobacillus, Caloramator, Clostridium, Sedimentibacter, Bacteroides and
Porphyromonas were active populations in situ, in which Clostridial cluster IV
and Clostridium were likely involved in the CA production. This study improved
our understandings on the active populations and metabolic pathways of the PM
microbiome involved in the CA synthesis in the CSFL fermentation.
PMID- 28703875
TI - Evaluation of BiliCareTM transcutaneous bilirubin device in Japanese newborns.
AB - BACKGROUND: Non-invasive transcutaneous bilirubin (TcB) monitoring has been
widely used to screen for hyperbilirubinemia. TcB measured using the recently
developed BiliCareTM system, however, has not been fully evaluated. METHODS: One
hundred and seven TcB measurements were obtained from 82 Japanese newborns >=35
weeks' gestational age within 2 weeks after birth. Measurements were taken at the
scaphoid fossa, conchal cavity, and lobe of the ear using BiliCare. BiliCare TcB
were compared with total serum bilirubin (TB) and TcB obtained using another
bilirubinometer (JM-105TM). RESULTS: Transcutaneous bilirubin measured at all
three sites significantly correlated with TB (r = 0.91, 0.93, and 0.93 at the
scaphoid fossa, conchal cavity, and lobe, respectively). The mean differences
were 0.1, -0.3, and 3.6 at the scaphoid fossa, conchal cavity, and lobe,
respectively. BiliCare TcB at the scaphoid fossa significantly correlated with
that using the JM-105 (r = 0.91). The mean difference was 0.0. BiliCare, however,
produced a significantly higher and lower TcB than the JM-105 for TB <7 and >=15
mg/dL, respectively. CONCLUSIONS: Transcutaneous bilirubin measurements taken at
the scaphoid fossa or conchal cavity using BiliCare were more reliable than those
at the earlobe. BiliCare TcB differed from those of the JM-105, for TB <7 or >=15
mg/dL.
PMID- 28703876
TI - Foundations of infants' social group evaluations.
AB - Previous research has suggested that infants exhibit a preference for familiar
over unfamiliar social groups (e.g., preferring individuals from their own
language group over individuals from a foreign language group). However, because
past studies often employ forced-choice procedures, it is not clear whether
infants' intergroup preferences are driven by positivity toward members of
familiar groups, negativity toward members of unfamiliar groups, or both. Across
six experiments, we implemented a habituation procedure to independently measure
infants' positive and negative evaluations of speakers of familiar and unfamiliar
languages. We report that by 1 year of age, infants positively evaluate
individuals who speak a familiar language, but do not negatively evaluate
individuals who speak an unfamiliar language (Experiments 1 and 2). Several
experiments rule out lower-level explanations (Experiments 3-6). Together these
data suggest that children's early social group preferences may be shaped by
positive evaluations of familiar group(s), rather than negative evaluations of
unfamiliar groups.
PMID- 28703877
TI - Biochemical and hematological evaluations of black howler monkeys (Alouatta
pigra) in highly degraded landscapes in Mexico.
AB - BACKGROUND: Loss and fragmentation of Neotropical primates' habitat can alter the
health and individual adaptation. Physiological parameters reflect health status
and individuals responses to the habitat conditions. METHODS: We captured six
wild adult females and six adult males of Alouatta pigra to evaluate their
physical condition (body mass, respiratory and heart rate, and rectal
temperature), hematology and blood chemistry on fragmentation habitat condition
at southeastern Mexico. RESULTS: The males weighed more than females, but the
female' temperature, respiratory rate, and heart rate were higher. Low values of
hemoglobin, hematocrit, and red blood cells suggest some degree of anemia in
these howler monkeys. Low levels of the total protein, albumin, albumin/globulin
Ratio, and low levels of blood urea nitrogen suggest that howler monkeys could
have protein and carbohydrate deficiencies. CONCLUSIONS: Howler monkeys living
under the highly degraded conditions at Balancan, Tabasco, could be showing
adaptability by modifying their physiology, hematology, and blood chemistry in
response to the conditions of their fragmented landscape.
PMID- 28703878
TI - Obstetric hemorrhage and safe blood for transfusion in Ethiopia: the challenges
of bridging the gap.
AB - BACKGROUND: Obstetric hemorrhage is a leading cause of maternal death in sub
Saharan Africa, and the shortage of blood for transfusion is a contributory
factor. In Ethiopia, the National Blood Bank Service continues to be confronted
with challenges in its efforts to ensure the availability of blood for health
care facilities. This paper reviews the available data on the contribution of
obstetric hemorrhage to maternal mortality and examines the current status of the
blood supply in Ethiopia. STUDY DESIGN AND METHODS: We reviewed the published
literature and data from the Ethiopian Federal Ministry of Health. To assess the
status of the current blood supply, we applied the five cornerstones of a safe
and effective blood donor service advocated by the World Health Organization.
RESULTS: Our review indicates that there are insufficient national data on the
prevalence of obstetric hemorrhage and the contribution of blood supply shortage
to maternal death. Also, transfusion safety may be compromised by inadequate
testing of donated blood and ineffective hospital transfusion policies.
CONCLUSION: To overcome the shortage of blood to treat obstetric hemorrhage, the
first step is to evaluate the demand and supply gap by acquiring comprehensive
data on the current status of the blood supply and the prevalence of obstetric
hemorrhage in Ethiopia. Subsequent steps would include the implementation of
transfusion policies, the optimization of whole blood collection, ensuring
quality-assured testing of donated blood, and the implementation of transfusion
guidelines for the appropriate use of blood products. Strategies for long-term,
viable solutions to maintain an adequate blood supply should be simultaneously
developed.
PMID- 28703880
TI - Performance of prognostic scores and staging systems in predicting long-term
survival outcomes after surgery for intrahepatic cholangiocarcinoma.
AB - INTRODUCTION: We sought to validate the commonly used prognostic models and
staging systems for intrahepatic cholangiocarcinoma (ICC) in a large multi-center
patient cohort. METHODS: The overall (OS) and disease free survival (DFS)
prognostic discriminatory ability of various commonly used models were assessed
in a large retrospective cohort. Harrell's concordance index (c-index) was used
to determine accuracy of model prediction. RESULTS: Among 1054 ICC patients,
median OS was 37.7 months and 1-, 3-, and 5-year survival, were 78.8%, 51.5%, and
39.3%, respectively. Recurrence of disease occurred in 454 (43.0%) patients with
a median DFS of 29.6 months. One-, 3- and 5- year DFS were 64.6%, 46.5 % and
44.4%, respectively. The prognostic models associated with the best OS prediction
were the Wang nomogram (c-index 0.668) and the Nathan staging system (c-index
0.639). No model was proficient in predicting DFS. Only the Wang nomogram
exceeded a c-index of 0.6 for DFS (c-index 0.602). The c-index for the AJCC
staging system was 0.637 for OS and 0.582 for DFS. CONCLUSIONS: While the Wang
nomogram had the best discriminatory ability relative to OS and DFS, no ICC
staging system or nomogram demonstrated excellent prognostic discrimination. The
AJCC staging for ICC performed reasonably, although its overall discrimination
was only modest-to-good.
PMID- 28703879
TI - Precarious maintenance of simple DNA repeats in eukaryotes.
AB - In this review, we discuss how two evolutionarily conserved pathways at the
interface of DNA replication and repair, template switching and break-induced
replication, lead to the deleterious large-scale expansion of trinucleotide DNA
repeats that cause numerous hereditary diseases. We highlight that these
pathways, which originated in prokaryotes, may be subsequently hijacked to
maintain long DNA microsatellites in eukaryotes. We suggest that the negative
mutagenic outcomes of these pathways, exemplified by repeat expansion diseases,
are likely outweighed by their positive role in maintaining functional repetitive
regions of the genome such as telomeres and centromeres.
PMID- 28703881
TI - A novel RUNX2 mutation in exon 8, G462X, in a patient with Cleidocranial
Dysplasia.
AB - To identify a novel mutation of Runx2 gene in Cleidocranial Dysplasia (CCD)
patients and to characterize the functional consequences of this mutation. The
subjects consisted of 12 Korean CCD patients. After oral epithelial cells were
collected using a mouthwash technique, genomic DNA was extracted. Screening for
Runx2 mutation was performed using direct sequencing of polymerase chain reaction
(PCR) products for exons 1-8. Restriction fragment length polymorphism (RFLP)
analysis was performed to confirm the novel mutation. For functional studies, we
performed luciferase assay for Runx2 transacting activity, cyclohexamide chase
assay for Runx2 protein stability, real-time PCR for mRNA level of Runx2
downstream bone marker genes, and alkaline phosphatase (ALP) staining assay in
mesenchymal stem cells for osteoblast differentiation. Of the 12 patients, seven
showed Runx2 mutations reported previously and four showed no mutation. A novel
mutation, G462X in exon 8, which was located in the C-terminus of
proline/serine/threonine-rich (PST) domain, was found in one patient. In the
luciferase assay, Runx2 transacting activity was decreased in Runx2-G462X
transfected cells. In the cyclohexamide chase assay, Runx2-G462X mutation reduced
the stability of Runx2 protein. Expression of the bone marker genes (osteocalcin,
ALP, Type I collagen alphaI, matrix metalloproteinase-13, bone sialoprotein, and
osteopontin) decreased in G462X-transfected cells. In the ALP staining assay,
osteoblast differentiation was reduced in Runx2-G462X overexpressed cell. The
G462X mutation might reduce the Runx2 transacting activity, lower the protein
stability, downgrade the expression of bone marker genes, and eventually diminish
osteoblast differentiation in CCD patients.
PMID- 28703882
TI - Centrifugal Lithography: Self-Shaping of Polymer Microstructures Encapsulating
Biopharmaceutics by Centrifuging Polymer Drops.
AB - Polymeric microstructures encapsulating biopharmaceutics must be fabricated in a
controlled environment to preserve the biological activity. There is increasing
demand for simple methods designed to preserve the biological activity by
utilizing the natural properties of polymers. Here, the paper shows that
centrifugal lithography (CL) can be used for the fabrication of such
microstructures in a single centrifugation, by engineering the self-shaping
properties of hyaluronic acid (HA). In this method, HA drops are self-shaped into
hourglass-microstructures to produce two dissolving microneedles (DMN), which
facilitate transdermal delivery via implantation on the skin. In addition,
tuberculin purified protein derivatives are encapsulated into HA DMNs under
refrigerated conditions (4 degrees C) during CL. Therefore, the tuberculin skin
test (TST) with the DMNs indicates minimal damage, as opposed to the case of TST
with traditional hypodermic needles. These findings on the fabrication of
polymeric microstructures with biopharmaceutics may trigger the development of
various biomedical devices and therapies.
PMID- 28703883
TI - Associations between cardiovascular disease and its risk factors with hearing
loss-A cross-sectional analysis.
AB - OBJECTIVES: To investigate the relationship between hearing loss and
cardiovascular disease risk factors. DESIGN: Cross-sectional study. METHODS:
Participants were recruited between May 2010 and December 2015 and answered a
health and risk factor questionnaire. Physical and biochemical assessments were
performed. SETTING: A community-based population. PARTICIPANTS: A total of 5107
participants born within the years 1946-1964 enrolled in the Busselton Healthy
Ageing Study. MAIN OUTCOME MEASURES: Hearing was assessed behaviourally through
the best ear pure-tone average (500, 1000, 2000, 4000 Hz), low-frequency average
(250, 500, 1000 Hz) and high-frequency average (4000, 8000 Hz). Self-reported
hearing loss, tinnitus and hyperacusis were assessed via questionnaire.
Cardiovascular risk factors were assessed via a patient-completed questionnaire
and objective measurements including blood pressure, body mass index, waist
circumference, lipid profile and glycated haemoglobin. RESULTS: Of the
participants, 54% were female, with the mean age of 58 years (range 45-69 years).
Age, sex and family history of hearing loss were consistently strong determinants
of hearing loss outcomes. After adjusting for these, obesity, current smoking,
peripheral arterial disease and history of cardiovascular disease were
significantly associated with pure-tone, low-frequency and high-frequency hearing
loss. In addition, high blood pressure, triglyceride and glycated haemoglobin
were significantly associated with low-frequency hearing loss. There was a graded
association between hearing loss and Framingham Risk Score for cardiovascular
risk (P<0.001). CONCLUSIONS: Established cardiovascular disease and individual
and combined cardiovascular disease risk factors were found to be associated with
hearing loss. Future research should prospectively investigate whether targeting
cardiovascular disease can prevent hearing loss.
PMID- 28703884
TI - Nasal compliance measurement for diagnosis of idiopathic non-allergic rhinitis: A
prospective case-controlled study of 63 patients.
PMID- 28703885
TI - Use of a 72-cm-long extended bilateral deep inferior epigastric artery perforator
free flap for reconstruction of a lower leg with no suitable recipient vessel
around the injury zone: A case report.
AB - In free-flap reconstruction of the lower extremity, due either to trauma or pre
existing vascular disease, healthy vessels may not be readily available in the
proximity of the defect. A variety of options including a cross-leg free flap,
vein grafts, arteriovenous loops, and "bridging" flaps have been used to address
the issue. The purpose of this report is to present a case in which a 72-cm long
extended bilateral deep inferior epigastric artery perforator (DIEP) free flap
was used for coverage of a 20 * 25 cm soft tissue defect of the lower leg
following a Gustilo grade IIIC fracture in a 29-year-old man. Because usable
recipient vessels were far from the zone of injury, and to avoid complications
accompanying long vein grafts, a long flap was necessary. The exposed tibia
required coverage with a free flap, but peripheral portions of the defect with
exposed muscles could be covered with a skin graft. Thus, a 72 * 12 cm flap was
chosen. The flap was based on both bilateral DIEPs and on the superficial
circumflex iliac artery (SCIA). The flap survived completely with no
complications. After one debulking surgery, the flap and the donor site showed
pleasing cosmesis, and the patient could walk without crutches at 18 months after
the first surgery. In cases where no healthy recipient vessels can be found close
to the defect, we believe that the use of an extended bilateral DIEP flap may be
a feasible option which shortens or precludes vein grafts with no additional flap
donor sites.
PMID- 28703886
TI - Dual energy CT - a possible new method to assess regression of rectal cancers
after neoadjuvant treatment.
AB - BACKGROUND AND OBJECTIVES: The measurement of tumor regression after neoadjuvant
oncological treatment has gained increasing interest because it has a prognostic
value and because it may influence the method of treatment in rectal cancer. The
assessment of tumor regression remains difficult and inaccurate with existing
methods. Dual Energy Computed Tomography (DECT) enables qualitative tissue
differentiation by simultaneous scanning with different levels of energy. We
aimed to assess the feasibility of DECT in quantifying tumor response to
neoadjuvant therapy in loco-advanced rectal cancer. METHODS: We enrolled 11
patients with histological and MRI verified loco-advanced rectal adenocarcinoma
and followed up on them prospectively. All patients had one DECT scanning before
neoadjuvant treatment and one 12 weeks after using the spectral imaging scan
mode. DECT analyzing tools were used to determine the average quantitative
parameters; effective-Z, water- and iodine-concentration, Dual Energy Index
(DEI), and Dual Energy Ratio (DER). These parameters were compared to the
regression in the resection specimen as measured by the pathologist. RESULTS:
Changes in the quantitative parameters differed significantly after treatment in
comparison with pre-treatment, and the results were different in patients with
different CRT response rates. CONCLUSION: DECT might be helpful in the assessment
of rectal cancer regression grade after neoadjuvant treatment.
PMID- 28703887
TI - Recovery of precious metals from waste streams.
AB - As there is a high potential for microbe-based technologies to bring the recovery
of metals from waste streams to an ecologically friendly and financially
reasonable level, it is worth to invest efforts into the advancement of these
biotechnologies in the future.
PMID- 28703888
TI - Individual and partner's level of occupation and the association with HbA1c
levels in people with Type 2 diabetes mellitus: the Dutch Diabetes Pearl cohort.
AB - AIMS: Individual indicators of socio-economic status have been associated with
glycaemic control in people with Type 2 diabetes, but little is known about the
association between partner's socio-economic status and HbA1c levels. We
therefore examined the cross-sectional association between individual and
partner's level of occupation on HbA1c levels in people with Type 2 diabetes in
the Netherlands. METHODS: We included people with Type 2 diabetes with a partner
who were treated in primary, secondary and tertiary care in the Diabetes Pearl
cohort. Occupational level was classified according to International Standard
Classification of Occupations (ISCO)-08 skill levels. Linear regression analyses
were performed stratified for sex, and corrected for age, recruitment centre and
diabetes medication. RESULTS: In total, 3257 participants (59.8% men, mean 62.2+/
9.4 years) were included. For men, having a partner with an intermediate level of
occupation was associated with lower HbA1c levels [e.g. ISCO level 3: -2 mmol/mol
(95% CI -4;-1) or -0.2% (95% CI -0.4;-0.1)], compared with having a partner of
the highest occupational level (ISCO level 4). In women, having an unemployed
partner was associated with higher HbA1c levels [14 mmol/mol (95% CI 6; 22) or
1.3% (95% CI 0.6; 2.0)], compared with having a partner of the highest
occupational level. CONCLUSIONS: Partner's occupational status provided
additional information on the association between socio-economic status and HbA1c
levels in people with Type 2 diabetes. Women seemed to benefit from a partner
with a higher occupational status, while men seemed to benefit from a partner
with a lower status. Because of the cross-sectional nature of the present study,
more research is necessary to explore this association.
PMID- 28703889
TI - Implementation of a new blood cooler insert and tracking technology with
educational initiatives and its effect on reducing red blood cell wastage.
AB - BACKGROUND: The objective was to report a successful implementation of a blood
cooler insert and tracking technology with educational initiatives and its effect
on reducing red blood cell (RBC) wastage. STUDY DESIGN AND METHODS: The blood
bank database was used to quantify and categorize total RBC units issued in blood
coolers from January 2010 to December 2015 with and without the new inserts
throughout the hospital. Radiofrequency identification tags were used with
special software to monitor blood cooler tracking. An educational policy on how
to handle the coolers was initiated. Data were gathered from the software that
provided a real-time location monitoring of the blood coolers with inserts
throughout the institution. RESULTS: The implementation of the blood cooler with
inserts and tracking device reduced mean yearly RBC wastage by fourfold from
0.64% to 0.17% between 2010 and 2015. The conserved RBCs corresponded to a total
cost savings of $167,844 during the 3-year postimplementation period.
CONCLUSIONS: The implementation of new blood cooler inserts, tracking system, and
educational initiatives substantially reduced the mean annual total RBC wastage.
The cost to implement this initiative may be small if there is an existing
institutional infrastructure to monitor and track hospital equipment into which
the blood bank intervention can be adapted when compared to the cost of blood
wastage.
PMID- 28703890
TI - Targeted Therapies in Pancreatic Cancer: Promises and Failures.
AB - Pancreatic ductal adenocarcinoma (PDAC) is an incidence rate nearly equal to its
mortality rate. The poor prognosis of the disease can be explained by the absence
of effective biomarkers for screening and early detection, together with the
aggressive behavior and resistance to the currently available chemotherapy. The
therapeutic failure can also be attributed to the inter-/intra- tumor genetic
heterogeneity and the abundance of tumor stroma that occupies the majority of the
tumor mass. Gemcitabine is used in the treatment of PDAC, however, the response
rate is less than 12%. A recent phase III trial revealed that the combination of
oxaliplatin, irinotecan, fluorouracil, and leucovorin could be an option for the
treatment of metastatic PDAC patients with good performance status, although
these approaches can be resulted high toxicity level. Further investigations are
required to develop innovative anticancer agents that either improve gemcitabine
activity, within novel combinatorial approaches, or acts with a better efficacy
than gemcitabine. The aim of the current review is to give an overview about
preclinical andclinical studies targeting key dysregulated signaling pathways in
PDAC. This article is protected by copyright. All rights reserved.
PMID- 28703891
TI - Duration of action of mepivacaine and lidocaine in equine palmar digital
perineural blocks in an experimental lameness model.
AB - OBJECTIVE: To establish and compare the onset and duration of action of 2 local
anesthetics based on objective lameness and skin sensitivity assessment. STUDY
DESIGN: Interventional crossover experimental trial with balanced randomization.
ANIMALS: Eight horses. METHODS: Reversible forelimb lameness was induced in 8
horses. A palmar digital nerve block (PDNB) was applied with mepivacaine or
lidocaine (both 2%). Quantitative lameness and skin sensitivity data were
collected with an inertial sensor system and a force gauge, respectively. The
times to lameness resolution/skin desensitization (T1), consistent lameness
detection/partial return of skin sensitivity (T2), and complete return of
lameness/skin sensitivity (T3) were determined and compared between treatments
and assessment methods. RESULTS: Mepivacaine blocks resolved lameness in 8/8
horses, compared to 3/8 horses with lidocaine blocks. Both agents led to skin
desensitization in 8/8 horses. Skin desensitization occurred sooner than lameness
resolution after mepivacaine (P = .047). Duration of action was longer with
mepivacaine than lidocaine (mean T3_lameness mepivacaine 366 minutes, lidocaine
113 minutes (P = .038); T3_skin mepivacaine 195 minutes, lidocaine 63 minutes [P
<= .001]). Skin sensitivity returned sooner than lameness after lidocaine block
at T3 (P = .015). CONCLUSION: The use of lidocaine in PDNBs for the purpose of
lameness diagnosis should be reassessed, as it may not resolve lameness despite
loss of skin sensation. Mepivacaine is superior, with a reliable onset and longer
duration of action. Skin desensitization as an indicator for the onset of action
or effectiveness of PDNBs for mepivacaine and lidocaine, or as a measure of the
duration of action of lidocaine PDNBs should be interpreted with caution.
PMID- 28703892
TI - Disinfection of the peritoneal dialysis bag medication port: Comparison of
disinfectant agent and disinfection time.
AB - AIM: The aim of the present study was to compare different disinfection
techniques for the peritoneal dialysis bag medication port (MP). METHODS: An
experimental study was conducted testing different cleaning agents (70% alcohol
vs 2% chlorhexidine) and time periods (5, 10 and 60 s) for disinfection of the
MP. Five microorganisms (S. aureus, E. coli, A. baumannii and C. parapsilosis,
CNS) were prepared for use as contaminants of the MP. MP were incubated in
Tryptic soy broth at 36 degrees C for 24 h, after which, they were seeded on a
Biomerieux blood agar plate and incubated for 24 h at 36 degrees C. RESULTS:
Three hundred peritoneal dialysis bags were analyzed regarding the time expose to
the disinfectant showed a statistically significant difference in the number of
culture positive (7/100) P = 0.001; Gram positive (6/100) P = 0.006 for 5 s, one
positive culture and turbid bag with 10 s, while friction for 60 s showed all
negative results. The comparison between disinfectant, alcohol or chlorhexidine,
150 bag in each group, showed that the ones disinfected with alcohol had five
turbid bags, eight positive cultures and seven germs identified, while all bags
disinfected with chlorhexidine were negative for all parameters, with a
difference statistically significant (P = 0.004). CONCLUSION: Our results suggest
that the MP should be scrubbed with 2% chlorhexidine for at least 5 s; if alcohol
70% is used the length of friction should not be inferior to 10 s.
PMID- 28703893
TI - Molecular cloning and characterization of a short peptidoglycan recognition
protein from silkworm Bombyx mori.
AB - Peptidoglycan is the major bacterial component recognized by the insect immune
system. Peptidoglycan recognition proteins (PGRPs) are a family of pattern
recognition receptors that recognize peptidoglycans and modulate innate immune
responses. Some PGRPs retain N-acetylmuramoyl-L-alanine amidase (Enzyme
Commission number: 3.5.1.28) activity to hydrolyse bacterial peptidoglycans.
Others have lost the enzymatic activity and work only as immune receptors. They
are all important modulators for innate immunity. Here, we report the cloning and
functional analysis of PGRP-S4, a short-form PGRP from the domesticated silkworm,
Bombyx mori. The PGRP-S4 gene encodes a protein of 199 amino acids with a signal
peptide and a PGRP domain. PGRP-S4 was expressed in the fat body, haemocytes and
midgut. Its expression level was significantly induced by bacterial challenges in
the midgut. The recombinant PGRP-S4 bound bacteria and different peptidoglycans.
In addition, it inhibited bacterial growth and hydrolysed an Escherichia coli
peptidoglycan in the presence of Zn2+ . Scanning electron microscopy showed that
PGRP-S4 disrupted the bacterial cell surface. PGRP-S4 further increased
prophenoloxidase activation caused by peptidoglycans. Taken together, our data
suggest that B. mori PGRP-S4 has multiple functions in immunity.
PMID- 28703894
TI - Comparison of resting energy equations and total energy expenditure in
haemodialysis patients and body composition measured by multi-frequency
bioimpedance.
AB - BACKGROUND: Waste products of metabolism are retained in haemodialysis (HD)
patients. Cellular metabolism generates energy, and patients with greater energy
expenditure may therefore require more dialysis. To determine the amount of
dialysis required, equations estimating resting and total energy expenditure
(REE,TEE) are required. METHODS: We compared estimates of REE in HD patients
using established equations with a novel equation recently validated in HD
patients (HD equation). TEE was derived from REE (HD equation) and estimates of
physical activity obtained by questionnaire. REE and TEE relationships with
bioimpedance measured body composition were then determined. RESULTS: We studied
317 HD patients; 195 males (61.5%), 123 diabetic (38.9%), mean age 65.0 +/- 15.3
and weight 73.1 +/- 16.8 kg. REE from HD Equation was 1509 +/- 241 kcal/day,
which was greater than for Mifflin St Joer 1384 +/- 259, Harris-Benedict 1437 +/-
244, Katch-McArdle 1345 +/- 232 (all p < 0.05 vs HD Equation), but less than
Cunningham 1557 +/- 236 kcal/day. Bland Altman mean bias ranged from -263 to 55
kcal/day. TEE was 1727 (1558-1976) kcal/day, and on multi-variable analysis was
positively associated with skeletal muscle mass (beta 23.3, p < 0.001),
employment (beta 406.5, p < 0.001), low co-morbidity (beta 105.1, p = 0.006), and
protein nitrogen appearance (beta 2.7, p = 0.015), and negatively with age (beta
7.9, p < 0.001), and dialysis vintage (beta -121.2, p = 0.002). CONCLUSIONS: Most
standard equations underestimate REE in HD patients compared to the HD Equation.
TEE was greater in those with higher skeletal muscle mass and protein nitrogen
appearance, lower co-morbidity, age, and dialysis vintage, and the employed. More
metabolically active patients may require greater dialytic clearances.
PMID- 28703895
TI - HBV reactivation in patients with HCV/HBV cirrhosis on treatment with direct
acting antivirals.
AB - Anecdotal reports suggest that patients with chronic hepatitis C virus (HCV)
hepatitis and overt or occult hepatitis B virus (HBV) coinfection may reactivate
HBV when HCV is suppressed or cleared by direct-acting antivirals (DAAs). We
assessed the prevalence of overt or previous HBV coinfection and the risk of HBV
reactivation in patients with HCV cirrhosis treated with DAAs. This was a
retrospective cohort of 104 consecutive patients with HCV cirrhosis treated with
DAAs. Serum HCV-RNA and HBV-DNA were tested at weeks 4, 8 and 12 of DAAs therapy
and at week 12 of follow-up. At the start of DAAs, eight patients (7.7%) were
HBsAg positive/HBeAg negative with undetectable HBV-DNA and low levels of
quantitative HBsAg (four on nucleos(t)ide analogues [NUCs] and four inactive
carriers), 37 patients (35.6%) had markers of previous HBV infection (25 anti-HBc
positive, 12 anti-HBc/anti-HBs positive) and 59 (56.7%) had no evidence of HBV
infection. Sixty-seven patients (64.4%) were HCV-RNA negative at week 4 and 98
(94.2%) achieved sustained virological response. All four HBsAg-positive patients
treated with NUCs remained HBV-DNA negative, but three of four untreated patients
showed an increase in HBV-DNA of 2-3 log without a biochemical flare and achieved
HBV-DNA suppression when given NUCs. During or after DAAs, by conventional assay,
HBV-DNA remained not detectable in all 37 anti-HBc-positive patients but in three
of them (8.1%) HBV-DNA became detectable with a highly sensitive PCR. HBV
reactivation is likely to occur in untreated HBV/HCV-coinfected cirrhotic
patients when they undergo HCV treatment with DAAs. Pre-emptive therapy with NUCs
should be considered in this setting. Anti-HBc-positive patients rarely
reactivate HBV without clinical or virological outcomes.
PMID- 28703896
TI - Differential uptake of gold nanoparticles by 2 species of tadpole, the wood frog
(Lithobates sylvaticus) and the bullfrog (Lithobates catesbeianus).
AB - Engineered nanoparticles are aquatic contaminants of emerging concern that exert
ecotoxicological effects on a wide variety of organisms. We exposed
cetyltrimethylammonium bromide-capped spherical gold nanoparticles to wood frog
and bullfrog tadpoles with conspecifics and in combination with the other species
continuously for 21 d, then measured uptake and localization of gold. Wood frog
tadpoles alone and in combination with bullfrog tadpoles took up significantly
more gold than bullfrogs. Bullfrog tadpoles in combination with wood frogs took
up significantly more gold than controls. The rank order of weight-normalized
gold uptake was wood frogs in combination > wood frogs alone > bullfrogs in
combination > bullfrogs alone > controls. In all gold-exposed groups of tadpoles,
gold was concentrated in the anterior region compared with the posterior region
of the body. The concentration of gold nanoparticles in the anterior region of
wood frogs both alone and in combination with bullfrogs was significantly higher
than the corresponding posterior regions. We also measured depuration time of
gold in wood frogs. After 21 d in a solution of gold nanoparticles, tadpoles lost
>83% of internalized gold when placed in gold-free water for 5 d. After 10 d in
gold-free water, tadpoles lost 94% of their gold. After 15 d, gold concentrations
were below the level of detection. Our finding of differential uptake between
closely related species living in similar habitats with overlapping geographical
distributions argues against generalizing toxicological effects of nanoparticles
for a large group of organisms based on measurements in only one species. Environ
Toxicol Chem 2017;36:3351-3358. (c) 2017 SETAC.
PMID- 28703897
TI - Media Representations of Breech Birth: A Prospective Analysis of Web-Based News
Reports.
AB - INTRODUCTION: Recent research has demonstrated that the media presentation of
childbirth is highly medicalized, often portraying birth as risky and dramatic.
Media representation of breech presentation and birth is unexplored in this
context. This study aimed to explore the content and tone of news media reports
relating to breech presentation and breech birth. METHODS: Google alerts were
created using the terms breech and breech birth in online English-language news
sites over a 3-year period from January 1, 2013, to December 31, 2015. Alerts
were received daily and filed for analysis, and data were analyzed to generate
themes. RESULTS: A total of 138 web-based news reports were gathered from 9
countries. Five themes that arose from the data included the problem of breech
presentation, the high drama of vaginal breech birth, the safe option of cesarean
birth versus dangers of vaginal breech birth, the defiant mother versus the
saintly mother, and vaginal breech birth and medical misadventure. DISCUSSION:
Media reports in this study predominantly demonstrated negative views toward
breech presentation and vaginal breech birth. Cesarean birth was portrayed as the
safe option for breech birth, while vaginal breech birth was associated with poor
outcomes. Media presentations may impact decision making about mode of birth for
pregnant women with a breech fetus. Health care providers can play an important
role in balancing the media depiction of planned vaginal breech birth by
providing nonjudgmental, evidence-based information to such women to facilitate
informed decision making for birth.
PMID- 28703898
TI - Long-term outcomes of tonsillectomy for IgA nephropathy patients: A retrospective
cohort study, two-centre analysis with the inverse probability therapy weighting
method.
AB - AIM: The effect of tonsillectomy on IgA nephropathy remains controversial. The
aim of this study was to compare the effect of tonsillectomy on the outcome, end
stage kidney disease (ESKD) and all-cause death in IgA nephropathy patients who
did and did not undergo tonsillectomy. METHODS: All basic data were
retrospectively gathered from patients who had undergone renal biopsies at two
Japanese clinical centres. Two hundred and twenty-seven patients were eligible
for the study, with a median age of 34 (Interquartile range (IQR): 25-43) years
and median follow-up of 92 (IQR: 40-178) months. The primary endpoint was the
composite outcome of the onset of ESKD and all-cause death before ESKD. We
performed a Cox proportional hazard regression analysis after adjusting for
patient characteristics using the inverse probability therapy weighting (IPTW)
method and a Cox analysis using the Matching method. Similarly, we analyzed these
outcomes in a mild cohort. RESULTS: We were unable to find any significant
advantages of tonsillectomy in either analysis (IPTW and matching, HR: 0.40 (0.12
1.36) P = 0.072 and 0.78 (0.13-4.64) P = 0.786). However, in the mild cohort
analysis, our data showed that the Tonsillectomy group tended to be less likely
to reach the composite outcomes than the Not Tonsillectomy group with statistical
significance (hazard ratio (HR), <0.001 [CI <0.001 to <0.001, P = 0.039]).
CONCLUSION: In this study, our findings led us to conclude that performing
tonsillectomy in an early and timely manner may have predisposition of less poor
prognosis.
PMID- 28703899
TI - Coronary artery calcification score and common iliac artery calcification score
in non-dialysis CKD patients.
AB - AIM: Many studies have validated Agatston's coronary artery calcification score
(CACS) for assessing vascular calcification (VC) in chronic kidney disease (CKD)
patients. This study aimed to evaluate the CACS and common iliac artery
calcification score (IACS) and to examine the variables related to each score.
METHODS: The subjects were 145 non-dialysis CKD patients. The CACS and IACS were
determined using the same thoracicoabdominal multi-detector computed tomography.
Multiple regression analyses were performed to assess the factors associated with
the CACS or IACS. The associations between progression to renal replacement
therapy (RRT) and the CACS or IACS were studied using Cox hazards models.
RESULTS: The subjects' median age, estimated glomerular filtration rate (eGFR),
and follow-up period were 72 (62-78) years, 32 (18-50) mL/min/1.73m2 , and 864
(550-1425) days, respectively. Age, diabetes, the serum phosphate level, and the
eGFR were found to be significant factors of the CACS [beta (95% CI): 0.38 (0.02
0.04), P < 0.0001, 0.28 (0.19-0.50), P < 0.0001, 0.16 (0.03-0.45), P < 0.05 and
0.15 (-0.02-0.00), P < 0.05, respectively]. Age and diabetes were shown to be
significant factors of the IACS [beta (95% CI): 0.53 (0.04-0.06), P < 0.0001, and
0.18 (0.07-0.40), P < 0.01, respectively]. Progression to RRT occurred in 31
patients and was significantly associated with the CACS (hazard ratio: 1.01, P <
0.01), urinary protein level and eGFR, but not the IACS. CONCLUSION: Chronic
kidney disease related risk factors for VC, such as the eGFR and
hyperphosphataemia, are significantly associated with a high CACS, but not a high
IACS, and the CACS is a significant predictor of progression to RRT.
PMID- 28703900
TI - Rapid genetic counseling and testing in newly diagnosed breast cancer: Patients'
and health professionals' attitudes, experiences, and evaluation of effects on
treatment decision making.
AB - BACKGROUND: Rapid genetic counseling and testing (RGCT) in newly diagnosed high
risk breast cancer (BC) patients may influence surgical treatment decisions. To
successfully integrate RGCT in practice, knowledge of professionals', and
patients' attitudes toward RGCT is essential. METHODS: Between 2008 and 2010, we
performed a randomized clinical trial evaluating the impact of RGCT. Attitudes
toward and experience with RGCT were assessed in 265 patients (at diagnosis, 6-
and 12-month follow-up) and 29 medical professionals (before and after the
recruitment period). RESULTS: At 6-month follow-up, more patients who had been
offered RGCT felt they had been actively involved in treatment decision-making
than patients who had been offered usual care (67% vs 48%, P = 0.06). Patients
who received DNA-test results before primary surgery reported more often that
RGCT influenced treatment decisions than those who received results afterwards (P
< 0.01). Eighty-seven percent felt that genetic counseling and testing (GCT)
should preferably take place between diagnosis and surgery. Most professionals
(72%) agreed that RGCT should be routinely offered to eligible patients. Most
patients (74%) and professionals (85%) considered surgeons the most appropriate
source for referral. CONCLUSIONS: RGCT is viewed as helpful for newly diagnosed
high-risk BC patients in choosing their primary surgery and should be offered
routinely by surgeons.
PMID- 28703901
TI - Treatment of post-caesarean niche: the accumulation of evidence.
PMID- 28703902
TI - Prevalence and characteristics of paediatric Type 2 diabetes in the Republic of
Ireland.
AB - OBJECTIVE: To establish the prevalence of paediatric Type 2 diabetes in the
Republic of Ireland and describe patient demographics, initial presentation,
management, outcomes, comorbidities and complications. METHODS: Using a
standardized proforma we conducted a cross-sectional survey of children and
adolescents aged < 16 years with a diagnosis of Type 2 diabetes between October
and December 2015 in each of the 19 centres in the Republic of Ireland
responsible for the care of children with diabetes. RESULTS: Twelve cases of Type
2 diabetes were identified, giving a prevalence in children aged <16 years of
1.2/100 000 (95% CI 0.6 to 2). Six of these children (50%) were white, two (33%)
of whom were members of the travelling community. Four (33%) were of black
ethnicity. The prevalence of Type 2 diabetes in traveller children was 16.1/100
000 (95% CI 1.9 to 58.1) and was similar to that in black children, a known high
risk group, which was 13.3/100 000 (95% CI 3.6 to 34.1). The median current HbA1c
value was 51 mmol/mol (6.8%) and four (33%) of the children achieved the
International Society for Pediatric and Adolescent Diabetes target HbA1c of <=48
mmol/mol (6.5%). Seven (59%) children were managed on metformin monotherapy,
three (25%) were managed on insulin and metformin in combination, and two (16%)
were receiving dietary management. CONCLUSION: This was the first national study
to estimate the prevalence of childhood Type 2 diabetes in Ireland. Despite their
white ethnicity, traveller children appear to be a high-risk group, but this
finding requires further study.
PMID- 28703903
TI - Dosage Optimization of Nemolizumab Using Population Pharmacokinetic and
Pharmacokinetic-Pharmacodynamic Modeling and Simulation.
AB - Nemolizumab is a humanized anti-interleukin-31 receptor A monoclonal antibody for
treating atopic dermatitis, and it especially improves pruritus. The objective of
the simulation study was to optimize the dose regimen using a flat dose. The
serum nemolizumab concentration and pruritus visual analog scale as an efficacy
end point were modeled using the population analysis approach in 299 patients
with atopic dermatitis who received placebo or doses between 0.1 and 3 mg/kg as a
single dose once every 4 weeks or 2 mg/kg once every 8 weeks. A 1-compartment
model with first-order absorption was employed as the pharmacokinetic model. An
indirect turnover model with an inhibition component was employed as the main
part of the pharmacokinetic-pharmacodynamic model. The models well described the
observations. Therefore, simulations with several dose regimens were performed to
optimize the dose regimen including a flat dose. The simulated area under the
concentration-time curve at a steady state around 75 mg in the every-4-week
regimen corresponds to that associated with the dose range of 0.5 to 2 mg/kg in
the 4-week regimen. The simulated pruritus visual analog scale also showed a
similar tendency. These simulation results support dose optimization during the
clinical development program of nemolizumab.
PMID- 28703904
TI - Updates From the Literature, July/August 2017.
PMID- 28703905
TI - Successful treatment of chronic hepatitis C infection with directly acting
antivirals in renal transplant recipients.
AB - AIMS: The data regarding the treatment of chronic hepatitis C (CHC) in renal
transplant recipients is lacking from the Asia-Pacific region. The aim of the
present study was to assess the safety and efficacy of directly acting antivirals
(DAAs) in the treatment of CHC infection in renal transplant recipients. METHODS:
A total of 47 CHC infected renal transplant recipients were enrolled in this real
life observational cohort analysis between March 2015 and September 2016.
Presence of hepatic fibrosis/cirrhosis was assessed on transient elastography
(Fibroscan). Fourteen patients were treated with Sofosbuvir and Ribavirin for 24
weeks. Twenty-two patients received Sofosbuvir and Ledipasvir and 12 patients
received Sofosbuvir and Daclatasvir with (n = 3) or without (n = 31) Ribavirin
for 12 or 24 weeks depending on genotype and underlying cirrhosis. Data were
analyzed for safety and treatment efficacy [sustained virological response at 12
weeks (SVR12)]. RESULTS: The median baseline HCV RNA concentration in the whole
group was 7.38 * 106 IU/mL (1.23 * 104 -6.36 * 107 ). The SVR12 rates were 100%
in all groups except in the Sofosbuvir and Ribavirin group (86%). Transient
Elastography revealed minimal or no fibrosis (F0-F1) in 31 (65.96%) patients,
moderate fibrosis (F2) in 11 (23.4%) patients and cirrhosis in five (10.64%)
patients. The only serious adverse effect was anaemia observed in eight (57%)
patients in the Sofosbuvir and Ribavirin group. CONCLUSION: DAAs including
Sofosbuvir, Daclatasvir and Ledipasvir with or without ribavirin are safe and
effective for the treatment of chronic hepatitis C in renal transplant
recipients.
PMID- 28703906
TI - Reply to: Over-REACHing Conclusions.
PMID- 28703908
TI - Over-REACHing Conclusions.
PMID- 28703907
TI - TGF-beta1-induced CK17 enhances cancer stem cell-like properties rather than EMT
in promoting cervical cancer metastasis via the ERK1/2-MZF1 signaling pathway.
AB - Tumor metastasis remains a major obstacle for improving overall cancer survival
in cervical cancer (CC), which may be due to the existence of tumor
microenvironment-related cancer stem cells (CSCs) and epithelial-mesenchymal
transition (EMT). The mechanism underlying these processes needs to be further
elucidated. Here, we report that TGF-beta1, one of the key microenvironmental
stimuli, can enhance CSC characteristics, facilitate the EMT, and induce CK17.
Silencing CK17 expression attenuated CSC-like properties without affecting the
EMT markers induced by TGF-beta1, whereas forced overexpression of CK17 promoted
lymphatic metastasis in vivo even without EMT inducement. Inhibitors of ERK1/2
signaling drastically decreased the induction of CK17 mediated by TGF-beta1. By
combined computational and experimental approaches, we identified and validated
that MZF1 was a key transcription factor binding to the promoter of CK17. Taken
together, these results demonstrate that CK17 induced by the TGF-beta1-ERK1/2
MZF1 signaling pathway facilitates metastasis by promoting the acquisition of CSC
properties rather than by inducing the EMT process in CC, suggesting that this
CK17-related signaling pathway might be a suitable target for the development of
therapy for CC metastasis.
PMID- 28703909
TI - Examination of the Pharmacology of Oxytocin and Clinical Guidelines for Use in
Labor.
AB - The use of exogenous oxytocin to induce or augment labor has increased in recent
years. This literature-informed review examines the action of this medication and
the potential associated complications, with an evaluation of current
professional practice guidelines. A brief history of the use of exogenous
oxytocin for labor induction or augmentation is presented. In addition, risk
management strategies for the prevention of oxytocin-related adverse outcomes and
subsequent litigation are identified.
PMID- 28703910
TI - Medialis pedis flap for reconstruction of weight bearing heel.
AB - BACKGROUND: Among the various flaps available for the reconstruction of the heel,
a medial plantar flap has been widely accepted as the most ideal. This flap,
however, involves the medial plantar nerve and its cutaneous branches, which may
lead to postoperative hyperesthesia and dual sensation. The purpose of this
report was to report the outcomes of the use of the medialis pedis flap for the
coverage of weight bearing heel soft tissue defect. PATIENTS AND METHODS: A total
of 8 patients who had undergone reconstruction of the weight bearing heel with
the medialis pedis flap were enrolled for this study. There were 6 male and 2
female patients and the mean age was 46 years. The causes of the defects included
pressure sore, crushing injury and malignant melanoma. The mean size of the
defects was 3 * 4 cm. Five cases were reconstructed with island flaps and 3 were
covered with free flaps. RESULTS: The mean size of the flaps was 3*5 cm. All
flaps survived. One case developed arterial insufficiency and was treated with a
vein graft. Ambulation in normal shoes was possible in all the patients. Seven
cases did not report pain, but 1 case complained of mild pain. No case reported
complications including pain at the donor site, ulcerations, sensory loss,
hyperesthesia, or sensory disturbance. The mean follow-up period was 14.4 months.
CONCLUSIONS: The medialis pedis flap may be considered a useful flap for the
reconstruction of soft tissue defects smaller than 5 cm in the weight bearing
heel.
PMID- 28703911
TI - Low incidence of metastasis and recurrence from cutaneous squamous cell carcinoma
found in a UK population: Do we need to adjust our thinking on this rare but
potentially fatal event?
AB - BACKGROUND AND METHODS: Cutaneous squamous cell carcinoma (cSCC) is the commonest
skin cancer with metastatic potential, however, reported rates of metastasis
varies greatly. All cases of primary cSCC on the Isle of Wight between 2005 and
2014 were identified and retrospectively followed for recurrence and/or
metastasis. Primary outcome was to identify the rate of metastasis/recurrence
from cSCC. Secondary outcomes included associated risk factors for
metastasis/recurrence, death from cSCC, and time from diagnosis of primary cSCC
to event. RESULTS: A total of 1122 patients with 1495 tumors were identified
within the study period. A total of 18 metastasized and 40 recurred, an overall
incidence of 1.2% and 2.7%, respectively. Eight patients died from their disease.
CONCLUSIONS: Risk of metastasis from cSCC in the UK general population is likely
to be in the order of 1.2%. Where metastasis occurs this is often within 2 years.
Recurrence rates are higher following curette and cautery. DISCUSSION: If treated
adequately both recurrence and metastasis from cSCC is a rare event. Not all cSCC
cases need follow-up instead time should be spent educating patients around signs
of recurrence/metastasis then discharged, relieving burden on secondary care.
Multi-disciplinary teaming meetings are expensive and should be limited to
complex cases.
PMID- 28703912
TI - Resilience: Bouncing Back from Hard Times.
PMID- 28703913
TI - Ascaris suum infection modulates inflammation: Implication of CD4+ CD25high
Foxp3+ T cells and IL-10.
AB - Helminth infections have the ability to modulate host's immune response through
mechanisms that allow the chronic persistence of the worms in the host. Here, we
investigated the mechanisms involved on the suppressive effect of Ascaris suum
infection using a murine experimental model of LPS-induced inflammation. We found
that infection with A. suum markedly inhibited leucocyte influx induced by LPS
into air pouches, suppressed secretion of pro-inflammatory cytokines (IL-1beta,
TNF-alpha and IL-6) and induced high levels of IL-10 and TGF-beta. Augmented
frequency of CD4+ CD25high Foxp3+ T cells was observed in the mesenteric lymph
nodes of infected mice. Adoptive transfer of purified CD4+ CD25+ T cells to
recipient uninfected mice demonstrated that these cells were able to induce a
suppressive effect in the LPS-induced inflammation in air pouch model. In
addition, adoptive transfer of CD4+ CD25+ T cells derived from IL-10 knockout
mice suggests that this suppressive effect of A. suum infection involves IL-10
cytokine. In conclusion, our results demonstrated that A. suum experimental
infection was capable of suppressing LPS-induced inflammation by mechanisms,
which seem to be dependent on responses of CD4+ CD25+ T cells and secretion of IL
10 cytokine.
PMID- 28703914
TI - Hsd3b2 associated in modulating steroid hormone synthesis pathway regulates the
differentiation of chicken embryonic stem cells into spermatogonial stem cells.
AB - Steroid hormones regulate differentiation of various types of cell during
embryogenesis. Testosterone is one of the androgens that bind to receptors to
regulate gene expression and promote spermatogenesis. Our results showed that
testosterone, as a product of steroid hormones synthesis pathway, could
facilitate the differentiation of embryonic stem cells (ESCs) into spermatogonial
stem cells (SSCs). The analysis of the steroid hormones synthesis pathway
demonstrated that 3beta-hydroxysteroid dehydrogenase2 (Hsd3b2) plays a major role
in the synthesis of testosterone. In the absence of Hsd3b2, the expression of
downstream genes such as Cyp1a1, Ugt1a1, and Hsd17b7 was not maintained. This
reduction is probably due to the down-regulation of the steroid hormones
synthesis pathway. Furthermore, qRT-PCR, immunofluorescence, and flow cytometry
analysis confirmed that the steroid hormones synthesis pathway could facilitate
the differentiation of ESCs. Altogether, these results lead to a model in which
Hsd3b2 regulates ESCs differentiation via modulating the activity of steroid
hormones synthesis pathway.
PMID- 28703915
TI - Self-Normalized Detection of ANXA3 from Untreated Urine of Prostate Cancer
Patients without Digital Rectal Examination.
AB - A noninvasive quantitative assay that is capable of identifying prostate cancer
biomarkers in untreated urine is an attractive diagnosis tool, but this method is
subject to various obstacles. Difficulties presented by untreated urine include
varying salt concentrations, and pH levels that may be different even though they
are from the same patient. Untreated urine also presents interference from other
biomolecules and possesses a fewer number of cancer biomarkers than can be found
in serum. As a result, urine preconditioning processes and digital rectal
examination (DRE) to increase biomarker secretion are mandatory in current urine
assays. To address these challenges, an ion-responsive urine sensor (IRUS) that
measures differential electrical signals is proposed as a self-normalized
detection method. The proposed IRUS is based on a FET biosensor with a disposable
sensing gate and has the capability to detect the prostate cancer antigen ANXA3
in untreated patient urine. The IRUS can detect ANXA3 at <1 fg mL-1 with high
reliability. In addition, it is found that ANXA3 levels in urine show clinically
significant correlation with real tumor volumes. This paper provides a guideline
in developing a clinically ready accurate noninvasive platform, which is capable
of predicting prostate cancer using untreated urine without DRE.
PMID- 28703916
TI - Down-regulation of microRNA let-7d inhibits the proliferation and invasion of
trophoblast cells in preeclampsia.
AB - Preeclampsia (PE) is a serious pregnancy complication that continues to adverse
effects on mother and the fetus. The study investigated the effect of microRNA
let-7d (miR-let-7d) on the proliferation and invasion of trophoblast cells (TC)
in PE. In situ hybridization techniques were employed to evaluate the miR-let-7d
expressions in the placental tissues from 63 PE patients as well as 65 normal
placental tissues. Transfection of pre-let-7d, anti-let-7d, and their
corresponding control sequences was performed in TCs obtained from PE. The blank
group was composed of TCs no transfection and normal group consisted of normal
TCs. Expressions of proliferation and invasion markers in TCs were detected by
qRT-PCR. Proliferation, apoptosis, and the invasion ability of the TCs were
determined using a CCK-8 assay, flow cytometry, and Transwell assay. In
comparison to the normal placental tissues, PE placental tissues exhibited
increased levels of let-7d expression. Following transfection of anti-let-7d,
when compared with the blank group, the anti-let-7d group displayed increased
levels of proliferation ability, expression of proliferation labeling proteins
PCNA and Ki67, number of TCs as well as expressions of the invasion related
proteins MMP-2, MMP-9, and TIMP-1. In contrast declines in cell apoptosis rate
were observed. Compared with the blank group, the changes of the indexes were
reversed in the pre-let-7d group. The study provided evidence suggesting that low
expression levels of miR-let-7d plays a central role in suppressing apoptosis in
addition to promoting the proliferation and invasion of PE TCs.
PMID- 28703917
TI - The beauty of bile.
PMID- 28703918
TI - Association between the vitamin D receptor gene polymorphisms and diabetic
nephropathy risk: A meta-analysis.
AB - AIMS: Diabetic nephropathy (DN) is a severe microvascular complication frequently
associated with type 1 and type 2 diabetes mellitus. The objective of this study
was to estimate the effect between Apa I, Bsm I, Fok I and Taq I polymorphisms of
the vitamin D receptor (VDR) gene and DN susceptibility. METHODS: Eligible case
control studies published updated to March 2017 were searched. The odds ratio
(OR) and 95% confident intervals (CI) were used to calculate the strength of
effect. RESULTS: Twelve articles were finally screened out, including 3954
diabetic patients and 1248 healthy controls. When compared with the diabetic
patients without nephropathy, our results found that only the Bsm I polymorphism
was associated with increased risk of DN under the allelic model (B vs. b: OR =
1.51, 95% CI = 1.03-2.20, P = 0.04) and dominant model (BB + Bb vs. bb: OR =
1.52, 95% CI = 1.00-2.31, P = 0.05). When compared with the healthy controls, our
results showed that the Bsm I polymorphism was associated with the DN
susceptibility under the allelic model (B vs. b: OR = 1.80, 95% CI = 1.12-2.91, P
= 0.02), the homogeneous model (BB vs. bb: OR = 1.43, 95% CI = 1.03-1.98, P =
0.03), and the domain model (BB + Bb vs. bb: OR = 1.80, 95% CI = 1.06-3.05, P =
0.03); the Taq I variant was associated with increased risk of DN only under the
heterogeneous model (Tt vs. tt: OR = 2.29, 95% CI = 1.04-5.03, P = 0.04).
CONCLUSION: Our results suggested that B allele, and BB + Bb genotypes of Bsm I
variant, Tt genotype of Taq I variant might be risk factors for DN. Future
researches are still needed to identify our results.
PMID- 28703919
TI - Cingulate and cerebellar beta oscillations are engaged in the acquisition of
auditory-motor sequences.
AB - Singing, music performance, and speech rely on the retrieval of complex sounds,
which are generated by the corresponding actions and are organized into
sequences. It is crucial in these forms of behavior that the serial organization
(i.e., order) of both the actions and associated sounds be monitored and learned.
To investigate the neural processes involved in the monitoring of serial order
during the initial learning of sensorimotor sequences, we performed
magnetoencephalographic recordings while participants explicitly learned short
piano sequences under the effect of occasional alterations of auditory feedback
(AAF). The main result was a prominent and selective modulation of beta (13-30
Hz) oscillations in cingulate and cerebellar regions during the processing of AAF
that simulated serial order errors. Furthermore, the AAF-induced modulation of
beta oscillations was associated with higher error rates, reflecting compensatory
changes in sequence planning. This suggests that cingulate and cerebellar beta
oscillations play a role in tracking serial order during initial sensorimotor
learning and in updating the mapping of the sensorimotor representations. The
findings support the notion that the modulation of beta oscillations is a
candidate mechanism for the integration of sequential motor and auditory
information during an early stage of skill acquisition in music performance. This
has potential implications for singing and speech. Hum Brain Mapp 38:5161-5179,
2017. (c) 2017 Wiley Periodicals, Inc.
PMID- 28703920
TI - Neutrophil-specific antigens, immunobiology, and implications in transfusion
medicine and blood disorders.
PMID- 28703921
TI - Estimating and modelling the transmissibility of Middle East Respiratory Syndrome
CoronaVirus during the 2015 outbreak in the Republic of Korea.
AB - BACKGROUND: Emerging respiratory infections represent a significant public health
threat. Because of their novelty, there are limited measures available to control
their early spread. Learning from past outbreaks is important for future
preparation. The Middle Eastern Respiratory Syndrome CoronaVirus (MERS-CoV ) 2015
outbreak in the Republic of Korea (ROK) provides one such opportunity.
OBJECTIVES: We demonstrated through quantitative methodologies how to estimate
MERS-CoV's transmissibility and identified the effective countermeasures that
stopped its spread. METHODS: Using the outbreak data, statistical methods were
employed to estimate the basic reproductive number R0 , the average number of
secondary cases produced by a typical primary case during its entire infectious
period in a fully susceptible population. A transmission dynamics model was also
proposed to estimate R0 and to identify the most effective countermeasures. The
consistency between results will provide cross-validation of the approaches.
RESULTS: R0 ranged from 2.5 with 95% confidence interval (CI): [1.7, 3.1] (using
the sequential Bayesian method) to 7.2 with 95% CI: [5.3, 9.4] (using the
Nowcasting method). Estimates from transmission model were higher but overlapped
with these. Personal protection and rapid confirmation of cases were identified
as the most important countermeasures. CONCLUSIONS: Our estimates were in
agreement with others from the ROK outbreak, albeit significantly higher than
estimates based on other small outbreaks and sporadic cases of MERS-CoV. The
large-scale outbreak in the ROK was jointly due to the high transmissibility in
the healthcare-associated setting and the Korean culture-associated contact
behaviour. Limiting such behaviour by rapidly identifying and isolating cases and
avoiding high-risk contacts effectively stopped further transmission.
PMID- 28703922
TI - Sensitivity evaluation and selective plane imaging geometry for x-ray-induced
luminescence imaging.
AB - PURPOSE: X-ray-induced luminescence (XIL) is a hybrid x-ray/optical imaging
modality that employs nanophosphors that luminescence in response to x-ray
irradiation. X-ray-activated phosphorescent nanoparticles have potential
applications in radiation therapy as theranostics, nanodosimeters, or
radiosensitizers. Extracting clinically relevant information from the luminescent
signal requires the development of a robust imaging model that can determine
nanophosphor distributions at depth in an optically scattering environment from
surface radiance measurements. The applications of XIL in radiotherapy will be
limited by the dose-dependent sensitivity at depth in tissue. We propose a novel
geometry called selective plane XIL (SPXIL), and apply it to experimental
measurements in optical gel phantoms and sensitivity simulations. METHODS: An
imaging model is presented based on the selective plane geometry which can
determine the detected diffuse optical signal for a given x-ray dose and
nanophosphor distribution at depth in a semi-infinite, optically homogenous
material. The surface radiance in the model is calculated using an analytical
solution to the extrapolated boundary condition. Y2 O3 :Eu3+ nanoparticles are
synthesized and inserted into various optical phantom in order to measure the
luminescent output per unit dose for a given concentration of nanophosphors and
calibrate an imaging model for XIL sensitivity simulations. SPXIL imaging with a
dual-source optical gel phantom is performed, and an iterative Richardson-Lucy
deconvolution using a shifted Poisson noise model is applied to the measurements
in order to reconstruct the nanophosphor distribution. RESULTS: Nanophosphor
characterizations showed a peak emission at 611 nm, a linear luminescent response
to tube current and nanoparticle concentration, and a quadratic luminescent
response to tube voltage. The luminescent efficiency calculation accomplished
with calibrated bioluminescence mouse phantoms determines 1.06 photons were
emitted per keV of x-ray radiation absorbed per g/mL of nanophosphor
concentration. Sensitivity simulations determined that XIL could detect a
concentration of 1 mg/mL of nanophosphors with a dose of 1 cGy at a depth ranging
from 2 to 4 cm, depending on the optical parameters of the homogeneous diffuse
optical environment. The deconvolution applied to the SPXIL measurements could
resolve two sources 1 cm apart up to a depth of 1.75 cm in the diffuse phantom.
CONCLUSIONS: We present a novel imaging geometry for XIL in a homogenous, diffuse
optical environment. Basic characterization of Y2 O3 :Eu3+ nanophosphors are
presented along with XIL/SPXIL measurements in optical gel phantoms. The diffuse
optical imaging model is validated using these measurements and then calibrated
in order to execute initial sensitivity simulations for the dose-depth
limitations of XIL imaging. The SPXIL imaging model is used to perform a
deconvolution on a dual-source phantom, which successfully reconstructs the
nanophosphor distributions.
PMID- 28703924
TI - Chronic kidney disease in Australian HIV-infected patients: analysis of the
Australian HIV Observational Database.
AB - AIM: To examine data from the Australian HIV Observational Database (AHOD) to,
firstly, describe the incidence of chronic kidney disease (CKD) and rate of loss
of renal function in HIV-infected individuals living in Australia, and then to
examine the risk factors contributing to CKD in this population. METHODS: AHOD
patients over 18 years of age were eligible if they had at least two serum
creatinine measurements from 1 April 2008 until 31 March 2016 and an initial
estimated glomerular filtration rate (eGFR) greater than 60 mL/min/1.73 m3 . Cox
proportional hazards models were used to assess risk factors for CKD, which
included key patient demographic data and antiretroviral therapy (ART) exposure.
RESULTS: Of 1924 patients included in the analysis between April 2008 and March
2016, 81 (4.2%) developed CKD (confirmed eGFR of less than 60 mL/min/1.73 m3
through two consecutive eGFR measurements at least three months apart). Of the
examined risk factors, baseline age, baseline eGFR, and the route of HIV
acquisition were statistically significant predictors of development of CKD. ART
exposure, viral hepatitis co-infection, high viral load and low CD4 lymphocyte
count were not found to be significant risk factors for CKD. CONCLUSION: This is
the first study to investigate the risk factors for development of CKD amongst
Australian HIV-infected patients using cohort data. It highlights the need for
awareness of renal risk factors, particularly amongst older patients or in those
with pre-existing renal dysfunction. Further research is required to explore the
discrepancy between patients who have acquired HIV through different means of
exposure.
PMID- 28703923
TI - Autophagy in neurodegenerative diseases: pathogenesis and therapy.
AB - The most prevalent pathological features of many neurodegenerative diseases are
the aggregation of misfolded proteins and the loss of certain neuronal
populations. Autophagy, as major intracellular machinery for degrading aggregated
proteins and damaged organelles, has been reported to be involved in the
occurrence of pathological changes in many neurodegenerative disorders, including
Alzheimer's disease, Parkinson's disease, Huntington's disease and amyotrophic
lateral sclerosis. In this review, we summarize most recent research progress in
this topic and provide a new perspective regarding autophagy regulation on the
pathogenesis of neurodegenerative diseases. Finally, we discuss the signaling
molecules in autophagy-related pathways as therapeutic targets for the treatment
of these diseases.
PMID- 28703925
TI - Role of Prophylactic Oxytocin in the Third Stage of Labor: Physiologic Versus
Pharmacologically Influenced Labor and Birth.
AB - INTRODUCTION: Maternity care providers administer oxytocin prophylactically to
prevent postpartum hemorrhage (PPH). Prophylactic oxytocin is generally
considered effective and safe and is promoted by national organizations for
standardized use. In this article, the evidence supporting prophylactic oxytocin
administration for women undergoing spontaneous labor and birth compared with
women whose labors included administration of exogenous oxytocin for induction or
augmentation is explored. METHODS: Using data from randomized controlled trials
included in 2 recent Cochrane meta-analyses papers, only studies with women in
spontaneous labor were selected for inclusion (N = 4 studies). Outcomes of
immediate postpartum bleeding volumes (>= 500 mL or 1000 mL), risk for blood
transfusion, and risk for administration of more uterotonic medication were
pooled from these 4 studies. Focused random effects meta-analytics were used.
RESULTS: Compared to women without prophylactic oxytocin, women who received
prophylactic oxytocin had a lower risk of having a 500 mL or higher blood loss.
However, prophylactic oxytocin did not lower risk of PPH (>= 1000 mL), blood
transfusion, or need for additional uterotonic treatment. DISCUSSION:
Prophylactic oxytocin may not confer the same benefits to women undergoing
spontaneous labor and birth compared to women laboring with oxytocin infusion.
Reasons for this difference are explored from a pharmacologic perspective. In
addition, the value of prophylactic oxytocin given recent changes in the
definition of PPH from greater than or equal to 500 mL to 1000 mL or more after
birth is discussed. Finally, gaps in research on adverse effects of prophylactic
oxytocin are presented. More research is needed on reducing risk of PPH for women
in spontaneous labor.
PMID- 28703926
TI - Difficult conversations: adults with diabetes and the discussion of microvascular
complications.
AB - AIMS: To investigate the experiences among adults with diabetes of discussions of
microvascular complications and provide recommendations for providers. METHODS:
We performed a qualitative study in 148 adults with Type 1 and Type 2 diabetes
(56% women, 95% white, mean age 60+/-13 years, 65% with Type 1 diabetes, 71% with
>=1 microvascular complication). Data were analysed using content analysis.
RESULTS: At their first discussion of microvascular complications, 93% of
participants (138/148) recalled providers using a preventative approach including
clinical suggestions, factual information and warnings. At complication
diagnosis, 78% of participants (82/105) perceived provider support through
comprehensive interactive education, specific self-care guidance, reassuring
messages, and referrals and follow-ups. In response to complication diagnosis,
48% (50/105) felt scared, 46% (48/105) had 'a wake-up call', and 86% (90/105)
reported increasing >=1 specific area of self-care. Participants recommended
providers offer factual and complete information, specific self-care guidance,
and positive honesty, with an individualized and collaborative approach that
includes psychosocial assessment and referrals and lacks 'scare tactics' and
blame. CONCLUSIONS: Adults with diabetes want to learn about diabetes
microvascular complications and apply preventative strategies as early as
possible. Paradoxically, the diagnosis of a diabetes microvascular complication
in itself may represent a unique learning opportunity because 86% of participants
improved diabetes self-care after this event. Recommendations offer providers
simple but important clinical approaches to improve these difficult conversations
and thus support necessary behaviour changes and psychosocial well-being.
Training is needed to help providers discuss the threat of diabetes complications
with honest but positive messages so that people with diabetes can be fully
informed but also maintain hope in the face of complications.
PMID- 28703927
TI - Reducing the Primary Cesarean Birth Rate: A Quality Improvement Project.
AB - INTRODUCTION: Research continues to support vaginal birth as the safest mode of
childbirth, but despite this, cesarean birth has become the most common surgical
procedure performed on women. The rate has increased 500% since the 1970s without
a corresponding improvement in maternal or neonatal outcomes. A Colorado
community hospital recognized that its primary cesarean birth rate was higher
than national and state benchmark levels. To reduce this rate, the hospital
collaborated with its largest maternity care provider group to implement a select
number of physiologic birth practices and measure improvement in outcomes.
PROCESS: Using a pre- and postprocess measure study design, the quality
improvement project team identified and implemented 3 physiologic birth
parameters over a 12-month period that have been shown to promote vaginal birth.
These included reducing elective induction of labor in women less than 41 weeks'
gestation; standardizing triage to admit women at greater than or equal to 4 cm
dilation; and increasing the use of intermittent auscultation as opposed to
continuous fetal monitoring for fetal surveillance. The team also calculated each
obstetrician-gynecologist's primary cesarean birth rate monthly and delivered
these rates to the providers. OUTCOMES: Outcomes showed that the provider group
decreased its primary cesarean birth rate from 28.9% to 12.2% in the 12-month
postprocess measure period. The 57.8% decrease is statistically significant (odds
ratio [OR], 0.345; z = 6.52, P < .001; 95% confidence interval [CI], 0.249
0.479). DISCUSSION: While this quality improvement project cannot be translated
to other settings, promotion of physiologic birth practices, along with audit and
feedback, had a statistically significant impact on the primary cesarean birth
rate for this provider group and, consequently, on the community hospital where
they attend births.
PMID- 28703928
TI - Regulatory and pro-inflammatory cytokines in Brazilian living-related renal
transplant recipients according to creatinine plasma levels.
AB - AIM: The maintenance of stable graft function in renal transplanted recipients
(RTR) is a challenge for healthcare staff. The ideal biomarkers must have
significant predictive values to monitor the intricate renal function response
triggered after renal transplantation. The main purpose in this study was to
evaluate the regulatory and pro-inflammatory cytokines as biomarkers of allograft
function in living-related renal transplant patients. METHODS: Regulatory and pro
inflammatory cytokine plasma levels were measured by flow cytometry in 120 living
related renal transplanted patients categorized into three groups according to
creatinine plasma levels: creatinine less than 1.4 mg/dL (C1), creatinine within
1.4-2.0 mg/dL (C2) and more than 2.0 mg/dL (C3). Patients were also classified as
'low' or 'high' cytokine producers. Clinical data were obtained from patients'
medical record. RESULTS: We have found a peak of regulatory cytokines in RTR with
low creatinine levels as well as a peak of IL-6 pro-inflammatory cytokine in
patients with high creatinine levels. C1 and C3 groups showed a mixed pro
inflammatory (IL-8, IL-6, IL-1beta, TNF-alpha, IL-12 and IFN-gamma) and
regulatory (IL-4, IL-5 and IL-10) cytokine pattern and C2 had a predominant pro
inflammatory profile. C3 group showed a higher frequency of high pro-inflammatory
cytokine producers compared to C1. CONCLUSION: Our data suggest that regulatory
cytokines IL-4, IL-5 and IL-10 could be good biomarkers associated with stable
renal function, while pro-inflammatory cytokines seems to be potential markers in
RTR related to high creatinine plasma levels, specially IL-6 despite of its
borderline values.
PMID- 28703929
TI - Induction of Labor.
PMID- 28703930
TI - Bundle branch alternans with PR alternans. What is the mechanism?
PMID- 28703931
TI - Rationale and design of a randomized trial of apixaban vs warfarin to evaluate
atherosclerotic calcification and vulnerable plaque progression.
AB - Vitamin K antagonists (VKAs) are known to increase vascular calcification,
suggesting increased cardiovascular disease events. Apixaban is an oral direct
factor Xa inhibitor superior to warfarin at preventing stroke or systemic
embolism and may stabilize coronary atherosclerosis. The potential benefits of
avoiding VKA therapy and the favorable effects of factor Xa inhibitors could
contribute to cardiovascular disease event reduction. We hypothesized that
apixaban inhibits vascular calcification and coronary atherosclerosis progression
compared with warfarin in patients with atrial fibrillation (AF). This study is a
single-center, prospective, randomized, open-label study. From May 2014 to
December 2015, 66 patients with nonvalvular AF who experienced VKA therapy were
enrolled. Patients were randomized into either warfarin or apixaban cohorts and
followed for 52 weeks. The primary objective is to compare the rate of change in
coronary artery calcification (CAC) from baseline to follow-up in apixaban vs
warfarin cohorts. The key secondary objective is to compare the rate of incident
plaques and quantitative changes in plaque types between patients randomized to
either warfarin or apixaban cohorts using serial coronary computed tomography
angiography. Expert readers will blindly assess CAC and coronary artery plaques.
It is thought that this trial will result in significant differences in CAC and
coronary artery plaque progression between the VKA and apixaban. The results are
anticipated to provide a novel insight into treatment selection for AF patients.
The study is registered at http://www.clinicaltrials.gov (NCT 02090075).
PMID- 28703932
TI - Biomarkers in allergic asthma: Which matrix should we use?
PMID- 28703933
TI - Officer of the Order of the British Empire: P. L. Arnold / Robert T. Koch Gold
Medal: C. T. Walsh / Inhoffen Medal: H. Wennemers / OMCOS Award: Ruben Martin.
PMID- 28703934
TI - Analysis of cytochrome P450 contribution to evolved plant toxin resistance in
Drosophila sechellia.
AB - Drosophila sechellia is a dietary specialist species of fruit fly that has
evolved resistance to the toxic secondary defence compounds produced by the fruit
of its preferred host plant Morinda citrifolia. The genetic basis of adult toxin
resistance is the result of evolution at five loci across the genome. Genetic
mapping between D. sechellia and Drosophila simulans and subsequent functional
studies in Drosophila melanogaster have identified candidate genes potentially
underlying one locus involved in toxin resistance but the remainder of the genes
involved are unknown. Genes in the mixed function oxidase or cytochrome P450 gene
family are frequently utilized in evolved toxin resistance in insects, yet
whether they play a role in D. sechellia's resistance to the toxins found in its
host plant is unknown. Here we test the role of cytochrome P450 enzymatic
activity in evolved resistance to the two primary toxins found in M. citrifolia
fruit: octanoic acid and hexanoic acid. We found that although cytochrome P450
enzymatic activity is involved in basal resistance it is not involved in derived
toxin resistance in D. sechellia.
PMID- 28703935
TI - The effect of laparoscopic resection of large niches in the uterine caesarean
scar on symptoms, ultrasound findings and quality of life: a prospective cohort
study.
AB - OBJECTIVE: To evaluate the effectiveness of a laparoscopic niche resection on
niche-related symptoms and/or fertility-related problems, ultrasound findings and
quality of life. DESIGN: Prospective cohort study. SETTING: University hospital.
POPULATION: Women with a large niche (residual myometrium <3 mm) and complaints
of either postmenstrual spotting, dysmenorrhoea, intrauterine fluid accumulation
and/or difficulties with embryo transfer due to distorted anatomy. METHODS: Women
filled out questionnaires and a validated menstrual score chart at baseline and 6
months after the laparoscopic niche resection. At baseline and between 3 and 6
months follow up niches were evaluated by transvaginal ultrasound. MAIN OUTCOME
MEASURES: The primary outcome was reduction of the main problem 6 months after
the intervention. Secondary outcomes were complications, menstrual
characteristics, dysmenorrhoea, niche measurements, intrauterine fluid, surgical
outcomes, satisfaction and quality of life. RESULTS: In all, 101 women underwent
a laparoscopic niche resection. In 80 women (79.2%) the main problem was improved
or resolved. Postmenstrual spotting was significantly reduced by 7 days at 6
months follow up compared with baseline. Dysmenorrhoea and discomfort related to
spotting was also significantly reduced. The residual myometrium was increased
significantly at follow up. The intrauterine fluid was resolved in 86.9% of the
women with intrauterine fluid at baseline; 83.3% of women were (very) satisfied.
The physical component of quality of life increased, the mental component did not
change. CONCLUSIONS: A laparoscopic niche resection reduced postmenstrual
spotting, discomfort due to spotting, dysmenorrhoea and the presence of
intrauterine fluid in the majority of women and increased the residual
myometrium. TWEETABLE ABSTRACT: Laparoscopic niche resection reduces niche
related problems and enlarges the residual myometrium.
PMID- 28703936
TI - Randomized clinical trial of percutaneous tibial nerve stimulation versus sham
electrical stimulation in patients with faecal incontinence.
AB - BACKGROUND: The aim was to assess the effects of percutaneous tibial nerve
stimulation (PTNS) in the treatment of faecal incontinence (FI) by means of an
RCT. METHODS: Patients aged over 18 years with FI were included in a multicentre,
single-blinded RCT. The primary endpoint was reduction in the median or mean
number of FI episodes per week. Secondary endpoints were changes in measures of
FI severity, and disease-specific and generic quality of life. Outcomes were
compared between PTNS and sham stimulation after 9 weeks of treatment. RESULTS: A
higher proportion of patients in the PTNS (13 of 29) than in the sham (6 of 30)
group showed a reduction of at least 50 per cent in the median number of FI
episodes/week (incidence rate ratio (IRR) 2.40, 95 per cent c.i. 1.10 to 5.24; P
= 0.028), but not in the mean number of episodes/week (10 of 29 versus 8 of 30;
IRR 1.42, 0.69 to 2.92; P = 0.347). The absolute median number of FI episodes per
week decreased in the PTNS but not in the sham group (IRR 0.66, 0.44 to 0.98; P =
0.041), as did the mean number (IRR 0.65 (0.45 to 0.97); P = 0.034). Scores on
the Cleveland Clinic Florida faecal incontinence scale decreased significantly in
both groups, but more steeply in the PTNS group (mean difference -1.3, 95 per
cent c.i. -2.6 to 0.0; P = 0.049). The aggregated mental component score of Short
Form 36 improved in the PTNS but not in the sham group (mean difference 5.1, 0.5
to 9.6; P = 0.028). CONCLUSION: PTNS may offer a small advantage in the clinical
management of FI that is insufficiently responsive to conservative treatment. The
key challenge will be to identify patients who may benefit most from this
minimally invasive surgical procedure. Registration number: NCT00974909
(http://www.clinicaltrials.gov).
PMID- 28703939
TI - Adaptation of the By-Band randomized clinical trial to By-Band-Sleeve to include
a new intervention and maintain relevance of the study to practice.
AB - BACKGROUND: Recruitment into surgical RCTs can be threatened if new interventions
available outside the trial compete with those being evaluated. Adapting the
trial to include the new intervention may overcome this issue, yet this is not
often done in surgery. This paper describes the challenges, rationale and methods
for adapting an RCT to include a new intervention. METHODS: The By-Band study was
designed in the UK in 2009-2010 to compare the effectiveness of laparoscopic
adjustable gastric band and Roux-en-Y gastric bypass for severe obesity. It
contained a pilot phase to establish whether recruitment was possible, and the
grant proposal specified that an adaptation to include sleeve gastrectomy would
be considered if practice changed and recruitment was successful. Information on
changing obesity surgery practice, updated evidence and expert opinion about
trial design were used to inform the adaptation. RESULTS: The pilot phase
recruited over 13 months in 2013-2014 and randomized 80 patients (79
anticipated). During this time, major changes in obesity practice in the UK were
observed, with gastric band reducing from 32.6 to 15.8 per cent and sleeve
gastrectomy increasing from 9.0 to 28.1 per cent. The evidence base had not
changed markedly. The British Obesity and Metabolic Surgery Society and study
oversight committees supported an adaptation to include sleeve gastrectomy, and a
proposal to do so was approved by the funder. CONCLUSION: Adaptation of a two
group surgical RCT can allow evaluation of a third procedure and maintain
relevance of the RCT to practice. It also optimizes the use of existing trial
infrastructure to answer an additional important research question. Registration
number: ISRCTN00786323 (http://www.isrctn.com/).
PMID- 28703940
TI - Ebselen impairs cellular oxidative state and induces endoplasmic reticulum stress
and activation of crucial mitogen-activated protein kinases in pancreatic tumour
AR42J cells.
AB - Ebselen (2-phenyl-1,2-benzisoselenazol-3(2H)-one) is an organoselenium radical
scavenger compound, which has strong antioxidant and anti-inflammatory effects.
However, evidence suggests that this compound could exert deleterious actions on
cell physiology. In this study, we have analyzed the effect of ebselen on rat
pancreatic AR42J cells. Cytosolic free-Ca2+ concentration ([Ca2+ ]c ), cellular
oxidative status, setting of endoplasmic reticulum stress, and phosphorylation of
major mitogen-activated protein kinases were analyzed. Our results show that
ebselen evoked a concentration-dependent increase in [Ca2+ ]c . The compound
induced an increase in the generation of reactive oxygen species in the
mitochondria. We also observed an increase in global cysteine oxidation in the
presence of ebselen. In the presence of ebselen an impairment of cholecystokinin
evoked amylase release was noted. Moreover, involvement of the unfolded protein
response markers, ER chaperone and signaling regulator GRP78/BiP, eukaryotic
translation initiation factor 2alpha and X-box binding protein 1 was detected.
Finally, increases in the phosphorylation of SAPK/JNK, p38 MAPK, and p44/42 MAPK
in the presence of ebselen were also observed. Our results provide evidences for
an impairment of cellular oxidative state and enzyme secretion, the induction of
endoplasmic reticulum stress and the activation of crucial mitogen-activated
protein kinases in the presence of ebselen. As a consequence ebselen exerts a
potential toxic effect on AR42J cells.
PMID- 28703941
TI - Determination of the Absolute Configuration of (-)-Hydroxynitrilaphos and Related
Biosynthetic Questions.
AB - The ongoing search for bioactive natural products has led to the development of
new genome-based screening approaches to identify possible phosphonate producing
microorganisms. From the identified phosphonate producers, several until now
unknown phosphonic acid natural products were isolated, including
(hydroxy)nitrilaphos (4 and 5) and (hydroxy)phosphonocystoximate (7 and 6). We
present the synthesis of phosphonocystoximate via an aldoxime intermediate.
Chlorination and coupling with methyl N-acetylcysteinate furnished 6 after global
deprotection. The obtained experimental data confirm the previously assigned
structure of the natural product. We were also able to determine the absolute
configuration of (-)-hydroxynitrilaphos. Chiral resolution of diethyl
cyanohydroxymethylphosphonate (24) with Noe's lactol furnished both enantiomers
of 4. Conversion of (+)-24 to (R)-2-amino-1-hydroxyethylphosphonic acid by
reduction of the cyano-group showed (-)-hydroxynitrilaphos ultimately to be S
configured. Further, we present a 13 C-isotope labeling strategy for 4 and 5 that
will possibly solve the question of whether hydroxynitrilaphos is a biosynthetic
intermediate or a downstream product of hydroxyphosphonocystoximate biosynthesis.
PMID- 28703942
TI - Low-Temperature- and Phosphate Deficiency-Responsive Elements Control DGTT3
Expression in Chlamydomonas reinhardtii.
AB - acyl-CoA:Diacylglycerol acyltransferases (DGAT) catalyse the final step of the
triacylglycerol biosynthesis. Two major gene families have been shown to encode
DGATs, DGAT1, and DGAT2. Abiotic factors such as low temperatures, nitrogen, or
phosphorus deficiency was reported to play important roles in the growth and
development in green algae. Whether DGATs are induced by low temperatures or
phosphorus deficiency, and the corresponding promoter elements are not reported
yet. In this study, we found DGTT3 to have a significant response to low
temperatures, phosphorus deficiency, and other stresses, such as high
concentrations of NaCl, 20 MUM GA, and 20 MUM abscisic acid. The promoter element
of DGTT3 was then studied by deletion and scanning mutagenesis method. Results
revealed that the - 319/- 247 region is essential for low-temperature and
phosphate-deficiency-mediated induction of DGTT3 expression. The sequence from -
312 to - 299 of the CAATAGACTGCTGCT was the core sequence of the cold responsive
element, which facilitated the promoter response to cold induction. Meanwhile,
the sequence from - 319 to - 275 was critical to phosphate-deficiency regulation.
Furthermore, the relationship between DNA methylation and transgenic silence in
N condition was analyzed, and results showed that the DNA methylation rate of the
transformed insertion region was high. This phenomenon was responsible for the
decrease in ARS gene expression in the transgenic algal strain under -N
conditions.
PMID- 28703943
TI - Target-site resistance to acetolactate synthase (ALS)-inhibiting herbicides in
Amaranthus palmeri from Argentina.
AB - BACKGROUND: Herbicide-resistant weeds are a serious problem worldwide. Recently,
two populations of Amaranthus palmeri with suspected cross-resistance to
acetolactate synthase (ALS)-inhibiting herbicides (R1 and R2) were found by
farmers in two locations in Argentina (Vicuna Mackenna and Totoras,
respectively). We conducted studies to confirm and elucidate the mechanism of
resistance. RESULTS: We performed in vivo dose-response assays, and confirmed
that both populations had strong resistance to chlorimuron-ethyl, diclosulam and
imazethapyr when compared with a susceptible population (S). In vitro ALS
activity inhibition tests only indicated considerable resistance to imazethapyr
and chlorimuron-ethyl, indicating that other non-target mechanisms could be
involved in diclosulam resistance. Subsequently, molecular analysis of als
nucleotide sequences revealed three single base-pair mutations producing
substitutions in amino acids previously associated with resistance to ALS
inhibitors, A122, W574, and S653. CONCLUSION: This is the first report of als
resistance alleles in A. palmeri in Argentina. The data support the involvement
of a target-site mechanism of resistance to ALS-inhibiting herbicides. (c) 2017
Society of Chemical Industry.
PMID- 28703944
TI - Low-Dimensional Organic-Inorganic Halide Perovskite: Structure, Properties, and
Applications.
AB - Three-dimensional (3 D) perovskite has attracted a lot of attention owing to its
success in photovoltaic (PV) solar cells. However, one of its major crucial
issues lies in its stability, which has limited its commercialization. An
important property of organic-inorganic perovskite is the possibility of forming
a layered material by using long organic cations that do not fit into the
octahedral cage. These long organic cations act as a "barrier" that "caps" 3 D
perovskite to form the layered material. Controlling the number of perovskite
layers could provide a confined structure with chemical and physical properties
that are different from those of 3 D perovskite. This opens up a whole new batch
of interesting materials with huge potential for optoelectronic applications.
This Minireview presents the synthesis, properties, and structural orientation of
low-dimensional perovskite. It also discusses the progress of low-dimensional
perovskite in PV solar cells, which, to date, have performance comparable to that
of 3 D perovskite but with enhanced stability. Finally, the use of low
dimensional perovskite in light-emitting diodes (LEDs) and photodetectors is
discussed. The low-dimensional perovskites are promising candidates for LED
devices, mainly because of their high radiative recombination as a result of the
confined low-dimensional quantum well.
PMID- 28703945
TI - Safe Use of Atypical Antipsychotics in a Patient With Postpartum Psychosis and a
History of Seronegative Myasthenia Gravis.
PMID- 28703946
TI - Prevalence, Severity, and Correlates of Premenstrual Dysphoric Disorder Symptoms
Among Women in the Arabian Peninsula.
AB - Objective: To study the prevalence of premenstrual dysphoric disorder (PMDD)
symptom patterns among women in the United Arab Emirates and to measure the
debilitating nature of PMDD symptoms and sociodemographic correlates. Methods:
This cross-sectional sample study used the Mini-International Neuropsychiatric
Interview-Plus (MINI-Plus) and Premenstrual Symptoms Screening Tool (PSST) to
screen for presence and severity of PMDD symptoms in Arab women attending
ambulatory health services in Alain city, Emirate of Abu Dhabi, United Arab
Emirates, for routine health care between May 2005 and September 2005. Results:
The study participants include 508 women (76% Emiratis, 15% Omanis, and 8% other
Arabs) of childbearing age. In total, 94 women (18.6%) met MINI-Plus criteria for
PMDD; of these, 21 (4.1%) met PSST criteria for severe symptoms, 29 (5.7%) for
moderate symptoms, and 44 (8.7%) for mild or less symptoms. One woman (0.2%) with
severe symptoms and 12 women (2.4%) with moderate symptoms had negative MINI-Plus
scores. Presence of PMDD symptoms was significantly associated with higher
education (P = .000), single marital status (P = .001), major life stressors (P =
.001), and personal/family use of psychotropic medications (P = .000/P = .006),
personal/family psychological problems (P = .000/P = .001), irregular/painful
menses (P = .043/P = .001), and functional impairment on the Sheehan Disability
Scale (P = .000). Multilogistic regression analysis showed higher education,
major life stressor, personal use of psychotropic medications, personal/family
psychological problem, and painful menses were independent predictors of PMDD
symptoms. Conclusions: PMDD symptoms were common among the Arab women in our
study. The cyclically triggered mood disturbances were clustered in women with
personal/familial psychological problems, perhaps linking biologic constitution
to genetic predisposition for the development of PMDD symptomatology.
PMID- 28703947
TI - Insurance Coverage and Health Outcomes in Young Adults With Mental Illness
Following the Affordable Care Act Dependent Coverage Expansion.
AB - OBJECTIVE: As a provision of the Affordable Care Act, young adults were able to
remain on their parents' health insurance plans until age 26. We examined the
impact of the 2010 dependent coverage expansion on insurance coverage and health
outcomes among young adults with mental illness. METHODS: Data are from the 2008
2013 National Survey on Drug Use and Health, an annual population-based survey of
noninstitutionalized US individuals aged 12 and older. We used a difference-in
differences approach to compare young adults with mental illness subject to the
provision (aged 19-25 years, n = 19,051) with an older comparison group (aged 26
34 years, n = 7,958) before (2008-2009) and after (2011-2013) the dependent
coverage expansion in their insurance coverage, use of health services, and self
reported health. RESULTS: In adjusted analyses, following the dependent coverage
expansion, private insurance coverage increased by 11.7 percentage points (95%
CI, 8.4-15.1, P < .001) and uninsurance decreased by 8.9 percentage points (95%
CI, -12.1 to -5.7, P < .001) among 19- to 25-year-olds with mental illness,
relative to 26- to 34-year-olds. The provision was associated with a modest
increase in young adults with mental illness who received outpatient mental
health treatment at least monthly on average (+2.0% [95% CI, 0.1% to 4.0%, P =
.04]) and a modest decrease in those reporting their overall health as fair or
poor (-2.3% [95% CI, -4.6% to -0.0%, P = .05]). Unmet mental health needs due to
cost decreased significantly among those with moderate-to-serious mental illness
(-12.3% [95% CI, -22.7% to -2.0%, P = .02]), but did not change among those with
mild illness. CONCLUSIONS: The 2010 dependent coverage expansion was associated
with an increase in insurance coverage, several indicators of mental health
treatment, and improved self-reported health among young adults with mental
illness.
PMID- 28703948
TI - The Health-Promoting Effects of Insurance Coverage.
PMID- 28703949
TI - Psychotherapy Alone and Combined With Medication as Treatments for Bipolar II
Depression: A Randomized Controlled Trial.
AB - OBJECTIVE: Bipolar II disorder (BP-II) is associated with marked morbidity and
mortality. Quetiapine, the treatment with greatest evidence for efficacy in BP-II
depression, is associated with metabolic burden. Psychotherapy, a treatment with
few side effects, has not been systematically evaluated in BP-II. This study
compared psychotherapy plus placebo to psychotherapy plus pharmacotherapy as
treatments for BP-II depression. METHODS: From 2010 to 2015, unmedicated adults
(n = 92) with DSM-IV-TR BP-II depression were randomly assigned to weekly
sessions of Interpersonal and Social Rhythm Therapy (IPSRT) plus placebo or IPSRT
plus quetiapine and followed for 20 weeks. RESULTS: For primary outcomes, IPSRT +
quetiapine yielded significantly faster improvement on 17-item Hamilton
Depression Rating Scale (F1,115.4 = 3.924, P = .048) and greater improvement on
Young Mania Rating Scale (F58.5 = 4.242, P = .044) scores. Both groups, however,
improved significantly over time with comparable response rates (>= 50% reduction
in depression scores): 67.4% (62/92) in the entire sample, with no between-group
differences. Those randomly assigned to their preferred treatment were 4.5 times
more likely to respond (OR = 4.48, 95% CI = 1.20-16.77, P = .026). IPSRT +
quetiapine assignment was associated with significantly higher body mass index
over time (F67.96 = 6.671, P = .012) and rates of dry mouth (79% v. 58%; chi2 =
4.0, P = .046) and a trend toward more complaints of oversedation (100% vs 92%;
chi2 = 3.4, P = .063). CONCLUSIONS: IPSRT plus quetiapine resulted in greater
symptomatic improvement but also more side effects than IPSRT alone. A subset of
participants improved with IPSRT alone, although absence of an inactive
comparator limits interpretation of this finding. Receipt of preferred treatment
was associated with better outcomes. Harms, benefits, and preferences should be
considered when recommending treatments for BP-II depression. TRIAL REGISTRATION:
ClinicalTrials.gov identifier: NCT01133821.
PMID- 28703950
TI - Randomized Controlled Trial of Web-Based Psychoeducation for Women With
Borderline Personality Disorder.
AB - OBJECTIVE: To determine if internet-based psychoeducation for borderline
personality disorder is effective in reducing symptom severity and improving
psychosocial functioning. METHODS: Eighty women who met DSM-IV criteria for
borderline personality disorder were randomly assigned either to the internet
based psychoeducation treatment group (n = 40) or to the internet-based control
group with no psychoeducation (n = 40). Recruitment was conducted from July 2013
to March 2015. Subjects participated in 15 assessment periods that were divided
into an acute phase (weeks 1-12) and a maintenance phase (months 6, 9, and 12).
Main outcomes were assessed using the Zanarini Rating Scale for Borderline
Personality Disorder. RESULTS: In the acute phase, women in the treatment group
were found to have a significant decline in their scores on all 10 outcomes
studied, while women in the control group had a significant decline on 7 of these
outcomes. Two between-group differences were found to be significant-those in the
treatment group reported a significantly greater decline in their impulsivity (z
= -1.98, P = .048) and a significantly greater increase in their psychosocial
functioning (z = -1.97, P = .049) than those in the control group. In the
maintenance phase, those in the treatment group were found to have a significant
decline in their scores on 9 of the 10 outcomes studied, while those in the
control group had a significant decline in 3 of these outcomes. In terms of
between-group differences, those in the treatment group reported a significantly
greater decline in all 5 studied areas of borderline psychopathology: affective
symptoms (z = -2.31, P = .021), cognitive symptoms (z = -3.20, P = .001),
impulsivity (z = -2.44, P = .015), interpersonal difficulties (z = -2.15, P =
.032), and overall borderline personality disorder symptoms (z = -2.11, P =
.035). CONCLUSIONS: Taken together, these results suggest that internet-based
psychoeducation is an effective form of early treatment for reducing the symptom
severity of borderline personality disorder for periods up to 1 year. TRIAL
REGISTRATION: ClinicalTrials.gov identifier: NCT01719731.
PMID- 28703951
TI - Secondary Prevention of Chronic PTSD by Early and Short-Term Administration of
Escitalopram: A Prospective Randomized, Placebo-Controlled, Double-Blind Trial.
AB - OBJECTIVE: Prospective studies have not identified a viable pharmacologic
strategy for secondary prevention of posttraumatic stress disorder (PTSD). The
authors examined whether preventive intervention via early and short-term
administration of a selective serotonin reuptake inhibitor (SSRI), within 1 month
of exposure to a traumatic event (before diagnosis of PTSD could be made), may
reduce the severity of PTSD symptoms according to DSM-IV at 13 months' follow-up.
METHODS: Over 25,000 screening calls to patients referred to an emergency
department for a traumatic event performed between June 2006 and December 2008
yielded 353 participants who were recruited within the month following a
traumatic event . Participants were randomly assigned in a double-blind design to
escitalopram (n = 176) or placebo (n = 177). The per-protocol analysis comprised
198 participants (escitalopram, n = 102; placebo, n = 96) who received treatment
for 12 to 24 weeks and were available for follow-up at week 56. RESULTS: The
primary outcome measure, the Clinician Administered PTSD Scale (CAPS), revealed
no prevention effect. However, a secondary outcome, the Pittsburgh Sleep Quality
Inventory (PSQI), showed better results for the SSRI group than for the placebo
group. For a subset of participants who experienced intentional trauma (missile
attacks, rape, or physical assault; n = 50), the prevention effect was found on
both primary and secondary measures (CAPS, PSQI and measures of depression and
global illness severity). CONCLUSIONS: Early and short-term administration of
escitalopram was not shown to prevent PTSD, although it did improve sleep
quality. In a subgroup of participants who experienced intentional trauma,
however, this early-treatment approach may be effective as secondary prevention.
This large study is the first to investigate the preventive effect of early
administration of escitalopram on PTSD. It highlights the relevance of the type
of trauma (intentional vs unintentional) to the outcome. TRIAL REGISTRATION:
ClinicalTrials.gov identifier: NCT00300313.
PMID- 28703952
TI - Potential of bacteriocins from lab to improve microbial quality of dry-cured and
fermented meat products.
AB - Meat and meat products are an important component of the daily diet.
Nevertheless, they are perishable goods and are prone to microbial contamination,
which leads to an increased risk to the health of consumers as well as economic
losses in the meat industry. Fermentation has been used for thousands of years to
preserve meat. As a result of extensive biochemical reactions occurring in meat
during fermentation and ripening, the condi- tions inhibiting the growth of
pathogenic and spoilage bacteria are formed. These changes are catalyzed by
endogenous meat enzymes and exogenous enzymes derived from natural contaminating
bacteria or starter cultures applied. In dry-cured and fermented meat products
they are represented mainly by lactic acid bacte- ria (LAB) that produce a wide
range of compounds, such as bacteriocins, directed against other microorgan-
isms. The use of bactericidal peptides does not affect the sensory quality of
foodstuffs, so that they attract attention as alternative means of preserving the
stability and safety of dry-cured products.
PMID- 28703953
TI - The effect of temperature on in vitro digestibility, fat globular size and free
fatty acid bio-availability in milk fat.
AB - BACKGROUND: The rate at which a particular fat is digested has an effect on its
bioavailability and on the lipid profile of the blood. Milk fat is a very complex
mixture of triacylglycerols, resulting in a very wide melting range (from
–40 to +40°C). Because temperature has a pronounced effect on the
physicochemical state of milk fat (i.e. crystallisation of different fat
fractions), this study analysed the bioavailability of milk fat at different
temperatures. METHODS: A simplified model simulating digestion in the intestine
at various temperatures was used. The released fatty acids and the changes in the
emulsion of milk fat under the effect of lipase were compared. RESULTS: The
amount and profiles of the released fatty acids varied depending on the
incubation temperature of the studied sample. At lower temperatures, the
fractions which were hydrolysed to a greater degree were those which contained
more unsaturated oleic acid, but contained less C14, C16 and C18 saturated acids.
Changes in the emulsion system also differed depending on temperature.
CONCLUSIONS: The obtained results indicate that, depending on the temperature,
not only different amounts, but also different fractions of milk fat were
hydrolysed by lipase, which indicates the role of the physico- chemical state of
milk fat during its digestion.
PMID- 28703954
TI - Evaluation of selected properties of gluten-free instant gruels processed under
various extrusion-cook- ing conditions.
AB - BACKGROUND: For consumers suffering with gluten intolerance, the only way to
manage the condition is to avoid foods which are high in gluten. Instant gruels,
processed from gluten-free corn and rice by extrusion cooking, could be used as a
ready meal both for children and for adults on a gluten-free diet. The aim of the
study was to evaluate the effects of various processing conditions on selected
characteristics of corn-rice instant gruels. METHODS: Corn-rice mixtures (75:25
and 50:50) were processed at 12, 14, 16 and 18% of initial moisture content,
using an extruder with screw speeds of 80, 100 and 120 rpm. Bulk density, water
absorption and solubility, gel formation, color and sensory characteristics were
assessed, under various pro- cessing conditions and with various corn:rice
ratios. RESULTS: The composition of the raw materials, initial moisture content
and screw speed applied during processing affected the characteristics of the
corn-rice extruded instant gruels. Increasing the amount of rice in the recipe
from 25 to 50% resulted in decreased bulk density, water solubility, volumetric
gel formation ability and b* value. Increasing the initial moisture content
increased the bulk density, L*, a* and b* intensity, and gel formation index
values of extrudates made with a 75:25 corn-rice recipe. Increased rpm increased
extrudate solubility and water absorption, if the initial moisture content was
higher than 14%. The highest scores for overall acceptability were found for milk
suspensions of 75:25 and 50:50 corn-rice instant gruels processed at 12 and 14%
of initial moisture content, at 120 rpm. CONCLUSIONS: Corn-rice instant gruels
can be successfully produced by extrusion-cooking. Variable param- eters, like
the initial moisture content of raw materials or screw speed during processing
significantly affected the properties of the products. An understanding of the
effects of processing conditions on some qualities of extruded instant gruels
allows more desirable products to be created. Moreover, the various components
can be used for extruded products for consumers on gluten-free diets. Functional
additives incorporated in the recipe to improve the nutritional value of the
extrudates, which will be investigated in our upcoming research.
PMID- 28703955
TI - Yield of acid curd cheese produced from cow's milk from different lactation
periods.
AB - BACKGROUND: Milk production intensification has led in many countries, including
Poland, to increased milk yields per cow. A higher milk yield resulted in changes
in cow productivity, including extended lactations. There is a paucity of
information on the quality of milk harvested during the last months of lactations
exceed- ing 10 months. Production capacity cheese (“cheese
expenditure”) is an important parameter of providing a recovery as much
as the possible components of the milk processed are dry substances, which in
turn af- fects the economics of production. The aim of the study was to determine
the influence of the lactation period (from standard lactation; extended
lactation phase) on the performance of the acid curd cheese. the relation- ship
between total protein content and acidity of fresh milk collected in two separate
periods of lactation on the yield of acid cheese was also evaluated. METHODS: The
study included 1384 samples of milk collected from Polish Holstein-Friesian cows,
the Black-White variety. The basic chemical composition of fresh milk and acid
curd cheese produced in the laboratory were analyzed. The cheese milk yield was
evaluated on the basis of the quantity of the re- sulting curd mass. RESULTS:
According to our estimates, under laboratory conditions an average of 100 kg of
milk per cow in population produced an estimated 20.1 kg of curd cheese. The
basic chemical composition of raw milk, which was diverse in terms of the period
of lactation, showed a higher dry matter, fat and protein content in milk
acquired during the extension phase of lactation compared to the milk of standard
lactation. It has been found that the lower titratable acidity of fresh milk
appeared with a higher yield of cheese curd. This difference was between 1.76 kg
(with milk from cows milked during the extended lactation phase) to 2.72 kg from
100 kg of cheese milk (milk with the standard lactation). Thus, the optimum level
of titratable acidity of milk for cheese yield is 6.0–7.5°SH.
CONCLUSIONS: Most samples with the highest yields of acid curd cheese (>20%) were
obtained from the milk from collected in the period from day 306 till the end of
lactation (60.54%).
PMID- 28703956
TI - Optimization of mooseer (A. hirtifolium Boiss.) dehydration under infrared
conditions.
AB - BACKGROUND: In recent years, infrared drying has gained popularity as an
alternative drying method for a va- riety of agricultural products. The use of
infrared radiation technology in drying agricultural products has several
advantages. These may include decreased drying time, high energy efficiency, high
quality finished products and uniform temperature in the product. With
intermittent infrared and convection heating of a thick porous material, the
drying time can be reduced compared to convection alone, while keeping good food
quality and high energy efficiency. METHODS: Response surface methodology (RSM)
was employed to optimize the drying con- ditions of mooseer under infrared
convective drying. Experiments were performed at air temperatures of 40, 55 and
70°C, infrared powers of 500, 1000 and 1500 W, air velocities of 0.5, 1.5 and
2.5 m/s and slice thicknesses of 2, 4, and 6 mm. In this study, effective
moisture diffusivity (Deff), shrinkage, color changes and specific energy
consumption (SEC) were investigated. The central composite design (CCD) was
selected for the design and optimization of the process. RESULTS: Deff was
obtained between 1.4×10 and 3.57×10 m /s. With increasing air
temperature and slice –10 –9 2 thickness, Deff also increased. The
level of shrinkage rose as slice thickness increased. The highest and lowest
values of color changes were calculated at air temperatures of 70°C (52.3%)
and 40°C (5.65%), respectively. Increasing air velocity led to an increase in
SEC. CONCLUSIONS: Optimum conditions for mooseer drying were achieved at air
temperature of 70°C, infrared power of 867.46, air velocity of 0.59 m/s and
slice thickness of 2 mm. At this point, Deff, shrinkage, color changes and SEC
was obtained as 1.32×10–9 m2/s, 29.58%, 17.62% and 4.64 MJ/kg,
respectively. The desir- ability value of 0.689 was achieved for the drying
process. .
PMID- 28703957
TI - Lactose-free frozen yogurt: production and characteristics.
AB - BACKGROUND: Nowadays, consumer demand is driving better and more nutritious dairy
products. Changing from traditional to new lactose-free products poses
technological challenges for the food industry in order to maintain or improve
their food characteristics and consumer preferences. METHODS: This study
investigates the production of lactose-free frozen yogurt by enzymati- cally
hydrolysis of lactose, and its influence on the final product characteristics. In
the case of lactose-free products, commercial Ha-lactase® was used for
hydrolysis, and the reaction occurred simultaneously with fermentation. The
effect of lactose hydrolysis on the physicochemical properties, texture,
viscosity, overrun and sensory attributes in the final product was investigated.
RESULTS: After yogurt maturation, the acidity of the lactose-free product was
significantly higher than in the control, suggesting that breaking down lactose
enhances the fermentation process. Lactose-free frozen yogurt had significantly
lower hardness and stickiness and higher viscosity than control frozen yogurt.
Moreover, lactose hydrolysis promoted a smooth and creamy consistency, whereas in
the case of conventional prod- ucts a coarse structure, due to the presence of
large ice crystals, was identified. Hydrolysis of lactose also improved the
sweetness and brightness of frozen yogurt. The improved textural properties of
lactose-free product results from the fact that monosaccharides produced during
lactose hydrolysis depress the freezing point of the mix, which enables product
with softer structure and bigger resistance to ice recrystallization to be
obtained. CONCLUSIONS: The study showed that lactose-free frozen yogurt may be
used successfully for production of novel lactose-free frozen desserts. Lactose
hydrolysis improves the texture and viscosity of the product, as well as
enhancing its sensory quality.
PMID- 28703958
TI - The potential use of probiotic strains Lactobacillus acidophilus NRRL B 4495,
Bifidobacterium bifidum NRRL B41410 in “Lor Whey Cheese” and the
effects on sensory properties.
AB - BACKGROUND: In recent years, probiotic bacteria have increasingly been
incorporated into various foods as dietary adjuncts. The viability of the
probiotic bacteria Lactobacillus acidophilus NRRL B 4495 and Bifido- bacterium
bifidum NRRL B41410 in salted (1% w/w) and unsalted lor whey cheese during
storage (21 days) at a refrigerated temperature (4°C) was evaluated. METHODS:
As well as the survival of the probiotic bacteria, total mesophilic bacteria,
total lactic acid bacteria, Pseudomonas spp., yeast-mould counts and sensory
characteristics were examined in the lor samples. RESULTS: The Bf. bifidum
remained in large numbers, at 7.30 and 7.11 log cfu/g, and Lb. acidophilus also
survived well, with counts of 7.60 and 7.47 log cfu/g, for unsalted and salted
cheeses respectively. Salted lor cheeses with added Lb. acidophilus have the
highest sensory scores in the groups. CONCLUSIONS: “Lor” whey cheese
showed good probiotic properties.
PMID- 28703959
TI - Effects of operative conditions on products obtained of starch-oil mixtures by
single-screw extrusion.
AB - BACKGROUND: d. The aim of the study was to evaluate the fat binding and
physicochemical properties of the products under conditions of potato starch
extrusion containing rapeseed or linseed oil and rapeseed oil with glycerol.
METHODS: The study dealt with the extrudates of potato starch produced with the
addition of rape seed or linseed oil and rapeseed oil and glycerol at 22%
humidity. The extrudates were obtained at two screw speeds: 80 rpm and 100 rpm.
Extrudates containing rapeseed oil and glycerol (R6G) were obtained at a
temperature distribution of 115/130/150°C, while those with the participation
of rapeseed oil and linseed oil were obtained at 120/135/128°C. Water
solubility index (WSI), water absorption index (WAI), specific surface area
(SBET) and quantity of fat permanently bound were determined for the products
obtained. RESULTS: When oils were added, the solubility of extrudates decreased
as compared to the control samples (starch without oil; S). Rapeseed oil added to
the starch mixture at the levels of 3 g and 6 g in had no sig- nificant effect on
the solubility of the product and amounted to: 80.3–82.6% and
78–79.6%. The largest decrease in solubility (WSI, 55.4–57.1%) was
demonstrated for samples with 6% addition of rapeseed oil and 10 g glycerol. For
these samples (R6G), a significant increase in the index WAI (376–397%) was
recorded. Extrudates obtained with the addition of 3 g of rapeseed oil absorbed
slightly more water than those with 6 g of oil added. The specific surface area
(SBET 230–256 m2/g) determined from the water vapor adsorption isotherm
indicates no statistically significant difference at α = 0.05 for products
with rapeseed oil, linseed oil, and controls. A significant increase in the
specific surface area (SBET 284–347 m2/g) was observed for samples with 6g
rapeseed oil and 10 g glycerol added. For samples with 3 g of rapeseed oil, the
amount of bound fat was 1.9–2.1 g/100 g of starch and for 6% the starch
percentage was 2.96–3.5 g/100 g. CONCLUSIONS: The water solubility of
starch extrudates with the addition of oils decreases with an increase in screw
speed. Starch extrudates with linseed oil and rapeseed oil plus added glycerol
are characterized by an increase in water-absorption capacity with respect to the
control extrudates. The products obtained with the addition of rapeseed oil and
glycerol exhibit a significant increase in their specific surface area. The quan-
tity of fat permanently bound during extrusion depended on: the oil type, its
percentage in the mixture and the screw speed. The linseed oil was the least
absorbed in the starch structure, but rapeseed oil binding increased with the
increase in its level in the mixture.
PMID- 28703960
TI - Antioxidative properties of milk protein preparations fermented by Polish strains
of Lactobacillus helveticus.
AB - BACKGROUND: The increasing significance of food products containing substances
with antioxidative activi- ties is currently being observed. This is mainly due
to the fact that pathogenic changes underlying some diseases are related to the
carcinogenic effects of free radicals. Antioxidative compounds play an important
role in supporting and enhancing the body’s defense mechanisms, which is
useful in preventing some civili- zation diseases. Unfortunately, it has been
already proved that some synthetic antioxidants pose a potential risk in vivo.
Therefore, antioxidant compounds derived from a natural source are extremely
valuable. Milk is a source of biologically active precursors, which when enclosed
in structural protein sequences are inactive. The hydrolysis process, involving
bacterial proteolytic enzymes, might release biopeptides that act in various
ways, including having antioxidant properties. The objective of this study was to
determine the antioxidant properties of milk protein preparations fermented by
Polish strains of L. helveticus. The research also focused on evaluating the
dynamics of milk acidification by these strains and analyzing the textural
properties of the skim milk fermented products obtained. METHODS: The research
studied Polish strains of L. helveticus: B734, 141, T80 and T105, which have not
yet been used industrially. The antioxidant properties of 1% (w/v) solutions of
milk protein preparations (skim milk powder, caseinoglycomacropeptide and α
lactoalbumin) fermented by these strains were determined by neutralizing the free
radicals with 2,2-diphenyl-1-picrylhydrazyl (DPPH). Moreover, solutions of skim
milk powder (SMP) fermented by the microorganisms being tested were analyzed on
gel electrophoresis (SDS-PAGE). The dynamics of milk acidification by these
microorganisms was also analyzed L. helveticus strains were used to prepare
fermented regenerated skim milk products that were subjected to texture profile
analysis (TPA) performed using a TA-XT2i (Stable Micro Systems, Godalming, UK).
RESULTS: The results suggest that the antioxidant activity of fermented milk
protein preparations depended on the type of milk protein preparation and was
also related to the strain that conducted the fermentation process. The process
of caseinoglycomacropeptide (CGMP) fermentation by DSMZ 20075, T105 and 141
signifi- cantly (p < 0.05) influenced the increase in the antioxidant activities
of the protein preparation, the highest values of parameter were obtained in
samples fermented by L. helveticus T105 (64.82 ±0.013%), while in the case
of α-lactoalbumin (α-la), the strongest free radical scavenging
activity (66.67 ±0.020%) was noted for unfermented samples (control).
CONCLUSIONS: The greatest increase in DPPH scavenging activity (% of inhibition)
was noted for fermented SMP solutions. The highest values of the parameter
measured were recorded for SMP fermented by the reference strain (85.98
±0.009%) and T80 (81.66 ±0.013%). Strain T105 demonstrated the most
desirable properties with respect to milk acidifying dynamic and texture
properties of fermented skim milk products, while the reference strain (L.
helveticus DSMZ 20075) and L. helveticus T80 seem to be more desirable in terms
of the possibility of obtaining fermented protein preparations with the best
antioxidant properties. The Polish strains analyzed here might find application
in dairy products and also in developing functional food products. Furthermore,
the preparations of milk protein that were fermented by the strains being tested
may be a natural source dietary antioxidants.
PMID- 28703961
TI - Effect of addition of wild garlic (Allium ursinum) on the quality of kefirs from
sheep's milk.
AB - BACKGROUND: Sheep’s milk has a high content of total solids, which
qualifies it as a very good raw material for the production of fermented milk
drinks. Currently, there are commercially produced kefirs and yogurts from
sheep’s milk in the countries of the Mediterranean region. The growing
interest in the consumption of these products is justified not only by their
taste merits, but also because of their health-promoting proper- ties. The aim of
the present study was to determine the effect of the addition of 1% of
lyophilized wild garlic powder on the properties of kefirs from sheep’s
milk. METHODS: Sheep’s milk was pasteurized (85°C, 30 min), cooled
down, enriched with 1% of freeze-dried wild garlic powder, inoculated with a
Commercial VITAL kefir culture and fermented for 16 hours (26°C). The
influence of wild garlic on acidity (pH, °SH), syneresis (%), texture (TPA
test), colour (L*a*b*) and the sensory profile of kefirs was conducted. RESULTS:
Wild garlic could be used as a taste and flavour modifier in the production of
kefir from sheep’s milk. The addition of 1% of freeze-dried wild garlic
slowed down the fermentation of kefir, changed colour and reduced syneresis.
CONCLUSIONS: Wild garlic could be used as a valuable supplement and a modifier of
taste and flavour in kefir from sheep’s milk.
PMID- 28703962
TI - Haematological and biochemical studies on Justicia carnea leaves extract in
phenylhydrazine induced-anemia in albino rats.
AB - BACKGROUND: Justicia carnea is a medicinal plant used widely in Nigeria which is
reported to have diverse functions, including blood-boosting potential. Aim. The
effect of the ethanol extract of Justicea carnea (JC) leaves in phenylhydrazine
induced-anemia albino rats on haematological and lipid profile parameters was
investigated. METHODS: The experimental animals were randomly grouped into five
groups of six rats each – group 1 (non-anemic control), group 2 (anemic
control), group 3 (500 mg/kg of JC extract), group 4 (1000 mg/kg of JC extract)
and group 5 (DMSO control). Phenylhydrazine was administered once at a dose of 80
mg/kg b.w. to induce hemolytic anemia. After 28 days of extract administration,
they were humanely sacrificed and the serum collected was used for biochemical
analysis. RESULTS: In the acute toxicity study, the LD50 was found to be above
5000 mg/kg body weight. Packed Cell Volume (PCV) values, Red Blood cell (RBC) and
haemoglobin (Hb) concentrations decreased (p < 0.05) sig- nificantly after 48
hours of phenylhydrazine induction, but after 28 days of administering extracts
of Justicia carnea, PCV values, RBC and Hb increased (p < 0.05) significantly.
There were significant (p < 0.05) de- creases in cholesterol, triacylglycerol,
and LDL cholesterol concentrations in the extract-administered groups (groups
3&4) relative to the anemic control. There was a significant (p < 0.05) increase
in HDL-cholesterol concentrations in the extract groups (3&4) relative to the non
anemic control. CONCLUSIONS: Extracts of Justicia carnea not only reversed anemic
conditions in the phenylhydrazine-induced rats, it also improved the lipid
profile, and this may be attributed to its rich phytochemical, nutrient and vita-
min composition. Therefore, the findings of the study suggest that J. carnea
leaves could be used to manage lipid abnormalities associated with anemia.
PMID- 28703964
TI - ?
PMID- 28703963
TI - Comparing the effects of sucrose and high-fructose corn syrup on lipid metabolism
and the risk of cardiovascular disease in male rats.
AB - BACKGROUND: The objective of this study was to compare, in an animal model, the
effect of different sugar types (sucrose vs. high-fructose corn syrup 55%)
consumed as 10% by weight of the diet (11.6% of daily caloric intake) on the
amount of food consumed, body weight, fatty tissue deposits, concentrations of
selected lipids, and atherogenic indices of blood plasma. Material and method.
The experiment was carried out on 30 5-month-old Wistar male rats, fed three
differ- ent diets, containing, amongst other foods, (1) ground unrefined cereal
grains, (2) sucrose, (3) high-fructose corn syrup. Results. Weight gains in
animals on sucrose or high-fructose corn syrup diets were higher than those con-
suming basic feed, but the effect was not associated with perivisceral fat
accumulation. It has been found that all the atherogenic indices
(Castelli’s Risk Index I, Castelli’s Risk Index II, Atherogenic Index
of Plasma, Atherogenic Coefficient) were statistically significantly higher in
animals on a high-fructose corn syrup diet compared to both the control group and
those on a sucrose diet. Conclusion. The effect of the 55% high-fructose corn
syrup on the tested parameters of lipid metabolism was not equivalent to that of
sucrose. Using HFCS-55 instead of sucrose has an adverse effect on blood lipid
parameters, while weight gains and peri-organ fat deposits are comparable.
Moreover, the obtained results confirm that tested animals were susceptible to
the adverse effects of sugars added to their diet, even in small amounts. This
emphasises the need to precisely control the amount of added sugars in. METHODS:
nd. The objective of this study was to compare, in an animal model, the effect of
different sugar types (sucrose vs. high-fructose corn syrup 55%) consumed as 10%
by weight of the diet (11.6% of daily caloric intake) on the amount of food
consumed, body weight, fatty tissue deposits, concentrations of selected lipids,
and atherogenic indices of blood plasma. Material and method. The experiment was
carried out on 30 5-month-old Wistar male rats, fed three differ- ent diets,
containing, amongst other foods, (1) ground unrefined cereal grains, (2) sucrose,
(3) high-fructose corn syrup. RESULTS: Weight gains in animals on sucrose or high
fructose corn syrup diets were higher than those con- suming basic feed, but the
effect was not associated with perivisceral fat accumulation. It has been found
that all the atherogenic indices (Castelli’s Risk Index I, Castelli’s
Risk Index II, Atherogenic Index of Plasma, Atherogenic Coefficient) were
statistically significantly higher in animals on a high-fructose corn syrup diet
compared to both the control group and those on a sucrose diet. CONCLUSIONS: The
effect of the 55% high-fructose corn syrup on the tested parameters of lipid
metabolism was not equivalent to that of sucrose. Using HFCS-55 instead of
sucrose has an adverse effect on blood lipid parameters, while weight gains and
peri-organ fat deposits are comparable. Moreover, the obtained results confirm
that tested animals were susceptible to the adverse effects of sugars added to
their diet, even in small amounts. This emphasises the need to precisely control
the amount of added sugars in the diet.
PMID- 28703965
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PMID- 28703966
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PMID- 28703967
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PMID- 28703968
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PMID- 28703969
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PMID- 28703971
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PMID- 28703974
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PMID- 28703984
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PMID- 28703985
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PMID- 28703986
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PMID- 28703987
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PMID- 28703988
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PMID- 28703989
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PMID- 28703990
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PMID- 28703991
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PMID- 28703992
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PMID- 28703993
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PMID- 28703994
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PMID- 28703995
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PMID- 28703996
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PMID- 28703997
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PMID- 28703998
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PMID- 28703999
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PMID- 28704000
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PMID- 28704001
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PMID- 28704002
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PMID- 28704003
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PMID- 28704004
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PMID- 28704005
TI - [Repetition of blood testing : which risks for the patient?]
AB - Numerous tests are performed in the hospital, often on a daily basis. These tests
should answer a specific scientific question and be performed only if their
results can have an impact on patient care. In addition to causing anemia,
overutilization of tests, such as useless blood testing, can have a deleterious
impact on the patients because they carry the risk of false positive results,
which can trigger downstream unnecessary investigations and costs.
PMID- 28704006
TI - [Urinary catheter : comply with guidelines to avoid infections].
AB - Catheter-associated urinary tract infection (CAUTI) is the most frequent hospital
acquired infection, associated with significant morbidity, mortality and health
care costs. Up to 50 % of urinary catheter use in hospital are for incontinence
or convenience without proper indication. In addition, urinary catheters are not
removed when no longer necessary, due to a lack of vigilance of the health care
team. The duration of catheterization is the most important risk factor for the
development of CAUTI. Simple measures to prevent CAUTI include appropriate use,
maintaining awareness of catheters in place and use of different alternatives.
These measures can reduce the number of CAUTI over 50 % along with positive
impact on the quality of care and costs.
PMID- 28704007
TI - [Blood transfusion : optimizing the use of a scarce and expensive resource].
AB - Haemoglobin transfusion threshold remains debated with a high variability of
practice among physicians. Several well-conducted studies revealed that a liberal
transfusion policy is not only unnecessary, but can also prove harmful in certain
situations. Blood transfusion is a costly act involving risks of infection,
allergic and hemodynamic. Optimizing the use of this scarce and expensive
resource becomes necessary. This article summarizes the different transfusion
thresholds to respect in hospital clinical practice, based on the latest
international recommendations, while emphasizing the importance of clinical
judgment in each situation.
PMID- 28704008
TI - [Can mobilization preserve the elderly hospitalized from functional decline ?]
AB - Up to 65% of older adults who walk independently will lose this capacity during a
hospital stay. In older adults, loss of walking independence increases the length
of hospital stay, the need for rehabilitation services and for
institutionalization, as well as the risk of falls (during hospital stay and
after discharge) and the risk of death. Bed rest or limited walking during a
hospital stay causes deconditioning and is one of the primary risk factors for
loss of independence and adverse outcome in hospitalized older adults. Because
early mobilisation improves the autonomy and outcomes in elderly patients, it is
of major importance that all healthcare workers pay attention to that measure of
care.
PMID- 28704009
TI - [Benzodiazepines in elderly patients : the dark side of a magic pill].
AB - Clinical studies show that prescription of benzodiazepines increases with age,
and well outside of recognized indications. It often is inappropriate and
abusive. Its consequences can be very serious and considerably increase patients'
morbidity and mortality. Strategies exist to stop these medications through a
multidisciplinary approach. Widespread campaigns are necessary to correct what
has become a significant public health problem.
PMID- 28704010
TI - [Smarter medicine in ambulatory care : beliefs and practices of family doctors
and training of future clinicians].
AB - Following an American and then international initiative, the Swiss Society of
Internal Medicine launched the " Smarter Medicine " campaign in 2014 with five
recommendations of activities to be avoided, focusing on low back pain,
antibiotic prescriptions, pre-operative chest x-rays, prostate cancer screening
and treatment with proton pump inhibitors. In 2016, 69 % of family physicians
reported that they knew the recommendations and levels of agreement were very
high. However, physicians reported differences between recommendations in how
often they are followed in practice, and there remains room for improvement. We
need to put in place training programs at the pre- and post-graduate levels, as
well as continuing medical education. It would also be useful to educate
patients.
PMID- 28704011
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PMID- 28704012
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PMID- 28704013
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PMID- 28704014
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PMID- 28704015
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PMID- 28704016
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PMID- 28704017
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PMID- 28704018
TI - Ribavirin treatment of a patient with chronic hepatitis E.First case reported in
Latin America.
AB - We describe a clinical case of a kidney transplant patient whopresented a sudden
elevation of his liver function tests. Oncewe ruled out the most frequent causes
of acute hepatitis, serumtests for Hepatitis E were performed. Hepatitis E
virusRNA was detected in blood and stools. After six months thevirus was still
detected. Ribavirin treatment was initiatedwith normalization of the serum
aminotransferases and sustainedvirology response was achieved.
PMID- 28704019
TI - [Diagnosis of acute pancreatitis].
PMID- 28704020
TI - Surgical or Transcatheter Aortic-Valve Replacement.
PMID- 28704022
TI - [Prevention of cancer colorectal. From stone age to the cornerstone].
PMID- 28704023
TI - [Overweight and obesity: review and update].
AB - : Obesity is an epidemic with important health repercussionsin addition to high
treatment-related costs. Between 2006and 2007 the WHO developed new assessment
tools, whicharen't being globally used. In fact, there is no unified
problemmanagement across the hemisphere. Objectives: To updateobesity
epidemiology, to promote application of WHO'sstandards, to review new findings on
physiopathology (i.e.,fatty tissue as endocrine organ, intestinal microbiota),
toupdate epidemiological information, and to provide managementguidelines that
can be integrated in clinical care. Methods: LAPSGHAN called up its members to
collaboratein preparing this review article under the direction ofan
editor/coordinator, who selected the contents and literaturewith the best
evidencetogether with the members. Eachmember prepared a separate document for
each content. Thechosen contents were later collated, unified, and edited.
Results.This documents highlights the following: 1) Althoughextreme obesity is
increasing in the US, overweight and obesityprevalence has stabilized, while in
other countries it isalarmingly increasing; 2) New information regarding role
offatty tissue as endocrine organ and self-regulator of obesity;3) The promising
role of microbiota; and 4) Guidelines forchildren handling during consultation
and follow-up. Conclusions: There is no widespread implementation of standardsand
guidelines from the World Health Organization(WHO). There is no agreement as to
whether z-scores or percentilesshould be used, especially regarding children
under 2due to their changing body complexion. The most acceptedtool to assess
overweight, obesity and severe obesity is the BodyMass Index (BMI). This document
provides recommendationson how to approach clinical care with affected children.
PMID- 28704024
TI - [Gastroesophageal Reflux Disease Review(GERD)].
AB - GERD is a highly prevalent disease in our country. It has adeep impact in
patient's quality of life, representing extremelyhigh costs regarding health. The
correct understanding ofits pathophysiology is crucial for the rational use of
diagnosesmethods and the implementation of appropriate treatmentadjusted to each
individual case. In this review we evaluatethis disorder based on the best
available evidence, focusingin pathophysiological mechanisms, its epidemiology,
moderndiagnosis methods and current management standards.
PMID- 28704025
TI - Diagnosis and Differential Diagnosis of Cushing's Syndrome.
PMID- 28704026
TI - Diagnosis and Differential Diagnosis of Cushing's Syndrome.
PMID- 28704027
TI - Diagnosis and Differential Diagnosis of Cushing's Syndrome.
PMID- 28704028
TI - Oppositely Charged Polyurethane Microspheres with Tunable Zeta Potentials as an
Injectable Dual-Loaded System for Bone Repair.
AB - To effectively repair irregular shaped bone defects by a minimally invasive
procedure, the exploration of an injectable gel to fill the defect is desirable.
Herein, positively and negatively charged polyurethane microspheres (PU-A and PU
B) with adjustable zeta potentials as well as the hydroxyapatite-loaded PU
microsphere (PU-A/HA) and the dexamethasone-loaded PU microsphere (PU-B/Dex) were
successfully prepared, and the oppositely charged microspheres could self
assemble into injectable gels with 3D structures by a mutually electrostatic
attraction. The self-assembly PU-A/HA+PU-B/Dex gel exhibited a much higher
elastic modulus (about 0.20 MPa) and excellent shear-thinning and self-recovery
behaviors, which would allow the gel to be injected through a fine syringe to
fill the irregular defect. The in vitro and in vivo experiments demonstrated that
the coexistence of HA and Dex in PU-A/HA+PU-B/Dex gel had a synergistic effect on
cell differentiation and accelerating new bone formation, displaying a good
prospect as an injectable gel for bone repair in minimally invasive surgery.
PMID- 28704029
TI - Encapsulation of Single Nanoparticle in Fast-Evaporating Micro-droplets Prevents
Particle Agglomeration in Nanocomposites.
AB - This work describes the use of fast-evaporating micro-droplets to finely disperse
nanoparticles (NPs) in a polymer matrix for the fabrication of nanocomposites.
Agglomeration of particles is a key obstacle for broad applications of
nanocomposites. The classical approach to ensure the dispersibility of NPs is to
modify the surface chemistry of NPs with ligands. The surface properties of NPs
are inevitably altered, however. To overcome the trade-off between dispersibility
and surface-functionality of NPs, we develop a new approach by dispersing NPs in
a volatile solvent, followed by mixing with uncured polymer precursors to form
micro-droplet emulsions. Most of these micro-droplets contain no more than one NP
per drop, and they evaporate rapidly to prevent the agglomeration of NPs during
the polymer curing process. As a proof of concept, we demonstrate the design and
fabrication of TiO2 NP@PDMS nanocomposites for solar fuel generation reactions
with high photocatalytic efficiency and recyclability arising from the fine
dispersion of TiO2. Our simple method eliminates the need for surface
functionalization of NPs. Our approach is applicable to prepare nanocomposites
comprising a wide range of polymers embedded with NPs of different composition,
sizes, and shapes. It has the potential for creating nanocomposites with novel
functions.
PMID- 28704030
TI - Chemistry Is Dead. Long Live Chemistry!
AB - Chemistry, once king of fluorescence microscopy, was usurped by the field of
fluorescent proteins. The increased demands of modern microscopy techniques on
the "photon budget" require better and brighter fluorophores, causing a renewed
interest in synthetic dyes. Here, we review the recent advances in biochemistry,
protein engineering, and organic synthesis that have allowed a triumphant return
of chemical fluorophores to modern biological imaging.
PMID- 28704031
TI - Supported Dendrimer-Encapsulated Metal Clusters: Toward Heterogenizing
Homogeneous Catalysts.
AB - Recyclable catalysts, especially those that display selective reactivity, are
vital for the development of sustainable chemical processes. Among available
catalyst platforms, heterogeneous catalysts are particularly well-disposed toward
separation from the reaction mixture via filtration methods, which renders them
readily recyclable. Furthermore, heterogeneous catalysts offer numerous handles
some without homogeneous analogues-for performance and selectivity optimization.
These handles include nanoparticle size, pore profile of porous supports, surface
ligands and interface with oxide supports, and flow rate through a solid catalyst
bed. Despite these available handles, however, conventional heterogeneous
catalysts are themselves often structurally heterogeneous compared to homogeneous
catalysts, which complicates efforts to optimize and expand the scope of their
reactivity and selectivity. Ongoing efforts in our laboratories are aimed to
address the above challenge by heterogenizing homogeneous catalysts, which can be
defined as the modification of homogeneous catalysts to render them in a
separable (solid) phase from the starting materials and products. Specifically,
we grow the small nanoclusters in dendrimers, a class of uniform polymers with
the connectivity of fractal trees and generally radial symmetry. Thanks to their
dense multivalency, shape persistence, and structural uniformity, dendrimers have
proven to be versatile scaffolds for the synthesis and stabilization of small
nanoclusters. Then these dendrimer-encapsulated metal clusters (DEMCs) are
adsorbed onto mesoporous silica. Through this method, we have achieved selective
transformations that had been challenging to accomplish in a heterogeneous
setting, e.g., pi-bond activation and aldol reactions. Extensive investigation
into the catalytic systems under reaction conditions allowed us to correlate the
structural features (e.g., oxidation states) of the catalysts and their activity.
Moreover, we have demonstrated that supported DEMCs are also excellent catalysts
for typical heterogeneous reactions, including hydrogenation and alkane
isomerization. Critically, these investigations also confirmed that the supported
DEMCs are heterogeneous and stable against leaching. Catalysts optimization is
achieved through the modulation of various parameters. The clusters are oxidized
(e.g., with PhICl2) or reduced (e.g., with H2) in situ. Changing the dendrimer
properties (e.g., generation, terminal functional groups) is analogous to ligand
modification in homogeneous catalysts, which affect both catalytic activity and
selectivity. Similarly, pore size of the support is another factor in determining
product distribution. In a flow reactor, the flow rate is adjusted to control the
residence time of the starting material and intermediates, and thus the final
product selectivity. Our approach to heterogeneous catalysis affords various
advantages: (1) the catalyst system can tap into the reactivity typical to
homogeneous catalysts, which conventional heterogeneous catalysts could not
achieve; (2) unlike most homogeneous catalysts with comparable performance, the
heterogenized homogeneous catalysts can be recycled; (3) improved activity or
selectivity compared to conventional homogeneous catalysts is possible because of
uniquely heterogeneous parameters for optimization. In this Account, we will
briefly introduce metal clusters and describe the synthesis and characterizations
of supported DEMCs. We will present the catalysis studies of supported DEMCs in
both the batch and flow modes. Lastly, we will summarize the current state of
heterogenizing homogeneous catalysis and provide future directions for this area
of research.
PMID- 28704032
TI - Transparent, Flexible Strain Sensor Based on a Solution-Processed Carbon Nanotube
Network.
AB - The demands for transparent, flexible electronic devices are continuously
increasing due to their potential applications to the human body. In particular,
skin-like, transparent, flexible strain sensors have been developed to realize
multifunctional human-machine interfaces. Here, we report a sandwich-like
structured strain sensor with excellent optical transparency based on highly
purified, solution-processed, 99% metallic CNT-polydimethylsiloxane (PDMS)
composite thin films. Our CNT-PDMS composite strain sensors are mechanically
compliant, physically robust, and easily fabricated. The fabricated strain
sensors exhibit a high optical transparency of over 92% in the visible range with
acceptable sensing performances in terms of sensitivity, hysteresis, linearity,
and drift. We also found that the sensitivity and linearity of the strain sensors
can be controlled by the number of CNT sprays; hence, our sensor can be applied
and controlled based on the need of individual applications. Finally, we
investigated the detections of human activities and emotions by mounting our
transparent strain sensor on various spots of human skins.
PMID- 28704033
TI - Are Women Scientists Getting the Credit They Deserve?
PMID- 28704034
TI - Unique Thermal Stability of Unnatural Hydrophobic Ds Bases in Double-Stranded
DNAs.
AB - Genetic alphabet expansion technology, the introduction of unnatural bases or
base pairs into replicable DNA, has rapidly advanced as a new synthetic biology
area. A hydrophobic unnatural base pair between 7-(2-thienyl)imidazo[4,5
b]pyridine (Ds) and 2-nitro-4-propynylpyrrole (Px) exhibited high fidelity as a
third base pair in PCR. SELEX methods using the Ds-Px pair enabled high-affinity
DNA aptamer generation, and introducing a few Ds bases into DNA aptamers
extremely augmented their affinities and selectivities to target proteins. Here,
to further scrutinize the functions of this highly hydrophobic Ds base, the
thermal stabilities of double-stranded DNAs (dsDNA) containing a noncognate Ds-Ds
or G-Ds pair were examined. The thermal stability of the Ds-Ds self-pair was as
high as that of the natural G-C pair, and apart from the generally higher
stability of the G-C pair than that of the A-T pair, most of the 5'-pyrimidine-Ds
purine-3' sequences, such as CDsA and TDsA, exhibited higher stability than the
5'-purine-Ds-pyrimidine-3' sequences, such as GDsC and ADsC, in dsDNAs. This
trait enabled the GC-content-independent control of the thermal stability of the
designed dsDNA fragments. The melting temperatures of dsDNA fragments containing
the Ds-Ds pair can be predicted from the nearest-neighbor parameters including
the Ds base. In addition, the noncognate G-Ds pair can efficiently distinguish
its neighboring cognate natural base pairs from noncognate pairs. We demonstrated
that real-time PCR using primers containing Ds accurately detected a single
nucleotide mismatch in target DNAs. These unique properties of the Ds base that
affect the stabilities of the neighboring base pairs could impart new functions
to DNA molecules and technologies.
PMID- 28704035
TI - Oblique Colloidal Lithography for the Fabrication of Nonconcentric Features.
AB - Herein, we describe the development of oblique colloidal lithography (OCL) and
establish a systematic patterning strategy for creating libraries of nanosized
nonconcentric plasmonic structures. This strategy combines OCL, capillary force
lithography, and several wet and ion etching steps. Hexagonal arrays of
nonconcentric gold features were created on glass substrates with highly
controllable geometric parameters. The size, geometry, and eccentricity of the
gold features could be independently tuned by controlling the experimental
conditions. Gaps within surface elements could be shrunk to as small as 30 nm,
while the total patterned area was about l cm2. The goal was to devise a method
that offers a high degree of control over the resolution and morphology of
asymmetric structures without the need to resort to electron beam lithography.
This technique also enabled the development of numerous surface patterns through
the stepwise fabrication of separate elements. Complex features, including dots
surrounded nonconcentric targets, nonconcentric hexagram-disks, and nonconcentric
annular aperture arrays, were demonstrated, and their optical properties were
characterized. Indeed, spectroscopic studies and FDTD simulations demonstrated
that Fano resonances could readily be generated by the nonconcentric gold
features. Consequently, our patterning strategy should enable the high-throughput
investigation of plasmonic coupling and Fano resonances as a function of the
physical parameters of the elements within the nanopattern array.
PMID- 28704036
TI - Optical Surface Tension Measurement of Two-Dimensionally Confined Liquid
Surfaces.
AB - Surface tension measurement based on spontaneous capillary wave resonance in
confined micrometer-sized liquid interfaces was demonstrated. A single-beam quasi
elastic laser scattering method was used to detect the resonance. Characteristic
resonant modes were observed on a 44-MUm-sized circular water surface. The
frequencies of the peaks agreed well with those simulated by assuming planar
resonance, and the relationship was further confirmed for triangular, square, and
pentagonal water surfaces. Then, the applicability of the method was successfully
demonstrated by surface tension measurements of aqueous solutions of sodium
dodecyl sulfate. The sensitive detection of capillary resonance opens new
possibilities for the chemical and biochemical analysis of liquid interfaces.
PMID- 28704037
TI - A Single Outer-Sphere Mutation Stabilizes apo-Mn Superoxide Dismutase by 35
degrees C and Disfavors Mn Binding.
AB - The catalytic active site of Mn-specific superoxide dismutase (MnSOD) is
organized around a redox-active Mn ion. The most highly conserved difference
between MnSODs and the homologous FeSODs is the origin of a Gln in the second
coordination sphere. In MnSODs it derives from the C-terminal domain whereas in
FeSODs it derives from the N-terminal domain, yet its side chain occupies almost
superimposable positions in the active sites of these two types of SODs. Mutation
of this Gln69 to Glu in Escherichia coli FeSOD increased the Fe3+/2+ reduction
midpoint potential by >0.6 V without disrupting the structure or Fe binding [
Yikilmaz, E., Rodgers, D. W., and Miller, A.-F. ( 2006 ) Biochemistry 45 ( 4 ),
1151 - 1161 ]. We now describe the analogous Q146E mutant of MnSOD, explaining
its low Mn content in terms increased stability of the apo-Mn protein. In 0.8 M
guanidinium HCl, Q146E-apoMnSOD displays an apparent melting midpoint temperature
(Tm) 35 degrees C higher that of wild-type (WT) apoMnSOD, whereas the Tm of WT
holoMnSOD is only 20 degrees C higher than that of WT-apoMnSOD. In contrast, the
Tm attributed to Q146E-holoMnSOD is 40 degrees C lower than that of Q146E
apoMnSOD. Thus, our data refute the notion that the WT residues optimize the
structural stability of the protein and instead are consistent with conservation
on the basis of enzyme function and therefore ability to bind metal ion. We
propose that the WT-MnSOD protein conserves a destabilizing amino acid at
position 146 as part of a strategy to favor metal ion binding.
PMID- 28704038
TI - Eosinophilic Meningitis Caused by Angiostrongylus cantonensis.
AB - Rat lungworm, Angiostrongylus cantonensis, is one major cause of human
eosinophilic meningitis. This helminth is endemic in Southeast Asia, Pacific
Islands, and the Caribbean and has recently expanded to South America. The
infection is characterized by an elevated eosinophil count in cerebrospinal
fluid. Common symptoms and signs include headache, neck stiffness, paresthesia
and nausea/vomiting. The unique history of eating freshwater and land snails or
slugs within 2 weeks before onset is helpful for diagnosis. Antihelminthic agents
have not shown efficacy in human infection; treatment involves supportive care
with management of inflammation and intracranial pressure.
PMID- 28704039
TI - Symmetry Breaking in Side Chains Leading to Mixed Orientations and Improved
Charge Transport in Isoindigo-alt-Bithiophene Based Polymer Thin Films.
AB - The selection of side chains is important in design of conjugated polymers. It
not only affects their intrinsic physical properties, but also has an impact on
thin film morphologies. Recent reports suggested that a face-on/edge-on bimodal
orientation observed in polymer thin films may be responsible for a three
dimensional (3D) charge transport and leads to dramatically improved mobility in
donor-acceptor based conjugated polymers. To achieve a bimodal orientation in
thin films has been seldom explored from the aspect of molecular design. Here, we
demonstrate a design strategy involving the use of asymmetric side chains that
enables an isoindigo-based polymer to adopt a distinct bimodal orientation,
confirmed by the grazing incidence X-ray diffraction. As a result, the polymer
presents an average high mobility of 3.8 +/- 0.7 cm2 V-1 s-1 with a maximum value
of 5.1 cm2 V-1 s-1, in comparison with 0.47 and 0.51 cm2 V-1 s-1 obtained from
the two reference polymers. This study exemplifies a new strategy to develop the
next generation polymers through understanding the property-structure
relationship.
PMID- 28704040
TI - Uniaxially Stretched Flexible Surface Plasmon Resonance Film for Versatile
Surface Enhanced Raman Scattering Diagnostics.
AB - Surface-enhanced Raman scattering (SERS) spectroscopy affords a rapid, highly
sensitive, and nondestructive approach for label-free and fingerprint diagnosis
of a wide range of chemicals. It is of great significance to develop large-area,
uniform, and environmentally friendly SERS substrates for in situ identification
of analytes on complex topological surfaces. In this work, we demonstrate a
biodegradable flexible SERS film via irreversibly and longitudinally stretching
metal deposited biocompatible poly(epsilon-caprolactone) film. This composite
film after stretching shows surprising phenomena: three-dimensional and periodic
wave-shaped microribbons array embedded with a high density of nanogaps
functioning as hot-spots at an average gap size of 20 nm and nanogrooves array
along the stretching direction. The stretched polymer surface plasmon resonance
film gives rise to more than 10 times signal enhancement in comparison with that
of the unstretched composite film. Furthermore, the SERS signals with high
uniformity exhibit good temperature stability. The polymer SPR film with
excellent flexibility and transparency can be conformally attached onto arbitrary
nonplanar surfaces for in situ detection of various chemicals. Our results pave a
new way for next-generation flexible SERS detection means, as well as enabling
its huge potentials toward green wearable devices for point-of-care diagnostics.
PMID- 28704041
TI - Geometrical Structures of Gas Phase Chromium Oxide Cluster Anions Studied by Ion
Mobility Mass Spectrometry.
AB - Structural assignments of gas phase chromium oxide cluster anions, CrmOn- (m = 1
7), have been achieved by comparison between experimental collision cross
sections measured by ion mobility mass spectrometry and theoretical collision
cross sections of optimized structures by quantum chemical calculations. In the
mass spectrum, significant magic behavior between the numbers m and n was not
observed for CrmOn-, while wide ranges of compositions were observed around
CrmO2m+2- to (CrO3)m- as reported previously. The (CrO3)m- (m = 3-7) ions were
assigned to have monocyclic-ring structures for m = 3-5 and bicyclic rings for m
= 6 and 7. In addition, gradual structural change from these cyclic structures of
(CrO3)m- to three-dimensional structures of CrmO2m+2- was found for m = 4-7. The
energy levels of molecular orbitals of a calculated monocyclic structure of
Cr5O15- were also found to be consistent with previous results of photoelectron
spectroscopy, although those of the bicyclic isomer exhibited a different
behavior. Moreover, the observation of abundant ions generated by collision
induced dissociations at the inlet of the ion drift cell indicates that the
larger sized (CrO3)m- (m > 5) series were unstable and easily dissociated to
smaller ions.
PMID- 28704042
TI - Semicrystalline Polymer Binary-Phase Structure Templated Quasi-Block Graft
Copolymers.
AB - Herein, we report a simple strategy to synthesize quasi-block graft copolymers
using the binary phase structure of semicrystalline polymers as the template. An
unsaturated ionic liquid, 1-vinyl-3-butylimidazolium bis
(trifluoromethylsulfonyl) imide ([VBIm] [TFSI]), is thermodynamically miscible
with poly(vinylidene fluoride-co-hexafluoropropylene) (P(VDF-co-HFP)) in
solution. The solidification of P(VDF-co-HFP)/[VBIm] [TFSI] blend leads to the
expelling of ILs from the crystalline region and the ILs are only located in the
amorphous region. The electron-beam irradiation (EBI) at the solid state of the
blends results in the locally grafting of the ILs onto the polymer blocks in the
amorphous region, while the EBI does not affect the chemical structure of the
crystalline region. Therefore, the quasi-block graft copolymers were achieved
with IL-grafted blocks segregated by the unmodified blocks. The achieved block
copolymers can be microphase separated into the various nanostructures, as the
block copolymers with well-defined structure, upon varying the grafting ratios.
The microphase separated quasi-block grafted copolymers exhibit excellent
mechanical properties and good electrical properties. The elongation at break is
480% and the stress at break is as high as 30 MPa for the sample with the
lamellar-like structure having the grafting ratio of 45.4 wt%.
PMID- 28704043
TI - Structural Insights into Thioether Bond Formation in the Biosynthesis of
Sactipeptides.
AB - Sactipeptides are ribosomally synthesized peptides that contain a characteristic
thioether bridge (sactionine bond) that is installed posttranslationally and is
absolutely required for their antibiotic activity. Sactipeptide biosynthesis
requires a unique family of radical SAM enzymes, which contain multiple [4Fe-4S]
clusters, to form the requisite thioether bridge between a cysteine and the alpha
carbon of an opposing amino acid through radical-based chemistry. Here we present
the structure of the sactionine bond-forming enzyme CteB, from Clostridium
thermocellum ATCC 27405, with both SAM and an N-terminal fragment of its peptidyl
substrate at 2.04 A resolution. CteB has the (beta/alpha)6-TIM barrel fold that
is characteristic of radical SAM enzymes, as well as a C-terminal SPASM domain
that contains two auxiliary [4Fe-4S] clusters. Importantly, one [4Fe-4S] cluster
in the SPASM domain exhibits an open coordination site in absence of peptide
substrate, which is coordinated by a peptidyl-cysteine residue in the bound
state. The crystal structure of CteB also reveals an accessory N-terminal domain
that has high structural similarity to a recently discovered motif present in
several enzymes that act on ribosomally synthesized and post-translationally
modified peptides (RiPPs), known as a RiPP precursor peptide recognition element
(RRE). This crystal structure is the first of a sactionine bond forming enzyme
and sheds light on structures and mechanisms of other members of this class such
as AlbA or ThnB.
PMID- 28704044
TI - New Scandium Borylimido Chemistry: Synthesis, Bonding, and Reactivity.
AB - We report a combined synthetic, mechanistic, and theoretical study of the first
borylimido complex of a rare earth metal, (NacNacNMe2)Sc{NB(NAr'CH)2} (25, Ar' =
2,6-C6H3iPr2, NacNacNMe2 = Ar'NC(Me)CHC(Me)NCH2CH2NMe2). Thermolysis of the
methyl-borylamide (NacNacNMe2)Sc(Me){NHB(NAr'CH)2} (18) generated transient imide
25 via rate-determining, first-order methane elimination (KIE ~ 8.7). In the
absence of external substrate, 25 underwent a reversible cyclometalation reaction
(sp3 C-H bond addition to Sc?Nimide) with a methyl group of the NacNacNMe2 ligand
forming {MeC(NC6H3iPrCH(Me)CH2)CHC(Me)NCH2CH2NMe2}Sc{NHB(NAr'CH)2} (21). In the
presence of pyridine or DMAP, reversible sp2 C-H bond activation occurred,
forming orthometalated complexes (NacNacNMe2)Sc{NHB(NAr'CH)2}(eta2-4-NC5H3R) (R =
H or NMe2). In situ reaction of 25 with HCCTol gives irreversible sp C-H bond
activation under kinetic control, and with MeCCPh [2+2] cycloaddition to
Sc?Nimide takes place. These reactions represent the first substrate activation
processes for any metal-bound borylimide. The bonding in 25 and the mechanism and
thermodynamics of the reactions have been studied using density functional theory
(DFT), supported by quantum theory of atoms in molecules and natural bond orbital
analysis. Although the borylimido and arylimido dianions studied here are
formally isoelectronic and possess comparable frontier molecular orbitals, the
borylimido ligand is both a better pi-donor and sigma-donor, forming stronger and
shorter metal-nitrogen bonds with somewhat reduced ionicity. Despite this,
reactions of these types of borylimides with C-H or C=C bonds are all more
exothermic and more strongly activating than for the corresponding arylimides.
DFT calculations on model systems of differing steric bulk unpicked the
underlying thermodynamic factors controlling the reactions of 25 and its reaction
partners, and a detailed comparison was made with the previously described
arylimido homologues.
PMID- 28704045
TI - Local Environment of Terbium(III) Ions in Layered Nanocrystalline Zirconium(IV)
Phosphonate-Phosphate Ion Exchange Materials.
AB - The structures of Zr(IV) phosphonate-phosphate based, unconventional metal
organic framework materials have been determined using atomic pair distribution
function analysis of high energy, X-ray total scattering diffraction data. They
are found to form as nanocrystalline layers of Zr phosphate, similar to the bulk,
but with a high degree of interlayer disorder and intermediate intralayer order
extending around 5 nm. These materials are of interest for their high selectivity
for 3+ lanthanide ions. To investigate the mechanism of the selectivity, we
utilize difference pair distribution function analysis to extract the local
structural environment of Tb3+ ions loaded into the framework. The ions are found
to sit between the layers in a manner resembling the local environment of Tb in
Scheelite-type terbium phosphate. By mapping this local structure onto that of
the refined structure for zirconium-phenyl-phosphonate, we show how dangling
oxygens from the phosphate groups, acting like nose hairs, are able to reorient
to provide a friendly intercalation environment for the Tb3+ ions.
PMID- 28704046
TI - Creating a More Perennial Problem? Mountaintop Removal Coal Mining Enhances and
Sustains Saline Baseflows of Appalachian Watersheds.
AB - Mountaintop removal coal mining (MTM) is a form of surface mining where ridges
and mountain tops are removed with explosives to access underlying coal seams.
The crushed rock material is subsequently deposited in headwater valley fills
(VF). We examined how this added water storage potential affects streamflow using
a paired watershed approach consisting of two sets of mined and unmined
watersheds in West Virginia. The mined watersheds exported 7-11% more water than
the reference watersheds, primarily due to higher and more sustained baseflows.
The mined watersheds exported only ~1/3 of their streamflow during storms, while
the reference watersheds exported ~2/3 of their annual water yield during runoff
events. Mined watersheds with valley fills appear to store precipitation for
considerable periods of time and steadily export this alkaline and saline water
even during the dry periods of the year. As a result, MTMVFs in a mixed
mined/unmined watershed contributed disproportionately to streamflow during
baseflow periods (up to >90% of flow). Because MTMVFs have both elevated summer
baseflows and continuously high concentrations of total dissolved solids, their
regional impact on water quantity and quality will be most extreme and most
widespread during low flow periods.
PMID- 28704047
TI - CuI-Catalyzed Fluorodesulfurization for the Synthesis of Monofluoromethyl Aryl
Ethers.
AB - An efficient CuI-catalyzed fluorodesulfurization for the synthesis of
monofluoromethyl aryl ethers using DAST at room temperature has been developed.
This approach exhibits a good functional group tolerance, a broad substrate
scope, and a high synthesis efficiency.
PMID- 28704048
TI - Band Gap Tuning via Lattice Contraction and Octahedral Tilting in Perovskite
Materials for Photovoltaics.
AB - Tin and lead iodide perovskite semiconductors of the composition AMX3, where M is
a metal and X is a halide, are leading candidates for high efficiency low cost
tandem photovoltaics, in part because they have band gaps that can be tuned over
a wide range by compositional substitution. We experimentally identify two
competing mechanisms through which the A-site cation influences the band gap of
3D metal halide perovskites. Using a smaller A-site cation can distort the
perovskite lattice in two distinct ways: by tilting the MX6 octahedra or by
simply contracting the lattice isotropically. The former effect tends to raise
the band gap, while the latter tends to decrease it. Lead iodide perovskites show
an increase in band gap upon partial substitution of the larger formamidinium
with the smaller cesium, due to octahedral tilting. Perovskites based on tin,
which is slightly smaller than lead, show the opposite trend: they show no
octahedral tilting upon Cs-substitution but only a contraction of the lattice,
leading to progressive reduction of the band gap. We outline a strategy to
systematically tune the band gap and valence and conduction band positions of
metal halide perovskites through control of the cation composition. Using this
strategy, we demonstrate solar cells that harvest light in the infrared up to
1040 nm, reaching a stabilized power conversion efficiency of 17.8%, showing
promise for improvements of the bottom cell of all-perovskite tandem solar cells.
The mechanisms of cation-based band gap tuning we describe are broadly applicable
to 3D metal halide perovskites and will be useful in further development of
perovskite semiconductors for optoelectronic applications.
PMID- 28704049
TI - Phylogenomics of 2,4-Diacetylphloroglucinol-Producing Pseudomonas and Novel
Antiglycation Endophytes from Piper auritum.
AB - 2,4-Diacetylphloroglucinol (DAPG) (1) is a phenolic polyketide produced by some
plant-associated Pseudomonas species, with many biological activities and
ecological functions. Here, we aimed at reconstructing the natural history of
DAPG using phylogenomics focused at its biosynthetic gene cluster or phl genes.
In addition to around 1500 publically available genomes, we obtained and analyzed
the sequences of nine novel Pseudomonas endophytes isolated from the antidiabetic
medicinal plant Piper auritum. We found that 29 organisms belonging to six
Pseudomonas species contain the phl genes at different frequencies depending on
the species. The evolution of the phl genes was then reconstructed, leading to at
least two clades postulated to correlate with the known chemical diversity
surrounding DAPG biosynthesis. Moreover, two of the newly obtained Pseudomonas
endophytes with high antiglycation activity were shown to exert their inhibitory
activity against the formation of advanced glycation end-products via DAPG and
related congeners. Its isomer, 5-hydroxyferulic acid (2), detected during
bioactivity-guided fractionation, together with other DAPG congeners, were found
to enhance the detected inhibitory activity. This report provides evidence of a
link between the evolution and chemical diversity of DAPG and congeners.
PMID- 28704050
TI - Linear, Hypervalent Se34- Units and Unprecedented Cu4Se9 Building Blocks in the
Copper(I) Selenide Ba4Cu8Se13.
AB - Single-crystal and polycrystalline Ba4Cu8Se13 were synthesized; the average
crystal structure was solved by single-crystal X-ray diffraction, and the
structural model was confirmed by a detailed electron microscopy study of
polycrystalline Ba4Cu8Se13. The title compound can be rationalized as
(Ba2+)4(Cu+)8(Se2-)2(Se22-)4(Se34-) and crystallizes in a new structure type
(space group C2/c with a = 9.171(8) A, b = 9.146(8) A, c = 27.35(3) A, beta =
93.21(3) degrees , and V = 2291 A3). It contains unprecedented Cu4Se9 fragments
with planar Cu rectangles. These fragments form two-dimensional layers via
regular (2c-2e) Se-Se bonds. Two of these layers are then connected in the third
dimension via linear, hypervalent Se34- units, resulting in "sandwichlike",
layered building blocks, which are stacked along c and separated by Ba.
Ba4Cu8Se13 is the first example where Se22- and Se34- groups coexist. We were
able to visualize the crystal structure by recording HAADF images, which clearly
reveal the Cu4Se9 fragments and linear Se34- units. The title compound is a
charge-balanced semiconductor and possesses a large Seebeck coefficient (380 MUV
K-1 at 200 K) and a low thermal conductivity (0.77 W m-1 K-1 at 200 K)-two
requirements for efficient thermoelectric materials.
PMID- 28704051
TI - A Combined Theoretical and Experimental Study of Sarin (GB) Decomposition at High
Temperatures.
AB - Theoretical and experimental results are presented for the pyrolytic
decomposition of the nerve agent sarin (GB) in the gas phase. High-level quantum
chemistry calculations are performed together with a semiclassical transition
state theory for describing quantum mechanical tunneling. The experimental and
theoretical results for the temperature dependence of the survival times show
very good agreement, as does the calculated and measured activation energy for
thermal decomposition. The combined results suggest that the thermal
decomposition of GB, for temperature ranging from 350 to 500 degrees C, goes
through a pericyclic reaction mechanism with a transition state consisting of a
six-membered ring structure.
PMID- 28704052
TI - Discovery and Kinetic Profiling of 7-Aryl-1,2,4-triazolo[4,3-a]pyridines:
Positive Allosteric Modulators of the Metabotropic Glutamate Receptor 2.
AB - We report the synthesis and biological evaluation of a series of 7-aryl-1,2,4
triazolo[4,3-a]pyridines with mGlu2 positive allosteric modulator (PAM) activity
and affinity. Besides traditional in vitro parameters of potency and affinity,
kinetic parameters kon, koff and residence time (RT) were determined. The PAMs
showed various kinetic profiles; kon values ranged over 2 orders of magnitude,
whereas RT values were within a 10-fold range. Association rate constant kon was
linearly correlated to affinity. Evaluation of a short, medium, and long RT
compound in a label-free assay indicated a correlation between RT and functional
effect. The effects of long RT compound 9 on sleep-wake states indicated long RT
was translated into sustained inhibition of rapid eye movement (REM) in vivo.
These results show that affinity-only driven selection would have resulted in
mGlu2 PAMs with high values for kon but not necessarily optimized RT, which is
key to predicting optimal efficacy in vivo.
PMID- 28704053
TI - Cobalt Catalysis for Enantioselective Cyclobutanone Construction.
AB - Over the past 40 years, intramolecular hydroacylation has favored five-membered
rings, in preference to four membered rings. Herein, we report a catalyst derived
from earth-abundant cobalt that enables preparation of cyclobutanones, with
excellent regio-, diastereo-, and enantiocontrol, under mild conditions (2 mol %
catalyst loading and as low as 50 degrees C).
PMID- 28704054
TI - Enhanced Systemic Anti-Angiogenic siVEGF Delivery Using PEGylated Oligo-d
arginine.
AB - Angiogenesis mainly mediated by upregulation of vascular endothelial growth
factor (VEGF) provides a hallmark of rapidly proliferating tumor cells and an
essential component of the tumor growth and microenvironment, making it a
targetable process for antitumor therapy. RNA interference (RNAi) provides a very
effective tool for developing antitumor therapies; however, its application to
date has been hampered due to the lack of efficient small interfering RNA (siRNA)
delivery systems in vivo. Here, we report a polymeric gene carrier system based
on PEGylation of a cationic cysteine-ended 9-mer arginine oligopeptide (CR9C),
which provides effective siRNA systemic delivery and specifically suppresses VEGF
(siVEGF). The PEG500-CR9C/siVEGF oligopeptoplex provided improved blood
circulation, enhanced protection from serum proteases, reduced uptake in the
liver and kidneys, enhanced tumor targeting, and down-regulated intratumoral VEGF
level, which comprehensively resulted in improved antitumor efficacy without
significant toxicity in vivo. PEG500-CR9C has a great potential for safe and
efficient siRNA delivery with diverse applications.
PMID- 28704055
TI - Electrochemical Nickel Catalysis for Sp2-Sp3 Cross-Electrophile Coupling
Reactions of Unactivated Alkyl Halides.
AB - A constant-current electrochemical method for reducing catalytic nickel complexes
in sp2-sp3 cross-electrophile coupling reactions has been developed. The
electrochemical reduction provides reliable nickel catalyst activation and
turnover and offers a tunable parameter for reaction optimization, in contrast to
more standard activated metal powder reductants. The electrochemical reactions
give yields (i.e., 51-86%) and selectivities as high or superior to those using
metal powder reductants and provide access to a wider substrate scope.
PMID- 28704056
TI - A Nano-in-Nano Polymer-Dendrimer Nanoparticle-Based Nanosystem for Controlled
Multidrug Delivery.
AB - Codelivery of multiple chemotherapeutics with different action mechanisms is a
promising strategy for cancer treatment. In this study, we developed a novel
polymer-dendrimer hybrid nanoparticle-based nanosystem for efficient and
controlled codelivery of two model chemotherapeutics, doxorubicin (DOX) and
paclitaxel (PTX). The nanosystem was characterized to have a nano-in-nano
structure with a size of around 150 nm. The model drugs could feasibly be loaded
into the nanosystem ratiometrically with high drug-loading contents by
controlling the feeding drug ratios. Also, the model drugs could be released from
the nanosystem following a sequential release manner-specifically, quick PTX
release and sustained DOX release. Acidic pH was found to enhance the release of
both drugs. Moreover, the nanosystem was taken up by cancer cells rapidly and
efficiently, and the delivered drugs could release sustainably and efficiently in
cells to reach their action targets. In vitro cytotoxicity results demonstrated
that, by optimizing drug ratios, the dual-drug-loaded nanosystem could result in
better antitumor efficacy than the single-drug-loaded nanosystem or free dual
drug combination. Furthermore, the dual-drug-loaded nanosystem could induce
significant changes in both the nucleus and tubulin patterns synergistically. All
data suggest that the nano-in-nano polymer-dendrimer hybrid nanoparticle-based
nanosystem is a promising candidate to achieve controlled multidrug delivery for
effective combination cancer therapy.
PMID- 28704057
TI - Peptide Macrocyclization Assisted by Traceless Turn Inducers Derived from Ugi
Peptide Ligation with Cleavable and Resin-Linked Amines.
AB - A multicomponent approach enabling the installation of turn-inducing moieties
that facilitate the macrocyclization of short and medium-size oligopeptides is
described. The strategy comprises the Ugi ligation of peptide carboxylic acids
and isocyanopeptides in the presence of aldehydes and acid or photolabile amines
followed by cyclization and cleavage of the backbone N-substituents to render
canonical cyclopeptides. Implementing the approach on solid phase with the use of
Rink amide resins led to a new class of backbone amide linker strategy.
PMID- 28704058
TI - Elucidating Protein-DNA Interactions in Human Alphoid Chromatin via Hybridization
Capture and Mass Spectrometry.
AB - The centromere is the chromosomal locus where the kinetochore forms and is
critical for ensuring proper segregation of sister chromatids during cell
division. A substantial amount of effort has been devoted to understanding the
characteristic features and roles of the centromere, yet some fundamental aspects
of the centromere, such as the complete list of elements that define it, remain
obscure. It is well-known that human centromeres include a highly repetitive
class of DNA known as alpha satellite, or alphoid, DNA. We present here the first
DNA-centric examination of human protein-alpha satellite interactions, employing
an approach known as HyCCAPP (hybridization capture of chromatin-associated
proteins for proteomics) to identify the protein components of alphoid chromatin
in a human cell line. Using HyCCAPP, cross-linked alpha satellite chromatin was
isolated from cell lysate, and captured proteins were analyzed via mass
spectrometry. After being compared to proteins identified in control pulldown
experiments, 90 proteins were identified as enriched at alphoid DNA. This list
included many known centromere-binding proteins in addition to multiple novel
alpha satellite-binding proteins, such as LRIF1, a heterochromatin-associated
protein. The ability of HyCCAPP to reveal both known as well as novel alphoid DNA
interacting proteins highlights the validity and utility of this approach.
PMID- 28704059
TI - Tuning Li-Ion Diffusion in alpha-LiMn1-xFexPO4 Nanocrystals by Antisite Defects
and Embedded beta-Phase for Advanced Li-Ion Batteries.
AB - Olivine-structured LiMn1-xFexPO4 has become a promising candidate for cathode
materials owing to its higher working voltage of 4.1 V and thus larger energy
density than that of LiFePO4, which has been used for electric vehicles batteries
with the advantage of high safety but disadvantage of low energy density due to
its lower working voltage of 3.4 V. One drawback of LiMn1-xFexPO4 electrode is
its relatively low electronic and Li-ionic conductivity with Li-ion one
dimensional diffusion. Herein, olivine-structured alpha-LiMn0.5Fe0.5PO4
nanocrystals were synthesized with optimized Li-ion diffusion channels in LiMn1
xFexPO4 nanocrystals by inducing high concentrations of Fe2+-Li+ antisite
defects, which showed impressive capacity improvements of approaching 162, 127,
73, and 55 mAh g-1 at 0.1, 10, 50, and 100 C, respectively, and a long-term
cycling stability of maintaining about 74% capacity after 1000 cycles at 10 C. By
using high-resolution transmission electron microscopy imaging and joint
refinement of hard X-ray and neutron powder diffraction patterns, we revealed
that the extraordinary high-rate performance could be achieved by suppressing the
formation of electrochemically inactive phase (beta-LiMn1-xFexPO4, which is first
reported in this work) embedded in alpha-LiMn0.5Fe0.5PO4. Because of the coherent
orientation relationship between beta- and alpha-phases, the beta-phase embedded
would impede the Li+ diffusion along the [100] and/or [001] directions that was
activated by the high density of Fe2+-Li+ antisite (4.24%) in alpha-phase. Thus,
by optimizing concentrations of Fe2+-Li+ antisite defects and suppressing beta
phase-embedded olivine structure, Li-ion diffusion properties in LiMn1-xFexPO4
nanocrystals can be tuned by generating new Li+ tunneling. These findings may
provide insights into the design and generation of other advanced electrode
materials with improved rate performance.
PMID- 28704060
TI - ZnO Nanocrystal Networks Near the Insulator-Metal Transition: Tuning Contact
Radius and Electron Density with Intense Pulsed Light.
AB - Networks of ligand-free semiconductor nanocrystals (NCs) offer a valuable
combination of high carrier mobility and optoelectronic properties tunable via
quantum confinement. In principle, maximizing carrier mobility entails crossing
the insulator-metal transition (IMT), where carriers become delocalized. A recent
theoretical study predicted that this transition occurs at nrho3 ~ 0.3, where n
is the carrier density and rho is the interparticle contact radius. In this work,
we satisfy this criterion in networks of plasma-synthesized ZnO NCs by using
intense pulsed light (IPL) annealing to tune n and rho independently. IPL applied
to as-deposited NCs increases rho by inducing sintering, and IPL applied after
the NCs are coated with Al2O3 by atomic layer deposition increases n by removing
electron-trapping surface hydroxyls. This procedure does not substantially alter
NC size or composition and is potentially applicable to a wide variety of
nanomaterials. As we increase nrho3 to at least twice the predicted critical
value, we observe conductivity scaling consistent with arrival at the critical
region of a continuous quantum phase transition. This allows us to determine the
critical behavior of the dielectric constant and electron localization length at
the IMT. However, our samples remain on the insulating side of the critical
region, which suggests that the critical value of nrho3 may in fact be
significantly higher than 0.3.
PMID- 28704061
TI - Acid-Base Polymeric Foams for the Adsorption of Micro-oil Droplets from
Industrial Effluents.
AB - Separation of toxic organic pollutants from industrial effluents is a great
environmental challenge. Herein, an acid-base engineered foam is employed for
separation of micro-oil droplets from an aqueous solution. In acidic or basic
environments, acid-base polymers acquire surface charge due to protonation or
dissociation of surface active functional groups. This property is invoked to
adsorb crude oil microdroplets from water using polyester polyurethane (PESPU)
foam. The physicochemical surface properties of the foam were characterized using
X-ray photoelectron spectroscopy, inverse gas chromatography, electrokinetic
analysis, and micro-computed tomography. Using the surface charge of the foam and
oil droplets, the solution pH (5.6) for maximum separation efficacy was
predicted. This optimal pH was verified through underwater wetting behavior and
adsorption experiments. The droplet adsorption onto the foam was governed by
physisorption, and the driving forces were attributed to electrostatic attraction
and Lifshitz-van der Waals forces. The foam was regenerated and reused multiple
times by simple compression. The lowest trace oil content in the retentate was
3.6 mg L-1, and all oil droplets larger than 140 nm were removed. This work lays
the foundation for the development of a new class of engineered foam adsorbents
with the potential to revolutionize water treatment technologies.
PMID- 28704062
TI - FlexTouch: An Insulin Pen-Injector with a Low Activation Force Across Different
Insulin Formulations, Needle Technologies, and Temperature Conditions.
AB - FlexTouch(r) (Novo Nordisk A/S, Bagsvaerd, Denmark) is a pen-injector with a
torque spring mechanism requiring a low activation force. This laboratory-based
study compared the activation force of FlexTouch during the injection of insulin
with different needles and at temperature conditions within the range at which
the device is recommended for use. Using a tensile tester, activation force was
measured at maximum dose settings for insulin detemir (100 U/mL) and insulin
degludec (100 and 200 U/mL) at standard (23 degrees C +/- 5 degrees C), cool (5
degrees C +/- 3 degrees C), and warm (30 degrees C +/- 2 degrees C) conditions.
Activation force was measured with two 32-gauge needles differing in internal
diameter at standard conditions. At standard, cool, and warm conditions,
estimated mean activation forces with 95% confidence interval were 5.71 newtons
(N) (5.63-5.79), 5.94 N (5.83-6.06), and 5.69 N (5.58-5.80) with insulin detemir,
5.53 N (5.45-5.62), 5.56 N (5.44-5.67), and 5.33 N (5.22-5.44) with 100 U/mL
insulin degludec, and 5.53 N (5.45-5.61), 5.83 N (5.71-5.94), and 5.56 N (5.45
5.68) with 200 U/mL insulin degludec, respectively. Mean activation forces were
observed to be low with very small variability between measurements; however, the
differences between insulins and temperature conditions were statistically
significant. The activation force required by FlexTouch remained low across all
situations tested. The differences between activation force needed with different
insulins and temperature conditions were small and unlikely to be clinically
meaningful.
PMID- 28704063
TI - Evaluation of Accuracy of Six Blood Glucose Monitoring Systems and Modeling of
Possibly Related Insulin Dosing Errors.
AB - OBJECTIVE: Self-monitoring of blood glucose (BG) is an essential part of diabetes
therapy. Accurate and reliable results from BG monitoring systems (BGMS) are
important especially when they are used to calculate insulin doses. This study
aimed at assessing system accuracy of BGMS and possibly related insulin dosing
errors. RESEARCH DESIGN AND METHODS: System accuracy of six different BGMS (Accu
Chek(r) Aviva Nano, Accu-Chek Mobile, Accu-Chek Performa Nano, CONTOUR(r) NEXT
LINK 2.4, FreeStyle Lite, OneTouch(r) Verio(r) IQ) was assessed in comparison to
a glucose oxidase and a hexokinase method. Study procedures and analysis were
based on ISO 15197:2013/EN ISO 15197:2015, clause 6.3. In addition, insulin
dosing error was modeled. RESULTS: In the comparison against the glucose oxidase
method, five out of six BGMS fulfilled ISO 15197:2013 accuracy criteria. Up to
14.3%/4.3%/0.3% of modeled doses resulted in errors exceeding +/-0.5/+/-1.0/+/
1.5 U and missing the modeled target by 20 mg/dL/40 mg/dL/60 mg/dL, respectively.
Compared against the hexokinase method, five out of six BGMS fulfilled ISO
15197:2013 accuracy criteria. Up to 25.0%/10.5%/3.2% of modeled doses resulted in
errors exceeding +/-0.5/+/-1.0/+/-1.5 U, respectively. CONCLUSIONS: Differences
in system accuracy were found, even among BGMS that fulfilled the minimum system
accuracy criteria of ISO 15197:2013. In the error model, considerable insulin
dosing errors resulted for some of the investigated systems. Diabetes patients on
insulin therapy should be able to rely on their BGMS' readings; therefore, they
require highly accurate BGMS, in particular, when making therapeutic decisions.
PMID- 28704064
TI - Nucleic Acid Extraction from Synthetic Mars Analog Soils for in situ Life
Detection.
AB - Biological informational polymers such as nucleic acids have the potential to
provide unambiguous evidence of life beyond Earth. To this end, we are developing
an automated in situ life-detection instrument that integrates nucleic acid
extraction and nanopore sequencing: the Search for Extra-Terrestrial Genomes
(SETG) instrument. Our goal is to isolate and determine the sequence of nucleic
acids from extant or preserved life on Mars, if, for example, there is common
ancestry to life on Mars and Earth. As is true of metagenomic analysis of
terrestrial environmental samples, the SETG instrument must isolate nucleic acids
from crude samples and then determine the DNA sequence of the unknown nucleic
acids. Our initial DNA extraction experiments resulted in low to undetectable
amounts of DNA due to soil chemistry-dependent soil-DNA interactions, namely
adsorption to mineral surfaces, binding to divalent/trivalent cations,
destruction by iron redox cycling, and acidic conditions. Subsequently, we
developed soil-specific extraction protocols that increase DNA yields through a
combination of desalting, utilization of competitive binders, and promotion of
anaerobic conditions. Our results suggest that a combination of desalting and
utilizing competitive binders may establish a "universal" nucleic acid extraction
protocol suitable for analyzing samples from diverse soils on Mars. Key Words:
Life-detection instruments-Nucleic acids-Mars-Panspermia. Astrobiology 17, 747
760.
PMID- 28704065
TI - Re: Castle, et al., 2017; Diabetes Technol Ther; DOI: 10.1089/dia.2017.0012.
PMID- 28704066
TI - Using a Multidisciplinary Algorithm to Treat Self-Injurious Behavior in a Young
Boy with Developmental Delays.
PMID- 28704067
TI - Grip Type Alters Maximal Pinch Forces in Syringe Use.
AB - OBJECTIVE: The purpose of this study was to determine maximum forces during
syringe use for different grips found in the field. BACKGROUND: Prolonged syringe
use in chemotherapy drug delivery is associated with pain and injury in nurses
and technicians. METHOD: Twenty healthy female hospital workers generated
isometric maximum voluntary force using a 30 cc syringe with four pinch grips
(chuck, chuck variation, thenar, two-handed). Both dominant and nondominant hands
were used with the syringe plunger fixed in wide (8.3 cm) and narrow (2.5 cm)
grip spans. Participants were encouraged to position the apparatus in the most
comfortable position and exert a maximal effort for 5 seconds. RESULTS:
Significant interaction effects were found: Grip Span * Pinch Type, Hand * Pinch
Type, and Grip Span * Hand * Pinch Type ( p < .05). The results demonstrated that
the thenar (103.6 +/- 22.9 N) and two-handed (104.7 +/- 17.1 N) pinches produced
the highest forces. CONCLUSION: Thenar and two-handed pinch grips may be the
preferred pinch type to lower the relative efforts required to use a syringe and
may be one strategy to assist with reduction of musculoskeletal disorder risk
associated with syringe use. APPLICATION: Determining maximal syringe press
forces allows workers and ergonomists to develop better strategies for managing
the cumulative loads during drug delivery and mixing.
PMID- 28704068
TI - Breaking Down Barriers in Pediatric Mental Health Consultations: Understanding
Patients' Use of I DON'T KNOW.
AB - Barriers to effective provider-patient communication take many forms that can be
difficult to recognize and appropriately address. This paper offers probabilistic
indicators for one such form, patient-produced "I don't know" (IDK),
distinguishing its use as a cognitive claim and its use as a strategy for
resisting discussion of sensitive topics. A total of 95 audio-recorded
psychiatrist-child interactions are drawn from a US-wide corpus of physician
patient consultations. From these, 376 patient-produced IDKs are extracted and
coded for linguistic/social factors, including form, function, prosody, age,
gender, and primary diagnosis. Two multiple logistic regressions are performed to
determine the predictors of cognitive and resistive IDK functions respectively.
Cognitive IDK uses are associated with the full form (p < 0.01) and unstressed
prosody (p < 0.01). Use of resistive IDK is correlated with decreasing patient
age (p < 0.01) and emotionally labile mental health diagnoses (p < 0.01).
Cognitive and resistive IDK uses have distinctive linguistic and social
distributions in psychiatrist-child interactions, where cognitive uses have two
objectively identifiable linguistic characteristics and resistive uses are
associated with certain patient types. Providers may learn to recognize cognitive
and resistive IDK uses, thus acquiring the ability to correctly interpret
interactional cues relevant to the diagnosis and treatment of pediatric mental
health conditions.
PMID- 28704069
TI - Potent synchronization of peripheral circadian clocks by glucocorticoid
injections in PER2::LUC-Clock/Clock mice.
AB - In mammals, the central clock (the suprachiasmatic nuclei, SCN) is entrained
mainly by the light-dark cycle, whereas peripheral clocks in the peripheral
tissues are entrained/synchronized by multiple factors, including feeding
patterns and endocrine hormones such as glucocorticoids. Clock-mutant mice
(Clock/Clock), which have a mutation in a core clock gene, show potent phase
resetting in response to light pulses compared with wild-type (WT) mice, owing to
the damped and flexible oscillator in the SCN. However, the phase resetting of
the peripheral clocks in Clock/Clock mice has not been elucidated. Here, we
characterized the peripheral clock gene synchronization in Clock/Clock mice by
daily injections of a synthetic glucocorticoid (dexamethasone, DEX) by monitoring
in vivo PER2::LUCIFERASE bioluminescence. Compared with WT mice, the Clock/Clock
mice showed significantly decreased bioluminescence and peripheral clock rhythms
with decreased amplitudes and delayed phases. In addition, the DEX injections
increased the amplitudes and advanced the phases. In order to examine the
robustness of the internal oscillator, T-cycle experiments involving DEX
stimulations with 24- or 30-h intervals were performed. The Clock/Clock mice
synchronized to the 30-h T-cycle stimulation, which suggested that the peripheral
clocks in the Clock/Clock mice had increased synchronizing ability upon DEX
stimulation, to that of circadian and hour-glass type oscillations, because of
weak internal clock oscillators.
PMID- 28704070
TI - Geographic Variation in Mentally Unhealthy Days: Air Pollution and Altitude
Perspectives.
AB - : Ha, Hoehun. Geographic variation in mentally unhealthy days: air pollution and
altitude perspectives. High Alt Med Biol. 18:258-266, 2017. BACKGROUND: Mental
health incorporates our emotional, psychological, and social well-being and it is
critical at each phase of life, from youth and preadulthood through adulthood.
METHODS: We assessed the association between mentally unhealthy days (MUDs), air
pollutant concentrations, and altitude on the basis of cross-county studies. Data
on poor mental health days for the United States were based on health-related
telephone surveys conducted by the Behavioral Risk Factor Surveillance System
(BRFSS). Average annual regional air pollution data were obtained from Center for
Disease Control and Prevention (CDC) WONDER Environmental data, and altitude data
were collected from the U.S. Geological Survey (USGS). RESULTS: In the data set
(across 2589 U.S. counties for 2011), even after accounting for potential
confounding variables and multicollinearity, a significant association between
altitude, air pollution, and poor mental health days was found, explaining that
poor mental health days increase with increasing air pollution concentrations and
with decreasing altitude (R2 = 0.663, p < 0.001). Controlling for socioeconomic
(e.g., education and employment) and social (including social relationship and
crime) factors did not change these findings. CONCLUSIONS: In this study, we
found that counties with lower air pollution and higher altitude had
significantly lower average number of MUDs reported within the past 30 days. This
association has not been reported before in the literature. These findings
suggest a need for further investigation into the extent that air quality and
altitude may serve as significant factors for mental health and have major
implications in our understanding of the etiology of mental health by medical
professionals.
PMID- 28704072
TI - Effects of Active Videogame and Sports, Play, and Active Recreation for Kids
Physical Education on Children's Health-Related Fitness and Enjoyment.
AB - OBJECTIVE: The purpose of the study was to compare the effects of a Kinect active
videogame (AVG) and the Sports, Play, and Active Recreation for Kids (SPARK)
intervention in improving children's health-related fitness and physical activity
(PA) enjoyment. MATERIALS AND METHODS: A total of 65 students from both third and
fourth grade in a rural elementary school participated in the study. The third
graders (N = 29, mean age = 9.1 years, 10 boys, mean body mass index [BMI] =
20.1) were assigned to a SPARK physical education group, while the fourth graders
(N = 36, mean age = 10.2 years, 15 boys, mean BMI = 20.3) were enrolled in the
Kinect AVG group. The intervention lasted for 6 weeks, with each week including
three practice sessions (~40 minutes per session). All participants were measured
on their health-related fitness by testing their performance in the 15-m
Progressive Aerobic Cardiovascular Endurance Run (PACER), curl-ups, and push-ups
both before and after the interventions. Participants' PA enjoyment was measured
immediately after the first and last session's practice. Various ANCOVA tests
were conducted to analyze the intervention effects on the changes of health
related fitness performances and enjoyment while controlling for baseline values,
gender, and BMI. Various MANOVA tests were used to examine the intervention
effects on PA levels during three practice sessions. RESULTS: Participants in AVG
group had greater improvement in 15-m PACER test (P < 0.001), as well as PA
enjoyment (P < 0.05), than those in SPARK group. The AVG group generated higher
light PA and lower sedentary time for three (P < 0.05 to P < 0.001) and two
sessions (P < 0.05 and P < 0.001), respectively. In addition, the AVG group
accumulated higher moderate-to-vigorous physical activity (MVPA) for the first
session (P < 0.01), while the SPARK group generated higher MVPA for the third
session (P < 0.001). No MVPA difference was found between groups for another
session. CONCLUSION: A 6-week (40 minutes * 3 times/week) program using AVG could
be an effective strategy in improving children's cardiorespiratory fitness while
maintaining PA enjoyment.
PMID- 28704073
TI - Transformative Possibilities: Politics and Cosmetic Surgery in the Bolivarian
Revolution.
AB - I examine the intersection of politics and aesthetics in a public hospital in
Caracas, Venezuela in the first years of the twenty-first century. Given
Venezuela's long-standing embrace of physical enhancement and the contradictions
of the medical values of cosmetic surgery with those of Bolivarian socialism, the
changing surgical practices at a well-established public site offer a significant
case for considering how different actors negotiate the dialectics of care. In
the face of increasing resource shortages, negotiations of aesthetic care
contributed to tensions in the clinical encounter as patients creatively pushed
Bolivarian policies to support their pursuits of aesthetic self-improvement.
PMID- 28704071
TI - Social Monogamy in Nonhuman Primates: Phylogeny, Phenotype, and Physiology.
AB - Monogamy as a social system has been both a scientific puzzle and a sociocultural
issue for decades. In this review, we examine social monogamy from a comparative
perspective with a focus on primates, our closest genetic relatives. We break
down monogamy into component elements, including pair-bonding and partner
preference, mate guarding or jealousy, social attachment, and biparental care.
Our survey of primates shows that not all features are present in species
classified as socially monogamous, in the same way that human monogamous
relationships may not include all elements-a perspective we refer to as "monogamy
a la carte." Our review includes a survey of the neurobiological correlates of
social monogamy in primates, exploring unique or common pathways for the
elemental components of monogamy. This compilation reveals that the components of
monogamy are modulated by a suite of androgenic steroids, glucocorticoid
hormones, the nonapeptide hormones oxytocin and vasopressin, and other
neurotransmitter systems (e.g., dopamine and opioids). We propose that efforts to
understand the biological underpinnings of complex human and animal sociosexual
relationships will be well served by exploring individual phenotypic traits, as
opposed to pursuing these questions with the assumption that monogamy is a
unitary trait or a species-specific characteristic.
PMID- 28704074
TI - Quantifying the relative importance to patients of avoiding symptoms and outcomes
of heart failure.
AB - OBJECTIVE: To evaluate heart failure (HF) patients' disease knowledge and
preferences for avoiding different disease outcomes. METHODS: An online survey
was administered to 400 individuals with a self-reported diagnosis of HF to
elicit relative importance weights (RIWs) for avoiding 11 potential HF symptoms
and outcomes using best-worst scaling. The survey also included questions about
individuals' HF knowledge, and demographic and disease-experience
characteristics. Differences in RIWs among sub-groups, defined by HF knowledge,
caregiver support, age, recent hospitalization or emergency room visit for HF,
health-related quality-of-life, and cardiac device experience were examined.
RESULTS: Relative to limitations in usual activities (RIW 1.00), respondents
preferred avoiding severe, infrequent cardiovascular events (e.g. stroke [RIW
8.51], heart transplant [RIW 7.84], or heart attack [RIW 5.3]) most, followed by
difficulty breathing (RIW 2.55), inability to enjoy life (RIW 1.84), cardiac
device implantation (RIW 1.74), and atrial fibrillation (RIW 1.57). Patients
preferred avoiding swelling (RIW 0.47) and fatigue (RIW 0.58) least. RIWs for
avoiding severe, infrequent events were higher among those with high disease
knowledge, those without caregivers, and those without a recent hospitalization
or emergency room visit. CONCLUSIONS: Patients' preferences for avoiding HF
outcomes vary across outcomes and by individuals' knowledge, caregiver status,
and age. Healthcare providers should solicit and incorporate insights about
patients' knowledge of HF and their preferences for avoiding HF outcomes into HF
education and management planning efforts.
PMID- 28704075
TI - Arecoline cannot alter testicular dysfunction and pineal activation caused by
noise in wistar rat.
AB - Millions of people consume betel nut for increased capacity to work and for
stress reduction. The nut contains arecoline, which has multiple side effects on
endocrine functions. Objective of the work is to investigate pineal-testicular
responses to noise and after arecoline treatment in noise in rats. Noise exposure
(100 dB, 6 h daily, 10 days) caused pineal stimulation ultrastructurally and at
indoleamines level. Leydig cell dysfunction with fall of testosterone level and
suppression of sex accessories were noticed. In contrast, pineal activity was
inhibited and reproductive functions were stimulated after arecoline
administration, confirmed from reversed changes to those of noise. Arecoline
treatment in noise exposure showed same results as in noise both in pineal and in
reproductive functions. It is concluded that noise causes testicular dysfunction
probably by gonadotropin suppression induced by pineal melatonin in noise.
Furthermore, arecoline cannot prevent it in noise in rats.
PMID- 28704076
TI - Providing high-quality care for patients with liver disease.
PMID- 28704077
TI - The assessment and care of patients with hepatic encephalopathy.
AB - This article provides an overview of the metabolic brain dysfunction hepatic
encephalopathy (HE). HE is caused by severe liver cirrhosis and patients will
often be treated in a liver unit, but patients with symptoms of HE may require
nursing care anywhere in the healthcare system. Therefore it is beneficial for
all nurses to have a basic knowledge of HE and this article explains the symptoms
and treatment. Possible differential diagnoses are presented, as well as factors
that can trigger episodes of HE. Both patients' and relatives' experiences are
examined. Finally, the nurse's role in caring for patients with HE is described,
along with the dilemmas and challenges involved.
PMID- 28704078
TI - Domestic violence protection measures.
AB - In this article Richard Griffith, Senior Lecturer in Health Law at Swansea
University, sets out the powers available to the police and court to protect
people from domestic violence.
PMID- 28704079
TI - Paediatric inter-hospital transportation: a clinical governance project.
AB - This article discusses a quality improvement project in the context of paediatric
inter-hospital transportation. The project was set in a large university teaching
hospital in Ireland. Risk assessment on the clinical site revealed a gap in the
application of best national and international standards in inter-hospital
transportation practice. A project was undertaken to explore current paediatric
transport services and respond to a clinical service deficit. Consequently, the
proposed quality improvement initiative proposes a universal Paediatric Advanced
Life Support Programme (PALS) to upskill and enhance the required clinical
standards and competencies of neonatal nurses. This intervention was underpinned
by attention to change management principles and organisational culture in health
care. As a clinical practice development, it demonstrates how benchmarking
against best practice can advance the quality and safety agenda in paediatric
practice. Education initiatives are recommended to ensure that clinical standards
in paediatric transportation are monitored and reviewed with the potential to
improve clinical outcomes.
PMID- 28704080
TI - The pay cap must go.
PMID- 28704081
TI - BJN Awards: Hepatology and Liver Nurse of the Year Runner up 2017.
PMID- 28704082
TI - You can never be too 'care-full'.
AB - In her second blog in the series, Clare Price-Dowd, Senior Programme Lead, NHS
Leadership Academy, Leeds, talks about the importance of care in nurses' day-to
day lives, both for patients and colleagues.
PMID- 28704083
TI - Online opinions changing care.
PMID- 28704084
TI - The impact on patients of a nurse-led clinical service in gastroenterology.
AB - Higher rates of chronic liver disease have resulted in a significant increase in
the number of patients needing regular abdominal paracentesis for ascites.
Waiting times for admission at the Royal Wolverhampton NHS Trust had become
longer and delays in intervention and treatment became inevitable. In 2014, the
Trust developed a nurse-led abdominal paracentesis day-case service. A
qualitative evaluation of the service was conducted using in-depth patient
interviews and surveys to determine the impact of the service, including how the
new nursing role affected the patient experience. The results show that the nurse
led clinical service in gastroenterology positively impacts patients'
experiences. Following this innovation, the service was extended to provide
intravenous infusions for gastroenterology patients via the day-case unit. With
appropriate training and competency assessments, nurses can now perform selected
medical procedures safely and effectively, thereby facilitating nursing staff to
expand and develop their roles. This development has substantial implications for
nursing and is an important contribution to the debate on the future direction of
the nursing profession.
PMID- 28704085
TI - World Health Organization: providing global leadership for patient safety.
AB - John Tingle, Reader in Health Law at Nottingham Trent University, discusses a
recent publication from the World Health Organization on making health care
safer.
PMID- 28704086
TI - Making effective use of dashboards.
AB - Sam Foster, Chief Nurse at Heart of England NHS Foundation Trust, considers some
of the pitfalls users might encounter when collating and interpreting data.
PMID- 28704087
TI - Resilience as part of nursing education: supporting nurses in times of austerity.
AB - Janet Scammell, Associate Professor (Nursing), Bournemouth University, discusses
the challenging environment nurses are working in and the role of resilience in
creating a sustainable NHS workforce.
PMID- 28704088
TI - The development of Lymphoedema Network Wales to improve care.
AB - Lymphoedema Network Wales was developed in 2011, after receiving a L1 million
recurring investment from the Welsh Government to implement its Lymphoedema
Strategy. This article describes the creation of the network and the importance
of capturing performance data. It will also provide information on the three
programmes of work, covering service development, education and research, and
innovations and technology. Within Wales, the focus of lymphoedema service
delivery is on 'prudent health care', working with patients for patients and only
doing what is necessary to gain a good result. Centring our service on evidence
based practice is vital to ensure achievable patient outcomes. The network has
grown considerably over the past 6 years and is recognised as a forward-thinking
and proactive service.
PMID- 28704089
TI - Malaria: diagnosis, treatment and management of a critically ill patient.
AB - Malaria is a significant cause of mortality in many countries and remains the
most prevalent parasitic tropical infection. The World Health Organization
estimates that 50% of the world's population is at risk of malaria, with most
deaths occurring in sub-Saharan Africa. This case study explores the management
of a malaria patient admitted to a critical care unit in Zambia, a lower-middle
income country in sub-Saharan Africa. While malaria is prevalent in Zambia and
other countries, in the UK all malaria is imported and less frequently seen by
health professionals. This case study will raise the profile of malaria,
including its recognition, diagnosis and treatment. This information will assist
nurses in both low- and high-income countries to translate theory into practice
and improve nurses' understanding of a condition rarely seen in UK critical care
practice.
PMID- 28704090
TI - Cortrak tube placement part 1: confirming by quadrant may be unsafe.
AB - Gastric confirmation by pH is only achievable in approximately 50% of placements
and X-rays are expensive and may be misinterpreted. Bedside electromagnetic (EM)
guidance offers real-time confirmation. The authors determined the accuracy of
guidance in predicting gastric body position from the EM trace using official
Cortrak guidance (the EM trace reaches the bottom left quadrant of the anterior
screen) compared with local guidance (detailed anterior-depth description of the
GI flexures). X-ray, pH or an EM trace beyond the gastric body were used to
independently confirm gastric position. Of 496 EM traces, 49% of tubes were in
the oesophagus on entry to the lower left quadrant whereas 12% had already
reached the gastric body in the upper left quadrant. Overall, predicting position
by quadrant was 70% accurate whereas differentiating the pre-gastro-oesophageal
junction (pre-GOJ) from the gastric body flexure was 100% accurate. Confirming
gastric position by the anterior trace quadrant appears to be unsafe whereas
expert differentiation of the pre-GOJ and gastric body flexures was reliable. The
authors invite Corpak Medsystems (now owned by Halyard Health) to update its
guidance in view of these findings.
PMID- 28704091
TI - Revalidation reflection: a military nursing research perspective.
AB - Lt Cdr Alan Brockie, Lecturer, Medical Directorate, Academic Department of
Military Nursing, Birmingham.
PMID- 28704092
TI - NMC consultation on proficiencies to be met for registration.
AB - Emeritus Professor Alan Glasper, from the University of Southampton, discusses
the Nursing and Midwifery Council's public consultation on the efficacy of its
new draft standards for pre-registration nursing education.
PMID- 28704093
TI - How Are Fathers' Demographic Characteristics Related to Preschool-Age Children's
Weight and Obesity Risk Factors?
AB - Fathers (n = 149) of preschool children were interviewed using the Child Feeding,
Role of the Father (ROF), and ROF at Mealtimes (ROFM) questionnaires to determine
whether fathers' demographic characteristics are associated with child
overweight. Low-income was associated with higher pressure to eat (p = .006) and
perceived their child as higher weight (p = .001). Higher education level was
associated with lower ROF (p = .018) and ROFM (p = .002) and higher child diet
quality (p = .002). Father's BMI was positively associated with ROFM (p = .008).
Certain fathers may be important targets in childhood obesity prevention
programs.
PMID- 28704094
TI - TAKOTSUBO-LIKE CARDIOMYOPATHY IN A LARGE COHORT OF PATIENTS WITH PHEOCHROMOCYTOMA
AND PARAGANGLIOMA.
AB - OBJECTIVE: Pheochromocytoma (PHEO) and paraganglioma (PGL) (PPGL) may cause acute
Takotsubo-like catecholamine cardiomyopathy (TLC). The objective of this study
was to determine the prevalence and clinical presentation of TLC in a large
cohort of patients with PPGL. METHODS: We reviewed retrospectively the records of
consecutive patients with PPGL investigated in our center from 1995 to 2016. We
collected clinical and paraclinical data of patients that had TLC in this cohort.
We performed a literature review of cases of Takotsubo cardiomyopathy related to
PPGL described between 1990 and 2015. RESULTS: Our cohort included 275 patients
with PPGL. Acute TLC was found in 4 of 152 (2.6%) patients with secreting PPGL.
There was no event recorded in 123 patients with unknown presurgical secretion (n
= 51) or nonsecreting PPGL (n = 72). Four patients (44 to 79 years old) fulfilled
the criteria for TLC, including 2 PHEO and 2 PGL patients. A precipitating
stressor event was identified in 3 cases including surgery (n = 2) and upper
respiratory tract infection. In all cases, the diagnosis of PPGL came after the
cardiac event and following the investigation of a lesion incidentally found at
imaging. Moreover, we identified in the literature 59 cases described in the last
25 years and analyzed this cohort together with our 4 new cases. CONCLUSION:
Acute TLC may be found in up to 3% of patients with secreting PPGL. Considering
that the diagnosis of PPGL was performed following incidental finding of
radiologic mass, the real prevalence of PPGL in TTC remains to be determined.
ABBREVIATIONS: ECG = electrocardiogram; LVEF = left ventricular ejection
fraction; MIBG = metaiodobenzylguanidine; PGL = paraganglioma; PHEO =
pheochromocytoma; PPGL = pheochromocytoma and paraganglioma; TLC = Takotsubo-like
cardiomyopathy; TTC = Takotsubo cardiomyopathy; ULN = upper limit of normal.
PMID- 28704095
TI - SARCOPENIA: AN ENDOCRINE DISORDER?
AB - : Sarcopenia is defined as low muscle function (walking speed or grip strength)
in the presence of low muscle mass. A simple screening test-the SARC-F-is
available to identify persons with sarcopenia. The major endocrine causes of
sarcopenia are diabetes mellitus and male hypogonadism. Other causes are
decreased physical activity, loss of motor neuron units, weight loss,
inflammatory cytokines, reduced blood flow to muscles, very low 25(OH) vitamin D
levels, and decreased growth hormone and insulin-like growth factor 1. Treatment
for sarcopenia includes resistance and aerobic exercise, leucine-enriched
essential amino acids, and vitamin D. In hypogonadal males, testosterone improves
muscle mass, strength, and function. Selective androgen receptor molecules and
anti-myostatin activin II receptor molecules are under development as possible
treatments for sarcopenia. ABBREVIATIONS: COPD = chronic obstructive pulmonary
disease DHEA = dehydroepiandrosterone IGF-1 = insulin-like growth factor 1 GH =
growth hormone mTOR = mammalian target of rapamycin SARM = selective androgen
receptor molecule.
PMID- 28704096
TI - EPIDEMIOLOGY OF GASTROINTESTINAL NEUROENDOCRINE TUMORS IN A U.S. COMMERCIALLY
INSURED POPULATION.
AB - OBJECTIVE: To estimate incidence and prevalence of gastrointestinal
neuroendocrine tumors (GI NETs) in U.S. commercially insured patients. METHODS:
This was a retrospective, cross-sectional study using 2009 to 2014 data from
MarketScan and PharMetrics commercial claims databases. Patients were 18 to 64
years old, and had 1 inpatient or 2 outpatient claims with GI NET, identified by
International Classification of Diseases, 9th Revision, Clinical Modification
codes. Incidence was calculated as number of patients with NET who were disease
free for 2 years prior, divided by number of enrollees and reported as per
million person-years (PMPY). Prevalence was calculated as the number of GI NET
patients divided by the number of enrollees per year. RESULTS: The annual number
of patients with GI NET ranged from 2,014 to 3,413 in MarketScan and 1,436 to
2,336 in PharMetrics. Incidence increased from 2011 to 2014: 67.0 to 79.1 PMPY in
MarketScan and 47.4 to 58.2 PMPY in PharMetrics. Incidence increased by 24.3% in
females and 10.7% in males in MarketScan, and by 17.6% in females and 29.3% in
males in PharMetrics. Incidence increased with age and was highest in the 45 to
54 and 55 to 64 age groups. Prevalence increased from 77.9 to 131.2 per million
per year (MarketScan) and 50.8 to 108.9 (PharMetrics) from 2009 to 2014.
Prevalence was generally higher in females than males and highest in 55 to 64
year olds. These increases may be due to better diagnostics, increased awareness
of NET among clinicians and pathologists, and/or actual increase in disease.
CONCLUSION: Clinicians may see GI NET with increasing frequency and should become
more familiar with its presentation and treatment. ABBREVIATIONS: GI =
gastrointestinal; ICD-9-CM = International Classification of Diseases, 9th
Revision, Clinical Modification; NET = neuroendocrine tumor; PMPY = per million
person-years; SEER = Surveillance, Epidemiology, and End Results.
PMID- 28704097
TI - MANAGING THYROID TUMORS DIAGNOSED AS NON-INVASIVE FOLLICULAR TUMOR WITH PAPILLARY
LIKE NUCLEAR FEATURES (NIFTP).
AB - This commentary summarizes the history and reclassification of noninvasive
follicular thyroid tumor with papillary like nuclei (NIFTP). The salient
histopathologic features, which are based on immunohistochemical and molecular
profiles and serve as inclusion and exclusion criteria are reviewed. The authors
also provide their own point of view regarding the practical issues and possible
concerns that may be raised by both clinicians and patients based on the
diagnosis of NIFTP.
PMID- 28704098
TI - ACCURACY OF PLASMA FREE METANEPHRINES IN THE DIAGNOSIS OF PHEOCHROMOCYTOMA AND
PARAGANGLIOMA: A SYSTEMATIC REVIEW AND META-ANALYSIS.
AB - OBJECTIVE: Various studies have validated plasma free metanephrines (MNs) as
biomarkers for pheochromocytoma and paraganglioma (PPGL). This meta-analysis
aimed to estimate the overall diagnostic accuracy of this biochemical test for
PPGL. METHODS: We searched the PubMed, the Cochrane Library, Web of Science,
Embase, Scopus, OvidSP, and ProQuest Dissertations & Theses databases from
January 1, 1995 to December 2, 2016 and selected studies written in English that
assessed plasma free MNs in the diagnosis of PPGL. Quality Assessment of
Diagnostic Accuracy Studies 2 (QUADAS-2) was used to evaluate the quality of the
included studies. We calculated pooled sensitivities, specificities, positive and
negative likelihood ratios, diagnostic odds ratios (DORs) and areas under curve
(AUCs) with their 95% confidence intervals (95% CIs). Heterogeneity was assessed
by I2. To identify the source of heterogeneity, we evaluated the threshold effect
and performed a meta-regression. Deeks' funnel plot was selected for
investigating any potential publication bias. RESULTS: Although the combination
of metanephrine (MN) and normetanephrine (NMN) carried lower specificity (0.94,
95% CI 0.90-0.97) than NMN (0.97, 95% CI 0.92-0.99), NMN was generally more
accurate than individual tests, with the highest AUC (0.99, 95% CI 0.97-0.99),
DOR (443.35, 95% CI 216.9-906.23), and pooled sensitivity (0.97, 95% CI 0.94
0.98) values. Threshold effect and meta-regression analyses showed that different
cut-offs, blood sampling positions, study types and test methods contributed to
heterogeneity. CONCLUSION: This meta-analysis suggested an effective value for
combined plasma free MNs for the diagnosis of PPGL, but testing for MNs requires
more standardization using tightly regulated studies. ABBREVIATIONS: AUC = area
under curve; CI = confidence interval; DOR = diagnostic odds ratio; EIA = enzyme
immunoassay; LC-ECD = liquid chromatography-electrochemical detection; LC-MS/MS =
liquid chromatography-tandem mass spectrometry; MN = metanephrine; NMN =
normetaneprhine; PPGL = pheochromocytoma and paraganglioma; QUADAS-2 = Quality
Assessment of Diagnostic Accuracy Studies 2.
PMID- 28704099
TI - LONG-TERM OUTCOMES AND PROGNOSTIC FACTORS IN PATIENTS WITH DIFFERENTIATED THYROID
CANCER AND DISTANT METASTASES.
AB - OBJECTIVE: Distant metastatic spread is the most frequent cause of thyroid cancer
related death. The objective of this study was to evaluate overall and disease
related survival of patients with differentiated thyroid cancer (DTC) and distant
metastases (DM) attending a single medical center and to investigate variables
predictive of better long-term outcomes. METHODS: The Rabin Medical Center
Thyroid Cancer Registry was searched for patients with DM from DTC. RESULTS: The
cohort included 138 patients (58.7% female) diagnosed at age 54.7 +/- 19.5 years.
Mean primary tumor size was 33.9 +/- 26 mm. Most patients (57.7%) were stage
T3/T4; 48.7% had extrathyroidal extension; 53.5% had lymph node metastases.
Histopathology yielded papillary and follicular thyroid carcinoma in 66.7% and
13.8%, respectively, and intermediate/poorly differentiated carcinoma in 19.6%.
All but 2 patients underwent total thyroidectomy, and 133/138 (96.4%) received
radioactive iodine (RAI) therapy. DM were synchronous in 55.1%. The mean follow
up was 8.2 years from detection of metastases. The common sites of metastases
were the lungs (85.6% of patients), bones (39.9%), brain (5.8%) and liver (3.6%).
At last follow-up, resolution was documented in 24.6% of patients,
improvement/stable disease in 31.6%, and structurally progressive disease in
43.4%. By the end of the study, 40.6% of patients died, 23.2% of DTC. Improved
overall survival and disease progression were associated with younger age, lung
only DM, and metastatic RAI avidity. CONCLUSION: Patients with DTC and DM treated
by standard-of-care approaches frequently achieve favorable long-term outcomes.
Novel therapies might be necessary in only a minority of these patients, and the
reported prognostic factors can aid in their identification. ABBREVIATIONS: CR =
complete response; DM = distant metastases; DTC = differentiated thyroid cancer;
ETE = extra-thyroidal extension; M0 = detected during follow-up; M1 = detected at
diagnosis; MSKCC = Memorial Sloan Kettering Cancer Center; NED = no evidence of
disease; OS = overall survival; PFS = progression free survival; PTC = papillary
thyroid cancer; RAI = radioactive iodine; Tg = thyroglobulin.
PMID- 28704100
TI - THE ENDOCRINOLOGY OF AGING: A KEY TO LONGEVITY "GREAT EXPECTATIONS".
AB - ABBREVIATIONS: AMP = adenosine monophosphate CETP = cholesteryl ester transfer
protein FOXO = Forkhead box O GH = growth hormone HDL = high-density lipoprotein
IGF-1 = insulin-like growth factor 1 LDL = low-density lipoprotein miRNA =
microRNA mTOR = mammalian target of rapamycin SIRT = sirtuin T4 = thyroxine TSH =
thyroid-stimulating hormone "The Moving Finger writes; and, having writ, Moves
on: nor all thy Piety nor Wit Shall lure it back to cancel half a Line, Nor all
thy Tears wash out a Word of it." Omar Khayyam ( 1 ).
PMID- 28704101
TI - AGING, DIABETES, AND FALLS.
AB - KEY POINTS Falls are a major health issue for older adults, leading to adverse
events and even death. Older persons with type 2 diabetes are at increased risk
of falling compared to healthy adults of a similar age. Over 400 factors are
associated with falls risk, making identification and targeting of key factors to
prevent falls problematic. However, the major risk factors include hypertension,
diabetes, pain, and polypharmacy. In addition to age and polypharmacy, diabetes
related loss of strength, sensory perception, and balance secondary to peripheral
neuropathy along with decline in cognitive function lead to increased risk of
falling. Designing specific interventions to target strength and balance
training, reducing polypharmacy to improve cognitive function, relaxation of
diabetes management to avoid hypoglycemia and hypotension, and relief of pain
will produce the greatest benefit for reducing falls in older persons with
diabetes. Abbreviation: DPN = diabetic polyneuropathy.
PMID- 28704102
TI - UPDATE ON THE BIOLOGY OF OSTEOCALCIN.
AB - : A genetics approach has uncovered that bone has more functions than expected.
In particular, bone is an endocrine organ that secretes a growing number of
hormones. In that context, the discovery of the osteoblast-derived hormone
osteocalcin has significantly broadened the field of bone biology because of the
number of physiologic processes regulated by this hormone. At present,
osteocalcin has been shown to enhance several aspects of energy metabolism, brain
development, and cognition. These discoveries shed light on the cross-talk
between multiple organs and provide credence to the search for additional
endocrine functions of bone. ABBREVIATIONS: ECM = extracellular matrix; Gprc6a =
G protein-coupled receptor family C group 6 member A; IL-6 = interleukin-6; WT =
wild-type.
PMID- 28704103
TI - POSTPRANDIAL DOSING OF BOLUS INSULIN IN PATIENTS WITH TYPE 1 DIABETES: A CROSS
SECTIONAL STUDY USING DATA FROM THE T1D EXCHANGE REGISTRY.
AB - OBJECTIVE: To assess the prevalence and characteristics of patients with type 1
diabetes (T1D) who dose bolus insulin postprandial (PostP) versus preprandial
(PreP). METHODS: Data for this cross-sectional study were obtained from 21,533
participants in the T1D Exchange Registry. Data were drawn from the enrollment
questionnaire. Patients who dosed 'immediately before meal' or 'several minutes
before meal' were classified as PreP. Patients who dosed 'during meal' or 'after
meal' were classified as PostP. Data reported (PostP vs. PreP) are mean +/- SD
and percentage, as appropriate. RESULTS: After exclusion of patients who did not
answer the dose-timing question or who selected 'not given regularly' or 'depends
on glucose level prior to meal,' (4,229 of 25,762), 21,533 patients were included
in the study. Ninety-nine percent of patients used rapid-acting insulin
analogues; 32% dosed insulin PostP. Compared to PreP, children <18 years of age
dosing PostP were characterized by higher glycated hemoglobin (HbA1c) (8.7 +/-
1.5% [72 +/- 16.4 mmol/mol] vs. 8.4 +/- 1.7% [68 +/- 18.6 mmol/mol]), larger
insulin dose (1.2 +/- 0.7 IU/kg/day vs. 1.1 +/- 0.7 IU/kg/day), greater
prevalence of history of hypoglycemia, and diabetic ketoacidosis. Adults who
dosed PostP were characterized by younger age (33.0 +/- 15.3 years vs. 39.5 +/-
16.6 years), higher HbA1c (8.3 +/- 1.5% [67 +/- 16.4 mmol/mol] vs. 7.8 +/- 1.5%
[62 +/- 16.4 mmol/mol]), and larger insulin dose (1.0 +/- 0.6 IU/kg/day vs. 0.9
+/- 0.5 IU/kg/day) than PreP. CONCLUSION: This study reveals that a large
proportion of patients dose bolus insulin PostP. Despite the use of current rapid
acting insulin analogues, patients who dose PostP are characterized by poorer
glycemic control in all patients and a greater prevalence of history of severe
hypoglycemia and diabetic ketoacidosis in children. ABBREVIATIONS: BMI = body
mass index; CGM = continuous glucose monitoring; DKA = diabetic ketoacidosis;
HbA1c = glycated hemoglobin; PostP = postprandial; PreP = preprandial; SMBG =
self-monitored blood glucose; T1D = type 1 diabetes.
PMID- 28704105
TI - Role of the Polymorphisms of Uncoupling Protein Genes in Childhood Obesity and
Their Association with Obesity-Related Disturbances.
AB - BACKGROUND: Obesity, one of the most common disorders observed in clinical
practice, has been associated with energy metabolism-related protein genes such
as uncoupling proteins (UCPs). Herein, we evaluated UCPs as candidate genes for
obesity and its morbidities. METHODS: A total of 268 obese and 185 nonobese
children and adolescents were enrolled in this study. To determine dyslipidemia,
hypertension, and insulin resistance, laboratory tests were derived from fasting
blood samples. UCP1-3826 A/G, UCP2 exon 8 deletion/insertion (del/ins), and UCP3
55C/T variants were also genotyped, and the relationships among the polymorphisms
of these UCPs and obesity morbidities were investigated. RESULTS: The mean ages
of the obese and control groups were 11.61 +/- 2.83 and 10.74 +/- 3.36 years,
respectively. The respective genotypic frequencies of the AA, AG, and GG
genotypes of UCP1 were 46.3%, 33.2%, and 20.5% in obese subjects and 46.5%,
42.2%, and 11.4% in the controls (p = 0.020). G alleles were more frequent in
obese subjects with hypertriglyceridemia (42.9%; p = 0.048) than in those
without, and the GG genotype presented an odds ratio for obesity of 2.02 (1.17
3.47; p = 0.010). The polymorphisms of UCP2 exon 8 del/ins and UCP3-55C/T did not
influence obesity risk (p > 0.05). The I (ins) allele was associated with low HDL
cholesterolemia (p = 0.023). CONCLUSION: The GG genotype of the UCP1-3826 A/G
polymorphism appears to contribute to the onset of childhood obesity in Turkish
children. The GG genotype of UCP1, together with the del/del genotype of the UCP2
polymorphism, may increase the risk of obesity with synergistic effects. The ins
allele of the UCP2 exon 8 del/ins polymorphism may contribute to low HDL
cholesterolemia.
PMID- 28704106
TI - Prescription Drug Misuse and Arrest History.
AB - BACKGROUND: Prescription drug misuse is widely acknowledged as a major public
health issue in the United States. Surprisingly little research examines the
association between prescription drug misuse and history of arrest among adults.
METHODS: We use data from the 2013 National Survey on Drug Use and Health to
examine this association. Arrest was self-reported and separated into three
categories: any, property crime, or violent crime. Prescription drug misuse was
defined as use without a prescription or solely for the feeling or experience
caused by the drug. We looked at the misuse of any prescription drug and also
separate classes of misuse (pain relievers, sedatives, tranquilizers, and
stimulants). Several multivariate logistic regression models were estimated to
examine the association between prescription drug misuse and arrest. RESULTS:
Findings showed that 8.62% of respondents reported prescription drug misuse and
3.55% reported any arrest. In multivariate models that included demographic
characteristics and measures of alcohol and other drug use, respondents who
reported prescription drug misuse were at increased odds of arrest. CONCLUSIONS:
The current research shows that prescription drug misuse is significantly
associated with arrest, but more research is needed on the causal nature of this
association. The criminal justice and drug treatment systems must develop
treatment and rehabilitation services that understand the close association
between prescription drug misuse and arrest.
PMID- 28704107
TI - Asthma medication use among adults with current asthma by work-related asthma
status, Asthma Call-back Survey, 29 states, 2012-2013.
AB - OBJECTIVE: Asthma severity is defined as the intensity of treatment required to
achieve good control of asthma symptoms. Studies have shown that work-related
asthma (WRA) can be associated with poorer asthma control and more severe
symptoms than non-WRA. Associations between asthma medications and WRA status
were assessed using data from the 2012-2013 Asthma Call-back Survey among ever
employed adults (>=18 years) with current asthma from 29 states. METHODS: Persons
with WRA had been told by a physician that their asthma was work-related. Persons
with possible WRA had asthma caused or made worse by their current or previous
job, but did not have physician-diagnosed WRA. Asthma medications were classified
as controller (i.e., long-acting beta-agonist, inhaled corticosteroid, oral
corticosteroid, cromolyn/nedocromil, leukotriene pathway inhibitor,
methylxanthine, anti-cholinergics) and rescue (i.e., short-acting beta-agonist).
Demographic and clinical characteristics were examined. Associations between
asthma medications and WRA status were assessed using a multivariate logistic
regression to calculate adjusted prevalence ratios (PRs). RESULTS: Among an
estimated 15 million ever-employed adults with current asthma, 14.7% had WRA and
an additional 40.4% had possible WRA. Compared with adults with non-WRA, those
with WRA were more likely to have taken anti-cholinergics (PR = 1.80),
leukotriene pathway inhibitor (PR = 1.59), and methylxanthine (PR = 4.76), and
those with possible WRA were more likely to have taken methylxanthine (PR =
2.85). CONCLUSIONS: Results provide additional evidence of a higher proportion of
severe asthma among adults with WRA compared to non-WRA. To achieve optimal
asthma control, adults with WRA may require additional intervention, such as
environmental controls or removal from the workplace exposure.
PMID- 28704108
TI - Reliability of kinetic visual field testing in children with mutation-proven
retinal dystrophies: Implications for therapeutic clinical trials.
AB - PURPOSE: Kinetic visual field testing is used to monitor disease course in
retinal dystrophy clinical care and treatment response in treatment trials, which
are increasingly recruiting children. This study investigates Goldmann visual
field (GVF) changes in young children with mutation-proven retinal dystrophies as
they age and with progression of the retinal degeneration. METHODS: Retrospective
review of children <= 17 years old with a mutation-proven retinal dystrophy.
Objective clinical disease activity was assessed by a retinal degeneration
specialist masked to GVF results. Digital quantification of GVF area was
performed. RESULTS: Twenty-nine children (58 eyes), ages 5-16, were identified.
GVF area increased with age despite progression in 20 children and clinical
stability in nine children. Mean +/- standard error increase in GVF area/year was
333 +/- 130 mm2 (I4e, p = 0.012), 720 +/- 155 mm2 (III4e, p < 0.001), and 759 +/-
167 mm2 (IV4e, p < 0.001), with greater increases at earlier ages. Repeatability
coefficients were 7381 mm2 (I4e), 9379 mm2 (III4e), and 10346 mm2 (IV4e),
indicating a large variability. At 2.5 years after the baseline GVF the area
increased >= 20%, the criterion for positive treatment outcome defined in recent
published therapeutic trials, in 38% (I4e), 34% (III4e), and 33% (IV4e) of eyes.
CONCLUSION: In a substantial proportion of children with mutation-proven retinal
dystrophies, there is a significant increase in GVF area with age, particularly
those < 12 years, despite progression or stability of disease. These findings
suggest that change in GVF area in children with retinal dystrophies can be an
unreliable measure of response to treatment and on which to base appropriate
counseling about visual impairment.
PMID- 28704109
TI - Heterogeneity in Drinking Practices in England and Wales and Its Association With
Violent Behavior: A Latent Class Analysis.
AB - BACKGROUND: Crude single-item consumption metrics, such as "binge drinking"
measures, mask the complexity and heterogeneity in young people's drinking; thus
limiting our understanding of young people's drinking patterns as well as how
alcohol drinking is associated with violent outcomes. OBJECTIVES: The current
study employed a range of consumption and contextual indicators to explore
heterogeneity in young people's (16-29 years) drinking practices, giving due
consideration to their social nature. It also assessed to what extent
heterogeneity in drinking practices was associated with violent outcomes.
METHODS: Employing data from the 2006 Offending Crime and Justice Survey, three
measures of alcohol consumption and nine drinking context indicators were
utilized within latent class analysis to create typologies of drinking practices
among current drinkers in England and Wales (n = 2711) and examine their
association with violent outcomes. The validity of the typologies was also
assessed on age, sex, and socio-economic status. RESULTS: Three discernible
drinking profiles were identified: "regular social drinkers" (48%), "regular pub
binge drinkers" (32%), and "moderate drinkers" (20%). The "regular pub binge
drinkers" were found to be more than twice as likely to commit an assault offence
(odds ratio = 2.8 95% CI [1.3, 6.2]) when compared to "moderate drinkers" and
"regular social drinkers" (odds ratio = 2.2 95% CI [1.4, 3.4]). CONCLUSIONS:
Interventions aimed at reducing alcohol-related violence ought to give due
consideration to the social context of drinking as well as levels of consumption.
PMID- 28704110
TI - Challenges of managing retinal dystrophies: An experience from south India.
PMID- 28704111
TI - Incomplete dabigatran reversal with idarucizumab.
AB - CONTEXT: With increasing use of direct oral anticoagulants (DOACs), urgent
reversal of these agents becomes a growing concern. Idarucizumab is a humanized
monoclonal antibody fragment that specifically binds to dabigatran with higher
affinity than thrombin, rapidly neutralizing its anticoagulant effect without
increased risk of thrombosis. CASE DETAILS: We describe two cases in which the
recommended dose of idarucizumab was unsuccessful in completely reversing the
anticoagulant effects of dabigatran. Both of these patients were noted to have
supratherapeutic international normalized ratios (INRs) and high dabigatran
concentrations. In the first case, an 86-year-old male underwent an emergent
procedure and experienced excessive hemorrhaging refractory to blood product
repletion, idarucizumab, and factor eight inhibitor bypass activity (FEIBA). In
the second case, a 62-year-old female in shock was found to have elevated
dabigatran concentrations despite two doses of idarucizumab, continuous renal
replacement therapy (CRRT), blood product repletion, and FEIBA. Both patients
ultimately expired from their coagulopathies. DISCUSSION: These cases illustrate
the potential for incomplete reversal of dabigatran with the recommended 5 g of
idarucizumab and emphasize the importance of early detection of dabigatran
toxicity. While direct dabigatran serum concentrations are not readily available,
the INR may be a useful surrogate marker for supratherapeutic dabigatran
concentrations.
PMID- 28704112
TI - The Migration, Mental Stress, and Tobacco use of Internal Migrants in China: The
Moderating Effect of the Social Context of the Host Society.
AB - BACKGROUND: Previous studies on the relationship between mental stress and the
tobacco use of internal migrants have not fully considered the social context of
the host society. OBJECTIVES: This study aims to examine how mental stress
influences cigarette smoking in internal migrants in China by considering the
social context of the host society. METHODS: We used the RUMiC data that were
collected in 15 cities distributed throughout 9 provinces of China. A total of
8,446 and 5,426 migrant workers were interviewed in 2008 and 2009, respectively.
We selected individuals based on the criteria of age, salary, and hukou status. A
total of 8,880 observations are valid for this study. This research used the
logistic regression method to test the association between mental stress and the
tobacco use of internal migrants. RESULTS: The results show that mental stress is
not necessarily associated with the tobacco use of internal migrants. However,
the effects of mental stress on tobacco use are moderated by the social context
of the host society. CONCLUSIONS: This article calls for more attention to be
paid to the moderate effect of social context in the host society on the
association between mental stress and cigarette smoking of internal migrants.
Moreover, this article underscores the importance of factors related to local
societies in making and enacting tobacco control policies for migrants in
developing countries.
PMID- 28704113
TI - Role of resveratrol in the management of insulin resistance and related
conditions: Mechanism of action.
AB - Resveratrol (RES), a well-known antioxidant, is present in numerous plant species
and, as a result, is easily obtained through dietary intake of plant-based foods
and beverages. Several studies suggest that RES has anti-carcinogenic, anti
microbial, and anti-viral effects. It may also have beneficial metabolic
properties that result in mitigation of insulin resistance (IR) and related
metabolic abnormalities, including dyslipidemia, hyperglycemia, and
hyperinsulinemia through regulation of gene expression or the activity of rate
limiting enzymes. A large body of evidence supports the beneficial effects of RES
in the management and treatment of IR, type 2 diabetes, and related complications
through a multitude of mechanisms. This review article focuses on the mechanisms
of action of RES, the mechanisms leading to improved insulin sensitivity, and its
clinical role in the management and treatment of type 2 diabetes.
PMID- 28704114
TI - Orbital floor fracture with entrapment: Imaging and clinical correlations in 45
cases.
AB - Orbital floor fractures (OFF) with entrapment require prompt clinical and
radiographic recognition for timely surgical correction. Correct CT radiographic
interpretation of entrapped fractures can be subtle and thus missed. We reviewed
the clinical, radiographic and intraoperative findings of 45 cases of entrapped
OFF to correlate pre- and intraoperative findings with radiography. Retrospective
review and statistical analysis of 45 patients with OFF using the chi squared and
Kruskal-Wallis tests. Main outcome measures included patient demographics,
clinical features, radiologic interpretation, intraoperative findings, and
treatment outcomes. Twenty-one cases (47%) had radiologic evaluations of orbital
CT scans that included commentary on possible entrapment. Intraoperatively, 16
(76%) of these patients had the inferior rectus muscle incarcerated in the
fracture, while 5 (24%) patients had incarceration of the orbital fat.
Possibility of entrapment was not commented on in the radiology reports of the
remaining 24 (53%) cases. Intraoperatively, 13 (54%) of these patients had the
inferior rectus muscle incarcerated in the fracture, while 11 (46%) patients had
incarceration of the orbital fat. It is vital to assess the possibility of
entrapment, especially in young patients, in the setting of OFF as a delay in
diagnosis may lead to persistent diplopia, disfigurement, or bradycardia. Most
radiology reports did not mention the possibility of entrapment in this cohort. A
key concept is that entrapment occurs when any orbital tissue (muscle or fat) is
trapped in the fracture site.
PMID- 28704115
TI - Trends of Youth Marijuana Treatment Admissions: Increasing Admissions Contrasted
with Decreasing Drug Involvement.
AB - BACKGROUND: Recent changes in marijuana policies and their potential negative
effects on youth development are a public health concern. Identifying the most
appropriate treatment approaches for problematic marijuana use is important.
OBJECTIVES: The aim of this study was to track marijuana use among young people
by examining national changes from 1995 to 2012 in the demographics, referral
sources, and the substance use patterns related to youth admissions to substance
abuse treatment programs. METHODS: We examined first-time substance abuse
treatment admissions among youth, utilizing the Treatment Episode Data Set -
Admissions (TEDS-A) of the Substance Abuse Mental Health Services Administration
(N = 12,025,787). Chi-squared analysis was used to examine differences between
admission years and binomial logistic regression was used to examine trends over
the 18 years. RESULTS: We found increasing numbers of youth in dependent living
situations (e.g. with parents) admitted to substance use disorder treatment for
marijuana. We also found a dramatic drop in the degree of drug involvement for
those admissions over nearly two decades of data. Conclusions/Importance: While
availability and changing perceptions of marijuana might have caused an increase
in admissions to substance abuse treatment, our findings indicate that the
severity of drug use involved in those admissions has decreased. This study
highlights the importance of identifying youth in actual need of treatment
services and not overlooking tools such as screening, brief intervention, and
motivational interviewing as effective for varying levels of marijuana use by
youth.
PMID- 28704117
TI - Climacteric Commentaries.
PMID- 28704116
TI - Popular Views on Addictions and on Prospects for Recovery in Poland.
AB - BACKGROUND: Popular views of addictive substances and behaviors constitute an
important research topic because these views have an impact upon the functioning
of treatment systems and societal responses to substance use disorders. METHODS:
The analysis is based on a random sample of N = 1000 telephone interviews
collected in Poland in 2013. Questionnaire measures targeted such issues as the
perceived risks of addictions and beliefs about potential recovery from various
types of addictions. RESULTS: First, a coherent view of the addiction potential
of various addictive substances and/or behaviors emerges, distinguishing licit
drugs and types of behavior from illicit drugs. Second, treatment optimism proves
to be quite high independent of the type of addictive behavior, while chances of
recovery without treatment are considered less likely. Third, chances for
assisted change (change with treatment) and self-change are considered largely
independent of perceived addiction-related risks and are not perceived as
contradictory. CONCLUSIONS: The results point to the persistence of the disease
model of addiction in Poland, placing responsibility for addiction on the
individual and pairing it with the expectation of undergoing specialized
treatment. This individualistic approach was applied as a framework for addiction
problems in the 1950s to deflect from the shortcomings of the ''new socialist
society.'' Neo-liberal market reform and socioeconomic changes have provided
reinforcement for this individualistic framework.
PMID- 28704118
TI - Gratitude and Drug Misuse: Role of Coping as Mediator.
AB - BACKGROUND: Positive emotions, such as gratitude has been found to be beneficial
to both physical and mental well-being but so far, drug misuse research has yet
to identify important emotive predictors related to drug use. OBJECTIVES: This
study aimed to examine the relationship between gratitude and drug use among a
group of drug misusers. It was hypothesized that greater dispositional gratitude
was associated with lesser drug use through greater use of adaptive coping
methods and lesser use of maladaptive coping methods. METHODS: This study
utilized a cross-sectional design to examine the relationship between gratitude,
coping, and drug use among a sample of drug misusers (N = 105) at a drug
rehabilitation center. Participants completed the gratitude questionnaire (GQ-6),
the joy subscale of the Dispositional Positive Emotion Scale (DPES), the Brief
COPE, and a questionnaire on their drug use. Data were collected in 2015.
RESULTS: Mediation analysis supported the hypothesis and found that adaptive
coping mediated the relationship between gratitude and drug use. However,
mediation was not found for maladaptive coping. Additional analysis found that
adaptive coping as a mediator was not found for joy. CONCLUSION: Results
suggested that gratitude has utility in reducing drug use through the use of more
adaptive coping strategies and this relationship was not simply due to positive
affect. Interventions targeting drug use behavior could consider introducing
gratitude to increase adaptive coping abilities to reduce drug use.
PMID- 28704119
TI - Can "Legal Highs" Trigger Myocardial Infarction? Patients' Characteristics Based
on Published Cases.
PMID- 28704120
TI - Association of Physical Activity with Alcohol Abuse and Dependence in a
Nationally-Representative U.S. Sample.
AB - BACKGROUND: Alcohol use is a pervasive and costly public health problem in the
United States. Relapse rates from alcohol use disorders are high. Although
exercise has been proposed as a strategy to prevent relapse, lifestyle
modification is the least studied aspect of relapse prevention programs,
especially among racial/ethnic minority populations. OBJECTIVE: The current study
assessed whether being physically active was associated with remission from
alcohol abuse or dependence among Black (African American and Afro Caribbean)
adults in the U.S. METHOD: We utilized data on Black adult participants (n =
4,828) from the nationally representative National Survey of American Life (NSAL)
conducted in 2001-2003. Logistic regression models were estimated to assess the
odds of being in 12-month remission or currently meeting DSM-IV criteria for
alcohol abuse or dependence based on level of physical activity, adjusting for
socio-demographic and neighborhood characteristics. RESULTS: People who endorsed
being physically active had higher odds of being in 12-month remission from
alcohol use problems (OR: 1.67, 95% CI: 1.28, 2.17) than people who were
physically inactive, adjusting for individual- and neighborhood-level
characteristics. People who were physically active did not differ significantly
from those who were inactive with respect to odds of currently meeting DSM-IV
criteria for alcohol abuse or dependence. Conclusions/Importance: Physical
activity was positively associated with being in 12-month remission from alcohol
use problems. Longitudinal studies are needed to establish temporal ordering and
to explore exercise as a potential relapse prevention strategy for alcohol use
problems.
PMID- 28704121
TI - Evaluation of In Vitro Antiamoebic Activity of Antimicrobial Agents Against
Clinical Acanthamoeba Isolates.
AB - PURPOSE: The aim of this study was to elucidate in vitro antiamoebic activity of
antimicrobial agents at short exposure times similar to those used for actual
treatment against Acanthamoeba strains isolated from patients with keratitis.
METHODS: The 5 clinical Acanthamoeba isolated in Japan were used in this study.
Identification of genotypes for the Acanthamoeba isolates was performed using
partial 18S ribosomal DNA (rDNA), including the ASA.S1 region sequences.
Fluconazole, miconazole, itraconazole, voriconazole, amphotericin B, natamycin
(pimaricin), and micafungin (antifungal agents), and chlorhexidine (a biguanide
disinfectant), and sulfamethoxazole and paromomycin (antibacterial agents) were
used to determine the antiamoebic activity against Acanthamoeba, which were
determined by 50% and 90% growth inhibitory concentrations (IC50 and IC90)
following exposing to each drug at 25 degrees C for 7 days and 12 h. RESULTS:
Among the tested antimicrobial agents, natamycin strongly inhibited the growth of
all Acanthamoeba isolates at low concentration in both the 7-day (IC90 = 4.1
MUg/mL) and 12-h (IC90 = 11.6 MUg/mL) assays. Additionally, sulfamethoxazole
exhibited strong antiamoebic activity (IC90 = 9.8 MUg/mL) at low concentration in
the 7-day assay. CONCLUSIONS: Our findings showed that natamycin ophthalmic
solution might be an effective agent against Acanthamoeba keratitis.
Additionally, frequent administration of sulfamethoxazole ophthalmic solution or
systemic sulfamethoxazole-trimethoprim is also considered as an effective
treatment for Acanthamoeba keratitis.
PMID- 28704122
TI - Using a Patient and Family Advisory Council as a Mechanism to Hear the Patient's
Voice.
PMID- 28704123
TI - Redelivering Information to Young Adults and Adolescents Treated for Cancer
During Childhood.
PMID- 28704124
TI - beta cell function and insulin resistance in lean cases with polycystic ovary
syndrome.
AB - Obesity is a major factor in development of insulin resistance (IR) and metabolic
features in polycystic ovary syndrome (PCOS) patients. Nearly two-thirds patients
with PCOS (30 of 37 confirmed cases of PCOS) in our previous community based
study were lean, in contrast to Caucasians. Metabolic parameters including IR and
beta cell function have not been characterized well in this group of lean PCOS.
To study the metabolic features including IR and beta cell function in lean PCOS
patients, 53 patients with BMI, <23 kg/m2 were compared with 71 obese PCOS and 45
age and body mass index matched controls. Lean patients had similar beta cell
function and IR as compared to controls and obese patients, though the latter
group had more metabolic abnormality. Fasting c-peptide and its ratio to glucose
were significantly higher in lean patients compared to controls. In subset of
subjects with five point OGTT, disposition index and Matsuda index (MI) showed
significant negative correlation with BMI and blood pressure. MI also negatively
correlated with waist, WHR, and HOMAB. High fasting C-peptide is probably a class
effect as is seen in both lean and obese PCOS.
PMID- 28704125
TI - Effect of Feeding High Gamma-Aminobutyric Acid-Containing Giant Embryo Black
Sticky Rice (Oryza sativa L.) on Anxiety-Related Behavior of C57BL/6 Mice.
AB - The aim of this study was to determine the effect of feeding high gamma
aminobutyric acid (GABA)-containing black sticky rice giant embryo (BSRGE, Oryza
sativa L.) on anxiety-related behavior of C57BL/6 mice. Experimental feedstuff
(BSRGE with high GABA+AIN-76A) and control (AIN-76A) were provided to C57BL/6
mouse for 10 days. Antianxiety effects of BSRGE with high GABA were measured
using an elevated plus maze. On day 8, the number of open arm entries by GABA and
control groups were 1.10 +/- 1.60 (mean +/- SD) and 0.00 +/- 0.00 (P = .030). On
day 10, the number of open arm entries by the GABA group was 2.00 +/- 1.89, which
was significantly (P = .025) higher than that in the control group (0.40 +/-
0.84). On day 8, the time the mice spent in open arm in the GABA group and
control group was 3.60 +/- 7.06 and 0.00 +/- 0.00 sec (P = .068), respectively.
On day 10, the time the mice in the GABA and control groups spent in open arm was
6.20 +/- 5.35 sec and 1.80 +/- 3.82 sec (P = .042), respectively. In repeated
analysis of variance for the number of entries into open arm and time spent in
open arm, significant differences were found between the two groups. Therefore,
BSRGE with high GABA content might have an antianxiety effect. This study can
serve as a preliminary study so that further antianxiety effects of BSRGE can be
determined in more extended animal or clinical research studies in the future.
PMID- 28704126
TI - Economic impact of adalimumab treatment in Japanese patients with rheumatoid
arthritis from the adalimumab non-interventional trial for up-verified effects
and utility (ANOUVEAU) study.
AB - OBJECTIVES: The objective of this study is to evaluate the economic impact of
adalimumab (ADA) on Japanese rheumatoid arthritis (RA) patients. METHODS:
ANOUVEAU was a 48-week multicenter, prospective, observational, single-cohort
study. Work-related outcomes including absenteeism, presenteeism, overall work
impairment (OWI), and activity impairment (AI) were evaluated using the RA
related work productivity and activity impairment (WPAI/RA). The amount of
productivity loss was estimated via multiplication of absenteeism, presenteeism
and OWI by the national average occupational wage for paid worker (PW) and part
time worker (PTW), and via multiplication of AI by the estimated wage for
domestic work for home maker (HM). RESULTS: In this analysis, 1196 patients were
included. At week 48, measures of productivity loss due to absenteeism,
presenteeism, OWI, and AI were significantly improved by administrating ADA to RA
patients in all employment types (PW, PTW, and HM), compared to baseline (p <
.01). Productivity loss of Japanese society by RA disease was estimated to be
$9.80 billion. The annual decrease in productivity loss through ADA
administration to Japanese RA patients was estimated to be $3.76 billion.
CONCLUSIONS: The socioeconomic burden of RA is high, but ADA treatment may reduce
productivity loss related to RA.
PMID- 28704127
TI - Retinal miRNAs variations in a large cohort of inherited retinal disease.
AB - BACKGROUND: Although great efforts have been paid on identification of genetic
predisposition in the inherited retinal disease (IRD), genetic causes of a large
proportion of patients remain a mystery. This dilemma makes us attempt to
speculate that genetic components other than coding genes might be an additional
pool predisposing IRD. In this study, we aim to perform a mutational screening in
a large cohort of IRD patients with a particular focus on retina-specific or
abundant microRNAs (miRs). MATERIAL AND METHODS: A total of 324 unrelated
patients with IRD were recruited. Targeted next-generation sequencing (tNGS) was
performed to survey genetic mutations in 32 known miRs highly expressed in the
retina, followed by validation with Sanger sequencing, co-segregation analysis in
each family, and computational assessments. RESULTS: Novel genotype-phenotype
associations have been uncovered. In total, six different variants in the miRs
were identified, including four rare ones, miR-216a (n.56C>A), miR-216b
(n.43_44insG), miR-7-2 (n.107C>T), and miR-7-3 (n.95G>A). The other two variants,
miR-182 (n.106G>A) and miR-216a (n.105T>A), were considered as polymorphic.
CONCLUSIONS: We for the first time screened candidate retinal miRs in patients
with IRD. Although there is no convincing evidence that these variants are
responsible for the IRD, the results enhance the current knowledge of the
associations between IRD and miRNAs variants.
PMID- 28704128
TI - Commune Health Workers' Methadone Maintenance Treatment (MMT) Knowledge and
Perceived Difficulties Providing Decentralized MMT Services in Vietnam.
AB - BACKGROUND: With the initial establishment of countrywide methadone maintenance
therapy (MMT) system, Vietnam is in the process of expanding and decentralizing
the MMT program to community-based healthcare settings. OBJECTIVE: The study
aimed to measure the MMT-related knowledge and perceived difficulties in treating
patient who use drugs (PWUD) among community-based healthcare providers, e.g.,
commune health workers (CHW), and examine its correlated factors. METHODS: A
total of 300 CHW from 60 communes in two provinces of Vietnam completed a survey
using Audio Computer-Assisted Self-Interview (ACASI) method. Twelve true-or-false
questions were used to assess the CHW's MMT-related knowledge. The CHW's
background characteristics and perceived difficulties treating PWUD were
recorded. RESULTS: The mean MMT knowledge score was 8.2 (SD = 1.2; range: 5-11).
Misconceptions toward the benefits, procedure, and side effects of MMT were
prevalent. The participants perceived varying degrees of difficulties in
recruiting, engaging, and communicating with PWUD. With all covariates holding
constant, younger age (standardized ? = -0.166; p = 0.0078) was associated with
less MMT-related knowledge. Number of PWUD seen in a month and MMT-related
knowledge was associated with less perceived difficulties treating PWUD.
Conclusions/importance: The finding shed lights on the CHW's knowledge gap, which
need to be addressed to facilitate the decentralization of MMT services in
Vietnam. In preparation for a decentralized MMT service delivery model, specially
designed training is warranted to equip CHW with knowledge and confidence to
provide MMT-related services to PWUD.
PMID- 28704129
TI - Electromagnetic information transfer through aqueous system.
AB - Several beneficial effects of the electromagnetic information transfer through
aqueous system (EMITTAS) procedure have previously been reported in vitro. The
clinical potential of this procedure has also started to be evaluated.
Information flow in biological systems can be investigated through chemical and
molecular approaches or by a biophysical approach focused on endogenous
electrodynamic activities. Electromagnetic signals are endogenously generated at
different levels of the biological organization and, likely, play an active role
in synchronizing internal cell function or local/systemic adaptive response.
Consequently, each adaptive response can be described by its specific
electromagnetic pattern and, therefore, correlates with a unique and specific
electromagnetic signature. A biophysical procedure synchronously integrating the
EMITTAS procedure has already been applied for the treatment of articular pain,
low-back pain, neck pain and mobility, fluctuating asymmetry, early-stage chronic
kidney disease, refractory gynecological infections, minor anxiety and depression
disorders. This clinical strategy involves a single treatment, since the EMITTAS
procedure allows the patient to continue his/her own personal treatment at home
by means of self-administration of the recorded aqueous system. A significant and
long-lasting improvement has been reported, showing a potential beneficial use of
this biophysical procedure in the management of common illnesses in an efficient,
effective and personalized way. Data from recent studies suggest that aqueous
systems may play a key role in providing the basis for recording, storing,
transferring and retrieving clinically effective quanta of biological
information. These features likely enable to trigger local and systemic self
regulation and self-regeneration potential of the organism.
PMID- 28704130
TI - Scleral Thinning Documented by Ultrasound Biomicroscopy after Plaque Therapy for
Anterior Ciliary Melanoma.
AB - PURPOSE: To evaluate, by ultrasound biomicroscopy (UBM), changes in scleral
thickness after ruthenium-106 CCB and CCC plaque (Eckert & Ziegler BE-BIG GmbH,
Berlin, Germany) therapy for anterior ciliary melanoma. METHODS: Eleven patients
with anterior ciliary melanoma underwent ruthenium-106 CCB and CCC plaque
radiation with a radiation dose at the tumor apex of 80-100 Gy. UBM measurements
performed prior to and after treatment were as follows: the largest prominence of
the tumor perpendicular to the sclera and scleral thickness at scleral spur, 1.0
mm, and 2.0 mm posteriorly. RESULTS: The article presents one year follow-up
results for each of the 11 patients. The mean regression of the tumor of 24.3+/
9.31% was observed. The thinning of the sclera was statistically significant at
the scleral spur (t=1.80, p <= 0.05) and at maximal tumor thickness (t=1.35,
P=0.05). CONCLUSION: UBM documented significant thinning of the sclera at the
scleral spur and overlying the maximal tumor thickness after Ru-106 CCB and CCC
plaque radiation. Taking into consideration the shortcomings of the study-small
sample size, insufficient probe resolution, and subjectively determined anatomic
landmarks-observed minimal thickness change of the sclera does not necessarily
mean its necrosis. However, thinning of the sclera documented at one year follow
up associated with very slow regression of the tumor indicates the need for the
introduction of the CIA plaque treatment in our patients with anterior ciliary
melanoma.
PMID- 28704131
TI - Portopulmonary hypertension in children: a rare but potentially lethal and under
recognized disease.
AB - Portopulmonary hypertension (PoPH) is defined by the combination of portal
hypertension and precapillary pulmonary arterial hypertension (PAH). Very little
is known about this process in pediatric patients but prognosis is generally
poor. We review our institutional experience and report on five patients with
pediatric PoPH. The median age of PoPH diagnosis was six years and PAH was 14
years. PAH diagnosis was made by echocardiogram in all patients, four of whom
also had cardiac catheterization. The median mean pulmonary artery pressure
(mPAP) was 48.5 mmHg (interquartile range [IQR] = 46-60) with a median pulmonary
vascular resistance index (PVRi) of 9 WU*M2 (IQR = 8-22). All were acute
pulmonary vasodilator testing non-responsive. All patients received targeted
therapies. Three of five patients (60%) died despite an evidence-based approach
to care. Of those who died, timing from the PoPH diagnosis to death ranged from
three days to three years. Based upon our limited experience, PoPH is a disorder
with significant mortality in childhood and challenges in treatment. Future
research, focused on screening and early targeted treatment strategies, may alter
the current dismal prognosis for these children.
PMID- 28704132
TI - Health Insurance Literacy as a Determinant of Population Health.
PMID- 28704133
TI - Understanding Enhanced Recovery After Surgery Guidelines: An Introductory
Approach.
AB - Enhanced Recovery After Surgery (ERAS(r)) is a multimodal, multidisciplinary
approach to surgical care. The ERAS Society has issued recommendations for many
surgical procedures that address best practices in preoperative, intraoperative,
and postoperative management. When implementing a new ERAS protocol, the length
and detail of the recommendations can be overwhelming. In this study, the general
principles of the ERAS guidelines are summarized and workload is distributed
among the different members of the care team. This compartmentalized approach
provides an easier way to involve key personnel in the ERAS process and assigns a
role for everyone in making ERAS a success.
PMID- 28704134
TI - Pulmonary vascular effect of insulin in a rodent model of pulmonary arterial
hypertension.
AB - Pulmonary arterial hypertension (PAH) is associated with metabolic derangements
including insulin resistance, although their effects on the cardiopulmonary
disease are unclear. We hypothesized that insulin resistance promotes pulmonary
hypertension (PH) development and mutations in type 2 bone morphogenetic protein
receptor (BMPR2) cause cellular insulin resistance. Using a BMPR2 transgenic
murine model of PAH and two models of inducible diabetes mellitus, we explored
the impact of hyperglycemia and/or hyperinsulinemia on development and severity
of PH. We assessed insulin signaling and insulin-mediated glucose uptake in human
endothelial cells with and without mutations in BMPR2. PH developed in control
mice fed a Western diet and PH in BMPR2 mutant mice was increased by Western
diet. Pulmonary artery pressure correlated strongly with fasting plasma insulin
but not glucose. Reactive oxygen species were increased in lungs of insulin
resistant animals. BMPR2 mutation impaired insulin-mediated endothelial glucose
uptake via reduced glucose transporter translocation despite intact insulin
signaling. Experimental hyperinsulinemia is strongly associated with PH in both
control and BMPR2-mutant mice, though to a greater degree in those with BMPR2
mutation. Human pulmonary endothelial cells with BMPR2 mutation have evidence of
reduced glucose uptake due to impaired glucose transporter translocation. These
experiments support a role for hyperinsulinemia in pulmonary vascular disease.
PMID- 28704135
TI - 'Top, bottom, versatile': narratives of sexual practices in gay relationships in
the Cape Metropole, South Africa.
AB - Sexual practices among gay and other men who have sex with men are evolving in
South Africa and heteronormative stereotypes are being contested. This paper
draws from a larger qualitative study on how men construct a gay identity and
negotiate their relationships within contemporary South African contexts,
following constitutional and legal changes, in this respect. A feminist, social
constructionist approach was used to collect and analyse data from in-depth
interviews with 15 self-identified gay men, aged 20 to 46 years, drawn from a
university in the larger Cape Metropole, South Africa. Interviews were audio
recorded, transcribed verbatim and analysed using thematic and narrative
analysis. 'Bottoms' revealed being powerful in receptive sex. Other men
deconstructed the binaries of masculine/feminine and resisted heteronormativity
by engaging in fluid constructions in their relationships, whereby participants
'switched' or 'flipped' or did not recognise stereotypical roles when practising
sex. There may be value in making these flexible and reciprocal sexual practices
better known about and promoted as non-normative African models of sexual
practice.
PMID- 28704136
TI - Factors influencing outcomes in patients with Eisenmenger syndrome: a nine-year
follow-up study.
AB - In patients with Eisenmenger syndrome, life expectancy is usually longer than in
patients with other forms of pulmonary arterial hypertension (PAH). We conducted
a cohort study in which patients were followed over a long period of time in an
attempt to identify potential predictors of clinical outcomes. Sixty-seven
treatment-naive patients were enrolled (age range = 12-60 years; median age = 33
years). Baseline demographic, diagnostic, and functional parameters, plasma
levels of endothelial dysfunction markers, and treatment-related data were tested
for possible correlations with event-free survival. Patients were started on oral
PAH drugs at the beginning of follow-up (n = 23), during follow-up (n = 33), or
remained untreated (n = 11). The duration of follow-up was 0.54-9.89 years
(median = 7.13 years), with an overall survival rate of 82% and an event-free
survival rate of 70%. The estimated mean for event-free survival time was 7.71
years (95% confidence interval [CI] = 6.86-8.55 years). Of the 16 variables that
were analyzed, the duration of exposure to PAH drugs was identified as an
independent protective factor (hazard ratio [HR] = 0.25 for quartiles, 95% CI =
0.14-0.47, P < 0.001). The initial functional class (HR = 3.07; 95% CI = 1.01
9.34; P = 0.048), the severity of right ventricular dysfunction (HR = 2.51 [mild,
moderate or severe dysfunction]; 95% CI = 1.22-5.19; P = 0.013) and plasma von
Willebrand factor concentration (HR = 1.74 for quartiles; 95% CI = 1.07-2.83; P =
0.026) were identified as risk factors. The length of exposure to oral PAH
therapies influences survival favorably in Eisenmenger patients. This may be of
interest for communities where access to medications is restricted.
PMID- 28704137
TI - Uruguayan secondary school students speak up about tobacco: results from focus
group discussions in and around Montevideo.
AB - This qualitative research study investigated intrapersonal, interpersonal, and
environmental factors that shape young adolescent tobacco use behaviors in
Uruguay. Focus groups were conducted in the summer of 2012 and fall of 2013 in
four secondary schools in Montevideo, Uruguay, including two private schools and
two public schools. A total of four focus groups were led in each school,
composed of 4-6 students each, 16 focus groups in total. Data analysis utilized
NVivo software and included deductive and inductive content analysis.
Overwhelmingly, students reported that the onset of smoking occurred in the
second year of secondary school. The primary intrapersonal factors that were
found to be universal among respondents identified that smoking was a performance
in groups, to garner attention from their peers. Students interviewed most often
stated that the greatest interpersonal factors for smoking were to look older, as
a rite of passage, and for group membership. Environmental factors cited most
often indicate that they smoked during unsupervised time, either at night or
around the short Uruguayan school day. Focus group interviews revealed that
adolescents had easy access to cigarettes for purchase through small family owned
grocery stores, even though laws exist preventing the sale of cigarettes to
minors. Few differences were cited between strata related to cigarette use in
adolescents. The differences that do exist are most apparent across gender,
though there were a few observed differences when stratified by public and
private school. Findings from this study indicate that key factors across
ecological levels (intrapersonal, interpersonal, and environmental) should be
taken into consideration when designing tobacco prevention programs for youth in
Uruguay. A multiple-component approach which addresses risk factors at all of
these levels, implemented in schools, may be particularly well-suited to this
setting.
PMID- 28704138
TI - Evaluation of a successful aging promotion intervention program for middle-aged
adults in Taiwan.
AB - PURPOSE: This study was to implement and evaluate a successful aging intervention
program for middle-aged private insurance beneficiaries. METHODS: The
participants were recruited from the staff and middle-aged clients for the
experimental and control groups of a private insurance company. The two client
(experimental and control) groups were matched by comparable age groups, gender,
education, and purchased insurance types. The intervention program provided for
the staff and the experimental group consisted of a series of educational courses
on the topics about successful aging and preparation for 4 months. In total,
there were 40 staff members, in addition to the 74 members of the experimental
group and 60 members of the control group participating in the study. RESULTS:
After the intervention, the rate of physical activity and exercise significantly
improved for the staff and for the intervention group. There were significant
improvements in behaviors associated with doing exercise and living a less
sedentary lifestyle and in the utilization of health examinations, and
improvements in fitness and blood pressure. CONCLUSION: The successful aging
intervention program significantly improved awareness of successful aging,
exercise behavior and fitness.
PMID- 28704139
TI - Influencing Safety in Australian Agriculture and Fisheries.
AB - BACKGROUND: Improving the health and safety of those working in Australian
agriculture and fishery industries is a recognized priority area for preventative
activities. With Australian agricultural industries being among the nation's most
dangerous workplaces, there is a need for action. While there are currently known
solutions, their implementation is limited. Influential agents, i.e., people who
can influence others, are important for helping engender action to enact
solutions into practice. OBJECTIVE: This study examines agents that influence
safety behavior either negatively (barriers) or positively (facilitators), in the
Australian agriculture and fishery industries. METHODS: Focus groups were
conducted with producers and industry representatives. Thematic analysis
identified barriers and facilitators to improve health and safety. These were
assessed against the Socioecological Model, which considers the various, and
often intersecting, human (intrapersonal, i.e. values and attitudes, peers,
familial, and cultural) factors influencing safety behavior. RESULTS: Seven
categories of human influences were identified: self, peers, family,
intergenerational change, industry agents, government agents, and other. Peers
(including direct managers) and family were seen to be direct influencers.
Individuals signal to others that safety is valued and important. This is
reinforced by experience, skill, attitudes, and behavior. Safety practice
knowledge acquisition occurred via the family unit, specific training, industry,
or knowledge transfer between industries. Government influence predominately
focused on legislation and while the source of this influence is distant, it does
influence behavior. CONCLUSIONS/RECOMMENDATIONS: There is a need to support
comprehensive programs. These should include strengthening relationships via peer
to-peer networking, sharing information about safety initiatives, appropriate
legislation, and enhancing leadership of all influencers with regard to safety.
PMID- 28704140
TI - Capitalizing on Federal Agencies' Intentions To Protect Youth Working in
Agriculture.
AB - Nearly 750,000 youth work on farms across the United States. The U.S. Department
of Labor's (U.S. DOL) Fair Labor Standards Act (FLSA) Hazardous Occupations
Orders for Agriculture (HOOA) applies to approximately 37% of these youth. The
HOOA regulations had not been updated since their inception in the late 1960s and
the early 1970s. An attempt by U.S. DOL to update the regulations in 2011 was met
with fierce opposition by the agricultural community, and the proposed updated
regulations were withdrawn. One impactful outcome of these two events was a
rededication by USDA and the farm community to address agricultural youth farm
safety through education rather than through regulation. An agriculturally based
National Steering Committee has developed consensus Belief Statements and Guiding
Principles to proactively influence agricultural youth safety. In this case, USDA
was clearly a 'sphere of influence' for youth agricultural safety.
PMID- 28704141
TI - It's no laughing matter: An exploratory study of the use of ironic versus
sarcastic humor in health-related advertising messages.
AB - We examined the persuasive effects of ironic and sarcastic versus no humor
appeals in health messages and the potential differential effects of ironic
versus sarcastic humor. Findings of a controlled experiment (N = 303) suggested
that sarcastic messages, as compared to no humor messages, resulted in less
negative affect, more counterarguing, and decreased perceived argument strength.
Ironic messages led to more counterarguing than no humor messages. Significant
differences in counterarguing, perceived argument strength, and attitudes toward
the risky behavior were detected between the two humor types. Counterarguing
mediated the indirect effect of message type on attitudes toward the risky
behavior.
PMID- 28704142
TI - Motivations behind donations for health-related organizations: Threat appraisal
and coping appraisal-the case of the ALS Ice Bucket Challenge.
AB - This study explores the influence of social media involvement and other factors
on individuals' donation intentions in the context of the ALS Ice Bucket
Challenge. An online survey with 306 participants revealed that social media
involvement had a direct effect on intentions to contribute donations and had an
indirect effect that was mediated by the response efficacy on intentions after
controlling for individuals' issue involvement with the disease.
PMID- 28704143
TI - North Carolina State Agencies Working to Prevent Agricultural Injuries and
Illnesses.
AB - Over the past 25 years, the North Carolina Departments of Labor, Agriculture and
Consumer Services, and Health and Human Services have worked with farmers,
farmworkers, commodity and trade associations, universities, and cooperative
extension agents to develop programs to decrease the occurrence of injuries and
illnesses among agricultural workers and their families. The Bureau of
Agricultural Safety and Health in the North Carolina Department of Labor helped
craft the Migrant Housing Act, created the Gold Star program, and developed
numerous projects promoting rural highway safety and farm safety. The Structural
Pest Control & Pesticides Division in the North Carolina Department of
Agriculture & Consumer Services administers programs funded by the Pesticide
Environmental Trust Fund (PETF), including the Pesticide Container Recycling
Program, Pesticide Disposal Assistance Program (PDAP), and Soil Fumigation
Training. The Occupational and Environmental Epidemiology Branch (OEEB) in the
North Carolina Department of Health and Human Services developed public health
surveillance programs for pesticide incidents and carbon monoxide poisoning.
These projects, programs, and policies demonstrate the work that North Carolina
state agencies are doing to improve the health of agricultural workers and their
families.
PMID- 28704144
TI - Orbital ultrasonography in the diagnosis of neoplastic extraocular muscle
enlargement.
AB - Neoplastic infiltration of the extraocular muscle (EOM) is a rare condition which
can pose a diagnostic dilemma due to its rarity and overlapping ultrasonographic
features with orbital myositis. The ultrasonographic features of neoplastic
enlargement of EOM have not been systematically studied and previously have been
described in only a few case reports. Orbital ultrasonography, in conjunction
with the pattern of ocular misalignment, was assessed for its potential role in
identifying patients with neoplastic EOM enlargement. Retrospective chart review
of patients with neoplasm and myositis. The clinical features of 8 patients with
neoplastic infiltration of the EOM were compared to 15 patients with myositis. In
the neoplastic group the width of the EOM was (10.5 mm) almost twice the normal
width of the muscle with myositis (p < 0.001). All the muscles in the neoplastic
category were low to medium reflective. Paretic deviation was seen in 4/8(50%),
purely restrictive in 2/8 (25%) and combined pattern in 2/8 (25%) were noted. In
the myositis group the average EOM enlargement was 5.8 mm and all muscles showed
low reflectivity. Although ultrasonographic features overlapped between the 2
groups paretic deviations were more common in the neoplastic group versus the
myositis group (50% versus 7%). Neoplastic muscle enlargement tends to be larger
with paretic deviations of ocular motility seen clinically. These findings in a
patient with EOM enlargement should raise the suspicion of neoplasm as the
etiology and further work up should be considered.
PMID- 28704145
TI - Adult Zebrafish (Danio rerio): An Alternative Behavioral Model of Formalin
Induced Nociception.
AB - The zebrafish (Danio rerio) has been proposed as a low-cost and simple
alternative to the use of higher vertebrates in laboratory research on novel
compounds with antinociceptive potential. In this study, we tested adult
zebrafish (Danio rerio) as an alternative behavioral model of formalin-induced
nociception. We evaluated the nociceptive effect of 0.1% formalin (3 or 5 MUL;
intramuscularly [i.m.]), applied into the tail or lips, on locomotor activity,
using as parameter the number of times the fish crossed the lines between the
quadrants of a glass Petri dish during the neurogenic stage (0-5 min) and the
inflammatory stage (15-30 min). The behavioral model was validated by testing the
antinociceptive effect of morphine and indomethacin (standard analgesic drugs
used in the formalin test of rodents). We also tested whether the effect of
morphine could be modulated by naloxone, an opioid antagonist. The effect of
morphine and indomethacin on zebrafish locomotor behavior was evaluated with the
open field test. The white/black test was used to rule out the anxiolytic effect
of 0.1% formalin injected into the tail on adult zebrafish. Formalin (0.1%; 3 and
5 MUL injected into the tail) increased significantly the nociceptive behavior of
the adult zebrafish in both stages (p < 0.001 vs. control). Morphine and
indomethacin (both 0.2 mg/mL; 20 MUL; intraperitoneally [i.p.]) significantly
inhibited nociception induced with formalin (5 MUL injected i.m. into the tail)
in both stages (p < 0.001). Naloxone blocked the antinociceptive effect of
morphine. No influence on locomotion was observed. Locally administered formalin
(injected into the tail) induced nociception, but not anxiety. The results
suggest that the adult zebrafish behavioral model is a feasible alternative to
more conventional laboratory models used in research on novel compounds with
antinociceptive potential.
PMID- 28704146
TI - Legacy Interventions With Patients with Co-Occurring Disorders: Legacy
Definitions, Life Satisfaction, and Self-Efficacy.
AB - BACKGROUND: Individuals with co-occurring disorders tend to avoid interaction
with others. To instill hope, legacy intervention aims to highlight past
experiences while managing life stressors for a positive outlook. Participants
take part in legacy activities-crafting tangible projects and recording one's
life events-in order to actualize a personal sense of legacy. OBJECTIVES: This
pre-posttest research tested whether legacy intervention in a partial hospital
program (PHP) on reframing past experiences through creative activities could
increase life satisfaction and self-efficacy among adults with co-occurring
substance misuse and mental health symptoms. METHOD: Eighty consented patients
with co-occurring disorders were randomly assigned to two groups with 62
participants continuing: 37 in legacy intervention (LI) and 25 in partial
hospital program only (PHP-only). LI participants were engaged in both PHP and
legacy activities. Ten group sessions were held over the course of five weeks for
cohorts of 10-15 adult patients in each intervention. Sense of legacy was
measured to ensure that LI patients received the appropriate legacy dosage.
RESULTS: With RANOVA analyses between and among three time points, life
satisfaction was significantly higher in the LI group with group interaction
effect over time. In terms of self-efficacy, both groups showed positive changes
but no significant difference could be found between the two groups over time and
the interaction (time X group) effect was not significant. IMPORTANCE: The legacy
definitions gathered from the LI group were consistent with existing literature
and showed three additional themes: children's involvement, concreteness, and
life continuation after death.
PMID- 28704147
TI - Customers' Precedence for Service Quality Dimensions in Indian Private Healthcare
Setting: A Ridit Approach.
AB - Changes in demographic and sociocultural environment, improved health awareness,
and information technology have considerably changed the outlook of healthcare
sector in India. While both the public and the private healthcare sectors have
priority of increasing access while minimizing costs, they try hard to achieve
goals without letting the quality suffer. Customers with rising disposable income
no longer have faith in the public healthcare system and are willing to migrate
to the private healthcare sector, which is more professional, technology savvy,
and trustworthy. However, there are enough loopholes in the private healthcare
sector that are yet to be plugged. The purpose of this research study was to
identify and assess the relative importance of the diverse service quality
dimensions and prioritize them to draw meaningful conclusions. Survey responses
from 370 customers were analyzed using factor analysis to find underlying
relationships between the survey items. This allowed the individual items to be
placed into related groups. Independently, a ridit analysis was conducted to
determine the relative importance of each item to the survey respondents. Based
on the ridit analysis a priority ranking was assigned to each item. An analysis
was then undertaken of the degree to which the items grouped into each particular
factor tended to have high or low priority rankings. The results of the study may
be helpful to the managers of the private healthcare sector to focus their
strategies and plan their efforts in line with the findings to gain superior
customer satisfaction and retention.
PMID- 28704148
TI - "I Was Not Sick and I Didn't Need to Recover": Methadone Maintenance Treatment
(MMT) as a Refuge from Criminalization.
AB - BACKGROUND: Methadone Maintenance Treatment (MMT) in the United States (U.S.) has
been undergoing a shift towards conceptualizing the program as recovery-based
treatment. Although recovery is seen by some as a means to restore MMT to its
rightful position as a medically-based treatment for addiction, it may not
represent the experiences, or meet the needs of people who use drugs (PWUD), many
of whom who use the program as a pragmatic means of reducing harms associated
with criminalization. OBJECTIVES: To examine alternative constructions of MMT in
order to produce a richer, more contextualized picture of the program and the
reasons PWUD employ its services. METHODS: This paper uses semi-structured
interviews with 23 people on MMT (either currently or within the previous two
years). RESULTS: Most participants linked their use of MMT to the structural
legal context of prohibition/criminalization rather than through the narrative of
the recovery model. Responses suggested the recovery model functions in part to
obscure the role of criminalization in the harms PWUD experience in favor of a
model based on individual pathology. Conclusions/Importance: In contrast to the
recovery model, MMT cannot be understood outside of the structural context of
criminalization and the War on Drugs which shape illegal drug use as a difficult
and dangerous activity, and consequently position MMT as a way to moderate or
escape from those harms.
PMID- 28704149
TI - Amputation predictors in diabetic foot ulcers treated with hyperbaric oxygen.
AB - OBJECTIVE: Although hyperbaric oxygen therapy (HBOT) has long been used for
diabetic foot ulcers (DFUs), its effectiveness is still controversial. The aim of
this study was to investigate the efficacy of HBOT in the management of DFUs and
identify amputation predictors. METHOD: Patients with chronic DFUs (Wanger grade
2-5) were included in the study, which took place between January 2010 and
December 2012. HBOT, 100% oxygen, 2.4 atmosphere absolute (ATA) for 120 minutes,
was administered to all patients in addition to standard treatment. DFUs were
monitored for at least 3 years, or until healing or amputation occurred. RESULTS:
Patients with a total of 146 chronic DFUswere recruited. Complete healing (69.6%)
and significant improvement (17.9%) was observed in 87.5% of the patients. The
cases with no improvement resulted in amputation (minor amputation: 15.0%; major
amputation: 8.2%). The duration of diabetes (p=0.037), new wound formation
(p=0.045), C-reactive protein (p=0.001) and Wagner grade (p=0.0001) were
correlated with amputation in multiple regression analysis. Mortality was higher
in the amputation group than in the non-amputation group (47.1 % versus 21.4 %,
p=0.007). CONCLUSION: The inclusion of HBOT with standard treatment and a
multidisciplinary approach may be useful in the treatment of DFUs. We found the
most important predictors of amputation to be Wagner grade and wound infection.
Multicentre, prospective, randomised studies are needed to provide more evidence.
PMID- 28704150
TI - Measurement of pH, exudate composition and temperature in wound healing: a
systematic review.
AB - OBJECTIVE: To assess the potential of measurements of pH, exudate composition and
temperature in wounds to predict healing outcomes and to identify the methods
that are employed to measure them. METHOD: A systematic review based on the
outcomes of a search strategy of quantitative primary research published in the
English language was conducted. Inclusion criteria limited studies to those
involving in vivo and human participants with an existing or intentionally
provoked wound, defined as 'a break in the epithelial integrity of the skin', and
excluded in vitro and animal studies. Data synthesis and analysis was performed
using structured narrative summaries of each included study arranged by concept,
pH, exudate composition and temperature. The Evidence Based Literature (EBL)
Critical Appraisal Checklist was implemented to appraise the quality of the
included studies. RESULTS: A total of 23 studies, three for pH (mean quality
score 54.48%), 12 for exudate composition (mean quality score 46.54%) and eight
for temperature (mean quality score 36.66%), were assessed as eligible for
inclusion in this review. Findings suggest that reduced pH levels in wounds, from
alkaline towards acidic, are associated with improvements in wound condition.
Metalloproteinase-9 (MMP-9), matrix metalloproteinase-2 (MMP-2), tissue inhibitor
of metalloproteinase (TIMP), neutrophil elastase (NE) and albumin, in descending
order, were the most frequently measured analytes in wounds. MMP-9 emerged as the
analyte which offers the most potential as a biomarker of wound healing, with
elevated levels observed in acute or non-healing wounds and decreasing levels in
wounds progressing in healing. Combined measures of different exudate components,
such as MMP/TIMP ratios, also appeared to offer substantial potential to indicate
wound healing. Finally, temperature measurements are highest in non-healing,
worsening or acute wounds and decrease as wounds progress towards healing.
Methods used to measure pH, exudate composition and temperature varied greatly
and, despite noting some similarities, the studies often yielded significantly
contrasting results. Furthermore, a limitation to the generalisability of the
findings was the overall quality scores of the research studies, which appeared
suboptimal. CONCLUSION: Despite some promising findings, there was insufficient
evidence to confidently recommend the use of any of these measures as predictors
of wound healing. pH measurement appeared as the most practical method for use in
clinical practice to indicate wound healing outcomes. Further research is
required to increase the strength of evidence and develop a greater understanding
of wound healing dynamics.
PMID- 28704151
TI - Erratum.
PMID- 28704152
TI - Letters.
PMID- 28704153
TI - Introducing the new WUWHS executive and editorial board.
PMID- 28704154
TI - The use of a micropore particle technology in the treatment of acute wounds.
AB - OBJECTIVE: A clinical audit was performed to evaluate whether Acapsil micropore
particle technology (MPPT) powder could improve the management of acute wounds to
heal by secondary intention. METHOD: Wounds, which could be characterised as
sloughy, wet and probably infected, normally managed by debridement followed by
negative pressure wound therapy (NPWT), were included in the evaluation. The MPPT
powder was applied topically to the wound surface either once daily or on
alternate days, with each wound receiving a total of two to five applications.
Most patients had NPWT after the MPPT powder treatment had finished to assist
healing. RESULTS: The study included nine patients with dehisced surgical wounds
and one with a category IV pressure ulcer (PU). The wounds were generally covered
in slough, exudate and showing signs of local infection. The topical MPPT powder
rapidly desloughed the wounds, controlled exudate levels, promoted granulation
and was well tolerated. All wounds proceeded towards closure. CONCLUSION:
Comparison of the present data with MPPT powder to standard treatment suggests
that the speed of healing using MPPT was improved. Further examination is
required to determine if this reduces dressing changes, nursing time, and
financial cost.
PMID- 28704155
TI - Food for thought: innovation and debate.
PMID- 28704156
TI - Quality of life in patients with leg ulcers: results from CHALLENGE, a double
blind randomised controlled trial.
AB - OBJECTIVE: We recently showed the superiority of a matrix metalloproteinase (MMP)
modulating dressing (foam impregnated with NOSF, nano-oligosaccharide factor)
compared with a lipidocolloid matrix (TLC) control dressing in median wound area
reduction (WAR). Here we report the results from the same study assessing the
performance and safety of TLC-NOSF in the local management of venous leg ulcers
(VLUs) or mixed leg ulcers and determining its impact on the patient's health
related quality of life (HRQoL). METHOD: A superiority randomised double-blind
controlled trial was conducted on patients presenting with a non-infected leg
ulcer (VLUs or mixed leg ulcers) of predominantly venous origin (ABPI >0.8), with
a surface area ranging from 5 to 50cm2 and a duration of 6 to 36 months. Patients
were randomly allocated to either the TLC-NOSF matrix foam (UrgoStart) dressing
group or to the neutral TLC foam dressing group (UrgoTul Absorb). All received
appropriate compression therapy and the wounds were assessed blindly (clinical
examination, wound area tracing and photographic record) every 2 weeks for a
period of 8 weeks, or until complete closure. A secondary endpoint, described
here, was the patient's HRQoL, documented by the patient, through the EuroQol 5D
tool (EQ-5D) questionnaire and visual analogue scale (VAS). RESULTS: In total,
187 patients were randomised to either the TLC-NOSF group (n=94) or the control
dressing group (n=93). The two groups were well balanced at baseline with regard
to wound and patient characteristics. In the HRQoL questionnaire (EQ-5D), the
pain/discomfort and anxiety/depression dimensions were significantly improved in
the TLC-NOSF group versus the control one (pain/discomfort: 1.53+/-0.53 versus
1.74+/-0.65; p=0.022, and anxiety/depression: 1.35+/-0.53 versus 1.54+/-0.60,
p=0.037). The VAS score was better in the test group compared with the control
group (72.1+/-17.5 versus 67.3+/-18.7, respectively), without reaching
significance (p=0.072). Acceptability and tolerance of the two products were
similar in both groups. CONCLUSION: The double-blind clinical trial has
demonstrated that the TLC-NOSF matrix dressing promotes faster healing of VLUs
and mixed leg ulcers and significantly reduces the pain/discomfort and
anxiety/depression experienced by the patients. These results suggest that
acceleration of VLU healing could improve the HRQoL of the patients and reduced
the emotional and social burden of these chronic wounds.
PMID- 28704157
TI - Survival rate and pressure ulcer prevalence in patients with and without
dementia: a retrospective study.
AB - OBJECTIVE: This retrospective study aimed to investigate the prevalence of
pressure ulcers (PUs) in older patients with advanced dementia versus older
patients without dementia but with other comorbidities, such as diabetes,
ischaemic heart disease and chronic renal failure. PUs were thought to be more
prevalent and to present a higher risk of mortality in patients with dementia.
METHOD: PUs were assessed on admission using the European Pressure Ulcer Advisory
Panel (EPUAP) staging system. Patients were classified as either with or without
dementia according to Reisberg's functional assessment staging test (FAST). The
prevalence of PUs and the survival rates were analysed and compared in both
groups. The combined effect of PUs and dementia on survival was assessed using
the Cox proportional hazard model. RESULTS: The median survival rate of patients
with PUs and dementia was 63 days, significantly lower than in patients with PUs
without dementia 117 days. Both groups had similar other comorbidities.
CONCLUSION: These findings underscore the requirement for geriatricians and
health professionals to be more vigilant in examining PUs as dementia progresses.
PMID- 28704158
TI - Factors Associated with Occurrence of Radiation-induced Optic Neuropathy at
"Safe" Radiation Dosage.
AB - BACKGROUND: Radiation-induced optic neuropathy (RION) is a rare, and often
visually devastating, complication of radiation therapy (RT) near the anterior
visual pathways. METHODS: A retrospective case series of patients who developed
RION at a tertiary medical center, followed by a case-control study comparing
RION cases with matched controls who received RT. RESULTS: Thirteen patients (18
eyes) with RION were identified. Radiation modalities included external beam
photon radiation, whole brain radiation, stereotactic radiosurgery, proton beam,
and unknown. Most patients received doses below published "safe" thresholds (<55
Gy; <8-10 Gy for stereotactic radiosurgery). There was no statistically
significant difference in prevalence of vasculopathic factors between cases and
controls; on subgroup analysis in three patients who received surprisingly low
radiation doses, smoking (p=0.05) and hypertension (p=0.02) appeared more
prevalent. CONCLUSION: RION can occur at doses below published "safe" thresholds
and with different RT modalities. Smoking and hypertension might be risk factors
for RION.
PMID- 28704159
TI - One does not fit all: Health audience segmentation and prediction of health
behaviors in cancer prevention.
AB - The purpose of this study is to propose a health belief model-based approach to
segmenting health audiences in order to improve targeting of cancer prevention
efforts. This study also examines how the identified health segments differ in
cancer prevention behaviors. Using data from the 2013 Health Information National
Trends Survey, a cluster analysis resulted in three distinct health audience
groups: (a) health aware, (b) health at risk, and (c) health in confidence.
MANOVA tests indicate that these segments differ significantly regarding healthy
diet and exercise. The findings inform cancer prevention campaigns targeting
priority audiences.
PMID- 28704160
TI - Assessment of Tribal Bison Worker Hazards Using Trusted Research Facilitators.
AB - OBJECTIVES: Agriculture is one of the most hazardous industries in the United
States. Within agriculture, livestock handling is particularly dangerous. While
injury and fatality rates for bison handlers have not been reported, workers in
many of the newly established tribal bison herds have limited safety training and
animal handling experience, making this a vulnerable workforce. Veterinarians and
herd managers, working with tribal bison herds, recognized the need for
improvement in the working environment and for worker safety training. In
response, partnerships were established and a pilot project was developed in
order to characterize risks and hazards associated with bison handling under
contemporary reservation field conditions. Individuals and organizations working
as change agents included veterinarians at the University of Nebraska - Lincoln
School of Veterinary Medicine, a tribal advocacy organization, the Intertribal
Buffalo Council and researchers at the Central States Center for Agricultural
Safety and Health at the University of Nebraska Medical Center. METHODS: This is
a mixed-methods study and data were gathered through closed and open-ended
questions pertaining to bison worker safety hazards. A veterinarian gathered data
through observational safety audits at bison herding locations. American Indian
bison herd managers completed surveys using a convenience sampling method.
RESULTS: Findings indicate that the most common worker safety risks are
associated with the use of high-stress handling methods and substandard
facilities and equipment. Adverse environmental conditions also contribute to
worker health risks. Most common causes of injuries included those caused by
equipment and tools, adverse weather, and direct contact with animals.
CONCLUSION: This collaborative research study contributes to a better
understanding of hazards faced by tribal bison workers. Findings from this
research influenced the ITBC in their decision to add worker safety and health
training to the agenda of their yearly conference and promote tailgate trainings
for their workers. UNL veterinarians have taken the lessons learned from this
research and provided safety and health information to mangers of other non
tribal bison herds. This research partnership will continue with a 5-year
research study focusing on best management practices and establishing training to
improve the health and safety bison workers.
PMID- 28704161
TI - Cardiovascular safety of low-dose fenfluramine in Dravet syndrome: a review of
its benefit-risk profile in a new patient population.
AB - OBJECTIVE: Dravet syndrome (DS) is a rare, treatment-resistant epilepsy syndrome
for which current treatment regimens are often ineffective. Fenfluramine is
currently in development for treatment of DS, based on reports in the 1980s and
1990s of its anti-epileptic activity in pediatric patients with intractable
epilepsy. However, fenfluramine was withdrawn from global markets in 1997
following reports of its association with pulmonary hypertension and heart valve
disease in adult patients treated for obesity. This review was conducted to
assess cardiac safety of fenfluramine when used at lower doses for treatment of
DS. METHODS: Pubmed was searched for clinical studies of fenfluramine in obese
adults who reported incidence of heart valve disease. These data were reviewed
against published results from Belgian patients with DS who have been treated
with low-dose fenfluramine for up to 28 years. RESULTS: Nine controlled studies
of fenfluramine and related compounds (dexfenfluramine and/or phentermine) which
assessed incidence and severity of cardiac valve disease in 3,268 treated
patients and 2,017 control subjects have been reported. Mild or greater aortic
valve regurgitation was found in 9.6% of treated patients compared with 3.9% of
control subjects, and moderate or greater mitral valve regurgitation was found in
3.1% of treated patients and 2.5% of control subjects. Nineteen DS patients have
been treated for up to 28 years with 10-20 mg/day fenfluramine, with no clinical
signs or symptoms of cardiac valve disease or pulmonary hypertension. Slight and
clinically unimportant changes in valve structure have been seen on
echocardiography in five patients at some time during the observation period.
CONCLUSIONS: A different benefit-risk relationship appears to be emerging when
fenfluramine is used at low doses for extended periods in young patients with DS.
Continued cardiac assessments during ongoing Phase 3 clinical trials will provide
additional safety information for this potential new and effective treatment.
PMID- 28704162
TI - Thioester-containing proteins: At the crossroads of immune effector mechanisms.
PMID- 28704163
TI - Prevalence of macular abnormalities assessed by optical coherence tomography in
patients with Usher syndrome.
AB - BACKGROUND: To investigate the prevalence of macular abnormalities in patients
affected by Usher syndrome (USH), by comparing the clinical findings between two
types (i.e., USH1 and USH2). MATERIAL AND METHODS: A retrospective study was
performed by reviewing optical coherence tomography (OCT) in 134 USH patients to
determine the presence of macular abnormalities, including cystoid macular edema
(CME), epiretinal membrane (ERM), vitreo-macular traction syndrome (VMT), and
macular hole (MH). RESULTS: Macular abnormalities were observed in 126/268
(47.0%) examined eyes. The most frequent abnormality was ERM observed in 51 eyes
(19%), followed by CME observed in 42 eyes (15.7%). Moreover, CME was
significantly (p < 0.05) associated with younger age (CME: 30.1 +/- 11.1 years;
without CME: 36.9 +/- 14.9 years), whereas VMT and full thickness MH were
associated with older age (p < 0.05). Moreover, a significantly (p < 0.05)
decreased best-corrected visual acuity was associated with MH compared to eyes
without MH. Finally, CME was more frequent in USH1 compared to USH2. CONCLUSION:
Our study, for the first time in the literature, showed the distribution of all
macular abnormalities assessed by SD-OCT in a large USH cohort, comparing USH1
and USH2 patients. We observed that ocular abnormalities are highly prevalent in
USH patients compared to general population, with ERM and CME being the most
common alterations. Based on these findings, OCT screening in USH patients is
recommended for early detection of macular changes and early treatment.
PMID- 28704164
TI - Maternal Problem Drinking and Child Mental Health.
AB - BACKGROUND: Offspring of individuals with alcohol use disorders have been shown
to have elevated risk for mental health problems. OBJECTIVES: To examine the
association between maternal problem drinking and child mental health as assessed
by three informants in three European countries. METHODS: Data were drawn from
the School Child Mental Health in Europe study. Maternal alcohol use was assessed
using the alcohol use disorders identification test. Child mental health was
assessed using the mother and teacher versions of the strengths and difficulties
questionnaire, and the child self-reported Dominic interactive. Analyses were
performed on 2,678 individuals, 6-11 year olds. RESULTS: Adjusting for variables
associated with maternal drinking, among children eight years old or younger,
excessive drinking was not significantly associated with mental health problems,
whether reported by the mother, teacher or by the child. However, among girls
eight years old and above, problem drinking was associated with conduct problems
as reported by the mother (OR = 4.19), teacher reported total difficulties (OR =
4.69), and peer relationship problems (OR = 8.86). It was also associated with
the presence of any child-reported disorder (OR = 3.88), externalizing (OR =
5.55) and internalizing disorders (OR = 4.42). Conclusions/Importance: Adjusting
for sociodemographic variables and for psychological distress, maternal problem
drinking was not significantly associated with child mental health problems in
boys or in girls ages six to eight. The association was only present among girls
ages 8-11. Examining relationships between mothers and their daughters in the
peripubertal period may be a critical window for the development of effective
intervention strategies.
PMID- 28704165
TI - Specific Monoclonal Antibody Against Bcr/Abl Out-of-Frame Alternative Proteins as
Diagnostic Tool in Chronic Myelogenous Leukemia Patients.
AB - More recently, alternative splicing of specific genes are investigated for their
therapeutic potential. In particular, we reported the existence of BCR-ABL
alternative splicing isoforms, in about 80% of Philadelphia-positive patients,
which lead to the expression of aberrant proteins. These fusion proteins are
characterized by an orphan initial and correct Bcr portion attached to a 112
amino acid sequence, arising from the impairment in the reading frame (reading of
ABL exon 4 and 5). We demonstrated that these Abl-out-of-frame (OOF) isoforms
could have an immunological role with therapeutic implications. The aim of this
study was to characterize a new monoclonal antibody (MAb) specific for Abl-OOF
protein portion, for diagnostic use, to detect this biomarker in Philadelphia
chromosome-positive chronic myelogenous leukemia (CML) patients and to generate
novel approaches in the immunotherapy. 5F11G11 MAb recognizes the OOF protein
portion of the native full-length Bcr/Abl-OOF protein expressed in cells
transiently transfected, as demonstrated by immunoprecipitation and
immunofluorescence. In addition, we demonstrate the MAb's ability to recognize
the alternative hybrid Bcr/Abl fusion protein expressed in leukemic cells from
CML patients, to support the possible use of 5F11G11 MAb as a diagnostic tool to
select patients with Philadelphia chromosome-positive CML that could be eligible
for an immunotherapeutic approach with this new antigen.
PMID- 28704166
TI - Give blood today or save lives tomorrow: Matching decision and message construal
level to maximize blood donation intentions.
AB - The research extends construal theory by testing if a match between the temporal
construal framing of a blood donation decision and a blood donation request leads
to higher donation intentions than a mismatch. Results show participants
considering future donation who read an abstract donation request have
significantly higher donation intentions than those who read a concrete request.
Conversely, participants considering donating today who read a concrete donation
request have significantly higher donation intentions than those who read an
abstract request. This study confirms the importance of matching the construal
framing of the communication to the temporal framing of the decision.
PMID- 28704167
TI - "I feel like I've hit the bottom and have no idea what to do": Supportive social
networking on Reddit for individuals with a desire to quit cannabis use.
AB - BACKGROUND: Online communities can provide social support to those in need and
can foster personal empowerment for individuals experiencing distress. This study
examines the content of a Reddit community dedicated to the support of people
trying to quit using cannabis, in order to develop an understanding of the type
of social networking occurring on this subreddit (e.g., community). METHODS: A
total of 100 Reddit posts and their replies (i.e., comments) were collected from
the subreddit on June 12, 2015. Posts were qualitatively coded for expression of
DSM-5 (Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition)
symptoms of cannabis use disorder (CUD) as well as other prominently featured
themes. Comments on posts where individuals were seeking support/advice were also
coded. RESULTS: Ninety-one people posted the 100 Reddit posts, and of those 35
(38%) people described enough symptoms to be classified as mild disorder
severity, 15 (16%) moderate, and 11 (12%) severe, as outlined in the diagnostic
criteria for CUD. Over half of posts (n = 51) were seeking advice and/or support
from members of the community. There were 174 comments made by 108 unique people
on the advice/support seeking posts. Most were supportive/encouraging in nature
(140, 80%) and gave advice to the post author (126, 72%). CONCLUSIONS: This
exploratory research highlights the potential of online communities as tools for
individuals coping with addiction recovery, and future research should
investigate if involvement in such communities would be a beneficial supplement
to more traditional recovery practices.
PMID- 28704168
TI - Integrating Agricultural Injury Prevention with Rural Pediatrics: A Pilot
Assessment.
AB - BACKGROUND: Childhood agricultural injuries are an important public health
problem. Pediatricians are a trusted source of expertise in children's health and
safety and could serve as a sphere of influence to augment child agricultural
injury prevention efforts. The purpose of this pilot study was to begin to
explore the perspectives of pediatricians in a large rural health clinic about
addressing child agricultural injury prevention within their practice. METHODS:
Structured interviews were conducted with nine pediatricians who maintain a
clinical practice of at least 2 days a week and care for newborns through
adolescents. Detailed interviewer notes were reviewed and summarized. RESULTS:
Rural pediatricians readily acknowledge substantial numbers of farm children in
their practice. In general, these providers: (1) recognize farming environments
as a safety risk and see agricultural injury prevention as an important topic to
be addressed with their patients, (2) are comfortable discussing the topic, but
seldom actually initiate such conversations, and (3) doubt farm parents would be
receptive to integrating agricultural injury prevention into a rural pediatric
practice. CONCLUSION: While rural pediatricians recognize child safety risks in
farm environments, they are reluctant to actually initiate this conversation with
parents. Future research should explore both pediatricians' hesitancy to discuss
agricultural injury prevention and farm parents' readiness for integrating the
topic into pediatric primary care visits. Such would help to assess the viability
of pediatricians as a sphere of influence for augmenting child agricultural
injury prevention efforts.
PMID- 28704169
TI - Patients' and clinicians' experiences of wound care in Canada: a descriptive
qualitative study.
AB - OBJECTIVE: This study sought to explore patients' and clinicians' perceptions and
experiences with the provision of standard care by a home care nurse alone or by
a multidisciplinary wound care team. METHOD: The interviews were conducted using
an in-depth semi structured format; following a funnel idea of starting out broad
and narrowing down, ensuring that all the necessary topics were covered by the
end of the interview. RESULTS: A purposive sample of 16 patients with different
wound types were interviewed to ensure that the data would reflect the range and
diversity of treatment and care experience. To reflect the diversity of
experiences 12 clinicians from various clinical backgrounds were interviewed.
Based on the analysis of the interviews, there are four overarching themes: wound
care expertise is required across health-care sectors, psychosocial needs of
patients with chronic wounds are key barriers to treatment concordance,
structured training, and a well-coordinated multidisciplinary team approach.
CONCLUSION: Results of this qualitative study identified different barriers and
facilitators that affect the experiences of community-based wound care.
PMID- 28704170
TI - Expertise by examination: has the experiment failed?
PMID- 28704171
TI - A bioluminescent Pseudomonas aeruginosa wound model reveals increased mortality
of type 1 diabetic mice to biofilm infection.
AB - OBJECTIVE: To examine how bacterial biofilms, as contributing factors in the
delayed closure of chronic wounds in patients with diabetes, affect the healing
process. METHOD: We used daily microscopic imaging and the IVIS Spectrum in vivo
imaging system to monitor biofilm infections of bioluminescent Pseudomonas
aeruginosa and evaluate healing in non-diabetic and streptozotocin-induced
diabetic mice. RESULTS: Our studies determined that diabetes alone did not affect
the rate of healing of full-depth murine back wounds compared with non-diabetic
mice. The application of mature biofilms to the wounds significantly decreased
the rate of healing compared with non-infected wounds for both non-diabetic as
well as diabetic mice. Diabetic mice were also more severely affected by biofilms
displaying elevated pus production, higher mortality rates and statistically
significant increase in wound depth, granulation/fibrosis and biofilm presence.
Introduction of a mutant Pseudomonas aeruginosa capable of producing high
concentrations of cyclic di-GMP did not result in increased persistence in either
diabetic or non-diabetic animals compared with the wild type strain. CONCLUSION:
Understanding the interplay between diabetes and biofilms may lead to novel
treatments and better clinical management of chronic wounds.
PMID- 28704172
TI - Hydroconductive and silver-impregnated foam dressings: a comparison.
AB - OBJECTIVE: As the number of commercially available wound dressings is increasing
rapidly, it is important for clinicians to understand the strengths and
limitations of each and to recognise relationships between wound type and
dressing properties to obtain optimal healing results. Our aim is to test the
antimicrobial activity of two dressings. METHOD: A hydroconductive (HC) dressing
and a silver-impregnated foam (SIF) dressing were compared for their potential to
reduce the levels meticillin-resistant Staphylococcus aureus (MRSA). We also
assessed MRSA-derived biologically active components in liquid or agar matrices,
simplified models for heavily exuding or dry wounds respectively, and in an in
vivo animal model with MRSA infected wounds. RESULTS: In the agar model (dry
wounds) both dressings showed a strong reduction in MRSA activities within 24
hours post-application. The antibacterial effects of the SIF dressing were more
pronounced in the liquid model, however, at an increasing cytotoxic cost. In
agreement with these in vitro results, assessment of dressings using an MRSA
infected wound in an rat model showed a decrease in MRSA which was significant 7
days post-burn and inoculation, with more compromised viability of MRSA.
Dressings showed a similar capability to reduced and eliminate toxic shock
syndrome toxin (TSST-1) at day 7 post-burn in the animal model but not at day 4,
where the SIF dressing was more potent Conclusion: These results confirm the
advantages of using silver in reducing bacterial load in wound treatment, except
for conditions of highly exuding wounds where the cytotoxic properties of silver
may offset these advantages and HC dressing use is more suitable.
PMID- 28704173
TI - Are shame and self-esteem risk factors in prolonged grief after death of a
spouse?
AB - Although many single factors of prolonged grief have been identified in the
literature, a comprehensive understanding of predictors is still lacking. This
article argues that shame and low self-esteem, present risk factors in prolonged
grief after spousal loss, based on a review of correlational studies. Using a
practitioner-scientist approach, a developmental model of shame as a core factor
in prolonged grief is proposed, outlining the progression from childhood
relational trauma, to insecure attachment, shame, self-esteem contingent on
spousal approval to eventual prolonged grief.
PMID- 28704174
TI - Evaluation of pulmonary artery pressure in patients with juvenile systemic lupus
erythematosus (jSLE).
AB - Juvenile systemic lupus erythematosus (jSLE) is a chronic multisystemic
autoimmune disease. Previous studies among adults have shown impaired right
ventricular (RV) function in patients with SLE. Also, these patients may develop
pulmonary artery hypertension (PAH), which is one of the most threatening
complications of SLE. Nevertheless, studies on PAH among jSLE patients are still
rare. The aim of this study was to assess the RV function in jSLE patients by
Doppler echocardiography (Echo Doppler). We also estimated pulmonary artery
systolic pressure (PASP) and mean pulmonary artery pressure (mPAP) in these
patients. A total of 38 jSLE patients and 40 sex- and age-matched controls were
retrospectively analyzed. All patients underwent combined M-mode, cross-sectional
echo, and Doppler Echo examination. The RV function was significantly impaired in
jSLE patients compared to controls. PASP and mPAP were normal in 37 out of 38
patients (97.37%), however, the mean values of PASP and mPAP were significantly
higher in jSLE patients compared to controls (26.90 mmHg versus 21.71 mmHg and
12.63 mmHg versus 9.89 mmHg, respectively) [p < 0.05]. Only one patient (2.6 %)
had elevated mPAP (60 mmHg). The right cardiac catheterization confirmed PAH in
this patient. Although PAH was detected only in one patient, there was a marked
increase of PAP in our jSLE patients. Overall, PASP and mPAP were significantly
higher in jSLE patients compared to healthy controls. Prospective studies with
ethnically diverse cohorts could give more insight on the relevance of PAP and
PHT in patients with jSLE.
PMID- 28704175
TI - Age-Related Differences in Antihypertensive Medication Adherence in Hispanics: A
Cross-Sectional Community-Based Survey in New York City, 2011-2012.
AB - INTRODUCTION: US Hispanics, particularly younger adults in this population, have
a higher prevalence of uncontrolled hypertension than do people of other
racial/ethnic groups. Little is known about the prevalence and predictors of
antihypertensive medication adherence, a major determinant of hypertension
control and cardiovascular disease, and differences between age groups in this
fast-growing population. METHODS: The cross-sectional study included 1,043
community-dwelling Hispanic adults with hypertension living in 3 northern
Manhattan neighborhoods from 2011 through 2012. Age-stratified analyses assessed
the prevalence and predictors of high medication adherence (score of 8 on the
Morisky Medication Adherence Scale [MMAS-8]) among younger (<60 y) and older
(>=60 y) Hispanic adults. RESULTS: Prevalence of high adherence was significantly
lower in younger versus older adults (24.5% vs 34.0%, P = .001). In younger
adults, heavy alcohol consumption, a longer duration of hypertension, and recent
poor physical health were negatively associated with high adherence, but poor
self-rated general health was positively associated with high adherence. In older
adults, advancing age, higher education level, high knowledge of hypertension
control, and private insurance or Medicare versus Medicaid were positively
associated with high adherence, whereas recent poor physical health and health
related activity limitations were negatively associated with high adherence.
CONCLUSION: Equitable achievement of national hypertension control goals will
require attention to suboptimal antihypertensive medication adherence found in
this study and other samples of US Hispanics, particularly in younger adults. Age
differences in predictors of high adherence highlight the need to tailor efforts
to the life stage of people with hypertension.
PMID- 28704176
TI - Availability and Promotion of Healthful Foods in Stores and Restaurants - Guam,
2015.
AB - Chronic disease, which is linked to unhealthy nutrition environments, is highly
prevalent in Guam. The nutrition environment was assessed in 114 stores and 63
restaurants in Guam. Stores had limited availability of some healthier foods such
as lean ground meat (7.5%) and 100% whole-wheat bread (11.4%), while fruits
(81.0%) and vegetables (94.8%) were more commonly available; 43.7% of restaurants
offered a healthy entree or main dish salad, 4.1% provided calorie information,
and 15.7% denoted healthier choices on menus. Improving the nutrition environment
could help customers make healthier choices.
PMID- 28704177
TI - Morphology and contractile gene expression of adipose-derived mesenchymal stem
cells in response to short-term cyclic uniaxial strain and TGF-beta1.
AB - Previous studies have shown smooth muscle induction in adipose-derived
mesenchymal stem cells (ASCs) caused by long-term cyclic stretch. Here we
examined the capability of the short-term straining with time steps of 4, 8, 16
and 24 h alone or combined with TGF-beta1 on smooth muscle induction of rabbit
ASCs. Alterations in cell morphology were quantified through the cell shape index
and orientation angle, and expression levels of alpha-SMA, SM22-alpha, h
caldesmon and calponin3 markers were examined using the real-time polymerase
chain reaction (PCR) method. Moreover, F-actin cytoskeleton organization was
observed by fluorescence staining. Mechanical strain either alone or combined
with growth factor treatment caused significant up-regulation of both early and
intermediate smooth muscle cells (SMCs) specific markers during the initial hours
of stimulation peaking in 8 to 16 h. Furthermore, gradual alignment of cells
perpendicular to the strain direction during loading time, and cell elongation
resembling contractile SMC phenotype, together with alignment and reorganization
of F-actin fibers were observed. Considering previously reported protein up
regulation in following days of straining, the effects of short-term cyclic
stretch on smooth muscle induction of ASCs were revealed which can be helpful in
achieving functional contractile SMCs through synergistic mechano-chemical
regulation of ASCs as an appealing cell source for vascular tissue engineering.
PMID- 28704178
TI - Determination of serum calcium levels by 42Ca isotope dilution inductively
coupled plasma mass spectrometry.
AB - BACKGROUND: Serum calcium level is an important clinical index that reflects
pathophysiological states. However, detection accuracy in laboratory tests is not
ideal; as such, a high accuracy method is needed. METHODS: We developed a
reference method for measuring serum calcium levels by isotope dilution
inductively coupled plasma mass spectrometry (ID ICP-MS), using 42Ca as the
enriched isotope. Serum was digested with 69% ultrapure nitric acid and diluted
to a suitable concentration. The 44Ca/42Ca ratio was detected in H2 mode; spike
concentration was calibrated by reverse IDMS using standard reference material
(SRM) 3109a, and sample concentration was measured by a bracketing procedure. We
compared the performance of ID ICP-MS with those of three other reference methods
in China using the same serum and aqueous samples. RESULTS: The relative expanded
uncertainty of the sample concentration was 0.414% (k=2). The range of
repeatability (within-run imprecision), intermediate imprecision (between-run
imprecision), and intra-laboratory imprecision were 0.12%-0.19%, 0.07%-0.09%, and
0.16%-0.17%, respectively, for two of the serum samples. SRM909bI, SRM909bII,
SRM909c, and GBW09152 were found to be within the certified value interval, with
mean relative bias values of 0.29%, -0.02%, 0.10%, and -0.19%, respectively. The
range of recovery was 99.87%-100.37%. Results obtained by ID ICP-MS showed a
better accuracy than and were highly correlated with those of other reference
methods. CONCLUSIONS: ID ICP-MS is a simple and accurate candidate reference
method for serum calcium measurement and can be used to establish and improve
serum calcium reference system in China.
PMID- 28704179
TI - Analytical evaluation of the new Beckman Coulter Access high sensitivity cardiac
troponin I immunoassay.
AB - BACKGROUND: This study was aimed to evaluate the analytical performance of the
novel chemiluminescent and fully-automated Beckman Coulter Access hsTnI high
sensitivity immunoassay for measurement of cardiac troponin I (cTnI). METHODS:
The study, using lithium heparin samples, included assessment of limit of blank
(LOB), limit of detection (LOD), functional sensitivity, linearity, imprecision
(within run, between-run and total), calculation of 99th percentile upper
reference limit (URL) in 175 healthy blood donors (mean age, 36+/-12 years; 47%
women) and comparison with two other commercial cTnI immunoassays. RESULTS: The
LOB, LOD and functional sensitivity of Access hsTnI were 0.14, 0.34 and 1.35
ng/L, respectively. The within-run, between-run and total imprecision was 2.2%
2.9%, 4.6%-5.4%, and 5.4%-6.1%, respectively. The linearity was excellent in the
range of cTnI values between 0.95 and 4195 ng/L (r=1.00). The 99th percentile URL
was 15.8 ng/L. Measurable cTnI values were found in 173/175 healthy subjects
(98.9%). Good agreement of cTnI values was found with AccuTnI+3 (r=0.97; mean
bias, -9.3%), whereas less satisfactory agreement was found with Siemens
Dimension Vista cTnI (r=0.95; mean bias, -55%). CONCLUSIONS: The results of our
evaluation of the Beckman Coulter Access hsTnI indicate that the analytical
performance of this fully-automated immunoassay is excellent.
PMID- 28704180
TI - Placental protein-13 (PP13) in combination with PAPP-A and free leptin index
(fLI) in first trimester maternal serum screening for severe and early
preeclampsia.
AB - BACKGROUND: Placental protein-13 (PP13) is involved in placental invasion and has
been suggested as a maternal serum marker of preeclampsia (PE) development.
However, the discriminatory ability of PP13 in first trimester has not been
completely clarified. METHODS: PP13 was measured in first trimester (week 10+3
13+6) maternal serum from 120 PE pregnancies and 267 control pregnancies and was
correlated with clinical parameters. The population screening performance of PP13
in combination with the PE markers pregnancy associated plasma protein A (PAPPA)
and free leptin index (fLI) was assessed by Monte Carlo simulation. RESULTS: In
severe PE (including HELLP) cases (n=26) the median PP13 concentration was 35.8
pg/mL (range: 17.8-85.5 pg/mL) and in PE pregnancies (n=10) with birth prior to
week 34, the median PP13 concentration was 30.6 pg/mL (13.1-50.1 pg/mL), compared
to controls with a median of 54.8 pg/mL (range: 15.4-142.6 pg/mL) (p<0.04). The
population screening detection rate (DR) for a false-positive rate of 10% for
severe PE and HELLP was 26% for PP13, 28% for PP13+PAPP-A, 33% for PP13+fLI, and
40% for PP13+PAPP-A+fLI. CONCLUSIONS: PP13 is a marker of severe PE and HELLP
syndrome. The screening performance of PP13 can be markedly improved by combining
it with fLI and PAPP-A.
PMID- 28704181
TI - The Impact of Hyperglycemia on VEGF Secretion in Retinal Endothelial Cells.
AB - BACKGROUND: Diabetic retinopathy is a serious sight-threatening complication
which is manifested by excessive angiogenesis in diabetic patients. AIM: We
hypothesize that cultured Rhesus monkey retinal endothelial cells (RhRECs)
respond to high glucose with a change in cell proliferation and vascular
endothelial growth factor (VEGF) secretion. MATERIALS AND METHODS: In our study,
20 000 cells per well were treated without glucose or with 5.5 mM, 18.5 mM and 30
mM glucose for 24 hours. Viable cells were counted using trypan blue dye
exclusion method. VEGF concentrations were measured in cell media by ELISA
method. RESULTS: The number of viable cells incubated with 5.5 mM glucose
increased significantly by 53.7% after 24 hours. In comparison, the number of
viable cells decreased by 2.8% at 18.5 mM of glucose and by 20.4% at 30 mM of
glucose after 24 hours of incubation. In contrast to this effect of glucose on
the number of viable cells, a significant increase in VEGF levels (pg/mL) in the
cell media with a glucose concentration of 0 mM compared to 5.5 mM of glucose was
found. VEGF secretion in cell medium with 18.5 and 30 mM of glucose increased non
significantly in comparison with euglycemic levels. CONCLUSION: Our results show
that viability of retinal endothelial cells and VEGF release are highly
responsive to changes in glucose concentration. Such glucose-induced changes in
retinal endothelial cells may negatively impact the integrity of the
microvasculature in the diabetic retina leading to angiogenesis and
microaneursym.
PMID- 28704182
TI - Chronic Obstructive Pulmonary Disease and Hepatitis C.
AB - Chronic obstructive pulmonary disease (COPD) is a preventable, treatable disease
with significant extrapulmonary manifestations that could affect negatively its
course in some patients. Hepatitis C virus infection (HCV), on the other hand, is
associated with a number of extrahepatic manifestations. COPD patients have
increased prevalence of HCV and patients with HCV, especially older ones, have
increased prevalence and faster progression of COPD. HCV infection exerts long
term effects on lung tissue and is an additional risk factor for the development
of COPD. The presence of HCV is associated with an accelerated loss of lung
function in COPD patients, especially in current smokers. COPD could represent
extrahepatic manifestation associated with HCV infection. The aim of this article
was to review the literature on prevalence of HCV in COPD and vice versa,
pathogenetic link and the consequences of their mutual existence.
PMID- 28704183
TI - Simultaneous Abdominoplasty and Umbilical Hernia Repair via Laparoscopy: a
Preliminary Report.
AB - BACKGROUND: Umbilical hernias (UH) are common in postpartum patients seeking
abdominal contouring surgery and the question of simultaneous abdominoplasty and
UH repair is raised. This presents, however, a risk to the umbilicus
vascularisation with possible umbilical necrosis. To minimize this risk we
associated abdominoplasty with laparoscopic UH repair. The aim of this study was
to present the technique of simultaneous abdominoplasty and UH repair and the
first results. MATERIALS AND METHODS: Simultaneous abdominoplasty and
laparoscopic mesh UH repair was analysed in the first 10 cases. The intervention
was performed by a plastic surgeon and a general surgeon. It begins as a standard
abdominoplasty with flap elevation, umbilicus detachment and diastasis repair, if
indicated. The second stage is the UH repair via laparoscopy using an
intraperitoneal mesh. The third stage consists of umbilical transposition and
closure of the abdominoplasty incision. RESULTS: We had no complications at the
umbilicus or the hernia mesh. In all cases, umbilical vascularisation was
preserved and no hernia recurrence was noted. CONCLUSIONS: Our first results
suggest that the simultaneous UH repair with abdominoplasty is safe, minimizing
the risk to the umbilicus blood supply. These first results encourage us to
recommend this approach and perform a more detailed analysis of the whole series
since our first case.
PMID- 28704184
TI - Enzymatic Hydrolysis of Water Extractable Polysaccharides from Leaves of Plantago
major L.
AB - BACKGROUND: Plantago major L. leaves have been used for centuries by the
traditional medicine in the treatment of infectious disorders of the respiratory,
urinary and digestive tracts. Researchers have reported that hot water extracts
of Plantago major possess a broad-spectrum of anticancer, antioxidant and
antiviral activities, as well as activities which modulate cell-mediated
immunity. Their beneficial properties may be due to the significant content of
polysaccharides. The polysaccharides that have been isolated from the leaves of
Plantago major L. have different structures - pectic substances, galactans,
arabinogalactans, glucomannans. AIM: The aim of this paper was to study the
correlation between the structure of the water extractable polysaccharides
isolated from Plantago major L. leaves and their enzymatic hydrolysis with
different carbohydrate hydrolases. MATERIALS AND METHODS: The hydrolysis
reactions were performed with the enzymes hemicellulase and mannanase.
Spectrophotometric total reducing sugars assay was used to examine the hydrolysis
yield. The monosaccharide and oligosaccharide compositions were determined using
HPLC analysis. RESULTS: The highest hydrolysis yield of the water extractable
polysaccharides from Plantago major leaves was obtained by treatment with
hemicellulase. The hydrolysis yield increased with the augmentation of the ratio
of enzyme to polysaccharide. Galactose was the prevalent monosaccharide
identified in the composition of the isolated polysaccharides. Oligosaccharides
with different degree of polymerization were also detected. CONCLUSION: The
enzymatic hydrolysis of water extractable polysaccharides from Plantago major
leaves allows us to obtain different types of oligosaccharides with beneficial
effects on both human health and industry.
PMID- 28704185
TI - Phenotypes Determined by Cluster Analysis in Moderate to Severe Bronchial Asthma.
AB - BACKGROUND: Bronchial asthma is a heterogeneous disease that includes various
subtypes. They may share similar clinical characteristics, but probably have
different pathological mechanisms. AIM: To identify phenotypes using cluster
analysis in moderate to severe bronchial asthma and to compare differences in
clinical, physiological, immunological and inflammatory data between the
clusters. PATIENTS AND METHODS: Forty adult patients with moderate to severe
bronchial asthma out of exacerbation were included. All underwent clinical
assessment, anthropometric measurements, skin prick testing, standard spirometry
and measurement fraction of exhaled nitric oxide. Blood eosinophilic count, serum
total IgE and periostin levels were determined. Two-step cluster approach,
hierarchical clustering method and k-mean analysis were used for identification
of the clusters. RESULTS: We have identified four clusters. Cluster 1 (n=14) -
late-onset, non-atopic asthma with impaired lung function, Cluster 2 (n=13) -
late-onset, atopic asthma, Cluster 3 (n=6) - late-onset, aspirin sensitivity,
eosinophilic asthma, and Cluster 4 (n=7) - early-onset, atopic asthma.
CONCLUSIONS: Our study is the first in Bulgaria in which cluster analysis is
applied to asthmatic patients. We identified four clusters. The variables with
greatest force for differentiation in our study were: age of asthma onset,
duration of diseases, atopy, smoking, blood eosinophils, nonsteroidal anti
inflammatory drugs hypersensitivity, baseline FEV1/FVC and symptoms severity. Our
results support the concept of heterogeneity of bronchial asthma and demonstrate
that cluster analysis can be an useful tool for phenotyping of disease and
personalized approach to the treatment of patients.
PMID- 28704186
TI - Comparative Characteristics of Napsin A, TTF 1 and EGFR Mutation Expression in
Mucinous Lung Cell Carcinomas.
AB - BACKGROUND: Invasive mucinous lung adenocarcinomas are rare and account for 2%
10% of all lung adenocarcinoma cases. It is believed that Napsin A exhibits a
weaker expression in mucinous adenocarcinomas compared with TTF1, but such
correlation is still poorly researched. AIM: The aim of the study was to
determine the frequency of mucinous to nonmucinous adenocarcinomas and compare
specificity and sensitivity of monoclonal Napsin A with TTF1 in mucinous
adenocarcinomas and define the frequency of EGFR mutations. MATERIALS AND
METHODS: Eighty-four resected lung carcinomas were prospectively evaluated. All
biopsies were analysed with p63, TTF1, monoclonal Napsin A, CK7, CK20 and CDX2
and were studied with real-time PCR technology. RESULTS: In resected material we
detected 49/84 (58.3%) adenocarcinomas and selected 21 mucinous adenocarcinomas
out of 46 non-mucinous adenocarcinomas (45.6%). The most common pattern of
mucinous adenocarcinomas is papillary - 24% and colloidal - 24%, followed by
acinar - 19.2% and lepidic - 19.2%. mNapsin A was positive in 18/21 (85.7%)
mucinous adenocarcinomas v/s 17/21 TTF1 positive (80.9%). EGFR mutations were
detected in 3/21 cases with mucinous adenocarcinomas (14.3%): mucinous papillary,
mucinous acinar and "salivary gland-like". CONCLUSION: Our study demonstrates a
high proportion of primary mucinous lung adenocarcinomas to primary non-mucinous
adenocarcinomas. Sensitivity and specificity of mNapsin A and TTF1 did not show
significant difference in pulmonary mucinous and non-mucinous adenocarcinomas, as
mNapsin A gave greater sensitivity to mucinous adenocarcinomas. Our results
indicate the same mutation frequency of EGFR in mucinous adenocarcinomas as
mutation frequency detected in non-mucinous adenocarcinomas in the Bulgarian
region.
PMID- 28704187
TI - Striving for Better Medical Education: the Simulation Approach.
AB - Medical simulation is a rapidly expanding area within medical education due to
advances in technology, significant reduction in training hours and increased
procedural complexity. Simulation training aims to enhance patient safety through
improved technical competency and eliminating human factors in a risk free
environment. It is particularly applicable to a practical, procedure-orientated
specialties. Simulation can be useful for novice trainees, experienced clinicians
(e.g. for revalidation) and team building. It has become a cornerstone in the
delivery of medical education, being a paradigm shift in how doctors are educated
and trained. Simulation must take a proactive position in the development of
metric-based simulation curriculum, adoption of proficiency benchmarking
definitions, and should not depend on the simulation platforms used. Conversely,
ingraining of poor practice may occur in the absence of adequate supervision, and
equipment malfunction during the simulation can break the immersion and disrupt
any learning that has occurred. Despite the presence of high technology, there is
a substantial learning curve for both learners and facilitators. The technology
of simulation continues to advance, offering devices capable of improved fidelity
in virtual reality simulation, more sophisticated procedural practice and
advanced patient simulators. Simulation-based training has also brought about
paradigm shifts in the medical and surgical education arenas and ensured that the
scope and impact of simulation will continue to broaden.
PMID- 28704188
TI - Effect of Extracts of Bilberries (Vaccinium myrtillus L.) on Amyloglucosidase and
alpha-Glucosidase Activity.
AB - BACKGROUND: Vaccinium myrtillus L. is a species belonging to the genus Vaccinium
of the family Ericaceae. Bilberries have drawn attention due to the multiple
benefits for the human health, including antioxidant, anti-inflammatory,
anticancer, anti-neurodegenerative, and cardioprotective effects. Recently,
bilberries were shown to inhibit the activity of carbohydrate-hydrolysing enzymes
that can help reduce the intensity of the metabolic syndrome and prevent type 2
diabetes. AIM: In this study, we investigated the alpha-glucosidase and
amyloglucosidase inhibitory activities of polyphenol-rich extracts from fruit of
Vaccinium myrtillus L. from different regions in Bulgaria. MATERIALS AND METHODS:
The total phenolic content was determined spectrophotometrically using the Folin
Ciocalteu method. With HPLC analysis, phenolic acid composition of extracts was
assessed. Enzymatic inhibitory activities were determined according to the
methodology by Borooah et al. (1961), and Dewi et al. (2007). Amyloglucosidase
assay and alpha-glucosidase assay were used to measure the inhibition potential
of bilberries' extracts. RESULTS: Phenolic compound content ranged from 1299.60
mg to 510.88 mg GAE/100 g for organic extracts and from 453.63 mg to 290.83 mg
GAE/100 g for aqueous extracts. Based on qualitative HPLC analyses, gallic acid
and chlorogenic acid were found to be among the major phenolic acids present in
bilberries. Methanol and aqueous extracts there were found to be effective
inhibitors of alpha-glucosidase with an IC50 value of 20 MUg GAE/ml and 55 MUg
GAE/ml, respectively. CONCLUSION: The inhibitory activity of bilberries' extracts
towards alpha-glucosidase offers the patients with type 2 diabetes the
opportunity to manage their own glycaemic levels with a diet.
PMID- 28704189
TI - Chronic Hepatitis Due to Gluten Enteropathy - a Case Report.
AB - BACKGROUND: Celiac disease is an immune-mediated enteropathy precipitated by
exposure to dietary gluten in genetically predisposed individuals. CASE
DESCRIPTION: A 45-year-old Caucasian woman presented with severe iron-deficient
anemia and mild elevation of liver enzymes. Upper endoscopy was done in the
context of evaluation of anemia, which revealed reduced duodenal folds and mosaic
pattern of the mucosa, but also grade II esophageal varices and portal
hypertensive gastropathy. Duodenal biopsy showed total villous atrophy, diffuse
mainly lymphocytic infiltrate, presence of intra-epithelial lymphocytes. Serology
test confirmed celiac disease by the typical pattern of high titer positive IgA
and IgG antibodies to tissue transglutaminase. Liver biopsy was performed for
staging and etiological evaluation, because laboratory screening ruled out common
viral, metabolic and autoimmune liver disease. Liver morphology was consistent
with chronic hepatitis without findings for extensive fibrosis. Our patient had
poor dietary compliance, so we failed to established improvement of liver enzymes
and resolution of anemia during follow-up. CONCLUSIONS: We would like to stress
on the diverse clinical manifestations of celiac disease and the importance of
serologic screening with antibodies to tissue transglutaminase in differential
diagnosis of chronic liver disease.
PMID- 28704190
TI - Modulating Effects of Cholecalciferol Treatment on Estrogen Deficiency-Induced
Anxiety-Like Behavior of Adult Female Rats.
AB - BACKGROUND: Vitamin D can be one of the candidate substances that are used as
additional supplementation in the treatment of anxiety-related disorders in women
with estrogen imbalance. MATERIALS AND METHODS: The aim of the present study was
to examine the effects of chronic cholecalciferol administration (1.0, 2.5 or 5.0
mg/kg/day, s.c.) on the anxiety-like behavior and monoamines levels in the rat
hippocampus following ovariectomy in female rats. Cholecalciferol was given to
ovariectomized (OVX) rats and OVX rats treated with 17beta-estradiol (17beta-E2,
0.5 MUg/rat, s.c.). The anxiety-like behavior was assessed in the elevated plus
maze (EPM) and the light-dark tests (LDT), locomotor and grooming activities were
assessed in the open-field test (OFT). RESULTS: Cholecalciferol in high doses
alone or in combination with 17beta-E2-induced anxiolytic-like effects in OVX and
OVX rats treated with 17beta-E2 as evidenced in the EPM and LDT tests, and
increased grooming activity in the OFT test. We found that DA and 5-HT levels
increased while 5-HT turnover in the hippocampus decreased in these groups of OVX
rats. CONCLUSION: Our results indicate that cholecalciferol in high doses has a
marked anxiolytic-like effect due to an increase in the monoamines levels in the
experimental rat model of estrogen deficiency.
PMID- 28704191
TI - Association of Permeability and Lipid Content of Membrane.
AB - BACKGROUND: Rat skin and goat cul de sac are mostly used in optimization of
formulations as the model of human skin and cul de sac. AIM: To explore the
correlation between lipid content of rat skin and goat cul de sac and
permeability. MATERIALS AND METHODS: Find out wavelength maximum for Sapat plus
malam(r), Ciplox eye ointment(r) and chloramphenicol eye caps and the standard
curve was also derived. In vitro studies using Cellophane(r) membrane and ex vivo
studies using rat skin or goat cul de sac of the formulations. Permeability
coefficient, % dislodgeable dose, lag time, diffusion parameter, and partition
coefficient were found for both studies after six and a half hours of penetration
studies. Student's unpaired t-test with equal variance was used to find any
statistically significant difference in the ex vivo and in vitro diffusion
transport studies at 95% level of confidence. RESULTS: Permeability coefficient
of Sapat plus malam(r), Ciplox eye ointment(r) and chloramphenicol eye caps were
0.000316 +/- 0.0000625, 0.00416 +/- 0.0001, 0.0034 +/- 0.00004 for Cellophane(r)
membrane and 0.0001 +/- 0.000001, 0.002254 +/- 0.0002, 0.00303 +/- 0.0001 for ex
vivo membrane in cm2/min, respectively. For all three formulations, there were
calculated t values which were higher than tabulated t values at 95% of
confidence level (P<0.05). CONCLUSION: Cellophane(r) membrane shows a better
diffusion than rat skin or goat cul de sac. In the optimization of formulation,
only Cellophane(r) membrane is advisable to use.
PMID- 28704192
TI - Risk Factors for Postpartum Thyroid Dysfunction in Euthyroid Women Prior to
Pregnancy.
AB - BACKGROUND: Thyroid dysfunction is common during the postpartum and the
predisposing factors for its development are considered specific for the
population studied. The aim of this study was to evaluate the risk factors for
the occurrence of postpartum thyroid dysfunction (PPTD) in euthyroid women prior
to pregnancy. MATERIALS AND METHODS: Forty-five women with PPTD and 55 age
matched euthyroid postpartum women from Plovdiv, Bulgaria were included in the
study. TSH, FT4, FT3, TPOAb, TgAb, TRAb were measured and ultrasound evaluation
of the thyroid was performed in the first trimester of pregnancy and during the
postpartum. RESULTS: The study found higher risk of developing PPTD in women with
family history of thyroid disease (OR 4.42; 95% CI 1.87,10.43), smokers (OR 4.01;
95% CI 1.72,9.35), personal history of autoimmune thyroid disease (OR 5.37; 95%
CI 1.15,28.53), positive TPOAb (OR 18.12; 95% CI 4.93,66.65) and thyroid US
hypoechogenicity during early pregnancy (OR 6.39; 95% CI 2.53,16.12) and those
who needed levothyroxine during pregnancy (OR 3.69; 95% CI 1.28,10.61). BMI
before pregnancy was significantly lower in women with PPTD than in euthyroid
postpartum women (22.80+/-0.55 vs 26.25+/-0.97, p=0.013). The multivariate
logistic regression analysis identified as most important independent risk
factors for PPTD occurrence the TPOAb positivity during early pregnancy, family
history of thyroid disease, smoking and lower BMI before pregnancy. CONCLUSION:
Our data suggest that in the population studied several factors are associated
with an increased risk of PPTD and screening for thyroid disorders among those
women can be beneficial.
PMID- 28704193
TI - Rehabilitation of Patients with Hip Joint Arthroplasty (Late Post-surgery Period
Hospital Rehabilitation).
AB - BACKGROUND: Hip joint replacement (endoprosthesis, alloplasty) has become one of
the most frequent surgery interventions of the 20th century. AIM: To conduct
rehabilitation therapy in the late post-surgery period of hospital rehabilitation
(45 days after surgery), to track patients' progress and measure the results.
MATERIALS AND METHODS: One hundred and fifty-two patients with hip joint
endoprosthesis were included in the study. All underwent surgery and
rehabilitation at the Department of Clinical Rehabilitation of the Physical and
Rehabilitation Medicine Clinic at Doctor G. Stranski University Hospital, Pleven.
Kinesitherapy included therapeutic massage, isometric exercises for gluteal and
hip muscles, isotonic exercises for the hip and the knee joint, breathing
exercises, analytical gymnastics, exercises for balance and posture stability;
gait control, exercises with gym equipment; occupational exercises included all
activities of daily living (ADL) that were practiced at home; treatment with
performed physical factors included applying magnetic field, interferential
current therapy, electrostimulation of the m. quadriceps femoris and the gluteal
muscles. RESULTS: The scores from the pain visual analog scale (VAS), the muscle
strength test and the test for the movement volume of the hip joint were obtained
at the beginning and at the end of the rehabilitation process and stored in an
individual file for each patient. CONCLUSION: The results of the present study
suggest that the complex rehabilitation program (kinesitherapy, performed
physical factors and occupational therapy) can result in a considerably faster
recovery and ensures that patients reach optimal functional results.
PMID- 28704194
TI - Sarcomatoid Squamous Cell Carcinoma of the Penis - a Report of Two Cases.
AB - BACKGROUND: Sarcomatoid (spindle cell) squamous cell carcinoma is a rare,
highgrade, aggressive tumor consisting of the squamous cell carcinoma admixed
with the malignant spindle cell (sarcomatoid) elements. These tumors are
relatively uncommon in the genitourinary system and particularly in the penis.
MATERIALS AND METHODS: Two sarcomatoid squamous cell carcinomas of the penis were
diagnosed in our hospital between 2012 and 2015. Clinical histories, pathology
reports, hematoxylin and eosin-stained and immunohistochemical slides were
reviewed. RESULTS: In both cases, the tumors presented as single, pedunculated,
extensive masses with surface ulceration; histology study showed a mixture of
high-grade squamous cell carcinoma component and spindle cell neoplastic
component in different proportions. Immunohistochemical stains of CK AE1/AE3, p63
and CK903 showed positive immunoreactivity in both components in both cases.
Vimentin was positive in spindle cell component and negative in squamous cell
carcinoma areas. CONCLUSION: Sarcomatoid squamous cell carcinoma of the penis is
an uncommon tumor of this site with aggressive behavior and bad prognosis which
might be related to the delay in medical examination and diagnosis. A correct and
thorough morphological study is of great importance for the staging of the
disease, treatment and follow up of patients.
PMID- 28704195
TI - Association between Type 2 Diabetes, Obesity and Key Immunological Components of
IgE-mediated Inflammation.
AB - BACKGROUND: Changes in lifestyle and obesity in recent decades have brought about
a dramatic increase in type 2 diabetes mellitus (DM2) and allergic diseases.
Clinical and epidemiological studies associate obesity with epidemics of allergic
diseases. The link between obesity and DM2 with immunological components of IgE
mediated allergic inflammation is not yet conclusively established. AIM: To
examine the key immunological components of IgE-mediated allergic inflammation in
patients with DM2 and their relationship with glycemic control and anthropometric
indicators. MATERIALS AND METHODS: Fifty-five patients with DM2 and 32 healthy
controls with normal weight and body mass index (BMI) of 18-24.9 kg/m2 were
included in the study. Th2-cytokine profile (serum levels of IL-4 and IL-5,
pg/ml) and total serum IgE IU/ml were assessed in all participants in the study
using ELISA. In patients with DM2, levels of glycated hemoglobin (HbA1c%) in the
blood were also measured. RESULTS: Serum levels of IL-4 and IL-5 are
significantly higher in patients with DM2 compared to the control group. Serum
levels of IL-4 and IL-5 positively correlated with BMI as well as serum levels of
IL-4 with waist circumference. Total serum IgE positively correlated with HbA1c.
CONCLUSION: Obesity and poor glycemic control in patients with DM2 affect key
immunological components of IgE-mediated allergic inflammation and possibly alter
the immune response to allergens and antigens.
PMID- 28704196
TI - Antioxidant capacity and phenolic content of two Algerian Mentha species M.
rotundifolia (L.) Huds, M. pulegium L., extracted with different solvents.
AB - Background It is important to consider the optimum conditions and processing
factors (like solvent type) influencing activity of plant antioxidants for
utilization in food and biological systems. Methods The antioxidant capacity and
phenolic content of two Mentha species, namely, Mentha pulegium L. (MP) and
Mentha rotundifolia (L.) Huds (MR), were studied and six solvent systems were
used. The total antioxidant capacity of the mint species extracts was evaluated
using phosphomolybdenum method and the free radical-scavenging capacity by 2,2
diphenyl-1-picrylhydrazyl radical-scavenging assay. Results The efficiency of the
used solvents to extract phenols from the two species varied considerably. The
highest total phenolic content was obtained from methanol extract of MP (25.3+/
1.3 mg GAE/gdw) and total flavonoid content from methanol extract of MR (10.1+/
0.1 mg QE/gdw). High phenol content was significantly correlated with high
antioxidant capacity. The methanol extracts showed the highest radical scavenging
activity. All the extracts showed variable antioxidant capacity by the formation
of phosphomolybdenum complex. Acetone extract of MP and methanol extract of MR
exhibited marked reducing power in this method. Conclusions Our findings
identified the appropriate solvent for extracting MP and MR phenolics which might
provide a rich source of natural antioxidants.
PMID- 28704197
TI - Expectant management in di-chorionic pregnancies complicated by discordant
anomalous twin.
PMID- 28704198
TI - Alzheimer's disease: as it was in the beginning.
AB - Since Alzheimer's disease was first described in 1907, many attempts have been
made to reveal its main cause. Nowadays, two forms of the disease are known, and
while the hereditary form of the disease is clearly caused by mutations in one of
several genes, the etiology of the sporadic form remains a mystery. Both forms
share similar sets of neuropathological and molecular manifestations, including
extracellular deposition of amyloid-beta, intracellular accumulation of
hyperphosphorylated tau protein, disturbances in both the structure and functions
of mitochondria, oxidative stress, metal ion metabolism disorders, impairment of
N-methyl-D-aspartate receptor-related signaling pathways, abnormalities of lipid
metabolism, and aberrant cell cycle reentry in some neurons. Such a diversity of
symptoms led to proposition of various hypotheses for explaining the development
of Alzheimer's disease, the amyloid hypothesis, which postulates the key role of
amyloid-beta in Alzheimer's disease development, being the most prominent.
However, this hypothesis does not fully explain all of the molecular
abnormalities and is therefore heavily criticized. In this review, we propose a
hypothetical model of Alzheimer's disease progression, assuming a key role of age
related mitochondrial dysfunction, as was postulated in the mitochondrial cascade
hypothesis. Our model explains the connections between all the symptoms of
Alzheimer's disease, with particular attention to autophagy, metal metabolism
disorders, and aberrant cell cycle re-entry in neurons. Progression of the
Alzheimer's disease appears to be a complex process involving aging and too many
protective mechanisms affecting one another, thereby leading to even greater
deleterious effects.
PMID- 28704199
TI - The role of ubiquitin proteasomal system and autophagy-lysosome pathway in
Alzheimer's disease.
AB - Alzheimer's disease (AD) is the most common neurodegenerative disorder leading to
dementia in the elderly population. AD is associated with the buildup of beta
amyloid and tau, which aggregate into extracellular plaques and neurofibrillary
tangles. Although the exact mechanism of pathological process of AD is unclear,
the dysfunction of protein degradation mechanisms has been proposed to play an
important role in AD. The cellular degradation of abnormal or misfolded proteins
consists of three different mechanisms: the ubiquitin proteasomal system (UPS),
autophagy-lysosomal pathway (ALP), and interaction of molecular chaperones with
UPS or ALP. Any disturbance to these systems causes proteins to accumulate,
resulting in pathological process of AD. In this review, we summarize the
knowledge of protein degradation pathways in the pathogenesis of AD in light of
the current literature. In the future, the regulation UPS or ALP machineries
could be the cornerstones of the treatment of AD.
PMID- 28704200
TI - Mild cognitive impairment in type 2 diabetes mellitus and related risk factors: a
review.
AB - Type 2 diabetes mellitus (T2DM) is a global epidemic disease and has become a
significant health problem. Many studies have raised concern about the mild
cognitive impairment (MCI) with T2DM and even the Alzheimer's disease patients
with T2DM. The incidence of MCI is higher in individuals with T2DM than those
without diabetes. Cognitive changes might affect everyday activities depending on
the work and situation. Although the exact pathophysiology of MCI in T2DM is
unclear, many studies suggest that the alterations in pathoglycemia, diabetic
complications, related end products, and physical/psychological status are
significant risk factors. In this article, we systematically overview the studies
to illustrate the related risk factors of cognitive impairment in patients with
T2DM. Further high quality studies and treatment need to be initiated and it will
become incumbent on clinicians to identify and cure the earliest signs of
clinical impairment.
PMID- 28704201
TI - IL-17 and Th17 cells in systemic sclerosis: a comprehensive review.
AB - T cells (especially T helper cells) seem to be strongly associated with systemic
sclerosis pathogenesis. Th17-IL-17 axis was proved to be involved in the
pathogenesis of multiple autoimmune diseases. By performing a comprehensive
research of the literature indexed in PubMed database, the current review
summarizes current knowledge related to Th17 and IL-17 in systemic sclerosis.
While there is promising data suggesting inhibition of Tregulatory and Th1
signals on one hand and promotion of Th17 and Th2 signals on the other, studies
that include prospective and integrated analysis of Tregulatory, Th17, Th1, Th2
(cells and derived cytokines) on the same cohort of Ssc patients are warranted.
PMID- 28704202
TI - The integration of the molecular methods in the diagnosis algorithm for the
poliovirus detection in the sewage water: comparing concentration and detection
methods. A Pilot Study.
AB - INTRODUCTION: Two cases of circulating vaccine-derived poliovirus type 1(cVDPV1),
from southwestern Ukraine, bordering Romania, were confirmed in 2015 and the
environmental enterovirus surveillance was enhanced in our country. The molecular
detection of human enteroviruses as a screening test followed by isolation on
cell culture lines or sequencing could be proposed as a new diagnosis algorithm.
MATERIAL AND METHODS: The sensitivity of two molecular methods for the detection
of enterovirus strains in 10 mL of sewage water (15 samples) was studied with
Film Array ME panel BioFire (Biomerieux, France) and Xpert EV assay (Cepheid,
USA). These are standardized methods for the detection of microorganisms in the
cerebrospinal fluid (CSF). RESULTS: Of the 15 samples, six enterovirus strains
were detected using Film Array ME, four enterovirus strains were detected using
Xpert EV assay, while only two nonpolio enterovirus strains were isolated on RD
cell line, using the standard WHO algorithm. However, only one of the strains
detected by the standard WHO algorithm was detected by one of the molecular
methods. CONCLUSIONS: The molecular methods for enterovirus detection are more
sensitive than the virus isolation on cell culture lines, but in one case the
virus isolated on RD cell line was not detected by the molecular methods. The
results could be influenced by the small number of the samples investigated, by
the volume and the concentration method used for samples tested, and by the
limits of detection (LoD) of the enterovirus species in the samples, depending on
the method used.
PMID- 28704203
TI - Nurturing virtues of the medical profession: does it enhance medical students'
empathy?
AB - Objectives: To examine if the empathy levels of first-year medical students are
amenable to didactic interventions idealized to promote values inherent to
medical professional identity. Methods: This is a pretest-posttest study designed
to assess the empathy levels of first-year medical students (n=166) comprising
two consecutive classes of a Brazilian medical school, performed before and after
a didactic intervention. Students attended a course based on values and virtues
related to medical professional identity once a week over four months. Every
didactic approach (interviews with patients and physicians, supervised visits to
the hospital, and discussion of videotaped simulated consultations) was based on
"real-world" situations and designed to promote awareness of the process of
socialization. Students filled out the Jefferson Scale of Physician Empathy
(JSPE) on the first and last days of this course, and the pretest-posttest
analysis was performed using the Wilcoxon Signed Rank Test. Results: The mean
pretest JSPE score was 117.9 (minimum 92, maximum 135) and increased to 121.3
after the intervention (minimum 101, maximum 137). The difference was significant
(z=-5.2, p<.001.), with an effect size of 0.40. The observed increase was greater
among students with lower initial JSPE scores. Conclusions: Empathy is a
fundamental tool used to achieve a successful physician-patient relationship, and
it seems to permeate other virtues of a good physician. This study's results
suggest that medical students' empathy may be amenable to early curricular
interventions designed to promote a positive development of their professional
identity, even when empathy is not central in discussion.
PMID- 28704204
TI - Psychometric analysis of the Swedish version of the General Medical Council's
multi source feedback questionnaires.
AB - Objectives: To determine the internal consistency and the underlying components
of our translated and adapted Swedish version of the General Medical Council's
multisource feedback questionnaires (GMC questionnaires) for physicians and to
confirm which aspects of good medical practice the latent variable structure
reflected. Methods: From October 2015 to March 2016, residents in family medicine
in Sweden were invited to participate in the study and to use the Swedish version
to perform self-evaluations and acquire feedback from both their patients and
colleagues. The validation focused on internal consistency and construct
validity. Main outcome measures were Cronbach's alpha coefficients, Principal
Component Analysis, and Confirmatory Factor Analysis indices. Results: A total of
752 completed questionnaires from patients, colleagues, and residents were
analysed. Of these, 213 comprised resident self-evaluations, 336 were feedback
from residents' patients, and 203 were feedback from residents' colleagues.
Cronbach's alpha coefficients of the scores were 0.88 from patients, 0.93 from
colleagues, and 0.84 in the self-evaluations. The Confirmatory Factor Analysis
validated two models that fit the data reasonably well and reflected important
aspects of good medical practice. The first model had two latent factors for
patient-related items concerning empathy and consultation management, and the
second model had five latent factors for colleague-related items, including
knowledge and skills, attitude and approach, reflection and development,
teaching, and trust. Conclusions: The current Swedish version seems to be a
reliable and valid tool for formative assessment for resident physicians and
their supervisors. This needs to be verified in larger samples.
PMID- 28704205
TI - Multi-angle ZnO microstructures grown on Ag nanorods array for plasmon-enhanced
near-UV-blue light emitter.
AB - Metal enhanced ultraviolet light emission has been explored in ZnO/Ag hybrid
structures prepared by hydrothermal growth of multi-angled ZnO nanorods on
slanted Ag nanorods array fabricated by the thermal evaporation technique.
Slanted Ag nanorods are realized to be the stacking of non-spherical Ag
nanoparticles, resulting in asymmetric surface plasmon resonance spectra. The
surface roughness of Ag nanorod array films significantly influences the growth
mechanism of ZnO nanorods, leading to the formation of multi-angled ZnO
microflowers. ZnO/Ag hybrid structures facilitate the interfacial charge transfer
from Ag to ZnO with the realization of negative shift in binding energy of Ag 3d
orbitals by ~0.8 eV. These high quality ZnO nanorods in ZnO/Ag hybrid
nanostructures exhibit strong ultraviolet emission in the 383-396 nm region
without broad deep level emission, which can be explained by a suitable band
diagram. The metal enhanced photoluminescence is witnessed mainly due to
interfacial charge transfer with its dependence on surface roughness of bottom
layer Ag nanorods, number density of ZnO nanorods and diversity in the
interfacial area between Ag and ZnO nanorods. The existence of strong ultraviolet
light with minor blue light emission and appearance of CIE shade in strong violet
blue region by ZnO/Ag hybrid structures depict exciting possibilities towards
near UV-blue light emitting devices.
PMID- 28704206
TI - An autonomous robot inspired by insect neurophysiology pursues moving features in
natural environments.
AB - OBJECTIVE: Many computer vision and robotic applications require the
implementation of robust and efficient target-tracking algorithms on a moving
platform. However, deployment of a real-time system is challenging, even with the
computational power of modern hardware. Lightweight and low-powered flying
insects, such as dragonflies, track prey or conspecifics within cluttered natural
environments, illustrating an efficient biological solution to the target
tracking problem. APPROACH: We used our recent recordings from 'small target
motion detector' neurons in the dragonfly brain to inspire the development of a
closed-loop target detection and tracking algorithm. This model exploits
facilitation, a slow build-up of response to targets which move along long,
continuous trajectories, as seen in our electrophysiological data. To test
performance in real-world conditions, we implemented this model on a robotic
platform that uses active pursuit strategies based on insect behaviour. MAIN
RESULTS: Our robot performs robustly in closed-loop pursuit of targets, despite a
range of challenging conditions used in our experiments; low contrast targets,
heavily cluttered environments and the presence of distracters. We show that the
facilitation stage boosts responses to targets moving along continuous
trajectories, improving contrast sensitivity and detection of small moving
targets against textured backgrounds. Moreover, the temporal properties of
facilitation play a useful role in handling vibration of the robotic platform. We
also show that the adoption of feed-forward models which predict the sensory
consequences of self-movement can significantly improve target detection during
saccadic movements. SIGNIFICANCE: Our results provide insight into the neuronal
mechanisms that underlie biological target detection and selection (from a moving
platform), as well as highlight the effectiveness of our bio-inspired algorithm
in an artificial visual system.
PMID- 28704207
TI - The Adult Male Rape Victim: Forensic Description of a Series of 57 Cases.
AB - A retrospective analysis on 57 adult male victims of sexual violence has been
performed. Age, nationality and anamnesis of the victims, location of the
assault, type of violence, number and identity of the assailants, presence of
physical injuries, lapse of time between the assault and the request of medical
assistance, and toxicological and semen detection tests were analyzed. Victims
were mostly in the 31- to 40-year age group. Ten victims referred themselves as
either active homosexuals or bisexuals. Forced oral and/or anal penetration was
registered in 86.8% of cases, mostly performed by a single assailant. Anogenital
injuries were recorded in 61.4% of cases, whereas extragenital injuries in 35.1%:
abrasions and perianal reddening were the most frequent acute anogenital marks,
whereas the head and lower limbs were the body parts most commonly affected by
blunt trauma. No clinically severe injuries were found. Anal and perianal swabs
for semen detection tested positive in less than 20% cases, whereas oral swabs
always tested negative. When performed, nearly 50% of cases tested positive in
drug tests, above all for psychoactive substances. No definite forensic diagnosis
in terms of confirmation of rape was possible on the basis of type and topography
of injuries.
PMID- 28704208
TI - HGNET-BCOR Tumors of the Cerebellum: Clinicopathologic and Molecular
Characterization of 3 Cases.
AB - The central nervous system (CNS) high-grade neuroepithelial tumor with BCOR
alteration (CNS HGNET-BCOR) is a recently described molecular entity. We report 3
new CNS HGNET-BCOR cases sharing common clinical presentation and pathologic
features. The 3 cases concerned children aged 3 to 7 years who presented with a
voluminous mass of the cerebellum. Pathologic features included proliferation of
uniform spindle to ovoid cells with fine chromatin associated with a rich
arborizing capillary network. Methylation profiling classified these cases as CNS
HGNET-BCOR tumors. Polymerase chain reaction analysis confirmed the presence of
internal tandem duplications in the C-terminus of BCOR (BCOR-ITD), a
characteristic of these tumors, in all 3 cases. Immunohistochemistry showed a
strong nuclear BCOR expression. In 2 cases, local recurrence occurred within 6
months. The third case, a patient who received a craniospinal irradiation after
total surgical removal followed by a metronomics maintenance with irinotecan,
temozolomide, and itraconazole, is still free of disease 14 months after
diagnosis. In summary, CNS HGNET-BCOR represents a rare tumor occurring in young
patients with dismal prognosis. BCOR nuclear immunoreactivity is highly
suggestive of a BCOR-ITD. Whether CNS HGNET-BCOR should be classified among the
category of "embryonal tumors" or within the category of "mesenchymal,
nonmeningothelial tumors" remains to be clarified. Because CNS HGNET-BCOR share
pathologic features and characteristic BCOR-ITD with clear cell sarcoma of the
kidney, these tumors may represent local variants of the same entity.
PMID- 28704209
TI - Robotic Hand-Assisted Training for Spinal Cord Injury Driven by Myoelectric
Pattern Recognition: A Case Report.
AB - A 51-year-old man with an incomplete C6 spinal cord injury sustained 26 yrs ago
attended twenty 2-hr visits over 10 wks for robot-assisted hand training driven
by myoelectric pattern recognition. In each visit, his right hand was assisted to
perform motions by an exoskeleton robot, while the robot was triggered by his own
motion intentions. The hand robot was designed for this study, which can perform
six kinds of motions, including hand closing/opening; thumb, index finger, and
middle finger closing/opening; and middle, ring, and little fingers
closing/opening. After the training, his grip force increased from 13.5 to 19.6
kg, his pinch force remained the same (5.0 kg), his score of Box and Block test
increased from 32 to 39, and his score from the Graded Redefined Assessment of
Strength, Sensibility, and Prehension test Part 4.B increased from 22 to 24. He
accomplished the tasks in the Graded Redefined Assessment of Strength,
Sensibility, and Prehension test Part 4.B 28.8% faster on average. The results
demonstrate the feasibility and effectiveness of robot-assisted training driven
by myoelectric pattern recognition after spinal cord injury.
PMID- 28704210
TI - Factor XIII deficiency in south of Tunisia.
AB - : Factor XIII deficiency is a rare autosomal recessive disorder of hemostasis
characterized by a plasmatic factor XIII level less than 1% in homozygote and
bleeding as of the youth. The aim of the study is to describe the clinical
features and the outcome of the patients and to determine molecular
characteristics. A retrospective study, was conducted on seven patients with
factor XIII deficiency in the department of hematology and pediatrics, Hedi
Chaker Hospital, Sfax, Tunisia during the period of 14 years (2001-2014). The
activity of factor XIII in plasma of the patients was less than 1%. Seven
patients from five unrelated families were recorded (four men and three women).
Median age at diagnosis was 3.5 years. All patients had consanguineous parents.
Six patients presented umbilical bleeding and only three patients had
intracranial bleeding. Other bleeding features were seen, including skin and
mucosal bleeding, muscular hematoma, and splenic rupture. Recurrent abortions
were observed in one patient. The standard screening tests were normal. Genetic
analysis identified two mutations interesting the subunit A of factor XIII. All
patients received transfusion of fresh frozen plasma monthly. One patient was
died because of intracranial hemorrhage.Factor XIII deficiency is a rare bleeding
disorder which frequently increases in areas with high consanguinity. In our
study, we identified a founder mutation. The prognosis of the disorder is related
to hemorrhagic complications especially to life-threatening intracranial
bleeding. Prophylaxis consists of factor XIII concentrate or recombinant factor
XIII. If these are unavailable, fresh frozen plasma may be used.
PMID- 28704211
TI - How to emerge from the conservatism in clinical research methodology?
AB - PURPOSE OF REVIEW: Despite recent changes in clinical research methodology, many
challenges remain in drug development methodology. RECENT FINDINGS: Advances in
molecular biology and cancer treatments have changed the clinical research
landscape. Thus, we moved from empirical clinical oncology to molecular and
immunological therapeutic approaches. Along with this move, adapted dose-limiting
toxicities definitions, endpoints, and dose escalation methods have been
proposed. Moreover, the classical frontier between phase I, phase II, and phase
III has become unclear in particular for immunological approaches. So,
investigators are facing major challenges in drug development methodology.
SUMMARY: We propose to individualize clinical research using innovative
approaches to significantly improve patient outcomes and targeting what is
considered unmet need. Integrating high level of translational research and
performing well designed biomarker studies with great potential for clinical
practice are of utmost importance. This could be performed within new models of
clinical research networks and by building a strong collaboration between
academic, cooperative groups, on-site investigators, and pharma.
PMID- 28704212
TI - Endoscopic mucosal resection and endoscopic submucosal dissection: technique and
new directions.
AB - PURPOSE OF REVIEW: Most of small tumours in gastrointestinal tract are easily
removed by endoscopic mucosal resection (EMR). However, EMR are sometimes not
reliable to ensure the complete resection for large tumours. Although endoscopic
submucosal dissection (ESD) was developed, it had a higher risk for complications
such as perforation and bleeding. The techniques and clinical outcomes of EMR and
ESD are reviewed. RECENT FINDINGS: ESD is more effective for early gastric and
oesophageal cancer with higher en-bloc resection rate and lower local recurrence
in comparison to EMR. Several studies report favourable long-term outcomes of
ESD. ESD has become a standard technique in Japan and other East Asian countries.
Piecemeal resection using EMR technique is widely accepted for colorectal large
adenomas and results in good clinical outcomes in most patients. However,
apparent cancerous lesions need endoscopic en-bloc resection by ESD. SUMMARY:
Further development of the technique, devices and training systems will promote
worldwide standardization of ESD.
PMID- 28704213
TI - Menstrual pad, a cervical cancer screening tool, a population-based study in
rural India.
AB - In the rural areas of India, women generally use a piece of old cloth as a
menstrual device. The aim of this study was to detect human papilloma virus (HPV)
from menstrual blood on the menstrual pad and assess whether this could be a
useful screening tool for cervical cancer. In Jamkhed area of rural Maharashtra,
(population A), we collected menstrual pads from women who provided consent in
the 30-50 year age group. The women who had provided menstrual pads underwent HC2
testing. We standardized the method for extracting DNA by PCR from the menstrual
pad. The women who tested HPV positive, on the basis of HC2/PCR testing,
underwent colposcopy. In the rural population of Pune area of Maharashtra state
(population B), menstrual pads were collected. HPV was tested using the PCR
method. HPV-positive women and a few HPV-negative women, selected randomly,
underwent colposcopy and HC2 testing. In population A, 164 women provided their
used menstrual pads and also underwent an HC2 screening test. Of these, six
(3.2%) cases were reported as HPV positive. In population B, 365 women provided
their used menstrual pads for HPV testing, of which 18 (4.9%) cases were
diagnosed as HPV positive. The women who tested HPV positive, on the basis of PCR
testing, and 10% randomly selected HPV-negative cases (37) and 18 women who
voluntary requested testing underwent colposcopy and HC2 testing. The sensitivity
of menstrual pad HPV testing compared with gold standard HC2 testing was 83% [95%
confidence interval (CI): 0.47-0.97], 67% (95% CI: 0.30-0.91) and specificity was
99% (95% CI: 0.96-0.99), 88% (95% CI: 0.77-0.94) in population A and population
B, respectively. The sensitivity of diagnosing CIN lesion was 83% (95% CI: 0.44
0.97) and specificity was 95% (95% CI: 0.91-0.97). On the basis of the
sensitivity and specificity results, and the completely noninvasive, simple and
convenient method of detecting HPV, menstrual pad might be considered a cervical
cancer screening tool in rural Indian women.
PMID- 28704214
TI - Bile acids upregulate BRCA1 and downregulate estrogen receptor 1 gene expression
in ovarian cancer cells.
AB - Two major risk factors for ovarian cancer include loss-of-function mutations in
the BRCA1 (breast cancer 1, early onset) gene and aspects of estrogen metabolism.
Modulation of the levels of the normal BRCA1 allele and estrogen receptor
expression may therefore be a preventive strategy. Consensus binding motifs for
the bile acid-responsive transcription factor farnesoid X receptor were
identified in the BRCA1 and estrogen receptor 1 (ESR1) and estrogen receptor 2
(ESR2) genes, supported by chromatin immunoprecipitation sequencing data. Two
major bile acids, deoxycholic acid (DCA) and chenodeoxycholic acid (CDCA),
resulted in a greater than four-fold induction of BRCA1 transcript levels at 10
MUmol/l and a greater than six-fold induction at 50 MUmol/l relative to untreated
control OVCAR3 ovarian cancer cells. Conversely, CDCA and DCA at 10 MUmol/l
resulted in about a 75% decrease in ESR1 expression in response to 10 MUmol/l
CDCA and DCA and close to 90% reduction with 50 MUmol/l CDCA and DCA. Bile acids
had no effects on ESR2 gene transcript levels. The inverse regulation of BRCA1
and ESR1 gene expression in response to physiological levels of bile acids could
have important implications for disease penetrance and chemoprevention strategies
in carriers of BRCA1 mutations.
PMID- 28704215
TI - Inflammation and Oxidative Stress Limit Adaptation to Stretch-Shortening
Contractions in Aging.
PMID- 28704216
TI - Low-Back Pain Patients Learn to Adapt Motor Behavior With Adverse Secondary
Consequences.
AB - We hypothesize that changes in motor behavior in individuals with low-back pain
are adaptations aimed at minimizing the real or perceived risk of further pain.
Through reinforcement learning, pain and subsequent adaptations result in less
dynamic motor behavior, leading to increased loading and impoverished sensory
feedback, which contribute to cortical reorganization and proprioceptive
impairments that reduce the ability to control lumbar movement in a robust
manner.
PMID- 28704217
TI - Automatic Affective Evaluations of Physical Activity.
PMID- 28704218
TI - Priscilla M. Clarkson Undergraduate Travel Award.
PMID- 28704219
TI - Inflammaging and the Age-Specific Responsiveness to Stretch-Shortening
Contractions.
AB - With aging, muscle injury from rapid, continuous stretch-shortening contractions
(SSC) is prolonged, and maladaptation to moderate-velocity, intermittent SSC is
more common. We hypothesize that high baseline levels of inflammatory signaling
and oxidative stress may underlie these outcomes, whereas careful modulation of
high-intensity SSC training design resets basal conditions and permits muscle
adaptation to SSC.
PMID- 28704220
TI - Muscle Coordination and the Development of Musculoskeletal Disorders.
AB - The present article examines the hypothesis that each individual has unique
muscle coordination strategies (or signatures) that will have specific mechanical
effects on their musculoskeletal system. As such, some strategies would make some
people more at risk of developing musculoskeletal disorders than others.
Identification of individual coordination strategies might provide insight into
the development of musculoskeletal disorders.
PMID- 28704221
TI - Mechanisms Associated With Physical Activity Behavior: Insights From Rodent
Experiments.
AB - Dopaminergic signaling differences in the nucleus accumbens (NAcc) seemingly
predispose rats to adopt different physical activity behaviors. Physical activity
behavior also may be regulated through peripheral mechanisms (i.e., muscle and
fat derived as well as hormonal signals). We hypothesize that physical activity
behavior is regulated by the convergence of central and peripheral mechanisms
onto the NAcc.
PMID- 28704222
TI - Conceptualizing and Defining the Intention Construct for Future Physical Activity
Research.
AB - Intention has been an extremely important concept in physical activity theory and
research but is complicated by a double-barreled definition of a decision to
perform physical activity and the commitment to enact that decision. We put forth
the hypothesis that these separate meanings have different measurement
requirements, are situated in distinctly different intention-based models, and
show discrete findings when explaining physical activity motives.
PMID- 28704223
TI - Activities in a social networking-based discussion group by endoscopic retrograde
cholangiopancreatography doctors.
AB - BACKGROUND: Online social networking is increasingly being used among medical
practitioners. However, few studies have evaluated its use in therapeutic
endoscopy. Here, we aimed to analyze the shared topics and activities of a group
of endoscopic retrograde cholangiopancreatography (ERCP) doctors in a social
networking-based endoscopic retrograde cholangiopancreatography discussion group
(EDG). MATERIALS AND METHODS: Six ERCP trainers working in Xijing Hospital and 48
graduated endoscopists who had finished ERCP training in the same hospital were
invited to join in EDG. All group members were informed not to divulge any
private information of patients when using EDG. The activities of group members
on EDG were retrospectively extracted. The individual data of the graduated
endoscopists were collected by a questionnaire. RESULTS: From June 2014 to May
2015, 6924 messages were posted on EDG, half of which were ERCP related. In
total, 214 ERCP-related topics were shared, which could be categorized into three
types: sharing experience/cases (52.3%), asking questions (38.3%), and sharing
literatures/advances (9.3%). Among the 48 graduated endoscopists, 21 had a low
case volume of less than 50 per year and 27 had a high volume case volume of 50
or more. High-volume graduated endoscopists posted more ERCP-related messages
(P=0.008) and shared more discussion topics (P=0.003) compared with low-volume
graduated endoscopists. A survey showed that EDG was useful for graduated
endoscopists in ERCP performance and management of post-ERCP complications, etc.
CONCLUSION: A wide range of ERCP-related topics were shared on the social
networking-based EDG. The ERCP-related behaviors on EDG were more active in
graduated endoscopists with an ERCP case volume of more than 50 per year.
PMID- 28704224
TI - Inflammatory and multiple hepatocellular adenoma are associated with a higher
BMI.
AB - AIM: To identify patient and lesion characteristics associated with the
occurrence of single or multiple hepatocellular adenoma (HCA). PATIENTS AND
METHODS: Using a tertiary centre database, we retrospectively collected
information on patient and lesion characteristics, management and follow-up of
all patients with HCA included between 2001 and 2016. Patients were classified
into three groups; patients with a single HCA, 2-9 HCA and at least 10 HCA.
RESULTS: A total of 458 patients were diagnosed with HCA, including 121 (26.4%)
with single HCA, 235 (51.3%) with 2-9 HCA and 102 (22.3%) with at least 10 HCA.
Significant differences in the mean BMI were found, with the highest BMI in
patients with more than 10 HCA (P<0.05). The mean BMI was significantly higher in
patients with inflammatory HCA compared with steatotic HCA (31 vs. 26,
respectively, P<0.05). Steatotic HCA were more often single lesions (22/55, 40%),
whereas patients with inflammatory HCA were often diagnosed with multiple lesions
(122/166, 73%). CONCLUSION: Our series show a significantly higher BMI and
frequency of inflammatory HCA in patients with multiple HCA compared with single
HCA.
PMID- 28704225
TI - Intravenous Iron Sucrose for Treatment of Iron Deficiency Anemia in Pediatric
Inflammatory Bowel Disease.
AB - OBJECTIVES: Iron deficiency anemia (IDA) is a common complication of pediatric
inflammatory bowel disease (IBD), yet the effectiveness of oral iron
supplementation is limited. Intravenous iron sucrose is an effective and safe
alternative treatment for IDA in adults with IBD, but its role in the treatment
of IDA in pediatric IBD is unclear. The primary aim of this study was to evaluate
the use of iron sucrose in pediatric IBD subjects with IDA and determine the
clinical response as measured by improvement in hemoglobin concentration. The
secondary aim was to describe adverse events associated with iron sucrose use in
this cohort. METHODS: A retrospective chart review was performed of all pediatric
patients with IBD receiving iron sucrose infusions for IDA at a single tertiary
care center between 2011 and 2015. RESULTS: Seventy-two subjects (53 with Crohn
disease, 11 with ulcerative colitis, and 8 with IBD-unclassified) received a
total of 273 iron sucrose infusions. Forty-three subjects qualified for the
efficacy analysis. There was a significant increase in hemoglobin over the
treatment course, with mean (+/-SD) hemoglobin increasing from 9.6 +/- 1.2 g/dL
at baseline to 12.1 +/- 1.3 g/dL after iron sucrose treatment (P < 0.001).
Eighteen adverse events were reported in 13 subjects (18.1% of subjects and 6.6%
of infusions). No anaphylaxis reactions occurred and none of the adverse events
were, however, life-threatening or required hospitalization. CONCLUSIONS:
Intravenous iron sucrose is a safe and potentially efficacious treatment choice
for IDA in pediatric IBD.
PMID- 28704226
TI - Antibiotic resistance in Helicobacter pylori.
AB - PURPOSE OF REVIEW: Treatment of Helicobacter pylori is difficult nowadays because
of its high resistance. The prevalence and mechanism of resistance, the different
methods to detect it and the clinical implication of resistance were addressed in
several research papers last year. RECENT FINDINGS: Clarithromycin-resistant H.
pylori has been recognized by the WHO as 'high priority', for which new
antibiotics are needed. Moreover, the Maastricht consensus recommended, in areas
with high resistance, that susceptibility tests should be performed, at least
after a treatment failure. SUMMARY: Metronidazole and clarithromycin resistance
rates are alarming although they vary among populations. Tetracycline and
amoxicillin-resistance are very low in most countries. H. pylori resistance can
be detected by phenotypic or by molecular methods. Different break points may be
used when performing an antimicrobial susceptibility test, so comparing
resistance among different populations is challenging. Genomic techniques open
new possibilities in the diagnosis of H. pylori, and the detection of H. pylori
and its antimicrobial resistance in faeces is an interesting approach.
Eradication rates are dependent on the susceptibility of the strain to
metronidazole and clarithromycin, being lower in patients infected with a
resistant strain.
PMID- 28704227
TI - Mortality Among Hardmetal Production Workers: Occupational Exposures.
AB - OBJECTIVE: To generate quantitative exposure estimates for use in retrospective
occupational cohort mortality studies of the hardmetal industry. METHODS: Job
exposure matrices (JEMs) were constructed for cobalt, tungsten, and nickel over
the time period 1952 to 2014. The JEMs consisted of job class categories, based
on job titles and processes performed, and exposure estimates calculated from
available company industrial hygiene measurements. RESULTS: Exposure intervals of
one-half order magnitude were established for all three agents. Eight job classes
had significantly decreasing time trends for cobalt exposure; no significant time
trends were detected for tungsten or nickel exposures. CONCLUSIONS: The levels of
exposures determined for this study were similar to or lower than those
previously reported for the hardmetal industry during the 1952 to 2014 study
period.
PMID- 28704228
TI - Patient attitudes to clozapine initiation.
AB - Clozapine is widely underused. No study has assessed views of patients suitable
for, but not yet receiving, clozapine. We aimed to assess views of clozapine in
patients eligible for clozapine but not yet prescribed it by conducting
semistructured interviews with acutely unwell hospital in-patients. We
interviewed 61 of 116 eligible patients and 50 (82%) answered all questions. At
interview, 33 (54%) of 61 participants had heard of clozapine and 17 (30%) of 57
participants said they would take it if asked. Overall, 31 (57%) of 54
respondents said blood testing would not preclude them taking clozapine. The
necessity for hospital admission was seen as the greatest barrier to receiving
clozapine - 25 (49%) of 51 respondents stated this would be a reason for their
refusing clozapine. Concerns about adverse effects of clozapine were considered
sufficient to refuse clozapine in 23 (43.4%) of 53 respondents. Overall, 12 (24%)
of 50 respondents felt that clozapine would be helpful to them. Patients'
acceptance of clozapine is likely to be improved by offering the opportunity to
start clozapine at home and by improved education about the therapeutic benefits
of clozapine and the management of its adverse effects. Blood testing does not
appear to be an important barrier to the initiation of clozapine.
PMID- 28704229
TI - Treatment of Hyponatremic Encephalopathy in the Critically Ill.
AB - OBJECTIVES: Hyponatremic encephalopathy, symptomatic cerebral edema due to a low
osmolar state, is a medical emergency and often encountered in the ICU setting.
This article provides a critical appraisal and review of the literature on
identification of high-risk patients and the treatment of this life-threatening
disorder. DATA SOURCES, STUDY SELECTION, AND DATA EXTRACTION: Online search of
the PubMed database and manual review of articles involving risk factors for
hyponatremic encephalopathy and treatment of hyponatremic encephalopathy in
critical illness. DATA SYNTHESIS: Hyponatremic encephalopathy is a frequently
encountered problem in the ICU. Prompt recognition of hyponatremic encephalopathy
and early treatment with hypertonic saline are critical for successful outcomes.
Manifestations are varied, depending on the extent of CNS's adaptation to the
hypoosmolar state. The absolute change in serum sodium alone is a poor predictor
of clinical symptoms. However, certain patient specific risks factors are
predictive of a poor outcome and are important to identify. Gender (premenopausal
and postmenopausal females), age (prepubertal children), and the presence of
hypoxia are the three main clinical risk factors and are more predictive of poor
outcomes than the rate of development of hyponatremia or the absolute decrease in
the serum sodium. CONCLUSIONS: In patients with hyponatremic encephalopathy
exhibiting neurologic manifestations, a bolus of 100 mL of 3% saline, given over
10 minutes, should be promptly administered. The goal of this initial bolus is to
quickly treat cerebral edema. If signs persist, the bolus should be repeated in
order to achieve clinical remission. However, the total change in serum sodium
should not exceed 5 mEq/L in the initial 1-2 hours and 15-20 mEq/L in the first
48 hours of treatment. It has recently been demonstrated in a prospective fashion
that 500 mL of 3% saline at an infusion rate of 100 mL per hour can be given
safely. It is critical to recognize the early signs of cerebral edema (nausea,
vomiting, and headache) and intervene with IV 3% sodium chloride as this is the
time to intervene rather than waiting until more severe symptoms develop.
Cerebral demyelination is a rare complication of overly rapid correction of
hyponatremia. The principal risk factors for cerebral demyelination are
correction of the serum sodium more than 25 mEq/L in the first 48 hours of
therapy, correction past the point of 140 mEq/L, chronic liver disease, and
hypoxic/anoxic episode.
PMID- 28704230
TI - Effect of Esophageal Cancer Surgeon Volume on Management and Mortality From
Emergency Upper Gastrointestinal Conditions: Population-based Cohort Study.
AB - OBJECTIVE: To study the influence of esophageal cancer surgeon volume upon
mortality from upper gastrointestinal emergencies. BACKGROUND: Volume-outcome
relationships led to the centralization of esophageal cancer surgery. METHODS:
Hospital Episode Statistics data were used to identify patients admitted to
hospitals within England (1997-2012). The influence of esophageal high-volume
(HV) cancer surgeon status (>=5 resections per year) upon 30-day and 90-day
mortality from esophageal perforation (EP), paraesophageal hernia causing
obstruction or gangrene (PEH) and perforated peptic ulcer (PPU) was analyzed,
independent of HV esophageal cancer center status and patient and disease
specific confounding factors. RESULTS: A total of 3707, 12,411, and 57,164
patients with EP, PEH, and PPU, respectively, were included. The observed 90-day
mortality was 36.5%, 11.5%, and 29.0% for EP, PEH, and PPU,
respectively.Management by HV cancer surgeon was independently associated with
significant reductions in 30-day and 90-day mortality from EP (odds ratio, OR
0.51, 95% confidence interval, CI, 0.40-0.66), PEH (OR=0.70, 95% CI 0.53-0.91),
and PPU (OR=0.85, 95% CI 0.7-0.95). Subset analysis of those patients receiving
primary surgery as treatment showed no change in mortality when performed by HV
cancer surgeons.However HV cancer surgeons performed surgery as primary treatment
more commonly for EP (OR=2.38, 95% CI 1.87-3.04) and PEH (OR=2.12, 95% CI 1.79
2.51). Furthermore surgery was independently associated with reduced mortality
for all 3 conditions. CONCLUSION: The complex elective workload of HV esophageal
cancer surgeons appears to lower the threshold for surgical intervention in
specific upper gastrointestinal emergencies such as EP and PEH, which in turn
reduces mortality.
PMID- 28704231
TI - Male Fertility After Inguinal Hernia Mesh Repair: A National Register Study.
AB - OBJECTIVE: To determine whether patients who receive an inguinal hernia repair
father the same number of children as the background population. BACKGROUND:
Although the effect of inguinal hernia repair on male fertility has previously
been investigated through indirect measures, no previous studies have evaluated
the final measure of male fertility, which is the number of children fathered by
patients. METHODS: Prospectively collected data on 32,621 male patients between
the ages of 18 and 55 years who received 1 or more inguinal hernia repairs during
the years 1998 to 2012 were found in 5 comprehensive Danish linked registers.
Patients were matched with 97,805 controls, and the number of fathered children
was recorded as the primary outcome. RESULTS: Patients who were operated
unilaterally fathered more children than controls (156 vs 147 children per 1000
individuals, P = 0.02), whereas patients who were operated bilaterally fathered
the same number of children as controls. Unilateral Lichtenstein operation
resulted in an increase in number of children fathered by patients (161 vs 151
children per 1000 patients, P = 0.009). No difference in the number of children
fathered was found for any year following operation. Meanwhile, time between
operation and first child was longer among controls than patients (log-rank P =
0.003). The youngest (18-30 years of age) bilaterally operated patients fathered
the same number of children as controls. CONCLUSIONS: Patients who underwent
inguinal hernia repair using Lichtenstein technique or laparoscopic approach did
not father fewer children than expected. Thus, inguinal hernia repair using
Lichtenstein or laparoscopic approach did not impair male fertility.
PMID- 28704232
TI - Laparoscopic Transcystic Stenting and Postoperative ERCP for the Management of
Common Bile Duct Stones at Laparoscopic Cholecystectomy.
PMID- 28704233
TI - Ultrasound Diagnosis of Spontaneous Nephrocutaneous Fistula.
PMID- 28704234
TI - CE: Tuberculosis: A New Screening Recommendation and an Expanded Approach to
Elimination in the United States.
AB - : Nurses play a critical role in the diagnosis and treatment of tuberculosis and
in the prevention of tuberculosis transmission through infection control
practices. To eliminate tuberculosis in the United States, however, an expanded
approach to testing and treating people with latent tuberculosis infection must
be implemented. Recently, the U.S. Preventive Services Task Force (USPSTF) issued
a new recommendation statement on latent tuberculosis infection testing that
expands nurses' opportunities to identify at-risk populations for tuberculosis
prevention. In combination with newer testing methodologies and shorter treatment
regimens, implementation of the USPSTF recommendation has the potential to remove
previously existing barriers to screening and treatment of both patients and
health care providers. This article provides a general overview of tuberculosis
transmission, pathogenesis, and epidemiology; presents preventive care
recommendations for targeted testing among high-risk groups; and discusses the
USPSTF recommendation's applicability to public health and primary care practice
in the United States.
PMID- 28704235
TI - CE: Beyond Maternity Nursing: The Baby-Friendly Hospital Initiative.
AB - : The Baby-Friendly Hospital Initiative (BFHI) is a program developed by the
World Health Organization (WHO) and the United Nations Children's Fund (UNICEF)
to promote breastfeeding in hospitals and birthing facilities worldwide. Since
the program was launched in 1991, breastfeeding initiation, duration, and
exclusivity have increased globally, a trend largely attributed to changes in
hospital policies and practices brought about by the BFHI. This article provides
an overview of these practices and policies, the institutional benefits of
achieving BFHI certification, and the process through which health care
facilities can do so. All nurses-whether they work in maternity care or another
nursing specialty in a hospital, ambulatory, or community setting-can play a role
in promoting societal health through their support of long-term breastfeeding as
recommended by the WHO and UNICEF.
PMID- 28704236
TI - Liver X receptors agonist T0901317 downregulates matrix metalloproteinase-9
expression in non-small-cell lung cancer by repressing nuclear factor-kappaB.
AB - The liver X receptors (LXRs) is an important component of the nuclear receptor
(NR) superfamily. Previous studies have shown that the LXRs possessed antitumor
activity in various types of tumor cells. However, the complicated mechanisms
underlying the antitumor activity remain largely unexplored. In this study, we
incubated A549 cells with the compound T0901317, a specific LXRs agonist, for 24
h. The MTT assay was used to assess cell viability. Transwell assays were used to
evaluate cell migration and invasion. The shRNA was utilized for RNA
interference. The target gene and protein expression levels were assessed using
reverse transcription-PCR and western blot assay. The DNA-binding activity of
nuclear factor kappaB (NF-kappaB) was examined using electrophoretic mobility
shift assays. Luciferase reporter assay was used to detect the binding of NF
kappaB to the matrix metalloproteinase-9 (MMP-9) promoter. We found that T0901317
inhibited the invasion and migration of A549 cells in a dose-dependent manner.
Meanwhile, we further indicated that activation of LXRbeta, one subtype of LXRs,
can downregulate MMP-9 expression. More importantly, activation of LXRbeta
triggered by T0901317 inhibited the invasion and metastasis of A549 cells by
repressing NF-kappaB/MMP-9 signaling pathway. Taken together, our study shows
that activation of LXRs triggered by T0901317 inhibits the invasion and
metastasis of human non-small-cell lung cancer by repressing the NF-kappaB/MMP-9
signaling pathway.
PMID- 28704237
TI - Geraniin inhibits migration and invasion of human osteosarcoma cancer cells
through regulation of PI3K/Akt and ERK1/2 signaling pathways.
AB - Geraniin, an active compound isolated from Geranium sibiricum, was found to
inhibit proliferation and induce apoptosis of tumor cells. However, the
antimetastatic effects of geraniin remain elusive. Our study found the potential
antitumor mechanisms of geraniin through inhibiting the migration and invasion of
human osteosarcoma U2OS cells. The western blot, gelatin zymography, and reversed
transcription-PCR analysis showed that geraniin suppressed matrix
metalloproteinase-9 (MMP-9) expression in a concentration-dependent manner.
Geraniin potently suppressed the phosphorylation of extracellular signal
regulating kinase (ERK)1/2, phosphatidylinositide-3-kinase (PI3K), and Akt, but
did not affect phosphorylation of p38 mitogen-activated protein kinase and c-Jun
N-terminal kinase. Furthermore, when transforming growth factor-beta1 (TGF-beta1)
was used as an agonist, geraniin inhibited TGF-beta1-mediated cell invasion and
upregulation of MMP-9. These results suggested that geraniin inhibited U2OS cell
migration and invasion by reducing the expression of MMP-9 through the PI3K/Akt
and ERK1/2 signaling pathways.
PMID- 28704239
TI - Dexmedetomidine and Post-Electroconvulsive Therapy Agitation Scores.
PMID- 28704238
TI - Perspectives about mental health, illness, and recovery.
AB - PURPOSE OF REVIEW: Patient and physician perspectives about mental health,
illness, and recovery, which affect different aspects of help seeking and
healthcare, needs to be understood and theorized. RECENT FINDINGS: People seem to
simultaneously hold multiple and contradictory illness beliefs and seek help from
diverse sources of cure and healing. Explanatory models elicited at baseline do
not predict outcomes of illness, change over time, and are dependent on the
interaction between the trajectory of individual's illness and the sociocultural
milieu. Illness narratives contextualize the patient, describe the patient's
reality and his/her ways of coping, and attempt to make sense of illness
experiences, control them, and improve quality of life. On the other hand,
diversity of beliefs among psychiatrists, family physicians, and public health
specialists is dependent on their disciplinary perspectives. Nevertheless, the
variability within psychiatric syndromes and the inability to predict individual
trajectories of illness support cultural beliefs about uncertainties of life.
These are identified by cultures through idioms and metaphors and labeled as
luck, chance, karma, fate, punishment by God, evil spirits, black magic, disease
and so on. SUMMARY: There is a need for a broad-based approach to mental health,
which allows individuals to make sense of their contexts and find meaning in
life.
PMID- 28704240
TI - Computed tomography angiography defined vulnerable plaque in a patient with low
high-density lipoprotein cholesterol and subsequent myocardial infarction.
PMID- 28704241
TI - Prognostic value of electrocardiogram exercise testing for risk stratification in
asymptomatic coronary artery disease.
AB - BACKGROUND: Several variables of electrocardiogram exercise testing (EET) predict
cardiovascular events in the general population and in patients with coronary
artery disease (CAD). However, most of the studies have not included patients
with asymptomatic CAD. The aim of this study was to evaluate the prognostic value
of EET in asymptomatic CAD patients. PATIENTS AND METHODS: We carried out a
retrospective single-center analysis including all patients with asymptomatic CAD
documented by angiography who underwent EET from January 2010 to December 2013. A
number of EET variables and three exercise scores [Duke Treadmill Score (DTS),
Morise score, and FIT score] were analyzed. The primary endpoint was the combined
incidence of myocardial infarction (MI), myocardial revascularization, and death
from any cause during follow-up. RESULTS: A total of 306 patients were included
(mean age was 65+/-10 years, 61% had previous MI, and the median exercise
capacity was 9.4+/-2.7 metabolic equivalent of task). The primary endpoint
occurred in 15.7% of patients during 3.3 years of follow-up. The DTS and FIT were
independent predictors of the primary endpoint unlike the Morise score (DTS:
hazard ratio=0.91, 95% confidence interval: 0.85-0.99, P=0.018; FIT score: 0.99,
0.98-0.996, P=0.001; Morise score: 0.97, 0.93-1.02, P=0.20). The DTS was
independent predictor of MI or revascularization, whereas FIT predicted death
from any cause. Excluding patients with early revascularization, DTS had no
predictive power at the composite endpoint. CONCLUSION: In our population with
asymptomatic CAD, FIT and DTS had significant value for risk prediction and
consequently the EET can be a valid tool in the clinical follow-up of this
population.
PMID- 28704242
TI - Long-term clinical outcome after implantation of the self-expandable STENTYS
stent in a large, multicenter cohort.
AB - OBJECTIVE: The objective of the study was to retrospectively evaluate the long
term clinical outcome after implantation of the self-expandable (SE) STENTYS
stent in a large multicenter cohort. BACKGROUND: Incomplete stent apposition is
known to cause higher rates of myocardial infarction (MI) and stent thrombosis.
Because of its self-expanding features, the SE STENTYS stent adapts to the vessel
wall and is therefore expected to minimize malapposition and therefore the rates
of MI and stent thrombosis. PATIENTS AND METHODS: Treatment with a total of 351
SE coronary stents was attempted in 314 patients of a cohort from three German
institutions between 2011 and 2015. Technical success was achieved with 331/351
(94%) stents. Patients treated successfully with SE stents (n=298) were followed
up using the primary outcome measure of target lesion failure (TLF), a combined
endpoint of cardiac mortality, recurrent target vessel MI, acute stent
thrombosis, and clinically driven target lesion revascularization. Follow-up was
complete in 268/298 (90%) patients with a median follow-up period of 2.5
(interquartile range: 1.4-3.3) years. RESULTS: TLF occurred in 54/298 (18%)
patients. Event rates were 7.5% for cardiac mortality, 11.6% for target vessel
MI, and 5.2% for clinically driven target lesion revascularization. Acute stent
thrombosis occurred in 2/298 (0.7%). Overall, stent thrombosis had an incidence
of 2.6% within the follow-up period. ST-elevation MI at baseline (P=0.02) and a
dual antiplatelet therapy with clopidogrel for only 6 months (P=0.04) were the
only clinical factors linked to the absence of TLF. CONCLUSION: Technical success
of SE coronary stent implantation in an all-comer cohort of patients was high,
although the rate of TLF and stent thrombosis during long-term follow-up was also
relatively high.
PMID- 28704243
TI - Dynamic neointimal pattern after drug-eluting stent implantation defined by
optical coherence tomography.
AB - OBJECTIVES: Certain neointimal patterns including neoatherosclerosis (NA) are
known to be associated with poor clinical outcome. The prevalence and time course
of different neointimal patterns have not been studied systematically. The aim of
this study was to investigate the serial changes in neointimal pattern after drug
eluting stent implantation. PATIENTS AND METHODS: A total of 132 patients with
207 drug-eluting stents, who underwent two follow-up optical coherence tomography
studies at 6 and 12 months, were included. Neointimal patterns were categorized
as homogeneous, heterogeneous, layered, or NA using optical coherence tomography.
Quantitative and qualitative analyses of neointima were carried out. RESULTS:
Both at 6 and at 12 months, the homogenous neointima was the predominant type
(>75%), followed by the layered and the heterogeneous pattern. At 12 months,
progression to NA was observed in 0.6% of the patients in the homogeneous group,
in 5.6% of the patients in the heterogeneous group, and in 3.9% of the patients
in the layered group. Regression to the homogeneous pattern was observed in 5.6%
of the patients in the heterogeneous group and 11.5% of the patients in the
layered group. CONCLUSION: The homogenous neointima is the predominant pattern
both at 6 and at 12 months. The neointimal pattern changed between 6 and 12
months in 10.6% of stents. Further studies are needed to understand the
mechanisms of these neointimal changes and their clinical significance.
PMID- 28704244
TI - Implementation of a Standardized Transfusion Protocol for Cardiac Patients
Treated With Venoarterial Extracorporeal Membrane Oxygenation Is Associated With
Decreased Blood Component Utilization and May Improve Clinical Outcome.
AB - BACKGROUND: Extracorporeal membrane oxygenation supplies oxygenated blood to the
body supporting the heart and lungs. Survival rates of 20% to 50% are reported
among patients receiving ECMO for cardiac arrest, severe cardiogenic shock, or
failure to wean from cardiopulmonary bypass following cardiac surgery. Bleeding
is one of the most common complications in ECMO patients due to coagulopathy,
systemic anticoagulation, and the presence of large bore cannulas at systemic
pressure. Absence of a standardized transfusion protocol in this population leads
to inconsistent transfusion practices. Here, we assess a newly developed
dedicated transfusion protocol in this clinical setting. METHODS: Data were
retrospectively reviewed for the first 30 consecutive cardiac ECMO patients prior
and post implementation of the ECMO transfusion protocol. Diagnoses, laboratory
results, blood component utilization, and outcomes were collected and analyzed.
RESULTS: Comorbidities were similar between the 2 eras, as well as the pre-ECMO
ejection fraction (P = .568) and duration on ECMO (P = .278). Transfusion
utilization data revealed statistically significant decreases in almost all blood
components and a savings in blood component acquisition costs of 51% ($175, 970).
In addition, an almost 2-fold increase in survival rate was observed in the post
ECMO transfusion protocol era (63% vs 33%; relative risk = 1.82; 95% confidence
interval, 1.07-3.10; P = .028). CONCLUSIONS: Our data indicate that
implementation of a standardized transfusion protocol, using more restrictive
transfusion indications in cardiac ECMO patients, was associated with reduced
blood product utilization, decreased complications, and improved survival. This
multidepartmental approach facilitates better communication and adherence to
consensus clinical decision making between intensive care unit, surgery, and
transfusion service and optimizes care of complicated and acutely ill patients.
PMID- 28704245
TI - Inciting Events Associated With Lumbar Facet Joint Pain.
AB - BACKGROUND: Low back pain is the leading cause of years lost to disability with
approximately 15%-25% of the chronic back pain population suffering from lumbar
facet arthropathy. No large-scale study has sought to systematically identify
inciting events for lumbar facet arthropathy. The aim of this study is to
quantify the proportion of individuals with lumbar facetogenic pain who report a
specific precipitating event(s) and to determine if there is a correlation
between these events and treatment outcome. METHODS: Institutional electronic
medical records were searched based on the current procedural terminology (CPT)
codes representing lumbar facet joint radiofrequency ablation for procedures
performed between January 2007 and December 2015. All patients had obtained >=50%
pain relief based on 6-hour pain diaries after 1 or more diagnostic facet blocks.
A positive outcome was defined as >=50% pain relief sustained for longer than 3
month after procedure, without additional procedural interventions. RESULTS: One
thousand sixty-nine people were included in analysis. In the 52% of individuals
who described an inciting event, the most commonly reported causes were falls
(11%), motor vehicle collisions (11%), sports-related injuries (11%, of which
weightlifting accounted for 62%), nonspine postsurgical injuries (2%), and
"other" (17%). Six hundred seventeen (57.7%) individuals experienced >=50% pain
relief sustained for >3 months. Patients whose pain was preceded by an inciting
event were more likely to have a positive outcome than those who could not recall
a specific precipitating factor (odds ratio, 1.5; confidence interval, 1.02-2.1,
P = .01). Another factor associated with outcome was shorter duration of pain
(8.1 +/- 9.2 vs 9.7 +/- 10.1 years, P = .02), with an observed modifier effect of
age on outcomes. For a 1-year increase in age, there was a 10% increase in the
odds of a positive response. CONCLUSIONS: Inciting events are common in patients
diagnosed with lumbar facetogenic pain and may be associated with a positive
outcome.
PMID- 28704246
TI - The Effect of Glycopyrrolate on the Incidence of Hypotension and Vasopressor
Requirement During Spinal Anesthesia for Cesarean Delivery: A Meta-analysis.
AB - BACKGROUND: The objective of this meta-analysis was to determine the efficacy of
glycopyrrolate at reducing spinal hypotension during cesarean delivery. METHODS:
A literature search was performed to identify randomized controlled trials
investigating the effect of glycopyrrolate on spinal-induced hypotension during
cesarean delivery. Primary outcomes were intraoperative hypotension and
vasopressor requirement (phenylephrine equivalents). Secondary outcomes included
heart rate (HR), nausea and vomiting, dry mouth, and Apgar scores. Risk ratios
(RRs), and mean differences (MDs) were calculated using random-effects modeling
with 95% confidence intervals for primary outcomes and 99% confidence intervals
for secondary outcomes. RESULTS: Five randomized controlled trials met our
inclusion criteria. A total of 311 patients were included: 153 received
glycopyrrolate and 158 placebo. The incidence of spinal-induced hypotension was
no different with prophylactic glycopyrrolate compared to control (RR, 0.93 [0.71
1.21]; P = .59), but the total phenylephrine dose required was significantly
reduced with glycopyrrolate (MD, -62.64 MUg [-107.61 to -17.66 MUg]; P = .006).
The maximal HR achieved in the glycopyrrolate group was significantly higher
compared to controls (MD, 15.85 bpm [5.40-26.31]; P < .0001); however, the
incidence of bradycardia was not statistically different. The incidence of
intraoperative nausea and vomiting was not different between groups; however,
glycopyrrolate increased the risk of dry mouth (RR, 5.15 [1.82-14.57]; P <
.0001). Apgar scores at 1 and 5 minutes did not differ between groups.
CONCLUSIONS: Prophylactic glycopyrrolate does not reduce the incidence of spinal
induced hypotension but results in a modest reduction in vasopressor requirements
while increasing maternal HR.
PMID- 28704247
TI - Comparison of Registered and Reported Outcomes in Randomized Clinical Trials
Published in Anesthesiology Journals.
AB - BACKGROUND: Randomized clinical trials (RCTs) provide high-quality evidence for
clinical decision-making. Trial registration is one of the many tools used to
improve the reporting of RCTs by reducing publication bias and selective outcome
reporting bias. The purpose of our study is to examine whether RCTs published in
the top 6 general anesthesiology journals were adequately registered and whether
the reported primary and secondary outcomes corresponded to the originally
registered outcomes. METHODS: Following a prespecified protocol, an electronic
database was used to systematically screen and extract data from RCTs published
in the top 6 general anesthesiology journals by impact factor (Anaesthesia,
Anesthesia & Analgesia, Anesthesiology, British Journal of Anaesthesia, Canadian
Journal of Anesthesia, and European Journal of Anaesthesiology) during the years
2007, 2010, 2013, and 2015. A manual search of each journal's Table of Contents
was performed (in duplicate) to identify eligible RCTs. An adequately registered
trial was defined as being registered in a publicly available trials registry
before the first patient being enrolled with an unambiguously defined primary
outcome. For adequately registered trials, the outcomes registered in the trial
registry were compared with the outcomes reported in the article, with outcome
discrepancies documented and analyzed by the type of discrepancy. RESULTS: During
the 4 years studied, there were 860 RCTs identified, with 102 RCTs determined to
be adequately registered (12%). The proportion of adequately registered trials
increased over time, with 38% of RCTs being adequately registered in 2015. The
most common reason in 2015 for inadequate registration was registering the RCT
after the first patient had already been enrolled. Among adequately registered
trials, 92% had at least 1 primary or secondary outcome discrepancy. In 2015, 42%
of RCTs had at least 1 primary outcome discrepancy, while 90% of RCTs had at
least 1 secondary outcome discrepancy. CONCLUSIONS: Despite trial registration
being an accepted best practice, RCTs published in anesthesiology journals have a
high rate of inadequate registration. While mandating trial registration has
increased the proportion of adequately registered trials over time, there is
still an unacceptably high proportion of inadequately registered RCTs. Among
adequately registered trials, there are high rates of discrepancies between
registered and reported outcomes, suggesting a need to compare a published RCT
with its trial registry entry to be able to fully assess the quality of the
study. If clinicians base their decisions on evidence distorted by primary
outcome switching, patient care could be negatively affected.
PMID- 28704248
TI - Low End-Tidal Carbon Dioxide at the Onset of Emergent Trauma Surgery Is
Associated With Nonsurvival: A Case Series.
AB - BACKGROUND: End-tidal carbon dioxide (EtCO2) is a valuable marker of the return
of adequate circulation after cardiac arrest due to medical causes. Previously,
the prognostic value of capnography in trauma has been studied among limited
populations in prehospital and emergency department settings. We aimed to
investigate the relationship between early intraoperative EtCO2 and nonsurvival
of patients undergoing emergency surgery at a level 1 academic trauma center as a
case series. If there is a threshold below which survival was extremely unlikely,
it might be useful in guiding decision-making in the early termination of futile
resuscitative efforts. METHODS: After institutional review board approval, a data
set was created to investigate the relationship between EtCO2 values at the onset
of emergent trauma surgery and nonsurvival. Patients who were admitted and
transferred to the operating room (OR) directly from a resuscitation bay were
identified using the Ryder Center trauma registry (October 1, 2013, to June 30,
2016). Electronic records from the hospital's anesthesia information management
system were queried to identify the matching anesthesia records. The maximum
EtCO2 values within 5 and 10 minutes of the onset of mechanical ventilation in
the OR were determined for patients undergoing general anesthesia with mechanical
ventilation. Patients were divided into 2 groups: those who were discharged from
the hospital alive (survivors) and those who died in the hospital before
discharge (nonsurvivors). The threshold EtCO2 giving a positive predictive value
of 100% for in-hospital mortality was determined from a graphical analysis of the
data. Association of determined threshold and mortality was analyzed using the 2
tailed Fisher exact test. RESULTS: There were 1135 patients who met the inclusion
criteria. Within the first 5 minutes of the onset of mechanical ventilation in
the OR, if the maximum EtCO2 value was <=20 mm Hg, hospital mortality was 100%
(21/21, 95% binomial confidence interval, 83.2%-100%). CONCLUSIONS: A maximum
EtCO2 <=20 mm Hg within 5 minutes of the onset of mechanical ventilation in the
OR may be useful in decision-making related to the termination of resuscitative
efforts during emergent trauma surgery. However, a large-scale study is needed to
establish the statistical reliability of this finding before potential adoption.
PMID- 28704249
TI - Patient Survey of Referral From One Surgeon to Another to Reduce Maximum Waiting
Time for Elective Surgery and Hours of Overutilized Operating Room Time.
AB - BACKGROUND: Studies of shared (patient-provider) decision making for elective
surgical care have examined both the decision whether to have surgery and
patients' understanding of treatment options. We consider shared decision making
applied to case scheduling, since implementation would reduce labor costs.
METHODS: Study questions were presented in sequence of waiting times, starting
with 4 workdays. "Assume the consultant surgeon (ie, the surgeon in charge) you
met in clinic did not have time available to do your surgery within the next 4
workdays, but his/her colleague would have had time to do your surgery within the
next 4 workdays. Would you have wanted to discuss with a member of the surgical
team (eg, the scheduler or the surgeon) the availability of surgery with a
different, equally qualified surgeon at Mayo Clinic who had time available within
the next 4 workdays, on a date of your choosing?" There were 980 invited patients
who underwent lung resection or cholecystectomy between 2011 and 2016; 135
respondents completed the study and 6 respondents dropped out after the study
questions were displayed. RESULTS: The percentages of patients whose response to
the study questions was "4 days" were 58.8% (40/68) among lung resection patients
and 58.2% (39/67) among cholecystectomy patients. The 97.5% 2-sided confidence
interval for the median maximum wait was 4 days to 4 days. Patients' choices for
the waiting time sufficient to discuss having another surgeon perform the
procedure did not differ between procedures (P = .91). Results were insensitive
to patients' sex, age, travel time to hospital, or number of office visits before
surgery (all P >= .20). CONCLUSIONS: Our results indicate that bringing up the
option with the patient of changing surgeons when a colleague is available and
has the operating room time to perform the procedure sooner is being respectful
of most patients' individual preferences (ie, patient-centered).
PMID- 28704250
TI - Abnormal Calcium Levels During Trauma Resuscitation Are Associated With Increased
Mortality, Increased Blood Product Use, and Greater Hospital Resource
Consumption: A Pilot Investigation.
AB - BACKGROUND: Admission hypocalcemia predicts both massive transfusion and
mortality in severely injured patients. However, the effect of calcium
derangements during resuscitation remains unexplored. We hypothesize that any
hypocalcemia or hypercalcemia (either primary or from overcorrection) in the
first 24 hours after severe injury is associated with increased mortality.
METHODS: All patients at our institution with massive transfusion protocol
activation from January 2013 through December 2014 were identified. Patients
transferred from another hospital, those not transfused, those with no ionized
calcium (Ca) measured, and those who expired in the trauma bay were excluded.
Hypocalcemia and hypercalcemia were defined as any level outside the normal range
of Ca at our institution (1-1.25 mmol/L). Receiver operator curve analysis was
also used to further examine significant thresholds for both hypocalcemia and
hypercalcemia. Hospital mortality was compared between groups. Secondary outcomes
included advanced cardiovascular life support, damage control surgery, ventilator
days, and intensive care unit days. RESULTS: The massive transfusion protocol was
activated for 77 patients of whom 36 were excluded leaving 41 for analysis.
Hypocalcemia occurred in 35 (85%) patients and hypercalcemia occurred in 9 (22%).
Mortality was no different in hypocalcemia versus no hypocalcemia (29% vs 0%; P =
.13) but was greater in hypercalcemia versus no hypercalcemia (78% vs 9%; P <
.01). Receiver operator curve analysis identified inflection points in mortality
outside a Ca range of 0.84 to 1.30 mmol/L. Using these extreme values, 15 (37%)
had hypocalcemia with a 60% mortality (vs 4%; P < .01) and 9 (22%) had
hypercalcemia with a 78% mortality (vs 9%; P < .01). Patients with extreme
hypocalcemia and hypercalcemia also received more red blood cells, plasma,
platelets, and calcium repletion. CONCLUSIONS: Hypocalcemia and hypercalcemia
occur commonly during the initial resuscitation of severely injured patients.
Mild hypocalcemia may be tolerable, but more extreme hypocalcemia and any
hypercalcemia should be avoided. Further assessment to define best practice for
calcium management during resuscitation is warranted.
PMID- 28704252
TI - Bumetanide Treatment for Psychiatric Disorders and the Modulation of Central
Nitric Oxide Metabolism.
PMID- 28704253
TI - Preeclampsia in a factor XI deficient woman: discussion about one case.
PMID- 28704254
TI - EFFICACY AND SAFETY OF RANIBIZUMAB FOR THE TREATMENT OF CHOROIDAL
NEOVASCULARIZATION DUE TO UNCOMMON CAUSE: Twelve-Month Results of the MINERVA
Study.
AB - PURPOSE: To evaluate the efficacy and safety of ranibizumab 0.5 mg in adult
patients with choroidal neovascularization because of an uncommon cause enrolled
in the 12-month MINERVA study. METHODS: In this Phase III, double-masked study,
adult (>=18 years) patients (N = 178) were randomized 2:1 to receive either
ranibizumab (n = 119) or sham (n = 59) at baseline and, if needed, at Month 1 and
open-label individualized ranibizumab from Month 2. Best-corrected visual acuity
change from baseline to Month 2 (primary endpoint) and Month 12, treatment
exposure, and safety over 12 months were reported. Subgroup analysis was
conducted on five predefined choroidal neovascularization etiologies (angioid
streak, postinflammatory, central serous chorioretinopathy, idiopathic, and
miscellaneous). RESULTS: Ranibizumab showed superior efficacy versus sham from
baseline to Month 2 (adjusted least-squares mean best-corrected visual acuity:
+9.5 vs. -0.4 letters; P < 0.001). At Month 12, the mean best-corrected visual
acuity change was +11.0 letters (ranibizumab) and +9.3 letters (sham). Across the
5 subgroups, the treatment effect ranged from +5.0 to +14.6 letters. The mean
number of ranibizumab injections was 5.8 (ranibizumab arm) with no new ocular or
nonocular adverse events. CONCLUSION: Ranibizumab 0.5 mg resulted in clinically
significant treatment effect versus sham at Month 2. Overall, ranibizumab was
effective in treating choroidal neovascularization of various etiologies with no
new safety findings.
PMID- 28704255
TI - CHOROIDAL VASCULAR HYPERPERMEABILITY AS A PREDICTOR OF TREATMENT RESPONSE FOR
POLYPOIDAL CHOROIDAL VASCULOPATHY.
AB - PURPOSE: To investigate the influence of choroidal vascular hyperpermeability
(CVH) and choroidal thickness on treatment outcomes in eyes with polypoidal
choroidal vasculopathy (PCV) undergoing anti-vascular endothelial growth factor
monotherapy or combination therapy of photodynamic therapy and anti-vascular
endothelial growth factor injections. METHODS: The authors performed a
prospective, observational cohort study involving 72 eyes of 72 patients with
polypoidal choroidal vasculopathy (mean age 68.6 years, 51% men) treated with
either monotherapy (n = 41) or combination therapy (n = 31). Each eye was imaged
with color fundus photography, fluorescent angiography, indocyanine green
angiography, and spectral domain optical coherence tomography. Indocyanine green
angiography images were used to evaluate CVH, and spectral domain optical
coherence tomography was used to measure central choroidal thickness. Changes in
visual acuity over 12 months, and number of anti-vascular endothelial growth
factor injections were investigated. RESULTS: Choroidal vascular
hyperpermeability was present in 31 eyes (43.1%). Visual acuity change over 12
months was numerically better in the CVH group compared with the CVH (-) group (
0.099 and -0.366 logarithm of the minimal angle of resolution unit in the CVH (-)
and CVH (+) groups, respectively, multivariate P = 0.063) and significantly
better in a matched pair analysis (P = 0.033). Furthermore, in the combination
therapy group, the number of injection was significantly lower in the CVH (+)
group compared with the CVH (-) group (4.68 vs. 2.58 injections/year in the CVH (
) and CVH (+) groups; P = 0.0044). There was no significant relationship between
treatment response and choroidal thickening. CONCLUSION: The presence of CVH is
associated with better visual outcome in eyes with polypoidal choroidal
vasculopathy and lower injection number in combination therapy. Thus, CVH, but
not choroidal thickness, should be further evaluated as a potential biomarker for
selecting patients for combination therapy.
PMID- 28704256
TI - Associations Between Pedometer-Determined Physical Activity and Adiposity in
Children and Adolescents: Systematic Review.
AB - OBJECTIVE: The present review sought to examine the evidence on the associations
between pedometer-determined physical activity and adiposity. DESIGN: Of 304
potentially eligible articles, 36 were included. A search for observational
studies was carried out using Cochrane Library (CENTRAL), the OVID (MEDLINE,
Embase, and PsycINFO), EBSCOhost (Sportdiscus), and PEDro database from their
commenced to July 2015. Of 304 potentially eligible articles, 36 were included.
RESULTS: Most studies (30/36; 83%) were cross sectional and all used proxies for
adiposity, such as body mass index (BMI) or BMI z-score as the outcome measure.
Few studies (2/36; 6%) focused on preschool children. There was consistent
evidence of negative associations between walking and adiposity; significant
negative associations were observed in 72% (26/36) of studies overall.
CONCLUSIONS: The present review supports the hypothesis that higher levels of
walking are protective against child and adolescent obesity. However, prospective
longitudinal studies are warranted; there is a need for more research on younger
children and for more "dose-response" evidence.
PMID- 28704257
TI - The combination of CYP3A4*22 and CYP3A5*3 single-nucleotide polymorphisms
determines tacrolimus dose requirement after kidney transplantation.
AB - INTRODUCTION: Tacrolimus (Tac) has a narrow therapeutic window and shows large
between-patient pharmacokinetic variability. As a result, over-immunosuppression
and under-immunosuppression are frequently encountered in daily clinical
practice. Unraveling the impact of genetic polymorphisms on Tac pharmacokinetics
may help to refine therapy. In this study, the associations of single-nucleotide
polymorphisms (SNPs) in drug-metabolizing enzymes (CYP3A) with Tac
pharmacokinetics were investigated in renal transplant recipients. PARTICIPANTS
AND METHODS: In a cohort of 272 kidney transplant recipients, associations
between functional genetic variants (CYP3A4*22 and CYP3A5*3) and dose-adjusted
predose Tac concentrations (C0) and daily doses of Tac at days 5-7 and 15 and 1,
3, 6 and 12 months after renal transplantation were evaluated. Patients were
genotyped and clustered according to both CYP3A4*22 and CYP3A5*3 allelic status:
poor (PM) (CYP3A4*22 carriers with CYP3A5*3/*3), intermediate (IM) (CYP3A4*1/*1
with CYP3A5*3/*3 or CYP3A4*22 carriers with CYP3A5*1 carriers) and extensive
CYP3A-metabolizers (EM) (CYP3A4*1/*1 and CYP3A5*1 carriers). RESULTS: EM had an
88% lower dose-adjusted C0 compared with IM. PM had a 26% higher dose-adjusted C0
compared with IM. The percentage of patients with supratherapeutic Tac exposure
(C0>15 ng/ml) was significantly higher in PM (43.5%) compared with EM (0%) at
days 5-7 after transplantation (P=0.01). About 30% of EM had subtherapeutic
exposure (C0<5 ng/ml) at days 5-7 after transplantation (P=0.001). CONCLUSION:
The combined CYP3A4 and CYP3A5 genotype of renal transplant recipients has a
major influence on the Tac dose required to reach the target exposure.
PMID- 28704258
TI - Effect of alternating standing and sitting on blood pressure and pulse wave
velocity during a simulated workday in adults with overweight/obesity.
AB - OBJECTIVE: Reducing prolonged sitting at work has been recommended by an expert
panel, but whether intermittent standing improves vascular health is unclear. We
aimed to test whether using a sit-stand desk could reduce blood pressure (BP) and
pulse wave velocity (PWV) during a simulated workday. METHODS: Overweight/obese
adults with pre-to-Stage 1 hypertension completed a randomized crossover study
with two simulated workday conditions: STAND-SIT (alternating standing and
sitting condition every 30 min) and SIT (continuous sitting condition).
Oscillometric BP was measured hourly. Carotid-femoral, carotid-radial, and
carotid-ankle PWV were measured in the morning, mid-day, and late afternoon using
tonometry. RESULTS: Participants [n = 25, 64% male, 84% white, mean (SD) age: 42
(12) years] had average resting SBP of 132 (9) mmHg and DBP of 83 (8) mmHg. In
linear mixed models, STAND-SIT resulted in a significantly lower DBP (mean +/-
SE: -1.0 +/- 0.4 mmHg, P = 0.020) and mean arterial pressure (MAP) (-1.0 +/- 0.4
mmHg, P = 0.029) compared with SIT. SBP (-0.9 +/- 0.7 mmHg, P = 0.176) was not
different across conditions. Carotid-ankle PWV was significantly lower during the
STAND-SIT vs. SIT condition (-0.27 +/- 0.13 m/s, P = 0.047), whereas carotid
femoral PWV (-0.03 +/- 0.13 m/s, P = 0.831) and carotid-radial PWV (-0.30 +/-
0.18 m/s, P = 0.098) were not. Changes in MAP partially explained changes in PWV.
CONCLUSION: Interrupting prolonged sitting during deskwork with intermittent
standing was a sufficient stimulus to slightly, but statistically significantly,
decrease DBP, MAP, and carotid-ankle PWV. Though the clinical significance of the
observed effects is modest, regular use of a sit-stand desk may be a practical
way to lower BP and PWV while performing deskwork.
PMID- 28704259
TI - Systemic blood pressure at exercise in hypoxia in hypertensive and normotensive
patients.
AB - OBJECTIVES: The current study aimed to determine whether acute hypoxia exposure
in laboratory conditions associated with exercise induces an increase in systemic
blood pressure (BP) in normotensive and hypertensive patients, and whether
hypertensive patients are more prone to develop severe acute mountain sickness
(sAMS). Finally, to determine if BP changes at exercise in acute hypoxia in
hypertensive patients are predictive factors for sAMS. METHODS: From 2012 to
2015, 852 normotensive and 106 hypertensive patients went through an acute
hypoxia exercise test before a sojourn at high altitude. A subgroup of 228
normotensive was selected to match age, sex ratio, body weight and BMI and
compared with the hypertensive group. RESULTS: In normotensive and hypertensive
patients, for a given workload, BP was higher in hypoxia than in normoxia,
whereas, for a given heart rate, it was lower in hypoxia than in normoxia.
Hypertensive patients treated by beta-blockers showed lower arterial oxygen
saturation (vs. other treatments) and blunted cardiac and ventilatory responses
to hypoxia at exercise. Based on questionnaires filled out at high altitude,
hypertensive patients were not more prone than normotensive patients to develop
sAMS. During the laboratory acute hypoxic exercise test, hypertensive patients
suffering from sAMS, although taking acetazolamide showed similar BP than
hypertensive patients without sAMS and without acetazolamide. DISCUSSION AND
CONCLUSION: We hypothesize that acute hypoxia with exercise in laboratory
conditions induces a peripheral vasodilation that balances vasoconstriction and
tachycardia centrally induced through the adrenergic system. Hypertensive and
normotensive patients behave similarly during exercise in acute hypoxia. Acute
hypoxia does not exacerbate the exercise-induced increase in BP. BP variation,
during the acute hypoxia exercise test, is not a useful predictor of intolerance
to high altitude. Based on laboratory tests in acute hypoxia, hypertensive
patients may not be at higher risk to develop sAMS at high altitude.
PMID- 28704260
TI - alpha-Solanine reverses pulmonary vascular remodeling and vascular angiogenesis
in experimental pulmonary artery hypertension.
AB - OBJECTIVE: Similar to cancer, pulmonary arterial hypertension (PAH) is
characterized by vascular remodeling, which leads to obliteration of the small
pulmonary arteriole, with marked proliferation of pulmonary artery smooth muscle
cells (PASMC) and/or endothelial cells dysfunction. Aberrant expression of tumor
suppressor genes is closely associated with susceptibility to PAH. We
hypothesized that alpha-solanine, a glycoalkaloid found in members of the
nightshade family known to have antitumor activity in different cancers, reverses
experimental PAH by activating the tumor suppressor-axis inhibition protein 2
(AXIN2). METHODS AND RESULTS: We investigated the effects of alpha-solanine on
PASMC proliferation and apoptosis by using 5-ethynyl-2'-deoxyuridine
proliferation assay, proliferating cell nuclear antigen and Ki67 staining, TUNEL
and Anexine V assays. Scratch wound healing and tube formation assays were also
used to study migration of endothelial cells. In vitro, we demonstrated, using
cultured human PASMC from PAH patients, that alpha-solanine reversed
dysfunctional AXIN2, beta-catenin and bone morphogenetic protein receptor type-2
signaling, whereas restored [Ca]i, IL-6 and IL-8, contributing to the decrease of
PAH-PASMC proliferation and resistance to apoptosis. Meanwhile, alpha-solanine
inhibits proliferation, migration and tube formation of PAH-pulmonary artery
endothelial cells by inhibiting Akt/GSK-3alpha activation. In vivo, alpha
solanine administration decreases distal pulmonary arteries remodeling, mean
pulmonary arteries pressure and right ventricular hypertrophy in both
monocrotaline-induced and Sugen/hypoxia-induced PAH in mice. CONCLUSION: This
study demonstrates that AXIN2/beta-catenin axis and Akt pathway can be
therapeutically targeted by alpha-solanine in PAH. alpha-Solanine could be used
as a new therapeutic strategy for the treatment of PAH.
PMID- 28704261
TI - No independent association between pulse wave velocity and dementia: a population
based, prospective study.
AB - OBJECTIVE: Carotid-femoral pulse wave velocity (CFPWV), a marker of aortic
stiffness, has been associated with cognitive test results and markers of
cerebral small vessel disease, but its association with dementia has not been
studied in detail. Our aim was to assess the association of CFPWV with prevalent
and incident dementia in a large population-based study. METHODS: In total, CFPWV
was measured in 3056 participants of the Malmo Diet and Cancer study 2007-2012
(age range 61-85 years). Individuals scoring below preset cut-offs on cognitive
screening tests were thoroughly evaluated for prevalent dementia. Also, dementia
diagnoses were retrieved from the Swedish National Patient Register up until 31
December 2014, and then validated through medical records and neuroimaging
findings. RESULTS: We identified 159 cases of dementia, of which 57 were
classified as prevalent, and 102 as incident during a median follow-up of 4.6
years. In fully adjusted logistic regressions, CFPWV was not associated with
prevalent all-cause dementia (odds ratio 0.95 per 1 m/s increase in CFPWV, 95%
confidence interval 0.83-1.08), and it did not predict incident all-cause
dementia (odds ratio 1.00, 95% confidence interval 0.91-1.09). Neither was CFPWV
associated with subtypes of dementia (Alzheimer's disease, vascular dementia,
mixed dementia), although the number of cases in subgroups were low. CONCLUSION:
No independent association was found between CFPWV and dementia. It remains a
matter of debate why CFPWV repeatedly has been associated with cognitive test
results and markers of cerebral small vessel disease, but not with dementia.
PMID- 28704262
TI - Effect of upper body position on arterial stiffness: influence of hydrostatic
pressure and autonomic function.
AB - OBJECTIVE: To evaluate changes in arterial stiffness with positional change and
whether the stiffness changes are due to hydrostatic pressure alone or if
physiological changes in vasoconstriction of the conduit arteries play a role in
the modulation of arterial stiffness. METHODS: Thirty participants' (male = 15,
24 +/- 4 years) upper bodies were positioned at 0, 45, and 72 degrees angles.
Pulse wave velocity (PWV), cardio-ankle vascular index, carotid beta-stiffness
index, carotid blood pressure (cBP), and carotid diameters were measured at each
position. A gravitational height correction was determined using the vertical
fluid column distance (mmHg) between the heart and carotid artery. Carotid beta
stiffness was calibrated using three methods: nonheight corrected cBP of each
position, height corrected cBP of each position, and height corrected cBP of the
supine position (theoretical model). Low frequency systolic blood pressure
variability (LFSAP) was analyzed as a marker of sympathetic activity. RESULTS:
PWV and cardio-ankle vascular index increased with position (P < 0.05). Carotid
beta-stiffness did not increase if not corrected for hydrostatic pressure.
Arterial stiffness indices based on Method 2 were not different from Method 3 (P
= 0.65). LFSAP increased in more upright positions (P < 0.05) but diastolic
diameter relative to diastolic pressure did not (P > 0.05). CONCLUSION: Arterial
stiffness increases with a more upright body position. Carotid beta-stiffness
needs to be calibrated accounting for hydrostatic effects of gravity if measured
in a seated position. It is unclear why PWV increased as this increase was
independent of blood pressure. No difference between Methods 2 and 3 presumably
indicates that the beta-stiffness increases are only pressure dependent, despite
the increase in vascular sympathetic modulation.
PMID- 28704263
TI - Facebook advertising for participant recruitment into a blood pressure clinical
trial.
AB - OBJECTIVES: Recruitment of sufficient sample size into clinical trials is
challenging. Conventional advertising methods are expensive and are often
ineffective. The effectiveness of Facebook for recruitment into blood pressure
clinical trials of middle-to-older-aged people is unknown. This study aimed to
assess this by comparing Facebook advertising with conventional recruitment
methods from a retrospective analysis within a clinical trial. METHODS:
Conventional advertisements (newspaper, radio and posters) were employed for the
first 20 months of a randomized controlled clinical trial conducted in three
Australian capital cities from Tasmania, Queensland and the Australian Capital
Territory. With dwindling participant recruitment, at 20 months a Facebook
advertising campaign was employed intermittently over a 4-month period.
Recruitment results were retrospectively compared with those using conventional
methods in the previous 4 months. RESULTS: Compared with conventional recruitment
methods, Facebook advertisement was associated with a significant increase in the
number of participants recruited in the Australian Capital Territory (from an
average 1.8-7.3/month; P < 0.05). There was also an increase in Tasmania that was
of borderline significance (from 4.0 participants recruited/month to 9.3/month; P
= 0.052). However, there was no effect in Queensland (from 6.0 participants
recruited/month to 3.0/month; P = 0.15). Facebook advertisement was associated
with a significant decrease in the age of participants enquiring into the study
(from 60.9 to 58.7 years; P < 0.001). CONCLUSION: Facebook advertising was
successful in helping to increase recruitment of middle-to-older aged
participants into a blood pressure clinical trial, although there may be some
variability in effect that is dependent on location.
PMID- 28704264
TI - Extravascular renal denervation ameliorates juvenile hypertension and renal
damage resulting from experimental hyperleptinemia in rats.
AB - BACKGROUND: Material obesity in rodents is associated with neonatal
hyperleptinemia and hypertension of sympathetic origin in adult offspring.
Previously, we reported that experimentally induced hyperleptinemia in rat pups
results in adulthood hypertension. Here, we addressed the hypothesis that
experimental neonatal hyperleptinemia, through renal nerve activation, adversely
affects adult renal function. METHOD: Sprague-Dawley male and female pups were
treated with neonatal leptin (3 mg/kg, intraperitoneal) or neonatal saline, twice
daily from postnatal day 9-14. Juvenile (1 month) neonatal leptin and neonatal
saline rats were subjected to either bilateral renal denervation, unilateral
renal denervation or Sham surgery. Arterial pressure was telemetrically
monitored. RESULTS: Juvenile neonatal leptin rats with intact renal nerves
demonstrated increased mean arterial pressure (MAP) accompanied by local renin
angiotensin system overactivity and reduced glomerular filtration rate. Bilateral
renal denervation in rats protected against neonatal leptin-induced MAP, renal
renin-angiotensin system and impaired glomerular filtration rate. A two-fold
increase in sympathetically mediated tubulointerstitial damage in young adult (2
months) neonatal leptin females, was suppressed by unilateral renal denervation,
independent of MAP. Neonatal leptin rats also demonstrated increases in urinary
protein, neutrophil gelatinase-associated lipocalin, and kidney injury molecule
1. Raised blood pressure was associated with increased salt sensitivity and with
sustained renal dysfunction in adulthood. CONCLUSION: We propose that neonatal
hyperleptinemia programmes long-term renal structural and functional damage,
through renal sympathetic nerve activation.
PMID- 28704265
TI - Limits of stability in patients with vascular (due to diabetes) and nonvascular
unilateral transtibial amputation: a cross-sectional study.
AB - The aim of the study was to investigate the differences in the stability limits
between patients with vascular and nonvascular unilateral transtibial amputation
(UTA) and patients without amputation. Eighteen patients with UTA who used a
prosthesis were divided into two groups: vascular (n=9) and nonvascular (n=9).
Twenty-four patients without amputation served as the control group. Computerized
dynamic posturography Smart EquiTest System, version 8.0 was used for measuring
stability limits. The limits of stability test was used to assess the
participants' ability to voluntarily sway to various locations in space. The
measured parameters were maximum centre of gravity (COG) excursion, endpoint COG
excursion and directional control. Single-factor analysis of variance and
Bonferroni adjustment a posteriori tests was performed to investigate the
differences between groups. The patients with vascular UTA had significantly
lower endpoint COG excursion to oblique and forward direction compared with
controls (P=0.017). In addition, the patients with vascular UTA had significantly
lower maximum COG excursion to oblique and forward and to oblique and backward
directions (P=0.031; 0.019). Patients with vascular UTA had significantly lower
endpoint and maximum COG excursion to oblique and backward direction compared
with patients with nonvascular UTA (P=0.30; 0.029). To summarize, patients with
vascular UTA have substantially reduced limits of stability compared with
patients without amputation and the patients with nonvascular UTA.
PMID- 28704266
TI - Electrical stimulation therapy for dysphagia: a follow-up survey of USA dysphagia
practitioners.
AB - The aim of this study was to compare current application, practice patterns,
clinical outcomes, and professional attitudes of dysphagia practitioners
regarding electrical stimulation (e-stim) therapy with similar data obtained in
2005. A web-based survey was posted on the American Speech-Language-Hearing
Association Special Interest Group 13 webpage for 1 month. A total of 271 survey
responses were analyzed and descriptively compared with the archived responses
from the 2005 survey. Results suggested that e-stim application increased by 47%
among dysphagia practitioners over the last 10 years. The frequency of weekly e
stim therapy sessions decreased while the reported total number of treatment
sessions increased between the two surveys. Advancement in oral diet was the most
commonly reported improvement in both surveys. Overall, reported satisfaction
levels of clinicians and patients regarding e-stim therapy decreased. Still, the
majority of e-stim practitioners continue to recommend this treatment modality to
other dysphagia practitioners. Results from the novel items in the current survey
suggested that motor level e-stim (e.g. higher amplitude) is most commonly used
during dysphagia therapy with no preferred electrode placement. Furthermore, the
majority of clinicians reported high levels of self-confidence regarding their
ability to perform e-stim. The results of this survey highlight ongoing changes
in application, practice patterns, clinical outcomes, and professional attitudes
associated with e-stim therapy among dysphagia practitioners.
PMID- 28704267
TI - Effect of a brief motivational intervention in reducing alcohol consumption in
the emergency department: a randomized controlled trial.
AB - BACKGROUND: Introduction to alcohol consumption early in life increases the risk
of alcohol dependency and hence motivational interventions are needed in young
patients visiting the emergency department (ED). AIM: This study aims to
investigate the efficacy of a brief motivational intervention in reducing alcohol
consumption among young ED patients. PATIENTS AND METHODS: This was a blind
randomized controlled trial with follow-up at 3 months. Patients were stratified
on the basis of age and blood alcohol level of 0.5 g/l or more. A total of 263
patients aged 16-24 were randomized, with 132 patients in the brief motivational
intervention group and 131 in the control group, with data collection at 3
months. From September 2011 to July 2012, a psychologist performed the brief
motivational intervention 5 days after the patients' discharge. A phone call was
made at 1 and 2 months. The control group received a self-assessment leaflet. The
reduction in consumption was determined on the basis of the number of drinks
consumed in the last week prior to the survey. RESULTS: The mean reduction
between number of drinks at baseline and number of drinks at 3 months in the
control group was 0.3 and that in the intervention group was 0.9. This reduction
in alcohol use in the brief motivational intervention group was not significant.
The study did not show an association between brief motivational intervention and
repeated drunkenness [relative risk (RR): 0.99, 95% confidence interval (CI):
0.79-1.24], alcohol consumption at least once a month (RR: 0.81, 95% CI: 0.31
2.10) and alcohol consumption at least 10 times during the month (RR: 1.1, 95%
CI: 0.96-1.26). CONCLUSION: We did not observe a significant decrease in alcohol
consumption among the youth. Further studies are needed to confirm the positive
impact of a brief motivational intervention in the ED.
PMID- 28704268
TI - Safe discharge and outpatient investigation of ureteric colic: a retrospective
analysis.
AB - BACKGROUND: Computed tomography of the kidneys, ureters and bladder is the
recommended imaging modality for suspected urolithiasis. Early scanning is
advised in guidelines, but there is limited published evidence to support this
recommendation. PATIENTS AND METHODS: In a retrospective study, we reviewed
patients managed according to a local guideline. Patients without high-risk
features were either imaged during their initial visit (if in the daytime) or
discharged for outpatient scans. Complications, unplanned returns, final
diagnosis, and intervention rates were compared between groups. RESULTS: Fifty
four patients were scanned during their initial visit and 151 were scanned as an
outpatient at a median interval of 10 days. Unplanned return rates were lower in
those scanned as outpatients (7.3 vs. 24.1%), with no significant difference in
complications (2.0 vs. 3.7%; none leading to permanent harm). Those scanned as
outpatients were less likely to have a stone proven by imaging (39.7 vs. 64.8%),
but did not have a significantly higher rate of proven alternative diagnosis (9.3
vs. 13.0%). CONCLUSION: There is no evidence in this cohort that discharging
patients for outpatient imaging is associated with poorer outcomes, provided that
an appropriate clinical risk assessment is carried out.
PMID- 28704269
TI - The impact of medical specialist staffing on emergency department patient flow
and satisfaction.
AB - OBJECTIVE: The aim of this study was to describe the impact of additional medical
specialists, non-emergency physicians (non-EPs), performing direct supervision or
a combination of direct and indirect supervision at an EP-led emergency
department (ED), on patient flow and satisfaction. PATIENTS AND METHODS: An
observational, cross-sectional, three-part study was carried out including staff
surveys (n=379), a before and after 16-week data collection using data of visits
during the peak hours (n=5270), and patient questionnaires during 1 week before
the pilot and during week 5 of the pilot. Content analysis and descriptive
statistics were used for analyses. RESULTS: The value of being present at the ED
was acknowledged by medical specialists in 49% of their surveys and 35% of the
EPs' and ED nurses' surveys, especially during busy shifts. Radiologists were
most often (67.3%) convinced of their value of being on-site, which was agreed
upon by the ED professionals. Perceived improved quality of care, shortening of
length of stay, and enhanced peer consultation were mentioned most often.During
the pilot period, length of stay of boarded patients decreased from 197 min
(interquartile range: 121 min) to 181 min (interquartile range: 113 min,
P=0.006), and patient recommendation scores increased from -15 to +20.
CONCLUSION: Although limited by the mix of direct and indirect supervision, our
results suggest a positive impact of additional medical specialists during busy
shifts. Throughput of admitted patients and patient satisfaction improved during
the pilot period. Whether these findings differ between direct supervision and
combination of direct and indirect supervision by the medical specialists
requires further investigation.
PMID- 28704270
TI - Impact of Ramadan on emergency department visits and on medical emergencies.
AB - BACKGROUND: Fasting during Ramadan is important to Muslims. This study describes
changes in emergency department (ED) visits and in frequencies of emergency
conditions and impact on clinical outcomes during Ramadan in a tertiary care
center in Beirut, Lebanon. PATIENTS AND METHODS: Patients presenting to ED during
Ramadan 1 month before and 1 month after Ramadan over a 3-year period with
specific conditions (acute coronary syndrome, stroke, seizure, diabetes, renal
colic, headache or hypertension) were included. Clinical and sociodemographic
characteristics, ED volume, diagnoses, and outcomes were examined during two
periods (Ramadan vs. non-Ramadan). Multiple logistic regressions were performed
to identify the impact of Ramadan on ED bounce-back and mortality at ED
discharge. RESULTS: A total of 3536 patients were included. The daily average ED
volume was higher during non-Ramadan months (145.65+/-22.14) compared with
Ramadan (128.85+/-14.52). The average ED length of stay was higher during Ramadan
(5.42+/-14.86 vs. 3.96+/-4.29 h; P=0.006). Frequencies and admission rates for
the selected diseases were comparable during the two periods, except for patients
with acute coronary syndrome or stroke who had lower admission rates during
Ramadan.ED bounce-back rates and mortality at ED discharge were higher during
Ramadan (odds=1.34, 95% confidence interval: 1.03-1.74 and odds ratio=2.88, 95%
confidence interval: 1.01-8.27, respectively). CONCLUSION: EDs might experience a
decrease in volumes, higher length of stay, and potentially worse outcomes during
Ramadan. Changes in the frequencies of ED visits related to common conditions are
not expected. Prospective studies documenting fasting status would clarify
further the impact of Ramadan.
PMID- 28704271
TI - Mitigation of adverse behavioral impact from predator exposure by the
nociceptin/orphanin FQ peptide antagonist J-113397 in rats.
AB - The nociceptin/orphanin FQ peptide (NOP) receptor is believed to have an integral
modulatory function in the stress response system. We evaluated the highly
selective NOP antagonist J-113397 (7.5 and 20.0 mg/kg), using a predator exposure
in which rats were exposed to predator cats as a stressor. A single dose of J
113397 or vehicle was administered (intraperitoneally) shortly before exposure to
the predators or a sham exposure. Behavioral impact was measured using elevated
plus maze (EPM), open field activity (OFA), and an olfactory discrimination (OD).
The predator exposure produced a relatively long-lasting deficit (decreased time
in open arms, decreased basic activity) on the EPM while having little effect on
performance on the OFA or OD. J-113397 mitigated the performance deficits on the
EPM in a dose-dependent manner while having little effect on performance on the
OFA or OD. The largest dose of J-113397, administered with a sham exposure, was
essentially devoid of effects on the EPM, OFA, and OD. These results demonstrate
that J-113397 can significantly and selectively mitigate the effects of a
stressor typically used in a preclinical model of post-traumatic stress disorder.
Furthermore, these results are consistent with and extend previous results
showing that the NOP receptor has an important role in the response to stress and
that NOP antagonism may, potentially, have therapeutic benefit in stress
disorders.
PMID- 28704272
TI - Epigenetic mechanisms associated with addiction-related behavioural effects of
nicotine and/or cocaine: implication of the endocannabinoid system.
AB - The addictive use of nicotine (NC) and cocaine (COC) continues to be a major
public health problem, and their combined use has been reported, particularly
during adolescence. In neural plasticity, commonly induced by NC and COC, as well
as behavioural plasticity related to the use of these two drugs, the involvement
of epigenetic mechanisms, in which the reversible regulation of gene expression
occurs independently of the DNA sequence, has recently been reported.
Furthermore, on the basis of intense interactions with the target
neurotransmitter systems, the endocannabinoid (ECB) system has been considered
pivotal for eliciting the effects of NC or COC. The combined use of marijuana
with NC and/or COC has also been reported. This article presents the addiction
related behavioural effects of NC and/or COC, based on the common
behavioural/neural plasticity and combined use of NC/COC, and reviews the
interacting role of the ECB system. The epigenetic processes inseparable from the
effects of NC and/or COC (i.e. DNA methylation, histone modifications and
alterations in microRNAs) and the putative therapeutic involvement of the ECB
system at the epigenetic level are also discussed.
PMID- 28704273
TI - Anxiety does not contribute to social withdrawal in the subchronic phencyclidine
rat model of schizophrenia.
AB - Social withdrawal should not be considered a direct measure of the negative
symptoms of schizophrenia as it may result not only from asociality (primary
negative symptom) but also from other altered processes such as anxiety. To
understand the contribution of these two factors to social deficit, we
investigated whether the social withdrawal observed in the subchronic
phencyclidine (PCP) rat model of schizophrenia could be attributed to increased
anxiety. Compared to saline controls, PCP-treated rats (5 mg/kg, twice daily for
7 days, followed by a washout period) spent significantly less time in social
interaction, but did not show anxiety-like behaviors in different relevant
behavioral paradigms. In addition, their social deficit was not affected by a
behavioral procedure known to reduce anxiety-like behavior (repeated exposure to
the same partner) nor by systemic administration of the classical anxiolytic
diazepam. In contrast, PCP-induced social withdrawal was reversed by the
cannabinoid agonist CP55,940, a drug with known anxiogenic properties.
Furthermore, when using the social approach task, PCP-treated animals performed
similarly to control animals treated with diazepam, but not to those treated with
the anxiogenic compound pentylenetetrazole. Taken together, our results indicate
that PCP-induced social withdrawal cannot be attributed to increased anxiety.
These data are discussed in the context of primary versus secondary negative
symptoms and the deficit syndrome of schizophrenia.
PMID- 28704274
TI - Maternal separation induces long-term effects on monoamines and brain-derived
neurotrophic factor levels on the frontal cortex, amygdala, and hippocampus:
differential effects after a stress challenge.
AB - The maternal separation (MS) paradigm is a well-known animal model that resembles
the stress of early adverse life experiences and produces structural and
functional abnormalities when animals are adults. The present study analyzed the
effect of MS, in adult mice, on brain-derived neurotrophic factor (BDNF),
serotonin (5-HT), and dopamine (DA) levels, and the turnover rate in the
hippocampus, frontal cortex, and amygdala, and brain regions that are associated
with emotion. Also, the effects of MS in depression-like responses in adult mice
were studied. The results showed that MS from postnatal day 8-21 induces
depression-like behaviors. In MS mice, the three brain areas showed differential
responses in 5-HT, DA, and BDNF concentrations both in basal levels and when
animals were challenged with an acute stressor in adulthood. Specifically, under
basal conditions, MS increased monoamine and BDNF levels in the hippocampus and
amygdala, but decreased these levels in the frontal cortex. In MS, but not in
control mice, the amygdala responded to the stress challenge, whereas the frontal
cortex showed no response. Finally, the hippocampus showed increased 5-HT and DA
activity, but not increased BDNF after the stress challenge in MS mice. The
present results support the theory of the hypofunctionality of the frontal cortex
and hyperactivity of mesolimbic areas in depression-like conditions.
PMID- 28704275
TI - Agonist E-6837 and antagonist SB-271046 of 5-HT6 receptors both reverse the
depressive-like effect induced in mice by subchronic ketamine administration.
AB - Major depression is one of the most common affective disorders caused by
schizophrenia. The administration of N-methyl-D-aspartate receptor antagonists,
such as ketamine, can reproduce the negative and affective symptoms of this
disorder in animals. Preclinical studies have shown that 5-HT6 receptor (5-HT6R)
agonists and antagonists have a considerable antipsychotic response. The aim of
the present study was to evaluate the effect of an acute treatment with an
agonist, E-6837, and an antagonist, SB-271046, of 5-HT6R on the immobility
induced in mice by a subchronic ketamine regimen (5 days; 10 mg/kg/day,
intraperitoneal). Repeated ketamine administration alone increased the immobility
time in the forced-swimming test and the tail-suspension test. E-6837 at 10 and
20 mg/kg caused a significant reduction of immobility in the tail-suspension test
and forced-swimming test, respectively. Interestingly, SB-271046 (10 mg/kg) also
elicited an antidepressant-like effect in both tests. The current findings
suggest an important role for these 5-HT6R ligands as mood modulators. However,
it is necessary to explore the physiological mechanisms involved in this process
in greater detail.
PMID- 28704276
TI - Effects of D1 and D2 receptor antagonists on the discriminative stimulus effects
of methylendioxypyrovalerone and mephedrone in male Sprague-Dawley rats trained
to discriminate D-amphetamine.
AB - Psychopharmacology research has amassed substantial evidence for similarities
between synthetic cathinones and other commonly abused psychostimulants. Few
studies have utilized drug discrimination methods to investigate synthetic
cathinones, and the precise neurochemical substrates underlying their
interoceptive effects have not been examined. The present study assessed the
involvement of D1 and D2 dopaminergic receptors in the stimulus effects of 3,4
methylenedioxypyrovalerone (MDPV) and mephedrone (MEPH) in rats trained to
discriminate D-amphetamine. Eight male Sprague-Dawley rats were trained to
discriminate 0.5 mg/kg D-amphetamine (AMPH) from saline. Dose-response curves
were then generated with AMPH (0.0-1.0 mg/kg), MDPV (0.0-1.0 mg/kg), and MEPH
(0.0-2.0 mg/kg). Subsequently, Sch 39166 (0.3 mg/kg) and haloperidol (0.5 mg/kg)
were administered in combination with select doses of MDPV and MEPH. Both MDPV
and MEPH produced full substitution for AMPH. Sch 39166 produced a downward shift
in the MDPV and MEPH dose-response curves and haloperidol produced similar
results with MDPV. These preliminary findings indicate that MDPV and MEPH produce
interoceptive stimuli that are similar to those produced by AMPH and that D1 and
D2 dopamine receptors contribute to these effects. Additional studies are
warranted to investigate the contribution of other receptor mechanisms involved
in the interoceptive stimuli produced by synthetic cathinones.
PMID- 28704277
TI - Effects of ceftriaxone on conditioned nicotine reward in rats.
AB - Nicotine is the addictive compound in tobacco products which exerts psychosomatic
effects that contribute to abuse and to low rates of abstinence in treatment
seeking smokers. At present, the most successful smoking cessation aide helps one
in four individuals quit smoking at 1 year postcessation. New adjunctive
therapies are needed to improve status of smoking-related public health crises,
and beta-lactam antibiotics are one class of potential therapies as they
favorably augment extrasynaptic glutamate clearance. Our study used two-chamber
place conditioning to assess effects of ceftriaxone (CTX) on persistence of
conditioned nicotine reward. Rats were conditioned to associate nicotine (0.4
mg/kg, subcutaneous) with one context and vehicle with an alternative context.
After initial post-test, rats received either daily ceftriaxone (200 mg/kg,
intraperitoneal) or saline. All rats showed nicotine place preference during post
test 1. CTX-treated rats meeting extinction criterion by post-test 7 showed
significantly reduced preference for the nicotine-paired context during post-test
2 compared with vehicle-treated rats. We interpret these data to support the
further study of CTX as a smoking cessation aide. Our results suggest that CTX
reduces persistence of conditioned nicotine reward and may be helpful for
improving abstinence rates in a subset of treatment-seeking smokers.
PMID- 28704278
TI - Trace amine-associated receptor 1 agonists RO5263397 and RO5166017 attenuate
quinpirole-induced yawning but not hypothermia in rats.
AB - Increasing evidence suggests that trace amine-associated receptor 1 (TAAR1) is an
important modulator of the dopaminergic system. Existing molecular evidence
indicates that TAAR1 regulates dopamine levels through interactions with dopamine
transporters and D2 receptors. However, investigations to date have not been
exhaustive and other pathways may be involved. In this study, we used a well
described set of behaviors, quinpirole-induced yawning and hypothermia, to
explore the potential interaction of TAAR1 and D3 receptors, which are members of
the 'D2-like' dopamine receptor subfamily. Previous studies have shown that for
D2/D3 receptor agonists, the induction of yawning is a D3 receptor-mediated
effect, whereas the inhibition of yawning and induction of hypothermia are D2
receptor-mediated effects. Quinpirole produced an inverted U-shaped dose-effect
curve for yawning, which was shifted downward dose-dependently by each of the
TAAR1 agonists RO5263397 and RO5166017. Quinpirole also produced dose-dependent
hypothermia, which was not affected by either TAAR1 agonist. These results
suggest that TAAR1 agonists may interact with D3 receptors and/or its downstream
pathways, as opposed to D2 receptors. These findings may shed light on a
previously unexplored possibility for the mechanism of TAAR1-mediated effects.
PMID- 28704279
TI - Assessing healthcare professionals' experiences of integrated care: do surveys
tell the full story?
AB - BACKGROUND: Integrated care is the combination of different healthcare services
with the goal to provide comprehensive, seamless, effective and efficient patient
care. Assessing the experiences of healthcare professionals (HCPs) is an
important aspect when evaluating integrated care strategies. AIMS: The aim of
this rapid review was to investigate if quantitative surveys used to assess HCPs'
experiences with integrated care capture all the aspects highlighted as being
important in qualitative research, with a view to informing future survey
development. METHODS: The review considered all types of health professionals in
primary care, and hospital and specialist services, with a specific focus on the
provision of integrated care aimed at improving the patient journey. PubMed,
CINAHL and grey literature sources were searched for relevant surveys/program
evaluations and qualitative research studies. Full text articles deemed to be of
relevance to the review were appraised for methodological quality using abridged
critical appraisal instruments from the Joanna Briggs Institute. Data were
extracted from included studies using standardized data extraction templates.
Findings from included studies were grouped into domains based on similarity of
meaning. Similarities and differences in the domains covered in quantitative
surveys and those identified as being important in qualitative research were
explored. RESULTS: A total of 37 studies (19 quantitative surveys, 14 qualitative
studies and four mixed-method studies) were included in the review. A range of
healthcare professions participated in the included studies, the majority being
primary care providers. Common domains identified from quantitative surveys and
qualitative studies included Communication, Agreement on Clear Roles and
Responsibilities, Facilities, Information Systems, and Coordination of Care and
Access. Qualitative research highlighted domains identified by HCPs as being
relevant to their experiences with integrated care that have not routinely being
surveyed, including Workload, Clear Leadership/Decision-Making, Management,
Flexibility of Integrated Care Model, Engagement, Usefulness of Integrated Care
and Collaboration, and Positive Impact/Clinical Benefits/Practice Level Benefits.
CONCLUSION: There were several domains identified from qualitative research that
are not routinely included in quantitative surveys to assess health
professionals' experiences of integrated care. In addition, the qualitative
findings suggest that the experiences of HCPs are often impacted by deeper
aspects than those measured by existing surveys. Incorporation of targeted items
within these domains in the design of surveys should enhance the capture of data
that are relevant to the experiences of HCPs with integrated care, which may
assist in more comprehensive evaluation and subsequent improvement of integrated
care programs.
PMID- 28704280
TI - The paradox of transient worsening renal function in patients with acute heart
failure: the role of B-type natriuretic peptide and diuretic response.
AB - AIMS: Worsening renal function (WRF) occurs in one-third of patients hospitalized
for acute decompensated heart failure. Recently, WRF was categorized in two
subtypes: persistent and transient WRF. Thus, we sought to investigate the
different prognostic impact of persistent vs. transient WRF; we also evaluate the
relation of two WRF phenotypes with congestion, B-type natriuretic peptide (BNP)
changes, and diuretic response at discharge. METHODS: The prospective was a
single centre study including patients screened for interventional Diur-heart
failure Trial (NCT01441245). Patients were eligible if they were admitted with a
primary diagnosis of acute heart failure with evidence of volume overload.
Persistent WRF was defined as a sustained creatinine increase by at least 0.3
mg/dl throughout the hospitalisation; transient WRF was defined as creatinine
increase by at least 0.3 mg/dl within 72 h and a return to baseline levels at
discharge. Patients were followed for 6 months after discharge. RESULTS: Our
population included 192 acute decompensated heart failure patients. In total, 61
patients developed persistent WRF and 29 developed transient WRF. Patients with
persistent WRF showed a lower mean urine output with respect to the transient WRF
group and patients with preserved renal function (1618 +/- 374 vs. 2132 +/- 392
vs. 2075 +/- 442 ml; P < 0.001). Similarly, patients with transient WRF
demonstrated a higher rate of BNP decrease more than 30% than seen in patients
with stable creatinine levels and in the persistent WRF group (95 vs. 76 vs. 54%;
P = 0.001). Univariate Cox regression analysis demonstrated that BNP decrease
less than 30% [HR 2.15 (1.40-3.40); P < 0.001] and persistent WRF [HR 1.70 (1.11
2.61); P = 0.01] were related to poor outcome; conversely, transient WRF should
be considered as a protective factor [HR 0.42 (0.19-0.93); P = 0.03]. In the
multivariable model, only persistent WRF appeared to be related to poor prognosis
[HR 1.61 (1.02-2.57); P = 0.04]. CONCLUSION: WRF occurring during hospitalization
has a different significance: transient deterioration appears to be associated
with a favourable clinical course; conversely, persistent WRF is related to poor
outcome.
PMID- 28704281
TI - The Diagnostic Value of 3-Dimensional Sampling Perfection With Application
Optimized Contrasts Using Different Flip Angle Evolutions (SPACE) MRI in
Evaluating Lower Extremity Deep Venous Thrombus.
AB - OBJECTIVES: The aim of this study was to evaluate the diagnostic performance of
noncontrast magnetic resonance imaging utilizing sampling perfection with
application optimized contrasts using different flip angle evolutions (SPACE) in
detecting deep venous thrombus (DVT) of the lower extremity and evaluating clot
burden. MATERIALS AND METHODS: This prospective study was approved by the
institutional review board. Ninety-four consecutive patients (42 men, 52 women;
age range, 14-87 years; average age, 52.7 years) suspected of lower extremity DVT
underwent ultrasound (US) and SPACE. The venous visualization score for SPACE was
determined by 2 radiologists independently according to a 4-point scale (1-4,
poor to excellent). The sensitivity and specificity of SPACE in detecting DVT
were calculated based on segment, limb, and patient, with US serving as the
reference standard. The clot burden for each segment was scored (0-3, patent to
entire segment occlusion). The clot burden score obtained with SPACE was compared
with US using a Wilcoxon test based on region, limb, and patient. Interobserver
agreement in assessing DVT (absent, nonocclusive, or occlusive) with SPACE was
determined by calculating Cohen kappa coefficients. RESULTS: The mean venous
visualization score for SPACE was 3.82 +/- 0.50 for reader 1 and 3.81 +/- 0.50
for reader 2. For reader 1, sensitivity/specificity values of SPACE in detecting
DVT were 96.53%/99.90% (segment), 95.24%/99.04% (limb), and 95.89%/95.24%
(patient). For reader 2, corresponding values were 97.20%/99.90%, 96.39%/99.05%,
and 97.22%/95.45%. The clot burden assessed with SPACE was not significantly
different from US (P > 0.05 for region, limb, patient). Interobserver agreement
of SPACE in assessing thrombosis was excellent (kappa = 0.894 +/- 0.014).
CONCLUSIONS: Non-contrast-enhanced 3-dimensional SPACE magnetic resonance imaging
is highly accurate in detecting lower extremity DVT and reliable in the
evaluation of clot burden. SPACE could serve as an important alternative for
patients in whom US cannot be performed.
PMID- 28704282
TI - Excessive Surgical Adhesive Mimicking Aortic Root Abscess: A Case Report.
AB - Aortic root abscess is a complication of aortic valve endocarditis that is
associated with a high morbidity and mortality. The diagnosis usually is made
with transesophageal echocardiography, which is highly sensitive and specific for
the disease. We present a case of suspected aortic root abscess 1 week after
mechanical aortic valve replacement for native valve endocarditis. The diagnosis
was made by the use of transesophageal echocardiography but surgical inspection
revealed that the paravalvular fluid collection was excessive surgical adhesive.
We discuss the clinical significance and differential diagnosis of aortic root
abscess in the setting of infective endocarditis.
PMID- 28704284
TI - Evaluation of a Simpler Tool to Assess Nontechnical Skills During Simulated
Critical Events.
AB - INTRODUCTION: Management of critical events requires teams to employ nontechnical
skills (NTS), such as teamwork, communication, decision making, and vigilance. We
sought to estimate the reliability and provide evidence for the validity of the
ratings gathered using a new tool for assessing the NTS of anesthesia providers,
the behaviorally anchored rating scale (BARS), and compare its scores with those
of an established NTS tool, the Anaesthetists' Nontechnical Skills (ANTS) scale.
METHODS: Six previously trained raters (4 novices and 2 experts) reviewed and
scored 18 recorded simulated pediatric crisis management scenarios using a
modified ANTS and a BARS tool. Pearson correlation coefficients were calculated
separately for the novice and expert raters, by scenario, and overall. RESULTS:
The intrarater reliability of the ANTS total score was 0.73 (expert, 0.57;
novice, 0.84); for the BARS tool, it was 0.80 (expert, 0.79; novice, 0.81). The
average interrater reliability of BARS scores (0.58) was better than ANTS scores
(0.37), and the interrater reliabilities of scores from novices (0.69 BARS and
0.52 ANTS) were better than those obtained from experts (0.47 BARS and 0.21 ANTS)
for both scoring instruments. The Pearson correlation between the ANTS and BARS
total scores was 0.74. CONCLUSIONS: Overall, reliability estimates were better
for the BARS scores than the ANTS scores. For both measures, the intrarater and
interrater reliability was better for novices compared with domain experts,
suggesting that properly trained novices can reliably assess the NTS of
anesthesia providers managing a simulated critical event. There was substantial
correlation between the 2 scoring instruments, suggesting that the tools measured
similar constructs. The BARS tool can be an alternative to the ANTS scale for the
formative assessment of NTS of anesthesia providers.
PMID- 28704285
TI - Cricothyroidotomy In Situ Simulation Curriculum (CRIC Study): Training Residents
for Rare Procedures.
AB - INTRODUCTION: Technical skill acquisition for rare procedures can be challenging
given the few real-life training opportunities. In situ simulation (ISS), a
training technique that takes place in the actual workplace, is a promising
method to promote environmental fidelity for rare procedures. This study
evaluated a simulation-based technical skill curriculum for cricothyroidotomy
using deliberate practice, followed by an ISS evaluation session. METHODS: Twenty
emergency medicine residents participated in a two-part curriculum to improve
cricothryoidotomy performance. A pretest established participant baseline
technical skill. The training session consisted of two parts, didactic teaching
followed by deliberate practice using a task-training manikin. A posttest
consisted of an unannounced, high-fidelity ISS, during an emergency department
shift. The primary outcome was the mean performance time between the pretest and
posttest sessions. Skill performance was also evaluated using a checklist scale
and global rating scale. RESULTS: Cricothyroidotomy performance time improved
significantly from pretest to posttest sessions (mean difference, 59 seconds; P <
0.0001). Both checklist and global rating scales improved significantly from the
pretest to the posttest with a mean difference of 1.82 (P = 0.002) and 6.87 (P =
0.0025), respectively. Postcourse survey responses were favorable for both the
overall curriculum experience and the unannounced ISS. CONCLUSIONS: This pilot
study demonstrated that unannounced ISS is feasible and can be used to
effectively measure cricothyroidotomy performance among EM residents. After a two
part training session consisting of didactic learning and deliberate practice,
improved cricothyroidotomy skill performance was observed during an unannounced
ISS in the emergency department. The integration of ISS in cricothyroidotomy
training represents a promising approach; however, further study is needed to
establish its role.
PMID- 28704286
TI - The Effect of Force Feedback in a Virtual Learning Environment on the Performance
and Satisfaction of Dental Students.
AB - INTRODUCTION: This study investigated the effect of force feedback (FFB) on
student performance in a virtual learning environment (VLE) using the Simodont
dental trainer (Moog, Nieuw-Vennep, the Netherlands) and evaluated the students'
satisfaction with and without FFB. METHODS: The Simodont dental trainer, which
was used as a VLE, was randomly assigned to 101 first-year dental students with
no previous experience in cutting a tooth or working in a VLE with FFB. This
study was designed as a crossover study. One half of the students practiced
without FFB, whereas one half practiced with FFB. Both groups practiced four
sessions lasting 45 minutes on a cross preparation. In the fifth session, test 1
was scheduled. After test 1, the same practicing and testing protocol was
followed, although the environment was switched. After test 2, participants
filled out a questionnaire. For the statistical analysis, only the questionnaires
of the students who participated in both tests were processed. RESULTS: The
results of test 1 and test 2 revealed that only students who used FFB were able
to pass the tests. The questionnaire outcomes supported the results of both
tests; 100% of the students preferred working with FFB. CONCLUSIONS: The results
suggest that FFB is important for performance in a VLE and essential for
satisfaction.
PMID- 28704287
TI - Developing Team Cognition: A Role for Simulation.
AB - STATEMENT: Simulation has had a major impact in the advancement of healthcare
team training and assessment. To date, most simulation-based training and
assessments focus on the teamwork behaviors that impact team performance, often
ignoring critical cognitive, motivational, and affective team processes. Evidence
from team science research demonstrates a strong relationship between team
cognition and team performance and suggests a role for simulation in the
development of this team-level construct. In this article, we synthesize research
from the broader team science literature to provide foundational knowledge
regarding team cognition and highlight best practices for using simulation to
target team cognition.
PMID- 28704288
TI - The Effectiveness of Medical Simulation in Teaching Medical Students Critical
Care Medicine: A Systematic Review and Meta-Analysis.
AB - STATEMENT: We aimed to assess effectiveness of simulation for teaching medical
students critical care medicine and to assess which simulation methods were most
useful. We searched AMED, EMBASE, MEDLINE, Education Resources Information
Centre, British Education Index, Australian Education Index, and bibliographies
and citations, in July 2013. Randomized controlled trials comparing effectiveness
of simulation with another educational intervention, or no teaching, for teaching
medical students critical care medicine were included. Assessments for inclusion,
quality, and data extraction were duplicated and results were synthesized using
meta-analysis.We included 22 randomized control trials (n = 1325). Fifteen
studies comparing simulation with other teaching found simulation to be more
effective [standardized mean difference (SMD) = 0.84; 95% confidence interval
(CI) = 0.43 to 1.24; P < 0.001; I = 89%]. High-fidelity simulation was more
effective than low-fidelity simulation, and subgrouping supported high-fidelity
simulation being more effective than other methods. Simulation improved skill
acquisition (SMD = 1.01; 95% CI = 0.49 to 1.53) but was no better than other
teaching in knowledge acquisition (SMD = 0.41; 95% CI = -0.09 to 0.91).
PMID- 28704289
TI - Beyond Fidelity: Deconstructing the Seductive Simplicity of Fidelity in Simulator
Based Education in the Health Care Professions.
AB - STATEMENT: Fidelity has become a ubiquitous feature of discourse in simulation
studies. Recent studies have highlighted the often ambiguous and contradictory
manner in which fidelity has been defined, with each definition emphasizing
different physical and functional features of simulation. We suggest that
regarding fidelity as an objective property of a simulation obscures the
interactive nature of the educator-learner relationship and should be abandoned.
Rather than conceiving training as tasks performed by an individual in isolation,
we suggest that it is more accurately understood as the social learning of
affordances. Affordances represent the functional features of a simulator, which
are taken as relevant in a specific learning context by means of analogy.
Training is successful to the extent that educators and learners share an
understanding of those affordances. Even when explicitly formulated, the concept
of fidelity has greater difficulty accounting for the complex, interactional
features of the training situation in comparison with accounts based on social
learning. We conclude that continued attempts to redefine and use fidelity in the
context of training will likely yield little benefit to the field compared with
an interactive social learning framework.
PMID- 28704290
TI - Developing a Conversational Virtual Standardized Patient to Enable Students to
Practice History-Taking Skills.
AB - INTRODUCTION: Although traditional virtual patient simulations are designed to
teach and assess clinical reasoning skills, few employ conversational dialogue
with the patients. The virtual standardized patients (VSPs) described herein
represent standardized patients that students interview using natural language.
Students take histories and develop differential diagnoses of the VSPs as much as
they would with standardized or actual patients. The student-VSP interactions are
recorded, creating a comprehensive record of questions and the order in which
they were asked, which can be analyzed to assess information-gathering skills.
Students document the encounter in an electronic medical record created for the
VSPs. METHODS: The VSP was developed by integrating a dialogue management system
(ChatScript) with emotionally responsive 3D characters created in a high-fidelity
game engine (Unity). The system was tested with medical students at the Ohio
State University College of Medicine. Students are able to take a history of a
VSP, develop a differential diagnosis, and document the encounter in the
electronic medical record. RESULTS: Accuracy of the VSP responses ranged from 79%
to 86%, depending on the complexity of the case, type of history obtained, and
skill of the student. Students were able to accurately develop an appropriate
differential diagnosis on the basis of the information provided by the patient
during the encounter. CONCLUSIONS: The VSP enables students to practice their
history-taking skills before encounters with standardized or actual patients.
Future developments will focus on creating an assessment module that will
automatically analyze VSP sessions and provide immediate student feedback.
PMID- 28704291
TI - National Clinical Skills Competition for Medical Students in China.
PMID- 28704292
TI - Improvement of higher brain dysfunction after brain injury by repetitive
transcranial magnetic stimulation and intensive rehabilitation therapy: case
report.
AB - Repetitive transcranial magnetic stimulation (rTMS) and intensive cognitive
rehabilitation (CR) were administered to two patients with cognitive dysfunction
following brain injury. The first case was a 67-year-old man who presented with
memory dysfunction, attention dysfunction, and decreased insight following
diffuse axonal injury. High-frequency rTMS (10 Hz, 2400 pulses/day) targeting the
anterior cingulate using a navigation system and CR were administered for 12 days
at 1 year from the onset of injury. The patient showed improved
neuropsychological performance and activities of daily living. In addition,
single photon emission computer tomography with Tc-ECD showed improved perfusion
in the anterior cingulate gyrus. The second case was a 68-year-old man who
presented with dysfunction of memory, attention, and executive function following
a cerebral infarction in the middle cerebral artery region within the right
hemisphere. This patient received 12 days (except for Sundays) of low-frequency
rTMS (1 Hz, 1200 pulses/day) targeting the left dorsolateral prefrontal cortex
and the left posterior parietal cortex and CR. Following this intervention, the
patient's neuropsychological performance and activities of daily living improved.
Furthermore, single photon emission computer tomography showed changes in
perfusion in the rTMS target sites and areas surrounding the targets. We have
shown the safety and efficacy of rTMS therapy using a navigation system combined
with intensive CR on two patients with cognitive dysfunction following brain
injury. In addition, we observed changes in the areas around the rTMS target
sites in brain imaging data.
PMID- 28704293
TI - Analysis of neural crest cells from Charcot-Marie-Tooth disease patients
demonstrates disease-relevant molecular signature.
AB - Charcot-Marie-Tooth disease (CMT) is the most common inherited neuropathy. The
majority of CMT is demyelinating type (demyelinating CMT) caused by Schwann cell
involvement. Although a large number of genes responsible for demyelinating CMT
have been found, the common molecular target of the pathophysiology caused by
these different genes in demyelinating CMT is still unknown. We generated induced
pluripotent stem cells (iPSCs) from healthy controls and patients with
demyelinating CMT caused by duplication in peripheral myelin protein 22 kDa
(PMP22) or point mutations in myelin protein zero (MPZ) or early growth response
2 (EGR2). iPSCs were differentiated into neural crest cells, progenitors of
Schwann cells, followed by purification using the neural crest cell markers p75
and human natural killer-1. To identify a disease-relevant molecular signature at
the early stage of demyelinating CMT, we conducted global gene expression
analysis of iPSC-derived neural crest cells and found that a glutathione-mediated
detoxification pathway was one of the related pathways in demyelinating CMT. mRNA
expression of glutathione S-transferase theta 2 (GSTT2), encoding an important
enzyme for glutathione-mediated detoxification, and production of reactive oxygen
species were increased in demyelinating CMT. Our study suggested that patient
iPSC-derived neural crest cells could be a cellular model for investigating
genetically heterogeneous disease CMT and might provide a therapeutic target for
the disease.
PMID- 28704294
TI - Early detection of neonatal hypoxic-ischemic white matter injury: an MR diffusion
tensor imaging study.
AB - The purpose of this study was to compare diffusion tensor metrics in normal age
matched neonates with survivors of hypoxic-ischemic encephalopathy (HIE) and
extracorporeal membrane oxygenation (ECMO). Thirty-five normal, 27 HIE, and 13
ECMO infants underwent MRI at 3 T. Neurodevelopmental assessments were performed.
Fractional anisotropy (FA), axial diffusivity (AD), and radial diffusivity (RD)
of the inferior fronto-occipital fasciculus, inferior longitudinal fasciculus,
anterior commissure, genu corpus callosum and splenium of the corpus callosum,
anterior and posterior limb of the internal capsule, superior longitudinal
fasciculus, and the centrum semiovale were analyzed with tract-based spatial
statistics modified for use in neonates. Linear regression analysis was
performed, and 95% confidence intervals were created for age effects on the
tensor metrics with the control patients. Two-sample t-test was done to determine
whether there was a difference in the tensor metrics between the normal and
patient cohort. There was a statistically significant age effect on the FA and RD
in the selected regions of the brain (F<0.05) and a group difference in the FA
and RD between the normal and the HIE group (P<0.05). The group difference in the
FA and RD between the normal and ECMO groups was seen in the anterior commissure,
genu corpus callosum, right inferior longitudinal fasciculus, fronto-occipital
fasciculus, centrum semiovale, and superior longitudinal fasciculus (P<0.05).
Patients who were outside the 95% confidence intervals of the FA, AD, and RD
overlapped with those with abnormalities clinically and on the conventional MRI.
In conclusion, diffusion tensor imaging can play a significant role in detecting
infants with early indications of hypoxic-ischemic brain injury.
PMID- 28704295
TI - Partially Pigmented Eyelid Basal Cell Carcinoma With Unusual Trabecular
Histologic Pattern.
PMID- 28704296
TI - Osteotomy as a treatment option in dysplasia epiphyseal hemimelica of the distal
radius: a case report.
AB - : Dysplasia epiphysialis hemimelica (DEH), also known as Trevor disease, is a
very rare disease characterized by an overgrowth of the osteocartilaginous
epiphyseal caused by unknown factors. The medial side of the epiphysis is
affected twice as often as the lateral side and more than one epiphysis was
affected in two-thirds of the cases. Only a few cases of DEH in the upper
extremities have been published, as the lower limb is usually the most affected,
especially in the bones of the ankle joint. The symptoms vary from little
significant deformities to symptomatic cases, pain, and decreased function
depending on the location and the size of the lesion. When surgery is indicated,
the complete excision of the lesion is the procedure of choice. If this is not
possible, because of the location or size of the lesion, a realignment osteotomy
may be necessary. We report the case of a 12-year-old patient with a distal
epiphysis DEH on the left radius, treated by wedge osteotomy realignment at the
level of the lesion with Kirschner wires. The clinical outcome of realignment
osteotomy of the radial epiphysis has been the correction of the deformity with a
normal and painless function of the wrist and hand. The case reported was an
extremely rare location in the distal radial epiphysis of DEH. We are aware of
only one case published previously with involvement of the distal radius in
children. The surgical treatment of realignment osteotomy without complete
removal of the lesion has enabled anatomical and functional improvement of the
joint as well as a reduction in lesion size. LEVEL OF EVIDENCE: Level IV case
report.
PMID- 28704297
TI - Surgical treatment of displaced pediatric lateral condyle fractures of the
humerus by the posterior approach.
AB - The surgical approach for open reduction and internal fixation of lateral condyle
fractures in children is controversial. Some authors recommend the lateral
approach to the elbow over the posterior approach because of theoretical concern
for injury to the vascular supply of the distal humerus and potential avascular
necrosis (AVN). The purpose of this retrospective case series study is to report
the outcomes of open reduction and internal fixation of displaced lateral condyle
fractures of the humerus by the posterior approach. Fifteen consecutive cases
were reviewed and the posterior approach resulted in minimal postoperative loss
of motion, no angular deformity, cosmetic scars, and no AVN. We support that AVN
occurs because of stripping of soft tissues from the lateral condyle fragment and
not the approach used. Stripping of soft tissues is not required when using the
posterior approach because of excellent visualization of the fracture reduction.
PMID- 28704298
TI - Titanium mesh cage as an alternative reconstruction method for epiphyseal-sparing
tumour resections in children.
AB - In this study, we introduced an alternative reconstruction option for epiphysis
sparing tumour resection in children. Eight patients with a malignant tumour in
the diaphysis or metaphysis-diaphysis junction of a long bone underwent epiphysis
sparing intercalary resection. Reconstruction was performed using a titanium mesh
cage filled with impacted cancellous bone allograft and autograft. A plate and
screws were used to supplement the fixation. At the last follow-up, union was
achieved in seven patients. Limb-length discrepancy occurred in three patients.
Functional scores revealed a good functional outcome. This technique may be an
alternative method for epiphyseal-sparing tumour resections in children.
PMID- 28704299
TI - Slipped capital femoral epiphysis in children younger than 10 years old: clinical
characteristics and efficacy of physeal-sparing procedures.
AB - We aimed to investigate the clinical characteristics of slipped capital femoral
epiphysis (SCFE) in patients aged less than 10 years and identify the efficacy of
physeal-sparing procedures in this age group. Demographic data of 18 SCFE
patients aged less than 10 years were compared with those of 71 older patients to
investigate the clinical characteristics. The efficacy of physeal-sparing
procedures (n=5) was investigated compared with that of in-situ screw fixation
(n=13). Obese children were noticeably more common among SCFE patients aged less
than 10 years (P=0.034). The slip angle improved significantly more in the
physeal-sparing subgroups (P=0.038) without the occurrence of further slippage.
Moreover, physeal-sparing procedures allow persistent growth of the proximal
femoral physis. However, most of the patients in the physeal-sparing subgroup
needed additional surgeries when the proximal femoral physis outgrew the implant.
Obesity may be associated more with early-onset SCFE (onset<10 years). Physeal
sparing procedures are safe and effective in preventing leg-length discrepancy
and allowing the remodeling of the deformed proximal femur in this age group.
PMID- 28704300
TI - Postinfectious heterotopic ossification of the ilium involving the iliacus
muscle.
AB - Heterotopic ossification in soft tissue or muscle is rare in the pediatric and
adolescent age group. Most cases are associated with musculoskeletal injury and
trauma to the central nervous system. Here, we describe an adolescent patient
without a history of trauma or lesions in the central nervous system who
presented with a painful limp with limited motion of the left hip. Investigations
indicated unusually large heterotopic ossification extending from the inner
aspect of the ilium down to the anterior part of the hip, highly likely to have
developed after an unrecognized periacetabular pyomyositis primarily involving
the iliacus muscle. Surgical excision was performed successfully without
perioperative complications. No recurrence was detected at the final follow-up.
PMID- 28704301
TI - Congenital unilateral absence of the upper extremity may give rise to a specific
kind of thoracolumbar curve.
AB - : There is an increased incidence of scoliosis in patients with congenital
malformations of the upper extremity even in the absence of overt vertebral
abnormalities. In this case series, we summarize the curve characteristics of
four patients presenting to two spine surgery clinics with unilateral amelia or
phocomelia and a progressive scoliotic curve with the apex on the side of
deficiency. All patients required orthopedic intervention for their curves.
Amelia and phocomelia are severe congenital malformations of the upper limb
affecting trunk balance and, conceivably, causing scoliosis with the absence of
counterbalancing weight on the affected side. The combination of upper limb
absence and same-sided scoliosis in these patients may provide a clue of the
mechanical factors causing scoliosis in other disorders. In this article, we
attempt to define this exceptional deformity, theorize on its etiology, and draw
attention to this particular combination of problems. LEVEL OF EVIDENCE: Case
series; Level IV.
PMID- 28704302
TI - Botulinum-A intramuscular injection in an orthopaedic paediatric patient cohort:
service restructure analysis.
AB - Botulinum intramuscular injections are increasingly being used in the management
of hypertonic musculature. Historically, injections were administered under
general anaesthesia (GA), which has service and economic implications. Our
delivery changed to outpatient conscious injections to improve service
efficiency. A retrospective analysis of all patient injections from January 2010
to December 2015 analysed cost-benefit and efficiency of service remodelling. 472
patients were administered injections, 298 in theatre under GA and 174 without
GA. In 2010, 97 of 102 cases were performed under GA (45 theatre-hours),
decreasing to 18 of 68 cases in 2015 (8.4 theatre-hours). The mean hospital stay
decreased from 410 to 135 min. The reduction in theatre use and the requirement
for a postanaesthetic bed led to significant savings per case. Service
remodelling showed successful cost saving and reduced in-hospital stay.
PMID- 28704303
TI - Gain of length-loss of strength? Alteration in muscle strength after femoral leg
lengthening in young patients: a prospective longitudinal observational study.
AB - This study aimed to determine the alteration in maximum isokinetic torque in
patients after intramedullary femoral leg lengthening. Thirty patients with a
median leg-length discrepancy of 3.0 cm underwent femoral limb lengthening with
an intramedullary motorized device. Maximum isokinetic, concentric torque of the
extensors, and flexors of the knee was measured before (n=30) and 2 years after
surgery (n=21). Postoperatively, a significant difference remained for the
maximum isokinetic torque of the extensors (22%) between the lengthened and the
normal leg, which might have been caused by muscle response to the distraction
procedure itself in the form of higher stiffness, less immediate displacement,
and inconsistent force relaxation properties. However, we provide evidence that
physiotherapy after limb lengthening should focus on extensors to prevent loss of
strength.
PMID- 28704304
TI - Arterial tree anomalies in patients with clubfoot: an investigation carried out
at Soba University Hospital.
AB - Vascular deficiencies and reduced perfusion of the anterior tibial artery and the
dorsalis pedis artery were suggested as causes of congenital talipes equino varus
(CTEV). In this study, we assessed the prevalence of arterial abnormalities in
patients with CTEV (50 patients; 74 feet) compared with a normal control group
(16 patients; 32 feet) by Doppler ultrasound and Ankle Brachial Index. The flow
was normal in the control group and was deficient in 39.19% of clubfoot patients.
In severe clubfoot cases, the deficiency was found to an extent of 76.67%. In
conclusion, the anterior tibial artery and dorsalis pedis artery are deficient in
CTEV patients; to avoid postoperative skin sloughing, arterial supply must be
protected using a judicious incision.
PMID- 28704305
TI - Titanium mesh cage as an alternative reconstruction method for epiphyseal sparing
tumor resections in children.
PMID- 28704306
TI - Reversal of Ticagrelor-Induced Arrhythmias and Cheyne-Stokes Respiration With
Aminophylline Infusion.
AB - Dyspnea and bradyarrhythmias are frequent adverse effects (AEs) of ticagrelor.
AEs commonly occur within the first week of therapy, are dose related and usually
mild, but sometimes they may cause drug discontinuation. Currently, the exact
mechanisms of ticagrelor-related AEs have not been definitively explained. In
addition to the prevalent theory of adenosine overload, other reasonable
mechanism like a direct central stimulation hypothesis was suggested. We present
a case of incessant Cheyne-Stokes respiration associated with heart rate
instability in patient with congestive heart failure and non-ST-segment elevation
myocardial infarction, supporting the use of aminophylline as a potential
reversal agent of ticagrelor-related AEs.
PMID- 28704307
TI - Acute Cardiopulmonary, Metabolic, And Neuromuscular Responses To Severe-Intensity
Intermittent Exercises.
AB - The purpose of this study was to compare cardiopulmonary, neuromuscular, and
metabolic responses to severe-intensity intermittent exercises with variable or
constant work rate. Eleven cyclists (28 +/- 5 years; 74 +/- 7 kg; 175 +/- 5 cm;
63 +/- 4 mL.kg.min) performed the following tests until exhaustion on separate
days: 1) an incremental test; 2) in random order, two constant work rate tests at
95% and 110% of the peak power for the determination of Critical Power (CP); 3) 2
4 tests for the determination of the highest power that still permits the
achievement of maximal oxygen uptake (PHIGH); and 4) two random severe-intensity
intermittent exercises. The last two sessions consisted of a constant work rate
(CWR) exercise performed at PHIGH or a decreasing work rate (DWR) exercise from
PHIGH until 105% of CP. Compared to CWR, DWR presented higher time to exhaustion
(635 +/- 223 vs. 274 +/- 65 s), time spent above 95% of VO2max (t95%VO2max) (323
+/- 227 vs. 98 +/- 65 s), and O2 consumed (0.97 +/- 0.41 vs. 0.41 +/- 0.11 L).
Electromyography amplitude (RMS) decreased for DWR but increased for CWR during
each repetition. However, RMS and VO2 divided by power output (RMS/PO and VO2/PO
ratio) increased in every repetition for both protocols, but to a higher extent
and slope for DWR. These findings suggest that the higher RMS/PO and VO2/PO ratio
in association with the longer exercise duration seemed to have been responsible
for the higher t95%VO2max observed during severe DWR exercise.
PMID- 28704308
TI - Fatigue In U12 Soccer-7 Players During Repeated One-Day Tournament Games - A
Pilot Study.
AB - The aim of this study was to describe and compare the distances and displacement
speeds of U12 Soccer-7 athletes during four tournament Soccer-7 games (TG) played
in less than 24-h (experimental condition) with those recorded during two league
Soccer-7 games (LG) with 24-h of rest prior to the match (control condition). Ten
participants (age = 10.3 +/- 0.5 years) were recruited for the study. Main data
analyzed during games included distance completed relative to match duration
(Drel), maximal velocity and distance completed at different running speeds
(including acceleration, deceleration, standing, walking, jogging, medium
intensity running, high-intensity running and sprinting). For data collection
during games, athletes wore a GPS unit. Different (p<0.05) mean playing time was
recorded during TG and LG (15.1 and 31.8 minutes/match, respectively). Drel
during the four TG was maintained between 85.7 +/- 8.5 m/min and 87.5 +/- 8.5
m/min (P>0.05) and during the two LG between 84.2 +/- 10.9 m/min and 87.5 +/- 9.9
m/min (P>0.05). Moreover, similar Drel was recorded during TG and LG (86.8 m/min
and 85.9 m/min, respectively). Compared to LG, during TG maximal velocity was
lower (23.0 km/h and 21.3 km/h, respectively; P<0.05). In addition, compared to
the last game of the tournament, in the preceding games the distance covered at
low speeds (3.1-8.0 km/h) was lower (37.7% and 32.4%, respectively; P<0.05) and
at high speeds (>=18.1 km/h) tend to be higher (2.5% and 3.3%, respectively).
Therefore, compared with the control condition, accumulated Soccer-7 games with
less than 24-h of inter-day rest negatively affects displacement speeds
distribution (but not overall relative distances) in U12 Soccer-7 athletes. These
results may help to better plan training and competition schedules to youth
players.
PMID- 28704309
TI - Effect of Three Different Muscle Action Training Protocols on Knee Strength
Ratios and Performance.
AB - Ruas, CV, Brown, LE, Lima, CD, Costa, PB, and Pinto, RS. Effect of three
different muscle action training protocols on knee strength ratios and
performance. J Strength Cond Res 32(8): 2154-2165, 2018-Hamstring to quadriceps
(H:Q) ratios are often used to assess strength imbalances. The aims of this study
were to compare 3 different muscle action training protocols on H:Q strength
balance and functional performance. Forty untrained men (age: 22.87 +/- 2.28
years, mass: 70.66 +/- 11.049 kg, ht: 174.29 +/- 6.90 cm) performed 6 weeks of
training on an isokinetic dynamometer. They were randomly assigned to one of 4
groups; concentric quadriceps and concentric hamstring (CON/CON), eccentric
quadriceps and eccentric hamstring (ECC/ECC), concentric quadriceps and eccentric
hamstring (CON/ECC), or no training. Mixed Factor analyses of variance were used
to compare interactions for variables pretest and posttest between groups (p <=
0.05). The ECC/ECC group showed significant increases in H:Q functional ratio
(pre = 0.73 +/- 0.092, post = 0.87 +/- 0.098), ECC peak torque (PT) (pre = 226.44
+/- 67.80 N.m, post = 331.74 +/- 54.44 N.m), isometric PT (IPT) (pre = 173.69 +/-
41.41 N.m, post = 203.091 +/- 30.82 N.m), countermovement jump (CMJ) (pre = 52.73
+/- 6.95 cm, post = 58.16 +/- 6.10 cm), and drop jump (DJ) (pre = 52.91 +/- 6.080
cm, post = 58.20 +/- 7.72 cm), whereas the CON/CON group increased the rate of
torque development (pre = 152.19 +/- 65.0074 N.m.s, post = 225.26 +/- 88.80
N.m.s). There were no differences between groups for CON PT, squat jump,
conventional ratio or 40 m sprint. Our findings suggest that ECC/ECC training may
be the most effective at increasing functional H:Q strength ratios, as well as
ECC PT, IPT, CMJ, and DJ performance. Eccentric training increases ECC PT,
thereby increasing the functional H:Q ratio. Eccentric training also improves
vertical jumping involving ECC actions. CON/CON training may be more effective at
increasing explosive muscle strength.
PMID- 28704310
TI - The influence of contextual factors on running performance in female Australian
Football match-play.
AB - Given the recent growth of the professional status among multiple female football
codes, the aim of this study is to investigate the effects of contextual factors
on activity profiles and pacing strategies in female Australian football players.
Thirty-five female Australian football players participated in this study. Global
positioning system analysis was completed over one competitive season. Matches
were separated into eight 10-minute periods. Greater distances were covered
during the first half irrespective of playing position (ES = 0.39-0.50,
Likelihood >=90%). Throughout a number of periods half-backs (defensive players)
covered greater distances during losses (ES >=0.74, Likelihood >=92%) and against
Top 3 opponents (ES >=1.0, Likelihood >= 97%). Midfielders and half-backs covered
greater distances (ES >= 0.49, Likelihood >=89%) in the final match period in
winning compared with losing matches. A reduction in player work-rate is evident
during the second half of matches. The influence of contextual factors varied
across positional groups. However, it is clear coaches could use player rotation
both early in the match in an attempt to delay the effect of fatigue and more
frequently during the second half to increase running intensity.
PMID- 28704311
TI - Acute neuromuscular and endocrine responses to two different compound exercises:
squat versus deadlift.
AB - Anecdotally, it is believed that the deadlift exercise brings about greater
levels of central fatigue than other exercises; however no empirical evidence
exists to support this view. Additionally, little is known about the acute
endocrine response to heavy deadlift exercise and how this may differ to other
similar compound exercises. Therefore, the aim of this study was to identify and
compare the acute, neuromuscular and endocrine responses to squat and deadlift
exercise. Ten resistance trained males completed 8 sets of 2 repetitions at 95 %
of one repetition maximum. Maximum voluntary isometric knee extensor force
(MVIC), along with measures of central (voluntary activation (VA) and surface
electromyography (EMG)) and peripheral (electrically evoked control stimulus)
fatigue were made prior to and 5 and 30 min post-exercise. Additionally, salivary
testosterone and cortisol were measured at these same time points. MVIC was
reduced after the completion of both exercises (p = 0.007) however no difference
between exercises was evident. Similarly, although VA changed over time (p =
0.0001) no difference was observed between exercises. As a measure of peripheral
fatigue, force from the control stimulus changed over time (p = 0.003) with a
greater decrease evident after the squat (p = 0.034). EMG was reduced over time
(p = 0.048) but no difference was seen between exercises. No change was seen in
testosterone and cortisol. Even though a greater absolute load and larger volume
load was completed for the deadlift, no difference in central fatigue was evident
between the two compound exercises. The greater peripheral fatigue observed after
squat exercise may be due to the greater work completed by the quadriceps with
this exercise. These results suggest that separate periodization, tapering and
programming considerations may be unnecessary when using the squat and deadlift
to develop muscular strength.
PMID- 28704312
TI - Trunk muscle activation in the back and hack squat at the same relative loads.
AB - The hack squat (HS) is likely to produce a greater 1 repetition maximum (1RM)
compared to the back squat (BS). This can be attributed to the support of the
trunk during the HS compared to no support during BS. This support however, may
compromise trunk muscle activation (TMA), therefore producing different training
adaptations. Accordingly, the purpose of this study was to compare 1RM in BS and
HS and TMA at 4 relative loads, 65, 75, 85 and 95% of maximal system mass. Ten
males completed 3 test sessions:1) BS and HS 1RM, 2) HS & BS neuromuscular test
familiarization, and, 3) Neuromuscular test for 3 reps at 4 loads for BS and HS.
BS TMA was significantly greater (p<0.05) than HS for all muscles and phases
except rectus abdominus in concentric phase. TMA increased (p<0.05) with load in
all muscles for both exercises and phases apart from lumbar sacral erector spinae
in HS eccentric phase. Mean HS 1RM and submaximal loads were significantly
(p<0.0001) higher than the equivalent BS loads. Duration of the eccentric phase
was higher (p<0.01) in HS than BS but not different in concentric phase. Duration
increased significantly (p<0.01) with load in both exercises and both phases.
Despite higher absolute tests loads in HS, TMA was higher in BS. TMA is sensitive
to load in both exercises. BS is more effective than HS in activating the muscles
of the trunk and therefore arguably more effective in developing trunk strength
and stability for dynamic athletic performance.
PMID- 28704313
TI - Between-game variation of physical soccer performance measures in highly trained
youth soccer players.
AB - To assess the between-game variation in measures of physical performance during
11 v 11 soccer match-play, over a short period of time, in highly trained youth
soccer players. A single cohort observational study design was employed. Physical
match performance data were collected from 17 male, highly trained youth soccer
players (age: 13.3 +/- 0.4 y) over three, 2 x 20min, 11 v 11 matches. Using 10 Hz
GPS, the variables selected for analyses were total distance (TD), high-speed
running (HSR), very high-speed running (VHSR), number of high-speed running
efforts (HSReff) and number of very high-speed running efforts (VHSReff). Match
data was also separated into cumulative 5 min epochs, to identify the peak 5 min
epoch and the mean of the cumulative 5 min epochs for each match. Variability was
quantified using the coefficient of variation (CV), Standard error of measurement
(SEM) and intra-class correlation coefficient (ICC). Between- and within-player
smallest worthwhile changes (SWC) were also calculated for each variable to aid
in the interpretation of the data. Analysis of the variance between games
reported a low CV for TD (3.8%) but larger CVs for HSR (33.3%), HSReff (35.4%)
and VHSR and VHSReff (59.6 and 57.4 %, respectively). Analysis of 5 min epochs
(peak and average) found an increase in the CVs beyond that of the values
reported for the whole match. Between-player SWC in high intensity physical
performance data ranged from 24.7 - 42.4 %, whereas within-player SWC ranged from
1.2 - 79.9%. The between-game variability of high and very high intensity
activities in youth soccer players, across three soccer matches over a short
period of time (2 weeks), is relatively 'large' and specific to the individual,
thus highlighting the need for caution when interpreting physical performance
data between games and players.
PMID- 28704314
TI - Visual feedback attenuates mean concentric barbell velocity loss, and improves
motivation, competitiveness, and perceived workload in male adolescent athletes.
AB - It is unknown whether instantaneous visual feedback of resistance training
outcomes can enhance barbell velocity in younger athletes. Therefore, the purpose
of this study was to quantify the effects of visual feedback on mean concentric
barbell velocity in the back squat, and to identify changes in motivation,
competitiveness, and perceived workload. In a randomised-crossover design
(Feedback vs. Control) feedback of mean concentric barbell velocity was or was
not provided throughout a set of 10 repetitions in the barbell back squat.
Magnitude-based inferences were used to assess changes between conditions, with
almost certainly greater differences in mean concentric velocity between the
Feedback (0.70 +/-0.04 m.s) and Control (0.65 +/-0.05 m.s) observed.
Additionally, individual repetition mean concentric velocity ranged from possibly
(repetition number two: 0.79 +/-0.04 vs. 0.78 +/-0.04 m.s) to almost certainly
(repetition number 10: 0.58 +/-0.05 vs. 0.49 +/-0.05 m.s) greater when provided
feedback, while almost certain differences were observed in motivation,
competitiveness, and perceived workload, respectively. Providing adolescent male
athletes with visual kinematic information while completing resistance training
is beneficial for the maintenance of barbell velocity during a training set,
potentially enhancing physical performance. Moreover, these improvements were
observed alongside increases in motivation, competitiveness and perceived
workload providing insight into the underlying mechanisms responsible for the
performance gains observed. Given the observed maintenance of barbell velocity
during a training set, practitioners can use this technique to manipulate
training outcomes during resistance training.
PMID- 28704315
TI - Appetite regulations after sprint exercise under hypoxic condition in female
athletes.
AB - The present study determined changes in appetite-regulating hormones and energy
intake after high-intensity interval exercise (HIIT) under hypoxic conditions in
trained female athletes. Fifteen female athletes completed three trials on
different days of either HIIT under hypoxic conditions (HYP), HIIT under normoxic
conditions (NOR), or rest in normoxia (CON). Exercise trials consisted of two
successive sets of eight repeated bouts of a 6-s maximal sprint separated by a 30
s rest. Blood samples were obtained to measure plasma acylated ghrelin, glucagon
like peptide-1 (GLP-1), and metabolite concentrations. Energy intake during an ad
libitum buffet meal test was evaluated 30 min after exercise or rest. Plasma
acylated ghrelin concentrations decreased significantly after exercise (P <
0.001), but no difference was observed between the HYP and NOR. Plasma GLP-1
concentrations did not differ after exercise, with no difference between the HYP
and NOR. Although absolute energy intake in the HYP (634 +/- 67 kcal) and NOR
(597 +/- 63 kcal) was significantly lower than that in the CON (756 +/- 63 kcal,
P = 0.006), no difference was observed between the HYP and NOR. These results
show that HIIT under hypoxic and normoxic conditions lowered plasma acylated
ghrelin concentrations and energy intake.
PMID- 28704316
TI - Effects of a Tapering Period on Physical Condition in Soccer Players.
AB - The aim of this research was to analyze the effects of a two-week step tapering
period on lower-limb muscle power, change of direction (COD) and acceleration
capacities, and on the stress-recovery state in an amateur soccer team. Twenty
two male players were included in the study. Following a six-week progressive
training, the sample was divided into: experimental group (n = 11), who did a two
week period of taper in which training volume was 50% reduced (intensity was kept
high) and control group (n = 11), which kept on with the training. Muscle power
(countermovement jump test), acceleration (10m sprint test), COD (Illinois test)
and stress and recovery perceptions (RESTQ questionnaire) were evaluated before
training, at the end of it (pre-tapering, PRE-TP) and after the tapering period
(post-tapering, POST-TP). Following the taper, the experimental group in
comparison to the control group showed significantly improved power (1029.71 +/-
108.51 W/kg vs. 1084.21 +/- 110.87 W/kg; p < 0.01), acceleration (1.72 +/- 0.09 s
vs. 1.67 +/- 0.07 s; p < 0.05), and lower stress levels (1.9+/-0.5 vs. 1.6+/-0.5;
p < 0.01) (PRE-TP vs. POST-TP, respectively). COD did not show significant
changes. In conclusion, a two-week step tapering program was found to be an
effective periodization strategy to increase muscle power and acceleration, and
to reduce stress perception in soccer amateur players.
PMID- 28704317
TI - Comparison of Collagen Cross-Linking and Amniotic Membrane Transplantation in an
Experimental Alkali Burn Rabbit Model.
AB - PURPOSE: To compare the effects of collagen cross-linking (CXL) and amniotic
membrane transplantation (AMT) on acute corneal alkali burns. METHODS: After
establishment of an alkali burn model, 32 rabbits were divided into 4 groups:
control group, AMT group, CXL group, and AMT + CXL (combined) group. Clinical
parameters, including epithelial wound, opacity, ulceration, and
neovascularization, were evaluated on postinjury days 1, 7, 14, and 18.
Histological parameters were examined in hematoxylin/eosin (H&E) and Masson
trichrome-stained corneal sections. Immunohistochemical analyses, including a
terminal deoxynucleotidyl transferase-mediated biotin-deoxyuridine triphosphate
nick-end labeling assay and cluster of differentiation 68 (CD68) labeling, were
performed to determine the apoptotic index and macrophage activation. RESULTS: On
postinjury day 18, the epithelial wound of AMT {4.08% [interquartile range (IQR),
0.68%-5.22%]}, CXL [1.84% (IQR, 0.01%-3.89%)], and combined [3.44% (IQR, 0.01%
4.36%)] groups were significantly lower than the control [15.23% (IQR, 9.86%
23.06%)] group (P = 0.003). No significant difference was detected between the
groups in terms of opacity (P = 0.303). Neovascularization was the least severe
in the CXL group [16.18% (IQR, 8.39%-21.28%)] and the most severe in the AMT
[34.47% (IQR, 17.71%-62.77%)] and combined [35.12% (IQR, 31.96%-59.98%)] groups
on day 18 (P = 0.033). Significant increases in the apoptotic index and CD68
labeling were detected in the CXL and combined groups compared with those in the
control group (P = 0.047 and P = 0.001, respectively). CONCLUSIONS: CXL treatment
is an effective adjuvant treatment for promoting reepithelialization, reducing
inflammation and neovascularization, and preventing ulceration in acute alkali
burns. Providing AMT after suppressing inflammation may be a more effective
treatment.
PMID- 28704318
TI - Interrelationships Between 3 Keratoconic Cone Parameters.
AB - PURPOSE: To find out the interrelationships between 3 parameters of the
keratoconic cone. METHODS: A total of 101 keratoconic eyes of 58 patients were
included in this retrospective case series study. A complete eye examination was
performed. Kmax (K) and pachymetry at the thinnest point (T) were obtained from
the Pentacam tomographer. The vertex to thinnest pachymetry distance (D for
decentration) was calculated using trigonometry. Pearson correlation coefficients
between T and D, between T and K, and between D and K were calculated. RESULTS:
There is a statistically significant positive correlation between thinnest point
pachymetry and decentration (R = 0.366, P = 0.0002) and also statistically
significant negative correlation between thinnest point pachymetry and Kmax (R =
0.719, P < 0.00001) and decentration and Kmax (R = -0.281, P = 0.0044).
CONCLUSIONS: The interrelationships between the 3 keratoconic cone parameters
suggest that the thinner cones are largely central, that is, decenter less, but
show greater steepening.
PMID- 28704319
TI - Topical Tacrolimus for Corneal Subepithelial Infiltrates Secondary to Adenoviral
Keratoconjunctivitis.
AB - PURPOSE: The objective of this study was to determine the efficacy and safety of
topical tacrolimus compounded in the Pharmacy Service for the treatment of
subepithelial corneal infiltrates (SEIs) secondary to adenoviral
keratoconjunctivitis. METHODS: This retrospective study included patients who had
been dispensed topical tacrolimus for the treatment of SEIs during the previous
year. Patients were treated with tacrolimus 0.03% eye drops twice daily or
tacrolimus 0.02% ointment once daily. The following data were recorded: length of
treatment, visual acuity before and after treatment, intraocular pressure before,
during, and at the end of treatment, previous treatments, and the presence of
SEIs after treatment. The subjective symptoms of the patients were also assessed.
RESULTS: Fifty-five patients (85 eyes) were included, 54.5% with bilateral
involvement. A total of 31 (36.5%) eyes were treated with tacrolimus ointment and
54 eyes (63.5%) with tacrolimus eye drops. The median length of treatment was 185
days (p25-75: 93.5-426), and the mean follow-up duration was 363 days (p25-75:
148-540). In 62.35% of the eyes, the SEIs were reduced in number and size, and in
31.76%, they were eliminated. The patients had better visual acuity after
treatment with highly statistically significant differences. Tolerance was good
overall, being better in the eye drops group. CONCLUSIONS: Topical tacrolimus,
compounded in the pharmacy, seems to be an effective and safe alternative for the
treatment of SEIs secondary to adenovirus keratoconjunctivitis.
PMID- 28704320
TI - Recurrence Rate and Graft Stability With Fibrin Glue Compared With Suture and
Autologous Blood Coagulum for Conjunctival Autograft Adherence in Pterygium
Surgery: A Meta-Analysis.
AB - PURPOSE: To minimize recurrence and improve graft stability after pterygium
surgery, conjunctival autograft adherence is done using fibrin glue (FG) or
autologous blood coagulum (ABC). But there are studies that have reported
conflicting or inconclusive results. This meta-analysis was conducted to evaluate
the postoperative recurrence rate and graft stability after using FG, sutures,
and ABC. METHODS: MEDLINE, Cochrane databases, and ICTRP were searched and PRISMA
guidelines as well as recommended meta-analysis practices were followed. The odds
ratio was calculated to estimate the effect size to assess the difference in
recurrence and graft stability between the groups. Heterogeneity across the
studies was explored using subgroup analyses and quality assessment using the
Cochrane risk of bias tool and sensitivity analysis. RESULTS: After screening, 30
studies were included for meta-analysis. The random model analysis for recurrence
revealed an effect size of 0.44 [95% confidence interval (CI), 0.32-0.60], and
subgroup analysis for studies comparing FG and sutures showed an effect size of
0.38 (95% CI, 0.27-0.53). In case of studies comparing FG and ABC, the random
model analysis revealed an effect size of 1.01 (95% CI, 0.45-2.26). The random
model analysis for graft stability revealed an effect size of 0.87 (95% CI, 0.57
1.31). In subgroup analysis, the random model revealed an effect size of 0.39
(95% CI, 0.17-0.88) indicating significant better graft stability with FG over
ABC. CONCLUSIONS: This meta-analysis reveals the superiority of FG over sutures
as the use of FG can significantly reduce the recurrence rate, but no significant
difference in graft stability was found between FG and sutures. No significant
difference was found in the recurrence rate between FG and ABC, but graft
stability was found to be better with FG compared with ABC.
PMID- 28704321
TI - Observation of Retrocorneal Plaques in Patients With Infectious Keratitis Using
Anterior Segment Optical Coherence Tomography.
AB - PURPOSE: Endothelial plaques are a typical characteristic in patients with fungal
keratitis. However, bacterial keratitis and herpetic keratouveitis are rarely
associated with fibrin formation on the retrocorneal surface. This study was
conducted to examine plaques attached to the endothelium in patients with
infectious keratitis using anterior segment optical coherence tomography (AS
OCT). METHODS: Seventeen patients (10 women and 7 men; mean age, 75 +/- 15.5
years) suspected to have infectious keratitis with retrocorneal plaques were
included. AS-OCT was used to acquire a scan of the retrocorneal plaque at the
patient's first visit. RESULTS: Based on the culture results and detection of
viral DNA, the patients were diagnosed with fungal keratitis (6 patients),
bacterial keratitis (8 patients), and herpetic keratouveitis (3 patients).
Examination of the cornea using AS-OCT showed a clear boundary between the
corneal endothelial surface and plaque in 8 patients with bacterial keratitis and
in all patients with herpetic keratitis. Moreover, a space between the corneal
endothelial surface and plaque was found in 3 patients with bacterial keratitis.
In 5 patients with fungal keratitis, the AS-OCT images showed an unclear boundary
between the corneal endothelial surface and plaque, and high reflection of the
plaque was extended from the corneal lesion. CONCLUSIONS: Endothelial plaques in
patients with fungal keratitis could continue from the corneal lesion.
Observation of retrocorneal plaques using AS-OCT could be used in the diagnosis
of infectious keratitis.
PMID- 28704322
TI - Malignant Bowel Obstruction in Relapsed Ovarian Cancer With Peritoneal
Carcinomatosis: An Occlusive State.
AB - OBJECTIVE: The aim of this study was to describe the clinical and oncological
outcomes of women with malignant bowel obstruction (MBO) for relapsed ovarian
cancer and peritoneal carcinomatosis. METHODS: A retrospective cohort study was
performed in all consecutive patients admitted at Instituto Valenciano de
Oncologia, Valencia, Spain, between July 2013 and July 2016 with MBO for relapsed
ovarian cancer and peritoneal carcinomatosis. All patients underwent the same
protocol of conservative management. Surgical treatment was indicated only in
selected cases. RESULTS: There were a total of 22 patients presenting 59 episodes
of MBO; 17 (77.2%) of those patients presented more than 1 episode of MBO. All
patients had serous epithelial ovarian cancer; 18 (81.8%) were high grade, and 4
(18.2%) low-grade tumors. The median (range) number of episodes per patient was 3
(range, 1-7) with a mean length of hospitalization of 13 (SD, 13.6) days. The
median time interval between episodes of MBO (54 episodes in 17 patients) was 17
days (range, 1-727 days). Twenty of 22 patients died with a median overall
survival time from the first episode of MBO of 95 days (95% confidence interval,
49-124 days). CONCLUSIONS: Patients with MBO due to relapsed epithelial ovarian
cancer in the peritoneal carcinomatosis setting have a short life expectancy,
presenting a median of 3 episodes of MBO until death, with a short time interval
between episodes. These findings show that bowel obstruction can represent a
constant status over time until death.
PMID- 28704323
TI - Time Trends in the Incidence and Mortality of Ovarian Cancer in Ireland, Northern
Ireland, and Israel, 1994-2013.
AB - OBJECTIVES: The aims of this study were to compare time trends in ovarian cancer
incidence and mortality in populations with (1) similar genetics but different
health care systems (Ireland and Northern Ireland [NI]) and (2)different genetics
but similar health care system (Israeli Jews and Arabs) and to interpret the
results. METHODS: Age-standardized rates of ovarian cancer incidence and
mortality for 1994-2013 in the 3 countries were obtained from national cancer
registries and national statistics. Time trends in incidence, mortality, and
incidence-to-mortality ratio were assessed by linear regression models applied to
each country and between populations (Ireland-NI, Ireland-Israeli Jews, Israeli
Jews-Arabs). Joinpoint analysis was used to calculate the annual percentage
change (APC). RESULTS: Ovarian cancer incidence and mortality rates in 1994 were
similar in the countries studied. Thereafter a reduction in incidence and
mortality was observed in Ireland (incidence APC1994-2013 = -0.75%, P < 0.05;
mortality APC1994-2013 = -0.67%, P < 0.05), NI (incidence APC1998-2013 = -1.5%, P
< 0.05; mortality APC2005-2013 = -3.8%, P < 0.05), and Israeli Jews (incidence
APC1994-2013 = -2.2%, P < 0.05; mortality APC1994-2013 = -1.2%, P < 0.05). Trends
in Israeli Arabs remained stable. Significant incidence trend differences between
Ireland and Israeli Jews (P = 0.009) and between Israeli Jews and Arabs (P =
0.004) were observed. The only significant trend difference for mortality was
between Israeli Jews and Arabs (P = 0.038). Incidence-to-mortality ratios showed
stable trends in all groups except for Israeli Jews (APC1994-2013 = -1.0%, P <
0.05). CONCLUSIONS: Time trends in ovarian cancer incidence (decreasing) and
mortality (decreasing) were similar in Ireland, NI, and Israeli Jews, following
global trends, with a more prominent incidence decline in Israeli Jews.
Decreasing mortality trends are driven by falling incidence in the countries
studied rather than improved survival.
PMID- 28704324
TI - Fascin Is Associated With Aggressive Behavior and Poor Outcome in Uterine
Carcinosarcoma.
AB - OBJECTIVE: The mechanisms underlying the histogenesis and aggressiveness of
uterine carcinosarcoma (UCS) are poorly understood; however, previous studies
implicate epithelial-mesenchymal transition (EMT). Fascin is a proinvasive, actin
bundling protein and an important component of EMT. It is associated with poor
outcomes in human carcinoma, especially in estrogen receptor (ER)-negative tumors
arising in organs normally expressing ER. We sought to evaluate fascin expression
in UCS and its relationship to ER status, clinicopathologic indicators of tumor
aggressiveness, and survival outcomes. METHOD: Forty-four surgically staged cases
of UCS were immunohistochemically evaluated for fascin and estrogen receptor
alpha expression and correlated with clinicopathologic parameters derived from
electronic medical records and pathology reports. RESULTS: Fascin was only
expressed in malignant epithelium and mesenchyma and was uniformly absent in
background benign counterparts. Increased expression was associated with
extrapelvic disease (P = 0.028), higher stage (P = 0.021), larger tumor size (P =
0.032), shorter progression-free interval (P = 0.035), and reduced estrogen
receptor-alpha expression (P = 0.04). CONCLUSION: Fascin is aberrantly expressed
in both elements of UCS and is associated with aggressive behavior and worse
outcome. As a component of EMT and mediator of invasion, fascin may serve as a
target in future therapies.
PMID- 28704325
TI - Clinical Utility of Preoperative Computed Tomography in Patients With Endometrial
Cancer.
AB - OBJECTIVE: The aim of this study was to determine the clinical utility of routine
preoperative pelvic and abdominal computed tomography (CT) examinations in
patients with endometrial cancer (EC). METHODS: We retrospectively reviewed
records from patients with EC who underwent a preoperative endometrial biopsy and
had surgery at our institution from January 1999 through December 2008. In the
subset with an abdominal CT scan obtained within 3 months before surgery, we
evaluated the clinical utility of the CT scan. RESULTS: Overall, 224 patients
(18%) had a preoperative endometrial biopsy and an available CT scan. Gross intra
abdominal disease was observed in 10% and 20% of patients with preoperative
diagnosis of endometrioid G3 and type II EC, respectively, whereas less than 5%
of patients had a preoperative diagnosis of hyperplasia or low-grade EC. When
examining retroperitoneal findings, we observed that a negative CT scan of the
pelvis did not exclude the presence of pelvic node metastasis. Alternately, a
negative CT scan in the para-aortic area generally reduced the probability of
finding para-aortic dissemination but with an overall low sensitivity (42%).
However, the sensitivity for para-aortic dissemination was as high as 67% in
patients with G3 endometrioid cancer. In the case of negative para-aortic nodes
in the CT scan, the risk of para-aortic node metastases decreased from 18.8% to
7.5% in patients with endometrioid G3 EC. Up to 15% of patients with endometrioid
G3 cancer had clinically relevant incidental findings that necessitated medical
or surgical intervention. CONCLUSIONS: In patients with endometrioid G3 and type
II EC diagnosed by the preoperative biopsy, CT scans may help guide the operative
plan by facilitating preoperative identification of gross intra-abdominal disease
and enlarged positive para-aortic nodes that are not detectable during physical
examinations. In addition, CT may reveal other clinically relevant incidental
findings.
PMID- 28704326
TI - Single Marital Status and Infectious Mortality in Women With Cervical Cancer in
the United States.
AB - OBJECTIVE: Unmarried status including single marital status is associated with
increased mortality in women bearing malignancy. Infectious disease weights a
significant proportion of mortality in patients with malignancy. Here, we
examined an association of single marital status and infectious mortality in
cervical cancer. METHODS: This is a retrospective observational study examining
86,555 women with invasive cervical cancer identified in the Surveillance,
Epidemiology, and End Results Program between 1973 and 2013. Characteristics of
18,324 single women were compared with 38,713 married women in multivariable
binary logistic regression models. Propensity score matching was performed to
examine cumulative risk of all-cause and infectious mortality between the 2
groups. RESULTS: Single marital status was significantly associated with young
age, black/Hispanic ethnicity, Western US residents, uninsured status, high-grade
tumor, squamous histology, and advanced-stage disease on multivariable analysis
(all, P < 0.05). In a prematched model, single marital status was significantly
associated with increased cumulative risk of all-cause mortality (5-year rate:
32.9% vs 29.7%, P < 0.001) and infectious mortality (0.5% vs 0.3%, P < 0.001)
compared with the married status. After propensity score matching, single marital
status remained an independent prognostic factor for increased cumulative risk of
all-cause mortality (adjusted hazards ratio [HR], 1.15; 95% confidence interval
[CI], 1.11-1.20; P < 0.001) and those of infectious mortality on multivariable
analysis (adjusted HR, 1.71; 95% CI, 1.27-2.32; P < 0.001). In a sensitivity
analysis for stage I disease, single marital status remained significantly
increased risk of infectious mortality after propensity score matching (adjusted
HR, 2.24; 95% CI, 1.34-3.73; P = 0.002). CONCLUSIONS: Single marital status was
associated with increased infectious mortality in women with invasive cervical
cancer.
PMID- 28704327
TI - Examining the Effects of Time to Diagnosis, Income, Symptoms, and Incidental
Detection on Overall Survival in Epithelial Ovarian Cancer: Manitoba Ovarian
Cancer Outcomes (MOCO) Study Group.
AB - OBJECTIVE: The primary objectives of this study were to analyze data on time to
diagnosis and correlate this with overall survival. We secondarily analyzed the
effects of emergency room visits, symptoms, incidental findings, residence,
socioeconomic status, and residual disease on overall survival. METHODS: This
retrospective population-based descriptive cohort study examined all invasive
ovarian cancer cases in Manitoba, Canada, between 2004 and 2010.
Clinicopathologic, socioeconomic, and outcome data were collected. Analysis was
performed with Cox and logistic regression stratified by early and late stage.
RESULTS: Six hundred eighty-seven ovarian cancer patients were identified, with a
final cohort of 601 patients: 210 with early-stage (1/2) and 391 with late-stage
(3/4) disease. No presenting symptoms were associated with survival outcome.
Poorer survival was associated with increasing age (P = 0.0016) and neoadjuvant
chemotherapy (P = 0.0037). Higher income within the urban setting was also
associated with a survival advantage (P = 0.0037), whereas initial presentation
to the emergency room (P = 0.0399) was associated with decreased survival.
Finally, for advanced-stage disease, incidental diagnosis had a significantly
improved overall survival (hazard ratio, 0.424; 95% confidence interval, 0.27
0.67; P = 0.0003), even when accounting for confounding factors. Time from first
presentation to diagnosis was associated with survival (P = 0.0309). CONCLUSIONS:
This study found that time to diagnosis did not negatively impact overall
survival, although there was an association. Age, morphology, treatment type,
residual disease, medical comorbidities, and income were significant prognostic
factors. This is the first study to show a survival advantage to incidentally
finding an ovarian cancer. Further research is needed on the outcomes of pelvic
examination.
PMID- 28704328
TI - Randomized, Controlled Trial of Dexamethasone Versus Dexamethasone Plus
Hydrocortisone as Prophylaxis for Hypersensitivity Reactions Due to Paclitaxel
Treatment for Gynecologic Cancer.
AB - OBJECTIVE: The aim of this study was to assess intravenous hydrocortisone (HCT)
added to standard dexamethasone (DXM) prophylaxis for paclitaxel-associated
hypersensitivity reactions (HSRs). METHODS: Paclitaxel naives scheduled for 6
cycles of paclitaxel (plus platinum) were randomized to DXM alone (20 mg
intravenously [IV]) versus DXM plus HCT (100 mg IV) as premedication including
chlorpheniramine (10 mg IV), diphenhydramine (25 mg orally), and ranitidine (50
mg IV) 30 minutes before infusion. Clinic nurses observed for HSRs. Groups were
well balanced for cancer type, stage, drug allergy, chemotherapy naivete, mean
age, body mass index, and paclitaxel dose. RESULTS: The 44 DXM controls underwent
213 cycles and the 42 investigational DXM plus HCT group 192 per protocol cycles.
Hypersensitivity reactions were observed among 9 (4.2%) DXM only cycles compared
with 1 (0.5%) among DXM plus HCT cycles (P = 0.022). Hypersensitivity reactions
occurred in 8 (18%) DXM only patients and in 1 (2.4%) among those correctly
receiving DXM plus HCT (P = 0.030). All HSRs occurred in cycles 1 to 3, within 10
to 40 minutes after infusion initiation, and peaked in cycle 2 (5/39) for DXM
recipients and in cycle 3 (1/30) for DXM plus HCT. Hypersensitivity reaction
severity was grade 1 in 3 DXM only recipients and grade 2 in 6 DXM and 1 DXM plus
HCT. A sole grade 3 HSR was in an intention-to-treat DXM-HCT patient, who
erroneously received no HCT. Hypersensitivity reaction symptoms were facial
flushing (8 episodes), dyspnea (7), palmar rash (1), and transient hypotension
(1). Paclitaxel infusion was suspended for treatment of HSRs; in all cases,
symptoms mitigated and infusion successfully restarted for the remaining dose.
CONCLUSIONS: Adding HCT to routine DXM prophylaxis significantly decreased
paclitaxel HSR frequency.
PMID- 28704329
TI - Long-Term Oncological Outcome After Conventional Radical Hysterectomy Versus 2
Nerve-Sparing Modalities for Early Stage Cervical Cancer.
AB - OBJECTIVES: Nerve-sparing radical hysterectomy for early stage cervical cancer
was introduced to improve quality of life after treatment. Sparing the pelvic
autonomic nerves reduces bladder, bowel, and sexual dysfunction. The Leiden nerve
sparing radical hysterectomy (LNSRH) was modified to the Swift procedure, the
latter being more radical regarding the sacrouterine and parametrial resection.
We investigate whether nerve-sparing surgery has comparable oncological outcomes
as the conventional radical hysterectomy (CRH). Concurrently, we investigate
whether there is a difference regarding the oncological outcomes of the 2 nerve
sparing techniques. METHODS: This is a single-center, observational prospective
cohort study analyzing oncological outcomes in women undergoing CRH (1994-1999),
LNSRH (2001-2005), or Swift procedure (2006-2010) for early stage cervical cancer
(International Federation of Gynecology and Obstetrics IA2-IIA). RESULTS: Three
hundred sixty-three patients (124 CRH, 122 LNSRH, and 117 Swift) were included.
International Federation of Gynecology and Obstetrics stage IB2 or higher (P =
0.005) was significantly more prevalent in the CRH cohort. The 5-year pelvic
relapse-free survival and overall survival were not significantly different
between the 3 cohorts (P = 0.116). Regarding the nerve-sparing cohorts, the Swift
cohort showed a significant better 5-year overall survival (87.2%) compared with
the LNSRH cohort (78.8%) (P = 0.04). In the LNSRH cohort, resection planes less
than 5 mm free and need for adjuvant therapy were significantly higher than in
the Swift cohort (P = 0.026 and 0.046, respectively). CONCLUSIONS: The nerve
sparing radical hysterectomy shows a similar oncological outcome compared with
the CRH. The more radical Swift version of nerve-sparing techniques is preferable
to the former LNSRH procedure.
PMID- 28704330
TI - Images in Anesthesiology: Proper Positioning of an Impella 2.5 and CP Heart Pump.
PMID- 28704331
TI - MIS Single-position Lateral and Oblique Lateral Lumbar Interbody Fusion and
Bilateral Pedicle Screw Fixation: Feasibility and Perioperative Results.
AB - STUDY DESIGN: Retrospective review of prospectively collected data of the first
72 consecutive patients treated with single-position one- or two-level lateral
(LLIF) or oblique lateral interbody fusion (OLLIF) with bilateral percutaneous
pedicle screw and rod fixation by a single spine surgeon. OBJECTIVE: To evaluate
the clinical feasibility, accuracy, and efficiency of a single-position technique
for LLIF and OLLIF with bilateral pedicle screw and rod fixation. SUMMARY OF
BACKGROUND DATA: Minimally-invasive lateral interbody approaches are performed in
the lateral decubitus position. Subsequent repositioning prone for bilateral
pedicle screw and rod fixation requires significant time and resources and does
not facilitate increased lumbar lordosis. METHODS: The first 72 consecutive
patients (300 screws) treated with single-position LLIF or OLLIF and bilateral
pedicle screws by a single surgeon between December 2013 and August 2016 were
included in the study. Screw accuracy and fusion were graded using computed
tomography and several timing parameters were recorded including retractor,
fluoroscopy, and screw placement time. Complications including reoperation,
infection, and postoperative radicular pain and weakness were recorded. RESULTS:
Average screw placement time was 5.9 min/screw (standard deviation, SD: 1.5 min;
range: 3-9.5 min). Average total operative time (interbody cage and pedicle screw
placement) was 87.9 minutes (SD: 25.1 min; range: 49-195 min). Average
fluoroscopy time was 15.0 s/screw (SD: 4.7 s; range: 6-25 s). The pedicle screw
breach rate was 5.1% with 10/13 breaches measured as < 2 mm in magnitude. Fusion
rate at 6-months postoperative was 87.5%. Two (2.8%) patients underwent
reoperation for malpositioned pedicle screws with subsequent resolution of
symptoms. CONCLUSION: The single-position, all-lateral technique was found to be
feasible with accuracy, fluoroscopy usage, and complication rates comparable with
the published literature. This technique eliminates the time and staffing
associated with intraoperative repositioning and may lead to significant
improvements in operative efficiency and cost savings. LEVEL OF EVIDENCE: 4.
PMID- 28704332
TI - Image Diagnostic Classification of Magnetic Resonance T2 Increased Signal
Intensity in Cervical Spondylotic Myelopathy: Clinical Evaluation Using
Quantitative and Objective Assessment.
AB - STUDY DESIGN: A prospective imaging study. OBJECTIVE: The study investigated
whether the classification of increased signal intensity (ISI) using magnetic
resonance imaging (MRI) reflects the severity of symptoms in patients with
cervical spondylotic myelopathy (CSM). SUMMARY OF BACKGROUND DATA: Although the
ISI on MRI in patients with CSM is observed, the degree of ISI has not been
examined. The association between ISI and the surgical outcomes in cervical
myelopathy remains controversial. METHODS: A total of 505 consecutive patients
with CSM (311 males; 194 females) were enrolled. The mean age was 66.6 years
(range, 41-91 yrs), with an average postoperative follow-up period of 26.5 +/-
12.5 months. The ISI was classified into three groups based on sagittal T2
weighted MRI as follows: Grade 0, none; Grade 1, light (obscure); and Grade 2,
intense (bright). Pre- and postoperative neurological status was evaluated using
the Japanese Orthopedic Association scoring system for cervical myelopathy (JOA
score) and quantifiable tests, including the 10-s grip and release test (10-s G&R
test) and the 10-s step test. RESULTS: The preoperative MRI showed 168 patients
in Grade 0, 169 patients in Grade 1, and 168 in Grade 2, with no age differences
among three groups. Grade 2 patients had a longer duration of symptom compared
with the other grades. Grade 0 patients had a better postoperative JOA score and
recovery rate compared with the other grades. The preoperative and postoperative
scores in the G&R test and steps were better in the Grade 0 patients compared
with the other grades. Grade 1 and 2 patients had similar outcomes and recovery
rates. CONCLUSION: ISI on MRI in patients with CSM was prospectively classified
into three grades. The ISI grading was not associated with the preoperative
severity of myelopathy and outcomes. LEVEL OF EVIDENCE: 2.
PMID- 28704333
TI - Impact of Depression on Patient-Reported Outcome Measures After Lumbar Spine
Decompression.
AB - STUDY DESIGN: A retrospective cohort study. OBJECTIVE: The aim of this study was
to investigate the effect depression has on the improvement of patient-reported
outcome measures (PROMs) following lumbar decompression. SUMMARY OF BACKGROUND
DATA: Decompression without fusion is a viable treatment option for lumbar spine
stenosis. Depression reportedly has a negative impact on PROMs after certain
types of spine surgery, though verification of this with new, more precise
outcome measures is needed. METHODS: We included consecutive adult patients who
underwent lumbar decompression for lumbar spine stenosis between 2016 and 2017
who had PROM information system (PROMIS) physical function, pain, depression, and
Oswestry Disability Index (ODI) questionnaires completed preoperatively and at 6
month follow-up. Patients with a PROMIS depression score >50 or <50 were
allocated to the depressed and not depressed groups, respectively. The cohorts
were compared using unpaired t tests and repeated-measures two-way analysis of
variance (ANOVA) with statistical significance taken at P < 0.05. RESULTS: The
analysis included 55 patients without depression and 56 patients with depression.
Depressed patients had worse preoperative PROMIS physical function (30.08 vs.
36.66, P = 0.005), PROMIS pain (69.36 vs. 64.69, P < 0.0001), and ODI scores
(51.92 vs. 36.35, P < 0.0001). Similarly, the depressed group had worse
postoperative PROMIS physical function (36.29 vs. 40.34, P = 0.005), PROMIS pain
(60.16 vs. 54.87, P < 0.0001), and ODI scores (37.01 vs. 23.44, P = 0.0003). We
observed a statistically significant interaction between depression status and
pre to postoperative improvement in outcome for PROMIS physical function
(F[1,109] = 102.5, P < 0.0001) and depression scores (F[1,109] = 15.38, P =
0.0002). No interaction was found for pain and ODI scores. CONCLUSION: Our
results suggest that depressed patients experience a greater magnitude of
improvement in PROMIS physical function and depression scores than nondepressed
patients. Despite this, depressed patients have worse postoperative outcomes for
PROMIS physical function, depression, pain, and ODI. These findings are important
for risk stratifying and treating depressed patients before lumbar spine
decompression. LEVEL OF EVIDENCE: 3.
PMID- 28704335
TI - Mesenchymal Stromal Cell Therapy for Solid Organ Transplantation.
AB - Improvement of long-term outcome of kidney transplantation has reached its limits
due to consequences of efficient, but nonspecific immunosuppressive drugs.
Mesenchymal stromal cells (MSC) have been proposed as an alternative strategy for
more refined therapy. The interest in MSCs comes from their anti-inflammatory
properties on the one hand and their propensity to ameliorate tissue damage and
mediate repair on the other hand. First clinical trials have demonstrated that
administration of MSCs in kidney transplant recipients is safe and feasible, and
follow-up studies have been initiated with the desired clinical efficacy to
reduce ischemia-reperfusion injury, to prevent/reverse acute transplant
rejection, and to improve long-term transplant survival with minimization of
immunosuppression. To further promote wider application of MSC in renal
transplantation, it is of importance to determine efficacy, to increase the
understanding of the mechanism of action, and to develop tools to identify
eligible patients. In addition, we should overcome challenges particularly at the
transition of early phase I studies to more advanced stages of clinical
development. In this review, latest insights, first clinical experiences, and
future challenges of MSC in solid organ transplantation are discussed.
PMID- 28704336
TI - Plasmatic Villin 1 Is a Novel In Vivo Marker of Proximal Tubular Cell Injury
During Renal Ischemia-Reperfusion.
AB - BACKGROUND: Early detection of acute kidney injury (AKI), a common condition with
a high mortality risk, can be facilitated by specific and reliable biomarkers.
Villin 1, a protein typically found in the brush borders of proximal tubular
cells, has been detected in urine of patients with AKI, but its possible release
in plasma remains unexplored. METHODS: We measured the presence of villin 1 by
immunohistochemistry on kidney sections and by Western blotting in plasma samples
from rats subjected to renal ischemia-reperfusion injury, pigs subjected to renal
transplantation and liver transplantation patients that developed AKI. Moreover,
rats were treated with necrostatin-1, an inhibitor of programmed necrosis
(necroptosis), which occurs in renal tubular cells during AKI. Villin 1 levels
were compared with other renal injury markers (creatinine, aspartate
transaminase, and heart-type fatty acid binding protein). RESULTS: During AKI,
plasmatic villin 1 levels corresponded with the severity of kidney injury and
dysfunction. Its detection in plasma was associated with a redistribution in the
kidney tissue. Unlike the levels of other markers, plasmatic villin 1 decreased
already after a short (3 hours) treatment with necrostatin-1 during renal
ischemia-reperfusion injury. The presence of plasmatic villin 1 was confirmed in
patients who experienced AKI after liver transplantation. CONCLUSIONS: Villin 1
is released in plasma during AKI and shows potential as an early marker for
proximal tubular injury/necrosis and warrants further investigation.
PMID- 28704337
TI - Alleviation of Ischemia-Reperfusion Injury in Liver Steatosis by Augmenter of
Liver Regeneration Is Attributed to Antioxidation and Preservation of
Mitochondria.
AB - BACKGROUND: Fatty liver is one of the major impediments to liver surgery and
liver transplantation because steatotic hepatocytes are more susceptible to
ischemia-reperfusion injury (IRI). In this study, the effects of augmenter of
liver regeneration (ALR) on hepatic IRI in steatotic mice were investigated.
METHODS: In vivo, liver steatosis of mice was induced by feeding a methionine
choline-deficient diet for 2 weeks. Three days before hepatic partial warm IRI,
mice were transfected with the ALR-containing adenovirus. In an in vitro study,
the protective effect of ALR on steatotic HepG2 cells was analyzed after
hypoxia/reoxygenation (HR) treatment. RESULTS: The transfection of the ALR gene
into steatotic mice attenuated liver injury, inhibiting hepatic oxidative stress,
increasing antioxidation capacities, promoting liver regeneration, and
consequently suppressing cell apoptosis/death. Furthermore, resistance to HR
injury was notably increased in ALR-transfected cells compared with the vector
transfected cells. The HR-induced rise in the mitochondrial reactive oxygen
species was reduced, and cellular antioxidant activities were enhanced. The ALR
transfection prevented cells from apoptosis, which can be attributed to the
preservation of the mitochondrial membrane potential, enhancement of oxygen
consumption rate and production of adenosine triphosphate. CONCLUSIONS: ALR
protects steatotic hepatocytes from IRI by attenuating oxidative stress and
mitochondrial dysfunction, as well as improving antioxidant effect. ALR may be
used as a potential therapeutic agent when performing surgery and transplantation
of steatotic liver.
PMID- 28704338
TI - Analysis of metastatic involvement in bone using anatomical and functional
information from 18F-FDG PET/CT.
AB - PURPOSE: Although the overall incidence of bone metastasis is not known, over one
half of the people who die of cancer in the USA every year are thought to have
bone involvement. In this study we have developed a method to quantify the
metabolic and anatomic changes induced by different types of bone metastases in
cancer patients using PET/CT images. PATIENTS AND MATERIALS: Seventy-three cancer
patients with no previous history of chemotherapy or radiotherapy who had
definite bone metastases documented by PET/CT and other conventional modalities
were selected for this study. PET and computed tomography (CT) images were
resampled to the same pixel size. Thereafter, the bone structure was segmented
using thresholding. The 50% of the maximum standardized uptake value within the
bone mask was used to identify bone lesions in each slice. Using the final
regions of interest defined at 70% of the maximum, the lesion characteristics
including the mean Hounsfield Units were computed from the PET/CT images. The
lesions were subjected to visual confirmation by an experienced physician who
also categorized them on the basis of the appearances in CT as lytic, sclerotic,
mixed, or no-change type. The lesion characteristics were compared using
statistical methods. RESULTS: In all, 340 bony lesions in 73 patients with
different cancer types were analyzed. The lesions were further categorized into
four groups on the basis of their anatomical location. The spine hosts the
largest number of lesions. The lumbar bones are the most preferential sites
within the spine. Statistical comparison of CT values indicated that the
difference between no-change and lytic types was significant. Uptake period did
not seem to have a significant impact on no-change and sclerotic types.
Quantitatively, maximum standardized uptake value for lytic, no change, mixed,
and sclerotic lesions were 7.4, 6.1, 8.2, and 7.2, respectively. CONCLUSION: A
quantitative method provides a convenient way that may serve as a useful tool in
monitoring and assessing the response to therapy.
PMID- 28704339
TI - Quantitative analysis of normal and pathologic adrenal glands with 18F-FDOPA
PET/CT: focus on pheochromocytomas.
AB - INTRODUCTION: Many studies have reported the high performance of 6-fluorine-18
fluorodihydroxyphenilalanine (F-FDOPA) PET/CT in the diagnosis of
pheochromocytomas but nobody seems to have investigated physiological and
pathological adrenal glands from a quantitative point of view. The purpose of the
present study was to assess the quantitative F-FDOPA uptake of normal and
pathologic adrenal glands and to establish thresholds to characterize
pheochromocytomas. We were especially interested in characterizing the remaining
adrenal glands captation after an adrenalectomy. PATIENTS AND METHODS: We
reviewed 112 F-FDOPA PET/CT scans taken for different indications. A total of 212
adrenal glands, of which 17 were pheochromocytomas, were analyzed on the basis of
their functional and morphological features. The final diagnosis was based on
histologic proof when available (six pheochromocytomas) or after synthesis of
clinical, biological, morphological, and functional results. Maximum standardized
uptake value (SUVmax), mediastinum, and liver ratios in case of
pheochromocytomas, adenomas, and solitary adrenal glands were determined and
compared with those of healthy glands. Receiver operating characteristic curves
were determined and areas under the curve were compared for different cutoffs of
each index. RESULTS: Pheochromocytomas demonstrated a higher F-FDOPA uptake
compared with normal adrenal glands (mean SUVmax: 7.5, SD 4.0, range: 3.5-20.0
vs. mean SUVmax: 2.6, SD: 0.8, range: 1.0-6.9) (P<0.0001). An SUVmax threshold of
4.2 has a sensitivity and specificity of 94 and 98%, respectively. The areas
under the curve were 0.988, 0.991, and 0.987 for an SUVmax of 4.2, a mediastinum
ratio of 3.0, and a liver ratio of 1.7, respectively. A large number of
nonsecreting pheochromocytomas were noticed. On the basis of the SUVmax no
statistically significant difference was found between secreting (SUVmax: 8.9,
SD: 5.3) and nonsecreting pheochromocytomas (SUVmax: 5.1, SD: 0.9) (P=0.141).
After unilateral adrenalectomy, solitary glands presented no increased uptake
compared with healthy adrenal glands. An unexpected lower captation was also
observed (SUVmax: 2.0, P=0.047). CONCLUSION: We confirm the high affinity of F
FDOPA for secreting or nonsecreting pheochromocytoma. Indeed within a series of
various adrenal glands, only these tumors presented a significant increased
uptake compared with normal adrenal glands. Because of a high rate of
nonhypersecreting lesions, F-FDOPA can act as a surrogate to biological assays.
After an adrenalectomy, the remaining glands did not demonstrate compensatory
accumulation of F-FDOPA. To our knowledge this last point has never been
addressed.
PMID- 28704340
TI - Uptake in the pancreatic uncinate process on the 111In-octreotide scintigraphy:
How to distinguish physiological from pathological uptake?
AB - BACKGROUND: The aim of this study was to assess the relevance of physiological In
octreotide uptake in the head of pancreas and to establish its imaging features
in comparison with pathological uptake in patients with neuroendocrine tumors
(NET). PATIENTS AND METHODS: We retrospectively reviewed all patients that
underwent In-octreotide single-photon emission tomography (SPECT) scintigraphy in
our institution. Only patients with an isolated uptake in the head of the
pancreas were included. In-octreotidescintigraphy consisted in planar whole-body
and abdominal SPECT/computed tomography (CT) images acquired at 6 and 30 h'
postinjection. Different imaging features of the pancreatic focalized uptake were
assessed: its precise location on the pancreas head, shape, intensity [visually
and quantitatively by calculating the pancreatic to hepatic uptake ratio (L/H
ratio)] and intensity changes. RESULTS: Thirteen patients out of 230 were
included. Among them, a pancreatic NET was confirmed in five patients. On In
octreotide SPECT/CT, two of these had uptake located in the uncinate process, and
three had uptake focused in the right lateral borders or in the whole head. SPECT
images demonstrated high uptake (L/H ratio >2) in four patients out of five. In
the eight remaining patients, pancreatic NET was ruled out. For all of these
physiological cases, SPECT/CT acquisitions revealed that the uptake was both
located in the uncinate process and with an L/H ratio below 2. CONCLUSION: The
simple criteria of localization and uptake quantification can help to
discriminate between a possible physiological uptake in the uncinate process of
the pancreatic head and a pathological uptake induced by a NET.
PMID- 28704341
TI - Uptake of the prostate-specific membrane antigen-targeted PET radiotracer 18F
DCFPyL in elastofibroma dorsi.
AB - OBJECTIVE: PET imaging using radiotracers that target prostate-specific membrane
antigen (PSMA) are increasingly being used in the evaluation of men with prostate
cancer (PCa). It is therefore of increasing importance for imaging specialists to
recognize potential pitfalls of this novel imaging technique. In this report, we
describe a series of benign elastofibroma dorsi with uptake of the PSMA-targeted
PET radiotracer F-DCFPyL. PATIENTS AND METHODS: We retrospectively analyzed the
imaging data of 75 men with PCa who were consecutively imaged with F-DCFPyL
PET/CT. Acquired images were reviewed for the presence of radiotracer uptake in
the region of the scapular tip adjacent to the chest wall. Only those lesions
with discrete radiotracer uptake corresponding to an area on CT with the
characteristic appearance of an elastofibroma were considered positive. RESULTS:
In total, 18/75 (24.0%) patients had evidence of at least one elastofibroma dorsi
on F-DCFPyL PET/CT. Eight (44.4%) of these patients had unilateral lesions, all
of which were right sided. Detected lesions had a median maximal diameter of 2.3
cm (range: 1.3-8.4 cm) and a median perpendicular thickness to the chest wall of
0.9 cm (range: 0.6-2.5 cm). The median maximum standardized uptake value of
detected lesions was 1.4 (range: 1.1-2.4) and the median maximum standardized
uptake value corrected to lean body mass was 1.1 (range: 0.8-1.7). CONCLUSION:
This study is the first to report uptake of a PSMA-targeted PET radiotracer in
elastofibroma dorsi. Radiotracer uptake in these benign lesions should not be
falsely mistaken as sites of metastatic PCa.
PMID- 28704342
TI - A novel compact small field of view hybrid gamma camera: first clinical results.
AB - INTRODUCTION: Hybrid imaging has proven to be a major innovation in nuclear
medicine, allowing the fusion of functional information with anatomical detail.
In the past, the use of hybrid imaging such as PET-CT, PET-MRI and SPECT-CT has
been of great clinical benefit; however, these scanners are relatively large and
bulky. We have developed and investigated the clinical application of a compact
small field of view hybrid gamma camera (HGC) that is suitable for small-organ
imaging at the patient bedside. PATIENTS AND METHODS: The HGC - consisting of a
CsI(Tl) scintillation crystal coupled to an electron-multiplying charge-coupled
device and an optical camera - was used in this study. Eligible patients
attending the nuclear medicine clinic at Queen's Medical Centre, Nottingham
University Hospitals NHS Trust, Nottingham, UK, were invited to take part in this
study. Following the standard injection of either a Tc-labelled or I-labelled
radiopharmaceutical, images of the patient were acquired using the HGC and
presented in a fused optical-gamma display. RESULTS: There were 24 patients
enrolled in the study (age range between 30 and 83 years, mean: 58.6 years),
images of 18 of whom were successfully acquired. These included patients who were
undergoing bone, thyroid, lacrimal drainage, DaTscan and lymphatic imaging. In
general, the small field of view system was well suited to small-organ imaging.
The uptake could be clearly seen in relation to the patient surface anatomy and
showed particular promise for lymphatic, thyroid and lacrimal drainage studies.
CONCLUSION: This pilot study has demonstrated the first clinical results of
hybrid optical-gamma imaging in patients. The use of this system has raised new
possibilities for small-organ imaging, in which the localization of
radiopharmaceutical uptake can be presented in an anatomical context using
optical imaging. The compact nature of the hybrid system offers the potential for
bedside investigations and intraoperative use.
PMID- 28704343
TI - Pilot Trial of a Home-based Physical Activity Program for African American Women.
AB - PURPOSE: This study aimed to assess the feasibility of a Home-based, Individually
tailored Physical activity Print (HIPP) intervention for African American women
in the Deep South. METHODS: A pilot randomized trial of the HIPP intervention (N
= 43) versus wellness contact control (N = 41) was conducted. Recruitment,
retention, and adherence were examined, along with physical activity (7-d
physical activity recalls, accelerometers) and related psychosocial variables at
baseline and 6 months. RESULTS: The sample included 84 overweight/obese African
American women 50-69 yr old in Birmingham, AL. Retention was high at 6 months
(90%). Most participants reported being satisfied with the HIPP program and
finding it helpful (91.67%). There were no significant between-group differences
in physical activity (P = 0.22); however, HIPP participants reported larger
increases (mean of +73.9 min.wk (SD 90.9)) in moderate-intensity or greater
physical activity from baseline to 6 months compared with the control group
(+41.5 min.wk (64.4)). The HIPP group also reported significantly greater
improvements in physical activity goal setting (P = 0.02) and enjoyment (P =
0.04) from baseline to 6 months compared with the control group. There were no
other significant between-group differences (6-min walk test, weight, physical
activity planning, behavioral processes, stage of change); however, trends in the
data for cognitive processes, self-efficacy, outcome expectations, and family
support for physical activity indicated small improvements for HIPP participants
(P > 0.05) and declines for control participants. Significant decreases in
decisional balance (P = 0.01) and friend support (P = 0.03) from baseline to 6
months were observed in the control arm and not the intervention arm.
CONCLUSIONS: The HIPP intervention has great potential as a low-cost, high-reach
method for reducing physical activity-related health disparities. The lack of
improvement in some domains may indicate that additional resources are needed to
help this target population reach national guidelines.
PMID- 28704344
TI - Effects of Altering Trunk Position during Landings on Patellar Tendon Force and
Pain.
AB - PURPOSE: This study aimed to verify the immediate effects of altering sagittal
plane trunk position during jump landings on lower limb biomechanics, patellar
tendon force, and pain of athletes with and without patellar tendinopathy.
METHODS: Twenty-one elite male athletes were categorized into three groups:
athletes with patellar tendinopathy (TG; n = 7), asymptomatic athletes with
patellar tendon abnormalities (n = 7), and asymptomatic athletes without tendon
abnormalities (CG; n = 7). A biomechanical evaluation was conducted while the
athletes performed drop landings from a bench in a self-selected trunk position
(SS). Afterward, the athletes were randomly assigned to land with either a flexed
trunk position (FLX) or an extended trunk position (EXT). Variables of interest
for this study included sagittal plane peak kinematics, kinetics, patellar tendon
force, and pain during the landing tasks. RESULTS: Peak patellar tendon force,
knee extensor moment, and knee pain decreased in the FLX landing compared with
the SS landing, regardless of group. In addition, peak patellar tendon force,
knee extensor moment, and vertical ground reaction force were smaller in the FLX
landing compared with the EXT landing. The TG had smaller peak ankle dorsiflexion
compared with the CG during jump landings, regardless of trunk position.
CONCLUSIONS: Landing with greater trunk flexion decreased patellar tendon force
in elite jumping athletes. An immediate decrease in knee pain was also observed
in symptomatic athletes with a more flexed trunk position during landing.
Increasing trunk flexion during landing might be an important strategy to reduce
tendon overload in jumping athletes.
PMID- 28704345
TI - The Effects and Possible Mechanisms of Puerarin to Treat Uterine Fibrosis Induced
by Ischemia-Reperfusion Injury in Rats.
AB - BACKGROUND Tissues fibrosis is caused by ischemia-reperfusion injury (IRI) and
results in organ dysfunction. In this study, we aimed to investigate whether
fibrosis occurs after uterine ischemia-reperfusion injury, and to investigate the
effects of puerarin (Pur) on the fibrosis process in rats. MATERIAL AND METHODS
Twenty-four female Wistar rats were randomly divided into three groups (8 in each
group): the control group rats only received operation without uterine ischemic,
the IRI group and the IRI + Pur group rats received 30-minutes ischemia and 2
weeks of reperfusion. Pur was orally administered at the onset of reperfusion.
Picrosirius red staining was used to assess uterine fibrosis.
Immunohistochemistry was used to detect the expression levels of transforming
growth factor (TGF)-beta and a-smooth muscle actin (alpha-SMA). Western blotting
was used to evaluate the expression of chymase, TGF-beta, alpha-SMA, and the
activity of the Wnt/beta-catenin pathway. RESULTS Uterine fibrosis in the IRI+Pur
group was significantly decreased compared with the IRI group. In addition,
immunohistochemistry reveals that TGF-beta and a-SMA were decreased in the
IRI+Pur group compared with the IRI group. Western blotting results showed that
Pur significantly suppresses the increase in chymase, alpha-SMA, TGF-beta, and b
catenin expression levels induced by IRI. CONCLUSIONS The results indicated that
IRI could induce uterine fibrosis and that Pur had an improvement effect on IRI
induced uterine fibrosis by downregulating the activity of mast cell chymase, TGF
beta, alpha-SMA, and the Wnt/beta-catenin pathway.
PMID- 28704346
TI - Mortality from Amyotrophic Lateral Sclerosis and Parkinson's Disease Among
Different Occupation Groups - United States, 1985-2011.
AB - Amyotrophic lateral sclerosis (ALS) and Parkinson's disease, both progressive
neurodegenerative diseases, affect >1 million Americans (1,2). Consistently
reported risk factors for ALS include increasing age, male sex, and cigarette
smoking (1); risk factors for Parkinson's disease include increasing age, male
sex, and pesticide exposure, whereas cigarette smoking and caffeine consumption
are inversely associated (2). Relative to cancer or respiratory diseases, the
role of occupation in neurologic diseases is much less studied and less well
understood (3). CDC evaluated associations between usual occupation and ALS and
Parkinson's disease mortality using data from CDC's National Institute for
Occupational Safety and Health (NIOSH) National Occupational Mortality
Surveillance (NOMS), a population-based surveillance system that includes
approximately 12.1 million deaths from 30 U.S. states.* Associations were
estimated using proportionate mortality ratios (PMRs), standardizing indirectly
by age, sex, race, and calendar year to the standard population of all NOMS
deaths with occupation information. Occupations associated with higher
socioeconomic status (SES) had elevated ALS and Parkinson's disease mortality.
The shifts in the U.S. workforce toward older ages and higher SES occupations?
highlight the importance of understanding this finding, which will require
studies with designs that provide evidence for causality, detailed exposure
assessment, and adjustment for additional potential confounders.
PMID- 28704347
TI - Pneumococcal Vaccination Among Medicare Beneficiaries Occurring After the
Advisory Committee on Immunization Practices Recommendation for Routine Use Of 13
Valent Pneumococcal Conjugate Vaccine and 23-Valent Pneumococcal Polysaccharide
Vaccine for Adults Aged >=65 Years.
AB - On September 19, 2014, CDC published the Advisory Committee on Immunization
Practices (ACIP) recommendation for the routine use of 13-valent pneumococcal
conjugate vaccine (PCV13) among adults aged >=65 years, to be used in series with
23-valent pneumococcal polysaccharide vaccine (PPSV23) (1). This replaced the
previous recommendation that adults aged >=65 years should be vaccinated with a
single dose of PPSV23. As a proxy for estimating PCV13 and PPSV23 vaccination
coverage among adults aged >=65 years before and after implementation of these
revised recommendations, CDC analyzed claims for vaccination submitted for
reimbursement to the Centers for Medicare & Medicaid Services (CMS). Claims from
any time during a beneficiary's enrollment in Medicare Parts A (hospital
insurance) and B (medical insurance) since reaching age 65 years were assessed
among beneficiaries continuously enrolled in Medicare Parts A and B during annual
periods from September 19, 2009, through September 18, 2016. By September 18,
2016, 43.2% of Medicare beneficiaries aged >=65 years had claims for at least 1
dose of PPSV23 (regardless of PCV13 status), 31.5% had claims for at least 1 dose
of PCV13 (regardless of PPSV23 status), and 18.3% had claims for at least 1 dose
each of PCV13 and PPSV23. Claims for either type of pneumococcal vaccine were
highest among beneficiaries who were older, white, or with chronic and
immunocompromising medical conditions than among healthy adults. Implementation
of the National Vaccine Advisory Committee's standards for adult immunization
practice to assess vaccination status at every patient encounter, recommend
needed vaccines, and administer vaccination or refer to a vaccinating provider
might help increase pneumococcal vaccination coverage and reduce the risk for
pneumonia and invasive pneumococcal disease among older adults (2).
PMID- 28704348
TI - QuickStats: Age-Adjusted* Alzheimer's Disease Death Rates? Among Persons Aged
>=65 Years, by StateS - United States, 2015.
AB - In 2015, the age-adjusted Alzheimer's disease death rate among persons aged >=65
years in the United States was 231.0 per 100,000 population. The five states with
the highest age-adjusted death rates for Alzheimer's disease were South Carolina
(362.8), Washington (349.6), Mississippi (346.5), Tennessee (340.8), and
Louisiana (333.6). New York had the lowest rate (99.0), followed by Maryland
(128.2), Alaska (131.7), Connecticut (149.3), and the District of Columbia
(152.2).
PMID- 28704349
TI - Announcement: Implementation of the Vaccine Adverse Event Reporting System 2.0
Reporting Form.
AB - The Vaccine Adverse Event Reporting System (VAERS), co-managed by CDC and the
Food and Drug Administration (FDA), is the national postmarketing safety
monitoring system that accepts reports about adverse events that occur after
administration of U.S.-licensed vaccines (1,2). On June 30, 2017, CDC and FDA
implemented a revised reporting form and a new process for submitting reports to
VAERS. Persons reporting adverse events are now able to use the VAERS 2.0 online
reporting tool to submit reports directly online; alternatively, they may
download and complete the writable and savable VAERS 2.0 form and submit it using
an electronic document upload feature.
PMID- 28704350
TI - Measles Outbreak - Minnesota April-May 2017.
AB - On April 10, 2017, the Minnesota Department of Health (MDH) was notified about a
suspected measles case. The patient was a hospitalized child aged 25 months who
was evaluated for fever and rash, with onset on April 8. The child had no history
of receipt of measles-mumps-rubella (MMR) vaccine and no travel history or known
exposure to measles. On April 11, MDH received a report of a second hospitalized,
unvaccinated child, aged 34 months, with an acute febrile rash illness with onset
on April 10. The second patient's sibling, aged 19 months, who had also not
received MMR vaccine, had similar symptoms, with rash onset on March 30. Real
time reverse transcription-polymerase chain reaction (rRT-PCR) testing of
nasopharyngeal swab or throat specimens performed at MDH confirmed measles in the
first two patients on April 11, and in the third patient on April 13; subsequent
genotyping identified genotype B3 virus in all three patients, who attended the
same child care center. MDH instituted outbreak investigation and response
activities in collaboration with local health departments, health care
facilities, child care facilities, and schools in affected settings. Because the
outbreak occurred in a community with low MMR vaccination coverage, measles
spread rapidly, resulting in thousands of exposures in child care centers,
schools, and health care facilities. By May 31, 2017, a total of 65 confirmed
measles cases had been reported to MDH (Figure 1); transmission is ongoing.
PMID- 28704351
TI - High Risk for Invasive Meningococcal Disease Among Patients Receiving Eculizumab
(Soliris) Despite Receipt of Meningococcal Vaccine.
AB - Use of eculizumab (Soliris, Alexion Pharmaceuticals), a terminal complement
inhibitor, is associated with a 1,000-fold to 2,000-fold increased incidence of
meningococcal disease (1). Administration of meningococcal vaccines is
recommended for patients receiving eculizumab before beginning treatment (2,3).
Sixteen cases of meningococcal disease were identified in eculizumab recipients
in the United States during 2008-2016; among these, 11 were caused by
nongroupable Neisseria meningitidis. Fourteen patients had documentation of
receipt of at least 1 dose of meningococcal vaccine before disease onset. Because
eculizumab recipients remain at risk for meningococcal disease even after receipt
of meningococcal vaccines, some health care providers in the United States as
well as public health agencies in other countries recommend antimicrobial
prophylaxis for the duration of eculizumab treatment; a lifelong course of
treatment is expected for many patients. Heightened awareness, early care
seeking, and rapid treatment of any symptoms consistent with meningococcal
disease are essential for all patients receiving eculizumab treatment, regardless
of meningococcal vaccination or antimicrobial prophylaxis status.
PMID- 28704352
TI - Racial and Geographic Differences in Breastfeeding - United States, 2011-2015.
AB - Breastfeeding provides numerous health benefits for infants and mothers alike.
The American Academy of Pediatrics recommends exclusive breastfeeding for
approximately the first 6 months of life and continued breastfeeding with
complementary foods through at least the first year (1). National estimates
indicate substantial differences between non-Hispanic black (black) and non
Hispanic white (white) infants across breastfeeding indicators in the United
States (2). CDC analyzed 2011-2015 National Immunization Survey (NIS) data for
children born during 2010-2013 to describe breastfeeding initiation, exclusivity
through 6 months and duration at 12 months among black and white infants. Among
the 34 states (including the District of Columbia [DC]) with sufficient sample
size (>=50 per group), initiation rates were significantly (p<0.05) lower among
black infants than white infants in 23 states; in 14 of these states (primarily
in the South and Midwest), the difference was at least 15 percentage points. A
significant difference of at least 10 percentage points was identified in
exclusive breastfeeding through 6 months in 12 states and in breastfeeding at 12
months in 22 states. Despite overall increases in breastfeeding rates for black
and white infants over the last decade, racial disparities persist. Interventions
specifically addressing barriers to breastfeeding for black women are needed.
PMID- 28704353
TI - Organization and function of the 3D genome.
PMID- 28704354
TI - Structural plasticity and reorganisation in chronic pain.
PMID- 28704355
TI - A new view into prokaryotic cell biology from electron cryotomography.
PMID- 28704356
TI - Gap junctions and cancer: communicating for 50 years.
PMID- 28704357
TI - That gut feeling.
PMID- 28704358
TI - Obesity promotes prostate cancer invasion.
PMID- 28704359
TI - From Krebs to clinic: glutamine metabolism to cancer therapy.
PMID- 28704361
TI - From Krebs to clinic: glutamine metabolism to cancer therapy.
PMID- 28704362
TI - Local and global genetic diversity of protozoan parasites: Spatial distribution
of Cryptosporidium and Giardia genotypes.
AB - Cryptosporidiosis and giardiasis are recognized as significant enteric diseases
due to their long-term health effects in humans and their economic impact in
agriculture and medical care. Molecular analysis is essential to identify species
and genotypes causing these infectious diseases and provides a potential tool for
monitoring. This study uses information on species and genetic variants to gain
insights into the geographical distribution and spatial patterns of
Cryptosporidium and Giardia parasites. Here, we describe the population
heterogeneity of genotypic groups within Cryptosporidium and Giardia present in
New Zealand using gp60 and gdh markers to compare the observed variation with
other countries around the globe. Four species of Cryptosporidium (C. hominis, C.
parvum, C. cuniculus and C. erinacei) and one species of Giardia (G.
intestinalis) were identified. These species have been reported worldwide and
there are not unique Cryptosporidium gp60 subtype families and Giardia gdh
assemblages in New Zealand, most likely due to high gene flow of historical and
current human activity (travel and trade) and persistence of large host
population sizes. The global analysis revealed that genetic variants of these
pathogens are widely distributed. However, genetic variation is underestimated by
data biases (e.g. neglected submission of sequences to genetic databases) and low
sampling. New genotypes are likely to be discovered as sampling efforts increase
according to accumulation prediction analyses, especially for C. parvum. Our
study highlights the need for greater sampling and archiving of genotypes
globally to allow comparative analyses that help understand the population
dynamics of these protozoan parasites. Overall our study represents a
comprehensive overview for exploring local and global protozoan genotype
diversity and advances our understanding of the importance for surveillance and
potential risk associated with these infectious diseases.
PMID- 28704363
TI - Uniform multidrug therapy for leprosy patients in Brazil (U-MDT/CT-BR): Results
of an open label, randomized and controlled clinical trial, among multibacillary
patients.
AB - BACKGROUND: Leprosy control is based on early diagnosis and multidrug therapy.
For treatment purposes, leprosy patients can be classified as paucibacillary (PB)
or multibacillary (MB), according to the number of skin lesions. Studies
regarding a uniform treatment regimen (U-MDT) for all leprosy patients have been
encouraged by the WHO, rendering disease classification unnecessary. METHODOLOGY
AND FINDINGS: An independent, randomized, controlled clinical trial conducted
from 2007 to 2015 in Brazil, compared main outcomes (frequency of reactions,
bacilloscopic index trend, disability progression and relapse rates) among MB
patients treated with a uniform regimen/U-MDT (dapsone+rifampicin+clofazimine for
six months) versus WHO regular-MDT/R-MDT (dapsone+rifampicin+clofazimine for 12
months). A total of 613 newly diagnosed, untreated MB patients with high
bacterial load were included. There was no statistically significant difference
in Kaplan-Meyer survival function regarding reaction or disability progression
among patients in the U-MDT and R-MDT groups, with more than 25% disability
progression in both groups. The full mixed effects model adjusted for the
bacilloscopic index average trend in time showed no statistically significant
difference for the regression coefficient in both groups and for interaction
variables that included treatment group. During active follow up, four patients
in U-MDT group relapsed representing a relapse rate of 2.6 per 1000 patients per
year of active follow up (95% CI [0.81, 6.2] per 1000). During passive follow up
three patients relapsed in U-MDT and one in R-MTD. As this period corresponds to
passive follow up, sensitivity analysis estimated the relapse rate for the entire
follow up period between 2.9- and 4.5 per 1000 people per year. CONCLUSION: Our
results on the first randomized and controlled study on U-MDT together with the
results from three previous studies performed in China, India and Bangladesh,
support the hypothesis that UMDT is an acceptable option to be adopted in endemic
countries to treat leprosy patients in the field worldwide. TRIAL REGISTRATION:
ClinicalTrials.gov: NCT00669643.
PMID- 28704364
TI - Dramatic and concerted conformational changes enable rhodocetin to block
alpha2beta1 integrin selectively.
AB - The collagen binding integrin alpha2beta1 plays a crucial role in hemostasis,
fibrosis, and cancer progression amongst others. It is specifically inhibited by
rhodocetin (RC), a C-type lectin-related protein (CLRP) found in Malayan pit
viper (Calloselasma rhodostoma) venom. The structure of RC alone reveals a
heterotetramer arranged as an alphabeta and gammadelta subunit in a cruciform
shape. RC specifically binds to the collagen binding A-domain of the integrin
alpha2 subunit, thereby blocking collagen-induced platelet aggregation. However,
until now, the molecular basis for this interaction has remained unclear. Here,
we present the molecular structure of the RCgammadelta-alpha2A complex solved to
3.0 A resolution. Our findings show that RC undergoes a dramatic structural
reorganization upon binding to alpha2beta1 integrin. Besides the release of the
nonbinding RCalphabeta tandem, the RCgamma subunit interacts with loop 2 of the
alpha2A domain as result of a dramatic conformational change. The RCdelta subunit
contacts the integrin alpha2A domain in the "closed" conformation through its
helix C. Combined with epitope-mapped antibodies, conformationally locked alpha2A
domain mutants, point mutations within the alpha2A loop 2, and chemical
modifications of the purified toxin protein, this molecular structure of
RCgammadelta-alpha2A complex explains the inhibitory mechanism and specificity of
RC for alpha2beta1 integrin.
PMID- 28704365
TI - Central and peripheral nervous system involvement caused by Zika and chikungunya
coinfection.
PMID- 28704367
TI - Correction: Viral genetic variation accounts for a third of variability in HIV-1
set-point viral load in Europe.
AB - [This corrects the article DOI: 10.1371/journal.pbio.2001855.].
PMID- 28704366
TI - Identifying wildlife reservoirs of neglected taeniid tapeworms: Non-invasive
diagnosis of endemic Taenia serialis infection in a wild primate population.
AB - Despite the global distribution and public health consequences of Taenia
tapeworms, the life cycles of taeniids infecting wildlife hosts remain largely
undescribed. The larval stage of Taenia serialis commonly parasitizes rodents and
lagomorphs, but has been reported in a wide range of hosts that includes geladas
(Theropithecus gelada), primates endemic to Ethiopia. Geladas exhibit protuberant
larval cysts indicative of advanced T. serialis infection that are associated
with high mortality. However, non-protuberant larvae can develop in deep tissue
or the abdominal cavity, leading to underestimates of prevalence based solely on
observable cysts. We adapted a non-invasive monoclonal antibody-based enzyme
linked immunosorbent assay (ELISA) to detect circulating Taenia spp. antigen in
dried gelada urine. Analysis revealed that this assay was highly accurate in
detecting Taenia antigen, with 98.4% specificity, 98.5% sensitivity, and an area
under the curve of 0.99. We used this assay to investigate the prevalence of T.
serialis infection in a wild gelada population, finding that infection is
substantially more widespread than the occurrence of visible T. serialis cysts
(16.4% tested positive at least once, while only 6% of the same population
exhibited cysts). We examined whether age or sex predicted T. serialis infection
as indicated by external cysts and antigen presence. Contrary to the female-bias
observed in many Taenia-host systems, we found no significant sex bias in either
cyst presence or antigen presence. Age, on the other hand, predicted cyst
presence (older individuals were more likely to show cysts) but not antigen
presence. We interpret this finding to indicate that T. serialis may infect
individuals early in life but only result in visible disease later in life. This
is the first application of an antigen ELISA to the study of larval Taenia
infection in wildlife, opening the doors to the identification and description of
infection dynamics in reservoir populations.
PMID- 28704368
TI - Mouse models of 17q21.31 microdeletion and microduplication syndromes highlight
the importance of Kansl1 for cognition.
AB - Koolen-de Vries syndrome (KdVS) is a multi-system disorder characterized by
intellectual disability, friendly behavior, and congenital malformations. The
syndrome is caused either by microdeletions in the 17q21.31 chromosomal region or
by variants in the KANSL1 gene. The reciprocal 17q21.31 microduplication syndrome
is associated with psychomotor delay, and reduced social interaction. To
investigate the pathophysiology of 17q21.31 microdeletion and microduplication
syndromes, we generated three mouse models: 1) the deletion (Del/+); or 2) the
reciprocal duplication (Dup/+) of the 17q21.31 syntenic region; and 3) a
heterozygous Kansl1 (Kans1+/-) model. We found altered weight, general activity,
social behaviors, object recognition, and fear conditioning memory associated
with craniofacial and brain structural changes observed in both Del/+ and Dup/+
animals. By investigating hippocampus function, we showed synaptic transmission
defects in Del/+ and Dup/+ mice. Mutant mice with a heterozygous loss-of-function
mutation in Kansl1 displayed similar behavioral and anatomical phenotypes
compared to Del/+ mice with the exception of sociability phenotypes. Genes
controlling chromatin organization, synaptic transmission and neurogenesis were
upregulated in the hippocampus of Del/+ and Kansl1+/- animals. Our results
demonstrate the implication of KANSL1 in the manifestation of KdVS phenotypes and
extend substantially our knowledge about biological processes affected by these
mutations. Clear differences in social behavior and gene expression profiles
between Del/+ and Kansl1+/- mice suggested potential roles of other genes
affected by the 17q21.31 deletion. Together, these novel mouse models provide new
genetic tools valuable for the development of therapeutic approaches.
PMID- 28704369
TI - Clinical and parasitological factors in parasite persistence after treatment and
clinical cure of cutaneous leishmaniasis.
AB - BACKGROUND: The determinants of parasite persistence or elimination after
treatment and clinical resolution of cutaneous leishmaniasis (CL) are unknown. We
investigated clinical and parasitological parameters associated with the presence
and viability of Leishmania after treatment and resolution of CL caused by L.
Viannia. METHODS: Seventy patients who were treated with meglumine antimoniate (n
= 38) or miltefosine (n = 32) and cured, were included in this study. Leishmania
persistence and viability were determined by detection of kDNA and 7SLRNA
transcripts, respectively, before, at the end of treatment (EoT), and 13 weeks
after initiation of treatment in lesions and swabs of nasal and tonsillar mucosa.
RESULTS: Sixty percent of patients (42/70) had evidence of Leishmania persistence
at EoT and 30% (9/30) 13 weeks after treatment initiation. A previous episode of
CL was found to be a protective factor for detectable Leishmania persistence (OR:
0.16, 95%CI: 0.03-0.92). kDNA genotyping could not discern differences between
parasite populations that persisted and those isolated at diagnosis. CONCLUSIONS:
Leishmania persist in skin and mucosal tissues in a high proportion of patients
who achieved therapeutic cure of CL. This finding prompts assessment of the
contribution of persistent infection in transmission and endemicity of CL, and in
disease reactivation and protective immunity.
PMID- 28704370
TI - Insights into the sand fly saliva: Blood-feeding and immune interactions between
sand flies, hosts, and Leishmania.
AB - BACKGROUND: Leishmaniases are parasitic diseases present worldwide that are
transmitted to the vertebrate host by the bite of an infected sand fly during a
blood feeding. Phlebotomine sand flies inoculate into the mammalian host
Leishmania parasites embedded in promastigote secretory gel (PSG) with saliva,
which is composed of a diverse group of molecules with pharmacological and
immunomodulatory properties. METHODS AND FINDINGS: In this review, we focus on 3
main aspects of sand fly salivary molecules: (1) structure and composition of
salivary glands, including the properties of salivary molecules related to
hemostasis and blood feeding, (2) immunomodulatory properties of salivary
molecules and the diverse impacts of these molecules on leishmaniasis, ranging
from disease exacerbation to vaccine development, and (3) use of salivary
molecules for field applications, including monitoring host exposure to sand
flies and the risk of Leishmania transmission. Studies showed interesting
differences between salivary proteins of Phlebotomus and Lutzomyia species,
however, no data were ever published on salivary proteins of Sergentomyia
species. CONCLUSIONS: In the last 15 years, numerous studies have characterized
sand fly salivary proteins and, in parallel, have addressed the impact of such
molecules on the biology of the host-sand fly-parasite interaction. The results
obtained shall pave the way for the development of field-application tools that
could contribute to the management of leishmaniasis in endemic areas.
PMID- 28704371
TI - Genetic compensation: A phenomenon in search of mechanisms.
AB - Several recent studies in a number of model systems including zebrafish,
Arabidopsis, and mouse have revealed phenotypic differences between knockouts
(i.e., mutants) and knockdowns (e.g., antisense-treated animals). These
differences have been attributed to a number of reasons including off-target
effects of the antisense reagents. An alternative explanation was recently
proposed based on a zebrafish study reporting that genetic compensation was
observed in egfl7 mutant but not knockdown animals. Dosage compensation was first
reported in Drosophila in 1932, and genetic compensation in response to a gene
knockout was first reported in yeast in 1969. Since then, genetic compensation
has been documented many times in a number of model organisms; however, our
understanding of the underlying molecular mechanisms remains limited. In this
review, we revisit studies reporting genetic compensation in higher eukaryotes
and outline possible molecular mechanisms, which may include both transcriptional
and posttranscriptional processes.
PMID- 28704372
TI - The ancestral levels of transcription and the evolution of sexual phenotypes in
filamentous fungi.
AB - Changes in gene expression have been hypothesized to play an important role in
the evolution of divergent morphologies. To test this hypothesis in a model
system, we examined differences in fruiting body morphology of five filamentous
fungi in the Sordariomycetes, culturing them in a common garden environment and
profiling genome-wide gene expression at five developmental stages. We
reconstructed ancestral gene expression phenotypes, identifying genes with the
largest evolved increases in gene expression across development. Conducting
knockouts and performing phenotypic analysis in two divergent species typically
demonstrated altered fruiting body development in the species that had evolved
increased expression. Our evolutionary approach to finding relevant genes proved
far more efficient than other gene deletion studies targeting whole genomes or
gene families. Combining gene expression measurements with knockout phenotypes
facilitated the refinement of Bayesian networks of the genes underlying fruiting
body development, regulation of which is one of the least understood processes of
multicellular development.
PMID- 28704373
TI - Possible roles of mechanical cell elimination intrinsic to growing tissues from
the perspective of tissue growth efficiency and homeostasis.
AB - Cell competition is a phenomenon originally described as the competition between
cell populations with different genetic backgrounds; losing cells with lower
fitness are eliminated. With the progress in identification of related molecules,
some reports described the relevance of cell mechanics during elimination.
Furthermore, recent live imaging studies have shown that even in tissues composed
of genetically identical cells, a non-negligible number of cells are eliminated
during growth. Thus, mechanical cell elimination (MCE) as a consequence of
mechanical cellular interactions is an unavoidable event in growing tissues and a
commonly observed phenomenon. Here, we studied MCE in a genetically-homogeneous
tissue from the perspective of tissue growth efficiency and homeostasis. First,
we propose two quantitative measures, cell and tissue fitness, to evaluate
cellular competitiveness and tissue growth efficiency, respectively. By
mechanical tissue simulation in a pure population where all cells have the same
mechanical traits, we clarified the dependence of cell elimination rate or cell
fitness on different mechanical/growth parameters. In particular, we found that
geometrical (specifically, cell size) and mechanical (stress magnitude)
heterogeneities are common determinants of the elimination rate. Based on these
results, we propose possible mechanical feedback mechanisms that could improve
tissue growth efficiency and density/stress homeostasis. Moreover, when cells
with different mechanical traits are mixed (e.g., in the presence of phenotypic
variation), we show that MCE could drive a drastic shift in cell trait
distribution, thereby improving tissue growth efficiency through the selection of
cellular traits, i.e. intra-tissue "evolution". Along with the improvement of
growth efficiency, cell density, stress state, and phenotype (mechanical traits)
were also shown to be homogenized through growth. More theoretically, we propose
a mathematical model that approximates cell competition dynamics, by which the
time evolution of tissue fitness and cellular trait distribution can be predicted
without directly simulating a cell-based mechanical model.
PMID- 28704374
TI - Spatial organization of the budding yeast genome in the cell nucleus and
identification of specific chromatin interactions from multi-chromosome
constrained chromatin model.
AB - Nuclear landmarks and biochemical factors play important roles in the
organization of the yeast genome. The interaction pattern of budding yeast as
measured from genome-wide 3C studies are largely recapitulated by model polymer
genomes subject to landmark constraints. However, the origin of inter-chromosomal
interactions, specific roles of individual landmarks, and the roles of
biochemical factors in yeast genome organization remain unclear. Here we describe
a multi-chromosome constrained self-avoiding chromatin model (mC-SAC) to gain
understanding of the budding yeast genome organization. With significantly
improved sampling of genome structures, both intra- and inter-chromosomal
interaction patterns from genome-wide 3C studies are accurately captured in our
model at higher resolution than previous studies. We show that nuclear
confinement is a key determinant of the intra-chromosomal interactions, and
centromere tethering is responsible for the inter-chromosomal interactions. In
addition, important genomic elements such as fragile sites and tRNA genes are
found to be clustered spatially, largely due to centromere tethering. We
uncovered previously unknown interactions that were not captured by genome-wide
3C studies, which are found to be enriched with tRNA genes, RNAPIII and TFIIS
binding. Moreover, we identified specific high-frequency genome-wide 3C
interactions that are unaccounted for by polymer effects under landmark
constraints. These interactions are enriched with important genes and likely play
biological roles.
PMID- 28704375
TI - The effect of the promiscuity stereotype on opposition to gay rights.
AB - Opposition to gay rights is prevalent in countries around the world. Recent
correlational research suggests that opposition to gay rights may be driven by an
interaction between one's own short-term mating orientation (i.e. willingness to
engage in casual sex) and representations of gay people as sexually promiscuous.
Here, we experimentally manipulated representations of gay men by randomly
assigning participants to read one of two versions of a fictitious newspaper
article, one of which contained faux scientific evidence confirming the
stereotype that gay men are promiscuous, and the other containing faux scientific
evidence refuting the stereotype. We found that the manipulation interacted with
short-term mating orientation (STMO) to predict opposition to gay rights, such
that low-STMO individuals (i.e. more averse to casual sex) exhibited more support
for gay rights when assigned to read the stereotype-refuting article compared to
the stereotype-confirming article, whereas high-STMO individuals (i.e. less
averse to casual sex) were not significantly influenced by the manipulation. We
discuss the implications of these findings for the study of antigay attitudes, as
well as for recent societal changes in acceptance of homosexuality.
PMID- 28704376
TI - Effectiveness of rapid rail transit system in Beijing.
AB - The effectiveness of rapid rail transit system is analyzed using tools of complex
network for the first time. We evaluated the effectiveness of the system in
Beijing quantitatively from different perspectives, including descriptive
statistics analysis, bridging property, centrality property, ability of
connecting different part of the system and ability of disease spreading. The
results showed that the public transport of Beijing does benefit from the rapid
rail transit lines, and the benefit of different regions from RRTS is gradually
decreased from the north to the south. The paper concluded with some policy
suggestions regarding how to promote the system. This study offered significant
insight that can help understand the public transportation better. The
methodology can be easily applied to analyze other urban public systems, such as
electricity grid, water system, to develop more livable cities.
PMID- 28704377
TI - A cluster-randomized controlled study to evaluate a team coaching concept for
improving teamwork and patient-centeredness in rehabilitation teams.
AB - PURPOSE: Although the relevance of interprofessional teamwork in the delivery of
patient-centered care is well known, there is a lack of interventions for
improving team interaction in the context of rehabilitation in Germany. The aim
of the present study is to evaluate whether a specially developed team coaching
concept (TCC) could improve both teamwork and patient-centeredness. METHOD: A
multicenter, cluster-randomized controlled intervention study was conducted with
both staff and patient questionnaires. Data was collected at ten German
rehabilitation clinics (five clusters) of different indication fields before (t1)
and after (t2) the intervention. Intervention clinics received the TCC, while
control clinics did not receive any treatment. Staff questionnaires were used to
measure internal participation and other aspects of teamwork, such as team
organization, while patient questionnaires assessed patient-centeredness. A
multivariate analysis of variance was applied for data analysis. RESULTS: In
order to analyze the effect of TCC on internal participation and teamwork, 305
questionnaires were included for t1 and 213 for t2 in the staff survey. In the
patient survey, 523 questionnaires were included for t1 and 545 for t2. The TCC
improved team organization, willingness to accept responsibility and knowledge
integration according to staff, with small effect sizes (univariate: eta2=.010
.017), whereas other parameters including internal participation, team leadership
and cohesion did not improve due to the intervention. The patient survey did not
show any improvements on the assessed dimensions. CONCLUSION: The TCC improved
dimensions that were addressed directly by the approach and were linked to the
clinics' needs, such as restructured team meetings and better exchange of
information. The TCC can be used to improve team organization, willingness to
accept responsibility, and knowledge integration in rehabilitation practice, but
some further evaluation is needed to understand contextual factors and processes
regarding the implementation of the intervention.
PMID- 28704378
TI - Characterizing properties of non-estrogenic substituted bisphenol analogs using
high throughput microscopy and image analysis.
AB - Animal studies have linked the estrogenic properties of bisphenol A (BPA) to
adverse effects on the endocrine system. Because of concerns for similar effects
in humans, there is a desire to replace BPA in consumer products, and a search
for BPA replacements that lack endocrine-disrupting bioactivity is ongoing. We
used multiple cell-based models, including an established multi-parametric, high
throughput microscopy-based platform that incorporates engineered HeLa cell lines
with visible ERalpha- or ERbeta-regulated transcription loci, to discriminate the
estrogen-like and androgen-like properties of previously uncharacterized
substituted bisphenol derivatives and hydroquinone. As expected, BPA induced 70
80% of the estrogen-like activity via ERalpha and ERbeta compared to E2 in the
HeLa prolactin array cell line. 2,2' BPA, Bisguaiacol F, CHDM 4-hydroxybuyl
acrylate, hydroquinone, and TM modified variants of BPF showed very limited
estrogen-like or androgen-like activity (< 10% of that observed with the control
compounds). Interestingly, TM-BFP and CHDM 4-hydroxybuyl acrylate, but not their
derivatives, demonstrated evidence of anti-estrogenic and anti-androgenic
activity. Our findings indicate that Bisguaiacol F, TM-BFP-ER and TM-BPF-DGE
demonstrate low potential for affecting estrogenic or androgenic endocrine
activity. This suggest that the tested compounds could be suitable commercially
viable alternatives to BPA.
PMID- 28704379
TI - Fractionating nonword repetition: The contributions of short-term memory and
oromotor praxis are different.
AB - The ability to reproduce novel words is a sensitive marker of language impairment
across a variety of developmental disorders. Nonword repetition tasks are thought
to reflect phonological short-term memory skills. Yet, when children hear and
then utter a word for the first time, they must transform a novel speech signal
into a series of coordinated, precisely timed oral movements. Little is known
about how children's oromotor speed, planning and co-ordination abilities might
influence their ability to repeat novel nonwords, beyond the influence of higher
level cognitive and linguistic skills. In the present study, we tested 35
typically developing children between the ages of 5-8 years on measures of
nonword repetition, digit span, memory for non-verbal sequences, reading fluency,
oromotor praxis, and oral diadochokinesis. We found that oromotor praxis uniquely
predicted nonword repetition ability in school-age children, and that the
variance it accounted for was additional to that of digit span, memory for non
verbal sequences, articulatory rate (measured by oral diadochokinesis) as well as
reading fluency. We conclude that the ability to compute and execute novel
sensorimotor transformations affects the production of novel words. These results
have important implications for understanding motor/language relations in
neurodevelopmental disorders.
PMID- 28704380
TI - Molecular investigation by whole exome sequencing revealed a high proportion of
pathogenic variants among Thai victims of sudden unexpected death syndrome.
AB - INTRODUCTION: Sudden unexpected death syndrome (SUDS) is an important cause of
death in young healthy adults with a high incident rate in Southeast Asia;
however, there are no molecular autopsy reports about these victims. We performed
a combination of both a detailed autopsy and a molecular autopsy by whole exome
sequencing (WES) to investigate the cause of SUDS in Thai sudden death victims.
MATERIALS AND METHODS: A detailed forensic autopsy was performed to identify the
cause of death, followed by a molecular autopsy, in 42 sudden death victims who
died between January 2015 and August 2015. The coding sequences of 98 SUDS
related genes were sequenced using WES. Potentially causative variants were
filtered based on the variant functions annotated in the dbNSFP database.
Variants with inconclusive clinical significance evidence in ClinVar were
resolved with a variant prediction algorithm, metaSVM, and the frequency data of
the variants found in public databases, such as the 1000 Genome Project, ESP6500
project, and the Exome Aggregation Consortium (ExAc) project. RESULTS: Combining
both autopsy and molecular autopsy enabled the potential identification of cause
of death in 81% of the cases. Among the 25 victims with WES data, 72% (18/25)
were found to have potentially causative SUDS mutations. The majority of the
victims had at a mutation in the TTN gene (8/18 = 44%), and only one victim had
an SCN5A mutation. CONCLUSIONS: WES can help to identify the genetic causes in
victims of SUDS and may help to further guide investigations into their relatives
to prevent additional SUDS victims.
PMID- 28704381
TI - Sofosbuvir based treatment of chronic hepatitis C genotype 3 infections-A
Scandinavian real-life study.
AB - BACKGROUND AND AIMS: Chronic hepatitis C virus (HCV) genotype 3 infection with
advanced liver disease has emerged as the most challenging to treat. We
retrospectively assessed the treatment outcome of sofosbuvir (SOF) based regimes
for treatment of HCV genotype 3 infections in a real life setting in Scandinavia.
METHODS: Consecutive patients with chronic HCV genotype 3 infection were enrolled
at 16 treatment centers in Denmark, Sweden, Norway and Finland. Patients who had
received a SOF containing regimen were included. The fibrosis stage was evaluated
by liver biopsy or transient liver elastography. The following treatments were
given according availability and local guidelines: 1) SOF + ribavirin (RBV) for
24 weeks, 2) SOF + daclatasvir (DCV) +/-RBV for 12-24 weeks, 3) SOF + pegylated
interferon alpha (peg-IFN-alpha) + RBV for 12 weeks or 4) SOF/ledipasvir (LDV) +
RBV for 12-16 weeks. The primary endpoint was sustained virological response
(SVR) assessed at week 12 (SVR12) after end of treatment. RESULTS: We included
316 patients with a mean age of 55 years (range 24-79), 70% men, 49% treatment
experienced, 58% with compensated cirrhosis and 12% with decompensated
cirrhosis.In the modified intention to treat (mITT) population SVR12 was achieved
in 284/311 (91%) patients. Among 26 treatment failures, five had non-response, 3
breakthrough and 18 relapse. Five patients were not included in the mITT
population. Three patients died from reasons unrelated to treatment and two were
lost to follow-up. The SVR12 rate was similar for all treatment regimens, but
lower in men (p = 0.042), and in patients with decompensated liver disease (p =
0.004). CONCLUSION: We found that sofosbuvir based treatment in a real-life
setting could offer SVR rates exceeding 90% in patients with HCV genotype 3
infection and advanced liver disease.
PMID- 28704382
TI - Identifying the perceptive users for online social systems.
AB - In this paper, the perceptive user, who could identify the high-quality objects
in their initial lifespan, is presented. By tracking the ratings given to the
rewarded objects, we present a method to identify the user perceptibility, which
is defined as the capability that a user can identify these objects at their
early lifespan. Moreover, we investigate the behavior patterns of the perceptive
users from three dimensions: User activity, correlation characteristics of user
rating series and user reputation. The experimental results for the empirical
networks indicate that high perceptibility users show significantly different
behavior patterns with the others: Having larger degree, stronger correlation of
rating series and higher reputation. Furthermore, in view of the hysteresis in
finding the rewarded objects, we present a general framework for identifying the
high perceptibility users based on user behavior patterns. The experimental
results show that this work is helpful for deeply understanding the collective
behavior patterns for online users.
PMID- 28704383
TI - Predicting in-hospital death during acute presentation with pulmonary embolism to
facilitate early discharge and outpatient management.
AB - BACKGROUND: Pulmonary embolism continues to be a significant cause of death. The
aim was to derive and validate a risk prediction model for in-hospital death
after acute pulmonary embolism to identify low risk patients suitable for
outpatient management. METHODS: A confirmed acute pulmonary embolism database of
1,426 consecutive patients admitted to a tertiary-center (2000-2012) was
analyzed, with odd and even years as derivation and validation cohorts
respectively. Risk stratification for in-hospital death was performed using
multivariable logistic-regression modelling. Models were compared using receiver
operating characteristic-curve and decision curve analyses. RESULTS: In-hospital
mortality was 3.6% in the derivation cohort (n = 693). Adding day-1 sodium and
bicarbonate to simplified Pulmonary Embolism Severity Index (sPESI) significantly
increased the C-statistic for predicting in-hospital death (0.71 to 0.86, P =
0.001). The validation cohort yielded similar results (n = 733, C-statistic
0.85). The new model was associated with a net reclassification improvement of
0.613, and an integrated discrimination improvement of 0.067. The new model also
increased the C-statistic for predicting 30-day mortality compared to sPESI alone
(0.74 to 0.83, P = 0.002). Decision curve analysis demonstrated superior clinical
benefit with the use of the new model to guide admission for pulmonary embolism,
resulting in 43 fewer admissions per 100 presentations based on a risk threshold
for admission of 2%. CONCLUSIONS: A risk model incorporating sodium, bicarbonate,
and the sPESI provides accurate risk prediction of acute in-hospital mortality
after pulmonary embolism. Our novel model identifies patients with pulmonary
embolism who are at low risk and who may be suitable for outpatient management.
PMID- 28704384
TI - Quantitative thyroglobulin response to radioactive iodine treatment in predicting
radioactive iodine-refractory thyroid cancer with pulmonary metastasis.
AB - OBJECTIVE: Current diagnosis of radioactive iodine (RAI)-refractory (RAIR)
differentiated thyroid cancer (DTC) is based on the imaging technique, which is
of a high cost. Serum thyroglobulin (Tg) is a sensitive and easily obtained
biomarker. Hence, we aimed to assess the predicting value of quantitative
response of Tg in earlier identifying the RAIR-DTC with pulmonary metastasis.
PATIENTS AND METHODS: Pulmonary metastatic DTC patients who underwent total or
near-total thyroidectomy and at least two times of RAI therapy were included in
this study. The pre-ablative stimulated Tg at the first and second RAI therapy
were defined as pstim-Tg1 and pstim-Tg2, while the suppressed Tg before and after
the second RAI therapy were designated sup-Tg1 and sup-Tg2. The predicted value
of pstim-Tg2/Tg1 and sup-Tg2/Tg1 ratio were detected using the receiver operating
characteristic (ROC) curve and logistic regression analyses. RESULTS: Totally 115
patients were involved in this study. ROC curves showed a cut-off value of 0.544
for pstim-Tg2/ pstim-Tg1 in detecting RAIR, with a sensitivity of 0.9 and
specificity of 0.477, and an area under the curve (AUC) of 0.744. Similarly, the
cut-off of sup-Tg2/ sup-Tg1 was 0.972, with a sensitivity of 0.733 and
specificity of 0.935, and AUC of 0.898. Univariate analysis illustrated that age,
tumor size, pstim-Tg2/Tg1, sup-Tg2/ sup-Tg1 and BRAFV600E mutation were eligible
to predict RAIR. While from multivariate analysis, only age, pstim-Tg2/Tg1, sup
Tg2/ sup-Tg1 and BRAFV600E mutation were verified to be the independent
predictive factors. CONCLUSION: The quantitative Tg response was encouraging in
identifying RAIR-DTC with pulmonary metastasis. Age, BRAFV600E mutation and Tg
response were independent predictors in predicting RAIR-DTC.
PMID- 28704385
TI - Immunoprotective properties of recombinant LigA and LigB in a hamster model of
acute leptospirosis.
AB - Leptospirosis is the most widespread zoonosis and is considered a major public
health problem worldwide. Currently, there is no widely available vaccine against
leptospirosis for use in humans. A purified, recombinant subunit vaccine that
includes the last six immunoglobulin-like (Ig-like) domains of the leptospiral
protein LigA (LigA7'-13) protects against lethal infection but not renal
colonization after challenge by Leptospira interrogans. In this study, we
examined whether the addition of the first seven Ig-like domains of LigB (LigB0
7) to LigA7'-13, can enhance immune protection and confer sterilizing immunity in
the Golden Syrian hamster model of acute leptospirosis. Hamsters were
subcutaneously immunized with soluble, recombinant LigA7'-13, LigB0-7, or a
combination of LigA7'-13 and LigB0-7 in Freund's adjuvant. Immunization with Lig
proteins generated a strong humoral immune response with high titers of IgG that
recognized homologous protein, and cross-reacted with the heterologous protein as
assessed by ELISA. LigA7'-13 alone, or in combination with LigB0-7, protected all
hamsters from intraperitoneal challenge with a lethal dose of L. interrogans
serovar Copenhageni strain Fiocruz L1-130. However, bacteria were recovered from
the kidneys of all animals. Of eight animals immunized with LigB0-7, only three
survived Leptospira challenge, one of which lacked renal colonization and had
antibodies to native LigB by immunoblot. In addition, sera from two of the three
LigB0-7 immunized survivors cross-reacted with LigA11-13, a region of LigA that
is sufficient for protection. In summary, we confirmed that LigA7'-13 protects
hamsters from death but not infection, and immunization with LigB0-7, either
alone or in combination with LigA7'-13, did not confer sterilizing immunity.
PMID- 28704386
TI - Nannochloropsis oceania-derived defatted meal as an alternative to fishmeal in
Atlantic salmon feeds.
AB - Defatted microalgal biomass derived from biorefinery can be potential feed
ingredients for carnivorous fish. The present study investigated the growth, feed
intake:gain and health parameters in Atlantic salmon fed for 84 days with
defatted Nannochloropsis oceania as a fishmeal replacer. Fish fed feeds
containing the algal biomass (at 10 and 20% inclusion, alga groups) were compared
with groups that consumed alga-devoid feeds (control group). The fish that
received 20% alga tended to have reduced weight gain and specific growth rate.
Condition factor, feed conversion ratio and feed intake of this fish group were
significantly different when compared with the control group. Hepatosomatic and
viscerosomatic indices, whole body and fillet proximate composition were not
affected by the dietary treatments. Digestibility of dry matter, protein, lipid,
ash and energy, as well as retention of lipid and energy of the fish that
received feed with 20% alga meal were also significantly different from those of
the control group. Serum superoxide dismutase activity of the 10% alga-fed fish
was significantly higher compared with the control fish. Although alga feeding
did not cause any distal intestinal inflammation, the intestinal proteins that
were altered upon feeding 20% algal meal might be pointing to systemic
physiological disturbances. In conclusion, feeds with 20% alga had a negative
effect on feed intake, FCR, lipid and energy retention and health of the fish.
The defatted Nannochloropsis oceania can be used at modest inclusion levels,
around 10%, without negative effects on the performance of Atlantic salmon.
PMID- 28704387
TI - Abundance of commercially important reef fish indicates different levels of over
exploitation across shelves of the U.S. Virgin Islands.
AB - The United States Virgin Islands are comprised of two separate insular platforms
separated by the deep water Anegada Passage. Although managed by the same
regulations, as one fishery, several physical and spatial differences exist
between the two northern shelf islands, St. Thomas and St. John, and isolated St.
Croix. Based on two long-term fisheries independent datasets, collected by the
U.S. Virgin Islands Territorial Coral Reef Monitoring Program and the National
Oceanographic and Atmospheric Administration Center for Coastal Monitoring and
Assessment, there were significant differences between the northern USVI and St.
Croix in both the occurrence and size of several species of large and
commercially important reef fishes. These fishes are primarily apex piscivores
and generally the first species over-exploited in small-scale fisheries. The
disparities between the fish communities on the two island shelves cannot be
explained solely by differences in habitat (coral cover, rugosity) or fisheries
management, such as relative amount of marine protected area in local waters.
They are instead probably caused by a combination of several other interrelated
factors including water depth, fishing methodology, fishable area, and the
presence or absence of viable fish spawning areas. This study considers those
aspects, and illustrates the need for management of island artisanal fisheries
that is tailored to the physical and spatial constraints imposed by insular
platforms.
PMID- 28704389
TI - Differential chromatin profiles partially determine transcription factor binding.
AB - We characterize how genomic variants that alter chromatin accessibility influence
regulatory factor binding with a new method called DeltaBind that predicts
condition specific factor binding more accurately than other methods based on
DNase-seq data. Using DeltaBind and DNase-seq experiments we predicted the
differential binding of 18 factors in K562 and GM12878 cells with an average
precision of 28% at 10% recall, with the prediction of individual factors ranging
from 5% to 65% precision. We further found that genome variants that alter
chromatin accessibility are not necessarily predictive of altering proximal
factor binding. Taken together these findings suggest that DNase-seq or ATAC-seq
Quantitative Trait Loci (dsQTLs), while important, must be considered in a
broader context to establish causality for phenotypic changes.
PMID- 28704388
TI - The miR-23a~27a~24-2 microRNA cluster buffers transcription and signaling
pathways during hematopoiesis.
AB - MicroRNA cluster mirn23a has previously been shown to promote myeloid development
at the expense of lymphoid development in overexpression and knockout mouse
models. This polarization is observed early in hematopoietic development, with an
increase in common lymphoid progenitors (CLPs) and a decrease in all myeloid
progenitor subsets in adult bone marrow. The pool size of multipotential
progenitors (MPPs) is unchanged; however, in this report we observe by flow
cytometry that polarized subsets of MPPs are changed in the absence of mirn23a.
Additionally, in vitro culture of MPPs and sorted MPP transplants showed that
these cells have decreased myeloid and increased lymphoid potential in vitro and
in vivo. We investigated the mechanism by which mirn23a regulates hematopoietic
differentiation and observed that mirn23a promotes myeloid development of
hematopoietic progenitors through regulation of hematopoietic transcription
factors and signaling pathways. Early transcription factors that direct the
commitment of MPPs to CLPs (Ikzf1, Runx1, Satb1, Bach1 and Bach2) are increased
in the absence of mirn23a miRNAs as well as factors that commit the CLP to the B
cell lineage (FoxO1, Ebf1, and Pax5). Mirn23a appears to buffer transcription
factor levels so that they do not stochastically reach a threshold level to
direct differentiation. Intriguingly, mirn23a also inversely regulates the PI3
kinase (PI3K)/Akt and BMP/Smad signaling pathways. Pharmacological inhibitor
studies, coupled with dominant active/dominant negative biochemical experiments,
show that both signaling pathways are critical to mirn23a's regulation of
hematopoietic differentiation. Lastly, consistent with mirn23a being a
physiological inhibitor of B cell development, we observed that the essential B
cell transcription factor EBF1 represses expression of mirn23a. In summary, our
data demonstrates that mirn23a regulates a complex array of transcription and
signaling pathways to modulate adult hematopoiesis.
PMID- 28704390
TI - Inter-rater reliability of categorical versus continuous scoring of fish
vitality: Does it affect the utility of the reflex action mortality predictor
(RAMP) approach?
AB - Scoring reflex responsiveness and injury of aquatic organisms has gained
popularity as predictors of discard survival. Given this method relies upon the
individual interpretation of scoring criteria, an evaluation of its robustness is
done here to test whether protocol-instructed, multiple raters with diverse
backgrounds (research scientist, technician, and student) are able to produce
similar or the same reflex and injury score for one of the same flatfish
(European plaice, Pleuronectes platessa) after experiencing commercial fishing
stressors. Inter-rater reliability for three raters was assessed by using a 3
point categorical scale ('absent', 'weak', 'strong') and a tagged visual analogue
continuous scale (tVAS, a 10 cm bar split in three labelled sections: 0 for
'absent', 'weak', 'moderate', and 'strong') for six reflex responses, and a 4
point scale for four injury types. Plaice (n = 304) were sampled from 17 research
beam-trawl deployments during four trips. Fleiss kappa (categorical scores) and
intra-class correlation coefficients (ICC, continuous scores) indicated variable
inter-rater agreement by reflex type (ranging between 0.55 and 0.88, and 67% and
91% for Fleiss kappa and ICC, respectively), with least agreement among raters on
extent of injury (Fleiss kappa between 0.08 and 0.27). Despite differences among
raters, which did not significantly influence the relationship between impairment
and predicted survival, combining categorical reflex and injury scores always
produced a close relationship of such vitality indices and observed delayed
mortality. The use of the continuous scale did not improve fit of these models
compared with using the reflex impairment index based on categorical scores.
Given these findings, we recommend using a 3-point categorical over a continuous
scale. We also determined that training rather than experience of raters
minimised inter-rater differences. Our results suggest that cost-efficient reflex
impairment and injury scoring may be considered a robust technique to evaluate
lethal stress and damage of this flatfish species on-board commercial beam-trawl
vessels.
PMID- 28704391
TI - Visceral leishmaniasis in an environmentally protected area in southeastern
Brazil: Epidemiological and laboratory cross-sectional investigation of
phlebotomine fauna, wild hosts and canine cases.
AB - BACKGROUND: Leishmaniasis is a rapidly expanding zoonosis that shows increasing
urbanization. Concern exists regarding the role of wildlife in visceral
leishmaniasis (VL) transmission, due to frequent natural or anthropogenic
environmental changes that facilitate contact between wildlife, humans and their
pets. The municipality of Campinas, in southeastern Brazil, initially recorded VL
in 2009, when the first autochthonous case was confirmed in a dog living in an
upscale residential condominium, located inside an environmentally protected area
(EPA). Since then, disease transmission remains restricted to dogs inhabiting two
geographically contiguous condominiums within the EPA. METHODOLOGY/PRINCIPAL
FINDINGS: We conducted a cross-sectional study of the VL focus to investigate
Leishmania spp. infection in domestic dogs, wild mammals and sand flies using
molecular tools and recommended serological techniques. Canine seroprevalences of
1.5% and 1.2% were observed in 2013 and 2015, respectively. Six insect species,
confirmed or suspected vectors or potential transmitters of Leishmania, were
identified. Two specimens of the main L. (L.) infantum vector in Brazil,
Lutzomyia longipalpis, were captured in the EPA. Natural infection by L. (L.)
infantum was recorded in one Expapillata firmatoi specimen and two Pintomyia
monticola. Natural infection by L. (L.) infantum and Leishmania subgenus Viannia
was also detected in two white-eared opossums (Didelphis albiventris), a known
reservoir of VL. Geographical coordinates of each sampling of infected animals
were plotted on a map of the EPA, demonstrating proximity between these animals,
human residences, including the dogs positive for VL, and forest areas.
CONCLUSIONS/SIGNIFICANCE: The EPA, which is inhabited by humans, has an active VL
focus. The risk of establishing and maintaining disease transmission foci in
similar scenarios, i.e. wild areas that undergo environmental modifications, is
evident. Moreover, different epidemiological profiles of VL must be included to
elaborate prevention and control measures that consider the particularities of
each transmission area.
PMID- 28704392
TI - Redifferentiation of aged human articular chondrocytes by combining bone
morphogenetic protein-2 and melanoma inhibitory activity protein in 3D-culture.
AB - Melanoma inhibitory activity (MIA) affects the differentiation to hyaline
cartilage and can inhibit the osteogenic potential of bone morphogenetic protein
(BMP)-2 in mesenchymal stem cells (MSC). The aim of this study was to investigate
if MIA also inhibits the osteogenic potential of BMP-2 in human articular
chondrocytes during redifferentiation, which may lead to a higher grade of
differentiation without calcification. HAC of four female patients (mean age:
73.75 +/-6.98) were seeded into 3D culture for 28 days; after adding the
recombinant proteins, four groups were formed (Control, BMP-2, MIA, BMP-2+MIA).
Samples were analysed for gene expression, glycosaminoglycan (GAG) content and
histology on day 0, 14 and 28. Collagen type 2 (COL2A1) was significantly
increased in the BMP-2 containing groups on day 28; BMP-2 (100-fold, p = 0.001),
BMP-2+MIA (65-fold, p = 0.009) and similar to the level of native cartilage.
Higher aggrecan (Agg) levels were present in the BMP-2 (3-fold, p = 0.007) and
BMP-2+MIA (4-fold, p = 0.002) group after 14 days and in the BMP-2 (9-fold, p =
0.001) group after 28 days. Collagen type 10 (COL10A1) was increased in the BMP-2
containing groups (6-fold, p = 0.006) but these levels were significantly below
native cartilage. Alkaline phosphatase (ALP), collagen type 1 (COL1A1) and the
glycosaminoglycan (GAG) content did not reveal any relevant differences between
groups. BMP-2 is a potent inducer for differentiation of HAC. A significant
enhancement of this effect in combination with MIA could not be observed.
Furthermore no significant reduction of osteogenic markers during re
differentiation of chondrocytes was present combining BMP-2 and MIA.
PMID- 28704393
TI - Whole exome sequence-based association analyses of plasma amyloid-beta in African
and European Americans; the Atherosclerosis Risk in Communities-Neurocognitive
Study.
AB - OBJECTIVE: We performed single-variant and gene-based association analyses of
plasma amyloid-beta (abeta) concentrations using whole exome sequence from 1,414
African and European Americans. Our goal was to identify genes that influence
plasma abeta42 concentrations and abeta42:abeta40 ratios in late middle age (mean
= 59 years), old age (mean = 77 years), or change over time (mean = 18 years).
METHODS: Plasma abeta measures were linearly regressed onto age, gender, APOE
epsilon4 carrier status, and time elapsed between visits (fold-changes only)
separately by race. Following inverse normal transformation of the residuals,
seqMeta was used to conduct race-specific single-variant and gene-based
association tests while adjusting for population structure. Linear regression
models were fit on autosomal variants with minor allele frequencies (MAF)>=1%. T5
burden and Sequence Kernel Association (SKAT) gene-based tests assessed
functional variants with MAF<=5%. Cross-race fixed effects meta-analyses were
Bonferroni-corrected for the number of variants or genes tested. RESULTS: Seven
genes were associated with abeta in late middle age or change over time; no
associations were identified in old age. Single variants in KLKB1 (rs3733402; p =
4.33x10-10) and F12 (rs1801020; p = 3.89x10-8) were significantly associated with
midlife abeta42 levels through cross-race meta-analysis; the KLKB1 variant
replicated internally using 1,014 additional participants with exome chip.
ITPRIP, PLIN2, and TSPAN18 were associated with the midlife abeta42:abeta40 ratio
via the T5 test; TSPAN18 was significant via the cross-race meta-analysis,
whereas ITPRIP and PLIN2 were European American-specific. NCOA1 and NT5C3B were
associated with the midlife abeta42:abeta40 ratio and the fold-change in abeta42,
respectively, via SKAT in African Americans. No associations replicated
externally (N = 725). CONCLUSION: We discovered age-dependent genetic effects,
established associations between vascular-related genes (KLKB1, F12, PLIN2) and
midlife plasma abeta levels, and identified a plausible Alzheimer's Disease
candidate gene (ITPRIP) influencing cell death. Plasma abeta concentrations may
have dynamic biological determinants across the lifespan; plasma abeta study
designs or analyses must consider age.
PMID- 28704394
TI - Genome wide host gene expression analysis in mice experimentally infected with
Pasteurella multocida.
AB - Pasteurella multocida causes acute septicemic and respiratory diseases, including
haemorrhagic septicaemia, in cattle and buffalo with case fatality of 100%. In
the present study, mice were infected with P. multocida (1.6 * 103 cfu,
intraperitoneal) to evaluate host gene expression profile at early and late
stages of infection using high throughput microarray transcriptome analyses.
Several differentially expressed genes (DEGs) at both the time points were
identified in P.multocida infected spleen, liver and lungs. Functional annotation
of these DEGs showed enrichment of key pathways such as TLR, NF-kappaB, MAPK,
TNF, JAK-STAT and NOD like receptor signaling pathways. Several DEGs overlapped
across different KEGG pathways indicating a crosstalk between them. The predicted
protein-protein interaction among these DEGs suggested, that the recognition of
P. multocida LPS or outer membrane components by TLR4 and CD14, results in
intracellular signaling via MyD88, IRAKs and/or TRAF6 leading to activation of
NFkappaB and MAPK pathways and associated cytokines.
PMID- 28704395
TI - Intraperitoneal pyrophosphate treatment reduces renal calcifications in Npt2a
null mice.
AB - Mutations in the proximal tubular sodium-dependent phosphate co-transporters
NPT2a and NPT2c have been reported in patients with renal stone disease and
nephrocalcinosis, however the relative contribution of genotype, dietary calcium
and phosphate, and modifiers of mineralization such as pyrophosphate (PPi) to the
formation of renal mineral deposits is unclear. In the present study, we used
Npt2a-/- mice to model the renal calcifications observed in these disorders. We
observed elevated urinary excretion of PPi in Npt2a-/- mice when compared to WT
mice. Presence of two hypomorphic Extracellular nucleotide pyrophosphatase
phosphodiesterase 1 (Enpp1asj/asj) alleles decreased urine PPi and worsened renal
calcifications in Npt2a-/- mice. These studies suggest that PPi is a thus far
unrecognized factor protecting Npt2a-/- mice from the development of renal
mineral deposits. Consistent with this conclusion, we next showed that renal
calcifications in these mice can be reduced by intraperitoneal administration of
sodium pyrophosphate. If confirmed in humans, urine PPi could therefore be of
interest for developing new strategies to prevent the nephrocalcinosis and
nephrolithiasis seen in phosphaturic disorders.
PMID- 28704396
TI - Phenotypic, chemical and functional characterization of cyclic nucleotide
phosphodiesterase 4 (PDE4) as a potential anthelmintic drug target.
AB - BACKGROUND: Reliance on just one drug to treat the prevalent tropical disease,
schistosomiasis, spurs the search for new drugs and drug targets. Inhibitors of
human cyclic nucleotide phosphodiesterases (huPDEs), including PDE4, are under
development as novel drugs to treat a range of chronic indications including
asthma, chronic obstructive pulmonary disease and Alzheimer's disease. One class
of huPDE4 inhibitors that has yielded marketed drugs is the benzoxaboroles
(Anacor Pharmaceuticals). METHODOLOGY/PRINCIPAL FINDINGS: A phenotypic screen
involving Schistosoma mansoni and 1,085 benzoxaboroles identified a subset of
huPDE4 inhibitors that induced parasite hypermotility and degeneration. To
uncover the putative schistosome PDE4 target, we characterized four PDE4
sequences (SmPDE4A-D) in the parasite's genome and transcriptome, and cloned and
recombinantly expressed the catalytic domain of SmPDE4A. Among a set of
benzoxaboroles and catechol inhibitors that differentially inhibit huPDE4, a
relationship between the inhibition of SmPDE4A, and parasite hypermotility and
degeneration, was measured. To validate SmPDE4A as the benzoxaborole molecular
target, we first generated Caenorhabditis elegans lines that express a cDNA for
smpde4a on a pde4(ce268) mutant (hypermotile) background: the smpde4a transgene
restored mutant worm motility to that of the wild type. We then showed that
benzoxaborole inhibitors of SmPDE4A that induce hypermotility in the schistosome
also elicit a hypermotile response in the C. elegans lines that express the
smpde4a transgene, thereby confirming SmPDE4A as the relevant target.
CONCLUSIONS/SIGNIFICANCE: The orthogonal chemical, biological and genetic
strategies employed identify SmPDE4A's contribution to parasite motility and
degeneration, and its potential as a drug target. Transgenic C. elegans is
highlighted as a potential screening tool to optimize small molecule chemistries
to flatworm molecular drug targets.
PMID- 28704397
TI - Impact of Sjogren's syndrome on Parkinson's disease: A nationwide case-control
study.
AB - OBJECTIVE: To investigate whether Sjogren's syndrome would have an influence on
the development of Parkinson's disease. METHODS: A population-based case-control
study was conducted. Participants consisted of 7716 subjects with newly diagnosed
Parkinson's disease and a population of 75129 matched control subjects between
2000 and 2010. We measured the risk of Parkinson's disease in association with
Sjogren's syndrome by using adjusted odds ratios. RESULTS: A total of 143
Parkinson's disease subjects (1.9%) and 893 control subjects (1.2%) suffered from
Sjogren's syndrome (p < 0.001). The crude odds ratio for Parkinson's disease
among subjects with Sjogren's syndrome was 1.56 (95% CI 1.30-1.86; p < 0.01).
After adjustment for potential confounders which have been proposed that would
increase the risk of development of Parkinson's disease, Sjogren's syndrome was
found to be significantly associated with the risk of Parkinson's disease with an
odds ratio of 1.37 (95% CI 1.15-1.65; p < 0.01). CONCLUSION: This study
preliminarily proposed that Sjogren's syndrome was significant associated with an
increased risk of Parkinson's disease.
PMID- 28704398
TI - Temporal dynamics of neurogenomic plasticity in response to social interactions
in male threespined sticklebacks.
AB - Animals exhibit dramatic immediate behavioral plasticity in response to social
interactions, and brief social interactions can shape the future social
landscape. However, the molecular mechanisms contributing to behavioral
plasticity are unclear. Here, we show that the genome dynamically responds to
social interactions with multiple waves of transcription associated with distinct
molecular functions in the brain of male threespined sticklebacks, a species
famous for its behavioral repertoire and evolution. Some biological functions
(e.g., hormone activity) peaked soon after a brief territorial challenge and then
declined, while others (e.g., immune response) peaked hours afterwards. We
identify transcription factors that are predicted to coordinate waves of
transcription associated with different components of behavioral plasticity.
Next, using H3K27Ac as a marker of chromatin accessibility, we show that a brief
territorial intrusion was sufficient to cause rapid and dramatic changes in the
epigenome. Finally, we integrate the time course brain gene expression data with
a transcriptional regulatory network, and link gene expression to changes in
chromatin accessibility. This study reveals rapid and dramatic epigenomic
plasticity in response to a brief, highly consequential social interaction.
PMID- 28704399
TI - Cooperative stochastic binding and unbinding explain synaptic size dynamics and
statistics.
AB - Synapses are dynamic molecular assemblies whose sizes fluctuate significantly
over time-scales of hours and days. In the current study, we examined the
possibility that the spontaneous microscopic dynamics exhibited by synaptic
molecules can explain the macroscopic size fluctuations of individual synapses
and the statistical properties of synaptic populations. We present a mesoscopic
model, which ties the two levels. Its basic premise is that synaptic size
fluctuations reflect cooperative assimilation and removal of molecules at a patch
of postsynaptic membrane. The introduction of cooperativity to both assimilation
and removal in a stochastic biophysical model of these processes, gives rise to
features qualitatively similar to those measured experimentally: nanoclusters of
synaptic scaffolds, fluctuations in synaptic sizes, skewed, stable size
distributions and their scaling in response to perturbations. Our model thus
points to the potentially fundamental role of cooperativity in dictating synaptic
remodeling dynamics and offers a conceptual understanding of these dynamics in
terms of central microscopic features and processes.
PMID- 28704400
TI - Genome-wide analysis of the CCCH zinc finger family identifies tissue specific
and stress responsive candidates in chickpea (Cicer arietinum L.).
AB - The CCCH zinc finger is a group of proteins characterised by a typical motif
consisting of three cysteine residues and one histidine residue. These proteins
have been reported to play important roles in regulation of plant growth,
developmental processes and environmental responses. In the present study, genome
wide analysis of the CCCH zinc finger gene family was carried out in the
available chickpea genome. Various bioinformatics tools were employed to predict
58 CCCH zinc finger genes in chickpea (designated CarC3H1-58), which were
analysed for their physio-chemical properties. Phylogenetic analysis classified
the proteins into 12 groups in which members of a particular group had similar
structural organization. Further, the numbers as well as the types of CCCH motifs
present in the CarC3H proteins were compared with those from Arabidopsis and
Medicago truncatula. Synteny analysis revealed valuable information regarding the
evolution of this gene family. Tandem and segmental duplication events were
identified and their Ka/Ks values revealed that the CarC3H gene family in
chickpea had undergone purifying selection. Digital, as well as real time qRT-PCR
expression analysis was performed which helped in identification of several
CarC3H members that expressed preferentially in specific chickpea tissues as well
as during abiotic stresses (desiccation, cold, salinity). Moreover, molecular
characterization of an important member CarC3H45 was carried out. This study
provides comprehensive genomic information about the important CCCH zinc finger
gene family in chickpea. The identified tissue specific and abiotic stress
specific CCCH genes could be potential candidates for further characterization to
delineate their functional roles in development and stress.
PMID- 28704401
TI - IL-13 is a central mediator of chemical-induced airway hyperreactivity in mice.
AB - BACKGROUND: While the importance of the Th2 cytokine IL-13 as a central mediator
of airway hyperreactivity (AHR) has been described in allergic protein-induced
asthma, this has never been investigated in chemical-induced asthma. OBJECTIVE:
We examined the importance of IL-13 in a mouse model of chemical-induced AHR,
using toluene-2,4-diisocyanate (TDI). METHODS: In a first set-up, wild type (WT)
and IL-13 knockout (KO) C57Bl/6 mice were dermally treated on days 1 and 8 with
1% TDI or vehicle (acetone/olive oil) on both ears. On day 15, mice received an
intranasal instillation with 0.1% TDI or vehicle. In a second set-up, WT mice
sensitized with 1% TDI or vehicle, received i.v. either anti-IL-13 or control
antibody prior to the intranasal challenge. RESULTS: TDI-sensitized and TDI
challenged WT mice showed AHR to methacholine, in contrast to TDI-sensitized and
TDI-challenged IL-13 KO mice, which also showed lower levels of total serum IgE.
TDI-sensitized and TDI-challenged IL-13 KO mice had lower numbers of T-cells in
the auricular lymph nodes. TDI-treated WT mice, receiving anti-IL-13, showed no
AHR, in contrast to those receiving control antibody, despite increased levels of
IgE. Anti-IL-13 treatment in TDI-treated WT mice resulted in lower levels of
serum IL-13, but did not induce changes in T- and B-cell numbers, and in the
cytokine production profile. CONCLUSION AND CLINICAL RELEVANCE: We conclude that
IL-13 plays a critical role in the effector phase of chemical-induced, immune
mediated AHR. This implicates that anti-IL-13 treatment could have a beneficial
effect in patients with this asthma phenotype.
PMID- 28704402
TI - Are disease reservoirs special? Taxonomic and life history characteristics.
AB - Pathogens that spill over between species cause a significant human and animal
health burden. Here, we describe characteristics of animal reservoirs that are
required for pathogen spillover. We assembled and analyzed a database of 330
disease systems in which a pathogen spills over from a reservoir of one or more
species. Three-quarters of reservoirs included wildlife, and 84% included
mammals. Further, 65% of pathogens depended on a community of reservoir hosts,
rather than a single species, for persistence. Among mammals, the most frequently
identified reservoir hosts were rodents, artiodactyls, and carnivores. The
distribution among orders of mammalian species identified as reservoirs did not
differ from that expected by chance. Among disease systems with high priority
pathogens and epidemic potential, we found birds, primates, and bats to be
overrepresented. We also analyzed the life history traits of mammalian reservoir
hosts and compared them to mammals as a whole. Reservoir species had faster life
history characteristics than mammals overall, exhibiting traits associated with
greater reproductive output rather than long-term survival. Thus, we find that in
many respects, reservoirs of spillover pathogens are indeed special. The
described patterns provide a useful resource for studying and managing emerging
infectious diseases.
PMID- 28704403
TI - Genetic variants of PTGS2, TXA2R and TXAS1 are associated with carotid plaque
vulnerability, platelet activation and TXA2 levels in ischemic stroke patients.
AB - Eicosanoids may play a role in ischemic stroke. However, the associations of
variants in cyclooxygenase (COX) pathway genes and interaction among these
variants with carotid plaque vulnerability are not fully understood. In present
study, twelve variants in COX pathway genes were examined using matrix-assisted
laser desorption ionization time-of-flight mass spectrometry method in 396
patients with ischemic stroke and 291 controls. Platelet aggregation, platelet
leukocyte aggregates, and urine 11-dehydrothromboxane B2 (11-dTxB2) were also
measured. According to the results of carotid high-resolution B-mode ultrasound,
the patients were stratified into the following groups [i.e., non-carotid plaque
and carotid plaque. The carotid plaque was further classified into subgroups of
echolucent plaque (ELP) and echogenic plaque (EGP)]. Additionally, gene-gene
interactions were analyzed to assess whether there was any interactive role for
assessed variants in affecting carotid plaque vulnerability, platelet activation
and 11-dTxB2 levels. There were no significant differences in the frequencies of
genotypes of the twelve variants between patients and controls. Among 396
patients, 294 cases (74.2%) had carotid plaques (106 had ELP, 188 had EGP).
Frequency of PTGS2 rs20417CC, TXAS1 rs2267679TT, TXAS1 rs41708TT, PTGIS rs5602CC,
and TXA2R rs1131882TT genotype was significantly higher in patients with plaque
compared with patients without plaque, or in patients with ELP compared with
patients with EGP. 11-dTxB2 levels, platelet aggregation and platelet-leukocyte
aggregates were significantly higher in patients with ELP compared with patients
without plaque or with EGP. Multivariate logistic regression analysis revealed
that PTGS2 rs20417CC, TXA2R rs1131882TT, and high-risk interaction among variants
in PTGS2 rs20417, TXA2R rs1131882 and TXAS1 rs41708 were independently associated
with the risk of ELP after adjusting for confounding variables. The variants in
COX pathway genes and the high-risk interactions among variants in PTGS2 rs20417,
TXA2R rs1131882 and TXAS1 rs41708 were associated with high 11-dTxB2 and platelet
activation, and independently associated with the risk of carotid plaque
vulnerability. These variants might be potential markers for plaque instability.
PMID- 28704404
TI - PA21, a novel phosphate binder, improves renal osteodystrophy in rats with
chronic renal failure.
AB - The effects of PA21, a novel iron-based and non-calcium-based phosphate binder,
on hyperphosphatemia and its accompanying bone abnormality in chronic kidney
disease-mineral and bone disorder (CKD-MBD) were evaluated. Rats with adenine
induced chronic renal failure (CRF) were prepared by feeding them an adenine
containing diet for four weeks. They were also freely fed a diet that contained
PA21 (0.5, 1.5, and 5%), sevelamer hydrochloride (0.6 and 2%) or lanthanum
carbonate hydrate (0.6 and 2%) for four weeks. Blood biochemical parameters were
measured and bone histomorphometry was performed for femurs, which were isolated
after drug treatment. Serum phosphorus and parathyroid hormone (PTH) levels were
higher in the CRF rats. Administration of phosphate binders for four weeks
decreased serum phosphorus and PTH levels in a dose-dependent manner and there
were significant decreases in the AUC0-28 day of these parameters in 5% PA21, 2%
sevelamer hydrochloride, and 2% lanthanum carbonate hydrate groups compared with
that in the CRF control group. Moreover, osteoid volume improved significantly in
5% of the PA21 group, and fibrosis volume and cortical porosity were ameliorated
in 5% PA21, 2% sevelamer hydrochloride, and 2% lanthanum carbonate hydrate
groups. These results suggest that PA21 is effective against hyperphosphatemia,
secondary hyperparathyroidism, and bone abnormalities in CKD-MBD as sevelamer
hydrochloride and lanthanum carbonate hydrate are, and that PA21 is a new
potential alternative to phosphate binders.
PMID- 28704405
TI - Community health workers for non-communicable diseases prevention and control in
developing countries: Evidence and implications.
AB - BACKGROUND: National programs for non-communicable diseases (NCD) prevention and
control in different low middle income countries have a strong community
component. A community health worker (CHW) delivers NCD preventive services using
informational as well as behavioural approaches. Community education and
interpersonal communication on lifestyle modifications is imparted with focus on
primordial prevention of NCDs and screening is conducted as part of early
diagnosis and management. However, the effectiveness of health promotion and
screening interventions delivered through community health workers needs to be
established. OBJECTIVE: This review synthesised evidence on effectiveness of CHW
delivered NCD primary prevention interventions in low and middle-income countries
(LMICs). METHODS: A systematic review of trials that utilised community health
workers for primary prevention/ early detection strategy in the management of
NCDs (Diabetes, cardiovascular diseases (CVD), cancers, stroke, Chronic
Obstructive Pulmonary Diseases (COPD)) in LMICs was conducted. Digital databases
like PubMed, EMBASE, OVID, Cochrane library, dissertation abstracts, clinical
trials registry web sites of different LMIC were searched for such publications
between years 2000 and 2015. We focussed on community based randomised controlled
trial and cluster randomised trials without any publication language limitation.
The primary outcome of review was percentage change in population with different
behavioural risk factors. Additionally, mean overall changes in levels of several
physical or biochemical parameters were studied as secondary outcomes. Subgroup
analyses was performed by the age and sex of participants, and sensitivity
analyses was conducted to assess the robustness of the findings. RESULTS: Sixteen
trials meeting the inclusion criteria were included in the review. Duration,
study populations and content of interventions varied across trials. The duration
of the studies ranged from mean follow up of 4 months for some risk factors to 19
months, and primary responsibilities of health workers included health promotion,
treatment adherence and follow ups. Only a single trial reported all-cause
mortality. The pooled effect computed indicated an increase in tobacco cessation
(RR: 2.0, 95%CI: 1.11, 3.58, moderate-quality evidence) and a decrease in
systolic blood pressure ((MD: -4.80, 95% CI: -8.12, -1.49, I2 = 93%, very low
quality evidence), diastolic blood pressure ((MD: -2.88, 95% CI: -5.65, -0.10, I2
= 96%, very low-quality evidence)) and blood sugar levels (glycated haemoglobin
MD: -0.83%, 95%CI: -1.25,-0.41). None of the included trials reported on adverse
events. CONCLUSIONS: Evidence on the implementation of primary prevention
strategies using community health workers is still developing. Existing evidence
suggests that, compared with standard care, using CHWs in health programmes have
the potential to be effective in LMICs, particularly for tobacco cessation, blood
pressure and diabetes control.
PMID- 28704406
TI - FTIR spectroscopy of whole cells for the monitoring of yeast apoptosis mediated
by p53 over-expression and its suppression by Nigella sativa extracts.
AB - p53 over expression in yeast results in cell death with typical markers of
apoptosis such as DNA fragmentation and phosphatidylserine externalization. We
aimed to substitute/supplement classical fluorescent techniques (TUNEL, Annexin
V, ROS detection) usually used to detect biochemical changes occurring during
yeast apoptosis mediated by p53 over expression and the effect of anti-apoptotic
purified molecules from Nigel (Nigella sativa) extracts on these same yeasts by
the label free technique of FTIR spectroscopy. The comparison of the entire IR
spectra highlighted clear modifications between apoptotic p53-expressing yeasts
and normal ones. More precisely, DNA damage was detected by the decrease of band
intensities at 1079 and 1048 cm-1. While phosphatidylserine exposure was followed
by the increase of nusCH2 and nuasCH2 bands of unsaturated fatty acids that were
exhibited at 2855 and 2926 cm-1, and the appearance of the C = O ester functional
group band at 1740 cm-1. In a second step, this FTIR approach was used to
estimate the effect of a purified fraction of the Nigel extract. The modulation
of band intensities specific to DNA and membrane status was in agreement with
apoptosis supression in presence of the Nigel extracts. FTIR spectroscopy is thus
proven to be a very reliable technique to monitor the apoptotic cell death in
yeast and to be used as a means of evaluating the biomolecules effect on yeast
survival.
PMID- 28704407
TI - Variations in achievement of evidence-based, high-impact quality indicators in
general practice: An observational study.
AB - BACKGROUND: There are widely recognised variations in the delivery and outcomes
of healthcare but an incomplete understanding of their causes. There is a growing
interest in using routinely collected 'big data' in the evaluation of healthcare.
We developed a set of evidence-based 'high impact' quality indicators (QIs) for
primary care and examined variations in achievement of these indicators using
routinely collected data in the United Kingdom (UK). METHODS: Cross-sectional
analysis of routinely collected, electronic primary care data from a sample of
general practices in West Yorkshire, UK (n = 89). The QIs covered aspects of care
(including processes and intermediate clinical outcomes) in relation to diabetes,
hypertension, atrial fibrillation, myocardial infarction, chronic kidney disease
(CKD) and 'risky' prescribing combinations. Regression models explored the impact
of practice and patient characteristics. Clustering within practice was accounted
for by including a random intercept for practice. RESULTS: Median practice
achievement of the QIs ranged from 43.2% (diabetes control) to 72.2% (blood
pressure control in CKD). Considerable between-practice variation existed for all
indicators: the difference between the highest and lowest performing practices
was 26.3 percentage points for risky prescribing and 100 percentage points for
anticoagulation in atrial fibrillation. Odds ratios associated with the random
effects for practices emphasised this; there was a greater than ten-fold
difference in the likelihood of achieving the hypertension indicator between the
lowest and highest performing practices. Patient characteristics, in particular
age, gender and comorbidity, were consistently but modestly associated with
indicator achievement. Statistically significant practice characteristics were
identified less frequently in adjusted models. CONCLUSIONS: Despite various
policy and improvement initiatives, there are enduring inappropriate variations
in the delivery of evidence-based care. Much of this variation is not explained
by routinely collected patient or practice variables, and is likely to be
attributable to differences in clinical and organisational behaviour.
PMID- 28704408
TI - The Lazarillo's game: Sharing resources with asymmetric conditions.
AB - The Lazarillo of Tormes' picaresque novel introduces a story where two subjects
sequentially extract (one, two or three) tokens from a common pool in an
asymmetric information framework (the first player cannot observe her partners'
actions). By introducing a reward for both subjects in case that in every period
at least one subject had taken one single token, we define an interesting
coordination game. We conduct an experiment with 120 undergraduate students to
study their behavior in this framework. We find that if the second player is
allowed to take more tokens than her partner, then the frequency of cooperators
does not seem to be affected by the informational asymmetry. Nevertheless, this
asymmetry (i) incentives the second player to use her 'power of extraction' while
the social externality is still available, (ii) yields to more asymmetric profit
distributions when subjects win the social externality and (iii) delays the
breach period in case of coordination failure. Furthermore, the first choice of
the first player is determinant for getting the reward.
PMID- 28704409
TI - Soluble activin type IIB receptor improves fracture healing in a closed tibial
fracture mouse model.
AB - Fractures still present a significant burden to patients due to pain and periods
of unproductivity. Numerous growth factors have been identified to regulate bone
remodeling. However, to date, only the bone morphogenetic proteins (BMPs) are
used to enhance fracture healing in clinical settings. Activins are pleiotropic
growth factors belonging to the TGF-beta superfamily. We and others have recently
shown that treatment with recombinant fusion proteins of activin receptors
greatly increases bone mass in different animal models by trapping activins and
other ligands thus inhibiting their signaling pathways. However, their effects on
fracture healing are less known. Twelve-week old male C57Bl mice were subjected
to a standardized, closed tibial fracture model. Animals were divided into
control and treatment groups and were administered either PBS control or a
soluble activin type IIB receptor (ActRIIB-Fc) intraperitoneally once a week for
a duration of two or four weeks. There were no significant differences between
the groups at two weeks but we observed a significant increase in callus
mineralization in ActRIIB-Fc-treated animals by microcomputed tomography imaging
at four weeks. Bone volume per tissue volume was 60%, trabecular number 55% and
bone mineral density 60% higher in the 4-week calluses of the ActRIIB-Fc-treated
mice (p<0.05 in all). Biomechanical strength of 4-week calluses was also
significantly improved by ActRIIB-Fc treatment as stiffness increased by 64% and
maximum force by 45% (p<0.05) compared to the PBS-injected controls. These
results demonstrate that ActRIIB-Fc treatment significantly improves healing of
closed long bone fractures. Our findings support the previous reports of activin
receptors increasing bone mass but also demonstrate a novel approach for using
ActRIIB-Fc to enhance fracture healing.
PMID- 28704410
TI - Improving numeracy through values affirmation enhances decision and STEM
outcomes.
AB - Greater numeracy has been correlated with better health and financial outcomes in
past studies, but causal effects in adults are unknown. In a 9-week longitudinal
study, undergraduate students, all taking a psychology statistics course, were
randomly assigned to a control condition or a values-affirmation manipulation
intended to improve numeracy. By the final week in the course, the numeracy
intervention (statistics-course enrollment combined with values affirmation)
enhanced objective numeracy, subjective numeracy, and two decision-related
outcomes (financial literacy and health-related behaviors). It also showed
positive indirect-only effects on financial outcomes and a series of STEM-related
outcomes (course grades, intentions to take more math-intensive courses, later
math-intensive courses taken based on academic transcripts). All decision and
STEM-related outcome effects were mediated by the changes in objective and/or
subjective numeracy and demonstrated similar and robust enhancements.
Improvements to abstract numeric reasoning can improve everyday outcomes.
PMID- 28704411
TI - Complete factorial design to adjust pH and sugar concentrations in the inoculum
phase of Ralstonia solanacearum to optimize P(3HB) production.
AB - Poly(3-hydroxybutyrate) (P(3HB)) is a biodegradable plastic biopolymer that
accumulates as lipophilic inclusions in the cytoplasm of some microorganisms. The
biotechnological process by which P(3HB) is synthesized occurs in two phases. The
first phase involves cell growth in a complex culture medium, while the second
phase involves polymer accumulation in the presence of excess carbon sources. As
such, the efficiency of the second phase depends on the first phase. The aim of
this study was to evaluate culture media with different concentrations of sucrose
and glucose and different pH values in the inoculum phase of Ralstonia
solanacearum RS with the intention of identifying methods by which the biomass
yield could be increased, subsequently enhancing the yield of P(3HB). The culture
medium was formulated according to the experimental planning type of central
composite rotational design 22. The independent variables were pH and sugar
concentration (sucrose and glucose), and the dependent variables were OD600nm,
dry cell weight (DCW), and P(3HB) yield. The highest cell growth, estimated by
the OD600nm (20.6) and DCW (5.35) values, was obtained when sucrose was used in
the culture medium at a concentration above 35 g.L-1 in combination with an
acidic pH. High polymer (45%) accumulation was also achieved under these
conditions. Using glucose, the best results for OD600nm (12.5) and DCW (2.74)
were also obtained at acidic pH but with a sugar concentration at the minimum
values evaluated. Due to the significant accumulation of polymer in the cells
that were still in the growth phase, the accumulating microorganism P(3HB)
Ralstonia solanacearum RS can be classified as having type II metabolism in
relation to the polymer accumulation phase, which is different from other
Ralstonia spp. studied until this time.
PMID- 28704412
TI - Synthetic PreImplantation Factor (PIF) prevents fetal loss by modulating LPS
induced inflammatory response.
AB - Maternal control of inflammation is essential during pregnancy and an exaggerated
response is one of the underlying causes of fetal loss. Inflammatory response is
mediated by multiple factors and Toll-like receptors (TLRs) are central.
Activation of TLRs results in NALP-3 mediated assembly of apoptosis-associated
speck-like protein containing a CARD (ASC) and caspase-1 into the inflammasome
and production of pro-inflammatory cytokines IL-1beta and IL-18. Given that
preventing measures are lacking, we investigated PreImplantation Factor (PIF) as
therapeutic option as PIF modulates Inflammation in pregnancy. Additionally,
synthetic PIF (PIF analog) protects against multiple immune disorders. We used a
LPS induced murine model of fetal loss and synthetic PIF reduced this fetal loss
and increased the embryo weight significantly. We detected increased PIF
expression in the placentae after LPS insult. The LPS induced serum and placenta
cytokines were abolished by synthetic PIF treatment and importantly synthetic PIF
modulated key members of inflammasome complex NALP-3, ASC, and caspase-1 as well.
In conclusion our results indicate that synthetic PIF protects against LPS
induced fetal loss, likely through modulation of inflammatory response especially
the inflammasome complex. Given that synthetic PIF is currently tested in
autoimmune diseases of non-pregnant subjects (clinicaltrials.gov, NCT02239562),
therapeutic approach during pregnancy can be envisioned.
PMID- 28704413
TI - Association of insulin resistance with near peak bone mass in the femur and
lumbar spine of Korean adults aged 25-35: The Korean National Health and
Nutrition Examination Survey 2008-2010.
AB - OBJECTIVE: This study aimed to evaluate the relationship between insulin
resistance and the bone mineral density (BMD) of femur and lumbar spine in Korean
adults who are expected to exhibit near peak bone mass. METHODS: Data from the
Korean National Health and Nutrition Examination Survey 2008-2010 were analyzed.
A total of 2,750 participants aged 25-35 years were included. Insulin resistance
was assessed using a homeostatic model assessment of insulin resistance (HOMA-IR)
and serum fasting insulin. RESULTS: In a multivariate linear regression analysis,
the HOMA-IR was significantly inversely associated with the BMD of the total hip
(TH, beta = -0.052, P = 0.002), femoral neck (FN, beta = -0.072, P<0.001),
femoral trochanter (FTr, beta = -0.055, P = 0.003), femoral intertrochanter
(FITr, beta = -0.041, P = 0.015), and lumbar spine (LS, beta = -0.063, P = 0.001)
among all study subjects after adjustment for gender, age, height, weight, whole
body fat mass percentage, systolic blood pressure, diastolic blood pressure,
total cholesterol, triglyceride, high-density lipoprotein cholesterol, low
density lipoprotein cholesterol, vitamin D, smoking, alcohol intake, physical
activity, education level, and household income in both genders as well as labor,
the use of oral contraceptives, and age at menarche in females. The serum fasting
insulin was significantly inversely associated with the BMD of the TH (beta =
0.055, P = 0.001), FN (beta = -0.072, P<0.001), FTr (beta = -0.055, P = 0.003),
FITr (beta = -0.045, P = 0.009), and LS (beta = -0.064, P = 0.001) among all
subjects in a multivariate linear regression analysis. CONCLUSION: Our results
suggest that insulin resistance may be independently and inversely associated
with the near peak bone mass of the femur and lumbar spine.
PMID- 28704414
TI - Examining the use of Amazon's Mechanical Turk for edge extraction of the occlusal
surface of fossilized bovid teeth.
AB - In order to reconstruct environments associated with Plio-Pleistocene hominins in
southern Africa, researchers frequently rely upon the animals associated with the
hominins, in particular, animals in the Family Bovidae. Bovids in southern Africa
are typically identified by their teeth. However, identifying the taxon of a
bovid tooth is challenging due to various biasing factors. Furthermore,
inaccurate identification of fossil bovids can have significant consequences on
the reconstructed paleoenvironment. Recent research on the classification of
bovid fossil teeth has relied on using elliptical Fourier analysis to summarize
the shape of the outline of the occlusal surface of the tooth and the resulting
harmonic amplitudes. Currently, an expert in the field must manually place
landmarks around the edges of each tooth which is slow and time consuming. This
study tests whether it is possible to crowdsource this task, while maintaining
the necessary level of quality needed to perform a statistical analysis on each
tooth. Amazon Mechanical Turk workers place landmarks on the edge of the tooth
which is compared to the performance of an expert in the field. The results
suggest that crowdsourcing the digitization process is reliable and replicable.
With the technical aspects of digitization managed, researchers can concentrate
on analyzing and interpreting the data.
PMID- 28704415
TI - C. elegans SMA-10 regulates BMP receptor trafficking.
AB - Signal transduction of the conserved transforming growth factor-beta (TGFbeta)
family signaling pathway functions through two distinct serine/threonine
transmembrane receptors, the type I and type II receptors. Endocytosis
orchestrates the assembly of signaling complexes by coordinating the entry of
receptors with their downstream signaling mediators. Recently, we showed that the
C. elegans type I bone morphogenetic protein (BMP) receptor SMA-6, part of the
TGFbeta family, is recycled through the retromer complex while the type II
receptor, DAF-4 is recycled in a retromer-independent, ARF-6 dependent manner.
From genetic screens in C. elegans aimed at identifying new modifiers of BMP
signaling, we reported on SMA-10, a conserved LRIG (leucine-rich and
immunoglobulin-like domains) transmembrane protein. It is a positive regulator of
BMP signaling that binds to the SMA-6 receptor. Here we show that the loss of sma
10 leads to aberrant endocytic trafficking of SMA-6, resulting in its
accumulation in distinct intracellular endosomes including the early endosome,
multivesicular bodies (MVB), and the late endosome with a reduction in signaling
strength. Our studies show that trafficking defects caused by the loss of sma-10
are not universal, but affect only a limited set of receptors. Likewise, in
Drosophila, we find that the fly homolog of sma-10, lambik (lbk), reduces
signaling strength of the BMP pathway, consistent with its function in C. elegans
and suggesting evolutionary conservation of function. Loss of sma-10 results in
reduced ubiquitination of the type I receptor SMA-6, suggesting a possible
mechanism for its regulation of BMP signaling.
PMID- 28704416
TI - Genetic variation in the eicosanoid pathway is associated with non-small-cell
lung cancer (NSCLC) survival.
AB - Globally, lung cancer results in more deaths worldwide than any other cancer,
indicating a need for better treatments. Members of the eicosanoid metabolism
pathway represent promising therapeutic targets, as several enzymes involved in
the generation of these lipids are dysregulated in many cancers and their
inhibition reduces lung cancer growth in mouse models. However, genetic variation
of enzymes involved in eicosanoid metabolism has not been adequately examined for
association with lung cancer. The goal of this study was to determine whether
germline genetic variation altering eicosanoid producing enzyme function and/or
expression are associated with differences in lung cancer survival. We examined
the association of genetic variation with mortality within eicosanoid metabolism
genes in 395 non-small-cell lung cancer (NSCLC) cases from the Southern Community
Cohort Study (SCCS). A total of 108 SNPs, both common and rare, in 19 genes, were
examined for association. No common or rare variants were associated with lung
cancer survival across the entire study population. However, rare variants in
ALOX15B (arachidonate 15-lipoxygenase, type B) and the common variant rs12529 in
AKR1C3 (prostaglandin F synthase) were associated with NSCLC mortality in women
and African Americans, respectively. Rare variants in ALOX15B were associated
with greater mortality in women (HR = 2.10, 95% CI = 1.25-3.54, p-value = 0.005).
The major allele of rs12529 in AKCR1C3 associated with improved survival in
African Americans (HR = 0.74, 95% CI = 0.59-0.92, p-value = 0.008). The lack of
genetic associations among all NSCLC cases and the association among women only
for rare variants in ALOX15B may, in part, explain the better NSCLC survival
observed among women. These results raise the possibility that some subgroups
within the NSCLC population may benefit from drugs targeting eicosanoid
metabolism.
PMID- 28704417
TI - Bayesian spatio-temporal modeling of mortality in relation to malaria incidence
in Western Kenya.
AB - INTRODUCTION: The effect of malaria exposure on mortality using health facility
incidence data as a measure of transmission has not been well investigated.
Health and demographic surveillance systems (HDSS) routinely capture data on
mortality, interventions and other household related indicators, offering a
unique platform for estimating and monitoring the incidence-mortality
relationship in space and time. METHODS: Mortality data from the HDSS located in
Western Kenya collected from 2007 to 2012 and linked to health facility incidence
data were analysed using Bayesian spatio-temporal survival models to investigate
the relation between mortality (all-cause/malaria-specific) and malaria incidence
across all age groups. The analysis adjusted for insecticide-treated net (ITN)
ownership, socio-economic status (SES), distance to health facilities and
altitude. The estimates obtained were used to quantify excess mortality due to
malaria exposure. RESULTS: Our models identified a strong positive relationship
between slide positivity rate (SPR) and all-cause mortality in young children 1-4
years (HR = 4.29; 95% CI: 2.78-13.29) and all ages combined (HR = 1.55; 1.04
2.80). SPR had a strong positive association with malaria-specific mortality in
young children (HR = 9.48; 5.11-37.94), however, in older children (5-14 years),
it was associated with a reduction in malaria specific mortality (HR = 0.02;
0.003-0.33). CONCLUSION: SPR as a measure of transmission captures well the
association between malaria transmission intensity and all-cause/malaria
mortality. This offers a quick and efficient way to monitor malaria burden.
Excess mortality estimates indicate that small changes in malaria incidence
substantially reduce overall and malaria specific mortality.
PMID- 28704418
TI - The collalphagen III fibril has a "flexi-rod" structure of flexible sequences
interspersed with rigid bioactive domains including two with hemostatic roles.
AB - Collagen III is critical to the integrity of blood vessels and distensible
organs, and in hemostasis. Examination of the human collagen III interactome
reveals a nearly identical structural arrangement and charge distribution pattern
as for collagen I, with cell interaction domains, fibrillogenesis and enzyme
cleavage domains, several major ligand-binding regions, and intermolecular
crosslink sites at the same sites. These similarities allow heterotypic fibril
formation with, and substitution by, collagen I in embryonic development and
wound healing. The collagen III fibril assumes a "flexi-rod" structure with
flexible zones interspersed with rod-like domains, which is consistent with the
molecule's prominence in young, pliable tissues and distensible organs. Collagen
III has two major hemostasis domains, with binding motifs for von Willebrand
factor, alpha2beta1 integrin, platelet binding octapeptide and glycoprotein VI,
consistent with the bleeding tendency observed with COL3A1 disease-causing
sequence variants.
PMID- 28704419
TI - A pilot feeding study for adults with asthma: The healthy eating better breathing
trial.
AB - RATIONALE: Evidence from observational studies and to a lesser extent clinical
trials suggest that a healthy diet may improve symptoms and lung function in
patients with asthma. We conducted a pilot study to determine the feasibility of
conducting a larger scale dietary trial and to provide preliminary evidence on
the impact of a healthy diet on asthma outcomes. METHODS: In a randomized, two
period cross-over trial, participants with asthma received a 4-week dietary
intervention followed by a usual diet (or vice versa), separated by a 4-week
washout. The dietary intervention was a healthy diet rich in unsaturated fat.
During the dietary intervention, participants ate three meals per week on site at
the Johns Hopkins ProHealth Research Center. All remaining meals and snacks were
provided for participants to consume off-site. During the control diet,
participants were instructed to continue their usual dietary intake. Relevant
biomarkers and asthma clinical outcomes were assessed at 0, 2, and 4 weeks after
starting each arm of the study. RESULTS: Eleven participants were randomized, and
seven completed the full study protocol. Among these seven participants, average
age was 42 years, six were female, and six were African American. Participant
self-report of dietary intake revealed significant increases in fruit, vegetable,
and omega-3 fatty acid intake with the dietary intervention compared to usual
diet. Serum carotenoids (eg. lutein and beta-cryptoxanthin) increased in the
intervention versus control. Total cholesterol decreased in the intervention
versus control diet. There was no consistent effect on asthma outcomes.
CONCLUSIONS: The findings suggest that a feeding trial in participants with
asthma is feasible. Larger trials are needed to definitively assess the potential
benefits of dietary interventions on pulmonary symptoms and function in patients
with asthma.
PMID- 28704420
TI - Relation between high levels of myeloperoxidase in the culprit artery and
microvascular obstruction, infarct size and reverse remodeling in ST-elevation
myocardial infarction.
AB - MAIN OBJECTIVE: To better understand the role of myeloperoxidases (MPO) in
microvascular obstruction (MO) phenomenon and infarct size (IS) using cardiac
magnetic resonance (CMR) data in patients with acute myocardial infarction (AMI).
METHOD: 40 consecutive patients classified according to the median level of MPO
in the culprit artery. A CMR study was performed during the week following AMI
and at 6 months, with late gadolinium enhancement sequences. RESULTS: Persistent
MO was observed in the same proportion (50 vs. 65%, p = 0.728) between the low
vs. high MPO group levels. However, the extent of the microvascular obstruction
was significantly greater in the high-MPO group (6 (0-9) vs.16.5 (0-31), p =
0.027), together with a greater infarct size, and a trend towards a lower left
ventricular ejection fraction (LVEF) (p = 0.054) at one week. CMR data at 6
months showed that reverse systolic remodeling was two fold more present in the
low-MPO group (p = 0.058). Interestingly, the extent of MO (8.5 (6.5-31) vs. 4.1
(3-11.55), p = 0.042) and IS remained significantly greater (24.5 (9.75-35) vs.
7.5 (2.5-18.75), p = 0.022) in the high-MPO group. Moreover, MPO in the culprit
artery appeared to correlate positively with MPO in non-culprit arteries and
serum, and with troponin levels and peak CK. CONCLUSION: This patient-based study
revealed in patients after AMI that high MPO levels in the culprit artery were
associated with more severe microvascular obstruction and greater IS. These
findings may provide new insights pathophysiology explanation for the adverse
prognostic impact of MO.
PMID- 28704421
TI - Transcriptional role of androgen receptor in the expression of long non-coding
RNA Sox2OT in neurogenesis.
AB - The complex architecture of adult brain derives from tightly regulated migration
and differentiation of precursor cells generated during embryonic neurogenesis.
Changes at transcriptional level of genes that regulate migration and
differentiation may lead to neurodevelopmental disorders. Androgen receptor (AR)
is a transcription factor that is already expressed during early embryonic days.
However, AR role in the regulation of gene expression at early embryonic stage is
yet to be determinate. Long non-coding RNA (lncRNA) Sox2 overlapping transcript
(Sox2OT) plays a crucial role in gene expression control during development but
its transcriptional regulation is still to be clearly defined. Here, using
Bicalutamide in order to pharmacologically inactivated AR, we investigated
whether AR participates in the regulation of the transcription of the
lncRNASox2OTat early embryonic stage. We identified a new DNA binding region
upstream of Sox2 locus containing three androgen response elements (ARE), and
found that AR binds such a sequence in embryonic neural stem cells and in mouse
embryonic brain. Our data suggest that through this binding, AR can promote the
RNA polymerase II dependent transcription of Sox2OT. Our findings also suggest
that AR participates in embryonic neurogenesis through transcriptional control of
the long non-coding RNA Sox2OT.
PMID- 28704422
TI - Different relationship of magnocellular-dorsal function and reading-related
skills between Chinese developing and skilled readers.
AB - Previous studies have indicated that the relationship between magnocellular
dorsal (M-D) function and reading-related skills may vary with reading
development in readers of alphabetic languages. Since this relationship could be
affected by the orthographic depth of writing systems, the present study explored
the relationship between M-D function and reading-related skills in Chinese, a
writing system with a deeper orthography than alphabetic languages. Thirty-seven
primary school students and fifty-one undergraduate students participated.
Orthographic and phonological awareness tests were adopted as reading-related
skill measurements. A steady-pedestal paradigm was used to assess the low-spatial
frequency contrast thresholds of M-D function. Results showed that M-D function
was only correlated with orthographic awareness for adults, revealing an
enhancement with reading development; while being related to phonological
awareness only for children revealing a developmental decrement. It suggested
that the mechanism responsible for the relationship between M-D activity and
reading-related skills was affected by the characteristics of literacy
development in Chinese.
PMID- 28704423
TI - Application of near-infrared hyperspectral imaging to discriminate different
geographical origins of Chinese wolfberries.
AB - Near-infrared (874-1734 nm) hyperspectral imaging (NIR-HSI) technique combined
with chemometric methods was used to trace origins of 1200 Chinese wolfberry
samples, which from Ningxia, Inner Mongolia, Sinkiang and Qinghai in China. Two
approaches, named pixel-wise and object-wise, were investigated to discriminative
the origin of these Chinese wolfberries. The pixel-wise classification assigned a
class to each pixel from individual Chinese wolfberries, and with this approach,
the differences in the Chinese wolfberries from four origins were reflected
intuitively. Object-wise classification was performed using mean spectra. The
average spectral information of all pixels of each sample in the hyperspectral
image was extracted as the representative spectrum of a sample, and then
discriminant analysis models of the origins of Chinese wolfberries were
established based on these average spectra. Specifically, the spectral curves of
all samples were collected, and after removal of obvious noise, the spectra of
972-1609 nm were viewed as the spectra of wolfberry. Then, the spectral curves
were pretreated with moving average smoothing (MA), and discriminant analysis
models including support vector machine (SVM), neural network with radial basis
function (NN-RBF) and extreme learning machine (ELM) were established based on
the full-band spectra, the extracted characteristic wavelengths from loadings of
principal component analysis (PCA) and 2nd derivative spectra, respectively.
Among these models, the recognition accuracies of the calibration set and
prediction set of the ELM model based on extracted characteristic wavelengths
from loadings of PCA were higher than 90%. The model not only ensured a high
recognition rate but also simplified the model and was conducive to future rapid
on-line testing. The results revealed that NIR-HSI combined with PCA loadings-ELM
could rapidly trace the origins of Chinese wolfberries.
PMID- 28704424
TI - Examining distinct working memory processes in children and adolescents using
fMRI: Results and validation of a modified Brown-Peterson paradigm.
AB - Verbal working memory (WM) comprises different processes (encoding, maintenance,
retrieval) that are often compromised in brain diseases, but their neural
correlates have not yet been examined in childhood and adolescence. To probe WM
processes and associated neural correlates in developmental samples, and obtain
comparable effects across different ages and populations, we designed an adapted
Brown-Peterson task (verbal encoding and retrieval combined with verbal and
visual concurrent tasks during maintenance) to implement during functional
magnetic resonance imaging (fMRI). In a sample of typically developing children
and adolescents (n = 16), aged 8 to 16 years, our paradigm successfully
identified distinct patterns of activation for encoding, maintenance, and
retrieval. While encoding activated perceptual systems in posterior and ventral
visual regions, retrieval activated fronto-parietal regions associated with
executive control and attention. We found a different impact of verbal versus
visual concurrent processing during WM maintenance: at retrieval, the former
condition evoked greater activations in visual cortex, as opposed to selective
involvement of language-related areas in left temporal cortex in the latter
condition. These results are in accord with WM models, suggesting greater
competition for processing resources when retrieval follows within-domain
compared with cross-domain interference. This pattern was found regardless of
age. Our study provides a novel paradigm to investigate distinct WM brain systems
with reliable results across a wide age range in developmental populations, and
suitable for participants with different WM capacities.
PMID- 28704425
TI - In vitro nuclear magnetic resonance spectroscopy metabolic biomarkers for the
combination of temozolomide with PI3K inhibition in paediatric glioblastoma
cells.
AB - Recent experimental data showed that the PI3K pathway contributes to resistance
to temozolomide (TMZ) in paediatric glioblastoma and that this effect is reversed
by combination treatment of TMZ with a PI3K inhibitor. Our aim is to assess
whether this combination results in metabolic changes that are detectable by
nuclear magnetic resonance (NMR) spectroscopy, potentially providing metabolic
biomarkers for PI3K inhibition and TMZ combination treatment. Using two
genetically distinct paediatric glioblastoma cell lines, SF188 and KNS42, in
vitro 1H-NMR analysis following treatment with the dual pan-Class I PI3K/mTOR
inhibitor PI-103 resulted in a decrease in lactate and phosphocholine (PC) levels
(P<0.02) relative to control. In contrast, treatment with TMZ caused an increase
in glycerolphosphocholine (GPC) levels (P<=0.05). Combination of PI-103 with TMZ
showed metabolic effects of both agents including a decrease in the levels of
lactate and PC (P<0.02) while an increase in GPC (P<0.05). We also report a
decrease in the protein expression levels of HK2, LDHA and CHKA providing likely
mechanisms for the depletion of lactate and PC, respectively. Our results show
that our in vitro NMR-detected changes in lactate and choline metabolites may
have potential as non-invasive biomarkers for monitoring response to combination
of PI3K/mTOR inhibitors with TMZ during clinical trials in children with
glioblastoma, subject to further in vivo validation.
PMID- 28704426
TI - RNA secondary structure and nucleotide composition of the conserved hallmark
sequence of Leishmania SIDER2 retroposons are essential for endonucleolytic
cleavage and mRNA degradation.
AB - We have reported previously that Short Interspersed Degenerate Retroposons of the
SIDER2 subfamily, largely located within 3'UTRs of Leishmania transcripts,
promote rapid turnover of mRNAs through endonucleolytic cleavage within the
highly conserved second tandem 79-nt hallmark sequence (79-nt SII). Here, we used
site-directed mutagenesis and in silico RNA structural studies to delineate the
cis-acting requirements within 79-nt SII for cleavage and mRNA degradation. The
putative cleavage site(s) and other nucleotides predicted to alter the RNA
secondary structure of 79-nt SII were either deleted or mutated and their effect
on mRNA turnover was monitored using a gene reporter system. We found that short
deletions of 8-nt spanning the two predicted cleavage sites block degradation of
SIDER2-containing transcripts, leading to mRNA accumulation. Furthermore, single
or double substitutions of the dinucleotides targeted for cleavage as well as
mutations altering the predicted RNA secondary structure encompassing both
cleavage sites also prevent mRNA degradation, confirming that these dinucleotides
are the bona fide cleavage sites. In line with these results, we show that stage
regulated SIDER2 inactivation correlates with the absence of endonucleolytic
cleavage. Overall, these data demonstrate that both cleavage sites within the
conserved 79-nt SII as well as RNA folding in this region are essential for
SIDER2-mediated mRNA decay, and further support that SIDER2-harboring transcripts
are targeted for degradation by endonucleolytic cleavage.
PMID- 28704427
TI - The influence of human exploration on the microbial community structure and
ammonia oxidizing potential of the Su Bentu limestone cave in Sardinia, Italy.
AB - The bacterial diversity in the Su Bentu Cave in Sardinia was investigated by
means of 16S rRNA gene-based analysis. This 15 km long cave, carved in Jurassic
limestone, hosts a variety of calcite speleothems, and a long succession of
subterranean lakes with mixed granite and carbonate sands. The lower level is
occasionally flooded by a rising groundwater level, but with only scarce input of
organic remains (leaves and charcoal fragments). On the quiet cave pools there
are visible calcite rafts, whereas walls are locally coated with manganese
deposits. In the drier upper levels, where organic input is much more subdued,
moonmilk-a hydrated calcium-magnesium carbonate speleothem-can be found. Relative
humidity approaches 100% and the measured mean annual cave air temperature is
14.8 degrees C. Samples were obtained in 2014 from calcite rafts, moonmilk,
manganese oxide deposits and soil (limestone and granite grains). Microclimatic
conditions in the cave near the sampling sites, sample properties, physico
chemical parameters of water, and sediment composition were determined. The
microbial community of this system is predominately composed of the phyla
Proteobacteria, Actinobacteria, Acidobacteria, Nitrospirae, and Firmicutes.
Sampling sites near the entrance of the cave and in close proximity of the
underground campsite-located 500 meters deep into the cave-revealed the highest
diversity as well as the highest number of human associated microorganisms. Two
samples obtained in very close proximity of each other near the campsite,
indicate that the human impact is localized and is not distributed freely within
the system. Analysis of the abundance of bacterial and archaeal amoA genes
revealed a far greater abundance of archaeal amoA genes compared to bacterial
representatives. The results of this study highlight that human impact is
confined to locations that are utilized as campsites and that exploration leaves
little microbial trails. Furthermore, we uncovered a highly specialized
microbiome, which is perfectly adapted to survive and thrive in an environment
with low nutrient availability.
PMID- 28704428
TI - Kinematic and biomimetic assessment of a hydraulic ankle/foot in level ground and
camber walking.
AB - Improved walking comfort has been linked with better bio-mimicking of the
prosthetic ankle. This study investigated if a hydraulic ankle/foot can provide
enough motion in both the sagittal and frontal planes during level and camber
walking and if the hydraulic ankle/foot better mimics the biological ankle moment
pattern compared with a fixed ankle/foot device. Five active male unilateral
trans-femoral amputees performed level ground walking at normal and fast speeds
and 2.5 degrees camber walking in both directions using their own prostheses
fitted with an "Echelon" hydraulic ankle/foot and an "Esprit" fixed ankle/foot.
Ankle angles and the Trend Symmetry Index of the ankle moments were compared
between prostheses and walking conditions. Significant differences between
prostheses were found in the stance plantarflexion and dorsiflexion peaks with a
greater range of motion being reached with the Echelon foot. The Echelon foot
also showed significantly improved bio-mimicry of the ankle resistance moment in
all walking conditions, either compared with the intact side of the same subject
or with the "normal" mean curve from non-amputees. During camber walking, both
types of ankle/foot devices showed similar changes in the frontal plane ankle
angles. Results from a questionnaire showed the subjects were more satisfied with
Echelon foot.
PMID- 28704429
TI - Effects of coconut oil on glycemia, inflammation, and urogenital microbial
parameters in female Ossabaw mini-pigs.
AB - Forty percent of American women are obese and at risk for type II diabetes,
impaired immune function, and altered microbiome diversity, thus impacting
overall health. We investigated whether obesity induced by an excess calorie,
high fat diet containing hydrogenated fats, fructose, and coconut oil (HFD)
altered glucose homeostasis, peripheral immunity, and urogenital microbial
dynamics. We hypothesized that HFD would cause hyperglycemia, increase peripheral
inflammation, and alter urogenital microbiota to favor bacterial taxonomy
associated with inflammation. We utilized female Ossabaw mini-pigs to model a
'thrifty' metabolic phenotype associated with increased white adipose tissue
mass. Pigs were fed HFD (~4570 kcal/pig/day) or lean (~2000 kcal/pig/day) diet
for a total of 9 estrous cycles (~6 months). To determine the effect of cycle
stage on cytokines and the microbiome, animals had samples collected during
cycles 7 and 9 on certain days of the cycle: D1, 4, 8, 12, 16, 18. Vaginal swabs
or cervical flushes assessed urogenital microbiota. Systemic fatty acids,
insulin, glucose, and cytokines were analyzed. Pig weights and morphometric
measurements were taken weekly. Obese pigs had increased body weight, length,
heart and belly girth but similar glucose concentrations. Obese pigs had
decreased cytokine levels (IL-1beta, TNF-alpha, IL-4, IL-10), arachidonic acid
and plasma insulin, but increased levels of vaccenic acid. Obese pigs had greater
urogenital bacterial diversity, including several taxa known for anti
inflammatory properties. Overall, induction of obesity did not induce
inflammation but shifted the microbial communities within the urogenital tract to
an anti-inflammatory phenotype. We postulate that the coconut oil in the HFD oil
may have supported normal glucose homeostasis and modulated the immune response,
possibly through regulation of microbial community dynamics and fatty acid
metabolism. This animal model holds promise for the study of how different types
of obesity and high fat diets may affect metabolism, immune phenotype, and
microbial dynamics.
PMID- 28704430
TI - Does lack of resources impair access to breast and cervical cancer screening in
Japan?
AB - OBJECTIVES: To assess the impact of the quantity of resources for breast and
cervical cancer screening on the participation rates in screening in clinical
settings in municipalities, as well as to clarify whether lack of resources
impairs access to cancer screening in Japan. METHODS: Of the 1,746 municipalities
in 2010, 1,443 (82.6%) and 1,469 (84.1%) were included in the analyses for breast
and cervical cancer screening, respectively. In order to estimate the effects of
the number of mammography units and of gynecologists on the participation rates
in breast and cervical cancer screening in clinical settings, multiple regression
analyses were performed using the interaction term for urban municipalities.
RESULTS: The average participation rate in screening in clinical settings was
6.01% for breast cancer, and was 8.93% for cervical cancer. The marginal effect
of the number of mammography units per 1,000 women was significantly positive in
urban municipalities (8.20 percent point). The marginal effect of the number of
gynecologists per 1,000 women was significantly positive in all municipalities
(2.54 percent point) and rural municipalities (3.68 percent point). CONCLUSIONS:
Lack of mammography units in urban areas and of gynecologists particularly in
rural areas impaired access to breast and cervical cancer screening. Strategies
are required that quickly improve access for the residents and increase their
participation rates in cancer screening.
PMID- 28704431
TI - Modulation of platelet-derived microparticles to adhesion and motility of human
rheumatoid arthritis fibroblast-like synoviocytes.
AB - Platelet-derived microparticles (PMPs) are closely associated with disease
activity in rheumatoid arthritis (RA) and contribute to the inflammatory process.
Rheumatoid arthritis fibroblast-like synoviocytes (RA-FLSs) play important roles
in the progression of joint destruction. The aim of this study is to demonstrate
whether PMPs affect the adhesion and motility of RA-FLSs. Our data indicated that
PMPs promoted migration, invasion and adhesion to extracellular matrix (ECM) of
RA-FLSs. Further study showed that PMPs up-regulated the expression of matrix
metalloproteinase-1 (MMP1) and increased the level of phosphorylation of NF
kappaB (p-NF-kappaB) and Erk (p-Erk) in RA-FLSs. These results suggest that PMPs
promote RA-FLSs adhesion and motility presumably by increasing MMP1 via
activating Erk-mediated NF-kappaB pathway.
PMID- 28704432
TI - Determination of absolute expression profiles using multiplexed miRNA analysis.
AB - Accurate measurement of miRNA expression is critical to understanding their role
in gene expression as well as their application as disease biomarkers. Correct
identification of changes in miRNA expression rests on reliable normalization to
account for biological and technological variance between samples. Ligo-miR is a
multiplex assay designed to rapidly measure absolute miRNA copy numbers, thus
reducing dependence on biological controls. It uses a simple 2-step ligation
process to generate length coded products that can be quantified using a variety
of DNA sizing methods. We demonstrate Ligo-miR's ability to quantify miRNA
expression down to 20 copies per cell sensitivity, accurately discriminate
between closely related miRNA, and reliably measure differential changes as small
as 1.2-fold. Then, benchmarking studies were performed to show the high
correlation between Ligo-miR, microarray, and TaqMan qRT-PCR. Finally, Ligo-miR
was used to determine copy number profiles in a number of breast, esophageal, and
pancreatic cell lines and to demonstrate the utility of copy number analysis for
providing layered insight into expression profile changes.
PMID- 28704433
TI - Forecasting distributions of an aquatic invasive species (Nitellopsis obtusa)
under future climate scenarios.
AB - Starry stonewort (Nitellopsis obtusa) is an alga that has emerged as an aquatic
invasive species of concern in the United States. Where established, starry
stonewort can interfere with recreational uses of water bodies and potentially
have ecological impacts. Incipient invasion of starry stonewort in Minnesota
provides an opportunity to predict future expansion in order to target early
detection and strategic management. We used ecological niche models to identify
suitable areas for starry stonewort in Minnesota based on global occurrence
records and present-day and future climate conditions. We assessed sensitivity of
forecasts to different parameters, using four emission scenarios (i.e., RCP 2.6,
RCP 4.5, RCP 6, and RCP 8.5) from five future climate models (i.e., CCSM, GISS,
IPSL, MIROC, and MRI). From our niche model analyses, we found that (i)
occurrences from the entire range, instead of occurrences restricted to the
invaded range, provide more informed models; (ii) default settings in Maxent did
not provide the best model; (iii) the model calibration area and its background
samples impact model performance; (iv) model projections to future climate
conditions should be restricted to analogous environments; and (v) forecasts in
future climate conditions should include different future climate models and
model calibration areas to better capture uncertainty in forecasts. Under present
climate, the most suitable areas for starry stonewort are predicted to be found
in central and southeastern Minnesota. In the future, suitable areas for starry
stonewort are predicted to shift in geographic range under some future climate
models and to shrink under others, with most permutations indicating a net
decrease of the species' suitable range. Our suitability maps can serve to design
short-term plans for surveillance and education, while future climate models
suggest a plausible reduction of starry stonewort spread in the long-term if the
trends in climate warming remain.
PMID- 28704434
TI - Urbanization is a main driver for the larval ecology of Aedes mosquitoes in
arbovirus-endemic settings in south-eastern Cote d'Ivoire.
AB - BACKGROUND: Failure in detecting naturally occurring breeding sites of Aedes
mosquitoes can bias the conclusions drawn from field studies, and hence,
negatively affect intervention outcomes. We characterized the habitats of
immature Aedes mosquitoes and explored species dynamics along a rural-to-urban
gradient in a West Africa setting where yellow fever and dengue co-exist.
METHODOLOGY: Between January 2013 and October 2014, we collected immature Aedes
mosquitoes in water containers in rural, suburban, and urban areas of south
eastern Cote d'Ivoire, using standardized sampling procedures. Immature
mosquitoes were reared in the laboratory and adult specimens identified at
species level. PRINCIPAL FINDINGS: We collected 6,159, 14,347, and 22,974 Aedes
mosquitoes belonging to 17, 8, and 3 different species in rural, suburban, and
urban environments, respectively. Ae. aegypti was the predominant species
throughout, with a particularly high abundance in urban areas (99.374%). Eleven
Aedes larval species not previously sampled in similar settings of Cote d'Ivoire
were identified: Ae. albopictus, Ae. angustus, Ae. apicoargenteus, Ae.
argenteopunctatus, Ae. haworthi, Ae. lilii, Ae. longipalpis, Ae. opok, Ae.
palpalis, Ae. stokesi, and Ae. unilineatus. Aedes breeding site positivity was
associated with study area, container type, shade, detritus, water turbidity,
geographic location, season, and the presence of predators. We found
proportionally more positive breeding sites in urban (2,136/3,374, 63.3%),
compared to suburban (1,428/3,069, 46.5%) and rural areas (738/2,423, 30.5%). In
the urban setting, the predominant breeding sites were industrial containers
(e.g., tires and discarded containers). In suburban areas, containers made of
traditional materials (e.g., clay pots) were most frequently encountered. In
rural areas, natural containers (e.g., tree holes and bamboos) were common and
represented 22.1% (163/738) of all Aedes-positive containers, hosting 18.7% of
the Aedes fauna. The predatory mosquito species Culex tigripes was commonly
sampled, while Toxorhynchites and Eretmapodites were mostly collected in rural
areas. CONCLUSIONS/SIGNIFICANCE: In Cote d'Ivoire, urbanization is associated
with high abundance of Aedes larvae and a predominance of artificial containers
as breeding sites, mostly colonized by Ae. aegypti in urban areas. Natural
containers are still common in rural areas harboring several Aedes species and,
therefore, limiting the impact of systematic removal of discarded containers on
the control of arbovirus diseases.
PMID- 28704435
TI - Generation of an artificial human B cell line test system using Transpo-mAbTM
technology to evaluate the therapeutic efficacy of novel antigen-specific fusion
proteins.
AB - The antigen-specific targeting of autoreactive B cells via their unique B cell
receptors (BCRs) is a novel and promising alternative to the systemic suppression
of humoral immunity. We generated and characterized cytolytic fusion proteins
based on an existing immunotoxin comprising tetanus toxoid fragment C (TTC) as
the targeting component and the modified Pseudomonas aeruginosa exotoxin A (ETA')
as the cytotoxic component. The immunotoxin was reconfigured to replace ETA' with
either the granzyme B mutant R201K or MAPTau as human effector domains. The novel
cytolytic fusion proteins were characterized with a recombinant human lymphocytic
cell line developed using Transpo-mAbTM technology. Genes encoding a chimeric TTC
reactive immunoglobulin G were successfully integrated into the genome of the
precursor B cell line REH so that the cells could present TTC-reactive BCRs on
their surface. These cells were used to investigate the specific cytotoxicity of
GrB(R201K)-TTC and TTC-MAPTau, revealing that the serpin proteinase inhibitor 9
resistant granzyme B R201K mutant induced apoptosis specifically in the
lymphocytic cell line. Our data confirm that antigen-based fusion proteins
containing granzyme B (R201K) are suitable candidates for the depletion of
autoreactive B cells.
PMID- 28704436
TI - Platinum nanoparticles induce damage to DNA and inhibit DNA replication.
AB - Sparsely tested group of platinum nanoparticles (PtNPs) may have a comparable
effect as complex platinum compounds. The aim of this study was to observe the
effect of PtNPs in in vitro amplification of DNA fragment of phage lambda, on the
bacterial cultures (Staphylococcus aureus), human foreskin fibroblasts and
erythrocytes. In vitro synthesized PtNPs were characterized by dynamic light
scattering (PtNPs size range 4.8-11.7 nm), zeta potential measurements (-15 mV at
pH 7.4), X-ray fluorescence, UV/vis spectrophotometry and atomic absorption
spectrometry. The PtNPs inhibited the DNA replication and affected the secondary
structure of DNA at higher concentrations, which was confirmed by polymerase
chain reaction, DNA sequencing and DNA denaturation experiments. Further,
cisplatin (CisPt), as traditional chemotherapy agent, was used in all parallel
experiments. Moreover, the encapsulation of PtNPs in liposomes (LipoPtNPs) caused
an approximately 2.4x higher of DNA damage in comparison with CisPt, LipoCisPt
and PtNPs. The encapsulation of PtNPs in liposomes also increased their
antibacterial, cytostatic and cytotoxic effect, which was determined by the
method of growth curves on S. aureus and HFF cells. In addition, both the bare
and encapsulated PtNPs caused lower oxidative stress (determined by GSH/GSSG
ratio) in the human erythrocytes compared to the bare and encapsulated CisPt.
CisPt was used in all parallel experiments as traditional chemotherapy agent.
PMID- 28704437
TI - Impact of environmental microbiota on human microbiota of workers in academic
mouse research facilities: An observational study.
AB - OBJECTIVES: To characterize the microbial environment of workers in academic
mouse research facilities using endotoxin, 16S qPCR, and 16S amplicon sequencing.
To determine whether the work microbiome contributes to the human microbiome of
workers. METHODS: We performed area air sampling from the animal rooms, dirty,
middle, and setup cage wash locations in four academic mouse research facilities.
10 workers in the dirty cage wash area underwent personal air sampling as well as
repeated collection of nasal, oral, and skin samples before and after the work
shift. Environmental samples underwent measurement of endotoxin, mouse allergen,
bacteria copy number via 16S qPCR, and microbial identification via 16S rDNA
sequencing. 16S rDNA sequencing was also performed on human samples before and
after the work shift. SourceTracker was used to identify the contribution of the
work microbiome to the human microbiome. RESULTS: Median endotoxin levels ranged
from undetectable to 1.0 EU/m3. Significant differences in mouse allergen levels,
bacterial copy number, microbial richness, and microbial community structure were
identified between animal, dirty, middle, and setup cage wash locations.
Endotoxin levels had only a moderate correlation with microbial composition.
Location within a facility was a stronger predictor of microbial community
composition (R2 = 0.41, p = 0.002) than facility. The contribution of the work
microbiome to the pre-shift human microbiome of workers was estimated to be 0.1
+/- 0.1% for the oral microbiome; 3.1 +/- 1.9% for the nasal microbiome; and 3.0
+/- 1.5% for the skin microbiome. CONCLUSIONS: The microbial environment of
academic animal care facilities varies significantly by location rather than
facility. Endotoxin is not a proxy for assessment of environmental microbial
exposures using 16S qPCR or 16S rDNA sequencing. The work microbiome contributes
to the composition of the nasal and skin microbiome of workers; the clinical
implications of this observation should be further studied.
PMID- 28704438
TI - Disentangling the root- and detritus-based food chain in the micro-food web of an
arable soil by plant removal.
AB - Soil food web structure and function is primarily determined by the major basal
resources, which are living plant tissue, root exudates and dead organic matter.
A field experiment was performed to disentangle the interlinkage of the root-and
detritus-based soil food chains. An arable site was cropped either with maize,
amended with maize shoot litter or remained bare soil, representing food webs
depending on roots, aboveground litter and soil organic matter as predominant
resource, respectively. The soil micro-food web, i.e. microorganisms and
nematodes, was investigated in two successive years along a depth transect. The
community composition of nematodes was used as model to determine the changes in
the rhizosphere, detritusphere and bulk soil food web. In the first growing
season the impact of treatments on the soil micro-food web was minor. In the
second year plant-feeding nematodes increased under maize, whereas after harvest
the Channel Index assigned promotion of the detritivore food chain, reflecting
decomposition of root residues. The amendment with litter did not foster
microorganisms, instead biomass of Gram-positive and Gram-negative bacteria as
well as that of fungi declined in the rooted zone. Likely higher grazing pressure
by nematodes reduced microbial standing crop as bacterial and fungal feeders
increased. However, populations at higher trophic levels were not promoted,
indicating limited flux of litter resources along the food chain. After two years
of bare soil microbial biomass and nematode density remained stable, pointing to
soil organic matter-based resources that allow bridging periods with deprivation.
Nematode communities were dominated by opportunistic taxa that are competitive at
moderate resource supply. In sum, removal of plants from the system had less
severe effects than expected, suggesting considerable food web resilience to the
disruption of both the root and detrital carbon channel, pointing to a legacy of
organic matter resources in arable soils.
PMID- 28704439
TI - Inner and inter population structure construction of Chinese Jiangsu Han
population based on Y23 STR system.
AB - In this study, we analyzed the genetic polymorphisms of 23 Y-STR loci from
PowerPlex(r) Y23 system in 916 unrelated healthy male individuals from Chinese
Jiangsu Han, and observed 912 different haplotypes including 908 unique
haplotypes and 4 duplicate haplotypes. The haplotype diversity reached 0.99999
and the discrimination capacity and match probability were 0.9956 and 0.0011,
respectively. The gene diversity values ranged from 0.3942 at DYS438 to 0.9607 at
DYS385a/b. Population differentiation within 10 Jiangsu Han subpopulations were
evaluated by RST values and visualized in Neighbor-Joining trees and Multi
Dimensional Scaling plots as well as population relationships between the Jiangsu
Han population and other 18 Eastern Asian populations. Such results indicated
that the 23 Y-STR loci were highly polymorphic in Jiangsu Han population and
played crucial roles in forensic application as well as population genetics. For
the first time, we reported the genetic diversity of male lineages in Jiangsu Han
population at a high-resolution level of 23 Y-STR set and consequently
contributed to familial searching, offender tracking, and anthropology analysis
of Jiangsu Han population.
PMID- 28704440
TI - Viral etiology, seasonality and severity of hospitalized patients with severe
acute respiratory infections in the Eastern Mediterranean Region, 2007-2014.
AB - INTRODUCTION: Little is known about the role of viral respiratory pathogens in
the etiology, seasonality or severity of severe acute respiratory infections
(SARI) in the Eastern Mediterranean Region. METHODS: Sentinel surveillance for
SARI was conducted from December 2007 through February 2014 at 20 hospitals in
Egypt, Jordan, Oman, Qatar and Yemen. Nasopharyngeal and oropharyngeal swabs were
collected from hospitalized patients meeting SARI case definitions and were
analyzed for infection with influenza, respiratory syncytial virus (RSV),
adenovirus (AdV), human metapneumovirus (hMPV) and human parainfluenza virus
types 1-3 (hPIV1-3). We analyzed surveillance data to calculate positivity rates
for viral respiratory pathogens, describe the seasonality of those pathogens and
determine which pathogens were responsible for more severe outcomes requiring
ventilation and/or intensive care and/or resulting in death. RESULTS: At least
one viral respiratory pathogen was detected in 8,753/28,508 (30.7%) samples
tested for at least one pathogen and 3,497/9,315 (37.5%) of samples tested for
all pathogens-influenza in 3,345/28,438 (11.8%), RSV in 3,942/24,503 (16.1%), AdV
in 923/9,402 (9.8%), hMPV in 617/9,384 (6.6%), hPIV1 in 159/9,402 (1.7%), hPIV2
in 85/9,402 (0.9%) and hPIV3 in 365/9,402 (3.9%). Multiple pathogens were
identified in 501/9,316 (5.4%) participants tested for all pathogens. Monthly
variation, indicating seasonal differences in levels of infection, was observed
for all pathogens. Participants with hMPV infections and participants less than
five years of age were significantly less likely than participants not infected
with hMPV and those older than five years of age, respectively, to experience a
severe outcome, while participants with a pre-existing chronic disease were at
increased risk of a severe outcome, compared to those with no reported pre
existing chronic disease. CONCLUSIONS: Viral respiratory pathogens are common
among SARI patients in the Eastern Mediterranean Region. Ongoing surveillance is
important to monitor changes in the etiology, seasonality and severity of
pathogens of interest.
PMID- 28704441
TI - A comparison of sex steroid concentration levels in the vitreous and serum of
patients with vitreoretinal diseases.
AB - The purpose of this study was to compare steroid hormone concentration levels in
the vitreous and serum of vitreoretinal disease patients to elucidate the
possibility of neurosteroid production in the retina. Serum and vitreous samples
were collected from vitrectomy patients, and estradiol (E2) and testosterone (T)
concentrations were measured using electro-chemiluminescence immunoassay. We
measured E2 in epiretinal membrane (ERM, n = 14), macular hole (MH, n = 18),
proliferative diabetic retinopathy (PDR, n = 20), and retinal detachment (RD, n =
19) cases, and T in ERM (n = 14), MH (n = 17), PDR (n = 13), and RD (n = 17)
cases. No statistically significant age differences existed among the groups.
Mean respective E2 concentrations (pg/ml) in the male/female vitreous were ERM:
6.67+/-4.04/18.82+/-7.10, MH: 10.3+/-7.02/17.00+/-4.8, PDR: 4.2+/-3.05/15.83+/
3.46, and RD: 10.00+/-4.58/16.06+/-4.57, while those in serum were ERM: 31.67+/
5.51/5.82+/-1.08, MH: 21.00+/-8.89/7.53+/-3.2, PDR: 29.20+/-7.07/12.75+/-10.62,
and RD: 24.33+/-6.51/7.5+/-4.42. E2 concentrations were significantly higher
(P<0.001) in the male serum than vitreous, yet significantly higher in the female
vitreous than serum. Mean respective T concentrations (ng/ml) in the male/female
vitreous were ERM: 0.15+/-0.03/0.15+/-0.01, MH: 0.15+/-0.01/0.15+/-0.01, PDR:
0.15+/-0.03/0.16+/-0.12, and RD: 0.14+/-0.01/0.17+/-0.08, while those in serum
were ERM: 4.54+/-1.46/0.16+/-0.01, MH: 8.04+/-2.29/0.16+/-0.10, PDR: 5.14+/
1.54/0.22+/-0.11, and RD: 3.24+/-0.75/0.17+/-0.10. T concentrations were high in
the male serum, yet extremely low in the male and female vitreous and female
serum. High concentrations of E2 were found in the vitreous, and women, in
particular, exhibited significantly higher concentrations in the vitreous than in
the serum. This finding suggests the possibility that in vitreoretinal disease
cases, the synthesis of E2 is increased locally only in female eyes.
PMID- 28704442
TI - Health professionals' perspective on the promotion of e-mental health apps in the
context of maternal depression.
AB - OBJECTIVE: Our study focuses on exploring (1) the intention of health
professionals to use and recommend e-mental health applications, (2) how this
intention of health professionals might be influenced, (3) which group of health
professionals might be most accessible to promote e-mental health applications
for maternal depression, and (4) for which tasks they rate them to be most
useful. MATERIALS AND METHODS: Based on a questionnaire informed by the theory of
planned behavior, we collected 131 responses of U.S., Spanish, and Swiss health
professionals in the field of pregnancy and maternal care (including
psychologists, psychiatrists, midwives, and doctors) by means of an online
survey. We analyzed the gathered data applying a structured equation model.
RESULTS: Our study reveals that health professionals would in general intend to
recommend and use e-mental health applications. However, their attitude towards e
mental health applications varies regarding the respective use cases and also
differs among health professions. CONCLUSION: We offer three alternative
propositions for private or public organizations, associations, or any other
entity whose purpose is service to the community for introducing e-mental health
applications into practice.
PMID- 28704443
TI - Dosimetric characteristics of a reusable 3D radiochromic dosimetry material.
AB - PURPOSE: To investigate the dosimetric characteristics of PRESAGEREU dosimeters.
METHODS: Commercially available PRESAGEREU dosimeters (size of 10 mm * 10 mm * 45
mm) were divided into two groups, with one of the groups placed at room
temperature of 22 degrees C (RT group) and another group placed at low
temperature of 10 degrees C (LT group). A total of 3 dosimeters (set of
dosimeters) were irradiated at a time, with doses of 1 Gy, 2 Gy, 4 Gy, 8 Gy, 12
Gy, 16 Gy, and 20 Gy, at a nominal dose rate of 400 MU/min at temperature of 22
degrees C. The dosimeters were irradiated three additional times by delivering
the same doses as those during the initial irradiations (4 irradiation cycles).
Optical density (OD) was assessed using optical CT scanning. RESULTS: Considering
both linearity and sensitivity of the OD curves, R2 above 0.95 and sensitivity
above 0.04 DeltaOD/Gy were observed at the 1st irradiation (reading time <= 6 h)
and 2nd irradiation (reading time = 0.5 h) for the RT group. For the LT group,
those values were observed at the 1st irradiation (reading time <= 2 h), and the
3rd and 4th irradiations (both reading times = 0.5 h). Considering the
reproducibility of signals in response to the same dose, dosimeters in the RT
group showed average deviations among dosimeters less than 5% (the 1st and 2nd
irradiations at the reading time of 0.5 h), while for dosimeters in the LT group
showed average deviations among dosimeters less than 6% (the 3rd and 4th
irradiations at the reading time of 0.5 h). For the rest, the OD curves were not
linear, sensitivities of the dosimeters were lower than 0.04 DeltaOD/Gy, and OD
deviations at the same dose were larger than 6%. CONCLUSIONS: At room
temperature, PRESAGEREU dosimeters could be used for dose measurement only for up
to two dose measurement sessions. At low temperatures, usage of PRESAGEREU
dosimeters for dose measurement seems to be possible from the 3rd irradiation.
When reusing PRESAGEREU dosimeters, the OD curve should be re-defined for every
measurement session because the shape of this curve depends on the irradiation
history.
PMID- 28704444
TI - Maternal inheritance of deltamethrin resistance in the salmon louse
Lepeophtheirus salmonis (Kroyer) is associated with unique mtDNA haplotypes.
AB - Parasitic infections by the salmon louse, Lepeophtheirus salmonis (Kroyer), cause
huge economic damage in salmon farming in the northern hemisphere, with combined
treatment costs and production losses in 2014 having been estimated at US$ 350
million for Norway (annual production 1.25 million tonnes). The control of L.
salmonis relies significantly on medicinal treatments, supplemented by non
pharmacological approaches. However, efficacy losses have been reported for
several delousing agents, including the pyrethroid deltamethrin. The aim of the
present study was to analyse the genetic basis of deltamethrin resistance in L.
salmonis. Deltamethrin median effective concentrations (EC50) were 0.28 MUg L-1
in the drug susceptible L. salmonis strain IoA-00 and 40.1 MUg L-1 in the
pyrethroid resistant strain IoA-02. IoA-00 and IoA-02 were crossed to produce
families spanning one parental and three filial generations (P0, F1-F3). In three
families derived from P0 crosses between an IoA-00 sire and an IoA-02 dam, 98.8%
of F2 parasites (n = 173) were resistant, i.e. remained unaffected after exposure
to 2.0 MUg L-1 deltamethrin. F3 parasites from these crosses showed a
deltamethrin EC50 of 9.66 MUg L-1. In two families of the inverse orientation at
P0 (IoA-02 sire x IoA-00 dam), 16.7% of F2 parasites were resistant (n = 84),
while the deltamethrin EC50 in F3 animals was 0.26 MUg L-1. The results revealed
a predominantly maternal inheritance of deltamethrin resistance. The 15,947-nt
mitochondrial genome was sequenced and compared among six unrelated L. salmonis
strains and parasites sampled from wild salmon in 2010. IoA-02 and three further
deltamethrin resistant strains, established from isolates originating from
different regions of Scotland, showed almost identical mitochondrial haplotypes.
In contrast, the mitochondrial genome was variable among susceptible strains and
L. salmonis from wild hosts. Deltamethrin caused toxicity and depletion of whole
body ATP levels in IoA-00 but not IoA-02 parasites. The maternal inheritance of
deltamethrin resistance and its association with mitochondrial haplotypes
suggests that pyrethroid toxicity in L. salmonis may involve molecular targets
encoded by mitochondrial genes.
PMID- 28704445
TI - Taxon abundance, diversity, co-occurrence and network analysis of the ruminal
microbiota in response to dietary changes in dairy cows.
AB - The ruminal microbiome, comprising large numbers of bacteria, ciliate protozoa,
archaea and fungi, responds to diet and dietary additives in a complex way. The
aim of this study was to investigate the benefits of increasing the depth of the
community analysis in describing and explaining responses to dietary changes.
Quantitative PCR, ssu rRNA amplicon based taxa composition, diversity and co
occurrence network analyses were applied to ruminal digesta samples obtained from
four multiparous Nordic Red dairy cows fitted with rumen cannulae. The cows
received diets with forage:concentrate ratio either 35:65 (diet H) or 65:35 (L),
supplemented or not with sunflower oil (SO) (0 or 50 g/kg diet dry matter),
supplied in a 4 * 4 Latin square design with a 2 * 2 factorial arrangement of
treatments and four 35-day periods. Digesta samples were collected on days 22 and
24 and combined. QPCR provided a broad picture in which a large fall in the
abundance of fungi was seen with SO in the H but not the L diet. Amplicon
sequencing showed higher community diversity indices in L as compared to H diets
and revealed diet specific taxa abundance changes, highlighting large differences
in protozoal and fungal composition. Methanobrevibacter ruminantium and Mbb.
gottschalkii dominated archaeal communities, and their abundance correlated
negatively with each other. Co-occurrence network analysis provided evidence that
no microbial domain played a more central role in network formation, that some
minor-abundance taxa were at nodes of highest centrality, and that microbial
interactions were diet specific. Networks added new dimensions to our
understanding of the diet effect on rumen microbial community interactions.
PMID- 28704446
TI - A specialist peer mentoring program for university students on the autism
spectrum: A pilot study.
AB - INTRODUCTION: The provision of peer mentoring may improve tertiary education
outcomes of students with autism spectrum disorder (ASD). This study evaluated
the pilot year of the Curtin Specialist Mentoring Program (CSMP), a specialised
peer mentoring program for university students with ASD aimed at improving self
reported well-being, academic success and retention in university studies.
METHODS: A single group pre-test, post-test design was employed. Quantitative and
qualitative evaluations were undertaken with 10 young adults with ASD to explore
the effectiveness and acceptability of the CSMP program. Students completed a
battery of questionnaires focused on general anxiety, state communication
apprehension, perceived communication competence, and communication apprehension
both prior to, and five months after commencing enrolment in the CSMP.
Information regarding academic success and retention was also obtained.
Interviews with participants provided further insight into their experience of
the program. RESULTS: Students enrolled in the CSMP showed significant
improvement in social support and general communication apprehension assessment
scores. Interviews revealed key features of the CSMP that may have contributed to
these positive outcomes. CONCLUSIONS: The current study provides preliminary
evidence that a specialised peer mentoring program can improve the well-being of
students with ASD, and highlights the importance of interventions which are
individualised, flexible, based on a social model, and target environmental
factors such as social support.
PMID- 28704447
TI - Sexual dimorphisms of mRNA and miRNA in human/murine heart disease.
AB - BACKGROUND: Sexual dimorphisms are well recognized in various cardiac diseases
such as ischemic cardiomyopathy (ICM), hypertrophic cardiomyopathy (HCM) and
dilated cardiomyopathy (DCM). Thorough understanding of the underlying genetic
programs is crucial to optimize treatment strategies specified for each gender.
By performing meta-analysis and microarray analysis, we sought to comprehensively
characterize the sexual dimorphisms in the healthy and diseased heart at the
level of both mRNA and miRNA transcriptome. RESULTS: Existing mRNA microarray
data of both mouse and human heart were integrated, identifying dozens/ hundreds
of sexually dimorphic genes in healthy heart, ICM, HCM, and DCM. These sexually
dimorphic genes overrepresented gene ontologies (GOs) important for cardiac
homeostasis. Further, microarray of miRNA, isolated from mouse sham left
ventricle (LV) (n = 6 & n = 5 for male & female) and chronic MI LV (n = 19 & n =
19) and from human normal LV (n = 6 & n = 6) and ICM LV (n = 4 & n = 5), was
conducted. This revealed that 13 mouse miRNAs are sexually dimorphic in MI and 6
in normal heart. In human, 3 miRNAs were sexually dimorphic in ICM and 15 in
normal heart. These data revealed miRNA-mRNA networks that operate in a sexually
biased fashion. CONCLUSIONS: mRNA and miRNA transcriptome of normal and disease
heart show significant sex differences, which might impact the cardiac
homeostasis. Together this study provides the first comprehensive picture of the
genome-wide program underlying the heart sexual dimorphisms, laying the
foundation for gender specific treatment strategies.
PMID- 28704448
TI - RNAi-based reverse genetics in the chelicerate model Tetranychus urticae: A
comparative analysis of five methods for gene silencing.
AB - RNA interference (RNAi) can be used for the protection against agricultural pests
through the silencing of genes required for pest fitness. To assess the potential
of RNAi approaches in the two-spotted spider mite, Tetranychus urticae, we
compared 5 methods for the delivery of double-stranded RNA (dsRNA). These methods
include mite feeding on either (i) leaves floating on a dsRNA solution, (ii)
dsRNA-expressing plants, (iii) artificial diet supplemented with dsRNA, or (iv)
dsRNA-coated leaves, and (v) mite soaking in a dsRNA solution. In all cases, the
gene targeted for method validation was the Vacuolar-type H+-ATPase (TuVATPase),
encoding a constitutively expressed ATP-driven proton pump located in the
membrane. Down-regulation of TuVATPase increased mortality and/or reduced
fecundity in all methods, but with variable efficiency. The most efficient
methods for dsRNA delivery were direct soaking of mites in the dsRNA solution and
mite feeding on dsRNA-coated leaves that mimics dsRNA application as a sprayable
pesticide. Both resulted in a dark-body phenotype not observed in mites treated
with a control dsRNA. Although with lower efficiency, dsRNA designed for
TuVATPase silencing and expressed in transgenic Arabidopsis plants impacted the
fitness of mites feeding on these plants. RNAi may thus be a valuable strategy to
control spider mite populations, either as a sprayable pesticide or through
transgenic crops. This comparative methodological study focusing on the induction
of RNAi-based gene silencing in T. urticae paves the way for reverse genetics
approaches in this model chelicerate system and prepares large-scale systematic
RNAi screens as a first step towards the development of specific RNA-based
pesticides. Such alternative molecules may help control spider mites that cause
significant damages to crops and ornamental plant species, as well as other
chelicerates detrimental to agriculture and health.
PMID- 28704449
TI - Postfire responses of the woody flora of Central Chile: Insights from a
germination experiment.
AB - Fire is a selective agent shaping plant traits and community assembly in fire
prone ecosystems. However, in ecosystems with no fire history, it can be a cause
of land degradation when it is suddenly introduced by humans, as plant species
may not be able to respond to such novel disturbance. Unlike other Mediterranean
type ecosystems (MTE) of the world, natural fires have not been frequent during
the Quaternary in the matorral of Central Chile, and thus, plant adaptive
responses are expected to be uncommon. We evaluated the effect of heat shock on
seed survival and germination of 21 native woody plants of the Chilean matorral
and compiled information on smoke-stimulation and resprouting, to evaluate the
importance of fire-adaptive responses in the context of the other MTE. We found
that in the Chilean woody flora negative seed responses to fire cues were more
frequent than positive responses. Although resprouting is a relatively widespread
trait, fire-stimulated germination is not as common in the Chilean matorral as in
other MTE. The seeds of seven endemic species were strongly damaged by fire cues
and this should be considered in post-fire restoration planning. However, our
results also showed that many species were resistant to elevated doses of heat
shock and in some, germination was even stimulated. Thus, future research should
focus on the evolutionary causes of these responses. These findings could help to
develop strategies for fire management in the Chilean matorral. In addition, they
will improve our understanding of the evolutionary forces that shaped this plant
community and to better frame this region among the other MTE worldwide.
PMID- 28704450
TI - A consensus layer V pyramidal neuron can sustain interpulse-interval coding.
AB - In terms of a single neuron's long-distance communication, interpulse intervals
(IPIs) are an attractive alternative to rate and binary codes. As a proxy for an
IPI, a neuron's time-to-spike can be found in the biophysical and experimental
intracellular literature. Using the current, consensus layer V pyramidal neuron,
the present study examines the feasibility of IPI-coding and examines the noise
sources that limit the information rate of such an encoding. In descending order
of importance, the noise sources are (i) synaptic variability, (ii) sodium
channel shot-noise, followed by (iii) thermal noise. The biophysical simulations
allow the calculation of mutual information, which is about 3.0 bits/spike. More
importantly, while, by any conventional definition, the biophysical model is
highly nonlinear, the underlying function that relates input intensity to the
defined output variable is linear. When one assumes the perspective of a neuron
coding via first hitting-time, this result justifies a pervasive and simplifying
assumption of computational modelers-that a class of cortical neurons can be
treated as linearly additive, computational devices.
PMID- 28704451
TI - Targeting of X-linked inhibitor of apoptosis protein and PI3-kinase/AKT signaling
by embelin suppresses growth of leukemic cells.
AB - The X-linked inhibitor of apoptosis (XIAP) is a viable molecular target for
anticancer drugs that overcome apoptosis-resistance of malignant cells. XIAP is
an inhibitor of apoptosis, mediating through its association with BIR3 domain of
caspase 9. Embelin, a quinone derivative isolated from the Embelia ribes plant,
has been shown to exhibit chemopreventive, anti-inflammatory, and apoptotic
activities via inhibiting XIAP activity. In this study, we found that embelin
causes a dose-dependent suppression of proliferation in leukemic cell lines K562
and U937. Embelin mediated inhibition of proliferation correlates with induction
of apoptosis. Furthermore, embelin treatment causes loss of mitochondrial
membrane potential and release of cytochrome c, resulting in subsequent
activation of caspase-3 followed by polyadenosin-5'-diphosphate-ribose polymerase
(PARP) cleavage. In addition, embelin treatment of leukemic cells results in a
decrease of constitutive phosphorylations/activation level of AKT and
downregulation of XIAP. Gene silencing of XIAP and AKT expression showed a link
between XIAP expression and activated AKT in leukemic cells. Interestingly,
targeting of XIAP and PI3-kinase/AKT signaling augmented inhibition of
proliferation and induction of apoptosis in leukemic cells. Altogether these
findings raise the possibility that embelin alone or in combination with
inhibitors of PI3-kinase/AKT pathway may have therapeutic usage in leukemia and
possibly other malignancies with up-regulated XIAP pathway.
PMID- 28704453
TI - Historical delta15N records of Saccharina specimens from oligotrophic waters of
Japan Sea (Hokkaido).
AB - Historically Saccharina spp. beds occurred along the west coast of Hokkaido, an
oligotrophic area, and were commercially exploited. Currently extensive
commercial Saccharina spp. beds do not form due to nutrient limitations. Here, we
postulate that nutrients assimilated by paleo-Saccharina spp. beds may have been
derived from spawning herrings (Clupea pallasii) acting as organisms that formed
a vector from their feeding grounds (Okhotsk Sea and Pacific Ocean) to their
spawning area (west coast of Hokkaido, Japan Sea). To test this hypothesis we
examined stable nitrogen isotope ratios (delta15N) of 100- to 135-year-old
Saccharina specimens preserved at the Herbarium (Hokkaido University Museum).
delta15N values of the paleo-Saccharina specimens collected from this region were
in the range of 100/00, which is significantly higher than the current 3-70/00 in
freshly sampled Saccharina spp. This high delta15N indicates that spawning
herring (Clupea pallasii) had potentially been a significant source of dissolved
inorganic nitrogen (DIN) absorbed by Saccharina, acting as an organism forming a
vector for transporting nutrients from eutrophic to oligotrophic coastal
ecosystems. Our findings support the hypothesis of so-called "herring-derived
nutrients."
PMID- 28704452
TI - Influence of lung CT changes in chronic obstructive pulmonary disease (COPD) on
the human lung microbiome.
AB - BACKGROUND: Changes in microbial community composition in the lung of patients
suffering from moderate to severe COPD have been well documented. However,
knowledge about specific microbiome structures in the human lung associated with
CT defined abnormalities is limited. METHODS: Bacterial community composition
derived from brush samples from lungs of 16 patients suffering from different CT
defined subtypes of COPD and 9 healthy subjects was analyzed using a cultivation
independent barcoding approach applying 454-pyrosequencing of 16S rRNA gene
fragment amplicons. RESULTS: We could show that bacterial community composition
in patients with changes in CT (either airway or emphysema type changes,
designated as severe subtypes) was different from community composition in lungs
of patients without visible changes in CT as well as from healthy subjects
(designated as mild COPD subtype and control group) (PC1, Padj = 0.002). Higher
abundance of Prevotella in samples from patients with mild COPD subtype and from
controls and of Streptococcus in the severe subtype cases mainly contributed to
the separation of bacterial communities of subjects. No significant effects of
treatment with inhaled glucocorticoids on bacterial community composition were
detected within COPD cases with and without abnormalities in CT in PCoA. Co
occurrence analysis suggests the presence of networks of co-occurring bacteria.
Four communities of positively correlated bacteria were revealed. The microbial
communities can clearly be distinguished by their associations with the CT
defined disease phenotype. CONCLUSION: Our findings indicate that CT detectable
structural changes in the lung of COPD patients, which we termed severe subtypes,
are associated with alterations in bacterial communities, which may induce
further changes in the interaction between microbes and host cells. This might
result in a changed interplay with the host immune system.
PMID- 28704454
TI - Indocyanine green kinetics with near-infrared spectroscopy predicts cerebral
hyperperfusion syndrome after carotid artery stenting.
AB - BACKGROUND: Cerebral hyperperfusion syndrome (HPS) is a potentially life
threatening complication following carotid artery stenting (CAS) and carotid
endoarterectomy (CEA). Early prediction and treatment of patients at risk for HPS
are required in patients undergoing CAS because HPS occurs significantly earlier
after CAS than CEA. Near-infrared spectroscopy (NIRS) is often used for
monitoring, and indocyanine green (ICG) kinetics by NIRS (ICG-NIRS) can detect
reductions in cerebral perfusion in patients with acute stroke. However, whether
ICG-NIRS can predict postoperative hyperperfusion phenomenon (HP) after carotid
revascularization is unclear. OBJECTIVE: Here, we evaluated whether the blood
flow index (BFI) ratio calculated from a time-intensity curve from ICG-NIRS
monitoring can predict HPS after CAS. METHODS: The BFI ratio was prospectively
monitored using ICG-NIRS in 135 patients undergoing CAS. Preoperative
cerebrovascular reactivity (CVR) and the postoperative asymmetry index (AI) were
also assessed with single-photon emission computed tomography before and after
CAS, and the correlation was evaluated. In addition, patients were divided into
two groups, a non-HP group (n = 113) and an HP group (n = 22), and we evaluated
the correlation with hemodynamic impairment in the ipsilateral hemisphere and
clinical results. RESULTS: Twenty-two cases (16%) showed HP, and four (3%) showed
HPS after CAS. The BFI ratio calculated from ICG-NIRS showed a significant linear
correlation with preoperative CVR and postoperative AI (r = -0.568, 0.538, P <
0.001, <0.001, respectively). The degree of stenosis, the rate of no cross flow,
preoperative CVR, and the incidence of HPS were significantly different between
the groups. CONCLUSIONS: Measurement of ICG kinetics by NIRS is useful for
detection of HPS in patients who underwent CAS.
PMID- 28704455
TI - A density-based approach for detecting complexes in weighted PPI networks by
semantic similarity.
AB - Protein complex detection in PPI networks plays an important role in analyzing
biological processes. A new algorithm-DBGPWN-is proposed for predicting complexes
in PPI networks. Firstly, a method based on gene ontology is used to measure
semantic similarities between interacted proteins, and the similarity values are
used as their weights. Then, a density-based graph partitioning algorithm is
developed to find clusters in the weighted PPI networks, and the identified ones
are considered to be dense and similar. Experimental results demonstrate that our
approach achieves good performance as compared with such algorithms as MCL, CMC,
MCODE, RNSC, CORE, ClusterOne and FGN.
PMID- 28704456
TI - Atg4 plays an important role in efficient expansion of autophagic isolation
membranes by cleaving lipidated Atg8 in Saccharomyces cerevisiae.
AB - Autophagy, an intracellular degradation system, is highly conserved among
eukaryotes from yeast to mammalian cells. In the yeast Saccharomyces cerevisiae,
most Atg (autophagy-related) proteins, which are essential for autophagosome
formation, are recruited to a restricted region close to the vacuole, termed the
vacuole-isolation membrane contact site (VICS), upon induction of autophagy.
Subsequently, the isolation membrane (IM) expands and sequesters cytoplasmic
materials to become a closed autophagosome. In S. cerevisiae, the ubiquitin-like
protein Atg8 is C-terminally conjugated to the phospholipid
phosphatidylethanolamine (PE) to generate Atg8-PE. During autophagosome
formation, Atg8-PE is cleaved by Atg4 to release delipidated Atg8 (Atg8G116) and
PE. Although delipidation of Atg8-PE is important for autophagosome formation, it
remains controversial whether the delipidation reaction is required for targeting
of Atg8 to the VICS or for subsequent IM expansion. We used an IM visualization
technique to clearly demonstrate that delipidation of Atg8-PE is dispensable for
targeting of Atg8 to the VICS, but required for IM expansion. Moreover, by
overexpressing Atg8G116, we showed that the delipidation reaction of Atg8-PE by
Atg4 plays an important role in efficient expansion of the IM other than
supplying unlipidated Atg8G116. Finally, we suggested the existence of biological
membranes at the Atg8-labeled structures in Atg8-PE delipidation-defective cells,
but not at those in atg2Delta cells. Taken together, it is likely that Atg2 is
involved in localization of biological membranes to the VICS, where Atg4 is
responsible for IM expansion.
PMID- 28704457
TI - The theory, direction, and magnitude of ecosystem fire probability as constrained
by precipitation and temperature.
AB - The effects of climate on wildland fire confronts society across a range of
different ecosystems. Water and temperature affect the combustion dynamics,
irrespective of whether those are associated with carbon fueled motors or
ecosystems, but through different chemical, physical, and biological processes.
We use an ecosystem combustion equation developed with the physical chemistry of
atmospheric variables to estimate and simulate fire probability and mean fire
interval (MFI). The calibration of ecosystem fire probability with basic
combustion chemistry and physics offers a quantitative method to address wildland
fire in addition to the well-studied forcing factors such as topography,
ignition, and vegetation. We develop a graphic analysis tool for estimating
climate forced fire probability with temperature and precipitation based on an
empirical assessment of combustion theory and fire prediction in ecosystems.
Climate-affected fire probability for any period, past or future, is estimated
with given temperature and precipitation. A graphic analyses of wildland fire
dynamics driven by climate supports a dialectic in hydrologic processes that
affect ecosystem combustion: 1) the water needed by plants to produce carbon
bonds (fuel) and 2) the inhibition of successful reactant collisions by water
molecules (humidity and fuel moisture). These two postulates enable a
classification scheme for ecosystems into three or more climate categories using
their position relative to change points defined by precipitation in combustion
dynamics equations. Three classifications of combustion dynamics in ecosystems
fire probability include: 1) precipitation insensitive, 2) precipitation
unstable, and 3) precipitation sensitive. All three classifications interact in
different ways with variable levels of temperature.
PMID- 28704458
TI - "The care is the best you can give at the time": Health care professionals'
experiences in providing gender affirming care in South Africa.
AB - BACKGROUND: While the provision of gender affirming care for transgender people
in South Africa is considered legal, ethical, and medically sound, and is
theoretically-available in both the South African private and public health
sectors, access remains severely limited and unequal within the country. As there
are no national policies or guidelines, little is known about how individual
health care professionals providing gender affirming care make clinical decisions
about eligibility and treatment options. METHOD: Based on an initial policy
review and service mapping, this study employed semi-structured interviews with a
snowball sample of twelve health care providers, representing most providers
currently providing gender affirming care in South Africa. Data were analysed
thematically using NVivo, and are reported following COREQ guidelines. RESULTS:
Our findings suggest that, whilst a small minority of health care providers offer
gender affirming care, this is almost exclusively on their own initiative and is
usually unsupported by wider structures and institutions. The ad hoc,
discretionary nature of services means that access to care is dependent on
whether a transgender person is fortunate enough to access a sympathetic and
knowledgeable health care provider. CONCLUSION: Accordingly, national, state
sanctioned guidelines for gender affirming care are necessary to increase access,
homogenise quality of care, and contribute to equitable provision of gender
affirming care in the public and private health systems.
PMID- 28704459
TI - Prevalence of drug-resistant tuberculosis in Nigeria: A systematic review and
meta-analysis.
AB - BACKGROUND: Drug-resistant tuberculosis (TB) undermines control efforts and its
burden is poorly understood in resource-limited settings. We performed a
systematic review and meta-analysis to provide an up-to-date summary of the
extent of drug-resistant TB in Nigeria. METHODS: We searched PubMed, Scopus,
Embase, HINARI, AJOL, the Cochrane library, Web of Science, and Google Scholar
for reports published before January 31 2017, that included any resistance, mono
resistance or multidrug resistance to anti-TB drugs in Nigeria. Summary estimates
were calculated using random effects models. RESULTS: We identified 34 anti-TB
drug resistance surveys with 8002 adult TB patients consisting of 2982 new and
5020 previously-treated cases. The prevalence rate of any drug resistance among
new TB cases was 32.0% (95% CI 24.0-40.0%; 734/2892) and among previously-treated
cases, the rate was 53.0% (95% CI 35.0-71.0%; 1467/5020). Furthermore, multidrug
resistance among new and previously-treated cases was 6.0% (95% CI 4.0
8.0%;161/2502)and 32.0% (95%CI 20.0-44.0; 357/949), respectively. There was
significant heterogeneity between the studies (p<0.001, I2 tests). The prevalence
of drug-resistant TB varied according to methods of drug susceptibility testing
and geographic region of Nigeria. CONCLUSION: The burden of drug-resistant TB in
Nigeria is high. We recommend that a national anti-TB drug resistance survey be
carried out, and strategies for case detection and programmatic management of
drug-resistant TB in Nigeria need to be strengthened.
PMID- 28704460
TI - Effects of reactive social distancing on the 1918 influenza pandemic.
AB - The 1918 influenza pandemic was characterized by multiple epidemic waves. We
investigated reactive social distancing, a form of behavioral response where
individuals avoid potentially infectious contacts in response to available
information on an ongoing epidemic or pandemic. We modelled its effects on the
three influenza waves in the United Kingdom. In previous studies, human
behavioral response was modelled by a Power function of the proportion of recent
influenza mortality in a population, and by a Hill function, which is a function
of the number of recent influenza mortality. Using a simple epidemic model with a
Power function and one common set of parameters, we provided a good model fit for
the observed multiple epidemic waves in London boroughs, Birmingham and
Liverpool. We further applied the model parameters from these three cities to all
334 administrative units in England and Wales and including the population sizes
of individual administrative units. We computed the Pearson's correlation between
the observed and simulated for each administrative unit. We found a median
correlation of 0.636, indicating that our model predictions are performing
reasonably well. Our modelling approach is an improvement from previous studies
where separate models are fitted to each city. With the reduced number of model
parameters used, we achieved computational efficiency gain without over-fitting
the model. We also showed the importance of reactive behavioral distancing as a
potential non-pharmaceutical intervention during an influenza pandemic. Our work
has both scientific and public health significance.
PMID- 28704461
TI - Assessing the performance of remotely-sensed flooding indicators and their
potential contribution to early warning for leptospirosis in Cambodia.
AB - Remote sensing can contribute to early warning for diseases with environmental
drivers, such as flooding for leptospirosis. In this study we assessed whether
and which remotely-sensed flooding indicator could be used in Cambodia to study
any disease for which flooding has already been identified as an important
driver, using leptospirosis as a case study. The performance of six potential
flooding indicators was assessed by ground truthing. The Modified Normalized
Difference Water Index (MNDWI) was used to estimate the Risk Ratio (RR) of being
infected by leptospirosis when exposed to floods it detected, in particular
during the rainy season. Chi-square tests were also calculated. Another variable
the time elapsed since the first flooding of the year-was created using MNDWI
values and was also included as explanatory variable in a generalized linear
model (GLM) and in a boosted regression tree model (BRT) of leptospirosis
infections, along with other explanatory variables. Interestingly, MNDWI
thresholds for both detecting water and predicting the risk of leptospirosis
seroconversion were independently evaluated at -0.3. Value of MNDWI greater than
0.3 was significantly related to leptospirosis infection (RR = 1.61 [1.10-1.52];
chi2 = 5.64, p-value = 0.02, especially during the rainy season (RR = 2.03 [1.25
3.28]; chi2 = 8.15, p-value = 0.004). Time since the first flooding of the year
was a significant risk factor in our GLM model (p-value = 0.042). These results
suggest that MNDWI may be useful as a risk indicator in an early warning remote
sensing tool for flood-driven diseases like leptospirosis in South East Asia.
PMID- 28704462
TI - A longitudinal MRI study on lymph nodes histiocytosis of a xenograft cancer
model.
AB - BACKGROUND: Efforts are continuously made to detect and investigate the pivotal
processes and interplay between the response of sentinel lymph node and malignant
cells from a primary tumor. Conversely, some frequently used tumor animal models,
such as human cancer xenografts, rarely feature metastasis. Therefore, lymph node
alterations are seldom assessed. We consider that studying lymph node response
could contribute to the understanding of host reaction to cancer. In the present
study, we explored the presence of regional lymph node alterations in parallel
with tumor growth using a pancreatic tumor xenograft model which does not develop
metastasis. METHODS AND FINDINGS: We established an animal cancer model by the
subcutaneous inoculation of PANC-1 (a metastatic human pancreatic cancer cell
line) in the left upper flank of athymic nude mice. Tumor animals, along with
controls (n = 7 / group) were subjected to Magnetic Resonance Imaging (MRI) in
order to follow tumor growth and brachial and axillary lymph nodes alterations
over several weeks. Further histological analyses were performed at the end of
the study. The individual average of the different lymph nodes sizes was 15-40%
larger in the tumor animals compared to control animals at week 8 to week 20. The
tumor size and lymph node size were not correlated. Histological analysis of the
lymph nodes showed paracortical histiocytosis. No metastasis to lymph nodes could
be detected by histology. In tumor bearing animals, histiocytosis was associated
with isolated apoptotic bodies and migration of human tumoral cells was confirmed
by specific immunostaining of human origin markers. CONCLUSIONS: The lack of
metastasis as well as the pathological manifestation of the lymph node alteration
in this pre-clinical model established here parallels findings in patients with
sinus histiocytosis that is correlated with improved survival.
PMID- 28704463
TI - A novel non-invasive diagnostic sampling technique for cutaneous leishmaniasis.
AB - Accurate diagnosis of cutaneous leishmaniasis (CL) is important for chemotherapy
and epidemiological studies. Common approaches for Leishmania detection involve
the invasive collection of specimens for direct identification of amastigotes by
microscopy and the culturing of promastigotes from infected tissues. Although
these techniques are highly specific, they require highly skilled health workers
and have the inherent risks of all invasive procedures, such as pain and risk of
bacterial and fungal super-infection. Therefore, it is essential to reduce
discomfort, potential infection and scarring caused by invasive diagnostic
approaches especially for children. In this report, we present a novel non
invasive method, that is painless, rapid and user-friendly, using sequential tape
strips for sampling and isolation of DNA from the surface of active and healed
skin lesions of CL patients. A total of 119 patients suspected of suffering from
cutaneous leishmaniasis with different clinical manifestations were recruited and
samples were collected both from their lesions and from uninfected areas. In
addition, 15 fungal-infected lesions and 54 areas of healthy skin were examined.
The duration of sampling is short (less than one minute) and species
identification by PCR is highly specific and sensitive. The sequential tape
stripping sampling method is a sensitive, non-invasive and cost-effective
alternative to traditional diagnostic assays and it is suitable for field studies
as well as for use in health care centers.
PMID- 28704464
TI - Simulated impacts of ankle foot orthoses on muscle demand and recruitment in
typically-developing children and children with cerebral palsy and crouch gait.
AB - Passive ankle foot orthoses (AFOs) are often prescribed for children with
cerebral palsy (CP) to assist locomotion, but predicting how specific device
designs will impact energetic demand during gait remains challenging. Powered
AFOs have been shown to reduce energy costs of walking in unimpaired adults more
than passive AFOs, but have not been tested in children with CP. The goal of this
study was to investigate the potential impact of powered and passive AFOs on
muscle demand and recruitment in children with CP and crouch gait. We simulated
gait for nine children with crouch gait and three typically-developing children
with powered and passive AFOs. For each AFO design, we computed reductions in
muscle demand compared to unassisted gait. Powered AFOs reduced muscle demand 15
44% compared to unassisted walking, 1-14% more than passive AFOs. A slower
walking speed was associated with smaller reductions in absolute muscle demand
for all AFOs (r2 = 0.60-0.70). However, reductions in muscle demand were only
moderately correlated with crouch severity (r2 = 0.40-0.43). The ankle
plantarflexor muscles were most heavily impacted by the AFOs, with gastrocnemius
recruitment decreasing 13-73% and correlating with increasing knee flexor moments
(r2 = 0.29-0.91). These findings support the potential use of powered AFOs for
children with crouch gait, and highlight how subject-specific kinematics and
kinetics may influence muscle demand and recruitment to inform AFO design.
PMID- 28704465
TI - Lipoprotein(a) in patients with aortic stenosis: Insights from cardiovascular
magnetic resonance.
AB - BACKGROUND: Aortic stenosis is the most common age-related valvular pathology.
Patients with aortic stenosis and myocardial fibrosis have worse outcome but the
underlying mechanism is unclear. Lipoprotein(a) is associated with adverse
cardiovascular risk and is elevated in patients with aortic stenosis. Although
mechanistic pathways could link Lipoprotein(a) with myocardial fibrosis, whether
the two are related has not been previously explored. In this study, we
investigated whether elevated Lipoprotein(a) was associated with the presence of
myocardial replacement fibrosis. METHODS: A total of 110 patients with mild,
moderate and severe aortic stenosis were assessed by late gadolinium enhancement
(LGE) cardiovascular magnetic resonance to identify fibrosis. Mann Whitney U
tests were used to assess for evidence of an association between Lp(a) and the
presence or absence of myocardial fibrosis and aortic stenosis severity and
compared to controls. Univariable and multivariable linear regression analysis
were undertaken to identify possible predictors of Lp(a). RESULTS: Thirty-six
patients (32.7%) had no LGE enhancement, 38 (34.6%) had midwall enhancement
suggestive of midwall fibrosis and 36 (32.7%) patients had subendocardial
myocardial fibrosis, typical of infarction. The aortic stenosis patients had
higher Lp(a) values than controls, however, there was no significant difference
between the Lp(a) level in mild, moderate or severe aortic stenosis. No
association was observed between midwall or infarction pattern fibrosis and
Lipoprotein(a), in the mild/moderate stenosis (p = 0.91) or severe stenosis
patients (p = 0.42). CONCLUSION: There is no evidence to suggest that higher
Lipoprotein(a) leads to increased myocardial midwall or infarction pattern
fibrosis in patients with aortic stenosis.
PMID- 28704466
TI - Hand-arm vibration and the risk of vascular and neurological diseases-A
systematic review and meta-analysis.
AB - BACKGROUND: Increased occurrence of Raynaud's phenomenon, neurosensory injury and
carpal tunnel syndrome has been reported for more than 100 years in association
with work with vibrating machines. The current risk prediction modelling (ISO
5349) for "Raynaud's phenomenon" is based on a few studies published 70 to 40
years ago. There are no corresponding risk prediction models for neurosensory
injury or carpal tunnel syndrome, nor any systematic reviews comprising a
statistical synthesis (meta-analysis) of the evidence. OBJECTIVES: Our aim was to
provide a systematic review of the literature on the association between
Raynaud's phenomenon, neurosensory injuries and carpal tunnel syndrome and hand
arm vibration (HAV) exposure. Moreover the aim was to estimate the magnitude of
such an association using meta-analysis. METHODS: This systematic review covers
the scientific literature up to January 2016. The databases used for the
literature search were PubMed and Science Direct. We found a total of 4,335
abstracts, which were read and whose validity was assessed according to pre
established criteria. 294 articles were examined in their entirety to determine
whether each article met the inclusion criteria. The possible risk of bias was
assessed for each article. 52 articles finally met the pre-established criteria
for inclusion in the systematic review. RESULTS: The results show that workers
who are exposed to HAV have an increased risk of vascular and neurological
diseases compared to non-vibration exposed groups. The crude estimate of the risk
increase is approximately 4-5 fold. The estimated effect size (odds ratio) is 6.9
for the studies of Raynaud's phenomenon when including only the studies judged to
have a low risk of bias. The corresponding risk of neurosensory injury is 7.4 and
the equivalent of carpal tunnel syndrome is 2.9. CONCLUSION: At equal exposures,
neurosensory injury occurs with a 3-time factor shorter latency than Raynaud's
phenomenon. Which is why preventive measures should address this vibration health
hazard with greater attention.
PMID- 28704467
TI - Locomotor adaptability in persons with unilateral transtibial amputation.
AB - BACKGROUND: Locomotor adaptation enables walkers to modify strategies when faced
with challenging walking conditions. While a variety of neurological injuries can
impair locomotor adaptability, the effect of a lower extremity amputation on
adaptability is poorly understood. OBJECTIVE: Determine if locomotor adaptability
is impaired in persons with unilateral transtibial amputation (TTA). METHODS: The
locomotor adaptability of 10 persons with a TTA and 8 persons without an
amputation was tested while walking on a split-belt treadmill with the parallel
belts running at the same (tied) or different (split) speeds. In the split
condition, participants walked for 15 minutes with the respective belts moving at
0.5 m/s and 1.5 m/s. Temporal spatial symmetry measures were used to evaluate
reactive accommodations to the perturbation, and the adaptive/de-adaptive
response. RESULTS: Persons with TTA and the reference group of persons without
amputation both demonstrated highly symmetric walking at baseline. During the
split adaptation and tied post-adaptation walking both groups responded with the
expected reactive accommodations. Likewise, adaptive and de-adaptive responses
were observed. The magnitude and rate of change in the adaptive and de-adaptive
responses were similar for persons with TTA and those without an amputation.
Furthermore, adaptability was no different based on belt assignment for the
prosthetic limb during split adaptation walking. CONCLUSIONS: Reactive changes
and locomotor adaptation in response to a challenging and novel walking condition
were similar in persons with TTA to those without an amputation. Results suggest
persons with TTA have the capacity to modify locomotor strategies to meet the
demands of most walking conditions despite challenges imposed by an amputation
and use of a prosthetic limb.
PMID- 28704468
TI - ThMYC4E, candidate Blue aleurone 1 gene controlling the associated trait in
Triticum aestivum.
AB - Blue aleurone is a useful and interesting trait in common wheat that was derived
from related species. Here, transcriptomes of blue and white aleurone were
compared for isolating Blue aleurone 1 (Ba1) transferred from Thinopyrum
ponticum. In the genes involved in anthocyanin biosynthesis, only a basic helix
loop-helix (bHLH) transcription factor, ThMYC4E, had a higher transcript level in
blue aleurone phenotype, and was homologous to the genes on chromosome 4 of
Triticum aestivum. ThMYC4E carried the characteristic domains (bHLH-MYC_N, HLH
and ACT-like) of a bHLH transcription factor, and clustered with genes regulating
anthocyanin biosynthesis upon phylogenetic analysis. The over-expression of
ThMYC4E regulated anthocyanin biosynthesis with the coexpression of the MYB
transcription factor ZmC1 from maize. ThMYC4E existed in the genomes of the
addition, substitution and near isogenic lines with the blue aleurone trait
derived from Th. ponticum, and could not be detected in any germplasm of T.
urartu, T. monococcum, T. turgidum, Aegilops tauschii or T. aestivum, with white
aleurone. These results suggested that ThMYC4E was candidate Ba1 gene controlling
the blue aleurone trait in T. aestivum genotypes carrying Th. ponticum
introgression. The ThMYC4E isolation aids in better understanding the genetic
mechanisms of the blue aleurone trait and in its more effective use during wheat
breeding.
PMID- 28704469
TI - The relationship between a low grain intake dietary pattern and impulsive
behaviors in middle-aged Japanese people.
AB - Several studies indicate that dietary habits are associated with mental health.
We are interested in identifying not a specific single nutrient/food group but
the population preferring specific food combinations that can be related to
mental health. Very few studies have examined relationships between dietary
patterns and multifaceted mental states using cluster analysis. The purpose of
this study was to investigate population-level dietary patterns associated with
mental state using cluster analysis. We focused on depressive state, sleep
quality, subjective well-being, and impulsive behaviors using rating scales. Two
hundred and seventy-nine Japanese middle-aged people participated in the present
study. Dietary pattern was estimated using a brief self-administered diet-history
questionnaire (the BDHQ). We conducted K-means cluster analysis using thirteen
BDHQ food groups: milk, meat, fish, egg, pulses, potatoes, green and yellow
vegetables, other vegetables, mushrooms, seaweed, sweets, fruits, and grain. We
identified three clusters characterized as "vegetable and fruit dominant," "grain
dominant," and "low grain tendency" subgroups. The vegetable and fruit dominant
group showed increases in several aspects of subjective well-being demonstrated
by the SF-8. Differences in mean subject characteristics across clusters were
tested using ANOVA. The low frequency intake of grain group showed higher
impulsive behavior, demonstrated by BIS-11 deliberation and sum scores. The
present study demonstrated that traditional Japanese dietary patterns, such as
eating rice, can help with beneficial changes in mental health.
PMID- 28704470
TI - Mammary candidiasis: A medical condition without scientific evidence?
AB - Many physicians, midwives and lactation consultants still believe that yeasts
(particularly Candida spp.) play an important role as an agent of nipple and
breast pain despite the absolute absence of scientific proofs to establish such
association. In this context, the objective of this study was to investigate the
microorganisms involved in sore nipples and/or painful "shooting" breastfeeding
by using a variety of microscopy techniques, as well as culture-dependent and
independent identification methods. Initially, 60 women (30 diagnosed as
suffering "mammary candidiasis" and 30 with no painful breastfeeding) were
recruited to elucidate the role of their pumps on the milk microbial profiles.
After realizing the bias introduced by using such devices, manual expression was
selected as the collection method for the microbiological analysis of milk
samples provided by 529 women with symptoms compatible with "mammary
candidiasis". Nipple swabs and nipple biopsy samples were also collected from the
participating women. Results showed that the role played by yeasts in breast and
nipple pain is, if any, marginal. In contrast, our results strongly support that
coagulase-negative staphylococci and streptococci (mainly from the mitis and
salivarius groups) are the agents responsible for such cases. As a consequence,
and following the recommendations of the US Library of Medicine for the
nomenclature of infectious diseases, the term "mammary candidiasis" or "nipple
thrush" should be avoided when referring to such condition and replaced by
"subacute mastitis".
PMID- 28704471
TI - Linear systems with unstructured multiplicative uncertainty: Modeling and robust
stability analysis.
AB - This article deals with continuous-time Linear Time-Invariant (LTI) Single-Input
Single-Output (SISO) systems affected by unstructured multiplicative uncertainty.
More specifically, its aim is to present an approach to the construction of
uncertain models based on the appropriate selection of a nominal system and a
weight function and to apply the fundamentals of robust stability investigation
for considered sort of systems. The initial theoretical parts are followed by
three extensive illustrative examples in which the first order time-delay, second
order and third order plants with parametric uncertainty are modeled as systems
with unstructured multiplicative uncertainty and subsequently, the robust
stability of selected feedback loops containing constructed models and chosen
controllers is analyzed and obtained results are discussed.
PMID- 28704472
TI - Prevention of mother-to-child transmission of HIV Option B+ cascade in rural
Tanzania: The One Stop Clinic model.
AB - BACKGROUND: Strategies to improve the uptake of Prevention of Mother-To-Child
Transmission of HIV (PMTCT) are needed. We integrated HIV and maternal, newborn
and child health services in a One Stop Clinic to improve the PMTCT cascade in a
rural Tanzanian setting. METHODS: The One Stop Clinic of Ifakara offers integral
care to HIV-infected pregnant women and their families at one single place and
time. All pregnant women and HIV-exposed infants attended during the first year
of Option B+ implementation (04/2014-03/2015) were included. PMTCT was assessed
at the antenatal clinic (ANC), HIV care and labour ward, and compared with the
pre-B+ period. We also characterised HIV-infected pregnant women and evaluated
the MTCT rate. RESULTS: 1,579 women attended the ANC. Seven (0.4%) were known to
be HIV-infected. Of the remainder, 98.5% (1,548/1,572) were offered an HIV test,
94% (1,456/1,548) accepted and 38 (2.6%) tested HIV-positive. 51 were re-screened
for HIV during late pregnancy and one had seroconverted. The HIV prevalence at
the ANC was 3.1% (46/1,463). Of the 39 newly diagnosed women, 35 (90%) were
linked to care. HIV test was offered to >98% of ANC clients during both the pre-
and post-B+ periods. During the post-B+ period, test acceptance (94% versus
90.5%, p<0.0001) and linkage to care (90% versus 26%, p<0.0001) increased. Ten
additional women diagnosed outside the ANC were linked to care. 82% (37/45) of
these newly-enrolled women started antiretroviral treatment (ART). After a median
time of 17 months, 27% (12/45) were lost to follow-up. 79 women under HIV care
became pregnant and all received ART. After a median follow-up time of 19 months,
6% (5/79) had been lost. 5,727 women delivered at the hospital, 20% (1,155/5,727)
had unknown HIV serostatus. Of these, 30% (345/1,155) were tested for HIV, and
18/345 (5.2%) were HIV-positive. Compared to the pre-B+ period more women were
tested during labour (30% versus 2.4%, p<0.0001). During the study, the MTCT rate
was 2.2%. CONCLUSIONS: The implementation of Option B+ through an integrated
service delivery model resulted in universal HIV testing in the ANC, high rates
of linkage to care, and MTCT below the elimination threshold. However, HIV
testing in late pregnancy and labour, and retention during early ART need to be
improved.
PMID- 28704473
TI - Enriched environment and stress exposure influence splenic B lymphocyte
composition.
AB - Prolonged chronic stress has deleterious effects on immune function and is
associated with numerous negative health outcomes. The spleen harbors one-fourth
of the body's lymphocytes and mediates both innate and adaptive immune responses.
However, the subset of splenic lymphocytes that respond, either adaptively or
maladaptively, to various stressors remains largely unknown. Here we investigated
the effects of unpredictable chronic mild stress (CMS) exposure on spleen
composition in male mice housed in two different caging conditions: standard
caging (Cntl) and enriched environment (EE). EE-caged mice exhibited the greatest
absolute number of splenocytes and CMS exposure significantly lowered splenocyte
numbers in both caging conditions. Glucocorticoid production, measured by mean
fecal corticosterone metabolites (FCM), was significantly lower in EE-caged mice
vs. Cntl-caged mice. Surprisingly, CMS exposure resulted in an increase in mean
FCM in EE-caged mice, but no significant change in Cntl-caged mice. CMS altered
the splenic B:T lymphocyte ratio; it reduced the frequency of B cells, but
increased the frequency of T cells in EE-caged mice. Splenocyte number and B:T
lymphocyte ratio showed a negative relationship with mean FCM. EE-caged mice had
a lower frequency of immature and germinal B cells than Cntl-caged mice. CMS
markedly increased the frequency of immature and marginal zone B cells, but
decreased the frequency of follicular B cells in both caging conditions. Mean FCM
correlated positively with frequency of immature, marginal zone and germinal
center B cells, but negatively with frequency of follicular B cells. To conclude,
splenic immune cells, particularly B lymphocyte composition, are modulated by
caging environment and stress and may prime mice differently to respond to immune
challenges.
PMID- 28704474
TI - Dietary hemoglobin rescues young piglets from severe iron deficiency anemia:
Duodenal expression profile of genes involved in heme iron absorption.
AB - Heme is an efficient source of iron in the diet, and heme preparations are used
to prevent and cure iron deficiency anemia in humans and animals. However, the
molecular mechanisms responsible for heme absorption remain only partially
characterized. Here, we employed young iron-deficient piglets as a convenient
animal model to determine the efficacy of oral heme iron supplementation and
investigate the pathways of heme iron absorption. The use of bovine hemoglobin as
a dietary source of heme iron was found to efficiently counteract the development
of iron deficiency anemia in piglets, although it did not fully rebalance their
iron status. Our results revealed a concerted increase in the expression of genes
responsible for apical and basolateral heme transport in the duodenum of piglets
fed a heme-enriched diet. In these animals the catalytic activity of heme
oxygenase 1 contributed to the release of elemental iron from the protoporphyrin
ring of heme within enterocytes, which may then be transported by the strongly
expressed ferroportin across the basolateral membrane to the circulation. We
hypothesize that the well-recognized high bioavailability of heme iron may depend
on a split pathway mediating the transport of heme-derived elemental iron and
intact heme from the interior of duodenal enterocytes to the bloodstream.
PMID- 28704475
TI - Protective effect of Galectin-9 in murine model of lung emphysema: Involvement of
neutrophil migration and MMP-9 production.
AB - PURPOSE: Chronic obstructive pulmonary disease (COPD) is characterized by
irreversible airflow obstruction and pulmonary emphysema. Persistent inflammation
and remodeling of the lungs and airways result in reduced lung function and a
lower quality of life. Galectin (Gal)-9 plays a crucial role as an immune
modulator in various diseases. However, its role in the pathogenesis of pulmonary
emphysema is unknown. This study investigates whether Gal-9 is involved in
pulmonary inflammation and changes in emphysema in a porcine pancreatic elastase
(PPE)-induced emphysema model. MATERIALS AND METHODS: Gal-9 was administered to
mice subcutaneously once daily from 1 day before PPE instillation to day 5.
During the development of emphysema, lung tissue and bronchoalveolar lavage fluid
(BALF) were collected. Histological and cytological findings, concentrations of
chemokines and matrix metalloproteinases (MMPs) in the BALF, and the influence of
Gal-9 treatment on neutrophils were analyzed. RESULTS: Gal-9 suppressed the
pathological changes of PPE-induced emphysema. The mean linear intercept (Lm) of
Gal-9-treated emphysema mice was significantly lower than that of PBS-treated
emphysema mice (66.1 +/- 3.3 MUm vs. 118.8 +/- 14.8 MUm, respectively; p < 0.01).
Gal-9 decreased the number of neutrophils and levels of MMP-9, MMP-2 and tissue
inhibitor of metalloproteinases (TIMP)-1 in the BALF. The number of neutrophils
in the BALF correlated significantly with MMPs levels. Interestingly, Gal-9
pretreatment in vitro inhibited the chemotactic activity of neutrophils and MMP-9
production from neutrophils. Furthermore, in Gal-9-deficient mice, PPE-induced
emphysema progressed significantly compared with that in wild-type (WT) mice
(108.7 +/- 6.58 MUm vs. 77.19 +/- 6.97 MUm, respectively; p < 0.01). CONCLUSIONS:
These results suggest that Gal-9 protects PPE-induced inflammation and emphysema
by inhibiting the infiltration of neutrophils and decreasing MMPs levels.
Exogenous Gal-9 could be a potential therapeutic agent for COPD.
PMID- 28704476
TI - Hierarchical trie packet classification algorithm based on expectation
maximization clustering.
AB - With the development of computer network bandwidth, packet classification
algorithms which are able to deal with large-scale rule sets are in urgent need.
Among the existing algorithms, researches on packet classification algorithms
based on hierarchical trie have become an important packet classification
research branch because of their widely practical use. Although hierarchical trie
is beneficial to save large storage space, it has several shortcomings such as
the existence of backtracking and empty nodes. This paper proposes a new packet
classification algorithm, Hierarchical Trie Algorithm Based on Expectation
Maximization Clustering (HTEMC). Firstly, this paper uses the formalization
method to deal with the packet classification problem by means of mapping the
rules and data packets into a two-dimensional space. Secondly, this paper uses
expectation-maximization algorithm to cluster the rules based on their aggregate
characteristics, and thereby diversified clusters are formed. Thirdly, this paper
proposes a hierarchical trie based on the results of expectation-maximization
clustering. Finally, this paper respectively conducts simulation experiments and
real-environment experiments to compare the performances of our algorithm with
other typical algorithms, and analyzes the results of the experiments. The
hierarchical trie structure in our algorithm not only adopts trie path
compression to eliminate backtracking, but also solves the problem of low
efficiency of trie updates, which greatly improves the performance of the
algorithm.
PMID- 28704477
TI - Comparative phenotypic and functional analysis of migratory dendritic cell
subsets from human oral mucosa and skin.
AB - Antigen exposure to oral mucosa is generally thought to lead to immune tolerance
induction. However, very little is known about the subset composition and
function of dendritic cells (DC) migrating from human oral mucosa. Here we show
that migratory DC from healthy human gingival explants consist of the same
phenotypic subsets in the same frequency distribution as DC migrating from human
skin. The gingival CD1a+ Langerhans cell and interstitial DC subsets lacked CXCR4
expression in contrast to their cutaneous counterparts, pointing to different
migration mechanisms, consistent with previous observations in constructed skin
and gingival equivalents. Remarkably, without any exogenous conditioning,
gingival explants released higher levels of inflammatory cytokines than human
skin explants, resulting in higher DC migration rates and a superior ability of
migrated DC to prime allogeneic T cells and to induce type-1 effector T cell
differentiation. From these observations we conclude that rather than an
intrinsic ability to induce T cell tolerance, DC migrating from oral mucosa may
have a propensity to induce effector T cell immunity and maintain a high state of
alert against possible pathogenic intruders in the steady state. These findings
may have implications for oral immunization strategies.
PMID- 28704478
TI - Involvement of community pharmacists in public health priorities: A multi-center
descriptive survey in Ethiopia.
AB - Located in the heart of the community and widely distributed geographically,
community pharmacies provide a platform for a more proactive involvement in
public health services. So far, little information has been gathered in Ethiopia
on community pharmacists' level of involvement in public health services. The aim
of the present study was, therefore, to document the level of involvement of
community pharmacy professionals in the provision of public health services and
the barriers to such involvement. This study employed a self-administered
questionnaire based survey, which asked participants to indicate their frequency
and level of involvement in providing public health services and their perceived
barriers in providing such services. Surveys were undertaken from May to July,
2016 with 472 community pharmacy professionals working in community pharmacies in
six cities of Amhara regional state of Ethiopia: Debre Markos, Gondar, Dessie,
Bahir Dar, Woldya and Debre Birhan. Among 472 community pharmacy professionals
approached, 412 (233 pharmacists and 179 pharmacy technicians) completed the
survey with a response rate of 87.3%. Most respondents reported as being either
"not at all involved" or "little involved" in counselling on smoking cessation
(79.3%), and screening for hypertension (86.9%), diabetes (89.5%), and
dyslipidemia (88.9%). On the other hand, they reported a higher level of
involvement in the management and screening of infectious diseases (72.8%) and
counseling with partners when initiating treatment for sexually transmitted
diseases (68.9%). Lack of knowledge or clinical skills and lack of personnel or
resources were the most commonly reported barrier for expanding such services.
This survey revealed a low level of involvement of community pharmacists in
public health services. In order to better integrate community pharmacies into
future public health programs and optimize the contribution of community pharmacy
professionals, interventions should focus on overcoming the identified barriers.
PMID- 28704479
TI - Dynamic changes in Bach1 expression in the kidney of rhabdomyolysis-associated
acute kidney injury.
AB - Free heme, a pro-oxidant released from myoglobin, is thought to contribute to the
pathogenesis of rhabdomyolysis-associated acute kidney injury (RM-AKI), because
renal overexpression of heme oxygenase-1 (HO-1), the rate-limiting enzyme in heme
catabolism, confers protection against RM-AKI. BTB and CNC homology 1 (Bach1) is
a heme-responsive transcription factor that represses HO-1. Here, we examined the
changes with time in the gene expression of Bach1, HO-1, and delta
aminolevulinate synthase (ALAS1, a heme biosynthetic enzyme) in the rat kidney
using an RM-AKI model induced by the injection of 50% glycerol (10 mL/kg body
weight) into bilateral limbs. We also examined the protein expression of Bach1 in
the nucleus and cytosol, and HO-1 in the rat kidney. Glycerol treatment induced
significant elevation of serum creatinine kinase and aspartate aminotransferase
levels followed by the marked elevation of serum blood urea nitrogen and
creatinine levels, which caused serious damage to renal tubules. Following
glycerol treatment, HO-1 mRNA and protein levels were significantly up-regulated,
while ALAS1 mRNA expression was down-regulated, suggesting an increase in the
free renal heme concentration. The Bach1 mRNA level was drastically increased 3 h
after glycerol treatment, and the increased level was maintained for 12 h.
Nuclear Bach1 protein levels were significantly decreased 3 h after treatment.
Conversely, cytosolic Bach1 protein levels abruptly increased after 6 h. In
conclusion, we demonstrate the dynamic changes in Bach1 expression in a rat model
of RM-AKI. Our findings suggest that the increase in Bach1 mRNA and cytosolic
Bach1 protein expression may reflect de novo Bach1 protein synthesis to
compensate for the depletion of nuclear Bach1 protein caused by the induction of
HO-1 by free heme.
PMID- 28704480
TI - Host niche may determine disease-driven extinction risk.
AB - The fungal pathogen Batrachochytrium dendrobatidis (Bd) drives declines and
extinctions in amphibian communities. However, not all regions and species are
equally affected. Here, we show that association with amphibian aquatic habitat
types (bromeliad phytotelmata versus stream) across Central America results in
the odds of being threatened by Bd being five times higher in stream
microhabitats. This differential threat of Bd was supported in our study by a
significantly lower prevalence of Bd in bromeliad-associated amphibian species
compared to riparian species in Honduran cloud forests. Evidence that the
bromeliad environment is less favorable for Bd transmission is exemplified by
significantly less suitable physicochemical conditions and higher abundance of Bd
ingesting micro-eukaryotes present in bromeliad water. These factors may inhibit
aquatic Bd zoospore survival and the development of an environmental reservoir of
the pathogen. Bromeliad phytotelmata thus may act as environmental refuges from
Bd, which contribute to protecting associated amphibian communities against
chytridiomycosis-driven amphibian declines that threaten the nearby riparian
communities.
PMID- 28704481
TI - Renal auto-transplantation promotes cortical microvascular network remodeling in
a preclinical porcine model.
AB - The vascular network is a major target of ischemia-reperfusion, but has been
poorly investigated in renal transplantation. The aim of this study was to
characterize the remodeling of the renal vascular network that follows ischemia
reperfusion along with the most highly affected cortex section in a preclinical
renal transplantation model. There were two experimental groups. The first was a
grafted kidney group consisting of large white pigs for which the left kidney was
harvested, cold flushed, preserved for 24 h in the University of Wisconsin's
preservation solution, and then auto-transplanted (n = 5); the right kidney was
removed to mimic the situation of human kidney transplantation. The second group
(uni-nephrectomized kidney group) consisted of animals that underwent only right
nephrectomy, but not left renal transplantation (n = 5). Three months after
autotransplantation, the kidneys were studied by X-ray microcomputed tomography.
Vessel morphology and density and tortuosity of the network were analyzed using a
3D image analysis method. Cortical blood flow was determined by laser doppler
analysis and renal function and tissue injury assessed by plasma creatinine
levels and histological analysis. Renal ischemia-reperfusion led to decreased
vascular segment volume associated with fewer vessels of less than 30 MUm,
particularly in the inner cortex:0.79 +/- 0.54% in grafted kidneys vs. 7.06 +/-
1.44% in uni-nephrectomized kidneys, p < 0.05. Vessels showed higher connectivity
throughout the cortex (the arborescence factor of the whole cortex was less in
grafted than uni-nephrectomized kidneys 0.90 +/- 0.04 vs. 1.07 +/- 0.05, p <
0.05, with an increase in the number of bifurcations). Furthermore, cortical
blood flow decreased early in kidney grafts and remained low three months after
auto-transplantation. The decrease in microvasculature correlated with a
deterioration of renal function, proteinuria, and tubular dysfunction, and was
associated with the development of fibrous tissue. This work provides new
evidence concerning the impact of ischemia-reperfusion injuries on the spectrum
of renal vascular diseases and could potentially guide future therapy to preserve
microvessels in transplantation ischemia-reperfusion injury.
PMID- 28704482
TI - Proteomic identification of proteins differentially expressed following
overexpression of hTERT (human telomerase reverse transcriptase) in cancer cells.
AB - Reverse transcriptase activity of telomerase adds telomeric repeat sequences at
extreme ends of the newly replicated chromosome in actively dividing cells.
Telomerase expression is not detected in terminally differentiated cells but is
noticeable in 90% of the cancer cells. hTERT (human telomerase reverse
transcriptase) expression seems to promote invasiveness of cancer cells. We here
present proteomic profiles of cells overexpressing or knocked down for hTERT.
This study also attempts to find out the potential interacting partners of hTERT
in cancer cell lines. Two-dimensional gel electrophoresis (2-DE) of two different
cell lines U2OS (a naturally hTERT negative cell line) and HeLa revealed
differential expression of proteins in hTERT over-expressing cells. In U2OS cell
line 28 spots were picked among which 23 spots represented upregulated and 5
represented down regulated proteins. In HeLa cells 21 were upregulated and 2 were
down regulated out of 23 selected spots under otherwise identical experimental
conditions. Some heat shock proteins viz. Hsp60 and Hsp70 and GAPDH, which is a
housekeeping gene, were found similarly upregulated in both the cell lines. The
upregulation of these proteins were further confirmed at RNA and protein level by
real-time PCR and western blotting respectively.
PMID- 28704483
TI - A anti-jamming method for satellite navigation system based on multi-objective
optimization technique.
AB - In this paper, an anti-jamming method, which turns the single objective
optimization problem into a multi-objective optimization problem by utilizing 2
norm, is proposed. The proposed jamming suppression method can reduce the wide
nulls and wrong nulls problems, which are generated by the common adaptive
nulling methods. Therefore a better signal-noise-ratio (SNR) can be achieved,
especially when the jammers are close to satellite signals. It can also improve
the robustness of the algorithm. The effectiveness of the proposed method is
evaluated by simulation and practical outdoor experiments with the GPS L1 band
C/A signals. The experimental results show that with the dedicated method, the
nulls targeting at the corresponding jammers become narrower and the wrong nulls
can be eliminated.
PMID- 28704484
TI - Apoptosis by [Pt(O,O'-acac)(gamma-acac)(DMS)] requires PKC-delta mediated p53
activation in malignant pleural mesothelioma.
AB - Mesothelioma cancer cells have epithelioid or sarcomatoid morphology. The worst
prognosis is associated with sarcomatoid phenotype and resistance to therapy is
affected by cells heterogeneity. We recently showed that in ZL55 mesothelioma
cell line of epithelioid origin [Pt(O,O'-acac)(gamma-acac)(DMS)] (Ptac2S) has an
antiproliferative effect in vitro and in vivo. Aim of this work was to extend the
study on the effects of Ptac2S on ZL34 cell line, representative of sarcomatoid
mesothelioma. ZL34 cells were used to assay the antitumor activity of Ptac2S in a
mouse xenograft model in vivo. Then, both ZL34 and ZL55 cells were used in order
to assess the involvement of p53 protein in (a) the processes underlying the
sensitivity to chemotherapy and (b) the activation of various transduction
proteins involved in apoptosis/survival processes. Ptac2S increases ZL34 cell
death in vivo compared with cisplatin and, in vitro, Ptac2S was more efficacious
than cisplatin in inducing apoptosis. In Ptac2S-treated ZL34 and ZL55 cells, p53
regulated gene products of apoptotic BAX and anti-apoptotic Bcl-2 proteins via
transcriptional activation. Ptac2S activated PKC-delta and PKC-epsilon; their
inhibition by PKC-siRNA decreased the apoptotic death of cells. PKC-delta was
responsible for JNK1/2 activation that has a role in p53 activation. In addition,
PKC-epsilon activation provoked phosphorylation of p38MAPK, concurring to
apoptosis. In ZL34 cells, Ptac2S also activated PKC-alpha thus provoking ERK1/2
activation; inhibition of PKC-alpha, or ERK1/2, increased Ptac2S cytotoxicity.
Results confirm that Ptac2S is a promising therapeutic agent for malignant
mesothelioma, giving a substantial starting point for its further validation.
PMID- 28704485
TI - The role of proximal body information on anticipatory judgment in tennis using
graphical information richness.
AB - OBJECTIVE: Recent studies have reported that skilled tennis players are likely to
use proximal body information for anticipating the direction of their opponent's
forehand shot. However, in these studies, the visual stimuli did not include
visual information about the ball. Skilled players may have used proximal
information owing to the lack of distal information. To address this issue, we
developed a novel methodological approach using computer graphics (CG) images in
which the entire body was presented by a combination of point-light display
(i.e., poor graphical information, PLD) and polygons (i.e., rich graphical
information). Using our novel methodological approach, we examined whether
skilled tennis players use proximal body information when anticipating shot
directions. METHODS AND RESULTS: Fifteen skilled tennis players and fifteen
novice players tried to anticipate shot directions by observing four CG forehand
strokes (ALPOL: all body parts were represented with polygon; RAPLD: racket and
arm were represented with PLD; BOPLD: body parts without racket and arm were
represented with PLD; and ALPLD: all body parts were represented with PLD). Our
intention in creating CG models with such combinations (i.e., RAPLD and BOPLD)
was that because of the richer graphical information provided by polygons
compared to PLD, the participant's anticipatory judgment would be influenced more
by body parts expressed with polygons. The results showed that for skilled
players, anticipatory judgment was more accurate when they observed RAPLD than
when they observed BOPLD and ALPLD. In contrast, for novice players, there were
no differences in the accuracy of anticipatory judgments with the four CG models.
CONCLUSIONS: Only skilled players made more accurate anticipatory judgments when
body regions were expressed with rich graphical information, and the racket and
arm were expressed with poor graphical information. These suggest that skilled
players used proximal information to effectively anticipate shot directions.
PMID- 28704486
TI - A common bottlenose dolphin (Tursiops truncatus) prey handling technique for
marine catfish (Ariidae) in the northern Gulf of Mexico.
AB - Few accounts describe predator-prey interactions between common bottlenose
dolphins (Tursiops truncatus Montagu 1821) and marine catfish (Ariopsis felis
Linnaeus 1766, Bagre marinus Mitchill 1815). Over the course of 50,167 sightings
of bottlenose dolphin groups in Mississippi Sound and along the Florida coast of
the Gulf of Mexico, severed catfish heads were found floating and exhibiting
movements at the surface in close proximity to 13 dolphin groups that
demonstrated feeding behavior. These observations prompted a multi-disciplinary
approach to study the predator-prey relationship between bottlenose dolphins and
marine catfish. A review was conducted of bottlenose dolphin visual survey data
and dorsal fin photographs from sightings where severed catfish heads were
observed. Recovered severed catfish heads were preserved and studied, whole
marine catfish were collected and examined, and stranding network pathology
reports were reviewed for references to injuries related to fish spines.
Photographic identification analysis confirms eight dolphins associated with
severed catfish heads were present in three such sightings across an
approximately 350 km expanse of coast between the Mississippi Sound and Saint
Joseph Bay, FL. An examination of the severed catfish heads indicated interaction
with dolphins, and fresh-caught whole hardhead catfish (A. felis) were examined
to estimate the presumed total length of the catfish before decapitation. Thirty
eight instances of significant trauma or death in dolphins attributed to
ingesting whole marine catfish were documented in stranding records collected
from the southeastern United States of America. Bottlenose dolphins typically
adhere to a ram-feeding strategy for prey capture followed by whole prey
ingestion; however, marine catfish skull morphology may pose a consumption hazard
due to rigid spines that can puncture and migrate through soft tissue, prompting
a prey handling technique for certain dolphins, facilitating consumption of the
posterior portion of the fish without the head.
PMID- 28704487
TI - Assessment of peak oxygen uptake during handcycling: Test-retest reliability and
comparison of a ramp-incremented and perceptually-regulated exercise test.
AB - PURPOSE: To examine the reliability of a perceptually-regulated maximal exercise
test (PRETmax) to measure peak oxygen uptake ([Formula: see text]) during
handcycle exercise and to compare peak responses to those derived from a ramp
incremented protocol (RAMP). METHODS: Twenty recreationally active individuals
(14 male, 6 female) completed four trials across a 2-week period, using a
randomised, counterbalanced design. Participants completed two RAMP protocols (20
W.min-1) in week 1, followed by two PRETmax in week 2, or vice versa. The PRETmax
comprised five, 2-min stages clamped at Ratings of Perceived Exertion (RPE) 11,
13, 15, 17 and 20. Participants changed power output (PO) as often as required to
maintain target RPE. Gas exchange variables (oxygen uptake, carbon dioxide
production, minute ventilation), heart rate (HR) and PO were collected
throughout. Differentiated RPE were collected at the end of each stage throughout
trials. RESULTS: For relative [Formula: see text], coefficient of variation (CV)
was equal to 4.1% and 4.8%, with ICC(3,1) of 0.92 and 0.85 for repeated measures
from PRETmax and RAMP, respectively. Measurement error was 0.15 L.min-1 and 2.11
ml.kg-1.min-1 in PRETmax and 0.16 L.min-1 and 2.29 ml.kg-1.min-1 during RAMP for
determining absolute and relative [Formula: see text], respectively. The
difference in [Formula: see text] between PRETmax and RAMP was tending towards
statistical significance (26.2 +/- 5.1 versus 24.3 +/- 4.0 ml.kg-1.min-1, P =
0.055). The 95% LoA were -1.9 +/- 4.1 (-9.9 to 6.2) ml.kg-1.min-1. CONCLUSION:
The PRETmax can be used as a reliable test to measure [Formula: see text] during
handcycle exercise in recreationally active participants. Whilst PRETmax tended
towards significantly greater [Formula: see text] values than RAMP, the
difference is smaller than measurement error of determining [Formula: see text]
from PRETmax and RAMP.
PMID- 28704488
TI - Soluble ST2 does not change cardiovascular risk prediction compared to cardiac
troponin T in kidney transplant candidates.
AB - BACKGROUND: Solubility of Tumorigenicity 2 (sST2) is a novel biomarker that
better stratifies risk of cardiovascular events (CVE) compared to cardiac
troponin T(cTnT) in heart failure. We assessed the association of sST2 with the
composite outcome of CVE and/or mortality compared to cTnT in kidney transplant
candidates. METHODS: 200 kidney transplant candidates between 2010 and 2013 were
included. Elevated sST2 was defined as >=30ng/ml, cTnT>=0.01 ng/ml. RESULTS:
Median age 53 (interquartile range (IQR) 42-61) years, 59.7% male and 82.0%
white. 33.5% had history of CVE, 42.5% left ventricular hypertrophy (LVH) and
15.6% positive cardiac stress test. Elevated sST2 correlated with male gender,
history of prior-transplants, CVE, positive stress test, LVH, elevated cTnT,
anemia, hyperphosphatemia, increased CRP and non-transplanted status. Male
gender, history of CVE and LVH were independent determinants of sST2. During 28
months (IQR 25.3-30), 7.5% died, 13.0% developed CVE and 19.0% developed the
composite outcome. Elevated sST2 was associated with the composite outcome
(hazard ratio = 1.76, CI 1.06-2.73, p = 0.029) on univariate analysis but not
after adjusting for age, diabetes and cTnT (p = 0.068). sST2 did not change the
risk prediction model for composite outcome after including age, diabetes, prior
history of CVE and elevated cTnT. CONCLUSIONS: Increased sST2 level is
significantly associated with variables associated with CVE in kidney transplant
candidates. sST2 was associated with increased risk of the composite outcome of
CVE and/or death but not independent of cTnT. Larger studies are needed to
confirm these findings and determine whether sST2 has added value in CV risk
stratification in this cohort of patients.
PMID- 28704489
TI - A two-stage approach to the depot shunting driver assignment problem with
workload balance considerations.
AB - Due to its environmentally sustainable and energy-saving characteristics, railway
transportation nowadays plays a fundamental role in delivering passengers and
goods. Emerged in the area of transportation planning, the crew (workforce)
sizing problem and the crew scheduling problem have been attached great
importance by the railway industry and the scientific community. In this paper,
we aim to solve the two problems by proposing a novel two-stage optimization
approach in the context of the electric multiple units (EMU) depot shunting
driver assignment problem. Given a predefined depot shunting schedule, the first
stage of the approach focuses on determining an optimal size of shunting drivers.
While the second stage is formulated as a bi-objective optimization model, in
which we comprehensively consider the objectives of minimizing the total walking
distance and maximizing the workload balance. Then we combine the normalized
normal constraint method with a modified Pareto filter algorithm to obtain Pareto
solutions for the bi-objective optimization problem. Furthermore, we conduct a
series of numerical experiments to demonstrate the proposed approach. Based on
the computational results, the regression analysis yield a driver size predictor
and the sensitivity analysis give some interesting insights that are useful for
decision makers.
PMID- 28704490
TI - The synthetic killer peptide KP impairs Candida albicans biofilm in vitro.
AB - Candida albicans is a commensal organism, commonly inhabiting mucosal surfaces of
healthy individuals, as a part of the resident microbiota. However, in
susceptible hosts, especially hospitalized and/or immunocompromised patients, it
may cause a wide range of infections. The presence of abiotic substrates, such as
central venous or urinary catheters, provides an additional niche for Candida
attachment and persistence, particularly via biofilm development. Furthermore,
Candida biofilm is poorly susceptible to most antifungals, including azoles. Here
we investigated the effects of a synthetic killer peptide (KP), known to be
active in vitro, ex vivo and/or in vivo against different pathogens, on C.
albicans biofilm. Together with a scrambled peptide used as a negative control,
KP was tested against Candida biofilm at different stages of development. A
reference strain, two fluconazole-resistant and two fluconazole-susceptible C.
albicans clinical isolates were used. KP-induced C. albicans oxidative stress
response and membrane permeability were also analysed. Moreover, the effect of KP
on transcriptional profiles of C. albicans genes involved in different stages of
biofilm development, such as cell adhesion, hyphal development and extracellular
matrix production, was evaluated. Our results clearly show that the treatment
with KP strongly affected the capacity of C. albicans to form biofilm and
significantly impairs preformed mature biofilm. KP treatment resulted in an
increase in C. albicans oxidative stress response and membrane permeability;
also, biofilm-related genes expression was significantly reduced. Comparable
inhibitory effects were observed in all the strains employed, irrespective of
their resistance or susceptibility to fluconazole. Finally, KP-mediated
inhibitory effects were observed also against a catheter-associated C. albicans
biofilm. This study provides the first evidence on the KP effectiveness against
C. albicans biofilm, suggesting that KP may be considered as a potential novel
tool for treatment and prevention of biofilm-related C. albicans infections.
PMID- 28704491
TI - Phyto-toponyms of Arbutus unedo L. and their distribution in Sardinia (Italy).
AB - The study shows the results of an inventory of place names connected to Arbutus
unedo L., a Mediterranean species, widespread throughout Sardinia. The main aim
was to compare the past distribution of place names, referring to the strawberry
tree, to the current distribution of the species on the island. In addition, we
investigated the meaning and the diversity of these local place names in the
various communities. The result was a collection of 432 phyto-toponyms. 248 of
them were used for an analysis of their distribution in the habitats, indicated
on the Map of the Nature System in Sardinia, defined on the basis of the current
vegetation typology. The persistence of the species in the various habitats was
either confirmed or negated with in site investigations and interviews. 47.5% of
municipalities have place names related to the strawberry tree. Of the 248 phyto
toponyms, 127 fall in the habitats where the species currently persists proving a
correspondence between their regional distribution and the current distribution
of the species. The remaining 121 phyto-toponyms fall in habitats where the
strawberry tree is currently absent. Most of them are found in man-made habitats
where man has transformed the forest cover which previously included the
strawberry tree. This study also contributes to promoting and conserving the
linguistic heritage of local communities.
PMID- 28704492
TI - Cerebrospinal fluid matrix metalloproteinase 9 levels, blood-brain barrier
permeability, and treatment outcome in tuberculous meningitis.
AB - OBJECTIVES: Tuberculous meningitis is characterized by elevated levels of matrix
metalloproteinase 9 (MMP9) in the cerebrospinal fluid (CSF). However, it is
unclear whether elevated MMP9 levels are associated with poor treatment outcome.
We tested the hypothesis that pretreatment MMP9 levels in the CSF would be higher
in tuberculous meningitis patients experiencing a poor treatment outcome.
METHODS: We prospectively assessed the treatment outcome in a consecutive sample
of human immunodeficiency virus-negative patients with tuberculous meningitis. We
defined good outcome as survival without severe neurological disability (modified
Rankin scale scores 0-2). We estimated levels of MMP9 and its tissue inhibitor
(TIMP1) on pretreatment CSF samples. We used albumin index to assess blood-brain
barrier permeability. RESULTS: We studied 40 patients (23 males [58%]) with
tuberculous meningitis. Sixteen patients (40%) had stage 3 disease. On follow-up,
18 (45%) patients had a poor treatment outcome-15 patients died and 3 had severe
neurological disability. Pretreatment MMP9 levels were not associated with
treatment outcome (median [interquartile range], 254 [115-389] vs. 192 [60-383]
ng/mL in good vs. poor outcome groups; P = 0.693). MMP9 levels did not correlate
with the albumin index (Spearman's rho = 0.142; P = 0.381). However, MMP9 levels
significantly correlated with CSF glucose levels (rho = -0.419; P = 0.007) and
admission Glasgow coma scale score (rho = 0.324; P = 0.032). Likewise, TIMP1
levels also did not differ by treatment outcome (1239 [889-1511] vs. 1522 [934
1949] ng/mL; P = 0.201). MMP9/TIMP1 ratio that reflects net proteolytic activity
was also not different between the two groups (0.191 [0.107-0.250] vs. 0.163
[0.067-0.34]; P = 0.625). CONCLUSION: Our findings do not support the hypothesis
that pretreatment levels of MMP9 would be higher in tuberculous meningitis
patients experiencing a poor treatment outcome. Further, MMP9 levels in the CSF
did not correlate with blood-brain barrier permeability in patients with
tuberculous meningitis.
PMID- 28704493
TI - Evaluating the effect of mutations and ligand binding on transthyretin
homotetramer dynamics.
AB - Native transthyretin (TTR) homotetramer dissociation is the first step of the
fibrils formation process in amyloid disease. A large number of specific point
mutations that destabilize TTR quaternary structure have shown pro-amyloidogenic
effects. Besides, several compounds have been proposed as drugs in the therapy of
TTR amyloidosis due to their TTR tetramer binding affinities, and therefore,
contribution to its integrity. In the present paper we have explored key
positions sustaining TTR tetramer dynamical stability. We have identified
positions whose mutations alter the most the TTR tetramer equilibrium dynamics
based on normal mode analysis and their response to local perturbations. We have
found that these positions are mostly localized at beta-strands E and F and EF
loop. The monomer-monomer interface is pointed out as one of the most vulnerable
regions to mutations that lead to significant changes in the TTR-tetramer
equilibrium dynamics and, therefore, induces TTR amyloidosis. Besides, we have
found that mutations on residues localized at the dimer-dimer interface and/or at
the T4 hormone binding site destabilize the tetramer more than the average.
Finally, we were able to compare several compounds according to their effect on
vibrations associated to the ligand binding. Our ligand comparison is discussed
and analyzed in terms of parameters and measurements associated to TTR-ligand
binding affinities and the stabilization of its native state.
PMID- 28704494
TI - Effects of a multidisciplinary weight loss intervention in overweight and obese
children and adolescents: 11 years of experience.
AB - AIMS: To evaluate the effects of an outpatient multidisciplinary weight loss
intervention in reducing body mass index (BMI) in children and adolescents
suffering overweight and obesity, changes in A Body Shape Index (ABSI, waist
circumference normalized to height and weight) and Hip Index (HI, normalized hip
circumference) during treatment and correlation between the ABSI and HI with
change in BMI z score. METHODS: We analyze anthropometric data from pediatric
patients affected by overweight and obesity aged 2 to 18 years old who entered
our multidisciplinary weight loss intervention, which included medical,
psychological and nutritional sessions, from January 1st 2006 to December 31st
2016. Lifestyle modification counselling was delivered. Follow-up visits were
planned every month for 3 months and subsequently every 2-4 months. BMI, ABSI,
and HI were converted to z scores using age and sex specific population normals.
RESULTS: 864 patients entered our intervention. 453 patients (208 males), mean
age 11.2 +/-3.1 years, 392 with obesity (86%, z-BMI 2.90 +/-0.80 SD) and 61
patients with overweight (z-BMI 1.73+/-0.21 SD) attended at least 1 follow-up
visit. The mean number of visits was 3.5 (+/- 1.8 SD) in overweight subjects and
3.9 (+/-2.2 SD) in ones with obesity. At the last attended follow-up visit (at 16
+/- 12 months SD) we observed a reduction in mean z-BMI in patients with obesity
(to 2.52 +/-0.71 SD) and patients with overweight (to 1.46 +/-0.5 SD). Most
patients (80.8%) reduced their BMI z scores. Mean ABSI and HI z scores showed no
significant change. 78/392 patients (19.8%) recovered from obese to overweight,
5/392 (1.2%) from obese to normal weight. The recovery rate from overweight to
normal weight was 13.1%. In a multivariate model, initial BMI z score and number
of follow-up visits were significant predictors of weight change, while age, sex,
ABSI, and HI were not significant predictors. CONCLUSIONS: Patients affected by
overweight and obesity involved in a multidisciplinary weight loss intervention
reduced their mean BMI z score, while ABSI and HI were stable. Weight loss was
not predicted by initial ABSI or HI. More visits predict more weight loss, but
dropout rates are high. The great majority of patients leave the weight
management program before having normalized their BMI.
PMID- 28704495
TI - Space-time analysis of pneumonia hospitalisations in the Netherlands.
AB - Community acquired pneumonia is a major global public health problem. In the
Netherlands there are 40,000-50,000 hospital admissions for pneumonia per year.
In the large majority of these hospital admissions the etiologic agent is not
determined and a real-time surveillance system is lacking. Localised and temporal
increases in hospital admissions for pneumonia are therefore only detected
retrospectively and the etiologic agents remain unknown. Here, we perform spatio
temporal analyses of pneumonia hospital admission data in the Netherlands. To
this end, we scanned for spatial clusters on yearly and seasonal basis, and
applied wavelet cluster analysis on the time series of five main regions. The
pneumonia hospital admissions show strong clustering in space and time
superimposed on a regular yearly cycle with high incidence in winter and low
incidence in summer. Cluster analysis reveals a heterogeneous pattern, with most
significant clusters occurring in the western, highly urbanised, and in the
eastern, intensively farmed, part of the Netherlands. Quantitatively, the
relative risk (RR) of the significant clusters for the age-standardised incidence
varies from a minimum of 1.2 to a maximum of 2.2. We discuss possible underlying
causes for the patterns observed, such as variations in air pollution.
PMID- 28704496
TI - Latitudinal cogradient variation of development time and growth rate and a
negative latitudinal body weight cline in a widely distributed cabbage beetle.
AB - The evolutionary and phenotypic responses to environmental gradients are often
assumed to be the same, a phenomenon known as "cogradient variation". However,
only a few insect species display cogradient variation in physiological traits
along a latitudinal gradient. We found evidence for such a response in the
examination of the life history traits of the cabbage beetle Colaphellus bowringi
from 6 different geographical populations at 16, 19, 22, 24, 26 and 28 degrees C.
Our results showed that larval and pupal development times significantly
decreased as rearing temperature increased, and that growth rates were positively
correlated with temperature. Body weight tended to decrease with increasing
temperature, consistent with the general pattern in ectothermic animals. Larval
development time was positively correlated with latitude, whereas the growth rate
decreased as latitude increased, showing an example of latitudinal cogradient
variation. Body weight significantly decreased with increasing latitude in a
stepwise manner, showing a negative latitudinal body weight cline. Females were
significantly larger than males, consistent with the female biased sex dimorphism
in insects. Body weight tended to decrease with increasing rearing temperature,
whereas the differences in sexual size dimorphism (SSD) tended to decrease with
increasing body weight, which biased our results toward acceptance of Rensch's
rule. We found that weight loss was an important regulator of SSD, and because
male pupae lost significantly more weight at metamorphosis than female pupae, SSD
was greater in adults than in pupae. Overall, our data provide a new example that
a latitudinal cogradient variation in physiological traits is associated with a
negative latitudinal body weight cline.
PMID- 28704497
TI - Genetic mapping of the LOBED LEAF 1 (ClLL1) gene to a 127.6-kb region in
watermelon (Citrullus lanatus L.).
AB - The lobed leaf character is a unique morphologic trait in crops, featuring many
potential advantages for agricultural productivity. Although the majority of
watermelon varieties feature lobed leaves, the genetic factors responsible for
lobed leaf formation remain elusive. The F2:3 leaf shape segregating population
offers the opportunity to study the underlying mechanism of lobed leaf formation
in watermelon. Genetic analysis revealed that a single dominant allele
(designated ClLL1) controlled the lobed leaf trait. A large-sized F3:4 population
derived from F2:3 individuals was used to map ClLL1. A total of 5,966 reliable
SNPs and indels were identified genome-wide via a combination of BSA and RNA-seq.
Using the validated SNP and indel markers, the location of ClLL1 was narrowed
down to a 127.6-kb region between markers W08314 and W07061, containing 23
putative ORFs. Expression analysis via qRT-PCR revealed differential expression
patterns (fold-changes above 2-fold or below 0.5-fold) of three ORFs (ORF3,
ORF11, and ORF18) between lobed and non-lobed leaf plants. Based on gene
annotation and expression analysis, ORF18 (encoding an uncharacterized protein)
and ORF22 (encoding a homeobox-leucine zipper-like protein) were considered as
most likely candidate genes. Furthermore, sequence analysis revealed no
polymorphisms in cDNA sequences of ORF18; however, two notable deletions were
identified in ORF22. This study is the first report to map a leaf shape gene in
watermelon and will facilitate cloning and functional characterization of ClLL1
in future studies.
PMID- 28704498
TI - Biological control of Heterodera glycines by spore-forming plant growth-promoting
rhizobacteria (PGPR) on soybean.
AB - Heterodera glycines, the soybean cyst nematode, is the most economically
important plant-parasitic nematode on soybean production in the U.S. The
objectives of this study were to evaluate the potential of plant growth-promoting
rhizobacteria (PGPR) strains for mortality of H. glycines J2 in vitro and for
reducing nematode population density on soybean in greenhouse, microplot, and
field trials. The major group causing mortality to H. glycines in vitro was the
genus Bacillus that consisted of 92.6% of the total 663 PGPR strains evaluated.
The subsequent greenhouse, microplot, and field trials indicated that B.
velezensis strain Bve2 consistently reduced H. glycines cyst population density
at 60 DAP. Bacillus mojavensis strain Bmo3 suppressed H. glycines cyst and total
H. glycines population density under greenhouse conditions. Bacillus safensis
strain Bsa27 and Mixture 1 (Bve2 + Bal13) reduced H. glycines cyst population
density at 60 DAP in the field trials. Bacillus subtilis subsp. subtilis strains
Bsssu2 and Bsssu3, and B. velezensis strain Bve12 increased early soybean growth
including plant height and plant biomass in the greenhouse trials. Bacillus
altitudinis strain Bal13 increased early plant growth on soybean in the
greenhouse and microplot trials. Mixture 2 (Abamectin + Bve2 + Bal13) increased
early plant growth in the microplot trials at 60 DAP, and also enhanced soybean
yield at harvest in the field trials. These results demonstrated that individual
PGPR strains and mixtures can reduce H. glycines population density in the
greenhouse, microplot, and field conditions, and increased yield of soybean.
PMID- 28704499
TI - The low expression of miR-451 predicts a worse prognosis in non-small cell lung
cancer cases.
AB - PURPOSE: miR-451 is a tumor suppressive microRNA with several target genes,
including Macrophage migration inhibitory factor (MIF). As little is known about
the expression and clinicopathological significance of mir-451 in NSCLC, we
performed a clinicopathological study of 370 NSCLC cases to clarify them. Cell
biological experiments were also performed on NSCLC cell lines to confirm the
tumor-suppressive role of miR-451 and whether or not MIF is targeted by miR-451.
METHODS: We analyzed 370 NSCLC cases for the miR-451 expression by quantitative
real-time polymerase chain reaction and the MIF expression by
immunohistochemistry. Eighty-four background lung tissue samples were also
evaluated for the miR-451 expression. The clinicopathological and genetic factors
surveyed were the disease-free survival, smoking status, histological type,
disease stage, EGFR gene mutations and ALK rearrangements. In 286 adenocarcinoma
cases, the invasive status (adenocarcinoma in situ, minimally invasive
adenocarcinoma and invasive adenocarcinoma) was also evaluated. Five NSCLC cell
lines (H23, H441, H522, H1703, and H1975) were cultured and evaluated for their
miR-451 and MIF expression. The cell lines with lower miR-451 and higher MIF
expressions were then selected and transfected with miR-451-mimic to observe its
effects on MIF expression, Akt and Erk status, cell proliferation, and cell
migration. RESULTS: The miR-451 expression was down-regulated in cancer tissues
compared with background lung tissues (P<0.0001). Factors such as advanced
disease stage, positive pleural invasion and nodal status and being a smoker were
significantly correlated with a lower expression of miR-451 (P<0.05 each), while
EGFR gene mutations and ALK rearrangements were not. In adenocarcinoma, invasive
and minimally invasive adenocarcinoma showed lower expression of miR-451 than
adenocarcinoma in situ (P<0.0005, respectively). A survival analysis showed that
a lower expression of miR-451 was an independent predictor of a poor prognosis
for NSCLC (P<0.05). The MIF expression was inversely correlated with the miR-451
expression. Out of 5 NSCLC cell lines examined, H441 and H1975 showed higher MIF
and lower miR-451 expressions. After the transfection of miR-451-mimic, the MIF
expression and phosphorylated Akt expression of these cell lines was suppressed,
as were cell proliferation and cell migration. CONCLUSION: This
clinicopathological study of 370 NSCLC cases and the cell biological studies of
NSCLC cell lines clarified the tumor-suppressive role of miR-451 and its
prognostic value. We also validated MIF as a target of miR-451 in NSCLC.
PMID- 28704500
TI - Transcriptomic and metabolomic profiles of Chinese citrus fly, Bactrocera minax
(Diptera: Tephritidae), along with pupal development provide insight into
diapause program.
AB - The Chinese citrus fly, Bactrocera minax (Enderlein), is a devastating citrus
pest in Asia. This univoltine insect enters obligatory pupal diapause in each
generation, while little is known about the course and the molecular mechanisms
of diapause. In this study, the course of diapause was determined by measuring
the respiratory rate throughout the pupal stage. In addition, the variation of
transcriptomic and metabolomic profiles of pupae at five developmental stages
(pre-, early-, middle-, late-, and post-diapause) were evaluated by next
generation sequencing technology and 1H nuclear magnetic resonance spectroscopy
(NMR), respectively. A total of 4,808 genes were significantly altered in ten
pairwise comparisons, representing major shifts in metabolism and signal
transduction as well as endocrine system and digestive system. Gene expression
profiles were validated by qRT-PCR analysis. In addition, 48 metabolites were
identified and quantified by 1H NMR. Nine of which significantly contributed to
the variation in the metabolomic profiles, especially proline and trehalose.
Moreover, the samples collected within diapause maintenance (early-, middle-, and
late-diapause) only exhibited marginal transcriptomic and metabolomic variation
with each other. These findings greatly improve our understanding of B. minax
diapause and lay the foundation for further pertinent studies.
PMID- 28704501
TI - Reduced susceptibility of clinical strains of Mycobacterium tuberculosis to
reactive nitrogen species promotes survival in activated macrophages.
AB - BACKGROUND: Drugs such as isoniazid (INH) and pretomanid (PRT), used against
Mycobacterium tuberculosis are active partly through generation of reactive
nitrogen species (RNS). The aim of this study was to explore variability in
intracellular susceptibility to nitric oxide (NO) in clinical strains of M.
tuberculosis. METHOD: Luciferase-expressing clinical M. tuberculosis strains with
or without INH resistance were exposed to RNS donors (DETA/NO and SIN-1) in broth
cultures and bacterial survival was analysed by luminometry. NO-dependent
intracellular killing in a selection of strains was assessed in interferon
gamma/lipopolysaccharide-activated murine macrophages using the NO inhibitor L
NMMA. RESULTS: When M. tuberculosis H37Rv was compared to six clinical isolates
and CDC1551, three isolates with inhA mediated INH resistance showed
significantly reduced NO-susceptibility in broth culture. All strains showed a
variable but dose-dependent susceptibility to RNS donors. Two clinical isolates
with increased susceptibility to NO exposure in broth compared to H37Rv were
significantly inhibited by activated macrophages whereas there was no effect on
growth inhibition when activated macrophages were infected by clinical strains
with higher survival to NO exposure in broth. Furthermore, the most NO-tolerant
clinical isolate showed increased resistance to PRT both in broth culture and the
macrophage model compared to H37Rv in the absence of mutational resistance in
genes associated to reduced susceptibility against PRT or NO. CONCLUSION: In a
limited number of clinical M. tuberculosis isolates we found a significant
difference in susceptibility to NO between clinical isolates, both in broth
cultures and in macrophages. Our results indicate that mycobacterial
susceptibility to cellular host defence mechanisms such as NO need to be taken
into consideration when designing new therapeutic strategies.
PMID- 28704502
TI - Brain natriuretic peptide (BNP) may play a major role in risk stratification
based on cerebral oxygen saturation by near-infrared spectroscopy in patients
undergoing major cardiovascular surgery.
AB - PURPOSE: A previous study reported that low baseline cerebral oxygen saturation
(ScO2) (<=50%) measured with near-infrared spectroscopy was predictive of poor
clinical outcomes after cardiac surgery. However, such findings have not been
reconfirmed by others. We conducted the current study to evaluate whether the
previous findings would be reproducible, and to explore mechanisms underlying the
ScO2-based outcome prediction. METHODS: We retrospectively investigated 573
consecutive patients, aged 20 to 91 (mean +/- standard deviation, 67.1 +/- 12.8)
years, who underwent major cardiovascular surgery. Preanesthetic baseline ScO2,
lowest intraoperative ScO2, various clinical variables, and hospital mortality
were examined. RESULTS: Bivariate regression analyses revealed that baseline ScO2
correlated significantly with plasma brain natriuretic peptide concentration
(BNP), hemoglobin concentration (Hgb), estimated glomerular filtration rate
(eGFR), and left ventricular ejection fraction (LVEF) (p < 0.0001 for each).
Baseline ScO2 correlated with BNP in an exponential manner, and BNP was the most
significant factor influencing ScO2. Logistic regression analyses revealed that
baseline and lowest intraoperative ScO2 values, but not relative ScO2 decrements,
were significantly associated with hospital mortality (p < 0.05), independent of
the EuroSCORE (p < 0.01). Receiver operating curve analysis of ScO2 values and
hospital mortality revealed an area under the curve (AUC) of 0.715 (p < 0.01) and
a cutoff value of <=50.5% for the baseline and ScO2, and an AUC of 0.718 (p <
0.05) and a cutoff value of <=35% for the lowest intraoperative ScO2. Low
baseline ScO2 (<=50%) was associated with increases in intubation time, intensive
care unit stay, hospital stay, and hospital mortality. CONCLUSION: Baseline ScO2
was reflective of severity of systemic comorbidities and was predictive of
clinical outcomes after major cardiovascular surgery. ScO2 correlated most
significantly with BNP in an exponential manner, suggesting that BNP plays a
major role in the ScO2-based outcome prediction.
PMID- 28704503
TI - Role of biomarkers in early infectious complications after lung transplantation.
AB - BACKGROUND: Infections and primary graft dysfunction are devastating
complications in the immediate postoperative period following lung
transplantation. Nowadays, reliable diagnostic tools are not available.
Biomarkers could improve early infection diagnosis. METHODS: Multicentre
prospective observational study that included all centres authorized to perform
lung transplantation in Spain. Lung infection and/or primary graft dysfunction
presentation during study period (first postoperative week) was determined.
Biomarkers were measured on ICU admission and daily till ICU discharge or for the
following 6 consecutive postoperative days. RESULTS: We included 233 patients.
Median PCT levels were significantly lower in patients with no infection than in
patients with Infection on all follow up days. PCT levels were similar for PGD
grades 1 and 2 and increased significantly in grade 3. CRP levels were similar in
all groups, and no significant differences were observed at any study time point.
In the absence of PGD grade 3, PCT levels above median (0.50 ng/ml on admission
or 1.17 ng/ml on day 1) were significantly associated with more than two- and
three-fold increase in the risk of infection (adjusted Odds Ratio 2.37, 95%
confidence interval 1.06 to 5.30 and 3.44, 95% confidence interval 1.52 to 7.78,
respectively). CONCLUSIONS: In the absence of severe primary graft dysfunction,
procalcitonin can be useful in detecting infections during the first
postoperative week. PGD grade 3 significantly increases PCT levels and interferes
with the capacity of PCT as a marker of infection. PCT was superior to CRP in the
diagnosis of infection during the study period.
PMID- 28704504
TI - Sanitation practices and perceptions in Kakuma refugee camp, Kenya: Comparing the
status quo with a novel service-based approach.
AB - Globally, an estimated 2.5 billion people lack access to improved sanitation.
Unimproved sanitation increases the risk of morbidity and mortality, especially
in protracted refugee situations where sanitation is based on pit latrine use.
Once the pit is full, waste remains in the pit, necessitating the construction of
a new latrine, straining available land and funding resources. A viable,
sustainable solution is needed. This study used qualitative and quantitative
methods to design, implement, and pilot a novel sanitation system in Kakuma
refugee camp, Kenya. An initial round of 12 pre-implementation focus group
discussions (FGDs) were conducted with Dinka and Somali residents to understand
sanitation practices, perceptions, and needs. FGDs and a supplementary pre
implementation survey informed the development of an innovative sanitation
management system that incorporated the provision of urine and liquid-diverting
toilets, which separate urine and fecal waste, and a service-based sanitation
system that included weekly waste collection. The new system was implemented on a
pilot scale for 6 weeks. During the implementation, bi-weekly surveys were
administered in each study household to monitor user perceptions and challenges.
At the end of the pilot, the sanitation system was assessed using a second round
of four post-implementation FGDs. Those who piloted the new sanitation system
reported high levels of user satisfaction. Reported benefits included odor
reduction, insect/pest reduction, the sitting design, the appropriateness for
special populations, and waste collection. However, urine and liquid diversion
presented a challenge for users who perform anal washing and for women who had
experienced female genital mutilation. Refugee populations are often culturally
and ethnically diverse. Using residents' input to inform the development of
sanitation solutions can increase user acceptability and provide opportunities to
improve sanitation system designs based on specific needs.
PMID- 28704505
TI - CSmiRTar: Condition-Specific microRNA targets database.
AB - MicroRNAs (miRNAs) are functional RNA molecules which play important roles in the
post-transcriptional regulation. miRNAs regulate their target genes by repressing
translation or inducing degradation of the target genes' mRNAs. Many databases
have been constructed to provide computationally predicted miRNA targets.
However, they cannot provide the miRNA targets expressed in a specific tissue and
related to a specific disease at the same time. Moreover, they cannot provide the
common targets of multiple miRNAs and the common miRNAs of multiple genes at the
same time. To solve these two problems, we construct a database called CSmiRTar
(Condition-Specific miRNA Targets). CSmiRTar collects computationally predicted
targets of 2588 human miRNAs and 1945 mouse miRNAs from four most widely used
miRNA target prediction databases (miRDB, TargetScan, microRNA.org and DIANA
microT) and implements functional filters which allows users to search (i) a
miRNA's targets expressed in a specific tissue or/and related to a specific
disease, (ii) multiple miRNAs' common targets expressed in a specific tissue
or/and related to a specific disease, (iii) a gene's miRNAs related to a specific
disease, and (iv) multiple genes' common miRNAs related to a specific disease. We
believe that CSmiRTar will be a useful database for biologists to study the
molecular mechanisms of post-transcriptional regulation in human or mouse.
CSmiRTar is available at http://cosbi.ee.ncku.edu.tw/CSmiRTar/ or
http://cosbi4.ee.ncku.edu.tw/CSmiRTar/.
PMID- 28704506
TI - Microfluidic assay of circulating endothelial cells in coronary artery disease
patients with angina pectoris.
AB - BACKGROUND: Circulating endothelial cells (CECs) are widely reported as a
promising biomarker of endothelial damage/dysfunction in coronary artery disease
(CAD). The two popular methods of CEC quantification include the use of
immunomagnetic beads separation (IB) and flow cytometry analysis (FC); however,
they suffer from two main shortcomings that affect their diagnostic and
prognostic responses: non-specific bindings of magnetic beads to non-target cells
and a high degree of variability in rare cell identification, respectively. We
designed a microfluidic chip with spatially staggered micropillars for the
efficient harvesting of CECs with intact cellular morphology in an attempt to
revisit the diagnostic goal of CEC counts in CAD patients with angina pectoris.
METHODS: A label-free microfluidic assay that involved an in-situ enumeration and
immunofluorescent identification (DAPI+/CD146+/VEGFR1+/CD45-) of CECs was carried
out to assess the CEC count in human peripheral blood samples. A total of 55 CAD
patients with angina pectoris [16 with chronic stable angina (CSA) and 39 with
unstable angina (UA)], together with 15 heathy controls (HCs) were enrolled in
the study. RESULTS: CEC counts are significantly higher in both CSA and UA groups
compared to the HC group [respective medians of 6.9, 10.0 and 1.5 cells/ml (p <
0.01)]. Further, a significant elevation of CEC count was observed in the three
UA subgroups [low risk (5.3) vs. intermediate risk (10.8) vs. high risk (18.0)
cells/ml, p < 0.001) classified in accordance to the TIMI NSTEMI/UA risk score
system. From the receiver-operating characteristic curve analysis, the AUCs for
distinguishing CSA and UA from HC were 0.867 and 0.938, respectively. The
corresponding sensitivities were 87.5% and 84.6% and the specificities were 66.7%
and 86.7%, respectively. CONCLUSIONS: Our microfluidic assay system is efficient
and stable for CEC capture and enumeration. The results showed that the CEC count
has the potential to be a promising clinical biomarker for the assessment of
endothelial damage/dysfunction in CAD patients with angina pectoris.
PMID- 28704507
TI - Regular moist snuff dipping does not affect endurance exercise performance.
AB - Physiological and medical effects of snuff have previously been obtained either
in cross-sectional studies or after snuff administration to non-tobacco users.
The effects of snuff cessation after several years of daily use are unknown. 24
participants with >2 years of daily snuff-use were tested before and after >6
weeks snuff cessation (SCG). A control group (CO) of 11 snuff users kept their
normal habits. Resting heart rate (HR) and blood pressure (BP) were significantly
lower in SCG after snuff cessation, and body mass was increased by 1.4 +/- 1.7
kg. Total cholesterol increased from 4.12 +/- 0.54 (95% CI 3.89-4.35) to 4.46 +/-
0.70 (95% CI 4.16-4.75) mM L-1 in SCG, due to increased LDL, and this change was
significantly different from CO. Resting values of HDL, C-reactive protein, and
free fatty acids (FFA) remained unchanged in both groups. In SCG group, both HR
and BP were reduced during a four-stage incremental cycling test (from 50 to 80%
of VO2max) and a prolonged cycling test (60 min at 50% of VO2max). Oxygen uptake
(VO2), respiratory exchange ratio, blood lactate (bLa) and blood glucose (bGlu)
concentration, and rate of perceived exertion (RPE) were unchanged. In CO group,
all measurements were unchanged. During the prolonged cycling test, FFA was
reduced, but with no significant difference between groups. During the maximal
treadmill running test peak values of VO2, pulmonary ventilation (VE), time to
exhaustion and bLa were unchanged in both groups. In conclusion, endurance
exercise performance (VO2max and maximal endurance time) does not seem to be
affected by prolonged snuff use, while effects on cardiovascular risk factors are
contradictory. HR and BP during rest and submaximal exercise are reduced after
cessation of regular use of snuff. Evidently, the long-time adrenergic stress on
circulation is reversible.
PMID- 28704508
TI - Lifestyle behaviours of Lebanese-Australians: Cross-sectional findings from The
45 and Up Study.
AB - Little is known regarding the health and lifestyle behaviours of Australians of
Lebanese ethnicity. The available evidence suggests that Australians of Lebanese
ethnicity who were born in Lebanon reportedly have higher rates of cardiovascular
disease-related and type 2 diabetes-related complications when compared with the
wider Australian population. The aim of this study is to compare lifestyle
behaviours of middle-aged to older adults of Lebanese ethnicity born in Lebanon,
Australia, and elsewhere to those of Australian ethnicity. Participants were
37,419 Australians aged >=45 years, from the baseline dataset of The 45 and Up
Study which included 4 groups of interest: those of Australian ethnicity (n =
36,707) [Reference]; those of Lebanese ethnicity born in Lebanon (n = 346); 302
those of Lebanese ethnicity born in Australia (n = 302); and those of Lebanese
ethnicity born elsewhere (n = 64). Multilevel logistic regression was used to
examine the odds of those of Lebanese ethnicity reporting suboptimal lifestyle
behaviours (insufficient physical activity, prolonged sitting, smoking, sleep
duration, and various diet-related behaviours) relative to those of Australian
ethnicity. Multilevel linear regression was used to examine the clustering of
suboptimal lifestyle behaviours through a 'lifestyle index' score ranging from 0
9 (sum of all lifestyle behaviours for each subject). The lifestyle index score
was lower among Lebanese-born (-0.36, 95% CI -0.51, -0.22, p<0.001) and
Australian-born (-0.17, 95% CI -0.32, -0.02, p = 0.031) people of Lebanese
ethnicity in comparison to those of Australian ethnicity. Those of Lebanese
ethnicity born in Lebanon had higher odds of reporting suboptimal lifestyle
behaviours for physical activity, smoking, and sleep duration, and lower odds of
reporting optimal lifestyle behaviours for sitting time, fruit, processed meat,
and alcohol consumption, when compared with those of Australian ethnicity.
Differences in the individual lifestyle behaviours for those of Lebanese
ethnicity born in Australia and elsewhere compared with those of Australian
ethnicity were fewer. Lifestyle behaviours of those of Lebanese ethnicity vary by
country of birth and a lower level of suboptimal lifestyle behaviour clustering
was apparent among Lebanese-born and Australian-born middle-aged to older adults
of Lebanese ethnicity.
PMID- 28704509
TI - Effects of hemoperfusion and continuous renal replacement therapy on patient
survival following paraquat poisoning.
AB - Mortality in patients with paraquat (PQ) poisoning is related to plasma PQ
levels. Concentrations lower than 5,000 ng/mL are considered critical but
curable. This study assessed the effects of hemoperfusion (HP) and continuous
renal replacement therapy (CRRT) on the survival of PQ-poisoned patients with
plasma PQ levels below 5,000ng/mL. We analyzed the records of 164 patients with
PQ poisoning who were treated at the First Affiliated Hospital of Wenzhou Medical
University in China between January 2011 and May 2015. We divided these patients
into six sub-groups based on baseline plasma PQ levels and treatment, compared
their clinical characteristics, and analyzed their survival rates. Patient sub
groups did not differ in terms of age, sex, time between poisoning and hospital
admission, or time to first gavage. Biochemical indicators improved over time in
all sub-groups following treatment, and the combined HP and CRRT treatment
yielded better results than HP or CRRT alone. Fatality rates in the three
treatment sub-groups did not differ among patients with baseline plasma PQ levels
of 50-1,000 ng/mL, but in patients with 1,000-5,000 ng/mL levels, the mortality
rate was 59.2% (HP treatment group), 48% (CRRT treatment group), and 37.9%
(combined treatment group). Mortality rates were higher 10-30 days after
hospitalization than in the first 10 days after admission. In the early stages of
PQ poisoning, CRRT is effective in reducing patient fatality rates, particularly
when combined with HP. Our data could be useful in increasing survival in acute
PQ poisoning patients.
PMID- 28704510
TI - Combining global land cover datasets to quantify agricultural expansion into
forests in Latin America: Limitations and challenges.
AB - While we know that deforestation in the tropics is increasingly driven by
commercial agriculture, most tropical countries still lack recent and spatially
explicit assessments of the relative importance of pasture and cropland expansion
in causing forest loss. Here we present a spatially explicit quantification of
the extent to which cultivated land and grassland expanded at the expense of
forests across Latin America in 2001-2011, by combining two "state-of-the-art"
global datasets (Global Forest Change forest loss and GlobeLand30-2010 land
cover). We further evaluate some of the limitations and challenges in doing this.
We find that this approach does capture some of the major patterns of land cover
following deforestation, with GlobeLand30-2010's Grassland class (which we
interpret as pasture) being the most common land cover replacing forests across
Latin America. However, our analysis also reveals some major limitations to
combining these land cover datasets for quantifying pasture and cropland
expansion into forest. First, a simple one-to-one translation between GlobeLand30
2010's Cultivated land and Grassland classes into cropland and pasture
respectively, should not be made without caution, as GlobeLand30-2010 defines its
Cultivated land to include some pastures. Comparisons with the TerraClass dataset
over the Brazilian Amazon and with previous literature indicates that Cultivated
land in GlobeLand30-2010 includes notable amounts of pasture and other vegetation
(e.g. in Paraguay and the Brazilian Amazon). This further suggests that the
approach taken here generally leads to an underestimation (of up to ~60%) of the
role of pasture in replacing forest. Second, a large share (~33%) of the Global
Forest Change forest loss is found to still be forest according to GlobeLand30
2010 and our analysis suggests that the accuracy of the combined datasets,
especially for areas with heterogeneous land cover and/or small-scale forest
loss, is still too poor for deriving accurate quantifications of land cover
following forest loss.
PMID- 28704511
TI - Genetic variation analysis and relationships among environmental strains of
Scedosporium apiospermum sensu stricto in Bangkok, Thailand.
AB - The Scedosporium apiospermum species complex is an emerging filamentous fungi
that has been isolated from environment. It can cause a wide range of infections
in both immunocompetent and immunocompromised individuals. We aimed to study the
genetic variation and relationships between 48 strains of S. apiospermum sensu
stricto isolated from soil in Bangkok, Thailand. For PCR, sequencing and
phylogenetic analysis, we used the following genes: actin; calmodulin exons 3 and
4; the second largest subunit of the RNA polymerase II; beta-tubulin exon 2-4;
manganese superoxide dismutase; internal transcribed spacer; transcription
elongation factor 1alpha; and beta-tubulin exons 5 and 6. The present study is
the first phylogenetic analysis of relationships among S. apiospermum sensu
stricto in Thailand and South-east Asia. This result provides useful information
for future epidemiological study and may be correlated to clinical manifestation.
PMID- 28704512
TI - A role for the Drosophila zinc transporter Zip88E in protecting against dietary
zinc toxicity.
AB - Zinc absorption in animals is thought to be regulated in a local, cell autonomous
manner with intestinal cells responding to dietary zinc content. The Drosophila
zinc transporter Zip88E shows strong sequence similarity to Zips 42C.1, 42C.2 and
89B as well as mammalian Zips 1, 2 and 3, suggesting that it may act in concert
with the apically-localised Drosophila zinc uptake transporters to facilitate
dietary zinc absorption by importing ions into the midgut enterocytes. However,
the functional characterisation of Zip88E presented here indicates that Zip88E
may instead play a role in detecting and responding to zinc toxicity. Larvae
homozygous for a null Zip88E allele are viable yet display heightened sensitivity
to elevated levels of dietary zinc. This decreased zinc tolerance is accompanied
by an overall decrease in Metallothionein B transcription throughout the larval
midgut. A Zip88E reporter gene is expressed only in the salivary glands, a
handful of enteroendocrine cells at the boundary between the anterior and middle
midgut regions, and in two parallel strips of sensory cell projections connecting
to the larval ventral ganglion. Zip88E expression solely in this restricted
subset of cells is sufficient to rescue the Zip88E mutant phenotype. Together,
our data suggest that Zip88E may be functioning in a small subset of cells to
detect excessive zinc levels and induce a systemic response to reduce dietary
zinc absorption and hence protect against toxicity.
PMID- 28704513
TI - Amplification of overlapping DNA amplicons in a single-tube multiplex PCR for
targeted next-generation sequencing of BRCA1 and BRCA2.
AB - Current PCR-based target enrichment methods for next generation sequencing (NGS)
of overlapping amplicons often requires separate PCR reactions and subsequent
pooling of amplicons from the different reactions. The study presents a novel
method, deemed stem-loop inhibition mediated amplification (SLIMamp), for
amplifying overlapping or tiled amplicons in a single multiplex PCR reaction.
During a SLIMamp PCR reaction, a stem loop structure formed by the overlapping
amplicon suppresses additional amplification of itself by preventing the
annealing of the primers. Using the SLIMamp strategy, we designed a next
generation sequencing (NGS) assay to enrich the exon regions of BRCA1 and BRCA2
for sequencing on an Illumina MiSeq system. We used 35 cell line DNAs and 6
patient blood DNAs in the study to evaluate the assay performance. For each
sample, all targeted regions were successfully amplified and sequenced with
excellent coverage uniformity and specificity. >99% of the total sequencing reads
were mapped to the human reference genome (hg19) and >99% of the mapped reads
were on the targeted exons. >98% of bases were covered at >0.20x of the mean
coverage and >99% are covered at >0.15x of the mean depth. Among 34 independently
sequenced samples, all variants were reliably detected with no false positives or
false negatives. SLIMamp provides a robust method for single-tube multiplex PCR
amplification of numerous, overlapping amplicons that tile for targeted next
generation sequencing.
PMID- 28704514
TI - Feedback activation of AMPK-mediated autophagy acceleration is a key resistance
mechanism against SCD1 inhibitor-induced cell growth inhibition.
AB - Elucidating the bioactive compound modes of action is crucial for increasing
success rates in drug development. For anticancer drugs, defining effective drug
combinations that overcome resistance improves therapeutic efficacy. Herein, by
using a biologically annotated compound library, we performed a large-scale
combination screening with Stearoyl-CoA desaturase-1 (SCD1) inhibitor, T-3764518,
which partially inhibits colorectal cancer cell proliferation. T-3764518 induced
phosphorylation and activation of AMPK in HCT-116 cells, which led to blockade of
downstream fatty acid synthesis and acceleration of autophagy. Attenuation of
fatty acid synthesis by small molecules suppressed the growth inhibitory effect
of T-3764518. In contrast, combination of T-3764518 with autophagy flux
inhibitors synergistically inhibited cellular proliferation. Experiments using
SCD1 knock-out cells validated the results obtained with T-3764518. The results
of our study indicated that activation of autophagy serves as a survival signal
when SCD1 is inhibited in HCT-116 cells. Furthermore, these findings suggest that
combining SCD1 inhibitor with autophagy inhibitors is a promising anticancer
therapy.
PMID- 28704515
TI - Structural characterization of chaos game fractals using small-angle scattering
analysis.
AB - Small-angle scattering (SAS) technique is applied to study the nano and
microstructural properties of spatial patterns generated from chaos game
representation (CGR). Using a simplified version of Debye formula, we calculate
and analyze in momentum space, the monodisperse scattering structure factor from
a system of randomly oriented and non-interacting 2D Sierpinski gaskets (SG). We
show that within CGR approach, the main geometrical and fractal properties, such
as the overall size, scaling factor, minimal distance between scattering units,
fractal dimension and the number of units composing the SG, can be recovered. We
confirm the numerical results, by developing a theoretical model which describes
analytically the structure factor of SG. We apply our findings to scattering from
single scale mass fractals, and respectively to a multiscale fractal representing
DNA sequences, and for which an analytic description of the structure factor is
not known a priori.
PMID- 28704516
TI - Ultrasound diagnosis of transverse sinus hypoplasia using flow profiles of the
internal jugular vein.
AB - Accurate diagnosis of subtypes of transverse sinus (TS) hypoplasia requires more
expensive methods like magnetic resonance (MR) imaging. We hypothesized
ultrasound findings of the internal jugular vein (IJV) can be surrogate
indicators for diagnosis of TS hypoplasia. MR images were reviewed in 131
subjects to evaluate TS diameter and the location and degree of venous flow
stenosis and obstruction. Ultrasound parameters including the cross-sectional
lumen area (CSA), time-average-mean velocity (TAMV), and flow volume (FV) at each
IJV segment were also evaluated. Sixty-nine subjects had TS hypoplasia based on
MRV criteria, of which 39 TS hypoplasia were considered a subtype of TS
hypoplasia, which is secondary to the downstream venous compression/stenosis or
left brachiocephalic vein. In the ultrasound study, the CSA of the IJV
ipsilateral to TS hypoplasia was significantly smaller. Further, a
contralateral/ipsilateral IJV CSA ratio >1.55 provided good sensitivity,
specificity, and positive predictive value for discriminating TS hypoplasia.
PMID- 28704517
TI - Zinc oxide nanoparticles as a substitute for zinc oxide or colistin sulfate:
Effects on growth, serum enzymes, zinc deposition, intestinal morphology and
epithelial barrier in weaned piglets.
AB - The objective of this study was to evaluate effects of zinc oxide nanoparticles
(nano-ZnOs) as a substitute for colistin sulfate (CS) and/or zinc oxide (ZnO) on
growth performance, serum enzymes, zinc deposition, intestinal morphology and
epithelial barrier in weaned piglets. A total of 216 crossbred
Duroc*(Landrace*Yorkshire) piglets weaned at 23 days were randomly assigned into
3 groups, which were fed with basal diets supplemented with 20 mg/kg CS (CS
group), 20mg/kg CS+3000 mg/kg ZnO (CS+ZnO group), and 1200 mg/kg nano-ZnOs (nano
ZnO group) for 14 days. Results indicated that compared to CS group,
supplementation of 1200 mg/kg nano-ZnOs (about 30 nm) significantly increased
final body weight and average daily gain, and 3000 mg/kg ZnO plus colistin
sulfate significantly increased average daily gain and decreased diarrhea rate in
weaned piglets. There was no significant difference in growth performance and
diarrhea rate between nano-ZnO and CS+ZnO groups. Supplementation of nano-ZnOs
did not affect serum enzymes (glutamic oxalacetic transaminase, glutamic-pyruvic
transaminase, and lactate dehydrogenase), but significantly increased plasma and
tissue zinc concentrations (liver, tibia), improved intestinal morphology
(increased duodenal and ileal villus length, crypt depth, and villus surface),
enhanced mRNA expression of ZO-1 in ileal mucosa, and significantly decreased
diamine oxidase activity in plasma, total aerobic bacterial population in MLN as
compared to CS group. Effects of nano-ZnOs on serum enzymes, intestinal
morphology, and mRNA expressions of tight junction were similar to those of high
dietary ZnO plus colistin sulfate, while nano-ZnOs significantly reduced zinc
concentrations of liver, tibia, and feces, and decreased total aerobic bacterial
population in MLN as compared to CS+ZnO group. These results suggested that nano
ZnOs (1200 mg/kg) might be used as a substitute for colistin sulfate and high
dietary ZnO in weaned piglets.
PMID- 28704518
TI - Photosynthetic, morphological, and reproductive variations in Cypripedium
tibeticum in relation to different light regimes in a subalpine forest.
AB - Cypripedium tibeticum, a subalpine orchid species, inhabits various habitats of
subalpine forests, mainly including the forest edge (FE), forest gap (FG), and
understory (UST), which have significantly different light intensities (FE > FG >
UST). However, the ecological and physiological influences caused by different
light regimes in this species are still poorly understood. In the present study,
photosynthetic, morphological, and reproductive characteristics were
comprehensively studied in plants of C. tibeticum grown in three types of
habitats. The photosynthetic capacities, such as the net photosynthetic rate,
light-saturated photosynthesis (Pmax), and dry mass per unit leaf area (LMA),
were higher in FE and FG than in UST according to light availability. Compared
with FG, the populations in FE and UST suffer from excessively strong and
inadequate radiation, respectively, which was further corroborated by the low
Fv/Fm in FE and high apparent quantum yield (AQY) in FG. The leaves of the
orchids had various proportions of constituents, such as the leaf area, thickness
and (or) epidermal hair, to reduce damage from high radiation (including
ultraviolet-b radiation) in FE and capture more light in FG and UST. Although the
flower rate (FR) was positively correlated to both Pmax and the daily mean PAR,
fruit-set only occurred in the populations in FG. The failures in FE and UST
might be ascribed to changes in the floral functional structure and low biomass
accumulation, respectively. Moreover, analysis of the demographic statistics
showed that FG was an advantageous habitat for the orchid. Thus, C. tibeticum
reacted to photosynthetic and morphological changes to adapt to different
subalpine forest habitats, and neither full (under FE) nor low (UST) illumination
was favorable for population expansion. These findings could serve as a guide for
the protection and reintroduction of C. tibeticum and emphasize the importance of
specific habitats for Cypripedium spp.
PMID- 28704519
TI - E2F1 somatic mutation within miRNA target site impairs gene regulation in
colorectal cancer.
AB - BACKGROUND: Genetic studies have largely concentrated on the impact of somatic
mutations found in coding regions, and have neglected mutations outside of these.
However, 3' untranslated regions (3' UTR) mutations can also disrupt or create
miRNA target sites, and trigger oncogene activation or tumor suppressor
inactivation. METHODS: We used next-generation sequencing to widely screen for
genetic alterations within predicted miRNA target sites of oncogenes associated
with colorectal cancer, and evaluated the functional impact of a new somatic
mutation. Target sequencing of 47 genes was performed for 29 primary colorectal
tumor samples. For 71 independent samples, Sanger methodology was used to screen
for E2F1 mutations in miRNA predicted target sites, and the functional impact of
these mutations was evaluated by luciferase reporter assays. RESULTS: We
identified germline and somatic alterations in E2F1. Of the 100 samples
evaluated, 3 had germline alterations at the MIR205-5p target site, while one had
a somatic mutation at MIR136-5p target site. E2F1 gene expression was similar
between normal and tumor tissues bearing the germline alteration; however,
expression was increased 4-fold in tumor tissue that harbored a somatic mutation
compared to that in normal tissue. Luciferase reporter assays revealed both
germline and somatic alterations increased E2F1 activity relative to wild-type
E2F1. CONCLUSIONS: We demonstrated that somatic mutation within E2F1:MIR136-5p
target site impairs miRNA-mediated regulation and leads to increased gene
activity. We conclude that somatic mutations that disrupt miRNA target sites have
the potential to impact gene regulation, highlighting an important mechanism of
oncogene activation.
PMID- 28704520
TI - A self-affirmation exercise does not improve intentions to vaccinate among
parents with negative vaccine attitudes (and may decrease intentions to
vaccinate).
AB - Two studies investigated the effectiveness of a self-affirmation exercise on
vaccine safety beliefs and intent to vaccinate future children. In Study 1, a
sample of 585 parents with at least one child under the age of 18 in the home
participated through Amazon's MTurk. Participants were randomly assigned to one
of four conditions in a 2 x 2 design. Participants read either correcting
information refuting a link between the measles, mumps, and rubella (MMR) vaccine
and autism or a control passage about bird feeding. Additionally, participants
either completed a self-affirmation exercise where they reflected on their
personal values or in a control condition in which they reflected on least
personally-important values that might be important to others. Participants
exposed to the correcting information were less likely to believe that vaccines
cause serious side effects, but no less likely to believe that the MMR vaccine
causes autism. For parents with initially positive vaccine attitudes, there was
no effect of condition on intent to vaccinate a future child. For parents with
initially negative vaccine attitudes, self-affirmation was ineffective in the
presence of correcting information and resulted in less intention to vaccinate in
the absence of correcting information. This effect was partially replicated in
Study 2 (N = 576), which provided no correcting information but otherwise
followed the same procedure as Study 1.
PMID- 28704521
TI - Prognostic value of circulating plasma cells in patients with multiple myeloma: A
meta-analysis.
AB - PURPOSE: The clinical significance and prognostic role of circulating plasma
cells (CPCs) in multiple myeloma (MM) are still controversial. We conducted the
first meta-analysis to clarify the correlation between CPCs and the
clinicopathological features and prognosis of MM patients. METHODS: A
comprehensive literary search for relevant studies was performed on PubMed,
Embase, Medline, CNKI (Chinese) and Web of Science databases (January 1, 1950 to
December 20, 2016). The associations between CPCs and survival rate and
clinicopathological parameters, including International staging system (ISS) and
Durie-Salm staging system (DS) stage, were evaluated. Then pooled hazard ratios
(HRs) for survival with 95% confidence intervals (CIs), subgroup analysis,
sensitivity analysis, and publication bias were conducted. RESULTS: 11 studies
covering a total of 2943 patients were included. Pooled hazard ratios (HRs)
revealed that the presence of CPCs predicted aggressive disease progression (HR =
1.78, 95% CI = 1.57-2.03) and reduced overall survival (OS) (HR = 1.82, 95% CI =
1.59-2.08). Subgroup analyses demonstrated that CPCs positive patients also had
poor disease progression and OS in detection methods and sampling time subsets.
Moreover, the presence of CPCs was strikingly associated with increased ISS stage
(OR = 2.78% CI = 1.69-4.56), but not with DS stage(OR = 1.60; 95% CI = 0.74
3.47). CONCLUSIONS: CPCs status is associated with poorer survival outcome in
multiple myeloma. Additionally, increased ISS stage could be significant risk
factors for the presence of CPCs.
PMID- 28704522
TI - Assessment of gut microbiota populations in lean and obese Zucker rats.
AB - Obesity has been on the rise in the US and worldwide for the last several
decades. Obesity has been associated with chronic disease development, such as
certain types of cancer, type 2 diabetes, cardiovascular disease, and liver
diseases. Previously, we reported that obesity promotes DMBA-induced mammary
tumor development using the obese Zucker rat model. The intestinal microbiota is
composed of a diverse population of obligate and facultative anaerobic
microorganisms, and these organisms carry out a broad range of metabolic
activities. Obesity has been linked to changes in the intestinal microbiota, but
the composition of the bacterial populations in lean and obese Zucker rats has
not been carefully studied. Therefore, the objective of this study was to
determine the effects of obesity on the gut microbiota in this model. Lean and
obese female Zucker rats (n = 16) were fed an AIN-93G-like diet for 8 weeks. Rats
were weighed twice weekly, and fecal samples were collected at the beginning and
end of the experiment. 16S rRNA gene sequencing was used to evaluate the
composition of the fecal bacterial populations. At the outset of the study, the
lean rats exhibited much lower ratios of the Firmicutes to Bacteroidetes phyla
than the obese rats, but after 60 days, this ratio in the lean rats exceeded that
of the obese. This shift was associated with reductions in the Bacteroidaceae,
S24-7 and Paraprevotellaceae families in the lean rats. Obese rats also showed
increased levels of the genus Akkermansia at day 60. PCoA plots of beta diversity
showed clustering of the different test groups, indicating clear differences in
intestinal microbiota populations associated with both the time point of the
study and the lean or obese status in the Zucker rat model for obesity.
PMID- 28704523
TI - Leg length change after opening wedge and closing wedge high tibial osteotomy: A
meta-analysis.
AB - BACKGROUND: Theoretical considerations suggest that leg length increases after
opening wedge high tibial osteotomy (HTO) and decreases after closing wedge HTO;
however, in vivo studies have yielded conflicting results. This meta-analysis
therefore assessed changes in leg length after opening wedge and closing wedge
HTO. METHODS: All studies comparing pre- and postoperative leg length in patients
who underwent opening and/or closing wedge HTO were included. Two reviewers
independently recorded data from each study in terms of sample size as well as
preoperative and postoperative leg length of open wedge and/or closed wedge HTO
groups. RESULTS: Four studies were included in the meta-analysis. Although pooled
results showed leg length changes from before to after surgery were -6.93 mm (95%
confidence interval [CI]: -17.53 to 3.67 mm; P = 0.20) in opening wedge HTO and
1.97 mm (95% CI: -7.13 to 11.07 mm; P = 0.67) in closing wedge HTO, respectively,
these values were statistically not significant. However, the difference in the
pooled mean leg length change from before to after surgery between opening wedge
and closing wedge HTO was 8 mm, a difference that was significant (95% CI: 6.53
to 9.46 mm; P<0.001). CONCLUSION: The change in leg length was not statistically
significant for either opening or closing wedge HTO. However, leg length change
from before to after surgery was 8 mm greater for opening wedge HTO than for
closing wedge HTO.
PMID- 28704524
TI - Prevalence of enteroviruses in healthy populations and excretion of pathogens in
patients with hand, foot, and mouth disease in a highly endemic area of southwest
China.
AB - Etiological carriers and the excretion of the pathogens causing hand, foot, and
mouth disease (HFMD) in healthy persons, patients, and asymptomatic persons
infected with HFMD as ongoing infection sources may play an important role in
perpetuating and spreading epidemics of HFMD. The aims of this study were to
determine the carrier status of EV-A71 and CV-A16 in healthy populations, as well
as the duration of EV-A71 and CV-A16 shedding in the stools of HFMD patients in
an epidemic area of southwest China. A cross-sectional study and a follow-up
study were conducted in three HFMD endemic counties of Yunnan Province. Six
hundred sixty-seven healthy subjects were recruited to participate in the cross
sectional study, and two stool specimens were collected from each subject. Among
the healthy subjects, 90 (13.5%) tested positive for viral isolation, but neither
EV-A71 nor CV-A16 was detected in healthy individuals. Of the 150 patients with
probable HFMD, 55.3% (83/150) tested positive for viral isolation with presented
serotypes such as EV-A71 (51.81%, 43/83), CV-A16 (32.53%, 27/83), other EVs
(13.25%, 11/83), and mixed EV-A71 and CV-A16 (2.41%, 2/83). The longest duration
of EV-A71 and CV-A16 shedding in stool specimens from patients with HFMD was >46
days after onset. The positive rate of EV-A71 in the stool specimens of confirmed
patients dropped to 50% by the end of the third week, and the same occurred with
CV-A16 by the end of approximately the seventh week after onset. Although
carriers of major causative agents of HFMD in healthy populations are fewer in
number, the prolonged shedding of pathogens in patients with HFMD may serve as an
important factor in perpetuating and spreading HFMD epidemics.
PMID- 28704525
TI - Rapid identification of genes controlling virulence and immunity in malaria
parasites.
AB - Identifying the genetic determinants of phenotypes that impact disease severity
is of fundamental importance for the design of new interventions against malaria.
Here we present a rapid genome-wide approach capable of identifying multiple
genetic drivers of medically relevant phenotypes within malaria parasites via a
single experiment at single gene or allele resolution. In a proof of principle
study, we found that a previously undescribed single nucleotide polymorphism in
the binding domain of the erythrocyte binding like protein (EBL) conferred a
dramatic change in red blood cell invasion in mutant rodent malaria parasites
Plasmodium yoelii. In the same experiment, we implicated merozoite surface
protein 1 (MSP1) and other polymorphic proteins, as the major targets of strain
specific immunity. Using allelic replacement, we provide functional validation of
the substitution in the EBL gene controlling the growth rate in the blood stages
of the parasites.
PMID- 28704526
TI - Chi-miR-4110 promotes granulosa cell apoptosis by targeting Sma- and Mad-related
protein 2 (Smad2) in the caprine ovary.
AB - Follicular atresia mainly results from the apoptosis of granulosa cells (GCs).
Whilst our previous investigations examined the role of chi-miR-4110 in
regulating ovarian function, the present study detected the role of chi-miR-4110
in GC development. We transfected caprine GCs cultured in vitro with chi-miR-4110
mimics. Results revealed that chi-miR-4110 decreased mRNA and protein levels of
Smad2 by targeting its 3'-untranslated region (3'UTR). FoxC1 and Sp1 mRNA and
protein levels markedly increased, whereas those of bHLHe22 significantly
decreased (P<0.01 or 0.05) in GCs transfected with the chi-miR-4110 mimics.
Further studies revealed a significantly higher number of apoptotic cells in GCs
transfected with the chi-miR-4110 mimics (P< 0.05) than in GCs transfected with
mimics negative control. GCs transfected with the chi-miR-4110 mimics exhibited
significantly increased mRNA and protein levels of the pro-apoptotic gene Bax
(P<0.01) and significantly decreased expression levels of the anti-apoptotic gene
BCL-2 (P<0.01). Smad2 interference (Si-1282) results were consistent with those
of the chi-miR-4110 mimics. Previous reports and our results showed that chi-miR
4110 increases Sp1 expression by repressing Smad2. The increase in Sp1 induces
p53-upregulated modulator of apoptosis, which increases the relative abundance of
Bax and causes caprine GC apoptosis. Our findings may provide relevant data for
the investigation of miRNA-mediated regulation of ovarian functions.
PMID- 28704527
TI - Correction: Effects of local and regional climatic fluctuations on dengue
outbreaks in southern Taiwan.
AB - [This corrects the article DOI: 10.1371/journal.pone.0178698.].
PMID- 28704528
TI - Retraction: Association between Polymorphism of the Interleukin-13 Gene and
Susceptibility to Hepatocellular Carcinoma in the Chinese Population.
PMID- 28704529
TI - Correction: Rediscovery of the enigmatic fungus-farming ant "Mycetosoritis" asper
Mayr (Hymenoptera: Formicidae): Implications for taxonomy, phylogeny, and the
evolution of agriculture in ants.
AB - [This corrects the article DOI: 10.1371/journal.pone.0176498.].
PMID- 28704530
TI - A complex association between DNA methylation and gene expression in human
placenta at first and third trimesters.
AB - The human placenta is a maternal-fetal organ essential for normal fetal
development and maternal health. During pregnancy, the placenta undergoes many
structural and functional changes in response to fetal needs and environmental
exposures. Previous studies have demonstrated widespread epigenetic and gene
expression changes from early to late pregnancy. However, on the global level,
how DNA methylation changes impact on gene expression in human placenta is not
yet well understood. We performed DNA methylome analysis by reduced
representation bisulfite sequencing (RRBS) and gene expression analysis by RNA
Seq for both first and third trimester human placenta tissues. From first to
third trimester, 199 promoters (corresponding to 189 genes) and 2,297 gene bodies
were differentially methylated, with a clear dominance of hypermethylation (96.8%
and 93.0% for promoters and gene bodies, respectively). A total of 2,447 genes
were differentially expressed, of which 77.2% were down-regulated. Gene ontology
analysis using differentially expressed genes were enriched for cell cycle and
immune response functions. The correlation between DNA methylation and gene
expression was non-linear and complex, depending on the genomic context (promoter
or gene body) and gene expression levels. A wide range of DNA methylation and
gene expression changes were observed at different gestational ages. The non
linear association between DNA methylation and gene expression indicates that
epigenetic regulation of placenta development is more complex than previously
envisioned.
PMID- 28704531
TI - Correction: Long-term trends in the honeybee 'whooping signal' revealed by
automated detection.
AB - [This corrects the article DOI: 10.1371/journal.pone.0171162.].
PMID- 28704532
TI - Correction: Functional analysis of the GmESR1 gene associated with soybean
regeneration.
AB - [This corrects the article DOI: 10.1371/journal.pone.0175656.].
PMID- 28704533
TI - Peripheral blood mitochondrial DNA content in relation to circulating metabolites
and inflammatory markers: A population study.
AB - Mitochondrial DNA (mtDNA) content might undergo significant changes caused by
metabolic derangements, oxidative stress and inflammation that lead to
development and progression of cardiovascular diseases. We, therefore,
investigated in a general population the association of peripheral blood mtDNA
content with circulating metabolites and inflammatory markers. We examined 310
subjects (50.6% women; mean age, 53.3 years) randomly selected from a Flemish
population. Relative mtDNA content was measured by quantitative real-time PCR in
peripheral blood cells. Peak circulating metabolites were quantified using
nuclear magnetic resonance spectroscopy. The level of inflammation was assessed
via established inflammatory markers. Using Partial Least Squares analysis, we
constructed 3 latent factors from the 44 measured metabolites that explained
62.5% and 8.5% of the variance in the contributing metabolites and the mtDNA
content, respectively. With adjustments applied, mtDNA content was positively
associated with the first latent factor (P = 0.002). We identified 6 metabolites
with a major impact on the construction of this latent factor including HDL3
apolipoproteins, tyrosine, fatty acid with alphaCH2, creatinine, beta-glucose and
valine. We summarized them into a single composite metabolite score. We observed
a negative association between the composite metabolic score and mtDNA content (P
= 0.001). We also found that mtDNA content was inversely associated with
inflammatory markers including hs-CRP, hs-IL6, white blood cell and neutrophil
counts as well as neutrophil-to-lymphocyte ratio (P<=0.0024). We demonstrated
that in a general population relative peripheral blood mtDNA content was
associated with circulating metabolites indicative of perturbed lipid metabolism
and with inflammatory biomarkers.
PMID- 28704534
TI - Short term variation in NTproBNP after lifestyle intervention in severe obesity.
AB - AIM: Natriuretic peptides are not only involved in cardiovascular adaption to
various conditions, but also in metabolic diseases. We performed this study to
assess the effect of a very short time of lifestyle inpatient intervention on
NTproBNP values in normotensive subjects with severe obesity and normal cardiac
function. METHODS: We recruited 14 consecutive obese normotensive subjects with
normal cardiac function who were aged 30 years and more and were referred to
inpatient rehabilitation in an academic clinic over a two months period. They
were examined at baseline and after a 3-weeks program including dietary
intervention with hypocaloric diet and assisted personalized physical aerobic and
anaerobic activities and compared to age, sex and BMI-matched control subjects
under usual care. RESULTS: BMI significantly decreased (40.8 +/-1.6 vs 42.3 +/-
1.6 kg/m2, p <0.0001). Median reduction in body weight was 4.9 kg (interquartile
range 2.4-5.2 kg). After diet and exercise-induced weight loss, plasma NTproBNP
levels showed an almost two-fold increase, which was statistically significant
(28.2 +/- 12.3 vs 17.2 +/- 13.2 ng/L, p = 0.01), and particularly relevant in the
subgroup with NT-proBNP values below median values compared to those with higher
values (p = 0.02). No significant variations were found in control subjects (18.0
+/- 13.0 vs 16.5 +/- 11.2 ng/L, p = 0.18). The lipid profile was significantly
ameliorated, and both HbA1c and insulin levels showed a marginally non
significant decrease after treatment. CONCLUSIONS: An almost two-fold increase in
NTproBNP levels was evident after a very short time period of lifestyle
intervention in normotensive severe obese patients without cardiac disease. This
finding might have clinical relevance, considering the role of NT-proBNP as risk
factor of impaired glucose tolerance.
PMID- 28704535
TI - Interferon-related genetic markers of necroinflammatory activity in chronic
hepatitis C.
AB - INTRODUCTION: Chronic hepatitis C (CHC) is a major cause of liver disease
worldwide which often leads to progressive liver inflammation, fibrosis,
cirrhosis and hepatocellular carcinoma (HCC). CHC displays heterogeneous
progression depending on a broad set of factors, some of them intrinsic to each
individual such as the patient's genetic profile. This study aims to evaluate the
contribution of certain genetic variants of crucial interferon alpha and lambda
signaling pathways to the hepatic necroinflammatory activity (NIA) grade of CHC
patients. METHODS: NIA was evaluated in 119 CHC patients by METAVIR scale and
classified as low (NIA = 0-2, n = 80) or high grade (NIA = 3, n = 39). In a
candidate gene approach, 64 SNPs located in 30 different genes related to
interferon pathways (IL-28B, IFNAR1-2, JAK-STAT and OAS1-3, among others) were
genotyped using the Illumina GoldenGate(r) Genotyping Assay. Statistical
association was determined by logistic regression and expressed as OR and 95% CI.
Those SNPs significantly associated were further adjusted by other covariates.
RESULTS: Seven SNPs located in IL-28B (rs12979860), JAK1 (rs11576173 and
rs1497056), TYK2 (rs280519), OAS1 (rs2057778), SOCS1 (rs33932899) and RNASEL
(rs3738579) genes were significantly related to severe NIA grade (p<0.05).
Regarding to clinical variables, elevated NIA was notably associated with
aspartate aminotransferase (AST) serum levels >40 IU/L (p<0.05) but not with
other clinical factors. Multivariate logistic regression analysis of these
factors reflected that AST (>40 IU/L), TYK2 rs280519 (G allele) and RNASEL
rs3738579 (G allele) were factors independently associated with elevated NIA
(p<0.05). AST concentration showed a moderate AUC value (AUC = 0.63), similar to
TYK2 (rs280519) and RNASEL (rs3738579) SNPs (AUC = 0.61, both) in the ROC_AUC
analysis. Interestingly, the model including all significant variables reached a
considerable predictive value (AUC = 0.74). CONCLUSION: The identified genetic
variants in interferon signaling pathways may constitute useful prognostic
markers of CHC progression. Further validation in larger cohorts of patients is
needed.
PMID- 28704536
TI - Phylogeography in Nassarius mud snails: Complex patterns in congeneric species.
AB - One major goal for phylogeographical studies is to elucidate respective roles of
multiple evolutionary and ecological forces that shape the current distribution
patterns. In marine and coastal ecosystems, it has been generated a common
realization that species with enormous population size and pelagic larval stages
can disperse across broad geographical scales, leading to weak or even no
phylogeographical structure across large geographical scales. However, the
violation of such realization has been frequently reported, and it remains
largely unexplored on mechanisms responsible for various phylogeographical
patterns observed in different species at varied geographical scales. Here, we
used a species-rich genus Nassarius to assess and compare phylogeographical
patterns in congeneric species, and discuss causes and consequences underlying
varied phylogeographical patterns. Interestingly, we observed complex
phylogeographical patterns both within single species and across multiple
species, and multiple analyses showed varied levels of genetic heterogeneity
among sites within and across species. Available evidence suggests that related
species with similar biological characteristics may not be necessary to result in
consistent phylogeographical patterns. Multiple factors, including larval
ecology, interactions between dispersal and natural selection, and human activity
mediated dispersal, can partially explain the complex patterns observed in this
study. Deep investigations should be performed on these factors, particularly
their respective roles in determining evolutionary/ecological processes to form
phylogeographical patterns in species with high dispersal capacities in marine
and coastal ecosystems.
PMID- 28704537
TI - Non-invasive localization of atrial ectopic beats by using simulated body surface
P-wave integral maps.
AB - Non-invasive localization of continuous atrial ectopic beats remains a
cornerstone for the treatment of atrial arrhythmias. The lack of accurate tools
to guide electrophysiologists leads to an increase in the recurrence rate of
ablation procedures. Existing approaches are based on the analysis of the P-waves
main characteristics and the forward body surface potential maps (BSPMs) or on
the inverse estimation of the electric activity of the heart from those BSPMs.
These methods have not provided an efficient and systematic tool to localize
ectopic triggers. In this work, we propose the use of machine learning techniques
to spatially cluster and classify ectopic atrial foci into clearly differentiated
atrial regions by using the body surface P-wave integral map (BSPiM) as a
biomarker. Our simulated results show that ectopic foci with similar BSPiM
naturally cluster into differentiated non-intersected atrial regions and that new
patterns could be correctly classified with an accuracy of 97% when considering 2
clusters and 96% for 4 clusters. Our results also suggest that an increase in the
number of clusters is feasible at the cost of decreasing accuracy.
PMID- 28704538
TI - Intestinal calcium and bile salts facilitate germination of Clostridium difficile
spores.
AB - Clostridium difficile (C. difficile) is an anaerobic gram-positive pathogen that
is the leading cause of nosocomial bacterial infection globally. C. difficile
infection (CDI) typically occurs after ingestion of infectious spores by a
patient that has been treated with broad-spectrum antibiotics. While CDI is a
toxin-mediated disease, transmission and pathogenesis are dependent on the
ability to produce viable spores. These spores must become metabolically active
(germinate) in order to cause disease. C. difficile spore germination occurs when
spores encounter bile salts and other co-germinants within the small intestine,
however, the germination signaling cascade is unclear. Here we describe a
signaling role for Ca2+ during C. difficile spore germination and provide direct
evidence that intestinal Ca2+ coordinates with bile salts to stimulate
germination. Endogenous Ca2+ (released from within the spore) and a putative AAA+
ATPase, encoded by Cd630_32980, are both essential for taurocholate-glycine
induced germination in the absence of exogenous Ca2+. However, environmental Ca2+
replaces glycine as a co-germinant and circumvents the need for endogenous Ca2+
fluxes. Cd630_32980 is dispensable for colonization in a murine model of C.
difficile infection and ex vivo germination in mouse ileal contents. Calcium
depletion of the ileal contents prevented mutant spore germination and reduced WT
spore germination by 90%, indicating that Ca2+ present within the
gastrointestinal tract plays a critical role in C. difficile germination,
colonization, and pathogenesis. These data provide a biological mechanism that
may explain why individuals with inefficient intestinal calcium absorption (e.g.,
vitamin D deficiency, proton pump inhibitor use) are more prone to CDI and
suggest that modulating free intestinal calcium is a potential strategy to curb
the incidence of CDI.
PMID- 28704539
TI - Streptococcus gallolyticus subsp. gallolyticus promotes colorectal tumor
development.
AB - Streptococcus gallolyticus subsp. gallolyticus (Sg) has long been known to have a
strong association with colorectal cancer (CRC). This knowledge has important
clinical implications, and yet little is known about the role of Sg in the
development of CRC. Here we demonstrate that Sg promotes human colon cancer cell
proliferation in a manner that depends on cell context, bacterial growth phase
and direct contact between bacteria and colon cancer cells. In addition, we
observed increased level of beta-catenin, c-Myc and PCNA in colon cancer cells
following incubation with Sg. Knockdown or inhibition of beta-catenin abolished
the effect of Sg. Furthermore, mice administered with Sg had significantly more
tumors, higher tumor burden and dysplasia grade, and increased cell proliferation
and beta-catenin staining in colonic crypts compared to mice receiving control
bacteria. Finally, we showed that Sg is present in the majority of CRC patients
and is preferentially associated with tumor compared to normal tissues obtained
from CRC patients. These results taken together establish for the first time a
tumor-promoting role of Sg that involves specific bacterial and host factors and
have important clinical implications.
PMID- 28704540
TI - Meta-analyses of the association of G6PC2 allele variants with elevated fasting
glucose and type 2 diabetes.
AB - OBJECTIVE: To collectively evaluate the association of glucose-6-phosphatase
catalytic unit 2 (G6PC2) allele variants with elevated fasting glucose (FG) and
type 2 diabetes (T2D). DESIGN: Meta-analysis. DATA SOURCES: PubMed, Web of
Knowledge and Embase databases. STUDY SELECTION: Full text articles of studies
that identified an association of G6PC2 with T2D and elevated FG. PATIENT
INVOLVEMENT: There was no T2D patient involvement in the analyses on the
association of FG with G6PC2, there were T2D patients and non-diabetes patient
involvement in the analyses on the association of T2D with G6PC2. STATISTICAL
ANALYSIS: Random-effects meta-analyses were used to calculate the pool effect
sizes. I2 metric and H2 tests were used to calculate the heterogeneity. Begg's
funnel plot and Egger's linear regression test were done to assess publication
bias. RESULTS: Of the 423 studies identified, 21 were eligible and included. Data
on three loci (rs560887, rs16856187 and rs573225) were available. The G allele at
rs560887 in three ethnicities, the C allele at rs16856187 and the A allele at
rs573225 all had a positive association with elevated FG. Per increment of G
allele at rs560887 and A allele at rs573225 resulted in a FG 0.070 mmol/l and
0.075 mmol/l higher (beta (95% CI) = 0.070 (0.060, 0.079), p = 4.635e-50 and
0.075 (0.065, 0.085), p = 5.856e-48, respectively). With regard to the
relationship of rs16856187 and FG, an increase of 0.152 (95% CI: 0.034-0.270; p =
0.011) and 0.317 (95% CI: 0.193-0.442, p = 6.046e-07) was found in the
standardized mean difference (SMD) of FG for the AC and CC genotypes,
respectively, when compared with the AA reference genotype. However, the G-allele
of rs560887 in Caucasians under the additive model and the C-allele of rs16856187
under the allele and dominant models were associated with a decreased risk of T2D
(OR (95% CI) = 0.964 (0.947, 0.981), p = 0.570e-4; OR (95% CI) = 0.892 (0.832,
0.956), p = 0.001; and OR (95% CI) = 0.923(0.892, 0.955), p = 5.301e-6,
respectively). CONCLUSIONS: Our meta-analyses demonstrate that all three allele
variants of G6PC2 (rs560887, rs16856187 and rs573225) are associated with
elevated FG, with two variants (rs560887 in the Caucasians subgroup and
rs16856187 under the allele and dominant model) being associated with T2D as
well. Further studies utilizing larger sample sizes and different ethnic
populations are needed to extend and confirm these findings.
PMID- 28704541
TI - Increased genetic diversity and prevalence of co-infection with Trypanosoma spp.
in koalas (Phascolarctos cinereus) and their ticks identified using next
generation sequencing (NGS).
AB - Infections with Trypanosoma spp. have been associated with poor health and
decreased survival of koalas (Phascolarctos cinereus), particularly in the
presence of concurrent pathogens such as Chlamydia and koala retrovirus. The
present study describes the application of a next-generation sequencing (NGS)
based assay to characterise the prevalence and genetic diversity of trypanosome
communities in koalas and two native species of ticks (Ixodes holocyclus and I.
tasmani) removed from koala hosts. Among 168 koalas tested, 32.2% (95% CI: 25.2
39.8%) were positive for at least one Trypanosoma sp. Previously described
Trypanosoma spp. from koalas were identified, including T. irwini (32.1%, 95% CI:
25.2-39.8%), T. gilletti (25%, 95% CI: 18.7-32.3%), T. copemani (27.4%, 95% CI:
20.8-34.8%) and T. vegrandis (10.1%, 95% CI: 6.0-15.7%). Trypanosoma noyesi was
detected for the first time in koalas, although at a low prevalence (0.6% 95% CI:
0-3.3%), and a novel species (Trypanosoma sp. AB-2017) was identified at a
prevalence of 4.8% (95% CI: 2.1-9.2%). Mixed infections with up to five species
were present in 27.4% (95% CI: 21-35%) of the koalas, which was significantly
higher than the prevalence of single infections 4.8% (95% CI: 2-9%). Overall, a
considerably higher proportion (79.7%) of the Trypanosoma sequences isolated from
koala blood samples were identified as T. irwini, suggesting this is the dominant
species. Co-infections involving T. gilletti, T. irwini, T. copemani, T.
vegrandis and Trypanosoma sp. AB-2017 were also detected in ticks, with T.
gilletti and T. copemani being the dominant species within the invertebrate
hosts. Direct Sanger sequencing of Trypanosoma 18S rRNA gene amplicons was also
performed and results revealed that this method was only able to identify the
genotypes with greater amount of reads (according to NGS) within koala samples,
which highlights the advantages of NGS in detecting mixed infections. The present
study provides new insights on the natural genetic diversity of Trypanosoma
communities infecting koalas and constitutes a benchmark for future clinical and
epidemiological studies required to quantify the contribution of trypanosome
infections on koala survival rates.
PMID- 28704542
TI - Conventional alpha beta (alphabeta) T cells do not contribute to acute intestinal
ischemia-reperfusion injury in mice.
AB - PURPOSE: Ischemia-reperfusion injury (IRI) is associated with significant patient
mortality and morbidity. The complex cascade of IRI is incompletely understood,
but inflammation is known to be a key mediator. In addition to the predominant
innate immune responses, previous research has also indicated that alphabeta T
cells contribute to IRI in various organ models. The aim of this study was to
clarify the role alphabeta T cells play in IRI to the gut. METHODS: Adult wild
type (WT) and alphabeta T cell-deficient mice were subjected to acute intestinal
IRI with 30min ischemia followed by 4h reperfusion. The gene expression of pro
inflammatory cytokines was measured by qPCR, and the influx of leukocyte
subpopulations in the gut was assessed via flow cytometry and histology. Pro
inflammatory cytokines in the serum were measured, and transaminases were
assessed as an indicator of distant organ IRI. RESULTS: Intestinal IRI led to an
increased expression of pro-inflammatory cytokines in the gut tissue and an
influx of leukocytes that predominantly consisted of neutrophils and macrophages.
Furthermore, intestinal IRI increased serum IL-6, TNF-alpha, and ALT/AST levels.
The alphabeta T cell-deficient mice did not exhibit a more significant increase
in pro-inflammatory cytokines in the gut or serum following IR than the WT mice.
There was also no difference between WT- and alphabeta T cell-deficient mice in
terms of neutrophil infiltration or macrophage activation. Furthermore, the
increase in transaminases was equal in both groups indicating that the level of
distant organ injury was comparable. CONCLUSION: An increasing body of evidence
demonstrates that alphabeta T cells play a key role in IRI. In the gut, however,
alphabeta T cells are not pivotal in the first hours following acute IRI as
deficiency does not impact cytokine production, neutrophil recruitment,
macrophage activation, or distant organ injury. Thus, alphabeta T cells may be
considered innocent bystanders during the acute phase of intestinal IRI.
PMID- 28704543
TI - The transcriptional regulator SsrB is involved in a molecular switch controlling
virulence lifestyles of Salmonella.
AB - The evolution of bacterial pathogenicity, heavily influenced by horizontal gene
transfer, provides new virulence factors and regulatory connections that alter
bacterial phenotypes. Salmonella pathogenicity islands 1 and 2 (SPI-1 and SPI-2)
are chromosomal regions that were acquired at different evolutionary times and
are essential for Salmonella virulence. In the intestine of mammalian hosts,
Salmonella expresses the SPI-1 genes that mediate its invasion to the gut
epithelium. Once inside the cells, Salmonella down-regulates the SPI-1 genes and
induces the expression of the SPI-2 genes, which favor its intracellular
replication. The mechanism by which the invasion machinery is deactivated
following successful invasion of host cells is not known. Here, we show that the
SPI-2 encoded transcriptional regulator SsrB, which positively controls SPI-2,
acts as a dual regulator that represses expression of SPI-1 during intracellular
stages of infection. The mechanism of this SPI-1 repression by SsrB was direct
and acts upon the hilD and hilA regulatory genes. The phenotypic effect of this
molecular switch activity was a significant reduction in invasion ability of S.
enterica serovar Typhimurium while promoting the expression of genes required for
intracellular survival. During mouse infections, Salmonella mutants lacking SsrB
had high levels of hilA (SPI-1) transcriptional activity whereas introducing a
constitutively active SsrB led to significant hilA repression. Thus, our results
reveal a novel SsrB-mediated mechanism of transcriptional crosstalk between SPI-1
and SPI-2 that helps Salmonella transition to the intracellular lifestyle.
PMID- 28704544
TI - Effect of acute ozone exposure on the lung metabolomes of obese and lean mice.
AB - Pulmonary responses to the air pollutant, ozone, are increased in obesity. Both
obesity and ozone cause changes in systemic metabolism. Consequently, we examined
the impact of ozone on the lung metabolomes of obese and lean mice. Lean wildtype
and obese db/db mice were exposed to acute ozone (2 ppm for 3 h) or air. 24 hours
later, the lungs were excised, flushed with PBS to remove blood and analyzed via
liquid-chromatography or gas-chromatography coupled to mass spectrometry for
metabolites. Both obesity and ozone caused changes in the lung metabolome. Of 321
compounds identified, 101 were significantly impacted by obesity in air-exposed
mice. These included biochemicals related to carbohydrate and lipid metabolism,
which were each increased in lungs of obese versus lean mice. These metabolite
changes may be of functional importance given the signaling capacity of these
moieties. Ozone differentially affected the lung metabolome in obese versus lean
mice. For example, almost all phosphocholine-containing lysolipids were
significantly reduced in lean mice, but this effect was attenuated in obese mice.
Glutathione metabolism was also differentially affected by ozone in obese and
lean mice. Finally, the lung metabolome indicated a role for the microbiome in
the effects of both obesity and ozone: all measured bacterial/mammalian co
metabolites were significantly affected by obesity and/or ozone. Thus, metabolic
derangements in obesity appear to impact the response to ozone.
PMID- 28704545
TI - An overview of genetic rust resistance: From broad to specific mechanisms.
PMID- 28704546
TI - Epidemiology of Staphylococcus aureus in a burn unit of a tertiary care center in
Ghana.
AB - BACKGROUND: In developing countries, hospitalized burn victims are at high risk
of nosocomial infections caused by Staphylococcus aureus. Risk factors include
poor infection control practices, prolonged hospitalisation and limited capacity
for laboratory microbiological analyses. These problems are compounded by
widespread use of antibiotics that drives the spread of multi-drug resistant
bacteria. METHODS: During the study period (November 2014-June 2015), nasal and
invasive S. aureus isolates were collected consecutively from patients and
healthcare workers (HCWs) within the burn unit of the Reconstructive Plastic
Surgery and Burn Center of Korle Bu Teaching Hospital in Ghana. Antibiotic
prescription, antibiotic susceptibility and bacterial typing were used to assess
antibiotic pressure, antibiotic resistance, and possible transmission events
among patients and HCWs. RESULTS: Eighty S. aureus isolates were obtained from 37
of the 62 included burn patients and 13 of the 29 HCWs. At admission, 50% of
patients carried or were infected with S. aureus including methicillin resistant
S. aureus (MRSA). Antibiotic use per 100 days of hospitalization was high (91.2
days), indicating high selective pressure for resistant pathogens. MRSA isolates
obtained from 11 patients and one HCW belonged to the same spa-type t928 and
multi-locus sequence type 250, implying possible transmission events. A mortality
rate of 24% was recorded over the time of admission in the burn unit. CONCLUSION:
This study revealed a high potential for MRSA outbreaks and emergence of
resistant pathogens amongst burn patients due to lack of patient screening and
extended empirical use of antibiotics. Our observations underscore the need to
implement a system of antibiotic stewardship and infection prevention where
microbiological diagnostics results are made available to physicians for timely
and appropriate patient treatment.
PMID- 28704547
TI - What viruses can teach us about the human immune system.
PMID- 28704548
TI - Socio-economic predictors of stillbirths in Nepal (2001-2011).
AB - INTRODUCTION: Stillbirth has a long-lasting impact on parents and families. This
study examined socio-economic predictors associated with stillbirth in Nepal for
the year 2001, 2006 and 2011. METHODS: The Nepalese Demographic and Health Survey
(NDHS) data for the period (2001-2011) were pooled to estimate socio-economic
predictors associated with stillbirths in Nepal using binomial logistic
regression while taking clustering and sampling weights into account. RESULTS: A
total of 18,386 pregnancies of at least 28 weeks gestation were identified. Of
these pregnancies, 335 stillbirths were reported. Stillbirth increased
significantly among women that lived in the hills ecological zones (aRR 1.38, 95%
CI 1.02, 1.87) or in the mountains ecological zones (aRR 1.71, 95% CI 1.10,
2.66). Women with no schooling (aRR 1.72, 95% CI 1.10, 2.69), women with primary
education (aRR 1.81, 95% CI 1.11, 2.97); open defecation (aRR 1.48, 95% CI 1.00,
2.18), and those whose major occupation was agriculture (aRR 1.80, 95% CI 1.16,
2.78) are more likely to report higher stillbirth. CONCLUSIONS: Low levels of
education, ecological zones and open defecation were found to be strong
predictors of stillbirth. Access to antenatal care services and skilled birth
attendants for women in the mountainous and hilly ecological zones of Nepal is
needed to further reduce stillbirth and improved services should also focus on
women with low levels of education.
PMID- 28704549
TI - Correction: Molecular exploration of hidden diversity in the Indo-West Pacific
sciaenid clade.
AB - [This corrects the article DOI: 10.1371/journal.pone.0176623.].
PMID- 28704550
TI - Is it appropriate for Korean women to adopt the 2009 Institute of Medicine
recommendations for gestational weight gain?
AB - BACKGROUND: The 2009 Institute of Medicine (IOM) guidelines for gestational
weight gain (GWG) are intended for use among women in the United States. Little
data are available on whether the 2009 IOM recommendations can be applied to
Asian women. This study aimed to evaluate whether the recommendations are related
to adverse pregnancy outcomes in Korean pregnant women. METHODS AND FINDINGS: A
retrospective cohort study was conducted for all singleton-pregnant women at a
university hospital in Korea. After classifying the enrolled women into four
Korean pre-pregnancy body mass index (BMI) categories, the risk of adverse
pregnancy outcomes were analyzed for women who gained inadequate or excessive GWG
based on 2009 IOM recommendations. Of 7,843 pregnancies, 64.0% of women had
normal pre-pregnancy BMI and 42.7% achieved optimal GWG. Across all BMI
categories, adverse pregnancies outcomes such as small for gestational age (SGA),
large for gestational age (LGA), preterm birth, preeclampsia, and cesarean due to
dystocia were significantly associated with GWG (all P <= 0.001).Women with
normal BMI who gained inadequate weight were more likely to develop SGA and
preterm birth and less likely to develop LGA (adjusted odds ratio (aOR) 2.21,
1.33, and 0.54, respectively). Whereas, women with normal BMI who gained
excessive weight were more likely to develop LGA, preterm birth, preeclampsia,
and cesarean section due to dystocia (aOR 2.10, 1.33, 1.37, and 1.37,
respectively) and less likely to develop SGA (aOR 0.60). CONCLUSIONS: It is
tolerable for Korean women to follow recommended GWG from the 2009 IOM guidelines
to decrease adverse pregnancy outcomes. This will be helpful for antenatal care
on GWG not only for Korean pregnant women, but also other Asian women who have
lower BMI criteria than Caucasian women.
PMID- 28704551
TI - Opposing roles of Toll-like receptor and cytosolic DNA-STING signaling pathways
for Staphylococcus aureus cutaneous host defense.
AB - Successful host defense against pathogens requires innate immune recognition of
the correct pathogen associated molecular patterns (PAMPs) by pathogen
recognition receptors (PRRs) to trigger the appropriate gene program tailored to
the pathogen. While many PRR pathways contribute to the innate immune response to
specific pathogens, the relative importance of each pathway for the complete
transcriptional program elicited has not been examined in detail. Herein, we used
RNA-sequencing with wildtype and mutant macrophages to delineate the innate
immune pathways contributing to the early transcriptional response to
Staphylococcus aureus, a ubiquitous microorganism that can activate a wide
variety of PRRs. Unexpectedly, two PRR pathways-the Toll-like receptor (TLR) and
Stimulator of Interferon Gene (STING) pathways-were identified as dominant
regulators of approximately 95% of the genes that were potently induced within
the first four hours of macrophage infection with live S. aureus. TLR signaling
predominantly activated a pro-inflammatory program while STING signaling
activated an antiviral/type I interferon response with live but not killed S.
aureus. This STING response was largely dependent on the cytosolic DNA sensor
cyclic guanosine-adenosine synthase (cGAS). Using a cutaneous infection model, we
found that the TLR and STING pathways played opposite roles in host defense to S.
aureus. TLR signaling was required for host defense, with its absence reducing
interleukin (IL)-1beta production and neutrophil recruitment, resulting in
increased bacterial growth. In contrast, absence of STING signaling had the
opposite effect, enhancing the ability to restrict the infection. These results
provide novel insights into the complex interplay of innate immune signaling
pathways triggered by S. aureus and uncover opposing roles of TLR and STING in
cutaneous host defense to S. aureus.
PMID- 28704552
TI - PTCH1 is a reliable marker for predicting imatinib response in chronic myeloid
leukemia patients in chronic phase.
AB - Patched homolog 1 gene (PTCH1) expression and the ratio of PTCH1 to Smoothened
(SMO) expression have been proposed as prognostic markers of the response of
chronic myeloid leukemia (CML) patients to imatinib. We compared these
measurements in a realistic cohort of 101 patients with CML in chronic phase (CP)
using a simplified qPCR method, and confirmed the prognostic power of each in a
competing risk analysis. Gene expression levels were measured in peripheral blood
samples at diagnosis. The PTCH1/SMO ratio did not improve PTCH1 prognostic power
(area under the receiver operating characteristic curve 0.71 vs. 0.72). In order
to reduce the number of genes to be analyzed, PTCH1 was the selected measurement.
High and low PTCH1 expression groups had significantly different cumulative
incidences of imatinib failure (IF), which was defined as discontinuation of
imatinib due to lack of efficacy (5% vs. 25% at 4 years, P = 0.013),
probabilities of achieving a major molecular response (81% vs. 53% at first year,
P = 0.02), and proportions of early molecular failure (14% vs. 43%, P = 0.015).
Every progression to an advanced phase (n = 3) and CML-related death (n = 2)
occurred in the low PTCH1 group (P<0.001 for both comparisons). PTCH1 was an
independent prognostic factor for the prediction of IF. We also validated
previously published thresholds for PTCH1 expression. Therefore, we confirmed
that PTCH1 expression can predict the imatinib response in CML patients in CP by
applying a more rigorous statistical analysis. Thus, PTCH1 expression is a
promising molecular marker for predicting the imatinib response in CML patients
in CP.
PMID- 28704553
TI - Screening and characterizing of xylanolytic and xylose-fermenting yeasts isolated
from the wood-feeding termite, Reticulitermes chinensis.
AB - The effective fermentation of xylose remains an intractable challenge in
bioethanol industry. The relevant xylanase enzyme is also in a high demand from
industry for several biotechnological applications that inevitably in recent
times led to many efforts for screening some novel microorganisms for better
xylanase production and fermentation performance. Recently, it seems that wood
feeding termites can truly be considered as highly efficient natural bioreactors.
The highly specialized gut systems of such insects are not yet fully realized,
particularly, in xylose fermentation and xylanase production to advance
industrial bioethanol technology as well as industrial applications of xylanases.
A total of 92 strains from 18 yeast species were successfully isolated and
identified from the gut of wood-feeding termite, Reticulitermes chinensis. Of
these yeasts and strains, seven were identified for new species: Candida gotoi,
Candida pseudorhagii, Hamamotoa lignophila, Meyerozyma guilliermondii,
Sugiyamaella sp.1, Sugiyamaella sp. 2, and Sugiyamaella sp.3. Based on the
phylogenetic and phenotypic characterization, the type strain of C. pseudorhagii
sp. nov., which was originally designated strain SSA-1542T, was the most
frequently occurred yeast from termite gut samples, showed the highly xylanolytic
activity as well as D-xylose fermentation. The highest xylanase activity was
recorded as 1.73 and 0.98 U/mL with xylan or D-xylose substrate, respectively,
from SSA-1542T. Among xylanase-producing yeasts, four novel species were
identified as D-xylose-fermenting yeasts, where the yeast, C. pseudorhagii SSA
1542T, showed the highest ethanol yield (0.31 g/g), ethanol productivity (0.31
g/L.h), and its fermentation efficiency (60.7%) in 48 h. Clearly, the symbiotic
yeasts isolated from termite guts have demonstrated a competitive capability to
produce xylanase and ferment xylose, suggesting that the wood-feeding termite gut
is a promising reservoir for novel xylanases-producing and xylose-fermenting
yeasts that are potentially valued for biorefinery industry.
PMID- 28704554
TI - Trends in the incidence and outcomes of bicycle-related injury in the emergency
department: A nationwide population-based study in South Korea, 2012-2014.
AB - OBJECTIVE: This study aimed to examine trends in the incidence and outcomes of
bicycle-related injuries in emergency departments (ED) in South Korea. METHODS:
We analysed data from the National Emergency Department Information System
database for adult patients (>=20 years) with bicycle-related injuries presenting
to EDs in South Korea between January 2012 and December 2014. Riders and bicycle
passengers whose injuries were associated with bicycle use were included. Serious
outcomes were defined as death at the ED, need for emergency operation, or
intensive care unit admission. RESULTS: The number of people who commute to work
by bicycle increased by 36% from 205,100 in 2005 to 279,544 in 2015. Of 529,278
traffic-related trauma cases, 58,352 (11.0%) were bicycle-related, which
increased from 7,894 (10.2%) in the first half of 2012 to 12,882 (12.2%) in the
second half of 2014 (p < 0.001). However, the proportion of serious outcomes
decreased from 5.0% to 4.2% during the study period (p < 0.001). Serious outcomes
were most frequent in the elderly (65-74 years) and older elderly (>=75 years)
groups and decreased for all but the elderly age group from 10.3% to 9.8% (p =
0.204). The helmet use rate increased from 14.2% to 20.3% (p < 0.001) but was the
lowest in the older elderly group (3.6%) without change during the study period
(from 4.7% to 3.7%, p = 0.656). A lack of helmet use was significantly associated
with serious outcomes (odds ratio, 1.811; 95% confidence interval, 1.576-2.082).
CONCLUSIONS: Although the incidence of bicycle-related injuries increased, the
proportion of serious outcomes decreased, possibly due to increased helmet use.
Public education on safety equipment use is required, especially in elderly
populations.
PMID- 28704555
TI - A system model of the effects of exercise on plasma Interleukin-6 dynamics in
healthy individuals: Role of skeletal muscle and adipose tissue.
AB - Interleukin-6 (IL-6) has been recently shown to play a central role in glucose
homeostasis, since it stimulates the production and secretion of Glucagon-like
Peptide-1 (GLP-1) from intestinal L-cells and pancreas, leading to an enhanced
insulin response. In resting conditions, IL-6 is mainly produced by the adipose
tissue whereas, during exercise, skeletal muscle contractions stimulate a marked
IL-6 secretion as well. Available mathematical models describing the effects of
exercise on glucose homeostasis, however, do not account for this IL-6
contribution. This study aimed at developing and validating a system model of
exercise's effects on plasma IL-6 dynamics in healthy humans, combining the
contributions of both adipose tissue and skeletal muscle. A two-compartment
description was adopted to model plasma IL-6 changes in response to oxygen
uptake's variation during an exercise bout. The free parameters of the model were
estimated by means of a cross-validation procedure performed on four different
datasets. A low coefficient of variation (<10%) was found for each parameter and
the physiologically meaningful parameters were all consistent with literature
data. Moreover, plasma IL-6 dynamics during exercise and post-exercise were
consistent with literature data from exercise protocols differing in intensity,
duration and modality. The model successfully emulated the physiological effects
of exercise on plasma IL-6 levels and provided a reliable description of the role
of skeletal muscle and adipose tissue on the dynamics of plasma IL-6. The system
model here proposed is suitable to simulate IL-6 response to different exercise
modalities. Its future integration with existing models of GLP-1-induced insulin
secretion might provide a more reliable description of exercise's effects on
glucose homeostasis and hence support the definition of more tailored
interventions for the treatment of type 2 diabetes.
PMID- 28704556
TI - A comparative study revealed first insights into the diversity and metabolisms of
the microbial communities in the sediments of Pacmanus and Desmos hydrothermal
fields.
AB - Currently, little is known about the microbial diversity in the sediments of
Pacmanus and Desmos hydrothermal fields in Manus Basin. In this study, Illumina
based sequencing of 16S rRNA gene amplicons and metagenomic analysis were
conducted to investigate the microbial populations and metabolic profiles in the
sediments from four different regions in Pacmanus and Desmos hydrothermal fields.
It was found that Gammaproteobacteria and Thaumarchaeota were the most abundant
bacterial and archaeal populations, respectively. The autotrophic prokaryotes in
the four communities probably fixed CO2 via four major pathways, i.e. Calvin
Benson-Bassham cycle, reductive acetyl-CoA cycle, rTCA cycle, and 3
hydroxypropionate/4-hydroxybutyrate cycle. Ammonia-oxidizing Thaumarchaeota,
nitrifiers, denitrifiers, and sulfur oxidizers belonging to the subgroups of
Proteobacteria (e.g., alpha, beta, gamma, and epsilon), Nitrospira, and
Nitrospina, and sulfate-reducing Desulfobacterales likely played critical roles
in nitrogen and sulfur cycling, in which ammonia, sulfur compounds, and hydrogen
could be utilized as potential energy sources. These findings revealed new
insights into the operational mechanism of the microbial communities associated
with Pacmanus and Desmos hydrothermal fields.
PMID- 28704557
TI - Monte Carlo studies on neutron interactions in radiobiological experiments.
AB - Monte Carlo method was used to study the characteristics of neutron interactions
with cells underneath a water medium layer with varying thickness. The following
results were obtained. (1) The fractions of neutron interaction with 1H, 12C, 14N
and 16O nuclei in the cell layer were studied. The fraction with 1H increased
with increasing medium thickness, while decreased for 12C, 14N and 16O nuclei.
The bulges in the interaction fractions with 12C, 14N and 16O nuclei were
explained by the resonance spikes in the interaction cross-section data. The
interaction fraction decreased in the order: 1H > 16O > 12C > 14N. (2) In
general, as the medium thickness increased, the number of "interacting neutrons"
which exited the medium and then further interacted with the cell layer
increased. (3) The area under the angular distributions for "interacting
neutrons" decreased with increasing incident neutron energy. Such results would
be useful for deciphering the reasons behind discrepancies among existing results
in the literature.
PMID- 28704558
TI - Correction: Cone-beam computed tomography with automated bone subtraction in
preoperative embolization for pelvic bone tumors.
AB - [This corrects the article DOI: 10.1371/journal.pone.0175907.].
PMID- 28704559
TI - Synthesis, cytotoxicity and antitumour mechanism investigations of
polyoxometalate doped silica nanospheres on breast cancer MCF-7 cells.
AB - Polyoxometalates (POMs) have shown the potential anti-bacterial, anti-viral and
anti-tumor activities. In order to improve their physiological stability and
antitumour activity for medical application, K2Na[AsIIIMo6O21(O2CCH2NH3)3].6H2O
doped silica nanospheres (POM@SiO2) with diameters of ~40 nm have been
synthesized by the water-in-oil microemulsion method in this study. The obtained
spheres were morphologically uniform nanosized and nearly monodispersed in
solution. The nanoparticles had high entrapment efficiency, which was upto 46.2%
by the inductively coupled plasma mass spectrometry (ICP-MS) analysis and POMs
slowly released from the nanospheres both in the PH 7.4 and 5.5 phosphate buffer
saline (PBS) solutions in 60 h. The in vitro MTT assays of particles on MCF-7
cell line (a human breast adenocarcinoma cell line) exhibited enhanced antitumor
activity compared to that of plain polyoxometalate. The IC50 value of the
POM@SiO2 nanoparticles was 40.0 MUg/mL at 24 h calculated by the encapsulated POM
concentration, which was much lower comparing to that of 2.0 * 104 MUg/mL
according to the pure POM. And the SiO2 shells showed low inhibitory effect at
the corresponding concentration. Confocal images further indicated the cell
morphology changes and necrosis. Flow cytometric analysis showed nanoparticles
induced the apoptosis by arresting the cells in S phase and western blot analysis
indicated they promoted apoptosis by inhibiting the Bcl-2 protein. Moreover, the
study of interactions between human serum albumin (HSA) and the nanoparticles
indicated the fluorescence quenching was static, and the nanoparticles were
likely to bind to HSA and changed its conformation.
PMID- 28704560
TI - Performance characteristics of finger-stick dried blood spots (DBS) on the
determination of human immunodeficiency virus (HIV) treatment failure in a
pediatric population in Mozambique.
AB - Quantitative plasma viral load (VL) at 1000 copies /mL was recommended as the
threshold to confirm antiretroviral therapy (ART) failure by the World Health
Organization (WHO). Because of ongoing challenges of using plasma for VL testing
in resource-limited settings (RLS), especially for children, this study collected
717 DBS and paired plasma samples from children receiving ART >=1 year in
Mozambique and compared the performance of DBS using Abbott's VL test with a
paired plasma sample using Roche's VL test. At a cut-off of 1000 copies/mL,
sensitivity of DBS using Abbott DBS VL test was 79.9%, better than 71.0% and
63.9% at 3000 and 5000 copies/mL, respectively. Specificities were 97.6%, 98.8%,
99.3% at 1000, 3000, and 5000 copies/mL, respectively. The Kappa value at 1000
copies/mL, 0.80 (95% CI: 0.73, 0.87), was higher than 0.73 (95% CI: 0.66, 0.80)
and 0.66 (95% CI: 0.59, 0.73) at 3000, 5000 copies/mL, respectively, also
indicating better agreement. The mean difference between the DBS and plasma VL
tests with 95% limits of agreement by Bland-Altman was 0.311 (-0.908, 1.530).
Among 73 children with plasma VL between 1000 to 5000 copies/mL, the DBS results
were undetectable in 53 at the 1000 copies/mL threshold. While one DBS sample in
the Abbott DBS VL test may be an alternative method to confirm ART failure at
1000 copies/mL threshold when a plasma sample is not an option for treatment
monitoring, because of sensitivity concerns between 1,000 and 5,000 copies/ml,
two DBS samples may be preferred accompanied by careful patient monitoring and
repeat testing.
PMID- 28704561
TI - Diet overlap and spatial segregation between two neotropical marsupials revealed
by multiple analytical approaches.
AB - Species co-existence depends on how organisms utilize their environment and
resources. When two sympatric species are similar in some ecological
requirements, their coexistence may arise from differences in resource use over
time and/or space. Interactions among coexisting marsupials remain poorly
understood, especially in the Neotropics. Here we combine spatial niche
measurements, individual-resource networks, and isotopic niche approaches, to
investigate the ecological strategies used by the Neotropical marsupials
Didelphis aurita and Metachirus nudicaudatus to co-occur in an area of Serra do
Mar State Park (southeast of Brazil). Both individual-resource networks and
isotopic niche approaches indicate similar patterns of omnivory for both species.
Isotopic analysis showed the species' trophic niche to be similar, with 52% of
overlap, and no differences between proportional contributions of each resource
to their diets. Moreover, individual-resource network analysis found no evidence
of diet nestedness or segregation. The trophic niche overlap observed was
associated with spatial segregation between species. Despite using the same area
over the year, D. aurita and M. nudicaudatus exhibited spatial segregation among
seasons. These results illustrate that the detection of spatial segregation is
scale-dependent and must be carefully considered. In conclusion, our findings
provide a new perspective on the ecology of these two Neotropical marsupials by
illustrating how the association of distinct but complementary methods can be
applied to reach a more complete understanding of resource partitioning and
species coexistence.
PMID- 28704562
TI - Cerebral 18F-FDG PET in macrophagic myofasciitis: An individual SVM-based
approach.
AB - INTRODUCTION: Macrophagic myofasciitis (MMF) is an emerging condition with highly
specific myopathological alterations. A peculiar spatial pattern of a cerebral
glucose hypometabolism involving occipito-temporal cortex and cerebellum have
been reported in patients with MMF; however, the full pattern is not
systematically present in routine interpretation of scans, and with varying
degrees of severity depending on the cognitive profile of patients. Aim was to
generate and evaluate a support vector machine (SVM) procedure to classify
patients between healthy or MMF 18F-FDG brain profiles. METHODS: 18F-FDG PET
brain images of 119 patients with MMF and 64 healthy subjects were
retrospectively analyzed. The whole-population was divided into two groups; a
training set (100 MMF, 44 healthy subjects) and a testing set (19 MMF, 20 healthy
subjects). Dimensionality reduction was performed using a t-map from statistical
parametric mapping (SPM) and a SVM with a linear kernel was trained on the
training set. To evaluate the performance of the SVM classifier, values of
sensitivity (Se), specificity (Sp), positive predictive value (PPV), negative
predictive value (NPV) and accuracy (Acc) were calculated. RESULTS: The SPM12
analysis on the training set exhibited the already reported hypometabolism
pattern involving occipito-temporal and fronto-parietal cortices, limbic system
and cerebellum. The SVM procedure, based on the t-test mask generated from the
training set, correctly classified MMF patients of the testing set with following
Se, Sp, PPV, NPV and Acc: 89%, 85%, 85%, 89%, and 87%. CONCLUSION: We developed
an original and individual approach including a SVM to classify patients between
healthy or MMF metabolic brain profiles using 18F-FDG-PET. Machine learning
algorithms are promising for computer-aided diagnosis but will need further
validation in prospective cohorts.
PMID- 28704563
TI - Self-propagating, protease-resistant, recombinant prion protein conformers with
or without in vivo pathogenicity.
AB - Prions, characterized by self-propagating protease-resistant prion protein (PrP)
conformations, are agents causing prion disease. Recent studies generated several
such self-propagating protease-resistant recombinant PrP (rPrP-res) conformers.
While some cause prion disease, others fail to induce any pathology. Here we
showed that although distinctly different, the pathogenic and non-pathogenic rPrP
res conformers were similarly recognized by a group of conformational antibodies
against prions and shared a similar guanidine hydrochloride denaturation profile,
suggesting a similar overall architecture. Interestingly, two independently
generated non-pathogenic rPrP-res were almost identical, indicating that the
particular rPrP-res resulted from cofactor-guided PrP misfolding, rather than
stochastic PrP aggregation. Consistent with the notion that cofactors influence
rPrP-res conformation, the propagation of all rPrP-res formed with
phosphatidylglycerol/RNA was cofactor-dependent, which is different from rPrP-res
generated with a single cofactor, phosphatidylethanolamine. Unexpectedly, despite
the dramatic difference in disease-causing capability, RT-QuIC assays detected
large increases in seeding activity in both pathogenic and non-pathogenic rPrP
res inoculated mice, indicating that the non-pathogenic rPrP-res is not
completely inert in vivo. Together, our study supported a role of cofactors in
guiding PrP misfolding, indicated that relatively small structural features
determine rPrP-res' pathogenicity, and revealed that the in vivo seeding ability
of rPrP-res does not necessarily result in pathogenicity.
PMID- 28704564
TI - Poor clinical response in rheumatoid arthritis is the main risk factor for
diabetes development in the short-term: A 1-year, single-centre, longitudinal
study.
AB - OBJECTIVES: Despite of the European League Against Rheumatism (EULAR) provided
different sets of recommendations for the management of cardiovascular risk in
inflammatory arthritis patients, it must be pointed out that cardiometabolic
comorbidity, such as type 2 diabetes (T2D), remains still underdiagnosed and
undertreated in patients affected by rheumatoid arthritis (RA). METHODS: In this
work, we designed a single centre, prospective study in order to better
investigate the occurrence of T2D during the course of 1 year of follow-up.
Furthermore, we evaluated the role of both traditional cardiovascular and RA
specific related risk factors to predict the occurrence of new T2D. RESULTS: In
this study, we evaluated 439 consecutive RA patients and we observed that 7.1% of
our patients (31/439) developed T2D, after 12 month of prospective follow-up. The
regression analysis showed that the presence of high blood pressure, the impaired
fasting glucose (IFG) at the first observation and the poor EULAR-DAS28 response,
after 12 months of follow-up, were significantly associated with an increased
likelihood of being classified as T2D. Similarly, we observed that 7.7% of our
patients (34/439) showed IFG after 12 months of prospective follow-up. The
regression analysis showed that the presence of high blood pressure and the poor
EULAR-DAS28 response after 12 months of follow-up, were significantly associated
with an increased likelihood of showing IFG. CONCLUSIONS: Our study supports the
hypothesis of a significant short-term risk of T2D in RA patients and of a close
associations between uncontrolled disease activity and glucose metabolism
derangement. Further multicentre, randomised-controlled studies are surely needed
in order to elucidate these findings and to better ascertain the possible
contribution of different therapeutic regimens to reduce this risk.
PMID- 28704565
TI - Contribution of seagrass plants to CO2 capture in a tropical seagrass meadow
under experimental disturbance.
AB - Coastal vegetative habitats are known to be highly productive environments with a
high ability to capture and store carbon. During disturbance this important
function could be compromised as plant photosynthetic capacity, biomass, and/or
growth are reduced. To evaluate effects of disturbance on CO2 capture in plants
we performed a five-month manipulative experiment in a tropical seagrass
(Thalassia hemprichii) meadow exposed to two intensity levels of shading and
simulated grazing. We assessed CO2 capture potential (as net CO2 fixation) using
areal productivity calculated from continuous measurements of diel photosynthetic
rates, and estimates of plant morphology, biomass and productivity/respiration
(P/R) ratios (from the literature). To better understand the plant capacity to
coping with level of disturbance we also measured plant growth and resource
allocation. We observed substantial reductions in seagrass areal productivity,
biomass, and leaf area that together resulted in a negative daily carbon balance
in the two shading treatments as well as in the high-intensity simulated grazing
treatment. Additionally, based on the concentrations of soluble carbohydrates and
starch in the rhizomes, we found that the main reserve sources for plant growth
were reduced in all treatments except for the low-intensity simulated grazing
treatment. If permanent, these combined adverse effects will reduce the plants'
resilience and capacity to recover after disturbance. This might in turn have
long-lasting and devastating effects on important ecosystem functions, including
the carbon sequestration capacity of the seagrass system.
PMID- 28704566
TI - Development and characterization of a human three-dimensional chondrosarcoma
culture for in vitro drug testing.
AB - It has been suggested that chemoresistance of chondrosarcoma (CHS), the cartilage
tumor, is caused by the phenotypic microenvironmental features of the tumor
tissue, mainly the chondrogenic extracellular matrix (ECM), and hypoxia. We
developed and characterized a multicellular tumor spheroid (MCTS) of human
chondrosarcoma HEMC-SS cells to gain insight into tumor cell biology and drug
response. At Day 7, HEMC-SS spheroids exhibited a homogeneous distribution of
proliferative Ki-67 positive cells, whereas in larger spheroids (Day 14 and Day
20), proliferation was mainly localized in the periphery. In the core of larger
spheroids, apoptotic cells were evidenced by TUNEL assay, and hypoxia by
pimonidazole staining. Interestingly, VEGF excretion, evidenced by ELISA on
culture media, was detectable from Day 14 spheroids, and increased as the
spheroids grew in size. HEMC-SS spheroids synthesized a chondrogenic
extracellular matrix rich in glycosaminoglycans and type-2 collagen. Finally, we
investigated the sensitivity of Day 7 and Day 14 chondrosarcoma MCTS to hypoxia
activated prodrug TH-302 and doxorubicin compared with their 2D counterparts. As
expected, TH-302 exhibited higher cytotoxic activity on larger hypoxic spheroids
(Day 14) than on non-hypoxic spheroids (Day 7), with multicellular resistance
index (MCRI) values of 7.7 and 9.1 respectively. For doxorubicin, the larger
sized spheroids exhibited higher drug resistance (MCRI of 5.0 for Day 7 and 18.3
for Day 14 spheroids), possibly due to impeded drug penetration into the deep
layer of spheroids, evidenced by its auto-fluorescence property. We have
developed a model of human chondrosarcoma MCTS that combines an ECM rich in
glycosaminoglycans with a high hypoxic core associated with VEGF excretion. This
model could offer a more predictive in vitro chondrosarcoma system for screening
drugs targeting tumor cells and their microenvironment.
PMID- 28704567
TI - Correction: In Vivo Persistence of Human Rhinoviruses in Immunosuppressed
Patients.
AB - [This corrects the article DOI: 10.1371/journal.pone.0170774.].
PMID- 28704568
TI - Correction: Tissue factor pathway inhibitor for prediction of placenta-mediated
adverse pregnancy outcomes in high-risk women: AngioPred study.
AB - [This corrects the article DOI: 10.1371/journal.pone.0173596.].
PMID- 28704569
TI - A virulence-associated filamentous bacteriophage of Neisseria meningitidis
increases host-cell colonisation.
AB - Neisseria meningitidis is a commensal of human nasopharynx. In some
circumstances, this bacteria can invade the bloodstream and, after crossing the
blood brain barrier, the meninges. A filamentous phage, designated MDAPhi for
Meningococcal Disease Associated, has been associated with invasive disease. In
this work we show that the prophage is not associated with a higher virulence
during the bloodstream phase of the disease. However, looking at the interaction
of N. meningitidis with epithelial cells, a step essential for colonization of
the nasopharynx, we demonstrate that the presence of the prophage, via the
production of viruses, increases colonization of encapsulated meningococci onto
monolayers of epithelial cells. The analysis of the biomass covering the
epithelial cells revealed that meningococci are bound to the apical surface of
host cells by few layers of heavily piliated bacteria, whereas, in the upper
layers, bacteria are non-piliated but surrounded by phage particles which (i)
form bundles of filaments, and/or (ii) are in some places associated with
bacteria. The latter are likely to correspond to growing bacteriophages during
their extrusion through the outer membrane. These data suggest that, as the
biomass increases, the loss of piliation in the upper layers of the biomass does
not allow type IV pilus bacterial aggregation, but is compensated by a large
production of phage particles that promote bacterial aggregation via the
formation of bundles of phage filaments linked to the bacterial cell walls. We
propose that MDAPhi by increasing bacterial colonization in the mucosa at the
site-of-entry, increase the occurrence of diseases.
PMID- 28704570
TI - Signs of eclampsia during singleton deliveries and early neonatal mortality in
low- and middle-income countries from three WHO regions.
AB - OBJECTIVE: To determine the prevalence of eclampsia symptoms and to explore
associations between eclampsia and early neonatal mortality. METHODS: The present
secondary analysis included Demographic and Health Surveys data from 2005 to
2012; details of signs related to severe obstetric adverse events of singleton
deliveries during interviewees' most recent delivery in the preceding 5 years
were included. Data and delivery history were merged for pooled analyses.
Convulsions-used as an indicator for having experienced eclampsia-and early
neonatal mortality rates were compared, and a generalized random effect model,
adjusted for heterogeneity between and within countries, was used to investigate
the impact of presumed eclampsia on early neonatal mortality. RESULTS: The merged
dataset included data from six surveys and 55 384 live deliveries that occurred
in Colombia, Bangladesh, Indonesia, Mali, Niger, and Peru. Indications of
eclampsia were recorded for 1.2% (95% confidence interval [CI] 1.0-1.3), 1.7%
(95% CI 1.5-2.1), and 1.7% (95% CI 1.5-2.1) of deliveries reported from the
American, South East Asian, and African regions, respectively. Pooled analyses
demonstrated that eclampsia was associated with increased risk of early neonatal
mortality (adjusted risk ratio 2.1 95% CI 1.4-3.2). CONCLUSION: Increased risk of
early neonatal mortality indicates a need for strategies targeting the early
detection of eclampsia and early interventions.
PMID- 28704571
TI - Silver ion coordination countercurrent chromatography: Separation of beta-elemene
from the volatile oil of Curcumae Rhizoma.
AB - In this work, the antitumor constituent beta-elemene was selectively separated
from the volatile oil of the Curcumae Rhizoma by countercurrent chromatography
with silver nitrate as selective reagent based on the formation of coordination
complexes. A biphasic solvent system composed of n-hexane/methanol/water
(2:1.5:0.5, v/v/v) was selected, in which 0.15 mol/L of silver nitrate was added
to the aqueous phase. The aqueous phase was used as the stationary phase for
separation of beta-elemene by countercurrent chromatography after it was
partially purified from the volatile oil by silica gel column chromatography. An
enriched beta-elemene fraction was obtained by silica gel column chromatography
to improve the percentage of beta-elemene from 16.5 to 46.1%. Subsequently, beta
elemene was further purified from 445 mg of the partially purified sample of
volatile oil by countercurrent chromatography with silver nitrate as a selective
reagent, yielding 145 mg of beta-elemene with greater than 99% purity, as
determined by gas chromatography mass spectrometry. The recovery of beta-elemene
from the crude volatile oil through two steps was around 63.6%.
PMID- 28704572
TI - Caryophyllane Thiols, Vinyl Thioethers, Di- and Bis-Sulfides: Antioxidant and
Membrane Protective Activities.
AB - Caryophyllane thioterpenoids were synthesized in 23 - 81% yields. The antioxidant
properties of the obtained compounds in various model systems were found. It was
revealed that 4,5-epoxycaryophyll-9-ylmethanethiol has the greatest antioxidant
activity. The isomerism of sesquiterpenic fragments was shown to have a
significant effect on the biological activity of the compounds.
PMID- 28704573
TI - Modulation of Mitochondriotropic Properties of Cyanine Dyes by in Organello
Copper-Free Click Reaction.
AB - Cyanine (Cy) dyes show a general propensity to localize in polarized
mitochondria. This mitochondriotropism was used to perform a copper-free click
reaction in the mitochondria of living cells. The in organello reaction of dyes
Cy3 and Cy5 led to a product that was easily traceable by Forster resonance
energy transfer (FRET). As determined by confocal laser scanning microscopy, the
Cy3-Cy5 conjugate showed enhanced retention in mitochondria, relative to that of
the starting compounds. This enhancement of a favorable property can be achieved
by synthesis in organello, but not outside mitochondria.
PMID- 28704574
TI - A Computational Method for Unveiling the Target Promiscuity of Pharmacologically
Active Compounds.
AB - Drug discovery is governed by the desire to find ligands with defined modes of
action. It has been realized that even designated selective drugs may have more
macromolecular targets than is commonly thought. Consequently, it will be
mandatory to consider multitarget activity for the design of future medicines.
Computational models assist medicinal chemists in this effort by helping to
eliminate unsuitable lead structures and spot undesired drug effects early in the
discovery process. Here, we present a straightforward computational method to
find previously unknown targets of pharmacologically active compounds. Validation
experiments revealed hitherto unknown targets of the natural product resveratrol
and the nonsteroidal anti-inflammatory drug celecoxib. The obtained results
advocate machine learning for polypharmacology-based molecular design, drug re
purposing, and the "de-orphaning" of phenotypic drug effects.
PMID- 28704575
TI - 18 F-Labeling of Sensitive Biomolecules for Positron Emission Tomography.
AB - Positron emission tomography (PET) imaging study of fluorine-18 labeled
biomolecules is an emerging and rapidly growing area for preclinical and clinical
research. The present review focuses on recent advances in radiochemical methods
for incorporating fluorine-18 into biomolecules via "direct" or "indirect"
bioconjugation. Recently developed prosthetic groups and pre-targeting
strategies, as well as representative examples in 18 F-labeling of biomolecules
in PET imaging research studies are highlighted.
PMID- 28704577
TI - Parenting stress and development of late preterm infants at 4 months corrected
age.
AB - Parenting stress has been linked to child development issues in early preterm
infants, but less is known about its effects on development in infants born late
preterm. We examined relationships between parenting stress of 108 mothers and
108 fathers and development of late preterm infants born at 34 0/7 to 36 6/7
weeks gestation. At 4 months corrected age, mothers and fathers completed the
Parenting Stress Index (PSI-3); mothers were primary caregivers in almost all
families and completed the Ages and Stages Questionnaire (ASQ-2) on child
development. Mothers reported significantly more stress than fathers on the PSI-3
Parent Domain. PSI-3 subscale scores from the Child Domain were significant
predictors of mother-reported infant development as measured by the ASQ-2 in
regression models: Reinforces Parent predicted Gross Motor, Mood predicted
Communication, and Acceptability predicted Communication, Fine Motor, Problem
Solving, and Personal -Social development scale scores. Experiences of parenting
stress differed for mothers and fathers. Further research is required on specific
dimensions of parenting stress related to development of late preterm infants.
PMID- 28704576
TI - Psychosis: an autoimmune disease?
AB - Psychotic disorders are common and disabling. Overlaps in clinical course in
addition to epidemiological and genetic associations raise the possibility that
autoimmune mechanisms may underlie some psychoses, potentially offering novel
therapeutic approaches. Several immune loci including the major
histocompatibility complex and B-cell markers CD19 and CD20 achieve genome-wide
significance in schizophrenia. Emerging evidence suggests a potential role via
neurodevelopment in addition to classical immune pathways. Additionally,
lymphocyte biology is increasingly investigated. Some reports note raised
peripheral CD19+ and reduced CD3+ lymphocyte counts, with altered CD4 : CD8
ratios in acute psychosis. Also, post-mortem studies have found CD3+ and CD20+
lymphocyte infiltration in brain regions that are of functional relevance to
psychosis. More specifically, the recent paradigm of neuronal surface antibody
mediated (NSAb) central nervous system disease provides an antigen-specific model
linking adaptive autoimmunity to psychopathology. NSAbs bind extracellular
epitopes of signalling molecules that are classically implicated in psychosis
such as NMDA and GABA receptors. This interaction may cause circuit dysfunction
leading to psychosis among other neurological features in patients with
autoimmune encephalitis. The detection of these cases is crucial as autoimmune
encephalitis is ameliorated by commonly available immunotherapies. Meanwhile, the
prevalence and relevance of these antibodies in people with isolated psychotic
disorders is an area of emerging scientific and clinical interest. Collaborative
efforts to achieve larger sample sizes, comparison of assay platforms, and
placebo-controlled randomized clinical trials are now needed to establish an
autoimmune contribution to psychosis.
PMID- 28704578
TI - Large-Diameter TiO2 Nanotubes Enable Wall Engineering with Conformal Hierarchical
Decoration and Blocking Layers for Enhanced Efficiency in Dye-Sensitized Solar
Cells (DSSC).
AB - Herein, we grew anodic TiO2 nanotube layer with a tube diameter >500 nm and an
open tube mouth. We use this morphology in dye-sensitized solar cells (DSSCs) and
show that these tubes allow the construction of hybrid hierarchical photoanode
structures of nanotubes with a defined and wall-conformal TiO2 nanoparticle
decoration. At the same time, the large diameter allows the successful
establishment of an additional (insulating) blocking layer of SiO2 or Al2 O3 on
the tube wall. We showed that this combination of hierarchical structure and
blocking layer significantly enhances the solar-cell efficiency by suppressing
recombination reactions. In such a DSSC structure, the solar-cell efficiency
under back side illumination with AM1.5 illumination was enhanced from 3 % for
the neat tube to 5 % for the hierarchical structure to 7 % when additionally a
blocking layer was attached.
PMID- 28704579
TI - Rhodium-Catalyzed Enantioselective Reductive Arylation: Convenient Access to 3,3
Disubstituted Oxindoles.
AB - A rhodium-Josiphos(L*) catalyzed enantioselective intramolecular hydroarylation
reaction is described. The reductive cyclization of o-bromoaniline-derived
acrylamides provides convenient access to 3,3-disubstituted oxindoles in good
yields and with excellent enantioselectivity across a range of substrates. We
propose that the key cyclization proceeds via a rhodium(III) intermediate.
Overall, this method represents an unusual mode of reactivity for rhodium
catalysis and is complementary to palladium(0)-catalyzed alpha-arylation methods.
PMID- 28704580
TI - Efficient discovery and capture of new neuronal nitric oxide synthase
postsynaptic density protein-95 uncouplers from herbal medicines using magnetic
molecularly imprinted polymers as artificial antibodies.
AB - In the scope of stroke treatment, new neuronal nitric oxide synthase-postsynaptic
density protein-95 uncouplers from herbal medicines were discovered and captured.
To do so, highly selective magnetic molecularly imprinted polymers with a core
shell structure were prepared as artificial antibodies. According to the results
of computational simulations, we designed and synthesized various polymers with
varying amounts and types of template, functional monomer, cross-linker, and
solvent. Characterization and performance tests revealed that the most
appropriate artificial antibodies showed uniform spherical morphologies, large
adsorption capacities, fast-binding kinetics, high selectivity, and quick
separation. These artificial antibodies were then used as sorbents for dispersive
magnetic solid-phase extraction coupled with high-performance liquid
chromatography and mass spectrometry to capture and identify structural analogs
to ZL006 from extracts of Scutellariae radix, Psoraleae fructus, and Trifolium
pratense. Furthermore, according to the neuroprotective effect and
coimmunoprecipitation test, Baicalein, Neobavaisoflavone, Corylifol A, and
Biochanin A can be the potential uncouplers of neuronal nitric oxide synthase
postsynaptic density protein-95. Therefore, this present study contributes
valuable information for the discovery of neuronal nitric oxide synthase
postsynaptic density protein-95 uncouplers from herbal medicines.
PMID- 28704581
TI - From Childhood to Adulthood: Disease Activity Trajectories in Childhood-Onset
Systemic Lupus Erythematosus.
AB - OBJECTIVE: No previous study has studied the longitudinal disease course of
childhood-onset systemic lupus erythematosus (cSLE). Our objectives are to assess
distinguishable differences in disease activity trajectories in cSLE patients,
determine baseline factors predictive of disease trajectory membership, and
assess if the different disease activity trajectories are associated with
different damage trajectories. METHODS: This is a retrospective, longitudinal
inception cohort of cSLE patients. Patients were followed from diagnosis as
children, until they were adults. SLE disease activity was modeled as a latent
characteristic, jointly using the Systemic Lupus Erythematosus Disease Activity
Index 2000 and prednisone in a Bayesian growth mixture model. Baseline factors
were tested for membership prediction of the latent classes of disease
trajectories. Differences in damage trajectories by disease activity classes were
tested using a mixed model. RESULTS: A total of 473 patients (82% females), with
median age at diagnosis of 14.1 years, were studied. We studied 11,992 visits
(2,666 patient-years). We identified 5 classes of disease activity trajectories.
Baseline major organ involvement, number of American College of Rheumatology
criteria, and age at diagnosis predicted memberships into different classes. A
higher proportion of Asians was in class 2 compared to class 5. Class 1 was
associated with the most accrual of damage, while class 5 was associated with no
significant damage accrual, even after 10 years. CONCLUSION: There are 5 distinct
latent classes of disease trajectory in patients with cSLE. Membership within
disease trajectories is predicted by baseline clinical and demographic factors.
Membership in different disease activity trajectory classes is associated with
different damage trajectories.
PMID- 28704582
TI - Autosomal dominant form of type IV collagen nephropathy exists among patients
with hereditary nephritis difficult to diagnose clinicopathologically.
AB - AIM: Type IV collagen nephropathies include Alport Syndrome and thin basement
membrane nephropathy (TBMN), which are caused by mutations in COL4A3/A4/A5 genes.
Recently, reports of patients with heterozygous mutations in COL4A3/A4 have been
increasing. The clinical course of these patients has a wide variety, and they
are diagnosed as TBMN, autosomal dominant Alport syndrome (ADAS), or familial
focal segmental glomerular sclerosis. However, diagnosis, frequency and
clinicopathological manifestation of them remains unclear. We tested COL4A3/A4/A5
genes in patients with hereditary nephritis that was difficult to diagnose
clinicopathologically, and investigated who should undergo such testing. METHODS:
We performed immunostaining for alpha5 chain of type IV collagen [alpha5 (IV)] in
27 patients from 21 families who fitted the following criteria: (i) haematuria
and proteinuria (+/- renal dysfunction); (ii) family history of haematuria,
proteinuria, and/or renal dysfunction (autosomal dominant inheritance); (iii) no
specific glomerulonephritis; and (iv) thinning, splitting, or lamellation of the
glomerular basement membrane (GBM) on electron microscopy. Then we performed
genetic testing in 19 patients from 16 families who showed normal alpha5 (IV)
patterns. We conducted a retrospective analysis of their clinicopathological
findings. RESULTS: Among 16 families, 69% were detected heterozygous mutations in
COL4A3/A4, suggesting the diagnosis of TBMN/ADAS. Twenty-one percent of patients
developed end stage renal disease. All patients showed thinning of GBM, which was
accompanied by splitting or lamellation in seven patients. CONCLUSION: A
considerable fraction of patients with hereditary nephritis that is difficult to
diagnose clinicopathologically have TBMN/ADAS. It is important to recognize
TBMN/ADAS and perform genetic testing in appropriate patients.
PMID- 28704583
TI - MnCl2 -Catalyzed C-H Alkylations with Alkyl Halides.
AB - C-H alkylations with challenging beta-hydrogen-containing alkyl halides were
accomplished with sustainable MnCl2 as the catalyst under phosphine-ligand-free
conditions. The proximity-induced benzamide C-H activation occurred with ample
substrate scope through rate-determining C-H metalation, also setting the stage
for manganese-catalyzed oxidative C-H methylations.
PMID- 28704584
TI - Patient-reported outcomes from SYNERGY, a randomized, double-blind, multicenter
study evaluating combinations of mirabegron and solifenacin compared with
monotherapy and placebo in OAB patients.
AB - AIMS: To evaluate patient-reported outcomes (PROs) of combinations of solifenacin
and mirabegron compared with solifenacin and mirabegron monotherapy and with
placebo in patients with overactive bladder (OAB) from the SYNERGY trial.
METHODS: Following a 4-week placebo run-in, period patients (>=18 years) with OAB
were randomized 2:2:1:1:1:1 to receive solifenacin 5 mg + mirabegron 25 mg
(combination 5 + 25 mg), solifenacin 5 mg + mirabegron 50 mg, (combination 5 + 50
mg), solifenacin 5 mg, mirabegron 25 mg, mirabegron 50 mg or placebo for 12
weeks, followed by a 2-week washout period. At each visit, PROs related to
quality of life, symptom bother, and treatment satisfaction were assessed,
including OAB-q Symptom Bother score, health-related quality of life (HRQOL)
Total score, treatment satisfaction-visual analogue scale (TS-VAS), and patient
perception of bladder condition (PPBC) questionnaires. RESULTS: Overall, 3527
patients were randomized into the study, with 3494 receiving double-blind
treatment. At end of treatment (EoT), both combination groups showed greater
improvements in OAB-q Symptom Bother score compared with the monotherapy groups
(nominal P < 0.001). Statistically significant improvements in HRQOL Total scores
were observed in the combination groups versus monotherapy groups (P <= 0.002).
For both combination groups, the OAB-q Symptom Bother score responder rates at
EoT were statistically significantly higher versus mirabegron monotherapy (P <
0.05). The mean adjusted changes from baseline to EoT for PPBC were greater in
the combination groups compared with monotherapy groups. CONCLUSIONS: PROs showed
that combination therapy provided clear improvements and an additive effect for
many HRQOL parameters, including OAB-q Symptom Bother score, HRQOL Total score,
and PPBC.
PMID- 28704586
TI - Assessment of Density Functionals for Computing Thermodynamic Properties of
Lanthanide Complexes.
AB - The equilibrium between the radical phenanthroline complex Cp*2 Sm(phen) and the
coupling product (Cp*2 Sm(phen))2 has been investigated based on quantum
chemistry calculations. Topological analyses pointed out that the C-C bond
created has a partial covalent character, explaining why both the monomeric and
the dimeric forms exist in equilibrium. A large variety of density functionals
have been tested to reproduce experimental thermodynamic data for this
equilibrium. Finally, the PBE0-D3 and M06-2X functionals lead to a good
evaluation of the energies and enable a correct description of the ligand to
metal charge transfer, both in the 4f and 5d metal orbitals.
PMID- 28704585
TI - Structure of the adenylation domain Thr1 involved in the biosynthesis of 4
chlorothreonine in Streptomyces sp. OH-5093-protein flexibility and molecular
bases of substrate specificity.
AB - : We determined the crystal structure of Thr1, the self-standing adenylation
domain involved in the nonribosomal-like biosynthesis of free 4-chlorothreonine
in Streptomyces sp. OH-5093. Thr1 shows two monomers in the crystallographic
asymmetric unit with different relative orientations of the C- and N-terminal
subdomains both in the presence of substrates and in the unliganded form.
Cocrystallization with substrates, adenosine 5'-triphosphate and l-threonine,
yielded one monomer containing the two substrates and the other in complex with l
threonine adenylate, locked in a postadenylation state. Steady-state kinetics
showed that Thr1 activates l-Thr and its stereoisomers, as well as d-Ala, l- and
d-Ser, albeit with lower efficiency. Modeling of these substrates in the active
site highlighted the molecular bases of substrate discrimination. This work
provides the first crystal structure of a threonine-activating adenylation
enzyme, a contribution to the studies on conformational rearrangement in
adenylation domains and on substrate recognition in nonribosomal biosynthesis.
DATABASE: Structural data are available in the Protein Data Bank under the
accession number 5N9W and 5N9X.
PMID- 28704587
TI - Effects of testosterone administration (and its 5-alpha-reduction) on parenchymal
organ volumes in healthy young men: findings from a dose-response trial.
AB - Animal data shows that testosterone administration increases the volume of some
parenchymal organs. However, the effects of exogenous testosterone on solid
abdominal organs in humans remain unknown. The present study evaluated the
effects of testosterone administration on the volume of liver, spleen and kidneys
in a dose-response trial. Young healthy men aged 18-50 years participating in the
5alpha-Reductase (5aR) Trial. All participants received monthly injections of 7.5
mg leuprolide acetate to suppress endogenous testosterone secretion and weekly
injections of 50, 125, 300 or 600 mg of testosterone enanthate, and were
randomized to receive either 2.5 mg dutasteride (5 alpha-reductase inhibitor) or
placebo daily for 20 weeks. Liver, spleen and kidney volumes were measured at
baseline and the end of treatment using 1.5-Tesla magnetic resonance imaging. The
dose-effect of testosterone on changes in the volume of parenchymal organs was
evaluated by linear regression model. The association between changes in total
testosterone (TT) levels and changes in organ volumes were assessed. Testosterone
administration increased liver volume dose-dependently (17.4 cm3 per 100 mg of
weekly testosterone enanthate; p = 0.031); the increase in liver volume was
positively associated with changes in TT levels (R2 = 0.08, p = 0.024). A dose
dependent, but non-significant, increase in kidney volumes was also seen.
Inclusion of dutasteride use into the models showed an independent association of
randomization to dutasteride group with liver volume increase. In conclusion,
Testosterone administration increased the liver volume in a dose-dependent
manner. The potential changes in parenchymal organs should be considered when
interpreting apparent changes in lean mass in response to anabolic interventions.
PMID- 28704588
TI - Here, there and everywhere: T follicular helper cells on the move.
AB - T follicular helper (Tfh) cells have the important function of providing B-cell
help for the induction of antigen-specific antibody production. As such, it is
important to determine the factors that regulate the development, differentiation
and function of Tfh cells. This review highlights some of the recent advances in
our understanding of Tfh cell migration, Tfh cell memory and the origins and fate
of circulating Tfh cells in the blood, that have been revealed from studies in
humans and mice.
PMID- 28704589
TI - Novel chemiluminescent Western blot blocking and antibody incubation solution for
enhanced antibody-antigen interaction and increased specificity.
AB - Western blotting is a ubiquitous tool used in protein and molecular biology
research, providing information about the presence, size, relative abundance, and
state of a protein in a mixture. First, the proteins in a sample are separated by
size using SDS-PAGE then transferred onto a membrane for detection with a set of
primary and secondary antibodies. High-quality Western data requires high signal
to-noise ratios, which depend upon reduction of nonspecific antibody
interactions. Blocking is a critical step in the Western blot method as it
prevents the antibodies from binding nonspecifically to the membrane and
irrelevant proteins. A solution of nonfat dry milk (NFDM) in physiological buffer
is commonly used for this purpose, but does not perform well with every type of
antibody and is not optimal for low-abundance proteins. We present a novel
blocking solution for chemiluminescent Western blots, AdvanBlockTM-chemi, which
outperforms NFDM in experiments with 20 unique antibodies by increasing signal-to
noise ratios and minimizing nonspecific binding. This solution enhances protein
detection by Western blot and provides consistent results for detection of low
abundant and modified proteins.
PMID- 28704590
TI - The influence of democratic racism in nursing inquiry.
AB - Neoliberal ideology and exclusionary policies based on racialized identities
characterize the current contexts in North America and Western Europe. Nursing
knowledge cannot be abstracted from social, political and historical contexts;
the task of examining the influence of race and racial ideologies on disciplinary
knowledge and inquiry therefore remains an important task. Contemporary analyses
of the role and responsibility of the discipline in addressing race-based health
and social inequities as a focus of nursing inquiry remain underdeveloped. In
this article, we examine nursing's engagement with ideas about race and racism
and explore the ways in which nursing knowledge and inquiry have been influenced
by race-based ideological discourses. Drawing on Henry and Tator's framework of
democratic racism, we consider how strategic discursive responses-the discourses
of individualism, multiculturalism, colour-blindness, political correctness and
denial-have been deployed within nursing knowledge and inquiry to reinforce the
belief in an essentially fair and just society while avoiding the need to
acknowledge the persistence of racist discourses and ideologies. Greater
theoretical, conceptual and methodological clarity regarding race, racialization
and related concepts in nursing inquiry is needed to address health and social
inequities.
PMID- 28704591
TI - Erratum: A Nanoscaffold Impregnated With Human Wharton's Jelly Stem Cells or Its
Secretions Improves Healing of Wounds.
PMID- 28704592
TI - Erratum: Human Wharton's Jelly Stem Cells and Its Conditioned Medium Enhance
Healing of Excisional and Diabetic Wounds.
PMID- 28704594
TI - Critical diagnoses in cytopathology: Experience at a large medical center.
AB - BACKGROUND: Critical values have been well established and accepted in laboratory
medicine, but to the authors' knowledge are less well accepted in anatomic
pathology. Herein, the authors used a reporting process whereby reports with
critical diagnoses were coded to ensure that the patient's clinical team was
promptly notified electronically of this finding. The aim of the current study
was to determine whether this coding mechanism was used appropriately for
critical cytopathology diagnoses in the study health care system. METHODS: A
retrospective review of the University of Pittsburgh Medical Center anatomic
pathology laboratory information system was performed to identify cytopathology
reports in which a critical diagnosis code (MedTrak notification/CoPath Tissue
Code TC66; TC66) was used from 2011 through 2016. TC66-coded cytopathology
reports between 2015 and 2016 were reviewed further to determine whether this
code was used appropriately. RESULTS: A total of 1687 TC66-coded cytopathology
reports were identified. Between 2015 and 2016, a total of 30 of 46 reports (65%)
from academic hospitals and 46 of 441 reports (10%) from community hospitals met
the critical diagnoses criteria outlined by institutional policy. The remaining
TC66-coded cases were predominantly for new diagnoses of malignancy in patients
clinically suspected of having cancer. CONCLUSIONS: Use of a code for critical
cytopathology diagnoses was found to be occurring increasingly at the study
health care system. Pathologists at the academic and community hospitals in the
study institution used this code somewhat differently, reflecting the need to
satisfy communication with clinicians in different practice settings.
Nevertheless, the authors' experiences with using a code for critical diagnoses
not only ensured timely patient care but also proposed a model that could be used
by other medical specialties to enhance communication and improve quality of
care. Cancer Cytopathol 2017;125:726-30. (c) 2017 American Cancer Society.
PMID- 28704595
TI - Results of implementation of a hospital-based strategy to reduce cesarean
delivery among low-risk women in Canada.
AB - OBJECTIVE: To assess the cesarean delivery (CD) rate among low-risk pregnancies
before and after implementation of a hospital-based program in Canada. METHODS: A
prospective before-and-after study was conducted to assess the effects of the
CARE (CAesarean REduction) strategy, which was developed and implemented at
Markham Stouffville Hospital, Toronto, ON, Canada, in 2010 to reduce CD among low
risk women. Hospital records were reviewed to identify changes in the proportions
of CD performed during 12 months (April 2009-March 2010) before implementation of
the CARE strategy versus 12 months after implementation (April 2012-March 2013)
at Markham Stouffville Hospital and 36 hospitals of the same level in the same
province. RESULTS: At the intervention hospital, 30.3% (964/3181) of women
underwent CD in 2009-2010, compared with 26.4% (803/3045) in 2012-2013
(difference -3.9%, P<0.001). By contrast, no significant difference was recorded
in control hospitals (28.1% [23 694/84 361] vs 28.2% [23 683/83 895]; difference
0.1%, P=0.5157). CONCLUSION: Implementation of the CARE strategy reduced rates of
CD among the target population.
PMID- 28704596
TI - Silver nanoparticles functionalized with ampicillin.
AB - The resistance of pathogenic bacteria to antibiotics has become a serious
problem. The emphasis is placed on the development of new, effective
antimicrobial strategies. One of them is the use of AgNPs in association with
antibiotic drugs. The aim of this study was to obtain silver nanoparticles
functionalized with ampicillin and to investigate the mechanism of binding
antibiotics to nanoparticle using high-performance liquid chromatography
approach. To confirm the occurrence of silver nanoparticles functionalization,
FTIR, MALDI-TOF MS, and DLS analysis and zeta potential measurements were
performed. Moreover we assessed the antibacterial activity of biologically
synthesized nanoparticles functionalized with ampicillin against a range of gram
(+) and gram (-) bacteria strains such as Staphylococcus aureus, Pseudomonas
aeruginosa, Klebsiella pneumoniae, Staphylococcus epidermidis, and Escherichia
coli.
PMID- 28704597
TI - Are incident gallstones associated to sex-dependent changes with age? A cohort
study.
AB - Age and female sex have repeatedly been identified as gallstone determinants but
the underlying mechanisms are not clarified. The objectives of this study were to
determine if changes with age in physiology, lifestyle, or reproductive hormones
were associated with incident gallstones. A cohort study of a general population
random sample (N = 2366) aged 30-60 years was performed. Participants were
ultrasound screened for gallstones in 1982-84 and again in 1993-94. Lifestyle
data and blood samples were obtained and re-analyzed in 2004. Changes with age in
physiology (body mass index, blood pressure, blood lipids, self-rated health),
lifestyle (smoking, alcohol and coffee consumption, dietary habits, physical
activity level), and indices of reproductive function (number of births, oral
contraceptive use, hormone replacement therapy, male reproductive hormones) were
explored in females and males separately. Adjusted logistic regression analyses
were performed. Incident gallstones (gallstones and cholecystectomy) at
ultrasound examination in participants initially free of gallstones at baseline
occurred in 9.9% of the study population. In females, increasing alcohol
consumption (odds ratio (OR) 0.94, 95% confidence interval (CI) [0.90; 0.98]) and
the cessation of hormone replacement therapy (OR 0.29, 95% CI [0.10; 0.83])
inversely determined incident gallstones. In males, increasing levels of SHBG (OR
0.97, 95% CI [0.94; 0.998]) inversely determined incident gallstones. Other
changes with age in physiology, lifestyle, or reproductive hormones were not
associated. High baseline free testosterone determined incident gallstones in
males (OR 1.15, 95% CI [1.02; 1.30]). To conclude, changes with age in alcohol
consumption in females and in reproductive hormones determined incident
gallstones. Male reproductive hormones seem to have an impact on incident
gallstones. Sex differences should be explored further in future studies.
PMID- 28704598
TI - Restrictive Use of Oral Glucocorticoids in Systemic Lupus Erythematosus and
Prevention of Damage Without Worsening Long-Term Disease Control: An
Observational Study.
AB - OBJECTIVE: To analyze the influence of 2 different treatment strategies on
general and specific damage accrual in patients with systemic lupus erythematosus
(SLE). METHODS: Two cohorts were identified according to the responsible
physicians: patients treated at the autoimmune diseases unit (ADU), and patients
treated by other members of the internal medicine (IM) department. Members of the
ADU worked with a protocol including the universal prescription of
hydroxychloroquine (HCQ), the use of maximum oral prednisone dosages <=30 mg/day
and maintenance therapy with <=5 mg/day, by using methylprednisolone pulses
and/or early immunosuppressive (IS) drugs. We analyzed the influence of these 2
treatment strategies on damage accrual, both general and domain specific,
attributed to glucocorticoids, cardiovascular (CV) disease, SLE, and
unclassified, since the diagnosis of disease in patients with a followup >=5
years. RESULTS: A total of 74 patients were included in the ADU group and 213 in
the IM group. They were comparable for most demographic and lupus-related
variables. ADU patients received prednisone later and at lower doses, more
methylprednisolone pulses, earlier IS drugs and more HCQ (P < 0.05 for all
comparisons). The Systemic Lupus Erythematosus Disease Activity Index score
decreased similarly in both cohorts (P = 0.4). Patients in the ADU group were
less likely to accrue any damage (P = 0.007). They accrued less glucocorticoid
related (adjusted hazard ratio [HR] 0.23 [95% confidence interval (95% CI) 0.07
0.80]), CV disease (adjusted HR 0.28 [95% CI 0.08-0.95]), and unclassified damage
(adjusted HR 0.58 [95% CI 0.3-1.1]). Both groups accrued similar SLE-related
damage (adjusted HR 0.84 [95% CI 0.40-1.75]). CONCLUSION: The use of reduced oral
prednisone doses, which was possible by combining different therapies, reduced
glucocorticoid-related damage and improved CV prognosis without increasing damage
caused by SLE.
PMID- 28704599
TI - Association of Anti-Transcription Intermediary Factor 1gamma Antibodies With
Paraneoplastic Rheumatic Syndromes Other Than Dermatomyositis.
AB - OBJECTIVE: An association between cancer and dermatomyositis (DM) is well
recognized. The high frequency of malignancies detected close to DM diagnosis
suggest that DM can be a paraneoplastic syndrome. Recently, anti-transcription
intermediary factor 1gamma (anti-TIF1gamma) has been discovered to be associated
with cancer and with DM. A meta-analysis reported the pooled sensitivity of anti
p155 for diagnosing cancer-associated DM to be 78% and the specificity to be 89%.
Thus, anti-TIF1gamma has shown promising results as a marker for cancer
associated DM. However, none of the studies evaluated the association of anti
TIF1gamma with cancer with or without rheumatic diseases other than DM. To
clarify the specificity of anti-TIF1gamma antibodies as a biomarker for cancer
associated DM, we analyzed the frequency of anti-TIF1gamma antibodies in other
cancer-associated rheumatic syndromes, as well as in cancer patients and healthy
controls. METHODS: Sera from patients with paraneoplastic rheumatic syndrome (n =
91), patients with solid cancer (n = 95), and healthy controls (n = 80) were
analyzed for the frequency of anti-TIF1gamma IgG by enzyme-linked immunosorbent
assay using a commercially available recombinant TIF1gamma protein as coating
antigen. The cutoff value was calculated by adding 2 SD to the mean optical
density value of 80 healthy controls. RESULTS: The rate of anti-TIF1gamma IgG
positivity was 3.3% (n = 3) in patients with paraneoplastic rheumatic syndrome,
3.1% (n = 3) in cancer patients, and 1.3% (n = 1) in healthy controls. There were
no significant differences in positivity between the groups (P < 0.05).
CONCLUSION: Anti-TIF1gamma antibodies are rarely present in patients with solid
cancers or paraneoplastic rheumatic syndromes. This finding strengthens the
approach to using anti-TIF1gamma IgG as a marker for cancer-associated DM.
PMID- 28704600
TI - Comparable Rates of Glucocorticoid-Associated Adverse Events in Patients With
Polymyalgia Rheumatica and Comorbidities in the General Population.
AB - OBJECTIVE: To investigate the use of glucocorticoids (GCs) and related adverse
events (AEs) in a long-term, geographically defined cohort of patients with
polymyalgia rheumatica (PMR). METHODS: Using a population-based inception cohort,
details of GC therapy were abstracted from medical records of all patients
diagnosed with PMR in 2000-2014. Age- and sex-matched comparators without PMR
were identified from the same underlying population. Cumulative and daily dosage
of GC, rate of disease relapse, occurrence of GC-related AEs, and rate of GC
discontinuation were analyzed. RESULTS: The study included 359 patients with PMR
and 359 comparators. The median time to taper below 5 mg/day for 6 months was
1.44 years (95% confidence interval [95% CI] 1.36-1.62), while the median time to
permanent discontinuation was 5.95 years (95% CI 3.37-8.88). The mean +/- SD
cumulative dose of GC at 2 and 5 years was 4.0 +/- 3.5 grams and 6.3 +/- 9.8
grams, respectively. The mean +/- SD daily dose of GC at 2 and 5 years was 6.1 +/
7.6 mg/day and 7.2 +/- 9.5 mg/day, respectively. There were no differences in
rates of AEs between patients with PMR and comparators for diabetes mellitus,
hypertension, hyperlipidemia, or hip, vertebral, or Colles fractures (P > 0.2 for
all). Cataracts were more common in patients with PMR than comparators (hazard
ratio 1.72 [95% CI 1.23-2.41]). CONCLUSION: Relapse rates in PMR are highest in
the early stages of therapy. Despite often protracted therapy, with the exception
of cataracts, the rates of studied morbidities linked to GC are not more common
in PMR than comparators.
PMID- 28704601
TI - Reply.
PMID- 28704602
TI - Defective Early B Cell Tolerance Checkpoints in Sjogren's Syndrome Patients.
AB - OBJECTIVE: Central and peripheral B cell tolerance checkpoints are defective in
many patients with autoimmune diseases, but the functionality of each discrete
checkpoint has not been assessed in patients with Sjogren's syndrome (SS). We
undertook this study to assess this functionality in SS patients. METHODS: Using
a polymerase chain reaction-based approach that allows us to clone and express,
in vitro, recombinant antibodies produced by single B cells, we tested the
reactivity of recombinant antibodies cloned from single CD19+CD21low CD10+IgMhigh
CD27- newly emigrant/transitional B cells and CD19+CD21+CD10-IgM+CD27- mature
naive B cells from 5 SS patients. RESULTS: We found that the frequencies of newly
emigrant/transitional B cells expressing polyreactive antibodies were
significantly increased in SS patients compared to those in healthy donors,
revealing defective central B cell tolerance in SS patients. Frequencies of
mature naive B cells expressing autoreactive antibodies were also significantly
increased in SS patients, thereby illustrating an impaired peripheral B cell
tolerance checkpoint in these patients. CONCLUSION: Defective counterselection of
developing autoreactive B cells observed in SS patients is a feature common to
many other autoimmune diseases and may favor the development of autoimmunity by
allowing autoreactive B cells to present self antigens to T cells.
PMID- 28704603
TI - Relationship Between Knee Pain and Infrapatellar Fat Pad Morphology: A Within-
and Between-Person Analysis From the Osteoarthritis Initiative.
AB - OBJECTIVE: Inflammation is known to be strongly associated with knee pain in
osteoarthritis. The infrapatellar fat pad represents a potential source of
proinflammatory cytokines. Yet the relationship between infrapatellar fat pad
morphology and osteoarthritis symptoms is unclear. METHODS: Here we investigate
quantitative imaging parameters of infrapatellar fat pad morphology between
painful versus contralateral pain-free legs of subjects with unilateral knee pain
and patients with chronic knee pain versus those of matched pain-free control
subjects. A total of 46 subjects with strictly unilateral frequent knee pain and
bilateral radiographic osteoarthritis (Kellgren/Lawrence grade 2/3) were drawn
from the Osteoarthritis Initiative. Further, 43 subjects with chronic knee pain
over 4 years and 43 matched pain-free controls without pain over this period were
studied. Infrapatellar fat pad morphology (volume, surface area, and depth) was
determined by manual segmentation of sagittal magnetic resonance images. RESULTS:
No significant differences in infrapatellar fat pad morphology were observed
between painful versus painless knees of persons with strictly unilateral knee
pain (mean difference -0.7% (95% confidence interval [95% CI] -0.6, 0.9; P =
0.64) or between chronically painful knees versus matched painless controls (
2.1% [95% CI -2.2, 1.1]; P = 0.51). CONCLUSION: Independent of the ambiguous role
of the infrapatellar fat pad in knee osteoarthritis (a potential source of
proinflammatory cytokines or a mechanical shock absorber), the size of the
infrapatellar fat pad does not appear to be related to knee pain.
PMID- 28704604
TI - Methodologic Questions Regarding Study of the Efficacy of Chondroitin
Sulfate/Glucosamine Treatment of Knee Osteoarthritis: Comment on the Article by
Roman-Blas et al.
PMID- 28704605
TI - Protein Adsorption to Charged Gold Nanospheres as a Function of Protein
Deformability.
AB - The corona that forms as protein adsorbs to gold nanospheres (AuNSs) is directly
influenced by the surface chemistry of the AuNS. Tools to predict adsorption
outcomes are needed for intelligent design of nanomaterials for biological
applications. We hypothesized that the denaturation behavior of a protein might
be a useful predictor of adsorption behavior to AuNSs, and used this idea to
study protein adsorption to anionic citrate-capped AuNSs and to cationic
poly(allylamine hydrochloride) (PAH) wrapped AuNSs. Three proteins (alpha-amylase
(A-Amy), beta-lactoglobulin (BLG), and bovine serum albumin (BSA)), representing
three different classes of acid denaturation behavior, were selected with BLG
being the least deformable and BSA being the most deformable. Protein adsorption
to AuNSs was monitored via UV-vis spectrophotometry and dynamic light scattering.
Changes to the protein structure upon AuNS interaction were monitored via
circular dichroism spectroscopy. Binding constants were determined using the
Langmuir adsorption isotherm, resulting in BSA > BLG ? A-Amy affinities for
citrate-capped gold nanospheres. PAH-coated AuNSs displayed little affinity for
these proteins at similar concentrations as citrate-coated AuNSs and became
agglomerated at high protein concentrations. The enzymatic activity of A
Amy/citrate AuNS conjugates was measured via colorimetric assay, and found to be
11% of free A-Amy, suggesting that binding restricts access to the active site.
Across both citrate AuNSs and PAH AuNSs, the changes in secondary structure were
greatest for BSA > A-Amy > BLG, which does follow the trends predicted by acid
denaturation characteristics.
PMID- 28704606
TI - Metallic Conductivity in a Two-Dimensional Cobalt Dithiolene Metal-Organic
Framework.
AB - Two-dimensional (2D) metal-organic frameworks (MOFs) have received a great deal
of attention due to their relatively high charge carrier mobility and low
resistivity. Here we report on the temperature-dependent charge transport
properties of a 2D cobalt 2,3,6,7,10,11-triphenylenehexathiolate framework.
Variable temperature resistivity studies reveal a transition from a
semiconducting to a metallic phase with decreasing temperature, which is
unprecedented in MOFs. We find this transition to be highly dependent on the film
thickness and the amount of solvent trapped in the pores, with density functional
theory calculations of the electronic-structure supporting the complex metallic
conductivity of the material. These results identify the first experimentally
observed MOF that exhibits band-like metallic conductivity.
PMID- 28704607
TI - Highly Efficient Oxygen Reduction Reaction Electrocatalysts Synthesized under
Nanospace Confinement of Metal-Organic Framework.
AB - The output energy capacity of green electrochemical devices, e.g., fuel cells,
depends strongly on the sluggish oxygen reduction reaction (ORR), which requires
catalysts. One of the desired features for highly efficient ORR electrocatalytic
materials is the richness of well-defined activate sites. Herein, we developed a
facile approach to prepare highly efficient nonprecious metal and nitrogen-doped
carbon-based ORR catalysts based on covalent organic polymers (COPs) synthesized
in situ in the nanoconfined space of highly ordered metal organic frameworks
(MOFs). The MOF templet ensured the developed electrocatalysts possess a high
surface area with homogeneously distributed small metal/nitrogen active sites, as
confirmed by X-ray absorption fine structure measurements and first-principles
calculations, leading to highly efficient ORR electrocatalytic activity. Notably,
the developed COP-TPP(Fe)@MOF-900 exhibits a 16 mV positive half-wave potential
compared with the benchmarked Pt/C.
PMID- 28704608
TI - The Electron Bifurcating FixABCX Protein Complex from Azotobacter vinelandii:
Generation of Low-Potential Reducing Equivalents for Nitrogenase Catalysis.
AB - The biological reduction of dinitrogen (N2) to ammonia (NH3) by nitrogenase is an
energetically demanding reaction that requires low-potential electrons and ATP;
however, pathways used to deliver the electrons from central metabolism to the
reductants of nitrogenase, ferredoxin or flavodoxin, remain unknown for many
diazotrophic microbes. The FixABCX protein complex has been proposed to reduce
flavodoxin or ferredoxin using NADH as the electron donor in a process known as
electron bifurcation. Herein, the FixABCX complex from Azotobacter vinelandii was
purified and demonstrated to catalyze an electron bifurcation reaction: oxidation
of NADH (Em = -320 mV) coupled to reduction of flavodoxin semiquinone (Em = -460
mV) and reduction of coenzyme Q (Em = 10 mV). Knocking out fix genes rendered
Deltarnf A. vinelandii cells unable to fix dinitrogen, confirming that the
FixABCX system provides another route for delivery of electrons to nitrogenase.
Characterization of the purified FixABCX complex revealed the presence of flavin
and iron-sulfur cofactors confirmed by native mass spectrometry, electron
paramagnetic resonance spectroscopy, and transient absorption spectroscopy.
Transient absorption spectroscopy further established the presence of a short
lived flavin semiquinone radical, suggesting that a thermodynamically unstable
flavin semiquinone may participate as an intermediate in the transfer of an
electron to flavodoxin. A structural model of FixABCX, generated using chemical
cross-linking in conjunction with homology modeling, revealed plausible electron
transfer pathways to both high- and low-potential acceptors. Overall, this study
informs a mechanism for electron bifurcation, offering insight into a unique
method for delivery of low-potential electrons required for energy-intensive
biochemical conversions.
PMID- 28704609
TI - Hydrophilic and Cell-Penetrable Pyrrolidinyl Peptide Nucleic Acid via Post
synthetic Modification with Hydrophilic Side Chains.
AB - Peptide nucleic acid (PNA) is a nucleic acid mimic in which the deoxyribose
phosphate was replaced by a peptide-like backbone. The absence of negative charge
in the PNA backbone leads to several unique behaviors including a stronger
binding and salt independency of the PNA-DNA duplex stability. However, PNA
possesses poor aqueous solubility and cannot directly penetrate cell membranes.
These are major obstacles that limit in vivo applications of PNA. In previous
strategies, the PNA can be conjugated to macromolecular carriers or modified with
positively charged side chains such as guanidinium groups to improve the aqueous
solubility and cell permeability. In general, a preformed modified PNA monomer
was required. In this study, a new approach for post-synthetic modification of
PNA backbone with one or more hydrophilic groups was proposed. The PNA used in
this study was the conformationally constrained pyrrolidinyl PNA with prolyl-2
aminocyclopentanecarboxylic acid dipeptide backbone (acpcPNA) that shows several
advantages over the conventional PNA. The aldehyde modifiers carrying different
linkers (alkylene and oligo(ethylene glycol)) and end groups (-OH, -NH2, and
guanidinium) were synthesized and attached to the backbone of modified acpcPNA by
reductive alkylation. The hybrids between the modified acpcPNAs and DNA exhibited
comparable or superior thermal stability with base-pairing specificity similar to
those of unmodified acpcPNA. Moreover, the modified apcPNAs also showed the
improvement of aqueous solubility (10-20 folds compared to unmodified PNA) and
readily penetrate cell membranes without requiring any special delivery agents.
This study not only demonstrates the practicality of the proposed post-synthetic
modification approach for PNA modification, which could be readily applied to
other systems, but also opens up opportunities for using pyrrolidinyl PNA in
various applications such as intracellular RNA sensing, specific gene detection,
and antisense and antigene therapy.
PMID- 28704610
TI - Effects of Medium- and Long-Chain Triacylglycerols on Lipid Metabolism and Gut
Microbiota Composition in C57BL/6J Mice.
AB - Obesity is related to an increasing risk of chronic diseases. Medium- and long
chain triacylglycerols (MLCT) have been recognized as a promising choice to
reduce body weight. In this study, three MLCT with different contents of medium
chain fatty acids (MCFA) (10-30%, w/w) were prepared, and their effects on lipid
metabolism and fecal gut microbiota composition of C57BL/6J mice were
systematically investigated. MLCT with 30% (w/w) MCFA showed the best performance
in decreasing body weight gain as well as optimizing serum lipid parameters and
liver triacylglycerol content. The expression levels of genes encoding enzymes
for fatty acid degradation increased markedly and expression levels of genes
encoding enzymes for de novo fatty acid biosynthesis decreased significantly in
the liver of mice treated with MLCT containing 30% (w/w) MCFA. Interestingly, the
dietary intake of a high fat diet containing MLCT did significantly decrease the
ratio of Firmicutes to Bacteroidetes and down-regulate the relative abundance of
Proteobacteria that may attribute to weight loss. Furthermore, we found a notable
increase in the total short-chain fatty acid (SCFA) content in feces of mice on a
MLCT containing diet. All these results may be concomitantly responsible for the
antiobesity effect of MLCT with relatively high contents of MCFA.
PMID- 28704611
TI - Grasslands: A Source of Secondary Metabolites for Livestock Health.
AB - The need for environmentally friendly practices in animal husbandry, in
conjunction with the reduction of the use of synthetic chemicals, leads us to
reconsider our agricultural production systems. In that context, grassland
secondary metabolites (GSMs) could offer an alternative way to support to
livestock health. In fact, grasslands, especially those with high dicotyledonous
plant species, present a large, pharmacologically active reservoir of secondary
metabolites (e.g., phenolic compounds, alkaloids, saponins, terpenoids,
carotenoids, and quinones). These molecules have activities that could improve or
deteriorate health and production. This Review presents the main families of GSMs
and uses examples to describe their known impact on animal health in husbandry.
Techniques involved for their study are also described. A particular focus is put
on anti-oxidant activities of GSMs. In fact, numerous husbandry pathologies, such
as inflammation, are linked to oxidative stress and can be managed by a diet rich
in anti-oxidants. The different approaches and techniques used to evaluate
grassland quality for livestock health highlight the lack of efficient and
reliable technics to study the activities of this complex phytococktail. Better
knowledge and management of this animal health resource constitute a new
multidisciplinary research field and a challenge to maintain and valorize
grasslands.
PMID- 28704612
TI - Blood flow in humans following low-load exercise with and without blood flow
restriction.
AB - Blood flow restriction (BFR) in combination with exercise has been used to
increase muscle size and strength using relatively low loads (20%-30% 1
repetition maximum (1RM)). In research, the range of applied pressures based on a
percentage of arterial occlusion pressure (AOP), is wide. The purpose of the
study is to measure the blood flow response before exercise, following each set
of exercise, and postexercise to low-load elbow flexion combined with no
restriction (NOBFR), 40% of AOP (40BFR), and 80% of AOP (80BFR). One hundred and
fifty-two participants volunteered; 140 completed the protocol (women = 75, men =
65). Participants were counter-balanced into 1 of 3 conditions. Following AOP and
1RM measurement, ultrasound was used to measure standing blood flow at rest in
the right brachial artery. Participants performed 4 sets of elbow flexion at 30%
1RM. Blood flow was measured between sets and at 1 and 5 min postexercise. Blood
flow decreased following inflation, with no difference between conditions (p <
0.001). Men had greater blood flow than women in all conditions at all time
points (p < 0.001). Resting hyperemia decreased with pressure (NOBFR > 40BFR >
80BFR, p < 0.001). Blood flow increased from rest to after set 1 regardless of
condition. Following cuff deflation, blood flow increased in both the 80BFR and
40BFR conditions. The reduction in hyperemia during BFR is pressure-dependent.
Contrary to previous investigations, blood flow was increased above baseline
following exercise.
PMID- 28704613
TI - Antioxidant compound (E)-2-benzylidene-4-phenyl-1,3-diselenole protects rats
against thioacetamide-induced acute hepatotoxicity.
AB - The aim of this study was to investigate whether (E)-2-benzylidene-4-phenyl-1,3
diselenole (BPD) protects against hepatotoxicity induced by thioacetamide (TAA).
On the first day of treatment, male adult Wistar rats received BPD (10 or 50
mg.kg-1). On the second day, the rats received a single intraperitoneal injection
of TAA (400 mg.kg-1). Twenty-four hours after TAA administration, biochemical
determinations and liver histological analysis were carried out. BPD (50 mg.kg-1)
reduced plasma aspartate and alanine aminotransferase, alkaline phosphatase, and
lactate dehydrogenase activities increased by TAA exposure. Treatment with BPD
was effective against increased lipid peroxidation levels and attenuated a
decrease in hepatic reduced glutathione and ascorbic acid levels as well as an
inhibition of glutathione peroxidase activity caused by TAA exposure. The higher
dose of BPD protected against the inhibition of hepatic delta-aminolevulinic
dehydratase activity induced by TAA. Finally, histopathological examination of
the liver showed that BPD markedly ameliorated TAA-induced hepatic injury. In
conclusion, BPD protected against hepatotoxicity and oxidative stress caused by
TAA exposure in rats.
PMID- 28704614
TI - Carbon dioxide water-bath treatment augments peripheral blood flow through the
development of angiogenesis.
AB - In this study, we investigated the effects of CO2 water-bath therapy on blood
flow and angiogenesis in the ischemic hind limb, as well as some plasma
angiogenic factors in peripheral ischemic model. The hind limb ischemia was
induced by occluding the femoral artery for 2 weeks in rats and treated with or
without CO2 water-bath therapy at 37 degrees C for 4 weeks (20 min treatment
every day for 5 days per week). The peak blood flow and minimal and mean blood
flow in the ischemic skeletal muscle were markedly increased by the CO2 water
bath therapy. This increase in blood flow was associated with development of
angiogenesis in the muscle, as well as reduction in the ischemia-induced increase
in plasma malondialdehyde levels. Although plasma vascular endothelial growth
factor and nitric oxide levels were increased in animals with peripheral
ischemia, the changes in these biomarkers were not affected by CO2 water-bath
therapy. These results suggest that augmentation of blood flow in the ischemic
hind limb by CO2 water-bath therapy may be due to the development of angiogenesis
and reduction in oxidative stress.
PMID- 28704615
TI - Solitary Benign Schwannoma of the Foot Presenting Clinically as a Ganglion Cyst A
Case Study.
AB - An unusual case of solitary benign schwannoma of the foot is presented. Clinical
examination, magnetic resonance imaging, and intraoperative findings all confirm
the suspicion of a ganglion cyst. After attempted aspiration failed to produce
any aspirate, excisional biopsy was performed. The pathology report confirms
schwannoma with hematoxylin and eosin stain and subsequently reaffirmed with
positive S100 protein stain. Even though schwannoma of the foot had been reported
in the literature, this was an unusual case, as the lesion was presented as a
superficial, ganglion cyst-like lesion on the bottom of the foot.
PMID- 28704616
TI - Inhibition of platelet aggregation ex vivo is repressed in apolipoprotein E
deficient mice.
AB - In the present study, we assessed whether the endogenous platelet inhibitory
mechanisms are altered in the early to moderate stages of the atherosclerotic
process. Apolipoprotein E deficient mice (ApoE-/-), a mouse model of
atherosclerosis, and their wild-type (WT) counterparts were used to assess
agonist-stimulated synthesis of prostacyclin (PGI2), inhibition of platelet
aggregation ex vivo, and intra-platelet cAMP levels. Basal U46619 and ADP
induced platelet aggregation in vitro were increased in ApoE-/- mice at 18-20
weeks in comparison with 8-10 weeks of age. Systemically administered endothelin
1 (ET-1) or bradykinin (BK) inhibited platelet aggregation in a similar fashion
in 8- to 10-week-old ApoE-/- and WT mice, but not in the ApoE-/- mice at 18-20
weeks of age, although both peptides maintained their capacity to increase plasma
levels of the PGI2. Intravenous infusion of PGI2 also failed to inhibit platelet
aggregation ex vivo in 18- to 20-week-old ApoE-/- mice. Interestingly, both BK
and PGI2 retained their ability to increase intraplatelet cAMP in WT and ApoE-/-
mice. Our results suggest that a loss of activity of endogenous
inhibitorymechanisms could contribute to the increased platelet reactivity in
ApoE-/- mice, and that this phenomenon occurs early in the intermediate stage of
the atherosclerotic process.
PMID- 28704617
TI - Resveratrol prevents angiotensin II-induced hypertrophy of vascular smooth muscle
cells through the transactivation of growth factor receptors.
AB - We previously showed that augmented levels of endogenous angiotensin II (AngII)
contribute to vascular smooth muscle cell (VSMC) hypertrophy through the
transactivation of growth factor receptors in spontaneously hypertensive rats.
Resveratrol (RV), a polyphenolic component of red wine, has also been shown to
attenuate AngII-evoked VSMC hypertrophy; however, the molecular mechanism
mediating this response is obscure. The present study was therefore undertaken to
examine whether RV could prevent AngII-induced VSMC hypertrophy through the
transactivation of growth factor receptor and associated signaling pathways.
AngII treatment of VSMC enhanced the protein synthesis that was attenuated
towards control levels by RV pretreatment as well as by the inhibitors of NADPH
oxidase, c-Src, and growth factor receptors. Furthermore, RV pretreatment also
inhibited enhanced levels of superoxide anion, NADPH oxidase activity, increased
expression of NADPH oxidase subunits, and phosphorylation of c-Src, EGF-R, PDGE
R, ERK1/2, and AKT1/2. In conclusion, these results indicate that RV attenuates
AngII-induced VSMC hypertrophy through the inhibition of enhanced oxidative
stress and activation of c-Src, growth factor receptors, and MAPK/AKT signaling.
We suggest that RV could be used as a therapeutic agent in the treatment of
vascular complications associated with hypertension and hypertrophy.
PMID- 28704618
TI - Paracoccidioides brasiliensis presents metabolic reprogramming and secretes a
serine proteinase during murine infection.
AB - Paracoccidoides brasiliensis and Paracoccidioides lutzii, the etiologic agents of
paracoccidioidomycosis, cause disease in healthy and immunocompromised persons in
Latin America. We developed a method for harvesting P. brasiliensis yeast cells
from infected murine lung to facilitate in vivo transcriptional and proteomic
profiling. P. brasiliensis harvested at 6 h post-infection were analyzed using
RNAseq and LC-MSE. In vivo yeast cells had 594 differentially expressed
transcripts and 350 differentially expressed proteins. Integration of
transcriptional and proteomic data indicated that early in infection (6 h), P.
brasiliensis yeast cells underwent a shift in metabolism from glycolysis to beta
oxidation, upregulated detoxifying enzymes to defend against oxidative stress,
and repressed cell wall biosynthesis. Bioinformatics and functional analyses also
demonstrated that a serine proteinase was upregulated and secreted in vivo. To
our knowledge this is the first study depicting transcriptional and proteomic
data of P. brasiliensis yeast cells upon 6 h post-infection of mouse lung.
PMID- 28704619
TI - Advanced glycation end products affect cholesterol homeostasis by impairing ABCA1
expression on macrophages.
AB - Reverse cholesterol transport (RCT), which is intimately linked to high-density
lipoproteins (HDLs), plays a key role in cholesterol homeostasis and the
prevention of atherosclerosis. The goal of the present study was to investigate
the effect of aging and advanced glycation end products (AGEs) on RCT as well as
on other factors that may affect the antiatherogenic property of HDLs. The
transfer of macrophage-derived cholesterol to the plasma and liver and then to
the feces for elimination was significantly lower in aged mice than in young
mice. Chronic injection of d -galactose (D-gal) or AGEs also significantly
reduced RCT (65.3% reduction in [3H]cholesterol levels in the plasma of D-gal
treated mice after 48 h compared with control mice, P < 0.01). The injection of
both D-gal and aminoguanidine hydrochloride increased [3H]cholesterol levels in
the plasma, although the levels were lower than those of control mice. The in
vitro incubation of HDLs with dicarbonyl compounds increased the carbonyl and
conjugated diene content of HDLs and significantly reduced PON1 paraoxonase
activity (87.4% lower than control HDLs, P < 0.0001). Treating J774A.1
macrophages with glycated fetal bovine serum increased carbonyl formation (39.5%
increase, P < 0.003) and reduced ABCA1 protein expression and the capacity of
macrophages to liberate cholesterol (69.1% decrease, P < 0.0001). Our results
showed, for the first time, that RCT is altered with aging and that AGEs
contribute significantly to this alteration.
PMID- 28704620
TI - Rasch Model Analysis Gives New Insights Into the Structural Validity of the
QuickDASH in Patients With Musculoskeletal Shoulder Pain.
AB - Study Design Cross-sectional secondary analysis of a prospective cohort study.
Background The shortened version of the Disabilities of the Arm, Shoulder and
Hand questionnaire (QuickDASH) is a widely used outcome measure that has been
extensively evaluated using classical test theory. Rasch model analysis can
identify strengths and weaknesses of rating scales and goes beyond classical test
theory approaches. It uses a mathematical model to test the fit between the
observed data and expected responses and converts ordinal-level scores into
interval-level measurement. Objective To test the structural validity of the
QuickDASH using Rasch analysis. Methods A prospective cohort study of 1030
patients with shoulder pain provided baseline data. Rasch analysis was conducted
to (1) assess how the QuickDASH fits the Rasch model, (2) identify sources of
misfit, and (3) explore potential solutions to these. Results There was evidence
of multidimensionality and significant misfit to the Rasch model (chi2 = 331.09,
P<.001). Two items had disordered threshold responses with strong floor effects.
Response bias was detected in most items for age and sex. Rescoring resulted in
ordered thresholds; however, the 11-item scale still did not meet the
expectations of the Rasch model. Conclusion Rasch model analysis on the QuickDASH
has identified a number of problems that cannot be easily detected using
traditional analyses. While revisions to the QuickDASH resulted in better fit, a
"shoulder-specific" version is not advocated at present. Caution needs to be
exercised when interpreting results of the QuickDASH outcome measure, as it does
not meet the criteria for interval-level measurement and shows significant
response bias by age and sex. J Orthop Sports Phys Ther 2017;47(9):664-672. Epub
13 Jul 2017. doi:10.2519/jospt.2017.7288.
PMID- 28704621
TI - Making Sense of Low Back Pain and Pain-Related Fear.
AB - Synopsis Pain-related fear is implicated in the transition from acute to chronic
low back pain and the persistence of disabling low back pain, making it a key
target for physical therapy intervention. The current understanding of pain
related fear is that it is a psychopathological problem, whereby people who
catastrophize about the meaning of pain become trapped in a vicious cycle of
avoidance behavior, pain, and disability, as recognized in the fear-avoidance
model. However, there is evidence that pain-related fear can also be seen as a
common-sense response to deal with low back pain, for example, when one is told
that one's back is vulnerable, degenerating, or damaged. In this instance,
avoidance is a common-sense response to protect a "damaged" back. While the fear
avoidance model proposes that when someone first develops low back pain, the
confrontation of normal activity in the absence of catastrophizing leads to
recovery, the pathway to recovery for individuals trapped in the fear-avoidance
cycle is less clear. Understanding pain-related fear from a common-sense
perspective enables physical therapists to offer individuals with low back pain
and high fear a pathway to recovery by altering how they make sense of their
pain. Drawing on a body of published work exploring the lived experience of pain
related fear in people with low back pain, this clinical commentary illustrates
how Leventhal's common-sense model may assist physical therapists to understand
the broader sense-making processes involved in the fear-avoidance cycle, and how
they can be altered to facilitate fear reduction by applying strategies
established in the behavioral medicine literature. J Orthop Sports Phys Ther
2017;47(9):628-636. Epub 13 Jul 2017. doi:10.2519/jospt.2017.7434.
PMID- 28704622
TI - Assessment of Psychometric Properties of Various Balance Assessment Tools in
Persons With Cervical Spondylotic Myelopathy.
AB - Study Design Clinical measurement, cross-sectional, repeated-measures design.
Background Persons with cervical spondylotic myelopathy (CSM) are known to have
balance impairments. The psychometric properties of various balance assessment
tools have not been evaluated in this population. Objective To examine the floor
and ceiling effects, item difficulty and item discrimination index, internal
consistency, reliability, and validity of the Balance Evaluation Systems Test
(BESTest), Mini-BESTest, Brief BESTest, and Berg Balance Scale (BBS) in persons
with CSM. Methods Seventy-two individuals with CSM were evaluated with the above
balance scales. Thirty-two were assessed by a second rater on the same day to
establish interrater reliability, and by the same rater 1 to 2 days later to
assess test-retest reliability. Results Of the 4 balance tools, only the BBS
showed a substantial ceiling effect (skewness, gamma1<-1.0). The BBS also had the
highest proportion (greater than 80%) of easy items. The item discrimination
index was greater than 0.4 for all items in the 4 balance scales. All balance
tests showed good internal consistency (Cronbach alpha>0.8), with excellent test
retest (intraclass correlation coefficient [ICC]2,1>0.80) and interrater
reliability (ICC2,1>0.80). In addition, all balance tests were strongly
correlated with one another (ie, concurrent validity), and with the modified
Japanese Orthopaedic Association score (ie, convergent validity). Their
correlations with the Abbreviated Mental Test were low (ie, discriminant
validity). All 4 balance tests could adequately identify fallers and users of
mobility aids (area under the curve, >0.8) (ie, known-groups validity).
Conclusion The Brief BESTest is the most preferred tool for persons with CSM
because of its excellent reliability, validity, and short administration time,
whereas the BBS is the least preferred due to its substantial ceiling effect. J
Orthop Sports Phys Ther 2017;47(9):673-682. Epub 13 Jul 2017.
doi:10.2519/jospt.2017.7283.
PMID- 28704623
TI - Process of Change in Pain-Related Fear: Clinical Insights From a Single Case
Report of Persistent Back Pain Managed With Cognitive Functional Therapy.
AB - Study Design Single case report with repeated measures over 18 months. Background
Management of persistent low back pain (PLBP) associated with high pain-related
fear is complex. This case report aims to provide clinicians with insight into
the process of change in a person with PLBP and high bending-related fear, who
was managed with an individualized behavioral approach of cognitive functional
therapy. Case Description A retired manual worker with PLBP believed that his
spine was degenerating, that bending would hurt him, and that avoidance was the
only form of pain control. At baseline, he presented high levels of pain-related
fear on the Tampa Scale of Kinesiophobia (score, 47/68) and a high-risk profile
on the Orebro Musculoskeletal Pain Questionnaire (score, 61/100). Unhelpful
beliefs and behaviors led to a vicious cycle of fear and disengagement from
valued life activities. Guided behavioral experiments were used to challenge his
thoughts and protective responses, indicating that his behavior was modifiable
and the pain controllable. Using a multidimensional clinical-reasoning framework,
cognitive functional therapy management was tailored to target key drivers of
PLBP and delivered over 6 sessions in a 3-month period. Outcomes Over an 18-month
clinical journey, he demonstrated improvements in bending-related fear, pain
expectancy, and pain experience, and substantial changes in pain-related fear
(Tampa Scale of Kinesiophobia: 33/68; change, -14 points) and risk profile
(Orebro Musculoskeletal Pain Questionnaire: 36/100; change, -25 points). Clinical
interviews at 6 and 18 months revealed positive changes in mindset, understanding
of pain, perceived pain control, and behavioral responses to pain. Discussion
This case report provides clinicians with an insight to using a multidimensional
clinical-reasoning framework to identify and target the key drivers of the
disorder, and to using cognitive functional therapy to address unhelpful
psychological and behavioral responses to pain in a person with PLBP and high
pain-related fear. Level of Evidence Therapy, level 5. J Orthop Sports Phys Ther
2017;47(9):637-651. Epub 13 Jul 2017. doi:10.2519/jospt.2017.7371.
PMID- 28704624
TI - A Systematic Review of Electromyography Studies in Normal Shoulders to Inform
Postoperative Rehabilitation Following Rotator Cuff Repair.
AB - Study Design Systematic review. Background Electromyography (EMG) has previously
been used to guide postoperative rehabilitation progression following rotator
cuff repair to prevent deleterious loading of early surgical repair. Objective To
review the current literature investigating EMG during rehabilitation exercises
in normal shoulders, and to identify exercises that meet a cut point of 15%
maximal voluntary isometric contraction (MVIC) or less and are unlikely to result
in excessive loading in the early postoperative stages. Methods An electronic
search of MEDLINE via Ovid, Embase, CINAHL, SPORTDiscus, PubMed, and the Cochrane
Library for all years up to June 2016 was performed. Studies were selected in
relation to predefined selection criteria. Pooled mean MVICs were reported and
classified as low (0%-15% MVIC), low to moderate (16%-20% MVIC), moderate (21%
40% MVIC), high (41%-60% MVIC), and very high (greater than 60% MVIC). Results A
search identified 2159 studies. After applying the selection criteria, 20 studies
were included for quality assessment, data extraction, and data synthesis. In
total, 43 exercises spanning passive range of motion, active-assisted range of
motion, and strengthening exercises were evaluated. Out of 13 active-assisted
exercises, 9 were identified as suitable (15% MVIC or less) to load the
supraspinatus and 10 as suitable to load the infraspinatus early after surgery.
All exercises were placed in a theoretical-continuum model, by which general
recommendations could be made for prescription in patients post rotator cuff
repair. Conclusion This review identified passive and active-assisted exercises
that may be appropriate in the early stages after rotator cuff repair. J Orthop
Sports Phys Ther 2017;47(12):931-944. Epub 13 Jul 2017.
doi:10.2519/jospt.2017.7271.
PMID- 28704625
TI - Neuroendocrine Response Following a Thoracic Spinal Manipulation in Healthy Men.
AB - Study Design Controlled laboratory study. Background Spinal manipulation (SM) can
trigger a cascade of responses involving multiple systems, including the
sympathetic nervous system and the endocrine system, specifically, the
hypothalamic-pituitary axis. However, no manual therapy study has investigated
the neuroendocrine response to SM (ie, sympathetic nervous system-hypothalamic
pituitary axis) in the same trial. Objective To determine short-term changes in
sympathetic nervous system activity, heart rate variability, and endocrine
activity (cortisol, testosterone, and testosterone-cortisol [T/C] ratio)
following a thoracic SM. Methods Twenty-four healthy men aged between 18 and 45
years were randomized into 2 groups: thoracic SM (n = 12) and sham (n = 12).
Outcome measures were salivary cortisol (micrograms per deciliter), salivary
testosterone (picograms per milliliter), T/C ratio, heart rate variability, and
changes in oxyhemoglobin concentration of the right calf muscle (micromoles per
liter). Measurements were done before and at 5 minutes, 30 minutes, and
approximately 6 hours after intervention. Results A statistically significant
group-by-time interaction was noted for T/C ratio (P<.05) and salivary cortisol
(P<.01) concentrations. Significant between-group differences were noted for
salivary cortisol concentration at 5 minutes (mean difference, 0.35; 95%
confidence interval: 0.12, 0.6; interaction: P<.01) and for T/C ratio at 6 hours
postintervention (mean difference, -0.09; 95% confidence interval: -0.16, -0.04;
P = .02). However, SM did not differentially alter oxyhemoglobin, testosterone,
or heart rate variability relative to responses in the sham group. Conclusion
Thoracic SM resulted in an immediate decrease in salivary cortisol concentration
and reduced T/C ratio 6 hours after intervention. A pattern of immediate
sympathetic excitation was also observed in the SM group. J Orthop Sports Phys
Ther 2017;47(9):617-627. Epub 13 Jul 2017. doi:10.2519/jospt.2017.7348.
PMID- 28704626
TI - The Effectiveness of Neural Mobilization for Neuromusculoskeletal Conditions: A
Systematic Review and Meta-analysis.
AB - Study Design Systematic review with meta-analysis. Objectives To determine the
efficacy of neural mobilization (NM) for musculoskeletal conditions with a
neuropathic component. Background Neural mobilization, or neurodynamics, is a
movement-based intervention aimed at restoring the homeostasis in and around the
nervous system. The current level of evidence for NM is largely unknown. Methods
A database search for randomized trials investigating the effect of NM on
neuromusculoskeletal conditions was conducted, using standard methods for article
identification, selection, and quality appraisal. Where possible, studies were
pooled for meta-analysis, with pain, disability, and function as the primary
outcomes. Results Forty studies were included in this review, of which 17 had a
low risk of bias. Meta-analyses could only be performed on self-reported
outcomes. For chronic low back pain, disability (Oswestry Disability
Questionnaire [0-50]: mean difference, -9.26; 95% confidence interval [CI]:
14.50, -4.01; P<.001) and pain (intensity [0-10]: mean difference, -1.78; 95% CI:
-2.55, -1.01; P<.001) improved following NM. For chronic neck-arm pain, pain
improved (intensity: mean difference, -1.89; 95% CI: -3.14, -0.64; P<.001)
following NM. For most of the clinical outcomes in individuals with carpal tunnel
syndrome, NM was not effective (P>.11) but showed some positive
neurophysiological effects (eg, reduced intraneural edema). Due to a scarcity of
studies or conflicting results, the effect of NM remains uncertain for various
conditions, such as postoperative low back pain, cubital tunnel syndrome, and
lateral epicondylalgia. Conclusion This review reveals benefits of NM for back
and neck pain, but the effect of NM on other conditions remains unclear. Due to
the limited evidence and varying methodological quality, conclusions may change
over time. Level of Evidence Therapy, level 1a. J Orthop Sports Phys Ther
2017;47(9):593-615. Epub 13 Jul 2017. doi:10.2519/jospt.2017.7117.
PMID- 28704627
TI - Task-Specific Training for Adults With Chronic Knee Pain: A Case Series.
AB - Study Design Case series. Background Recent evidence suggests that traditional
impairment-based rehabilitation approaches for patients with knee pain may not
result in improved function or reduced disability. This case series describes a
novel task-specific training approach to exercise therapy for patients with
chronic knee pain and reports changes in measures of clinical outcome (pain and
physical function) following participation in the training program. Case
Description Seven patients with chronic knee pain aged 40 years or older were
included. Each reported at least "moderate" difficulty with sit-to-stand
transfers, floor transfers, and/or stair negotiation at baseline. Experienced
physical therapists provided between 8 and 16 treatment sessions focusing on
improving performance of difficult or painful tasks. Outcomes A majority of
patients demonstrated clinically important improvements in both patient-rated
outcomes (Knee injury and Osteoarthritis Outcome Score, numeric pain-rating
scale, modified Arthritis Self-Efficacy Scale) and performance-based outcomes (30
second chair-rise test, timed stair-climb test, floor transfer test, Performance
Assessment of Self-Care Skills). Discussion A task-specific training approach for
patients with chronic knee pain was described and yielded considerable
improvement in pain and function for most of the individuals in this case series.
Larger studies are needed to determine how task-specific training compares with
more traditional impairment-based exercise approaches for chronic knee pain.
Level of Evidence Therapy, level 5. J Orthop Sports Phys Ther 2017;47(8):548-556.
doi:10.2519/jospt.2017.7349.
PMID- 28704628
TI - Positive Affect Is Associated With Reduced Fixation in a Realistic Medical
Simulation.
AB - OBJECTIVE: This study extends previous research by exploring the association
between mood states (i.e., positive and negative affect) and fixation in
practicing anesthetists using a realistic medical simulation. BACKGROUND: The
impact of practitioner emotional states on fixation is a neglected area of
research. Emerging evidence is demonstrating the role of positive affect in
facilitating problem solving and innovation, with demonstrated implications for
practitioner fixation. METHOD: Twelve practicing anesthetists (4 females; Mage=
39 years; SD = 6.71) were involved in a medical simulation. Prior to the
simulation, practitioners rated the frequency they had experienced various
positive and negative emotions in the previous three days. During the simulation,
the patient deteriorated rapidly, and anesthetists were observed for their degree
of fixation. After the simulation, practitioners indicated the frequency of these
same emotions during the simulation. RESULTS: Nonparametric correlations were
used to explore the independent relationships between positive and negative
affect and the behavioral measures. Only positive affect impacted the likelihood
of fixation. Anesthetists who reported more frequent recent positive affect in
the three days prior to the simulation and during the simulation tended to be
less fixated as judged by independent raters, identified a decline in patient
oxygen saturation more quickly, and more rapidly implemented the necessary
intervention (surgical cricothyroidotomy). CONCLUSION: These findings have some
real-world implications for positive affect in patient safety. APPLICATION: This
research has broad implications for professions where fixation may impair
practice. This research suggests that professional training should teach
practitioners to identify their emotions and understand the role of these
emotions in fixation.
PMID- 28704629
TI - Enhanced Hazard Analysis and Risk Assessment for Human-in-the-Loop Systems.
AB - OBJECTIVE: The objective of this study was to enhance the existing system hazard
analysis (SHA) technique by introducing the concepts of human and automation
reliability quantification as well as fuzzy classification of system risks. These
enhancements led to formulation of a new overall system risk-reliability score.
BACKGROUND: Many system safety analysis methods focus on individual physical
component failure. Some human reliability analyses (HRA) consider human
automation interaction in determining system failure rates. There is no system
safety analysis technique that quantifies the impact of human and automation
reliability on the risk of hazard exposure. METHOD: Classification of the
probability and severity of hazard exposure is typically made in terms of
linguistic rather than numerical variables. Fuzzy sets are applicable for
transforming linguistic classifications to numerical quantities. We focused on
using fuzzy sets to define overlapping bands of system risk exposure with
reference to the hazard risk categories defined in MIL-STD 882B. Fuzzy sets were
also used for human-automated system reliability classification. RESULTS:
Introduction of human and automation reliability assessment in the SHA allows for
definition of a system risk-reliability modeling space. The enhanced SHA (E-SHA)
technique yields a mishap risk index, which is projected based on a composite
assessment of human-automated system reliability at the time of operation. The E
SHA was compared with one of the most advanced HRA techniques. CONCLUSION: The E
SHA technique supports broader safety control recommendations and provides
comparable, if not more detailed, results than prior systems safety and HRA
techniques.
PMID- 28704630
TI - Relationship Between BMI and Fatigability Is Task Dependent.
AB - OBJECTIVE: The objective of the current study was to determine the effect of body
mass index (BMI) on fatigability of three different muscle groups at four
different work intensities. METHODS: Forty-nine normal-weight, 50 overweight, and
43 obese adults (32.1 +/- 9.2 years; 50% males) performed fatiguing handgrip,
shoulder flexion, and trunk extension exertions at 20%, 40%, 60%, and 80% of the
associated maximum voluntary contractions. RESULTS: Obese adults demonstrated 22%
to 30% shorter endurance times than normal-weight adults, but this was only
observed at lower intensities and with larger and more postural muscles of the
shoulder and low back. Strength and fatigue-related strength loss remained
comparable across BMI groups in both males and females in these task-specific
conditions. Obesity was associated with faster progression in perception of
effort at low-intensity shoulder and trunk exertions. While males were stronger
than females across all muscle groups, females exhibited greater shoulder fatigue
resistance than males at lower intensity levels. CONCLUSION: Findings indicate
that the relationship between obesity and fatigability is task dependent.
APPLICATION: These findings provide initial evidence on the impact of obesity on
worker capacity. Future work that extends the current investigation to include
more occupationally relevant scenarios are needed to facilitate occupational task
(re)design and assessment practices, such that altered work capacities of two
thirds of the working population are accommodated.
PMID- 28704631
TI - Driver Movement Patterns Indicate Distraction and Engagement.
AB - Objective This research considers how driver movements in video clips of
naturalistic driving are related to observer subjective ratings of distraction
and engagement behaviors. Background Naturalistic driving video provides a unique
window into driver behavior unmatched by crash data, roadside observations, or
driving simulator experiments. However, manually coding many thousands of hours
of video is impractical. An objective method is needed to identify driver
behaviors suggestive of distracted or disengaged driving for automated computer
vision analysis to access this rich source of data. Method Visual analog scales
ranging from 0 to 10 were created, and observers rated their perception of driver
distraction and engagement behaviors from selected naturalistic driving videos.
Driver kinematics time series were extracted from frame-by-frame coding of driver
motions, including head rotation, head flexion/extension, and hands on/off the
steering wheel. Results The ratings were consistent among participants. A
statistical model predicting average ratings from the kinematic features
accounted for 54% of distraction rating variance and 50% of engagement rating
variance. Conclusion Rated distraction behavior was positively related to the
magnitude of head rotation and fraction of time the hands were off the wheel.
Rated engagement behavior was positively related to the variation of head
rotation and negatively related to the fraction of time the hands were off the
wheel. Application If automated computer vision can code simple kinematic
features, such as driver head and hand movements, then large-volume naturalistic
driving videos could be automatically analyzed to identify instances when drivers
were distracted or disengaged.
PMID- 28704632
TI - Measuring Memory and Attention to Preview in Motion.
AB - Objective Use perceptual-motor responses to perturbations to reveal the spatio
temporal detail of memory for the recent past and attention to preview when
participants track a winding roadway. Background Memory of the recently passed
roadway can be inferred from feedback control models of the participants' manual
movement patterns. Similarly, attention to preview of the upcoming roadway can be
inferred from feedforward control models of manual movement patterns. Method
Perturbation techniques were used to measure these memory and attention
functions. Results In a laboratory tracking task, the bandwidth of lateral
roadway deviations was found to primarily influence memory for the past roadway
rather than attention to preview. A secondary auditory/verbal/vocal memory task
resulted in higher velocity error and acceleration error in the tracking task but
did not affect attention to preview. Attention to preview was affected by the
frequency pattern of sinusoidal perturbations of the roadway. Conclusion
Perturbation techniques permit measurement of the spatio-temporal span of memory
and attention to preview that affect tracking a winding roadway. They also
provide new ways to explore goal-directed forgetting and spatially distributed
attention in the context of movement. More generally, these techniques provide
sensitive measures of individual differences in cognitive aspects of action.
Application Models of driving behavior and assessment of driving skill may
benefit from more detailed spatio-temporal measurement of attention to preview.
PMID- 28704633
TI - The Influence of Hand Immersion Duration on Manual Performance.
AB - OBJECTIVE: To investigate the effect of hand immersion duration on manipulative
ability and tactile sensitivity. BACKGROUND: Individuals in maritime settings
often work with hands that have been immersed in water. Although research has
shown that hand immersion duration differentially impacts skin adhesion and
tactile sensitivity, the effect of hand immersion on manipulative ability has not
been directly tested. Given how critical manipulative ability is for the safety
and performance of those working at sea, the effect of hand immersion duration on
manual performance was investigated. METHOD: Tests of manipulative ability
(Purdue Pegboard, Grooved Pegboard, reef knot untying) and tactile sensitivity
(Touch-Test) were completed following no-exposure, short-exposure, and long
exposure hand immersions in thermoneutral water. RESULTS: Compared to the no
immersion condition, the Purdue Pegboard performance was reduced in both
immersion conditions (short exposure, -11%; long exposure, -8%). A performance
decrement was only observed in the short exposure condition (+15% in time to
complete task) for the reef knot untying task. There were no statistical
differences in the Grooved Pegboard or Touch-Test scores between exposure
conditions. CONCLUSION: Immersing the hands in water decreases manipulative
ability except for when object properties reduce the slipperiness between the
hand and object. APPLICATION: Manual performance in a wet environment may be
conserved by designing tools and objects with edges and textures that can offset
the slipperiness of wet hands. To maintain safety, the time requirements for
working with wet hands needs to be considered.
PMID- 28704634
TI - Comparison of Sedentary Behaviors in Office Workers Using Sit-Stand Tables With
and Without Semiautomated Position Changes.
AB - OBJECTIVE: We compared usage patterns of two different electronically controlled
sit-stand tables during a 2-month intervention period among office workers.
BACKGROUND: Office workers spend most of their working time sitting, which is
likely detrimental to health. Although the introduction of sit-stand tables has
been suggested as an effective intervention to decrease sitting time, limited
evidence is available on usage patterns of sit-stand tables and whether patterns
are influenced by table configuration. METHOD: Twelve workers were provided with
standard sit-stand tables (nonautomated table group) and 12 with semiautomated
sit-stand tables programmed to change table position according to a preset
pattern, if the user agreed to the system-generated prompt (semiautomated table
group). Table position was monitored continuously for 2 months after introducing
the tables, as a proxy for sit-stand behavior. RESULTS: On average, the table was
in a "sit" position for 85% of the workday in both groups; this percentage did
not change significantly during the 2-month period. Switches in table position
from sit to stand were, however, more frequent in the semiautomated table group
than in the nonautomated table group (0.65 vs. 0.29 hr-1; p = .001). CONCLUSION:
Introducing a semiautomated sit-stand table appeared to be an attractive
alternative to a standard sit-stand table, because it led to more posture
variation. APPLICATION: A semiautomated sit-stand table may effectively
contribute to making postures more variable among office workers and thus aid in
alleviating negative health effects of extensive sitting.
PMID- 28704635
TI - Rehabilitation and Improvement of Health-Related Quality-of-Life Detriments in
Individuals With Chronic Ankle Instability: A Meta-Analysis.
AB - OBJECTIVE: To conduct a systematic review with meta-analysis assessing the
effectiveness of conservative rehabilitation programs for improving health
related quality of life (HRQL) in individuals with chronic ankle instability
(CAI). DATA SOURCES: PubMed, MEDLINE, CINAHL, and SPORTDiscus were searched
from inception to January 2016. STUDY SELECTION: Studies were included if the
researchers examined the effects of a conservative rehabilitation protocol in
individuals with CAI, used validated patient-reported outcomes (PROs) to quantify
participant-perceived HRQL, and provided adequate data to calculate the effect
sizes (ESs) and 95% confidence intervals (CIs). Studies were excluded if the
authors evaluated surgical interventions, prophylactic taping, or bracing
applications or examined only the immediate effects of 1 treatment session. DATA
EXTRACTION: Two investigators independently assessed methodologic quality using
the Physiotherapy Evidence Database (PEDro) Scale. Studies were considered low
quality if fewer than 60% of the criteria were met. Level of evidence was
assessed using the Strength of Recommendation Taxonomy. Preintervention and
postintervention sample sizes, means, and standard deviations of PROs were
extracted. DATA SYNTHESIS: A total of 15 studies provided 24 participant groups
that were included in the analysis. Seven high-quality studies with a median
PEDro score of 50% (range = 10%-80%) and a median level of evidence of 2 (range =
1-2) were identified. The magnitudes of preintervention to postintervention PRO
differences were examined using bias-corrected Hedges g ESs. Random-effects meta
analysis was performed to synthesize PRO changes across all participant groups.
Positive ES values indicated better PRO scores at postintervention than at
preintervention. The alpha level was set at .05. Meta-analysis revealed a strong
ES with a nonoverlapping 95% CI (ES = 1.20, CI = 0.80, 1.60; P < .001),
indicating HRQL improved after conservative rehabilitation. CONCLUSIONS: Based
on the quality of the evidence and the results of the meta-analysis, grade A
evidence showed that conservative rehabilitation produces large improvements in
HRQL for people with CAI.
PMID- 28704636
TI - Partial Superficial, Superficial, and Total Parotidectomy in the Management of
Benign Parotid Gland Tumors: A 10-Year Prospective Study of 205 Patients.
AB - PURPOSE: The aim of this report is to present an overview of the authors'
experience in treating parotid gland tumors for a period of 10 years. This report
describes patients' demographics, surgical outcomes, and complications and
discusses the management of benign disease with particular emphasis on the
importance of facial nerve dissection. PATIENTS AND METHODS: A total of 205
consecutive patients with different parotid gland tumors underwent surgery at
Northampton General Hospital (Northampton, UK) from October 2000 to November
2010. Data were prospectively collected and entered into an electronic database.
Patients' demographics, clinical tumor size, type of operation, fine-needle
aspiration result, facial nerve status, final histopathologic report, and
intraoperative and postoperative complications were recorded and analyzed.
RESULTS: This study confirmed that good results in low recurrence rate and
minimal risk of facial nerve weakness can be achieved with operations less
aggressive than traditional superficial parotidectomy, such as partial
superficial parotidectomy. Transient facial nerve palsy was significantly more
frequent after total (40%; P < .001) and superficial (28%; P < .05)
parotidectomy, respectively, than after partial superficial parotidectomy (9.6%).
CONCLUSION: Because the risk or recurrence is higher when surgery is performed by
inexperienced surgeons, the authors advocate that parotid gland surgery should be
performed by adequately trained operators and the surgical specimen ideally
should be examined by a histopathologist experienced in the diagnosis of salivary
gland tumors. Recurrence rate for these tumors increases with time; therefore,
long-term follow-up is required for these patients.
PMID- 28704637
TI - Evaluation of the Mandibular Lingual Canal and Anterior Loop Length to Minimize
Complications Associated With Anterior Mandibular Surgeries: A Cone-Beam Computed
Tomography Study.
AB - PURPOSE: This retrospective study evaluated the localization, incidence, and
dimensions of the mandibular lingual canal and the anterior loop in the Taiwanese
population using the simulation and visual interpretation of cone-beam computed
tomography to minimize complications during symphysis block surgical procedures.
MATERIALS AND METHODS: The sample population consisted of 215 patients (105 men
and 110 women; mean age, 57 yr). The median lingual canal, symphysis bone
thickness, and anterior loop length were defined and calculated using cone-beam
computed tomography and 3-dimensional reconstructed images. The correlation of
all data for men and women was assessed and analyzed statistically using unpaired
t tests. RESULTS: All patients exhibited at least 1 median lingual canal in the
symphysis, and the diameter of the main branch ranged from 0.21 to 1.48 mm (mean,
0.85 mm), with relevant differences between genders (longer in men than in
women). A harvesting depth of 4 mm for the distance from the buccal bone to the
terminal end of the median lingual canal resulted in a risk of neurovascular
injury (13.0%); this risk was notably higher in women (19.1%) than in men (6.7%).
The right and left anterior loop lengths ranged from 0 to 5.46 mm (mean, 2.60 mm)
and from 0 to 5.57 mm (mean, 2.61 mm), respectively, with no relevant differences
between genders or sides. CONCLUSIONS: The results suggest that routine cone-beam
computed tomographic examinations before surgical interventions in the symphysis
region are necessary because of the numerous complicated anatomic variations.
PMID- 28704638
TI - Regulator of Calcineurin 3 Ameliorates Autoimmune Arthritis by Suppressing Th17
Cell Differentiation.
AB - Regulator of calcineurin 3 (RCAN3), an endogenous regulator of the calcineurin
nuclear factor of activated T cells (NFAT) signaling pathway, inhibits the
phosphatase activity of calcineurin, the nuclear translocation of NFAT, and the
NFAT downstream pathway. To investigate the effects of RCAN3 on T-cell regulatory
function and the development and progression of inflammatory arthritis, we
studied the effects of RCAN3 transfection on regulation of Th17 cell
differentiation in a murine T-lymphoma cell line and primary splenic CD4+ T
cells. Overexpression of RCAN3 suppressed Th17 cell differentiation through the
down-regulation of RAR receptor orphan receptor gammaT mRNA and up-regulation of
forkhead box P3 mRNA. In mice with collagen-induced arthritis, injection of an
RCAN3-overexpression vector controlled arthritis development in vivo. Injection
of RCAN3 reduced the formation of osteoclasts and expression of inflammatory
cytokines in vivo. Antioxidants stimulated the expression of RCAN3 in vitro, and
combination therapy with pcDNA-RCAN3 had a synergistic suppressive effect on the
development of arthritis. These data suggest that RCAN3 may be an effective
treatment for rheumatoid arthritis.
PMID- 28704639
TI - A sense of agency: An ethnographic exploration of being awake during mechanical
ventilation in the intensive care unit.
AB - BACKGROUND: There is a current trend towards lighter or no sedation of
mechanically ventilated patients in the intensive care unit. The advantages of
less sedation have been demonstrated as shorter duration of mechanical
ventilation and reduced length of stay in the intensive care unit and hospital.
Non-sedated patients are more awake during mechanical ventilation, but little is
known about how this affects the intensive care patient. AIM: To explore
patients' experiences of being awake during critical illness and mechanical
ventilation in the intensive care unit. DESIGN & METHODS: The study was based on
Interpretive Description, an applied inductive, qualitative approach with an
ethnographic exploration of the patient experience. A longitudinal perspective
was obtained through 13 months of fieldwork followed by two patient interviews
after intensive care and after hospital discharge. Data were analyzed using
thematic analysis. SETTING & PARTICIPANTS: The fieldwork was conducted in two
intensive care units at a university hospital in Denmark, where the no sedation
strategy for mechanically ventilated patients was implemented. Twenty-eight
patients were observed in the intensive care unit. Twenty patients, who had been
awake for most of the time on mechanical ventilation, were interviewed during the
first week after discharge from intensive care. Thirteen of these patients were
interviewed again two to four months after discharge. FINDINGS: Three themes were
identified: "A sense of agency", "The familiar in the unfamiliar situation" and
"Awareness of surrounding activities". Patients had the ability to interact from
the first days of critical illness and a sense of agency was expressed through
initiating, directing and participating in communication and other activities.
Patients appreciated competent and compassionate nurses who were attentive and
involved them as individual persons. Initiatives to enhance familiar aspects such
as relatives, personal items and care, continuity and closeness of nurses
contributed to the patients' experience of feeling safe and secure in the
unfamiliar setting. Patients were aware of the surrounding activities and felt
powerless when ignored by the staff and were affected when witnessing fellow
patients' suffering. CONCLUSION: Being awake during mechanical ventilation
entailed new opportunities and challenges for critically ill patients. Patients
found themselves at the interface between agency and powerlessness as they were
able to interact, yet were bound by contextual factors such as bodily weakness,
technology, spatial position and relational aspects. This knowledge is important
to develop patient-centered nursing practice in the context of lighter sedation.
PMID- 28704640
TI - The pitfalls of biomarker-based classification schemes.
PMID- 28704641
TI - Giants in Obstetrics and Gynecology: A profile of Donald R. Coustan, MD.
PMID- 28704642
TI - Infections after shoulder arthroplasty are correlated with higher anesthetic risk
score: a case-control study in Brazil.
AB - PURPOSES: Shoulder arthroplasty (SA) has been performed by many years for the
treatment of several conditions, including osteoarthritis and proximal humeral
fractures following trauma. Surgical site infection (SSI) following Shoulder
arthroplasty remains a challenge, contributing to increased morbidity and costs.
Identification of risk factors may help implementing adequate strategies to
prevent infection. We aimed to identify pre- and intra-operative risk factors
associated with deep infections after Shoulder arthroplasty. METHODS: An
unmatched case-control study was conducted to describe the prevalence, clinical
and microbiological findings, and to evaluate patient and surgical risk factors
for prosthetic shoulder infection (PSI), among 158 patients who underwent SA due
to any reason, at a tertiary public university institution. Risk factors for PSI
was assessed by uni- and multivariate analyses using multiple logistic
regression. RESULTS: 168 SA from 158 patients were analyzed, with an overall
infection rate of 9.5% (16/168 cases). Subjects undergoing SA with American
Society of Anesthesiologists (ASA) grade III or higher (odds ratio [OR]=5.30, 95%
confidence interval [CI]=1.58-17.79, p<0.013) and presenting local hematoma after
surgery (odds ratio [OR]=7.10, 95% confidence interval [CI]=1.09-46.09, p=0.04)
had higher risk for PSI on univariate analysis. However, only ASA score grade III
or higher remained significant on multivariate analysis (OR=4.74, 95% CI=1.33
16.92, p=0.016). Gram-positive cocci and Gram-negative bacilli were equally
isolated in 50% of cases; however, the most commonly detected bacterium was
Pseudomonas aeruginosa (18.7%). CONCLUSION: This study provides evidence
suggesting that patient-related known factors such as higher ASA score
predisposes to shoulder arthroplasty-associated infection. Furthermore, unusual
pathogens associated with PSI were identified.
PMID- 28704643
TI - Multidisciplinary training of cancer specialists in Europe.
AB - The best care for patients with cancer is most likely to be achieved when
decisions about diagnosis, staging and treatment are made at multidisciplinary
and multiprofessional meetings, preferably when all the professional expertise
relevant to the patient's condition is gathered together. Questionnaires were
sent to National Societies of Radiation Oncology and Medical Oncology concerning
similarities and differences in training programs and multidisciplinary care in
member states in Europe. Results indicated wide variation in training systems and
practice. Data were lacking for Surgery because Surgical Oncology is not
recognised as a speciality in the EU and most specialist training in cancer
surgery is organ based. A period of time in cross-disciplinary training in each
of the other two disciplines for all trainees in Medical Oncology, Radiation
Oncology and Surgical Oncology (including all surgeons training in cancer
surgery) is recommended. This is likely to improve the value of multidisciplinary
meetings and may result in improved patient care. The Expert Group on Cancer
Control of the European Commission has endorsed this recommendation.
PMID- 28704644
TI - Amide proton transfer-weighted magnetic resonance image-guided stereotactic
biopsy in patients with newly diagnosed gliomas.
AB - PURPOSE: Pathological assessment using World Health Organization (WHO) criteria
is the gold standard for diagnosis of gliomas. However, the accuracy of diagnosis
is limited by tissue sampling, particularly for infiltrating, heterogeneous
tumours. We assessed the accuracy of amide proton transfer-weighted (APTw)
magnetic resonance imaging (MRI)-guided tissue sampling to identify regions of
high-grade glioma via radiographic-histopathologic correlation in patients with
newly suspected glioma. PATIENTS AND METHODS: Twenty-four patients with
previously undiagnosed gliomas underwent a volumetric APTw MRI prior to their
first neurosurgical procedure. A total of 70 specimens were collected via APTw
image-directed stereotactic biopsy. Cellularity, necrosis, proliferation and
glioma WHO grade were analysed for all specimens and correlated with
corresponding APTw signal intensities. RESULTS: Thirty-three specimens displayed
grade-II pathology, 14 grade-III, 15 grade-IV, and eight specimens revealed only
peritumoural oedema. Multiple glioma grades were found within a single lesion in
six patients. APTw signal intensities of the biopsied sites and the maximum APTw
values across all biopsied sites in each patient were significantly higher for
high-grade versus low-grade specimens. APTw signal intensities were significantly
positively correlated with cellularity (R = 0.757) and proliferation (R = 0.538).
Multiple linear regression analysis showed that tumour cellularity and
proliferation index were the best predictors of APTw signal intensities.
CONCLUSION: APTw imaging identified tumour areas of higher cellularity and
proliferation, allowing identification of high-grade regions within heterogeneous
gliomas. APTw imaging can be readily translated for more widespread use and can
assist diagnostic neurosurgical procedures by increasing the accuracy of tumour
sampling in patients with infiltrating gliomas.
PMID- 28704645
TI - Meta-analysis and systematic review of studies on the effectiveness of HIV stigma
reduction programs.
AB - OBJECTIVE: The present study conducted a meta-analysis and systematic review on
studies evaluating the effectiveness of stigma reduction programs in improving
knowledge and reducing negative attitudes towards people living with HIV (PLHIV).
RESULTS: Meta-analysis (k = 42 studies) found significant and small effect sizes
in the improvement of the participants' knowledge of HIV/AIDS from interventions
with (Cohen's d = 0.48, 95% CI [0.30, 0.66]) and without control groups (Cohen's
d = 0.42, 95% CI [0.28, 0.57]). Significant and small effect sizes were found in
the improvement of the participants' attitudes toward PLHIV from interventions
with (Cohen's d = 0.39, 95% CI [0.23, 0.55]) and without control groups (Cohen's
d = 0.25, 95% CI [0.11, 0.39]). Significant and small effect sizes were sustained
at the follow-up assessments. Subgroup analysis showed that number of
intervention sessions, intervention settings, and sample type significantly
moderated the effect sizes in the meta-analysis. Findings from the systematic
review of 35 studies indicated that most of the included studies showed positive
results in reducing negative attitudes toward PLHIV and improving HIV-related
knowledge. Most of the included studies tended to have low methodological
quality. CONCLUSION: The present meta-analysis and systematic review indicated
that the studies generally found small improvement in HIV-related knowledge and
reduction in negative attitudes towards PLHIV among the stigma reduction programs
being evaluated. High-quality stigma reduction programs with multidimensional
stigma indicators and psychometrically sound outcome measures are highly
warranted.
PMID- 28704646
TI - Skin Dysbiosis Goes "Off-Leish".
AB - There is increasing interest in the contribution of microbes to skin disease. In
this issue of Cell Host & Microbe, Gimblet et al. (2017) demonstrate that
cutaneous leishmaniasis alters the human skin microbiota. In mice, this dysbiosis
is transferable to naive animals, where it augments skin inflammation and disease
severity.
PMID- 28704647
TI - HIV-1-Mediated Downmodulation of HLA-C Impacts Target Cell Recognition and
Antiviral Activity of NK Cells.
AB - It was widely accepted that HIV-1 downregulates HLA-A/B to avoid CTL recognition
while leaving HLA-C unaltered in order to prevent NK cell activation by engaging
inhibitory NK cell receptors, but it was recently observed that most primary
isolates of HIV-1 can mediate HLA-C downmodulation. Now we report that HIV-1
mediated downmodulation of HLA-C was associated with reduced binding to its
respective inhibitory receptors. Despite this, HLA-C-licensed NK cells displayed
reduced antiviral activity compared to their unlicensed counterparts, potentially
due to residual binding to the respective inhibitory receptors. Nevertheless, NK
cells were able to sense alterations of HLA-C expression demonstrated by
increased antiviral activity when exposed to viral strains with differential
abilities to downmodulate HLA-C. These results suggest that the capability of HLA
C-licensed NK cells to control HIV-1 replication is determined by the strength of
KIR/HLA-C interactions and is thus dependent on both host genetics and the extent
of virus-mediated HLA-C downregulation.
PMID- 28704648
TI - Diabetes Enhances IL-17 Expression and Alters the Oral Microbiome to Increase Its
Pathogenicity.
AB - Diabetes is a risk factor for periodontitis, an inflammatory bone disorder and
the greatest cause of tooth loss in adults. Diabetes has a significant impact on
the gut microbiota; however, studies in the oral cavity have been inconclusive.
By 16S rRNA sequencing, we show here that diabetes causes a shift in oral
bacterial composition and, by transfer to germ-free mice, that the oral
microbiota of diabetic mice is more pathogenic. Furthermore, treatment with IL-17
antibody decreases the pathogenicity of the oral microbiota in diabetic mice;
when transferred to recipient germ-free mice, oral microbiota from IL-17-treated
donors induced reduced neutrophil recruitment, reduced IL-6 and RANKL, and less
bone resorption. Thus, diabetes-enhanced IL-17 alters the oral microbiota and
renders it more pathogenic. Our findings provide a mechanistic basis to better
understand how diabetes can increase the risk and severity of tooth loss.
PMID- 28704650
TI - Bacteria Tell Us How to Protect Our Intestine.
AB - The inner colon mucus layer capacity to separate bacteria from the epithelium is
dependent on bacterial colonizers signaling to the host epithelium. In this issue
of Cell Host & Microbe, Wlodarska et al. (2017) demonstrate that the mucin
utilizing Peptostreptococcus russellii protects the host from inflammatory
disease via metabolite signals.
PMID- 28704649
TI - Indoleacrylic Acid Produced by Commensal Peptostreptococcus Species Suppresses
Inflammation.
AB - Host factors in the intestine help select for bacteria that promote health.
Certain commensals can utilize mucins as an energy source, thus promoting their
colonization. However, health conditions such as inflammatory bowel disease (IBD)
are associated with a reduced mucus layer, potentially leading to dysbiosis
associated with this disease. We characterize the capability of commensal species
to cleave and transport mucin-associated monosaccharides and identify several
Clostridiales members that utilize intestinal mucins. One such mucin utilizer,
Peptostreptococcus russellii, reduces susceptibility to epithelial injury in
mice. Several Peptostreptococcus species contain a gene cluster enabling
production of the tryptophan metabolite indoleacrylic acid (IA), which promotes
intestinal epithelial barrier function and mitigates inflammatory responses.
Furthermore, metagenomic analysis of human stool samples reveals that the genetic
capability of microbes to utilize mucins and metabolize tryptophan is diminished
in IBD patients. Our data suggest that stimulating IA production could promote
anti-inflammatory responses and have therapeutic benefits.
PMID- 28704651
TI - Synergy between the Host Immune System and Bacteriophage Is Essential for
Successful Phage Therapy against an Acute Respiratory Pathogen.
AB - The rise of multi-drug-resistant (MDR) bacteria has spurred renewed interest in
the use of bacteriophages in therapy. However, mechanisms contributing to phage
mediated bacterial clearance in an animal host remain unclear. We investigated
the effects of host immunity on the efficacy of phage therapy for acute pneumonia
caused by MDR Pseudomonas aeruginosa in a mouse model. Comparing efficacies of
phage-curative and prophylactic treatments in healthy immunocompetent, MyD88
deficient, lymphocyte-deficient, and neutrophil-depleted murine hosts revealed
that neutrophil-phage synergy is essential for the resolution of pneumonia.
Population modeling of in vivo results further showed that neutrophils are
required to control both phage-sensitive and emergent phage-resistant variants to
clear infection. This "immunophage synergy" contrasts with the paradigm that
phage therapy success is largely due to bacterial permissiveness to phage
killing. Lastly, therapeutic phages were not cleared by pulmonary immune effector
cells and were immunologically well tolerated by lung tissues.
PMID- 28704652
TI - Environmental Stress Causes Lethal Neuro-Trauma during Asymptomatic Viral
Infections.
AB - Asymptomatic infections often proceed undetected, yet can still prime the host to
be sensitive to secondary environmental stress. While the mechanisms underlying
disease caused by asymptomatic infections are unknown, it is believed that
productive pathogen replication is required. We report that the environmental
stress of carbon dioxide (CO2) anesthesia converts an asymptomatic rhabdovirus
infection in Drosophila to one that is lethal. This lethality results from a pool
of infectious virus in glial cells and is regulated by the antiviral RNAi pathway
of the host. CO2 sensitivity is caused by the fusogenic activity of the viral
glycoprotein, which results in fusion of neurons and glia. Expression of the
viral glycoprotein, but not a fusion defective mutant, is sufficient to cause CO2
sensitivity, which can occur even in the absence of productive viral replication.
These findings highlight how viral proteins, independent of pathogen replication,
may predispose hosts to life-threatening environmental stress.
PMID- 28704653
TI - Double the Trouble When Herpesviruses Join Hands.
AB - KSHV is the etiologic agent of PEL-an aggressive lymphoma. Interestingly, EBV
concurrently exists in nearly 70% of PEL cases. In this issue of Cell Host &
Microbe, McHugh et al. (2017) develop humanized mouse models for EBV/KSHV co
infection and identify their complementary effect on in vivo tumor formation.
PMID- 28704654
TI - Persistent KSHV Infection Increases EBV-Associated Tumor Formation In Vivo via
Enhanced EBV Lytic Gene Expression.
AB - The human tumor viruses Epstein-Barr virus (EBV) and Kaposi sarcoma-associated
herpesvirus (KSHV) establish persistent infections in B cells. KSHV is linked to
primary effusion lymphoma (PEL), and 90% of PELs also contain EBV. Studies on
persistent KSHV infection in vivo and the role of EBV co-infection in PEL
development have been hampered by the absence of small animal models. We
developed mice reconstituted with human immune system components as a model for
KSHV infection and find that EBV/KSHV dual infection enhanced KSHV persistence
and tumorigenesis. Dual-infected cells displayed a plasma cell-like gene
expression pattern similar to PELs. KSHV persisted in EBV-transformed B cells and
was associated with lytic EBV gene expression, resulting in increased tumor
formation. Evidence of elevated lytic EBV replication was also found in EBV/KSHV
dually infected lymphoproliferative disorders in humans. Our data suggest that
KSHV augments EBV-associated tumorigenesis via stimulation of lytic EBV
replication.
PMID- 28704655
TI - War on Viruses: LC3 Recruits GTPases.
AB - Interferon effector functions and autophagy are evolutionarily conserved arms of
cell-autonomous immunity that restrict replication of intracellular pathogens. In
this issue of Cell Host and Microbe, Biering et al., (2017) demonstrate how host
cells co-opt sequential action of autophagy proteins and IFN-inducible GTPases to
inhibit replication of positive-sense RNA viruses.
PMID- 28704656
TI - Induction of INKIT by Viral Infection Negatively Regulates Antiviral Responses
through Inhibiting Phosphorylation of p65 and IRF3.
AB - The transcription factors p65 and IRF3 play key roles in the induction of
cellular antiviral responses. Phosphorylation of p65 and IRF3 is required for
their activity and constitutes a key checkpoint. Here we report that viral
infection induced upregulation of INKIT, an inhibitor for NF-kappaB and IRF3 that
restricted innate antiviral responses by blocking phosphorylation of p65 and
IRF3. INKIT overexpression inhibited virus-induced phosphorylation of p65 and
IRF3 and expression of downstream genes. In contrast, knockdown or knockout of
INKIT had the opposite effect: Inkit-/- mice produced elevated levels of type I
interferons and proinflammatory cytokines and were more resistant to lethal viral
infection compared to wild-type. INKIT interacted with IKKalpha/beta and
TBK1/IKKE, impairing the recruitment and phosphorylation of p65 and IRF3. Viral
infection induced IKK-mediated phosphorylation of INKIT at Ser58, resulting in
its dissociation from the IKKs. Our findings thus uncover INKIT as a regulator of
innate antiviral responses.
PMID- 28704657
TI - Dual Blades: The Role of Musashi 1 in Zika Replication and Microcephaly.
AB - Infection with Zika virus (ZIKV) during pregnancy may cause severe developmental
defects in the human brain via unknown mechanisms. In a recent issue of Science,
Chavali et al. (2017) identified a neural progenitor cell (NPC)-specific RNA
binding protein that may underlie the high levels of ZIKV replication and
apoptosis observed in these cells during congenital infections.
PMID- 28704659
TI - Preheating mitigates cadmium toxicity in zebrafish livers: Evidence from promoter
demethylation, gene transcription to biochemical levels.
AB - The working hypothesis for this study was that moderate heat stress would
alleviate the deleterious effects of subsequent cadmium (Cd) exposure on fish.
Thus, zebrafish (Danio rerio) were subjected to water maintained at 26 degrees C
and 34 degrees C for 4days, and then exposed to 0 or 200MUg/L Cd for 1 week at 26
degrees C. Multiple indicators were measured from livers of zebrafish at
different levels, including DNA, RNA, protein and enzymatic activity associated
with oxidative stress, inflammation and metal transport. The ameliorative effect
of preheatinging on Cd toxicity was demonstrated. In the Cd-exposed groups,
preheating decreased mortality and lipid peroxidation, increased activity levels
of catalase (CAT) and copper/zinc-superoxide dismutase (Cu/Zn-SOD), and up
regulated mRNA levels of heat shock protein 70 (HSP70) and heat shock factor 2
(HSF2). Preheating also mitigated Cd-induced increases in protein and mRNA levels
of metallothioneins (MTs), and mRNA levels of several inflammation-related genes.
Furthermore, preheating alone dramatically up-regulated mRNA levels of genes
related to antioxidant and immune defenses, zinc and copper transporters, protein
folding, and reduced methylation levels in the HSF binding motif of the HSP70
promoter. Overall, preheating-induced accumulation of transcripts via
demethylation might support the rapid defense responses at post-transcriptional
levels caused by subsequent Cd exposure, indicating an adaptive mechanism for
organisms exposed to one mild stressor followed by another.
PMID- 28704658
TI - Fusion Stage of HIV-1 Entry Depends on Virus-Induced Cell Surface Exposure of
Phosphatidylserine.
AB - HIV-1 entry into host cells starts with interactions between the viral envelope
glycoprotein (Env) and cellular CD4 receptors and coreceptors. Previous work has
suggested that efficient HIV entry also depends on intracellular signaling, but
this remains controversial. Here we report that formation of the pre-fusion Env
CD4-coreceptor complexes triggers non-apoptotic cell surface exposure of the
membrane lipid phosphatidylserine (PS). HIV-1-induced PS redistribution depends
on Ca2+ signaling triggered by Env-coreceptor interactions and involves the lipid
scramblase TMEM16F. Externalized PS strongly promotes Env-mediated membrane
fusion and HIV-1 infection. Blocking externalized PS or suppressing TMEM16F
inhibited Env-mediated fusion. Exogenously added PS promoted fusion, with fusion
dependence on PS being especially strong for cells with low surface density of
coreceptors. These findings suggest that cell-surface PS acts as an important
cofactor that promotes the fusogenic restructuring of pre-fusion complexes and
likely focuses the infection on cells conducive to PS signaling.
PMID- 28704660
TI - Pathway analysis of systemic transcriptome responses to injected polystyrene
particles in zebrafish larvae.
AB - Microplastics are a contaminant of emergent concern in the environment, however,
to date there is a limited understanding on their movement within organisms and
the response of organisms. In the current study zebrafish embryos at different
development stages were exposed to 700nm fluorescent polystyrene (PS) particles
and the response pathway after exposure was investigated using imaging and
transcriptomics. Our results show limited spreading of particles within the
larvae after injection during the blastula stage. This is in contrast to
injection of PS particles in the yolk of 2-day old embryos, which resulted in
redistribution of the PS particles throughout the bloodstream, and accumulation
in the heart region. Although injection was local, the transcriptome profiling
showed strong responses of zebrafish embryos exposed to PS particle, indicating a
systemic response. We found several biological pathways activated which are
related to an immune response in the PS exposed zebrafish larvae. Most notably
the complement system was enriched as indicated by upregulation of genes in the
alternative complement pathway (e.g. cfhl3, cfhl4, cfb and c9). The fact that
complement pathway is activated indicates that plastic microparticles are
integrated in immunological recognition processes. This was supported by
fluorescence microscopy results, in which we observed co-localisation of
neutrophils and macrophages around the PS particles. Identifying these key events
can be a first building block to the development of an adverse outcome pathway
(AOP). These data subsequently can be used within ecological and human risk
assessment.
PMID- 28704661
TI - Direct and indirect photolysis of seven micropollutants in secondary effluent
from a wastewater lagoon.
AB - The photodegradation of seven micropollutants commonly found in municipal
wastewater, namely caffeine, carbamazepine, diuron, simazine, sulfamethoxazole,
triclosan and 2,4-D, was investigated in pure water and secondary effluent to
understand the direct and indirect photolysis of these compounds under natural
sunlight irradiation. Sulfamethoxazole and triclosan were readily photodegraded
with half-lives of 5.8 and 1.8 h, respectively, whilst the others were relatively
resistant towards sunlight irradiation. Enhanced degradation was observed in
secondary effluent compared with in the pure water matrix for all compounds,
except for triclosan. It was confirmed that hydroxyl radicals played an important
role in the photodegradation of the micropollutants while singlet oxygen may also
play a role. The contribution of hydroxyl radical to the overall degradation of
the five compounds that were resistant to direct sunlight accounted for 32%-70%.
The impact of humic acid and nitrate, two known photosensitisers and wastewater
components, on the photodegradation of the seven micropollutants in pure water
was investigated under simulated solar radiation. The presence of nitrate
promoted the photochemical loss of all seven micropollutants, however, humic acid
caused promotion or inhibition, depending on the characteristics of the
micropollutant. Humic acid enhanced the photolytic degradation of caffeine,
sulfamethoxazole and diuron, while it hindered the photodegradation of the other
four compounds by absorbing the available irradiation energy and/or reforming the
parent compound. Furthermore, it was shown that there was only a small increase
(up to 15%) in photodegradation of the compounds at 25 degrees C compared with
that at 10 degrees C in the simulated system.
PMID- 28704662
TI - Assessment of heavy metal contamination in sediment at Sukinda ultramafic complex
using HAADF-STEM analysis.
AB - The Sukinda ultramafic complex in Odisha has the largest chromite reserve in
India. Sediment derived from ultramafic rocks has been enriched with various
metals. Further, mining activities enhance the influx of metals into sediment by
dumping mine overburden and tailings in the open area. Metal concentration in
sediment is found in order of CrTotal(Cr) > Mn > Ni > Co > Zn > Cu with average
concentration 26,778 mg/kg, 3098 mg/kg, 1813 mg/kg, 184 mg/kg, 116 mg/kg and 44
mg/kg respectively. Concentration of Cr(VI) varies from 5.25 to 26.47 mg/L with
an average of 12.27 mg/L. Based on various pollution indices, it is confirmed
that the area is severely contaminated. Nano-scale goethite, kaolinite,
clinochlore and chromite have been identified and have high concentration of Cr,
Co and Ni. Goethite has shown maximum metal retention potential as deciphered by
high-angle annular dark-field scanning transmission electron microscopy (HAADF
STEM). The HAADF-STEM mapping and principal component analysis indicate that Cr
and Co mostly derived from chromite whereas Ni and Zn are derived from
serpentine. Later, these metals co-precipitate and/or adsorbed onto the goethite
and clay minerals. Fractionation study of metals confirms that Cu is the most
mobile element followed by Zn. However, at low pH condition Ni is mobilized and
likely to be bioavailable. Though Cr mostly occurs in residual fraction but as
its concentration is very high, a small proportion of exchangeable fraction
contributes significantly in terms of its bioavailability. Thus bioavailable Cr
can pose severe threat to the environment in the Sukinda ultramafic complex.
PMID- 28704663
TI - Effect of sulfide on As(III) and As(V) sequestration by ferrihydrite.
AB - The sulfide-induced change in arsenic speciation is often coupled to iron
geochemical processes, including redox reaction, adsorption/desorption and
precipitation/dissolution. Knowledge about how sulfide influenced the coupled
geochemistry of iron and arsenic was not explored well up to now. In this work,
retention and mobilization of As(III) and As(V) on ferrihydrite in sulfide-rich
environment was studied. The initial oxidation states of arsenic and the contact
order of sulfide notably influenced arsenic sequestration on ferrihydrite. For
As(III) systems, pre-sulfidation of As(III) decreased arsenic sequestration
mostly. The arsenic adsorption capacity decreased about 50% in comparison with
the system without sulfide addition. For As(V) systems, pre-sulfidation of
ferrihydrite decreased 30% sequestration of arsenic on ferrihydrite. Reduction of
ferrihydrite by sulfide in As(V) system was higher than that in As(III) system.
Geochemical modeling calculations identified formation of thioarsenite in the pre
sulfidation of As(III) system. Formation of arsenic thioanions enhanced As
solubility in the pre-sulfidation of As(III) system. The high concentration of
sulfide and Fe(II) in pre-sulfidation of ferrihydrite system contributed to
saturation of FeS. This supplied new solid phase to immobilize soluble arsenic in
aqueous phase. X-ray absorption near edge spectroscopy (XANES) of sulfur K-edge,
arsenic K-edge and iron L-edge analysis gave the consistent evidence for the
sulfidation reaction of arsenic and ferrihydrite under specific geochemical
settings.
PMID- 28704664
TI - A primary estimation of PCDD/Fs release reduction from non-wood pulp and paper
industry in China based on the investigation of pulp bleaching with chlorine
converting to chlorine dioxide.
AB - Chlorine bleaching technology (C process, CEH process, H process and theirs
combination), which was identified as a primary formation source of PCDD/Fs, is
still widely used by the vast majority of Chinese non-wood pulp and paper mills
(non-wood PMs). The purpose of this study was to provide information and data
support for further eliminating dioxin for non-wood PMs in China, and especially
to evaluate the PCDD/Fs release reduction for those mills converting their pulp
bleaching processes from CEH to ECF. The PCDD/Fs concentrations of the bleached
pulp and bleaching wastewater with ECF bleaching were in the ranges of 0.13-0.8
ng TEQ kg-1, and 0.15-1.9 pg TEQ L-1, respectively, which were far lower than
those with CEH process, indicating that the ECF process is an effective
alternative bleaching technology to replace CEH in Chinese non-wood PMs to reduce
dioxin release. The release factor via flue gas of the alkali recovery boiler in
Chinese non-wood PMs was first reported to be 0.092 MUg TEQ Ad t-1 in this study.
On the assumption that pulp bleaching processes of all Chinese non-wood PMs were
converted from CEH to ECF, the annual release of PCDD/Fs via the bleaching
wastewater and bleached pulp would be reduced by 79.1%, with a total of 1.60 g
TEQ.
PMID- 28704665
TI - Effect of temperature on N2O emissions from a highly enriched nitrifying granular
sludge performing partial nitritation of a low-strength wastewater.
AB - In the race to achieve a sustainable urban wastewater treatment plant, not only
the energy requirements have to be considered but also the environmental impact
of the facility. Thus, nitrous oxide (N2O) emissions are a key-factor to pay
attention to, since they can dominate the total greenhouse gases emissions from
biological wastewater treatment. In this study, N2O production factors were
calculated during the operation of a granular sludge airlift reactor performing
partial nitritation treating a low-strength synthetic influent, and furthermore,
the effect of temperature on N2O production was assessed. Average gas emission
relative to conversion of ammonium was 1.5 +/- 0.3% and 3.7 +/- 0.5% while the
effluent contained 0.5 +/- 0.1% and 0.7 +/- 0.1% (% N-oxidized) at 10 and 20
degrees C, respectively. Hence, temperature increase resulted in higher N2O
production. The reasons why high temperature favoured N2O production remained
unclear, but different theoretical hypotheses were suggested.
PMID- 28704666
TI - TiO2 supported on reed straw biochar as an adsorptive and photocatalytic
composite for the efficient degradation of sulfamethoxazole in aqueous matrices.
AB - Heterogeneous photocatalysis namely titanium dioxide supported on reed straw
biochar (acid pre-treated) (TiO2/pBC) was synthesized by sol-gel method. The
morphology, surface area and structure of TiO2/pBC were characterized by scanning
electron microscopy (SEM), Brunauer-Emmett-Teller (BET), and X-ray diffraction
(XRD). Low calcination condition maintained the structure of biochar completely
and prevented the agglomeration of TiO2 particles. Due to the combination of
adsorption and photocatalysis, TiO2/pBC performed higher removal efficiency of
sulfamethoxazole (SMX) than pure TiO2 powder under UV light irradiation. The
photocatalytic degradation (PCD) of SMX was also studied with the water collected
from the Yellow River. Three high concentration inorganic anions (Cl-, NO3-, SO42
) of the river exerted certain degree of detrimental effects on the contaminant
degradation. TiO2/pBC showed stable photocatalytic activity after five sequential
PCD cycles. The biochar was able to promote further PCD on TiO2 by adsorbing SMX
and intermediates thereby prolonging the separation lifetime of electrons (e-)
and valence band hole (h+). The transformation intermediates of SMX were
identified and three possible degradation reactions of hydroxylation, opening of
isoxazole ring and cleavage of SN bond might occur during the PCD of SMX.
PMID- 28704667
TI - Occurrence and temporal variation of antibiotic resistance genes (ARGs) in shrimp
aquaculture: ARGs dissemination from farming source to reared organisms.
AB - Considerable attention has been paid to the occurrence and abundance of
antibiotic resistance genes (ARGs) in aquatic environments. However, the temporal
variation and dissemination of ARGs in aquaculture environments and reared
organisms need further study. This study investigated the abundance and diversity
of ARGs and bacterial community in water source, shrimp pond water, sediment, and
shrimps during the rearing period in Pearl River Delta region, South China. The
results showed that sul1, qnrD, cmlA, and floR were the predominant ARGs in the
aquaculture samples. A trend of decreasing abundance of ARGs was observed for
pond water samples during the rearing period, whereas an increasing trend was
observed in the sediment and shrimp samples. The total concentration of ARGs in
water source was significantly higher than that in shrimp pond water (p<0.05). A
significant negative correlation was found between the total concentrations of
ARGs in pond waters and sediments (p<0.01). The total abundances of ARGs in
intestinal tract of adult shrimps were 4.48-19.0 times higher than those in
juvenile shrimps. Similar to water source and pond water, cmlA and sul1 were the
predominant ARGs in shrimp intestinal tract. The bacterial community in the
shrimp intestinal tract changed greatly from juvenile to adult. The results of
the present study indicated that the abundances of ARGs in aquaculture varied
temporally during the rearing period. Water source was an important medium
disseminating ARGs to the aquaculture environments and reared organisms. Sul1
could be used as a potential indicator for ARGs in both water and sediment in
aquaculture in the estuary of the Pearl River Delta, South China. This study
represents a case study for the temporal variation of abundance and dissemination
of ARGs in aquaculture and is a reference for potential risks to food safety and
human health.
PMID- 28704668
TI - Performance and implementation of low impact development - A review.
AB - Climate change, urbanization, and ecological concerns are all driving the need
for new stormwater management strategies. The effects of urbanization are
exaggerated by climate change and thus the development of innovative stormwater
management techniques are necessary to mitigate these impacts. One emerging
stormwater management philosophy is low impact development (LID). LID utilizes
distributed stormwater controls (often green infrastructure) as well as green
spaces and natural hydrologic features in order to bring the hydrology of urban
catchments closer to pre-development conditions. The review provides a summary of
the knowledge of LID as a stormwater management technique and climate change
mitigation measure as well as the current state of research and implementation of
this topic. In order to provide a better understanding of the extensive scope
that should be considered for design of low impact developments, methods of
optimization, modelling, monitoring and the performance of LID alternatives is
covered. LID has been widely adopted and proven successful in many cases;
however, there remains uncertainty of its benefits. This review brings together
knowledge from many sources in order to provide an overview of LID and examine
its performance and implementation.
PMID- 28704669
TI - Coupling life-cycle assessment and the RothC model to estimate the carbon
footprint of green manure-based wheat production in China.
AB - Reducing the carbon footprint (CF) of crop production is an efficient way to
mitigate climate change. Growing legume green manure (LGM) instead of summer
fallow may achieve this goal by lowering synthetic nitrogen (N) fertilizer needs
and replenishing the depleted soil carbon (C) pool. The Rothamsted Carbon (RothC)
model was incorporated into the Life-Cycle Assessment (LCA) to evaluate the
present and projected CFs of green manure-based wheat production systems in
dryland agriculture on the Loess Plateau of China. The field study included four
main treatments (Huai bean, soybean and mung bean grown as green manure in summer
and fallow as control) and four synthetic N rates (0, 108, 135 and 162kgNha-1)
applied at wheat sowing. Soybean as LGM increased averaged wheat yield over 4
synthetic N rates by 8% compared with fallow (P<0.05), and synthetic N
requirement was reduced by 33% without compromising the wheat yield for all the
main treatments. Although LGM treatments had higher greenhouse gas (GHG)
emissions from agricultural inputs, the greater amount of C inputs elevated the
corresponding SOC stocks (SOCS) by 14-24% after 8years, thus significantly
reducing the CF by 25-51% compared with fallow. The modelled SOCS equilibrium
indicates that the CF for cropping systems with LGM will be 53-62% lower than
fallow and 23-37% lower compared with their current level. In conclusion,
introducing legume green manure instead of summer fallow is a highly efficient
measure for persistent CF reduction, and coupling the RothC model and LCA is an
alternative method to predict the long-term impact of different cropping systems
on GHG emissions.
PMID- 28704670
TI - Cryo-conditioned rocky coast systems: A case study from Wilczekodden, Svalbard.
AB - This paper presents the results of an investigation into the processes
controlling development of a cryo-conditioned rock coast system in Hornsund,
Svalbard. A suite of nested geomorphological and geophysical methods have been
applied to characterise the functioning of rock cliffs and shore platforms
influenced by lithological control and geomorphic processes driven by polar coast
environments. Electrical resistivity tomography (ERT) surveys have been used to
investigate permafrost control on rock coast dynamics and reveal the strong
interaction with marine processes in High Arctic coastal settings. Schmidt hammer
rock tests, demonstrated strong spatial control on the degree of rock weathering
(rock strength) along High Arctic rock coasts. Elevation controlled geomorphic
zones are identified and linked to distinct processes and mechanisms,
transitioning from peak hardness values at the ice foot through the wave and
storm dominated scour zones to the lowest values on the cliff tops, where the
effects of periglacial weathering dominate. Observations of rock surface change
using a traversing micro-erosion meter (TMEM) indicate that significant changes
in erosion rates occur at the junction between the shore platform and the cliff
toe, where rock erosion is facilitated by frequent wetting and drying and
operation of nivation and sea ice processes (formation and melting of snow
patches and icefoot complexes). The results are synthesised to propose a new
conceptual model of High Arctic rock coast systems, with the aim of contributing
towards a unifying concept of cold region landscape evolution and providing
direction for future research regarding the state of polar rock coasts.
PMID- 28704671
TI - Long-term cultivation of Bt rice expressing the Cry1Ab/1Ac gene reduced
phytoparasitic nematode abundance but did not affect other nematode parameters in
paddy fields.
AB - The uncertainty of ecological risks and the effects of growing transgenic Bt rice
on the environment hamper its commercial production. Here, soil nematode
communities were used as an indicator of soil health and soil food web structure
to evaluate the potential effects of growing Bt rice without chemical
insecticides for 3years in the paddy field. The nematodes and soil
physicochemical properties of Bt rice fields were compared to the near-isogenic
control, non-Bt rice fields. A total of 108,363 specimens belonging to 28
different genera were enumerated. The Hirschmanniella, Tobrilus, Dorylaimus and
Filenchus were dominant genera. A three-year paddy rice cultivation of Bt rice
(Huahui 1) negatively affected the abundance of phytoparasitic nematodes but did
not affect the total number of nematodes, the abundance and relative abundance of
free-living nematodes, genera richness, diversity indices, soil food web
conditions, or community compositions. However, apparent seasonal and inter
annual changes in these variables were observed, indicating that the impact of
environmental factors was more stronger than that of the Bt toxin. In conclusion,
the potential ecological risks of Bt rice on soil health and sustainability
warrant further research to disentangle the impacts from various confounding
environmental factors.
PMID- 28704673
TI - Contributions of combined sewer overflows and treated effluents to the bacterial
load released into a coastal area.
AB - The impact of combined sewer overflow (CSO) on the receiving water body is an
issue of increasing concern, as it may lead to restrictions in the use and
destination of the receiving body, such as bathing or recreational area closures,
fish and shellfish consumption restrictions, and contamination of drinking water
resources. Recent investigations have mainly referred to the occurrence and loads
of suspended solids, organic compounds and, in some cases, micropollutants.
Attempts have been made to find correlations between the discharged load and the
size and characteristics of the catchment area, climate conditions, rainfall
duration and intensity. This study refers to a touristic coastal area in the
north-east of Italy, which is characterized by a combined sewer network including
5 CSO outfalls which, in the case of heavy rain events, directly discharge the
exceeding water flow rate into channels which, after a short distance, reach the
Adriatic Sea. The study analyzed: i) rainfall events during the summer period in
2014 which led to overflow in the different outfalls, ii) the inter- and intra
event variability with regard to E. coli, Enterococci and conductivity, and iii)
the hydraulic and pollutant (E. coli and Enterococci) loads discharged by the
local wastewater treatment plant and by all the CSO outfalls. Finally, it
estimated the contribution of each source to the released hydraulic and pollutant
loads into the receiving water body. Moreover, it was also found that the modest
water volume discharged by all CSO outfalls (only 8% of the total volume
discharged by the area) contains >90% of the microbial load.
PMID- 28704672
TI - Anthropometric measures at birth and early childhood are associated with
neurodevelopmental outcomes among Bangladeshi children aged 2-3years.
AB - Among a cohort of children located in rural areas of Bangladesh affected by high
levels of exposure to environmental metals, we investigated the associations
between anthropometric measures, growth trajectory, and neurodevelopment at age
20-40months. Our study population included mothers and their children who
participated in a longitudinal birth cohort study that took in place in the Pabna
and Sirajdikhan areas of Bangladesh. Anthropometric measures including weight,
length, and head circumference were measured at birth, age 12months, and age 20
40months. Neurodevelopment was assessed using Bayley Scales of Infant and Toddler
Development Third Edition (BSID-III) multi-scale at age 20-40months. A total of
777 mother-child pairs were included. Higher anthropometric measures at 20
40months were associated with higher cognitive, language, and motor scores on
BSID-III. For example, a 1-kg increment in birthweight was associated with an
increase of 2.11 for cognitive score (p<0.0001), 1.63 for language score
(p=0.006), and 0.89 for motor scores (p=0.03). Greater positive changes in growth
parameters, or growth trajectory, between birth and 20-40months were also
associated with higher BSID-III scores. These associations remained significant
after adjusting for potential confounders and prenatal exposure to environmental
metals. These findings suggest that even when taking into account high
environmental metal exposures, prenatal and early childhood growth have strong
associations with neurodevelopmental test scores in early childhood.
PMID- 28704674
TI - Urban growth and water access in sub-Saharan Africa: Progress, challenges, and
emerging research directions.
AB - For the next decade, the global water crisis remains the risk of highest concern,
and ranks ahead of climate change, extreme weather events, food crises and social
instability. Across the globe, nearly one in ten people is without access to an
improved drinking water source. Least Developed Countries (LDCs) especially in
sub-Saharan Africa (SSA) are the most affected, having disproportionately more of
the global population without access to clean water than other major regions.
Population growth, changing lifestyles, increasing pollution and accelerating
urbanization will continue to widen the gap between the demand for water and
available supply especially in urban areas, and disproportionately affect
informal settlements, where the majority of SSA's urban population resides.
Distribution and allocation of water will be affected by climate-induced water
stresses, poor institutions, ineffective governance, and weak political will to
address scarcity and mediate uncertainties in future supply. While attempts have
been made by many scientists to examine different dimensions of water scarcity
and urban population dynamics, there are few comprehensive reviews, especially
focused on the particular situation in Sub-Saharan Africa. This paper contributes
to interdisciplinary understanding of urban water supply by distilling and
integrating relevant empirical knowledge on urban dynamics and water issues in
SSA, focusing on progress made and associated challenges. It then points out
future research directions including the need to understand how alternatives to
centralized water policies may help deliver sustainable water supply to cities
and informal settlements in the region.
PMID- 28704675
TI - Effect of single-wall carbon nanotubes on bioconcentration and toxicity of
perfluorooctane sulfonate in zebrafish (Danio rerio).
AB - The wide application of nanoparticles will lead its release into the aquatic
environment, which may alter the bioavailability and toxicity of other
contaminants to aquatic organisms. This work aimed to study the effects of
perfluorooctane sulfonate (PFOS), single-wall carbon nanotubes (SWCNT), and their
mixture on PFOS accumulation, antioxidant defenses and acetylcholinesterase
(AChE) activity in zebrafish. The fish was dissected after being exposed (24, 48,
72 and 96h) separately to PFOS, SWCNT and PFOS+SWCNT co-exposure. The
bioaccumulation of PFOS in fish tissues (liver, intestines, gills and brain)
decreased with increasing dosage of SWCNT, however, the opposite trend was
observed in fish skin, which indicated that the bioavailability of PFOS changed
by adsorption on SWCNT. Meanwhile, co-exposure induced more reactive oxygen
species (ROS) than PFOS alone and enhanced the effect of PFOS on the superoxide
dismutase (SOD), and catalase (CAT) and AChE activities. Furthermore, the
integrated biomarker response (IBR) showed that co-exposure was the most
stressful circumstance.
PMID- 28704676
TI - TREHS: An open-access software tool for investigating and evaluating temporary
river regimes as a first step for their ecological status assessment.
AB - When the regime of a river is not perennial, there are four main difficulties
with the use of hydrographs for assessing hydrological alteration: i) the main
hydrological features relevant for biological communities are not quantitative
(discharges) but qualitative (phases such as flowing water, stagnant pools or
lack of surface water), ii) stream flow records do not inform on the temporal
occurrence of stagnant pools, iii) as most of the temporary streams are ungauged,
their regime has to be evaluated by alternative methods such as remote sensing or
citizen science, and iv) the biological quality assessment of the ecological
status of a temporary stream must follow a sampling schedule and references
adapted to the flow- pool-dry regime. To overcome these challenges within an
operational approach, the freely available software tool TREHS has been developed
within the EU LIFE TRIVERS project. This software permits the input of
information from flow simulations obtained with any rainfall-runoff model (to set
an unimpacted reference stream regime) and compares this with the information
obtained from flow gauging records (if available) and interviews with local
people, as well as instantaneous observations by individuals and interpretation
of ground-level or aerial photographs. Up to six metrics defining the permanence
of water flow, the presence of stagnant pools and their temporal patterns of
occurrence are used to determine natural and observed river regimes and to assess
the degree of hydrological alteration. A new regime classification specifically
designed for temporary rivers was developed using the metrics that measure the
relative permanence of the three main phases: flow, disconnected pools and dry
stream bed. Finally, the software characterizes the differences between the
natural and actual regimes, diagnoses the hydrological status (degree of
hydrological alteration), assesses the significance and robustness of the
diagnosis and recommends the best periods for biological quality samplings.
PMID- 28704677
TI - Hydrated electron based decomposition of perfluorooctane sulfonate (PFOS) in the
VUV/sulfite system.
AB - As one of the most reactive species, hydrated electron (eaq-) is promising for
reductive decomposition of recalcitrant organic pollutants, such as
perfluorooctane sulfonate (PFOS). In this study, PFOS decomposition using a
vacuum ultraviolet (VUV)/sulfite system was systematically investigated in
comparison with sole VUV and ultraviolet (UV)/sulfite systems. A fast and nearly
complete (97.3%) PFOS decomposition was observed within 4h from its initial
concentration of 37.2MUM in the VUV/sulfite system. The observed rate constant
(kobs) for PFOS decomposition in the studied system was 0.87+/-0.0060h-1, which
was nearly 7.5 and 2 folds faster than that in sole VUV and UV/sulfite systems,
respectively. Compared to previously studied UV/sulfite system, VUV/sulfite
system enhanced PFOS decomposition in both weak acidic and alkaline pH
conditions. In weak acidic condition (pH6.0), PFOS predominantly decomposed via
direct VUV photolysis, whereas in alkaline condition (pH>9.0), PFOS decomposition
was mainly induced by eaq- generated from both sulfite and VUV photolytic
reactions. At a fixed initial solution pH (pH10.0), PFOS decomposition kinetics
showed a positive linear dependence with sulfite dosage. The co-presence of humic
acid (HA) and NO3- obviously suppressed PFOS decomposition, whereas HCO3- showed
marginal inhibition. A few amount of short chain perfluorocarboxylic acids
(PFCAs) were detected in PFOS decomposition process, and a high defluorination
efficiency (75.4%) was achieved. These results suggested most fluorine atoms in
PFOS molecule ultimately mineralized into fluoride ions, and the mechanisms for
PFOS decomposition in the VUV/sulfite system were proposed.
PMID- 28704678
TI - The role of microbial diversity and composition in minimizing sludge production
in the oxic-settling-anoxic process.
AB - The oxic-settling-anoxic (OSA) process, which involves an aerobic tank attached
to oxygen- and substrate-deficient external anoxic reactors, minimizes sludge
production in biological wastewater treatment. In this study, the microbial
community structure of OSA was determined. Principal coordinate analysis showed
that among the three operational factors, i.e., (i) redox condition, (ii)
external reactor sludge retention time (SRText), and (iii) sludge interchange
between aerobic and anoxic reactors, redox condition had the greatest impact on
microbial diversity. Generally, reactors with lower oxidation-reduction potential
had higher microbial diversity. The main aerobic sequencing batch reactor of OSA
(SBROSA) that interchanged sludge with an external anoxic reactor had greater
microbial diversity than SBRcontrol which did not have sludge interchange. SBROSA
sustained high abundance of the slow-growing nitrifying bacteria (e.g.,
Nitrospirales and Nitrosomondales) and consequently exhibited reduced sludge
yield. Specific groups of bacteria facilitated sludge autolysis in the external
reactors. Hydrolyzing (e.g., Bacteroidetes and Chloroflexi) and fermentative
(e.g., Firmicutes) bacteria, which can break down cellular matter, proliferated
in both the external aerobic/anoxic and anoxic reactors. Sludge autolysis in the
anoxic reactor was enhanced with the increase of predatory bacteria (e.g., order
Myxobacteriales and genus Bdellovibrio) that can contribute to biomass decay.
Furthermore, beta- and gamma-Proteobacteria were identified as the bacterial
phyla that primarily underwent decay in the external reactors.
PMID- 28704679
TI - pH-sensitive polymer-modified liposome-based immunity-inducing system: Effects of
inclusion of cationic lipid and CpG-DNA.
AB - Efficient vaccine carriers for cancer immunotherapy require two functions:
antigen delivery to dendritic cells (DCs) and the activation of DCs, a so-called
adjuvant effect. We previously reported antigen delivery system using liposomes
modified with pH-sensitive polymers, such as 3-methylglutarylated hyperbranched
poly(glycidol) (MGlu-HPG), for the induction of antigen-specific immune
responses. We reported that inclusion of cationic lipids to MGlu-HPG-modified
liposomes activates DCs and enhances antitumor effects. In this study, CpG-DNA, a
ligand to Toll-like receptor 9 (TLR9) expressing in endosomes of DCs, was
introduced to MGlu-HPG-modified liposomes containing cationic lipids using two
complexation methods (Pre-mix and Post-mix) for additional activation of antigen
specific immunity. For Pre-mix, thin membrane of lipids and polymers were
dispersed by a mixture of antigen/CpG-DNA. For Post-mix, CpG-DNA was added to pre
formed liposomes. Both Pre-mix and Post-mix delivered CpG-DNA to DC endosomes,
where TLR9 is expressing, more efficiently than free CpG-DNA solution did. These
liposomes promoted cytokine production from DCs and the expression of co
stimulatory molecules in vitro and induced antigen-specific immune responses in
vivo. Both Pre-mix and Post-mix exhibited strong antitumor effects compared with
conventional pH-sensitive polymer-modified liposomes. Results show that inclusion
of multiple adjuvant molecules into pH-sensitive polymer-modified liposomes and
suitable CpG-DNA complexation methods are important to design potent vaccine
carriers.
PMID- 28704680
TI - Differentiating parotid tumors by quantitative signal intensity evaluation on MR
imaging.
AB - BACKGROUND: There have been no reports about quantitative evaluations of
enhancing components of parotid tumors on conventional MR imaging. PURPOSE: To
evaluate the signal intensity of the enhancing components of tumors, including
pleomorphic adenomas (PAs), Warthin tumors (WTs) and malignant tumors (MTs), on
various MR sequences and to assess the usefulness of quantitative evaluations for
differentiation among the three groups of tumors. MATERIAL AND METHODS: A total
of 39 histologically proven tumors, including 15 PAs, 17 WTs and 7 MTs, were
enrolled in this study. The tumor-to-spinal cord contrast ratio (TSc-CR) was
calculated by dividing the signal intensity of the lesion by that of the spinal
cord on MR sequences, including T1-weighted imaging (T1WI), T2-weighted imaging
(T2WI) and postcontrast gadolinium-enhanced T1WI (CE-T1WI). The mean apparent
diffusion coefficient (ADC) value was selected in each tumor. Furthermore, the
differences in the TSc-CRs and the ADC values among the three groups of tumors
were statistically evaluated. Cutoff values were determined for the prediction of
tumor histology. RESULTS: The TSc-CRs of PAs were significantly higher than those
of WTs and MTs on T2WI and CE-T1WI. The sensitivities and specificities were 100%
and 87.5%, respectively, at a cutoff value of 1.31 for the TSc-CR of T2WI; and
83.3% and 100%, respectively, at a cutoff value of 2.00 for the TSc-CR of CE
T1WI. For the ADC values, sensitivity and specificity for discriminating PAs from
WTs or MTs were both 100% when the cutoff value of the ADC was set at 1.40*10
3mm2/s. CONCLUSION: ADC maps and the quantitative evaluations using the TSc-CRs
on T2WI and CE-T1WI were useful for discriminating WTs or MTs from PAs. However,
discrimination between WTs and MTs was difficult using any MR sequence.
PMID- 28704681
TI - Cytokine IL1alpha and lactate as markers for tissue damage in spineboard
immobilisation. A prospective, randomised open-label crossover trial.
AB - BACKGROUND: Spinal immobilisation using a rigid long spineboard is a well
established procedure in trauma care. During immobilisation, the body is exposed
to high tissue-interface pressures. This may lead to a localised inflammatory
response of the skin, which may be used to monitor the body's response to
different types of immobilisation device. AIM: In this study we compared the
standard rigid spineboard with a new soft-layered spineboard regarding tissue
interface pressures, skin redness as an indicator of reactive hyperaemia and
cutaneous IL1alpha and lactate release. METHODS: Twelve healthy male participants
were asked to lie supine on both a rigid and a soft-layered spineboard, loading
the sacrum for one hour, followed by one hour in unloaded position. Tissue
interface pressures on the buttocks during loading were measured continuously
using a pressure mapping mat. Cutaneous IL1alpha and lactate concentrations were
assessed using Sebutapes, during 20-min periods. After each 20-min period, a
photo of the buttocks was taken, which was later assessed for redness by two
observers. RESULTS: Significant differences in tissue-interface pressure and
reactive hyperaemia were found between the two types of spineboard. Release of
IL1alpha and lactate were found to increase with prolonged exposure to pressure,
and to decrease in the unloaded prone position. A significant relationship was
found between tissue-interface pressure and reactive hyperaemia, but not with
IL1alpha nor lactate release. Time course of IL1alpha and lactate release was
similar for both types of spineboard. CONCLUSIONS: IL1alpha and lactate both have
a strong relationship with pressure exposure time, but not with pressure
magnitude. Furthermore, IL1alpha was measured even in the absence of visible
redness of the skin. The study offers the potention of biomarkers, reflecting
inflammation and/or tissue metabolism, for use in assessing the effects of
prolonged spineboard support.
PMID- 28704682
TI - Mutagenic potential of hypoxanthine in live human cells.
AB - Hypoxanthine (Hx) is a major DNA lesion generated by deamination of adenine
during chronic inflammatory conditions, which is an underlying cause of various
diseases including cancer of colon, liver, pancreas, bladder and stomach. There
is evidence that deamination of DNA bases induces mutations, but no study has
directly linked Hx accumulation to mutagenesis and strand-specific mutations yet
in human cells. Using a site-specific mutagenesis approach, we report the first
direct evidence of mutation potential and pattern of Hx in live human cells. We
investigated Hx-induced mutations in human nonmalignant HEK293 and cancer HCT116
cell lines and found that Hx is mutagenic in both HEK293 and HCT116 cell lines.
There is a strand bias for Hx-mediated mutations in both the cell lines; the Hx
in lagging strand is more mutagenic than in leading strand. There is also some
difference in cell types regarding the strand bias for mutation types; HEK293
cells showed largely deletion (>80%) mutations in both leading and lagging strand
and the rest were insertions and A:T->G:C transition mutations in leading and
lagging strands, respectively, whereas in HCT116 cells we observed 60% A:T->G:C
transition mutations in the leading strand and 100% deletions in the lagging
strand. Overall, Hx is a highly mutagenic lesion capable of generating A:T->G:C
transitions and large deletions with a significant variation in leading and
lagging strands in human cells. In recent meta-analysis study A->G (T->C)
mutations were found to be a prominent signature in a variety of cancers,
including a majority types that are induced by inflammation. The deletions are
known to be a major cause of copy-number variations or CNVs, which is a major
underlying cause of many human diseases including mental illness, developmental
disorders and cancer. Thus, Hx, a major DNA lesion induced by different
deamination mechanisms, has potential to initiate inflammation-driven
carcinogenesis in addition to various human pathophysiological consequences.
PMID- 28704683
TI - Visual targeting one step before force plates has no effect on gait parameters in
orthopaedic patients during level walking.
AB - In clinical gait analysis, it is challenging to acquire usable force plate data
for a patient in a limited amount of time. The aim of this study was to compare
three measurement protocols, to investigate if any one of them was more time
efficient than the others at collecting kinetic data. Three conditions were
compared for 15 orthopaedic patients: 1) approaching the force plate with four
steps, 2) approaching the force plate with six steps, and 3) approaching the
force plate with four steps while stepping on a target one step before the first
force plate. Then, the following characteristics were analysed: the rate of
usable force plate steps, the spatio-temporal parameters, the full-body gait
kinematics, and the lower body kinetics. For the condition with four steps and
targeting, the rate of usable force plate steps was highest: 84% (6.8 usable
trials out of 8.1 trials on average per patient). Left hip adduction and
rotation, right shoulder flexion, and total left hip power were the gait
parameters with statistically significant differences between the four and six
step approach. Left cadence, right step time, left thorax lateroflexion, left
shoulder abduction, total right knee power, hip rotation, thorax tilt, and head
tilt on both sides were statistically different between the four step approach
with targeting and without targeting. None of the differences in gait parameters
(except for head tilt) were of clinical relevance. Therefore, approaching the
force plate with four steps and stepping on a foot-sized target one step prior to
stepping on the force plate increases the rate of usable kinetic data.
PMID- 28704684
TI - Root mean square of lower trunk acceleration during walking in patients with
unilateral total hip replacement.
AB - Although several studies have described abnormal trunk motion before and after
total hip arthroplasty (THA) surgery, few studies have examined trunk motion
using accelerometry. The aim of this study was to determine whether abnormal
trunk motion persisted after THA using accelerometry. A total of 24 female
patients (61.0+/-6.9years) and 20 healthy female subjects (59.9+/-6.8years)
participated in this study. Patients were assessed at 1 month prior to surgery
and 12 months after surgery. Trunk acceleration during gait was measured using a
triaxial accelerometer attached to the L3 spinous process. We calculated the root
mean square (RMS) and RMS ratio (RMSR) in the vertical (VT), medio-lateral (ML),
and anterior-posterior (AP) directions. Results revealed that the RMS in the VT
and AP directions postoperatively was greater than that preoperatively, whereas
there was no difference in the RMS in the ML direction. In addition, the
preoperative RMSR in the ML direction was significantly greater compared with
that of healthy individuals and the postoperative RMSR. There was no difference
in the RMSR in the ML direction between healthy individuals and postoperatively.
These findings suggested that the trunk motion in the frontal plane prior to
surgery had improved and was comparable to that of healthy individuals following
THA.
PMID- 28704685
TI - Dynamic balance changes within three weeks of fitting a new prosthetic foot
component.
AB - Balance during walking is of high importance to prosthesis users and may affect
walking during baseline observation and evaluation. The aim of this study was to
determine whether changes in walking balance occurred during an adaptation period
following the fitting of a new prosthetic component. Margin of stability in the
medial-lateral direction (MOSML) and an anterior instability margin (AIM) were
used to quantify the dynamic balance of 21 unilateral transtibial amputees during
overground walking. Participants trialled two prosthetic feet presenting
contrasting movement/balance constraints; a Higher Activity foot similar to that
of their own prosthesis, and a Lower Activity foot. Participants were assessed
before (Visit 1) and after (Visit 2) a 3-week adaptation period on each foot.
With the Higher Activity component, MOSML decreased on the prosthetic side, and
increased on the sound side from Visit 1 to Visit 2, eliminating a significant
inter-limb difference apparent at Visit 1 (Visit 1-sound=0.062m,
prosthetic=0.075m, p=0.018; Visit 2-sound=0.066m, prosthetic=0.074m, p=0.084). No
such change was seen with the Lower Activity foot (Visit 1-sound=0.064m,
prosthetic=0.077m, p=0.007; Visit 2-sound=0.063m, prosthetic=0.080m, p<0.001).
Significant changes in AIM were observed at Visit 2 (Visit 1: -0.16 (0.08) m,
Visit 2: -0.17 (0.08) m; F=23.396, p<0.01). These findings suggest that changes
in balance during walking can occur following the initial receipt of a device
regardless of whether the component is of the same functional category as the one
an individual is accustomed to using.
PMID- 28704686
TI - A three-act play: pentachlorophenol threats to the cork oak forest soils
mycobiome.
AB - Atmospheric release of persistent organic pollutants (POPs) constitutes a silent
threat through chronic contamination of soils at global scale; yet fundamental
understanding of their occurrence, sources and fate is still largely lacking.
Similar to a three act play, this review comprises Setup, Confrontation and
Resolution. The first emphasises the eighty years of the history of
pentachlorophenol (PCP) usage, only recently classified as POP. The second focus
on active sources of PCP pollution, including inside cork oak forests in N.W.
Tunisia; a threat partially neutralised by the soil microbial diversity,
especially fungi. As Resolution, the need for improved knowledge on the global
distribution and impacts of PCP in soil microbial diversity as means to preserve
the multi-functionality of terrestrial ecosystem is emphasised.
PMID- 28704687
TI - Antimicrobial polyketide furanoterpenoids from seaweed-associated heterotrophic
bacterium Bacillus subtilis MTCC 10403.
AB - Brown seaweed Anthophycus longifolius (Turner) Kutzing (family Sargassaceae)
associated heterotrophic bacterium Bacillus subtilis MTCC 10403 was found to be a
potent isolate with broad range of antibacterial activity against important
perceptive food pathogens Vibrio parahaemolyticus, V. vulnificus, and Aeromonas
hydrophila. This bacterium was positive for polyketide synthetase gene
(KC589397), and therefore, was selected to bioprospect specialized metabolites
bearing polyketide backbone. Bioactivity-guided chromatographic fractionation of
the ethyl acetate extract of the seaweed-associated bacterium segregated four
homologous polyketide furanoterpenoids with potential antibacterial activities
against clinically important pathogens. The minimum inhibitory concentration
(MIC) assay showed that the referral antibiotics tetracycline and ampicillin were
active at 25 MUg/mL against the test pathogens, whereas the previously
undescribed (4E)-methyl 13-((16-(furan-2-yl) ethyl)-octahydro-7-hydroxy-4-((E)-23
methylbut-21-enyl)-2H-chromen-6-yl)-4-methylpent-4-enoate (compound 1) and methyl
3-(hexahydro-9-((E)-3-methylpent-1-enyl)-4H-furo[3,2-g]isochromen-6-yl)
propanoate (compound 3) displayed antibacterial activities against the test
pathogens at a lesser concentration (MIC < 7 MUg/mL). The title compounds were
characterized by comprehensive nuclear magnetic resonance and mass spectroscopic
experiments. Polyketide synthase catalyzed putative biosynthetic mechanism
additionally corroborated the structural ascriptions of the hitherto undescribed
furanoterpenoids from seaweed-associated bacterial symbiont. The electronic and
hydrophobic parameters appeared to hold a conspicuous part in directing the
antibacterial properties of the compounds. Seaweed-associated B. subtilis MTCC
10403 demonstrated to represent a potential source of antimicrobial polyketides
for pharmaceutical applications.
PMID- 28704688
TI - Occurrences, biosynthesis and properties of aurones as high-end evolutionary
products.
AB - Recent years have witnessed a considerable renewed interest for the uncommon
flavonoid class of aurones. The characterization of two major biosynthetic
machineries involved in their biosynthesis in flowers has encouraged the revival
of phytochemical studies and identification of original structures, a process
started almost seventy-five years ago. This review draws up an exhaustive map of
natural occurrences of aurones their biosynthetic pathways and roles, with the
aim to link their original structural properties among flavonoids to their place
in evolution and the selective advantages they bring to some of the most advanced
taxa in the plant kingdom.
PMID- 28704689
TI - Comprehension of synthetic speech and digitized natural speech by adults with
aphasia.
AB - Using text-to-speech technology to provide simultaneous written and auditory
content presentation may help compensate for chronic reading challenges if people
with aphasia can understand synthetic speech output; however, inherent auditory
comprehension challenges experienced by people with aphasia may make
understanding synthetic speech difficult. This study's purpose was to compare the
preferences and auditory comprehension accuracy of people with aphasia when
listening to sentences generated with digitized natural speech, Alex synthetic
speech (i.e., Macintosh platform), or David synthetic speech (i.e., Windows
platform). The methodology required each of 20 participants with aphasia to
select one of four images corresponding in meaning to each of 60 sentences
comprising three stimulus sets. Results revealed significantly better accuracy
given digitized natural speech than either synthetic speech option; however,
individual participant performance analyses revealed three patterns: (a)
comparable accuracy regardless of speech condition for 30% of participants, (b)
comparable accuracy between digitized natural speech and one, but not both,
synthetic speech option for 45% of participants, and (c) greater accuracy with
digitized natural speech than with either synthetic speech option for remaining
participants. Ranking and Likert-scale rating data revealed a preference for
digitized natural speech and David synthetic speech over Alex synthetic speech.
Results suggest many individuals with aphasia can comprehend synthetic speech
options available on popular operating systems. Further examination of synthetic
speech use to support reading comprehension through text-to-speech technology is
thus warranted.
PMID- 28704690
TI - Joint attention and oromotor abilities in young children with and without autism
spectrum disorder.
AB - PURPOSE: This study examined the relationship between joint attention ability and
oromotor imitation skill in three groups of young children with and without
Autism Spectrum Disorder using both nonverbal oral and verbal motor imitation
tasks. Research questions addressed a) differences among joint attention and
oromotor imitation abilities; b) the relationship between independently measured
joint attention and oromotor imitation, both nonverbal oral and verbal motor; c)
the relationships between joint attention and verbal motor imitation during
interpersonal interaction; and d) the relationship between the sensory input
demands (auditory, visual, and tactile) and oromotor imitation, both nonverbal
oral and verbal motor. METHOD: A descriptive, nonexperimental design was used to
compare joint attention and oromotor skills of 10 preschool-aged children with
ASD, with those of two control groups: 6 typically developing children (TD), and
6 children with suspected Childhood Apraxia of Speech (sCAS) or apraxic-like
symptoms. All children had at least a 3.0 mean length utterance. RESULTS:
Children with ASD had poorer joint attention skills overall than children with
sCAS or typically developing children. Typically developing children demonstrated
higher verbal motor imitation skills overall compared to children with sCAS.
Correlational analyses revealed that nonverbal oral imitation and verbal motor
imitation were positively related to joint attention abilities only in the
children with ASD. Strong positive relationships between joint attention in a
naturalistic context (e.g., shared story experience) and oromotor imitation
skills, both nonverbal oral and verbal motor, were found only for children with
ASD. These data suggest there is a strong positive relationship between joint
attention skills and the ability to sequence nonverbal oral and verbal motor
movements in children with ASD. The combined sensory input approach involving
auditory, visual, and tactile modalities contributed to significantly higher
nonverbal oral and verbal motor imitation performance for all groups of children.
CONCLUSIONS: Verbal children with ASD in this study had difficulties with both
the social and cognitive demands of oromotor imitation within a natural
environment that demanded cross-modal processing of incoming stimuli within an
interpersonal interaction. Further, joint attention and oral praxis may serve as
components of an important coupling mechanism in the development of spoken
communication and later developing socialcognitive skills.
PMID- 28704691
TI - Inhibition in fertilisation of coral gametes following exposure to nickel and
copper.
AB - The mining and production of nickel in tropical regions have the potential to
impact on ecologically valuable tropical marine ecosystems. Currently, few data
exist to assess the risks of nickel exposure to tropical ecosystems and to derive
ecologically relevant water quality guidelines. In particular, data are lacking
for keystone species such as scleractinian corals, which create the complex
structural reef habitats that support many other marine species. As part of a
larger study developing risk assessment tools for nickel in the tropical Asia
Pacific region, we investigated the toxicity of nickel on fertilisation success
in three species of scleractinian corals: Acropora aspera, Acropora digitifera
and Platygyra daedalea. In the literature, more data are available on the effects
of copper on coral fertilisation, so to allow for comparisons with past studies,
the toxicity of copper to A. aspera and P. daedalea was also determined. Overall,
copper was more toxic than nickel to the fertilisation success of the species
tested. Acropora aspera was the most sensitive species to nickel (NOEC < 280ug
Ni/L), followed by A. digitifera with an EC10 of 2000ug Ni/L and P. daedalea
(EC10 > 4610ug Ni/L). Acropora aspera was also the more sensitive species to
copper with an EC10 of 5.8ug Cu/L. The EC10 for P. daedalea was 16ug Cu/L,
similar to previous studies. This is the first time that the toxicity of nickel
on fertilisation success in Acropora species has been reported, and thus provides
valuable data that can contribute to the development of reliable water quality
guidelines for nickel in tropical marine waters.
PMID- 28704692
TI - Heavy metal pollution due to coal washery effluent and its decontamination using
a macrofungus, Pleurotus ostreatus.
AB - Release of the effluent generated during washing of coal became a major problem
for coal industries due to presence of many toxic metals and other pollutants.
These effluents are the main source of pollution in rivers and other water
bodies. Therefore in this study, we tried to analyse the toxicity of coal washery
effluent (CWE) collected from one of the washery plant situated in Dhanbad,
India. CWE was found to be very toxic containing large amount of suspended
particles and many heavy metals above than their permissible limits.
Mycoremediation of CWE was also performed to decontaminate heavy metals from the
CWE using a macrofungi Pleurotus ostreatus. Efficiency of Pleurotus for
remediation of heavy metals was found to be highest in the 50% diluted effluent
(57.2% Mn, 82.6% Zn, 98.0% Ni, 99.9% Cu, 99.3% Co, 99.1% Cr, 89.2% Fe and 35.6%
Pb) followed by 25% diluted effluent (33.0% Mn, 55.1% Zn, 97.8% Ni, 99.7% Cu, 97%
Co, 84.4% Cr, 87.1% Fe and 73.4% Pb) and raw effluent (23.3% Mn, 73.1% Zn, 78.7%
Ni, 87.5% Cu, 59.3% Co, 64.6% Cr, 34.6% Fe and 11.3% Pb) respectively. Increased
activity of antioxidant enzymes, lipid peroxidation, concentration of
metallothionein proteins and changes in peaks of FTIR spectra were also observed
in fungal mycelia grown on the CWE containing media due to accumulation of
different metals. Overall this study suggests that Pleurotus can be used as
promising option for removal of heavy metals from the effluent released from
washery plants and dilution of effluent could increase the efficiency of
remediation.
PMID- 28704693
TI - Investigation of arsenic accumulation and biochemical response of in vitro
developed Vetiveria zizanoides plants.
AB - Vetiver grass (Vetiveria zizanoides L. Nash) is found to be a suitable candidate
for the phytoremediation of heavy metals. An investigation of arsenic (As)
accumulation, translocation and tolerance was conducted in V. zizanoides
plantlets upon exposure to different concentrations of arsenic (10, 50, 100 and
200uM) for 7 and 14 d. V. zizanoides plants were found effective in remediation
of As, maximum being at 200uM after 14 d of exposure. The results of TBARS and
photosynthetic pigments demonstrated that plants did not experience significant
toxicity at all the concentrations of As after 7 days, however an increase in
their level was found after 14 d. The up-regulation of antioxidant enzyme
activities of superoxide dismutase (SOD), ascorbate peroxidase (APX), guaiacol
peroxidase (GPX), catalase (CAT) and glutathione s-transferase (GST) in a
coordinated and complementary manner enhanced tolerance to plants against arsenic
induced oxidative stress. Taken together, the results indicated that in vitro
developed plants of V. zizanoides have the potential to remediate and tolerate
varying levels of As.
PMID- 28704694
TI - Harmony as a convergence attractor that minimizes the energy expenditure and
variability in physiological gait and the loss of harmony in cerebellar ataxia.
AB - BACKGROUND: The harmony of the human gait was recently found to be related to the
golden ratio value (phi). The ratio between the duration of the stance and that
of the swing phases of a gait cycle was in fact found to be close to phi, which
implies that, because of the fractal property of autosimilarity of that number,
the gait ratios stride/stance, stance/swing, swing/double support, were not
significantly different from one another. We studied a group of patients with
cerebellar ataxia to investigate how the differences between their gait ratios
and the golden ratio are related to efficiency and stability of their gait,
assessed by energy expenditure and stride-to-stride variability, respectively.
METHODS: The gait of 28 patients who were affected by degenerative cerebellar
ataxia and of 28 healthy controls was studied using a stereophotogrammetric
system. The above mentioned gait ratios, the energy expenditure estimated using
the pelvis reconstructed method and the gait variability in terms of the stride
length were computed, and their relationships were analyzed. Matching procedures
have also been used to avoid multicollinearity biases. FINDINGS: The gait ratio
values of the patients were farther from the controls (and hence from phi), even
in speed matched conditions (P=0.011, Cohen's D=0.76), but not when the
variability and energy expenditure were matched between the two groups (Cohen's
D=0.49). In patients with cerebellar ataxia, the farther the stance-swing ratio
was from phi, the larger the total mechanical work (R2adj=0.64). Further, a
significant positive correlation was observed between the difference of the gait
ratio from the golden ratio and the severity of the disease (R=0.421, P=0.026).
INTERPRETATION: Harmony of gait appears to be a benchmark of physiological gait
leading to physiological energy recovery and gait reliability.
Neurorehabilitation of patients with ataxia might benefit from the restoration of
harmony of their locomotor patterns.
PMID- 28704695
TI - Emergence of the Asian genotype of DENV-1 in South India.
AB - A large outbreak of dengue occurred in Tamil Nadu, South India in 2012 with
12,000 cases and CFR of 0.5%. Molecular characterization of virus present in the
sera of dengue patients was undertaken to determine if there were changes in the
virus population. All four serotypes were circulating but DENV-1 was dominant,
present in 52% of the serotyped samples. Furthermore, the genotype of only DENV-1
had changed; the Asian genotype had displaced the American/African. Phylogenetic
analysis revealed that the Asian genotype was introduced from Singapore and
shared 99% similarity with viruses, associated with large outbreaks in Singapore
and Sri Lanka. We report for the first time the emergence of the Asian genotype
of DENV-1 in southern India causing an extensive and severe outbreak. The study
proves how movement of DENV can affect dengue outbreaks and underscores the need
for close molecular monitoring of DENV.
PMID- 28704697
TI - The use of ultrasound in the clinical re-staging of the axilla after neoadjuvant
chemotherapy (NACT).
AB - INTRODUCTION: Ultrasound (US) is the imaging modality of choice for staging the
axilla prior to surgery in patients with breast cancer (BC). High pathological
complete response rates in the axilla after NACT mean a more conservative
approach to surgery can be considered. Radiological re-staging is important in
this decision making. After the presentation of results from ACOSOG Z1071 in
December 2012, formal ultrasound re-assessment of the axilla after primary
therapy was specifically requested in our institution. We report on the accuracy
of axillary US (aUS) for identifying residual axillary disease post-NACT.
METHODS: Data were collected on patients who had proven axillary disease prior to
NACT and underwent axillary lymph node dissection after NACT between January 2013
and December 2015. Post-chemotherapy aUS reports and axillary pathology reports
were classified as positive or negative for abnormal lymph nodes and for residual
disease (cCR and pCR respectively). RESULTS: The sensitivity and specificity of
aUS was 71% and 88% respectively. The negative predictive value (NPV) was 83%.
The false negative rate was 29%. CONCLUSIONS: Axillary ultrasound provides
clinically useful information post-NACT, which will guide surgical decision
making. Patients with aUS-negative axillae are likely to have a lower false
negative rate of SLNB after NACT (Boughey et al.). However, aUS does not replace
the need to identify and biopsy the nodes which were proven to be positive prior
to NACT.
PMID- 28704696
TI - The function of DNA binding protein nucleophosmin in AAV replication.
AB - Adeno-associated viruses (AAV) contain minimal viral proteins necessary for their
replication. During virus assembly, AAV acquire, inherently and submissively,
various cellular proteins. Our previous studies identified the association of AAV
vectors with the DNA binding protein nucleophosmin (NPM1). Nucleophosmin has been
reported to enhance AAV infection by mobilizing AAV capsids into and out of the
nucleolus, indicating the importance of NPM1 in the AAV life cycle; however the
role of NPM1 in AAV production remains unknown. In this study, we systematically
investigated NPM1 function on AAV production using NPM1 knockdown cells and
revealing for the first time the presence of G-quadruplex DNA sequences (GQRS) in
the AAV genome, the synergistic NPM1-GQRS function in AAV production and the
significant enhancement of NPM1 gene knockdown on AAV vector production.
Understanding the role of cellular proteins in the AAV life cycle will greatly
facilitate high titre production of AAV vectors for clinical use.
PMID- 28704698
TI - Interventional radiology in breast cancer.
AB - Molecular profiling of metastatic disease may greatly influence the systemic
therapy recommended by oncologists and chosen by patients, allowing treatment to
be more targeted. Comprehensive care of patients with advanced breast cancer now
includes percutaneous image-guided biopsy if this has the potential to influence
systemic treatment [1]. Interventional radiologists can contribute significantly
to the care of patients affected by breast cancer, in diagnostic and supportive
procedures and importantly also in treatment. Interventional radiologists carry
out image guided percutaneous biopsies not only of the primary tumour but also of
metastases. They insert percutaneous ports and tunnelled central venous
catheters. They ablate painful bone metastases, and can treat or prevent
pathological fractures. Most importantly they can ablate liver metastases in
patients with limited or oligometastatic disease. The inhomogeneity and variety
of cell populations in metastatic tumours from breast cancer, which is an
important consideration in systemic therapy, is not an important consideration in
the treatment of metastatic tumours using percutaneous ablative techniques, which
are the major focus of this article. The treatment of primary tumours in the
breast is also being explored, but is considered in its infancy at this stage.
PMID- 28704699
TI - Comparison of the ability to identify arterial stiffness between two new
anthropometric indices and classical obesity indices in Chinese adults.
AB - BACKGROUND AND AIMS: The association between anthropometric indices of body
composition and arterial stiffness is inconclusive. The objective of this study
was to examine the predictive ability of two new obesity indices: a body shape
index (ABSI), and a body roundness index (BRI), for the identification of
arterial stiffness among Chinese adults, as well as to compare the relative
strength of association between the anthropometric indices and arterial
stiffness. METHODS: A total of 10,197 subjects were recruited in this cross
sectional study. We tested the association between anthropometric indices (body
mass index [BMI], waist circumference [WC], waist-height-ratio [WHtR], ABSI and
BRI) and brachial-ankle pulse wave velocity (PWV). Receiver operating
characteristic curve and area under curve (AUC) were employed to evaluate the
predictive value of the anthropometric indices for identification of arterial
stiffness. RESULTS: After adjusting for confounding variables, BRI (linear
regression: 0.112; AUC: 0.726; OR: 1.228 for female and linear regression: 0.047;
AUC: 0.631; OR: 1.173 for male) exhibited a more powerful predictive ability of
arterial stiffness than ABSI (linear regression: 0.110; AUC: 0.674; OR: 1.315 for
female and linear regression: 0.058; AUC: 0.610; OR: 1.150 for male) and WC
(linear regression: 0.078; AUC: 0.699; logistic regression: negative for female
and linear regression: negative; AUC: 0.593; logistic regression: negative for
male) while having a similar predictive value to that of WHtR (linear regression:
0.113; AUC: 0.726; OR: 1.228 for female and linear regression: 0.047; AUC: 0.631;
OR: 1.185 for male) among both sexes. BMI (linear and logistic regression:
negative; AUC: 0.660 for female and 0.568 for male) had the lowest predictive
power in both sex categories. The optimal cut-off of WHtR for detecting arterial
stiffness was 0.49 in females and 0.53 in males, that of BRI was 3.19 in females
and 3.89 in males. CONCLUSIONS: WHtR, ABSI and BRI were significantly associated
with arterial stiffness. BRI and WHtR, rather than ABSI, showed superior
predictive abilities for arterial stiffness in both sexes.
PMID- 28704700
TI - Environmental exposure to pesticides and the risk of Parkinson's disease in the
Netherlands.
AB - BACKGROUND: Exposure to pesticides has been linked to Parkinson's disease (PD),
although associations between specific pesticides and PD have not been well
studied. Residents of rural areas can be exposed through environmental drift and
volatilization of agricultural pesticides. OBJECTIVES: Our aim was to investigate
the association between lifetime environmental exposure to individual pesticides
and the risk of PD, in a national case-control study. METHODS: Environmental
exposure to pesticides was estimated using a spatio-temporal model, based on
agricultural crops around the residential address. Distance up to 100m from the
residence was considered most relevant, considering pesticide drift potential of
application methods used in the Netherlands. Exposure estimates were generated
for 157 pesticides, used during the study period, of which four (i.e. paraquat,
maneb, lindane, benomyl) were considered a priori relevant for PD. RESULTS: A
total of 352 PD cases and 607 hospital-based controls were included. No
significant associations with PD were found for the a priori pesticides. In a
hypothesis generating analysis, including 153 pesticides, increased risk of PD
was found for 21 pesticides, mainly used on cereals and potatoes. Results were
suggestive for an association between bulb cultivation and PD. CONCLUSIONS: For
paraquat, risk estimates for the highest cumulative exposure tertile were in line
with previously reported elevated risks. Increased risk of PD was observed for
exposure to (a cluster of) pesticides used on rotating crops. High correlations
limited our ability to identify individual pesticides responsible for this
association. This study provides some evidence for an association between
environmental exposure to specific pesticides and the risk of PD, and generates
new leads for further epidemiological and mechanistic research.
PMID- 28704701
TI - "Developing culturally sensitive affect scales for global mental health research
and practice: Emotional balance, not named syndromes, in Indian Adivasi
subjective well-being".
AB - We present a perspective to analyze mental health without either a) imposing
Western illness categories or b) adopting local or "native" categories of mental
distress. Our approach takes as axiomatic only that locals within any culture
share a cognitive and verbal lexicon of salient positive and negative emotional
experiences, which an appropriate and repeatable set of ethnographic procedures
can elicit. Our approach is provisionally agnostic with respect to either Western
or native nosological categories, and instead focuses on persons' relative
frequency of experiencing emotions. Putting this perspective into practice in
India, our ethnographic fieldwork (2006-2014) and survey analysis (N = 219)
resulted in a 40-item Positive and Negative Affect Scale (PANAS), which we used
to assess the mental well-being of Indigenous persons (the tribal Sahariya) in
the Indian states of Rajasthan and Madhya Pradesh. Generated via standard
cognitive anthropological procedures that can be replicated elsewhere, measures
such as this possess features of psychiatric scales favored by leaders in global
mental health initiatives. Though not capturing locally named distress syndromes,
our scale is nonetheless sensitive to local emotional experiences, frames of
meaning, and "idioms of distress." By sharing traits of both global and also
locally-derived diagnoses, approaches like ours can help identify synergies
between them. For example, employing data reduction techniques such as factor
analysis-where diagnostic and screening categories emerge inductively ex post
facto from emotional symptom clusters, rather than being deduced or assigned a
priori by either global mental health experts or locals themselves-reveals hidden
overlaps between local wellness idioms and global ones. Practically speaking, our
perspective, which assesses both emotional frailty and also potential sources of
emotional resilience and balance, while eschewing all named illness categories,
can be deployed in mental health initiatives in ways that minimize stigma and
increase both the acceptability and validity of assessment instruments.
PMID- 28704702
TI - Plant architecture, auxin homeostasis and phenol content in Arabidopsis thaliana
grown in cadmium- and zinc-enriched media.
AB - A screening strategy using micropropagation glass tubes with a gradient of
distances between germinating seeds and a metal-contaminated medium was used for
studying alterations in root architecture and morphology of Arabidopsis thaliana
treated with cadmium (Cd) and zinc (Zn) at the concentration of 10-20MUM and 100
200MUM, respectively. Metal concentrations in plant shoots and roots were
measured by quadrupole inductively coupled plasma mass spectrometry. After 21days
from germination, all plants in the tubes were scanned at high resolution and the
root systems analyzed. The localization of indole-3-acetic acid (IAA) in the
primary root and lateral root apices was monitored using DR5:GUS, LAX3:GUS and
AUX1:GUS Arabidopsis transgenic lines. Total phenol content in leaves was
measured spectrophotometrically. Shoot and root dry weight and leaf area did not
change in Zn-exposed plants and significantly decreased in Cd-exposed plants,
compared to control plants. Cadmium induced a reduction of root length, of mean
number of roots and of total root surface. Both Cd- and Zn-exposed plants showed
a reduced specific root length. This morphological behavior, together with an
observed increase in root diameter in metal-exposed plants could be interpreted
as compensatory growth, and the observed thicker roots could act as a barrier to
protect root from the metals. In comparison with the apical localization of the
IAA signal in the control plants, Zn generally reinforced the intensity of IAA
signal, without affecting its localization. In Cd-exposed plants, IAA
localization remained apical but weaker compared to control plants. Total phenols
decreased in plants exposed to Zn and Cd. Therefore, we propose that the
remodelling of the root architecture and the production of some secondary
metabolites, such as IAA and phenols could be two responses of plants subjected
to metal stress. This knowledge can open the way to future phytoremediation
strategies of contaminated sites.
PMID- 28704703
TI - Early axis growth during seed germination is gravitropic and mediated by ROS and
calcium.
AB - In plant establishment, seed germination is characterized by the emergence of a
radicle for secured anchorage to the soil and nutrient and water uptake. Early
growth of germinating axes appears to be gravisensitive, and the regulation of
this process is largely uncharacterized, particularly in case of epigeally
germinating species. Our previous work on the germination of Vigna radiata seeds
demonstrated the role of apoplastic reactive oxygen species (ROS) in germination
associated axis growth. This study attempts to explore a possibly similar role of
ROS in the gravitropic bending of germinating axes. Pharmacological and
histological studies correlated the curvature growth of the axis (due to cell
elongation in the cortical region of the upper side) with apoplastic superoxide
accumulation. The superoxide was produced by diphenylene iodonium chloride (DPI)
insensitive NADH oxidase, which was different from the DPI-sensitive NADPH
oxidase active in the apical elongation zone of the radicle. This NADH oxidase
was differentially controlled by IAA, and its activation required influx of
apoplastic Ca2+. This study shows that the early axis growth in germinating seeds
is gravisensitive, which is distinct spatially as well as temporally from the
elongation growth of the axis (radicle) and controlled by auxin and cytosolic
Ca2+ through NADH oxidase-dependent ROS production.
PMID- 28704704
TI - The role of monocytes in models of infection by protozoan parasites.
AB - The confirmation of developmental differences between tissue macrophages and
peripheral monocytes has changed our view of the functions and dynamics of these
two important components of the innate immune system. It has been demonstrated
conclusively that homeostasis of tissue resident macrophages is maintained by a
low proliferative turn over. During an inflammatory response, bone marrow derived
monocytes enter the tissue in large numbers and take part in the defense against
the pathogens. After the destruction of invading pathogens, these cells disappear
and tissue resident macrophages can be detected again. This new appreciation of
the innate immune response has not only answered many outstanding questions
regarding the role of the different myeloid cell types in inflammation, but also
opened up new areas of research relating to the tissue- and pathogen-specific
fate of the inflammatory macrophages or dendritic cells (DCs), and the transfer
of this knowledge from mouse models to the human immune system. Nevertheless,
there is still confusion in infection models, and especially in studies of human
infections, as to what extent these recent observations and findings influence
previous interpretations of data. This review will focus on insights from mouse
models, summarize the literature on the ontogeny of macrophages and monocytes,
explain the role of frequently used monocyte markers and effector molecules, and
finally, discuss the role of inflammatory monocytes/macrophages/DCs in two
experimental parasitic diseases.
PMID- 28704705
TI - A New Parasitic Chytrid, Staurastromyces oculus (Rhizophydiales,
Staurastromycetaceae fam. nov.), Infecting the Freshwater Desmid Staurastrum sp.
AB - Chytrids are a diverse group of ubiquitous true zoosporic fungi. The recent
molecular discovery of a large diversity of undescribed chytrids has raised
awareness on their important, but so far understudied ecological role in aquatic
ecosystems. In the pelagic zone, of both freshwater and marine ecosystems, many
chytrid species have been morphologically described as parasites on almost all
major groups of phytoplankton. However, the majority of these parasitic chytrids
has rarely been isolated and lack DNA sequence data, resulting in a large
proportion of "dark taxa" in databases. Here, we report on the isolation and in
depth morphological, molecular and host range characterization of a chytrid
infecting the common freshwater desmid Staurastrum sp. We provide first insights
on the metabolic activity of the different chytrid development stages by using
the vital dye FUN(r)-1 (2-chloro-4-[2,3-dihydro-3-methyl-[benzo-1,3-thiazol-2-yl]
methylidene]-1-phenylquinolinium iodide). Cross infection experiments suggest
that this chytrid is an obligate parasite and specific for the genus Staurastrum
sp. Phylogenetic analysis, based on ITS1-5.8S-ITS2 and 28S rDNA sequences, placed
it in the order Rhizophydiales. Based on the unique zoospore ultrastructure,
combined with thallus morphology, and molecular phylogenetic placement, we
describe this parasitic chytrid as a new genus and species Staurastromyces
oculus, within a new family Staurastromycetaceae.
PMID- 28704706
TI - IL-17B: A new area of study in the IL-17 family.
AB - The interleukin (IL)-17 superfamily, a relatively new family of cytokines,
consists of six ligands (from IL-17A to IL-17F), which bind to five receptor
subtypes (from IL-17RA to IL-17RE) and induce downstream signaling. IL-17A, a
prototype member of this family, has been reported to be involved in the
pathogenesis of allergies, autoimmune diseases, allograft transplantations, and
malignancies. Unlike IL-17A, which is mainly produced by T helper 17 cells, IL
17B is widely expressed in various tissues. Recently, the biological function of
IL-17B in diseases, particularly tumors, has attracted the attention of
researchers. We previously reported that the expression of IL-17RB increased in
gastric cancer tissues and demonstrated that IL-17B/IL-17RB signaling plays a
critical role in gastric tumor progression. However, studies on IL-17B are scant.
In this review, we detail the structural characteristics, expression patterns,
and biological activities of IL-17B and its potential role in the pathogenesis of
diseases.
PMID- 28704707
TI - A founder mutation underlies a severe form of phosphoglutamase 3 (PGM3)
deficiency in Tunisian patients.
AB - Phosphoglucomutase 3 (PGM3) protein catalyzes the conversion of N-acetyl-d
glucosamine-6-phosphate (GlcNAc-6-P) to N-acetyl-d-glucosamine-1-phosphate
(GlcNAc-1-P), which is required for the synthesis of uridine diphosphate N
acetylglucosamine (UDP-GlcNAc) an important precursor for protein glycosylation.
Mutations in PGM3 gene have been recently shown to underlie a new congenital
disorder of glycosylation often associated to elevated IgE. Herein, we report
twelve PGM3 deficient patients. They belong to three highly consanguineous
families, originating from a rural district in the west central Tunisia. The
patient's clinical phenotype is characterized by severe respiratory and cutaneous
infections as well as developmental delay and severe mental retardation. Fourteen
patients died in early infancy before diagnosis supporting the severity of the
clinical phenotype. Laboratory findings revealed elevated IgE, CD4 lymphopenia
and impaired T cell proliferation in most patients. Genetic analysis showed the
presence, of a unique homozygous mutation (p.Glu340del) in PGM3 gene leading to
reduced PGM3 abundance. Segregating analysis using fifteen polymorphic markers
overlapping PGM3 gene showed that all patients inherited a common homozygous
haplotype encompassing 10-Mb on chromosome 6. The founder mutational event was
estimated to have occurred approximately 100 years ago. To date, (p.Glu340del)
mutation represents the first founder mutation identified in PGM3 gene. These
findings will facilitate the development of preventive approaches through genetic
counselling and prenatal diagnosis in the affected families.
PMID- 28704708
TI - Innate immunity related pathogen recognition receptors and chronic hepatitis B
infection.
AB - Innate immunity consists of several kinds of pathogen recognition receptors
(PRRs), which participate in the recognition of pathogens and consequently
activation of innate immune system against pathogens. Recently, several
investigations reported that PRRs may also play key roles in the
induction/stimulation of immune system related complications in microbial
infections. Hepatitis B virus (HBV), as the main cause of viral hepatitis in
human, can induce several clinical forms of hepatitis B and also might be
associated with hepatic complications such as cirrhosis and hepatocellular
carcinoma (HCC). Based on the important roles of PRRs in the eradication of
microbial infections including viral infections and their related complications,
it appears that the molecules may be a main part of immune responses against
viral infections including HBV and participate in the HBV related complications.
Thus, this review article has brought together information regarding the roles of
PRRs in immunity against HBV and its complications.
PMID- 28704709
TI - Protective role of surface Toll-like receptor 9 expressing neutrophils in local
inflammation during systemic inflammatory response syndrome in mice.
AB - Clinically, systemic inflammatory response syndrome (SIRS) occurs after serious
trauma or sepsis. In sepsis, neutrophils are the major effector cells responsible
for eliminating pathogens. However, the role of neutrophils in development of
SIRS, especially in local inflammatory area, is controversial. In this study, we
established a SIRS mouse model characterized with cytokine-mediated lethal shock
by intraperitoneal injection of oligodexynucleotides containing CpG motifs (CpG
ODN) in D-galactosamine (D-GalN) sensitized mice based on our previous work and
found that abundant neutrophils were rapidly recruited into the peritoneal
cavity, where some neutrophils expressed surface TLR9 (sTLR9), defined as sTLR9+
neutrophils. Along with the progression of SIRS, the expression of sTLR9 in
sTLR9+ neutrophils isolated from peritoneal lavage cells (PLCs) was declined in
accompany with an increase in the level of the inflammatory cytokine TNFalpha and
a decrease in the level of the anti-inflammatory cytokine IL-10 in Ly6G+ PLCs.
When using CCT ODN, an oligodeoxynucleotide with CCT repeats, which we have
previously shown to be capable of rescuing mice from lethal shock, the expression
of sTLR9 on neutrophils was significantly elevated. Adoptive therapy using early
recruited neutrophil-rich PLCs containing sTLR9+ neutrophils that express high
levels of sTLR9, could rescue mice from SIRS. Overall, the data reveal that the
early recruited sTLR9+ neutrophils may, at least in the area of local
inflammation, play a protective role during SIRS development and provide a method
to rescue the patients with severe SIRS via the up-regulation of sTLR9 levels on
the surface of neutrophils or via adoptive therapy with protective sub
populations of neutrophils.
PMID- 28704710
TI - Dissecting the Biological Heterogeneity within Hormone Receptor Positive HER2
Negative Breast Cancer by Gene Expression Markers Identifies Indolent Tumors
within Late Stage Disease.
AB - Hormone receptor positive (HR+) breast cancers are a heterogeneous class with
differential prognosis. Although more than half of Indian women present with
advanced disease, many such patients do well. We have attempted identification of
biologically indolent tumors within HR+HER2- tumors based on gene expression
using histological grade as a guide to tumor aggression. 144 HR+HER2- tumors were
divided into subclasses based on scores derived by using transcript levels of
multiple genes representing survival, proliferation, and apoptotic pathways and
compared to classification by Ki-67 labeling index (LI). Clinical characters and
disease free survival were compared between the subclasses. The findings were
independently validated in the METABRIC data set. Using the previously
established estrogen receptor (ER) down stream activity equation, 20% of the
tumors with greater than 10% HR positivity by immunohistochemistry (IHC) were
still found to have inadequate ER function. A tumor aggression probability score
was used to segregate the remainder of tumors into indolent (22%) and aggressive
(58%) classes. Significant difference in disease specific survival was seen
between the groups (P = .02). Aggression probability based subclassification had
a higher hazard ratio and also independent prognostic value (P<.05). Independent
validation of the gene panel in the METABRIC data set showed all 3 classes;
indolent (24%), aggressive (68%), and insufficient ER signaling (7%) with
differential survival (P = .01). In agreement with other recent reports,
biologically indolent tumors can be identified with small sets of gene panels and
these tumors exist in a population with predominantly late stage disease.
PMID- 28704711
TI - Insomnia moderates the association between alcohol use and consequences among
young adult veterans.
AB - OBJECTIVE: Symptoms of insomnia and heavy alcohol use tend to co-occur among
military and veteran samples. The current study examined insomnia as a moderator
of the association between alcohol use and related consequences among young adult
veterans in an effort to extend and replicate findings observed in samples of
civilian young adults. METHOD: Young adult veterans (N=622; 83% male; age M=29.0,
SD=3.4) reporting alcohol use in the past year completed measures of insomnia
severity, alcohol use, and alcohol-related consequences as part of a larger
intervention trial. Participants were classified as screening 'positive' (n=383,
62%) or 'negative' (n=239, 38%) for insomnia using the Insomnia Severity Index.
Hierarchical regression was used to examine the interaction between drinking
quantity and insomnia on alcohol-related consequences. Predictor and outcome
variables were measured concurrently. RESULTS: Both a greater number of drinks
per week and a positive insomnia screen were associated with more alcohol-related
consequences. Drinks per week and insomnia screen interacted to predict alcohol
related consequences, such that the effect of drinking on alcohol-related
consequences was stronger in the context of a positive versus negative insomnia
screen. CONCLUSION: Drinking is associated with more alcohol-related consequences
in the presence of clinically significant insomnia symptoms. These findings
replicate those documented in civilian young adults and indicate that insomnia
may be an appropriate target for alcohol prevention and intervention efforts
among young adult veterans.
PMID- 28704712
TI - Multipurpose efficacy of ZnO nanoparticles coated by the crustacean immune
molecule beta-1, 3-glucan binding protein: Toxicity on HepG2 liver cancer cells
and bacterial pathogens.
AB - The effective treatment of cancer and bacterial pathogens are two key challenges
in modern nanomedicine. Here, zinc oxide nanoparticles (ZnO NPs) were fabricated
using the crustacean immune molecule beta-1, 3- glucan binding protein (Phbeta
GBP, 100kDa) purified from the heamolymph of Paratelphusa hydrodromus. beta-GBP
coated zinc oxide nanoparticles (Phbeta-GBP-ZnO NPs) were characterized by UV-vis
spectroscopy, X-ray diffraction (XRD), Fourier transform infrared spectroscopy
(FTIR), and high resolution-transmission electron microscopy (HR-TEM) analyses.
Phbeta-GBP-ZnO NPs inhibited the growth of Staphylococcus aureus and Proteus
vulgaris. Protein and nucleic acid leakage assays showed that Phbeta-GBP-ZnO NPs
facilitate membrane permeability leading to cell death. The antibacterial
activity of Phbeta-GBP-ZnO NPs was due to the high level of reactive oxygen
species (ROS) release from bacterial cells post-treatment with 75MUg/mL of Phbeta
GBP-ZnO NPs. Confocal laser scanning microscopy pointed out that biofilm
thickness was highly reduced post-treatment with nanoparticles. Cytotoxicity on
human liver carcinoma (HepG2) cells highlighted that 75MUg/mL of Phbeta-GBP-ZnO
NPs inhibited viability of HepG2 cells. Phase contrast microscopy showed key
morphological changes of HepG2 cells post-treatment with Phbeta-GBP-ZnO NPs.
Overall, Phbeta-GBP-ZnO NPs can be further considered for the development of
novel drugs against microbial pathogens and HepG2 cells.
PMID- 28704713
TI - Cation-chelation and pH induced controlled switching of the non-fouling
properties of bacterial crystalline films.
AB - We report the controlled loss of the anti-fouling activity of the S-layer protein
SbpA from Lysinibacillus sphaericus (CCM2177). This protein forms crystal-like
films with square lattice (p4) via self-assembly on almost any type of surfaces.
Such engineered bioinspired nanometric membranes are known by their excellent
preventive performance under biological conditions. However, their exposure to
certain treatments can lead to gradual degradation of the S-protein layer. In
this work, two distinctive approaches are studied for understanding either
specific or non-specific degradation of the film, by treatment with a chelating
agent (EDTA), which interacts with inner Ca2+ ions, or Citrate buffer (with
pH=0.99 with a linear array for the
calibration curve from 0 to 20 ppbv. The limit of quantification was 0.3 ppbv and
the limit of detection was 0.1 ppbv. The device is able to distinguish
concentration differences >0.5 ppbv for the concentration range between 2 and 4
ppbv and >0.9 ppbv for the range between 28 and 30 ppbv. The imprecision at 20
ppbv is 11.3% whereas it is 3.5% at a concentration of 40 ppbv. The carry-over
duration is 3min. The MCC/IMS we tested provided online quantification of gaseous
propofol over the clinically relevant range at measurement frequencies of one
measurement each minute.
PMID- 28704719
TI - Biochemical and functional analysis of corticotropin releasing factor purified
from an aqueous extract of human placenta used as wound healer.
AB - Human placental extract constitutes of innumerable therapeutically important
components mostly used in wound healing arising from the skin and burn injuries.
However, there is still some bioactive present in the placental extracts yet to
be characterized to better under the complex process of wound healing mediated by
the placental extract. In this study, the presence of corticotropin releasing
factor (CRF) in an aqueous extract of human placenta was detected and quantified
by dot blot and CRF-ELISA immunoassay kit respectively. Subsequently, it was
purified by immuno-affinity chromatography and quantified as 0.45+/-0.05MUg of
CRF per ml of placental extract where its molecular weight found to be 4.78kDa by
MALDI-TOF. To study functional analysis of CRF, an in vitro WI-38 lung fibroblast
cell scratch wound model was used which indicated proliferation, motility of
cells after treatment with purified CRF. Moreover, reduction in apoptosis rate of
cells during closure of wound was observed from microscopy studies and FACS
analysis. Also, Antalarmin, an antagonist of CRF type 1 receptor inhibited the
wound closure potency of the purified component. Faster healing of wound with an
elevation of IL-6 and TGF-beta during early stages of repair by placental CRF was
observed on excision rat model. The process of healing was accompanied by the
decrease in the level of TNF-alpha and IFN-gamma.
PMID- 28704720
TI - The Dana Farber consortium protocol (DFCP) vs. classic Hyper-CVAD for treatment
of acute lymphoblastic leukemia in patients <50 Y. Single institution experience.
AB - BACKGROUND: The use of intensive pediatric protocols for the treatment of ALL is
being extended to older adults. AIM OF THE STUDY: Analysis of the efficacy and
toxicity results of pediatric DFCP vs. classic Hyper-CVAD protocol for the
treatment of patients with ALL < 50 Y. PATIENTS AND METHODS: A retrospective
single center comparative analysis of DFCP & classic Hyper-CVAD for first line
treatment of patients with ALL < 50 Y. RESULTS: 73 patients were included, 43
received DFCP and 30 received Hyper-CVAD protocol. CR rate was 90.7% for DFCP vs.
83.7 for Hyper-CVAD (p 0.7). 3 Y Leukemia free survival was 57.4% (70.9% for DFCP
vs. 41.6% Hyper-CVAD P 0.1) while 3Y OS was 62.6%% for the whole group, 72.6%
DFCP vs. 48.5% Hyper-CVAD, P 0.04. Those with age <21 Y, had significantly longer
3 Y LFS and OS (P 0.04, 0.02, respectively). TOXICITY: pancreatitis occurred in 5
patients with DFCP and it was related to Asparginase and in 1 patient on Hyper
CVAD related to gall stones. Osteonecrosis affected 5 patients on DFCP. IN
CONCLUSION: pediatric protocols are feasible in patients younger than 50 Y and
they are more active than classic adult protocols. Although modifications of
adult protocols may improve their results, this had to be investigated in
randomized controlled trials.
PMID- 28704721
TI - Paid HIV rapid testing in general medicine private practice in French Guiana: a
pilot project.
PMID- 28704722
TI - Arsanilic acid modified superparamagnetic iron oxide nanoparticles for
Purification of alkaline phosphatase from hen's egg yolk.
AB - Recent studies of magnetic carrier technology have focused on its applications in
separation and purification technologies, due to easy separation of the target
from the reaction medium by applying an external magnetic field. In the present
study, Fe3O4 superparamagnetic nanoparticles were prepared to utilize a chemical
co-precipitation method, then the surfaces of the nanoparticles were modified
with arsanilic acid derivatives which were used as the specific nanocarriers for
the affinity purification of alkaline phosphatase from the hen's egg yolk. The
six different types of magnetic nanocarriers with varied lengths of the linkers
were obtained. All samples were characterized step by step and validated using
FTIR, SEM, EDX, VSM and XRD analysis methods As the results were shown, the use
of inflexible tags with long linkers on the surface of the nanocarrier could lead
to better results for separation of alkaline phosphatase from the hen's egg yolk
with 76.2% recovery and 1361.7-fold purification. The molecular weight of the
purified alkaline phosphatase was estimated to be 68kDa by SDS-PAGE. The results
of this study showed that the novel magnetic nanocarriers were capable of
purifying alkaline phosphatase in a practically time and cost effective way.
PMID- 28704723
TI - Highly sensitive determination of fatty acid esters of hydroxyl fatty acids by
liquid chromatography-mass spectrometry.
AB - Recently, a new class of endogenous lipids, branched fatty acid esters of hydroxy
fatty acids (FAHFAs), was discovered with anti-diabetic and anti-inflammatory
effects in mammals. FAHFAs attracted increasing attention because of their
critical physiological function. However, accurate quantitation of FAHFAs is
still a challenge due to their high structure similarity and low abundance in
biological samples. Herein, we developed a highly sensitive method for the
determination of 16 FAHFAs (PAHSAs, OAHSAs, SAHSAs and POHSAs) in biological
samples by coupling strong anion exchange solid phase extraction (SAX-SPE) with
chemical labeling assisted ultra-high performance liquid chromatography/mass
spectrometry (SAX-SPE-CL-UHPLC/MS). In the developed method, SAX-SPE was employed
to selectively enrich and purify FAHFAs from biological samples. And then a pair
of isotope labeling reagents, 2-dimethylaminoethylamine (DMED) and d4-DMED were
used to label the purified samples and standard FAHFAs, respectively. The labeled
samples were mixed and further subjected to UHPLC/MS analysis. Our results
demonstrated that the detection sensitivities of FAHFAs increased by 7-72 folds
upon DMED labeling and the limits of detections (LODs) of labeled FAHFAs ranged
from 0.01 to 0.14pg. Moreover, a good separation of FAHFAs isomers was achieved
on C18 column in a UHPLC system and all FAHFAs could be analyzed in 20min with
sharp peak shape. The established method provided substantial sensitivity, high
specificity, and broad linear dynamic range (3 orders of magnitude). Using this
method, we successfully measured the contents and distribution of FAHFAs in rat
white adipose, lung, kidney, thymus, liver and heart tissues. The results showed
that 7 FAHFAs (13-, 12-, 9-, 5-PAHSA, 13-, 12- and 9-SAHSA) were observed in
different tissues of rat. In addition, we successfully detected the above 7
FAHFAs in human serum samples; and among the 7 FAHFAs, 13-, 9-PAHSA, 13- and 12
SAHSA were found remarkably decreased in human breast cancer serum. The proposed
method could be successfully applied for the detection of FAHFAs in various
biological samples, which will facilitate the understanding of the physiological
functions of FAHFAs.
PMID- 28704724
TI - Development of immunoaffinity solid phase microextraction rods for analysis of
three estrogens in environmental water samples.
AB - In this study, immunoaffinity solid phase microextraction (SPME) rods were
developed for the analysis of diethylstilbestrol (DES), hexestrol (HES) and
dienestrol (DIS) followed by ultra high-performance liquid chromatography-tandem
mass spectrometry (UPLC-MS/MS). This immunoaffinity SPME device was built with
three stainless steel rods bundled together as one and modified with porous
silicate particles. As an extraction sorbent, antibody immobilization approach
was employed based on the covalent attachment of the anti-diethylstilbestrol
monoclonal antibody (mAb) onto the rods. The immunoaffinity SPME rod was
characterized and confirmed by scanning electron microscopy and X-ray
photoelectron spectroscopy analysis. The porous network showed a very large
active surface area and significantly increased the adsorption capacity which can
reach 49.6pmol/cm2. Moreover, the immunoaffinity sorbent showed good sturdiness
at least 10 times with stable extraction performance. Once the main experimental
parameters were optimized, the method was used to detect DES, HES and DIS in
environmental water samples. The limits of detection for the three estrogens were
0.05-0.15ng/mL, and the limits of quantification was 0.5ng/mL. The average
recoveries ranged from 34.2 to 62.7% were achieved with good intra-day and inter
day precision ranging from 7.8 to 12.7% and from 8.2 to 13.5% respectively. The
newly developed immunoaffinity SPME showed high adsorption capacity, good
sensitivity and reproducibility and was successfully applied to the analysis of
DES, HES and DIS in environmental water samples.
PMID- 28704725
TI - Simultaneous estimation of lisofylline and pentoxifylline in rat plasma by high
performance liquid chromatography-photodiode array detector and its application
to pharmacokinetics in rat.
AB - Lisofylline (LSF) is an anti-inflammatory and immunomodulatory agent with proven
activity in serious infections associated with cancer chemotherapy, hyperoxia
induced acute lung injury, autoimmune disorders including type-1 diabetes (T1DM)
and islet rejection after islet transplantation. It is also an active metabolite
of another anti-inflammatory agent, Pentoxifylline (PTX). LSF bears immense
therapeutic potential in multiple pharmacological activities and hence
appropriate and accurate quantification of LSF is very important. Although a
number of analytical methods for quantification of LSF and PTX have been reported
for pharmacokinetics and metabolic studies, each of these have certain
limitations in terms of large sample volume required, complex extraction
procedure and/or use of highly sophisticated instruments like LC-MS/MS. The aim
of current study is to develop a simple reversed-phase HPLC method in rat plasma
for simultaneous determination of LSF and PTX with the major objective of
ensuring minimum sample volume, ease of extraction, economy of analysis,
selectivity and avoiding use of instruments like LC-MS/MS to ensure a widespread
application of the method. A simple liquid-liquid extraction method using
methylene chloride as extracting solvent was used for extracting LSF and PTX from
rat plasma (200MUL). Samples were then evaporated, reconstituted with mobile
phase and injected into HPLC coupled with photo-diode detector (PDA). LSF, PTX
and 3-isobutyl 1-methyl xanthine (IBMX, internal standard) were separated on
Inertsil(r) ODS (C18) column (250*4.6mm, 5MUm) with mobile phase consisting of A
methanol B-water (50:50v/v) run in isocratic mode at flow rate of 1mL/min for
15min and detection at 273nm. The method showed linearity in the concentration
range of 50-5000ng/mL with LOD of 10ng/mL and LLOQ of 50ng/mL for both LSF and
PTX. Weighted linear regression analysis was also performed on the calibration
data. The mean absolute recoveries were found to be 80.47+/-3.44 and 80.89+/
3.73% for LSF and PTX respectively. The method was successfully applied for
studying the pharmacokinetics of LSF and PTX after IV bolus administration at
dose of 25mg/kg in Wistar rat. In conclusion, a simple, sensitive, accurate and
precise reversed-phase HPLC-UV method was established for simultaneous
determination of LSF and PTX in rat plasma.
PMID- 28704726
TI - BNIP3 induction by hypoxia stimulates FASN-dependent free fatty acid production
enhancing therapeutic potential of umbilical cord blood-derived human mesenchymal
stem cells.
AB - Mitophagy under hypoxia is an important factor for maintaining and regulating
stem cell functions. We previously demonstrated that fatty acid synthase (FASN)
induced by hypoxia is a critical lipid metabolic factor determining the
therapeutic efficacy of umbilical cord blood-derived human mesenchymal stem cells
(UCB-hMSCs). Therefore, we investigated the mechanism of a major mitophagy
regulator controlling lipid metabolism and therapeutic potential of UCB-hMSCs.
This study revealed that Bcl2/adenovirus E1B 19kDa protein-interacting protein 3
(BNIP3)-dependent mitophagy is important for reducing mitochondrial reactive
oxygen species accumulation, anti-apoptosis, and migration under hypoxia. And,
BNIP3 expression was regulated by CREB binding protein-mediated transcriptional
actions of HIF-1alpha and FOXO3. Silencing of BNIP3 suppressed free fatty acid
(FFA) synthesis regulated by SREBP1/FASN pathway, which is involved in UCB-hMSC
apoptosis via caspases cleavage and migration via cofilin-1-mediated F-actin
reorganization in hypoxia. Moreover, reduced mouse skin wound-healing capacity of
UCB-hMSC with hypoxia pretreatment by BNIP3 silencing was recovered by palmitic
acid. Collectively, our findings suggest that BNIP3-mediated mitophagy under
hypoxia leads to FASN-induced FFA synthesis, which is critical for therapeutic
potential of UCB-hMSCs with hypoxia pretreatment.
PMID- 28704727
TI - NRF2 deficiency replicates transcriptomic changes in Alzheimer's patients and
worsens APP and TAU pathology.
AB - Failure to translate successful neuroprotective preclinical data to a clinical
setting in Alzheimer's disease (AD) indicates that amyloidopathy and tauopathy
alone provide an incomplete view of disease. We have tested here the relevance of
additional homeostatic deviations that result from loss of activity of
transcription factor NRF2, a crucial regulator of multiple stress responses whose
activity declines with ageing. A transcriptomic analysis demonstrated that NRF2
KO mouse brains reproduce 7 and 10 of the most dysregulated pathways of human
ageing and AD brains, respectively. Then, we generated a mouse that combines
amyloidopathy and tauopathy with either wild type (AT-NRF2-WT) or NRF2-deficiency
(AT-NRF2-KO). AT-NRF2-KO brains presented increased markers of oxidative stress
and neuroinflammation as well as higher levels of insoluble phosphorylated-TAU
and Abeta*56 compared to AT-NRF2-WT mice. Young adult AT-NRF2-KO mice exhibited
deficits in spatial learning and memory and reduced long term potentiation in the
perforant pathway. This study demonstrates the relevance of normal homeostatic
responses that decline with ageing, such as NRF2 activity, in the protection
against proteotoxic, inflammatory and oxidative stress and provide a new strategy
to fight AD.
PMID- 28704728
TI - Development of a novel multiplexed qPCR and Pyrosequencing method for the
detection of human pathogenic yersiniae.
AB - The purpose of this study was to develop a novel and robust molecular assay for
the detection of human pathogenic yersiniae (i.e. Yersinia enterocolitica, Y.
pseudotuberculosis and Y. pestis) in complex food samples. The assay combines
multiplexed real-time PCR (qPCR) and Pyrosequencing for detecting and
differentiating human pathogenic yersiniae with high confidence through sequence
based confirmation. The assay demonstrated 100% specificity and inclusivity when
tested against a panel of 14 Y. enterocolitica, 22 Y. pestis, 24 Y.
pseudotuberculosis and a diverse selection of 17 other non-Yersinia bacteria.
Pyrosequencing reads ranged from 28 to 40bp in length and had 94-100% sequence
identity to the correct species in the GenBank nr database. Microbial enrichments
of 48 ready-to-eat foods collected in the Greater Toronto Area from March 2014 to
May 2014, including 46 fresh sprout and 2 salad products, were then tested using
the assay. All samples were negative for Y. pestis and Y. pseudotuberculosis.
Both salads (n=2) and 35% of sprout products (n=46) including 7.1% of alfalfa
sprouts (n=14), 81% of bean sprouts (n=16), 12% of mixed sprouts (n=8) tested
positive for Y. enterocolitica which was not detected in broccoli sprouts (n=5),
onion sprouts (n=1), and pea sprouts (n=2). Cycle thresholds (Ct) of positive
samples for Y. enterocolitica were between 23.0 and 37.9 suggesting post
enrichment concentrations of approximately 1*102 to 1*106Y. enterocolitica per
1mL of enriched broth. An internal amplification control which was coamplified
with targets revealed PCR inhibition in five samples which was resolved following
a one in ten dilution. Pyrosequencing of qPCR amplicons suggests monoclonality
and revealed a single nucleotide polymorphism that is present in Y.
enterocolitica biotype 1A suggesting low pathogenicity of the detected strains.
This study is the first to combine Pyrosequencing and qPCR for the detection of
human pathogenic yersiniae and is applicable to a broad range of complex samples
including ready-to-eat food samples.
PMID- 28704729
TI - Longitudinal association between physical activity engagement during adolescence
and mental health outcomes in young adults: A 21-year birth cohort study.
AB - OBJECTIVE: Previous studies provide mixed evidence that physical activity
engagement (PAE) in adolescence is associated with later mental health outcomes.
This study aimed to examine the association between PAE at age 14 and mental
health outcomes at age 21 using a large birth cohort study. MATERIAL AND METHODS:
Prospective data from the Mater-University of Queensland Study of Pregnancy,
consisting of 3493 young adults, were analyzed. PAE at age 14 was estimated using
self-report, and participants were categorized into; (1) frequent, (2)
infrequent, or (3) no PAE group. Mental health outcomes at age 21 consisted of;
(1) common mental disorders, (2) psychosis-related outcomes, and, (3) emotional
and behavioral problems. The association between PAE in adolescence and later
mental health outcomes in young adulthood was examined using logistic regression,
adjusted for age, sex, body mass index, and adolescent psychopathology. RESULTS:
No PAE at age 14 was associated with the increased likelihood of lifetime
diagnosis of any affective disorder, elevated delusional ideation, and
endorsement of visual perceptual disturbance at age 21. Conversely, infrequent
PAE at age 14 was associated with the decreased likelihood of subsequent lifetime
diagnosis of any substance use disorder. CONCLUSION: Our findings suggest that
lack of PAE in adolescence influences some, but not all, later mental health
outcomes. Interventions to increase PAE in adolescence may represent an
opportunity to prevent future mental health problems.
PMID- 28704730
TI - Consistent patterns of vehicle collision risk for six mammal species.
AB - The occurrence and rate of wildlife-vehicle collisions are related to both
anthropocentric and environmental variables, however, few studies compare
collision risks for multiple species within a model framework that is adaptable
and transferable. Our research compares collision risk for multiple species
across a large geographic area using a conceptually simple risk framework. We
used six species of native terrestrial mammal often involved with wildlife
vehicle collisions in south-east Australia. We related collisions reported to a
wildlife organisation to the co-occurrence of each species and a threatening
process (presence and movement of road vehicles). For each species, we
constructed statistical models from wildlife atlas data to predict occurrence
across geographic space. Traffic volume and speed on road segments (also
modelled) characterised the magnitude of threatening processes. The species
occurrence models made plausible spatial predictions. Each model reduced the
unexplained variation in patterns and distributions of species between 29.5%
(black wallaby) and 34.3% (koala). The collision models reduced the unexplained
variation in collision event data between 7.4% (koala) and 19.4% (common ringtail
possum) with predictor variables correlating similarly with collision risk across
species. Road authorities and environmental managers need simple and flexible
tools to inform projects. Our model framework is useful for directing mitigation
efforts (e.g. on road effects or species presence), predicting risk across
differing spatial and temporal scales and target species, inferring patterns of
threat, and identifying areas warranting additional data collection, analysis,
and study.
PMID- 28704731
TI - Random forests as cumulative effects models: A case study of lakes and rivers in
Muskoka, Canada.
AB - Cumulative effects assessment (CEA) - a type of environmental appraisal - lacks
effective methods for modeling cumulative effects, evaluating indicators of
ecosystem condition, and exploring the likely outcomes of development scenarios.
Random forests are an extension of classification and regression trees, which
model response variables by recursive partitioning. Random forests were used to
model a series of candidate ecological indicators that described lakes and rivers
from a case study watershed (The Muskoka River Watershed, Canada). Suitability of
the candidate indicators for use in cumulative effects assessment and watershed
monitoring was assessed according to how well they could be predicted from
natural habitat features and how sensitive they were to human land-use. The best
models explained 75% of the variation in a multivariate descriptor of lake
benthic-macroinvertebrate community structure, and 76% of the variation in the
conductivity of river water. Similar results were obtained by cross-validation.
Several candidate indicators detected a simulated doubling of urban land-use in
their catchments, and a few were able to detect a simulated doubling of
agricultural land-use. The paper demonstrates that random forests can be used to
describe the combined and singular effects of multiple stressors and natural
environmental factors, and furthermore, that random forests can be used to
evaluate the performance of monitoring indicators. The numerical methods
presented are applicable to any ecosystem and indicator type, and therefore
represent a step forward for CEA.
PMID- 28704732
TI - Prioritizing conservation areas for coastal plant diversity under increasing
urbanization.
AB - Coastal urban expansion will continue to drive further biodiversity losses, if
conservation targets for coastal ecosystems are not defined and met. Prioritizing
areas for future protected area networks is thus an urgent task in such
urbanization-threatened ecosystems. Our aim is to quantify past and future losses
of coastal vegetation priority areas due to urbanization and assess the
effectiveness of the existing protected area network for conservation. We conduct
a prioritization analysis, based on 82 coastal plants, including common and IUCN
red list species, in a highly-urbanized but biotically diverse region, in South
Eastern France. We evaluate the role of protected areas, by taking into account
both strict and multi-use areas. We assess the impact of past and future
urbanization on high priority areas, by combining prioritization analyses and
urbanization models. We show that half of the highly diverse areas have already
been lost due to urbanization. Remaining top priority areas are also among the
most exposed to future urban expansion. The effectiveness of the existing
protected area (PA) network is only partial. While strict PAs coincide well with
top priority areas, they only represent less than one third of priority areas.
The effectiveness of multi-use PAs, such as the Natura 2000 network, also remains
limited. Our approach highlights the impact of urbanization on plant conservation
targets. By modelling urbanization, we manage to identify those areas where
protection could be more efficient to limit further losses. We suggest to use our
approach in the future to expand the PA network in order to achieve the 2020
Aichi biodiversity targets.
PMID- 28704733
TI - Reversal of long term potentiation-like plasticity in primary motor cortex in
patients with progressive supranuclear palsy.
AB - OBJECTIVE: Abnormal primary motor cortex plasticity might be involved in the
pathophysiology of progressive supranuclear palsy. In the present study we aimed
to investigate possible abnormalities of depotentiation, a mechanism involved in
plasticity regulation, in this condition. METHODS: Primary motor cortex
excitability, investigated with single and paired-pulse transcranial magnetic
stimulation, as well as long-term potentiation-like plasticity and its
reversibility, were studied using theta burst stimulation in 15 patients with
progressive supranuclear palsy and 11 healthy controls. Participants underwent
two sessions using (1) the intermittent theta-burst stimulation (potentiation
protocol) and (2) intermittent theta-burst stimulation combined with a
depotentiation protocol (a short continuous theta-burst stimulation). RESULTS:
Patients with PSP had higher corticospinal excitability and lower intracortical
inhibition than healthy controls. Intermittent theta-burst stimulation elicited
an abnormally increased long term potentiation-like effect in patients in
comparison to healthy subjects. However, the depotentiation protocol was able to
reverse the effects intermittent theta-burst stimulation on motor cortex
excitability both in patients and in healthy controls. CONCLUSIONS: Altered
primary motor cortex plasticity in patients with PSP does not reflect an
abnormality of depotentiation. SIGNIFICANCE: This study provides information for
a deeper understanding of the possible pathophysiological mechanisms underlying
the altered M1 plasticity in PSP.
PMID- 28704734
TI - Metacognition of agency is reduced in high hypnotic suggestibility.
AB - A disruption in the sense of agency is the primary phenomenological feature of
response to hypnotic suggestions but its cognitive basis remains elusive. Here we
tested the proposal that distorted volition during response to suggestions arises
from poor metacognition pertaining to the sources of one's control. Highly
suggestible and control participants completed a motor task in which performance
was reduced through surreptitious manipulations of cursor lag and stimuli speed.
Highly suggestible participants did not differ from controls in performance or
metacognition of performance, but their sense of agency was less sensitive to
cursor lag manipulations, suggesting reduced awareness that their control was
being manipulated. These results indicate that highly suggestible individuals
have aberrant metacognition of agency and may be a valuable population for
studying distortions in the sense of agency.
PMID- 28704735
TI - Successful voluntary recruitment of cognitive control under acute stress.
AB - In highly complex task situations (dual tasking), stressed individuals have been
shown to adapt the most resource-efficient task processing strategy, accepting
costs of performance. We argue that an interpretation of this behavior in terms
of a stress-induced impairment of cognitive control might be too simplified. In
the present study, we therefore tested whether stressed individuals are still
capable to up-regulate cognitive control when instructed to adapt more resource
intensive strategies, enabling preservation of task performance. Fifty-six
participants underwent either an established psychosocial stress induction
protocol (Trier Social Stress Test) or a standardized control intervention.
Afterwards, all participants performed a dual task in which task prioritization
was systematically varied, calling for the adoption of different task processing
strategies that require more or less voluntary top-down control. Although
individuals of the stress group showed a pronounced stress response, as indicated
by salivary cortisol, they were able to recruit more resources and to engage more
voluntary top-down control when instructed to do so. This finding suggests an
adaptive nature of control regulation under acute stress that reflects a
compensatory capacity with the potential to account for some of the observed
ostensible impairments of cognitive control. Our finding calls for careful
empirical examination of whether stressed individuals cannot or do not recruit
certain cognitive control functions in a given situation that will inform novel
interventions to optimize performance in high-stress environments.
PMID- 28704736
TI - Investigating co-combustion characteristics of bamboo and wood.
AB - To investigate co-combustion characteristics of bamboo and wood, moso bamboo and
masson pine were torrefied and mixed with different blend ratios. The combustion
process was examined by thermogravimetric analyzer (TGA). The results showed the
combustion process of samples included volatile emission and oxidation combustion
as well as char combustion. The main mass loss of biomass blends occurred at
volatile emission and oxidation combustion stage, while that of torrefied biomass
occurred at char combustion stage. With the increase of bamboo content,
characteristic temperatures decreased. Compared with untreated biomass, torrefied
biomass had a higher initial and burnout temperature. With the increase of
heating rates, combustion process of samples shifted to higher temperatures.
Compared with non-isothermal models, activation energy obtained from isothermal
model was lower. The result is helpful to promote development of co-combustion of
bamboo and masson pine wastes.
PMID- 28704737
TI - Biosurfactant-enhanced hydrogen production from organic fraction of municipal
solid waste using co-culture of E. coli and Enterobacter aerogenes.
AB - The effect of biosurfactants (surfactin and saponin) on the hydrogen production
from organic fraction of municipal solid waste (OFMSW) was investigated using co
culture of facultative anaerobes Enterobacter aerogenes and E. coli. The
biosurfactants were applied in the concentration ranges of 0.5, 1.0, 1.5, 2.0,
2.5, 3.0, 3.5 and 5.0% each. Cumulative hydrogen production (P), maximum hydrogen
production rate (Rmax) and lag phases (lambda) were analyzed using modified
Gompertz model. Results revealed that both the biosurfactants were effective in
hydrogen production enhancement. The maximum cumulative hydrogen production of
743.5+/-14.4ml and 675.6+/-12.1ml and volumetric hydrogen production of
2.12LH2/Lsubstrate and 1.93LH2/Lsubstrate was recorded at 3.5% surfactin and 3.0%
saponin respectively. Corresponding highest hydrogen yields were
79.2mlH2/gCarboinitial and 72.0mlH2/gCarboinitial respectively. Lag phase
decreased from 12.5+/-2.0h at control to a minimum of 9.0+/-2.8h and 9.5+/-2.1h
at 3.5% surfactin and 3.0% saponin respectively. Volatile fatty acid generation
was increased with biosurfactants addition.
PMID- 28704738
TI - High efficiency microbial electrosynthesis of acetate from carbon dioxide by a
self-assembled electroactive biofilm.
AB - Microbial electrosynthesis (MES) is a biocathode-driven process, producing high
value chemicals from CO2. Here, an in situ self-assembled graphene oxide
(rGO)/biofilm was constructed, in MES, for high efficient acetate production. GO
has been successfully reduced by electroautotrophic bacteria for the first time.
An increase, of 1.5 times, in the volumetric acetate production rate, was
obtained by self-assembling rGO/biofilm, as compared to the control group. In MES
with rGO/biofilm, a volumetric acetate production rate of 0.17gl-1d-1 has been
achieved, 77% of the electrons consumed, were recovered and the final acetate
concentration reached 7.1gl-1, within 40days. A three-dimensional rGO/biofilm was
constructed enabling highly efficient electron transfer rates within biofilms,
and between biofilm and electrode, demonstrating that the development of 3D
electroactive biofilms, with higher extracellular electron transfer rates, is an
effective approach to improving MES efficiency.
PMID- 28704739
TI - Efficient harvesting of marine Chlorella vulgaris microalgae utilizing cationic
starch nanoparticles by response surface methodology.
AB - Harvesting involves nearly thirty percent of total production cost of microalgae
that needs to be done efficiently. Utilizing inexpensive and highly available
biopolymer-based flocculants can be a solution for reducing the harvest costs.
Herein, flocculation process of Chlorella vulgaris microalgae using cationic
starch nanoparticles (CSNPs) was evaluated and optimized through the response
surface methodology (RSM). pH, microalgae and CSNPs concentrations were
considered as the main independent variables. Under the optimum conditions of
microalgae concentration 0.75gdry weight/L, CSNPs concentration 7.1mgdry weight/L
and pH 11.8, the maximum flocculation efficiency (90%) achieved. Twenty percent
increase in flocculation efficiency observed with the use of CSNPs instead of the
non-particulate starch which can be due to the more electrostatic interactions
between the cationic nanoparticles and the microalgae. Therefore, the synthesized
CSNPs can be employed as a convenient and economical flocculants for efficient
harvest of Chlorella vulgaris microalgae at large scale.
PMID- 28704740
TI - Comparative assessment of selected sugarcane biorefinery-centered systems in
Brazil: A multi-criteria method based on sustainability indicators.
AB - This work proposes a new sustainability assessment framework aiming to compare
selected options of biorefineries subject to provide the same services to a
community. At this end, a concept of biorefinery-centered system helps to develop
a joint resources and policy-oriented comparison. When an option of biorefinery
cannot provide the given amounts of certain services from its own production, it
complements its supply portfolio by purchasing the lacking amounts from
complementary and conventional production systems. The proposed sustainability
assessment framework includes a multi-criteria method used to compare the
selected biorefinery options resulting in identifying their respective weaknesses
and strengths against categories of criteria. Finally, the methodology helps
finding the non-dominated option. Application to selected sugarcane-based
biorefineries shows promising results that match with those obtained in a
previous work. However, the new methodology allows extended and richer analyses.
PMID- 28704741
TI - Outside the box: Medications worth considering when traditional antiepileptic
drugs have failed.
AB - PURPOSE: Review and discuss medications efficacious for seizure control, despite
primary indications for other diseases, as treatment options in patients who have
failed therapy with traditional antiepileptic drugs (AEDs). METHODS: Literature
searches were conducted utilizing PubMed and MEDLINE databases employing
combinations of search terms including, but not limited to, "epilepsy",
"refractory", "seizure", and the following medications: acetazolamide,
amantadine, bumetanide, imipramine, lidocaine, verapamil, and various stimulants.
RESULTS: Data from relevant case studies, retrospective reviews, and available
clinical trials were gathered, analyzed, and reported. Experience with
acetazolamide, amantadine, bumetanide, imipramine, lidocaine, verapamil, and
various stimulants show promise for cases of refractory epilepsy in both adults
and children. Many medications lack large scale, randomized clinical trials, but
the available data is informative when choosing treatment for patients that have
failed traditional epilepsy therapies. CONCLUSIONS: All neurologists have
encountered a patient that failed nearly every AED, diet, and surgical option.
For these patients, we often seek fortuitous discoveries within small series and
case reports, hoping to find a treatment that might help the patient. In the
present review, we describe medications for which antiepileptic effect has been
ascribed after they were introduced for other indications.
PMID- 28704742
TI - Q10R mutation in SCN9A gene is associated with generalized epilepsy with febrile
seizures plus.
PMID- 28704743
TI - Sleep abnormalities in juvenile myoclonic epilepsy-A sleep questionnaire and
polysomnography based study.
AB - PURPOSE: To evaluate the quality of sleep, its architecture and occurrence of
epileptiform discharges with their distribution across various stages of sleep in
patients of Juvenile myoclonic epilepsy (JME), both drug naive as well as those
already on treatment. METHODS: 99 patients of JME [36 drug naive, 63 on
antiepileptic drug(s) (AED)], and 30 healthy controls were recruited. Sleep
quality and daytime sleepiness were evaluated with Pittsburgh Sleep Quality Index
(PSQI) and Epworth Sleepiness Scale (ESS), respectively.Polysomnography (PSG) was
done to assess the sleep architecture. The EDI (Epileptiform Discharge Index) per
stage of sleep was calculated. RESULTS: JME patients had significantly poor
quality of sleep by PSQI (p=0.02).PSG revealed reduced sleep efficiency
[p<0.001], increased sleep latency [p=0.02], increased%WASO [p<0.001],
increased%N1 [p=0.01] and decreased% REM sleep [p=0.002] in the patients compared
to controls. Epileptiform discharges were frequent among drug naive JME patients
[drug naive, 868 vs. 727, treatment group]. EDI was higher in N1 (p=0.001) and N2
(p=0.007) in drug naive compared to JME patients on treatment. EDI in valproate
treatment group was relatively lower to other AEDs. CONCLUSION: JME is associated
with poor sleep quality and altered architecture, irrespective of treatment
status. REM sleep is significantly decreased in JME patients. Epileptiform
discharges are frequent in lighter NREM sleep and EDI is higher in drug naive
patients. Although AEDs disrupt the NREM sleep, their use is associated with
arousal stability in lighter stages of sleep and lower EDI, in particular with
valproate.
PMID- 28704744
TI - A primary intraosseous cystic meningioma: Case report.
AB - INTRODUCTION: This is a very rare case of intraosseous cystic meningioma. There
have been no reports of similar cases in the last 30 years. PRESENTATION OF CASE:
A 62-year-old man, suffering from a swelling of the lateral wall of the left
orbit was admitted to our hospital. MRI and CT scan showed a large intradiploic
lesion involving the lateral wall of the orbit and the greater wing of the
sphenoid. The lesion was cystic with a mural nodule. We operated the patient and
removed completely the mural nodule and the fibrous wall of cyst. Histological
examination showed that the mural nodule was a benign meningothelial meningioma.
DISCUSSION: Primary intraosseous meningiomas represent a subtype of primary
extradural meningiomas; they comprise about 2% of all meningiomas and are
therefore rare entities. Cystic meningiomas are rare, their incidence compared to
all other types of meningiomas is of 2-4%. The presence of a meningioma with both
characteristics: cystic and intraosseous, like in our case, is an exceptional
occurrence. CONCLUSION: The surgical management of tumor was easy; its rarity
means that the case is interesting.
PMID- 28704745
TI - Giant iatrogenic pseudoaneurysm of the brachial artery: A case report.
AB - INTRODUCTION: Pseudoaneurysms are a pulsatile hematoma caused by hemorrhage on
soft tissues. It is an uncommon condition with many different etiologies. We
report a case of a giant pseudoaneurysm caused by iatrogenic injury on the
brachial artery. PRESENTATION OF CASE: A 42 year-old male was submitted to our
Vascular Surgery service with an enlargement of the right upper limb and a
history of myocardial infarction. 60days before the patient reached our service,
he was submitted to a cardiac catheterization performed by another medical team,
since the catheter was placed on the right brachial artery near the cubital
fossa, we suspected an iatrogenic pseudoaneurysm, which was confirmed by his
clinical history and physical exam. It was opted to treat the pseudoaneurysm with
an implant of polytetrafluoroethylene prosthesis. There were no complications
whatsoever and the patient was discharged. DISCUSSION: Pseudoaneurysms are more
common after interventional procedures than diagnostic procedures, although
brachial artery pseudoaneurysms are rare. Complications of pseudoaneurysms can
cause serious threat to the afflicted limb and the patient's life. The management
of any pseudoaneurysm is dependent on its size, location and pathogenesis.
CONCLUSION: Pseudoaneurysms develop slowly and should be diagnosed as early as
possible in order to avoid complications and a better outcome. Due to an increase
in recent endovascular procedures and the fact that brachial artery puncture is
being performed more routinely, incidence of brachial artery pseudoaneurysms
among overall population may rise.
PMID- 28704746
TI - A case report of an anterior tibial artery pseudo-aneurysm open surgical
management: A rare complication post total knee arthroplasty.
AB - INTRODUCTION: Complications involving injury to neurological and vascular
structures are infrequently reported after total knee arthroplasty (TKA). They
are associated with significant morbidity and can be limb threatening.
PRESENTATION OF CASE: We present a patient with an anterior tibial artery (ATA)
aneurysm post total knee arthroplasty. A 69-year-old female was referred for a
swelling over her left antero-lateral aspect of her leg 4 years post TKA.
Radiological investigations showed an ATA pseudo aneurysm. The aneurysm was
repaired by open ligation. DISCUSSION: ATA pseudo aneurysm is a rare condition
post arthroplasty. Patients can complain about calf pain, digits discoloration,
paresthesia and the presence of a pulsating or enlarging mass. Symptomatic
aneurysms require surgical intervention. CONCLUSION: ATA pseudo aneurysms are
uncommon. They are usually identified shortly after the initial insult. A delayed
manifestation of a post knee arthroplasty complication as illustrated in our case
is likely the first reported case of its kind. Clinicians should maintain a high
index of suspicion should there be persistent localised swelling post TKA.
However, due to the rarity of this condition, a variety of interventions have
been reported in the English medical literature with probably no compelling
evidence that favors one modality over the others.
PMID- 28704747
TI - Two cases of late medial instability of the knee due to hip disease after total
knee arthroplasty.
AB - INTRODUCTION: There are few specific reports of late medial instability after
total knee arthroplasty (TKA). We described two cases of late medial instability
of the knee due to hip disease with osteoarthritis or rheumatoid arthritis after
TKA, which required revision TKA. PRESENTATION OF CASES: An 82-year-old woman
experienced right femoral neck fracture due to a fall that required conservative
treatment at age 77 years and underwent left TKA at age 80 years. A 68-year-old
woman underwent left TKA at age 54 years, right TKA at age 64 years, and left THA
at age 67 years. Both cases required revision TKA with constrained knee
prostheses due to the severe medial instability. Hip-knee-ankle (HKA) angle,
range of motion (ROM), Knee Society score (KSS) and functional score (FS) were
evaluated pre- and postoperatively. Their respective HKA angle improved from 134
degrees and 155 degrees preoperatively to 184 degrees and 179 degrees
postoperatively. KSS improved from -4 and 53 points to 59 and 100 points,
respectively. FS improved from -10 and 58 points to 25 and 90 points,
respectively. In the 82-year-old woman, ROM did not improve from -10-90 degrees
to -20-90 degrees . On the other hand, in the 68-year-old woman, ROM improved
from 0-110 degrees to 0-125 degrees . The late medial instability in the current
case report was partly due to a similar mechanism underlying the long leg
arthropathy and coxitis knee caused by hip joint degeneration. CONCLUSIONS:
Constrained prostheses were applied for both patients, providing moderately good
short-term results.
PMID- 28704748
TI - Clinicopathological features of breast angiosarcoma: A 16-years single
institution experience.
AB - BACKGROUND: Breast Angiosarcoma is a rare type of malignancy arising from
endothelial cells lining blood vessels, accounting for 1% of all soft tissue
breast tumors. This retrospective study describes the clinical pathological
features and clinical management and outcomes of a series of 5 patients with
primary and secondary Angiosarcoma of the breast present to King Faisal Specialty
Hospital and Research Center during the last 16 years. METHODS: A retrospective
review of our institution's pathology database was conducted and all patients who
had a pathologically confirmed breast angiosarcoma were included in this study.
The patient's data, including demographic characteristics, pathological features,
clinical management history and clinical outcomes were collected. RESULTS: Five
patients were diagnosed with Breast Angiosarcoma (one secondary and four primary
cases). The median age of patients with primary angiosarcoma was 22 years (range
13-25 years). All primary cases were presented late as post-excisional biopsy at
local hospitals. Median tumor size was 6cm (range 4.0-17.0cm). All primary
angiosarcoma patients had total mastectomy. Three-year disease-free survival
(DFS) of patients with primary angiosarcoma was 25%. 5-year surviving rate of
primary angiosarcoma was 50%. Recurrence was observed in three of the patients
with primary Angiosarcoma and in the case of post irradiation Angiosarcoma.
CONCLUSIONS: Our study demonstrates that Breast Angiosarcoma exhibits high
recurrence and mortality rates. Early detection, small tumor size, and clear
surgical margins seem to be crucial factors for survival. Mastectomy with
adequate tumor margin is recommended and close long-term follow-up is of utmost
importance. Surgery for local recurrence may be potentially curative.
PMID- 28704749
TI - Key role of the sorption process in alteration of metal and metalloid
quantification by fouling development on DGT passive samplers.
AB - The DGT technique (diffusive gradients in thin films) is widely used for passive
sampling of labile trace metals and metalloids in natural waters. Although
development of fouling on the protective membranes is frequently observed, its
effect on DGT sampling has been barely investigated. This study evaluates the
influence of fouling on sampling of trace cationic metals Cd(II), Cu(II), Ni(II)
and Pb(II) and oxyanions As(V), Cr(VI), Sb(V) and Se(VI). Fouling was developed
in situ on polycarbonate membranes in four diverse natural freshwater
environments and sampling alteration was assessed in controlled laboratory
experiments. Accumulation of oxyanions and Ni was unaltered in the presence of
fouling whereas significant alteration occurred in sampling of Cd, Cu and Pb (at
pH ~5.4). Characterization of the fouled membranes highlighted the intervention
of sorption phenomenon as sampling alteration was systematically observed
alongside element sorption onto fouled membrane. A preliminary flowchart for
identifying potentially biased quantifications linked to fouling development
during in situ DGT deployment in natural waters is proposed.
PMID- 28704750
TI - Homing pigeons externally exposed to Deepwater Horizon crude oil change flight
performance and behavior.
AB - The Deepwater Horizon oil spill was the largest in U.S. history, contaminating
thousands of miles of coastal habitat and affecting the lives of many avian
species. The Gulf of Mexico is a critical bird migration route area and migrants
that were oiled but did not suffer mortality as a direct result of the spill
faced unpredictable fates. This study utilized homing pigeons as a surrogate
species for migratory birds to investigate the effects a single low level
external oiling event has on the flight performance and behavior of birds flying
repeated 161 km flights. Data from GPS data loggers showed that lightly oiled
pigeons changed their flight paths, increased their flight durations by 2.6 fold,
increased their flight distances by 28 km and subsequently decreased their route
efficiencies. Oiled birds also exhibited reduced rate of weight gain between
flights. Our data suggest that contaminated birds surviving the oil spill may
have experienced flight impairment and reduced refueling abilities, likely
reducing overall migration speed. Our findings contribute new information on how
oil spills affect avian species, as the effects of oil on the flight behavior of
long distance free-flying birds have not been previously described.
PMID- 28704751
TI - Protective effect of ferulic acid on cisplatin induced nephrotoxicity in rats.
AB - This study aims to determine the potential protective effects of ferulic acid
against cisplatin-induced nephrotoxicity and to compare its effect with curcumin,
a well-known protective agent against cisplatin- induced toxicity in rats.
Administration of cisplatin resulted in high BUN (Blood Urea Nitrogen),
creatinine, MDA (Malondialdehyde), MPO (Myeloperoxidase), TOS (Total Oxidative
Status), PtNT (Protein Nitrotyrosine) levels (p<0.05). Histological observations
showed abnormal morphology of kidney; in addition with appearance of TUNEL
positive cells indicating apoptosis in cisplatin administered group. HO-1 (Heme
Oxygenase-1) levels measured by RT-PCR (Real Time Polymerase Chain Reaction), and
TAS (Total Antioxidative Status) revealed antioxidant depletion due to cisplatin
toxicity in animals (p<0.05). All parameters showed improvement in groups treated
with ferulic acid (p<0.05). Ferulic acid treatment was found significant in
preventing oxidative stress, increasing antioxidative status and regaining
histological parameters to normal, indicating nephroprotective and antioxidant
effects of this phenolic compound.
PMID- 28704752
TI - Assessing human metal accumulations in an urban superfund site.
AB - Butte, Montana is part of the largest superfund site in the continental United
States. Open-pit mining continues in close proximity to Butte's urban population.
This study seeks to establish baseline metal concentrations in the hair and blood
of individuals living in Butte, MT and possible routes of exposure. Volunteers
from Butte (n=116) and Bozeman (n=86) were recruited to submit hair and blood
samples and asked to complete a lifestyle survey. Elemental analysis of hair and
blood samples was performed by ICP-MS. Three air monitors were stationed in Butte
to collect particulate and filters were analyzed by ICP-MS. Soil samples from the
yards of Butte volunteers were quantified by ICP-MS. Hair analysis revealed
concentrations of Al, As, Cd, Cu, Mn, Mo, and U to be statistically elevated in
Butte's population. Blood analysis revealed that the concentration of As was also
statistically elevated in the Butte population. Multiple regression analysis was
performed for the elements As, Cu, and Mn for hair and blood samples. Soil
samples revealed detectable levels of As, Pb, Cu, Mn, and Cd, with As and Cu
levels being higher than expected in some of the samples. Air sampling revealed
consistently elevated As and Mn levels in the larger particulate sampled as
compared to average U.S. ambient air data.
PMID- 28704753
TI - Resveratrol improves prostate fibrosis during progression of urinary dysfunction
in chronic prostatitis.
AB - AIM: We investigated whether prostate fibrosis was associated with urinary
dysfunction in chronic prostatitis (CP) and whether resveratrol improved urinary
dysfunction and the underlying molecular mechanism. METHODS: Rat model of CP was
established via subcutaneous injections of DPT vaccine and subsequently treated
with resveratrol. Bladder pressure and volume tests investigated the effect of
resveratrol on urinary dysfunction in CP rats. Western blotting and
immunohistochemical staining examined the expression level of C-kit/SCF and TGF
beta/Wnt/beta-catenin. RESULTS: Compared to the control group, the maximum
capacity of the bladder, residual urine volume and maximum voiding pressure, the
activity of C-kit/SCF and TGF-beta/Wnt/beta-catenin pathways were increased
significantly in the CP group. Resveratrol treatment significantly improved these
factors. CONCLUSION: CP induced significantly prostate fibrosis, which exhibits a
close relationship with urinary dysfunction. Resveratrol improved fibrosis, which
may be associated with the suppression of C-kit/SCF and TGF-beta/Wnt/beta-catenin
pathway.
PMID- 28704754
TI - Metabolomics study of cadmium-induced diabetic nephropathy and protective effect
of caffeic acid phenethyl ester using UPLC-Q-TOF-MS combined with pattern
recognition.
AB - Diabetic nephropathy (DN) is the most severe complication of diabetes and
multiple factors are involved in the pathogenesis of DN. Among them, cadmium (Cd)
acts as a risk factor inducing the occurrence of DN. The present study focused on
investigating the protective role of caffeic acid phenethyl ester (CAPE), an
active component of propolis from honeybee hives, against Cd-induced DN in mice
based on ultra performance liquid chromatography coupled with quadrupole time-of
flight mass spectrometry (UPLC-Q-TOF-MS)and pattern recognition. Serum and urine
biochemical indexes were detected and histopathological observation has been done
to evaluate the damage of Cd on animals. Moreover, the global serum profiles of
different groups were distinguished by UPLC-Q-TOF-MS and principal component
analysis (PCA) were applied for group differentiation and marker selection.
Moreover, the influence of Cd on the oxidative status in DN mice were also
evaluated by assessing the parameters of oxidative stress, proinflammatory
cytokines and antioxidant competence. As shown in the scores plots, the distinct
clustering among controls, DN and CAPE groups were observed, significant changes
in serum levels of LysoPC(18:1(11Z)), 2,3-dinor-8-iso-PGF2a,
PS(18:1(9Z)/18:1(9Z)), DG(17:0/22:4 (7Z,10Z, 13Z, 16Z)/0:0) and Arachidonic
acid(AA) were noted and identified as potential biomarkers, the effect of CAPE
reverted them back to near normalcy. Further, It was observed a significant
improvement in lipid peroxides (LPO) and protein carbonyls (PCO) levels in Cd
induced DN kidneys along with a significant decline in superoxide dismutase
(SOD), catalase (CAT), and reduced glutathione (GSH) levels, however, CAPE
relieved these changes. In conclusion, the study suggested that the pathogenesis
of DN caused by Cd probably owes to the perturbations of lipid metabolism and AA
metabolism; CAPE seems to be effective agent and may be related to its potent
antioxidant, anti-inflammatory properties and action as an Nrf2 activator.
PMID- 28704755
TI - Oral warfarin intake affects skin inflammatory cytokine responses in rats.
AB - Warfarin is an anticoagulant used in prevention/prophylaxis of thromboembolism.
Besides the effects on coagulation, non-hemorrhagic reactions have also been
documented. Although cutaneous reactions were reported in some patients, the
impact on skin immunity was not explored. In the present paper, the effect of 30
day oral warfarin intake on skin cytokine responses in rats was analyzed.
Increased release of inflammatory cytokines (TNF, IL-1beta and IL-10) was noted
by skin explants from rats which received warfarin, but without effect on IL-6.
No impact on epidermal cell cytokine secretion was seen, except a tendency of an
increase of IL-6 response to stimulation with microbial product
lipopolysaccharide (LPS). Topical application of contact allergen
dinitrochlorobenzene (DNCB) resulted in slight (numerical solely) increase of TNF
release by skin explants of warfarin-treated animals, while epidermal cells
responded by increased secretion of all four cytokines examined. The data
presented provide new information on the potential of oral warfarin to modulate
skin innate immune activity.
PMID- 28704756
TI - Protective role of dietary Spirulina platensis against diazinon-induced Oxidative
damage in Nile tilapia; Oreochromis niloticus.
AB - The current study was performed to investigate the ameliorating effect of dietary
supplementation of 0.5 and 1% Spiurolina platensis (SP) diet against the sub
acute toxicity of diazinon (DZN) 0.28mg/L in Nile tilapia. At the end of
experiment after 28days, hepatic and renal damage markers (aspartate
transaminase, alanine transaminase, alkaline phosphatase, urea, uric acid and
creatinine), serum biochemical parameters (total proteins, albumin, cholesterol
and glucose) and tissue antioxidant status (superoxide dismutase, catalase,
glutathione peroxidase, reduced glutathione and malondialdehyde) were
detesrmined. The results of the current study revealed significant improvement in
hepatic and renal damage markers after SP supplementation in fish exposed to DZN
toxicity. Moreover, SP improved serum biochemical markers through increasing
serum albumin and globulins with a significant decrease in serum glucose and
cholesterol. In addition, liver, kidneys and gills antioxidant status showed a
significant improvement after SP supplemented to fish exposed to DZN where a
significant increase in tissue antioxidant activity were observed with a
significant decline in lipid peroxidation levels. It can be concluded that, SP
supplementation attenuated the toxic effect of DZN toxicity in Nile tilapia
through improving liver and kidney functions with a significant enhancement of
tissue antioxidant status.
PMID- 28704757
TI - Structural optimization elaborates novel potent Akt inhibitors with promising
anticancer activity.
AB - Targeting of Akt has been validated as a well rationalized approach to cancer
treatment, and represents a promising therapeutic strategy for aggressive
hematologic malignancies. We describe herein an exploration of novel Akt
inhibitors for cancer therapy through structural optimization of previously
described 4-(piperazin-1-yl)-7H-pyrrolo[2,3-d]pyrimidine derivatives. Our studies
yielded a novel series of pyrrolopyrimidine based phenylpiperidine carboxamides
capable of potent inhibition of Akt1. Notably, 10h exhibited robust
antiproliferative effects in both mantle cell lymphoma cell lines and primary
patient tumor cells. Low micromolar doses of 10h induced cell apoptosis and cell
cycle arrest in G2/M phase, and significantly downregulated the phosphorylation
of Akt downstream effectors GSK3beta and S6 in Jeko-1 cells.
PMID- 28704758
TI - Deconstruction - reconstruction approach to analyze the essential structural
elements of tetrahydro-3-benzazepine-based antagonists of GluN2B subunit
containing NMDA receptors.
AB - The role of the phenolic and benzylic OH moieties for the interaction of
tetrahydro-3-benzazepine-1,7-diol 3d with GluN2B subunit containing NMDA
receptors was analyzed by their stepwise removal. Elimination of
trifluormethanesulfinate from 10 and 13 represent the key steps in the synthesis.
Removal of phenolic OH moiety led to 5-fold reduced GluN2B affinity of 4d
compared with 3d. Additional removal of the benzylic OH moiety (5d) resulted in
further reduced GluN2B affinity but increased sigma1 and sigma2 affinities.
Introduction of a NO2 (6d) or NH2 moiety (7d) decreased the GluN2B affinity. 3
Benzazepin-1-ol 4i with the N-phenylcyclohexyl side chain showed the highest
GluN2B affinity of this series of compounds (Ki = 2.2 nM) and, moreover, high
selectivity over the PCP binding site, sigma1 and sigma2 receptors. In docking
studies 3-benzazepines (S)-4-7 adopt the same binding poses as ifenprodil and
display the same crucial interactions. Unexpectedly, the high-affinity ligands
(S)-4i, (S)-4j, and (S)-6i were not able to inhibit the glutamate/glycine evoked
current in two-electrode voltage clamp measurements and the cytotoxic effects of
glutamate/glycine on transfected cell lines.
PMID- 28704759
TI - Novel pyrazolopyrimidines: Synthesis, in vitro cytotoxic activity and mechanistic
investigation.
AB - A series of novel pyrazolo[3,4-d]pyrimidines bearing benzenesulfonamide moiety 5a
f, 6 and 7 were synthesized. Cytotoxic screening was conducted against MCF-7 and
HepG2. 6-(4-Methoxyphenyl)-4-oxopyrazolopyrimidine derivative 5e and 4-imino-6
oxopyrazolopyrimidine derivative 6 revealed potent cytotoxic activity with IC50
1.4 MUM (MCF-7) and 0.4 MUM (HepG2), respectively compared to that of
doxorubicin, (IC50 = 1.02 MUM and 0.9 MUM, respectively). Compounds 5e and 6 were
subjected to cell cycle analysis and apoptosis assay after 24 h and 48 h
treatment. Compound 5e arrested cell at G1 phase, while 6 arrested cell at S and
G2/M phases, respectively. The apoptotic effect of both compounds were evidenced
by pre G1 apoptosis as its percentage increased by time (7.38%, 11.61%) and
(13.92%, 16.71%), respectively. Apoptosis induction capability was confirmed by
the effect on early and late apoptosis and augmentation of caspase-3 level.
Furthermore, compound 6 inhibited CDK2 enzyme with IC50 = 0.19 MUM and increased
levels of its regulators, P21 and P27 by 10.06% and 8.5%, respectively. Moreover,
a molecular docking study of compound 6 on CDK2 enzyme was adopted to explore
binding interaction with amino acid residues of its active site.
PMID- 28704760
TI - Synthesis and anti-oxidant activity evaluation of (+/-)-Anastatins A, B and their
analogs.
AB - Two novel flavonoids (+/-)-Anastatins A and B as well as 14 analogs, which
containing a benzofuran moiety, were synthesized by using halogenation, Suzuki
coupling reaction and an oxidation/Oxa-Michael reaction cascade as the key steps.
The structures of the new flavonoids were confirmed by 1H NMR, 13C NMR and HRMS.
The antioxidant activities of them as well as the key intermediates were
evaluated by ferric reducing antioxidant power (FRAP) assay and the active
compounds were evaluated in the PC12 cell model of hydrogen peroxide (H2O2)
induced oxidative damage. SAR studies suggested that, for in vitro antioxidant
activity, aurone derivatives showed better bioactivity than flavone counterparts.
However, cyclization to benzofuran and connecting the two conjugated parts as a
whole conjugated system by a double bond diminished the in vitro antioxidant
activity. Among them, the most potent compound 24c was significantly decreased
H2O2-caused cell injury. The apoptotic rate (Annexin V+) of H2O2-damaged PC12
cells was 60.7% while that of the compound 24c-treated cells decreased to 5.9%
and 4.1% at 10 MUM and 100 MUM respectively.
PMID- 28704761
TI - The association between specific combat experiences and aspects of the
Interpersonal Theory of Suicide.
AB - BACKGROUND: Studies examining the relationship between combat exposure and
suicide risk typically focus on combat exposure overall, combining numerous
different combat experiences. Our study expands upon prior research by examining
the association between specific combat experiences and components of both
suicidal desire and the capability for suicide. METHOD: We hypothesized that most
combat experiences would be associated with capability for suicide. Furthermore,
we hypothesized that experiences that involved direct exposure to death and
injury (e.g. personally witnessing the death or injury of other soldiers) would
be associated with higher levels of thwarted belongingness, perceived
burdensomeness, and suicidal ideation. Participants were 400 service members
drawn largely from the Army National Guard who had been deployed at least once
and endorsed having experienced combat. RESULTS: Consistent with hypotheses,
combat experiences involving direct exposure to injury or death exhibited a more
pronounced pattern of associations with suicide risk factors than did other
experiences. However, only a minority of combat experiences were associated with
the capability for suicide. DISCUSSION: These results, while preliminary,
indicate that different combat experiences are associated with different outcomes
and that, in this sense, not all combat experiences are created equal with
respect to suicide risk.
PMID- 28704762
TI - Combined Inhibition of CDK4/6 and PI3K/AKT/mTOR Pathways Induces a Synergistic
Anti-Tumor Effect in Malignant Pleural Mesothelioma Cells.
AB - Malignant pleural mesothelioma (MPM) is a progressive malignancy associated to
the exposure of asbestos fibers. The most frequently inactivated tumor suppressor
gene in MPM is CDKN2A/ARF, encoding for the cell cycle inhibitors p16INK4a and
p14ARF, deleted in about 70% of MPM cases. Considering the high frequency of
alterations of this gene, we tested in MPM cells the efficacy of palbociclib (PD
0332991), a highly selective inhibitor of cyclin-dependent kinase (CDK) 4/6. The
analyses were performed on a panel of MPM cell lines and on two primary culture
cells from pleural effusion of patients with MPM. All the MPM cell lines, as well
as the primary cultures, were sensitive to palbociclib with a significant
blockade in G0/G1 phase of the cell cycle and with the acquisition of a senescent
phenotype. Palbociclib reduced the phosphorylation levels of CDK6 and Rb, the
expression of myc with a concomitant increased phosphorylation of AKT. Based on
these results, we tested the efficacy of the combination of palbociclib with the
PI3K inhibitors NVP-BEZ235 or NVP-BYL719. After palbociclib treatment, the
sequential association with PI3K inhibitors synergistically hampered cell
proliferation and strongly increased the percentage of senescent cells. In
addition, AKT activation was repressed while p53 and p21 were up-regulated.
Interestingly, two cycles of sequential drug administration produced irreversible
growth arrest and senescent phenotype that were maintained even after drug
withdrawal. These findings suggest that the sequential association of palbociclib
with PI3K inhibitors may represent a valuable therapeutic option for the
treatment of MPM.
PMID- 28704763
TI - Symptoms of anxiety and depression in type 2 diabetes: Associations with clinical
diabetes measures and self-management outcomes in the Norwegian HUNT study.
AB - OBJECTIVE: To determine if symptoms of depression and anxiety are differentially
associated with clinical diabetes measures and self-management behaviours in
individuals with Type 2 diabetes, and whether these associations vary by patient
sex. RESEARCH DESIGN AND METHODS: A cross-sectional analysis using data from 2035
adults with Type 2 diabetes in the Nord-Trondelag Health Study. Multivariate
logistic regression was used to explore associations between symptoms of
depression and anxiety and waist girth, HDL cholesterol, systolic blood pressure,
triglycerides, c-reactive protein, glycemic control, diet adherence, exercise,
glucose monitoring, foot checks for ulcers, and the subjective patient
experience. Analyses were stratified by sex. RESULTS: Depression was associated
with a lower likelihood of avoiding saturated fats (OR=0.20 [95% CI: 0.06, 0.68])
and increased odds of physical inactivity (OR=1.69 [95% CI: 1.37, 2.72]). Anxiety
was associated with increased odds of eating vegetables (OR=1.66 [95% CI: 1.02,
2.73]), and an over two-fold increase of feeling that having diabetes is
difficult. In women, anxiety was associated with elevated c-reactive protein
levels (OR=1.57 [95% CI: 1.05, 2.34]). In men, depressive symptoms were
associated with elevated HbA1c (OR=5.00 [95% CI: 1.15, 8.23). CONCLUSIONS:
Symptoms of depression and anxiety were differentially associated with some key
diabetes-related measures. Our results suggest sex-specific differences with
respect to two important clinical outcomes (i.e., anxiety and CRP in women and
depression and glycemic control in men). These findings should alert
practitioners to the importance of detection and management of psychological
symptoms in individuals with Type 2 diabetes.
PMID- 28704764
TI - Logical empiricists on race.
AB - The logical empiricists expressed a consistent attitude to racial categorisation
in both the ethical and scientific spheres. Their attitude may be captured in the
following slogan: human racial taxonomy is an empirically meaningful mode of
classifying persons that we should refrain from deploying. I offer an
interpretation of their position that would render coherent their remarks on race
with positions they adopted on the scientific status of taxonomy in general,
together with their potential moral or political motivations for adopting that
position.
PMID- 28704765
TI - High-intensity drinking and nonmedical use of prescription drugs: Results from a
national survey of 12th grade students.
AB - BACKGROUND: Nearly 10% of U.S. 12th graders report high-intensity drinking (10+
or 15+ drinks in a row), but the extent to which these drinkers also engage in
nonmedical use of prescription drugs (NMUPD) is largely unknown. This study
examined the associations between different thresholds of past two-week high
intensity drinking and past-month NMUPD among U.S. 12th graders. METHODS: The
sample consisted of eleven nationally representative cross-sections of 12th
graders in the Monitoring the Future study (2005-2015) who answered questions on
past two-week drinking behaviors and past-month nonmedical use of prescription
opioids, sedative, stimulants, and tranquilizers (N=26,502 respondents). RESULTS:
High-intensity drinking during the past two-weeks was associated with an
increased risk of past-month NMUPD. The odds of NMUPD were four times larger
among 12th graders who indicated drinking 15 or more drinks on at least one
occasion (AOR=4.43, 95% CI=3.18, 5.01) relative to those who had 0-4 drinks
during the past two-weeks, after adjusting for relevant covariates. These
associations were similar across different classes of prescription drugs and
tended to be stronger among non-white respondents. A sub-analysis revealed
simultaneous co-ingestion of alcohol and NMUPD was more prevalent among high
intensity drinkers. CONCLUSIONS: More than 1 in every 4 U.S 12th graders who
engage in high-intensity drinking (15+ drinks in a row) also report NMUPD. Given
the greater likelihood of simultaneous co-ingestion of alcohol and prescription
drugs among high-intensity drinkers, adolescent substance use interventions need
to address the risks associated with mixing alcohol and prescription drugs.
PMID- 28704766
TI - Differential effects of perceived stress on alcohol consumption in moderate
versus heavy drinking HIV-infected women.
AB - OBJECTIVE: To examine the association between perceived stress and subsequent
alcohol use in women living with HIV. METHODS: Women (n=338) receiving HIV care
between April 2006 and July 2010 who enrolled in either a brief intervention for
hazardous drinking or a cohort of non-hazardous drinkers completed a 90-day
drinking and drug use history, and completed stress, depression and anxiety
measures at 0, 6, and 12 months. We examined the association between perceived
stress at months 0 or 6 and measures of quantity and frequency of alcohol use in
months 3-6 and 9-12, respectively. RESULTS: The association between perceived
stress and subsequent alcohol use depended on whether women were heavy or
moderate drinkers at index visit. Among women reporting >=7 drinks/week at index
visit, high levels of perceived stress were associated with subsequent increased
alcohol intake. However, among women reporting >0 but <7 drinks/week at index
visit, high levels of perceived stress were associated with a subsequent
reduction in drinking. CONCLUSIONS: Baseline drinking status moderates the
relationship between perceived stress and subsequent alcohol use. Perceived
stress is an important therapeutic target in women who are heavy drinkers.
PMID- 28704767
TI - Ibudilast may improve attention during early abstinence from methamphetamine.
AB - BACKGROUND: Inattention is a deficit related to instilling abstinence from
methamphetamine (MA) dependence. This study aimed to determine whether ibudilast
(IB; 50mg bid) improves attentional abilities compared to placebo during early
abstinence from MA dependence. METHODS: Attention was assessed in 11 MA-dependent
non-treatment seeking participants in a phase IB safety-interaction trial. The
Conners' Continuous Performance Test-II (CPT-II), a measure of sustained
attention and response inhibition, was administered at baseline and on day 22,
48h post a MA challenge under placebo (P; n=6) or IB 50mg bid (n=5). Group
differences were compared using Mann-Whitney U Tests. Groups were similar at
baseline in premorbid intellectual functioning, attention deficit hyperactivity
symptom scores, impulsivity ratings, and education level, but differed in age.
Demographically corrected T-scores for CPT-II performances were utilized.
RESULTS: Although no group differences in sustained attention existed at
baseline, at follow-up, the IB group (Mdn=44.4) showed reduced variability in
response times compared with the P group (Mdn=69.9), U=0.00, z=-2.74, p=.006,
r=.83. The IB group (Mdn=45.8) also gave fewer perseverative responses than the P
group (Mdn=67.0), U=2.00, z=-2.50, p=.01, r=.75. No other significant differences
were observed. CONCLUSIONS: Findings suggest that IB may have a protective effect
on sustained attention during early abstinence from MA dependence. This may guide
thinking about mechanism of action should IB demonstrate efficacy as a treatment
for MA dependence.
PMID- 28704768
TI - Impact of e-liquid flavors on nicotine intake and pharmacology of e-cigarettes.
AB - OBJECTIVES: To describe the effect of e-liquid flavors on nicotine intake and
pharmacology of e-cigarettes. METHODS: 11 males and 3 females participated in a 3
day inpatient crossover study with strawberry, tobacco, and their usual flavor e
liquid. Nicotine levels were nominally 18mg/mL in the strawberry (pH 8.29) and
tobacco (pH 9.10) e-liquids and ranged between 3-18mg/mL in the usual brands
(mean pH 6.80). Each day consisted of a 15-puff session followed by 4h of
abstinence, then 90min of ad libitum use. Subjects used a KangerTech mini ProTank
3. RESULTS: After 15 puffs, the amount of nicotine inhaled and systemically
retained were not significantly different between the strawberry and tobacco e
liquids but plasma AUC(0->180) was significantly higher with the strawberry e
liquid. While not significantly different, Cmax was 22% higher and various early
time point AUCs to measure rate of rise of nicotine in blood ranged between 17
and 23% higher with the strawberry e-liquid compared to the tobacco e-liquid.
During ad libitum use, systemic exposure to nicotine (AUC(0->90)) was the same
for the tobacco and usual brand e-liquids but were both significantly lower than
after using the strawberry e-liquid. The usual flavors were more liked and
satisfying than the strawberry and tobacco e-liquids. CONCLUSION: Flavors
influence nicotine exposure through flavor liking, may affect rate of nicotine
absorption possibly through pH effects, and contribute to heart rate acceleration
and subjective effects of e-cigarettes. E-cigarette users titrate their nicotine
exposure but the extent of titration may vary across flavors.
PMID- 28704769
TI - Characterizing marijuana concentrate users: A web-based survey.
AB - AIMS: The study seeks to characterize marijuana concentrate users, describe
reasons and patterns of use, perceived risk, and identify predictors of
daily/near daily use. METHODS: An anonymous web-based survey was conducted (April
June 2016) with 673 US-based cannabis users recruited via the Bluelight.org web
forum and included questions about marijuana concentrate use, other drugs, and
socio-demographics. Multivariable logistic regression analyses were conducted to
identify characteristics associated with greater odds of lifetime and daily use
of marijuana concentrates. RESULTS: About 66% of respondents reported marijuana
concentrate use. The sample was 76% male, and 87% white. Marijuana concentrate
use was viewed as riskier than flower cannabis. Greater odds of marijuana
concentrate use was associated with living in states with "recreational"
(AOR=4.91; p=0.001) or "medical, less restrictive" marijuana policies (AOR=1.87;
p=0.014), being male (AOR=2.21, p=0.002), younger (AOR=0.95, p<0.001), number of
other drugs used (AOR=1.23, p<0.001), daily herbal cannabis use (AOR=4.28,
p<0.001), and lower perceived risk of cannabis use (AOR=0.96, p=0.043). About 13%
of marijuana concentrate users reported daily/near daily use. Greater odds of
daily concentrate use was associated with being male (AOR=9.29, p=0.033), using
concentrates for therapeutic purposes (AOR=7.61, p=0.001), using vape pens for
marijuana concentrate administration (AOR=4.58, p=0.007), and lower perceived
risk of marijuana concentrate use (AOR=0.92, p=0.017). CONCLUSIONS: Marijuana
concentrate use was more common among male, younger and more experienced users,
and those living in states with more liberal marijuana policies. Characteristics
of daily users, in particular patterns of therapeutic use and utilization of
different vaporization devices, warrant further research with community-recruited
samples.
PMID- 28704770
TI - Detection of oncogenic viruses in water environments by a Luminex-based multiplex
platform for high throughput screening of infectious agents.
AB - Recent studies documented the detection of viruses strongly associated with human
cancer in urban sewages and other water environments worldwide. The aim of this
study was to estimate the occurrence of human oncogenic viruses in environmental
samples (sewage, river, marine, and pool/spa water) using highly sensitive and
specific multiplex bead-based assays (Luminex technology). A total of 33 samples
were analysed for 140 oncogenic viral agents, including mucosal and cutaneous
human papillomaviruses (HPVs), human polyomaviruses (HPyV), human herpesviruses
(HHV) and mouse mammary tumour virus (MMTV). Eighty-eight percent of the samples
tested positive for at least one viral pathogen and the simultaneous presence of
more than one virus was frequent (mean number of positivities/sample = 3.03). A
total of 30 different Alpha, Beta and Gamma HPVs were detected, including mucosal
and cutaneous types. The high-risk type HPV16 was the most frequently detected
virus, identified in 73% of the samples. Of the 12 HPyVs tested, only two (BKPyV
and MCPyV) were detected. At least one of these two was present in 48% of the
samples. MMTV was detected in 21% of the samples, while herpesviruses - HHV-6 and
HHV-1 - were detected in two samples (6%). The present study is the first to
provide a comprehensive picture of the occurrence of oncogenic viruses belonging
to different families and species in diverse water environments, and the first to
successfully use, in environmental samples, a Luminex-based multiplex platform
for high throughput screening of infectious agents. Our findings, showing that
oncogenic viruses are ubiquitous in water environments, pave the way for future
studies on the fate of these pathogens in water environments as well as on their
potential for transmission via the waterborne route.
PMID- 28704771
TI - Predicting the propagation of concentration and saturation fronts in fixed-bed
filters.
AB - The phenomenon of adsorption is widely exploited across a range of industries to
remove contaminants from gases and liquids. Much recent research has focused on
identifying low-cost adsorbents which have the potential to be used as
alternatives to expensive industry standards like activated carbons. Evaluating
these emerging adsorbents entails a considerable amount of labor intensive and
costly testing and analysis. This study proposes a simple, low-cost method to
rapidly assess the potential of novel media for potential use in large-scale
adsorption filters. The filter media investigated in this study were low-cost
adsorbents which have been found to be capable of removing dissolved phosphorus
from solution, namely: i) aluminum drinking water treatment residual, and ii)
crushed concrete. Data collected from multiple small-scale column tests was used
to construct a model capable of describing and predicting the progression of
adsorbent saturation and the associated effluent concentration breakthrough
curves. This model was used to predict the performance of long-term, large-scale
filter columns packed with the same media. The approach proved highly successful,
and just 24-36 h of experimental data from the small-scale column experiments
were found to provide sufficient information to predict the performance of the
large-scale filters for up to three months.
PMID- 28704772
TI - Assessing the role of bed sediments in the persistence of red mud pollution in a
shallow lake (Kinghorn Loch, UK).
AB - Red mud is a by-product of alumina production. Little is known about the long
term fate of red mud constituents in fresh waters or of the processes regulating
recovery of fresh waters following pollution control. In 1983, red mud leachate
was diverted away from Kinghorn Loch, UK, after many years of polluting this
shallow and monomictic lake. We hypothesised that the redox-sensitive
constituents of red mud leachate, phosphorus (P), arsenic (As) and vanadium (V),
would persist in the Kinghorn Loch for many years following pollution control as
a result of cycling between the lake bed sediment and the overlying water column.
To test this hypothesis, we conducted a 12-month field campaign in Kinghorn Loch
between May 2012 and April 2013 to quantify the seasonal cycling of P, As, and V
in relation to environmental conditions (e.g., dissolved oxygen (DO)
concentration, pH, redox chemistry and temperature) in the lake surface and
bottom waters. To confirm the mechanisms for P, As and V release, a sediment core
incubation experiment was conducted using lake sediment sampled in July 2012, in
which DO concentrations were manipulated to create either oxic or anoxic
conditions similar to the bed conditions found in the lake. The effects on P, As,
and V concentrations and species in the water column were measured daily over an
eight-day incubation period. Phosphate (PO4-P) and dissolved As concentrations
were significantly higher in the bottom waters (75.9 +/- 30.2 MUg L-1 and 23.5 +/
1.83 MUg L-1, respectively) than in the surface waters (12.9 +/- 1.50 MUg L-1
and 14.1 +/- 2.20 MUg L-1, respectively) in Kinghorn Loch. Sediment release of As
and P under anoxic conditions was confirmed by the incubation experiment and by
the significant negative correlations between DO and P and As concentrations in
the bottom waters of the lake. In contrast, the highest dissolved V
concentrations occurred in the bottom waters of Kinghorn Loch under oxic
conditions (15.0 +/- 3.35 MUg L-1), with the release from the bed sediment
apparently being controlled by a combination of competitive ion concentrations,
pH and redox conditions.
PMID- 28704773
TI - The influence of protruding filamentous bacteria on floc stability and solid
liquid separation in the activated sludge process.
AB - Filamentous bacteria can impact on the physical properties of flocs in the
activated sludge process assisting solid-liquid separation or inducing problems
when bacteria are overabundant. While filamentous bacteria within the flocs are
understood to increase floc tensile strength, the relationship between protruding
external filaments, dewatering characteristics and floc stability is unclear.
Here, a quantitative methodology was applied to determine the abundance of
filamentous bacteria in activated sludge samples from four wastewater treatment
plants. An automated image analysis procedure was applied to identify filaments
and flocs and calculate the length of the protruding filamentous bacteria (PFB)
relative to the floc size. The correlation between PFB and floc behavior was then
assessed. Increased filament abundance was found to increase interphase drag on
the settling flocs, as quantified by the hindered settling function.
Additionally, increased filament abundance was correlated with a lower gel point
concentration leading to poorer sludge compactability. The floc strength factor,
defined as the relative change in floc size upon shearing, correlated positively
with filament abundance. This influence of external protruding filamentous
bacteria on floc stability is consistent with the filamentous backbone theory,
where filamentous bacteria within flocs increase floc resistance to shear-induced
breakup. A qualitative correlation was also observed between protruding and
internal filamentous structure. This study confirms that filamentous bacteria are
necessary to enhance floc stability but if excessively abundant will adversely
affect solid-liquid separation. The tools developed here will allow quantitative
analysis of filament abundance, which is an improvement on current qualitative
methods and the improved method could be used to assist and optimize the
operation of waste water treatment plants.
PMID- 28704774
TI - Corrosion protection products as a source of bisphenol A and toxicity to the
aquatic environment.
AB - Steel components are typically treated with anti-corrosion coatings like epoxy or
polyurethane resins to protect the integrity and functioning of steel. Such
resins may contain substances, such as bisphenol A (BPA), that have caused
concern in a human and environmental toxicological context. We investigated the
release of toxicity from four anti-corrosion coatings used in hydraulic and civil
engineering. Resins were applied onto glass plates and leachate samples produced
by horizontally shaking the plates in water for 7 days. Two experiments were
conducted, one with a 1 day and one with a 7 day curing period. Using a suite of
bioassays, we tested samples for: agonistic and antagonistic effects on various
mammalian nuclear receptors; inhibition of photosynthesis and growth in algae;
inhibition of bacterial bioluminescence; and inhibition of water flea
reproduction. Concentrations of BPA, bisphenol F and various BPA transformation
products were determined by chemical analysis (LC-MS/MS). Bioassay results were
evaluated using a scheme developed by DIBt (Centre of Competence for
Construction, Berlin, Germany). Three products induced responses in one or more
of the measured endpoints and toxicity profiles varied markedly in intensity
across products. One product released high amounts of BPA which was associated
with effects on nuclear receptor transactivation, requiring a more than 700-fold
dilution for effect induction to fall below 20%. The same product was also the
most toxic to water flea reproduction, requiring ca. 70-fold dilution for effects
to fall below 20%. Another product was highly toxic in terms of bacterial
bioluminescence, particularly after a shorter curing time, requiring a ca. 1'300
fold dilution for effects to fall below 20%. The third product required a 22-fold
dilution for inhibition of water flea reproduction to drop below 20%. Results
show that anti-corrosion coatings based on epoxy resins can be a source of
toxicity to the aquatic environment. The fact that some products are more toxic
than others highlights opportunities for the development of low risk formulations
and products with better environmental performance. Finally, the DIBt scheme
provides a useful starting point to develop further ecotoxicity guidelines for
testing and data evaluation of leachates from construction materials.
PMID- 28704775
TI - Evaluating the reinforcement content and elastic properties of Mg-based
composites using dual-mode ultrasonic velocities.
AB - Based on the wave-mode-converted principle, an immersion-focused transducer is
employed to determine the longitudinal wave and shear wave velocities. The
experimental condition is then investigated to obtain the converted shear wave,
which is used to analyze the relationship between the reinforcement content and
the dual-mode ultrasonic velocities. In addition, the elastic modulus is
calculated. Magnesium-based composite samples with different reinforcement
contents are manufactured to conduct an ultrasonic experiment, wherein the dual
mode velocities vary with the change in the reinforcement content; the
correlation coefficient is 99.17%. An ultrasonic dual-mode velocity model is
developed to analyze the distribution of the reinforcement content. By employing
the measured values obtained from the destructive method, the largest errors in
the reinforcement content and elastic modulus evaluated using the proposed method
are found to be -5.76% and 5.85%, respectively. The shear wave velocity
determined using a normal-incidence shear-wave transducer reveals the accuracy
with which the errors are measured. This method provides an effective tool to
nondestructively evaluate the microstructure and elastic properties of Mg-based
composites.
PMID- 28704776
TI - Structural dynamics of wild type and mutated forms of human L1 endonuclease and
insights into its sequence specific nucleic acid binding mechanism: A molecular
dynamics study.
AB - Biomolecular recognition of proteins and nucleic acids is mainly mediated by
their structural features and the molecular dynamics simulations approach has
been used to explore this recognition processes at the atomic level. L1
Endonuclease, an enzyme involved in L1 retrotransposition, cleaves the TA
junction DNA (5'-TTTT/AA-3') and expresses high specificity for target site
recognition. The present study highlights the structural features of L1
endonuclease as well as DNA responsible for such specific recognition.
Especially, the importance of betaB6-B5 hairpin loop in DNA recognition has been
elucidated by analyzing the dynamics of Thr192 mutated L1-endonuclease. In
addition, simulations of the endonuclease complexed with DNA substrates
(sequences having TA and CG junctions) revealed the specificity of L1
endonuclease towards TA junction. Molecular dynamics simulations revealed that
the betaB6-B5 hairpin loop protrudes well into the minor groove of DNA having TA
junction and induces DNA bending such that the width of minor groove is
increased. Such endonuclease induced bending of TA junction DNA sequence
positions the scissile phosphodiester bond of DNA for cleavage. The innate
property of minor groove widening in TA junction than in CG junction is utilized
by the betaB6-betaB5 hairpin loop of endonuclease while recognizing the DNA
sequences. The present study also highlights the role of Mg2+ cation in catalysis
and attempts to explore the possible target site DNA cleavage mechanism.
PMID- 28704777
TI - Preinvasive disease of the airway.
AB - Squamous cell carcinoma of the lung arises from preinvasive progenitors in the
central airways. The archetypal model appears to be a stepwise morphological
progression until there is invasion of the basement membrane. However, not every
lesion appears to follow this course and many individuals can have stable
disease, or indeed regress to normal epithelium. From our increased understanding
of the molecular pathology it is becoming apparent that the respiratory
epithelium accumulates progressive genetic and epigenetic insults in response to
carcinogens. Still, little is known about how to predict those 'at risk' of
progression, and it is likely that in the future molecular signatures will
underpin prediction models of developing invasive lung cancer. Currently,
autofluorescence bronchoscopy gives us the ability to follow the natural history
of these lesions, with the prospect that detecting and treating lesions early may
improve survival. However, treatment remains controversial, and radical therapies
are offered to individuals with carcinoma in situ who may never develop invasive
cancer. This has paved the way for the use of minimally invasive bronchoscopic
treatments, which, while apparently effective, have not been tested in randomised
controlled trials. In this paper we describe the known biology and natural
history of preinvasive lesions and review the current treatment strategies.
PMID- 28704778
TI - Eradication of Helicobacter pylori infection might improve clinical status of
patients with Parkinson's disease, especially on bradykinesia.
AB - OBJECTIVES: Previous studies have shown that Helicobacter pylori infection might
make clinical status worse in patients with Parkinson's disease and Helicobacter
pylori eradication might improve clinical status by modifying the
pharmacokinetics of L-dopa. Here, we investigate whether Helicobacter pylori
eradication could benefit idiopathic parkinsonism and Helicobacter pylori
infection will effect which aspect of motor symptom significantly. PATIENTS AND
METHODS: A cohort study involving idiopathic Parkinson's disease patients,
screened for Helicobacter status by 13C urea breath test. Clinical status was
evaluated by using the Unified Parkinson's Disease Rating Scale (UPDRS) and Hoehn
Yahr stage. If patients had motor complications, they were quantified at the "on"
time. The Helicobacter pylori positive patients could choose to receive
Helicobacter pylori eradication or not by themselves. Group 1 was Helicobacter
pylori negative patients. Group 2 was Helicobacter pylori positive patients who
didn't receive eradication treatment. Group 3 was Helicobacter pylori positive
patients who received successful eradication treatment. Repeat clinical
assessments and 13C urea breath test was performed at 1year later. Numerical data
were expressed as mean+/-standard deviation (SD) RESULTS: Ninety-four consecutive
patients with Parkinson's disease were recruited and underwent the initial 13C
urea breath test, but only forty-eight patients successfully completed the total
study. In Group 3, the UPDRS-III scores (=Motor Examination Section Scores) were
significantly lower 1year later compared to baseline (18.3+/-8.38 vs. 25.9+/
8.37, P=0.007). The differences were main in UPDRS-23 (=Finger Taps) (1.7+/-1.16
vs. 2.4+/-1.51, P=0.045), UPDRS-25 (Rapid Alternation Movements of Hands) (1.6+/
1.35 vs. 2.4+/-1.71, P=0.031) and UPDRS-26 (=Leg Agility) (1.3+/-1.25 vs.2.1+/
0.99, P=0.011). There was difference among three groups in the UPDRS-26 (P=0.040)
of clinical status change of one year. CONCLUSION: The eradication of
Helicobacter might improve the clinical status of idiopathic parkinsonism,
especially on bradykinesia.
PMID- 28704779
TI - Circulating miR-128 as a potential diagnostic biomarker for glioma.
AB - OBJECTIVE: miR-128 in circulation is a promising marker for early diagnosis of
glioma. A meta-analysis was performed to evaluate the diagnostic accuracy and
clinical value of circulating miR-128 in patients with glioma. MATERIALS AND
METHODS: A comprehensive literature search for relevant published articles (last
search updated on December 29, 2016) was conducted in the Chinese Biomedical
Literature Database, PubMed, and Embase. The quality assessment of diagnostic
accuracy studies (QUADAS) tool was used to score the quality of the eligible
studies. Meta-Disc 1.4 software was used to test for heterogeneity and to perform
the meta-analysis. RESULTS: The three studies included in our study enrolled a
total of 191 patients with glioma and 73 individuals without tumor. Using a fixed
effect model analysis, the summary assessments revealed that the pooled
sensitivity, specificity, positive likelihood ratio, and negative likelihood
ratio were 0.89 (95% CI: 0.84-0.93), 0.90 (95% CI: 0.81-0.96), 8.07 (95% CI: 4.21
15.46), and 0.13 (95% CI: 0.09-0.19), respectively. The diagnostic odds ratio
(DOR) of miR-128 was 65.00 (95% CI: 26.90-157.10), indicating that the overall
accuracy of the miR-128 test for detecting glioma was high. The value of I2 was
0.0%, indicating that there was no significant heterogeneity among studies.
CONCLUSION: The present meta-analysis showed that circulating miR-128 might be a
promising noninvasive biomarker for diagnosing glioma.
PMID- 28704780
TI - Acceleration of blood flow as an indicator of improved hemodynamics after
indirect bypass surgery in Moyamoya disease.
AB - OBJECTIVE: The ultrasonography findings in the superficial temporal artery (STA)
in Moyamoya disease patients treated with indirect bypass remain unclear. We
evaluated the time-related changes in ultrasonography findings of the STA main
trunk and branches in patients with Moyamoya disease who underwent encephalo-duro
arterio-synangiosis (EDAS). PATIENTS AND METHODS: Patients (n=21, 30 sides) with
Moyamoya disease who underwent EDAS at Fukuoka University Hospital were
prospectively registered between 2008 and 2015. EDAS using the frontal and
parietal branches of the STA was adopted in an indirect bypass procedure. Mean
velocity (MV) and resistance index (RI) were used as ultrasonography markers, and
their changes over time in the STA main trunk and branches were assessed.
RESULTS: There was a significant increase in MV in both the STA main trunk
(p=0.001) and branches (frontal: p=0.005, parietal: p=0.003) at 3 months after
EDAS, whereas there was a decrease in RI at 14days after EDAS (main trunk: p
<0.001, frontal: p <0.001, parietal: p=0.014). In subgroup analysis of patients
divided by EDAS outcome, compared with before EDAS, there were significant
differences at 3 months after EDAS in MV (responders: main trunk: p=0.002,
frontal: p=0.001, parietal: p=0.001; non-responders: main trunk: p=0.093,
frontal: p=0.24, parietal: p=0.96) and RI (responders: main trunk: p<0.001,
frontal: p<0.001, parietal: p=0.006; non-responders: main trunk: p=0.17, frontal:
p=0.12, parietal: p=0.17). CONCLUSIONS: Measurement of MV may be useful for
predicting outcome at 3 months after EDAS.
PMID- 28704781
TI - Impacts of EGFR mutation and EGFR-TKIs on incidence of brain metastases in
advanced non-squamous NSCLC.
AB - OBJECTIVE: Brain metastases remain lethal in lung cancer patients. The impacts of
epidermal growth factor receptor (EGFR) mutations and EGFR tyrosine kinase
inhibitors (TKIs) on the incidence of brain metastases in patients with advanced
non-squamous non-small cell lung cancer (NSCLC) are still uncertain. PATIENTS AND
METHODS: A total of 1672 patients with advanced non-squamous NSCLC with a
definitive report on EGFR mutation status between January 2005 and June 2013 were
retrospectively analyzed. The impacts of EGFR mutation status and EGFR TKIs use
on the incidence of brain metastases and survival were investigated. RESULTS: Of
the 1672 patients, 465 (27.8%) had an EGFR mutation, and 1207 (72.2%) did not.
Four hundred and eighteen (25.0%) patients had baseline brain metastases. The
cumulative incidence of brain metastases for patients in EGFR+ group was
significantly higher than patients in EGFR- group (HR, 1.27; 95% CI 1.06-1.52;
P=0.008). The cumulative incidence of brain metastases was also higher for
patients who received an EGFR-TKI as their first-line treatment than those who
received other first-line treatment (HR, 1.36; 95% CI 1.14-1.64; P=0.001).
Patients harboring EGFR mutations had prolonged overall survival (OS) than
patients with wild-type EGFR (HR, 0.47; 95% CI 0.41-0.54; P<0.001; median, 25.2
vs. 12.9 months). CONCLUSIONS: Both the EGFR mutation-positive status and the use
of a TKI are associated with higher incidence of brain metastases for patients
with advanced non-squamous NSCLC.
PMID- 28704782
TI - Electrochemical DNA biosensor based on grafting-to mode of terminal
deoxynucleoside transferase-mediated extension.
AB - Previously reported electrochemical DNA biosensors based on in-situ
polymerization approach reveal that terminal deoxynucleoside transferase (TdTase)
has good amplifying performance and promising application in the design of
electrochemical DNA biosensor. However, this method, in which the background is
significantly affected by the amount of TdTase, suffers from being easy to
produce false positive result and poor stability. Herein, we firstly present a
novel electrochemical DNA biosensor based on grafting-to mode of TdTase-mediated
extension, in which DNA targets are polymerized in homogeneous solution and then
hybridized with DNA probes on BSA-based DNA carrier platform. It is surprising to
find that the background in the grafting-to mode of TdTase-based electrochemical
DNA biosensor have little interference from the employed TdTase. Most
importantly, the proposed electrochemical DNA biosensor shows greatly improved
detection performance over the in-situ polymerization approach-based
electrochemical DNA biosensor.
PMID- 28704783
TI - Biomass-derived heteroatoms-doped mesoporous carbon for efficient oxygen
reduction in microbial fuel cells.
AB - Currently, the development of less expensive, more active and more stable
catalysts like heteroatom-doped carbon based non-precious metal materials are
highly desired for the cathodic oxygen reduction reaction (ORR) in microbial fuel
cells (MFCs). Comparing with heteroatom sources from chemical reagents, biomass
is notably inexpensive and abundant, containing more elements which contribute to
ORR activity. Herein, we demonstrate an easy operating one-step and low-cost way
to synthesize egg-derived heteroatoms-doped mesoporous carbon (EGC) catalysts
utilizing egg as the biomass carbon and other elements source (sulphur,
phosphorus, boron and iron), and porous g-C3N4 as both template and nitrogen
source. After carbonized, such hybrid materials possess an outstanding
electrocatalytic activity towards ORR comparable to the commercial Pt/C catalyst
in neutral media. Electrochemical detections as cyclic voltammogram and rotating
ring-disk electrode tests show that the potential of oxygen reduction peak of
EGC1-10-2 is at + 0.10V, onset potential is at + 0.257V (vs. Ag/AgCl) and
electron transfer number of that is 3.84-3.92, which indicate that EGC1-10-2 via
a four-electron pathway. Reactor operation shows that the maximum power density
of MFC-EGC1-10-2 (737.1mWm-2), which is slightly higher than MFC-Pt/C (20%)
(704mWm-2). The low cost (0.049 $g-1), high yield (20.26%) and high performance
of EGC1-10-2 provide a promising alternative to noble metal catalysts by using
abundant natural biological resources, which contribute a lot to expansion and
commercialization of MFCs.
PMID- 28704784
TI - Quantitative detection of glucose level based on radiofrequency patch biosensor
combined with volume-fixed structures.
AB - A concept for characterizing a radiofrequency (RF) patch biosensor combined with
volume-fixed structures is presented for timely monitoring of an individual's
glucose levels based on frequency variation. Two types of patch biosensors
separately integrated with a backside slot (0.53MUL) and a front-side tank
(0.70MUL) structure-were developed to achieve precise and efficient detection
while excluding the effects of interference due to the liquidity, shape, and
thickness of the tested glucose sample. A glucose test analyte at different
concentrations (50-600mg/dL) was dropped into the volume-fixed structures. It
fully interacted with the RF patch electromagnetic field, effectively and
sensitively changing the resonance frequency and magnitude of the reflection
coefficient. Measurement results based on the resonance frequency showed high
sensitivity up to 1.13MHz and 1.97MHz per mg/dL, and low detection limits of
26.54mg/dL and 15.22mg/dL, for the two types of patch biosensors, respectively,
as well as a short response time of less than 1s. Excellent reusability of the
proposed biosensors was verified through three sets of measurements for each
individual glucose sample. Regression analysis revealed a good linear correlation
between glucose concentrations and the resonance frequency shift. Moreover, to
facilitate a multi-parameter-sensitive detection of glucose, the magnitude of the
reflection coefficient was also tested, and it showed a good linear correlation
with the glucose concentration. Thus, the proposed approach can be adopted for
distinguishing glucose solution levels, and it is a potential candidate for early
stage detection of glucose levels in diabetes patients.
PMID- 28704785
TI - Detection of Ca2+-induced acetylcholine released from leukemic T-cells using an
amperometric microfluidic sensor.
AB - A microfluidic structured-dual electrodes sensor comprising of a pair of screen
printed carbon electrodes was fabricated to detect acetylcholine, where one of
them was used for an enzyme reaction and another for a detection electrode. The
former was coated with gold nanoparticles and the latter with a porous gold
layer, followed by electropolymerization of 2, 2:5,2-terthiophene-3-(p-benzoic
acid) (pTTBA) on both the electrodes. Then, acetylcholinesterase was covalently
attached onto the reaction electrode, and hydrazine and choline oxidase were co
immobilized on the detection electrode. The layers of both modified electrodes
were characterized employing voltammetry, field emission scanning electron
microscopy, X-ray photoelectron spectroscopy, and quartz crystal microscopy.
After the modifications of both electrode surfaces, they were precisely faced
each other to form a microfluidic channel structure, where H2O2 produced from the
sequential enzymatic reactions was reduced by hydrazine to obtain the analytical
signal which was analyzed by the detection electrode. The microfluidic sensor at
the optimized experimental conditions exhibited a wide dynamic range from 0.7nM
to 1500MUM with the detection limit of 0.6 +/- 0.1nM based on 3s (S/N = 3). The
biomedical application of the proposed sensor was evaluated by detecting
acetylcholine in human plasma samples. Moreover, the Ca2+-induced acetylcholine
released in leukemic T-cells was also investigated to show the in vitro detection
ability of the designed microfluidic sensor. Interference due to the real
component matrix were also studied and long term stability of the designed sensor
was evaluated. The analytical performance of the designed sensor was also
compared with commercially available ACh detection kit.
PMID- 28704786
TI - "Urinary incontinence secondary to amisulpride Use-A report".
PMID- 28704787
TI - Clinical characteristic of psychiatric symptoms in Acute Intermittent Porphyria
(AIP): A report of a pair of identical twins.
PMID- 28704788
TI - Effectiveness of clozapine for the treatment of psychosis and disruptive
behaviour in a child with Atypical Autism: A case report and a brief review of
the evidence.
PMID- 28704789
TI - Undergraduate students and psychiatry: Opening the pandora's box?
PMID- 28704790
TI - Pharmacological activities of an eye drop containing Matricaria chamomilla and
Euphrasia officinalis extracts in UVB-induced oxidative stress and inflammation
of human corneal cells.
AB - Ultraviolet B (UVB) exposure is a risk factor for corneal damage resulting in
oxidative stress, inflammation and cell death. The aim of this study was to
investigate the potential protective effects of a commercial eye drop
(DacriovisTM) containing Matricaria chamomilla and Euphrasia officinalis extracts
on human corneal epithelial cells (HCEC-12) against UVB radiation-induced
oxidative stress and inflammation as well as the underlying mechanisms. The
antioxidant potential of the eye drops was evaluated by measuring the ferric
reducing antioxidant power and the total phenolic content by Folin-Ciocalteu
reagent. HCEC-12 cells were exposed to UVB radiation and treated with the eye
drops at various concentrations. Cell viability, wound healing assay, reactive
oxygen species (ROS) levels, protein and lipid oxidative damage and COX-2, IL
1beta, iNOS, SOD-2, HO-1 and GSS gene expression, were assessed. Eye drops were
able to protect corneal epithelial cells from UVB-induced cell death and
ameliorated the wound healing; the eye drops exhibited a strong antioxidant
activity, decreasing ROS levels and protein and lipid oxidative damage. Eye drops
also exerted anti-inflammatory activities by decreasing COX-2, IL-1beta, iNOS
expression, counteracted UVB-induced GSS and SOD-2 expression and restored HO-1
expression to control levels. These findings suggest that an eye drop containing
Matricaria chamomilla and Euphrasia officinalis extracts exerts positive effects
against UVB induced oxidative stress and inflammation and may be useful in
protecting corneal epithelial cells from UVB exposure.
PMID- 28704791
TI - The association between discharge status, mental health, and substance misuse
among young adult veterans.
AB - Although 85% of military service members are discharged honorably, veterans who
engage in misconduct during military service may receive other types of
administrative or punitive discharges. The discharge type not only affects
eligibility for benefits, but is associated with negative downstream consequences
(e.g., homelessness, criminal justice involvement). However, limited empirical
research has examined the mental health and substance use-related needs of
veterans who were not Honorably discharged, and the few that have only focus on
veterans who received punitive discharges. This study addressed gaps in the
research literature on discharge status by examining differences in mental
health, substance use, and attitudes toward psychological treatment among
veterans who received Honorable, General Under Honorable Conditions, and Other
Than Honorable (OTH) discharges. Young adult veterans (N = 734) were recruited
online and completed a battery of self-report measures. Results indicated that
veterans who received General and OTH discharges endorsed significantly greater
rates of mental health conditions and substance misuse. They also reported more
negative perceptions of mental health care. Because these veterans may also
experience more barriers to accessing mental health services, it is critical to
consider ways to connect these veterans with needed services.
PMID- 28704792
TI - Cigarette smoking and telomere length: A systematic review of 84 studies and meta
analysis.
AB - BACKGROUND: Cigarette smoking is a risk factor for ageing-related disease, but
its association with biological ageing, indicated by telomere length, is unclear.
METHODS: We systematically reviewed evidence evaluating association between
smoking status and telomere length. Searches were performed in MEDLINE (Ovid) and
EMBASE (Ovid) databases, combining variation of keywords "smoking" and
"telomere". Data was extracted for study characteristics and estimates for
association between smoking and telomere length. Quality of studies was assessed
with a risk of bias score, and publication bias was assessed with a funnel plot.
I2 test was used to observe heterogeneity. Meta-analysis was carried out to
compare mean difference in telomere length by smoking status, and a dose-response
approach was carried out for pack-years of smoking and telomere length. A
sensitivity analysis was carried out to examine sources of heterogeneity.
RESULTS: A total of 84 studies were included in the review, and 30 among them
were included in our meta-analysis. Potential bias was addressed in half of
included studies, and there was little evidence of small study bias. Telomere
length was shorter among ever smokers compared to never smokers (summary standard
mean difference [SMD]: -0.11 (95% CI -0.16 to -0.07)). Similarly, shorter
telomere length was found among smokers compared to non-smokers, and among
current smokers compared to never or former smokers. Dose-response meta-analysis
suggested an inverse trend between pack-years of smoking and telomere length.
However, heterogeneity among some analyses was observed. CONCLUSION: Shorter
telomeres among ever smokers compared to those who never smoked may imply
mechanisms linking tobacco smoke exposure to ageing-related disease.
PMID- 28704793
TI - Genome and transcriptome-wide analyses of cellulose synthase gene superfamily in
soybean.
AB - The plant cellulose synthase gene superfamily belongs to the category of type-2
glycosyltransferases, and is involved in cellulose and hemicellulose
biosynthesis. These enzymes are vital for maintaining cell-wall structural
integrity throughout plant life. Here, we identified 78 putative cellulose
synthases (CS) in the soybean genome. Phylogenetic analysis against 40 reference
Arabidopsis CS genes clustered soybean CSs into seven major groups (CESA, CSL A,
B, C, D, E and G), located on 19 chromosomes (except chromosome 18). Soybean CS
expansion occurred in 66 duplication events. Additionally, we identified 95
simple sequence repeat makers related to 44 CSs. We next performed digital
expression analysis using publically available datasets to understand potential
CS functions in soybean. We found that CSs were highly expressed during soybean
seed development, a pattern confirmed with an Affymatrix soybean IVT array and
validated with RNA-seq profiles. Within CS groups, CESAs had higher relative
expression than CSLs. Soybean CS models were designed based on maximum average
RPKM values. Gene co-expression networks were developed to explore which CSs
could work together in soybean. Finally, RT-PCR analysis confirmed the expression
of 15 selected CSs during all four seed developmental stages.
PMID- 28704794
TI - Genetic engineering as a tool for the generation of mouse models to understand
disease phenotypes and gene function.
AB - The usage of mouse models has been vital for biomedical research over the last
decades, yet the generation of these models has been extremely difficult and
labor-intensive. The identification and generation of nucleases able to introduce
site-specific DNA double-strand breaks, particularly the CRIPSR/Cas system, is a
major breakthrough for this field as the endogenous DNA repair machinery can be
hijacked to specifically introduce genome modifications at these sites. This
allows for the time-efficient and cost-efficient generation of mouse models by
delivery of designer nucleases together with donor DNA into fertilized oocytes.
PMID- 28704795
TI - Endocan concentrations in postmortem serum, vitreous humor and urine in victims
of lethal hypothermia.
AB - Endocan is a soluble molecule secreted from vascular endothelial cells of various
organs. Its exact function in humans remains to be elucidated, though it has been
postulated that increased tissue expression or serum levels of this molecule may
be an indicator of endothelial activation and neovascularization. In the realm of
forensic pathology, studies pertaining to endothelial activation following
exposure to cold exclusively focused on thrombomodulin, a transmembrane protein
specific to endothelial cells. In the study herein described, endocan
concentrations were determined in postmortem serum, urine and vitreous humor
samples collected during autopsy in a series of cases that underwent medicolegal
investigations. A total of 76 autopsy cases were selected and three study groups
(hypothermia group, sepsis group and non-hypothermia/non-sepsis group)
prospectively formed during the study period. The obtained results seem to
indicate that exposure to cold and subsequent death is not distinguished by
significant endothelial dysfunction causing enhanced endocan secretion.
PMID- 28704796
TI - Prison mental health in-reach teams, serious mental illness and the Care
Programme Approach in England.
AB - The delivery of prison mental health services in England is examined over the
last 12 years. Resources for services have grown significantly during this period
and improved organisational models for the delivery of services are now in place.
During this period however the challenges of working in the prison environment
have increased. The paper argues that a history of sexual abuse or violence are
common amongst prisoners and the Care Programme Approach (CPA) provides the
vehicle to assess these histories through the use of routine enquiry.
Commissioners of prison mental health services now need to ensure that teams are
delivering cogent trauma-based interventions where relevant and the outcomes are
measured.
PMID- 28704797
TI - Knockout of RAGE ameliorates mainstream cigarette smoke-induced airway
inflammation in mice.
AB - BACKGROUND: The receptor for advanced glycation end products (RAGE), a
multiligand receptor, has been proved to be implicated in inflammatory responses
in chronic obstructive pulmonary disease (COPD). In this study, we investigated
the role of RAGE in cigarette smoke (CS)-induced airway inflammation in COPD.
METHODS: Wild-type (WT) and RAGE gene knockout (KO) mice were exposed to
mainstream CS or room air for 2h twice daily, 6days per week for consecutive
4weeks. Cell counts and proinflammatory cytokines were measured in
bronchoalveolar lavage fluid (BALF). Lung tissues were collected for histological
examination and gene expression profiling by cDNA microarray. RESULTS: CS
exposure induced significant airway inflammation in WT mice evidenced by
histological inflammatory changes in HE stain with increased neutrophils and
proinflammatory cytokines in the BALF, which were all attenuated by RAGE KO. cDNA
microarray indicated a total of 179 upregulated genes and 351 downregulated genes
in mouse lungs. Among these genes, S100 proteins (S100A8 and S100A9), the RAGE
common ligands, were significantly downregulated, which were validated by real
time qPCR. Further analyses by Gene Ontology, KEGG and Disease Ontology suggested
these differentiated expressed genes significantly related to the immune
inflammatory responses in lungs via crosstalking with a complicated network of
signaling pathways. CONCLUSIONS: Knockout of RAGE significantly ameliorates
mainstream CS-induced airway inflammation in mice possibly via downregulating
S100A8/A9 expression and its related immune-inflammatory responses.
PMID- 28704798
TI - Experimental studies on possible regulatory role of nitric oxide on the
differential effects of chronic predictable and unpredictable stress on adaptive
immune responses.
AB - The present study was designed to investigate the effects of chronic predictable
stress (CPS) and chronic unpredictable stress (CUS) on immunological responses in
KLH-sensitized rats and involvement of NOergic signaling pathways mediating such
responses. Male Wistar rats (200-250g) were exposed to either CPS or CUS for
14days and IgG antibody levels and delayed type hypersensitivity (DTH) response
was determined to assess changes in adaptive immunity. To evaluate the role of
nitric oxide during such immunomodulation, biochemical estimation of stable
metabolite of nitric oxide (NOx) and 3-nitrotyrosine (3-NT, a marker of
peroxynitrite formation) were done in both blood and brain. Chronic stress
exposure resulted in suppression of IgG and DTH response and elevated NOx and 3
NT levels, with a difference in magnitude of response in CPS vs CUS. Pretreatment
with aminoguanidine (iNOS inhibitor) caused further reduction of adaptive immune
responses and attenuated the increased NOx and 3-NT levels in CPS or CUS exposed
rats. On the other hand 7-NI (nNOS inhibitor) did not significantly affect these
estimated parameters. The results suggest involvement of iNOS and lesser/no role
of nNOS during modulation of adaptive immunity to stress. Thus, the result showed
that predictability of stressors results in differential degree of modulation of
immune responses and complex NO-mediated signaling mechanisms may be involved
during responses.
PMID- 28704799
TI - MicroRNA-539 inhibits glioma cell proliferation and invasion by targeting DIXDC1.
AB - Dysregulation of microRNAs (miRNAs) has been suggested to contribute to malignant
progression of glioma. Previous studies have demonstrated that miR-539 is
dysregulated in malignant progression of cancers. However, the potential role and
mechanism of miR-539 in the progression of glioma remains unclear. In this study,
we aimed to investigate the expression status and functional significance of miR
539 in glioma. We found that miR-539 expression was significantly decreased in
glioma cell lines and tissues. Overexpression of miR-539 markedly inhibited
glioma cell proliferation and invasion, while miR-539 suppression exhibited the
opposite effect. Bioinformatics analysis and dual-luciferase reporter assays
showed that miR-539 directly targeted the 3'-untranslated region of Disheveled
axin domain containing 1 (DIXDC1). DIXDC1 expression was negatively regualted by
miR-539 overexpression. An inverse correlation between DIXDC1 mRNA expression and
miR-539 expression was found in glioma specimens. Furthermore, knockdown of DIXC1
significantly inhibited proliferation, invasion and Wnt signaling in glioma
cells. Overexpression of DIXDC1 partially reversed the inhibitory effect of miR
539 on glioma cell proliferation and invasion. Overall, these findings
demonstrate that miR-539 inhibits glioma cell proliferation and invasion by
targeting DIXDC1. Our study suggests that the miR-539 may serve as a potential
target for the clinical diagnosis and treatment of glioma.
PMID- 28704800
TI - Inclusion complex between beta-cyclodextrin and hecogenin acetate produces
superior analgesic effect in animal models for orofacial pain.
AB - Hecogenin acetate (HA) is a steroidal sapogenin-acetylated with pharmacological
properties which have already been described in the literature such as, anti
inflammatory, anti-hyperalgesic and antinociceptive, but it has low solubility in
aqueous media. Therefore, in an attempt to overcome this, we set out to create
inclusion complexes between HA and b-cyclodextrin (b-CD) and evaluate the
antinociceptive effects in the orofacial nociception in mice. The complexes were
prepared using different methods in the molar ratios 1:1 and 1:2 and
characterized physicochemically. The results of the physicochemical
characterization elucidated inclusion complexes formation between b-CD and HA by
freeze drying method in the molar ratio 1:2, which obtained a complexation
efficiency of 92% and produced superior analgesic effect in animal models for
orofacial pain at a lower dose when compared to HA alone.
PMID- 28704801
TI - Stress, depressive status and telomere length: Does social interaction and coping
strategy play a mediating role?
AB - BACKGROUND: Telomeres have been reported to be shorter in individuals exposed to
psychosocial stress and in those with depression. Since negative environmental
stress is a risk factor for depression, the present study tested whether
stressors in childhood (CA) and recent adulthood (NLE) predicted telomere
attrition directly and/or indirectly through individuals' depressive status 3-6
years before TL measurement; and then if social interaction and coping strategies
in adulthood influenced the relationship between depressive status and TL.
METHODS: Participants were 337 individuals with a recent depression diagnosis and
574 screened controls that derived from a longitudinal population-based cohort
study conducted in Stockholm, Sweden. Relative TL was determined using qPCR.
Relationships between the key variables stressors, depressive status, social
interaction, coping strategies and TL were explored by path analysis in males and
females, adjusting for age. RESULTS: The key variables were correlated in
expected directions. In females, depressive status and age had direct negative
effects on TL (p < 0.05) and both CA (p = 0.025) and NLE (p < 0.003) had indirect
negative effects on TL. For males, the effects of stressors and depressive status
on TL were mediated by social interaction (p = 0.005) and the coping strategy
worry (p = 0.005). In females, no mediation effect of social interaction and
coping strategy was detected. LIMITATIONS: Only little of the TL variation was
explained by the models. The environmental stress information was limited.
CONCLUSION: Our findings propose gender-specific paths from environmental
stressors through depressive status, social interaction and coping strategy to
TL.
PMID- 28704802
TI - Trajectories of depressive symptoms and their relationship to the progression of
dementia.
AB - BACKGROUND: The relationship between progression of Alzheimer's disease and
depression and its underlying mechanisms has scarcely been studied. METHODS: A
sample of 282 outpatients with Alzheimer's disease (AD; 105 with amnestic AD and
177 with Alzheimer's dementia) from Norway were followed up for an average of two
years. Assessment included Cornell Scale for Depression in Dementia and Clinical
Dementia Rating Scale (CDR) at baseline and follow-up to examine the relationship
between AD and depression. Additionally, MRI of the brain, CSF dementia
biomarkers and APOE status were assessed at baseline. Progression of dementia was
defined as the difference between CDR sum of boxes at follow-up and baseline (CDR
SB change). Trajectories of depressive symptoms on the Cornell Scale were
identified using growth mixture modeling. Differences between the trajectories in
regard to patients' characteristics were investigated. RESULTS: Three distinct
trajectories of depressive symptoms were identified: 231 (82.8%) of the patients
had stable low-average scores on the Cornell Scale (Class 1); 11 (3.9%) had high
and decreasing scores (Class 2); and 37 (13.3%) had moderate and increasing
scores (Class 3). All classes had average probabilities over 80%, and confidence
intervals were non-overlapping. The only significant characteristic associated
with membership in class 3 was CDR-SB change. LIMITATIONS: Not all patients
screened for participation were included in the study, but the included and non
included patients did not differ significantly. Some patients with amnestic MCI
might have been misdiagnosed. CONCLUSION: A more rapid progression of dementia
was found in a group of patients with increasing depressive symptoms.
PMID- 28704803
TI - Occurrence and fate of organophosphate ester flame retardants and plasticizers in
indoor air and dust of Nepal: Implication for human exposure.
AB - The present study was carried out in Nepal, a landlocked country located between
world's two most populous countries i.e. India and China. In this study, the
occurrence, profiles, spatial distributions and fate of eight organophosphate
ester flame retardants (OPFRs) were investigated in indoor air and house dust.
Overall, the concentrations of ?OPFR were in the range of 153-12100 ng/g
(median732 ng/g) and 0.32-64 ng/m3 (median 5.2 ng/m3) in house dust and indoor
air, respectively. The sources of high OPFR in the indoor environment could be
from locally used wide variety of consumer products and building materials in
Nepalese houses. Significantly, high concentration of tri-cresyl phosphate (TMPP)
was found both in air and dust, while tri (2-ethylhexyl) phosphate (TEHP) had the
highest concentration in air samples. It might be due to fact that the high
concentrations of TMPP are related to intense traffic and/or nearby airports. On
the other hand, significantly high concentration of TEHP could be due to
anthropogenic activities. Only TEHP showed positive correlation between indoor
air and house dust (Rho = 0.517, p < 0.01), while rest of compounds were either
less correlated or not correlated at all. The estimated human exposure to ?OPFR
via different pathway of intake suggested dermal absorption via indoor dust as
major pathway of human exposure to both children and adult population. However,
other pathways of OPFR intake such as dietary or dermal absorption via soil may
still be significant in case of Nepal.
PMID- 28704804
TI - Influence of spectral resolution, spectral range and signal-to-noise ratio of
Fourier transform infra-red spectra on identification of high explosive
substances.
AB - In the contemporary spectroscopy there is a trend to record spectra with the
highest possible spectral resolution. This is clearly justified if the spectral
features in the spectrum are very narrow (for example infra-red spectra of gas
samples). However there is a plethora of samples (in the liquid and especially in
the solid form) where there is a natural spectral peak broadening due to
collisions and proximity predominately. Additionally there is a number of
portable devices (spectrometers) with inherently restricted spectral resolution,
spectral range or both, which are extremely useful in some field applications
(archaeology, agriculture, food industry, cultural heritage, forensic science).
In this paper the investigation of the influence of spectral resolution, spectral
range and signal-to-noise ratio on the identification of high explosive
substances by applying multivariate statistical methods on the Fourier transform
infra-red spectral data sets is studied. All mathematical procedures on spectral
data for dimension reduction, clustering and validation were implemented within R
open source environment.
PMID- 28704805
TI - Biothiols induced colour change of silver nanoparticles: A colorimetric sensing
strategy.
AB - A sensor for the detection and determination of bio-thiols (glutathione (GSH) and
cysteamine (Cyste)) has been developed by integrating the distinguished distance
related optical characteristics of silver nanoparticles with the simplicity of
colorimetric technique. In presence of these analytes, shift in surface plasmon
resonance (SPR) absorption of silver nanoparticles (AgNPs) with change in its
colour was observed. Yellow coloured AgNPs solution becomes colourless in
presence of GSH and changes to red in presence of Cyste. FTIR, TEM and DLS
studies were used to confirm the mechanism. The difference in absorption of AgNPs
in the absence and presence of GSH was found to vary linearly in the range
1.00*10-5M to 5.00*10-7M concentration range with limit of detection at 3.68*10
7M. The method can also be applied to quantify Cyste in the range 1.10*10-6M to
5.00*10-8M with limit of detection at 1.80*10-8M. The utility of the proposed
colorimetric assay is validated by determination of GSH and Cyste in artificial
blood serum.
PMID- 28704806
TI - A molecular rotor based ratiometric sensor for basic amino acids.
AB - The inevitable importance of basic amino acids, arginine and lysine, in human
health and metabolism demands construction of efficient sensor systems for them.
However, there are only limited reports on the 'ratiometric' detection of basic
amino acids which is further restricted by the use of chemically complex sensor
molecules, which impedes their prospect for practical applications. Herein, we
report a ratiometric sensor system build on simple mechanism of disassociation of
novel emissive Thioflavin-T H-aggregates from heparin surface, when subjected to
interaction with basic amino acids. The strong and selective electrostatic and
hydrogen bonding interaction of basic amino acids with heparin leads to large
alteration in photophysical attributes of heparin bound Thioflavin-T, which forms
a highly sensitive sensor platform for detection of basic amino acids in aqueous
solution. These selective interactions between basic amino acids and heparin
allow our sensor system to discriminate arginine and lysine from other amino
acids. This unique mechanism of dissociation of Thioflavin-T aggregates from
heparin surface provides ratiometric response on both fluorimetric and
colorimetric outputs for detection of arginine and lysine, and thus it holds a
significant advantage over other developed sensor systems which are restricted to
single wavelength detection. Apart from the sensitivity and selectivity, our
system also provides the advantage of simplicity, dual mode of sensing, and more
importantly, it employs an inexpensive commercially available probe molecule,
which is a significant advantage over other developed sensor systems that uses
tedious synthesis protocol for the employed probe in the detection scheme, an
impediment for practical applications. Additionally, our sensor system also shows
response in complex biological media of serum samples.
PMID- 28704807
TI - High-Sensitivity Troponin T and NT-proBNP Kinetics in Breast Cancer Chemotherapy.
AB - BACKGROUND/AIMS: Doxorubicin (DOX) and trastuzumab (TRA) are associated with
cardiac dysfunction. METHOD: High-sensitivity troponin T (hs-TnT) and brain
natriuretic peptide attached to the amino acid N-terminal fragment in the
prohormone (NT-proBNP) were measured before and on days +1, +2, +3, and +7 during
cycles 1 and 2 of therapy with DOX or TRA in breast cancer patients. RESULTS:
Five of eleven DOX-treated women, compared with 2/11 TRA-treated women, had
undetectable baseline hs-TnT. By day +1 of cycle 2, all the DOX-treated women (p
= 0.03) but only 7/11 TRA-treated women (p = ns) had detectible hs-TnT. Time to
peak was 1-2 days for both groups. In the DOX-treated women, hs-TnT showed
significant peaks from precycle baseline, increases in precycle 1 to precycle 2
levels, and a cycle 1 to cycle 2 peak and area under the curve (AUC). hs-TnT
increased from precycle (1, 4.6 +/- 6.3 pg/mL) to a cycle 2 peak of 16.1 +/- 15.0
pg/mL (p < 0.002). No increases were seen with the TRA treatment. Transient
posttreatment increases in NT-proBNP were seen after both therapies. CONCLUSION:
DOX was associated with increased pretreatment baseline, peak, and AUC hs-TnT
levels. Both DOX and TRA acutely perturb NT-proBNP. Assessment of pre- and
posttreatment hs-TnT could be a means of quantifying cumulative myocardial injury
in the course of chemotherapy.
PMID- 28704808
TI - Enhanced Reactive Oxygen Species Production, Acidic Cytosolic pH and Upregulated
Na+/H+ Exchanger (NHE) in Dicer Deficient CD4+ T Cells.
AB - BACKGROUND: MicroRNAs (miRNAs) negatively regulate gene expression at a post
transcriptional level. Dicer, a cytoplasmic RNase III enzyme, is required for the
maturation of miRNAs from precursor miRNAs. Dicer, therefore, is a critical
enzyme involved in the biogenesis and processing of miRNAs. Several biological
processes are controlled by miRNAs, including the regulation of T cell
development and function. T cells generate reactive oxygen species (ROS) with
parallel H+ extrusion accomplished by the Na+/H+-exchanger 1 (NHE1). The present
study explored whether ROS production, as well as NHE1 expression and function
are sensitive to the lack of Dicer (miRNAs deficient) and could be modified by
individual miRNAs. METHODS: CD4+ T cells were isolated from CD4 specific Dicer
deficient (DicerDelta/Delta) mice and the respective control mice (Dicerfl/fl).
Transcript and protein levels were quantified with RT-PCR and Western blotting,
respectively. For determination of intracellular pH (pHi) cells were incubated
with the pH sensitive dye bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein
(BCECF) and Na+/H+ exchanger (NHE) activity was calculated from re-alkalinization
after an ammonium pulse. Changes in cell volume were measured using the forward
scatter in flow cytometry, and ROS production utilizing 2',7' -dichlorofluorescin
diacetate (DCFDA) fluorescence. Transfection of miRNA-control and mimics in T
cells was performed using DharmaFECT3 reagent. RESULTS: ROS production, cytosolic
H+ concentration, NHE1 transcript and protein levels, NHE activity, and cell
volume were all significantly higher in CD4+ T cells from DicerDelta/Delta mice
than in CD4+ T cells from Dicerfl/fl mice. Furthermore, individual miR-200b and
miR-15b modify pHi and NHE activity in Dicerfl/fl and DicerDelta/Delta CD4+ T
cells, respectively. CONCLUSIONS: Lack of Dicer leads to oxidative stress,
cytosolic acidification, upregulated NHE1 expression and activity as well as
swelling of CD4+ T cells, functions all reversed by miR-15b or miR-200b.
PMID- 28704809
TI - Istaroxime Inhibits Motility and Down-Regulates Orai1 Expression, SOCE and FAK
Phosphorylation in Prostate Cancer Cells.
AB - BACKGROUND/AIMS: Istaroxime is a validated inotropic Na+/K+ ATPase inhibitor
currently in development for the treatment of various cardiac conditions. Recent
findings established that this steroidal drug exhibits potent apoptotic responses
in prostate tumors in vitro and in vivo, by affecting key signaling orchestrating
proliferation and apoptosis, such as c-Myc and caspase 3, Rho GTPases and actin
cytoskeleton dynamics. In the present study we examined whether istaroxime is
affecting cell motility and analyzed the underlying mechanism in prostate tumor
cells. METHODS: Migration was assessed by transwell and wound healing assays,
Orai1 and Stim1 abundance by RT-PCR and confocal immunofluorescence microscopy,
Fura-2 fluorescence was utilized to determine intracellular Ca2+ and Western
blotting for FAK/pFAK measurements. RESULTS: We observed strong inhibition of
cell migration in istaroxime treated DU-145 prostate cancer cells. Istaroxime
further decreased Orai1 and Stim1 transcript levels and downregulated Orai1
protein expression. Moreover, SOCE was significantly decreased upon istaroxime
treatment. Furthermore, istaroxime strikingly diminished phosphorylated FAK
levels. Interestingly, the efficacy of istaroxime on the inhibition of DU-145
cell migration was further enhanced by blocking Orai1 with 2-APB and FAK with the
specific inhibitor PF-00562271. These results provide strong evidence that
istaroxime prevents cell migration and motility of DU-145 prostate tumor cells,
an effect at least partially attributed to Orai1 downregulation and FAK de
activation. CONCLUSION: Collectively our results indicate that this enzyme
inhibitor, besides its pro-apoptotic action, affects motility of cancer cells,
supporting its potential role as a strong candidate for further clinical cancer
drug development.
PMID- 28704810
TI - Long-Term Prognosis of Alopecia Totalis and Alopecia Universalis: A Longitudinal
Study with More than 10 Years of Follow-Up: Better than Reported.
AB - BACKGROUND: In alopecia totalis (AT) and alopecia universalis (AU), the chance of
full hair regrowth is known to be less than 10%. However, this information is
based on a few older studies conducted in the 1950s and 1960s. OBJECTIVE: We
investigated the current long-term prognosis of individuals with AT/AU. METHODS:
A retrospective chart review was performed in patients with AT/AU between 1994
and 2005. Outcome data were collected by reviewing outpatient clinical files or
by phone interviews. Finally, the long-term assessment of 70 patients with valid
outcome data was performed. RESULTS: Twelve out of 70 patients with AT/AU (17.1%)
had complete hair regrowth. Five out of 24 patients with AT (20.8%) showed
complete hair regrowth, and 7 of 46 patients with AU (15.2%) achieved complete
regrowth. Seventeen out of 70 patients with AT/AU (24.2%) reported hair regrowth
greater than or equal to 90%. Thirty patients with AU (65.2%) remained in an
alopecic state without improvement, while 5 patients with AT (20.8%) showed no
hair regrowth. CONCLUSION: Our results suggest that the long-term prognosis of
AT/AU is more favorable than previously thought. However, the clinical burden of
AT/AU is still substantial.
PMID- 28704811
TI - The Evolution of Cerebrospinal Fluid Shunts: Advances in Technology and
Technique.
AB - Over the past few centuries, there have been many advances in shunt technology,
from the evolution of shunt tubing materials, to advances in valves for
regulating the flow of cerebrospinal fluid (CSF). Additional medical advances
have enabled the antibiotic impregnation of catheters. Finally, advances in
technology have expanded the options for minimally invasive techniques and
improved the management of complicated cases of hydrocephalus. The evolution of
technology and technique in the management of hydrocephalus with CSF shunts will
be discussed here.
PMID- 28704812
TI - SGLT1 Deficiency Turns Listeria Infection into a Lethal Disease in Mice.
AB - BACKGROUND: Cellular glucose uptake may involve either non-concentrative glucose
carriers of the GLUT family or Na+-coupled glucose-carrier SGLT1, which
accumulates glucose against glucose gradients and may thus accomplish cellular
glucose uptake even at dramatically decreased extracellular glucose
concentrations. SGLT1 is not only expressed in epithelia but as well in tumour
cells and immune cells. Immune cell functions strongly depend on their
metabolism, therefore we hypothesized that deficiency of SGLT1 modulates the
defence against bacterial infection. To test this hypothesis, we infected wild
type mice and gene targeted mice lacking functional SGLT1 with Listeria
monocytogenes. METHODS: SGLT1 deficient mice and wild type littermates were
infected with 1x104 CFU Listeria monocytogenes intravenously. Bacterial titers
were determined by colony forming assay, SGLT1, TNF-alpha, IL-6 and IL-12a
transcript levels were determined by qRT-PCR, as well as SGLT1 protein abundance
and localization by immunohistochemistry. RESULTS: Genetic knockout of SGLT1
(Slc5a1-/- mice) significantly compromised bacterial clearance following Listeria
monocytogenes infection with significantly enhanced bacterial load in liver,
spleen, kidney and lung, and significantly augmented hepatic expression of TNF
alpha and IL-12a. While all wild type mice survived, all SGLT1 deficient mice
died from the infection. CONCLUSIONS: SGLT1 is required for bacterial clearance
and host survival following murine Listeria infection.
PMID- 28704813
TI - Serum Ferritin Variations and Mortality in Incident Hemodialysis Patients.
AB - BACKGROUND: Higher serum ferritin levels may be influenced by iron use and
inflammation, and are associated with higher mortality in hemodialysis (HD)
patients. We hypothesized that a major rise in serum ferritin is associated with
a higher risk of mortality, irrespective of baseline serum ferritin in incident
HD patients. METHODS: In a cohort of 93,979 incident HD patients between 2007 and
2011, we examined the association of change in serum ferritin from the baseline
patient quarter (first 91 days from dialysis start) to the subsequent quarter
with mortality. Multivariable adjustments were done for case-mix and markers of
the malnutrition, and inflammation complex and intravenous iron dose. Change in
serum ferritin was stratified into 5 groups: <-400, -400 to <-100, -100 to <100,
100 to <400, and >=400 ng/mL/quarter. RESULTS: The median change in serum
ferritin was 89 ng/mL/quarter (interquartile range -55 to 266 ng/mL/quarter).
Compared to stable serum ferritin (-100 to <100 ng/mL/quarter), a major rise
(>=400 ng/mL/quarter) was associated with higher all-cause mortality (hazard
ratio [95% CI] 1.07 [0.99-1.15], 1.17 [1.09-1.24], 1.26 [1.12-1.41], and 1.49
[1.27-1.76] according to baseline serum ferritin: <200, 200 to <500, 500 to <800,
and >=800 ng/mL in adjusted models, respectively. The mortality risk associated
with a rise in serum ferritin was robust, irrespective of intravenous iron use.
CONCLUSIONS: During the first 6-months after HD initiation, a major rise in serum
ferritin in those with a baseline ferritin >=200 ng/mL and even a slight rise in
serum ferritin in those with a baseline ferritin >=800 ng/mL are associated with
higher mortality.
PMID- 28704814
TI - Acalculous Cholecystitis: Is an Elective Interval Cholecystectomy Necessary.
AB - BACKGROUND: Acute acalculous cholecystitis (AAC) accounts for 5-10% of cases of
acute cholecystitis. The advantage of interval cholecystectomy for patients with
AAC is unclear. Therefore, a retrospective analysis of patients diagnosed with
AAC at our institution was performed over a 5-year period. METHODS: Patients were
identified via hospital coding using the keywords "acalculous cholecystitis,
cholecystostomy and gall bladder perforation." Follow-up data was obtained by
performing a retrospective review of the patients' hospital records. RESULTS: A
total of 33 patients with AAC were identified and followed for a median period of
18 months. The median age at presentation was 70 (10-96) and American Society of
Anesthesiologists (ASA) grade was 3 (1-5). Twenty-three patients (70%) were
treated with antibiotics alone, 7 patients (21%) with percutaneous
cholecystostomy and 3 patients (9%) with laparoscopic cholecystectomy. The 90-day
mortality rate was 30% with significant correlation to comorbid status, as all
deaths occurred in ASA grade 3-5 individuals (p = 0.020). Two patients (6%)
developed recurrent AAC and were managed non-operatively. CONCLUSION: Antibiotics
and cholecystostomy were the mainstay of AAC management, and comorbid status
influenced related mortality. Our results suggest that it appears safe to avoid
interval cholecystectomy in patients who recover from AAC, as they are typically
high-risk surgical candidates.
PMID- 28704815
TI - Relaxation Rate of the Respiratory Muscles and Prediction of Extubation Outcome
in Prematurely Born Infants.
AB - BACKGROUND: Accurate prediction of extubation outcome could result in a
significant reduction of respiratory morbidity in premature neonates. OBJECTIVES:
To assess whether the respiratory muscle time constant of relaxation (tau)
predicted extubation outcome in mechanically ventilated, premature infants.
METHODS: Forty-six mechanically ventilated infants with a median gestational age
of 26 (interquartile range [IQR] 25-29) weeks were prospectively studied. tau was
calculated from the reciprocal of the slope of the decline in airway pressure as
a function of time. Measurements of tau were done during 5-10 min of a
spontaneous breathing test (SBT) prior to extubation. During the first and last
minute of the SBT, tau1 and tau2, respectively, were assessed, and the difference
between them was calculated (Deltatau). RESULTS: The median tau2 was
significantly higher in infants whose extubation failed (20.7 [IQR 12.9-34.7]
s/cm H2O) than in infants whose extubation succeeded (8.2 [IQR 6.2-17.8] s/cm
H2O, p = 0.002). The median Deltatau was significantly higher in infants whose
extubation failed (10.3 [IQR 4.4-23.9] s/cm H2O) than in infants whose extubation
succeeded (-1.63 [IQR -5.7 to 0.3] s/cm H2O, p = 0.001). Extubation failure was
associated with tau2 (p = 0.011) and Deltatau (p = 0.010) after correcting for
postmenstrual age, patent ductus arteriosus, and intraventricular haemorrhage.
Receiver operator characteristic curve analysis demonstrated that Deltatau
predicted extubation failure with an area under the curve of 0.937. A Deltatau of
+1.02 s/cm H2O predicted extubation failure with 94% sensitivity and 83%
specificity. CONCLUSIONS: The respiratory muscle time constant of relaxation
during an SBT was significantly greater in infants whose extubation failed and
could be used to predict extubation outcome in prematurely born infants.
PMID- 28704816
TI - Short versus Extended Duration of Trophic Feeding to Reduce Time to Achieve Full
Enteral Feeding in Extremely Preterm Infants: An Observational Study.
AB - BACKGROUND: Trophic feeding compared to no enteral feeding prevents atrophy of
the gastrointestinal tract. However, the practice of extending the duration of
trophic feeding often delays initiation of full enteral feeding in extremely
preterm infants. We hypothesized that a short duration of trophic feeding (3 days
or less) is associated with early initiation of full enteral feeding. METHODS: A
total of 192 extremely preterm infants (23-28 weeks' gestation) born between 2013
and 2015 were included. Infants were divided into 2 groups according to the
duration of trophic feeding (short vs. extended). The primary outcome was time to
achieve full enteral feeding and the safety outcome was necrotizing enterocolitis
(NEC) and/or death. RESULTS: A short duration of trophic feeding was associated
with a reduction in time to achieve full enteral feeding after adjustment for
birth weight, gestational age, race, sex, type of enteral nutrition, and day of
initiation of trophic feeding (mean difference favoring a short duration of
trophic feeding: -4.1 days; 95% CI: -2.3 to -5.8; p < 0.001). A short duration of
trophic feeding was not associated with a higher risk of NEC and/or death after
achieving full enteral feeding (AOR: 0.91; 95% CI: 0.30-2.77; p = 0.87).
CONCLUSIONS: A short duration of trophic feeding is associated with early
initiation of full enteral feeding. A short duration of trophic feeding is not
associated with a higher risk of NEC, but our study was underpowered for this
safety outcome. Randomized trials are needed to test this study hypothesis.
PMID- 28704817
TI - Outcome of Preterm Neonates with a Birth Weight <1,500 g with Severe Hypoxemic
Respiratory Failure Rescued by Inhaled Nitric Oxide Therapy and High-Frequency
Oscillatory Ventilation.
AB - BACKGROUND: Despite being an experimental therapy in preterm neonates, inhaled
nitric oxide (iNO) is used as a rescue therapy when high-frequency oscillatory
ventilation (HFOV) and other conventional therapies fail. OBJECTIVE: We aimed to
determine the outcomes of very-low-birth-weight (VLBW) neonates with hypoxemic
respiratory failure (HRF) who had received iNO after maximal conventional
therapies. METHODS: We retrospectively reviewed preterm neonates (<33 weeks of
gestation with a birth weight <1,500 g) who had all received HFOV and then iNO
from March 1, 2009 to April 1, 2014 at the Royal Alexandra Hospital. We collected
demographic and clinical parameters, doses, duration and response to iNO,
survival to neonatal intensive care unit (NICU) discharge, major complications,
and neurodevelopmental outcome at 18-24 months of corrected age. RESULTS: During
the study period, 1,168 eligible preterm neonates were admitted; 155 (13%) had
HRF treated with HFOV, of whom 47 (30%) received iNO. The baseline
characteristics between the 24 survivors and 23 nonsurvivors were not different.
Survivors had a greater decrease in oxygenation index than nonsurvivors (61 vs.
33%) after 6 h of iNO (p = 0.003). The causes of death were refractory hypoxemia
(8), multi-organ failure (7), treatment withdrawal (6), and others (2). During
the NICU stay, 23 survivors (96%) developed complications. At 18-24 months, 7
(29%) had significant disabilities. CONCLUSIONS: Of the VLBW neonates with severe
HRF rescued by HFOV and iNO, many survived without neurodevelopmental disability
at early childhood, despite multiple short-term complications. Further research
is necessary to understand the clinical course and risk factors of adverse
outcomes and to improve the management care of these critically ill neonates.
PMID- 28704818
TI - Active Surveillance Cultures and Targeted Decolonization Are Associated with
Reduced Methicillin-Susceptible Staphylococcus aureus Infections in VLBW Infants.
AB - BACKGROUND: Methicillin-susceptible Staphylococcus aureus (MSSA) is a major
contributor to infectious episodes of very low birth weight infants (VLBWI),
resulting in significant morbidity and mortality. OBJECTIVE: To examine the
efficacy and safety of surveillance cultures and the decolonization of MSSA
colonized VLBWI. METHODS: VLBWI admitted to our neonatal wards in 2011-2016 were
retrospectively analyzed. Rates of MSSA-attributable infections were compared
before and after the implementation of active surveillance cultures and the
decolonization of MSSA-colonized patients. The mupirocin susceptibility of
isolated MSSA strains was routinely tested. RESULTS: A total of 1,056 VLBWI were
included in the study, 552 in the pre-intervention period and 504 in the post
intervention period. The implementation of surveillance cultures and
decolonization of colonized patients resulted in a 50% reduction of incidence
rates per 1,000 patient-days of MSSA-attributable infections (1.63 [95% CI 1.12
2.31] vs. 0.83 [95% CI 0.47-1.35], p = 0.024). No adverse effects were observed
from application of the decolonization protocol with mupirocin and octenidin. No
mupirocin-resistant MSSA strains were detected during the study period.
CONCLUSION: Implementation of an active surveillance and decolonization protocol
resulted in a reduction of MSSA-attributable infections in VLBWI.
PMID- 28704819
TI - Electrical Cardiometry to Monitor Cardiac Output in Preterm Infants with Patent
Ductus Arteriosus: A Comparison with Echocardiography.
AB - BACKGROUND: Electrical cardiometry (EC) is an impedance-based monitoring that
provides noninvasive cardiac output (CO) assessment. Through comparison to
transthoracic echocardiography (Echo), the accuracy of EC has been verified.
However, left-to-right patent ductus arteriosus (PDA) shunting is a concern
because PDA shunts aortic flow to the pulmonary artery and may interfere with EC
in measuring CO. OBJECTIVE: To determine the agreement between EC and Echo in
preterm infants with a hemodynamically significant PDA (hsPDA). METHODS: We
reviewed our hemodynamic database in which simultaneous CO measurements by Echo
and EC (Aesculon(r)) were recorded. Preterm infants with left-to-right shunting
hsPDA were enrolled. RESULTS: A total of 105 paired measurements in 36 preterm
infants were compared. Infants' median (range) age and weight at measurement were
27+2 weeks (24+0-33+1) and 1,015 g (518-1,880), with mean (95% CI) ductal
diameter 2.11 mm (1.99-2.22) or 2.15 mm/kg (2.00-2.30). Mean COEC and COEcho were
252 +/- 32 and 258 +/- 45 mL/kg/min, respectively, which demonstrated a moderate
correlation and without a significant between-measurement difference. Bland
Altman analysis showed a bias, limits of agreement, and error percentage of -5.3
mL/kg/min, -78.3 to 67.7 mL/kg/min, and 28.6%, respectively. There was a trend of
increased bias and error percentage of infants with high CO >=280 mL/kg/min and
supported with high-frequency ventilator. CONCLUSIONS: EC and Echo have a wide
but clinically acceptable agreement in measuring CO in preterm infants with
hsPDA. However, for infants with high CO or ventilated by high-frequency
ventilation, interpretation of COEC should be approached with caution.
PMID- 28704820
TI - beta-Carotene Concentration and Its Association with Inflammatory Biomarkers in
Spanish Schoolchildren.
AB - AIM: To examine the correlation between inflammatory biomarkers and plasma beta
carotene levels in children. METHODS: A total of 564 Spanish schoolchildren aged
9-12 were observed and studied. Plasma beta-carotene levels were assessed by
HPLC. A beta-carotene level <4.83 ug/dL (0.09 umol/L) was considered deficient.
Plasma tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) were
measured by immunoenzyme assays. Serum high-sensitivity C-reactive protein (hs
CRP) was tested by immunonephelometry. RESULTS: Subjects who were beta-carotene
deficient (23.1% of the studied children) had higher IL-6 levels than subjects
with normal beta-carotene concentrations. The log-IL-6 and log-hs-CRP
concentrations, but not the log-TNF-alpha level, were strongly and inversely
related to the plasma log-beta-carotene level (taking into account log-age,
energy intake, log-triglycerides, gender, log-body mass index, log-beta-carotene
intake, energy from lipids and cholesterol as covariables). When the 3
inflammatory biomarkers were introduced into the regression model along with the
corresponding covariables, only the log-IL-6 level was related to the plasma log
beta-carotene level (beta = -0.505 +/- 0.078; p < 0.001). CONCLUSIONS:
Inflammatory status, in particular IL-6 levels, appears to be negatively
associated with plasma beta-carotene levels in schoolchildren.
PMID- 28704821
TI - Application of the DruGeVar Database in Cancer Genomics and Pharmacogenomics.
AB - In the post-genomic era, there is an increasing and urgent need for managing and
visualizing big data. Data complexity and size will turn information growth into
knowledge growth only if presented in a comprehensive and user-friendly way. In
such a context, the information technology community collaborates in a
multidisciplinary manner with other scientific fields searching for and/or
developing tools and services for data management and visualization. We have
previously developed DruGeVar, a comprehensive database that triangulates drugs
with genes and pharmacogenomic biomarkers to serve clinical pharmacogenomics. To
empower its functionality, we explored and implemented new visualization tools,
such as POWER-BI (Microsoft), which allows for interactive visualization. Herein,
we describe the synergy of POWER-BI and DruGeVar, focusing on cancer genomics
data in light of translational pharmacogenomics.
PMID- 28704822
TI - Prediction of Outcome in Neonates with Hypoxic-Ischemic Encephalopathy II: Role
of Amplitude-Integrated Electroencephalography and Cerebral Oxygen Saturation
Measured by Near-Infrared Spectroscopy.
AB - BACKGROUND: Few data have been published on the combined use of amplitude
integrated electroencephalography (aEEG) and near-infrared spectroscopy (NIRS)
for outcome prediction in neonates cooled for hypoxic-ischemic encephalopathy
(HIE). OBJECTIVE: Our aim was to evaluate the predictive values and the most
powerful predictive combinations of single aEEG and NIRS parameters and the
respective cut-off values with regard to short-term outcomes in HIE II. METHODS:
aEEG and NIRS were prospectively studied at the Medical University of Vienna in
the first 102 h of life with regard to magnetic resonance imaging (MRI). Thirty
two neonates diagnosed with HIE II treated with hypothermia were investigated.
The measurement period was divided into 6-h epochs. According to MRI, 2 outcome
groups were defined and predictive values of aEEG parameters, regional cerebral
oxygen saturation (rScO2), and the additional value of both methods combined were
studied. Receiver operating curves (ROC) were obtained and area under the curve
(AUC) values were calculated. ROC were then used to detect the optimal cut-off
points, sensitivity, specificity, positive predictive values, and negative
predictive values. RESULTS: At all time epochs, combined parameter scores were
more predictive than single parameter scores. The highest AUC were observed
between 18 and 60 h of cooling for the aEEG summation score (0.72-0.84) and for
(background pattern + seizures) * rScO2 (0.79-0.85). At 42-60 h sensitivity was
similar between those 2 scores (87.5-90.0%), but the addition of NIRS to aEEG led
to an increase in specificity (from 52.4-59.1% to 72.7-90.5%). CONCLUSIONS: In
HIE II, aEEG and NIRS are important predictors of short-term outcome. The
combination of both methods improves prognostication. The highest predictive
abilities were observed between 18 and 60 h of cooling.
PMID- 28704823
TI - Different Behavior and Response of Staphylococcus Epidermidis and Streptococcus
Pneumoniae to a Ventriculoperitoneal Shunt: An in vitro Study.
AB - BACKGROUND: Pneumococcal shunt infection is a rare event. There is no consensus
on the therapeutic management of this kind of shunt infection according to
literature reviews, and it seems to be different from infection with
Staphylococcus epidermidis. We studied 2 shunted patients with pneumococcal
meningitis, both of whom were treated with only antibiotics. The management of
these cases seems to be different from that of shunt catheter infection due to
these bacteria. We conducted a laboratory study to show the different behavior of
pneumococcus compared to S. epidermidis regarding shunt catheter colonization.
MATERIALS AND METHODS: S. epidermidis and Streptococcus pneumoniae bacteria
isolated from the cerebrospinal fluid of meningitis patients were incubated in
sterile media. Forty-five segments of shunt catheter from silicone material were
placed in 45 separate media of S. epidermidis and pneumococcus. Then each
catheter was washed and cultured in blood chocolate agar growth medium in
separate petri dishes via the roll plate method. The dishes were extracted from
the incubator and the colony count was calculated after 72 h. RESULTS: The colony
count was obviously different between the 2 bacteria groups, with a higher count
related to S. epidermidis dishes. The colony count of the pneumococcal petri
dishes was 25-35,000 (mean 14,337) and for dishes with S. epidermidis it was
14,000-100,000 (mean 50,125) (p = 0.001). CONCLUSION: The adherence of
pneumococcus to shunt catheters seems to be much less than that of S.
epidermidis, which produced a very low colony count when incubated with the
catheter in the medium culture. S. pneumoniae meningitis in shunted patients can
be managed successfully with only antibiotics. This approach can prevent problems
related to the several additional surgeries required for shunt removal, a new
shunt insertion, and the management of high intracranial pressure.
PMID- 28704824
TI - The Impact of Low-Grade Germinal Matrix-Intraventricular Hemorrhage on
Neurodevelopmental Outcome of Very Preterm Infants.
AB - BACKGROUND: Very preterm infants often show germinal matrix-intraventricular
hemorrhage (GMH-IVH) on cranial ultrasound (cUS). AIM: To determine the impact of
low-grade GMH-IVH on early neurodevelopmental outcome in very preterm infants.
METHODS: A retrospective case-control study in very preterm infants with and
without low-grade GMH-IVH on cUS. Additional magnetic resonance imaging (MRI) was
available in all infants with a gestational age (GA) <28 weeks and high-risk
infants >28 weeks. Infants were seen at 2 years' corrected age to assess
neurodevelopment. RESULTS: In total, 136 infants (GA 24-32 weeks) with low-grade
GMH-IVH on cUS were matched with 255 controls. Outcome data was available for 342
(87%) infants. Adverse outcome (i.e., cerebral palsy [CP], neurodevelopmental
delay) was present in 11 (9%) cases and 20 (9%) controls. No statistically
significant differences in outcome were found between cases and controls.
Additional MRI was performed in 165/391 infants (42%) and showed additional
lesions in 73 (44%) infants that could explain subsequent development of CP in 2
out of 5 infants and epilepsy in 1 of 2 infants. CONCLUSION: Very preterm infants
with low-grade GMH-IVH on cUS have a similar early neurodevelopmental outcome
compared with controls. Additional MRI showed mostly subtle abnormalities that
were missed with cUS, but these could not explain subsequent development of CP
and developmental delay in all infants.
PMID- 28704825
TI - Dexamethasone Implants in Diabetic Macular Edema Patients with High Visual
Acuity.
AB - PURPOSE: To evaluate the effects of intravitreal dexamethasone (DEX) implants in
patients affected by diabetic macular edema (DME) with high best-corrected visual
acuity (BCVA) and contraindications to therapy with anti-vascular endothelial
growth factor over a 12-month follow-up. METHODS: In this interventional
nonrandomized clinical study, 14 consecutive patients (14 eyes) affected by DME
with a BCVA of 0.3 LogMAR or better were prospectively enrolled. All patients
were treated with a sustained-release 700-MUg DEX implant at baseline, revaluated
every 6 weeks, and retreated on a pro re nata basis. Primary outcomes included
changes in BCVA and central macular thickness (CMT). Secondary outcomes included
number of implants, average period between injections, and incidence of side
effects. RESULTS: At the 12-month examination, a significant improvement in mean
BCVA was noted compared to baseline (from 0.25 +/- 0.05 to 0.10 +/- 0.07 LogMAR;
p < 0.001); CMT decreased from 484 +/- 127 to 311 +/- 51 MUm (p < 0.001). No
differences in BCVA and CMT improvements were found between treatment- naive
patients and previously treated patients (p = 0.768 and 0.119, respectively). The
mean number of implants was 1.71 +/- 0.61 (range, 1-3). The mean period between
the first and the second implant was 6.1 +/- 1.6 months. CONCLUSIONS: The DEX
implant on a pro re nata basis can be considered a beneficial approach for DME
patients with high BCVA over a 12-month follow-up; functional and anatomical
outcome of the patients significantly improved with few injections and a good
safety profile.
PMID- 28704826
TI - Dialysis in the Elderly and Impact of Institutionalization in the United States
Renal Data System.
AB - BACKGROUND: We hypothesized that in the very elderly dialysis patients in the
United States, institutionalization in nursing homes would increase mortality in
addition to age alone. METHODS: Incident dialysis patients from 2001 to 2008
above the age of 70 were included. Patients above 70 were categorized into 4
groups according to age as 70-75, 76-80, 81-85, and >85 years and further divided
into institutionalized and noninstitutionalized. Kaplan-Meier survival curves
were plotted to assess patient survival. RESULTS: A total of 349,440 patients
were identified above the age of 70 at the time of initiation of dialysis. For
institutionalized patients, the mean survival was significantly lower, 1.71 +/-
0.03 years for those in the age range 70-75, 1.44 +/- 0.02 years for those in the
age range 76-80, 1.25 +/- 0.02 years for those in the age range 81-85, and 1.04
+/- 0.02 for those in the >85 years age group (p = 0.0001). The hazard ratio for
mortality in institutionalized elderly patients on dialysis was 1.80 ([95% CI
1.77-1.83]; p = 0.0001). After adjustment for other variables (multivariate Cox
regression), to be institutionalized was still an independent risk factor for
mortality (adjusted hazard ratio = 1.57 [95% CI 1.54-1.60]; p = 0.0001).
CONCLUSION: There was increased mortality in institutionalized elderly patients
as compared to noninstutionalized elderly patients in the same age group. In
accordance with the increased frailty and decreased benefits of therapies in the
very elderly, especially in those with additional co-morbidities besides age,
palliative and end-of-life care should be considered.
PMID- 28704827
TI - Age-Dependent Changes in Regulatory T Lymphocyte Development and Function: A Mini
Review.
AB - The generation and function of immuno-suppressive regulatory T lymphocytes
(Treg), which can differentiate in the thymus (tTreg) or in the periphery
(pTreg), are regulated in an age-dependent manner. tTreg are produced at high
levels in the first weeks of age, when they expand and colonize secondary
lymphoid organs and peripheral tissues to protect the organism from autoimmune
diseases and to promote tissue repair. Once this population of Treg is
operational in the periphery, at puberty, thymic output of Treg declines, but
self-reactive tTreg generated early on in life are maintained over time and play
a major role in preserving homeostasis of the immune system. Extra-thymic pTreg
differentiation declines later on in life. pTreg generated throughout life mainly
protect the organism from chronic inflammation and the semi-allogeneic fetus from
rejection. In this review, age-dependent modulation of the production and
function of these two populations of Treg is described.
PMID- 28704828
TI - Extremely High Prevalence of Maternal and Neonatal Vitamin D Deficiency in the
Arab Population.
AB - BACKGROUND: Vitamin D deficiency is a global public health problem. The published
literature on vitamin D deficiency is limited among Arab pregnant women and its
association with different metabolic markers. OBJECTIVE: To determine the
prevalence of vitamin D deficiency in Arab pregnant women and neonates and its
association with various biomarker profiles. METHODS: This is a multicenter study
taken from a large prospective project in Riyadh, the capital city of Saudi
Arabia. Maternal biochemical levels were measured routinely. Maternal and
neonatal 25(OH)D levels were assessed using a chemiluminescence immunoassay. A
total of 1,097 pregnant women >16 years old with gestational ages <24 weeks were
recruited from different tertiary hospitals in Riyadh between February 2011 and
June 2012. RESULTS: Almost 85% of pregnant subjects had 25(OH)D level <50 nmol/L.
Vitamin D deficiency among neonates was 88%. Maternal 25(OH)D was significantly
associated with neonatal 25(OH)D (r = 0.54, p < 0.01), as well as serum calcium
(r = 0.16, p = 0.02) and phosphate levels (r = 0.17, p = 0.02), and had an
inverse correlation with parathyroid hormone (r = -0.22, p = 0.001). CONCLUSION:
Maternal and neonatal vitamin D deficiency is alarmingly high in Arabs and
significantly associated with each another. Universal screening for serum 25(OH)D
may be appropriate for Arab mothers and vitamin D supplementation mandatory until
term. The study puts a spotlight on vitamin D deficiency with the hope that
health professionals will address it adequately to prevent the known long-term
consequences for metabolism and bone health of both mothers and their children.
PMID- 28704829
TI - Prevalence of and Risk Factors for Secondary Traumatization in Interpreters for
Refugees: A Cross-Sectional Study.
AB - BACKGROUND: A substantial proportion of refugees, fleeing persecution, torture,
and war, are estimated to suffer from psychological traumatization. After being
sheltered in reception centers, the refugees come in close contact with different
occupational groups, e.g., physicians, social workers, and interpreters. Previous
studies ascertained that such interpreters themselves often suffer from primary
psychological traumatization. Moreover, through translating refugees' potentially
traumatic depictions, the interpreters are in danger of developing a so-called
secondary traumatization. OBJECTIVE: The present study aimed (1) to analyze the
prevalence rates of primary traumatization in interpreters, (2) to assess the
prevalence of secondary traumatization, depression, anxiety, and stress symptoms,
(3) to examine the association between secondary traumatization symptoms and
resilience factors in terms of sense of coherence, social support, and attachment
style, and (4) to test whether these resilience factors mediate the relationship
between primary and secondary traumatization. METHODS: Participating interpreters
(n = 64) were assessed for past exposure to potentially traumatic events as well
as symptoms of posttraumatic stress disorder (PTSD), secondary traumatization,
depressive symptoms, anxiety, and subjective stress levels. Furthermore, we
conducted psychometric surveys to measure interpreters' sense of coherence,
degree of social support, and attachment style as potential predictors. RESULTS:
(1) 9% of the interpreters fulfilled all criteria for PTSD and a further 33% had
subclinical PTSD; (2) a secondary traumatization was present in 21% of the
examined interpreters - of these, 6% showed very high total scores indicating a
severe secondary traumatization; furthermore, we found higher scores for
depression, anxiety, and stress as compared to representative population samples,
especially for females; (3) a present sense of coherence, an existing social
support network, and a secure or preoccupied attachment style correlated
significantly with low scores for secondary traumatization; and (4) a significant
correlation emerged between primary and secondary traumatization (r = 0.595, p <
0.001); a mediation analysis revealed that this effect is partially mediated by
secure attachment. CONCLUSION: A substantial proportion of interpreters working
with refugees suffer from primary as well as secondary traumatization. However,
high scores for sense of coherence and social support, male gender, and
especially a secure attachment style were identified as resilience factors for
secondary traumatization. The results may have implications for the selection,
training, and supervision of interpreters.
PMID- 28704831
TI - Reticulocyte Haemoglobin Content Declines More Markedly in Preterm than in Term
Infants in the First Days after Birth.
AB - BACKGROUND: Reticulocyte haemoglobin content, i.e., the reticulocyte equivalent
(Ret-He), seems to be a promising parameter for the detection of iron deficiency
(ID) in neonates because it can be obtained as part of a reticulocyte count, with
no additional blood loss and at no extra cost. Due to the short life span of
reticulocytes, Ret-He reflects current iron availability for erythropoiesis more
accurately than other common erythrocyte indices. OBJECTIVE: We aimed to evaluate
postnatal changes in Ret-He within the first days after birth in term and preterm
infants with the hypothesis that preterm infants experience a more pronounced
postnatal reduction in Ret-He when compared to term infants. METHODS: We
conducted retrospective analyses of clinically indicated blood samples. Paired t
test and mixed regression modelling were used. RESULTS: In total, 805 blood
samples obtained from 207 term and 295 preterm infants were analysed. Ret-He
decreased by 1.5 pg per day (regression coefficient [95% CI] -1.5 [-1.8 to -1.2]
pg, p < 0.0001). This drop was more significant in preterm infants (regression
coefficient -2.2 [-2.6 to -1.8] pg, p < 0.0001) than in term infants (regression
coefficient -0.8 [-1.3 to -0.2] pg, p < 0.01, pinteraction < 0.0001). CONCLUSION:
Ret-He declined within the first days after birth. The observed changes with
postnatal age were more pronounced in preterm than in term infants. Further
studies are needed to evaluate if these changes are due to developing ID or other
causes.
PMID- 28704830
TI - Sirtuins in Skin and Skin Cancers.
AB - The sirtuins are a family of proteins that comprise class III of the histone
deacetylases. These NAD+-dependent proteins have been found to be intricately
involved in a variety of important and skin-relevant cellular functions and
processes, including aging, UV damage response, oxidative stress, and wound
repair. In addition, recent research is unraveling the role of sirtuins in a
variety of skin diseases, including melanoma and nonmelanoma skin cancers. In
this review, we provide a discussion on the potential roles and implications of
different sirtuins in skin-specific cellular processes, which may have relevance
to skin health and skin diseases. Based on the available literature, the sirtuins
appear to be important targets in the management of a variety of skin diseases
from cosmetic (e.g., skin aging) to fatal conditions (e.g., melanoma).
PMID- 28704832
TI - Cerebral and Renal Oxygen Saturation Are Not Compromised in the Presence of
Retrograde Blood Flow in either the Ascending or Descending Aorta in Term or Near
Term Infants with Left-Sided Obstructive Lesions.
AB - BACKGROUND: In infants with left-sided obstructive lesions (LSOL), the presence
of retrograde blood flow in either the ascending or descending aorta may lead to
diminished cerebral and renal blood flow, respectively. OBJECTIVES: Our aim was
to compare cerebral and renal tissue oxygen saturation (rSO2) between infants
with LSOL with antegrade and retrograde blood flow in the ascending aorta and
with and without diastolic backflow in the descending aorta. METHODS: Based on 2
echocardiograms, the study group was categorized according to the direction of
blood flow in the ascending and descending aorta. We measured cerebral and renal
rSO2 using near-infrared spectroscopy and calculated fractional tissue oxygen
extraction (FTOE). RESULTS: Nineteen infants with LSOL, admitted to the NICU
between 0 and 28 days after birth, were included. Infants with antegrade blood
flow (n = 12) and infants with retrograde blood flow in the ascending aorta (n =
7) had similar cerebral rSO2 and FTOE during both echocardiograms. Only during
the first echocardiogram, infants with retrograde blood flow in the ascending
aorta had lower renal FTOE (0.14 vs. 0.32, p = 0.04) and tended to have higher
renal rSO2 (80 vs. 65%, p = 0.09). The presence of diastolic backflow in the
descending aorta was not associated with cerebral or renal rSO2 and FTOE during
the first (n = 8) as well as the second echocardiogram (n = 10). CONCLUSIONS:
Retrograde blood flow in the ascending aorta was not associated with cerebral
oxygenation, while diastolic backflow in the descending aorta was not associated
with renal oxygenation in infants with LSOL.
PMID- 28704833
TI - Pica in a Child with Anterior Cingulate Gyrus Oligodendroglioma: Case Report.
AB - The anterior cingulate gyrus (ACG) is a continued focus of research as its exact
role in brain function and vast connections with other anatomical locations is
not fully understood. A review of the literature illustrates the role the ACG
likely plays in cognitive and emotional processing, as well as a modulating role
in motor function and goal-oriented behaviors. While lesions of the cingulate
gyrus are rare, each new case broadens our understanding of its role in cognitive
neuroscience and higher order processing. The authors present the case of an 8
year-old boy with a 1-month history of staring spells, agitated personality, and
hyperphagia notable for the consumption of paper, who was found to have a 3-cm
tumor in the left ACG. Following surgical resection of the tumor, his aggressive
behavior and pica were ameliorated and the patient made an uneventful recovery,
with no evidence of recurrence over the last 6 years since surgical resection.
Here we discuss a unique behavioral presentation of pica, along with a review of
the current literature, to illustrate functions of the ACG relevant to the
location of the lesion.
PMID- 28704834
TI - GPER Mediates Functional Endothelial Aging in Renal Arteries.
AB - Aging is associated with impaired renal artery function, which is partly
characterized by arterial stiffening and a reduced vasodilatory capacity due to
excessive generation of reactive oxygen species by NADPH oxidases (Nox). The
abundance and activity of Nox depends on basal activity of the heptahelical
transmembrane receptor GPER; however, whether GPER contributes to age-dependent
functional changes in renal arteries is unknown. This study investigated the
effect of aging and Nox activity on renal artery tone in wild-type and GPER
deficient (Gper-/-) mice (4 and 24 months old). In wild-type mice, aging markedly
impaired endothelium-dependent, nitric oxide (NO)-mediated relaxations to
acetylcholine, which were largely preserved in renal arteries of aged Gper-/-
mice. The Nox inhibitor gp91ds-tat abolished this difference by greatly enhancing
relaxations in wild-type mice, while having no effect in Gper-/- mice.
Contractions to angiotensin II and phenylephrine in wild-type mice were partly
sensitive to gp91ds-tat but unaffected by aging. Again, deletion of GPER
abolished effects of Nox inhibition on contractile responses. In conclusion,
basal activity of GPER is required for the age-dependent impairment of
endothelium-dependent, NO-mediated relaxation in the renal artery. Restoration of
relaxation by a Nox inhibitor in aged wild-type but not Gper-/- mice strongly
supports a role for Nox-derived reactive oxygen species as the underlying cause.
Pharmacological blockers of GPER signaling may thus be suitable to inhibit
functional endothelial aging of renal arteries by reducing Nox-derived oxidative
stress and, possibly, the associated age-dependent deterioration of kidney
function.
PMID- 28704835
TI - High Prevalence of Pulmonary Hypertension Complicates the Care of Infants with
Omphalocele.
AB - BACKGROUND: Omphalocele is one of the most common abdominal wall defects. Many
newborn infants born with omphalocele present with significant respiratory
distress at birth, requiring mechanical ventilatory support, and have clinical
evidence of pulmonary hypertension. Little information exists on the prevalence
of and risk factors associated with pulmonary hypertension in this cohort of
infants. OBJECTIVES: To describe the prevalence of and risk factors associated
with pulmonary hypertension among infants with omphalocele. METHODS: This is a
multicenter retrospective chart review of demographic data and clinical
characteristics of infants with omphalocele admitted to the neonatal intensive
care units of Loma Linda University Children's Hospital and Children's Mercy
Hospital between 1994 and 2011. Echocardiogram images were reviewed for pulmonary
hypertension, and statistical analyses were performed to identify risk factors
associated with the presence of pulmonary hypertension. RESULTS: Pulmonary
hypertension was diagnosed in 32/56 (57%) infants with omphalocele. Compared to
infants without pulmonary hypertension, infants with pulmonary hypertension were
more likely to have a liver-containing defect (16/32 [50%] vs. 5/24 [21%], p =
0.03), require intubation at birth (18/32 [56%] vs. 6/24 [17%], p = 0.03), and
die during initial hospitalization (12/32 [38%] vs. 2/24 [8%], p = 0.01).
CONCLUSION: The majority of infants with omphalocele have evidence of pulmonary
hypertension which is associated with increased mortality. Echocardiograms to
screen for pulmonary hypertension should be obtained at >=2 days of life in
infants with omphalocele, especially in those with liver within the omphalocele
sac and/or in those infants who require intubation at birth to screen for
pulmonary hypertension.
PMID- 28704836
TI - Abdominal Near-Infrared Spectroscopy Detects Low Mesenteric Perfusion Early in
Preterm Infants with Hemodynamic Significant Ductus Arteriosus.
AB - BACKGROUND: The therapeutic decision to close patent ductus arteriosus in preterm
infants entails great uncertainty. Near-infrared spectroscopy is a noninvasive
bedside technique used to monitor mixed regional oxygen saturation. We
hypothesized that near-infrared spectroscopy could identify preterm infants at
risk of mesenteric hypoperfusion associated with hemodynamically significant
ductus arteriosus. METHODS: This is a prospective observational study including
consecutively admitted preterm infants with a gestational age <32 weeks.
Mesenteric regional oxygenation was blindly monitored using an INVOS 5100 device.
The presence of a hemodynamically significant patent ductus arteriosus was
routinely confirmed by echocardiography/Doppler. Statistical analysis including
Bland-Altman plots was performed to assess near-infrared spectroscopy
intraobserver repeatability. RESULTS: A total of 72 preterm infants were
enrolled. The daily mean regional oxygen saturation for preterm infants was
determined both in mesenteric and cerebral regions and plotted against time. We
identified a differential temporary baseline. Hemodynamic significant ductus
arteriosus was associated with lower blood pressures and lower regional
splanchnic oxygenation. There was a significant relationship between reversal
diastolic flow in the descending aorta and the regional oxygen saturation, which
remained significant after controlling for ductal size and nil per os.
CONCLUSIONS: The simultaneous monitoring of splanchnic near-infrared spectroscopy
and echocardiography could identify low mesenteric perfusion in the presence of
hemodynamic ductus arteriosus.
PMID- 28704837
TI - Hamburg-Glasgow classification: preoperative staging by combination of
disseminated tumour load and systemic inflammation in oesophageal carcinoma.
AB - BACKGROUND: The aim of this study was to establish a new preoperative staging
classification and evaluate its comparability to the post-operative tumour stage,
lymph node invasion and metastasis (TNM) classification. To date, adequate,
preoperative staging in patients with oesophageal carcinoma (EC) is still missing
but urgently needed. Systemic inflammation and disseminated tumour load have a
pivotal role in recurrence and oncological outcome. To improve the clinical
staging, we merged the Glasgow Prognostic Score (GPS) and disseminated tumour
cells (DTC) into a new sufficient preoperative staging classification, the
Hamburg-Glasgow classification (HGC). METHODS: In this prospective, single-centre
study, 326 patients following curative oesophagectomy were included. From all
patients preoperative bone marrow was aspirated from the iliac crest to detect
DTCs by immunostaining with the pan-keratin antibody A45-B/B3. HGC was subdefined
into four prognostic groups on the basis of C-reactive protein (CRP), albumin and
DTC. The three prognostic groups of the GPS were supplemented by DTC detection
status. Results were correlated with clinicopathological parameters and clinical
outcome. RESULTS: Increasing HGC significantly correlated with lymph node
invasion (P=0.022), post-operative pathohistological TNM staging (P=0.001) and
tumour recurrence (P=0.001). The four HGC prognostic groups displayed a gradual
decrease in overall as well as disease-free survival (P<0.001, each). Hamburg
Glasgow classification was a strong, significant independent predictor of overall
survival and disease-free survival (P<0.001, both) in multivariate analysis.
CONCLUSIONS: Hamburg-Glasgow classification seems to be a promising preoperative
additive staging classification for accurate and simple outcome stratification.
PMID- 28704838
TI - Inhibition of OATP1B1 by tyrosine kinase inhibitors: in vitro-in vivo
correlations.
AB - This corrects the article DOI: 10.1038/bjc.2013.811.
PMID- 28704839
TI - The role of miRNAs in human papilloma virus (HPV)-associated cancers: bridging
between HPV-related head and neck cancer and cervical cancer.
AB - This corrects the article DOI: 10.1038/bjc.2012.109.
PMID- 28704840
TI - HYPE or HOPE: the prognostic value of infiltrating immune cells in cancer.
AB - Interactions between immune and malignant cells have been known to have clinical
relevance for decades. The potential for immune control is now being
therapeutically enhanced with checkpoint inhibitors and other novel agents to
improve outcomes in cancer. The importance of the immune infiltrate as a
prognostic marker is increasingly relevant. In this minireview, we present an
overview of the immune infiltrate and its spatial organisation, and summarise the
prognostic value of immune cells in different cancer types. International
collaborative efforts are standardising histopathologic reporting of the immune
infiltrate, to allow application of these parameters in the clinical and research
settings. In general terms, a 'pro-inflammatory' tumour microenvironment and
infiltrating CD8-expressing T lymphocytes are associated with improved clinical
outcomes in a broad range of tumour types. The inhibitory function of other
immune cells, for example, myeloid-derived suppressor cells and regulatory T
cells, appear to have a major role in disrupting the capacity for the immune
control of cancers.
PMID- 28704841
TI - Lifestyle predictors for non-participation and outcome in the second round of
faecal immunochemical test in colorectal cancer screening.
AB - BACKGROUND: To reduce colorectal cancer (CRC) mortality through population-based
screening programmes using faecal tests, it is important that individuals
continue to participate in the repeated rounds of screening. We aimed to identify
lifestyle predictors for discontinuation of faecal immunochemical test (FIT)
screening after the first round, as well as lifestyle predictors for colorectal
neoplasia detected in the second-round FIT screening. METHODS: In this
longitudinal study, we invited 6959 individuals aged 50-74 years from south-east
Norway for a first round of FIT screening and to complete a self-reported
lifestyle questionnaire on demographic factors, body mass index (BMI, kg m-2),
smoking habits, physical activity, consumption of alcohol and dietary items. Two
years later, we estimated the associations between these factors, non
participation and screening results in the second round of FIT screening using
adjusted odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Of the
3114 responders to the questionnaire who completed the first-round FIT and who
were invited to participate in second-round FIT screening, 540 (17%) did not
participate. The OR and (95% CI) for discontinuation of FIT screening after the
first round was 1.61 (1.24-2.10) for current smoking compared with non-smoking;
2.01 (1.25-3.24) for BMI?35 kg m-2 compared with BMI 16.9-24.9 kg m-2 and 0.70
(0.52-0.94) for physical activity in the third quartile vs the first. Among
participants, smoking, high BMI and high alcohol consumption were associated with
an increased odds of detecting colorectal neoplasia (n=107). CONCLUSIONS: These
results may indicate that Norwegian FIT screening participants who discontinue
after the first round have lifestyle behaviours associated with increased risk of
CRC.
PMID- 28704842
TI - Analysis of metabolomic profile of fermented Orostachys japonicus A. Berger by
capillary electrophoresis time of flight mass spectrometry.
AB - Microbial cell performance in food biotechnological processes has become an
important concern for improving human health worldwide. Lactobacillus plantarum,
which is widely distributed in nature, is a lactic acid bacterium with many
industrial applications for fermented foods or functional foods (e.g.,
probiotics). In the present study, using capillary electrophoresis time of flight
mass spectrometry, the metabolomic profile of dried Orostachys japonicus A.
Berger, a perennial medicinal herb with L. plantarum was compared with that of O.
japonicus fermented with L. plantarum to elucidate the metabolomic changes
induced by the fermentation process. The levels of several metabolites were
changed by the fermentation process, indicating their involvement in microbial
performance. For example, glycolysis, the pentose phosphate pathway, the TCA
cycle, the urea cycle-related metabolism, nucleotide metabolism, and lipid and
amino acid metabolism were altered significantly by the fermentation process.
Although the fermented metabolites were not tested using in vivo studies to
increase human health benefits, our findings provide an insight into the
alteration of metabolites induced by fermentation, and indicated that the
metabolomic analysis for the process should be accompanied by fermenting strains
and conditions.
PMID- 28704843
TI - Outcomes of Infants Who Failed to Extubate despite Systemic Corticosteroids.
PMID- 28704844
TI - Risk Factors for Postpartum Septic Pelvic Thrombophlebitis: A Multicenter Cohort.
PMID- 28704845
TI - Changes in Neonatal Mineral Administration and Contaminant Exposure due to Sodium
Phosphate Shortage.
PMID- 28704846
TI - The Effect of Treated Overt Hypothyroidism on Outcomes in Twin Pregnancies.
PMID- 28704847
TI - Prophylactic Wound Vacuum Therapy after Cesarean Section to Prevent Wound
Complications in the Obese Population: A Randomized Controlled Trial (the ProVac
Study).
PMID- 28704848
TI - Red Cell Distribution Width as a Predictor of Persistent Pulmonary Hypertension
of the Newborn.
PMID- 28704849
TI - Prevention of Preterm Labor with 17alpha-Hydroxyprogesterone (17OHP) Caproate: A
Comparison of Adverse Drug Reaction Rates between Compounded and Commercial
Formulations.
PMID- 28704850
TI - High-Normal Glucose Levels in a Routine Oral 1-Hour 50 g Glucose Challenge Test
Are Associated with a Poorer Glycemic Status Later in Life.
PMID- 28704851
TI - Melatonin and Neonatal Sepsis: A Promising Antioxidant Adjuvant Agent.
PMID- 28704852
TI - Pregnancy and Tumor Outcomes in Women with Prolactinoma.
AB - Context Management of prolactinomas during pregnancy has always been a challenge.
There is a concern about the risk of tumor growth, as well as the effects of the
treatment on the developing fetus. Another issue that has been less studied is
the outcome of women with prolactinoma after pregnancy and lactation. Objectives
To evaluate remission of hyperprolactinaemia after pregnancy and lactation in
women with prolactinoma. To describe the safety of dopamine agonists for the
fetus and pregnancy outcomes. Methods A retrospective study of 32 pregnancies in
women with prolactinoma was conducted in a single-centre. Other causes of
hyperprolactinemia were excluded. Prolactin level was recorded at the time of
diagnosis, during treatment, and during follow-up. Results The pregnancies
resulted in one spontaneous abortion (3.1%) and 31 live births (96.9%). No
stillbirths, multiple or ectopic pregnancies or trophoblastic disease were
recorded. There was only one malformation (club foot) recorded (3.1%) and
normalisation of prolactin after pregnancy without medical treatment occurred in
12% of patients. Conclusions Fetal exposure to bromocriptine or cabergoline
during pregnancy is not associated with an increased risk of adverse neonatal or
pregnancy disclosures. There is considerable diversity among endocrinologists in
the management of prolactinomas during pregnancy and after birth, which indicates
that there is a need for better consensus and for carefully drawn-up guidelines
to follow.
PMID- 28704853
TI - RBP4/Lp-PLA2/Netrin-1 signaling regulation of cognitive dysfunction in diabetic
nephropathy complicated with silent cerebral infarction.
AB - Aim To investigate the RBP4/Lp-PLA2/Netrin-1 signal regulation of cognitive
function impairment in diabetic nephropathy patients with silent cerebral
infarction (SCI). Methods One-hundred patients newly diagnosed with diabetic
nephropathy patients were included. The patients were divided into SCI group and
NSCI group according to the radiological data. The degrees of cognitive
dysfunction were evaluated. Serum RBP4 concentrations were determined by ELISA
and protein expressions of Lp-PLA2 and Netrin-1 were determined by Western Blot.
Results Compared with NSCI group, the cognitive function of patients in SCI group
was impaired, the concentrations of RBP4 and the expressions of Lp-PLA2 and
Netrin-1 increased (P<0.05). RBP4 concentrations were positively correlated with
the cognitive dysfunction of SCI patients. Moreover, there existed a regression
correlation between them. Conclusion RBP4 may be used as a predictive factor of
diabetic nephropathy patients complicated with SCI and is positively correlated
with cognitive dysfunction. RBP4/Lp-PLA2/Netrin-1 pathway activation may be one
of the occurrence mechanisms in diabetic nephropathy complicated with SCI.
PMID- 28704854
TI - Switching from Premixed Insulin To Basal Insulin Analogue For Type 2 Diabetes and
Role of Dipeptidyl Peptidase-4 Inhibitors.
AB - INTRODUCTION: This study aimed to confirm the usefulness of basal insulin
analogue plus oral antidiabetic drugs (OADs) for type 2 diabetes (T2D) patients
inadequately controlled with premixed insulin with/without OADs and assess the
role of dipeptidyl peptidase-4 (DPP-4) inhibitors within this regimen in clinical
practice. METHODS: Spanish retrospective observational study that included 186
T2D patients with glycosylated hemoglobin (HbA1c) >7% (53 mmol/mol) despite
premixed insulin with/without OADs who had been switched to basal insulin
analogue plus OADs. Study data describing the situation before the treatment
switch and 6 months later was retrospectively retrieved from patients' medical
charts. RESULTS: Switching to a basal insulin plus OADs decreased HbA1c (-1.0%,
p<0.001), fasting (-38.1 mg/dl, p<0.001) and postprandial glycemia (-36.1 mg/dl,
p<0.001), with reduced body weight (-1.1 kg, p<0.001) and hypoglycemic episodes (
17.5%, p<0.001). 68 (36.6%) patients received a basal insulin plus DPP-4
inhibitor+/-metformin and 74 (39.8%) plus metformin only. The DPP-4 inhibitor+/
metformin group showed a greater HbA1c reduction than the metformin group (1.3+/
1.4% vs. 0.9+/-1.0%, p=0.022), with no significant differences between groups in
hypoglycemic episodes. CONCLUSIONS: Basal insulin analogue plus OADs may be a
useful treatment for type 2 diabetes patients inadequately controlled with
premixed insulin. Administering DPP-4 inhibitors within this regimen may
contribute to improve patients' glycemia, with a favorable weight-change profile
and without increasing hypoglycemia risk.
PMID- 28704855
TI - Reduction of HbA1c and diabetes-related distress after intervention in a diabetes
day care clinic in people with type 2 diabetes but not with type 1 diabetes.
AB - OBJECTIVE: The aim of this prospective, longitudinal study was to assess diabetes
related distress in people with diabetes mellitus type 1 (DM1) and type 2 (DM2)
treated for diabetes-related problems and to evaluate, whether distress by
diabetes are reduced after intervention in a diabetes day care clinic (DDC).
METHODS: Diabetes-related burden was assessed with the "Problem Area In Diabetes"
(PAID) questionnaire before (T0), directly after (T1) and 6 months after
intervention (T2) in the DDC in 72 people (18 DM1, 54 DM2) admitted with a
diabetes-specific problem to a DDC in a University department for metabolic
diseases. A PAID score of >=40 was considered as high diabetes-related distress.
RESULTS: The PAID score in people with DM1 was not significantly different
between T0, T1 and T2. Furthermore, neither HbA1c nor insulin dose did change at
T2. In participants with DM2, the PAID score decreased significantly from T0 to
T1 (18.4+/-15.9 vs. 15.4++/- 13.0, p=0.042) and preserved the benefit at T2
(15.0+/-13.3). In addition, there was a significant reduction in HbA1c (-1.2%,
p<0.001) and body weight (-1.3 kg, p=0.038) between T0 and T2. Insulin dose per
day was 15.0 IU/day lower at T1 (p=0.006) and 9.0 IU/day lower at T2 (p=0.212) in
comparison to T0. CONCLUSIONS: Diabetes-related distress was reduced after a
problem-oriented intervention in a DDC in people with DM2 but not with DM1.
Although, all participants at tertiary care level had serious diabetes-specific
problems before intervention, mean PAID score was far under the threshold of 40
points thus distress was low.
PMID- 28704856
TI - Effects of Highly-pure-enriched-cellulose Diet on Digestibility, Lipid Metabolism
and Redox Status in Obese Offspring of Streptozotocin-Induced Diabetic Rats.
AB - The long-term nutritional efficacy of a highly-pure-enriched-cellulose (HPEC)
diet and its effects on lipid metabolism and oxidant/antioxidant status were
investigated in obese offspring of streptozotocin-induced diabetic rats. Diabetes
in pregnant rats was induced by intraperitoneal injection of streptozotocin on
day 5 of gestation. Control pregnant rats were injected with citrate buffer. At
weaning offspring of diabetic and control rats were fed HPEC or control diet,
they were housed individually in metabolic cage for 2 months to investigate the
nutritional efficacy of the diets. Consumption of HPEC diet decrease weight gain
and energy intake, increase fecal weight and reduce lipid and protein
digestibility; however, these diet had no effect on protein utilization, and
nitrogen balance remained positive which confirms that HPEC diet had no
significant long-term nutritional risks. Indeed for obese offspring from diabetic
rats, these diet associated with high satiety promote weight loss, and provide
reasonable glycemic control, these diet also lower blood lipids concentration and
correct the imbalance of oxidant/antioxidant system. HPEC diet had a protective
effect against long-term metabolic abnormalities associated with macrosomia.
PMID- 28704857
TI - The Real-Life Effectiveness and Care Patterns of Type 2 Diabetes Management in
Greece.
AB - AIM: To investigate the prevalence of hypoglycaemia during sulfonylurea (SU)
treatment of type 2 diabetes mellitus (T2DM) in Greece and its influence on
glycaemic control, treatment adherence and quality of life (QoL). PATIENTS AND
METHODS: This was a retrospective cross-sectional study. We included 383 T2DM
patients >=30 years old on treatment with SU in monotherapy or in combination
with metformin for at least 6 months. Patients were requested to fill in
retrospective questionnaires on hypoglycaemia experience, adherence, weight gain
and lifestyle/behavioural factors along with QoL (EQ-5D-3L), treatment
satisfaction (TSQM), and fear of hypoglycaemia (HFS-II Worry scale). RESULTS:
HbA1c<7% was found in 161 (42.0%) patients. In total, 165 (43.1%) patients
reported hypoglycaemic symptoms during the previous 6 months: 41.6% (67/161) of
those with HbA1c <7% and 44.1% (98/222) of those with HbA1c >=7%. Glycaemic
control was achieved by 43.1% (94/218) of patients without hypoglycaemia and
50.0% (41/82), 36.8% (25/68) and 6.7% (1/15) of patients with mild, moderate or
severe hypoglycaemia, respectively (p=0.013). In multivariate analysis, both
occurrence (none vs. mild/moderate/severe) and severity (none vs. mild vs.
moderate vs. severe) of hypoglycaemia were significantly associated with impaired
global treatment satisfaction (p=0.002 and p<0.0001 respectively) and HFS-II
Worry scale scores (both p<0.0001), while lower QoL (EQ-5D (UK) Index) was
related to hypoglycaemia severity (p=0.024) only. Finally, treatment adherence
was associated with increased (none/mild vs. moderate/severe) hypoglycaemia
severity in univariate analysis (p=0.019). CONCLUSION: A high prevalence of
patient treated with SU reported hypoglycaemia in Greek healthcare settings with
negative effects on treatment satisfaction, patient worry and adherence. Severity
of hypoglycaemic symptoms was associated with reduced glycaemic control.
PMID- 28704858
TI - Comparison of HbA1c Measurements using 3 Methods in 75 Patients Referred to One
Outpatient Department.
AB - OBJECTIVE: HbA1c is the most important surrogate parameter to assess the quality
of diabetes care and is also used for the diagnosis of diabetes mellitus (DM)
since 2010. We investigated the comparability of 3 HbA1c methods in the city of
Jena (Germany). METHODS: The HbA1c determination was carried out in 50 healthy
subjects and 24 people with DM (age 51.2+/-16.3 years, HbA1c 6.8+/-2.2%) with 3
different hemoglobin A1c testing methods at 4 locations in one city. Our
laboratory (HPLC method) served as a reference for comparing the results. All
methods are IFCC standardized and all devices are certified by the
interlaboratory test. RESULTS: The mean HbA1c of people without diabetes was:
laboratory A (TOSOH G8, HPLC) 5.7+/-0.3%; laboratory B (TOSOH G8, HPLC) 5.5+/
0.3%, laboratory C (VARIANT II) 5.2+/-0.3%; laboratory D (COBAS INT.) 5.6+/-0.3%.
All differences are significant (p=0.001).The mean HbA1c of patients with mild to
moderate elevated HbA1c was: Laboratory A 7.5+/-0.9%; B 7.3+/-1.0%; C 7.0+/-0.9%;
D 7.5+/-1.1%. Differences are significant (p=0.001) except between laboratory A
and D (p=0.8).The mean HbA1c of patients with massively increased HbA1c was:
laboratory A 11.5+/-1.8%; laboratory B 11.4+/-1.8%; laboratory C 10.8+/-1.6%;
laboratory D 11.5+/-1.5%. Differences between laboratory A and C, as well as
between C and D were significant (p=0.001). CONCLUSION: The mean IFCC
standardized HbA1c from 75 people differs by up to 0.5% absolute between 4
laboratories. This difference is clinically significant and may lead to
misdiagnosis and wrong treatment decisions, while HbA1c value from one patient
were analyzed in different laboratories within a short time.
PMID- 28704865
TI - ?
PMID- 28704860
TI - [Renal Involvement in Malignant Lymphoproliferative Diseases: CT Imaging
Pattern].
PMID- 28704871
TI - ?
PMID- 28704872
TI - ?
PMID- 28704873
TI - ?
PMID- 28704875
TI - Sonographic and Doppler Sonographic Diagnosis of Neonatal Ischemic Stroke.
AB - Children are particularly at risk for stroke in the neonatal period. 1/3 of all
strokes in children occur during the perinatal period. The incidence of perinatal
stroke is 1:4000. A differentiation is made between ischemic stroke and
hemorrhagic stroke. Ischemic strokes are caused by arterial occlusion due to
thrombosis or embolism. As a result of the nonspecific clinical symptoms in this
age group, diagnosis is usually made too late. The only relatively specific
symptom is focal cerebral seizure during the first week of life. Therefore,
stroke should be ruled out by diagnostic imaging in the case of any seizure in
the first days of life. Although the diagnostic method of choice is MRI, it is
not always available. Most neonatal ischemic strokes can be detected with high
resolution duplex ultrasound. On ultrasound, ischemic stroke appears as a wedge
shaped focal increase in echogenicity in the supply region of an artery,
typically the middle cerebral artery. The corresponding arterial inflow can be
visualized with duplex ultrasound and measured with spectral Doppler. Doppler
ultrasound can be used to differentiate between complete occlusion and severe
stenosis. The success of therapeutic measures can be determined in the further
course with Doppler ultrasound on the basis of the recanalization of vessels and
the morphological consequences of stroke (cyst formation due to liquefactive
necrosis).
PMID- 28704876
TI - Mesenteric Masses on 2D Mode and Contrast-Enhanced Ultrasound: A Retrospective
Study in 69 Patients.
AB - PURPOSE: Detection of mesenteric masses (MM) by 2 D ultrasound often causes a
diagnostic dilemma, and histological confirmation is required for definite
diagnosis. The value of contrast-enhanced ultrasound (CEUS) for the diagnosis of
MMs has not been investigated before. Here, we retrospectively evaluate 2D-mode
and CEUS patterns of 69 patients with histologically confirmed MMs. MATERIALS AND
METHODS: Between January 2006 and January 2016, n = 69 patients were included in
the study. Histopathological data, clinical data, 2D-mode ultrasound and CEUS
enhancement were retrospectively analyzed. RESULTS: More than half of the MMs (n
= 47/69, 68 %) revealed a malignant histology. The size of the MM, inflammation
markers and clinical symptoms did not correlate with the histological outcome. 2
D mode revealed n = 46 (67 %) lesions as hypoechoic, n = 14 (20 %) as
hyperechoic, and n = 9 (13 %) with a complex echo pattern. Hypoechogenicity and
complex echo patterns as well as regular borders of MMs were significantly
associated with malignancy (p < 0.05). On CEUS, malignant MMs showed arterial
hyperenhancement (n = 11/47, 23 %), isoenhancement (n = 25/47, 52 %) and
hypoenhancement (n = 7/47, 15 %). The majority of malignant MMs (n = 42/47, 89 %)
revealed parenchymal hypoenhancement. Benign masses revealed arterial
hyperenhancement in n = 1/22 (5 %), isoenhancement in n = 8/22 (36 %), and
hypoenhancement in n = 10/22 (45 %). The majority of lesions showed parenchymal
hypoenhancement (n = 19/22, 86 %). CONCLUSION: Hypoechogenicity and complex
echogenicity in 2 D mode, irregular borders, and parenchymal wash-out were more
often associated with malignancy. However, CEUS did not help to subclassify
malignant MMs according to their histological entity.
PMID- 28704877
TI - Safety Concerns regarding article: Reliability and Validity of a Self-paced
Cardiopulmonary Exercise Test in Post-MI Patients. L. A. Jenkins, A. Mauger, J.
Fisher, J. Hopker. Int J Sports Med 2017; 38: 300-306.
PMID- 28704878
TI - Evaluation of Risk in Research must be Judged on Evidence, not Personal Opinion.
PMID- 28704879
TI - Clinical Study to Analyze the Intramuscular Anatomy of Musculocutaneous
Perforators of Anterolateral Thigh Flaps.
PMID- 28704880
TI - Left Ventricular Adaptation to 12 Weeks of Indoor Cycling at the Gym in Untrained
Females.
AB - Cross-sectional studies provide evidence of larger cardiac dimensions and mass in
endurance trained than in untrained females. Much less is known regarding
adaptations in cardiac function following training in untrained subjects. We
aimed to study left ventricular (LV) adaptation to indoor cycling in previously
untrained females, in regard of LV dimensions, mass and function. 42 sedentary
females were divided into 2 equally sized groups, either training indoor cycling
at regular classes at a local gym for 12 weeks, in average 2.6 times per week, or
maintaining their sedentary lifestyle. Echocardiography at rest and a maximal
exercise test were performed before and after the intervention. Exercise capacity
increased in average 16% in the exercise group (p<0.001), together with decreased
heart rate at rest (p<0.05) and at 120 watts steady-state (p<0.001). There were
no difference in systolic or diastolic function following the intervention and
minimal increases in LV internal diameter in diastole (+1 mm, p<0.01). LV mass
was unchanged with training (137+/-25 vs. 137+/-28 g, p=0.911). Our findings
indicate that attending indoor cycling classes at a gym 2-to-3 times per week for
12 weeks is enough to improve exercise capacity, while a higher volume of
training is required to elicit cardiac adaptations.
PMID- 28704881
TI - Cardiovascular and Autonomic Responses to a Maximal Exercise Test in Elite
Youngsters.
AB - To analyze cardiovascular and autonomic responses in elite youngsters, 13 male
cyclists (15.43+/-0.51 years) performed a graded-test until voluntary exhaustion.
Oxygen consumption (VO2), blood lactate (BLa), arterial oxygen saturation (SaO2),
respiratory exchange ratio (RER) and rating of perceived exertion (RPE) were
collected, while heart rate (HR) was registered for heart rate variability (HRV)
analyses, looking for linear and nonlinear comparisons. Cyclists reached maximal
exertion [RPE: 19.14+/-0.94; BLa: 8.92+/-2.51 mmol.L-1; RER: 1.04+/-0.03; SaO2:
92.43+/-2.5%] and high-level performance (4.41+/-0.46 W.Kg-1; 60.77+/-6.87
ml.Kg.min-1) once over 95% of age-predicted HRmax. VO2 and RPE increased, and RR
intervals (RRi) decreased (p<0.005), whereas only the short-term scaling exponent
of the Detrended Fluctuation Analysis technique (DFA1) displayed similar adaptive
changes regarding intensity (p=0.011). After controlling for W.Kg-1 and RRi,
DFA1100% (0.260+/-0.084) showed large-negative correlations with VO2max (r=-0.83;
p<0.05) and RPEmax (r=-0.79; p<0.05), suggesting a strong association between the
reduction in self-similar properties of the cardiac signal and the capacity to
elicit at maximum in youths. Overall-HRV (lnRMSSD) and short-term variability
(lnSD1) did not show any association at maximum, or significant differences
regarding intensity. DFA1 might reflect ANS-CNS linkage related to cardiac
respiratory controls through exercise, becoming a complementary criterion for
VO2max testing in youths.
PMID- 28704882
TI - Neuromuscular Adaptations to Combined Strength and Endurance Training: Order and
Time-of-Day.
AB - The present study examined the effects of 24 weeks of morning vs. evening same
session combined strength (S) and endurance (E) training on neuromuscular and
endurance performance. Fifty-one men were assigned to the morning (m) or evening
(e) training group, where S preceded E or vice versa (SEm, ESm, SEe and ESe), or
to the control group. Isometric force, voluntary activation, EMG and peak wattage
during the maximal cycling test were measured. Training time did not
significantly affect the adaptations. Therefore, data are presented for SEm+e
(SEm+SEe) and ESm+e (ESm+ESe). In the morning, no order specific gains were
observed in neuromuscular performance. In the evening, the changes in isometric
force (SEm+e 15.9+/-16.7%, p=0.001; ESm+e 4.1+/-12.2%, p=0.615) and EMG (SEm+e
38.3+/-31.7%, p=0.001; ESm+e 14.67+/-36.44%, p=0.486) were larger (p=0.014) in
SEm+e than in ESm+e and in voluntary activation larger (p=0.026) in SEm+e
compared to controls. Peak wattage increased in the morning (SEm+e 15.9+/-9.2%,
ESm+e 22.0+/-7.0%; p<0.001) and evening (SEm+e 16.3+/-7.2%, ESm+e 21.0+/-9.0%;
p<0.001) but were larger (p<0.05) in ESm+e. The current training program led to
greater neuromuscular adaptations when SE-training was performed in the evening,
whereas the ES-training provided more optimal conditions for endurance
performance adaptations both in the morning and evening.
PMID- 28704883
TI - Validity and Reliability of a New Device (WIMU(r)) for Measuring Hamstring Muscle
Extensibility.
AB - The aims of the current study were 1) to evaluate the validity of the WIMU(r)
system for measuring hamstring muscle extensibility in the passive straight leg
raise (PSLR) test using an inclinometer for the criterion and 2) to determine the
test-retest reliability of the WIMU(r) system to measure hamstring muscle
extensibility during the PSLR test. 55 subjects were evaluated on 2 separate
occasions. Data from a Unilever inclinometer and WIMU(r) system were collected
simultaneously. Intraclass correlation coefficients (ICCs) for the validity were
very high (0.983-1); a very low systematic bias (-0.21 degrees --0.42 degrees ),
random error (0.05 degrees -0.04 degrees ) and standard error of the estimate
(0.43 degrees -0.34 degrees ) were observed (left-right leg, respectively)
between the 2 devices (inclinometer and the WIMU(r) system). The R2 between the
devices was 0.999 (p<0.001) in both the left and right legs. The test-retest
reliability of the WIMU(r) system was excellent, with ICCs ranging from 0.972
0.995, low coefficients of variation (0.01%), and a low standard error of the
estimate (0.19-0.31 degrees ). The WIMU(r) system showed strong concurrent
validity and excellent test-retest reliability for the evaluation of hamstring
muscle extensibility in the PSLR test.
PMID- 28704884
TI - Prone Hip Extension Muscle Recruitment is Associated with Hamstring Injury Risk
in Amateur Soccer.
AB - 'Core stability' is considered essential in rehabilitation and prevention.
Particularly with respect to hamstring injury prevention, assessment and training
of lumbo-pelvic control is thought to be key. However, supporting scientific
evidence is lacking. To explore the importance of proximal neuromuscular function
with regard to hamstring injury susceptibility, this study investigated the
association between the Prone Hip Extension (PHE) muscle activation pattern and
hamstring injury incidence in amateur soccer players. 60 healthy male soccer
players underwent a comprehensive clinical examination, comprising a range of
motion assessments and the investigation of the posterior chain muscle activation
pattern during PHE. Subsequently, hamstring injury incidence was recorded
prospectively throughout a 1.5-season monitoring period. Players who were injured
presented a PHE activation pattern that differed significantly from those who did
not. Contrary to the controls, hamstring activity onset was significantly delayed
(p=0.018), resulting in a shifted activation sequence. Players were 8 times more
likely to get injured if the hamstring muscles were activated after the lumbar
erector spinae instead of vice versa (p=0.009). Assessment of muscle recruitment
during PHE demonstrated to be useful in injury prediction, suggesting that
neuromuscular coordination in the posterior chain influences hamstring injury
vulnerability.
PMID- 28704885
TI - Submaximal Markers of Fatigue and Overreaching; Implications for Monitoring
Athletes.
AB - The regular monitoring of athletes is important to fine-tune training and detect
early symptoms of overreaching. Therefore the aim of this study was to determine
if a noninvasive submaximal running test could reflect a state of overreaching.
14 trained runners completed a noninvasive Lamberts Submaximal Running Test, one
week before and 2 days after finishing an ultramarathon, and delayed onset of
muscle soreness and the daily analysis of life demands for athletes questionnaire
were also captured. After the ultramarathon, submaximal heart rate was lower at
70% (-3 beats) and 85% of peak treadmill running speed (P<0.01). Ratings of
perceived exertion were higher at 60% (2 units) and 85% (one unit) of peak
treadmill running speed, while 60-second heart rate recovery was significantly
faster (7 beats, P<0.001). Delayed Onset of Muscle Soreness scores and the number
of symptoms of stress (Daily Analysis of Life Demands for Athletes) were also
higher after the ultramarathon (P<0.01). The current study shows that the
Lamberts Submaximal Running Test is able to reflect early symptoms of
overreaching. Responses to acute fatigue and overreaching were characterized by
counterintuitive responses, such as lower submaximal heart rates and faster heart
rate recovery, while ratings of perceived exertion were higher.
PMID- 28704886
TI - Tensiomyographic Assessment of Muscle Contractile Properties in 9- to 14-Year Old
Children.
AB - While there are numerous data on the skeletal muscle fiber type composition in
adults, little is known about the changes in fiber type composition and
contractile properties during maturational growth in children. Using noninvasive
tensiomyography, we measured contraction time (Tc), an indirect estimate of the
myosin heavy chain I (MHC-I) proportion, to assess the longitudinal changes of
the biceps brachii (BB), biceps femois (BF), vastus lateralis (VL), and erector
spinae (ES) muscles in 53 boys and 54 girls. The children were 9 years at the
start of the study and returned for 5 follow-up measurements until the age of 14
years. The ES has the shortest and the BF has the longest Tc. The VL and ES of
boys have shorter Tc than those of girls. When applying the relationship between
proportion of MHC-I and Tc established in adults to children's TMG data, we found
a slow-to-fast transition in the VL between, at least, the ages of 6 to 10 years,
when it stabilized to adult proportions. Regular participation in sports was
associated with a faster BF, but not in the VL. Our data represents a first non
invasive indication of the developmental changes in muscle fiber type composition
in children.
PMID- 28704887
TI - How bird clades diversify in response to climatic and geographic factors.
AB - While the environmental correlates of global patterns in standing species
richness are well understood, it is poorly known which environmental factors
promote diversification (speciation minus extinction) in clades. We tested
several hypotheses for how geographic and climatic variables should affect
diversification using a large dataset of bird sister genera endemic to the New
World. We found support for the area, evolutionary speed, environmental
predictability and climatic stability hypotheses, but productivity and
topographic complexity were rejected as explanations. Genera that had accumulated
more species tend to occupy wider niche space, manifested both as occurrence over
wider areas and in more habitats. Genera with geographic ranges that have
remained more stable in response to glacial-interglacial changes in climate were
also more species rich. Since many relevant explanatory variables vary
latitudinally, it is crucial to control for latitude when testing alternative
mechanistic explanations for geographic variation in diversification among
clades.
PMID- 28704888
TI - Assessing musical ability quickly and objectively: development and validation of
the Short-PROMS and the Mini-PROMS.
AB - The study of musical ability has gained considerable traction across disciplines
in recent years. In comparison, less effort has been invested in the development
of sound measures of musical ability. To redress this gap, we conducted four
studies to empirically validate two brief measures derived from the Profile of
Music Perception Skills (PROMS)-an exceptionally inclusive battery of musical
abilities that takes about 1 h to complete. In the Short-PROMS, test duration was
reduced to less than half an hour by substantially reducing the number of trials
per subtest. In the Mini-PROMS, the number of subtests was reduced to four,
resulting in a battery that takes 15 min to complete. Both measures exhibited
good internal consistency and retest reliability. Support for convergent,
discriminant, and criterion validity was found across the studies. Additional
strengths of the new instruments include their suitability for online
administration and a feature called Modular PROMS, which offers researchers the
possibility to request customized batteries that may include any combination of
the subtests. The role of refining objective assessment instruments in research
on music and the mind is discussed.
PMID- 28704889
TI - Cyclodextrins increase phytosterol and tocopherol levels in suspension cultured
cells obtained from mung beans and safflower.
AB - In this work, suspension-cultured cells of mung beans and safflower were used in
order to analyze the effect of methyl jasmonate and/or cyclodextrins, on
bioactive compound production such as phytosterols and tocopherols. The results
indicated that mung bean suspension-cultured cells produced higher amount of
total phytosterols and tocopherols. In particular, mung bean suspension-cultured
cells produced almost 220-fold higher levels of tocopherols than safflower
suspension-cultured cells in the best conditions. However, while cyclodextrins
were able to enhance extracellular production of phytosterols, in the case of
tocopherols, they only increased their intracellular accumulation. Our results
showed that mung bean cells could be used as a highly efficient system for the
production of phytosterols and tocopherols which have a wide range of biological
activities. (c) 2017 American Institute of Chemical Engineers Biotechnol. Prog.,
33:1662-1665, 2017.
PMID- 28704890
TI - Analysis of Subway Interior Noise at Peak Commuter Time.
AB - BACKGROUND AND OBJECTIVES: Although mass transit systems are convenient and
efficient for urban people, little attention has been paid to the potential
hearing hazard from their noise. The purpose of the current study was to measure
and analyze levels of subway interior noise at peak commuter times and to provide
information about commuters' daily dose of noise exposure. MATERIALS AND METHODS:
To measure the subway interior noise, nine subway lines inside Seoul (i.e., lines
1-9) and six lines surrounding the capital city area (i.e., Central, Bundang,
Sinbundang, Incheon, Gyeongui, and Gyeongchun) were chosen. The noise was
measured and recorded by a sound level meter for two-hour periods in the morning
and evening. RESULTS: 1) In the LZeq analysis, the average noise level of all 15
lines was 72.78 dB; the maximum and minimum noise levels were 78.34 and 62.46 dB,
respectively. The average noise level of the nine lines inside Seoul was 73.45
dB, which was 1.68-dB louder than that of the six lines surrounding the capital
city area. 2) Based on the LZeq analysis of 33 measured frequencies, 12.5 Hz was
the highest frequency and 20,000 Hz was the lowest. 3) There was no remarkable
difference in the level of subway interior noise between morning and evening peak
commuter times. CONCLUSIONS: We concluded that the level of subway interior noise
was not loud enough for commuters to incur noise-induced hearing loss.
Regardless, environmental noise control efforts in the subway system might be
needed for commuters who take a subway every day.
PMID- 28704891
TI - Mastoid Vibration Reduces Ipsilesional Shift of Subjective Visual Horizontal in
Patients with Acute Stage of Unilateral Vestibulopathy.
AB - BACKGROUND AND OBJECTIVES: To investigate effect of the vibration on subjective
visual horizontal (SVH) in patients with acute stage of unilateral
vestibulopathy. SUBJECTS AND METHODS: Twenty-five unilateral vestibulopathy
patients which analyzed into 42 cases at different time points and suffered from
spinning vertigo for more than 24 hours without hearing loss and neurologic
abnormality were enrolled. Thirteen subjects with spontaneous nystagmus (>3
degree/sec; averaged symptom onset <1 week) at the time of SVH measurement were
classified into the acute unilateral vestibulopathy group (aVU). The other 29
subjects without spontaneous nystagmus were classified into the compensated
vestibulopathy group (cVU). SVH was performed with vibration at either mastoid or
sterocleidomastoid muscle. RESULTS: In the analysis of overall subjects,
vibration did not significantly change the degree of shift of SVH. However,
analyzed by group, the shift of SVH with vibration at ipsilesional mastoid was
significantly decreased than baseline in aVU (p<0.05). The shift of SVH with
vibration at contralesional mastoid was significantly increased than baseline in
cVU (p=0.05). CONCLUSIONS: The shift of SVH due to vibration in acute stage of
unilateral vestibulopathy showed reduction of the shift, while in compensated
stage it showed increase of the shift.
PMID- 28704892
TI - Is Electrocochleography Still Helpful in Early Diagnosis of Meniere Disease?
AB - BACKGROUND AND OBJECTIVES: Despite the extensive research for the Meniere's
disease (MD), it's pathophysiology still remains uncertain and questionable among
scientists. Clinical symptoms and audiometric tests form the basis for the
diagnosis. Nevertheless the differential diagnosis can be extremely challenging,
due to subjective and not specific results. Incorrect diagnosis is most likely
and for this reason there is a great demand for objective and reliable tests.
SUBJECTS AND METHODS: The presence of endolymphatic hydrops is necessary
condition but non enough for the diagnosis. In this study we analyze
retrospectively the summating potentials (SP)/action protentials (AP) ratio from
peritympanic electrocochleography in 34 patients,divided in two groups (13
patients classified as defined MD and 21 patients classified as probable MD). The
purpose was to identify the utility of the exam so to be able to achieve an early
defined diagnosis. Furthermore our intention was to obtain an objective test,
besides the clinical criteria currently in use for the diagnosis and the
classification of the MD. RESULTS: The analysis of the SP/AP results shows high
predictability for the MD (positive in six out of seven cases with a sensitivity
greater than 80%). CONCLUSIONS: Our study demonstrates a satisfactory sensibility
percentage in recurrent defined MD presentation (>80%). Early identification of
MD can lead to an early treatment and control of the progression of the disease.
Furthermore it could be a valuable instrument for the follow up and evaluation of
the patients classified as probable MD in accordance with the criteria of the
American Academy of Otolaryngology-Head and Neck Surgery (1995).
PMID- 28704893
TI - Clinical Characteristics of Idiopathic Epidermoid and Dermoid Cysts of the Ear.
AB - BACKGROUND AND OBJECTIVES: Epidermoid and dermoid cysts are benign cystic
lesions, lined by ectodermal squamous epithelium. They are not common in the head
and neck areas, which constitute ~7% of all cases of epidermoid and dermoid
cysts. The aim of this study was to investigate the clinical characteristics of
epidermoid and dermoid cysts that developed around the ear. SUBJECTS AND METHODS:
The clinical records were retrospectively reviewed for patients confirmed
histologically as idiopathic epidermoid and dermoid cysts of the ear from January
2011 to December 2015. RESULTS: Total 15 cases consisted of 14 epidermoid cysts
and only 1 dermoid cyst. There were 11 males and 4 females (mean age of 37.8+/
16.8 years old). Right side was 7 cases and left was 8. The cyst was located at
the lobule in 4 cases, at the ear canal in 4 cases, at the preauricular area in 4
cases, and at the postauricular area in 3 cases. In cases of epidermoid cysts,
there was no significant difference in age, sex, and size according to the
location. Patients with cysts on helix were younger than others. CONCLUSIONS:
This study demonstrated that most cutaneous cysts developing around the ear were
epidermoid cysts and there was no site preference for occurrence of epidermoid
cysts.
PMID- 28704894
TI - Factors Affecting Sentence-in-Noise Recognition for Normal Hearing Listeners and
Listeners with Hearing Loss.
AB - BACKGROUND AND OBJECTIVES: Despite amplified speech, listeners with hearing loss
often report more difficulties understanding speech in background noise compared
to normalhearing listeners. Various factors such as deteriorated hearing
sensitivity, age, suprathreshold temporal resolution, and reduced capacity of
working memory and attention can attribute to their sentence-in-noise problems.
The present study aims to determine a primary explanatory factor for sentence-in
noise recognition difficulties in adults with or without hearing loss. SUBJECTS
AND METHODS: Forty normal-hearing (NH) listeners (23-73 years) and thirty-four
hearing-impaired (HI) listeners (24-80 years) participated for experimental
testing. For both NH and HI group, the younger, middle-aged, older listeners were
included. The sentence recognition score in noise was measured at 0 dB signal-to
noise ratio. The ability of temporal resolution was evaluated by gap detection
performance using the Gaps-In-Noise test. Listeners' short-term auditory working
memory span was measured by forward and backward digit spans. RESULTS: Overall,
the HI listeners' sentence-in-noise recognition, temporal resolution abilities,
and digit forward and backward spans were poorer compared to the NH listeners.
Both NH and HI listeners had a substantial variability in performance. For NH
listeners, only the digit backward span explained a small proportion of the
variance in their sentence-in-noise performance. For the HI listeners, all the
performance was influenced by age, and their sentence-in-noise difficulties were
associated with various factors such as high-frequency hearing sensitivity,
suprathreshold temporal resolution abilities, and working memory span. For the HI
listeners, the critical predictors of the sentence-in-noise performance were
composite measures of peripheral hearing sensitivity and suprathreshold temporal
resolution abilities. CONCLUSIONS: The primary explanatory factors for the
sentence-in-noise recognition performance differ between NH and HI listeners.
Factors affecting sentence-in-noise recognition performance differed between NH
and HI listeners. The working memory was the primary predictor of the sentence-in
noise scores for the NH individuals. In contrast, a combination of factors seemed
to contributed to speech-in-noise understanding for the HI listeners. Given this,
we must be careful not to generalize findings from the NH listeners to the HI
individuals.
PMID- 28704895
TI - Comparisons in Outcome and Subject Comfort between Rotation Chair Systems.
AB - BACKGROUND AND OBJECTIVES: A rotation chair test has been used to evaluate the
function of the horizontal semicircular canals. Currently, two chair systems
according to the presence of cylindrical darkroom are used in a clinic setting.
However, it has not been thoroughly investigated whether one system is superior
to the other system or not. In this study, we aimed to compare test outcomes and
subject convenience between two systems. SUBJECTS AND METHODS: Twenty subjects
with no history of otologic disease were enrolled. Subjects were tested with two
systems: system [A] with a cylindrical chamber and system [B] with no chamber.
The results of sinusoidal harmonic acceleration (SHA), step velocity (SV), and
visual fixation (VFX) tests were compared between the systems. Subject
convenience was assessed with a questionnaire survey and results were compared
between the systems. RESULTS: There were no significant differences in gain or
asymmetry in SHA test between the systems. However, the phase of system [A] was
significantly lower than that of system [B] at 0.16 Hz. There was no significant
difference between the systems in directional preponderance (DP) gain or DP time
constant. Regarding the VFX test, gain was higher in system [A] than system [B].
Subjects reported less stuffiness and less anxiety with system [B] than system
[A], while preferring the system [A] goggles. CONCLUSIONS: A rotation chair
system without a darkroom can provide a more comfortable experience for subjects
in terms of stuffiness and anxiety, while showing comparable results in SHA and
SV tests with a darkroom system.
PMID- 28704896
TI - Long Term Speech Perception Outcomes of Cochlear Implantation in Gap Junction
Protein Beta 2 Related Hearing Loss.
AB - BACKGROUND AND OBJECTIVES: The mutation of the gap junction protein beta 2 (GJB2)
gene is the predominant cause of autosomal recessive non-syndromic hearing loss.
The purpose of this study was to evaluate the speech perception outcome after
cochlear implantation according to the presence of a GJB2 mutation. SUBJECTS AND
METHODS: During the period from March 2004 to February 2005, 38 patients
underwent cochlear implantation at Asan Medical Center. Genetic factors and
speech perception were evaluated in all subjects, and the patients were grouped
according to the presence of a GJB2 mutation. The two groups were carefully
matched according to the age at cochlear implantation. We analyzed four mutations
in the GJB2 gene: 35delG, 167delT, 235delC, and E114G. Speech perception outcomes
were measured using the open set, 1 and 2 syllables, the comprehension test, the
Meaningful Auditory Integration Scale, the categories of auditory performance,
and the Speech Intelligibility Rating scores. The evaluations were performed
before the operation, 6 and 12 months thereafter, and then annually up to nine
years after cochlear implantation. RESULTS: Fifteen patients had bi-allelic GJB2
mutations (11 with E114G and 4 with 235delC), whereas the remaining 23 had wild
type alleles. For the age-matched analysis, 14 patients were selected and divided
into two groups of 7 subjects each: GJB2 mutation and no mutation (i.e., deafness
of unknown origin). Overall, all patients showed improvement of speech perception
outcome after cochlear implantation. There was no difference in the improvement
between patients with and without GJB2 mutations at the 5-year and 9-year follow
up. The pattern of improvement throughout the duration of the follow-up also
showed no difference between the two groups. CONCLUSIONS: Similar outcomes of
speech perception are expected after cochlear implantation in pediatric patients
with or without GJB2 mutation.
PMID- 28704897
TI - Comparison of Free-Beam- and Fiber-Type CO2 Laser Delivery Systems in Stapes
Surgery.
AB - BACKGROUND AND OBJECTIVES: A free-beam-type CO2 laser, which use a
micromanipulator mounted on a microscope as the delivery system, has the merit of
not being affected by hand tremor at the time of shooting. However, this delivery
system has several disadvantages, including a restricted operation range and a
risk of incorrect focusing. A fiber-type CO2 laser uses a hand-held delivery
system and has the opposite merits and demerits. We compared the results of
stapes surgery with free-beam and fiber type delivery systems. SUBJECTS AND
METHODS: The study enrolled 36 patients who underwent stapedotomy with free-beam-
(n=26) or fiber- (n=10) type CO2 lasers. The air-bone (AB) gap closure, bone
conduction (BC) change, and operating time were evaluated. The AB gap closure was
calculated by subtracting the preoperative BC thresholds from the postoperative
air conduction thresholds. The BC change was calculated by subtracting the
postoperative BC thresholds from the preoperative BC thresholds. RESULTS: The
mean operating time was significantly (p=0.035) shorter in the fiber-type group
(72.5+/-8.2 min) than in the free-beam-type group (80.5+/-11.4 min). The mean AB
gap closure did not differ significantly (p=0.297) between the free-beamand fiber
type groups (5.8+/-10.1 and 1.4+/-6.8 dB, respectively). The mean BC change did
not differ significantly (p=0.873) between the free-beam- and fiber-type groups
(2.4+/-6.9 and 2.8+/-5.3 dB, respectively). The hearing outcomes did not differ
significantly between the two groups. CONCLUSIONS: Operating times were
significantly shorter using the fiber-type CO2 laser, while hearing outcomes did
not differ significantly between the two groups.
PMID- 28704898
TI - A Case of Auditory Neuropathy Caused by Pontine Hemorrhage in an Adult.
AB - A pontine hemorrhage can evoke several neurological symptoms because the pons
contains various nuclei and nerve fibers. Hearing loss can develop as a result of
a pontine hemorrhage because there is an auditory conduction pathway in the
cochlear nucleus of the pons. However, very few cases of hearing loss caused by
pontine lesions have been reported, and there have been no reports of auditory
neuropathy that developed following a pontine hemorrhage. Recently we had a
patient who experienced a nontraumatic pontine hemorrhage who was diagnosed with
auditory neuropathy. The 34-year-old male patient was admitted to the emergency
department with sudden alteration of mental status. His brain computed
tomographic imaging revealed a hemorrhage in the central pons. He complained of
hearing difficulties after his mental status recovered through conservative
treatment, but a pure-tone audiogram showed very mild hearing loss in both ears.
Further hearing tests using otoacoustic emissions, which showed normal responses,
and auditory brainstem responses, which showed no waveforms at maximum stimulus
intensity, revealed that his hearing difficulties were caused by auditory
neuropathy. This case implies that the threshold of sound detection can be
preserved in patients with pontine hemorrhage who complain of hearing
difficulties. Auditory neuropathy should be considered as a possible cause of
hearing difficulties in these patients and appropriate hearing tests should be
performed.
PMID- 28704899
TI - Cochlear Fistula in Chronic Otitis Media without Cholesteatoma.
AB - Cochlear fistula in the chronic otitis media (COM) without cholesteatoma is an
extremely rare with only a few cases reported in the literature to this date. We
describe a case of cochlear fistula observed in a female with COM without
cholesteatoma. This report presents the first clinical case of a transtympanic
iatrogenic trauma by habitual cotton swabs probably causing cochlear fistula.
PMID- 28704900
TI - Examination of an Audiologist's Response to Patient's Expression of Symptoms: A
Pilot Study.
AB - : This pilot study explores audiologist-patient interactions during initial
evaluations or consultations. In particular, an audiologist's response to patient
symptoms is examined. Conversations between audiologist and patients were
recorded using a digital recorder, which were transcribed, and analyzed using the
Codes for Human Analysis of Transcripts and Child Language Analysis computer
programs. Mean length of turn and frequency of utterances related to explicit
discussion or description of symptoms or the patient's interpretation of symptoms
was determined. STUDY SAMPLE: six audiologist-patient interactions were recorded
and transcribed. A single audiologist was used for this pilot investigation.
Results suggest that during the initial audiological consultations related to
hearing difficulties the audiologist produced more utterances related to explicit
description of the symptoms, whereas when during the sessions about complex
disorder and hearing aid consultation the audiologist produced more utterances
related to the patient's interpretation of the symptoms. Also, a more equitable
distribution of words and utterances per turn are observed during the initial
consultation about hearing difficulties when compared to complex disorders and
hearing aid consultation sessions where the audiologist was dominant within the
interaction. This preliminary study reveals unique insights to audiologist's
communication behavior during audiology consultation session. Efforts are needed
to educate and promote appropriate communication between audiologists' and
patients, which could result in increased patient satisfaction.
PMID- 28704901
TI - The Gaps between Knowing and Doing in Hearing Aid Fitting Management.
AB - Evidence based practice has become an important aspect in many healthcare
provisions to improve patient outcomes. Investigating the gaps between knowing
and doing in audiology practice will provide future directions for successful
service delivery. The purpose of this study was to explore "know-do" gaps related
to professional awareness and attitude in hearing aid fitting management (HAFM)
by analyzing data of a questionnaire. It consisted of 22 questions focusing on 11
HAFM components. Each component had two sub-questions involving levels of the
importance and practice for HAFM. Respondents answered each question based on
subjective judgments for their own hearing aid fitting services with a Visual
Analogue Scale. A total of 51 responses from hearing care professionals were
collected and the scores for knowing and doing were compared. The results showed
overall high scores in doing and knowing responses; however, there were
significant "know-do" gaps demonstrating higher knowing scores than doing scores
across all HAFM components. The largest "know-do" gaps were observed in three
components mostly implemented during follow-up sessions which indicate the need
to improve their corresponding services and practical guidelines emphasizing the
follow-up services.
PMID- 28704902
TI - Continuous Passaging of a Recombinant C-Strain Virus in PK-15 Cells Selects
Culture-Adapted Variants that Showed Enhanced Replication but Failed to Induce
Fever in Rabbits.
AB - Classical swine fever virus (CSFV) is the etiologic agent of classical swine
fever, a highly contagious disease that causes significant economic losses to the
swine industry. The lapinized C-strain, a widely used vaccine strain against
CSFV, has low growth efficiency in cell culture, which limits the productivity in
the vaccine industry. In this study, a recombinant virus derived from C-strain
was constructed and subjected to continuous passaging in PK-15 cells with the
goal of acquiring a high progeny virus yield. A cell-adapted virus variant,
RecCpp80, had nearly 1,000-fold higher titer than its parent C-strain but lost
the ability to induce fever in rabbits. Sequence analysis of cell-adapted RecC
variants indicated that at least six nucleotide changes were fixed in RecCpp80.
Further adaption of RecCpp80 variant in swine testicle cells led to a higher
virus yield without additional mutations. Introduction of each of these residues
into the wild-type RecC backbone showed that one mutation, M979R (T3310G),
located in the C-terminal region of E2 might be closely related to the cell
adapted phenotype. Rabbit inoculation revealed that RecCpp80+10 failed to induce
fever in rabbits, whereas RecCpp40+10 caused a fever response similar to the
commercial C-strain vaccine. In conclusion, the C-strain can be adapted to cell
culture by introducing specific mutations in its E2 protein. The mutations in
RecCpp80 that led to the loss of fever response in rabbits require further
investigation. Continuous passaging of the C-strain-based recombinant viruses in
PK-15 cells could enhance its in vitro adaption. The non-synonymous mutations at
3310 and 3531 might play major roles in the enhanced capacity of general virus
reproduction. Such findings may help design a modified C-strain for improved
productivity of commercial vaccines at reduced production cost.
PMID- 28704903
TI - Enchancement of Gamma-Aminobutyric Acid Production by Co-Localization of
Neurospora crassa OR74A Glutamate Decarboxylase with Escherichia coli GABA
Transporter Via Synthetic Scaffold Complex.
AB - Gamma-aminobutyric acid is a precursor of nylon-4, which is a promising heat
resistant biopolymer. GABA can be produced from the decarboxylation of glutamate
by glutamate decarboxylase. In this study, a synthetic scaffold complex strategy
was employed involving the Neurospora crassa glutamate decarboxylase (GadB) and
Escherichia coli GABA antiporter (GadC) to improve GABA production. To construct
the complex, the SH3 domain was attached to the N. crassa GadB, and the SH3
ligand was attached to the N-terminus, middle, and C-terminus of E. coli GadC. In
the C-terminus model, 5.8 g/l of GABA concentration was obtained from 10 g/l
glutamate. When a competing pathway engineered strain was used, the final GABA
concentration was further increased to 5.94 g/l, which corresponds to 97.5% of
GABA yield. With the introduction of the scaffold complex, the GABA productivity
increased by 2.9 folds during the initial culture period.
PMID- 28704904
TI - Development of a Spirulina Extract/Alginate-Imbedded PCL Nanofibrous Cosmetic
Patch.
AB - Cosmetic patches have recently been developed as skin products for personal care
owing to rapid advances in the technology of delivery of active ingredients,
moisture, and adhesiveness to skin. Alginate and Spirulina are typical marine
resources used in cosmetic products. This research involved the development of a
Spirulina extract-impregnated alginate nanofiber cosmetic patch supported by a
polycaprolactone (PCL) nanofiber cover (Spi/Alg-PCL NF patch). In addition to the
ability of alginate to affect moisture and adhesiveness to skin, the impregnation
of Spirulina extract strengthened those abilities as well as its own bioactive
effectiveness. All fabrication processing steps were undertaken in aqueous
solution. The three components (alginate, Spirulina extract, and PCL) had no
detected cytotoxicity in human keratinocyte cell-based examination. In addition,
wetting the pre-dried patch on the skin resulted in the Spirulina extract being
released within 30 min. The results indicate the excellence of the Spi/Alg-PCL NF
patch as a skin-care cosmetic device.
PMID- 28704905
TI - Pyogenic Vertebral Osteomyelitis: Clinical Features, Diagnosis, and Treatment.
AB - Pyogenic vertebral osteomyelitis (PVO) may result in neurological deficits and
sequelae, so early diagnosis and appropriate treatment are critical. Many
previous studies on PVO exist, but our paper has aimed to comprehensively
summarize the clinical aspects of PVO. Through review of the vast literature on
the clinical research of PVO an overview of the clinical characteristics,
diagnostic methods, treatment and prognosis is provided.
PMID- 28704906
TI - The Therapeutic Effects of Combination Therapy with Curcumin and Alendronate on
Spine Fusion Surgery in the Ovariectomized Rats.
AB - OBJECTIVE: The purpose of this study was to evaluate the therapeutic effects of
combination therapy with curcumin and alendronate on spine fusion surgery in
ovariectomized rats. METHODS: Thirty-two female Sprague-Dawley rats (12 weeks
old) underwent bilateral ovariectomy (OVX). Eight weeks after surgery, animals
underwent intertransverse spine fusion at L4-5. The rats were randomly
distributed amongst 4 groups; untreated OVX group, curcumin administered group,
alendronate administered group, and the combination therapy group. At 8 weeks
after fusion surgery, the animals were sacrificed and the fusion mass was
assessed by manual palpation, radiographic scan, and micro-computed tomographic
scan. In addition, mechanical strength was determined by a 3-point bending test.
RESULTS: Based on the results of manual palpation testing and 3-dimensional micro
computed tomography scanning, solid bone fusion rate was 50% (4 of 8) in the OVX
group, 75% (6 of 8) in the alendronate-only and curcumin-only group, and 87.5% (7
of 8) in the combination therapy group, respectively. The combination therapy
group had a higher fusion rate compared with the other treatment groups, though
not statistically significantly (p>0.05). And the combination therapy group had a
significant increase in fusion volume at 8 weeks after spine fusion surgery
compared with curcumin-only group (p=0.039). The 3-point bending test showed that
combination therapy group had a significantly greater maximal load value compared
to that of curcumin-only group (p=0.024). CONCLUSION: The present study
demonstrated that additional treatment of curcumin and alendronate after spine
fusion surgery in rat can promote higher fusion volume, and improve bone
mechanical strength.
PMID- 28704907
TI - Effect of Modic Changes in Cervical Degenerative Disease.
AB - OBJECTIVE: Modic changes are signal intensity changes in adjacent vertebral bone
marrow on magnetic resonance imaging. Few studies have investigated these changes
with regard to the cervical spine. In this study, we investigated the
associations between cervical degenerative disease and Modic changes. METHODS: We
conducted a retrospective collection of radiological data in patients with neck
pain at Pusan National University Yangsan Hospital from January 2010 to December
2014. A total of 169 patients were included in this study. Disc herniation grade,
disc space height and global cervical lordosis (C2-C7 Cobb angle) were measured
and analyzed. If Modic changes were present, we recorded the Modic change type
based on the literature, vertebral level, age, sex, and surgical requirement.
RESULTS: Sixty-six patients exhibited Modic changes in the cervical spine. Out of
these 66 patients, Modic change type II (56 patients, 84.8%) and C5-6 vertebral
level (23 patients, 34.8%) were the most predominant categories. Patients with
Modic change showed worse outcomes in regard to disc herniation grade, disc space
height and global cervical lordosis than patients without (p<0.01). Among 169
patients, 18 patients had undergone anterior cervical discectomy with fusion
(ACDF). Patients with Modic changes (10 of 66 patients, 15.1%) had a greater
probability of undergoing ACDF than those without (8 of 103 patients, 7.8%;
p<0.01). CONCLUSION: Modic changes refer cervical degenerative changes, and
incidence of ACDF is higher when the Modic changes are occurred.
PMID- 28704908
TI - Clinical Results of Odontoid Fractures according to a Modified, Treatment
Oriented Classification.
AB - OBJECTIVE: Odontoid fracture is common in cervical injury, representing about 20%
of total cervical fractures. Classic odontoid fracture classification focused on
anatomy of fracture site has no treatment recommendation and a modified treatment
oriented classification of odontoid fracture was suggested in 2005. We reviewed
our odontoid fracture patients to assess the feasibility and efficacy of Grauer's
classification. METHODS: Between October 2000 and September 2015, we collected
data from patients who came to our institute for odontoid fracture. Demographic
data of patients was reviewed, and neck visual analog scale (VAS) score and
fusion rate were assessed by reviewing electronic medical records
retrospectively. RESULTS: Sixty-nine patients out of a total of eighty two
odontoid fracture patients were reviewed according to Grauer's classification.
Neck VAS of all subtypes in odontoid fracture classification were decreased at
last follow-up (p=0.001). Overall fusion rate was 88.4% at last follow-up.
Concordance rate between Grauer's recommendation and our treatment was 69.9%,
especially in type II with the concordance higher than 80%. Complication was
minimal representing 7.2%, only in types I and III. CONCLUSION: In this study,
there were statistically significant improvement in all subtypes in terms of neck
VAS at the last follow up, especially in types II and III. Grauer's
classification appears to be meaningful to decide treatment plan for odontoid
fractures, especially type II odontoid fracture.
PMID- 28704909
TI - Tophaceous Gout in the Lumbar Spinal Canal Mimicking Epidural Spinal Tumor.
AB - Gout is an inflammatory arthritis characterized by deposition of monosodium urate
crystals in joints. Though gout frequently involves the big toe or other
extremities, it rarely occurs in the spinal canal. A 35-year-old man presented
with left L5 radiculopathy. He had leg pain for 8 months and received several
epidural steroid injections. Magnetic resonance imaging revealed a 1.7*1.1-cm
ovoid contrast-enhancing mass, causing pressure erosion of the left L5 pedicle.
Microscopic laminotomy was performed at the left L5 lamina. White chalky
materials, identified at the left lateral recess of the spinal canal, were
removed in a piecemeal manner. The histopathologic diagnosis was tophaceous gout.
Although the patient's radiating pain did not resolve postoperatively, it was
dramatically relieved with uric acid-lowering medications. If a mass effect is
suspected, surgical removal of gouty tophi might aid in symptom release and
definite diagnosis. Medical treatment after rheumatology consultation is crucial.
PMID- 28704910
TI - Late-Developing Metastatic Malignant Melanoma in the Thoracic Spine Originating
from Choroidal Melanoma.
AB - A 54-year-old woman visited Gangnam Severance Hospital for left side flank pain.
She had a history of total removal of malignant melanoma on the left eye ball 20
years prior. No evaluation had been performed since then. A paravertebral mass at
thoracic ninth level (T9) was discovered on spinal magnetic resonance imaging,
and pathology confirmed malignant melanoma. Following positron emission
tomography-computed tomography, no other metastasis was discovered. After removal
of the paravertebral mass, palliative chemotherapy (dacabarzine + tamoxifene) was
administered in 3 cycles over 2 months. Radiotherapy with simultaneous integrated
boost technique was performed at 4,350 cGy total over 15 days, 290 cGy per
delivery, and was administered with the first cycle of palliative chemotherapy.
Despite this treatment, multiple metastases developed throughout her body 7
months later, and the patient is continuing chemotherapy.
PMID- 28704911
TI - Intradural Extramedullary Capillary Hemangioma In the Upper Thoracic Spine with
Simultaneous Extensive Arachnoiditis.
AB - Capillary hemangiomas are common benign vascular tumors on skin and soft tissues,
but developing as an intradural and extramedullary (IDEM) tumor in spine is
extremely rare. In this report, we present IDEM tumor compressing thoracic cord
in T2-3 level with extensive arachnoiditis below the tumor level in a 60-year-old
man. The lesion was removed and histological diagnosis was capillary hemangioma.
Prompt diagnosis and resection are important to avoid neurological deterioration
from acute hemorrhagic condition. Simultaneous arachnoiditis may be originated
from old subarachnoid hemorrhage associated tumor before diagnosis, and we
suggest it as a helpful diagnostic feature to suspect vascular tumors such as
capillary hemangioma.
PMID- 28704912
TI - Quantitative hepatitis B surface antigen predicts the antiviral response and
hepatocellular carcinoma development in patients with chronic hepatitis B.
PMID- 28704913
TI - Treatment of connective tissue disease-associated interstitial lung disease: the
pulmonologist's point of view.
AB - Interstitial lung disease (ILD) occurs in 15% of patients with collagen vascular
disease (CVD), referred to as connective tissue disease (CTD). Despite advances
in management strategies, ILD continues to be a significant cause of mortality in
patients with CVD-associated ILD (CTD-ILD). There is a lack of randomized,
clinical trials assessing pharmacological agents for CTD-ILD, except in cases of
ILD-associated systemic sclerosis (SSc). This may be due to the lack of CTD cases
available, the difficulty of histological confirmation of ILD, and the various
types of CTD and ILD. As a result, evidence-based pharmacological treatment of
CTD-ILD is not yet well established. CTD-ILD presents with varying degrees of
histology, from inflammation to fibrosis, and a wide spectrum of clinical
manifestations, from minimal symptoms to respiratory failure. This renders it
difficult for clinicians to make decisions regarding treatment options,
observational strategies, optimal timing for interventions, and the
appropriateness of pharmacological agents for treatment. There is no specific
treatment for reversing fibrosis-like idiopathic pulmonary fibrosis in a clinical
setting. This review describes pharmacological interventions for SSc-ILD
described in randomized control trials, and presents an overview of recent
advances of CTD-ILD-dependent treatments based on the types of CTD.
PMID- 28704914
TI - Impact of early diagnosis on functional preservation in patients with rheumatoid
arthritis: the early bird catches the worm.
PMID- 28704915
TI - Treatment of diabetic kidney disease: current and future targets.
AB - Diabetic kidney disease (DKD) is a leading cause of end-stage renal disease in
Korea and worldwide, and is a risk factor for the development of cardiovascular
complications. The conventional treatments for DKD are control of blood glucose
and blood pressure levels by inhibiting the renin-angiotensin system. However,
the prevalence of DKD continues to increase and additional therapies are required
to prevent or ameliorate the condition. Many drugs have been, or are being,
developed to target the molecular mechanisms in play in DKD. This review focuses
on DVD treatment, considering current and emerging therapeutic targets and the
clinical trial-based evidence.
PMID- 28704916
TI - Three-dimensional echocardiography in adult congenital heart disease.
AB - Congenital heart disease (CHD) is now more common in adults than in children due
to improvements in fetal echo, neonatal and pediatric care, and surgical
techniques leading to dramatically increased survivability into adulthood. Adult
patients with CHD, regardless of prior cardiac surgery, experience further
cardiac problems or therapeutic challenges; therefore, a non-invasive, easily
accessible echocardiographic examination is an essential follow-up tool. Among
echocardiographic modalities, three-dimensional (3D) echocardiography provides
better delineation of spatial relationships in complex cardiac geometries and
more accurate volumetric information without geometric assumptions. For atrial
septal defects, an en face view of the tissue defect allows better decisions on
device closure. For tricuspid valve malformations, an en face view provides
diagnostic information that is difficult to obtain from routine 2D tomography. In
repaired tetralogy of fallot with pulmonary regurgitation, preoperative 3D
echocardiography- based right ventricular volume may be used to determine the
timing of a pulmonary valve replacement in conjunction with cardiovascular
magnetic imaging. For optimal adult CHD care, 3D echocardiography is an important
complement to routine 2D echocardiography.
PMID- 28704917
TI - The role of hypoxia on the acquisition of epithelial-mesenchymal transition and
cancer stemness: a possible link to epigenetic regulation.
AB - A hypoxic microenvironment leads to cancer progression and increases the
metastatic potential of cancer cells within tumors via epithelial-mesenchymal
transition (EMT) and cancer stemness acquisition. The hypoxic response pathway
can occur under oxygen tensions of < 40 mmHg through hypoxia-inducible factors
(HIFs), which are considered key mediators in the adaptation to hypoxia. Previous
studies have shown that cellular responses to hypoxia are required for EMT and
cancer stemness maintenance through HIF-1alpha and HIF-2alpha. The principal
transcription factors of EMT include Twist, Snail, Slug, Sip1 (Smad interacting
protein 1), and ZEB1 (zinc finger E-box-binding homeobox 1). HIFs bind to hypoxia
response elements within the promoter region of these genes and also target
cancer stem cell-associated genes and mediate transcriptional responses to
hypoxia during stem cell differentiation. Acquisition of stemness characteristics
in epithelial cells can be induced by activation of the EMT process. The
mechanism of these phenotypic changes includes epigenetic alterations, such as
DNA methylation, histone modification, chromatin remodeling, and microRNAs.
Increased expression of EMT and pluripotent genes also play a role through
demethylation of their promoters. In this review, we summarize the role of
hypoxia on the acquisition of EMT and cancer stemness and the possible
association with epigenetic regulation, as well as their therapeutic
applications.
PMID- 28704918
TI - Anticancer activity of graphene oxide-reduced graphene oxide-silver nanoparticle
composites.
AB - In the present study, a chemical route was employed to synthesize graphene oxide
(GO)-reduced graphene oxide (rGO)-Ag nanoparticle (AgNP) composites from graphite
and AgNO3 using vitamin C as reducing agent. Powder X-ray diffraction pattern and
field emission scanning electron microscope images revealed that the AgNP were
uniformly distributed on the surface of GO and rGO nanosheets. For the first
time, the cytotoxicity of GO, rGO, AgNP, GO-AgNP and rGO-AgNP composites were
examined against human lung cancer A549 cells using MTT assay and reported
quantitatively. The rGO-AgNP showed significant cytotoxicity activity with an
IC50 value of 30MUg/mL towards A549 cells which is higher than that of GO
(180MUg/mL), rGO (160MUg/mL) and GO-AgNP (100MUg/mL). Compared to AgNP (6MUg/mL),
rGO-AgNP shows partial agglomeration of AgNP on rGO sheets, which reduces the
interaction between rGO-AgNP and A549 cells leading to lesser anticancer activity
than AgNP. The interaction between rGO and AgNP leads to increase in the material
biocompatibility, reducing the toxicity and corrosive characteristic.
PMID- 28704919
TI - The Role of Radiation Induced Injury on Lung Cancer.
AB - This manuscript evaluates the role of cell killing, tissue disorganization, and
tissue damage on the induction of lung cancer following low dose rate radiation
exposures from internally deposited radioactive materials. Beagle dogs were
exposed by inhalation to 90Y, 91Y, 144Ce, or 90Sr in fused clay particles. Dogs
lived out their life span with complete pathology conducted at the time of death.
The radiation dose per cell turnover was characterized and related to the cause
of death for each animal. Large doses per cell turnover resulted in acute death
from lung damage with extensive cell killing, tissue disorganization, chronic
inflammatory disease, fibrosis, and pneumonitis. Dogs with lower doses per cell
turnover developed a very high frequency of lung cancer. As the dose per cell
turnover was further decreased, no marked tissue damage and no significant change
in either life span or lung cancer frequency was observed. Radiation induced
tissue damage and chronic inflammatory disease results in high cancer frequencies
in the lung. At doses where a high frequency of chromosome damage and mutations
would be predicted to occur there was no decrease in life span or increase in
lung cancer. Such research suggests that cell killing and tissue damage and the
physiological responses to that damage are important mechanisms in radiation
induced lung cancer.
PMID- 28704920
TI - A Synergy Cropland of China by Fusing Multiple Existing Maps and Statistics.
AB - Accurate information on cropland extent is critical for scientific research and
resource management. Several cropland products from remotely sensed datasets are
available. Nevertheless, significant inconsistency exists among these products
and the cropland areas estimated from these products differ considerably from
statistics. In this study, we propose a hierarchical optimization synergy
approach (HOSA) to develop a hybrid cropland map of China, circa 2010, by fusing
five existing cropland products, i.e., GlobeLand30, Climate Change Initiative
Land Cover (CCI-LC), GlobCover 2009, MODIS Collection 5 (MODIS C5), and MODIS
Cropland, and sub-national statistics of cropland area. HOSA simplifies the
widely used method of score assignment into two steps, including determination of
optimal agreement level and identification of the best product combination. The
accuracy assessment indicates that the synergy map has higher accuracy of spatial
locations and better consistency with statistics than the five existing datasets
individually. This suggests that the synergy approach can improve the accuracy of
cropland mapping and enhance consistency with statistics.
PMID- 28704921
TI - EYS Mutations Causing Autosomal Recessive Retinitis Pigmentosa: Changes of
Retinal Structure and Function with Disease Progression.
AB - Mutations in the EYS (eyes shut homolog) gene are a common cause of autosomal
recessive (ar) retinitis pigmentosa (RP). Without a mammalian model of human EYS
disease, there is limited understanding of details of disease expression and
rates of progression of the retinal degeneration. We studied clinically and with
chromatic static perimetry, spectral-domain optical coherence tomography (OCT),
and en face autofluoresence imaging, a cohort of 15 patients (ages 12-51 at first
visit), some of whom had longitudinal data of function and structure. Rod
sensitivity was able to be measured by chromatic perimetry in most patients at
their earliest visits and some patients retained patchy rod function into the
fifth decade of life. As expected from RP, cone sensitivity persisted after rod
function was no longer measurable. The photoreceptor nuclear layer of the central
retina was abnormal except at the fovea in most patients at first visit.
Perifoveal disease measured over a period of years indicated that photoreceptor
structural loss was followed by dysmorphology of the inner retina and loss of
retinal pigment epithelial integrity. Although there could be variability in
severity, preliminary analyses of the rates of vision loss suggested that EYS is
a more rapidly progressive disease than other ciliopathies causing arRP, such as
USH2A and MAK.
PMID- 28704922
TI - Transcriptome Differences in Porcine Alveolar Macrophages from Tongcheng and
Large White Pigs in Response to Highly Pathogenic Porcine Reproductive and
Respiratory Syndrome Virus (PRRSV) Infection.
AB - Porcine reproductive and respiratory syndrome virus (PRRSV) is a single-stranded
positive-sense RNA virus that can cause devastating reproductive failure and
respiratory tract lesions, which has led to serious damage to the swine industry
worldwide. Our previous studies have indicated that Tongcheng (TC) pigs, a
Chinese local breed, have stronger resistance or tolerance to PRRSV infection
than Large White (LW) pigs. This study aims to investigate their host
transcriptome differences in porcine alveolar macrophages (PAMs) at 7 days post
challenge. Transcriptome profiling of PAMs from PRRSV infected and control pigs
of these two breeds were performed using RNA-sequencing. For both breeds, there
were 1257 common differentially expressed genes (DEGs) in response to PRRSV
infection, involving hepatic fibrosis/hepatic stellate cell activation,
phospholipase C, and granulocyte adhesion and diapedesis pathways. For TC pig,
549 specific DEGs were identified, including VAV2, BCL2 and BAX, which were
enriched in activation of leukocyte extravasation and suppression of apoptosis.
While, 898 specific DEGs were identified in LW pigs, including GNAQ, GNB5, GNG2,
CALM4 and RHOQ, which were involved in suppression of Galphaq and PI3K-AKT
signaling. This study provides an insight into the transcriptomic comparison of
resistant and susceptible pigs to PRRSV infection. TC pigs may promote the
extravasation and migration of leukocytes to defend against PRRSV infections and
suppress apoptosis of the infected macrophages to increase antigen presentation,
thereby reducing the lung lesions.
PMID- 28704923
TI - Production of Cow's Milk Free from Beta-Casein A1 and Its Application in the
Manufacturing of Specialized Foods for Early Infant Nutrition.
AB - Beta-casein (BC) is frequently expressed as BC A2 and BC A1 in cow's milk.
Gastrointestinal digestion of BC A1 results in the release of the opioid peptide
beta-casomorphin 7 (BCM7) which is less likely to occur from BC A2. This work was
aimed to produce milk containing BC A2 with no BC A1 (BC A2 milk) using
genetically selected CSN2 A2A2 Jersey cows. Additionally, we aimed to develop an
infant formula (IF) suitable for healthy full-term infants during the first six
months of life based on BC A2 milk. The concentration of BCM7 released from BC A2
IF, from commercially available IFs as well as from human milk and raw cow's milk
was evaluated after simulated gastrointestinal digestion (SGID). BC A2 IF
presented the lowest mean relative abundance of BC A1 (IF 1 = 0.136 +/- 0.010),
compared with three commercially available IFs (IF 2 = 0.597 +/- 0.020; IF 3 =
0.441 +/- 0.014; IF 4 = 0.503 +/- 0.011). Accordingly, SGID of whole casein
fraction from BC A2 IF resulted in a significantly lower release of BCM7 (IF 1 =
0.860 +/- 0.014 ug/100 mL) compared to commercially available IFs (IF 2 = 2.625
+/- 0.042 ug/100 mL; IF 3 = 1.693 +/- 0.012 ug/100 mL; IF 4 = 1.962 +/- 0.067
ug/100 mL). Nevertheless, BCM7 levels from BC A2 IF were significantly higher
than those found in SGID hydrolysates of BC A2 raw milk (0.742 +/- 0.008 ug/100
mL). Interestingly, results showed that BCM7 was also present in human milk in
significantly lower amounts (0.697 +/- 0.007 ug/100 mL) than those observed in IF
1 and BC A2 milk. This work demonstrates that using BC A2 milk in IF formulation
significantly reduces BCM7 formation during SGID. Clinical implications of BC A2
IF on early infant health and development need further investigations.
PMID- 28704924
TI - lncRNAs and MYC: An Intricate Relationship.
AB - Long non-coding RNAs (lncRNAs) are emerging as important regulators of gene
expression networks, acting either at the transcriptional level, by influencing
histone modifications, or at the post-transcriptional level, by controlling mRNA
stability and translation. Among the gene expression networks known to influence
the process of oncogenic transformation, the one controlled by the proto-oncogene
MYC is one of the most frequently deregulated in cancer. In B-cell lymphomas, the
MYC gene is subject to chromosomal rearrangements that result in MYC
overexpression. In many other cancers, the region surrounding MYC is subject to
gene amplification. MYC expression is also controlled at the level of protein and
mRNA stability. Neoplastic lesions affecting MYC expression are responsible for a
drastic change in the number and the type of genes that are transcriptionally
controlled by MYC, depending on differential promoter affinities. Transcriptome
profiling of tumor samples has shown that several lncRNAs can be found
differentially regulated by MYC in different cancer types and many of them can
influence cancer cell viability and proliferation. At the same time, lncRNAs have
been shown to be able to control the expression of MYC itself, both at
transcriptional and post-transcriptional levels. Given that targeting the MYC
dependent transcriptional program has the potential to reach broad anticancer
activity, molecular dissection of the complex regulatory mechanisms governing MYC
expression will be crucial in the future for the identification of novel
therapeutic strategies.
PMID- 28704925
TI - Licochalcone A Prevents Platelet Activation and Thrombus Formation through the
Inhibition of PLCgamma2-PKC, Akt, and MAPK Pathways.
AB - Platelet activation is involved in cardiovascular diseases, such as
atherosclerosis and ischemic stroke. Licochalcone A (LA), an active ingredient of
licorice, exhibits multiple biological activities such as anti-oxidation and anti
inflammation. However, its role in platelet activation remains unclear.
Therefore, the study investigated the antiplatelet mechanism of LA. Our data
revealed that LA (2-10 MUM) concentration dependently inhibited platelet
aggregation induced by collagen, but not thrombin and U46619. LA markedly
attenuated collagen-stimulated ATP release, P-selectin secretion, calcium
mobilization, and GPIIbIIIa activation, but did not interfere with the collagen
binding to platelets. Moreover, LA significantly reduced the activation of
PLCgamma2, PKC, Akt and MAPKs. Thus, LA attenuates platelet activation, possibly
by inhibiting collagen receptor downstream signaling but not by blocking the
collagen receptors. In addition, LA prevented adenosine diphosphate (ADP)-induced
acute pulmonary thrombosis, fluorescein sodium-induced platelet thrombus
formation, and middle cerebral artery occlusion/reperfusion-induced brain injury
in mice, but did not affect normal hemostasis. This study demonstrated that LA
effectively reduced platelet activation and thrombus formation, in part, through
the inhibition of PLCgamma2-PKC, Akt, and MAPK pathways, without the side effect
of bleeding. These findings also indicate that LA may provide a safe and
alternative therapeutic approach for preventing thromboembolic disorders such as
stroke.
PMID- 28704926
TI - A Label-Free and Ultrasensitive Immunosensor for Detection of Human Chorionic
Gonadotrophin Based on Graphene FETs.
AB - We report on a label-free immunosensor based on graphene field effect transistors
(G-FETs) for the ultrasensitive detection of Human Chorionic Gonadotrophin (hCG),
as an indicator of pregnancy and related disorders, such as actopic pregnancy,
choriocarcinoma and orchic teratoma. Pyrene based bioactive ester was non
covalently anchored onto the graphene channel in order to retain the sp2 lattice.
The G-FET transfer characteristics showed repeatable and reliable responses in
all surface modifying steps using a direct current (DC) readout system. The hCG
concentration gradient showed a detection limit of ~1 pg.mL-1. The proposed
method facilitates the cost-effective and viable production of graphene point-of
care devices for clinical diagnosis.
PMID- 28704927
TI - The TOR Signaling Network in the Model Unicellular Green Alga Chlamydomonas
reinhardtii.
AB - Cell growth is tightly coupled to nutrient availability. The target of rapamycin
(TOR) kinase transmits nutritional and environmental cues to the cellular growth
machinery. TOR functions in two distinct multiprotein complexes, termed TOR
complex 1 (TORC1) and TOR complex 2 (TORC2). While the structure and functions of
TORC1 are highly conserved in all eukaryotes, including algae and plants, TORC2
core proteins seem to be missing in photosynthetic organisms. TORC1 controls cell
growth by promoting anabolic processes, including protein synthesis and ribosome
biogenesis, and inhibiting catabolic processes such as autophagy. Recent studies
identified rapamycin-sensitive TORC1 signaling regulating cell growth, autophagy,
lipid metabolism, and central metabolic pathways in the model unicellular green
alga Chlamydomonas reinhardtii. The central role that microalgae play in global
biomass production, together with the high biotechnological potential of these
organisms in biofuel production, has drawn attention to the study of proteins
that regulate cell growth such as the TOR kinase. In this review we discuss the
recent progress on TOR signaling in algae.
PMID- 28704929
TI - Radio-Frequency-Based NH3-Selective Catalytic Reduction Catalyst Control: Studies
on Temperature Dependency and Humidity Influences.
AB - The upcoming more stringent automotive emission legislations and current
developments have promoted new technologies for more precise and reliable
catalyst control. For this purpose, radio-frequency-based (RF) catalyst state
determination offers the only approach for directly measuring the NH3 loading on
selective catalytic reduction (SCR) catalysts and the state of other catalysts
and filter systems. Recently, the ability of this technique to directly control
the urea dosing on a current NH3 storing zeolite catalyst has been demonstrated
on an engine dynamometer for the first time and this paper continues that work.
Therefore, a well-known serial-type and zeolite-based SCR catalyst (Cu-SSZ-13)
was investigated under deliberately chosen high space velocities. At first, the
full functionality of the RF system with Cu-SSZ-13 as sample was tested
successfully. By direct RF-based NH3 storage control, the influence of the
storage degree on the catalyst performance, i.e., on NOx conversion and NH3 slip,
was investigated in a temperature range between 250 and 400 degrees C. For each
operation point, an ideal and a critical NH3 storage degree was found and
analyzed in the whole temperature range. Based on the data of all experimental
runs, temperature dependent calibration functions were developed as a basis for
upcoming tests under transient conditions. Additionally, the influence of exhaust
humidity was observed with special focus on cold start water and its effects to
the RF signals.
PMID- 28704928
TI - Dynamic Hippocampal and Prefrontal Contributions to Memory Processes and
Representations Blur the Boundaries of Traditional Cognitive Domains.
AB - The hippocampus has long been known to be a critical component of the memory
system involved in the formation and use of long-term declarative memory.
However, recent findings have revealed that the reach of hippocampal
contributions extends to a variety of domains and tasks that require the flexible
use of cognitive and social behavior, including domains traditionally linked to
prefrontal cortex (PFC), such as decision-making. In addition, the prefrontal
cortex (PFC) has gained traction as a necessary part of the memory system. These
findings challenge the conventional characterizations of hippocampus and PFC as
being circumscribed to traditional cognitive domains. Here, we emphasize that the
ability to parsimoniously account for the breadth of hippocampal and PFC
contributions to behavior, in terms of memory function and beyond, requires
theoretical advances in our understanding of their characteristic processing
features and mental representations. Notably, several literatures exist that
touch upon this issue, but have remained disjointed because of methodological
differences that necessarily limit the scope of inquiry, as well as the somewhat
artificial boundaries that have been historically imposed between domains of
cognition. In particular, this article focuses on the contribution of relational
memory theory as an example of a framework that describes both the
representations and processes supported by the hippocampus, and further
elucidates the role of the hippocampal-PFC network to a variety of behaviors.
PMID- 28704930
TI - Mitochondrial Dysfunction Mediated by Poly(ADP-Ribose) Polymerase-1 Activation
Contributes to Hippocampal Neuronal Damage Following Status Epilepticus.
AB - Mitochondrial dysfunction plays a central role in the neuropathology associated
with status epilepticus (SE) and is implicated in the development of epilepsy.
While excitotoxic mechanisms are well-known mediators affecting mitochondrial
health following SE, whether hyperactivation of poly(ADP-ribose) polymerase-1
(PARP-1) also contributes to SE-induced mitochondrial dysfunction remains to be
examined. Here we first evaluated the temporal evolution of poly-ADP-ribosylated
protein levels in hippocampus following kainic acid-induced SE as a marker for
PARP-1 activity, and found that PARP-1 was hyperactive at 24 h following SE. We
evaluated oxidative metabolism and found decreased NAD+ levels by enzymatic
cycling, and impaired NAD+-dependent mitochondrial respiration as measured by
polarography at 24 h following SE. Stereological estimation showed significant
cell loss in the hippocampal CA1 and CA3 subregions 72 h following SE. PARP-1
inhibition using N-(6-Oxo-5,6-dihydro-phenanthridin-2-yl)- N,N-dimethylacetamide
(PJ-34) in vivo administration was associated with preserved NAD+ levels and NAD+
dependent mitochondrial respiration, and improved CA1 neuronal survival. These
findings suggest that PARP-1 hyperactivation contributes to SE-associated
mitochondrial dysfunction and CA1 hippocampal damage. The deleterious effects of
PARP-1 hyperactivation on mitochondrial respiration are in part mediated through
intracellular NAD+ depletion. Therefore, modulating PARP-1 activity may represent
a potential therapeutic target to preserve intracellular energetics and
mitochondrial function following SE.
PMID- 28704931
TI - Alterations in Circulating Amino Acid Metabolite Ratio Associated with Arginase
Activity Are Potential Indicators of Metabolic Syndrome: The Korean Genome and
Epidemiology Study.
AB - Upregulated arginase activity, which competes with nitric oxide synthase (NOS),
impairs nitric oxide production and has been implicated in various metabolic
disorders. This study examined whether circulating amino acid metabolite ratios
are associated with arginase and NOS activities and whether arginine
bioavailability is associated with metabolic syndrome (MetS). Data related to
arginase and NOS activities were collected from non-diabetic Koreans without
cardiovascular disease (n = 1998) in the Ansan-Ansung cohorts (2005-2006).
Subsequently, correlation and multivariate logistic regression analyses were
performed. With the increase in the number of MetS risk factors, ratios of
circulating amino acid metabolites, such as those of ornithine/citrulline,
proline/citrulline, and ornithine/arginine, also significantly increased, whereas
arginine bioavailability significantly decreased. These metabolite ratios and
arginase bioavailability were also significantly correlated with MetS risk
related parameters, which remained significant after adjusting for covariates. In
addition, logistic regression analysis revealed that high ratios of circulating
metabolites and low arginine bioavailability, which indicated increased arginase
activity, were significantly associated with a high MetS risk. This study
demonstrated that altered ratios of circulating amino acid metabolites indicates
increased arginase activity and decreased arginine bioavailability, both of which
can be potential markers for MetS risk.
PMID- 28704932
TI - Sodium Reduction in Processed Foods in Brazil: Analysis of Food Categories and
Voluntary Targets from 2011 to 2017.
AB - Non-communicable diseases, including cardiovascular diseases, are responsible for
over 70% of deaths in Brazil. Currently, over 25% of Brazilian adults are
diagnosed as hypertensive; overall, current dietary sodium intake in Brazil (4700
mg/person) is over twice the international recommendations, and 70-90% of
adolescents and adults consume excessive sodium. National sodium reduction
strategies consider the main dietary sources of sodium to be added salt to foods,
foods consumed outside of the household, and sodium in processed foods. The
national voluntary strategy for sodium reduction in priority food categories has
been continuously monitored over a 6-year period (2011-2017) and there was a
significant 8-34% reduction in the average sodium content of over half food
categories. Different food categories have undergone differing reductions in
sodium over time, aiding gradual biannual targets to allow industries to develop
new technologies and consumers to adapt to foods with less salt. By 2017, most
products of all food categories had met the regional targets proposed by the Pan
American Health Organization, showing that voluntary sodium reduction strategies
can potentially contribute to food reformulation. Nevertheless, regulatory
approaches may still be necessary in the future in order to reach all food
producers and to allow stronger enforcement to meet more stringent regional
targets.
PMID- 28704933
TI - Functional Hybrid Materials Based on Manganese Dioxide and Lignin Activated by
Ionic Liquids and Their Application in the Production of Lithium Ion Batteries.
AB - Kraft lignin (KL) was activated using selected ionic liquids (ILs). The activated
form of the biopolymer, due to the presence of carbonyl groups, can be used in
electrochemical tests. To increase the application potential of the system in
electrochemistry, activated lignin forms were combined with manganese dioxide,
and the most important physicochemical and morphological-microstructural
properties of the novel, functional hybrid systems were determined using Fourier
transform infrared spectroscopy (FTIR), elemental analysis (EA), scanning
electron microscopy (SEM), zeta potential analysis, thermal stability (TGA/DTG)
and porous structure analysis. An investigation was also made of the practical
application of the hybrid materials in the production of lithium ion batteries.
The capacity of the anode (MnO2/activated lignin), working at a low current
regime of 50 mA.g-1, was ca. 610 mAh.g-1, while a current of 1000 mA.g-1 resulted
in a capacity of 570 mAh.g-1. Superior cyclic stability and rate capability
indicate that this may be a promising electrode material for use in high
performance lithium ion batteries.
PMID- 28704934
TI - Functioning of Fluorescent Proteins in Aggregates in Anthozoa Species and in
Recombinant Artificial Models.
AB - Despite great advances in practical applications of fluorescent proteins (FPs),
their natural function is poorly understood. FPs display complex spatio-temporal
expression patterns in living Anthozoa coral polyps. Here we applied confocal
microscopy, specifically, the fluorescence recovery after photobleaching (FRAP)
technique to analyze intracellular localization and mobility of endogenous FPs in
live tissues. We observed three distinct types of protein distributions in living
tissues. One type of distribution, characteristic for Anemonia, Discosoma and
Zoanthus, is free, highly mobile cytoplasmic localization. Another pattern is
seen in FPs localized to numerous intracellular vesicles, observed in Clavularia.
The third most intriguing type of intracellular localization is with respect to
the spindle-shaped aggregates and lozenge crystals several micrometers in size
observed in Zoanthus samples. No protein mobility within those structures was
detected by FRAP. This finding encouraged us to develop artificial aggregating
FPs. We constructed "trio-FPs" consisting of three tandem copies of tetrameric
FPs and demonstrated that they form multiple bright foci upon expression in
mammalian cells. High brightness of the aggregates is advantageous for early
detection of weak promoter activities. Simultaneously, larger aggregates can
induce significant cytostatic and cytotoxic effects and thus such tags are not
suitable for long-term and high-level expression.
PMID- 28704935
TI - Entrainment of Breast Cell Lines Results in Rhythmic Fluctuations of MicroRNAs.
AB - Circadian rhythms are essential for temporal (~24 h) regulation of molecular
processes in diverse species. Dysregulation of circadian gene expression has been
implicated in the pathogenesis of various disorders, including hypertension,
diabetes, depression, and cancer. Recently, microRNAs (miRNAs) have been
identified as critical modulators of gene expression post-transcriptionally, and
perhaps involved in circadian clock architecture or their output functions. The
aim of the present study is to explore the temporal expression of miRNAs among
entrained breast cell lines. For this purpose, we evaluated the temporal (28 h)
expression of 2006 miRNAs in MCF-10A, MCF-7, and MDA-MB-231 cells using
microarrays after serum shock entrainment. We noted hundreds of miRNAs that
exhibit rhythmic fluctuations in each breast cell line, and some of them across
two or three cell lines. Afterwards, we validated the rhythmic profiles exhibited
by miR-141-5p, miR-1225-5p, miR-17-5p, miR-222-5p, miR-769-3p, and miR-548ay-3p
in the above cell lines, as well as in ZR-7530 and HCC-1954 using RT-qPCR. Our
results show that serum shock entrainment in breast cells lines induces rhythmic
fluctuations of distinct sets of miRNAs, which have the potential to be related
to endogenous circadian clock, but extensive investigation is required to
elucidate that connection.
PMID- 28704936
TI - Effects of a New Nutraceutical Formulation (Berberine, Red Yeast Rice and
Chitosan) on Non-HDL Cholesterol Levels in Individuals with Dyslipidemia: Results
from a Randomized, Double Blind, Placebo-Controlled Study.
AB - Increased non high-density lipoprotein (HDL)/low-density lipoprotein (LDL)
cholesterol levels are independent risk factors for cardiovascular (CV) mortality
with no documented threshold. A new combination of nutraceuticals (berberine 200
mg, monacolin K 3 mg, chitosan 10 mg and coenzyme Q 10 mg) with additive lipid
lowering properties has become available. The aim of the study is to test the
efficacy of the nutraceutical formulation (one daily) in lowering non-HDL
cholesterol vs. placebo at 12 weeks in individuals with non-HDL-cholesterol
levels >=160 mg/dL. 39 subjects (age 52 +/- 11 years; 54% females; body mass
index 27 +/- 4 kg/m2) were randomized (3:1) in a double blind phase II placebo
controlled study. At baseline, 4 and 12 weeks main clinical/biohumoral
parameters, pro-inflammatory cytokines, (gut)-hormones, proprotein convertase
subtilisin/kexin type 9 (PCSK9) levels and endothelial progenitor cell (EPC)
number were assessed. Baseline characteristics were comparable in the two groups.
The intervention significantly decreased non-HDL cholesterol (-30 +/- 20 mg/dL; p
= 0.012), LDL cholesterol (-31 +/- 18 mg/dL, p = 0.011) and apolipoprotein (Apo)
B (-14 +/- 12 mg/dL, p = 0.030) levels compared to the placebo. Pro-inflammatory,
hormonal, PCSK9 and EPC levels remained stable throughout the study in both
groups. The intervention was well tolerated. Three adverse events occurred:
Epstein Barr virus infection, duodenitis and asymptomatic but significant
increase in creatine phosphokinase (following intense physical exercise) which
required hospitalization. The tested nutraceutical formulation may represent a
possible therapeutic strategy in dyslipidemic individuals in primary prevention.
PMID- 28704937
TI - Attenuation of Red Blood Cell Storage Lesions with Vitamin C.
AB - : Stored red blood cells (RBCs) undergo oxidative stress that induces deleterious
metabolic, structural, biochemical, and molecular changes collectively referred
to as "storage lesions". We hypothesized that vitamin C (VitC, reduced or
oxidized) would reduce red cell storage lesions, thus prolonging their storage
duration. Whole-blood-derived, leuko-reduced, SAGM (saline-adenine-glucose
mannitol)-preserved RBC concentrates were equally divided into four pediatric
storage bags and the following additions made: (1) saline (saline); (2) 0.3
mmol/L reduced VitC (Lo VitC); (3) 3 mmol/L reduced VitC (Hi VitC); or (4) 0.3
mmol/L oxidized VitC (dehydroascorbic acid, DHA) as final concentrations.
Biochemical and rheological parameters were serially assessed at baseline (prior
to supplementation) and Days 7, 21, 42, and 56 for RBC VitC concentration, pH,
osmotic fragility by mechanical fragility index, and percent hemolysis, LDH
release, glutathione depletion, RBC membrane integrity by scanning electron
microscopy, and Western blot for beta-spectrin. VitC exposure (reduced and
oxidized) significantly increased RBC antioxidant status with varying dynamics
and produced trends in reduction in osmotic fragility and increases in membrane
integrity. CONCLUSION: VitC partially protects RBC from oxidative changes during
storage. Combining VitC with other antioxidants has the potential to improve long
term storage of RBC.
PMID- 28704939
TI - Response to Comment on Giuseppe Genchi et al. Mercury Exposure and Heart
Diseases. Int. J. Environ. Res. Public Health 2017, 14, 74.
PMID- 28704938
TI - NADPH Oxidases, Angiogenesis, and Peripheral Artery Disease.
AB - Peripheral artery disease (PAD) is caused by narrowing of arteries in the limbs,
normally occurring in the lower extremities, with severe cases resulting in
amputation of the foot or leg. A potential approach for treatment is to stimulate
the formation of new blood vessels to restore blood flow to limb tissues. This is
a process called angiogenesis and involves the proliferation, migration, and
differentiation of endothelial cells. Angiogenesis can be stimulated by reactive
oxygen species (ROS), with NADPH oxidases (NOX) being a major source of ROS in
endothelial cells. This review summarizes the recent evidence implicating NOX
isoforms in their ability to regulate angiogenesis in vascular endothelial cells
in vitro, and in PAD in vivo. Increasing our understanding of the involvement of
the NOX isoforms in promoting therapeutic angiogenesis may lead to new treatment
options to slow or reverse PAD.
PMID- 28704940
TI - Effects of Protein-Iron Complex Concentrate Supplementation on Iron Metabolism,
Oxidative and Immune Status in Preweaning Calves.
AB - The objective of this study was to determine the effects of feeding protein-iron
complex (PIC) on productive performance and indicators of iron metabolism,
hematology parameters, antioxidant and immune status during first 35 days of a
calf's life. Preparation of the complex involved enzymatic hydrolysis of milk
casein (serine protease from Yarrowia lipolytica yeast). Iron chloride was then
added to the hydrolyzate and lyophilizate. Calves were divided into treated
groups: LFe (low iron dose) 10 g/day calf of protein-iron complex, HFe (height
iron dose) 20 g/day calf, and control group. Dietary supplements containing the
lower dose of concentrate had a significant positive effect on iron metabolism,
while the higher dose of concentrate resulted in increase of total iron binding
capacity (TIBC), saturation of transferrin and decrease of and unsaturated iron
binding capacity (UIBC), which suggest iron overload. Additionally, treatment
with the lower dose of iron remarkably increased the antioxidant parameters,
mainly total antioxidant (TAS) and glutathione peroxidase activity (GPx). Higher
doses of PIC were related to lower total antioxidant status. IgG, IgM, insulin,
glucose, TNFalpha and IGF-1 concentration did not change significantly in either
group after supplementation. In practice, the use of protein-iron complex
concentrate requires taking into account the iron content in milk replacers and
other feedstuffs.
PMID- 28704941
TI - Effect of UV-C Radiation, Ultra-Sonication Electromagnetic Field and Microwaves
on Changes in Polyphenolic Compounds in Chokeberry (Aronia melanocarpa).
AB - Chokeberry fruits are highly valued for their high content of polyphenolic
compounds. The use of such abiotic stress factors as UV-C radiation, an
electromagnetic field, microwave radiation, and ultrasound, at different
operation times, caused differentiation in the contents of anthocyanins, phenolic
acids, flavonols, and flavan-3-ols. Samples were analyzed for contents of
polyphenolics with ultra-performance liquid chromatography and photodiode
detector-quadrupole/time-of-flight mass spectrometry (UPLC-PDA-MS/MS). The
analysis showed that after exposure to abiotic stress factors, the concentration
of anthocyanins ranged from 3587 to 6316 mg/100 g dry matter (dm) that
constituted, on average, 67.6% of all identified polyphenolic compounds. The
second investigated group included phenolic acids with the contents ranging
between 1480 and 2444 mg/100 g dm (26.5%); then flavonols within the range of 133
to 243 mg/100 g dm (3.7%), and finally flavan-3-ols fluctuated between 191 and
369 mg/100 g dm (2.2%). The use of abiotic stress factors such as UV-C radiation,
microwaves and ultrasound field, in most cases contributed to an increase in the
content of the particular polyphenolic compounds in black chokeberry. Under the
influence of these factors, increases were observed: in anthocyanin content, of
22%; in phenolic acids, of 20%; in flavonols, of 43%; and in flavan-3-ols, of
30%. Only the use of the electromagnetic field caused a decrease in the content
of the examined polyphenolic compounds.
PMID- 28704942
TI - Specialized Metabolites of the Lichen Vulpicida pinastri Act as Photoprotective
Agents.
AB - The extreme resiliency of lichens to UV radiations makes them an interesting
model to find new photoprotective agents acting as UV-blockers and antioxidant.
In this research, using a new in vitro method designed to overcome the shortage
of material associated to many studies dealing with natural products, we show
that the three major compounds isolated from the lichen Vulpicida pinastri,
vulpinic acid, pinastric acid and usnic acid, were UV blocker agents. Antioxidant
assays evidenced superoxide anion scavenging activity. Combination of the most
promising compounds against UVB and UVB radiations, usnic acid, vulpinic acid and
pinastric acid, increased the photoprotective activity. At the same time, they
were found not cytotoxic on keratinocyte cell lines and photostable in the UVA
and UVB ranges. Thus, lichens represent an attractive source to find good
candidate ingredients as photoprotective agents. Additionally, the uncommon
scalemic usnic acid mixture in this Vulpicida species was proven through
electronic circular dichroism calculation.
PMID- 28704943
TI - Constancy and Change: Key Issues in Housing and Health Research, 1987-2017.
AB - The low impact of scientific research on the relations between housing and health
during the last 30 years can be attributed to a number of reasons. First,
statistical analyses have meant to improve understanding of the relations between
what are interpreted and measured as causal factors. However, any single
statistical approach fails to account for the dynamic non-linear relations
between multiple factors and therefore cannot analyze systemic complexity.
Second, there has been too little accumulation and validation of knowledge from
scientific research owing to the dominance of cross-sectional studies, and the
lack of coordinated research agendas using these approaches in order to confirm
empirical findings. Hence, there is little evidence indicating that public
policies in both the housing and the public health sectors in specific localities
have benefited from the accumulated evidence of empirical research. Third, the
findings from empirical studies have been published in academic journals and
monographs but rarely disseminated to actors and institutions in the public and
private sectors. Hence housing and health research and policy formulation have
not been consolidated during the last three decades. The author of this
communication argues for a radical shift from conventional disciplinary and multi
disciplinary contributions to transdisciplinary research programmes and projects
that formulate and apply innovative approaches founded on conceptual frameworks
that apply systems thinking for the integration of knowledge and know-how of
researchers, policy makers, and professional practitioners in precise localities.
PMID- 28704944
TI - Sphenostylis stenocarpa (ex. A. Rich.) Harms., a Fading Genetic Resource in a
Changing Climate: Prerequisite for Conservation and Sustainability.
AB - The southeastern part of Nigeria is one of the major hotspots of useful plant
genetic resources. These endemic species are associated with a rich indigenous
knowledge and cultural diversity in relation to their use and conservation.
Sphenostylis stenocarpa (ex. A. Rich.) Harms., (African Yam Bean (AYB)), is one
such crop within the family of Fabaceae. Its nutritional and eco-friendly
characteristics have value in ameliorating malnutrition, hidden hunger and
environmental degradation inherent in resource-poor rural and semi-rural
communities throughout Africa. However, lack of information from the custodians
of this crop is limiting its sustainable development. Therefore, ethnobotanical
surveys on the diversity, uses, and constraints limiting the cultivation and use
of the crop in southeastern Nigeria were carried out. Five-hundred respondents
were randomly selected and data collected through oral interviews and focused
group discussion (FGD). Semi-structured questionnaires (SSQ) were also used to
elicit information from a spectrum of AYB users comprising community leaders,
farmers, market women and consumers in five States. Results showed that the
majority of the respondents lacked formal education and were of the age group of
40-50 years, while the female gender dominated with limited access to land and
extension officers. Seed coat colour largely determined utilization. Long cooking
time, requirement for staking materials, aging of farmers and low market demand
were among the major constraints limiting further cultivation and utilization of
AYB. In-situ conservation was by hanging dried fruits by the fireside, beside the
house, storing in earthenware, calabash gourds, cans and bottles. It is concluded
that there is urgent need to scale up conservation through robust linkages
between contemporary scientific domains and indigenous peoples in order to
harness and incorporate the rich indigenous knowledge in local communities for
enhanced scientific knowledge, biodiversity conservation and its sustainable
utilization for food security.
PMID- 28704945
TI - A Study on the Data Compression Technology-Based Intelligent Data Acquisition
(IDAQ) System for Structural Health Monitoring of Civil Structures.
AB - In this paper, a data compression technology-based intelligent data acquisition
(IDAQ) system was developed for structural health monitoring of civil structures,
and its validity was tested using random signals (El-Centro seismic waveform).
The IDAQ system was structured to include a high-performance CPU with large
dynamic memory for multi-input and output in a radio frequency (RF) manner. In
addition, the embedded software technology (EST) has been applied to it to
implement diverse logics needed in the process of acquiring, processing and
transmitting data. In order to utilize IDAQ system for the structural health
monitoring of civil structures, this study developed an artificial filter bank by
which structural dynamic responses (acceleration) were efficiently acquired, and
also optimized it on the random El-Centro seismic waveform. All techniques
developed in this study have been embedded to our system. The data compression
technology-based IDAQ system was proven valid in acquiring valid signals in a
compressed size.
PMID- 28704946
TI - Exploring Autophagy in Drosophila.
AB - Autophagy is a catabolic process in eukaryotic cells promoting bulk or selective
degradation of cellular components within lysosomes. In recent decades, several
model systems were utilized to dissect the molecular machinery of autophagy and
to identify the impact of this cellular "self-eating" process on various
physiological and pathological processes. Here we briefly discuss the advantages
and limitations of using the fruit fly Drosophila melanogaster, a popular model
in cell and developmental biology, to apprehend the main pathway of autophagy in
a complete animal.
PMID- 28704947
TI - Sponge-Inspired Dibromohemibastadin Prevents and Disrupts Bacterial Biofilms
without Toxicity.
AB - Since the banning of several families of compounds in antifouling (AF) coatings,
the search for environmentally friendly AF compounds has intensified. Natural
sources of AF compounds have been identified in marine organisms and can be used
to create analogues in laboratory. In a previous study, we identified that
dibromohemibastadin-1 (DBHB) is a promising AF molecule, leading to the
inhibition of the activity of phenoloxidase, an enzyme involved in the attachment
of mussels to surfaces. This paper describes the activity of the DBHB on biofilm
formation and its detachment and on bacterial adhesion and communication: quorum
sensing. DBHB has an anti-biofilm activity without affecting adhesion of marine
and terrestrial bacteria at a dose of 10 uM. Moreover, DBHB activity on quorum
sensing (QS) is demonstrated at doses of 8 and 16 uM. The activity of DBHB on QS
is compared to kojic acid, a quorum sensing inhibitor already described. This
compound is a promising environmentally friendly molecule potentially useful for
the inhibition of microfouling.
PMID- 28704948
TI - Sea Ice Detection Based on Differential Delay-Doppler Maps from UK TechDemoSat-1.
AB - Global Navigation Satellite System (GNSS) signals can be exploited to remotely
sense atmosphere and land and ocean surface to retrieve a range of geophysical
parameters. This paper proposes two new methods, termed as power-summation of
differential Delay-Doppler Maps (PS-D) and pixel-number of differential Delay
Doppler Maps (PN-D), to distinguish between sea ice and sea water using
differential Delay-Doppler Maps (dDDMs). PS-D and PN-D make use of power
summation and pixel-number of dDDMs, respectively, to measure the degree of
difference between two DDMs so as to determine the transition state (water-water,
water-ice, ice-ice and ice-water) and hence ice and water are detected. Moreover,
an adaptive incoherent averaging of DDMs is employed to improve the computational
efficiency. A large number of DDMs recorded by UK TechDemoSat-1 (TDS-1) over the
Arctic region are used to test the proposed sea ice detection methods. Through
evaluating against ground-truth measurements from the Ocean Sea Ice SAF, the
proposed PS-D and PN-D methods achieve a probability of detection of 99.72% and
99.69% respectively, while the probability of false detection is 0.28% and 0.31%
respectively.
PMID- 28704949
TI - Surrendered and Stray Dogs in Australia-Estimation of Numbers Entering Municipal
Pounds, Shelters and Rescue Groups and Their Outcomes.
AB - There is no national system for monitoring numbers of dogs entering municipal
council pounds and shelters in Australia, or their outcomes. This limits
understanding of the surrendered and stray dog issue, and prevents the evaluation
of management strategies. We aimed to estimate these in 2012-2013. Dog intake and
outcome data were collected for municipal councils and animal welfare
organizations using annual reports, publications, primary peer-reviewed journal
articles, websites and direct correspondence. More comprehensive data were
obtained for New South Wales, Victoria, South Australia and Australian Capital
Territory, whereas it was necessary to impute some or all data for Western
Australia, Northern Territory, Queensland and Tasmania, as data were
incomplete/unavailable. A refined methodology was developed to address the
numerous limitations of the available data. An estimated national total of
211,655 dog admissions (9.3 admissions/1000 residents) occurred in 2012-2013. Of
these admissions, the numbers where the dog was reclaimed, rehomed or euthanized
were estimated as 4.4, 2.9 and 1.9/1000 residents, respectively. Differences in
outcomes were evident between states, and between municipal councils, welfare
organizations and rescue groups. This study emphasizes the need for an ongoing
standardized monitoring system with appropriate data routinely collected from all
municipal councils, animal welfare organizations and rescue groups in Australia.
Such a system would only require data that are easily collected by all relevant
organizations and could be implemented at relatively low cost. This could
facilitate ongoing evaluation of the magnitude of the surrendered and stray dog
problem, and allow assessment of strategies aiming to reduce numbers of
admissions and euthanasia.
PMID- 28704950
TI - Structure-Activity Relationships of Acyclic Selenopurine Nucleosides as Antiviral
Agents.
AB - A series of acyclic selenopurine nucleosides 3a-f and 4a-g were synthesized based
on the bioisosteric rationale between oxygen and selenium, and then evaluated for
antiviral activity. Among the compounds tested, seleno-acyclovir (4a) exhibited
the most potent anti-herpes simplex virus (HSV)-1 (EC50 = 1.47 uM) and HSV-2
(EC50 = 6.34 uM) activities without cytotoxicity up to 100 uM, while 2,6
diaminopurine derivatives 4e-g exhibited significant anti-human cytomegalovirus
(HCMV) activity, which is slightly more potent than the guanine derivative 4d,
indicating that they might act as prodrugs of seleno-ganciclovir (4d).
PMID- 28704951
TI - The Paradox of Ingestion of Dietary Cholesterol in "Vegans".
PMID- 28704952
TI - The Inhibitory Effect of Tartary Buckwheat Extracts on Adipogenesis and
Inflammatory Response.
AB - Tartary buckwheat (Fagopyrum tataricum) has been established globally as a
nutritionally important food item, particularly owing to high levels of bioactive
compounds such as rutin. This study investigated the effect of tartary buckwheat
extracts (TBEs) on adipogenesis and inflammatory response in 3T3-L1 cells. TBEs
inhibited lipid accumulation, triglyceride content, and glycerol-3-phosphate
dehydrogenase (GPDH) activity during adipocyte differentiation of 3T3 L1 cells.
The mRNA levels of genes involved in fatty acid synthesis, such as peroxisome
proliferator-activated receptor-gamma (PPAR-gamma), CCAAT/enhancer binding
protein-alpha (CEBP-alpha), adipocyte protein 2 (aP2), acetyl-CoA carboxylase
(ACC), fatty acid synthase (FAS), and stearoylcoenzyme A desaturase-1 (SCD-1),
were suppressed by TBEs. They also reduced the mRNA levels of inflammatory
mediators such as tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6),
monocyte chemoattractant protein 1 (MCP-1), and inducible nitric oxide synthase
(iNOS). In addition, TBEs were decreased nitric oxide (NO) production. These
results suggest that TBEs may inhibit adipogenesis and inflammatory response;
therefore, they seem to be beneficial as a food ingredient to prevent obesity
associated inflammation.
PMID- 28704953
TI - Sugar Metabolism in Hummingbirds and Nectar Bats.
AB - Hummingbirds and nectar bats coevolved with the plants they visit to feed on
floral nectars rich in sugars. The extremely high metabolic costs imposed by
small size and hovering flight in combination with reliance upon sugars as their
main source of dietary calories resulted in convergent evolution of a suite of
structural and functional traits. These allow high rates of aerobic energy
metabolism in the flight muscles, fueled almost entirely by the oxidation of
dietary sugars, during flight. High intestinal sucrase activities enable high
rates of sucrose hydrolysis. Intestinal absorption of glucose and fructose occurs
mainly through a paracellular pathway. In the fasted state, energy metabolism
during flight relies on the oxidation of fat synthesized from previously-ingested
sugar. During repeated bouts of hover-feeding, the enhanced digestive capacities,
in combination with high capacities for sugar transport and oxidation in the
flight muscles, allow the operation of the "sugar oxidation cascade", the pathway
by which dietary sugars are directly oxidized by flight muscles during exercise.
It is suggested that the potentially harmful effects of nectar diets are
prevented by locomotory exercise, just as in human hunter-gatherers who consume
large quantities of honey.
PMID- 28704954
TI - Docosahexaenoic Acid Inhibits Cerulein-Induced Acute Pancreatitis in Rats.
AB - Oxidative stress is an important regulator in the pathogenesis of acute
pancreatitis (AP). Reactive oxygen species induce activation of inflammatory
cascades, inflammatory cell recruitment, and tissue damage. NF-kappaB regulates
inflammatory cytokine gene expression, which induces an acute, edematous form of
pancreatitis. Protein kinase C delta (PKCdelta) activates NF-kappaB as shown in a
mouse model of cerulein-induced AP. Docosahexaenoic acid (DHA), an omega-3 fatty
acid, exerts anti-inflammatory and antioxidant effects in various cells and
tissues. This study investigated whether DHA inhibits cerulein-induced AP in rats
by assessing pancreatic edema, myeloperoxidase activity, levels of lipid peroxide
and IL-6, activation of NF-kappaB and PKCdelta, and by histologic observation. AP
was induced by intraperitoneal injection (i.p.) of cerulein (50 MUg/kg) every
hour for 7 h. DHA (13 mg/kg) was administered i.p. for three days before AP
induction. Pretreatment with DHA reduced cerulein-induced activation of NF
kappaB, PKCdelta, and IL-6 in pancreatic tissues of rats. DHA suppressed
pancreatic edema and decreased the abundance of lipid peroxide, myeloperoxidase
activity, and inflammatory cell infiltration into the pancreatic tissues of
cerulein-stimulated rats. Therefore, DHA may help prevent the development of
pancreatitis by suppressing the activation of NF-kappaB and PKCdelta, expression
of IL-6, and oxidative damage to the pancreas.
PMID- 28704955
TI - Day-Ahead PM2.5 Concentration Forecasting Using WT-VMD Based Decomposition Method
and Back Propagation Neural Network Improved by Differential Evolution.
AB - Accurate PM2.5 concentration forecasting is crucial for protecting public health
and atmospheric environment. However, the intermittent and unstable nature of
PM2.5 concentration series makes its forecasting become a very difficult task. In
order to improve the forecast accuracy of PM2.5 concentration, this paper
proposes a hybrid model based on wavelet transform (WT), variational mode
decomposition (VMD) and back propagation (BP) neural network optimized by
differential evolution (DE) algorithm. Firstly, WT is employed to disassemble the
PM2.5 concentration series into a number of subsets with different frequencies.
Secondly, VMD is applied to decompose each subset into a set of variational modes
(VMs). Thirdly, DE-BP model is utilized to forecast all the VMs. Fourthly, the
forecast value of each subset is obtained through aggregating the forecast
results of all the VMs obtained from VMD decomposition of this subset. Finally,
the final forecast series of PM2.5 concentration is obtained by adding up the
forecast values of all subsets. Two PM2.5 concentration series collected from
Wuhan and Tianjin, respectively, located in China are used to test the
effectiveness of the proposed model. The results demonstrate that the proposed
model outperforms all the other considered models in this paper.
PMID- 28704956
TI - Rapid and Direct VHH and Target Identification by Staphylococcal Surface Display
Libraries.
AB - Unbiased and simultaneous identification of a specific antibody and its target
antigen has been difficult without prior knowledge of at least one interaction
partner. Immunization with complex mixtures of antigens such as whole organisms
and tissue extracts including tumoral ones evokes a highly diverse immune
response. During such a response, antibodies are generated against a variety of
epitopes in the mixture. Here, we propose a surface display design that is suited
to simultaneously identify camelid single domain antibodies and their targets.
Immune libraries of single-domain antigen recognition fragments from camelid
heavy chain-only antibodies (VHH) were attached to the peptidoglycan of Gram
positive Staphylococcus aureus employing its endogenous housekeeping sortase
enzyme. The sortase transpeptidation reaction covalently attached the VHH to the
bacterial peptidoglycan. The reversible nature of the reaction allowed the
recovery of the VHH from the bacterial surface and the use of the VHH in
downstream applications. These staphylococcal surface display libraries were used
to rapidly identify VHH as well as their targets by immunoprecipitation (IP). Our
novel bacterial surface display platform was stable under harsh screening
conditions, allowed fast target identification, and readily permitted the
recovery of the displayed VHH for downstream analysis.
PMID- 28704957
TI - Chromosomally Integrated Human Herpesvirus 6: Models of Viral Genome Release from
the Telomere and Impacts on Human Health.
AB - Human herpesvirus 6A and 6B, alongside some other herpesviruses, have the
striking capacity to integrate into telomeres, the terminal repeated regions of
chromosomes. The chromosomally integrated forms, ciHHV-6A and ciHHV-6B, are
proposed to be a state of latency and it has been shown that they can both be
inherited if integration occurs in the germ line. The first step in full viral
reactivation must be the release of the integrated viral genome from the telomere
and here we propose various models of this release involving transcription of the
viral genome, replication fork collapse, and t-circle mediated release. In this
review, we also discuss the relationship between ciHHV-6 and the telomere
carrying the insertion, particularly how the presence and subsequent partial or
complete release of the ciHHV-6 genome may affect telomere dynamics and the risk
of disease.
PMID- 28704958
TI - Modeling Nitrogen Dynamics in a Waste Stabilization Pond System Using Flexible
Modeling Environment with MCMC.
AB - This study presents an approach for obtaining realization sets of parameters for
nitrogen removal in a pilot-scale waste stabilization pond (WSP) system. The
proposed approach was designed for optimal parameterization, local sensitivity
analysis, and global uncertainty analysis of a dynamic simulation model for the
WSP by using the R software package Flexible Modeling Environment (R-FME) with
the Markov chain Monte Carlo (MCMC) method. Additionally, generalized likelihood
uncertainty estimation (GLUE) was integrated into the FME to evaluate the major
parameters that affect the simulation outputs in the study WSP. Comprehensive
modeling analysis was used to simulate and assess nine parameters and
concentrations of ON-N, NH3-N and NO3-N. Results indicate that the integrated FME
GLUE-based model, with good Nash-Sutcliffe coefficients (0.53-0.69) and
correlation coefficients (0.76-0.83), successfully simulates the concentrations
of ON-N, NH3-N and NO3-N. Moreover, the Arrhenius constant was the only parameter
sensitive to model performances of ON-N and NH3-N simulations. However,
Nitrosomonas growth rate, the denitrification constant, and the maximum growth
rate at 20 degrees C were sensitive to ON-N and NO3-N simulation, which was
measured using global sensitivity.
PMID- 28704959
TI - Cross Deployment Networking and Systematic Performance Analysis of Underwater
Wireless Sensor Networks.
AB - Underwater wireless sensor networks (UWSNs) have become a new hot research area.
However, due to the work dynamics and harsh ocean environment, how to obtain an
UWSN with the best systematic performance while deploying as few sensor nodes as
possible and setting up self-adaptive networking is an urgent problem that needs
to be solved. Consequently, sensor deployment, networking, and performance
calculation of UWSNs are challenging issues, hence the study in this paper
centers on this topic and three relevant methods and models are put forward.
Firstly, the normal body-centered cubic lattice to cross body-centered cubic
lattice (CBCL) has been improved, and a deployment process and topology
generation method are built. Then most importantly, a cross deployment networking
method (CDNM) for UWSNs suitable for the underwater environment is proposed.
Furthermore, a systematic quar-performance calculation model (SQPCM) is proposed
from an integrated perspective, in which the systematic performance of a UWSN
includes coverage, connectivity, durability and rapid-reactivity. Besides,
measurement models are established based on the relationship between systematic
performance and influencing parameters. Finally, the influencing parameters are
divided into three types, namely, constraint parameters, device performance and
networking parameters. Based on these, a networking parameters adjustment method
(NPAM) for optimized systematic performance of UWSNs has been presented. The
simulation results demonstrate that the approach proposed in this paper is
feasible and efficient in networking and performance calculation of UWSNs.
PMID- 28704960
TI - Fabrication of Flexible Arrayed Lactate Biosensor Based on Immobilizing LDH-NAD+
on NiO Film Modified by GO and MBs.
AB - We proposed the flexible arrayed lactate biosensor based on immobilizing l
lactate dehydrogenase (LDH) and nicotinamide adenine dinucleotide ( NAD + ) on
nickel oxide (NiO) film, and which the average sensitivity could be enhanced by
using graphene oxide (GO) and magnetic beads (MBs). By using GO and MBs, it
exhibits excellent sensitivity (45.397 mV/mM) with a linearity of 0.992 in a
range of 0.2 mM to 3 mM. According to the results of electrochemical impedance
spectroscopy (EIS), the electron transfer resistance of LDH- NAD +
MBs/GPTS/GO/NiO film was smaller than those of LDH-NAD+/GPTS/GO/NiO film and LDH-
NAD + /GPTS/NiO film, and it presented the outstanding electron transfer ability.
After that, the limit of detection, anti-interference effect and bending test
were also investigated.
PMID- 28704961
TI - Extraction of Pathogenesis-Related Proteins and Phenolics in Sauvignon Blanc as
Affected by Grape Harvesting and Processing Conditions.
AB - Thaumatin-like proteins (TLPs) and chitinases are the two main groups of
pathogenesis-related (PR) proteins found in wine that cause protein haze
formation. Previous studies have found that phenolics are also involved in
protein haze formation. In this study, Sauvignon Blanc grapes were harvested and
processed in two vintages (2011 and 2012) by three different treatments: (1) hand
harvesting with whole bunch press (H-WB); (2) hand harvesting with destem/crush
and 3 h skin contact (H-DC-3); and (3) machine harvesting with destem/crush and 3
h skin contact (M-DC-3). The juices were collected at three pressure levels (0.4
MPa, 0.8 MPa and 1.6 MPa), some juices were fermented in 750 mL of wine bottles
to determine the bentonite requirement for the resulting wines. Results showed
juices of M-DC-3 had significantly lower concentration of proteins, including PR
proteins, compared to those of H-DC-3, likely due to the greater juice yield of M
DC-3 and interactions between proteins and phenolics. Juices from the 0.8-1.6 MPa
pressure and resultant wines had the highest concentration of phenolics but the
lowest concentration of TLPs. This supported the view that TLPs are released at
low pressure as they are mainly present in grape pulp but additional extraction
of phenolics largely present in skin occurs at higher pressing pressure. Wine
protein stability tests showed a positive linear correlation between bentonite
requirement and the concentration of chitinases, indicating the possibility of
predicting bentonite requirement by quantification of chitinases. This study
contributes to an improved understanding of extraction of haze-forming PR
proteins and phenolics that can influence bentonite requirement for protein
stabilization.
PMID- 28704962
TI - SIRT3: Oncogene and Tumor Suppressor in Cancer.
AB - Sirtuin 3 (SIRT3), the major deacetylase in mitochondria, plays a crucial role in
modulating oxygen reactive species (ROS) and limiting the oxidative damage in
cellular components. SIRT3 targets different enzymes which regulate mitochondrial
metabolism and participate in ROS detoxification, such as the complexes of the
respiratory chain, the isocitrate dehydrogenase, or the manganese superoxide
dismutase. Thus, SIRT3 activity is essential in maintaining mitochondria
homeostasis and has recently received great attention, as it is considered a
fidelity protein for mitochondrial function. In some types of cancer, SIRT3
functions as a tumoral promoter, since it keeps ROS levels under a certain
threshold compatible with cell viability and proliferation. On the contrary,
other studies describe SIRT3 as a tumoral suppressor, as SIRT3 could trigger cell
death under stress conditions. Thus, SIRT3 could have a dual role in cancer. In
this regard, modulation of SIRT3 activity could be a new target to develop more
personalized therapies against cancer.
PMID- 28704963
TI - Challenges in Wireless System Integration as Enablers for Indoor Context Aware
Environments.
AB - The advent of fully interactive environments within Smart Cities and Smart
Regions requires the use of multiple wireless systems. In the case of user-device
interaction, which finds multiple applications such as Ambient Assisted Living,
Intelligent Transportation Systems or Smart Grids, among others, large amount of
transceivers are employed in order to achieve anytime, anyplace and any device
connectivity. The resulting combination of heterogeneous wireless network
exhibits fundamental limitations derived from Coverage/Capacity relations, as a
function of required Quality of Service parameters, required bit rate, energy
restrictions and adaptive modulation and coding schemes. In this context,
inherent transceiver density poses challenges in overall system operation, given
by multiple node operation which increases overall interference levels. In this
work, a deterministic based analysis applied to variable density wireless sensor
network operation within complex indoor scenarios is presented, as a function of
topological node distribution. The extensive analysis derives interference
characterizations, both for conventional transceivers as well as wearables, which
provide relevant information in terms of individual node configuration as well as
complete network layout.
PMID- 28704964
TI - Myrcia splendens (Sw.) DC. (syn. M. fallax (Rich.) DC.) (Myrtaceae) Essential Oil
from Amazonian Ecuador: A Chemical Characterization and Bioactivity Profile.
AB - In this study, we performed the chemical characterization of Myrcia splendens
(Sw.) DC. (Myrtaceae) essential oil from Amazonian Ecuador and the assessment of
its bioactivity in terms of cytotoxic, antibacterial, and antioxidant activity as
starting point for possible applicative uses. M. splendens essential oil,
obtained by hydro-distillation, was analyzed by Gas Chromatography-Mass
Spectrometry (GC-MS) and Gas Chromatography-Flame Ionization Detector (GC-FID):
the major components were found to be trans-nerolidol (67.81%) and alpha
bisabolol (17.51%). Furthermore, we assessed the cytotoxic activity against MCF-7
(breast), A549 (lung) human tumor cell lines, and HaCaT (human keratinocytes) non
tumor cell line through 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium
bromide (MTT) test: promising results in terms of selectivity and efficacy
against the MCF-7 cell line (IC50 of 5.59 +/- 0.13 MUg/mL at 48 h) were obtained,
mainly due to alpha-bisabolol. Furthermore, antibacterial activity against Gram
positive and negative bacteria were performed through High Performance Thin Layer
Chromatography (HPTLC) bioautographic assay and microdilution method: trans
nerolidol and beta-cedren-9-one were the main molecules responsible for the low
antibacterial effects against human pathogens. Nevertheless, interesting values
of Minimum Inhibitory Concentration (MIC) were noticeable against phytopathogen
strains. Radical scavenging activity performed by HPTLC bioautographic and
spectrophotometric 1,1-diphenyl-2-picrylhydrazyl (DPPH) approaches were
negligible. In conclusion, the essential oil revealed a good potential for plant
defense and anti-cancer applications.
PMID- 28704965
TI - Progress Evaluation for the Restaurant Industry Assessed by a Voluntary Marketing
Mix and Choice-Architecture Framework That Offers Strategies to Nudge American
Customers toward Healthy Food Environments, 2006-2017.
AB - Consumption of restaurant food and beverage products high in fat, sugar and
sodium contribute to obesity and non-communicable diseases. We evaluated
restaurant-sector progress to promote healthy food environments for Americans. We
conducted a desk review of seven electronic databases (January 2006-January 2017)
to examine restaurant strategies used to promote healthful options in the United
States (U.S.). Evidence selection (n = 84) was guided by the LEAD principles
(i.e., locate, evaluate, and assemble evidence to inform decisions) and verified
by data and investigator triangulation. A marketing-mix and choice-architecture
framework was used to examine eight voluntary strategies (i.e., place, profile,
portion, pricing, promotion, healthy default picks, priming or prompting and
proximity) to evaluate progress (i.e., no, limited, some or extensive) toward 12
performance metrics based on available published evidence. The U.S. restaurant
sector has made limited progress to use pricing, profile (reformulation), healthy
default picks (choices), promotion (responsible marketing) and priming and
prompting (information and labeling); and some progress to reduce portions. No
evidence was available to assess progress for place (ambience) and proximity
(positioning) to promote healthy choices during the 10-year review period. Chain
and non-chain restaurants can apply comprehensive marketing-mix and nudge
strategies to promote healthy food environments for customers.
PMID- 28704967
TI - Variability in DNA Repair Capacity Levels among Molecular Breast Cancer Subtypes:
Triple Negative Breast Cancer Shows Lowest Repair.
AB - Breast cancer (BC) is a heterogeneous disease which many studies have classified
in at least four molecular subtypes: Luminal A, Luminal B, HER2-Enriched, and
Basal-like (including triple-negative breast cancer, TNBC). These subtypes
provide information to stratify patients for better prognostic predictions and
treatment selection. Individuals vary in their sensitivities to carcinogens due
to differences in their DNA repair capacity (DRC) levels. Although our previous
case-control study established low DRC (in terms of NER pathway) as a BC risk
factor, we aim to study this effect among the molecular subtypes. Therefore, the
objectives of this study include investigating whether DRC varies among molecular
subtypes and testing any association regarding DRC. This study comprised 267
recently diagnosed women with BC (cases) and 682 without BC (controls). Our
results show a substantial variability in DRC among the molecular subtypes, with
TNBC cases (n = 47) having the lowest DRC (p-value < 0.05). Almost 80 percent of
BC cases had a DRC below the median (4.3%). Low DRC was strongly associated with
the TNBC subtype (OR 7.2; 95% CI 3.3, 15.7). In conclusion, our study provides
the first report on the variability among the molecular subtypes and provides a
hypothesis based on DRC levels for the poor prognosis of TNBC.
PMID- 28704966
TI - The Role of Ghrelin and Ghrelin Signaling in Aging.
AB - With our aging society, more people hope for a long and healthy life. In recent
years, researchers have focused on healthy longevity factors. In particular,
calorie restriction delays aging, reduces mortality, and extends life. Ghrelin,
which is secreted during fasting, is well known as an orexigenic peptide. Because
ghrelin is increased by caloric restriction, ghrelin may play an important role
in the mechanism of longevity mediated by calorie restriction. In this review, we
will discuss the role of orexigenic peptides with a particular focus on ghrelin.
We conclude that the ghrelin-growth hormone secretagogue-R signaling pathway may
play an important role in the anti-aging mechanism.
PMID- 28704969
TI - Urban Green Space Perception and Its Contribution to Well-Being.
AB - Individual perceptions are essential when evaluating the well-being benefits from
urban green spaces. This study predicted the influence of perceived green space
characteristics in the city of Szeged, Hungary, on two well-being variables: the
green space visitors' level of satisfaction and the self-reported quality of
life. The applied logistic regression analysis used nine predictors: seven
perceived green space characteristics from a questionnaire survey among visitors
of five urban green spaces of Szeged; and the frequency of green space visitors'
crowd-sourced recreational running paths and photographs picturing green space
aesthetics. Results revealed that perceived green space characteristics with
direct well-being benefits were strong predictors of both dependent variables.
Perceived green space characteristics with indirect, yet fundamental, well-being
benefits, namely, regulating ecosystem services had minor influence on the
dependent variables. The crowd-sourced geo-tagged data predicted only the
perceived quality of life contributions; but revealed spatial patterns of
recreational green space use and aesthetics. This study recommends that
regulating ecosystem services should be planned with a focus on residents'
aesthetic and recreational needs. Further research on the combination of green
space visitors' perceptions and crowd-sourced geo-tagged data is suggested to
promote planning for well-being and health benefits of urban green spaces.
PMID- 28704970
TI - Integrating Mental and Physical Health Care for Low-Income Americans: Assessing a
Federal Program's Initial Impact on Access and Cost.
AB - Individuals with mental health disorders often die decades earlier than the
average person, and low-income individuals disproportionately experience limited
access to necessary services. In 2014, the U.S. Health Resources & Services
Administration (HRSA) leveraged Affordable Care Act funds to address these
challenges through behavioral health integration. The objective of this study is
to assess the US$55 million program's first-year impact on access and cost. This
analysis uses multivariable difference-in-difference regression models to
estimate changes in outcomes between the original 219 Federally Qualified Health
Center (FQHC) Behavioral Health Integration grantees and two comparison groups.
The primary outcome variables are annual depression screening rate, percentage of
mental health and substance use patients served, and per capita cost. The results
change when comparing the Behavioral Health Integration (BHI) grantees to a
propensity score-matched comparison group versus comparing the grantees to the
full population of health centers. After one year of implementation, the grant
program appeared ineffective as measured by this study's outcomes, though costs
did not significantly rise because of the program. This study has limitations
that must be discussed, including non-randomized study design, FQHC data
measurement, and BHI program design consequences. Time will tell if FQHC-based
behavioral-physical health care integration will improve access among low-income,
medically-underserved populations.
PMID- 28704968
TI - Epigenetic Modifications and Head and Neck Cancer: Implications for Tumor
Progression and Resistance to Therapy.
AB - Head and neck squamous carcinoma (HNSCC) is the sixth most prevalent cancer and
one of the most aggressive malignancies worldwide. Despite continuous efforts to
identify molecular markers for early detection, and to develop efficient
treatments, the overall survival and prognosis of HNSCC patients remain poor.
Accumulated scientific evidences suggest that epigenetic alterations, including
DNA methylation, histone covalent modifications, chromatin remodeling and non
coding RNAs, are frequently involved in oral carcinogenesis, tumor progression,
and resistance to therapy. Epigenetic alterations occur in an unsystematic manner
or as part of the aberrant transcriptional machinery, which promotes selective
advantage to the tumor cells. Epigenetic modifications also contribute to
cellular plasticity during tumor progression and to the formation of cancer stem
cells (CSCs), a small subset of tumor cells with self-renewal ability. CSCs are
involved in the development of intrinsic or acquired therapy resistance, and
tumor recurrences or relapse. Therefore, the understanding and characterization
of epigenetic modifications associated with head and neck carcinogenesis, and the
prospective identification of epigenetic markers associated with CSCs, hold the
promise for novel therapeutic strategies to fight tumors. In this review, we
focus on the current knowledge on epigenetic modifications observed in HNSCC and
emerging Epi-drugs capable of sensitizing HNSCC to therapy.
PMID- 28704971
TI - Isolation and Characterization of Aphidicolin Derivatives from Tolypocladium
inflatum.
AB - Inflatin G (1), a new aphidicolin analogue, together with seven known compounds
inflatin A (2), inflatin B (3), aphidicolin (4), aphidicolin-17-monoacetate (5),
gulypyrone A (6), pyridoxatin rotamers A (7) and B (8), were isolated from the
ascomycete fungus Tolypocladium inflatum. Their structures were determined
through NMR analyses and the circular dichroism data of the in situ formed
[Rh2(OCOCF3)4] complexes. Compounds 1, 4, 5, 7, and 8 showed modest cytotoxicity
against four human cancer cell lines A549, CNE1-MP1, A375, and MCF-7.
PMID- 28704972
TI - Impact of First Aid on Treatment Outcomes for Non-Fatal Injuries in Rural
Bangladesh: Findings from an Injury and Demographic Census.
AB - Non-fatal injuries have a significant impact on disability, productivity, and
economic cost, and first-aid can play an important role in improving non-fatal
injury outcomes. Data collected from a census conducted as part of a drowning
prevention project in Bangladesh was used to quantify the impact of first-aid
provided by trained and untrained providers on non-fatal injuries. The census
covered approximately 1.2 million people from 7 sub-districts of Bangladesh.
Around 10% individuals reported an injury event in the six-month recall period.
The most common injuries were falls (39%) and cuts injuries (23.4%). Overall,
81.7% of those with non-fatal injuries received first aid from a provider of whom
79.9% were non-medically trained. Individuals who received first-aid from a
medically trained provider had more severe injuries and were 1.28 times more
likely to show improvement or recover compared to those who received first-aid
from an untrained provider. In Bangladesh, first-aid for non-fatal injuries are
primarily provided by untrained providers. Given the large number of untrained
providers and the known benefits of first aid to overcome morbidities associated
with non-fatal injuries, public health interventions should be designed and
implemented to train and improve skills of untrained providers.
PMID- 28704973
TI - The Mode of Action of Cyclo(l-Ala-l-Pro) in Inhibiting Aflatoxin Production of
Aspergillus flavus.
AB - Cyclo(l-Ala-l-Pro) inhibits aflatoxin production in aflatoxigenic fungi without
affecting fungal growth. The mode of action of cyclo(l-Ala-l-Pro) in inhibiting
aflatoxin production of Aspergillus flavus was investigated. A glutathione S
transferase (GST) of the fungus, designated AfGST, was identified as a binding
protein of cyclo(l-Ala-l-Pro) in an experiment performed using cyclo(l-Ala-l-Pro)
immobilized Sepharose beads. Cyclo(l-Ala-l-Pro) specifically bound to recombinant
AfGST and inhibited its GST activity. Ethacrynic acid, a known GST inhibitor,
inhibited the GST activity of recombinant AfGST and aflatoxin production of the
fungus. Ethacrynic acid reduced the expression level of AflR, a key regulatory
protein for aflatoxin production, similar to cyclo(l-Ala-l-Pro). These results
suggest that cyclo(l-Ala-l-Pro) inhibits aflatoxin production by affecting GST
function in A. flavus, and that AfGST inhibitors are possible candidates as
selective aflatoxin production inhibitors.
PMID- 28704974
TI - Genotypic Regulation of Aflatoxin Accumulation but Not Aspergillus Fungal Growth
upon Post-Harvest Infection of Peanut (Arachis hypogaea L.) Seeds.
AB - Aflatoxin contamination is a major economic and food safety concern for the
peanut industry that largely could be mitigated by genetic resistance. To screen
peanut for aflatoxin resistance, ten genotypes were infected with a green
fluorescent protein (GFP)-expressing Aspergillus flavus strain. Percentages of
fungal infected area and fungal GFP signal intensity were documented by visual
ratings every 8 h for 72 h after inoculation. Significant genotypic differences
in fungal growth rates were documented by repeated measures and area under the
disease progress curve (AUDPC) analyses. SICIA (Seed Infection Coverage and
Intensity Analyzer), an image processing software, was developed to digitize
fungal GFP signals. Data from SICIA image analysis confirmed visual rating
results validating its utility for quantifying fungal growth. Among the tested
peanut genotypes, NC 3033 and GT-C20 supported the lowest and highest fungal
growth on the surface of peanut seeds, respectively. Although differential fungal
growth was observed on the surface of peanut seeds, total fungal growth in the
seeds was not significantly different across genotypes based on a fluorometric
GFP assay. Significant differences in aflatoxin B levels were detected across
peanut genotypes. ICG 1471 had the lowest aflatoxin level whereas Florida-07 had
the highest. Two-year aflatoxin tests under simulated late-season drought also
showed that ICG 1471 had reduced aflatoxin production under pre-harvest field
conditions. These results suggest that all peanut genotypes support A. flavus
fungal growth yet differentially influence aflatoxin production.
PMID- 28704975
TI - Current Knowledge on the Use of Computational Toxicology in Hazard Assessment of
Metallic Engineered Nanomaterials.
AB - As listed by the European Chemicals Agency, the three elements in evaluating the
hazards of engineered nanomaterials (ENMs) include the integration and evaluation
of toxicity data, categorization and labeling of ENMs, and derivation of hazard
threshold levels for human health and the environment. Assessing the hazards of
ENMs solely based on laboratory tests is time-consuming, resource intensive, and
constrained by ethical considerations. The adoption of computational toxicology
into this task has recently become a priority. Alternative approaches such as
(quantitative) structure-activity relationships ((Q)SAR) and read-across are of
significant help in predicting nanotoxicity and filling data gaps, and in
classifying the hazards of ENMs to individual species. Thereupon, the species
sensitivity distribution (SSD) approach is able to serve the establishment of ENM
hazard thresholds sufficiently protecting the ecosystem. This article critically
reviews the current knowledge on the development of in silico models in
predicting and classifying the hazard of metallic ENMs, and the development of
SSDs for metallic ENMs. Further discussion includes the significance of well
curated experimental datasets and the interpretation of toxicity mechanisms of
metallic ENMs based on reported models. An outlook is also given on future
directions of research in this frontier.
PMID- 28704976
TI - Role of the p-Coumaroyl Moiety in the Antioxidant and Cytoprotective Effects of
Flavonoid Glycosides: Comparison of Astragalin and Tiliroside.
AB - The aim of this study was to explore the role of p-coumaroyl in the antioxidant
and cytoprotective effects of flavonoid glycosides. The antioxidant effects of
astragalin and tiliroside were compared using ferric ion reducing antioxidant
power, DPPH* scavenging, ABTS*+ scavenging, *O2- scavenging, and Fe2+-chelating
assays. The results of these assays revealed that astragalin and tiliroside both
exhibited dose-dependent activities; however, tiliroside exhibited lower IC50
values than astragalin. In the Fe2+-chelating assay, tiliroside gave a larger
shoulder-peak at 510 nm than astragalin, and was also found to be darker in
color. Both of these compounds were subsequently evaluated in a Fenton-induced
mesenchymal stem cell (MSC) damaged assay, where tiliroside performed more
effectively as a cytoprotective agent than astragalin. Tiliroside bearing a 6''-O
p-coumaroyl moiety exhibits higher antioxidant and cytoprotective effects than
astragalin. The 6''-O-p-coumaroyl moiety of tiliroside not only enhances the
possibility of electron-transfer and hydrogen-atom-transfer-based multi-pathways,
but also enhances the likelihood of Fe-chelating. The p-coumaroylation of the 6"
OH position could therefore be regarded as a potential approach for improving the
antioxidant and cytoprotective effects of flavonoid glycosides in MSC
implantation therapy.
PMID- 28704977
TI - A New N-methoxypyridone from the Co-Cultivation of Hawaiian Endophytic Fungi
Camporesia sambuci FT1061 and Epicoccum sorghinum FT1062.
AB - A new N-methoxypyridone analog (1), together with four known compounds, was
isolated from the co-culture of Hawaiian endophytic fungi Camporesia sambuci
FT1061 and Epicoccum sorghinum FT1062. The structure of the new compound was
elucidated as 11S-hydroxy-1-methoxyfusaricide (1) by extensive spectroscopic
analysis and comparison with the literature. The absolute configuration of 1 was
determined by comparison with the experimental and calculated ECD spectra. The
absolute configuration of compound 3 was investigated and renamed as (+)
epipyridone by comparison of the optical rotation and CD spectrum with those of
1. The other known compounds were identified as epicoccarine B (2), D8646-2-6
(4), and iso-D8646-2-6 (5). Compounds 4 and 5 showed modest inhibitory activity
towards pathogenic fungi. Epicoccarine B (2) inhibited A2780 and TK-10 with an
IC50 value of 22 MUM.
PMID- 28704978
TI - Evidences from Rewarding System, FRN and P300 Effect in Internet-Addiction in
Young People SHORT TITLE: Rewarding System and EEG in Internet-Addiction.
AB - The present research explored rewarding bias and attentional deficits in Internet
addiction (IA) based on the IAT (Internet Addiction Test) construct, during an
attentional inhibitory task (Go/NoGo task). Event-related Potentials (ERPs)
effects (Feedback Related Negativity (FRN) and P300) were monitored in
concomitance with Behavioral Activation System (BAS) modulation. High-IAT young
participants showed specific responses to IA-related cues (videos representing
online gambling and videogames) in terms of cognitive performance (decreased
Response Times, RTs; and Error Rates, ERs) and ERPs modulation (decreased FRN and
increased P300). Consistent reward and attentional biases was adduced to explain
the cognitive "gain" effect and the anomalous response in terms of both feedback
behavior (FRN) and attentional (P300) mechanisms in high-IAT. In addition, BAS
and BAS-Reward subscales measures were correlated with both IAT and ERPs
variations. Therefore, high sensitivity to IAT may be considered as a marker of
dysfunctional reward processing (reduction of monitoring) and cognitive control
(higher attentional values) for specific IA-related cues. More generally, a
direct relationship among reward-related behavior, Internet addiction and BAS
attitude was suggested.
PMID- 28704980
TI - Electronic States of Nanocrystal Doped with Oxygen and Visible Emission on Black
Silicon Prepared by ns-Laser.
AB - We fabricated the black silicon (BS) structures by using nanosecond pulsed laser
(ns-laser) in vacuum or in oxygen environment. It is interesting that the
enhanced visible emission occurs in the photoluminescence (PL) spectra measured
at room temperature and at lower temperature on the BS surface after annealing,
in which lasing near 600 nm is observed on the BS surface with Purcell cavity
structure. It is demonstrated in the PL spectra analysis that the electronic
states in the nanocrystal doped with oxygen play a main role in the visible
emission on the BS surface. The origin of the visible emission near 400, 560, or
700 nm is univocally revealed in the PL spectra analysis. A visible emission is
promising for the development of the white light device on the BS.
PMID- 28704981
TI - Corrosion Resistance of Nanopowders of Borides and Carbides of IV-VIB Group
Metals in the Nickeling Electrolytes.
AB - The corrosion resistance of nanopowders of borides and carbides of metals of IV
VIB groups, as well as of silicon carbide, was studied in the standard nickeling
electrolytes. As objects of study, nanopowders with the content of the main phase
91.8-97.6% and with the average particle size 32-78 nm were used. Their corrosion
resistance was evaluated depending on the acidity of the electrolyte,
temperature, and duration of the interaction. It was found that, by the corrosion
resistance in the electrolytes solutions, nanopowders of borides and carbides
within each group of compounds are similar and characterized by unlimited period
of induction in alkaline media. An exception is the nanopowder of silicon carbide
which is resistant to the solution of any acidity.
PMID- 28704979
TI - Electrospun Polymer Nanofibers Decorated with Noble Metal Nanoparticles for
Chemical Sensing.
AB - The integration of different noble metal nanostructures, which exhibit desirable
plasmonic and/or electrocatalytic properties, with electrospun polymer
nanofibers, which display unique mechanical and thermodynamic properties, yields
novel hybrid nanoscale systems of synergistic properties and functions. This
review summarizes recent advances on how to incorporate noble metal nanoparticles
into electrospun polymer nanofibers and illustrates how such integration paves
the way towards chemical sensing applications with improved sensitivity,
stability, flexibility, compatibility, and selectivity. It is expected that
further development of this field will eventually make a wide impact on many
areas of research.
PMID- 28704982
TI - Liquid Levodopa/Carbidopa: Old Solution, Forgotten Complication.
PMID- 28704983
TI - A Patient with Recurrent Dyskinesia and Hyperpyrexia Syndrome.
AB - Dyskinesia hyperpyrexia syndrome is a rare medical emergency in Parkinson's
disease. It is characterized by continuous dyskinesia associated with
hyperthermia, rhabdomyolysis, and alteration of the mental state. We present the
case of a 74-year-old woman who presented with recurrent dyskinesia hyperpyrexia
syndrome. Although some provocation factors and clinical manifestations seem to
be shared with parkinsonism hyperpyrexia syndrome, a clear distinction in
management should be considered.
PMID- 28704984
TI - The effect of personal, familial, and environmental characteristics on acne
vulgaris: a prospective, multicenter, case controlled study from Turkey.
AB - BACKGROUND: There are only a few studies about epidemiological features of acne
vulgaris in the literature. The aim of this study was to analyze demographic,
clinical, familial and environmental characteristics of acne, the role of diet
and aggravating factors and association of these factors with acne severity.
METHODS: Patients with a diagnosis of mild-moderate to severe acne were
consecutively interviewed at the participating centers during the study period.
RESULTS: A total of 3826 patients and 759 control patients were involved in this
study. Mild acne was the most common type of acne, and most of the lesions were
localized on face followed by the trunk. The severity of acne was worse in
patients who had a positive family history of acne. The most common triggering
factor was psychological stress. We found a positive correlation with chocolate,
bread, green tea, milk, white sugar, ripe banana, ice cream, apple, orange, and
red meat consumption. As we compare the acne severity according to geographical
features we detected mildmoderate acne was more common in Mediterrenean region
and severe acne was more common in East Anatolian region. Family history
positivity was more common in Aegean region and least common in Middle Anatolian
region. There was statistically significant relationship as we compare acne
severity and dietary factors such as chocolate, dairy products such as milk,
sunflower seed consumption within the geographical regions. CONCLUSIONS: This
study presents the demographic and clinical characteristics of acne patients in
Asian and the European parts of Turkey. We believe that this study will provide a
useful overview of acne in Turkey.
PMID- 28704985
TI - The large spectrum of spitzoid tumours: a retrospective survival study.
AB - BACKGROUND: There is no universally-accepted classification of spitzoid tumours.
This makes difficult to assign a correct diagnosis and select a treatment that
minimises the risk of overestimating, or worse, underestimating, the malignant
potential of these tumours. To describe the clinical-pathological and
epidemiological features of spitzoid tumours, as well as to assess mortality in
these patients. METHODS: This retrospective cohort study looked at data on
spitzoid tumours excised in 1999-2012 at the Dermatologic Clinic of the Turin
University Hospital. Spitzoid melanoma specific survival curves were generated
with the Kaplan-Meier method and compared using the log-rank test. RESULTS: in
this time period, 1663 lesion were described at the pathologic report as
spitzoid. 262 were (15.75%) Spitz naevi, 307 (18.46%) Reed naevi, 827 (49.73%),
810 (48.71%) spitzoid dysplastic naevi, 17(1.02%) atypical spitzoid tumours, and
267 (16.06%) spitzoid melanomas. Median follow up time was 9 years. Out of the
entire cohort only 24 patients died from melanoma. All of them received a
diagnosis of spitzoid melanoma. None of the patients with a diagnosis of not
melanoma spitz tumour died for melanoma during the follow up. CONCLUSION: In the
large mayority of the cases, spitz tumour should be considered as benign lesion
and excised only if melanoma features are seen. The used clinical pathological
classification avoid misdiagnoses, inappropriate treatment and the risk of death
for melanoma.
PMID- 28704986
TI - Desmoplastic melanoma: a diagnostic challenge.
PMID- 28704987
TI - Exacerbated pemphigus vulgaris superinfected with herpes virus II,
chemoattracting a florid inflammatory response.
PMID- 28704988
TI - Acute Generalized Exanthematous Pustulosis (AGEP) associated to Epstein-Barr
Virus (EBV) infection reactivation.
PMID- 28704989
TI - In vitro study of the influence of octocrylene on a selected metastatic melanoma
cell line.
AB - BACKGROUND: Octocrylene (OCT) is one of the most widespread chemical UV filters
used in sunscreens and cosmetic products. Despite the use of sunscreens and
personal care products over decades, melanoma as the most serious and aggressive
form of skin cancer is still a cause of concern. Hence the aim of this study was
to investigate any potential influence of OCT on metabolic activity, cytotoxicity
and ABCB5 mRNA expression in melanoma cells. The ABCB5 transmembrane protein was
tested due to its well-known role in the initiation, invasion and metastatic
spread of various cancers, including melanoma. METHODS: Metastatic melanoma cell
line WM-266-4 (ATCC) was incubated with selected concentrations of OCT and for
different time intervals. The MTT and LDH assays to measure the cells' metabolic
activity and cytotoxicity were used respectively. Target gene (ABCB5) expression
was detected by quantitative real-time PCR (qRT-PCR), using TaqMan(r) chemistry.
RESULTS: Our results suggest decreased metastatic melanoma cells' metabolic
activity, increased cytotoxicity and increased ABCB5 mRNA expression (p<0.05)
with longer time of exposure to OCT as compared to control cells. Accordingly, we
suspect that the surviving cells are more invasive and aggressive, which might
explain their microscopically observed cannibalistic activity. CONCLUSIONS: With
this study, we elucidate a new promising field for further research to contribute
to etiology and prevention of melanoma.
PMID- 28704990
TI - Postfebrile telogen effluvium.
PMID- 28704991
TI - A strange perianal ulcer.
PMID- 28704992
TI - Serum levels of tumor necrosis factor-alpha in patients with psoriasis before,
during and after narrow-band UVB phototherapy.
AB - BACKGROUND: Narrow-band UVB (NB-UVB) phototherapy is widely used worldwide for
moderate and severe psoriasis, which is a chronic autoimmune inflammatory disease
characterized by skin infiltrates of Th1-, Th17- and Th22-cells releasing locally
pro-inflammatory cytokines. We investigate serum levels of tumor necrosis factor
alpha (TNF-alpha) in psoriatic patients before and after NB-UVB phototherapy.
METHODS: Twenty-eight subjects with moderate/severe plaque type psoriasis were
enrolled. The severity of skin involvement was rated according to the Psoriasis
Area and Severity Index (PASI) score at baseline (T0) and after 4 (T1) and 12
(T2) weeks of NB-UVB treatment. At the same time points, blood samples were taken
for evaluation of TNF-alpha levels. NB-UVB phototherapy was administered twice
weekly on non-consecutive days until 12 weeks. RESULTS: The median PASI score
significantly decreased from 12.0 at baseline (T0), to 6.9 after 4 weeks (T1,
P<0.001) and to 0 after 12 weeks (T2, P<0.001). TNF-a serum levels significantly
increased in respect to the baseline after 12 weeks of therapy. CONCLUSIONS: NB
UVB phototherapy is highly effective against psoriasis but, as it increases the
TNF-alpha serum level, it seems unlikely that it can decrease the chronic
inflammatory state that is thought to be responsible of the systemic co
morbidities of psoriasis.
PMID- 28704993
TI - A case of juvenile amyopathic dermatomyositis.
PMID- 28704994
TI - How to improve adherence to treatment in patients with mild-to-moderate
psoriasis.
AB - Topical treatments are frequently used for the therapy of psoriasis. However,
they may be associated with poor adherence in clinical practice. Therapeutic
adherence is affected by patient's characteristics, as well as disease- and
treatment-related factors; moreover, satisfaction with therapy, cosmetic
acceptability, and complexity of the treatment regimen do also play a role. Since
low adherence could lead to treatment failure, it is crucial to elaborate
effective strategies aimed at improving patient adherence and thus clinical
outcomes in psoriasis. To this purpose, here we have addressed several aspects of
dermatological treatment that impact on adherence such as selection of therapy,
selection of vehicle, and physician-patient communication. In addition, possible
practical measures to improve adherence have also been discussed. In this light,
we report that the use of calcipotriol and betamethasone dipropionate (Cal/BD)
fixed-combination gel may be associated with improved patients' preference and
better outcomes compared to similar formulations.
PMID- 28704995
TI - Molecular Dynamics Simulations of Amide Functionalized Imidazolium
Bis(trifluoromethanesulfonyl)imide Dicationic Ionic Liquids.
AB - In the present study, the structure and dynamics of three dicationic ionic
liquids (DILs) with a functional amide group in the imidazolium ring with
bis(trifluoromethanesulfonyl)imide, [TFSI]- anion has been studied by molecular
dynamics (MD) simulations. Densities, radial distribution functions (RDFs),
combined distribution functions (CDFs), spatial distribution functions, mean
square displacements (MSD), and self-diffusivities for the ions have been
calculated from the MD simulations. The calculated densities for
[C4(amim)2][TFSI]2 at different temperatures agreed well with the experimental
values. The calculated RDFs and CDFs show that the anions are well organized
around the amide group and imidazolium rings and the favorite sites of
interaction of the [TFSI]- ion are the hydrogen atoms of the amide group and
hydrogen atoms of the imidazolium ring of the cation. The calculated MSDs
indicated that the diffusion coefficients of the studied DILs are 1 order of
magnitude smaller than those of DILs with a comparable molar mass.
PMID- 28704996
TI - Imidacloprid Promotes High Fat Diet-Induced Adiposity in Female C57BL/6J Mice and
Enhances Adipogenesis in 3T3-L1 Adipocytes via the AMPKalpha-Mediated Pathway.
AB - Imidacloprid, a neonicotinoid insecticide, was previously reported to enhance
adipogenesis and resulted in insulin resistance in cell culture models. It was
also reported to promote high fat diet-induced obesity and insulin resistance in
male C57BL/6J mice. Thus, the goal of the present study was to determine the
effects of imidacloprid and dietary fat interaction on the development of
adiposity and insulin resistance in female C57BL/6J mice. Mice were fed with a
low (4% w/w) or high fat (20% w/w) diet containing imidacloprid (0.06, 0.6, or 6
mg/kg bw/day) for 12 weeks. Mice fed with imidacloprid (0.6 mg/kg bw/day)
significantly enhanced high fat diet-induced weight gain and adiposity. Treatment
with imidacloprid significantly increased serum insulin levels with high fat diet
without effects on other markers of glucose homeostasis. AMPKalpha activation was
significantly inhibited by 0.6 and 6 mg imidacloprid/kg bw/day in white adipose
tissue. Moreover, AMPKalpha activation with 5-aminoimidazole-4-carboxamide
ribonucleotide abolished the effects of imidacloprid (10 MUM) on enhanced
adipogenesis in 3T3-L1 adipocytes. N-Acetyl cysteine also partially reversed the
effects of imidacloprid on reduced phosphorylation of protein kinase B (AKT) in
C2C12 myotubes. These results indicate that imidacloprid may potentiate high fat
diet-induced adiposity in female C57BL/6J mice and enhance adipogenesis in 3T3-L1
adipocytes via the AMPKalpha-mediated pathway. Imidacloprid might also influence
glucose homeostasis partially by inducing cellular oxidative stress in C2C12
myotubes.
PMID- 28704997
TI - Zn/MnO2 Battery Chemistry With H+ and Zn2+ Coinsertion.
AB - Rechargeable aqueous Zn/MnO2 battery chemistry in a neutral or mildly acidic
electrolyte has attracted extensive attention recently because all the components
(anode, cathode, and electrolyte) in a Zn/MnO2 battery are safe, abundant, and
sustainable. However, the reaction mechanism of the MnO2 cathode remains a topic
of discussion. Herein, we design a highly reversible aqueous Zn/MnO2 battery
where the binder-free MnO2 cathode was fabricated by in situ electrodeposition of
MnO2 on carbon fiber paper in mild acidic ZnSO4+MnSO4 electrolyte.
Electrochemical and structural analysis identify that the MnO2 cathode experience
a consequent H+ and Zn2+ insertion/extraction process with high reversibility and
cycling stability. To our best knowledge, it is the first report on rechargeable
aqueous batteries with a consequent ion-insertion reaction mechanism.
PMID- 28704998
TI - Polycyclic Aromatic Hydrocarbon Growth by Diradical Cycloaddition/Fragmentation.
AB - The recent theoretical and experimental investigations on the growth of
polycyclic aromatic hydrocarbons in pyrolytic environments highlight the possible
role of the 1,4-cycloaddition/fragmentation (1,4-CAF) steps in the formation of
PAH intermediates and consequently soot. The present theoretical study explores
the possibility to generalize such mechanism to reactions involving various
diradical compounds and stable multiring structures. The calculations were
performed using the uB3LYP/6-311G(d,p) method and different composite methods,
when possible, for more accurate energy estimates. First, the complex potential
energy surface for the reactions between o-benzyne and naphthalene was
investigated, including the 1,4-CAF mechanism to form anthracene and acetylene
through the dibenzobicyclo[2.2.2]octatriene intermediate. Moreover, the products
of the addition reactions to the alpha- and beta-carbons and to the ring-junction
atoms were determined. The energies for the optimized CAF structures, which
constitute the most-favorable pathway from an energetic point of view, were
calculated using CBS-QB3, G3(MP2)B3, and G3B3 methods and compared to the
corresponding values for the o-benzyne + benzene reactions. Additional
calculations were focused on the possible CAF reactions between o-benzyne and
larger multiring structures, such as anthracene, phenanthrene, pyrene, and the
four-ring PAHs. The results indicate how the energetics of such reactions is
influenced by both the size of the PAH compound and the position of the carbon
atoms involved. In the second part of the study, the energy barriers necessary to
form multiring diradicals from the corresponding radical molecules were analyzed
at a G3(MP2)B3 level of theory. Such calculations are preliminary for the
subsequent study on the CAF reactions between the different diradical
intermediates and benzene. While the size of the diradical does not affect
significantly the energy barriers, the position of the diradical site is
critical. The concerted Diels-Alder reactions between the naphthynes and
naphthalene were also studied in order to further clarify the analogies between
the reactions involving different diradicals. Based on these results, kinetic
considerations were provided based on the comparison with the simpler o-benzyne +
benzene system, although further higher-level calculations and master equation
kinetic analyses will be required to derive the general kinetic rules.
PMID- 28704999
TI - Multilayer poly(3,4-ethylenedioxythiophene)-dexamethasone and poly(3,4
ethylenedioxythiophene)-polystyrene sulfonate-carbon nanotubes coatings on glassy
carbon microelectrode arrays for controlled drug release.
AB - The authors present an electrochemically controlled, drug releasing neural
interface composed of a glassy carbon (GC) microelectrode array combined with a
multilayer poly(3,4-ethylenedioxythiophene) (PEDOT) coating. The system
integrates the high stability of the GC electrode substrate, ideal for electrical
stimulation and electrochemical detection of neurotransmitters, with the on
demand drug-releasing capabilities of PEDOT-dexamethasone compound, through a
mechanically stable interlayer of PEDOT-polystyrene sulfonate (PSS)-carbon
nanotubes (CNT). The authors demonstrate that such interlayer improves both the
mechanical and electrochemical properties of the neural interface, when compared
with a single PEDOT-dexamethasone coating. Moreover, the multilayer coating is
able to withstand 10 * 106 biphasic pulses and delamination test with negligible
change to the impedance spectra. Cross-section scanning electron microscopy
images support that the PEDOT-PSS-CNT interlayer significantly improves the
adhesion between the GC substrate and PEDOT-dexamethasone coating, showing no
discontinuities between the three well-interconnected layers. Furthermore, the
multilayer coating has superior electrochemical properties, in terms of impedance
and charge transfer capabilities as compared to a single layer of either PEDOT
coating or the GC substrate alone. The authors verified the drug releasing
capabilities of the PEDOT-dexamethasone layer when integrated into the multilayer
interface through repeated stimulation protocols in vitro, and found a
pharmacologically relevant release of dexamethasone.
PMID- 28705000
TI - Preface: pancreas adenocarcinoma.
PMID- 28705001
TI - Epidemiology of pancreatic adenocarcinoma.
AB - Pancreatic ductal adenocarcinoma is one of the most lethal cancers worldwide. The
highest incidence rates her found are in North America and in Western Europe
while lower rates in Asian Africa, with age standard incidence rates of 7.2 and
2.8 per 100,000 populations. Unfortunately the vast majority of individuals with
pancreatic cancer present with symptoms, and once symptoms develop the chance for
surgery is only about 20%. Additionally he incidence rate and mortality from
pancreatic ductal adenocarcinoma in the United States shows a very close
association suggesting that her earlier detection and treatment does little to
change the outcome from this disease. Multiple of environmental and genetic risk
factors have been implicated in the development of pancreatic ductal
adenocarcinoma. We have reviewed those risk factors we believe are most important
the development of this lethal disease. It is hoped that in the future,
identification of biomarkers unique in the development of pancreatic ductal
adenocarcinoma will be identified leading to earlier detection and a greater
frequency of potential cure of this disease.
PMID- 28705002
TI - Preclinical models of pancreatic ductal adenocarcinoma.
AB - Unlike many other cancers, pancreatic ductal adenocarcinoma (PDAC) has seen only
incremental improvement in mortality despite significant advances in our
understanding of the underlying biology. A primary obstacle to progress has been
our inability to properly model PDAC in a preclinical setting. PDAC is difficult
to study because of its genetic heterogeneity, intricate stromal
microenvironment, and complex interplay with our immune system. Finding a model
that properly accounts for all these criteria remains difficult. This review
summarizes the five primary models currently in use: human PDAC cell line, cell
line xenograft, patient derived xenograft, genetically engineered mouse model
(GEMM), and organoids. We delve into the advantages of disadvantages of each
model, while discussing how each model has been or could be used in the
preclinical setting.
PMID- 28705003
TI - Adjuvant and neoadjuvant therapy for resectable pancreatic adenocarcinoma.
AB - Resectable pancreatic adenocarcinoma presents the opportunity for cure of this
highly lethal disease by allowing complete surgical removal. However, cure rates
remain low. Adjuvant therapy following surgical resection is the standard of
care. Most data support the use of gemcitabine or 5-fluorouracil in the adjuvant
setting, and emerging data indicate gemcitabine plus capecitabine may improve
outcomes. Use of adjuvant radiation remains controversial. Ongoing clinical
studies will help better define the role of multi-agent regimens as well as
radiation in the adjuvant setting. Neoadjuvant therapy holds the promise of
allowing early control of systemic disease with increased delivery of aggressive
chemotherapy regimens. Prior studies are mostly small, single-institution trials,
making it difficult to draw conclusions. Ongoing trials across the world are
systematically testing this approach and may lead to a new therapeutic approach
to resectable pancreatic cancer.
PMID- 28705004
TI - Multimodality management of borderline resectable pancreatic adenocarcinoma.
AB - Patients with borderline resectable pancreatic adenocarcinoma have primary tumors
within the pancreas that involve the mesenteric vasculature to a limited degree.
Their tumors are nonetheless at high-risk for a microscopically positive surgical
resection margin and/or early treatment failure when pancreatectomy is performed
de novo. The optimal treatment strategy for these patients has not been
established; however, relatively favorable outcomes can be achieved with systemic
chemotherapy and radiation therapy (RT) prior to intended resection. In this
article, we discuss the modalities used to stage localized pancreatic cancer, the
concept of borderline resectable pancreatic cancer (BRPC), the rationale for the
use of preoperative therapy, and review recent publications, placing special
emphasis on the necessity of appropriate patient selection and coordinating
multimodality management to maximize outcomes.
PMID- 28705005
TI - Radiation therapy in the management of pancreatic adenocarcinoma: review of
current evidence and future opportunities.
AB - The role of radiation therapy for pancreatic cancer is rapidly evolving in every
stage of this disease. In resectable disease, there is conflicting evidence for
adjuvant therapy, but an ongoing randomized cooperative group trial is attempting
to define the role of adjuvant chemoradiation with modern systemic therapies and
radiation techniques with an emphasis on radiation quality assurance. In
borderline resectable pancreatic cancer (BRPC), there is an emerging body of
literature demonstrating the success of neoadjuvant stereotactic body radiation
therapy (SBRT) and a randomized cooperative group trial is actively accruing. For
locally advanced pancreatic cancer (LAPC), the recent publication of the LAP07
trial has called into question the role of conventional chemoradiation, but there
is a growing experience utilizing SBRT for this patient group. Finally, in the
era of immuno-oncology, there may be a new role for radiation therapy in
combination with systemic immune therapy to stimulate antigen release and
abscopal responses, thus benefitting even patients with metastatic pancreatic
cancer.
PMID- 28705006
TI - Best practices for the treatment of metastatic pancreatic adenocarcinoma: the
therapeutic landscape in 2017.
AB - The vast majority of patients diagnosed with pancreatic adenocarcinoma have
inoperable, most commonly metastatic, disease at the time of initial
presentation, at which point systemic therapy becomes the mainstay of treatment.
Although survival rates remain very poor in this clinical setting, patients
currently have a greater number of therapeutic options available to them than
ever before, and consequently individuals are more frequently able to be
sequenced through multiple lines of treatment. In this review, we will provide an
overview of the current treatment landscape for metastatic pancreatic cancer in
2017, focusing on best practices and the various factors that should be
considered in selecting the most appropriate regimen for a given individual.
Options for front-line therapy include both infusional 5-fluorouracil,
leucovorin, irinotecan, oxaliplatin (FOLFIRINOX) and the combination of
gemcitabine plus nab-paclitaxel; however, how to choose between these two
regimens can sometimes pose a challenging problem, and some patients may not be
suitable candidates for either. For patients who are robust enough to receive
second-line therapy (and beyond), the selection of treatment depends in part on
their prior treatment exposure; newer drugs such as nanoliposomal irinotecan (nal
IRI) (in combination with infusional 5-fluorouracil and leucovorin) are now
approved by the United States Food and Drug Administration (FDA) specifically for
use following disease progression on first-line gemcitabine-based therapy.
Despite these welcome advances in standard of care treatment, patients should
still be encouraged to participate in clinical trials whenever possible.
PMID- 28705007
TI - Pancreas adenocarcinoma: novel therapeutics.
AB - Pancreatic ductal adenocarcinoma (PDAC) is the third highest cause of cancer
related deaths in the US, and is projected to be second only to non-small cell
lung cancer (NSCLC) by the 2020s. Current therapies have a modest impact on
survival and median overall survival (mOS) across all stages of disease remains
under a year. Over the last decade, however, great strides have been made in the
understanding of PDAC pathobiology including the role of the tumor
microenvironment (TME), DNA damage repair and mechanism of immunosuppression.
Exciting novel therapeutics are in clinical development targeting the TME to
increase cytotoxic drug delivery, decrease immunosuppressive cell presence and
attack cancer stem cells (CSCs). Immune checkpoint inhibitors, cancer vaccines
and other immunotherapies are actively being studied and novel combinations of
targeted agents are being pursued. There is a sense of optimism in the oncology
community that these scientific advances will translate into improved outcomes
for patients with PDAC in the proximate future. In this review, we examine
various novel therapeutics under clinical development with a focus on stromal
disrupting agents, immunotherapeutics and DNA damage repair strategies.
PMID- 28705008
TI - Rational combinations of immunotherapy for pancreatic ductal adenocarcinoma.
AB - The complex interaction between the immune system, the tumor and the
microenvironment in pancreatic ductal adenocarcinoma (PDA) leads to the
resistance of PDA to immunotherapy. To overcome this resistance, combination
immunotherapy is being proposed. However, rational combinations that target
multiple aspects of the complex anti-tumor immune response are warranted. Novel
clinical trials will investigate and optimize the combination immunotherapy for
PDA.
PMID- 28705009
TI - Palliative care and advance care planning for pancreas and other cancers.
AB - The principles of palliative care are fundamental to support and treat the
physical, mental, and psychosocial health of patients living with pancreatic
cancer. In addition to its proven advantages to help manage disease-related
symptoms, improve accurate illness understanding, and enhance the quality of life
and survival outcomes for patients with advanced disease, the inclusion of
palliative care principles (whether by a specialist or by the primary oncology
team) with standard oncologic care strengthens timely and quality advance care
planning (ACP). The primary objective of this review article is to underscore the
significant value of palliative care integration and ACP in oncology, including
but not limited to care at the end of life, with a particular focus on its
relevance to patients with advanced pancreatic cancer.
PMID- 28705010
TI - Isocitrate dehydrogenase mutation as a therapeutic target in gliomas.
AB - Isocitrate dehydrogenases (IDH) are important enzymes that catalyze the oxidative
decarboxylation of isocitrate to alpha-ketoglutarate (alpha-KG), producing NADPH
in the process. More than 80% of low-grade gliomas and secondary glioblastoma
(GBM) harbor an IDH mutation. IDH mutations involve the catalytic pocket of the
enzyme and lead to a neomorphic ability to produce 2-hydroxyglutarate (2HG) while
oxidizing NADPH to NADP+. 2HG is considered as an 'oncometabolite' which is
thought to be responsible for many, if not all, biologic effects of IDH
mutations. 2HG accumulation competitively inhibits alpha-KG-dependent
dioxygenases, including histone lysine demethylases and DNA demethylases,
resulting in a hypermethylation phenotype with alterations in cellular epigenetic
status as well as a block in cellular differentiation. IDH mutations have been
suggested as an important early event in tumorigenesis, however it remains
unclear whether IDH mutation by itself causes cancer or if it requires other
oncogenic events to initiate tumorigenesis. Significant efforts have been made to
better understand the mechanisms of IDH mutations in tumor initiation and
progression, and to develop targeted therapies for IDH-mutated tumors. This
review provides an overview of the function of mutant IDH, and the current
understanding of the role IDH mutations play in gliomagenesis. In addition,
several potential therapeutic strategies for IDH-mutant gliomas, including mutant
IDH inhibitors which have entered clinical evaluation in glioma patients, will be
discussed.
PMID- 28705011
TI - The experiences and beliefs of patients with complex regional pain syndrome: An
exploratory survey study.
AB - Objectives To determine the beliefs and describe the health care experiences of
patients with complex regional pain syndrome. Methods A survey tool for patients
with complex regional pain syndrome was designed for this study. The survey tool
collected self-reported measures associated with pain, disability, health care
experiences, education, beliefs, and treatments. Results Thirty-one patients
attending physical therapy for complex regional pain syndrome (mean age 40.48;
female n = 20) completed the survey. Patients with presented with high levels of
pain and disability and reported various changes associated with altered
neuroplasticity such as confused body part recognition, left/right
discrimination, neglect, and spreading pain. The patients' experiences with
diagnostic testing and interventions are not in line with the current pain
science research and/or evidence-based practice. Overall, patients are ill
informed, confused, and receive conflicting information. Discussion The suffering
associated with complex regional pain syndrome is real, as told by patients. This
suffering coincides with a lack of consensus by health care providers and
conflicting information on complex regional pain syndrome. Overall, patient
experiences show health care providers are not up to date with the current best
evidence regarding complex regional pain syndrome.
PMID- 28705012
TI - The Relationship Between Core Members' Social Capital and Perceived and
Externally Evaluated Prestige and Cooperation Among HIV/AIDS-Related Civil
Society Organizations in China.
AB - The purpose of this study was to investigate whether the core members' social
capital was associated with individually perceived and externally evaluated
prestige and cooperation among the HIV/AIDS-related civil society organizations
(CSOs). To accomplish this, a cross-sectional study using multistage sampling was
carried out in eight provinces of China. Data were collected from the 327 core
members via questionnaires and self-evaluated performance of the respondents were
evaluated and measured. The interviews were conducted with all core members and
the supervisory staff of the local Centers for Disease Control and Prevention.
Multivariate logistic regression analysis indicated that social support (adjusted
odds ratio [a OR] = 1.87) and organizational commitment (a OR = 1.57) were
significantly associated with a higher odds of prestige performance in self
evaluation. Furthermore, social support (a OR = 1.65), trust (a OR = 1.33), and
organizational commitment (a OR = 1.52) were significantly correlated with
cooperation performance. Trust was positively associated with the cooperation
performance on external evaluation. These findings may provide a new perspective
on challenges that the CSOs face in response to a growing HIV/AIDS epidemic in
China. Social capital may increase performance and accelerate organizational
growth, ultimately improving HIV/AIDS prevention and care.
PMID- 28705013
TI - Cognitive Fluctuations and Cognitive Test Performance Among Institutionalized
Persons With Dementia.
AB - OBJECTIVE: To examine the nature and frequency of cognitive fluctuations (CFs)
among institutionalized persons with dementia. METHOD: A clinical interview and a
medical chart review were conducted, and 55 patients were assigned a specific
dementia diagnosis. The Severe Impairment Battery (SIB) was administered to
assess cognitive function, and the Dementia Cognitive Fluctuation Scale (DCFS)
was administered to each patient's primary nurse to determine the presence and
severity of CFs. RESULTS: A simple linear regression model was conducted with
DCFS as the predictor variable and SIB total score as the dependent variable. The
overall model was significant, suggesting that score on the DCFS significantly
predicted SIB total score. Additionally, greater severity of CFs predicted poorer
performance in the areas of orientation, language, and praxis. CONCLUSIONS:
Results suggest that CFs exert a clinically significant influence over patients'
cognitive abilities and should be considered as a source of excess disability.
PMID- 28705014
TI - Mutation in the RRM2 domain of TDP-43 in Amyotrophic Lateral Sclerosis with rapid
progression associated with ubiquitin positive aggregates in cultured motor
neurons.
AB - Mutations in the TAR-DNA Binding Protein-43 (TDP-43) encoding the TARDBP gene are
present in amyotrophic lateral sclerosis (ALS). TDP-43 is the major component of
ubiquitin-positive inclusions in motor neurons in ALS patients. We report here a
novel heterozygous missense mutation in TARDBP in an ALS patient presenting a
rapid form of ALS. This mutation p.N259S is located within the RNA recognition
motif 2 (RRM2) in very close proximity with nucleotides in RNA. It is the first
time a mutation was reported in this RRM2 domain of TDP-43. Expression of TDP
43N259S in neuronal cells NSC-34 and in primary cultures of motor neurons was
associated with cytoplasmic TDP-43/ubiquitin positive inclusions. Our findings
identified for the first time a mutation in ALS in the RRM2 domain of TDP-43,
reinforcing the link between this RNA-binding protein, perturbations in RNA
metabolism, disruption in protein homeostasis and ALS.
PMID- 28705015
TI - Decision-making on shared sanitation in the informal settlements of Kisumu,
Kenya.
AB - Unlike most quantitative studies that investigate decision-making on investing in
sanitation, this study adopted a qualitative approach to investigate decision
making on shared sanitation in the informal settlements of Kisumu city, in Kenya.
Using a grounded theory approach, landlords and tenants were interviewed to
identify sanitation decisions, individuals involved in decision-making and
factors influencing decision-making. The results indicate that the main
sanitation decisions are on investment, emptying, repair and cleaning. Landlords
make investment, emptying and repair decisions, while tenants make cleaning
decisions. Absentee landlords are less involved in most decision-making compared
to live-in landlords, who rarely consult tenants in decision-making. Tenants make
decisions after consultations with a third party and often collectively with
other tenants. Sanitation interventions in informal settlements should thus,
target landlords and tenants, with investment efforts being directed at landlords
and maintenance efforts at tenants.
PMID- 28705016
TI - Education and social inclusion of people with disabilities in five countries in
West Africa: a literature review.
AB - PURPOSE: An estimated 1 billion people worldwide live with some form of
disability. With the adoption of the Sustainable Development Goals and the "Leave
no one behind" agenda, there is a global momentum to ensure that disadvantaged
groups, not least people with disabilities, are included and accounted for, in
mainstream development efforts. However, in many low-income settings little is
known about disability and the policies and programs in place to improve the
lives of those affected. METHOD: This literature review describes the extent and
quality of published and unpublished literature on education and social inclusion
of people with disabilities in five West African countries: Cameroon, Liberia,
Mali, Sierra Leone and Senegal. RESULTS: Fifty-four unique documents met
inclusion criteria of the review and described related policy and legislation;
national and international stakeholders; intervention programs and primary
research related to disability and inclusion. The majority of documents were from
Sierra Leone (19); and four described more than one country. Primary research
included mainly qualitative studies and cross-sectional surveys; 33 sources were
critically appraised with the majority being attributed unclear risk of bias
(20). CONCLUSIONS: The findings call for (i) standardized tools for monitoring
the implementation of programs and policies at national level; (ii) improved
stakeholder coordination mechanisms; (iii) development and adoption of
coordinated approaches to measuring disability and social exclusion; (iv)
rigorous evaluations of the effectiveness of disability programs and (v)
disaggregation of routine data by disability. Implication for Rehabilitation
There is a need for standardized tools for monitoring the implementation of
programs and policies at national level. Countries that have not yet ratified the
UNCRPD or the protocol should be supported to do so. Stakeholder coordination
mechanisms need to be improved. Improved coordination between stakeholders
involved in disability at the country level could help improve the quality of
services delivered. Development and adoption of coordinated approaches is key to
measuring disability and social exclusion. There are few, if any, rigorous
evaluation of the effectiveness of disability-specific evaluations in the five
countries. There is a need for disaggregation of routine data from development
programs by disability to inform implementation.
PMID- 28705017
TI - Impact of geometry optimization methods on QSAR modelling: A case study for
predicting human serum albumin binding affinity.
AB - Quantitative structure-activity relationship (QSAR) modelling is a major tool
employed in the prediction of various endpoints. However, current QSAR literature
is missing a full understanding of the impact of quantum chemical calculation
methods on the estimation of molecular descriptors and model performance. Here,
we provide a comprehensive analysis of the quantitative effects of different
geometry optimization methods (semi-empirical, ab initio Hartee-Fock and density
functional theory) on the molecular descriptors. Using experimental binding
affinity to human serum albumin (HSA) data, we comparatively investigated the
influence of employing descriptors derived from three calculation methods on the
QSAR models. We propose a 4-descriptor QSAR model in line with the OECD
validation principles for the prediction of drug binding affinity to HSA (log
KHSA) as a potential tool for drug development. We also confirm the prediction
capability of the proposed model on a heterogeneous external set of chemicals.
Furthermore, we recommend an activity-independent rational approach for the
selection of geometry optimization method for an improved QSAR model development.
PMID- 28705018
TI - Secondary pneumothorax induced by metastatic angiosarcoma.
PMID- 28705019
TI - A rare case of pediatric primary cardiac tumor in a patient with Down syndrome.
AB - Although hematological malignancies are a known complication of Down syndrome,
few reports have described cases involving solid tumors. We describe the case of
a 3-year-old Down syndrome girl with a primary solid cardiac tumor. Outpatient
echocardiography after intracardiac repair of a ventricular septal defect at 6
months of age revealed a highly mobile pedunculated mass (8 * 9 mm) on the free
wall of the right atrium. Due to potential incarceration of the mass in the
tricuspid orifice, it was excised under extracorporeal circulation and cardiac
arrest. Macroscopically, the tumor closely resembled a papillary fibroelastoma,
although histopathological tests were inconclusive.
PMID- 28705020
TI - Differential Item Functioning of the Full and Brief Wisconsin Schizotypy Scales
in Asian, White, Hispanic, and Multiethnic Samples and Between Sexes.
AB - The Wisconsin Schizotypy Scales, including their brief versions, are among the
most commonly used self-report measures of schizotypy. Although they have been
used extensively in many ethnic groups, few studies have examined their
differential item functioning (DIF) across groups. The current study included
1,056 Asian, 408 White, 476 Multiethnic, and 372 Hispanic undergraduates.
Unidimensional models of the brief Magical Ideation Scale and Perceptual
Aberration Scales fit the data well. For both scales, global tests of measurement
invariance provided mixed evidence, but few of the items displayed DIF across
ethnicities or between sexes within a multiple indicator multiple causes model.
For the full versions of the scales and the brief Revised Social Anhedonia Scale,
multiple indicator multiple causes models within an exploratory structural
equation modeling framework found that few of the items had DIF. These findings
suggest that some of the items may have different psychometric properties across
groups, but most items do not.
PMID- 28705021
TI - Atorvastatin-loaded micelles with bone-targeted ligand for the treatment of
osteoporosis.
AB - Osteoporosis is a common bone disorder where the declined bone mass is far more
than normal physiological status and usually associated with enhanced fracture
risk, reduced bone strength and even deteriorated quality of life. Recent studies
showed that statins could exert beneficial effects on bones via promoting
osteoblastic activity mediated by increased expression of bone morphogenetic
protein 2 and also by suppressing osteoclast proliferation. In this study, we
developed atorvastatin-loaded tetracycline-poly (ethylene glycol)-poly(lactic-co
glycolic acid) (TC-PEG-PLGA/ATO) micelles for the targeted treatment of
osteoporosis. The TC-PEG-PLGA was synthesized under the action of coupling
reagents and then ATO was encapsulated through solvent diffusion method with
encapsulation efficiency and drug loading of 89.32 +/- 2.48% and 8.20 +/- 0.53%,
respectively. The release of ATO from micelles could be maintained for more than
48 h in pH 7.4 PBS. Pharmacokinetic results further demonstrated that TC-PEG-PLGA
micelles could effectively shield ATO leakage from micelles and prolong their
circulation time. Benefiting from TC specifically binding to hydroxyapatite
(HAp), TC-PEG-PLGA/ATO micelles exerted good bone-targeted ability, as
demonstrated by in vitro HAp affinity assay and biodistribution. Pharmacodynamic
studies showed that TC-PEG-PLGA/ATO micelles could effectively improve bone
mineral density and bone mechanical strength in osteoporotic rats. These results
suggest that TC-PEG-PLGA/ATO micelles hold significant promise for the targeted
treatment of osteoporosis.
PMID- 28705022
TI - Evaluation of dose and outcomes for pediatric vilazodone ingestions.
AB - BACKGROUND: Selective serotonin reuptake inhibitor (SSRI) exposures among
children younger than 6 years of age are generally well tolerated. Vilazodone is
an SSRI with partial agonism at the 5-HT1A receptor with demonstrated clinical
efficacy for depression whose off-label usage is likely to increase. Recent
evidence suggests that unintentional ingestion of vilazodone in children under 6
years old is associated with more severe clinical effects than other SSRIs. We
chose to evaluate dose and outcomes for pediatric vilazodone ingestions. METHODS:
A retrospective analysis of single-substance exposures associated with vilazodone
among children younger than 6 years of age from 2011 through 2016 was conducted
using data from the National Poison Data System. RESULTS: During 2011-2016, 753
vilazodone ingestions among children <6 years old were reported to US poison
control centers. A near majority (49.0%, n = 369) experienced one or more
clinical effects. The dose ingested was reported for 596 children (79%). The
median dose associated with major effects was 50.0mg (Mean: 106.0) compared with
40.0mg (Mean 81.1) for moderate effects. Half (50.0%) of children with a major
effect and 54.0% with a moderate effect ingested <=40 mg of vilazodone. As the
dose of vilazodone ingested increased, the proportions of exposures admitted to a
healthcare facility (HCF) (p < .001) and with serious outcomes (p < .001) both
increased. Children <=2 years had higher proportions of HCF admission (33.8% vs
23.1%) and serious outcomes (27.0% vs 17.7%) than children 3-5 years of age.
Clinical effects, such as coma, seizures, ataxia, and hallucinations/delusions,
were observed among children ingesting doses of vilazodone as low as 10 mg.
CONCLUSIONS: Exposure to vilazodone poses a unique and potentially serious threat
to children <6 years of age. Children in this age group who are exposed to
vilazodone should be evaluated promptly in a clinical setting. Off-label use of
vilazodone in children under 6 years should be discouraged until further research
is conducted regarding its safety in this population.
PMID- 28705023
TI - Helping Hospitals Improve Patient Centeredness: Assessing the Impact of Feedback
Following a Best Practices Workshop.
AB - Regularly reported patient surveys are an important dimension of hospital quality
management. This study investigates whether providing hospital staff with interim
feedback on patient survey results following a best practices workshop can help
hospitals improve patient centeredness. Standardized surveys with consecutive
patient samples were administered in accredited breast cancer center (BCC)
hospitals in one German state (18 million inhabitants), over a 6-month period, in
2012. Two studies were conducted by applying a combination of regression point
displacement (RPD) and interrupted time series (ITS) designs. In Study 1, 2 of
the 27 hospitals that had previously participated in a best practices workshop to
discuss patient-centeredness issues were randomly chosen and were provided
interim feedback of patient survey results and workshop minutes. In Study 2, 4
randomly chosen hospitals of 32 that had not participated in the workshop also
received interim feedback but no workshop minutes. Control hospitals in both
studies neither received feedback nor workshop minutes. The impact of interim
feedback was evaluated by applying graphical assessments and multiple regression
analyses. Both graphical assessments (locally weighted scatterplot smoothing
(LOESS) lines, RPD plots) suggested an effect of interim feedback. Multiple
regression results did not unambiguously support these findings. The suggested
design approach may prove particularly useful to assess effects in pilot studies,
when resources are not available to conduct a randomized study or when its
conduct is contingent on initial, positive evidence.
PMID- 28705024
TI - MEDI 4736 (durvalumab) in non-small cell lung cancer.
AB - INTRODUCTION: Immune checkpoint inhibitors (ICI) are now a therapeutic option for
advanced non-small cell lung cancer (NSCLC) patients. ICI, such as the PD-1
inhibitors nivolumab and pembrolizumab and the PD-L1 inhibitor atezolizumab, have
already been marketed for the treatment of pretreated patients with advanced
NSCLC. Other notable PD-L1 inhibitors under development include avelumab and
durvalumab. Areas covered: This article reviews literature on durvalumab
development, from the preclinical data to the results of phase III clinical
trials, whether published or presented at international scientific conferences.
Ongoing clinical trials were also reviewed. Expert opinion: Early phase trials of
durvalumab monotherapy (and in combination) have demonstrated activity in
advanced NSCLC patients and it has demonstrated a good safety profile. The
authors believe that durvalumab will likely play an important role in future
treatment strategies for NSCLC. The PACIFIC trial assessing durvalumab after
standard chemoradiotherapy for locally advanced NSCLC has already met its primary
endpoint and the potential of durvalumab will be reinforced if phase III
randomized studies of first-line (MYSTIC trial) and second or subsequent (ARCTIC
trial) lines of therapy demonstrate superiority over the current standard of
care.
PMID- 28705025
TI - Improving the sensitivity and specificity of a bioanalytical assay for the
measurement of certolizumab pegol.
AB - AIM: In order to evaluate placental transfer of certolizumab pegol (CZP), a more
sensitive and selective bioanalytical assay was required to accurately measure
low CZP concentrations in infant and umbilical cord blood. Results & methodology:
A new electrochemiluminescence immunoassay was developed to measure CZP levels in
human plasma. Validation experiments demonstrated improved selectivity (no matrix
interference observed) and a detection range of 0.032-5.0 MUg/ml. Accuracy and
precision met acceptance criteria (mean total error <=20.8%). Dilution linearity
and sample stability were acceptable and sufficient to support the method.
CONCLUSION: The electrochemiluminescence immunoassay was validated for measuring
low CZP concentrations in human plasma. The method demonstrated a more than
tenfold increase in sensitivity compared with previous assays, and improved
selectivity for intact CZP.
PMID- 28705026
TI - The Association Between Peer and Self-Assessments and Professionalism Lapses
Among Medical Students.
AB - Peer and self-assessments are widely used to assess professionalism during
medical school as part of a multisource feedback model. The purpose of this study
was to examine the associations between peer and self-assessments and
professionalism lapses at a large medical school. A retrospective case-control
study design was used to compare peer and self-assessment scores from Years 1 to
3 of medical school for students who had been cited for professionalism lapses
during medical school (case group; n = 78) with those of a randomly selected
control group ( n = 230). Students in the case group had significantly lower peer
assessment scores than students in the control group during all 3 years. Year 3
peer assessment scores showed the greatest difference (cases = 7.81 +/- 0.65,
controls = 8.22 +/- 0.34, p < .01). Students with lower peer assessment scores
were also significantly more likely to have been cited for a professionalism
lapse (odds ratio = 6.25, 95% CI [3.13, 11.11], p < .01). This study reinforces
the value of peer assessments of professionalism, which may be useful to help
identify students who may be at risk for professionalism lapses during medical
school.
PMID- 28705027
TI - Tensor algebra-based geometric methodology to codify central chirality on organic
molecules.
AB - A novel mathematical procedure to codify chiral features of organic molecules in
the QuBiLS-MIDAS framework is introduced. This procedure constitutes a
generalization to that commonly used to date, where the values 1 and -1
(correction factor) are employed to weight the molecular vectors when each atom
is labelled as R (rectus) or S (sinister) according to the Cahn-Ingold-Prelog
rules. Therefore, values in the range [Formula: see text] with steps equal to
0.25 may be accounted for. The atoms labelled R or S can have negative and
positive values assigned (e.g. -3 for an R atom and 1 for an S atom, or vice
versa), opposed values (e.g. -3 for an R atom and 3 for an S atom, or vice
versa), positive values (e.g. 3 for an R atom and 1 for an S atom) or negative
values (e.g. -3 for an R atom and -1 for an S atom). These proposed Chiral QuBiLS
MIDAS 3D-MDs are real numbers, non-symmetric and reduced to 'classical' (non
chiral) QuBiLS-MIDAS 3D-MDs when symmetry is not codified (correction factor
equal to zero). In this report, only the factors with opposed values were
considered with the purpose of demonstrating the feasibility of this proposal.
From QSAR modelling carried out on four chemical datasets (Cramer's steroids,
fenoterol stereoisomer derivatives, N-alkylated 3-(3-hydroxyphenyl)-piperidines,
and perindoprilat stereoisomers), it was demonstrated that the use of several
correction factors contributes to the building of models with greater robustness
and predictive ability than those reported in the literature, as well as with
respect to the models exclusively developed with QuBiLS-MIDAS 3D-MDs based on the
factor 1 | -1. In conclusion, it can be stated that this novel strategy
constitutes a suitable alternative to computed chirality-based descriptors,
contributing to the development of good models to predict properties depending on
symmetry.
PMID- 28705028
TI - Development of a Computer Adaptive Test for Depression Based on the Dutch-Flemish
Version of the PROMIS Item Bank.
AB - We developed a Dutch-Flemish version of the patient-reported outcomes measurement
information system (PROMIS) adult V1.0 item bank for depression as input for
computerized adaptive testing (CAT). As item bank, we used the Dutch-Flemish
translation of the original PROMIS item bank (28 items) and additionally
translated 28 U.S. depression items that failed to make the final U.S. item bank.
Through psychometric analysis of a combined clinical and general population
sample ( N = 2,010), 8 added items were removed. With the final item bank, we
performed several CAT simulations to assess the efficiency of the extended (48
items) and the original item bank (28 items), using various stopping rules. Both
item banks resulted in highly efficient and precise measurement of depression and
showed high similarity between the CAT simulation scores and the full item bank
scores. We discuss the implications of using each item bank and stopping rule for
further CAT development.
PMID- 28705029
TI - Bosnian study of APOE distribution (BOSAD): a comparison with other European
populations.
AB - BACKGROUND: The epsilon2, epsilon3 and epsilon4 alleles of APOE gene have been
associated with several diseases in different populations. Data on the frequency
of alleles are used in both a clinical and evolutionary context. Although the
data on frequency of these alleles are numerous, there are no reports for the
population of Bosnia and Herzegovina. AIM: To estimate the frequency of APOE
alleles in a healthy Bosnian population and compare it to data for other European
populations. SUBJECTS AND METHODS: Overall, 170 unrelated Bosnian subjects (108
female and 62 male), aged 53.0 (+/-5.0) years were included in this study.
Genotypes were determined by real-time PCR. RESULTS: In our group the prevalence
of heterozygotes E2/E3, E2/E4 and E3/E4 was 20.6%, 3.5% and 12.9%, respectively,
while the prevalence of homozygotes E2/E2, E3/E3, E4/E4 was 0.6%, 61.2% and 1.2%,
respectively, with a mean frequency of epsilon2, epsilon3 and epsilon4 alleles of
12.6%, 78.0% and 9.4%, respectively. CONCLUSIONS: In studied European populations
we observed a linear, gradually increasing trend in the frequency of epsilon4
allele from South to North (Pearson's test 0,7656, p value <0.00001), and the
Bosnian population fits into this pattern perfectly.
PMID- 28705030
TI - College Students' Responses to Emotional Anti-Alcohol Abuse Media Messages:
Should We Scare or Amuse Them?
AB - This study examined college students' responses to emotional anti-alcohol abuse
media messages (i.e., fear vs. humor appeal) aimed at discouraging heavy/binge
drinking. An experiment was conducted with 94 college students. As expected,
college students generally expressed higher levels of interest in anti-alcohol
abuse media messages when watching fear appeal than those watching humor appeal.
However, college binge drinkers who watched the fear appeal reported lower levels
of readiness to change their drinking behavior than those who watched the humor
appeal. This pattern was the opposite among college nonbinge drinkers, in that
college nonbinge drinkers were more likely to say they would change their
drinking behaviors when exposed to fear appeal than those who were exposed to
humor appeal or those who did not watch any media messages. Conventional fear
appeal to scare college binge drinkers seems ineffective and even
counterproductive while humor appeal, if well designed, could offer alternative
ways to communicate with college binge drinkers.
PMID- 28705031
TI - Barium exposure increases the risk of congenital heart defects occurrence in
offspring.
AB - CONTEXT: Several studies have investigated the association between heavy metal
exposure and congenital heart defects (CHDs). However, there are limited data
regarding the relationship between barium exposure and the occurrence of CHDs.
The objective of this study was to analyze the association between barium
exposure in mothers and the risk of CHD in offspring. MATERIALS AND METHODS: We
developed a case-control study with 399 cases and 490 controls with normal live
births in China. The concentrations of barium in hair of pregnant woman and fetal
placenta were measured. We used a logistic regression analysis to explore the
association between barium exposure and the risk of CHD. RESULTS: Logistic
regression analysis indicated that the median concentration of barium in maternal
hair in the CHD group was 4.180 ng/mg (adjusted odds ratio [aOR], 1.230; 95%
confidence interval [CI], 1.146-1.321; p < .001), which was significantly higher
than that in the control group (2.740 ng/mg). Furthermore, the median
concentration of barium in fetal placental tissue in the CHD group was 0.617
ng/mg, while that in the control group was 0.447 ng/mg (aOR, 1.392; 95% CI, 1.074
1.659; p = .003). Significant differences in the concentration of barium in hair
were also found between the different CHD subtypes and the controls. These
differences were found in cases with septal defects (p < .001), conotruncal
defects (p < .001), right ventricular outflow track obstruction (p < .001), left
ventricular outflow track obstruction (p < .001), and anomalous pulmonary venous
return (p = .010). Significantly different barium concentrations in fetal tissue
were only found in cases with septal defects (p = .010). CONCLUSIONS: Maternal
barium exposure was dose-dependently related to the risk of CHD in the offspring.
Our findings suggest that the occurrence of some subtypes of CHD is associated
with barium exposure.
PMID- 28705032
TI - Response to Commentary: Investigating the Reliability and Factor Structure of
Kalichman's "Survey 2: Research Misconduct" Questionnaire: A Post Hoc Analysis
Among Biomedical Doctoral Students in Scandinavia.
PMID- 28705033
TI - Differences in performance in CAMCOG-R domains between old and oldest old
patients with Alzheimer's disease.
AB - The purpose of this study is to evaluate the neuropsychological performance in a
>=90-year-old population with Alzheimer disease (AD) in comparison with younger
elderly patients. We retrospectively studied all patients with AD attended in a
specialized clinic between 1999 and 2011. Age, sex, educational level, and
sensory loss data were collected. Neuropsychological evaluation included Mini
Mental State Examination and Global Deterioration Scale. We used the eight
Cambridge Cognitive Assessment (CAMCOG-R) domains to evaluate and compare the
neuropsychological performance in the younger than 90 years old (<90) and older
than 90 years old (>=90) groups. We selected 2931 patients, 2897 <90 (98.83%) and
34 >=90 years old (1.17%). The >=90 group had significant lower punctuations in
memory, praxis, and abstract thinking CAMOCG-R domains with 1.49, 0.75, and 0.58
less points, respectively, (p < 0.05). Neuropsychological characteristics of
cognitive decline seem to be different in >=90 compared to <90 years old
patients. According to age, the biggest differences in the CAMCOG-R performance
are in the memory, praxis, and abstract thinking domains.
PMID- 28705034
TI - Biodistribution and clearance of magnetoelectric nanoparticles for nanomedical
applications using energy dispersive spectroscopy.
AB - AIM: The biodistribution and clearance of magnetoelectric nanoparticles (MENs) in
a mouse model was studied through electron energy dispersive spectroscopy.
MATERIALS & METHODS: This approach allows for detection of nanoparticles (NPs) in
tissues with the spatial resolution of scanning electron microscopy, does not
require any tissue-sensitive staining and is not limited to MENs. RESULTS: The
size-dependent biodistribution of intravenously administrated MENs was measured
in vital organs such as the kidneys, liver, spleen, lungs and brain at four
different postinjection times including 1 day, 1 week, 4 and 8 weeks,
respectively. CONCLUSION: The smallest NPs, 10-nm MENs, were cleared relatively
rapidly and uniformly across the organs, while the clearance of the larger NPs,
100- and 600-nm MENs, was highly nonlinear with time and nonuniform across the
organs.
PMID- 28705035
TI - The association between ABO blood types and venous thromboembolism in individuals
with a positive antiphospholipid profile is varied by sex.
AB - Objectives Although non-O blood type is an established risk factor for venous
thromboembolism in the general population, the impact of ABO blood type (ABO) on
venous thromboembolism risk in individuals with persistent antiphospholipid
antibodies (aPL) has not been studied. We sought to investigate the relationship
between ABO and venous thromboembolism in aPL-positive individuals. We also
sought to explore potential interactions between ABO and sex or race to determine
whether ABO contributes to race or sex differences with respect to the
development of venous thromboembolism. Methods We identified all patients over 18
years old followed at a tertiary medical center between January 2000 and January
2015 with serological aPL criteria and ABO data. Episodes of venous
thromboembolism were recorded. Logistic regression models were fitted to estimate
odds ratios (ORs) of venous thromboembolism for non-O (A, B, or AB blood types)
versus O blood type. Results There were 226 patients included in the final
analysis, of whom 75 (33%) had reported venous thromboembolism. In the overall
sample, there was a non-significant difference between venous thromboembolism in
patients with non-O blood type compared to O blood type (OR 1.64, 95% confidence
interval (CI) 0.94, 2.88; P = 0.08). Men with non-O blood type had a
significantly higher risk of venous thromboembolism as compared to men with O
type blood (OR 4.94, 95% CI 1.37, 17.85; P = 0.02), but there was no significant
association between ABO and venous thromboembolism among women (OR 0.96, 95% CI
0.50, 1.83; P = 0.52). Conclusions Non-O blood type may be an under-recognized
risk factor for venous thromboembolism among men with persistent aPL antibodies,
whereas the risk associated with non-O blood type seen in the general population
may be attenuated in aPL-positive women.
PMID- 28705036
TI - Pregnancy outcomes among women with systemic lupus erythematosus: a retrospective
cohort study from Thailand.
AB - Objective The objective of this paper is to compare adverse pregnancy outcomes
between normal pregnancies and pregnancies with systemic lupus erythematosus
(SLE), particularly focusing on uncomplicated SLE with remission. Methods A
retrospective cohort study was conducted by accessing the Maternal-Fetal Medicine
(MFM) Unit database and the full medical records of the women. The records of
singleton pregnancies with SLE and no underlying disease were assigned as the
study group and their medical records were reviewed. The low-risk pregnancies
were randomly selected as the controls. The adverse pregnancy outcomes were
compared between the control group vs women with SLE, control group vs
uncomplicated SLE, and between the subgroups within the study group. Results Of
28,003 births during the study period, 1400 controls and 140 pregnancies with SLE
were compared. The rates of fetal loss, preterm birth, small-for-date, low birth
weight and preeclampsia were significantly higher in the study groups with a
relative risk of 5.6 (95% CI: 2.9-10.9), 3.2 (95% CI: 2.5-4.1), 3.5 (95% CI: 2.4
4.9), 4.2 (95% CI: 3.4-5.3) and 2.9 (95% CI: 1.9-4.4), respectively. The
increased rates of most adverse outcomes were still noted even in the cases of
uncomplicated SLE. Among women with SLE, lupus nephritis, chronic hypertension,
antiphospholipid syndrome, active disease at the onset of pregnancies, and
proteinuria were significantly associated with such outcomes. Conclusions
Pregnancies with SLE, even in uncomplicated cases with remission, increase the
risk of poor pregnancy outcomes. The presence of lupus nephritis, chronic
hypertension, antiphospholipid syndrome, active disease at the onset of
pregnancies, and proteinuria were significantly associated with such outcomes.
PMID- 28705037
TI - Saffron and its derivatives, crocin, crocetin and safranal: a patent review.
AB - INTRODUCTION: Saffron and its main components have traditionally been used as
pharmaceutical agents. Current experimental research projects have also exhibited
their applications in a wide spectrum of disorder treatments. Area covered: This
review covers the demonstrated findings and patents on therapeutic/pharmaceutical
properties of saffron and related derivatives, since 2000 to bold their
outstanding merit on human health. An extensive literature review was performed
in USP Patent, Patentscope, Espacenet and Google Patent in the field of CNS,
cardiovascular, urogenital, dermatological and inflammatory disorders. Expert
opinion: The growing body of patents showed the value of saffron and the
respective crucial components alone or in combination with the other raw
materials, herbal extracts, to apply in various therapeutic/pharmaceutical areas.
They could be engaged as an adjuvant treatment in phototherapy, cancer,
cardiovascular and neurodegenerative diseases and hypoxia-induced dangerous
conditions. However, the application of these components in the clinic has been
limited to very few drugs yet. This might be due poor clinical trials data.
According the human trend toward the use of plant-derived compounds instead of
medicines derived from chemical substances, special attention must be focused to
link the worth of saffron, herbal medicine of third millennium, from basic
sciences to patients' bed.
PMID- 28705038
TI - Correction to: Diamantopoulos et al., Evaluation of the performance of tuberculin
skin test and Quantiferon-TB gold in tube test in patients with hematologic
malignancies.
PMID- 28705039
TI - The Associations of Complicated Grief, Depression, Posttraumatic Growth, and Hope
Among Bereaved Youth.
AB - Research on the association between complicated grief (CG), hope, and
posttraumatic growth (PTG) among bereaved youth is limited. Measures of CG,
depression, hope, and PTG were completed by 85 youth (aged 7-18 years). Results
indicated a strong positive relationship between CG and depressive symptoms, an
inverse relationship between hope and depressive symptoms, and a moderate
positive relationship between hope and PTG. There was no significant association
between CG and hope or between CG and PTG. Higher levels of CG and lower levels
of hope independently predicted greater depressive symptoms, but PTG did not.
Results have implications for assessing positive outcomes in bereaved youth.
PMID- 28705040
TI - Minimal (Limited) Pseudohyperplastic Prostatic Adenocarcinoma in Needle Prostatic
Biopsy.
AB - BACKGROUND: Study of minimum adenocarcinoma has been done almost exclusively on
conventional acinar adenocarcinoma. Pseudohyperplastic adenocarcinoma can be
confused with benign lesions because of its well-differentiated appearance and
has not been studied when the biopsy shows few malignant glands (limited
carcinoma). METHODS: We reviewed 94 pseudohyperplastic adenocarcinomas diagnosed
in prostatic biopsies for a period of 12 years and selected those measuring less
than 1 mm or involving less than 5% of the biopsied tissue. We also reviewed 200
consecutive consultations. RESULTS: Four (4.2%) of the 94 cases were limited
pseudohyperplastic adenocarcinomas, and 3 were from consultations. Three of them
were mistaken for hyperplastic nodules, prostatic adenosis, or prostatic
intraepithelial neoplasm. The number of glands varied between 6 and 50 (average
23). Three nodular histological patterns were identified-nodular, adenosis-like,
and pseudohyperplastic carcinoma resembling prostatic intraepithelial neoplasia.
The diagnosis of adenocarcinoma was not related to the number of neoplastic
glands. Histological criteria that were useful included: crowded medium to large
glands, papillary infoldings, branching glands, straight luminal borders,
hyperchromatic nuclei, nucleomegaly, and apparent nucleoli. Areas of transition
to conventional acinar adenocarcinoma were useful in recognizing four of these
neoplasms, but were barely apparent in 2 of them. Hyperchromatic nuclei were
found in all cases, whereas apparent nucleoli and nucleomegaly were only present
in 4. CONCLUSIONS: The architectural and cytological criteria for limited acinar
adenocarcinoma are only partially useful in interpreting minimum
pseudohyperplastic adenocarcinomas. Knowledge of the criteria for malignancy in
both neoplasms is important in order to avoid underdiagnosis of malignancy.
PMID- 28705041
TI - Ionizing radiation induces EphA2 S897 phosphorylation in a MEK/ERK/RSK-dependent
manner.
AB - PURPOSE: The EphA2 tyrosine kinase is frequently overexpressed in human tumors
that are also treated with radiation. However, few studies have examined the
effect of radiation on the EphA2 receptor itself. The purpose of this project was
to investigate the impact of radiation on EphA2 to better understand mechanisms
of radioresistance. MATERIALS AND METHODS: Cell lines were exposed to X-rays and
assayed for changes in EphA2 protein levels and phosphorylation over time by
Western blotting. HEK293 cells stably expressing wild-type EphA2 or the S897A
mutant were analyzed for cell survival from X-rays. RESULTS: Treatment of
different cancer cell lines with 2 Gy of X-rays induced the phosphorylation of
EphA2 on S897 but no changes were found in EphA2 total levels or its tyrosine
phosphorylation. Radiation-induced S897 phosphorylation was unaffected by an AKT
inhibitor but blocked by a MEK or RSK inhibitor. HEK293 cells expressing the
EphA2 S897A mutant had a nearly 2-fold lower level of cell survival from X-rays
than cells expressing wild-type EphA2. CONCLUSIONS: These findings show that
radiation induces S897 EphA2 phosphorylation, an event associated with increased
cell survival. Therefore, targeting pathways that mediate EphA2 S897
phosphorylation may be a beneficial strategy to reduce radioresistance.
PMID- 28705042
TI - Musculoskeletal injuries in gastrointestinal endoscopists: a systematic review.
AB - INTRODUCTION: Gastrointestinal(GI) endoscopy forms a significant proportion of
clinicians' workloads. However, little attention is given to the ergonomic
aspects of endoscopy. This systematic review of musculoskeletal pain and/or
injuries in GI endoscopists aims to better understand the types of occupational
injuries resulting from endoscopic procedures and associated risk factors. Areas
covered: Systematic literature search conducted for articles evaluating
prevalence, risk factors and mechanism of musculoskeletal pain and/or injuries
related to GI endoscopy. In 13 included studies, 39-89% of surveyed endoscopists
reported pain and/or injuries related to endoscopy. Common areas of pain were the
back(15-57%), neck(9-46%), shoulders(9-19%), elbows(8-15%) and hands/fingers(14
82%). Risk factors included procedure volume, time spent doing endoscopy,
cumulative time in practice and endoscopist age. Experimental studies showed that
forces and loads placed on endoscopists' bodies during procedures place them at
risk of occupational injury. Areas of pain differed between novice and
experienced endoscopists implying separate mechanisms of injury. Expert
commentary: Comprehensive investigation into the prevalence, types,
pathophysiology and methods to minimise endoscopy-related musculoskeletal
injuries is vital to ensure the continued efficient provision of endoscopy
services in the face of rising demands worldwide. A paradigm shift is required in
endoscopic devices and techniques to improve safety and comfort.
PMID- 28705043
TI - Mannosylated liposomes improve therapeutic effects of paclitaxel in colon cancer
models.
AB - Mannose receptor (MR) is a highly effective endocytic receptor. It is closely
related to tumour immune escape and metastasis. We found that MR was highly
expressed in some colon cancer cell lines such as CT26 and HCT116 cells.
Therefore, MR might be a potential target in colon cancer therapy. In this study,
we aimed to develop mannosylated liposomes containing anticancer drug paclitaxel
and investigate the potential effects on targeted therapy for colon cancer.
Mannosylated liposomes were prepared by film dispersion method. Characterisation,
drug release behaviour, cytotoxicity, cellular uptake, anti-tumour efficacy and
safety profiles of liposomes were investigated. The results showed that
mannosylated liposomes had a higher CT26 cells uptake efficiency and tumour
inhibition rate, which might be due to the target effect to MR. And no notable
toxicity was observed. Taken together, these data demonstrated that mannosylated
liposomes could target colon cancer and improve the efficacy of chemotherapy.
PMID- 28705045
TI - Percutaneous coronary interventions of chronic total -occlusions; a review of
clinical indications, treatment strategy and current practice.
AB - Chronic total occlusions (CTOs) are commonly encountered in patients undergoing
coronary angiography, but percutaneous coronary intervention (PCI) for CTO is
currently infrequently performed owing to the perception of limited clinical
benefit, high complexity and cost of intervention, and perceived risk of
complications. Numerous observational studies have demonstrated that successful
CTO revascularization is associated with better cardiovascular outcomes and
enhanced quality of life (QOL). However, in the absence of randomized trials, its
prognostic benefit remains debated. Nevertheless, over the past decade the
interest in CTO-PCI has exponentially grown due to important developments in
dedicated equipment and techniques, resulting in high success and low
complication rates. A number of factors must be taken into consideration in
selecting patients for CTO-PCI, including presence of symptoms attributable to
the CTO, extent of ischaemia distal to the occlusion, and degree of myocardial
viability. In this review, we focus on the impact of CTO revascularization on
clinical outcomes and QOL and on appropriate patient selection. Data regarding
efficacy and safety of recent advances in PCI-CTO techniques will be discussed.
Steps involved in setting up a dedicated CTO program will be outlined and the
current CTO landscape in Belgium will be briefly highlighted. The overall aim of
this review is to promote a more balanced approach to management of patients with
a CTO.
PMID- 28705044
TI - The genetics of hair-cell function in zebrafish.
AB - Our ears are remarkable sensory organs, providing the important senses of balance
and hearing. The complex structure of the inner ear, or 'labyrinth', along with
the assorted neuroepithelia, have evolved to detect head movements and sounds
with impressive sensitivity. The rub is that the inner ear is highly vulnerable
to genetic lesions and environmental insults. According to National Institute of
Health estimates, hearing loss is one of the most commonly inherited or acquired
sensorineural diseases. To understand the causes of deafness and balance
disorders, it is imperative to understand the underlying biology of the inner
ear, especially the inner workings of the sensory receptors. These receptors,
which are termed hair cells, are particularly susceptible to genetic mutations -
more than two dozen genes are associated with defects in this cell type in
humans. Over the past decade, a substantial amount of progress has been made in
working out the molecular basis of hair-cell function using vertebrate animal
models. Given the transparency of the inner ear and the genetic tools that are
available, zebrafish have become an increasingly popular animal model for the
study of deafness and vestibular dysfunction. Mutagenesis screens for larval
defects in hearing and balance have been fruitful in finding key components, many
of which have been implicated in human deafness. This review will focus on the
genes that are required for hair-cell function in zebrafish, with a particular
emphasis on mechanotransduction. In addition, the generation of new tools
available for the characterization of zebrafish hair-cell mutants will be
discussed.
PMID- 28705046
TI - Pulmonary embolism with large oscillating thrombus: an alternative approach.
PMID- 28705047
TI - Galectin-3 correlates with arrhythmogenic right ventricular cardiomyopathy and
predicts the risk of ventricular -arrhythmias in patients with implantable
defibrillators.
AB - Background Arrhythmogenic right ventricular dysplasia (ARVD) is a heritable
disorder characterized by fibro-fatty replacement of right ventricular myocytes,
increased risk of ventricular arrhythmias, and sudden cardiac death. Galectin-3
(GAL3) is known to play an important role in a number of fibrotic conditions,
including cardiac fibrosis. Many studies have focused on the association between
GAL3 levels and cardiac fibrosis in heart failure. However, the role of GAL3 in
the pathogenesis of ARVD and ventricular arrhythmias has not yet been evaluated
thoroughly. The aim of this study was to explore GAL3 levels in patients with
ARVD and its association with ventricular arrhythmias. Methods Twenty-nine
patients with ARVD and 24 controls were included. All patients with ARVD had an
implantable cardiac defibrillator (ICD) for primary or secondary prevention.
Ventricular arrhythmia history was obtained from a chart review and ICD data
interrogation. Galectin-3 levels were measured using an enzyme-linked
immunosorbent assay. Results Patients with ARVD had higher plasma GAL3 levels
(16.9 +/- 2.6 ng/mL vs 11.3 +/- 1.8 ng/mL, P < 0.001) than the control group. Ten
patients had sustained or non-sustained ventricular arrhythmias during follow-up.
In the multivariable analysis, left ventricular disease involvement (HR: 1.05;
95% CI: [1.01-1.12]; P = 0.03); functional capacity >2 (HR: 1.21; 95% CI: [1.13
1.31]; P < 0.005); and GAL3 levels (HR: 1.05; 95% CI: [1.00-1.11]; P = 0.01)
independently predicted VT/VF. Conclusion We demonstrated that serum GAL3 was
significantly elevated in patients with ARVD. Also, serum GAL 3 levels could be
regarded as a candidate biomarker in the diagnosis of ARVD which needs to be
tested in larger prospective studies. In addition, GAL3 levels were higher in
patients with VT/VF as compared with those without VT/VF.
PMID- 28705048
TI - Calcified masses on the mitral valve in a patient on -haemodialysis.
PMID- 28705049
TI - Acquired Gerbode defect - a rare complication of myocardial infarction.
PMID- 28705050
TI - Association of Isotretinoin With Depression and Suicide: A Review of Current
Literature.
AB - Acne vulgaris, a condition that can affect people at any age, is the most common
cause of referral to a dermatologist. Isotretinoin (ITT) is the most effective
treatment available, but serious adverse effects, including a possible
association with depression and suicide, limit its use. We review the current
literature regarding the association of ITT with depression and suicide. Case
reports and database studies show a clear association, and this association is
biologically plausible. Although prospective studies have opposite results,
limitations make them unsuitable to identify a subgroup of patients who may be at
risk of developing depression or suicidal ideation with ITT. Overall, it seems
some people might be at risk, particularly those with a personal or family
history of mental disorder, but further studies are needed to identify those
patients who would benefit from an early referral to a mental health professional
when ITT is initiated. Currently, no conclusions can be drawn, and it seems
appropriate to regularly screen all patients on ITT for depressive symptoms and
suicidal ideation and promptly refer them to a mental health professional if any
are found.
PMID- 28705051
TI - Right-sided pulmonary venous return to the inferior vena cava: an exceptional
malformation.
PMID- 28705052
TI - Antioxidative mechanism in the course of varicose veins.
AB - Objective Our objective was to evaluate the state of oxidative stress in the
great saphenous varicose vein wall and blood of varicose vein patients taken from
the antecubital vein. Methods The superoxide dismutase, reduced glutathione (GSH)
and total antioxidant status were measured with commercially available
colorimetric kits in erythrocytes, plasma and varicose vein wall of 65 patients
(second degree of clinical state classification, etiology, anatomy and
pathophysiology) aged 22-70 (49 women, 16 men) in comparison to normal great
saphenous vein walls collected from 10 patients who underwent coronary artery
bypass graft and blood collected from 20 healthy individuals. Results A
statistically significant decrease (p < 0.001) in superoxide dismutase activity
in erythrocytes and the increase (p < 0.05) in superoxide dismutase activity in
varicose vein has been observed. There have been no significant changes in the
concentration of GSH in plasma and in varicose vein. The decreased concentration
of total antioxidant status in plasma (p < 0.001) and in varicose vein wall (p <
0.05) in comparison to the control has been noticed. Conclusion The varicose vein
patients are affected by oxidative stress. Our results indicate impaired
antioxidant defense mechanism in the blood of varicose vein patients. In contrast
to the blood, an increased process of antioxidant defense in the varicose vein
wall was noticed.
PMID- 28705053
TI - Cardiac amyloidosis: pathogenesis, clinical context, diagnosis and management
options.
AB - Amyloidosis covers a group of disorders that can manifest in virtually any organ
system in the body and is thought to be secondary to misfolding of extracellular
proteins with subsequent deposition in tissues. The precursor protein that is
produced in excess defines the specific amyloid type. This requires
histopathological confirmation using Congo-red dye with its characteristic
demonstration of green birefringence under cross-polarized light. There are three
main types of amyloidosis associated with cardiac involvement: light-chain (AL),
familial or senile (ATTR), and secondary (AA) amyloidosis. The frequency of
cardiac involvement and prognosis varies among each type. Amyloid cardiomyopathy
commonly manifests as heart failure and the presenting features are usually
dyspnoea, oedema, angina, pre-syncope and syncope. The diagnosis of cardiac
amyloidosis is very hard and can easily be misdiagnosed. Although the imaging
studies (such as echocardiography and cardiovascular magnetic resonance) may
guide the diagnosis, tissue biopsy is needed for confirmation. Management of
cardiac amyloidosis initially is to treat the underlying heart failure. Pacemaker
implantation is usually required in patients with any conduction abnormalities.
Transplantation is the next step with worsening heart failure. However, the aim
of any treatment in amyloidosis, irrespective of type, is to prevent further
deposition of amyloid while managing concurrent symptoms. In this manuscript, we
will discuss the pathogenesis of cardiac amyloidosis, diagnostic methods and
management options.
PMID- 28705054
TI - Radiofrequency perforation of the pulmonary valve: an efficient low cost
solution.
AB - Objective The aim of the study was to assess the feasibility of using commonly
available catheterization laboratory equipment for radiofrequency perforation of
the pulmonary valve in patients with pulmonary atresia and intact ventricular
septum. Methods The system (off-label use for all items) is made up of a co-axial
telescopic arrangement consisting of a 0.014" PT 2 TM coronary guidewire, for
insulation inside a 2.7-F microcatheter which has an inner lumen of 0.021". The
microcatheter was passed via a standard 4-F right coronary catheter to just below
the atretic pulmonary valve. Radiofrequency (RF) energy was delivered using a
standard electrosurgical system. In vitro testing had been performed and
indicated that 5-10 W for 2-5 s would be sufficient for valve perforation.
Results Radiofrequency perforation was successfully performed in all (n = 5,
100%) patients at a median age of 3 days (range: 1-36) and weight 2.7 kg (range
2.3-3.0). In one patient the pericardium was entered during the initial attempt;
the generator was put on coagulation mode during retrieval of the guidewire and
no haemopericardium occurred. The pulmonary valve was dilated in all; in three
patients (n = 3) the ductus arteriosus was stented during the same session.
Conclusion Results of the study show that it is feasible to perforate the
pulmonary valve safely using this system. Availability, simplicity and cost are
noteworthy benefits.
PMID- 28705055
TI - Ferrokinetics is associated with the left ventricular mass index in patients with
chronic kidney disease.
AB - Background Patients with chronic kidney disease (CKD) often have the complication
of anaemia. Usage of an erythropoietin-stimulating agent accelerates iron
deficiency because it promotes iron utilization. Recently, iron administration
was reported to be effective for patients with cardiac failure. We examined the
association between ferrokinetics and cardiac function in patients with CKD.
Methods In this cross-sectional study, we examined 558 patients (424 men and 134
women; mean age, 68.9 +/- 13.1 years) with CKD who were admitted to our hospital.
We assessed cardiac function by ultrasonography and ferrokinetics through
transferrin saturation (TSAT) and ferritin levels. Results The primary diseases
of CKD were nephrosclerosis (n = 247), diabetic nephropathy (n = 154), chronic
glomerulonephritis (n = 73), and others. The mean estimated glomerular filtration
rate was 16.9 +/- 9.3 mL/min/1.7 m2, and the haemoglobin (Hb) level was 11.0 +/-
1.7 g/dL. The median of TSAT was 28.05%, and patients were divided into two
groups: below (L-Ts) and above (H-Ts) the median. The median of ferritin was 122
ng/mL, and patients were divided into two groups: below (L-f) and above (H-f) the
median. We categorized four groups as H-Ts + H-F, H-Ts + L-F, L-Ts + H-F, and L
Ts + L-F. The Hb levels were 11.1 +/- 1.8, 11.3 +/- 1.4, 10.9 +/- 1.6, and 10.8
+/- 1.5 g/dL, respectively, and there was no difference between groups. However,
the left ventricular mass indices (LVMIs) were 122.6 +/- 46.6, 110.8 +/- 32.0,
118.3 +/- 36.0, 126.7 +/- 46.9, respectively (P = 0.0291). This tendency was
stronger in patients without cardiovascular events. Conclusion In patients with
CKD, there is an association between ferrokinetics and LVMI. We have to be
mindful not only of anaemia but also of ferrokinetics.
PMID- 28705056
TI - Combined use of nuclear phosphoprotein c-Myc and cellular phosphoprotein p53 for
hepatocellular carcinoma detection in high-risk chronic hepatitis C patients.
AB - BACKGROUND: Hepatocellular carcinoma (HCC) is a multistage process resulting from
various genetic changes. We aimed to determine nuclear phosphoprotein c-Myc and
cellular phosphoprotein p53 expression and to evaluate their importance in HCC
diagnosis. METHODS: One hundred and twenty chronic hepatitis C (CHC) patients (60
non-HCC CHC patients and 60 HCC patients who had a single small (<5 cm) tumour)
were recruited. The gene products of c-Myc and p53 were identified in liver
tissues and serum samples using immunostaining, western blot and ELISA. RESULTS:
Immunohistochemical detection of c-Myc and p53 with monospecific antibodies
revealed intense and diffuse cytoplasmic staining patterns. Accumulated mutant
proteins, released from tumour cells into the extracellular serum, were detected
at 62 KDa, for c-Myc, and 53 KDa, for p53, using western blotting. In contrast to
alpha feto-protein, there was a significant increase (p < 0.0001) in the
positivity rate of c-Myc (86.7% vs. 6.7%) and p53 (78.3% vs. 8.3%) in the
malignant vs. non-malignant patients. The parallel combination of c-Myc and p53
reach the absolute sensitivity (100%), for more accurate and reliable HCC
detection (specificity was 87%). CONCLUSION: c-Myc and p53 are potential HCC
diagnostic biomarkers, and convenient combinations of them could improve
diagnostic accuracy of HCC.
PMID- 28705057
TI - Applicability and procedural success rate of bioresorbable -vascular scaffolds
for percutaneous coronary intervention in an all-comer cohort of 383 consecutive
patients.
AB - Objectives The purpose of this study was to determine applicability and
procedural success of bioresorbable vascular scaffolds (BVS) for percutaneous
coronary intervention (PCI) in an all-comer cohort. Background BVS use in
bifurcations and severely calcified lesions is not recommended, and a relatively
large crossing profile may cause limitations. It is has never been studied how
widely BVS can be applied in all-comer cohorts. Methods In 383 consecutive
patients (acute coronary syndrome: 124, stable coronary disease 259), a BVS
(Absorb) was used as first-line device unless any of the following
contraindications were present: bifurcation with side branch >2.0 mm, reference
diameter <2.5 mm or >4.0 mm, required device length <12 mm, in-stent stenosis, or
contraindications to 6 months of DAPT. Patients and lesions were evaluated
regarding suitability for BVS treatment, procedural success (successful BVS
placement and residual stenosis <30%), and outcome. Results Of 588 lesions, 303
(52%) were unsuitable for BVS placement due to presence of a bifurcation (30% of
unsuitable lesions), reference -diameter >4.0 mm (13%) or <2.5 mm (12%),
contraindication to 6 months DAPT (13%), in-stent stenosis (14%), and desired
device length <12 mm (4%). If BVS use was attempted, procedural success with a
scaffold was 95% (271/285). Crossing failure occurred in 14 cases (5%), affected
lesions were significantly more calcified. After a mean follow-up period of 259
days, definite/probable scaffold thrombosis occurred in 1.1% of patients.
Conclusions Approximately one-half of lesions in an all-comer population can
successfully be treated with BVS. Crossing failure is rare.
PMID- 28705058
TI - Standardized Approach for ROI-Based Measurements of Proton Density Fat Fraction
and R2* in the Liver.
AB - OBJECTIVE: The purpose of this study was to evaluate the reproducibility
(interreviewer agreement) and repeatability (intrareviewer agreement) of ROI
sampling strategies to measure chemical shift-encoded (CSE) MRI-based liver
proton density fat fraction (PDFF) and R2* (1 / T2*). A secondary purpose was to
standardize ROI-based liver PDFF and R2* measurements by providing a compromise
between measurement reproducibility and repeatability and time burden for image
analysts. MATERIALS AND METHODS: CSE data from two cohorts were retrospectively
analyzed. Cohort A included 53 patients referred for abdominal MRI and healthy
subjects recruited for a comparison study of CT and MRI. Cohort B included 37
patients with suspected liver iron overload. Three reviewers measured liver PDFF
and R2* using previously reported ROI sampling strategies. Inter- and
intrareviewer agreement of liver PDFF and R2* were evaluated using Bland-Altman
analysis. RESULTS: Averaging largest-fit ROIs over the nine Couinaud segments
resulted in the narrowest limits of agreement (LOA) for liver PDFF and R2*
measurements in both cohorts. For PDFF, interreviewer agreement had mean LOA of
+/- 0.8% for cohort A and +/- 1.7% for cohort B. Intrareviewer agreement was +/-
0.5% for cohort A and +/- 0.9% for cohort B. For R2* interre-viewer agreement had
mean LOA of +/- 3.0 s-1 for cohort A and +/- 17.9 s-1 for cohort B. Intrare
viewer agreement was +/- 2.6 s-1 for cohort A and +/- 14.6 s-1 for cohort B. This
approach was the most time-burdensome, requiring a mean +/- SD of 149.7 +/- 8.6 s
per dataset. CONCLUSION: For improved reproducibility and repeatability of liver
PDFF and R2* measurements, clinicians and researchers should sample as much area
of the liver as possible using multiple large ROIs.
PMID- 28705060
TI - Usefulness of Multiparametric Ultrasound for Evaluating Structural Abnormality of
Transplanted Kidney: Can We Predict Histologic Abnormality on Renal Biopsy in
Advance?
AB - OBJECTIVE: The purpose of this study was to investigate the associations between
microscopic abnormalities of transplanted kidneys and sonography-based imaging
biomarkers, including elasticity, venous impedance index, arterial resistive
index, and size. MATERIALS AND METHODS: Between 2011 and 2015, 159 recipients
underwent sonography and biopsy of a transplanted kidney at our institution; 104
adult patients were included in this study. The maximal longitudinal length on
gray-scale images, arterial resistive index, and venous impedance index on
Doppler images and shear wave velocity on acoustic radiation force impulse
imaging or Young modulus on supersonic shear imaging were measured before biopsy.
The Banff criteria (2009 update), an international standardized classification
and scoring system for renal allograft pathology, were used to evaluate the
biopsy samples. Sonography parameters and clinical variables were analyzed with
individual and summed Banff scores. RESULTS: Spearman rank correlation
coefficients and ordinal logistic regression showed no association between
sonography parameters and summed Banff scores. Only the interval between
transplant and biopsy was significantly associated with summed Banff scores (p <
0.05). Univariate logistic regression analysis with individual Banff scores
showed associations of one Banff feature with arterial resistive index, three
with venous impedance index, and six with interval between transplant and biopsy
(p < 0.05). Sonoelastography parameters were not associated with any individual
Banff score. CONCLUSION: Neither sonoelastography parameter was associated with
any histopathologic change of renal allografts. Although arterial resistive index
and venous impedance index were related to a few individual Banff scores, length
of time between transplant and biopsy showed stronger correlation than any
imaging biomarkers with renal allograft deterioration.
PMID- 28705059
TI - Comparison of Triple-Drug Transcatheter Arterial Chemoembolization (TACE) With
Single-Drug TACE Using Doxorubicin-Eluting Beads: Long-Term Survival in 313
Patients.
AB - OBJECTIVE: We compared survival outcomes in 313 patients with unresectable
hepatocellular carcinoma (HCC) treated with two different transcatheter arterial
chemoembolization (TACE) regimens: triple-drug TACE or single-drug TACE using
drug-eluting beads. MATERIALS AND METHODS: In this retrospective study, patient
selection criteria were uniform. The triple-drug group (n = 166) underwent TACE
using ethiodized oil with doxorubicin, cisplatin, and mitomycin-C with a
microsphere embolic. The single-drug group (n = 147) underwent TACE using
doxorubicin-eluting beads. Group characteristics were classified and analyzed,
and survival was calculated using standard statistical methods. All patients were
followed until death. Those undergoing orthotopic liver transplant (OLT) were
also followed. RESULTS: There were no significant differences between the two
groups in terms of demographics, Child-Pugh class, or Okuda stage. With patients
undergoing OLT censored (n = 73), the mean (+/- standard error) survival in the
triple-drug group was 23.49 +/- 2.38 months, and the median survival was 16.00 +/
1.51 months. Mean survival in the single-drug bead group was 28.16 +/- 2.75
months, and the median survival was 15.00 +/- 1.50 months (p = 0.168). With
patients undergoing OLT censored, the mean and median survival for the total
cohort were 26.25 +/- 1.97 and 15.00 +/- 1.08 months, respectively. In the entire
cohort that did not undergo OLT, patients with Child-Pugh class A disease
survived significantly longer than did patients with Child-Pugh class B disease.
Elevated alpha-fetoprotein levels were associated with shorter survival, and
patients undergoing TACE with drug-eluting beads had shorter hospital stays.
Although a greater percentage annual survival was observed in patients undergoing
drug-eluting bead TACE who had Child-Pugh class A, Okuda stage I, and Barcelona
Clinic Liver Cancer classes A and B disease starting at 36 months, this suggested
survival advantage did not reach statistical significance. CONCLUSION: We found
no significant survival difference in patients with unresectable HCC treated with
triple-drug TACE compared with single-drug TACE using doxorubicin-eluting beads.
PMID- 28705061
TI - Communicating Uncertainty in the Radiology Report.
AB - OBJECTIVE: The purposes of this article are to explore the issue of diagnostic
uncertainty in radiology and how the radiology report has often fallen short in
this regard and to suggest approaches that can be helpful in addressing this
challenge. CONCLUSION: The practice of medicine involves a great deal of
uncertainty, which is an uncomfortable reality for most physicians. Radiologists
are more often than not faced with considerable diagnostic uncertainty and in
their written reports are challenged to effectively communicate that uncertainty
to referring physicians and others.
PMID- 28705062
TI - Ankle Traction During MRI of Talar Dome Osteochondral Lesions.
AB - OBJECTIVE: The objective of our study was to assess the impact of axial traction
during MRI of talar dome osteochondral lesions using a small-FOV coil. SUBJECTS
AND METHODS: A prospective study of 33 patients undergoing high-resolution MRI of
the ankle using a microscopy coil with and without axial traction was performed.
Two radiologists independently measured the tibiotalar joint space width and
semiquantitatively graded intraarticular joint fluid dispersion, cartilage
surface visibility of the osteochondral lesion, and cartilage surface visibility
elsewhere in the tibiotalar joint before and after traction. Patients were
instructed to report any discomfort during ankle traction. RESULTS: None of the
patients reported discomfort or other symptoms during ankle traction. The
tibiotalar joint space significantly increased (increase in cartilage-cartilage
distance, 0.5-0.7 mm; all, p < 0.05) after traction compared with before
traction. The degree of intraarticular joint fluid dispersion and the cartilage
surface visibility at the osteochondral lesion and elsewhere in the tibiotalar
joint improved after traction (all, p < 0.05). CONCLUSION: Traction MRI of the
ankle is safe and technically feasible. This study is the first to date to
investigate the effect of ankle traction on the MRI assessment of talar dome
osteochondral lesions. Traction improves cartilage surface visibility of talar
dome osteochondral lesions.
PMID- 28705063
TI - Postoperative CT of the Midfacial Skeleton After Trauma: Review of Normal
Appearances and Common Complications.
AB - OBJECTIVE: The objective of this article is to describe the CT appearance of the
midfacial skeleton after surgical repair of posttraumatic Le Fort,
nasoorbitoethmoidal (NOE), and frontal sinus fractures. Several of the more
commonly encountered complications will also be described. CONCLUSION: Surgery
after midfacial trauma is aimed at restoring both form and function. Knowledge of
the principal tenets of Le Fort, NOE, and frontal sinus fracture repair is vital
for radiologists to accurately assess the adequacy of treatment on postoperative
CT and provide meaningful reports for the surgeon.
PMID- 28705064
TI - Validation of Prostate Imaging Reporting and Data System Version 2 Using an MRI
Ultrasound Fusion Biopsy in Prostate Cancer Diagnosis.
AB - OBJECTIVE: The purpose of our study was to prospectively assess Prostate Imaging
Reporting and Data System (PI-RADS) version 2 using an MRI-ultrasound fusion
biopsy. SUBJECTS AND METHODS: This study included 295 consecutive patients with
478 lesions who underwent multiparametric MRI and subsequent MRI-ultrasound
fusion biopsy between December 2014 and September 2016. Lesions were assessed by
using an overall score of PI-RADS version 2. One radiologist assessed the
presence or absence of clinically significant prostate cancer in the whole gland
and in subgroups of the peripheral zone and transition zone by using cutoff
values of >= 4 and >= 3. Histologic examination of MRI-ultrasound fusion biopsy
specimens was used as the reference standard. Sensitivity, specificity, positive
predictive value (PPV), negative predictive value (NPV), and accuracy were
calculated to assess the utility of PI-RADS version 2 for the diagnosis of
clinically significant prostate cancer. RESULTS: The overall PI-RADS version 2
scores showed an accuracy of 82.2% (393/478) for the whole gland, with a cutoff
value of >= 4 granting sensitivity of 90.0% (90/100), specificity of 80.1%
(303/378), PPV of 83.3% (90/108), and NPV of 81.8% (303/370). The overall scores
showed accuracies of 84.7% (301/355) in the peripheral zone and 74.7% (92/123) in
the transition zone. When we applied an arbitrary overall score of >= 3, accuracy
was 68.6% (328/478), sensitivity was 94.6% (124/131), specificity was 58.7%
(204/347), PPV was 51.6% (124/240), and NPV was 85.7% (204/238). CONCLUSION: PI
RADS version 2 has an overall good performance for the diagnosis of clinically
significant prostate cancer.
PMID- 28705065
TI - Medicolegal-Malpractice and Ethical Issues in RadiologyYou're Sued for
Malpractice: Will Your Malpractice Insurance Company's Appointed Defense Attorney
Defend You or the Company?
PMID- 28705066
TI - Primary Cystic Lesions of the Retrorectal Space: MRI Evaluation and Clinical
Assessment.
AB - OBJECTIVE: The purpose of this study was to assess the a priori chance that
primary cystic lesions of the retrorectal space are malignant and to investigate
MRI characteristics that indicate malignancy. MATERIALS AND METHODS: Patients
referred to a center for colorectal surgery were recruited from 2000 to 2014.
Lesions were proven by clinical assessment and histopathology. MRI was performed
at 1.5 T with examinations evaluated by two radiologists. Interobserver agreement
was assessed (Cohen kappa) and differences between malignant and benign lesions
calculated (Fisher exact test). RESULTS: Twenty-eight patients (22 women, six
men; age range, 18-70 years) with 31 lesions were included. Lesions were
categorized as tailgut cysts (n = 16, 52%), teratomas (n = 9, 29%), lesions of
colorectal origin (n = 4, 13%), or neurogenic lesions (n = 2, 6%). Five patients
(18%) had malignant lesions. Colorectal lesions had the highest percentage of
malignancy (3/4, 75%). A solid tissue component was found in all five (100%)
malignant lesions and two (8%) of the benign lesions, which were both teratomas
(p < 0.05). Sensitivity and specificity for malignancy according to the presence
of a solid tissue component was 100% (5/5) and 92% (24/26). For unilocularity,
multilocularity, debris, septa, and wall thickening, differences were not
significant. Interobserver agreement was excellent (kappa = 1) for all
characteristics except debris (kappa = 0.795). CONCLUSION: The majority of
retrorectal cystic lesions are benign. The presence of a solid tissue component
should raise suspicion for malignancy.
PMID- 28705067
TI - Pancreatic Elastography From Acoustic Radiation Force Impulse Imaging for
Evaluation of Diabetic Microangiopathy.
AB - OBJECTIVE: The purposes of this study were to compare pancreatic shear-wave
velocity (SWV) in subjects with and those without diabetic microvascular
complications and to investigate the feasibility of pancreatic SWV in evaluating
diabetic microangiopathy. SUBJECTS AND METHODS: SWV measurements were
prospectively performed in 115 patients with diabetes mellitus and 115 healthy
persons by use of acoustic radiation force impulse imaging. Patients with
diabetes were divided into subgroups with and without microangiopathy. Pancreatic
SWV was compared in three groups. Factors associated with increased SWV were
studied. RESULTS: Pancreatic SWV increased significantly in the subgroups with
diabetes mellitus compared with the control group (p < 0.01). Especially, the SWV
in the pancreatic body was significantly higher when microangiopathy was present
(p < 0.01). In patients with diabetes, microangiopathy (standardized beta =
0.208, p = 0.022), age (standardized beta = 0.265, p = 0.004), and total
cholesterol level (standardized beta = 0.223, p = 0.011) were positively and
markedly correlated with high SWV in the pancreatic body. CONCLUSION: The
increased SWV in the pancreatic body was significantly related to the presence of
microangiopathy. It is feasible to use SWV in the pancreatic body to evaluate
diabetic microangiopathy.
PMID- 28705068
TI - Quantifying the Susceptibility Variation of Normal-Appearing White Matter in
Multiple Sclerosis by Quantitative Susceptibility Mapping.
AB - OBJECTIVE: The purpose of this study is to evaluate the magnetic susceptibility
of normal-appearing white matter (NAWM) in patients with multiple sclerosis (MS)
using quantitative susceptibility mapping. MATERIALS AND METHODS: Ninety-four
patients with relapse-remitting MS (RRMS) (37 with gadolinium-enhancing lesions
and 57 with only gadolinium-nonenhancing lesions) and 55 healthy control subjects
were included in this retrospective study. The susceptibility values of NAWM
relative to CSF in patients with MS were compared with those of white matter (WM)
in healthy control subjects and were correlated with the patient status of
gadolinium-enhancing lesions, disease duration, and expanded disability status
scale scores. RESULTS: All 37 patients with RRMS and gadolinium-enhancing lesions
also had gadolinium-nonenhancing lesions. Susceptibility values of NAWM in
patients with MS and only gadolinium-nonenhancing lesions (-18.29 +/- 8.03 parts
per billion [ppb]) were higher than those for WM in healthy control subjects (
25.81 +/- 6.02 ppb; p < 0.001) and NAWM in patients with gadolinium-enhancing
lesions (-25.64 +/- 6.55 ppb; p < 0.001). Susceptibility values of NAWM in
patients with MS with gadolinium-enhancing lesions were similar to those for WM
in healthy control subjects (p = 0.91). This trend was dependent on neither NAWM
region nor disease duration when the data were controlled for age. NAWM
susceptibility was not correlated with either disease duration or expanded
disability status scale (p > 0.05). CONCLUSION: In patients with RRMS and
gadolinium-nonenhancing lesions, the susceptibility values of NAWM decrease when
gadolinium-enhancing lesions appear, approaching values similar to those of WM in
healthy control subjects, suggesting that NAWM may contribute to the iron
accumulation observed in early active MS lesions.
PMID- 28705069
TI - Characterization of Incidental Renal Mass With Dual-Energy CT: Diagnostic
Accuracy of Effective Atomic Number Maps for Discriminating Nonenhancing Cysts
From Enhancing Masses.
AB - OBJECTIVE: The purpose of this study was to assess the diagnostic accuracy of
effective atomic number maps reconstructed from dual-energy contrast-enhanced
data for discriminating between nonenhancing renal cysts and enhancing masses.
MATERIALS AND METHODS: Two hundred six patients (128 men, 78 women; mean age, 64
years) underwent a CT renal mass protocol (single-energy unenhanced and dual
energy contrast-enhanced nephrographic imaging) at two different hospitals. For
each set of patients, two blinded, independent observers performed measurements
on effective atomic number maps from contrast-enhanced dual-energy data. Renal
mass assessment on unenhanced and nephrographic images, corroborated by imaging
and medical records, was the reference standard. The diagnostic accuracy of
effective atomic number maps was assessed with ROC analysis. RESULTS: Significant
differences in mean effective atomic numbers (Zeff) were observed between
nonenhancing and enhancing masses (set A, 8.19 vs 9.59 Zeff; set B, 8.05 vs 9.19
Zeff; sets combined, 8.13 vs 9.37 Zeff) (p < 0.0001). An effective atomic number
value of 8.36 Zeff was the optimal threshold, rendering an AUC of 0.92 (95% CI,
0.89-0.94), sensitivity of 90.8% (158/174 [95% CI, 85.5-94.7%]), specificity of
85.2% (445/522 [95% CI, 81.9-88.2%]), and overall diagnostic accuracy of 86.6%
(603/696 [95% CI, 83.9-89.1%]). CONCLUSION: Nonenhancing renal cysts, including
hyperattenuating cysts, can be discriminated from enhancing masses on effective
atomic number maps generated from dual-energy contrast-enhanced CT data. This
technique may be of clinical usefulness when a CT protocol for comprehensive
assessment of renal masses is not available.
PMID- 28705070
TI - Comparison of two European models estimating risk of -sudden cardiac death in
hypertrophic cardiomyopathy.
AB - Objective Hypertrophic cardiomyopathy (HCM) is associated with a risk of sudden
cardiac death (SCD). Several models have been developed to estimate SCD risk and
guide preventive therapy. The comparison of the previous 2003 with novel 2014 SCD
risk models have never been studied. Methods Over a year we included 103
consecutive HCM patients without previous cardiac arrest and/or ICD implanted
(65% males; aged 53.3 +/- 13.9 years; mean EF 62.3 +/- 18%). The SCD risk was
calculated for each patient. Results Based on the 2003 model, patients had
following scores: 0 points -15 (15%) patients, 1-28 (27%), 2-34 (33%), 3-18
(17%), >= 4-8 (8%). According to the 2014 model 83 (80%) had low risk, 12 (12%)
intermediate risk, and only 8 (8%) high risk. Patients who had an intermediate or
high risk in the 2003 model but a low risk in 2014 model were the oldest,
experienced less frequently syncope and nsVT, but had more often abnormal blood
pressure response to exercise and an intermediate LVOT gradient in comparison to
the patients who had consistently low or high risk in both models. Conclusions
Calculation of SCD risk using two models provides completely different risk
estimates and consequently different guidance on SCD primary prevention.
According to the 2003 model up to 85% of patients have indications for ICD,
whereas based on the 2014 risk model only 20% of the patients had non-negligible
SCD risk and are candidates for ICD therapy. SCD risk markers, used in the 2003
and 2014 models, have various discriminating power.
PMID- 28705071
TI - The Challenges of Providing Postpartum Education in Dar es Salaam, Tanzania:
Narratives of Nurse-Midwives and Obstetricians.
AB - Postpartum education can save lives of mothers and babies in developing
countries, and the World Health Organization recommends all mothers receive three
postpartum consultations. More information is needed to better understand how
postpartum education is delivered and ultimately improves postpartum health
outcomes. The purpose of this qualitative study was to examine how postpartum
care was delivered in three postnatal hospital clinics in Dar es Salaam,
Tanzania. Semistructured interviews with 10 nurse-midwives and three
obstetricians were conducted. Feminist poststructuralism guided the research
process. Postpartum education was seen to be an urgent matter; there was a lack
of supportive resources and infrastructure in the hospital clinics, and nurse
midwives and obstetricians had to negotiate conflicting health and traditional
discourses using various strategies. Nurse-midwives and obstetricians are well
positioned to deliver life-saving postpartum education; however, improvements are
required including increased number of nurse-midwives and obstetricians.
PMID- 28705072
TI - Short and long-term results after endovascular management of vascular
complications during transfemoral aortic valve implantation.
AB - Background Vascular injury and access site complications in the contemporary
setting of transcatheter aortic valve implantation (TAVI) are known to be
associated with increased mortality and morbidity. The aim of our study was to
analyse the feasibility and safety of percutaneous treatment of such vascular
complications using a stent graft. Methods Between January 2010 and April 2013,
36 TAVI patients developed severe access site complications and underwent
subsequent interventional treatment with a covered stent. Acute treatment success
was confirmed by angiography immediately after the implantation of the stent
graft, with clinical long-term patency follow-up being assessed by duplex
ultrasound. Results Of the 36 patients evaluated, percutaneous treatment of the
acute access site bleeding was successful in 35 patients (97%), with one patient
requiring surgical intervention due to insufficient haemostasis after stent graft
implantation. A subset of 5 patients underwent successful ipsilateral stent graft
implantation, either because crossover sheath placement was not feasible (n = 1),
or intentionally with an even sheathless approach in an effort to reduce vessel
injury (n = 4). After a mean follow-up of 22 +/- 8 months, stent graft patency
was confirmed by duplex ultrasound in 13 patients with an additional 5 patients
reporting to be free from symptoms and claudication. Thirteen patients died
within the first 24 months after the procedure, however, none was due to access
vessel complications. Five patients were lost for follow-up. Conclusions Our data
confirm that endovascular treatment of access site complications related to TAVI
is feasible, safe and efficacious, resulting in long-term vascular patency.
PMID- 28705073
TI - Re-visioning evidence: Reflections on the recent controversy around gender
selective abortion in the UK.
AB - Reports in the British media over the last 4 years have highlighted the schisms
and contestations that have accompanied the reports of gender selective abortions
amongst British Asian families. The position that sex-selection may be within the
terms of the 1967 Abortion Act has particularly sparked controversy amongst
abortion campaigners and politicians but equally among medical practitioners and
the British Pregnancy Advisory Service who have hitherto tended to stay clear of
such debates. In what ways has the controversy around gender-based abortion led
to new framings of the entitlement to service provision and new ways of thinking
about evidence in the context of reproductive rights? We reflect on these issues
drawing on critiques of what constitutes best evidence, contested notions of
reproductive rights and reproductive governance, comparative work in India and
China as well as our involvement with different groups of campaigners including
British South Asian NGOs. The aim of the paper is to situate the medical and
legal provision of abortion services in Britain within current discursive
practices around gender equality, ethnicity, reproductive autonomy, probable and
plausible evidence, and policies of health reform.
PMID- 28705074
TI - Factors associated with severity of sleep apnoea syndrome in patients with
chronic kidney disease.
AB - Background In patients with chronic kidney disease (CKD), prevalence of sleep
apnoea syndrome (SAS) is reported to be markedly high. However, the factors
associated with severity of SAS in such patients rarely have been reported.
Methods This was a cross-sectional study of 100 stable non-dialysis patients with
CKD who attended a CKD educational programme from April 2014 to August 2015.
Diagnosis of SAS and its severity were assessed using a type-3 portable monitor.
Results Eighty-six men and 14 women with a mean age of 71.6 +/- 9.7 years were
included. Mean apnoea-hypopnoea index (AHI) was 26.0 +/- 13.8. Severe SAS was
seen in 39 patients. Significant differences in brain natriuretic peptide (BNP)
level (213.6 +/- 329.6 pg/mL vs 107.8 +/- 141.3 pg/mL, P < 0.05) and
cardiothoracic ratio (CTR, 52.4% +/- 6.3% vs 49.6% +/- 5.7%, P < 0.05) were seen
between patients with and without severe SAS. After adjusting for various
parameters, BNP level, CTR, and diameter of the inferior vena cava at the end of
inhalation were found to correlate with AHI. Conclusions In patients with CKD,
prevalence of severe SAS is extremely high. In these patients, fluid retention,
rather than systolic or diastolic function, correlates with severity of SAS.
PMID- 28705075
TI - Higher adherence to the Mediterranean diet is inversely associated with having
hypertension: is low salt intake a mediating factor?
AB - Blood pressure (BP) is a major risk factor for population health worldwide and a
preventable disease through lifestyle modification. The aim of this study was to
assess the association between adherence to the Mediterranean diet (MD) and
occurrence of hypertension in a Mediterranean cohort. Demographic and dietary
data of 1937 adults were collected in 2014-2015 from the general population of
Catania, Sicily (Italy). Food frequency questionnaires and a MD adherence score
were used to assess exposure variables. Higher adherence to the MD was inversely
associated with hypertension. However, this association was no more significant
after adjustment for sodium and potassium intake. These results suggest that salt
may exert a mediating effect of high adherence to the MD towards hypertension.
PMID- 28705076
TI - Elucidation of stable intermediates in urea-induced unfolding pathway of human
carbonic anhydrase IX.
AB - Human carbonic anhydrase IX (CAIX) has evolved as a promising biomarker for
cancer prognosis, due to its overexpression in various cancers and restricted
expression in normal tissue. However, limited information is available on its
biophysical behavior. The unfolding of CAIX in aqueous urea solution was studied
using all-atom molecular dynamics simulation approach. The results of this study
revealed a stable intermediate state along the unfolding pathway of CAIX. At
intermediate concentrations of urea (2.0-4.0 M), the protein displays a native
like structure with a large population of its secondary structure and hydrophobic
contacts remaining intact in addition to small confined overall motions. Beyond
4.0 M urea, the unfolding is more gradual and at 8.0 M urea the structure is
largely collapsed due to the solvent effect. The hydrophobic contact analysis
suggests that the contact in terminal alpha-helices is separated initially which
propagates in the loss of contacts from centrally located beta-sheets. The
reduction of 60-65% tertiary contacts in 7.0-8.0 M urea suggested the presence of
residual structure in unfolded state and is confirmed with structural snap shot.
Free energy landscape analysis suggested that unfolding of CAIX exists through
the different intermediate states.
PMID- 28705077
TI - Fifty years of hemodialysis access literature: The fifty most cited publications
in the medical literature.
AB - Objectives The modern era of hemodialysis access surgery began with the
publication in 1966 by Brescia et al. describing the use of a surgically created
arteriovenous fistula. Since then, the number of patients on chronic hemodialysis
and the number of publications dealing with hemodialysis access have steadily
increased. We have chronicled the increase in publications in the medical
literature dealing with hemodialysis access by evaluating the characteristics of
the 50 most cited articles. Methods We queried the Science Citation Index from
the years 1960-2014. Articles were selected based on a subject search and were
ranked according to the number of times they were cited in the medical
literature. Results The 50 most frequently cited articles were selected for
further analysis and the number of annual publications was tracked. The landmark
publication by Dr Brescia et al. was unequivocally the most cited article dealing
with hemodialysis access (1109 citations). The subject matter of the papers
included AV fistula and graft (9), hemodialysis catheter (9), complications and
outcomes (24), and other topics (8). Most articles were published in nephrology
journals (33), with fewer in surgery (7), medicine (7), and radiology (3)
journals. Of the 17 journals represented, Kidney International was the clear
leader, publishing 18 articles. There has been an exponential rise in the
frequency of publications regarding dialysis access with 42 of 50 analyzed papers
being authored after 1990. Conclusion As the number of patients on hemodialysis
has increased dramatically over the past five decades, there has been a
commensurate increase in the overall number of publications related to
hemodialysis access.
PMID- 28705078
TI - Sensitivity, specificity, and allowing the data to speak.
PMID- 28705079
TI - How to define the hemodynamic significance of an equivocal iliofemoral artery
stenosis: Review of literature and outcomes of an international questionnaire.
AB - Purpose The goal of the study was to review current literature regarding the
diagnosis of equivocal (50-70%) iliofemoral artery stenosis and compare these
findings with the daily practice of an international panel of endovascular
experts. Methods The Medline Database was searched for relevant publications, and
an electronic survey was sent to experts in the field covering the following
topics: definition of an equivocal iliofemoral artery stenosis, angiographic
visualization and investigation protocols of an equivocal stenosis, intra
arterial pressure measurements, and definition of hemodynamic significance of an
equivocal iliofemoral artery stenosis using a physiologic measure. Results Of the
37 invited endovascular experts, 21 (53.8%) agreed to participate in the survey.
Analysis of existing literature shows that the level of evidence for diagnosing
equivocal iliofemoral artery stenosis is mediocre and is not being implemented by
experts in the field. Conclusion Studies have shown that a stenosis of between
50% and 70% iliofemoral lumen diameter reduction shows a wide range of trans
stenotic pressure gradients. Equivocal iliofemoral artery stenosis can best be
identified using three-dimensional quantitative vascular analysis software.
Although evidence for a clear hemodynamic cutoff point is weak, performing trans
lesion intra-arterial pressure measurements at rest and during maximal hyperemia
is preferred. Diagnosing iliofemoral artery stenosis solely on lumen diameter
reduction is inadequate.
PMID- 28705080
TI - The Prevalence of Zinc Deficiency and its Correlation with Iron Status and
Economical Living Area in 9 - 12-Year-Old Children.
AB - OBJECTIVE: This study aimed firstly to assess zinc and iron status of 9-12-year
old children of Tehran and secondly to determine a cut-off for circulating
biomarkers of iron status to identify children at increased risk of zinc
deficiency. RESEARCH METHODS & PROCEDURES: In a cross-sectional study,
demographic and anthropometric data from 505 boys and 467 girls aged 9-12 years
from Tehran primary schools were obtained and their zinc and iron status was
assessed. RESULTS: The prevalence of zinc deficiency, anemia, and iron depletion
was 12.4, 14.6, and 9.5%, respectively. Serum zinc con-centration was
significantly lower in children with anemia than in their non-anemic peers (p <
0.05). There was no significant association between zinc and iron status and
serum high sensitivity C-reactive protein. Zinc-deficient children, compared to
those with normal serum zinc, had significantly shorter stature (139.7 (+/-6.9)
vs 141.3 (+/-7.1) cm, CI: -2.97 - -0.2, p = 0.029). Serum zinc concentration was
the predictor of height in the children (p = 0.004, CI: 0.01 - 0.054). A logistic
regression model showed an increased risk of low serum zinc and ferritin in
children who resided in economically poor regions (OR = 1.65, p = 0.043; OR =
1.92, p = 0.016, respectively). Using ROC curve and Youden index, the optimal cut
off value for serum ferritin to indicate zinc deficiency was 14.9 ug/L
(sensitivity = 90%, specificity = 61%). CONCLUSIONS: Lowered zinc and iron status
among the children in deprived regions is likely to be due to poor quality of
diet. Moreover, children with serum ferritin lower than 14.9 ug/L must be
carefully assessed for concomitant zinc deficiency.
PMID- 28705081
TI - An evaluation and comparison of myeloperoxidase enzymatic activity during initial
orthodontic alignment: an in vivo study.
AB - INTRODUCTION: Tooth movement during orthodontic treatment is possible because of
mechanical force-induced inflammation and remodelling in the periodontal
ligament. Variation in the inflammatory response might be anticipated with
initial aligning archwires of different composition. Myloperoxidase (MPO) is an
enzyme found in neutrophil granules that represents an important marker of
inflammation. The aim of this study was to measure MPO enzyme activity during
initial alignment with orthodontic arch wires of different alloy types. MATERIALS
AND METHODS: MPO activity was determined in gingival crevicular fluid (GCF) from
a sample of 60 patients divided into three groups during initial orthodontic
alignment with three types of arch wire (0.016-inch superelastic (SE) NiTi; 0.016
inch heat-activated (HANT) NiTi and 0.00175-inch multistranded stainless steel).
MPO activity was measured at baseline, 2 hours, 7 and 14 days after appliance
activation. RESULTS: MPO activity was significantly increased in GCF at 2 hours
(P < 0.01), 7 and 14 days in all groups compared to baseline. Enzymatic activity
was highest in the SE NiTi group followed by HANT and multistranded stainless
steel groups but with no significant difference between SE NiTi and HANT groups.
CONCLUSION: SE and HANT NiTi arch wires produce an increased inflammatory
response based upon MPO activity during initial levelling and alignment compared
to multistranded stainless steel.
PMID- 28705082
TI - Projected Improvements in Accelerated Partial Breast Irradiation Using a Novel
Breast Stereotactic Radiotherapy Device: A Dosimetric Analysis.
AB - Accelerated partial breast irradiation has caused higher than expected rates of
poor cosmesis. At our institution, a novel breast stereotactic radiotherapy
device has demonstrated dosimetric distributions similar to those in
brachytherapy. This study analyzed comparative dose distributions achieved with
the device and intensity-modulated radiation therapy accelerated partial breast
irradiation. Nine patients underwent computed tomography simulation in the prone
position using device-specific immobilization on an institutional review board
approved protocol. Accelerated partial breast irradiation target volumes
(planning target volume_10mm) were created per the National Surgical Adjuvant
Breast and Bowel Project B-39 protocol. Additional breast stereotactic
radiotherapy volumes using smaller margins (planning target volume_3mm) were
created based on improved immobilization. Intensity-modulated radiation therapy
and breast stereotactic radiotherapy accelerated partial breast irradiation plans
were separately generated for appropriate volumes. Plans were evaluated based on
established dosimetric surrogates of poor cosmetic outcomes. Wilcoxon rank sum
tests were utilized to contrast volumes of critical structures receiving a
percentage of total dose ( Vx). The breast stereotactic radiotherapy device
consistently reduced dose to all normal structures with equivalent target
coverage. The ipsilateral breast V20-100 was significantly reduced ( P < .05)
using planning target volume_10mm, with substantial further reductions when
targeting planning target volume_3mm. Doses to the chest wall, ipsilateral lung,
and breast skin were also significantly lessened. The breast stereotactic
radiotherapy device's uniform dosimetric improvements over intensity-modulated
accelerated partial breast irradiation in this series indicate a potential to
improve outcomes. Clinical trials investigating this benefit have begun accrual.
PMID- 28705083
TI - Pyrrolo[2,3-d]pyrimidines active as Btk inhibitors.
AB - INTRODUCTION: Btk is a tyrosine kinase dysregulated in several B-cell
malignancies and autoimmune diseases, and this has given rise to a search for Btk
inhibitors. Nevertheless, only one Btk inhibitor, ibrutinib, has been approved to
date, although other compounds are currently being evaluated in clinical trials
or in preclinal stages. Area covered: This review, after a brief introduction on
Btk and its inhibitors already in clinical trials, focusses on pyrrolo[2,3
d]pyrimidine derivatives patented in the last five years as Btk inhibitors.
Indeed, the pyrrolo[2,3-d]pyrimidine scaffold, being a deaza-isostere of adenine,
the nitrogenous base of ATP, is an actively pursued target for Btk inhibitors.
The patent literature since 2012 have been extensively investigated, pointing out
the general features of the patented compounds and, when it is possible, their
mechanism of action. Expert opinion: The recently patented pyrrolo[2,3
d]pyrimidines, acting as reversible or irreversible inhibitors, showed a very
interesting in vitro activity. For this reason, the development of compounds
endowed with this scaffold could afford a significant impact in the search for
drug candidates for the treatment of immune diseases or B-cell malignancies.
PMID- 28705084
TI - The large adult abdominoscrotal hydrocoele: does it require of posterior inguinal
canal wall reinforcement?
PMID- 28705085
TI - International Survey of ALS Experts about Critical Questions for Assessing
Patients with ALS.
AB - OBJECTIVE: To define an applicable dataset for ALS patient registries we weighted
specific clinical items as scored by worldwide ALS experts. METHODS: Sixty
participants were invited based on relevant clinical work, publications and
personal acquaintance. They rated 160 clinical items consensually agreed by the
members of our project, incorporating specialists from five European Centres.
Scoring scheme was defined as: 1 - essential; 2 - important; 3 - not very
important. A mixed effect model was applied to rank items and to find possible
correlations with geographical region (Europe vs. outside Europe). RESULTS: We
received 40 responses, 20 from Europe and 20 from outside; 42/160 data were
scored as essential by >50% of the respondents, including: date of birth, gender,
date of disease onset, date of diagnosis, ethnicity, region of onset, predominant
upper neuron (UMN) or lower motor neuron (LMN) impairment, proximal versus distal
weakness, respiratory symptoms, dysarthria, weight loss, signs of LMN/UMN
involvement, emotional incontinence, cognitive changes, respiratory signs, neck
weakness, body mass index, ALSFRS-R at entry, ALSFRS-R subscores at entry, timing
and pattern of spreading and staging, electromyography, spirometry, MRI, CK
level, riluzole intake, genetic background, history of physical exercise and
previous and current main occupation. Four components were scored as non
relevant, including place of birth, blood pressure and pain at onset. There was
no significant difference between regions (European vs. non-European countries).
CONCLUSIONS: Our study identified a consensual set of clinical data with 42
specific items that can be used as a minimal data set for patient registers and
for clinical trials.
PMID- 28705086
TI - Longitudinal Relations Between Childhood Maltreatment, Maltreatment-Specific
Shame, and Postpartum Psychopathology.
AB - The persistence of shame-based reactions to child maltreatment (CM) has been
associated with poor posttraumatic adjustment. Despite evidence that the
postpartum period is a vulnerable time for women with CM histories, little is
known about the consequences of maltreatment-specific (MS) shame for postpartum
functioning. The current study examined individual differences in MS shame among
a sample of women during the postpartum period ( n = 100) as well as prospective
relations from MS shame to postpartum psychopathology at 6-, 12-, 15-, and 18
month postpartum. Linear growth curve (LGC) analyses showed that MS shame
predicted higher levels of depression symptoms but not post-traumatic stress
disorder (PTSD) symptoms at all time points whereas path analyses showed that
shame mediated the relations from multi-maltreatment to both depression and PTSD
symptoms at all time points. Results point to the long-term consequences of MS
shame during postpartum and the importance of attending to shame in clinical care
of maltreatment survivors who present with postpartum psychopathology.
PMID- 28705087
TI - Moving backwards, moving forward: the experiences of older Filipino migrants
adjusting to life in New Zealand.
AB - PURPOSE: To explore the experiences of older Filipino migrants adjusting to
living permanently in New Zealand. METHOD: The qualitative descriptive approach
taken in this study involved 17 individual face-to-face interviews of older
Filipino migrants in New Zealand. RESULTS: Three main themes emerged from the
data. The first theme was "moving backwards and moving forward", which described
how these older Filipino migrants adjusted to challenges they experienced with
migration. The second theme was "engaging with health services" and presented
challenges relating to the New Zealand healthcare system, including a lack of
knowledge of the nature of health services, language barriers, and differences in
cultural views. The third theme, "new-found home", highlighted establishing a
Filipino identity in New Zealand and adjusting to the challenges of relocation.
CONCLUSION: Adjustment to life in New Zealand for these older Filipino migrants
meant starting over again by building new values through learning the basics and
then moving forward from there.
PMID- 28705088
TI - A study of comparative modelling, simulation and molecular dynamics of CXCR3
receptor with lipid bilayer.
AB - The G-coupled receptors seen on the cell surface are composites with a lipid
bilayer. The chemokines are kind of G-coupled receptor which majorly involved in
the activation and downstream signalling of the cell. In general, many G-coupled
receptors lack their 3D structures which become a hurdle in the drug designing
process. In this study, comparative modelling of the CXCR3 receptor was carried
out, structure evaluation was done using various tools and softwares.
Additionally, molecular dynamics and docking were performed to prove the
structural quality and architecture. Interestingly, the studies like toggle
switch mechanism, lipid dynamics, virtual screening were carried out to find the
potent antagonist for the CXCR3 receptor. During virtual screening 14,303 similar
molecules were retrieved among them only four compounds have an ability to
interact with a crucial amino acid residue of an antagonist. Hence, these
screened compounds can serve as a drug candidate for a CXCR3 receptor, but
further in vitro and in vivo studies are ought to do to prove its same efficacy.
PMID- 28705089
TI - Electrochemical degradation of psychoactive drug caffeine in aqueous solution
using graphite electrode.
AB - In this study, the electrochemical degradation of caffeine (1,3,7
trimethylxanthine) in aqueous solution by a graphite electrode was investigated.
Electrochemical degradation was tested by the cyclic voltametry technique
performed in the potential range of -1.0 to +1.0 V versus Ag/AgCl, which
confirmed the electro-activity of the selected caffeine. The effects of the
treatment process variables, such as initial pH, current density, electrolyte
concentration and electrolysis time on the degradation of caffeine, were
explored. During the various stages of electrolysis, parameters such as chemical
oxygen demand (COD), total organic carbon (TOC) were analysed. The maximum COD
and TOC removal efficiencies of 85% and 77% were achieved at neutral pH 7,
operated at a current density of 5.1 mA/cm2, electrolyte (Na2SO4) concentration
of 0.1 M and at 240 min electrolysis time. From this study, it can be concluded
that the electrochemical treatment process could effectively reduce the COD and
TOC from the caffeine in aqueous medium. The degradation of the caffeine was
confirmed by UV spectra, IR spectra and HPLC analysis.
PMID- 28705090
TI - The safety of available treatments options for neuroendocrine tumors.
AB - INTRODUCTION: Neuroendocrine neoplasms (NEN) represent a heterogeneous group of
malignancies generally characterized by low proliferation and indolent course.
However, about half of the newly diagnosed cases are metastatic and require long
term systemic therapies. Areas covered: This review revises the literature to
summarize the current knowledge upon safety of all systemic treatment options
available. Thirty three different clinical studies have been considered,
including 4 on somatostatin analogues (SSA), 5 on targeted therapies, 10 on
peptide receptor radionuclide therapy (PRRT), and 14 on chemotherapy. Expert
opinion: SSA are safe and well tolerated without any relevant severe adverse
event and very low treatment discontinuation rate. Targeted therapies show a
satisfying safety profile. Most adverse events are grade 1-2 and easy manageable
with dose reduction or temporary interruption. PRRT is manageable and safe with a
low rate of grade 3-4 adverse events. However, severe renal and hematologic
toxicity may occur. Chemotherapy is usually considered after previous therapeutic
lines. Therefore, these subjects are more susceptible to experience adverse
events due to cumulative toxicities or poor performance status. The available
systemic treatment options are generally well tolerated and suitable for long
term administration. Cumulative toxicity should be taken in account for the
definition of therapeutic sequence.
PMID- 28705091
TI - Molecular approaches to potentiate cisplatin responsiveness in carcinoma
therapeutics.
AB - INTRODUCTION: Cisplatin has been considered as the crucial regimen of widely
prescribed chemotherapy treatment for cancer. The advancing treatment of cancers
has reached the border line, where tumors show resistance to cisplatin and may
thwart its use. Other than issues of drug resistance, cisplatin has been reported
to evince side effects such as nephrotoxicity and ototoxicity. Therefore, there
is a compelling need to untangle the problems associated with cisplatin treatment
in carcinoma. Areas covered: In this review, we summarize the current status of
combinatorial options to bring about better pre-clinical and clinical cisplatin
drug responses in carcinoma. We begin with problems associated with cisplatin
drugs and current avenues such as depicting molecular modulation of enhanced
influx and reduced efflux. We also discuss the scope of the DNA damage response
landscape and contribution of regulatory small RNAs towards potentiation of
cisplatin responses. Expert commentary: The extensive use of cisplatin and
incessant high drug dose have prompted the scientific community to limit the
burden of cisplatin without compromising therapeutic success. Currently, there
are reports on the potential use of other non-toxic small molecule inhibitors,
interference RNAs and peptide mimetics to get rid of cellular adversities
responsible for cisplatin resistance and high dose effects.
PMID- 28705092
TI - Serum allantoin and aminothiols as biomarkers of chronic heart failure.
AB - Background Oxidative stress (OS) represents the primary mediator of chronic heart
failure (CHF) development and progression. It is well established that
homocysteine is able to generate reactive oxygen species. Small amounts of
allantoin in human serum result from free radical action on urate and may provide
a stable marker for in vivo free radical activity. To investigate whether some
easily measurable indexes such as antioxidants (uric acid, glutathione) and
related molecules (allantoin, homocysteine and cysteine) can serve as OS
biomarkers. Methods We investigated 75 stable CHF patients. Aminothiols and
purine compound levels were determined by capillary electrophoresis. Results The
homocysteine level was markedly elevated in CHF patients, whatever the aetiology.
Parameters of the transsulfuration pathway and the investigated purine compounds
were significantly increased. Conversely, total glutathione was decreased. The
allantoin/uric acid ratio was significantly higher in CHF patients with an
hyperhomocysteinaemia >17 MUmol/L. All parameters of the transsulfuration and
purine degadation pathways were significantly correlated, suggesting an OS in CHF
patients. Conclusion Our data show an imbalance of serum aminothiols and purine
compounds in these CHF patients on adapted therapy. We suggest that the
evaluation and control of these new markers may help improve the OS that
participates in the progression of the disease.
PMID- 28705093
TI - Incentive Use for Improving Maternal Health: Perspective From Behavioral Science.
AB - Incentive use to improve maternal health behavior has been controversial, and
guidelines to effectively design and implement such an intervention have been
published. This commentary briefly describes a perspective from behavioral
science for the existing guideline on the development of an incentive-based
intervention to change maternal health behaviors. It is recommended to emphasize
the saliency of incentives as an important variable to maintain the intervention
effect while addressing barriers to feasibility and sustainability.
PMID- 28705094
TI - Auditing the use and assessing the clinical utility of microscopy as a point-of
care test for Neisseria gonorrhoeae in a Sexual Health clinic.
AB - We assessed whether urethral microscopy was performed as per clinic protocol for
male clinic attendees reporting contact with Neisseria gonorrhoeae (GC), urethral
symptoms or given a diagnosis of epididymo-orchitis (EO) over a 12-month period
(9732 patients). Prevalence of gonorrhoea in the contacts, urethral symptoms and
EO groups was 50, 12.7 and 1.6%, respectively. Microscopy was performed reliably
for contacts (96%), those with discharge/dysuria with evidence of urethritis on
examination (98%), but not those with EO (43%). We explored the clinical utility
of microscopy as a point-of-care test for identifying urethral GC in each
subgroup, using the APTIMA Combo 2 CT/GC nucleic acid amplification test as the
comparator (1710 patients). Sensitivity of microscopy for each subgroup was good;
there was no statistical difference between subgroup sensitivity using Fisher's
exact test. Microscopy is valuable to ensure prompt diagnosis and contact
tracing. All GC contacts were treated 'epidemiologically'; however, half of GC
contacts did not have GC. Microscopy identified the majority of GC cases,
including amongst contacts (71% of heterosexual contacts, 66% of contacts
reporting sex with men). We propose that epidemiological treatment for GC
contacts should be reconsidered on the grounds of antibiotic stewardship,
favouring use of microscopy to guide treatment decisions.
PMID- 28705095
TI - Meta-synthesis of fathers' experiences raising children on the autism spectrum.
AB - Parents raising children with autism have distinct experiences that influence
their well-being, relationships, engagement with the public, and interaction with
education and healthcare systems. However, experiences of fathers of children
with autism have been largely overlooked by researchers. This meta-synthesis is
our synthesis of qualitative accounts of fathers' experiences and we included
peer reviewed and gray literature articles that: (1) reported primary qualitative
research, (2) included fathers of children with autism as participants, and (3)
reported qualitative findings on the first-hand experiences of fathers of
children with autism. Studies were appraised for quality and many theoretical and
methodological deficiencies identified. Six studies met quality appraisal
criteria and three main themes of findings from these studies were generated: (1)
adaptation and concern with the future, (2) the importance of cultural context,
and (3) reverence for one's child and new opportunities. Fathers' experiences
illuminate a need for father-oriented resources that recognize fathers' value in
children's lives.
PMID- 28705096
TI - Autism spectrum disorders in adult outpatients with obsessive compulsive disorder
in the UK.
AB - OBJECTIVES: Patients with obsessive compulsive disorder (OCD) frequently show
traits of autism spectrum disorders (ASD). This is one of the first studies to
explore the clinical impact of the overlap between OCD and ASD as a categorical
diagnosis. METHODS: A cross-sectional survey in 73 adult outpatients with DSM-IV
OCD. Autistic traits were measured using the Autism-Spectrum Quotient (AQ). A
clinical estimate ASD diagnosis was made by interview using DSM-IV-TR criteria.
OCD patients with and without autistic traits or ASD were compared on demographic
and clinical parameters and level of OCD treatment-resistance based on treatment
history. RESULTS: Thirty-four (47%) patients scored above the clinical threshold
on the AQ (>=26) and 21 (27.8%) met diagnostic criteria for ASD. These diagnoses
had not been made before. Patients with autistic traits showed a borderline
significant increase in OCD symptom-severity (Yale-Brown Obsessive Compulsive
Scale (Y-BOCS); p = .054) and significantly increased impairment of insight
(Brown Assessment of Beliefs Scale; p = .01). There was a positive correlation
between AQ and Y-BOCS scores (p = .04), but not with OCD treatment resistance.
CONCLUSION: There is a high prevalence of previously undiagnosed ASD in patients
with OCD. ASD traits are associated with greater OCD symptom-severity and poor
insight.
PMID- 28705097
TI - Transfusion Refusal and the Shifting Limits of Multicultural Accommodation.
AB - The refusal of blood products by Jehovah's Witness patients has provoked court
proceedings, social science research, and contemporary fiction, all of which
emphasize a seemingly intractable conflict between religious and secular ways of
being. This article takes a different approach, focusing instead on the space
that Witness patients have carved out for their accommodation in a major
pediatric research hospital. Using discourse analysis and interview data, I map
the way moralizing discourses surrounding Witness families have shifted over the
past 70 years alongside advancements in bloodless medicine. I argue that
Witnesses have helped to enable their present accommodation and recognition by
marshaling particular forms of economic, human, and social capital, and consider
whether their success might be attainable by other treatment-resisting patient
groups. Thus, this article explores the shifting limits of multicultural
accommodation and the conditions that make understanding, collaboration, and
compromise possible.
PMID- 28705098
TI - Prevention of systemic toxicity in hyperthermic isolated lung perfusion using
radioisotopic leakage monitoring.
AB - RATIONALE: Hyperthermic isolated lung Perfusion (ILuP) is used to deliver high
dose chemotherapy to pulmonary metastases while sparing systemic toxicity.
Accurate leakage monitoring is however necessary. This study aimed to verify the
accuracy of radionuclide leakage monitoring in patients undergoing ILuP, by
comparing this method with serial blood sampling. METHODS: A total of 15
consecutive ILuP procedures were performed on eleven patients affected by lung
metastases from soft tissue sarcoma. After establishing isolated perfusion,
erythrocytes of systemic blood (SB) were labelled with 0.2 MBq/kg of 99mTc. The
baseline SB counting rate (CR) was assessed using a gamma-probe. Subsequently,
erythrocytes of the circuit blood (CB) were labelled with 2 Mbq/kg of 99mTc.
Radioactivity leakage factor (RLF) was continuously measured using a formula,
accounting for CR, systemic/circuit activity ratio and total/systemic volume
ratio. The TNF-alpha concentration in SB and CB was measured by enzymelinked
immunosorbent assay (ELISA) throughout the procedure. RESULTS: RLF averaged 2.3
+/- 1.5%, while the systemic/circuit TNF-alpha ratio was 0.05 +/- 0.12%. These
two indices were strictly correlated in all of the procedures (average Rvalue
0.88 +/- 0.07). RLF exceeded 5% during three of 15 procedures, prompting the
application of compensatory manoeuvres. ELISA confirmed a marked increase in
systemic TNF-alpha levels in these patients (2.6 +/- 3.5 ng/ml). Conversely,
patients whose RLF did not exceed the 5% threshold presented a mean TNF-alpha of
0.02 +/- 0.005 ng/ml (p < 0.01). CONCLUSIONS: In patients submitted to ILuP, RLF
monitoring is feasible and accurate. Moreover, it grants immediate results,
permitting for the adoption of corrective manoeuvres for leakage, thus minimising
toxicity.
PMID- 28705099
TI - Heat-induced BRCA2 degradation in human tumours provides rationale for
hyperthermia-PARP-inhibitor combination therapies.
AB - PURPOSE: Hyperthermia (40-44 degrees C) effectively sensitises tumours to
radiotherapy by locally altering tumour biology. One of the effects of heat at
the cellular level is inhibition of DNA repair by homologous recombination via
degradation of the BRCA2-protein. This suggests that hyperthermia can expand the
group of patients that benefit from PARP-inhibitors, a drug exploiting homologous
recombination deficiency. Here, we explore whether the molecular mechanisms that
cause heat-mediated degradation of BRCA2 are conserved in cell lines from various
origins and, most importantly, whether, BRCA2 protein levels can be attenuated by
heat in freshly biopted human tumours. EXPERIMENTAL DESIGN: Cells from four
established cell lines and from freshly biopsied material of cervical (15), head-
and neck (9) or bladder tumours (27) were heated to 42 degrees C for 60 min ex
vivo. In vivo hyperthermia was studied by taking two biopsies of the same breast
or cervical tumour: one before and one after treatment. BRCA2 protein levels were
measured by immunoblotting. RESULTS: We found decreased BRCA2-levels after
hyperthermia in all established cell lines and in 91% of all tumours treated ex
vivo. For tumours treated with hyperthermia in vivo, technical issues and intra
tumour heterogeneity prevented obtaining interpretable results. CONCLUSIONS: This
study demonstrates that heat-mediated degradation of BRCA2 occurs in tumour
material directly derived from patients. Although BRCA2-degradation may not be a
practical biomarker for heat deposition in situ, it does suggest that application
of hyperthermia could be an effective method to expand the patient group that
could benefit from PARP-inhibitors.
PMID- 28705100
TI - Barriers to postpartum contraception: differences among women based on parity and
future fertility desires.
AB - Timely use of contraception in the postpartum year is critical for pregnancy
spacing, which protects a mother's health and improves her ability to care for
children. This qualitative study explored contraceptive decision-making among
postpartum women in Nairobi, Kenya, with a focus on accounts of how women
overcame barriers to postpartum contraceptive use. Focus groups (n = 61) and in
depth interviews (n = 30) explored experiences, barriers and actual use of
postpartum contraception. Data were analysed using framework analysis, a method
that organises qualitative data into themes and then interprets the data by
mapping participant characteristics to these themes. Contraceptive use among
women who desired future fertility was hindered by fear of side-effects and
concern for partner disapproval. However, women who were satisfied with their
family size more easily overcame these barriers. Tailoring postpartum
contraceptive counselling to both assuage the concerns of women who desire future
fertility and address the long-term contraceptive needs of mothers who desire to
stop child-bearing could play a role in reducing the unmet need for
contraception. .
PMID- 28705101
TI - Abdominal Wall Expanding System Obviates the Need for Lateral Release in Giant
Incisional Hernia and Laparostoma.
AB - BACKGROUND: In large incisional hernias and after laparostoma midline closure may
be impossible. A novel abdominal wall expander system (AWEX) is proposed and
evaluated. METHODS: In patients with large incisional hernias and laparostoma
where primary midline closure was impossible, AWEX was used. Patients undergoing
abdominal wall reconstruction using AWEX between May 2012 and December 2015 were
included. Intraoperative the abdominal wall was stretched by attaching the
midline fascia borders to a retraction system under tension for 30 minutes.
Length and width of the hernia defect were measured in preoperative computed
tomography. Width gain after AWEX procedure, operative time, morbidity, and
presence of remaining midline gap was evaluated. Patients were followed for
hernia recurrence. RESULTS: Ten patients with incisional hernias (N = 4) and
grafted laparostoma (N = 6) underwent abdominal wall reconstruction using AWEX.
Median (interquartile range) length and width of the hernia defect was 18.0 (15.0
20.5) and 12.0 (11.8-13.3) cm. Width gain after AWEX was 8.5 (8.0-10.5) cm.
Operative time was 270 (135-379) minutes. The major morbidity was 20%. In 4
patients a gap of 4 (4-5) cm was bridged by intraperitoneal onlay mesh. After a
median follow-up of 21 (7-36) months no hernia recurrence was observed.
CONCLUSIONS: Stretching of the abdominal wall that has been shown successful
using progressive restressed retention sutures and progressive preoperative
pneumoperitoneum is reduced from days and weeks to 30 minutes in AWEX. AWEX is a
promising alternative to component separation in repair of large incisional
hernias. After refinement of the system prospective evaluation is required.
PMID- 28705102
TI - Affective Evaluation of One's Own and Others' Body Odor: The Role of Disgust
Proneness.
AB - Disgust is part of a behavioral immune system that helps to detect pathogens. One
important input to this system is the sense of smell. We conducted an experiment
on body odor perception with 72 participants (35 men, 37 women; mean age = 24
years), who had been divided according to high versus low disgust proneness. All
participants were exposed to six samples of axillary sweat from other individuals
and to their own sweat. They were asked to identify their own body odor and to
rate their affective experience. The participants were not able to identify their
own sweat; however, differentiation of self versus others was based on
experienced disgust; the sweat of others was perceived as more disgusting.
Moreover, disgust-prone participants showed differential affective responses to
the two sweat sources and evaluated others' sweat as more negative and arousing.
The current study points to the important role of state/trait disgust in the
implicit processing of body odor.
PMID- 28705103
TI - Mother-child emotion dialogues: the disrupting effect of maternal history of
communal sleeping.
AB - The study examined associations between mothers' upbringing background (kibbutz
vs. home) and maternal-sensitive guidance of emotional conversations with their
preschool children; children's cooperation and exploration; and the coherence of
their conversations. Using a quasi-experimental design, 112 children and their
mothers (72 kibbutz raised, 40 home) completed the Autobiographical Emotional
Event Dialogue. We hypothesized that maternal kibbutz upbringing would be
associated to lower levels of mothers' sensitive guidance of the conversations,
children's lower cooperation and exploration, and lower overall coherence.
Results showed no upbringing-related differences for the mothers, but significant
differences were found for the children, with children of kibbutz-raised mothers
showing less cooperation and exploration, and lower levels of coherence for these
dyads. The role of maternal background in shaping the interaction with their
child is discussed.
PMID- 28705104
TI - Asymptomatic giant right atrial appendage aneurysm: a 7-year follow-up.
PMID- 28705105
TI - Clinical outcomes of secondary prevention strategies for young patients with
cryptogenic stroke and patent foramen ovale.
AB - Background The aim of this study was to compare the immediate and long-term
clinical outcomes of medical therapy and percutaneous patent foramen ovale (PFO)
closure as secondary prevention strategies in patients younger than 55 years of
age presenting with cryptogenic stroke and PFO. Methods Between January 2006 and
April 2015, all patients with the diagnosis of cryptogenic stroke and PFO were
analysed and prospectively followed. Stroke was confirmed in 159 out of 309
patients (51%). In the remaining cases, other neurological conditions were found
and therefore excluded from further analysis. Patients received PFO closure or
medical therapy on the basis of a pre-specified algorithm. Primary outcome was
the assessment of recurrent ischaemic events at follow-up. Results Percutaneous
PFO closure was performed in 77 patients (48%) and 82 (52%) were treated
medically. Mean follow-up was 51.6 +/- 34.8 months. Two ischaemic strokes
occurred in the medical group only (2.4% vs 0%; P = 0.16) and no complications
related to the invasive procedure were observed. Conclusions The diagnosis of
stroke in patients with PFO could be confirmed in 50% of cases only, underlining
the importance of a multidisciplinary evaluation of these patients. A very low
ischaemic recurrence rate was observed in the medical therapy group, suggesting
that a personalized treatment based on a prespecified diagnostic algorithm yields
good clinical results irrespective of the treatment modality. Given the low
number of recurrences, larger cohorts may be needed to prove significant
differences.
PMID- 28705106
TI - Characteristic features of patients with multiple accessory pathways.
AB - Objective Only limited clinical and electrophysiological data concerning patients
(pts) with multiple accessory pathways (MAP) in comparison to large control
groups are available. The aim of our study was to analyse these data from the
largest cohort of patients with multiple accessory pathways and a large control
group. Method and results We analysed data from pts with MAP (group 1) and pts
with a single accessory pathway (AP) (group 2) referred for radiofrequency
catheter ablation (RFCA) at our tertiary centre. Group 1 consisted of 124 pts (M
62.10%, mean age 33.00 +/- 5.26) with MAP and RFCA. Group 2 consisted of 376 pts
(M 51.20%, mean age 35.87 +/- 16.15) with a single accessory pathway and RF
ablation. Group 1 exhibited a higher incidence of overt APs (P < 0.0001), Ebstein
anomaly (P = 0.001), ventricular fibrillation (P = 0.012), antidromic
atrioventricular re-entrant tachycardia (A AVRT) (P = 0.025) and male gender (P =
0.038). The mean age at the first documented atrioventricular re-entrant
tachycardia (AVRT) episode was lower in pts with MAP than in pts with single APs:
16.79 +/- 13.41 vs 20.84 +/- 14.29, respectively (P = 0.001). Concealed accessory
pathways (P < 0.0001) occurred more frequently in the control group. Group 1 had
more right-lateral (P = 0.0001), mid-septal (P = 0.0001), left-posterior (P =
0.01), left-anterior (P = 0.013) and left-lateral localizations of AP (P <
0.037). Conclusions The MAP group included statistically significantly more men,
Ebstein anomaly and overt APs. The mean age of the first episode of
atrioventricular re-entrant tachycardia was lower in pts with MAP. Certain
distribution patterns are apparent for single and MAP. Pts with MAP are at higher
risk of VF and antidromic atrioventricular re-entrant tachycardia.
PMID- 28705107
TI - The systematic coronary risk evaluation (SCORE) for the prevention of
cardiovascular diseases. Does evidence exist for its effectiveness? A systematic
review.
AB - OBJECTIVES: The SCORE model predicts the ten-year risk of cardiovascular
mortality but it is still unknown whether applying the SCORE in clinical practice
subsequently improves cardiovascular disease (CVD) outcomes. The objective of
this study is to assess the effect of total cardiovascular risk estimation using
the SCORE in preventing serious cardiovascular events in European adults without
prior CVD. METHODS AND RESULTS: Data sources: eight bibliographical databases
(2003 - August 2015), other internet sources and reference lists of articles were
checked. This was supplemented by contact with the board members of the European
Society of Cardiology (ESC) and the authors of the SCORE model. STUDY ELIGIBILITY
CRITERIA: all prospective studies in any language investigating the effect of
using the SCORE on the clinical outcome (CVD death, major events and adverse
outcomes) in an adult population were examined. Two reviewers assessed the
studies independently (titles, abstracts, full texts). After removal of
duplicates, 5,256 records were screened and 14 full text papers considered. No
eligible studies were identified. An extensive literature search revealed no
randomized control trial or other prospective study comparing significant
clinical outcomes between groups that used the SCORE and those who did not.
CONCLUSIONS: The effect of using the SCORE (with or without subsequent
intervention) on CVD death, all-cause mortality, major CVD events like myocardial
infarction and stroke, as well as adverse outcomes, is still unknown. A cluster
randomised controlled trial is warranted to evaluate the use of the SCORE on
important outcomes.
PMID- 28705108
TI - Symptomatic double aortic arch in an adult patient.
PMID- 28705109
TI - Needles.
PMID- 28705110
TI - An unusual indication for subcutaneous implantable -cardioverter/defibrillator.
PMID- 28705111
TI - Use of portable ladders - field observations and self-reported safety performance
in the cable TV industry.
AB - Portable ladders incidents remain a major cause of falls from heights. This study
reported field observations of environments, work conditions and safety behaviour
involving portable ladders and their correlations with self-reported safety
performance. Seventy-five professional installers of a company in the cable and
other pay TV industry were observed for 320 ladder usages at their worksites. The
participants also filled out a questionnaire to measure self-reported safety
performance. Proper setup on slippery surfaces, correct method for ladder
inclination setup and ladder secured at the bottom had the lowest compliance with
best practices and training guidelines. The observation compliance score was
found to have significant correlation with straight ladder inclined angle
(Pearson's r = 0.23, p < 0.0002) and employees' self-reported safety
participation (r = 0.29, p < 0.01). The results provide a broad perspective on
employees' safety compliance and identify areas for improving safety behaviours.
Practitioner Summary: A checklist was used while observing professional
installers of a cable company for portable ladder usage at their worksites. Items
that had the lowest compliance with best practices and training guidelines were
identified. The results provide a broad perspective on employees' safety
compliance and identify areas for improving safety behaviours.
PMID- 28705112
TI - PCL-TCP wet spun scaffolds carrying antibiotic-loaded microspheres for bone
tissue engineering.
AB - Scaffolds produced for tissue engineering applications are proven to be promising
alternatives to be used in healing and regeneration of injured tissues and
organs. In this study, porous and fibrous poly(epsilon-caprolactone) (PCL)
scaffolds were prepared by wet spinning technique and modified by addition of
tricalcium phosphate (TCP) and by immobilizing gelatin onto fibers. Meanwhile,
gelatin microspheres carrying Ceftriaxone sodium (CS), a model antibiotic, were
added onto the scaffolds and antimicrobial activity of CS was investigated
against Escherichia coli (E. coli), a model gram-negative bacterium. TCP and
gelatin were added to enhance mechanical properties while directing the scaffold
towards osteogenic infrastructure and to increase hydrophilicity by activating
cell attachment via protein molecules, respectively. Modifications with TCP and
gelatin enhanced the compression modulus by about 70%, and attachment of Saos-2
cells by 60%, respectively. Release of the antibiotic demonstrated effective
antimicrobial activity against E. coli. The bioactive scaffolds were shown to be
good candidates for bone tissue engineering applications.
PMID- 28705113
TI - EGFL7 participates in regulating biological behavior of growth hormone-secreting
pituitary adenomas via Notch2/DLL3 signaling pathway.
AB - Growth hormone-secreting pituitary adenoma accounts for about 20% of the third
most common intracranial neoplasm-pituitary adenomas-which makes up 15% of all
intracranial tumors. The growth hormone-secreting pituitary adenoma invasion is a
key risk factor associated with the operation results and highly correlated with
the clinical prognosis. The epidermal growth factor-like domain multiple 7
protein, a unique 29 kDa secreted angiogenic factor, can result in pathologic
angiogenesis and enhance the tumor migration and invasion. In this study, for the
first time we found that epidermal growth factor-like domain multiple 7 protein
expression was markedly higher in invasive growth hormone-secreting pituitary
adenoma than non-invasive growth hormone-secreting pituitary adenoma. The tumor
volume, histologic subtypes, invasiveness and recurrence of growth hormone
secreting pituitary adenoma were significantly associated with epidermal growth
factor-like domain multiple 7 protein expression. Furthermore, we discovered that
the histological classification methods of growth hormone-secreting pituitary
adenoma according to electron microscopic examination and biological marker
classification methods according to epidermal growth factor-like domain multiple
7 protein expression are more valuable in clinical application than the
traditional classification methods based on Knosp and Hardy-Wilson grades. In
summary, our results indicated epidermal growth factor-like domain multiple 7
protein participates in growth hormone-secreting pituitary adenoma proliferation
and invasion regulation via Notch2/DLL3 signaling pathway. These findings raised
the possibility that epidermal growth factor-like domain multiple 7 protein might
serve as a useful biomarker to assess growth hormone-secreting pituitary adenoma
invasion and prognosis or a potential therapeutic target for growth hormone
secreting pituitary adenoma treatment.
PMID- 28705114
TI - Genetic changes of MLH1 and MSH2 genes could explain constant findings on
microsatellite instability in intracranial meningioma.
AB - Postreplicative mismatch repair safeguards the stability of our genome. The
defects in its functioning will give rise to microsatellite instability. In this
study, 50 meningiomas were investigated for microsatellite instability. Two major
mismatch repair genes, MLH1 and MSH2, were analyzed using microsatellite markers
D1S1611 and BAT26 amplified by polymerase chain reaction and visualized by gel
electrophoresis on high-resolution gels. Furthermore, genes DVL3 (D3S1262), AXIN1
(D16S3399), and CDH1 (D16S752) were also investigated for microsatellite
instability. Our study revealed constant presence of microsatellite instability
in meningioma patients when compared to their autologous blood DNA. Altogether
38% of meningiomas showed microsatellite instability at one microsatellite locus,
16% on two, and 13.3% on three loci. The percent of detected microsatellite
instability for MSH2 gene was 14%, and for MLH1, it was 26%, for DVL3 22.9%, for
AXIN1 17.8%, and for CDH1 8.3%. Since markers also allowed for the detection of
loss of heterozygosity, gross deletions of MLH1 gene were found in 24% of
meningiomas. Genetic changes between MLH1 and MSH2 were significantly positively
correlated (p = 0.032). We also noted a positive correlation between genetic
changes of MSH2 and DVL3 genes (p = 0.034). No significant associations were
observed when MLH1 or MSH2 was tested against specific histopathological
meningioma subtype or World Health Organization grade. However, genetic changes
in DVL3 were strongly associated with anaplastic histology of meningioma (chi2 =
9.14; p = 0.01). Our study contributes to better understanding of the genetic
profile of human intracranial meningiomas and suggests that meningiomas harbor
defective cellular DNA mismatch repair mechanisms.
PMID- 28705115
TI - MicroRNA-21 versus microRNA-34: Lung cancer promoting and inhibitory microRNAs
analysed in silico and in vitro and their clinical impact.
AB - MicroRNAs are well-known strong RNA regulators modulating whole functional units
in complex signaling networks. Regarding clinical application, they have
potential as biomarkers for prognosis, diagnosis, and therapy. In this review, we
focus on two microRNAs centrally involved in lung cancer progression. MicroRNA-21
promotes and microRNA-34 inhibits cancer progression. We elucidate here involved
pathways and imbed these antagonistic microRNAs in a network of interactions,
stressing their cancer microRNA biology, followed by experimental and
bioinformatics analysis of such microRNAs and their targets. This background is
then illuminated from a clinical perspective on microRNA-21 and microRNA-34 as
general examples for the complex microRNA biology in lung cancer and its
diagnostic value. Moreover, we discuss the immense potential that microRNAs such
as microRNA-21 and microRNA-34 imply by their broad regulatory effects. These
should be explored for novel therapeutic strategies in the clinic.
PMID- 28705116
TI - Alex3 suppresses non-small cell lung cancer invasion via AKT/Slug/E-cadherin
pathway.
AB - Alex3, is a newly identified mitochondrial protein, regulates mitochondrial
dynamics and is involved in neural development. However, its expression pattern
and clinicopathological relevance in human tumors are still unclear. In this
study, Immunohistochemistry assay was performed in 109 cases of lung cancer
samples and found that Alex 3 expression in lung cancer tissues was significantly
lower than adjacent normal lung tissues (28.4% vs 52.6%, p < 0.001). Sequent
statistical analysis indicated that negative Alex3 expression was significantly
associated with advanced tumor-node-metastasis stages (p = 0.001), positive lymph
node metastasis (p = 0.005), and poor prognosis (p = 0.008). After overexpression
of Alex3, levels of p-AKT and Slug were downregulated, while level of E-cadherin
was upregulated, which results in the inhibition of invasion and migration
ability of lung cancer cells. In conclusion, reduction of Alex3 correlates with
the development of non-small cell lung cancer and predicts adverse clinical
outcome of non-small cell lung cancer patients. The effect of Alex3 on inhibiting
invasion and migration may attribute to upregulation of E-cadherin expression
through AKT-Slug pathway inactivation.
PMID- 28705117
TI - MicroRNA-25 suppresses proliferation, migration, and invasion of osteosarcoma by
targeting SOX4.
AB - Altered expression of the miR-25 has been implicated in many human malignant
progression as oncogene or tumor suppressor. However, the precise role of miR-25
in osteosarcoma progression remains largely unclear. This study aimed to
investigate the role and underlying mechanism of miR-25 in osteosarcoma. In this
study, we demonstrated that miR-25 was significantly downregulated in
osteosarcoma cell lines and tissues and that lower miR-25 was associated with
advanced tumor-node-metastasis stage and lymph node metastasis. Then, we found
that introduction of miR-25 significantly suppressed the proliferation, colony
formation, migration, and invasion of osteosarcoma cells in vitro and retarded
tumor growth in vivo. Further studies indicated that the epithelial-mesenchymal
transition-related transcription factor, SOX4 (SRY-related high-mobility group
box 4), was a direct target gene of miR-25, evidenced by bioinformatics analysis
predicted and luciferase reporter assay. Furthermore, miR-25 could decrease the
expression of SOX4 levels and inhibited epithelial-mesenchymal transition
process. The levels of miR-25 were inversely correlated with those of SOX4
expression in osteosarcoma tissues. SOX4 overexpression rescued miR-25-induced
suppression of proliferation, migration, and invasion of osteosarcoma cells.
Taken together, these results suggest that miR-25 functions as a tumor suppressor
in the progression of osteosarcoma by repressing SOX4.
PMID- 28705118
TI - Curcumin inhibits bladder cancer progression via regulation of beta-catenin
expression.
AB - Bladder cancer has a considerable morbidity and mortality impact with
particularly poor prognosis. Curcumin has been recently noticed as a polyphenolic
compound separated from turmeric to regulate tumor progression. However, the
precise molecular mechanism by which curcumin inhibits the invasion and
metastasis of bladder cancer cells is not fully elucidated. In this study, we
investigate the effect of curcumin on the bladder cancer as well as possible
mechanisms of curcumin. The expression of beta-catenin was detected by
quantitative real-time polymerase chain reaction and immunohistochemical analysis
in a series of bladder cancer tissues. In addition, bladder cancer cell lines T24
and 5637 cells were treated with different concentrations of curcumin. The
cytotoxic effect of curcumin on cell proliferation of T24 and 5637 cells was
measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay.
The migration and invasion capacity of T24 and 5637 cells were measured by
transwell assay. The effects of curcumin on expression levels of beta-catenin and
epithelial-mesenchymal transition marker were determined by western blotting. The
beta-catenin expression was significantly upregulated in bladder cancer tissues
when compared with corresponding peri-tumor tissues. Furthermore, curcumin
inhibited the cell proliferation of T24 and 5637 cells, and curcumin reduced the
migration and invasive ability of T24 and 5637 cells via regulating beta-catenin
expression and reversing epithelial-mesenchymal transition. Curcumin may be a new
drug for bladder cancer.
PMID- 28705119
TI - Can stories reduce abortion stigma? Findings from a longitudinal cohort study.
AB - Women often hide or selectively disclose abortion experiences due to stigma.
Secrecy can help women avoid stigma but may also result in isolation and a lack
of social support and contribute to broader social silence. This study assesses
whether a book-club intervention can support abortion disclosure among book club
participants and improve participants' affective responses towards women who have
abortions and abortion providers. A total of 109 women from 13 all-female book
clubs located in 9 US states read and discussed a non-fiction book that included
stories about pregnancy and abortion, participated in a book club discussion and
completed baseline, immediate post-intervention and endline surveys. In 10 out of
the 13 book club discussions, at least one member disclosed having had a previous
abortion. Overall, 15 of the 19 women who privately reported having a previous
abortion self-disclosed one or more abortions during the book club discussion.
Following the book club intervention, women reported having more positive
feelings toward women who have abortions and abortion providers. Greater
improvement and longer lasting effects were seen in groups where there was also
an in-person disclosure of abortion experience. Findings suggest that exposure to
the stories of women who have had abortions can reduce abortion stigma.
PMID- 28705120
TI - QSAR, docking, ADMET, and system pharmacology studies on tormentic acid
derivatives for anticancer activity.
AB - To explore the anticancer compounds from tormentic acid derivatives, a
quantitative structure-activity relationship (QSAR) model was developed by the
multiple linear regression methods. The developed QSAR model yielded a high
activity-descriptors relationship accuracy of 94% referred by regression
coefficient (r2 = .94) and a high activity prediction accuracy of 91%. The QSAR
study indicates that chemical descriptors, chiV5, T_T_Cl_7, T_2_T_4, SsCH3count,
and Epsilon3 are significantly correlated with anticancer activity. This
validated model was further been used for virtual screening and thus
identification of new potential breast cancer inhibitors. Lipinski's rule of
five, ADMET risk and synthetic accessibility are used to filter false positive
hits. Filtered compounds were then docked to identify the possible target binding
pocket, to obtain a set of aligned ligand poses and to prioritize the predicted
active compounds. The scrutinized compounds, as well as their metabolites, were
predicted and analyzed for different pharmacokinetics parameters such as
absorption, distribution, metabolism, excretion, and toxicity. Finally, the top
ranked compound NB-12 was evaluated by system pharmacology approach. Later
studied the metabolic networks, disease biomarker networks, pathway maps, drug
target networks and generate significant gene networks. The strategy applied in
this research work may act as a framework for rational design of potential
anticancer drugs.
PMID- 28705121
TI - Greenlandic patients with colorectal cancer: symptomatology, primary
investigations and differences in diagnostic intervals between Nuuk and the rest
of the country.
AB - BACKGROUND: Colorectal cancer (CRC) is a potentially fatal disease, and expedited
referral and treatment is needed to ensure early detection. OBJECTIVE: We aimed
to assess the symptomatology of Greenlandic patients with CRC and the primary
investigations initiated before referral to Dronning Ingrids Hospital in Nuuk for
further diagnostic workup. Primary care interval (first consultation until
referral), hospital interval (referral until diagnosis) and diagnostic interval
(first consultation until diagnosis) were calculated and compared between
patients living in Nuuk and in other places in Greenland ("the Coast"). DESIGN:
This was a retrospective, register-based study of all patients in Greenland
diagnosed with CRC from 2008 through 2011. Medical history was obtained and
investigated by reviewing the primary care charts. RESULTS: In total 113 patients
were identified from the Greenlandic cancer database or pathology reports. About
80% of the patients were asked about blood in the stools and changes of bowel
habits, and the majority responded positively to this. Abdominal examination was
performed for 78%, 65% had a rectal examination performed, 22% a proctoscopy
performed and 51% a haemoglobin level measured. The median primary care interval
was 4 days in Nuuk vs. 55 days for patients from "the Coast" (p=0.01); the median
diagnostic interval was 55 days in Nuuk vs. 95 days for patients from "the Coast"
(p=0.04). Median hospital interval was similar for both groups (23 days vs 24
days; p=0.86). Women had a median primary care interval of 70 days vs. 15 days
for men (p=0.06). CONCLUSIONS: Patients with CRC presented classic symptomatology
of CRC. Primary care interval and diagnostic interval were significantly longer
for patients from "the Coast" compared with Nuuk. Women tended to have longer
primary care interval. A more standardised examination should be implemented and
a national CRC screening programme should be considered to reduce the difference
in diagnostic interval and ensure timely referral.
PMID- 28705122
TI - The effect of using mobile applications for improving oral hygiene in patients
with orthodontic fixed appliances: a randomised controlled trial.
AB - OBJECTIVE: To investigate the effect of using mobile applications active
reminders to improve oral hygiene in comparison to verbal oral hygiene
instructions. DESIGN: Two-arm parallel randomised controlled trial. SETTING:
orthodontic clinics at two branches of a university hospitals of the college of
dentistry of Riyadh Colleges of Dentistry and Pharmacy, Riyadh, Saudi Arabia.
PARTICIPANTS: Forty-four 12-year-old and older subjects. METHOD: Subjects
undergoing orthodontic treatment with fixed appliances were randomly assigned to
one of two groups using simple randomisation. Group I: subjects received a mobile
application that sends active reminders of oral hygiene three times a day (n =
22). Group II: subjects received verbal oral hygiene instructions verbally during
their routine orthodontic visits (n = 22). Two primary outcomes were assessed
using plaque index (PI) and gingival index (GI) for Ramfjord teeth to evaluate
the level of oral hygiene at baseline and after 4 weeks. RESULTS: Mean
differences for PI and GI for group I were reduced from T1 to T2 (P < 0.05, P <
0.05) but did not significantly change for group II (P > 0.05, P > 0.05). Both PI
and GI significantly reduced for group I compared to group II between T1 and T2
(P < 0.05, P < 0.05). CONCLUSIONS: PI and GI all significantly decreased after 4
weeks of using active reminders of oral hygiene instructions on mobile
application compared to verbal oral hygiene instructions. The study was
registered at clinicaltrials.gov with number: NCT03109769.
PMID- 28705123
TI - Surgery of patellar fractures using a medial parapatellar approach.
AB - PURPOSE: The general surgical approach for patellar fractures has a significant
weakness, in that the articular facet is invisible because the fixation is
performed using radiation amplifiers after exposing the fracture site through
vertical or transverse dissection on the anterior patella. We report excellent
outcomes in the surgical treatment of patellar fractures, using a medial
parapatellar approach. METHODS: This study evaluated 20 patients who underwent
surgery between August 2008 and April 2014 to correct patellar fractures with
comminution or with displacement of the articular facet of >=2 mm and who had >=1
year of follow-up. Surgery was performed using anatomical reduction with direct
exposure of the articular facet of the patella via a medial parapatellar
approach. Bone union, severity of displacement, range of motion (ROM) of the
patella, and complications were evaluated after surgery, and patellar function
was evaluated using the Lysholm knee score. RESULTS: Bone union was achieved in
all cases, and average displacement of the articular facet decreased from 3.2 mm
(range: 1.2-7.3 mm) preoperatively to 0.2 mm (range: 0-0.5 mm) postoperatively.
No particular postsurgical complication was observed. All cases had a normal ROM,
and the average Lysholm score at final follow-up was 96.2 points. CONCLUSION:
Anatomical fixation of the articular facet via a medial parapatellar approach
appears to be suitable for patellar fractures, which are intra-articular.
PMID- 28705124
TI - The accuracy and safety of fluoroscopic-guided percutaneous pedicle screws in the
thoracic and lumbosacral spine in the Asian population: A CT scan analysis of
1002 screws.
AB - PURPOSE: This study investigates the safety and accuracy of percutaneous pedicle
screws placed using fluoroscopic guidance in the thoracolumbosacral spine among
Asian patients. METHODS: Computerized tomography scans of 128 patients who had
surgery using fluoroscopic-guided percutaneous pedicle screws were selected.
Medial, lateral, superior, and inferior screw perforations were classified into
grade 0 (no violation), grade 1 (<2 mm perforation), grade 2 (2-4 mm
perforation), and grade 3(>4 mm perforation). Anterior perforations were
classified into grade 0 (no violation), grade 1 (<4 mm perforation), grade 2 (4-6
mm perforation), and grade 3(>6 mm perforation). Grade 2 and grade 3 perforation
were considered as "critical" perforation. RESULTS: In total, 1002 percutaneous
pedicle screws from 128 patients were analyzed. The mean age was 52.7 +/- 16.6.
There were 70 male patients and 58 female patients. The total perforation rate
was 11.3% (113) with 8.4% (84) grade 1, 2.6% (26) grade 2, and 0.3% (3) grade 3
perforations. The overall "critical" perforation rate was 2.9% (29 screws) and no
complications were noted. The highest perforation rates were at T4 (21.6%), T2
(19.4%), and T6 (19.2%). CONCLUSION: The total perforation rate of 11.3% with the
total "critical" perforation rate of 2.9% (2.6% grade 2 and 0.3% grade 3
perforations). The highest perforation rates were found over the upper to mid
thoracic region. Fluoroscopic-guided percutaneous pedicle screws insertion among
Asians has the safety and accuracy comparable to the current reported
percutaneous pedicle screws and open pedicle screws techniques.
PMID- 28705139
TI - Anaplastic lymphoma kinase (ALK) mutations in patients with adenocarcinoma of the
lung.
AB - BACKGROUND: Non-small cell lung cancer (NSCLC) is a major cause of cancer-related
death. Approximately 2-16% of NSCLC patients with wild-type epidermal growth
factor receptor (EGFR) harbour anaplastic lymphoma kinase (ALK) mutations. Both
EGFR and ALK mutations occur most commonly in Asian patients with NSCLC. As
targeted therapy is available for NSCLC patients with these mutations, it is
important to establish reliable assays and testing strategies to identify those
most likely to benefit from this therapy. MATERIALS AND METHODS: Patients
diagnosed with adenocarcinoma of the lung between 2010 and 2014 were tested for
EGFR mutations. Of these, 92 cases were identified as EGFR wild type and suitable
candidates for ALK testing utilising immunohistochemistry and the rabbit
monoclonal antibody D5F3. The reliability of the IHC was confirmed by validating
the results against those achieved by fluorescence in situ hybridisation (FISH)
to detect ALK gene rearrangements. RESULTS: Twelve (13%) cases were positive for
ALK expression using immunohistochemistry. Of the 18 evaluable cases tested by
FISH, there was 100% agreement with respect to ALK rearrangement/ALK expression
between the assays, with 11 cases ALK negative and 7 cases ALK positive by both
assays. ALK tumour expression was significantly more common in female compared to
male patients (29.6% vs. 6.2%, P < 0.001), detected exclusively in patients that
had never smoked (P < 0.001) and more frequently in metastases (22.7%) than in
primary tumours (10%) (P = 0.047). CONCLUSIONS: Detection of ALK expression by
IHC is reliable and the most practical way of identifying NSCLC patients likely
to benefit from crizotinib treatment.
PMID- 28705145
TI - Texture-based classification of different single liver lesion based on SPAIR T2W
MRI images.
AB - BACKGROUND: To assess the feasibility of texture analysis (TA) based on spectral
attenuated inversion-recovery T2 weighted magnetic resonance imaging (SPAIR T2W
MRI) for the classification of hepatic hemangioma (HH), hepatic metastases (HM)
and hepatocellular carcinoma (HCC). METHODS: The SPAIR T2W-MRI data of 162
patients with HH (n=55), HM (n=67) and HCC (n=40) were retrospectively analyzed.
We used two independent cohorts for training (n = 112 patients) and validation (n
= 50 patients). The TA was performed and textual parameters derived from the gray
level co-occurrence matrix (GLCM), gray level gradient co-occurrence matrix
(GLGCM), gray-level run-length matrix (GLRLM), Gabor wavelet transform (GWTF),
intensity-size-zone matrix (ISZM), and histogram features were calculated. The
capacity of each parameter to classify three types of single liver lesions was
assessed using the Kruskal-Wallis test. Specificity and sensitivity for each of
the studied parameters were derived using ROC curves. Four supervised
classification algorithms were trained with the most influential textural
features in the classification of tumor types. The test datasets validated the
reliability of the models. RESULTS: The texture analyses showed that the HH
versus HM, HM versus HCC, and HH versus HCC could be differentiated by 9, 16 and
10 feature parameters, respectively. The model's misclassification rates were
11.7, 9.6 and 9.7% respectively. No texture feature was able to adequately
distinguish among the three types of single liver lesions at the same time. The
BP-ANN model had better predictive ability. CONCLUSION: Texture features of SPAIR
T2W-MRI can classify the three types of single liver lesions (HH, HM and HCC) and
may serve as an adjunct tool for accurate diagnosis of these diseases.
PMID- 28705146
TI - Satisfaction with caregivers during labour among low risk women in the
Netherlands: the association with planned place of birth and transfer of care
during labour.
AB - BACKGROUND: The caregiver has an important influence on women's birth
experiences. When transfer of care during labour is necessary, care is handed
over from one caregiver to the other, and this might influence satisfaction with
care. It is speculated that satisfaction with care is affected in particular for
women who need to be transferred from home to hospital. We examined the level of
satisfaction with the caregiver among women with planned home versus planned
hospital birth in midwife-led care. METHODS: We used data from the prospective
multicentre DELIVER (Data EersteLIjns VERloskunde) cohort-study, conducted in
2009 and 2010 in the Netherlands. Women filled in a postpartum questionnaire
which contained elements of the Consumer Quality index. This instrument measures
'general rate of satisfaction with the caregiver' (scale from 1 to 10, with cut
off of below 9) and 'quality of treatment by the caregiver' (containing 7 items
on a 4 point Likert scale, with cut-off of mean of 4 or lower). RESULTS: Women
who planned a home birth (n = 1372) significantly more often rated 'quality of
treatment by caregiver' high than women who planned a hospital birth (n = 829).
Primiparous women who planned a home birth significantly more often had a high
rate (9 or 10) for 'general satisfaction with caregiver' (adj.OR 1.48; 95% CI
1.1, 2.0). Also, primiparous women who planned a home birth and had care
transferred during labour (331/553; 60%) significantly more often had a high rate
(9 or 10) for 'general satisfaction' compared to those who planned a hospital
birth and who had care transferred (1.44; 1.0-2.1). Furthermore, they
significantly more often rated 'quality of treatment by caregiver' high, than
276/414 (67%) primiparous women who planned a hospital birth and who had care
transferred (1.65; 1.2-2.3). No differences were observed for multiparous women
who had planned home or hospital birth and who had care transferred. CONCLUSIONS:
Planning home birth is associated to a good experience of quality of care by the
caregiver. Transferred planned home birth compared to a transferred planned
hospital birth does not lead to a more negative experience of care received from
the caregiver.
PMID- 28705147
TI - Sample size re-estimation in paired comparative diagnostic accuracy studies with
a binary response.
AB - BACKGROUND: The sample size required to power a study to a nominal level in a
paired comparative diagnostic accuracy study, i.e. studies in which the
diagnostic accuracy of two testing procedures is compared relative to a gold
standard, depends on the conditional dependence between the two tests - the lower
the dependence the greater the sample size required. A priori, we usually do not
know the dependence between the two tests and thus cannot determine the exact
sample size required. One option is to use the implied sample size for the
maximal negative dependence, giving the largest possible sample size. However,
this is potentially wasteful of resources and unnecessarily burdensome on study
participants as the study is likely to be overpowered. A more accurate estimate
of the sample size can be determined at a planned interim analysis point where
the sample size is re-estimated. METHODS: This paper discusses a sample size
estimation and re-estimation method based on the maximum likelihood estimates,
under an implied multinomial model, of the observed values of conditional
dependence between the two tests and, if required, prevalence, at a planned
interim. The method is illustrated by comparing the accuracy of two procedures
for the detection of pancreatic cancer, one procedure using the standard battery
of tests, and the other using the standard battery with the addition of a PET/CT
scan all relative to the gold standard of a cell biopsy. Simulation of the
proposed method illustrates its robustness under various conditions. RESULTS: The
results show that the type I error rate of the overall experiment is stable using
our suggested method and that the type II error rate is close to or above
nominal. Furthermore, the instances in which the type II error rate is above
nominal are in the situations where the lowest sample size is required, meaning a
lower impact on the actual number of participants recruited. CONCLUSION: We
recommend multinomial model maximum likelihood estimation of the conditional
dependence between paired diagnostic accuracy tests at an interim to reduce the
number of participants required to power the study to at least the nominal level.
TRIAL REGISTRATION: ISRCTN ISRCTN73852054 . Registered 9th of January 2015.
Retrospectively registered.
PMID- 28705148
TI - Correlates of facility delivery for rural HIV-positive pregnant women enrolled in
the MoMent Nigeria prospective cohort study.
AB - BACKGROUND: Low rates of maternal healthcare service utilization, including
facility delivery, may impede progress in the prevention of mother-to-child
transmission of HIV (PMTCT) and in reducing maternal and infant mortality. The
MoMent (Mother Mentor) study investigated the impact of structured peer support
on early infant diagnosis presentation and postpartum maternal retention in PMTCT
care in rural Nigeria. This paper describes baseline characteristics and
correlates of facility delivery among MoMent study participants. METHODS: HIV
positive pregnant women were recruited at 20 rural Primary Healthcare Centers
matched by antenatal care clinic volume, client HIV prevalence, and PMTCT service
staffing. Baseline and delivery data were collected by participant interviews and
medical record abstraction. Multivariate logistic regression with generalized
estimating equation analysis was used to evaluate for correlates of facility
delivery including exposure to structured (closely supervised Mentor Mother,
intervention) vs unstructured (routine, control) peer support. RESULTS: Of 497
women enrolled, 352 (71%) were between 21 and 30 years old, 319 (64%) were
Christian, 245 (49%) had received secondary or higher education, 402 (81%) were
multigravidae and 299 (60%) newly HIV-diagnosed. Delivery data was available for
445 (90%) participants, and 276 (62%) of these women delivered at a health
facility. Facility delivery did not differ by type of peer support; however, it
was positively associated with secondary or greater education (aOR 1.9, CI 1.1
3.2) and Christian affiliation (OR 1.4, CI 1.0-2.0) and negatively associated
with primigravidity (OR 0.5; 0.3-0.9) and new HIV diagnosis (OR 0.6, CI 0.4-0.9).
CONCLUSIONS: Primary-level or lesser-educated HIV-infected pregnant women and
those newly-diagnosed and primigravid should be prioritized for interventions to
improve facility delivery rates and ultimately, healthy outcomes. Incremental
gains in facility delivery from structured peer support appear limited, however
the impact of duration of pre-delivery support needs further investigation.
Religious influences on facility delivery and on general maternal healthcare
service utilization need to be further explored. TRIAL REGISTRATION:
ClinicalTrials.gov number NCT01936753 , registered September 2013.
PMID- 28705149
TI - f-treeGC: a questionnaire-based family tree-creation software for genetic
counseling and genome cohort studies.
AB - BACKGROUND: The Tohoku Medical Megabank project aims to create a next-generation
personalized healthcare system by conducting large-scale genome-cohort studies
involving three generations of local residents in the areas affected by the Great
East Japan Earthquake. We collected medical and genomic information for
developing a biobank to be used for this healthcare system. We designed a
questionnaire-based pedigree-creation software program named "f-treeGC," which
enables even less experienced medical practitioners to accurately and rapidly
collect family health history and create pedigree charts. RESULTS: f-treeGC may
be run on Adobe AIR. Pedigree charts are created in the following manner: 1) At
system startup, the client is prompted to provide required information on the
presence or absence of children; f-treeGC is capable of creating a pedigree up to
three generations. 2) An interviewer fills out a multiple-choice questionnaire on
genealogical information. 3) The information requested includes name, age,
gender, general status, infertility status, pregnancy status, fetal status, and
physical features or health conditions of individuals over three generations. In
addition, information regarding the client and the proband, and birth order
information, including multiple gestation, custody, multiple individuals, donor
or surrogate, adoption, and consanguinity may be included. 4) f-treeGC shows only
marriages between first cousins via the overlay function. 5) f-treeGC
automatically creates a pedigree chart, and the chart-creation process is visible
for inspection on the screen in real time. 6) The genealogical data may be saved
as a file in the original format. The created/modified date and time may be
changed as required, and the file may be password-protected and/or saved in read
only format. To enable sorting or searching from the database, the file name
automatically contains the terms typed into the entry fields, including physical
features or health conditions, by default. 7) Alternatively, family histories are
collected using a completed foldable interview paper sheet named "f-sheet", which
is identical to the questionnaire in f-treeGC. CONCLUSIONS: We developed a
questionnaire-based family tree-creation software, named f-treeGC, which is fully
compliant with international recommendations for standardized human pedigree
nomenclature. The present software simplifies the process of collecting family
histories and pedigrees, and has a variety of uses, from genome cohort studies or
primary care to genetic counseling.
PMID- 28705150
TI - Economic burden of varicella in children 1-12 Years of age in Hungary, 2011-2015.
AB - BACKGROUND: Although live-attenuated varicella-zoster virus (VZV) vaccines have
been proven to be safe and effective in preventing varicella and real-word
evidence shows routine childhood immunization programs are effective in
dramatically reducing varicella associated morbidity and mortality, varicella
vaccine is not included in the National Immunization Program (NIP) in Hungary.
The purpose of this study was to evaluate the clinical and economic burden
associated with varicella in Hungary. METHODS: This was a multicenter,
retrospective, chart review study of patients aged 1-12 years with a primary
varicella diagnosis between 2011 and 2015. Healthcare resource utilization (HCRU)
associated with varicella, unit costs, and work loss were used to estimate direct
and indirect costs. All costs are presented in 2015 HUF / Euros (?). RESULTS: 156
children with varicella were included (75 outpatients, 81 inpatients), with a
mean age of 4.4 (SD: 2.0) and 3.7 (SD: 2.1) years, respectively. One or more
complications were reported by 12.0% of outpatients and 92.6% of inpatients, the
most common being dehydration, skin and soft tissue infections, pneumonia,
keratoconjunctivitis, and cerebellitis. HCRU estimates included use of over-the
counter (OTC) medications (96.0% outpatients, 53.1% inpatients), prescription
medications (9.3% outpatients, 70.4% inpatients), tests/procedures (4.0%
outpatients, 97.5% inpatients), and consultation with allied health professionals
(2.7% outpatients, 30.9% inpatients). The average duration of hospital stay
(inpatients) was 3.6 (95% CI: 3.2, 4.1) days. The total combined direct and
indirect cost per varicella case was 228,146.7 Hungarian Forint (HUF)/? 736.0 for
inpatients and 49,790.6 HUF/? 106.6 for outpatients. The overall annual cost of
varicella in Hungary for children aged <15 years in 2015 was estimated at
1,903,332,524.3 HUF/ ? 6,139,980.4. CONCLUSION: Varicella is associated with
substantial clinical burden in Hungary, resulting in the utilization of a
significant amount of healthcare resources. These results support the need for
routine vaccination of all healthy children to reduce the varicella-associated
disease burden.
PMID- 28705151
TI - Cost and yield considerations when expanding recruitment for genetic studies: the
primary open-angle African American glaucoma genetics study.
AB - BACKGROUND: African Americans have been historically under-represented in genetic
studies. More research is needed on effective recruitment strategies for this
population, especially on approaches that supplement traditional clinic
enrollment. This study evaluates the cost and efficacy of four supplemental
recruitment methods employed by the Primary Open-Angle African American Glaucoma
Genetics (POAAGG) study. METHODS: After enrolling 2304 patients from University
of Pennsylvania ophthalmology clinics, the POAAGG study implemented four new
recruitment methods to supplement clinic enrollment. These methods included: 1)
outreach in the local community, 2) in-house screening of community members ("in
reach"), 3) expansion to two external sites, and 4) sampling of the Penn Medicine
Biobank. The cost per subject was calculated for each method and enrollment among
cases, controls, and suspects was reported. RESULTS: The biobank offered the
lowest cost ($5/subject) and highest enrollment yield (n = 2073) of the four
methods, but provided very few glaucoma cases (n = 31). External sites provided
88% of cases recruited from the four methods (n = 388; $85/subject), but case
enrollment at these sites declined over the next 9 months as the pool of eligible
subjects was depleted. Outreach and in-reach screenings of community members were
very high cost for low return on enrollment ($569/subject for 102 subjects and
$606/subject for 45 subjects, respectively). CONCLUSIONS: The biobank offered the
most cost-effective method for control enrollment, while expansion to external
sites was necessary to recruit richly phenotyped cases. These recruitment methods
helped the POAAGG study to exceed enrollment of the discovery cohort (n = 5500) 6
months in advance of the predicated deadline and could be adopted by other large
genetic studies seeking to supplement clinic enrollment.
PMID- 28705152
TI - Elevated serum CEA levels are associated with the explosive progression of lung
adenocarcinoma harboring EGFR mutations.
AB - BACKGROUND: Serum carcinoembryonic antigen (CEA) levels are a predictor of
epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) efficacy
and are associated with epidermal growth factor receptor (EGFR) gene mutations.
However, the clinical significance of plasma CEA level changes during different
cycles of target therapy is unknown for lung adenocarcinoma patients with
sensitizing EGFR mutations. METHODS: In total, 155 patients with lung
adenocarcinoma were enrolled in this retrospective study between 2011 and 2015.
EGFR mutations were detected by RT-PCR (real-time quantitative PCR). Plasma CEA
levels were measured prior to different EGFR-TKI treatment cycles. Computed
tomography (CT) scans were conducted every 2 months to assess the therapeutic
efficacy. RESULTS: Serum CEA concentrations were significantly associated with
EGFR mutations (p < 0.05). Furthermore, in all patients treated with EGFR-TKIs,
the serum CEA levels increased with disease progression (p < 0.005). A COX
multivariate analysis revealed that CEA levels 16.2 times above normal were
associated with early disease progression (HR, 5.77; 95% CI:2.36 ~ 14.11; p <
0.001). Based on this finding, a threshold was set at the median time of 8.3
months. Patients with EGFR mutations exhibited a median progression-free survival
time of 12.8 months. Serum CEA levels were markedly increased compared to levels
measured 4.5 months prior to the changes detected via CT scans for patients
resistant to EGFR-TKIs. CONCLUSIONS: Elevated CEA levels during targeted therapy
may be a more sensitive predictor of explosive lung adenocarcinoma progression in
patients harboring mutant EGFRs compared to traditional imaging methods.
PMID- 28705153
TI - A randomized clinical pharmacokinetic trial of Tenofovir in blood, plasma and
urine in adults with perfect, moderate and low PrEP adherence: the TARGET study.
AB - BACKGROUND: Tenofovir disoproxil fumarate (TDF) is key component of pre-exposure
prophylaxis (PrEP) and antiretroviral therapy (ART) for HIV, but existing tools
to monitor drug adherence are often inaccurate. Detection of tenofovir (TFV) in
accessible biological samples, such as fingerprick blood, urine or oral fluid
samples could be a novel objective measure of recent TDF adherence. To measure
TFV concentrations associated with different levels of TDF adherence, we designed
a randomized clinical trial to assess the blood, urine and oral fluid
concentrations of TFV in adults with perfect, moderate and low drug adherence.
METHODS/DESIGN: A randomized, open-label, clinical pharmacokinetic study of
tenofovir in healthy adult volunteers without HIV or Hepatitis B infection in
Thailand. Consenting, eligible participants are randomized (1:1:1) among three
groups to receive a controlled number of TDF (300 mg) doses in a combination pill
with emtricitabine (FTC, 200 mg) for six weeks. Participants in Group 1 receive a
single TDF/FTC tablet once daily (Perfect adherence); Group 2 receive a single
TDF/FTC tablet 4 times/week (Moderate adherence); and Group 3 receive a single
TDF/FTC tablet 2 times/week (Low adherence). Blood, plasma, urine and oral fluid
samples are collected for drug measurement during three study phases: (i) initial
6-week treatment phase; (ii) intensive 24-h blood sampling phase after 6 weeks;
(iii) 4-week washout phase. Thirty adults with evaluable pharmacokinetic samples
(10 per group) will be enrolled [based on ensuring 25% precision in
pharmacokinetic parameter estimates]. Pre-dose drug concentrations during the
treatment phase will be descriptive and comparisons between groups performed
using a Kruskal-Wallis test. A non-compartmental pharmacokinetic analysis will be
performed on the intensive sampling data at Week 7 and the time course of TFV
washout in the difference biological matrices will be reported based on the
detected concentrations following drug cessation. DISCUSSION: The results of this
randomized trial will define the target concentration thresholds of TFV in blood,
urine and oral fluid that can distinguish between different levels of TDF
adherence. Such adherence 'benchmarks' can be applied to real-time drug testing
and novel point-of-care tests to identify individuals with poor PrEP or ART
adherence. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT03012607 .
PMID- 28705154
TI - Phenotypic and genomic comparison of Mycobacterium aurum and surrogate model
species to Mycobacterium tuberculosis: implications for drug discovery.
AB - BACKGROUND: Tuberculosis (TB) is caused by Mycobacterium tuberculosis and
represents one of the major challenges facing drug discovery initiatives
worldwide. The considerable rise in bacterial drug resistance in recent years has
led to the need of new drugs and drug regimens. Model systems are regularly used
to speed-up the drug discovery process and circumvent biosafety issues associated
with manipulating M. tuberculosis. These include the use of strains such as
Mycobacterium smegmatis and Mycobacterium marinum that can be handled in
biosafety level 2 facilities, making high-throughput screening feasible. However,
each of these model species have their own limitations. RESULTS: We report and
describe the first complete genome sequence of Mycobacterium aurum ATCC23366, an
environmental mycobacterium that can also grow in the gut of humans and animals
as part of the microbiota. This species shows a comparable resistance profile to
that of M. tuberculosis for several anti-TB drugs. The aims of this study were to
(i) determine the drug resistance profile of a recently proposed model species,
Mycobacterium aurum, strain ATCC23366, for anti-TB drug discovery as well as
Mycobacterium smegmatis and Mycobacterium marinum (ii) sequence and annotate the
complete genome sequence of this species obtained using Pacific Bioscience
technology (iii) perform comparative genomics analyses of the various surrogate
strains with M. tuberculosis (iv) discuss how the choice of the surrogate model
used for drug screening can affect the drug discovery process. CONCLUSIONS: We
describe the complete genome sequence of M. aurum, a surrogate model for anti
tuberculosis drug discovery. Most of the genes already reported to be associated
with drug resistance are shared between all the surrogate strains and M.
tuberculosis. We consider that M. aurum might be used in high-throughput
screening for tuberculosis drug discovery. We also highly recommend the use of
different model species during the drug discovery screening process.
PMID- 28705155
TI - What characterizes the work culture at a hospital unit that successfully
implements change - a correlation study.
AB - BACKGROUND: To successfully achieve change in healthcare, a balance between
technology and "people ware", the human recourses, is necessary. However, the
human aspect of the change implementation process has received less attention
than the technological issues. The aim was to explore the factors that
characterize the work culture in a hospital unit that successfully implemented
change compared with the factors that characterize the work culture of a hospital
unit with unsuccessful implementation. METHOD: The Systematizing Person-Group
Relations method was used for gathering and analyzing data to explore what
dominate the behavior in a particular work environment identifying challenges,
limitations and opportunities. This method applied six different dimensions, each
representing different behavior in a work culture: Synergy, Withdrawal,
Opposition, Dependence, Control and Nurture. We compared two different units at
the same hospital, one that successfully implemented change and one that was
unsuccessful. RESULTS: There were significant statistical differences between
healthcare personnel working at a unit that successfully implemented change
contrasted with the unit with unsuccessful implementation. These significant
differences were found in both the synergy and control dimensions, which are
important positive qualities in a work culture. CONCLUSION: The results of this
study show that healthcare personnel at a unit with a successful implementation
of change have a working environment with many positive qualities. This indicates
that a work environment with a high focus on goal achievement and task
orientation can handle the challenges of implementing changes.
PMID- 28705156
TI - Diet segregation in American bison (Bison bison) of Yellowstone National Park
(Wyoming, USA).
AB - BACKGROUND: Body size is a major factor in the nutritional ecology of ruminant
mammals. Females, due to their smaller size and smaller rumen, have more rapid
food-passage times than males and thereby require higher quality forage. Males
are more efficient at converting high-fiber forage into usable energy and thus,
are more concerned with quantity. American bison are sexually dimorphic and
sexually segregate for the majority of their adult lives, and in Yellowstone
National Park, they occur in two distinct subpopulations within the Northern and
Central ranges. We used fecal nitrogen and stable isotopes of carbon and nitrogen
from American bison to investigate sex-specific differences in diet composition,
diet quality, and dietary breadth between the mating season and a time period
spanning multiple years, and compared diet indicators for these different time
periods between the Northern and Central ranges. RESULTS: During mating season,
diet composition of male and female American bison differed significantly;
females had higher quality diets, and males had greater dietary breadth. Over the
multi-year period, females had higher quality diets and males, greater dietary
breadth. Diet segregation for bison in the Central Range was more pronounced
during the mating season than for the multi-year period and females had higher
quality diets than males. Finally, diet segregation in the Northern Range was
more pronounced during the multi-year period than during the mating season, and
males had greater dietary breadth. CONCLUSIONS: Female bison in Yellowstone
National Park have higher quality diets than males, whereas males ingest a
greater diversity of plants or plants parts, and bison from different ranges
exhibited more pronounced diet segregation during different times. Collectively,
our results suggest that diet segregation in bison of Yellowstone National Park
is associated with sex-specific differences in nutritional demands. Altogether,
our results highlight the importance of accounting for spatial and temporal
heterogeneity when conducting dietary studies on wild ungulates.
PMID- 28705157
TI - Ward social workers' views of what facilitates or hinders collaboration with
specialist palliative care team social workers: A grounded theory.
AB - BACKGROUND: Inpatient, generalist social workers in discharge planning roles work
alongside specialist palliative care social workers to care for patients, often
resulting in two social workers being concurrently involved in the same patient's
care. Previous studies identifying components of effective collaboration, which
impacts patient outcomes, care efficiency, professional job satisfaction, and
healthcare costs, were conducted with nurses and physicians but not social
workers. This study explores ward social workers' perceptions of what facilitates
or hinders collaboration with palliative care social workers. METHODS: Grounded
theory was used to explore the research aim. In-depth qualitative interviews with
masters trained ward social workers (n = 14) working in six hospitals located in
the Midwest, United States were conducted between February 2014 and January 2015.
A theoretical model of ward social workers' collaboration with palliative care
social workers was developed. RESULTS: The emerging model of collaboration
consists of: 1) trust, which is comprised of a) ability, b) benevolence, and c)
integrity, 2) information sharing, and 3) role negotiation. Effective
collaboration occurs when all elements of the model are present. CONCLUSION:
Collaboration is facilitated when ward social workers' perceptions of trust are
high, pertinent information is communicated in a time-sensitive manner, and a
flexible approach to roles is taken. The theoretical model of collaboration can
inform organisational policy and social work clinical practice guidelines, and
may be of use to other healthcare professionals, as improvements in collaboration
among healthcare providers may have a positive impact on patient outcomes.
PMID- 28705158
TI - "No patient should die of PPH just for the lack of training!" Experiences from
multi-professional simulation training on postpartum hemorrhage in northern
Tanzania: a qualitative study.
AB - BACKGROUND: Postpartum hemorrhage (PPH) is a major cause of maternal morbidity
and mortality. In Tanzania, PPH causes 25% of maternal deaths. Skilled attendance
is crucial to saving the lives of mothers and their newborns during childbirth.
This study is a follow-up after multi-professional simulation training on PPH in
northern Tanzania. The purpose was to enhance understanding and gain knowledge of
important learning features and outcomes related to multi-professional simulation
training on PPH. METHODS: The study had a descriptive and exploratory design.
After the second annual simulation training at two hospitals in northern
Tanzania, ten focus group discussions comprising 42 nurse midwives, doctors, and
medical attendants, were carried out. A semi-structured interview guide was used
during the discussions, which were audio-taped for qualitative content analysis
of manifest content. RESULTS: The most important findings from the focus group
discussions were the importance of team training as learning feature, and the
perception of improved ability to use a teamwork approach to PPH. Regardless of
profession and job tasks, the informants expressed enhanced self-efficacy and
reduced perception of stress. The informants perceived that improved competence
enabled them to provide efficient PPH management for improved maternal health.
They recommended simulation training to be continued and disseminated.
CONCLUSION: Learning features, such as training in teams, skills training, and
realistic repeated scenarios with consecutive debriefing for reflective learning,
including a systems approach to human error, were crucial for enhanced teamwork.
Informants' confidence levels increased, their stress levels decreased, and they
were confident that they offered better maternal services after training.
PMID- 28705159
TI - An att site-based recombination reporter system for genome engineering and
synthetic DNA assembly.
AB - BACKGROUND: Direct manipulation of the genome is a widespread technique for
genetic studies and synthetic biology applications. The tyrosine and serine site
specific recombination systems of bacteriophages HK022 and PhiC31 are widely used
for stable directional exchange and relocation of DNA sequences, making them
valuable tools in these contexts. We have developed site-specific recombination
tools that allow the direct selection of recombination events by embedding the
attB site from each system within the beta-lactamase resistance coding sequence
(bla). RESULTS: The HK and PhiC31 tools were developed by placing the attB sites
from each system into the signal peptide cleavage site coding sequence of bla.
All possible open reading frames (ORFs) were inserted and tested for
recombination efficiency and bla activity. Efficient recombination was observed
for all tested ORFs (3 for HK, 6 for PhiC31) as shown through a cointegrate
formation assay. The bla gene with the embedded attB site was functional for
eight of the nine constructs tested. CONCLUSIONS: The HK/PhiC31 att-bla system
offers a simple way to directly select recombination events, thus enhancing the
use of site-specific recombination systems for carrying out precise, large-scale
DNA manipulation, and adding useful tools to the genetics toolbox. We further
show the power and flexibility of bla to be used as a reporter for recombination.
PMID- 28705160
TI - Tracking development assistance and government health expenditures for 35 malaria
eliminating countries: 1990-2017.
AB - BACKGROUND: Donor financing for malaria has declined since 2010 and this trend is
projected to continue for the foreseeable future. These reductions have a
significant impact on lower burden countries actively pursuing elimination, which
are usually a lesser priority for donors. While domestic spending on malaria has
been growing, it varies substantially in speed and magnitude across countries. A
clear understanding of spending patterns and trends in donor and domestic
financing is needed to uncover critical investment gaps and opportunities.
METHODS: Building on the Institute for Health Metrics and Evaluation's annual
Financing Global Health research, data were collected from organizations that
channel development assistance for health to the 35 countries actively pursuing
malaria elimination. Where possible, development assistance for health (DAH) was
categorized by spend on malaria intervention. A diverse set of data points were
used to estimate government health budgets expenditure on malaria, including
World Malaria Reports and government reports when available. Projections were
done using regression analyses taking recipient country averages and earmarked
funding into account. RESULTS: Since 2010, DAH for malaria has been declining for
the 35 countries actively pursuing malaria elimination (from $176 million in 2010
to $62 million in 2013). The Global Fund is the largest external financier for
malaria, providing 96% of the total external funding for malaria in 2013, with
vector control interventions being the highest cost driver in all regions.
Government expenditure on malaria, while increasing, has not kept pace with
diminishing DAH or rising national GDP rates, leading to a potential gap in
service delivery needed to attain elimination. CONCLUSION: Despite past gains,
total financing available for malaria in elimination settings is declining.
Health financing trends suggest that substantive policy interventions will be
needed to ensure that malaria elimination is adequately financed and that
available financing is effectively targeted to interventions that provide the
best value for money.
PMID- 28705161
TI - Entrustment of the on-call senior medical resident role: implications for patient
safety and collective care.
AB - BACKGROUND: The on-call responsibilities of a senior medicine resident (SMR) may
include the admission transition of patient care on medical teaching teams (MTT),
supervision of junior trainees, and ensuring patient safety. In many
institutions, there is no standardised assessment of SMR competency prior to
granting these on-call responsibilities in internal medicine. In order to fulfill
competency based medical education requirements, training programs need to
develop assessment approaches to make and defend such entrustment decisions. The
purpose of this study is to understand the clinical activities and outcomes of
the on-call SMR role and provide training programs with a rigorous model for
entrustment decisions for this role. METHODS: This four phase study utilizes a
constructivist grounded theory approach to collect and analyse the following data
sets: case study, focus groups, literature synthesis of supervisory practices and
return-of-findings focus groups. The study was conducted in two Academic Health
Sciences Centres in Ontario, Canada. The case study included ten attending
physicians, 13 SMRs, 19 first year residents and 14 medical students. The focus
groups included 19 SMRs. The later, return-of-findings focus groups included ten
SMRs. RESULTS: Five core on-call supervisory tasks (overseeing ongoing patient
care, briefing, case review, documentation and preparing for handover) were
identified, as well as a range of practices associated with these tasks. We also
identified challenges that influenced the extent to which SMRs were able to
effectively perform the core tasks. At times, these challenges led to omissions
of the core tasks and potentially compromised patient safety and the admission
transition of care. CONCLUSION: By identifying the core supervisory tasks and
associated practices, we were able to identify the competencies for the on-call
SMR role. Our findings can further be used by training programs for assessment
and for making entrustment decisions.
PMID- 28705162
TI - The effect of autologous adipose derived mesenchymal stem cell therapy in the
treatment of a large osteochondral defect of the knee following unsuccessful
surgical intervention of osteochondritis dissecans - a case study.
AB - BACKGROUND: A prospective analysis of the effect of autologous adipose derived
mesenchymal stem cell (MSC) therapy in the treatment of an osteochondral defect
of the knee with early progressive osteoarthritis following unsuccessful surgical
intervention of osteochondritis dissecans (OCD). CASE PRESENTATION: After failed
conventional management of OCD a patient undergoes intra-articular MSC therapy.
Patient outcome measures included the Numeric Pain Rating Scale (NPRS), the
Western Ontario and McMaster Universities Arthritis Index (WOMAC) and the Knee
Injury and Osteoarthritis Outcome Score (KOOS). Structural outcome was assessed
using MRI with the novel technique of T2 mapping used to indicate cartilage
quality. Following MSC therapy the patient reported improvement in pain and
function as measured by NPRS, WOMAC and KOOS. Repeat MRI analysis showed
regeneration of cartilage. MRI T2 mapping indicated hyaline like cartilage
regrowth. CONCLUSION: In this report, the use of MSCs, after unsuccessful
conventional OCD management, resulted in structural, functional and pain
improvement. These results highlight the need to further study the regenerative
potential of MSC therapy. TRIAL REGISTRATION: Australian and New Zealand Clinical
Trial Registry Number - ACTRN12615000258550 (Date registered 19/03/2015 -
retrospectively registered).
PMID- 28705163
TI - A comprehensive intervention following the clinical pathway of eating and
swallowing disorder in the elderly with dementia: historically controlled study.
AB - BACKGROUND: Eating problems in patients with advanced dementia are strongly
associated with their deteriorating survival. Food and drink intake in people
with dementia may be supported by specific interventions, but the effectiveness
of such interventions is backed by almost no evidence. However, comprehensive
geriatric assessment (CGA) might potentially clarify the etiology of decreased
oral intake in people with dementia; thus improving their clinical outcomes.
METHODS: This study was a single-arm, non-randomized trial that included
historically controlled patients for comparison. We defined elderly patients with
both severely decreased oral intake depending on artificial hydration and/or
nutrition (AHN) and dementia as "Eating and Swallowing Disorder of the Elderly
with Dementia (ESDED)". In the intervention group, participants received CGA
through the original clinical pathway with multidisciplinary interventions. This
was followed by individualized therapeutic interventions according to assessment
of the etiology of their eating problems. RESULTS: During the intervention period
(between 1st April 2013 and 31st March 2015), 102 cases of ESDED were enrolled in
the study and 90 patients had completed receiving CGA. Conversely, 124 ESDED
patient controls were selected from the same hospital enrolled during the
historical period (between 1st April 2011 and 31st March 2012). Most participants
in both groups were bedridden with severe cognitive impairment. For the
intervention group, an average of 4.3 interventional strategies was recommended
per participant after CGA. Serological tests, diagnostic imaging and other
diagnostic examinations were much more frequently performed in the intervention
group. Recovery rate from ESDED in the intervention group was significantly
higher than that in the historical group (51% v.s. 34%, respectively, P = 0.02).
The 1-year AHN-free survival in the intervention group was significantly higher
than that in the historical group (28% v.s. 15%, respectively, P = 0.01). No
significant difference between the two groups was found for 1-year overall
survival (37% v.s. 28%, respectively, P = 0.08). CONCLUSIONS: Use of CGA with
multidisciplinary interventions could improve the functional status of eating and
allow elderly patients with severe eating problems and dementia to survive
independently without the need for AHN. TRIAL REGISTRATION: ISRCTN57646445 , this
trial was retrospectively registered on 8th December 2015.
PMID- 28705164
TI - Subscapularis- and deltoid-sparing vs traditional deltopectoral approach in
reverse shoulder arthroplasty: a prospective case-control study.
AB - BACKGROUND: With the growth of reverse shoulder arthroplasty (RSA), it is
becoming increasingly necessary to establish the most cost-effective methods for
the procedure. The surgical approach is one factor that may influence the cost
and outcome of RSA. The purpose of this study was to compare the clinical results
of a subscapularis- and deltoid-sparing (SSCS) approach to a traditional
deltopectoral (TDP) approach for RSA. The hypothesis was that the SSCS approach
would be associated with decreased length of stay (LOS), equal complication rate,
and better short-term outcomes compared to the TDP approach. METHODS: A
prospective evaluation was performed on patients undergoing RSA over a 2-year
period. A deltopectoral incision was used followed by either an SSCS approach or
a traditional tenotomy of the subscapularis (TDP). LOS, adverse events, physical
therapy utilization, and patient satisfaction were collected in the 12 months
following RSA. RESULTS: LOS was shorter with the SSCS approach compared to the
TDP approach (from 8.2 +/- 6.4 days to 15.2 +/- 11.9 days; P = 0.04). At 3 months
postoperative, the single assessment numeric evaluation score (80 +/- 11% vs 70
+/- 6%; P = 0.04) and active elevation (130 +/- 22 degrees vs 109 +/- 24 degrees
; P = 0.01) were higher in the SSCS group. The SSCS approach resulted in a net
cost savings of $5900 per patient. Postoperative physical therapy, pain levels,
and patient satisfaction were comparable in both groups. No immediate
intraoperative complications were noted. CONCLUSION: Using a SSCS approach is an
option for patients requiring RSA. Overall LOS is minimized compared to a TDP
approach with subscapularis tenotomy. The SSCS approach may provide substantial
healthcare cost savings, without increasing complication rate or decreasing
patient satisfaction.
PMID- 28705165
TI - On the plausibility of socioeconomic mortality estimates derived from linked
data: a demographic approach.
AB - BACKGROUND: Reliable estimates of mortality according to socioeconomic status
play a crucial role in informing the policy debate about social inequality,
social cohesion, and exclusion as well as about the reform of pension systems.
Linked mortality data have become a gold standard for monitoring socioeconomic
differentials in survival. Several approaches have been proposed to assess the
quality of the linkage, in order to avoid the misclassification of deaths
according to socioeconomic status. However, the plausibility of mortality
estimates has never been scrutinized from a demographic perspective, and the
potential problems with the quality of the data on the at-risk populations have
been overlooked. METHODS: Using indirect demographic estimation (i.e., the
synthetic extinct generation method), we analyze the plausibility of old-age
mortality estimates according to educational attainment in four European data
contexts with different quality issues: deterministic and probabilistic linkage
of deaths, as well as differences in the methodology of the collection of
educational data. We evaluate whether the at-risk population according to
educational attainment is misclassified and/or misestimated, correct these
biases, and estimate the education-specific linkage rates of deaths. RESULTS: The
results confirm a good linkage of death records within different educational
strata, even when probabilistic matching is used. The main biases in mortality
estimates concern the classification and estimation of the person-years of
exposure according to educational attainment. Changes in the census questions
about educational attainment led to inconsistent information over time, which
misclassified the at-risk population. Sample censuses also misestimated the at
risk populations according to educational attainment. CONCLUSION: The synthetic
extinct generation method can be recommended for quality assessments of linked
data because it is capable not only of quantifying linkage precision, but also of
tracking problems in the population data. Rather than focusing only on the
quality of the linkage, more attention should be directed towards the quality of
the self-reported socioeconomic status at censuses, as well as towards the
accurate estimation of the at-risk populations.
PMID- 28705166
TI - Looking back and moving forward: can we accelerate progress on adolescent
pregnancy in the Americas?
AB - Adolescent fertility rates in Latin America and the Caribbean (LAC) remain
unacceptably high, especially compared to the region's declining total fertility
rates. The Region has experienced the slowest progress of all regions in the
world, and shows major differences between countries and between subgroups in
countries. In 2013, LAC was also noted as the only region with a rising trend in
pregnancies in adolescents younger than 15 years. In response to the lack of
progress in the LAC region, PAHO/WHO, UNFPA and UNICEF held a technical
consultation with global, regional and country-level stakeholders to take stock
of the situation and agree on strategic approaches and priority actions to
accelerate progress. The meeting concluded that there is no single portrait of an
adolescent mother in LAC and that context and determinants of adolescent
pregnancy vary across and within countries. However, lack of knowledge about
their sexual and reproductive health and rights, poor access to and inadequate
use of contraceptives resulting from restrictive laws and policies, weak
programs, social and cultural norms, limited education and income, sexual
violence and abuse, and unequal gender relations were identified as key factors
contributing to adolescent pregnancy in LAC. The meeting participants highlighted
the following seven priority actions to accelerate progress: 1. Make adolescent
pregnancy, its drivers and impact, and the most affected groups more visible with
disaggregated data, qualitative reports, and stories. 2. Design interventions
targeting the most vulnerable groups, ensuring the approaches are adapted to
their realities and address their specific challenges. 3. Engage and empower
youth to contribute to the design, implementation and monitoring of strategic
interventions. 4. Abandon ineffective interventions and invest resources in
applying proven ones. 5. Strengthen inter-sectoral collaboration to effectively
address the drivers of adolescent pregnancy in LAC. 6. Move from boutique
projects to large-scale and sustainable programs. 7. Create an enabling
environment for gender equality and adolescent sexual and reproductive health and
rights.
PMID- 28705167
TI - Inhibition of Parkinsonian tremor with cutaneous afferent evoked by
transcutaneous electrical nerve stimulation.
AB - BACKGROUND: Recent study suggests that tremor signals are transmitted by way of
multi-synaptic corticospinal pathway. Neurophysiological studies have also
demonstrated that cutaneous afferents exert potent inhibition to descending motor
commands by way of spinal interneurons. We hypothesize in this study that
cutaneous afferents could also affect the transmission of tremor signals, thus,
inhibit tremor in patients with PD. METHODS: We tested this hypothesis by
activating cutaneous afferents in the dorsal hand skin innervated by superficial
radial nerve using transcutaneous electrical nerve stimulation (TENS). Eight
patients with PD having tremor dominant symptom were recruited to participate in
this study using a consistent experimental protocol for tremor inhibition.
Resting tremor and electromyogram (EMG) of muscles in the upper extremity of
these subjects with PD were recorded, while surface stimulation was applied to
the dorsal skin of the hand. Fifteen seconds of data were recorded for 5 s prior
to, during and post stimulation. Power spectrum densities (PSDs) of tremor and
EMG signals were computed for each data segment. The peak values of PSDs in three
data segments were compared to detect evidence of tremor inhibition. RESULTS: At
stimulation intensity from 1.5 to 1.75 times of radiating sensation threshold,
apparent suppressions of tremor at wrist, forearm and upper arm and in the EMGs
were observed immediately at the onset of stimulation. After termination of
stimulation, tremor and rhythmic EMG bursts reemerged gradually. Statistical
analysis of peak spectral amplitudes showed a significant difference in joint
tremors and EMGs during and prior to stimulation in all 8 subjects with PD. The
average percentage of suppression was 61.56% in tremor across all joints of all
subjects, and 47.97% in EMG of all muscles. The suppression appeared to occur
mainly in distal joints and muscles. There was a slight, but inconsistent effect
on tremor frequency in the 8 patients with PD tested. CONCLUSIONS: Our results
provide direct evidence that tremor in the upper extremity of patients with PD
can be inhibited to a large extent with evoked cutaneous reflexes via surface
stimulation of the dorsal hand skin area innervated by the superficial radial
nerve.
PMID- 28705168
TI - Relevance of breast MRI in determining the size and focality of invasive breast
cancer treated by mastectomy: a prospective study.
AB - BACKGROUND: The aim of this study was the evaluation of breast MRI in determining
the size and focality of invasive non-metastatic breast cancers. METHODS: The
prospective, single-centre study conducted in 2015 compared preoperative MRI with
histological analysis of mastectomy. RESULTS: One hundred one mastectomies from
98 patients were extensively analysed. The rates of false-positive and false
negative MRI were 2 and 4% respectively. The sensitivity of breast MRI was 84.7%
for the detection of all invasive foci, 69% for single foci and 65.7% for
multiple foci. In the evaluation of tumour size, the Spearman rank correlation
coefficient r between the sizes obtained by MRI and histology was 0.62. The MRI
based prediction of a complete response to neoadjuvant chemotherapy was 75%.
DISCUSSION: MRI exhibits high sensitivity in the detection of invasive breast
cancers. False positives were linked to the inflammatory nature of the tumour
bed. False negatives were associated with small or low-grade tumours and their
retro-areolar location. The size of T1 tumours was overestimated by an average of
7%, but MRI was the most efficient procedure. The sensitivity of MRI for the
diagnosis of unifocal tumours was higher than that for multifocal sites. Our
study confirmed the positive contribution of preoperative MRI for invasive
lobular carcinomas and complete response predictions after neoadjuvant
chemotherapy.
PMID- 28705169
TI - Antireflective nanocoatings for UV-sensation: the case of predatory owlfly
insects.
AB - Moth-eye nanostructures, discovered to coat corneae of certain nocturnal insects,
have inspired numerous technological applications to reduce light reflectance
from solar cells, light-emitting diodes, and optical detectors. Technological
developments require such nanocoatings to possess broadband antireflective
properties, transcending the visual light spectrum, in which animals typically
operate. Here we describe the corneal nanostructures of the visual organ
exclusive in UV sensation of the hunting insect Libelloides macaronius and report
their supreme anti-light-reflectance capacity.
PMID- 28705170
TI - Can Lokomat therapy with children and adolescents be improved? An adaptive
clinical pilot trial comparing Guidance force, Path control, and FreeD.
AB - BACKGROUND: Robot-assisted gait therapy is increasingly being used in pediatric
neurorehabilitation to complement conventional physical therapy. The robotic
device applied in this study, the Lokomat (Hocoma AG, Switzerland), uses a
position control mode (Guidance Force), where exact positions of the knee and hip
joints throughout the gait cycle are stipulated. Such a mode has two
disadvantages: Movement variability is restricted, and patients tend to walk
passively. Kinematic variability and active participation, however, are crucial
for motor learning. Recently, two new control modes were introduced. The Path
Control mode allows the patient to walk within a virtual tunnel surrounding the
ideal movement trajectory. The FreeD was developed to support weight shifting
through mediolaterally moveable pelvis and leg cuffs. The aims of this study were
twofold: 1) To present an overview of the currently available control modes of
the Lokomat. 2) To evaluate if an increase in kinematic variability as provided
by the new control modes influenced leg muscle activation patterns and intensity,
as well as heart rate while walking in the Lokomat. METHODS: In 15 adolescents
with neurological gait disorders who walked in the Lokomat, 3 conditions were
compared: Guidance Force, Path Control, and FreeD. We analyzed surface
electromyographic (sEMG) activity from 5 leg muscles of the more affected leg and
heart rate. Muscle activation patterns were compared with norm curves. RESULTS:
Several muscles, as well as heart rate, demonstrated tendencies towards a higher
activation during conditions with more kinematic freedom. sEMG activation
patterns of the M.rectus femoris and M.vastus medialis showed the highest
similarity to over-ground walking under Path Control, whereas walking under FreeD
led to unphysiological muscle activation in the tested sample. CONCLUSIONS:
Results indicate that especially Path Control seems promising for adolescent
patients undergoing neurorehabilitation, as it increases proximal leg muscle
activity while facilitating a physiological muscle activation. Therefore, this
may be a solution to increase kinematic variability and patients' active
participation in robot-assisted gait training.
PMID- 28705171
TI - Formula diet driven microbiota shifts tryptophan metabolism from serotonin to
tryptamine in neonatal porcine colon .
AB - BACKGROUND: The gut microbiota of breast-fed and formula-fed infants differ
significantly, as do the risks for allergies, gut dysfunction, and upper
respiratory tract infections. The connections between breast milk, various
formulas, and the profiles of gut bacteria to these childhood illnesses, as well
as the mechanisms underlying the effects, are not well understood. METHODS: We
investigated distal colon microbiota by 16S RNA amplicon sequencing, morphology
by histomorphometry, immune response by cytokine expression, and tryptophan
metabolism in a pig model in which piglets were sow-fed, or fed soy or dairy milk
based formula from postnatal day (PND) 2 to 21. RESULTS: Formula feeding
significantly (p < 0.05) altered the colon microbiota relative to the sow
feeding. A significant reduction in microbial diversity was noted with formula
groups in comparison to sow-fed. Streptococcus, Blautia, Citrobacter,
Butrycimonas, Parabacteroides, Lactococcus genera were increased with formula
feeding relative to sow feeding. In addition, relative to sow feeding,
Anaerotruncus, Akkermansia, Enterococcus, Acinetobacter, Christensenella, and
Holdemania were increased in milk-fed piglets, and Biliophila, Ruminococcus,
Clostridium were increased in soy-fed piglets. No significant gut morphological
changes were noted. However, higher cytokine mRNA expression (BMP4, CCL11, CCL21)
was observed in the distal colon of formula groups. Formula feeding reduced
enterochromaffin cell number and serotonin, but increased tryptamine levels
relative to sow feeding. CONCLUSION: Our data confirm that formula diet alters
the colon microbiota and appears to shift tryptophan metabolism from serotonin to
tryptamine, which may lead to greater histamine levels and risk of allergies in
infants.
PMID- 28705172
TI - Endocannabinoid receptor blockade reduces alanine aminotransferase in polycystic
ovary syndrome independent of weight loss.
AB - BACKGROUND: Evidence suggests that endocannabinoid system activation through the
cannabinoid receptor 1 (CB1) is associated with enhanced liver injury, and CB1
antagonism may be beneficial. The aim of this study was to determine the impact
of rimonabant (CB1 antagonist) on alanine aminotransferase (ALT), a
hepatocellular injury marker, and a hepatic inflammatory cytokine profile.
METHODS: Post hoc review of 2 studies involving 50 obese women with PCOS and well
matched for weight, randomised to weight reducing therapy; rimonabant (20 mg od)
or orlistat (120 mg tds), or to insulin sensitising therapy metformin, (500 mg
tds), or pioglitazone (45 mg od). No subject had non-alcoholic fatty liver
disease (NAFLD). RESULTS: Treatment with rimonabant for 12 weeks reduced both ALT
and weight (p < 0.01), and there was a negative correlation between Delta ALT and
Delta HOMA-IR (p < 0.001), but not between Delta ALT and Delta weight. There was
a significant reduction of weight with orlistat (p < 0.01); however, orlistat,
metformin and pioglitazone had no effect on ALT. The free androgen index fell in
all groups (p < 0.05). The inflammatory marker hs-CRP was reduced by pioglitazone
(p < 0.001) alone and did not correlate with changes in ALT. The inflammatory
cytokine profile for IL-1beta, IL-6, IL-7, IL-10, IL12, TNF-alpha, MCP-1 and INF
gamma did not differ between groups. None of the interventions had an effect on
biological variability of ALT. CONCLUSION: Rimonabant through CB1 receptor
blockade decreased serum ALT that was independent of weight loss and hepatic
inflammatory markers in obese women with PCOS without NAFLD. TRIAL REGISTRATION:
ISRCTN58369615 (February 2007; retrospectively registered) ISRCTN75758249
(October 2007; retrospectively registered).
PMID- 28705173
TI - Conserved sequences of BART and BHRF regions encoding viral microRNAs in Epstein
Barr virus-associated lymphoma.
AB - OBJECTIVE: Epstein-Barr virus (EBV) encodes at least 25 pri-microRNAs (miRNAs) in
two regions of its DNA genome, BART and BHRF. B95-8, an EBV reference strain, has
a deletion in the BART region. However, no information is available on the
deletions or mutations in the BART and BHRF regions in clinical samples of EBV
associated lymphoma. RESULTS: Nine DNA fragments encoding miR-BARTs and two
coding miR-BHRF1s were amplified by PCR from DNA samples extracted from 16 cases
of EBV-associated lymphoma. All the PCR products were sequenced directly. DNA
fragments encoding miR-BARTs and miR-BHRF1-1 were successfully amplified from all
samples. An adenine-to-guanine mutation in the DNA fragment encoding miR-BART2-3p
was detected in four of the 16 cases, and a cytosine-to-thymidine mutation in the
DNA fragment encoding miR-BART11-3p was detected in one of the 16 samples. These
mutations were not associated with any histological categories of lymphoma. In
conclusion, mutations were rarely observed in the DNA encoding viral miRNAs in
cases of lymphoma. This suggests that the DNA sequences of EBV-encoded miR-BARTs
and miR-BHRF1-1 are conserved in EBV-associated lymphoma.
PMID- 28705174
TI - Extensive colorectal lymphomatous polyposis complicated by acute intestinal
obstruction: a case report.
AB - BACKGROUND: Multiple lymphomatous polyposis is a rare type of gastrointestinal
lymphoma that extensively infiltrates the intestine. Multiple lymphomatous
polyposis originates from the mantle zone of the lymphoma follicle and is
considered to be a mantle cell lymphoma, which is a relatively aggressive type of
B-cell non-Hodgkin's lymphoma. We report an unusual case of a patient with
multiple lymphomatous polyposis with extensive colorectal involvement and acute
intestinal obstruction, an atypical complication of this rare disease. On the
basis of this case study, the pitfalls in gastrointestinal tract lymphomatous
polyposis diagnosis and prognosis, as well as the treatment options, are
discussed. CASE PRESENTATION: Our patient was a 76-year-old white woman with
asthenia, cramps, and swelling in the lower left quadrant of the abdomen, as well
as weight loss within the previous 5 months. A colonoscopy revealed polyps in the
rectum, sigmoid colon, descending colon, and right and left colic flexures. A
biopsy revealed lymphomatous infiltration of the intestinal wall. Because of the
large size of the polypoid masses, which narrowed the colonic lumen in multiple
locations, the patient developed acute intestinal obstruction and was referred
for laparotomy. She underwent a total proctocolectomy with a permanent ileostomy
and a left salpingo-oophorectomy. Microscopic examination showed the presence of
a multicentric, low-grade, small lymphocytic lymphoma. Immunohistochemical
analysis revealed positive immunostaining for CD79a, CD20, and CD45. These
results were consistent with the diagnosis of mantle cell lymphoma. Two weeks
after surgery and prior to discharge, but before the beginning of chemotherapy,
the patient's general condition worsened as she experienced a severe and
progressive respiratory tract infection, advanced respiratory insufficiency, and
septic shock, and she ultimately died. CONCLUSIONS: Mantle cell lymphoma develops
as a progressive and aggressive disease with widespread polyposis of the
gastrointestinal tract. The intensive chemotherapeutic regimens usually result in
the regression of macroscopic and microscopic lesions; however, remissions are
short in duration, and the median length of patient survival is 3-4 years. Mantle
cell lymphoma is a rare disease that should be part of the differential diagnosis
of polypoid diseases of the large intestine.
PMID- 28705175
TI - Serotype-specific role of antigen I/II in the initial steps of the pathogenesis
of the infection caused by Streptococcus suis.
AB - Streptococcus suis is one of the most important post-weaning porcine bacterial
pathogens worldwide. The serotypes 2 and 9 are often considered the most virulent
and prevalent serotypes involved in swine infections, especially in Europe.
However, knowledge of the bacterial factors involved in the first steps of the
pathogenesis of the infection remains scarce. In several pathogenic streptococci,
expression of multimodal adhesion proteins known as antigen I/II (AgI/II) have
been linked with persistence in the upper respiratory tract and the oral cavity,
as well as with bacterial dissemination. Herein, we report expression of these
immunostimulatory factors by S. suis serotype 2 and 9 strains and that AgI/II
encoding genes are carried by integrative and conjugative elements. Using
mutagenesis and different in vitro assays, we demonstrate that the contribution
of AgI/II to the virulence of the serotype 2 strain used herein appears to be
modest. In contrast, data demonstrate that the serotype 9 AgI/II participates in
self-aggregation, induces salivary glycoprotein 340-related aggregation,
contributes to biofilm formation and increased strain resistance to low pH, as
well as in bacterial adhesion to extracellular matrix proteins and epithelial
cells. Moreover, the use of a porcine infection model revealed that AgI/II
contributes to colonization of the upper respiratory tract of pigs. Taken
together, these findings suggest that surface exposed AgI/II likely play a key
role in the first steps of the pathogenesis of the S. suis serotype 9 infection.
PMID- 28705176
TI - Time to immunologic recovery and determinant factors among adults who initiated
ART in Felege Hiwot Referral Hospital, northwest Ethiopia.
AB - BACKGROUND: CD4 cells are the major targets for human immunodeficiency virus
(HIV) and treatment with Antiretroviral Therapy (ART) influences the CD4 cell
count of HIV patients. In addition to ART, the time required to reach normal
range of CD4 counts (500 cells/mm3) can be affected by clinical, socio
demographic, and behavioral factors. This retrospective cohort study was
conducted to determine the incidence of having the normal range of CD4 cell
counts and factors that affect the time required to reach this normal range among
adult HIV patients who initiated into ART. METHODS: Data of 4 years were
retrospectively retrieved from routinely registered characteristics of 937 ART
users enrolled in 2010. Survival time until immunologic recovery and its
determinant factors were examined using the frailty model with different
parametric distributions alternatively. RESULTS: Most (80.8%) of the ART
attendants had CD4 cell count of 200 cells/mm3 or less at initiation. The overall
incidence rate of immunologic recovery was 12.67 persons per 1000 person-months
(95% CI 11.30, 14.20). The dependency of frailties of immunologic recovery by
residence was statistically significant (Theta = 0.05, p value = 0.006). Baseline
age (Adjusted Hazard Ratio (AHR) = 0.98, 95% CI 0.97, 0.99), baseline CD4 count
(AHR = 1.006, 95% CI 1.005, 1.008), and female sex (AHR = 1.34, 95% CI 1.03,
1.73) were significantly associated with shorter survival time for immunologic
recovery. CONCLUSION: Higher baseline CD4 count, lower baseline age, and female
sex were positively associated with the time to immunologic recovery, which also
dependent on proximity/residence of ART users. Therefore, further scale up of ART
services with due emphasis to patients with low CD4 count at baseline
particularly for male and older ART users are recommended to reach the normal
range of CD4 count in a shorter time of treatment.
PMID- 28705177
TI - Patterns and predictors of analgesic use in pregnancy: a longitudinal drug
utilization study with special focus on women with migraine.
AB - BACKGROUND: Few studies have investigated the drug utilization patterns and
factors predicting drug use in pregnant women with migraine. This longitudinal
drug utilization study aimed to describe patterns of analgesic use in a sample of
Norwegian pregnant women according to their migraine history, and to identify
predictors for analgesic use among these women. METHODS: Pregnant women giving
birth at Akershus University Hospital between 2008 and 2010 were recruited at
ultrasound examination in gestational week 17. Data were collected by
questionnaires in gestational weeks 17 and 32, and at 8 weeks postpartum, and
linked to birth records. Women were grouped into four categories according to
migraine history: no migraine history, previous migraine history, recent migraine
history (within 1 year prior to pregnancy) and migraine in pregnancy. Patterns of
use of analgesics were analyzed descriptively. Multivariable logistic regression
was used to identify factors predicting analgesic use. RESULTS: Out of 1981
women, 5.0% reported having migraine in pregnancy, 13.2% had a recent history of
migraine, 11.5% had a previous history of migraine, and 68.8% reported no history
of migraine. Analgesic use declined during pregnancy. Many women switched from
triptans and non-steroidal anti-inflammatory drugs to paracetamol, which
constituted most of the analgesic use. Factors associated with analgesic use
included recent migraine history (OR 1.6, 95% CI 1.2-2.2), more severe headache
intensity (OR 1.3, 95% CI 1.3-1.4), smoking (OR 1.9, 95% CI 1.1-3.3) and
multiparity (OR 1.4, 95% CI 1.1-1.7). CONCLUSIONS: Women with migraine stop or
switch medications during pregnancy. Analgesic use in pregnancy is affected by
migraine characteristics and intensity, and also by socio-demographic factors.
Clinicians should bear this in mind when giving advice on adequate management of
migraine in pregnancy and safe analgesic use.
PMID- 28705178
TI - Hepatitis a virus genotypes and strains from an endemic area of Europe, Bulgaria
2012-2014.
AB - BACKGROUND: Hepatitis A virus (HAV) infection is endemic in Eastern European and
Balkan region countries. In 2012, Bulgaria showed the highest rate (67.13 cases
per 100,000) in Europe. Nevertheless, HAV genotypes and strains circulating in
this country have never been described. The present study reports the molecular
characterization of HAV from 105 patients from Bulgaria. METHODS: Anti-HAV IgM
positive serum samples collected in 2012-2014 from different towns and villages
in Bulgaria were analysed by nested RT-PCR, sequencing of the VP1/2A region and
phylogenetic analysis; the results were analysed together with patient and
geographical data. RESULTS: Phylogenetic analysis revealed two main sequence
groups corresponding to the IA (78/105, 74%) and IB (27/105, 26%) sub-genotypes.
In the IA group, a major and a minor cluster were observed (62 and 16 sequences,
respectively). Most sequences from the major cluster (44/62, 71%) belonged to
either of two strains, termed "strain 1" and "strain 2", differing only for a
single specific nucleotide; the remaining sequences (18/62, 29%) showed few (1 to
4) nucleotide variations respect to strain 1 and 2. Strain 2 is identical to the
strain previously responsible for an outbreak in the Czech Republic in 2008 and a
large multi-country European outbreak caused by contaminated mixed frozen berries
in 2013. Most sequences of the IA minor cluster and the IB group were detected in
large/medium centers (LMCs). Overall, sequences from the IA major cluster were
more frequent in small centers (SCs), but strain 1 and strain 2 showed an
opposite relative frequency in SCs and LMCs (strain 1 more frequent in SCs,
strain 2 in LMCs). CONCLUSIONS: Genotype IA predominated in Bulgaria in 2012-2014
and phylogenetic analysis identified a major cluster of highly related or
identical IA sequences, representing 59% of the analysed cases; these isolates
were mostly detected in SCs, in which HAV shows higher endemicity than in LMCs.
The distribution of viral sequences suggests the existence of some differences
between the transmission routes in SCs and LMCs. Molecular characterization of an
increased number of isolates from Bulgaria, regularly collected over time, will
be useful to explore specific transmission routes and plan appropriate preventing
measures.
PMID- 28705179
TI - Improving health literacy through group antenatal care: a prospective cohort
study.
AB - BACKGROUND: To examine whether exposure to group antenatal care increased women's
health literacy by improving their ability to interpret and utilize health
messages compared to women who received standard, individual antenatal care in
Ghana. METHODS: We used a prospective cohort design. The setting was a busy urban
district hospital in Kumasi, the second most populous city in Ghana. Pregnant
women (N = 240) presenting for their first antenatal visit between 11 and 14
weeks gestation were offered participation in the study. A 27% drop-out rate was
experienced due to miscarriage, transfer or failure to return for follow-up
visits, leaving 184 women in the final sample. Data were collected using an
individual structured survey and medical record review. Summary statistics as
well as two sample t-tests or chi-square were performed to evaluate the group
effect. RESULTS: Significant group differences were found. Women participating in
group care demonstrated improved health literacy by exhibiting a greater
understanding of how to operationalize health education messages. There was a
significant difference between women enrolled in group antenatal care verses
individual antenatal care for preventing problems before delivery, understanding
when to access care, birth preparedness and complication readiness, intent to use
a modern method of family planning postpartum, greater understanding of the
components of breastfeeding and lactational amenorrhea for birth spacing, and
intent for postpartum follow-up. CONCLUSION: Group antenatal care as compared to
individual care offers an opportunity to increase quality of care and improve
maternal and newborn outcomes. Group antenatal care holds the potential to
increase healthy behaviors, promote respectful maternity care, and generate
demand for services. Group ANC improves women's health literacy on how to prevent
and recognize problems, prepare for delivery, and care for their newborn.
PMID- 28705180
TI - Etiology and prognosis of acute viral encephalitis and meningitis in Chinese
children: a multicentre prospective study.
AB - BACKGROUND: In China, there were few studies about the pathogens of acute viral
encephalitis and meningitis in children in recent years. The aims of this study
were to characterize the etiology and prognosis of acute viral encephalitis and
meningitis in Chinese children. METHODS: This was a multicentre prospective
study. Two hundred and sixty one viral encephalitis patients and 285 viral
meningitis patients were enrolled. The mean age of viral encephalitis and
meningitis were 5.88 +/- 3.60 years and 6.39 +/- 3.57 years, respectively. Real
time reverse transcription PCR and multiplex PCR were used to detect human
enteroviruses and herpes viruses in cerebrospinal fluid (CSF) of patients with
encephalitis or meningitis. The enzyme-linked immune absorbent assay (ELISA) was
used for detecting IgM antibody against Japanese encephalitis virus (JEV) in CSF
and against mumps virus, tick-borne encephalitis virus (TBEV), dengue virus and
rubella virus in acute serum. The clinical and outcome data were collected during
patients' hospitalization. RESULTS: The etiology of viral encephalitis was
confirmed in 52.5% patients. The primary pathogen was human enteroviruses (27.7%)
in viral encephalitis. The incidence of sequelae and the fatality rate of viral
encephalitis with confirmed etiology were 7.5% and 0.8%, respectively. The
etiology of viral meningitis was identified in 42.8% cases. The leading pathogen
was also human enteroviruses (37.7%) in viral meningitis. The prognosis of viral
meningitis was favorable with only 0.7% patients had neurological sequelae.
CONCLUSIONS: Human enteroviruses were the leading cause both in acute viral
encephalitis and viral meningitis in children. The incidence of sequelae and
fatality rate of viral encephalitis with confirmed etiology were 7.5% and 0.8%,
respectively. The prognosis of viral meningitis was favorable compared to viral
encephalitis.
PMID- 28705181
TI - The impact of antiretroviral therapy on symptom burden among HIV outpatients with
low CD4 count in rural Uganda: nested longitudinal cohort study.
AB - BACKGROUND: Individuals with HIV have a high prevalence of physical and
psychological symptoms throughout their disease course. Despite the clinical and
public health implications of unresolved pain and symptoms, little is known about
the effect of anti-retroviral therapy (ART) on these outcomes. This study aimed
to assess the impact on symptom burden for the year after ART initiation in
individuals with a CD4 count <200 cells/uL in Uganda. METHODS: HIV-infected, ART
naive adults referred from voluntary testing and counseling services in rural
Uganda for enrollment into a randomized controlled trial to test fluconazole as
primary prophylaxis against cryptococcal disease were invited to complete the
Memorial Symptom Assessment Scale-Short Form (MSAS-SF) prior to commencing ART
and at two subsequent follow up visits. This tool measures self-reported 7-day
period prevalence and associated burden of physical and psychological symptoms.
Changes in the total number of symptoms and distress indices with time on ART and
trial arm were investigated through fitting Linear Mixed Models for repeated
measures. RESULTS: During the first year of ART initiation the prevalence of most
individual symptoms remained constant. The notable exceptions which improved
after commencing ART are as follow; prevalence of pain (prevalence changed from
79% to 60%), weight loss (67% to 31%), lack of appetite (46% to 28%), feeling sad
(52% to 25%) and difficulty sleeping (35% to 23%). The total number of symptoms
and distress indices reduced after treatment commenced. Of concern was that half
or more study participants remained with symptoms of pain (60%), itching (57%),
skin changes (53%) and numbness in hands and feet (52%) after starting ART.
Sixteen symptoms remained with a burden of 25% or more. CONCLUSION: Despite the
beneficial effect of ART on reducing symptoms, some patients continue to
experience a high symptom burden. It is essential that HIV services in sub
Saharan Africa integrate management of symptoms into their programmes. TRIAL
REGISTRATION: CRYPTOPRO [ISRCTN 76481529 ], November 2004.
PMID- 28705182
TI - Chemoradiation in elderly esophageal cancer patients: rationale and design of a
phase I/II multicenter study (OSAGE).
AB - BACKGROUND: The management of elderly patients with cancer is a therapeutic
challenge and a public health problem. Definitive chemoradiotherapy (CRT) is an
accepted standard treatment for patients with locally advanced esophageal cancer
who cannot undergo surgery. However, there are few reports regarding tolerance to
CRT in elderly patients. We previously reported results for CRT in patients aged
>=75 years. Following this first phase II trial, we propose to conduct a phase
I/II study to evaluate the combination of carboplatin and paclitaxel, with
concurrent RT in unresectable esophageal cancer patients aged 75 years or older.
METHODS/DESIGN: This prospective multicenter phase I/II study will include
esophageal cancer in patients aged 75 years or older. Study procedures will
consist to determinate the tolerated dose of chemotherapy (Carboplatin,
paclitaxel) and of radiotherapy (41.4-45 and 50.4 Gy) in the phase I. Efficacy
will be assessed using a co-primary endpoint encompassing health related quality
of life and the progression-free survival in the phase II with the dose
recommended of CRT in the phase I. This geriatric evaluation was defined by the
French geriatric oncology group (GERICO). DISCUSSION: This trial has been
designed to assess the tolerated dose of CRT in selected patient aged 75 years or
older. TRIAL REGISTRATION: Clinicaltrials.gov ID: NCT02735057 . Registered on 18
March 2016.
PMID- 28705183
TI - Generic amplification and next generation sequencing reveal Crimean-Congo
hemorrhagic fever virus AP92-like strain and distinct tick phleboviruses in
Anatolia, Turkey.
AB - BACKGROUND: Ticks are involved with the transmission of several viruses with
significant health impact. As incidences of tick-borne viral infections are
rising, several novel and divergent tick- associated viruses have recently been
documented to exist and circulate worldwide. This study was performed as a cross
sectional screening for all major tick-borne viruses in several regions in
Turkey. Next generation sequencing (NGS) was employed for virus genome
characterization. Ticks were collected at 43 locations in 14 provinces across the
Aegean, Thrace, Mediterranean, Black Sea, central, southern and eastern regions
of Anatolia during 2014-2016. Following morphological identification, ticks were
pooled and analysed via generic nucleic acid amplification of the viruses
belonging to the genera Flavivirus, Nairovirus and Phlebovirus of the families
Flaviviridae and Bunyaviridae, followed by sequencing and NGS in selected
specimens. RESULTS: A total of 814 specimens, comprising 13 tick species, were
collected and evaluated in 187 pools. Nairovirus and phlebovirus assays were
positive in 6 (3.2%) and 48 (25.6%) pools. All nairovirus sequences were closely
related to the Crimean-Congo hemorrhagic fever virus (CCHFV) strain AP92 and
formed a phylogenetically distinct cluster among related strains. Major portions
of the CCHFV genomic segments were obtained via NGS. Phlebovirus sequencing
revealed several tick-associated virus clades, including previously-characterized
Antigone, Lesvos, KarMa and Bole tick viruses, as well as a novel clade. A wider
host range for tick-associated virus strains has been observed. NGS provided near
complete sequences of the L genomic segments of Antigone and KarMa clades, as
well as Antigone partial S segment. Co- infections of CCHFV and KarMa or novel
phlebovirus clades were detected in 2.1% of the specimens. CONCLUSIONS:
Widespread circulation of various tick-associated phlebovirus clades were
documented for the first time in Anatolia. Genomes of CCHFV AP92 strains were
identified in previously unexplored locations. NGS provided the most detailed
genomic characterization of the Antigone and KarMa viruses to date. The
epidemiological and health-related consequences must be elucidated.
PMID- 28705184
TI - Prevalence of gestational diabetes mellitus based on various screening strategies
in western Kenya: a prospective comparison of point of care diagnostic methods.
AB - BACKGROUND: Early diagnosis of gestational diabetes mellitus (GDM) is crucial to
prevent short term delivery risks and long term effects such as cardiovascular
and metabolic diseases in the mother and infant. Diagnosing GDM in Sub-Saharan
Africa (SSA) however, remains sub-optimal due to associated logistical and cost
barriers for resource-constrained populations. A cost-effective strategy to
screen for GDM in such settings are therefore urgently required. We conducted
this study to determine the prevalence of gestational diabetes mellitus (GDM) and
assess utility of various GDM point of care (POC) screening strategies in a
resource-constrained setting. METHODS: Eligible women aged >=18 years, and
between 24 and 32 weeks of a singleton pregnancy, prospectively underwent testing
over two days. On day 1, a POC 1-h 50 g glucose challenge test (GCT) and a POC
glycated hemoglobin (HbA1c) was assessed. On day 2, fasting blood glucose, 1-h
and 2-h 75 g oral glucose tolerance test (OGTT) were determined using both venous
and POC tests, along with a venous HbA1c. The International Association of
Diabetes in Pregnancy Study Group (IADPSG) criteria was used to diagnose GDM. GDM
prevalence was reported with 95% confidence interval (CI). Specificity,
sensitivity, positive predictive value, and negative predictive value of the
various POC testing strategies were determined using IADPSG testing as the
standard reference. RESULTS: Six hundred-sixteen eligible women completed testing
procedures. GDM was diagnosed in 18 women, a prevalence of 2.9% (95% CI, 1.57% -
4.23%). Compared to IADPSG testing, POC IADPSG had a sensitivity and specificity
of 55.6% and 90.6% respectively while that of POC 1-h 50 g GCT (using a
diagnostic cut-off of >=7.2 mmol/L [129.6 mg/dL]) was 55.6% and 63.9%. All other
POC tests assessed showed poor sensitivity. CONCLUSIONS: POC screening strategies
though feasible, showed poor sensitivity for GDM detection in our resource
constrained population of low GDM prevalence. Studies to identify sensitive and
specific POC GDM screening strategies using adverse pregnancy outcomes as end
points are required. TRIALS REGISTRATION: Clinical trials.gov : NCT02978807 ,
Registered 29 November 2016.
PMID- 28705185
TI - "You've got a friend in me": can social networks mediate the relationship between
mood and MCI?
AB - BACKGROUND: Social networks can change with age, for reasons that are adaptive or
unwanted. Social engagement is beneficial to both mental health and cognition,
and represents a potentially modifiable factor. Consequently this study explored
this association and assessed whether the relationship between mild cognitive
impairment (MCI) and mood problems was mediated by social networks. METHODS: This
study includes an analysis of data from the Cognitive Function and Ageing Study
Wales (CFAS Wales). CFAS Wales Phase 1 data were collected from 2010 to 2013 by
conducting structured interviews with older people aged over 65 years of age
living in urban and rural areas of Wales, and included questions that assessed
cognitive functioning, mood, and social networks. Regression analyses were used
to investigate the associations between individual variables and the mediating
role of social networks. RESULTS: Having richer social networks was beneficial to
both mood and cognition. Participants in the MCI category had weaker social
networks than participants without cognitive impairment, whereas stronger social
networks were associated with a decrease in the odds of experiencing mood
problems, suggesting that they may offer a protective effect against anxiety and
depression. Regression analyses revealed that social networks are a significant
mediator of the relationship between MCI and mood problems. CONCLUSIONS: These
findings are important, as mood problems are a risk factor for progression from
MCI to dementia, so interventions that increase and strengthen social networks
may have beneficial effects on slowing the progression of cognitive decline.
PMID- 28705186
TI - Objectively measured physical environmental neighbourhood factors are not
associated with accelerometer-determined total sedentary time in adults.
AB - BACKGROUND: The physical neighbourhood environment may influence adults'
sedentary behaviour. Yet, most studies examining the association between the
physical neighbourhood environment and sedentary behaviour rely on self-reported
data of either the physical neighbourhood environment and/or sedentary behaviour.
The aim of this study was to investigate the associations between objectively
measured physical environmental neighbourhood factors and accelerometer
determined total sedentary time in adults. METHODS: In total, 219 Dutch and 128
Belgian adults (mean age +/- SD: 55.8 +/- 15.4 years) were recruited between
March and August 2014 as part of the European SPOTLIGHT project. Physical
environmental neighbourhood factors, grouped into eight domains, i.e. walking,
cycling, public transport, aesthetics, land use mix, grocery stores, food outlets
and recreational facilities, were assessed using the SPOTLIGHT Virtual Audit
Tool. Sedentary time was collected using ActiGraph GT3X+ accelerometers. General
linear mixed models were conducted to examine associations between physical
environmental neighbourhood factors and total sedentary time. RESULTS:
Participants were sedentary, on average, for 542.9 min/day (SD: 84.3), or 9.1
h/day. None of the examined physical environmental neighbourhood factors were
significantly related to total sedentary time. CONCLUSIONS: Our findings do not
support associations of objectively measured physical environmental neighbourhood
factors with adults' objectively sedentary time in Dutch and Belgian adults. More
research on sedentary behaviours in settings such as the home and work setting is
needed to examine the influence of more specific physical environmental factors
on these context-specific sedentary behaviours.
PMID- 28705187
TI - Analysis of home-based rehabilitation in patients with motor impairment in
primary care: a prospective observational study.
AB - BACKGROUND: The purpose of health and social policies is to encourage older
people more longevity, remain free of disability and experience quality of life
while living in their homes. The aim of this study was to describe the
characteristics of 473 patients diagnosed with motor impairment in primary care,
the objectives of home-based rehabilitation and its functional impact. METHODS:
This prospective observational study was conducted in the Almeria Health
District. The analysed variables included age, gender, secondary diagnosis,
Barthel Index (BI), physiotherapeutic objectives and techniques, and number of
sessions. RESULTS: The sample had a mean age of 83 years, and 59% were women. The
assessed conditions with a high prevalence included osteoarticular pathology
(55%), Alzheimer's disease (15.1%), cardiovascular disease (13.7%) and stroke
(6.5%). The techniques applied mainly consisted of functional exercises (57.1%),
caregiver education (13.8%), and technical assistance (5.7%). There were
statistically significant differences (t = -15.79; p < 0.001) between initial (X
= 34.8) and final BI (X = 48.1), with an improvement of 13.4 points in patients'
functional capacity (95% confidence interval [CI]: -15.0 to -11.7). An equation
was constructed to predict patients' final BI as a function of the initial BI
using a multiple linear regression model. The regression model explained 78% of
the variance in patients with motor impairment. CONCLUSIONS: Important
improvements were obtained in terms of functional capacity with a mean of ten
sessions of physiotherapy. Lower patient age was correlated with higher initial
and final functional capacities in primary care. This study aimed to present a
useful starting point for decision making among management and health
administration regarding this population group by approaching the process from
the reality of practice and in relation to the rehabilitation provided. TRIAL
REGISTRATION: ClinicalTrials.gov identifier: NCT02715245 ; Date of registration:
18 January 2016.
PMID- 28705188
TI - Home delivery among antenatal care booked women in their last pregnancy and
associated factors: community-based cross sectional study in Debremarkos town,
North West Ethiopia, January 2016.
AB - BACKGROUND: In Ethiopia, nearly half of the mothers who were booked for antenatal
care, who supposed to have institutional delivery, gave home delivery nationally.
Home delivery accounts majority while few of childbirth were attended by the
skilled provider in Amhara regional state. This study aimed to determine the
proportion of home delivery and associated factors among antenatal care booked
women who gave childbirth in the past 1 year in Debremarkos Town, Northwest
Ethiopia. METHODS: A community-based Cross sectional study was conducted from
January 1st- 25th 2016. Epi Info version 7 was used to determine a total sample
size of 518 and simple random sampling procedure was employed. Data was collected
through an interview by using pretested structured questionnaire. Data were
entered into Epi Info version 7, cleaned and exported to SPSS version 21 for
analysis. A p-value less than or equals to 0.05 at 95% Confidence Intervals of
odds ratio were taken as significance level in the multivariable model. RESULTS:
A total of 127 (25.3%) women gave childbirth at home. Un-attending formal
education (Adjusted Odds Ratio = 7.56, 95% CI: [3.28, 17.44]), absence of health
facility within 30 min distance (AOR = 3.41, 95% CI: [1.42, 8.20]), not exposed
to media (AOR = 4.46, 95% CI: [2.09, 9.49]), Unplanned pregnancy (AOR = 3.47, 95%
CI [1.82, 6.61]), attending ANC at health post (AOR = 5.45, 95% CI: (1.21, 24.49)
and health center (AOR = 2.74, 95% CI [1.29, 5.82]), perceived privacy during ANC
(AOR = 3.69[1.25, 10.91]) and less than four times ANC visit (AOR = 5.04, 95% CI
(2.30, 11.04]) were significantly associated with home delivery. CONCLUSIONS:
Home delivery in this study was found to be low. Educational level, media
exposure, geographic access to a health facility, Unplanned pregnancy, an
institution where ANC was booked, perceived privacy during ANC and number of ANC
visit were found to be determinants of home delivery. Health institutions, health
professionals, policy makers, community leaders and all concerned with the
planning and implementation of maternity care in Ethiopia need to consider these
associations in implementing services and providing care, for pregnant women.
PMID- 28705189
TI - A biomechanical comparison of conventional dynamic compression plates and string
of-pearlsTM locking plates using cantilever bending in a canine Ilial fracture
model.
AB - BACKGROUND: Fracture of the ilium is common orthopedic injury that often requires
surgical stabilization in canine patients. Of the various methods of surgical
stabilization available, application of a lateral bone plate to the ilium is the
most common method of fixation. Many plating options are available, each having
its own advantages and disadvantages. The purpose of this study was to evaluate
the biomechanical properties of a 3.5 mm String-of-PearlsTM plate and a 3.5 mm
dynamic compression plate in a cadaveric canine ilial fracture model. Hemipelves
were tested in cantilever bending to failure and construct stiffness, yield load,
displacement at yield, ultimate load, and mode of failure were compared. RESULTS:
The mean stiffness of dynamic compression plate (116 +/- 47 N/mm) and String-of
PearlsTM plate (107 +/- 18 N/mm) constructs, mean yield load of dynamic
compression plate (793 +/- 333 N) and String-of-PearlsTM plate (860 +/- 207 N)
constructs, mean displacement at yield of dynamic compression plate (8.6 +/- 3.0
mm) and String-of-PearlsTM plate (10.2 +/- 2.8 mm) constructs, and ultimate load
at failure of dynamic compression plate (936 +/- 320 N) and String-of-PearlsTM
plate (939 +/- 191 N) constructs were not significantly different. No differences
were found between constructs with respect to mode of failure. CONCLUSIONS: No
significant biomechanical differences were found between String-of-PearlsTM plate
and dynamic compression plate constructs in this simplified cadaveric canine
ilial fracture model.
PMID- 28705190
TI - Low dose aspirin in the prevention of recurrent spontaneous preterm labour - the
APRIL study: a multicenter randomized placebo controlled trial.
AB - BACKGROUND: Preterm birth (birth before 37 weeks of gestation) is a major problem
in obstetrics and affects an estimated 15 million pregnancies worldwide annually.
A history of previous preterm birth is the strongest risk factor for preterm
birth, and recurrent spontaneous preterm birth affects more than 2.5 million
pregnancies each year. A recent meta-analysis showed possible benefits of the use
of low dose aspirin in the prevention of recurrent spontaneous preterm birth. We
will assess the (cost-)effectiveness of low dose aspirin in comparison with
placebo in the prevention of recurrent spontaneous preterm birth in a randomized
clinical trial. METHODS/DESIGN: Women with a singleton pregnancy and a history of
spontaneous preterm birth in a singleton pregnancy (22-37 weeks of gestation)
will be asked to participate in a multicenter, randomized, double blinded,
placebo controlled trial. Women will be randomized to low dose aspirin (80 mg
once daily) or placebo, initiated from 8 to 16 weeks up to maximal 36 weeks of
gestation. The primary outcome measure will be preterm birth, defined as birth at
a gestational age (GA) < 37 weeks. Secondary outcomes will be a composite of
adverse neonatal outcome and maternal outcomes, including subgroups of
prematurity, as well as intrauterine growth restriction (IUGR) and costs from a
healthcare perspective. Preterm birth will be analyzed as a group, as well as
separately for spontaneous or indicated onset. Analysis will be performed by
intention to treat. In total, 406 pregnant women have to be randomized to show a
reduction of 35% in preterm birth from 36 to 23%. If aspirin is effective in
preventing preterm birth, we expect that there will be cost savings, because of
the low costs of aspirin. To evaluate this, a cost-effectiveness analysis will be
performed comparing preventive treatment with aspirin with placebo. DISCUSSION:
This trial will provide evidence as to whether or not low dose aspirin is (cost-)
effective in reducing recurrence of spontaneous preterm birth. TRIAL
REGISTRATION: Clinical trial registration number of the Dutch Trial Register: NTR
5675 . EudraCT-registration number: 2015-003220-31.
PMID- 28705191
TI - Knowledge and understanding of health insurance: challenges and remedies.
AB - As coverage is expanded in health systems that rely on consumers to choose health
insurance plans that best meet their needs, interest in whether consumers possess
sufficient understanding of health insurance to make good coverage decisions is
growing. The recent IJHPR article by Green and colleagues-examining understanding
of supplementary health insurance (SHI) among Israeli consumers-provides an
important and timely answer to the above question. Indeed, their study addresses
similar problems to the ones identified in the US health care market, with two
notable findings. First, they show that overall-regardless of demographic
variables-there are low levels of knowledge about SHI, which the literature has
come to refer to more broadly as "health insurance literacy." Second, they find a
significant disparity in health insurance literacy between different SES groups,
where Jews were significantly more knowledgeable about SHI compared to their Arab
counterparts.The authors' findings are consistent with a growing body of
literature from the U.S. and elsewhere, including our own, presenting evidence
that consumers struggle with understanding and using health insurance. Studies in
the U.S. have also found that difficulties are generally more acute for
populations considered the most vulnerable and consequently most in need of
adequate and affordable health insurance coverage.The authors' findings call
attention to the need to tailor communication strategies aimed at mitigating
health insurance literacy and, ultimately, access and outcomes disparities among
vulnerable populations in Israel and elsewhere. It also raises the importance of
creating insurance choice environments in health systems relying on consumers to
make coverage decisions that facilitate the decision process by using "choice
architecture" to, among other things, simplify plan information and highlight
meaningful differences between coverage options.
PMID- 28705192
TI - Medical condition and care of undocumented migrants in ambulatory clinics in Tel
Aviv, Israel: assessing unmet needs.
AB - BACKGROUND: Approximately 150,000 undocumented migrants (UM) who are medically
uninsured reside in Israel, including ~50,000 originating from the horn of Africa
(MHA). Free medical-care is provided by two walk-in clinics in Tel-Aviv. This
study aims to compare the medical complaints of UM from different origins, define
their community health needs and assess gaps between medical needs and available
services. METHODS: This cross-sectional study included a random sample of 610 UM
aged 18-64 years, who were treated in these community clinics between 2008 and
2011. The study compared UM who had complex medical conditions which necessitated
referral to more equipped medical settings with UM having mild/simple medical
conditions, who were treated at the clinics. RESULTS: MHA were younger,
unemployed and more commonly males compared with UM originating from other
countries. MHA also had longer referral-delays and visited the clinics less
frequently. UM with complex medical conditions were more commonly females, had
chronic diseases and demonstrated longer referral-delays than those who had
mild/simple medical conditions. The latter more commonly presented with
complained of respiratory, muscular and skeletal discomfort. In multivariate
analysis, the variables which predicted complex medical conditions included
female gender, chronic illnes and self-referral to the clinics. CONCLUSIONS: The
ambulatory clinics were capable of responding to mild/simple medical conditions.
Yet, the health needs of women and migrants suffering from complex medical
conditions and chronic diseases necessitated referrals to secondary/tertiary
medical settings, while jeopardizing the continuity of care. The health gaps can
be addressed by a more holistic social approach, which includes integration of UM
in universal health insurance.
PMID- 28705194
TI - Three recommendations to the new Director-General of the WHO on how to deliver
for girls and women.
PMID- 28705193
TI - Spatial regulation of monolignol biosynthesis and laccase genes control
developmental and stress-related lignin in flax.
AB - BACKGROUND: Bast fibres are characterized by very thick secondary cell walls
containing high amounts of cellulose and low lignin contents in contrast to the
heavily lignified cell walls typically found in the xylem tissues. To improve the
quality of the fiber-based products in the future, a thorough understanding of
the main cell wall polymer biosynthetic pathways is required. In this study we
have carried out a characterization of the genes involved in lignin biosynthesis
in flax along with some of their regulation mechanisms. RESULTS: We have first
identified the members of the phenylpropanoid gene families through a combination
of in silico approaches. The more specific lignin genes were further
characterized by high throughput transcriptomic approaches in different organs
and physiological conditions and their cell/tissue expression was localized in
the stems, roots and leaves. Laccases play an important role in the
polymerization of monolignols. This multigenic family was determined and a miRNA
was identified to play a role in the posttranscriptional regulation by cleaving
the transcripts of some specific genes shown to be expressed in lignified
tissues. In situ hybridization also showed that the miRNA precursor was expressed
in the young xylem cells located near the vascular cambium. The results obtained
in this work also allowed us to determine that most of the genes involved in
lignin biosynthesis are included in a unique co-expression cluster and that MYB
transcription factors are potentially good candidates for regulating these genes.
CONCLUSIONS: Target engineering of cell walls to improve plant product quality
requires good knowledge of the genes responsible for the production of the main
polymers. For bast fiber plants such as flax, it is important to target the
correct genes from the beginning since the difficulty to produce transgenic
material does not make possible to test a large number of genes. Our work
determined which of these genes could be potentially modified and showed that it
was possible to target different regulatory pathways to modify lignification.
PMID- 28705195
TI - Peto's Paradox: how has evolution solved the problem of cancer prevention?
AB - The risk of developing cancer should theoretically increase with both the number
of cells and the lifespan of an organism. However, gigantic animals do not get
more cancer than humans, suggesting that super-human cancer suppression has
evolved numerous times across the tree of life. This is the essence and promise
of Peto's Paradox. We discuss what is known about Peto's Paradox and provide
hints of what is yet to be discovered.
PMID- 28705196
TI - Better palliative care for people with a dementia: summary of interdisciplinary
workshop highlighting current gaps and recommendations for future research.
AB - BACKGROUND: Dementia is the most common neurological disorder worldwide and is a
life-limiting condition, but very often is not recognised as such. People with
dementia, and their carers, have been shown to have palliative care needs equal
in extent to those of cancer patients. However, many people with advanced
dementia are not routinely being assessed to determine their palliative care
needs, and it is not clear why this is so. MAIN BODY: An interdisciplinary
workshop on "Palliative Care in Neurodegeneration, with a focus on Dementia", was
held in Cork, Ireland, in May 2016. The key aim of this workshop was to discuss
the evidence base for palliative care for people with dementia, to identify
'gaps' for clinical research, and to make recommendations for interdisciplinary
research practice. To lead the discussion throughout the day a multidisciplinary
panel of expert speakers were brought together, including both researchers and
clinicians from across Ireland and the UK. Targeted invitations were sent to
attendees ensuring all key stakeholders were present to contribute to
discussions. In total, 49 experts representing 17 different academic and practice
settings, attended. Key topics for discussion were pre-selected based on
previously identified research priorities (e.g. James Lind Alliance) and
stakeholder input. Key discussion topics included: i. Advance Care Planning for
people with Dementia; ii. Personhood in End-of-life Dementia care; iii. Topics in
the care of advanced dementia at home. These topics were used as a starting
point, and the ethos of the workshop was that the attendees could stimulate
discussion and debate in any relevant area, not just the key topics, summarised
under iv. Other priorities. CONCLUSIONS: The care experienced by people with
dementia and their families has the potential to be improved; palliative care
frameworks may have much to offer in this endeavour. However, a solid evidence
base is required to translate palliative care into practice in the context of
dementia. This paper presents suggested research priorities as a starting point
to build this evidence base. An interdisciplinary approach to research and
priority setting is essential to develop actionable knowledge in this area.
PMID- 28705197
TI - Genetic polymorphism of scrA gene of Streptococcus mutans isolates is not
associated with biofilm formation in severe early childhood caries.
AB - BACKGROUND: To explore and analyse the association between biofilm and the
genetic polymorphisms of scrA gene of EnzymeIIscr found in clinical isolates of
Streptococcus mutans (S. mutans) from severe early childhood caries (S-ECC) in 3
years old children. METHODS: Clinical strains of S. mutans were conserved from a
previous study. Thirty strains of S. mutans from the S-ECC group and 30 strains
of S. mutans from the caries free (CF) group were selected. Biomass and viability
of biofilm formed by the strains were evaluated by crystal violet and alamar blue
assay. Genomic DNA was extracted from the S. mutans isolates. PCR was conducted
to amplify scrA gene. After purified and sequenced the PCR products, BioEdit
sofeware was used to analyse the sequence results. A chi-square test was used to
compare the results. RESULTS: Compared to the CF group, the biomass of S-ECC
group was higher (P = 0.0424). However, the viability of the two groups showed no
significant difference. All 60 clinically isolated S. mutans strains had a 1995
base pair (bp) scrA gene. Forty-nine point mutations were identified in scrA from
the 60 clinical isolates. There were 17 missense point mutations at the 10, 65,
103, 284, 289, 925, 1444, 1487, 1494, 1508, 1553, 1576, 1786, 1822, 1863, 1886,
and 1925 bp positions. The other 32 mutations were silent point mutations. No
positions were found at active sites of ScrA. The statistic analyse showed no
significant missense mutation rates between the two groups. CONCLUSIONS: There
was no association between biofilm and genetic polymorphisms of scrA from S.
mutans with S-ECC in 3 years old children.
PMID- 28705198
TI - Evaluation of a multiplex real-time PCR for detection of four bacterial agents
commonly associated with bovine respiratory disease in bronchoalveolar lavage
fluid.
AB - BACKGROUND: Pasteurella multocida, Mannheimia haemolytica, Histophilus somni and
Trueperella pyogenes are four bacterial agents commonly associated with bovine
respiratory disease (BRD). In this study a bacterial multiplex real-time PCR (the
RespoCheck PCR) was evaluated for the detection in bronchoalveolar lavage fluid
(BALF) of these four bacterial agents. RESULTS: The analytical sensitivity of the
multiplex real-time PCR assay determined on purified DNA and on bacterial cells
of the four target pathogens was one to ten fg DNA/assay and 4 * 10-1 to 2 * 100
CFU/assay. The analytical specificity of the test was, as evaluated on a
collection of 118 bacterial isolates, 98.3% for M. haemolytica and 100% for the
other three target bacteria. A set of 160 BALF samples of calves originating from
ten different herds with health problems related to BRD was examined with
bacteriological methods and with the RespoCheck PCR. Using bacteriological
examination as the gold standard, the diagnostic sensitivities and specificities
of the four bacterial agents were respectively between 0.72 and 1.00 and between
0.70 and 0.99. Kappa values for agreement between results of bacteriological
examination and PCRs were low for H. somni (0.17), moderate for P. multocida
(0.52) and M. haemolytica (0.57), and good for T. pyogenes (0.79). The low and
moderate kappa values seemed to be related to limitations of the bacteriological
examination, this was especially the case for H. somni. CONCLUSION: It was
concluded that the RespoCheck PCR assay is a valuable diagnostic tool for the
simultaneous detection of the four bacterial agents in BALF of calves.
PMID- 28705199
TI - The M-phase specific hyperphosphorylation of Staufen2 involved the cyclin
dependent kinase CDK1.
AB - BACKGROUND: Staufen2 (STAU2) is an RNA-binding protein involved in the post
transcriptional regulation of gene expression. This protein was shown to be
required for organ formation and cell differentiation. Although STAU2 functions
have been reported in neuronal cells, its role in dividing cells remains deeply
uncharacterized. Especially, its regulation during the cell cycle is completely
unknown. RESULTS: In this study, we showed that STAU2 isoforms display a mitosis
specific slow migration pattern on SDS-gels in all tested transformed and
untransformed cell lines. Deeper analyses in hTert-RPE1 and HeLa cells further
indicated that the slow migration pattern of STAU2 isoforms is due to
phosphorylation. Time course studies showed that STAU2 phosphorylation occurs
before prometaphase and terminates as cells exit mitosis. Interestingly, STAU2
isoforms were phosphorylated on several amino acid residues in the C-terminal
half via the cyclin-dependent kinase 1 (Cdk1), an enzyme known to play crucial
roles during mitosis. Introduction of phospho-mimetic or phospho-null mutations
in STAU2 did not impair its RNA-binding capacity, its stability, its interaction
with protein co-factors or its sub-cellular localization, suggesting that STAU2
phosphorylation in mitosis does not regulate these functions. Similarly, STAU2
phosphorylation is not likely to be crucial for cell cycle progression since
expression of phosphorylation mutants in hTert-RPE1 cells did not impair cell
proliferation. CONCLUSIONS: Altogether, these results indicate that STAU2
isoforms are phosphorylated during mitosis and that the phosphorylation process
involves Cdk1. The meaning of this post-translational modification is still
elusive.
PMID- 28705200
TI - The prognostic value of lymph node yield in the earliest stage of colorectal
cancer: a multicenter cohort study.
AB - BACKGROUND: In patients with stage II colorectal cancer (CRC) the number of
surgically retrieved lymph nodes (LNs) is associated with prognosis, resulting in
a minimum of 10-12 retrieved LNs being recommended for this stage. Current
guidelines do not provide a recommendation regarding LN yield in T1 CRC. Studies
evaluating LN yield in T1 CRC suggest that such high LN yields are not feasible
in this early stage, and a lower LN yield might be appropriate. We aimed to
validate the cut-off of 10 retrieved LNs on risk for recurrent cancer and
detection of LN metastasis (LNM) in T1 CRC, and explored whether this number is
feasible in clinical practice. METHODS: Patients diagnosed with T1 CRC and
treated with surgical resection between 2000 and 2014 in thirteen participating
hospitals were selected from the Netherlands Cancer Registry. Medical records
were reviewed to collect additional information. The association between LN yield
and recurrence and LNM respectively were analyzed using 10 LNs as cut-off.
Propensity score analysis using inverse probability weighting (IPW) was performed
to adjust for clinical and histological confounding factors (i.e., age, sex,
tumor location, size and morphology, presence of LNM, lymphovascular invasion,
depth of submucosal invasion, and grade of differentiation). RESULTS: In total,
1017 patients with a median follow-up time of 49.0 months (IQR 19.6-81.5) were
included. Four-hundred five patients (39.8%) had a LN yield >= 10. Forty-one
patients (4.0%) developed recurrence. LN yield >= 10 was independently associated
with a decreased risk for recurrence (IPW-adjusted HR 0.20; 95% CI 0.06-0.67; P =
0.009). LNM were detected in 84 patients (8.3%). LN yield >= 10 was independently
associated with increased detection of LNM (IPW-adjusted OR 2.27; 95% CI 1.39
3.69; P = 0.001). CONCLUSIONS: In this retrospective observational study,
retrieving < 10 LNs was associated with an increased risk of CRC recurrence,
advocating the importance to perform an appropriate oncologic resection of the
draining LNs and diligent LN search when patients with T1 CRC at high-risk for
LNM are referred for surgical resection. Given that both gastroenterologists,
surgeons and pathologists will encounter T1 CRCs with increasing frequency due to
the introduction of national screening programs, awareness on the consequences of
an inadequate LN retrieval is of utmost importance.
PMID- 28705201
TI - Genotypic diversity among multidrug resistant Pseudomonas aeruginosa and
Acinetobacter species at Mulago Hospital in Kampala, Uganda.
AB - BACKGROUND: Multidrug resistant Pseudomonas aeruginosa and Acinetobacter species
are common causes of nosocomial infections worldwide. Recently we reported the
occurrence of carbapenem resistant Enterobacteriaceae, P. aeruginosa and
Acinetobacter species at Mulago National Referral Hospital in Kampala, Uganda,
but the isolates were not analyzed for genetic relatedness. Herein we report the
intra-species genotypic diversity among P. aeruginosa and Acinetobacter baumannii
isolated from hospitalized patients and the environment at Mulago Hospital, using
repetitive elements-based PCR (Rep-PCR) genotyping. RESULTS: A total of 736
specimens from hospitalized patients were processed for culture and sensitivity
testing yielding 9 (1.2%) P. aeruginosa and 7 (0.95%) A. baumannii. Similarly,
100 samples from the hospital environment were processed yielding 33 (33%) P.
aeruginosa and 13 (13%) A. baumannii. Altogether, 62 non-repetitive isolates were
studied (42 P. aeruginosa and 20 A. baumannii), of which 38% (16/42) P.
aeruginosa and 40% (8/20) A. baumannii were multidrug resistant (isolates
resistant to three or more classes of antimicrobials). Carbapenem resistance
prevalence was 33 and 21% for P. aeruginosa from patients and the environment,
respectively, while it was 14 and 86% for A. baumannii from patients and
environment, respectively. Cluster analysis of the Rep-PCR fingerprints revealed
a high level of genetic diversity among the isolates within each species as few
isolates were clustered (at 100% level of similarity). More to this, the
clustered isolates revealed a complex nature of multidrug resistant P. aeruginosa
and A. baumannii clones circulating at Mulago Hospital. Importantly, certain
isolates from the environment and patients were clustered, implying that
hospitalized patients at Mulago were probably infected with strains from the
environment. CONCLUSIONS: The prevalence of multidrug resistant P. aeruginosa and
A. baumannii is high at Mulago Hospital but carbapenem resistance prevalence
remains relatively low in isolates from hospitalized patients. Importantly, the
prevalence of carbapenem resistance in isolates from the environment is high
implying the infection control practices at the hospital might be inadequate.
PMID- 28705202
TI - The influence of molecular markers and methods on inferring the phylogenetic
relationships between the representatives of the Arini (parrots, Psittaciformes),
determined on the basis of their complete mitochondrial genomes.
AB - BACKGROUND: Conures are a morphologically diverse group of Neotropical parrots
classified as members of the tribe Arini, which has recently been subjected to a
taxonomic revision. The previously broadly defined Aratinga genus of this tribe
has been split into the 'true' Aratinga and three additional genera, Eupsittula,
Psittacara and Thectocercus. Popular markers used in the reconstruction of the
parrots' phylogenies derive from mitochondrial DNA. However, current phylogenetic
analyses seem to indicate conflicting relationships between Aratinga and other
conures, and also among other Arini members. Therefore, it is not clear if the
mtDNA phylogenies can reliably define the species tree. The inconsistencies may
result from the variable evolution rate of the markers used or their weak
phylogenetic signal. To resolve these controversies and to assess to what extent
the phylogenetic relationships in the tribe Arini can be inferred from
mitochondrial genomes, we compared representative Arini mitogenomes as well as
examined the usefulness of the individual mitochondrial markers and the
efficiency of various phylogenetic methods. RESULTS: Single molecular markers
produced inconsistent tree topologies, while different methods offered various
topologies even for the same marker. A significant disagreement in these tree
topologies occurred for cytb, nd2 and nd6 genes, which are commonly used in
parrot phylogenies. The strongest phylogenetic signal was found in the control
region and RNA genes. However, these markers cannot be used alone in inferring
Arini phylogenies because they do not provide fully resolved trees. The most
reliable phylogeny of the parrots under study is obtained only on the
concatenated set of all mitochondrial markers. The analyses established
significantly resolved relationships within the former Aratinga representatives
and the main genera of the tribe Arini. Such mtDNA phylogeny can be in agreement
with the species tree, owing to its match with synapomorphic features in plumage
colouration. CONCLUSIONS: Phylogenetic relationships inferred from single
mitochondrial markers can be incorrect and contradictory. Therefore, such
phylogenies should be considered with caution. Reliable results can be produced
by concatenated sets of all or at least the majority of mitochondrial genes and
the control region. The results advance a new view on the relationships among the
main genera of Arini and resolve the inconsistencies between the taxa that were
previously classified as the broadly defined genus Aratinga. Although gene and
species trees do not always have to be consistent, the mtDNA phylogenies for
Arini can reflect the species tree.
PMID- 28705203
TI - Serum lactate is an independent predictor of hospital mortality in critically ill
patients in the emergency department: a retrospective study.
AB - BACKGROUND: Elevated lactate has been found to be associated with a higher
mortality in a diverse patient population. The aim of the study is to investigate
if initial serum lactate level is independently associated with hospital
mortality for critically ill patients presenting to the Emergency Department.
METHODS: Single-center, retrospective study at a tertiary care hospital looking
at patients who presented to the Emergency Department (ED) between 2014 and 2016.
A total of 450 patients were included in the study. Patients were stratified to
lactate levels: <2 mmol/L, 2-4 mmol/L and >4 mmol/L. The primary outcome was in
hospital mortality. Secondary outcomes included 72-h hospital mortality, ED and
hospital lengths of stay. RESULTS: The mean age was 64.87 +/- 18.08 years in the
<2 mmol/L group, 68.51 +/- 18.01 years in the 2-4 mmol/L group, and 67.46 +/-
17.67 years in the >4 mmol/L group. All 3 groups were comparable in terms of age,
gender and comorbidities except for diabetes, with the 2-4 mmol/L and >4 mmol/L
groups having a higher proportion of diabetic patients. The mean lactate level
was 1.42 +/- 0.38 (<2 mmol/L), 2.72 +/- 0.55 (2-4 mmol/L) and 7.18 +/- 3.42 (>4
mmol/L). In-hospital mortality was found to be 4 (2.7%), 18(12%) and 61(40.7%)
patients in the low, intermediate and high lactate groups respectively. ED and
hospital length of stay were longer for the >4 mmol/L group as compared to the
other groups. While adjusting for all variables, patients with intermediate and
high lactate had 7.13 (CI 95% 2.22-22.87 p = 0.001) and 29.48 (CI 95% 9.75-89.07
p = <0.001) greater odds of in-hospital mortality respectively. DISCUSSION: Our
results showed that for all patients presenting to the ED, a rising lactate value
is associated with a higher mortality. This pattern was similar regardless of
patients' age, presence of infection or blood pressure at presentation.
CONCLUSION: Higher lactate values are associated with higher hospital mortalities
and longer ED and hospital lengths of stays. Initial ED lactate is a useful test
to risk-stratify critically ill patients presenting to the ED.
PMID- 28705204
TI - Delay along the care-seeking journey of patients with ocular surface squamous
neoplasia in Kenya.
AB - BACKGROUND: In Africa, accessing eye health services is a major challenge. Ocular
surface squamous neoplasia (OSSN) is a substantial ocular health problem in
Africa related to solar UV light exposure and HIV infection among other risk
factors. The disease causes visual loss and even death in advanced cases. This
study was conducted to assess referral pathway and treatment delay for patients
with OSSN in Kenya. METHODS: Adults with conjunctival lesions presenting to four
eye centres were asked about their occupations, when they noticed the growth,
health facilities visited in seeking care, cost of consultation, surgery,
medicines and histopathology and dates at each step. The time-to-presentation was
divided into quartiles and correlates analysed using ordinal logistic regression.
RESULTS: We evaluated 158 first-time presenters with OSSN. Most were women (102
[65%]), living with HIV (78/110 tested [71%]), with low to medium income (127
[80%]). Most of the HIV patients (49/78 [63%]) were in antiretroviral care
programs. About half (88/158, [56%]) presented directly to the study centres
while the rest were referred. Indirect presenters sought care earlier than direct
presenters (median 2.0 months vs 5.5 months) and travelled a shorter distance to
the first health facility (median 20 km vs 30 km) but had surgery later (median
12.5 months vs 5.5 months). Visits beyond the first health facility for indirect
presenters markedly increased delay (median 7.3, 29.0, 37.9, and 32.0 months for
1-4 facilities, respectively). Delay was associated with number of health
facilities visited (adjusted ordered OR = 9.12; 95%CI 2.83-29.4, p < 0.001) and
being female (adjusted ordered OR = 2.42; 95%CI 1.32-4.44, p = 0.004). At the
time of presentation at the study centres for surgery the median tumour diameter
in both directly and indirectly presenting patients was 6 mm (p = 0.52) and the
histological spectrum of OSSN was similar between the groups (p = 0.87).
CONCLUSIONS: Referral delays definitive treatment for OSSN. Women were more
likely to experience delay. Despite regular contact with the health system for
those with known HIV infection, delays occurred. Early detection and referral of
OSSN in the HIV service might reduce delays, but reassuringly delay did not give
rise to a larger proportion with more advanced grade of OSSN.
PMID- 28705205
TI - Clinicopathological features and prognosis of gastroenteropancreatic
neuroendocrine neoplasms in a Chinese population: a large, retrospective single
centre study.
AB - BACKGROUND: Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are the
most common type of neuroendocrine tumors, accounting for more than half of
neuroendocrine neoplasms (NENs). We performed a retrospective study in our center
to investigate the clinicopathological features, risk factors of metastasis, and
prognosis of GEP-NENs in a Chinese population. METHODS: Four hundred forty
patients with GEP-NENs treated at the First Affiliated Hospital of Zhengzhou
University between January 2011 and March 2016 were analyzed retrospectively.
Multivariate logistic regression was performed to identify independent risk
factors for metastasis of the tumors. The Kaplan-Meier method was used for
survival analysis, and log-rank tests for comparisons among groups. RESULTS:
Primary sites were the stomach (24.3%), rectum (24.1%), pancreas (20.5%),
esophagus (12.3%), unknown primary origin (UPO-NEN) (8.0%), duodenum (6.1%).
Three hundred eighty-nine of the 440 GEP-NENs cases (88.4%) were non-functional
tumors, and patients had non-specific symptoms, which could have led to delay in
diagnosis and treatment. Neuroendocrine tumor, neuroendocrine carcinoma, and
mixed adenoendocrine carcinoma were 56.8%, 33.2% and 3.2%, respectively, of the
cases. One hundred thirty (29.5%) of the tumors were G1, 120 (27.3%) G2, and 190
(43.2%) G3. The immunohistochemical positive rate of synaptophysin was 97.7% and
of chromogranin 48.7%. Logistic regression analysis revealed that the diameter
and pathological classification of tumors were the most important predictors for
metastasis. The median survival time was 34 months for patients with well
differentiated neuroendocrine tumors grade G3 and 11 months for poorly
differentiated neuroendocrine carcinoma. The median survival time of patients
with localized disease, regional disease, and distant disease was 36 months, 15
month, and 6 months, respectively. CONCLUSIONS: This study constitutes a
comprehensive analysis of the clinicopathological features of GEP-NENs in a
Chinese population. GEP-NENs may occur at any part of the digestive system. The
diameter and pathological classification of tumor are the most important
predictors for metastasis. The prognosis is poor for patients with poorly
differentiated neuroendocrine cancers and distant metastases.
PMID- 28705206
TI - Digital evaluation of nasal changes induced by rapid maxillary expansion with
different anchorage and appliance design.
AB - BACKGROUND: Scientific evidence showed that rapid maxillary expansion (RME)
affects naso-maxillary complex, increasing nasal width and volume. This study
aimed to evaluate nasal changes induced by rapid maxillary expansion with
different anchorage and appliance design by using low dose and cone beam computed
tomography. METHODS: A total of 44 patients (20 males, mean age 8y 8 m +/- 1y 2
m; 24 females mean age 8y 2 m +/- 1y 4 m) were included in the investigation and
divided into three groups according to the appliance: Hyrax-type expander
anchored to permanent teeth, modified Hyrax-type expander anchored to deciduous
teeth, modified Haas-type expander anchored to deciduous teeth. Maxillary
expansion was performed until overcorrection and the expander was passively kept
in situ for 7 months at least. All patients had three-dimensional imaging before
expansion (T0) and after the retention period (T1). Nasal floor width, nasal wall
width, maxillary inter-molar width were measured by means of Mimics software. The
paired sample t-test was employed to assess the significance of the differences
between the time points; the analysis of variance test (ANOVA) was used to
compare differences between groups. RESULTS: The statistical analysis revealed
significant differences between T0 and T1 for each recorded measurement in each
group; no significant differences were found by comparing groups. CONCLUSIONS:
Rapid maxillary expansion produces a significant skeletal transverse expansion of
nasal region in growing patients. No significant differences in nasal effects are
expected when the appliance is anchored onto deciduous teeth, with or without the
palatal acrylic coverage.
PMID- 28705207
TI - Development and pilot testing of an interprofessional patient-centered team
training programme in medical rehabilitation clinics in Germany: a process
evaluation.
AB - BACKGROUND: Interprofessional teamwork is considered to be a key component of
patient-centred treatment in healthcare, and especially in the rehabilitation
sector. To date, however, no interventions exist for improving teamwork in
rehabilitation clinics in Germany. A team training programme was therefore
designed that is individualised in content but standardised regarding methods and
process. It is clinic specific, task related, solution focused and context
oriented. The aim of the study was to implement and evaluate this training for
interprofessional teams in rehabilitation clinics in Germany. METHODS: The
measure consists of a training of a varying number of sessions with
rehabilitation teams that consists of four distinct phases. Those are undergone
chronologically, each with clinic-specific contents. It was implemented between
2013 and 2014 in five rehabilitation clinics in Germany and evaluated by the
participants via questionnaire (n = 52). RESULTS: Staff in three clinics
evaluated the programme as helpful, in particular rating moderation, discussions
and communication during the training positively. Staff in the remaining two
clinics rated it as not very or not helpful and mentioned long-term structural
problems or a lack of need for team training as a reason for this. CONCLUSIONS:
The team training is applicable and accepted by staff. It should, however, be
tested in a greater sample and compared with a control group. Processes should be
studied in more detail in order to determine what differentiates successful from
non-successful interventions and the different requirements each of these might
have.
PMID- 28705208
TI - Testing feedback message framing and comparators to address prescribing of high
risk medications in nursing homes: protocol for a pragmatic, factorial, cluster
randomized trial.
AB - BACKGROUND: Audit and feedback (AF) interventions that leverage routine
administrative data offer a scalable and relatively low-cost method to improve
processes of care. AF interventions are usually designed to highlight
discrepancies between desired and actual performance and to encourage recipients
to act to address such discrepancies. Comparing to a regional average is a common
approach, but more recipients would have a discrepancy if compared to a higher
than-average level of performance. In addition, how recipients perceive and
respond to discrepancies may depend on how the feedback itself is framed. We aim
to evaluate the effectiveness of different comparators and framing in feedback on
high-risk prescribing in nursing homes. METHODS: This is a pragmatic, 2 * 2
factorial, cluster-randomized controlled trial testing variations in the
comparator and framing on the effectiveness of quarterly AF in changing high-risk
prescribing in nursing homes in Ontario, Canada. We grouped homes that share
physicians into clusters and randomized these clusters into the four experimental
conditions. Outcomes will be assessed after 6 months; all primary analyses will
be by intention-to-treat. The primary outcome (monthly number of high-risk
medications received by each patient) will be analysed using a general linear
mixed effects regression model. We will present both four-arm and factorial
analyses. With 160 clusters and an average of 350 beds per cluster, assuming no
interaction and similar effects for each intervention, we anticipate 90% power to
detect an absolute mean difference of 0.3 high-risk medications prescribed. A
mixed-methods process evaluation will explore potential mechanisms underlying the
observed effects, exploring targeted constructs including intention, self
efficacy, outcome expectations, descriptive norms, and goal prioritization. An
economic analysis will examine cost-effectiveness analysis from the perspective
of the publicly funded health care system. DISCUSSION: This protocol describes
the rationale and methodology of a trial testing manipulations of theory-informed
components of an audit and feedback intervention to determine how to improve an
existing intervention and provide generalizable insights for implementation
science. TRIAL REGISTRATION: NCT02979964.
PMID- 28705209
TI - Metabolic characteristics of individuals at a high risk of type 2 diabetes - a
comparative cross-sectional study.
AB - BACKGROUND: Type 2 diabetes (T2D) is associated with substantial morbidity and
mortality. Individuals with a family history of T2D are at an increased risk of
developing the disease. The aim of this study was to assess metabolic differences
between first-degree relatives (FDR) of T2D patients and persons with no known
family history of T2D (non-FDR). METHODS: In 200 FDR and 73 non-FDR, we compared
anthropometrics, glucose tolerance status, different measurements of insulin
secretion, insulin resistance, as well as blood lipids and other blood analyses.
RESULTS: In the FDR group, 30 individuals had impaired glucose tolerance or T2D.
Among the non-FDR, two individuals had impaired glucose tolerance. In unadjusted
data, the FDR were older, had stronger heredity for coronary heart disease, lower
body mass index and weight, higher OGTT plasma glucose concentrations, and
impaired insulin secretion (all p < 0.05). Using propensity score, we matched the
groups, resulting in significantly stronger heredity of coronary heart disease,
higher OGTT plasma glucose at 60 and 90 min, larger glucose area under curve
during the OGTT and higher serum creatinine among the FDR. Using least squares
means, OGTT glucose at 60 and 120 min, as well as the area under curve, and OGTT
insulin levels at 60 min were significantly higher. Body mass index was
negatively correlated with insulin sensitivity (MI) and positively correlated
with HOMA-beta, a measurement of insulin secretion. CONCLUSIONS: We show that FDR
are more likely to have impaired glucose tolerance and display higher OGTT plasma
glucose and insulin, indicating an unfavorable metabolic profile. We conclude
that OGTT is a simple and yet informative metabolic assessment in the FDR group.
In both groups, we saw a negative correlation between body mass index and MI,
confirming the role of body mass index in insulin resistance.
PMID- 28705210
TI - Transcutaneous electrical stimulation of somatic afferent nerves in the foot
relieved symptoms related to postoperative bladder spasms.
AB - BACKGROUND: Bladder spasm is a common side effect of urological surgery. Main
treatment modalities include opioids or anticholinergic medication; however,
bladder spasms still occur even after these interventions. Recent studies
indicate that transcutaneous stimulation of the foot can result in 50% increase
in bladder capacity in healthy adults, and inhibit bladder detrusor overactivity
in spinal cord injured patients. In this study, we examined the effects of
transcutaneous electrical stimulation of the foot on bladder spasms related
symptoms. METHODS: Sixty-six male patients who underwent prostate or bladder
surgeries due to benign prostatic hyperplasia or bladder diseases were randomly
divided into two groups: the control group (n = 36) and the treatment group (n =
30). The control group received the routine postoperative care. The treatment
group received daily transcutaneous electrical stimulation of the foot during 3
days after surgery; each time lasted for 60 min. All patients were evaluated by
the Visual Analogue Scale for pain sensation, frequency of bladder spasm
episodes, and a total score of bladder spasms symptoms. RESULTS: In the control
group, the patients with bladder surgery had a higher Visual Analogue Scale score
than patients with prostate surgery (P = 0.024). In both treatment and control
groups, the Visual Analogue Scale score, spasm frequency, and total score of
bladder spasm symptoms decreased from day 1 to day 3 (P <0.001). The Visual
Analogue Scale score at day 2, total score of bladder spasm symptoms at day 2 and
day 3 were significantly lower in the treatment group than in the control group
(P <0.05). CONCLUSION: These results provided preliminary evidence suggesting
beneficial effects of stimulating somatic afferent nerves in the foot on
postoperative bladder spasms. TRIAL REGISTRATION: The study was registered with
Chinese Clinical Trial Registry on June 13 2016 ( http://www.chictr.org.cn/ )
(Identifier: ChiCTR-INR-16008635).
PMID- 28705211
TI - Streptococcal toxic-shock syndrome due to Streptococcus dysgalactiae subspecies
equisimilis in breast cancer-related lymphedema: a case report.
AB - BACKGROUND: Breast cancer-related lymphedema often causes cellulitis and is one
of the most common complications after breast cancer surgery. Streptococci are
the major pathogens underlying such cellulitis. Among the streptococci, the
importance of the Lancefield groups C and G is underappreciated; most cases
involve Streptococcus dysgalactiae subspecies equisimilis. Despite having a
relatively weak toxicity compared with group A streptococci, Streptococcus
dysgalactiae subspecies equisimilis is associated with a mortality rate that is
as high as that of group A streptococci in cases of invasive infection because
Streptococcus dysgalactiae subspecies equisimilis mainly affects elderly
individuals who already have various comorbidities. CASE PRESENTATION: An 83-year
old Japanese woman with breast cancer-related lymphedema in her left upper limb
was referred to our hospital with high fever and acute pain with erythema in her
left arm. She showed septic shock with disseminated intravascular coagulation.
Blood culture showed positive results for Streptococcus dysgalactiae subspecies
equisimilis, confirming a diagnosis of streptococcal toxic-shock syndrome. She
survived after successful intensive care. CONCLUSIONS: To the best of our
knowledge, this case represents the first report of Streptococcus dysgalactiae
subspecies equisimilis-induced streptococcal toxic-shock syndrome in a patient
with breast cancer-related lymphedema. Breast cancer-related lymphedema is a
common problem, and we must pay attention to invasive streptococcal soft tissue
infections, particularly in elderly patients with chronic disease.
PMID- 28705212
TI - Moringa isothiocyanate complexed with alpha-cyclodextrin: a new perspective in
neuroblastoma treatment.
AB - BACKGROUND: Several lines of evidence suggest the consume of natural products for
cancer prevention or treatment. In particular, isothiocyanates (ITCs) exerting
anti-cancer properties, have received great interest as potential
chemotherapeutic agents. This study was designed to assess the anti-proliferative
activities of a new preparation of Moringa oleifera-derived 4-(alpha-L
rhamnopyranosyloxy)benzyl ITC (moringin) complexed with alpha-cyclodextrin
(moringin + alpha-CD; MAC) on SH-SY5Y human neuroblastoma cells. This new
formulation arises in the attempt to overcome the poor solubility and stability
of moringin alone in aqueous media. METHODS: SH-SY5Y cells were cultured and
exposed to increasing concentrations of MAC (1.0, 2.5 and 5.0 MUg). Cell
proliferation was examined by MTT and cell count assays. The cytotoxic activity
of the MAC complex was assessed by lactate dehydrogenase (LDH) assay and trypan
blue exclusion test. In addition, western blotting analyses for the main
apoptosis-related proteins were performed. RESULTS: Treatment of SH-SY5Y cells
with the MAC complex reduced cell growth in concentration dependent manner.
Specifically, MAC exhibited a potent action in inhibiting the PI3K/Akt/mTOR
pathway, whose aberrant activation was found in many types of cancer. MAC was
also found to induce the nuclear factor-kappaB (NF-kappaB) p65 activation by
phosphorylation and its translocation into the nucleus. Moreover, treatment with
MAC was able to down-regulate MAPK pathway (results focused on JNK and p38
expression). Finally, MAC was found to trigger apoptotic death pathway (based on
expression levels of cleaved-caspase 3, Bax/Bcl-2 balance, p53 and p21).
CONCLUSION: These findings suggest that use of MAC complex may open novel
perspectives to improve the poor prognosis of patients with neuroblastoma.
PMID- 28705213
TI - The therapeutic landscape of HIV-1 via genome editing.
AB - Current treatment for HIV-1 largely relies on chemotherapy through the
administration of antiretroviral drugs. While the search for anti-HIV-1 vaccine
remain elusive, the use of highly active antiretroviral therapies (HAART) have
been far-reaching and has changed HIV-1 into a manageable chronic infection.
There is compelling evidence, including several side-effects of ARTs, suggesting
that eradication of HIV-1 cannot depend solely on antiretrovirals. Gene therapy,
an expanding treatment strategy, using RNA interference (RNAi) and programmable
nucleases such as meganuclease, zinc finger nuclease (ZFN), transcription
activator-like effector nuclease (TALEN), and clustered regularly interspaced
short palindromic repeats/CRISPR-associated proteins (CRISPR-Cas9) are
transforming the therapeutic landscape of HIV-1. TALENS and ZFNS are structurally
similar modular systems, which consist of a FokI endonuclease fused to custom
designed effector proteins but have been largely limited, particularly ZFNs, due
to their complexity and cost of protein engineering. However, the newly developed
CRISPR-Cas9 system, consists of a single guide RNA (sgRNA), which directs a Cas9
endonuclease to complementary target sites, and serves as a superior alternative
to the previous protein-based systems. The techniques have been successfully
applied to the development of better HIV-1 models, generation of protective
mutations in endogenous/host cells, disruption of HIV-1 genomes and even
reactivating latent viruses for better detection and clearance by host immune
response. Here, we focus on gene editing-based HIV-1 treatment and research in
addition to providing perspectives for refining these techniques.
PMID- 28705214
TI - Demographic and clinical characteristics of carbon monoxide poisoning: nationwide
data between 1999 and 2012 in Taiwan.
AB - BACKGROUND: Carbon monoxide poisoning (COP) is not uncommon, but nationwide
epidemiological data are limited. We conducted a study in Taiwan to fill the data
gaps. METHODS: We used a nationwide poisoning database to study all COP patients
in Taiwan diagnosed between 1999 and 2012. We conducted descriptive analyses and
compared the differences between the two sexes. In addition, we assessed the
trends in suicide and mortality rates from 1999 to 2012. RESULTS: We identified
25,912 COP patients with an almost equal female and male distribution (50.6% vs.
49.4%). The mean age was 36.0 years, and most of the patients were between 20 and
50 years old. The highest incidence rate in the year occurred during winter.
While female patients were more likely to have mental disorders (35.9% vs. 28.1%,
p < 0.001), male patients were more likely to be resulted from suicide attempts
(22.9% vs. 17.7%, p < 0.001). In both sexes, the suicidal rate increased from
1999, reached the peak in 2007, and then decreased gradually. Hyperbaric oxygen
therapy was performed in 24.2% of the patients. Neurological sequelae developed
in 9.1% of the patients, and chronic respiratory failure and requirement of long
term care were observed in 5.0% and 0.1% of the patients. The 1-month and 3-month
mortality rates were 1.6% and 5.0%. The 3-month mortality rate did not show
significant change between 1999 and 2012. DISCUSSION: This study showed a whole
picture of COP in Taiwan, which could add to the important knowledge of this
disastrous problem in public health. CONCLUSION: Some important findings,
including higher percentages of mental disorders in female patients and suicide
attempt in male patients, seasonal changes, and trends in mortality and morbidity
(suicide) rates, may help developing strategies for prevention and treatment of
COP.
PMID- 28705215
TI - Feasibility of district wide screening of health care workers for tuberculosis in
Zambia.
AB - BACKGROUND: Many health care workers (HCWs) are at increased risk for
tuberculosis (TB). The World Health Organization (WHO) recommends screening HCWs
for TB in high burden settings but this is often not implemented in countries
with a high TB incidence. We assessed the feasibility of TB screening among HCWs,
including participation rate and yield, as part of a project introducing facility
specific TB interventions. METHODS: This study had a cross-sectional design. HCWs
(including paid staff and community volunteers) from 13 clinics and two hospitals
in the Ndola district of Zambia participated. HCWs were screened by a designated
person in their own facility. The agreed screening algorithm for HCWs included
annual symptom screening, with sputum smear, culture (or Xpert) and chest x-ray
offered to HCWs with at least one TB symptom, i.e. those with presumptive TB.
RESULTS: A total of 1011 out of 1619 (62%) staff and 71 out of 138 (51%)
community volunteers were screened within one year, total 1082/1757 (62%). Five
percent (52/1082) of those screened were presumptive TB patients. Seventy-three
percent (38/52) of presumptive TB patients received all diagnostic tests
according to the agreed algorithm. Eighteen out of 1757 staff and volunteers
combined were diagnosed with TB within a calendar year, showing a notified TB
incidence of 1%. At least five of them were diagnosed during the screening
appointment (0.5% of those screened). One of the 18 HCWs died of TB. Seventy-six
percent (822/1082) of screened HCWs indicated that they already knew their HIV
status. Screening was considered feasible if confidentiality can be guaranteed
although challenges such as the time required for screening and sample transport
were reported. CONCLUSIONS: It is feasible to conduct and implement screening
programs for TB among HCWs in hospitals and clinics, and the notified incidence
and yield is high. Advocacy is needed to educate managers and HCWs on the
importance of screening and the implementation of locally relevant screening
algorithms. It is essential to ensure access to TB infection control,
diagnostics, treatment and confidential registration for HCW.
PMID- 28705216
TI - Surgical management of Hawkins type III talar neck fracture through the approach
of medial malleolar osteotomy and mini-plate for fixation.
AB - BACKGROUND: Fractures of the talar neck are relatively uncommon yet current
interventions suffer from a high incidence of complications and poor functional
outcomes. In the present study, we report a surgical treatment of Hawkins type
III talar neck fracture through the approach of medial malleolar osteotomy and
mini-plate for fixation and discuss the therapeutic effects after long-term
follow-up. METHODS: From January 2010 to January 2015, 21 patients with 22
fractures were treated using this approach within days of sustaining the injury.
Clinical and radiographic data were collected during regular post-operative
follow-ups. Health-related quality of life factors were evaluated using visual
analogue scale (VAS). Functional outcomes were determined according the Hawkins
score and the Ankle-Hind foot Scale of the American Orthopedic Foot and Ankle
Society (AOFAS). Present of complications such as arthritis, avascular necrosis
(AVN), and malunion were evaluated using radiographs and magnetic resonance
imaging (MRI). Anatomical parameters of injured and corresponding uninjured talus
were measured and compared using digital three-dimensional (3D) computer model.
RESULTS: The mean duration of surgery was 65.6 +/- 9.7 min. The average blood
loss volume of the patients was 29.1 +/- 5.7 ml. All the patients except 1 were
followed up 18 to 41 months (average 29.6 months). The average VAS score for
these patients was 3.2 +/- 1.1, and the mean Hawkins score was 11.4 +/- 3.4 at
the final follow-up visit. The average AOFAS score was 72.8 +/- 17.3. Nine
patients outcomes were rated as "excellent", 4 as "good", 4 as "fair," and 4 as
"poor". No malunion, screw loosening, plate breakage, or other internal fixation
failures were found at final follow-up. Long-term complications included: 1 case
of malunion, 5 cases of complete AVN, 8 cases of partial AVN, 13 cases of
talocrural arthritis, 14 cases of subtalar arthritis, and 3 cases of
talonavicular arthritis. Secondary surgery was performed in 4 cases. The relevant
average anatomical data of injured and uninjured talus show no significant
difference. CONCLUSIONS: This surgical treatment we used here resulted in
decreased soft tissue trauma, adequate exposure of talar neck, satisfactory
performance of daily life activities, and quality of life following surgery and
restoration of anatomy of injured talus. However, long-term complications such as
arthritis and AVN are still commonly seen.
PMID- 28705217
TI - Monitoring clinical and microbiological evolution of a cystic fibrosis patient
over 26 years: experience of a Brazilian CF Centre.
AB - BACKGROUND: Burkholderia cepacia complex is a group of opportunistic pathogens in
cystic fibrosis (CF) patients believed to be associated with poor prognosis and
patient-to-patient transmissibility. Little is known about clinical outcomes
after B. vietnamiensis chronic colonization/infection. CASE PRESENTATION: A 33 yo
male patient had diagnosis of CF by 7 yo, after recurrent pneumonia during
infancy and lobectomy (left upper lobe) at 6 yo. Burkholderia cepacia complex
(Bcc) was first isolated by 13 yo, and the patient fulfilled the criteria for
chronic colonization by 15 yo. In the following 16 years (1997-2013), there was
intermittent isolation of P. aeruginosa and continuous isolation of Bcc,
identified as B. vietnamiensis. There was clinical and laboratorial stability for
16 years with annual rate of decline in forced expiratory volume in 1 s (FEV1)
and forced vital capacity (FVC) of 1.61 and 1.35%, respectively. From 2013 to
2015, there was significant clinical and lung function deterioration: annual rate
of decline in FEV1 and FVC was 3 and 4.1%, respectively while body mass index
decreased from 18.1 to 17.1. Episodes of hemoptysis and respiratory exacerbations
(with hospital admissions) became more frequent. CF related diabetes was
diagnosed (fasting glycemia: 116 mg/dL, oral glucose tolerance test: 305 mg/dL).
Because of the severity of the disease in the last years, in addition to
traditional microbiological surveillance, microbiome analysis by next generation
sequencing (NGS) was performed on respiratory secretions. The NGS showed that 97%
of the sequencing data were attributed to genus Burkholderia. CONCLUSIONS: We
report the case of a 33-year-old male CF patient known to have chronic infection
with B. vietnamiensis who remained clinically stable for 16 years and presented
recent clinical and laboratorial deterioration. Microbiome analysis of
respiratory secretions was performed in 3 samples collected in 2014-2015.
Clinical deterioration overlapped with cystic fibrosis-related diabetes and
microbiome composition revealed no significant differences when compared
microbiome results to culture dependent methods.
PMID- 28705218
TI - Radiotherapy among nonagenarians with anal or rectal carcinoma: should we avoid
or adapt treatment?
PMID- 28705219
TI - Erratum to: RERG suppresses cell proliferation, migration and angiogenesis
through ERK/NF-kappaB signaling pathway in nasopharyngeal carcinoma.
PMID- 28705220
TI - The role of sports clubs in helping older people to stay active and prevent
frailty: a longitudinal mediation analysis.
AB - BACKGROUND: Frailty is a common syndrome in older adults characterised by
increased vulnerability to adverse health outcomes as a result of decline in
functional and physiological measures. Frailty predicts a range of poor health
and social outcomes and is associated with increased risk of hospital admission.
The health benefits of sport and physical activity and the health risks of
inactivity are well known. However, less is known about the role of sports clubs
and physical activity in preventing and managing frailty in older adults. The
objective of this study is to examine the role of membership of sports clubs in
promoting physical activity and reducing levels of frailty in older adults.
METHODS: We used data from waves 1 to 7 of the English Longitudinal Study of
Ageing (ELSA). Survey items on physical activity were combined to produce a
measure of moderate or vigorous physical activity for each wave. Frailty was
measured using an index of accumulated deficits. A total of sixty deficits,
including symptoms, disabilities and diseases were recorded through self-report
and tests. Direct and indirect relationships between sports club membership,
levels of physical activity and frailty were examined using a cross-lagged panel
model. RESULTS: We found evidence for an indirect relationship between sports
club membership and frailty, mediated by physical activity. This finding was
observed when examining time-specific indirect pathways and the total of all
indirect pathways across seven waves of survey data (Est = -0.097 [95% CI =
0.124,-0.070], p = <0.001). CONCLUSIONS: These analyses provide evidence to
suggest that sports clubs may be useful in preventing and managing frailty in
older adults, both directly and indirectly through increased physical activity
levels. Sports clubs accessible to older people may improve health in this
demographic by increasing activity levels and reducing frailty and associated
comorbidities. There is a need for investment in these organisations to provide
opportunities for older people to achieve the levels of physical activity
necessary to prevent health problems associated with inactivity.
PMID- 28705221
TI - Viral manipulation of the cellular sumoylation machinery.
AB - Viruses exploit various cellular processes for their own benefit, including
counteracting anti-viral responses and regulating viral replication and
propagation. In the past 20 years, protein sumoylation has emerged as an
important post-translational modification that is manipulated by viruses to
modulate anti-viral responses, viral replication, and viral pathogenesis. The
process of sumoylation is a multi-step cascade where a small ubiquitin-like
modifier (SUMO) is covalently attached to a conserved PsiKxD/E motif within a
target protein, altering the function of the modified protein. Here we review how
viruses manipulate the cellular machinery at each step of the sumoylation process
to favor viral survival and pathogenesis.
PMID- 28705222
TI - Weekend warrior physical activity pattern and common mental disorder: a
population wide study of 108,011 British adults.
AB - BACKGROUND: The dose-response association between physical activity (PA) and
mental health is poorly described. We explored cross-sectional associations
between physical activity and common mental disorder (psychological distress) in
'weekend warriors' who do all their exercise in one or two sessions per week.
METHODS: Adult participants (n = 108,011, age = 47 +/- 17 yrs., 46.5% men) were
recruited from general population household-based surveys (Health Survey for
England and Scottish Health Survey) from 1994 to 2004. Data were pooled and
analyzed using logistic regression models. Moderate to vigorous physical activity
(MVPA) was self-reported and psychological distress was measured using the 12
item General Health Questionnaire (GHQ-12). RESULTS: Psychological distress (GHQ
12 > 3) was prevalent in 14.5% of the sample. In healthy participants an inverse
association between PA and psychological distress was optimal at the PA guideline
(150 mins/wk. MVPA or 75 min/wk. Vigorous PA) regardless of whether it was
accumulated in one or two bouts per week "Weekend warrior" (odd ratio = 0.68, 95%
CI, 0.63, 0.73) or as more frequent daily bouts (odd ratio = 0.68, 95% CI, 0.64,
0.72) in comparison to the inactive reference group. In participants with chronic
health conditions an inverse association between PA and psychological distress
was also evident at lower doses (one or two sessions of PA a week below PA
guideline) (OR = 0.72, 95% CI, 0.68, 0.77). Undertaking vigorous intensity PA as
part of the PA guideline conferred additional benefit in women (odds ratio =
0.87, 95% CI, 0.75, 1.00), but not men. CONCLUSION: Mental health benefits may be
accrued through different PA patterns, thus individual approaches to prescribing
exercise should be promoted.
PMID- 28705223
TI - Improving preventive health care in Aboriginal and Torres Strait Islander primary
care settings.
AB - BACKGROUND: Like other colonised populations, Indigenous Australians experience
poorer health outcomes than non-Indigenous Australians. Preventable chronic
disease is the largest contributor to the health differential between Indigenous
and non-Indigenous Australians, but recommended best-practice preventive care is
not consistently provided to Indigenous Australians. Significant improvement in
health care delivery could be achieved through identifying and minimising
evidence-practice gaps. Our objective was to use clinical audit data to create a
framework of the priority evidence-practice gaps, strategies to address them, and
drivers to support these strategies in the delivery of recommended preventive
care. METHODS: De-identified preventive health clinical audit data from 137
primary health care (PHC) centres in five jurisdictions were analysed (n = 17,108
audited records of well adults with no documented major chronic disease; 367
system assessments; 2005-2014), together with stakeholder survey data relating to
interpretation of these data, using a mixed-methods approach (n = 152 responses
collated in 2015-16). Stakeholders surveyed included clinicians, managers, policy
officers, continuous quality improvement (CQI) facilitators and academics.
Priority evidence-practice gaps and associated barriers, enablers and strategies
to address the gaps were identified and reported back through two-stages of
consultation. Further analysis and interpretation of these data were used to
develop a framework of strategies and drivers for health service improvement.
RESULTS: Stakeholder identified priorities were: following-up abnormal test
results; completing cardiovascular risk assessments; timely recording of results;
recording enquiries about living conditions, family relationships and substance
use; providing support for clients identified with emotional wellbeing risk;
enhancing systems to enable team function and continuity of care. Drivers
identified for improving care in these areas included: strong Indigenous
participation in the PHC service; appropriate team structure and function to
support preventive care; meaningful use of data to support quality of care and
CQI; and corporate support functions and structures. CONCLUSION: The framework
should be useful for guiding development and implementation of barrier-driven,
tailored interventions for primary health care service delivery and policy
contexts, and for guiding further research. While specific strategies to improve
the quality of preventive care need to be tailored to local context, these
findings reinforce the requirement for multi-level action across the system. The
framework and findings may be useful for similar purposes in other parts of the
world, with appropriate attention to context in different locations.
PMID- 28705224
TI - More than just a gut feeling: constraint-based genome-scale metabolic models for
predicting functions of human intestinal microbes.
AB - The human gut is colonized with a myriad of microbes, with substantial
interpersonal variation. This complex ecosystem is an integral part of the
gastrointestinal tract and plays a major role in the maintenance of homeostasis.
Its dysfunction has been correlated to a wide array of diseases, but the
understanding of causal mechanisms is hampered by the limited amount of cultured
microbes, poor understanding of phenotypes, and the limited knowledge about
interspecies interactions. Genome-scale metabolic models (GEMs) have been used in
many different fields, ranging from metabolic engineering to the prediction of
interspecies interactions. We provide showcase examples for the application of
GEMs for gut microbes and focus on (i) the prediction of minimal, synthetic, or
defined media; (ii) the prediction of possible functions and phenotypes; and
(iii) the prediction of interspecies interactions. All three applications are key
in understanding the role of individual species in the gut ecosystem as well as
the role of the microbiota as a whole. Using GEMs in the described fashions has
led to designs of minimal growth media, an increased understanding of microbial
phenotypes and their influence on the host immune system, and dietary
interventions to improve human health. Ultimately, an increased understanding of
the gut ecosystem will enable targeted interventions in gut microbial composition
to restore homeostasis and appropriate host-microbe crosstalk.
PMID- 28705225
TI - The impact of social engagement on health-related quality of life and depressive
symptoms in old age - evidence from a multicenter prospective cohort study in
Germany.
AB - BACKGROUND: Thus far, only a few longitudinal studies investigated the impact of
social engagement on health-related quality of life (HRQoL) and depressive
symptoms in old age. Therefore, we aimed to examine the impact of social
engagement on HRQoL and depressive symptoms in late life. METHODS: Individuals
aged 75 years and over at baseline were interviewed every 1.5 years in a
multicenter prospective cohort study in Germany. While HRQoL was quantified by
using the Visual Analogue Scale (EQ VAS) of the EQ-5D instrument, depressive
symptoms was assessed by using the Geriatric Depression Scale (GDS). Individuals
reported the frequency ("never" to "every day") of social engagement (e.g.,
engagement in the church, as a volunteer, in a party, or in a club) in the last
four weeks. Fixed effects regressions were used to estimate the effect of social
engagement on the outcome variables. RESULTS: After adjusting for age, marital
status, functional status and chronic diseases, fixed effects regressions
revealed that the onset of social engagement markedly increased HRQoL and
considerably decreased depressive symptoms in the total sample and in women, but
not men. CONCLUSIONS: Our findings corroborate the relevance of social engagement
for HRQoL and depressive symptoms in old age. Encouraging the individuals to
start, maintain and expand social engagement in late life might help to maintain
and improve HRQoL and decrease depressive symptoms.
PMID- 28705226
TI - Continuous surveillance of a pregnancy clinical guideline: an early experience.
AB - BACKGROUND: To date there is no consensus about the optimal strategy for keeping
clinical guidelines (CGs) up-to-date. The aims of this study were (1) to develop
a continuous surveillance and updating strategy for CGs and (2) to test the
strategy in a specific CG. METHODS: The main steps were as follows: (1)
recruiting members for the CG Updating Working Group, (2) mapping the CG, (3)
identifying new evidence from the CG Updating Working Group, (4) designing and
running restricted literature searches, (5) reviewing drugs and medical devices
alerts, (6) screening and assessing the new evidence, (7) reviewing and, if
necessary, modifying clinical questions and recommendations, and (8) updating the
CG document. RESULTS: The Pregnancy CG Updating Working Group consisted of 29
members, including clinicians, patients and caregivers, and clinical guideline
methodology experts. We selected 69 clinical questions (123 recommendations) from
the "Assistance during pregnancy" section. For the first update cycle (32-month
duration), 9710 references were identified. Of these, 318 were pertinent, 289
were relevant, and 55 were classified as potential key references. For the second
and third update cycles (6-month duration each), 2160 and 2010 references were
retrieved, respectively. The continuous surveillance and updating strategy has
not yet been completely implemented. CONCLUSIONS: Further resources are needed in
updating the CG field, both for implementing updating strategies and for
developing methodological research.
PMID- 28705227
TI - Sensorimotor Learning: Neurocognitive Mechanisms and Individual Differences.
AB - Here we provide an overview of findings and viewpoints on the mechanisms of
sensorimotor learning presented at the 2016 Biomechanics and Neural Control of
Movement (BANCOM) conference in Deer Creek, OH. This field has shown substantial
growth in the past couple of decades. For example it is now well accepted that
neural systems outside of primary motor pathways play a role in learning.
Frontoparietal and anterior cingulate networks contribute to sensorimotor
adaptation, reflecting strategic aspects of exploration and learning. Longer term
training results in functional and morphological changes in primary motor and
somatosensory cortices. Interestingly, re-engagement of strategic processes once
a skill has become well learned may disrupt performance. Efforts to predict
individual differences in learning rate have enhanced our understanding of the
neural, behavioral, and genetic factors underlying skilled human performance.
Access to genomic analyses has dramatically increased over the past several
years. This has enhanced our understanding of cellular processes underlying the
expression of human behavior, including involvement of various neurotransmitters,
receptors, and enzymes. Surprisingly our field has been slow to adopt such
approaches in studying neural control, although this work does require much
larger sample sizes than are typically used to investigate skill learning. We
advocate that individual differences approaches can lead to new insights into
human sensorimotor performance. Moreover, a greater understanding of the factors
underlying the wide range of performance capabilities seen across individuals can
promote personalized medicine and refinement of rehabilitation strategies, which
stand to be more effective than "one size fits all" treatments.
PMID- 28705229
TI - Brugada syndrome in a patient with amyotrophic lateral sclerosis: a case report.
AB - BACKGROUND: Amyotrophic lateral sclerosis is a fatal neuromuscular disorder
characterized by progressive death of the upper and lower motor neurons in the
central nervous system. Patients with this disease die mostly as a result of
respiratory failure; however, owing to prolonged survival through assisted
ventilation, cardiovascular causes are increasingly responsible for mortality. We
report what is to the best of our knowledge the first case of type 2 Brugada
syndrome causing ventricular tachyarrhythmia and cardiac arrest in a patient with
upper limb onset amyotrophic lateral sclerosis. CASE PRESENTATION: A 48-year-old
Caucasian woman with a significant past medical history of papillary thyroid
carcinoma status postresection, pulmonary embolism on anticoagulation, and a
recent diagnosis of right upper limb-onset amyotrophic lateral sclerosis
presented to the emergency department of our hospital with acute on chronic
shortness of breath. On further evaluation, she was found to have hypoxic and
hypercapnic respiratory failure and was placed on bilevel positive airway
pressure ventilation. Her 12-lead electrocardiogram showed sinus rhythm with J
point elevation, saddle-shaped ST segment elevation, predominantly in V1 and V2
with no significant QTc prolongation. No troponin elevation was noted in her
laboratory workup. Because she was unable to protect her airway, a decision was
made to intubate her. After 1 minute of induction with etomidate and
succinylcholine, she went into pulseless ventricular tachycardia and fibrillation
requiring three cycles of cardiopulmonary resuscitation with high-quality chest
compressions, three doses of epinephrine, and a loading dose of amiodarone prior
to return of spontaneous circulation. She was further evaluated by cardiology
services and was diagnosed with type 2 Brugada syndrome, for which she was
started on quinidine. Her respiratory failure and the drugs she received for
intubation likely caused her ventricular tachycardia to occur in conjunction with
an underlying Brugada pattern seen on an electrocardiogram. The results of
evaluation of her genetic panel for Brugada syndrome were negative. She was
subsequently discharged to home in stable condition after a 10-day hospital stay.
CONCLUSIONS: Amyotrophic lateral sclerosis is a progressive neuromuscular
disorder with significant mortality. Respiratory failure is the leading cause of
death, but lately, owing to increased survival associated with early tracheostomy
and positive pressure ventilation, there has been an increasing trend in the
identification of cardiovascular causes of mortality, especially arrhythmias,
that may need periodic electrocardiographic surveillance.
PMID- 28705228
TI - Cleanliness in context: reconciling hygiene with a modern microbial perspective.
AB - The concept of hygiene is rooted in the relationship between cleanliness and the
maintenance of good health. Since the widespread acceptance of the germ theory of
disease, hygiene has become increasingly conflated with sterilization. In
reviewing studies across the hygiene literature (most often hand hygiene), we
found that nearly all studies of hand hygiene utilize bulk reduction in bacterial
load as a proxy for reduced transmission of pathogenic organisms. This treatment
of hygiene may be insufficient in light of recent microbial ecology research,
which has demonstrated that humans have intimate and evolutionarily significant
relationships with a diverse assemblage of microorganisms (our microbiota). The
human skin is home to a diverse and specific community of microorganisms, which
include members that exist across the ecological spectrum from pathogen through
commensal to mutualist. Most evidence suggests that the skin microbiota is likely
of direct benefit to the host and only rarely exhibits pathogenicity. This
complex ecological context suggests that the conception of hygiene as a
unilateral reduction or removal of microbes has outlived its usefulness. As such,
we suggest the explicit definition of hygiene as "those actions and practices
that reduce the spread or transmission of pathogenic microorganisms, and thus
reduce the incidence of disease."
PMID- 28705230
TI - Changes in hepatitis B virus antibody titers over time among children: a single
center study from 2012 to 2015 in an urban of South Korea.
AB - BACKGROUND: Hepatitis B virus (HBV) infection is the most common cause of liver
disease in endemic areas such as South Korea. After HBV vaccination, hepatitis B
surface antibody (HBsAb) titers gradually decrease. Trends in HBsAb titers have
not been evaluated among children in South Korea over the past decade. METHODS:
We screened 6155 patients (aged 7 months to 17 years) who underwent HBV
antigen/antibody testing at Chung-Ang University Hospital from May 2012 to April
2015. Titer criteria were defined as follows: positive, titer >=100 IU/L; weakly
positive, titer 10-99 IU/L; and negative, titer <10 IU/L. We also compared titers
before and 1 month after a single booster vaccination. RESULTS: Of the 5655
patients included, 3016 were male and 5 (0.09%) tested positive for HBV surface
antigen. A marked reduction in antibody titer was observed until 4 years of age.
Thereafter, the titers showed fluctuating decreases. HBsAb titers reached their
lowest levels by 14 years of age. After 7 years of age, 50% of patients tested
negative for HBsAb. Simple linear analysis showed that the titer reached levels
of <10 IU/L and zero at 12.9 and 13.4 years of age, respectively. 1 month after a
single booster vaccination was administered to those who were HBsAb-negative (n =
72), 69 children (96%) had developed antibodies while 3 (4%) remained HBsAb
negative. CONCLUSIONS: In conclusion, the continuous reduction in HBsAb titers
over time and in each age group was confirmed. The titer level was shown
significant decline until age 4. More than half of the sample had negative titers
after age 7 years. After booster vaccination, most of child significantly
increase titer level.
PMID- 28705231
TI - Metabolic syndrome and its components in Polish women of childbearing age: a
nationwide study.
AB - BACKGROUND: Abnormal body mass and related metabolic disorders may affect female
reproductive health. The purpose of the study was to determine the prevalence of
underweight, overweight, obesity, lipid and glucose metabolism disorders,
hypertension, and metabolic syndrome, among Polish women of childbearing age.
METHODS: One thousand five hundred eighty-eight non-pregnant Polish women of
childbearing age (20-49 years) who participated in the Multi-Centre National
Population Health Examination Survey (WOBASZ II study) in 2013-2014, were
assigned to 3 age groups: 20-29 years (n = 403), 30-39 years (n = 600) and 40-49
years (n = 585). Measurements of weight, height, waist circumference, blood
pressure, blood lipids, and blood glucose were taken. For statistical analysis,
the Kruskal-Wallis, Chi-Square, and Cohran-Armitage tests were used. RESULTS: Of
the participants, 4.3% were determined to be underweight, 25.2% were overweight,
15% were obese, and 53.1% had abdominal obesity. With age, the prevalence of both
excessive body mass and abdominal obesity tended to increase, and that of
underweight to decrease. Frequency of hypercholesterolemia and
hypertriglyceridemia found in the whole group were 50% and 12.6% respectively,
and also tended to rise with age. Low serum HDL-cholesterol (high density
lipoprotein cholesterol) levels were found in 15.1% of the participants.
Prevalence of impaired fasting glucose in the whole group was 8.2% and tended to
increase with age. Diabetes was found in 1.2% of the participants and its
prevalence also tended to rise with age, at the borderline of significance.
Frequency of arterial hypertension and metabolic syndrome in the whole group was
15.7% and 14.1% respectively and both tended to increase with age. CONCLUSIONS:
Overweight and obesity, especially of abdominal type, and the related metabolic
abnormalities are common in Polish women of childbearing age. Their prevalence
tends to increase with age. Underweight is relatively common in the youngest age
group.
PMID- 28705232
TI - Hypoxia-inducible factor-2alpha promotes tumor progression and has crosstalk with
Wnt/beta-catenin signaling in pancreatic cancer.
AB - BACKGROUND: Pancreatic cancer is a devastating disease that is characterized by
persistent hypoxia. The roles of hypoxia-inducible factor-2alpha (hif-2alpha) are
different to those of hif-1alpha, although both are critical for tumor cells to
adapt to the hypoxic microenvironment. However, unlike the well-studied hif
1alpha, the role of hif-2alpha in tumors, including pancreatic cancer, is poorly
understood. METHODS: Herein, we used a mutated hif-2alpha (A530T) to figure out
the problem that wild-type hif-2alpha is quickly degraded which limits the study
of its function. Using several cell lines, mouse models, and human tissues, we
obtained a general picture of hif-2alpha in pancreatic cancer progression.
RESULTS: Functional assays revealed that hif-2alpha promotes epithelial-to
mesenchymal transition, enhances tumor proliferation and invasion, increases
stemness, facilitates angiogenesis, and up-regulates aerobic glycolysis. We
identified an interaction between hif-2alpha and beta-catenin, and found that hif
2alpha/beta-catenin complex formation increased the activity of beta-catenin and
the protein stability of hif-2alpha. In vivo study confirmed the pro-oncogenic
role of hif-2alpha, whose expression correlated with those of E-cadherin,
vimentin, Ki-67, and CD31, but not hif-1alpha. A human tissue study showed that
hif-2alpha was associated with lymph node metastasis, pathological grade, stroma
abundance, vascularization and patient survival. High expression of hif-2alpha
was also identified as an independent indicator of poor prognosis in patients
with pancreatic cancer. CONCLUSIONS: Our systematic study revealed the roles of
hif-2alpha in pancreatic cancer, and may provide a novel target for this highly
malignant disease.
PMID- 28705233
TI - Erratum to: Detection of Schistosoma Antibodies and exploration of associated
factors among local residents around Inlay Lake, Southern Shan State, Myanmar.
PMID- 28705234
TI - In silico characterization of cell-cell interactions using a cellular automata
model of cell culture.
AB - BACKGROUND: Cell proliferation is a key characteristic of eukaryotic cells.
During cell proliferation, cells interact with each other. In this study, we
developed a cellular automata model to estimate cell-cell interactions using
experimentally obtained images of cultured cells. RESULTS: We used four types of
cells; HeLa cells, human osteosarcoma (HOS) cells, rat mesenchymal stem cells
(MSCs), and rat smooth muscle A7r5 cells. These cells were cultured and stained
daily. The obtained cell images were binarized and clipped into squares
containing about 104 cells. These cells showed characteristic cell proliferation
patterns. The growth curves of these cells were generated from the cell
proliferation images and we determined the doubling time of these cells from the
growth curves. We developed a simple cellular automata system with an easily
accessible graphical user interface. This system has five variable parameters,
namely, initial cell number, doubling time, motility, cell-cell adhesion, and
cell-cell contact inhibition (of proliferation). Within these parameters, we
obtained initial cell numbers and doubling times experimentally. We set the
motility at a constant value because the effect of the parameter for our
simulation was restricted. Therefore, we simulated cell proliferation behavior
with cell-cell adhesion and cell-cell contact inhibition as variables. By
comparing growth curves and proliferation cell images, we succeeded in
determining the cell-cell interaction properties of each cell. Simulated HeLa and
HOS cells exhibited low cell-cell adhesion and weak cell-cell contact inhibition.
Simulated MSCs exhibited high cell-cell adhesion and positive cell-cell contact
inhibition. Simulated A7r5 cells exhibited low cell-cell adhesion and strong cell
cell contact inhibition. These simulated results correlated with the experimental
growth curves and proliferation images. CONCLUSIONS: Our simulation approach is
an easy method for evaluating the cell-cell interaction properties of cells.
PMID- 28705235
TI - Burden and associated factors of anemia among pregnant women attending antenatal
care in southern Ethiopia: cross sectional study.
AB - BACKGROUND: Anemia is a condition in which the number of red blood cells or their
oxygen-carrying capacity is insufficient to meet physiologic needs, which varies
by age, sex, altitude, smoking, and pregnancy status. The study aim is to
determine the prevalence and factors associated with anemia among pregnant women
attending a hospital in southern Ethiopia using a structured interview
administered questionnaire. METHODS: Facility-based cross-sectional study was
conducted from March 01-April 30 2015 at Butajira General Hospital, Ethiopia. A
total of 217 women responded to the questionnaire and provided blood and stool
samples for analysis. Data were analyzed using Statistical packages for social
sciences version 20 for windows. RESULT AND CONCLUSIONS: The overall burden of
anemia in this study was 27.6%. Residence, ANC follow up, history of excess
menstrual bleeding and interpregnancy interval were statistically associated with
anemia among the pregnant women. Therefore, working in the identified gaps could
reduce the current burden of anemia among pregnant women in the study area.
PMID- 28705236
TI - Youth drinking and acute harm: a perspective from the UK on effective engagement
opportunities.
AB - ?: Youth drinking is linked with acute harms and Emergency Departments (ED) are
places where some of these harms become apparent. This commentary argues that
there is a clear case for routinely monitoring alcohol harm at ED and delivering
brief interventions to engage with people at a time when they may be more likely
to consider lifestyle behaviour change. Based on insights from the UK, it is
suggested that young people may not always easily be engaged through messages
that focus directly on alcohol harm, and efforts to engage them through issues
that matter to them (such as sexual harassment) might add to the effectiveness.
PMID- 28705237
TI - ddRADseq reveals determinants for temperature-dependent sex reversal in Nile
tilapia on LG23.
AB - BACKGROUND: In Nile tilapia sex determination is governed by a male heterogametic
system XX/XY either on LG1 or LG23. The latter carries a Y-specific duplicate of
the amh gene, which is a testis-determining factor. Allelic variants in the amh
gene demonstrated to be major triggers for autosomal and temperature-dependent
sex reversal. Further, QTL on LG23 and LG20 show a temperature-responsiveness
with influence on the phenotypic sex relative to the sex chromosomes. Here we
present a ddRADseq based approach to identify genomic regions that show unusual
large differentiation in terms of fixation index (FST) between temperature
treated pseudomales and non-masculinized females using a comparative genome-scan.
Genome-wide associations were identified for the temperature-dependent sex using
a genetically all-female population devoid of amh-DeltaY. RESULTS: Twenty-two
thousand three hundred ninety-two SNPs were interrogated for the comparison of
temperature-treated pseudomales and females, which revealed the largest
differentiation on LG23. Outlier FST-values (0.35-0.44) were determined for six
SNPs in the genomic interval (9,190,077-11,065,693) harbouring the amh gene
(9,602,693-9,605,808), exceeding the genome-wide low FST of 0.013. Association
analysis with a set of 9104 selected SNPs confirmed that the same genomic region
on LG23 exerts a significant effect on the temperature-dependent sex.
CONCLUSIONS: This study highlights the role of LG23 in sex determination,
harbouring major determinants for temperature-dependent sex reversal in Nile
tilapia. Furthermore FST outlier detection proves a powerful tool for detection
of sex-determining regions in fish genomes.
PMID- 28705238
TI - Interleukin-3 enhances the migration of human mesenchymal stem cells by
regulating expression of CXCR4.
AB - BACKGROUND: Mesenchymal stem cells (MSCs) represent an important source for cell
therapy in regenerative medicine. MSCs have shown promising results for repair of
damaged tissues in various degenerative diseases in animal models and also in
human clinical trials. However, little is known about the factors that could
enhance the migration and tissue-specific engraftment of exogenously infused MSCs
for successful regenerative cell therapy. Previously, we have reported that
interleukin-3 (IL-3) prevents bone and cartilage damage in animal models of
rheumatoid arthritis and osteoarthritis. Also, IL-3 promotes the differentiation
of human MSCs into functional osteoblasts and increases their in-vivo bone
regenerative potential in immunocompromised mice. However, the role of IL-3 in
migration of MSCs is not yet known. In the present study, we investigated the
role of IL-3 in migration of human MSCs under both in-vitro and in-vivo
conditions. METHODS: MSCs isolated from human bone marrow, adipose and gingival
tissues were used for in-vitro cell migration, motility and wound healing assays
in the presence or absence of IL-3. The effect of IL-3 preconditioning on
expression of chemokine receptors and integrins was examined by flow cytometry
and real-time PCR. The in-vivo migration of IL-3-preconditioned MSCs was
investigated using a subcutaneous matrigel-releasing stromal cell-derived factor
1 alpha (SDF-1alpha) model in immunocompromised mice. RESULTS: We observed that
human MSCs isolated from all three sources express IL-3 receptor-alpha (IL
3Ralpha) both at gene and protein levels. IL-3 significantly enhances in-vitro
migration, motility and wound healing abilities of MSCs. Moreover, IL-3
preconditioning upregulates expression of chemokine (C-X-C motif) receptor 4
(CXCR4) on MSCs, which leads to increased migration of cells towards SDF-1alpha.
Furthermore, CXCR4 antagonist AMD3100 decreases the migration of IL-3-treated
MSCs towards SDF-1alpha. Importantly, IL-3 also induces in-vivo migration of MSCs
towards subcutaneously implanted matrigel-releasing-SDF-1alpha in
immunocompromised mice. CONCLUSIONS: The present study demonstrates for the first
time that IL-3 has an important role in enhancing the migration of human MSCs
through regulation of the CXCR4/SDF-1alpha axis. These findings suggest a
potential role of IL-3 in improving the efficacy of MSCs in regenerative cell
therapy.
PMID- 28705239
TI - NAP: The Network Analysis Profiler, a web tool for easier topological analysis
and comparison of medium-scale biological networks.
AB - OBJECTIVE: Nowadays, due to the technological advances of high-throughput
techniques, Systems Biology has seen a tremendous growth of data generation. With
network analysis, looking at biological systems at a higher level in order to
better understand a system, its topology and the relationships between its
components is of a great importance. Gene expression, signal transduction,
protein/chemical interactions, biomedical literature co-occurrences, are few of
the examples captured in biological network representations where nodes represent
certain bioentities and edges represent the connections between them. Today, many
tools for network visualization and analysis are available. Nevertheless, most of
them are standalone applications that often (i) burden users with computing and
calculation time depending on the network's size and (ii) focus on handling,
editing and exploring a network interactively. While such functionality is of
great importance, limited efforts have been made towards the comparison of the
topological analysis of multiple networks. RESULTS: Network Analysis Provider
(NAP) is a comprehensive web tool to automate network profiling and intra/inter
network topology comparison. It is designed to bridge the gap between network
analysis, statistics, graph theory and partially visualization in a user-friendly
way. It is freely available and aims to become a very appealing tool for the
broader community. It hosts a great plethora of topological analysis methods such
as node and edge rankings. Few of its powerful characteristics are: its ability
to enable easy profile comparisons across multiple networks, find their
intersection and provide users with simplified, high quality plots of any of the
offered topological characteristics against any other within the same network. It
is written in R and Shiny, it is based on the igraph library and it is able to
handle medium-scale weighted/unweighted, directed/undirected and bipartite
graphs. NAP is available at http://bioinformatics.med.uoc.gr/NAP .
PMID- 28705240
TI - A rule-based electronic phenotyping algorithm for detecting clinically relevant
cardiovascular disease cases.
AB - BACKGROUND: The implementation of electronic medical records (EMR) is becoming
increasingly common. Error and data loss reduction, patient-care efficiency
increase, decision-making assistance and facilitation of event surveillance, are
some of the many processes that EMRs help improve. In addition, they show a lot
of promise in terms of data collection to facilitate observational
epidemiological studies and their use for this purpose has increased
significantly over the recent years. Even though the quantity and availability of
the data are clearly improved thanks to EMRs, still, the problem of the quality
of the data remains. This is especially important when attempting to determine if
an event has actually occurred or not. We sought to assess the sensitivity,
specificity, and agreement level of a codes-based algorithm for the detection of
clinically relevant cardiovascular (CaVD) and cerebrovascular (CeVD) disease
cases, using data from EMRs. METHODS: Three family physicians from the research
group selected clinically relevant CaVD and CeVD terms from the international
classification of primary care, Second Edition (ICPC-2), the ICD 10 version 2015
and SNOMED-CT 2015 Edition. These terms included both signs, symptoms, diagnoses
and procedures associated with CaVD and CeVD. Terms not related to symptoms,
signs, diagnoses or procedures of CaVD or CeVD and also those describing
incidental findings without clinical relevance were excluded. The algorithm
yielded a positive result if the patient had at least one of the selected terms
in their medical records, as long as it was not recorded as an error. Else, if no
terms were found, the patient was classified as negative. This algorithm was
applied to a randomly selected sample of the active patients within the
hospital's HMO by 1/1/2005 that were 40-79 years old, had at least one year of
seniority in the HMO and at least one clinical encounter. Thus, patients were
classified into four groups: (1) Negative patients (2) Patients with CaVD but
without CeVD; (3) Patients with CeVD but without disease CaVD; (4) Patients with
both diseases. To facilitate the validation process, a stratified sample was
taken so that each of the groups represented approximately 25% of the sample.
Manual chart review was used as the gold standard for assessing the algorithm's
performance. One-third of the patients were assigned randomly to each reviewer
(Cohen's kappa 0.91). Both coded and un-coded (free text) sections of the EMR
were reviewed. This was done from the first present clinical note in the patients
chart to the last one registered prior to 1/1/2005. RESULTS: The performance of
the algorithm was compared against manual chart review. It yielded high
sensitivity (0.99, 95% CI 0.938-0.9971) and acceptable specificity (0.86, 95% CI
0.818-0.895) for detecting cases of CaVD and CeVD combined. A qualitative
analysis of the false positives and false negatives was performed. CONCLUSIONS:
We developed a simple algorithm, using only standardized and non-standardized
coded terms within an EMR that can properly detect clinically relevant events and
symptoms of CaVD and CeVD. We believe that combining it with an analysis of the
free text using an NLP approach would yield even better results.
PMID- 28705241
TI - Demand and willingness-to-pay for bed nets in Tanzania: results from a choice
experiment.
AB - BACKGROUND: Universal coverage campaigns for long-lasting insecticide-treated
nets do not always reach the goal of one net for every two household members, and
even when ownership of at least one net per household is high, many households
may not own enough nets. The retail market provides these households options for
replacing or increasing the number of nets they own with products that best fit
their needs since a variety of net shapes, sizes, and colours are available.
Hence, it is important to understand the factors affecting private net demand.
This study explores private demand for nets in Tanzania using a discrete choice
experiment. The experiment provides participants the option to buy nets with
their own money, and thus should prove more accurate than a hypothetical survey
of net preferences. RESULTS: Nearly 800 participants sampled in two regions
showed an overall strong demand for nets, with 40% choosing to buy a net across
all seven combinations of net prices and characteristics such as size, shape, and
insecticide treatment. Only 8% of all participants chose not to buy a single net.
A key factor influencing demand was whether a participant's household currently
owned sufficient nets for all members, with rural participants showing lower net
coverage and greater demand than urban participants. Both poor and less poor
households showed strong evidence of making purchase decisions based on more than
price alone. Mean willingness-to-pay values for a net started at US$1.10 and grew
by US$0.50-1.40 for various attributes such as rectangular shape, large size, and
insecticide treatment. The impact of price on demand was negative but small, with
elasticity values between -0.25 and -0.45. CONCLUSIONS: The results suggest that
private demand for nets in Tanzania could potentially supplement future coverage
campaigns. Net manufacturers and retailers should advertise and promote
consumers' preferred net attributes to improve sales and further expand net
access and coverage. To overcome household liquidity concerns and best replicate
the experiment results, policy makers should consider making credit available for
interested buyers.
PMID- 28705242
TI - Non-communicable diseases and related risk behaviors among men and women living
with HIV in Cambodia: findings from a cross-sectional study.
AB - BACKGROUND: There is a growing concern for an increasing burden of non
communicable diseases (NCDs) in people living with HIV. This concern is evident
especially in developing countries where dietary and lifestyle risk factors
associated with NCDs are becoming more prominent. This study explored the
prevalence of diabetes mellitus, hypertension, and hyperlipidemia and related
risk factors in men and women living with HIV in Cambodia. METHODS: This cross
sectional study was conducted among 510 adult people living with HIV randomly
selected from one city and four provinces in Cambodia. A structured questionnaire
was used to collect data on socio-demographic characteristics, health behaviors,
medical history, and antiretroviral therapy (ART). Anthropometric and biological
measurements were performed. Descriptive statistics were used to calculate
proportions and means of the measured variables. An independent Student's t-test
was used for continuous variables. Chi square test or Fisher's exact test was
used for categorical variables to explore gender differences. RESULTS: Prevalence
of diabetes mellitus, hypertension, and hyperlipidemia was 9.4, 15.1, and 33.7%,
respectively. The prevalence of hyperlipidemia was significantly higher among men
compared to women. Mean systolic and diastolic blood pressures were also
significantly higher among men. Regarding risk factors, 17.3% of participants
were overweight, and 4.1% were obese. Tobacco and alcohol use was common,
particularly among men. Fruit and vegetable consumption was considerably low
among both men and women. Physical activity levels were also low. About 40% of
participants reported having a job that involved mostly sitting or standing;
46.3% reported engaging in moderate activities; and 11.8% reported engaging in
vigorous activities during leisure time. A significantly higher proportion of men
compared to women engaged in vigorous activities both at work and during leisure
time. CONCLUSIONS: The prevalence of diabetes mellitus, hypertension, and
hyperlipidemia among men and women living with HIV in Cambodia is considerably
high. Related risk factors were also common. Given the comorbidity of NCDs and
HIV, policy and programmatic interventions are required, including integration of
NCD screening into HIV programs. Distinctions in the levels of diseases and in
health behaviors between men and women suggest that interventions need to be
tailor-made and gender-specific, targeting their respective diseases and
behaviors.
PMID- 28705243
TI - Trends in treatment with antipsychotic medication in relation to national
directives, in people with dementia - a review of the Swedish context.
AB - BACKGROUND: The aim of this study was to explore trends in treatment with
antipsychotic medication in Swedish dementia care in nursing homes as reported in
the most recent empirical studies on the topic, and to relate these trends to
directives from the national authorities. METHODS: The study included two scoping
review studies based on searches of electronic databases as well as the Swedish
directives in the field. RESULTS: During the past decade, directives have been
developed for antipsychotic medication in Sweden. These directives were generic
at first, but have become increasingly specific and restrictive with time. The
scoping review showed that treatment with antipsychotic drugs varied between 6%
and 38%, and was higher in younger older persons and in those with moderate
cognitive impairment and living in nursing homes for people with dementia. A
decreasing trend in antipsychotic use has been seen over the last 15 years.
CONCLUSIONS: Directives from the authorities in Sweden may have had an impact on
treatment with antipsychotic medication for people with dementia. Treatment with
antipsychotic medication has decreased, while treatment with combinations of
psychotropic medications is common. National directives may possibly be even more
effective, if applied in combination with systematic follow-ups.
PMID- 28705244
TI - Smoking cessation in severe mental ill health: what works? an updated systematic
review and meta-analysis.
AB - BACKGROUND: People with severe mental ill health are more likely to smoke than
those in the general population. It is therefore important that effective smoking
cessation strategies are used to help people with severe mental ill health to
stop smoking. This study aims to assess the effectiveness and cost
effectiveness of smoking cessation and reduction strategies in adults with severe
mental ill health in both inpatient and outpatient settings. METHODS: This is an
update of a previous systematic review. Electronic databases were searched during
September 2016 for randomised controlled trials comparing smoking cessation
interventions to each other, usual care, or placebo. Data was extracted on
biochemically-verified, self-reported smoking cessation (primary outcome), as
well as on smoking reduction, body weight, psychiatric symptom, and adverse
events (secondary outcomes). RESULTS: We included 26 trials of pharmacological
and/or behavioural interventions. Eight trials comparing bupropion to placebo
were pooled showing that bupropion improved quit rates significantly in the
medium and long term but not the short term (short term RR = 6.42 95% CI 0.82
50.07; medium term RR = 2.93 95% CI 1.61-5.34; long term RR = 3.04 95% CI 1.10
8.42). Five trials comparing varenicline to placebo showed that that the addition
of varenicline improved quit rates significantly in the medium term (RR = 4.13
95% CI 1.36-12.53). The results from five trials of specialised smoking cessation
programmes were pooled and showed no evidence of benefit in the medium (RR = 1.32
95% CI 0.85-2.06) or long term (RR = 1.33 95% CI 0.85-2.08). There was
insufficient data to allowing pooling for all time points for varenicline and
trials of specialist smoking cessation programmes. Trials suggest few adverse
events although safety data were not always reported. Only one pilot study
reported cost effectiveness data. CONCLUSIONS: Bupropion and varenicline, which
have been shown to be effective in the general population, also work for people
with severe mental ill health and their use in patients with stable psychiatric
conditions. Despite good evidence for the effectiveness of smoking cessation
interventions for people with severe mental ill health, the percentage of people
with severe mental ill health who smoke remains higher than that for the general
population.
PMID- 28705245
TI - Abscisic acid induces a transient shift in signaling that enhances NF-kappaB
mediated parasite killing in the midgut of Anopheles stephensi without reducing
lifespan or fecundity.
AB - BACKGROUND: Abscisic acid (ABA) is naturally present in mammalian blood and
circulating levels can be increased by oral supplementation. We showed previously
that oral ABA supplementation in a mouse model of Plasmodium yoelii 17XNL
infection reduced parasitemia and gametocytemia, spleen and liver pathology, and
parasite transmission to the mosquito Anopheles stephensi fed on these mice.
Treatment of cultured Plasmodium falciparum with ABA at levels detected in our
model had no effects on asexual growth or gametocyte formation in vitro. However,
ABA treatment of cultured P. falciparum immediately prior to mosquito feeding
significantly reduced oocyst development in A. stephensi via ABA-dependent
synthesis of nitric oxide (NO) in the mosquito midgut. RESULTS: Here we describe
the mechanisms of effects of ABA on mosquito physiology, which are dependent on
phosphorylation of TGF-beta-activated kinase 1 (TAK1) and associated with changes
in homeostatic gene expression and activity of kinases that are central to
metabolic regulation in the midgut epithelium. Collectively, the timing of these
effects suggests a transient physiological shift that enhances NF-kappaB
dependent innate immunity without significantly altering mosquito lifespan or
fecundity. CONCLUSIONS: ABA is a highly conserved regulator of immune and
metabolic homeostasis within the malaria vector A. stephensi with potential as a
transmission-blocking supplemental treatment.
PMID- 28705246
TI - Effects of additional team-based learning on students' clinical reasoning skills:
a pilot study.
AB - BACKGROUND: In the field of Neurology good clinical reasoning skills are
essential for successful diagnosing and treatment. Team-based learning (TBL), an
active learning and small group instructional strategy, is a promising method for
fostering these skills. The aim of this pilot study was to examine the effects of
a supplementary TBL-class on students' clinical decision-making skills. METHODS:
Fourth- and fifth-year medical students participated in this pilot study (static
group comparison design). The non-treatment group (n = 15) did not receive any
additional training beyond regular teaching in the neurology course. The
treatment group (n = 11) took part in a supplementary TBL-class optimized for
teaching clinical reasoning in addition to the regular teaching in the neurology
course. Clinical decision making skills were assessed using a key-feature problem
examination. Factual and conceptual knowledge was assessed by a multiple-choice
question examination. RESULTS: The TBL-group performed significantly better than
the non-TBL-group (p = 0.026) in the key-feature problem examination. No
significant differences between the results of the multiple-choice question
examination of both groups were found. CONCLUSIONS: In this pilot study
participants of a supplementary TBL-class significantly improved clinical
decision-making skills, indicating that TBL may be an appropriate method for
teaching clinical decision making in neurology. Further research is needed for
replication in larger groups and other clinical fields.
PMID- 28705247
TI - Detecting impaired myocardial relaxation in sepsis with a novel tissue Doppler
parameter (septal e'/s').
AB - BACKGROUND: Left ventricular diastolic dysfunction is associated with mortality
outcomes in severe sepsis and septic shock. There are ongoing issues with
diagnosing diastolic dysfunction in this cohort, partly owing to the poor
applicability of traditional parameters in the hyperdynamic circulation. In this
feasibility study, we sought to assess the utility of a novel parameter (septal
e'/s') to identify diastolic dysfunction in patients with severe sepsis and
septic shock who had normal systolic function against the 2016 American Society
Echocardiography and European Association of Cardiovascular Imaging (ASE/EACI)
guidelines on diastolic dysfunction. METHODS: In this prospective observational
pilot study, patients identified as having severe sepsis and septic shock
underwent transthoracic echocardiography on day 1 and day 3 of their intensive
care unit admission. In patients with normal systolic function, septal e'/s' was
calculated using the peak modal velocity of the s' compared with the e' from the
septal annulus tissue Doppler imaging and compared with their diastolic grade
according to the 2016 ASE/EACI guidelines on diastolic dysfunction. RESULTS: On
day 1 of admission, 44 of 62 patients with severe sepsis and septic shock had
normal systolic function. There was a strong association of those with diastolic
dysfunction having a reduced septal e'/s' compared with patients with normal
diastolic function (AUC 0.91). A similar relationship was seen with patients who
had indeterminate diastolic dysfunction. On day 3, 37 patients had normal
systolic function. Again, there was a strong association of those with diastolic
dysfunction and a reduced septal e'/s' (AUC 0.95). CONCLUSIONS: A reduction in
septal e'/s' may indicate diastolic dysfunction in patients with severe sepsis
and septic shock who have normal systolic function. As opposed to limited
traditional measures of diastolic dysfunction, it is applicable in those with
hyperdynamic systolic function.
PMID- 28705248
TI - Prevention of feline leishmaniosis with an imidacloprid 10%/flumethrin 4.5%
polymer matrix collar.
AB - BACKGROUND: Leishmaniosis caused by Leishmania infantum is one of the most
important vector-borne diseases affecting animals and humans worldwide. Dogs are
considered main reservoirs of the zoonotic forms, though in the last years the
role of cats as reservoirs has been increasingly investigated. Feline
leishmaniosis (FeL) occurs in endemic areas and no specific preventive measures
have been investigated so far. In this study the efficacy of a 10%
imidacloprid/4.5% flumethrin polymer matrix collar, licensed for tick and flea
prevention, has been assessed against FeL in a longitudinal study on 204
privately owned cats from the Aeolian islands (Sicily), an area highly endemic
for the disease. From March to May 2015 [Study Day 0 (SD 0)], cats negative for
FeL were collared (G1, n = 104) or left untreated (G2, n = 100). Diagnosis
consisted of serology and qPCR on blood and conjunctival swabs, which were
collected at baseline (SD 0) and at the end of the study (SD 360). Interim
clinical examinations were performed on SD 210 (when collars were replaced in G1)
and SD 270. RESULTS: Of the 159 cats which completed the study, 5 in G1 and 20 in
G2 were positive for L. infantum infection, in at least one of the diagnostic
tests leading to a yearly crude incidence of 6.3% and 25.0% in G1 and G2,
respectively (P = 0.0026). This translates into an efficacy of the collar of
75.0% in preventing feline Leishmania infection. The collar was generally well
tolerated with no systemic adverse reactions and few local skin reactions were
observed in the application area in four out of 104 treated cats (3.8%).
CONCLUSIONS: The 10% imidacloprid/4.5% flumethrin collar significantly reduced
the risk of L. infantum infection in cats. To our knowledge, this is the first
study in which a preventative strategy against feline Leishmania infection is
assessed under natural conditions. These findings close a gap in veterinary
medicine, in that they confirm this collar as a tool in reducing the risk of
Leishmania infection in cats. Such a preventative tool could contribute to the
reduction of the risk of the disease in animal and in human populations when
included in integrated leishmaniosis control programmes.
PMID- 28705249
TI - Vector control with driving Y chromosomes: modelling the evolution of resistance.
AB - BACKGROUND: The introduction of new malaria control interventions has often led
to the evolution of resistance, both of the parasite to new drugs and of the
mosquito vector to new insecticides, compromising the efficacy of the
interventions. Recent progress in molecular and population biology raises the
possibility of new genetic-based interventions, and the potential for resistance
to evolve against these should be considered. Here, population modelling is used
to determine the main factors affecting the likelihood that resistance will
evolve against a synthetic, nuclease-based driving Y chromosome that produces a
male-biased sex ratio. METHODS: A combination of deterministic differential
equation models and stochastic analyses involving branching processes and
Gillespie simulations is utilized to assess the probability that resistance
evolves against a driving Y that otherwise is strong enough to eliminate the
target population. The model considers resistance due to changes at the target
site such that they are no longer cleaved by the nuclease, and due to trans
acting autosomal suppressor alleles. RESULTS: The probability that resistance
evolves increases with the mutation rate and the intrinsic rate of increase of
the population, and decreases with the strength of drive and any pleiotropic
fitness costs of the resistant allele. In seasonally varying environments, the
time of release can also affect the probability of resistance evolving. Trans
acting suppressor alleles are more likely to suffer stochastic loss at low
frequencies than target site resistant alleles. CONCLUSIONS: As with any other
intervention, there is a risk that resistance will evolve to new genetic
approaches to vector control, and steps should be taken to minimize this
probability. Two design features that should help in this regard are to reduce
the rate at which resistant mutations arise, and to target sequences such that if
they do arise, they impose a significant fitness cost on the mosquito.
PMID- 28705250
TI - Effect of manufacturing and experimental conditions on the mechanical and surface
properties of silicone elastomer scaffolds used in endothelial mechanobiological
studies.
AB - BACKGROUND: Mechanobiological studies allow the characterization of cell response
to mechanical stresses. Cells need to be supported by a material with properties
similar to the physiological environment. Silicone elastomers have been used to
produce various in vitro scaffolds of different geometries for endothelial cell
studies given its relevant mechanical, optical and surface properties. However,
obtaining defined and repeatable properties is a challenge as depending on the
different manufacturing and processing steps, mechanical and surface properties
may vary significantly between research groups. METHODS: The impact of different
manufacturing and processing methods on the mechanical and surface properties was
assessed by measuring the Young's modulus and the contact angle. Silicone samples
were produced using different curing temperatures and processed with different
sterilization techniques and hydrophilization conditions. RESULTS: Different
curing temperatures were used to obtain materials of different stiffness with a
chosen silicone elastomer, i.e. Sylgard 184(r). Sterilization by boiling had a
tendency to stiffen samples cured at lower temperatures whereas UV and ethanol
did not alter the material properties. Hydrophilization using sulphuric acid
allowed to decrease surface hydrophobicity, however this effect was lost over
time as hydrophobic recovery occurred. Extended contact with water maintained
decreased hydrophobicity up to 7 days. Mechanobiological studies require complete
cell coverage of the scaffolds used prior to mechanical stresses exposure.
Different concentrations of fibronectin and collagen were used to coat the
scaffolds and cell seeding density was varied to optimize cell coverage.
CONCLUSION: This study highlights the potential bias introduced by manufacturing
and processing conditions needed in the preparation of scaffolds used in
mechanobiological studies involving endothelial cells. As manufacturing,
processing and cell culture conditions are known to influence cell adhesion and
function, they should be more thoroughly assessed by research groups that perform
such mechanobiological studies using silicone.
PMID- 28705251
TI - Erratum to: Shock induced endotheliopathy (SHINE) in acute critical illness - a
unifying pathophysiologic mechanism.
PMID- 28705252
TI - Efficacy of prospective pharmacogenetic testing in the treatment of major
depressive disorder: results of a randomized, double-blind clinical trial.
AB - BACKGROUND: A 12-week, double-blind, parallel, multi-center randomized controlled
trial in 316 adult patients with major depressive disorder (MDD) was conducted to
evaluate the effectiveness of pharmacogenetic (PGx) testing for drug therapy
guidance. METHODS: Patients with a CGI-S >= 4 and requiring antidepressant
medication de novo or changes in their medication regime were recruited at 18
Spanish public hospitals, genotyped with a commercial PGx panel
(Neuropharmagen(r)), and randomized to PGx-guided treatment (n = 155) or
treatment as usual (TAU, control group, n = 161), using a computer-generated
random list that locked or unlocked psychiatrist access to the results of the PGx
panel depending on group allocation. The primary endpoint was the proportion of
patients achieving a sustained response (Patient Global Impression of
Improvement, PGI-I <= 2) within the 12-week follow-up. Patients and interviewers
collecting the PGI-I ratings were blinded to group allocation. Between-group
differences were evaluated using chi2-test or t-test, as per data type. RESULTS:
Two hundred eighty patients were available for analysis at the end of the 12-week
follow-up (PGx n = 136, TAU n = 144). A difference in sustained response within
the study period (primary outcome) was not observed (38.5% vs 34.4%, p = 0.4735;
OR = 1.19 [95%CI 0.74-1.92]), but the PGx-guided treatment group had a higher
responder rate compared to TAU at 12 weeks (47.8% vs 36.1%, p = 0.0476; OR = 1.62
[95%CI 1.00-2.61]), and this difference increased after removing subjects in the
PGx-guided group when clinicians explicitly reported not to follow the test
recommendations (51.3% vs 36.1%, p = 0.0135; OR = 1.86 [95%CI 1.13-3.05]).
Effects were more consistent in patients with 1-3 failed drug trials. In subjects
reporting side effects burden at baseline, odds of achieving a better
tolerability (Frequency, Intensity and Burden of Side Effects Rating Burden
subscore <=2) were higher in the PGx-guided group than in controls at 6 weeks and
maintained at 12 weeks (68.5% vs 51.4%, p = 0.0260; OR = 2.06 [95%CI 1.09-3.89]).
CONCLUSIONS: PGx-guided treatment resulted in significant improvement of MDD
patient's response at 12 weeks, dependent on the number of previously failed
medication trials, but not on sustained response during the study period. Burden
of side effects was also significantly reduced. TRIAL REGISTRATION: European
Clinical Trials Database 2013-002228-18 , registration date September 16, 2013;
ClinicalTrials.gov NCT02529462 , retrospectively registered: August 19, 2015.
PMID- 28705253
TI - Trends in socioeconomic inequalities among adult male hardcore smokers in
Vietnam: 2010-2015.
AB - BACKGROUND: Despite male smokers being dominant in Vietnam, scarce evidence on
trends in socioeconomics inequalities among the hardcore male smokers is
available in the country. In this study, we aimed at assessing the trends in
socioeconomics inequalities among the hardcore smokers in adult male population
in Vietnam over a five-year period from 2010 to 2015. METHODS: We used data from
two rounds of the Vietnam Global Adult Tobacco Survey (GATS) conducted in 2010
and 2015. We included only men aged 25 years and above in the analysis. We
measured socioeconomic inequalities among hardcore smokers by calculating the
concentration index. We conducted multiple logistic regression analysis to
identify factors associated with hardcore smoking among men aged 25 years and
above. RESULTS: The results of this study showed that the prevalence of male
hardcore smokers aged 25 years and above in Vietnam was 9.5% in 2010 which
increased to 13.1% in 2015. The prevalence of male hardcore smokers declined in
the richest group from the 2010 level whereas it increased in the middle, poor
and poorest groups. All values of weighted concentration indices indicated that
the prevalence of male hardcore smokers occurred more among the poor men in
Vietnam in both 2010 and 2015. The socioeconomic inequalities in hardcore smokers
increased during 2010 and 2015. Residence in urban areas was significantly
associated with higher adult male hardcore smoking in our study. Belonging to the
age groups between 40 and 59 years, attaining primary and lower education, being
self-employed, belonging to the poorest household group, smoking being allowed at
home and no rule for smoking at home were associated with higher risk of being
hardcore smoker among adult males in Vietnam. CONCLUSIONS: We found increased
trends in socioeconomic inequalities in hardcore smoking among the study
population. Our study results indicate that existing smoking secession and
tobacco control policy and interventions need to be modified or new policies and
interventions should be introduced with the perspective of addressing
socioeconomic inequalities to have the desired impact. We recommend implementing
specific targeted interventions for vulnerable population groups for better
results.
PMID- 28705254
TI - Correlates of whole-blood polyunsaturated fatty acids among young children with
moderate acute malnutrition.
AB - BACKGROUND: Severe acute malnutrition (SAM) has been associated with low
polyunsaturated fatty acid (PUFA) status. However, investigations regarding PUFA
status and correlates in children with moderate acute malnutrition (MAM) from low
income countries are scarce. The aim of this study was to describe whole-blood
PUFA levels in children with moderate acute malnutrition (MAM) and to identify
correlates of PUFAs. METHODS: We conducted a cross-sectional study using baseline
data from a prospective nutritional intervention trial among 1609 children with
MAM aged 6-23 months in Burkina Faso,West Africa. Whole-blood PUFAs were measured
by gas chromatography and expressed as percent of total whole-blood fatty acids
(FA%). Potential correlates of PUFAs including infection, inflammation,
hemoglobin, anthropometry (difference between children diagnosed as having MAM
based on low mid-upper-arm-circumference (MUAC) only, low MUAC and weight-for
height z-score (WHZ), or low WHZ only) and diet were assessed by linear
regression adjusted for age and sex. RESULTS: Children with MAM had low
concentrations of whole-blood PUFAs, particularly n-3 PUFAs. Moreover, children
diagnosed with MAM based only on low MUAC had 0.32 (95% confidence interval (CI),
0.14; 0.50) and 0.40 (95% CI, 0.16; 0.63) FA% lower arachidonic acid (AA) than
those recruited based on both low WHZ as well as low MUAC and those recruited
with low WHZ only, respectively. Infection and inflammation were associated with
low levels of all long-chain (LC)-PUFAs, while hemoglobin was positively
associated with whole-blood LC-PUFAs. CONCLUSION: While PUFA deficiency was not a
general problem, overall whole-blood PUFA concentrations, especially of n-3
PUFAs, were low. Infection, inflammation, hemoglobin, anthropometry and diet were
correlates of PUFAs concentrations in children with MAM. TRIAL REGISTRATION: The
trial is registered at http://www.isrctn.com ( ISRCTN42569496 ).
PMID- 28705255
TI - Filarioid infections in wild carnivores: a multispecies survey in Romania.
AB - BACKGROUND: Filarioids are vector-borne parasitic nematodes of vertebrates. In
Europe, eight species of filarioids, including zoonotic species, have been
reported mainly in domestic dogs, and occasionally in wild carnivores. In
Romania, infections with Dirofilaria spp. and Acanthocheilonema reconditum are
endemic in domestic dogs. Despite the abundant populations of wild carnivores in
the country, their role in the epidemiology of filarioid parasites remains
largely unknown. The aim of the present study was to assess the host range,
prevalence and distribution of filarioid infections in wild carnivores present in
Romania. METHODS: Between May 2014 and February 2016, 432 spleen samples
originating from 14 species of wild carnivores have been tested for the presence
of DNA of three species of filarioids (D. immitis, D. repens and A. reconditum).
RESULTS: Overall 14 samples (3.24%) were molecularly positive. The most prevalent
species was D. immitis (1.62%), accounting for 50% (n = 7) of the positive
animals. The prevalence of D. repens was 1.39%, while that of A. reconditum was
0.23%. No co-infections were detected. Dirofilaria immitis DNA was detected in
five golden jackals, Canis aureus (7.58%), one red fox, Vulpes vulpes (0.33%),
and one wildcat, Felis silvestris (10%). The presence of D. repens DNA was
detected in two red foxes (0.66%), two golden jackals (3.03%), one grey wolf
(7.14%), and one least weasel, Mustela nivalis (33.33%). Acanthocheilonema
reconditum DNA was found only in one red fox (0.33%). CONCLUSION: The present
study provides molecular evidence of filarial infections in wild carnivore
species in Romania, suggesting their potential epidemiological role and reports a
new host species for D. repens.
PMID- 28705256
TI - Monocyte programmed death ligand-1 expression is an early marker for predicting
infectious complications in acute pancreatitis.
AB - BACKGROUND: Acute pancreatitis (AP) is a life-threatening disease that requires
early identification of patients at risk of developing infectious complications.
Immunosuppression is an initial event that is key to AP pathogenesis. The
programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) system
is reported to mediate evasion of host immune surveillance in many diseases;
however, the relationship between PD-1/PD-L1 expression and these parameters or
infectious complications in AP has not been elucidated. This study was conducted
to determine whether PD-1 and PD-L1 are upregulated and to reveal the
relationship between PD-1/PD-L1 expression and the development of infectious
complications in AP. METHODS: Sixty-three patients with AP and 32 sex- and age
matched healthy control subjects were prospectively enrolled. On days 1 and 3
after the onset of AP, we measured PD-1 expression in peripheral CD4+ T cells and
PD-L1 and human leukocyte antigen-DR (HLA-DR) expression in CD14+ monocytes using
flow cytometry. Plasma interleukin (IL)-10 levels were measured by enzyme-linked
immunosorbent assay. RESULTS: Compared with healthy volunteers, the percentages
of PD-1-expressing CD4+ lymphocytes and PD-L1-expressing CD14+ monocytes were
increased in patients with AP on days 1 and 3 after onset, especially those with
infectious complications. Moreover, increased PD-1/PD-L1 expression was
associated with increased occurrence of infectious complications, decreased
circulating lymphocytes, and increased plasma IL-10 concentration. Multivariate
regression analysis indicated that the increased percentage of PD-L1-expressing
CD14+ monocytes was an independent risk factor for infectious complications in
AP. Area under the ROC curve analysis showed the combination of Acute Physiology
and Chronic Health Evaluation II score and PD-L1 and HLA-DR expression in CD14+
monocytes had high accuracy in predicting infectious complications in patients
with AP. CONCLUSIONS: The PD-1/PD-L1 system plays an essential role in the early
immunosuppression of AP. PD-L1 expression in CD14+ monocytes may be a new marker
for predicting risk of infectious complications in patients with AP.
PMID- 28705257
TI - Single-stage transforaminal decompression, debridement, interbody fusion, and
posterior instrumentation for lumbosacral brucellosis.
AB - BACKGROUND: Spinal brucellosis is a less commonly reported infectious spinal
pathology. There are few reports regarding the surgical treatment of spinal
brucellosis in existing literature. This retrospective study was conducted to
determine the effectiveness of single-stage transforaminal decompression,
debridement, interbody fusion, and posterior instrumentation for lumbosacral
spinal brucellosis. METHODS: From February 2012 to April 2015, 32 consecutive
patients (19 males and 13 females, mean age 53.7 +/- 8.7) with lumbosacral
brucellosis treated by transforaminal decompression, debridement, interbody
fusion, and posterior instrumentation were enrolled. Medical records, imaging
studies, laboratory data were collected and summarized. Surgical outcomes were
evaluated based on visual analogue scale (VAS), Oswestry Disability Index (ODI)
and Japanese Orthopaedic Association (JOA) scale. The changes in C-reactive
protein (CRP) levels, erythrocyte sedimentation rate (ESR), clinical symptoms and
complications were investigated. Graft fusion was evaluated using Bridwell
grading criteria. RESULTS: The mean follow-up period was 24.9 +/- 8.2 months.
Back pain and radiating leg pain was relieved significantly in all patients after
operation. No implant failures were observed in any patients. Wound infection was
observed in two patients and sinus formation was observed in one patient. Solid
bony fusion was achieved in 30 patients and the fusion rate was 93.8%. The levels
of ESR and CRP were returned to normal by the end of three months' follow-up. VAS
and ODI scores were significantly improved (P < 0.05). According to JOA score,
surgical improvement was excellent in 22 cases (68.8%), good in 9 cases (28.1%),
moderate in 1 case (3.1%) at the last follow-up. CONCLUSIONS: Single-stage
transforaminal decompression, debridement, interbody fusion, and posterior
instrumentation is an effective and safe approach for lumbosacral brucellosis.
PMID- 28705258
TI - Fate bias during neural regeneration adjusts dynamically without recapitulating
developmental fate progression.
AB - BACKGROUND: Regeneration of neurons in the central nervous system is poor in
humans. In other vertebrates neural regeneration does occur efficiently and
involves reactivation of developmental processes. Within the neural retina of
zebrafish, Muller glia are the main stem cell source and are capable of
generating progenitors to replace lost neurons after injury. However, it remains
largely unknown to what extent Muller glia and neuron differentiation mirror
development. METHODS: Following neural ablation in the zebrafish retina, dividing
cells were tracked using a prolonged labelling technique. We investigated to what
extent extrinsic feedback influences fate choices in two injury models, and
whether fate specification follows the histogenic order observed in development.
RESULTS: By comparing two injury paradigms that affect different subpopulations
of neurons, we found a dynamic adaptability of fate choices during regeneration.
Both injuries followed a similar time course of cell death, and activated Muller
glia proliferation. However, these newly generated cells were initially biased
towards replacing specifically the ablated cell types, and subsequently
generating all cell types as the appropriate neuron proportions became re
established. This dynamic behaviour has implications for shaping regenerative
processes and ensuring restoration of appropriate proportions of neuron types
regardless of injury or cell type lost. CONCLUSIONS: Our findings suggest that
regenerative fate processes are more flexible than development processes.
Compared to development fate specification we observed a disruption in
stereotypical birth order of neurons during regeneration Understanding such
feedback systems can allow us to direct regenerative fate specification in injury
and diseases to regenerate specific neuron types in vivo.
PMID- 28705259
TI - "Just not all ice users do that": investigating perceptions and potential harms
of Australia's Ice Destroys Lives campaign in two studies.
AB - BACKGROUND: In 2015, the Australian government launched the media campaign Ice
Destroys Lives targeting crystal methamphetamine use. Previous research indicates
mass media campaigns may have harmful effects for people engaged in drug use.
This study investigated perceptions and harms of Ice Destroys Lives among adults
with a history of injecting drugs and young people. METHODS: This analysis
includes data from two studies: an online questionnaire with young people and in
depth interviews with adults who use crystal methamphetamine. Young people from
Victoria, Australia, were recruited through Facebook. We collected data on drug
use, campaign recognition and behaviours. Participants who recognised the
campaign indicated whether they agreed with five statements related to Ice
Destroys Lives. We compared campaign perceptions between young people who
reported ever using crystal methamphetamine and those who did not. Adults who use
crystal methamphetamine were sampled from the Melbourne injecting drug user
cohort study. We asked participants if they recognised the campaign and whether
it represented their experiences. RESULTS: One thousand twenty-nine young people
completed the questionnaire; 71% were female, 4% had used crystal methamphetamine
and 69% recognised Ice Destroys Lives. Three quarters agreed the campaign made
them not want to use ice. Ever using crystal methamphetamine was associated with
disagreeing with three statements including this campaign makes you not want to
use ice (adjusted odds ratio (AOR) = 4.3, confidence interval (CI) = 1.8-10.0),
this campaign accurately portrays the risks of ice use (AOR = 3.2, CI = 1.4-7.6)
and this campaign makes you think that people who use ice are dangerous (AOR =
6.6, CI = 2.2-19.8). We interviewed 14 people who used crystal methamphetamine;
most were male, aged 29-39 years, and most recognised the campaign. Participants
believed Ice Destroys Lives misrepresented their experiences and exaggerated "the
nasty side" of drug use. Participants felt the campaign exacerbated negative
labels and portrayed people who use crystal methamphetamine as "violent" and
"crazy". CONCLUSION: In our study, Ice Destroys Lives was widely recognised and
delivered a prevention message to young people. However, for people with a
history of crystal methamphetamine use, the campaign also reinforced negative
stereotypes and did not encourage help seeking. Alternative evidence-based
strategies are required to reduce crystal methamphetamine-related harms.
PMID- 28705260
TI - Identifying behavioural determinants for interventions to increase handwashing
practices among primary school children in rural Burundi and urban Zimbabwe.
AB - BACKGROUND: This article presents the development of a school handwashing
programme in two different sub-Saharan countries that applies the RANAS (risk,
attitudes, norms, ability, and self-regulation) systematic approach to behaviour
change. METHODS: Interviews were conducted with 669 children enrolled in 20
primary schools in Burundi and 524 children in 20 primary schools in Zimbabwe.
Regression analyses were used to assess the influence of the RANAS behavioural
determinants on reported handwashing frequencies. RESULTS: The results revealed
that, in both countries, a programme targeting social norms and self-efficacy
would be most effective. In Burundi, raising the children's perceived severity of
the consequences of contracting diarrhoea, and in Zimbabwe, increasing the
children's health knowledge should be part of the programme. CONCLUSIONS: The
school handwashing programme should create awareness of the benefits of
handwashing through educational activities, raise the children's ability and
confidence in washing hands at school through infrastructural improvements, and
highlight the normality of washing hands at school through events and poster
creation.
PMID- 28705261
TI - #cutting: Non-suicidal self-injury (NSSI) on Instagram.
AB - BACKGROUND: Social media presents an important means for social interaction,
especially among adolescents, with Instagram being the most popular platform in
this age-group. Pictures and communication about non-suicidal self-injury (NSSI)
can frequently be found on the internet. METHODS: During 4 weeks in April 2016, n
= 2826 (from n = 1154 accounts) pictures which directly depicted wounds on
Instagram were investigated. Those pictures, associated comments, and user
accounts were independently rated for content. Associations between
characteristics of pictures and comments as well as weekly and daily trends of
posting behavior were analyzed. RESULTS: Most commonly, pictures depicted wounds
caused by cutting on arms or legs and were rated as mild or moderate injuries.
Pictures with increasing wound grades and those depicting multiple methods of
NSSI generated elevated amounts of comments. While most comments were neutral or
empathic with some offering help, few comments were hostile. Pictures were mainly
posted in the evening hours, with a small peak in the early morning. While there
was a slight peak of pictures being posted on Sundays, postings were rather
evenly spread across the week. CONCLUSIONS: Pictures of NSSI are frequently
posted on Instagram. Social reinforcement might play a role in the posting of
more severe NSSI pictures. Social media platforms need to take appropriate
measures for preventing online social contagion.
PMID- 28705262
TI - Zinc Absorption from Representative Diet in a Chinese Elderly Population Using
Stable Isotope Technique.
AB - OBJECTIVE: To determine the dietary zinc absorption in a Chinese elderly
population and provide the basic data for the setting of zinc (Zn) recommended
nutrient intakes (RNI) for Chinese elderly people. METHODS: A total of 24 elderly
people were recruited for this study and were administered oral doses of 3 mg
67Zn and 1.2 mg dysprosium on the fourth day. The primary macronutrients, energy,
and phytic acid in the representative diet were examined based on the Chinese
National Standard Methods. Fecal samples were collected during the experimental
period and analyzed for zinc content, 67Zn isotope ratio, and dysprosium content.
RESULTS: The mean (+/- SD) zinc intake from the representative Chinese diet was
10.6 +/- 1.5 mg/d. The phytic acid-to-zinc molar ratio in the diet was 6.4. The
absorption rate of 67Zn was 27.9% +/- 9.2%. The RNI of zinc, which were
calculated by the absorption rate in elderly men and women, were 10.4 and 9.2
mg/d, respectively. CONCLUSION: This study got the dietary Zn absorption in a
Chinese elderly population. We found that Zn absorption was higher in elderly men
than in elderly women. The current RNI in elderly female is lower than our
finding, which indicates that more attention is needed regarding elderly females'
zinc status and health.
PMID- 28705263
TI - Antiviral Activity of Dual-acting Hydrocarbon-stapled Peptides against HIV-1
Predominantly Circulating in China.
AB - OBJECTIVE: New rationally designed i,i+7-hydrocarbon-stapled peptides that target
both HIV-1 assembly and entry have been shown to have antiviral activity against
HIV-1 subtypes circulating in Europe and North America. Here, we aimed to
evaluate the antiviral activity of these peptides against HIV-1 subtypes
predominantly circulating in China. METHODS: The antiviral activity of three
i,i+7-hydrocarbon-stapled peptides, NYAD-36, NYAD-67, and NYAD-66, against
primary HIV-1 CRF07_BC and CRF01_AE isolates was evaluated in peripheral blood
mononuclear cells (PBMCs). The activity against the CRF07_BC and CRF01_AE Env
pseudotyped viruses was analyzed in TZM-bl cells. RESULTS: We found that all the
stapled peptides were effective in inhibiting infection by all the primary HIV-1
isolates tested, with 50% inhibitory concentration toward viral replication
(IC50) in the low micromolar range. NYAD-36 and NYAD-67 showed better antiviral
activity than NYAD-66 did. We further evaluated the sensitivity of CRF01_AE and
CRF07_BC Env-pseudotyped viruses to these stapled peptides in a single-cycle
virus infectivity assay. As observed with the primary isolates, the IC50s were in
the low micromolar range, and NYAD-66 was less effective than NYAD-36 and NYAD
67. CONCLUSION: Hydrocarbon-stapled peptides appear to have broad antiviral
activity against the predominant HIV-1 viruses in China. This finding may provide
the impetus to the rational design of peptides for future antiviral therapy.
PMID- 28705264
TI - Uptake of HIV Self-testing among Men Who have Sex with Men in Beijing, China: a
Cross-sectional Study.
AB - OBJECTIVE: To examine HIV self-testing uptake and its determinates among men who
have sex with men (MSM) in Beijing, China. METHODS: A cross-sectional online
survey was conducted in Beijing, China in 2016. Participants were users of a
popular Chinese gay networking application and had an unknown or negative HIV
status. Univariate and multivariate logistic regression analyses were conducted
to examine factors associated with HIV self-testing based on adjusted odds ratio
(AOR) and 95% confidence interval (CI). RESULTS: Among the 5,996 MSM included in
the study, 2,383 (39.7%) reported to have used HIV self-testing kits. Willingness
to use an HIV self-test kit in the future was expressed by 92% of the
participants. High monthly income (AOR = 1.49; CI = 1.10-2.02; P = 0.010), large
number of male sex partners (? 2: AOR = 1.24; CI = 1.09-1.43; P = 0.002), sexual
activity with commercial male sex partners (? 2: AOR = 1.94; CI = 1.34 -2.82; P =
0.001), long-term drug use (AOR = 1.42; CI = 1.23-1.62; P < 0.001), and long-term
HIV voluntary counseling and testing (VCT) attendance (AOR = 3.62; CI = 3.11
4.22; P < 0.001) were all associated with increased odds of HIV self-testing
uptake. CONCLUSION: The nearly 40% rate of HIV self-testing uptake among MSM in
our sample was high. In addition, an over 90% willingness to use kits in the
future was encouraging. HIV self-testing could be an important solution to help
China achieve the global target of having 90% of all people living with HIV
diagnosed by 2020.
PMID- 28705265
TI - Comparison of Histological, Microbiological, and Molecular Methods in Diagnosis
of Patients with TBLN Having Different Anti-TB Treatment Background.
AB - OBJECTIVE: The influence of anti-tuberculosis (TB) treatment history on
tuberculous lymphadenitis (TBLN) diagnosis is unclear. Therefore, this study aims
to evaluate the diagnostic methods, including histology, microbiology, and
molecular tests, used for TBLN. METHODS: In this study, suspected patients with
TBLN and having different anti-TB treatment background were enrolled. All the
samples were tested simultaneously by histology, Ziehl-Neelsen (ZN) staining,
mycobacterial culture (culture), Xpert MTB/RIF (xpert), real-time PCR, and high
resolution melting curve PCR (HRM). Thereafter, the performance of these methods
on samples with different anti-TB treatment background was assessed. RESULTS: In
our study, 89 patients were prospectively included 82 patients with TBLN and 7
with other diseases. The overall sensitivities of Xpert, real-time PCR,
histology, ZN staining, and culture were 86.6%, 69.5%, 58.5%, 43.9%, and 22.0%,
respectively. The anti-TB treatment history revealed dramatic influences on the
sensitivity of culture (P < 0.0001). In fact, the treatment that lasted over 3
months also influenced the sensitivity of Xpert (P < 0.05). However, the
treatment history did not affect the performance of remaining tests (P > 0.05).
For rifampicin drug susceptibility test (DST), the anti-TB treatment showed only
significant influence on the success rate of culture DST (P = 0.001), but not on
those of Xpert and HRM tests (P > 0.05). CONCLUSION: Other tests as well as
culture should be considered for patients with TBLN having retreatment history or
over 1-month treatment to avoid false negative results.
PMID- 28705266
TI - A New Method for Blood NT-proBNP Determination Based on a Near-infrared Point of
Care Testing Device with High Sensitivity and Wide Scope.
AB - OBJECTIVE: To develop a rapid, highly sensitive, and quantitative method for the
detection of NT-proBNP levels based on a near-infrared point-of-care diagnostic
(POCT) device with wide scope. METHODS: The lateral flow assay (LFA) strip of NT
proBNP was first prepared to achieve rapid detection. Then, the antibody pairs
for NT-proBNP were screened and labeled with the near-infrared fluorescent dye
Dylight-800. The capture antibody was fixed on a nitrocellulose membrane by a
scribing device. Serial dilutions of serum samples were prepared using NT-proBNP
free serum series. The prepared test strips, combined with a near-infrared POCT
device, were validated by known concentrations of clinical samples. The POCT
device gave the output of the ratio of the intensity of the fluorescence signal
of the detection line to that of the quality control line. The relationship
between the ratio value and the concentration of the specimen was plotted as a
work curve. The results of 62 clinical specimens obtained from our method were
compared in parallel with those obtained from the Roche E411 kit. RESULTS: Based
on the log-log plot, the new method demonstrated that there was a good linear
relationship between the ratio value and NT-proBNP concentrations ranging from 20
pg/mL to 10 ng/mL. The results of the 62 clinical specimens measured by our
method showed a good linear correlation with those measured by the Roche E411
kit. CONCLUSION: The new LFA detection method of NT-proBNP levels based on the
near-infrared POCT device was rapid and highly sensitive with wide scope and was
thus suitable for rapid and early clinical diagnosis of cardiac impairment.
PMID- 28705267
TI - Acrylamide-induced Subacute Neurotoxic Effects on the Cerebral Cortex and
Cerebellum at the Synapse Level in Rats.
AB - OBJECTIVE: To investigate acrylamide (ACR)-induced subacute neurotoxic effects on
the central nervous system (CNS) at the synapse level in rats. METHODS: Thirty
six Sprague Dawley (SD) rats were randomized into three groups, (1) a 30 mg/kg
ACR-treated group, (2) a 50 mg/kg ACR-treated group, and (3) a normal saline (NS)
treated control group. Body weight and neurological changes were recorded each
day. At the end of the test, cerebral cortex and cerebellum tissues were
harvested and viewed using light and electron microscopy. Additionally, the
expression of Synapsin I and P-Synapsin I in the cerebral cortex and cerebellum
were investigated. RESULTS: The 50 mg/kg ACR-treated rats showed a significant
reduction in body weight compared with untreated individuals (P < 0.05). Rats
exposed to ACR showed a significant increase in gait scores compared with the NS
control group (P < 0.05). Histological examination indicated neuronal structural
damage in the 50 mg/kg ACR treatment group. The active zone distance (AZD) and
the nearest neighbor distance (NND) of synaptic vesicles in the cerebral cortex
and cerebellum were increased in both the 30 mg/kg and 50 mg/kg ACR treatment
groups. The ratio of the distribution of synaptic vesicles in the readily
releasable pool (RRP) was decreased. Furthermore, the expression levels of
Synapsin I and P-Synapsin I in the cerebral cortex and cerebellum were decreased
in both the 30 mg/kg and 50 mg/kg ACR treatment groups. CONCLUSION: Subacute ACR
exposure contributes to neuropathy in the rat CNS. Functional damage of synaptic
proteins and vesicles may be a mechanism of ACR neurotoxicity.
PMID- 28705268
TI - Description and Factors Affecting the Referral of Presumptive Tuberculosis
Patients in China.
AB - To describe and analyze the factors affecting the referral of presumptive
tuberculosis patients between health-care facilities that are not affiliated with
the National TB Control Program (NTP) and NTP-designated medical facilities in
China, we carried out a retrospective study based on data collected in the
Tuberculosis Information Management System in 2015. Out of 324,221 presumptive
pulmonary tuberculosis (PTB) cases reported by non-NTP health-care facilities,
302,006 (93.1%) reported cases successfully arrived at designated medical
facilities and 22,215 cases (6.9%) were lost to follow-up. The arrival rate of
presumptive cases among male patients (92.9%) was slightly lower than that among
female ones (93.7%), and this difference is statistically significant. The
majority (73.3%) of reported cases were local permanent residents. Migrants have
a higher risk of being lost to follow-up compared with local residents (adjusted
odds ratios 4.126 and 5.003, respectively). Compared with farmers and herdsmen,
pre-school children, unemployed laborers, retirees, and people with other
occupations (adjusted odds ratios 2.361, 1.274, 1.068, and 1.993, respectively)
had higher rates of loss to follow-up during the referral and tracing processes.
In conclusion, this study demonstrates that the high referral rate of presumptive
TB cases from non-NTP health-care facilities to designated medical facilities in
China is due to implementation of effective active case identification
strategies. In addition, migrant populations, pre-school children, unemployed
laborers, and retirees were identified as high-risk groups that contribute to the
loss to follow-up.
PMID- 28705269
TI - Regional Variations in Medication Usage for Cardiovascular Diseases at the
Community Level in China (PURE-China Study).
AB - We investigated the usage of secondary prevention drugs and traditional Chinese
medicine (TCM) products in individuals with cardiovascular diseases (CVDs) at the
community level in China. Among 2,407 participants with self-reported coronary
heart disease (CHD) and 872 with stroke, nearly 80% of individuals with CHD and
73% of individuals with stroke were not taking any proven secondary prevention
drug. However, 32.9% of them took TCM products. Patients with CVDs in rural areas
used less secondary prevention treatment, but more TCM products than their
counterparts in the urban regions. After adjusting for confounding factors, lower
rates of secondary prevention treatment were evident in Western China compared
with Eastern China, which was more developed. Systematic change is needed to
promote the development of evidence-based medicine at the community level in
China.
PMID- 28705270
TI - Serum Fetuin-A Levels and Thyroid Function inMiddle-aged and Elderly Chinese.
AB - Serum fetuin-A levels are reportedly elevated in hyperthyroidism. However, there
are few relevant epidemiologic studies. We conducted a cross-sectional study in
Songnan community, China in 2009 to investigate the association between serum
fetuin-A concentrations and thyroid function. A total of 2,984 participants aged
40 years and older were analyzed. Multivariable linear regression analysis
revealed that serum fetuin-A concentra- tions were positively associated with log
(free triiodothyronine) and were inversely associated with log (thyroid
peroxidase antibody) after adjustment (both P < 0.05). Compared with the
participants in the lowest tertile of free triiodo-thyronine and free thyroxine
level, those in the highest tertile had higher fetuin-A concentrations.
Additionally, high serum fetuin-A concentrations were related to high thyroid
function (odds ratio 1.27, 95% confidence interval 1.01-1.61), after adjustment
for conventional risk factors.
PMID- 28705271
TI - Molecular and Epidemiological Characterization of Infant Botulism in Beijing,
China.
AB - Laboratory-based pathogen isolation, identification, and toxicity determination
were performed on samples from a suspected case of infant botulism. Mice injected
with cultures generated from the enema sample and ingested Powered infant formula
(PIF) presented typical signs of botulism. Antitoxins to polyvalent botulinum
neurotoxins (BoNTs) and monovalent BoNT type B antitoxin had protective effects.
Clostridium botulinum isolated from the enema and residual PIF samples were
positive for type B toxin. Pulsed-field gel electrophoresis (PFGE) revealed that
the two strains of C. botulinum isolated from the two samples produced
indistinguishable pulsotypes. These findings confirmed this case of type B infant
botulism associated with the ingestion of PIF contaminated by type B C. botulinum
spores.
PMID- 28705272
TI - Measurement and Assessment of Physical Activity by Information and Communication
Technology.
AB - This study provides explorative insights into the information and communication
technology (ICT) for promoting the physical activity level. ICT has provided
innovative ideas and perspectives for PA measurement, assessment, evaluation and
health intervention. ICT that aims to increase exercise for the entire population
should be of a well-oriented and easy-to-use design with the options of tailored
and personalized feedback, coaching, and ranking and supporting; it should be
capable of setting goals and working with a schedule and be accompanied by a
website to provide overviews of the users' exercise results and progress.
PMID- 28705273
TI - Predatory Journals: Harmful to Patients, the Public, and the Integrity of
Scientific Research.
PMID- 28705274
TI - Why Me? Coping with the Uncertainties of Antigen Exposures in the Twenty-First
Century.
PMID- 28705275
TI - Telangiectasia Macularis Eruptiva Perstans: Report of Three Cases.
AB - Telangiectasia macularis eruptiva perstans (TMEP) is a rare, heterogeneous
disease of mast cell proliferation. The variable clinical presentation of TMEP,
coupled with its rarity, makes the recognition and diagnosis of this disease
difficult and challenging for clinicians. The histopathologic findings with
hematoxylin and eosin staining that distinguish TMEP from a normal skin biopsy
can be so subtle that confirmation of the diagnosis with additional special
stains (c-Kit, Giemsa, toluidine blue) is strongly recommended. We describe three
cases that highlight the variable clinical presentation of TMEP. One patient
experienced only a localized skin manifestation, another an aggressive clinical
course with systemic involvement, and a third diffuse skin involvement with mild
fatigue, muscle pain, and weight gain.
PMID- 28705276
TI - Evaluation of Autoimmune Bullous Diseases in Elderly Patients in Iran: A 10-Year
Retrospective Study.
AB - Autoimmune bullous diseases (ABDs) are uncommon but significant skin disorders
with relatively high morbidity and mortality. Some surveys have been carried out
to describe the spectrum of ABDs in a region, but this is the first that has
focused on ABDs in elderly patients. This study was conducted to determine the
clinicoepidemiologic features of ABDs in elderly patients. Medical records of all
ABD patients with disease onset after the age of 60 years who presented to the
Autoimmune Bullous Diseases Research Center, Tehran, Iran between April 2003 and
March 2013 were reviewed. Patients with dermatitis herpetiformis were not
included. During the 10-year period studied, 296 patients with ABD and disease
onset after 60 years of age were diagnosed. Bullous pemphigoid (BP) was observed
to be the most common ABD (48.3%), followed by pemphigus vulgaris (45.3%),
pemphigus foliaceus (3.7%), mucous membrane pemphigoid (1.4%), paraneoplastic
pemphigus (0.7%), epidermolysis bullosa acquisita (0.3%), and linear IgA bullous
disease (0.3%). A predominance in women was observed for total ABDs, BP, and
pemphigus vulgaris. Although Iran is known to have a high prevalence of
pemphigus, BP is the most frequent ABD among elderly patients in Iran,
highlighting the importance of the clinical diagnosis of BP in elderly patients.
PMID- 28705277
TI - Spectrum of Autoimmune Bullous Diseases in the Middle East: A 15-Year Review.
AB - Characteristics of autoimmune bullous diseases (AIBDs) show wide geographic
variation. The aim of this study was to determine retrospectively the
characteristics of patients with AIBD admitted to Hotel-Dieu de France Hospital
in Beirut, Lebanon, between 1999 and 2014 and to compare them with those from
other areas in the Middle East, the Far East, Asia, North Africa, Europe, and
North America. For the patients with AIBDs and who were hospitalized at a major
tertiary referral center between 1999 and 2004, we studied demographics,
diagnosis, length of stay, department/floor, comorbidities, clinical features, in
hospital evolution, diagnostic tests, and treatment. Bullous pemphigoides was the
most frequent bullous disease in Lebanon. This and other findings contrast with
those of studies conducted in regional countries. This is the first report of
AIBD from the Middle Eastern region.
PMID- 28705280
TI - Smoking and the Skin.
AB - Smoking has been identified as a habit that carries great health risks. This
review focuses on the consequences of smoking for skin diseases, treatment
responses, and outcome. Diversification of the tobacco industry has led to new
challenges, and careful documentation of risks for healthy skin is a continuing
challenge.
PMID- 28705278
TI - History of Seborrheic Dermatitis: Conceptual and Clinico-Pathologic Evolution.
AB - Seborrheic dermatitis is an inflammatory and chronic disease with a high
incidence and prevalence (1% to 3% in the general population, 3% to 5% in young
adults, and 40% to 80% in HIV-positive individuals). Although the condition was
first described in 1887, its clinical aspects and clinical forms have still not
been well individualized, nor has its etiopathogenesis been fully elucidated. The
disease, despite having clinical features similar to dermatitis, does not have
the same histopathologic features or the same progressive clinical behavior. This
contribution reviews the history of seborrheic dermatitis.
PMID- 28705283
TI - Infundibulocystic Basal Cell Carcinomas and the SUFU Snafu.
PMID- 28705282
TI - Fine and Benign, Until It Becomes Malignant: The Enigmatic Keratoacanthoma.
PMID- 28705284
TI - Picturing in Dermatology-From Wax Models to Teledermatology, Part I.
PMID- 28705285
TI - Childhood-Onset Keratosis Lichenoides Chronica Accompanied by Severe Hair Loss.
AB - A 37-year-old woman attended the dermatology outpatient clinic because of recent
hair loss from the eyebrows and axillae. Her past medical history revealed mild
generalized erythema and hyperpigmented papules and plaques since childhood. On
dermatologic examination, there were flat-topped, purple to brown hyperkeratotic
lichenoid papules and linear plaques on the elbows, trunk, and buttocks, some of
which coalesced into hyperpigmented reticular plaques on the axillae, neck, and
groin. Mild erythema was noted. There was thinning and loss of hair of the
eyebrows; severe loss of hair was noted in the axillae and genital regions
(Figure 1). One of the lichenoid papules was biopsied. The specimen showed
histopathologic findings of focal parakeratosis, irregular acanthosis, an
increased granular layer, and focal vacuolar degeneration of the basal layer.
Necrotic keratinocytes were also observed. Hyalinization and abundant melanin in
the papillary dermis and marked congestion of blood vessels were noted (Figure
2). Clinicopathologic correlation of the case was consistent with keratosis
lichenoides chronica (KLC).
PMID- 28705286
TI - Giant Pigmented Squamous Cell Carcinoma in Situ: A Diagnostic and Therapeutic
Challenge.
AB - A 91-year-old Hispanic man with a diffuse large B-cell lymphoma of the stomach
that was currently being treated with immunosuppressive therapy was referred for
evaluation of a biopsy-proven squamous cell carcinoma in situ (SCCis) on the left
mid-region of his back. The lesion had apparently been present at birth and had
recently started to itch, become red, and progressively enlarge.
PMID- 28705287
TI - Generalized Discoid Lupus Erythematosus as the Presenting Sign of Small Cell Lung
Carcinoma.
AB - A 46-year-old woman with a 30 pack-year smoking history presented with a
worsening eruption on the left cheek that failed to improve with metronidazole
gel. The cutaneous eruption spread to most of her face and did not respond to a
brief tapering course of prednisone. During the initial evaluation at our
institution, approximately 6 weeks after the onset of the cutaneous eruption, the
patient had erythematous, crusted plaques on her face and scalp (Figure 1A); they
were also present on the V-area of the anterior aspect of the neck and upper
region of the chest, the shoulders, and the arms, with isolated lesions on the
trunk and legs. Her oral mucosa had erythematous erosions on the hard palate and
gingivae. A review of systems revealed pain and burning of her skin lesions, but
no muscle weakness or other systemic clinical manifestations. The differential
diagnosis included autoimmune connective tissue disease, pemphigus foliaceous,
sarcoidosis, lichen planus, phototoxic drug eruption, and eczema herpeticum.
PMID- 28705288
TI - Chemical Tattoo Treatment Leading to Systemic Cobalt Hypersensitivity.
AB - An otherwise healthy 36-year-old Caucasian woman, without prior history of atopic
dermatitis or eczema, presented to an outside dermatologist with a generalized,
severely pruritic eruption involving the entire body except the face. One month
previously, she had used a 50% trichloroacetic acid tattoo removal solution on a
blue-colored tattoo on the medial aspect of the left ankle. The patient's
eruption persisted for 7 months, and after several attempts to slowly taper her
prednisone dose, she presented to our institution. On physical examination, there
was a 3-cm erythematous, lichenified plaque surrounding the tattoo (Figure). On
the trunk and upper regions of the arms, there were scattered, 1- to 2-cm,
nummular patches and plaques. Biopsy of a truncal lesion revealed spongiotic
pustules with a mixed dermal infiltrate and scattered eosinophils, consistent
with subacute spongiotic dermatitis.
PMID- 28705289
TI - Association of Piebaldism with Cafe-au-Lait Macules.
AB - A 45-day-old infant was brought by his parents to the dermatology outpatient
department with chief complaints of asymptomatic, depigmented lesions that had
been present on his skin since birth. On mucocutaneous examination, large
rhomboid-shaped depigmented macules were noted on the abdomen and lower
extremities bilaterally (Figure 1). A depigmented macule was present on the
forehead, with white hair (leukotrichia; a "developing forelock") (Figure 2).
Three hyperpigmented lesions (cafe-au-lait macules [CALMs]) were also noted on
the chest (Figure 1a). There was no history of consanguinity, and the family
history was negative. The infant was otherwise normal for his age. A diagnosis of
"piebaldism with CALMs" was made, and his parents were counseled about the
disease and its progression, and possible treatment options as the child grew.
They were also informed about a currently unquantifiable risk of future
development of Legius syndrome or neurofibromatosis type 1 (NF1), and were
counseled for regular follow-up.
PMID- 28705290
TI - Crossed Total Hemiatrophy Associated with Atrophoderma of Pasini-Pierini.
AB - A 45-year-old Chinese man had begun to show asymmetry of the face 30 years
previously. Subsequently, he developed visual extinction of the right eye, slight
numbness, and weakness of the left extremities. Simultaneously, multiple atrophic
brownish patches occurred on his side. He denied prior trauma or tick bites at
those sites. There was no report of preceding redness, induration, or a history
of trauma. The atrophic lesions extended and enlarged slowly. Ten years
previously, some brownish patches with normal texture had appeared on the right
side of the trunk. There was no further progression of the lesions. In November
2010, the patient consulted our department for the final diagnosis and prognosis
of his disease. He did not suffer from epileptic seizures and had no history of a
tick bite or Lyme disease.
PMID- 28705291
TI - Lichenoid Dermatitis in an Adult with Immune Dysregulation, Polyendocrinopathy,
Enteropathy, X-Linked (IPEX) Syndrome.
AB - A 23-year-old man presented to our practice with erythroderma and an unusual
retiform eruption, along with alopecia universalis and nail dystrophy. He had had
no skin findings at birth, but since early infancy had had localized eczematous
eruptions of his skin. At 10 years of age, he had developed a generalized
eczematous flare requiring hospitalization, and another generalized episode
occurred in October 2010. He was prescribed prednisone 60 mg daily, which
initially provided an improvement, but tapering of the corticosteroid resulted in
another generalized flare.
PMID- 28705292
TI - A Case of Ischemia-Induced Perianal Ulceration Mimicking Pyoderma Gangrenosum.
AB - A 68-year-old woman, with a 75-pack-year smoking history and a history of chronic
excess alcohol intake, presented with a 5-week history of worsening perianal pain
and ulceration. She recently had an inpatient admission with back pain and
urinary tract infection during which she developed diarrhea and fecal
incontinence. Initially, the perianal ulceration was diagnosed as severe irritant
contact dermatitis and treated with barrier creams and topical clobetasone 17
butyrate 0.05% weight for weight, oxytetracycline 3.0% weight for weight and
nystatin cream (Trimovate(r)). Despite this, the ulceration progressed, resulting
in hospital readmission 1 month later. There was no history of consumption of
nicorandil (an antianginal therapy), of recurrent oral ulcers, or of inflammatory
bowel disease. On examination, there were multiple areas of deep, sloughy
ulceration bilaterally around the perianal and buttock regions with erythematous
and violaceous edges (Figure 1). Complete blood count, blood film, rheumatoid
factor, autoimmune and vasculitic profile, hepatitis screen, immunoglobulins and
plasma protein electrophoresis were all normal. Punch biopsy revealed scanty
dermal perivascular inflammatory cell infiltrate and occasional neutrophils
(Figure 2). No evidence of granulomata, dysplasia, malignancy, or Langerhans
histiocytes was identified, and periodic acid-Schiff staining was negative.
PMID- 28705293
TI - Skin and Psyche.
PMID- 28705294
TI - Molecular Mechanisms of Skin Aging and Age-Related Diseases.
PMID- 28705295
TI - Strength Training for Women as a Vehicle for Health Promotion at Work.
AB - BACKGROUND: Women, on average, have less muscle strength than men. This
anthropometric-physiological trait may make them more vulnerable to ex - cessive
physical strain, injury, and inability to work. Strength training is used for
preventive health maintenance and to lessen musculoskeletal symptoms. In this
context, we studied whether the degree of muscle strength has any effect on
women's health in everyday working life, and also the effects of strength
training for women on their health in the workplace. METHODS: We systematically
searched the PubMed/MEDLINE, Embase, CINAHL, Web of Science, CENTRAL, and SPOLIT
databases for pertinent publications, in accordance with the PRISMA criteria for
literature searches. We analyzed all of the retrieved randomized controlled
trials conducted on women aged 18 to 65 to determine the effects of training on
muscle strength, physical performance ability, and health-related parameters
including body composition, musculo - skeletal pain, and subjective well-being.
RESULTS: We did not find any studies that provided answers to the first question.
As for the second question, the selection criteria were met by 12 of the 4969
retrieved studies, which dealt with the effect of strength training on health in
the occupational environment and involved a total of 1365 female subjects. These
studies were carried out in heterogeneous subject groups, with a variety of
overlapping interventions consisting of both strength and endurance training.
Significantly increased strength was found in all studies, as was a reduction of
pain in all of the studies where this question was asked. Inconsistent results
were obtained with respect to body weight, body composition, and subjective well
being. CONCLUSION: The interventions that were conducted in these studies
succeeded in increasing strength and reducing pain, even when the training was
brief and of low intensity. This was true not only for women working in
occupations requiring unusual physical strength, but also for those in sedentary
occupations. The small number of studies performed on this subject to date is
surprising in view of the high prevalence of musculoskeletal symptoms in women.
PMID- 28705296
TI - Free Air in the Abdomen.
PMID- 28705297
TI - The Diagnosis and Treatment of Behavioral Disorders in Dementia.
AB - BACKGROUND: Behavioral disorders such as aggressiveness, agitation, delusions,
disinhibition, affect lability, and apathy arise in more than 90% of patients
with dementia. Behavioral disorders are a major challenge and the greatest stress
factor in everyday life for nursing personnel and for family members caring for
the patient. METHODS: This review is based on relevant publications retrieved by
a selective literature search in the PubMed, Cochrane Library, and German S3
guideline databases with the search terms "behavioral disorders," "non-cognitive
disorders," and "challenging behavior," in conjunction with "dementia" and
"behavioral and psychological symptoms of dementia." RESULTS: Behavioral
disorders regularly accompany dementing illness and have identifiable and
treatable somatic and environment-related causes. They should be treated
symptomatically, both with non-pharmacological measures and with drugs. Memory
therapy (d = 0.47), ergotherapy (d = 0.72), music therapy (d = 0.62), and
physical exercise (d = 0.68) are effective, as are antidementia drugs
(galantamine: p = 0.04, donepezil: p = 0.01, rivastigmine: p = 0.02, memantine: p
= 0.004). Risperidone is the drug of choice to combat agitation and
aggressiveness (d = 0.33) as well as dementia and hallucinations (d = 0.5).
Citalopram can be recommended for the treatment of depression in patients with
dementia (p = 0.05). CONCLUSION: Because of an improved evidence base, the latest
version of the German S3 guideline on the diagnosis and treatment of dementia
places greater emphasis on non-pharmacological treatments for behavioral
disorders in dementia than it did in the past. The global efficacy of such
treatments against behavioral disorders is well documented. Nonetheless, because
of the heterogeneity of interventions and varying standards of assessment, the
evidence for the utility of certain specific methods in the treatment of specific
behavioral disorders is still limited. More research is needed in this area.
PMID- 28705298
TI - Methamphetamine-Related Disorders.
AB - BACKGROUND: Methamphetamine is considered more dangerous than other stimulants
because of its acute complications, long-term neurotoxicity, and potential for
drug dependence. Until now, there have been no evidence-based guidelines for the
treatment of methamphetamine-related disorders, either in Germany or abroad.
METHODS: A systematic literature search was performed on the treatment of
methamphetamine-related disorders. Based on this literature review, a
multidisciplinary expert panel developed recommendations using the nominal group
technique. RESULTS: The evidence base for the treatment of methamphetamine
related disorders is sparse. The efficacy of psychotherapeutic techniques such as
cognitive behavioral therapy and contingency management and the efficacy of
complex, disorder-specific treatment programs have been proven in ran - domized
controlled trials, but it remains unclear which method is best. Persons carrying
a diagnosis of substance abuse should be offered psychotherapy. Structured
exercise programs, whether self-directed or professionally led, can improve
addiction-specific endpoints as well as comorbid disorders and should, therefore,
be offered as well. Pharmacotherapy has shown little to no effect in relatively
low-quality clinical trials with low case numbers and high dropout rates, and
therefore only a few weak recommendations were made. These include tranquilizers
for the short-term treatment of agitation and atypical antipsychotics if
necessary. Attempts to substitute other substances, such as methylphenidate or
dexamphetamine, for methamphetamine have not yielded any robust evidence to date.
Sertraline should not be administered due to serious adverse events. CONCLUSION:
Many of the recommendations in the guideline are made with a weak grade of
recommendation because of the poor evidence base and the modest size of the
reported therapeutic effects. In acute situations, symptomoriented treatment is
recommended. Psychotherapy and exercise should be offered as well.
PMID- 28705299
TI - Dehydration-The Pharynx is Affected As Well.
PMID- 28705300
TI - Prescribing Behavior Is a Cause.
PMID- 28705301
TI - In Reply.
PMID- 28705302
TI - The "value" of immune-checkpoint inhibitors for advanced lung cancer.
PMID- 28705303
TI - Nonpharmacologic airway clearance techniques - Is there trustworthy evidence for
their clinical usefulness?
PMID- 28705304
TI - Clinical practice of acute respiratory distress syndrome in Japan: A nationwide
survey and scientific evidences.
AB - BACKGROUND: There has been limited information about epidemiology and clinical
practice of acute respiratory distress syndrome (ARDS) in Japan. METHODS: An
invitation letter to the web-based survey was mailed to all 871 board certified
hospitals of the Japanese Respiratory Society. The questionnaires were designed
to collect data on epidemiology and clinical practice of ARDS, including
diagnostic measures and therapeutics. RESULTS: Within 4 months of the survey
period, valid responses were obtained from 296 (34%) hospitals. The incidence of
ARDS was estimated to be 3.13 cases/100 hospital beds or 1.91 cases/ICU bed per
year. The most frequent underlying disease was pneumonia (34%), followed by
sepsis (29%). In hospitals with fewer ICU beds, pulmonologists tended to be in
charge of management of ARDS patients. Routine diagnostic measures included
computed tomography of the chest (69.6% of the hospitals) and Swan-Ganz
catheterization was rarely performed for diagnosis. In 87.4% of the hospitals,
non-invasive ventilation was applied to management of ARDS patients, especially
those with mild disease. Prone positioning and extracorporeal membrane
oxygenation (ECMO) for ARDS patients was more widely adopted in hospitals with
larger numbers of ICU beds and intensivists. In 58.2% of the responding
hospitals, corticosteroid was considered as a treatment option for ARDS, among
which pulse therapy was routinely introduced to ARDS patients in 35.4%.
CONCLUSIONS: The incidence of ARDS in Japan was estimated to be lower than that
in the recent international study. The scale and equipment of hospitals and the
number of intensivists might influence clinical practice of ARDS.
PMID- 28705305
TI - Clinical characteristics of Japanese candidates for lung transplant for
interstitial lung disease and risk factors for early death while on the waiting
list.
AB - BACKGROUND: Lung transplants have produced very favorable outcomes for patients
with interstitial lung disease (ILD) in Japan. However, because of the severe
donor lung shortage, patients must wait approximately 2.5 years before they can
undergo transplantation and many candidates die before allocation. We reveal the
clinical characteristics of Japanese patients with ILD who are candidates for
lung transplants and the risk factors for early death while on the waiting list.
METHODS: We retrospectively reviewed the clinical data of patients registered in
the Japan Organ Transplant Network from Okayama University Hospital who are
candidates for cadaveric lung transplants for ILD between 1999 and 2015. RESULTS:
Fifty-three patients with ILD were included (24 patients with idiopathic
pulmonary fibrosis and 29 others). They had severe pulmonary dysfunction and low
exercise tolerability. The median waiting time for transplantation was 462 days,
and 22 patients died before allocation. Patients who died before 462 days without
undergoing transplantation had more severe dyspnea, shorter 6-minute walk
distance (6MWD), and lower performance status than those who waited >=462 days.
CONCLUSIONS: Japanese candidates for cadaveric lung transplants for ILD have
severe pulmonary dysfunction. Severe dyspnea, short 6MWD, and low performance
status are risk factors for early death while on the waiting list.
PMID- 28705306
TI - Riociguat for patients with chronic thromboembolic pulmonary hypertension:
Usefulness of transitioning from phosphodiesterase type 5 inhibitor.
AB - BACKGROUND: Riociguat, the first approved drug for patients with chronic
thromboembolic pulmonary hypertension (CTEPH), is a soluble guanylate cyclase
(sGC) Stimulator. It directly stimulates sGC independently of nitric oxide (NO)
and increases sGC sensitivity for NO. The safety and efficacy of transitioning
from a phosphodiesterase 5 inhibitor (PDE5i) to riociguat is unknown. METHODS AND
RESULTS: Twenty-three patients were prospectively enrolled: 8 symptomatic
patients with inadequate clinical responses to PDE5i were changed to riociguat
(transitioned group); 15 started riociguat anew (new or add-on group). We
analyzed the change from baseline to 6-12 months of riociguat treatment for the 6
minute walk distance (6MWD), mean pulmonary arterial pressure (mPAP), pulmonary
vascular resistance (PVR), cardiac index (CI), partial pressure of oxygen in
arterial blood (PaO2), brain natriuretic peptide (BNP), World Health Organization
(WHO) functional class, safety and adverse events. The mPAP, BNP and WHO
functional class significantly improved in total. In the transitioned group, BNP
significantly decreased by -116.5+/-188.6pg/ml (P=0.0156). The 6MWD, mPAP, PVR,
CI, and PaO2 improved but not significantly. The baseline condition was
significantly more severe in the transitioned than in the new or add-on group. No
patients discontinued riociguat. Relatively rapid transitioning from PDE5i to
riociguat was safe under careful observation. CONCLUSIONS: Transitioning to
riociguat may be safe and effective in CTEPH patients with inadequate clinical
responses to PDE5i.
PMID- 28705307
TI - A new method for enhanced expectoration of sputum by vibratory stimulation of the
cervical trachea.
AB - BACKGROUND: Expectoration of sputum can be difficult for patients with
respiratory conditions such as chronic obstructive pulmonary disease, chronic
bronchitis, or bronchiectasis because of the effects of decreased pulmonary
function, respiratory muscle fatigue, altered sputum properties, and impaired
ciliary function. We developed a new method for the vibratory stimulation of the
cervical trachea and this study aimed to compare it with the Acapella (a current
oscillation device) method. METHODS: Patients with chronic productive cough and
difficulty with expectoration were recruited for the study. The tracheal
vibration and Acapella methods were applied for 4 weeks each, according to a
crossover design with an intervening 4-week washout period. To perform the
tracheal vibration method, an electronic artificial larynx (Yourtone(r)) was
applied to the cervical trachea for up to 5minutes. Patient preference for the
two devices was determined from the performance scores recorded for each device
and by using a visual analogue scale. RESULTS: Twelve patients were recruited in
the study. According to the performance scores assigned by the subjects, the
tracheal vibration method was effective in 9 patients, while the Acapella method
was effective in 10 patients. Both methods were effective in 8 patients, among
whom the tracheal vibration method was more effective in 5 patients. Both methods
were found to be ineffective in 1 patient. CONCLUSIONS: The tracheal vibration
method may be effective at removing central airway sputum and does not require
repeated forced expiratory effort, which can otherwise cause exhaustion in
patients with decreased lung function. Further investigation is required to
confirm its use as a new oscillation technique.
PMID- 28705308
TI - Primary Sjogren's syndrome with Waldenstrom's macroglobulinemia presenting as
unilateral bloody pleural effusion.
PMID- 28705309
TI - Comparison of the aerosol velocity of two Respimat(r) soft mist inhalers and two
pressurized metered-dose inhalers for short-acting muscarinic antagonists.
PMID- 28705311
TI - Approaching Automated 3-Dimensional Measurement of Atherosclerotic Plaque Volume.
PMID- 28705310
TI - Subclinical Atherosclerosis Burden by 3D Ultrasound in Mid-Life: The PESA Study.
AB - BACKGROUND: Detection of subclinical atherosclerosis improves risk prediction
beyond cardiovascular risk factors (CVRFs) and risk scores, but quantification of
plaque burden may improve it further. Novel 3-dimensional vascular ultrasound
(3DVUS) provides accurate volumetric quantification of plaque burden. OBJECTIVES:
The authors evaluated associations between 3DVUS-based plaque burden and CVRFs
and explored potential added value over simple plaque detection. METHODS: The
authors included 3,860 (92.2%) PESA (Progression of Early Subclinical
Atherosclerosis) study participants (age 45.8 +/- 4.3 years; 63% men). Bilateral
carotid and femoral territories were explored by 3DVUS to determine the number of
plaques and territories affected, and to quantify global plaque burden defined as
the sum of all plaque volumes. Linear regression and proportional odds models
were used to evaluate associations of plaque burden with CVRFs and estimated 10
year cardiovascular risk. RESULTS: Plaque burden was higher in men (63.4 mm3
[interquartile range (IQR): 23.8 to 144.8 mm3] vs. 25.7 mm3 [IQR: 11.5 to 61.6
mm3] in women; p < 0.001), in the femoral territory (64 mm3 [IQR: 27.6 to 140.5
mm3] vs. 23.1 mm3 [IQR: 9.9 to 48.7 mm3] in the carotid territory; p < 0.001),
and with increasing age (p < 0.001). Age, sex, smoking, and dyslipidemia were
more strongly associated with femoral than with carotid disease burden, whereas
hypertension and diabetes showed no territorial differences. Plaque burden was
directly associated with estimated cardiovascular risk independently of the
number of plaques or territories affected (p < 0.01). CONCLUSIONS: 3DVUS
quantifies higher plaque burden in men, in the femoral territory, and with
increasing age during midlife. Plaque burden correlates strongly with CVRFs,
especially at the femoral level, and reflects estimated cardiovascular risk more
closely than plaque detection alone. (Progression of Early Subclinical
Atherosclerosis [PESA] Study; NCT01410318).
PMID- 28705312
TI - Community-Based Lifestyle Intervention in Patients With Coronary Artery Disease:
The RESPONSE-2 Trial.
AB - BACKGROUND: Among patients with coronary artery disease (CAD), improvement of
lifestyle-related risk factors (LRFs) reduces cardiovascular morbidity and
mortality. However, modification of LRFs is highly challenging. OBJECTIVES: This
study sought to evaluate the impact of combining community-based lifestyle
programs with regular hospital-based secondary prevention. METHODS: The authors
performed a randomized controlled trial of nurse-coordinated referral of patients
and their partners to 3 widely available community-based lifestyle programs, in
15 hospitals in the Netherlands. Patients admitted for acute coronary syndrome
and/or revascularization, with >=1 LRF (body mass index >27 kg/m2, self-reported
physical inactivity, and/or smoking) were included. All patients received
guideline-based usual care. The intervention was based on 3 lifestyle programs
for weight reduction, increasing physical activity, and smoking cessation. The
primary outcome was the proportion of success at 12 months, defined as
improvement in >=1 qualifying LRF using weight (>=5% reduction), 6-min-walking
distance (>=10% improvement), and urinary cotinine (200 ng/ml detection limit)
without deterioration in the other 2. RESULTS: The authors randomized 824
patients. Complete data on the primary outcome were available in 711 patients.
The proportion of successful patients in the intervention group was 37% (133 of
360) compared with 26% (91 of 351) in the control group (p = 0.002; risk ratio:
1.43; 95% confidence interval: 1.14 to 1.78). In the intervention group, partner
participation was associated with a significantly greater success rate (46% vs.
34%; p = 0.03). CONCLUSIONS: Among patients with coronary artery disease, nurse
coordinated referral to a comprehensive set of community-based, widely available
lifestyle interventions, with optional partner participation, leads to
significant improvements in LRFs. (RESPONSE-2: Randomised Evaluation of Secondary
Prevention by Outpatient Nurse SpEcialists 2; NTR3937).
PMID- 28705313
TI - Using Commercial Programs for Lifestyle Intervention: Not Reinventing the Wheel.
PMID- 28705315
TI - Mending the Soul When the Heart Is Broken.
PMID- 28705314
TI - Palliative Care in Heart Failure: The PAL-HF Randomized, Controlled Clinical
Trial.
AB - BACKGROUND: Advanced heart failure (HF) is characterized by high morbidity and
mortality. Conventional therapy may not sufficiently reduce patient suffering and
maximize quality of life. OBJECTIVES: The authors investigated whether an
interdisciplinary palliative care intervention in addition to evidence-based HF
care improves certain outcomes. METHODS: The authors randomized 150 patients with
advanced HF between August 15, 2012, and June 25, 2015, to usual care (UC) (n =
75) or UC plus a palliative care intervention (UC + PAL) (n = 75) at a single
center. Primary endpoints were 2 quality-of-life measurements, the Kansas City
Cardiomyopathy Questionnaire (KCCQ) overall summary and the Functional Assessment
of Chronic Illness Therapy-Palliative Care scale (FACIT-Pal), assessed at 6
months. Secondary endpoints included assessments of depression and anxiety
(measured via the Hospital Anxiety and Depression Scale [HADS]), spiritual well
being (measured via the FACIT-Spiritual Well-Being scale [FACIT-Sp]),
hospitalizations, and mortality. RESULTS: Patients randomized to UC + PAL versus
UC alone had clinically significant incremental improvement in KCCQ and FACIT-Pal
scores from randomization to 6 months (KCCQ difference = 9.49 points, 95%
confidence interval [CI]: 0.94 to 18.05, p = 0.030; FACIT-Pal difference = 11.77
points, 95% CI: 0.84 to 22.71, p = 0.035). Depression improved in UC + PAL
patients (HADS-depression difference = -1.94 points; p = 0.020) versus UC-alone
patients, with similar findings for anxiety (HADS-anxiety difference = -1.83
points; p = 0.048). Spiritual well-being was improved in UC + PAL versus UC-alone
patients (FACIT-Sp difference = 3.98 points; p = 0.027). Randomization to UC +
PAL did not affect rehospitalization or mortality. CONCLUSIONS: An
interdisciplinary palliative care intervention in advanced HF patients showed
consistently greater benefits in quality of life, anxiety, depression, and
spiritual well-being compared with UC alone. (Palliative Care in Heart Failure
[PAL-HF]; NCT01589601).
PMID- 28705316
TI - Cell-Specific Pathways Supporting Persistent Fibrosis in Heart Failure.
AB - BACKGROUND: Only limited data exist describing the histologic and
noncardiomyocyte function of human myocardium in end-stage heart failure (HF).
OBJECTIVES: The authors sought to determine changes in noncardiomyocyte cellular
activity in patients with end-stage HF after left ventricular assist device
(LVAD)-induced remodeling to identify mechanisms impeding recovery. METHODS:
Myocardium was obtained from subjects undergoing LVAD placement and/or heart
transplantation. Detailed histological analyses were performed, and, when
feasible, mononuclear cells were isolated from fresh, dissociated myocardium for
quantitative reverse transcription polymerase chain reaction studies.
Echocardiographic and catheterization data were obtained during routine care.
RESULTS: Sixty-six subjects were enrolled; 54 underwent 8.0 +/- 1.2 months of
LVAD unloading. Despite effective hemodynamic unloading and remodeling, there
were no differences after LVAD use in capillary density (0.78 +/- 0.1% vs. 0.9 +/
0.1% capillary area; n = 42 and 28, respectively; p = 0.40), cardiac fibrosis
(25.7 +/- 2.4% vs. 27.9 +/- 2.4% fibrosis area; n = 44 and 31, respectively; p =
0.50), or macrophage density (80.7 +/- 10.4 macrophages/mm2 vs. 108.6 +/- 15
macrophages/mm2; n = 33 and 28, respectively; p = 0.1). Despite no change in
fibrosis or myofibroblast density (p = 0.40), there was a 16.7-fold decrease (p <
0.01) in fibroblast-specific collagen expression. Furthermore, there was a shift
away from pro-fibrotic/alternative pro-fibrotic macrophage signaling after LVAD
use. CONCLUSIONS: Despite robust cardiac unloading, capillary density and
fibrosis are unchanged compared with loaded hearts. Fibroblast-specific collagen
expression was decreased and might be due to decreased stretch and/or altered
macrophage polarization. Dysfunctional myocardium may persist, in part, from
ongoing inflammation and poor extracellular matrix remodeling. Understanding
these changes could lead to improved therapies for HF.
PMID- 28705317
TI - Myocardial Recovery After LVAD Implantation: A Vision or Simply an Illusion?
PMID- 28705319
TI - Connexin-45 as a New Gene Underlying Syndromic AV Block.
PMID- 28705318
TI - Progressive Atrial Conduction Defects Associated With Bone Malformation Caused by
a Connexin-45 Mutation.
AB - BACKGROUND: Inherited cardiac conduction disease is a rare bradyarrhythmia
associated with mutations in various genes that affect action potential
propagation. It is often characterized by isolated conduction disturbance of the
His-Purkinje system, but it is rarely described as a syndromic form. OBJECTIVES:
The authors sought to identify the genetic defect in families with a novel
bradyarrhythmia syndrome associated with bone malformation. METHODS: The authors
genetically screened 15 European cases with genotype-negative de novo
atrioventricular (AV) block and their parents by trio whole-exome sequencing,
plus 31 Japanese cases with genotype-negative familial AV block or sick sinus
syndrome by targeted exon sequencing of 457 susceptibility genes. Functional
consequences of the mutation were evaluated using an in vitro cell expression
system and in vivo knockout mice. RESULTS: The authors identified a connexin-45
(Cx45) mutation (p.R75H) in 2 unrelated families (a de novo French case and a 3
generation Japanese family) who presented with progressive AV block, which
resulted in atrial standstill without ventricular conduction abnormalities.
Affected individuals shared a common extracardiac phenotype: a brachyfacial
pattern, finger deformity, and dental dysplasia. Mutant Cx45 expressed in Neuro
2a cells showed normal hemichannel assembly and plaque formation. However,
Lucifer yellow dye transfer and gap junction conductance between cell pairs were
severely impaired, which suggested that mutant Cx45 impedes gap junction
communication in a dominant-negative manner. Tamoxifen-induced, cardiac-specific
Cx45 knockout mice showed sinus node dysfunction and atrial arrhythmia,
recapitulating the intra-atrial disturbance. CONCLUSIONS: Altogether, the authors
showed that Cx45 mutant p.R75H is responsible for a novel disease entity of
progressive atrial conduction system defects associated with craniofacial and
dentodigital malformation.
PMID- 28705320
TI - Quality and Equitable Health Care Gaps for Women: Attributions to Sex Differences
in Cardiovascular Medicine.
AB - The present review synthesizes evidence and discusses issues related to health
care quality and equity for women, including minority population subgroups. The
principle of "sameness" or women and men receiving equitable, high-quality care
is a near-term target, but optimal population health cannot be achieved without
consideration of the unique, gendered structural determinants of health and the
development of unique care pathways optimized for women. The aim of this review
is to promote enhanced awareness, develop critical thinking in sex and gender
science, and identify strategic pathways to improve the cardiovascular health of
women. Delineation of the components of high-quality health care, including a
women-specific research agenda, remains a vital part of strategic planning to
improve the lives of women at risk for or living with cardiovascular disease.
PMID- 28705322
TI - ACC International: An Overseas Perspective.
PMID- 28705321
TI - Implantable Hemodynamic Monitoring for Heart Failure Patients.
AB - Rates of heart failure hospitalization remain unacceptably high. Such
hospitalizations are associated with substantial patient, caregiver, and economic
costs. Randomized controlled trials of noninvasive telemedical systems have
failed to demonstrate reduced rates of hospitalization. The failure of these
technologies may be due to the limitations of the signals measured. Intracardiac
and pulmonary artery pressure-guided management has become a focus of
hospitalization reduction in heart failure. Early studies using implantable
hemodynamic monitors demonstrated the potential of pressure-based heart failure
management, whereas subsequent studies confirmed the clinical utility of this
approach. One large pivotal trial proved the safety and efficacy of pulmonary
artery pressure-guided heart failure management, showing a marked reduction in
heart failure hospitalizations in patients randomized to active pressure-guided
management. "Next-generation" implantable hemodynamic monitors are in
development, and novel approaches for the use of this data promise to expand the
use of pressure-guided heart failure management.
PMID- 28705323
TI - Refining Thromboembolic Risk in the General Population.
PMID- 28705324
TI - Bioprosthetic Total Artificial Heart Induces a Profile of Acquired
Hemocompatibility With Membranes Recellularization.
PMID- 28705325
TI - Hypertrophic Cardiomyopathy With Left Ventricular Apical Aneurysm.
PMID- 28705326
TI - Reply: Hypertrophic Cardiomyopathy With Left Ventricular Apical Aneurysm.
PMID- 28705327
TI - Reply: Chronic Kidney Disease Contributing to Dyspnea in Patients With Heart
Failure.
PMID- 28705328
TI - Chronic Kidney Disease Contributing to Dyspnea in Patients With Heart Failure.
PMID- 28705329
TI - Relationship between cone-beam CT technique and diagnostic usefulness in patients
undergoing embolotherapy for hepatocellular carcinoma.
AB - AIM: To determine the effect of different numbers of projection images in C-arm
cone-beam computed tomography (CBCT) on diagnostic content and image quality in
patients undergoing angiographic embolotherapy for hepatocellular carcinoma
(HCC). MATERIALS AND METHODS: A total of 29 patients who underwent contrast
enhanced conventional multidetector CT (MDCT) within 6 weeks prior to CBCT
acquired during embolotherapy for HCC between 2010 and 2013 were included in the
study. CBCT was acquired in each patient using a 5-s (248 projection images) or 8
s (396 projection images) protocol. Anonymised images were reviewed independently
by an interventional radiologist blinded to CBCT group. MDCT was used as a
reference to the patient's anatomy, and performance of CBCT was compared to that
of MDCT in each group. The level of concordance between CBCT and MDCT within each
group was assessed for the following variables: number of foci >1 cm, largest
tumour diameter, highest order branching vessel identified, image quality,
diagnostic quality, signal-to-noise ratio, and contrast-to-noise ratio (CNR).
CBCT radiation dose was recorded. RESULTS: There was no significant difference
between MDCT and CBCT within each group in the number of tumour foci >1 cm
identified or size of the largest focus measured. MDCT had superior image quality
compared to both CBCT groups (p<0.01), but CBCT demonstrated subsegmental
branches more often in each group than MDCT. Both CBCT groups demonstrated higher
CNR than MDCT (p<0.01). The dose-area product (3675+/-1295 versus 6598+/-1252
MUGy.m2; p<0.001) and skin dose (119+/-41 versus 212+/-38 mGy; p<0.001) were
significantly lower with 5-s CBCT than with 8-s CBCT. CONCLUSION: The
relationship between MDCT and CBCT in both groups was consistent. The information
obtained with 5-s CBCT was equivalent to that obtained with 8-s CBCT but with a
lower radiation dose.
PMID- 28705330
TI - Mucocoele-like lesions: is surgical excision still necessary?
AB - AIM: To assess the rate of upgrade in our screening population to determine
whether open excision biopsy of mucocoele-like lesions (MLL) is still required.
MATERIALS AND METHODS: A retrospective review of the breast screening database
from 1999-2014 was performed. RESULTS: MLL were identified on core biopsy in 113
women (0.6% of those recalled for a core biopsy). The majority (n=100, 88%) had a
localised cluster of calcification prompting screening recall. Eighty-seven
percent (n=99) underwent an excision biopsy; there was a 5% upgrade rate to
malignancy (all low/intermediate ductal carcinoma in situ [DCIS]) and 15 women
(15%) were found to have an additional "B3" lesion. Fourteen women did not
undergo excision biopsy; none of these women had a subsequent cancer at an
average of 5-years follow-up. Within the follow-up period, five additional
cancers were identified, one of these was in the ipsilateral breast and location,
albeit 9-years later. CONCLUSION: This is the largest study of MLL in the
literature to date. The present findings show a 5% upgrade rate to DCIS. As long
as the current management of low-risk DCIS remains surgical excision, the present
results support continued excision of MLLs, either surgically or by vacuum
assisted biopsy.
PMID- 28705331
TI - A non-interventional retrospective cohort study of the interaction between
methotrexate and proton pump inhibitors or aspirin.
AB - INTRODUCTION: Methotrexate (MTX) is an antifolate drug, which is frequently used
in the treatment of cancer. Proton pump inhibitors (PPIs) could delay the
elimination of plasma MTX in high-dose MTX therapy by inhibition of tubular
secretion, which could lead to MTX toxicity. However, the evidence of the
clinical relevance of this drug-drug interaction is inconsistent. No previous
studies into the effect of low dose aspirin on the elimination of MTX in high
dose therapy have been performed. Therefore, we evaluated the interaction between
MTX and PPIs or aspirin. METHODS: We conducted a non-interventional retrospective
cohort study in patients treated with high dose MTX (>=500mg/m2 or >1000mg),
between 2009 and 2016 at the OLVG ("Onze Lieve Vrouwe Gasthuis, Oost") in
Amsterdam, the Netherlands. Patients were included if MTX concentrations were
determined at 24, 48 or 72hours after high dose MTX treatment. We categorised the
cycles of high dose MTX therapy into delayed elimination or normal elimination.
Differences in patient characteristics and MTX dosing regimen were compared
between all groups by X2-test, Fisher's exact probability test or Mann-Whitney U
test. RESULTS: In total, 89 high dose MTX cycles were included. Delayed MTX
elimination was observed in 27 (30.3%) cycles. Co-administration of a PPI was
significantly more frequent in the delayed elimination group than in the normal
elimination group (P<0.001). There was no statistical effect observed by co
administration of aspirin. CONCLUSION: The use of PPIs during high dose MTX
treatment can lead to delayed MTX elimination. Discontinuation of PPIs during
high dose MTX treatment is recommended. Co-administration of aspirin did not
influence the elimination of MTX, but further research is needed.
PMID- 28705332
TI - Editorial Comment.
PMID- 28705333
TI - Interdisciplinarity in Norbert Wiener, a mathematician-philosopher of our time.
AB - The paper focuses on interdisciplinarity in Norbert Wiener looking at his
scientific work from a unitary point of view. It begins with a bird's-eye view of
the history of the term "interdisciplinarity", pointing out how the word was the
result of a movement of ideas that took place in US science along the whole
Twentieth century. This way, the Wiener's conceptions and practices concerning
interdisciplinarity are compared with their historical context, showing analogies
and peculiarities. For Wiener, interdisciplinary research by very small groups
whose members have a very broad interdisciplinary basis is an essential
prerequisite for new fundamental ideas for invention and discoveries. On the
contrary, in his opinion, mass attacks by large well financed interdisciplinary
research groups with a big number of overspecialized member is useful only in a
second phase in which invention and discoveries need to be implemented by
designers and developers. Finally, through a conceptual matching between Wiener's
ideas and the ones of Jose Ortega y Gasset, it appears how the Wienerian small
interdisciplinary group would fit better with the Kuhnian revolutionary phase in
science, while the big interdisciplinary group would fit better to the Kuhnian
normal science.
PMID- 28705334
TI - New normal: From basic to clinical medicine.
PMID- 28705335
TI - [Inauguration of the 51th congress of the French College of Vascular disease,
Wednesday March 15, 2017].
PMID- 28705336
TI - [Cardiovascular health in women: Effective prevention requires teamwork].
PMID- 28705337
TI - [Treatment of post-catheterization pseudoaneurysms by ultrasound-guided thrombin
injection: A single-center experience and practical guideline].
AB - Ultrasound-guided thrombin injection has been shown to be a safe and effective
treatment for iatrogenic post-catheterization pseudoaneurysms, but still is
underused in France. We report our single-center experience and propose a
technical guideline for ultrasound-guided thrombin injection. Ultrasound-guided
thrombin injection should be considered to be the first-line treatment of
iatrogenic pseudoaneurysms.
PMID- 28705338
TI - [Femoropopliteal angioplasty: Short- and mid-term results].
AB - BACKGROUND: Percutaneous endovascular therapy is becoming a primary option for
managing femoropopliteal occlusive disease. The purpose of this study was to
evaluate the mid-term results of endovascular treatment of femoropopliteal
arterial disease. METHODS: Femoropopliteal percutaneous transluminal angioplasty
was performed on 162 consecutive limbs (160 patients) from January 2006 to
January 2016. RESULTS: In our study, 87.6% of patients had critical limb
ischemia. Lesions were classified as Trans-Atlantic Inter-Society Consensus
(TASC) A (43%), B (43%), C (7%), and D (7%). Femoropopliteal interventions
included angioplasty only in 70 cases (43.2%), and the remaining 92 (56.8%)
received at least one stent. Technical success was achieved in 98.7% of patients,
with three deaths and a major morbidity rate of 15%. The actuarial primary
patency at 12 and 36 month was 65.4% and 40.2%, respectively, 33 peripheral
reinterventions were performed after femoropopliteal axis occlusion, resulting in
an actuarial primary limb preservation rate of 94.4 at 12 months. Comparison
between angioplasty only and the use of stent show no difference in primary
patency (P=0.832) and limb salvage (P=0.67). Negative predictors of primary
patency determined by univariate analysis included popliteal location (P<0.001)
and TASC D (P<0.001). However, diabetes mellitus (P=0.001) and poor run off
(P<0.001) were the principal predictive factors of limb loss. CONCLUSION:
Femoropopliteal angioplasty can be performed with a low morbidity and mortality.
Intermediate primary patency is directly related to TASC classification and
popliteal localization.
PMID- 28705339
TI - [Surgical and endoluminal management of the inflammatory aortitis: A Tunisian
center experience].
AB - Non-infectious aortitis is usually due to giant-cell arteritis, Takayasu disease
or Behcet disease. The main aortic lesions are stenoses, occlusions and aneurysms
in the Takayasu disease and aneurysms in the Behcet disease and giant-cell
arteritis. Treatment is based on corticosteroid therapy and surgery. Endoluminal
management is now the rule. We report a retrospective descriptive study of 10
patients who underwent surgical or endoluminal management of inflammatory lesions
of the aorta between January 2000 and December 2015. There were 4 cases of
Takayasu disease and 6 cases of Behcet disease. The aortic lesions were
aneurysmal in all of the patients with Behcet disease. In the patients with
Takayasu disease, aortic occlusions predominated, associated with other arterial
lesions. Four patients with Behcet disease were managed surgically, and 2
patients underwent endovascular repair. All of the patients with Takayasu disease
underwent surgery. Two patients died in the postoperative period, and two
patients died during long-term follow-up. Systematic screening, as well as
regular monitoring of the entire aorta during the follow-up, is necessary due to
the frequency of aortic aneurysms.
PMID- 28705340
TI - [Factors of compliance with the wearing of elastic compression stockings in a Sub
Saharan population].
AB - INTRODUCTION: Elastic venous compression is the basic treatment of chronic venous
insufficiency (CVI) and deep vein thrombosis (DVT). Very little data exist in sub
Saharan Africa concerning the wearing of compression stockings. AIM: To determine
the factors of compliance with wearing elastic compression stockings. MATERIALS
AND METHODS: This retrospective cross-sectional descriptive and analytical study
involved 200 consecutive patients (93 cases of DVT, 94 cases of CVI, 13 cases of
DVT and CVI). Data on compliance with wearing compression stockings and the
factors influencing this compliance were collected. RESULTS: The average age was
51+/-15 years old (range 17 and 91 years old). The sex ratio was 1. The majority
of patients (78.5%) performed their occupation in a standing position, for more
than 8hours per day for 80.5%. DVT were preferentially on the left side (52.9%)
and proximal (44.4%). Concerning the CVI, the predominant symptoms were class C3
(52.3%), C4 and C5 (43.9%) of the CEAP classification. Bilateral involvement was
dominant (53.3%) and the large saphenous vein was the most affected (66.9%)
compared with 33.1% for the small saphenous vein exclusively. The most common
type of stockings prescribed was the lower mid-thighs (57%), followed by the
pantyhose (30%), in classes 3 (63%) and 2 (36.5%). The majority of patients (75%)
agreed to wear their stockings after prescription with a good compliance rate of
58.5% at the beginning of the prescription. At the time of the study, this rate
was 11%. The optimal duration of compliance with wearing compression stockings
was 6 months (64%). Over 12 months this rate fell to 7.5%. The main causes were
stocking-related compression discomfort (36.7%), patient neglect (21.5%),
threading difficulties (16.9%), and an unfavorable working environment (8.7%).
The determining factors of compliance with wearing of stockings were living in a
couple (68.4% vs 54.2, P=0.04), CVI (53% vs 38.2%, P=0.04) and C3 (39% vs 80%),
C4 (37.5% vs 17%), C5 (18% vs 3%) CVI (P=0.0005). CONCLUSION: Compliance with
wearing elastic compression stockings is mediocre. The main factors of non
compliance are discomfort, threading difficulties and patient neglect.
PMID- 28705341
TI - [Is ultrasound guidance contributive to vascular access in endovascular therapy?]
AB - OBJECTIVES: The aim of this study was to evaluate the contribution of ultrasound
guidance (UG) to vascular puncture in endovascular therapy. Ultrasound guidance
was evaluated by comparison with the rates of failures and complications of the
traditional techniques of percutaneous vascular access. MATERIALS AND METHODS: We
reviewed all the consecutive percutaneous revascularizations (percutaneous
transluminal angioplasty and/or stenting, treatment of aneurysms and vascular
traumatisms) since the standardization of the systems of closing (extra- and
endovascular). The UG began in November 2011. The main objectives of the
evaluation were the rate of failure of the punctures and the rate of
complications (hematoma requiring transfusion or surgery for hemostasis, false
aneurysm, dissection, thrombosis, infection). The failures and the complications
were compared between two groups UG- and UG+. RESULTS: Between January 2008 and
December 2014, 841 punctures were carried out by femoral route (85%), brachial
route (12%), popliteal route (1%), axillary route (0.5%), and posterior tibial
route (0.5%) with introducers between 4F and 12F. There were 20 complications
(2.3%): six hematomas, four pseudo-aneurysms, three thromboses, one nervous
paralysis, one stent infection, and seven percutaneous failures. The
complications and the failures were significantly lower with ultrasound guidance
(0.9% vs. 3.6%; P=0.02, and 0.2% vs. 1.4%; P=0.01, respectively). CONCLUSION:
Ultrasound guidance makes it possible to significantly decrease the rate of
complications and failures of the percutaneous accesses. This tool allowed a
clear increase in the realization of the percutaneous angioplasties in outpatient
hospitalization.
PMID- 28705342
TI - Unruptured multiple intracranial aneurysms associated with Behcet's disease.
AB - Behcet's disease is a systemic inflammatory disorder with a wide variety of
cardiovascular complications. Intracranial aneurysm is extremely rare. Herein, we
are presenting a 41-year-old male with Behcet's disease and a headache. A cranial
computed tomography scan angiography showed unruptured right supra cavernus
internal carotid aneurysm and right sylvian artery aneurysm. Treatment consisted
of prednisone and azathioprine. Control imaging showed no aneurysm.
PMID- 28705343
TI - [Recanalization procedure of the common femoral vein following iatrogenic femoral
chronic occlusion: 3 cases].
AB - : Common femoral vein occlusion (CFVO) is frequently found in patients with
chronic venous insufficiency. The iatrogenic form, secondary to either central
catheter or surgery, is very rare but highly symptomatic. Classical compression
therapy barely improves the clinical status of these patients, making them
suitable candidates for an interventional procedure for venous recanalization.
METHODS: We report here three consecutive cases of iatrogenic CFVO referred to
our outpatient clinic because the disease had an impact on daily life activities.
We detail the recanalization procedure, the Doppler control and the short-term
outcome. RESULTS: In each case, endovascular recanalization required rigid
material (rigid guide or Colapinto needle) to cross the fibrous adhesions before
angioplasty could be performed with stenting. The procedure required two attempts
in each case, underlining its complexity, but eventually enabled effective
recanalization. No major complication occurred per- or post-procedure. One month
later, a duplex Doppler control confirmed the permeability of the common femoral
vein. The patients had experienced rapid and significant symptom improvement.
CONCLUSION: Patients suffering from severe chronic venous insufficiency caused by
iatrogenic CFVO can benefit from endovascular recanalization. Although these
procedures may be complex due to the extensive fibrosis at the Scarpa and require
specialized equipment, no major complications were observed. Patency of the
recanalization persisted at least one month after the procedure. Symptom relief
was good.
PMID- 28705344
TI - [Claude Bernard-Horner syndrome revealing spontaneous aneurysm of the vertebral
artery].
AB - False aneurysms of the extracranial vertebral artery (FAVA) are rare because of
the path of the artery at the level of the transverse holes. They can be
secondary to penetrating cervical trauma, spontaneous in the course of an
angiopathy such as Ehlers-Danlos syndrome, or iatrogenic. We report the case of a
31-year-old woman who presented a syndrome of Claude Bernard-Horner related to a
spontaneous FAVA. The angioscanner confirmed the diagnosis and the patient
underwent successful surgical treatment of the false aneurysm with ligature of
the vertebral artery. Outcome was favorable.
PMID- 28705345
TI - [Multiple abdominal venous aneurysms revealed by pulmonary embolism].
AB - Venous aneurysms are rare lesions, they have been reported in most venous
territories. Abdominal location is unusual. A 61-year-old man presented with
chest pain and dyspnea attributed to pulmonary embolism. Computed tomography of
the abdomen showed multiple thrombosed venous aneurysms of the left external
iliac vein and the inferior vena cava. There were no signs of rupture. The
patient received anticoagulant treatment. He had no surgical treatment.
PMID- 28705346
TI - Efficient Generation of Dopamine Neurons by Synthetic Transcription Factor mRNAs.
AB - Generation of functional dopamine (DA) neurons is an essential step for the
development of effective cell therapy for Parkinson's disease (PD). The
generation of DA neurons can be accomplished by overexpression of DA-inducible
genes using virus- or DNA-based gene delivery methods. However, these gene
delivery methods often cause chromosomal anomalies. In contrast, mRNA-based gene
delivery avoids this problem and therefore is considered safe to use in the
development of cell-based therapy. Thus, we used mRNA-based gene delivery method
to generate safe DA neurons. In this study, we generated transformation-free DA
neurons by transfection of mRNA encoding DA-inducible genes Nurr1 and FoxA2. The
delivery of mRNA encoding dopaminergic fate inducing genes proved sufficient to
induce naive rat forebrain precursor cells to differentiate into neurons
exhibiting the biochemical, electrophysiological, and functional properties of DA
neurons in vitro. Additionally, the generation efficiency of DA neurons was
improved by the addition of small molecules, db-cAMP, and the adjustment of
transfection timing. The successful generation of DA neurons using an mRNA-based
method offers the possibility of developing clinical-grade cell sources for
neuronal cell replacement treatment for PD.
PMID- 28705347
TI - Loss of BAP1 expression is very rare in breast carcinoma.
PMID- 28705348
TI - 'Aussie Normals': an a priori study to develop reference intervals in a healthy
Australian population using the Beckman Coulter LH 750 Haematology Analyser as
candidates for harmonised values.
AB - Reference limits or intervals are important benchmarks or tools that help the
clinician to distinguish between a result that is most likely to lie within a
'healthy' or diseased category. It has been suggested that a review of
haematology reference intervals is long overdue. In this study we report on our
findings for analytes routinely measured in a complete blood count (CBC)
performed on the Beckman Coulter LH 750 analyser and an additional comparative
study using the Beckman Coulter LH 750, the Sysmex XN and Abbott Sapphire. The
results from the comparative study indicate that bias would not prevent
harmonisation of reference intervals for these common haematology parameters. The
results offered by the Aussie Normals study represent good candidates as the
basis for harmonisation reference intervals.
PMID- 28705349
TI - Cumulative advantage in collective action groups: How competition for group
members alters the provision of public goods.
AB - Research on collective action problems and the provision of public goods has
yielded an array of important insights into why people sacrifice for their
groups, but ignores the processes that bring people into those groups in the
first place. The literature is also silent on the fact that groups providing
similar public goods often compete with one another to attract new members. We
extend the reach of theories of collective action problems to bring them to bear
on these interrelated issues. Results from four experiments support our
predictions about when group members compete to attract new adherents by
sacrificing more for group goals. Further, we find that prospective members join
more productive groups at much higher rates and then contribute to them at high
levels. These processes give way to cumulative advantage, whereby initially
productive groups continually attract new members. Thus competition for members
can yield large inequalities in the size and success of collective action groups.
PMID- 28705350
TI - Trajectories of relationship supportiveness after childbirth: Does marriage
matter?
AB - Relationship quality for married couples typically declines after the birth of a
(first) child, as parenthood brings new identities, stresses, and
responsibilities for mothers and fathers. Yet, it is less clear whether
nonmarital relationship quality follows a similar trajectory, particularly given
the greater selectivity of nonmarital relationships that persist over time. This
paper uses data from the Fragile Families and Child Wellbeing Study (N = 3,459)
with latent growth curve models to examine relationship quality (measured by
mothers' perceived supportiveness about fathers) for married and unmarried
couples over nine years after a child's birth. Findings suggest that marriage at
birth is protective for relationship supportiveness over time, net of various
individual characteristics associated with marriage, compared to all unmarried
couples at birth; however, marriage does not differentiate supportiveness
compared to the subset of unmarried couples who remain stably together. Also,
unmarried couples who get married after the birth have more supportive
relationships compared to all unmarried couples who do not marry-though less so
when compared to couples who remain stably together.
PMID- 28705351
TI - Housework share between partners: Experimental evidence on gender-specific
preferences.
AB - This paper uses a novel vignette-based experimental design to investigate the
reasons underlying the gendered division of housework. We are particularly
interested in the role of gender-specific preferences: are there differences in
the utility that men and women derive from housework, and might these be
responsible for the fact that women continue to do more housework than men? It is
difficult to address these questions with conventional survey data, because of
inherent problems with endogeneity and ex-post rationalization; our experimental
design circumvents these problems. We find remarkably little evidence of any
systematic gender differences in preferences, and a general inclination towards
an equal distribution of housework; this suggests that the reasons for the
gendered division of housework do not derive from gender differences in
preferences, and must lie elsewhere.
PMID- 28705352
TI - Gender differences in the earnings produced by a middle range education: The case
of Canadian 'colleges'.
AB - In this paper we use data on consecutive cohorts of recent graduates from
community colleges or community college-like institutions to address the
following questions about the gender earnings gap: i) What was the trend in the
gender earnings gap for these recent graduates? ii) What role in the observed
trends in the gender earnings gap was played by occupational demand? iii) How and
to what extent did the domestic division of labour contribute to the gender
earnings gap in this young sample? We find that the gap fell then rose, that
occupational demand played a role in these shifts, and that the domestic division
of labour did indeed contribute to the gap in this young sample. Furthermore, our
results point to a process of cumulation of factors that increase the earnings
gap which has both substantive and methodological implications.
PMID- 28705353
TI - The earnings payoff from attending a selective college.
AB - Studies relating the selectivity of colleges to the earnings of their graduates
report inconsistent findings. Some find no effects; most report statistically
significant but quite small earnings benefits from attending a more selective
college; and a few studies report large effects. Analyzing two recent national
longitudinal studies of college graduates, with models sensitive to selection
bias, we find large earnings payoffs from attending a highly selective college
both four and ten years after graduation. However, those returns are uneven: full
time working women graduates earn a lot less than their male counterparts from
equivalent colleges, college majors pay differently, and family background also
affects earnings over and above one's college's selectivity. Nevertheless,
earnings differences attributable to college selectivity are striking.
PMID- 28705354
TI - If they think I can: Teacher bias and youth of color expectations and
achievement.
PMID- 28705355
TI - Growing educational differentials in the retreat from marriage among Korean men.
AB - Applying discrete-time hazard models to person-year data constructed from 1%
microdata sample of 2010 Korean Census, we explore how men's education affects
their transition to first marriage, and how the relationship between education
and marriage has changed across three 10-year birth cohorts of Korean men born
from 1946 to 1975. Drawing on Oppenheimer's theory of marriage and review of
changing educational and economic contexts of Korean men, we develop a hypothesis
on growing educational differentials in marriage. We find that the high educated
delay marriage until later ages but catch up to the extent to which they are
eventually more likely to marry than the low educated. There is a continued trend
across cohorts toward the delay and avoidance of marriage at all educational
levels. However, the trend of retreat from marriage has been more substantial for
men with high school or less education compared to men with a university degree,
leading to growing educational gaps over time in marriage. Among the three
cohorts, the youngest cohort, among which low educated men's economic prospects
have particularly deteriorated due to rapid educational expansion and economic
crisis, shows most pronounced decline in marriage.
PMID- 28705356
TI - Preference effects on friendship choice: Evidence from an online field
experiment.
AB - Observed friendship choices are constrained by social structures and thus
problematic indicators for underlying personal preferences. In this paper, we
report on a study demonstrating the causal effects of preference in friendship
choice based on an online field experiment. Specifically, we tested two important
forces that govern friendship choices: preference for shared group identity
(operationalized as the desire to befriend others sharing the same place-of
origin identity) and preference for high status (operationalized as the desire to
befriend others from high-status institutions). Using an online field experiment
in one of the largest social network service websites in China, we investigated
the causal preference effects of these two forces free from structural
constraints. The results of our study confirm the preference effects on
friendship choice in both of the two dimensions we tested.
PMID- 28705357
TI - Trajectories of neighborhood attainment after prison.
AB - A potentially important but understudied aspect of prisoner reentry is the
neighborhood environments experienced by formerly incarcerated people. We know
that many formerly incarcerated people return to very disadvantaged neighborhood
environments and that returning to disadvantaged neighborhoods after prison
increases the risk of recidivism and reduces employment. Yet very little is known
about the social, economic, and institutional processes that sort formerly
incarcerated people into different neighborhoods after release or their
trajectories of neighborhood attainment over time. Motivated by a
conceptualization of prisoner reentry and reintegration as a process that unfolds
over time, we examine trajectories of neighborhood environments after release.
Motivated by the literature on neighborhood attainment, social capital, and the
role of criminal justice institutions in structuring the lives of former
prisoners, we examine sources of variation in neighborhood attainment. We use
administrative data from the Michigan Department of Corrections on formerly
incarcerated people paroled in 2003 and followed for two years after release.
Descriptive results from a latent class trajectory model show that most white and
black formerly incarcerated people experience flat trajectories, with little
upward or downward residential mobility over time. Findings from multi-level
growth curve models suggest that institutional factors are particularly important
for the neighborhood attainment of whites, while human capital and social ties
are particularly important for blacks. Among both blacks and whites, pre-prison
and first post-prison neighborhood conditions exhibit a strong association with
post-prison neighborhood attainment, although these associations are larger for
blacks than whites.
PMID- 28705358
TI - The status value of age.
AB - A controlled experiment and three replications examined the relationship between
a person's age as a status characteristic and the value placed on that person as
a potential group member. The experiments used computer-generated avatars to
isolate the effects of age on the status value of partners being chosen for a
work-related task. The design allowed us to compare the effect of age on status
for members of three distinct groups: younger adults, middle-aged adults, and
much older adults. Results showed that undergraduate participants rated middle
aged adult avatars higher on status indicators and chose to work with middle-aged
adult avatars significantly more often than younger adult or much older adult
avatars. The participants rated the much older avatar higher on most indicators
of status than the younger adult avatar. They also chose to work with a much
older adult more often than a person closer to their own age. This sample of
undergraduate students placed the most value on the potential contributions of a
middle-aged adult compared to a younger adult and also to a much older adult,
suggesting that age as a status characteristic has more than two relevant
categories, younger versus older. Further research is needed to determine whether
the status value of age rises to a peak in middle age and declines thereafter.
PMID- 28705359
TI - Misconceived equity? Health care resources, contextual poverty, and child health
disparities in Peru.
AB - Although many studies have examined determinants of child health, fewer have
explored factors explaining regional disparities in child health outcomes. In the
Peruvian context, we examined the relationship between regional disparities in
child malnutrition and local variation in health resources (health care resources
and the socioeconomic environment). Using the Peruvian 2007-2008 Continuous
Demographic and Health Survey (N = 8020) and governmental administrative data,
our analyses show that 1) only selected types of health care resources (medical
professionals and outpatient visits) are related to child nutritional status, 2)
local poverty predicts nutritional status net of household characteristics, and,
most importantly, 3) a significant portion of regional differences in child
malnutrition are explained by local poverty, whereas health care resources are
not associated with regional disparities. These findings suggest that the local
socioeconomic environment is a key determinant of both child health outcomes and
regional disparities in these outcomes.
PMID- 28705360
TI - Do inferences of competence from faces predict political selection in
authoritarian regimes? Evidence from China.
AB - Candidate appearance is a significant predictor of election outcomes in
democracies because voters often make inference of competence based on facial
appearance. Do inferences of competence from faces matter in autocracies? In this
article, we study the effects of candidate appearance on the selection of three
types of Chinese officials: (1) rural deputies elected to a local people's
congress (LPC), (2) urban deputies elected to the LPC, and (3) unelected mayors
and bureaucrats. We find that facial competence cues are relevant only to the
votes received by rural LPC candidates. Our findings suggest the importance of
information accessibility in political selection. In particular, the
"selectorate" of mayors and bureaucrats do not need facial appearance cues
because they have access to substantive information about the quality of
political candidates. Our findings provide a possible explanation for the
resilience of some autocracies: they are able to identify talent through an
informative, albeit non-electoral, selection mechanism.
PMID- 28705361
TI - Changing perceived importance of religion in mainland China, 1990-2012: An age
period- cohort analysis.
AB - The comprehensive social reform and relaxation of religious regulation in
mainland China have encouraged scholars to propose a revival thesis of religion,
predicting a rising prevalence of religious adherence in the Reform Era. This
study extends the revival thesis by focusing attention on people's subjective
religiosity, and investigates age, period, and cohort effects on the transition
in perceived importance of religion from 1990 to 2012. Capitalizing on the
repeated cross-sectional data of the China sample in the World Values Survey,
this study shows that (1) The senior population, relative to the younger
counterpart, attaches greater importance to religion. (2) The net period effect
suggests that Chinese citizens' perceived importance of religion follows an
upward trend by the early 2000s, but no significant growth is detected
henceforward. (3) The cohorts who experienced the anti-religion Mao's Era in
their adolescent life course stage have an evidently lower probability of viewing
religion to be important, in relation to the cohorts of the Reform Era.
Theoretical implications of the empirical age-period-cohort patterns for the
religious economies theory and change of Chinese religious landscape are
discussed.
PMID- 28705362
TI - Racial double standards and applicant selection.
AB - Using double standards to judge job applicants can prevent the selection of
qualified candidates who possess disadvantaged status characteristics.
Experimental studies have shown that when assessors compare equally qualified
women and men for jobs, the men are more likely to be recommended for hiring. We
propose that the theoretical processes affecting choices by gender also will
apply with candidates differentiated by race. We test that and other predictions
using a modification of the application folders design used in double standards
research. We found that double standards affected job recommendations and judged
suitability of candidates, but not their judged competence. We believe that the
process operates outside of conscious choice of candidates, and we used that
insight to test an intervention to overcome using double standards in situations
of race-differentiated candidates.
PMID- 28705363
TI - Black people don't exercise in my neighborhood: Perceived racial composition and
leisure-time physical activity among middle class blacks and whites.
AB - Using a sample of middle class blacks and whites living in urban and suburban
areas, this article focuses on how perceptions of the racial composition of
neighborhoods influence leisure-time physical activity. Using an ordinal
representation of an underlying continuous indication of the perceived percentage
of blacks and whites within an egocentric neighborhood, the results show that
black men are significantly less likely to be physically active in neighborhoods
perceived as predominately white. Alternatively, they are more likely to be
physically active in neighborhoods perceived as racially diverse and
predominately black. Conversely, for black women, white women, and white men,
physical activity increases as the perception of one's neighborhood becomes
increasingly white. Black women are significantly less likely to engage in
physical activity in neighborhoods perceived as predominately black and urban.
Drawing upon the intersectionality framework, I discuss how perceptions of
criminalization and safety lead to different levels of leisure-time physical
activity for middle class black women and men relative to their white middle
class counterparts.
PMID- 28705364
TI - Political democracy, economic liberalization, and macro-sociological models of
intergenerational mobility.
AB - Building on the previously investigated macro-sociological models which analyze
the consequences of economic development, income inequality, and international
migration on social mobility, this article studies the specific contextual
covariates of intergenerational reproduction of occupational status in post
communist societies. It is theorized that social mobility is higher in societies
with democratic political regimes and less liberalized economies. The outlined
hypotheses are tested by using micro- and macro-level datasets for 21 post
communist societies which are fitted into multilevel mixed-effects linear
regressions. The derived findings suggest that factors specific to transition
societies, conventional macro-level variables, and the legacy of the Soviet Union
explain variation in intergenerational social mobility, but the results vary
depending which birth cohorts survey participants belong to and whether or not
they stem from advantaged or disadvantaged social origins. These findings are
robust to various alternative data, sample, and method specifications.
PMID- 28705365
TI - Gender quotas for women in national politics: A comparative analysis across
development thresholds.
AB - Women's share of global lower or single house parliamentary seats has increased
by over 70% over the course of the 21st century. Yet these increases have not
been uniform across countries. Rather countries with low levels of socioeconomic
development have outpaced developed democracies in terms of the gains made in the
formal political representation of women. One reasonable explanation for this
trend is the adoption in many poorer countries of national gender quota
legislation, that is, affirmative action laws intended to compensate for sex
discrimination in the electoral process. Yet, cross-national analyses examining
quotas as an explanatory factor typically use a simple binary (yes/no) variable
that either conflates the diverse intra-quota variations into a single variable
or includes only one part of the many quota variations. By contrast, using an
originally compiled dataset that includes 167 countries from 1992 to 2012, this
paper employs measures of gender quota legislation that capture the complexity
and considerable diversity of existing quota legislation. These measures allow us
to identify the specific factors that have helped so many less developed
countries rise to the top of international rankings in recent years. The findings
indicate that the effect of each type of gender quota, as well as other
explanatory variables, do not operate in the same way across all countries.
Specifically, voluntary political party quotas are substantially more effective
in developed countries, while reserved seat quotas are only significant in least
developed countries. Electoral candidate quotas, on the other hand, can be
significant across all countries, however only have a positive effect when they
are accompanied by placement mandates that ensure women are placed in winnable
positions, sanctions for non-compliance that are significant enough to force
adherence, and a minimum mandated threshold of at least 30%.
PMID- 28705366
TI - Letter From the Guest Editor: Pelvic Magnetic Resonance Imaging.
PMID- 28705367
TI - Dynamic Magnetic Resonance Imaging of the Pelvic Floor.
AB - Pelvic floor dysfunction is a widespread condition affecting up to 50% of elderly
women. It markedly compromises the quality of life owing to various disabling
symptoms such as pelvic pain, pelvic organ prolapse, and urinary and fecal
incontinence. Although age and female sex are the main risk factors, others
include multiparity, obesity, and connective tissue disorders. Pelvic floor
dysfunction is frequently multicompartmental, and failure to diagnose it
accurately often leads to treatment failure. Dynamic pelvic floor magnetic
resonance imaging is a robust tool that enables simultaneous visualization of the
3 pelvic floor compartments and is indispensable for precise preoperative
evaluation.
PMID- 28705368
TI - Imaging of Pelvic Floor Reconstruction.
AB - Stress urinary incontinence and pelvic organ prolapse are 2 common pelvic floor
disorders that are important causes of pelvic pain and disability. Mesh and sling
placement are some of the surgical treatment options available for treatment of
these conditions. In addition to clinical assessment, imaging plays an important
role in managing postoperative patients with complications such as recurrent
organ prolapse and chronic pain. Role of high-resolution pelvic magnetic
resonance imaging with additional advanced imaging techniques, such as magnetic
resonance neurography that are invaluable in managing such patients, are
discussed in this article.
PMID- 28705369
TI - Magnetic Resonance Imaging of Pelvic Masses: A Compartmental Approach.
AB - Magnetic resonance imaging (MRI) is often "one stop shop" for evaluating female
pelvic masses that helps in diagnosis, staging, and restaging of these tumors. A
pelvic mass can arise from any tissue present within the pelvis. Although most
masses in the female pelvis arise from the reproductive organs, masses may also
arise from the gastrointestinal tract, urinary system, adjacent soft tissues,
peritoneum, etc. It may not always be possible to determine the site of origin or
distinguish these masses based on imaging characteristics. However, familiarity
with the clinicopathologic and MRI features of most common pelvic masses helps in
narrowing the differential diagnosis. Diagnosis of these masses needs a holistic
approach as required for any tumor including clinical history, laboratory data,
and imaging characteristics. We focus on MRI characteristics of commonly
encountered pelvic masses. A compartmental imaging approach is discussed in this
article that helps in identifying and characterizing these masses.
PMID- 28705370
TI - Magnetic Resonance Imaging of Gynecological Malignancies: Role in Personalized
Management.
AB - Gynecological malignancies are a leading cause of mortality and morbidity in
women and pose a significant health problem around the world. Currently used
staging systems for management of gynecological malignancies have unresolved
issues, the most important being recommendations on the use of imaging. Although
not mandatory as per the International Federation of Gynecology and Obstetrics
recommendations, preoperative cross-sectional imaging is strongly recommended for
adequate and optimal management of patients with gynecological malignancies.
Standardized disease-specific magnetic resonance imaging protocols help assess
disease spread accurately and avoid pitfalls. Multiparametric imaging holds
promise as a roadmap to personalized management in gynecological malignancies. In
this review, we will highlight the role of magnetic resonance imaging in
cervical, endometrial, and ovarian carcinomas.
PMID- 28705371
TI - Magnetic Resonance Neurography of the Pelvic Nerves.
AB - Chronic pelvic pain syndrome is commonly caused by nerve injury, inflammation, or
entrapment. Owing to the complex anatomy and branching patterns of pelvic nerves,
pelvic neuropathies are often difficult to illustrate and diagnose. High
resolution 3-T magnetic resonance neurography is a promising technique for the
evaluation of peripheral neuropathy. In this article, the authors discuss the
normal anatomy of major pelvic nerves, technical considerations of high
resolution imaging, and normal and abnormal imaging appearances with relevant
case examples.
PMID- 28705372
TI - Cross-Sectional Imaging for Inflammatory Arthropathy of the Pelvis.
AB - Inflammatory arthropathy predominantly affecting the axial skeleton can cause
pain, stiffness, disability, and ankylosis. This article discusses the use of
cross-sectional imaging in the domain of inflammatory pelvic and axial
arthropathy highlighting the key distinguishing features of common known diseases
and their differential diagnoses.
PMID- 28705373
TI - Magnetic Resonance Imaging of Nonneoplastic Musculoskeletal Pathologies in the
Pelvis.
AB - Musculoskeletal pathologies in the pelvis encompass a wide variety of lesions
including femoroacetabular impingement, athletic pubalgia, ischiofemoral
impingement, and apophyseal avulsion injuries. Magnetic resonance imaging is the
noninvasive imaging modality of choice for the diagnosis and management of these
lesions. In this article, the authors discuss the nonneoplastic musculoskeletal
lesions in the pelvis, with illustrations and relevant case examples.
PMID- 28705374
TI - [Relevance of the socioeconomic and health context in patient satisfaction].
AB - OBJECTIVE: To determine which factors of the socioeconomic and health contexts
influence the perception of the satisfaction of the population with the health
services. METHODS: The data come from the European Health Survey of 2009. In the
22,188 subjects surveyed, the relationship between the perception of satisfaction
with the health services received and the individual and contextual variables was
studied, applying a multilevel analysis. RESULTS: The factors of the
socioeconomic and health contexts that influence satisfaction are: higher rates
of low level of studies where the perception of excellence is less likely (odds
ratio [OR]: 0.48-0.82) and dissatisfaction is more prevalent (OR: 1.46-1.63).
Likewise, the proportion of unsatisfied citizens is lower when per capita
expenditure on health services is very high (>1400 ?) (OR: 0.49-0.87) and the
ratio "primary health care physicians/inhabitants" is high (>60) (OR: 0.500.85).
In addition, the prevalence of dissatisfaction describes a positive linear trend
with the unemployment rate (OR: 1.12; p=0.0001) and the relative magnitude of the
services sector (OR: 1.03; p=0.001). By contrast, this linear trend is negative
as the Health Care Coverage Ratio increases (OR: 0.88; p=0.04). CONCLUSIONS: The
individual factors that determine patient satisfaction are: sex, age, mental
health and country of birth. In addition, there are differences in patient
satisfaction among the autonomous communities according to socio-economic
determinants such as GDP per capita, low-level study rates, unemployment rates or
number of inhabitants/doctor's ratio. User satisfaction studies as well as being
adjusted for individual variables such as sex, age or health level should also
take into account characteristics of the socioeconomic environment of the
geographic area where they reside.
PMID- 28705375
TI - Regulation of expression and trafficking of perforin-2 by LPS and TNF-alpha.
AB - Perforin-2 is constitutively expressed in macrophages that are required for
bacterial control. In this study, we found that perforin-2 is expressed in human
macrophages with two isoforms: full-length perforin-2a and a splice variant,
perforin-2b. Two isoforms show different subcellular distributions. Perforin-2a
was predominantly localized to the membrane of endosome-like vesicles by a C
terminal transmembrane domain. In contrast, the short isoform perforin-2b lacking
the transmembrane domain failed to localize to the membrane of vesicles.
Furthermore, we determined that the pro-inflammatory stimuli LPS and TNF-alpha
induced perforin-2a expression via the NF-kappaB pathway and triggered perforin
2a vesicles fusion with lysosomes. On the other hand, we detected the secretion
of perforin-2b in response to LPS stimulation. Taken together, our data provide
the evidence that membrane-bound and secretory isoforms of perforin-2 are present
in human macrophages and may play important roles in immune defense.
PMID- 28705376
TI - Regional Variation in Mortality, Length of Stay, Cost, and Discharge Disposition
Among Patients Admitted for Heart Failure in the United States.
AB - The objective of the study was to provide contemporary evidence on regional
variation in hospitalization outcomes in patients with heart failure (HF) in the
United States. Using the National Inpatient Sample, we compared hospitalization
outcomes among primary HF admissions (2013 to 2014) among the 4 Census regions of
the United States. Overall, an estimated 1.9 million HF hospitalizations occurred
in the United States over the study period. Mortality rate was 3%, the mean
length of stay was 5.3 days, the median cost of hospitalization was US$7,248, and
the rate of routine home discharge was 51%. There was a significant regional
variation for all end points (p <0.001); for example, compared with other regions
of the country, the risk-adjusted rate of in-hospital mortality was highest in
the Northeast (3.2%) and lowest in the Midwest (2.7%); and within each region,
these mortalities were higher in the rural locations (range: 3.0% to 3.8%) than
in the urban locations (range: 2.7% to 3.1%). In addition, the Northeast region
had the longest length of stay (mean: 5.9 days) and the lowest risk-adjusted rate
of routine home discharge (42%). However, the cost of hospitalization was highest
in the West (median: US$8,898) and lowest in the South (US$6,366). A similar
pattern of variation was found in subgroup analysis except that the risk-adjusted
rate of in-hospital mortality was highest in the West among patients <65 years
(1.7% vs 1.2% [lowest] in the Midwest), male gender (3.2% vs 2.8% in the
Midwest), and rural location (3.8% vs 3% in the Midwest). In conclusion, HF
hospitalization outcomes tend to be worse in the Northeast compared with other
regions of the country. In addition, the in-hospital mortality rate was higher in
rural locations than in urban locations.
PMID- 28705377
TI - Load Adaptability in Patients With Pulmonary Arterial Hypertension.
AB - Right ventricular (RV) adaptation to pressure overload is a major prognostic
factor in patients with pulmonary arterial hypertension (PAH). The objectives
were first to define the relation between RV adaptation and load using allometric
modeling, then to compare the prognostic value of different indices of load
adaptability in PAH. Both a derivation (n = 85) and a validation cohort (n = 200)
were included. Load adaptability was assessed using 3 approaches: (1) surrogates
of ventriculo-arterial coupling (e.g., RV area change/end-systolic area), (2)
simple ratio of function and load (e.g., tricuspid annular plane systolic
excursion/right ventricular systolic pressure), and (3) indices assessing the
proportionality of adaptation using allometric pressure-function or size
modeling. Proportional hazard modeling was used to compare the hazard ratio for
the outcome of death or lung transplantation. The mean age of the derivation
cohort was 44 +/- 11 years, with 80% female and 74% in New York Heart Association
class III or IV. Mean pulmonary vascular resistance index (PVRI) was 24 +/- 11
with a wide distribution (1.6 to 57.5 WU/m2). Allometric relations were observed
between PVRI and RV fractional area change (R2 = 0.53, p < 0.001) and RV end
systolic area indexed to body surface area right ventricular end-systolic area
index (RVESAI) (R2 = 0.29, p < 0.001), allowing the derivation of simple
ratiometric load-specific indices of RV adaptation. In right heart parameters,
RVESAI was the strongest predictor of outcomes (hazard ratio per SD = 1.93, 95%
confidence interval 1.37 to 2.75, p < 0.001). Although RVESAI/PVRI0.35 provided
small incremental discrimination on multivariate modeling, none of the load
adaptability indices provided stronger discrimination of outcome than simple RV
adaptation metrics in either the derivation or the validation cohort. In
conclusion, allometric modeling enables quantification of the proportionality of
RV load adaptation but offers small incremental prognostic value to RV end
systolic dimension in PAH.
PMID- 28705378
TI - Reliability of Cardiovascular Risk Calculators to Estimate Accurately the Risk of
Cardiovascular Disease in Patients With Sarcoidosis.
AB - Chronic inflammation is an independent risk factor for cardiovascular disease
(CVD), but most risk calculators, including the Framingham risk score (FRS) and
the American College of Cardiology (ACC)/American Heart Association (AHA) risk
score do not account for it. These calculators underestimate cardiovascular risk
in patients with rheumatoid arthritis and systemic lupus erythematosus. To date,
how these scores perform in the estimation of CVD risk in patients with
sarcoidosis has not been assessed. In this study, the FRS and the ACC/AHA risk
score were calculated for a previously identified cohort of patients with
incident cases of sarcoidosis in Olmsted County, Minnesota, United States, from
1989 to 2013 as well as their gender- and age-matched comparators. The
standardized incidence ratio (SIR) was estimated as the ratio of the predicted
and observed numbers of CVD events. All CVD events were identified by diagnosis
codes and were verified by individual medical record reviews. The predicted
number of CVD events among 188 cases by FRS was 11.8 and the observed number of
CVD events was 34, which corresponded to an SIR of 2.88 (95% confidence interval
2.06 to 4.04). FRS underestimated the risk of CVD events in patients with
sarcoidosis by gender, age and severity of sarcoidosis. The predicted number of
CVD events among cases by ACC/AHA risk score was 4.6 and the observed number of
CVD events was 19, corresponding to an SIR of 4.11 (95% confidence interval 2.62
to 6.44). In conclusion, the FRS and the ACC/AHA risk score underestimate the
risk of CVD in patients with sarcoidosis.
PMID- 28705379
TI - Prognostic Usefulness of Cardiopulmonary Exercise Testing for Managing Patients
With Severe Aortic Stenosis.
AB - The approach to managing asymptomatic or questionably symptomatic patients for
aortic stenosis is difficult. We aimed to determine whether cardiopulmonary
exercise testing (CPET) is prognostically useful in such patients. Patients
judged asymptomatic or questionably symptomatic for aortic stenosis with aortic
valve area index <0.6 cm2/m2 and left ventricular ejection fraction >=0.50 were
managed conservatively provided they had either (group 1) normal peak oxygen
consumption and peak oxygen pulse (>83% and >95% of the predicted values,
respectively) or (group 2) subnormal peak oxygen consumption or peak oxygen pulse
but with CPET data pointing to pathologies other than hemodynamic compromise from
aortic stenosis. Increase in systolic blood pressure <20 mm Hg, ST depression >=2
mm, or symptoms during the exercise test were allowed. Unexpected events included
cardiac death or hospitalization with heart failure in patients who had not been
recommended valve replacement. The median age of the study population (n = 101)
was 75 years (interquartile range 65 to 79 years), and 67% were judged
questionably symptomatic. During a follow-up at 24 +/- 6 months, the rate of
unexpected cardiac death and unexpected hospitalization with heart failure was 0%
and 6.0%, respectively. All-cause mortality was 4.0% compared with 8.0% in the
age- and gender-matched population. For group 1, 26 of 70 (37.1%) succumbed to
cardiac death, or were hospitalized because of heart failure, or underwent valve
replacement, and for group 2 this was 12 of 31 (38.7%). In conclusion, if CPET
does not indicate a significant hemodynamic compromise because of aortic
stenosis, an initially conservative strategy results in a good prognosis and an
acceptable event rate.
PMID- 28705380
TI - Air Pollution and Hospitalization for Acute Myocardial Infarction in China.
AB - There is growing interest in the association between ambient air pollution and
acute myocardial infarction (AMI). The objective of this study was to explore the
association in 14 Chinese cities using a time-stratified case-crossover design.
We identified 80,787 hospital admissions for AMI between January 1, 2014 and
December 31, 2015 from electronic hospitalization summary reports. Conditional
logistic regression was used to estimate the percent changes with 95% confidence
intervals (CIs) in AMI admissions in relation to an interquartile range increase
in ambient air pollutant concentrations. All analyzed air pollutants, with the
exception of ozone, were positively associated with daily AMI admissions on lag2
and lag3 days. An interquartile range increase in particulate matter <10 um in
aerodynamic diameter, sulfur dioxide, nitrogen dioxide, and carbon monoxide
concentrations on lag2 day was significantly associated with a 0.8% (95% CI 0.1%,
1.6%), 2.0% (95% CI 1.2%, 2.9%), 2.2% (95% CI 1.4%, 3.1%), and 1.1% (95% CI 0.4%,
1.8%) increase in AMI admissions, respectively. We also observed a significant
association in relation to ozone on lag4 day (percent change: 1.3%; 95% CI 0.2%,
2.4%). Subgroup analyses indicated no effect modification of risk by age (>=65
years and <65 years) or gender. In conclusion, this is the first multicity study
in China, or even in other developing countries, to report the short-term effects
of air pollution on AMI morbidity. Our findings contribute to the limited
scientific data on the effects of ambient air pollution on AMI in developing
countries.
PMID- 28705381
TI - Usefulness of Atrial Premature Complexes on Routine Electrocardiogram to
Determine the Risk of Atrial Fibrillation (from the REGARDS Study).
AB - Atrial premature complexes (APCs) serve as acute triggers for atrial fibrillation
(AF), but it is currently unknown whether the association between APCs and AF
varies by race or sex. We examined the association between APCs and AF in 13,840
(mean age = 63 +/- 8.4 years; 56% women; 37% black) participants from the REasons
for Geographic And Racial Differences in Stroke study. APCs were detected on
baseline electrocardiograms (2003 to 2007). Incident AF was identified by study
scheduled electrocardiograms and self-reported history at a follow-up
examination. Logistic regression was used to compute odds ratios (OR) and 95%
confidence intervals for the association between APCs and incident AF. A total of
950 participants (6.9%) had APCs at the baseline visit. After a median follow-up
of 9.4 years, 1015 incident AF cases (7.3%) were detected. APCs were associated
with an increased risk of AF (odds ratios = 1.92, 95% confidence intervals =
1.57, 2.35). The relation between APCs and AF did not vary by race (interaction p
value = 0.56) or sex (interaction p value = 0.66). In conclusion, APCs detected
on a routine electrocardiogram are associated with an increased risk of AF
development, and this association does not vary by race or sex. The findings of
this analysis suggest that the risk of AF associated with atrial ectopy does not
account for the differential risk of AF that is observed in whites compared with
blacks, and in men compared with women.
PMID- 28705382
TI - Impact of Cardiorespiratory Fitness and Risk of Systemic Hypertension in Nonobese
Versus Obese Men Who Are Metabolically Healthy or Unhealthy.
AB - Few data are available regarding the influence of body phenotype on systemic
hypertension (SH) and whether cardiorespiratory fitness (CRF) attenuates this
relation. We tested the hypothesis that obesity phenotypes and CRF would predict
incident hypertension, evaluating 3,800 Korean men who participated in 2 health
examinations in1998 to 2009. All participants were normotensive at baseline and
were divided into 4 groups based on body mass index using the Asia-Pacific
descriptors for obesity and metabolic health status and the National Cholesterol
Education Program's adult treatment panel III (ATP-III) criteria. A metabolically
healthy obese (MHO) phenotype was defined as a body mass index of >=25 kg/m2 with
<2 metabolic abnormalities. CRF was directly measured by peak oxygen uptake, and
the participants were divided into unfit and fit categories based on age-specific
peak oxygen uptake percentiles. Compared with the metabolically healthy nonobese
phenotype, MHO and metabolically unhealthy nonobese (MUNO) phenotypes were at
increased risk of SH (relative risk [RR] = 1.47; 95% confidence interval [CI],
1.07 to 2.02 and 1.62, 1.21 to 2.16) after adjusting for potential confounders.
Joint analysis showed that MHO or MUNO unfit men had 1.91 and 2.27 greater risk
of incident SH, respectively. However, MHO fit men had no significant RR of
incident SH (RR 1.37; 95% CI, 0.93 to 2.03), whereas MUNO fit men remained at
increased risk (RR 1.48; 95% CI, 1.04 to 2.11) compared with their metabolically
healthy nonobese fit counterparts. In conclusion, MHO and MUNO men were at
increased risk of SH, but these risks were attenuated by fitness.
PMID- 28705384
TI - The shedding protease ADAM17: Physiology and pathophysiology.
AB - The disintegrin metalloprotease ADAM17 has been a matter of intense studies
aiming to unravel structure, function and regulation of protease expression,
maturation and activity. In this review, we summarize data on the physiological
role of ADAM17 in health and disease. Here we provide an overview of ADAM17
substrates, mouse models of ADAM17-deficiencies and discuss recent findings of
ADAM17 function in the immune system and central nervous system as well as in
cancer. Whereas ADAM17 function in EGF-R-, in Interleukin-6 (IL-6)- and in
TNFalpha-biology has been shown to play a decisive role in regulation of the
immune system as well as cancer development, the role of ADAM17 in the central
nervous system and neurodegeneration still remains elusive. We show ADAM17
expression in human dopaminergic neurons derived from induced pluripotent stem
cells and we discuss how this state-of-the-art technology can be further
exploited to study the function of this important protease in the brain and other
tissues. This article is part of a Special Issue entitled: Proteolysis as a
Regulatory Event in Pathophysiology edited by Stefan Rose-John.
PMID- 28705385
TI - Pneumothorax Due to Radiofrequency Ablation for Post-herpetic Neuralgia.
PMID- 28705386
TI - A Rare Case of Chylothorax. Gorham-Stout Syndrome.
PMID- 28705387
TI - Alveolar Emptying in Mechanical Ventilation.
PMID- 28705383
TI - Ischemic or Nonischemic Functional Mitral Regurgitation and Outcomes in Patients
With Acute Decompensated Heart Failure With Preserved or Reduced Ejection
Fraction.
AB - The aim of this study was to evaluate the association of functional mitral
regurgitation (FMR), preserved or reduced ejection fraction (EF), and ischemic or
nonischemic origin with outcomes in patients discharged alive after
hospitalization for acute decompensated heart failure (HF). Of the 4,842 patients
enrolled in the Acute Decompensated Heart Failure Syndromes (ATTEND) registry,
3,357 patients were evaluated to assess the association of FMR, preserved or
reduced EF, and ischemic or nonischemic origin with the primary end point (all
cause death and readmission for HF after discharge). At the time of discharge,
FMR was assessed semiquantitatively (classified as none, mild, or moderate to
severe) by color Doppler analysis of the regurgitant jet area. According to
multivariable analysis, in the ischemic group, either mild or moderate to severe
FMR in patients with a preserved EF had a significantly higher risk of the
primary end point than patients without FMR (hazard ratio [HR] 1.60; 95%
confidence interval [CI] 1.12 to 2.29; p = 0.010 and HR 1.98; 95% CI 1.30 to
3.01; p = 0.001, respectively). In patients with reduced EF with an ischemic
origin, only moderate to severe FMR was associated with a significantly higher
risk of the primary end point (HR 1.67; 95% CI 1.11 to 2.50; p = 0.014). In the
nonischemic group, there was no significant association between FMR and the
primary end point in patients with either a preserved or reduced EF. In
conclusion, among patients with acute decompensated HF with a preserved or
reduced EF, the association of FMR with adverse outcomes may differ between
patients who had an ischemic or nonischemic origin of HF.
PMID- 28705388
TI - The Good, the Bad and the Ugly of the Next-Generation Xpert Mtb/Rif(r) Ultra Test
for Tuberculosis Diagnosis.
PMID- 28705389
TI - Tracheobronchial Tuberculosis.
PMID- 28705390
TI - Alpha-1-Antitrypsin Deficiency Associated With Null Alleles.
PMID- 28705391
TI - Current Indications For Surgical Treatment of Lung Metastases.
PMID- 28705392
TI - Phylogenetic and phenotypic characterisation of Sirococcus castaneae comb. nov.
(synonym Diplodina castaneae), a fungal endophyte of European chestnut.
AB - In this paper we resolve the taxonomic status of the fungus Diplodina castaneae
(Ascomycetes, Diaporthales, Gnomoniaceae) which occurs on the European chestnut
(Castanea sativa) as endophyte and as the causal agent of Javart disease.
Specimens from Switzerland, Spain, and Azerbaijan were sequenced at five nuclear
loci (beta-tubulin, EF-1alpha, ITS, LSU, and RPB2). Phylogenies were inferred to
place D. castaneae in the Gnomoniaceae family. Moreover, growth rates and
morphological characteristics on different agar media were assessed and compared
to those of Gnomoniopsis castaneae, which can easily be confused with D.
castaneae. Based on morphological and phylogenetic characteristics, we propose to
reallocate D. castaneae to the genus Sirococcus, as S. castaneae comb. nov.
PMID- 28705393
TI - The Gondwanan connection - Southern temperate Amanita lineages and the
description of the first sequestrate species from the Americas.
AB - Amanita is a diverse and cosmopolitan genus of ectomycorrhizal fungi. We describe
Amanita nouhrae sp. nov., a new hypogeous ('truffle-like') species associated
with Nothofagus antarctica in northern Patagonia. This constitutes the first
report of a sequestrate Amanita from the Americas. Thick-walled basidiospores
ornamented on the interior spore wall ('crassospores') were observed consistently
in A. nouhrae and its sister epigeous taxon Amanita morenoi, a rarely collected
but apparently common species from northern Patagonia that has sometimes been
misidentified as the Australian taxon Amanita umbrinella. Nuclear 18S and 28S
ribosomal DNA and mitochondrial 16S and 26S DNA placed these two species in a
southern temperate clade within subgenus Amanita, together with other South
American and Australian species. Based on a dated genus-level phylogeny, we
estimate that the southern temperate clade may have originated near the
Eocene/Oligocene boundary (ca. 35 Ma +/- 10 Ma). This date suggests a broadly
distributed ancestor in the Southern Hemisphere, which probably diversified as a
result of continental drift, as well as the initiation of the Antarctic
glaciation. By comparison, we show that this clade follows an exceptional
biogeographic pattern within a genus otherwise seemingly dominated by Northern
Hemisphere dispersal.
PMID- 28705394
TI - Melanization and ageing are not drawbacks for successful agro-transformation of
dark septate endophytes.
AB - Dark septate endophytes (DSEs) are melanin-enriched ascomycetous fungi that are
abundant in stressed environments. However, little is known about their
physiology and metabolism, and DSE genes have not been functionally characterized
yet. Therefore developing molecular genetic tools to investigate the biological
function of genes of interest in DSEs is of major significance. We investigated
Agrobacterium tumefaciens-mediated transformation (ATMT) efficiency in eight DSE
strains belonging to Cadophora sp., Cadophora malorum, Leptodontidium sp.,
Phialophora mustea, and Cladosporium cladosporioides. ATMT efficiency was DSE
dependent and ranged from 0.6 to 125 %. We further focused on the effect of
mycelium ageing on ATMT efficiency. Leptodontidium sp. Me07, Leptodontidium sp.
Pr30, and C. cladosporioides CBS 101367 were significantly more transformed using
15-d-old mycelium (44.5, 6.9, and 1.1 %, respectively) as compared to 2-d-old
mycelium (121, 28.7, and 25.1, respectively), whereas P. mustea Pr29 was more
transformed using young mycelium (21.5 % compared to 5.3 % for the old mycelium).
Finally, we focused on the effect of melanin content on ATMT efficiency. Melanin
content in mycelium ranged from 0.9 to 3.2 mg g-1 DW. Tricyclazole negatively
modulated melanin content, while copper positively modulated it. However there
was no correlation between hyphal melanin content and ATMT efficiency.
PMID- 28705395
TI - Targeted disruption of the polyketide synthase gene pks15 affects virulence
against insects and phagocytic survival in the fungus Beauveria bassiana.
AB - The reducing clade III polyketide synthase genes, including pks15, are highly
conserved among entomopathogenic fungi. To examine the function of pks15, we used
targeted disruption to investigate the impact of Beauveria bassiana pks15 on
insect pathogenesis. Southern analysis verified that the Deltapks15 mutant was
disrupted by a single integration of the transformation cassette at the pks15
locus. The Deltapks15 mutant had a slight reduction in radial growth, and it
produced fewer spores. Our insect bioassays indicated the Deltapks15 mutant to be
significantly reduced in virulence against beet armyworms compared to wild type
(WT), which could be partially accounted for by its markedly decreased ability to
survive phagocytosis. Total haemocyte count decreased sharply by 50-fold from
days 1-3 post-inoculation in insects infected with WT, compared to a 5-fold
decrease in the Deltapks15 mutant. The mutant also produced fewer hemolymph
hyphal bodies than WT by 3-fold. In co-culture studies with amoebae that have
phagocytic ability similar to that of insect haemocytes, at 48 h the mortality
rate of amoebae engulfing Deltapks15 decreased by 72 %, and Deltapks15 CFU
decreased by 83 % compared to co-culture with WT. Thus, the Deltapks15 mutant had
a reduced ability to cope with phagocytosis and highly reduced virulence in an
insect host. These data elucidate a mechanism of insect pathogenesis associated
with polyketide biosynthesis.
PMID- 28705396
TI - Host extracts induce changes in the proteome of plant pathogen Fusarium
proliferatum.
AB - Fusarium proliferatum is a polyphagous pathogenic fungus able to infect many crop
plants worldwide. Differences in proteins accumulated were observed when maize-
and asparagus-derived F. proliferatum strains were exposed to host extracts
prepared from asparagus, maize, garlic, and pineapple tissues. Seventy-three
unique proteins were up-regulated in extract-supplemented cultures compared to
the controls. They were all identified using mass spectrometry and their putative
functions were assigned. A major part of identified proteins was involved in
sugar metabolism and basic metabolic processes. Increased accumulation of
proteins typically associated with stress response (heat shock proteins,
superoxide dismutases, and glutaredoxins) as well as others, putatively involved
in signal transduction, suggests that some metabolites present in plant extracts
may act as elicitors inducing similar reaction as the abiotic stress factors. As
a case study, thirteen genes encoding the proteins induced by the extracts were
identified in the genomes of diverse F. proliferatum strains using gene-specific
DNA markers. Extract-induced changes in the pathogen's metabolism are putatively
a result of differential gene expression regulation. Our findings suggest that
host plant metabolites present in the extracts can cause biotic stress resulting
in elevated accumulation of diverse set of proteins, including those associated
with pathogen's stress response.
PMID- 28705397
TI - Taxonomy and phylogeny of the Auriculariales (Agaricomycetes, Basidiomycota) with
stereoid basidiocarps.
AB - In the present study, we investigate taxonomy of the Auriculariales with effused
or cupulate, persistent basidiocarps; generic and species concepts are revised
based on morphological and DNA evidences. The genus Eichleriella is reinstated to
embrace ten closely related species with ellipsoid-ovoid basidia, and the genus
type, Eichleriella incarnata, is placed to the synonyms of Eichleriella
leucophaea. Eichleriella bactriana, Eichleriella desertorum and Eichleriella
sicca are described as new to science. In addition, four species earlier treated
as members of Exidiopsis or Heterochaete are combined to the genus. The genus
name Heteroradulum (type Radulum kmetii) is introduced for seven species with
large, obconical, stipitate basidia. Of them, Heteroradulum adnatum and
Heteroradulum semis are described as new. Two new genera, Amphistereum (with two
species, type Eichleriella schrenkii) and Sclerotrema (monotypic, type Exidiopsis
griseobrunnea), are proposed; Hirneolina (monotypic, type H. hirneoloides) and
Tremellochaete (with two species, type Exidia japonica) are restored as good
genera. The type species of Heterochaete, H. andina, is congeneric with
Exidiopsis (type E. effusa).
PMID- 28705398
TI - Very-long-chain aldehydes induce appressorium formation in ascospores of the
wheat powdery mildew fungus Blumeria graminis.
AB - Asexually produced conidia of the wheat powdery mildew fungus Blumeria graminis
f. sp. tritici (Bgt) are known to perceive cuticular very-long-chain aldehydes as
signal substances strongly stimulating germination and differentiation of
infection structures in a concentration- and chain-length-dependent manner.
Conidial germination and appressorium formation are widely prevented by the
presence of free water on the host surface. However, sexually produced ascospores
can differentiate immersed in water. Applying a Formvar(r)-based in vitro-system
showed that ascospore appressorium formation was strongly induced by the presence
of wheat leaf cuticular wax. Similar to conidia, ascospore appressorium formation
is triggered by the presence of very-long-chain aldehydes in a chain-length
dependent manner with n-octacosanal as the most inducing aldehyde. Surface
hydrophobicity positively affected ascospore germination but not appressorium
formation. Ascospores required significantly more time to complete the
differentiation of appressoria and exhibited a more distinct dependence on the
availability of free water than their conidial counterparts. Unlike conidia,
ascospores showed a more variable germination and differentiation pattern even
with a single germ tube differentiating an appressorium. Despite these
differences our results demonstrate that a host surface recognition principle
based on cuticular very-long-chain aldehydes is a common feature of B. graminis
f. sp. tritici ascospores and conidia.
PMID- 28705399
TI - Monoblepharidomycetes diversity includes new parasitic and saprotrophic species
with highly intronized rDNA.
AB - The Monoblepharidomycetes is the sister class to the Chytridiomycetes in the
phylum Chytridiomycota. The six known genera have thalli that are either
monocentric and without rhizoids or produce hyphae with an independent
evolutionary origin from the hyphae of higher fungi. On the basis of
morphological characters and phylogenetic evidence from the small and large
subunits of nuclear ribosomal RNA, we established two new genera, Sanchytrium and
Telasphaerula, each with a single species. We re-analyzed intergeneric
relationships within the monoblephs, and established two new families. The new
genera significantly expand the known morphological and ecological diversity of
the Monoblepharidomycetes by adding a monocentric, epibiotic, algal parasitic
species and a rhizomycelial, saprotrophic species. Based on the presence of
environmental sequences related to Sanchytrium strains, the Monoblepharidomycetes
contain previously unsuspected diversity. The ribosomal DNA of the new genera
contains an unusually high density of group I introns. We found 20 intron
insertion positions including six that are new for rRNA genes (S1053, L803, L829,
L961, L1844, and L2281).
PMID- 28705400
TI - [Have general practitioners integrated direct oral anticoagulants in their
practices?]
PMID- 28705401
TI - [Are general practitioners in Paris and surrounding areas reticent about direct
oral anticoagulants?]
AB - OBJECTIVE: Determine how familiar general practitioners (GPs) working in Paris
and surrounding areas are with prescriptions for direct oral anticoagulants
(DOACs). MATERIAL AND METHOD: A questionnaire sent to 189 GP working in Paris and
surrounding areas yielded 100 responses. Data collected included a brief summary
of sociodemographic items, comparative knowledge about DOACs and vitamin K
antagonists (VKAs), and responses to two clinical situations for DOAC
prescriptions (renewal of a first prescription). RESULTS: The majority (65%) of
the responding GPs were over 50. The GPs were knowledgeable about data in the
literature concerning the following items: patient quality of life (72%
considered it improved); adherence (55% suggested it was improved); rules for
DOAC prescription (88% knew the set doses; 81% knew biological monitoring does
not exist; 38% were aware of potential interactions). They were not knowledgeable
about the following points: main sites for bleeding risks are the gut and the
brain; 44% thought risk was lowered for gastrointestinal bleeding and concerning
brain hemorrhages 26% thought there was a lesser risk while 40% had no opinion;
cost (20% thought it was lower). For prescription modalities, 90% of the GPs
renewed the DOAC previously prescribed for non-valvular atrial fibrillation while
76% preferred a LMWH-VKA scheme for the first prescription for deep vein
thrombosis. CONCLUSION: Without being reticent about DOACs, the GPs questioned in
this study recognized the usefulness of these medications for their patients'
quality of life but were hesitant to use DOACs as the first intention
anticoagulant, undeniably due to lack of experience and knowledge about the lower
risk of bleeding. Initial training and continuing education should be
strengthened on this point with dedicated workshops.
PMID- 28705402
TI - [Development of an objective structured clinical examination (OSCE) for
evaluating clinical competence in vascular medicine].
AB - OBJECTIVES: Vascular medicine is now a clinical specialty in France. During their
studies, students will acquire clinical reasoning in addition to technical
skills. An Objective Structured Clinical Examination (OSCE) is considered as the
gold standard for evaluating clinical competence. Our main objective was to
evaluate the feasibility and acceptability of OSCE for the evaluation of
students, secondarily their performance. METHODS: Three representative clinical
cases of the specialty were developed. The OSCE consisted of a sequence of
clinical situations presented in three stations of 7minutes each. The role of the
simulated patient was played by medical students. At the end of the OSCE,
observers and students completed the evaluation form. We compared the
performances between junior and senior vascular medicine students. Written
questionnaires were used to measure OSCE satisfaction. RESULTS: We were able to
develop and organize this examination without difficulties. Fifteen students were
evaluated. All participants agreed that the clinical situations were
representative of vascular medicine practice, the cases were realistic and
standardized patients were convincing. The performance of senior students was
statistically higher than junior students in one case. DISCUSSION: Our study
demonstrates the feasibility and acceptability of the OSCE in students in
vascular medicine. The small number of stations and candidates requires further
studies on a larger scale to evaluate their performance.
PMID- 28705403
TI - Symptomatic lower-limb giant-cell arteritis: Characteristics, management and long
term outcome.
AB - OBJECTIVE: To describe characteristics and long-term outcomes of the rare
symptomatic lower-limb giant-cell arteritis (LL-GCA). METHODS: Retrospective
analysis of 8 patients (6 women; mean+/-SD age, 63.6+/-10.9 years; follow-up,
137.3+/-57.3 months). RESULTS: Four patients satisfied>=3 American College of
Rheumatology (ACR) GCA-classification criteria; 4 had<3 criteria and histological
LL-GCA proof or associated typical upper-limb involvement. Patients had 2.1+/-1.1
vascular risk factors. Bilateral and rapidly progressive arterial claudication
was the first LL sign; 2 had rest ischemia. Imaging-visualized most-to-least
frequent inflammatory lesion localizations were: superficial femoral, popliteal,
tibiofibular trunk, posterior tibial arteries. All received corticosteroids for
132+/-76.2 months; 2 required immunosuppressive agent adjunction. Only 3 required
1-6 revascularizations: twice during the first month post-diagnosis and twice
later. Thromboendarterectomy and endovascular procedures did not work while
bypasses were successful. LL-claudication regressed for 7 (10.5+/-12.1 months)
and disappeared for 5 (16.8+/-9.8 months). Three patients stopped corticosteroids
(26-90 months), 1 restarted 45 months later. Every patient relapsed once (23.9+/
26.7 months, mean corticosteroid dose: 0.28+/-0.30mg/kg/day). LL-GCA caused only
1 of the 4 deaths. CONCLUSION: Symptomatic LL-GCA attributable long-term
mortality seems to be low despite frequent relapses and corticosteroid
dependence.
PMID- 28705404
TI - Midterm results of internal iliac artery aneurysm embolization.
AB - OBJECTIVE: We describe the immediate and midterm results of endovascular
treatment of isolated internal iliac artery aneurysms (IIAA). METHODS: This was a
retrospective single center study. From 2005 to 2014, data from 20 consecutive
patients who had an embolisation for an isolated atherosclerotic internal iliac
artery aneurysm underwent an endovascular treatment. We retrospectively evaluated
the technical aspects and outcomes. RESULTS: The mean aneurysm diameter was 42mm
(range 30-97mm). No perioperative deaths or treatment failures occurred. No
endoleaks or secondary aneurysm ruptures were observed during the follow-up.
Three patients experienced disabling buttock claudication, which was
spontaneously remissive in two cases. No relationship was found between buttock
claudication and the patency of the contralateral internal iliac artery and the
deep femoral artery. Six patients (30%) died during follow-up. Among these, three
patients died due to cardiovascular events. The mean follow-up interval was 24
months (range 6-96 months). CONCLUSION: The endovascular treatment of isolated
internal iliac artery aneurysm is safe in the short-term and could prevent
secondary aneurysm rupture at midterm.
PMID- 28705405
TI - [Sleep apnea syndrome and abdominal aortic aneurysm: Study of the prevalence of
sleep apnea syndrome in patients with aneurysm and research of association.
Clinical study on 52 patients].
AB - OBJECTIVES: Prevalence of abdominal aortic aneurysms (AAA) in Europe is between
4.1 % and 8.9 %. The risk of rupture of AAA is related to the evolution of its
diameter. The role of sleep apnea (SA) remains still discussed. The objective of
this study was to study the prevalence of SA in patients presenting with AAA in
comparison with the general population as well as the relation between the AAA
diameter and the severity of SA. MATERIALS AND METHODS: Between June 2012 and
December 2014, we included all patients referred for surgical treatment of an
AAA. All the patients had a preoperative polysomnography and angio-scanner. An
apnea/hypopnea index (AHI)>10/h was chosen for the diagnosis of SA. SA prevalence
was compared with the prevalence in general population. The patients were also
divided into two groups according to the severity of SA: group 1 (no SA and light
SAS); group 2 (moderate and severe SA). RESULTS: Fifty-two patients were
included. Fifty-six percent of the patients presented SA - prevalence was
significantly higher than in the general population (56 vs. 8 %, P<0.001). The
distribution of the two groups was: group 1, n=27 patients, group 2, n=25
patients. AAA diameter and BMI were higher in group 2 than in group 1,
respectively 61mm vs. 55mm, P=0.03 and 28 vs. 23, P=0.02. CONCLUSION: Prevalence
of SA in patients with an AAA seems to be significantly higher than in general
population. The growth of the aneurysm seems to be linked to the severity of SA.
PMID- 28705406
TI - [Quality standards for duplex ultrasonographic assessment (duplex us) of
abdominal aortic stent grafts].
AB - : The quality standards of the French Society of Vascular Medicine for the
ultrasound assessment of lower limb arteries in vascular medicine practice are
based on the principle that these examinations have to meet two requirements:
technical know-how (knowledge of devices and methodologies); medical know-how
(level of examination matching the indication and purpose of the examination,
interpretation and critical analysis of results). OBJECTIVES OF THE QUALITY
STANDARDS: To describe an optimal level of examination adjusted to the indication
or clinical hypothesis; to establish harmonious practices, methodologies,
terminologies, results description and report; to provide good practice reference
points and to promote a high quality process. THEMES OF THE QUALITY STANDARDS:
The three levels of examination, indications and objectives for each level; the
reference standard examination (level 2) and its variants according to
indications; the minimal content of the exam report, the medical conclusion
letter to the corresponding physician (synthesis, conclusion and management
suggestions); commented glossary (anatomy, hemodynamics, signs and symptoms);
technical basis; device settings. Here, we discuss duplex ultrasound for the
supervision of the aortic stent grafts.
PMID- 28705407
TI - [False aneurysm of the carotid artery revealing Behcet disease].
AB - Vascular involvement in Behcet's disease often present as venous thrombosis.
Arterial damage is rare. We report a case of Behcet's disease occurring in a 40
year-old woman revealed by a false aneurysm of the left common carotid artery.
The intervention consisted in a prosthetic graft after endovascular control.
After a 2-year follow-up period, the patient did not develop any postoperative
complication.
PMID- 28705409
TI - Clinical benefit and risk of death with endocrine therapy in ovarian cancer: A
comprehensive review and meta-analysis.
AB - BACKGROUND: Steroid hormones promote epithelial ovarian cancer (EOC) growth and
their receptor expression is associated with disease outcome. Hormone therapy is
frequently used in pretreated EOC, but the magnitude of activity overall and by
specific agents or tumor characteristics is unknown. METHODS: Clinical Benefit
Rates (CBR) and deaths from clinical trials of endocrine agents were meta
analyzed. Summary estimates of CBR (SCBR) and Odd Ratio for death (SOR) were
calculated according with type of drug, ER and PgR status, platinum resistance,
line of therapy, tumor grade and tamoxifen dose. RESULTS: Fifty-three trials in
2490 patients were analyzed. Overall, SCBR was 41% (95%CI, 0.34-0.48) for any
endocrine treatment, 43% (95%CI, 0.30-0.56) for tamoxifen, 39% (95%CI, 0.29-0.50)
for aromatase inhibitors and 37% (95%CI, 0.26-0.48) for progestins. The SCBR for
ER+ and/or PgR+ tumors was 46% (95%CI, 0.34-0.57) versus 37% (95%CI, 0.27-0.48)
in tumors with unknown receptors and 55% in platinum sensitive (95%CI, 0.28-0.80)
versus 40% (95%CI, 0.29-0.51) in platinum resistant tumors The SOR for death
calculated from 6 out of 9 randomized clinical trials (RCTs) showed a reduced
mortality with endocrine therapy (SOR=0.69, 95%CI, 0.50-0.97), with a possible
tendency for a greater effect in first line and low grade tumors. The overall
quality of the RCTs was low. CONCLUSIONS: The activity of endocrine therapy in
advanced EOC is worth considering and seems to support large properly designed
randomized trials in the first treatment of hormone sensitive EOC.
PMID- 28705408
TI - Superior in vitro and in vivo activity of trastuzumab-emtansine (T-DM1) in
comparison to trastuzumab, pertuzumab and their combination in epithelial ovarian
carcinoma with high HER2/neu expression.
AB - BACKGROUND: Epithelial ovarian cancer (EOC) remains the most lethal gynecologic
malignancy. The objective of this study was to compare the anti-tumor activity of
HER2/neu-targeting monoclonal antibodies, trastuzumab (T), pertuzumab (P),
combination of trastuzumab and pertuzumab (T+P) and trastuzumab-emtansine (T-DM1)
in EOC with high HER2/neu expression. METHODS: Primary EOC cell lines were
established and cell blocks were analyzed for HER2/neu expression. Cytostatic,
apoptotic and antibody-dependent cell-mediated cytotoxicity (ADCC) activities of
T, P, T+P and T-DM1 were evaluated in vitro. The in vivo antitumor activity was
tested in xenograft models with 3+ HER2/neu expression. RESULTS: High (3+)
HER2/neu expression was detected in 40% of the primary EOC cell lines. T, P, T+P,
and T-DM1 were similarly effective in inducing strong ADCC against primary EOC
cell lines expressing 3+ HER2/neu. The combination of T and P was more cytostatic
when compared with that of T or P used alone (p<0.0001 and p<0.0001,
respectively). T-DM1 induced significantly more apoptosis when compared with T+P
(p<0.0001). Finally, T-DM1 was significantly more effective in tumor growth
inhibition in vivo in EOC xenografts overexpressing HER2/neu when compared to T
alone, P alone and T+P (p=0.04). CONCLUSION: In vitro and in vivo experiments
with 3+ HER2/neu expressing EOC revealed limited anti-tumor activity of T or P. T
DM1 showed superior anti-tumor activity to T and P as single agents and as a
combination. Our preclinical data support the design of clinical studies with T
DM1 for the treatment of chemotherapy-resistant EOC overexpressing HER2/neu.
PMID- 28705410
TI - A level-set approach to joint image segmentation and registration with
application to CT lung imaging.
AB - Automated analysis of structural imaging such as lung Computed Tomography (CT)
plays an increasingly important role in medical imaging applications. Despite
significant progress in the development of image registration and segmentation
methods, lung registration and segmentation remain a challenging task. In this
paper, we present a novel image registration and segmentation approach, for which
we develop a new mathematical formulation to jointly segment and register three
dimensional lung CT volumes. The new algorithm is based on a level-set
formulation, which merges a classic Chan-Vese segmentation with the active dense
displacement field estimation. Combining registration with segmentation has two
key advantages: it allows to eliminate the problem of initializing surface based
segmentation methods, and to incorporate prior knowledge into the registration in
a mathematically justified manner, while remaining computationally attractive. We
evaluate our framework on a publicly available lung CT data set to demonstrate
the properties of the new formulation. The presented results show the improved
accuracy for our joint segmentation and registration algorithm when compared to
registration and segmentation performed separately.
PMID- 28705411
TI - Erratum to "Recurrence of gallstone disease following non-surgical treatment of
acute cholecystitis in the elderly population" [MedClin(Barc) 148(12) (2017) 569
572].
PMID- 28705412
TI - Relationship between structure of macrobenthic assemblages and environmental
variables in shallow sublittoral soft bottoms.
AB - We establish baseline knowledge of abundance, diversity and multivariate
structure of macrobenthos from shallow sublitoral soft bottoms in the North
Portuguese coast and elucidate main environmental factors that shape their
spatial patterns. In this area distribution of soft bottoms is patchy, surrounded
by boulders and rocky substrates. This particular landscape and the lack of
significant anthropogenic disturbances are values for the conservation of this
habitat. Sediment and physicochemical properties of the water column were studied
to provide models for each studied macrobenthic variable. Our models highlighted
that most of variation (59%-72%) in macrobenthic spatial patterns was explained
by the studied environmental variables. Sedimentary variables were more relevant
that those of the water column. Therefore, disturbances affecting sedimentary
environment could cause dramatic changes in macrobenthic assemblages because of
the limited availability of soft bottoms in the area. In this way, results are
useful to adopt right management and conservation strategies.
PMID- 28705413
TI - Seawater-temperature and UV-radiation interaction modifies oxygen consumption,
digestive process and growth of an intertidal fish.
AB - UV-radiation (UVR) and temperatures have increased substantially over recent
decades in many regions of the world. Both stressors independently have shown to
affect the metabolism and growth in fish. However, because increase of both
stressors are occurring concomitantly, to better understand their influences on
marine species, their combined effects were evaluated. We test the hypothesis
that UVR and temperature act synergistically affecting the metabolism, digestive
process and growth of an intertidal fish. Two UVR conditions (with and without
UVR) and two temperature levels (20 degrees C and 25 degrees C) were used. UVR
increase the oxygen consumption and this was associated to opaque feces
production. The absorption efficiency was higher without UVR at high temperatures
(25 degrees C) and with UVR at low temperatures (20 degrees C). Finally,
independent of UVR treatment, fish subjected to low temperature have higher
biomass than those of high temperature. The interaction between UVR and
temperature may influence on the physiology and growth of animals that inhabit in
extreme habitats as upper intertidal, it could pose significant functional for
aquatic animal survivorship.
PMID- 28705414
TI - [Acute respiratory distress syndrome secondary to a viper envenomation in
children].
AB - Viper envenomation is responsible for inflammatory disorders, hemorrhagic
complications, and local or extended necrosis. The occurrence of respiratory
complications such as Acute Respiratory Distress Syndrome (ARDS) is exceptional.
We report on the case of a 15-year-old with no particular history who had, 24h
after a viper bite, swelling of the right lower limb associated with blood
dyscrasia. Despite the administration of antivenom treatment, the progression was
marked by the onset of ARDS and the patient's death within 48h.
PMID- 28705415
TI - Invasive aspergillosis due to Neosartorya aureola in a recipient of kidney
transplantation.
PMID- 28705416
TI - Availability of antidotes in 70 hospitals in Catalonia, Spain.
AB - BACKGROUND AND OBJECTIVE: Antidotes may have a relevant role in acute
intoxication management and the time until its administration can influence
patient survival. PATIENTS AND METHOD: Study conducted by a questionnaire sent in
early 2015 to 70 hospitals in Catalonia providing emergency services. Qualitative
availability on each antidote was considered adequate when present in at least
80% of hospitals. The quantitative availability was considered adequate when at
least 80% of hospitals had the number of units of antidote recommended. RESULTS:
Lower complexity hospitals (level A) showed a percentage of adequate qualitative
and quantitative availability of 66.7 and 42.9% respectively. In higher
complexity hospitals (level B) qualitative and quantitative availability was
adequate in 64.5 and 38.7% of the antidotes respectively. Data showed no
differences between the different health regions as well as a positive
correlation (p<.05) between the number of emergencies attended and the percentage
of adequate qualitative availability. CONCLUSIONS: The availability of antidotes
in Catalonia hospitals is generally low and shows differences across health
regions and depending on level of complexity.
PMID- 28705417
TI - Multi-label classification methods for improving comorbidities identification.
AB - The medical diagnostic process may be supported by computational classification
techniques. In many cases, patients are affected by multiple illnesses, and more
than one classification label is required to improve medical decision-making. In
this paper, we consider a multi-perspective classification problem for medical
diagnostics, where cases are described by labels from separate sets. We attempt
to improve the identification of comorbidities using multi-label classification
techniques. Several investigated methods, which provide label dependencies, are
analysed and evaluated. The methods' performances are verified by experiments
conducted on four sets of medical data from subject patients. The results were
evaluated using several metrics and were statistically verified. We compare the
effects of the techniques that do and do not consider label correlations. We
demonstrate that multi-label classification methods from the first group
outperform the techniques from the second one.
PMID- 28705418
TI - Guest introduction.
PMID- 28705420
TI - Is it necessary to perform full pathologic review of all gastric remnants
following sleeve gastrectomy?
AB - BACKGROUND: This study attempts to determine if enough pathological abnormalities
in gastric remnants from sleeve gastrectomy exist to warrant full pathologic
evaluation in all remnants. METHODS: Data was collected on patients undergoing
sleeve gastrectomy between 08/01/2011 and 06/30/2014. Significant abnormalities
were classified as any pathology that might require follow-up or treatment beyond
standard follow-up. Age, comorbidities, gender, and Helicobacter pylori titers
were analyzed and compared with pathology specimens using 95% confidence
intervals and Phi contingency coefficients. RESULTS: Full pathologic evaluation
was available for 351/387 patients (91.2%). No examples of malignancy or
dysplasia were identified. Gastritis was the most common abnormality. There was a
statistically significant association between preoperative H. pylori and
significantly abnormal pathology (p = 0.003). Other comorbidities had no
association. CONCLUSIONS: These results suggest that full pathologic evaluation
of the gastric remnant following sleeve gastrectomy is unnecessary, particularly
when gross pathology is not noted at initial operation.
PMID- 28705421
TI - Bcl-2 inhibitors as anti-cancer therapeutics: The impact of and on calcium
signaling.
AB - Bcl-2-protein family members are essential regulators of apoptosis. Anti
apoptotic Bcl-2 proteins ensure cell survival via different mechanisms, including
via binding of pro-apoptotic Bcl-2-family members and the modulation of
intracellular Ca2+-transport systems. Many cancer cells upregulate these proteins
to overcome the consequences of ongoing oncogenic stress. Bcl-2 inhibition
leading to cell death, therefore emerged as a novel cancer therapy. Different Bcl
2 inhibitors have already been developed including the hydrophobic cleft
targeting BH3 mimetics, which antagonize Bcl-2's ability to scaffold and
neutralize pro-apoptotic Bcl-2-family members. As such, the BH3 mimetics have
progressed into clinical studies as precision medicines. Furthermore, new
inhibitors that target Bcl-2's BH4 domain have been developed as promising anti
cancer tools. Given Bcl-2's role in Ca2+ signaling, these drugs and tools can
impact Ca2+ signaling. In addition to this, some Bcl-2 inhibitors may have "off
target" effects that cause Ca2+-signaling dysregulation not only in cancer cells
but also in healthy cells, resulting in adverse effects. In this review, we aim
to provide an up-to-date overview of the involvement of intracellular Ca2+
signaling in the working mechanism and "off-target" effects of the different Bcl
2-antagonizing small molecules and peptides.
PMID- 28705422
TI - A critical review on sustainable biochar system through gasification: Energy and
environmental applications.
AB - This review lays great emphasis on production and characteristics of biochar
through gasification. Specifically, the physicochemical properties and yield of
biochar through the diverse gasification conditions associated with various types
of biomass were extensively evaluated. In addition, potential application
scenarios of biochar through gasification were explored and their environmental
implications were discussed. To qualitatively evaluate biochar sustainability
through the gasification process, all gasification products (i.e., syngas and
biochar) were evaluated via life cycle assessment (LCA). A concept of balancing
syngas and biochar production for an economically and environmentally feasible
gasification system was proposed and relevant challenges and solutions were
suggested in this review.
PMID- 28705423
TI - Carbon nanotube fiber mats for microbial fuel cell electrodes.
AB - Novel carbon nanotube based electrodes of microbial fuel cells (MFC) have been
developed. MFC is a promising technology for the wastewater treatment and the
production of electrical energy from redox reactions of natural substrates.
Performances of such bio-electrochemical systems depend critically on the
structure and properties of the electrodes. The presently developed materials are
made by weaving fibers solely comprised of carbon nanotubes. They exhibit a large
scale porosity controlled by the weaving process. This porosity allows an easy
colonization by electroactive bacteria. In addition, the fibers display a
nanostructuration that promotes excellent growth and adhesion of the bacteria at
the surface of the electrodes. This unique combination of large scale porosity
and nanostructuration allows the present electrodes to perform better than carbon
reference. When used as anode in a bioelectrochemical reactor in presence of
Geobacter sulfurreducens bacteria, the present electrodes show a maximal current
density of about 7.5mA/cm2.
PMID- 28705424
TI - Post implantation development reveals that biopsy procedure can segregate
"healthy" from "unhealthy" bovine embryos and prevent miscarriages.
AB - Embryo biopsy has been performed in bovine in vivo produced embryos for the last
twenty years, but little could be done with few embryonic cells in the past.
Recently, advances in single cell analysis enabled a wide range of applications
using embryo biopsy, from morphology to genetics analysis and different omics
techniques, which are promising for in vitro-fertilized (IVF) embryos. The aim of
this study was to address if biopsy procedure would affect post implantation
development of IVF blastocyts. Here we show that blastocyst stage do not affect
re-expansion of biopsied embryos (regular blastocyst: 73.7%; expanded blastocyst:
73.1%), but affects (p<0.05) implantation (regular blastocyst: 37.8%, expanded
blastocyst: 61.0%), so ideally biopsy should be performed in expanded
blastocysts. No detrimental effect of biopsy procedure was detected for post
implantation development (calving rates, Biopsy: 47.1%, Control: 41.9%), and
normal calves were born (Birth weight, Biopsy: 32.10+/-7.20kg; Control: 30.95+/
5.43kg). Surprisingly, we found interesting results suggesting embryo survival
can be increased with aggressive procedures (such as embryo biopsy), and this is
highly associated with early pregnancy loss (Biopsy: 0%, Control: 17.4%). This
finding also suggests morphological classification of day 7 blastocysts is far
from ideal, and supposedly, unhealthy embryos can implant but are bound to
miscarriage during the first trimester (non-biopsied embryos). Our results show
biopsy procedure is safe for bovine IVF embryos, and shed new light into the
importance of conceptus in early pregnancy loss in cattle.
PMID- 28705425
TI - Corrigendum to "Reproductive cycles of marine mammals" [Anim. Reprod. Sci. 124
(2011) 184-193].
PMID- 28705426
TI - Prioritization of health care and research given limited and too limited
resources.
PMID- 28705427
TI - Invasive disease by Streptococcus pyogenes: patients hospitalized for 6 years.
AB - INTRODUCTION AND OBJECTIVE: The last years an increase of severe cases of
invasive disease (ID) due to Streptococcus pyogenes or streptococcus b-hemolytic
group A (SGA) had been detected. The aim of this study was to analyze the
epidemiology and the clinical features of ID due to SGA in a tertiary Pediatric
Hospital. MATERIAL AND METHODS: Retrospective study in a Pediatric hospital, of
all in-patients with final diagnosis of ID due to SGA during 6 years (2009-2014).
To consider ID, SGA had to be isolated in sterile samples; in patients with
fascitis necroticans in skin samples or in any sample in patients with the
diagnostic of Streptococcal Toxic Shock Syndrome (STSS). The SSTS was defined as
hypotension and at least 2 of these criteria: renal failure, hepatic failure,
acute respiratory distress, tissue necrosis or desquamative erythematous rash.
Demographic data, type of infection, risk factors, clinical presentation,
analytical data at admission, treatment, need for admission to a pediatric
intensive care unit, microbiological data, hospital stay and evolution were
collected. RESULTS: Fifty-two (52) cases were included (12/10,000 of all
inpatients); 3 years-old was the medium age (p25-75: 1.4-6.9 years); 28 (53.8%)
were boys. Fourteen patients (26.9%) had risk factors. Fever was the major
symptom (51 patients, 98.1%). The skin lesions were the most frequent clinical
manifestations found (21; 40.4%). In 50 (96%) cases, SGA was isolated in at least
one sterile sample. Skin and soft tissue infections were diagnosed in 14 patients
(26.9%), 14 (26.9%) pneumonias, 12 (23.1%) bones and joints infections, 10
(19.2%) SSTS, 6 (11.5%) occult bacteremia, 4 (7.7%) meningitis and 2 (3.8%)
sepsis. Surgery was required in 18 cases (34.6%) and 17 patients (32.7%) needed
intensive care. The medium hospital stay was 9.5 days (p25-75: 8-15 days). Three
patients presented sequels and one patient died. CONCLUSION: The ID due to SGA
was a rare but serious reason for hospital admission. Skin and soft tissue
infections, and pleuroneumonia were the most common forms of ID. The mortality of
our sample was low despite the serious clinical manifestations.
PMID- 28705428
TI - Using a pregnancy decision support program for women choosing birth after a
previous caesarean in Japan: A mixed methods study.
AB - BACKGROUND: Opportunities for women and providers to use decision aids and share
decisions about birth after caesarean in practice are currently limited in Japan.
This is despite known benefits of decision aids to support value-sensitive
healthcare decisions. AIM: To explore Japanese women's decision making
experiences using a decision aid program for birth choices after caesarean.
METHODS: A mixed methods study was conducted among 33 consenting pregnant women
with previous caesarean in five obstetrics institutions located in the western
part of Japan. Outcome measures included change in level of decisional conflict,
change in knowledge, and preference for birth method. Semi-structured interviews
examined women's decision making experiences, and qualitative data were analyzed
using thematic analysis. FINDINGS: The participants in the program experienced a
statistically significant improvement in knowledge and reduction in decisional
conflict about birth after caesarean. Four themes were identified in the
qualitative data related to decision making: change in women's knowledge about
birth choices, clarifying women's birth preference, feelings about shared
decision making, and contrasting feelings after receiving information.
DISCUSSION: This study confirmed potential benefits of using the decision aid
program. However, uncertainty about mode of birth continued for some women
immediately prior to the birth. This finding emphasized the need to identify
additional ways to support women emotionally throughout the process of decision
making about birth after caesarean. CONCLUSIONS: It was feasible to adapt the
decision aid for use in clinical practice. Future research is necessary to
examine its effectiveness when implemented in Japanese clinical settings.
PMID- 28705429
TI - Disinfection of Tonometers: A Report by the American Academy of Ophthalmology.
AB - OBJECTIVE: To examine the efficacy of various disinfection methods for reusable
tonometer prisms in eye care and to highlight how disinfectants can damage
tonometer tips and cause subsequent patient harm. METHODS: Literature searches
were conducted last in October 2016 in the PubMed and the Cochrane Library
databases for original research investigations. Reviews, non-English language
articles, nonophthalmology articles, surveys, and case reports were excluded.
RESULTS: The searches initially yielded 64 unique citations. After exclusion
criteria were applied, 10 laboratory studies remained for this review. Nine of
the 10 studies used tonometer prisms and 1 used steel discs. The infectious
agents covered in this assessment include adenovirus 8 and 19, herpes simplex
virus (HSV) 1 and 2, human immunodeficiency virus 1, hepatitis C virus,
enterovirus 70, and variant Creutzfeldt-Jakob disease. All 4 studies of
adenovirus 8 concluded that after sodium hypochlorite (dilute bleach)
disinfection, the virus was undetectable, but only 2 of the 4 studies found that
70% isopropyl alcohol (e.g., alcohol wipes or soaks) eradicated all viable virus.
All 3 HSV studies concluded that both sodium hypochlorite and 70% isopropyl
alcohol eliminated HSV. Ethanol, 70% isopropyl alcohol, dilute bleach, and
mechanical cleaning all lack the ability to remove cellular debris completely,
which is necessary to prevent prion transmission. Therefore, single-use tonometer
tips or disposable tonometer covers should be considered when treating patients
with suspected prion disease. Damage to tonometer prisms can be caused by sodium
hypochlorite, 70% isopropyl alcohol, 3% hydrogen peroxide, ethyl alcohol, water
immersion, ultraviolet light, and heat exposure. Disinfectants can cause
tonometer tips to swell and crack by dissolving the glue that holds the hollow
tip together. The tonometer tip cracks can irritate the cornea, harbor microbes,
or allow disinfectants to enter the interior of the tonometer tip. CONCLUSIONS:
Sodium hypochlorite (dilute bleach) offers effective disinfection against
adenovirus and HSV, the viruses commonly associated with nosocomial outbreaks in
eye care. Tonometer prisms should be examined regularly for signs of damage.
PMID- 28705430
TI - Effect of long-term exposure to air pollution on anxiety and depression in
adults: A cross-sectional study.
AB - BACKGROUND: The association between exposure to air pollutants and mental
disorders among adults has been suggested, although results are not consistent.
OBJECTIVE: To analyze the association between long-term exposure to air pollution
and history of anxiety and depression disorders and of medication use
(benzodiazepines and antidepressants) in adults living in Barcelona. METHODS: A
total of 958 adults (45-74 years old) residents in Barcelona, most of them having
at least one of their parents diagnosed with dementia (86%), and participating in
the ALFA (Alzheimer and Families) study, were included. We used Land Use
Regression (LUR) models to estimate long-term residential exposure (period 2009
2014) to PM2.5, PM2.5 absorbance (PM2.5 abs), PM10, PM coarse, NO2 and NOx.
Between 2013 and 2014 participants self-reported their history of anxiety and
depression disorders and related medication use. The analysis was focused on
those participants reporting outcome occurrence from 2009 onwards (until 2014).
RESULTS: We observed an increased odds of history of depression disorders with
increasing concentrations of all air pollutants [e.g. an increased odds of
depression of 2.00 (95% CI; 1.37, 2.93) for each 10MUg/m3 NO2 increase]. Such
associations were consistent with an increased odds of medication use in relation
to higher concentrations of air pollutants [e.g. an increased odds of
antidepressants use of 1.23 (1.04, 1.44) for each 20MUg/m3 NOx increase].
Associations regarding anxiety disorders did not reach statistical significance.
CONCLUSIONS: Our study shows that increasing long-term exposure to air pollution
may increase the odds of depression and the use of antidepressants and
benzodiazepines. Further studies are needed to replicate our results and confirm
this association.
PMID- 28705431
TI - [Effect of intermittent variable intensity exercise on QT variation and risk of
sudden cardiac death among Cameroonian school adolescents].
AB - INTRODUCTION: Several cases of sudden deaths are observed among students
practicing sport and physical activity (SPA). Just few studies have been carried
out on the variation of the QT (interval) and risk of sudden death during
sporting exercises. AIM: To determine the effect of variable intermittent stress
intensity on the variation of QT and the risk of sudden cardiac death. PATIENTS
AND METHODS: Form 4, lower sixth and upper sixth students were recruited from a
high school in Douala (Cameroon). Each subject was tested; starting with a 2-km
walk followed by a sprint race or an endurance race, protocol I (P1) or the
reverse; protocol II (P2). Two electrocardiograms were recorded; prior to the
beginning of the SPA and 5minutes after the last race. QT was corrected using
four formulas. RESULTS: Forty-one subjects (21 women and 20 men), mean age 18+/-2
years were recruited. At the end of the exercise, corrected QT increased with
Bazzet's formula and decreased with Frahmingam's formula. The difference was not
significant with Fridericia and Hodges formulas. The frequency of long QT was
higher at the end of the exercise with Bazzet's formula (12.2% vs. 24.4%,
P=0.009) while the difference was not significant for the other formulas.
CONCLUSION: The risk of sudden cardiac death increases significantly after SPA.
More studies on large samples are needed.
PMID- 28705432
TI - Identification of galiellalactone-based novel STAT3-selective inhibitors with
cytotoxic activities against triple-negative breast cancer cell lines.
AB - Signal transducer and activator of transcription 3 (STAT3) is phosphorylated in
breast cancer cells, particularly triple-negative breast cancers (TNBCs).
Therefore, the inhibition of constitutive phosphorylated STAT3 is a promising
therapeutic for TNBC treatment. Recently, a series of novel STAT3 inhibitors
based on natural (-)-galiellalactone have been identified to inhibit STAT3
phosphorylation at the Tyr705 residue. Interestingly, the truncation of the
cyclohexene moiety of (-)-galiellalactone to [3.3] bicyclic lactone as a
pharmacophoric core produced improved cytotoxic effects against TNBCs. The potent
analogues 16 and 17, identified from a STAT3-mediated luciferase reporter assay,
selectively inhibited the STAT3 signaling pathway without affecting STAT1 or
STAT5.
PMID- 28705433
TI - Recent advances in racemic protein crystallography.
AB - Solution of the three-dimensional structures of proteins is a critical step in
deciphering the molecular mechanisms of their bioactivities. Among the many
approaches for obtaining protein crystals, racemic protein crystallography has
been developed as a unique method to solve the structures of an increasing number
of proteins. Exploiting unnatural protein enantiomers in crystallization and
resolution, racemic protein crystallography manifests two major advantages that
are 1) to increase the success rate of protein crystallization, and 2) to obviate
the phase problem in X-ray diffraction. The requirement of unnatural protein
enantiomers in racemic protein crystallography necessitates chemical protein
synthesis, which is hitherto accomplished through solid phase peptide synthesis
and chemical ligation reactions. This review highlights the fundamental ideas of
racemic protein crystallography and surveys the harvests in the field of racemic
protein crystallography over the last five years from early 2012 to late 2016.
PMID- 28705435
TI - Resting pectoralis minor muscle length: An accurate way to determine if the
muscle is shortened?
PMID- 28705434
TI - Nanoparticle-macrophage interactions: A balance between clearance and cell
specific targeting.
AB - The surface properties of nanoparticles (NPs) are a major factor that influences
how these nanomaterials interact with biological systems. Interactions between
NPs and macrophages of the reticuloendothelial system (RES) can reduce the
efficacy of NP diagnostics and therapeutics. Traditionally, to limit NP clearance
by the RES system, the NP surface is neutralized with molecules like
poly(ethylene glycol) (PEG) which are known to resist protein adsorption and RES
clearance. Unfortunately, PEG modification is not without drawbacks including
difficulties with the synthesis and associations with immune reactions. To
overcome some of these obstacles, we neutralized the NP surface by acetylation
and compared this modification to PEGylation for RES clearance and tumor-specific
targeting. We found that acetylation was comparable to PEGylation in reducing RES
clearance. Additionally, we found that dendrimer acetylation did not impact folic
acid (FA)-mediated targeting of tumor cells whereas PEG surface modification
reduced the targeting ability of the NP. These results clarify the impact of
different NP surface modifications on RES clearance and cell-specific targeting
and provide insights into the design of more effective NPs.
PMID- 28705436
TI - Non-metric multidimensional performance indicator scaling reveals seasonal and
team dissimilarity within the National Rugby League.
AB - OBJECTIVES: Analysing the dissimilarity of seasonal and team profiles within
elite sport may reveal the evolutionary dynamics of game-play, while highlighting
the similarity of individual team profiles. This study analysed seasonal and team
dissimilarity within the National Rugby League (NRL) between the 2005 to 2016
seasons. DESIGN: Longitudinal. METHODS: Total seasonal values for 15 performance
indicators were collected for every NRL team over the analysed period (n=190
observations). Non-metric multidimensional scaling was used to reveal seasonal
and team dissimilarity. RESULTS: Compared to the 2005 to 2011 seasons, the 2012
to 2016 seasons were in a state of flux, with a relative dissimilarity in the
positioning of team profiles on the ordination surface. There was an abrupt
change in performance indicator characteristics following the 2012 season, with
the 2014 season reflecting a large increase in the total count of 'all run
metres' (d=1.21; 90% CI=0.56-1.83), 'kick return metres' (d=2.99; 90% CI=2.12
3.84) and decrease in 'missed tackles' (d=-2.43; 90% CI=-3.19 to -1.64) and
'tackle breaks' (d=-2.41; 90% CI=-3.17 to -1.62). Interpretation of team
ordination plots showed that certain teams evolved in (dis)similar ways over the
analysed period. CONCLUSIONS: It appears that NRL match-types evolved following
the 2012 season and are in a current state of flux. The modification of coaching
tactics and rule changes may have contributed to these observations. Coaches
could use these results when designing prospective game strategies in the NRL.
PMID- 28705437
TI - GSK-3 signaling in health.
PMID- 28705438
TI - Patients' expectations and preferences regarding cancer follow-up care.
AB - INTRODUCTION: Most survivors of cancer enter a follow-up routine after their
treatment, the aim of which is to detect recurrence, provide psychological
support, monitor treatment-related side-effects, and to evaluate care. Due to
rising numbers of people with cancer and better survival of these patients,
current follow-up routines are under pressure. We reviewed the literature on
patients' expectations and preferences regarding this care. METHODS: We
systematically searched the databases of Pubmed, CINAHL, and PsychInfo. Studies
were screened and data extraction was double performed by three authors. Data
were collected from quantitative and qualitative studies and described
thematically. RESULTS: After screening, 12 full-text articles were included,
comprising 849 patients aged from 28 to 90 years. Patients expect follow-up
visits to detect recurrence of cancer. They want to undergo extensive testing to
get reassurance. Furthermore, patients expect relevant information to be provided
and to get advice about different aspects of their illness. Psychosocial support
is also expected. Patients express a desire for consistency of care as well as
continuity of care, and prefer long and intensive follow-up. DISCUSSION AND
CONCLUSION: After cancer, patients appear to lose confidence in their bodies and
fear cancer recurrence after the end of treatment, which may lead to intensive
screening wishes. This is not desirable, since care for cancer is already under
pressure due to rising numbers of survivors. We have to ensure that follow-up
routines are sustainable and effective. Patients should receive good information
about the need for follow-up tests. Doctors should be trained to give this
information.
PMID- 28705439
TI - Activation of nociceptin/orphanin FQ receptors inhibits contextual fear memory
reconsolidation.
AB - Several neuropeptidergic systems act as modulators of cognitive performances.
Among them, nociceptin, an opioid-like peptide also known as orphanin FQ (N/OFQ),
has recently gained attention. Stimulation of its receptor, the N/OFQ opioid
receptor (NOP), which is expressed in brain regions involved in emotion, memory
and stress response, has inhibitory effects on the acquisition and/or
consolidation of spatial and emotional memory in rodents. Recently, N/OFQ was
also proposed to be linked to the pathogenesis of Post-Traumatic Stress Disorder
in humans. However, until now the effect of the activation of the N/OFQ-NOP
system on already consolidated memory, such as during retrieval and
reconsolidation phases, has never been explored. In the present study, we
investigated the consequences of systemic injection of NOP agonists or i.c.v.
injection of the N/OFQ peptide on the retrieval and the reconsolidation of
contextual fear memory in mice. We demonstrate that the activation of the N/OFQ
system impairs the reconsolidation of context-dependent but not cue-dependent
aversive memories. We also show that this amnestic effect is associated with
decreased c-Fos expression in the hippocampus and amygdala. Our data thus provide
the first evidence that the NOP receptor could be targeted during the
reconsolidation process to weaken maladaptive memories. The N/OFQ-NOP system
might constitute in the future an interesting pharmacological target for
interfering with so-called "pathological memories", in particular those involving
maladaptive contextual memories.
PMID- 28705440
TI - Inhibition of TrkB at the nucleus accumbens, using ANA-12, regulates basal and
stress-induced orexin A expression within the mesolimbic system and affects
anxiety, sociability and motivation.
AB - Repeated stress exposure can lead to the development of anxiety and mood
disorders. An emerging biological substrate of depression and associated
pathology is the nucleus accumbens (NAc), which through interactions with limbic,
cognitive and motor circuits can regulate a variety of stress responses. Within
these circuits, orexin neurons are involved in arousal and stress adaptability,
effects proposed mediated via brain-derived neurotrophic factor signaling. This
study tested the hypotheses that 1) repeated exposure to heterotypic stress
alters social ability and preference and passive avoidant behaviors, 2) TrkB
receptors at the NAc shell regulates stress-induced behavioral responses and
orexin expression within the mesocorticolimbic system. Our findings indicate that
ANA-12 (0.25 MUg/0.5 MUl) enhanced sociability during the social interaction
test, although treatment had no effect on social preference. The development of
conditioned place preference, and fear retention in the passive avoidance test
were also facilitated by ANA-12. Biochemical assessments on brain tissues
collected within 2 h of a forced swim exposure revealed that ANA-12 increased
orexin A immunoreactivity (ir) in the hypothalamic perifornical area, while
expression was reduced in the ventral portion of the hippocampal CA1 layer,
irrespective of the stress condition. This contrasts changes at the VTA
characterized by elevated versus reduced orexin A-ir in ANA-12-treated stress and
non-stress rats, respectively. Colocalized orexin A- and tyrosine hydroxylase
(TH)-ir at the VTA supports a different temporal expression post stress, TH-ir
being unaffected 9 days post stress. These findings support a role for TrkB
receptors in regulating basal and stress-induced social, cognitive and
motivational behavior, and modulatory actions of BDNF, via TrkB signaling, on
orexin A signaling upon stress exposure.
PMID- 28705441
TI - Spin-filtered time-of-flight k-space microscopy of Ir - Towards the "complete"
photoemission experiment.
AB - The combination of momentum microscopy (high resolution imaging of the Fourier
plane) with an imaging spin filter has recently set a benchmark in k-resolution
and spin-detection efficiency. Here we show that the degree of parallelization
can be further increased by time-of-flight energy recording. On the quest towards
maximum information (in earlier work termed "complete" photoemission experiment)
we have studied the prototypical high-Z fcc metal iridium. Large partial bandgaps
and strong spin-orbit interaction lead to a sequence of spin-polarized surface
resonances. Soft X-rays give access to the 4D spectral density function rho
(EB,kx,ky,kz) weighted by the photoemission cross section. The Fermi surface and
all other energy isosurfaces, Fermi velocity distribution vF(kF), electron or
hole conductivity, effective mass and inner potential can be obtained from the
multi-dimensional array rho by simple algorithms. Polarized light reveals the
linear and circular dichroism texture in a simple manner and an imaging spin
filter exposes the spin texture. One-step photoemission calculations are in fair
agreement with experiment. Comparison of the Bloch spectral function with
photoemission calculations uncovers that the observed high spin polarization of
photoelectrons from bulk bands originates from the photoemission step and is not
present in the initial state.
PMID- 28705442
TI - [JMV quite simply].
PMID- 28705443
TI - [Impact of sickle cell trait on arterial stiffness in African subjects].
AB - Sickle cell trait (SCT) is the benign condition of sickle cell disease. Often
asymptomatic, the carriers of the sickle cell trait have hemorheological
disturbances with increased oxidative stress compared to healthy subjects. These
disturbances can lead to structural and functional changes in large vessels. The
aim of the study was to measure arterial stiffness, an independent marker of
subclinical atherosclerosis, SCT carriers compared to sickle cell anemia (SCA)
subjects. Nine SCT carriers aged 32+/-9 years (7 men) were compared to 14 SCA
subjects aged 29+/-9 years (2 men) and 22 control subjects aged 34+/-9 years (11
men) recruited by the National blood transfusion center (CNTS) in Dakar
(Senegal). Arterial stiffness was assessed by measurement of the finger-toe pulse
wave velocity (PWVft) using pOpmetre(r) (Axelife SAS-France). The cardiovascular
risk (CVR) was assessed according to the Framingham Laurier score. The SCT
carriers had a higher PWVft (m/s) than SCA subjects (8.2+/-2.2 vs 6.1+/-0.9m/s,
P=0.004) but not different from that of healthy controls (8.2+/-2.2 vs 7.4+/
1.8m/s, P=0.33). Linear regression showed a positive relationship between PWVft
and the pulse pressure (PP) (P?0.001; r2=0.39; F=13.20). The results show that
the SCT carriers have stiffer arteries than SCA subjects. Linear regressions
adjusted for age, mean arterial pressure (MAP) and PP, showed that only age and
PP were independently correlated with arterial stiffness in the entire
population.
PMID- 28705444
TI - EVAR and OPEN treatment of abdominal aortic aneurysm: What is the role of MMP-9
in the follow-up?
AB - INTRODUCTION: The aim of our study is to verify the role of metalloproteinases in
endovascular repair (EVAR) and OPEN surgery treatment for abdominal aortic
aneurysm (AAA). Postoperatively, these enzymes could represent an important
biomarker to adapt diagnostic tests and further investigations during follow-up.
MATERIAL AND METHOD: From 2004 to 2008, 55 patients were considered with AAA. Of
these, 33 patients (mean age: 70.1 years), (mean AAA diameter: 5.4cm) were
treated with OPEN surgery (group A) and 22 (mean age: 74.1 years) (mean AAA
diameter: 5.1cm) were treated with EVAR. In 17 of them, there were no signs of
endoleak (group B1), while in 5 patients, a presence of endoleak (group B2) was
detected. Plasma samples were collected in order to determine MMP-9 activity.
Enzyme immunoassay was performed preoperatively at 1, 3, 6 and 12 months.
Patients treated conventionally were clinically examined after 1 and 12 months by
ultrasound. Patients undergoing EVAR treatment were clinically examined by CT
scan after 1, 3, 6 and 12 months. The analysis was done by assessing the
interaction over time of the MMP-9 value in B1 and B2 groups. RESULTS: The
average values observed for MMP-9 were preoperatively and at 1, 3, 6 and 12
months, respectively: in group A 150.8ng/mL (SD=30.5), 252.5ng/mL (SD=25.2),
315.4ng/mL (SD=22.7), 295.3ng/mL (SD=26.8), 210.7ng/mL (SD=30.2); in group B1
105ng/mL (SD=10.8), 125.6ng/mL (SD=18), 85.8ng/mL (SD=19.9), 95ng/mL (SD=20.2),
80.4ng/mL (SD=15.6); in group B2 149ng/mL (29.2), 375.4ng/mL (SD=40.2), 215ng/mL
(SD=35.9), 180ng/mL (SD=20.2), 175ng/mL (SD=33.4). The MMP-9 level was higher in
group B2 compared to group B1 (P=0.01), suggesting a correlation with the
presence of the endoleak. CONCLUSIONS: This preliminary study shows that MMP-9
may be a biomarker of the presence of endoleak. Other further investigations and
larger series are needed to show that metalloproteases could play a role in the
follow-up of EVAR treated patients.
PMID- 28705445
TI - [Can bioengineers help predict the risk of aneurysmal rupture?]
PMID- 28705446
TI - A novel sax-stent method in treatment of ascending aorta and aortic arch
aneurysms evaluated by finite element simulations.
AB - OBJECTIVES: A novel stent method to simplify treatment of proximal ascending
aorta and aortic arch aneurysms was developed and investigated by finite element
analysis. Therapy of ascending aortic and aortic arch aneurysms is difficult and
challenging and is associated with various complications. METHODS: A 55mm
wide*120mm long stent was designed without the stent graft and the stent was
deployed by an endovascular method in a virtual patient-specific aneurysm model.
The stress-strain analysis and deployment characteristics were performed in a
finite element analysis using the Abaqus software. RESULTS: The stent, when
embedded in the aortic wall, significantly reduced aortic wall stresses, while
preserving the side coronary ostia and side branches in the aortic arch. When
tissue growth was modeled computationally over the stent struts the wall stresses
in aorta was reduced. This effect became more pronounced when increasing the
thickness of the tissue growth. There were no abnormal stresses in the aorta,
coronary ostium and at the origin of aortic branches. The stent reduced aneurysm
expansion cause by hypertensive condition from 2mm without stenting to 1.3mm
after stenting and embedding. CONCLUSION: In summary, we uncovered a simple
treatment method using a bare nitinol stent without stent graft in the treatment
of the proximal aorta and aortic arch aneurysms, which could eventually replace
the complex treatment methods for this disease.
PMID- 28705447
TI - [Post-traumatic concomitant popliteal artery pseudoaneurysm and arteriovenous
fistula].
AB - Popliteal injuries are well known to be serious with a high rate of mortality due
to damage caused to popliteal vessels. Pseudoaneurysm formation and arteriovenous
fistulas are well-known complications of arterial injury, but are rarely
concomitant. Diagnosis is usually done by computed tomography (CT) angiography.
Treatment strategies consist of surgery or endovascular management. We report the
surgical treatment of two cases of popliteal arteriovenous fistula associated
with pseudoaneurysm complicating stab wounds.
PMID- 28705448
TI - [Extensive digital gangrene revealing late-onset systemic lupus erythematosus].
AB - INTRODUCTION: Late-onset systemic lupus erythematosus represents a specific sub
group of the disorder, beginning after 50 years of age. The incidence is rarer
and the course of the disease is considered to be more benign. Digital gangrene
is an uncommon complication of systemic lupus erythematosus reported especially
among middle-aged patients with long disease duration. OBSERVATION: We report a
53-year-old man, who presented with systemic lupus erythematosus revealed by an
extensive digital gangrene. CONCLUSION: Digital gangrene is a rare complication
of late onset systemic lupus erythematosus. Clinicians should be aware of this
complication in order to initiate early and aggressive treatment.
PMID- 28705449
TI - [Venous thromboembolic disease: Comparison of management practices in France,
Italy and Spain].
AB - BACKGROUND: Many national and international guidelines have been established for
venous thromboembolic disease (VTE). Homogeneous management practices could be
expected in the different European countries. To verify this hypothesis, we
compared practices in France, Italy and Spain. METHOD: We used data from the
international RIETE registry to compare VTE management between France, Italy and
Spain. RESULTS: From 2001 January to 2011 January, patients were consecutively
included in France (n=1548), Italy (n=2083) and Spain (29,824). All patients
received anticoagulant treatment. Low molecular-weight heparin (LMWH) was the
most frequently used drug as initial therapy in all three countries, but
unfractionated heparin (UFH) was more frequently used in France and Italy than in
Spain. In France, the proportion of patients receiving LMWH was lower than the
proportion of patients with active cancer (cancer 22.5 %, long-term treatment
with LMWH 17.4 %). A vena cava filter was significantly more frequently used in
France (5.5 % in France, 3.2 % in Italy and 2 % in Spain, P<0.0001). High
bleeding risk because of surgery with recent thromboembolic disease was the most
frequent indication in France and Italy for vena cava filter placement (36.4 %,
and 31.3 %, respectively). CONCLUSION: Despite the publication of national and
international guidelines, VTE management differs among the three major European
countries included in the RIETE registry, France, Italy and Spain.
PMID- 28705450
TI - Clinical Outcome and Antimicrobial Therapeutic Drug Monitoring for the Treatment
of Infections in Acute Burn Patients.
AB - PURPOSE: In critical burn patients, the pharmacokinetic parameters (absorption,
distribution, metabolism, and excretion) of many classes of drugs, including
antibiotics, are altered. The aim of this study was to compare 2 groups of burn
patients undergoing treatment for health care-associated infections with and
without therapeutic drug monitoring. METHODS: A retrospective analysis of a
clinical intervention (ie, a before/after study) was conducted with patients with
health care-associated pneumonia, burn infection, bloodstream infection, and
urinary tract infection in the burn intensive care unit of a tertiary care
hospital. The patients were divided into 2 groups: (1) those admitted from May
2005 to October 2008 who received conventional antimicrobial dose regimens; and
(2) those admitted from November 2008 to June 2011 who received antibiotics
(imipenem, meropenem, piperacillin, and vancomycin) with doses adjusted according
to plasma monitoring and pharmacokinetic modeling. General characteristics of the
groups were analyzed, as were clinical outcomes and 14-day and in-hospital
mortality. FINDINGS: Sixty-three patients formed the conventional treatment
group, and 77 comprised the monitored treatment group. The groups were
homogeneous, median age was 31 years (range: 1-90) and 66% were male. Improvement
occurred in 60% of the patients under monitored treatment (vs 52% with
conventional treatment); 14-day mortality was 16% vs 14%; and the in-hospital
mortality was similar between groups (39% vs 36%). In the final multivariate
models, variables significantly associated with in-hospital mortality were total
burn surface area >=30%, older age, and male sex. Treatment group did not affect
the prognosis. IMPLICATIONS: Therapeutic drug monitoring of antimicrobial
treatment did not alter the prognosis of these burn patients. More trials are
needed to support the use of therapeutic drug monitoring to optimize treatment in
burn patients.
PMID- 28705451
TI - Nasal Carbon Dioxide Used As Needed in the Symptomatic Treatment of Seasonal
Allergic Rhinitis.
AB - BACKGROUND: Nasal, noninhaled carbon dioxide (CO2) was shown to be effective for
the treatment of symptoms of seasonal allergic rhinitis (SAR) and perennial
allergic rhinitis in single application studies. OBJECTIVE: To assess the
efficacy of as-needed treatment with nasal, noninhaled CO2 in patients with SAR.
METHODS: Fifty-six ragweed-allergic patients were enrolled at 3 sites in this
study. After a 3- to 7-day run-in, 32 eligible patients who had an instantaneous
total nasal symptom score of 8 or more out of a maximum of 12 in at least 2 SAR
episodes per day were randomized to the CO2 group (n = 19) or to the placebo
group (n = 13). A 10-second/nostril application was used as needed for 14 days
(maximum 6 times/d). Patients evaluated their symptoms before and 30 minutes
after each application. All symptoms were scored on a 0 to 3 scale. RESULTS:
Analysis of all treated episodes (CO2 = 816, placebo = 516) showed a
statistically significant beneficial change in total nasal symptom score from
baseline (effect size = -0.51; P < .001). The effect size was larger with more
severe baseline symptoms (baseline severities of >=6 = -0.98; >=8 = -1.14; and
>=10 = -1.61; all P < .001). CO2 was well tolerated, with transient nasal
discomfort as the most common adverse event reported. There were no serious
adverse events, serious adverse device effects, or early discontinuations.
CONCLUSIONS: Nasal, noninhaled CO2 is effective for the as-needed treatment of
SAR symptoms. The effect is rapid and the effect size is large. It represents a
novel potential option for the as-needed treatment of rhinitis symptoms.
PMID- 28705452
TI - Commentary on "Renal Complications After EVAR With Suprarenal Versus Infrarenal
Fixation Among All Users and Routine Users".
PMID- 28705453
TI - Rabbit anti-human-T-lymphocyte globulin-less is more.
PMID- 28705454
TI - Efficacy of two different doses of rabbit anti-T-lymphocyte globulin to prevent
graft-versus-host disease in children with haematological malignancies
transplanted from an unrelated donor: a multicentre, randomised, open-label,
phase 3 trial.
AB - BACKGROUND: Although rabbit anti-T-lymphocyte globulin (ATLG) is largely used for
the prevention of immune-mediated complications in patients given allogeneic
haemopoietic stem-cell transplantation (HSCT) from an unrelated donor, the
optimum dose of this drug in children is still undefined. We aimed to test
whether a higher dose of ATLG was superior to a lower dose for prevention of
grade II-IV acute graft-versus-host disease (GVHD). METHODS: We conducted a
multicentre, randomised, open-label, phase 3 trial in seven Italian centres
comparing two different doses of ATLG (30 mg/kg vs 15 mg/kg, given intravenously
over 3 days, from day -4 to -2) in children (aged 0-18 years) with haematological
malignancies transplanted from an unrelated donor, selected using high-resolution
typing for HLA-class I/II loci. All patients received a myeloablative regimen and
cyclosporine-A plus short-term methotrexate as post-transplantation GVHD
prophylaxis. Patients were randomly assigned (1:1) to either of the two groups
and were stratified by the degree of HLA-compatibility with their donor, the
source of haemopoietic stem cells used (bone marrow vs peripheral blood stem
cells), and the disease risk category. The randomisation was open label; all
investigators were aware of the treatment allocation. The primary endpoint of the
study was 100-day cumulative incidence of grade II-IV acute GVHD. Statistical
analyses were done according to the per-protocol principle. Other outcomes
included cumulative incidence of chronic GVHD, non-relapse mortality, disease
recurrence, and probability of overall survival and event-free survival. This
study was registered with ClinicalTrials.gov, number NCT00934557. FINDINGS:
Between Jan 15, 2008, and Sept 25, 2012, 89 patients were randomly assigned to
the 30 mg/kg ATLG group and 91 to the 15 mg/kg ATLG group; 84 patients in the 30
mg/kg ATLG group and 88 in the 15 mg/kg ATLG group were included in the analysis.
The median follow-up for the whole study population was 3.4 years (IQR 1.7-5.1).
The 100-day cumulative incidence of grade II-IV acute GVHD was 36% (95% CI 28-48)
in the 15 mg/kg ATLG group and 29% (20-40) in the 30 mg/kg ATLG group (hazard
ratio [HR] 0.74, 95% CI 0.44-1.25; p=0.26). The cumulative incidence of non
relapse mortality was 9% (5-18) in the 15 mg/kg ATLG group and 19% (12-30) in the
30 mg/kg ATLG group (HR 2.08, 0.89-4.96; p=0.092). Cumulative incidence of
disease recurrence was 15% (12-24): 14% (8-23) in the 15 mg/kg ATLG group versus
20% (13-31) in the 30 mg/kg ATLG group (HR 1.54, 0.74-3.21; p=0.25). The 5-year
overall survival probability was 70% (62-77) for the whole study population: 78%
(69-87) in the 15 mg/kg ATLG group versus 62% (50-73) in the 30 mg/kg ATLG group
(HR 1.80, 1.01-3.20; p=0.045). The 5-year event-free survival was 77% for
children in the 15 mg/kg ATLG group versus 61% in the 30 mg/kg ATLG group (HR
1.87, 1.07-3.28; p=0.028). INTERPRETATION: Children with haematological
malignancies transplanted from unrelated donors selected through high-resolution
HLA-typing benefit from the use of a 15 mg/kg ATLG dose in comparison with a 30
mg/kg ATLG dose. ATLG at 15 mg/kg should thus be regarded as the standard
serotherapy regimen for unrelated donor allogeneic HSCT in this patient
population. Future randomised studies will continue to aim to optimise patient
outcome and strategies to prevent acute GVHD occurrence. FUNDING:
Fresenius/Neovii Biotech.
PMID- 28705455
TI - A molecular phylogeny of the Pacific clade of Cyrtandra (Gesneriaceae) reveals a
Fijian origin, recent diversification, and the importance of founder events.
AB - Cyrtandra (Gesneriaceae) is among the largest genera of flowering plants in the
remote oceanic islands of the Pacific, with an estimated 175 species distributed
across an area that extends from the Solomon Islands, east to the Marquesas
Islands, and north to the Hawaiian Islands. The vast majority of species are
single-island endemics that inhabit upland rainforests. Although previous
molecular phylogenetic studies greatly advanced our understanding of the
diversification of Pacific Cyrtandra, a number of uncertainties remain regarding
phylogenetic relationships, divergence times, and biogeographic patterns within
this large and widely dispersed group. In the present study, five loci (ITS, ETS,
Cyrt1, psbA-trnH, and rpl32-trnL) were amplified and sequenced for phylogenetic
reconstruction of 121 Cyrtandra taxa. Maximum likelihood and Bayesian inference
confirmed that C. taviunensis from Fiji is sister to the remaining members of the
Pacific clade. Dating analyses and ancestral area estimation indicates that the
Pacific clade of Cyrtandra originated in Fiji during the Miocene ca. 9mya. All
major crown lineages within the Pacific clade appeared < 5mya, coincident with
the emergence of numerous Pacific islands and a subsequent increase in available
habitat. The biogeographic history of Cyrtandra in the Pacific has been shaped by
extinction, dispersal distance, and founder events. Biogeographic stochastic
mapping analyses suggest that cladogenesis within Pacific Cyrtandra involved a
combination of narrow (within-area) sympatry and founder events. A mean of 24
founder events was recovered between Pacific archipelagos, while a mean of 10
founder events was recovered within the Hawaiian archipelago.
PMID- 28705456
TI - Feeling touch on the own hand restores the capacity to visually discriminate it
from someone else' hand: Pathological embodiment receding in brain-damaged
patients.
AB - The sense of body ownership, i.e., the belief that a specific body part belongs
to us, can be selectively impaired in brain-damaged patients. Recently, a
pathological form of embodiment has been described in patients who, when the
examiner's hand is located in a body-congruent position, systematically claim
that it is their own hand (E+ patients). This paradoxical behavior suggests that,
in these patients, the altered sense of body ownership also affects their
capacity of visually discriminating the body-identity details of the own and the
alien hand, even when both hands are clearly visible on the table. Here, we
investigated whether, in E+ patients with spared tactile sensibility, a coherent
body ownership could be restored by introducing a multisensory conflict between
what the patients feel on the own hand and what they see on the alien hand. To
this aim, we asked the patients to rate their sense of body ownership over the
alien hand, either after segregated tactile stimulations of the own hand (out of
view) and of the alien hand (visible) or after synchronous and asynchronous
tactile stimulations of both hands, as in the rubber hand illusion set-up. Our
results show that, when the tactile sensation perceived on the patient's own hand
was in conflict with visual stimuli observed on the examiner's hand, E+ patients
noticed the conflict and spontaneously described visual details of the (visible)
examiner's hand (e.g., the fingers length, the nails shape, the skin color...),
to conclude that it was not their own hand. These data represent the first
evidence that, in E+ patients, an incongruent visual-tactile stimulation of the
own and of the alien hand reduces, at least transitorily, the delusional body
ownership over the alien hand, by restoring the access to the perceptual self
identity system, where visual body identity details are stored.
PMID- 28705457
TI - A novel C-type lectin gene is a strong candidate gene for Benedenia disease
resistance in Japanese yellowtail, Seriola quinqueradiata.
AB - Little is known about mechanisms of resistance to parasitic diseases in marine
finfish. Benedenia disease is caused by infection by the monogenean parasite
Benedenia seriolae. Previous quantitative trait locus (QTL) analyses have
identified a major QTL associated with resistance to Benedenia disease in linkage
group Squ2 of the Japanese yellowtail/amberjack Seriola quinqueradiata. To
uncover the bioregulatory mechanism of Benedenia disease resistance, complete
Illumina sequencing of BAC clones carrying genomic DNA for the QTL region in
linkage group Squ2 was performed to reveal a novel C-type lectin in this region.
Expression of the mRNA of this C-type lectin was detected in skin tissue
parasitized by B. seriolae. Scanning for single nucleotide polymorphisms (SNPs)
uncovered a SNP in the C-type lectin/C-type lectin-like domain that was
significantly associated with B. seriolae infection levels. These results
strongly suggest that the novel C-type lectin gene controls resistance to
Benedenia disease in Japanese yellowtails.
PMID- 28705458
TI - Insulin resistance and elevated C-reactive protein among first-degree relatives
of ischemic stroke patients.
AB - BACKGROUND: Family history is one of the non-modifiable risk factors for ischemic
stroke. Atherosclerosis and thrombosis are the two major mechanisms for
cardiovascular disease and stroke. Screening of family members is an important
method to identify individuals at risk. Therefore, this study was planned to
assess the atherosclerotic risk factors in first-degree relatives of patients
with ischemic stroke. METHODOLOGY: Case group included 40 first-degree relatives
of ischemic stroke patients between 30 and 50 years of age. Forty age and gender
matched apparently healthy subjects without major risk factors were recruited as
controls. Their blood samples were analysed for routine biochemical parameters,
Fasting Insulin, high sensitivity C-reactive protein and Homocysteine. RESULTS:
First-degree relatives showed dyslipidemia (High total cholesterol, elevated Low
Density Lipoprotein and elevated Non-High Density Lipoprotein), hyperinsulinemia
and insulin resistance compared to controls. They had high levels of high
sensitivity C-reactive protein (p=0.045). There was positive correlation between
fasting insulin and Homeostasis Model Assessment of Insulin Resistance with high
sensitivity C-reactive protein among first-degree relatives. CONCLUSION: First
degree relatives of ischemic stroke patients exhibited hyperinsulinemia, Insulin
resistance and dyslipidemia. Insulin resistance, a low grade inflammatory state
that leads to increased C-reactive protein which triggers the development of
atherosclerosis. So screening for insulin resistance and dyslipidemia in first
degree relatives of ischemic stroke patients may help in preventing adverse
vascular events.
PMID- 28705459
TI - Pre-stroke glycemia in patients with diabetes.
AB - AIMS: Hyperglycemia in type 2 diabetes mellitus (T2D) remains uncontrolled in
approximately 50% of patients in the United States. Uncontrolled T2D is
associated with various vascular complications, including stroke. We studied
demographic and clinical factors association with pre-stroke glycemia, indicated
by glycated hemoglobin (HbA1c), in acute stroke patients with T2D. METHODS: Using
a questionnaire, we collected demographic, socioeconomic, and clinical
information from 300 acute ischemic and hemorrhagic stroke patients in one
hospital. We analyzed factors associated with HbA1c in patients with history of
T2D. RESULTS: There were 111 patients with history of T2D and HbA1c measured on
admission. In multivariable analyses factors associated with higher HbA1c were
treatment with insulin (p=0.05), history of hyperlipidemia (p=0.01), and total
cholesterol level (p=0.02). Poor adherence to T2D treatment was associated with
higher HbA1c levels (p=0.006) only in a subgroup of patients with HbA1c >=8%.
CONCLUSION: Insulin treatment and hyperlipidemia are associated with higher HbA1c
levels in acute stroke patients with T2D. Poor adherence to diabetes treatment is
associated with higher HbA1c levels only among patients with HbA1c >=8%.
PMID- 28705460
TI - Global hearing health care: new findings and perspectives.
AB - In 2015, approximately half a billion people had disabling hearing loss, about
6.8% of the world's population. These numbers are substantially higher than
estimates published before 2013, and point to the growing importance of hearing
loss and global hearing health care. In this Review, we describe the burden of
hearing loss and offer our and others' recommendations for halting and then
reversing the continuing increases in this burden. Low-cost possibilities exist
for prevention of hearing loss, as do unprecedented opportunities to reduce the
generally high treatment costs. These possibilities and opportunities could and
should be exploited. Additionally, a comprehensive worldwide initiative like
VISION 2020 but for hearing could provide a focus for support and also enable and
facilitate the increased efforts that are needed to reduce the burden. Success
would produce major personal and societal gains, including gains that would help
to fulfil the "healthy lives" and "disability inclusive" goals in the UN's new
2030 Agenda for Sustainable Development.
PMID- 28705461
TI - Gonorrhoea vaccines: a step in the right direction.
PMID- 28705462
TI - Effectiveness of a group B outer membrane vesicle meningococcal vaccine against
gonorrhoea in New Zealand: a retrospective case-control study.
AB - BACKGROUND: Gonorrhoea is a major global public health problem that is
exacerbated by drug resistance. Effective vaccine development has been
unsuccessful, but surveillance data suggest that outer membrane vesicle
meningococcal group B vaccines affect the incidence of gonorrhoea. We assessed
vaccine effectiveness of the outer membrane vesicle meningococcal B vaccine
(MeNZB) against gonorrhoea in young adults aged 15-30 years in New Zealand.
METHODS: We did a retrospective case-control study of patients at sexual health
clinics aged 15-30 years who were born between Jan 1, 1984, and Dec 31, 1998,
eligible to receive MeNZB, and diagnosed with gonorrhoea or chlamydia, or both.
Demographic data, sexual health clinic data, and National Immunisation Register
data were linked via patients' unique personal identifier. For primary analysis,
cases were confirmed by laboratory isolation or detection of Neisseria
gonorrhoeae only from a clinical specimen, and controls were individuals with a
positive chlamydia test only. We estimated odds ratios (ORs) comparing disease
outcomes in vaccinated versus unvaccinated participants via multivariable
logistic regression. Vaccine effectiveness was calculated as 100*(1-OR).
FINDINGS: 11 of 24 clinics nationally provided records. There were 14 730 cases
and controls for analyses: 1241 incidences of gonorrhoea, 12 487 incidences of
chlamydia, and 1002 incidences of co-infection. Vaccinated individuals were
significantly less likely to be cases than controls (511 [41%] vs 6424 [51%];
adjusted OR 0.69 [95% CI 0.61-0.79]; p<0.0001). Estimate vaccine effectiveness of
MeNZB against gonorrhoea after adjustment for ethnicity, deprivation,
geographical area, and sex was 31% (95% CI 21-39). INTERPRETATION: Exposure to
MeNZB was associated with reduced rates of gonorrhoea diagnosis, the first time a
vaccine has shown any protection against gonorrhoea. These results provide a
proof of principle that can inform prospective vaccine development not only for
gonorrhoea but also for meningococcal vaccines. FUNDING: GSK Vaccines.
PMID- 28705463
TI - Department of Error.
PMID- 28705465
TI - Vitamin D, body composition, and epicardial adipose tissue.
PMID- 28705464
TI - Diversity of Pneumocystis jirovecii Across Europe: A Multicentre Observational
Study.
AB - Pneumocystis jirovecii is an airborne human-specific ascomycetous fungus
responsible for Pneumocystis pneumonia (PCP) in immunocompromised patients,
affecting >500,000 patients per year (www.gaffi.org). The understanding of its
epidemiology is limited by the lack of standardised culture. Recent genotyping
data suggests a limited genetic diversity of P. jirovecii. The objective of the
study was to assess the diversity of P. jirovecii across European hospitals and
analyse P. jirovecii diversity in respect to clinical data obtained from the
patients. Genotyping was performed using six already validated short tandem
repeat (STR) markers on 249 samples (median: 17 per centre interquartile range
[11-20]) from PCP patients of 16 European centres. Mixtures of STR markers (i.e.,
>=2 alleles for >=1 locus) were detected in 67.6% (interquartile range [61.4;
76.5]) of the samples. Mixture was significantly associated with the underlying
disease of the patient, with an increased proportion in HIV patients (78.3%) and
a decreased proportion in renal transplant recipients (33.3%) (p<0.001). The
distribution of the alleles was significantly different (p<0.001) according to
the centres in three out of six markers. In analysable samples, 201 combinations
were observed corresponding to 137 genotypes: 116 genotypes were country
specific; 12 in two; six in three; and two in four and one in five countries.
Nine genotypes were recorded more than once in a given country. Genotype 123
(Gt123) was significantly associated with France (14/15, p<0.001) and Gt16 with
Belgium (5/5, p<0.001). More specifically, Gt123 was observed mainly in France
(14/15/16 patients) and in renal transplant patient (13/15). Our study showed the
wide population diversity across Europe, with evidence of local clusters of
patients harbouring a given genotype. These data suggest a specific association
between genotype and underlying disease, with evidence of a different natural
history of PCP in HIV patients and renal transplant recipients.
PMID- 28705466
TI - Serum folic acid levels are associated with the presence and severity of liver
steatosis in Chinese adults.
AB - BACKGROUND & AIMS: Non-alcoholic fatty liver disease (NAFLD) is a common and
strong risk factor for cardiovascular disease and hepatocellular carcinoma. The
rapid acceleration of the increase in NAFLD prevalence has exceeded the trends
observed for obesity, and has been driven by multiple factors. The aim of this
study was to investigate the correlation between the serum levels of folic acid,
the endogenous source of methyl groups for DNA methylation, and NAFLD in Chinese
adults. METHODS: The correlations between the serum folic acid levels and NAFLD
were investigated in two independent cohorts of 70 subjects who underwent a liver
biopsy and 130 subjects with varying liver fat contents, as measured using proton
magnetic resonance spectroscopy (1H-MRS). Independent correlations between serum
folic acid levels and liver steatosis grades were detected using a multivariate
ordinal regression analysis. The diagnostic performances of serum folic acid
levels alone and in combination with existing NAFLD prediction scores were
compared with those of traditional NAFLD prediction parameters using receiver
operating characteristic (ROC) curve analyses. RESULTS: Serum folic acid
concentrations were inversely correlated with liver histological steatosis grades
(rho = -0.371, P < 0.001) and the 1H-MRS-measured liver fat content (r = -0.199,
P = 0.038). According to the multivariate ordinal regression analysis, serum
folic acid levels were inversely correlated with liver steatosis grades (OR 0.739
[0.594-0.918], P = 0.006) independent of age, gender, BMI, components of
metabolic syndrome and the serum TC, LDL-c and HOMA-IR levels. The AUROC of serum
folic acid for the diagnosis of NAFLD was 0.75 (0.65-0.83), and the addition of
serum folic acid to NAFLD prediction scores significantly improved the diagnostic
prediction of NAFLD (AUROC = 0.88 [0.81-0.94]). CONCLUSION: Low serum folic acid
levels were identified as an independent risk factor for NAFLD in the Chinese
population. The addition of the serum folic acid levels to the current existing
NAFLD prediction scores significantly improved the prediction of NAFLD.
PMID- 28705467
TI - Sarcoidosis with fever and a splenic infarct due to CMV or lymphoma?
AB - We present a case of an adult female with a past history of pulmonary sarcoidosis
who presented with fever, night sweats, profound fatigue, and LUQ abdominal pain.
Sarcoidosis is an afebrile disorder (excluding Lofgren's syndrome, Heerfordt's
syndrome or neurosarcoidosis). Therefore, the presence of fever with sarcoidosis
should suggest infection, usually viral, or lymphoma. Sarcoidosis-lymphoma
syndrome describes the evolution of a lymphoma in long standing sarcoidosis.
Fever aside, possible lymphoma is suggested by otherwise unexplained fever,
pleural unilateral effusion, highly elevated ESR or ferritin levels. In this
case, a viral etiology was suggested because of atypical lymphocytosis and mildly
elevated transaminases. In this patient, CMV IgM titers and elevated CMV PCR
viral load confirmed the diagnosis of CMV infectious mononucleosis with lung and
liver involvement. In this case CMV infectious mononucleosis was accompanied by
procoagulant activity which resulted a DVT, pulmonary emboli and splenic infarct.
We believe this to be the first reported case of CMV infectious mononucleosis
splenic infarct in a patient with a history of sarcoidosis.
PMID- 28705468
TI - Association of anti-inflammatory cytokine IL10 polymorphisms with motoric
cognitive risk syndrome in an Ashkenazi Jewish population.
AB - Motoric cognitive risk (MCR) syndrome is a newly described predementia syndrome
characterized by the presence of cognitive complaints and slow gait, which is
associated with increased risk of conversion to dementia. The underlying
biological mechanisms for MCR have not yet been established. Neuroinflammation
mediated through cytokines plays a pivotal role in the pathogenesis of dementia.
Hence, our objective was to prospectively examine whether variations in cytokine
genes (CRP, IFNG, IL1A, IL1B, IL4, IL6, IL10, IL18, TNF, and IL12A) play a role
in MCR incidence in 530 community-dwelling Ashkenazi Jewish adults aged 65 years
and older without MCR or dementia at baseline enrolled in the LonGenity study.
Over a median follow-up of 2.99 years, 70 participants developed MCR. Single
nucleotide polymorphisms (SNPs) in the transcriptional regulatory regions of
cytokine IL10, rs1800896 (hazard ratio adjusted for age, gender, and education,
aHR: 1.667; 95% CI: 1.198-2.321) and rs3024498 (aHR: 1.926; 95% CI: 1.315-2.822),
were associated with incident MCR. Functional analysis using in silico approaches
indicated associated SNP rs3024498 "C" allele being the local expression
quantitative trait locus. Associated alleles of both the SNPs, rs1800896 and
rs3024498, were implicated with overexpression of IL10 gene. None of the variants
in the neuroinflammatory pathway studied were associated with incident mild
cognitive impairment syndrome. These observations support a role for the IL10
gene in dementia pathogenesis by increasing risk of developing MCR in older
adults.
PMID- 28705469
TI - Systematic prioritization of functional hotspot in RIG-1 domains using pattern
based conventional molecular dynamic simulation.
AB - BACKGROUND: Retinoic acid inducible gene 1 (RIG-1), multi-domain protein has a
role-play in detecting viral nucleic acids and stimulates the antiviral response.
Dysfunction of this protein due to mutations makes the route vulnerable to viral
diseases. AIM: Identification of functional hotspots that maintains
conformational stability in RIG-1 domains. METHODS: In this study, we employed a
systematic in silico strategy on RIG-1 protein to understand the mechanism of
structural changes upon mutation. We computationally investigated the protein
sequence signature for all the three domains of RIG-1 protein that encloses the
mutation within the motif. Further, we carried out a structural comparison
between RIG-1 domains with their respective distant orthologs which revealed the
minimal number of interactions required to maintain its structural fold. This
intra-protein network paved the way to infer hotspot residues crucial for the
maintenance of the structural architecture and folding pattern. KEY FINDINGS: Our
analysis revealed about 40 hotspot residues that determine the folding pattern of
the RIG-1 domains. Also, conventional molecular dynamic simulation coupled with
essential dynamics provides conformational transitions of hot spot residues among
native and mutant structures. Structural variations owing to hotspot residues in
mutants again confirm the significance of these residues in structural
characterization of RIG-1 domains. We believe our results will help the
researchers to better comprehend towards regulatory regions and target-binding
sites for therapeutic design within the pattern recognition receptor proteins.
SIGNIFICANCE: Our protocol employed in this work describes a novel approach in
identifying signature residues that would provide structural insights in protein
folding.
PMID- 28705470
TI - Hypoxia and hypoxia response-associated molecular markers in esophageal cancer: A
systematic review.
AB - PURPOSE: In this systematic review, the existing evidence of available hypoxia
associated molecular response biomarkers in esophageal cancer (EC) patients is
summarized and set into the context of the role of hypoxia in the prediction of
esophageal cancer, treatment response and treatment outcome. METHODS: A
systematic literature search was performed in Web of Science, MEDLINE, and PubMed
databases using the keywords: hypoxia, esophagus, cancer, treatment outcome and
treatment response. Eligible publications were independently evaluated by two
reviewers. In total, 22 out of 419 records were included for systematic review.
The described search strategy was applied weekly, with the last update being
performed on April 3rd, 2017. RESULTS: In esophageal cancer, several (non
)invasive biomarkers for hypoxia could be identified. Independent prognostic
factors for treatment response include HIF-1alpha, CA IX, GLUT-1 overexpression
and elevated uptake of the PET-tracer 18F-fluoroerythronitroimidazole (18F
FETNIM). Hypoxia-associated molecular responses represents a clinically relevant
phenomenon in esophageal cancer and detection of elevated levels of hypoxia
associated biomarkers and tends to be associated with poor treatment outcome
(i.e., overall survival, disease-free survival, complete response and local
control). CONCLUSION: Evaluation of tumor micro-environmental conditions, such as
intratumoral hypoxia, is important to predict treatment outcome and efficacy.
Promising non-invasive imaging-techniques have been suggested to assess tumor
hypoxia and hypoxia-associated molecular responses. However, extensive validation
in EC is lacking. Hypoxia-associated markers that are independent prognostic
factors could potentially provide targets for novel treatment strategies to
improve treatment outcome. For personalized hypoxia-guided treatment, safe and
reliable makers for tumor hypoxia are needed to select suitable patients.
PMID- 28705471
TI - Risk assessment and serotonin: Animal models and human psychopathologies.
AB - Risk assessment (RA) is an evolved, generally adaptive, mechanism comprising
focused attention and appraisal of potential threat stimuli and situations.
Initially characterized in animal models, it provides a number of behavioral and
functional parallels to patterns of rumination, gaze biases, and other forms of
affective cognition that appear to be disregulated in depression and anxiety.
Serotonergic mechanisms are involved in these mood disorders, and an emerging
body of evidence suggests that they may modulate the affective cognitive changes
common to such psychopathologies. Findings of parallel effects of serotonin
systems in RA would support a view that it may provide a useful behavioral
endophenotype for translational research on mood disorders. This review examines
the involvement of serotonergic mechanisms in both animal models of RA, and in an
array of tasks focusing on affective cognitive changes in individuals with
depression or anxiety. Results suggest substantial serotonin involvement in both
RA behaviors measured in rats or mice, and in the "intersection of emotional and
cognitive processes" [43] in people.
PMID- 28705472
TI - Adolescent social isolation affects schizophrenia-like behavior and astrocyte
biomarkers in the PFC of adult rats.
AB - Social isolation is regarded as a cause of schizophrenia spectrum disorders.
Animal models of schizophrenia are constructed by repeated early environment
deprivation as an important paradigm to reveal its pathological mechanism. Male
Sprague Dawley rats were assigned to either social-rearing (SR) or isolated
rearing (IR) groups during postnatal days (PNDs) 21-34. On PND 56, all rats
underwent behavioral testing including locomotor activity, anxiety-related
behaviors in an open field and prepulse inhibition (PPI). Then, the rats were
sacrificed and prefrontal cortex (PFC) tissues were separated for high-throughput
proteomics analysis and Western blot validation. Rats of the IR group showed
increased spontaneous locomotion, increased anxiety-like behavior and disrupted
PPI compared with rats of the SR group. Based on proteomics analysis, a total of
124 PFC proteins were found to be significantly differentially expressed between
the SR group and the IR group, the most remarkable of which were glial fibrillary
acidic protein (GFAP), Annexin A2 (ANXA2) and vimentin (VIM), three astrocyte
biomarkers. Further Western blot measurement confirmed that the levels of GFAP,
ANXA2 and VIM were increased significantly in IR rats. Adolescent social
isolation induced schizophrenia-like behaviors and significantly different
expression of 124 PFC proteins in adult rats, especially GFAP, ANXA2 and VIM,
which suggests that astrocyte development might be involved in the neural
mechanism of schizophrenia.
PMID- 28705473
TI - Deal or no deal? The prevalence and nutritional quality of price promotions among
U.S. food and beverage purchases.
AB - OBJECTIVE: This study examines trends in the prevalence of price promotions among
packaged food and beverage purchases, differences in prevalence by household
race/ethnicity or income, and the association between price promotions and the
nutritional profile of purchases. DESIGN: This cross-sectional study utilizes a
dataset of 90 million purchases from 38,744 (2008) to 45,042 (2012) US households
in 2008-2012. Chi-square tests were used to examine whether the proportion of
purchases with price promotions changed over time or differed by household
race/ethnicity or income. T-tests were used to compare purchased products'
nutritional profiles. RESULTS: Prevalence of price promotions among packaged food
and beverage purchases increased by 8% and 6%, respectively, from 2008 to 2012,
with both reaching 34% by 2012. Higher-income households had greater proportions
of purchases with price promotions than lower-income households. Asian households
had the highest proportion of purchases with any price promotion, followed by non
Hispanic whites. While total price-promoted packaged food purchases had higher
mean energy, total sugar, and saturated fat densities than purchases with no
price promotions, absolute differences were small. CONCLUSIONS: Prevalence of
price promotions among US household purchases increased from 2008 to 2012 and was
greater for higher-income households. No clear associations emerged between
presence of price promotions and nutritional quality of purchases.
PMID- 28705474
TI - RF-ablation in periventricular heterotopia-related epilepsy.
AB - Drug-resistant focal epilepsy is a common occurrence in patients with gray matter
nodular heterotopia (NH), and surgical treatment is often considered in these
cases. NH-related epileptogenicity is sustained by complex networks, which may
involve the nodules and extralesional cortex in various combinations. Therefore,
invasive EEG is usually required to identify the structures involved in seizure
generation. It has been reported that surgery may be effective in cases with
unilateral lesions, whereas bilateral cases are not optimal candidates for
surgical success. Furthermore, violation of cortical and subcortical structures
for approaching deep-seated nodules may result in neurological deficits. For
these reasons, selective stereotactic ablation with radiofrequency
thermocoagulation (RFTC) has been proposed as an alternative option in these
patients. In particular, RFTC may be performed by using the same recording
intracerebral electrodes implanted for stereo-electro-encephalo-graphy (SEEG)
monitoring, with the advantage of a reliable electro-clinical guide. Excellent
results on seizures have been initially reported following coagulation of single,
unilateral NH. Subsequent experience has indicated that, basing on the evidence
of SEEG recording, promising results may be obtained also in more extended
unilateral and bilateral cases. In more complex cases, coagulation of both the
nodules and of the involved extralesional cortical structures is often required.
In a recently reported series, 67% of patients experienced sustained seizure
freedom after the procedure. However, post RFTC seizure outcome in complex cases
(NH plus other malformations of cortical development) is not as good as in other
patterns of NH. RFTC, especially if guided by SEEG evaluation, should be
considered as a first-line treatment option in NH-related epilepsy. Satisfactory
results may be obtained also in cases not amenable to traditional surgery. The
procedure is safe and does not prevent eventual resective surgery in case of
failure in seizure control. For these reasons, in patients undergoing SEEG
evaluation, electrode arrangement should be planned with the aim to cover as
extensively as possible the heterotopic and extralesional areas, which will
presumably be the targets of RFTC.
PMID- 28705475
TI - Molecular alterations in signal pathways of melanoma and new personalized
treatment strategies: Targeting of Notch.
AB - Despite modern achievements in therapy of malignant melanomas new treatment
strategies are welcomed in clinics for survival of patients. Now it is supposed
that personalized molecular therapies for each patient are needed concerning a
specificity of molecular alterations in patient's tumors. In human melanoma,
Notch signaling interacts with other pathways, including MAPK, PI3K-AKT, NF-kB,
and p53. This article discusses mutated genes and leading aberrant signal
pathways in human melanoma which are of interest concerning to their perspective
for personalized treatment strategies in melanoma. We speculate that E3 ubiquitin
ligases MDM2 and MDM4 can be attractive therapeutic target for p53 and Notch
signaling pathways in malignant melanoma by using small molecule inhibitors. It
is possible that restoration of p53-MDM2-NUMB complexes in melanoma can restore
wild type p53 function and positively modulate Notch pathway. In this review we
summarize recent data about novel US Food and Drug Administration approved target
drugs for metastatic melanoma treatment, and suppose model for treatment strategy
by targeting Notch.
PMID- 28705476
TI - Long-term follow-up of children with typical hemolytic uremic syndrome.
AB - OBJECTIVE: The aim of the study was to determine the associations of the acute
period course with late-emerging sequelae in children with typical hemolytic
uremic syndrome (HUS). MATERIALS AND METHODS: The data of 62 children with
typical HUS during the acute phase were retrospectively analyzed by age, sex,
duration of anuria/oliguria, method and duration of renal replacement therapy,
proteinuria, hypertension, and renal function. The data of 33 children at 10-year
follow-up after the onset of the disease were evaluated for changes in
hypertension, proteinuria, and renal function. RESULTS: In the acute phase of the
disease (n=62), hypertension was documented in 75.8% of the children;
proteinuria, in 85.5%; and renal dysfunction, in 100%. At 10 years after the
onset of the disease (n=33), hypertension was documented in 12.1%, 6.1%, and
24.2% at 1-, 5-, and >=10-year follow-ups, respectively, and more often in
children aged <1 year at the onset of the disease. Proteinuria was found in
15.2%, 9.1%, and 33.3% of the patients, respectively. After >=10 years,
hypertension developed for the first time in 6.1% of the patients. Renal injury
of varying degrees was seen in 15.2% of the children at the 1-year follow-up, and
after >=10 years the proportion increased to 33.3%. CONCLUSIONS: At 10 years
after the acute phase of typical HUS in children, the prevalence of hypertension
and proteinuria at 1- and 5-year follow-ups decreased, but after 10 years it
started to increase. As much as 6.1% of the children developed hypertension or
proteinuria for the first time at 10 years. Hypertension was documented more
frequently in children who were younger than <1 year at the onset of the disease.
Renal dysfunction after 5 and 10 years remained in more than one-third of cases,
and it was observed more often if hypertension was documented at the acute
period.
PMID- 28705477
TI - Association of cardio-ankle vascular index with cardiovascular risk factors and
cardiovascular events in metabolic syndrome patients.
AB - OBJECTIVES: We aimed to investigate the association between arterial stiffness
assessed as cardio-ankle vascular index (CAVI) and cardiovascular (CV) risk
factors and CV events in the middle-aged metabolic syndrome (MS) patients.
MATERIALS AND METHODS: A follow-up study was carried out in 2106 middle-aged
(53.83+/-6.17 years old, 62% women) MS subjects without overt atherosclerotic
disease. Patients were initially recruited in 2009-2011 as participants of the
Lithuanian High Cardiovascular Risk (LitHiR) primary prevention program and
followed up for 3.8+/-1.7 years for CV events. Thorough cardiometabolic risk
assessment was carried out at inclusion. RESULTS: Subjects with higher CAVI had
worse lipid and glucose metabolism profile: elevated total cholesterol (TC) and
low-density lipoprotein cholesterol (LDL-C), decreased high-density lipoprotein
cholesterol (HDL-C), higher fasting and oral glucose tolerance test (OGTT)
glucose levels (all P<0.001), and lower fasting insulin (P=0.021). Greater age
(P<0.001), heart rate (P=0.016), and mean arterial pressure (P<0.001) were also
associated with higher CAVI. Over the follow-up period, 93 (4.4%) patients
developed a cardiovascular event: 55 (2.6%) patients had myocardial infarction
and 38 (1.8%) suffered a cerebrovascular event. Fatal CV events comprised 6.5%
(n=6) of all CV events. CAVI was statistically significantly associated with
occurrence of myocardial infarction (P=0.027) and total cardiovascular events
(P=0.045), but not cerebrovascular events (P=0.65). However, this association was
dependent on age and gender. CONCLUSIONS: In the middle-aged MS patients, higher
CAVI was associated with altered lipid and glucose metabolism, older age, greater
heart rate and mean arterial pressure, and worse cardiovascular outcome.
PMID- 28705478
TI - Increased innate and adaptive immune responses in induced sputum of young
smokers.
AB - BACKGROUND AND OBJECTIVES: It is known that chronic obstructive pulmonary disease
(COPD) development process is imperceptible and can be asymptomatic for 20 or
more years. It is of great importance to diagnose early inflammatory changes that
can lead to COPD in young asymptomatic cigarette smokers. The aim of our study
was to analyze the cell spectrum of induced sputum (IS) of young cigarette
smokers, with emphasis on T-regulatory cells. MATERIALS AND METHODS: A total of
20 healthy nonallergic smokers, 20 nonsmokers and 20 COPD patients were enrolled
in the study. After lung function measurements were taken, we performed sputum
induction and analyzed sputum cells. We evaluated the cell count of FOXP3
positive, CD4+ and CD8+ T lymphocytes by immunocytochemistry staining, and the
cell count of macrophages and neutrophils by May-Grunwald Giemsa staining.
RESULTS: Induced sputum of smokers contained a higher absolute amount of
macrophages and neutrophils when compared to nonsmokers. FOXP3-positive cells in
the sputum of young smokers showed a statistically significant increase when
compared to nonsmokers. Induced sputum of COPD patients contained an increased
absolute amount of neutrophils and FOXP3-positive Treg cells when compared to
nonsmokers. Regression analysis showed that the amount of FOXP-3 positive cells,
neutrophils and macrophages in the induced sputum was increasing with the number
of pack years. CONCLUSIONS: This study demonstrates that young smokers have early
inflammatory changes in their airways that not only initiate nonspecific
mechanisms recruiting neutrophils, but also involve specific immune mechanisms
with recruitment of T regulatory lymphocytes. The lymphocyte response is probably
adaptive.
PMID- 28705479
TI - Impact of etiology on course and outcomes of severe acute pancreatitis.
AB - BACKGROUND AND OBJECTIVE: Since the influence of etiological factors on the
course and outcomes of acute pancreatitis (AP) is not fully understood yet, the
aim of the study was to compare the outcomes of alcoholic and biliary severe
acute pancreatitis (SAP). MATERIALS AND METHODS: We investigated 81 patients with
alcoholic and biliary SAP. Demographic data, etiologic factors, severity scores,
intra-abdominal pressure, imaging studies, interventions, and treatment outcomes
were prospectively entered into specially maintained database and subsequently
analyzed. RESULTS: No statistically significant difference was observed in the
prevalence of SAP in biliary and alcoholic AP groups (P=0.429). Although, in the
biliary SAP group patients were predominantly elderly women (P=0.003), the total
in-hospital stay was longer in alcoholic SAP patients (P=0.021). The abdominal
compartment syndrome developed more frequently (P=0.041) and necrosectomy was
more frequently performed in alcoholic SAP group (not statistically significant).
Although not statistically significant, a lower mortality rate among biliary SAP
patients (25.0% vs. 13.5%) was observed. CONCLUSIONS: We defined a trend toward
decreased incidence of infected necrosis in larger volume (>=30%) pancreatic
necrosis, absence of abdominal compartment syndrome, lower rate of
necrosectomies, shorter in-hospital stay, and an insignificantly reduced
mortality rate in biliary SAP patients, indicating more favorable course of
biliary SAP.
PMID- 28705480
TI - Comparison of body composition, nutritional status, functional status, and
quality of life between osteoporotic and osteopenic postmenopausal women.
AB - BACKGROUND AND OBJECTIVE: Osteoporosis is a condition that affects body
composition, physical activity, and psychological state. We aimed to examine the
differences between osteoporotic and osteopenic postmenopausal women with respect
to body composition, nutrition, functional status, and quality of life. MATERIALS
AND METHODS: A total of 102 osteopenic (Group 1) and 100 osteoporotic (Group 2)
patients were enrolled in the study. Bone mineral density (BMD), fat tissue mass
(FTM), lean tissue mass (LTM), and bone mineral content (BMC) were evaluated
using dual-energy X-ray absorbtiometry. Nutritional status of the patients was
assessed with the Mini Nutritional Assessment (MNA), functional status with the
Nottingham Extended Activities of Daily Living (NEADL) scale, and quality of life
with the assessment of health-related quality of life in osteoporosis (ECOS-16).
RESULTS: Group 2 had significantly lower FTM, LTM, and MNA scores than Group 1
(P<0.05). NEADL and ECOS-16 scores did not differ between the groups (P>0.05). A
significant correlation was found between MNA and FTM, LTM, BMC, and BMD
(P<0.05). Whereas the assessment of functional status showed a significant
positive correlation with BMD and a significant negative correlation with age
(P<0.05), no significant correlation was found between functional status and body
composition (P>0.05). CONCLUSIONS: We found lower FTM and LTM values and a poorer
nutritional status in osteoporotic patients than in osteopenic ones. Nutritional
status was correlated with body composition and BMD, and functional status was
correlated with age and BMD.
PMID- 28705481
TI - An evaluation of the effectiveness and safety of midazolam in children undergoing
dental surgery.
AB - OBJECTIVE: The aim of this study was to evaluate the effectiveness and safety of
oral midazolam in children undergoing dental surgery. MATERIALS AND METHODS: A
prospective, randomized, controlled trial was conducted to assess the
effectiveness and safety of midazolam in children. Patients aged 2-9 years who
underwent dental surgery under general anesthesia were randomly allocated into
one of the four groups: midazolam 0.2mg/kg dose group (n=30); midazolam 0.21
0.4mg/kg dose group (n=15); midazolam more than 0.41mg/kg dose group (n=15) or
the placebo group (n=31). The effectiveness of midazolam on sedation was assessed
by the evaluation of vital signs, such as the respiratory and heart rate, oxygen
saturation and the patients' reactive behaviors, in comparison with the placebo.
RESULTS: The scores of the ratings for sleep, movement and crying, as well as
patients' reactions at the moment of separation from their parents and their
collaboration with the staff were statistically significantly better among
patients who received oral midazolam compared with the placebo. There were
statistically significant direct correlations between the doses of midazolam and
higher sleep, movement, crying and reaction scores 30min after premedication as
well as higher scores of patients upon separation from their parents. There were
only a few clinically insignificant side effects. CONCLUSIONS: Oral midazolam, at
a single dose from 0.2 to 0.6mg/kg, is effective and safe, and provides the
expected sedative effects in children required by premedication for dental
surgery.
PMID- 28705482
TI - Cardiovascular changes during the performance by nonathletes of Bosco repeated
jumps anaerobic test.
AB - OBJECTIVE: The aim of this study was to find out the characteristics of
cardiovascular changes when performing Bosco repeated jumps anaerobic test
depending on the duration of jumping in a nonathletes cohort. MATERIALS AND
METHODS: Changes in arterial blood pressure indices and changes in 12-lead ECG
indices were analyzed. The characteristics of recovery after workloads were
assessed by evaluating the time of half period of recovery of registered indices
and by the Lyapunov exponent. RESULTS: The results have shown that the ratio of
JT and RR intervals of ECG (JT/RR) can be useful for outlining to what extent a
cardiovascular function was mobilized. The mobilization of cardiovascular
function when performing a 30-s jump test changed up to 0.454+/-0.012 and when
performing a Bosco test, up to the maximal values, i.e. 0.634+/-0.004. When
performing jumps of maximal intensity, a maximal change of JT/RR occurrence was
between 50 and 60s. The increasingly serious myocardial ischemic episodes were
observed at the onset of the jumping task. The duration of 60-s of all-out jump
test has made an influence on the stability of the recovery processes of
cardiovascular indices, i.e. the nonexponential type of recovery was observed.
CONCLUSIONS: When performing Bosco 60-s repeated jumps in an anaerobic test, a
maximal mobilization of the cardiovascular system occurs between 50 and 60s. The
30-s all-out test duration in jumping is enough to outline at what extent
cardiovascular function was mobilized as well as to assess other functional
characteristics during high intensity intensive exercising.
PMID- 28705483
TI - Healthcare-associated infections in Northern Russia: Results of ten point
prevalence surveys in 2006-2010.
AB - BACKGROUND AND OBJECTIVE: Statistics on healthcare-associated infections (HAIs)
in Russia is scarce and has been considered to suffer from underreporting. We
assessed the prevalence and changes in the prevalence of HAIs over 5 years and
identified factors associated with acquiring HAIs in the pediatric hospital in
Arkhangelsk, Northern Russia. MATERIALS AND METHODS: Ten cross-sectional studies
were conducted in the Arkhangelsk regional pediatric hospital biannually during
2006-2010. We used a standardized protocol, including the criteria of HAI
proposed by the Centers for Disease Control and Prevention. Binary logistic
regression was applied to study factors associated with HAI. RESULTS: Altogether,
3264 inpatients were enrolled in the study and 347 of them had HAI (11.2%). The
prevalence of HAI per survey ranged from 7.1% (95% CI: 4.8%-10.4%) to 16.7% (95%
CI: 13.1%-21.2%). The most prevalent HAIs were upper respiratory tract infections
5.1% (95% CI: 4.4%-5.9%), followed by urinary tract infections, 1.5% (95% CI:
1.2%-2.0%), and acute gastroenteritis, 1.4% (95% CI: 1.1%-1.9%). Compared to
infants, children aged 5-9 years (OR=0.7, 95% CI: 0.4-1.0), 10-14 years (OR=0.4,
95% CI: 0.3-0.7), and >=15 years (OR=0.3, 95% CI: 0.2-0.5) were less likely to
have HAI. Neutropenia (OR=1.5, 95% CI: 1.0-2.3) and use of intravascular
catheter(s) (OR=1.8, 95% CI: 1.1-3.0) were positively associated with HAI.
CONCLUSIONS: The observed prevalence of HAIs is within the range reported in
several other European countries. We do not recommend generalizing our findings
to other Russian settings given considerable variations between regions in both
socio-economic situation and conditions of medical facilities.
PMID- 28705484
TI - Is it All About the Money? Not All Surgical Subspecialization Leads to Higher
Lifetime Revenue when Compared to General Surgery.
AB - OBJECTIVE: It is believed that spending additional years gaining expertise in
surgical subspecialization leads to higher lifetime revenue. Literature shows
that more surgeons are pursuing fellowship training and dedicated research years;
however, there are no data looking at the aggregate economic impact when training
time is accounted for. It is hypothesized that there will be a discrepancy in
lifetime income when delay to practice is considered. DESIGN: Data were collected
from the Medical Group Management Association's 2015 report of average annual
salaries. Fixed time of practice was set at 30 years, and total adjusted revenue
was calculated based on variable years spent in research and fellowship. All
total revenue outcomes were compared to general surgery and calculated in US
dollars. PARTICIPANTS: The financial data on general surgeons and 9 surgical
specialties (vascular, pediatric, plastic, breast, surgical oncology,
cardiothoracic, thoracic primary, transplant, and trauma) were examined. RESULTS:
With fellowship and no research, breast and surgical oncology made significantly
less than general surgery (-$1,561,441, -$1,704,958), with a difference in
opportunity cost equivalent to approximately 4 years of work. Pediatric and
cardiothoracic surgeons made significantly more than general surgeons, with an
increase of opportunity cost equivalent to $5,301,985 and $3,718,632,
respectively. With 1 research year, trauma surgeons ended up netting less than a
general surgeon by $325,665. With 2 research years, plastic and transplant
surgeons had total lifetime revenues approximately equivalent to that of a
general surgeon. CONCLUSIONS: Significant disparities exist in lifetime total
revenue between surgical subspecialties and in comparison, to general surgery.
Although most specialists do gross more than general surgeons, breast and
surgical oncologists end up netting significantly less over their lifetime as
well as trauma surgeons if they do 1 year of research. Thus, the economic
advantage of completing additional training is dependent on surgical field and
duration of research.
PMID- 28705485
TI - Trainees as Agents of Change in the Opioid Epidemic: Optimizing the Opioid
Prescription Practices of Surgical Residents.
AB - OBJECTIVE: Opioid abuse has become an epidemic in the United States, causing
nearly 50,000 deaths a year. Postoperative pain is an unavoidable consequence of
most surgery, and surgeons must balance the need for sufficient analgesia with
the risks of overprescribing. Prescribing narcotics is often the responsibility
of surgical residents, yet little is known about their opioid-prescribing habits,
influences, and training experience. DESIGN: Anonymous online survey that
assessed the amounts of postoperative opioid prescribed by residents, including
type of analgesia, dosage, and number of pills, for a series of common general
surgery procedures. Additional questions investigated influences on opioid
prescription, use of nonnarcotic analgesia, degree of engagement in patient
education on opioids, and degree of training received on analgesia and opioid
prescription. SETTING: Accreditation Council for Graduate Medical Education
accredited general surgery program at a university-based tertiary hospital.
PARTICIPANTS: Categorical and preliminary general surgery residents of all
postgraduate years. RESULTS: The percentage of residents prescribing opioids
postprocedure ranged from 75.5% for incision and drainage to 100% for open hernia
repair. Residents report prescribing 166.3 morphine milligram equivalents of
opioid for a laparoscopic cholecystectomy, yet believe patients will only need an
average of 113.9 morphine milligram equivalents. The most commonly reported
influences on opioid-prescribing habits include attending preference (95.2%),
concern for patient satisfaction (59.5%), and fear of potential opioid abuse
(59.5%). Only 35.8% of residents routinely perform a narcotic risk assessment
before prescribing and 6.2% instruct patients how to properly dispose of excess
opioids. More than 90% of residents have not had formal training in best
practices of pain management or opioid prescription. CONCLUSION AND RELEVANCE:
Surgical trainees are relying almost exclusively on opioids for postoperative
analgesia, often in excessive amounts. Residents are heavily influenced by their
superiors, but are not receiving formal opioid-prescribing education, pointing to
a great need for increased resident education on postoperative pain and opioid
management to help change prescribing habits.
PMID- 28705486
TI - The influence of adipose tissue location on postural control.
AB - A growing body of evidence suggests, that excessive body weight is inseparably
connected with postural instability. In none of previous studies, body weight
distribution has been considered as a factor, which may affect results of a
static posturography. The purpose of the present study is to quantify some center
of foot pressure (COP) characteristics in 40 obese women with android type of
obesity (waist-to-hip ratio - WHR>=0.85, BMI: 37.5+/-5.4) and 40 obese women with
gynoid type of obesity (WHR<0.85, BMI: 36.9+/-5.1). Variables of postural sway
were acquired while subjects were standing quietly on a force plate with eyes
open and closed. Both in the sagittal and frontal plane sway range, average
velocity, and maximal velocity of COP were calculated. Moreover, the total
average velocity and total maximal velocity of the COP displacement were
computed. Women with abdominal obesity showed a larger sway range in the anterior
posterior plane with eyes open (p<0.0282) and eyes closed conditions (p<0.0115)
and a greater maximal COP velocity to compare with subjects with gynoidal obese
type (p<0.0112) with eyes closed condition. The postural stability in obese women
from the biomechanical point of view is strongly dependent on body distribution.
Women with the abdominal obesity type may be exposed to a greater risk of
postural instability as compare to women with gynoid fat distribution.
PMID- 28705487
TI - Amputee locomotion: Frequency content of prosthetic vs. intact limb vertical
ground reaction forces during running and the effects of filter cut-off
frequency.
AB - Compared to intact limbs, running-specific prostheses have high resonance non
biologic materials and lack active tissues to damp high frequencies. These
differences may lead to ground reaction forces (GRFs) with high frequency
content. If so, ubiquitously applying low-pass filters to prosthetic and intact
limb GRFs may attenuate veridical high frequency content and mask important and
ecologically valid data from prostheses. To explore differences in frequency
content between prosthetic and intact limbs we divided signal power from
transtibial unilateral amputees and controls running at 2.5, 3.0, and 3.5m/s into
Low (<10Hz), High (10-25Hz), and Non-biologic (>25Hz) frequency bandwidths.
Faster speeds tended to reduce the proportion of signal power in the Low
bandwidth while increasing it in the High and Non-biologic bandwidths. Further,
prostheses had lower proportions of signal power at the High frequency bandwidth
but greater proportions at the Non-biologic bandwidth. To evaluate whether these
differences in frequency content interact with filter cut-offs and alter results,
we filtered GRFs with cut-offs from 1 to 100Hz and calculated vertical impact
peak (VIP). Changing cut-off had inconsistent effects on VIP across speeds and
limbs: Faster speeds had significantly larger changes in VIP per change in cut
off while, compared to controls, prosthetic limbs had significantly smaller
changes in VIP per change in cut-off. These findings reveal differences in GRF
frequency content between prosthetic and intact limbs and suggest that a cut-off
frequency that is appropriate for one limb or speed may be inappropriate for
another.
PMID- 28705488
TI - Prevalence of Trypanosoma cruzi infection in dogs and small mammals in Nuevo
Leon, Mexico.
AB - Chagas disease, caused by the protozoan Trypanosoma cruzi, is an important public
health concern in areas extending from South America northward into the southern
United States of America. Although this hemoflagellate has many wild and domestic
mammalians reported as reservoir hosts, studies on this subject are scarce in
Nuevo Leon state, a region located in northeastern Mexico. This cross-sectional
study showed that the general prevalence of T. cruzi infection in Nuevo Leon
state was 14.5% (35/241), this percentage matching the ones determined by PCR and
traditional diagnostics. Localities and infected mammals did not significantly
differ (chi2=6.098, p=0.192); however the number of infected animals was highly
correlated with mammalian species (p=0.009). Striped skunks (Mephitis mephitis)
were found to be the most infected overall (11/34, 32.3%), while dogs (Canis
familiaris) had the lowest prevalence. In conclusion, although the prevalence of
T. cruzi infection in small mammals was lower in Nuevo Leon than in other states
of Mexico, our results provide new locality records, including striped skunks,
opossums (Didelphis marsupialis) and dogs, and extend the recorded area to
woodrats (Neotoma micropus).
PMID- 28705489
TI - The effects of estradiol valerate and remifemin on liver lipid metabolism.
AB - To investigate the lipid metabolism dysregulation in the liver of ovariectomized
(OVX) rats and effects of estradiol valerate (E) and remifemin (ICR) thereon,
forty female Sprague-Dawley rats were randomly divided into sham-operated (SHAM),
OVX, OVX+E, and OVX+ICR group. After 4 weeks' E or ICR treatment, serum estrogen,
cholesterol, and triglyceride levels; lipid droplets in hepatocytes; hepatocyte
morphology; and the expression of estrogen receptor alpha (ERalpha), liver X
receptor (LXR), and sterol regulatory element binding proteins (SREBPs) in the
liver of the rats were assessed. OVX rats had significantly decreased serum
estrogen levels, which significantly increased after treatment with E but not
with ICR. Serum triglyceride levels and the amount of lipid droplets in
hepatocytes increased after ovariectomy, and significantly decreased after E
treatment. In addition, ICR treatment markedly increased serum triglyceride
levels and lipid droplet size. No significant differences in the serum
cholesterol levels were observed among the four groups. After ovariectomy,
hepatocyte mitochondria became hypertrophic and misformed, which were reversed
with E or ICR treatment. ICR-treated rats also showed endoplasmic reticulum
disorganization. After ovariectomy, ERalpha and LXR levels significantly
decreased while SREBP expression increased. E treatment increased ERalpha and LXR
levels while ICR treatment only increased LXR expression. E treatment decreased
SREBP-1c levels, whereas SREBP-1c levels increased with ICR treatment. Treatment
with E significantly reversed the ovariectomy-induced dysregulation of hepatocyte
lipid metabolism, which was, however, exacerbated with ICR treatment. The effects
of E and ICR on hepatocyte lipid metabolism may involve the regulation of LXR and
SREBP-1c.
PMID- 28705490
TI - Deformation correction for image guided liver surgery: An intraoperative fidelity
assessment.
AB - BACKGROUND: Although systems of 3-dimensional image-guided surgery are a valuable
adjunct across numerous procedures, differences in organ shape between that
reflected in the preoperative image data and the intraoperative state can
compromise the fidelity of such guidance based on the image. In this work, we
assessed in real time a novel, 3-dimensional image-guided operation platform that
incorporates soft tissue deformation. METHODS: A series of 125 alignment
evaluations were performed across 20 patients. During the operation, the surgeon
assessed the liver by swabbing an optically tracked stylus over the liver surface
and viewing the image-guided operation display. Each patient had approximately 6
intraoperative comparative evaluations. For each assessment, 1 of only 2 types of
alignments were considered: conventional rigid and novel deformable. The series
of alignment types used was randomized and blinded to the surgeon. The surgeon
provided a rating, R, from -3 to +3 for each display compared with the previous
display, whereby a negative rating indicated degradation in fidelity and a
positive rating an improvement. RESULTS: A statistical analysis of the series of
rating data by the clinician indicated that the surgeons were able to perceive an
improvement (defined as a R > 1) of the model-based registration over the rigid
registration (P = .01) as well as a degradation (defined as R < -1) when the
rigid registration was compared with the novel deformable guidance information (P
= .03). CONCLUSION: This study provides evidence of the benefit of deformation
correction in providing an accurate location for the liver for use in image
guided surgery systems.
PMID- 28705491
TI - Proposal of selection criteria for operative resection of hepatocellular
carcinoma with inferior vena cava tumor thrombus incorporating hepatic arterial
infusion chemotherapy.
AB - BACKGROUND: Because operative resection of hepatocellular carcinoma with inferior
vena cava tumor thrombus has been associated with a substantial risk of
recurrence and postoperative morbidity, adequate patient selection for resection
is necessary. Our aim was to propose selection criteria for resection of
hepatocellular carcinoma with inferior vena cava tumor thrombus. METHODS: Long
term outcomes were analyzed retrospectively in 39 operative cases of
hepatocellular carcinoma with inferior vena cava tumor thrombus (1996-2015).
Since 2003, preoperative hepatic arterial infusion chemotherapy instead of
immediate resection has been performed in patients with advanced inferior vena
cava tumor thrombus, defined as those patients with suspected extrahepatic
metastasis, who will need extracorporeal circulation, or who have marginal liver
function and/or multiple bilobar tumors. Indication for resection has been based
on the tumor response to hepatic arterial infusion chemotherapy thereafter.
RESULTS: The median survival time for all patients was 15.2 months. Multivariate
analysis revealed that preoperative hepatic arterial infusion chemotherapy
(hazard ratio: 0.30), use of extracorporeal circulation (3.12), and extrahepatic
metastasis (2.67) were independent prognostic factors for overall survival. Among
patients with initially advanced inferior vena cava tumor thrombus, preoperative
hepatic arterial infusion chemotherapy was associated with a much more favorable
prognosis compared with no hepatic arterial infusion chemotherapy (median
survival time: unreached vs 8.3 months, P = .007). Overall survival was
significantly worse in patients with uncontrolled, advanced inferior vena cava
tumor thrombus than in those without advanced inferior vena cava tumor thrombus
or with advanced inferior vena cava tumor thrombus controlled by preoperative
hepatic arterial infusion chemotherapy (median survival time: 10.4 vs 26.1
months, P = .039). CONCLUSION: An effective response to hepatic arterial infusion
chemotherapy and subsequent operative resection salvaged patients with initially
advanced inferior vena cava tumor thrombus. Our results suggest that operative
resection should be indicated only in patients without advanced inferior vena
cava tumor thrombus or with advanced inferior vena cava tumor thrombus controlled
by preoperative hepatic arterial infusion chemotherapy.
PMID- 28705492
TI - Primary lymph node gastrinoma: A single institution experience.
AB - BACKGROUND: Gastrinomas are rare neuroendocrine tumors that ectopically secrete
gastrin and classically originate within the duodenum or pancreas. The presence
of primary lymph node gastrinoma is controversial. We report on a single
institution's experience with gastrinoma, with focus on primary lymph node
tumors. METHODS: Patients who underwent operative resection of gastrinoma between
1992 and 2016 at a single institution were identified. A diagnosis of primary
lymph node gastrinoma was defined as tumor confined to one or more resected
peripancreatic lymph nodes, negative localization for any extra-nodal disease and
normal gastrin postresection. RESULTS: In the study, 39 consecutive patients
underwent operative resection of gastrinoma. Mean age was 53 years and 49% were
male. 93% of patients had successful preoperative localization. Furthermore, 19
patients (49%) underwent enucleation of their tumor and 14 (35.9%) a pancreatic
resection. Overall 5- and 10-year survival for all patients was 80.8% and 60.7%,
respectively. Primary lymph node gastrinoma was identified in 11 cases (28.2%).
The presentation of primary lymph node and non-primary lymph node patients were
similar. There was no significant difference in operation type, tumor size, or
overall survival. At median follow-up of 59 months, patients with primary lymph
node gastrinoma were less likely to have persistent or recurrent disease (9.1% vs
42.9%, P = .04). CONCLUSION: This series supports the existence of primary lymph
node gastrinomas, and indicates that as many as 1 in 4 patients with gastrinoma
have this form of the disease. This entity should be considered when an isolated
pathologic lymph node is identified, although thorough exploration is still
recommended to exclude other occult disease.
PMID- 28705493
TI - Tracheopleural and esophagopleural fistula complicating corrosive-induced
esophageal cancer.
PMID- 28705494
TI - Inflammation initiated by stressed organelles.
AB - Key cellular functions including those related to energy metabolism, organization
of the genetic information or production of membrane-bound and secreted proteins
are compartmentalized within organelles. Various stresses such as differentiation
programs, viral and bacterial infections, perturbations in protein production,
mechanical constraints, changes in the environment and nutriment accessibility
can impact cellular homeostasis and organelle integrity. Perturbations of these
cellular compartments trigger repair and adaptation programs aimed at restoring
homeostasis. These events are often associated with low-grade inflammation also
termed parainflammation. While the nature and mechanisms of danger signals
released by irremediably damaged cells are well understood, how transiently
stressed cells trigger inflammation is still poorly understood. Emerging studies
highlighted new mechanisms by which stress pathways promote inflammation.
Cytosolic innate immune pathways are engaged by signals stemming from perturbed
organelles such as the mitochondria, the endoplasmic reticulum (ER) or the
nuclear envelope (NE). These observations indicate that these pathways function
as guardians of cellular homeostasis and may contribute to disease in pathologies
characterized by perturbations of cellular homoeostasis. Mitochondria-stress, ER
stress or NE-stress are emerging as proinflammatory signals that contribute to
human conditions and diseases.
PMID- 28705495
TI - Glial-associated changes in the cerebral cortex after collagenase-induced
intracerebral hemorrhage in the rat striatum.
AB - Striatum and the cerebral cortex are regions susceptible to secondary injury
after intracerebral hemorrhage (ICH) and glial cells in tissue adjacent to the
hematoma may modulate cellular vulnerability after brain damage. Nonetheless,
while the glial- associated changes occurring in the cerebral cortex after ICH
may be important in maximizing brain recovery, they are not fully understood. The
aim of this study was to evaluate the temporal profile of glial-associated
changes in the cerebral cortex after ICH. First, the motor consequences of ICH
and its relation to the lesion volume were analyzed. Secondly, glial cell
proportion (GFAP+ and S100B+ astrocytes, CD11+ microglia) in the ipsilesional
sensorimotor cortex and striatum, using flow cytometry were evaluated. ELISA was
used to measure GFAP and S100B content in these structures as well as S100B
levels in serum and cerebral spinal fluid. Main results revealed that ICH induced
a delayed increase in GFAP+ cells in the sensorimotor cortex, as compared to the
striatum, although the pattern of GFAP expression was similar in both structures.
Interestingly, the time-curve patterns of both S100B and CD11+ microglial cells
differed between the cortex and striatum. Altogether, these results suggest a
different dynamics of glial-associated changes in the cerebral cortex, suggesting
it is a vulnerable structure and undergoes an independent secondary process of
reactive glial plasticity following intracerebral hemorrhage.
PMID- 28705496
TI - The effect of CXCR2 inhibition on seizure activity in the pilocarpine epilepsy
mouse model.
AB - C-X-C motif chemokine receptor 2 (CXCR2) is one of the most well characterized
chemokine receptors and is a potential target for treating brain pathologies
involving inflammatory processes, including epilepsy. However, the role of CXCR2
in epilepsy has not been investigated, and whether CXCR2 modulates seizure
activity in temporal lobe epilepsy (TLE) remains unknown. In this study, we aimed
to determine the potential role of CXCR2 in intractable TLE patients and in
pilocarpine-induced epileptic mice. Here, through Western blotting and semi
quantitative immunohistochemistry, we detected that CXCR2 protein expression was
up-regulated (by nearly 50%) in the temporal neocortex of TLE patients and in the
hippocampus and adjacent temporal cortex of pilocarpine mice model. Double-label
immunofluorescence and immunohistochemical analysis indicated that CXCR2 was
expressed in neurons. To investigate the effect of the CXCR2 selective antagonist
SB225002 on seizure activity, SB225002 was i.p. administered during the latency
window of spontaneous recurrent seizures (SRSs). This treatment increased (by
nearly 40%) the latency of SRSs and reduced (by nearly 50%) the frequency of SRSs
during the chronic period of epilepsy. This study suggests that CXCR2 plays a
critical role in modifying epileptic seizure activity and that CXCR2 blockade
could be a potential molecular therapeutic target for epilepsy.
PMID- 28705497
TI - Quicksilver: Fast predictive image registration - A deep learning approach.
AB - This paper introduces Quicksilver, a fast deformable image registration method.
Quicksilver registration for image-pairs works by patch-wise prediction of a
deformation model based directly on image appearance. A deep encoder-decoder
network is used as the prediction model. While the prediction strategy is
general, we focus on predictions for the Large Deformation Diffeomorphic Metric
Mapping (LDDMM) model. Specifically, we predict the momentum-parameterization of
LDDMM, which facilitates a patch-wise prediction strategy while maintaining the
theoretical properties of LDDMM, such as guaranteed diffeomorphic mappings for
sufficiently strong regularization. We also provide a probabilistic version of
our prediction network which can be sampled during the testing time to calculate
uncertainties in the predicted deformations. Finally, we introduce a new
correction network which greatly increases the prediction accuracy of an already
existing prediction network. We show experimental results for uni-modal atlas-to
image as well as uni-/multi-modal image-to-image registrations. These experiments
demonstrate that our method accurately predicts registrations obtained by
numerical optimization, is very fast, achieves state-of-the-art registration
results on four standard validation datasets, and can jointly learn an image
similarity measure. Quicksilver is freely available as an open-source software.
PMID- 28705498
TI - [Hepatonephritis during the treatment of malaria by the therapeutic combinations
from a pharmacovigilance database].
AB - INTRODUCTION: Prior studies have shown an association between the onset of
hepatonephritis and the use of arteminisin-based combination therapy (ACT) during
the treatment of uncomplicated malaria. The objective of this study was to
identify the risk factors of hepatonephritis occurrence because of the
uncertainty regarding the appearance and the aggravation of this syndrome.
METHODS: A case-non case study was carried out on 428 notifications of
pharmacovigilance extracted from the database of the clinical pharmacology
department of the teaching hospital of Cocody from 2008 to 2012. Twenty-two cases
of hepatonephritis were identified. Univariate analysis and multivariate logistic
regression were performed to identify the risk factors and an adjusted odds ratio
(AOR) was calculated for each factor. The cut-off for significant association was
set at 0.05. RESULTS: The average age of cases was comparable with that of non
cases (34.04+/-3.68 years versus 33.94+/-3.92 years) with a median duration of
therapy of 5 days and 6 days respectively. Male (AOR: 6.71; P<0.0001), toxic
antecedents, traditherapy (AOR: 6.25; P<0.0001), consumption of CTA (AOR: 1.25;
P<0.0001), betalactam (AOR: 0.46; P<0.0001), fluoroquinolone and self-medication
(AOR: 2.89; P<0.0001) would be the majors risk factors associated with
hepatonephritis onset. The risk increased with the number of antimalarial drugs
taken. The evolution towards the offset was less frequent (AOR: 0.078; P<0.02).
CONCLUSION: The risk factors of hepatonephritis were the consumption of malarial
drugs and connected molecules, self-medication and misuse. The outcome was
generally unfavourable. Both the general population and health professionals
should be trained on the good use of the antimalarial drugs.
PMID- 28705499
TI - Development of silver nanoparticles loaded chitosan-alginate constructs with
biomedical potentialities.
AB - Herein, a facile biosynthesis of silver nanoparticles (AgNPs) and AgNPs-loaded
chitosan-alginate constructs with biomedical potentialities is reported. The UV
vis spectroscopic profile confirmed the synthesis of AgNPs using methanolic
leaves extract of Euphorbia helioscopia. The newly developed AgNPs were
characterized using various analytical and imaging techniques including UV-vis
and FT-IR spectroscopy, X-ray diffraction (XRD), scanning electron microscopy
(SEM), energy dispersive spectroscopy (EDS), atomic force microscopy (AFM), and
transmission electron microscopy (TEM). The optimally yielded AgNPs at 24h
reaction period were loaded onto various chitosan-alginate constructs. A maximum
of 95% loading efficiency (LE) was recorded with a chitosan: alginate ratio at
2:1, followed by 81% at 2:2 ratios. The anti-bacterial activities of AgNPs and
AgNPs loaded chitosan-alginate constructs were tested against six bacterial
strains i.e. Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella
pneumoniae, Acinetobacter baumannii, Morganella morganii and Haemophilus
influenza. A significant reduction in the log values was recorded for all test
constructs, in comparison to the initial bacterial count (control value, i.e.,
1.5*108 CFU/mL). The cytotoxicity profile revealed complete biocompatibility
against normal cell line i.e. L929. Almost all constructs showed considerable
cytotoxicity up to certain extant against human epithelial cells (HeLa) cancer
cells. In summary, the highest antibacterial activities along with anti-cancer
behavior both suggest the biomedical potentialities of newly engineered AgNPs and
AgNPs-loaded chitosan-alginate constructs.
PMID- 28705500
TI - Development and characterization of bioactive edible films from spider crab (Maja
crispata) chitosan incorporated with Spirulina extract.
AB - Active food packaging films based on crab chitosan and Spirulina extract (SE)
were developed. The effects of the SE incorporation at different levels on
physical (color, opacity water vapor and oxygen permeability) and mechanical
(tensile strength and elongation at break) properties of chitosan films were
investigated. FTIR was carried out to observe the potential modifications of the
chitosan films when incorporated with SE. The obtained results suggested that
incorporation of SE into chitosan films improved mechanical and barrier
properties. The antioxidant activity of the chitosan/SE films was characterized
by means of three different analytical assays (DPPH, FRAP and FIC). Crab chitosan
edible films containing SE showed higher antioxidant activity, regardless
concentrations and methods assayed. Furthermore, the antioxidant activity
occurred in a concentration-dependent manner. The agar disc diffusion method was
used to determine the antibacterial activities of chitosan edible films against
Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Listeria
monocytogenes, Salmonella typhimurium, Bacillus subtilis and Bacillus cereus. The
chitosan/SE films were more effective (p<0.05) against five of the seven tested
bacteria. The obtained crab chitosan edible films incorporated with SE showed
great potential to be used for active food packaging due to its excellent
antioxidant and antibacterial activities.
PMID- 28705501
TI - Morphology, crystallinity, pasting, thermal and quality characteristics of
starches from adzuki bean (Vigna angularis L.) and edible kudzu (Pueraria
thomsonii Benth).
AB - Starches were isolated from adzuki bean (Vigna angularis L.) and edible kudzu
(Pueraria thomsonii Benth) and investigated for their physico-chemical,
morphological, pasting, crystallinity, thermal and FT-IR spectroscopic
characteristics. Statistical analysis of physico-chemical and functional
characteristics showed significant (p<0.05) difference between isolated starches
from adzuki bean and edible kudzu. The XRD pattern of starches from adzuki bean
and edible kudzu showed A-type with reflections (2theta) at 15.0 degrees , 17.03
degrees , 17.89 degrees , 23.18 degrees and 15.12 degrees , 17.03 degrees , 17.77
degrees , 23.3 degrees , respectively. The starch granules from adzuki bean were
smooth, round, oval to kidney or irregular while those of edible kudzu starch
were spherical, hemispherical and polygonal. Edible kudzu starch exhibited high
pasting temperature, gelatinization temperatures, enthalpy and less pasting
parameters as compared to starch from adzuki bean. Peaks in FT-IR spectra of both
starches shown its carbohydrate nature. Starch from adzuki bean showed high
swelling power and solubility as compared to edible kudzu, and enhanced the
swelling power and solubility of isolated starches with the temperature raised
from 50 degrees C and 90 degrees C. Finally, this work offers data for the
application of starches isolated from adzuki bean and edible kudzu that would be
applicable for both food and non-food industries.
PMID- 28705502
TI - Synthesis and characterization of hydrogel films of carboxymethyl tamarind gum
using citric acid.
AB - The objective of this study was to synthesize and characterize citric acid
crosslinked carboxymethyl tamarind gum (CMTG) hydrogels films. The hydrogel films
were characterized by Attenuated total reflectance-Fourier transform infrared
(ATR-FTIR) spectroscopy, solid state 13C-nuclear magnetic resonance (13C NMR)
spectroscopy and differential scanning calorimeter (DSC). The prepared hydrogel
films were evaluated for the carboxyl content and swelling ratio. The model drug
moxifloxacin hydrochloride was loaded into hydrogels films and drug release was
studied at pH 7.4. The hemolysis assay was used to study the biocompatibility of
hydrogel films. The results of ATR-FTIR, solid state 13C NMR and DSC confirmed
the formation of ester crosslinks between citric acid and CMTG. The total
carboxyl content of hydrogel film was found to be decreased when amount of CMTG
was increased. The swelling of hydrogel film was found to be decreased with
increase in curing temperature and time. CMTG hydrogel films showed high drug
loading with non-Fickian release mechanism suggesting controlled release of drug.
The hydrogel films were found to be biocompatible. It can be concluded that the
citric acid can be used for the preparation of CMTG hydrogel films. Further, CMTG
hydrogel film can be used potentially for controlled release of drug.
PMID- 28705503
TI - Building a bio-based hydrogel via electrostatic and host-guest interactions for
realizing dual-controlled release mechanism.
AB - Bio-based hydrogel containing cyclodextrins (CDs) is of a promising polymer
material that could display many advantages including wide availability,
sustainability, biocompatibility and biodegradability, especially the inherent
encapsulation ability with hydrophobic substance. To obtain these, the
electrostatic and host-guest interactions were introduced and a hydrogel with
three-dimensional double network structures was built. For preparing a spherical
biopolymer cage, hydroxyethyl cellulose (HEC) and modified chitosan (HACC) were
cross-linked by a one-pot reaction. The existence of HACC in this hydrogel
provides a positive charge core to attract negative host molecule of
sulfobutylether-beta-cyclodextrin (SEB-beta-CD). The loading amount of SEB-beta
CD were determined by the method of weight increment and photometric titration,
respectively, and an average content of active SEB-beta-CD in our prepared
hydrogel is more than 50%, much higher than the grafting of CD on biopolymers
materials through chemical reaction. By the host-guest interaction, hydrophobic
molecule of PP could adsorb rapidly in our prepared hydrogel and sustain-release
in aqueous solution. Through ion-exchange interaction, different negative ions
were studied for obtaining a control release of SEB-beta-CD, which is to achieve
the purpose of rapid release of hydrophobic guest molecule.
PMID- 28705504
TI - Determination of optimum experimental conditions for preparation and functional
properties of hydroxypropylated, phosphorylated and hydroxypropyl-phosphorylated
glutinous rice starch.
AB - Optimization of the preparation of hydroxypropylated, phosphorylated and
hydroxypropyl-phosphorylated glutinous rice starch was performed using a response
surface methodology comprising three variables at three levels. Multi-linear
regression was used to fit the degree of substitution and molar substitution
against. Optimal reaction conditions were 9h, 42 degrees C, 10%
(hydroxypropylated), 148min, 150 degrees C, 7% (phosphorylated) and 95min, 140
degrees C, 7.8% (hydroxypropyl-phosphorylated). For hydroxypropylated, predicted
optimal and experimental molar substitution values were found to be identical:
0.20. Both the phosphorylated and hydroxypropyl-phosphorylated, the predicted
optimal and experimental degree of substitution values was 0.02. Static
rheological analysis revealed a pseudoplastic nature for native and modified
starches and an increase in apparent viscosity following modification. Dynamic
rheological analysis indicated an entanglement network system for native
glutinous rice starch suspension, but weak elastic gel-like structure for
modified starches as the storage modulus (G') exceeded the loss modulus (G").
Additionally, chemical modification improved the freeze-thaw stability, swelling
power, solubility and paste clarity.
PMID- 28705505
TI - Physicochemical properties, in-vitro digestibility and structural elucidation of
RS4 from rice starch.
AB - Starches extracted from four different rice cultivars were phosphorylated by
using STMP/STPP to make modified food starches with high contents of type 4
resistant starch (RS4). The results revealed 10- fold improvement in RS4 content
by the phosphorylation of starch. The phosphorus % and DS values of rice starches
ranged from 0.33 to 0.35, and 0.016 to 0.018, respectively. FT-IR spectroscopy
showed reduction of OH stretching band at 3290cm-1 and the appearance of PO at
1244-1266cm-1 which confirms crosslinking of starch with STMP/STPP.
Phosphorylation was found to increase water absorption capacity, oil absorption
capacity, bile-acid binding and lightness, whereas amylose content, swelling
power, solubility index and light transmittance were decreased with
phosphorylation. DSC analyses revealed increase in thermal transition
temperatures of the crosslinked starches which suggests that the application of
STMP/STPP as a crosslinker can improve the integrality and stability of starch.
SEM micro-graphs revealed that phosphorylated rice starch granules retained their
integrity, while some fissures appeared on the surface of some granules. XRD
analysis revealed decreased crystallinity of RS4 rice starches.
PMID- 28705506
TI - Fabrication of novel chitosan/PAN/magnetic ZSM-5 zeolite coated sponges for
absorption of oil from water surfaces.
AB - In the present study, the chitosan (bottom layer)/polyacrylonitrile (top layer,
PAN) nanofibers were coated on the sponge surface. The synthesized magnetic Fe3O4
ZSM-5 nanozeolites have been loaded into the chitosan/PAN nanofibers to increase
the performance of nanofibers toward absorption of lubricating oil, motor oil and
pump oil from water surfaces. Scanning electron microscope (SEM), Transmission
electron microscope (TEM) and X-ray diffraction (XRD) analysis were used to
characterize the synthesized nanozeolites. The morphology and wettability of
nanofibers were determined using SEM and water contact angle tests. The influence
of Fe3O4- ZSM-5 nanozeolite content and chitosan/PAN/Fe3O4- ZSM-5 nanofiber
thickness was evaluated on the potential of sponges for oils absorption. The
maximum capacity of the chitosan/PAN/Fe3O4- ZSM-5 nanofibers coated sponges for
absorption of motor oil, lubricating oil and pump oil was found to be 99.4, 95.3
and 88.1g/g, in Fe3O4- ZSM-5 2wt.% and nanofiber thickness of 12MUm (chitosan
layer of 2MUm and PAN layer of 10MUm). The reusability of nanofibrous sponges
showed that the hydrophobic chitosan/PAN/Fe3O4- ZSM-5 nanofibers coated sponges
can be easily reused in water-oil separation for many cycles.
PMID- 28705507
TI - Dosimetric comparison of RapidPlan and manually optimized plans in volumetric
modulated arc therapy for prostate cancer.
AB - PURPOSE: This study evaluated whether RapidPlan based plans (RP plans) created by
a single optimization, are usable in volumetric modulated arc therapy (VMAT) for
patients with prostate cancer. METHODS: We used 51 previously administered VMAT
plans to train a RP model. Thirty RP plans were created by a single optimization
without planner intervention during optimization. Differences between RP plans
and clinical manual optimization (CMO) plans created by an experienced planner
for the same patients were analyzed (Wilcoxon tests) in terms of homogeneity
index (HI), conformation number (CN), D95%, and D2% to planning target volume
(PTV), mean dose, V50Gy, V70Gy, V75Gy, and V78Gy to rectum and bladder, monitor
unit (MU), and multi-leaf collimator (MLC) sequence complexity. RESULTS: RP and
CMO values for PTV D95%, PTV D2%, HI, and CN were significantly similar (p<0.05
for all). RP mean dose, V50Gy, and V70Gy to rectum were superior or comparable to
CMO values; RP V75Gy and V78Gy were higher than in CMO plans (p<0.05). RP bladder
dose-volume parameter values (except V78Gy) were lower than in CMO plans
(p<0.05). MU values were RP: 730+/-55MU and CMO: 580+/-37MU (p<0.05); and MLC
sequence complexity scores were RP: 0.25+/-0.02 and CMO: 0.35+/-0.03 (p<0.05).
CONCLUSIONS: RP plans created by a single optimization were clinically acceptable
in VMAT for patient with prostate cancer. Our simple model could reduce
optimization time, independently of planner's skill and knowledge.
PMID- 28705508
TI - Fingerprint analysis of Gelsemium elegans by HPLC followed by the targeted
identification of chemical constituents using HPLC coupled with quadrupole-time
of-flight mass spectrometry.
AB - Gelsemium elegans, which is a genus of the family Loganiaease, is commonly used
as a traditional medicine for promoting animal growth and treating rheumatoid
arthritis pain and neuropathic pain, among others. In this study, we first
established a valid high-performance liquid chromatography (HPLC) method for the
fingerprint analysis of Gelsemium elegans samples. Then, the comprehensive
detection of chemical constituents from the samples was performed using HPLC
coupled with quadrupole-time-of-flight mass spectrometry. The similarity
evaluation results showed that location and area differences influenced the
quality of the samples. An efficient strategy for the rapid targeted
identification of chemical components was matching with a developed Gelsemium
database. As a result, the accurate elemental compositions and known structures
of compounds are found as hits. This process facilitated the structural
identification of compounds combined with the accurate mass measurement of
product ions and fragmentation behaviors. Consequently, 41 components including
six alkaloids and non-alkaloids were systematically identified from Gelsemium
elegans. The results showed that at least seven relatively major components
existing in Gelsemium elegans may be useful for its quality control. The present
analytical method combined with the developed Gelsemium database was shown to be
a useful tool for investigating the chemical components of Gelsemium products.
PMID- 28705509
TI - Cytochalasin E in the lichen Pleurosticta acetabulum. Anti-proliferative activity
against human HT-29 colorectal cancer cells and quantitative variability.
AB - A biological screening of sixteen lichen extracts on human HT-29 colorectal
cancer cells, led to the selection of Pleurosticta acetabulum, a lichen widely
present in tree barks in Europe. Bioguided purification of the acetonic extract
resulted in the isolation of cytochalasin E, a common fungal metabolite. This
compound is responsible for the anti-proliferative activity of the extract. Its
presence in lichens is reported here for the first time. LC-MS quantitation of
cytochalasin E in different samples of P. acetabulum demonstrated quantitative
variations of cytochalasin E production in the lichen and especially high
concentrations in apothecia.
PMID- 28705510
TI - The chemical composition of the pharmacologically active Thymus species, its
antibacterial activity against Streptococcus mutans and the antiadherent effects
of T. vulgaris on the bacterial colonization of the in situ pellicle.
AB - The pharmacological active genus Thymus L. comprises over 200 species. Besides
its traditional pharmacological use, thyme may reduce the risk of caries disease,
however, there is very little respective literature. The pharmacological effects
can be attributed to the secondary plant metabolites. The composition of the
essential oil and the polyphenols is important for the evaluation of the
pharmacological activity. Nevertheless, there are no studies regarding a
comparative analysis of the different pharmacological thyme species. In the
present study, four different pharmacology Thymus species were cultivated under
comparable conditions, and the volatile compounds as well as the polyphenols were
characterized. In addition, the in vitro antibacterial activity against S.
mutans, one of the primary cariogenic bacterial species, as well as of the
essential oil and of the polyphenols were investigated. Furthermore, the
bacterial viability and its effect on the initial bacterial adhesion under oral
conditions were evaluated in situ for the essential oil and the polyphenols. By
GC-MS, 69 volatile compounds, and by LC-DAD-MS/MS, 46 polyphenols could be
identified. The comprehensive examination of the essential oils and the
polyphenols revealed that the main compounds were equal. However, the yield of
the essential oil and the polyphenol content differed clearly. The essential oils
of the four investigated Thymus species exhibited an antibacterial activity
against S. mutans in vitro, in contrast to the polyphenols of T. vulgaris.
Rinsing with polyphenol-rich infusions reduced the initial bacterial colonization
while the essential oil inhibited the bacterial growth on dental enamel in situ.
PMID- 28705511
TI - Hidden bifid spine at preanaesthetic consultation.
PMID- 28705512
TI - Multi-objective optimization of nitinol stent design.
AB - Nitinol stents continuously experience loadings due to pulsatile pressure, thus a
given stent design should possess an adequate fatigue strength and, at the same
time, it should guarantee a sufficient vessel scaffolding. The present study
proposes an optimization framework aiming at increasing the fatigue life reducing
the maximum strut strain along the structure through a local modification of the
strut profile.The adopted computational framework relies on nonlinear structural
finite element analysis combined with a Multi Objective Genetic Algorithm, based
on Kriging response surfaces. In particular, such an approach is used to
investigate the design optimization of planar stent cell.The results of the strut
profile optimization confirm the key role of a tapered strut design to enhance
the stent fatigue strength, suggesting that it is possible to achieve a marked
improvement of both the fatigue safety factor and the scaffolding capability
simultaneously. The present study underlines the value of advanced engineering
tools to optimize the design of medical devices.
PMID- 28705513
TI - Pediatric all-terrain vehicle (ATV) injuries: An epidemic of cost and grief.
AB - OBJECTIVE: Evaluate cost of care of all-terrain vehicle (ATV) related injuries
sustained by riders 16 years and younger in Pennsylvania. METHODS: Population
based retrospective cohort design reviewing costs of care of 78 patients (<=16
years), admitted (01/01/2007-12/31/2009) to our institution for injuries
sustained during an ATV accident. RESULTS: Cost of care varied from $322 to
$310,435. Mean and median costs for all patients were $25,760 and $8,066,
respectively. Average costs increased with increasing age. Patients wearing
helmets or driving the ATV had lower mean costs, but these trends were not
statistically significant. Crashes with stationary objects not involving rollover
or ejection had significantly lower mean costs than other crash types (p = 0.01).
Patients involved in rollover accidents were significantly more likely to require
an overnight hospital stay (OR = 3.45, p = 0.02). Patients wearing helmets were
marginally less likely to require an overnight admission (OR = 0.34, p = 0.07).
CONCLUSION: ATV crashes involving unhelmeted riders and rollover accidents result
in significant medical costs. Interventions to increase helmet use and measures
to improve stability are likely to reduce these costs and shorten hospital stays.
LEVEL OF EVIDENCE: Level IV, Economic study.
PMID- 28705514
TI - Bacillus Calmette-Guerin (BCG) vaccination patterns in the province of Quebec,
Canada, 1956-1974.
AB - BACKGROUND: In the province of Quebec, Canada, the Bacillus Calmette-Guerin (BCG)
vaccine was offered to newborns and school-age children from the 1950s to mid
1970s in an organized tuberculosis prevention program. OBJECTIVE: We aimed to
describe the annual rates of skin test administration, proportion of skin tests
that were positive, and rates of BCG vaccination from 1956 to 1974 according to
age, sex, and administrative region. METHODS: For rates, numerators were
extracted from the Quebec BCG Vaccination Registry whereas population
denominators were obtained from the Canadian Census and governmental
publications. Time trends were assessed with linear regression. RESULTS: A total
of 2,755,336 skin tests and 2,531,366 BCG vaccinations were administered. Yearly
rates of skin tests, routinely administered before vaccination among all except
newborns, were highest among children aged 5-9 (9.3 per 100) and 10-14years (7.9
per 100). The proportion of positive skin tests varied greatly by age, ranging
from 10.2% among children <1year to 67.2% among adults >=20years. The vast
majority of individuals who had a negative skin test were subsequently
vaccinated, whereas those with a positive result were not, as per recommended
guidelines. The average annual vaccination rate was highest among children aged
<1year (43.8 per 100) and 5-9year-olds (6.9 per 100). There were salient
differences in immunization rates, including positive skin tests and
vaccinations, across administrative regions but no difference by sex. CONCLUSION:
This is the first comprehensive description of the tuberculosis prevention
program in Quebec which offered free, non-mandatory BCG vaccination. Our results
confirm that the targeted groups, newborns and school-age children, were
preferentially reached. Socioeconomic, demographic, and organizational factors
may explain regional differences in immunization rates. Beyond presenting a
historical context for this vaccination campaign, our findings are relevant to
contemporary uses of the Quebec BCG Vaccination Registry in epidemiological
research.
PMID- 28705515
TI - Combination vaccine strategies to prevent enteric infections.
AB - New vaccine candidates entering the current routine immunization schedule can
best be accommodated as combination vaccines. A combined Shigella and
enterotoxigenic E. coli (ETEC) vaccine could greatly benefit children in disease
endemic areas. New candidates are getting closer to being able to meet these
needs, but they raise numerous strategic questions related to presentation,
formulation, and regulatory approach. The "Combination Vaccine Strategies to
Prevent Enteric Infections" workshop at the 2016 Vaccines Against Shigella and
ETEC (VASE) Conference examined some of the considerations for developing such
vaccines against enteric pathogens.
PMID- 28705516
TI - Dermoscopy of Pigmented Actinic Keratosis of the Face: A Study of 232 Cases.
AB - : The diagnosis of pigmented actinic keratosis (PAK) is often challenging because
of overlapping features with lentigo maligna. OBJECTIVE: To investigate
dermoscopic patterns of PAK according to their different evolutionary stages, and
to correlate the pattern with clinical characteristics of the patients. METHODS:
Descriptive and analytical study of 232 PAK. Dermoscopic patterns were divided
into two categories: the follicule surroundings' abnormalities (FSA) and
follicular keratosis' abnormalities (FKA). RESULTS: FSA and FKA dermoscopic
patterns were related to male gender, except for star-like appearance, double
white clods and dermoscopic horn (p<=0.04). Rhomboidal, annular granular pattern,
gray halo, white circle and double clods were dermoscopic pattern significantly
related to xeroderma pigmentosum's type of skin. Based on the evolutionary stages
of PAK, the jelly sign was significantly related to thin patches of PAK. Central
crusts and scales were related to thick plaques and the star-like appearance to
hypertrophic PAK. The presence of 2 or more dermoscopic signs in both FSA and FKA
was noticed in 99.1% of lesions. CONCLUSIONS: The dermoscopic diagnosis of PAK
vary according to the evolutionary stages of the disease, this will increase the
diagnosis accuracy, with therapeutic implications.
PMID- 28705517
TI - Lichen Aureus: A Congenital Case?
PMID- 28705518
TI - Usefulness of ultrasound in the diagnosis and follow-up of pyoderma gangrenosum.
PMID- 28705519
TI - Acquired Port-Wine Stain (Fegeler Syndrome): A Report of 3 Cases.
PMID- 28705520
TI - Skin Cancer and the Dermatologist: Reflections on the Position Taken by the
Spanish Society of Medical Oncology (SEOM).
PMID- 28705521
TI - Multiple Epidermolytic Acanthomas on the Scrotum: What Genital Pruritus Can
Reveal.
PMID- 28705522
TI - Letter regarding the article: "A novel missense variant (Gln220Arg) of GNB4
encoding guanine nucleotide-binding protein, subunit beta-4 in a Japanese family
with autosomal dominant motor and sensory neuropathy".
PMID- 28705523
TI - Early volumetric changes after vertical augmentation of the atrophic posterior
mandible with interpositional block graft versus onlay bone graft: A
retrospective radiological study.
AB - PURPOSE: The aim of this study was to evaluate volumetric and clinical outcomes
of atrophic posterior mandibles treated with inlay or onlay bone grafting
techniques. MATERIALS AND METHODS: In posterior mandibles, alveolar ridges were
treated either with interpositional equine cancellous bone block (inlay group) or
with onlay autogenous bone block (onlay group). Bone volumes at baseline and at 4
months after surgery were measured by computed tomography. RESULTS: A total of 20
subjects were enrolled in the present study: 10 in the inlay group and 10 in the
onlay group. After surgery, atrophic posterior mandibles showed a mean vertical
augmentation height of 6.0 mm in the inlay group and 7.4 mm in the onlay group.
No significant differences were recorded between the two groups regarding volume
loss of the grafted bone or decrease in vertical bone height of the augmented
site (29% and 1.9 mm for the onlay group, and 35% and 1.7 mm for the inlay group)
during healing. Two complications (1 wound dehiscence and 1 mandibular fracture)
occurred postoperatively in the inlay group; on the other hand, the onlay group
had three complications (wound dehiscence). A total of 80 dental implants were
placed in augmented areas: 46 in the inlay group with a peri-implant marginal
bone loss of 0.8 mm, and 34 in the onlay group with a peri-implant marginal bone
loss of 1.3 mm (p = 0.0006). CONCLUSIONS: Inlay xenogeneic grafts showed
volumetric bone remodeling similar to that recorded for onlay autogenous bone.
The success of the autogenous onlay blocks (82.4%) appeared to be lower than that
registered for the inlay group (93.8%), but the difference was not significant.
PMID- 28705524
TI - Change Management-A Radiology Administrator's Primer.
AB - Radiology is no exception to the ubiquitous presence of change in every aspect of
our life. Managing change is a challenge, with a high probability of failure if
not properly implemented. While change management is not part of the radiology
curriculum, it is a highly specialized discipline in the business world. It has
been extensively researched and has emerged as a vital skillset in the management
of major projects. In this article, the authors discuss how these change
management strategies of the business world can be put to use in the
radiologists's practice.
PMID- 28705525
TI - The Top 100 Most-Cited Articles in Stroke Imaging: A Bibliometric Analysis.
AB - PURPOSE: The goal of our study was to compile a list of the top 100 most-cited
articles in stroke imaging literature across all peer-reviewed scientific
journals. These articles were then analyzed to identify current trends in stroke
imaging research and determine the characteristics of highly-cited articles.
MATERIALS AND METHODS: A database of the top 100 most-cited articles was created
using Scopus and Web of Science. Articles were reviewed for applicability by 2
fellowship-trained radiologists with over 10 years of combined experience in
neuroimaging. The following information was collected from each article: Article
Title, Scopus Citations, Year of Publication, Journal, Journal Impact Factor,
Authors, Number of Institutions, Country of Origin, Study Topic, Study Design,
and Sample Size. RESULTS: Citations for the top 100 most-cited articles ranged
from 159-810, and citations per year ranged from 5.7-516.0. Most of articles were
published between 1996 and 2000 (n = 43). Articles were published across 18
journals, most commonly in Stroke (n = 40). Magnetic resonance imaging was the
focus in 46 articles, computed tomogrphy in 16, and functional magnetic resonance
imaging in 10. The most common study topic is prognostic use of an imaging
modality (n = 27). CONCLUSIONS: Our study helps to characterize the field and
identify the characteristics of most-cited articles.
PMID- 28705526
TI - Utility of Single-Phase Computed Tomography in Identifying Parathyroid Adenomas:
A Feasibility Study.
AB - OBJECTIVE: We tested the hypothesis that a single-phase neck computed tomography
(CT) is not inferior to multiphase neck CT (MPNCT), ultrasound, or nuclear
medicine sestamibi scan in identifying parathyroid adenomas (PAs). METHODS: A
total of 29 patients who had an MPNCT for the evaluation of a PA were identified;
11 patients met the inclusion criteria. During the 30-second arterial phase CT
(APNCT), a normalized Hounsfield unit of suspected PA was compared to Hounsfield
unit of a normal-appearing level I and a level II lymph node. A PA was defined as
a lesion with a ratio of greater than 1.4 when compared to the level I and level
II lymph node. This cutoff was determined based on the normalized ratios between
level II and level I lymph nodes. Results of intraoperative parathyroid hormone
assays and surgical pathology were used to validate the accuracy of this
technique. RESULTS: The sensitivity of this method in APNCT is 90.9% whereas
positive predictive value is 100%. The sensitivity or positive predictive value
of ultrasound and nuclear medicine are 60% or 100% and 90% or 100%, respectively.
CONCLUSION: The sensitivity of APNCT is equivalent to that of MPNCT in
identifying PA.
PMID- 28705527
TI - Reducing STAT Portable Chest Radiograph Turnaround Times: A Pilot Study.
AB - BACKGROUND: Our health system orders a high number of STAT priority portable
chest radiographs (62%) compared to Routine (35%) and Today (3%). Retrospective
chart review of 1000 chest radiographs ordered with the STAT priority revealed
that 38% of studies did not indicate clinical urgency. Given the high number or
STAT priority portable chest radiographs ordered, prioritizing acquisition and
interpretation of true STATs has become challenging for technologists and
radiologists, leading to process inefficiencies, long turnaround times (TATs),
communication failures, and patient-safety errors. METHODS: A multidisciplinary
team analyzed the current pathway for exam order to finalized report, identified
failure modes of imaging order to completion process, and developed guidelines
for what constitutes a true STAT examination. A new "urgent" order category
meeting the definition of true STAT was designed, tested, and implemented over a
9-month period in participating intensive care units RESULTS: Since study
implementation, 108 "urgent" examinations were ordered. Median TAT for a STAT
examination from order entry to image acquisition dropped from 70 minutes
preimplementation to 16 minutes for "urgent" examinations. Median TAT for exam
completion to radiologist image interpretation dropped from 520 minutes
preimplementation to 14 minutes for "urgent" examinations. Since implementation,
"urgent" examinations were found to be more concordant (70%) with the status of a
critically ill patient than STAT examinations (62%). CONCLUSIONS: The complexity
of large multispecialty medical centers and lack of direct interaction of the
radiologist with clinicians has led to underappreciation of the needs of ordering
providers by radiology, and elucidated system limitations of radiology by
ordering providers. By involving a team of frontline clinicians, our team
standardized the process of identifying, ordering, procuring, interpreting, and
communicating results of true STAT examinations. The process created by our team
now serves as a template for implementation in other locations and service lines
of our hospital.
PMID- 28705528
TI - Implantation of Ventricular Assist Devices in Hypertrophic Cardiomyopathy. Is It
a Safe Option?
PMID- 28705529
TI - Atrial Fibrillation: A Riddle Wrapped in a Mystery Inside an Enigma.
PMID- 28705530
TI - Reperfusion Strategies in Hospitals Without Primary Percutaneous Coronary
Intervention.
PMID- 28705531
TI - Role of mitochondria and energy metabolism in schizophrenia and psychotic
disorders.
PMID- 28705532
TI - Kynurenine pathway in schizophrenia: Galantamine-memantine combination for
cognitive impairments.
PMID- 28705533
TI - Characterization and prediction of the backscattered form function of an immersed
cylindrical shell using hybrid fuzzy clustering and bio-inspired algorithms.
AB - The acoustic scattering of a plane wave by an elastic cylindrical shell is
studied. A new approach is developed to predict the form function of an immersed
cylindrical shell of the radius ratio b/a ('b' is the inner radius and 'a' is the
outer radius). The prediction of the backscattered form function is investigated
by a combined approach between fuzzy clustering algorithms and bio-inspired
algorithms. Four famous fuzzy clustering algorithms: the fuzzy c-means (FCM), the
Gustafson-Kessel algorithm (GK), the fuzzy c-regression model (FCRM) and the Gath
Geva algorithm (GG) are combined with particle swarm optimization and genetic
algorithm. The symmetric and antisymmetric circumferential waves A, S0, A1, S1
and S2 are investigated in a reduced frequency (k1a) range extends over
0.1=1 study-drug injection (600 radium-223 and 301 placebo). Patients
(405 radium-223 and 167 placebo) entered long-term safety follow-up starting 12
wk after the last study-drug injection, to 3 yr from the first injection. Forty
eight of 405 (12%) radium-223 and 12/167 (7%) placebo patients completed follow
up, with evaluations every 2 mo for 6 mo, then every 4 mo until 3 yr. OUTCOME
MEASUREMENTS AND STATISTICAL ANALYSIS: All adverse events (AEs) were collected
until 12 wk after the last injection; subsequently, only treatment-related AEs
were collected. Additional long-term safety was assessed by development of acute
myelogenous leukemia (AML), myelodysplastic syndrome (MDS), aplastic anemia, and
secondary malignancies. Data analysis used descriptive statistics. RESULTS AND
LIMITATIONS: During treatment to 12 wk following the last injection, 564/600
(94%) radium-223 and 292/301 (97%) placebo patients had treatment-emergent AEs
(TEAEs). Myelosuppression incidence was low. Grade 3/4 hematologic TEAEs in
radium-223 and placebo groups were anemia (13% vs 13%), neutropenia (2% vs 1%),
and thrombocytopenia (7% vs 2%). Ninety-eight of 600 (16%) radium-223 and 68/301
(23%) placebo patients experienced grade 5 TEAEs. Long-term follow-up showed no
AML, MDS, or new primary bone cancer; secondary non-treatment-related
malignancies occurred in four radium-223 and three placebo patients. One radium
223 patient had aplastic anemia 16 mo after the last injection. No other cases
were observed. Limitations include short (3-yr) follow-up. CONCLUSIONS: Final
long-term safety ALSYMPCA analysis shows that radium-223 remained well tolerated,
with low myelosuppression incidence and no new safety concerns. PATIENT SUMMARY:
Updated Alpharadin in Symptomatic Prostate Cancer (ALSYMPCA) trial findings show
that radium-223 remained well tolerated during treatment and up to 3 yr after
each patient's first injection.
PMID- 28705541
TI - Risk Factors Affecting Breast Cancer-related Lymphedema: Serial Body Weight
Change During Neoadjuvant Anthracycline Plus Cyclophosphamide Followed by Taxane.
AB - INTRODUCTION: The aim of our study was to analyze the risk of lymphedema (LE)
according to the clinicopathologic factors and to investigate the serial change
in body weight during neoadjuvant anthracycline plus cyclophosphamide followed by
taxane and its correlation with the incidence of LE. PATIENTS AND METHODS: We
performed a retrospective 2-center study of 406 patients who had undergone
neoadjuvant chemotherapy (NAC) followed by surgery from 2007 to 2014. The regimen
included 4 cycles of anthracycline plus cyclophosphamide, followed by 4 cycles of
taxane. We investigated the presence and degree of LE using a telephone
questionnaire assessment. Weight changes were calculated at each cycle of NAC,
and the baseline and preoperative body weights were used to calculate the rate of
change to account for the change in weight before and after NAC. RESULTS: Of the
406 patients, 270 answered the questionnaires, of whom 97 (35.9%) experienced LE.
The increase in body weight was significant during the 4 cycles of taxane, but
the change in weight was not significant during the 4 cycles of anthracycline
plus cyclophosphamide. The change in body weight was most significant just after
the fourth cycle of taxane (P < .001). The body mass index (BMI) was an
independent factor of LE occurrence on multivariate analysis. However, the change
in body weight was not a significant factor for the incidence of LE. CONCLUSION:
Because a BMI >= 25 kg/m2 was an independent factor of LE occurrence on
multivariate analysis, patients with a preoperative BMI >= 25 kg/m2 should be
closely monitored for LE given their increased risk, and monitoring and education
should be initiated before surgery and continued throughout the course of NAC.
PMID- 28705542
TI - Effect of Coronary Artery Disease risk SNPs on serum cytokine levels and cytokine
imbalance in Premature Coronary Artery Disease.
AB - BACKGROUND: Premature Coronary Artery Disease (PCAD) occurs almost a decade
earlier in the South Asian population as compared to the West. Inclusion of
genetic information can prove to be a robust measure to improve early risk
prediction of PCAD. Aim was to estimate the genotypic distribution and risk
allele frequencies of 13 Coronary Artery Disease (CAD) risk Single Nucleotide
Polymorphisms in loci identified by the CARDIoGRAMplusC4D consortium namely MIA3
rs17465637; 9p21 rs10757274; CXCL12 rs1746048; APOA5 rs662799; APOB rs1042031;
LPA rs3798220; LPA 10455872; MRAS rs9818870; LPL rs328; SORT1 rs646776; PCSK9
rs11591147; APOE rs429358; APOE rs7412 in Pakistani PCAD patients and controls.
Moreover, the differential serum cytokine levels (IL-18, IL-10, IL-6, TNF-alpha,
IL-18:IL-10 & TNF-alpha:IL-10 ratios) with respect to the genotypic distribution
of these selected SNPs were determined. MATERIAL AND METHODS: The case-control
study was carried out in National University of Sciences and Technology,
Islamabad in collaboration with the Cardiovascular Genetics Institute, University
College London, UK. Subjects (n=340) with >70% stenosis in at least a single
major coronary artery on angiography were taken as PCAD cases along with 310
angiographically verified controls. ELISA was performed for measuring the
concentrations of serum IL18, TNFA, IL6 and IL10. Genotyping was done using
TAQMAN and KASPar assays. RESULTS: The risk allele frequencies (RAF) of APOE
rs7412, CXCL12 rs1746048, 9p21 rs10757274, MIA3 rs17465637 and SORT1 rs646776
were significantly higher in the PCAD cases as compared to the controls. APOE
rs429358 had the greatest influence among the selected GWAS/CARDIoGRAMplusC4D
consortium CAD risk SNPs by significantly altering the serum levels of TNF-alpha,
IL-10 and TNF-alpha:IL-10 ratio. It was followed by APOE rs7412 and CXCL12
rs1746048 which significantly altered the serum levels of IL-18; TNF-alpha and IL
18; IL-18:IL-10 ratio respectively. The cytokine imbalance denoted by IL-18:IL-10
was significantly higher in the risk allele carriers MIA3 rs17465637 and CXCL12
rs1746048 while TNF-alpha:IL-10 ratio was significantly raised in the risk allele
carriers of APOE rs429358; MRAS rs9818870 and LPL rs328. CONCLUSION: The
association of the selected SNPs with differential serum cytokine levels
especially the cytokine imbalance points towards their potential causal role in
the immune inflammatory pathogenic pathway of PCAD.
PMID- 28705543
TI - Oral Multimodal Analgesia for Total Joint Arthroplasty.
AB - BACKGROUND: Oral multimodal analgesia for hip and knee arthroplasty is
increasingly used as part of enhanced recovery protocols designed to minimize
early postoperative pain and to facilitate early discharge, while minimizing
undesirable side effects related to single-agent opioid administration. METHODS:
This article is a review of previously published data evaluating the use of
various oral medications in the management of postoperative pain after lower
extremity arthroplasty and was presented as part of a symposium at the November
2016 AAHKS Annual Meeting. RESULTS: Multimodal analgesia has been shown to reduce
opioid consumption and side effects, with a positive effect on both early and
longer term outcomes for hip and knee arthroplasty patients. Medications directed
at multiple points on the pain cascade minimize pain by different mechanisms.
Suggested dosing regimens are proposed. CONCLUSION: Oral multimodal analgesia
incorporating a combination of opioid and nonopioid analgesics, selective and
nonselective anti-inflammatory drugs, acetaminophen, and gabapentinoids are
recommended as a part of a pre-emptive approach to pain management in patients
undergoing hip or knee arthroplasty. Reduction of opioid consumption and
minimization of side effects are primary outcomes, and prevention of chronic pain
can positively affect long-term results.
PMID- 28705544
TI - Response to Letter to the Editor on "Weight Gain After Primary Total Knee
Arthroplasty is Associated With Accelerated Time to Revision for Aseptic
Loosening".
PMID- 28705545
TI - Response to Letter to the Editor on "Physical Activity Promotes Gait Improvement
in Patients With Total Knee Arthroplasty".
PMID- 28705546
TI - A Comparative Study on the Long-Term Outcome of Total Knee Arthroplasty Performed
for Knees Stiff in Extension and Those Stiff in Flexion.
AB - BACKGROUND: Patients with chronic stiff knee with extremely restricted arc of
motion (AOM <= 20 degrees ) may present with stiffness either in extension (stiff
in extension [SE]) or in flexion (stiff in flexion [SF]). The difference in the
functional outcome after total knee arthroplasty between these 2 groups has not
been elaborated in literature. METHODS: We retrospectively analyzed 96 patients
(115 knees), who had undergone total knee arthroplasty between January 1990 and
December 2010 for stiff or spontaneously ankylosed knees (AOM <= 20 degrees ).
This included 51 knees in SE group and 64 knees in SF group. RESULTS: The average
duration of follow-up was 9.7 years (2-17.5 years). The total AOM improved from
an average of 10.9 degrees +/- 7.4 degrees preoperatively to 86.5 degrees +/-
13.5 degrees postoperatively in SE group and 8.7 degrees +/- 6.8 degrees to
92.2 degrees +/- 16.8 degrees in the SF group. The mean Knee Society Score in
the SE group improved from 23.2 +/- 5.7 preoperatively to 74.1 +/- 8.9
postoperatively and that of SF group from 14 +/- 5.2 to 71.2 +/- 12.5. At 3
months follow-up, Knee Society Score for SE group were higher than that for SF
group (P = .03). This difference was not noted beyond 1 year. Complications were
noted in 24 (20.9%) knees-10 (23.5%) in SE group and 14 (21.9%) in SF group.
CONCLUSION: The maximum mean AOM achieved was higher in SF group but the
incidence of residual flexion contracture was also higher as compared to SE
group. The long-term functional outcome scores in SE and SF groups are similar.
PMID- 28705547
TI - Closed Incision Negative Pressure Therapy Effects on Postoperative Infection and
Surgical Site Complication After Total Hip and Knee Arthroplasty.
AB - BACKGROUND: The aim of this study is to determine whether negative pressure wound
therapy, used prophylactically in clean surgical incisions, reduces surgical site
infection, hematoma, and seroma after total joint replacement. METHODS: A single
center, open-label study with a prospective cohort of patients undergoing primary
total knee arthroplasty or total hip arthroplasty treated with closed incision
negative pressure therapy (ciNPT) of clean surgical wounds was conducted. One
hundred ninety-six incisions treated with ciNPT in 192 patients were compared
with a historical control group of 400 patients treated with traditional gauze
dressing. The rates of clinically significant hematoma, seroma, dehiscence,
surgical site infection, and complication were compared using univariate analyses
and multiple logistic regression. RESULTS: The rate of deep infection was
unchanged in the ciNPT group compared with control (1.0% vs 1.25%); however, the
overall rate of infection (including superficial wound infection) decreased
significantly (3.5% vs 1.0%, P = .04). Overall complication rate was lower in the
ciNPT group than controls (1.5% vs 5.5%, P = .02). Upon logistic regression, only
treatment group was associated with complication; patients treated with ciNPT
were about 4 times less likely to experience a surgical site complication
compared with control (P = .0277, odds ratio 4.251, 95% confidence interval 1.172
15.414). CONCLUSION: ciNPT for total knee arthroplasty and total hip arthroplasty
in a comprehensive patient population reduced overall incidence of complication,
but did not significantly impact the rate of deep infection. Further research to
determine clinical and economic advantages of routine use of ciNPT in total joint
arthroplasty is warranted.
PMID- 28705548
TI - Age-dependent ventricular arrhythmias risk, structural and molecular remodeling
in systemic arterial hypertension.
AB - INTRODUCTION: The left ventricular hypertrophy (LVH)-ventricular arrhythmias
relationship associated with arterial hypertension and aging remains
controversial. We aimed to assess the age-dependency of ventricular arrhythmias
in spontaneously hypertensive rats (SHRs) and the corresponding ventricular
structural and molecular remodeling. MATERIALS AND METHODS: Ventricular
arrhythmias were quantified using 24-h radiotelemetry ECG monitoring in eight
SHRs and four Wistar-Kyoto (WKY) rats at 14 (young), 24 (adult), and 48 (aging)
weeks of age. Left ventricular histology and mRNA expressions of 89
proarrhythmogenic genes were assessed in six additional groups (n=4 each) of
young, adult, and aging SHRs and WKYs. RESULTS: Regardless of their age, SHRs
presented more premature ventricular contractions (PVCs) than age-matched WKYs
(p<0.01). The arrhythmogenicity peak occurred in adult SHRs; ventricular
tachycardias only occurred in adult SHRs. Among the SHRs, LV thickness,
interstitial fibrosis, and the number of deregulated genes increased with age.
Kcnj11 expression was deregulated in adult, but not in young or aging SHRs.
DISCUSSION: This study confirms the presence of higher ventricular ectopy in SHRs
than in age-matched WKYs. LVH appeared to be an adaptive, antiarrhythmic process.
Myocardial energetic changes with advancing age, as reflected by Kcnj11
expression changes, could underlie this age-dependency of ventricular
arrhythmias.
PMID- 28705549
TI - [Voluntary and non-remunerated blood donation; current situation and
perspectives].
AB - The voluntary and unpaid blood donation is recommended by all international
authorities (WHO, Council of Europe, ISBT, EBA), because it represents the best
way of aiming towards self-sufficiency in blood products of all kinds, while
preserving an optimal level of quality and safety for recipients as for donors.
Still infrequent in many developing countries it tends to develop. However, the
objective assigned by the WHO to reach 100% of unpaid and voluntary blood
donations in 2020 appears ambitious, in particular for the collection of plasma
intended to the splitting industry. The close evaluation of European directives
concerning the donation of human body elements should allow harmonization of
practices by Member States.
PMID- 28705550
TI - Tweeting celebrity suicides: Users' reaction to prominent suicide deaths on
Twitter and subsequent increases in actual suicides.
AB - A substantial amount of evidence indicates that news coverage of suicide deaths
by celebrities is followed by an increase in suicide rates, suggesting a copycat
behavior. However, the underlying process by which celebrity status and media
coverage leads to increases in subsequent suicides is still unclear. This study
collected over 1 million individual messages ("tweets") posted on Twitter that
were related to 26 prominent figures in Japan who died by suicide between 2010
and 2014 and investigated whether media reports on suicide deaths that generated
a greater level of reactions by the public are likely to be followed by a larger
increase in actual suicides. We also compared the number of Twitter posts and the
number of media reports in newspaper and on television to understand whether the
number of messages on Twitter in response to the deaths corresponds to the amount
of coverage in the traditional media. Using daily data from Japan's national
death registry between 2010 and 2014, our analysis found an increase in actual
suicides only when suicide deaths generated a large reaction from Twitter users.
In contrast, no discernible increase in suicide counts was observed when the
analysis included suicide deaths to which Twitter users did not show much
interest, even when these deaths were covered considerably by the traditional
media. This study also found suicides by relatively young entertainers generated
a large number of posts on Twitter. This sharply contrasts with the relatively
smaller volume of reaction to them generated by traditional forms of media, which
focuses more on the deaths of non-entertainers. The results of this study
strongly suggest that it is not sufficient to examine only traditional news media
when investigating the impact of media reports on actual suicides.
PMID- 28705551
TI - Effects of Progressive Resistance Training on Cardiovascular Autonomic Regulation
in Patients With Parkinson Disease: A Randomized Controlled Trial.
AB - OBJECTIVE: To evaluate the effects of a progressive resistance training (RT) on
cardiac autonomic modulation and on cardiovascular responses to autonomic stress
tests in patients with Parkinson disease (PD). DESIGN: Randomized clinical trial.
SETTING: The Brazil Parkinson Association. PARTICIPANTS: Patients (N=30) with PD
(modified Hoehn & Yahr stages 2-3) were randomly divided into 2 groups: a
progressive RT group (PD training [PDT] group) and a control group (PD control
[PDC] group). In addition, a group of paired healthy control (HC) subjects
without PD was evaluated. INTERVENTIONS: The PDT group performed 5 resistance
exercises, 2 to 4 sets, 12 to 6 repetitions maximum per set. Individuals in the
PDC group maintained their usual lifestyle. MAIN OUTCOME MEASURES: The PDT and
PDC groups were evaluated before and after 12 weeks. The HC group was evaluated
once. Autonomic function was assessed by spectral analysis of heart rate
variability and cardiovascular responses to autonomic stress tests (deep
breathing, Valsalva maneuver, orthostatic stress). RESULTS: Compared with
baseline, the normalized low-frequency component of heart rate variability
decreased significantly after 12 weeks in the PDT group only (PDT: 61+/-17
normalized units [nu] vs 47+/-20nu; PDC: 60+/-14nu vs 63+/-10nu; interaction
P<.05). A similar result was observed for systolic blood pressure fall during
orthostatic stress that also was reduced only in the PDT group (PDT: -14+/-11mmHg
vs -6+/-10mmHg; PDC: -12+/-10mmHg vs -11+/-10mmHg; interaction P<.05). In
addition, after 12 weeks, these parameters in the PDT group achieved values
similar to those in the HC group. CONCLUSIONS: In patients with PD, progressive
RT improved cardiovascular autonomic dysfunction.
PMID- 28705552
TI - An integrative data analysis of gender differences in children's understanding of
mathematical equivalence.
AB - This study examined gender as a potential source of variation in children's
formal understanding of mathematical equivalence. The hypothesis was that girls
would perform more poorly than boys. An integrative data analysis was conducted
with 960 second and third graders across 14 previously conducted studies of
children's understanding of mathematical equivalence. Measures included problem
solving, problem encoding, and equal sign definition. Overall, children performed
poorly on all measures. As predicted, girls were less likely than boys to solve
mathematical equivalence problems correctly, even though there were no gender
differences in calculation accuracy. In addition, girls were more likely than
boys to use the "add-all" strategy, an incorrect strategy that has been shown to
be more resistant to change than other incorrect strategies. There were not
statistically significant differences for encoding or defining the equal sign,
suggesting that deficits may reflect girls' tendency to follow taught algorithms.
PMID- 28705553
TI - Long-term outcomes after pancreaticoduodenectomy using pair-watch suturing
technique: Different roles of pancreatic duct dilatation and remnant pancreatic
volume for the development of pancreatic endocrine and exocrine dysfunction.
AB - BACKGROUND: We evaluated long-term outcomes including endo- and exocrine
functions after pancreaticoduodenectomy (PD) with standardized
pancreaticojejunostomy, paying attention to postoperative pancreatic duct
dilatation (PDD) and remnant pancreatic volume (RPV), and examined whether
postoperative pancreatic fistula (POPF) influenced the configuration of remnant
pancreas. METHODS: We analyzed the records of 187 patients with PD who could have
RPV measured by CT volumetry at 1 month after operation and had been followed for
more than 6 months. We assessed the risk factors of diabetes mellitus (DM) and
PDD, and evaluated association between RPV and pancreatic endo- and exocrine
functions assessed by several markers such as albumin, cholesterol, amylase and
HbA1c. RESULTS: Regarding RPV, pancreatic exocrine functions were significantly
impaired in the small-volume group (SVG: less than 10 ml) than in the large
volume group (LVG: 10 ml or more). The incidence of new-onset or exacerbation of
DM did not differ between SVG and LVG. PDD and the primary disease (pancreatic
ductal adenocarcinoma compared to bile duct cancer) were selected as the
independent risk factors of new-onset or exacerbation of DM by multivariate
analysis. Unexpectedly, there was no significant association between POPF and
PDD. CONCLUSIONS: Early occurrence of POPF after PD did not influence the
development of PDD in late period, and long-term follow-up should be made by
paying attention to PDD and RPV, because PDD was recognized as the most important
risk factor of new-onset or exacerbation of DM and the patients with small RPV
suffered from prolonged exocrine dysfunction rather than endocrine dysfunction.
PMID- 28705554
TI - Atrial function, atrial volume and cardiovascular clinical outcomes in patients
with end-stage renal disease - A study of cardiac computed tomography.
AB - BACKGROUND: Patients with chronic kidney disease (CKD) have an increased risk of
cardiovascular events. Previous studies using 2-dimensional echocardiography show
that left atrial end-diastolic volume (LAEDV) predicts cardiovascular outcomes
and mortality in patients with CKD. However, contrast-enhanced cardiac CT may
offers a more precise measure of atrial dimensions and function than 2
dimensional echocardiography and may provide improved predictionof patient
outcome. AIM: The aim of the present study was to examine the association of
LAEDV and left atrial ejection fraction (LAEF) assessed by CT with left ventricle
end-diastolic volume (LVEDV), left ventricular mass, left ventricular ejection
fraction and N-terminal plasma-pro-brain natriuretic peptide (NT-PRO-BNP).
Furthermore, we examined LAEDV and LAEF as predictors of major adverse cardiac
events (MACE) and mortality. METHODS: Kidney transplant candidates (n = 117)
underwent contrast-enhanced CT screening for coronary artery disease as part of
the work-up prior to kidney transplantation before being accepted on the
transplantation waiting list. Left atrial (LA) and left ventricular (LV) volume
and function were determined by cardiac CT. MACE and mortality data were
extracted from the Western Denmark Heart Registry, a review of patient records
and patient interviews. RESULTS: Baseline patient characteristics did not differ
between LAEDV tertiles. LAEDV was positively associated with measures of LV
function - both LVEDV (beta = 0.36, p < 0.05) and LV mass (beta = 0.30, p <
0.05). LAEF was not associated with measures of LV function. LAEDV was positively
and LAEF negatively associated with NT-PRO-BNP (LAEDV: beta = 10.28, p < 0.05.
LAEF: beta = -0.06, p < 0.05). During a median follow-up of 3.7-years, 19 (16.2%)
patients died and 19 (16.2%) patients suffered MACE. MACE and survival analysis
showed no relation to LAEDV or LAEF. CONCLUSIONS: Using contrast-enhanced CT, we
demonstrated a correlation between atrial and ventricular functional parameters.
However, we found no association with either LAEF or LAEDV or MACE and mortality
in this cohort of kidney transplant candidates.
PMID- 28705555
TI - Sonodynamic Therapy Based on Combined Use of Low Dose Administration of
Epirubicin-Incorporating Drug Delivery System and Focused Ultrasound.
AB - Sonodynamic therapy (SDT) is currently considered as one of the promising
minimally invasive treatment options for solid cancers. SDT is based on the
combined use of a sonosensitizer drug and high-intensity focused ultrasound
(HIFU) to produce cytotoxic reactive oxygen species (ROS) in and around
neoplastic cells. Anthracycline drugs, including epirubicin (EPI), have been well
known as effective sonosensitizers after interaction with focused ultrasound.
Recently a new anticancer drug delivery system (DDS), NC-6300, has been developed
that comprises EPI through an acid-labile hydrazone bond. In previous in vivo
studies, NC-6300 showed basic drug safety and an excellent concentration property
of EPI, and recently has been tested in clinical trials. For realizing minimally
invasive cancer treatment, the present study demonstrated the effectiveness and
feasibility of DDS-based SDT, which combined a small dose of NC-6300 and low
energy of HIFU in mouse models of colon cancer and pancreatic cancer.
PMID- 28705556
TI - Supersonic Shear Wave Imaging of the Spleen for Staging of Liver Fibrosis in
Rats.
AB - The goal of the work described here was to explore the cause of spleen stiffness
(SS) in hepatic fibrogenesis and evaluate the value of SS in liver fibrosis (LF)
staging. LF was induced with carbon tetrachloride (CCl4) in rats (n = 40).
Supersonic shear wave imaging and contrast-enhanced ultrasound were performed to
determine liver stiffness (LS), SS and splenic hemodynamics. SS, LS and free
portal pressure exhibited moderate correlations with fibrosis stage (r = 0.744
0.835, p < 0.001). Time-intensity curves of contrast-enhanced ultrasound for the
spleen were presented as decreasing peak intensity and slope of decrease, and
increasing time to peak. Splenic sinus dilation and congestion were observed on
histopathologic analysis. The area under the receiver operating characteristic
curve of SS was higher than that of LS for differentiating LF stages 0-2 from
stages 3-4 (Z = 2.293, p = 0.02). SS is a reliable diagnostic marker for the
assessment of LF in the CCl4 model, especially for severe fibrosis. Elevated
portal pressure is the cause of increasing SS.
PMID- 28705557
TI - Automatic Identification of the Optimal Reference Frame for Segmentation and
Quantification of Focal Liver Lesions in Contrast-Enhanced Ultrasound.
AB - Post-examination interpretation of contrast-enhanced ultrasound (CEUS) cineloops
of focal liver lesions (FLLs) requires offline manual assessment by experienced
radiologists, which is time-consuming and generates subjective results. Such
assessment usually starts by manually identifying a reference frame, where FLL
and healthy parenchyma are well-distinguished. This study proposes an automatic
computational method to objectively identify the optimal reference frame for
distinguishing and hence delineating an FLL, by statistically analyzing the
temporal intensity variation across the spatially discretized ultrasonographic
image. Level of confidence and clinical value of the proposed method were
quantitatively evaluated on retrospective multi-institutional data (n = 64) and
compared with expert interpretations. Results support the proposed method for
facilitating easier, quicker and reproducible assessment of FLLs, further
increasing the radiologists' confidence in diagnostic decisions. Finally, our
method yields a useful training tool for radiologists, widening CEUS use in non
specialist centers, potentially leading to reduced turnaround times and lower
patient anxiety and healthcare costs.
PMID- 28705558
TI - ?
PMID- 28705559
TI - ?
PMID- 28705560
TI - ?
AB - THE ISSUES IN THE TRANSITION FROM PAEDIATRICS TO ADULT MEDICINE: The transfer or
transition from paediatric care to adult medicine is, for a large number of
adolescents and young adults being monitored for a rare and/or chronic pathology,
as well as for the care teams, a critical period in their medical journey and in
their life. It is both an individual and a public health issue, with medical
economic consequences. At the hopital Necker-Enfants malades in Paris, a specific
programme has been implemented aimed at the patients and carers.
PMID- 28705561
TI - ?
AB - WHEN AN ADOLESCENT BECOMES AN ADULT, LEGAL ASPECTS: When it comes to medical
care, the move from minor to adult status is problematic, between the age of
puberty and the age of majority, which only allows decisions to be taken
independently. Medical law has evolved over the last few years, propelled by the
promotion of child rights. It gives more space for adolescents to decide about
their own health.
PMID- 28705562
TI - ?
AB - THE "DOUBLE TRANSITION" OF YOUNG PEOPLE AFFECTED BY CANCER.: Transition can refer
to the transfer of a patient from a paediatric institution to an adult
department, but it can also refer to the constitutive process of moving into
adulthood. Based on a sociological field survey carried out on devices dedicated
to adolescents and young adults affected by cancer in France, the impact of this
ambivalence on care practices can be assessed. The current paradoxes the medical
and care relationship is exposed to are thus identified.
PMID- 28705563
TI - ?
AB - THE CHILD-ADULT TRANSITION FOR PATIENTS SUFFERING FROM EATING DISORDERS.: Eating
disorders are chronic and evolutive psychiatric conditions which develop on a
continuum between childhood and adulthood. The transition between child,
adolescent and then adult care is a period of great vulnerability which may
induce drop-out and aggravation of symptoms. In the case of eating disorders in
particular, personalised transition programmes have been implemented in order to
provide this support.
PMID- 28705564
TI - ?
PMID- 28705565
TI - ?
AB - PARTICULAR FEATURES OF THE TRANSITION IN PAEDIATRIC ONCOLOGY: The transition from
paediatrics to adult medicine for young people who have been treated for
paediatric cancer presents specific issues. This is due to the previous
experience of cancer, the risk of sequelae which is still present despite
recovery and, finally, the specific links established between families and
paediatricians. These paediatricians must, therefore, look forwards and prepare
the transition throughout their supervision, in order to allow separation while
avoiding a break in follow-up.
PMID- 28705566
TI - ?
AB - THE TRANSITION OF CHILDREN AFFECTED BY CANCER, THE FAMILY PERSPECTIVE.: During
serious diseases in childhood such as cancer, the journey of the families is
staged in information and transition times, which are essential stages for
rebuilding family life. Support, orientation and proposals for a way forward are
necessary for patients or their families not to be left in destructive isolation.
Support actions for patients and their loved ones are implemented, particularly
by associations.
PMID- 28705567
TI - ?
AB - "THE PAEDIATRICS DEPARTMENT WAS OUR SECOND HOME".: At the age of a few months,
Yakub was diagnosed with congenital liver fibrosis then polycystic kidney
disease. He has been monitored regularly since then, and has had to be readmitted
on several occasions due to complications. Now, aged 15, he is waiting for a
liver transplant and is under the care of the adult hepatology department. The
transition from paediatrics to the adult services was prepared, in advance, with
him and his family. Yakub and his mother's account.
PMID- 28705568
TI - ?
AB - THE DIAGNOSIS OF HYPERACTIVITY DISORDER IN CHILDREN: Hyperactivity disorder in
children is the most commonly found syndrome in paedo-psychiatric clinics.
Children's professionals need to have clinical data on the subject. The
diagnostic process includes several components which allow care to be tailored to
each child.
PMID- 28705569
TI - ?
AB - SUPPORT FOR ADOPTED CHILDREN AND THEIR FAMILIES: The stress associated with the
initial abandonment is a significant risk factor in the quality of the child's
development and their attachment to their new parents. Family support is
essential in these situations. Nurses, in particular, play an essential role in
establishing the parent-child relationship.
PMID- 28705570
TI - ?
AB - PAEDIATRIC VENOUS ACCESS BEING ESTABLISHED BY ADULT SMUR TEAMS: Paediatric
perfusion during pre-hospital care is a major issue in the event of life
threatening emergencies. Access, often restricted, to backup specialising in
paediatrics, implies the existence of practices on protocols for the adult mobile
emergency and intensive care service (Smur) in partnership with paediatricians.
Paediatric perfusion practices were assessed in these teams. The results show the
presence of a paediatric protocol in the adult Smur teams is not very common.
Nursing practices seem to be evolving towards the recommendations, thanks to
technological advances such as the use of the intraosseous device.
PMID- 28705571
TI - Tunnel widening after ACL reconstruction with aperture screw fixation or all
inside reconstruction with suspensory cortical button fixation: Volumetric
measurements on CT and MRI scans.
AB - BACKGROUND: Tunnel widening after anterior cruciate ligament reconstruction
(ACLR) is influenced by the surgical and fixation techniques used. Computed
tomography (CT) is the most accurate image modality for assessing tunnel
widening, but magnetic resonance imaging (MRI) might also be reliable for tunnel
volume measurements. In the present study tunnel widening after ACLR using
biodegradable interference screw fixation was compared with all-inside ACLR using
button fixation, with tunnel volume changes being measured on CT and MRI scans.
STUDY DESIGN: Randomized controlled trial; Level of evidence, 2. METHODS: Thirty
three patients were randomly assigned to hamstring ACLR using a biodegradable
interference screw or all-inside cortical button fixation. CT and MRI scanning
were done at the time of surgery and six months after. Tunnel volume changes were
calculated and compared. RESULTS: On CT, femoral tunnel volumes changed from the
postoperative state (100%) to 119.8% with screw fixation and 143.2% with button
fixation (P=0.023). The changes in tibial tunnel volumes were not significant
(113.9% vs. 117.7%). The changes in bone tunnel volume measured on MRI were
comparable with those on CT only for tunnels with interference screws. Tibial
tunnels with button fixation were significantly underestimated on MRI scanning
(P=0.018). CONCLUSIONS: All-inside ACLR using cortical button fixation results in
increased femoral tunnel widening in comparison with ACLR with biodegradable
interference screw fixation. MRI represents a reliable imaging modality for
future studies investigating tunnel widening with interference screw fixation.
PMID- 28705572
TI - Compliance with a multidisciplinary team meeting's decision prior to bariatric
surgery protects against major postoperative complications.
AB - BACKGROUND: Good surgical practice guidelines in France state that patients
eligible for bariatric surgery must always be discussed at a multidisciplinary
team (MDT) meeting. OBJECTIVE: Describe MDT meetings and assess their possible
impact on the postoperative course. SETTING: University Hospital, France, public
practice. METHODS: From April 2009 to March 2013, we included all patients
reviewed in a MDT meeting before bariatric surgery. The primary endpoint was the
case validation rate. The secondary endpoints were the number of MDT meetings,
the number of submissions discussed or refused, outcomes in patients who
underwent surgery in another center after refusal, or deferral in our MDT
meeting. RESULTS: Forty-nine MDT meetings were held representing 1099 case files
(816 patients) that were discussed. Of the case files, 84.5% concerned first-line
surgery, 14% concerned second-line surgery, and 1.4% concerned third-line
surgery. Overall, 776 (70.6%) of these submissions were approved, accounting for
95% of the patients. Further investigation before a decision was required in
13.3%. Surgery was definitively refused in 1% (n = 11). For the 776 patients
having undergone surgery, the complication rate was 10.1%, the major complication
rate was 6%, and the reoperation rate was 3.2%. For the 11 patients for whom
bariatric surgery was refused, 7 patients underwent surgery in another center
(without MDT meetings). There were 4 postoperative complications (57.1%; 3 major
and 1 minor). CONCLUSION: The MDT meeting's decision is important for
standardizing the management of obese patients before bariatric surgery. MDT
meetings might help to reduce complication by optimizing patient selection and
preoperative care.
PMID- 28705573
TI - The Effects of Neoadjuvant Axitinib on Anthropometric Parameters in Patients With
Locally Advanced Non-metastatic Renal Cell Carcinoma.
AB - OBJECTIVE: To examine the effect that neoadjuvant axitinib for the treatment of
localized renal cell carcinoma has on body compartment composition. MATERIALS AND
METHODS: The study was based on a single-institution, single-arm clinical trial
that enrolled 24 patients with locally advanced non-metastatic biopsy-proven
clear cell renal cell carcinoma. Patients received axitinib orally for up to 12
weeks. Computed tomography scans were completed before the start of treatment,
after 7 weeks of treatment and at the completion of 12 weeks of treatment.
Patients underwent nephrectomy after axitinib treatment. The primary outcome of
the current study was change in body compartment composition. Secondary outcomes
included development of new-onset sarcopenia and changes in body weight. RESULTS:
A total of 23 patients had a complete set of imaging for evaluation, of which 19
(82.6%) lost weight. Median weight loss was 4.5 kg (P <.001). Seven patients
(30.4%) had sarcopenia before treatment, with an additional 5 (21.7%) developing
sarcopenia during treatment. Median decrease in skeletal muscle was 2.9 cm2/m2 (P
<.001), visceral adipose tissue was 4.9 cm2/m2 (P = .132), and subcutaneous
adipose tissue was 1.0 cm2/m2 (P = .043). Ten of the 16 patients (62.5%) without
baseline sarcopenia achieved a partial response, whereas only 1 of the 7 patients
(14.3%) with baseline pretreatment sarcopenia achieved a partial response (P =
.069). CONCLUSION: Neoadjuvant axitinib resulted in a decrease in skeletal muscle
and subcutaneous adipose tissue, as well as weight loss. Patients with baseline
sarcopenia tended to have a lower response rate to neoadjuvant axitinib.
PMID- 28705574
TI - Magnetic Resonance Imaging and Pelvic Fracture Urethral Injuries.
AB - Pelvic fracture urethral injuries (PFUI) are devastating lesions that lead to
fibrosis and urethral disruption, which result in recurrent strictures, urinary
incontinence, fistulae, and even erectile dysfunction, representing a management
problem for the urologist. Magnetic resonance imaging (MRI) may be a valuable
tool in establishing or confirming the diagnosis by providing detailed anatomy
and estimating disease extent. We present a comprehensive review of the current
literature on the role of MRI on diagnostic evaluation and surgical management of
patients with PFUI.
PMID- 28705575
TI - Can a Simplified 12-Hour Nighttime Urine Collection Predict Urinary Stone Risk?
AB - OBJECTIVE: To determine if there is correlation between nighttime 12-hour and
traditional 24-hour urine collection in regard to chemistry values and the
supersaturations of calcium oxalate, calcium phosphate, and uric acid for the
metabolic evaluation of nephrolithiasis. MATERIALS AND METHODS: Ninety-five
patients were prospectively enrolled from 2013 to 2015. Patients >18 years of age
who presented to a tertiary stone clinic and who would normally be counseled for
24-hour urine collection were eligible for the study. Participants completed 24
hour urine collections twice, with each divided into 2 separate 12-hour
collections. Day-time collection began after the first morning void and continued
for 12 hours. The night collection proceeded for the next 12 hours through the
first morning void. RESULTS: Forty-nine 24-hour samples from 35 patients met
inclusion criteria and were included in the analysis. Overall, there was strong
correlation between the night 12-hour and the 24-hour urine collections with R2
ranging from 0.76 for pH to 0.96 for Citrate. In our analysis of variability, the
nighttime 12-hour collection differed from the 24-hour collection by 30% in 1-9
patients (2.0%-18.4%) based on individual chemistry value. Diagnosis of
underlying metabolic abnormalities was concordant in 92% of patients. CONCLUSION:
A 12-hour nighttime collection has strong correlation with 24-hour urine
collection. As such, simplifying the metabolic evaluation to a 12-hour overnight
collection may be feasible-improving compliance and decreasing patient burden.
PMID- 28705576
TI - Scrotal Ultrasound for Pain: Low Frequency of Absolute Surgical Indications.
AB - OBJECTIVE: To examine the results of scrotal ultrasounds (US) conducted for
scrotal or testicular pain and review the pathologic findings of orchiectomies
done for lesions that were suspicious for malignancy on US. MATERIALS AND
METHODS: We retrospectively reviewed the indications and findings of all scrotal
US completed at our institution from 2002 to 2014. If a patient underwent an
orchiectomy for an intratesticular lesion that was concerning for malignancy on
US, the pathology report was also reviewed. RESULTS: There were 18,593 scrotal US
performed, with 7,668 (41.2%) conducted for scrotal pain. Of the US performed for
pain, 80.4% revealed benign or normal findings, and only 2.2% demonstrated a
finding that is an absolute indication for surgery (intratesticular lesion
suspicious for malignancy 0.8%, abscess 0.7%, torsion 0.6%, infiltrative process
such as lymphoma 0.1%). For those patients undergoing an orchiectomy, 75% had
malignancy on pathologic analysis. CONCLUSION: The majority of the 7668 US
performed to evaluate scrotal or testicular pain reveal normal or benign
findings. A low percentage demonstrates a finding that necessitates urgent or
emergent surgery.
PMID- 28705577
TI - Comparative Evaluation of Bladder-specific Health-related Quality of Life
Instruments for Bladder Cancer.
AB - OBJECTIVE: To compare 2 bladder cancer-specific health-related quality of life
instruments (HRQOL) in the same patient population. Previous HRQOL studies in
cystectomy patients have yielded conflicting results. Using a cross-sectional
study design, we examined the only 2 validated bladder cancer-specific (HRQOL)
measures. METHODS: Of the 256 patients who had undergone radical cystectomy from
2009 to 2014, 131 met both inclusion and exclusion criteria. The Functional
Assessment Cancer Therapy-Vanderbilt Cystectomy Index (FACT-VCI) and Bladder
Cancer Index (BCI) were mailed to these patients. Overall HRQOL and individual
domain scores were compared between the 2 instruments with a Spearman correlation
coefficient. HRQOL scores were compared by urinary diversion type as well using a
non-parametric Wilcoxon rank sum test. RESULTS: Our study had a response rate of
49% from 31 ileal conduit (IC) and 33 orthotopic neobladder patients. Overall,
there was a moderate correlation between the FACT-VCI and BCI surveys (r = 0.57,
P <.001). Responses on the BCI domains were strongly correlated with responses on
the bladder cancer-specific domain of the FACT-VCI (r = 0.74, P <.001). The BCI
scores for urinary function were significantly better in the IC group (P = .002).
No significant difference was found between IC and orthotopic neobladder using
the FACT-VCI. CONCLUSION: The FACT-VCI and BCI instruments correlate well within
the same patient cohort but capture different aspects of HRQOL. By focusing
exclusively on bladder cancer treatment concerns, the BCI appears to be a better
tool for assessing and counseling patients on expected treatment-specific changes
after diversion type.
PMID- 28705578
TI - Cloacal Duplication: Single-center Experience in the Management of a Rare
Anomaly.
AB - Cloacal duplication is an exceedingly rare group of anomalies with a limited
number of cases reported so far. The anomaly may be confined to partial bladder
duplication or it may involve complete duplication of the urogenital tract,
hindgut, spine, lower limbs, and vascular structures. Every case is unique and
ought to be approached individually. By means of imaging studies and endoscopy,
anatomic details should be carefully defined before endorsing surgical
correction. A satisfactory outcome can be achieved in the majority of cases. In
this report, we describe 3 girls with cloacal duplication, and review pertinent
imaging and surgical management.
PMID- 28705579
TI - Melamine Poisoning Pediatric Urolithiasis Treatment in Gansu, China 5-Year Follow
up Analysis.
AB - OBJECTIVE: To investigate the clinical characteristics of urolithiasis,
retrospectively, in children who ingested melamine-poisoned formula as infants,
and report a 5-year follow-up analysis. MATERIALS AND METHODS: Clinical data on
207 patients (mean +/- standard deviation, 13.6 +/- 8.0 months) with melamine
induced urolithiasis were retrospectively analyzed. Patients were subdivided into
2 groups according to treatment. A 5-year follow-up study was conducted with
95.7% (198 of 207) of the children. Ultrasonography, renal function evaluation,
and urinalysis were analyzed. RESULTS: A total of 149 (72.0%) patients accepted
conservative treatment. Fifty-eight (28.0%) patients accepted surgical
intervention after conservative treatment proved ineffective. Of the 48 patients
in whom retrograde ureteral catheterization was performed, 33 discharged the
stone successfully, 4 had residual stones, 2 were switched to percutaneous
nephrolithotripsy, and 9 underwent ureteroscopic lithotripsy. Six patients
underwent extracorporeal shock wave lithotripsy, and other 4 patients underwent
ureteral lithectomy. The age of onset, clinical presentations, size and location
of stones, renal function, and mean time of hospitalization in patients with
surgical intervention were significantly different from those of patients who
accepted conservative treatment only (P < .001). The main component of the 12
melamine-contained stone samples was urate. The results of 5-year follow-up (mean
+/- standard deviation, 72.7 +/- 4.1 months) study in 198 children did not show
any significant difference of stone residue, renal function, and urinalysis
between 2 groups. CONCLUSION: If the stones were treated appropriately in
patients with melamine-induced urolithiasis, there is no medium-term risk for
stone formation. Still, a longer time follow-up study is required to determine if
there is any long-term poisonous effect on these patients.
PMID- 28705580
TI - Relationship between serum dioxin-like polychlorinated biphenyls and post
testicular maturation in human sperm.
AB - The relationship between dioxin-like polychlorinated biphenyl (DL-PCB) levels in
serum and semen parameters were investigated. Our case-control included two
groups of patients. Total concentrations of PCBs were significantly higher in the
low semen quality (n=24) than in the normal semen quality (n=26) group. A
significant negative correlation was found between PCB 126 and viability in men
with low semen quality, while PCBs 77 and 81 were positively correlated with
morphology, and PCB 118, mono-ortho and total DL-PCBs were positively correlated
with volume. In the normal semen quality group, PCB 189 and 118 were negatively
correlated with sperm motility and volume, respectively. In addition, positive
significant correlations were found between PCB 77, 23 and total non-ortho PCBs
with regard to morphology. Our findings suggest that sperm motility, viability,
volume and morphology are parameters sensitive to alteration by exposure to DL
PCBs, although PCB effects on spermatogenesis were not of clinical significance.
PMID- 28705581
TI - The influence of preprandial insemination on feeding and oviposition of Ixodes
persulcatus females (Acari: Ixodidae) and some thoughts concerning mating
strategies in ticks of the genus Ixodes.
AB - Prostriate ticks (subfamily Ixodinae, genus Ixodes) can copulate and the females
can be inseminated before attachment to the host. In tests with Ixodes
persulcatus females collected in the field and fed without males on the host, it
was shown that this preprandial insemination is necessary and sufficient for
successful engorgement and oviposition if female feeding took place in up to 1
month after collection. A 2-month period between preprandial insemination and
female feeding was followed by a significant decrease in the proportion of
normally engorged females and significant increase in egg mortality. If a small
number of males were added to feeding females in this case, the number of
normally engorged females increased but the egg mortality remained as high.
Spermatophore destruction during the 2-month period is assumed to have a negative
effect on the viability of eggs produced after additional (perprandial)
insemination. Prostriate ticks are believed to be an intermediate group between
argasid and metastriate ticks. Transition from nidicolous parasitism in argasid
ticks to exophily (pasture parasitism) in metastriate ticks determines the change
in mating strategy from off-host to on-host copulation. We review the available
data concerning mating strategies in representatives of different subgenera of
the genus Ixodes in the context of this evolutionary relationship.
PMID- 28705582
TI - Polymorphisms in sex steroid receptors: From gene sequence to behavior.
AB - Sex steroid receptors have received much interest as potential mediators of human
behaviors and mental disorders. Candidate gene association studies have
identified about 50 genetic variants of androgen and estrogen receptors that
correlate with human behavioral phenotypes. Because most of these polymorphisms
lie outside coding regions, discerning their effect on receptor function is not
straightforward. Thus, although discoveries of associations improve our ability
to predict risk, they have not greatly advanced our understanding of underlying
mechanisms. This article is intended to serve as a starting point for
psychologists and other behavioral biologists to consider potential mechanisms.
Here, I review associations between polymorphisms in sex steroid receptors and
human behavioral phenotypes. I then consider ways in which genetic variation can
affect processes such as mRNA transcription, splicing, and stability. Finally, I
suggest ways that hypotheses about mechanism can be tested, for example using in
vitro assays and/or animal models.
PMID- 28705583
TI - Prevalence and risk factors for colonization by Clostridium difficile and
extended-spectrum beta-lactamase-producing Enterobacteriaceae in rehabilitation
clinics in Germany.
AB - BACKGROUND: Rehabilitation clinics may vary widely in terms of type of care
provided, duration of hospital stay, and case severity. Few data are available on
prevalence of Clostridium difficile or extended-spectrum beta-lactamase-producing
Enterobacteriaceae (ESBL-E) colonization in rehabilitation clinics in Germany.
AIM: This study investigated the frequency of intestinal colonization by these
pathogens among patients in rehabilitation clinics of different specialization.
METHODS: In the scope of a point prevalence study, faecal samples and demographic
and clinical data were collected in five rehabilitation clinics. Samples were
screened for C. difficile and ESBL-E by culture. Isolates were characterized by
polymerase chain reaction for C. difficile toxins A and B, for beta-lactamase
genes, and by molecular typing including pulsed-field gel electrophoresis and PCR
based ribotyping. FINDINGS: Of 305 patients screened, 11.1% were colonized by
toxigenic C. difficile and 7.5% by ESBL-E. Colonization rates differed markedly
between facilities, ranging from 1.6% to 26.3% for C. difficile and from zero to
23.7% for ESBL-E. Prevalence of colonization by C. difficile and ESBL-E was
higher in neurological rehabilitation clinics than in clinics with other
specialties (P<0.001). Molecular typing revealed six patients from one
neurological rehabilitation clinic harbouring a unique C. difficile strain
(ribotype 017). CTX-M-15 was the most prevalent ESBL type. We detected several
indistinguishable pairs of ESBL-E isolates within some facilities. CONCLUSION:
Significant differences were found in the prevalence of C. difficile and ESBL-E
between rehabilitation clinics. Facilities providing specialized medical care for
critically ill patients had higher prevalence rates. These results may help to
delineate the requirements for infection prevention and control in rehabilitation
clinics.
PMID- 28705584
TI - Allergic bronchopulmonary aspergillosis treated successfully with omalizumab.
PMID- 28705585
TI - A four dimensional separation method based on continuous heart-cutting gas
chromatography with ion mobility and high resolution mass spectrometry.
AB - A two-dimensional GC (2D-GC) method was developed and coupled to an ion mobility
high resolution mass spectrometer, which enables the separation of complex
samples in four dimensions (2D-GC, ion mobilility spectrometry and mass
spectrometry). This approach works as a continuous multiheart-cutting GC-system
(GC+GC), using a long modulation time of 20s, which allows the complete transfer
of most of the first dimension peaks to the second dimension column without
fractionation, in comparison to comprehensive two-dimensional gas chromatography
(GCxGC). Hence, each compound delivers only one peak in the second dimension,
which simplifies the data handling even when ion mobility spectrometry as a third
and mass spectrometry as a fourth dimension are introduced. The analysis of a
plant extract from Calendula officinales shows the separation power of this four
dimensional separation method. The introduction of ion mobility spectrometry
provides an additional separation dimension and allows to determine collision
cross sections (CCS) of the analytes as a further physicochemical constant
supporting the identification. A CCS database with more than 800 standard
substances including drug-like compounds and pesticides was used for CCS data
base search in this work.
PMID- 28705586
TI - Capillary zone electrophoresis determination of aniline and pyridine in sewage
samples using transient isotachophoresis with a system-induced terminator.
AB - Transient isotachophoresis (tITP) with a system-induced terminator (SIT) was
developed for capillary zone electrophoresis (CZE) determination of aniline (An+)
and pyridine (Py+) in sewage samples. After sample injection, a water vial was
set at the sample-inlet side. Then voltage was applied to generate a system
induced terminator (H+). Experiments and simulations revealed a concentration
effect by tITP with an SIT: background electrolyte (BGE) - 100mM acetic acid
(AcOH) and 50mM NaOH (pH 4.6); detection wavelength - 200nm for An+ and 254nm for
Py+; vacuum injection period - 15s (190nL); SIT generation - 10kV applied for 80s
with the sample inlet side anode; separation voltage - 20kV with the sample inlet
side anode. The limits of detection (LODs, S/N=3) of An+ and Py+ respectively
reached 10 and 42MUg/L, with good repeatability (peak area RSDs<=6.9%) and
calibration graph linearity (R2=0.9997). The proposed method was applied for
determination of An+ and Py+ in sewage samples. Recoveries of An+ (0.50mg/L) and
Py+ (2.0mg/L) in spiked sewage samples were 94-104%.
PMID- 28705587
TI - Diagnosis of Parkinson's disease and the level of oxidized DJ-1 protein.
AB - Parkinson's disease (PD) is difficult to distinguish from progressive
supranuclear palsy (PSP) and multiple system atrophy (MSA); in addition,
biomarker studies in PD mostly focused on those found in the cerebrospinal fluid,
and there are few reports of simple biomarkers identified by blood analysis.
Previously, the DJ-1 gene was identified as a causative gene of familial PD.
Oxidized DJ-1 protein (oxDJ-1) levels were reported to increase in the blood of
patients with unmedicated PD. Therefore, we determined the levels of oxDJ-1 in
the erythrocytes of patients with PD, PSP, and MSA using ELISA. The oxDJ-1 levels
were 165+/-117, 96+/-78, and 69+/-40ng/mg protein in the PD, PSP, and MSA groups,
respectively. The mean level in disease control group was 66+/-31, revealing
significant differences between the PD and PSP groups, the PD and MSA groups, and
the PD and disease control groups. Our results indicated that oxDJ-1 levels in
erythrocytes can be used as a marker for the differential diagnosis of PD.
PMID- 28705588
TI - Elevated uric acid and adenosine triphosphate concentrations in bronchoalveolar
lavage fluid of eosinophilic pneumonia.
AB - BACKGROUND: Recent evidence has suggested that the innate immune response may
play a role in the development of eosinophilic airway inflammation. We previously
reported that uric acid (UA) and adenosine triphosphate (ATP), two important
damage-associated molecular pattern molecules (DAMPs), activate eosinophil
functions, suggesting that these molecules may be involved in the development of
eosinophilic airway inflammation. The objective of this study was to measure the
concentrations of DAMPs including UA and ATP in the bronchoalveolar lavage fluid
(BALF) of patients with eosinophilic pneumonia (EP). METHODS: BAL was performed
in patients with EP including acute and chronic eosinophilic pneumonia, and in
patients with hypersensitivity pneumonia, and sarcoidosis. UA, ATP, and cytokine
concentrations in the BALF were then measured. RESULTS: The UA concentration was
increased in the BALF of EP patients. UA concentrations correlated with
eosinophil numbers, and with eosinophil-derived neurotoxin and interleukin (IL)-5
concentrations. Furthermore, the ATP concentration was increased in the BALF of
EP patients and ATP concentrations correlated with UA concentrations. Moreover,
IL-33 was increased in EP patients and IL-33 concentrations correlated with UA
and ATP concentrations. CONCLUSIONS: The UA and ATP concentration was increased
in the BALF of EP patients. UA concentrations correlated with eosinophil numbers,
and with ATP and IL-33 concentrations. Our findings suggest that DAMPs such as UA
and ATP play a role in the pathogenesis of EP.
PMID- 28705589
TI - A simple technique for the correction of maxillonasal dysplasia using customized
expanded polytetrafluoroethylene (ePTFE) implants.
AB - BACKGROUND: The treatment of maxillonasal dysplasia in Binder's syndrome using
autologous costal bone and cartilage is well established, but postoperative
results may be compromised by scarring, unpredictable absorption of transferred
autologous tissue, and donor site morbidity. Here, we propose a simple surgical
technique to improve maxillonasal dysplasia using an expanded
polytetrafluoroethylene (ePTFE) implant. MATERIALS AND METHODS: From February
1999 to May 2014, fifty-eight patients affected by maxillonasal dysplasia with
different degrees of flattened nose and midfacial depression underwent surgical
correction by augmentation of the nasal dorsum using an "L"-shaped ePTFE and
subperiosteal implantation of an inverted "m"-shaped ePTFE at the base of the
piriform aperture. The outcome was evaluated based on preoperative and
postoperative patient pictures, 3D imaging technology for the assessment of
nasolabial angle and facial convexity angle, and a postoperative patient
satisfaction survey. RESULTS: Postoperative results showed improved facial
aesthetics with a significantly increased nasolabial angle from initially 74.1
degrees +/- 8.9 degrees to 93.7 degrees +/- 6.1 degrees at 6 months
postoperatively (p < 0.05). Temporary discomfort involving upper lip numbness,
foreign body sensation, and stiff smiling expression were complained during the
first 3 months postoperatively, but spontaneously resolved within 6 months.
Complications included infection (2 cases), implant migration (2 cases), and
implant exposure (1 case). The vast majority of patients (95.7%) rated their
postoperative outcome as highly improved and improved. CONCLUSION: The present
therapeutic strategy provides a simple and effective treatment for the correction
of maxillonasal dysplasia with high patient acceptance in a single step approach.
Further research is required to determine long-term outcomes.
PMID- 28705590
TI - Comparative study of type B distal radius fractures with and without lunate facet
involvement treated by volar locking plate, an observational study.
AB - PURPOSE: This study aimed to evaluate the results of volar locking plate for
treatment of type B distal radius fractures involving the lunate facet and
compare them with those without involvement in lunate facet. METHOD: s: This was
a retrospective study. A total of 93 patients with type B distal radius were
treated by single volar locking plate between January 2014 and December 2015.
Preoperative digital radiographs were used to initially diagnose and further
classify this injury according to AO/OTA classification system. CT scanning or
reconstruction was used to diagnose the complex or suspicious cases. Patients
with lunate facet involvement were defined as group 1 (n = 21) and the remaining
without luante facet involvement as group 2 (n = 72). Postoperative immediate
radiographs and radiographs at last visit were analyzed. We evaluated clinical
outcomes at minimum of 12 months and performed statistical analysis using the
SPSS 19.0 software package. RESULTS: Bony union was reached in all participants,
at the median time of 8 weeks. At the final follow-up, there were no significant
difference observed in term of volar tilt and radial inclination between both
groups (P, 0.172; 0.514). Articular step-off in group 1 was significantly greater
than those of group 2 (P, 0.016). Significant articular step-off (>2 mm) occurred
in 4 patients (19.0%) in group 1 and 3 (4.2%) in group 2 (P = 0.044). At 3-months
postoperatively, group 1 showed worse results than group 2 for most variables (P
< 0.05). At 6-months postoperatively, the differences for wrist flexion,
supination, ulnar deviation and VAS in motion remained significant between both
groups (P < 0.05). At the last follow-up, no significant differences were
observed for any variable (P > 0.05). Five minor complications occurred in group
1 and 11 in group 2, and the difference was not significant (P = 0.346).
CONCLUSIONS: Patients with distal radius fractures involving lunate facet would
obtain more slow recovery, especially for wrist flexion, supination, ulnar
deviation and VAS in motion. In addition, patients with lunate facet fractures
would be at higher risk of loss of reduction and final articular step-off.
PMID- 28705591
TI - Effectiveness of surgery versus conservative treatment for lumbar spinal
stenosis: A system review and meta-analysis of randomized controlled trials.
AB - PURPOSE: Lumbar spinal stenosis (LSS) was a common degenerative disease that
affected the lumbar spine function and quality of life, which can be treated both
surgery and conservative treatment. We did this study to compare the
effectiveness of surgery versus conservative treatment for LSS. METHODS: We
searched PubMed as well as other databases in September.18th.2016. Randomized
controlled trials compared surgery versus conservative treatment for patients
with LSS were enrolled. Outcomes and complications were collected with data
selection criteria and analyzed with Review Manager Version 5.3. RESULTS: Nine
RCTs (14 articles) and 1658 patients were included, and three of them were high
quality studies. At first 6 months after treatment, there were no significant
differences for ODI scores between two therapeutic groups (P > 0.05), however,
surgery group showed significant higher ODI scores at one year (P < 0.05) and two
years (P < 0.05). Two studies reported no significant difference between
laminectomy and conservative treatment for the SF-36 physical function scores at
3 months, 6 months, 12 months and 24 months (P > 0.05) and two studies reported
patients were satisfied with X-STOP implanted at six weeks, six months, and one
year. No statistical differences for the adverse events intra-operation or within
72 h (P > 0.05) between surgery and non-surgery groups. Moreover, subgroup
analysis showed there were no safety differences between laminectomy and
conservative treatment, X-STOP and conservative treatment at early stage of
duration. However, the surgical groups had higher complication rates than non
surgery groups throughout the follow-up duration. CONCLUSION: Surgery groups
showed better late clinical outcomes after one year and higher complication rate
throughout the follow-up duration, although it had no significant differences
compared with conservative groups in the first six months post-treatment.
However, there was no evidence that a definitive method could be firmly
recommended to LSS patients. Further researches were needed to achieve high
quality and credible results.
PMID- 28705592
TI - Effect of perioperative intravenous lidocaine infusion on postoperative recovery
following laparoscopic Cholecystectomy-A randomized controlled trial.
AB - BACKGROUND AND OBJECTIVE: Intravenous lidocaine infusion has been shown to
facilitate postoperative recovery after major abdominal surgery. The current
randomized controlled study was performed to assess the effect of perioperative
intravenous lidocaine infusion on pain intensity, bowel function and cytokine
response after larparoscopic cholecystectomy. METHODS: Eighty patients undergoing
laparoscopic cholecystectomy were randomly allocated to receive intravenous
lidocaine (bolus injection of 1.5 mg/kg lidocaine at induction of anesthesia,
then a continuous infusion of 2 mg/kg/h until the end of surgery) or an equal
volume of saline. Patients, anesthesiologists, and study personnel were blinded,
and anesthesia and multimodal perioperative analgesia were standardized. Blood
cytokines were measured at scheduled times within 48 h. Pain scores, opioid
consumption, time to first flatus and time to first bowel movement were also
measured after surgery. RESULTS: Seventy-one of the 80 patients who were
recruited completed the study protocol. Patient demographics were similar in the
two groups. Lidocaine significantly reduced pain intensity [visual analogue scale
(VAS), 0-10 cm] at 2 h (lidocaine 3.01 +/- 0.65 cm vs. placebo 4.27 +/- 0.58 cm,
p = 0.01) and 6 h (lidocaine 3.38 +/- 0.42 cm vs. placebo 4.22 +/- 0.67 cm, p =
0.01) and total fentanyl consumption 24 h after surgery (lidocaine 98.27 +/-
16.33 MUg vs. placebo 187.49 +/- 19.76 MUg, p = 0.005). Time to first flatus
passage (lidocaine 20 +/- 11 h vs. placebo 29 +/- 10 h, p = 0.01) and time to
first bowel movement (lidocaine 41 +/- 16 h vs. placebo 57 +/- 14 h, p = 0.01)
were also significantly shorter in patients who received lidocaine. Intravenous
lidocaine infusion experienced less cytokine release than the control group.
CONCLUSIONS: This study indicates that perioperative systemic lidocaine improves
postoperative recovery and attenuates the initiation of excessive inflammatory
response following laparoscopic cholecystectomy.
PMID- 28705593
TI - Parallel placement of Excluder legs for treatment of type IIIb endoleaks caused
by fabric tear after endovascular aneurysm repair.
AB - A total of 576 patients underwent endovascular aneurysm repair using main body
devices for treatment of abdominal aortic aneurysms or iliac artery aneurysms.
During follow-up, type IIIb endoleaks caused by fabric tear occurred in six
patients (1.0% [6/576]). The device used was Zenith (Cook Medical, Bloomington,
Ind) in five cases and Talent (Medtronic, Santa Rosa, Calif) in one case. All
endoleaks were close to the flow divider of the main body devices. The distance
between the lower renal artery and the top end of the contralateral leg was 53 +/
14 mm. Bell-bottom-shaped Excluder (W. L. Gore & Associates, Flagstaff, Ariz)
legs were placed parallel from the top of the main body device through both legs
to treat these endoleaks. In two patients, coil embolization was required to
treat gutter endoleaks. Postoperative computed tomography showed the obliteration
of type IIIb endoleaks in all patients. Our technique may be an acceptable method
for treatment of type IIIb endoleaks, especially when they occur near the flow
divider.
PMID- 28705594
TI - Induction of ABCG2/BCRP restricts the distribution of zidovudine to the fetal
brain in rats.
AB - Safety concerns for fetus development of zidovudine (AZT) administration as
prophylaxis of vertical transmission of HIV persist. We evaluated the
participation of the ATP-binding cassette efflux transporter ABCG2 in the
penetration of AZT into the fetal brain and the relevance for drug safety. Oral
daily doses of AZT (60mg/kg body weight) or its vehicle were administered between
post gestational days 11 (E11) and 20 (E20) to Sprague-Dawley pregnant rats. At
E21, animals received an intravenous bolus of 60mg AZT/kg body weight in the
presence or absence of the ABCG2 inhibitor gefitinib (20mg/kg body weight, ip)
and AZT in maternal plasma and fetal brain were measured by HPLC-UV. ABCG2
protein expression in placenta and fetal brain, as well as mitochondrial function
and ultrastructure in fetal brain were also analyzed. In utero chronic exposure
to AZT markedly induced ABCG2 expression in placenta and fetal brain whereas did
not significantly alter mitochondrial functionality in the fetal brain. The area
under-the-concentration-time-curve of AZT significantly decreased in fetal brains
isolated from AZT-exposed fetuses compared to control group, but this effect was
abolished by ABCG2 inhibition. Our results suggest that the absence of
mitochondrial toxicity in the fetal brain after chronic in utero administration
of AZT could be attributed to its low accumulation in the tissue caused, at least
in part, by ABCG2 overexpression. We propose that any interference with ABCG2
activity due to genetic, pathological or iatrogenic factors would increase the
amount of AZT reaching the fetal brain, which could increase the risk of toxicity
of this drug on the tissue.
PMID- 28705595
TI - Excretory/secretory antigens of Strongyloides venezuelensis applied to IgG
detection in human strongyloidosis.
AB - Strongyloidosis is a neglected disease that affects millions of people around the
world. The cases that particularly deserve attention are those related to
hyperinfection, mainly in immunocompromised patients. In this sense, there is a
need to improve the serological diagnosis of this helminth. The objective of this
study was therefore to produce and characterize excretory/secretory (E/S)
antigens of Strongyloides venezuelensis infective larvae (L3) for use as a
heterologous antigen in the diagnosis of human strongyloidosis and other
parasitic infection groups. Soluble antigenic preparations were produced as total
saline extract (SE), E/S in Roswell Park Memorial Institute 1640 (RPMI) and E/S
in phosphate buffered saline (PBS). The three antigenic preparations showed
similar protein bands. An ELISA showed that the E/S antigens were profitable,
easy to use, and more sensitive and specific than SE, eliminating cross
reactivity with other parasites in serum samples. The detection of anti
Strongyloides stercoralis in the sera of patients with strongyloidosis and those
with immunosuppressive conditions using S. venezuelensis L3 larvae E/S antigens
was satisfactory. RPMI and PBS E/S antigens were also superior in terms of
specificity than SE.
PMID- 28705596
TI - Isolation and characterization of aerobic anoxygenic phototrophs from exposed
soils from the Sor Rondane Mountains, East Antarctica.
AB - This study investigated the culturable aerobic phototrophic bacteria present in
soil samples collected in the proximity of the Belgian Princess Elisabeth Station
in the Sor Rondane Mountains, East Antarctica. Until recently, only oxygenic
phototrophic bacteria (Cyanobacteria) were well known from Antarctic soils.
However, more recent non-cultivation-based studies have demonstrated the presence
of anoxygenic phototrophs and, particularly, aerobic anoxygenic phototrophic
bacteria in these areas. Approximately 1000 isolates obtained after prolonged
incubation under different growth conditions were studied and characterized by
matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.
Representative strains were identified by sequence analysis of 16S rRNA genes.
More than half of the isolates grouped among known aerobic anoxygenic
phototrophic taxa, particularly with Sphingomonadaceae, Methylobacterium and
Brevundimonas. In addition, a total of 330 isolates were tested for the presence
of key phototrophy genes. While rhodopsin genes were not detected, multiple
isolates possessed key genes of the bacteriochlorophyll synthesis pathway. The
majority of these potential aerobic anoxygenic phototrophic strains grouped with
Alphaproteobacteria (Sphingomonas, Methylobacterium, Brevundimonas and
Polymorphobacter).
PMID- 28705597
TI - [Systemic sclerosis and occupational difficulties: Results of a prospective
study].
AB - Between 9000 and 14000 people have systemic sclerosis (ScS) in France. The work
is often affected. Our study aims to assess the frequency of professional
difficulties (DP) of scleroderma patients, identify these DP, the symptoms
involved and the solutions used. A heteroquestionnaire was offered to scleroderma
patients the Lille University Hospital. Data were cross-checked with the clinical
database of the National Observatory of scleroderma patients. We used 104
questionnaires of which 84% are women. A total of 62.5%, (95% CI [52.5 to 71.8])
patients had experienced DP related to SSc, 55% reported symptoms worsened at
work, 41% lower efficiency and a 19% job loss. Symptoms responsible for their DP
were mainly asthenia, Raynaud syndrome, arthralgias and finger ulcerations. Only
40% of patients in difficulty were initiating steps with the county home for
disabled people and 45% in informing their doctor at work (MT). The MT
information absence was related to a misunderstanding of possible aid in 45% of
cases, 57% of patients had not found a solution, 41% of them have lost their jobs
and 31% of patients in the cohort experienced a drop in income. The impact of SSc
the work is important. The aid job retention devices are under-used due to lack
of knowledge of steps to take and the role of MT. Taking into account the
symptoms responsible for PD must be improved to participate in this retention.
PMID- 28705598
TI - Right internal thoracic artery or saphenous vein grafting? Insanity: Doing the
same thing over and over again and expecting different results.
PMID- 28705599
TI - Psychosis relapse, medication non-adherence, and cannabis.
PMID- 28705600
TI - Poor medication adherence and risk of relapse associated with continued cannabis
use in patients with first-episode psychosis: a prospective analysis.
AB - BACKGROUND: Cannabis use following the onset of first-episode psychosis has been
linked to both increased risk of relapse and non-adherence with antipsychotic
medication. Whether poor outcome associated with cannabis use is mediated through
an adverse effect of cannabis on medication adherence is unclear. METHODS: In a
prospective analysis of data acquired from four different adult inpatient and
outpatient units of the South London and Maudsley Mental Health National Health
Service Foundation Trust in London, UK, 245 patients were followed up for 2 years
from the onset of first-episode psychosis. Cannabis use after onset of psychosis
was assessed by self-reports in face-to-face follow-up interviews. Relapse data
were collected from clinical notes using the WHO Life Chart Schedule. This
measure was also used to assess medication adherence on the basis of both face-to
face interviews and clinical notes. Patients were included if they had a
diagnosis of first-episode non-organic or affective psychosis according to ICD-10
criteria, and were aged between 18 and 65 years when referred to local
psychiatric services. We used structural equation modelling analysis to estimate
whether medication adherence partly mediated the effects of continued cannabis
use on risk of relapse. The primary outcome variable was relapse, defined as
admission to a psychiatric inpatient unit after exacerbation of symptoms within 2
years of first presentation to psychiatric services. Information on cannabis use
over the first 2 years after onset of psychosis was investigated as a predictor
variable for relapse. Medication adherence was assessed as a mediator variable on
the basis of clinical records and self-report data. Study researchers (TS, NP,
EK, and EF) rated the adherence. FINDINGS: 397 patients who presented with their
first episode of psychosis between April 12, 2002, and July 26, 2013 had a follow
up assessment until September, 2015. Of the 397 patients approached for followed
up, 133 refused to take part in this study and 19 could not be included because
of missing data. 91 (37%) of 245 patients with first-episode psychosis had a
relapse over the 2 years of follow-up. Continued cannabis use predicted poor
outcome, including risk of relapse, number of relapses, length of relapse, and
care intensity at follow-up. In controlled structural equation modelling
analyses, medication adherence partly mediated the effect of continued cannabis
use on outcome, including risk of relapse (proportion mediated=26%, betaindirect
effects=0.08, 95% CI 0.004 to 0.16), number of relapses (36%, betaindirect
effects=0.07, 0.003 to 0.14), time until relapse (28%, betaindirect effects=
0.26, -0.53 to 0.001) and care intensity (20%, betaindirect effects=0.06, 0.004
to 0.11) but not length of relapse (6%, betaindirect effects=0.03, -0.03 to
0.09). The adjusted models explained moderate amounts of variance for outcomes
defined as risk of relapse (R2=0.25), number of relapses (R2=0.21), length of
relapse (R2=0.07), time until relapse (R2=0.08), and care intensity index
(R2=0.15). INTERPRETATION: Between 20% and 36% of the adverse effects of
continued cannabis use on outcome in psychosis might be mediated through the
effects of cannabis use on medication adherence. Interventions directed at
medication adherence could partly help mitigate the harm from cannabis use in
psychosis. FUNDING: This study is funded by the National Institute of Health
Research (NIHR) Clinician Scientist award.
PMID- 28705601
TI - Cannabis use, attitudes, and legal status in the U.S.: A review.
AB - Cannabis is widely used among adolescents and adults. In the U.S., marijuana laws
have been changing, and Americans increasingly favor legalizing cannabis for
medical and recreational uses. While some can use cannabis without harm, others
experience adverse consequences. The objective of this review is to summarize
information on the legal status of cannabis, perceptions regarding cannabis,
prevalence and time trends in use and related adverse consequences, and evidence
on the relationship of state medical (MML) and recreational (RML) marijuana laws
to use and attitudes. Twenty-nine states now have MMLs, and eight of these have
RMLs. Since the early 2000s, adult and adolescent perception of cannabis use as
risky has decreased. Over the same time, the prevalence of adolescent cannabis
use has changed little. However, adult cannabis use, disorders, and related
consequences have increased. Multiple nationally representative studies indicate
that MMLs have had little effect on cannabis use among adolescents. However,
while MML effects have been less studied in adults, available evidence suggests
that MMLs increase use and cannabis use disorders in adults. While data are not
yet available to evaluate the effect of RMLs, they are likely to lower price,
increase availability, and thereby increase cannabis use. More permissive
marijuana laws may accomplish social justice aims (e.g., reduce racial
disparities in law enforcement) and generate tax revenues. However, such laws may
increase cannabis-related adverse health and psychosocial consequences by
increasing the population of users. Dissemination of balanced information about
the potential health harms of cannabis use is needed.
PMID- 28705602
TI - Juvenile psammomatoid ossifying fibromas of the ethmoid: Natural history in
adults.
PMID- 28705603
TI - Ischemic heart disease in children and young adults with congenital heart disease
in Sweden.
AB - BACKGROUND: An increasing proportion of congenital heart disease (CoHD) patients
survive to an age associated with increased risk of developing ischemic heart
disease (IHD). The aim was to investigate the risk of developing IHD among
children and young adults with CoHD. METHODS: Using the Swedish National Patient
Register, we created a cohort of all CoHD patients born between January 1970 and
December 1993. Ten controls matched for age, sex, county were randomly selected
from the general population for each patient (n=219,816). Patients and controls
were followed from birth until first IHD event, death, or December 31, 2011.
RESULTS: We identified 21,982 patients with CoHD (51.6% men), mean follow-up was
26.4 (21.2-33.9) years. CoHD patients had 16.5 times higher risk of being
hospitalized with or dying from IHD compared to controls (95% CI: 13.7-19.9),
p<0.0001. Patients with conotruncal defects and severe nonconotruncal defects,
had the highest IHD incidence rate (71.1 and 56.3 cases per 100,000 person-years,
respectively, compared to 2.9 and 2.3 in controls). Hypertension and diabetes
were less common among CoHD patients with IHD than among controls with IHD
(hypertension 9.7% vs 19.7%, diabetes 1.8% vs 7.7% in CoHD patients and
controls). Patients with aortic coarctation did not have a specific increase in
the risk of developing IHD or acute myocardial infarction. CONCLUSIONS: In this
large case-control cohort study, the relative risk of developing IHD was markedly
higher in CoHD patients than in controls. However, the absolute risk was low in
both groups.
PMID- 28705604
TI - Major depression and heart failure: Interest of monoamine oxidase inhibitors.
AB - Several physiopathological hypotheses have been studied to explain the link
between heart failure (HF) and major depression (MD). An increase of monoamine
oxidase (MAO) has recently been found as a factor involved in the development of
HF. The aim of this review is to provide a complete overview of the involvement
of MAOs in HF comorbidity of MD and to discuss the pharmacological options. Our
work highlights the scientific evidence of MAO involvement in the development of
HF. Studies focusing on MAO-A seem to have reproducible results on HF,
establishing the effect of this enzyme as well as the protective effect of its
inhibition. Fewer studies addressed MAO-B; results are nonetheless encouraging.
Based on this knowledge, the hypothesis of a rise of MAO activity in HF seems to
be well established. The large prevalence of comorbid MD in HF could be due to
the deamination of monoamines linked with MAOs activity. In addition, MAOIs are
effective in MD and well tolerated among the elderly according to the literature.
This original hypothesis provides a new perspective in the use of MAOIs in HF
patients with MD.
PMID- 28705605
TI - Age of menarche is associated with knee joint replacement due to primary
osteoarthritis (The HUNT Study and the Norwegian Arthroplasty Register).
AB - OBJECTIVE: To investigate whether parity, age at menarche, menopausal status, age
at menopause, use of oral contraceptives (OC) or use of hormone replacement
therapy (HRT) were associated with total knee replacement (TKR) or total hip
replacement (THR) due to primary osteoarthritis. METHOD: In a prospective cohort
study of 30,289 women from the second and third surveys of the Nord-Trondelag
Health Study, data were linked to the Norwegian Arthroplasty Register (NAR) in
order to identify TKR or THR due to primary osteoarthritis. Cox proportional
hazards models were used to estimate the hazard ratios (HRs). RESULTS: We
observed 430 TKRs and 675 THRs during a mean follow-up time of 8.3 years.
Increasing age at menarche was inversely associated with the risk of TKR (P-trend
< 0.001). Past users and users of systemic HRT were at higher risk of TKR
compared to never users (HR 1.42 (95% confidence interval (CI) 1.06-1.90) and HR
1.40 (95% CI 1.03-1.90), respectively). No association was found between parity,
age at menarche, menopausal status, age at menopause, oral contraceptive use or
HRT use and THR. CONCLUSION: We found that increasing age at menarche reduced the
risk of TKR. Past users and users of systemic HRT were at higher risk of TKR
compared to never users. Parity did not increase the risk of THR or TKR.
PMID- 28705606
TI - Regenerative approaches for cartilage repair in the treatment of osteoarthritis.
AB - Osteoarthritis (OA) as a debilitating affliction of joints currently affects
millions of people and remains an unsolved problem. The disease involves multiple
cellular and molecular pathways that converge on the progressive destruction of
cartilage. Activation of cartilage regenerative potential and specific targeting
pathogenic mediators have been the major focus of research efforts aimed at
slowing the progression of cartilage degeneration and preserve joint function.
This review will summarize recent key discoveries toward better understanding of
the complex mechanisms behind OA development and highlight the latest advances in
basic and clinical research in the approach for cartilage regeneration.
Prospectively, more potent therapeutic strategies against progressive cartilage
deterioration may use a combination of cytotherapy, pharmacotherapy, and
bioscaffoldings for improved chondrogenic differentiation and stem/progenitor
cell homing as well as the concomitant reduced enzymatic matrix degradation and
inflammation. Further, treatments need to be provided with increased preciseness
of targeted therapy. One might expect that the regenerative therapies could
potentially control or even possibly cure OA if performed at early stages of the
disease.
PMID- 28705607
TI - Noise-induced hearing loss induces loudness intolerance in a rat Active Sound
Avoidance Paradigm (ASAP).
AB - Hyperacusis is a loudness hypersensitivity disorder in which moderate-intensity
sounds are perceived as extremely loud, aversive and/or painful. To assess the
aversive nature of sounds, we developed an Active Sound Avoidance Paradigm (ASAP)
in which rats altered their place preference in a Light/Dark shuttle box in
response to sound. When no sound (NS) was present, rats spent more than 95% of
the time in the Dark Box versus the transparent Light Box. However, when a 60 or
90 dB SPL noise (2-20 kHz, 2-8 kHz, or 16-20 kHz bandwidth) was presented in the
Dark Box, the rats'' preference for the Dark Box significantly decreased. Percent
time in the dark decreased as sound intensity in the Dark Box increased from 60
dB to 90 dB SPL. Interestingly, the magnitude of the decrease was not a monotonic
function of intensity for the 16-20 kHz noise and not related to the bandwidth of
the 2-20 kHz and 2-8 kHz noise bands, suggesting that sound avoidance is not
solely dependent on loudness but the aversive quality of the noise as well.
Afterwards, we exposed the rats for 28 days to a 16-20 kHz noise at 102 dB SPL;
this exposure produced a 30-40 dB permanent threshold shift at 16 and 32 kHz.
Following the noise exposure, the rats were then retested on the ASAP paradigm.
High-frequency hearing loss did not alter Dark Box preference in the no-sound
condition. However, when the 2-20 kHz or 2-8 kHz noise was presented at 60 or 90
dB SPL, the rats avoided the Dark Box significantly more than they did before the
exposure, indicating these two noise bands with energy below the region of
hearing loss were perceived as more aversive. In contrast, when the 16-20 kHz
noise was presented at 60 or 90 dB SPL, the rats remained in the Dark Box
presumably because the high-frequency hearing loss made 16-20 kHz noise less
audible and less aversive. These results indicate that when rats develop a high
frequency hearing loss, they become less tolerant of low frequency noise, i.e.,
high intensity sounds are perceived as more aversive and should be avoided.
PMID- 28705608
TI - The impact of hearing aids and age-related hearing loss on auditory plasticity
across three months - An electrical neuroimaging study.
AB - The present study investigates behavioral and electrophysiological auditory and
cognitive-related plasticity in three groups of healthy older adults (60-77
years). Group 1 was moderately hearing-impaired, experienced hearing aid users,
and fitted with new hearing aids using non-linear frequency compression (NLFC
on); Group 2, also moderately hearing-impaired, used the same type of hearing
aids but NLFC was switched off during the entire period of study duration (NLFC
off); Group 3 represented individuals with age-appropriate hearing (NHO) as
controls, who were not different in IQ, gender, or age from Group 1 and 2. At
five measurement time points (M1-M5) across three months, a series of active
oddball tasks were administered while EEG was recorded. The stimuli comprised
syllables consisting of naturally high-pitched fricatives (/sh/, /s/, and /f/),
which are hard to distinguish for individuals with presbycusis. By applying a
data-driven microstate approach to obtain global field power (GFP) as a measure
of processing effort, the modulations of perceptual (P50, N1, P2) and cognitive
related (N2b, P3b) auditory evoked potentials were calculated and subsequently
related to behavioral changes (accuracy and reaction time) across time. All
groups improved their performance across time, but NHO showed consistently higher
accuracy and faster reaction times than the hearing-impaired groups, especially
under difficult conditions. Electrophysiological results complemented this
finding by demonstrating longer latencies in the P50 and the N1 peak in hearing
aid users. Furthermore, the GFP of cognitive-related evoked potentials decreased
from M1 to M2 in the NHO group, while a comparable decrease in the hearing
impaired group was only evident at M5. After twelve weeks of hearing aid use of
eight hours each day, we found a significantly lower GFP in the P3b of the group
with NLFC on as compared to the group with NLFC off. These findings suggest
higher processing effort, as evidenced by higher GFP, in hearing-impaired
individuals when compared to those with normal hearing, although the hearing
impaired show a decrease of processing effort after repeated stimulus exposure.
In addition, our findings indicate that the acclimatization to a new hearing aid
algorithm may take several weeks.
PMID- 28705609
TI - Hand, shoulder and back stiffness in long-term type 1 diabetes; cross-sectional
association with skin collagen advanced glycation end-products. The Dialong
study.
AB - AIMS: We aimed to: (i) estimate the prevalence of Dupuytren's disease, trigger
finger, carpal tunnel syndrome and frozen shoulder; (ii) assess stiffness of the
hand, shoulder and back; and (iii) explore the association of joint stiffness
with both long-term HbA1c and collagen advanced glycation end-products (AGEs) in
long-term type 1 diabetes mellitus (T1DM). METHODS: Patients with T1DM from 1970
or earlier attending a specialized diabetes center were included in this cross
sectional controlled study. We collected HbA1/HbA1c measurements from 1980 to
2015 and data on hand and shoulder diagnoses and joint stiffness through
interviews, charts, and standardized examination. Skin biopsies were analyzed for
collagen AGEs by liquid chromatography-mass spectrometry. RESULTS: Lifetime
prevalence of hand and shoulder diagnoses in the diabetes group (n=102) ranged
from 37%-76% (frozen shoulder) versus 11%-15% in controls (n=73) (p<0.001). There
was an association between joint stiffness and long-term HbA1c (odds ratio 2.01
[95% CI 1.10-3.7]) and the AGEs methyl-glyoxal-lysine-dimer (odds ratio 1.68 [95%
CI 1.03-2.73]) and pentosidine (odds ratio 1.81 [95% CI 1.04-3.16]). CONCLUSIONS:
Patients with T1DM >45years had a very high prevalence of hand and shoulder
diagnoses versus controls. Joint stiffness was associated with collagen AGEs.
However, joint biopsies and prospective studies must explore this association
further.
PMID- 28705610
TI - Breeding protocol for the sand fly Nyssomyia neivai (Diptera: Psychodidae) in
laboratory conditions.
AB - The information in this protocol covers from the basic steps and material
necessary to start a sand fly colony up to the specific details which are
important to the success of a Nyssomyia neivai colony. The greatest problems in
our colony of Ny. neivai were solved with specific care, for instance, using
vermiculite and an adequate number of adults in oviposition containers; the
control of fungus with the exact amount of diet for the larvae and humidity
control; a second blood meal for females and control of the number of times
animals are used for blood meals. Currently, our colony is at F22 generation.
PMID- 28705611
TI - Field evaluation of a new light trap for phlebotomine sand flies.
AB - Light traps are one of the most common attractive method for the collection of
nocturnal insects. Although light traps are generally referred to as "CDC light
traps", different models, equipped with incandescent or UV lamps, have been
developed. A new light trap, named Laika trap 3.0, equipped with LED lamps and
featured with a light and handy design, has been recently proposed into the
market. In this study we tested and compared the capture performances of this new
trap with those of a classical light trap model under field conditions. From May
to November 2013, a Laika trap and a classical light trap were placed biweekly in
an area endemic for sand flies. A total of 256 sand fly specimens, belonging to 3
species (Sergentomyia minuta, Phlebotomus perniciosus, Phlebotomus neglectus)
were collected during the study period. The Laika trap captured 126 phlebotomine
sand flies: P. perniciosus (n=38); S. minuta (n=88), a similar number of
specimens (130) and the same species were captured by classical light trap which
collected also 3 specimens of P. neglectus. No significant differences in the
capture efficiency at each day of trapping, neither in the number of species or
in the sex of sand flies were observed. According to results of this study, the
Laika trap may be a valid alternative to classical light trap models especially
when handy design and low power consumption are key factors in field studies.
PMID- 28705612
TI - Cardiac mitochondrial dynamics: miR-mediated regulation during cardiac injury.
AB - Mitochondrial integrity is indispensable for cardiac health. With the advent of
modern imaging technologies, mitochondrial motility and dynamics within the cell
are extensively studied. Terminally differentiated and well-structured
cardiomyocytes depict little mitochondrial division and fusion, questioning the
contribution of mitochondrial fusion proteins (Mitofusin 1/2 and Optic Atrophy 1
protein) and fission factors (Dynamin-like protein 1 and mitochondrial fission 1
protein) in cardiomyocyte homeostasis. Emerging evidences suggest that
alterations in mitochondrial morphology from globular, elongated network to
punctate fragmented disconnected structures are a pathological response to
ensuing cardiac stress and cardiomyocyte cell death, bringing forth the following
question, "what maintains this balance between fusion and fission?" The answer
hinges upon the classical "junk" DNA: microRNAs, the endogenous non-coding RNAs.
Because of their essential role in numerous signaling pathways, microRNAs are
considered to play major roles in the pathogenesis of various diseases.
Mitochondria are not exempted from microRNA-mediated regulation. This review
defines the importance of mitochondrial structural integrity and the microRNA
mitochondrial dynamics tandem, an imminent dimension of the cardiac homeostasis
network. Elucidating their coordinated interaction could spur RNA-based
therapeutics for resuscitating functional mitochondrial population during
cardiovascular disorders.
PMID- 28705613
TI - Aging-related effects of bed rest followed by eccentric exercise rehabilitation
on skeletal muscle macrophages and insulin sensitivity.
AB - The pro- and anti-inflammatory macrophages are associated with insulin
sensitivity and skeletal muscle regeneration. Infiltrating macrophages in
skeletal muscle during a period of physical inactivity and subsequent
reloading/rehabilitation in older adults is unknown, but may provide insight into
mechanisms related to the development of metabolic disease and changes in muscle
cell size. The purpose of this study was to determine if skeletal muscle
macrophage infiltration is modulated differently between young and older adults
after bed rest and exercise rehabilitation and if these responses are related to
muscle and insulin sensitivity changes. 14 young and 9 older adults underwent 5
days of bed rest followed by 8-weeks of lower limb eccentric exercise
rehabilitation (REHAB). Dual-energy X-ray absorptiometry, magnetic resonance
imaging and myofiber analysis were used to identify muscle morphology and CLIX-IR
and CLIX-beta were used to assess insulin sensitivity. Skeletal muscle
macrophages, CD68 (pan), CD11b (M1), CD163 (M2), CD206 (M2), were characterized
using immunohistochemistry and gene expression. Insulin sensitivity, independent
of age, decreased ~38% following bed rest and was restored following REHAB. We
found robust age-related differences in muscle atrophy during bed rest, yet older
and younger adults equally hypertrophied during REHAB. Interestingly, there were
age-related differences in macrophage content (CD68+CD11b+ and CD68+CD11b- cells)
but both young and old similarly increased macrophages with REHAB. Satellite cell
changes during rehab corresponded to macrophage content changes. Muscle tissue
resident macrophages and gene expression, were not associated with changes in
insulin sensitivity following bed rest and REHAB. These data suggest that muscle
macrophages are modulated as a result of exercise rehabilitation following bed
rest and may more associated with muscle regrowth/hypertrophy rather than insulin
sensitivity in young or older adults. This trial was registered at
clinicaltrials.gov as NCT01669590.
PMID- 28705614
TI - Tracing molecular and structural changes upon mucolysis with N-acetyl cysteine in
human airway mucus.
AB - The conducting airways of the human lungs are lined by mucus, which lubricates
the lung epithelium and provides a first-line protection against airborne
threats. As a novel approach for visualization of the human mucus microstructure,
we applied confocal Raman microscopy as a label-free and chemically selective
technique. We were successfully able to chemically resolve the pulmonary
surfactant from the mucus matrix and show its spatial distribution, as well as to
visualize the structural changes within the freeze-dried mucus mesh upon chemical
mucolysis. Subsequently, we performed rheological measurements before and after
mucolysis and correlated morphology and chemical structure of the mucus with its
rheological characteristics. These results do not only enrich the knowledge about
the mucus microstructure, but can also, significantly contribute to rational
development of future lung therapeutics.
PMID- 28705615
TI - Transcutaneous immunotherapy of pollinosis using solid-in-oil nanodispersions
loaded with T cell epitope peptides.
AB - Pollinosis, a typical seasonal allergy, is a serious public health problem.
Limited numbers of patients receive curative immunotherapy instead of symptomatic
therapy; however, there are still some concerns about the inconvenience and side
effects of subcutaneous injections and sublingual administration caused by
immunotherapy. Here, we propose a simple and safe transcutaneous immunotherapy
using solid-in-oil (S/O) nanodispersions loaded with vaccine T cell epitope
peptides derived from pollen allergen. S/O nanodispersions are oil-based
dispersions of antigens coated with hydrophobic surfactants. They have a high
potential to deliver biomolecules including peptides or proteins to immune cells
in the skin, and to induce an immune response. The result of quantitative and
qualitative analysis by in vitro permeation experiments demonstrated the
effective permeation of T cell epitope peptides into the skin. Furthermore, in
vivo experiments using a pollinosis mouse model indicated that the S/O
nanodispersions loaded with T cell epitopes suppressed serum antibody IgE and
cytokine production, and alleviated allergic symptoms to a similar therapeutic
level to that observed for subcutaneous injection. These results indicate the
potential of transcutaneous immunotherapy using S/O nanodispersions for the
future treatment of pollinosis.
PMID- 28705616
TI - Improvement of the surface hydrophilic properties of naproxen particles with
addition of hydroxypropylmethyl cellulose and sodium dodecyl sulphate: In vitro
and in vivo studies.
AB - In this study, a new surface-modified naproxen was developed to enhance brain
concentration in acute migraine treatment. Fast-dissolving naproxen granules were
made by mixing hydroxypropylmethylcellulose (HPMC) sodium dodecyl sulphate (SDS)
and sodium croscarmellose with micronized naproxen particles. The aim of this
study was to evaluate the effect of adding proportions of SDS to the HPMC film
caused changes in the polymer chains of the HPMC, producing a new hydrophilic
HPMC-SDS structure. These formulations with different HPMC/SDS ratios were
characterised using electron microscopy (SEM), powder X-ray diffraction (PXRD),
and differential scanning calorimetry (DSC). SDS 10% (w/w) produced a highly
hydrophilic HPMC-SDS structure on the surface of the naproxen microparticles. The
fast dissolution granules (SF-10%) showed a significant improvement in the
dissolution rate of naproxen. Pharmacokinetic studies were conducted with mice,
showing an improvement of Cmax (1.38 and 1.41-fold) and AUC0-2h (30% and 10%
higher) for plasma and brain samples compared to the reference naproxen
suspension. The faster Tmax ratio for SF-10% may be related to increased
hydration in the gastrointestinal environment, enabling the drug to permeate the
gastrointestinal hydration layer more easily due to the presence of the
hydrophilic HPMC-SDS structure in the formulation.
PMID- 28705617
TI - Drug solubility in lipid nanocarriers: Influence of lipid matrix and available
interfacial area.
AB - Amongst other strategies for the formulation of poorly water-soluble drugs,
solubilization of these drugs in lipid-based formulations is a promising option.
Most screening methods for the identification of a suitable lipid-based
formulation fail to elucidate the role interfacial effects play for drug
solubility in disperse systems. In a novel screening approach called passive drug
loading, different preformed lipid nanocarrier dispersions are incubated with
drug powder. Afterwards, undissolved drug is filtered off and the amount of
solubilized drug is determined. The aim of this study was to identify parameters
for drug solubility in pure lipids as well as for drug loading to the lipid-water
interface of lipid nanoparticles. Using passive loading, the solubility of eight
poorly water-soluble drugs in seven lipid nanocarriers varying in particle size
or lipid matrix was investigated. Drug solubility in the nanocarriers did not
follow any apparent trend and different drugs dissolved best in different
carriers. Drugs with a melting point below approximately 150 degrees C displayed
distinctly better solubility than higher melting drugs. Additionally, relating
the specific lipid nanocarrier surface area to the drug solubility allowed
drawing conclusions on the drug localization. Fenofibrate, dibucaine and, less
distinctly also clotrimazole, which all melt below 150 degrees C, were
predominantly located in the lipid droplet core of the nanoparticles. In
contrast, the five remaining drugs (betamethasone valerate, flufenamic acid,
itraconazole, ketoconazole, mefenamic acid) were also located at the lipid-water
interface to different, but substantial degrees. The ability to account for drug
loading to the lipid-water interface is thus a major advantage of passive
loading.
PMID- 28705618
TI - The impact of guest compounds on cyclodextrin aggregation behavior: A series of
structurally related parabens.
AB - Several studies have demonstrated the presence of aggregates in aqueous
cyclodextrin containing solutions. The presence of guest compounds has been shown
to influence this cyclodextrin aggregation process. In an attempt to gain insight
into the effect of the physicochemical properties of the guest compound on 2
hydroxypropyl-beta-cyclodextrin aggregation formation, a series of structurally
related parabens was selected as model compounds. Using nuclear magnetic
resonance spectroscopy and phase solubility studies, these parabens, differing
only in side chain length, were demonstrated to form inclusion complexes with 2
hydroxypropyl-beta-cyclodextrin. Additional techniques were subsequently applied
to evaluate the aggregation behavior of this cyclodextrin in presence of the
selected parabens. Solutions containing a broad range of 2-hydroxypropyl-beta
cyclodextrin concentrations were saturated with the guest compounds and were used
as test media. Results obtained from dialysis experiments, dynamic light
scattering and mass spectrometry revealed a positive effect of the side chain
length of the parabens on aggregate formation: in presence of heptylparaben, more
and larger aggregates were observed than in presence of parabens with shorter
side chains such as methyl- and butylparaben. No clear connection could be
demonstrated between the cyclodextrin concentration and the extent of aggregate
formation in presence of the guest compound.
PMID- 28705619
TI - Patient acceptability, safety and access: A balancing act for selecting age
appropriate oral dosage forms for paediatric and geriatric populations.
AB - The selection and design of age-appropriate formulations intended for use in
paediatric and geriatric patients are dependent on multiple factors affecting
patient acceptability, safety and access. The development of an economic and
effective product relies on a balanced consideration of the risks and benefits of
these factors. This review provides a comprehensive and up-to-date analysis of
oral dosage forms considering key aspects of formulation design including dosage
considerations, ease of use, tolerability and safety, manufacturing complexity,
stability, supply and cost. Patient acceptability has been examined utilising an
evidence-based approach to evaluate regulatory guidance and literature. Safety
considerations including excipients and potential risk of administration errors
of the different dosage forms are also discussed, together with possible
manufacturing and supply challenges. Age appropriate drug product design should
consider and compare i) acceptability ii) safety and iii) access, although it is
important to recognise that these factors must be balanced against each other,
and in some situations a compromise may need to be reached when selecting an age
appropriate formulation.
PMID- 28705620
TI - Application of continuous twin screw granulation for the metformin hydrochloride
extended release formulation.
AB - This study focuses on evaluating the potential of transferring from a batch
process to continuous process for manufacturing of the extended release
formulation. Metformin hydrochloride (HCl) was used in the model formulation
which was intended to contain the high amount of hydrophilic drug. The effects of
barrel temperature, binder type, powder feed rate, and screw speed on granule
properties (size and strength) and torque value in twin screw granulation were
investigated. Due to the high content of hydrophilic model drug, the granules
prepared at a higher temperature with HPMC binding solution had the narrower size
distribution and greater strength than the granules prepared with distilled water
as a binding solution. After continuous drying and milling steps, the granules
(continuous process) satisfied the fundamental purpose of granulation with size
and flowability, despite different shape compared with the granules (batch
process). Furthermore, there were no significant differences between two
granulation processes in tablet properties, such as tablet hardness and in vitro
release. The considerations and strategies used in this study to transfer from a
batch to continuous process can be applied to other existing formulations based
on high shear granulation to enable rapid process transfer in the pharmaceutical
industry.
PMID- 28705621
TI - Functionalized PLA-PEG nanoparticles targeting intestinal transporter PepT1 for
oral delivery of acyclovir.
AB - Targeting intestinal di- and tri-peptide transporter PepT1 with prodrugs is a
successful strategy to improve oral drug bioavailability, as demonstrated with
valacyclovir, a prodrug of acyclovir. The aim of this new drug delivery strategy
is to over-concentrate a poorly absorbed drug on the intestinal membrane surface
by targeting PepT1 with functionalized polymer nanoparticles. In the present
study, poly(lactic acid)-poly(ethylene glycol)-ligand (PLA-PEG-ligand)
nanoparticles were obtained by nanoprecipitation. A factorial experimental design
allowed us to identify size-influent parameters and to obtain optimized ~30nm
nanoparticles. Valine, Glycylsarcosine, Valine-Glycine, and Tyrosine-Valine were
chemically linked to PLA-PEG. In Caco-2 cell monolayer model, competition between
functionalized nanoparticles and [3H]Glycylsarcosine, a strong substrate of
PepT1, reduced [3H]Glycylsarcosine transport from 22 to 46%. Acyclovir was
encapsulated with a drug load of ~10% in valine-functionalized nanoparticles,
resulting in a 2.7-fold increase in permeability as compared to the free drug. An
in vivo pharmacokinetic study in mice compared oral absorption of acyclovir after
administration of 25mg/kg of valacyclovir, free or encapsulated acyclovir in
functionalized nanoparticles. Acyclovir encapsulation did not statistically
modify AUC or Cmax, but increased t1/2 and MRT 1.3-fold as compared to free
acyclovir. This new strategy is promising for poorly absorbed drugs by oral
administration.
PMID- 28705622
TI - Long-term toxicological effects of persistent luminescence nanoparticles after
intravenous injection in mice.
AB - The ZnGa1.995Cr0.005O4 persistent luminescence nanoparticles offer the promise of
revolutionary tools for biological imaging with applications such as cell
tracking or tumor detection. They can be re-excited through living tissues by
visible photons, allowing observations without any time constraints and avoiding
the undesirable auto-fluorescence signals observed when fluorescent probes are
used. Despite all these advantages, their uses demand extensive toxicological
evaluation and control. With this purpose, mice were injected with a single
intravenous administration of hydroxylated or PEGylated persistent luminescence
nanoparticles at different concentrations and then a set of standard tests were
carried out 1day, 1 month and 6 months after the administration. High
concentrations of hydroxylated nanoparticles generate structural alterations at
histology level, endoplasmic reticulum damage and oxidative stress in liver, as
well as rising in white blood cells counts. A mechanism involving the endoplasmic
reticulum damage could be the responsible of the observed injuries in case of ZGO
OH. On the contrary, no toxicological effects related to PEGylated nanoprobes
treatment were noted during our in vivo experiments, denoting the protective
effect of PEG-functionalization and thereby, their potential as biocompatible in
vivo diagnostic probes.
PMID- 28705623
TI - Water-induced phase separation of miconazole-poly (vinylpyrrolidone-co-vinyl
acetate) amorphous solid dispersions: Insights with confocal fluorescence
microscopy.
AB - The aim of this study was to evaluate the utility of confocal fluorescence
microscopy (CFM) to study the water-induced phase separation of miconazole-poly
(vinylpyrrolidone-co-vinyl acetate) (mico-PVPVA) amorphous solid dispersions
(ASDs), induced during preparation, upon storage at high relative humidity (RH)
and during dissolution. Different fluorescent dyes were added to drug-polymer
films and the location of the dyes was evaluated using CFM. Orthogonal
techniques, in particular atomic force microscopy (AFM) coupled with nanoscale
infrared spectroscopy (AFM-nanoIR), were used to provide additional analysis of
the drug-polymer blends. The initial miscibility of mico-PVPVA ASDs prepared
under low humidity conditions was confirmed by AFM-nanoIR. CFM enabled rapid
identification of drug-rich and polymer-rich phases in phase separated films
prepared under high humidity conditions. The identity of drug- and polymer-rich
domains was confirmed using AFM-nanoIR imaging and localized IR spectroscopy,
together with Lorentz contact resonance (LCR) measurements. The CFM technique was
then utilized successfully to further investigate phase separation in mico-PVPVA
films exposed to high RH storage and to visualize phase separation dynamics
following film immersion in buffer. CFM is thus a promising new approach to study
the phase behavior of ASDs, utilizing drug and polymer specific dyes to visualize
the evolution of heterogeneity in films exposed to water.
PMID- 28705624
TI - Evaluation of three-layered doxycycline-collagen loaded nanofiber wound dressing.
AB - Nanofiber wound dressings have great potential for both acute and chronic wound
healing. The aim of this study is to develop a wound dressing by the
electrospinning method and to determine its in vitro characteristics. The
viscosity and the surface tension values of the polymer solutions used in the
electrospinning were measured and their suitability for electrospinning was
evaluated. Nanofiber wound dressing consists of three layers. The first and the
second layers are sodium alginate and chitosan nanofibers, respectively. The core
of the coaxial nanofibers that comprises the third layer of the wound dressing
contains 1% polycaprolactone and 4.5% collagen, the shell comprises 2.5%
doxycycline and 2.5% polyethylene oxide. The developed wound dressing comprises
aligned nanofibers, with a contact angle of 38 degrees , a work of bioadhesion
value of 0.485mJ/cm2 on rat skin, a tensile strength of 2.76MPa, an elongation at
break value of 7.65%, a specific surface area of 9.65m2/g and a porosity of
52.3%. The amount of doxycycline content was found to be 260MUg/cm2 and the
complete drug release was achieved in 15min. No cytotoxic effect was shown in
cell culture studies with keratinocyte cell lines. As a result of the stability
studies, it was found that the morphological, mechanical, bioadhesion and
wettability properties and the amount of doxycycline remained stable for a period
of 12 months at 4 degrees C/ambient humidity condition. The developed three
layered wound dressing could be an alternative for wound healing applications.
PMID- 28705625
TI - Antiviral activity of gemcitabine against human rhinovirus in vitro and in vivo.
AB - Rhinovirus, a major causative agent of the common cold, is associated with
exacerbation of asthma and chronic obstructive pulmonary disease. Currently,
there is no antiviral treatment or vaccine for human rhinovirus (HRV).
Gemcitabine (2',2'-difluorodeoxycytidine, dFdC) is a deoxycytidine analog with
antiviral activity against rhinovirus, as well as enterovirus 71, in vitro.
However, the antiviral effects of gemcitabine in vivo have not been investigated.
In the current study, we assessed whether gemcitabine mediated antiviral effects
in the murine HRV infection model. Intranasal administration of gemcitabine
significantly lowered pulmonary viral load and inflammation by decreasing
proinflammatory cytokines, including TNF-alpha and IL-1beta, and reduction in the
number of lung-infiltrating lymphocytes. Interestingly, we found that the
addition of UTP and CTP significantly attenuated the antiviral activity of
gemcitabine. Thus the limitation of UTP and CTP by the addition of gemcitabine
may inhibit the viral RNA synthesis. These results suggest that gemcitabine, an
antineoplastic drug, can be repositioned as an antiviral drug to inhibit HRV
infection.
PMID- 28705626
TI - High-flow paediatric mandibular arteriovenous malformations: case reports and a
review of current management.
AB - High-flow vascular malformations in the paediatric population are potentially
life-threatening and are challenging to treat. This paper describes the
management of three cases of mandibular arteriovenous malformations and reviews
the contemporary management options for these serious lesions.
PMID- 28705627
TI - A new perspective of particle adsorption: Dispersed oil and granular materials
interactions in simulated coastal environment.
AB - This study, adsorption behaviors of dispersed oil in seawaters by granular
materials were explored in simulation environment. We quantitatively demonstrated
the dispersed oil adsorbed by granular materials were both dissolved petroleum
hydrocarbons (DPHs) and oil droplets. Furthermore, DPHs were accounted for 42.5%,
63.4%, and 85.2% (35.5% was emulsion adsorption) in the adsorption of dispersed
oil by coastal rocks, sediments, and bacterial strain particles respectively.
Effects of controlling parameters, such as temperature, particle size and
concentration on adsorption of petroleum hydrocarbons were described in detail.
Most strikingly, adsorption concentration was followed a decreasing order of
bacterial strain (0.5-2MUm)>sediments (0.005-0.625mm)>coastal rocks (0.2-1cm).
With particle concentration or temperature increased, adsorption concentration
increased for coastal rocks particle but decreased for sediments particle.
Besides, particle adsorption rate of petroleum hydrocarbons (n-alkanes and PAHs)
was different among granular materials during 60 days.
PMID- 28705628
TI - Characteristics and sources of anthropogenic and biogenic hydrocarbons in
sediments from the coast of Qatar.
AB - Surface sediment samples from the coastal zone of Qatar were collected and
analyzed to determine the characteristics, and sources of anthropogenic and
biogenic hydrocarbons. The main compounds in these surface sediments included n
alkanes, methyl n-alkanoates, diterpenoids, hopanes, steranes, phthalate esters,
polycyclic aromatic hydrocarbons (PAHs) and unresolved complex mixture (UCM).
Their total concentrations ranged from 18.7+/-3.7-81.1+/-7.5ng/g (3.7+/-0.6
10.4+/-4.8%) for n-alkanes, 8.3+/-2.3-51+/-3.4ng/g (3.0+/-2.0-5.6+/-2.0%) for
methyl n-alkanoates, 1.8+/-0.1-10.5+/-1.0ng/g (1.0+/-0.5-0.4+/-0.1%) for
diterpenoids, 0.0-79.3+/-7.4ng/g (0.0-7.9+/-0.6%) for hopanes, 0.0-32.9+/-7.9ng/g
(0.0-6.5+/-1.0%) for steranes, 0.7+/-0.1-36.3+/-3.4ng/g (0.1+/-0.1-1.9+/-3.4%)
for phthalates, 0.30+/-0.2-7.8+/-0.7ng/g (0.02+/-0.04-0.42+/-0.72%) for PAHs, and
38+/-9-609+/-57ng/g (38.5+/-13.4-56.5+/-13.4%) for UCM. The major sources of
these lipids were anthropogenic petroleum residues and plasticizers (80-89%),
with lesser amounts from natural higher plants and microbial residues (11-20%).
Petroleum residues and plasticizer inputs to the coastal sediments of Qatar
likely affect the marine ecosystems and associated species groups as well as
shallow coastal nursery and spawning areas.
PMID- 28705629
TI - Foraging preferences influence microplastic ingestion by six marine fish species
from the Texas Gulf Coast.
AB - This study evaluated the influence of foraging preferences on microplastic
ingestion by six marine fish species from the Texas Gulf Coast. A total of 1381
fish were analyzed and 42.4% contained ingested microplastic, inclusive of fiber
(86.4%), microbead (12.9% %), and fragment (<1.0%) forms. Despite a substantial
overlap in diet, ordination of ingested prey items clustered samples into
distinctive species groupings, reflective of the foraging gradient among species.
Orthopristis chrysoptera displayed the lowest overall frequency of microplastic
ingestion and the most distinctive ordination grouping, indicating their
selective invertebrate foraging preferences. Cluster analysis of O. chrysoptera
most closely classified microplastic with the ingestion of benthic invertebrates,
whereas the ingestion of microplastic by all other species most closely
classified with the ingestion of vegetation and shrimp. O. chrysoptera, as
selective invertebrate foragers, are less likely to ingest microplastics than
species exhibiting generalist foraging preferences and methods of prey capture.
PMID- 28705630
TI - Seasonal antioxidant responses in the sea urchin Paracentrotus lividus (Lamarck
1816) used as a bioindicator of the environmental contamination in the South-East
Mediterranean.
AB - In this study, sea urchin Paracentrotus lividus were sampled seasonally at three
stations during 2012 in the coastal areas of the Gulf of Annaba (southeast
Mediterranean). For all sea urchins, the gonad index was calculated to determine
sea urchin reproductive status. Moreover, a set of biochemical parameters,
including biomarkers and oxidative stress parameters, was measured in gonads. The
pesticides and physiochemical parameters were measured and dosed in sea water.
The results obtained highlighted that the levels of pesticide were generally low
and below those commonly applied by environmental quality standards (EQS),
indicating that no alarm state is currently present in the Gulf of Annaba. In
addition to pollution, seasonal change is an important factor influencing
biomarker activity, and the significant increases in biomarker levels in spring
are a major observed trend. This activity may also be related to reproductive
status. Seasonal variability was confirmed by the significant results of the
Kruskal-Wallis test and by the high degree of divergence between seasons in PCA,
with a total of 83.83% of variance explained. These results indicate that
environmental factors that vary seasonally may affect the antioxidant status of
the sea urchin Paracentrotus lividus.
PMID- 28705631
TI - Assessment and monitoring of water quality of the gulf of Morbihan, a littoral
ecosystem under high anthropic pressure.
AB - This field study is intended to propose a global methodology to assess and
monitor the water quality of the gulf of Morbihan, a littoral ecosystem under
increasing anthropic pressure. To this end, the Locmariaquer site, where
Crassostrea gigas is extensively cultivated, was selected to perform a one-year
follow-up of tissular glutathione S-transferase and acetylcholinesterase specific
activities in this filter feeder organism. Calculation of an integrated index,
corresponding to the ratio of the two enzymes activities, allowed to discriminate
from the environmental noise, several clusters which could be representative
environmental stress, potentially latent pollution. Moreover, the estrogenic
activity was assessed in water samples collected at Locmariaquer and other
strategic sites of the gulf. The results evidenced a low estrogenic-disrupting
compound contamination of waters. Overall, this methodology produced an accurate
outlook of a basal state for the gulf and could be developed in the context of a
chronic monitoring of this site.
PMID- 28705632
TI - The uptake of macroplastic & microplastic by demersal & pelagic fish in the
Northeast Atlantic around Scotland.
AB - This study reports plastic ingestion in various fish found from coastal and
offshore sites in Scottish marine waters. Coastal samples consisted of three
demersal flatfish species (n=128) collected from the East and West coasts of
Scotland. Offshore samples consisted of 5 pelagic species and 4 demersal species
(n=84) collected from the Northeast Atlantic. From the coastal fish sampled,
47.7% of the gastrointestinal tracts contained macroplastic and microplastic. Of
the 84 pelagic and demersal offshore fish, only 2 (2.4%) individuals from
different species had ingested plastic identified as a clear polystyrene fibre
and a black polyamide fibre. The average number of plastic items found per fish
from all locations that had ingested plastic was 1.8 (+/-1.7) with polyamide
(65.3%), polyethylene terephthalate (14.4%) and acrylic (14.4%) being the three
most commonly found plastics. This study adds to the existing data on
macroplastic and microplastic ingestion in fish species.
PMID- 28705633
TI - Transcriptome analysis of Helicoverpa armigera male hairpencils: Alcohol
biosynthesis and requirement for mating success.
AB - Many female animals use different strategies to assess male quality to increase
their own reproductive fitness. In moths, females usually use chemical signals
(sex pheromones) to attract males from a distance. Once males approach a female,
they release close range pheromones from hairpencils to facilitate female
acceptance. However, detailed mechanisms involved in male sex pheromone
biosynthesis and its action in promoting female acceptance have not yet been
fully characterized. This study screened a series of candidate genes via a
transcriptome analysis of the male hairpencil of Helicoverpa armigera. Using
pharmacological inhibitor and RNAi-mediated knockdown assays, we demonstrated
that Ca2+ and cyclic-AMP were involved in pheromone biosynthesis activating
neuropeptide (PBAN)-induced male sex pheromone biosynthesis. The functional
analysis of candidate enzymes involved in the male sex pheromone biosynthesis
pathway demonstrated that a decreased mRNA levels of acetyl-CoA carboxylase,
Delta11-desaturase, and fatty-acyl reductase 2 by RNAi-mediated knockdown led to
a significant decrease in the production of fatty acyl alcohols and the efficacy
of female acceptance. Our results demonstrated the important role of the fatty
acyl alcohol biosynthetic pathway in a PBAN-induced male sex pheromone
biosynthesis and the importance of hairpencil compounds in female mating
acceptance.
PMID- 28705634
TI - CRISPR/Cas9 mediated genome editing of Helicoverpa armigera with mutations of an
ABC transporter gene HaABCA2 confers resistance to Bacillus thuringiensis Cry2A
toxins.
AB - High levels of resistance to Bt toxin Cry2Ab have been identified to be
genetically linked with loss of function mutations of an ABC transporter gene
(ABCA2) in two lepidopteran insects, Helicoverpa armigera and Helicoverpa
punctigera. To further confirm the causal relationship between the ABCA2 gene
(HaABCA2) and Cry2Ab resistance in H. armigera, two HaABCA2 knockout strains were
created from the susceptible SCD strain with the CRISPR/Cas9 genome editing
system. One strain (SCD-A2KO1) is homozygous for a 2-bp deletion in exon 2 of
HaABCA2 created by non-homologous end joining (NHEJ). The other strain (SCD
A2KO2) is homozygous for a 5-bp deletion in exon 18 of HaABCA2 made by homology
directed repair (HDR), which was produced to mimic the r2 resistance allele of a
field-derived Cry2Ab-resistant strain from Australia. Both knockout strains
obtained high levels of resistance to both Cry2Aa (>120-fold) and Cry2Ab (>100
fold) compared with the original SCD strain, but no or very limited resistance to
Cry1Ac (<4-fold). Resistance to Cry2Ab in both knockouts is recessive, and
genetic complementary tests confirmed Cry2Ab resistance alleles are at the same
locus (i.e. HaABCA2) for the two strains. Brush border membrane vesicles (BBMVs)
of midguts from both knockout strains lost binding with Cry2Ab, but maintained
the same binding with Cry1Ac as the SCD strain. In vivo functional evidence from
this study demonstrates knockout of HaABCA2 confers high levels of resistance to
both Cry2Aa and Cry2Ab, confirming that HaABCA2 plays a key role in mediating
toxicity of both Cry2Aa and Cry2Ab against H. armigera.
PMID- 28705635
TI - Reply to "Antibiotic resistance: thinking outside the hospital".
PMID- 28705636
TI - A review of bioinformatics platforms for comparative genomics. Recent
developments of the EDGAR 2.0 platform and its utility for taxonomic and
phylogenetic studies.
AB - The rapid development of next generation sequencing technology has greatly
increased the amount of available microbial genomes. As a result of this
development, there is a rising demand for fast and automated approaches in
analyzing these genomes in a comparative way. Whole genome sequencing also bears
a huge potential for obtaining a higher resolution in phylogenetic and taxonomic
classification. During the last decade, several software tools and platforms have
been developed in the field of comparative genomics. In this manuscript, we
review the most commonly used platforms and approaches for ortholog group
analyses with a focus on their potential for phylogenetic and taxonomic research.
Furthermore, we describe the latest improvements of the EDGAR platform for
comparative genome analyses and present recent examples of its application for
the phylogenomic analysis of different taxa. Finally, we illustrate the role of
the EDGAR platform as part of the BiGi Center for Microbial Bioinformatics within
the German network on Bioinformatics Infrastructure (de.NBI).
PMID- 28705637
TI - [Do children with attention deficit and hyperactivity disorder (ADHD) have a
diferent gait pattern? Relationship between idiopathic toe-walking and ADHD].
AB - INTRODUCTION: Idiopathic toe-walking (ITW) is described as a gait pattern with no
contact between the heels and the ground in children older than 3years. The
diagnosis is clinical, making it necessary to rule out other neurological and
orthopaedic conditions. A relationship between ITW and vestibular dysfunction
and/or proprioceptive sensibility has been proposed. Children with
neurodevelopmental disorders (autism, language and cognitive disorders) often
have ITW. OBJECTIVES: To determine the frequency of ITW in children with
attention deficit disorder and hyperactivity (ADHD). PATIENTS AND METHOD: A study
was conducted on children diagnosed with ADHD, with normal neurological
examination, with no alterations in MRI scan, cognitive disorder or autism. A
complete clinical anamnesis was performed and Achilles shortening was measured
with a goniometer. RESULTS: The study included 312 children with a mean age of 11
years (73.7% boys). The ADHD combined subtype was the most frequent (53.8%),
followed by the inattentive (44.9%), and hyperactive (1.3%). ITW was observed in
20.8% of patients, particularly in the combined subtype (P=.054). Only 32 of them
(49.2%) had Achilles shortening. ITW was associated with sociability disorders
(P=.01), absence of pain in legs (P=.022), and family history of ITW (P=.004).
Only 11% had previously visited a doctor for this reason. CONCLUSIONS: As in
other neurodevelopmental disorders, children with ADHD have frequently more ITW
and Achilles shortening than controls, especially if they presented with a social
communication disorder or a family history of ITW. An early diagnosis is
essential to establish effective treatments.
PMID- 28705638
TI - Laparoscopic-assisted Duhamel procedure with ex-anal rectal transection for total
colonic aganglionosis.
AB - PURPOSE: Laparoscopic-assisted Duhamel procedure has a larger anastomosis and a
reservoir which allows early recovery of defecation frequency, but concerns have
been raised regarding the long operative time, high incidence of pouchitis and
Hirschsprung associated enterocolitis (HAEC). The purpose of this study was to
evaluate the postoperative complications and functional outcomes for patients
with TCA undergoing modified laparoscopic-assisted Duhamel procedure (MLDP) with
ex-abdominal partial colectomy and ex-anal rectal transection. METHODS: From 2011
to 2014, 16 patients with TCA who underwent MLDP were reviewed at our
institution. Main modified techniques were to mobilize partial bowel through
abdominal stoma opening, mobilize remaining colon, and dissect the retro-rectal
space using laparoscopy, pull out and transect rectum ex-anally using a linear
stapling device for creation of a short rectal pouch of 35~45mm. Seven patients
who underwent classical laparoscopic Duhamel procedure (CLDP) with a long rectal
pouch of 50-60mm between 2009 and 2011 were used as control group. Data were
collected including demographics, laparoscopic technique, operative time, stool
frequency, complications and continence outcomes. RESULTS: The operative time in
MLDP group was significantly shorter than control group (3.0h vs. 4.7h, p=0.02).
The incidence of postoperative HAEC in MLDP group was lower than control group
(12.5% versus 42.9%; p=0.03) within the second postoperative year. Two patients
(28.6%) experienced episodes of pouchitis in CLDP group and none was found in
MLDP group. There was no significant difference in overall functional outcome
between two groups, but the performance of MLDP group was better in terms of
diapers required than CLDP group (1.80+/-0.45 vs. 1.00+/-0.64; p=0.02). All
patients after 4years of age had a normal defecation frequency in both groups.
CONCLUSIONS: MLDP is a safe, simple, and reliable technique for TCA. It has fewer
postoperative complications due to the short rectal pouch. However, longer follow
up and a larger sample size are necessary to prove the efficacy in the treatment
of TCA. LEVEL OF EVIDENCE: Level 3.
PMID- 28705639
TI - Genetic and epigenetic heterogeneity and the impact on cancer relapse.
AB - Acute myeloid leukemia (AML) is an aggressive hematopoietic malignancy with an
exceedingly poor prognosis: a 5-year overall survival rate of 40%-45% in the
young and a 5-year survival rate of less than 10% in the elderly (>60 years of
age). Although a high percentage of patients enters complete remission after
chemotherapeutic intervention, the majority of patients relapse within 3 years.
Such stark prognostic outcomes highlight the need for additional clinical
research, basic discovery, and molecular delineation of the etiologies and
mechanisms behind responses to therapy that lead to relapse. Here, we summarize
recent discoveries in tumor heterogeneity at the genetic and epigenetic levels
and their independent molecular trajectories and dynamics in response to therapy.
These new discoveries may have significant implications for understanding,
monitoring, and treating leukemia and other cancers.
PMID- 28705640
TI - Fatal Clostridium septicum multifocal myonecrosis in a previously healthy 25-year
old man: Role of NSAIDs?
PMID- 28705641
TI - Design, synthesis, biological evaluation and molecular modelling studies of novel
diaryl substituted pyrazolyl thiazolidinediones as potent pancreatic lipase
inhibitors.
AB - A series of novel diaryl substituted pyrazolyl 2,4-thiazolidinediones were
synthesized via reaction of appropriate pyrazolecarboxaldehydes with 2,4
thiazolidinedione (TZD) and nitrobenzyl substituted 2,4-thiazolidinedione. The
resulting compounds were screened in vitro for pancreatic lipase (PL) inhibitory
activity. Two assay protocols were performed viz., methods A and B using p
nitrophenyl butyrate and tributyrin as substrates, respectively. Compound 11e
exhibited potent PL inhibitory activity (IC50=4.81uM and Xi50=10.01, respectively
in method A and B), comparable to that of the standard drug, orlistat
(IC50=0.99uM and Xi50=3.72). Presence of nitrobenzyl group at N-3 position of TZD
and nature of substituent at para position of phenyl ring at C-3 position of
pyrazole ring notably affected the PL inhibitory activity of the tested
compounds. Enzyme inhibition kinetics of 11e revealed its reversible competitive
inhibition, similar to that of orlistat. Molecular docking studies validated the
rationale of pharmacophoric design and are in accordance to the in vitro results.
Compound 11e exhibited a potential MolDock score of -153.349kcal/mol. Further,
the diaryl pyrazolyl wing exhibited hydrophobic interactions with the amino acids
of the hydrophobic lid domain. Moreover, the carbonyl group at 2nd position of
the TZD ring existed adjacent to Ser 152 (~3A) similar to that of orlistat. A
10ns molecular dynamics simulation of 11e-PL complex revealed a stable binding
conformation of 11e in the active site of PL (Maximum RMSD~3A). The present study
identified novel thiazolidinedione based leads with promising PL inhibitory
activity. Further development of the leads might result in potent PL inhibitors.
PMID- 28705642
TI - Corrigendum to "Synthesis and carbonic anhydrase inhibitory properties of novel
chalcone substituted benzenesulfonamides" [Bioorg. Med. Chem. Lett. 26 (2016)
5867-5870].
PMID- 28705643
TI - GPCRs and EGFR - Cross-talk of membrane receptors in cancer.
AB - G protein-coupled receptors (GPCRs) and receptor-tyrosine kinases (RTKs) are two
important classes of cell surface receptors proven to be highly tractable as drug
targets. Both receptor classes are involved in various complex (patho-)
physiological processes in the human body including cellular growth and
differentiation. More recently, accumulating data suggest that GPCR-induced
activation of EGFR, the prototyp of RTKs represents a major mechanism in various
cancers. The present review will focus on this cross-talk with particular
emphasis on intracellular scaffold proteins regulating EGFR transactivation. It
will give an overview about the current status of the research and future
directions, highlight recent trends in the field, and discuss the potential of
therapeutic strategies combining GPCR and EGFR targeting on the one hand and
specific targeting of the cross-talk on the other hand in cancer therapy.
PMID- 28705644
TI - Discovery of DS79182026: A potent orally active hepcidin production inhibitor.
AB - Hepcidin has emerged as the central regulatory molecule of systemic iron
homeostasis. Inhibition of hepcidin could be a strategy favorable to treating
anemia of chronic disease (ACD). We report herein the synthesis and structure
activity relationships (SARs) of a series of benzisoxazole compounds as orally
active hepcidin production inhibitors. The optimization study of multi kinase
inhibitor 1 led to a potent and bioavailable hepcidin production inhibitor 38
(DS79182026), which showed serum hepcidin lowering effects in a mouse IL-6
induced acute inflammatory model.
PMID- 28705645
TI - Assessing the impact of program volume and composition on waiting list outcomes
in pediatric lung transplantation.
PMID- 28705646
TI - Reverse histologic remodeling after mechanical unloading of failing hearts in
children with dilated cardiomyopathy.
PMID- 28705647
TI - Telomerase activity in patients with stage 2-5D chronic kidney disease.
AB - BACKGROUND: Molecular mechanisms of increased cardiovascular mortality in chronic
kidney disease (CKD) associated with biological age are not well understood.
Recent studies support the hypothesis that common factors responsible for this
phenomenon are cellular aging and telomere dysfunction. OBJECTIVES: The purpose
of this study was to investigate the relation between telomerase activity and CKD
stages. METHODS: The study included 120 patients who were followed-up for CKD
stage 2-5D, composed of 30 patients of each stage and 30 healthy volunteers
without any known disease who were admitted to our hospital for routine check
ups. Telomerase activity in peripheral blood mononuclear cells (PBMC) was
measured using the TRAP assay. RESULTS: A significant difference was observed for
telomerase activity in PBMC between groups. The detected levels were lowest in
the healthy control group (0.15+/-0.02), and highest in CKD stage 5D patients
(0.23+/-0.04). In CKD patients, telomerase activity in PBMC was positively
correlated with the CKD stage, serum creatinine, potassium and parathormone
levels, and negatively correlated with estimated glomerular filtration rate
(eGFR), body mass index (BMI), platelet count and serum calcium levels. According
to the linear regression analysis, independent predictors for high telomerase
activity in CKD patients were eGFR and BMI. CONCLUSION: Telomerase activity in
PBMC increases with advancing CKD stage in CKD patients. Increased telomerase
activity in PBMC is associated with eGFR and BMI.
PMID- 28705648
TI - Unnoticed iron overload leading to irreversible pancreatic damage.
PMID- 28705649
TI - A new approach for endoscopic neurolysis of the suprascapular nerve at the
spinoglenoid notch: A preliminary cadaver study.
AB - The suprascapular nerve (SSN) can become compressed at its 2 scapular
attachments: the suprascapular and the spinoglenoid notch. The objective of this
study was to describe a new arthroscopic approach for SSN neurolysis at the
spinoglenoid notch. Ten cadaver shoulders were used. Two were dissected to
simulate the "classical" arthroscopic approach and to help in the creation of a
new "direct medial retrospinal" approach. Eight other shoulders were used to
validate this new approach, with control of the whole juxta-glenoid course of the
SSN as criterion of success. The retrospinal posterior approach allowed the
entire juxta-glenoid segment of the SSN to be explored in 6 cases out of 8. One
exploration was incomplete, another not feasible. SSN neurolysis at the
spinoglenoid notch was feasible in cadavers on a retrospinal approach.
PMID- 28705650
TI - Shoulder function in patients with deltoid paralysis and intact rotator cuff.
AB - INTRODUCTION/HYPOTHESIS: The purpose of this study is to determine the mid/long
term shoulder function in patients with complete deltoid paralysis and intact
rotator cuff. 27 patients with at least 2-years FU were included. MATERIALS AND
METHODS: Outcome measures included pain, range of motion (including the
swallowtail test STT), deltoid extension lag test DELT and Bertelli test),
subjective fatigability using the injured shoulder and postoperative modified
Neer ratings. RESULTS: At an average 68 months FU, mean shoulder abduction was
131 degrees , flexion 153 degrees , external rotation with the arm at the side 58
degrees and 58 degrees with the arm abducted. All patients reported quick
fatiguability with repetitive use of the injured arm which did not change over
time. Average pain score was 2. Eighteen patients had positive STT and DELT tests
and all patients had positive Bertelli test. DISCUSSION: This study demonstrates
that patients with deltoid paralysis and intact rotator cuff do maintain most of
their shoulder function and this is sustained over time. LEVEL OF EVIDENCE: Level
IV; prognostic Study: case series.
PMID- 28705651
TI - Pediatric Anticoagulation: Time for a New Paradigm?
PMID- 28705652
TI - Measuring Resilience in the Adolescent Population: A Succinct Tool for Outpatient
Adolescent Health.
AB - OBJECTIVE: To create a valid tool to measure adolescent resilience, and to
determine if this tool correlates with current participation in risk behaviors
and prior adverse childhood events. STUDY DESIGN: One hundred adolescents were
recruited from primary care clinics in New Jersey for this cross-sectional study.
A "7Cs tool" was developed to measure resilience using the 7Cs model of
resilience. All participants completed the 7Cs tool, the Adverse Childhood Events
Survey, and the Health Survey for Adolescents to identify current risk behaviors.
Demographic and background data were also collected. To assess the validity of
the 7Cs tool, Cronbach alpha, principal factor analysis, Spearman coefficients,
and sensitivity analyses were conducted. The chi2 test and ORs were used to
determine if any relationships exist between resilience and prior adverse
childhood events and risk taking behaviors. RESULTS: Participants ranged from 13
to 21 years old (65% female). Internal consistency was established using Cronbach
alpha (0.7). Lower resilience correlated with higher adverse childhood events (P
= .008) and Health Survey for Adolescents scores (P < .001). Lower resilience was
associated with increased problems in school (OR 2.6; P = .021), drug use (OR
4.0; P = .004), violent behavior (OR 3.7; P = .002), recent depression (OR 5.0; P
< .001), and suicidality (OR 4.1; P = .009). Higher resilience was associated
with participation in exercise (P = .001) and activities (P = .01). CONCLUSIONS:
The 7Cs tool is an internally validated tool that may be used to screen
adolescent resilience and guide pediatricians' counseling against risk behaviors.
Further studies will evaluate resilience-building interventions based on results
from this study.
PMID- 28705653
TI - Solving the Extubation Equation: Successfully Weaning Infants Born Extremely
Preterm from Mechanical Ventilation.
PMID- 28705654
TI - Can We Define Bronchopulmonary Dysplasia?
PMID- 28705655
TI - Twenty-Five Year Survival of Children with Intellectual Disability in Western
Australia.
AB - OBJECTIVES: To investigate survival up to early adulthood for children with
intellectual disability and compare their risk of mortality with that of children
without intellectual disability. STUDY DESIGN: This was a retrospective cohort
study of all live births in Western Australia between January 1, 1983 and
December 31, 2010. Children with an intellectual disability (n = 10 593) were
identified from the Western Australian Intellectual Disability Exploring Answers
Database. Vital status was determined from linkage to the Western Australian
Mortality database. Kaplan-Meier product limit estimates and 95% CIs were
computed by level of intellectual disability. Hazard ratios (HRs) and 95% CIs
were calculated from Cox proportional hazard regression models adjusting for
potential confounders. RESULTS: After adjusting for potential confounders,
compared with those without intellectual disability, children with intellectual
disability had a 6-fold increased risk of mortality at 1-5 years of age (adjusted
HR [aHR] = 6.0, 95%CI: 4.8, 7.6), a 12-fold increased risk at 6-10 years of age
(aHR = 12.6, 95% CI: 9.0, 17.7) and a 5-fold increased risk at 11-25 years of age
(aHR = 4.9, 95% CI: 3.9, 6.1). Children with severe intellectual disability were
at even greater risk. No difference in survival was observed for Aboriginal
children with intellectual disability compared with non-Aboriginal children with
intellectual disability. CONCLUSIONS: Although children with intellectual
disability experience higher mortality at all ages compared with those without
intellectual disability, the greatest burden is for those with severe
intellectual disability. However, even children with mild to moderate
intellectual disability have increased risk of death compared with unaffected
children.
PMID- 28705656
TI - Impact of Enteroviral Polymerase Chain Reaction Testing on Length of Stay for
Infants 60 Days Old or Younger.
AB - OBJECTIVE: To determine the impact of a cerebrospinal fluid enterovirus
polymerase chain reaction (PCR) test performance on hospital length of stay (LOS)
in a large multicenter cohort of infants undergoing evaluation for central
nervous system infection. STUDY DESIGN: We performed a planned secondary analysis
of a retrospective cohort of hospitalized infants <=60 days of age who had a
cerebrospinal fluid culture obtained at 1 of 18 participating centers (2005
2013). After adjustment for patient age and study year as well as clustering by
hospital center, we compared LOS for infants who had an enterovirus PCR test
performed vs not performed and among those tested, for infants with a positive vs
negative test result. RESULTS: Of 19 953 hospitalized infants, 4444 (22.3%) had
an enterovirus PCR test performed and 945 (21.3% of tested infants) had positive
test results. Hospital LOS was similar for infants who had an enterovirus PCR
test performed compared with infants who did not (incident rate ratio 0.98 hours;
95% CI 0.89-1.06). However, infants PCR positive for enterovirus had a 38%
shorter LOS than infants PCR negative for enterovirus (incident rate ratio 0.62
hours; 95% CI 0.57-0.68). No infant with a positive enterovirus PCR test had
bacterial meningitis (0%; 95% CI 0-0.4). CONCLUSIONS: Although enterovirus PCR
testing was not associated with a reduction in LOS, infants with a positive
enterovirus PCR test had a one-third shorter LOS compared with infants with a
negative enterovirus PCR test. Focused enterovirus PCR test use could increase
the impact on LOS for infants undergoing cerebrospinal fluid evaluation.
PMID- 28705657
TI - Role of glutathione in the regulation of epigenetic mechanisms in disease.
AB - Epigenetics is a rapidly growing field that studies gene expression modifications
not involving changes in the DNA sequence. Histone H3, one of the basic proteins
in the nucleosomes that make up chromatin, is S-glutathionylated in mammalian
cells and tissues, making Gamma-L-glutamyl-L-cysteinylglycine, glutathione (GSH),
a physiological antioxidant and second messenger in cells, a new post
translational modifier of the histone code that alters the structure of the
nucleosome. However, the role of GSH in the epigenetic mechanisms likely goes
beyond a mere structural function. Evidence supports the hypothesis that there is
a link between GSH metabolism and the control of epigenetic mechanisms at
different levels (i.e., substrate availability, enzymatic activity for DNA
methylation, changes in the expression of microRNAs, and participation in the
histone code). However, little is known about the molecular pathways by which GSH
can control epigenetic events. Studying mutations in enzymes involved in GSH
metabolism and the alterations of the levels of cofactors affecting epigenetic
mechanisms appears challenging. However, the number of diseases induced by
aberrant epigenetic regulation is growing, so elucidating the intricate network
between GSH metabolism, oxidative stress and epigenetics could shed light on how
their deregulation contributes to the development of neurodegeneration, cancer,
metabolic pathologies and many other types of diseases.
PMID- 28705659
TI - Update on amino acid transporter functions and on possible amino acid sensing
mechanisms in plants.
AB - Amino acids are essential components of plant metabolism, not only as
constituents of proteins, but also as precursors of important secondary
metabolites and as carriers of organic nitrogen between the organs of the plant.
Transport across intracellular membranes and translocation of amino acids within
the plant is mediated by membrane amino acid transporters. The past few years
have seen the identification of a new family of amino acid transporters in
Arabidopsis, the characterization of intracellular amino acid transporters, and
the discovery of new roles for already known proteins. While amino acid
metabolism needs to be tightly coordinated with amino acid transport activity and
carbohydrate metabolism, no gene involved in amino acid sensing in plants has
been unequivocally identified to date. This review aims at summarizing the recent
data accumulated on the identity and function of amino acid transporters in
plants, and discussing the possible identity of amino acid sensors based on data
from other organisms.
PMID- 28705658
TI - Disturbance of redox homeostasis in Down Syndrome: Role of iron dysmetabolism.
AB - Down Syndrome (DS) is the most common genetic form of intellectual disability
that leads in the majority of cases to development of early-onset Alzheimer-like
dementia (AD). The neuropathology of DS has several common features with AD
including alteration of redox homeostasis, mitochondrial deficits, and
inflammation among others. Interestingly, some of the genes encoded by chromosome
21 are responsible of increased oxidative stress (OS) conditions that are further
exacerbated by decreased antioxidant defense. Previous studies from our groups
showed that accumulation of oxidative damage is an early event in DS
neurodegeneration and that oxidative modifications of selected proteins affects
the integrity of the protein degradative systems, antioxidant response, neuronal
integrity and energy metabolism. In particular, the current review elaborates
recent findings demonstrating the accumulation of oxidative damage in DS and we
focus attention on specific deregulation of iron metabolism, which affects both
the central nervous system and the periphery. Iron dysmetabolism is a well
recognized factor that contributes to neurodegeneration; thus we opine that
better understanding how and to what extent the concerted loss of iron
dyshomeostasis and increased OS occur in DS could provide novel insights for the
development of therapeutic strategies for the treatment of Alzheimer-like
dementia.
PMID- 28705660
TI - Prevalence of Diagnosed Dry Eye Disease in the United States Among Adults Aged 18
Years and Older.
AB - PURPOSE: To provide current estimates of the prevalence of diagnosed dry eye
disease (DED) and associated demographics among US adults aged >=18 years.
DESIGN: Cross-sectional, population-based survey. METHODS: Data were analyzed
from 75 000 participants in the 2013 National Health and Wellness Survey to
estimate prevalence/risk of diagnosed DED overall, and by age, sex, insurance,
and other demographic factors. We weighted the observed DED prevalence to project
estimates to the US adult population and examined associations between
demographic factors and DED using multivariable logistic regression. RESULTS:
Based on weighted estimates, 6.8% of the US adult population was projected to
have diagnosed DED (~16.4 million people). Prevalence increased with age (18-34
years: 2.7%; >=75 years: 18.6%) and was higher among women (8.8%; ~11.1 million)
than men (4.5%; ~5.3 million). After adjustment, there were no substantial
differences in prevalence/risk of diagnosed DED by race, education, or US census
region. However, there was higher risk of diagnosed DED among those aged 45-54
years (odds ratio [OR]: 1.95; 95% confidence interval [CI]: 1.74-2.20) and >=75
years (OR: 4.95; 95% CI: 4.26-5.74), vs those aged 18-34 years. Risk was also
higher among women vs men (OR: 2.00; 95% CI: 1.88-2.13) and insured vs uninsured
participants (OR: 2.12; 95% CI: 1.85-2.43 for those on government and private
insurance vs none). CONCLUSIONS: We estimate that >16 million US adults have
diagnosed DED. Prevalence is higher among women than men, increases with age, and
is notable among those aged 18-34 years.
PMID- 28705661
TI - Canaliculorhinostomy-Indications and Surgical Results.
AB - PURPOSE: To report the surgical results of canaliculorhinostomy for patients with
distal canalicular obstruction and lacking a structurally functional lacrimal sac
who would otherwise require a conjunctivodacryocystorhinostomy (CDCR) with Jones
tube placement. DESIGN: Retrospective observational case series. METHODS:
Setting: Single tertiary institution. PERIOD: November 1994 to June 2011. PATIENT
POPULATION: Sixteen patients with canalicular obstruction at or beyond 8 mm from
the punctum, with an absent or unidentifiable lacrimal sac. INTERVENTION:
Patients underwent canaliculorhinostomy, whereby direct anastomosis of the
canaliculi or common canaliculus to the nasal mucosa was performed. MAIN OUTCOME
MEASURES: Anatomic and functional success. RESULTS: Our study comprised 16
patients with a mean age of 44.9 +/- 21.9 years. Ten (62.5%) were female and 6
(37.5%) male. Mean duration of follow-up was 7.8 years. Causes of an absent or
unidentifiable lacrimal sac included previous trauma (n = 8, 50.0%), previous
dacryocystorhinostomy (n = 4, 25.0%), chronic dacryocystitis (n = 3, 18.8%), and
previous dacryocystectomy (n = 1, 6.2%). Anastomoses between the upper and lower
canaliculi and the nasal mucosa was performed in 6 patients, while that between
the common canaliculus and nasal mucosa was performed in 10. Anatomic and
functional success rates were 87.5% (n = 14) and 81.3% (n = 13), respectively.
CONCLUSION: Canaliculorhinostomy has reasonable success rates and provides an
effective surgical alternative for a group of patients in whom CDCR with Jones
tube placement would otherwise have been indicated.
PMID- 28705662
TI - Transcriptional response of the extremophile red alga Cyanidioschyzon merolae to
changes in CO2 concentrations.
AB - Cyanidioschyzon merolae (C. merolae) is an acidophilic red alga growing in a
naturally low carbon dioxide (CO2) environment. Although it uses a ribulose 1,5
bisphosphate carboxylase/oxygenase with high affinity for CO2, the survival of C.
merolae relies on functional photorespiratory metabolism. In this study, we
quantified the transcriptomic response of C. merolae to changes in CO2
conditions. We found distinct changes upon shifts between CO2 conditions, such as
a concerted up-regulation of photorespiratory genes and responses to carbon
starvation. We used the transcriptome data set to explore a hypothetical CO2
concentrating mechanism in C. merolae, based on the assumption that
photorespiratory genes and possible candidate genes involved in a CO2
concentrating mechanism are co-expressed. A putative bicarbonate transport
protein and two alpha-carbonic anhydrases were identified, which showed enhanced
transcript levels under reduced CO2 conditions. Genes encoding enzymes of a PEPCK
type C4 pathway were co-regulated with the photorespiratory gene cluster. We
propose a model of a hypothetical low CO2 compensation mechanism in C. merolae
integrating these low CO2-inducible components.
PMID- 28705663
TI - Creativity on tap? Effects of alcohol intoxication on creative cognition.
AB - Anecdotal reports link alcohol intoxication to creativity, while cognitive
research highlights the crucial role of cognitive control for creative thought.
This study examined the effects of mild alcohol intoxication on creative
cognition in a placebo-controlled design. Participants completed executive and
creative cognition tasks before and after consuming either alcoholic beer (BAC of
0.03) or non-alcoholic beer (placebo). Alcohol impaired executive control, but
improved performance in the Remote Associates Test, and did not affect divergent
thinking ability. The findings indicate that certain aspects of creative
cognition benefit from mild attenuations of cognitive control, and contribute to
the growing evidence that higher cognitive control is not always associated with
better cognitive performance.
PMID- 28705664
TI - Complete Atrioventricular Canal Defect: Towards a More Physiological Repair.
AB - We describe a more physiological technique of complete atrioventricular septal
defect repair which restores normal heart anatomy with the offset between the
insertions of the mitral and tricuspid valves. This technique overcomes the
drawbacks of the previous approaches, and may improve surgical outcomes,
particularly in small infants with high ventricular septal defect component or
dextroposed aorta.
PMID- 28705665
TI - Bloodstream infections due to extended-spectrum beta-lactamase-producing
Enterobacteriaceae among patients with malignancy: a systematic review and meta
analysis.
AB - Extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE) are an
increasing cause of resistant infections among patients with malignancy. This
study sought to estimate the prevalence of bloodstream infections (BSIs) caused
by ESBL-PE in this population and to examine regional and temporal differences.
The PubMed and EMBASE databases (to 30 April 2016) were searched to identify
studies reporting ESBL-PE BSI rates among patients with malignancies. Of 593 non
duplicate reports, 22 studies providing data on 5650 BSI cases satisfied the
inclusion criteria. Among all BSIs the pooled prevalence of ESBL-PE was 11% (95%
CI 8-15%) and among Gram-negative BSIs it was 21% (95% CI 16-27%). Among patients
with haematological malignancies, the pooled ESBL-PE prevalence was 11% (95% CI 8
15%), whereas no studies providing specific data on patients with solid tumours
were identified. Stratifying per geographic region, the pooled prevalence was 7%
each in Europe (95% CI 5-11%), the Eastern Mediterranean region (95% CI 4-11%)
and South America (95% CI 2-14%), 10% in the Western Pacific region (95% CI 4
19%) and 30% in Southeast Asia (95% CI 18-44%). Importantly, there was a 7.1%
annual increase in the ESBL-PE incidence (P = 0.004). Overall, ca. 1 in 10 BSIs
in patients with malignancy is caused by ESBL-PE and in some areas this rate can
be as high as 1 in 3 cases. Additionally, the incidence of these resistant
infections is rising. These findings should be considered when selecting
empirical antimicrobial therapy and should prompt strict adherence to
antimicrobial stewardship.
PMID- 28705666
TI - In-vitro activity of ceftolozane/tazobactam against Pseudomonas aeruginosa and
Enterobacteriaceae isolates recovered from hospitalized patients in Germany.
AB - To evaluate the activity of ceftolozane/tazobactam compared with other broad
spectrum antimicrobials against Pseudomonas aeruginosa and Enterobacteriaceae,
497 non-duplicate P. aeruginosa and 802 Enterobacteriaceae clinical isolates were
consecutively collected during the period from September 2014 to April 2015 from
patients in Germany with bloodstream, lower respiratory tract, intra-abdominal or
urinary tract infections. Antimicrobial susceptibility testing was performed by
broth microdilution. Results were interpreted according to EUCAST criteria.
Ceftolozane/tazobactam showed good activity against Escherichia coli and
Klebsiella pneumoniae isolates with MIC50/90 values of 0.25/0.5 mg/L and 0.25/1
mg/L, respectively. Comparatively, piperacillin/tazobactam, ceftazidime and
meropenem MIC50/90 values were 2/8 mg/L, 0.25/8 mg/L and <=0.03/ <= 0.03 mg/L,
respectively, for E. coli, and 2/16 mg/L, 0.12/8 mg/L, and <=0.03/ <= 0.03 mg/L,
respectively, for K. pneumoniae isolates. The activity of ceftolozane/tazobactam
against P. aeruginosa was superior to that of other antipseudomonal
antimicrobials. Based on MIC50/90 values, ceftolozane/tazobactam (0.5/2 mg/L) was
more active than piperacillin/tazobactam (8/64 mg/L), ceftazidime (2/16 mg/L),
cefepime (2/16 mg/L) or meropenem (0.5/8 mg/L). In conclusion,
ceftolozane/tazobactam exhibited the best in vitro potency of the antibiotics
tested against P. aeruginosa, including isolates that were resistant to
piperacillin/tazobactam, cefepime, ceftazidime, doripenem, meropenem,
ciprofloxacin, levofloxacin, amikacin, and tobramycin. Ceftolozane/tazobactam has
the potential to become a useful addition to the limited armamentarium of drugs
that can be used to treat this problem pathogen.
PMID- 28705667
TI - Clinical characteristics of bacteraemia caused by Burkholderia cepacia complex
species and antimicrobial susceptibility of the isolates in a medical centre in
Taiwan.
AB - This study investigated the clinical characteristics and outcomes of bacteraemia
due to Burkholderia cepacia complex (BCC) species among 54 patients without
cystic fibrosis from January 2013 to February 2015. BCC isolates were identified
to the species level by the Bruker Biotyper MALDI-TOF MS system and by sequencing
analysis of the 16S rRNA and recA genes. Antimicrobial susceptibilities of the
isolates were determined by the agar dilution method. Sequencing of the recA gene
in the 54 blood isolates revealed 37 (68.5%) isolates of B. cenocepacia, 9
(16.7%) of B. cepacia, 4 (7.4%) of B. multivorans and one isolate each of B.
arboris, B. pseudomultivorans, B. seminalis, and B. vietnamiensis. The overall
performance of the Bruker Biotyper MALDI-TOF MS system for correctly identifying
the 54 BCC isolates to the species level was 79.6%, which was better than that
(16.7%) by 16S RNA sequencing analysis. Bacteraemic pneumonia (n = 23, 42.6%) and
catheter-related bacteraemia (n = 21, 38.9%) were the most common types of
infection. Higher rates of ceftazidime and meropenem resistance were found in B.
cepacia isolates (33.3% and 22.2%, respectively) than in isolates of B.
cenocepacia (21.6% and 10.8%, respectively) and other species (12.5% and 12.5%,
respectively). Overall, the 30-day mortality rate was 38.9% (21/54). Bacteraemia
caused by BCC species other than B. cenocepacia and B. cepacia (adjusted odds
ratio [aOR] 20.005, P = 0.024) and high SOFA score (aOR 1.412, P = 0.003) were
predictive of higher 30-day mortality. Different BCC species are associated with
different outcomes of bacteraemia and exhibit different susceptibility patterns.
PMID- 28705668
TI - In-vitro activity of the novel fluorocycline eravacycline against carbapenem non
susceptible Acinetobacter baumannii.
AB - The activity of eravacycline was compared with that of anti-Acinetobacter
reference antimicrobials against carbapenem non-susceptible Acinetobacter
baumannii isolates associated with an acquired OXA or up-regulation of the
intrinsic OXA-51-like enzyme. Antimicrobial susceptibility testing was performed
by broth microdilution of 286 non-duplicate, carbapenem non-susceptible A.
baumannii isolates to eravacycline, amikacin colistin, doxycycline, imipenem,
levofloxacin, meropenem, minocycline, sulbactam, tigecycline and tobramycin.
Eravacycline showed greater activity than the comparators of the tetracycline
class, levofloxacin, amikacin, tobramycin and colistin. The eravacycline MIC50/90
values were 0.5/1 mg/L and those for tigecycline, minocycline and doxycycline
were 1/2, 4/8 and 32/ >= 64 mg/L, respectively. In conclusion, eravacycline was
the most potent antibiotic of those tested against A. baumannii, including
isolates that were resistant to sulbactam, imipenem/meropenem, levofloxacin and
amikacin/tobramycin. Eravacycline has the potential to become a useful addition
to the limited armamentarium of drugs that can be used to treat this problem
pathogen.
PMID- 28705669
TI - Activity of temocillin against CTX-M-producing Escherichia coli and Klebsiella
pneumoniae from Germany.
PMID- 28705670
TI - Empiric antibiotic protocols for cancer patients with neutropenia: a single
center study of treatment efficacy and mortality in patients with bacteremia.
AB - BACKGROUND: There are several empiric antibiotic treatment options for febrile
neutropenia, yet there is no universally-accepted initial protocol. We aimed to
assess the performance of a protocol (piperacillin, gentamicin and cefazolin)
introduced over 40 years ago and compare its coverage against bacteria isolated
from blood of neutropenic patients with that of various commonly used antibiotic
treatment protocols. METHODS: Adults with neutropenia admitted between 2003 and
2012 to the hemato-oncologic departments and in whom blood cultures were taken on
admission were included. Appropriateness of several common antibiotic protocols
was assessed based on the susceptibility of the blood isolates. Crude mortality
rates were computed by the susceptibility of bacteria isolated from patients'
blood to the actual treatment given. RESULTS: In total, 180 admissions of
neutropenic patients (95 in patients who had fever above 38 degrees C) with
positive blood cultures were analyzed. The actual antibiotic regimen prescribed
was deemed appropriate in 82% of bacteremia episodes. The recommended
institutional protocol was used in 62% of bacteremia episodes in neutropenic
patients. This protocol would have been appropriate in 85% of all neutropenic
bacteremia episodes and 89% of episodes in febrile neutropenia patients compared
with piperacillin/tazobactam (79%, P = 0.13 and 76%, P = 0.002, respectively) and
imipenem (93%, P = 0.004 and 92%, P = 0.74, respectively). Isolation of bacteria
resistant to the actual antibiotic treatment given was associated with higher
mortality at one week and at 30 days. CONCLUSION: Common current antibiotic
regimens provide similar coverage among febrile neutropenic patients, whereas
broad spectrum antibiotic combinations maximize coverage among neutropenic
patients.
PMID- 28705671
TI - Antimicrobial resistance in West Africa: a systematic review and meta-analysis.
AB - Growing data suggest that antimicrobial-resistant bacterial infections are common
in low- and middle-income countries. This review summarises the microbiology of
key bacterial syndromes encountered in West Africa and estimates the prevalence
of antimicrobial resistance (AMR) that could compromise first-line empirical
treatment. We systematically searched for studies reporting on the epidemiology
of bacterial infection and prevalence of AMR in West Africa within key clinical
syndromes. Within each syndrome, the pooled proportion and 95% confidence
interval were calculated for each pathogen-antibiotic pair using random-effects
models. Among 281 full-text articles reviewed, 120 met the eligibility criteria.
The majority of studies originated from Nigeria (70; 58.3%), Ghana (15; 12.5%)
and Senegal (15; 12.5%). Overall, 43 studies (35.8%) focused on urinary tract
infections (UTI), 38 (31.7%) on bloodstream infections (BSI), 27 (22.5%) on
meningitis, 7 (5.8%) on diarrhoea and 5 (4.2%) on pneumonia. Children comprised
the majority of subjects. Studies of UTI reported moderate to high rates of AMR
to commonly used antibiotics including evidence of the emergence of cephalosporin
resistance. We found moderate rates of AMR among common bloodstream pathogens to
typical first-line antibiotics including ampicillin, cotrimoxazole, gentamicin
and amoxicillin/clavulanate. Among S. pneumoniae strains isolated in patients
with meningitis, levels of penicillin resistance were low to moderate with no
significant resistance noted to ceftriaxone or cefotaxime. AMR was common in this
region, particularly in hospitalized patients with BSI and both outpatient and
hospitalized patients with UTI. This raises concern given the limited diagnostic
capability and second-line treatment options in the public sector in West Africa.
PMID- 28705672
TI - Role of vancomycin in the treatment of bacteraemia and meningitis caused by
Elizabethkingia meningoseptica.
AB - Elizabethkingia meningoseptica, a Gram-negative pathogen once deemed clinically
insignificant, tends to cause infections among low-birth-weight infants and
immunocompromised patients. Previously, vancomycin was reported to cure several
patients with bacteraemia caused by E. meningoseptica. Nevertheless, some
laboratory investigations also showed considerable discordance between in vitro
vancomycin susceptibility results obtained by the disk diffusion and broth
microdilution methods against clinical E. meningoseptica isolates as determined
using the criteria for staphylococci recommended by the Clinical and Laboratory
Standards Institute (CLSI). In this review, the PubMed database (1960-2017) was
searched for studies that reported mainly cases with E. meningoseptica
bacteraemia or meningitis treated with vancomycin alone or with regimens that
included vancomycin. In addition, the in vitro synergy between vancomycin and
other agents against isolates of E. meningoseptica was reviewed. Elizabethkingia
meningoseptica bacteraemia appears not to universally respond to intravenous
(i.v.) vancomycin-only therapy, especially in patients who require haemodialysis.
If i.v. vancomycin is the favoured therapy against E. meningoseptica meningitis,
the addition of ciprofloxacin, linezolid or rifampicin might be an option to
effectively treat this difficult-to-treat infection. Further clinical studies are
needed to determine the clinical efficacy of these combination regimens for the
treatment of E. meningoseptica meningitis.
PMID- 28705673
TI - Global acquisition of genetic material from different bacteria into the
staphylococcal cassette chromosome elements of a Staphylococcus epidermidis
isolate.
AB - Staphylococcus epidermidis has been suggested as a main reservoir of methicillin
resistance and virulence genes facilitating the evolution of Staphylococcus
aureus as a successful pathogen. However, it remains a mystery where and how S.
epidermidis obtains these numerous genes to serve as the reservoir. In this
study, methicillin-resistant S. epidermidis isolate NW32 from a mastitic milk
sample was sequenced and its staphylococcal cassette chromosome (SCC) elements
were characterised. The SCC composite island covered 3.5% of the genome and
consisted of three intact SCC elements carrying resistance genes against beta
lactam antibiotics, several heavy metals and polyamines as well as genes for
utilisation of sorbitol as a carbon source. Analysis of the postulated
evolutionary route suggested that the three SCC elements were assembled from
genetic material from various bacterial species (staphylococci, streptococci,
salinicocci and Lysinibacillus) from three habitats (human, soil and cow) in
different countries (Asia, North America, South America and Europe). We propose
that the hsdS restriction-modification profile and the lack of CRISPR (clustered
regularly interspaced short palindromic repeat) sequences in this bacterium may
facilitate the genetic exchange of SCC elements among different staphylococcal
species.
PMID- 28705674
TI - Molecular bases of antifungal resistance in filamentous fungi.
AB - Invasive mould infections due to Aspergillus spp., Fusarium spp., Scedosporium
spp. and other filamentous fungi remain a significant cause of morbidity and
mortality in immunocompromised patients. Antifungal therapy is required for
successful patient management; however, limited antifungal drugs as well as the
emergence of drug resistance pose a challenge to clinicians for effective
management of these diseases. The evolution of multidrug-resistant strains owing
to selective pressure as well as intrinsically-resistant pathogenic species are a
major concern. Thus, it is necessary to gain a better insight into the antifungal
resistance mechanisms and their clinical impact. So far, the resistance
mechanisms responsible for acquired azole resistance include alteration of the
drug target and its overexpression, biofilm formation and efflux pump
upregulation. However, mechanisms responsible for polyene and echinocandin
resistance are less understood in filamentous moulds, primarily due to incomplete
correlation between in vitro susceptibility and clinical response to treatment.
The present review gives an insight into the mechanisms implicated in resistance
to different classes of antifungal agents both in human and plant pathogenic
filamentous fungi. Furthermore, the spectrum of antifungal resistance in these
filamentous fungi is highlighted.
PMID- 28705675
TI - Use of evidence-based recommendations in an antibiotic care bundle for the
intensive care unit.
AB - PURPOSE: To drive decisions on antibiotic therapy in the intensive care unit
(ICU), we developed an antibiotic care bundle (ABC-Bundle) with evidence-based
recommendations (EBRs) for antibiotic prescriptions. METHODS: We conducted a
three-step prospective study. First, a systematic review was performed of the
literature reporting EBRs for antibiotic usage in the ICU. Second, we developed
an ABC-Bundle through a two-round, RAND-modified Delphi method with an
international expert panel, including the most relevant EBRs on a 9-point Likert
scale. Those EBRs that were considered mandatory by >50% of the experts were
included in the bundle. Third, we assessed the adherence to and applicability of
the bundle in two mixed university ICUs. RESULTS: Out of 1190 potentially
relevant articles, 14 (four guidelines, four randomised controlled trials and six
systematic reviews) fulfilled the eligibility criteria. Six EBRs were classified
as relevant: 1. Provide rationale for antibiotic start; 2. Perform appropriate
microbiological sampling; 3. Prescribe empirical antibiotic therapy according to
guidelines (Day 1); 4. Review diagnosis; 5. Evaluate de-escalation based on
microbiological results (Days 2-5); and 6. Consider discontinuation of treatment
(Days 3-5). Daily adherence to the ABC-Bundle, prospectively assessed in 861 days
of therapy in 142 ICU patients, ranged from 2% to 37%. CONCLUSION: The ABC-Bundle
is a novel tool to improve delivery of appropriate antibiotic therapy to ICU
patients. The low adherence in the prospective cohorts confirms the significant
role that the ABC-Bundle could play in an antibiotic stewardship programme in the
ICU setting.
PMID- 28705676
TI - Current antifungal treatment of fusariosis.
AB - Fungi of the genus Fusarium are well known as major plant pathogens and soil
inhabitants, but also cause a broad spectrum of human infections. Fusariosis is
the second most common mould infection after aspergillosis, and keratitis is the
most encountered implantation infection in immunocompetent individuals. Natamycin
is active against Fusarium species both in vitro and in vivo, and is used along
with voriconazole as the mainstay of treatment for Fusarium keratitis.
Onychomycosis is treated with terbinafine, voriconazole and sometimes
itraconazole. Cure is possible despite high in vitro minimum inhibitory
concentrations (MICs). Recently, disseminated infections have increased
dramatically, mainly affecting severely immunocompromised patients. The
remarkable intrinsic resistance of Fusarium species to most antifungal agents
results in high mortality rates in this patient population. Recovery of
neutropenia is essential for patient survival and treatment should include
voriconazole or amphotericin B as first-line and posaconazole as salvage therapy.
PMID- 28705677
TI - Hyicin 4244, the first sactibiotic described in staphylococci, exhibits an anti
staphylococcal biofilm activity.
AB - Hyicin 4244 is a small antimicrobial peptide with a broad spectrum of activity
that was found in the culture supernatant of Staphylococcus hyicus 4244, the
genome of which was then sequenced. The bacteriocin gene cluster (hyiSABCDEFG)
was mined from its single chromosome and exhibited a genetic organization similar
to that of subtilosin A. All genes involved in hyicin 4244 biosynthesis proved to
be transcribed and encode proteins that share at least 42% similarity to proteins
encoded by the subtilosin A gene cluster. Due to its resemblance to subtilosin A
and the presence of three thioether bonds in its structure, hyicin 4244 is
assumed to be a 35-amino acid circular sactibiotic, the first to be described in
staphylococci. Hyicin 4244 inhibited 14 staphylococcal isolates from either human
infections or bovine mastitis, all biofilm formers. Hyicin 4244 significantly
reduced the number of colony-forming units (CFU) and the biofilm formation by two
strong biofilm-forming strains randomly chosen as representatives of the strains
involved in human infections and bovine mastitis. It also reduced the
proliferation and viability of sessile cells in established biofilms. Therefore,
hyicin 4244 proved not only to prevent biofilm formation by planktonic cells, but
also to penetrate the biofilm matrix in vitro, exerting bactericidal activity
against staphylococcal sessile cells. This bacteriocin has the potential to
become an alternative antimicrobial for either prevention or treatment of biofilm
related infections caused by different staphylococcal species.
PMID- 28705678
TI - Pharmacodynamics of minocycline against Acinetobacter baumannii studied in a
pharmacokinetic model of infection.
AB - Minocycline (MNO) is an old antibiotic that may have an important role in the
treatment of multidrug-resistant Gram-negative bacterial infections as the burden
of such infections increases. In this study, a single-compartment dilutional
pharmacokinetic model was used to determine the relationship between MNO exposure
and antibacterial effect, including the risk of resistance emergence, against
strains of Acinetobacter baumannii. The mean +/- standard deviation area under
the unbound drug concentration-time curve to minimum inhibitory concentration
ratio (fAUC/MIC) associated with a 24-h bacteriostatic effect was 16.4 +/- 2.6
and with a -1 log reduction in bacterial load at 24 h was 23.3 +/- 3.7. None of
the strains reached a -2 log reduction over 48 h. Changes in population profiles
were noted for two of the three strains studied, especially at fAUC/MIC ratios of
>5-15. A reasonable translational pharmacodynamic target for MNO against A.
baumannii could be an fAUC/MIC of 20-25. However, if maximum standard 24-h doses
of intravenous MNO are used (400 mg/day), many strains would be exposed to MNO
concentrations likely to change population profiles and associated with the
emergence of resistance. Either MNO combination therapy or an increased MNO dose
(>400 mg/day) should be considered when treating A. baumannii infections.
PMID- 28705679
TI - The effects of cognitive reappraisal on conditioned disgust in contamination
based OCD: An analogue study.
AB - Experimental research has shown that conditioned disgust is resistant to
extinction, which may account for the slower habituation to disgust relative to
fear in contamination-based obsessive-compulsive disorder (OCD). However, few
studies have examined the efficacy of interventions that may attenuate
conditioned disgust responses. Studies of cognitive reappraisal have demonstrated
that reinterpreting a stimulus can alter emotional responding. This technique is
based on cognitive theories which suggest that anxiety disorders arise from
biased cognitions; therefore, changing a person's thoughts will elicit durable
changes in emotional responses. Given the demonstrated effectiveness of cognitive
reappraisal, the present study examined whether cognitive reappraisal would
attenuate conditioned disgust responses. We conditioned participants high in
contamination fear (n=55) using images of neutral food items (conditioned
stimuli; CS) paired with videos of individuals vomiting (unconditioned stimuli;
US) while we obtained subjective disgust reports. After conditioning, half of the
participants were randomly assigned to cognitive reappraisal training aimed at
decreasing their emotional response to the US and CS, while the other half
received no such training. The findings showed that cognitive reappraisal
participants demonstrated a reduction in learned disgust across sessions and
further benefited from extinction. These findings suggest that cognitive
reappraisal may be an effective strategy for attenuating learned disgust.
PMID- 28705680
TI - Characterization of significant molecular determinants of virulence of
Enterovirus 71 sub-genotype B4 in Rhabdomyosarcoma cells.
AB - One of the leading causes of the hand, foot and mouth disease (HFMD) is
Enterovirus 71 (EV-A71), displaying symptoms such as fever and ulcers in children
but some strains can produce cardiopulmonary oedema which leads to death. There
is no FDA-approved vaccine for prevention of severe HFMD. The molecular
determinants of virulence for EV-A71 are unclear. It could be a single or a
combination of amino acids that determines virulence in different EV-A71
genotype/sub-genotypes. Several EV-A71 strains bearing single nucleotide (nt)
mutations were constructed and the contribution of each mutation to virulence was
evaluated. The nt(s) that contributed to significant reduction in virulence in
vitro were selected and each mutation was introduced separately into the genome
to construct the multiply mutated EV-A71 strain (MMS) which carried six
substitutions of nt(s) at the 5'-NTR (U700C), VP1-145 (E to G), VP1-98E, VP1-244K
and G64R in the vaccine seed strain that had a partial deletion within the 5'-NTR
region (nt. 475-485) of Delta11bp. In comparison to the wild type strain, the MMS
showed low virulence as it produced very low RNA copy number, plaque count, VP1
and had 105-fold higher TCID50, indicative of a promising LAV candidate that
should be further evaluated in vivo.
PMID- 28705682
TI - Increased bone matrix mineralization in treatment-naive children with
inflammatory bowel disease.
AB - Inflammatory bowel disease (IBD) affects many organ systems including the
skeleton. In children with IBD, bone mineral density (BMD) and bone turnover are
frequently low. Disturbances in bone mineralization density distribution (BMDD)
are linked to alterations in bone material strength; however, BMDD has not
previously been reported in children with chronic inflammatory disorders. The aim
of this study was to characterize BMDD based on quantitative backscatter electron
imaging in cancellous (Cn.) and cortical (Ct.) compartments from trans-iliac
biopsy samples from a cohort of 20 treatment-naive children at the time of their
IBD diagnosis (12 males, mean age 14.5+/-2.3years). The outcomes were compared to
pediatric reference BMDD data and correlation with revisited biochemical and
histomorphometric outcomes was analyzed. BMDD in treatment-naive children with
IBD was shifted toward higher calcium concentrations compared to reference: (i)
In cancellous bone, the most frequent calcium concentration (Cn.CaPeak+2.8%,
p=0.004) and the portion of highly mineralized bone (Cn.CaHigh+52%, p=0.009) were
increased. (ii) In cortical bone, the mineralization heterogeneity
(Ct.CaWidth+17.0%, p=0.001) and Ct.CaHigh (+30.4%, p=0.006) were increased. (iii)
Furthermore, significant correlations with serum alkaline phosphatase (ALP), bone
specific alkaline phosphatase (bsALP), and urinary crosslinked N-telopeptide of
type I collagen (uNTX) were observed: the higher CaMean (the average calcium
concentration), CaPeak and CaHigh, the lower were ALP, bsALP, and uNTX (p-value
from <0.001 to 0.05). Children with treatment-naive IBD have decreased bone
turnover leading to a higher bone matrix mineralization density, findings which
may contribute to compromised bone strength.
PMID- 28705681
TI - Mosquito-borne and sexual transmission of Zika virus: Recent developments and
future directions.
AB - Zika virus (ZIKV; Genus Flavivirus, Family Flaviviridae) has recently emerged in
Asia and the Americas to cause large outbreaks of human disease. The outbreak has
been characterized by high attack rates, birth defects in infants and severe
neurological complications in adults. ZIKV is transmitted to humans by Aedes
mosquitoes, but recent evidence implicates sexual transmission as playing an
important role as well. This review highlights the transmission of ZIKV in
humans, with a focus on both mosquito and sexually-transmitted routes and their
outcomes. We also discuss critical directions for future research.
PMID- 28705683
TI - Periodontal ligament fibroblasts as a cell model to study osteogenesis and
osteoclastogenesis in fibrodysplasia ossificans progressiva.
AB - Fibrodysplasia Ossificans Progressiva (FOP) is a progressive disease
characterized by periods of heterotopic ossification of soft connective tissues,
including ligaments. Though progress has been made in recent years in unraveling
the underlying mechanism, patient-derived cell models are necessary to test
potential treatment options. Periodontal ligament fibroblasts (PLF) from
extracted teeth can be used to study deviant bone modeling processes in vitro
since these cells are derived from genuine ligaments. They further provide a tool
to study the hitherto unknown role of the bone morphogenesis protein receptor
type 1 (BMPR-1) Activin A type 1 receptor ACVR1-R206H mutation in
osteoclastogenesis. To further validate this potential model, osteogenesis and
osteoclastogenesis was studied in the presence of TGF-beta/activin receptor
inhibitor GW788388. Control and FOP fibroblasts (n=6 of each) were used in
osteogenesis and osteoclastogenesis assays in the absence or presence of TGF
beta/activin receptor inhibitor GW788388. For osteogenesis, alkaline phosphatase
(ALP) activity, alizarin red staining for mineralization and qPCR for expression
of osteogenic markers was assessed. TRACP staining, multinuclearity and
expression of osteoclastogenesis markers were used as a measure of osteoclast
formation. FOP fibroblasts cultured in osteogenic medium displayed a trend of
higher ALP activity at 7days. Gene expression of ALP from FOP fibroblasts was
significantly higher at 3days. Mineralization was similar at 21days for both
groups. GW788388 did not influence mineral deposition in both groups. Osteoclast
formation was inhibited by GW788388 on plastic for both controls and FOP. On
cortical bone slices, however, osteoclast formation was significantly lowered by
GW788388, only in FOP cultures. qPCR revealed strong expression of RANKL at 7days
and a significant decline at 14 and 21days in both FOP and control cultures. In
contrast to the osteoclastogenesis results, the RANKL/OPG ratio was higher in the
presence of GW788388, only in FOP cultures. TGF-beta expression was significantly
higher at 14 and 21days compared to 7days, possibly signifying a role in later
stages of osteoclast formation. Addition of GW788388 strongly decreased TGF-beta
expression. Our study shows that periodontal ligament fibroblasts from FOP
patients displayed at most slightly enhanced in vitro osteogenesis and
osteoclastogenesis. This model could be useful to elucidate molecular mechanisms
leading to heterotopic ossification in FOP such as in the presence of specific
ACVR1-R206H activators as Activin A.
PMID- 28705684
TI - [Infectious respiratory diseases: From concepts to practical issues!]
PMID- 28705685
TI - [Fungal sinusitis].
AB - Although sinusitis affects about 20 % of the population, fungal sinusitis is
rare. Aspergillus sp. are most frequently implicated. Fungal sinusitis represents
a wide spectrum of disorders, including acute or chronic and invasive or non
invasive forms. Invasive fungal sinusitis may develop in an immunocompromised or
diabetic patient, whereas non-invasive fungal sinusitis should be considered in a
chronic situation, resistant to antibiotics in immunocompetent patients. Allergic
fungal sinusitis is related to hypersensitivity of the host to the fungus. The
diagnosis of these infections requires radiological examination and endoscopy
with mucosal biopsies examined histologically and mycologically in order to
distinguish the different types of sinusitis. In the non-invasive forms, surgical
treatment is essential, sometimes combined with antifungal and anti-inflammatory
treatment. The invasive forms require antifungal treatment, combined with surgery
in some forms, particularly mucormycosis.
PMID- 28705686
TI - Imaging Features of Patients Undergoing Active Surveillance for Ductal Carcinoma
in Situ.
AB - RATIONALE AND OBJECTIVES: The aim of this study was to describe the imaging
appearance of patients undergoing active surveillance for ductal carcinoma in
situ (DCIS). MATERIALS AND METHODS: We retrospectively identified 29 patients
undergoing active surveillance for DCIS from 2009 to 2014. Twenty-two patients
(group 1) refused surgery or were not surgical candidates. Seven patients (group
2) enrolled in a trial of letrozole and deferred surgical excision for 6-12
months. Pathology and imaging results at the initial biopsy and follow-up were
recorded. RESULTS: In group 1, the median follow-up was 2.7 years (range: 0.6
13.9 years). Fifteen patients (68%) remained stable. Seven patients (32%)
underwent additional biopsies with invasive ductal carcinoma diagnosed in two
patients after 3.9 and 3.6 years who developed increasing calcifications and new
masses. In group 2, one patient (14%) was upstaged to microinvasive ductal
carcinoma at surgery. Among the patients in both groups with calcifications (n =
26), there was no progression to invasive disease among those with stable (50%,
13/26) or decreased (19%, 5/26) calcifications. CONCLUSIONS: Among a DCIS active
surveillance cohort, invasive disease progression presented as increasing
calcifications and a new mass following more than 3.5 years of stable imaging. In
contrast, there was no progression to invasive disease among cases of DCIS with
stable or decreasing calcifications. Close imaging is a key follow-up component
in active surveillance.
PMID- 28705687
TI - Antecedents and precipitants of patient-related violence in the emergency
department: Results from the Australian VENT Study (Violence in Emergency Nursing
and Triage).
AB - INTRODUCTION: Workplace violence is one of the most significant and hazardous
issues faced by nurses globally. It is a potentially life-threatening and life
affecting workplace hazard often downplayed as just "part of the job" for nurses.
METHODS: A cross-sectional design was used and data were collected using a
purpose developed survey tool. Surveys were distributed to all members of the
College of Emergency Nurses' Australasia (CENA) in 2010 and 537 eligible
responses were received (RR=51%). RESULTS: Patient-related violence was reported
by 87% of nurses in the last six months. Precipitants and antecedents for
episodes of violence were reported in three categories: nurse-related; patient
related and emergency-department specific factors. Triaging was identified as the
highest risk nursing activity, and the triage area identified as the highest risk
location in the department. Patients who presented with alcohol intoxication,
substance misuse or mental health issues were identified as the groups at
greatest risk for potential violence. DISCUSSION: Patient-related violence was
reported by the majority of emergency nurses surveyed. A number of precipitants
and antecedents perceived to be risk factors by participants were found to be
significant and are unavoidable in the working lives of emergency department
nurses.
PMID- 28705688
TI - Treatment limitations in the era of ECMO.
PMID- 28705689
TI - Physical after-effects in men undergoing prostate biopsy in routine clinical
practice: Results from the PiCTure study.
AB - BACKGROUND: As the incidence of prostate cancer has, until recently, increased in
most developed countries, the rates of prostate biopsies, required for
histological diagnosis, will also have increased. Little is known about the
physical after-effects of prostate biopsy outside randomised control trials. We
investigate reports on the physical effect of prostate biopsy undertaken in men
in routine practice. METHODS: A self-completed questionnaire was given to men
living in the Republic of Ireland (RoI) or Northern Ireland 4 to 6 weeks after
prostate biopsy. Men were asked about whether they experienced specific physical
after-effects postbiopsy (raised temperature/pain/bleeding/erectile
dysfunction/urinary retention) and, if so, their severity and duration, and any
associated health care uses. Binomial and ordinal logistic regression was used to
investigate factors associated with postbiopsy after-effects (presence/absence)
and number of after-effects reported, respectively. RESULTS: Postbiopsy after
effects were common with 88.1% of 335 respondents reporting at least 1 after
effect; 21% reported at least 3. The odds of increasing number of after-effects
was over 2-fold in men with both intermediate (odds ratio [OR] = 2.59, 95% CI:
1.52-4.42) and high (OR = 2.52, 95% CI: 1.28-4.94) levels of health anxiety and
for men who had had multiple previous biopsies (adjusted OR = 2.02, 95% CI: 1.20
3.41). A total of 21.3% of men who experienced after-effects reported that they
were worse than expected, 11.5% with after-effects reported contacting their
doctor or local pharmacy, 14.6% contacted hospital services, and 3.1% of men with
after-effects were admitted to hospital with an average stay of 5.4 nights
(standard deviation = 6.3). CONCLUSION: Physical after-effects following prostate
biopsy in routine practice are common, and in some men, serious enough to warrant
contacting hospital or community services. Men with increased health anxiety or
who undergo multiple biopsies might benefit from additional support.
PMID- 28705690
TI - Color weight photometry.
AB - We study the "color weight" for a number of rather different paradigms. In well
researched heterochromatic photometry methods we find that the "weights"
determined by settings of naive observers are closely determined by the CIE
luminance functional. This is very different for tasks that involve mid- and high
level aspects of perception. In several cases we find equipollence for the
display red, green and blue channels. Moreover, in such cases the very nonlinear
maximum-rule fits the data rather better than a linear functional. These findings
are of interest when photometry needs to be applied for stimuli that are
different from the high temporal and low spatial frequency gratings typical for
flicker photometry. These results are relevant for science, ergonomics and art.
PMID- 28705691
TI - Functional connectivity within and between intrinsic brain networks correlates
with trait mind wandering.
AB - Individual differences across a variety of cognitive processes are functionally
associated with individual differences in intrinsic networks such as the default
mode network (DMN). The extent to which these networks correlate or anticorrelate
has been associated with performance in a variety of circumstances. Despite the
established role of the DMN in mind wandering processes, little research has
investigated how large-scale brain networks at rest relate to mind wandering
tendencies outside the laboratory. Here we examine the extent to which the DMN,
along with the dorsal attention network (DAN) and frontoparietal control network
(FPCN) correlate with the tendency to mind wander in daily life. Participants
completed the Mind Wandering Questionnaire and a 5-min resting state fMRI scan.
In addition, participants completed measures of executive function, fluid
intelligence, and creativity. We observed significant positive correlations
between trait mind wandering and 1) increased DMN connectivity at rest and 2)
increased connectivity between the DMN and FPCN at rest. Lastly, we found
significant positive correlations between trait mind wandering and fluid
intelligence (Ravens) and creativity (Remote Associates Task). We interpret these
findings within the context of current theories of mind wandering and executive
function and discuss the possibility that certain instances of mind wandering may
not be inherently harmful. Due to the controversial nature of global signal
regression (GSReg) in functional connectivity analyses, we performed our analyses
with and without GSReg and contrast the results from each set of analyses.
PMID- 28705692
TI - How Early do Social Determinants of Health Begin to Operate? Results From the
Fragile Families and Child Wellbeing Study.
AB - PURPOSE: From a life course perspective, important insights about how social
determinants of health operate can be gained by analyzing the various forms that
social climate can take in different life periods. For children, a critical
aspect of social climate is exposure to bullying. Bullying can serve as a proxy
for power imbalance and social exclusion analogous to adult social climate of
discrimination and racism. DESIGN AND METHODS: We used the Year 9 follow-up data
of the Fragile Families and Child Wellbeing Study (N=3301) that, for the first
time included interviews with the children. We drew on a national sample of
children and their families, which allowed us to account for broader contextual
variables and represented a broad range of geographic areas and schools.
Multinomial logistic regression was used to estimate the effects of exposure to
bullying on self-rated health among primarily 9- to 10-year-old children while
controlling for socio-demographic and diagnosed health-conditions. RESULTS: Both
frequency and forms of bullying were positively associated with lower odds of
reporting excellent, very good or good health. The effect of forms of bullying on
children's self-rated health fell on a gradient. Subgroup analysis indicated a
significant effect on self-rated health for children who experienced peer
rejection but not for those who experienced physical aggression. CONCLUSIONS: The
results of the study provide new evidence that the harmful health consequences of
power imbalance and discriminatory practices may extend to children in early
development. It also accentuates the need to study social determinants of health
from both an ecological/contextual and a developmental angle. PRACTICE
IMPLICATIONS: Echoing a plethora of nursing literature on the critical role of
psycho-social pediatric care, this study further encourages pediatric nurses to
expand their assessment and intervention priorities beyond a familial and
developmental perspective, and to consider the evident physical health
consequence of a child's overall social climate determinants.
PMID- 28705693
TI - Erratum to "Clinical outcome of reverse total shoulder arthroplasty combined with
latissimus dorsi transfer for the treatment of chronic combined pseudoparesis of
elevation and external rotation of the shoulder" [J Shoulder Elbow Surg
2014;23:49-57].
PMID- 28705694
TI - Rotator cuff bridging repair using acellular dermal matrix in large to massive
rotator cuff tears: histologic and clinical analysis.
AB - BACKGROUND: This study investigated the efficacy of the bridging repair using an
acellular dermal matrix (ADM) and an ADM with stem cells in rabbits. Also
investigated were clinical outcomes of ADM bridging repair for large to massive
rotator cuff tears. MATERIALS AND METHODS: ADM, with and without stem cells, was
used to cover a 5- * 5-mm-sized cuff defect in 17 rabbits, and biomechanical,
histologic, and immunohistochemical analyses were conducted. Also evaluated were
24 patients with large to massive rotator cuff tears after ADM bridging repair.
RESULTS: In the biomechanical test, the normal rotator cuff, cuff with ADM plus
stem cells, and cuff with ADM in the rabbit model showed a maximum load (N) of
287.3, 217.5, and 170.3 and ultimate tensile strength (N/mm2) of 11.1, 8.0, and
5.2, respectively. Histologically, the cuff tendons with the ADM or ADM plus stem
cells showed characteristically mature tendons as time passed. In the clinical
study, the mean American Shoulder and Elbow Surgeons score improved from
preoperative 50 to postoperative 83, the University of California Los Angeles
Shoulder Rating Scale from 17 to 30, and the Simple Shoulder Test from 4 to 8,
respectively. No further fatty deteriorations or muscle atrophy were observed on
follow-up magnetic resonance imaging. A retear was found in 5 of 24 patients
(21%). CONCLUSIONS: Bridging repair with ADM or stem cells in the rabbit model
showed cellular infiltration into the graft and some evidence of neotendon
formation. Clinically, ADM repair was a safe alternative that did not show any
further fatty deterioration nor muscle atrophy in large to massive rotator cuff
tears.
PMID- 28705695
TI - Modeling extracellular fields for a three-dimensional network of cells using
NEURON.
AB - BACKGROUND: Computational modeling of biological cells usually ignores their
extracellular fields, assuming them to be inconsequential. Though such an
assumption might be justified in certain cases, it is debatable for networks of
tightly packed cells, such as in the central nervous system and the syncytial
tissues of cardiac and smooth muscle. NEW METHOD: In the present work, we
demonstrate a technique to couple the extracellular fields of individual cells
within the NEURON simulation environment. The existing features of the simulator
are extended by explicitly defining current balance equations, resulting in the
coupling of the extracellular fields of adjacent cells. RESULTS: With this
technique, we achieved continuity of extracellular space for a network model,
thereby allowing the exploration of extracellular interactions computationally.
Using a three-dimensional network model, passive and active electrical properties
were evaluated under varying levels of extracellular volumes. Simultaneous
intracellular and extracellular recordings for synaptic and action potentials
were analyzed, and the potential of ephaptic transmission towards functional
coupling of cells was explored. COMPARISON WITH EXISTING METHOD(S): We have
implemented a true bi-domain representation of a network of cells, with the
extracellular domain being continuous throughout the entire model. This has
hitherto not been achieved using NEURON, or other compartmental modeling
platforms. CONCLUSIONS: We have demonstrated the coupling of the extracellular
field of every cell in a three-dimensional model to obtain a continuous uniform
extracellular space. This technique provides a framework for the investigation of
interactions in tightly packed networks of cells via their extracellular fields.
PMID- 28705696
TI - Muscle grip strength is associated to reduced pulmonary capacity in patients with
diabetes.
AB - AIM: This study investigates the role of muscle strength as a predictive factor
for reduced pulmonary function in diabetes. METHODS: Data from the NHANES 2011
2012 were analyzed. Lung function was assessed with spirometry (FEV1, FVC).
Diabetes was assessed with an oral glucose tolerance test (OGTT), glycated
hemoglobin (HbA1c), or fasting plasma glucose (FPG). Muscle strength was measured
by a grip test using a handgrip dynamometer. RESULTS: A total of 3521 people were
suitable to be included for analysis in this study. Lung function was reduced in
diabetes-after adjustment for covariates, the impact of diabetes on FVC was
estimated as -331mL (SE 48) for known diabetes and -282mL (SE 41) for undiagnosed
diabetes (P<0.001). Grip strength was also reduced in diabetes. After adjustment
for covariates, the impact of diabetes was estimated as -5.9kg (SE 0.8) for known
diabetes (P<0.001). An association between lung capacity and grip strength in
people with known diabetes was observed (R=0.7, P<0.001). The adjusted impact on
FVC from grip strength was estimated as 13.1mL (SE 3.4) per kg (P<0.001).
CONCLUSIONS: Muscle strength appears to be reduced in people with known diabetes,
and this seems to affect the respiratory muscles as an independent factor.
PMID- 28705697
TI - Overcoming clinical inertia in insulin initiation in primary care for patients
with type 2 diabetes: 24-month follow-up of the Stepping Up cluster randomised
controlled trial.
AB - AIM: To examine the two-year impact of Stepping Up, a general practice based
model of care intervention for insulin initiation and titration in Australia.
METHODS: 266 participants from 74 general practices participated in the Stepping
Up cluster randomised controlled trial between 2012-2014. Control practices
received training in the model of care on completion of the 12-month trial.
Patients were followed for 24 months. Participant baseline characteristics,
insulin and non-insulin medication use were summarised for each study group.
Linear mixed-effects models with random intercepts were used to estimate
differences in mean outcome (HbA1c and weight) between the study groups using
restricted maximum likelihood estimation. RESULTS: At baseline 61% of patients
were male, mean (SD) age 62 (10) years, diabetes duration 9 (5, 13) years and
mean (95% CI) HbA1c was 8.9 (8.8-9.1)% (74 (73-76)mmol/mol) for both groups.
There was a significant between group difference at 6 months which was sustained
at 24 months; Mean (95% CI) HbA1c at 24 months in the intervention group was 7.6
(7.5-7.8)% (60 (58-62)mmol/mol) and 8.0 (7.7-8.4)% (64 (61-68)mmol/mol) in the
control group. At 24 months 97 (71.3%) of the intervention group and 26 (31.0%)
of the control group were prescribed insulin; there was no significant difference
in weight. Use of non-insulin anti-hyperglycaemic agents was similar in both
groups with the exception of dipeptidyl peptidase-4 inhibitors which were
prescribed more frequently in the control group (30(36%) vs 21(16%)). CONCLUSION:
Stepping Up was associated with improved glycaemic control compared to usual care
for 24 months, suggesting that the model facilitated more timely treatment
intensification. Ongoing RN-CDE support may be needed to facilitate ongoing
treatment intensification.
PMID- 28705698
TI - Receptor activity-modifying protein dependent and independent activation
mechanisms in the coupling of calcitonin gene-related peptide and adrenomedullin
receptors to Gs.
AB - Calcitonin gene-related peptide (CGRP) or adrenomedullin (AM) receptors are
heteromers of the calcitonin receptor-like receptor (CLR), a class B G protein
coupled receptor, and one of three receptor activity-modifying proteins (RAMPs).
How CGRP and AM activate CLR and how this process is modulated by RAMPs is
unclear. We have defined how CGRP and AM induce Gs-coupling in CLR-RAMP
heteromers by measuring the effect of targeted mutagenesis in the CLR
transmembrane domain on cAMP production, modeling the active state conformations
of CGRP and AM receptors in complex with the Gs C-terminus and conducting
molecular dynamics simulations in an explicitly hydrated lipidic bilayer. The
largest effects on receptor signaling were seen with H295A5.40b, I298A5.43b,
L302A5.47b, N305A5.50b, L345A6.49b and E348A6.52b, F349A6.53b and H374A7.47b
(class B numbering in superscript). Many of these residues are likely to form
part of a group in close proximity to the peptide binding site and link to a
network of hydrophilic and hydrophobic residues, which undergo rearrangements to
facilitate Gs binding. Residues closer to the extracellular loops displayed more
pronounced RAMP or ligand-dependent effects. Mutation of H3747.47b to alanine
increased AM potency 100-fold in the CGRP receptor. The molecular dynamics
simulation showed that TM5 and TM6 pivoted around TM3. The data suggest that
hydrophobic interactions are more important for CLR activation than other class B
GPCRs, providing new insights into the mechanisms of activation of this class of
receptor. Furthermore the data may aid in the understanding of how RAMPs modulate
the signaling of other class B GPCRs.
PMID- 28705699
TI - Posterolateral Trajectories Favor a Longer Motor Domain in Subthalamic Nucleus
Deep Brain Stimulation for Parkinson Disease.
AB - OBJECTIVE: The clinical outcome of patients with Parkinson disease (PD) who
undergo subthalamic nucleus (STN) deep brain stimulation (DBS) is, in part,
determined by the length of the electrode trajectory through the motor STN
domain, the dorsolateral oscillatory region (DLOR). Trajectory length has been
found to correlate with the stimulation-related improvement in patients' motor
function (estimated by part III of the United Parkinson's Disease Rating Scale
[UPDRS]). Therefore, it seems that ideally trajectories should have maximal DLOR
length. METHODS: We retrospectively studied the influence of various anatomic
aspects of the brains of patients with PD and the geometry of trajectories
planned on the length of the DLOR and STN recorded during DBS surgery. We
examined 212 trajectories and 424 microelectrode recording tracks in 115 patients
operated on in our center between 2010 and 2015. RESULTS: We found a strong
correlation between the length of the recorded DLOR and STN. Trajectories that
were more lateral and/or posterior in orientation had a longer STN and DLOR pass,
although the DLOR/STN fraction length remained constant. The STN target was more
lateral when the third ventricle was wider, and the latter correlated with older
age and male gender. CONCLUSIONS: Trajectory angles correlate with the recorded
STN and DLOR lengths, and should be altered toward a more posterolateral angle in
older patients and atrophied brains to compensate for the changes in STN location
and geometry. These fine adjustments should yield a longer motor domain pass,
thereby improving the patient's predicted outcome.
PMID- 28705700
TI - Incidental Primary Intradural Carcinoid Tumor in a Patient with Lumbar
Radiculopathy.
AB - BACKGROUND: Carcinoid tumors are neuroendocrine neoplasms derived from
enterochromaffin cells. Central nervous system involvement is rare. The reported
cases include metastases to brain or spinal cord, and primary skeletal or
extradural disease resulting in compressive myeloradiculopathy. There are 2
previously reported cases of primary intradural extramedullary carcinoid tumor,
presenting with compressive symptoms. We report the first case of primary
incidental intradural extramedullary carcinoid tumor. CASE DESCRIPTION: A 68-year
old man was complaining of a 2-month history of left-sided back pain and
sciatica; however, he presented with acutely worse symptoms of severe left
sciatica. There was no sphincter dysfunction nor power deficit on examination. A
magnetic resonance imaging (MRI) scan of the lumbar spine revealed an L4-5
central disk protrusion causing left L5 nerve root compression, and a
heterogeneous enhancing intradural mass at the L2-3 level displacing the cauda
equina. An L4-5 microdiscectomy followed by an L2-3 laminectomy and resection of
the intradural mass was performed. There was a postoperative left S1 paresthesia
that was managed medically; however, the postoperative period was unremarkable. A
postoperative MRI of the lumbar spine showed complete resection of the mass. A
staging scan revealed an incidental thyroid nodule; however, there was no other
disease burden. Histopathology of the resected specimen revealed a primary spinal
carcinoid tumor. CONCLUSIONS: To our knowledge, this is the first reported case
of incidental primary intradural spinal carcinoid tumor. Even though intradural
spinal carcinoid tumors are exceedingly rare, they should be included in the
differential diagnosis of enhancing intradural lesions.
PMID- 28705701
TI - Piezosurgery in Modified Pterional Orbital Decompression Surgery in Graves
Disease.
AB - OBJECTIVE: Piezosurgery uses microvibrations to selectively cut bone, preserving
the adjacent soft tissue. The present study evaluated the use of piezosurgery for
bone removal in orbital decompression surgery in Graves disease via a modified
pterional approach. METHODS: A piezosurgical device (Piezosurgery medical) was
used in 14 patients (20 orbits) with Graves disease who underwent orbital
decompression surgery in additional to drills and rongeurs for bone removal of
the lateral orbital wall and orbital roof. The practicability, benefits, and
drawbacks of this technique in orbital decompression surgery were recorded.
Piezosurgery was evaluated with respect to safety, preciseness of bone cutting,
and preservation of the adjacent dura and periorbita. Preoperative and
postoperative clinical outcome data were assessed. RESULTS: The orbital
decompression surgery was successful in all 20 orbits, with good clinical
outcomes and no postoperative complications. Piezosurgery proved to be a safe
tool, allowing selective bone cutting with no damage to the surrounding soft
tissue structures. However, there were disadvantages concerning the
intraoperative handling in the narrow space and the efficiency of bone removal
was limited in the orbital decompression surgery compared with drills.
CONCLUSIONS: Piezosurgery proved to be a useful tool in bone removal for orbital
decompression in Graves disease. It is safe and easy to perform, without any
danger of damage to adjacent tissue because of its selective bone-cutting
properties. Nonetheless, further development of the device is necessary to
overcome the disadvantages in intraoperative handling and the reduced bone
removal rate.
PMID- 28705702
TI - Recurrent Pituicytoma with Pseudoaneurysm: Report of a Challenging Case.
AB - BACKGROUND: Pituicytoma is a rare tumor originating from glial cells of the adult
neurohypophysis and infundibulum. Surgical removal is the treatment of choice for
this neoplasm. In recent years the endoscopic endonasal approach has proven to be
a viable and effective alternative to standard craniotomy. CASE DESCRIPTION: We
report a case of a patient submitted to surgical treatment for a recurrence of
pituicytoma, which was operated on transcranially at another hospital
approximately 5 years previously. After transcranial surgery, the patient
developed a symptomatic recurrence and an undisclosed intrasellar pseudoaneurysm
that were treated with an endoscopic endonasal approach, but still required an
intracranial approach to complete the resection. CONCLUSIONS: An intrasellar
pseudoaneurysm can endanger the endoscopic removal of the pituicytoma, forcing
the surgeon to reevaluate a microscopic transcranial approach or to consider a
staged procedure.
PMID- 28705703
TI - A Technique for Resecting Occipital Pole Gliomas Using a Keyhole Lobectomy.
AB - OBJECTIVE: Our purpose is to describe a method of resecting occipital pole
gliomas through a keyhole lobectomy and share the patient outcomes of this
technique. METHODS: We performed a retrospective review of data obtained on all
patients who underwent resection of occipital pole gliomas by the senior author
between 2012 and 2016. We describe our technique for resecting these tumors using
a keyhole lobectomy and share the patient outcomes of this operation. RESULTS:
Eight patients were included in this study. Four patients (50%) had not received
previous surgery. One patient (13%) was diagnosed with a World Health
Organization grade II tumor, and 7 patients (88%) were diagnosed with
glioblastoma. Two tumors (25%) were left sided and 6 (75%) right sided. The
median size of resection was 28 cm3. The median extent of resection was 96%, and
at least 90% of the tumor was resected in all cases. None of the patients
experienced permanent postoperative complications. Temporary neurologic
complications included 3 patients (38%) with encephalopathy and 1 patient (13%)
with aphasia. There were no neurosurgical complications. CONCLUSIONS: Our study
provides details on the technical aspects of occipital keyhole lobectomies and
gives the outcomes of patients who have received an operation for tumors in this
uncommon location. Taking white matter tract anatomy into consideration, we show
that the keyhole method can be applied to gliomas of the occipital lobe.
PMID- 28705704
TI - Effects of Preoperative Simulation on Minimally Invasive Hybrid Lumbar Interbody
Fusion.
AB - OBJECTIVE: The main focus of this study was to evaluate how preoperative
simulation affects the surgical work flow, radiation exposure, and outcome of
minimally invasive hybrid lumbar interbody fusion (MIS-HLIF). METHODS: A total of
132 patients who underwent single-level MIS-HLIF were enrolled in a cohort study
design. Dose area product was analyzed in addition to surgical data. Once
preoperative simulation was established, 66 cases (SIM cohort) were compared with
66 patients who had previously undergone MIS-HLIF without preoperative simulation
(NO-SIM cohort). RESULTS: Dose area product was reduced considerably in the SIM
cohort (320 cGy.cm2 NO-SIM cohort: 470 cGy.cm2; P < 0.01). Surgical time was
shorter for the SIM cohort (155 minutes; NO-SIM cohort, 182 minutes; P < 0.05).
SIM cohort had a better outcome in Numeric Rating Scale back at 6 months follow
up compared with the NO-SIM cohort (P < 0.05). CONCLUSIONS: Preoperative
simulation reduced radiation exposure and resulted in less back pain at the 6
months follow-up time point. Preoperative simulation provided guidance in
determining the correct cage height. Outcome controls enabled the surgeon to
improve the procedure and the software algorithm.
PMID- 28705705
TI - Did the Romans die of antimony poisoning? The case of a Pompeii water pipe (79
CE).
PMID- 28705706
TI - Inflammatory myofibroblastic tumors of the lung carrying a chimeric A2M-ALK gene:
report of 2 infantile cases and review of the differential diagnosis of infantile
pulmonary lesions.
AB - We report 2 infantile cases of pulmonary tumor carrying a chimeric A2M-ALK gene.
A2M-ALK is a newly identified anaplastic lymphoma kinase (ALK)-related chimeric
gene from a tumor diagnosed as fetal lung interstitial tumor (FLIT). FLIT is a
recently recognized infantile pulmonary lesion defined as a mass-like lesion that
morphologically resembles the fetal lung. Grossly, FLIT characteristically
appears as a well-circumscribed spongy mass, whereas the tumors in these patients
were solid and firm. Histologically, the tumors showed intrapulmonary lesions
composed of densely proliferating polygonal or spindle-shaped mesenchymal cells
with diffuse and dense infiltrations of inflammatory cells forming microcystic or
micropapillary structures lined by thyroid transcription factor 1-positive
pneumocytes, favoring inflammatory myofibroblastic tumor rather than FLIT. The
proliferating cells were immunoreactive for ALK, and A2M-ALK was identified in
both tumors with reverse-transcription polymerase chain reaction. The dense
infiltration of inflammatory cells, immunoreactivity for ALK, and identification
of an ALK-related chimeric gene suggested a diagnosis of inflammatory
myofibroblastic tumor. Histologically, most reported FLITs show sparse
inflammatory infiltrates and a relatively low density of interstitial cells in
the septa, although prominent infiltration of inflammatory cells and high
cellularity of interstitial cells are seen in some FLITs. The present cases
suggest that ALK rearrangements, including the chimeric A2M-ALK gene, may be
present in these infantile pulmonary lesions, especially those with inflammatory
cell infiltration. We propose that these infantile pulmonary lesions containing a
chimeric A2M-ALK gene be categorized as a specific type of inflammatory
myofibroblastic tumor that develops exclusively in neonates and infants.
PMID- 28705707
TI - GATA3 as a valuable marker to distinguish clear cell papillary renal cell
carcinomas from morphologic mimics.
AB - Clear cell papillary renal cell carcinoma (CCPRCC) is a low-grade, indolent
neoplasm with no reported cases of death from disease or metastasis. These
lesions can show clinical, morphologic, and immunophenotypic overlap with several
aggressive forms of renal cell carcinoma (RCC), including clear cell RCC,
translocation RCC, and papillary RCC with cytoplasmic clearing. Given the
difference in behavior, it is important to reliably separate these entities. We
retrospectively reviewed 47 tumors from 45 patients with morphologic features of
CCPRCC. All cases were stained against cytokeratin 7 (CK7), carbonic anhydrase IX
(CAIX), and GATA3. Cases inconsistent with CCPRCC were reclassified. In addition,
we stained tissue microarrays with 103 typical clear cell RCCs and 62 papillary
RCCs, each in triplicate. Twenty-five cases were morphologically and
immunophenotypically consistent with CCPRCC; all of them showed diffuse CK7
expression and cup-like reactivity with CAIX. Of these, 19 (76%) showed strong
nuclear reactivity for GATA3. Although some non-CCPRCC neoplasms showed at least
partial CK7/CAIX coexpression, none were immunopositive for GATA3. All background
normal kidneys studied showed GATA3 expression in the distal tubules, collecting
ducts, and retention cysts of the distal nephron. On follow-up, none of the
patients with CCPRCC had recurrences or metastasis. Sensitivity and specificity
for GATA3 staining in the diagnosis of CCPRCC were 76% and 100%, with positive
and negative predictive values of 100% and 74%. In conclusion, GATA3 is specific
and sensitive for CCPRCC and can be used for accurate distinction from its main
mimickers. Coexpression of GATA3 and CK7 in most CCPRCC provides evidence of
their origin from distal nephron.
PMID- 28705708
TI - Perineural invasion by prostate cancer on MR/US fusion targeted biopsy is
associated with extraprostatic extension and early biochemical recurrence after
radical prostatectomy.
AB - In recent years, multiparametric magnetic resonance imaging and magnetic
resonance/ultrasound fusion targeted biopsy (TB) have become more widely adopted
to aid in prostate cancer (PCa) detection. Previously, TB has been found to
increase the yield of clinically significant PCa and is more likely to sample the
index tumor compared with traditional 12-core extended sextant biopsies.
Currently, the prognostic significance of perineural invasion (PNI) when
identified on TB (PNI-TB) is unknown. We identified 95 men at 2 tertiary referral
centers who underwent TB followed by radical prostatectomy between January 2014
and January 2017. Clinical, radiological, and pathological variables were
retrospectively reviewed. PNI was identified on TB in 27 of 95 (28.4%) patients.
On multivariable logistic regression, independent predictors of extraprostatic
extension were prostate-specific antigen, TB maximum % core involvement, and PNI
TB (all P<.05). Furthermore, Kaplan-Meier analysis demonstrated that PNI-TB was
associated with early biochemical recurrence events within 12 months after
prostatectomy (log-rank P=.049). Given the increasing adoption of TB for PCa
detection in clinical practice, PNI-TB may be useful for PCa risk stratification.
PMID- 28705709
TI - A novel sclerosing atypical lipomatous tumor/well-differentiated liposarcoma in a
7-year-old girl: report of a case with molecular confirmation.
AB - Atypical lipomatous tumor (ALT)/well-differentiated liposarcoma
(WDL)/dedifferentiated liposarcoma (DDL) is a common type of liposarcoma in late
adulthood. However, pediatric ALT/WDL/DDL is extremely rare, and only 3 cases
have been described in children younger than 10 years of age. Notably, none of
these cases harbored MDM2 gene amplification. Here, we reported a sclerosing
ALT/WDL in a 7-year-old Chinese girl. Histologically, in most areas, the
neoplastic cells were embedded within the collagenous background, and typical
lipogenic areas were inconspicuous throughout the sclerotic areas. In addition,
scattered small foci of atypical osseous/chondrous elements were identified.
Notably, a small typical lipoma-like ALT/WDL area was detected in the periphery
of the mass. Immunohistochemically, all the neoplastic components demonstrated
positivity for MDM2, CDK4, and p16. Fluorescence in situ hybridization revealed
MDM2 gene amplification in all the tumor components. To the best of our
knowledge, this is the first example of MDM2-amplified ALT/WDL in this age group.
PMID- 28705710
TI - Using p16 immunohistochemistry to classify morphologic cervical intraepithelial
neoplasia 2: correlation of ambiguous staining patterns with HPV subtypes and
clinical outcome.
AB - p16INK4a immunohistochemistry (IHC) is widely used to facilitate the diagnosis of
human papillomavirus (HPV)-associated cervical precancerous lesions. Although
most p16 results are distinctly positive or negative, certain ones are ambiguous:
they meet some but not all requirements for the "block-positive" pattern. It is
unclear whether ambiguous p16 immunoreactivity indicates oncogenic HPV infection
or risk of progression. Herein, we compared HPV genotypes and subsequent high
grade squamous intraepithelial lesion (HSIL) outcomes among 220 cervical biopsies
with a differential diagnosis of cervical intraepithelial neoplasia 2 based on
hematoxylin and eosin morphology and varying degrees of p16 immunoreactivity. p16
results were classified as block positive (n=40, 18%), negative (n=130, 59%), or
ambiguous (n=50, 23%), a category we further grouped into 3 patterns:
strong/basal (n=18), strong/focal (n=15), and weak/diffuse (n=17). Seventy
percent of ambiguous p16 lesions were negative for the most common low- and high
risk HPV types; the remaining 30% were positive for HPV 16, 18, 45, 58, 59, or
66. Three patterns revealed comparably low HPV detection rates (28%, 27%, and
35%). During 12-month surveillance, HSILs were detected in 35% of the p16 block
positive group, 1.5% of negative group, and 16% of the ambiguous group. The
accuracy of ambiguous p16 immunoreactivity in predicting oncogenic HPV and HSIL
outcome is significantly lower than that of the block-positive pattern but
greater than negative staining. Specific guidelines for this intermediate
category should prevent diagnostic errors and help implement p16 IHC in general
practice.
PMID- 28705711
TI - Asymptomatic Bilateral Central Pulmonary Embolism Following Multiple Cement
Vertebroplasties.
PMID- 28705712
TI - Hydrolysis of diadenosine polyphosphates. Exploration of an additional role of
Mycobacterium smegmatis MutT1.
AB - Diadenosine polyphosphates (ApnA, n=2-6), particularly Ap4A, are involved in
several important physiological processes. The substantial sequence identity of
the Nudix hydrolase domain (domain 1) of Mycobacterium smegmatis MutT1 (MsMutT1)
with a known Ap4A hydrolase suggested that MsMutT1 could also hydrolyse
diadenosine polyphosphates. Biochemical experiments yielded results in conformity
with this suggestion, with Ap4A as the best among the substrates. ATP is a
product in all experiments; small amounts of ADP were also observed in the
experiments involving Ap4A and Ap6A. Hydrolysis was inhibited by fluoride ions in
all cases. The mechanism of action and its inhibition in relation to ApnA were
explored through the X-ray analysis of the crystals of the MsMutT1 complexes with
Ap5A; Ap5A and MnCl2; Ap4A; ATP; and ATP.NaF.MgCl2. The aggregation pattern of
molecules in the first four crystals is similar to that found in a majority of
MsMutT1-NTP crystals. Substrate molecules occupy the primary binding site and ATP
occupies a site at an intermolecular interface, in the first two. ATP occupies
both the sites in the third and fourth crystal. The protein-ligand interactions
observed in these crystal structures lead to an explanation of the molecular
mechanism of hydrolysis of ApnA by MsMutT1. The fifth crystal exhibits a new
packing arrangement. The structure of the complex provides an explanation for the
fluoride inhibition of the activity of the enzyme. It would thus appear that
MutT1 has a major role involving the hydrolysis of diadenosine polyphosphates,
which could be elucidated at the molecular level.
PMID- 28705713
TI - SN003, a CRF1 receptor antagonist, attenuates depressive-like behavior and
detrusor overactivity symptoms induced by 13-cis-retinoic acid in rats.
AB - Overactive bladder (OAB) often co-exists with depression in women. The
corticotropin-releasing factor (CRF) system participates in the pathophysiology
of both disorders. Therefore, we tested the effects of acute treatment with a
reversible CRF receptor type-1 (CRF1) antagonist, SN003 (1mg/kg, i.v.),
representatives of first (solifenacin, 0.03mg/kg, i.v.) and second (mirabegron,
1mg/kg, i.v.) line treatments for OAB as well as an antidepressant imipramine
(30mg/kg, i.p.) on changes in depressive-like behavior and detrusor overactivity
(DO) symptoms induced by a 6-week administration of 13-cis-retinoic acid (13-cis
RA, 1mg/kg/day, i.p.) in female Wistar rats, using in vivo cystometric
investigations, forced swim test (FST) and spontaneous locomotor activity test.
Following cystometric and behavioral studies, tissue was harvested and CRF level
was assessed in the hypothalamus, amygdala and plasma. 13-cis-RA-induced
depressive-like behavior and DO symptoms were associated with increased CRF
levels in the hypothalamus, amygdala and plasma. Solifenacin and mirabegron
attenuated DO symptoms induced by 13-cis-RA, did not display antidepressant-like
activity and did not influence CRF levels in brain tissues or plasma. Imipramine
and SN003 displayed antidepressant-like activity and lowered increased levels of
CRF in brain tissues and plasma. Imipramine attenuated changes in some of the
cystometric parameters, which are associated with OAB dry (without urge
incontinence), whereas SN003 attenuated changes in almost all cystometric
parameters that were induced by 13-cis-RA. CRF1 antagonist may be beneficial in
case of OAB wet (with urge incontinence) or dry co-existing with depression. The
possible mechanism may be related to the effects on central/peripheral CRF
system.
PMID- 28705714
TI - Aristeromycin and DZNeP cause growth inhibition of prostate cancer via induction
of mir-26a.
AB - Most prostate cancers initially respond to androgen deprivation therapy, but then
progress from androgen-dependent to androgen-independent prostate cancers. In the
present study, a differential cytotoxicity screen of hormone-resistant prostate
cancer LNCaP-hr cells and the parental LNCaP-FGC cells against normal MRC5
fibroblast cells, identified a small molecule compound, Aristeromycin (a
derivative of 3-deazaneplanocin A (DZNeP)). The molecular target was shown to be
S-adenosylhomocysteine hydrolase (AHCY), which catalyzes reversible hydrolysis of
S-adenosylhomocysteine (SAH) to adenosine and L-homocysteine. DZNeP and
Aristeromycin showed high inhibitory activity against AHCY. Treatment of the
prostate cancer cells with DZNeP led to SAH accumulation and decreased levels of
homocysteine and histone H3K27 methylation. SAH accumulation and cell growth
inhibition were confirmed after siRNA-mediated AHCY knockdown. To further
understand why AHCY inhibitors decreased prostate cancer cell growth, we
performed microRNA expression profiling with LNCaP-hr cells. Mir-26a, which is
involved in regulation of EZH2 expression, was upregulated in Aristeromycin
treated LNCaP-hr cells. A reporter assay established with the EZH2 3'-UTR
confirmed that transfection of microRNA precursor molecules for miR-26a decreased
the EZH2 3'-UTR luciferase activity. Meanwhile, an antisense microRNA inhibitor
for miR-26a recovered the luciferase activity. The present findings suggest, at
least in part, that miR-26a induced by an AHCY inhibitor can regulate oncogenic
EZH2 expression, and could thus be an important mechanism of action for AHCY
inhibitors in the treatment of prostate cancer.
PMID- 28705715
TI - Acute treatment with doxorubicin affects glutamate neurotransmission in the mouse
frontal cortex and hippocampus.
AB - Doxorubicin (DOX) is a potent chemotherapeutic agent known to cause acute and
long-term cognitive impairments in cancer patients. Cognitive function is
presumed to be primarily mediated by neuronal circuitry in the frontal cortex
(FC) and hippocampus, where glutamate is the primary excitatory neurotransmitter.
Mice treated with DOX (25mg/kg i.p.) were subjected to in vivo recordings under
urethane anesthesia at 24h post-DOX injection or 5 consecutive days of cognitive
testing (Morris Water Maze; MWM). Using novel glutamate-selective microelectrode
arrays, amperometric recordings measured parameters of extracellular glutamate
clearance and potassium-evoked release of glutamate within the medial FC and
dentate gyrus (DG) of the hippocampus. By 24h post-DOX injection, glutamate
uptake was 45% slower in the FC in comparison to saline-treated mice. In the DG,
glutamate took 48% longer to clear than saline-treated mice. Glutamate overflow
in the FC was similar between treatment groups, however, it was significantly
increased in the DG of DOX treated mice. MWM data indicated that a single dose of
DOX impaired swim speed without impacting total length traveled. These data
indicate that systemic DOX treatment changes glutamate neurotransmission in key
nuclei associated with cognitive function within 24h, without a lasting impact on
spatial learning and memory. Understanding the functional effects of DOX on
glutamate neurotransmission may help us understand and prevent some of the
debilitating side effects of chemotherapeutic treatment in cancer survivors.
PMID- 28705716
TI - Occult hepatitis B virus infection in Greek patients with congenital bleeding
disorders.
AB - Occult Hepatitis B Infection (OBI) is a form of chronic HBV infection
characterized by low level HBV DNA, without detectable HBV surface antigen
(HBsAg). OBI is frequently associated with the presence of anti-HBc and in some
cases also with anti-HBs. Patients, who formerly received non-inactivated factor
concentrates, can potentially be considered at high risk for OBI, especially
since these patients usually are HIV or HCV co-infected. This study aimed to
assess the prevalence of occult HBV infection in Greek patients with hereditary
bleeding disorders. The study sample comprised of 114 patients from a single
haemophilia center. All patients were screened for HBV serum markers and
individually tested for HBV DNA using a qualitative PCR. Presence of HBV DNA was
further confirmed by quantification of viral load with an ultrasensitive in-house
real time PCR. 88 and 21 patients with haemophilia A and B, respectively, 4
patients with von Willebrand Disease and 1 patient with severe factor VII
deficiency were screened for the presence of OBI. Anti-HBc were detected in 53
(46.5%) subjects; 18 of them were anti-HBs(-) and 35 anti-HBs(+). Anti-HBe were
present in 26 subjects. Two out of 114 patients were HBsAg(+). Of the remaining
112 HBsAg(-) patients tested, two (1.8%) were found HBsAg(-), HBV DNA(+), anti
HBc(+) and anti-HBs(-) and were identified as potential OBI cases. Both cases
exhibited very low DNA levels; 38.2IU/mL in patient A and 14.2IU/mL in patient B.
Both patients were HBeAg(-), but patient A had HBe antibodies. Patient B was also
HIV/HCV co-infected. In conclusion, two cases of OBI with low HBV viraemia were
identified among patients with congenital bleeding disorders. Although the
incidence in our sample is moderately low (1.8%), close monitoring of these
infections is of great clinical significance, especially in patients with co
infections and concomitant immunosuppression.
PMID- 28705717
TI - Whole-genome characterization of Uruguayan strains of avian infectious bronchitis
virus reveals extensive recombination between the two major South American
lineages.
AB - Infectious bronchitis virus (Gammacoronavirus, Coronaviridae) is a genetically
variable RNA virus that causes one of the most persistent respiratory diseases in
poultry. The virus is classified in genotypes and lineages with different
epidemiological relevance. Two lineages of the GI genotype (11 and 16) have been
widely circulating for decades in South America. GI-11 is an exclusive South
American lineage while the GI-16 lineage is distributed in Asia, Europe and South
America. Here, we obtained the whole genome of two Uruguayan strains of the GI-11
and GI-16 lineages using Illumina high-throughput sequencing. The strains here
sequenced are the first obtained in South America for the infectious bronchitis
virus and provide new insights into the origin, spreading and evolution of viral
variants. The complete genome of the GI-11 and GI-16 strains have 27,621 and
27,638 nucleotides, respectively, and possess the same genomic organization.
Phylogenetic incongruence analysis reveals that both strains have a mosaic genome
that arose by recombination between Euro Asiatic strains of the GI-16 lineage and
ancestral South American GI-11 viruses. The recombination occurred in South
America and produced two viral variants that have retained the full-length S1
sequences of the parental lineages but are extremely similar in the rest of their
genomes. These recombinant virus have been extraordinary successful, persisting
in the continent for several years with a notorious wide geographic distribution.
Our findings reveal a singular viral dynamics and emphasize the importance of
complete genomic characterization to understand the emergence and evolutionary
history of viral variants.
PMID- 28705718
TI - Antimicrobial peptide repertoire of Thitarodes armoricanus, a host species of
Ophiocordyceps sinensis, predicted based on de novo transcriptome sequencing and
analysis.
AB - Ophiocordyceps sinensis is an entomopathogenic fungus that parasitizes the larvae
of ghost moths. The fungus-caterpillar complex resulting from fungal parasitism
is a medicinally and economically important traditional Chinese medicine famous
for its tonic, aphrodisiac and immunomodulatory activity. Antimicrobial peptides
(AMPs), which play predominant roles in responding to infection of pathogenic
microorganisms in the immune system of ghost moths, may remain behind the fungus
caterpillar complex. Thitarodes armoricanus, as a widely distributed ghost moth
on the Tibetan Plateau, is the first reported and one of the most common host
insects of O. sinensis. However, there is little information about AMPs of T.
armoricanus. In this study, high-throughput RNA-seq analysis and transcriptome
assembly and annotation of T. armoricanus was performed to explore the AMP
repertoire. A total of 41,464 unigenes were obtained by de novo assembly, and
20,080 unigenes including 385 immunity-related candidates were annotated. Among
which, 16 AMP nucleotide sequences were identified. Based on their peptide
structure, these were further classified as cecropin, defensin, attacin and
gloverin AMPs. All identified AMPs are highly conserved in the Hepialidae family
with distinct features as in other insect AMPs. In conclusion, this research
offers insights into the AMP repertoire of T. armoricanus which gives opportunity
for the further study of the AMP-related medical components of the fungus
caterpillar complex. The identified AMPs from T. armoricanus also provide
valuable information for a better understanding of the immune mechanism of
Thitarodes and the formation of the mysterious entomo-fungal combination.
PMID- 28705719
TI - Prevalence of EBV, HPV and MMTV in Pakistani breast cancer patients: A possible
etiological role of viruses in breast cancer.
AB - BACKGROUND: Breast cancer being a multifactorial disease, the role of infectious
agent in development of disease is of great interest. The high incidence of
breast cancer around the world has woken the interest in a viral etiology of
breast cancer. Despite decades of research, no etiologic factor(s) for human
breast cancer has been known and the quest for a contributing cause has all but
been abandoned during the past years. Recent investigations have linked breast
cancer to viral infections, such as Epstein-Barr virus (EBV), Human
papillomavirus (HPV) and mouse mammary tumor virus. AIM: To investigate the
possible association of EBV, HPV and MMTV infection with breast cancer
development and progression. METHODS: Screening of isolated genomic DNA from FFPE
breast cancer tissue biopsies (n=250) using standard polymerase chain reaction
and correlation of virus prevalence with BC disease outcomes using statistical
analysis software (SPSS 16.0). RESULTS: Our findings suggest the prevalence of
EBV (24.4%), HPV (18.1%) and MMTV (29.3%), while coinfection of HPV and EBV was
detected in 9.2% (23/250), co infection of HPV and MMTV in 3.2% (8/250) and
coinfection of EBV and MMTV in 6% (15/250) of breast cancer samples. No virus was
detected in 59.5% of the breast cancer samples. Mono infection of EBV and HPV do
not statistically co-relate with the clinico-pathological outcomes of breast
cancer disease, though MMTV infection does co-relate with age and grade of breast
cancer disease. In our study, the prevalence of coinfection of HPV, EBV and MMTV
in Pakistani breast cancer patients is rare, still there is a possibility of
synergistic carcinogenic effect of different viruses in the development of breast
cancer disease. CONCLUSION: The significant percentage of virus prevalence shows
potential role in breast cancer development. However, this study provides
substantial but not conclusive evidence for the involvement of viruses in BC
disease development and progressiveness.
PMID- 28705720
TI - Dietary supplementation with selenium yeast and tea polyphenols improve growth
performance and nitrite tolerance of Wuchang bream (Megalobrama amblycephala).
AB - In order to explore the effects of dietary selenium yeast, tea polyphenols and
their combination on growth of Wuchang bream (Megalobrama amblycephala) and its
resistance to nitrite stress, 360 healthy Wuchang bream with initial body weight
of (55.90 +/- 2.60) g were randomly divided into four groups: a control group fed
with basal diet and three treated groups fed with basal diets supplemented with
0.50 mg/kg selenium yeast, 50 mg/kg tea polyphenols, and the combination of 0.50
mg/kg selenium yeast and 50 mg/kg tea polyphenols, respectively. After 60 d of
feeding, the growth performance of Wuchang bream was measured. Then 25 fish per
tank were exposed to nitrite stress of 15.0 mg/L. The serum stress hormones,
liver histology and hepatic antioxidant responses were evaluated before nitrite
exposure (0 h) and at 6, 12, 24, 48 and 96 h after exposure. The results showed
that before nitrite exposure, compared with the control, the weight gain,
specific growth rate, liver total antioxidant capacity, the activities and
transcriptional levels of hepatic antioxidant enzymes (superoxide dismutase and
glutathione peroxidase) in the selenium yeast and combination groups were
significantly increased, while feed conversion rate was decreased significantly,
which suggested that the combined use of selenium yeast and tea polyphenols as
well as the single selenium yeast supplementation improved growth performance and
enhanced antioxidant capacity in fish. After nitrite exposure, compared with the
control, liver total antioxidant capacity as well as the activities and
transcription levels of catalase superoxide dismutase and glutathione peroxidase
in three treatment groups were significantly increased in varying degrees whereas
serum cortisol contents and liver malondialdehyde levels were decreased
significantly. By contrast, the combined use of selenium yeast and tea
polyphenols was more effective than the single supplementation with selenium
yeast or tea polyphenols. In consistent with this, alterations of the liver
histostructure in three treatment groups were slower and less severe than in the
control group after nitrite exposure. In conclusion, a basal diet supplemented
with the combination of 0.50 mg/kg selenium yeast and 50 mg/kg tea polyphenols
could effectively improve growth performance and nitrite resistance in Wuchang
bream.
PMID- 28705721
TI - Characterization of NLRP3-like gene from Apostichopus japonicus provides new
evidence on inflammation response in invertebrates.
AB - Inflammatory/defensive response after pathogen invasion is considered a local
defense reaction in vertebrates. Inflammation response in Apostichopus japonicus
was hardly determined due to scarce information available for nucleotide binding
domain-like receptor family, pyrin domain-containing (NLRP) family. In the
present study, invertebrate NLRP homologue was identified from A. japonicus
(designated as AjNLRP3-like) by rapid amplification of cDNA ends. Full-length
cDNA of AjNLRP3-like measured 2970 bp with 2265 bp open reading frame encoding a
754-amino acid (aa) residue protein. Structural analysis revealed that AjNLRP3
like processed characteristic domains of pyrin (32-102aa) and NACHT (183-339aa).
Multiple sequence alignment and phylogenetic analysis supported that AjNLRP3-like
belongs to a new member of NLRP3 protein subfamily. Spatial expression analysis
revealed that AjNLRP3-like was ubiquitously expressed in all examined tissues
with larger magnitude in coelomocytes. Both Vibrio splendidus challenge in vivo
and lipopolysaccharide stimulation in vitro significantly upregulated mRNA
expression of AjNLRP3-like when compared with the control group. NLRP3-mediated
inflammation response depended on release of lysosomal cathepsin B (CTSB) and
subsequent activation of high-mobility group box (HMGB) in vertebrates. We
investigated expression profiles of AjNLRP3-like and AjHMGB after AjCTSB knock
down and discovered that AjNLRP3-like was depressed by 0.66-fold and 0.47-fold,
whereas AjHMGB was depressed by 0.70-fold and 0.50-fold at 24 and 48 h in AjCTSB
silenced group, respectively. Similarly, down-regulation of AjHMGB was also
observed after AjNLRP3-like knock-down. This study therefore suggests that A.
japonicus feature similar inflammatory events as those in vertebrates, and
activation of AjNLRP3-like depends on AjCTSB expression and release of AjHMGB.
PMID- 28705722
TI - Identification, characterization and expression analysis of TLR5 in the mucosal
tissues of turbot (Scophthalmus maximus L.) following bacterial challenge.
AB - TLRs (Toll-like receptors) are very important pathogen pattern recognition
receptors, which control the host immune responses against pathogens through
recognition of molecular patterns specific to microorganisms. In this regard,
investigation of the turbot TLRs could help to understand the immune responses
for pathogen recognition. Here, transcripts of two TLR5 (TLR5a and TLR5b) were
captured, and their protein structures were also predicted. Meanwhile, we
characterized their expression patterns with emphasis on mucosal barriers
following different bacterial infection. The phylogenetic analysis revealed the
turbot TLR5 genes showed the closest relationship to Paralichthys olivaceus.
These two TLR5 genes were ubiquitously expressed in healthy tissues although
expression levels varied among the tested tissues. In addition, the two copies of
turbot TLR5 showed different expression patterns after bacterial infections.
After Vibrio anguillarum infection, TLR5a was generally up-regulated in intestine
and skin while down-regulated in gill, while TLR5b showed a general down
regulation in mucosal tissues. After Streptococcus iniae infection, the TLR5a was
down-regulated at 2 h while generally up-regulated after 4 h in mucosal tissues.
Interestingly, the TLR5b was up-regulated in intestine while down-regulated in
skin and gill after Streptococcus iniae infection. These findings suggested a
possible irreplaceable role of TLR5 in the immune responses to the infections of
a broad range of pathogens that include Gram-negative and Gram-positive bacteria.
Future studies should apply the bacteriological and immune-histochemical
techniques to study the main sites on the mucosal tissue for bacteria entry and
identify the ligand specificity of the turbot TLRs after challenge.
PMID- 28705723
TI - A Pacifastacus leniusculus serine protease interacts with WSSV.
AB - Serine proteases are involved in many critical physiological processes including
virus spread and replication. In the present study, we identified a new clip
domain serine protease (PlcSP) in the crayfish Pacifastacus leniusculus
hemocytes, which can interact with the White Spot Syndrome Virus (WSSV) envelope
protein VP28. It was characterized by a classic clip domain with six strictly
conserved Cys residues, and contained the conserved His-Asp-Ser (H-D-S) motif in
the catalytic domain. Furthermore, signal peptide prediction revealed that it has
a 16-residue secretion signal peptide. Tissue distribution showed that it was
mainly located in P. leniusculus hemocytes, and its expression was increased in
hemocytes upon WSSV challenge. In vitro knock down of PlcSP decreased both the
expression of VP28 and the WSSV copy number in hematopoietic stem (HPT) cells.
Accordingly, these data suggest that the new serine protease may be of importance
for WSSV infection into hematopoietic cells.
PMID- 28705724
TI - CHSE-214: A model for studying extracellular dsRNA sensing in vitro.
AB - Double-stranded RNA (dsRNA) is produced by almost all viruses during their
replicative cycle and is a potent inducer of the innate antiviral immune response
including inducing expression of type I interferons (IFNs) and interferon
stimulated genes (ISGs). During lytic virus infections intracellular dsRNA can
escape into the extracellular space, where surface pattern recognition receptors,
such as class A scavenger receptors (SR-As) facilitate its binding and entry into
neighbouring cells. Studying extracellular dsRNA entry is difficult due to the
ubiquitous expression profile and compensatory dsRNA binding characteristics of
SR-As; a SR-A deficient cell line has yet to be identified. The present study
suggests the Chinook salmon embryonic cell line, CHSE-214, as a model for
studying extracellular dsRNA sensing in vitro. CHSE-214 is unable to bind and
respond to extracellular dsRNA, can only respond to dsRNA when it is transfected
into the cells, and is able to bind dsRNA when overexpressing human SR-AI. The
applications for this model could include elucidating: dsRNA binding and entry
mechanisms, including sequence and length effects, as well as SR-A and other
putative surface dsRNA receptor ligand binding studies.
PMID- 28705725
TI - Assessing the impact of protein extraction methods for human gut metaproteomics.
AB - : Metaproteomics is a promising methodology for the functional characterizations
of the gut microbiome. However, the performance of metaproteomic analysis is
affected by protein extraction protocols in terms of the amount of protein
recovered and the relative abundance of different bacteria observed in
microbiome. Currently, there is a lack of consistency on protein extraction
methods in published metaproteomics studies. Here we evaluated the effects of
different protein extraction methods on human fecal metaproteome
characterizations. We found that sodium dodecyl sulfate (SDS)-based lysis buffer
obtained higher protein yields and peptide/protein group identifications compared
to urea and the non-ionic detergent-based B-Per buffer. The addition of bead
beating to any of the extraction buffers increased both protein yields and
protein identifications. As well, bead beating led to a significant increase of
the relative abundances of Firmicutes and Actinobacteria. We also demonstrated
that ultrasonication, another commonly used mechanical disruption approach,
performed even better than bead beating for gut microbial protein extractions.
Importantly, proteins of the basic metabolic pathways showed significantly higher
relative abundances when using ultrasonication. Overall, these results
demonstrate that protein extraction protocols markedly impact the metaproteomic
results and recommend a protein extraction protocol with both SDS and
ultrasonication for metaproteomic studies. BIOLOGICAL SIGNIFICANCE: The gut
microbiome is emerging as an important factor influencing human health.
Metaproteomics is promising for advancing the understanding of the functional
roles of the microbiome in disease. However, metaproteomics suffers from a lack
of consistent sample preparation procedures. In the present study, protein
extraction protocols for fecal microbiome samples were evaluated for their
effects on protein yields, peptide identifications, protein group
identifications, taxonomic compositions and functional category distributions.
While different protocols favor different microbial taxa and protein functions,
our results suggest that a protein extraction protocol using sodium dodecyl
sulfate (SDS) and ultrasonication provides the best performance for general
shotgun metaproteomics studies.
PMID- 28705726
TI - Dual organ beneficial effects of metformin in cirrhotic rats with hepatopulmonary
syndrome.
PMID- 28705727
TI - The Piezo1 protein ion channel functions in human nucleus pulposus cell apoptosis
by regulating mitochondrial dysfunction and the endoplasmic reticulum stress
signal pathway.
AB - The Piezo1 protein ion channel is a novel mechanical stretch-activated ion
channel (SAC) closely related to mechanical signals. Mechanotransduction plays a
crucial role in organ development and homeostasis. Previous studies identified
Piezo1 and demonstrated that it is distinct from other ion channels with well
established roles in lower organisms. Mechanical stretch-activated ion channels
from other organisms are not conserved in mammals or do not act as mechanically
activated channels in mammals. In the current study, we explored the role of the
Piezo1 ion channel in human nucleus pulposus cell (NP cell) apoptosis through
mechanical force-induced mitochondrial dysfunction and endoplasmic reticulum
stress. Reverse Transcription Polymerase chain reaction (RT-PCR),
immunofluorescence, immunohistochemistry and Annexin V binding and propidium
iodide analyses revealed that the Piezo1 protein ion channel was highly expressed
in human NP cells, which are the primary cells that comprise the intervertebral
disc. In patients with intervertebral disc degeneration (IVDD), the Piezo1
protein may play a crucial role in human NP cell apoptosis through mitochondrial
dysfunction and endoplasmic reticulum stress under abnormal loading conditions.
This study also verified that human NP cells have an intimate connection with the
cytoskeleton upon treatment of the cells with the Piezo1 blocking peptide GsMTx4
from tarantula venom. In summary, Piezo1 functions in human NP cell apoptosis,
which may be one underlying mechanism of apoptosis induced by abnormal loading in
IVDD patients.
PMID- 28705728
TI - Single mandibular implant study (SMIS) - masticatory performance - results from a
randomized clinical trial using two different loading protocols.
AB - OBJECTIVES: This multi-centre randomized controlled trial was conducted to
investigate, whether the masticatory performance of elderly edentulous patients
is improved by placement of a single implant in the midline of the edentulous
mandible, and whether improvements differ with respect to the loading protocol,
i.e., implant is loaded either directly or three months later after second stage
surgery. METHODS: Edentulous seniors aged 60-89 years were screened according to
inclusion and exclusion criteria and 163 underwent implant placement. Of those,
158 were randomly assigned either to the direct loading group A (n=81) or the
conventional loading group B (n=77). Chewing efficacy was obtained before
treatment, one month after implant placement during the submerged healing phase
(only group B) and 1 and 4 months after implant loading. RESULTS: The masticatory
performance increased over time in both groups. Four months after loading, a
significant increase was observed for both groups compared to the baseline data
without implant (p<=0.05). However, between the two groups, chewing efficiency
did not differ significantly at any point in time (p>0.05). CONCLUSIONS: A single
midline implant in the edentulous mandible increases masticatory performance
significantly, independently from the loading protocol. CLINICAL SIGNIFICANCE: A
single midline implant in the edentulous mandible increases masticatory
performance. The loading protocol has no influence.
PMID- 28705729
TI - Nanomedicine and epigenome. Possible health risks.
AB - Nanomedicine is an emerging field that combines knowledge of nanotechnology and
material science with pharmaceutical and biomedical sciences, aiming to develop
nanodrugs with increased efficacy and safety. Compared to conventional
therapeutics, nanodrugs manifest higher stability and circulation time, reduced
toxicity and improved targeted delivery. Despite the obvious benefit, the
accumulation of imaging agents and nanocarriers in the body following their
therapeutic or diagnostic application generates concerns about their safety for
human health. Numerous toxicology studies have demonstrated that exposure to
nanomaterials (NMs) might pose serious risks to humans. Epigenetic modifications,
representing a non-genotoxic mechanism of toxicant-induced health effects, are
becoming recognized as playing a potential causative role in the aetiology of
many diseases including cancer. This review i) provides an overview of recent
advances in medical applications of NMs and ii) summarizes current evidence on
their possible epigenetic toxicity. To discern potential health risks of NMs,
since current data are mostly based upon in vitro and animal models, a better
understanding of functional relationships between NM exposure, epigenetic
deregulation and phenotype is required.
PMID- 28705730
TI - Emotions as discrete patterns of systemic activity.
AB - Emotions organize human and animal behaviour by automatically adjusting their
actions at multiple physiological and behavioural scales. Recently, pattern
recognition techniques have emerged as an important tool for quantifying the
neural, physiological, and phenomenological organization of emotions in humans.
Here we review recent advances in our understanding of the human emotion system
from the viewpoint of pattern recognition studies, focussing on neuroimaging
experiments. These studies suggest, in general, clear and consistent categorical
structure of emotions across multiple levels of analysis spanning expressive
behaviour, subjective experiences, physiological activity, and neural activation
patterns. In particular, the neurophysiological data support the view of multiple
discrete emotion systems that are organized in a distributed fashion across the
brain, with no clear one-to-one mapping between emotions and brain regions.
However, these techniques are inherently limited by the choice of a priori
emotion categories used in the studies, and cannot provide direct causal evidence
for brain activity-emotion relationships.
PMID- 28705731
TI - Do glucocorticoids mediate the link between environmental conditions and telomere
dynamics in wild vertebrates? A review.
AB - Following the discoveries of telomeres and of their implications in terms of
health and ageing, there has been a growing interest into the study of telomere
dynamics in wild vertebrates. Telomeres are repeated sequences of non-coding DNA
located at the terminal ends of chromosomes and they play a major role in
maintaining chromosome stability. Importantly, telomeres shorten over time and
shorter telomeres seem to be related with lower survival in vertebrates. Because
of this potential link with longevity, it is crucial to understand not only the
ecological determinants of telomere dynamics but also the regulatory endocrine
mechanisms that may mediate the effect of the environment on telomeres. In this
paper, we review the relationships that link environmental conditions,
glucocorticoids (GC, the main hormonal mediator of allostasis) and telomere
length in vertebrates. First, we review current knowledge about the determinants
of inter-individual variations in telomere length. We emphasize the potential
strong impact of environmental stressors and predictable life-history events on
telomere dynamics. Despite recent progress, we still lack crucial basic data to
fully understand the costs of several life-history stages and biotic and abiotic
factors on telomere length. Second, we review the link that exists between GCs,
oxidative stress and telomere dynamics in vertebrates. Although circulating GC
levels may be closely and functionally linked with telomere dynamics, data are
still scarce and somewhat contradictory. Further laboratory and field studies are
therefore needed not only to better assess the proximate link between GC levels
and telomere dynamics, but also to ultimately understand to what extent GCs and
telomere length could be informative to measure the fitness costs of specific
life-history stages and environmental conditions. Finally, we highlight the
importance of exploring the functional links that may exist between coping
styles, the GC stress response, and telomere dynamics in a life-history
framework. To conclude, we raise new hypotheses regarding the potential of the GC
stress response to drive the trade-off between immediate survival and telomere
protection.
PMID- 28705732
TI - Feasibility of whole body hypothermia for neonates without congenital heart
defects surviving in-hospital cardiac arrest unrelated to perinatal asphyxia.
PMID- 28705733
TI - Platelet oxidative stress as a novel target of cardiovascular risk in frail older
people.
AB - The average lifespan of humans and the percentage of people entering the 65 and
older age group are growing rapidly. Within this age group, cardiovascular
diseases (CVD) increase steeply and are the most common cause of death. During
aging, experimental and clinical studies support the pivotal role played by
reactive oxidant species in the mechanism of platelet activation. Frailty has
been implicated as a causative and prognostic factor in patients with CVD.
Oxidative stress is increased in frail older people, and may lead to accelerated
aging and higher incidence of oxidative diseases such as CVD. The present article
aims to highlight the relative contribution of platelet oxidative stress as a key
target of frailty in elderly people with CVD.
PMID- 28705734
TI - Ablation-related ulcer on a migrating esophagus in association with deep
inspiration.
PMID- 28705735
TI - Charge balanced direct current carousel-A gentler yet targeted approach to
modulate sympathetic signaling in the heart.
PMID- 28705736
TI - A worldwide experience of the management of battery failures and chronic device
retrieval of the Nanostim leadless pacemaker.
AB - BACKGROUND: The Nanostim leadless pacemaker (LP) met the primary endpoints in an
investigational device exemption trial, and was shown to be fully retrievable
percutaneously. In October 2016, St Jude Medical issued a worldwide alert of a
battery malfunction that caused lost pacing output and LP communication.
OBJECTIVE: To report the battery failure mechanism and incidence and the
worldwide patient management, including device retrieval experiences. METHODS:
The affected LP battery is a custom lithium-carbon monofluoride cell. These were
returned after failure and underwent analysis assessing electronics and battery
performance. Data were collected in ongoing clinical studies when LPs were
abandoned or retrieved. RESULTS: Of 1423 LPs implanted worldwide, there were 34
battery failures, occurring at 2.9 +/- 0.4 years with no instances of associated
patient injury. Analysis of returned batteries revealed an increase in battery
resistance caused by insufficient electrolyte availability at the cathode/anode
interface. A total of 66 of 73 retrieval attempts were successful (90.4%; implant
duration range: 0.2-4.0 years). The LP docking button was inaccessible in 6
patients, and the docking button detached from the LP during retrieval in 1
patient. There was 1 case of arteriovenous fistula and another case of the LP
docking button migrating into the pulmonary artery. There were also 115 non-LP
retrieval patients after the advisory who received an additional pacemaker, with
no adverse device-to-device interactions reported. CONCLUSION: As with standard
pacers, LPs can have critical battery failures. Chronic retrieval of LPs is safe
and efficacious.
PMID- 28705737
TI - Leptin regulation of inward membrane currents, electrical activity and LH release
in isolated bovine gonadotropes.
AB - Leptin, a peptide hormone produced by adipocytes, is recognized as one of the
signals involved in the onset of reproductive activity. The leptin receptor has
been found in hypothalamic neurons and pituitary gonadotropes, suggesting that
the hormone may act at both sites to stimulate the secretion of GnRH and
consequently, FSH and LH. In response to a stimulus such as a hypothalamic
secretagogue, gonadotropes respond with changes in electrical activity,
intracellular Ca2+ and hormone release. The main aim of this report was to
investigate whether leptin promotes a change in the electrical and secretory
activities of bovine gonadotropes. After 48 h of treatment with leptin (10 nM)
significant changes in the action potential properties were observed in
gonadotropes, which included an increase in amplitude, time-to-pike and post
hyperpolarization, as well as a decrease in firing threshold. Likewise, leptin
induced a significant (~1.3-fold) up-regulation of voltage-gated Na+ channel
current density, and a selective increase (~2.1-fold) in Ca2+ current density
through high voltage-activated channels. Consistent with this, leptin enhanced
GnRH-induced secretion of LH measured by ELISA. We suggest that leptin enhances
membrane expression of voltage-gated Na+ and Ca2+ channels, which results in a
modulation of the action potential properties and an increase in hormone release
from gonadotropes.
PMID- 28705738
TI - Identification of novel potential scaffold for class I HDACs inhibition: An in
silico protocol based on virtual screening, molecular dynamics, mathematical
analysis and machine learning.
AB - Histone deacetylases (HDACs) family has been widely reported as an important
class of enzyme targets for cancer therapy. Much effort has been made in
discovery of novel scaffolds for HDACs inhibition besides existing hydroxamic
acids, cyclic peptides, benzamides, and short-chain fatty acids. Herein we set up
an in-silico protocol which not only could detect potential Zn2+ chelation bonds
but also still adopted non-bonded model to be effective in discovery of Class I
HDACs inhibitors, with little human's subjective visual judgment involved. We
applied the protocol to screening of Chembridge database and selected out 7
scaffolds, 3 with probability of more than 99%. Biological assay results
demonstrated that two of them exhibited HDAC-inhibitory activity and are thus
considerable for structure modification to further improve their bio-activity.
PMID- 28705739
TI - Long noncoding RNA linc00346 promotes the malignant phenotypes of bladder cancer.
AB - BACKGROUND: More and more reports have demonstrated that long noncoding RNAs
(lncRNAs) play an important role in the development of a variety of carcinomas,
including bladder cancer. However, only a small fraction of them have been
characterized. Linc00346 have been found to be upregulated in bladder cancer
tissues compared to normal tissues in a microarray-based lncRNA profiling study.
In this study, we would like to explore the expression pattern and functional
role of linc00346 in bladder cancer. METHODS: We determined the expression of
linc00346 in a cohort of bladder cancer tissues with matched normal tissues as
well as human bladder cancer cell lines. We investigated the biological function
of linc00346 with CCK-8 assay, colony formation assay, flow cytometry analysis,
transwell assay and tumor xenografts mice model. RESULTS: We found that linc00346
was upregulated in bladder cancer tissues compared to normal tissues. Knockdown
of linc00346 inhibited bladder cancer cell proliferation and migration, induced
cell cycle arrest and cell apoptosis. CONCLUSION: Our study demonstrates that
linc00346 could be a potential oncogene and a therapeutic target in bladder
cancer.
PMID- 28705740
TI - Proteomics analysis of human placenta reveals glutathione metabolism dysfunction
as the underlying pathogenesis for preeclampsia.
AB - Hypertensive disorder in pregnancy (HDP) refers to a series of diseases that
cause the hypertension during pregnancy, including HDP, preeclampsia (PE) and
eclampsia. This study screens differentially expressed proteins of placenta
tissues in PE cases using 2D LC-MS/MS quantitative proteomics strategy. A total
of 2281 proteins are quantified, of these, 145 altering expression proteins are
successfully screened between PE and control cases (p<0.05). Bioinformatics
analysis suggests that these proteins are mainly involved in many biological
processes, such as oxidation reduction, mitochondrion organization, and acute
inflammatory response. Especially, the glutamine metabolic process related
molecules, GPX1, GPX3, SMS, GGCT, GSTK1, NFkappaB, GSTT2, SOD1 and GCLM, are
involved in the switching process from oxidized glutathione (GSSG) conversion to
the reduced glutathione (GSH) by glutathione, mercapturic acid and arginine
metabolism process. Results of this study revealed that glutathione metabolism
disorder of placenta tissues may contribute to the occurrence of PE disease.
PMID- 28705741
TI - Acuity, treatment times, and patient experience in Freestanding Emergency
Departments affiliated with academic institutions.
PMID- 28705742
TI - An acute oral intoxication with haloperidol decanoate.
AB - Haloperidol decanoate is a typical antipsychotic drug used as maintenance therapy
for schizophrenia and mood disorders formulated as an ester for intramuscular
injection. Cases of oral haloperidol decanoate intoxications have not been
described in literature. In this report, we present for the first time a case of
an oral ingestion of haloperidol decanoate of a young woman who presented to the
emergency department following an intentional oral ingestion of 1 ampoule of
haloperidol decanoate 100mg. At presentation, she had a bilateral rest tremor of
both hands and mild hypothermia. No other obvious signs of an intoxication were
observed. She was treated with a single dose of activated charcoal and laxative
and was admitted to the intensive care for rhythm monitoring and observation.
During the night the QTc interval increased to 453ms, but stayed within the
normal range. Haloperidol plasma levels increased as well, but also stayed within
therapeutic ranges. These findings indicate that treatment with oral activated
charcoal was sufficient to prevent any serious events.
PMID- 28705743
TI - The influence of crowding on clinical practice in the emergency department.
AB - BACKGROUND: This study aimed to clarify the association between the crowding and
clinical practice in the emergency department (ED). METHODS: This 1-year
retrospective cohort study conducted in two EDs in Taiwan included 70,222 adult
non-trauma visits during the day shift between July 1, 2011, and June 30, 2012.
The ED occupancy status, determined by the number of patients staying during
their time of visit, was used to measure crowding, grouped into four quartiles,
and analyzed in reference to the clinical practice. The clinical practices
included decision-making time, patient length of stay, patient disposition, and
use of laboratory examinations and computed tomography (CT). RESULT: The four
quartiles of occupancy statuses determined by the number of patients staying
during their time of visit were <24, 24-39, 39-62, and >62. Comparing >62 and <24
ED occupancy statuses, the physicians' decision-making time and patients' length
of stay increased by 0.3h and 1.1h, respectively. The percentage of patients
discharged from the ED decreased by 15.5% as the ED observation, general ward,
and intensive care unit admissions increased by 10.9%, 4%, and 0.7%,
respectively. CT and laboratory examination slightly increased in the fourth
quartile of ED occupancy. CONCLUSION: Overcrowding in the ED might increase
physicians' decision-making time and patients' length of stay, and more patients
could be admitted to observation units or an inpatient department. The use of CT
and laboratory examinations would also increase. All of these could lead more
patients to stay in the ED.
PMID- 28705744
TI - The relationship between ocular trauma and substance abuse in emergency
department patients.
AB - INTRODUCTION: Eye injury is the second most common cause of visual impairment and
a leading cause of monocular blindness in the United States. There are
approximately 6 million ED visits related to drug use annually, including misuse
or abuse of pharmaceuticals and illicit drug use. The purpose of this study was
to assess the relationship between ocular trauma and substance abuse among
emergency department patients and to assess that relationship with demographic
factors, including age and gender. METHODS: This study was a retrospective,
observational study conducted at Miami Valley Hospital, an urban hospital ED, in
Dayton, Ohio. Eligible participants included consecutive ocular trauma patients
identified by the Trauma Registry from January 2014 through January 2016. Data
were collected from the ED medical record including demographic information,
mechanism of injury, visual acuity, slit lamp exam findings, ED procedures,
inpatient procedures, toxicology results, ED diagnosis, ED disposition, and eye
exam. RESULTS: Among 229 patients, the mean age was 44 (range 14-93). 73% of
patients were male. Most patients were White (74%), followed by African American
(21%), Hispanic (2%), and other (3%). Most patients arrived by ambulance (62%),
followed by helicopter (30%), and walk-ins (18%). Most patients were admitted to
the hospital (79%). Mechanisms of injury included motor vehicle accidents (31%)
and cases of assault (28%). Most ocular trauma involved the external eye (44%),
the anterior chamber (28%), the orbit (25%) and the globe (22%). The incidence of
substance abuse in this patient population was high. Of the patients tested for
alcohol (N=143), 49% tested positive. Among 98 patients who received a urine
toxicologic screen, 63% tested positive for at least one illicit substance,
including opiates (39%), cocaine (12%), benzodiazepines (25%), and/or THC (27%).
There was no significant association between substance abuse and ED disposition.
CONCLUSION: Mechanisms of eye injury included primarily motor vehicle accidents
and assault. Most ocular trauma involved the external eye, the anterior chamber,
the orbit, and the globe. The incidence of alcohol and illicit substance abuse is
high among ED patients with ocular trauma.
PMID- 28705745
TI - Massive diltiazem and metoprolol overdose rescued with extracorporeal life
support.
AB - The management of overdoses of cardioactive medications in the emergency
department can be challenging. The reversal of severe toxicity from one or more
types of cardioactive medication may fail maximal medical therapies and require
extreme invasive measures such as transvenous cardiac pacing and extracorporeal
life support. We present a case of massive diltiazem and metoprolol overdose
refractory to maximal medical therapy, including intravenous calcium, glucagon,
vasopressors, high dose insulin, and lipid emulsion. The patient experienced
refractory bradydysrhythmia that responded only to transvenous pacing.
Extracorporeal life support was initiated and resulted in successful organ
perfusion and complete recovery of the patient. This case highlights the
potential utility of extracorporeal life support in cases of severe toxicity due
to multiple cardioactive medications.
PMID- 28705746
TI - First report of Ehrlichia infection in goats, China.
AB - Ehrlichiosis is an emerging infectious disease of domestic animals which is
transmitted by ticks. This disease has been reported earlier in most parts of
China in dogs, cattle and humans, but there is no published data regarding this
disease in goats. The present study provided the evidence of Ehrlichia infection
in goats in Wuhan, China on the basis of clinical signs, gross lesions, serum
biochemical, histopathological and PCR. Twenty four goats were presented to the
veterinary hospital of Huazhong Agricultural University during July, 2016. The
goats were diagnosed for Ehrlichia in monocytic and granulocytic forms by blood
smear examination. Further confirmation was done by PCR examination, while
histopathological examination revealed degeneration and inflammation in different
tissues. The biochemical criterion and blood samples analysis showed significant
(P < 0.05) changes. The present study reported that goats are naturally exposed
to Ehrlichia infection. To the best of our knowledge, this is the first clinical
report of Ehrlichia infection in goats infested with infected ticks.
PMID- 28705747
TI - Synthesis of phytochemicals-stabilized gold nanoparticles and their biological
activities against bacteria and Leishmania.
AB - Nanoscale materials have shown promising results in the field of medicine as
therapeutic agents and drugs delivery vehicles. In the current study, gold
nanoparticles (AuNPs) were prepared by a green and facile method using the
aqueous extract of Rhazya stricta decne as a source of reducing and stabilizing
agents. The bio-fabricated AuNPs were characterized by UV-visible spectroscopy, X
ray diffraction (XRD), Transmission electron microscopy (TEM) and FTIR
spectroscopy. Antimicrobial activities of the biosynthesized AuNPs were tested
against Leishmania tropica (HTD7), E. coli and S. aureus. AuNPs were the most
effective agents in inhibiting the growth of intra-THP-1 amastigotes at 100
MUg/mL concentration (IC50 = 43 MUg/mL) after 48-h incubation. In addition, the
prepared AuNPs also displayed good activity against E. coli (MIC = 25.0 MUg/mL)
and Bacillus subtilis (50.0 MUg/mL). Interestingly, biogenic AuNPs did not
exhibit cytotoxic effect against the THP-1 cells after 24 h exposure. The
findings of this study conclude that phytochemicals-stabilized AuNPs could be a
safe and effective source of antimicrobial agents.
PMID- 28705748
TI - Effect of secondary metabolite of Actinidia deliciosa on the biofilm and extra
cellular matrix components of Acinetobacter baumannii.
AB - Acinetobacter baumannii, opportunistic nosocomial pathogen, increases gradually
in the clinical setup. The high level of resistance mechanisms acquired by these
bacteria makes their eradication difficult and biofilm formation is one of them.
Biofilm comprises of closely packed bacterial population crowded together by
extra-cellular matrix (ECM). ECM contains bacterial secreted polymers such as
exopolysaccharides (EPS), proteins and extracellular-DNA (e-DNA) and rarely
amyloidogenic proteins. Biofilm offers protection of underlying bacterial
population against chemotherapeutic agents and host immune system. Therefore,
present efforts are focused to find a novel therapeutic that targets biofilm
associated infections. Plants are used as a natural therapeutic for numerous
ailments. In order to find an alternative of the available antibacterial drugs,
we have focused on the natural herbal active compounds. In this study, we have
extracted active compounds from various medicinal plants and screened its anti
biofilm activity against carbapenem resistant strain of A. baumannii. Results
showed that polar extract of kiwi (Actinidia deliciosa) and clove (Syzygium
aromaticum) exhibit effective anti-biofilm activity. These two plants were also
used for their phytochemical screening and TLC profiling to find out the
constituting secondary metabolites. Actinidia deliciosa extract contains an
alkaloid (sanquinarine) as well as a flavonoid (hydroxyflavone). Anti-biofilm
effect of this extract on the ECM of A. baumannii showed that it reduces EPS,
protein and eDNA contents in the ECM. Proteins of ECM have also shown to form
amyloid like structure, which was evident from its interaction with the Congo
Red. CFU counting after Actinidia deliciosa extract treatment also supported the
results. Therefore, it can be concluded that polar extract of A. deliciosa can be
used to find suitable alternative therapeutic to control biofilm formation by
carbapenem resistant strain of Acinetobacter baumannii.
PMID- 28705749
TI - In vitro effect of metrifonate on the indices of oxidative stress in
Gigantocotyle explanatum.
AB - Helminth infections in general and digenetic trematodes in particular cause a
huge economic loss globally to our livestock. Gigantocotyle explanatum is a
digenetic amphistome that infects the bile ducts of water buffalo and are highly
prevalent in tropical and sub-tropical countries. In the present study, effects
of an organophosphate compound, Metrifonate (MF) in three doses, viz., 9.4 * 10-5
M (Dose I), 14.4 * 10-5 M (Dose II), and 19.4 * 10-5 M (Dose III), have been
studied in vitro, on the motility and on some enzymatic and non-enzymatic
oxidative stress indices in G. explanatum. The worm's motility and their non
enzymatic oxidative stress biomarkers like lipid peroxides measured as
thiobarbituric acid-reactive substances (TBARS) and reduced glutathione (GSH)
were disrupted significantly in a dose-dependent manner. However, the enzymatic
oxidative stress biomarkers like glutathione-S-transferase (GST) and superoxide
dismutase (SOD) were affected by MF treatment in a biphasic manner. Exposure to
Dose I significantly stimulated the activities of both GST and SOD, whereas
exposure to Doses II and III resulted into significant inhibition in a dose
dependent manner. Our findings suggest that MF has potential to be a strong and
effective anthelmintic, however, further studies in vitro as well as in vivo are
needed to explore further these observations and understand the exact mode of MF
action in G. explanatum and other trematodes of veterinary economic importance.
PMID- 28705750
TI - Heart rate variability reactivity and new romance: Cause or consequence?
AB - There are documented physiological differences between single and coupled
individuals during the "honeymoon period" of nascent romantic relationships. One
such difference is in autonomic reactivity, specifically heart rate variability
(HRV) reactivity. This finding had previously been interpreted as evidence of a
stress buffering effect of relationship formation. The present study explored
among university women two competing longitudinal hypotheses conceptualizing
differences in HRV reactivity as either a cause or a consequence of romantic
relationship formation. Results did not support the hypothesis that HRV
reactivity changes as a consequence of beginning a new romantic relationship.
Instead, lower HRV reactivity predicted greater relationship formation amongst
women with low BMI and higher resting HRV. The functioning of the heart therefore
predicted the likelihood that an individual would find love. These interactions
may be the result of differing success rates of various mating strategies for
women with low and high BMI and HRV.
PMID- 28705751
TI - Single-Port Laparoscopy vs Conventional Laparoscopy in Benign Adnexal Diseases: A
Systematic Review and Meta-Analysis.
AB - Single-port laparoscopy (SPL) was developed approximately 30 years ago in
minimally invasive surgery. Literature comparing SPL with conventional
laparoscopy (CL) for adnexal surgery (i.e., cystectomy and adnexectomy) is
inconsistent. The objective of this systematic review and meta-analysis was to
evaluate the advantage of SPL over CL for adnexal surgery. PubMed, Embase, and
MEDLINE were searched for publications in English and in French published between
1975 and November 2015 using the following key words: (((single port) or (single
site) or (one port) or (single-port access laparoscopy) or (single-site
laparoscopy) or (laparoscopic single-site surgery)) and ((adnexal disease) or
(ovarian cystectomy) or (ovariectomy) or (adnexectomy))) not (pregnancy). The
primary outcome was postoperative pain assessed at 24 hours postsurgery. The
secondary outcomes were postoperative pain at 6 and 48 hours postsurgery,
analgesic consumption, operative time, blood loss, laparotomy conversion rate,
mean hospital stay, and cosmetic results at 1 month. Sixteen relevant articles
were identified by electronic search. The pooled analysis of randomized trials
showed no significant difference between SPL and CL in terms of postoperative
pain at 6 and 24 hours, blood loss, mean length of hospital stay, cosmetic
results, and laparotomy conversion rate; however, operative time was longer for
SPL (p = .03). The pooled analysis including all the selected studies showed no
significant difference for all of these outcomes. This review and meta-analysis
found no significant difference between SPL and CL for adnexal surgery, except
for operative time. Further large-scale randomized trials should be conducted to
investigate the potential advantages of SPL over CL before this laparoscopic
approach can be recommended.
PMID- 28705752
TI - Polymorphisms of the human platelet antigen-1, -2, -3, -5, and -15 systems and
acute cellular liver transplant rejection.
AB - The human platelet antigen (HPA)-1, -2, -3, -5, and -15 systems are characterized
as polymorphic alloantigens expressed on platelets and endothelial cells. In this
retrospective study, we investigated, whether HPA-1, -2, -3, -5, and -15
incompatibilities are associated with acute cellular liver transplant rejection.
A total of 96 Caucasian liver transplant recipients and corresponding donors were
analyzed, 43 with biopsy proven acute cellular rejection (BPAR) and 53 without
acute cellular rejection (No-BPAR). Polymorphisms of mentioned HPA systems were
determined by polymerase chain reaction-sequence specific primers (PCR-SSP). Our
data demonstrate that acute cellular rejection episodes were associated with HPA
3 incompatibility (58% HPA-3 incompatibility in BPAR group vs. 32% HPA-3
incompatibility in No-BPAR group, p=0.013). Furthermore, the frequency of HPA-3bb
genotype was significantly higher in BPAR recipients as compared to No-BPAR
recipients (30% vs 6%, p=0.002). On the other hand, there was no association
between acute cellular rejection and the other tested HPA systems. We conclude
that in the Caucasian population the HPA-3 system confers susceptibility to acute
cellular rejection after liver transplantation.
PMID- 28705753
TI - Invasive Fungal Infections Secondary to Traumatic Injury.
AB - Invasive fungal infection (IFI) is a rare but serious complication of traumatic
injury. The purpose of this article is to review the epidemiology, natural
history, mycology, risk factors, diagnosis, treatment, and outcomes associated
with post-traumatic IFI in military and civilian populations. The epidemiology of
post-traumatic IFI is poorly characterized, but incidence appears to be rising.
Patients often suffer from severe injuries and require extensive medical
interventions. Fungi belonging to the order Mucorales are responsible for most
post-traumatic IFI in both civilian and military populations. Risk factors differ
between these cohorts but include specific injury patterns and comorbidities.
Diagnosis of post-traumatic IFI typically follows positive laboratory results in
the appropriate clinical context. The gold standard of treatment is surgical
debridement in addition to systemic antifungal therapy. Patients with post
traumatic IFI may be at greater risk of amputation, delays in wound healing,
hospital complications, and death as compared to trauma patients who do not
develop IFI. More research is needed to understand the factors surrounding the
development and management of post-traumatic IFI to reduce the significant
morbidity and mortality associated with this disease.
PMID- 28705754
TI - Progression of Lyme disease to Bell's Palsy despite treatment with doxycycline.
PMID- 28705755
TI - Isolation and Whole-genome Sequence Analysis of the Imipenem Heteroresistant
Acinetobacter baumannii Clinical Isolate HRAB-85.
AB - OBJECTIVES: Heteroresistance is a phenomenon in which there are various responses
to antibiotics from bacterial cells within the same population. Here, we isolated
and characterised an imipenem heteroresistant Acinetobacter baumannii strain
(HRAB-85). METHODS: The genome of strain HRAB-85 was completely sequenced and
analysed to understand its antibiotic resistance mechanisms. Population analysis
and multilocus sequence typing were performed. RESULTS: Subpopulations grew in
the presence of imipenem at concentrations of up to 64MUg/mL, and the strain was
found to belong to ST208. The total length of strain HRAB-85 was 4,098,585bp with
a GC content of 39.98%. The genome harboured at least four insertion sequences:
the common ISAba1, ISAba22, ISAba24, and newly reported ISAba26. Additionally, 19
antibiotic-resistance genes against eight classes of antimicrobial agents were
found, and 11 genomic islands (GIs) were identified. Among them, GI3, GI10, and
GI11 contained many ISs and antibiotic-resistance determinants. CONCLUSIONS: The
existence of imipenem heteroresistant phenotypes in A. baumannii was
substantiated in this hospital, and imipenem pressure, which could induce
imipenem-heteroresistant subpopulations, may select for highly resistant strains.
The complete genome sequencing and bioinformatics analysis of HRAB-85 could
improve our understanding of the epidemiology and resistance mechanisms of
carbapenem-heteroresistant A. baumannii.
PMID- 28705756
TI - Emergence of colistin-resistant Escherichia coli clinical isolates harboring mcr
1 in Vietnam.
AB - The mcr-1 was first detected on a plasmid in colistin-resistant Escherichia coli
from livestock and patients in China. We described here the emergence of colistin
resistant E. coli clinical isolates harboring mcr-1 on the chromosomes in
Vietnam. To our knowledge, this is the first report of hospital-acquired E. coli
isolates harboring mcr-1 in a medical setting in Vietnam.
PMID- 28705757
TI - Social Support in Newly Diagnosed People living With HIV: Expectations and
Satisfaction Along Time, Predictors, and Mental Health Correlates.
AB - Social support usually decreases following HIV diagnosis, and decreased support
is related to worsening mental health. We investigated the evolution of social
support after HIV diagnosis and its relationship to anxiety, depression, and
resilience, and sought to develop a social support prediction model. There were
119 newly diagnosed Spanish speakers who participated in this longitudinal study,
completing measures of social support, internalized stigma, disclosure concerns,
degree of disclosure, coping, anxiety, depression, and resilience. Bivariate
associations and multiple regression analyses were performed. Results showed that
the highest levels of support arose from friends, health care providers, and
partners, and that social support decreased following diagnosis. Subsequent
social support was negatively predicted by avoidance coping and positively by
approach coping, steady partnership, and disclosure. It was significantly
associated with decreased anxiety and depression and higher resilience.
Interventions should seek to promote mental health in people living with HIV by
increasing social support.
PMID- 28705758
TI - What the Rest of the World Should Know About HIV: Perceptions From Adults Living
With HIV in the Dominican Republic.
PMID- 28705759
TI - Implementation of an electronic checklist in the ICU: Association with improved
outcomes.
AB - OBJECTIVE: To assess the impact of an electronic checklist during the morning
rounds on ventilator-associated pneumonia (VAP) in the intensive care unit (ICU).
PATIENTS AND METHODS: We conducted a retrospective, before/after study in a
single ICU of a university hospital. A systematic electronic checklist focusing
on guidelines adherence was introduced in January 2012. From January 2008 to June
2014, we screened patients with ICU stay durations of at least 48hours.
Propensity score-matched analysis with conditional logistic regression was used
to compare the rate of VAP and number of days free of invasive devices before and
after implementation of the electronic checklist. RESULTS: We analysed 1711
patients (before group, n=761; after group, n=950). The rates of VAP were 21% and
11% in the before and after groups, respectively (p<0.001). In propensity-score
matched analysis (n=742 in each group), VAP occurred in 151 patients (21%) during
the before period compared with 72 patients (10%) during the after period (odds
ratio [OR]=0.38; 95% confidence interval [CI]=0.27-0.53). The after group showed
increases in ICU-free days (OR=1.05; 95% CI=1.04-1.07) and mechanical ventilation
free days (OR=1.03; 95% CI=1.01-1.04). CONCLUSION: In this matched before/after
study, implementation of an electronic checklist was associated with positive
effects on patient outcomes, especially on VAP. Further prospective studies are
needed to confirm these observations.
PMID- 28705760
TI - Synthetic analogues of cyanobacterial alkaloid cylindrospermopsin and their
toxicological activity.
AB - Cylindrospermopsin (CYN) is a naturally occurring alkaloid produced by a variety
of cyanobacteria and known to induce oxidative stress-mediated toxicity in
eukaryotic cells. Despite extensive research on the mechanism of CYN toxicity, an
understanding of the structural features responsible for this toxicity and the
mechanism by which it can enter the cell are still not clear. It was established
that the presence of both the uracil and guanidine groups is essential in
biological activity of CYN whilst not much is known in this regard on the role of
tether that separates them and the attached hydroxyl group. Therefore, in the
present study we have prepared three synthetic analogues possessing uracil and
guanidine groups separated by a variable length tether (4-6 carbons) and
containing a hydroxyl function in a position orientation to CYN, together with a
tetracyclic analogue of CYN lacking the hydroxyl group at C-7. The toxicity of
these compounds was then compared with CYN and guanidinoacetate (GAA; the primary
substrate in CYN biosynthesis) in an in vitro model using human neutrophils
isolated from healthy subjects. The lowest activity measured by means of reactive
oxygen species generation, lipid peroxidation and cell death was observed for GAA
and the tetracyclic analogue. The greatest toxicity was found in an analogue with
a 6-carbon tether, but all three analogues and CYN caused rapid onset of redox
imbalance. These results add to the general understanding of CYN toxicity and
preliminary findings suggest that the -OH group at C-7 may be significant for the
cellular transport of CYN and/or be involved in its toxic activity inside the
cell, a hypothesis which requires further testing.
PMID- 28705761
TI - Factors of concern in a human 3D cellular airway model exposed to aerosols of
nanoparticles.
AB - Mucilair 3D bronchial airway models, cultured at an air-liquid interface, were
exposed to aerosols of copper oxide (CuO) nanoparticles in Vitrocell air exposure
modules. Four cell donors, four exposure modules and four exposure concentrations
were varied within four different exposure sessions using a statistical
experimental design called a hyper-Graeco-Latin square. Analysis of variance
techniques were used to investigate the effects of these factors on release and
RNA expression of inflammation markers monocyte chemoattractant protein-1 (MCP-1)
interleukines 6 and 8 (IL-6 and IL-8) an cytotoxicity marker lactate
dehydrogenase (LDH) determined 24h after exposure. The same techniques were also
used to conduct a global analysis on RNA expressions of 10,000 genes. There were
no major signs of cytotoxicity. Release of IL-6 and MCP-1 was affected by CuO
concentration, and, for MCP-1, by donor variation. IL-8 release was not affected
by these factors. However, gene expression of all three inflammation markers was
strongly affected by CuO concentration but not by the other factors. Further,
among the 10,000 genes involved in the global analysis of RNA expression, 1736
were affected by CuO concentration, 704 by donor variation and 269 by variation
among exposure sessions. The statistical design permitted the assessment of the
effect of CuO nanoparticles on 3D airway models independently of technical or
experimental sources of variation. We recommend using such a design to address
all potential sources of variation. This is especially recommended if test
materials are expected to be less toxic than CuO, because the variation among the
concentration levels could then be close to the variation among donors or
exposure sessions.
PMID- 28705762
TI - Flexible Connectors between Capsomer Subunits that Regulate Capsid Assembly.
AB - Viruses build icosahedral capsids of specific size and shape by regulating the
spatial arrangement of the hexameric and pentameric protein capsomers in the
growing shell during assembly. In the T=7 capsids of Escherichia coli
bacteriophage HK97 and other phages, 60 capsomers are hexons, while the rest are
pentons that are correctly positioned during assembly. Assembly of the HK97
capsid to the correct size and shape has been shown to depend on specific ionic
contacts between capsomers. We now describe additional ionic interactions within
capsomers that also regulate assembly. Each is between the long hairpin, the "E
loop," that extends from one subunit to the adjacent subunit within the same
capsomer. Glutamate E153 on the E-loop and arginine R210 on the adjacent
subunit's backbone alpha-helix form salt bridges in hexamers and pentamers.
Mutations that disrupt these salt bridges were lethal for virus production,
because the mutant proteins assembled into tubes or sheets instead of capsids. X
ray structures show that the E153-R210 links are flexible and maintained during
maturation despite radical changes in capsomer shape. The E153-R210 links appear
to form early in assembly to enable capsomers to make programmed changes in their
shape during assembly. The links also prevent flattening of capsomers and
premature maturation. Mutant phenotypes and modeling support an assembly model in
which flexible E153-R210 links mediate capsomer shape changes that control where
pentons are placed to create normal-sized capsids. The E-loop may be conserved in
other systems in order to play similar roles in regulating assembly.
PMID- 28705763
TI - Structure and Function of Peptide-Binding G Protein-Coupled Receptors.
AB - G protein-coupled receptors (GPCRs) are the largest family of cell surface
receptors and are important human drug targets. Of the 826 human GPCRs, 118 of
them recognize endogenous peptide or protein ligands, and 30 of the 118 are
targeted by approved drug molecules, including the very high-profile class B
glucagon-like peptide 1 receptor. In this review, we analyze the 21
experimentally determined three-dimensional structures of the known peptide
binding GPCRs in relation to the endogenous peptides and drug molecules that
modulate their cell signaling processes. Our integrated analyses reveal that half
of the marketed drugs and most of the drugs in clinical trials that interact with
peptide GPCRs are small molecules with a wide range of binding modes distinct
from those of large peptide ligands. As we continue to collect additional data on
these receptors from orthogonal approaches, including nuclear magnetic resonance
and electron microscopy, we are beginning to understand how these receptors
interact with their ligands at the molecular level and how improving the
pharmacology of GPCR signal transduction requires us to study these receptors
using multiple biophysical techniques.
PMID- 28705764
TI - A Survey of DDX21 Activity During Rev/RRE Complex Formation.
AB - HIV-1 requires a specialized nuclear export pathway to transport unspliced and
partially spliced viral transcripts to the cytoplasm. Central to this pathway is
the viral protein Rev, which binds to the Rev response element in stem IIB
located on unspliced viral transcripts and subsequently oligomerizes in a
cooperative manner. Previous work identified a number of cellular DEAD-box
helicases as in vivo binding partners of Rev, and siRNA experiments indicated a
functional role for many in the HIV replication cycle. Two DEAD-box proteins,
DDX1 and DDX3, had previously been shown to play a role in HIV pathogenesis. In
this study, another protein identified in that screen, DDX21, is tested for
protein and RNA binding and subsequent enzymatic activities in the context of the
Rev/RRE pathway. We found that DDX21 can bind to the RRE with high affinity, and
this binding stimulates ATPase activity with an enzymatic efficiency similar to
DDX1. Furthermore, DDX21 is both an ATP-dependent and ATP-independent helicase,
and both ATPase and ATP-dependent helicase activities are inhibited by Rev in a
dose-dependent manner, although ATP-independent helicase activity is not. A
conserved binding interaction between DDX protein's DEAD domain and Rev was
identified, with Rev's nuclear diffusion inhibitory signal motif playing a
significant role in binding. Finally, DDX21 was shown to enhance Rev binding to
the RRE in a manner similar to that previously described for DDX1, although DDX3
does not. These data indicate that DDX1 and DDX21 have similar biochemical
activities with regard to the Rev/RRE system, while DDX3 differs.
PMID- 28705765
TI - Terminal 14q32.33 deletion as a novel cause of agammaglobulinemia.
AB - Over the past decades, a pleiotropic spectrum of B-cell intrinsic defects leading
to early onset agammaglobulinemia and absent B cells has been described. Herein
we report terminal 14q32.33 deletion as a novel cause of agammaglobulinemia. We
describe a 20-year old man with a 1MB terminal 14q32.33 deletion resulting in a
loss of the entire Immunoglobulin heavy chain gene region of chromosome 14. The
patient presented with absent serum immunoglobulin levels and absent circulating
B cells since age 2. The clinical picture was dominated by severe episodes of
recurrent upper respiratory tract infections. In the literature, the most
prevalent features of terminal 14q32.33 deletions include mental disability,
facial malformation, hypotonia, seizures, and visual problems with retinal
abnormalities. Neither increased susceptibility to infections nor
agammaglobulinemia have been described as a manifestation of terminal 14q32.33
deletion. Thus, our findings expand the known clinical spectrum of terminal
14q32.33 deletion to include susceptibility to infections.
PMID- 28705766
TI - Patients with major depressive disorder exhibit reduced reward size coding in the
striatum.
AB - BACKGROUND: Anhedonia is a core symptom of major depressive disorder (MDD). While
recent evidence suggests that reduced motivation for reward may be a core feature
of anhedonia, the abnormalities in modulatory neural responses to variable reward
amounts in MDD patients remain unclear. We investigated whether MDD patients'
ability to represent variable-sized monetary rewards in the striatum is
disrupted. METHODS: Twelve MDD patients and 12 healthy volunteers completed an
assessment of psychometric status and participated in a functional magnetic
resonance imaging (fMRI) task that involved the anticipation of financial reward
(monetary incentive delay task). The size of the monetary reward was varied among
trial conditions and was cued with geometric stimuli. Patients participated in
additional fMRI sessions after a 6-week pharmacological treatment with
escitalopram, an SSRI. RESULTS: In healthy volunteers, striatal activity
increased in proportion to the size of the monetary reward during reward
anticipation. This pattern was altered in MDD patients, and significant group-by
reward size interaction effects were observed in the bilateral putamen and the
left ventral striatum. Reward sensitivity in motor response and striatum activity
at three regions were correlated in healthy controls. In MDD patients, this
neurobehavioral coupling was not observed. In addition, changes in the neural
reward sensitivity parameter at the left ventral striatum in response to
treatment were positively correlated with a reduction of depressive symptoms.
CONCLUSIONS: Patients with MDD exhibit reduced ability to modulate neural
response when adjusting for variable amount of reward. This result suggests that
reward size coding in the striatum may represent a neural correlate of
motivational anhedonia in MDD patients.
PMID- 28705767
TI - Common and distinct dysfunctional patterns contribute to triple network model in
schizophrenia and depression: A preliminary study.
AB - BACKGROUND: Schizophrenia (SCH) and depression (DEP) are prevalent psychiatric
disorders and share common and distinguished elements in their pathophysiology. A
triple network model composed of the default mode network (DMN), salience network
(SN) and central executive network (CEN) may represent a major abnormality across
several psychiatric disorders including SCH and DEP. However, common and distinct
dysfunctional patterns between SCH and DEP across three core networks remain
unclear. METHOD: Resting-state functional magnetic resonance imaging (fMRI) was
obtained in 20 patients with SCH, 20 patients with DEP and 20 healthy controls
(HC). Both functional connectivity (FC) and Granger causal connectivity across
DMN, SN and CEN were evaluated to uncover common and distinct dysfunctional
patterns between SCH and DEP. RESULTS: Two patient groups showed identical
abnormal causal connectivity between key nodes of DMN and SN, as well as opposing
aberrant FC of DMN-CEN and SN-CEN. Compared with HC, the FC between CEN and DMN
was increased in SCH while decreased in DEP. Conversely, DEP showed enhanced FC
between CEN and SN, whereas SCH showed decreased FC. LIMITATIONS: The sample size
was relatively small, and all participants were taking medication. CONCLUSIONS:
Our results identified common patterns including dysconnectivity between DMN and
SN, which may contribute to shared cognitive and affective impairment in DEP and
SCH. Moreover, opposing dysconnectivity patterns of DMN-CEN may be associated
with different self-referential processing abnormalities. These opposing
dysconnectivity patterns may indicate an unbalanced recruitment between SN and
CEN. Therefore, this study provides dysconnectivity patterns to advance the
understanding of the triple network model with regard to psychiatric disorders.
PMID- 28705768
TI - The clinical and microbiological characteristics of infections in burn patients
from the Formosa Fun Coast Dust Explosion.
AB - BACKGROUND/PURPOSE: Bloodstream infection is a leading cause of mortality among
burn patients. This study aimed to evaluate the risk factors, causative
pathogens, and the relationship between bloodstream infections and other
infections among burn patients from the Formosa Fun Coast Dust Explosion.
METHODS: This retrospective study evaluated the demographic and clinical
characteristics, infection types, causative pathogen(s), and isolates' antibiotic
susceptibilities from patients who were hospitalized between June 27 and
September 31, 2015. RESULTS: Fifty-eight patients were admitted during the study
period (36 males, mean age: 22.6 years). The mean burned total body surface area
(TBSA) was 40% for all patients. Eighteen (31%) patients with mean TBSA of 80%
had 66 episodes of bloodstream infections caused by 92 isolates. Twelve (18.2%)
episodes of bloodstream infections were polymicrobial. Acinetobacter baumannii
(19, 20.7%), Ralstonia pickettii (17, 18.5%), and Chryseobacterium
meningosepticum (13, 14.1%) were the most common pathogens causing bloodstream
infections. A high concordance rate of wound cultures with blood cultures was
seen in Staphylococcus aureus (3, 75%) and C. meningosepticum (8, 61.5%)
infections. However, no Ralstonia isolate was found in burn wounds of patients
with Ralstonia bacteremia. A high concordance rate of central venous catheter
cultures with blood cultures was noted in Ralstonia mannitolilytica (5, 62.5%)
and Chryseobacterium indologenes (3, 60%) infections. Approximately 21.1% of A.
baumannii strains were resistant to carbapenem. All S. aureus isolates were
susceptible to methicillin. CONCLUSIONS: Waterborne bacteria should be considered
in patients of burns with possible water contact. Empirical broad-spectrum
antibiotics should be considered for patients who were hospitalized for severe
sepsis, or septic shock with a large burn. Antibiotic treatment should be
administered based on the specific pathogens and their detection points.
PMID- 28705769
TI - The plasmid-mediated fosfomycin resistance determinants and synergy of fosfomycin
and meropenem in carbapenem-resistant Klebsiella pneumoniae isolates in Taiwan.
AB - BACKGROUND: Epidemiology of fosfomycin susceptibility and the plasmid-mediated
fosfomycinase genes of carbapenem-resistant Klebsiella pneumoniae (CRKP) isolates
in Taiwan remain unclear. METHODS: 642 CRKP clinical isolates were collected from
a nation-wide surveillance study (16 hospitals) in Taiwan in 2012-2013.
Antimicrobial susceptibilities were determined. PFGE and MLST determined the
clonal relatedness. Carbapenemases and fosfomycinases genes were detected by PCR,
and their flanking regions were determined by PCR and sequencing. Synergistic
activity of meropenem with fosfomycin was examined by the checkerboard method.
RESULTS: In total, 36.4% (234/642) of CRKP isolates in Taiwan were resistant to
fosfomycin. Among 234 fosfomycin-resistant CRKP isolates, PFGE analysis revealed
81 pulsotypes. Pulsotype XXIII (n = 63) was predominant and belonged to ST11. 71
had carbapnemases (65 blaKPC-2-positive, 1 blaVIM-1-positive and 5 blaIMP-8
positive) and 62 had fosfomycinases (35 fosA3-positive and 27 foskp96-positive).
Only 18.5% (5/27) of foskp96-positive isolates carried foskp96 and blaKPC-2,
while 71.4% (25/35) of fosA3-positive isolates contained fosA3 and blaKPC-2.
There were five types of flanking sequences for fosA3, and 85.7% (30/35) of fosA3
genes were flanked by IS26, suggesting possible horizontal gene transfer.
Synergistic effect of fosfomycin and meropenem was observed in all 25 randomly
selected pulsotype XXIII strains (100%; 25/25), even those containing
fosfomycinase (48%, 12/25) or carbapnemase (96%, 24/25). CONCLUSIONS: A clone
(pulsotype XXIII, ST11) has been found to be prevailing among fosfomycin
resistant CRKP in Taiwan. According to the in vitro data, the combination of
fosfomycin and meropenem is a potentially alternative choice.
PMID- 28705770
TI - In vitro activity of aminoglycosides, clofazimine, d-cycloserine and dapsone
against 83 Mycobacterium avium complex clinical isolates.
AB - BACKGROUND/PURPOSE: Treatment success rates for Mycobacterium avium complex (MAC)
diseases range from 50% to 55% only. To explore effective antimicrobials against
either Mycobacterium intracellulare or M. avium, we determined in vitro
activities of five aminoglycosides, clofazimine, dapsone and d-cycloserine
compared with primary (clarithromycin) and secondary (moxifloxacin and linezolid)
antimycobacterial agents. METHODS: 83 non-duplicate clinical MAC isolates were
collected from sputum and identified at the species level by PCR and restriction
enzyme analysis of the 65 kDa hsp and rpoB genes. Drug susceptibility testing was
performed using broth microdilution method. The fractional inhibitory
concentration was calculated to determine synergy between isepamicin and
clofazimine. RESULTS: High susceptibility rates of five aminoglycosides
(isepamicin, amikacin, kanamycin, streptomycin, capreomycin, 82.7-88%), d
cycloserine (82.7%), clofazimine (97.3%) and clarithromycin (92%) against M.
intracellulare, and 2 aminoglycosides (isepamicin, streptomycin, 87.5%), d
cycloserine (100%) and clarithromycin (100%) against M. avium were found. Dapsone
had no inhibitory activity and moxifloxacin had little effect against both M.
intracellulare and M. avium. Linezolid had modest activity whereas clofazimine
had little effect against M. avium. Most MAC isolates with non-susceptibility to
isepamicin were also non-susceptible to the other four aminoglycosides. Most
streptomycin-susceptible MAC isolates were also susceptible to amikacin.
Synergistic effect of combination of isepamicin and clofazimine was demonstrated
in all (100%) M. intracellulare isolates whereas in only 50% M. avium isolates.
CONCLUSION: When treating MAC diseases, species identification plays an important
role in choosing treatment regimens. Combination of isepamicin and clofazimine
may be a promising regimen in M. intracellulare-associated disease.
PMID- 28705771
TI - Different frequencies of Porphyromonas gingivalis infection in cancers of the
upper digestive tract.
AB - The high incidence rate of multiple carcinomas in the upper digestive tract is
often explained in terms of involvement of the same underlying risk factors. It
has been reported that the oral bacterium Streptococcus anginosus is associated
with esophageal, gastric, and pharyngeal cancers. We previously reported
occurrence of Porphyromonas gingivalis (P. gingivalis) DNA in esophagus cancer.
In this study, the presence of P. gingivalis in specimens of various types of
cancer from the upper digestive tract was investigated. Here we report that P.
gingivalis was preferentially and frequently present in specimens of esophageal
cancer as well as in those from dysplasia of the esophagus but rarely in matched
noncancerous portions and are quite low or absent in cancers from the cardia or
stomach. Therefore, it led us to propose that, the microorganism does not survive
in conditions of high acidity. We then investigate the pH dependence of survival
of P. gingivalis as well as the acid tolerance of it. We found that, exposure to
acidic buffers of a wide range of pH values led to a decline in colony forming
units of P. gingivalis, thus, providing a possible explanation for variations in
frequencies of P. gingivalis infection in this study.
PMID- 28705772
TI - Improving pharmacological targeting of AKT in melanoma.
AB - Targeting AKT with pharmacological agents inhibiting this protein in the melanoma
clinic is ineffective. This is a major contradiction considering the substantial
preclinical data suggesting AKT as an effective target. Various approaches have
been undertaken to unravel this contradiction and drug combinations sought that
could resolve this concern. We have shown that genetic targeting AKT3 or WEE1 can
be effective for inhibiting tumor growth in preclinical animal models. However,
no one has examined whether combining pharmacological agents targeting each of
these enzymes could be more effective than inhibiting each alone and enhance the
efficacy of targeting AKT in melanoma. This report shows that combining the AKT
inhibitors (AZD5363 or MK1775) with the WEE1 inhibitor, AZD5363, can
synergistically kill cultured melanoma cells and decrease melanoma tumor growth
by greater than 90%. Co-targeting AKT and WEE1 led to enhanced deregulation of
the cell cycle and DNA damage repair pathways by modulating the transcription
factors p53 and FOXM1, as well as the proteins whose expression is regulated by
these two proteins. Thus, this study identifies a unique combination of
pharmacological agents and the ratio needed for efficacy that could be used to
potentially improve the therapeutic effectiveness of targeting AKT in the clinic.
PMID- 28705773
TI - Recent progress in circular RNAs in human cancers.
AB - Circular RNAs (circRNAs) are a large class of endogenous RNAs, formed by exon
skipping or back-splicing events as covalently closed loops, which are expressed
abundantly in mammalian cells. Although their biological functions remain largely
unknown, recent studies show that circRNAs have three main functions in mammalian
cells. First, circRNAs can regulate transcription and RNA splicing. Second,
circRNAs function as microRNA (miRNA) sponges. Third, they can be translated into
protein driven by N6-methyladenosine modification. Taking advantage of RNA
sequencing (RNA-seq) technology, the expressions of circRNAs were found to be
dysregulated in all types of cancer cell lines, tumor tissues, and even plasma
samples from patients, which correlated with certain clinical characteristics,
suggesting the potential roles of circRNAs in tumor progression. Considering
their conserved sequences and stable structures, circRNAs were deemed to be
promising biomarkers for the early diagnosis and prognosis prediction of cancer.
In this review, we describe briefly the formation and properties of circRNAs, and
focus mainly on recent progress in research into their function, regulation, and
clinical relevance in different cancers.
PMID- 28705774
TI - American Spinal Injury Association A (sensory and motor complete) is not
different from American Spinal Injury Association B (sensory incomplete, motor
complete) in gunshot-related spinal cord injury.
AB - BACKGROUND CONTEXT: We receive a large number of patients with spinal cord injury
(SCI) due to penetrating gunshot wounds (GSW) at our national rehabilitation
center. Although many patients are labeled American Spinal Injury Association
(ASIA) B sensory incomplete because of sensory sparing, especially deep anal
pressure, with purported prognostic value, we have not observed a clinical
difference from patients labeled ASIA A complete. We hypothesized that sensory
sparing, if meaningful, should reduce the occurrence of pressure ulcers. PURPOSE:
To determine if ASIA classifications A and B are important distinctions for
patients with SCIs secondary to civilian gunshot wounds. DESIGN/SETTING: A
retrospective chart review was performed on all patients with civilian gunshot
induced SCI transferred to Rancho Los Amigos Rehabilitation Center between 1999
and 2014. Outcome measures were occurrence of pressure ulcers and surgical
intervention for pressure ulcers. PATIENT SAMPLE: We included a total of 487
patients who sustained civilian gunshot wounds to the spine and were provided
care at Rancho Los Amigos Rehabilitation Center from 2001 to 2014. OUTCOME
MEASURES: Occurrence of pressure ulcers and surgical intervention for pressure
ulcers among patients who suffered civilian-induced gunshot wounds to the spine.
METHODS: Retrospective chart review identified 487 SCIs due to gunshot wounds
that were treated at Rancho Los Amigos from 2001 to 2014. Injury characteristics
including ASIA classification, pressure ulcers, and pressure ulcer surgeries were
recorded. Comprehensive surgical data were obtained for all patients. Chart
reviews and telephone interviews were performed to determine the occurrence of
any pressure ulcers and pressure ulcer surgeries. Statistical analysis was
performed to compare data by spinal region and ASIA grade. There were no
conflicts of interest from any of the authors, and there was no funding obtained
for this study. RESULTS: There was no statistical difference for cervical ASIA A
versus ASIA B for the occurrence of pressure ulcers or the percentage requiring
surgery, nor for thoracic A versus B. When grouped, there was a statistically
higher occurrence of pressure ulcers in cervical A or B classification than in
thoracic A or B classification, but a higher rate of surgery for thoracic A or B
classification. Lumbosacral cauda equina levels were not statistically different
in occurrence of pressure ulcers or pressureulcer surgery by ASIA grades A-D.
Overall, when grouped C1-T12, cord-level cervicothoracic A and B classifications
were statistically equivalent. C1-T12 cord level C or D classification with motor
sparing had statistically lower occurrence and need of surgery for pressure
ulcers and were equivalent to lumbosacral cauda equina level A-D. CONCLUSION:
ASIA A and B distinctions are not meaningful at spinal cord levels in the
cervicothoracic spine due to gunshot wounds as shown by similar occurrence of
pressure ulcers and pressure ulcer surgery, and should be treated as if the same.
Meaningful decrease of pressure ulcers at cord levels does not occur until there
is motor sparing ASIA C or D. Furthermore, cauda equina lumbosacral injuries are
a lower risk, which is independent of ASIA grade A-D and statistically equivalent
to cord level C or D. Motor sparing at cord levels or any cauda equina level is
most determinative neurologically for the occurrence of pressure ulcers or
pressure ulcer surgery.
PMID- 28705775
TI - New cataract markers: Mechanisms of disease.
AB - Cataract is caused by nutritional, metabolic, environmental, and genetic factors,
and is a significant cause of blindness and visual impairment. In recent years,
extensive research into the human genome has revealed that numerous genetic
mutations are associated with cataract. These mutations affect a variety of
genes, including those encoding crystallin, membrane proteins, cytoskeletal
proteins, transcription factors, and metabolism-related proteins. Elucidation of
these mutations and the genetic and molecular mechanisms has helped clarify the
etiology of cataract and may facilitate its early diagnosis and treatment. This
review summarizes recent advances in our knowledge and potential clinical of
genetic markers of cataract.
PMID- 28705776
TI - Short- and medium-term biological variation estimates of leukocytes extended to
differential count and morphology-structural parameters (cell population data) in
blood samples obtained from healthy people.
AB - BACKGROUND: Recent studies showed that some cell population data (CPD) parameters
of neutrophils may be useful for diagnosing myelodysplastic syndromes and sepsis,
for the differential diagnosis of acute promyelocytic leukemia, and some CPD
parameters of lymphocytes may be a valuable tool for preliminary screening of B
cell lymphoproliferative disease. Notwithstanding the knowledge, no information
has been made available about their analytical quality specification. This study
was aimed to define short- and medium-term biological variation (BV) estimates
and reference change value (RCV) of leukocyte count, extended leukocyte
differential and CPD. METHODS: The study population consisted of 43 healthy
volunteers, who participated in the assessment of medium-term (21 volunteers;
blood sampling once a week for 5 consecutive weeks) and short-term (22
volunteers; blood sampling once a day for 5 consecutive days) BV, using Sysmex
XN. Outlier analysis was carried out before CV-ANOVA, to determine BV estimates
and their confidence intervals. RESULTS: The medium-term and short-term within
subject BV (CVI) was comprised between 0.6-19.7% and 0.2-21.9%, whereas the
medium-term and short-term between-subjects BV (CVG) was comprised between 1.2
61.5% and 1.1-58.5%. The RCVs were found to be similar for all the parameters, in
both arms of the study, except for some CPD parameters. CONCLUSION: This study
allowed accurately estimating the BV of many leukocyte parameters, some of which
have not been currently explored. The kinetics of some leukocyte turnover
suggests the use of short-term BV data for calculating analytical goals and RCV.
PMID- 28705777
TI - Treatment of Eagle syndrome with transcervical approach secondary to a failed
intraoral attempt: Surgical technique and literature review.
AB - The styloid or Eagle syndrome is characterized by recurrent episodes of
pharyngeal pain irradiating in various additional sites of head and neck, owing
to an elongated stylohyoid process or calcification of stylohyoid ligament or
complex. This article aimed to report a case of surgical treatment of Eagle
syndrome by applying transcervical approach for styloidectomy, after a previous
but failed intraoral attempt. Aside from the description of the surgical steps of
this technique, the current literature was reviewed too. Subsequently to the
operation, the patient cited significant resolution of symptomatology from the
first postoperative week and remained pain-free the following 6 months. After
this follow-up period, the esthetic outcome of the external scar was very
satisfactory, without other complications. If not properly diagnosed, patients
with Eagle syndrome may receive ineffective or unsuccessful treatments. Secondary
to failed intraoral attempt, which results in an elongated residual stump, it is
advisable to use transcervical approach for successful resection of the
stylohyoid process. In the presented case, the establishment of both adequate
exposure and control of neurovascular injury was preoperatively considered
essential for dissection in a previously operated field. The selection of either
transcervical or intraoral approach is a surgeon-dependent decision, which relies
on surgeon's experience, skills, and available equipment and may be influenced by
the patient's expectations. Despite the reported disadvantages of transcervical
approach, various modifications of this technique have lessened the possible
morbid consequences.
PMID- 28705778
TI - Maternal linuron exposure alters testicular development in male offspring rats at
the whole genome level.
AB - Linuron is a widely used herbicide; its toxicity on the male reproductive system
has been recognized. The current study was designed to explore the molecular
mechanism underlying linuron-induced reproductive toxicity. Pregnant rats
received daily oral gavage of linuron at the dose of 120mg/kg/d from gestation
day (GD)12 to GD17. Tissues from male offspring rats were collected for
pathological examination and microarray gene expression profiling. Changes in
gene expression were further verified by quantitative real-time RT-PCR. Data
showed that linuron-exposed offspring rats had a decreased sperm count (88% of
controls) and disrupted acrosome formation. There were evident damages in
seminiferous tubules and abnormal morphology in mesenchymal cells in samples from
linuron-exposed animals. Microarray analysis indicated that the expressions of
testosterone synthesis-associated genes, i.e., Star, P450scc, 3beta-Hsd, Abp,
Cox7a2, Pcna, p450c17and17beta-Hsd were significantly altered by linuron
exposure, along with other genes involving in cell proliferation and apoptosis,
such as c-myc, S6K, Apaf1, and TSC1. These data indicate that linuron upon
entering male offspring body can directly or indirectly interact with the
androgen production and function; linuron-induced alteration in genes encoding
testosterone synthesis is likely a major factor in linuron-induced male
reproductive toxicity.
PMID- 28705779
TI - Autoimmune aspects of psoriasis: Heritability and autoantigens.
AB - Chronic immune-mediated disorders (IMDs) constitute a major health burden.
Understanding IMD pathogenesis is facing two major constraints: Missing
heritability explaining familial clustering, and missing autoantigens.
Pinpointing IMD risk genes and autoimmune targets, however, is of fundamental
importance for developing novel causal therapies. The strongest association of
all IMDs is seen with human leukocyte antigen (HLA) alleles. Using psoriasis as
an IMD model this article reviews the pathogenic role HLA molecules may have
within the polygenic predisposition of IMDs. It concludes that disease-associated
HLA alleles account for both missing heritability and autoimmune mechanisms by
facilitating tissue-specific autoimmune responses through autoantigen
presentation.
PMID- 28705781
TI - Effects of Interleukin 17 on the cardiovascular system.
AB - Cardiovascular diseases remain the leading cause of death worldwide and account
for most of the premature mortality observed in chronic inflammatory diseases.
Common mechanisms underlie these two types of disorders, where the contribution
of Interleukin (IL)-17A, the founding member of the IL-17 family, is highly
suspected. While the local effects of IL-17A in inflammatory disorders have been
well described, those on the cardiovascular system remain less studied. This
review focuses on the effects of IL-17 on the cardiovascular system both on
isolated cells and in vivo. IL-17A acts on vessel and cardiac cells, leading to
inflammation, coagulation and thrombosis. In vivo and clinical studies have shown
its involvement in the pathogenesis of cardiovascular diseases including
atherosclerosis and myocardial infarction that occur prematurely in chronic
inflammatory disorders. As new therapeutic approaches are targeting the IL-17
pathway, this review should help to better understand their positive and negative
outcomes on the cardio-vascular system.
PMID- 28705780
TI - International consensus: What else can we do to improve diagnosis and therapeutic
strategies in patients affected by autoimmune rheumatic diseases (rheumatoid
arthritis, spondyloarthritides, systemic sclerosis, systemic lupus erythematosus,
antiphospholipid syndrome and Sjogren's syndrome)?: The unmet needs and the
clinical grey zone in autoimmune disease management.
AB - Autoimmune diseases are a complex set of diseases characterized by immune system
activation and, although many progresses have been done in the last 15years,
several unmet needs in the management of these patients may be still identified.
Recently, a panel of international Experts, divided in different working groups
according to their clinical and scientific expertise, were asked to identify,
debate and formulate a list of key unmet needs within the field of rheumatology,
serving as a roadmap for research as well as support for clinicians. After a
systematic review of the literature, the results and the discussions from each
working group were summarised in different statements. Due to the differences
among the diseases and their heterogeneity, a large number of statements was
produced and voted by the Experts to reach a consensus in a plenary session. At
all the steps of this process, including the initial discussions by the steering
committee, the identification of the unmet needs, the expansion of the working
group and finally the development of statements, a large agreement was attained.
This work confirmed that several unmet needs may be identified and despite the
development of new therapeutic strategies as well as a better understanding of
the effects of existing therapies, many open questions still remain in this
field, suggesting a research agenda for the future and specific clinical
suggestions which may allow physicians to better manage those clinical conditions
still lacking of scientific clarity.
PMID- 28705782
TI - Biologics in myelodysplastic syndrome-related systemic inflammatory and
autoimmune diseases: French multicenter retrospective study of 29 patients.
AB - BACKGROUND: Systemic inflammatory and autoimmune diseases (SIADs) associated with
myelodysplastic syndromes are often difficult to treat. Corticosteroids are
efficient but only usually at high doses. The use of biologics needs to be
specified. METHODS: In a French multicenter retrospective study, we analyzed the
efficacy and safety of biologics (tumor necrosis factor-alpha [TNF-alpha]
antagonists, tocilizumab, rituximab and anakinra) for SIADs associated with
myelodysplastic syndromes (MDSs). Clinical, biological and overall treatment
responses were evaluated. When several lines of treatment were used, data were
analyzed before and at the end of each treatment line and were pooled to compare
overall response among steroids, disease-modifying anti-rheumatic drugs (DMARDs)
and biologics. RESULTS: We included 29 patients (median age 67years
[interquartile range 62-76], 83% males) with MDS-related SIADs treated with at
least one biologic. The MDSs were predominantly refractory anemia with excess
blasts 1 (38%) and refractory cytopenia with multilineage dysplasia (21%). The
SIADs were mainly arthritis (n=6; 20%), relapsing polychondritis (n=8; 30%) and
vasculitis (n=10; 34%). During a 3-year median follow-up (IQR 1.3-4.5), a total
of 114 lines of treatments were used for all patients: steroids alone (22%),
DMARDs (23%), TNF-alpha antagonists (14%), anakinra (10%), rituximab (10%),
tocilizumab (7%) and azacytidine (9%). Considering all 114 lines, overall
response (complete and partial) was shown in 54% cases. Overall response was more
frequent with steroids (78%) and rituximab (66%) than DMARDs (45%) and other
biologics (33%) (p<0.05). Rituximab had better response in vasculitis and TNF
alpha antagonists in arthritis. During follow-up, 20 patients (71%) presented at
least one severe infection. CONCLUSION: This nationwide study demonstrates the
efficacy of steroids for SIAD-associated MDSs but a high frequency of steroid
dependence. The response to biologics seems low, but rituximab and azacytidine
seem promising.
PMID- 28705783
TI - Correction of Abdominal Distention by Biofeedback-Guided Control of
Abdominothoracic Muscular Activity in a Randomized, Placebo-Controlled Trial.
AB - BACKGROUND & AIMS: Abdominal distention is produced by abnormal somatic postural
tone. We developed an original biofeedback technique based on electromyography
guided control of abdominothoracic muscular activity. We performed a randomized,
placebo-controlled study to demonstrate the superiority of biofeedback to placebo
for the treatment of abdominal distention. METHODS: At a referral center in
Spain, we enrolled consecutive patients with visible abdominal distention who
fulfilled the Rome III criteria for functional intestinal disorders (47 women, 1
man; 21-74 years old); 2 patients assigned to the placebo group withdrew and 2
patients assigned to biofeedback were not valid for analysis. Abdominothoracic
muscle activity was recorded by electromyography. The patients in the biofeedback
group were shown the signal and instructed to control muscle activity, whereas
patients in the placebo received no instructions and were given oral simethicone.
Each patient underwent 3 sessions over a 10-day period. The primary outcomes were
subjective sensation of abdominal distention, measured by graphic rating scales
for 10 consecutive days before and after the intervention. RESULTS: Patients in
the biofeedback group effectively learned to reduce intercostal activity (by a
mean 45% +/- 3%), but not patients in the placebo group (reduced by a mean 5% +/-
2%; P < .001). Patients in the biofeedback group learned to increase anterior
wall muscle activity (by a mean 101% +/- 10%), but not in the placebo group
(decreased by a mean 4% +/- 2%; P < .001). Biofeedback resulted in a 56% +/- 1%
reduction of abdominal distention (from a mean score of 4.6 +/- 0.2 to 2.0 +/-
0.2), whereas patients in the placebo group had a reduction of only 13% +/- 8%
(from a mean score of 4.7 +/- 0.1 to 4.1 +/- 0.4) (P < .001). CONCLUSIONS: In a
randomized trial of patients with a functional intestinal disorder, we found that
abdominal distention can be effectively corrected by biofeedback-guided control
of abdominothoracic muscular activity, compared with placebo. ClincialTrials.gov
no: NCT01205100.
PMID- 28705784
TI - Laparoscopic proctocolectomy with ileal j-pouch anal anastomosis in children.
AB - BACKGROUND/AIMS: We aimed to evaluate postoperative fecal incontinence scales of
children who underwent laparoscopic proctocolectomy and ileal J-pouch anastomosis
for familial adenomateous polyposis (FAP) and inflammatory bowel disease (IBD).
MATERIALS AND METHODS: Fecal incontinence scores were collected at 3 months post
surgery. A retrospective chart review was also performed to obtain the
demographic data and operative technical details. RESULTS: The postoperative
Wexner Fecal Incontinence Score was 0 in 9 of 11 patients and satisfactory in the
remaining two. None of the children had a major complication. CONCLUSION: Even
though the presented study does not have any comparable data, it seems that
laparoscopic total proctocolectomy with ileal J-pouch anal anastomosis (TP IPAA)
might be the best choice of surgery because it provides good continence with low
complication rates.
PMID- 28705785
TI - Determination of certain bacterial groups in gut microbiota and endotoxin levels
in patients with nonalcoholic steatohepatitis.
AB - BACKGROUND/AIMS: In recent years, the role of the gut microbiota has emerged in
several diseases. Herein we aimed to determine the fecal microbiota, endotoxin
levels, and inflammation markers in patients with nonalcoholic steatohepatitis
(NASH) and healthy controls. MATERIALS AND METHODS: A total of 46 NASH patients
and 38 healthy controls were included. NASH patients were diagnosed according to
the steatosis, activity, and fibrosis score/fatty liver inhibition of progression
algorithm. 16S rRNA gene-targeted specific primers were used for quantification
of certain bacterial groups, and a plasmid library was constructed and sequenced
in order to determine dominant Lactobacillus and Bifidobacterium members in
patients and controls. RESULTS: Significantly decreased Akkermansia muciniphila
and increased Enterobacteriaceae levels were determined in patients compared to
healthy controls even after adjusting for the body mass index (BMI) and age.
Patients with >=F2 fibrosis had significantly higher Enterobacteriaceae levels
compared to F0-F1 fibrosis. Serum endotoxin and high-sensitivity C-reactive
protein levels were significantly higher in patients group. According to the
sequencing results, L. reuteri, which was one of the dominant Lactobacillus
species in the patient group, could not be detected in healthy controls.
Bifidobacterium infantis was found in the patients' feces but not in the
controls. CONCLUSION: We demonstrated a BMI and age-independent association
between the presence of NASH and levels of A. muciniphila and Enterobacteriaceae
as well as increased endotoxin levels. L. reuteri was abundant in the patient
group, suggesting that dominant Lactobacillus species should be considered before
probiotic treatments.
PMID- 28705786
TI - Investigation of the efficacy of synbiotics in the treatment of functional
constipation in children: a randomized double-blind placebo-controlled study.
AB - BACKGROUND/AIMS: The aim of this study was to demonstrate the efficacy of
synbiotic (Lactobacillus casei, L. rhamnosus, L. plantarum, and Bifidobacterium
lactis and prebiotics [fiber, polydextrose, fructo-oligosaccharides, and galacto
oligosaccharides]) treatment in children with functional constipation. MATERIALS
AND METHODS: This study was performed in patients aged 4-18 years, and the
patients were diagnosed to have functional constipation according to the Roma III
diagnostic criteria. In this prospective study, the first group received
synbiotic and the second group received a placebo. At the end of 4 weeks,
patients were questioned about the initial symptoms. Patients who showed
improvement in the initial symptoms at the end of the 4-week treatment period
were considered to completely benefit from the treatment and those with some
improvement in initial symptom were considered to partially benefit from the
treatment. RESULTS: The synbiotic and placebo groups comprised 72 and 74
patients, respectively. The mean age in the whole study group was 9.18+/-3.48
years with a male:female ratio of 1:21. After 4 weeks of treatment, significant
improvement was not observed in any of the findings in the placebo group.
Conversely, a significant improvement was observed in the weekly number of
defecations, abdominal pain, painful defecation, and pediatric Bristol scale
(p<=0.001) in the synbiotic group. Complete benefit from the treatment was
achieved in 48 (66.7%) and 21 (28.3%) patients in the synbiotic and placebo
groups, respectively, and a significant difference was observed between the
groups (p<=0.001). CONCLUSION: Our studies have shown that the use of synbiotics
in the treatment of functional constipation in children is beneficial.
PMID- 28705787
TI - A rare cause of gastric outlet obstruction.
PMID- 28705788
TI - How Do Clinicians Learn About Knowledge Translation? An Investigation of Current
Web-Based Learning Opportunities.
AB - BACKGROUND: Clinicians are important stakeholders in the translation of well
designed research evidence into clinical practice for optimal patient care.
However, the application of knowledge translation (KT) theories and processes may
present conceptual and practical challenges for clinicians. Online learning
platforms are an effective means of delivering KT education, providing an
interactive, time-efficient, and affordable alternative to face-to-face education
programs. OBJECTIVE: This study investigates the availability and accessibility
of online KT learning opportunities for health professionals. It also provides an
analysis of the types of resources and associated disciplines retrieved by a
range of KT synonyms. METHODS: We searched a range of bibliographic databases and
the Internet (Google advanced option) using 9 KT terms to identify online KT
learning resources. To be eligible, resources had to be free, aimed at
clinicians, educational in intent, and interactive in design. Each term was
searched using two different search engines. The details of the first 100
websites captured per browser (ie, n=200 results per term) were entered into
EndNote. Each site was subsequently visited to determine its status as a learning
resource. Eligible websites were appraised for quality using the AACODS
(Authority, Accuracy, Coverage, Objectivity, Date, Significance) tool. RESULTS:
We identified 971 unique websites via our multiple search strategies. Of these,
43 were health-related and educational in intent. Once these sites were evaluated
for interactivity, a single website matched our inclusion criteria (Dementia
Knowledge Translation Learning Centre). CONCLUSIONS: KT is an important but
complex system of processes. These processes overlap with knowledge, practice,
and improvement processes that go by a range of different names. For clinicians
to be informed and competent in KT, they require better access to free learning
opportunities. These resources should be designed from the viewpoint of the
clinician, presenting KT's multifaceted theories and processes in an engaging,
interactive way. This learning should empower clinicians to contextualize and
apply KT strategies within their own care settings.
PMID- 28705789
TI - Treatment of Peritoneal Dissemination in Stomach Cancer Patients With
Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (HIPEC):
Rationale and Design of the PERISCOPE Study.
AB - BACKGROUND: Patients with gastric cancer and peritoneal carcinomatosis have a
very poor prognosis; median survival is 3 to 4 months. Palliative systemic
chemotherapy is currently the only treatment available in the Netherlands.
Intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC) has an
established role in the treatment of peritoneal carcinomatosis originating from
colorectal cancer, appendiceal cancer, and pseudomyxoma peritonei; its role in
gastric cancer is uncertain. Currently, there is no consensus on the choice of
chemotherapeutic agents used in HIPEC for gastric cancer. OBJECTIVE: The main
objectives of this study are (1) to investigate the safety, tolerability, and
feasibility of gastrectomy combined with cytoreductive surgery and HIPEC after
systemic chemotherapy, as a primary treatment option for patients with advanced
gastric cancer with tumor positive peritoneal cytology and/or limited peritoneal
carcinomatosis; and (2) to determine the maximum tolerated dose (MTD) of
intraperitoneal docetaxel in combination with a fixed dose of intraperitoneal
oxaliplatin. METHODS: The PERISCOPE study is a multicenter, open label, phase I
II dose-escalation study. The MTD of docetaxel will be studied using a 3+3
design. Patients with locally advanced (cT3-cT4) gastric adenocarcinoma are
eligible for inclusion if the primary gastric tumor is considered resectable,
tumor positive peritoneal cytology and/or limited peritoneal carcinomatosis is
confirmed by diagnostic laparoscopy/ laparotomy, and prior systemic chemotherapy
was without disease progression. At laparotomy, cytoreductive surgery (complete
removal of all macroscopically visible tumor deposits) and a total or partial
gastrectomy with a D2 lymph node dissection is performed. An open HIPEC technique
is used with 460mg/m2 hyperthermic oxaliplatin for 30 minutes (41 degrees C to 42
degrees C) followed by normothermic docetaxel for 90 minutes (37 degrees C) in a
dose that will be escalated per 3 patients (0, 50, 75, 100, 125, 150 mg/m2). The
primary endpoint is treatment related toxicity. RESULTS: Patient accrual is
ongoing and the first results are expected in 2017. CONCLUSIONS: The PERISCOPE
study will determine the safety, tolerability, and feasibility of gastrectomy
combined with cytoreduction and HIPEC using oxaliplatin in combination with
docetaxel after systemic chemotherapy as primary treatment option for gastric
cancer patients with tumor positive peritoneal cytology and/or limited peritoneal
carcinomatosis. This study will provide pharmacokinetic data on the
intraperitoneal administration of oxaliplatin and docetaxel, including the MTD of
intraperitoneal-administered docetaxel. These data are a prerequisite for the
safe conduct of future HIPEC studies in patients with gastric cancer. TRIAL
REGISTRATION: Netherlands Trial Registration (NTR): NTR4250;
http://www.trialregister.nl/trialreg/admin/ rctview.asp?TC=4250 (Archived by
WebCite at http://www.webcitation.org/6rWJONgkt).
PMID- 28705790
TI - Children with life-limiting conditions in paediatric intensive care units: a
national cohort, data linkage study.
AB - OBJECTIVE: To determine how many children are admitted to paediatric intensive
care unit (PICU) with life-limiting conditions (LLCs) and their outcomes. DESIGN:
National cohort, data-linkage study. SETTING: PICUs in England. PATIENTS:
Children admitted to a UK PICU (1 January 2004 and 31 March 2015) were identified
in the Paediatric Intensive Care Audit Network dataset. Linkage to hospital
episodes statistics enabled identification of children with a LLC using an
International Classification of Diseases (ICD10) code list. MAIN OUTCOME
MEASURES: Random-effects logistic regression was undertaken to assess risk of
death in PICU. Flexible parametric survival modelling was used to assess survival
in the year after discharge. RESULTS: Overall, 57.6% (n=89 127) of PICU
admissions and 72.90% (n=4821) of deaths in PICU were for an individual with a
LLC.The crude mortality rate in PICU was 5.4% for those with a LLC and 2.7% of
those without a LLC. In the fully adjusted model, children with a LLC were 75%
more likely than those without a LLC to die in PICU (OR 1.75 (95% CI 1.64 to
1.87)).Although overall survival to 1 year postdischarge was 96%, children with a
LLC were 2.5 times more likely to die in that year than children without a LLC
(OR 2.59 (95% CI 2.47 to 2.71)). CONCLUSIONS: Children with a LLC accounted for a
large proportion of the PICU population. There is an opportunity to integrate
specialist paediatric palliative care services with paediatric critical care to
enable choice around place of care for these children and families.
PMID- 28705791
TI - Lack of evidence for debriefing after terrorist attacks.
PMID- 28705792
TI - Deletion of Fstl1 (Follistatin-Like 1) From the Endocardial/Endothelial Lineage
Causes Mitral Valve Disease.
AB - OBJECTIVE: Fstl1 (Follistatin-like 1) is a secreted protein that is expressed in
the atrioventricular valves throughout embryonic development, postnatal
maturation, and adulthood. In this study, we investigated the loss of Fstl1 in
the endocardium/endothelium and their derived cells. APPROACH AND RESULTS: We
conditionally ablated Fstl1 from the endocardial lineage using a transgenic Tie2
Cre mouse model. These mice showed a sustained Bmp and Tgfbeta signaling after
birth. This resulted in ongoing proliferation and endocardial-to-mesenchymal
transition and ultimately in deformed nonfunctional mitral valves and a
hypertrophic dilated heart. Echocardiographic and electrocardiographic analyses
revealed that loss of Fstl1 leads to mitral regurgitation and left ventricular
diastolic dysfunction. Cardiac function gradually deteriorated resulting in heart
failure with preserved ejection fraction and death of the mice between 2 and 4
weeks after birth. CONCLUSIONS: We report on a mouse model in which deletion of
Fstl1 from the endocardial/endothelial lineage results in deformed mitral valves,
which cause regurgitation, heart failure, and early cardiac death. The findings
provide a potential molecular target for the clinical research into myxomatous
mitral valve disease.
PMID- 28705793
TI - Dachsous1-Fat4 Signaling Controls Endothelial Cell Polarization During Lymphatic
Valve Morphogenesis-Brief Report.
AB - OBJECTIVE: The purpose of this study was to investigate the role of Fat4 and
Dachsous1 signaling in the lymphatic vasculature. APPROACH AND RESULTS:
Phenotypic analysis of the lymphatic vasculature was performed in mice lacking
functional Fat4 or Dachsous1. The overall architecture of lymphatic vasculature
is unaltered, yet both genes are specifically required for lymphatic valve
morphogenesis. Valve endothelial cells (Prox1high [prospero homeobox protein 1]
cells) are disoriented and failed to form proper valve leaflets. Using Lifeact
GFP (green fluorescent protein) mice, we revealed that valve endothelial cells
display prominent actin polymerization. Finally, we showed the polarized
recruitment of Dachsous1 to membrane protrusions and cellular junctions of valve
endothelial cells in vivo and in vitro. CONCLUSIONS: Our data demonstrate that
Fat4 and Dachsous1 are critical regulators of valve morphogenesis. This study
highlights that valve defects may contribute to lymphedema in Hennekam syndrome
caused by Fat4 mutations.
PMID- 28705794
TI - Targeted Disruption of JCAD (Junctional Protein Associated With Coronary Artery
Disease)/KIAA1462, a Coronary Artery Disease-Associated Gene Product, Inhibits
Angiogenic Processes In Vitro and In Vivo.
AB - OBJECTIVE: Recent genome-wide association studies newly identified the human
KIAA1462 gene as a new locus for coronary artery disease. However, the function
of the gene product, named JCAD (junctional protein associated with coronary
artery disease), is unknown. Because JCAD is expressed at cell-cell junctions in
endothelial cells, we hypothesized and tested whether JCAD regulates angiogenic
processes in vitro and in vivo. APPROACH AND RESULTS: Cell culture experiments
revealed impaired angiogenic ability (proliferation, migration, and cord
formation) by the knockdown of JCAD with siRNA (P<0.05 versus control siRNA). We
have generated mice lacking JCAD (mKIAA1462-/-) by gene-targeted deletion of JCAD
to address in vivo angiogenic function. mKIAA1462-/- mice did not show
morphological differences in development of retinal vasculature. Ex vivo aortic
ring model demonstrated impaired neovascularization in aorta from mKIAA1462-/-
mice than control wild-type mice (P<0.05). Tumor growth was assessed by
monitoring tumor volume after the subcutaneous injection of melanoma, LLC (Lewis
lung carcinoma), and E0771 cells into the mice. mKIAA1462-/- mice exhibited
significantly smaller tumor volume compared with wild-type mice (P<0.001).
Histological assessment of the tumor exhibited less smooth muscle actin-positive
neovascularization determined by CD31-positive vascular structure in tumor of
mKIAA1462-/- mice than wild-type mice, indicating that knockdown of JCAD
inhibited the vascular maturation in pathological angiogenic process.
CONCLUSIONS: These in vitro and in vivo studies suggest that JCAD has a redundant
functional role in physiological angiogenesis but serves a pivotal role in
pathological angiogenic process after birth.
PMID- 28705795
TI - Selective Deletion of Leptin Signaling in Endothelial Cells Enhances Neointima
Formation and Phenocopies the Vascular Effects of Diet-Induced Obesity in Mice.
AB - OBJECTIVE: Obesity is associated with elevated circulating leptin levels and
hypothalamic leptin resistance. Leptin receptors (LepRs) are expressed on
endothelial cells, and leptin promotes neointima formation in a receptor
dependent manner. Our aim was to examine the importance of endothelial LepR
(End.LepR) signaling during vascular remodeling and to determine whether the
cardiovascular consequences of obesity are because of hyperleptinemia or
endothelial leptin resistance. APPROACH AND RESULTS: Mice with loxP-flanked LepR
alleles were mated with mice expressing Cre recombinase controlled by the
inducible endothelial receptor tyrosine kinase promoter. Obesity was induced with
high-fat diet. Neointima formation was examined after chemical carotid artery
injury. Morphometric quantification revealed significantly greater intimal
hyperplasia, neointimal cellularity, and proliferation in End.LepR knockout mice,
and similar findings were obtained in obese, hyperleptinemic End.LepR wild-type
animals. Analysis of primary endothelial cells confirmed abrogated signal
transducer and activator of transcription-3 phosphorylation in response to leptin
in LepR knockout and obese LepR wild-type mice. Quantitative PCR, ELISA, and
immunofluorescence analyses revealed increased expression and release of
endothelin-1 in End.LepR-deficient and LepR-resistant cells, and ET receptor A/B
antagonists abrogated their paracrine effects on murine aortic smooth muscle cell
proliferation. Reduced expression of peroxisome proliferator-activated receptor
gamma and increased nuclear activator protein-1 staining was observed in End.LepR
deficient and LepR-resistant cells, and peroxisome proliferator-activated
receptor-gamma antagonization increased endothelial endothelin-1 expression.
CONCLUSIONS: Our findings suggest that intact endothelial leptin signaling limits
neointima formation and that obesity represents a state of endothelial leptin
resistance. These observations and the identification of endothelin-1 as soluble
mediator of the cardiovascular risk factor obesity may have relevant therapeutic
implications.
PMID- 28705797
TI - Cyclical Cushing's: how best to catch the ups and downs.
AB - A 68-year-old man with a background of hypertension and type 2 diabetes presented
with fluctuating symptoms of muscle aches and pains and tiredness. His initial
work-up for the possibility of hypercortisolaemia showed a completely variable
pattern, with 24-hour cortisol excretion and serum cortisol post 1 mg
dexamethasone suppression test ranging from normal to significantly elevated. A
series of salivary cortisol with symptom diary confirmed the cyclical nature of
hypercortisolaemia, and his concomitant adrenocorticotropic hormone (ACTH) levels
were elevated. An inferior petrosal sinus sampling, performed during
hypercortisolaemic phase of his cycle,suggested a central source of ACTH
secretion. He had unsuccessful exploration of his pituitary and was eventually
treated with bilateral adrenalectomy followed by lifelong steroid replacement.
His symptoms improved immediately, and he came off his oral hypoglycaemic and
antihypertensive agents within 6 months following his surgery.
PMID- 28705796
TI - Tracking Adventitial Fibroblast Contribution to Disease: A Review of Current
Methods to Identify Resident Fibroblasts.
AB - Cells present in the adventitia, or outermost layer of the blood vessel,
contribute to the progression of vascular diseases, such as atherosclerosis,
hypertension, and aortic dissection. The adventitial fibroblast of the aorta is
the prototypic perivascular fibroblast, but the adventitia is composed of
multiple distinct cell populations. Therefore, methods for uniquely identifying
the fibroblast are critical for a better understanding of how these cells
contribute to disease processes. A popular method for distinguishing adventitial
cell types relies on the use of genetic tools in the mouse to trace and
manipulate these cells. Because lineage tracing relying on Cre-recombinase
expressing mice is used more frequently in studies of vascular disease, it is
important to outline the advantages and limitations of these genetic tools. The
purpose of this article is to provide an overview of the various genetic tools
available in the mouse for the study of resident adventitial fibroblasts.
PMID- 28705798
TI - A mass obstructing mechanical prosthetic heart valve: thrombus or pannus?
PMID- 28705799
TI - Rapid developing empyema by group F beta Streptococcus anginosus group.
AB - A 43-year-old male had progressive pleuritic left-sided chest tightness with
shortness of breath. He had dental caries and tenderness on palpation of the left
lateral chest. Complete blood count showed leucocytosis. CT scan of the chest
with pulmonary emboli protocol showed multiple pulmonary nodules and nodular
pleural thickening at left posterior lateral pleura. Forty-eight hours post CTPE
scan, CT scan of the chest, abdomen and pelvis displayed right lower lobe
consolidation and left-sided pleural effusion with superimposed compressive
atelectasis. Ceftaroline intravenous was initiated, with CT-guided pigtail chest
tube insertion. Pleural fluid later grew group F beta-haemolytic Streptococcus
anginosus Patient improved significantly and was discharged 11 days later with
intravenous ertapenem. Patients with group F beta-haemolytic streptococci should
be managed aggressively with early and accurate diagnosis, antibiotics, drainage
and possible surgery.
PMID- 28705800
TI - Congenital kinking of aorta.
AB - Pseudocoarctation is an unusual anomaly mirroring true coarctation. Congenital
kinking or pseudocoarctation of aorta was never a benign condition. Although
surgical repair should be suggested for all symptomatic individuals. Regular
follow-up is obligatory for all asymptomatic patients deprived of linked
anomalies. We suggest CT-aortogram as a non-invasive imaging modality for the
definitive diagnosis of pseudocoarctation.
PMID- 28705801
TI - The miR-15 family reinforces the transition from proliferation to differentiation
in pre-B cells.
AB - Precursor B lymphocytes expand upon expression of a pre-B cell receptor (pre
BCR), but then transit into a resting state in which immunoglobulin light chain
gene recombination is initiated. This bi-phasic sequence is orchestrated by the
IL-7 receptor (IL-7R) and pre-BCR signaling, respectively, but little is known
about microRNAs fine-tuning these events. Here, we show that pre-B cells lacking
miR-15 family functions exhibit prolonged proliferation due to aberrant
expression of the target genes cyclin E1 and D3. As a consequence, they fail to
trigger the transcriptional reprogramming normally accompanying their
differentiation, resulting in a developmental block at the pre-B cell stage.
Intriguingly, our data indicate that the miR-15 family is suppressed by both IL
7R and pre-BCR signaling, suggesting it is actively integrated into the
regulatory circuits of developing B cells. These findings identify the miR-15
family as a novel element required to promote the switch from pre-B cell
proliferation to differentiation.
PMID- 28705802
TI - New international Turner syndrome guideline: a multi-society feat.
PMID- 28705803
TI - Clinical practice guidelines for the care of girls and women with Turner
syndrome: proceedings from the 2016 Cincinnati International Turner Syndrome
Meeting.
AB - Turner syndrome affects 25-50 per 100,000 females and can involve multiple organs
through all stages of life, necessitating multidisciplinary approach to care.
Previous guidelines have highlighted this, but numerous important advances have
been noted recently. These advances cover all specialty fields involved in the
care of girls and women with TS. This paper is based on an international effort
that started with exploratory meetings in 2014 in both Europe and the USA, and
culminated with a Consensus Meeting held in Cincinnati, Ohio, USA in July 2016.
Prior to this meeting, five groups each addressed important areas in TS care: 1)
diagnostic and genetic issues, 2) growth and development during childhood and
adolescence, 3) congenital and acquired cardiovascular disease, 4) transition and
adult care, and 5) other comorbidities and neurocognitive issues. These groups
produced proposals for the present guidelines. Additionally, four pertinent
questions were submitted for formal GRADE (Grading of Recommendations,
Assessment, Development and Evaluation) evaluation with a separate systematic
review of the literature. These four questions related to the efficacy and most
optimal treatment of short stature, infertility, hypertension, and hormonal
replacement therapy. The guidelines project was initiated by the European Society
for Endocrinology and the Pediatric Endocrine Society, in collaboration with The
European Society for Pediatric Endocrinology, The Endocrine Society, European
Society of Human Reproduction and Embryology, The American Heart Association, The
Society for Endocrinology, and the European Society of Cardiology. The guideline
has been formally endorsed by the European Society for Endocrinology, the
Pediatric Endocrine Society, the European Society for Pediatric Endocrinology,
the European Society of Human Reproduction and Embryology and the Endocrine
Society. Advocacy groups appointed representatives who participated in pre
meeting discussions and in the consensus meeting.
PMID- 28705804
TI - Loss of nitric oxide-mediated inhibition of purine neurotransmitter release in
the colon in the absence of interstitial cells of Cajal.
AB - Regulation of colonic motility depends on the integrity of enteric inhibitory
neurotransmission mediated by nitric oxide (NO), purine neurotransmitters, and
neuropeptides. Intramuscular interstitial cells of Cajal (ICC-IM) and platelet
derived growth factor receptor-alpha-positive (PDGFRalpha+) cells are involved in
generating responses to NO and purine neurotransmitters, respectively. Previous
studies have suggested a decreased nitrergic and increased purinergic
neurotransmission in KitW/KitW-v (W/Wv ) mice that display lesions in ICC-IM
along the gastrointestinal tract. However, contributions of NO to these
phenotypes have not been evaluated. We used small-chamber superfusion assays and
HPLC to measure the spontaneous and electrical field stimulation (EFS)-evoked
release of nicotinamide adenine dinucleotide (NAD+)/ADP-ribose, uridine adenosine
tetraphosphate (Up4A), adenosine 5'-triphosphate (ATP), and metabolites from the
tunica muscularis of human, monkey, and murine colons and circular muscle of
monkey colon, and we tested drugs that modulate NO levels or blocked NO
receptors. NO inhibited EFS-evoked release of purines in the colon via
presynaptic neuromodulation. Colons from W/Wv, Nos1-/- , and Prkg1-/- mice
displayed augmented neural release of purines that was likely due to altered
nitrergic neuromodulation. Colons from W/Wv mice demonstrated decreased nitrergic
and increased purinergic relaxations in response to nerve stimulation. W/Wv mouse
colons demonstrated reduced Nos1 expression and reduced NO release. Our results
suggest that enhanced purinergic neurotransmission may compensate for the loss of
nitrergic neurotransmission in muscles with partial loss of ICC. The interactions
between nitrergic and purinergic neurotransmission in the colon provide novel
insight into the role of neurotransmitters and effector cells in the neural
regulation of gastrointestinal motility.NEW & NOTEWORTHY This is the first study
investigating the role of nitric oxide (NO) and intramuscular interstitial cells
of Cajal (ICC-IM) in modulating neural release of purines in colon. We found that
NO inhibited release of purines in human, monkey, and murine colons and that
colons from KitW/KitW-v (W/Wv ) mice, which present with partial loss of ICC-IM,
demonstrated augmented neural release of purines. Interactions between nitrergic
and purinergic neurotransmission may affect motility in disease conditions with
ICC-IM deficiencies.
PMID- 28705805
TI - Validation and characterization of a novel method for selective vagal
deafferentation of the gut.
AB - There is a lack of tools that selectively target vagal afferent neurons (VAN)
innervating the gut. We use saporin (SAP), a potent neurotoxin, conjugated to the
gastronintestinal (GI) hormone cholecystokinin (CCK-SAP) injected into the nodose
ganglia (NG) of male Wistar rats to specifically ablate GI-VAN. We report that
CCK-SAP ablates a subpopulation of VAN in culture. In vivo, CCK-SAP injection
into the NG reduces VAN innervating the mucosal and muscular layers of the
stomach and small intestine but not the colon, while leaving vagal efferent
neurons intact. CCK-SAP abolishes feeding-induced c-Fos in the NTS, as well as
satiation by CCK or glucagon like peptide-1 (GLP-1). CCK-SAP in the NG of mice
also abolishes CCK-induced satiation. Therefore, we provide multiple lines of
evidence that injection of CCK-SAP in NG is a novel selective vagal
deafferentation technique of the upper GI tract that works in multiple vertebrate
models. This method provides improved tissue specificity and superior separation
of afferent and efferent signaling compared with vagotomy, capsaicin, and
subdiaphragmatic deafferentation.NEW & NOTEWORTHY We develop a new method that
allows targeted lesioning of vagal afferent neurons that innervate the upper GI
tract while sparing vagal efferent neurons. This reliable approach provides
superior tissue specificity and selectivity for vagal afferent over efferent
targeting than traditional approaches. It can be used to address questions about
the role of gut to brain signaling in physiological and pathophysiological
conditions.
PMID- 28705806
TI - Roles of autophagy and metabolism in pancreatic cancer cell adaptation to
environmental challenges.
AB - Pancreatic ductal adenocarcinoma (PDAC) displays extensive and poorly
vascularized desmoplastic stromal reaction, and therefore, pancreatic cancer
(PaCa) cells are confronted with nutrient deprivation and hypoxia. Here, we
investigate the roles of autophagy and metabolism in PaCa cell adaptation to
environmental stresses, amino acid (AA) depletion, and hypoxia. It is known that
in healthy cells, basal autophagy is at a low level, but it is greatly activated
by environmental stresses. By contrast, we find that in PaCa cells, basal
autophagic activity is relatively high, but AA depletion and hypoxia activate
autophagy only weakly or not at all, due to their failure to inhibit mechanistic
target of rapamycin. Basal, but not stress-induced, autophagy is necessary for
PaCa cell proliferation, and AA supply is even more critical to maintain PaCa
cell growth. To gain insight into the underlying mechanisms, we analyzed the
effects of autophagy inhibition and AA depletion on PaCa cell metabolism. PaCa
cells display mixed oxidative/glycolytic metabolism, with oxidative
phosphorylation (OXPHOS) predominant. Both autophagy inhibition and AA depletion
dramatically decreased OXPHOS; furthermore, pharmacologic inhibitors of OXPHOS
suppressed PaCa cell proliferation. The data indicate that the maintenance of
OXPHOS is a key mechanism through which autophagy and AA supply support PaCa cell
growth. We find that the expression of oncogenic activation mutation in GTPase
Kras markedly promotes basal autophagy and stimulates OXPHOS through an autophagy
dependent mechanism. The results suggest that approaches aimed to suppress
OXPHOS, particularly through limiting AA supply, could be beneficial in treating
PDAC.NEW & NOTEWORTHY Cancer cells in the highly desmoplastic pancreatic ductal
adenocarcinoma confront nutrient [i.e., amino acids (AA)] deprivation and
hypoxia, but how pancreatic cancer (PaCa) cells adapt to these conditions is
poorly understood. This study provides evidence that the maintenance of
mitochondrial function, in particular, oxidative phosphorylation (OXPHOS), is a
key mechanism that supports PaCa cell growth, both in normal conditions and under
the environmental stresses. OXPHOS in PaCa cells critically depends on autophagy
and AA supply. Furthermore, the oncogenic activation mutation in GTPase Kras
upregulates OXPHOS through an autophagy-dependent mechanism.
PMID- 28705807
TI - Augmentation of cGMP/PKG pathway and colonic motility by hydrogen sulfide.
AB - Hydrogen sulfide (H2S), like nitric oxide (NO), causes smooth muscle relaxation,
but unlike NO, does not stimulate soluble guanylyl cyclase (sGC) activity and
generate cyclic guanosine 5'-monophosphate (cGMP). The aim of this study was to
investigate the interplay between NO and H2S in colonic smooth muscle. In colonic
smooth muscle from rabbit, mouse, and human, l-cysteine, substrate of
cystathionine-gamma-lyase (CSE), or NaHS, an H2S donor, inhibited
phosphodiesterase 5 (PDE5) activity and augmented the increase in cGMP levels,
IP3 receptor phosphorylation at Ser1756 (measured as a proxy for PKG activation),
and muscle relaxation in response to NO donor S-nitrosoglutathione (GSNO),
suggesting augmentation of cGMP/PKG pathway by H2S. The inhibitory effect of l
cysteine, but not NaHS, on PDE5 activity was blocked in cells transfected with
CSE siRNA or treated with CSE inhibitor d,l-propargylglycine (dl-PPG), suggesting
activation of CSE and generation of H2S in response to l-cysteine. H2S levels
were increased in response to l-cysteine, and the effect of l-cysteine was
augmented by GSNO in a cGMP-dependent protein kinase-sensitive manner, suggesting
augmentation of CSE/H2S by cGMP/PKG pathway. As a result, GSNO-induced relaxation
was inhibited by dl-PPG. In flat-sheet preparation of colon, l-cysteine augmented
calcitonin gene-related peptide release in response to mucosal stimulation, and
in intact segments, l-cysteine increased the velocity of pellet propulsion. These
results demonstrate that in colonic smooth muscle, there is a novel interplay
between NO and H2S. NO generates H2S via cGMP/PKG pathway, and H2S, in turn,
inhibits PDE5 activity and augments NO-induced cGMP levels. In the intact colon,
H2S promotes colonic transit.NEW & NOTEWORTHY Hydrogen sulfide (H2S) and nitric
oxide (NO) are important regulators of gastrointestinal motility. The studies
herein provide the cross talk between NO and H2S signaling to mediate smooth
muscle relaxation and colonic transit. H2S inhibits phosphodiesterase 5 activity
to augment cGMP levels in response to NO, which, in turn, via cGMP/PKG pathway,
generates H2S. These studies suggest that interventions targeted at restoring NO
and H2S homeostasis within the smooth muscle may provide novel therapeutic
approaches to mitigate motility disorders.
PMID- 28705808
TI - Molecular Basis of Altered hERG1 Channel Gating Induced by Ginsenoside Rg3.
AB - Outward current conducted by human ether-a-go-go-related gene type 1 (hERG1)
channels is a major determinant of action potential repolarization in the human
ventricle. Ginsenoside 20(S)-Rg3 [Rg3; (2S,3R,4S,5S,6R)-2-[(2R,3R,4S,5S,6R)-4,5
dihydroxy-2-[[(3S,5R,8R,9R,10R,12R,13R,14R,17S)-12-hydroxy-17-[(2S)-2-hydroxy-6
methylhept-5-en-2-yl]-4,4,8,10,14-pentamethyl-2,3,5,6,7,9,11,12,13,15,16,17
dodecahydro-1H-cyclopenta[a]phenanthren-3-yl]oxy]-6-(hydroxymethyl)oxan-3-yl]oxy
6-(hydroxymethyl)oxane-3,4,5-triol], an alkaloid isolated from the root of Panax
ginseng, slows the rate of hERG1 deactivation, induces channels to open at more
negative potentials than normal, and increases current magnitude. The onset of
Rg3 action is extremely fast, suggesting that it binds to an extracellular
accessible site on the channel to alter its gating. Here we used a scanning
mutagenesis approach to identify residues in the extracellular loops and
transmembrane segments of hERG1 that might interact with Rg3. Single or multiple
residues of hERG1 were mutated to Ala or Cys and the resulting mutant channels
were heterologously expressed in Xenopus oocytes. The effects of Rg3 on the
voltage dependence of activation and the deactivation rate of mutant channel
currents were characterized using the two-microelectrode voltage clamp technique.
Mutation to Ala of specific residues in the S1 (Tyr420), S2 (Leu452, Phe463), and
S4 (Ile521, Lys525) segments partially inhibited the effects of Rg3 on hERG1. The
double mutant Y420A/L452A nearly eliminated the effects of Rg3 on voltage
dependent channel gating but did not prevent the increase in current magnitude.
These findings together with molecular modeling suggest that Rg3 alters the
gating of hERG1 channels by interacting with and stabilizing the voltage sensor
domain in an activated state.
PMID- 28705809
TI - The oncogenic role of the spliced somatostatin receptor sst5TMD4 variant in
prostate cancer.
AB - sst5TMD4, a splice variant of the sst5 gene, is overexpressed and associated with
aggressiveness in various endocrine-related tumors, but its presence, functional
role, and mechanisms of actions in prostate cancer (PCa)-the most common cancer
type in males-is completely unexplored. In this study, formalin-fixed, paraffin
embedded prostate pieces from patients with localized PCa, which included tumoral
and nontumoral adjacent regions (n = 45), fresh biopsies from patients with high
risk PCa (n = 52), and healthy fresh prostates from cystoprostatectomies (n = 14)
were examined. In addition, PCa cell lines and xenograft models were used to
determine the presence and functional role of sst5TMD4. Results demonstrated that
sst5TMD4 is overexpressed (mRNA/protein) in PCa samples, and this is especially
drastic in metastatic and/or high Gleason score tumor samples. Remarkably,
sst5TMD4 expression was associated with an altered frequency of 2 single
nucleotide polymorphisms: rs197055 and rs12599155. In addition, PCa cell lines
and xenograft models were used to demonstrate that sst5TMD4 overexpression
increases cell proliferation and migration in PCa cells and induces larger tumors
in nude mice, whereas its silencing decreased proliferation and migration.
Remarkably, sst5TMD4 overexpression activated multiple intracellular pathways
(ERK/JNK, MYC/MAX, WNT, retinoblastoma), altered oncogenes and tumor suppressor
gene expression, and disrupted the normal response to somatostatin analogs in PCa
cells. Altogether, we demonstrate that sst5TMD4 is overexpressed in PCa,
especially in those patients with a worse prognosis, and plays an important
pathophysiologic role in PCa, which suggesting its potential as a biomarker
and/or therapeutic target.-Hormaechea-Agulla, D., Jimenez-Vacas, J. M., Gomez
Gomez, E., L.-Lopez, F., Carrasco-Valiente, J., Valero-Rosa, J., Moreno, M. M.,
Sanchez-Sanchez, R., Ortega-Salas, R., Gracia-Navarro, F., Culler, M. D., Ibanez
Costa, A., Gahete, M. D., Requena, M. J., Castano, J. P., Luque, R. M. The
oncogenic role of the spliced somatostatin receptor sst5TMD4 variant in prostate
cancer.
PMID- 28705810
TI - The butyrophilin 3A1 intracellular domain undergoes a conformational change
involving the juxtamembrane region.
AB - Small isoprenoid diphosphates, such as (E)-4-hydroxy-3-methyl-but-2-enyl
diphosphate (HMBPP), are ligands of the internal domain of BTN3A1. Ligand binding
in target cells promotes activation of Vgamma9Vdelta2 T cells. We demonstrate by
small-angle X-ray scattering (SAXS) that HMBPP binding to the internal domain of
BTN3A1 induces a conformational change in the position of the B30.2 domain
relative to the juxtamembrane (JM) region. To better understand the molecular
details of this conformational rearrangement, NMR spectroscopy was used to
discover that the JM region interacts with HMBPP, specifically at the
diphosphate. The spectral location of the affected amide peaks, partial NMR
assignments, and JM mutants (ST296AA or T304A) investigated, confirm that the
backbone amide of at least one Thr (Thr304), adjacent to conserved Ser, comes
close to the HMBPP diphosphate, whereas double mutation of nonconserved residues
(Ser/Thr296/297) may perturb the local fold. Cellular mutation of either of the
identified Thr residues reduces the activation of Vgamma9Vdelta2 T cells by
HMBPP, zoledronate, and POM2-C-HMBP, but not by a partial agonist BTN3 antibody.
Taken together, our results show that ligand binding to BTN3A1 induces a
conformational change within the intracellular domain that involves the JM region
and is required for full activation.-Nguyen, K., Li, J., Puthenveetil, R., Lin,
X., Poe, M. M., Hsiao, C.-H. C., Vinogradova, O., Wiemer, A. J. The butyrophilin
3A1 intracellular domain undergoes a conformational change involving the
juxtamembrane region.
PMID- 28705811
TI - Proprotein convertase Furin1 expression in the Drosophila fat body is essential
for a normal antimicrobial peptide response and bacterial host defense.
AB - Invading pathogens provoke robust innate immune responses in Dipteran insects,
such as Drosophila melanogaster In a systemic bacterial infection, a humoral
response is induced in the fat body. Gram-positive bacteria trigger the Toll
signaling pathway, whereas gram-negative bacterial infections are signaled via
the immune deficiency (IMD) pathway. We show here that the RNA interference
mediated silencing of Furin1-a member of the proprotein convertase enzyme family
specifically in the fat body, results in a reduction in the expression of
antimicrobial peptides. This, in turn, compromises the survival of adult fruit
flies in systemic infections that are caused by both gram-positive and -negative
bacteria. Furin1 plays a nonredundant role in the regulation of immune responses,
as silencing of Furin2, the other member of the enzyme family, had no effect on
survival or the expression of antimicrobial peptides upon a systemic infection.
Furin1 does not directly affect the Toll or IMD signaling pathways, but the
reduced expression of Furin1 up-regulates stress response factors in the fat
body. We also demonstrate that Furin1 is a negative regulator of the Janus
kinase/signal transducer and activator of transcription signaling pathway, which
is implicated in stress responses in the fly. In summary, our data identify
Furin1 as a novel regulator of humoral immunity and cellular stress responses in
Drosophila-Aittomaki, S., Valanne, S., Lehtinen, T., Matikainen, S., Nyman, T.
A., Ramet, M., Pesu, M. Proprotein convertase Furin1 expression in the Drosophila
fat body is essential for a normal antimicrobial peptide response and bacterial
host defense.
PMID- 28705812
TI - Molecular mechanisms underlying metabolic syndrome: the expanding role of the
adipocyte.
AB - The metabolic syndrome (MetS) is defined as a cluster of 3 or more metabolic and
cardiovascular risk factors and represents a serious problem for public health.
Altered function of adipose tissue has a significant impact on whole-body
metabolism and represents a key driver for the development of these metabolic
derangements, collectively referred as to MetS. In particular, increased visceral
and ectopic fat deposition play a major role in the development of insulin
resistance and MetS. A large body of evidence demonstrates that aging and MetS
share several metabolic alterations. Of importance, molecular pathways that
regulate lifespan affect key processes of adipose tissue physiology, and
transgenic mouse models with adipose-specific alterations in these pathways show
derangements of adipose tissue and other metabolic features of MetS, which
highlights a causal link between dysfunctional adipose tissue and deleterious
effects on whole-body homeostasis. This review analyzes adipose tissue-specific
dysfunctions, including metabolic alterations that are related to aging, that
have a significant impact on the development of MetS.-Armani, A., Berry, A.,
Cirulli, F., Caprio, M. Molecular mechanisms underlying metabolic syndrome: the
expanding role of the adipocyte.
PMID- 28705813
TI - A rash localised around the eyes.
PMID- 28705814
TI - Head and Neck MRI Findings in CHARGE Syndrome.
AB - Coloboma of the eye, Heart defects, Atresia of the choanae, Retardation of growth
and/or development, Genital and/or urinary abnormalities, and Ear abnormalities
and deafness (CHARGE) syndrome is a disorder with multiple congenital anomalies
seen on imaging. A retrospective review of 10 patients with CHARGE syndrome who
underwent MR imaging of the brain as part of a preoperative evaluation for
cochlear implantation was conducted. Structural abnormalities of the entire MR
imaging of the head were evaluated, including the auditory system, olfactory
system, face, skull base, and central nervous system. The most frequent MR
imaging findings included dysplasias of the semicircular canals and hypoplasia of
the frontal lobe olfactory sulci. Less frequent findings included cleft
lip/palate and coloboma. Our study uncovered new findings of a J-shaped sella,
dorsal angulation of the clivus, and absent/atrophic parotid glands, not
previously described in patients with CHARGE. Our results emphasize the utility
of MR imaging in the diagnosis and management of patients with CHARGE syndrome.
PMID- 28705815
TI - Sigmoid Sinus Diverticulum, Dehiscence, and Venous Sinus Stenosis: Potential
Causes of Pulsatile Tinnitus in Patients with Idiopathic Intracranial
Hypertension?
AB - BACKGROUND AND PURPOSE: Pulsatile tinnitus is experienced by most patients with
idiopathic intracranial hypertension. The pathophysiology remains uncertain;
however, transverse sinus stenosis and sigmoid sinus diverticulum/dehiscence have
been proposed as potential etiologies. We aimed to determine whether the
prevalence of transverse sinus stenosis and sigmoid sinus diverticulum/dehiscence
was increased in patients with idiopathic intracranial hypertension and pulsatile
tinnitus relative to those without pulsatile tinnitus and a control group.
MATERIALS AND METHODS: CT vascular studies of patients with idiopathic
intracranial hypertension with pulsatile tinnitus (n = 42), without pulsatile
tinnitus (n = 37), and controls (n = 75) were independently reviewed for the
presence of severe transverse sinus stenosis and sigmoid sinus
diverticulum/dehiscence according to published criteria. The prevalence of
transverse sinus stenosis and sigmoid sinus diverticulum/dehiscence in patients
with idiopathic intracranial hypertension with pulsatile tinnitus was compared
with that in the nonpulsatile tinnitus idiopathic intracranial hypertension group
and the control group. Further comparisons included differing degrees of
transverse sinus stenosis (50% and 75%), laterality of transverse sinus
stenosis/sigmoid sinus diverticulum/dehiscence, and ipsilateral transverse sinus
stenosis combined with sigmoid sinus diverticulum/dehiscence. RESULTS: Severe
bilateral transverse sinus stenoses were more frequent in patients with
idiopathic intracranial hypertension than in controls (P < .001), but there was
no significant association between transverse sinus stenosis and pulsatile
tinnitus within the idiopathic intracranial hypertension group. Sigmoid sinus
dehiscence (right- or left-sided) was also more common in patients with
idiopathic intracranial hypertension compared with controls (P = .01), but there
was no significant association with pulsatile tinnitus within the idiopathic
intracranial hypertension group. CONCLUSIONS: While our data corroborate previous
studies demonstrating increased prevalence of sigmoid sinus
diverticulum/dehiscence and transverse sinus stenosis in idiopathic intracranial
hypertension, we did not establish an increased prevalence in patients with
idiopathic intracranial hypertension with pulsatile tinnitus compared with those
without. It is therefore unlikely that these entities represent a direct
structural correlate of pulsatile tinnitus in patients with idiopathic
intracranial hypertension.
PMID- 28705816
TI - Diagnostic Performance of a 10-Minute Gadolinium-Enhanced Brain MRI Protocol
Compared with the Standard Clinical Protocol for Detection of Intracranial
Enhancing Lesions.
AB - BACKGROUND AND PURPOSE: The development of new MR imaging scanners with stronger
gradients and improvement in coil technology, allied with emerging fast imaging
techniques, has allowed a substantial reduction in MR imaging scan times. Our
goal was to develop a 10-minute gadolinium-enhanced brain MR imaging protocol
with accelerated sequences and to evaluate its diagnostic performance compared
with the standard clinical protocol. MATERIALS AND METHODS: Fifty-three patients
referred for brain MR imaging with contrast were scanned with a 3T scanner. Each
MR image consisted of 5 basic fast precontrast sequences plus standard and
accelerated versions of the same postcontrast T1WI sequences. Two
neuroradiologists assessed the image quality and the final diagnosis for each set
of postcontrast sequences and compared their performances. RESULTS: The
acquisition time of the combined accelerated pre- and postcontrast sequences was
10 minutes and 15 seconds; and of the fast postcontrast sequences, 3 minutes and
36 seconds, 46% of the standard sequences. The 10-minute postcontrast axial T1WI
had fewer image artifacts (P < .001) and better overall diagnostic quality (P <
.001). Although the 10-minute MPRAGE sequence showed a tendency to have more
artifacts than the standard sequence (P = .08), the overall diagnostic quality
was similar (P = .66). Moreover, there was no statistically significant
difference in the diagnostic performance between the protocols. The sensitivity,
specificity, and accuracy values for the 10-minute protocol were 100.0%, 88.9%,
and 98.1%. CONCLUSIONS: The 10-minute brain MR imaging protocol with contrast is
comparable in diagnostic performance with the standard protocol in an inpatient
motion-prone population, with the additional benefits of reducing acquisition
times and image artifacts.
PMID- 28705817
TI - Multinodular and Vacuolating Neuronal Tumor of the Cerebrum: A New "Leave Me
Alone" Lesion with a Characteristic Imaging Pattern.
AB - Multinodular and vacuolating neuronal tumor of the cerebrum is a recently
reported benign, mixed glial neuronal lesion that is included in the 2016 updated
World Health Organization classification of brain neoplasms as a unique
cytoarchitectural pattern of gangliocytoma. We report 33 cases of presumed
multinodular and vacuolating neuronal tumor of the cerebrum that exhibit a
remarkably similar pattern of imaging findings consisting of a subcortical
cluster of nodular lesions located on the inner surface of an otherwise normal
appearing cortex, principally within the deep cortical ribbon and superficial
subcortical white matter, which is hyperintense on FLAIR. Only 4 of our cases are
biopsy-proven because most were asymptomatic and incidentally discovered. The
remaining were followed for a minimum of 24 months (mean, 3 years) without
interval change. We demonstrate that these are benign, nonaggressive lesions that
do not require biopsy in asymptomatic patients and behave more like a
malformative process than a true neoplasm.
PMID- 28705818
TI - Intracranial Perishunt Catheter Fluid Collections with Edema, a Sign of Shunt
Malfunction: Correlation of CT/MRI and Nuclear Medicine Findings.
AB - Fluid collections with edema along the intracranial tract of ventriculoperitoneal
shunt catheters in adults are rare and are more frequently seen in children. The
imaging appearance of these fluid collections is frequently confusing and
presents a diagnostic dilemma. We present 6 cases of adult patients noted to have
collections with edema along the tract of ventriculoperitoneal shunt catheters.
To our knowledge, there are no previous studies correlating the CT/MR imaging
findings with nuclear medicine scans in this entity. We hypothesized that when
seen in adults, the imaging findings of a CSF-like fluid collection around the
intracranial ventriculoperitoneal shunt catheter on CT/MR imaging may suggest
areas of CSF accumulation with interstitial edema. It is important to recognize
this rare ventriculoperitoneal shunt complication in adults to prevent
misdiagnosis of an abscess or cystic tumor.
PMID- 28705819
TI - MRI of the Swallow Tail Sign: A Useful Marker in the Diagnosis of Lewy Body
Dementia?
AB - BACKGROUND AND PURPOSE: There are, to date, no MR imaging diagnostic markers for
Lewy body dementia. Nigrosome 1, containing dopaminergic cells, in the substantia
nigra pars compacta is hyperintense on SWI and has been called the swallow tail
sign, disappearing with Parkinson disease. We aimed to study the swallow tail
sign and its clinical applicability in Lewy body dementia and hypothesized that
the sign would be likewise applicable in Lewy body dementia. MATERIALS AND
METHODS: This was a retrospective cross-sectional multicenter study including 97
patients (mean age, 65 +/- 10 years; 46% women), consisting of the following:
controls (n = 21) and those with Lewy body dementia (n = 19), Alzheimer disease
(n = 20), frontotemporal lobe dementia (n = 20), and mild cognitive impairment (n
= 17). All patients underwent brain MR imaging, with susceptibility-weighted
imaging at 1.5T (n = 46) and 3T (n = 51). The swallow tail sign was assessed
independently by 2 neuroradiologists. RESULTS: Interrater agreement was moderate
(kappa = 0.4) between raters. An abnormal swallow tail sign was most common in
Lewy body dementia (63%; 95% CI, 41%-85%; P < .001) and had a predictive value
only in Lewy body dementia with an odds ratio of 9 (95% CI, 3-28; P < .001). The
consensus rating for Lewy body dementia showed a sensitivity of 63%, a
specificity of 79%, a negative predictive value of 89%, and an accuracy of 76%;
values were higher on 3T compared with 1.5T. The usefulness of the swallow tail
sign was rater-dependent with the highest sensitivity equaling 100%. CONCLUSIONS:
The swallow tail sign has diagnostic potential in Lewy body dementia and may be a
complement in the diagnostic work-up of this condition.
PMID- 28705820
TI - Cerebral Microbleeds: A Call for Standardized Advanced Neuroimaging.
PMID- 28705821
TI - Pacemakers in MRI for the Neuroradiologist.
AB - Cardiac implantable electronic devices are frequently encountered in clinical
practice in patients being screened for MR imaging examinations. Traditionally,
the presence of these devices has been considered a contraindication to
undergoing MR imaging. Growing evidence suggests that most of these patients can
safely undergo an MR imaging examination if certain conditions are met. This
document will review the relevant cardiac implantable electronic devices
encountered in practice today, the background physics/technical factors related
to scanning these devices, the multidisciplinary screening protocol used at our
institution for scanning patients with implantable cardiac devices, and our
experience in safely performing these examinations since 2010.
PMID- 28705822
TI - Focal Low and Global High Permeability Predict the Possibility, Risk, and
Location of Hemorrhagic Transformation following Intra-Arterial Thrombolysis
Therapy in Acute Stroke.
AB - BACKGROUND AND PURPOSE: The contrast volume transfer coefficient (Ktrans), which
reflects blood-brain barrier permeability, is influenced by circulation and
measurement conditions. We hypothesized that focal low BBB permeability values
can predict the spatial distribution of hemorrhagic transformation and global
high BBB permeability values can predict the likelihood of hemorrhagic
transformation. MATERIALS AND METHODS: We retrospectively enrolled 106 patients
with hemispheric stroke who received intra-arterial thrombolytic treatment.
Ktrans maps were obtained with first-pass perfusion CT data. The Ktrans values at
the region level, obtained with the Alberta Stroke Program Early CT Score system,
were compared to determine the differences between the hemorrhagic transformation
and nonhemorrhagic transformation regions. The Ktrans values of the whole
ischemic region based on baseline perfusion CT were obtained as a variable to
hemorrhagic transformation possibility at the global level. RESULTS: Forty-eight
(45.3%) patients had hemorrhagic transformation, and 21 (19.8%) had symptomatic
intracranial hemorrhage. At the region level, there were 82 ROIs with hemorrhagic
transformation and parenchymal hemorrhage with a mean Ktrans, 0.5 +/- 0.5/min,
which was significantly lower than that in the nonhemorrhagic transformation
regions (P < .01). The mean Ktrans value of 615 nonhemorrhagic transformation
ROIs was 0.7 +/- 0.6/min. At the global level, there was a significant difference
(P = .01) between the mean Ktrans values of patients with symptomatic
intracranial hemorrhage (1.3 +/- 0.9) and those without symptomatic intracranial
hemorrhage (0.8 +/- 0.4). Only a high Ktrans value at the global level could
predict the occurrence of symptomatic intracranial hemorrhage (P < .01; OR =
5.04; 95% CI, 2.01-12.65). CONCLUSIONS: Global high Ktrans values can predict the
likelihood of hemorrhagic transformation or symptomatic intracranial hemorrhage
at the patient level, whereas focal low Ktrans values can predict the spatial
distributions of hemorrhagic transformation at the region level.
PMID- 28705823
TI - Transient Focal Neurologic Symptoms Correspond to Regional Cerebral Hypoperfusion
by MRI: A Stroke Mimic in Children.
AB - Children who present with acute transient focal neurologic symptoms raise concern
for stroke or transient ischemic attack. We present a series of 16 children who
presented with transient focal neurologic symptoms that raised concern for acute
stroke but who had no evidence of infarction and had unilateral, potentially
reversible imaging features on vascular and perfusion-sensitive brain MR imaging.
Patients were examined with routine brain MR imaging, MRA, perfusion-sensitive
sequences, and DWI. Fourteen (88%) children had lateralized MRA evidence of
arterial tree pruning without occlusion, all had negative DWI findings, and all
showed evidence of hemispheric hypoperfusion by susceptibility-weighted imaging
or arterial spin-labeling perfusion imaging at presentation. These findings
normalized following resolution of symptoms in all children who had follow-up
imaging (6/16, 38%). The use of MR imaging with perfusion-sensitive sequences,
DWI, and MRA can help to rapidly distinguish children with conditions mimicking
stroke from those with acute stroke.
PMID- 28705824
TI - Carotid Plaque Morphology and Ischemic Vascular Brain Disease on MRI.
AB - BACKGROUND AND PURPOSE: Vulnerable carotid plaque components are reported to
increase the risk of cerebrovascular events. Yet, the relation between plaque
composition and subclinical ischemic brain disease is not known. We studied, in
the general population, the association between carotid atherosclerotic plaque
characteristics and ischemic brain disease on MR imaging. MATERIALS AND METHODS:
From the population-based Rotterdam Study, 951 participants underwent both
carotid MR imaging and brain MR imaging. The presence of intraplaque hemorrhage,
lipid core, and calcification and measures of plaque size was assessed in both
carotid arteries. The presence of plaque characteristics in relation to lacunar
and cortical infarcts and white matter lesion volume was investigated and
adjusted for cardiovascular risk factors. Stratified analyses were conducted to
explore effect modification by sex. Additional analyses were conducted per
carotid artery in relation to vascular brain disease in the ipsilateral
hemisphere. RESULTS: Carotid intraplaque hemorrhage was significantly associated
with the presence of cortical infarcts (OR, 1.9; 95% confidence interval, 1.1
3.3). None of the plaque characteristics were related to the presence of lacunar
infarcts. Calcification was the only characteristic that was associated with
higher white matter lesion volume. There was no significant interaction by sex.
CONCLUSIONS: The presence of carotid intraplaque hemorrhage on MR imaging is
independently associated with MR imaging-defined cortical infarcts, but not with
lacunar infarcts. Plaque calcification, but not vulnerable plaque components, is
related to white matter lesion volume.
PMID- 28705825
TI - Reply.
PMID- 28705826
TI - Emergency Department MR Imaging Scanner: Supportive Data.
PMID- 28705827
TI - 3-Hydroxyisobutyrate Dehydrogenase Is Involved in Both, Valine and Isoleucine
Degradation in Arabidopsis thaliana.
AB - In plants, amino acid catabolism is especially relevant in metabolic stress
situations (e.g. limited carbohydrate availability during extended darkness).
Under these conditions, amino acids are used as alternative substrates for
respiration. Complete oxidation of the branched-chain amino acids (BCAAs)
leucine, isoleucine (Ile), and valine (Val) in the mitochondria efficiently
allows the formation of ATP by oxidative phosphorylation. However, the metabolic
pathways for BCAA breakdown are largely unknown so far in plants. A systematic
search for Arabidopsis (Arabidopsis thaliana) genes encoding proteins resembling
enzymes involved in BCAA catabolism in animals, fungi, and bacteria as well as
proteomic analyses of mitochondrial fractions from Arabidopsis allowed the
identification of a putative 3-hydroxyisobutyrate dehydrogenase, AtHDH1
(At4g20930), involved in Val degradation. Systematic substrate screening analyses
revealed that the protein uses 3-hydroxyisobutyrate but additionally 3
hydroxypropionate as substrates. This points to a role of the enzyme not only in
Val but possibly also in Ile metabolism. At4g20930 knockdown plants were
characterized to test this conclusion. Root toxicity assays revealed increased
root growth inhibition of the mutants if cultivated in the presence of Val or Ile
but not in the presence of leucine. We conclude that AtHDH1 has a dual role in
BCAA metabolism in plants.
PMID- 28705828
TI - CRISPR-induced null alleles show that Frost protects Drosophila melanogaster
reproduction after cold exposure.
AB - The ability to survive and reproduce after cold exposure is important in all
kingdoms of life. However, even in a sophisticated genetic model system like
Drosophila melanogaster, few genes have been identified as functioning in cold
tolerance. The accumulation of the Frost (Fst) gene transcript increases after
cold exposure, making it a good candidate for a gene that has a role in cold
tolerance. Despite extensive RNAi knockdown analysis, no role in cold tolerance
has been assigned to Fst CRISPR is an effective technique for completely knocking
down genes, and is less likely to produce off-target effects than GAL4-UAS RNAi
systems. We have used CRISPR-mediated homologous recombination to generate Fst
null alleles, and these Fst alleles uncovered a requirement for FST protein in
maintaining female fecundity following cold exposure. However, FST does not have
a direct role in survival following cold exposure. FST mRNA accumulates in the
Malpighian tubules, and the FST protein is a highly disordered protein with a
putative signal peptide for export from the cell. Future work is needed to
determine whether FST is exported from the Malpighian tubules and directly
interacts with female reproductive tissues post-cold exposure, or whether it is
required for other repair/recovery functions that indirectly alter energy
allocation to reproduction.
PMID- 28705829
TI - Regional variation in undulatory kinematics of two hammerhead species: the
bonnethead (Sphyrna tiburo) and the scalloped hammerhead (Sphyrna lewini).
AB - Hammerhead sharks (Sphyrnidae) exhibit a large amount of morphological variation
within the family, making them the focus of many studies. The size of the
laterally expanded head, or cephalofoil, is inversely correlated with pectoral
fin area. The inverse relationship between cephalofoil and pectoral fin size in
this family suggests that they might serve a complementary role in lift
generation. The cephalofoil is also hypothesized to increase olfaction,
electroreception and vision; however, little is known about how morphological
variation impacts post-cranial swimming kinematics. Previous studies demonstrate
that the bonnethead and scalloped hammerhead have significantly different yaw
amplitude, and we hypothesized that these species utilize varied frequency and
amplitude of undulation along the body. We analyzed video of free-swimming sharks
to examine kinematics and 2D morphological variables of the bonnethead and
scalloped hammerhead. We also examined the second moment of area along the length
of the body and over a size range of animals to determine whether there were
shape differences along the body of these species and whether those changed over
ontogeny. We found that both species swim with the same standardized velocity and
Strouhal number, but there was no correlation between two-dimensional morphology
and swimming kinematics. However, the bonnethead has a dorso-ventrally compressed
anterior trunk and undulates with greater amplitude, whereas the scalloped
hammerhead has a laterally compressed anterior trunk and undulates with lower
amplitude. We propose that differences in cross-sectional trunk morphology
account for interspecific differences in undulatory amplitude. We also found that
for both species, undulatory frequency is significantly greater in the anterior
body compared with all other body regions. We hypothesize that the bonnethead and
scalloped hammerhead swim with a double oscillation system.
PMID- 28705830
TI - Molecular and ultrastructural studies of a fibrillar collagen from octocoral
(Cnidaria).
AB - We report here the biochemical, molecular and ultrastructural features of a
unique organization of fibrillar collagen extracted from the octocoral
Sarcophyton ehrenbergi Collagen, the most abundant protein in the animal kingdom,
is often defined as a structural component of extracellular matrices in
metazoans. In the present study, collagen fibers were extracted from the
mesenteries of S. ehrenbergi polyps. These fibers are organized as filaments and
further compacted as coiled fibers. The fibers are uniquely long, reaching an
unprecedented length of tens of centimeters. The diameter of these fibers is 9+/
0.37 MUm. The amino acid content of these fibers was identified using
chromatography and revealed close similarity in content to mammalian type I and
II collagens. The ultrastructural organization of the fibers was characterized by
means of high-resolution microscopy and X-ray diffraction. The fibers are
composed of fibrils and fibril bundles in the range of 15 to 35 nm. These data
indicate a fibrillar collagen possessing structural aspects of both types I and
II collagen, a highly interesting and newly described form of fibrillar collagen
organization.
PMID- 28705831
TI - Randomised crossover study comparing speed of heart rate display in newborns
using ECG plus pulse oximeter versus pulse oximeter alone.
PMID- 28705833
TI - Erratum. Diabetic Retinopathy: A Position Statement by the American Diabetes
Association. Diabetes Care 2017;40:412-418.
PMID- 28705832
TI - Tricellular junctions: how to build junctions at the TRICkiest points of
epithelial cells.
AB - Tricellular contacts are the places where three cells meet. In vertebrate
epithelial cells, specialized structures called tricellular tight junctions
(tTJs) and tricellular adherens junctions (tAJs) have been identified. tTJs are
important for the maintenance of barrier function, and disruption of tTJ proteins
contributes to familial deafness. tAJs have recently been attracting the
attention of mechanobiologists because these sites are hot spots of epithelial
tension. Although the molecular components, regulation, and function of tTJs and
tAJs, as well as of invertebrate tricellular junctions, are beginning to be
characterized, many questions remain. Here we broadly cover what is known about
tricellular junctions, propose a new model for tension transmission at tAJs, and
discuss key open questions.
PMID- 28705834
TI - Visit-to-Visit Variations in Fasting Plasma Glucose and HbA1c Associated With an
Increased Risk of Alzheimer Disease: Taiwan Diabetes Study.
AB - OBJECTIVE: The relationship between glycemic variability and the incidence of
Alzheimer disease (AD) in patients with type 2 diabetes mellitus (T2DM) is
unclear. The aim of this study was to examine visit-to-visit variations in
fasting plasma glucose (FPG) and glycated hemoglobin (HbA1c) represented by the
coefficient of variation (CV) and to determine whether they were independently
associated with AD, irrespective of HbA1c and other traditional risk factors in
such patients. RESEARCH DESIGN AND METHODS: Patients with T2DM enrolled in the
National Diabetes Care Management Program, age >=60 years, and without diagnosis
of AD (n = 16,706) were included in the study. Potential risk factors were
analyzed using extended Cox proportional hazards regression models for competing
risk of mortality on AD incidence. RESULTS: During a median follow-up of 8.88
years, 831 incident cases of AD were identified, with a crude incidence rate of
3.5/1,000 person-years. After adjustment for sociodemographic factors, lifestyle
behaviors, diabetes-related variables, FPG and HbA1c, drug-related variables, and
comorbidities, both FPG CV and HbA1c CV were found to be significant predictors
of AD, with corresponding hazard ratios of 1.27 (95% CI 1.06-1.52) for the third
tertile in FPG CV and 1.32 (95% CI 1.11-1.58) for the third tertile in HbA1c CV.
CONCLUSIONS: FPG CV and HbA1c CV are independently associated with AD. The
associations between glycemic variability and AD demonstrated in this study
suggest a linked pathophysiological mechanism, which is worthy of further
investigation. Further research is required to confirm our results and to
evaluate whether FPG CV and HbA1c CV can be valuable therapeutic targets for
patients with T2DM at risk.
PMID- 28705835
TI - Transendothelial movement of adiponectin is restricted by glucocorticoids.
AB - Altered permeability of the endothelial barrier in a variety of tissues has
implications both in disease pathogenesis and treatment. Glucocorticoids are
potent mediators of endothelial permeability, and this forms the basis for their
heavily prescribed use as medications to treat ocular disease. However, the
effect of glucocorticoids on endothelial barriers elsewhere in the body is less
well studied. Here, we investigated glucocorticoid-mediated changes in
endothelial flux of Adiponectin (Ad), a hormone with a critical role in diabetes.
First, we used monolayers of endothelial cells in vitro and found that the
glucocorticoid dexamethasone increased transendothelial electrical resistance and
reduced permeability of polyethylene glycol (PEG, molecular weight 4000 Da).
Dexamethasone reduced flux of Ad from the apical to basolateral side, measured
both by ELISA and Western blotting. We then examined a diabetic rat model induced
by treatment with exogenous corticosterone, which was characterized by glucose
intolerance and hyperinsulinemia. There was no change in circulating Ad but less
Ad protein in skeletal muscle homogenates, despite slightly higher mRNA levels,
in diabetic vs control muscles. Dexamethasone-induced changes in Ad flux across
endothelial monolayers were associated with alterations in the abundance of
select claudin tight junction (TJ) proteins. shRNA-mediated knockdown of one such
gene, claudin-7, in HUVEC resulted in decreased TEER and increased adiponectin
flux, confirming the functional significance of Dex-induced changes in its
expression. In conclusion, our study identifies glucocorticoid-mediated
reductions in flux of Ad across endothelial monolayers in vivo and in vitro This
suggests that impaired Ad action in target tissues, as a consequence of reduced
transendothelial flux, may contribute to the glucocorticoid-induced diabetic
phenotype.
PMID- 28705836
TI - Essential and selective role of SNX12 in transport of endocytic and retrograde
cargo.
AB - The endosomal protein-sorting machineries play vital roles in diverse
physiologically important cellular processes. Much of the core membrane-sorting
apparatus is conserved in evolution, such as retromer, which is involved in the
recycling of a diverse set of cargoes via the retrograde trafficking route. Here,
in an RNAi-based loss-of-function study, we identified that suppression of SNX12
leads to a severe blockage in CIM6PR (also known as IGF2R) transport and alters
the morphology of the endocytic compartments. We demonstrate that SNX12 is
involved in the early phase of CIM6PR transport, and mediates receptor recycling
upstream of the other well-established SNX components of retromer. Ultra
structural analysis revealed that SNX12 resides on tubulo-vesicular structures,
despite it lacking a BAR domain. Furthermore, we illustrate that SNX12 plays a
key role in intraluminal vesicle formation and in the maturation of a
subpopulation of early endosomes into late endosomes, thereby regulating
selective endocytic transport of cargo for degradation. This study therefore
provides evidence for the existence of early endosomal subpopulations that have
differential roles in the sorting of the cargoes along endocytic degradative
pathways.
PMID- 28705837
TI - The B-type cyclin CYB-1 maintains the proper position and number of centrosomes
during spermatogenesis in Caenorhabditis elegans.
AB - Depletion of cyb-1, a major B-type cyclin expressed during Caenorhabditis elegans
spermatogenesis, causes a meiotic division arrest in diakinesis-stage
spermatocytes with multiple and mispositioned centrosomes. Association of the two
nuclear membrane proteins SUN-1 and ZYG-12 is essential for centrosome-nuclear
envelope attachment. We found that depletion of sun-1 causes centrosome defects
similar to those caused by cyb-1 depletion in diakinesis-stage spermatocytes. In
addition, Ser8 and Ser43 residues in SUN-1 are dephosphorylated in cyb-1-depleted
diakinesis-stage spermatocytes. Nevertheless, dephosphorylation of these residues
was not sufficient to reproduce the cyb-1-related centrosome defects. We then
found that the ZYG-12::GFP signal in the nuclear envelope was significantly
reduced in the cyb-1-depleted diakinesis-stage spermatocytes. However, only
mispositioned but not multiplied centrosomes were observed in zyg-12 mutant
diakinesis-stage spermatocytes, suggesting that zyg-12 is not involved in the
centrosome duplication at this stage. Our results suggest that CYB-1 functions to
maintain proper positioning of centrosomes during spermatogenesis by regulating
phosphorylation of SUN-1, which is possibly crucial for the association between
SUN-1 and ZYG-12. This phosphorylation of SUN-1 may also regulate centrosome
duplication independently of ZYG-12.
PMID- 28705838
TI - Leukofiltration plus pathogen reduction prevents alloimmune platelet
refractoriness in a dog transfusion model.
AB - Human lymphocyte antigen alloimmunization to filter leukoreduced (F-LR) platelets
occurs in about 18% of immunosuppressed thrombocytopenic hematology/oncology
patients and represents a significant challenge for effective chemotherapy. In a
dog platelet transfusion model, we have evaluated other methods of preventing
alloimmune platelet refractoriness and demonstrated that successful methods in
our dog model are transferable to man. In the present study, donor/recipient
pairs were dog lymphocyte antigen DR-B incompatible (88% of the pairs), and
recipient dogs received up to 8 weekly treated transfusions from a single donor
(a highly immunogenic stimulus), or until platelet refractoriness. Continued
acceptance of F-LR platelets occurred in 6 of 13 recipients (46%), but neither
gamma-irradiation (gamma-I; 0 of 5) nor Mirasol pathogen reduction (MPR; 1 of 7)
treatment of donor platelets prevented alloimmune platelet refractoriness.
Combining gamma-I with F-LR was associated with only 2 of 10 (20%) recipients
accepting the transfused platelets. Surprisingly, F-LR platelets that then
underwent MPR were accepted by 21 of 22 (95%) recipients (P < .001 vs F-LR +
gamma-I recipients). Furthermore, 7 of 21 (33%) of these accepting recipients
demonstrated specific tolerance to 8 more weekly donor transfusions that had not
been treated. In addition, platelet concentrates prepared from F-LR + MPR whole
blood were also nonimmunogenic; that is, 10 of 10 (100%) recipients accepted
donor platelets. Overall, 31 of 32 (97%) recipients accepted F-LR + MPR
platelets; none developed antibodies to donor lymphocytes. These data are the
highest rate of acceptance for platelet transfusions reported in either animals
or man. This approach to platelet transfusion may be particularly important when
supporting patients with intact immune systems, such as in myelodysplastic
syndromes.
PMID- 28705839
TI - Circulating dsDNA, endothelial injury, and complement activation in thrombotic
microangiopathy and GVHD.
AB - Transplant-associated thrombotic microangiopathy (TA-TMA) is a common and poorly
recognized complication of hematopoietic stem cell transplantation (HSCT)
associated with excessive complement activation, likely triggered by endothelial
injury. An important missing piece is the link between endothelial injury and
complement activation. We hypothesized that neutrophil extracellular traps (NETs)
mechanistically link endothelial damage with complement activation and subsequent
TA-TMA. Neutrophil activation releases granule proteins together with double
stranded DNA (dsDNA) to form extracellular fibers known as NETs. NETs have been
shown to activate complement and can be assessed in humans by quantification of
dsDNA in serum. We measured levels of dsDNA, as a surrogate for NETs in 103
consecutive pediatric allogeneic transplant recipients at day 0, +14, +30, +60,
and +100. A spike in dsDNA production around day +14 during engraftment was
associated with subsequent TA-TMA development. Peak dsDNA production around day
+14 was associated with interleukin-8-driven neutrophil recovery. Increased dsDNA
levels at days +30, +60, and +100 were also associated with increased mortality
and gastrointestinal graft-versus-host disease (GVHD). NETs may serve as a
mechanistic link between endothelial injury and complement activation. NET
formation may be one mechanism contributing to the clinical overlap between GVHD
and TA-TMA.
PMID- 28705840
TI - Central retinal artery occlusion in a 30-year-old woman taking tranexamic acid.
AB - We present a case of a 30-year-old woman who suffered a central retinal artery
occlusion while taking tranexamic acid. She had no vascular risk factors and was
placed on the drug for treatment of menorrhagia. After 1 month of taking the
drug, she suffered a central retinal artery occlusion in her left eye. Tranexamic
acid was discontinued to prevent vision loss in the following eye. She remains
with no perception of light vision in the affected eye.
PMID- 28705841
TI - Primary cardiac leiomyosarcoma presenting as haemoptysis in a 22-year-old
patient: an unusual presentation of a rare condition.
AB - Primary cardiac sarcomas are rare malignant tumours and among them,
leiomyosarcoma is extremely rare. They are especially rare in a young age group.
We present a case of a 22-year-old male patient with primary leiomyosarcoma of
the left atrium involving the pulmonary veins who presented with haemoptysis and
shortness of breath. He underwent surgical excision of the tumour along with
mitral valve replacement followed by adjuvant chemotherapy. No recurrence was
reported on his second 6 monthly follow-ups.
PMID- 28705842
TI - Facial palsy and atrial fibrillation: a special case of Ramsay Hunt syndrome.
AB - Ramsay Hunt syndrome (herpes zoster oticus) is a rare complication of latent
Varicella Zoster virus infection. It can be complicated by permanent hearing
loss, loss of taste and postherpetic neuralgia. Although Ramsay Hunt syndrome
most prominently involves the facial nerve, a number of other cranial nerves can
be involved such as the vestibulocochlear, glossopharyngeal and the vagus nerve.
We report on a case of Ramsay Hunt syndrome with cranial polyneuritis complicated
by atrial fibrillation. Vagal involvement as evidenced by physical examination
and MRI findings was present in our patient. We hypothesise that viral vagal
neuritis likely contributed to the development of atrial fibrillation in our
patient through involvement of the autonomic components of the vagus nerve.
PMID- 28705843
TI - Headache, TIA and subarachnoid haemorrhage: dissecting an unusual cause for
stroke-like symptoms.
AB - We present a case of supraclinoid internal carotid artery dissection. Eleven
months prior, the patient developed isolated periorbital pain and was diagnosed
with giant-cell arteritis with iritis. The patient experienced recurrent spells
concerning for transient ischaemic attacks and was transferred to our institution
for endovascular intervention after head CT revealed an embolic infarct with a
'dense middle cerebral artery sign.' Digital subtraction angiography was negative
for occlusion, instead demonstrating luminal stenosis and poststenotic
dilatation. He subsequently experienced acute neurological decline secondary to
massive subarachnoid haemorrhage. Non-invasive vascular imaging revealed an
intimal flap and a pseudoaneurysm at the site of luminal stenosis, confirming our
suspicion for intracranial carotid artery dissection. Given the moribund clinical
state, the family opted to withdraw care, and he quickly expired.
PMID- 28705844
TI - Ventricular fibrillation induced by high-output ICD shock: report of cases and
review of literature.
AB - This report highlights the importance of realising that even the modern-day
implantable cardioverter defibrillators (ICDs) with R wave synchronised
appropriate shocks have a potential proarrhythmic effect. We present two cases of
ventricular fibrillation induction resulting from an appropriate ICD shock
observed in two different patients at our institution. Such cases have not been
reported before. We discuss the possible reasons for our observations and are
also submitting a pertinent literature review with our reports.
PMID- 28705845
TI - Urodynamic findings in Susac syndrome: first reported filling cystometrogram.
AB - Susac syndrome is a rare neurological disease, with only 300 cases reported in
the literature. Lower urinary symptoms are not an uncommon feature of the
disease, yet there is no information on specific dysfunction typical urodynamic
findings associated with the disease. We present what we believe to be the first
reported filling cystometrogram study of Susac syndrome for the evaluation of
voiding dysfunction.
PMID- 28705846
TI - A novel case of Raoultella planticola osteomyelitis and epidural abscess.
AB - A spinal epidural abscess is the collection of pus in the epidural space, and is
a potentially life-threatening condition that requires early detection and prompt
management. Almost two-thirds of cases are caused by Staphylococcus aureus,
followed by Gram-negative bacilli which account for approximately 16% of cases.
Raoultella planticola is an emerging pathogen, and is an extremely rare cause of
invasive infection in humans. It has been reported to cause urinary tract
infections, pneumonia, bacteraemia, cholangitis, cholecystitis, conjunctivitis
and soft tissue infections. We report the first case, to our knowledge, of R.
planticola osteomyelitis and spinal epidural abscess.
PMID- 28705847
TI - A rare case of Hodgkin's lymphoma presenting with papulonecrotic tuberculid.
PMID- 28705848
TI - Malar rash with pulmonary hypertension and chronic obstructive pulmonary disease.
PMID- 28705849
TI - Anaplastic carcinoma of thyroid gland with widespread soft tissue metastasis: an
unusual presentation.
AB - Anaplastic thyroid cancer is the rarest tumour of the thyroid gland, representing
only 2% of clinically recognised thyroid cancers. The most common metastatic
sites are lungs, followed by the intrathoracic and neck lymph nodes. We report
the case of a 62-year-old woman who presented to our setting with multiple soft
tissue nodules, thyroid mass, head swelling and weight loss. Radiological
investigation showed a large thyroid mass with widespread metastasis in
subcutaneous tissues of both upper limbs, chest and abdomen. Metastasis was also
found in lungs, skull and adrenal glands after which the patient was diagnosed
with stage IVc anaplastic thyroid carcinoma (ATC). After careful consideration of
patient's clinical condition with multiple poor prognostic factors, medical
therapy was withheld and she was discharged on hospice care. The patient expired
after 1 month. In ATC, metastasis to subcutaneous tissue is an extremely rare
occurrence of which there is hardly any evidence in literature.
PMID- 28705850
TI - Fatal case of descending necrotising mediastinitis.
PMID- 28705851
TI - An unconventional valvuloplasty: severe pulmonary stenosis with 'candy cane'
inferior vena cava.
AB - Femoral vein is the usual approach to balloon pulmonary valvuloplasty (BPV).
However, alternative access may be mandated in some peculiar situations. We
hereby report a 10-year-old patient with symptomatic severe valvular pulmonary
stenosis with interrupted inferior vena cava which was successfully treated with
transjugular BPV. Technical considerations for this approach as well as other
possible options for such patients are discussed.
PMID- 28705852
TI - The challenge of hospital-related thrombosis.
PMID- 28705853
TI - A molecular roadmap for midostaurin in mastocytosis.
PMID- 28705854
TI - Targeting deubiquitinases in CLL.
PMID- 28705855
TI - Soluble P-selectin is the smoke, not the fire.
PMID- 28705856
TI - Factor V marks platelet-primed megakaryocytes.
PMID- 28705857
TI - Myocardial fibrosis: the heart of diastole?
PMID- 28705858
TI - Bruised platelet transfusions work.
PMID- 28705859
TI - Checking up on checkpoint inhibitors.
PMID- 28705860
TI - CART attack.
PMID- 28705861
TI - Myeloid leukemia associated with Down syndrome.
PMID- 28705862
TI - Diagnosing therapy-related acute myeloid leukemia with 8% blasts in bone marrow
with concomitant plasma cell myeloma.
PMID- 28705863
TI - Fischer K, Al-Sawaf O, Fink A-M, et al. Venetoclax and obinutuzumab in chronic
lymphocytic leukemia. Blood. 2017;129(19):2702-2705.
PMID- 28705864
TI - Cannavo A, Valsecchi C, Garagiola I, et al. Nonneutralizing antibodies against
factor VIII and risk of inhibitor development in severe hemophilia A. Blood.
2017;129(10):1245-1250.
PMID- 28705865
TI - With Great Power Comes Great Responsibility: Big Data Research From the National
Inpatient Sample.
PMID- 28705866
TI - Better-Not Just Bigger-Data Analytics.
PMID- 28705867
TI - Finding value in 'inappropriate' visits: A new study demonstrates how variation
in ED use for preventable visits can be used to detect problems with access to
healthcare in our communities.
PMID- 28705868
TI - Authors' response: overcautious adoption of extracorporeal cardiopulmonary
resuscitation.
PMID- 28705869
TI - Auditory cortex interneuron development requires cadherins operating hair-cell
mechanoelectrical transduction.
AB - Many genetic forms of congenital deafness affect the sound reception antenna of
cochlear sensory cells, the hair bundle. The resulting sensory deprivation
jeopardizes auditory cortex (AC) maturation. Early prosthetic intervention should
revive this process. Nevertheless, this view assumes that no intrinsic AC
deficits coexist with the cochlear ones, a possibility as yet unexplored. We show
here that many GABAergic interneurons, from their generation in the medial
ganglionic eminence up to their settlement in the AC, express two cadherin
related (cdhr) proteins, cdhr23 and cdhr15, that form the hair bundle tip links
gating the mechanoelectrical transduction channels. Mutant mice lacking either
protein showed a major decrease in the number of parvalbumin interneurons
specifically in the AC, and displayed audiogenic reflex seizures. Cdhr15- and
Cdhr23-expressing interneuron precursors in Cdhr23-/- and Cdhr15-/- mouse
embryos, respectively, failed to enter the embryonic cortex and were scattered
throughout the subpallium, consistent with the cell polarity abnormalities we
observed in vitro. In the absence of adhesion G protein-coupled receptor V1
(adgrv1), another hair bundle link protein, the entry of Cdhr23- and Cdhr15
expressing interneuron precursors into the embryonic cortex was also impaired.
Our results demonstrate that a population of newborn interneurons is endowed with
specific cdhr proteins necessary for these cells to reach the developing AC. We
suggest that an "early adhesion code" targets populations of interneuron
precursors to restricted neocortical regions belonging to the same functional
area. These findings open up new perspectives for auditory rehabilitation and
cortical therapies in patients.
PMID- 28705870
TI - On the promotion of human flourishing.
AB - Many empirical studies throughout the social and biomedical sciences focus only
on very narrow outcomes such as income, or a single specific disease state, or a
measure of positive affect. Human well-being or flourishing, however, consists in
a much broader range of states and outcomes, certainly including mental and
physical health, but also encompassing happiness and life satisfaction, meaning
and purpose, character and virtue, and close social relationships. The empirical
literature from longitudinal, experimental, and quasiexperimental studies is
reviewed in attempt to identify major determinants of human flourishing, broadly
conceived. Measures of human flourishing are proposed. Discussion is given to the
implications of a broader conception of human flourishing, and of the research
reviewed, for policy, and for future research in the biomedical and social
sciences.
PMID- 28705871
TI - Reply to Csifcsak and Mittner: Fitting data to neural models of mind-wandering.
PMID- 28705872
TI - Linking brain networks and behavioral variability to different types of mind
wandering.
PMID- 28705873
TI - Correction.
PMID- 28705874
TI - Automated Quantification of Low-Amplitude Abnormal QRS Peaks From High-Resolution
ECG Recordings Predicts Arrhythmic Events in Patients With Cardiomyopathy.
AB - BACKGROUND: Cardiomyopathy patients are at risk of sudden death, typically from
scar-related abnormalities of electrical activation that promote ventricular
tachyarrhythmias. Abnormal intra-QRS peaks may provide a measure of altered
activation. We hypothesized that quantification of such QRS peaks (QRSp) in high
resolution ECGs would predict arrhythmic events in implantable cardioverter
defibrillator (ICD)-eligible cardiomyopathy patients. METHODS AND RESULTS: Ninety
nine patients with ischemic or non-ischemic dilated cardiomyopathy undergoing
prophylactic ICD implantation were prospectively enrolled (age 62+/-11 years,
left ventricular ejection fraction 27+/-7%). High-resolution (1024 Hz) digital 12
lead ECGs were recorded during intrinsic rhythm. QRSp was quantified for each
precordial lead as the total number of low-amplitude deflections that deviated
from their respective naive QRS template. The primary end point of arrhythmic
events was defined as appropriate ICD therapy or sustained ventricular
tachyarrhythmias. After a median follow-up of 24 (15-43) months, 20 (20%)
patients had arrhythmic events. Both QRSp and QRS duration were greater in those
with arrhythmic events (both P<0.001) and this was consistent for QRSp for both
cardiomyopathy types. In a multivariable Cox regression model that included age,
left ventricular ejection fraction, QRS duration, and QRSp, only QRSp was an
independent predictor of arrhythmic events (hazard ratio, 2.1; P<0.001). Receiver
operating characteristic analysis revealed that a QRSp >=2.25 identified
arrhythmic events with greater sensitivity (100% versus 70%, P<0.05) and negative
predictive value (100% versus 89%, P<0.05) than QRS duration >=120 ms.
CONCLUSIONS: QRSp measured from high-resolution digital 12-lead ECGs
independently predicts ventricular tachyarrhythmias in ICD-eligible
cardiomyopathy patients. This novel QRS morphology index has the potential to
improve sudden death risk stratification and patient selection for prophylactic
ICD therapy.
PMID- 28705876
TI - Demonstration of Persistent Conduction Across the Mitral Isthmus via the Vein of
Marshall With High-Density Activation Mapping.
PMID- 28705875
TI - Electrical and Structural Substrate of Arrhythmogenic Right Ventricular
Cardiomyopathy Determined Using Noninvasive Electrocardiographic Imaging and Late
Gadolinium Magnetic Resonance Imaging.
AB - BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a
significant cause of sudden cardiac death in the young. Improved noninvasive
assessment of ARVC and better understanding of the disease substrate are
important for improving patient outcomes. METHODS AND RESULTS: We studied 20
genotyped ARVC patients with a broad spectrum of disease using
electrocardiographic imaging (a method for noninvasive cardiac electrophysiology
mapping) and advanced late gadolinium enhancement cardiac magnetic resonance scar
imaging. Compared with 20 healthy controls, ARVC patients had longer ventricular
activation duration (median, 52 versus 42 ms; P=0.007) and prolonged mean
epicardial activation-recovery intervals (a surrogate for local action potential
duration; median, 275 versus 241 ms; P=0.014). In these patients, we observed
abnormal and varied epicardial activation breakthrough locations and regions of
nonuniform conduction and fractionated electrograms. Nonuniform conduction and
fractionated electrograms were present in the early concealed phase of ARVC.
Electrophysiological abnormalities colocalized with late gadolinium enhancement
scar, indicating a relationship with structural disease. Premature ventricular
contractions were common in ARVC patients with variable initiation sites in both
ventricles. Premature ventricular contraction rate increased with exercise, and
within anatomic segments, it correlated with prolonged repolarization, electric
markers of scar, and late gadolinium enhancement (all P<0.001). CONCLUSIONS:
Electrocardiographic imaging reveals electrophysiological substrate properties
that differ in ARVC patients compared with healthy controls. A novel mechanistic
finding is the presence of repolarization abnormalities in regions where
ventricular ectopy originates. The results suggest a potential role for
electrocardiographic imaging and late gadolinium enhancement in early diagnosis
and noninvasive follow-up of ARVC patients.
PMID- 28705877
TI - Letter by Pachon-Mateos and Pachon-Mateos Regarding Article, "Targets and End
Points in Cardiac Autonomic Denervation Procedures" and Editorial, "Selective
Modulation of the Cardiac Autonomic Nervous System: A New Strategy for Treatment
of Cardioinhibitory Syncope".
PMID- 28705878
TI - Response by Rivarola and Scanavacca to Letter Regarding Article, "Targets and End
Points in Cardiac Autonomic Denervation Procedures".
PMID- 28705879
TI - Response by Mulpuru and Shen to Letter Regarding Article, "Selective Modulation
of the Cardiac Autonomic Nervous System: A New Strategy for Treatment of
Cardioinhibitory Syncope".
PMID- 28705880
TI - Mapping the Electrical Substrate in Arrhythmogenic Right Ventricular
Cardiomyopathy: There Is More Than Meets the Eye.
PMID- 28705882
TI - New law will force hospitals to charge foreign patients for non-urgent care.
PMID- 28705881
TI - Defining a Novel Role for the Pdx1 Transcription Factor in Islet beta-Cell
Maturation and Proliferation During Weaning.
AB - The transcription factor encoded by the Pdx1 gene is a critical transcriptional
regulator, as it has fundamental actions in the formation of all pancreatic cell
types, islet beta-cell development, and adult islet beta-cell function.
Transgenic- and cell line-based experiments have identified 5'-flanking conserved
sequences that control pancreatic and beta-cell type-specific transcription,
which are found within areas I (bp -2694 to -2561), II (bp -2139 to -1958), III
(bp -1879 to -1799), and IV (bp -6200 to -5670). Because of the presence in area
IV of binding sites for transcription factors associated with pancreas
development and islet cell function, we analyzed how an endogenous deletion
mutant affected Pdx1 expression embryonically and postnatally. The most striking
result was observed in male Pdx1DeltaIV mutant mice after 3 weeks of birth (i.e.,
the onset of weaning), with only a small effect on pancreas organogenesis and no
deficiencies in their female counterparts. Compromised Pdx1 mRNA and protein
levels in weaned male mutant beta-cells were tightly linked with hyperglycemia,
decreased beta-cell proliferation, reduced beta-cell area, and altered expression
of Pdx1-bound genes that are important in beta-cell replication, endoplasmic
reticulum function, and mitochondrial activity. We discuss the impact of these
novel findings to Pdx1 gene regulation and islet beta-cell maturation
postnatally.
PMID- 28705883
TI - Assessing genome-wide copy number variation in the Han Chinese population.
AB - BACKGROUND: Copy number variation (CNV) is a valuable source of genetic diversity
in the human genome and a well-recognised cause of various genetic diseases.
However, CNVs have been considerably under-represented in population-based
studies, particularly the Han Chinese which is the largest ethnic group in the
world. OBJECTIVES: To build a representative CNV map for the Han Chinese
population. METHODS: We conducted a genome-wide CNV study involving 451 male Han
Chinese samples from 11 geographical regions encompassing 28 dialect groups,
representing a less-biased panel compared with the currently available data. We
detected CNVs by using 4.2M NimbleGen comparative genomic hybridisation array and
whole-genome deep sequencing of 51 samples to optimise the filtering conditions
in CNV discovery. RESULTS: A comprehensive Han Chinese CNV map was built based on
a set of high-quality variants (positive predictive value >0.8, with sizes
ranging from 369 bp to 4.16 Mb and a median of 5907 bp). The map consists of 4012
CNV regions (CNVRs), and more than half are novel to the 30 East Asian CNV
Project and the 1000 Genomes Project Phase 3. We further identified 81 CNVRs
specific to regional groups, which was indicative of the subpopulation structure
within the Han Chinese population. CONCLUSIONS: Our data are complementary to
public data sources, and the CNV map may facilitate in the identification of
pathogenic CNVs and further biomedical research studies involving the Han Chinese
population.
PMID- 28705884
TI - Quantitative analysis of protein interaction network dynamics in yeast.
AB - Many cellular functions are mediated by protein-protein interaction networks,
which are environment dependent. However, systematic measurement of interactions
in diverse environments is required to better understand the relative importance
of different mechanisms underlying network dynamics. To investigate environment
dependent protein complex dynamics, we used a DNA-barcode-based multiplexed
protein interaction assay in Saccharomyces cerevisiae to measure in vivo
abundance of 1,379 binary protein complexes under 14 environments. Many binary
complexes (55%) were environment dependent, especially those involving
transmembrane transporters. We observed many concerted changes around highly
connected proteins, and overall network dynamics suggested that "concerted"
protein-centered changes are prevalent. Under a diauxic shift in carbon source
from glucose to ethanol, a mass-action-based model using relative mRNA levels
explained an estimated 47% of the observed variance in binary complex abundance
and predicted the direction of concerted binary complex changes with 88%
accuracy. Thus, we provide a resource of yeast protein interaction measurements
across diverse environments and illustrate the value of this resource in
revealing mechanisms of network dynamics.
PMID- 28705885
TI - Fibroblast Growth Factor 23 and Kidney Disease Progression in Autosomal Dominant
Polycystic Kidney Disease.
AB - BACKGROUND AND OBJECTIVES: Increases in fibroblast growth factor 23 precede
kidney function decline in autosomal dominant polycystic kidney disease; however,
the role of fibroblast growth factor 23 in autosomal dominant polycystic kidney
disease has not been well characterized. DESIGN, SETTING, PARTICIPANTS &
MEASUREMENTS: We measured intact fibroblast growth factor 23 levels in baseline
serum samples from 1002 participants in the HALT-PKD Study A (n=540; mean eGFR
=91+/-17 ml/min per 1.73 m2) and B (n=462; mean eGFR =48+/-12 ml/min per 1.73
m2). We used linear mixed and Cox proportional hazards models to test
associations between fibroblast growth factor 23 and eGFR decline, percentage
change in height-adjusted total kidney volume, and composite of time to 50%
reduction in eGFR, onset of ESRD, or death. RESULTS: Median (interquartile range)
intact fibroblast growth factor 23 was 44 (33-56) pg/ml in HALT-PKD Study A and
69 (50-93) pg/ml in Study B. In adjusted models, annualized eGFR decline was
significantly faster in the upper fibroblast growth factor 23 quartile (Study A:
quartile 4, -3.62; 95% confidence interval, -4.12 to -3.12 versus quartile 1,
2.51; 95% confidence interval, -2.71 to -2.30 ml/min per 1.73 m2; P for trend
<0.001; Study B: quartile 4, -3.74; 95% confidence interval, -4.14 to -3.34
versus quartile 1, -2.78; 95% confidence interval, -2.92 to -2.63 ml/min per 1.73
m2; P for trend <0.001). In Study A, higher fibroblast growth factor 23 quartiles
were associated with greater longitudinal percentage increase in height-adjusted
total kidney volume in adjusted models (quartile 4, 6.76; 95% confidence
interval, 5.57 to 7.96 versus quartile 1, 6.04; 95% confidence interval, 5.55 to
6.54; P for trend =0.03). In Study B, compared with the lowest quartile, the
highest fibroblast growth factor 23 quartile was associated with elevated risk
for the composite outcome (hazard ratio, 3.11; 95% confidence interval, 1.84 to
5.25). Addition of fibroblast growth factor 23 to a model of annualized decline
in eGFR>=3.0 ml/min per 1.73 m2 did not improve risk prediction. CONCLUSIONS:
Higher serum fibroblast growth factor 23 concentration was associated with kidney
function decline, height-adjusted total kidney volume percentage increase, and
death in patients with autosomal dominant polycystic kidney disease. However,
fibroblast growth factor 23 did not substantially improve prediction of rapid
kidney function decline.
PMID- 28705886
TI - Thyroid Status, Quality of Life, and Mental Health in Patients on Hemodialysis.
AB - BACKGROUND AND OBJECTIVES: In the general population, there is increasing
recognition of the effect of thyroid function on patient-centered outcomes,
including health-related quality of life and depression. Although hypothyroidism
is highly prevalent in hemodialysis patients, it is unknown whether thyroid
status is a risk factor for impaired health-related quality of life or mental
health in this population. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We
examined the association of thyroid status, defined by serum thyrotropin, with
health-related quality of life and depressive symptoms over time in a prospective
cohort of 450 patients on hemodialysis from 17 outpatient dialysis facilities
from May of 2013 to May of 2015 who underwent protocolized thyrotropin testing,
Short-Form 36 surveys, and Beck Depression Inventory-II questionnaires every 6
months. We examined the association of baseline and time-dependent thyrotropin
categorized as tertiles and continuous variables with eight Short-Form 36 domains
and Beck Depression Inventory-II scores using expanded case mix plus laboratory
adjusted linear mixed effects models. RESULTS: In categorical analyses, the
highest baseline thyrotropin tertile was associated with a five-point lower Short
Form 36 domain score for energy/fatigue (P=0.04); the highest time-dependent
tertile was associated with a five-point lower physical function score (P=0.03;
reference: lowest tertile). In continuous analyses, higher baseline serum
thyrotropin levels (+Delta1 mIU/L) were associated with lower role limitations
due to physical health (beta=-1.3; P=0.04), energy/fatigue (beta=-0.8; P=0.03),
and pain scores (beta=-1.4; P=0.002), equivalent to five-, three-, and five-point
lower scores, respectively, for every 1-SD higher thyrotropin. Higher time
dependent thyrotropin levels were associated with lower role limitations due to
physical health scores (beta=-1.0; P=0.03), equivalent to a three-point decline
for every 1-SD higher thyrotropin. Baseline and time-dependent thyrotropin were
not associated with Beck Depression Inventory-II scores. CONCLUSIONS: In patients
on hemodialysis, higher serum thyrotropin levels are associated with impaired
health-related quality of life across energy/fatigue, physical function, and pain
domains. Studies are needed to determine if thyroid-modulating therapy improves
the health-related quality of life of hemodialysis patients with thyroid
dysfunction.
PMID- 28705889
TI - An innovative approach to collaborative simulation training on teamwork skills
for pediatric residents and nursing students.
PMID- 28705890
TI - Mechanical thrombectomy of M1 and M2 middle cerebral artery occlusions.
AB - BACKGROUND: Over half of patients who receive intravenous tissue plasminogen
activator for middle cerebral artery division (MCA-M2) occlusion do not
recanalize, leaving a large percentage of patients who may need mechanical
thrombectomy (MT). However, the outcomes of MT for M2 occlusion have not been
well characterized. OBJECTIVE: To determine if MT of M2 occlusion is as safe and
efficacious as current standard-of-care MT for M1 occlusions. METHODS: With
institutional review board approval, we retrospectively reviewed records of 212
patients undergoing MT for isolated MCA M1 or M2 occlusions during a 36-month
period (Sept 2013 to Sept 2016) at two centres. Treatment variables, clinical
outcomes, and complications in each group were recorded. RESULTS: There were 153
M1 MCA occlusions and 59 M2 MCA occlusions. No statistically significant
difference was found in the rate of mortality (20% in M1 vs 13.6% in M2, p=0.32),
excellent (34.5% vs 37.3%, p=0.75) or good (51% vs 55.9%, p=0.54) clinical
outcomes between the two groups. Infarct volumes (48.4 mL vs 46.2 mL, p=0.62)
were comparable between the two groups, as were the rates of hemorrhagic (3.3% vs
3.4%, p=1.0) and procedural complications (3.3% vs 5.1%, p=0.69). CONCLUSION: Our
data on MT targeting M2 occlusions demonstrates reasonable safety and functional
outcomes. Further randomized clinical trials are needed to clarify which patients
may benefit from MT for M2 occlusions.
PMID- 28705891
TI - Wanted: clinicians with digital and leadership skills.
PMID- 28705893
TI - Evaluation of strategies to communicate harmful and potentially harmful
constituent (HPHC) information through cigarette package inserts: a discrete
choice experiment.
AB - BACKGROUND: The US Food and Drug Administration (FDA) has regulatory authority to
use inserts to communicate with consumers about harmful and potentially harmful
constituents (HPHCs) in tobacco products; however, little is known about the most
effective manner for presenting HPHC information. METHODS: In a discrete choice
experiment, participants evaluated eight choice sets, each of which showed two
cigarette packages from four different brands and tar levels (high vs low),
accompanied by an insert that included between-subject manipulations (ie, listing
of HPHCs vs grouping by disease outcome and numeric values ascribed to HPHCs vs
no numbers) and within-subject manipulations (ie, 1 of 4 warning topics;
statement linking an HPHC with disease vs statement with no HPHC link). For each
choice set, participants were asked: (1) which package is more harmful and (2)
which motivates them to not smoke; each with a 'no difference' option.
Alternative-specific logit models regressed choice on attribute levels. RESULTS:
1212 participants were recruited from an online consumer panel (725 18-29-year
old smokers and susceptible non-smokers and 487 30-64-year-old smokers).
Participants were more likely to endorse high-tar products as more harmful than
low-tar products, with a greater effect when numeric HPHC information was
present. Compared with a simple warning statement, the statement linking HPHCs
with disease encouraged quit motivation. CONCLUSIONS: Numeric HPHC information on
inserts appears to produce misunderstandings that some cigarettes are less
harmful than others. Furthermore, brief narratives that link HPHCs to smoking
related disease may promote cessation versus communications that do not
explicitly link HPHCs to disease.
PMID- 28705894
TI - Genome-wide analysis of facial skeletal regionalization in zebrafish.
AB - Patterning of the facial skeleton involves the precise deployment of thousands of
genes in distinct regions of the pharyngeal arches. Despite the significance for
craniofacial development, how genetic programs drive this regionalization remains
incompletely understood. Here we use combinatorial labeling of zebrafish cranial
neural crest-derived cells (CNCCs) to define global gene expression along the
dorsoventral axis of the developing arches. Intersection of region-specific
transcriptomes with expression changes in response to signaling perturbations
demonstrates complex roles for Endothelin 1 (Edn1) signaling in the intermediate
joint-forming region, yet a surprisingly minor role in ventralmost regions.
Analysis of co-variance across multiple sequencing experiments further reveals
clusters of co-regulated genes, with in situ hybridization confirming the domain
specific expression of novel genes. We then created loss-of-function alleles for
12 genes and uncovered antagonistic functions of two new Edn1 targets,
follistatin a (fsta) and emx2, in regulating cartilaginous joints in the hyoid
arch. Our unbiased discovery and functional analysis of genes with regional
expression in zebrafish arch CNCCs reveals complex regulation by Edn1 and points
to novel candidates for craniofacial disorders.
PMID- 28705895
TI - Asymmetric distribution of hypoxia-inducible factor alpha regulates dorsoventral
axis establishment in the early sea urchin embryo.
AB - Hypoxia signaling is an ancient pathway by which animals can respond to low
oxygen. Malfunction of this pathway disturbs hypoxic acclimation and can result
in various diseases, including cancers. The role of hypoxia signaling in early
embryogenesis remains unclear. Here, we show that in the blastula of the sea
urchin Strongylocentrotus purpuratus, hypoxia-inducible factor alpha (HIFalpha),
the downstream transcription factor of the hypoxia pathway, is localized and
transcriptionally active on the future dorsal side. This asymmetric distribution
is attributable to its oxygen-sensing ability. Manipulations of the HIFalpha
level entrained the dorsoventral axis, as the side with the higher level of
HIFalpha tends to develop into the dorsal side. Gene expression analyses revealed
that HIFalpha restricts the expression of nodal to the ventral side and activates
several genes encoding transcription factors on the dorsal side. We also observed
that intrinsic hypoxic signals in the early embryos formed a gradient, which was
disrupted under hypoxic conditions. Our results reveal an unprecedented role of
the hypoxia pathway in animal development.
PMID- 28705896
TI - Bmp signaling maintains a mesoderm progenitor cell state in the mouse tailbud.
AB - Caudal somites are generated from a pool of progenitor cells located in the
tailbud region. These progenitor cells form the presomitic mesoderm that
gradually differentiates into somites under the action of the segmentation clock.
The signals responsible for tailbud mesoderm progenitor pool maintenance during
axial elongation are still elusive. Here, we show that Bmp signaling is
sufficient to activate the entire mesoderm progenitor gene signature in primary
cultures of caudal mesoderm cells. Bmp signaling acts through the key regulatory
genes brachyury (T) and Nkx1-2 and contributes to the activation of several other
regulators of the mesoderm progenitor gene network. In the absence of Bmp
signaling, tailbud mesoderm progenitor cells acquire aberrant gene expression
signatures of the heart, blood, muscle and skeletal embryonic lineages. Treatment
of embryos with the Bmp inhibitor noggin confirmed the requirement for Bmp
signaling for normal T expression and the prevention of abnormal lineage marker
activation. Together, these results identify Bmp signaling as a non-cell
autonomous signal necessary for mesoderm progenitor cell homeostasis.
PMID- 28705897
TI - Cas9-mediated excision of Nematostella brachyury disrupts endoderm development,
pharynx formation and oral-aboral patterning.
AB - The mesoderm is a key novelty in animal evolution, although we understand little
of how the mesoderm arose. brachyury, the founding member of the T-box gene
family, is a key gene in chordate mesoderm development. However, the brachyury
gene was present in the common ancestor of fungi and animals long before mesoderm
appeared. To explore ancestral roles of brachyury prior to the evolution of
definitive mesoderm, we excised the gene using CRISPR/Cas9 in the diploblastic
cnidarian Nematostella vectensisNvbrachyury is normally expressed in precursors
of the pharynx, which separates endoderm from ectoderm. In knockout embryos, the
pharynx does not form, embryos fail to elongate, and endoderm organization,
ectodermal cell polarity and patterning along the oral-aboral axis are disrupted.
Expression of many genes both inside and outside the Nvbrachyury expression
domain is affected, including downregulation of Wnt genes at the oral pole. Our
results point to an ancient role for brachyury in morphogenesis, cell polarity
and the patterning of both ectodermal and endodermal derivatives along the
primary body axis.
PMID- 28705898
TI - Cellular heterogeneity in the ureteric progenitor niche and distinct profiles of
branching morphogenesis in organ development.
AB - Branching morphogenesis creates arborized epithelial networks. In the mammalian
kidney, an epithelial progenitor pool at ureteric branch tips (UBTs) creates the
urine-transporting collecting system. Using region-specific mouse reporter
strains, we performed an RNA-seq screen, identifying tip- and stalk-enriched gene
sets in the developing collecting duct system. Detailed in situ hybridization
studies of tip-enriched predictions identified UBT-enriched gene sets conserved
between the mouse and human kidney. Comparative spatial analysis of their UBT
niche expression highlighted distinct patterns of gene expression revealing novel
molecular heterogeneity within the UBT progenitor population. To identify kidney
specific and shared programs of branching morphogenesis, comparative expression
studies on the developing mouse lung were combined with in silico analysis of the
developing mouse salivary gland. These studies highlight a shared gene set with
multi-organ tip enrichment and a gene set specific to UBTs. This comprehensive
analysis extends our current understanding of the ureteric branch tip niche.
PMID- 28705899
TI - A novel function for the IkappaB inhibitor Cactus in promoting Dorsal nuclear
localization and activity in the Drosophila embryo.
AB - The evolutionarily conserved Toll signaling pathway controls innate immunity
across phyla and embryonic patterning in insects. In the Drosophila embryo, Toll
is required to establish gene expression domains along the dorsal-ventral axis.
Pathway activation induces degradation of the IkappaB inhibitor Cactus, resulting
in a ventral-to-dorsal nuclear gradient of the NFkappaB effector Dorsal. Here, we
investigate how cactus modulates Toll signals through its effects on the Dorsal
gradient and on Dorsal target genes. Quantitative analysis using a series of loss
and gain-of-function conditions shows that the ventral and lateral aspects of
the Dorsal gradient can behave differently with respect to Cactus fluctuations.
In lateral and dorsal embryo domains, loss of Cactus allows more Dorsal to
translocate to the nucleus. Unexpectedly, cactus loss-of-function alleles
decrease Dorsal nuclear localization ventrally, where Toll signals are high.
Overexpression analysis suggests that this ability of Cactus to enhance Toll
stems from the mobilization of a free Cactus pool induced by the Calpain A
protease. These results indicate that Cactus acts to bolster Dorsal activation,
in addition to its role as a NFkappaB inhibitor, ensuring a correct response to
Toll signals.
PMID- 28705900
TI - Subtypes of primary angiitis of the CNS identified by MRI patterns reflect the
size of affected vessels.
AB - OBJECTIVE: To describe patterns of diagnostic findings, and identify subgroups of
primary angiitis of the central nervous system (PACNS). METHODS: We
retrospectively analysed 31 patients with PACNS. Cases were selected by
predetermined diagnostic criteria and stratified into biopsy-proven and imaging
based PACNS. We compared clinical characteristics, cerebrospinal fluid (CSF)
findings and imaging results including high-resolution vessel wall MRI between
groups. RESULTS: There were 31 cases of PACNS (mean age 45.6 years, 58.1%
female), of whom 17 (55%) were biopsy-proven, 14 (45%) were based on imaging
findings. Patients with a positive biopsy had fewer infarcts (29.4% vs 85.7%,
p=0.003), were more likely to have meningeal and parenchymal contrast enhancement
(76.5% vs 28.6%, p=0.012), were less likely to have abnormal MR angiography
(11.8% vs 100%, p<0.001) and did not show vessel wall enhancement at the time of
diagnosis (0% vs 76.9%, p<0.001). In contrast, patients with imaging-based
diagnosis showed more frequently multiple infarcts and vessel abnormalities, with
vessel wall enhancement in most of the cases. Clinical characteristics and CSF
analysis did not reveal marked differences between groups. INTERPRETATION: Multi
parametric MRI distinguishes two subtypes of PACNS that most likely differ
concerning the affected vessel size. Biopsy-proven PACNS primarily involves
smaller vessels beyond the resolution of vascular imaging, while imaging-based
PACNS affects predominantly medium-sized vessels leading to false-negative biopsy
results. Using distinct MRI patterns may be helpful for selecting patients for
appropriate invasive diagnostic modalities.
PMID- 28705901
TI - Temporal contribution of the platelet body and balloon to thrombin generation.
PMID- 28705902
TI - Long-term risk of cancer development in adult patients with idiopathic aplastic
anemia after treatment with anti-thymocyte globulin.
PMID- 28705903
TI - An immunocompetent patient with a recurrence-free Epstein-Barr virus positive
plasmacytoma possesses robust Epstein-Barr virus specific T-cell responses.
PMID- 28705904
TI - Severe chest pain in an asthmatic patient.
PMID- 28705905
TI - Genome-Wide Transcriptional Dynamics in the Companion Bacterial Symbionts of the
Glassy-Winged Sharpshooter (Cicadellidae: Homalodisca vitripennis) Reveal
Differential Gene Expression in Bacteria Occupying Multiple Host Organs.
AB - The agricultural pest known as the glassy-winged sharpshooter (GWSS) or
Homalodisca vitripennis (Hemiptera: Cicadellidae) harbors two bacterial
symbionts, "Candidatus Sulcia muelleri" and "Ca Baumannia cicadellinicola," which
provide the 10 essential amino acids (EAAs) that are limited in the host plant
sap diet. Although they differ in origin and symbiotic age, both bacteria have
experienced extensive genome degradation resulting from their ancient restriction
to specialized host organs (bacteriomes) that provide cellular support and ensure
vertical transmission. GWSS bacteriomes are of different origins and distinctly
colored red and yellow. While Sulcia occupies the yellow bacteriome, Baumannia
inhabits both. Aside from genomic predictions, little is currently known about
the cellular functions of these bacterial symbionts, particularly whether
Baumannia in different bacteriomes perform different roles in the symbiosis. To
address these questions, we conducted a replicated, strand-specific RNA-seq
experiment to assay global gene expression patterns in Sulcia and Baumannia
Despite differences in genomic capabilities, the symbionts exhibit similar
profiles of their most highly expressed genes, including those involved in
nutrition synthesis and protein stability (chaperonins dnaK and groESL) that
likely aid impaired proteins. Baumannia populations in separate bacteriomes
differentially express genes enriched in essential nutrient synthesis, including
EAAs (histidine and methionine) and B vitamins (biotin and thiamine). Patterns of
differential gene expression further reveal complexity in methionine synthesis.
Baumannia's capability to differentially express genes is unusual, as ancient
symbionts lose the capability to independently regulate transcription. Combined
with previous microscopy, our results suggest that the GWSS may rely on distinct
Baumannia populations for essential nutrition and vertical transmission.
PMID- 28705906
TI - Hypertensive disorders of pregnancy.
PMID- 28705908
TI - Importance of kynurenine in pulmonary hypertension.
AB - The tryptophan metabolite kynurenine is significantly increased in pulmonary
arterial hypertension (PAH) patients, and it is a potent vasodilator of systemic
arteries. Our aim was to investigate the role of kynurenine in the pulmonary
circulation. Serum tryptophan, kynurenine, and kynurenic acid levels were
measured in 20 idiopathic PAH (IPAH) patients, 20 healthy controls, and 20
patients with chronic lung disease or metabolic syndrome without PH. Laser
dissected pulmonary arteries from IPAH and control lungs were tested for the
expression of indoleamine-2, 3-dioxygenase (IDO), the rate-limiting enzyme for
the conversion from tryptophan to kynurenine. Acute effects of kynurenine were
tested in pulmonary vascular preparations, two different models of chronic
pulmonary hypertension (PH), and in human pulmonary arterial smooth muscle cells
(hPASMCs). In IPAH vs. control serum, kynurenine was significantly elevated (3.6
+/- 0.2 vs. 2.6 +/- 0.1 uM, P < 0.0001), and strongly associated with PH (area
under the curve = 0.86), but kynurenine levels were not elevated in lung disease
and metabolic syndrome. Among all investigated tryptophan metabolites, kynurenine
displayed the strongest correlation with mean pulmonary arterial pressure (mPAP)
(rho: 0.770, P < 0.0001). Tryptophan was significantly decreased in IPAH lungs;
however, IDO expression was not changed. In hPASMCs, kynurenine increased both
cAMP and cGMP; in intrapulmonary arteries, it relaxed the preconstriction via
NO/cGMP and cAMP pathways, and in two models of established PH, it acutely
decreased the mPAP. Our data suggest that kynurenine elevation might be
specifically associated with mPAP; kynurenine acts on hPASMCs in synergy with NO
and exerts acute pulmonary vasodilatation in chronic PH models. Kynurenine might
provide both a new biomarker and a new therapeutic option for PH.
PMID- 28705909
TI - TGF-beta inhibits alveolar protein transport by promoting shedding, regulated
intramembrane proteolysis, and transcriptional downregulation of megalin.
AB - Disruption of the alveolar-capillary barrier is a hallmark of acute respiratory
distress syndrome (ARDS) that leads to the accumulation of protein-rich edema in
the alveolar space, often resulting in comparable protein concentrations in
alveolar edema and plasma and causing deleterious remodeling. Patients who
survive ARDS have approximately three times lower protein concentrations in the
alveolar edema than nonsurvivors; thus the ability to remove excess protein from
the alveolar space may be critical for a positive outcome. We have recently shown
that clearance of albumin from the alveolar space is mediated by megalin, a 600
kDa transmembrane endocytic receptor and member of the low-density lipoprotein
receptor superfamily. In the currents study, we investigate the molecular
mechanisms by which transforming growth factor-beta (TGF-beta), a key molecule of
ARDS pathogenesis, drives downregulation of megalin expression and function. TGF
beta treatment led to shedding and regulated intramembrane proteolysis of megalin
at the cell surface and to a subsequent increase in intracellular megalin COOH
terminal fragment abundance resulting in transcriptional downregulation of
megalin. Activity of classical protein kinase C enzymes and gamma-secretase was
required for the TGF-beta-induced megalin downregulation. Furthermore, TGF-beta
induced shedding of megalin was mediated by matrix metalloproteinases (MMPs)-2,
9, and -14. Silencing of either of these MMPs stabilized megalin at the cell
surface after TGF-beta treatment and restored normal albumin transport. Moreover,
a direct interaction of megalin with MMP-2 and -14 was demonstrated, suggesting
that these MMPs may function as novel sheddases of megalin. Further understanding
of these mechanisms may lead to novel therapeutic approaches for the treatment of
ARDS.
PMID- 28705910
TI - Fatigability, Exercise Intolerance, and Abnormal Skeletal Muscle Energetics in
Heart Failure.
AB - BACKGROUND: Among central and peripheral factors contributing to exercise
intolerance (EI) in heart failure (HF), the extent to which skeletal muscle (SM)
energy metabolic abnormalities occur and contribute to EI and increased
fatigability in HF patients with reduced or preserved ejection fraction (HFrEF
and HFpEF, respectively) are not known. An energetic plantar flexion exercise
fatigability test and magnetic resonance spectroscopy were used to probe the
mechanistic in vivo relationships among SM high-energy phosphate concentrations,
mitochondrial function, and EI in HFrEF and HFpEF patients and in healthy
controls. METHODS AND RESULTS: Resting SM high-energy phosphate concentrations
and ATP flux rates were normal in HFrEF and HFpEF patients. Fatigue occurred at
similar SM energetic levels in all subjects, consistent with a common SM
energetic limit. Importantly, HFrEF New York Heart Association class II-III
patients with EI and high fatigability exhibited significantly faster rates of
exercise-induced high-energy phosphate decline than did HFrEF patients with low
fatigability (New York Heart Association class I), despite similar left
ventricular ejection fractions. HFpEF patients exhibited severe EI, the most
rapid rates of high-energy phosphate depletion during exercise, and impaired
maximal oxidative capacity. CONCLUSIONS: Symptomatic fatigue during plantar
flexion exercise occurs at a common energetic limit in all subjects. HFrEF and
HFpEF patients with EI and increased fatigability manifest early, rapid exercise
induced declines in SM high-energy phosphates and reduced oxidative capacity
compared with healthy and low-fatigability HF patients, suggesting that SM
metabolism is a potentially important target for future HF treatment strategies.
PMID- 28705911
TI - Making the Case for Skeletal Muscle Myopathy and Its Contribution to Exercise
Intolerance in Heart Failure With Preserved Ejection Fraction.
PMID- 28705912
TI - Editor's Perspective.
PMID- 28705913
TI - Interpretation Modalities Used on Family-Centered Rounds: Perspectives of Spanish
Speaking Families.
AB - BACKGROUND AND OBJECTIVES: Limited-English-proficient (LEP) patients and families
are at risk for worse hospital outcomes due to impaired communication. Family
centered rounds (FCR) have become the preferred format for information sharing
among providers and families at pediatric institutions. However, there are
limited data on FCR among LEP families, particularly regarding interpretation
type. We sought to examine the relationships between interpretation type and FCR
satisfaction and efficacy among Spanish-speaking families, the fastest growing
LEP population in pediatric hospitals. METHODS: Spanish speakers admitted to
general pediatrics units over a period of 16 months were identified on admission.
A bilingual research assistant observed FCR and completed an observation tool,
including interpreter type. After FCR, the research assistant interviewed
families, collecting parent demographics, FCR experience, and interpreter
satisfaction. Associations between interpretation type and satisfaction as well
as interpretation type and understanding were tested by using chi2 analyses.
RESULTS: We studied 124 families over 16 months. Most respondents were patients'
mothers (84%), born in Mexico (76%), had grade school education (56%), and spoke
limited English (96%). Overall, 83 (73%) reported the interpreter services
improved their understanding of their child's medical condition. Interpreter type
was significantly associated with family satisfaction with FCR; specifically, an
in-person hospital interpreter or video interpreter was associated with complete
caregiver satisfaction (P = .005). CONCLUSIONS: Spanish speakers report higher
satisfaction with face-to-face interpreters during FCR, including in-person and
video, compared with telephonic interpreters. Video interpretation via iPad
during FCR may be a valuable and accessible approach to improve communication in
the care of hospitalized children.
PMID- 28705914
TI - London should ban all diesel vehicles.
PMID- 28705915
TI - Microarray analysis of bone marrow lesions in osteoarthritis demonstrates
upregulation of genes implicated in osteochondral turnover, neurogenesis and
inflammation.
AB - OBJECTIVE: Bone marrow lesions (BMLs) are well described in osteoarthritis (OA)
using MRI and are associated with pain, but little is known about their
pathological characteristics and gene expression. We evaluated BMLs using novel
tissue analysis tools to gain a deeper understanding of their cellular and
molecular expression. METHODS: We recruited 98 participants, 72 with advanced OA
requiring total knee replacement (TKR), 12 with mild OA and 14 non-OA controls.
Participants were assessed for pain (using Western Ontario and McMaster
Universities Osteoarthritis Index (WOMAC)) and with a knee MRI (using MOAKS).
Tissue was then harvested at TKR for BML analysis using histology and tissue
microarray. RESULTS: The mean (SD) WOMAC pain scores were significantly increased
in advanced OA 59.4 (21.3) and mild OA 30.9 (20.3) compared with controls 0.5
(1.28) (p<0.0001). MOAKS showed all TKR tissue analysed had BMLs, and within
these lesions, bone marrow volume was starkly reduced being replaced by dense
fibrous connective tissue, new blood vessels, hyaline cartilage and
fibrocartilage. Microarray comparing OA BML and normal bone found a significant
difference in expression of 218 genes (p<0.05). The most upregulated genes
included stathmin 2, thrombospondin 4, matrix metalloproteinase 13 and
Wnt/Notch/catenin/chemokine signalling molecules that are known to constitute
neuronal, osteogenic and chondrogenic pathways. CONCLUSION: Our study is the
first to employ detailed histological analysis and microarray techniques to
investigate knee OA BMLs. BMLs demonstrated areas of high metabolic activity
expressing pain sensitisation, neuronal, extracellular matrix and proinflammatory
signalling genes that may explain their strong association with pain.
PMID- 28705916
TI - Biodistribution and Dosimetry of 18F-Meta-Fluorobenzylguanidine: A First-in-Human
PET/CT Imaging Study of Patients with Neuroendocrine Malignancies.
AB - 123I-meta-iodobenzylguanidine (123I-MIBG) imaging is currently a mainstay in the
evaluation of many neuroendocrine tumors, especially neuroblastoma. 123I-MIBG
imaging has several limitations that can be overcome by the use of a PET agent.
18F-meta-fluorobenzylguanidine (18F-MFBG) is a PET analog of MIBG that may allow
for single-day, high-resolution quantitative imaging. We conducted a first-in
human study of 18F-MFBG PET imaging to evaluate the safety, feasibility,
pharmacokinetics, and dosimetry of 18F-MFBG in neuroendocrine tumors (NETs).
Methods: Ten patients (5 with neuroblastoma and 5 with
paraganglioma/pheochromocytoma) received 148-444 MBq (4-12mCi) of 18F-MFBG
intravenously followed by serial whole-body imaging at 0.5-1, 1-2, and 3-4 after
injection. Serial blood samples (a total of 6) were also obtained starting at 5
min after injection to as late as 4 h after injection; whole-body distribution
and blood clearance data, lesion uptake, and normal-tissue uptake were
determined, and radiation-absorbed doses to normal organs were calculated using
OLINDA. Results: No side effects were seen in any patient after 18F-MFBG
injection. Tracer distribution showed prominent activity in the blood pool,
liver, and salivary glands that decreased with time. Mild uptake was seen in the
kidneys and spleen, which also decreased with time. Urinary excretion was
prominent, with an average of 45% of the administered activity in the bladder by
1 h after injection; whole-body clearance was monoexponential, with a mean
biologic half-life of 1.95 h, whereas blood clearance was biexponential, with a
mean biologic half-life of 0.3 h (58%) for the rapid alpha phase and 6.1 h (42%)
for the slower beta phase. The urinary bladder received the highest radiation
dose with a mean absorbed dose of 0.186 +/- 0.195 mGy/MBq. The mean total-body
dose was 0.011 +/- 0.011 mGy/MBq, and the effective dose was 0.023 +/- 0.012
mSv/MBq. Both skeletal and soft-tissue lesions were visualized with high
contrast. The SUVmax (mean +/- SD ) of lesions at 1-2 h after injection was 8.6
+/- 9.6. Conclusion: Preliminary data show that 18F-MFBG imaging is safe and has
favorable biodistribution and kinetics with good targeting of lesions. PET
imaging with 18F-MFBG allows for same-day imaging of NETs. 18F-MFBG appears
highly promising for imaging of patients with NETs, especially children with
neuroblastoma.
PMID- 28705917
TI - Curative Multicycle Radioimmunotherapy Monitored by Quantitative SPECT/CT-Based
Theranostics, Using Bispecific Antibody Pretargeting Strategy in Colorectal
Cancer.
AB - Radioimmunotherapy of solid tumors using antibody-targeted radionuclides has been
limited by low therapeutic indices (TIs). We recently reported a novel 3-step
pretargeted radioimmunotherapy (PRIT) strategy based on a glycoprotein A33
(GPA33)-targeting bispecific antibody and a small-molecule radioactive hapten, a
complex of 177Lu and S-2-(4-aminobenzyl)-1,4,7,10-tetraazacyclododecane
tetraacetic acid (177Lu-DOTA-Bn), that leads to high TIs for radiosensitive
tissues such as blood (TI = 73) and kidney (TI = 12). We tested our hypothesis
that a fractionated anti-GPA33 DOTA-PRIT regimen calibrated to deliver a
radiation absorbed dose to tumor of more than 100 Gy would lead to a high
probability of tumor cure while being well tolerated by nude mice bearing
subcutaneous GPA33-positive SW1222 xenografts. Methods: We treated groups of nude
mice bearing 7-d-old SW1222 xenografts with a fractionated 3-cycle anti-GPA33
DOTA-PRIT regimen (total administered 177Lu-DOTA-Bn activity, 167 MBq/mouse;
estimated radiation absorbed dose to tumor, 110 Gy). In randomly selected mice
undergoing treatment, serial SPECT/CT imaging was used to monitor treatment
response and calculate radiation absorbed doses to tumor. Necropsy was done on
surviving animals 100-200 d after treatment to determine frequency of cure and
assess select normal tissues for treatment-related histopathologies. Results:
Rapid exponential tumor progression was observed in control treatment groups
(i.e., no treatment or 177Lu-DOTA-Bn only), leading to euthanasia due to
excessive tumor burden, whereas 10 of 10 complete responses were observed for the
DOTA-PRIT-treated animals within 30 d. Treatment was well tolerated, and 100%
histologic cure was achieved in 9 of 9 assessable animals without detectable
radiation damage to critical organs, including bone marrow and kidney. Radiation
absorbed doses to tumor derived from SPECT/CT (102 Gy) and from biodistribution
(110 Gy) agreed to within 6.9%. Of the total dose of approximately 100 Gy, the
first dose contributes 30%, the second dose 60%, and the third dose 10%.
Conclusion: In a GPA33-positive human colorectal cancer xenograft mouse model, we
validated a SPECT/CT-based theranostic PRIT regimen that led to 100% complete
responses and 100% cures without any treatment-related toxicities, based on high
TIs for radiosensitive tissues. These studies support the view that anti-GPA33
DOTA-PRIT will be a potent radioimmunotherapy regimen for GPA33-positive
colorectal cancer tumors in humans.
PMID- 28705918
TI - In Vivo Quantification of ERbeta Expression by Pharmacokinetic Modeling: Studies
with 18F-FHNP PET.
AB - The estrogen receptor (ER) is a target for endocrine therapy in breast cancer
patients. Individual quantification of ERalpha and ERbeta expression, rather than
total ER levels, might enable better prediction of the response to treatment. We
recently developed the tracer 2-18F-fluoro-6-(6-hydroxynaphthalen-2-yl)pyridin-3
ol (18F-FHNP) for assessment of ERbeta levels with PET. In the current study, we
investigated several pharmacokinetic analysis methods to quantify changes in
ERbeta availability with 18F-FHNP PET. Methods: Male nude rats were
subcutaneously inoculated in the shoulder with ERalpha/ERbeta-expressing SKOV3
human ovarian cancer cells. Two weeks after tumor inoculation, a dynamic 18F-FHNP
PET scan with arterial blood sampling was acquired from rats treated with vehicle
or various concentrations of estradiol (nonspecific ER agonist) or genistein
(ERbeta-selective agonist). Different pharmacokinetic models were applied to
quantify ERbeta availability in the tumor. Results: Irreversible-uptake
compartmental models fitted the kinetics of 18F-FHNP uptake better than
reversible models. The irreversible 3-tissue-compartment model, which included
both the parent and the metabolite input function, gave results comparable to
those of the irreversible 2-tissue-compartment model with only a parent input
function, indicating that radioactive metabolites contributed little to the tumor
uptake. Patlak graphical analysis gave metabolic rates (Ki, the irreversible
uptake rate constant) comparable to compartment modeling. The Ki values
correlated well with ERbeta expression but not with ERalpha, confirming that Ki
is a suitable parameter to quantify ERbeta expression. SUVs at 60 min after
tracer injection also correlated (r2 = 0.47; P = 0.04) with ERbeta expression. A
reduction in 18F-FHNP tumor uptake and Ki values was observed in the presence of
estradiol or genistein. Conclusion:18F-FHNP PET enables assessment of ERbeta
availability in tumor-bearing rats. The most suitable parameter to quantify
ERbeta expression is the Ki However, a simplified static imaging protocol for
determining the SUVs can be applied to assess ERbeta levels.
PMID- 28705919
TI - Time Courses of Cortical Glucose Metabolism and Microglial Activity Across the
Life Span of Wild-Type Mice: A PET Study.
AB - Contrary to findings in the human brain, 18F-FDG PET shows cerebral
hypermetabolism of aged wild-type (WT) mice relative to younger animals,
supposedly due to microglial activation. Therefore, we used dual-tracer small
animal PET to examine directly the link between neuroinflammation and
hypermetabolism in aged mice. Methods: WT mice (5-20 mo) were investigated in a
cross-sectional design using 18F-FDG (n = 43) and translocator protein (TSPO)
(18F-GE180; n = 58) small-animal PET, with volume-of-interest and voxelwise
analyses. Biochemical analysis of plasma cytokine levels and immunohistochemical
confirmation of microglial activity were also performed. Results: Age-dependent
cortical hypermetabolism in WT mice relative to young animals aged 5 mo peaked at
14.5 mo (+16%, P < 0.001) and declined to baseline at 20 mo. Similarly, cortical
TSPO binding increased to a maximum at 14.5 mo (+15%, P < 0.001) and remained
high to 20 mo, resulting in an overall correlation between 18F-FDG uptake and
TSPO binding (R = 0.69, P < 0.005). Biochemical and immunohistochemical analyses
confirmed the TSPO small-animal PET findings. Conclusion: Age-dependent
neuroinflammation is associated with the controversial observation of cerebral
hypermetabolism in aging WT mice.
PMID- 28705920
TI - Nephron Remodeling Underlies Hyperkalemia in Familial Hyperkalemic Hypertension.
PMID- 28705921
TI - Apixaban may have lower risk of GI bleeding compared with dabigatran and
rivaroxaban in patients with atrial fibrillation.
PMID- 28705922
TI - The Cochrane Collaboration withdraws a review on methylphenidate for adults with
attention deficit hyperactivity disorder.
AB - A Cochrane systematic review on immediate-release methylphenidate for adults with
attention deficit hyperactivity disorder (ADHD) was withdrawn from the Cochrane
Library on 26 May 2016 after substantial criticism of its methods and flawed
conclusions. Retraction of scientific papers on this basis is unusual but can be
necessary. We provide a summary of the criticism that led to the withdrawal. We
detail the methodological flaws of the withdrawn Cochrane systematic review and
general issues of bias and shortcomings of the included ADHD trials: cross-over
designs compared with parallel-group designs, exclusion of participants with
psychiatric comorbidity, absence of 'functional outcomes' and use of clinical
outcomes with limited relevance, short trial duration and small trial
populations, broken blinding caused by easily recognisable side effects,
combining outcome assessments by trial investigators and participants, outcome
reporting bias, poor evaluation of cardiovascular and psychiatric harms and
conflicts of interest of trialists and systematic reviewers. The withdrawal of
the Cochrane systematic review signals recognition of previous unreliable
clinical ADHD research. We conclude that clinical trials of immediate-release
methylphenidate in adults with ADHD are of very low quality. We urgently need
well-conducted long-term trials free of bias to assess the benefits and harms of
central stimulant treatment in adult ADHD.
PMID- 28705924
TI - End-of-life chemotherapy: a prisoner's dilemma?
PMID- 28705923
TI - Maternal and female fetal testosterone levels are associated with maternal age
and gestational weight gain.
AB - OBJECTIVE: Prenatal androgen exposure has been suggested to play a role in
polycystic ovary syndrome. Given the limited information on what maternal
characteristics influence maternal testosterone levels, and the even less
explored routes by which female fetus androgen exposure would occur, the aim of
this study was to investigate the impact of maternal age, BMI, weight gain,
depressed mood and aromatase SNPs on testosterone levels in maternal serum and
amniotic fluid of female fetuses. METHODS: Blood samples from pregnant women (n =
216) obtained in gestational weeks 35-39, and pre-labor amniotic fluid samples
from female fetuses (n = 56), taken at planned Caesarean section or in
conjunction with amniotomy for induction of labor, were analyzed. Maternal serum
testosterone and amniotic fluid testosterone and cortisol were measured by tandem
mass spectrometry. RESULTS: Multiparity (beta = -0.28, P < 0.001), self-rated
depression (beta = 0.26, P < 0.001) and weight gain (beta = 0.18, P < 0.05) were
independent explanatory factors for the maternal total testosterone levels.
Maternal age (beta = -0.34, P < 0.001), weight gain (beta = 0.19, P < 0.05) and
amniotic fluid cortisol levels (beta = 0.44, P < 0.001) were independent
explanatory factors of amniotic fluid testosterone in female fetuses, explaining
64.3% of the variability in amniotic fluid testosterone. WIDER IMPLICATIONS OF
THE FINDINGS: Young maternal age and excessive maternal weight gain may increase
the prenatal androgen exposure of female fetuses. Further studies are needed to
explore this finding.
PMID- 28705925
TI - Management of hiccups in palliative care patients.
AB - Persistent hiccups are a frustrating experience for palliative care patients, and
can have a profound impact on their quality of life. This article provides an
evidence-based approach overview of the causes and treatment of this not
infrequently debilitating condition for such patients, with a management
algorithm. In situations where no readily reversible cause is identified, or
where simple physical manoeuvres, such as breath holding have failed, a
systematic approach is required. Hiccups can be broadly divided into central and
peripheral types. These respond differently to pharmacological intervention. The
drug of choice for central causes of persistent hiccups is baclofen, with
metoclopramide recommended as the first choice for peripheral causes. Midazolam
may be useful in cases of terminal illness. Interventional procedures such as
vagal or phrenic nerve block or stimulation should be considered in patients who
are refractory to medications. The management of persistent hiccups still
presents an ongoing clinical challenge however, requiring further research on
pathophysiology and treatment strategies. Multinational randomised controlled
trials to evaluate and compare both current and new medications or procedures to
better manage this difficult condition are suggested as a means of reaching this
goal.
PMID- 28705926
TI - Incidental Findings on Myocardial Perfusion SPECT Images.
AB - Myocardial perfusion SPECT plays a crucial role in the diagnosis of coronary
artery disease, providing a noninvasive tool to monitor ischemia and infarction.
The findings can have a profound impact on diagnosis and management in these
patients. However, incidental noncardiac findings on myocardial perfusion SPECT
images can also affect management. These noncardiac subtleties are most often
detected on the rotating raw SPECT images, which are often overlooked. The intent
of this pictorial essay is to illustrate several subtle noncardiac abnormalities
within nuclear cardiac imaging that can have an impact on patient management and
follow-up.
PMID- 28705927
TI - Incidence of Brain Metastases on Follow-up 18F-FDG PET/CT Scans of Non-Small Cell
Lung Cancer Patients: Should We Include the Brain?
AB - The brain is the most common site of distant metastasis from lung cancer. Thus,
MRI of the brain at initial staging is routinely performed, but if this
examination is negative a follow-up examination is often not performed. This
study evaluates the incidence of asymptomatic brain metastases in non-small cell
lung cancer patients detected on follow-up 18F-FDG PET/CT scans. Methods: In this
Institutional Review Board-approved retrospective review, all vertex to thigh 18F
FDG PET/CT scans in patients with all subtypes of lung cancer from August 2014 to
August 2016 were reviewed. A total of 1,175 18F-FDG PET/CT examinations in 363
patients were reviewed. Exclusion criteria included brain metastases on initial
staging, histologic subtype of small-cell lung cancer, and no follow-up 18F-FDG
PET/CT examinations. After our exclusion criteria were applied, a total of 809
follow-up 18F-FDG PET/CT scans in 227 patients were included in the final
analysis. The original report of each 18F-FDG PET/CT study was reviewed for the
finding of brain metastasis. The finding of a new brain metastasis prompted a
brain MRI, which was reviewed to determine the accuracy of the 18F-FDG PET/CT.
Results: Five of 227 patients with 809 follow-up 18F-FDG PET/CT scans reviewed
were found to have incidental brain metastases. The mean age of the patients with
incidental brain metastasis was 68 y (range, 60-77 y). The mean time from initial
diagnosis to time of detection of incidental brain metastasis was 36 mo (range,
15-66 mo). When MRI was used as the gold standard, our false-positive rate was
zero. Conclusion: By including the entire head during follow-up 18F-FDG PET/CT
scans of patients with non-small cell lung cancer, brain metastases can be
detected earlier while still asymptomatic. But, given the additional scan time,
radiation, and low incidence of new brain metastases in asymptomatic patients,
the cost-to-benefit ratio should be weighed by each institution.
PMID- 28705928
TI - Miniaturized Radiochemical Purity Testing for 99mTc-HMPAO, 99mTc-HMDP, and 99mTc
Tetrofosmin.
AB - Quick methods are functional in clinical practice to ensure the fastest
availability of radiopharmaceuticals. For this purpose, we investigated the
radiochemical purity of the widely used 99mTc-hydroxymethylene diphosphonate,
99mTc-hexamethylpropyleneamine oxime, and 99mTc-tetrofosmin by reducing time as
compared with the manufacturer's method. Methods: We applied a miniaturized
chromatographic method with a reduced strip development from 18 cm to 9 cm for
all 3 radiopharmaceuticals. The specific support medium and solvent system of the
manufacturer's methods was kept unchanged for 99mTc-hydroxymethylene
diphosphonate and 99mTc-tetrofosmin, whereas for 99mTc-hexamethylpropyleneamine
oxime the instant thin-layer chromatography (ITLC) polysilicic gel (silicic acid
[SA]) was replaced with a monosilicic gel (silicic gel [SG]) in the
chromatographic system that uses methyl ethyl ketone as solvent. The method was
applied and compared with the routine ITLC insert method in a total of 30 batches
for each radiopharmaceutical. The precision of repeated tests was determined by
comparison with the results of 10 replications on the same batch. Small volumes
of concentrated 99mTcO4-, and 99mTc-albumin nanocolloid were used to produce
potential radiochemical impurities. Correlation between the quick methods and the
insert methods was analyzed using a nonparametric 2-tailed test and a 2 * 2
contingency table with the associated Fisher exact test to evaluate sensitivity
and specificity. A receiver-operating-characteristic analysis was performed to
evaluate the best cutoff. Results: The percentage radiochemical purity of the
quick methods agreed with the standard chromatography procedures. We found that
99mTcO4 and colloidal impurities are not the only common radiochemical impurities
with 99mTc-tetrofosmin, and shortening of the ITLC strip with respect to the
manufacturer's method will worsen system resolution and may produce inaccuracy.
Conclusion: The miniaturized methods we described represent a fast and reliable
alternative for 99mTc-exametazime and 99mTc-oxidronate quality control, with the
upper cutoff for acceptable radiochemical purity values being 84% and 95%,
respectively. For 99mTc-tetrofosmin radiochemical purity testing, a longer strip
as described in the standard method is warranted.
PMID- 28705929
TI - Use of 99mTc-Tilmanocept as a Single Agent for Sentinel Lymph Node Identification
in Breast Cancer: A Retrospective Pilot Study.
AB - 99mTc-tilmanocept received recent Food and Drug Administration approval for
lymphatic mapping in 2013. However, to our knowledge, no prior studies have
evaluated the use of 99mTc-tilmanocept as a single agent in sentinel lymph node
(SLN) biopsy in breast cancer. Methods: We executed this retrospective pilot
study to assess the ability of 99mTc-tilmanocept to identify sentinel nodes as a
single agent in clinically node-negative breast cancer patients. Patients
received a single intradermal injection overlying the tumor of either 18.5 MBq
(0.5 mCi) of 99mTc-tilmanocept on the day of surgery or 74.0 MBq (2.0 mCi) on the
day before surgery by a radiologist. Immediate 3-view lymphoscintigraphy was
performed. Intraoperatively, SLNs were identified with a portable gamma-probe. A
node was classified as hot if the count (per second) of the node was more than 3
times the background count. Descriptive statistics are reported. Results:
Nineteen patients underwent SLN biopsy with single-agent 99mTc-tilmanocept.
Immediate lymphoscintigraphy identified at least 1 sentinel node in 13 of 17
patients (76.5%). Intraoperatively, at least 1 (mean, 1.7 +/- 0.8; range, 1-3)
hot node was identified in all patients. Three patients (15.8%) had 1 disease
positive SLN. Conclusion: In this small, retrospective pilot study, 99mTc
tilmanocept performed well as a single agent for intraoperative sentinel node
identification in breast cancer. A larger, randomized clinical trial is warranted
to compare 99mTc-tilmanocept as a single agent with other radiopharmaceuticals
for sentinel node identification in breast cancer.
PMID- 28705930
TI - Influence of Attenuation Correction by Brain Perfusion SPECT/CT Using a Simulated
Abnormal Bone Structure: Comparison Between Chang and CT Methods.
AB - Brain perfusion SPECT has physical phenomena such as attenuation, scatter, and
degradation of resolution that impair accuracy on data acquisition. Chang and CT
methods have spread application for attenuation correction (AC) and indicate the
utility of AC using a brain phantom without a bone or with a normal bone
structure. However, nonuniform AC of an abnormal bone structure such as
postoperative bone defect after burr-hole surgery has not yet been evaluated.
Therefore, we evaluated the influence of nonuniform AC of an abnormal bone
structure between the 2 AC methods. Methods: We created 5 brain phantoms
simulating an abnormal bone structure such as frontal, occipital, and right
temporal bone defects as well as with and without a bone, which compared the
influence among 3-dimensional ordered-subset expectation maximization (OSEM)
incorporating scatter, attenuation, and resolution recovery corrections, and
obtained 3 reconstruction processing images: OSEM (non-AC; NAC), OSEM (Chang),
and OSEM (CTAC). The average counts of the 5 brain phantoms by OSEM (NAC), OSEM
(Chang), and OSEM (CTAC) were evaluated by a count profile curve and counts ratio
in the region of interest. Results: The counts of OSEM (NAC) and OSEM (Chang)
with a bone were approximately 7% higher than those without a bone, whereas OSEM
(CTAC) had a similar count ratio. The count ratio of frontal or occipital lobes
with a bone defect on both OSEM (NAC) and OSEM (Chang) was 5%-10% higher than
that in frontal or occipital lobes without a bone defect; however, OSEM (CTAC)
had nearly identical frontal or occipital lobes with and without a bone defect.
Conclusion: We conducted a phantom study simulated with and without a bone defect
to demonstrate the influence of brain counts between 2 different AC methods.
Although the Chang method did not correct the influence of the bone defect due to
the use of a uniform attenuation coefficient, the CTAC method correctly conducted
AC regardless of the presence of a bone defect.
PMID- 28705931
TI - Proof of Concept: Design and Initial Evaluation of a Device to Measure
Gastrointestinal Transit Time.
AB - Chronic constipation and gastrointestinal motility disorders constitute a large
part of a gastroenterology practice and have a significant impact on a patient's
quality of life and lifestyle. In most cases, medications are prescribed to
alleviate symptoms without there being an objective measurement of response.
Commonly used investigations of gastrointestinal transit times are currently
limited to radiopaque markers or electronic capsules. Repeated use of these
techniques is limited because of the radiation exposure and the significant cost
of the devices. We present the proof of concept for a new device to measure
gastrointestinal transit time using commonly available and inexpensive materials
with only a small amount of radiotracer. Methods: We assembled gelatin capsules
containing a 67Ga-citrate-radiolabeled grain of rice embedded in paraffin for use
as a point-source transit device. It was tested for stability in vitro and
subsequently was given orally to 4 healthy volunteers and 10 patients with
constipation or diarrhea. Imaging was performed at regular intervals until the
device was excreted. Results: The device remained intact and visible as a point
source in all subjects until excretion. When used along with a diary of bowel
movement times and dates, the device could determine the total transit time. The
device could be visualized either alone or in combination with a barium small
bowel follow-through study or a gastric emptying study. Conclusion: The use of a
point-source transit device for the determination of gastrointestinal transit
time is a feasible alternative to other methods. The device is inexpensive and
easy to assemble, requires only a small amount of radiotracer, and remains inert
throughout the gastrointestinal tract, allowing for accurate determination of
gastrointestinal transit time. Further investigation of the device is required to
establish optimum imaging parameters and reference values. Measurements of
gastrointestinal transit time may be useful in managing patients with dysmotility
and in selecting the appropriate pharmaceutical treatment.
PMID- 28705932
TI - Use of a neutralizing antibody helps identify structural features critical for
binding of Clostridium difficile toxin TcdA to the host cell surface.
AB - Clostridium difficile is a clinically significant pathogen that causes mild-to
severe (and often recurrent) colon infections. Disease symptoms stem from the
activities of two large, multidomain toxins known as TcdA and TcdB. The toxins
can bind, enter, and perturb host cell function through a multistep mechanism of
receptor binding, endocytosis, pore formation, autoproteolysis, and
glucosyltransferase-mediated modification of host substrates. Monoclonal
antibodies that neutralize toxin activity provide a survival benefit in
preclinical animal models and prevent recurrent infections in human clinical
trials. However, the molecular mechanisms involved in these neutralizing
activities are unclear. To this end, we performed structural studies on a
neutralizing monoclonal antibody, PA50, a humanized mAb with both potent and
broad-spectrum neutralizing activity, in complex with TcdA. Electron microscopy
imaging and multiangle light-scattering analysis revealed that PA50 binds
multiple sites on the TcdA C-terminal combined repetitive oligopeptides (CROPs)
domain. A crystal structure of two PA50 Fabs bound to a segment of the TcdA CROPs
helped define a conserved epitope that is distinct from previously identified
carbohydrate-binding sites. Binding of TcdA to the host cell surface was directly
blocked by either PA50 mAb or Fab and suggested that receptor blockade is the
mechanism by which PA50 neutralizes TcdA. These findings highlight the importance
of the CROPs C terminus in cell-surface binding and a role for neutralizing
antibodies in defining structural features critical to a pathogen's mechanism of
action. We conclude that PA50 protects host cells by blocking the binding of TcdA
to cell surfaces.
PMID- 28705933
TI - Two functionally distinct NADP+-dependent ferredoxin oxidoreductases maintain the
primary redox balance of Pyrococcus furiosus.
AB - Electron bifurcation has recently gained acceptance as the third mechanism of
energy conservation in which energy is conserved through the coupling of
exergonic and endergonic reactions. A structure-based mechanism of bifurcation
has been elucidated recently for the flavin-based enzyme NADH-dependent
ferredoxin NADP+ oxidoreductase I (NfnI) from the hyperthermophillic archaeon
Pyrococcus furiosus. NfnI is thought to be involved in maintaining the cellular
redox balance, producing NADPH for biosynthesis by recycling the two other
primary redox carriers, NADH and ferredoxin. The P. furiosus genome encodes an
NfnI paralog termed NfnII, and the two are differentially expressed, depending on
the growth conditions. In this study, we show that deletion of the genes encoding
either NfnI or NfnII affects the cellular concentrations of NAD(P)H and
particularly NADPH. This results in a moderate to severe growth phenotype in
deletion mutants, demonstrating a key role for each enzyme in maintaining redox
homeostasis. Despite their similarity in primary sequence and cofactor content,
crystallographic, kinetic, and mass spectrometry analyses reveal that there are
fundamental structural differences between the two enzymes, and NfnII does not
catalyze the NfnI bifurcating reaction. Instead, it exhibits non-bifurcating
ferredoxin NADP oxidoreductase-type activity. NfnII is therefore proposed to be a
bifunctional enzyme and also to catalyze a bifurcating reaction, although its
third substrate, in addition to ferredoxin and NADP(H), is as yet unknown.
PMID- 28705934
TI - Gq pathway regulates proximal C-type lectin-like receptor-2 (CLEC-2) signaling in
platelets.
AB - Platelets play a key role in the physiological hemostasis or pathological process
of thrombosis. Rhodocytin, an agonist of the C-type lectin-like receptor-2 (CLEC
2), elicits powerful platelet activation signals in conjunction with Src family
kinases (SFKs), spleen tyrosine kinase (Syk), and phospholipase gamma2
(PLCgamma2). Previous reports have shown that rhodocytin-induced platelet
aggregation depends on secondary mediators such as thromboxane A2 (TxA2) and ADP,
which are agonists for G-protein-coupled receptors (GPCRs) on platelets. How the
secondary mediators regulate CLEC-2-mediated platelet activation in terms of
signaling is not clearly defined. In this study, we report that CLEC-2-induced
Syk and PLCgamma2 phosphorylation is potentiated by TxA2 and that TxA2 plays a
critical role in the most proximal event of CLEC-2 signaling, i.e. the CLEC-2
receptor tyrosine phosphorylation. We show that the activation of other GPCRs,
such as the ADP receptors and protease-activated receptors, can also potentiate
CLEC-2 signaling. By using the specific Gq inhibitor, UBO-QIC, or Gq knock-out
murine platelets, we demonstrate that Gq signaling, but not other G-proteins, is
essential for GPCR-induced potentiation of Syk phosphorylation downstream of CLEC
2. We further elucidated the signaling downstream of Gq and identified an
important role for the PLCbeta-PKCalpha pathway, possibly regulating activation
of SFKs, which are crucial for initiation of CLEC-2 signaling. Together, these
results provide evidence for novel Gq-PLCbeta-PKCalpha-mediated regulation of
proximal CLEC-2 signaling by Gq-coupled receptors.
PMID- 28705935
TI - Forkhead box O3 (FoxO3) regulates kidney tubular autophagy following urinary
tract obstruction.
AB - Autophagy has been shown to be important for normal homeostasis and adaptation to
stress in the kidney. Yet, the molecular mechanisms regulating renal epithelial
autophagy are not fully understood. Here, we explored the role of the stress
responsive transcription factor forkhead box O3 (FoxO3) in mediating injury
induced proximal tubular autophagy in mice with unilateral ureteral obstruction
(UUO). We show that following UUO, FoxO3 is activated and displays nuclear
expression in the hypoxic proximal tubules exhibiting high levels of autophagy.
Activation of FoxO3 by mutating phosphorylation sites to enhance its nuclear
expression induces profound autophagy in cultured renal epithelial cells.
Conversely, deleting FoxO3 in mice results in fewer numbers of autophagic cells
in the proximal tubules and reduced ratio of the autophagy-related protein LC3
II/I in the kidney post-UUO. Interestingly, autophagic cells deficient in FoxO3
contain lower numbers of autophagic vesicles per cell. Analyses of individual
cells treated with autophagic inhibitors to sequentially block the autophagic
flux suggest that FoxO3 stimulates the formation of autophagosomes to increase
autophagic capacity but has no significant effect on autophagosome-lysosome
fusion or autolysosomal clearance. Furthermore, in kidneys with persistent UUO
for 7 days, FoxO3 activation increases the abundance of mRNA and protein levels
of the core autophagy-related (Atg) proteins including Ulk1, Beclin-1, Atg9A,
Atg4B, and Bnip3, suggesting that FoxO3 may function to maintain components of
the autophagic machinery that would otherwise be consumed during prolonged
autophagy. Taken together, our findings indicate that FoxO3 activation can both
induce and maintain autophagic activities in renal epithelial cells in response
to injury from urinary tract obstruction.
PMID- 28705937
TI - HHV8 genotype study in an HIV+ patient with concurrent Kaposi sarcoma and
extracavitary primary effusion lymphoma.
PMID- 28705936
TI - CD14 is a key mediator of both lysophosphatidic acid and lipopolysaccharide
induction of foam cell formation.
AB - Macrophage uptake of oxidized low-density lipoprotein (oxLDL) plays an important
role in foam cell formation and the pathogenesis of atherosclerosis. We report
here that lysophosphatidic acid (LPA) enhances lipopolysaccharide (LPS)-induced
oxLDL uptake in macrophages. Our data revealed that both LPA and LPS highly
induce the CD14 expression at messenger RNA and protein levels in macrophages.
The role of CD14, one component of the LPS receptor cluster, in LPA-induced
biological functions has been unknown. We took several steps to examine the role
of CD14 in LPA signaling pathways. Knockdown of CD14 expression nearly completely
blocked LPA/LPS-induced oxLDL uptake in macrophages, demonstrating for the first
time that CD14 is a key mediator responsible for both LPA- and LPS-induced oxLDL
uptake/foam cell formation. To determine the molecular mechanism mediating CD14
function, we demonstrated that both LPA and LPS significantly induce the
expression of scavenger receptor class A type I (SR-AI), which has been
implicated in lipid uptake process, and depletion of CD14 levels blocked LPA/LPS
induced SR-AI expression. We further showed that the SR-AI-specific antibody,
which quenches SR-AI function, blocked LPA- and LPS-induced foam cell formation.
Thus, SR-AI is the downstream mediator of CD14 in regulating LPA-, LPS-, and
LPA/LPS-induced foam cell formation. Taken together, our results provide the
first experimental evidence that CD14 is a novel connecting molecule linking both
LPA and LPS pathways and is a key mediator responsible for LPA/LPS-induced foam
cell formation. The LPA/LPS-CD14-SR-AI nexus might be the new convergent pathway,
contributing to the worsening of atherosclerosis.
PMID- 28705938
TI - Can enhanced screening of men with a history of prior syphilis infection stem the
epidemic in men who have sex with men? A mathematical modelling study.
AB - OBJECTIVES: The aim of this study is to determine the transmission impact of
using prior syphilis infection to guide a focused syphilis screening intervention
among men who have sex with men (MSM). METHODS: We parameterised a deterministic
model of syphilis transmission in MSM to reflect the 2011-2015 syphilis outbreak
in Winnipeg, Canada. Enhanced screening of 75% of men with prior syphilis every 3
months (A) was compared with distributing equivalent number tests to all MSM (B)
or those with the highest partner number (C). We compared early syphilis
incidence, diagnoses and prevalence after 10 years, relative to a base case of
30% of MSM screened annually. RESULTS: Strategy A was expected to avert 52% of
incident infections, 44% of diagnosed cases and reduce early syphilis prevalence
by 89%. Strategy B had the least impact. Strategy C was most effective, averting
59% of incident cases. When screening frequency was semiannual or annual,
strategy A was the most effective. CONCLUSIONS: Enhanced screening of MSM with
prior syphilis may efficiently reduce transmission, especially when
identification of high-risk men via self-reported partner numbers or high
frequency screening is difficult to achieve.
PMID- 28705939
TI - Changes in pulmonary exercise haemodynamics in scleroderma: a 4-year prospective
study.
AB - Pulmonary arterial hypertension (PAH) is a feared complication of systemic
sclerosis. In this prospective cohort study, we monitored the changes in resting
and exercise pulmonary haemodynamics of scleroderma patients without initial PAH
over a mean follow-up period of ~4 years.All patients underwent exercise
echocardiography and cardiopulmonary exercise testing at baseline and follow-up.
A subgroup underwent exercise right heart catheter (RHC) investigations. The
primary end-point was the echocardiographic systolic pulmonary arterial pressure
at 50 W exercise (sPAP50).We included 99 patients, of whom 58 had a complete
dataset. Three out of 99 patients developed RHC-confirmed PAH (0.75 cases per 100
patient-years). sPAP50 increased (p<0.001) and peak oxygen uptake (secondary end
point) decreased significantly (p=0.001) during follow-up, but there was no
significant change in resting sPAP (p=0.38). In the RHC subgroup (n=28), mean
(m)PAP and pulmonary vascular resistance at 50 W increased significantly (p=0.02
and p=0.002, respectively), but resting mPAP was unchanged.Scleroderma patients
without PAH develop a mild but significant deterioration of pulmonary exercise
haemodynamics and exercise capacity over a 4-year follow-up period, indicating a
progression of pulmonary vascular disease. The manifestation rate of RHC
confirmed PAH was 0.75 cases per 100 patient-years.
PMID- 28705940
TI - Characterisation of eppin function: expression and activity in the lung.
AB - Eppin is a serine protease inhibitor expressed in male reproductive tissues.The
aim of this study was to investigate the localisation and regulation of eppin
expression in myeloid and epithelial cell lines, and explore its potential role
as a multifunctional host defence protein.Using immunohistochemistry and Western
blotting, eppin was detected in the lungs of patients with acute respiratory
distress syndrome and cystic fibrosis lung disease. Expression of eppin in
monocytic cells was unaffected by stimulation with Toll-like receptor agonists,
cytokines and hormone receptor agonists. However, upregulated expression and
secretion of eppin was observed following treatment of monocytes with epidermal
growth factor. Incubation of recombinant eppin with monocytic cells resulted in
significant inhibition of lipopolysaccharide-induced chemokine production.
Furthermore, eppin inhibited lipopolysaccharide-induced NF-kappaB activation by a
mechanism which involved accumulation of phosphorylated IkappaBalpha. In an in
vivo model of lung inflammation induced by lipopolysaccharide, eppin
administration resulted in decreased recruitment of neutrophils to the lung with
a concomitant reduction in the levels of the neutrophil chemokine macrophage
inflammatory protein-2.Overall, these results suggest a role for eppin outside of
the reproductive tract and that eppin may have a role in the innate immune
response in the lung.
PMID- 28705941
TI - Tyk2 as a target for immune regulation in human viral/bacterial pneumonia.
AB - The severity and lethality of influenza A virus (IAV) infections is frequently
aggravated by secondary bacterial pneumonia. However, the mechanisms in human
lung tissue that provoke this increase in fatality are unknown and therapeutic
immune modulatory options are lacking.We established a human lung ex vivo co
infection model to investigate innate immune related mechanisms contributing to
the susceptibility of secondary pneumococcal pneumonia.We revealed that type I
and III interferon (IFN) inhibits Streptococcus pneumoniae-induced interleukin
(IL)-1beta release. The lack of IL-1beta resulted in the repression of
bacterially induced granulocyte-macrophage colony-stimulating factor (GM-CSF)
liberation. Specific inhibition of IFN receptor I and III-associated tyrosine
kinase 2 (Tyk2) completely restored the S. pneumoniae-induced IL-1beta-GM-CSF
axis, leading to a reduction of bacterial growth. A preceding IAV infection of
the human alveolus leads to a type I and III IFN-dependent blockade of the early
cytokines IL-1beta and GM-CSF, which are key for orchestrating an adequate innate
immune response against bacteria. Their virally induced suppression may result in
impaired bacterial clearance and alveolar repair.Pharmacological inhibition of
Tyk2 might be a new treatment option to sustain beneficial endogenous GM-CSF
levels in IAV-associated secondary bacterial pneumonia.
PMID- 28705942
TI - Mycobacterium abscessus in patients with cystic fibrosis: low impact of inter
human transmission in Italy.
PMID- 28705943
TI - "Long-term volume-targeted pressure-controlled ventilation: sense or nonsense?"
Maria Paola Arellano-Maric, Cesare Gregoretti, Marieke Duiverman and Wolfram
Windisch. Eur Respir J 2017; 49: 1602193.
PMID- 28705944
TI - Resistive or dynamic exercise stress testing of the pulmonary circulation and the
right heart.
PMID- 28705945
TI - Alcohol consumption as a risk factor for tuberculosis: meta-analyses and burden
of disease.
AB - Meta-analyses of alcohol use, alcohol dosage and alcohol-related problems as risk
factors for tuberculosis incidence were undertaken. The global alcohol
attributable tuberculosis burden of disease was also re-estimated.Systematic
searches were conducted, reference lists were reviewed and expert consultations
were held to identify studies. Cohort and case-control studies were included if
there were no temporal violations of exposure and outcome. Risk relations (RRs)
were pooled by using categorical and dose-response meta-analyses. The alcohol
attributable tuberculosis burden of disease was estimated by using alcohol
attributable fractions.36 of 1108 studies were included. RRs for alcohol use and
alcohol-related problems were 1.35 (95% CI 1.09-1.68; I2: 83%) and 3.33 (95% CI
2.14-5.19; 87%), respectively. Concerning alcohol dosage, tuberculosis risk rose
as ethanol intake increased, with evidence of a threshold effect. Alcohol
consumption caused 22.02 incident cases (95% CI 19.70-40.77) and 2.35 deaths (95%
CI 2.05-4.79) per 100 000 people from tuberculosis in 2014. Alcohol-attributable
tuberculosis incidence increased between 2000 and 2014 in most high tuberculosis
burden countries, whereas mortality decreased.Alcohol consumption was associated
with an increased risk of tuberculosis in all meta-analyses. It was consequently
a major contributor to the tuberculosis burden of disease.
PMID- 28705946
TI - Unmasking hidden disease: exercise pulmonary haemodynamics in systemic sclerosis.
PMID- 28705947
TI - Targeting harmful use of alcohol for prevention and treatment of tuberculosis: a
call for action.
PMID- 28705948
TI - Taken to task: what is and is not an appropriate response to an ERS guidelines
task force?
PMID- 28705949
TI - Computer-aided reading of tuberculosis chest radiography: moving the research
agenda forward to inform policy.
PMID- 28705950
TI - Survival in multiple sclerosis: things have changed.
PMID- 28705951
TI - Excess mortality among patients with multiple sclerosis in Denmark has dropped
significantly over the past six decades: a population based study.
AB - BACKGROUND: Lifetime expectancy in multiple sclerosis (MS) is reduced. Few
studies have had sufficient follow-up or sufficient number of patients to assess
if survival has improved with time. However, a recent meta-analysis found no time
dependent change in MS excess mortality across studies over recent decades.
OBJECTIVE: To investigate whether short-term all-cause excess mortality in
patients with MS in the total Danish population has changed over the last six
decades. PATIENTS AND METHODS: We included all patients with MS recorded in the
nationwide Danish MS Registry with definite or probable MS and onset from 1950
through 1999. The Danish Civil Registration System provided date of death for all
deceased patients with follow-up in 2015, and Statistics Denmark supplied
specific population mortality. We calculated excess number of death per 1000
person-years (EDR) and standardised mortality ratio (SMR). RESULTS: We included
18 847 patients among whom 6102 had died as opposed to 2492 expected deaths. EDR
was 10.63 (95% CI 10.19 to 11.09) and a SMR was 2.45 (95% CI 2.39 to 2.51). The
15-year EDR dropped gradually from 11.29 (95% CI 9.95 to 12.73) in the 1950-1959
onset cohort to 2.56 (95% CI 1.98 to 3.18) in the 1990-1999 onset cohort, and SMR
dropped from 4.48 (95% CI 4.06 to 4.92) to 1.80 (95% CI 1.62 to 1.99).
CONCLUSION: The decline in short-term excess mortality in MS started decades
before disease-modifying treatment of MS became available, before use of MRI
became widespread, and before the McDonald diagnostic criteria were introduced. A
change in the MS cohorts with fewer malignant cases may be a significant
contributor.
PMID- 28705952
TI - Hypoglossal myokymia presenting as paroxysmal dysarthria following head and neck
radiotherapy.
PMID- 28705953
TI - MicroRNAs in the skin: role in development, homoeostasis and regeneration.
AB - The skin is the largest organ of the integumentary system and possesses a vast
number of functions. Due to the distinct layers of the skin and the variety of
cells which populate each, a tightly regulated network of molecular signals
control development and regeneration, whether due to programmed cell termination
or injury. MicroRNAs (miRs) are a relatively recent discovery; they are a class
of small non-coding RNAs which possess a multitude of biological functions due to
their ability to regulate gene expression via post-transcriptional gene
silencing. Of interest, is that a plethora of data demonstrates that a number of
miRs are highly expressed within the skin, and are evidently key regulators of
numerous vital processes to maintain non-aberrant functioning. Recently, miRs
have been targeted as therapeutic interventions due to the ability of synthetic
'antagomiRs' to down-regulate abnormal miR expression, thereby potentiating wound
healing and attenuating fibrotic processes which can contribute to disease such
as systemic sclerosis (SSc). This review will provide an introduction to the
structure and function of the skin and miR biogenesis, before summarizing the
literature pertaining to the role of miRs. Finally, miR therapies will also be
discussed, highlighting important future areas of research.
PMID- 28705954
TI - Spending on public health cut as councils look to save money.
PMID- 28705955
TI - Tracking the Bacterial Type III Secretion System: Visualization of Effector
Delivery Using Split Fluorescent Proteins.
PMID- 28705957
TI - Complete Genome Sequence of Streptococcus pneumoniae Virulent Phage MS1.
AB - The lytic Streptococcus pneumoniae phage MS1 was isolated from a throat swab of a
patient with symptoms of upper respiratory tract infection. The genome of this
siphophage has 56,075 bp, 42.3% G+C content, and 77 open reading frames,
including queuosine biosynthesis genes. Phage MS1 is related to pneumococcal
phage Dp-1.
PMID- 28705958
TI - First Genome Sequences of Dengue Virus (DENV) Strains Isolated during the First
DENV-4 Outbreak in Sao Paulo, Brazil.
AB - Dengue virus (DENV) is an arbovirus belonging to the genus Flavivirus, family
Flaviviridae In Brazil, the reemergence and spread of DENV type 4 (DENV-4) across
the country were responsible for a significant outbreak in Guaruja, Sao Paulo,
Brazil. Here, we report the first genomic sequences of DENV strains circulating
in Guaruja during the 2013 outbreak.
PMID- 28705959
TI - Draft Genome Sequences of 256 Salmonella enterica subsp. enterica Serovar
Enteritidis Strains Isolated from Humans, Food, Chickens, and Farm Environments
in Brazil.
AB - Salmonella enterica subsp. enterica serovar Enteritidis emerged in the late 1980s
as the most isolated Salmonella serovar worldwide. Here, we report the draft
genomes of 256 S Enteritidis strains isolated from humans, food, chickens, and
farm environments in Brazil. These draft genomes will help enhance our
understanding of this serovar in Brazil.
PMID- 28705956
TI - Rapid Recovery Gene Downregulation during Excess-Light Stress and Recovery in
Arabidopsis.
AB - Stress recovery may prove to be a promising approach to increase plant
performance and, theoretically, mRNA instability may facilitate faster recovery.
Transcriptome (RNA-seq, qPCR, sRNA-seq, and PARE) and methylome profiling during
repeated excess-light stress and recovery was performed at intervals as short as
3 min. We demonstrate that 87% of the stress-upregulated mRNAs analyzed exhibit
very rapid recovery. For instance, HSP101 abundance declined 2-fold every 5.1
min. We term this phenomenon rapid recovery gene downregulation (RRGD), whereby
mRNA abundance rapidly decreases promoting transcriptome resetting. Decay
constants (k) were modeled using two strategies, linear and nonlinear least
squares regressions, with the latter accounting for both transcription and
degradation. This revealed extremely short half-lives ranging from 2.7 to 60.0
min for 222 genes. Ribosome footprinting using degradome data demonstrated RRGD
loci undergo cotranslational decay and identified changes in the ribosome
stalling index during stress and recovery. However, small RNAs and 5'-3' RNA
decay were not essential for recovery of the transcripts examined, nor were any
of the six excess light-associated methylome changes. We observed recovery
specific gene expression networks upon return to favorable conditions and six
transcriptional memory types. In summary, rapid transcriptome resetting is
reported in the context of active recovery and cellular memory.
PMID- 28705960
TI - Draft Whole-Genome Assemblies of Drug-Resistant Clinical Isolates of Klebsiella
pneumoniae from the Philippines.
AB - Here, we report the draft assemblies of 11 clinical isolates of Klebsiella
pneumoniae that are resistant to cephalosporins, carbapenems, and/or colistin.
The assemblies ranged from 5.37 Mbp to 5.70 Mbp in size. Several plasmid
sequences were present, and resistance genes spanning multiple classes of
antibiotics were predicted.
PMID- 28705961
TI - Draft Genome Sequence of Bacteriophage vB_Eco_swan01.
AB - Bacteriophage vB_Eco_swan01 was isolated from an ornamental pool using
Escherichia coli MG1655 as the host. Bacteriophage vB_Eco_swan01 has limited
similarity with other known phages at the nucleotide level and likely represents
a new bacteriophage species within the Tunavirinae.
PMID- 28705962
TI - Genome Sequences of Five Streptomyces Bacteriophages Forming Cluster BG.
AB - Cluster BG of the actinobacteriophage was formed upon discovery of five novel
bacteriophages isolated by enrichment from their host, Streptomyces griseus
subsp. griseus strain ATCC 10137. Four members of this cluster (BabyGotBac, Maih,
TP1605, and YDN12) share over 89% average nucleotide identity, while the other
(Xkcd426) has only 72% similarity to other cluster members.
PMID- 28705963
TI - Draft Genome Sequences of 1,183 Salmonella Strains from the 100K Pathogen Genome
Project.
AB - Salmonella is a common food-associated bacterium that has substantial impact on
worldwide human health and the global economy. This is the public release of
1,183 Salmonella draft genome sequences as part of the 100K Pathogen Genome
Project. These isolates represent global genomic diversity in the Salmonella
genus.
PMID- 28705964
TI - Draft Genome Sequences of Seven Streptococcus agalactiae Strains Isolated from
Camelus dromedarius at the Horn of Africa.
AB - We present draft whole-genome sequences of seven Streptococcus agalactiae strains
isolated from Camelus dromedarius in Kenya and Somalia. These data are an
extension to the group B Streptococcus (GBS) pangenome and might provide more
insight into the underlying mechanisms of pathogenicity and antibiotic resistance
of camel GBS.
PMID- 28705965
TI - Draft Genome Sequences of Three Actinobacteria Strains Presenting New Candidate
Organisms with High Potentials for Specific P450 Cytochromes.
AB - The three Actinobacteria strains Streptomyces platensis DSM 40041, Pseudonocardia
autotrophica DSM 535, and Streptomyces fradiae DSM 40063 were described to
selectively oxyfunctionalize several drugs. Here, we present their draft genomes
to unravel their gene sets encoding promising cytochrome P450 monooxygenases
associated with the generation of drug metabolites.
PMID- 28705966
TI - Genome Sequence of Oxalobacter formigenes Strain OXCC13.
AB - The lack of Oxalobacter formigenes colonization in the human gut is generally
acknowledged as a risk factor for kidney stone formation since this microorganism
can play an important role in oxalate homeostasis. Here, we present the genome
sequence of OXCC13, a human strain isolated from an individual residing in
Germany.
PMID- 28705967
TI - Genome Sequence of Mycobacterium Phage CrystalP.
AB - Mycobacteriophage CrystalP is a newly isolated phage infecting Mycobacterium
smegmatis strain mc2155. CrystalP has a 76,483-bp genome and is predicted to
contain 143 protein-coding and 2 tRNA genes, including repressor and integrase
genes consistent with a temperate lifestyle. CrystalP is related to the
mycobacteriophages Toto and Kostya and to other Cluster E phages.
PMID- 28705968
TI - Genome Sequence of Micromonospora sp. NBS 11-29, an Antibiotic and Hydrolytic
Enzyme Producer, Isolated from River Sediment in Brazil.
AB - The genus Micromonospora comprises actinomycetes with high biotechnological
potential, due to their ability to produce secondary metabolites and enzymes. In
this study, we report the draft genome sequence of Micromonospora sp. NBS 11-29,
which showed antibacterial, cellulolytic, and xylanolytic activities under in
vitro conditions.
PMID- 28705969
TI - First Draft Genome for a Burkholderia mallei Isolate Originating from a
Glanderous Mule from Brazil.
AB - Burkholderia mallei is the etiological agent of glanders. Here, we present the
draft genome sequence of Burkholderia mallei strain 16-2438_BM#8 that was
isolated from a mule found dead in Pernambuco, northeast Brazil. It is the first
available genomic sequence from a strain isolated on the American continent.
PMID- 28705970
TI - De Novo Whole-Genome Sequencing of the Wood Rot Fungus Polyporus brumalis, Which
Exhibits Potential Terpenoid Metabolism.
AB - Polyporus brumalis is able to synthesize several sesquiterpenes during fungal
growth. Using a single-molecule real-time sequencing platform, we present the 53
Mb draft genome of P. brumalis, which contains 6,231 protein-coding genes. Gene
annotation and isolation support genetic information, which can increase the
understanding of sesquiterpene metabolism in P. brumalis.
PMID- 28705971
TI - 100K Pathogen Genome Project.
AB - The 100K Pathogen Genome Project is producing draft and closed genome sequences
from diverse pathogens. This project expanded globally to include a snapshot of
global bacterial genome diversity. The genomes form a sequence database that has
a variety of uses from systematics to public health.
PMID- 28705972
TI - Whole-Genome Sequences of Influenza A(H1N1)pdm09 Virus Isolates from Kerala,
India.
AB - We report here the whole-genome sequence of six clinical isolates of influenza
A(H1N1)pdm09, isolated from Kerala, India. Amino acid analysis of all gene
segments from the A(H1N1)pdm09 isolates obtained in 2014 and 2015 identified
several new mutations compared to the 2009 A(H1N1) pandemic strain.
PMID- 28705973
TI - Complete Genome Sequences of Three Xanthomonas citri Strains from Texas.
AB - The complete genome sequences of three Xanthomonas citri strains isolated from
lime trees in Texas were found to belong to the Aw group. All carried nearly
identical large plasmids with similarity to those of a citrus canker strain from
India and to xanthomonads from Africa and Colombia. All three strains harbored
unusual pthA homologs.
PMID- 28705974
TI - Draft Genome Sequence of Klebsiella michiganensis 3T412C, Harboring an Arsenic
Resistance Genomic Island, Isolated from Mine Tailings in Peru.
AB - An arsenic resistance genomic island in the bacterium Klebsiella michiganensis
3T412C was isolated from mine tailings from Peru. This genomic island confers
adaptation to extreme environments with high concentrations of arsenic. Isolate
3T412C contained a complete set of genes involved in resistance to arsenic. This
operon is surrounded by putative genes for resistance to other heavy metals.
PMID- 28705975
TI - Draft Genome Sequence of Plasmodium gonderi, a Malaria Parasite of African Old
World Monkeys.
AB - Plasmodium gonderi is a primate parasite whose natural host is the African Old
World monkeys. Here, we report the draft genome sequence for P. gonderi The data
are useful not only for understanding the evolution of malaria but also for
allowing the comparative genomics of malaria parasites.
PMID- 28705976
TI - Genome Sequences of New Faustovirus Strains ST1 and LC9, Isolated from the South
of France.
AB - Faustoviruses are amoeba-infecting giant viruses closely related to the
Asfarviridae family. Here, we report the isolation, genome sequencing, and
annotation of ST1 and LC9, two new strains belonging to lineages L and E9 of
faustoviruses, currently represented by only one representative each.
PMID- 28705977
TI - Draft Genome Sequences of Two Mycobacterium bovis Strains Isolated from Beef
Cattle in Paraguay.
AB - This work reports the draft genome sequences of the Mycobacterium bovis strains
M1009 and M1010, isolated from the lymph nodes of two infected cows on a beef
farm in Paraguay. Comparative genomics between these strains and other regional
strains may provide more insights regarding M. bovis epidemiology in South
America.
PMID- 28705978
TI - Draft Genome Sequences of Pseudoalteromonas tetraodonis CSB01KR and
Pseudoalteromonas lipolytica CSB02KR, Isolated from the Gut of the Sea Cucumber
Apostichopus japonicus.
AB - We present here the complete genome sequences of two newly isolated
Pseudoalteromonas tetraodonis and Pseudoalteromonas lipolytica strains, isolated
from the gut of the sea cucumber Apostichopus japonicus, to provide a useful
means for facilitating the study of antibacterial, bacteriolytic, agarolytic, and
algicidal activities of marine Pseudoalteromonas species.
PMID- 28705979
TI - Draft Genome Sequence of Bacillus altitudinis YNP4-TSU, Isolated from Yellowstone
National Park.
AB - Undisturbed hot springs inside Yellowstone National Park remain a dynamic biome
for novel cellulolytic thermophiles. We report here the draft genome sequence of
one of these isolates, Bacillus altitudinis YNP4-TSU.
PMID- 28705980
TI - Complete Genome Sequences of Lactococcus lactis subsp. lactis bv. diacetylactis
FM03 and Leuconostoc mesenteroides FM06 Isolated from Cheese.
AB - Here, the genome sequences of Lactococcus lactis subsp. lactis bv. diacetylactis
FM03 and Leuconostoc mesenteroides FM06, both isolated from cheese, are
presented. FM03 and FM06 contain 7 and 3 plasmids, respectively, that carry genes
encoding functions important for growth and survival in dairy fermentations.
PMID- 28705981
TI - High-Quality Draft Genome Sequence of Lactobacillus casei Strain Z11, Isolated
from a Human Adult Intestinal Biopsy Sample.
AB - Several Lactobacillus casei strains are used as probiotics. L. casei strain Z11,
isolated from a human colon biopsy sample, has been suggested as a probiotic
candidate based on promising properties in vitro Here, we present a 2.74-Mbp high
quality draft genome sequence for this strain.
PMID- 28705982
TI - Draft Genome Sequence of Alkalinema sp. Strain CACIAM 70d, a Cyanobacterium
Isolated from an Amazonian Freshwater Environment.
AB - In order to increase the genomic data of cyanobacterial strains isolated in
Brazil, we hereby present the draft genome sequence of the Alkalinema sp. strain
CACIAM 70d, isolated from an Amazonian freshwater environment. This report
describes the first genome available for this genus.
PMID- 28705983
TI - Completed Genome Sequences of Borrelia burgdorferi Sensu Stricto B31(NRZ) and
Closely Related Patient Isolates from Europe.
AB - Borrelia burgdorferi sensu stricto is a causative agent of human Lyme borreliosis
in the United States and Europe. We report here the completed genome sequences of
strain B31 isolated from a tick in the United States and two closely related
strains from Europe, PAli and PAbe, which were isolated from patients with
erythema migrans and neuroborreliosis, respectively.
PMID- 28705984
TI - Draft Genome Sequence of Eggerthia catenaformis Strain MAR1 Isolated from Saliva
of Healthy Humans.
AB - Here, we report the draft genome sequence of Eggerthia catenaformis MAR1 isolated
during a screen for d-cycloserine-resistant bacteria from the saliva of healthy
humans. Analysis of the genome reveals that the strain has the potential to be a
human pathogen and carries genes related to virulence and antibiotic resistance.
PMID- 28705985
TI - De Novo Whole-Genome Sequence of Pantoea latae Strain AS1, Isolated from Zamia
floridana Rhizosphere in Central Florida, USA.
AB - Pantoea latae strain AS1 was isolated from the rhizophere of a cycad, Zamia
floridana, in central Florida, USA. Here, we report the de novo whole-genome
sequence of this strain, which consists of a total of 83 contigs spanning
4,960,415 bp, with a G+C content of 59.6%, and comprising 4,527 predicted coding
sequences.
PMID- 28705986
TI - Draft Genome Sequence of Multidrug-Resistant Cellulosimicrobium sp. Strain KWT-B,
Isolated from Feces of Hirundo rustica.
AB - Migratory birds have been postulated as potential spreaders of antibiotic
resistance. Multidrug-resistant Cellulosimicrobium sp. strain KWT-B was isolated
from the feces of Hirundo rustica A draft genome sequence indicated that the
strain harbors multidrug-resistant transporters, multidrug efflux pumps, a
vancomycin-resistant protein, and metallo-beta-lactamases.
PMID- 28705987
TI - East not least for Pacific bluefin tuna.
PMID- 28705988
TI - Large-amplitude transfer motion of hydrated excess protons mapped by ultrafast 2D
IR spectroscopy.
AB - Solvation and transport of excess protons in aqueous systems play a fundamental
role in acid-base chemistry and biochemical processes. We mapped ultrafast proton
excursions along the proton transfer coordinate by means of two-dimensional
infrared spectroscopy, both in bulk water and in a Zundel cation (H5O2)+ motif
selectively prepared in acetonitrile. Electric fields from the environment and
stochastic hydrogen bond motions induce fluctuations of the proton double-minimum
potential. Within the lifetime of a particular hydration geometry, the proton
explores a multitude of positions on a sub-100-femtosecond time scale. The proton
transfer vibration is strongly damped by its 20- to 40-femtosecond population
decay. Our results suggest a central role of Zundel-like geometries in aqueous
proton solvation and transport.
PMID- 28705989
TI - Emergent cellular self-organization and mechanosensation initiate follicle
pattern in the avian skin.
AB - The spacing of hair in mammals and feathers in birds is one of the most apparent
morphological features of the skin. This pattern arises when uniform fields of
progenitor cells diversify their molecular fate while adopting higher-order
structure. Using the nascent skin of the developing chicken embryo as a model
system, we find that morphological and molecular symmetries are simultaneously
broken by an emergent process of cellular self-organization. The key initiators
of heterogeneity are dermal progenitors, which spontaneously aggregate through
contractility-driven cellular pulling. Concurrently, this dermal cell aggregation
triggers the mechanosensitive activation of beta-catenin in adjacent epidermal
cells, initiating the follicle gene expression program. Taken together, this
mechanism provides a means of integrating mechanical and molecular perspectives
of organ formation.
PMID- 28705990
TI - Systemic pan-AMPK activator MK-8722 improves glucose homeostasis but induces
cardiac hypertrophy.
AB - 5'-Adenosine monophosphate-activated protein kinase (AMPK) is a master regulator
of energy homeostasis in eukaryotes. Despite three decades of investigation, the
biological roles of AMPK and its potential as a drug target remain incompletely
understood, largely because of a lack of optimized pharmacological tools. We
developed MK-8722, a potent, direct, allosteric activator of all 12 mammalian
AMPK complexes. In rodents and rhesus monkeys, MK-8722-mediated AMPK activation
in skeletal muscle induced robust, durable, insulin-independent glucose uptake
and glycogen synthesis, with resultant improvements in glycemia and no evidence
of hypoglycemia. These effects translated across species, including diabetic
rhesus monkeys, but manifested with concomitant cardiac hypertrophy and increased
cardiac glycogen without apparent functional sequelae.
PMID- 28705992
TI - Beyond just hemoglobin: Red blood cell potentiation of hemoglobin-oxygen
unloading in fish.
AB - Teleosts comprise 95% of fish species, almost one-half of all vertebrate species,
and represent one of the most successful adaptive radiation events among
vertebrates. This is thought to be in part because of their unique oxygen (O2)
transport system. In salmonids, recent in vitro and in vivo studies indicate that
hemoglobin-oxygen (Hb-O2) unloading to tissues may be doubled or even tripled
under some conditions without changes in perfusion. This is accomplished through
the short circuiting of red blood cell (RBC) pH regulation, resulting in a large
arterial-venous pH difference within the RBC and induced reduction in Hb-O2
affinity. This system has three prerequisites: 1) highly pH-sensitive hemoglobin,
2) rapid RBC pH regulation, and 3) a heterogeneous distribution of plasma
accessible CA in the cardiovascular system (presence in the tissues and absence
at the gills). Although data are limited, these attributes may be general
characteristics of teleosts. Although this system is not likely operational to
the same degree in other vertebrates, some of these prerequisites do exist, and
the generation and elimination of pH disequilibrium states at the RBC will likely
enhance Hb-O2 unloading to some degree. In human disease states, there are
conditions that may partly satisfy those for enhanced Hb-O2 unloading,
tentatively an avenue for future work that may improve treatment efficacy.
PMID- 28705991
TI - Oxygen metabolism and innate immune responses in the gut.
AB - Epithelial cells of the mucosa provide a first line of defense to prevent the
inappropriate translocation of luminal antigens, and therefore contribute
significantly to nonspecific innate immunity. In the gastrointestinal (GI) tract,
barrier is provided by multiple components of the mucosa, including mucus
production, epithelial junctional complexes, and the production of antimicrobial
molecules. In recent years, it is better appreciated that tissue oxygen
metabolism is key to homeostasis in the mucosa. The intestine, for example,
maintains a low baseline Po2 level due to high rates of metabolism,
countercurrent blood flow, and the presence of a steep oxygen gradient across the
luminal aspect of tissue surface. As a result, hypoxia and hypoxia-inducible
factor (HIF)-dependent signaling exists even in the healthy, unperturbed
intestinal mucosa. In a number of examples, HIF has been demonstrated both to
promote barrier function during homeostasis and to promote resolution of active
inflammation. Hypoxia-elicited factors that contribute to innate responses in the
mucosa include the transcriptional regulation of mucin genes, junction proteins,
and autophagic flux. Here, we review current literature related to hypoxia and
innate immunity in health and during mucosal inflammation.
PMID- 28705993
TI - Effects of beta-hydroxy-beta-methylbutyrate on skeletal muscle mitochondrial
content and dynamics, and lipids after 10 days of bed rest in older adults.
AB - Loss of muscle mass during periods of disuse likely has negative health
consequences for older adults. We have previously shown that beta-hydroxy-beta
methylbutyrate (HMB) supplementation during 10 days of strict bed rest (BR)
attenuates the loss of lean mass in older adults. To elucidate potential
molecular mechanisms of HMB effects on muscle during BR and resistance training
rehabilitation (RT), we examined mediators of skeletal muscle mitochondrial
dynamics, autophagy and atrophy, and intramyocellular lipids. Nineteen older
adults (60-76 yr) completed 10 days BR followed by 8-wk RT rehabilitation.
Subjects were randomized to either HMB (3 g/day HMB; n = 11) or control (CON; n =
8) groups. Skeletal muscle cross-sectional area (CSA) was determined by histology
from percutaneous vastus lateralis biopsies. We measured protein markers of
mitochondrial content [oxidative phosphorylation (OXPHOS)], fusion and fission
(MFN2, OPA1, FIS1, and DRP1), autophagy (Beclin1, LC3B, and BNIP3), and atrophy
[poly-ubiquinated proteins (poly-ub)] by Western blot. Fatty acid composition of
several lipid classes in skeletal muscle was measured by infusion-MS analysis.
Poly-ub proteins and OXPHOS complex I increased in both groups following BR (P <
0.05, main effect for time), and muscle triglyceride content tended to increase
following BR in the HMB group (P = 0.055). RT rehabilitation increased OXPHOS
complex II protein (P < 0.05), and total OXPHOS content tended (P = 0.0504) to be
higher in HMB group. In addition, higher levels of DRP1 and MFN2 were maintained
in the HMB group after RT (P < 0.05). BNIP3 and poly-ub proteins were
significantly reduced following rehabilitation in both groups (P < 0.05).
Collectively, these data suggest that HMB influences mitochondrial dynamics and
lipid metabolism during disuse atrophy and rehabilitation.NEW & NOTEWORTHY
Mitochondrial content and dynamics remained unchanged over 10 days of BR in older
adults. HMB stimulated intramuscular lipid storage as triacylglycerol following
10 days of bed rest (BR) and maintained higher mitochondrial OXPHOS content and
dynamics during the 8-wk resistance exercise rehabilitation program.
PMID- 28705994
TI - Wearable brain imaging with multimodal physiological monitoring.
AB - The brain is a central component of cognitive and physical human performance.
Measures, including functional brain activation, cerebral perfusion, cerebral
oxygenation, evoked electrical responses, and resting hemodynamic and electrical
activity are all related to, or can predict, health status or performance
decrements. However, measuring brain physiology typically requires large,
stationary machines that are not suitable for mobile or self-monitoring.
Moreover, when individuals are ambulatory, systemic physiological fluctuations
e.g., in heart rate, blood pressure, skin perfusion, and more-can interfere with
noninvasive brain measurements. In efforts to address the physiological
monitoring and performance assessment needs for astronauts during spaceflight, we
have developed easy-to-use, wearable prototypes, such as NINscan, for near
infrared scanning, which can collect synchronized multimodal physiology data,
including hemodynamic deep-tissue imaging (including brain and muscles),
electroencephalography, electrocardiography, electromyography,
electrooculography, accelerometry, gyroscopy, pressure, respiration, and
temperature measurements. Given their self-contained and portable nature, these
devices can be deployed in a much broader range of settings-including austere
environments-thereby, enabling a wider range of novel medical and research
physiology applications. We review these, including high-altitude assessments,
self-deployable multimodal e.g., (polysomnographic) recordings in remote or low
resource environments, fluid shifts in variable-gravity, or spaceflight analog
environments, intracranial brain motion during high-impact sports, and long
duration monitoring for clinical symptom-capture in various clinical conditions.
In addition to further enhancing sensitivity and miniaturization, advanced
computational algorithms could help support real-time feedback and alerts
regarding performance and health.
PMID- 28705995
TI - Reproducibility of airway luminal size in asthma measured by HRCT.
AB - Brown RH, Henderson RJ, Sugar EA, Holbrook JT, Wise RA, on behalf of the American
Lung Association Airways Clinical Research Centers. Reproducibility of airway
luminal size in asthma measured by HRCT. J Appl Physiol 123: 876-883, 2017. First
published July 13, 2017; doi:10.1152/japplphysiol.00307.2017.-High-resolution CT
(HRCT) is a well-established imaging technology used to measure lung and airway
morphology in vivo. However, there is a surprising lack of studies examining HRCT
reproducibility. The CPAP Trial was a multicenter, randomized, three-parallel
arm, sham-controlled 12-wk clinical trial to assess the use of a nocturnal
continuous positive airway pressure (CPAP) device on airway reactivity to
methacholine. The lack of a treatment effect of CPAP on clinical or HRCT measures
provided an opportunity for the current analysis. We assessed the reproducibility
of HRCT imaging over 12 wk. Intraclass correlation coefficients (ICCs) were
calculated for individual airway segments, individual lung lobes, both lungs, and
air trapping. The ICC [95% confidence interval (CI)] for airway luminal size at
total lung capacity ranged from 0.95 (0.91, 0.97) to 0.47 (0.27, 0.69). The ICC
(95% CI) for airway luminal size at functional residual capacity ranged from 0.91
(0.85, 0.95) to 0.32 (0.11, 0.65). The ICC measurements for airway distensibility
index and wall thickness were lower, ranging from poor (0.08) to moderate (0.63)
agreement. The ICC for air trapping at functional residual capacity was 0.89
(0.81, 0.94) and varied only modestly by lobe from 0.76 (0.61, 0.87) to 0.95
(0.92, 0.97). In stable well-controlled asthmatic subjects, it is possible to
reproducibly image unstimulated airway luminal areas over time, by region, and by
size at total lung capacity throughout the lungs. Therefore, any changes in
luminal size on repeat CT imaging are more likely due to changes in disease state
and less likely due to normal variability.NEW & NOTEWORTHY There is a surprising
lack of studies examining the reproducibility of high-resolution CT in asthma.
The current study examined reproducibility of airway measurements. In stable well
controlled asthmatic subjects, it is possible to reproducibly image airway
luminal areas over time, by region, and by size at total lung capacity throughout
the lungs. Therefore, any changes in luminal size on repeat CT imaging are more
likely due to changes in disease state and less likely due to normal variability.
PMID- 28705996
TI - Different gene response to mechanical loading during early and late phases of rat
Achilles tendon healing.
AB - Mechanical loading stimulates tendon healing both when applied in the
inflammatory phase and in the early remodeling phase of the process, although not
necessarily via the same mechanisms. We investigated the gene response to
mechanical loading in these two phases of tendon healing. The right Achilles
tendon in rats was transected, and the hindlimbs were unloaded by tail
suspension. The rats were exposed to 5 min of treadmill running 3 or 14 days
after tendon transection. Thereafter, they were resuspended for 15 min or 3 h
until euthanasia. The controls were suspended continuously. Gene analysis was
first performed by microarray analysis followed by quantitative RT-PCR on
selected genes, focusing on inflammation. Fifteen minutes after loading, the most
important genes seemed to be the transcription factors EGR1 and C-FOS, regardless
of healing phase. These transcription factors might promote tendon cell
proliferation and differentiation, stimulate collagen production, and regulate
inflammation. Three hours after loading on day 3, inflammation was strongly
affected. Seven inflammation-related genes were upregulated according to PCR:
CCL20, CCL7, IL-6, NFIL3, PTX3, SOCS1, and TLR2. These genes can be connected to
macrophages, T cells, and recruitment of leukocytes. According to Ingenuity
Pathway Analysis, the recruitment of leukocytes was increased by loading on day
3, which also was confirmed by histology. This inflammation-related gene response
was not seen on day 14 Our results suggest that the immediate gene response after
mechanical loading is similar in the early and late phases of healing but the
late gene response is different.NEW & NOTEWORTHY This study investigates the
direct effect of mechanical loading on gene expression during different healing
phases in tendon healing. One isolated episode of mechanical loading was studied
in otherwise unloaded healing tendons. This enabled us to study a time sequence,
i.e., which genes were the first ones to be regulated after the loading episode.
PMID- 28705997
TI - Evidence from high-altitude acclimatization for an integrated cerebrovascular and
ventilatory hypercapnic response but different responses to hypoxia.
AB - Ventilation and cerebral blood flow (CBF) are both sensitive to hypoxia and
hypercapnia. To compare chemosensitivity in these two systems, we made
simultaneous measurements of ventilatory and cerebrovascular responses to hypoxia
and hypercapnia in 35 normal human subjects before and after acclimatization to
hypoxia. Ventilation and CBF were measured during stepwise changes in isocapnic
hypoxia and iso-oxic hypercapnia. We used MRI to quantify actual cerebral
perfusion. Measurements were repeated after 2 days of acclimatization to hypoxia
at 3,800 m altitude (partial pressure of inspired O2 = 90 Torr) to compare
plasticity in the chemosensitivity of these two systems. Potential effects of
hypoxic and hypercapnic responses on acute mountain sickness (AMS) were assessed
also. The pattern of CBF and ventilatory responses to hypercapnia were almost
identical. CO2 responses were augmented to a similar degree in both systems by
concomitant acute hypoxia or acclimatization to sustained hypoxia. Conversely,
the pattern of CBF and ventilatory responses to hypoxia were markedly different.
Ventilation showed the well-known increase with acute hypoxia and a progressive
decline in absolute value over 25 min of sustained hypoxia. With acclimatization
to hypoxia for 2 days, the absolute values of ventilation and O2 sensitivity
increased. By contrast, O2 sensitivity of CBF or its absolute value did not
change during sustained hypoxia for up to 2 days. The results suggest a common or
integrated control mechanism for CBF and ventilation by CO2 but different
mechanisms of O2 sensitivity and plasticity between the systems. Ventilatory and
cerebrovascular responses were the same for all subjects irrespective of AMS
symptoms. NEW & NOTEWORTHY Ventilatory and cerebrovascular hypercapnic response
patterns show similar plasticity in CO2 sensitivity following hypoxic
acclimatization, suggesting an integrated control mechanism. Conversely,
ventilatory and cerebrovascular hypoxic responses differ. Ventilation initially
increases but adapts with prolonged hypoxia (hypoxic ventilatory decline), and
ventilatory sensitivity increases following acclimatization. In contrast,
cerebral blood flow hypoxic sensitivity remains constant over a range of hypoxic
stimuli, with no cerebrovascular acclimatization to sustained hypoxia, suggesting
different mechanisms for O2 sensitivity in the two systems.
PMID- 28705998
TI - Is normobaric hypoxia an effective treatment for sustaining previously acquired
altitude acclimatization?
AB - This study examined whether normobaric hypoxia (NH) treatment is more efficacious
for sustaining high-altitude (HA) acclimatization-induced improvements in
ventilatory and hematologic responses, acute mountain sickness (AMS), and
cognitive function during reintroduction to altitude (RA) than no treatment at
all. Seventeen sea-level (SL) residents (age = 23 +/- 6 yr; means +/- SE)
completed in the following order: 1) 4 days of SL testing; 2) 12 days of HA
acclimatization at 4,300 m; 3) 12 days at SL post-HA acclimatization (Post) where
each received either NH (n = 9, [Formula: see text] = 0.122) or Sham (n = 8;
[Formula: see text] = 0.207) treatment; and 4) 24-h reintroduction to 4,300-m
altitude (RA) in a hypobaric chamber (460 Torr). End-tidal carbon dioxide
pressure ([Formula: see text]), hematocrit (Hct), and AMS cerebral factor score
were assessed at SL, on HA2 and HA11, and after 20 h of RA. Cognitive function
was assessed using the SynWin multitask performance test at SL, on HA1 and HA11,
and after 4 h of RA. There was no difference between NH and Sham treatment, so
data were combined. [Formula: see text] (mmHg) decreased from SL (37.2 +/- 0.5)
to HA2 (32.2 +/- 0.6), decreased further by HA11 (27.1 +/- 0.4), and then
increased from HA11 during RA (29.3 +/- 0.6). Hct (%) increased from SL (42.3 +/-
1.1) to HA2 (45.9 +/- 1.0), increased again from HA2 to HA11 (48.5 +/- 0.8), and
then decreased from HA11 during RA (46.4 +/- 1.2). AMS prevalence (%) increased
from SL (0 +/- 0) to HA2 (76 +/- 11) and then decreased at HA11 (0 +/- 0) and
remained depressed during RA (17 +/- 10). SynWin scores decreased from SL (1,615
+/- 62) to HA1 (1,306 +/- 94), improved from HA1 to HA11 (1,770 +/- 82), and
remained increased during RA (1,707 +/- 75). These results demonstrate that HA
acclimatization-induced improvements in ventilatory and hematologic responses,
AMS, and cognitive function are partially retained during RA after 12 days at SL
whether or not NH treatment is utilized.NEW & NOTEWORTHY This study demonstrates
that normobaric hypoxia treatment over a 12-day period at sea level was not more
effective for sustaining high-altitude (HA) acclimatization during reintroduction
to HA than no treatment at all. The noteworthy aspect is that athletes,
mountaineers, and military personnel do not have to go to extraordinary means to
retain HA acclimatization to an easily accessible and relevant altitude if
reexposure occurs within a 2-wk time period.
PMID- 28705999
TI - Effects of strict prolonged bed rest on cardiorespiratory fitness: systematic
review and meta-analysis.
AB - The aim of this systematic review and meta-analysis [International Prospective
Register of Systematic Reviews (PROSPERO) CRD42017055619] was to assess the
effects of strict prolonged bed rest (without countermeasures) on maximal oxygen
uptake (Vo2max) and to explore sources of variation therein. Since 1949, 80
studies with a total of 949 participants (>90% men) have been published with data
on strict bed rest and Vo2max The studies were conducted mainly in young
participants [median age (interquartile range) 24.5 (22.4-34.0) yr]. The duration
of bed rest ranged from 1 to 90 days. Vo2max declined linearly across bed rest
duration. No statistical difference in the decline among studies reporting Vo2max
as l/min (-0.3% per day) compared with studies reporting Vo2max normalized to
body weight (ml.kg-1.min-1; -0.43% per day) was observed. Although both total
body weight and lean body mass declined in response to bed rest, we did not see
any associations with the decline in Vo2max However, 15-26% of the variation in
the decline in Vo2max was explained by the pre-bed-rest Vo2max levels,
independent of the duration of bed rest (i.e., higher pre-bed-rest Vo2max levels
were associated with larger declines in Vo2max). Furthermore, the systematic
review revealed a gap in the knowledge about the cardiovascular response to
extreme physical inactivity, particularly in older subjects and women of any age
group. In addition to its relevance to spaceflight, this lack of data has
significant translational implications because younger women sometimes undergo
prolonged periods of bed rest associated with the complications of pregnancy and
the incidence of hospitalization including prolonged periods of bed rest
increases with age.NEW & NOTEWORTHY Large interindividual responses of maximal
oxygen uptake (Vo2max) to aerobic exercise training exist. However, less is known
about the variability in the response of Vo2max to prolonged bed rest. This
systematic review and meta-analysis showed that pre-bed-rest Vo2max values were
inversely associated with the change in Vo2max independent of the duration of bed
rest. Moreover, we identified a large knowledge gap about the causes of decline
in Vo2max, particularly in postmenopausal women, which may have clinical
implications.
PMID- 28706000
TI - Absence of compensatory vasodilation with perfusion pressure challenge in
exercise: evidence for and implications of the noncompensator phenotype.
AB - Compromising oxygen delivery (O2D) during exercise requires compensatory
vasodilatory and/or pressor responses to protect O2D:demand matching. The purpose
of the study was to determine whether compensatory vasodilation is absent in some
healthy young individuals in the face of a sudden reduction in exercising forearm
perfusion pressure and whether this affects the exercise pressor response. Twenty
one healthy young men (21.6 +/- 2.0 yr) completed rhythmic forearm exercise at a
work rate equivalent to 70% of their own maximal exercise vasodilation. During
steady-state exercise, the exercising arm was rapidly adjusted from below to
above heart level, resulting in a reduction in forearm perfusion pressure of
30.7 +/- 0.9 mmHg. Forearm blood flow (ml/min; brachial artery Doppler and echo
ultrasound), mean arterial blood pressure (mmHg; finger photoplethysmography),
and exercising forearm venous effluent (antecubital vein catheter) measurements
revealed distinct compensatory vasodilatory differences. Thirteen individuals
responded with compensatory vasodilation (509 +/- 128 vs. 632 +/- 136 ml.min
1.100 mmHg-1; P < 0.001), while eight individuals did not (663 +/- 165 vs. 667 +/
167 ml.min-1.100 mmHg-1; P = 0.6). Compensatory pressor responses between groups
were not different (5.5 +/- 5.5 and 9.7 +/- 9.5 mmHg; P = 0.2). Forearm blood
flow, O2D, and oxygen consumption were all protected in compensators (all P >
0.05) but not in noncompensators, who therefore suffered compromises to exercise
performance (6 +/- 14 vs. -36 +/- 29 N; P = 0.004). Phenotypic differences were
not explained by potassium or nitric oxide bioavailability. In conclusion, both
compensator and noncompensator vasodilator phenotype responses to a sudden
compromise to exercising muscle blood flow are evident. Interindividual
differences in the mechanisms governing O2D:demand matching should be considered
as factors influencing exercise tolerance. NEW & NOTEWORTHY In healthy young
individuals, compromising submaximally exercising muscle perfusion appears to
evoke compensatory vasodilation to defend oxygen delivery. Here we report the
absence of compensatory vasodilation in 8 of 21 such individuals, despite their
vasodilatory capacity and increases in perfusion with increasing exercise
intensity being indistinguishable from compensators. The absence of compensation
impaired exercise tolerance. These findings suggest that interindividual
differences in oxygen delivery:demand matching efficacy affect exercise tolerance
and depend on the nature of a delivery:demand matching challenge.
PMID- 28706001
TI - Aspirin as a COX inhibitor and anti-inflammatory drug in human skeletal muscle.
AB - Although aspirin is one of the most common anti-inflammatory drugs in the world,
the effect of aspirin on human skeletal muscle inflammation is almost completely
unknown. This study examined the potential effects and related time course of an
orally consumed aspirin dose on the inflammatory prostaglandin E2
(PGE2)/cyclooxygenase (COX) pathway in human skeletal muscle. Skeletal muscle
biopsies were taken from the vastus lateralis of 10 healthy adults (5 male and 5
female, 25 +/- 2 yr old) before (Pre) and 2, 4, and 24 h after (Post) a standard
dose (975mg) of aspirin and partitioned for analysis of 1) in vivo PGE2 levels in
resting skeletal muscle and 2) ex vivo skeletal muscle PGE2 production when
stimulated with the COX substrate arachidonic acid (5 MUM). PGE2 levels in vivo
and PGE2 production ex vivo were generally unchanged at each time point after
aspirin consumption. However, most individuals clearly showed suppression of
PGE2, but at varying time points after aspirin consumption. When the maximum
suppression after aspirin consumption was examined for each individual,
independent of time, PGE2 levels in vivo (184 +/- 17 and 104 +/- 23pg/g wet wt at
Pre and Post, respectively) and PGE2 production ex vivo (2.74 +/- 0.17 and 2.09
+/- 0.11pg.mg wet wt-1.min-1 at Pre and Post, respectively) were reduced ( P <
0.05) by 44% and 24%, respectively. These results provide evidence that orally
consumed aspirin can inhibit the COX pathway and reduce the inflammatory mediator
PGE2 in human skeletal muscle. Findings from this study highlight the need to
expand our knowledge regarding the potential role for aspirin regulation of the
deleterious influence of inflammation on skeletal muscle health in aging and
exercising individuals. NEW & NOTEWORTHY This study demonstrated that orally
consumed aspirin can target the prostaglandin/cyclooxygenase pathway in human
skeletal muscle. This pathway has been shown to regulate skeletal muscle
metabolism and inflammation in aging and exercising individuals. Given the
prevalence of aspirin consumption, these findings may have implications for
skeletal muscle health in a large segment of the population.
PMID- 28706002
TI - MicroRNAs That Contribute to Coordinating the Immune Response in Drosophila
melanogaster.
AB - Small noncoding RNAs called microRNAs (miRNAs) have emerged as post
transcriptional regulators of gene expression related to host defenses. Here, we
have used Drosophila melanogaster to explore the contribution of individual or
clusters of miRNAs in countering systemic Candida albicans infection. From a
total of 72 tested, we identify 6 miRNA allelic mutant backgrounds that modulate
the survival response to infection and the ability to control pathogen number.
These mutants also exhibit dysregulation of the Toll pathway target transcripts
Drosomycin (Drs) and Immune-Induced Molecule 1 (IM1). These are characteristics
of defects in Toll signaling, and consistent with this, we demonstrate dependency
for one of the miRNA mutants on the NF-kappaBeta homolog Dif. We also quantify
changes in the miRNA expression profile over time in response to three pathogen
types, and identify 13 mature miRNA forms affected by pathogens that stimulate
Toll signaling. To complement this, we provide a genome-wide map of potential NF
kappaB sites in proximity to miRNA genes. Finally, we demonstrate that systemic
C. albicans infection contributes to a reduction in the total amount of branch
chained amino acids, which is miRNA-regulated. Overall, our data reveal a new
layer of miRNA complexity regulating the fly response to systemic fungal
infection.
PMID- 28706003
TI - Phosphorylation-mediated Regulatory Networks in Mycelia of Pyricularia oryzae
Revealed by Phosphoproteomic Analyses.
AB - Protein phosphorylation is known to regulate pathogenesis, mycelial growth,
conidiation and stress response in Pyricularia oryzae However, phosphorylation
mediated regulatory networks in the fungal pathogen remain largely to be
uncovered. In this study, we identified 1621 phosphorylation sites of 799
proteins in mycelia of P. oryzae, including 899 new p-sites of 536 proteins and
47 new p-sites of 31 pathogenicity-related proteins. From the sequences flanking
the phosphorylation sites, 19 conserved phosphorylation motifs were identified.
Notably, phosphorylation was detected in 7 proteins that function upstream of
Pmk1, but not in Pmk1 and its downstream Mst12 and Sfl1 that have been known to
regulate appressorium formation and infection hyphal growth of P. oryzae
Interestingly, phosphorylation was detected at the site Ser240 of Pmp1, which is
a putative protein phosphatase highly conserved in filamentous fungi but not
characterized. We thus generated Deltapmp1 deletion mutants and dominant allele
PMP1S240D mutants. Phenotyping analyses indicated that Pmp1 is required for
virulence, conidiation and mycelial growth. Further, we observed that
phosphorylation level of Pmk1 in mycelia was significantly increased in the
Deltapmp1 mutant, but decreased in the PMP1S240D mutant in comparison with the
wild type, demonstrating that Pmp1 phosphorylated at Ser240 is important for
regulating phosphorylation of Pmk1. To our surprise, phosphorylation of Mps1,
another MAP kinase required for cell wall integrity and appressorium formation of
P. oryzae, was also significantly enhanced in the Deltapmp1 mutant, but decreased
in the PMP1S240D mutant. In addition, we found that Pmp1 directly interacts with
Mps1 and the region AA180-230 of Pmp1 is required for the interaction. In
summary, this study sheds new lights on the protein phosphorylation mediated
regulatory networks in P. oryzae.
PMID- 28706004
TI - Feedback Microtubule Control and Microtubule-Actin Cross-talk in Arabidopsis
Revealed by Integrative Proteomic and Cell Biology Analysis of KATANIN 1 Mutants.
AB - Microtubule organization and dynamics are critical for key developmental
processes such as cell division, elongation, and morphogenesis. Microtubule
severing is an essential regulator of microtubules and is exclusively executed by
KATANIN 1 in Arabidopsis In this study, we comparatively studied the proteome
wide effects in two KATANIN 1 mutants. Thus, shotgun proteomic analysis of roots
and aerial parts of single nucleotide mutant fra2 and T-DNA insertion mutant ktn1
2 was carried out. We have detected 42 proteins differentially abundant in both
fra2 and ktn1-2 KATANIN 1 dysfunction altered the abundance of proteins involved
in development, metabolism, and stress responses. The differential regulation of
tubulins and microtubule-destabilizing protein MDP25 implied a feedback
microtubule control in KATANIN 1 mutants. Furthermore, deregulation of profilin
1, actin-depolymerizing factor 3, and actin 7 was observed. These findings were
confirmed by immunoblotting analysis of actin and by microscopic observation of
actin filaments using fluorescently labeled phalloidin. Results obtained by
quantitative RT-PCR analysis revealed that changed protein abundances were not a
consequence of altered expression levels of corresponding genes in the mutants.
In conclusion, we show that abundances of several cytoskeletal proteins as well
as organization of microtubules and the actin cytoskeleton are amended in
accordance with defective microtubule severing.
PMID- 28706005
TI - A Cell Wall Proteome and Targeted Cell Wall Analyses Provide Novel Information on
Hemicellulose Metabolism in Flax.
AB - Experimentally-generated (nanoLC-MS/MS) proteomic analyses of four different flax
organs/tissues (inner-stem, outer-stem, leaves and roots) enriched in proteins
from 3 different sub-compartments (soluble-, membrane-, and cell wall-proteins)
was combined with publically available data on flax seed and whole-stem proteins
to generate a flax protein database containing 2996 nonredundant total proteins.
Subsequent multiple analyses (MapMan, CAZy, WallProtDB and expert curation) of
this database were then used to identify a flax cell wall proteome consisting of
456 nonredundant proteins localized in the cell wall and/or associated with cell
wall biosynthesis, remodeling and other cell wall related processes. Examination
of the proteins present in different flax organs/tissues provided a detailed
overview of cell wall metabolism and highlighted the importance of hemicellulose
and pectin remodeling in stem tissues. Phylogenetic analyses of proteins in the
cell wall proteome revealed an important paralogy in the class IIIA xyloglucan
endo-transglycosylase/hydrolase (XTH) family associated with xyloglucan endo
hydrolase activity.Immunolocalisation, FT-IR microspectroscopy, and enzymatic
fingerprinting indicated that flax fiber primary/S1 cell walls contained
xyloglucans with typical substituted side chains as well as glucuronoxylans in
much lower quantities. These results suggest a likely central role of xyloglucans
and endotransglucosylase/hydrolase activity in flax fiber formation and cell wall
remodeling processes.
PMID- 28706007
TI - C-reactive protein gene rs1205 polymorphism is not associated with the risk of
colorectal cancer.
AB - The relationship between C-reactive protein (CRP) gene rs1205 polymorphism and
the risk of colorectal cancer (CRC) has been investigated previously. However,
the results were conflicting. In the present study, we assessed whether CRP gene
rs1205 polymorphism was associated with the risk of CRC by meta-analysis. We
searched in PubMed, Embase, and the CNKI databases. Pooled odds ratios (ORs) and
95% confidence intervals (CIs) were calculated. Seven original studies involving
4,181 cases and 10,601 controls analyzed the association between CRP gene rs1205
polymorphism and CRC risk. No significant association was found between CRP gene
rs1205 polymorphism and CRC risk in this meta-analysis. Sensitivity analysis did
not draw different findings. Stratification analyses of ethnicity, type of
cancer, and genotype method also did not obtain any association between CRP gene
rs1205 polymorphism and CRC risk. In conclusion, this meta-analysis indicates
that CRP gene rs1205 polymorphism was not associated with the risk of CRC.
PMID- 28706006
TI - Integration of flux measurements to resolve changes in anabolic and catabolic
metabolism in cardiac myocytes.
AB - Although ancillary pathways of glucose metabolism are critical for synthesizing
cellular building blocks and modulating stress responses, how they are regulated
remains unclear. In the present study, we used radiometric glycolysis assays,
[13C6]-glucose isotope tracing, and extracellular flux analysis to understand how
phosphofructokinase (PFK)-mediated changes in glycolysis regulate glucose carbon
partitioning into catabolic and anabolic pathways. Expression of kinase-deficient
or phosphatase-deficient 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase in
rat neonatal cardiomyocytes co-ordinately regulated glycolytic rate and lactate
production. Nevertheless, in all groups, >40% of glucose consumed by the cells
was unaccounted for via catabolism to pyruvate, which suggests entry of glucose
carbons into ancillary pathways branching from metabolites formed in the
preparatory phase of glycolysis. Analysis of 13C fractional enrichment patterns
suggests that PFK activity regulates glucose carbon incorporation directly into
the ribose and the glycerol moieties of purines and phospholipids, respectively.
Pyrimidines, UDP-N-acetylhexosamine, and the fatty acyl chains of
phosphatidylinositol and triglycerides showed lower 13C incorporation under
conditions of high PFK activity; the isotopologue 13C enrichment pattern of each
metabolite indicated limitations in mitochondria-engendered aspartate, acetyl CoA
and fatty acids. Consistent with this notion, high glycolytic rate diminished
mitochondrial activity and the coupling of glycolysis to glucose oxidation. These
findings suggest that a major portion of intracellular glucose in cardiac
myocytes is apportioned for ancillary biosynthetic reactions and that PFK co
ordinates the activities of the pentose phosphate, hexosamine biosynthetic, and
glycerolipid synthesis pathways by directly modulating glycolytic intermediate
entry into auxiliary glucose metabolism pathways and by indirectly regulating
mitochondrial cataplerosis.
PMID- 28706008
TI - Efficacy and safety of bortezomib maintenance in patients with newly diagnosed
multiple myeloma: a meta-analysis.
AB - Multiple myeloma (MM) is a B-cell neoplasm with a high incidence of relapse.
Bortezomib has been extensively studied for the maintenance treatment of MM.
Here, we carried out a meta-analysis to determine the efficacy and safety of
maintenance therapy with bortezomib. We searched for clinical trials in PubMed
(Medline), Embase (OVID), and the Cochrane Library. Two randomized controlled
trials (RCTs) enrolling a total of 1338 patients were included. Bortezomib
maintenance statistically significantly improved both progression-free survival
(PFS) (hazard ratio (HR) 0.67, 95% confidence interval (CI) = 0.51 to 0.87,
P=0.003) and overall survival (OS) (HR = 0.75 therapy, 95% CI = 0.63 to 0.89,
P=0.001) more than did non-bortezomib maintenance therapy. Our analysis revealed
higher incidence of neutropenia (risks ratios (RR) = 1.39; 95% CI = 1.08 to
1.79), peripheral neuropathy (PN) (RR = 2.23; 95% CI = 1.38 to 3.61, P=0.001),
and cardiologic events (RR = 1.91; 95% CI = 1.12 to 3.28, P=0.02) in patients
with bortezomib maintenance therapy. Our meta-analysis demonstrates OS and PFS
benefits of bortezomib maintenance therapy in patients with newly diagnosed MM.
However, the therapy is associated with increased risk of adverse events.
Additionally, more RCTs are needed for better understanding and determination of
optimal bortezomib maintenance therapy in MM.
PMID- 28706009
TI - Perceptions of Cancer Care and Clinical Trials in the Black Community:
Implications for Care Coordination Between Oncology and Primary Care Teams.
AB - BACKGROUND: Despite efforts to ameliorate disparities in cancer care and clinical
trials, barriers persist. As part of a multiphase community-engaged assessment,
an exploratory community-engaged research partnership, forged between an academic
hospital and a community-based organization, set out to explore perceptions of
cancer care and cancer clinical trials by black Bostonians. MATERIALS AND
METHODS: Key informant interviews with health care providers and patient
advocates in community health centers (CHCs), organizers from grassroots
coalitions focused on cancer, informed the development of a focus group protocol.
Six focus groups were conducted with black residents in Boston, including groups
of cancer survivors and family members. Transcripts were coded thematically and a
code-based report was generated and analyzed by community and academic
stakeholders. RESULTS: While some participants identified clinical trials as
beneficial, overall perceptions conjured feelings of fear and exploitation.
Participants describe barriers to clinical trial participation in the context of
cancer care experiences, which included negative interactions with providers and
mistrust. Primary care physicians (PCPs) reported being levied as a trusted
resource for patients undergoing care, but lamented the absence of a mechanism by
which to gain information about cancer care and clinical trials. CONCLUSIONS:
Confusion about cancer care and clinical trials persists, even among individuals
who have undergone treatment for cancer. Greater coordination between PCPs and
CHC care teams and oncology care teams may improve patient experiences with
cancer care, while also serving as a mechanism to disseminate information about
treatment options and clinical trials. IMPLICATIONS FOR PRACTICE: Inequities in
cancer care and clinical trial participation persist. The findings of this study
indicate that greater coordination with primary care physicians (PCPs) and
community health center (CHC) providers may be an important step for both
improving the quality of cancer care in communities and increasing awareness of
clinical trials. However, PCPs and CHCs are often stretched to capacity with
caring for their communities. This leaves the oncology community well positioned
to create programs to bridge the communication gaps and provide resources
necessary to support oncologic care along the cancer continuum, from prevention
through survivorship.
PMID- 28706010
TI - Clinical Management of Potential Toxicities and Drug Interactions Related to
Cyclin-Dependent Kinase 4/6 Inhibitors in Breast Cancer: Practical Considerations
and Recommendations.
AB - : Aberrations of the cell cycle are pervasive in cancer, and selective cell cycle
inhibition of cancer cells is a target of choice for a number of novel cancer
therapeutics. Cyclin-dependent kinases (CDKs) are key regulatory enzymes that
control cell cycle transitions and the commitment to cell division. Palbociclib
and ribociclib are both orally active, highly selective reversible inhibitors of
CDK4 and CDK6 that are approved by the U.S. Food and Drug Administration (FDA)
for hormone receptor-positive metastatic breast cancer in combination with
specific endocrine therapies. A third oral CDK4/6 inhibitor, abemaciclib,
received Breakthrough Therapy designation status from the FDA and is also being
developed in breast cancer. The most common adverse events associated with
palbociclib and ribociclib are hematologic, particularly neutropenia. However,
the neutropenia associated with CDK4/6 inhibitors is distinct from chemotherapy
induced neutropenia in that it is rapidly reversible, reflecting a cytostatic
effect on neutrophil precursors in the bone marrow. Most hematologic
abnormalities seen with CDK4/6 inhibitors are not complicated and are adequately
managed with standard supportive care and dose adjustments when indicated.
Cytopenias are less prevalent with abemaciclib, although fatigue and
gastrointestinal toxicity is more common with this agent. This review focuses on
the clinical management of potential toxicities and drug interactions seen with
the use of CDK4/6 inhibitors in breast cancer, with a focus on palbociclib and
ribociclib, and summarizes practical management strategies for an oncologist.
IMPLICATIONS FOR PRACTICE: The emergence of modern cyclin-dependent kinase (CDK)
inhibitors has changed the treatment paradigm for metastatic hormone receptor
(HR)-positive breast cancer. Palbociclib, ribociclib, and abemaciclib are highly
selective reversible inhibitors of CDK4 and CDK6. Palbociclib is U.S. Food and
Drug Administration (FDA)-approved in the first- and second-line settings in
combination with endocrine therapy for HR-positive metastatic breast cancer.
Ribociclib is FDA-approved in the first-line setting. Abemaciclib has received
FDA Breakthrough Therapy designation status. This review focuses on the clinical
management of potential toxicities and drug interactions seen with the use of
CDK4/6 inhibitors in breast cancer.
PMID- 28706011
TI - Increased IFNgamma+ T Cells Are Responsible for the Clinical Responses of Low
Dose DNA-Demethylating Agent Decitabine Antitumor Therapy.
AB - Purpose: Low-dose DNA-demethylating agent decitabine therapy is effective in a
subgroup of cancer patients. It remains largely elusive for the biomarker to
predict therapeutic response and the underlying antitumor mechanisms, especially
the impact on host antitumor immunity.Experimental Design: The influence of low
dose decitabine on T cells was detected both in vitro and in vivo Moreover, a
test cohort and a validation cohort of advanced solid tumor patients with low
dose decitabine-based treatment were involved. The activation, proliferation,
polarization, and cytolysis capacity of CD3+ T cells were analyzed by FACS and
CCK8 assay. Kaplan-Meier and Cox proportional hazard regression analysis were
performed to investigate the prognostic value of enhanced T-cell activity
following decitabine epigenetic therapy.Results: Low-dose decitabine therapy
enhanced the activation and proliferation of human IFNgamma+ T cells, promoted
Th1 polarization and activity of cytotoxic T cells both in vivo and in vitro,
which in turn inhibited cancer progression and augmented the clinical effects of
patients. In clinical trials, increased IFNgamma+ T cells and increased T-cell
cytotoxicity predicted improved therapeutic responses and survival in the test
cohort and validation cohort.Conclusions: We find that low-dose decitabine
therapy promotes antitumor T-cell responses by promoting T-cell proliferation and
the increased IFNgamma+ T cells may act as a potential prognostic biomarker for
the response to decitabine-based antitumor therapy. Clin Cancer Res; 23(20); 6031
43. (c)2017 AACR.
PMID- 28706012
TI - Local Delivery of OncoVEXmGM-CSF Generates Systemic Antitumor Immune Responses
Enhanced by Cytotoxic T-Lymphocyte-Associated Protein Blockade.
AB - Purpose: Talimogene laherparepvec, a new oncolytic immunotherapy, has been
recently approved for the treatment of melanoma. Using a murine version of the
virus, we characterized local and systemic antitumor immune responses driving
efficacy in murine syngeneic models.Experimental Design: The activity of
talimogene laherparepvec was characterized against melanoma cell lines using an
in vitro viability assay. Efficacy of OncoVEXmGM-CSF (talimogene laherparepvec
with the mouse granulocyte-macrophage colony-stimulating factor transgene) alone
or in combination with checkpoint blockade was characterized in A20 and CT-26
contralateral murine tumor models. CD8+ depletion, adoptive T-cell transfers, and
Enzyme-Linked ImmunoSpot assays were used to study the mechanism of action (MOA)
of systemic immune responses.Results: Treatment with OncoVEXmGM-CSF cured all
injected A20 tumors and half of contralateral tumors. Viral presence was limited
to injected tumors and was not responsible for systemic efficacy. A significant
increase in T cells (CD3+/CD8+) was observed in injected and contralateral tumors
at 168 hours. Ex vivo analyses showed these cytotoxic T lymphocytes were tumor
specific. Increased neutrophils, monocytes, and chemokines were observed in
injected tumors only. Importantly, depletion of CD8+ T cells abolished all
systemic efficacy and significantly decreased local efficacy. In addition, immune
cell transfer from OncoVEXmGM-CSF-cured mice significantly protected from tumor
challenge. Finally, combination of OncoVEXmGM-CSF and checkpoint blockade
resulted in increased tumor-specific CD8+ anti-AH1 T cells and systemic
efficacy.Conclusions: The data support a dual MOA for OncoVEXmGM-CSF that
involves direct oncolysis of injected tumors and activation of a CD8+-dependent
systemic response that clears injected and contralateral tumors when combined
with checkpoint inhibition. Clin Cancer Res; 23(20); 6190-202. (c)2017 AACR.
PMID- 28706013
TI - Comment on "Molecular and neural basis of contagious itch behavior in mice".
AB - Yu et al (Reports, 10 March 2017, p. 1072) state that contagious itch occurs in
mice based on imitative scratching in normal mice observing excessive scratching
in genetically modified demonstrator mice. However, despite employing multiple
behavioral analysis approaches, we were unable to extend these findings to normal
mice observing the well-established histamine model of acute itch in demonstrator
mice.
PMID- 28706014
TI - Response to Comment on "Molecular and neural basis of contagious itch behavior in
mice".
AB - Liljencrantz et al report the failure of observing contagious itch behavior using
mice injected with histamine as the demonstrators. Analysis of their results
shows that the histamine model is limited by inadequate frequency and duration of
scratching bouts required for contagious itch test. To streamline the contagious
itch test, the screen paradigm is highly recommended.
PMID- 28706015
TI - Can we beat influenza?
PMID- 28706016
TI - News at a glance.
PMID- 28706017
TI - Labmade smallpox is possible, study shows.
PMID- 28706019
TI - CubeSat networks hasten shift to commercial weather data.
PMID- 28706018
TI - Trump's science shop is small and waiting for leadership.
PMID- 28706020
TI - A trans-Atlantic transparency gap on animal experiments.
PMID- 28706021
TI - A push for low-carbon fuels pays off in California.
PMID- 28706022
TI - Surviving the cure.
PMID- 28706023
TI - A raven's memories are for the future.
PMID- 28706024
TI - The importance of being modular.
PMID- 28706025
TI - Immunology taught by rats.
PMID- 28706026
TI - Of sizzling steaks and DNA repair.
PMID- 28706027
TI - Plasmonic imaging is gaining momentum.
PMID- 28706028
TI - How do miniproteins fold?
PMID- 28706029
TI - When early adopters don't adopt.
PMID- 28706030
TI - The Sun spotters.
PMID- 28706031
TI - The elegant law that governs us all.
PMID- 28706032
TI - Publish openly but responsibly.
PMID- 28706033
TI - Publish openly but responsibly-Response.
PMID- 28706034
TI - Indigenous peoples: Conservation paradox.
PMID- 28706035
TI - Outbreak.
PMID- 28706036
TI - Driving improvements in emerging disease surveillance through locally relevant
capacity strengthening.
AB - Emerging infectious diseases (EIDs) threaten the health of people, animals, and
crops globally, but our ability to predict their occurrence is limited. Current
public health capacity and ability to detect and respond to EIDs is typically
weakest in low- and middle-income countries (LMICs). Many known drivers of EID
emergence also converge in LMICs. Strengthening capacity for surveillance of
diseases of relevance to local populations can provide a mechanism for building
the cross-cutting and flexible capacities needed to tackle both the burden of
existing diseases and EID threats. A focus on locally relevant diseases in LMICs
and the economic, social, and cultural contexts of surveillance can help address
existing inequalities in health systems, improve the capacity to detect and
contain EIDs, and contribute to broader global goals for development.
PMID- 28706037
TI - Opportunities and challenges in modeling emerging infectious diseases.
AB - The term "pathogen emergence" encompasses everything from previously unidentified
viruses entering the human population to established pathogens invading new
populations and the evolution of drug resistance. Mathematical models of emergent
pathogens allow forecasts of case numbers, investigation of transmission
mechanisms, and evaluation of control options. Yet, there are numerous
limitations and pitfalls to their use, often driven by data scarcity. Growing
availability of data on pathogen genetics and human ecology, coupled with
computational and methodological innovations, is amplifying the power of models
to inform the public health response to emergence events. Tighter integration of
infectious disease models with public health practice and development of
resources at the ready has the potential to increase the timeliness and quality
of responses.
PMID- 28706038
TI - Improving vaccine trials in infectious disease emergencies.
AB - Unprecedented global effort is under way to facilitate the testing of
countermeasures in infectious disease emergencies. Better understanding of the
various options for trial design is needed in advance of outbreaks, as is
preliminary global agreement on the most suitable designs for the various
scenarios. What would enhance the speed, validity, and ethics of clinical studies
of such countermeasures? Focusing on studies of vaccine efficacy and
effectiveness in emergencies, we highlight three needs: for formal randomized
trials-even in most emergencies; for individually randomized trials-even in many
emergencies; and for six areas of innovation in trial methodology. These needs
should inform current updates of protocols and roadmaps.
PMID- 28706039
TI - When an emerging disease becomes endemic.
AB - Epidemics, such as HIV in the early 1980s and Ebola in 2014, inspire decisive
government investment and action, and individual and societal concern, sometimes
bordering on panic. By contrast, endemic diseases, such as HIV in 2017 and
tuberculosis, struggle to maintain the same attention. For many, the paradox is
that endemic disease, in its totality, continues to impose a far higher public
health burden than epidemic disease. Overall, the swift political response to
epidemics has resulted in success. It has proven possible to eradicate epidemic
diseases, often without the availability of vaccines and other biomedical
technologies. In recent times, only HIV has made the transition from epidemic to
endemic, but diseases that have existed for centuries continue to cause most of
the infectious disease burden.
PMID- 28706040
TI - Is the Sun a solar-type star?
PMID- 28706041
TI - Diamonds to the rescue.
PMID- 28706042
TI - The brain circuits of a winner.
PMID- 28706043
TI - Amyloid impairs synaptic trafficking.
PMID- 28706044
TI - Making a plan.
PMID- 28706045
TI - New York City rats provide a gift to virologists.
PMID- 28706046
TI - A triple search for coupling reactions.
PMID- 28706047
TI - Intergenerational transcription taming.
PMID- 28706048
TI - Divided, they conquer.
PMID- 28706049
TI - Modularity limits disturbance effects.
PMID- 28706050
TI - Making an oxide-layered antiferromagnet.
PMID- 28706051
TI - Exploring structure space to understand stability.
PMID- 28706052
TI - Heat-loving quantum oscillations.
PMID- 28706053
TI - Plasmons probe the quantum response.
PMID- 28706054
TI - Distinct neural patterns for two languages.
PMID- 28706055
TI - Not-so-sweet DNA damage repaired.
PMID- 28706056
TI - Curbing culprits of chronic rejection.
PMID- 28706057
TI - Meteorites formed in two reservoirs.
PMID- 28706058
TI - Mechanisms for maintaining mental maps.
PMID- 28706059
TI - A microglia type associated with AD.
PMID- 28706060
TI - Late to the party.
PMID- 28706061
TI - Bulking up algae for biofuels.
PMID- 28706062
TI - Growing nanosheets off nanowires.
PMID- 28706063
TI - Bumble bees create a buzz.
PMID- 28706064
TI - History of winning remodels thalamo-PFC circuit to reinforce social dominance.
AB - Mental strength and history of winning play an important role in the
determination of social dominance. However, the neural circuits mediating these
intrinsic and extrinsic factors have remained unclear. Working in mice, we
identified a dorsomedial prefrontal cortex (dmPFC) neural population showing
"effort"-related firing during moment-to-moment competition in the dominance tube
test. Activation or inhibition of the dmPFC induces instant winning or losing,
respectively. In vivo optogenetic-based long-term potentiation and depression
experiments establish that the mediodorsal thalamic input to the dmPFC mediates
long-lasting changes in the social dominance status that are affected by history
of winning. The same neural circuit also underlies transfer of dominance between
different social contests. These results provide a framework for understanding
the circuit basis of adaptive and pathological social behaviors.
PMID- 28706066
TI - Snap deconvolution: An informatics approach to high-throughput discovery of
catalytic reactions.
AB - We present an approach to multidimensional high-throughput discovery of catalytic
coupling reactions that integrates molecular design with automated analysis and
interpretation of mass spectral data. We simultaneously assessed the reactivity
of three pools of compounds that shared the same functional groups (halides,
boronic acids, alkenes, and alkynes, among other groups) but carried inactive
substituents having specifically designed differences in masses. The substituents
were chosen such that the products from any class of reaction in multiple
reaction sets would have unique differences in masses, thus allowing simultaneous
identification of the products of all transformations in a set of reactants. In
this way, we easily distinguished the products of new reactions from noise and
known couplings. Using this method, we discovered an alkyne hydroallylation and a
nickel-catalyzed variant of alkyne diarylation.
PMID- 28706065
TI - Global analysis of protein folding using massively parallel design, synthesis,
and testing.
AB - Proteins fold into unique native structures stabilized by thousands of weak
interactions that collectively overcome the entropic cost of folding. Although
these forces are "encoded" in the thousands of known protein structures,
"decoding" them is challenging because of the complexity of natural proteins that
have evolved for function, not stability. We combined computational protein
design, next-generation gene synthesis, and a high-throughput protease
susceptibility assay to measure folding and stability for more than 15,000 de
novo designed miniproteins, 1000 natural proteins, 10,000 point mutants, and
30,000 negative control sequences. This analysis identified more than 2500 stable
designed proteins in four basic folds-a number sufficient to enable us to
systematically examine how sequence determines folding and stability in uncharted
protein space. Iteration between design and experiment increased the design
success rate from 6% to 47%, produced stable proteins unlike those found in
nature for topologies where design was initially unsuccessful, and revealed
subtle contributions to stability as designs became increasingly optimized. Our
approach achieves the long-standing goal of a tight feedback cycle between
computation and experiment and has the potential to transform computational
protein design into a data-driven science.
PMID- 28706067
TI - High-temperature quantum oscillations caused by recurring Bloch states in
graphene superlattices.
AB - Cyclotron motion of charge carriers in metals and semiconductors leads to Landau
quantization and magneto-oscillatory behavior in their properties. Cryogenic
temperatures are usually required to observe these oscillations. We show that
graphene superlattices support a different type of quantum oscillation that does
not rely on Landau quantization. The oscillations are extremely robust and
persist well above room temperature in magnetic fields of only a few tesla. We
attribute this phenomenon to repetitive changes in the electronic structure of
superlattices such that charge carriers experience effectively no magnetic field
at simple fractions of the flux quantum per superlattice unit cell. Our work
hints at unexplored physics in Hofstadter butterfly systems at high temperatures.
PMID- 28706068
TI - Reconciling solar and stellar magnetic cycles with nonlinear dynamo simulations.
AB - The magnetic fields of solar-type stars are observed to cycle over decadal
periods-11 years in the case of the Sun. The fields originate in the turbulent
convective layers of stars and have a complex dependency upon stellar rotation
rate. We have performed a set of turbulent global simulations that exhibit
magnetic cycles varying systematically with stellar rotation and luminosity. We
find that the magnetic cycle period is inversely proportional to the Rossby
number, which quantifies the influence of rotation on turbulent convection. The
trend relies on a fundamentally nonlinear dynamo process and is compatible with
the Sun's cycle and those of other solar-type stars.
PMID- 28706069
TI - All-oxide-based synthetic antiferromagnets exhibiting layer-resolved
magnetization reversal.
AB - Synthesizing antiferromagnets with correlated oxides has been challenging, owing
partly to the markedly degraded ferromagnetism of the magnetic layer at nanoscale
thicknesses. Here we report on the engineering of an antiferromagnetic interlayer
exchange coupling (AF-IEC) between ultrathin but ferromagnetic La2/3Ca1/3MnO3
layers across an insulating CaRu1/2Ti1/2O3 spacer. The layer-resolved magnetic
switching leads to sharp steplike hysteresis loops with magnetization plateaus
depending on the repetition number of the stacking bilayers. The magnetization
configurations can be switched at moderate fields of hundreds of oersted.
Moreover, the AF-IEC can also be realized with an alternative magnetic layer of
La2/3Sr1/3MnO3 that possesses a Curie temperature near room temperature. The
findings will add functionalities to devices with correlated-oxide interfaces.
PMID- 28706070
TI - Control and local measurement of the spin chemical potential in a magnetic
insulator.
AB - The spin chemical potential characterizes the tendency of spins to diffuse.
Probing this quantity could provide insight into materials such as magnetic
insulators and spin liquids and aid optimization of spintronic devices. Here we
introduce single-spin magnetometry as a generic platform for nonperturbative,
nanoscale characterization of spin chemical potentials. We experimentally realize
this platform using diamond nitrogen-vacancy centers and use it to investigate
magnons in a magnetic insulator, finding that the magnon chemical potential can
be controlled by driving the system's ferromagnetic resonance. We introduce a
symmetry-based two-fluid theory describing the underlying magnon processes,
measure the local thermomagnonic torque, and illustrate the detection sensitivity
using electrically controlled spin injection. Our results pave the way for
nanoscale control and imaging of spin transport in mesoscopic systems.
PMID- 28706071
TI - Effects of network modularity on the spread of perturbation impact in
experimental metapopulations.
AB - Networks with a modular structure are expected to have a lower risk of global
failure. However, this theoretical result has remained untested until now. We
used an experimental microarthropod metapopulation to test the effect of
modularity on the response to perturbation. We perturbed one local population and
measured the spread of the impact of this perturbation, both within and between
modules. Our results show the buffering capacity of modular networks. To assess
the generality of our findings, we then analyzed a dynamical model of our system.
We show that in the absence of perturbations, modularity is negatively correlated
with metapopulation size. However, even when a small local perturbation occurs,
this negative effect is offset by a buffering effect that protects the majority
of the nodes from the perturbation.
PMID- 28706072
TI - Ravens parallel great apes in flexible planning for tool-use and bartering.
AB - The ability to flexibly plan for events outside of the current sensory scope is
at the core of being human and is crucial to our everyday lives and society.
Studies on apes have shaped a belief that this ability evolved within the hominid
lineage. Corvids, however, have shown evidence of planning their food hoarding,
although this has been suggested to reflect a specific caching adaptation rather
than domain-general planning. Here, we show that ravens plan for events unrelated
to caching-tool-use and bartering-with delays of up to 17 hours, exert self
control, and consider temporal distance to future events. Their performance
parallels that seen in apes and suggests that planning evolved independently in
corvids, which opens new avenues for the study of cognitive evolution.
PMID- 28706073
TI - Mouse models of acute and chronic hepacivirus infection.
AB - An estimated 71 million people worldwide are infected with hepatitis C virus
(HCV). The lack of small-animal models has impeded studies of antiviral immune
mechanisms. Here we show that an HCV-related hepacivirus discovered in Norway
rats can establish high-titer hepatotropic infections in laboratory mice with
immunological features resembling those seen in human viral hepatitis. Whereas
immune-compromised mice developed persistent infection, immune-competent mice
cleared the virus within 3 to 5 weeks. Acute clearance was T cell dependent and
associated with liver injury. Transient depletion of CD4+ T cells before
infection resulted in chronic infection, characterized by high levels of
intrahepatic regulatory T cells and expression of inhibitory molecules on
intrahepatic CD8+ T cells. Natural killer cells controlled early infection but
were not essential for viral clearance. This model may provide mechanistic
insights into hepatic antiviral immunity, a prerequisite for the development of
HCV vaccines.
PMID- 28706074
TI - Germ line-inherited H3K27me3 restricts enhancer function during maternal-to
zygotic transition.
AB - Gametes carry parental genetic material to the next generation. Stress-induced
epigenetic changes in the germ line can be inherited and can have a profound
impact on offspring development. However, the molecular mechanisms and
consequences of transgenerational epigenetic inheritance are poorly understood.
We found that Drosophila oocytes transmit the repressive histone mark H3K27me3 to
their offspring. Maternal contribution of the histone methyltransferase Enhancer
of zeste, the enzymatic component of Polycomb repressive complex 2, is required
for active propagation of H3K27me3 during early embryogenesis. H3K27me3 in the
early embryo prevents aberrant accumulation of the active histone mark H3K27ac at
regulatory regions and precocious activation of lineage-specific genes at zygotic
genome activation. Disruption of the germ line-inherited Polycomb epigenetic
memory causes embryonic lethality that cannot be rescued by late zygotic
reestablishment of H3K27me3. Thus, maternally inherited H3K27me3, propagated in
the early embryo, regulates the activation of enhancers and lineage-specific
genes during development.
PMID- 28706076
TI - Academia needs to confront sexism.
PMID- 28706078
TI - Chronic hepatitis B: divide and conquer?
PMID- 28706079
TI - Can we prevent and modify cardiometabolic disorders by controlling HCV infection?
PMID- 28706080
TI - Power-up: A Reanalysis of 'Power Failure' in Neuroscience Using Mixture Modeling.
AB - Recently, evidence for endemically low statistical power has cast neuroscience
findings into doubt. If low statistical power plagues neuroscience, then this
reduces confidence in the reported effects. However, if statistical power is not
uniformly low, then such blanket mistrust might not be warranted. Here, we
provide a different perspective on this issue, analyzing data from an influential
study reporting a median power of 21% across 49 meta-analyses (Button et al.,
2013). We demonstrate, using Gaussian mixture modeling, that the sample of 730
studies included in that analysis comprises several subcomponents so the use of a
single summary statistic is insufficient to characterize the nature of the
distribution. We find that statistical power is extremely low for studies
included in meta-analyses that reported a null result and that it varies
substantially across subfields of neuroscience, with particularly low power in
candidate gene association studies. Therefore, whereas power in neuroscience
remains a critical issue, the notion that studies are systematically underpowered
is not the full story: low power is far from a universal problem.SIGNIFICANCE
STATEMENT Recently, researchers across the biomedical and psychological sciences
have become concerned with the reliability of results. One marker for reliability
is statistical power: the probability of finding a statistically significant
result given that the effect exists. Previous evidence suggests that statistical
power is low across the field of neuroscience. Our results present a more
comprehensive picture of statistical power in neuroscience: on average, studies
are indeed underpowered-some very seriously so-but many studies show acceptable
or even exemplary statistical power. We show that this heterogeneity in
statistical power is common across most subfields in neuroscience. This new, more
nuanced picture of statistical power in neuroscience could affect not only
scientific understanding, but potentially policy and funding decisions for
neuroscience research.
PMID- 28706081
TI - Brief Stimulus Exposure Fully Remediates Temporal Processing Deficits Induced by
Early Hearing Loss.
AB - In childhood, partial hearing loss can produce prolonged deficits in speech
perception and temporal processing. However, early therapeutic interventions
targeting temporal processing may improve later speech-related outcomes. Gap
detection is a measure of auditory temporal resolution that relies on the
auditory cortex (ACx), and early auditory deprivation alters intrinsic and
synaptic properties in the ACx. Thus, early deprivation should induce deficits in
gap detection, which should be reflected in ACx gap sensitivity. We tested
whether earplugging-induced, early transient auditory deprivation in male and
female Mongolian gerbils caused correlated deficits in behavioral and cortical
gap detection, and whether these could be rescued by a novel therapeutic
approach: brief exposure to gaps in background noise. Two weeks after earplug
removal, animals that had been earplugged from hearing onset throughout auditory
critical periods displayed impaired behavioral gap detection thresholds (GDTs),
but this deficit was fully reversed by three 1 h sessions of exposure to gaps in
noise. In parallel, after earplugging, cortical GDTs increased because fewer
cells were sensitive to short gaps, and gap exposure normalized this pattern.
Furthermore, in deprived animals, both first-spike latency and first-spike
latency jitter increased, while spontaneous and evoked firing rates decreased,
suggesting that deprivation causes a wider range of perceptual problems than
measured here. These cortical changes all returned to control levels after gap
exposure. Thus, brief stimulus exposure, perhaps in a salient context such as the
unfamiliar placement into a testing apparatus, rescued impaired gap detection and
may have potential as a remediation tool for general auditory processing
deficits.SIGNIFICANCE STATEMENT Hearing loss in early childhood leads to
impairments in auditory perception and language processing that can last well
beyond the restoration of hearing sensitivity. Perceptual deficits can be
improved by training, or by acoustic enrichment in animal models, but both
approaches involve extended time and effort. Here, we used a novel remediation
technique, brief periods of auditory stimulus exposure, to fully remediate
cortical and perceptual deficits in gap detection induced by early transient
hearing loss. This technique also improved multiple cortical response properties.
Rescue by this efficient exposure regime may have potential as a therapeutic tool
to remediate general auditory processing deficits in children with perceptual
challenges arising from early hearing loss.
PMID- 28706082
TI - Postural sway, working years and BMI in healthy truck drivers: an observational
study.
AB - OBJECTIVES: The following study analyses the influence of risk factors among the
occupational group of truck drivers on postural control and body mass index
(BMI). DESIGN: Observational study. SETTING: One motorway station close to
several highways in Germany. PARTICIPANTS: 180 truck drivers (177 male/3 female),
aged 21-65 years old, took part in this study. OUTCOME MEASURES: Postural control
was examined using a pressure plate. In order to examine the influence of body
weight (BMI) and working years on postural control, subjects were divided into
samples of five and three groups, respectively. Furthermore, it was evaluated
whether the subjects suffered from back pain. For data analysis, the Kruskal
Wallis test was used as the data were not normally distributed. Once the p value
of the Kruskal-Wallis test was p<=0.05, the Conover-Iman comparison and
afterwards the Bonferroni-Holm correction were used. The significance level was
set at alpha <=0.05. RESULTS: Regarding the number of working years, a
significant increase of frontal (p<=0.04) and sagittal (p<=0.001) sway were
observed. The correlation of the five BMI groups with the number of working years
demonstrates that an increase of the working years leads to an increase of BMI
(p<=0.03). Furthermore, the majority of truck drivers participating in this study
suffered from back pain (61.7%). CONCLUSIONS: BMI and musculoskeletal impairment
are indicators of health risk factors. In this study, it is shown that an
increasing number of working years and an increasing BMI lead to a decrease in
frontal and sagittal postural sway. In addition, the number of working years
correlates with body weight and back pain.
PMID- 28706083
TI - Wealth-related inequality in early uptake of HIV testing among pregnant women: an
analysis of data from a national cross-sectional survey, South Africa.
AB - OBJECTIVES: Wealth-related inequality across the South African antenatal HIV care
cascade has not been considered in detail as a potential hindrance to eliminating
mother-to-child HIV transmission (EMTCT). We aimed to measure wealth-related
inequality in early (before enrolling into antenatal care) uptake of HIV testing
and identify the contributing determinants. DESIGN: Cross-sectional survey.
SETTINGS: South African primary public health facilities in 2012. PARTICIPANTS: A
national-level sample of 8618 pregnant women. OUTCOME MEASURES: Wealth-related
inequality in early uptake of HIV testing was measured using the Erreygers
concentration index (CI) further adjusted for inequality introduced by predicted
healthcare need (ie, need-standardised). Determinants contributing to the
observed inequality were identified using the Erreygers and Wagstaff
decomposition methods. RESULTS: Participants were aged 13 to 49 years. Antenatal
HIV prevalence was 33.2%, of which 43.7% came from the lowest 40% wealth group. A
pro-poor wealth-related inequality in early HIV testing was observed. The need
standardised concentration index was -0.030 (95% confidence interval -0.038 to
0.022). The proportion of early HIV testing was significantly better in the lower
40% wealth group compared with the higher 40% wealth group (p value=0.040). The
largest contributions to the observed inequality were from underlying
inequalities in province (contribution, 65.27%), age (-44.38%), wealth group
(24.73%) and transport means (21.61%). CONCLUSIONS: Our results on better early
uptake of HIV testing among the poorer subpopulation compared with the richer
highlights inequity in uptake of HIV testing in South Africa. This socioeconomic
difference could contribute to fast-tracking EMTCT given the high HIV prevalence
among the lower wealth group. The high contribution of provinces and age to
inequality highlights the need to shift from reliance on national-level estimates
alone but identify subregional-specific and age-specific bottlenecks. Future
interventions need to be context specific and tailored for specific
subpopulations and subregional settings.
PMID- 28706084
TI - Rationale and protocol for the After Diabetes Diagnosis REsearch Support System
(ADDRESS): an incident and high risk type 1 diabetes UK cohort study.
AB - INTRODUCTION: Type 1 diabetes is heterogeneous in its presentation and
progression. Variations in clinical presentation between children and adults, and
with ethnic group warrant further study in the UK to improve understanding of
this heterogeneity. Early interventions to limit beta cell damage in type 1
diabetes are undergoing evaluation, but recruitment is challenging. The protocol
presented describes recruitment of people with clinician-assigned, new-onset type
1 diabetes to understand the variation in their manner of clinical presentation,
to facilitate recruitment into intervention studies and to create an open-access
resource of data and biological samples for future type 1 diabetes research.
METHODS AND ANALYSIS: Using the National Institute for Health Research Clinical
Research Network, patients >5 years of age diagnosed clinically with type 1
diabetes (and their siblings) are recruited within 6 months of diagnosis.
Participants agree to have their clinical, laboratory and demographic data stored
on a secure database, for their clinical progress to be monitored using
information held by NHS Digital, and to be contacted about additional research,
in particular immunotherapy and other interventions. An optional blood sample is
taken for islet autoantibody measurement and storage of blood and DNA for future
analyses. Data will be analysed statistically to describe the presentation of
incident type 1 diabetes in a contemporary UK population. ETHICS AND
DISSEMINATION: Ethical approval was obtained from the independent NHS Research
Ethics Service. Results will be presented at national and international meetings
and submitted for publication to peer-reviewed journals.
PMID- 28706085
TI - Effectiveness of government anti-smoking policy on non-smoking youth in Korea: a
4-year trend analysis of national survey data.
AB - OBJECTIVES: Since the Health Promotion Act was introduced in Korea in 1995, anti
smoking policies and regulations have undergone numerous revisions, and non
smoking areas have gradually been expanded. The purpose of this study was to
examine the impact of a partial legislative ban on adolescent exposure to
secondhand smoke using objective urinary cotinine levels in a nationwide
representative sample. METHODS: Urine cotinine levels were measured in the Korea
National Health and Nutrition Examination Survey from 2008 to 2011. This study
was a trend analysis of 4 years of national survey data from 2197 Korean youth
aged 10-18 years. Among non-smokers, the 75th percentile urinary cotinine level
was estimated. We also considered the number of household smokers. RESULTS: The
75th percentile urine cotinine level of non-smokers showed a significant
decreasing trend from 2008 to 2011, from 15.47 to 5.37 ng/mL, respectively. Urine
cotinine did not decline significantly in non-smokers living with smokers during
the study period. The results did not show a statistically significant reduction
in smoking rate in adolescents from 2008 to 2011, although there was a trend
towards a decrease (p=0.081). CONCLUSIONS: Based on urine cotinine levels,
government-initiated anti-smoking policies have only been effective among highly
exposed non-smoking adolescents during the study period. Further study needs to
evaluate whether or not the legislative ban affects domestic smoking exposure.
PMID- 28706086
TI - Efficacy of home-based non-pharmacological interventions for treating depression:
a systematic review and network meta-analysis of randomised controlled trials.
AB - OBJECTIVES: To systematically review and compare the efficacy of all available
home-based non-pharmacological treatments of depression. DESIGN: Systematic
review and network meta-analysis of randomised controlled trials. DATA SOURCES:
Medline, Scopus and Cumulative Index to Nursing and Allied Health Literature
(CINAHL) databases were searched since inceptions to 7 August 2016. ELIGIBILITY
CRITERIA: Randomised controlled trials comparing the efficacy of home-based non
pharmacological interventions with usual care of patients with depression were
included in the review. MAIN OUTCOMES: Depression symptom scores and disease
remission rates at the end of treatment. RESULTS: Seventeen studies were included
in the review. Home-based non-pharmacological interventions were categorised as
(1) home-based psychological intervention, (2) home-based exercise intervention,
(3) combined home-based psychological intervention with exercise intervention and
(4) complementary medicine. Complementary medicine approaches were excluded from
the meta-analysis due to heterogeneity. The standardised mean differences of post
treatment depression symptom scores between usual care groups and home-based
psychological intervention, home-based exercise intervention and combined home
based psychological intervention with exercise intervention were a^'0.57 (95% CI
a^'0.84 to a^'0.31), a^'1.03 (95% CI a^'2.89 to 0.82) and a^'0.78 (95% CI a^'1.09
to a^'0.47), respectively. These results suggest that only home-based
psychological intervention and combined home-based psychological intervention
with exercise intervention could significantly decrease depression scores.
Compared with usual care groups, the disease remission rate was also
significantly higher for home-based psychological intervention (pooled risk
ratio=1.53; 95%a?0/00CI 1.19 to 1.98) and combined home-based psychological
intervention with exercise intervention (pooled risk ratio=3.47; 95%a?0/00CI 2.11
to 5.70). Of all the studied interventions, combined home-based psychological
intervention with exercise intervention had the highest probability of resulting
in disease remission. CONCLUSION: Our study confirms the efficacy of home-based
psychological intervention and combined home-based psychological intervention
with exercise intervention in the treatment of depression. Combined home-based
psychological intervention and exercise intervention was the best treatment and
should be considered for inclusion in clinical guidelines for managing
depression.
PMID- 28706087
TI - Periconception endogenous and exogenous maternal sex steroid hormones and risk of
asthma and allergy in offspring: protocol for a systematic review and meta
analysis.
AB - INTRODUCTION: Pregnancy is associated with several hormonal changes which
influence the developing fetus. Variations in maternal endogenous hormones and
prepregnancy use of hormonal preparations have been linked to asthma and allergy
in the offspring, but findings are inconsistent. We plan to undertake a
systematic review to synthesise the evidence on the association between
endogenous and exogenous maternal sex hormones and the risk of asthma and allergy
in the offspring. METHODS AND ANALYSIS: We will search Medline, Embase, Cochrane
Library, Institute of Scientific Information Web of Science, Cumulative Index of
Nursing and Allied Health, Scopus, Google Scholar, Allied and Complementary
Medicine Database, Global Health, Psychological Information (PsycINFO), Centre
for Agriculture and Bioscience (CAB) International and WHO Global Health Library
from inception until 2016 to identify relevant studies on the topic. Additional
studies will be identified by searching databases of proceedings of international
conferences, contacting international experts in the field and searching the
references cited in identified studies. We will include analytical
epidemiological studies. Two researchers will independently screen identified
studies, undertake data extraction and assess risk of bias in eligible studies,
while a third reviewer will arbitrate any disagreement. We will use the Effective
Public Health Practice Project tool to assess the risk of bias in the studies. We
will perform a random-effects meta-analysis to synthesise the evidence. We will
use the Grading of Recommendations Assessment, Development and Evaluation
approach to rate the strength and quality of the overall evidence with respect to
each outcome. ETHICS AND DISSEMINATION: Ethical approval is not required since
the study is a systematic review of published literature. Our findings will be
reported in a peer-reviewed scientific journal. PROSPERO REGISTRATION NUMBER:
CRD42016048324.
PMID- 28706088
TI - Evaluating the importance of policy amenable factors in explaining influenza
vaccination: a cross-sectional multinational study.
AB - OBJECTIVES: Despite continuous efforts to improve influenza vaccination coverage,
uptake among high-risk groups remains suboptimal. We aimed to identify policy
amenable factors associated with vaccination and to measure their importance in
order to assist in the monitoring of vaccination sentiment and the design of
communication strategies and interventions to improve vaccination rates. SETTING:
The USA, the UK and France. PARTICIPANTS: A total of 2412 participants were
surveyed across the three countries. OUTCOME MEASURES: Self-reported influenza
vaccination. METHODS: Between March and April 2014, a stratified random sampling
strategy was employed with the aim of obtaining nationally representative samples
in the USA, the UK and France through online databases and random-digit dialling.
Participants were asked about vaccination practices, perceptions and feelings.
Multivariable logistic regression was used to identify factors associated with
past influenza vaccination. RESULTS: The models were able to explain 64%-80% of
the variance in vaccination behaviour. Overall, sociopsychological variables,
which are inherently amenable to policy, were better at explaining past
vaccination behaviour than demographic, socioeconomic and health variables.
Explanatory variables included social influence (physician), influenza and
vaccine risk perceptions and traumatic childhood experiences. CONCLUSIONS: Our
results indicate that evidence-based sociopsychological items should be
considered for inclusion into national immunisation surveys to gauge the public's
views, identify emerging concerns and thus proactively and opportunely address
potential barriers and harness vaccination drivers.
PMID- 28706089
TI - Evaluation of the geriatric co-management for patients with fragility fractures
of the proximal femur (Geriatric Fracture Centre (GFC) concept): protocol for a
prospective multicentre cohort study.
AB - INTRODUCTION: Treatment of fractures in the elderly population is a clinical
challenge due partly to the presence of comorbidities. In a Geriatric Fracture
Centre (GFC), patients are co-managed by a geriatrician in an attempt to improve
clinical outcomes and reduce morbidity and mortality. Until now the beneficial
effect of orthogeriatric co-management has not been definitively proven. The
primary objective of this study is to determine the effect of GFC on predefined
major adverse events related to a hip fracture compared to usual care centres
(UCC). The secondary objectives include assessments in quality of life, patient
reported outcomes and cost-effectiveness. METHODS AND ANALYSIS: Two hundred and
sixty-six elderly patients diagnosedwith hip fracture and planned to be treated
with osteosynthesis or endoprosthesis in either a GFC or UCC study site will be
recruited, 133 per type of centre. All procedures and management will be done
according to the site's standard of care. Study-related visits will be performed
at the following time points: preoperative, intraoperative, discharge from the
orthopaedic/trauma department, discharge to definite residential status, 12 weeks
and 12 months postsurgery. Data collected include demographics, residential
status, adverse events, patient-reported outcomes, fall history, costs and
resources related to treatment. The risk of major adverse events at 12 months
will be calculated for each centre type; patient-reported outcomes will be
analysed by mixed effects regression models to estimate differences in mean
scores between baseline and follow-ups whereas cost-effectiveness will be
assessed using the incremental cost-effectiveness ratio. ETHICS AND
DISSEMINATION: Ethics approval for this study was granted from the local Ethics
Committees or Institutional Review Board from each of the participating sites
prior to patient enrolment. The results of this study will be published in peer
reviewed journals and presented at different conferences. TRIAL REGISTRATION
NUMBER: ClinicalTrials.gov: NCT02297581; pre-results.
PMID- 28706090
TI - Improving site selection in clinical studies: a standardised, objective,
multistep method and first experience results.
AB - INTRODUCTION: A considerable number of clinical studies experience delays, which
result in increased duration and costs. In multicentre studies, patient
recruitment is among the leading causes of delays. Poor site selection can result
in low recruitment and bad data quality. Site selection is therefore crucial for
study quality and completion, but currently no specific guidelines are available.
MATERIAL AND METHODS: Selection of sites adequate to participate in a prospective
multicentre cohort study was performed through an open call using a newly
developed objective multistep approach. The method is based on use of a network,
definition of objective criteria and a systematic screening process. ILLUSTRATIVE
EXAMPLE OF THE METHOD AT WORK: Out of 266 interested sites, 24 were shortlisted
and finally 12 sites were selected to participate in the study. The steps in the
process included an open call through a network, use of selection questionnaires
tailored to the study, evaluation of responses using objective criteria and
scripted telephone interviews. At each step, the number of candidate sites was
quickly reduced leaving only the most promising candidates. Recruitment and
quality of data went according to expectations in spite of the contracting
problems faced with some sites. CONCLUSION: The results of our first experience
with a standardised and objective method of site selection are encouraging. The
site selection method described here can serve as a guideline for other
researchers performing multicentre studies. TRIAL REGISTRATION NUMBER:
ClinicalTrials.gov: NCT02297581.
PMID- 28706092
TI - Development of an intervention to support patients and clinicians with advanced
lung cancer when considering systematic anticancer therapy: protocol for the PACT
study.
AB - INTRODUCTION: Patient-centred care is essential to the delivery of healthcare;
however, this necessitates direct patient involvement in clinical decision-making
and can be challenging for patients diagnosed with advanced non-small cell lung
cancer where there may be misunderstanding of the extent of disease, prognosis
and aims of treatment. In this context, decisions are complex and there is a need
to balance the risks and benefits, including treatment with palliative intent.
The aim of the PACT study is to identify the information and decision support
needs of patients, leading to the development of an intervention to support
patients with advanced lung cancer when considering treatment options. METHODS
AND ANALYSIS: PACT is a five-stage, multimethod and multicentre study.
Participants: Patients and health professionals will be recruited from three
health boards. Methods: Non-participant observation of multidisciplinary team
meetings (n=12) will be used to determine patients' allocation to treatment
pathways (stage I). Non-participant observation of patient-clinician
consultations (n=20-30) will be used to explore communication of treatment
options and decision-making. Extent of participation in decision-making will be
assessed using the Observing Patient Involvement in Shared Decision-Making tool.
Interviews with patients (stage III) and their clinicians (stage IV) will explore
the perception of treatment options and involvement in decision-making. Based on
stages I-IV, an expert consensus meeting will finalise the content and format of
the intervention. Cognitive interviews with patients will then determine the face
validity of the intervention (stage V). Analysis: analysis will be according to
data type and research question and will include mediated discourse analysis,
thematic analysis, framework analysis and interpretative phenomenological
analysis. ETHICS AND DISSEMINATION: Ethical approval has been granted. The study
findings will contribute to and promote shared and informed decision-making in
the best interest of patients and prudent healthcare. We therefore aim to
disseminate results via relevant respiratory, oncology and palliative care
journals and conferences.
PMID- 28706091
TI - PREDICT-CP: study protocol of implementation of comprehensive surveillance to
predict outcomes for school-aged children with cerebral palsy.
AB - OBJECTIVES: Cerebral palsy (CP) remains the world's most common childhood
physical disability with total annual costs of care and lost well-being of
$A3.87b. The PREDICT-CP (NHMRC 1077257 Partnership Project: Comprehensive
surveillance to PREDICT outcomes for school age children with CP) study will
investigate the influence of brain structure, body composition, dietary intake,
oropharyngeal function, habitual physical activity, musculoskeletal development
(hip status, bone health) and muscle performance on motor attainment, cognition,
executive function, communication, participation, quality of life and related
health resource use costs. The PREDICT-CP cohort provides further follow-up at 8
12 years of two overlapping preschool-age cohorts examined from 1.5 to 5 years
(NHMRC 465128 motor and brain development; NHMRC 569605 growth, nutrition and
physical activity). METHODS AND ANALYSES: This population-based cohort study
undertakes state-wide surveillance of 245 children with CP born in Queensland
(birth years 2006-2009). Children will be classified for Gross Motor Function
Classification System; Manual Ability Classification System, Communication
Function Classification System and Eating and Drinking Ability Classification
System. Outcomes include gross motor function, musculoskeletal development (hip
displacement, spasticity, muscle contracture), upper limb function, communication
difficulties, oropharyngeal dysphagia, dietary intake and body composition,
participation, parent-reported and child-reported quality of life and medical and
allied health resource use. These detailed phenotypical data will be compared
with brain macrostructure and microstructure using 3 Tesla MRI (3T MRI).
Relationships between brain lesion severity and outcomes will be analysed using
multilevel mixed-effects models. ETHICS AND DISSEMINATION: The PREDICT-CP
protocol is a prospectively registered and ethically accepted study protocol. The
study combines data at 1.5-5 then 8-12 years of direct clinical assessment to
enable prediction of outcomes and healthcare needs essential for tailoring
interventions (eg, rehabilitation, orthopaedic surgery and nutritional
supplements) and the projected healthcare utilisation. TRIAL REGISTRATION NUMBER:
ACTRN: 12616001488493.
PMID- 28706093
TI - Does neutrophil-to-lymphocyte ratio predict 1-year mortality in patients with
primary biliary cholangitis? Results from a retrospective study with validation
cohort.
AB - OBJECTIVES: Neutrophil-to-lymphocyte ratio (NLR) has been used to predict
prognosis in various liver diseases, but its role in primary biliary cholangitis
(PBC) is not clarified. We aimed to investigate the prognostic usefulness of NLR
for 1-year mortality in PBC. METHODS: The study recruited a retrospective cohort
with 88 patients with PBC and a prospective validation cohort with 63
participants who were followed-up for 1 year. NLR and other laboratory
measurements were analysed by multivariate regression model for identifying
independent factors for early mortality. The cut-off threshold of NLR was
determined by calculating the area under the receiver operating characteristics
curve (AUROC) and used in a subsequent Kaplan-Meier survival analysis. RESULTS:
Univariate and multivariate analyses showed that Mayo Risk Score (MRS), serum
creatinine and NLR were independent indicators for mortality. NLR yielded
significantly higher AUROC (0.86) than those of platelet-to-lymphocyte ratio
(0.58, p=0.03), but comparable with MRS (0.87, p=0.88). Spearman's correlation
analysis represented a positive correlation between escalating NLR and
aggravating Child-Pugh grade (r=0.44, p<0.001). Patients with NLR <2.18 exhibited
higher survival (with 100% sensitivity and 67.1% specificity) within 1 year
follow-up duration, and NLR >=2.18 was indicative of higher mortality (log-rank
test, p<0.001). In addition, these results were internally confirmed by a
validation cohort. CONCLUSION: NLR is closely related to short-term mortality in
patients with PBC.
PMID- 28706094
TI - Ventilatory function as a predictor of mortality in lifelong non-smokers:
evidence from large British cohort studies.
AB - BACKGROUND: Reduced ventilatory function is an established predictor of all-cause
mortality in general population cohorts. We sought to verify this in lifelong non
smokers, among whom confounding by active smoking can be excluded, and
investigate associations with circulatory and cancer deaths. METHODS: In UK
Biobank, among 149 343 white never-smokers aged 40-69 years at entry, 2401 deaths
occurred over a mean of 6.5-year follow-up. In the Health Surveys for England
(HSE) 1995, 1996, 2001 and Scottish Health Surveys (SHS) 1998 and 2003 combined,
there were 500 deaths among 6579 white never-smokers aged 40-69 years at entry,
followed for a mean of 13.9 years. SD (z) scores for forced expiratory volume in
the first second (FEV1) and forced vital capacity (FVC) were derived using Global
Lung Initiative 2012 reference equations. These z-scores were related to deaths
from all causes, circulatory disease and cancers using proportional hazards
models adjusted for age, sex, height, socioeconomic status, region and survey.
RESULTS: In the HSE-SHS data set, decreasing z-scores for FEV1 (zFEV1) and FVC
(zFVC) were each associated to a similar degree with increased all-cause
mortality (hazard ratios per unit decrement 1.17, 95% CI 1.09 to 1.25 for zFEV1
and 1.19, 95% CI 1.10 to 1.28 for zFVC). This was replicated in Biobank (HRs
1.21, 95% CI 1.17 to 1.26 and 1.24, 1.19 to 1.29, respectively). zFEV1 and zFVC
were less strongly associated with mortality from circulatory diseases in HSE-SHS
(HR 1.22, 95% CI 1.06 to 1.40 for zFVC) than in Biobank (HR 1.47, 95% CI 1.35 to
1.60 for zFVC). For cancer mortality, HRs were more consistent between cohorts
(for zFVC: HRs 1.12, 95% CI 1.01 to 1.24 in HSE-SHS and 1.10, 1.05 to 1.15 in
Biobank). The strongest associations were with respiratory mortality (for zFVC:
HRs 1.61, 95% CI 1.25 to 2.08 in HSE-SHS and 2.15, 1.77 to 2.61 in Biobank).
CONCLUSIONS: Spirometric indices predicted mortality more strongly than systolic
blood pressure or body mass index, emphasising the importance of promoting lung
health in the general population, even among lifelong non-smokers.
PMID- 28706095
TI - Elucidating the information exchange during interfacility care transitions:
Insights from a Qualitative Study.
AB - OBJECTIVE: To explore the perceptions of patients, their caregivers and
healthcare professionals associated with the exchange of information during
transitioning from two acute care hospitals to one rehabilitation hospital.
DESIGN: An exploratory qualitative study using semi-structured interviews and
observation. PARTICIPANTS AND SETTING: Patients over the age of 65 years admitted
to an orthopaedic unit for a non-elective admission, their caregivers and
healthcare professionals involved in their care. Participating sites included
orthopaedic inpatient units from two acute care teaching hospitals and one
orthopaedic unit at a rehabilitation hospital in an urban setting. FINDINGS:
Three distinct themes emerged from participants' narrative of their transitional
care experience: (1) having no clue what the care plan is, (2) being told and
notified about the plan and (3) experiencing challenges absorbing information.
Participating patients and their caregivers reported not being engaged in an
active discussion with healthcare professionals about their care transition plan.
Several healthcare professionals described withholding information within the
plan until they themselves were clear about the transition outcomes. CONCLUSION:
This study highlights the need to increase efforts to ensure that effective
information exchanges occur during transition from acute care hospital to
rehabilitation settings.
PMID- 28706096
TI - Measuring patient safety culture in maternal and child health institutions in
China: a qualitative study.
AB - INTRODUCTION: Patient safety culture (PSC) plays a critical role in ensuring safe
and quality care. Extensive PSC studies have been undertaken in hospitals.
However, little is known about PSC in maternal and child health (MCH)
institutions in China, which provide both population-based preventive services as
well as individual care for patients. OBJECTIVES: This study aimed to develop a
theoretical framework for conceptualising PSC in MCH institutions in China.
METHODS: The study was undertaken in six MCH institutions (three in Hebei and
three in Beijing). Participants (n=118) were recruited through stratified
purposive sampling: 20 managers/administrators, 59 care providers and 39
patients. In-depth interviews were conducted with the participants. The interview
data were coded using both inductive (based on the existing PSC theory developed
by the Agency for Healthcare Research and Quality) and deductive (open coding
arising from data) approaches. A PSC framework was formulated through axial
coding that connected initial codes and selective coding that extracted a small
number of themes. RESULTS: The interviewees considered patient safety in relation
to six aspects: safety and security in public spaces, safety of medical services,
privacy and information security, financial security, psychological safety and
gap in services. A 12-dimensional PSC framework was developed, containing 69
items. While the existing PSC theory was confirmed by this study, some new themes
emerged from the data. Patients expressed particular concerns about psychological
safety and financial security. Defensive medical practices emerged as a PSC
dimension that is associated with not only medical safety but also financial
security and psychological safety. Patient engagement was also valued by the
interviewees, especially the patients, as part of PSC. CONCLUSIONS: Although
there are some common features in PSC across different healthcare delivery
systems, PSC can also be context specific. In MCH settings in China, the meaning
of 'patient safety' goes beyond the traditional definition of patients. General
well-being, health and disease prevention are important anchor points for
defining PSC in such settings.
PMID- 28706097
TI - Changes in psychosocial and physical working conditions and psychotropic
medication in ageing public sector employees: a record-linkage follow-up study.
AB - OBJECTIVES: To investigate whether changes in psychosocial and physical working
conditions are associated with subsequent psychotropic medication in ageing
employees. METHODS: Data were from the Helsinki Health Study, a cohort study of
Finnish municipal employees, aged 40-60 years at phase 1 (2000-2002). Changes in
psychosocial and physical working conditions were measured between phase 1 and
phase 2 (2007). Survey data were longitudinally linked to data on prescribed,
reimbursed psychotropic medication purchases (Anatomical Therapeutic Chemical)
obtained from the registers of the Social Insurance Institution of Finland
between the phase 2 survey and December 2013 (N=3587; 80% women). Outcomes were
any psychotropic medication; antidepressants (N06A); anxiolytics (N05B); and
sedatives and hypnotics (N05C). Cox regression analyses were performed. RESULTS:
During the follow-up, 28% of the participants were prescribed psychotropic
medication. Repeated exposures to low job control, high job demands and high
physical work load were associated with an increased risk of subsequent
antidepressant and anxiolytic medication. Increased and repeated exposure to high
physical work load, increased job control and repeated high job demands were
associated with subsequent sedative and hypnotic medication. Age and sex-adjusted
HR varied from 1.18 to 1.66. Improvement in job control was associated with a
lower risk of anxiolytic, but with a higher risk of sedatives and hypnotic
medication. Decreased physical work load was associated with a lower risk of
antidepressant and anxiolytic medications. CONCLUSION: Improvement in working
conditions could lower the risk of mental ill-health indicated by psychotropic
medication.
PMID- 28706098
TI - Changes in hypertension prevalence, awareness, treatment and control rates over
20 years in National Capital Region of India: results from a repeat cross
sectional study.
AB - BACKGROUND AND OBJECTIVES: Despite being one of the leading risk factors of
cardiovascular mortality, there are limited data on changes in hypertension
burden and management from India. This study evaluates trend in the prevalence,
awareness, treatment and control of hypertension in the urban and rural areas of
India's National Capital Region (NCR). DESIGN AND SETTING: Two representative
cross-sectional surveys were conducted in urban and rural areas (survey 1 (1991
1994); survey 2 (2010-2012)) of NCR using similar methodologies. PARTICIPANTS: A
total of 3048 (mean age: 46.8+/-9.0 years; 52.3% women) and 2052 (mean age:
46.5+/-8.4 years; 54.2% women) subjects of urban areas and 2487 (mean age: 46.6+/
8.8 years; 57.0% women) and 1917 (mean age: 46.5+/-8.5 years; 51.3% women)
subjects of rural areas were included in survey 1 and survey 2, respectively.
PRIMARY AND SECONDARY OUTCOME MEASURES: Hypertension was defined as per Joint
National Committee VII guidelines. Structured questionnaire was used to measure
the awareness and treatment status of hypertension. A mean systolic blood
pressure <140 mm Hg and diastolic blood pressure <90 mm Hg was defined as control
of hypertension among the participants with hypertension. RESULTS: The age and
sex standardised prevalence of hypertension increased from 23.0% to 42.2%
(p<0.001) and 11.2% to 28.9% (p<0.001) in urban and rural NCR, respectively. In
both surveys, those with high education, alcohol use, obesity and high fasting
blood glucose were at a higher risk for hypertension. However, the change in
hypertension prevalence between the surveys was independent of these risk factors
(adjusted OR (95% CI): urban (2.3 (2.0 to 2.7)) rural (3.1 (2.4 to 4.0))).
Overall, there was no improvement in awareness, treatment and control rates of
hypertension in the population. CONCLUSION: There was marked increase in
prevalence of hypertension over two decades with no improvement in management.
PMID- 28706099
TI - Cross-sectional study of the hospital management of adult patients with a
suspected seizure (EPIC2).
AB - OBJECTIVE: To determine the clinical characteristics, management and outcomes of
patients taken to hospital by emergency ambulance after a suspected seizure.
DESIGN: Quantitative cross-sectional retrospective study of a consecutive series
of patients. SETTING: An acute hospital trust in a large city in England.
PARTICIPANTS: In 2012-2013, the regions' ambulance service managed 605 481
emergency incidents, 74 141/605 481 originated from Sheffield (a large city in
the region), 2121/74 141 (2.9%) were suspected seizures and 178/2121 occurred in
May 2012. We undertook detailed analysis of the medical records of the 91/178
patients who were transported to the city's acute hospital. After undertaking a
retrospective review of the medical records, the best available aetiological
explanation for the seizures was determined. RESULTS: The best available
aetiological explanation for 74.7% (68/91) of the incidents was an epileptic
seizure, 11.0% (10/91) were psychogenic non-epileptic seizures and 9.9% (9/91)
were cardiogenic events. The epileptic seizures fall into the following four
categories: first epileptic seizure (13.2%, 12/91), epileptic seizure with a
historical diagnosis of epilepsy (30.8%, 28/91), recurrent epileptic seizures
without a historical diagnosis of epilepsy (20.9%, 19/91) and acute symptomatic
seizures (9.9%, 9/91). Of those with seizures (excluding cardiogenic events),
2.4% (2/82) of patients were seizing on arrival in the Emergency Department (ED),
19.5% (16/82) were postictal and 69.5% (57/82) were alert. 63.4% (52/82) were
discharged at the end of their ED attendance and 36.5% (19/52) of these had no
referral or follow-up. CONCLUSIONS: Most suspected seizures are epileptic
seizures but this is a diagnostically heterogeneous group. Only a small minority
of patients require emergency medical care but most are transported to hospital.
Few patients receive expert review and many are discharged home without referral
to a specialist leaving them at risk of further seizures and the associated
morbidity, mortality and health services costs of poorly controlled epilepsy.
PMID- 28706100
TI - Medical service use and usual care of common shoulder disorders in Korea: a cross
sectional study using the Health Insurance Review and Assessment Service National
Patient Sample.
AB - OBJECTIVES: This study examined National Health Insurance claims data to
investigate the epidemiology of shoulder disorders in Korea. Detailed information
on medical services and related costs was assessed by major shoulder disorder
category. DESIGN AND SETTING: The 2014 National Patient Sample dataset provided
by the Health Insurance Review and Assessment Service was analysed. Among
shoulder-related diagnosis codes, adhesive capsulitis of the shoulder (ACS),
rotator cuff syndrome (RCS) and shoulder impingement syndrome (SIS) categories
were of highest prevalence. Sociodemographic characteristics and medical service
use, frequency and medical costs regarding common shoulder disorders were
evaluated. RESULTS: The majority of patients with shoulder disorder received
ambulatory care (97%). Total and per-patient expenses were highest in patients
with RCS. The number of inpatients with RCS was more than twice that of the other
two groups, and patients with RCS were more likely to receive surgical management
compared with patients with ACS and SIS. Prevalence of shoulder disorders was
highest among subjects in their 50s for all three groups. Primary care physicians
treated 75.80% of patients with ACS, 56.99% of patients with RCS and 48.06% of
patients with SIS, respectively, outlining the difference in medical institution
usage patterns. In all three groups, the highest proportion of patients visited
orthopaedic surgeons out of medical departments. In the ACS and SIS groups, cost
of visits (consultations) took up the largest part of total expenses at 32.30%
and 18.88%, respectively, while cost of procedure/surgery constituted the largest
portion in patients with RCS (37.77%). The usage proportion of subcutaneous or
intramuscular and intra-articular injections ranged between 20% and 30% for
outpatients in all three groups. CONCLUSIONS: Medical service use, frequency and
cost distributions relating to major shoulder disorders in Korea were assessed
using nationwide claims data. These findings are expected to aid policy-makers as
well as researchers and practitioners as basic healthcare data.
PMID- 28706101
TI - Low-value clinical practices in injury care: a scoping review protocol.
AB - INTRODUCTION: Preventable injuries lead to 200 000 hospital stays, 60 000
disabilities, and 13 000 deaths per year in Canada with direct costs of $20
billion. Overall, potentially unnecessary medical interventions are estimated to
consume up to 30% of healthcare resources and may expose patients to avoidable
harm. However, little is known about overuse for acute injury care. We aim to
identify low-value clinical practices in injury care. METHODS AND ANALYSIS: We
will perform a scoping review of peer-reviewed and non-peer-reviewed literature
to identify research articles, reviews, recommendations and guidelines that
identify at least one low-value clinical practice specific to injury populations.
We will search Medline, EMBASE, COCHRANE central, and BIOSIS/Web of Knowledge
databases, websites of government agencies, professional societies and patient
advocacy organisations, thesis holdings and conference proceedings. Pairs of
independent reviewers will evaluate studies for eligibility and extract data from
included articles using a prepiloted and standardised electronic data abstraction
form. Low-value clinical practices will be categorised using an extension of the
Agency for Healthcare Research and Quality conceptual framework and data will be
presented using narrative synthesis. ETHICS AND DISSEMINATION: Ethics approval is
not required as original data will not be collected. This study will be
disseminated in a peer-reviewed journal, international scientific meetings, and
to knowledge users through clinical and healthcare quality associations. This
review will contribute new knowledge on low-value clinical practices in acute
injury care. Our results will support the development indicators to measure
resource overuse and inform policy makers on potential targets for deadoption in
injury care.
PMID- 28706102
TI - A method to assess obstetric outcomes using the 10-Group Classification System: a
quantitative descriptive study.
AB - OBJECTIVES: Internationally, the 10-Group Classification System (TGCS) has been
used to report caesarean section rates, but analysis of other outcomes is also
recommended. We now aim to present the TGCS as a method to assess outcomes of
labour and delivery using routine collection of perinatal information. DESIGN:
This research is a methodological study to describe the use of the TGCS. SETTING:
Stavanger University Hospital (SUH), Norway, National Maternity Hospital Dublin,
Ireland and Slovenian National Perinatal Database (SLO), Slovenia. PARTICIPANTS:
9848 women from SUH, Norway, 9250 women from National Maternity Hospital Dublin,
Ireland and 106 167 women, from SLO, Slovenia. MAIN OUTCOME MEASURES: All women
were classified according to the TGCS within which caesarean section, oxytocin
augmentation, epidural analgesia, operative vaginal deliveries, episiotomy,
sphincter rupture, postpartum haemorrhage, blood transfusion, maternal age >35
years, body mass index >30, Apgar score, umbilical cord pH, hypoxic-ischaemic
encephalopathy, antepartum and perinatal deaths were incorporated. RESULTS: There
were significant differences in the sizes of the groups of women and the
incidences of events and outcomes within the TGCS between the three perinatal
databases. CONCLUSIONS: The TGCS is a standardised objective classification
system where events and outcomes of labour and delivery can be incorporated.
Obstetric core events and outcomes should be agreed and defined to set standards
of care. This method provides continuous and available observations from delivery
wards, possibly used for further interpretation, questions and international
comparisons. The definition of quality may vary in different units and can only
be ascertained when all the necessary information is available and considered
together.
PMID- 28706103
TI - Vitamin D levels in critically ill patients with acute kidney injury: a protocol
for a prospective cohort study (VID-AKI).
AB - INTRODUCTION: Acute kidney injury (AKI) affects more than 50% of critically ill
patients. The formation of calcitriol, the active vitamin D metabolite, from the
main inactive circulating form, 25-hydroxyvitamin D (25(OH)D), occurs primarily
in the proximal renal tubules. This results in a theoretical basis for reduction
in levels of calcitriol over the course of an AKI. Vitamin D deficiency is highly
prevalent in critically ill adults, and has been associated with increased rates
of sepsis, longer hospital stays and increased mortality. The primary objective
of this study is to perform serial measurements of 25(OH)D and calcitriol
(1,25(OH)2D), as well as parathyroid hormone (PTH) and fibroblast growth factor
23 (FGF23) levels, in critically ill adult patients with and without AKI, and to
determine whether patients with AKI have significantly lower vitamin D metabolite
concentrations. The secondary objectives are to describe dynamic changes in
vitamin D metabolites, PTH and FGF23 during critical illness; to compare vitamin
D metabolite concentrations in patients with AKI with and without renal
replacement therapy; and to investigate whether there is an association between
vitamin D status and outcomes. METHODS AND ANALYSIS: 230 general adult intensive
care patients will be recruited. The AKI arm will include 115 critically ill
patients with AKI Kidney Disease Improving Global Outcome stage II or stage III.
The comparison group will include 115 patients who require cardiovascular or
respiratory support, but who do not have AKI. Serial measurements of vitamin D
metabolites and associated hormones will be taken on prespecified days. Patients
will be recruited from two large teaching Trusts in England. Data will be
analysed using standard statistical methods. ETHICS AND DISSEMINATION: Ethical
approval was obtained. Upon completion, the study team will submit the study
report for publication in a peer-reviewed scientific journal and for conference
presentation. TRIAL REGISTRATION NUMBER: NCT02869919; Pre-results.
PMID- 28706104
TI - Use of a mobile social networking intervention for weight management: a mixed
methods study protocol.
AB - INTRODUCTION: Obesity and physical inactivity are major societal challenges and
significant contributors to the global burden of disease and healthcare costs.
Information and communication technologies are increasingly being used in
interventions to promote behaviour change in diet and physical activity. In
particular, social networking platforms seem promising for the delivery of weight
control interventions.We intend to pilot test an intervention involving the use
of a social networking mobile application and tracking devices (Fitbit Flex 2 and
Fitbit Aria scale) to promote the social comparison of weight and physical
activity, in order to evaluate whether mechanisms of social influence lead to
changes in those outcomes over the course of the study. METHODS AND ANALYSIS:
Mixed-methods study involving semi-structured interviews and a pre-post quasi
experimental pilot with one arm, where healthy participants in different body
mass index (BMI) categories, aged between 19 and 35 years old, will be subjected
to a social networking intervention over a 6-month period. The primary outcome is
the average difference in weight before and after the intervention. Secondary
outcomes include BMI, number of steps per day, engagement with the intervention,
social support and system usability. Semi-structured interviews will assess
participants' expectations and perceptions regarding the intervention. ETHICS AND
DISSEMINATION: Ethics approval was granted by Macquarie University's Human
Research Ethics Committee for Medical Sciences on 3 November 2016 (ethics
reference number 5201600716).The social network will be moderated by a researcher
with clinical expertise, who will monitor and respond to concerns raised by
participants. Monitoring will involve daily observation of measures collected by
the fitness tracker and the wireless scale, as well as continuous supervision of
forum interactions and posts. Additionally, a protocol is in place to monitor for
participant misbehaviour and direct participants-in-need to appropriate sources
of help.
PMID- 28706105
TI - How people with dementia and carers understand and react to social functioning
changes in mild dementia: a UK-based qualitative study.
AB - OBJECTIVES: To analyse people with dementia and their family carers' attribution
of social changes in dementia and the consequences of these attributions. DESIGN:
Qualitative study, using a semi-structured interview guide. Individual interviews
continued to theoretical saturation. Two researchers independently analysed
interview transcripts. SETTING AND PARTICIPANTS: People with mild dementia and
family carers purposively selected from London-based memory services for diverse
demographic characteristics to encompass a range of experiences. PRIMARY AND
SECONDARY OUTCOMES: Attribution of social changes experienced by the person with
dementia and the consequences of these attributions. RESULTS: We interviewed nine
people with dementia and nine carers, encompassing a range of age, ethnicity and
educational backgrounds.Both groups reported that the person with dementia had
changed socially. People with dementia tended to give one or two explanations for
social change, but carers usually suggested several. People with dementia were
often socially embarrassed or less interested in going out, and they or their
relatives' physical illness or fear of falls led to reduced social activity.
Carers often attributed not going out to a choice or premorbid personality.
Carers found that their relative needed more support to go out than they could
give and carers needed time to themselves because of carer stress or other
problems from which they shielded the person with dementia. Additionally, there
was decreased opportunity to socialise, as people were bereaved of friends and
family. Participants acknowledged the direct impact of dementia symptoms on their
ability to socially engage but sometimes decided to give up socialising when they
knew they had dementia. There were negative consequences from social changes
being attributed to factors such as choice, rather than dementia. CONCLUSION:
Clinicians should ask about social changes in people with dementia. Explaining
that these may be due to dementia and considering strategies to overcome them may
be beneficial.
PMID- 28706106
TI - Detailed assessment of benefits and risks of retrievable inferior vena cava
filters on patients with complicated injuries: the da Vinci multicentre
randomised controlled trial study protocol.
AB - INTRODUCTION: Retrievable inferior vena cava (IVC) filters have been increasingly
used in patients with major trauma who have contraindications to anticoagulant
prophylaxis as a primary prophylactic measure against venous thromboembolism
(VTE). The benefits, risks and cost-effectiveness of such strategy are uncertain.
METHODS AND ANALYSIS: Patients with major trauma, defined by an estimated Injury
Severity Score >15, who have contraindications to anticoagulant VTE prophylaxis
within 72 hours of hospitalisation to the study centre will be eligible for this
randomised multicentre controlled trial. After obtaining consent from patients,
or the persons responsible for the patients, study patients are randomly
allocated to either control or IVC filter, within 72 hours of trauma admission,
in a 1:1 ratio by permuted blocks stratified by study centre. The primary
outcomes are (1) the composite endpoint of (A) pulmonary embolism (PE) as
demonstrated by CT pulmonary angiography, high probability ventilation/perfusion
scan, transoesophageal echocardiography (by showing clots within pulmonary
arterial trunk), pulmonary angiography or postmortem examination during the same
hospitalisation or 90-day after trauma whichever is earlier and (B) hospital
mortality; and (2) the total cost of treatment including the costs of an IVC
filter, total number of CT and ultrasound scans required, length of intensive
care unit and hospital stay, procedures and drugs required to treat PE or
complications related to the IVC filters. The study started in June 2015 and the
final enrolment target is 240 patients. No interim analysis is planned; incidence
of fatal PE is used as safety stopping rule for the trial. ETHICS AND
DISSEMINATION: Ethics approval was obtained in all four participating centres in
Australia. Results of the main trial and each of the secondary endpoints will be
submitted for publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER:
ACTRN12614000963628; Pre-results.
PMID- 28706107
TI - Interventions that improve maternity care for immigrant women in the UK: protocol
for a narrative synthesis systematic review.
AB - INTRODUCTION: A quarter of all births in the UK are to mothers born outside the
UK. There is also evidence that immigrant women have higher maternal and infant
death rates and of inequalities in the provision and uptake of maternity
services/birth centres. The topic is of great significance to the National Health
Service because of directives that address inequalities and the changing patterns
of migration to the UK. Our main question for the systematic review is 'what
interventions exist that are specifically focused on improving maternity care for
immigrant women in the UK?' The primary objective of this synthesis is to
generate new interpretations of research evidence. Second, the synthesis will
provide substantive base to guide developments and implementation of maternity
services/birth centres which are acceptable and effective for immigrant women in
the UK. METHODS AND ANALYSIS: We are using a narrative synthesis (NS) approach to
identify, assess scientific quality and rigour, and synthesise empirical data
focused on access and interventions that enhance quality of maternity care/birth
centres for the UK immigrant women. The inclusion criteria include: publication
date 1990 to present, English language, empirical research and findings are
focused on women who live in the UK, participants of the study are immigrant
women, is related to maternity care/birth centres access or interventions or
experiences of maternity.In order to ensure the robustness of the NS, the
methodological quality of key evidence will be appraised using the Center for
Evidence-Based Management tools and review confidence with CERQual (Confidence in
the Evidence from Reviews of Qualitative Research). Two reviewers will
independently screen studies and extract relevant evidence. We will synthesise
evidence studying relationships between included studies using a range of tools.
DISSEMINATION: Dissemination plan includes: an e-workshop for policymakers,
collaborative practitioner workshops, YouTube video and APP, scientific papers
and conference presentations.
PMID- 28706108
TI - Novel function of a dynein light chain in actin assembly during clathrin-mediated
endocytosis.
AB - Clathrin- and actin-mediated endocytosis is essential in eukaryotic cells. In
this study, we demonstrate that Tda2 is a novel protein of the endocytic
machinery necessary for normal internalization of native cargo in yeast. Tda2 has
not been classified in any protein family. Unexpectedly, solving the crystal
structure of Tda2 revealed it belongs to the dynein light chain family. However,
Tda2 works independently of the dynein motor complex and microtubules. Tda2 forms
a tight complex with the polyproline motif-rich protein Aim21, which interacts
physically with the SH3 domain of the Arp2/3 complex regulator Bbc1. The Tda2
Aim21 complex localizes to endocytic sites in a Bbc1- and filamentous actin
dependent manner. Importantly, the Tda2-Aim21 complex interacts directly with and
facilitates the recruitment of actin-capping protein, revealing barbed-end
filament capping at endocytic sites to be a regulated event. Thus, we have
uncovered a new layer of regulation of the actin cytoskeleton by a member of a
conserved protein family that has not been previously associated with a function
in endocytosis.
PMID- 28706111
TI - Carphology.
PMID- 28706110
TI - ABN meeting 3-5 May 2017, Liverpool.
PMID- 28706112
TI - Workup for Perinatal Stroke Does Not Predict Recurrence.
AB - BACKGROUND AND PURPOSE: Perinatal stroke, including neonatal and presumed
perinatal presentation, represents the age in childhood in which stroke occurs
most frequently. The roles of thrombophilia, arteriopathy, and cardiac anomalies
in perinatal ischemic stroke are currently unclear. We took a uniform approach to
perinatal ischemic stroke evaluation to study these risk factors and their
association with recurrent stroke. METHODS: We reviewed records of perinatal
stroke patients evaluated from August 2008 to February 2016 at a single referral
center. Demographics, echocardiography, arterial imaging, and thrombophilia
testing were collected. Statistical analysis was performed using Fisher exact
test. RESULTS: Across 215 cases, the median follow-up was 3.17 years (1.49,
6.46). Females comprised 42.8% of cases. Age of presentation was neonatal (110,
51.2%) or presumed perinatal (105, 48.8%). The median age at diagnosis was 2.9
days (interquartile range, 2.0-9.9) for neonatal stroke and 12.9 months
(interquartile range, 8.7-32.8) for presumed perinatal stroke. Strokes were
classified as arterial (149, 69.3%), venous (60, 27.9%), both (4, 1.9%), or
uncertain (2, 0.9%) by consensus imaging review. Of the 215 cases, there were 6
(2.8%) recurrent ischemic cerebrovascular events. Abnormal thrombophilia testing
was not associated with recurrent stroke, except for a single patient with
combined antithrombin deficiency and protein C deficiency. After excluding venous
events, 155 patients were evaluated for arteriopathy and cardioembolic risk
factors; neither was associated with recurrent stroke. Positive family history of
thrombosis was not predictive of abnormal thrombophilia testing. CONCLUSIONS:
Thrombophilia, arteriopathy, or cardioembolic risk factors were not predictive of
recurrent events after perinatal stroke. Thrombophilia evaluation in perinatal
stroke should only rarely be considered.
PMID- 28706113
TI - PD-L1 (Programmed Death Ligand 1) Protects Against Experimental Intracerebral
Hemorrhage-Induced Brain Injury.
AB - BACKGROUND AND PURPOSE: Intracerebral hemorrhage (ICH) is a neurologically
destructive stroke, for which no valid treatment is available. This preclinical
study examined the therapeutic effect of PD-L1 (programmed death ligand 1), a B7
family member and a ligand for both PD-1 (programmed death 1) and B7-1 (CD80), in
a murine ICH model. METHODS: ICH was induced by injecting autologous blood into
252 male C57BL/6 and Rag1-/- mice. One hour later, ICH mice were randomly
assigned to receive an intraperitoneal injection of vehicle, PD-L1, or anti-PD-L1
antibody. Neurological function was assessed along with brain edema, brain
infiltration of immune cells, blood-brain barrier integrity, neuron death, and
mTOR (mammalian target of rapamycin) pathway products. RESULTS: PD-L1
significantly attenuated neurological deficits, reduced brain edema, and
decreased hemorrhage volume in ICH mice. PD-L1 specifically downsized the number
of brain-infiltrating CD4+ T cells and the percentages of Th1 and Th17 cells but
increased the percentages of Th2 and regulatory T cells. In the PD-L1-treated
group, we observed an amelioration of the inflammatory milieu, decreased cell
death, and enhanced blood-brain barrier integrity. PD-L1 also inhibited the mTOR
pathway. The administration of anti-PD-L1 antibody produced the opposite effects
to those of PD-L1 in ICH mice. CONCLUSIONS: PD-L1 provided protection from the
damaging consequences of ICH.
PMID- 28706114
TI - One-Year Incidence, Time Trends, and Predictors of Recurrent Ischemic Stroke in
Sweden From 1998 to 2010: An Observational Study.
AB - BACKGROUND AND PURPOSE: Recent data on the incidence, time trends, and predictors
of recurrent ischemic stroke are limited for unselected patient populations.
METHODS: Data for ischemic stroke patients were obtained from The Swedish Stroke
Register (Riksstroke) between 1998 and 2009 and merged with The Swedish National
Inpatient Register. A reference group of patients was created by Statistics
Sweden. The ischemic stroke patient cohort was divided into 4 time periods.
Recurrent ischemic stroke within 1 year was recorded until 2010. Kaplan-Meier and
Cox regression analyses were performed to study time trends and predictors of
ischemic stroke recurrence. RESULTS: Of 196 765 patients with ischemic stroke,
11.3% had a recurrent ischemic stroke within 1 year. The Kaplan-Meier estimates
of the 1-year cumulative incidence of recurrent ischemic stroke decreased from
15.0% in 1998 to 2001 to 12.0% in 2007 to 2010 in the stroke patient cohort while
the cumulative incidence of ischemic stroke decreased from 0.7% to 0.4% in the
reference population. Age >75 years, prior ischemic stroke or myocardial
infarction, atrial fibrillation without warfarin treatment, diabetes mellitus,
and treatment with beta-blockers or diuretics were associated with a higher risk
while warfarin treatment for atrial fibrillation, lipid-lowering medication, and
antithrombotic treatment (acetylsalicylic acid, dipyridamole) were associated
with a reduced risk of recurrent ischemic stroke. CONCLUSIONS: The risk of
recurrent ischemic stroke decreased from 1998 to 2010. Well-known risk factors
for stroke were associated with a higher risk of ischemic stroke recurrence;
whereas, secondary preventive medication was associated with a reduced risk,
emphasizing the importance of secondary preventive treatment.
PMID- 28706115
TI - Endovascular Thrombectomy and Stroke Physicians: Equity, Access, and Standards.
PMID- 28706116
TI - Training Standards in Neuroendovascular Surgery: Program Accreditation and
Practitioner Certification.
AB - BACKGROUND AND PURPOSE: Neuroendovascular surgery is a medical subspecialty that
uses minimally invasive catheter-based technology and radiological imaging to
diagnose and treat diseases of the central nervous system, head, neck, spine, and
their vasculature. To perform these procedures, the practitioner needs an
extensive knowledge of the anatomy of the nervous system, vasculature, and
pathological conditions that affect their physiology. A working knowledge of
radiation biology and safety is essential. Similarly, a sufficient volume of
clinical and interventional experience, first as a trainee and then as a
practitioner, is required so that these treatments can be delivered safely and
effectively. METHODS: This document has been prepared under the aegis of the
Society of Neurological Surgeons and its Committee for Advanced Subspecialty
Training in conjunction with the Joint Section of Cerebrovascular Surgery for the
American Association of Neurological Surgeons and Congress of Neurological
Surgeons, the Society of NeuroInterventional Surgery, and the Society of Vascular
and Interventional Neurology. RESULTS: The material herein outlines the
requirements for institutional accreditation of training programs in
neuroendovascular surgery, as well as those needed to obtain individual
subspecialty certification, as agreed on by Committee for Advanced Subspecialty
Training, the Society of Neurological Surgeons, and the aforementioned Societies.
This document also clarifies the pathway to certification through an advanced
practice track mechanism for those current practitioners of this subspecialty who
trained before Committee for Advanced Subspecialty Training standards were
formulated. CONCLUSIONS: Representing neuroendovascular surgery physicians from
neurosurgery, neuroradiology, and neurology, the above mentioned societies seek
to standardize neuroendovascular surgery training to ensure the highest quality
delivery of this subspecialty within the United States.
PMID- 28706117
TI - Age-Specific Sex Differences in Magnetic Resonance Imaging-Depicted Carotid
Intraplaque Hemorrhage.
AB - BACKGROUND AND PURPOSE: Stroke rates are higher in men compared with women in the
fourth through seventh decades of life, and higher rates may result from
differences in carotid intraplaque hemorrhage (IPH), an unstable atherosclerotic
plaque component. We report age-specific sex differences in the presence of
magnetic resonance imaging-depicted carotid IPH. METHODS: Patients (n=1115)
underwent magnetic resonance imaging for carotid IPH between 2005 and 2014. Low
grade carotid stenosis patients (n=906) without prior endarterectomy were
eligible for this cross-sectional study. RESULTS: Of the 906 patients included
(mean age+/-SD in years, 66.98+/-15.15), 63 (6.95%) had carotid IPH. In men and
women, carotid IPH was present in 11.43% (48 of 420) and 3.09% (15 of 486),
respectively (P<0.0001). Multivariable logistic regression analysis confirmed
greater odds of carotid IPH in men for all ages: 45 to 54 (odds ratio=45.45; 95%
confidence interval, 3.43-500), 55 to 64 years (odds ratio=21.74; 95% confidence
interval, 3.21-142.86), 65 to 74 years (odds ratio=10.42; 95% confidence
interval, 2.91-37.04), and >=75 years (odds ratio=5.00; 95% confidence interval,
2.31-10.75). Male sex modified the effect of age on the presence of carotid IPH
(beta=0.074; SE=0.036; P=0.0411). CONCLUSIONS: Men have greater age-specific odds
of magnetic resonance imaging-depicted carotid IPH compared with women. With
increasing age post-menopause, the odds of carotid IPH in women becomes closer to
that of men. Delayed onset of carotid IPH in women, an unstable plaque component,
may partly explain differential stroke rates between sexes, and further studies
are warranted.
PMID- 28706118
TI - Carotid Stenosis: Role of Plaque Morphology in Recurrent Stroke Risk.
PMID- 28706120
TI - Amartya Sen and the Organization of Endovascular Stroke Treatment.
PMID- 28706119
TI - Disparities and Trends in Door-to-Needle Time: The FL-PR CReSD Study (Florida
Puerto Rico Collaboration to Reduce Stroke Disparities).
AB - BACKGROUND AND PURPOSE: In the United States, about half of acute ischemic stroke
patients treated with tPA (tissue-type plasminogen activator) receive treatment
within 60 minutes of hospital arrival. We aimed to determine the proportion of
patients receiving tPA within 60 minutes (door-to-needle time [DTNT] <=60) and 45
minutes (DTNT <=45) of hospital arrival by race/ethnicity and sex and to identify
temporal trends in DTNT <=60 and DTNT <=45. METHODS: Among 65 654 acute ischemic
stroke admissions in the National Institute of Neurological Disorders and Stroke
funded FL-PR CReSD study (Florida-Puerto Rico Collaboration to Reduce Stroke
Disparities) from 2010 to 2015, we included 6181 intravenous tPA-treated cases
(9.4%). Generalized estimating equations were used to determine predictors of
DTNT <=60 and DTNT <=45. RESULTS: DTNT <=60 was achieved in 42% and DTNT <=45 in
18% of cases. After adjustment, women less likely received DTNT <=60 (odds ratio,
0.81; 95% confidence interval, 0.72-0.92) and DTNT <=45 (odds ratio, 0.73; 95%
confidence interval, 0.57-0.93). Compared with Whites, Blacks less likely had
DTNT <=45 during off hours (odds ratio, 0.68; 95% confidence interval, 0.47
0.98). Achievement of DTNT <=60 and DTNT <=45 was highest in South Florida (50%,
23%) and lowest in West Central Florida (28%, 11%). CONCLUSIONS: In the FL-PR
CReSD, achievement of DTNT <=60 and DTNT <=45 remains low. Compared with Whites,
Blacks less likely receive tPA treatment within 45 minutes during off hours.
Treatment within 60 and 45 minutes is lower in women compared with men and lowest
in West Central Florida compared with other Florida regions and Puerto Rico.
Further research is needed to identify reasons for delayed thrombolytic treatment
in women and Blacks and factors contributing to regional disparities in DTNT.
PMID- 28706121
TI - Coming to the United States for a Stroke Research Fellowship.
PMID- 28706122
TI - European Stroke Organizational Report.
PMID- 28706123
TI - Cerebral Microbleeds in Murine Amyloid Angiopathy: Natural Course and
Anticoagulant Effects.
AB - BACKGROUND AND PURPOSE: Cerebral microbleeds (CMBs) predispose patients to
intracerebral hemorrhage. Preclinical models to examine the effects of
antithrombotic treatments on the development of clinically overt intracerebral
hemorrhage are needed. We examined the natural course of CMB development and the
effects of long-term anticoagulation with warfarin or dabigatran on cerebral
micro- and macrohemorrhage in mice overexpressing the APP23 (amyloid precursor
protein). METHODS: Repeated susceptibility-weighted magnetic resonance imaging
was performed in APP23 mice at the age of 18 and 21 months, respectively. After
establishing stable long-term anticoagulation effects of warfarin and dabigatran
on number and total volume of CMBs, the outcome parameters were compared with
nonanticoagulated control. RESULTS: CMBs were equally located in lobar and deep
brain regions, and number and total volume of CMBs increased over time.
Anticoagulation with either warfarin or dabigatran did not increase CMBs in APP23
significantly. Mice treated with warfarin numerically had a higher mortality
(nonanticoagulated: 31%; dabigatran: 35% versus warfarin: 55%; P=0.21). In
postmortem brains of prematurely dying animals warfarin caused significantly more
frequently large intracerebral hemorrhage than control and dabigatran.
CONCLUSIONS: Anticoagulation with warfarin or dabigatran for 3 to 4 months does
not promote the formation of CMBs in aged APP23 mice. Nevertheless, warfarin but
not dabigatran is associated with a higher risk of extensive intracerebral
hemorrhage, suggesting that this model may allow preclinical safety evaluation of
antithrombotic therapies.
PMID- 28706124
TI - Rethinking Training and Distribution of Vascular Neurology Interventionists in
the Era of Thrombectomy.
PMID- 28706125
TI - A Meta-Analysis of Contemporary Lesion Modification Strategies During
Percutaneous Coronary Intervention in 244,795 Patients From 22 Studies.
AB - OBJECTIVES: Outcomes with use of lesion-modification strategies in the drug
eluting stent era have received limited study. METHODS: We conducted a meta
analysis of 22 studies published between 2004-2016 reporting outcomes after use
of rotational atherectomy, cutting-balloon, and scoring-balloon angioplasty.
RESULTS: In observational trials, acute luminal gain was higher after lesion
modification as compared with control (standardized mean difference, 0.23 mm; 95%
confidence interval [CI], 0.01-0.44; P=.04), with no difference in acute gain in
randomized studies. Compared with control, lesion modification was associated
with lower restenosis in randomized trials (odds ratio [OR], 0.64; 95% CI, 0.45
0.90; P=.01). Ninety-day incidence of major adverse cardiovascular event (MACE)
was higher after lesion modification in observational studies (OR, 1.39; 95% CI,
1.05-1.83; P=.02), but similar in randomized trials. Ninety-day incidence of
target-lesion or target-vessel revascularization (TLR-TVR) and myocardial
infarction (MI) was similar. Ninety-day incidence of death was higher after
lesion modification in observational studies (OR, 1.42; 95% CI, 1.04-1.95;
P=.03), but similar in randomized trials. At 1 year, the MACE rate was similar
for lesion modification compared with control in observational studies, but lower
after lesion modification in randomized trials (OR, 0.65; 95% CI, 0.48-0.88;
P<.01). TLR-TVR was higher with lesion modification in observational studies, but
lower in randomized trials (OR, 0.64; 95% CI, 0.46-0.88; P<.01). CONCLUSIONS:
While observational studies suggest a higher early MACE rate and more restenosis,
randomized trials show similar short-term and improved long-term outcomes with
pre-stenting lesion modification compared with control.
PMID- 28706126
TI - Transfemoral Transcatheter Aortic Valve-in-Valve Implantation for Aortic Valve
Bioprosthesis Failure With the Fully Repositionable and Retrievable Lotus Valve:
A Single-Center Experience.
AB - OBJECTIVE: To report a first case series of the Lotus valve (Boston Scientific)
for the treatment of surgical aortic bioprosthesis failure. BACKGROUND: Valve-in
valve (VIV) transcatheter aortic valve implantation (TAVI) is an established
management option for surgical aortic bioprosthesis failure. Although TAVI has
proven efficacious, complications relating to suboptimal valve implantation have
been reported in approximately 5% of patients. The Lotus valve is fully
repositionable and retrievable, and therefore enables complete assessment of
valve function prior to definitive deployment. However, data supporting its use
for this indication are limited. METHODS: Consecutive patients who underwent
transfemoral VIV-TAVI at John Radcliffe Hospital between January 2015 and
December 2016 were retrospectively analyzed. Procedural and 30-day outcomes were
reported in accordance with Valve Academic Research Consortium-2 (VARC-2)
definitions. RESULTS: Seven patients underwent VIV-TAVI with the Lotus valve.
Device success according to VARC-2 criteria was achieved in 6 of the 7 patients.
Following implantation, transvalvular hemodynamics were acceptable, with a mean
gradient of 11.9 +/- 6.6 mm Hg. All patients had mild or no residual aortic
regurgitation. Specifically, no patient required further valve-related
intervention, or suffered myocardial infarction, stroke, or acute kidney injury
stage 2 or 3. There were no deaths during the follow-up period. CONCLUSIONS:
Transfemoral VIV-TAVI for the treatment of surgical aortic bioprosthesis failure
with the Lotus device appears to be safe and is associated with no significant
residual aortic regurgitation, and offers favorable transvalvular hemodynamics at
30-day follow-up.
PMID- 28706127
TI - Percutaneous Mechanical Circulatory Support for Cardiac Disease: Temporal Trends
in Use and Complications Between 2009 and 2015.
AB - BACKGROUND: We present the indications for use, temporal trends, complications,
and 1-year clinical outcomes after single-access percutaneous mechanical
circulatory support device placement from years 2009-2015 at our institution.
METHODS AND RESULTS: Patients with an intraaortic balloon pump (IABP) or Impella
device placed in the catheterization suite between January 1, 2009 and December
31, 2015 were included. There were a total of 778 patients in this study. The
mean number of devices placed per year was 111. There was no statistically
significant trend in total number of devices placed overall, but the rate of
Impella placement declined over time (P=.02). There was a significant trend
toward less use before high-risk percutaneous coronary intervention (PCI)
(P=.04). The composite secondary endpoint occurred in 59.4% of patients, with no
significant difference between patients treated with an IABP or Impella (P=.66).
There were 37 device-related complications, which occurred more commonly with the
Impella (12.5%) than with the IABP (3.7%; P<.01). CONCLUSIONS: There was no
significant overall change in the total number of devices placed per year, but we
did observe a decreased use of Impella support. There was a significant decrease
in the utilization of percutaneous mechanical circulatory support prior to high
risk PCI, driven primarily by a decreased usage of the IABP. There were more
complications related to the Impella device vs the IABP, with no improvement in
the composite outcome.
PMID- 28706165
TI - [Illness Experience of Married Korean Women with Epilepsy].
AB - PURPOSE: The purpose of this study was to understand and describe the illness
experience of married Korean women with epilepsy. METHODS: Data were collected
during 2015~2016 through individual in-depth interviews with 12 married women
with epilepsy. Verbatim transcripts were analyzed using Giorgi's phenomenological
analysis to uncover the meaning of the illness experience of the participants.
RESULTS: The study results showed that the illness experience of married Korean
women with epilepsy was clustered into a specific description of situated
structure and a general description of situated structure. Six themes from 20
meaning units were identified: 1) Undermined self-esteem with stigma of being
epileptic; 2) Limited social interaction; 3) Suffering sorrow as a 'disqualified
being'; 4) Shuttling back and forth across the boundary between healthy and
epileptic; 5) Desperate struggle to meet the expectation of given role; 6) Self
empowering through self-restriction and realization. CONCLUSION: The findings
from this study show that both the enacted and felt stigma of epilepsy impact on
the life of married Korean women with epilepsy. Although the participants face
social and interpersonal restriction and prejudices, they try their best to
fulfill their role rather than to be cared for as patients. As the stigma and
hardships of the participants are related to lack of knowledge, health
professionals should focus not just on clinical intervention but also on
providing targeted educational programs and counseling for these women to dispel
the stigma of the disease and to increase their quality of life.
PMID- 28706166
TI - [Development and Effects of an Instructional Coaching Program Regarding Children
with Attention Deficit Hyperactivity Disorder for Elementary School Teachers].
AB - PURPOSE: The aim of this study was to identify the effects of a newly developed
instructional coaching program regarding Attention Deficit Hyperactivity Disorder
(ADHD) for teachers. METHODS: Seventy teachers participated in this study
involving a nonequivalent control group and a pretest-posttest design. The
instructional coaching program consisted of eight 60-minute sessions. The program
was developed through a theoretical development program involving six steps. To
evaluate the effects of the program, data were collected through self-report
questionnaires including the Knowledge Scale of Attention Deficit Disorder,
Attitude Scale of Primary School Teachers Experiencing Students with ADHD,
Practice Scale of Educational Intervention Activity, and the Korean ADHD Rating
Scale. Data were analyzed with an independent t test, a chi-square test, and an
ANCOVA using SPSS WIN version 20. RESULTS: The intervention program consisted of
3 sectors, 8 subjects, and 24 content items. The experimental group showed a
significant improvement in attitudes toward ADHD (F=22.83, p<.001). In addition,
teacher's knowledge regarding ADHD (F=7.16, p=.010) and the implementation of
instructional interventions (F=4.29, p=.043) improved. Further, teachers reported
a reduction in children's ADHD-related behavior (F=4.34, p=.041). Results showed
that the coaching program made a positive contribution to teaching skills and
understanding of school-age children with ADHD. CONCLUSION: The instructional
coaching program was well structured and significantly improved not only
teachers'attitudes, knowledge, and teaching skills but also the behavior of
children with ADHD in class. Therefore, the program is recommended as a means of
facilitating teaching and managing children with ADHD in class.
PMID- 28706167
TI - [Development and Validation of the Cancer-Specific Posttraumatic Growth
Inventory].
AB - PURPOSE: The purpose of this study was to develop a scale to evaluate
posttraumatic growth in patients with cancer and to examine the validity and
reliability of the scale. METHODS: A literature review, semi-structured patient
interviews and an expert panel consultation produced a 27 preliminary item
questionnaire. Participants were 150 cancer patients recruited to test the
reliability and validity of the preliminary scale. Data were analyzed using item
analysis, exploratory factor analysis, convergent validity and internal
consistency. RESULTS: Item reduction and exploratory factor analysis led to 23
items, grouped into five subscales which were labelled new possibilities (6
items), coping skills (5 items), preciousness of life (5 items), relating to
others (4 items), and personal strength (3 items). Convergent validity was
evaluated by total correlation with the Functional Assessment of Cancer Therapy
General (r=.45, p<.001). The final scale demonstrated satisfactory internal
consistency (Cronbach's alpha =.94). CONCLUSION: Findings from this study
indicate that the Cancer-Specific Posttraumatic Growth Inventory has validity and
reliability and is considered to be appropriate for assessing posttraumatic
growth in patients with cancer.
PMID- 28706168
TI - [The Effects of Violence Coping Program Based on Middle-Range Theory of
Resilience on Emergency Room Nurses' Resilience, Violence Coping, Nursing
Competency and Burnout].
AB - PURPOSE: The purpose of this study was to examine the effects of a violence
coping program (VCP) based on Polk's middle-range theory of resilience on nursing
competency, resilience, burnout, and the ability to cope with violence in nurses
working in emergency rooms. METHODS: A quasi-experimental study, with a
nonequivalent control group and a pretest-posttest design, was conducted.
Participants were 36 nurses who worked in emergency rooms and had experienced
violence; 18 nurses from D hospital and 18 nurses from C hospital were assigned
to the experimental and control groups, respectively. The experimental group
received the VCP twice per week for 8 weeks. RESULTS: Levels of resilience,
F=59.41, p<.001, active coping behavior, chi2=33.09, p<.001, and nursing
competency, F=59.41 p<.001, increased significantly and levels of passive coping
behavior, chi2=22.92, p<.001, and burnout, F=52.74, p<.001, decreased
significantly in the experimental group. CONCLUSION: The results suggest that the
VCP could be an effective strategy for reducing burnout and improving resilience,
active coping behavior, and nursing competency. Therefore, it would be a useful
intervention for improving the quality of nursing care provided in emergency
rooms.
PMID- 28706169
TI - [The Effect of a Movie-Based Nursing Intervention Program on Rehabilitation
Motivation and Depression in Stroke Patients].
AB - PURPOSE: The aim of this study was to develop and measure the effect of a movie
based-nursing intervention program designed to enhance motivation for
rehabilitation and reduce depression levels in stroke patients. METHODS: The
study used a quasi-experimental, nonequivalent control group and a pretest
posttest design. The 60 research subjects were assigned to the experimental
(n=30) or control group (n=30). The moviebased nursing intervention program was
provided for the experimental group during 60-minute sessions held once per week
for 10 weeks. The program consisted of patient education to strengthen motivation
for rehabilitation and reduce depression, watching movies to identify role
models, and group discussion to facilitate therapeutic interaction. RESULTS:
After 10 weeks of participation in the movie-based nursing intervention program,
the experimental group's rehabilitation motivation score was significantly
higher, F=1161.54 (within groups df=49, between groups df=1), p<.001, relative to
that observed in the control group. In addition, the experimental group's
depression score was significantly lower relative to that observed in the control
group, F=258.97 (within groups df=49, between groups df=1), p<.001. CONCLUSION:
The movie-based nursing intervention program could be used for stroke patients
experiencing psychological difficulties including reduced motivation for
rehabilitation and increased depression during the rehabilitation process.
PMID- 28706170
TI - [Multiple Factors in the Second Trimester of Pregnancy on Preterm Labor Symptoms
and Preterm Birth].
AB - PURPOSE: The aim of this study was to determine the influence of various factors
on preterm labor symptoms (PLS) and preterm birth (PB). METHODS: This prospective
cohort study included 193 women in the second stage of pregnancy. Multiple
characteristics including body mass index (BMI), smoking, and pregnancy
complications were collected through a self-report questionnaire. Pregnancy
stress and PLS were each measured with a related scale. Cervical length and birth
outcome were evaluated from medical charts. Multiple regression was used to
predict PLS and logistic regression was used to predict PB. RESULTS: Multiple
regression showed smoking experience, pregnancy complications and pregnancy
specific stress were predictors of PLS and accounted for 19.2% of the total
variation. Logistic regression showed predictors of PB to be twins (OR=13.68,
CI=3.72~50.33, p<.001), shorter cervix (<25mm) (OR=5.63, CI=1.29~24.54, p<.05),
BMI >25 (kg/m2) (OR=3.50, CI=1.35~9.04, p<.01) and a previous PB (OR=4.15,
CI=1.07~16.03, p<.05). CONCLUSION: The results of this study show that the
multiple factors affect stage II pregnant women can result in PLS or PB. And
preterm labor may predict PB. These findings highlight differences in predicting
variables for pretrm labor and for PB. Future research is needed to develop a
screening tool to predict the risk of preterm birth in pregnant women.
PMID- 28706171
TI - [Hermeneutic Phenomenological Study on Caring Experience of Spouses of Elderly
People with Dementia at Home].
AB - PURPOSE: This study aimed to understand and describe the caring experiences of
spouses of elderly people with dementia. METHODS: The hermeneutic
phenomenological method was used and participants were 12 spouses aged 65 and
over who were taking care of their husbands or wives with dementia at home. Data
were collected from individual in-depth interviews on participants' actual caring
experiences. Additionally, novels, movies, and memoirs on elderly couples with
partner who had dementia were included as data for the analysis. The qualitative
data analysis software program was used to manage and process the collected
qualitative data. Data were analyzed using hermeneutic phenomenological analysis
based on four fundamental existentials including lived body, lived space, lived
time, and lived others. RESULTS: Five essential themes emerged from the analysis:
1) body moving like an old machine, 2) swamp of despair filling with hope, 3)
sweet time after bitterness, 4) disappointed elderly couple in the empty nest,
and 5) unappreciation vs. empathetic feelings. These essential themes were
comprehensively summarized as "the road leading to the maturation of life with
dedication and hope while bearing the weight of caring based on the couple's
relationship." CONCLUSION: The findings indicate that the nature of the caring
experience of spouses of elderly individuals with dementia is filled with many
dynamic and paradoxical dimensions. Thus, results of the study would help with
developing interventions tailored specifically for elderly spouse caregivers to
support their role adaptation and ultimately improving their quality of life.
PMID- 28706172
TI - [The Effect of Health Coaching Programs on Self-Efficacy, Health Behaviors, and
Quality of Life in Hypertensive People Living in Poverty].
AB - PURPOSE: This study was designed to determine the effects of health coaching and
mediating variables on quantitative aspect of health in low-income hypertensive
people. METHODS: The experimental group for the current study consisted of 21
clients who received health coaching services, and the control group consisted of
22 clients who received home-visiting nursing services. Two groups received
health coaching or homevisiting nursing services once a week for 8 weeks. The
evaluation variables were self-efficacy, nutrition management, health behaviors,
self-rated health, and quality of life. RESULTS: The results revealed that the
level of nutrition management was significantly higher in the experimental group
than the control group (F=10.33, p=.005). CONCLUSION: These results confirm that
health coaching is a useful strategy that encourages clients to continuously
maintain their own health behaviors. Thus, the findings of the current study
provide useful data for establishing measures for the health management of those
afflicted with chronic disease, such as hypertension. Furthermore, health
coaching may be developed into useful intervention strategies for dealing with
chronic diseases and improving home-visiting nursing.
PMID- 28706173
TI - [Development and Evaluation of a Self-Reflection Program for Intensive Care Unit
Nurses Who Have Experienced the Death of Pediatric Patients].
AB - PURPOSE: This study aims to develop a self-reflection program for nurses who have
experienced the death of pediatric patients in the intensive care unit and to
evaluate its effectiveness. METHODS: The self-reflection program was developed by
means of the following four steps: establishment of the goal through
investigation of an initial request, drawing up the program, preliminary
research, and implementation and improvement of the program. The study employed a
methodological triangulation to evaluate the effectiveness of the program.
Participants were 38 nurses who had experienced the death of pediatric patients
(experimental group=15, control group=23); they were recruited using convenience
sampling. The self-reflection program was provided over 6 weeks (6 sessions).
Data were collected from April to August, 2014 and analyzed using t-tests and
content analysis. RESULTS: The quantitative results showed that changes in
personal growth (t=-6.33, p<.001) and burnout scores (z=-2.76, p=.005) were
better in the experimental group compared to the control group. The qualitative
results exhibited two themes, namely "personal growth" and "professional growth",
and ten sub-themes. CONCLUSION: The self-reflection program developed by this
study was effective in helping nurses who had experienced the death of pediatric
patients to achieve personal growth through self-reflection, and it was confirmed
that the program can be applied in a realistic clinical nursing setting.
Furthermore, it can be recommended as an intervention program for clinical
nurses.
PMID- 28706174
TI - [Development and Evaluation of a Motivational Interviewing Program for Exercise
Improvement in Persons with Physical Disabilities].
AB - PURPOSE: The aims of this study were to develop a motivational interviewing
program for exercise improvement in persons with physical disabilities and to
examine the effect of this motivational interviewing intervention. METHODS: The
study employed a nonequivalent control group pretest and posttest design. A total
of 62 persons with physical disabilities (30 in the experimental group, 32 in the
control group) were recruited from 2 community rehabilitation centers. The
experimental group received 8 sessions of a group motivational interviewing
program, scheduled once a week, with each session lasting 60 minutes. Test
measures were completed before the intervention, immediately after the end of the
intervention, 2 weeks later, and 6 weeks after the end of the intervention.
Measures included self-efficacy for exercise, decisional balance for exercise,
stage of change for exercise, regularity of exercise, exercise maintenance, and
independent living ability. Data were analyzed using the chi2-test, Fisher's
exact test, Independent samples t-test, and repeated measures ANOVA, conducted
using IBM SPSS Statistics version 18. RESULTS: The experimental group showed a
significant increase in self-efficacy for exercise (F=50.98, p<.001), benefit
(pros) of exercise (F=24.16, p<.001), and independent living ability (F=50.94,
p<.001), and a significant decrease in loss (cons) of exercise (F=26.50, p<.001).
There were significant differences between the two groups in stages of change for
exercise (p<.001), regularity of exercise (p<.001), and exercise maintenance
(chi2=26.61, p<.001). CONCLUSION: The motivational interviewing program has the
potential to improve exercise levels in persons with physical disabilities.
PMID- 28706175
TI - [Characteristics and Risk Factors for Falls in Tertiary Hospital Inpatients].
AB - PURPOSE: The aim of this study was to explore characteristics of and risk factors
for accidental inpatient falls. METHODS: Participants were classified as fallers
or non-fallers based on the fall history of inpatients in a tertiary hospital in
Seoul between June 2014 and May 2015. Data on falls were obtained from the fall
report forms and data on risk factors were obtained from the electronic nursing
records. Characteristics of fallers and non-fallers were analyzed using
descriptive statistics. Risk factors for falls were identified using univariate
analyses and logistic regression analysis. RESULTS: Average length of stay prior
to the fall was 21.52 days and average age of fallers was 61.37 years. Most falls
occurred during the night shifts and in the bedroom and were due to sudden leg
weakness during ambulation. It was found that gender, BMI, physical problems such
elimination, gait, vision and hearing and medications such as sleeping pills,
antiarrhythmics, vasodilators, and muscle relaxant were statistically significant
factors affecting falls. CONCLUSION: The findings show that there are significant
risk factors such as BMI and history of surgery which are not part of fall
assessment tools. There are also items on fall assessment tools which are not
found to be significant such as mental status, emotional unstability, dizziness,
and impairment of urination. Therefore, these various risk factors should be
examined in the fall risk assessments and these risk factors should be considered
in the development of fall assessment tools.
PMID- 28706176
TI - Effects of a Memory and Visual-Motor Integration Program for Older Adults Based
on Self-Efficacy Theory.
AB - PURPOSE: This study was conducted to verify the effects of a memory and visual
motor integration program for older adults based on self-efficacy theory.
METHODS: A non-equivalent control group pretest-posttest design was implemented
in this quasi-experimental study. The participants were 62 older adults from
senior centers and older adult welfare facilities in D and G city (Experimental
group=30, Control group=32). The experimental group took part in a 12-session
memory and visual-motor integration program over 6 weeks. Data regarding memory
self-efficacy, memory, visual-motor integration, and depression were collected
from July to October of 2014 and analyzed with independent t-test and Mann
Whitney U test using PASW Statistics (SPSS) 18.0 to determine the effects of the
interventions. RESULTS: Memory self-efficacy (t=2.20, p=.031), memory (Z=-2.92,
p=.004), and visual-motor integration (Z=-2.49, p=.013) increased significantly
in the experimental group as compared to the control group. However, depression
(Z=-0.90, p=.367) did not decrease significantly. CONCLUSION: This program is
effective for increasing memory, visual-motor integration, and memory self
efficacy in older adults. Therefore, it can be used to improve cognition and
prevent dementia in older adults.
PMID- 28706177
TI - Pitfalls in surveillance for hepatocellular carcinoma: How successful is it in
the real world?
AB - BACKGROUND/AIMS: Surveillance for hepatocellular carcinoma (HCC) with ultrasound
in high-risk populations is generally believed to improve opportunities for
treatment. However, tumors are still missed due to various factors. This study
explores success versus failure of HCC surveillance. METHODS: This is a
retrospective study of 1,125 HCC cases. Categories considered for successful
detection were largest tumor <=3.0 cm, single tumors <=3.0 cm and <=2.0 cm, and
adherence to Milan criteria. Examined factors were age <60 years, gender, rural
residence, body-mass index (BMI), hepatitis infection, smoking, diabetes,
hyperlipidemia, cirrhosis, ascites, and Model for End-Stage Liver Disease <10.
RESULTS: HCC was found on surveillance in 257 patients with a mean tumor size of
3.17 cm; multiple tumors were seen in 28% of cases, bilateral tumors in 7.4%, and
vascular invasion in 3.7%. Surveillance was successful in 61.5% of cases
involving a largest tumor <=3.0 cm, with BMI >=35 negatively affecting detection
(odds ratio [OR] 0.28, P=0.014) and cirrhosis positively affecting detection (OR
2.31, P=0.036). Ultrasound detected 19.1% of single tumors <=2.0 cm with ascites
improving the detection rate (OR 3.89, P=0.001). Finally, adherence to Milan
criteria occurred in 75.1% of cases, revealing negative associations with
diabetes (OR 0.48, P=0.044 and male gender (OR 0.49, P=0.08). CONCLUSIONS:
Although surveillance is recommended for HCC, not all surveillance ultrasound are
ideal. Tumor detection can depend on gender, BMI, diabetes, cirrhosis, and
ascites and is achieved in 19.1-75% of cases depending on the definition of
success. Closer follow-up or additional imaging might be necessary for some
patient subgroups.
PMID- 28706178
TI - Surgery for Cardiac Papillary Fibroelastoma: A 12-Year Single Institution
Experience.
AB - BACKGROUND We reviewed our clinical experience with cardiac papillary
fibroelastoma from 2005 to 2017. The objective of this study was to investigate
the clinical and operative data, as well as the early survival rate and immediate
postoperative complications. MATERIAL AND METHODS We performed a retrospective
analysis of 11 patients (eight males and three females) who underwent resection
of cardiac papillary fibroelastoma in our institution. RESULTS Mean age at tumor
diagnosis was 60+/-14 years. The mean dimension of the tumor was 14+/-11 mm. The
most common symptoms were dyspnea, palpitation, and angina pectoris, while one
patient had recurrent fever attacks and another patient had a transient ischemic
attack. Two patients had concomitant malignant tumors (cervical and colon
carcinoma) and another two had concomitant benign neoplasms (liver cyst and
thyroid adenoma). Bypass and cross clamp times were 77+/-32 minutes and 54+/-18
minutes, respectively. The tumors were found predominantly on cardiac valves
(n=7). In eight cases, only tumor extirpation was performed, whereas in the other
three cases, the valves had to be replaced. The mean intensive care unit length
of stay was 1.1+/-0.3 days and there was no in-hospital mortality. All patients
were alive at one-year follow-up and the survival rate was 91% in the mean follow
up period of 4.15 years. CONCLUSIONS The surgical treatment of cardiac papillary
fibroelastoma was curative and safe. Thus, potential complications such as
embolization or mechanical irritation of the valves can be avoided without high
surgical risk.
PMID- 28706179
TI - Nilotinib Induced Recurrent Gastric Polyps: Case Report and Review of Literature.
AB - BACKGROUND Tyrosine kinase inhibitors (TKIs) are currently an important targeted
drug class in the treatment of chronic myeloid leukemia (CML). Imatinib was the
first approved TKI for CML in 2001. Nilotinib is a second-generation TKI,
approved in 2007; it inhibits BCR-ABL, PDGFR, and c-KIT, and is 30 times more
potent than imatinib. Tyrosine kinase enzymes are expressed in multiple tissues
and are involved in several signaling pathways; they have been shown to have
several off-target side effects. CASE REPORT We report a case of an elderly male
with CML and no history of gastrointestinal diseases, treated with nilotinib, and
developed recurrent gastric polyps after three years of treatment. We excluded
common causes of gastric polyps and therefore considered nilotinib as a probable
cause of recurrent gastric polyps. CONCLUSIONS Recurrent gastric polyps could be
a potential side effect of nilotinib treatment. Careful long-term monitoring of
patients on TKI therapy is necessary and further long-term studies of TKI side
effects are needed.
PMID- 28706180
TI - Serum Uric Acid and Arterial Function After Renal Transplantation.
AB - BACKGROUND Hyperuricemia is associated with an increased risk of cardiovascular
disease and chronic allograft nephropathy after renal transplantation. It has
recently been demonstrated that treatment of asymptomatic hyperuricemia is
associated with improved patient and graft survival; although, the underlying
mechanisms remain elusive. The present study investigated the association of
serum uric acid (SUA) and systemic arterial function after renal transplantation.
MATERIAL AND METHODS In a cross-sectional study, arterial function was analyzed
in 54 renal transplant recipients by means of pulse wave analysis. Different
measurement techniques were combined providing data on pulse wave velocity,
augmentation index, small and large artery elasticity, and total peripheral
vascular resistance. RESULTS The prevalence of hyperuricemia was 87.0%, and 33.3%
of renal transplant recipients received SUA lowering medication. The median SUA
concentration was 7.4 mg/dL. There was no significant difference in all the
aforementioned parameters in patients with a SUA <7.4 versus >7.4 mg/dL (p>0.05
each) and no significant differences between hyperuricemic patients with versus
without SUA lowering medication. Linear regression analysis between SUA and both
pulse wave velocity and augmentation index showed no significant association
(p>0.05 each). This finding remained consistent after adjustment of data for age,
time on dialysis, time since transplantation, and systolic blood (partial
correlation analysis, p>0.05). CONCLUSIONS Neither the concentration of SUA nor
the pharmacological treatment of hyperuricemia had measurable effects on arterial
stiffness. Thus, the beneficial effects of SUA lowering treatment on patient and
graft survival cannot be explained by direct effects on arterial function in the
study population.
PMID- 28706181
TI - Effects of an Enriched Extract of Paeoniflorin, a Monoterpene Glycoside used in
Chinese Herbal Medicine, on Cholesterol Metabolism in a Hyperlipidemic Rat Model.
AB - BACKGROUND Paeoniflorin is a monoterpene glycoside extracted from the roots of
Paeonia lactiflora and is used in Chinese herbal medicine to treat
hyperlipidemia. The aim of this study was to evaluate the effects of an enriched
extract of paeoniflorin on cholesterol levels, hemodynamics, and oxidative stress
in a hyperlipidemic rat model. MATERIAL AND METHODS Male Sprague-Dawley rats were
fed high-cholesterol diets and treated with three different doses of paeoniflorin
for 12 weeks. The effects of paeoniflorin treatment were assessed on cholesterol
levels, cholesterol metabolism, red blood cell vascular flow using hemorheology,
antioxidant enzymes, and expression of the rate-limiting enzyme in the mevalonate
pathway, 3-hydroxy-3-methylglutharyl-coenzyme A reductase (HMG-CoAR). Rat liver
histology and immunohistochemical analysis were performed to evaluate the
expression of nuclear factor erythroid 2-related factor 2 (Nrf2), cytochrome P450
7A1 (CYP7A1), and peroxisome proliferator-activated receptors (PPAR)-alpha.
Protein expression HMG-CoAR, low-density lipoprotein receptor (LDLR), PPAR-alpha
and CYP7A1 was measured by Western blotting. Antioxidant activity in rat liver
was determined by measuring superoxide dismutase (SOD) and malondialdehyde (MDA).
RESULTS Serum and hepatic cholesterol, hepatic steatosis and the products of
cholesterol metabolism were reduced by paeoniflorin treatment, which also reduced
the activity of HMG-CoAR and upregulated the expression of LDLR, PPAR-alpha, and
CYP7A1 expression, increased SOD, decreased MDA, and upregulated Nrf2 expression.
CONCLUSIONS The findings of this study in a rat model of hyperlipidemia have
shown that paeoniflorin regulates hepatic cholesterol synthesis and metabolism
and may also protect the liver from oxidative stress.
PMID- 28706182
TI - Ultra strong pyroprotein fibres with long-range ordering.
AB - Silks are protein-based natural structured materials with an unusual combination
of high strength and elongation. Their unique microstructural features composed
of hard beta-sheet crystals aligned within a soft amorphous region lead to the
robust properties of silks. Herein we report a large enhancement in the intrinsic
properties of silk through the transformation of the basic building blocks into a
poly-hexagonal carbon structure by a simple heat treatment with axial stretching.
The carbon clusters originating from the beta-sheet retain the preferred
orientation along the fibre axis, resulting in a long-range-ordered graphitic
structure by increasing heat-treatment temperatures and leading improvements in
mechanical properties with a maximum strength and modulus up to ~2.6 and ~470
GPa, respectively, almost four and thirty times surpassing those of raw silk.
Moreover, the formation of sp 2 carbon configurations induce a significant change
in the electrical properties (e.g. an electrical conductivity up to 4.37 * 103 S
cm-1).The mechanical properties of silk are determined by tight stacks of sheet
like peptide crystals distributed in amorphous regions. Here, the authors heat
and stretch silk fibres to align these crystal into a long range ordered carbon
structure and dramatically enhance the silk strength.
PMID- 28706183
TI - Modulation of Interleukin-12 activity in the presence of heparin.
AB - Glycosaminoglycans (GAGs), especially heparin and heparan sulfate (HS), modulate
the functions of numerous cytokines. The aims of this multidisciplinary research
were to characterize heparin binding to interleukin-12 (IL-12) and determine the
mechanism(s) by which heparin influences IL-12 bioactivity. Heparin and HS were
found to bind human IL-12 (hIL-12) with low micromolar affinity and increase hIL
12 bioactivity by more than 6-fold. Conversely, other GAGs did not demonstrate
significant binding, nor did their addition affect hIL-12 bioactivity.
Biophysical studies demonstrated that heparin induced only minor conformational
changes while size-exclusion chromatography and small angle X-ray scattering
studies indicated that heparin induced dimerization of hIL-12. Heparin modestly
protected hIL-12 from proteolytic degradation, however, this was not a likely
mechanism for increased cytokine activity in vitro. Flow cytometry studies
revealed that heparin increased the amount of hIL-12 bound to cell surfaces.
Heparin also facilitated hIL-12 binding and signaling in cells in which both hIL
12 receptor subunits were functionally deleted. Results of this study demonstrate
a new role for heparin in modulating the biological activity of IL-12.
PMID- 28706184
TI - Testosterone promotes either dominance or submissiveness in the Ultimatum Game
depending on players' social rank.
AB - Endogenous testosterone promotes behaviours intended to enhance social dominance.
However, recent research suggests that testosterone enhances strategic social
behaviour rather than dominance seeking behaviour. This possibility has not been
tested in a population whose members are known to vary in social status. Here, we
explored the relationship between pre-existing social status and salivary
testosterone level among members of a rugby team at a Japanese university, where
a strong seniority norm maintains hierarchical relationships. Participants played
a series of one-shot Ultimatum Games (UG) both as proposer and responder.
Opponents were anonymised but of known seniority. We analysed participants'
acquiescence (how much more they offered beyond the lowest offer they would
accept). The results showed that, among the most senior participants, higher
testosterone was associated with lower acquiescence. Conversely, higher
testosterone among the lower-status participants was associated with higher
acquiescence. Our results suggest that testosterone may enhance socially dominant
behaviour among high-status persons, but strategic submission to seniority among
lower-status persons.
PMID- 28706185
TI - Deep Learning for Fully-Automated Localization and Segmentation of Rectal Cancer
on Multiparametric MR.
AB - Multiparametric Magnetic Resonance Imaging (MRI) can provide detailed information
of the physical characteristics of rectum tumours. Several investigations suggest
that volumetric analyses on anatomical and functional MRI contain clinically
valuable information. However, manual delineation of tumours is a time consuming
procedure, as it requires a high level of expertise. Here, we evaluate deep
learning methods for automatic localization and segmentation of rectal cancers on
multiparametric MR imaging. MRI scans (1.5T, T2-weighted, and DWI) of 140
patients with locally advanced rectal cancer were included in our analysis,
equally divided between discovery and validation datasets. Two expert
radiologists segmented each tumor. A convolutional neural network (CNN) was
trained on the multiparametric MRIs of the discovery set to classify each voxel
into tumour or non-tumour. On the independent validation dataset, the CNN showed
high segmentation accuracy for reader1 (Dice Similarity Coefficient (DSC = 0.68)
and reader2 (DSC = 0.70). The area under the curve (AUC) of the resulting
probability maps was very high for both readers, AUC = 0.99 (SD = 0.05). Our
results demonstrate that deep learning can perform accurate localization and
segmentation of rectal cancer in MR imaging in the majority of patients. Deep
learning technologies have the potential to improve the speed and accuracy of MRI
based rectum segmentations.
PMID- 28706186
TI - Twins methods quantitatively explore the genetic impact on children and
adolescents brain gray matter volume.
AB - The gray matter volumes of 58 pairs of twins ranging in age from 12 to 18 were
measured by MRI to explore the genetic and environmental impacts on gray matter
volume in twin children and adolescents. By means of A/C/E structural equation
modeling, it was found that the gray matter volume in children and adolescents
was jointly affected by genetic (A: 0.89) and environmental factors while genetic
factors play a greater role. The gray matter volume in frontal lobe, parietal
lobe, occipital lobe and lateral temporal lobe was mainly affected by genetics
(A: 0.7-0.89), where as the gray matter volume in medial temporal lobe and
cingulate cortex was affected by both genetics and environment.
PMID- 28706187
TI - DELAY OF GERMINATION1 requires PP2C phosphatases of the ABA signalling pathway to
control seed dormancy.
AB - The time of seed germination is a major decision point in the life of plants
determining future growth and development. This timing is controlled by seed
dormancy, which prevents germination under favourable conditions. The plant
hormone abscisic acid (ABA) and the protein DELAY OF GERMINATION 1 (DOG1) are
essential regulators of dormancy. The function of ABA in dormancy is rather well
understood, but the role of DOG1 is still unknown. Here, we describe four
phosphatases that interact with DOG1 in seeds. Two of them belong to clade A of
type 2C protein phosphatases: ABA-HYPERSENSITIVE GERMINATION 1 (AHG1) and AHG3.
These phosphatases have redundant but essential roles in the release of seed
dormancy epistatic to DOG1. We propose that the ABA and DOG1 dormancy pathways
converge at clade A of type 2C protein phosphatases.The DOG1 protein is a major
regulator of seed dormancy in Arabidopsis. Here, Nee et al. provide evidence that
DOG1 can interact with the type 2C protein phosphatases AHG1 and AHG3 and that
this represents the convergence point of the DOG1-regulated dormancy pathway and
signalling by the plant hormone abscisic acid.
PMID- 28706188
TI - Lack of Social Support Raises Stress Vulnerability in Rats with a History of
Ancestral Stress.
AB - Stress is a primary risk factor for psychiatric disorders. However, it is not
fully understood why some stressed individuals are more vulnerable to psychiatric
disorders than others. Here, we investigated whether multigenerational ancestral
stress produces phenotypes that are sensitive to depression-like symptoms in
rats. We also examined whether social isolation reveals potentially latent
sensitivity to depression-like behaviours. F4 female rats born to a lineage of
stressed mothers (F0-F3) received stress in adulthood while housed in pairs or
alone. Social isolation during stress induced cognitive and psychomotor
retardation only in rats exposed to ancestral stress. Social isolation also
hampered the resilience of the hypothalamic-pituitary-adrenal axis to chronic
stress and reduced hippocampal volume and brain-derived neurotrophic factor
(BDNF) expression. Thus, synergy between social isolation and stress may unmask a
latent history of ancestral stress, and raises vulnerability to mental health
conditions. The findings support the notion that social support critically
promotes stress coping and resilience.
PMID- 28706189
TI - Vertical sleeve gastrectomy reverses diet-induced gene-regulatory changes
impacting lipid metabolism.
AB - Vertical sleeve gastrectomy (VSG) produces sustainable weight loss, remission of
type 2 diabetes (T2D), and improvement of nonalcoholic fatty liver disease
(NAFLD). However, the molecular mechanisms underlying the metabolic benefits of
VSG have remained elusive. According to our previous results, diet-induced
obesity induces epigenetic modifications to chromatin in mouse liver. We
demonstrate here that VSG in C57BL/6J wild-type male mice can reverse these
chromatin modifications and thereby impact the expression of key metabolic genes.
Genes involved in lipid metabolism, especially omega-6 fatty acid metabolism, are
up-regulated in livers of mice after VSG while genes in inflammatory pathways are
down-regulated after VSG. Consistent with gene expression changes, regulatory
regions near genes involved in inflammatory response displayed decreased
chromatin accessibility after VSG. Our results indicate that VSG induces global
regulatory changes that impact hepatic inflammatory and lipid metabolic pathways,
providing new insight into the mechanisms underlying the beneficial metabolic
effects induced by VSG.
PMID- 28706190
TI - Clean Power Generation from the Intractable Natural Coalfield Fires: Turn Harm
into Benefit.
AB - The coal fires, a global catastrophe for hundreds of years, have been proved
extremely difficult to control, and hit almost every coal-bearing area globally.
Meanwhile, underground coal fires contain tremendous reservoir of geothermal
energy. Approximately one billion tons of coal burns underground annually in the
world, which could generate ~1000 GW per annum. A game-changing approach,
environmentally sound thermal energy extraction from the intractable natural
coalfield fires, is being developed by utilizing the waste energy and reducing
the temperature of coalfield fires at the same time. Based on the Seebeck effect
of thermoelectric materials, the temperature difference between the heat medium
and cooling medium was employed to directly convert thermal energy into clean
electrical energy. By the time of December 2016, the power generation from a
single borehole at Daquan Lake fire district in Xinjiang has been exceeded 174.6
W. The field trial demonstrates that it is possible to exploit and utilize the
waste heat resources in the treated coal fire areas. It promises a significant
impact on the structure of global energy generation and can also promote progress
in thermoelectric conversion materials, geothermal exploration, underground coal
fires control and other energy related areas.
PMID- 28706191
TI - Aldehyde dehydrogenase 1-positive nigrostriatal dopaminergic fibers exhibit
distinct projection pattern and dopamine release dynamics at mouse dorsal
striatum.
AB - Aldehyde dehydrogenase 1 (ALDH1A1)-positive dopaminergic (DA) neurons at the
ventral substantia nigra pars compacta (SNpc) preferentially degenerate in
Parkinson's disease (PD). Their projection pattern and dopamine release
properties, however, remains uncharacterized. Here we show that ALDH1A1-positive
axons project predominantly to the rostral two-thirds of dorsal striatum. A
portion of these axons converge on a small fraction of striosome compartments
restricted to the dorsolateral striatum (DLS), where less dopamine release was
measured compared to the adjacent matrix enriched with the ALDH1A1-negative
axons. Genetic ablation of Aldh1a1 substantially increases the dopamine release
in striosomes, but not in matrix. Additionally, the presence of PD-related human
alpha-synuclein A53T mutant or dopamine transporter (DAT) blockers also
differentially affects the dopamine output in striosomes and matrix. Together,
these results demonstrate distinct dopamine release characteristics of ALDH1A1
positive DA fibers, supporting a regional specific function of ALDH1A1 in
regulating dopamine availability/release in striatum.
PMID- 28706192
TI - Integrative Profiling of Bee Communities from Habitats of Tropical Southern
Yunnan (China).
AB - Understanding and managing pollination service is hindered by taxonomic
impediments and paucity of data, particularly in the tropics. Herein we apply
integrative species delineation and taxonomy to test impacts of land use on the
diversity of bee communities within Xishuangbanna (Yunnan, south China), a highly
biodiverse tropical region which has undergone extensive land conversion to
rubber plantation. 128 Operational Taxonomic Units (OTU) were inferred by an
iterative and integrative approach. Bee activity differed significantly across
land use samples, although community composition corresponded more to level of
vegetation density, when accounting for spatial structure. Species diversity was
high in young rubber plantations, although composition overlapped with other
species-rich habitats (natural forest edge and river banks), and older
plantations (>8 years) showed very low diversity under all measures. Community
structures were similar between the natural forest interior and edge, although
analysis indicated contrasting drivers of diversity, with clustering in the
interior and overdispersion in the forest edge. Further, phylogenetic diversity
and derived indices were underestimated when reference data were omitted from
analysis. The description of bee communities herein permits more informed choices
in land management with respect to ensuring continuation of essential services by
bees.
PMID- 28706193
TI - Polydextrose changes the gut microbiome and attenuates fasting triglyceride and
cholesterol levels in Western diet fed mice.
AB - Obesity and dyslipidemia are hallmarks of metabolic and cardiovascular diseases.
Polydextrose (PDX), a soluble fiber has lipid lowering effects. We hypothesize
that PDX reduces triglycerides and cholesterol by influencing gut microbiota,
which in turn modulate intestinal gene expression. C57BL/6 male mice were fed a
Western diet (WD) +/-75 mg PDX twice daily by oral gavage for 14 days. Body
weight and food intake were monitored daily. Fasting plasma lipids, caecal
microbiota and gene expression in intestine and liver were measured after 14 days
of feeding. PDX supplementation to WD significantly reduced food intake (p <
0.001), fasting plasma triglyceride (p < 0.001) and total cholesterol (p < 0.05).
Microbiome analysis revealed that the relative abundance of Allobaculum,
Bifidobacterium and Coriobacteriaceae taxa associated with lean phenotype,
increased in WD + PDX mice. Gene expression analysis with linear mixed-effects
model showed consistent downregulation of Dgat1, Cd36, Fiaf and upregulation of
Fxr in duodenum, jejunum, ileum and colon in WD + PDX mice. Spearman correlations
indicated that genera enriched in WD + PDX mice inversely correlated with fasting
lipids and downregulated genes Dgat1, Cd36 and Fiaf while positively with
upregulated gene Fxr. These results suggest that PDX in mice fed WD promoted
systemic changes via regulation of the gut microbiota and gene expression in
intestinal tract.
PMID- 28706194
TI - Anti-TNF-alpha agents and endothelial function in rheumatoid arthritis: a
systematic review and meta-analysis.
AB - Rheumatoid arthritis (RA) has been associated with endothelial dysfunction, a
pathophysiological feature of atherosclerosis. Our aim was to determine whether
TNF-alpha blockade has a beneficial effect on endothelial function in RA. We
performed a systematic review with meta-analysis to evaluate the effect of anti
TNF-alpha agents on endothelial function in RA patients. MedLine, Cochrane
CENTRAL and SCOPUS were searched up to March 2016. Inclusion criteria were: 1)
randomised controlled trial (RCT), quasi-RCT, before-after cohort study; 2)
including RA patients; 3) treatment with anti-TNF-alpha medications; 4)
evaluating the change from baseline in endothelial function. The search strategy
retrieved 180 records, of which 20 studies were included in the systematic
review. Pooled analysis using a random-effects model demonstrated a significant
improvement in endothelial function following anti-TNF-alpha treatment (SDM
0.987, 95%CI [0.64-1.33], p < 0.0001). Generalisation of the results of the meta
analysis may be limited due to the presence of heterogeneity (I2 = 82.65%, p <
0.001) and evidence of possible publication bias. Meta-regression showed that
endothelial function measurement technique was a significant contributor to
heterogeneity. In conclusion, although limited by the methodological quality of
the included studies, our meta-analysis suggests that anti-TNF-alpha treatment
may improve endothelial function in RA patients.
PMID- 28706195
TI - Effect of Nb2O5 doping on improving the thermo-mechanical stability of sealing
interfaces for solid oxide fuel cells.
AB - Nb2O5 is added to a borosilicate sealing system to improve the thermo-mechanical
stability of the sealing interface between the glass and Fe-Cr metallic
interconnect (Crofer 22APU) in solid oxide fuel cells (SOFCs). The thermo
mechanical stability of the glass/metal interface is evaluated experimentally as
well as by using a finite element analysis (FEA) method. The sealing glass doped
with 4 mol.% Nb2O5 shows the best thermo-mechanical stability, and the sealing
couple of Crofer 22APU/glass/GDC (Gd0.2Ce0.8O1.9) remains intact after 50 thermal
cycles. In addition, all sealing couples show good joining after being held at
750 degrees C for 1000 h. Moreover, the possible mechanism on the thermo
mechanical stability of sealing interface is investigated in terms of stress
based and energy-based perspectives.
PMID- 28706196
TI - Synaptic GAP and GEF Complexes Cluster Proteins Essential for GTP Signaling.
AB - GTPase-activating proteins (GAPs) and guanine exchange factors (GEFs) play
essential roles in regulating the activity of small GTPases. Several GAPs and
GEFs have been shown to be present at the postsynaptic density (PSD) within
excitatory glutamatergic neurons and regulate the activity of glutamate
receptors. However, it is not known how synaptic GAP and GEF proteins are
organized within the PSD signaling machinery, if they have overlapping
interaction networks, or if they associate with proteins implicated in
contributing to psychiatric disease. Here, we determine the interactomes of three
interacting GAP/GEF proteins at the PSD, including the RasGAP Syngap1, the ArfGAP
Agap2, and the RhoGEF Kalirin, which includes a total of 280 interactions. We
describe the functional properties of each interactome and show that these
GAP/GEF proteins are highly associated with and cluster other proteins directly
involved in GTPase signaling mechanisms. We also utilize Agap2 as an example of
GAP/GEFs localized within multiple neuronal compartments and determine an
additional 110 interactions involving Agap2 outside of the PSD. Functional
analysis of PSD and non-PSD interactomes illustrates both common and unique
functions of Agap2 determined by its subcellular location. Furthermore, we also
show that these GAPs/GEFs associate with several proteins involved in psychiatric
disease.
PMID- 28706197
TI - Completeness of Community Structure in Networks.
AB - By defining a new measure to community structure, exclusive modularity, and based
on cavity method of statistical physics, we develop a mathematically principled
method to determine the completeness of community structure, which represents
whether a partition that is either annotated by experts or given by a community
detection algorithm, carries complete information about community structure in
the network. Our results demonstrate that the expert partition is surprisingly
incomplete in some networks such as the famous political blogs network,
indicating that the relation between meta-data and community structure in real
world networks needs to be re-examined. As a byproduct we find that the exclusive
modularity, which introduces a null model based on the degree-corrected
stochastic block model, is of independent interest. We discuss its applications
as principled ways of detecting hidden structures, finding hierarchical
structures without removing edges, and obtaining low-dimensional embedding of
networks.
PMID- 28706198
TI - Inhibitory effect of eugenol on seed germination and pre-harvest sprouting of
hybrid rice (Oryza sativa L.).
AB - Pre-harvest sprouting (PHS) is a constrain problem in hybrid rice production. The
present study was conducted to investigate the inhibitory effect of eugenol on
seed germination and PHS of hybrid rice variety (Qian You 1). The results showed
that seed germination speed and the activities of alpha-amylase were inhibited by
eugenol pre-soaking and these effects enhanced with the increasing of eugenol
concentrations; while seedling growth was not negatively affected. In field
trials, eugenol application caused a significant decline in PHS as compared with
control, whereas no sustained inhibition in post-harvested seed germination was
observed. The HPLC analysis indicated that eugenol raised the internal ABA
content by 1-4 times more than control, and seeds treated with eugenol had
relatively lower OsABA8OH2 and higher transcript levels of OsNCED2 expression
during early stages of seed imbibitions. In addition, seed germinated faster
after GA3 application than eugenol alone, and seed endogenous ABA content
decreased obviously. It suggested that eugenol strongly delayed seed germination
and the PHS in the field, which might be mainly due to the increased ABA contents
caused by eugenol. However, the phenomenon of delayed germination and high ABA
content caused by eugenol could be effectively recovered by exogenous GA3.
PMID- 28706199
TI - Defective Sphingosine-1-phosphate metabolism is a druggable target in
Huntington's disease.
AB - Huntington's disease is characterized by a complex and heterogeneous pathogenic
profile. Studies have shown that disturbance in lipid homeostasis may represent a
critical determinant in the progression of several neurodegenerative disorders.
The recognition of perturbed lipid metabolism is only recently becoming evident
in HD. In order to provide more insight into the nature of such a perturbation
and into the effect its modulation may have in HD pathology, we investigated the
metabolism of Sphingosine-1-phosphate (S1P), one of the most important bioactive
lipids, in both animal models and patient samples. Here, we demonstrated that S1P
metabolism is significantly disrupted in HD even at early stage of the disease
and importantly, we revealed that such a dysfunction represents a common
denominator among multiple disease models ranging from cells to humans through
mouse models. Interestingly, the in vitro anti-apoptotic and the pro-survival
actions seen after modulation of S1P-metabolizing enzymes allows this axis to
emerge as a new druggable target and unfolds its promising therapeutic potential
for the development of more effective and targeted interventions against this
incurable condition.
PMID- 28706200
TI - Global transcriptome analysis identifies differentially expressed genes related
to lipid metabolism in Wagyu and Holstein cattle.
AB - Fat deposition of beef cattle varies between breeds. However, the regulation
mechanism is still not elucidated completely at molecular level. In the present
study, we comparatively analyzed transcriptome of subcutaneous adipose tissue
between Wagyu and Holstein cattle with a significant difference in fat deposition
to identify key genes associated with fat metabolism and adipogenesis by high
throughput RNA-seq technology. A total of 59,149,852 and 69,947,982 high quality
reads were generated, respectively. With further analysis, 662 differentially
expressed genes were identified. Gene Ontology and KEGG pathway analysis revealed
that many differentially expressed genes were enriched in several biological
processes and pathways relevant to adipogenesis and lipid metabolism, in which
PPAR and fatty acid metabolism signaling pathways with related genes such as
PPARgamma, PLIN2 and ELOVL6 et al. play a critical role. Protein-protein
interaction network analysis showed EGR1, FOS, SERPINE1, AGT, MMP2 may have great
impact on adipocyte differentiation and adipogenesis. Moreover, potential
alternative splicing events and single nucleotide polymorphisms (SNPs) were also
identified. In summary, we comprehensively analyzed and discussed the
transcriptome of subcutaneous adipose tissue of Wagyu and Holstein cattle, which
might provide a theoretical basis for better understanding molecular mechanism of
fat metabolism and deposition in beef cattle.
PMID- 28706201
TI - Genotypic variability based association identifies novel non-additive loci DHCR7
and IRF4 in sero-negative rheumatoid arthritis.
AB - Sero-negative rheumatoid arthritis (RA) is a highly heterogeneous disorder with
only a few additive loci identified to date. We report a genotypic variability
based genome-wide association study (vGWAS) of six cohorts of sero-negative RA
recruited in Europe and the US that were genotyped with the Immunochip. A two
stage approach was used: (1) a mixed model to partition dichotomous phenotypes
into an additive component and non-additive residuals on the liability scale and
(2) the Levene's test to assess equality of the residual variances across
genotype groups. The vGWAS identified rs2852853 (P = 1.3e-08, DHCR7) and
rs62389423 (P = 1.8e-05, near IRF4) in addition to two previously identified loci
(HLA-DQB1 and ANKRD55), which were all statistically validated using cross
validation. DHCR7 encodes an enzyme important in cutaneous synthesis of vitamin D
and DHCR7 mutations are believed to be important for early humans to adapt to
Northern Europe where residents have reduced ultraviolet-B exposure and tend to
have light skin color. IRF4 is a key locus responsible for skin color, with a
vitamin D receptor-binding interval. These vGWAS results together suggest that
vitamin D deficiency is potentially causal of sero-negative RA and provide new
insights into the pathogenesis of the disorder.
PMID- 28706203
TI - Spectral dependence of nonlinear absorption in ordered silver metallic nanoprism
arrays.
AB - Ordered metallic nanoprism arrays have been proposed as novel and versatile
systems for the observation of nonlinear effects such as nonlinear absorption.
The study of the effect of the local field reinforcement on the fast optical
third order nonlinear response around the Surface Plasmon Resonance is of great
interest for many plasmonic applications. In this work, silver nanoprism arrays
have been synthesized by the nanosphere lithography method. A low repetition rate
tunable picosecond laser source was used to study the irradiance and wavelength
dependence of the nonlinear absorption properties around the dipolar and
quadrupolar resonances of the nanoarray with the use of the z-scan technique. The
irradiance dependence of the on-resonance nonlinearity was studied, and a
spectral region where nonlinear absorption is negligible was identified. This is
important for the possible application of these materials in optical information
processing devices.
PMID- 28706202
TI - Near-infrared autofluorescence induced by intraplaque hemorrhage and heme
degradation as marker for high-risk atherosclerotic plaques.
AB - Atherosclerosis is a major cause of mortality and morbidity, which is mainly
driven by complications such as myocardial infarction and stroke. These
complications are caused by thrombotic arterial occlusion localized at the site
of high-risk atherosclerotic plaques, of which early detection and therapeutic
stabilization are urgently needed. Here we show that near-infrared
autofluorescence is associated with the presence of intraplaque hemorrhage and
heme degradation products, particularly bilirubin by using our recently created
mouse model, which uniquely reflects plaque instability as seen in humans, and
human carotid endarterectomy samples. Fluorescence emission computed tomography
detecting near-infrared autofluorescence allows in vivo monitoring of intraplaque
hemorrhage, establishing a preclinical technology to assess and monitor plaque
instability and thereby test potential plaque-stabilizing drugs. We suggest that
near-infrared autofluorescence imaging is a novel technology that allows
identification of atherosclerotic plaques with intraplaque hemorrhage and
ultimately holds promise for detection of high-risk plaques in
patients.Atherosclerosis diagnosis relies primarily on imaging and early
detection of high-risk atherosclerotic plaques is important for risk
stratification of patients and stabilization therapies. Here Htun et al.
demonstrate that vulnerable atherosclerotic plaques generate near-infrared
autofluorescence that can be detected via emission computed tomography.
PMID- 28706204
TI - Nanopatterning of steel by one-step anodization for anti-adhesion of bacteria.
AB - Surface nanopatterning of metals has been an effective technique for improved
performance and functionalization. However, it is of great challenge to fabricate
nanostructure on carbon steels despite their extensive use and urgent needs to
maintain the performance reliability and durability. Here, we report a one-step
anodization technique to nanopattern a carbon steel in 50 wt.% NaOH solution for
highly effective anti-adhesion by sulphate reducing bacteria (SRB), i.e.,
Desulfovibrio desulfuricans subsp. desulfuricans (Beijerinck) Kluyver and van
Niel. We characterize the morphology, structure, composition, and surface
roughness of the nanostructured film formed on the steel as a function of
anodizing potential. We quantify the surface hydrophobicity by contact angle
measurements, and the SRB adhesion by fluorescent analysis. The optimal
anodization potential of 2.0 V is determined for the best performance of anti
adhesion of SRB to the steel, resulting in a 23.5 times of reduction of SRB
adhesion compared to bare steel. We discuss the mechanisms for the film formation
on the steel during anodization, and the high-performance anti-adhesion of
bacteria to nanopatterned steels. Our technique is simple, cost-effective and
environment-friendly, providing a promising alternative for industry-scale
surface nanopatterning of carbon steels for effective controlling of bacterial
adhesion.
PMID- 28706205
TI - The alkaloids of Banisteriopsis caapi, the plant source of the Amazonian
hallucinogen Ayahuasca, stimulate adult neurogenesis in vitro.
AB - Banisteriopsis caapi is the basic ingredient of ayahuasca, a psychotropic plant
tea used in the Amazon for ritual and medicinal purposes, and by interested
individuals worldwide. Animal studies and recent clinical research suggests that
B. caapi preparations show antidepressant activity, a therapeutic effect that has
been linked to hippocampal neurogenesis. Here we report that harmine,
tetrahydroharmine and harmaline, the three main alkaloids present in B. caapi,
and the harmine metabolite harmol, stimulate adult neurogenesis in vitro. In
neurospheres prepared from progenitor cells obtained from the subventricular and
the subgranular zones of adult mice brains, all compounds stimulated neural stem
cell proliferation, migration, and differentiation into adult neurons. These
findings suggest that modulation of brain plasticity could be a major
contribution to the antidepressant effects of ayahuasca. They also expand the
potential application of B. caapi alkaloids to other brain disorders that may
benefit from stimulation of endogenous neural precursor niches.
PMID- 28706206
TI - Identification of long non-coding RNAs in two anthozoan species and their
possible implications for coral bleaching.
AB - Long non-coding RNAs (lncRNAs) have been shown to play regulatory roles in a
diverse range of biological processes and are associated with the outcomes of
various diseases. The majority of studies about lncRNAs focus on model organisms,
with lessened investigation in non-model organisms to date. Herein, we have
undertaken an investigation on lncRNA in two zoanthids (cnidarian):
Protolpalythoa varibilis and Palythoa caribaeorum. A total of 11,206 and 13,240
lncRNAs were detected in P. variabilis and P. caribaeorum transcriptome,
respectively. Comparison using NONCODE database indicated that the majority of
these lncRNAs is taxonomically species-restricted with no identifiable orthologs.
Even so, we found cases in which short regions of P. caribaeorum's lncRNAs were
similar to vertebrate species' lncRNAs, and could be associated with lncRNA
conserved regulatory functions. Consequently, some high-confidence lncRNA-mRNA
interactions were predicted based on such conserved regions, therefore revealing
possible involvement of lncRNAs in posttranscriptional processing and regulation
in anthozoans. Moreover, investigation of differentially expressed lncRNAs, in
healthy colonies and colonial individuals undergoing natural bleaching, indicated
that some up-regulated lncRNAs in P. caribaeorum could posttranscriptionally
regulate the mRNAs encoding proteins of Ras-mediated signal transduction pathway
and components of innate immune-system, which could contribute to the molecular
response of coral bleaching.
PMID- 28706207
TI - The influence of marital status on survival of gallbladder cancer patients: a
population-based study.
AB - Marital status has been found to be a prognostic factor for survival in various
cancers, but its role in gallbladder cancer (GBC) has not been fully studied. In
this study, we used the Surveillance, Epidemiology, and End Results Program
(SEER)-registered database to analyze the survival of GBC patients with different
marital status. A total of 6,627 GBC patients were selected from SEER database
from 2004 to 2013. The age, race, grade, histologic type, AJCC stage, SEER stage
and marital status were identified as independent prognostic factors. Married GBC
patients had a higher 5-year cancer-specific survival (CSS) than that of
unmarried ones (20.1% v.s. 17.8%, P < 0.05). Subgroup analyses showed that
widowed patients had 14.0% less of 5-year CSS compared to married ones of stage I
(55.9% v.s. 41.9%, P < 0.05), 14.7% of stage II (15.6% v.s. 10.9%, P < 0.05), and
1.5% of stage III + IV (2.9% v.s. 1.4%, P < 0.05). In addition, single is an
independent prognostic factor at stage III + IV (HR = 1.225, 95%CI 1.054-1.423, P
= 0.008). These results indicated that widowed patients were at a high risk of
cancer-specific mortality and marriage can be a protective prognostic factor in
CSS.
PMID- 28706208
TI - Predictability of state-level flood damage in the conterminous United States: the
role of hazard, exposure and vulnerability.
AB - Understanding historical changes in flood damage and the underlying mechanisms is
critical for predicting future changes for better adaptations. In this study, a
detailed assessment of flood damage for 1950-1999 is conducted at the state level
in the conterminous United States (CONUS). Geospatial datasets on possible
influencing factors are then developed by synthesizing natural hazards,
population, wealth, cropland and urban area to explore the relations with flood
damage. A considerable increase in flood damage in CONUS is recorded for the
study period which is well correlated with hazards. Comparably, runoff indexed
hazards simulated by the Variable Infiltration Capacity (VIC) model can explain a
larger portion of flood damage variations than precipitation in 84% of the
states. Cropland is identified as an important factor contributing to increased
flood damage in central US while urbanland exhibits positive and negative
relations with total flood damage and damage per unit wealth in 20 and 16 states,
respectively. Overall, flood damage in 34 out of 48 investigated states can be
predicted at the 90% confidence level. In extreme cases, ~76% of flood damage
variations can be explained in some states, highlighting the potential of future
flood damage prediction based on climate change and socioeconomic scenarios.
PMID- 28706209
TI - Mountain gorilla lymphocryptovirus has Epstein-Barr virus-like epidemiology and
pathology in infants.
AB - Epstein-Barr virus (EBV) infects greater than 90% of humans, is recognized as a
significant comorbidity with HIV/AIDS, and is an etiologic agent for some human
cancers. The critically endangered mountain gorilla population was suspected of
infection with an EBV-like virus based on serology and infant histopathology
similar to pulmonary reactive lymphoid hyperplasia (PRLH), a condition associated
with EBV in HIV-infected children. To further examine the presence of EBV or an
EBV-like virus in mountain gorillas, we conducted the first population-wide
survey of oral samples for an EBV-like virus in a nonhuman great ape. We
discovered that mountain gorillas are widely infected (n = 143/332) with a
specific strain of lymphocryptovirus 1 (GbbLCV-1). Fifty-two percent of infant
mountain gorillas were orally shedding GbbLCV-1, suggesting primary infection
during this stage of life, similar to what is seen in humans in less developed
countries. We then identified GbbLCV-1 in post-mortem infant lung tissues
demonstrating histopathological lesions consistent with PRLH, suggesting primary
infection with GbbLCV-1 is associated with PRLH in infants. Together, our
findings demonstrate that mountain gorilla's infection with GbbLCV-1 could
provide valuable information for human disease in a natural great ape setting and
have potential conservation implications in this critically endangered species.
PMID- 28706210
TI - Regulation of aromatase expression in the anterior amygdala of the developing
mouse brain depends on ERbeta and sex chromosome complement.
AB - During development sex differences in aromatase expression in limbic regions of
mouse brain depend on sex chromosome factors. Genes on the sex chromosomes may
affect the hormonal regulation of aromatase expression and this study was
undertaken to explore that possibility. Male E15 anterior amygdala neuronal
cultures expressed higher levels of aromatase (mRNA and protein) than female
cultures. Furthermore, treatment with oestradiol (E2) or dihydrotestosterone
(DHT) increased Cyp19a1 expression and aromatase protein levels only in female
neuronal cultures. The effect of E2 on aromatase expression was not imitated by
oestrogen receptor (ER) alpha agonist PPT or the GPER agonist G1, but it was
fully reproduced by DPN, a specific ligand of ERbeta. By contrast, the effect of
DHT on aromatase expression was not blocked by the anti-androgen flutamide, but
completely abrogated by the ERbeta antagonist PHTPP. Experiments using the four
core genotype model showed a sex chromosome effect in ERbeta expression (XY > XX)
and regulation by E2 or DHT (only XX respond) in amygdala neurons. In conclusion,
sex chromosome complement governs the hormonal regulation of aromatase expression
through activation of ERbeta in developing mouse brain.
PMID- 28706211
TI - Discovery of missing link between demosponges and hexactinellids confirms
palaeontological model of sponge evolution.
AB - The two major extant groups of siliceous sponges, Demospongiae and
Hexactinellida, are generally regarded as sister groups forming the clade
Silicea, although the nature of their last common ancestor is uncertain. The
fossil record contains a diverse range of basal demosponges that appear to have
evolved from hexactine-bearing reticulosan ancestors, although a compelling
morphological intermediate has not previously been discovered. Here we describe a
new species of fossil sponge, Conciliospongia anjiensis gen. et sp. nov., from
the Late Ordovician (~444 Ma) Anji Biota of South China. This species has a
reticulate, tufted skeleton of minute monaxon spicules, characteristic of the
fossil demosponge family Hazeliidae and modern heteroscleromorphs, with hexactine
spicules and a globose body form inherited from reticulosan ancestors. This
transitional morphology had previously been hypothesized in palaeontological
studies. This morphological intermediate between two extant classes further
confirms siliceous sponge monophyly and demosponge-hexactinellid spicule
homology, and supports the primitive, stem-silicean interpretation of simpler
structured fossil reticulosans.
PMID- 28706212
TI - Epigenetics of the preferential silencing of Brachypodium stacei-originated 35S
rDNA loci in the allotetraploid grass Brachypodium hybridum.
AB - Nucleolar dominance (ND), initially described as 'differential amphiplasty', is a
phenomenon observed in some plant and animal allopolyploids and hybrids in which
the selective suppression of the activity of 35S rRNA gene loci that have been
inherited from one of the two or more ancestral genomes occurs. Although more
than 80 years have passed since the discovery of ND, there is still a significant
lack in our understanding of the mechanisms that determine this phenomenon. Here,
we aimed to investigate the epigenetic status of 35S rRNA gene loci in the
monocotyledonous Brachypodium hybridum, which is an allotetraploid that has
resulted from a cross between B. distachyon and B. stacei. We revealed that the
repressed B. stacei-inherited rDNA loci are characterised by a high level of DNA
methylation. The global hypomethylation of B. hybridum nuclear DNA induced by 5
azacytidine, however, seems to be insufficient for the transcriptional
reactivation of these loci, which indicates that factors other than DNA
methylation are behind the suppression of B. stacei-originated loci. We also
showed that the transcriptionally active and silenced fractions of rRNA genes
that had been inherited from B. distachyon occupy different domains within the
chromocentres adjacent to the nucleolus, depending on their epigenetic status.
PMID- 28706213
TI - Transmission of highly virulent community-associated MRSA ST93 and livestock
associated MRSA ST398 between humans and pigs in Australia.
AB - Pigs have been recognised as a reservoir of livestock associated methicillin
resistant Staphylococcus aureus (LA-MRSA) in Europe, Asia and North America.
However, little is known about the presence and distribution of MRSA in the
Australian pig population and pig industry. This study describes the presence,
distribution and molecular characteristics of the human adapted Australian CA
MRSA ST93 isolated from pigs, people, and the environment within a piggery.
Isolates were subjected to antibiotic susceptibility testing, DNA microarray,
whole genome sequencing, multi locus sequence typing, virulence and resistance
gene characterization and phylogenetic analysis. MRSA were isolated from 60% (n =
52) of farm workers where 84% of isolates returned ST93 and the rest ST398. Of
the thirty-one pig isolates tested further, an equal number of ST398 and ST93 (15
each) and one as ST30-V were identified. Four of six environmental isolates were
identified as ST93 and two as ST398. This study has identified for the first time
in Australia the occurrence of CA-MRSA ST93 and LA-MRSA ST398 amongst farm
workers, pigs, and the farm environment. Comparative genome analysis indicates
that ST398 is likely to have been introduced into Australia from Europe or North
America. This study also reports the first linezolid resistant MRSA isolated in
Australia.
PMID- 28706214
TI - Transcriptome Analysis of Three Sheep Intestinal Regions reveals Key Pathways and
Hub Regulatory Genes of Large Intestinal Lipid Metabolism.
AB - The large intestine, also known as the hindgut, is an important part of the
animal digestive system. Recent studies on digestive system development in
ruminants have focused on the rumen and the small intestine, but the molecular
mechanisms underlying sheep large intestine metabolism remain poorly understood.
To identify genes related to intestinal metabolism and to reveal molecular
regulation mechanisms, we sequenced and compared the transcriptomes of mucosal
epithelial tissues among the cecum, proximal colon and duodenum. A total of 4,221
transcripts from 3,254 genes were identified as differentially expressed
transcripts. Between the large intestine and duodenum, differentially expressed
transcripts were found to be significantly enriched in 6 metabolism-related
pathways, among which PPAR signaling was identified as a key pathway. Three
genes, CPT1A, LPL and PCK1, were identified as higher expression hub genes in the
large intestine. Between the cecum and colon, differentially expressed
transcripts were significantly enriched in 5 lipid metabolism related pathways,
and CEPT1 and MBOAT1 were identified as hub genes. This study provides important
information regarding the molecular mechanisms of intestinal metabolism in sheep
and may provide a basis for further study.
PMID- 28706215
TI - Synthetic-lattice enabled all-optical devices based on orbital angular momentum
of light.
AB - All-optical photonic devices are crucial for many important photonic technologies
and applications, ranging from optical communication to quantum information
processing. Conventional design of all-optical devices is based on photon
propagation and interference in real space, which may rely on large numbers of
optical elements, and the requirement of precise control makes this approach
challenging. Here we propose an unconventional route for engineering all-optical
devices using the photon's internal degrees of freedom, which form photonic
crystals in such synthetic dimensions for photon propagation and interference. We
demonstrate this design concept by showing how important optical devices such as
quantum memory and optical filters can be realized using synthetic orbital
angular momentum (OAM) lattices in degenerate cavities. The design route
utilizing synthetic photonic lattices may significantly reduce the requirement
for numerous optical elements and their fine tuning in conventional design,
paving the way for realistic all-optical photonic devices with novel
functionalities.
PMID- 28706216
TI - Highly efficient multicolor multifocus microscopy by optimal design of
diffraction binary gratings.
AB - Multifocus microscopy (MFM) allows sensitive and fast three-dimensional imaging.
It relies on the efficient design of diffraction phase gratings yielding
homogeneous intensities in desired diffraction orders. Such performances are
however guaranteed only for a specific wavelength. Here, we discuss a novel
approach for designing binary phase gratings with dual color properties and
improved diffraction efficiency for MFM. We simulate binary diffraction gratings
with tunable phase shifts to explore its best diffraction performances. We report
the design and fabrication of a binary array generator of 3 * 3 equal-intensity
diffraction orders with 74% efficiency, 95% uniformity and dual color capability.
The multicolor properties of this new design are highlighted by two-color MFM
imaging. Finally, we discuss the basics of extending this approach to a variety
of diffraction pattern designs.
PMID- 28706217
TI - Oscillatory Nernst effect in Pt|ferrite|cuprate-superconductor trilayer films.
AB - Although magnetism and superconductivity hardly coexist in a single material,
recent advances in nanotechnology and spintronics have brought to light their
interplay in magnetotransport in thin-film heterostructures. Here, we found a
periodic oscillation of Nernst voltage with respect to magnetic fields in
Pt|LiFe5O8 (Pt|LFO) bilayers grown on a cuprate superconductor YBa2Cu3O7-x
(YBCO). At high temperatures above the superconducting transition temperature (T
C ) of YBCO, spin Seebeck voltages originating in Pt|LFO layers are observed. As
temperature decreases well below T C , the spin Seebeck voltage is suppressed and
unconventional periodic voltage oscillation as a function of magnetic fields
appears; such an oscillation emerging along the Hall direction in the
superconducting state has not been observed yet. Dynamics of superconducting
vortices pinned by surface precipitates seems responsible for the oscillatory
Nernst effect.
PMID- 28706218
TI - Patch clamp-assisted single neuron lipidomics.
AB - Our understanding of the physiological and pathological functions of brain lipids
is limited by the inability to analyze these molecules at cellular resolution.
Here, we present a method that enables the detection of lipids in identified
single neurons from live mammalian brains. Neuronal cell bodies are captured from
perfused mouse brain slices by patch clamping, and lipids are analyzed using an
optimized nanoflow liquid chromatography/mass spectrometry protocol. In a first
application of the method, we identified more than 40 lipid species from dentate
gyrus granule cells and CA1 pyramidal neurons of the hippocampus. This survey
revealed substantial lipid profile differences between neurons and whole brain
tissue, as well as between resting and physiologically stimulated neurons. The
results suggest that patch clamp-assisted single neuron lipidomics could be
broadly applied to investigate neuronal lipid homeostasis in healthy and diseased
brains.
PMID- 28706219
TI - High temperature-induced production of unreduced pollen and its cytological
effects in Populus.
AB - Temperature change is of potential to trigger the formation of unreduced gametes.
In this study, we showed that short periods of high temperature treatment can
induce the production of 2n pollen in Populus pseudo-simonii Kitag. The meiotic
stage, duration of treatment, and temperature have significant effects on the
induction of 2n pollen. Heat stress resulted in meiotic abnormalities, including
failure of chromosome separation, chromosome stickiness, laggards and
micronuclei. Spindle disorientations in the second meiotic division, such as
parallel, fused, and tripolar spindles, either increased in frequency or were
induced de novo by high temperature treatment. We found that the high temperature
treatment induced depolymerisation of meiotic microtubular cytoskeleton,
resulting in the failure of chromosome segregation. New microtubular
cytoskeletons were able to repolymerise in some heat-treated cells after
transferring them to normal conditions. However, aberrant cytokinesis occurred
owing to defects of new radial microtubule systems, leading to production of
monads, dyads, triads, and polyads. This suggested that depolymerisation and
incomplete restoration of microtubules may be important for high temperature
induction of unreduced gametes. These findings might help us understand how
polyploidisation is induced by temperature-related stress and support the
potential effects of global climate change on reproductive development of plants.
PMID- 28706221
TI - CCL11, a novel mediator of inflammatory bone resorption.
AB - Normal bone homeostasis, which is regulated by bone-resorbing osteoclasts and
bone-forming osteoblasts is perturbed by inflammation. In chronic inflammatory
disease with disturbed bone remodelling, e.g. rheumatoid arthritis, patients show
increased serum levels of the chemokine eotaxin-1 (CCL11). Herein, we demonstrate
an inflammatory driven expression of CCL11 in bone tissue and a novel role of
CCL11 in osteoclast migration and resorption. Using an inflammatory bone lesion
model and primary cell cultures, we discovered that osteoblasts express CCL11 in
vivo and in vitro and that expression increased during inflammatory conditions.
Osteoclasts did not express CCL11, but the high affinity receptor CCR3 was
significantly upregulated during osteoclast differentiation and found to
colocalise with CCL11. Exogenous CCL11 was internalised in osteoclast and
stimulated the migration of pre-osteoclast and concomitant increase in bone
resorption. Our data pinpoints that the CCL11/CCR3 pathway could be a new target
for treatment of inflammatory bone resorption.
PMID- 28706222
TI - Urinary 6-sulfatoxymelatonin level and breast cancer risk: systematic review and
meta-analysis.
AB - 6-Sulfatoxymelatonin (aMT6s) is the main metabolite of melatonin in urine, and is
a reliable surrogate biomarker reflecting the blood melatonin concentration. This
meta-analysis assessed the association between urinary aMT6s level and BC
incidence. The electronic databases PubMed, EMBASE, Cochrane Library, and Web of
Science were searched. Risk ratios (RRs) were adopted to estimate the relative BC
incidence. A total of 7 prospective case-control publications were included, and
6 of them were distinct studies. Pooled analysis of data from the 6 studies
involving 1824 women with incident BC and 3954 matched control participants with
no overlapping of subjects among studies indicated no significant association
between the highest levels of urinary aMT6s and the incidence of BC (RR = 0.97,
95% CI, 0.88-1.08, P = 0.56). Negative associations were observed in
postmenopausal women (RR = 0.88, 95% CI, 0.75-1.02, P = 0.10), estrogen receptor
positive BC (RR = 0.83, 95% CI, 0.64-1.07, P = 0.15), and studies using 12-hour
overnight urine (RR = 0.81, 95% CI, 0.61-1.07, P = 0.13), all with borderline
significances. Lag time or invasive degree did not interfere with the results.
There was no evident publication bias detected by the Egger's test and the funnel
plot. Conclusively, the current evidence did not support a significant
association between urinary aMT6s level and BC risk.
PMID- 28706220
TI - Opportunities for therapeutic antibodies directed at G-protein-coupled receptors.
AB - G-protein-coupled receptors (GPCRs) are activated by a diverse range of ligands,
from large proteins and proteases to small peptides, metabolites,
neurotransmitters and ions. They are expressed on all cells in the body and have
key roles in physiology and homeostasis. As such, GPCRs are one of the most
important target classes for therapeutic drug discovery. The development of drugs
targeting GPCRs has therapeutic value across a wide range of diseases, including
cancer, immune and inflammatory disorders as well as neurological and metabolic
diseases. The progress made by targeting GPCRs with antibody-based therapeutics,
as well as technical hurdles to overcome, are presented and discussed in this
Review. Antibody therapeutics targeting C-C chemokine receptor type 4 (CCR4),
CCR5 and calcitonin gene-related peptide (CGRP) are used as illustrative clinical
case studies.
PMID- 28706223
TI - Single molecule magnet with an unpaired electron trapped between two lanthanide
ions inside a fullerene.
AB - Increasing the temperature at which molecules behave as single-molecule magnets
is a serious challenge in molecular magnetism. One of the ways to address this
problem is to create the molecules with strongly coupled lanthanide ions. In this
work, endohedral metallofullerenes Y2@C80 and Dy2@C80 are obtained in the form of
air-stable benzyl monoadducts. Both feature an unpaired electron trapped between
metal ions, thus forming a single-electron metal-metal bond. Giant exchange
interactions between lanthanide ions and the unpaired electron result in single
molecule magnetism of Dy2@C80(CH2Ph) with a record-high 100 s blocking
temperature of 18 K. All magnetic moments in Dy2@C80(CH2Ph) are parallel and
couple ferromagnetically to form a single spin unit of 21 MUB with a dysprosium
electron exchange constant of 32 cm-1. The barrier of the magnetization reversal
of 613 K is assigned to the state in which the spin of one Dy centre is flipped.
PMID- 28706224
TI - Postglacial range expansion and the role of ecological factors in driving
adaptive evolution of Musa basjoo var. formosana.
AB - Genetic variation evolves during postglacial range expansion of a species and is
important for adapting to varied environmental conditions. It is crucial for the
future survival of a species. We investigate the nuclear DNA sequence variation
to provide evidence of postglacial range expansion of Musa basjoo var. formosana,
a wild banana species, and test for adaptive evolution of amplified fragment
length polymorphic (AFLP) loci underlying local adaptation in association with
environmental variables. Postglacial range expansion was suggested by
phylogeographical analyses based on sequence variation of the second intron of
copper zinc superoxide dismutase 2 gene. Two glacial refugia were inferred by the
average F ST parameter (mean F ST of a population against the remaining
populations). Using variation partitioning by redundancy analysis, we found a
significant amount of explained AFLP variation attributed to environmental and
spatially-structured environmental effects. By combining genome scan methods and
multiple univariate logistic regression, four AFLP loci were found to be strongly
associated with environmental variables, including temperature, precipitation,
soil moisture, wet days, and surface coverage activity representing vegetation
greenness. These environmental variables may have played various roles as
ecological drivers for adaptive evolution of M. basjoo var. formosana during
range expansion after the last glacial maximum.
PMID- 28706225
TI - Climate change impacts on the threatened terrestrial vertebrates of the Pacific
Islands.
AB - The aim of this study was to undertake a broad-scale understanding of the
distribution of vulnerable, endangered and critically endangered terrestrial
vertebrate species in the Pacific and the assessment of impacts of climate change
and sea level rise. 150 critically endangered, endangered and vulnerable
terrestrial vertebrates found in 23 countries of the Pacific were linked to
island susceptibility to climate change. Out of the 1779 islands making up the 23
countries, 674 of them hosted at least one species from the above categories. 84
of the 150 species are endemic to this study area and many of these occur on
islands with high susceptibility to climate change, with many of them occurring
on one island only. The species data, together with islands, was overlain with
Mean Significant Wave Height (Hs) projections for 2081-2100 under RCP4.5 and 8.5,
and further analysed for threat of extinction. A large number of critically
endangered and endangered species fall in regions that have the highest Hs
projections.
PMID- 28706226
TI - Reactogenicity to major tuberculosis antigens absent in BCG is linked to improved
protection against Mycobacterium tuberculosis.
AB - MTBVAC is a live-attenuated Mycobacterium tuberculosis vaccine, currently under
clinical development, that contains the major antigens ESAT6 and CFP10. These
antigens are absent from the current tuberculosis vaccine, BCG. Here we compare
the protection induced by BCG and MTBVAC in several mouse strains that naturally
express different MHC haplotypes differentially recognizing ESAT6 and CFP10.
MTBVAC induces improved protection in C3H mice, the only of the three tested
strains reactive to both ESAT6 and CFP10. Deletion of both antigens in MTBVAC
reduces its efficacy to BCG levels, supporting a link between greater efficacy
and CFP10- and ESAT6-specific reactogenicity. In addition, MTBVAC (but not BCG)
triggers a specific response in human vaccinees against ESAT6 and CFP10. Our
results warrant further exploration of this response as potential biomarker of
protection in MTBVAC clinical trials.
PMID- 28706227
TI - Phenomenological Model for Defect Interactions in Irradiated Functional
Materials.
AB - The ability to tailor the performance of functional materials, such as
semiconductors, via careful manipulation of defects has led to extraordinary
advances in microelectronics. Functional metal oxides are no exception - protonic
defect-conducting oxides find use in solid oxide fuel cells (SOFCs) and oxygen
deficient high-temperature superconductors are poised for power transmission and
magnetic imaging applications. Similarly, the advantageous functional responses
in ferroelectric materials that make them attractive for use in
microelectromechanical systems (MEMS), logic elements, and environmental energy
harvesting, are derived from interactions of defects with other defects (such as
domain walls) and with the lattice. Chemical doping has traditionally been
employed to study the effects of defects in functional materials, but
complications arising from compositional heterogeneity often make interpretation
of results difficult. Alternatively, irradiation is a versatile means of
evaluating defect interactions while avoiding the complexities of doping. Here, a
generalized phenomenological model is developed to quantify defect interactions
and compare material performance in functional oxides as a function of radiation
dose. The model is demonstrated with historical data from literature on
ferroelectrics, and expanded to functional materials for SOFCs, mixed ionic
electronic conductors (MIECs), He-ion implantation, and superconductors.
Experimental data is used to study microstructural effects on defect interactions
in ferroelectrics.
PMID- 28706228
TI - Analysing the natural population growth of a large marine mammal after a
depletive harvest.
AB - An understanding of the underlying processes and comprehensive history of
population growth after a harvest-driven depletion is necessary when assessing
the long-term effectiveness of management and conservation strategies. The South
American sea lion (SASL), Otaria flavescens, is the most conspicuous marine
mammal along the South American coasts, where it has been heavily exploited. As a
consequence of this exploitation, many of its populations were decimated during
the early 20th century but currently show a clear recovery. The aim of this study
was to assess SASL population recovery by applying a Bayesian state-space
modelling framework. We were particularly interested in understanding how the
population responds at low densities, how human-induced mortality interplays with
natural mechanisms, and how density-dependence may regulate population growth.
The observed population trajectory of SASL shows a non-linear relationship with
density, recovering with a maximum increase rate of 0.055. However, 50 years
after hunting cessation, the population still represents only 40% of its pre
exploitation abundance. Considering that the SASL population in this region
represents approximately 72% of the species abundance within the Atlantic Ocean,
the present analysis provides insights into the potential mechanisms regulating
the dynamics of SASL populations across the global distributional range of the
species.
PMID- 28706229
TI - Quantitative interactome of a membrane Bcl-2 network identifies a hierarchy of
complexes for apoptosis regulation.
AB - The Bcl-2 proteins form a complex interaction network that controls mitochondrial
permeabilization and apoptosis. The relative importance of different Bcl-2
complexes and their spatio-temporal regulation is debated. Using fluorescence
cross-correlation spectroscopy to quantify the interactions within a minimal Bcl
2 network, comprised by cBid, Bax, and Bcl-xL, we show that membrane insertion
drastically alters the pattern of Bcl-2 complexes, and that the C-terminal helix
of Bcl-xL determines its binding preferences. At physiological temperature, Bax
can spontaneously activate in a self-amplifying process. Strikingly, Bax also
recruits Bcl-xL to membranes, which is sufficient to retrotranslocate Bax back
into solution to secure membrane integrity. Our study disentangles the hierarchy
of Bcl-2 complex formation in relation to their environment: Bcl-xL association
with cBid occurs in solution and in membranes, where the complex is stabilized,
whereas Bcl-xL binding to Bax occurs only in membranes and with lower affinity
than to cBid, leading instead to Bax retrotranslocation.The permeabilization of
the mitochondrial outer membrane to induce apoptosis is regulated by complex
interactions between Bcl-2 family members. Here the authors develop a
quantitative interactome of a membrane Bcl-2 network and identify a hierarchy of
protein complexes in apoptosis induction.
PMID- 28706230
TI - Semiconductor-based Multilayer Selective Solar Absorber for Unconcentrated Solar
Thermal Energy Conversion.
AB - Solar thermal energy conversion has attracted substantial renewed interest due to
its applications in industrial heating, air conditioning, and electricity
generation. Achieving stagnation temperatures exceeding 200 degrees C, pertinent
to these technologies, with unconcentrated sunlight requires spectrally selective
absorbers with exceptionally low emissivity in the thermal wavelength range and
high visible absorptivity for the solar spectrum. In this Communication, we
report a semiconductor-based multilayer selective absorber that exploits the
sharp drop in optical absorption at the bandgap energy to achieve a measured
absorptance of 76% at solar wavelengths and a low emittance of approximately 5%
at thermal wavelengths. In field tests, we obtain a peak temperature of 225
degrees C, comparable to that achieved with state-of-the-art selective surfaces.
With straightforward optimization to improve solar absorption, our work shows the
potential for unconcentrated solar thermal systems to reach stagnation
temperatures exceeding 300 degrees C, thereby eliminating the need for solar
concentrators for mid-temperature solar applications such as supplying process
heat.
PMID- 28706231
TI - Multiple Ligand-Bound States of a Phosphohexomutase Revealed by Principal
Component Analysis of NMR Peak Shifts.
AB - Enzymes sample multiple conformations during their catalytic cycles. Chemical
shifts from Nuclear Magnetic Resonance (NMR) are hypersensitive to conformational
changes and ensembles in solution. Phosphomannomutase/phosphoglucomutase
(PMM/PGM) is a ubiquitous four-domain enzyme that catalyzes phosphoryl transfer
across phosphohexose substrates. We compared states the enzyme visits during its
catalytic cycle. Collective responses of Pseudomonas PMM/PGM to phosphosugar
substrates and inhibitor were assessed using NMR-detected titrations. Affinities
were estimated from binding isotherms obtained by principal component analysis
(PCA). Relationships among phosphosugar-enzyme associations emerge from PCA
comparisons of the titrations. COordiNated Chemical Shifts bEhavior (CONCISE)
analysis provides novel discrimination of three ligand-bound states of PMM/PGM
harboring a mutation that suppresses activity. Enzyme phosphorylation and
phosphosugar binding appear to drive the open dephosphorylated enzyme to the free
phosphorylated state, and on toward ligand-closed states. Domain 4 appears
central to collective responses to substrate and inhibitor binding. Hydrogen
exchange reveals that binding of a substrate analogue enhances folding stability
of the domains to a uniform level, establishing a globally unified structure.
CONCISE and PCA of NMR spectra have discovered novel states of a well-studied
enzyme and appear ready to discriminate other enzyme and ligand binding states.
PMID- 28706232
TI - Self-Organized Micro-Spiral of Single-Walled Carbon Nanotubes.
AB - Single-walled carbon nanotubes (SWCNTs) are reported to spontaneously align in a
rotational pattern by drying a liquid droplet of toluene containing polyfluorene
as a dispersant. By situating a droplet of an SWCNT solution around a glass bead,
spiral patterns are generated. The parallel alignment of SWCNTs along one stripe
of such a pattern is confirmed using scanning electron microscopy and polarized
optical microscopy. The orientation order increases toward the outer edge of a
stripe. The stripe width in the pattern is proportional to the solute
concentration, and the width and position of the stripes follow geometric
sequences. The growth of the rotational pattern is also observed in real time.
The process of spiral pattern formation is visualized, indicating the role of the
annihilation of counter-traveling accompanied by continuous depinning. The
geometric sequences for the stripe width and position are explained by the near
constant traveling speed and solute enrichment at the droplet periphery.
PMID- 28706233
TI - Dome-like behaviour at Mt. Etna: The case of the 28 December 2014 South East
Crater paroxysm.
AB - On the 28 December 2014, a violent and short paroxysmal eruption occurred at the
South East Crater (SEC) of Mount Etna that led to the formation of huge niches on
the SW and NE flanks of the SEC edifice from which a volume of ~3 * 106 m3 of
lava was erupted. Two basaltic lava flows discharged at a rate of ~370 m3/s,
reaching a maximum distance of ~5 km. The seismicity during the event was scarce
and the eruption was not preceded by any notable ground deformation, which
instead was dramatic during and immediately after the event. The SO2 flux
associated with the eruption was relatively low and even decreased few days
before. Observations suggest that the paroxysm was not related to the ascent of
volatile-rich fresh magma from a deep reservoir (dyke intrusion), but instead to
a collapse of a portion of SEC, similar to what happens on exogenous andesitic
domes. The sudden and fast discharge eventually triggered a depressurization in
the shallow volcano plumbing system that drew up fresh magma from depth.
Integration of data and observations has allowed to formulate a novel
interpretation of mechanism leading volcanic activity at Mt. Etna and on basaltic
volcanoes worldwide.
PMID- 28706234
TI - Investigation of brain tissue infiltration by medulloblastoma cells in an ex vivo
model.
AB - Medulloblastoma (MB) is a paediatric cancer of the cerebellum that can develop
cerebellar and leptomeningeal metastases. Local brain tissue infiltration, the
underlying cause of metastasis and relapse, remains unexplored. We developed a
novel approach to investigate tissue infiltration of MB using organotypic
cerebellum slice culture (OCSC). We show that cellular and structural components
of cerebellar tissue in OCSCs are maintained for up to 30 days ex vivo, and that
OCSCs foster tumour growth and cell proliferation. Using cell-based models of
sonic hedgehog (SHH) and group 3 (G3) MB, we quantified tumour growth and
infiltration and determined the morphological characteristics of the infiltrating
cells. We observed basal levels of dissemination occurring in both subgroups with
cells migrating either individually or collectively as clusters. Collective
cerebellar tissue infiltration of SHH MB cells was further enhanced by EGF but
not HGF, demonstrating differential tumour cell responses to microenvironmental
cues. We found G3 cells to be hyper proliferative and observed aggressive tumour
expansion even in the absence of exogenous growth factors. Our study thus
provides unprecedented insights into brain tissue infiltration of SHH and G3 MB
cells and reveals the cellular basis of the tumour progressing functions of EGF
in SHH MB.
PMID- 28706235
TI - Temporal profiles for measuring threshold of random lasers pumped by ns pulses.
AB - The working threshold is an important parameter to assess the performance of
cavity-free random lasers. Here, the temporal profile measurement is proposed as
an alternative method to determine the thresholds of the surface plasmon based
random lasers pumped by ns pulses based on analyzing the delay time (t Delay) and
rising time (t R) of the emission signal. The obvious and slight inflection
points of the curves of t Delay and t R varying with the pump power density are
observed as indicators for the thresholds of random lasing and for the transition
of lasing mode, respectively. The proposed method supplies consistent values to
those supplied by traditional methods in frequency-domain for the random systems
with different gain length. The demonstrated temporal profile approaches are free
from the spectrometers and may be as a candidate for measuring the threshold of
random lasers in ultrafast optics, nonlinear optics and bio-compatible
optoelectronic probes.
PMID- 28706236
TI - Metabolomic differential analysis of interspecific interactions among white rot
fungi Trametes versicolor, Dichomitus squalens and Pleurotus ostreatus.
AB - Interspecific fungal antagonism occurred commonly in the interaction zone of
different white rot fungi. This competitive interaction could markedly influence
the metabolic pathway of intracellular metabolites, which was associated with the
fungal morphology change and growth restriction. So far, it remains unknown on
intracellular metabolite regulation during fungal competitive interaction.
Herein, we performed the metabolomic analysis of the in vivo metabolite changes
during competitive interaction between each two of the three white rot fungi
Trametes versicolor, Pleurotus ostreatus and Dichomitus squalens and identified
differential metabolites in the interaction zone compared to each two isolates.
Many metabolites in the carnitine, lipid, ethylene and trehalose metabolic
pathways were significantly up-regulated. These metabolic pathways are all
involved in defensive response to abiotic and/or biotic stressful condition.
PMID- 28706237
TI - Suppressed autophagic response underlies augmentation of renal
ischemia/reperfusion injury by type 2 diabetes.
AB - Diabetes mellitus is a major risk factor for acute kidney injury (AKI). Here, we
hypothesized that suppression of autophagic response underlies aggravation of
renal ischemia/reperfusion (I/R) injury by type 2 diabetes mellitus (T2DM). In
OLETF, a rat model of T2DM, and its non-diabetic control, LETO, AKI was induced
by unilateral nephrectomy and 30-min occlusion and 24-h reperfusion of the renal
artery in the contralateral kidney. Levels of serum creatinine and blood urea
nitrogen and tubular injury score after I/R were significantly higher in OLETF
than in LETO. Administration of chloroquine, a widely used autophagy inhibitor,
aggravated I/R-induced renal injury in LETO, but not in OLETF. In contrast to
LETO, OLETF exhibited no increase in autophagosomes in the proximal tubules after
I/R. Immunoblotting showed that I/R activated the AMPK/ULK1 pathway in LETO but
not in OLETF, and mTORC1 activation after I/R was enhanced in OLETF. Treatment of
OLETF with rapamycin, an mTORC1 inhibitor, partially restored autophagic
activation in response to I/R and significantly attenuated I/R-induced renal
injury. Collectively, these findings indicate that suppressed autophagic
activation in proximal tubules by impaired AMPK/ULK1 signaling and upregulated
mTORC1 activation underlies T2DM-induced worsening of renal I/R injury.
PMID- 28706238
TI - Freezing response-independent facilitation of fear extinction memory in the
prefrontal cortex.
AB - The infralimbic cortex (IL) is known to facilitate the formation of extinction
memory through reciprocal interactions with the amygdala, which produces fear
responses such as freezing. Thus, whether presynaptic input from the amygdala and
post-synaptic output of IL neurons are functionally dissociated in extinction
memory formation remains unclear. Here, we demonstrated that photostimulation of
IL inputs from BLA did not change freezing responses to conditioned stimuli (CS)
during training, but did facilitate extinction memory, measured as a reduction in
freezing responses to the CS 1 day later. On the other hand, photostimulation of
somata of IL neurons induced an immediate reduction in freezing to CS, but this
did not affect extinction memory tested the next day. These results provide in
vivo evidence for IL-dependent facilitation of extinction memory without post
synaptic modulation of freezing circuits.
PMID- 28706239
TI - Increased adipose tissue heme levels and exportation are associated with altered
systemic glucose metabolism.
AB - Iron status is known to be associated with the physiology of adipose tissue (AT).
We aimed to investigate AT heme and expression of heme exporter (FLVCR1) in
association with obesity and type 2 diabetes (T2D). Substantial amounts of FLVCR1
mRNA and protein levels were detected in AT, being significantly increased in
subjects with T2D, and positively correlated with fasting glucose, fasting
triglycerides and with circulating markers of iron stores (serum ferritin, blood
hemoglobin and hematocrit). In both visceral (VAT) and subcutaneous AT (SAT),
increased heme levels were found in subjects with T2D. Reinforcing these
associations, FLVCR1 mRNA levels were positively linked to fasting glucose in an
independent cohort. Longitudianlly, the percent change of FLVCR1 positively
correlated with the percent change in fasting glucose (r = 0.52, p = 0.03) after
bariatric surgery-induced weight loss. High-fat diet-induced weight gain in rats
did not result in significant changes in AT Flvcr1 mRNA but, remarkably, the
expression of this gene positively correlated with fasting glucose and negatively
with insulin sensitivity (QUICKI). Altogether, these findings showed a direct
association between FLVCR1 mRNA levels and hyperglycemia, suggesting that
increased adipose tissue heme exportation might disrupt, or is the consequence
of, impaired systemic glucose metabolism during the progression to T2D.
PMID- 28706240
TI - Gasoline cars produce more carbonaceous particulate matter than modern filter
equipped diesel cars.
AB - Carbonaceous particulate matter (PM), comprising black carbon (BC), primary
organic aerosol (POA) and secondary organic aerosol (SOA, from atmospheric aging
of precursors), is a highly toxic vehicle exhaust component. Therefore,
understanding vehicle pollution requires knowledge of both primary emissions, and
how these emissions age in the atmosphere. We provide a systematic examination of
carbonaceous PM emissions and parameterisation of SOA formation from modern
diesel and gasoline cars at different temperatures (22, -7 degrees C) during
controlled laboratory experiments. Carbonaceous PM emission and SOA formation is
markedly higher from gasoline than diesel particle filter (DPF) and catalyst
equipped diesel cars, more so at -7 degrees C, contrasting with nitrogen oxides
(NOX). Higher SOA formation from gasoline cars and primary emission reductions
for diesels implies gasoline cars will increasingly dominate vehicular total
carbonaceous PM, though older non-DPF-equipped diesels will continue to dominate
the primary fraction for some time. Supported by state-of-the-art source
apportionment of ambient fossil fuel derived PM, our results show that whether
gasoline or diesel cars are more polluting depends on the pollutant in question,
i.e. that diesel cars are not necessarily worse polluters than gasoline cars.
PMID- 28706241
TI - Abnormal Paraventricular Nucleus of Hypothalamus and Growth Retardation
Associated with Loss of Nuclear Receptor Gene COUP-TFII.
AB - The paraventricular nucleus of hypothalamus plays important roles in the
regulation of energy balance and fetal growth. However, the molecular mechanisms
underlying its formation and function have not been clearly elucidated. Various
mutations in the human COUP-TFII gene, which encodes a nuclear receptor, result
in growth retardation, congenital diaphragmatic hernia and congenital heart
defects. Here, we show that COUP-TFII gene is expressed in the developing
hypothalamus in mouse. The ventral forebrain-specific RXCre/+; COUP-TFII F/F
mutant mice display growth retardation. The development of the paraventricular
nucleus of hypothalamus is compromised in the COUP-TFII mutant mainly because of
increased apoptosis and mis-migration of the Brn2+ neurons. Moreover, hypoplastic
anterior pituitary with blood cell clusters and shrunken posterior pituitary
lacking AVP/OT neuron innervations are observed in the mutant, indicating the
failure of formation of the hypothalamic-pituitary axis. Mechanistic studies show
that the expression of Bdnf and Nrp1 genes is reduced in the mutant embryo, and
that Bdnf is a direct downstream target of the COUP-TFII protein. Thus, our
findings provide a novel functional validation that COUP-TFII gene promotes the
expression of Bdnf and Nrp1 genes to ensure the appropriate morphogenesis of the
hypothalamic-pituitary axis, especially the paraventricular nucleus of
hypothalamus, and to prevent growth retardation.
PMID- 28706242
TI - Draft whole genome sequence of groundnut stem rot fungus Athelia rolfsii
revealing genetic architect of its pathogenicity and virulence.
AB - Groundnut (Arachis hypogaea L.) is an important oil seed crop having major biotic
constraint in production due to stem rot disease caused by fungus, Athelia
rolfsii causing 25-80% loss in productivity. As chemical and biological combating
strategies of this fungus are not very effective, thus genome sequencing can
reveal virulence and pathogenicity related genes for better understanding of the
host-parasite interaction. We report draft assembly of Athelia rolfsii genome of
~73 Mb having 8919 contigs. Annotation analysis revealed 16830 genes which are
involved in fungicide resistance, virulence and pathogenicity along with putative
effector and lethal genes. Secretome analysis revealed CAZY genes representing
1085 enzymatic genes, glycoside hydrolases, carbohydrate esterases, carbohydrate
binding modules, auxillary activities, glycosyl transferases and polysaccharide
lyases. Repeat analysis revealed 11171 SSRs, LTR, GYPSY and COPIA elements.
Comparative analysis with other existing ascomycotina genome predicted conserved
domain family of WD40, CYP450, Pkinase and ABC transporter revealing insight of
evolution of pathogenicity and virulence. This study would help in understanding
pathogenicity and virulence at molecular level and development of new combating
strategies. Such approach is imperative in endeavour of genome based solution in
stem rot disease management leading to better productivity of groundnut crop in
tropical region of world.
PMID- 28706243
TI - Target guided synthesis using DNA nano-templates for selectively assembling a G
quadruplex binding c-MYC inhibitor.
AB - The development of small molecules is essential to modulate the cellular
functions of biological targets in living system. Target Guided Synthesis (TGS)
approaches have been used for the identification of potent small molecules for
biological targets. We herein demonstrate an innovative example of TGS using DNA
nano-templates that promote Huisgen cycloaddition from an array of azide and
alkyne fragments. A G-quadruplex and a control duplex DNA nano-template have been
prepared by assembling the DNA structures on gold-coated magnetic nanoparticles.
The DNA nano-templates facilitate the regioselective formation of 1,4-substituted
triazole products, which are easily isolated by magnetic decantation. The G
quadruplex nano-template can be easily recovered and reused for five reaction
cycles. The major triazole product, generated by the G-quadruplex inhibits c-MYC
expression by directly targeting the c-MYC promoter G-quadruplex. This work
highlights that the nano-TGS approach may serve as a valuable strategy to
generate target-selective ligands for drug discovery.
PMID- 28706244
TI - Predicting Magnetostimulation Thresholds in the Peripheral Nervous System using
Realistic Body Models.
AB - Rapid switching of applied magnetic fields in the kilohertz frequency range in
the human body induces electric fields powerful enough to cause Peripheral Nerve
Stimulation (PNS). PNS has become one of the main constraints on the use of high
gradient fields for fast imaging with the latest MRI gradient technology. In
recent MRI gradients, the applied fields are powerful enough that PNS limits
their application in fast imaging sequences like echo-planar imaging. Application
of Magnetic Particle Imaging (MPI) to humans is similarly PNS constrained.
Despite its role as a major constraint, PNS considerations are only indirectly
incorporated in the coil design process, mainly through using the size of the
linear region as a proxy for PNS thresholds or by conducting human experiments
after constructing coil prototypes. We present for the first time, a framework to
simulate PNS thresholds for realistic coil geometries to directly address PNS in
the design process. Our PNS model consists of an accurate body model for
electromagnetic field simulations, an atlas of peripheral nerves, and a
neurodynamic model to predict the nerve responses to imposed electric fields.
With this model, we were able to reproduce measured PNS thresholds of two leg/arm
solenoid coils with good agreement.
PMID- 28706245
TI - Connexin 50 Functions as an Adhesive Molecule and Promotes Lens Cell
Differentiation.
AB - Connexins play essential roles in lens homeostasis and development. Here, we
identified a new role for Cx50 that mediates cell-cell adhesion function. Cx50
enhanced the adhesive capability of AQP0. Interestingly, the expression of Cx50
alone promoted cell adhesion at a comparable level to AQP0; however, this cell
adhesive function was not observed with other lens connexins, Cx43 and Cx46.
Moreover, the adhesive property occurred in both homotypic with Cx50 expressed in
both pairing cells and heterotypic with Cx50 in only one pairing cell, and this
function appears to be unrelated to its role in forming gap junction channels.
Cx50 KO lenses exhibited increased intercellular spaces between lens fiber cells.
The second extracellular loop domain (E2) is primarily responsible for this
adhesive function. Treatment with a fusion protein containing E2 domain inhibited
cell adhesion. Furthermore, disruption of cell adhesion by the E2 domains
impaired primary lens cell differentiation. Five critical amino acid residues in
the E2 domain primarily are involved in cell adhesive function as well as lens
epithelial-fiber differentiation. Together, these results suggest that in
addition to forming gap junction channels, Cx50 acts as an adhesive molecule that
is critical in maintaining lens fiber integrity and epithelial-fiber
differentiation.
PMID- 28706246
TI - Combined Impact of Known Lifestyle Factors on Total and Cause-Specific Mortality
among Chinese Men: A Prospective Cohort Study.
AB - Impact of combined lifestyles on risk of mortality needs to be explored
quantitatively. We aimed to evaluate the associations of combined lifestyle
factors with total and cause-specific mortality in Chinese men. We used data from
the Shanghai Men's Health Study (2002-2013), an on-going population-based
prospective cohort study of men (aged 40 to 74 years). Four traditional
unfavorable lifestyle factors were included: smoking, heavy alcohol use,
unhealthy diet and physical inactivity. Cox proportional hazards models were used
to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs). Among
about 61,480 men in the cohort, a total of 4,952 men died, of which 1,637 men
died from cardiovascular diseases (CVD), 2,122 from cancer during a median of
9.29 years' follow-up. The HRs of men with four risk practices comparing to those
with zero were 2.92 (95%CI: 2.53, 3.38) for all-cause mortality, 3.15 (95%CI:
2.44, 4.05) for CVD mortality, and 3.18 (95%CI: 2.55, 3.97) for cancer mortality.
The population attributable risks (PARs) were 0.41, 0.40 and 0.38 for total, CVD
and cancer mortality, accordingly. As combined unhealthy lifestyle behaviors had
substantial impact on total and cause-specific mortality, promotion of healthy
lifestyle should be a public health priority.
PMID- 28706247
TI - The unprecedented 2015/16 Tasman Sea marine heatwave.
AB - The Tasman Sea off southeast Australia exhibited its longest and most intense
marine heatwave ever recorded in 2015/16. Here we report on several inter-related
aspects of this event: observed characteristics, physical drivers, ecological
impacts and the role of climate change. This marine heatwave lasted for 251 days
reaching a maximum intensity of 2.9 degrees C above climatology. The anomalous
warming is dominated by anomalous convergence of heat linked to the southward
flowing East Australian Current. Ecosystem impacts range from new disease
outbreaks in farmed shellfish, mortality of wild molluscs and out-of-range
species observations. Global climate models indicate it is very likely to be that
the occurrence of an extreme warming event of this duration or intensity in this
region is respectively >=330 times and >=6.8 times as likely to be due to the
influence of anthropogenic climate change. Climate projections indicate that
event likelihoods will increase in the future, due to increasing anthropogenic
influences.
PMID- 28706248
TI - Acoustic-transfection for genomic manipulation of single-cells using high
frequency ultrasound.
AB - Efficient intracellular delivery of biologically active macromolecules has been a
challenging but important process for manipulating live cells for research and
therapeutic purposes. There have been limited transfection techniques that can
deliver multiple types of active molecules simultaneously into single-cells as
well as different types of molecules into physically connected individual
neighboring cells separately with high precision and low cytotoxicity. Here, a
high frequency ultrasound-based remote intracellular delivery technique capable
of delivery of multiple DNA plasmids, messenger RNAs, and recombinant proteins is
developed to allow high spatiotemporal visualization and analysis of gene and
protein expressions as well as single-cell gene editing using clustered regularly
interspaced short palindromic repeats (CRISPR)-associated protein-9 nuclease
(Cas9), a method called acoustic-transfection. Acoustic-transfection has
advantages over typical sonoporation because acoustic-transfection utilizing
ultra-high frequency ultrasound over 150 MHz can directly deliver gene and
proteins into cytoplasm without microbubbles, which enables controlled and local
intracellular delivery to acoustic-transfection technique. Acoustic-transfection
was further demonstrated to deliver CRISPR-Cas9 systems to successfully modify
and reprogram the genome of single live cells, providing the evidence of the
acoustic-transfection technique for precise genome editing using CRISPR-Cas9.
PMID- 28706249
TI - Offspring sex and parental health and mortality.
AB - Increased mortality has been observed in mothers and fathers with male offspring
but little is known regarding specific diseases. In a register linkage we linked
women born 1925-1954 having survived to age 50 (n = 661,031) to offspring and
fathers (n = 691,124). Three approaches were used: 1) number of total boy and
girl offspring, 2) sex of the first and second offspring and 3) proportion of
boys to total number of offspring. A sub-cohort (n = 50,736 mothers, n = 44,794
fathers) from survey data was analysed for risk factors. Mothers had increased
risk of total and cardiovascular mortality that was consistent across approaches:
cardiovascular mortality of 1.07 (95% CI: 1.03-1.11) per boy (approach 2), 1.04
(1.01-1.07) if the first offspring was a boy, and 1.06 (1.01-1.10) if the first
two offspring were boys (approach 3). We found that sex of offspring was not
associated with total or cardiovascular mortality in fathers. For other diseases
or risk factors no robust associations were seen in mothers or fathers. Increased
cardiovascular risk in mothers having male offspring suggests a maternal disease
specific mechanism. The lack of consistent associations on measured risk factors
could suggest other biological pathways than those studied play a role in
generating this additional cardiovascular risk.
PMID- 28706250
TI - Metal-organic-frameworks derived cobalt embedded in various carbon structures as
bifunctional electrocatalysts for oxygen reduction and evolution reactions.
AB - A series of nanocomposites of cobalt embedded in N-doped nanoporous carbons,
carbon nanotubes or hollow carbon onions have been synthesized by a one-step
carbonization of metal-organic-framework ZIF-67. The effect of the carbonization
temperature on the structural evolution of the resulting nanocomposites has been
investigated in detail. Among the as-synthesized materials, the cobalt/nanoporous
N-doped carbon composites have demonstrated excellent electrocatalytic activities
and durability towards oxygen reduction reaction in alkaline medium. Compared to
the benchmark Pt/C catalyst, the optimized Co@C-800 (carbonized at 800 degrees
C) exhibited high oxygen reduction reaction activity with an onset potential of
0.92 V, and a half-wave potential of 0.82 V. Moreover, the optimized Co@C-800
also showed enhanced electrocatalytic activity towards oxygen evolution reaction
from water splitting, with a low onset potential of 1.43 V and a potential of
1.61 V at 10 mA cm-2 current density. This work offered a simple solution to
develop metal-organic-framework-derived materials for highly efficient
electrochemical applications.
PMID- 28706251
TI - Frequency conversion in ultrastrong cavity QED.
AB - We propose a new method for frequency conversion of photons which is both
versatile and deterministic. We show that a system with two resonators
ultrastrongly coupled to a single qubit can be used to realise both single- and
multiphoton frequency-conversion processes. The conversion can be exquisitely
controlled by tuning the qubit frequency to bring the desired frequency
conversion transitions on or off resonance. Considering recent experimental
advances in ultrastrong coupling for circuit QED and other systems, we believe
that our scheme can be implemented using available technology.
PMID- 28706252
TI - Corrigendum: Recent pause in the growth rate of atmospheric CO2 due to enhanced
terrestrial carbon uptake.
AB - This corrects the article DOI: 10.1038/ncomms13428.
PMID- 28706253
TI - Affinity purification of erythropoietin from cell culture supernatant combined
with MALDI-TOF-MS analysis of erythropoietin N-glycosylation.
AB - Erythropoietin (EPO) is a heavily glycosylated hormone whose recombinant forms
are used for treatment of anaemia. EPO glycosylation is important for its
pharmacological properties. An analytical workflow, which can determine EPO
glycosylation in an accurate and high-throughput fashion from cell culture
supernatant (CCS) in approximately 24 h, offers the possibility to follow changes
during production. To address this challenge, we present a complete workflow
consisting of protein purification, glycan release, sialic acid derivatization,
solid phase extraction, matrix-assisted laser desorption/ionization - mass
spectrometry (MALDI-MS) analysis and MassyTools data processing. EPO purification
from CCS by anti-EPO antibody coupled Sepharose beads yielded excellent purity
with acceptable recovery and was free of glycoform bias. Glycosylation profiles
obtained by MALDI-MS were highly comparable to those obtained with an established
capillary gel electrophoresis-laser induced fluorescence method. Our method
delivers accurate results for the analysis of changes of important glycosylation
parameters, such as sialylation and number of N-acetyllactosamine units, for the
time course of a fermentation. We could resolve differences in glycosylation
between several CCS samples.
PMID- 28706254
TI - MiR-30a targets IL-1alpha and regulates islet functions as an inflammation buffer
and response factor.
AB - Diabetes is an inflammatory disease. Inflammation plays an important role in
islet functions. However, the exact mechanisms by which inflammation affects
islet functions remain unclear. In this study, we investigated the regulatory
effects of miR-30a on inflammation and islet functions. The results indicate that
miR-30a serves as an inflammation-resolving buffer factor by targeting
interleukin 1a (IL-1alpha) in immune cells and in islet cells, which might play
an important role in inflammation homeostasis. miR-30a ameliorates islet
functions in an inflammatory micro-environment by targeting the IL-1alpha/nuclear
factor kappa B (NFKB) p65 subunit (p65)/p62 (SQSTM1)/insulin axis, which can be
developed into a novel antidiabetic approach. miR-30a serves as a promising
inflammation-response biomarker in inflammatory diseases and is possibly
activated by the toll-like receptor 4 (TLR4)/IL-1alpha/NFKB pathways. However,
the exact molecular mechanisms by which miR-30a regulates inflammation and islet
functions as well as the potential applications in transitional medicine require
further elucidation.
PMID- 28706255
TI - Mitsugumin 29 regulates t-tubule architecture in the failing heart.
AB - Transverse tubules (t-tubules) are uniquely-adapted membrane invaginations in
cardiac myocytes that facilitate the synchronous release of Ca2+ from internal
stores and subsequent myofilament contraction, although these structures become
disorganized and rarefied in heart failure. We previously observed that
mitsugumin 29 (Mg29), an important t-tubule organizing protein in skeletal
muscle, was induced in the mouse heart for the first time during dilated
cardiomyopathy with heart failure. Here we generated cardiac-specific transgenic
mice expressing Mg29 to model this observed induction in the failing heart.
Interestingly, expression of Mg29 in the hearts of Csrp3 null mice (encoding
muscle LIM protein, MLP) partially restored t-tubule structure and preserved
cardiac function as measured by invasive hemodynamics, without altering Ca2+
spark frequency. Conversely, gene-deleted mice lacking both Mg29 and MLP protein
showed a further reduction in t-tubule organization and accelerated heart
failure. Thus, induction of Mg29 in the failing heart is a compensatory response
that directly counteracts the well-characterized loss of t-tubule complexity and
reduced expression of anchoring proteins such as junctophilin-2 (Jph2) that
normally occur in this disease. Moreover, preservation of t-tubule structure by
Mg29 induction significantly increases the function of the failing heart.
PMID- 28706256
TI - An extremely high dietary iodide supply forestalls severe hypothyroidism in Na+/I
symporter (NIS) knockout mice.
AB - The sodium/iodide symporter (NIS) mediates active iodide (I-) accumulation in the
thyroid, the first step in thyroid hormone (TH) biosynthesis. Mutations in the
SLC5A5 gene encoding NIS that result in a non-functional protein lead to
congenital hypothyroidism due to I- transport defect (ITD). ITD is a rare
autosomal disorder that, if not treated promptly in infancy, can cause mental
retardation, as the TH decrease results in improper development of the nervous
system. However, in some patients, hypothyroidism has been ameliorated by
unusually large amounts of dietary I-. Here we report the first NIS knockout (KO)
mouse model, obtained by targeting exons 6 and 7 of the Slc5a5 gene. In NIS KO
mice, in the thyroid, stomach, and salivary gland, NIS is absent, and hence there
is no active accumulation of the NIS substrate pertechnetate (99mTcO4-). NIS KO
mice showed undetectable serum T4 and very low serum T3 levels when fed a diet
supplying the minimum I- requirement for rodents. These hypothyroid mice
displayed oxidative stress in the thyroid, but not in the brown adipose tissue or
liver. Feeding the mice a high-I- diet partially rescued TH biosynthesis,
demonstrating that, at high I- concentrations, I- enters the thyroid through
routes other than NIS.
PMID- 28706257
TI - Efficacy and safety of taxane-based systemic chemotherapy of advanced gastric
cancer: A systematic review and meta-analysis.
AB - Taxanes are chemotherapeutic agents commonly used to treat several cancers.
However, the effects of taxanes on advanced gastric cancer (AGC) are still not
clear, especially when used as a first-line treatment. This systematic review and
meta-analysis aims to investigate the efficacy and safety of taxanes as a first
line treatment of AGC. The quality of our included studies was assessed using the
Cochrane risk of bias tool for RCTs and NOS scale for nRCTs, and the data of the
included studies was of satisfactory quality to analyze. The outcomes included
overall survival (OS), progression-free survival (PFS), overall response rate
(ORR), and toxicity. Taxanes significantly improved OS (HR = 0.84, 95% CI 0.76
0.92, P = 0.0004) and had a slight effect on ORR (RR = 1.23, 95% CI 1.00-1.51, P
= 0.05). However, taxanes may also increase the risks of neutropenia and
leucopenia, similar to effects observed in other conventional chemotherapeutic
treatments such as oxaliplatin and epirubicin. Therefore, patient characteristics
including concomitant diseases, physical condition, and prior therapies should be
considered before selecting taxane-based treatments for AGC.
PMID- 28706258
TI - Transverse Coherence Limited Coherent Diffraction Imaging using a Molybdenum Soft
X-ray Laser Pumped at Moderate Pump Energies.
AB - Coherent diffraction imaging (CDI) in the extreme ultraviolet has become an
important tool for nanoscale investigations. Laser-driven high harmonic
generation (HHG) sources allow for lab scale applications such as cancer cell
classification and phase-resolved surface studies. HHG sources exhibit excellent
coherence but limited photon flux due poor conversion efficiency. In contrast,
table-top soft X-ray lasers (SXRL) feature excellent temporal coherence and
extraordinary high flux at limited transverse coherence. Here, the performance of
a SXRL pumped at moderate pump energies is evaluated for CDI and compared to a
HHG source. For CDI, a lower bound for the required mutual coherence factor of
|MU 12| >= 0.75 is found by comparing a reconstruction with fixed support to a
conventional characterization using double slits. A comparison of the captured
diffraction signals suggests that SXRLs have the potential for imaging micron
scale objects with sub-20 nm resolution in orders of magnitude shorter
integration time compared to a conventional HHG source. Here, the low transverse
coherence diameter limits the resolution to approximately 180 nm. The
extraordinary high photon flux per laser shot, scalability towards higher
repetition rate and capability of seeding with a high harmonic source opens a
route for higher performance nanoscale imaging systems based on SXRLs.
PMID- 28706259
TI - Genetic polymorphisms of C-type lectin receptors in Behcet's disease in a Chinese
Han population.
AB - C-type lectin receptors (CLRs) have been demonstrated to be involved in several
autoimmune diseases. The role of CLRs in Behcet's disease (BD) is unknown and
thus was the purpose of this study. A two-stage association study was carried out
and a total of 766 BD patients and 1674 healthy controls were recruited.
Genotyping of 14 SNPs of 13 genes in CLRs was carried out by iPLEX Gold
genotyping or polymerase chain reaction-restriction fragment length polymorphism
(PCR-RFLP) assay. The expression of mannose binding lectin 2 (MBL2) and killer
cell lectin like receptor C4 (KLRC4) was measured by Real-time PCR. Significantly
increased frequencies of the A allele as well as AA genotype of rs1800450 in MBL2
(Pc = 2.50 * 10-6, OR = 1.494; Pc = 2.24 * 10-6,OR = 2.899; respectively) and TT
genotype of rs2617170 in KLRC4 (Pc = 2.53 * 10-6, OR = 1.695) and decreased
frequencies of GG genotype of rs1800450 (Pc = 1.56 * 10-3, OR = 0.689) and C
allele as well as CC genotype of rs2617170 (Pc = 2.05 * 10-9,OR = 0.664; Pc =
1.20 * 10-5, OR = 0.585; respectively) were observed in BD. Two variants,
p.Gly54Asp (rs1800450) and p.Asn104Ser (rs2617170) affect MBL2 and KLRC4 protein
stability and expression. Our study demonstrates that the MBL2/rs1800450 and
KLRC4/rs2617170 are susceptibility factors for BD in a Chinese Han population.
PMID- 28706260
TI - Early intervention with Bifidobacterium lactis NCC2818 modulates the host-microbe
interface independent of the sustained changes induced by the neonatal
environment.
AB - Inflammatory and metabolic diseases can originate during early-life and have been
correlated with shifts in intestinal microbial ecology. Here we demonstrate that
minor environmental fluctuations during the early neonatal period had sustained
effects on the developing porcine microbiota and host-microbe interface. These
inter-replicate effects appear to originate during the first day of life, and are
likely to reflect very early microbiota acquisition from the environment. We
statistically link early systemic inflammation with later local increases in
inflammatory cytokine (IL-17) production, which could have important enteric
health implications. Immunity, intestinal barrier function, host metabolism and
host-microbiota co-metabolism were further modified by Bifidobacterium lactis
NCC2818 supplementation, although composition of the in situ microbiota remained
unchanged. Finally, our robust model identified novel, strong correlations
between urinary metabolites (eg malonate, phenylacetylglycine, alanine) and
mucosal immunoglobulin (IgM) and cytokine (IL-10, IL-4) production, thus
providing the possibility of the development of urinary 'dipstick' tests to
assess non-accessible mucosal immune development and identify early precursors
(biomarkers) of disease. These results have important implications for infants
exposed to neonatal factors including caesarean delivery, antibiotic therapy and
delayed discharge from hospital environments, which may predispose to the
development of inflammatory and metabolic diseases in later life.
PMID- 28706261
TI - PLAG1 deficiency impairs spermatogenesis and sperm motility in mice.
AB - Deficiency in pleomorphic adenoma gene 1 (PLAG1) leads to reduced fertility in
male mice, but the mechanism by which PLAG1 contributes to reproduction is
unknown. To investigate the involvement of PLAG1 in testicular function, we
determined (i) the spatial distribution of PLAG1 in the testis using X-gal
staining; (ii) transcriptomic consequences of PLAG1 deficiency in knock-out and
heterozygous mice compared to wild-type mice using RNA-seq; and (iii)
morphological and functional consequences of PLAG1 deficiency by determining
testicular histology, daily sperm production and sperm motility in knock-out and
wild-type mice. PLAG1 was sparsely expressed in germ cells and in Sertoli cells.
Genes known to be involved in spermatogenesis were downregulated in the testes of
knock-out mice, as well as Hsd17b3, which encodes a key enzyme in androgen
biosynthesis. In the absence of Plag1, a number of genes involved in immune
processes and epididymis-specific genes were upregulated in the testes. Finally,
loss of PLAG1 resulted in significantly lowered daily sperm production, in
reduced sperm motility, and in several animals, in sloughing of the germinal
epithelium. Our results demonstrate that the subfertility seen in male PLAG1
deficient mice is, at least in part, the result of significantly reduced sperm
output and sperm motility.
PMID- 28706262
TI - Impairment of Neuroplasticity in the Dorsolateral Prefrontal Cortex by Alcohol.
AB - Previous studies have demonstrated that alcohol consumption impairs
neuroplasticity in the motor cortex. However, it is unknown whether alcohol
produces a similar impairment of neuroplasticity in the dorsolateral prefrontal
cortex (DLPFC), a brain region that plays an important role in cognitive
functioning. The aim of the current study was to evaluate the effect of alcohol
intoxication on neuroplasticity in the DLPFC. Paired associative stimulation
(PAS) combined with electroencephalography (EEG) was used for the induction and
measurement of associative LTP-like neuroplasticity in the DLPFC. Fifteen healthy
subjects were administered PAS to the DLPFC following consumption of an alcohol
(1.5 g/l of body water) or placebo beverage in a within-subject cross-over
design. PAS induced neuroplasticity was indexed up to 60 minutes following PAS.
Additionally, the effect of alcohol on PAS-induced potentiation of theta-gamma
coupling (an index associated with learning and memory) was examined prior to and
following PAS. Alcohol consumption resulted in a significant impairment of mean
(t = 2.456, df = 13, p = 0.029) and maximum potentiation (t = -2.945, df = 13, p
= 0.011) compared to the placebo beverage in the DLPFC and globally. Alcohol also
suppressed the potentiation of theta-gamma coupling by PAS. Findings from the
present study provide a potential neurophysiological mechanism for impairment of
cognitive functioning by alcohol.
PMID- 28706263
TI - The influence of electrical effects on device performance of organic solar cells
with nano-structured electrodes.
AB - Integration of light-trapping features and exploitation of metal nanostructure
plasmonic effects are promising approaches for enhancing the power conversion
efficiency of organic solar cells. These approaches' effects on the light
absorption enhancement have been widely studied, especially in inorganic devices.
While this light-trapping concept can be transferred to organic devices, one has
to also consider nanostructure-induced electrical effects on the device
performance, due to the fundamental difference in the organic semiconducting
material properties compared to their inorganic counterparts. In this
contribution, we exemplarily model the electrical properties of organic solar
cells with rectangular-grating structures, as compared to planar reference
devices. Based on our numeric results, we demonstrate that, beyond an optical
absorption enhancement, the device fill factor improves significantly by
introducing the grating structures. From the simulations we conclude that
enhanced carrier collection efficiency is the main reason for the increased solar
cell fill factor. This work contributes towards a more fundamental understanding
of the effect of nanostructured electrodes on the electrical properties of
organic solar cells.
PMID- 28706264
TI - First-Principles Study of Sodium Intercalation in Crystalline Na x Si24 (0 <= x
<= 4) as Anode Material for Na-ion Batteries.
AB - The search for Si-based anodes capable of undergoing low volume changes during
electrochemical operation in rechargeable batteries is ample and active. Here we
focus on crystalline Si24, a recently discovered open-cage allotrope of silicon,
to thoroughly investigate its electrochemical performance using density
functional theory calculations. In particular, we examine the phase stability of
Na x Si24 along the whole composition range (0 <= x <= 4), volume and voltage
changes during the (de)sodiation process, and sodium ion mobility. We show that
Na x Si24 forms a solid solution with minimal volume changes. Yet sodium
diffusion is predicted to be insufficiently fast for facile kinetics of Na-ion
intake. Considering these advantages and limitations, we discuss the potential
usefulness of Si24 as anode material for Na-ion batteries.
PMID- 28706265
TI - Epigenetics: Therapy-induced transcription is cryptically widespread.
PMID- 28706267
TI - A Simple Add-and-Display Method for Immobilisation of Cancer Drug on His-tagged
Virus-like Nanoparticles for Controlled Drug Delivery.
AB - pH-responsive virus-like nanoparticles (VLNPs) hold promising potential as drug
delivery systems for cancer therapy. In the present study, hepatitis B virus
(HBV) VLNPs harbouring His-tags were used to display doxorubicin (DOX) via
nitrilotriacetic acid (NTA) conjugation. The His-tags served as pH-responsive
nanojoints which released DOX from VLNPs in a controlled manner. The His-tagged
VLNPs conjugated non-covalently with NTA-DOX, and cross-linked with folic acid
(FA) were able to specifically target and deliver the DOX into ovarian cancer
cells via folate receptor (FR)-mediated endocytosis. The cytotoxicity and
cellular uptake results revealed that the His-tagged VLNPs significantly
increased the accumulation of DOX in the ovarian cancer cells and enhanced the
uptake of DOX, which improved anti-tumour effects. This study demonstrated that
NTA-DOX can be easily displayed on His-tagged VLNPs by a simple Add-and-Display
step with high coupling efficiency and the drug was only released at low pH in a
controlled manner. This approach facilitates specific attachment of any drug
molecule on His-tagged VLNPs at the very mild conditions without changing the
biological structure and native conformation of the VLNPs.
PMID- 28706268
TI - Effect of water activity on rates of serpentinization of olivine.
AB - The hydrothermal alteration of mantle rocks (referred to as serpentinization)
occurs in submarine environments extending from mid-ocean ridges to subduction
zones. Serpentinization affects the physical and chemical properties of oceanic
lithosphere, represents one of the major mechanisms driving mass exchange between
the mantle and the Earth's surface, and is central to current origin of life
hypotheses as well as the search for microbial life on the icy moons of Jupiter
and Saturn. In spite of increasing interest in the serpentinization process by
researchers in diverse fields, the rates of serpentinization and the controlling
factors are poorly understood. Here we use a novel in situ experimental method
involving olivine micro-reactors and show that the rate of serpentinization is
strongly controlled by the salinity (water activity) of the reacting fluid and
demonstrate that the rate of serpentinization of olivine slows down as salinity
increases and H2O activity decreases.
PMID- 28706266
TI - Microenvironmental regulation of tumour angiogenesis.
AB - Tumours display considerable variation in the patterning and properties of
angiogenic blood vessels, as well as in their responses to anti-angiogenic
therapy. Angiogenic programming of neoplastic tissue is a multidimensional
process regulated by cancer cells in concert with a variety of tumour-associated
stromal cells and their bioactive products, which encompass cytokines and growth
factors, the extracellular matrix and secreted microvesicles. In this Review, we
discuss the extrinsic regulation of angiogenesis by the tumour microenvironment,
highlighting potential vulnerabilities that could be targeted to improve the
applicability and reach of anti-angiogenic cancer therapies.
PMID- 28706269
TI - Insulin resistance and obesity among infertile women with different polycystic
ovary syndrome phenotypes.
AB - Polycystic ovary syndrome (PCOS) is a common problem among Arab women and is the
main cause of infertility due to anovulation. This study investigates insulin
resistance (IR) and obesity in different PCOS phenotypes among infertile women (n
= 213), of whom 159 had PCOS and 54 women without PCOS, recruited as a control
group. Biometric, hormonal and clinical parameters were studied. IR was observed
in 133 (83.6%) women with PCOS and in 25 (46.3%) women without PCOS (p < 0.001).
IR was significantly associated with PCOS only among women with central obesity
(chi2 = 35.0, p < 0.001) and not for the normal category (chi2 = 4.04, p <
0.058). The LH/FSH ratio was not significantly different among the PCOS group (n
= 37, 23.3%) compared to the control group (n = 9, 16.7%) (p = 0.308). Among
women with PCOS, the most common phenotype was type I (50.3%), with type III
(29.6%), type II (14.5%) and type IV (5.7%). Type I had the highest values of
fasting insulin (median = 12.98 mU/mL) and HOMA IR values (significant difference
among the four phenotypes, p = 0.009 and 0.006, respectively) and is associated
with severity of the disease. There was no difference in glucose levels.
PMID- 28706270
TI - Comprehensive Multi-Dimensional MRI for the Simultaneous Assessment of
Cardiopulmonary Anatomy and Physiology.
AB - Diagnostic testing often assesses the cardiovascular or respiratory systems in
isolation, ignoring the major pathophysiologic interactions between the systems
in many diseases. When both systems are assessed currently, multiple modalities
are utilized in costly fashion with burdensome logistics and decreased
accessibility. Thus, we have developed a new acquisition and reconstruction
paradigm using the flexibility of MRI to enable a comprehensive exam from a
single 5-15 min scan. We constructed a compressive-sensing approach to pseudo
randomly acquire highly subsampled, multi-dimensionally-encoded and time-stamped
data from which we reconstruct volumetric cardiac and respiratory motion phases,
contrast-agent dynamics, and blood flow velocity fields. The proposed method,
named XD flow, is demonstrated for (a) evaluating congenital heart disease, where
the impact of bulk motion is reduced in a non-sedated neonatal patient and (b)
where the observation of the impact of respiration on flow is necessary for
diagnostics; (c) cardiopulmonary imaging, where cardiovascular flow, function,
and anatomy information is needed along with pulmonary perfusion quantification;
and in (d) renal function imaging, where blood velocities and glomerular
filtration rates are simultaneously measured, which highlights the generality of
the technique. XD flow has the ability to improve quantification and to provide
additional data for patient diagnosis for comprehensive evaluations.
PMID- 28706271
TI - Joint Covariate Detection on Expression Profiles for Identifying MicroRNAs
Related to Venous Metastasis in Hepatocellular Carcinoma.
AB - Expression profiles of cancer are generally composed of three dimensions
including gene probes, patients (e.g., metastasis or non-metastasis) and tissues
(i.e., cancer or normal cells of a patient). In order to combine these three
dimensions, we proposed a joint covariate detection that not only considered
projections on gene probes and tissues simultaneously, but also concentrated on
distinguishing patients into different groups. Due to highly lethal malignancy of
hepatocellular carcinoma, we chose data GSE6857 to testify the effectiveness of
our method. A bootstrap and accumulation strategy was introduced in, which could
select candidate microRNAs to distinguish metastasis from non-metastasis patient
group. Two pairs of microRNAs were further selected. Each component of either
significant microRNA pair was derived from different cliques. Targets were sought
and pathway analysis were made, which might reveal the mechanism of venous
metastasis in primary hepatocellular carcinoma.
PMID- 28706272
TI - Modeling Atrial Fibrillation using Human Embryonic Stem Cell-Derived Atrial
Tissue.
AB - Since current experimental models of Atrial Fibrillation (AF) have significant
limitations, we used human embryonic stem cells (hESCs) to generate an atrial
specific tissue model of AF for pharmacologic testing. We generated atrial-like
cardiomyocytes (CMs) from hESCs which preferentially expressed atrial-specific
genes, and had shorter action potential (AP) durations compared to ventricular
like CMs. We then generated confluent atrial-like CM sheets and interrogated them
using optical mapping techniques. Atrial-like CM sheets (~1 cm in diameter)
showed uniform AP propagation, and rapid re-entrant rotor patterns, as seen in AF
could be induced. Anti-arrhythmic drugs were tested on single atrial-like CMs and
cell sheets. Flecainide profoundly slowed upstroke velocity without affecting AP
duration, leading to reduced conduction velocities (CVs), curvatures and cycle
lengths of rotors, consistent with increased rotor organization and expansion. By
contrast, consistent with block of rapid delayed rectifier K+ currents (Ikr) and
AP prolongation in isolated atrial-like CMs, dofetilide prolonged APs and reduced
cycle lengths of rotors in cell sheets without affecting CV. In conclusion, using
our hESC-derived atrial CM preparations, we demonstrate that flecainide and
dofetilide modulate reentrant arrhythmogenic rotor activation patterns in a
manner that helps explain their efficacy in treating and preventing AF.
PMID- 28706273
TI - Marangoni effect induced macro porous surface films prepared through a facile sol
gel route.
AB - Based on TiO2 as a model system, the sol-gel one step facile method is
established to fabricate the macro-porous morphology films on the basis of
Marangoni effect. In this proposed mechanism, the binary mixture of hydrophilic
CuCl2 and lipophilic Ti-O network is used in sol to produce phase separation. A
suitable evaporation rate in the gel film process leads to the macro-porous film
due to Marangoni effect. It is observed that the macro-porous morphology of the
film sustains during the annealing process, which suggests the creation of porous
surface morphology in gel film stage rather than due to annealing. To analyze the
preparation mechanism, the sol-gel process and microstructure of films are
examined using TG-DTA, SEM, TEM, XRD, Raman, UV-Vis, XPS and FTIR. Furthermore,
the optical-thermal properties are studied for the potential applications of such
porous surface films as solar selective absorber.
PMID- 28706274
TI - Elovanoids are novel cell-specific lipid mediators necessary for neuroprotective
signaling for photoreceptor cell integrity.
AB - Docosahexaenoic acid (DHA, 22:6 n-3) is abundant in the retina and is
enzymatically converted into pro-homeostatic docosanoids. The DHA- or
eicosapentaenoic acid (EPA)-derived 26 carbon fatty acid is a substrate of
elongase ELOVL4, which is expressed in photoreceptor cells and generates very
long chain (>=C28) polyunsaturated fatty acids including n-3 (VLC-PUFAs,n-3).
While ELOVL4 mutations are linked to vision loss and neuronal dysfunctions, the
roles of VLC-PUFAs remain unknown. Here we report a novel class of lipid
mediators biosynthesized in human retinal pigment epithelial (RPE) cells that are
oxygenated derivatives of VLC-PUFAs,n-3; we termed these mediators elovanoids
(ELV). ELVs have structures reminiscent of docosanoids but with different
physicochemical properties and alternatively-regulated biosynthetic pathways. The
structures, stereochemistry, and bioactivity of ELVs were determined using
synthetic materials produced by stereo-controlled chemical synthesis. ELVs
enhance expression of pro-survival proteins in cells undergoing uncompensated
oxidative stress. Our findings unveil a novel autocrine/paracrine pro-homeostatic
RPE cell signaling that aims to sustain photoreceptor cell integrity and reveal
potential therapeutic targets for retinal degenerations.
PMID- 28706275
TI - Novel function of pregnancy-associated plasma protein A: promotes endometrium
receptivity by up-regulating N-fucosylation.
AB - Glycosylation of uterine endometrial cells plays important roles to determine
their receptive function to blastocysts. Trophoblast-derived pregnancy-associated
plasma protein A (PAPPA) is specifically elevated in pregnant women serum, and is
known to promote trophoblast cell proliferation and adhesion. However, the
relationship between PAPPA and endometrium receptivity, as well as the regulation
of N-fucosylation remains unclear. We found that rhPAPPA and PAPPA in the serum
samples from pregnant women or conditioned medium of trophoblast cells promoted
endometrium receptivity in vitro. Moreover, rhPAPPA increased alpha1,2-, alpha1,3
and alpha1,6-fucosylation levels by up-regulating N-fucosyltransferases FUT1,
FUT4 and FUT8 expression, respectively, through IGF-1R/PI3K/Akt signaling pathway
in human endometrial cells. Additionally, alpha1,2-, alpha1,3- and alpha1,6
fucosylation of integrin alphaVbeta3, a critical endometrium receptivity
biomarker, was up-regulated by PAPPA, thereby enhanced its adhesive functions.
Furthermore, PAPPA blockage with antibody inhibited embryo implantation in vivo,
mouse embryo adhesion and spreading in vitro, as well as N-fucosylation level of
the endometrium in pregnant mice. In summary, this study suggests that PAPPA is
essential to maintain a receptive endometrium by up-regulating N-fucosylation,
which is a potential useful biomarker to evaluate the receptive functions of the
endometrium.
PMID- 28706276
TI - Kanyawara Virus: A Novel Rhabdovirus Infecting Newly Discovered Nycteribiid Bat
Flies Infesting Previously Unknown Pteropodid Bats in Uganda.
AB - Bats are natural reservoir hosts of highly virulent pathogens such as Marburg
virus, Nipah virus, and SARS coronavirus. However, little is known about the role
of bat ectoparasites in transmitting and maintaining such viruses. The intricate
relationship between bats and their ectoparasites suggests that ectoparasites
might serve as viral vectors, but evidence to date is scant. Bat flies, in
particular, are highly specialized obligate hematophagous ectoparasites that
incidentally bite humans. Using next-generation sequencing, we discovered a novel
ledantevirus (mononegaviral family Rhabdoviridae, genus Ledantevirus) in
nycteribiid bat flies infesting pteropodid bats in western Uganda. Mitochondrial
DNA analyses revealed that both the bat flies and their bat hosts belong to
putative new species. The coding-complete genome of the new virus, named
Kanyawara virus (KYAV), is only distantly related to that of its closest known
relative, Mount Elgon bat virus, and was found at high titers in bat flies but
not in blood or on mucosal surfaces of host bats. Viral genome analysis indicates
unusually low CpG dinucleotide depletion in KYAV compared to other ledanteviruses
and rhabdovirus groups, with KYAV displaying values similar to rhabdoviruses of
arthropods. Our findings highlight the possibility of a yet-to-be-discovered
diversity of potentially pathogenic viruses in bat ectoparasites.
PMID- 28706278
TI - Enhanced photoelectrochemical properties of nanocrystalline TiO2 electrode by
surface sensitization with CuxO quantum dots.
AB - Nanoporous anatase TiO2 films were fabricated by a screen-printing method, and
CuxO quantum dots (QDs) were deposited on the TiO2 films through successive ionic
layer adsorption and reaction (SILAR). The amount of CuxO QDs on the TiO2 films
are controlled by changing the number of SILAR cycles. The morphology,
microstructure, optical, and photoelectrochemical properties of different CuxO
sensitized TiO2 films (CuxO/TiO2) were investigated in detail. The nanoporous
TiO2 film offers a large surface area for anchoring QDs. QD deposited samples
exhibited a significant improvement in photoelectrochemical performance than the
bare of TiO2. CuxO/TiO2, prepared with 7 SILAR cycles, showed the best
photoelectrochemical properties, where the photocurrent density was enhanced to
500.01 MUA/cm2 compared with 168.88 MUA/cm2 of bare TiO2 under visible light.
These results indicate that the designed CuxO/TiO2 structure possesses superior
charge separation efficiency and photoelectrochemical properties.
PMID- 28706277
TI - DNA binding drives the association of BRG1/hBRM bromodomains with nucleosomes.
AB - BRG1 and BRM, central components of the BAF (mSWI/SNF) chromatin remodelling
complex, are critical in chromatin structure regulation. Here, we show that the
human BRM (hBRM) bromodomain (BRD) has moderate specificity for H3K14ac.
Surprisingly, we also find that both BRG1 and hBRM BRDs have DNA-binding
activity. We demonstrate that the BRDs associate with DNA through a surface basic
patch and that the BRD and an adjacent AT-hook make multivalent contacts with
DNA, leading to robust affinity and moderate specificity for AT-rich elements.
Although we show that the BRDs can bind to both DNA and H3K14ac simultaneously,
the histone-binding activity does not contribute substantially to nucleosome
targeting in vitro. In addition, we find that neither BRD histone nor DNA binding
contribute to the global chromatin affinity of BRG1 in mouse embryonic stem
cells. Together, our results suggest that association of the BRG1/hBRM BRD with
nucleosomes plays a regulatory rather than targeting role in BAF activity.
PMID- 28706279
TI - Elimination of undifferentiated human embryonic stem cells by cardiac glycosides.
AB - An important safety concern in the use of human pluripotent stem cells (hPSCs) is
tumorigenic risk, because these cells can form teratomas after an in vivo
injection at ectopic sites. Several thousands of undifferentiated hPSCs are
sufficient to induce teratomas in a mouse model. Thus, it is critical to remove
all residue-undifferentiated hPSCs that have teratoma potential before the
clinical application of hPSC-derived cells. In this study, our data demonstrated
the cytotoxic effects of cardiac glycosides, such as digoxin, lanatoside C,
bufalin, and proscillaridin A, in human embryonic stem cells (hESCs). This
phenomenon was not observed in human bone marrow mesenchymal stem cells
(hBMMSCs). Most importantly, digoxin and lanatoside C did not affect the stem
cells' differentiation ability. Consistently, the viability of the hESC-derived
MSCs, neurons, and endothelium cells was not affected by the digoxin and
lanatoside C treatment. Furthermore, the in vivo experiments demonstrated that
digoxin and lanatoside C prevented teratoma formation. To the best of our
knowledge, this study is the first to describe the cytotoxicity and tumor
prevention effects of cardiac glycosides in hESCs. Digoxin and lanatoside C are
also the first FDA-approved drugs that demonstrated cytotoxicity in
undifferentiated hESCs.
PMID- 28706280
TI - Radiation-induced changes in the glycome of endothelial cells with functional
consequences.
AB - As it is altered by ionizing radiation, the vascular network is considered as a
prime target in limiting normal tissue damage and improving tumor control in
radiation therapy. Irradiation activates endothelial cells which then participate
in the recruitment of circulating cells, especially by overexpressing cell
adhesion molecules, but also by other as yet unknown mechanisms. Since protein
glycosylation is an important determinant of cell adhesion, we hypothesized that
radiation could alter the glycosylation pattern of endothelial cells and thereby
impact adhesion of circulating cells. Herein, we show that ionizing radiation
increases high mannose-type N-glycans and decreases glycosaminoglycans. These
changes stimulate interactions measured under flow conditions between irradiated
endothelial cells and monocytes. Targeted transcriptomic approaches in vitro in
endothelial cells and in vivo in a radiation enteropathy mouse model confirm that
genes involved in N- and O-glycosylation are modulated by radiation, and in
silico analyses give insight into the mechanism by which radiation modifies
glycosylation. The endothelium glycome may therefore be considered as a key
therapeutic target for modulating the chronic inflammatory response observed in
healthy tissues or for participating in tumor control by radiation therapy.
PMID- 28706281
TI - Thiamine metabolism is critical for regulating correlated growth of dendrite
arbors and neuronal somata.
AB - Thiamine is critical for cellular function, as its phosphorylated and active
form, thiamine diphosphate (TDP), acts as coenzyme for three key enzymes in
glucose metabolism. Mutations in thiamine transporter, TDP synthesizing enzyme or
carrier, including solute carrier family 19 member 3 (SLC19A3), thiamine
pyrophosphokinase (TPK1) and solute carrier family 25 member 19 (SLC25A19), have
been associated with developmental neurological disorders, including microcephaly
and Leigh syndrome. However, little is known about how thiamine metabolism
regulates neuronal morphology at the cellular level. Here, using primary rat
hippocampal neuronal cultures, we showed that reducing the expression of Tpk1,
Slc25a19 or Slc19a3 in individual neurons significantly reduced dendrite
complexity, as measured by total dendritic branch tip number (TDBTN) and total
dendritic branch length (TDBL). The specificity of the RNAi effects were verified
by overexpression of RNAi resistant human constructs. Importantly, changes in
both TDBTN and TDBL tightly correlated with reduction in soma size, demonstrating
coordinated regulation of soma and dendrite growth by thiamine. The requirement
of thiamine metabolism for coordinated somata and dendrite growth is highly
consistent with the microcephaly and neurodegenerative phenotypes observed in
thiamine loss-of-function diseases.
PMID- 28706282
TI - Retinal degeneration in progressive supranuclear palsy measured by optical
coherence tomography and scanning laser polarimetry.
AB - This cross-sectional study compared the retinal morphology between patients with
progressive supranuclear palsy (PSP) and healthy controls. (The retinal nerve
fiber layer (RNFL) around the optic disc and the retina in the macular area of 22
PSP patients and 151 controls were investigated by spectral domain optical
coherence tomography (SD-OCT). Additionally, the RNFL and the nerve fiber index
(NFI) were measured by scanning laser polarimetry (SLP). Results of RNFL
measurements with SD-OCT and SLP were compared to assess diagnostic
discriminatory power. Applying OCT, PSP patients showed a smaller RNFL thickness
in the inferior nasal and inferior temporal areas. The macular volume and the
thickness of the majority of macular sectors were reduced compared to controls.
SLP data showed a thinner RNFL thickness and an increase in the NFI in PSP
patients. Sensitivity and specificity to discriminate PSP patients from controls
were higher applying SLP than SD-OCT. Retinal changes did not correlate with
disease duration or severity in any OCT or SLP measurement. PSP seems to be
associated with reduced thickness and volume of the macula and reduction of the
RNFL, independent of disease duration or severity. Retinal imaging with SD-OCT
and SLP might become an additional tool in PSP diagnosis.
PMID- 28706283
TI - Structure of polyhydroxyalkanoate (PHA) synthase PhaC from Chromobacterium sp.
USM2, producing biodegradable plastics.
AB - Polyhydroxyalkanoate (PHA) is a promising candidate for use as an alternative
bioplastic to replace petroleum-based plastics. Our understanding of PHA synthase
PhaC is poor due to the paucity of available three-dimensional structural
information. Here we present a high-resolution crystal structure of the catalytic
domain of PhaC from Chromobacterium sp. USM2, PhaC Cs -CAT. The structure shows
that PhaC Cs -CAT forms an alpha/beta hydrolase fold comprising alpha/beta core
and CAP subdomains. The active site containing Cys291, Asp447 and His477 is
located at the bottom of the cavity, which is filled with water molecules and is
covered by the partly disordered CAP subdomain. We designated our structure as
the closed form, which is distinct from the recently reported catalytic domain
from Cupriavidus necator (PhaC Cn -CAT). Structural comparison showed PhaC Cn
CAT adopting a partially open form maintaining a narrow substrate access channel
to the active site, but no product egress. PhaC Cs -CAT forms a face-to-face
dimer mediated by the CAP subdomains. This arrangement of the dimer is also
distinct from that of the PhaC Cn -CAT dimer. These findings suggest that the CAP
subdomain should undergo a conformational change during catalytic activity that
involves rearrangement of the dimer to facilitate substrate entry and product
formation and egress from the active site.
PMID- 28706284
TI - Facile fabrication of superparamagnetic graphene/polyaniline/Fe3O4 nanocomposites
for fast magnetic separation and efficient removal of dye.
AB - Using graphene as adsorbent for removal of pollutants from polluted water is
commonly recognized to be costly because the graphene is usually produced by a
very complex process. Herein, a simple and eco-friendly method was employed to
fabricate efficient superparamagnetic graphene/polyaniline/Fe3O4 nanocomposites
for removal of dyes. The exfoliation of graphite as nanosheets and the
functionalization of nanosheets with polyaniline and Fe3O4 nanoparticles were
simultaneously achieved via a one-pot reaction process combining the
intercalation polymerization of aniline and the co-precipitation of the residual
Fe3+ and the generated Fe2+. The obtained graphene/polyaniline/Fe3O4
nanocomposites exhibited excellent adsorption performance for Congo red, even in
the presence of Brilliant green. The adsorption kinetics and adsorption isotherms
were well fitted with pseudo second-order kinetic model and Langmuir isotherm
model, respectively. In a word, this method is simple and industrially feasible,
which provides a new approach to fabricate highly efficient graphene-based
adsorbents on large scale for removal of dyes. In addition, it also can be used
to exfoliate other two-dimensional materials, such as boron nitride, carbon
nitride and MoS2 for a range of possible applications.
PMID- 28706285
TI - Transcriptional Regulation of Cellulose Biosynthesis during the Early Phase of
Nitrogen Deprivation in Nannochloropsis salina.
AB - Microalgal photosynthesis provides energy and carbon-containing precursors for
the biosynthesis of storage carbohydrates such as starch, chrysolaminarin,
lipids, and cell wall components. Under mild nitrogen deficiency (N-), some
Nannochloropsis species accumulate lipid by augmenting cytosolic fatty acid
biosynthesis with a temporary increase in laminarin. Accordingly, biosynthesis of
the cellulose-rich cell wall should change in response to N- stress because this
biosynthetic pathway begins with utilisation of the hexose phosphate pool
supplied from photosynthesis. However, few studies have characterised microalgal
cell wall metabolism, including oleaginous Nannochloropsis sp. microalgae
subjected to nitrogen deficiency. Here, we investigated N-induced changes in
cellulose biosynthesis in N. salina. We observed that N- induced cell wall
thickening, concurrently increased the transcript levels of genes coding for UDPG
pyrophosphorylase and cellulose synthases, and increased cellulose content.
Nannochloropsis salina cells with thickened cell wall were more susceptible to
mechanical stress such as bead-beating and sonication, implicating cellulose
metabolism as a potential target for cost-effective microalgal cell disruption.
PMID- 28706286
TI - Corrigendum: Glacial isostatic uplift of the European Alps.
AB - This corrects the article DOI: 10.1038/ncomms13382.
PMID- 28706287
TI - Association of wall shear stress with intracranial aneurysm rupture: systematic
review and meta-analysis.
AB - To evaluate the relationship between wall shear stress (WSS) magnitude and
cerebral aneurysm rupture and provide new insight into the disparate
computational fluid dynamics (CFD) findings concerning the role of WSS in
intracranial aneurysm (IA) rupture. A systematic electronic database (PubMed,
Medline, Springer, and EBSCO) search was conducted for all accessible published
articles up to July 1, 2016, with no restriction on the publication year.
Abstracts, full-text manuscripts, and the reference lists of retrieved articles
were analyzed. Random effects meta-analysis was used to pool the complication
rates across studies. Twenty-two studies containing CFD data on 1257 patients
with aneurysms were included in the analysis. A significantly higher rate of low
WSS (0-1.5 Pa) was found in ruptured aneurysms (odds ratio [OR] 2.17; 95%
confidence interval [CI], 1.73-2.62). The pooled analyses across 14 studies with
low WSS showed significantly lower mean WSS (0.64 vs. 1.4 Pa) (p = 0.037) in the
ruptured group. This meta-analysis provides evidence that decreased local WSS may
be an important predictive parameter of IA rupture.
PMID- 28706288
TI - Spinal pathways involved in somatosensory inhibition of the psychomotor actions
of cocaine.
AB - Previous studies have demonstrated that somatosensory stimuli influence dopamine
transmission in the mesolimbic reward system and can reduce drug-induced motor
behaviors, craving and dependence. Until now, the central links between
somatosensory and brain reward systems are not known. Here, we show that the
dorsal column (DC) somatosensory pathway contains projections that convey an
inhibitory input from the periphery to mesolimbic reward circuits. Stimulation of
the ulnar nerve under HT7 acupoint suppressed psychomotor response to cocaine,
which was abolished by disruption of the DC pathway, but not the spinothalamic
tract (STT). Low-threshold or wide-dynamic range neurons in the cuneate nucleus
(CN) were excited by peripheral stimulation. Lesions of dorsal column or lateral
habenula (LHb) prevented the inhibitory effects of peripheral stimulation on
cocaine-induced neuronal activation in the nucleus accumbens (NAc). LHb neurons
projecting to the ventral tegmental area (VTA)/rostromedial tegmental nucleus
(RMTg) regions were activated by peripheral stimulation and LHb lesions reversed
the inhibitory effects on cocaine locomotion produced by peripheral stimulation.
These findings suggest that there exists a pathway in spinal cord that ascends
from periphery to mesolimbic reward circuits (spino-mesolimbic pathway) and the
activation of somatosensory input transmitted via the DC pathway can inhibit the
psychomotor response to cocaine.
PMID- 28706289
TI - Hydrogen self-diffusion in single crystal olivine and electrical conductivity of
the Earth's mantle.
AB - Nominally anhydrous minerals formed deep in the mantle and transported to the
Earth's surface contain tens to hundreds of ppm wt H2O, providing evidence for
the presence of dissolved water in the Earth's interior. Even at these low
concentrations, H2O greatly affects the physico-chemical properties of mantle
materials, governing planetary dynamics and evolution. The diffusion of hydrogen
(H) controls the transport of H2O in the Earth's upper mantle, but is not fully
understood for olivine ((Mg, Fe)2SiO4) the most abundant mineral in this region.
Here we present new hydrogen self-diffusion coefficients in natural olivine
single crystals that were determined at upper mantle conditions (2 GPa and 750
900 degrees C). Hydrogen self-diffusion is highly anisotropic, with values at
900 degrees C of 10-10.9, 10-12.8 and 10-11.9 m2/s along [100], [010] and [001]
directions, respectively. Combined with the Nernst-Einstein relation, these
diffusion results constrain the contribution of H to the electrical conductivity
of olivine to be sigmaH = 102.12S/m.CH2O.exp-187kJ/mol/(RT). Comparisons between
the model presented in this study and magnetotelluric measurements suggest that
plausible H2O concentrations in the upper mantle (<=250 ppm wt) can account for
high electrical conductivity values (10-2-10-1 S/m) observed in the
asthenosphere.
PMID- 28706290
TI - Dramatically Enhanced Spin Dynamo with Plasmonic Diabolo Cavity.
AB - The applications of spin dynamos, which could potentially power complex
nanoscopic devices, have so far been limited owing to their extremely low energy
conversion efficiencies. Here, we present a unique plasmonic diabolo cavity (PDC)
that dramatically improves the spin rectification signal (enhancement of more
than three orders of magnitude) under microwave excitation; further, it enables
an energy conversion efficiency of up to ~0.69 mV/mW, compared with ~0.27 MUV/mW
without a PDC. This remarkable improvement arises from the simultaneous
enhancement of the microwave electric field (~13-fold) and the magnetic field
(~195-fold), which cooperate in the spin precession process generates
photovoltage (PV) efficiently under ferromagnetic resonance (FMR) conditions. The
interplay of the microwave electromagnetic resonance and the ferromagnetic
resonance originates from a hybridized mode based on the plasmonic resonance of
the diabolo structure and Fabry-Perot-like modes in the PDC. Our work sheds light
on how more efficient spin dynamo devices for practical applications could be
realized and paves the way for future studies utilizing both artificial and
natural magnetism for applications in many disciplines, such as for the design of
future efficient wireless energy conversion devices, high frequent resonant
spintronic devices, and magnonic metamaterials.
PMID- 28706291
TI - Structural and functional characterization of a DARPin which inhibits Ras
nucleotide exchange.
AB - Ras mutations are the oncogenic drivers of many human cancers and yet there are
still no approved Ras-targeted cancer therapies. Inhibition of Ras nucleotide
exchange is a promising new approach but better understanding of this mechanism
of action is needed. Here we describe an antibody mimetic, DARPin K27, which
inhibits nucleotide exchange of Ras. K27 binds preferentially to the inactive Ras
GDP form with a Kd of 4 nM and structural studies support its selectivity for
inactive Ras. Intracellular expression of K27 significantly reduces the amount of
active Ras, inhibits downstream signalling, in particular the levels of
phosphorylated ERK, and slows the growth in soft agar of HCT116 cells. K27 is a
potent, non-covalent inhibitor of nucleotide exchange, showing consistent effects
across different isoforms of Ras, including wild-type and oncogenic mutant forms.
PMID- 28706292
TI - Genome-wide survey indicates diverse physiological roles of the barley (Hordeum
vulgare L.) calcium-dependent protein kinase genes.
AB - Calcium-dependent protein kinases (CDPKs) are crucial calcium sensors that play
important roles in the regulation of plant growth and developmental processes, as
well as protective responses to environmental stress. Here, we identified 28 CDPK
genes from barley and cloned 5 new, full-length CDPK genes, MLOC_58648a,
MLOC_19618a, MLOC_71733a, AK249361a and MLOC_4965a, using their expressed
sequence tags. Phylogenetic and gene structural analyses revealed that the CDPK
could be divided into four subgroups. Significant site-specific altered
constraints and a high evolutionary rate may have contributed to the functional
divergences among CDPK gene subfamilies. Expression profiles of different tissues
and developmental stages suggested that several CDPK genes are involved in the
functional development of plants. Different expression levels under a variety of
abiotic stresses also indicated that the CDPK family underwent functional
divergence during long-term evolution. Furthermore, several CDPK genes responded
to single treatments and individual CDPK genes responded to multiple treatments,
suggesting that barley CDPKs may be involved in mediating cross-talk among
different signalling pathways. Our data provide an important foundation for the
functional and evolutionary analyses of this important gene family in barley.
PMID- 28706293
TI - Small cell lung cancer: model of circulating tumor cell tumorospheres in
chemoresistance.
AB - Small cell lung cancer (SCLC) represents 15% of lung cancers and is characterized
by early dissemination, development of chemoresistance and a poor prognosis. A
host of diverse drugs failed invariably and its mechanisms of global
chemoresistance have not been characterized so far. SCLC represents the prototype
of an aggressive and highly metastatic tumor which is ultimately refractory to
any treatment. High numbers of circulating tumor cells (CTCs) allowed us to
establish 5 CTC cell lines (BHGc7, 10, 16, 26 and UHGc5) from patients with
recurrent SCLC. These cell lines exhibit the typical SCLC markers and CTCs of all
patients developed spontaneously large multicellular aggregates, termed
tumorospheres. Ki67 and carbonic anhydrase 9 (CAIX) staining of tumorosphere
sections revealed quiescent and hypoxic cells, respectively. Accordingly,
comparison of the chemosensitivity of CTC single cell suspensions with
tumorospheres demonstrated increased resistance of the clusters against
chemotherapeutics commonly used for treatment of SCLC. Therefore, global
chemoresistance of relapsing SCLC seems to rely on formation of large
tumorospheres which reveal limited accessibility, lower growth fraction and
hypoxic conditions. Since similar tumor spheroids were found in other tumor
types, SCLC seems to represent a unique tumor model to study the association of
CTCs, metastasis and drug resistance.
PMID- 28706294
TI - Assessment of occlusion with the T-Scan system in patients undergoing
orthognathic surgery.
AB - Dental occlusion varies among individuals, and achieving correct physiological
occlusion after osteotomy is essential for the complex functioning of the
stomatognathic system. The T-Scan system records the centre of force, first
contact, maximum bite force, and maximum intercuspation. The aim of the present
study was to investigate the usefulness and consistency of T-Scan in assessing
occlusion before and after orthognathic surgery. Occlusal information was
evaluated for 30 healthy adults with normal occlusion and 40 patients undergoing
orthognathic surgery. T-Scan had a high degree of reliability for consecutive
measurements (Pearson correlation, r = 0.98). For most parameters, occlusal
distribution was better after surgery than before surgery. More teeth contributed
to occlusion at maximum intercuspation after surgery than before surgery (14 vs.
10). In addition, the difference in the posterior force distribution was reduced
after surgery (17.6 +/- 13.8 vs. 22.7 +/- 21.4 before surgery), indicating better
occlusal force distribution after surgery. The maximum percentage force on teeth
(p = 0.004) and the number of teeth contributing to occlusion (p < 0.001) also
differed significantly. Thus, T-Scan is good for assessing occlusal discrepancies
and can be used to portray the pre- and post-operative occlusal contact
distribution during treatment planning and follow-up.
PMID- 28706295
TI - DGKdelta triggers endoplasmic reticulum release of IFT88-containing vesicles
destined for the assembly of primary cilia.
AB - The morphogenic factor Sonic hedgehog (Shh) signals through the primary cilium,
which relies on intraflagellar transport to maintain its structural integrity and
function. However, the process by which protein and lipid cargos are delivered to
the primary cilium from their sites of synthesis still remains poorly
characterized. Here, we report that diacylglycerol kinase delta (DGKdelta), a
residential lipid kinase in the endoplasmic reticulum, triggers the release of
IFT88-containing vesicles from the ER exit sites (ERES), thereby setting forth
their movement to the primary cilium. Encoded by the gene whose mutations
originally implicated the primary cilium as the venue of Shh signaling, IFT88 is
known to be part of the complex B that drives the anterograde transport within
cilia. We show that IFT88 interacts with DGKdelta, and is associated with COPII
coated vesicles at the ERES. Using a combination of RNAi silencing and gene
knockout strategies, we further show that DGKdelta is required for supporting Shh
signaling both in vitro and in vivo, demonstrating the physiological significance
of this regulation.
PMID- 28706296
TI - 4-alkyl-L-(Dehydro)proline biosynthesis in actinobacteria involves N-terminal
nucleophile-hydrolase activity of gamma-glutamyltranspeptidase homolog for C-C
bond cleavage.
AB - gamma-Glutamyltranspeptidases (gamma-GTs), ubiquitous in glutathione metabolism
for gamma-glutamyl transfer/hydrolysis, are N-terminal nucleophile (Ntn)
hydrolase fold proteins that share an autoproteolytic process for self
activation. gamma-GT homologues are widely present in Gram-positive
actinobacteria where their Ntn-hydrolase activities, however, are not involved in
glutathione metabolism. Herein, we demonstrate that the formation of 4-Alkyl-L
(dehydro)proline (ALDP) residues, the non-proteinogenic alpha-amino acids that
serve as vital components of many bioactive metabolites found in actinobacteria,
involves unprecedented Ntn-hydrolase activity of gamma-GT homologue for C-C bond
cleavage. The related enzymes share a key Thr residue, which acts as an internal
nucleophile for protein hydrolysis and then as a newly released N-terminal
nucleophile for carboxylate side-chain processing likely through the generation
of an oxalyl-Thr enzyme intermediate. These findings provide mechanistic insights
into the biosynthesis of various ALDP residues/associated natural products,
highlight the versatile functions of Ntn-hydrolase fold proteins, and
particularly generate interest in thus far less-appreciated gamma-GT homologues
in actinobacteria.
PMID- 28706297
TI - Harmless effects of argon plasma on caudal fin regeneration and embryogenesis of
zebrafish: novel biological approaches for safe medical applications of
bioplasma.
AB - The argon plasma jet (Ar-PJ) is widely used in medical fields such as dermatology
and dentistry, and it is considered a promising tool for cancer therapy. However,
the in vivo effects of Ar-PJ for medical uses have not yet been investigated, and
there are no biological tools to determine the appropriate clinical dosages of Ar
PJ. In this study, we used the caudal fin and embryo of zebrafish as novel in
vivo tools to evaluate the biosafety of Ar-PJ. Typically, Ar-PJ is known to
induce cell death in two-dimensional (2D) cell culture systems. By contrast, no
detrimental effects of Ar-PJ were shown in our 3D zebrafish systems composed of
2D cells. The Ar-PJ-treated caudal fins grew by an average length of 0.7 mm,
similar to the length of the normally regenerating fins. Remarkably, Ar-PJ did
not affect the expression patterns of Wnt8a and beta-Catenin, which play
important roles in fin regeneration. In the embryo system, 85% of the Ar-PJ
treated embryos hatched, and the lateral length of these embryos was ~3.3 mm,
which are equivalent to the lengths of normal embryos. In particular,
vasculogenesis, which is the main cellular process during tissue regeneration and
embryogenesis, occurred normally under the Ar-PJ dose used in this study.
Therefore, our biosafety evaluation tools that use living model systems can be
used to provide an experimental guideline to determine the clinically safe dosage
of Ar-PJ.
PMID- 28706298
TI - CKAP2 phosphorylation by CDK1/cyclinB1 is crucial for maintaining centrosome
integrity.
AB - Previously, we have reported that CKAP2 is involved in the maintenance of
centrosome integrity, thus allowing for proper mitosis in primary hepatocytes. To
understand this biological process, we identified the mitosis-specific
phosphorylation sites in mouse CKAP2 and investigated CKAP's possible role in
cell cycle progression. Because we observed mouse CKAP2 depletion in amplified
centrosomes and aberrant chromosomal segregation, which was rescued by ectopic
expression of wild-type CKAP2, we focused on the centrosome duplication process
among the various aspects of the cell cycle. Among the identified phosphorylation
sites, T603 and possibly S608 were phosphorylated by CDK1-cyclin B1 during
mitosis, and the ectopic expression of both T603A and S608A mutants was unable to
restore the centrosomal abnormalities in CKAP2-depleted cells. These results
indicated that the phosphorylation status of CKAP2 during mitosis is critical for
controlling both centrosome biogenesis and bipolar spindle formation.
PMID- 28706299
TI - Findings of a 1303 Korean whole-exome sequencing study.
AB - Ethnically specific data on genetic variation are crucial for understanding human
biology and for clinical interpretation of variant pathogenicity. We analyzed
data obtained by deep sequencing 1303 Korean whole exomes; the data were
generated by three independent whole exome sequencing projects (named the KOEX
study). The primary focus of this study was to comprehensively analyze the
variant statistics, investigate secondary findings that may have clinical
actionability, and identify loci that should be cautiously interpreted for
pathogenicity. A total of 495 729 unique variants were identified at exonic
regions, including 169 380 nonsynonymous variants and 4356 frameshift
insertion/deletions. Among these, 76 607 were novel coding variants. On average,
each individual had 7136 nonsynonymous single-nucleotide variants and 74
frameshift insertion/deletions. We classified 13 pathogenic and 13 likely
pathogenic variants in 56 genes that may have clinical actionability according to
the guidelines of the American College of Medical Genetics and Genomics, and the
Association for Molecular Pathology. The carrier frequency of these 26 variants
was 2.46% (95% confidence interval 1.73-3.46). To identify loci that require
cautious interpretation in clinical sequencing, we identified 18 genes that are
prone to sequencing errors, and 671 genes that are highly polymorphic and carry
excess nonsynonymous variants. The catalog of identified variants, its annotation
and frequency information are publicly available (http://koex.snu.ac.kr). These
findings should be useful resources for investigating ethnically specific
characteristics in human health and disease.
PMID- 28706300
TI - Genetic analyses reveal independent domestication origins of the emerging oil
crop Paeonia ostii, a tree peony with a long-term cultivation history.
AB - Paeonia ostii, a member of tree peony, is an emerging oil crop with important
medical and oil uses and widely cultivated in China. Dissolving the genetic
diversity and domestication history of this species is important for further
genetic improvements and deployments. We firstly selected 29 simple sequence
repeats (SSRs) via transcriptome mining, segregation analyses and polymorphism
characterizations; then, 901 individuals from the range-wide samples were
genotyped using well-characterized SSR markers. We observed moderate genetic
diversity among individuals, and Shaanxi Province was identified as the center of
genetic diversity for our cultivated plants. Five well-separated gene pools were
detected by STRUCTURE analyses, and the results suggested that multiple
independent domestication origins occurred in Shaanxi Province and Tongling City
(Anhui Province). Taken together, the genetic evidence and the historical records
suggest multiple long-distance introductions after the plant was domesticated in
Shandong, Henan and Hunan provinces. The present study provides the first genetic
evaluation of the domestication history of P. ostii, and our results provide an
important reference for further genetic improvements and deployments of this
important crop.
PMID- 28706301
TI - A Haystack Heuristic for Autoimmune Disease Biomarker Discovery Using Next-Gen
Immune Repertoire Sequencing Data.
AB - Large-scale DNA sequencing of immunological repertoires offers an opportunity for
the discovery of novel biomarkers for autoimmune disease. Available
bioinformatics techniques however, are not adequately suited for elucidating
possible biomarker candidates from within large immunosequencing datasets due to
unsatisfactory scalability and sensitivity. Here, we present the Haystack
Heuristic, an algorithm customized to computationally extract disease-associated
motifs from next-generation-sequenced repertoires by contrasting disease and
healthy subjects. This technique employs a local-search graph-theory approach to
discover novel motifs in patient data. We apply the Haystack Heuristic to nine
million B-cell receptor sequences obtained from nearly 100 individuals in order
to elucidate a new motif that is significantly associated with multiple
sclerosis. Our results demonstrate the effectiveness of the Haystack Heuristic in
computing possible biomarker candidates from high throughput sequencing data and
could be generalized to other datasets.
PMID- 28706302
TI - Mercury spikes suggest volcanic driver of the Ordovician-Silurian mass
extinction.
AB - The second largest Phanerozoic mass extinction occurred at the Ordovician
Silurian (O-S) boundary. However, unlike the other major mass extinction events,
the driver for the O-S extinction remains uncertain. The abundance of mercury
(Hg) and total organic carbon (TOC) of Ordovician and early Silurian marine
sediments were analyzed from four sections (Huanghuachang, Chenjiahe, Wangjiawan
and Dingjiapo) in the Yichang area, South China, as a test for evidence of
massive volcanism associated with the O-S event. Our results indicate the Hg
concentrations generally vary in parallel with TOC, and that the Hg/TOC ratios
remain low and steady state through the Early and Middle Ordovician. However, Hg
concentrations and the Hg/TOC ratio increased rapidly in the Late Katian, and
have a second peak during the Late Hirnantian (Late Ordovician) that was
temporally coincident with two main pulses of mass extinction. Hg isotope data
display little to no variation associated with the Hg spikes during the
extinction intervals, indicating that the observed Hg spikes are from a volcanic
source. These results suggest intense volcanism occurred during the Late
Ordovician, and as in other Phanerozoic extinctions, likely played an important
role in the O-S event.
PMID- 28706303
TI - Memristive neural network for on-line learning and tracking with brain-inspired
spike timing dependent plasticity.
AB - Brain-inspired computation can revolutionize information technology by
introducing machines capable of recognizing patterns (images, speech, video) and
interacting with the external world in a cognitive, humanlike way. Achieving this
goal requires first to gain a detailed understanding of the brain operation, and
second to identify a scalable microelectronic technology capable of reproducing
some of the inherent functions of the human brain, such as the high synaptic
connectivity (~104) and the peculiar time-dependent synaptic plasticity. Here we
demonstrate unsupervised learning and tracking in a spiking neural network with
memristive synapses, where synaptic weights are updated via brain-inspired spike
timing dependent plasticity (STDP). The synaptic conductance is updated by the
local time-dependent superposition of pre- and post-synaptic spikes within a
hybrid one-transistor/one-resistor (1T1R) memristive synapse. Only 2 synaptic
states, namely the low resistance state (LRS) and the high resistance state
(HRS), are sufficient to learn and recognize patterns. Unsupervised learning of a
static pattern and tracking of a dynamic pattern of up to 4 * 4 pixels are
demonstrated, paving the way for intelligent hardware technology with up-scaled
memristive neural networks.
PMID- 28706304
TI - Intrinsic Enhancement of Dielectric Permittivity in (Nb + In) co-doped TiO2
single crystals.
AB - The development of dielectric materials with colossal permittivity is important
for the miniaturization of electronic devices and fabrication of high-density
energy-storage devices. The electron-pinned defect-dipoles has been recently
proposed to boost the permittivity of (Nb + In) co-doped TiO2 to 105. However,
the follow-up studies suggest an extrinsic contribution to the colossal
permittivity from thermally excited carriers. Herein, we demonstrate a marked
enhancement in the permittivity of (Nb + In) co-doped TiO2 single crystals at
sufficiently low temperatures such that the thermally excited carriers are frozen
out and exert no influence on the dielectric response. The results indicate that
the permittivity attains quadruple of that for pure TiO2. This finding suggests
that the electron-pinned defect-dipoles add an extra dielectric response to that
of the TiO2 host matrix. The results offer a novel approach for the development
of functional dielectric materials with large permittivity by engineering complex
defects into bulk materials.
PMID- 28706305
TI - Pressure-Induced Crystallization and Phase Transformation of Para-xylene.
AB - Static pressure is an alternative method to chemical pressure for tuning the
crystal structure, bonds, and physical properties of materials, and is a
significant technique for the synthesis of novel materials and fundamental
research. In this letter, we report the crystallization and phase transformation
of p-xylene under high pressure. Our optical micrographic observations and the
appearance of lattice modes in the Raman and infrared (IR) spectra indicated that
p-xylene crystallizes at ~0.1 GPa. The X-ray diffraction (XRD) pattern at 0.84
GPa suggests that the crystallized p-xylene had a monoclinic phase with the Cc(9)
space group. The sharp shrinkage of the lattice at ~13 GPa and the solid state of
the decompressed sample we observed suggests a new crystalline phase of p-xylene.
The in situ XRD showed that the new crystalline phase was still a monoclinic
structure but with a different space group of C2(5), indicating that a phase
transition occurred during further compression. The mass spectrometry experiment
confirmed phase transition polymerization, with mainly trimer and tetramer
polymers. Our findings suggest an easy and efficient method for crystallizing and
polymerizing p-xylene under high pressure.
PMID- 28706306
TI - Ligand-induced type II interleukin-4 receptor dimers are sustained by rapid re
association within plasma membrane microcompartments.
AB - The spatiotemporal organization of cytokine receptors in the plasma membrane is
still debated with models ranging from ligand-independent receptor pre
dimerization to ligand-induced receptor dimerization occurring only after
receptor uptake into endosomes. Here, we explore the molecular and cellular
determinants governing the assembly of the type II interleukin-4 receptor, taking
advantage of various agonists binding the receptor subunits with different
affinities and rate constants. Quantitative kinetic studies using artificial
membranes confirm that receptor dimerization is governed by the two-dimensional
ligand-receptor interactions and identify a critical role of the transmembrane
domain in receptor dimerization. Single molecule localization microscopy at
physiological cell surface expression levels, however, reveals efficient ligand
induced receptor dimerization by all ligands, largely independent of receptor
binding affinities, in line with the similar STAT6 activation potencies observed
for all IL-4 variants. Detailed spatiotemporal analyses suggest that kinetic
trapping of receptor dimers in actin-dependent microcompartments sustains robust
receptor dimerization and signalling.
PMID- 28706307
TI - Effect of Shock-Induced Cavitation Bubble Collapse on the damage in the Simulated
Perineuronal Net of the Brain.
AB - The purpose of this study is to conduct modeling and simulation to understand the
effect of shock-induced mechanical loading, in the form of cavitation bubble
collapse, on damage to the brain's perineuronal nets (PNNs). It is known that
high-energy implosion due to cavitation collapse is responsible for corrosion or
surface damage in many mechanical devices. In this case, cavitation refers to the
bubble created by pressure drop. The presence of a similar damage mechanism in
biophysical systems has long being suspected but not well-explored. In this
paper, we use reactive molecular dynamics (MD) to simulate the scenario of a
shock wave induced cavitation collapse within the perineuronal net (PNN), which
is the near-neuron domain of a brain's extracellular matrix (ECM). Our model is
focused on the damage in hyaluronan (HA), which is the main structural component
of PNN. We have investigated the roles of cavitation bubble location, shockwave
intensity and the size of a cavitation bubble on the structural evolution of PNN.
Simulation results show that the localized supersonic water hammer created by an
asymmetrical bubble collapse may break the hyaluronan. As such, the current study
advances current knowledge and understanding of the connection between PNN damage
and neurodegenerative disorders.
PMID- 28706309
TI - The Draft Genome of Globodera ellingtonae.
AB - Globodera ellingtonae is a newly described potato cyst nematode (PCN) found in
Idaho, Oregon, and Argentina. Here, we present a genome assembly for G.
ellingtonae, a relative of the quarantine nematodes G. pallida and G.
rostochiensis, produced using data from Illumina and Pacific Biosciences DNA
sequencing technologies.
PMID- 28706310
TI - Draft Transcriptome of Globodera ellingtonae.
AB - Globodera ellingtonae is a newly described cyst nematode found in Idaho, Oregon,
and Argentina. Here we present the first transcriptome assembly of G.
ellingtonae, providing a valuable resource for comparing the evolution of
expressed genes between potato cyst nematode species.
PMID- 28706311
TI - First Report of the Fig Cyst Nematode, Heterodera fici Kirjanova, on Fig Tree,
Ficus carica, in Ontario, Canada.
AB - Although fig trees are a popular ornamental fruit tree in subtropical regions,
some hardy species, such as Ficus carica, have been grown in the west coast of
British Columbia and southern Ontario in Canada. The fig cyst nematode,
Heterodera fici Kirjanova, is a pest on fig plants, and the heavy infestation can
cause retarded growth and yellowing of leaves (Maqbool et al., 1987). In the
spring of 2016, a sample of rhizosphere from a potted fig (F. carica) seedling
was submitted to the Nematology Laboratory, Canadian Food Inspection Agency. The
sample was collected from a nursery in Niagara-on-the-Lake, Ontario, Canada,
during an inspection to support export certification. The fig trees in the
nursery had been grown in the outside fields during the growing seasons and
potted and moved to indoor during the winters for last 3 years. The sample was
subjected to a nematode extraction process, including decanting and sieving and
misting, and lemon-shaped cysts and second-stage juveniles of Heterodera sp. were
recovered from the sample examined. The morphological and molecular analyses of
the cysts, vulval cone, and second-stage juveniles from both the roots and the
crushed cysts identified the species as Heterodera fici Kirjanova. The cysts were
characterized by their dark brown color and lemon shape, as well as distinct
necks and vulval cones. The vulval cones were observed having an ambifenestrate
fenestra (Fig. 1AFig. 1Photomicrographs of Heterodera fici on fig tree from
Ontario, Canada. A, B. Cyst vulval cones with the ambifenestrate fenestra in A)
and well-developed underbridge and bullae in B). C-E. The second-stage juveniles
from a crushed cyst with the whole body in C), the anterior region in D) and the
posterior region in E).), dome-shaped bullae scattered around the underbridge
plane (Fig. 1B), well-developed underbridge (Fig. 1B), and coarse zig-zag ridges
surrounding the fenestra on the surface. The cyst measurements (n = 3) were
length 608.7 +/- 91.6 (506-682) um, width = 395.3 +/- 40.9 (366-442) um, and
length/width ratio = 1.3 +/- 0.2 (1.3-1.7) um. The morphometric characters of the
vulval cone were fenestral length = 57.3 +/- 2.9 (54-59) um, fenestral width =
35.3 +/- 4 (33-40) um, and vulval slit = 50.7 +/- 1.2 (50-52) um. Second-stage
juveniles tapering posteriorly (Fig. 1C). Stylet well developed, basal knobs
rounded, directed slightly anteriorly (Fig. 1D). Tail tapering, with hyaline
terminal about half of tail length (Fig. 1E). Second-stage juveniles (n = 16)
showed the following morphometric characters: body length = 440.9 +/- 20 (408
470) um, a = 20.3 +/- 2.3 (16.9-24), b = 2.7 +/- 0.3 (2.3-3.3), c = 8.1 +/- 0.6
(7.3-9.3), c' = 3.8 +/- 0.3 (3.1-4.3), stylet length = 23.2 +/- 0.4 (23-24) um,
anterior end to median bulb = 71.8 +/- 4.5 (65-79) um; maximum body width = 21.9
+/- 2 (17-25) um; body width at anus = 14.4 +/- 1.5 (12-17) um, tail length =
54.6 +/- 2.9 (50-60) um, and hyaline part of tail = 23.7 +/- 2.9 (19-28) um.
These observations conform to the published descriptions of Heterodera fici
Kirjanova (Kirjanova, 1954; Golden et al., 1988). The slides of the cyst vulval
cone and juveniles were deposited in the Canadian National collection of Insects,
Arachnids, and Nematodes (Accession no. 14851 to 14853 for the second stage
juveniles and 14854-14855 for the cyst cones). For molecular analysis, DNA was
extracted from individual juvenile (n = 4) from different cysts. A 1,151-bp
fragment of ribosomal DNA containing ITS1-5.8S-ITS2 region was amplified and
sequenced using primers 18S (5'-TTGATTACGTCCCTGCCCTTT-3') and 26S (5'-
TTTCACTCGCCGTTACTAAGG-3') (Vrain et al., 1992). The sequence was deposited into
the GenBank database (Accession no. KY635986 and KY635987) and was compared with
published sequences by means of BLAST search in the database (November 2016). The
comparison revealed 99.0% to 100% similarity to the sequences of the same genomic
region of H. fici from Iran (AF498385) and Georgia (AF274409). Subbotin et al.
(2010) summarized the known occurrence of the fig cyst nematode from Belarus,
Belgium, Estonia, France, Germany, Greece, Hungary, Italy, The Netherlands,
Norway, Poland, Portugal, Russia, Spain, Yugoslavia, China, Georgia, Iran,
Turkey, Uzbekistan, Australia, New Zealand, United States (California, Florida,
Louisiana, Maryland, and Virginia), Brazil, Algeria, and South Africa. It is an
exotic pest to Canada. To our knowledge, this is the first evidence of the
occurrence of H. fici in Canada.
PMID- 28706312
TI - Management of Root-knot Nematode (Meloidogyne incognita) on Pittosporum tobira
Under Greenhouse, Field, and On-farm Conditions in Florida.
AB - Root-knot nematodes are important pests of cut foliage crops in Florida.
Currently, effective nematicides for control of these nematodes on cut foliage
crops are lacking. Hence, research was conducted at the University of Florida to
identify pesticides or biopesticides that could be used to manage these
nematodes. The research comprised on-farm, field, and greenhouse trials.
Nematicide treatments evaluated include commercial formulations of spirotetramat,
furfural, and Purpureocillium lilacinum (=Paecilomyces lilacinus) strain 251.
Treatment applications were made during the spring and fall seasons according to
manufacturer's specifications. Efficacy was evaluated based on J2/100 cm3 of
soil, J2/g of root, and crop yield (kg/plot). Unlike spirotetramat, which did not
demonstrate any measurable effects on Meloidogyne incognita J2 in the soil,
furfural and P. lilacinum were marginally effective in reducing the population
density of M. incognita on Pittosporum tobira. However, nematode reduction did
not affect yield significantly. Although furfural and P. lilacinum have some
potential for management of M. incognita on cut foliage crops, their use as a
lone management option would likely not provide the needed level of control.
Early treatment application following infestation provided greater J2 suppression
compared to late application, suggesting the need for growers to avoid infested
fields.
PMID- 28706313
TI - Methyl Bromide Alternatives for Control of Root-knot Nematode (Meloidogyne spp.)
in Tomato Production in Florida.
AB - The following work was initiated to determine the scope of application
methodology and fumigant combinations for increasing efficacy of 1,3
dichloropropene (1,3-D) and metam sodium for management of root-knot nematodes
(Meloidogyne spp.) in Florida. A series of five experiments were set up during
spring and fall seasons to evaluate the potential of different fumigants, alone
or in combination, in polyethylene film tomato production. The most promising
chemical alternatives to methyl bromide, in terms of root-knot nematode
management, were the combinations 1,3-D-chloropicrin, chloropicrin-proprietary
solvent ,and 1,3-D-metam sodium. Sprayed or injected metam sodium generally
provided only short-term nematode management and by harvest nematode infection
was not different from the nontreated control. Drip-applied metam sodium gave
good nematode management under high nematode pressure, but needs further
verification to establish (i) the importance of soil moisture and temperature on
treatment efficacy and (ii) whether similar management can be obtained with fewer
than three drip tubes. Broadcast applications of 1,3-D showed better efficacy as
compared to applications on a preformed raised bed. Fumigation did not increase
tomato yields in spring when root-knot nematode pressure was low, but during fall
all chemical treatments increased yields three to five-fold, as root-knot
nematode was a major yield-limiting factor.
PMID- 28706314
TI - Sampling Error in Relation to Cyst Nematode Population Density Estimation in
Small Field Plots.
AB - Cyst nematodes are serious plant-parasitic pests which could cause severe yield
losses and extensive damage. Since there is still very little information about
error of population density estimation in small field plots, this study
contributes to the broad issue of population density assessment. It was shown
that there was no significant difference between cyst counts of five or seven
bulk samples taken per each 1-m2 plot, if average cyst count per examined plot
exceeds 75 cysts per 100 g of soil. Goodness of fit of data to probability
distribution tested with chi2 test confirmed a negative binomial distribution of
cyst counts for 21 out of 23 plots. The recommended measure of sampling precision
of 17% expressed through coefficient of variation (cv) was achieved if the plots
of 1 m2 contaminated with more than 90 cysts per 100 g of soil were sampled with
10-core bulk samples taken in five repetitions. If plots were contaminated with
less than 75 cysts per 100 g of soil, 10-core bulk samples taken in seven
repetitions gave cv higher than 23%. This study indicates that more attention
should be paid on estimation of sampling error in experimental field plots to
ensure more reliable estimation of population density of cyst nematodes.
PMID- 28706315
TI - Reproduction of Meloidogyne incognita and M. graminis on Several Grain Sorghum
Hybrids.
AB - A total of 27 grain sorghum hybrids were evaluated in a series of greenhouse
experiments to determine their susceptibility to Meloidogyne incognita race 3 and
M. graminis. Each hybrid was inoculated with 2,000 nematode eggs/pot.
Reproduction by M. incognita was numerically greater than M. graminis on 93% of
the hybrids tested, indicating that grain sorghum is a better host for M.
incognita than M. graminis. A wide variation in host suitability was observed on
these hybrids in a second experiment as reproduction by M. incognita ranged from
395 to 3,818 eggs/g of root. Only two hybrids, Terral RV9782 and RV9823,
consistently supported <20% reproduction by M. incognita compared to the most
susceptible hybrid, Golden Acres 5556. Reproduction of four isolates of M.
incognita was evaluated on six selected hybrids in a third greenhouse experiment.
Hybrid susceptibility was similar to that observed in the previous experiment for
all isolates. A difference in isolate aggressiveness was observed between two of
the four isolates across all hybrids. In fields where damaging populations of M.
incognita are present, most grain sorghum hybrids will likely maintain or
increase the nematode population for the subsequent crop.
PMID- 28706316
TI - Description of Pseudacrobeles (Pseudacrobeles) curvatus sp. n. (Cephalobidae:
Rhabditida) in South Korea.
AB - Pseudacrobeles (Pseudacrobeles) curvatus sp. n. was collected from potato fields
in Gyeongsangnam-do, South Korea. The new species shares morphological characters
typical of the genus Pseudacrobeles, including three lateral incisures that fade
posteriorly near the phasmid openings. The new species differs from other
Pseudacrobeles species by its smaller body size and a comparatively shorter
corpus relative to the isthmus length. In this study, we provide a comparison of
morphometrics and diagnostic features of Pseudacrobeles species and molecular
sequence data from the D2-D3 regions of the 28S ribosomal DNA (rDNA) and ITS1
5.8S-ITS2 region of rDNA from the new species, which can be used as molecular
barcode sequences.
PMID- 28706317
TI - Deladenus posteroporus n. sp. (Nematoda: Neotylenchidae) Isolated from Packaging
Wood from Canada and White Pine (Pinus monticola) Lumber from the United States
and Intercepted in Ningbo, China.
AB - : Deladenus posteroporus n. sp. isolated from packaging wood originated from
Canada and from white pine lumber from the United States, both intercepted in the
port of Ningbo, China, is described and illustrated. Both mycetophagous and
infective forms were recovered from the Canadian sample, whereas only the
mycetophagous form was found in the U.S. SAMPLE: The new species is characterized
by the posteriorly positioned excretory pore relative to the hemizonid in both
mycetophagous and infective forms, by a broadly rounded tail end in mycetophagous
females and lateral fields with 11 to 12 lines midbody in both mycetophagous
females and males. The partial 18S, complete internal transcribed spacer, and
partial 28S D2/D3 rRNA genes were amplified and sequenced. Phylogenetic analyses
of the genes grouped the new species with previously sequenced species of
Deladenus in a fully supported clade. This is the first report of Deladenus
species with a known infective stage to have the excretory pore positioned
posterior to the hemizonid.
PMID- 28706318
TI - Diversity of Root-knot Nematodes Associated with Tubers of Yam (Dioscorea spp.)
Established Using Isozyme Analysis and Mitochondrial DNA-based Identification.
AB - The root-knot nematodes (RKN), Meloidogyne spp., represent an important threat to
yam (Dioscorea spp.) production in West Africa. With the aim to establish the
diversity of RKN species affecting yam tubers, for control and resistance
screening purposes, surveys were conducted in the main yam producing areas of
Nigeria. Galled tubers (N = 48) were collected from farmers' stores and markets
in nine states in Nigeria and in one district in Ghana. RKN isolated from yam
tubers were identified using enzyme phenotyping (esterase and malate
dehydrogenase) and mitochondrial DNA (mtDNA) NADH dehydrogenase subunit 5 (Nad5)
barcoding. Examination of 48 populations revealed that yam tubers were infested
by Meloidogyne incognita (69%), followed by M. javanica (13%), M. enterolobii
(2%), and M. arenaria (2%). Most of the tubers sampled (86%) were infected by a
single species, and multiple species of RKN were detected in 14% of the samples.
Results of both identification methods revealed the same species, confirming
their accuracy for the identification of these tropical RKN species. In addition
to M. incognita, M. javanica, and M. enterolobii, we report for the first time M.
arenaria infecting yam tubers in Nigeria. This finding extends the list of yam
pests and calls for caution when developing practices for yam pest management.
PMID- 28706319
TI - Redefinition of Genus Malenchus Andrassy, 1968 (Tylenchomorpha: Tylenchidae) with
Additional Data on Ecology.
AB - Malenchus is the second specious genus in Tylenchidae. In the presented study, we
examined 22 populations including 12 type/paratype species. Detailed morphology
was recovered using light microscopy, scanning- and transmission- electron
microscopy. All population and type slides were recorded as picture and video
vouchers, which are available online. We have compared inter- or intraspecific
variations and extracted taxonomically informative traits. Amended definitions of
the Malenchus as well as the closely related Ottolenchus were given based on a
combination of morphology and recent molecular data, and their phylogeny were
analyzed in a context of Tylenchidae. Furthermore, we test different fungi and
moss as a food resource of Malenchus and their feeding behavior is also
discussed.
PMID- 28706320
TI - Numerical Taxonomy Helps Identification of Merliniidae and Telotylenchidae
(Nematoda: Tylenchoidea) from Iran.
AB - Numerical taxonomy was used for identification and grouping of the genera,
species, and populations in the families Merliniidae and Telotylenchidae. The
variability of each of 44 morphometric characters was evaluated by calculation of
the coefficient of variability (CV) and the ratio of extremes (max/min) in the
range of 1,020 measured females. Also correlation and regression analyses were
made between characters to find potential collinearities. Hierarchical cluster
analysis (HCA) was used for (i) grouping 21 genera in the superfamily
Dolichodoroidea based on literature data coded for states of 18 diagnostic
characters, and (ii) for grouping Iranian populations belonging to selected
genera. Furthermore, STEPDISC analysis was used for (i) grouping 11 genera of
Merliniidae and Telotylenchidae based on the measurements of 35 characters from
1,007 Iranian female specimens, and (ii) grouping measured females of eight
species of Amplimerlinius and Pratylenchoides. The multivariate data analysis
approach showed robust enough to summarize relationship between morphometric
characters and group genera, species, and populations of the nematodes and in
particular help to identify the genera and species of Amplimerlinius and
Pratylenchoides.
PMID- 28706321
TI - Cryptaphelenchus varicaudatus n. sp. (Rhabditida: Ektaphelenchinae) from Tehran
Province, Iran.
AB - Cryptaphelenchus varicaudatus n. sp. is described and illustrated. It was
isolated from bark samples of dead or dying pine (Pinus spp.) trees with bark
beetle frass and galleries, in Tehran province. The new species has 275- to 367
um-long females (a medium-sized species) with distinctly annulated cuticle having
three bands in lateral fields, lip region continuous with body contour, delicate
knobbed stylet, monodelphic-prodelphic reproductive system with distinct
spermatheca, short postvulval uterine sac (PUS), transverse vulval slit with
raised posterior lip and body narrowing behind it, sclerotized vagina, simple
intestine ending in a blind sac, having no rectum but vestigial anus in some
specimens, and distal body end tip (tail tip) with variation in morphology
(shape), from sharply or slightly pointed to bluntly rounded. Males of the new
species are common, but less frequent than females, characterized by shorter body
(235-278 um long) compared to females, their posterior body end more ventrally
bent, arcuate separate spicules with well-developed wide condyles, distinct
rostrum having sharp, attenuated tip. The precloacal single supplement (P1) and
the distally located pair of caudal papillae close to tail tip were only
observed. The new species is morphologically compared with the species of the
genus having short PUS and similar body end morphology. In molecular phylogenetic
analyses using 1520- and 698-nt-long sequences of small subunit (SSU) and large
subunit (LSU) rDNA D2/D3 fragments, the new species formed a clade with two
currently available GenBank-derived, unspecified isolates/sequences in SSU and
three other isolates/sequences in LSU trees, respectively.
PMID- 28706322
TI - Respirable dust measured downwind during rock dust application.
AB - The Pittsburgh Mining Research Division of the U.S. National Institute for
Occupational Safety and Health (NIOSH) conducted underground evaluations in an
attempt to quantify respirable rock dust generation when using untreated rock
dust and rock dust treated with an anticaking additive. Using personal dust
monitors, these evaluations measured respirable rock dust levels arising from a
flinger-type application of rock dust on rib and roof surfaces. Rock dust with a
majority of the respirable component removed was also applied in NIOSH's Bruceton
Experimental Mine using a bantam duster. The respirable dust measurements
obtained downwind from both of these tests are presented and discussed. This
testing did not measure miners' exposure to respirable coal mine dust under
acceptable mining practices, but indicates the need for effective continuous
administrative controls to be exercised when rock dusting to minimize the
measured amount of rock dust in the sampling device.
PMID- 28706323
TI - Exploring the existence of a stayer population with mover-stayer counting process
models: application to joint damage in psoriatic arthritis.
AB - Many psoriatic arthritis patients do not progress to permanent joint damage in
any of the 28 hand joints, even under prolonged follow-up. This has led several
researchers to fit models that estimate the proportion of stayers (those who do
not have the propensity to experience the event of interest) and to characterize
the rate of developing damaged joints in the movers (those who have the
propensity to experience the event of interest). However, when fitted to the same
data, the paper demonstrates that the choice of model for the movers can lead to
widely varying conclusions on a stayer population, thus implying that, if
interest lies in a stayer population, a single analysis should not generally be
adopted. The aim of the paper is to provide greater understanding regarding
estimation of a stayer population by comparing the inferences, performance and
features of multiple fitted models to real and simulated data sets. The models
for the movers are based on Poisson processes with patient level random effects
and/or dynamic covariates, which are used to induce within-patient correlation,
and observation level random effects are used to account for time varying
unobserved heterogeneity. The gamma, inverse Gaussian and compound Poisson
distributions are considered for the random effects.
PMID- 28706324
TI - Didymellaceae revisited.
AB - The Didymellaceae is one of the most species-rich families in the fungal kingdom,
and includes species that inhabit a wide range of ecosystems. The taxonomy of
Didymellaceae has recently been revised on the basis of multi-locus DNA sequence
data. In the present study, we investigated 108 Didymellaceae isolates newly
obtained from 40 host plant species in 27 plant families, and various substrates
from caves, including air, water and carbonatite, originating from Argentina,
Australia, Canada, China, Hungary, Israel, Italy, Japan, South Africa, the
Netherlands, the USA and former Yugoslavia. Among these, 68 isolates representing
32 new taxa are recognised based on the multi-locus phylogeny using sequences of
LSU, ITS, rpb2 and tub2, and morphological differences. Within the Didymellaceae,
five genera appeared to be limited to specific host families, with other genera
having broader host ranges. In total 19 genera are recognised in the family, with
Heracleicola being reduced to synonymy under Ascochyta. This study has
significantly improved our understanding on the distribution and biodiversity of
Didymellaceae, although the placement of several genera still need to be
clarified.
PMID- 28706326
TI - Changing trends in pharmacology....
PMID- 28706325
TI - AXSIS: Exploring the frontiers in attosecond X-ray science, imaging and
spectroscopy.
AB - X-ray crystallography is one of the main methods to determine atomic-resolution
3D images of the whole spectrum of molecules ranging from small inorganic
clusters to large protein complexes consisting of hundred-thousands of atoms that
constitute the macromolecular machinery of life. Life is not static, and
unravelling the structure and dynamics of the most important reactions in
chemistry and biology is essential to uncover their mechanism. Many of these
reactions, including photosynthesis which drives our biosphere, are light induced
and occur on ultrafast timescales. These have been studied with high time
resolution primarily by optical spectroscopy, enabled by ultrafast laser
technology, but they reduce the vast complexity of the process to a few reaction
coordinates. In the AXSIS project at CFEL in Hamburg, funded by the European
Research Council, we develop the new method of attosecond serial X-ray
crystallography and spectroscopy, to give a full description of ultrafast
processes atomically resolved in real space and on the electronic energy
landscape, from co-measurement of X-ray and optical spectra, and X-ray
diffraction. This technique will revolutionize our understanding of structure and
function at the atomic and molecular level and thereby unravel fundamental
processes in chemistry and biology like energy conversion processes. For that
purpose, we develop a compact, fully coherent, THz-driven atto-second X-ray
source based on coherent inverse Compton scattering off a free-electron crystal,
to outrun radiation damage effects due to the necessary high X-ray irradiance
required to acquire diffraction signals. This highly synergistic project starts
from a completely clean slate rather than conforming to the specifications of a
large free-electron laser (FEL) user facility, to optimize the entire
instrumentation towards fundamental measurements of the mechanism of light
absorption and excitation energy transfer. A multidisciplinary team formed by
laser-, accelerator,- X-ray scientists as well as spectroscopists and biochemists
optimizes X-ray pulse parameters, in tandem with sample delivery, crystal size,
and advanced X-ray detectors. Ultimately, the new capability, attosecond serial X
ray crystallography and spectroscopy, will be applied to one of the most
important problems in structural biology, which is to elucidate the dynamics of
light reactions, electron transfer and protein structure in photosynthesis.
PMID- 28706327
TI - Current advances in transdermal delivery of drugs for Alzheimer's disease.
AB - Alzheimer's disease (AD) is a common, progressive, fatal neurodegenerative
disorder, which will play an increasingly important role both socially and
financially in the aging populations. Treatments for AD show modest improvements
in cognition and global functioning among patients. Furthermore, the oral
administration of treating AD has had some drawbacks that decrease the medication
adherence and efficacy of the therapy. Transdermal drugs are proposed as an
alternative remedy to overcome the disadvantages of current pharmaceutical dosage
options for this chronic disorder. They could have different strengths, such as
offering a stable diffusion of active substance, avoiding the first pass
metabolism, and reducing system adverse reactions. This article reviews the
technical principles, novel techniques of transdermal delivery drug, and
prospects for future development for the management of cognitive and behavioral
dysfunctions in AD patients.
PMID- 28706328
TI - Trypsin inhibitors demonstrate antioxidant activities, inhibit A549 cell
proliferation, and increase activities of reactive oxygen species scavenging
enzymes.
AB - OBJECTIVES: Protease inhibitors are one of the most promising and investigated
subjects for their role in pharmacognostical and pharmacological studies. This
study aimed to investigate antineoplastic and antioxidant activity of trypsin
inhibitors (TIs) isolated from three plant sources and their inhibitory role in
the cell line. MATERIALS AND METHODOLOGY: TIs were obtained from different plant
sources. Antineoplastic potential on adenocarcinoma human alveolar basal
epithelial cell line (A549) and normal Human Embryonic Kidney (HEK) was
determined using MTT assay. Activities of antioxidant enzyme, nitric oxide
scavenger, superoxide dismutase, glutathione S-transferase, and glutathione
peroxidase were assessed in cell lines incubated with and without TIs. The
outcome was analyzed by spectrophotometer. RESULTS: TIs showed the higher
cytotoxicity on A549 cells as compared to normal HEK cell line. TIs exhibited
fair increase in antioxidant enzyme activity in A549 cells as compared to
control. This might be one of the strategies of antineoplastic effect in cancer
cells. CONCLUSIONS: This study has reported the antioxidant and antineoplastic
properties of these TIs for the first time in A549 cells (to the best of our
knowledge). The results show that TIs possess ability to prevent cancer and
diseases caused due to oxidative stress. Therefore, we conclude that TIs can be
used as supplements along with the conventional drugs for increased efficacy in
the treatment of diseases such as cardiovascular disease, atherosclerosis, and
cancer.
PMID- 28706329
TI - Effect of karanjin on 2,4,6-trinitrobenzenesulfonic acid-induced colitis in
Balb/c mice.
AB - OBJECTIVES: The objective of this study is to evaluate the beneficial effect of
karanjin for the treatment of experimental colitis. METHODS: Colitis was induced
in the Balb/c mice by rectal administration of 2% solution of 2,4,6
trinitrobenzenesulfonic acid (TNBS) in 50% methanol. Karanjin (>98% pure) was
administered in two different concentrations 100 and 200 mg/kg and sulfasalazine
(100 mg/kg) as reference for 7 consecutive days to colitic mice. On the 8 day,
mice were euthanized and degree of inflammation was assessed by macroscopic,
microscopic, histology and biochemical estimation of myeloperoxidase (MPO),
nitric oxide (NO), malondialdehyde (MDA), catalase (CAT), superoxide dismutase
(SOD), and reduced glutathione (GSH) level were measured. RESULTS: Karanjin
significantly and dose dependently ameliorate the macroscopic damage,
histological changes such as cellular infiltration, tissue necrosis, mucosal and
submucosal damage as compared to the TNBS control group. Karanjin reduces the
activity of MPO, depressed MDA, and NO level and helps in restoring the level of
CAT, SOD, and GSH to normal when compared to the TNBS colitis group. CONCLUSION:
Result of the present study indicates that karanjin has the potential to cure
colitis induced by intracolonic administration of TNBS.
PMID- 28706330
TI - Effects of co-treatment with pioglitazone and methotrexate on experimentally
induced rheumatoid arthritis in Wistar albino rats.
AB - OBJECTIVES: Rheumatoid arthritis (RA) is a chronic inflammatory disease primarily
affecting the synovial joints of the body. Methotrexate (MTX) is considered as a
mainstay in the management of RA. However, monotherapy with MTX in RA is often
limited by potential long-term toxicity. The present study was conducted to
evaluate if MTX-pioglitazone combination therapy has an add-on benefit over
monotherapy with MTX or pioglitazone on disease activity in male Wistar rats in
adjuvant-induced arthritis model. MATERIALS AND METHODS: Arthritis was induced by
single subcutaneous injection of complete Freund's adjuvant (CFA) in thirty male
Wistar albino rats. They were then divided into five equal groups, which included
two control groups (arthritic and nonarthritic), pioglitazone-treated (1.35 mg/kg
daily), MTX-treated (0.225 mg/kg daily), and MTX + pioglitazone-treated. The
disease-modifying action of the drugs was assessed by various physiological,
hematological, and biochemical parameters along with histopathological and
radiological analysis of affected joints. The experimental data were
statistically assessed by one-way ANOVA. RESULTS: There was a significant
reduction of disease activity in the MTX monotherapy group when compared with
disease control. However, pioglitazone monotherapy group failed to demonstrate
any significant effect on disease activity. The MTX-pioglitazone combination
group demonstrated greater suppression of disease activity as compared to MTX and
pioglitazone monotherapy and disease control group (P < 0.05). CONCLUSION: The
present study demonstrates that the combination therapy of MTX with pioglitazone
offers better control of disease activities in RA as compared to MTX or
pioglitazone monotherapy.
PMID- 28706331
TI - Bioequivalence of generic and branded amoxicillin capsules in healthy human
volunteers.
AB - CONTEXT: The Medical Council of India urges doctors to prescribe generic drugs as
far as possible. The Indian Medical Association had responded earlier saying that
it requires guarantees on the quality of generic forms of drugs. Although no
published scientific reports are available on the issue of therapeutic
inequivalence, unconfirmed clinician accounts and newspaper reports of
therapeutic inequivalence exist. AIM: This study was planned to ascertain whether
bioequivalence of branded and generic amoxicillin capsule is comparable. SETTINGS
AND DESIGN: An open-label, randomized, single-dose, two-treatment, two-sequence,
two-period crossover oral bioequivalence study was conducted in 12 healthy, adult
human subjects under fasting condition. MATERIALS AND METHODS: Serum samples,
collected at 8 time points, were analyzed by a validated ultraviolet
spectrophotometer method. Pharmacokinetic (PK) parameters such as area under the
curve (AUC)0-t, AUC0-infinity, Cmax, and Tmax were determined along with time
above minimum inhibitory concentration (MIC). STATISTICAL ANALYSIS USED: The log
transformed PK parameters (Cmax, AUC0-t, AUC0-infinity) were analyzed using a Two
One-Sided Test ANOVA in SAS for each parameter. Tmax and MIC were analyzed by
Wilcoxon rank-sum test in GraphPad Prism. RESULTS: Geometric mean ratio of Cmax
fell within bioequivalence criteria. The upper and lower confidence limits of
both AUC0-t and AUC0-infinity geometric mean ratio fell below bioequivalence
criteria. Time above MIC of generic preparation was significantly lower than that
of branded version. CONCLUSIONS: The generic capsule was not bioequivalent to the
branded amoxicillin capsule.
PMID- 28706332
TI - Role of Elsholtzia communis in counteracting stress by modulating expression of
hspa14, C/EBP homologous protein, nuclear factor (erythroid-derived 2)-like-2
factor, Caspase-3, and brain-derived neurotrophic factor in rat hippocampus.
AB - OBJECTIVE: Elsholtzia communis (Collett and Hemsl.) Diels has been widely
distributed and is reported for many therapeutic effects. The present study aims
to investigate the antistress activity of the leaf extract and its possible
molecular mechanism. MATERIALS AND METHODS: Hydroethanolic extract of leaves of
E. communis (100 and 200 mg/kg, p.o.) were administered for 7 days to stress
induced male Wistar rats. The experimental animals were divided into five groups
(n = 6). The mRNA/protein profile of few stress responsive chaperones (hspa14),
endoplasmic reticulum stress markers (C/EBP homologous protein [CHOP]),
antioxidant regulating genes (nuclear factor (erythroid-derived 2)-like-2 factor
[Nrf2]), apoptotic factors (Caspase-3) in rat hippocampus were studied by
polymerase chain reaction and immunoblotting. RESULTS: The stress-related genes
such as hspa14, CHOP, antioxidant gene Nrf2, apoptotic gene Caspase-3 which were
overexpressed in the stress control group were significantly suppressed following
administration of the extract at both the doses and the standard drug Ginseng.
Likewise, brain-derived neurotrophic factor which is closely related with stress,
was downregulated in the stress control group, was found to be upregulated
following treatment with the extract and the standard drug Ginseng. CONCLUSION:
Our findings clearly indicate that E. communis was able to counteract stress.
Hence, it has the potential to develop as adaptogen and also as a
replacement/substitute of the popularly used drug, Ginseng or Ashwagandha, which
is on the verge of extinction or becoming endemic due to overuse.
PMID- 28706333
TI - Availability of pediatric-evaluated formulations in Serbia.
AB - OBJECTIVES: The aim of this study is to analyze the availability and coverage by
health insurance reimbursement of pediatric formulations labeled for children up
to the age of 12 in Serbia. To provide good insight in general availability of
pediatric medicines, results were compared with the World Health Organization's
(WHO) "Model List of Essential Medicines for Children" and with published
evidence. MATERIALS AND METHODS: Sources of information about medicines are the
Summary of Product Characteristics, National Health Insurance Fund (NHIF) Drug
Lists, WHO Model Lists of Essential Medicines for Children, and Serbia's official
drug registry (2013). RESULTS: Out of total number of medicines in Serbia, only
49% (496) were available for children. Of all available drugs for children, 66%
were with license and majority were parenteral formulation (57%), followed by
drugs for local use (28%) and formulations for oral use (23%). The lowest
availability of medicines was for children 0-27 days. From the total number of
licensed medicines for children up to 12 years old, NHIF covers 64% of drugs. The
availability of the WHO essential medicines for children in Serbia was 51%, from
which 92% were licensed for pediatric use. CONCLUSIONS: Our results demonstrated
the alarming lack of pediatric suitable formulations in Serbia. Significant
differences in the availability of drugs suitable for children exist worldwide.
From global health point of view, the differences in the access to children
formulations should, therefore, be of the highest priority.
PMID- 28706334
TI - An evaluation of impact of educational interventions on the technique of use of
metered-dose inhaler by patients.
AB - OBJECTIVES: The objective of this study is to evaluate the impact of two
educational interventions that are demonstration versus pictorial Leaflet in
patients using metered-dose inhaler (MDI). MATERIALS AND METHODS: This
interventional study was done in patients who were prescribed drugs through MDI
at Tuberculosis and Chest Department. The patients were enrolled in Group A or
Group B as per random number table method. The method of use of MDI was assessed
using a checklist based on the technique described in the WHO Guide to good
prescribing. Patients in Group A were taught the use of MDI by demonstration of
the technique by the investigator. Patients in Group B were educated about the
technique by a pictorial leaflet based on the technique. Patients were followed
up after 15 days and assessed for correct technique for use of the MDI. RESULTS:
A total 100 patients were included in the study and were allotted to Group A (47)
and Group B (53). Ninety-five percent of the patients had been taught by the
treating physician about the method of use of MDI. All the patients at the
baseline placed the lips tightly around the mouthpiece and held the aerosol as
indicated in the manufacturer's instructions while the step least followed was
coughing up the sputum before inhalation. The average steps correctly followed by
the patients in Group A and B at baseline were 5.17 +/- 2.07 and 5.11 +/- 2.04,
respectively. These improved significantly to 9.19 +/- 0.67 and 6.67 +/- 0.63 in
Group A and B, respectively, postintervention. The five essential steps of using
MDI were followed by 25.53% and 26.41% patients preintervention. An improvement
in the technique of use of MDI was observed in 85.11% and 49.06% patients (P =
0.003) postintervention. All the ten steps of the technique were followed by
34.04% patients from Group A and none from Group B at postintervention evaluation
(P = 0.0001). CONCLUSION: The inhalation technique for the use of MDI used by the
patients is inappropriate. Educational interventions such as demonstration or
pictorial leaflet help ensure a better use of the MDI.
PMID- 28706335
TI - Prevalence of statin use among high-risk patients in urban and rural Vellore,
Tamil Nadu: A population-based cross-sectional study.
AB - OBJECTIVES: This study assessed statin use among diabetics and those with
coronary heart disease (CHD) in Vellore, Tamil Nadu. METHODS: A cross-sectional
survey was conducted in rural and urban Vellore, among 6196 participants (30-64
years), in 2010-2012. Statin use among those with known CHD and diabetes (on
diabetic medication) was recorded. A randomly selected sample of rural diabetics
was resurveyed in 2016 to reassess statin use. RESULTS: Among 61 with CHD, 23
(37.7%) were on statins. Statin use among 422 diabetics aged >=40 years with low
density lipoprotein >=70 mg/dl was 13.4% in urban and 7.6% among rural. Statin
usage among rural diabetics aged >=40 years increased from 7.7% in 2010-2012 to
16.6% in 2016. CONCLUSIONS: Statin use for CHD was below 50% although higher than
the use among diabetics, indicating the need to address this low rate of usage
among these high-risk groups.
PMID- 28706336
TI - Palmoplantar exfoliation due to chloroquine.
AB - Chloroquine is the drug very frequently used for the treatment of malaria. It is
also used in amebiasis, rheumatoid arthritis, and various dermatological
conditions. Chloroquine can cause muscle problems, loss of appetite, and diarrhea
as a side effect. Cutaneous toxicity includes pruritus, hair loss,
photosensitivity, and color changes. Exfoliation of skin over palms and soles is
caused by chemotherapeutic drugs such as axitinib, fluorouracil, idarubicin,
doxorubicin, sunitinib, sorafenib, and paclitaxel. Here, a case of a 40-year-old
female is presented who developed palmoplantar exfoliation with depigmentation
after taking chloroquine. Although not life-threatening, this side effect of a
commonly used drug may cause anxiety and functional impairment which in turn
affects the quality of life of an individual.
PMID- 28706337
TI - Antibiotic resistance: Alternative approaches.
PMID- 28706338
TI - Erratum: Evaluation of cytochrome P450 2C9 activity in normal, healthy, adult
Western Indian population by both phenotyping and genotyping.
AB - [This corrects the article on p. 248 in vol. 48, PMID: 27298492.].
PMID- 28706339
TI - Expansion of bone marrow-derived human mesenchymal stem/stromal cells (hMSCs)
using a two-phase liquid/liquid system.
AB - BACKGROUND: Human mesenchymal stem/stromal cells (hMSCs) are at the forefront of
regenerative medicine applications due to their relatively easy isolation and
availability in adults, potential to differentiate and to secrete a range of
trophic factors that could determine specialised tissue regeneration. To date,
hMSCs have been successfully cultured in vitro on substrates such as polystyrene
dishes (TCPS) or microcarriers. However, hMSC sub-cultivation and harvest
typically employs proteolytic enzymes that act by cleaving important cell
membrane proteins resulting in long-term cell damage. In a process where the
cells themselves are the product, a non-enzymatic and non-damaging harvesting
approach is desirable. RESULTS: An alternative system for hMSC expansion and
subsequent non-enzymatic harvest was investigated here. A liquid/liquid two-phase
system was proposed, comprising a selected perfluorocarbon (FC40) and growth
medium (DMEM). The cells exhibited similar cell morphologies compared with TCPS.
Moreover, they retained their identity and differentiation potential post
expansion and post-harvest. Further, no significant difference was found when
culturing hMSCs in the culture systems prepared with either fresh or recycled
FC40 perfluorocarbon. CONCLUSIONS: These findings make the FC40/DMEM system an
attractive alternative for traditional cell culture substrates due to their ease
of cell recovery and recyclability, the latter impacting on overall process
costs. (c) 2017 The Authors. Journal of Chemical Technology & Biotechnology
published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
PMID- 28706340
TI - Transport phenomena governing nicotine emissions from electronic cigarettes:
model formulation and experimental investigation.
AB - Electronic cigarettes (ECIGs) electrically heat and aerosolize a liquid
containing propylene glycol (PG), vegetable glycerin (VG), flavorants, water, and
nicotine. ECIG effects and proposed methods to regulate them are controversial.
One regulatory focal point involves nicotine emissions. We describe a
mathematical model that predicts ECIG nicotine emissions. The model computes the
vaporization rate of individual species by numerically solving the unsteady
species and energy conservation equations. To validate model predictions, yields
of nicotine, total particulate matter, PG, and VG were measured while
manipulating puff topography, electrical power, and liquid composition across 100
conditions. Nicotine flux, the rate at which nicotine is emitted per unit time,
was the primary outcome. Across conditions, the measured and computed nicotine
flux were highly correlated (r = 0.85, p<.0001). As predicted, device power,
nicotine concentration, PG/VG ratio, and puff duration influenced nicotine flux
(p<.05), while water content and puff velocity did not. Additional empirical
investigation revealed that PG/VG liquids act as ideal solutions, that liquid
vaporization accounts for more than 95% of ECIG aerosol mass emissions, and that
as device power increases the aerosol composition shifts towards the less
volatile components of the parent liquid. To the extent that ECIG regulations
focus on nicotine emissions, mathematical models like this one can be used to
predict ECIG nicotine emissions and to test the effects of proposed regulation of
factors that influence nicotine flux.
PMID- 28706341
TI - Conflict over non-partitioned resources may explain between-species differences
in declines: the anthropogenic competition hypothesis.
AB - ABSTRACT: Human alterations of habitats are causing declines in many species
worldwide. The extent of declines varies greatly among closely related species,
for often unknown reasons that must be understood in order to maintain
biodiversity. An overlooked factor is that seasonally breeding species compete
for nest sites, which are increasingly limited in many anthropogenically degraded
environments. I used evolutionary game theory to predict the outcome of
competition between individuals that differ in their competitive ability and
timing of nesting. A range of species following evolutionarily stable strategies
can co-exist when there are sufficient nest sites, but my model predicts that a
reduction in nest site availability has greater impacts on late-nesting species,
especially the stronger competitors, whereas early-nesting, stronger species
decline only slightly. These predictions are supported by data on 221 bird and 43
bumblebee species worldwide. Restoration and provision of nest sites should be an
urgent priority in conservation efforts. More broadly, these results indicate a
new ecological principle of potentially widespread importance: rapid reductions
in the abundance of resources for which species' preferences have not diversified
will result in unprecedented conflicts that reduce the potential for species co
existence. SIGNIFICANCE STATEMENT: Understanding the causes of species declines
is crucial to preventing the losses. Whilst much work on species vulnerability
shows broad scale effects, an enduring mystery is the variation in population
trends between closely related species. I combined evolutionary modelling with
three global-scale long-term data sets to reveal that competition for scarce nest
sites causes variation in declines. The impact of the loss of nest sites on
differential declines among closely related species from very different taxa
indicates a new ecological principle of widespread importance: the effect of
habitat degradation on competition among species. A lack of differentiation of
nest site preferences means that-now nest sites are more limited-some species may
be driving others to extinction. This phenomenon is likely to occur for any other
non-partitioned resources that rapidly, on an evolutionary timescale, are now
limiting population sizes.
PMID- 28706342
TI - Punish the thief-coevolution of defense and cautiousness stabilizes ownership.
AB - ABSTRACT: Ownership of non-controllable resources usually has to be maintained by
costly defense against competitors. Whether defense and thus ownership pays in
terms of fitness depends on its effectiveness in preventing theft. We show that
if the owners' willingness to defend varies in the population and information
about it is available to potential thieves then the ability to react to this
information and thus avoid being attacked by the owner is selected for. This can
lead to a positive evolutionary feedback between cautiousness in intruders and
aggressiveness in owners. This feedback can maintain ownership when the actual
direct effectiveness of defense in reducing theft is very low or even absent,
effectively turning defense into punishment. We conclude that the deterrence
effect of defense in many situations could be stronger than that of prevention
and that for many real-world scenarios the purpose of defense of resources might
be to punish rather than to drive away intruders. SIGNIFICANCE STATEMENT: Many
animals defend resources against conspecifics. Resource defense can usually only
evolve if its costs are paid for by foiling attempts at theft. We show that if
potential thieves can detect differences in aggressiveness between owners then
cautious intruders and aggressive owners coevolve so that in the end even
ineffective defense deters thieves and maintains ownership. This result greatly
extends the number of situations in which we expect resource defense to evolve
and has the potential to unify the concepts of defense and punishment.
PMID- 28706343
TI - New thermoplastic poly(carbonate-urethane)s based on chain extenders with sulfur
atoms.
AB - New thermoplastic segmented polyurethanes were obtained by a one-step melt
polyaddition using 40, 50 and 60 mol% poly(hexane-1,6-diyl carbonate) diol of
[Formula: see text] g mol-1, 1,1'-methanediylbis(4-isocyanatobenzene) and 2,2'
[sulfanediylbis(benzene-1,4-diyloxy)]diethanol, 2,2'-[oxybis(benzene-1,4
diylsulfanediyl)]diethanol or 2,2'-[sulfanediylbis(benzene-1,4
diylsulfanediyl)]diethanol as a chain extender. FTIR, atomic force microscopy,
differential scanning calorimetry and thermogravimetry were used to examine the
polyurethanes' structure and thermal properties. Moreover, their Shore A/D
hardness, tensile, adhesive and optical attributes were determined. They were
transparent high-molar-mass materials showing good tensile strength (up to 51.9
MPa). The polyurethanes exhibited improved adhesion to copper taking into
consideration that of conventional ones, and middle or high refractive index
values (1.57-1.60), and both these parameters increased with an increase of the
content of sulfur atoms in the polyurethane chain. The newly obtained
polyurethanes can be considered as materials for numerous medical and optical
appliances.
PMID- 28706344
TI - A new model of cavern diameter based on a validated CFD study on stirring of a
highly shear-thinning fluid.
AB - Results of numerical simulations of momentum transfer for a highly shear-thinning
fluid (0.2% Carbopol) in a stirred tank equipped with a Prochem Maxflo T type
impeller are presented. The simulation results were validated using LDA data and
both tangential and axial force measurements in the laminar and early
transitional flow range. A good agreement between the predicted and experimental
results of the local fluid velocity components was found. From the predicted and
experimental values of both tangential and axial forces, the power number, Po,
and thrust number, Th, were also calculated. Values of the absolute relative
deviations were below 4.0 and 10.5%, respectively, for Po and Th, which confirms
a satisfactory agreement with experiments. An intensive mixing zone, known as
cavern, was observed near the impeller. In this zone, the local values of fluid
velocity, strain rate, Metzner-Otto coefficient, shear stress and intensity of
energy dissipation were all characterized by strong variability. Based on the
results of experimental study a new model using non-dimensional impeller force
number was proposed to predict the cavern diameter. Comparative numerical
simulations were also carried out for a Newtonian fluid (water) and their results
were similarly well verified using LDA measurements, as well as experimental
power number values.
PMID- 28706345
TI - A FISCHER INDOLIZATION STRATEGY TOWARD THE TOTAL SYNTHESIS OF (-)-GONIOMITINE.
AB - A Fischer indolization strategy toward the core of (-)-goniomitine is reported.
Initial investigations into the Pd-catalyzed asymmetric allylic alkylation of
dihydropyrido[1,2-a]indolone (DHPI) substrates are also discussed.
PMID- 28706346
TI - Individual Differences in the Resistance to Social Change and Acceptance of
Inequality Predict System Legitimacy Differently Depending on the Social
Structure.
AB - We propose that individual differences in the resistance to social change and the
acceptance of inequality can have divergent effects on legitimacy depending on
the context. This possibility was tested in a sample of 27 European countries (N
= 144 367) and across four experiments (total N = 475). Individual differences in
the resistance to social change were related to higher levels of perceived
legitimacy no matter the level of inequality of the society. Conversely,
individual differences in the acceptance of inequality were related to higher
levels of perceived legitimacy in unequal societies, but either a relationship
near zero or the opposite relationship was found in more equal societies. These
studies highlight the importance of distinguishing between individual differences
that make up political ideology, especially when making predictions in diverse
settings. (c) 2017 The Authors. European Journal of Personality published by John
Wiley & Sons Ltd on behalf of European Association of Personality Psychology.
PMID- 28706347
TI - Ga for Zn Cation Exchange Allows for Highly Luminescent and Photostable InZnP
Based Quantum Dots.
AB - In this work, we demonstrate that a preferential Ga-for-Zn cation exchange is
responsible for the increase in photoluminescence that is observed when gallium
oleate is added to InZnP alloy QDs. By exposing InZnP QDs with varying Zn/In
ratios to gallium oleate and monitoring their optical properties, composition,
and size, we conclude that Ga3+ preferentially replaces Zn2+, leading to the
formation of InZnP/InGaP core/graded-shell QDs. This cation exchange reaction
results in a large increase of the QD photoluminescence, but only for InZnP QDs
with Zn/In >= 0.5. For InP QDs that do not contain zinc, Ga is most likely
incorporated only on the quantum dot surface, and a PL enhancement is not
observed. After further growth of a GaP shell and a lattice-matched ZnSeS outer
shell, the cation-exchanged InZnP/InGaP QDs continue to exhibit superior PL QY
(over 70%) and stability under long-term illumination (840 h, 5 weeks) compared
to InZnP cores with the same shells. These results provide important mechanistic
insights into recent improvements in InP-based QDs for luminescent applications.
PMID- 28706348
TI - A methodological approach to the study of archaeological cereal meals: a case
study at Catalhoyuk East (Turkey).
AB - This paper presents an integrated methodology for the analysis of archaeological
remains of cereal meals, based on scanning electronic microscopic analyses of
microstructures of charred food fragments from Neolithic Catalhoyuk (Turkey). The
remains of cereal foods as 'bread-like' or 'porridge-like' small charred lumps of
various amalgamated plant materials are frequently recovered from Neolithic and
later archaeological sites in southwest Asia and Europe. Cereal food remains have
recently attracted interest because the identification of their plant contents,
the forms of food that they represent and the methods used in their creation can
provide unique information about ancient culinary traditions and routine food
processing, preparation and cooking techniques. Here, we focus on three
methodological aspects: (1) the analysis of their composition; (2) the analysis
of their microstructure to determine preparation and cooking processes; (3) the
comparison with experimental reference materials. Preliminary results are
presented on the botanical composition and cooking processes represented by the
charred cereal preparations found at Neolithic Catalhoyuk (Turkey), for example
cereals processed into bread, dough and/or porridge.
PMID- 28706349
TI - Training echo state networks for rotation-invariant bone marrow cell
classification.
AB - The main principle of diagnostic pathology is the reliable interpretation of
individual cells in context of the tissue architecture. Especially a confident
examination of bone marrow specimen is dependent on a valid classification of
myeloid cells. In this work, we propose a novel rotation-invariant learning
scheme for multi-class echo state networks (ESNs), which achieves very high
performance in automated bone marrow cell classification. Based on representing
static images as temporal sequence of rotations, we show how ESNs robustly
recognize cells of arbitrary rotations by taking advantage of their short-term
memory capacity. The performance of our approach is compared to a classification
random forest that learns rotation-invariance in a conventional way by
exhaustively training on multiple rotations of individual samples. The methods
were evaluated on a human bone marrow image database consisting of granulopoietic
and erythropoietic cells in different maturation stages. Our ESN approach to cell
classification does not rely on segmentation of cells or manual feature
extraction and can therefore directly be applied to image data.
PMID- 28706350
TI - Investigating the Electronic Portal Imaging Device for Small Radiation Field
Measurements.
AB - PURPOSE: With the advent of state-of-the-art treatment technologies, the use of
small fields has increased, and dosimetry in small fields is highly challenging.
In this study, the potential use of Varian electronic portal imaging device
(EPID) for small field measurements was explored for 6 and 15 MV photon beams.
MATERIALS AND METHODS: The output factors and profiles were measured for a range
of jaw-collimated square field sizes starting from 0.8 cm * 0.8 cm to 10 cm * 10
cm using EPID. For evaluation purpose, reference data were acquired using Exradin
A16 microionization chamber (0.007 cc) for output factors and stereotactic field
diode for profile measurements in a radiation field analyzer. RESULTS: The output
factors of EPID were in agreement with the reference data for field sizes down to
2 cm * 2 cm and for 2 cm * 2 cm; the difference in output factors was +2.06% for
6 MV and +1.56% for 15 MV. For the lowest field size studied (0.8 cm * 0.8 cm),
the differences were maximum; +16% for 6 MV and +23% for 15 MV photon beam. EPID
profiles of both energies were closely matching with reference profiles for field
sizes down to 2 cm * 2 cm; however, penumbra and measured field size of EPID
profiles were slightly lower compared to its counterpart. CONCLUSIONS: EPID is a
viable option for profile and output factor measurements for field sizes down to
2 cm * 2 cm in the absence of appropriate small field dosimeters.
PMID- 28706351
TI - Beam Characterization of 10-MV Photon Beam from Medical Linear Accelerator
without Flattening Filter.
AB - AIM: This work investigated the dosimetric properties of a 10-MV photon beam
emitted from a medical linear accelerator (linac) with no flattening filter (FF).
The aim of this study is to analyze the radiation fluence and energy emitted from
the flattening filter free (FFF) linac using Monte Carlo (MC) simulations.
MATERIALS AND METHODS: The FFF linac was created by removing the FF from a linac
in clinical use. Measurements of the depth dose (DD) and the off-axis profile
were performed using a three-dimensional water phantom with an ionization
chamber. A MC simulation for a 10-MV photon beam from this FFF linac was
performed using the BEAMnrc code. RESULTS: The off-axis profiles for the FFF
linac exhibited a chevron-like distribution, and the dose outside the irradiation
field was found to be lower for the FFF linac than for a linac with an FF (FF
linac). The DD curves for the FFF linac included many contaminant electrons in
the build-up region. CONCLUSION: Therefore, for clinical use, a metal filter is
additionally required to reduce the effects of the electron contamination. The
mean energy of the FFF linac was found to be lower than that of the FF linac
owing to the absence of beam hardening caused by the FF.
PMID- 28706352
TI - Monte Carlo Calculation of Beam Quality and Phantom Scatter Corrections for
Lithium Formate Electron Paramagnetic Resonance Dosimeter for High-energy
Brachytherapy Dosimetry.
AB - PURPOSE: To investigate beam quality correction, KQQ0 (r) and phantom scatter
correction, Kphan (r) for lithium formate dosimeter as a function of distance r
along the transverse axis of the high-energy brachytherapy sources 60Co, 137Cs,
192Ir and 169Yb using the Monte Carlo-based EGSnrc code system. MATERIALS AND
METHODS: The brachytherapy sources investigated in this study are BEBIG High Dose
Rate (HDR) 60Co (model Co0.A86), 137Cs (model RTR), HDR 192Ir (model
Microselectron) and HDR 169Yb (model 4140). The solid phantom materials
investigated are PMMA, polystyrene, solid water, virtual water, plastic water,
RW1, RW3, A150 and WE210. RESULT: KQQ0 (r) is about unity and distance
independent fo 60Co, 137Cs and 192Ir brachytherapy sources, whereas for the 169Yb
source, KQQ0 (r) increases gradually to about 4 % larger than unity at a distance
of 15 cm along the transverse axis of the source. For 60Co source, phantoms such
as polystyrene, plastic water, solid water, virtual water, RW1, RW3 and WE210 are
water-equivalent but PMMA and A150 phantoms show distance-dependent Kphan (r)
values. For 137Cs and 192Ir sources, phantoms such as solid water, virtual water,
RW1, RW3 and WE210 are water-equivalent. However, phantoms such as PMMA, plastic
water, polystyrene and A150 showed distance-dependent Kphan (r) values, for these
sources. For 169Yb source, all the investigated phantoms show distance-dependent
Kphan (r) values. CONCLUSION: KQQ0 (r) is about unity and distance independent
for 60Co, 137Cs and 192Ir brachytherapy sources. Phantoms such as solid water,
virtual water, RW1, RW3 and WE210 are water-equivalent for 60Co, 137Cs and 192Ir
brachytherapy sources. For 169Yb source, all the investigated phantoms show
distance-dependent Kphan (r) values.
PMID- 28706353
TI - A Dosimetric Study on Slab-pinewood-slab Phantom for Developing the Heterogeneous
Chest Phantom Mimicking Actual Human Chest.
AB - The aim is to study the density, isodose depths, and doses at different points in
slab-pinewood-slab (SPS) phantom, solid phantom SP34 (made up of polystyrene),
and chest level of actual patient for developing heterogeneous chest phantom
mimicking thoracic region of human body. A 6 MV photon beam of field size of 10
cm * 10 cm was directed perpendicular to the surface of computed tomography (CT)
images of chest level of patient, SPS phantom, and SP34 phantom. Dose was
calculated using anisotropic analytical algorithm. Hounsfield units were used to
calculate the density of each medium. Isodose depths in all the three sets of CT
images were measured. Variations between planned doses on treatment planning
system (TPS) and measured on linear accelerator (LA) were calculated for three
points, namely, near slab-pinewood interfaces (6 and 18 cm depths) and 10 cm
depth in SPS phantom and at the same depths in SP34 phantom. Density of pinewood,
SP34 slabs, chest wall, lung, and soft tissue behind lung was measured as 0.329
+/- 0.08, 0.999 +/- 0.02, 0.898 +/- 0.02, 0.291 +/- 0.12, and 1.002 +/- 0.03
g/cc, respectively. Depths of 100% and 90% isodose curves in all the three sets
of CT images were found to be similar. Depths of 80%, 70%, 60%, 50%, and 40%
isodose lines in SPS phantom images were found to be equivalent to that in chest
images, while it was least in SP34 phantom images. Variations in doses calculated
at 6, 10, and 18 cm depths on TPS and measured on LA were found to be 0.36%,
1.65%, and 2.23%, respectively, in case of SPS phantom, while 0.24%, 0.90%, and
0.93%, respectively, in case of SP34 slab phantom. SPS phantom seemed equivalent
to the chest level of human body. Dosimetric results of this study indicate that
patient-specific quality assurance can be done using chest phantom mimicking
thoracic region of human body, which has been fabricated using polystyrene and
pinewood.
PMID- 28706354
TI - Intensities of Incident and Transmitted Ultraviolet-A Rays through Gafchromic
Films.
AB - Gafchromic films have been applied to X-ray dosimetry in diagnostic radiology. To
correct nonuniformity errors in Gafchromic films, X-rays in the double-exposure
technique can be replaced with ultraviolet (UV)-A rays. Intensities of the
incident and transmitted UV-A rays were measured. However, it is unclear whether
the chemical color change of Gafchromic films affects the UV-A transmission
intensity. Gafchromic EBT3 films were suitable to be used in this study because
non-UV protection layers are present on both sides of the film. The film is
placed between UV-A ray light-emitting diodes and a probe of a UV meter.
Gafchromic EBT3 films were irradiated by UV-A rays for up to 60 min. Data for
analysis were obtained in the subsequent 60 min. Images from before and after UV
A irradiation were subtracted. When using 375 nm UV-A, the mean +/- standard
deviation (SD) of the pixel values in the subtracted image was remarkably high
(11,194.15 +/- 586.63). However, the UV-A transmissivity remained constant
throughout the 60 min irradiation period. The mean +/- SD UV-A transmission
intensity was 184.48 +/- 0.50 MUm/cm2. Our findings demonstrate that color
density changes in Gafchromic EBT3 films do not affect their UV-A transmission.
Therefore, Gafchromic films were irradiated by UV-A rays as a preexposure.
PMID- 28706355
TI - The Influence of Acquisition Mode on the Dosimetric Performance of an Amorphous
Silicon Electronic Portal Imaging Device.
AB - AIMS: This study investigates the impact of cine acquisition mode on the
dosimetric characteristics of a Varian aS500 amorphous silicon electronic portal
imaging device (a-Si EPID). MATERIALS AND METHODS: The performance of an a-Si
EPID operated in cine mode was assessed and compared to its performance when
operated in an integrated mode and dose measurements using an ionization chamber.
This study was conducted at different photon energies and the EPID performance
was assessed as function of the delivered dose, dose rate, multileaf collimator
speed, field size, phantom thickness, and intensity-modulated radiation therapy
fields. RESULTS: The worst nonlinearity was observed at low monitor unit (MU)
settings < 100 MU with the highest dose per frame. The nonlinearity of response
at a low MU setting was attributed due to the loss of four cine images during
each delivery. The EPID response with changing dose rate for 10 MU delivered had
similar results to its performance in an integrated mode and ionization chamber.
Despite the nonlinearity of response with low MU delivered, EPID performance
operated in cine and integrated acquisition modes had comparable responses within
2%. CONCLUSIONS: For EPID dosimetry application using cine mode, this study
recommends the calibration of the EPID images to be undertaken at a large MU.
There were no additional corrections that were required when the EPID operated in
cine acquisition mode as compared to calibration in integrated mode.
PMID- 28706356
TI - Radioactive Cobalt-60 Teletherapy Machine - Estimates of Personnel Dose in Mock
Emergency in Patient Release during "Source Stuck Situation".
PMID- 28706357
TI - Reference to: Chen YG, Li AC, Li WY, Huang MY, Li XB, Chen MQ, et al. The
Feasibility Study of a Hybrid Coplanar Arc Technique versus Hybrid Intensity
modulated Radiotherapy in Treatment of Early-stage Left-sided Breast Cancer with
Simultaneous-integrated Boost. J Med Phys 2017;42:1-8.
PMID- 28706358
TI - Response to the comments on "The Feasibility Study of a Hybrid Coplanar Arc
Technique versus Hybrid Intensity-modulated Radiotherapy in Treatment of Early
stage Left-sided Breast Cancer with Simultaneous-integrated Boost. J Med Phys
2017;42:1-8".
PMID- 28706359
TI - Medical Management of Symptomatic Fibroids: Worth It?
PMID- 28706360
TI - Osteoporosis Prevention and Management.
AB - Osteoporosis, defined by BMD at the hip or lumbar spine that is less than or
equal to 2.5 standard deviations below the mean BMD of a young-adult reference
population, is the most common bone disease in humans affecting both sexes and
all races. It's a silent killer affecting the quality of life due to fractures
and postural changes. In osteoporosis there is an imbalance between bone
formation and bone resorption in favor of latter. Preventive measures and
treatments are available to combat this evil. Counseling is the integral part of
prevention as well as treatment of osteoporosis. Preventive strategy includes
life style changes, exercise, intake of calcium and vitamin D, avoiding alcohol,
smoking and excessive intake of salt. Estrogen therapy/estrogen+progesterone
therapy (ET/EPT) is no longer recommended as a first-line therapy for the
prevention of osteoporosis. They may be used in the therapy for osteoporosis in
women under 60. Diagnosis and classification are made by assessment of BMD using
DEXA or ultrasound and laboratory investigations. Management includes estimation
of 10-year fracture risk using FRAX, life style and diet modification and
pharmacological therapy. The drugs used in osteoporosis may be those that inhibit
bone resorption-bisphosphonates, denosumab, calcitonin, SERMs, estrogen and
progesterone-or that stimulate bone formation-PTH, Teriparatide. Combination
therapies are not recommended as they do not have proven additional BMD/fracture
benefits. No therapy should be indefinite in duration. There are no uniform
recommendations to all patients. Duration decisions need to be individualized.
While on treatment monitoring should be done with BMD assessment by
DEXA/ultrasound and bone turnover markers.
PMID- 28706361
TI - Opportunistic Salpingectomy as an Ovarian Cancer Primary Prevention Strategy.
AB - Ovarian cancer is the most lethal form of all gynecologic malignancies. The
presenting clinical symptoms of ovarian cancer are very vague and often appear
late in the course of disease. Hence, most patients are diagnosed at later
stages. At present, there is no effective screening of ovarian cancer. Primary
prevention could be considered a strategy to decrease the mortality from ovarian
cancer, not only in women at high risk but also in those at low risk. Most
"ovarian cancers," and more specifically the high-grade serous carcinoma (HGSC)
subtype of ovarian cancer, actually could originate in the fallopian tube. Women
who have known BRCA1 or BRCA2 germline mutations should be counseled regarding
bilateral salpingo-oophorectomy, immediately after completion of childbearing, as
the best strategy for reducing their risk of developing ovarian cancer. If the
patient is reluctant, they should be counseled regarding risk-reducing
salpingectomy when childbearing is complete followed by oophorectomy in the
future. For women at average risk of ovarian cancer, risk-reducing salpingectomy
should also be discussed and considered with patients at the time of any
abdominal or pelvic surgery, hysterectomy or tubal ligation.
PMID- 28706362
TI - Pregnancy-Associated Plasma Protein A Levels in Late First Trimester Pregnancies
with Small-for-Gestational Age Neonates: A Prospective Case-Control Study.
AB - OBJECTIVE: We aimed to investigate the association of pregnancy associated plasma
protein A (PAPP-A) levels in late first trimester with small for gestational age
(SGA) neonates and adverse pregnancy outcomes in a low-income setting. METHODS:
The inclusion criteria were late first trimester (11-13 + 6 weeks) women with
singleton and non-anomalous pregnancy. Enrolled participants were sampled for
PAPP-A and prospectively followed up for delivery outcome and antenatal
complications. A multiple of median (MoM) was calculated and statistically
compared between groups. RESULTS: Out of total 284 subjects, 14.54% delivered SGA
babies and formed cases (Group A), 66.5% delivered appropriate for gestational
age (AGA) neonates with uneventful antenatal period (controls, Group B), and
19.3% were AGA group with adverse pregnancy complications (Group C). The late
first trimester median PAPP-A MoM was significantly lower (0.61) in Group A
compared to Group B (1.47). Using receiver operating characteristic (ROC) curve
for PAPP-A MoM, optimal cutoff value was found at 0.45 MoM, with positive
predictive value of 56.2%, specificity of 92.6% and sensitivity of 45%. The
median interquartile range (IQR) of PAPP-A MoM value in Group C in comparison
with Group B was significantly lower except for abruption. At PAPP-A MoM cutoff
value <1, <0.8, <0.6 and <0.4, the odds ratio for adverse pregnancy outcome was
8.30, 7.29, 10.97 and 10.60, respectively, indicating an inverse relationship.
CONCLUSION: With 0.45 MoM cutoff of PAPP-A, the detection rate, specificity and
positive predictive value for SGA were 45, 92.6 and 56.2%, respectively. As PAPP
A MoM values decreased, the odds ratio of having adverse pregnancy outcomes
increased.
PMID- 28706363
TI - Comparative Study of Efficacy and Safety of Ferric Carboxymaltose Versus Iron
Sucrose in Post-partum Anaemia.
AB - BACKGROUND: The incidence of post-partum anaemia (PPA) is 14-24%. Treatment of
PPA with injectable iron replenishes the iron store. Ferric carboxymaltose
complex (FCM) is a non-dextran containing intravenous iron agent, having a very
low immunogenic potential, designed to be administered in large doses in a short
period of time. OBJECTIVE: To compare the efficacy and safety of intravenous FCM
and iron sucrose (IS) in post-partum iron-deficiency anaemia. MATERIAL AND
METHOD: In this prospective, comparative study, 120 post-partum women with iron
deficiency anaemia (Hb < 10 g%) were divided into two groups. A fixed dose of
1000 mg of FCM or IS was given within 10 days of delivery. Hb and serum ferritin
were repeated 14 days post-transfusion. RESULT: There is a mean increase in Hb (P
value 0.000, 0.000) and ferritin (P value 0.000, 0.000) in both the groups. For
intergroup comparison, independent Student's t test was performed which showed
FCM was superior to IS (P value 0.000 and 0.000). CONCLUSION: In our study, FCM
was very effective in improving Hb concentration as well as in early
replenishment of iron stores in patients with PPA. Large doses given in a short
period of time not only save hospital resources but also improve patient
satisfaction. It has significant benefit for use in the outpatient department.
From this study, we can recommend its use in post-partum women with iron
deficiency anaemia.
PMID- 28706364
TI - Prediction of Preeclampsia in Early Pregnancy by Estimating the Spot Urinary
Albumin/Creatinine Ratio.
AB - OBJECTIVE: To assess whether a spot urinary albumin:creatinine ratio (ACR)
measured before 20 weeks of gestation can predict subsequent development of
preeclampsia. METHODS: The ACR was determined from midstream urine sample taken
between 17 and 20 weeks of gestation. Urine albumin was measured by
immunoturbidimetric method using commercially available kit (Beckman Coulter)
through Beckman AU 480 fully automated biochemistry analyzer. Urine creatinine
was measured by modified kinetic Jaffe reaction without
deproteinization.[Formula: see text]Participants were then followed until
delivery. Primary outcome measure was preeclampsia, secondary outcome measures
were gestational hypertension, gestational diabetes mellitus, IUGR, and normal
range estimate of urinary albumin-to-creatinine ratio was established. RESULT:
The median spot urinary albumin-to-creatinine ratio measured between 17 and 20
weeks of gestation was 5.2 mg/g of creatinine (2.5-9.6). Women who subsequently
developed preeclampsia had higher spot urinary albumin-to-creatinine ratio
(median 30.795 [9.7-92.8]) in comparison with women who developed gestational
hypertension (median 5.2 [0.7-7.2]) and unaffected women (median 5.2 [2.5-9.6]).
The urinary albumin-to-creatinine ratio of the mother who developed IUGR was
significantly higher. By ROC analysis, the optimum ACR to predict preeclampsia
was 9.85 mg/g of creatinine. The relative risk of developing preeclampsia in
women with urinary albumin-to-creatinine ratio more than 9.85 mg/g of creatinine
was higher than in the women who had urinary albumin-to-creatinine ratio less
than 9.85 mg/g of creatinine. CONCLUSION: A spot urinary albumin-to-creatinine
ratio of more than 9.8 mg/g of creatinine can predict the development of
preeclampsia in later pregnancy with the sensitivity and specificity of 67 and
76%, respectively. However, additional studies and cost-benefit analysis are
required to confirm these finding before recommending this test for screening
purposes.
PMID- 28706365
TI - Obstetric Outcome in Women with Chronic Liver Disease.
AB - AIM: This study determines the prevalence, causes and outcome of pregnancy in
women with chronic liver diseases in a tertiary level teaching institute in
Southern India. METHODS: Retrospective analysis of case records was carried out
between December 2010 and May 2015 in the departments of Obstetrics and
Gynecology and Gastroenterology including pregnant women diagnosed to have
chronic liver diseases prenatally or during pregnancy. RESULTS: The frequency of
chronic liver disease in pregnancy was 50 among 10,823 deliveries (0.4%). Twenty
six women with chronic liver disease had 50 pregnancies during the study period.
Fifty percent of the women had cirrhosis. Maternal complications occurred in 22%
of the study group. Variceal hemorrhage occurred in 4%, and hepatic
decompensation occurred in 16%. There were two maternal deaths (4%). Obstetric
complication such as preeclampsia, postpartum hemorrhage and puerperal infection
occurred in 18, 14 and 18%, respectively. Abortion occurred in 34%, 55% in
cirrhotic and 4.8% in non-cirrhotic. Live birth rate of 76% was significantly
higher (p < 0.014) in the non-cirrhotic group compared to cirrhotic group.
CONCLUSION: Pregnancies in chronic liver disease are associated with high rate of
abortions. Live birth rates are better and complications such as variceal
bleeding or decompensation of liver disease are less common than previously
reported.
PMID- 28706366
TI - GnRH Antagonist Cetrorelix Administration Before hCG for Protection of Ovarian
Hyperstimulation Syndrome.
AB - OBJECTIVE: Studying the effect of GnRH antagonist administration on the day of
hCG to cases of IVF/ICSI with estradiol level above 5000 ng/dl for protection of
ovarian hyperstimulation syndrome. DESIGN: Prospective study. MATERIALS AND
METHODS: Sixty patients undergoing controlled hyperstimulation COH, for IVF/ICSI
using long agonist and E2 level on the day of hCG, are above 5000 ng/dl, 52
patients received single dose of cetrorelix 0.25 mg on the day of hCG, and 8
patients received two doses of 0.25 mg/day cetrorelix started one day before the
day of hCG. RESULTS: There was no significant difference regarding patients BMI,
number of stimulation days, recombinant FSH dose, and number of retrieved
oocytes. Clinical pregnancy rate was 76.6% (46/60), in patients received single
dose of antagonist PR were significantly higher 80.7% (42/52) versus 50% (4/8) in
patients received two doses p = 0.047. Live birth rate was 50% (30/60), abortion
rate was 20% (12/60), and preterm delivery was 20% (12/60). Mean E2 was 6853.2
ng/dl. Six patients developed moderate ovarian hyperstimulation OHSS (6/60) 10%
and no cases of severe OHSS. CONCLUSIONS: GnRH antagonist administration on the
day of hCG in cases undergoing IVF/ICSI with long agonist protocol is effective
in protection of OHSS and does not affect the clinical pregnancy rate nor live
birth rate.
PMID- 28706367
TI - Diagnostic Office Vaginohysteroscopy in Evaluation of Infertility Prior to IVF: A
Retrospective Analysis of 1000 Cases.
AB - AIM: The aim of this study was to analyze the utility of routine use of
diagnostic office vaginohysteroscopy in the evaluation of uterine cavity in
infertility patients prior to IVF-ET. MATERIALS AND METHODS: We conducted a
retrospective analysis of 1000 women who had undergone routine diagnostic office
vaginohysteroscopy as an institutional protocol in the evaluation of infertility
prior to IVF-ET cycle at a tertiary care hospital. They were divided into two
groups: primary infertility (group I) and secondary infertility (group II). The
primary outcome was the finding of an abnormal uterine cavity (congenital
abnormality vs acquired abnormality). RESULTS: One thousand women underwent
routine diagnostic office vaginohysteroscopy in the evaluation of infertility
prior to IVF-ET. There were no intraoperative or postoperative complications.
Vaginohysteroscopy revealed an abnormal uterine cavity in 13.8% (1000 patients)
of women. Primary infertility group (I) had 13.19% (811 patients), and secondary
infertility group (II) had 16.4% (189 patients) abnormal uterine cavities.
CONCLUSION: Diagnostic office vaginohysteroscopy has a definite role in the
uterine cavity evaluation in infertility patients prior to IVF, but routine use
should not be recommended considering the low incidence of abnormal uterine
cavity findings. Moreover, the majority of these uterine cavity abnormalities can
be detected by less invasive tests such as HSG, TVS, SSG and 3D ultrasound.
PMID- 28706368
TI - Knowledge and Behaviour Regarding Birth Prevention of Healthcare Providers.
AB - INTRODUCTION: Healthcare providers are an important link with the general public
to impart knowledge regarding contraception. They are an important source of
providing information regarding different methods of contraception, their proper
use and removing the myths from the couple's mind. However, their own attitude
and practice of contraception are often lacking. OBJECTIVE: This study was
conducted to assess the attitude and practice of contraception over the last 1
year of nurses in a tertiary care hospital in Jaipur. METHODS: The study was
conducted on 410 nurses in a tertiary care hospital. All were given a
questionnaire that was duly filled by them, and the data obtained was analysed.
RESULTS: All were aware of at least one family planning method. Only 84% knew
that contraceptives could space the pregnancy. Very few had correct knowledge
about the fertile period or lactational amenorrhoea. Few were aware of emergency
contraception and its proper implication (6.83%) The commonest was the barrier
method (70%) followed by natural method (41.46%). There was shifting from natural
method to barrier method and OC pills for few cycles. CONCLUSION: Health workers
have knowledge regarding contraception yet fail to use it regularly. Proper
attitude and practice are essential to prevent unintended pregnancies and
prevention of STDs. Their use will enhance counselling skills for general
population.
PMID- 28706369
TI - Improving the Knowledge and Attitude on 'Standard Days Method' of Family Planning
Through a Promotional Program Among Indian Postgraduate Students.
AB - INTRODUCTION: The 'Standard Days Method' is a fertility awareness-based method of
family planning that identifies day 8 through day 19 of the menstrual cycle as
fertile days during which a woman is likely to conceive with unprotected
intercourse. OBJECTIVE: The study was aimed to determine the effectiveness of a
promotional program on the 'Standard Days Method' in terms of improving the
knowledge scores and attitude scores. DESIGN: A pre-experimental one-group
pretest-posttest research design was adopted. The samples included 365 female
postgraduate students from selected colleges of Udupi Taluk, Karnataka. The data
was collected using self-administered questionnaires. The plan for the
promotional program was also established. RESULTS: The findings of the study were
analyzed using the descriptive and inferential statistics. The mean pretest and
posttest knowledge scores were computed, and it was found that there was an
increase in the mean knowledge score from 8.96 +/- 3.84 to 32.64 +/- 5.59,
respectively. It was observed that the promotional program on 'Standard Days
Method' was effective in improving the knowledge (p < 0.001) and attitude (p <
0.001) of the postgraduate students. CONCLUSION: The promotional program on
Standard Days Method of family planning was effective in improving the knowledge
and attitude of the postgraduate female students. This will enable the women to
adopt this method and plan their pregnancies naturally and reduce the side
effects of using oral contraceptives.
PMID- 28706370
TI - Splenic Pregnancy: A Case Report.
PMID- 28706371
TI - Growing Teratoma Syndrome Following Treatment for Immature Teratoma of Ovary-A
Case Report and Review of Literature.
PMID- 28706372
TI - Second Look of Endosalpingiosis: A Rare Entity.
PMID- 28706373
TI - Tao Brush.
PMID- 28706374
TI - Falope Ring or Modified Pomeroy's Technique for Concurrent Tubal Sterilization.
PMID- 28706375
TI - Hepatotoxicity and Ultra Structural Changes in Wistar Rats treated with Al2O3
Nanomaterials.
AB - The present study was designed to evaluate the hepatotoxicity of aluminium oxide
(Al2O3). To achieve this objective, Al2O3 of three different sizes (30nm, 40nm
and bulk) was orally administered for 28 days to 9 groups of 10 Wistar rats each,
at the dose of 500, 1000 and 2000 mg/Kg/rat. A tenth group of 10 rats received
distilled water and served as control. After 28 days of exposure, the animals
were sacrificed and the serum was collected and tested for the activity levels of
aminotransferases (AST or GOT and ALT or GPT), alkaline phosphatase (ALP) and
lactate dehydrogenase (LDH) enzymes following standard testing methods. Reduced
glutathione (GSH) content was also measured in the liver tissue to study the
oxidative stress. A histopathological evaluation was also performed to determine
the extent of liver injury. Study results indicated that the activity of both the
aminotransferases (AST and ALT), ALP and LDH increased significantly in Al2O3
treated rats compared to control animals. The increase was found to be more
pronounced with Al2O3 - 30nm followed by Al2O3 - 40nm and Al2O3 - bulk treated
rats in a dose dependent manner. However reduced glutathione content showed a
decline in the activity. Ultra structural assessment showed significant
morphological changes in the liver tissue in accordance with biochemical
parameters. Taken together, the results of this study demonstrated that Al2O3 is
hepatotoxic and the smaller size of this nanomaterial appeared to be the most
toxic while the compound in the bulk form seemed to be the least toxic.
PMID- 28706376
TI - Axillary artery injury and brachial plexus palsy as a complication of proximal
humerus fractures.
PMID- 28706377
TI - Nationwide survey of pediatric septic arthritis in the United States.
AB - BACKGROUND: The epidemiology of pediatric septic arthritis, such as annual
hospitalization rates and disparities by age, gender, race/ethnicity, and
socioeconomic status, remains unclear. METHODS: We obtained hospital discharge
records of patients under the age of 20 years with septic arthritis from the kids
inpatient database for 2006, 2009 and 2012. We weighted the records to estimate
the number of hospitalizations in the US and calculated the annual rates of
hospitalization due to septic arthritis. We used multivariable logistic
regression to assess risk factors associated with comorbidities of osteomyelitis
and bacteremia/septicemia. RESULTS: Overall annual hospitalization rates showed a
decreasing trend (4.23, 3.64, and 3.28 per 100,000 children in 2006, 2009, and
2012, respectively). Children who were male, white or black, and between the ages
of 0-4 years were more likely to have higher hospitalization rates than others.
The proportions of hospitalizations were high among children living in lower
income areas. Large joints at the lower limbs were the most frequently affected
sites of infection. Infections of large joints and age category of 10-14 years
were the factors that were significantly associated with comorbidities of
osteomyelitis and bacteremia/septicemia. CONCLUSIONS: We demonstrated a change in
the epidemiological patterns of pediatric septic arthritis and identified risk
factors associated with comorbidities of osteomyelitis and bacteremia/septicemia.
PMID- 28706378
TI - Soft-tissue damage during total knee arthroplasty: Focus on tourniquet-induced
metabolic and ionic muscle impairment.
AB - PURPOSE: Advantages of tourniquet use in TKA include benefits for surgeons and
patients, varying from a bloodless operation site to a reduced intervention time.
The time under ischemia and the reperfusion period are crucial phases for
affected soft-tissue, most commonly the extensor mechanism. CASE REPORTS:
documented its impact on soft-tissue, ranging from necrotic muscle damage to
systemic inflammation. Recently, research regarding tourniquet application
patterns discuss clinical outcome parameters in the context of soft-tissue
damage, excluding the underlying pathophysiological mechanisms. METHODS: This
review summarizes the molecular aspects of soft-tissue damage occurring during
tourniquet application in TKA with special focus on ischemia/reperfusion injury.
Recent meta-analyses and original trials were reviewed for data on muscle damage
and are presented. CONCLUSION: Although underlying pathomechanisms are well known
and presented, clinical orthopedic research has so far not addressed this issue.
In context of physical training, positive effects regarding postoperative
recovery might be possible if more attention is paid to prepare involved muscle
preoperatively to TKA (prehabilitation).
PMID- 28706379
TI - Plasma level of Osteopontin does not respond to total replacement Surgery in
patients with severe Primary knee/Hip Osteoarthritis.
AB - OBJECTIVE: To test the response of Osteopontin levels in patients with knee/hip
Osteoarthritis undergoing a replacement surgery. METHOD: Plasma samples of 30 (16
with knee Osteoarthritis and 14 with hip Osteoarthritis) patients have been
collected before and 3 month after a knee/hip replacement in order to investigate
the above stated aim of this study. RESULT: Osteopontin levels did not decrease
after 3 months of the surgery. CONCLUSION: Osteopontin levels showed no
significant reduction and therefore do not respond to replacement treatment.
PMID- 28706380
TI - Importance of anterior humeral line for successful anatomical reduction in the
surgical treatment of pediatric supracondylar humeral fractures.
AB - Anterior humeral line (AHL) and tilting angle (TA) are used for the assessment of
pediatric elbow sagittal plane alignment in surgical treatment of pediatric
supracondylar humeral fracture. However, few studies exist that compare the
reliabilities between these parameters. The purpose of this study is to determine
whether measurements of radiographic parameters are reliable and useful for
achieving anatomical reduction. In the current study, we demonstrated that the
identifying the AHL location involves a simple and reliable measurement compared
with TA. The intraoperative AHL identification is a good indicator for achieving
anatomical reduction.
PMID- 28706381
TI - Concurrent femoral and tibial osteotomies versus soft tissue balance in total
knee arthroplasty: A technical case report.
AB - This case report outlines some of the challenges as well as limitations in
correction of osteoarthritis of the knee in combination with extra-articular
deformities,and provides a novel and straightforward surgical solution in
overcoming these challenges. We describe the case of a 37-year-old male who
suffered from advanced bilateral tri-compartmental knee arthritis due to
untreated bloodstream-sourced osteomyelitis after birth. Radiographs and surgery
confirmed extremely severe deformities. We performed two different surgical
techniques in order to correct extra-articular deformities (one-stage approach of
concurrent tibial and femoral osteotomy and total knee arthroplasty on one side,
and soft tissue balancing with "pie-crusting technique" plus total knee
arthroplasty on the other side), with description of subsequent results at 36
months follow-up.
PMID- 28706382
TI - Cementless acetabular component with or without upward placement in dysplasia
hip: Early results from a prospective, randomised study.
AB - BACKGROUND: Total hip arthroplasty (THA) in developmental dysplasia of hip (DDH)
is difficult for the abnormal acetabulum. The purpose of this study was to
evaluate the difference of anatomic and upward placement of acetabular component
during early stage. METHODS: From April 2014 through June 2015, forty DDH
patients (Crowe I to III, 42 hips) were prospectively randomized to either
anatomic or upward group. Patient recorded diaries were collected. Radiographs
were reviewed. WOMAC and Harris scores were tabulated from pre-operation to 12
months after surgery. RESULTS: The patients' characteristics including age and
body mass index (BMI) had no significant difference (P > 0.05). There were no
statistically differences between two groups for surgery time, intraoperative
blood loss, hemoglobin (Hb), blood transfusion, albumin decrease, length of stay
day, but surgery time and blood loss in patients with structural bone graft was
much higher in anatomic group. The postoperative limb-length discrepancy (LLD)
was also no difference, but limb lengthening was better in anatomic group (P =
0.042). The total hospital costs in the anatomic group were higher, but no
significant differences. With regard to Harris and WOMAC score, there were
significant improved after surgery in both groups, and the anatomic group was
better in the value, but these differences were no statistically significant.
CONCLUSIONS: Acetabular reconstruction for DDH subluxation should be
reconstructed as close to the actual acetabular location as possible, but an
appropriate (<20 mm) upward placement that can achieve at least 70% native bone
coverage of the acetabular implant is a valuable technique for early faster
recovery.
PMID- 28706383
TI - A clinico-pathological study of lupus nephritis based on the International
Society of Nephrology-Renal Pathology Society 2003 classification system.
AB - INTRODUCTION: Lupus nephritis (LN) is a major complication of systemic lupus
erythematosus (SLE). Renal involvement is a major determinant of the prognosis of
SLE. The histological classification of LN is a key factor in determining the
renal survival of patients with LN. Prompt recognition and treatment of renal
disease are important, as early response to therapy is correlated with better
outcome and renal biopsy plays an important role in achieving this. OBJECTIVES:
The objective of this study was to correlate the clinical and laboratory findings
with histopathological classes of LN as per the 2003 International Society of
Nephrology-Renal Pathology Society (ISN/RPS) classification system. PATIENTS AND
METHODS: Fifty-six patients with SLE, undergoing a renal biopsy for renal
dysfunction were studied. The comparison of data from multiple groups was made by
Pearson's Chi-square test and between two groups by independent samples t-test.
The values of P < 0.05 were considered statistically significant. RESULTS: Of the
56 cases studied, 51 (91.1%) were females. The most common presenting symptoms
were edema, arthralgia, and hypertension. Class IV (55.4%) was the most common
class. Thirty-nine (69.6%) cases showed full house immunostaining. Hypertension,
hematuria, proteinuria, and tubulo-interstitial disease showed a significant
correlation (P < 0.05) with ISN/RPS classification, 2003. CONCLUSION: Assessment
and management of patients with suspected LN are greatly facilitated through
information obtained by renal biopsy. Since renal morphology may predict long
term prognosis, and no clinical or laboratory feature uniformly predicts
prognosis, it is important to study the constellation of features in LN for
better patient management.
PMID- 28706384
TI - Antimicrobial susceptibility, risk factors and prevalence of bla cefotaximase,
temoneira, and sulfhydryl variable genes among Escherichia coli in community
acquired pediatric urinary tract infection.
AB - INTRODUCTION: The emergence of extended-spectrum beta-lactamase (ESBL)-producing
Escherichia coli has become an important challenge among pediatric patients with
community-acquired urinary tract infection (UTI). OBJECTIVES: The aim of this
study was to assess the antimicrobial susceptibility patterns, associated risk
factors and to survey the frequency of bla cefotaximase (CTX-M), bla temoneira
(TEM), and bla sulfhydryl variable (SHV) genotypes in ESBL-producing E. coli
isolated from children with community-acquired UTI. METHODS: This was a
prospective study conducted from November 2012 to March 2016 in a tertiary care
center. E. coli isolated in urine cultures from children aged <=18 years was
identified and confirmed for ESBL production. ESBL-positive strains were screened
for ESBL encoding genes. Chi-square test and Fisher's exact test were used to
compare the difference in antibiotic susceptibility with respect to ESBL positive
and negative, and binary logistic regression was used to identify the risk
factors associated with ESBL production. RESULTS: Among 523 E. coli isolates, 196
(37.5%) were ESBL positive, >90% were resistant to cephalosporins, and 56% were
resistant to fluoroquinolones. Least resistance was observed for imipenem,
netilmicin, and nitrofurantoin (2%, 8.6%, 15.3%). Association between ESBL
production and drug resistance was significant for ceftazidime (P < 0.001),
cefixime (P < 0.001), cefotaxime (P = 0.010), ceftazidime-clavulanic acid (P <
0.001), levofloxacin (P = 0.037), and gentamicin (P = 0.047) compared to non-ESBL
E. coli. CTX-M gene was the most prevalent (87.5%), followed by TEM (68.4%) and
SHV (3.1%). Previous history of UTI and intake of antibiotics were the common
risk factors. CONCLUSION: ESBL-producing E. coli from community-acquired
pediatric UTI carries more than one type of beta-lactamase coding genes
correlating their increased antibiotic resistance. Aggressive infection control
policy, routine screening for detecting ESBL isolates in clinical samples, and
antimicrobial stewardship are the keys to prevent their dissemination in
community settings.
PMID- 28706385
TI - Acylation-stimulating protein is a surrogate biomarker for acute myocardial
infarction: Role of statins.
AB - BACKGROUND: Acylation-stimulating protein (ASP) is an adipokine synthesized
within adipocytes environment due to adipocyte differentiation. AIM: The aim of
this study was to assess changes in ASP levels in patients with acute myocardial
infarction (MI) and to correlate these variations with disease variables.
SUBJECTS AND METHODS: A total number of 111 patients previously and currently
treated with rosuvastatin or atorvastatin presented with acute MI in a Coronary
Care Unit, were divided into three groups, Group A: Thirty-nine patients treated
with atorvastatin, Group B: Thirty patients treated with rosuvastatin, compared
to 42 patients presented with MI not previously treated with statins were
enrolled in this study. ASP and troponin-I levels and lipid profile were
estimated in each group. RESULTS: The effects of atorvastatin and rosuvastatin
compared to nonstatins-treated group on the anthropometric and biochemical
variables in patients with acute MI showed significant difference in all
biochemical and anthropometric parameters P < 0.05. Serum ASP (nmol/l) levels
were higher in control patients 57.25 +/- 9.15 compared to atorvastatin-treated
patients 48.43 +/- 7.42 and rosuvastatin-treated patients 49.33 +/- 6.52 P =
0.0124. CONCLUSION: ASP levels are elevated in patients with acute MI and
regarded as surrogate biomarker for acute MI also; therapy with statins leads to
significant reduction in ASP levels compared to nonstatins-treated patients that
presented with acute MI.
PMID- 28706386
TI - Alarming emergence, molecular characterization, and outcome of blaNDM-1 in
patients infected with multidrug-resistant Gram-negative bacilli in a tertiary
care hospital.
AB - INTRODUCTION: This study was conducted to assess the prevalence of metallo-beta
lactamases (MBLs) in general and blaNDM-1 in particular. It also aimed at
evaluating clinical characteristics and outcome in patients infected with MBLs.
MATERIALS AND METHODS: A total of 116 carbapenem-resistant Gram-negative bacilli
(CRGNB) were evaluated in the study. These CRGNB were tested for MBL production
both phenotypically for MBLs and genotypically for blaNDM-1 gene by polymerase
chain reaction (PCR). Representative stains of NDM-1 isolates were further
sequenced by Triyat Scientific Co., (Nagpur, India). RESULTS: Among 116 CRGNB
Citrobacter species 28 (24.13%) was the most common pathogen. Phenotypically,
MHT, imipenem-EDTA (IPM-EDTA) double-disk synergy test and IPM-EDTA combined disk
synergy test (CDST) detected MBL production in 105 (90.51%), 96 (81.03%), and 87
(75%) CRGNB, respectively. However, blaNDM-1 genes were detected in 66 (56.89%)
isolates. The prevalence of blaNDM-1 gene was highest among Escherichia coli 26
(100%). Considering PCR as gold standard, it was observed that IMP-EDTA CDST was
most specific (78.38%) while MHT was most sensitive (97.47%). Results of blaNDM-1
gene by PCR were further confirmed by sequencing (Triyat genomics, Nagpur). All
the 11 representative strains were confirmed to be an NDM-1 gene. The presence of
MBLs in our group of patients (non-Intensive Care Unit patients) is a cause for
concern. However, on tracing their outcome, it was interesting to note that while
the duration of stay lengthened in a large number of patients 112 (96.5%),
mortality was relatively low 5 (4.31%). CONCLUSION: The results of this study
provide insight into the prevalence of MBLs, including blaNDM-1, in a tertiary
care hospital. Antibiotic stewardship implemented in all seriousness may to a
great extent stave off the impending pan-drug resistance. The surprising outcome
of our patients suggests either that the bacteria trade off virulence for drug
resistance or the relatively robust immune response of non ICU patients fights
back.
PMID- 28706387
TI - Comparison of nonstructural protein-1 antigen detection by rapid and enzyme
linked immunosorbent assay test and its correlation with polymerase chain
reaction for early diagnosis of dengue.
AB - INTRODUCTION: Early diagnosis of dengue is important for appropriate clinical
management and vector control. Different serological tests based on the principle
of immunochromatography and enzyme-linked immunosorbent assay (ELISA) are
commonly used for detection of antigen and antibodies of dengue virus. The
performance of these tests depends on the sensitivity and specificity. Hence, the
study was undertaken to compare nonstructural protein-1 (NS1) antigen detection
by rapid and ELISA with real-time polymerase chain reaction (RT-PCR) for
diagnosis of dengue. MATERIALS AND METHODS: Prospective laboratory study was
carried out on sera samples (n = 200) from clinically suspected cases of dengue.
The sera samples were subjected for NS1 antigen detection test by rapid test, NS1
ELISA, and RT-PCR. The results of rapid and ELISA tests were compared with real
Time PCR. RESULTS: The sensitivity, specificity, positive, and negative
predictive value of rapid dengue NS1 antigen test were 81.5%, 66.7%, 78.2%, and
71.1%, respectively whereas that of NS1 ELISA were 89.9%, 100%, 100%, and 94%,
respectively. Concordance of Rapid NS1 and NS1 ELISA with PCR was 75.5% and 94%.
DISCUSSION AND CONCLUSION: NS1 antigen ELISA can be implemented in diagnostic
laboratories for diagnosis of dengue in the acute phase of illness. The test also
has great potential value for use in epidemic situations, as it could facilitate
the early screening of patients and limit disease expansion.
PMID- 28706388
TI - Comparison of bone marrow aspiration cytology with bone marrow trephine biopsy
histopathology: An observational study.
AB - INTRODUCTION: Bone marrow examination is a useful investigative tool for the
diagnosis of many hematological and nonhematological disorders. Bone marrow
aspiration (BMA) provides information about the numerical and cytological
features of marrow cells, whereas bone marrow trephine biopsies (BMB) provide
excellent appreciation of spatial relationships between cells and of overall bone
marrow structure. We conducted this study with the objective of comparing the
accuracy of BMA with BMB in the diagnosis of various hematological disorders.
MATERIALS AND METHODS: Both BMA and BMB were performed on a total of 130 cases
and a comparative evaluation was performed in 100 cases to see the complementary
role of both the procedures. However, 30 cases were excluded due to inadequate
BMA, BMB, or both. Immunohistochemistry (IHC) was employed whenever required.
RESULTS: In our study of 100 cases, 87% of cases were confirmed on bone marrow
biopsy and in remaining 13% of cases final diagnosis was achieved with the help
of other ancillary investigations. These cases were excluded for calculation of
concordance rate between BMA and BMB. The concordance and disconcordance rate
between BMA and BMB was 72.4% and 27.6%, respectively. CONCLUSION: BMA cytology
and trephine biopsy histopathology complement each other and the superiority of
one method over the other depended on the underlying disorder. Furthermore,
application of ancillary techniques such as flow cytometery and IHC proved to be
an additional advantage in further typing of various diseases.
PMID- 28706389
TI - Current mycological profile of onychomycosis in Kashmir valley: A hospital-based
study.
AB - INTRODUCTION: Onychomycosis is a common nail ailment associated with significant
physical and psychological morbidity. It is caused by dermatophytes,
nondermatophytic molds, and yeasts. Increased prevalence in the recent years is
attributed to enhanced longevity, comorbid conditions such as diabetes, avid
sports participation, and emergence of HIV. AIMS AND OBJECTIVES: This study was
undertaken to identify the mycological profile and etiological agents associated
with this infection. MATERIALS AND METHODS: One hundred and twenty-nine cases of
clinically suspected onychomycosis were included in this study. Clinical patterns
were noted, and samples collected from most severely affected nail. They were
subjected to direct microscopy and culture. RESULTS: The microscopic and/or
culture examination was positive in 64.34% of cases. The most common clinical
type was distal lateral subungual onychomycosis in 42 (50.60%) Candida sp. was
the most common fungal agent among yeasts, followed by Trichophyton sp among
dermatophytes and Aspergillus among nondermatophytic molds. Females were affected
more than males and fingernails were affected more frequently than toenails.
CONCLUSION: Onychomycosis is a significant and important disease which can cause
many physical, physiological, and occupational problems, considerably impairing
patient quality of life. Hence, fungal cultures are of paramount importance in
all suspected cases of onychomycosis because the antifungal agent with an
appropriate spectrum of activity can only be used if the underlying fungal
pathogen is identified correctly.
PMID- 28706390
TI - The role of discriminant functions in screening beta thalassemia trait and iron
deficiency anemia among laboratory samples.
AB - INTRODUCTION: Most important differential diagnosis for microcytosis and
hypochromia is beta thalassemia trait (BTT) and iron deficiency anemia. AIM: To
study the utility of discriminant functions (DFs) and red cell indices in
distinguishing BTT and iron deficiency anemia. METHODS: The study is
observational (cross sectional). A total of 350 patients, 43 BTT, and 307 iron
deficiency anemia reflecting actual disease prevalence were included. Their
complete red blood cell parameters, hemoglobin A2, and serum ferritin level
wherever required were obtained. Receiver operator characteristic curve was drawn
for each DF and results compared with other studies. RESULTS: Among the six DFs,
the highest sensitivity (97.7%) and specificity (98.6%) was shown, respectively,
by Shine and Lal (S and L) and England and Fraser index (E and F) in identifying
cases of BTT. Youden index of the Mentzer index (MI) was the highest (69.0) and S
and L, the lowest (13.2) indicating MI to be the most efficient and the S and L,
the least in differentiating the two entities. Red cell distribution width index
(RDWI) showed the highest accuracy (91.6%), whereas S and L showed the least
accuracy (29.6%). CONCLUSION: MI was the most efficient in discriminating BTT
from iron deficiency anemia (IDA). RDWI stands to be the most accurate. S and L
could at best be used as screening tool rather than DF. No study except one
agreed with us because convenient sampling used in other studies generated bias
in their results. Statistically, this study bears far more relevance than other
studies because the sample distribution reflects the prevalence of IDA and BTT in
the community.
PMID- 28706391
TI - Utility of a novel chromogenic medium as a screening method in the detection of
carbapenemase producing Enterobacteriaceae.
AB - INTRODUCTION: With the emergence of multidrug resistant Gram-negative bugs, there
is an urgent need for rapid detection of these resistant organisms. AIM: This
study was performed to assess the utility of a novel chromogenic medium in the
detection of carbapenemase producing Enterobacteriaceae from various clinical
specimens. MATERIALS AND METHODS: A total of 202 isolates of Enterobacteriaceae,
which were resistant to meropenem (10 MUg) disc by standard disc diffusion
method, were analyzed over a period of 6 months. These isolates were subjected to
the modified Hodge test (MHT) and inoculated onto the chromogenic medium.
Following which the results were analyzed. RESULTS: It was observed that 76.73%
of the Enterobacteriaceae gave a positive result on the MHT, 18.31% were negative
and 4.95% gave indeterminate result. While 88.11% produced growth on the
chromogenic medium, 6.93% yielded no growth and 4.95% gave variable results.
Concordance in the results of the two tests was found to be 65.34%. CONCLUSION:
Enterobacteriaceae are emerging to be carbapenem resistant and are responsible
for the soaring rates of Healthcare Associated Infections (HAIs), especially
among critically ill patients. Hence, early detection of the same is important in
controlling HAIs.
PMID- 28706392
TI - Acquired aplastic anemia associated with trisomy eight converting into acute
myeloid leukemia.
AB - Aplastic anemia (AA) is nowadays considered to be a clonal disorder arising from
a defective hematopoietic stem cell developing after a generalized insult to bone
marrow. Immunosuppressive treatment (IST) of AA causes suppression of the target
dominant population of haematopoietic cells allowing the defective non targeted
clones to expand. This may give rise to acute leukemia. Cytogenetic studies for
chromosomal aberrations such as trisomy and monosomy may help in detecting such
conversions. We present a case of acquired AA in a 60-year-old male presenting
with pancytopenia and hypoplastic marrow treated with antithymocyte globulin,
converting into myelodysplastic syndrome and later on acute promyelocytic
leukemia after being in remission for 4 years. The patient was found to have
trisomy 8 on fluorescence in situ hybridization and karyotyping.
PMID- 28706393
TI - Cotrimoxazole, a wonder drug in the era of multiresistance: Case report and
review of literature.
AB - Antimicrobial resistance is one of the greatest threats to human health
worldwide. The rate of development of newer antibiotics is much slower than the
rate of development of antibiotic resistance. A survey reported that it takes 15
years and US$800 million (including preclinical and clinical costs) to bring a
single drug to the market, whereas the reuse of the older drugs for antimicrobial
use takes $17 million, thereby circumventing 40% of the overall cost. The first
case is a patient with nosocomial pyrexia of unknown origin who was given
treatment with tigecycline and cefepime/tazobactam but failed to respond to the
same. However, the patient responded to the treatment with cotrimoxazole. The
second case is a patient with meningitis caused by an atypical zoonotic pathogen,
Staphylococcus chromogenes. This is the first report of human infection with S.
chromogenes, this being a common cause of bovine mastitis. The isolate was
obtained from a patient of neurotrauma who developed meningitis after
decompressive craniotomy. The strain was obtained from cerebrospinal fluid,
blood, and shunt chamber pus. Cotrimoxazole was given for the treatment, and the
patient improved after the treatment. Although the newer antibiotics have
replaced sulfonamides in the treatment of many infections, they are still of
great value and are the agents of choice in many infections. Sulfonamides have
wide antimicrobial activity against both Gram-positive and Gram-negative
bacteria, but their usefulness has diminished with the emergence of resistant
strains. This paper reports cases of two different kinds of infections from a
level 1 trauma center, who failed to respond to the newer antibiotics but showed
a response to administration of cotrimoxazole.
PMID- 28706394
TI - Proximal epithelioid sarcomatous dedifferentiation in secondary chondrosarcoma in
a known case of multiple osteochondromatosis.
AB - Osteochondroma is the most common benign bone tumor. Approximately 15% of
osteochondromas occur as multiple lesions. Multiple osteochondromatosis has a
higher risk of developing chondrosarcomas, which are of low grade with good
prognosis. About 10% of all chondrosarcomas may undergo dedifferentiated change,
which has a poorer prognosis. Dedifferentiated peripheral chondrosarcoma
developing within an osteochondroma is extremely rare. Dedifferentiation usually
occurs in the form of osteosarcoma, malignant fibrous histiocytoma, fibrosarcoma,
or rhabdomyosarcoma. We report a case of proximal epithelioid sarcomatous
dedifferentiation in secondary chondrosarcoma in a 39-year-old male with multiple
osteochondromatosis in bilateral arm. To the best of our knowledge, epithelioid
sarcomatous dedifferentiation has not been described in the literature.
PMID- 28706395
TI - Salmonella typhimurium infection in total knee arthroplasty: A case report with
review of literature.
AB - Salmonella enterica serotype Typhimurium is a rare cause of prosthetic joint
infection (PJI). The recognized predisposing risk factors for Salmonella septic
arthritis include diabetes mellitus, renal failure, human immunodeficiency virus
infection and chronic corticosteroid use. We describe a case of PJI of the knee
in a 74-year-old lady who was on antitubercular treatment. The patient presented
with discharging sinus and raised inflammatory markers. She was successfully
treated by the removal of prosthesis and debridement followed by ciprofloxacin
therapy for 6 weeks. This case report highlights the potential virulence of
Salmonella in immunocompromised patient with a joint prosthesis. Continuous
monitoring and close collaboration of microbiologists and orthopedicians helped
obtain the resolution of infection in our patient.
PMID- 28706396
TI - An atypical presentation of alveolar soft part sarcoma of tongue.
PMID- 28706397
TI - Assessment of Sperm Deoxyribose Nucleic Acid Fragmentation Using Sperm Chromatin
Dispersion Assay.
AB - The integrity of sperm deoxyribose nucleic acid (DNA) is one of the determinants
that ensure normal fertilization, implantation, pregnancy, and the generation of
a healthy progeny. Assessment of sperm DNA fragmentation has gained importance as
a tool to provide significant information regarding sperm quality, and it can
independently predict sperm fertilizing potential. The sperm chromatin dispersion
(SCD) assay is one of the available techniques to detect sperm DNA damage with
results comparable to the gold standard - Sperm Chromatin Structure Assay. We
present here a detailed methodology of an alkaline modification of SCD that can
be carried out with minimal laboratory equipment. The SCD assay is a modified
halo assay that utilizes chemical methods to demonstrate sperm DNA fragmentation.
It involves the embedding of sperms in an agarose medium followed by exposure to
alkaline denaturation and deproteinization. The results are interpreted under a
light microscope. A visual scoring system is utilized to differentiate the sperms
with possible DNA fragmentation from those without fragmented DNA and to
determine the sperm DNA fragmentation index (SDFI) % for each semen sample. The
SDFI % is directly proportional to the quality of sperm. The SCD assay is a
simple, cost-effective, and reliable technique that can detect sperm DNA
fragmentation, thus providing information regarding sperm functional quality and
reproductive capacity. It is of significance in clinical and research areas of
andrology and reproductive medicine, toxicology, and pharmacotherapeutics.
PMID- 28706398
TI - Efficacy of Atorvastatin in Prevention of Contrast-induced Nephropathy in High
risk Patients Undergoing Angiography: A Double-blind Randomized Controlled Trial.
AB - OBJECTIVE: To evaluate the efficacy and safety of atorvastatin (ATN) 80 mg in the
prevention of contrast medium- induced nephropathy (CIN) in high risk patients
undergoing angiograph. MATERIALS AND METHODS: This was a prospective, double
blind, two-arm, parallel group RCT. A total of 216 patients undergoing coronary
angiography were screened, and 188 eligible patients were randomized to two
treatment arms. Patients in Group A received tablet N-acetylcysteine (NAC) 1200
mg once daily, and patients in Group B received tablet atorvastatin 80 mg + NAC
1200 mg once daily, for 3 days before, and 2 days after angiography. RESULTS: A
total of 160 patients completed the trial. Postprocedure, nine and two CIN cases
were found in Group A and B, respectively. The mean change in serum creatinine
was 0.086 +/- 0.168 in Group A and 0.021 +/- 0.083 in Group B, which was
statistically significant (P = 0.0289). Postprocedure, the estimated glomerular
filteration rate was reduced by 19.52 in Group A and 13.55 in Group B (P =
0.003). CONCLUSION: This trial indicates the positive role of statins in
preventive strategy against CIN along with NAC.
PMID- 28706399
TI - Comparative Effect of Divided Doses of Adult Solid and Liquid Oral Formulations
of Antiepileptic Drugs in the Management of Pediatric Epilepsy.
AB - OBJECTIVE: To compare the differences in the efficacy and safety of the commonly
prescribed AEDs in the management of epilepsy in children when using divided
doses of adult solid oral formulations (DDSF) with the liquid oral formulations
(LFs). MATERIALS AND METHODS: Patients who had one or more seizures per month and
prescribed with DDSF were recruited. Initially the patients were continued on
DDSF for 4 months following which they were switched over to LF for the
subsequent 4 months. Seizure frequencies and adverse drug effects (ADRs) were
recorded every month for 8 months and plasma AED levels were estimated at the end
of 4th and 8th months. RESULTS: A total of 200 patients completed the study
protocol. The median seizure frequencies per month with DDSF and LF were: partial
seizures (20.5, 9.0; P < 0.001), generalized tonic-clonic seizures (6.5, 2.0; P <
0.001), myoclonic seizures (58.5, 29.0; P < 0.001). Mean plasma drug levels +/-
SD (MUg/ml) with DDSF and LF were: sodium valproate (48.2 +/- 13.7, 69.1 +/-
16.3; P < 0.001), phenytoin sodium (5.0 +/- 2.4, 12.8 +/- 3.8; P < 0.001),
carbamazepine (4.5 +/- 2.0, 11.5 +/- 4.8; P < 0.001) and phenobarbitone (14.1 +/-
5.2, 25.4 +/- 12.3, P < 0.001). The incidence of treatment emergent ADRs was poor
scholastic performance (25.5%), behavioral problems and dizziness/sedation
(21.0%), somnolence/sleep disorders (19.5%). CONCLUSION: Patients treated with LF
had better seizure control and optimal therapeutic drug levels and less adverse
effects when compared to DDSF.
PMID- 28706400
TI - Hybrid Therapy versus Sequential Therapy for Eradication of Helicobacter pylori:
A Randomized Controlled Trial.
AB - OBJECTIVE: To compare the sequential therapy (ST) with the hybrid therapy (HT)
for the eradication of Helicobacter pylori. MATERIALS AND METHODS: Patients with
peptic ulcer disease and gastritis found to be H. pylori positive were randomized
to HT group who received omeprazole (20 mg bid) and amoxicillin (1 g bid) for 7
days followed by omeprazole (20 mg bid), amoxicillin (1 g bid), clarithromycin
(500 mg bid), and metronidazole (400 mg tid) for the next 7 days and ST group who
received omeprazole and amoxicillin for 5 days followed by omeprazole,
clarithromycin, and metronidazole for the next 5 days. Eradication rate,
compliance, and complications were compared. RESULTS: A total of 120 patients
were included, sixty in each group. H. pylori eradication rate was significantly
higher in HT group on intention-to-treat analysis (88.3% [confidence interval
(CI) 78.3%-94.8%] vs. 73.3% [CI 61.1%-83.3%]; P = 0.037). Per-protocol analysis
showed higher eradication rate with HT (93% [CI 83.9%-93.7%] vs. 81.5% [CI 69.5%
90.2%]; P = 0.068); however, the difference was insignificant. Compliance and
side effects were similar. A complete course of HT costs $10.77, while ST costs
only $6.347. CONCLUSIONS: HT achieves significantly higher H. pylori eradication
rate than ST with comparable patient compliance and side effects but at an higher
price. However, it can be used in places where ST is ineffective.
PMID- 28706401
TI - Influence of West African Ethnicity and Gender on Beta-Cell Function and Insulin
Sensitivity in Essential Hypertensives Treated with Hydrochlorothiazide and
Hydrochlorothiazide-lisinopril Combination.
AB - OBJECTIVE: To assess the effects of hydrochlorothiazide (HCT) given alone and in
combination with an angiotensin-converting enzyme inhibitor (ACEI) on beta-cell
function in a negroid population to further explore possible ethnic differences
in the effect of antihypertensive drugs on homeostasis model assessment - insulin
resistance (HOMA-IR). MATERIALS AND METHODS: A total of 80 newly diagnosed
Nigerian essential hypertensive patients were assigned to receive either HCT 25
mg daily or both HCT and lisinopril (Lis; 25/10 mg daily) in an open-label study
for 12 weeks. The treatment groups were well matched in clinical and demographic
baseline features. Changes in HOMA-IR from baseline to end of study (week 12),
fasting plasma glucose (FPG), serum potassium, serum insulin, and blood pressure
over the same period were also evaluated. RESULTS: After 12 weeks, mean delta
HOMA-IR (and %) was higher in the HCT monotherapy group; although, this change
did not reach statistical significance in both groups -0.1 +/- 7.1, P = 0.538
(HCT) and 0.6 +/- 4.2 P = 0.913 (HCT + Lis); an insignificant increase was
observed in FPG and serum insulin in both groups, whereas serum potassium
decreased in similar fashion. Blood pressure reduction was similar in both
groups. Analysis of HOMA-IR change according to gender in response to HCT mono-
or combination therapy with Lis showed no significant difference. CONCLUSIONS:
HCT monotherapy in hypertensive indigenous Nigerians, was not associated with
worse metabolic effects when compared with combination therapy using Lis, an ACEI
after 12 weeks. Low-dose thiazide diuretic as first-line antihypertensive
medication may be safe in the short-term, further larger and long-term studies
are needed to corroborate this finding.
PMID- 28706402
TI - Levocetirizine-induced Psychiatric Disorders in a Pediatric Patient: A Case
Report and a Pharmacovigilance Database Analysis.
PMID- 28706403
TI - Dalbavancin Use for the Treatment of Methicillin-resistant Staphylococcus aureus
Pneumonia.
AB - Dalbavancin is a lipoglycopeptide with a long half-life that allows infrequent
dosing. It is indicated for the treatment of acute bacterial skin and skin
structure infections caused by susceptible organisms, including Staphylococcus
aureus and methicillin-resistant S. aureus (MRSA). Although this agent has been
used off-label clinically, there are minimal data in infections outside the
current indications. We report a case of a 28-year-old nonadherent male with HIV
presenting with pneumonia due to MRSA that was treated with dalbavancin. The
patient was admitted to the hospital with classic pneumonia symptoms, and sputum
cultures and bronchoalveolar lavage grew MRSA. Other infections were ruled out.
The patient was initially treated with vancomycin, but subtherapeutic
concentrations prompted a change to dalbavancin upon discharge. The patient was
readmitted 11 days later with the complaints of hemoptysis and shortness of
breath, with unchanged imaging. However, no evidence of MRSA was found at this
time. Utility of dalbavancin for other disease states has profound implications,
particularly in patients with poor medication adherence.
PMID- 28706404
TI - Dry Eye Syndrome in Menopause and Perimenopausal Age Group.
AB - Dry eye disease (DED) is a multifactorial ocular surface disease that causes
symptoms of ocular pain, discomfort, and decreased visual acuity. It
significantly affects quality of life of patients. It is more prevalent in the
females and is being specifically in the menopausal and postmenopausal age group.
This is believed to be due to the changes in balance of sex hormones. Sex
hormones - estrogens and androgens - influence production of all components of
the tear film including aqueous layer, lipid, and mucin. Various mechanisms such
as decrease in hormonal levels, shift in feedback mechanisms, and changes in
receptor receptivity interplay to alter the ocular surface homeostasis and
subsequently result in DED. Several studies have suggested potential role of
hormone replacement therapy in menopause-associated dry eye symptoms. The purpose
of this review is to help the non ophthalmic physicians about DED encountered
commonly in menopausal age group. It is important for primary care physicians to
understand DED due to its high prevalence, often debilitating symptoms and the
potentially preventable and treatable nature of the condition.
PMID- 28706405
TI - Vulvar Lichen Sclerosus et Atrophicus.
AB - Vulvar lichen sclerosus (VLS) is a chronic inflammatory dermatosis characterized
by ivory-white plaques or patches with glistening surface commonly affecting the
vulva and anus. Common symptoms are irritation, soreness, dyspareunia, dysuria,
and urinary or fecal incontinence. Anogenital lichen sclerosus (LS) is
characterized by porcelain-white atrophic plaques, which may become confluent
extending around the vulval and perianal skin in a figure of eight configuration.
Thinning and shrinkage of the genital area make coitus, urination, and defecation
painful. LS is not uncommon in India and present as an itchy vulvar dermatosis
which a gynecologist may mistake for candidal vulvovaginitis. There is often a
delay in diagnosis of VLS due to its asymptomatic nature and lack of awareness in
patients as well as physicians. Embarrassment of patients due to private nature
of the disease and failure to examine the genital skin properly are the other
reasons for delay in diagnosis. There is no curative treatment for LS. Various
medications available only relieve the symptoms. Chronic nature of the disease
affects the quality of life. Proper and regular follow-up is required as there
are chances of the development of squamous cell carcinoma.
PMID- 28706406
TI - Health-related Factors Associated with Adherence to Breast Cancer Screening.
AB - INTRODUCTION: In Belgium, an effective preventive program for breast cancer
exists but as in many countries to few women participates in the screening. This
study aims to describe the factors that affect the participation in the national
breast cancer screening program. METHODS: The participants were aged between 50
and 69 years and were recruited during an exhibition at the Brussels Exhibition
Centre. Medical history and health-related parameters of the participants were
recorded. RESULTS: In total, 350 women aged between 50 and 69 years participated.
After adjustment for age and region, 81.5% of the participants had a mammography
during the past 2 years. The multivariate analysis confirms the association
between not having had a mammography and (a) having an older age (odds ratio
[OR]: 0.25-0.87), (b) having diabetes (OR: 0.08-0.80), (c) having a family
history of coronary heart disease (OR: 0.16-0.80), (d) not following a
cholesterol diet or treatment (OR: 0.10-0.91) and (e) having a higher body mass
index (OR: 0.39-0.97). Having had a mammogram was associated with adherence to
cervical smear screening (OR: 2.74-11.21). CONCLUSIONS: Most of these
associations are most likely related to socioeconomic status. However, the
relationship with diabetes offers opportunities to increase the participation in
breast cancer screening programs because these patients have regular contacts
with their family physicians.
PMID- 28706407
TI - Incidence of Oral Lichen Planus in Perimenopausal Women: A Cross-sectional Study
in Western Uttar Pradesh Population.
AB - BACKGROUND: Hormonal fluctuations during menopause lead to endocrine changes in
women, especially in their sex steroid hormone production. Studies have
documented the role of estrogen and progesterone (Pg) on autoimmune disorders
such as multiple sclerosis, systemic lupus erythematosus, and rheumatoid
arthritis. Lichen planus (LP), an autoimmune disorder, seen frequently in
perimenopausal women, may also get affected by sex steroid hormones, but no
direct relationship has been established yet. AIM: The aim of this study is to
find the incidence of oral LP (OLP) in perimenopausal women and evaluate the
factors associated with it. MATERIALS AND METHODS: This cross-sectional study was
conducted over a period of 1 year. All the perimenopausal women (44.69 +/- 3.79
years) who came to the dental outpatient department were evaluated for the
presence of LP and various factors associated with it. Depression Anxiety Stress
Scale-21 questionnaire was used for psychometric evaluation of perimenopausal
women. RESULTS: According to our study, incidence of LP in postmenopausal women
was 10.91%, which is higher than incidence of LP in general population, i.e.,
0.5% to 2.0%. Incidence of LP increased with the severity of depression in
perimenopausal women (P = 0.000). CONCLUSION: The incidence of OLP is higher in
perimenopausal women than in general population and increases significantly with
increase in the severity of depression. LP in perimenopausal women can be
mediated by declined level of estrogen and Pg directly or indirectly through
causing depression that can trigger LP.
PMID- 28706408
TI - Factors Affecting Quality of Life in Breast Cancer Patients: A Descriptive and
Cross-sectional Study with Review of Literature.
AB - OBJECTIVE: This descriptive and cross-sectional study was undertaken to determine
the factors affecting quality of life (QOL) in breast cancer patients. METHODS:
We collected data from 60 patients of carcinoma breast post modified radical
mastectomy on radiotherapy in a tertiary care hospital. We included volunteered
patients with a signed informed consent and at least 70 Karnofsky Performance
Scale points. The data was gathered by interview technique using EORTC QLQ-C30
and QLQ-BR23 (Breast Cancer Module). RESULTS: The mean age at presentation was
47.6 years (range 30-75 years).75% patients were of low socio-economic status and
63.3% belonged to rural areas. Younger Women in the age group of 30-39 years had
faired worst on physical, social and emotional scores as compared to older women
in the age group of 70-79 years. Other factors which affected Quality of Life of
patients during treatment were stage of disease at presentation, performance
score of the patients, socioeconomic status of disease at follow up. CONCLUSION:
Age, Education status, Performance Score, Stage of disease at presentation and
status of disease at last follow up are few factors which significantly affects
QOL in Carcinoma breast patients though the treatment remains same. Advanced
studies on individual quality of life factors affecting cancer would empower
physicians for better personal care techniques and patients for easily overcoming
the disease.
PMID- 28706409
TI - Determinants of Awareness and Practice of Breast Self Examination Among Rural
Women in Trichy, Tamil Nadu.
AB - INTRODUCTION: Breast cancer is the most common cancer among women worldwide, and
it can be detected at an early stage through self-examination which increases the
chance of survival. This study aimed to assess knowledge and practice of breast
self-examination (BSE) among females in a rural area of Trichy district.
METHODOLOGY: This community-based, cross-sectional study was carried out among a
total sample of 200 women in rural area of Trichy. The participants were
interviewed using a structured interviewer-administered questionnaire to obtain
information on their sociodemographic characteristics, awareness on breast
cancer, and knowledge, attitude, practice of BSE. Data were entered into MS Excel
and analyzed using SPSS version 20.0. Spearman correlation and Chi-square test
were used to analyze the association between the variables. RESULTS: The mean age
of the study group was 36.9 +/- 8.8 years. Eighty percent were literates. Most of
the women 178 (89%) were aware of breast cancer. Only 26% of the women were aware
of BSE. Only 18% of the females had ever checked their breast and 5% practiced it
regularly. Awareness of BSE was found to be significantly associated with age and
educational attainment. CONCLUSION: The level of knowledge and practice of BSE
among females are unacceptably low. Efforts should be made to increase level of
knowledge and practice of BSE through health education programs.
PMID- 28706410
TI - Coexisting Brenner Tumor and Endometrial Carcinoma.
AB - Brenner tumor is a rare ovarian neoplasm that is seen in women of the fifth to
sixth decade. Classified as benign, borderline, and malignant, these tumors may
be associated with estrogen production, thus altering the estrogen-progesterone
ratio. High estrogen stimulates the endometrium and this is responsible for
producing various pathologies, namely, hyperplasia, atypia, and carcinoma. Very
few case reports have been published highlighting the same. A case report is
being presented here of a coexisting Brenner tumor and well-differentiated
endometrial carcinoma in a 55-year-old nulliparous postmenopausal woman.
PMID- 28706411
TI - Toxic Shock Syndrome within 24 H of an Office Hysteroscopy.
AB - Office hysteroscopy is now a common procedure performed to look at the
endometrial cavity and is relatively free of serious complications. A 68-year-old
lady, previously fit and well, presented with abdominal pain, rigors, sweats, and
vomiting within 24 h of an outpatient hysteroscopy for postmenopausal bleeding.
She was diagnosed with streptococcal toxic shock syndrome (STSS) due to Group A
beta-hemolytic streptococci. She was managed in the Intensive Care Unit, with
inotropic and antibiotic support. She recovered eventually and was discharged
home with oral antibiotics. Toxic shock syndrome due to Streptococci is an
unusual occurrence, whose incidence has been slowly increasing over the years.
However, this appears to be the first case of STSS manifesting within 24 h
following an outpatient hysteroscopy.
PMID- 28706412
TI - Uterine Adenofibroma: An Unsual Cause of Nonpuerperal Uterine Inversion in
Postmenopausal Female.
AB - Uterine adenofibroma is an extremely rare benign mixed mullerian tumor, most
often presenting as vaginal mass with pain and abnormal uterine bleeding in
postmenopausal females. Nonpuerperal uterine inversion is also an uncommon
entity. We present a rare case of nonpuerperal uterine inversion due to a uterine
adenofibroma. A 56-year-old postmenopausal female presented to us with bleeding
and discharge per vaginum. Examination showed a polyp. Due to associated
comorbidities, polypectomy was chosen as management modality failing which
laparotomy was done, and the uterus was found to be inverted through the cervix,
hysterectomy was done. Histopathological evaluation showed uterine adenofibroma.
This is the first case of inversion reported due to uterine adenofibroma.
PMID- 28706413
TI - Virilization in a Postmenopausal Female Due to Androgen Secreting Ovarian Dermoid
Cyst.
AB - Virilizing ovarian dermoid cysts are very rare. The source of androgen in these
cysts may be tumors such as Sertoli-Leydig cell tumor or Leydig cell hyperplasia.
A 52-year-old postmenopausal female with virilization was found to have an
ovarian dermoid cyst on ultrasound. Her serum testosterone levels were elevated.
Leydig cell hyperplasia within the dermoid cyst was found to be the source of
androgen in this patient.
PMID- 28706414
TI - Risk of hepatitis B reactivation in patients treated with direct-acting
antivirals for hepatitis C.
AB - The recent introduction of direct-acting antiviral drugs (DAAs) for treatment of
the hepatitis C virus (HCV) has greatly improved the management of HCV for
infected patients. These viral protein inhibitors act rapidly, allowing HCV
clearance and increasing the sustained virological response rates. However,
hepatitis B virus (HBV) reactivation has been reported in HCV/HBV co-infected
patients. Hepatitis B reactivation refers to an abrupt increase in the HBV and is
well-documented in patients with previously undetected HBV DNA due to inactive or
resolved HBV infection. Reactivation can occur spontaneously, but in most cases,
it is triggered by various factors. Reactivation can be transient, without
clinical symptoms; however, it usually causes a hepatitis flare. HBV reactivation
may occur regardless of HCV genotype and type of DAA regimen. HBV screening is
strongly recommended for co-infected HCV/HBV patients before initiation and
during DAA therapy regardless of HBV status, HCV genotype and class of DAAs used.
HBV reactivation can be prevented with pretreatment screening and prophylactic
treatment when necessary. Additional data are required to evaluate the underlying
mechanisms of HBV reactivation in this setting.
PMID- 28706415
TI - Role of new endoscopic techniques in inflammatory bowel disease management: Has
the change come?
AB - Despite significant therapeutic progress in recent years, inflammatory bowel
disease (IBD), which includes Crohn's disease and ulcerative colitis, remains a
challenge regarding its pathogenesis and long-term complications. New concepts
have emerged in the management of this disease, such as the "treat-to-target"
concept, in which mucosal healing plays a key role in the evolution of IBD, the
risk of recurrence and the need for surgery. Endoscopy is essential for the
assessment of mucosal inflammation and plays a pivotal role in the analysis of
mucosal healing in patients with IBD. Endoscopy is also essential in the
detection of dysplasia and in the identification of the risk of colon cancer. The
current surveillance strategy for dysplasia in IBD patients indicates white-light
endoscopy with non-targeted biopsies. The new chromoendoscopy techniques provide
substantial benefits for both clinicians and patients. Narrow-band imaging (NBI)
has similar rates of dysplastic lesion detection as white-light endoscopy, and it
seems that NBI identifies more adenoma-like lesions. Because it is used
instinctively by many endoscopists, the combination of these two techniques might
improve the rate of dysplasia detection. Flexible spectral imaging color
enhancement can help differentiate dysplastic and non-dysplastic lesions and can
also predict the risk of recurrence, which allows us to modulate the treatment to
gain better control of the disease. The combination of non-invasive serum and
stool biomarkers with endoscopy will improve the monitoring and limit the
evolution of IBD because it enables the use of a personalized approach to each
patient based on that patient's history and risk factors.
PMID- 28706416
TI - Implication of the Hedgehog pathway in hepatocellular carcinoma.
AB - The prognosis for patients who are diagnosed with advanced stage hepatocellular
carcinoma (HCC) is poor because there are few treatment options. Recent research
has focused on the identification of novel molecular entities that can be
targeted to inhibit oncogenic signals that are involved in the carcinogenesis,
proliferation and progression of HCC. Among all of the pathways that are involved
in the development of HCC, Hedgehog (HH) signalling has demonstrated a
substantial role in hepatocarcinogenesis and HCC progression. HH plays a
physiological role in embryogenesis, through the induction of the differentiation
of hepatocytes from endodermal progenitors. The re-activation of the HH pathway
in chronic damaged liver is a mechanism of fibrotic degeneration and is
implicated in various stages of HCC development. HH activation sustains the sub
population of immature liver epithelial cells that are involved in the
pathogenesis of cirrhosis and HCC, and HH itself is a mediator of the alcohol
derived malignant transformation of liver cells. High levels of expression of HH
protein markers in liver tumour tissues are correlated with aggressive
histological and biological features and a poor clinical outcome. In vitro and in
vivo inhibition models of the HH pathway confirm that HH is essential in
maintaining tumour growth, metastasis and a mesenchymal phenotype.
PMID- 28706417
TI - Indole phytoalexin derivatives induce mitochondrial-mediated apoptosis in human
colorectal carcinoma cells.
AB - AIM: To investigate the mechanism of the antiproliferative effect of synthetic
indole phytoalexin derivatives on human colorectal cancer cell lines. METHODS:
Changes in cell proliferation and the cytotoxic effect of the tested compounds on
human colorectal cancer cell lines and human fibroblasts were evaluated using MTS
and BrdU assay, allowing us to choose the most potent substance. Cell cycle
alterations were analyzed using flow cytometric analysis. The apoptosis-inducing
effect of compound K-453 on the HCT116 cell line was examined with annexin V/PI
double staining using flow cytometry, as well as acridine orange/propidium iodide
(AO/PI) staining. The flow cytometry method also allowed us to measure changes in
levels or activation states of other factors associated with apoptosis, such as
poly (ADP-ribose) polymerase (PARP), caspase-3 and -9, cytochrome c, Bcl-2 family
proteins, and also the integrity of the mitochondrial membrane. To evaluate
activity of the transcription factors and proteins involved in signaling pathways
we used Western blot analysis together with flow cytometry. RESULTS: Among the
ten tested compounds, compound K-453 {(+/-)-trans-1,2-dimethoxy-2'-(3,5-bis
trifluoromethylphenylamino)spiro{indoline-3,5'[4',5']dihydrothiazol} exhibited
the most potent activity with IC50 = 32.22 +/- 1.14 MUmol/L in human colorectal
HCT116 cells and was thus selected for further studies. Flow cytometric analysis
revealed a K-453-induced increase in the population of cells with sub-G1 DNA
content, which is considered as a marker of apoptotic cell death. The apoptosis
inducing effect of compound K453 was also confirmed by annexin V/PI double
staining and AO/PI staining. The apoptosis was associated with the loss of
mitochondrial membrane potential, PARP cleavage, caspase-3 and caspase-9
activation, release of cytochrome c, as well as changes in the levels of Bcl-2
family members. Moreover, flow cytometry showed that compound K-453 stimulates
phosphorylation of p38 MAPK but decreases phosphorylation of Akt and Erk 1/2.
Activation of p38 MAPK was also confirmed using Western blot analysis. This
analysis also revealed down-regulation of NF-kappaB1 (p50) and RelA (p65)
proteins and the loss of their anti-apoptotic activity. CONCLUSION: In our study
compound K-453 exhibited an antiproliferative effect by induction of intrinsic
apoptosis as well as modulation of several signaling pathways.
PMID- 28706418
TI - Naringenin prevents experimental liver fibrosis by blocking TGFbeta-Smad3 and JNK
Smad3 pathways.
AB - AIM: To study the molecular mechanisms involved in the hepatoprotective effects
of naringenin (NAR) on carbon tetrachloride (CCl4)-induced liver fibrosis.
METHODS: Thirty-two male Wistar rats (120-150 g) were randomly divided into four
groups: (1) a control group (n = 8) that received 0.7% carboxy methyl-cellulose
(NAR vehicle) 1 mL/daily p.o.; (2) a CCl4 group (n = 8) that received 400 mg of
CCl4/kg body weight i.p. 3 times a week for 8 wk; (3) a CCl4 + NAR (n = 8) group
that received 400 mg of CCl4/kg body weight i.p. 3 times a week for 8 wk and 100
mg of NAR/kg body weight daily for 8 wk p.o.; and (4) an NAR group (n = 8) that
received 100 mg of NAR/kg body weight daily for 8 wk p.o. After the experimental
period, animals were sacrificed under ketamine and xylazine anesthesia. Liver
damage markers such as alanine aminotransferase (ALT), alkaline phosphatase (AP),
gamma-glutamyl transpeptidase (gamma-GTP), reduced glutathione (GSH), glycogen
content, lipid peroxidation (LPO) and collagen content were measured. The
enzymatic activity of glutathione peroxidase (GPx) was assessed. Liver
histopathology was performed utilizing Masson's trichrome and hematoxylin-eosin
stains. Zymography assays for MMP-9 and MMP-2 were carried out. Hepatic TGF-beta,
alpha-SMA, CTGF, Col-I, MMP-13, NF-kappaB, IL-1, IL-10, Smad7, Smad3, pSmad3 and
pJNK proteins were detected via western blot. RESULTS: NAR administration
prevented increases in ALT, AP, gamma-GTP, and GPx enzymatic activity; depletion
of GSH and glycogen; and increases in LPO and collagen produced by chronic CCl4
intoxication (P < 0.05). Liver histopathology showed a decrease in collagen
deposition when rats received NAR in addition to CCl4. Although zymography assays
showed that CCl4 produced an increase in MMP-9 and MMP-2 gelatinase activity;
interestingly, NAR administration was associated with normal MMP-9 and MMP-2
activity (P < 0.05). The anti-inflammatory, antinecrotic and antifibrotic effects
of NAR may be attributed to its ability to prevent NF-kappaB activation and the
subsequent production of IL-1 and IL-10 (P < 0.05). NAR completely prevented the
increase in TGF-beta, alpha-SMA, CTGF, Col-1, and MMP-13 proteins compared with
the CCl4-treated group (P < 0.05). NAR prevented Smad3 phosphorylation in the
linker region by JNK since this flavonoid blocked this kinase (P < 0.05).
CONCLUSION: NAR prevents CCl4 induced liver inflammation, necrosis and fibrosis,
due to its antioxidant capacity as a free radical inhibitor and by inhibiting the
NF-kappaB, TGF-beta-Smad3 and JNK-Smad3 pathways.
PMID- 28706419
TI - Intestinal anti-inflammatory activity of Ground Cherry (Physalis angulata L.)
standardized CO2 phytopharmaceutical preparation.
AB - AIM: To investigate the effects of Ground Cherry (Physalis angulata L.)
standardized supercritical CO2 extract in trinitrobenzenesulphonic acid (TNBS)
model of rat intestinal inflammation. METHODS: The animals were divided into
groups that received vehicle or P. angulata extract (PACO2) orally at the doses
25, 50 and 100 mg/kg daily by 5 d before TNBS damage. Protective effects of PACO2
were assessed by macroscopic analysis, biochemical determinations of the levels
of myeloperoxidase (MPO), alkaline phosphatase (ALP), glutathione and cytokines
(such as INF-gamma, IL-1beta, IL-6, IL-10 and TNF-alpha), gene expression
evaluation (including Hsp70, heparanase, NF-kappaB, mitogen-activated protein
kinases (Mapk) 1, 3, 6 and 9, and the mucins genes Muc 1, 2, 3 and 4) and
histopathological studies using optical, and electronic (transmission and
scanning) microscopy. RESULTS: PACO2 extract promoted a significant reduction in
MPO and ALP activities, reducing oxidative stress and neutrophil infiltration.
These effects were accompanied by significant reduction of colonic levels of IFN
gamma and IL-6 and down-regulation of heparanase, Hsp70, Mapk3, Mapk9, Muc1 and
Muc2 genes expression when compared with TNBS-control animals. In addition,
protective effects were also evidenced by reduced neutrophil infiltration,
recovery of cell architecture and replacement of mucin by histopathological and
ultrastructural analysis. CONCLUSION: Physalis angulata supercritical CO2 extract
is an intestinal anti-inflammatory product that modulates oxidative stress,
immune response and expression of inflammatory mediators, with potentially
utility for treating inflammatory bowel disease.
PMID- 28706420
TI - Maytenus erythroxylon Reissek (Celastraceae) ethanol extract presents
antidiarrheal activity via antimotility and antisecretory mechanisms.
AB - AIM: To investigate the acute toxicity, phytochemical profile, antidiarrheal
activity and mechanisms of action of Maytenus erythroxylon (M. erythroxylon)
ethanol extract. METHODS: A castor oil-induced diarrhea model was used to
evaluate antidiarrheal activity. Intestinal transit and gastric emptying
protocols were used to evaluate a possible antimotility effect. KATP channels,
nitric oxide, presynaptic alpha2-adrenergic and tissue adrenergic receptors were
investigated to uncover antimotility mechanisms of action and castor oil-induced
enteropooling to elucidate antisecretory mechanisms. RESULTS: All tested doses of
the extract (62.5, 125, 250 and 500 mg/kg) possessed antidiarrheal activity, with
a significant decrease of the evacuation index. This activity is possibly related
to a reduced gastric emptying (125, 250 and 500 mg/kg) and to a decreased
percentage of intestinal transit for all tested doses. That last effect seems to
be modulated by nitric oxide, KATP channels and tissue adrenergic receptors.
Besides, the extract also presented antisecretory effect due to a decrease of
intestinal fluid accumulation. CONCLUSION: The antidiarrheal effect of M.
erythroxylon found in this study involves antimotility and antisecretory
mechanisms that may be attributed to the chemical compounds found in this
species: saponins, flavonoids, tannins, triterpenes and steroids.
PMID- 28706421
TI - Gastric cancer-derived heat shock protein-gp96 peptide complex enhances dendritic
cell activation.
AB - AIM: To investigate the role of heat shock protein (HSP)-glycoprotein (gp)96 in
dendritic cells (DCs) and lymphocytes induction in gastric cancer (GC). METHODS:
Human GC cell lines KATOIII, MKN-28 and SGC-7901 were infected with adenovirus
gp96 at a multiplicity of infection of 100. gp96-GC antigen peptide complexes
were purified. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide)
assay, lactate dehydrogenase (LDH) release assay and enzyme-linked immunosorbent
assay were used to determine allo-reactive T cell stimulation, natural killer
(NK) cell activity and expression of cytokines (such as interleukin (IL)-10, IL
12, interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha), respectively.
Effect of cytotoxic T lymphocyte (CTL) on DCs incubated with HSP-gp96 was also
evaluated by LDH release. All assays were performed in triplicate and the average
values were reported. Comparison between groups was conducted using Student's t
test. RESULTS: T cells incubated with HSP-gp96 exhibited a marked increase in
proliferation in a dose-dependent manner (P < 0.05). NK cell activity after gp96
GC peptide complex treatment was significantly higher than that after antigen
peptide treatment (P < 0.05). The activity of CTLs incubated with DCs from three
GC cells lines was obviously higher than that stimulated by GC antigen at ratios
of 50: 1, 25: 1, 10: 1, and 5: 1 (P < 0.05). Furthermore, the secretion of TNF
alpha, IL-10, IL-12 (P70) and IFN-gamma markedly increased after incubation with
HSP-gp96 (P < 0.05). CONCLUSION: HSP-gp96 promotes T cell response, enhances DC
antigen presentation and induces cytokine secretion, as well. HSP-gp96 has
potential as immunotherapy for elimination of residual GC cells.
PMID- 28706422
TI - Para-aortic node involvement is not an independent predictor of survival after
resection for pancreatic cancer.
AB - AIM: To analyze the importance of para-aortic node status in a series of patients
who underwent pancreaticoduodenectomy (PD) in a single Institution. METHODS:
Between January 2000 and December 2012, 151 patients underwent PD with para
aortic node dissection for pancreatic adenocarcinoma in our Institution. Patients
were divided into two groups: patients with negative PALNs (PALNs-), and patients
with metastatic PALNs (PALNs+). Pathologic factors, including stage, nodal
status, number of positive nodes and lymph node ratio, invasion of para-aortic
nodes, tumor's grading, and radicality of resection were studied by univariate
and multivariate analysis. Survival curves were constructed with Kaplan-Meier
method and compared with Log-rank test: significance was considered as P < 0.05.
RESULTS: A total of 107 patients (74%) had nodal metastases. Median number of
pathologically assessed lymph nodes was 26 (range 14-63). Twenty-five patients
(16.5%) had para-aortic lymph node involvement. Thirty-three patients (23%)
underwent R1 pancreatic resection. One-hundred forty-one patients recurred and
died for tumor recurrence, one is alive with recurrence, and 9 are alive and free
of disease. Overall survival was significantly influenced by grading (P =
0.0001), radicality of resection (P = 0.001), stage (P = 0.03), lymph node status
(P = 0.04), para-aortic nodes metastases (P = 0.02). Multivariate analysis showed
that grading was an independent prognostic factor for overall survival (P =
0.0001), while grading (P = 0.0001) and radicality of resection (P = 0.01) were
prognostic parameters for disease-free survival. Number of metastatic nodes, node
ratio, and para-aortic nodes involvement were not independent predictors of
disease-free and overall survival. CONCLUSION: In this experience, lymph node
status and para-aortic node metastases were associated with poor survival at
univariate analysis, but they were not independent prognostic factors.
PMID- 28706423
TI - Risk factors for metachronous gastric carcinoma development after endoscopic
resection of gastric dysplasia: Retrospective, single-center study.
AB - AIM: To determine the gastric adenocarcinoma (GAC) occurrence rate and related
factors, we evaluated the follow-up results of patients confirmed to have gastric
dysplasia after endoscopic resection (ER). METHODS: We retrospectively analyzed
the medical records, endoscopic examination records, endoscopic procedure
records, and histological records of 667 cases from 641 patients who were
followed-up for at least 12 mo, from among 1273 patients who were conformed to
have gastric dysplasia after Endoscopic mucosal resection (EMR) or endoscopic
submucosal dissection (ESD) of gastric mucosal lesions between January 2007 and
August 2013 at the Chungnam National University Hospital. RESULTS: The mean
follow-up period was 33.8 mo, and the median follow-up period was 29 mo (range:
12-87). During the follow-up period, the occurrence of metachronous GAC was 4.0%
(27/667). The mean and median interval periods between the occurrence of
metachronous GAC and endoscopic treatment of gastric dysplasia were 36.3 and 34
mo, respectively (range: 16-71). The factors related to metachronous GAC
occurrence after ER for gastric dysplasia were male sex (5.3% vs 1.0%), open-type
atrophic gastritis (9.5% vs 3.4%), intestinal metaplasia (6.8% vs 2.4%), and high
grade dysplasia (HGD; 8.4% vs 3.2%). Among them, male sex [OR: 5.05 (1.18-21.68),
P = 0.029], intestinal metaplasia [OR: 2.78 (1.24-6.23), P = 0.013], and HGD [OR:
2.70 (1.16-6.26), P = 0.021] were independent related factors in multivariate
analysis. Furthermore, 24 of 27 GAC cases (88.9%) occurred at sites other than
the previous resection sites, and 3 (11.1%) occurred at the same site as the
previous resection site. CONCLUSION: Male sex, intestinal metaplasia, and HGD
were significantly related to the occurrence of metachronous GAC after ER of
gastric dysplasia, and most GACs occurred at sites other than the previous
resection sites.
PMID- 28706424
TI - New magnifying endoscopic classification for superficial esophageal squamous cell
carcinoma.
AB - AIM: To assess the accuracy of a new magnifying endoscopy (ME) classification for
predicting depth of invasion of superficial esophageal squamous cell carcinoma
(SESCC). METHODS: This study included a total of 70 lesions in 69 patients with
SESCC who underwent ME with narrow-band imaging (ME-NBI) before resection from
August 2010 to July 2016. Accuracy of ME-NBI for predicting depth of invasion of
SESCC was analyzed by using a new ME classification proposed by the Japan
Esophageal Society (JES), and interobserver agreement was assessed. RESULTS:
Overall accuracy of ME-NBI for estimating depth of invasion of SESCC was 78.6%.
Sensitivity and specificity of type B1 for tumors limited to the epithelial layer
(m1) or invading into the lamina propria (m2) were 71.4% and 100%, respectively.
Sensitivity and specificity of type B2 for tumors invading into the muscularis
mucosa (m3) or superficial submucosa (<= 200 MUm, sm1) were 94.4% and 73.1%,
respectively, while those of type B3 for tumors invading into the deep submucosa
(> 200 MUm, sm2) were 75.0% and 97.8%, respectively. Interobserver agreement was
excellent (kappa = 0.86, 95%CI: 0.76-0.95). CONCLUSION: The recently developed
JES ME classification is useful for predicting depth of invasion of SESCC, with
reliable interobserver agreement.
PMID- 28706425
TI - Procalcitionin as a diagnostic marker to distinguish upper and lower
gastrointestinal perforation.
AB - AIM: To assess the accuracy of serum procalcitionin (PCT) as a diagnostic marker
in verifying upper and lower gastrointestinal perforation (GIP). METHODS: This
retrospective study included 46 patients from the surgical intensive care unit
(ICU) of the Second Affiliated Hospital of Harbin Medical University who were
confirmed to have GIP between June 2013 and December 2016. Demographic and
clinical patient data were recorded on admission to ICU. Patients were divided
into upper (n = 19) and lower (n = 27) GIP groups according to the perforation
site (above or below Treitz ligament). PCT and WBC count was obtained before
laparotomy and then compared between groups. Meanwhile, the diagnostic accuracy
of PCT was analyzed. RESULTS: Patients with lower GIP exhibited significantly
higher APACHE II score, SOFA score and serum PCT level than patients with upper
GIP (P = 0.017, 0.004, and 0.001, respectively). There was a significant positive
correlation between serum PCT level and APACHE II score or SOFA score (r = 0.715
and r = 0.611, respectively), while there was a significant negative correlation
between serum PCT level and prognosis (r = -0.414). WBC count was not
significantly different between the two groups, and WBC count showed no
significant correlation with serum PCT level, APACHE II score, SOFA score or
prognosis. The area under the receiver operating characteristic curve of PCT
level to distinguish upper or lower GIP was 0.778. Patients with a serum PCT
level above 17.94 ng/dL had a high likelihood of lower GIP, with a sensitivity of
100% and a specificity of 42.1%. CONCLUSION: Serum PCT level is a reliable and
accurate diagnostic marker in identifying upper or lower GIP before laparotomy.
PMID- 28706426
TI - Healthcare utilization and costs associated with gastroparesis.
AB - AIM: To use a national database of United States hospitals to evaluate the
incidence and costs of hospital admissions associated with gastroparesis.
METHODS: We analyzed the National Inpatient Sample Database (NIS) for all
patients in whom gastroparesis (ICD-9 code: 536.3) was the principal discharge
diagnosis during the period, 1997-2013. The NIS is the largest publicly available
all-payer inpatient care database in the United States. It contains data from
approximately eight million hospital stays each year. The statistical
significance of the difference in the number of hospital discharges, length of
stay and hospital costs over the study period was determined by regression
analysis. RESULTS: In 1997, there were 3978 admissions with a principal discharge
diagnosis of gastroparesis as compared to 16460 in 2013 (P < 0.01). The mean
length of stay for gastroparesis decreased by 20 % between 1997 and 2013 from 6.4
d to 5.1 d (P < 0.001). However, during this period the mean hospital charges
increased significantly by 159 % from $13350 (after inflation adjustment) per
patient in 1997 to $34585 per patient in 2013 (P < 0.001). The aggregate charges
(i.e., "national bill") for gastroparesis increased exponentially by 1026 % from
$50456642 +/- 4662620 in 1997 to $568417666 +/- 22374060 in 2013 (P < 0.001). The
percentage of national bill for gastroparesis discharges (national bill for
gastroparesis/total national bill) has also increased over the last 16 years
(0.0013% in 1997 vs 0.004% in 2013). During the study period, women had a higher
frequency of gastroparesis discharges when compared to men (1.39/10000 vs
0.9/10000 in 1997 and 5.8/10000 vs 3/10000 in 2013). There was a 6-fold increase
in the discharge diagnosis of gastroparesis amongst type 1 DM and 3.7-fold
increase amongst type 2 DM patients over the study period (P < 0.001).
CONCLUSION: The number of inpatient admissions for gastroparesis and associated
costs have increased significantly over the last 16 years. Inpatient costs
associated with gastroparesis contribute significantly to the national healthcare
bill. Further research on cost-effective evaluation and management of
gastroparesis is required.
PMID- 28706427
TI - Variability of anti-human transglutaminase testing in celiac disease across
Mediterranean countries.
AB - AIM: To verify the precision and accuracy of transglutaminase antibodies (TGA)
assays across Mediterranean countries. METHODS: This study involved 8 referral
centres for celiac disease (CD) in 7 Mediterranean countries. A central
laboratory prepared 8 kits of 7 blinded and randomized serum samples, with a
titrated amount of Human TGA IgA. Each sample was analysed three times on three
different days, with each centre running a total of 21 tests. The results were
included in a blindly coded report form, which was sent to the coordinator
centre. The coordinator estimated the mean coefficient of Variation (CoVar =
sigma/MU), the mean accuracy (Accur = Vobserved - Vreal) and the mean percent
variation (Var% = [(Vobserved - Vreal)/Vreal] * 100). RESULTS: The analysis
showed that 79.17% of the mean variation fell between -25% and +25% of the
expected value, with the accuracy and precision progressively increasing with
higher titres of TGA. From values 1.25 times greater than the normal cut-off, the
measurements were highly reliable. CONCLUSION: TGA estimation is a crucial step
for the diagnosis of CD; given its accuracy and precision, clinicians could be
confident in establishing a diagnosis.
PMID- 28706428
TI - Appropriateness of the study of iron deficiency anemia prior to referral for
small bowel evaluation at a tertiary center.
AB - AIM: To evaluate the adequacy of the study of iron deficiency anemia (IDA) in
real life practice prior to referral to a gastroenterology department for small
bowel evaluation. METHODS: All consecutive patients referred to a
gastroenterology department for small bowel investigation due to iron deficiency
anemia, between January 2013 and December 2015 were included. Both patients
referred from general practitioners or directly from different hospital
departments were selected. Relevant clinical information regarding prior anemia
workup was retrospectively collected from medical records. An appropriate pre
referral study was considered the execution of esophagogastroduodenoscopy (EGD)
with Helicobacter pylori (H. pylori) investigation, colonoscopy with quality
standards (recent, total and with adequate preparation) and celiac disease (CD)
screening (through serologic testing and/or histopathological investigation).
RESULTS: A total of 77 patients (58.4% female, mean age 67.1 +/- 16.7 years) were
included. Most (53.2%) patients were referred from general practitioners, 41.6%
from other hospital specialties and 5.2% directly from the emergency department.
The mean pre-referral hemoglobin concentration was 8.8 +/- 2.0 g/dL and the
majority of anemias had microcytic (71.4%) and hypochromic (72.7%)
characteristics. 77.9% of patients presented with an incomplete pre-referral
study: EGD in 97.4%, with H. pylori investigation in 58.3%, colonoscopy with
quality criteria in 63.6%, and CD screening in 24.7%. Patients with an
appropriate study at the time of referral were younger (48.7 +/- 17.7 vs 72.3 +/-
12.3 years, P < 0.001). Small bowel evaluation was ultimately undertaken in 72.7%
of patients, with a more frequent evaluation in patients with a quality
colonoscopy at referral (78.6% vs 23.8%); P < 0.001 (OR = 11.7, 95%CI: 3.6-38.6).
The most common diagnosis regarded as the likely cause of IDA was small bowel
angioectasia (18.2%) but additional causes were also found in the upper and lower
gastrointestinal tracts of near 20% of patients. Small bowel studies detected
previously unknown non-small bowel findings in 7.7% of patients. CONCLUSION: The
study of anemia prior to referral to gastroenterology department is
unsatisfactory. Only approximately a quarter of patients presented with an
appropriate study.
PMID- 28706429
TI - Comparing reduced-dose sodium phosphate tablets to 2 L of polyethylene glycol: A
randomized study.
AB - AIM: To compare the tolerability and quality of bowel cleansing between 2 L
polyethylene glycol (PEG) and reduced-dose sodium phosphate (NaP) tablets as a
preparation for colonoscopy. METHODS: Two hundred patients were randomly assigned
to the PEG or NaP groups at the same ratio. The NaP group patients took 30
tablets with 2 L of clear liquid, while the PEG group patients took 2L of PEG.
Tolerability was assessed by a questionnaire about taste, volume, and the overall
impression. The bowel cleansing quality was evaluated by colonoscopists. RESULTS:
Although NaP showed better tolerability in terms of taste, volume and overall
impression (P < 0.01, P < 0.01 and P = 0.02, respectively), the overall cleansing
quality was better in the PEG group (P < 0.01). A subgroup analysis, stratified
by sex and age, indicated that NaP was associated with better tolerability and
equivalent bowel cleansing quality in females of < 50 years of age. CONCLUSION:
Despite the better tolerability, the use of 30 NaP tablets with 2 L of clear
liquid should be limited due to its lower cleansing quality; however, in certain
cases the regimen may deserve consideration, particularly in cases involving
young women.
PMID- 28706430
TI - Case of pediatric traditional serrated adenoma resected via endoscopic submucosal
dissection.
AB - Traditional serrated adenoma (TSA) is a type of serrated polyp of the colorectum
and is thought to be a precancerous lesion. There are three types of serrated
polyps, namely, hyperplastic polyps, sessile serrated adenomas/polyps, and TSAs.
TSA is the least common of the three types and accounts for about 5% of serrated
polyps. Here we report a pediatric case of TSA that was successfully resected by
endoscopic submucosal dissection (ESD). This rare case report describes a
pediatric patient with no family history of colonic polyp who was admitted to our
hospital with hematochezia. On colonoscopy, we found a polypoid lesion measuring
10 mm in diameter in the lower rectum. We selected ESD as a surgical option for
en bloc resection, and histopathological examination revealed TSA. The findings
in this case suggest that TSA with precancerous potential can occur in children,
and that ESD is useful for treating this lesion.
PMID- 28706431
TI - Pancreatic T/histiocyte-rich large B-cell lymphoma: A case report and review of
literature.
AB - Primary pancreatic lymphoma (PPL) is an extremely rare form of extranodal
malignant lymphoma. The most common histological subtype of PPL is diffuse large
B cell lymphoma (DLBCL). In rare cases, PPL can also present as follicular
lymphoma, small lymphocytic lymphoma, and T cell lymphoma either of non-Hodgkin's
lymphoma or of Hodgkin's lymphoma. T-cell/histiocyte-rich large B-cell lymphoma
(T/HRBCL) is an uncommon morphologic variant of DLBCL with aggressive clinical
course, it is predominantly a nodal disease, but extranodal sites such as bone
marrow, liver, and spleen can be involved. Pancreatic involvement of T/HRBCL was
not presented before. Herein, we report a 48-year-old male who was hospitalized
with complaints of jaundice, dark brown urine, pale stools, and nausea. The
radiological evaluation revealed a pancreatic head mass and, following operative
biopsy, the tumor was diagnosed as T/HRBCL. The patient achieved remission after
six cycles of CHOP chemotherapy. Therefore, T/HRBCL can be treated similarly to
the stage-matched DLBCL and both of them get equivalent outcomes after
chemotherapy.
PMID- 28706432
TI - Rigor, Transparency, and Reporting Social Science Research: Why Guidelines Don't
Have to Kill Your Story.
AB - Dissemination of research is the most challenging aspect of building the evidence
base. Despite peer-review, evidence suggests that a substantial proportion of
papers leave out details that are necessary to judge bias, consider replication,
or initiate meta-analyses and systematic reviews. Reporting guidelines were
created to ensure minimally adequate reporting of research and have become
increasingly popular since the 1990s. There are over 200 guidelines for authors
to assist in reporting a range of study methodologies. Although guidelines are
freely available, they are underutilized and there is criticism regarding
assumptions about methodologies targeted by guidelines. As journal editors lean
into endorsements, social work authors may benefit from considering guidelines
appropriate for their work. This paper explores pros and cons of guideline use by
authors and journals and presents some suggestions for the field of social work,
including assessment of whether profession-specific reporting guidelines are
needed, and cautions regarding limitations.
PMID- 28706433
TI - End-of-Kindergarten Spelling Outcomes: How Can Spelling Error Analysis Data
Inform Beginning Reading Instruction?
AB - In this article, the authors examined the spelling performance of 430
kindergarteners, which included a high risk sample, to determine the relations
between end of kindergarten reading and spelling in a high quality language arts
setting. The spelling outcomes including the spelling errors between the good and
the poor readers were described, analyzed, and compared. The findings suggest
that not all the children have acquired the desired standard as outlined by the
Common Core State Standards. In addition, not every good reader is a good speller
and that not every poor speller is a poor reader. The study shows that spelling
tasks that are accompanied by spelling errors analysis provide a powerful window
for making instructional sense of children's spelling errors and for
individualizing spelling instructional strategies.
PMID- 28706434
TI - Does Model Matter? Examining Change Across Time for Youth in Group Homes.
AB - Group homes are a frequently used but controversial treatment setting for youth
with mental health problems. Within the relatively sparse literature on group
homes, there is some evidence that some models of treatment may be associated
with more positive outcomes for youth. This article explores this possibility by
examining differences across time for youth served in group homes utilizing the
Teaching Family Model (TFM) and geographically proximate homes using more
eclectic approaches. Data come from a longitudinal quasi-experimental study that
included 554 youth. Results suggest that youth showed, on average, significant
and rapid improvement during initial months in a group home. Improvement did not
differ for TFM and non-TFM homes during this initial period. Post-discharge
results, though, show that TFM was associated with continued improvement after
discharge and significantly better outcomes by 8 months post-discharge. Results
also discuss youth-level factors that may influence outcomes as well as need for
additional work to more fully understand processes and practices that are key for
maximizing and maintaining youths' positive outcomes during and after group home
placements.
PMID- 28706435
TI - Genome-Wide Polygenic Scores Predict Reading Performance Throughout the School
Years.
AB - It is now possible to create individual-specific genetic scores, called genome
wide polygenic scores (GPS). We used a GPS for years of education (EduYears) to
predict reading performance assessed at UK National Curriculum Key Stages 1 (age
7), 2 (age 12) and 3 (age 14) and on reading tests administered at ages 7 and 12
in a UK sample of 5,825 unrelated individuals. EduYears GPS accounts for up to 5%
of the variance in reading performance at age 14. GPS predictions remained
significant after accounting for general cognitive ability and family
socioeconomic status. Reading performance of children in the lowest and highest
12.5% of the EduYears GPS distribution differed by a mean growth in reading
ability of approximately two school years. It seems certain that polygenic scores
will be used to predict strengths and weaknesses in education.
PMID- 28706436
TI - The presence of kynurenine aminotransferases in the human cornea: Evidence from
bioinformatics analysis of gene expression and immunohistochemical staining.
AB - PURPOSE: Kynurenine aminotransferases (KATs) catalyze the synthesis of kynurenic
acid (KYNA), a compound of significant biological activity. The aim of this study
is to investigate the presence and distribution of KAT immunoreactivity in the
healthy human cornea. METHODS: Data on gene expression in human eye structures
were extracted from public microarray experiments using Genevestigator software.
Immunohistochemistry was conducted using polyclonal antibodies against KAT I, II,
and III on sections of eight enucleated eyes from patients with choroidal
melanoma. RESULTS: Bioinformatics analysis showed that all four KAT isoforms were
actively transcribed in the cornea and the conjunctiva. Immunohistochemical
analysis revealed the presence of KAT I, II, and III in all examined corneal
sections. The corneal endothelium showed the strongest reactivity for all three
KAT isoforms. There was a slight positive staining of the corneal stroma for KAT
I and II. KAT III immunoreactivity was found only in the stroma of the limbal
region. In the corneal epithelium, the expression of all three KAT isoforms
showed a specific pattern of the stain with fine squatter granules throughout the
cytoplasm. This reactivity was more pronounced in the basal cell layers. The
intermediate cell layers showed only faint immunoreactivity, and occasionally,
there was no staining. KAT I, II, and III were also present in the adjacent
limbal conjunctiva. CONCLUSIONS: The results indicate that kynurenine can be
metabolized to KYNA in the corneal epithelium, stroma, and endothelium.
PMID- 28706437
TI - Comparison of two neurotrophic serpins reveals a small fragment with cell
survival activity.
AB - PURPOSE: Protease nexin-1 (PN-1), a serpin encoded by the SERPINE2 gene, has
serine protease inhibitory activity and neurotrophic properties in the brain. PN
1 inhibits retinal angiogenesis; however, PN-1's neurotrophic capacities in the
retina have not yet been evaluated. Pigment epithelium-derived factor (PEDF) is a
serpin that exhibits neurotrophic and antiangiogenic activities but lacks
protease inhibitory properties. The aim of this study is to compare PN-1 and
PEDF. METHODS: Sequence comparisons were performed using computer bioinformatics
programs. Mouse and bovine eyes, human retina tissue, and ARPE-19 cells were used
to prepare RNA and protein samples. Interphotoreceptor matrix lavage was obtained
from bovine eyes. Gene expression and protein levels were evaluated with reverse
transcription PCR (RT-PCR) and western blotting, respectively. Recombinant human
PN-1, a version of PN-1 referred to as PN-1[R346A] lacking serine protease
inhibitory activity, and PEDF proteins were used, as well as synthetic peptides
designed from PEDF and PN-1 sequences. Survival activity in serum-starved, rat
derived retinal precursor (R28) cells was assessed with terminal deoxynucleotidyl
transferase (TdT) dUTP nick-end labeling (TUNEL) cell death assays. Bcl2 levels
were measured with RT-PCR. RESULTS: PN-1 is analogous in primary and tertiary
structure to PEDF. A region in PN-1 shares homology with the neurotrophic active
region of PEDF, a 17-residue region within alpha helix C. The native human
retina, ARPE-19 cells, and murine RPE and retina expressed the gene for PN-1
(SERPINE2 and Serpine2 mRNA). The retina, ARPE-19 cell lysates, and bovine
interphotoreceptor matrix contained PN-1 protein. The addition of PN-1, PN
1[R346A], or the 17mer peptide of PN-1 to serum-starved retina cells decreased
the number of TUNEL-positive nuclei relative to the untreated cells, such as
PEDF. PN-1, PN-1[R346A], and PN-1-17mer treatments increased the Bcl2 transcript
levels in serum-starved cells, as seen with PEDF. CONCLUSIONS: PN-1 and PEDF
share structural and functional features, and expression patterns in the retina.
These serpins' mechanisms of action as cell survival factors are independent of
serine protease inhibition. We have identified PN-1 as a novel factor for the
retina that may play a neuroprotective role in vivo, and small peptides as
relevant candidates for preventing retinal degeneration.
PMID- 28706438
TI - Genistein suppresses retinoblastoma cell viability and growth and induces
apoptosis by upregulating miR-145 and inhibiting its target ABCE1.
AB - PURPOSE: Retinoblastoma is a rare malignancy in developing retina tissue in
children with limited therapeutic options. Here we sought to investigate the
potential clinical value of genistein, the phytoestrogen derived from the soybean
with antioxidant activity, in this disease. METHODS: Retinoblastoma cells were
treated with genistein. Colony formation capacity was measured with soft agar
assay. MiRNA was identified with microarray. Post-transcriptional regulation of
gene expression was determined with dual-luciferase reporter assay. Cell
proliferation and apoptosis were measured with the Cell Counting Kit-8 (CCK-8)
method and annexin V-propidium iodide (PI) staining. The xenograft model was
administered with genistein, and tumor growth was monitored. RESULTS: The results
showed that genistein treatment significantly suppressed proliferation and
anchorage-independent growth of the human retinoblastoma cell line Y79 in vitro,
which partially attributed to apoptosis induction. MicroRNA array screening
identified that miR-145 was upregulated by genistein. Through post
transcriptional regulation of ABCE1, miR-145 functioned as a key downstream
effector in genistein-mediated tumor suppression in retinoblastoma. Moreover, the
in vivo data consolidated the inhibitory effect of genistein against
retinoblastoma xenograft via upregulation of miR-145. CONCLUSIONS: The data
highlighted the therapeutic potency of genistein in this disease and showed that
further clinical investigation is warranted.
PMID- 28706439
TI - Genome-wide retinal transcriptome analysis of endotoxin-induced uveitis in mice
with next-generation sequencing.
AB - PURPOSE: Endotoxin-induced uveitis (EIU) is a well-established mouse model for
studying human acute inflammatory uveitis. The purpose of this study is to
investigate the genome-wide retinal transcriptome profile of EIU. METHODS: The
anterior segment of the mice was examined with a slit-lamp, and clinical scores
were evaluated simultaneously. The histological changes in the posterior segment
of the eyes were evaluated with hematoxylin and eosin (H&E) staining. A high
throughput RNA sequencing (RNA-seq) strategy using the Illumina Hiseq 2500
platform was applied to characterize the retinal transcriptome profile from
lipopolysaccharide (LPS)-treated and untreated mice. The validation of the
differentially expressed genes (DEGs) was analyzed with real-time PCR. RESULTS:
At the 24th hour after challenge, the clinical score of the LPS group was
significantly higher (3.83+/-0.75, mean +/- standard deviation [SD]) than that of
the control group (0.08+/-0.20, mean +/- SD; p<0.001). The histological
evaluation showed a large number of inflammatory cells infiltrated into the
vitreous cavity in the LPS group compared with the control group. A total of 478
DEGs were identified with RNA-seq. Among these genes, 406 were upregulated and 72
were downregulated in the LPS group. Gene Ontology (GO) enrichment showed three
significantly enriched upregulated terms. Twenty-one upregulated and seven
downregulated pathways were remarkably enriched by Kyoto Encyclopedia of Genes
and Genomes (KEGG) pathway enrichment. Eleven inflammatory response-, complement
system-, fibrinolytic system-, and cell stress-related genes were validated to
show similar results as the RNA-seq. CONCLUSIONS: We first reported the retinal
transcriptome profile of the EIU mouse with RNA-seq. The results indicate that
the abnormal changes in the inflammatory response-, complement system-,
fibrinolytic system-, and cell stress-related genes occurred concurrently in EIU.
These genes may play an important role in the pathogenesis of EIU. This study
will lead to a better understanding of the underlying mechanisms and shed light
on discovering novel therapeutic targets for ocular inflammation.
PMID- 28706440
TI - Reliability of an Integrated Ultrasound and Stereophotogrammetric System for
Lower Limb Anatomical Characterisation.
AB - BACKGROUND: Lower extremity analysis for preoperative total knee and hip
arthroplasty routines can increase surgery success rate and hence reduce
associated costs. Current tools are limited by being invasive, limited to supine
analysis, or too expensive. This study aimed to propose and validate a device,
OrthoPilot(r), based on the combined use of a stereophotogrammetric and
ultrasound system which can in vivo and noninvasively measure varus/valgus,
flexion/extension, femur and tibia torsion, and femur and tibia lengths. METHODS:
A phantom was measured by four operators to determine the resolution of the
system. Interoperator variability was measured on three operators who measured
the above six variables on both legs of three subjects in standing and supine
positions. Intraoperator variability was assessed on data from three repeats from
9 subjects (18 legs). RESULTS: All 6 variables were reliably detected on a
phantom, with a resolution of 1 mm and 0.5 degrees . Inter- and intraoperator
consistency was observed for varus/valgus, flexion/extension, and length
measurements on the healthy subjects in standing and supine positions (all ICC >
0.93). For torsion measurements, there was a considerable variation. CONCLUSION:
The proposed system, when used on healthy subjects, allowed reliable measurements
of key parameters for preoperative procedures in both supine and standing
positions. Accuracy testing and further validation on patient populations will be
the next step toward its clinical adoption.
PMID- 28706441
TI - Ocular lubricant use in medically and surgically treated glaucoma: a
retrospective longitudinal analysis.
AB - BACKGROUND: Chronic use of intraocular pressure-lowering medications is
associated with ocular surface disease (OSD). In this study, we assess the
incidence of topical lubricant use as a surrogate marker for underlying OSD, in
medically and surgically treated glaucoma patients. METHODS: Retrospective chart
review was performed for newly diagnosed glaucoma patients who were started on
topical medications in 2007 and followed up over a 5-year period. Primary outcome
measure was the incidence of topical lubricant use in these patients and a subset
of these patients who required glaucoma or cataract surgery during follow-up.
RESULTS: Charts of 505 newly diagnosed glaucoma patients with no prior history of
ocular lubricant use were analyzed. Mean age was 63.9 years (SD 11.1), 42.8% were
women. One hundred one (20.0%) patients underwent phacoemulsification surgery, 80
underwent mitomycin C (MMC) augmented phacotrabeculectomy, 16 underwent MMC
augmented trabeculectomy and 3 underwent tube surgery during the course of follow
up as their only type of surgery. Five-year incidence of lubricant use was 59% in
all glaucoma subjects; 54.1% of patients were on medical treatment and 74.0% of
patients who underwent phacotrabeculectomy or trabeculectomy were started on
lubricants, respectively (P=0.0011); 60.4% of glaucoma subjects who underwent
phacoemulsification surgery were started on lubricants. Incidence of lubricant
use increased from 17.7% preoperatively to 74.0% postoperatively in subjects who
required trabeculectomy or phacotrabeculectomy. Incidence of lubricant use was
similar in patients on one or multiple glaucoma medications, with the mean onset
of lubricant use being 10 months after starting glaucoma medication in both
groups. Females were more likely to use artificial tears compared with males
(P=0.002). CONCLUSION: Both medical and surgical management of glaucoma have an
adverse effect on the ocular surface. Chronic use of glaucoma medications was
associated with a high incidence of ocular lubricant use. MMC-augmented
trabeculectomy was associated with an even higher incidence of ocular lubricant
use.
PMID- 28706442
TI - Topography-modified refraction: adjustment of treated cylinder amount and axis to
the topography versus standard clinical refraction in myopic topography-guided
LASIK.
PMID- 28706443
TI - Comparison of EQ-5D-5L health state utilities using four country-specific tariffs
on a breast cancer patient sample in mainland China.
AB - OBJECTIVE: The objective of this study was to compare the differences in the five
level EuroQol-5 dimensions (EQ-5D-5L) health state utility scores derived from
Chinese, Japanese, Korean, and UK tariffs. METHODS: Six hundred and twenty-one
breast cancer patients were invited for a face-to-face interview in Qingdao
Municipal Hospital, China. EQ-5D-5L was scored using tariffs from China, Japan,
Korea, and the UK. The null hypothesis of normal distribution of the EQ-5D-5L
utility score was tested by the Shapiro-Wilk test. Nonparametric Friedman test
and Wilcoxon signed-rank test were used to determine the difference among the
four tariffs. The intraclass correlation coefficients (ICCs) and Bland-Altman
plots were used to study the agreement among the four EQ-5D-5L scores. Known
groups validity was studied using a regression framework. RESULTS: There were 608
participants in the final analysis, with a mean +/- standard deviation (SD) age
of 48.0+/-9.6 years. EQ-5D-5L utility scores were non-normally distributed. The
means (median) +/- SD of EQ-5D-5L utilities derived from Chinese, Japanese,
Korean, and UK tariffs were 0.828 (0.879) +/-0.184, 0.802 (0.823) +/-0.164, 0.831
(0.829) +/-0.137, and 0.838 (0.866) +/-0.154, respectively. Among pairwise
comparisons, the difference of median EQ-5D-5L utility scores was only
insignificant between Chinese and UK tariffs. Excellent agreements (with ICCs
>0.9) were found among the four tariffs albeit the limits of agreement between
each pair of tariffs were wide. Known-groups validity was supported. CONCLUSION:
Although four country-specific EQ-5D-5L tariffs have shown an overall high level
of correlation and agreement, none of them could be regarded as interchangeable.
The higher correlation and agreement between Chinese and UK tariffs may be due to
the similar functions that were used in the tariff development. In the absence of
Chinese-specific tariff, the UK tariff is the second-best option to be applied in
the Chinese population. Results of this study further contribute to the
explanation of variations among country-specific tariffs.
PMID- 28706444
TI - Patients' conceptions of their own influence on good treatment response to
biological therapy in chronic inflammatory arthritis.
AB - BACKGROUND: Biological therapies are common in the treatment of patients with
chronic inflammatory arthritis (CIA). However, despite the fact that many
patients respond well to their biological therapies, there are still a number of
nonresponders. In order to design the best care for patients, it is important to
understand how they conceive their own role in their treatment response.
OBJECTIVE: To explore how patients with CIA conceive their own influence on a
good treatment response to biological therapy. METHODS: This study had an
exploratory and descriptive design with a phenomenographic approach. Interviews
were conducted with 25 patients (11 women and 14 men) aged 17-79 years, with CIA
who were undergoing biological therapy and who had low disease activity or were
in remission. RESULTS: Patients with CIA undergoing biological therapy conceived
their own influence on good treatment response in terms of adherence, physical
activity, mental attitude, social support, and self-awareness. Adherence was
described as the foundation for the patients' own influence on good treatment
response. Physical activity, mental attitude, and social support reflected three
essential ways of understanding patients' influence on good treatment response
where the patients spoke about physical strength, mental strength, and social
strength. Self-awareness reflected a comprehensive way of influencing good
treatment response in which patients balanced their physical, mental, and social
resources in partnership with health care professionals. CONCLUSION: Patients
conceived that they had a responsibility for adhering to the treatment as well as
achieving balance in life in order to ensure good treatment response. Self
awareness was essential for maintaining a good treatment response, and this
reflected the patients' awareness of the complexity of living their lives with a
chronic illness.
PMID- 28706445
TI - Histone demethylase KDM2B upregulates histone methyltransferase EZH2 expression
and contributes to the progression of ovarian cancer in vitro and in vivo.
AB - Aberrant histone methylation contributes to the progression and development of
many tumors. Histone methylation is a dynamic process regulated by both histone
demethylase and histone methyltransferase, which ultimately alters the levels of
gene transcription. However, the relationship between histone demethylase and
histone methyltransferase, as well as their regulatory mechanisms in ovarian
cancer development, is still unclear. Lysine-specific demethylase 2B (KDM2B) is a
key demethylase of H3K36me3 and H3K4me3 that regulates gene expression and plays
a role in tumorigenesis via epigenetic mechanisms. To determine the expression
pattern of KDM2B in ovarian neoplasms, we analyzed the mRNA and protein levels of
KDM2B and the histone methyltransferase enhancer of zester homolog 2 (EZH2) in
normal, benign, borderline, and malignant ovarian tissue samples. We found that
KDM2B expression was gradually increased in ovarian tumors, with the highest
expression found in the malignant ovarian tissues, and the differences in KDM2B
expression among the different International Federation of Gynecology and
Obstetrics stages and pathological grades/types were statistically significant.
Moreover, KDM2B expression was positively correlated with EZH2 expression in
ovarian tissues. To determine the role of KDM2B in tumorigenesis in vitro and in
vivo, we silenced KDM2B expression in ovarian cancer cells using the KDM2B short
hairpin RNA expression lentivirus and established a nude mouse xenograft model.
Downregulation of endogenous KDM2B decreased the expression of EZH2 and reduced
the proliferation and migration of ovarian cancer cells. Loss of KDM2B suppressed
ovarian tumor formation in vivo. Our results suggest that KDM2B plays an
important role in the tumorigenesis of ovarian cancer, with a possible mechanism
of increasing the expression of the oncogene EZH2; this indicates that certain
histone methyltransferase may be positively regulated by certain histone
demethylase in the epigenetic regulation of ovarian tumors. KDM2B may be a novel
therapeutic target for the clinical treatment of ovarian cancer.
PMID- 28706446
TI - Derived neutrophil to lymphocyte ratio and monocyte to lymphocyte ratio may be
better biomarkers for predicting overall survival of patients with advanced
gastric cancer.
AB - BACKGROUND AND OBJECTIVES: Preoperative systemic inflammatory response and
nutritional status play important roles in the tumorigenesis, progression, and
prognosis of gastric cancer (GC). This research is designed to investigate the
prognostic value of the biomarkers including the neutrophil to lymphocyte ratio
(NLR), derived neutrophil to lymphocyte ratio (dNLR), monocyte to lymphocyte
ratio (MLR), platelet to lymphocyte ratio (PLR), and prognostic nutritional index
(PNI) in predicting overall survival in patients with GC. METHODS: A total of
1,990 consecutive GC patients who underwent gastrectomy from 2007 to 2011 were
enrolled and divided into high level and low level based on the optimal cut-off
points for NLR, dNLR, MLR, PLR, and PNI, respectively. The clinicopathological
characteristics of the two levels were comparatively analyzed. Overall survival
analysis was executed using these biomarkers and clinicopathological
characteristics. RESULTS: The number of metastatic lymph nodes, distant
metastasis, American Joint Committee on Cancer TNM stage, radicality, tumor size,
metastatic lymph nodes ratio, ascites, and Hb were all significantly associated
with NLR, dNLR, MLR, PLR, and PNI. All of these five biomarkers were closely
associated with overall survival in univariate analyses, but only dNLR and MLR
were significant in multivariate model. dNLR and MLR can be bonded to predict
survival, but whether separate or together, dNLR and MLR were mainly significant
in advanced stages. CONCLUSION: Although preoperative NLR, dNLR, MLR, PLR, and
PNI in peripheral blood proved significant prediction of prognoses of
postoperative GC patients, dNLR and MLR may be better biomarkers for predicting
overall survival, especially in advanced GC patients.
PMID- 28706447
TI - Treatment patterns, resource utilization, and outcomes among hospitalized
patients with methicillin-resistant Staphylococcus aureus complicated skin and
soft tissue infections in Lebanon and Saudi Arabia.
AB - OBJECTIVES: To describe treatment patterns and medical resource use for
methicillin-resistant Staphylococcus aureus (MRSA) complicated skin and soft
tissue infections (cSSTI) in Saudi Arabia and Lebanon in terms of drug selection
against the infecting pathogen as well as hospital resource utilization and
clinical outcomes among patients with these infections. METHODS: This
retrospective chart review study evaluated 2011-2012 data from five hospitals in
Saudi Arabia and Lebanon. Patients were included if they had been discharged with
a diagnosis of MRSA cSSTI, which was culture-proven or suspected based on
clinical criteria. Hospital data were abstracted for a random sample of patients
with each infection type to capture demographics, treatment patterns, hospital
resource utilization, and clinical outcomes. Statistical analysis was
descriptive. RESULTS: Data were abstracted from medical records of 87 patients
with MRSA cSSTI; mean age 52.4+/-25.9 years and 61% male. Only 64% of patients
received an MRSA active initial therapy, with 56% of first-line regimens
containing older beta-lactams. The mean total length of stay was 26.3 days, with
the majority (19.1 days) spent in general wards. Surgical procedures included
incision and drainage (22% of patients), debridement (14%), and amputation (5%).
Mechanical ventilation was required by 9% of patients, with a mean duration of 18
days per patient. Hemodialysis was required by four patients (5%), two of whom
were reported to have moderate to severe renal disease on admission, for a mean
of 5.5 days. Inpatient mortality was 8%. Thirty-nine percent were prescribed at
least one antibiotic at discharge, with the most commonly prescribed discharge
antibiotics being clindamycin (44%), ciprofloxacin (18%),
trimethoprim/sulfamethoxazole (12%), and linezolid (9%). CONCLUSION: This Middle
Eastern real-world study of resource use and treatment patterns in MRSA cSSTI
indicates that management of this condition could be further optimized in terms
of drug selection and resource utilization.
PMID- 28706448
TI - Genotypic distribution of multidrug-resistant and extensively drug-resistant
tuberculosis in northern Thailand.
AB - BACKGROUND: Multidrug/extensively drug-resistant tuberculosis (M/XDR-TB) is a
major public health problem, and early detection is important for preventing its
spread. This study aimed to demonstrate the distribution of genetic site mutation
associated with drug resistance in M/XDR-TB in the northern Thai population.
METHODS: Thirty-four clinical MTB isolates from M/XDR-TB patients in the upper
northern region of Thailand, who had been identified for drug susceptibility
using the indirect agar proportion method from 2005 to 2012, were examined for
genetic site mutations of katG, inhA, and ahpC for isoniazid (INH) drug
resistance and rpoB for rifampicin (RIF) drug resistance. The variables included
the baseline characteristics of the resistant gene, genetic site mutations, and
drug susceptibility test results. RESULTS: All 34 isolates resisted both INH and
RIF. Thirty-two isolates (94.1%) showed a mutation of at least 1 codon for katG,
inhA, and ahpC genes. Twenty-eight isolates (82.4%) had a mutation of at least 1
codon of rpoB gene. The katG, inhA, ahpC, and rpoB mutations were detected in 20
(58.7%), 27 (79.4%), 13 (38.2%), and 28 (82.3%) of 34 isolates. The 3 most common
mutation codons were katG 315 (11/34, 35.3%), inhA 14 (11/34, 32.4%), and inhA
114 (11/34, 32.4%). For this population, the best genetic mutation test panels
for INH resistance included 8 codons (katG 310, katG 340, katG 343, inhA 14, inhA
84, inhA 86, inhA 114, and ahpC 75), and for RIF resistance included 6 codons
(rpoB 445, rpoB 450, rpoB 464, rpoB 490, rpoB 507, and rpoB 508) with a
sensitivity of 94.1% and 82.4%, respectively. CONCLUSION: The genetic mutation
sites for drug resistance in M/XDR-TB are quite variable. The distribution of
these mutations in a certain population must be studied before developing the
specific mutation test panels for each area. The results of this study can be
applied for further molecular M/XDR-TB diagnosis in the upper northern region of
Thailand.
PMID- 28706449
TI - Effects of tianeptine on symptoms of fibromyalgia via BDNF signaling in a
fibromyalgia animal model.
AB - Previous reports have suggested that physical and psychological stresses may
trigger fibromyalgia (FM). Stress is an important risk factor in the development
of depression and memory impairments. Antidepressants have been used to prevent
stress-induced abnormal pain sensation. Among various antidepressants, tianeptine
has been reported to be able to prevent neurodegeneration due to chronic stress
and reverse decreases in hippocampal volume. To assess the possible effect of
tianeptine on FM symptoms, we constructed a FM animal model induced by restraint
stress with intermittent cold stress. All mice underwent nociceptive assays using
electronic von Frey anesthesiometer and Hargreaves equipment. To assess the
relationship between tianeptine and expression levels of brain-derived
neurotrophic factor (BDNF), cAMP response element-binding protein (CREB), and
phosphorylated cAMP response element-binding protein (p-CREB), western blotting
and immunohistochemistry analyses were performed. In behavioral analysis,
nociception tests showed that pain threshold was significantly decreased in the
FM group compared to that in the control group. Western blot and
immunohistochemical analyses of medial prefrontal cortex (mPFC) and hippocampus
showed downregulation of BDNF and p-CREB proteins in the FM group compared to the
control group. However, tianeptine recovered these changes in behavioral tests
and protein level. Therefore, this FM animal model might be useful for
investigating mechanisms linking BDNF-CREB pathway and pain. Our results suggest
that tianeptine might potentially have therapeutic efficacy for FM.
PMID- 28706450
TI - Reactive oxygen species increase neuronal excitability via activation of
nonspecific cation channel in rat medullary dorsal horn neurons.
AB - The caudal subnucleus of the spinal trigeminal nucleus (medullary dorsal horn;
MDH) receives direct inputs from small diameter primary afferent fibers that
predominantly transmit nociceptive information in the orofacial region. Recent
studies indicate that reactive oxygen species (ROS) is involved in persistent
pain, primarily through spinal mechanisms. In this study, we aimed to investigate
the role of xanthine/xanthine oxidase (X/XO) system, a known generator of
superoxide anion (O2.-), on membrane excitability in the rat MDH neurons. For
this, we used patch clamp recording and confocal imaging. An application of X/XO
(300 uM/30 mU) induced membrane depolarization and inward currents. When slices
were pretreated with ROS scavengers, such as phenyl N-tert-butylnitrone (PBN),
superoxide dismutase (SOD), and catalase, X/XO-induced responses decreased.
Fluorescence intensity in the DCF-DA and DHE-loaded MDH cells increased on the
application of X/XO. An anion channel blocker, 4,4-diisothiocyanatostilbene-2,2
disulfonic acid (DIDS), significantly decreased X/XO-induced depolarization. X/XO
elicited an inward current associated with a linear current-voltage relationship
that reversed near -40 mV. X/XO-induced depolarization reduced in the presence of
La3+, a nonselective cation channel (NSCC) blocker, and by lowering the external
sodium concentration, indicating that membrane depolarization and inward current
are induced by influx of Na+ ions. In conclusion, X/XO-induced ROS modulate the
membrane excitability of MDH neurons, which was related to the activation of
NSCC.
PMID- 28706451
TI - Protein kinase C beta II upregulates intercellular adhesion molecule-1 via
mitochondrial activation in cultured endothelial cells.
AB - Activation of protein kinase C (PKC) is closely linked with endothelial
dysfunction. However, the effect of PKCbetaII on endothelial dysfunction has not
been characterized in cultured endothelial cells. Here, using adenoviral
PKCbetaII gene transfer and pharmacological inhibitors, the role of PKCbetaII on
endothelial dysfucntion was investigated in cultured endothelial cells. Phorbol
12-myristate 13-acetate (PMA) increased reactive oxygen species (ROS), p66shc
phosphorylation, intracellular adhesion molecule-1, and monocyte adhesion, which
were inhibited by PKCbetai (10 nM), a selective inhibitor of PKCbetaII. PMA
increased the phosphorylation of CREB and manganese superoxide dismutase (MnSOD),
which were also inhibited by PKCbetai. Gene silencing of CREB inhibited PMA
induced MnSOD expression, suggesting that CREB plays a key role in MnSOD
expression. Gene silencing of PKCbetaII inhibited PMA-induced mitochondrial ROS,
MnSOD, and ICAM-1 expression. In contrast, overexpression of PKCbetaII using
adenoviral PKCbetaII increased mitochondrial ROS, MnSOD, ICAM-1, and p66shc
phosphorylation in cultured endothelial cells. Finally, PKCbetaII-induced ICAM-1
expression was inhibited by Mito-TEMPO, a mitochondrial ROS scavenger, suggesting
the involvement of mitochondrial ROS in PKC-induced vascular inflammation. Taken
together, the results suggest that PKCbetaII plays an important role in PMA
induced endothelial dysfunction, and that the inhibition of PKCbetaII-dependent
p66shc signaling acts as a therapeutic target for vascular inflammatory diseases.
PMID- 28706452
TI - Elucidation of the profound antagonism of contractile action of phenylephrine in
rat aorta effected by an atypical sympathomimetic decongestant.
AB - Vasoconstrictive properties of sympathomimetic drugs are the basis of their
widespread use as decongestants and possible source of adverse responses.
Insufficiently substantiated practice of combining decongestants in some marketed
preparations, such are those containing phenylephrine and lerimazoline, may
affect the overall contractile activity, and thus their therapeutic utility. This
study aimed to examine the interaction between lerimazoline and phenylephrine in
isolated rat aortic rings, and also to assess the substrate of the obtained
lerimazoline-induced attenuation of phenylephrine contraction. Namely, while
lower concentrations of lerimazoline (10-6 M and especially 10-7 M) expectedly
tended to potentiate the phenylephrine-induced contractions, lerimazoline in
higher concentrations (10-4 M and above) unexpectedly and profoundly depleted the
phenylephrine concentration-response curve. Suppression of NO with NO synthase
(NOS) inhibitor Nw-nitro-L-arginine methyl ester (L-NAME; 10-4 M) or NO scavanger
OHB12 (10-3 M), as well as non-specific inhibition of K+-channels with
tetraethylammonium (TEA; 10-3 M), have reversed lerimazoline-induced relaxation
of phenylephrine contractions, while cyclooxygenase inhibitor indomethacin (10-5
M) did not affect the interaction between two vasoconstrictors. At the receptor
level, non-selective 5-HT receptor antagonist methiothepin reversed the
attenuating effect of lerimazoline on phenylephrine contraction when applied at
3*10-7 and 10-6 M, but not at the highest concentration (10-4 M). Neither the 5
HT1D-receptor selective antagonist BRL 15572 (10-6 M) nor 5-HT7 receptor
selective antagonist SB 269970 (10-6 M) affected the lerimazoline-induced
attenuation of phenylephrine activity. The mechanism of lerimazoline-induced
suppression of phenylephrine contractions may involve potentiation of activity of
NO and K+-channels and activation of some methiothepin-sensitive receptors,
possibly of the 5-HT2B subtype.
PMID- 28706453
TI - MDL-12330A potentiates TRAIL-induced apoptosis in gastric cancer cells through
CHOP-mediated DR5 upregulation.
AB - MDL-12330A is a widely used adenylyl cyclase (AC) inhibitor that blocks AC/cAMP
signaling. In this study, we demonstrated a novel antitumor activity of this drug
in gastric carcinoma (GC) cell lines. In these GC cells, MDL-12330A reduced cell
viability and induced cell death in a concentration-dependent manner. At a
moderate concentration (~20 uM), MDL-12330A mainly induced apoptotic death
whereas at concentrations greater than 20 uM, it increased non-apoptotic cell
death. The induction of apoptosis was at least partially regulated by CHOP
mediated DR5 upregulation, as detected by immunoblotting and gene interference
assays. More importantly, low concentrations of MDL-12330A effectively enhanced
recombinant human tumor necrosis factor (TNF)-related apoptosis-inducing ligand
(rhTRAIL)-induced apoptosis and clonogenicity in these gastric cancer cells. This
study demonstrates a possible role of MDL-12330A as a potential sensitizer to
TRAIL, and suggests a novel therapeutic strategy targeting gastric cancer cells.
PMID- 28706454
TI - Participation of COX-1 and COX-2 in the contractile effect of phenylephrine in
prepubescent and old rats.
AB - Vascular reactivity can be influenced by the vascular region, animal age, and
pathologies present. Prostaglandins (produced by COX-1 and COX-2) play an
important role in the contractile response to phenylephrine in the abdominal
aorta of young rats. Although these COXs are found in many tissues, their
distribution and role in vascular reactivity are not clear. At a vascular level,
they take part in the homeostasis functions involved in many physiological and
pathologic processes (e.g., arterial pressure and inflammatory processes). The
aim of this study was to analyze changes in the contractile response to
phenylephrine of thoracic/abdominal aorta and the coronary artery during aging in
rats. Three groups of rats were formed and sacrificed at three distinct ages:
prepubescent, young and old adult. The results suggest that there is a higher
participation of prostanoids in the contractile effect of phenylephrine in pre
pubescent rats, and a lower participation of the same in old rats. Contrarily,
there seems to be a higher participation of prostanoids in the contractile
response of the coronary artery of older than pre-pubescent rats. Considering
that the changes in the expression of COX-2 were similar for the three age groups
and the two tissues tested, and that expression of COX-1 is apparently greater in
older rats, COX-1 and COX-2 may lose functionality in relation to their
corresponding receptors during aging in rats.
PMID- 28706455
TI - Escitalopram, a selective serotonin reuptake inhibitor, inhibits voltage
dependent K+ channels in coronary arterial smooth muscle cells.
AB - We investigated the inhibitory effect of escitalopram, a selective serotonin
reuptake inhibitor (SSRI), on voltage-dependent K+ (Kv) channels in freshly
separated from rabbit coronary arterial smooth muscle cells. The application of
escitalopram rapidly inhibited vascular Kv channels. Kv currents were
progressively inhibited by an increase in the concentrations of escitalopram,
suggesting that escitalopram inhibited vascular Kv currents in a concentration
dependent manner. The IC50 value and Hill coefficient for escitalopram-induced
inhibition of Kv channels were 9.54+/-1.33 uM and 0.75+/-0.10, respectively.
Addition of escitalopram did not alter the steady-state activation and
inactivation curves, suggesting that the voltage sensors of the channels were not
affected. Pretreatment with inhibitors of Kv1.5 and/or Kv2.1 did not affect the
inhibitory action of escitalopram on vascular Kv channels. From these results, we
concluded that escitalopram decreased the vascular Kv current in a concentration
dependent manner, independent of serotonin reuptake inhibition.
PMID- 28706456
TI - Reduction of long-term potentiation at Schaffer collateral-CA1 synapses in the
rat hippocampus at the acute stage of vestibular compensation.
AB - Vestibular compensation is a recovery process from vestibular symptoms over time
after unilateral loss of peripheral vestibular end organs. The aim of the present
study was to observe time-dependent changes in long-term potentiation (LTP) at
Schaffer collateral-CA1 synapses in the CA1 area of the hippocampus during
vestibular compensation. The input-output (I/O) relationships of fEPSP amplitudes
and LTP induced by theta burst stimulation to Schaffer's collateral commissural
fibers were evaluated from the CA1 area of hippocampal slices at 1 day, 1 week,
and 1 month after unilateral labyrinthectomy (UL). The I/O relationships of
fEPSPs in the CA1 area was significantly reduced within 1 week post-op and then
showed a non-significant reduction at 1 month after UL. Compared with sham
operated animals, there was a significant reduction of LTP induction in the
hippocampus at 1 day and 1 week after UL. However, LTP induction levels in the
CA1 area of the hippocampus also returned to those of sham-operated animals 1
month following UL. These data suggest that unilateral injury of the peripheral
vestibular end organs results in a transient deficit in synaptic plasticity in
the CA1 hippocampal area at acute stages of vestibular compensation.
PMID- 28706457
TI - Relaxant and anti-inflammatory effect of two thalidomide analogs as PDE-4
inhibitors in pregnant rat uterus.
AB - The aim of this study was to evaluate the relaxant and anti-inflammatory effects
of two thalidomide analogs as phosphodiesterase-4 (PDE-4) inhibitors in pregnant
rat uterus. Uteri from Wistar female rats were isolated at 19 day of pregnancy.
Uterine samples were used in functional studies to evaluate the inhibitory
effects of the thalidomide analogs, methyl 3-(4-nitrophthalimido)-3-(3,4
dimethoxyphenyl)-propanoate (4NO2PDPMe) and methyl 3-(4-aminophthalimido)-3-(3,4
dimethoxyphenyl)-propanoate (4APDPMe), on prostaglandin-F2alpha (PGF2alpha)
induced phasic, K+-induced tonic, and Ca2+-induced contractions. Accumulation of
cAMP was quantified in uterine homogenates by ELISA. Anti-inflammatory effect was
assessed by using ELISA for determination of the pro-inflammatory cytokines tumor
necrosis factor-alpha (TNFalpha) and interleukin (IL)-1beta, and anti
inflammatory IL-10, from uterine explants stimulated with lipopolysaccharide
(LPS). Nifedipine, forskolin and rolipram were used as positive controls where
required. Both thalidomide analogs induced a significant inhibition of the
uterine contractions induced by the pharmaco- and electro-mechanic stimuli.
Nifedipine and forskolin were more potent than the analogs to inhibit the uterine
contractility, but these were more potent than rolipram, and 4APDPMe was
equieffective to nifedipine. Thalidomide analogs increased uterine cAMP-levels in
a concentration-dependent manner. The LPS-induced TNFalpha and IL-1beta uterine
secretion was diminished in a concentration-dependent fashion by both analogs,
whereas IL-10 secretion was increased significantly. The thalidomide analogs
induced utero-relaxant and anti-inflammatory effects, which were associated with
the increased cAMP levels as PDE-4 inhibitors in the pregnant rat uterus. Such
properties place these thalidomide analogs as potentially safe and effective
tocolytic agents in a field that urgently needs improved pharmacological
treatments, as in cases of preterm labor.
PMID- 28706458
TI - Electrophysiological characteristics of R47W and A298T mutations in CLC-1 of
myotonia congenita patients and evaluation of clinical features.
AB - Myotonia congenita (MC) is a genetic disease that displays impaired relaxation of
skeletal muscle and muscle hypertrophy. This disease is mainly caused by
mutations of CLCN1 that encodes human skeletal muscle chloride channel (CLC-1).
CLC-1 is a voltage gated chloride channel that activates upon depolarizing
potentials and play a major role in stabilization of resting membrane potentials
in skeletal muscle. In this study, we report 4 unrelated Korean patients
diagnosed with myotonia congenita and their clinical features. Sequence analysis
of all coding regions of the patients was performed and mutation, R47W and A298T,
was commonly identified. The patients commonly displayed transient muscle
weakness and only one patient was diagnosed with autosomal dominant type of
myotonia congenita. To investigate the pathological role of the mutation,
electrophysiological analysis was also performed in HEK 293 cells transiently
expressing homo- or heterodimeric mutant channels. The mutant channels displayed
reduced chloride current density and altered channel gating. However, the effect
of A298T on channel gating was reduced with the presence of R47W in the same
allele. This analysis suggests that impaired CLC-1 channel function can cause
myotonia congenita and that R47W has a protective effect on A298T in relation to
channel gating. Our results provide clinical features of Korean myotonia
congenita patients who have the heterozygous mutation and reveal underlying
pathophyological consequences of the mutants by taking electrophysiological
approach.
PMID- 28706459
TI - Beauvericin, a cyclic peptide, inhibits inflammatory responses in macrophages by
inhibiting the NF-kappaB pathway.
AB - Beauvericin (BEA), a cyclic hexadepsipeptide produced by the fungus Beauveria
bassiana, is known to have anti-cancer, anti-inflammatory, and anti-microbial
actions. However, how BEA suppresses macrophage-induced inflammatory responses
has not been fully elucidated. In this study, we explored the anti-inflammatory
properties of BEA and the underlying molecular mechanisms using
lipopolysaccharide (LPS)-treated macrophage-like RAW264.7 cells. Levels of nitric
oxide (NO), mRNA levels of transcription factors and the inflammatory genes
inducible NO synthase (iNOS) and interleukin (IL)-1, and protein levels of
activated intracellular signaling molecules were determined by Griess assay, semi
quantitative reverse transcriptase-polymerase chain reaction (RT-PCR), luciferase
reporter gene assay, and immunoblotting analysis. BEA dose-dependently blocked
the production of NO in LPS-treated RAW264.7 cells without inducing cell
cytotoxicity. BEA also prevented LPS-triggered morphological changes. This
compound significantly inhibited nuclear translocation of the NF-kappaB subunits
p65 and p50. Luciferase reporter gene assays demonstrated that BEA suppresses
MyD88-dependent NF-kappaB activation. By analyzing upstream signaling events for
NF-kappaB activation and overexpressing Src and Syk, these two enzymes were
revealed to be targets of BEA. Together, these results suggest that BEA
suppresses NF-kappaB-dependent inflammatory responses by suppressing both Src and
Syk.
PMID- 28706460
TI - Pricing timer options and variance derivatives with closed-form partial transform
under the 3/2 model.
AB - Most of the empirical studies on stochastic volatility dynamics favour the 3/2
specification over the square-root (CIR) process in the Heston model. In the
context of option pricing, the 3/2 stochastic volatility model (SVM) is reported
to be able to capture the volatility skew evolution better than the Heston model.
In this article, we make a thorough investigation on the analytic tractability of
the 3/2 SVM by proposing a closed-form formula for the partial transform of the
triple joint transition density [Formula: see text] which stand for the log asset
price, the quadratic variation (continuous realized variance) and the
instantaneous variance, respectively. Two distinct formulations are provided for
deriving the main result. The closed-form partial transform enables us to deduce
a variety of marginal partial transforms and characteristic functions and plays a
crucial role in pricing discretely sampled variance derivatives and exotic
options that depend on both the asset price and quadratic variation. Various
applications and numerical examples on pricing moment swaps and timer options
with discrete monitoring feature are given to demonstrate the versatility of the
partial transform under the 3/2 model.
PMID- 28706461
TI - Caregiver involvement in behavioural health services in the context of child
welfare service referrals: a qualitative study.
AB - Human service agencies serve a growing number of adults with behavioral health
needs. Despite these agencies' key role in identifying need and facilitating
services, many individuals do not receive care or end services prematurely. Few
studies have explored the experiences of families referred to behavioral health
services by such agencies or the extent to which families' perceptions of service
need align with those of treatment providers and frontline workers. This study
presents findings from a qualitative study of caregivers involved with child
welfare agencies who were referred to behavioral health services. Researchers
reviewed agencies' case records and conducted in-depth interviews with 16
caregivers, 9 child welfare caseworkers, and 12 behavioral health treatment
counselors. Findings suggest that when deciding to engage in services, caregivers
weigh not only their individual and family behavioral health needs but also
potential agency intervention, including loss of child custody. Many
professionals reported that involvement with a child welfare agency hindered the
caregiver's disclosure of behavioral health care needs. Implications for managers
and practitioners are discussed.
PMID- 28706462
TI - Predictors of Wound Complications following Radiation and Surgical Resection of
Soft Tissue Sarcomas.
AB - Wound complications represent a major source of morbidity in patients undergoing
radiation therapy (RT) and surgical resection of soft tissue sarcomas (STS). We
investigated whether factors related to RT, surgery, patient comorbidities, and
tumor histopathology predict the development of wound complications. An
observational study of patients who underwent STS resection and RT was performed.
The primary outcome was the occurrence of any wound complication up to four
months postoperatively. Significant predictors of wound complications were
identified using multivariable logistic regression. Sixty-five patients
representing 67 cases of STS were identified. Median age was 59 years (range 22
90) and 34 (52%) patients were female. The rates of major wound complications and
any wound complications were 21% and 33%, respectively. After adjusting for
radiation timing, diabetes (OR 9.6; 95% CI 1.4-64.8; P = 0.02), grade >=2
radiation dermatitis (OR 4.8; 95% CI 1.2-19.2; P = 0.03), and the use of 3D
conformal RT (OR 4.6; 95% CI 1.1-20.0; P = 0.04) were associated with an
increased risk of any wound complication on multivariable analysis. These data
suggest that radiation dermatitis and radiation modality are predictors of wound
complications in patients with STS.
PMID- 28706463
TI - Estimates and Standard Errors for Ratios of Normalizing Constants from Multiple
Markov Chains via Regeneration.
AB - In the classical biased sampling problem, we have k densities pi1(.), ..., pik
(.), each known up to a normalizing constant, i.e. for l = 1, ..., k, pil (.) =
nul (.)/ml , where nul (.) is a known function and ml is an unknown constant. For
each l, we have an iid sample from pil ,.and the problem is to estimate the
ratios ml/ms for all l and all s. This problem arises frequently in several
situations in both frequentist and Bayesian inference. An estimate of the ratios
was developed and studied by Vardi and his co-workers over two decades ago, and
there has been much subsequent work on this problem from many different
perspectives. In spite of this, there are no rigorous results in the literature
on how to estimate the standard error of the estimate. We present a class of
estimates of the ratios of normalizing constants that are appropriate for the
case where the samples from the pil 's are not necessarily iid sequences, but are
Markov chains. We also develop an approach based on regenerative simulation for
obtaining standard errors for the estimates of ratios of normalizing constants.
These standard error estimates are valid for both the iid case and the Markov
chain case.
PMID- 28706464
TI - Telemedicine-based proactive patient management during positive airway pressure
therapy: Impact on therapy termination rate.
AB - BACKGROUND: Adherence to positive airway pressure (PAP) therapy is essential for
the benefits of therapy to be realised. Telemedicine-based strategies provide a
new option for enhanced monitoring and intervention to promote adherence during
PAP. This study investigated the impact of telemedicine-based proactive patient
management on PAP therapy termination rates versus standard care. METHODS:
Observational data were obtained from ResMed Germany Healthcare, a German
homecare provider. Patients were undergoing routine homecare using either a
standard or proactive management strategy. The proactive strategy used data from
AirViewTM, a cloud-based remote monitoring system, to prompt patient contact and
information sharing/education. Patients receiving their first PAP therapy were
included and analysed in matched pairs. RESULTS: In all, 3401 patients were
included in each group. In the first year of PAP therapy, overall therapy
termination rate was significantly lower (5.4% vs 11.0%; p < 0.001) and time to
therapy termination was significantly longer (348 +/- 58 vs 337 +/- 76 days; p <
0.05) in the proactive versus standard care group. Cox proportional hazard
analysis revealed a significantly reduced risk of PAP termination in the
proactive versus the standard care group (hazard ratio 0.48, 95% confidence
interval 0.4-0.57). Findings were consistent in subanalyses according to gender,
type of device and insurance status, and in patients aged >=40 years. However, in
the subgroup of patients aged younger than 40 years, the risk of PAP termination
was similar in the proactive and standard groups. CONCLUSION: A telemedicine
based proactive management strategy compared with standard care of PAP patients
was associated with a lower long-term therapy termination rate.
PMID- 28706465
TI - Disability and the Family in South Wales Coalfield Society, c.1920-1939.
AB - This article utilises the south Wales coalfield in the interwar period as a case
study to illustrate the applicability of two sociological theories - family
systems theory and the social ecology of the family - to impairment in the past.
It demonstrates that a theoretically-informed approach can help to situate
impairment in its particular contexts, most especially the family and the
community, and give a better sense of the lived experience of disability. It also
demonstrates the complexity of the experience of disability as the family and
economic circumstances of each impaired individual varied and led to different
forms of care-giving or the utilisation of different sources of support. The
article also sheds further light on the ubiquity of disability as many families
included a number of individuals with different impairments and this too had
consequences for experiences and coping strategies.
PMID- 28706466
TI - Modeling the potential impact of emerging innovations on achievement of
Sustainable Development Goals related to maternal, newborn, and child health.
AB - BACKGROUND: Innovations that improve the affordability, accessibility, or
effectiveness of health care played a major role in the Millennium Development
Goal achievements and will be critical for reaching the ambitious new Sustainable
Development Goal (SDG) health targets. Mechanisms to identify and prioritize
innovations are essential to inform future investment decisions. METHODS:
Innovation Countdown 2030 crowdsourced health innovations from around the world
and engaged recognized experts to systematically assess their lifesaving
potential by 2030. A health impact modeling approach was developed and used to
quantify the costs and lives saved for select innovations identified as having
great promise for improving maternal, newborn, and child health. RESULTS:
Preventive innovations targeting health conditions with a high mortality burden
had the greatest impact in regard to the absolute number of estimated lives
saved. The largest projected health impact was for a new tool for small-scale
water treatment that automatically chlorinates water to a safe concentration
without using electricity or moving parts. An estimated 1.5 million deaths from
diarrheal disease among children under five could be prevented by 2030 by scaling
up use of this technology. Use of chlorhexidine for umbilical cord care was
associated with the second highest number of lives saved. CONCLUSIONS: The
results show why a systematic modeling approach that can compare and contrast
investment opportunities is important for prioritizing global health innovations.
Rigorous impact estimates are needed to allocate limited resources toward the
innovations with great potential to advance the SDGs.
PMID- 28706467
TI - Ketogenic diet benefits body composition and well-being but not performance in a
pilot case study of New Zealand endurance athletes.
AB - BACKGROUND: Low-carbohydrate, high-fat and ketogenic diets are increasingly
adopted by athletes for body composition and sports performance enhancements.
However, as yet, there is no consensus on their efficacy in improving
performance. There is also no comprehensive literature on athletes' experiences
while undertaking this diet. The purpose of this pilot work was two-fold: i. to
examine the effects of a non-calorie controlled ketogenic diet on body
composition and performance outcomes of endurance athletes, and ii. to evaluate
the athletes' experiences of the ketogenic diet during the 10-week intervention.
METHODS: Using a case study design, five New Zealand endurance athletes (4
females, 1 male) underwent a 10-week ketogenic dietary intervention. Body
composition (sum of 8 skinfolds), performance indicators (time to exhaustion, VO2
max, peak power and ventilatory threshold), and gas exchange thresholds were
measured at baseline and at 10 weeks. Mean change scores were calculated, and
analysed using t-tests; Cohen's effect sizes and 90% confidence limits were
applied to quantify change. Individual interviews conducted at 5 weeks and a
focus group at 10 weeks assessed athletes' ketogenic diet experiences. Data was
transcribed and analysed using thematic analysis. RESULTS: All athletes increased
their ability to utilise fat as a fuel source, including at higher exercise
intensities. Mean body weight was reduced by 4 kg +/- SD 3.1 (p = 0.046; effect
size (ES):0.62), and sum of 8 skinfolds by 25.9 mm +/- SD 6.9; ES: 1.27; p =
0.001). Mean time to exhaustion dropped by ~2 min (+/-SD 0.7; p = 0.004; ES:
0.53). Other performance outcomes showed mean reductions, with some increases or
unchanged results in two individuals (VO2 Max: -1.69 ml.kg.min +/- SD 3.4 (p =
0.63); peak power: -18 W +/- SD 16.4 (p = 0.07), and VT2: -6 W +/- SD 44.5 (p =
0.77). Athletes reported experiencing reduced energy levels initially, followed
by a return of high levels thereafter, especially during exercise, but an
inability to easily undertake high intense bouts. Each athlete reported
experiencing enhanced well-being, included improved recovery, improvements in
skin conditions and reduced inflammation. CONCLUSIONS: Despite performance
decrements and some negative experiences, athletes were keen to pursue a modified
low-carbohydrate, high-fat eating style moving forward due to the unexpected
health benefits they experienced. TRIAL REGISTRATION: ACTRN: ACTRN12617000613303.
Registered 28 April 2017, retrospectively registered.
PMID- 28706468
TI - Retinal metabolic events in preconditioning light stress as revealed by wide
spectrum targeted metabolomics.
AB - INTRODUCTION: Light is the primary stimulus for vision, but may also cause damage
to the retina. Pre-exposing the retina to sub-lethal amount of light (or
preconditioning) improves chances for retinal cells to survive acute damaging
light stress. OBJECTIVES: This study aims at exploring the changes in retinal
metabolome after mild light stress and identifying mechanisms that may be
involved in preconditioning. METHODS: Retinas from 12 rats exposed to mild light
stress (1000 lux * for 12 h) and 12 controls were collected one and seven days
after light stress (LS). One retina was used for targeted metabolomics analysis
using the Biocrates p180 kit while the fellow retina was used for histological
and immunohistochemistry analysis. RESULTS: Immunohistochemistry confirmed that
in this experiment, a mild LS with retinal immune response and minimal
photoreceptor loss occurred. Compared to controls, LS induced an increased
concentration in phosphatidylcholines. The concentration in some amino acids and
biogenic amines, particularly those related to the nitric oxide pathway (like
asymmetric dimethylarginine (ADMA), arginine and citrulline) also increased 1 day
after LS. 7 days after LS, the concentration in two sphingomyelins and
phenylethylamine was found to be higher. We further found that in controls,
retina metabolome was different between males and females: male retinas had an
increased concentration in tyrosine, acetyl-ornithine, phosphatidylcholines and
(acyl)-carnitines. CONCLUSIONS: Besides retinal sexual metabolic dimorphism, this
study shows that preconditioning is mostly associated with re-organisation of
lipid metabolism and changes in amino acid composition, likely reflecting the
involvement of arginine-dependent NO signalling.
PMID- 28706469
TI - Metabolic response of porcine colon explants to in vitro infection by Brachyspira
hyodysenteriae: a leap into disease pathophysiology.
AB - INTRODUCTION: Swine dysentery caused by Brachyspira hyodysenteriae is a
production limiting disease in pig farming. Currently antimicrobial therapy is
the only treatment and control method available. OBJECTIVE: The aim of this study
was to characterize the metabolic response of porcine colon explants to infection
by B. hyodysenteriae. METHODS: Porcine colon explants exposed to B.
hyodysenteriae were analyzed for histopathological, metabolic and pro
inflammatory gene expression changes. RESULTS: Significant epithelial necrosis,
increased levels of l-citrulline and IL-1alpha were observed on explants infected
with B. hyodysenteriae. CONCLUSIONS: The spirochete induces necrosis in vitro
likely through an inflammatory process mediated by IL-1alpha and NO.
PMID- 28706470
TI - Structure elucidation of metabolite x17299 by interpretation of mass
spectrometric data.
AB - INTRODUCTION: A major bottleneck in metabolomic studies is metabolite
identification from accurate mass spectrometric data. Metabolite x17299 was
identified in plasma as an unknown in a metabolomic study using a compound
centric approach where the associated ion features of the compound were used to
determine the true molecular mass. OBJECTIVES: The aim of this work is to
elucidate the chemical structure of x17299, a new compound by de novo
interpretation of mass spectrometric data. METHODS: An Orbitrap Elite mass
spectrometer was used for acquisition of mass spectra up to MS4 at high
resolution. Synthetic standards of N,N,N-trimethyl-l-alanyl-l-proline betaine
(l,l-TMAP), a diastereomer, and an enantiomer were chemically prepared. RESULTS:
The planar structure of x17299 was successfully proposed by de novo mechanistic
interpretation of mass spectrometric data without any laborious purification and
nuclear magnetic resonance spectroscopic analysis. The proposed structure was
verified by deuterium exchanged mass spectrometric analysis and confirmed by
comparison to a synthetic standard. Relative configuration of x17299 was
determined by direct chromatographic comparison to a pair of synthetic
diastereomers. Absolute configuration was assigned after derivatization of x17299
with a chiral auxiliary group followed by its chromatographic comparison to a
pair of synthetic standards. CONCLUSION: The chemical structure of metabolite
x17299 was determined to be l,l-TMAP.
PMID- 28706471
TI - Scalable Text Mining Assisted Curation of Post-Translationally Modified
Proteoforms in the Protein Ontology.
AB - The Protein Ontology (PRO) defines protein classes and their interrelationships
from the family to the protein form (proteoform) level within and across species.
One of the unique contributions of PRO is its representation of post
translationally modified (PTM) proteoforms. However, progress in adding PTM
proteoform classes to PRO has been relatively slow due to the extensive manual
curation effort required. Here we report an automated pipeline for creation of
PTM proteoform classes that leverages two phosphorylation-focused text mining
tools (RLIMS-P, which detects mentions of kinases, substrates, and
phosphorylation sites, and eFIP, which detects phosphorylation-dependent protein
protein interactions (PPIs)) and our integrated PTM database, iPTMnet. By
applying this pipeline, we obtained a set of ~820 substrate-site pairs that are
suitable for automated PRO term generation with literature-based evidence
attribution. Inclusion of these terms in PRO will increase PRO coverage of
species-specific PTM proteoforms by 50%. Many of these new proteoforms also have
associated kinase and/or PPI information. Finally, we show a phosphorylation
network for the human and mouse peptidyl-prolyl cis-trans isomerase (PIN1/Pin1)
derived from our dataset that demonstrates the biological complexity of the
information we have extracted. Our approach addresses scalability in PRO curation
and will be further expanded to advance PRO representation of phosphorylated
proteoforms.
PMID- 28706472
TI - Relevant Feature Integration and Extraction for Single-Trial Motor Imagery
Classification.
AB - Brain computer interfaces provide a novel channel for the communication between
brain and output devices. The effectiveness of the brain computer interface is
based on the classification accuracy of single trial brain signals. The common
spatial pattern (CSP) algorithm is believed to be an effective algorithm for the
classification of single trial brain signals. As the amplitude feature for
spatial projection applied by this algorithm is based on a broad frequency
bandpass filter (mainly 5-30 Hz) in which the frequency band is often selected by
experience, the CSP is sensitive to noise and the influence of other irrelevant
information in the selected broad frequency band. In this paper, to improve the
CSP, a novel relevant feature integration and extraction algorithm is proposed.
Before projecting, we integrated the motor relevant information to suppress the
interference of noise and irrelevant information, as well as to improve the
spatial difference for projection. The algorithm was evaluated with public
datasets. It showed significantly better classification performance with single
trial electroencephalography (EEG) data, increasing by 6.8% compared with the
CSP.
PMID- 28706473
TI - Short-Term Internet-Search Training Is Associated with Increased Fractional
Anisotropy in the Superior Longitudinal Fasciculus in the Parietal Lobe.
AB - The Internet search engine has become an indispensable tool for many people, yet
the ways in which Internet searching may alter brain structure and function is
poorly understood. In this study, we investigated the influence of short-term
Internet-search "training" on white matter microstructure using diffusion tensor
imaging (DTI). Fifty-nine valid subjects (Experimental group, 43; Control group,
16) completed the whole procedure: pre- DTI scan, 6-day's training and post- DTI
scan. Using track-based spatial statistics, we found increased fractional
anisotropy in the right superior longitudinal fasciculus at post-test as compared
to pre-test in experimental group. Within the identified region of the right
superior longitudinal fasciculus, decreased radial diffusivity (RD), and
unchanged axial diffusivity (AD) were observed. These results suggest that short
term Internet-search training may increase white-matter integrity in the right
superior longitudinal fasciculus. A possible mechanism for the observed FA change
may involve increased myelination after training, although this possibility
warrants additional investigation.
PMID- 28706474
TI - Commentary: Parsing the Behavioral and Brain Mechanisms of Third-Party
Punishment.
PMID- 28706475
TI - Focal Stroke in the Developing Rat Motor Cortex Induces Age- and Experience
Dependent Maladaptive Plasticity of Corticospinal System.
AB - Motor system development is characterized by an activity-dependent competition
between ipsilateral and contralateral corticospinal tracts (CST). Clinical
evidence suggests that age is crucial for developmental stroke outcome, with
early lesions inducing a "maladaptive" strengthening of ipsilateral projections
from the healthy hemisphere and worse motor impairment. Here, we investigated in
developing rats the relation between lesion timing, motor outcome and CST
remodeling pattern. We induced a focal ischemia into forelimb motor cortex (fM1)
at two distinct pre-weaning ages: P14 and P21. We compared long-term motor
outcome with changes in axonal sprouting of contralesional CST at red nucleus and
spinal cord level using anterograde tracing. We found that P14 stroke caused a
more severe long-term motor impairment than at P21, and induced a strong and
aberrant contralesional CST sprouting onto denervated spinal cord and red
nucleus. The mistargeted sprouting of CST, and the worse motor outcome of the P14
stroke rats were reversed by an early skilled motor training, underscoring the
potential of early activity-dependent plasticity in modulating lesion outcome.
Thus, changes in the mechanisms controlling CST plasticity occurring during the
third postnatal week are associated with age-dependent regulation of the motor
outcome after stroke.
PMID- 28706476
TI - Long-Term Sex-Dependent Vulnerability to Metabolic challenges in Prenatally
Stressed Rats.
AB - Prenatal stress (PNS) might affect the developmental programming of adult chronic
diseases such as metabolic and mood disorders. The molecular mechanisms
underlying such regulations may rely upon long-term changes in stress-responsive
effectors such as Brain-Derived Neurotrophic Factor (BDNF) that can affect
neuronal plasticity underlying mood disorders and may also play a role in
metabolic regulation. Based upon previous data, we hypothesized that PNS might
lead to greater vulnerability to an obesogenic challenge experienced at
adulthood. In order to investigate our hypothesis, pregnant Sprague-Dawley female
rats underwent a chronic procedure of restraint stress during the last week of
gestation. The adult offspring were then challenged with a high fat diet (HFD)
over 8 weeks and tested for metabolic and emotional endpoints. Moreover, brain
specific changes in Bdnf expression levels were also assessed. Overall, HFD
resulted in increased caloric intake, insulin resistance, impaired glucose
tolerance and higher circulating levels of leptin, while PNS increased the
leptin/adiponectin ratio, an index of metabolic risk in adult male subjects.
Interestingly, HFD consumption increased anxiety-like behaviors in the Elevated
Plus Maze, particularly in males, and this effect was buffered by PNS. Levels of
Bdnf were finely modulated by PNS and HFD in a region- and sex-dependent fashion:
female offspring overall showed greater plasticity, possibly mediated through
increased total Bdnf mRNA expression both in the hippocampus and in the
hypothalamus. In conclusion, while the experience of maternal stress during
intrauterine life promotes metabolic dysfunction induced by a HFD at adulthood,
the interaction between PNS and HFD is positive in male subjects, and in
agreement with the match-mismatch hypothesis, resulting in a reduction of anxious
behaviors.
PMID- 28706477
TI - Response: Commentary: The Brain Basis for Misophonia.
PMID- 28706478
TI - The Effects of Reducing Preparation Time on the Execution of Intentionally Curved
Trajectories: Optimization and Geometrical Analysis.
AB - When subjects are intentionally preparing a curved trajectory, they are engaged
in a time-consuming trajectory planning process that is separate from target
selection. To investigate the construction of such a plan, we examined the effect
of artificially shortening preparation time on the performance of intentionally
curved trajectories using the Timed Response task that enforces initiation of
movements prematurely. Fifteen subjects performed obstacle avoidance movements
toward one of four targets that were presented 25 or 350 ms before the "go"
signal, imposing short and long preparation time conditions with mean values of
170 ms and 493 ms, respectively. While trajectories with short preparation times
showed target specificity at their onset, they were significantly more variable
and showed larger angular deviations from the lines connecting their initial
position and the target, compared to the trajectories with long preparation
times. Importantly, the trajectories of the short preparation time movements
still reached their end-point targets accurately, with comparable movement
durations. We hypothesize that success in the short preparation time condition is
a result of an online control mechanism that allows further refinement of the
plan during its execution and study this control mechanism with a novel
trajectory analysis approach using minimum jerk optimization and geometrical
modeling approaches. Results show a later agreement of the short preparation time
trajectories with the optimal minimum jerk trajectory, accompanied by a later
initiation of a parabolic segment. Both observations are consistent with the
existence of an online trajectory planning process.Our results suggest that when
preparation time is not sufficiently long, subjects execute a more variable and
less optimally prepared initial trajectory and exploit online control mechanisms
to refine their actions on the fly.
PMID- 28706479
TI - Impact of Semantic Relatedness on Associative Memory: An ERP Study.
AB - Encoding and retrieval processes in memory for pairs of pictures are thought to
be influenced by inter-item similarity and by features of individual items. Using
Event-Related Potentials (ERP), we aimed to identify how these processes impact
on both the early mid-frontal FN400 and the Late Positive Component (LPC)
potentials during associative retrieval of pictures. Twenty young adults
undertook a sham task, using an incidental encoding of semantically related and
unrelated pairs of drawings. At test, we conducted a recognition task in which
participants were asked to identify target identical pairs of pictures, which
could be semantically related or unrelated, among new and rearranged pairs. We
observed semantic (related and unrelated pairs) and condition effects (old,
rearranged and new pairs) on the early mid-frontal potential. First, a lower
amplitude was shown for identical and rearranged semantically related pairs,
which might reflect a retrieval process driven by semantic cues. Second, among
semantically unrelated pairs, we found a larger negativity for identical pairs,
compared to rearranged and new ones, suggesting additional retrieval processing
that focuses on associative information. We also observed an LPC old/new effect
with a mid-parietal and a right occipito-parietal topography for semantically
related and unrelated old pairs, demonstrating a recollection phenomenon
irrespective of the degree of association. These findings suggest that
associative recognition using visual stimuli begins at early stages of retrieval,
and differs according to the degree of semantic relatedness among items. However,
either strategy may ultimately lead to recollection processes.
PMID- 28706480
TI - Task Context Influences Brain Activation during Music Listening.
AB - In this paper, we examined brain activation in subjects during two music
listening conditions: listening while simultaneously rating the musical piece
being played [Listening and Rating (LR)] and listening to the musical pieces
unconstrained [Listening (L)]. Using these two conditions, we tested whether the
sequence in which the two conditions were fulfilled influenced the brain
activation observable during the L condition (LR -> L or L -> LR). We recorded
high-density EEG during the playing of four well-known positively experienced
soundtracks in two subject groups. One group started with the L condition and
continued with the LR condition (L -> LR); the second group performed this
experiment in reversed order (LR -> L). We computed from the recorded EEG the
power for different frequency bands (theta, lower alpha, upper alpha, lower beta,
and upper beta). Statistical analysis revealed that the power in all examined
frequency bands increased during the L condition but only when the subjects had
not had previous experience with the LR condition (i.e., L -> LR). For the
subjects who began with the LR condition, there were no power increases during
the L condition. Thus, the previous experience with the LR condition prevented
subjects from developing the particular mental state associated with the typical
power increase in all frequency bands. The subjects without previous experience
of the LR condition listened to the musical pieces in an unconstrained and
undisturbed manner and showed a general power increase in all frequency bands. We
interpret the fact that unconstrained music listening was associated with
increased power in all examined frequency bands as a neural indicator of a mental
state that can best be described as a mind-wandering state during which the
subjects are "drawn into" the music.
PMID- 28706481
TI - Adverse Effects of the Apolipoprotein E epsilon4 Allele on Episodic Memory, Task
Switching and Gray Matter Volume in Healthy Young Adults.
AB - Many studies have shown that healthy elderly subjects and patients with
Alzheimer's disease (AD) who carry the apolipoprotein E (ApoE) epsilon4 allele
have worse cognitive function and more severe brain atrophy than non-carriers.
However, it remains unclear whether this ApoE polymorphism leads to changes of
cognition and brain morphology in healthy young adults. In this study, we used an
established model to measure verbal episodic memory and core executive function
(EF) components (response inhibition, working memory and task switching) in 32
ApoE epsilon4 carriers and 40 non-carriers between 20 years and 40 years of age.
To do this, we carried out an adapted auditory verbal learning test and three
computerized EF tasks. High-resolution head magnetic resonance scans were
performed in all participants and voxel-based morphometry (VBM) was used for
image processing and analysis. Multivariate analysis of variance (ANOVA)
performed on memory measures showed that the overall verbal episodic memory of
ApoE epsilon4 carriers was significantly worse than non-carriers (Wilk's lambda =
4.884, P = 0.004). No significant differences were detected in overall EF between
the two groups. Post hoc analyses revealed group differences in terms of
immediate recall, recognition and task switching, which favored non-carriers. VBM
analysis showed gray matter (GM) bilateral reductions in the medial and
dorsolateral frontal, parietal and left temporal cortices in the carrier group
relative to the non-carrier group, which were most significant in the bilateral
anterior and middle cingulate gyri. However, these changes in GM volume were not
directly associated with changes in cognitive function. Our data show that the
ApoE epsilon4 allele is associated with poorer performance in verbal episodic
memory and task switching, and a reduction in GM volume in healthy young adults,
suggesting that the effects of ApoE epsilon4 upon cognition and brain morphology
exist long before the possible occurrence of AD.
PMID- 28706482
TI - SamuROI, a Python-Based Software Tool for Visualization and Analysis of Dynamic
Time Series Imaging at Multiple Spatial Scales.
AB - The measurement of activity in vivo and in vitro has shifted from electrical to
optical methods. While the indicators for imaging activity have improved
significantly over the last decade, tools for analysing optical data have not
kept pace. Most available analysis tools are limited in their flexibility and
applicability to datasets obtained at different spatial scales. Here, we present
SamuROI (Structured analysis of multiple user-defined ROIs), an open source
Python-based analysis environment for imaging data. SamuROI simplifies
exploratory analysis and visualization of image series of fluorescence changes in
complex structures over time and is readily applicable at different spatial
scales. In this paper, we show the utility of SamuROI in Ca2+-imaging based
applications at three spatial scales: the micro-scale (i.e., sub-cellular
compartments including cell bodies, dendrites and spines); the meso-scale, (i.e.,
whole cell and population imaging with single-cell resolution); and the macro
scale (i.e., imaging of changes in bulk fluorescence in large brain areas,
without cellular resolution). The software described here provides a graphical
user interface for intuitive data exploration and region of interest (ROI)
management that can be used interactively within Jupyter Notebook: a publicly
available interactive Python platform that allows simple integration of our
software with existing tools for automated ROI generation and post-processing, as
well as custom analysis pipelines. SamuROI software, source code and installation
instructions are publicly available on GitHub and documentation is available
online. SamuROI reduces the energy barrier for manual exploration and semi
automated analysis of spatially complex Ca2+ imaging datasets, particularly when
these have been acquired at different spatial scales.
PMID- 28706483
TI - Phytoagent Deoxyelephantopin and Its Derivative Inhibit Triple Negative Breast
Cancer Cell Activity through ROS-Mediated Exosomal Activity and Protein
Functions.
AB - A novel plant sesquiterpene lactone derivative, DET derivative (DETD)-35,
originating from parental deoxyelephantopin (DET) was previously observed to
effectively suppress human triple negative breast cancer (TNBC) MDA-MB-231 cell
activity and tumor growth in mice. In this study, the mechanisms underlying the
activity of DETD-35 were elucidated. DET and DETD-35 induced reactive oxygen
species (ROS) which caused structural damage and dysfunction of mitochondria and
increased cytosolic calcium level, subsequently evoking exosome release from the
cancer cells. Intriguingly, exosomes induced by both compounds had an atypical
function. Cancer cell-derived exosomes commonly show metastatic potential, but
upon DET/DETD-35 treatment exosomes showed anti-proliferative activity against
MDA-MB-231 cells. Quantitative proteome analysis of TNBC cell-secreted exosomes
showed that DET and DETD-35 attenuated the expression of proteins related to cell
migration, cell adhesion, and angiogenesis. Furthermore, several exosomal
proteins participating in biological mechanisms such as oxidative stress and
decrease of transmembrane potential of mitochondria were found deregulated by
treatment with either compound. Pretreatment with ROS scavenger, N
acetylcysteine, blockaded DET- or DETD-35-induced oxidative stress and calcium
dependent exosome release mechanisms, and also reverted DET- or DETD-35-induced
reprogramming exosomal protein expression profiles resulting in attenuation of
exosomal toxicity against TNBC cell proliferation. In summary, this study shows
that a plant-derived sesquiterpene lactone DET and its analog DETD-35 inhibitory
TNBC cell activities through oxidative stress-induced cancer cell releasing
exosomes in tandem with alteration of exosomal protein composition and functions.
The findings of this study suggest that DETD-35 may be suitable for further
development into an anti-TNBC drug.
PMID- 28706484
TI - Alantolactone Improves Prolonged Exposure of Interleukin-6-Induced Skeletal
Muscle Inflammation Associated Glucose Intolerance and Insulin Resistance.
AB - The pro-inflammatory cytokine, Interleukin-6 (IL-6), has been proposed to be one
of the mediators that link chronic inflammation to glucose intolerance and
insulin resistance. Many studies have demonstrated the effects of IL-6 on insulin
action in the skeletal muscle. However, few studies have investigated the effect
of long-term treatment of IL-6, leading to glucose intolerance and insulin
resistance. In the present study, we observed protective effects of
alantolactone, a sesquiterpene lactone isolated from Inula helenium against
glucose intolerance and insulin resistance induced by prolonged exposure of IL-6.
Alantolactone has been reported to have anti-inflammatory and anti-cancer effects
through IL-6-induced signal transducer and activator of transcription 3 (STAT3)
signaling pathway. The relationship between IL-6 exposure and expression of toll
like receptor 4 (TLR4), involved in inflammation in the skeletal muscle, and the
underlying mechanisms were investigated. We observed maximum dysregulation of
glucose uptake after 40 ng/ml IL-6 induction for 24 h in L6 myotubes. Prolonged
IL-6 exposure suppressed glucose uptake regulating alpha serine/threonine-protein
kinase (AKT) phosphorylation; however, pretreatment with alantolactone activated
AKT phosphorylation and improved glucose uptake. Alantolactone also attenuated IL
6-stimulated STAT3 phosphorylation, followed by an increase in expression of
negative regulator suppressor of cytokine signaling 3 (SOCS3). Furthermore, IL-6
induced expression of pathogen recognition receptor, TLR4, was also suppressed by
alantolactone pretreatment. Post-silencing of STAT3 using siRNA approach, IL-6
stimulated siRNA-STAT3 improved glucose uptake and suppressed TLR4 gene
expression. Taken together, we propose that, as a STAT3 inhibitor, alantolactone,
improves glucose regulation in the skeletal muscle by inhibiting IL-6-induced
STAT3-SOCS3 signaling followed by inhibition of the TLR4 gene expression.
Therefore, alantolactone can be a promising candidate for the treatment of
inflammation-associated glucose intolerance and insulin resistance.
PMID- 28706485
TI - The Combination of Rituximab and Bendamustine as First-Line Treatment Is Highly
Effective in the Eradicating Minimal Residual Disease in Follicular Lymphoma: An
Italian Retrospective Study.
AB - R-Bendamustine is an effective treatment for follicular lymphoma (FL). Previous
large trials demonstrated the prognostic role of the molecular minimal residual
disease (MRD) during the most frequently adopted chemotherapeutic regimens, but
there are not yet conclusive data about the effect of combination of rituximab
(R) and bendamustine in terms of MRD clearance. Thus, the aim of this
retrospective study was to assess if and in what extent the combination of
rituximab and bendamustine would exert a significant reduction of the molecular
disease in 48 previously untreated FL patients. The molecular marker at baseline
was found in the 62.5% of cases; no significant differences were observed between
patients with or without the molecular marker in respect of the main clinical
features. Moreover, the quantization of the baseline molecular tumor burden
showed a great variability: the median value was 1.4 * 10-2 copies, ranging from
3 * 10-5 to 4 * 104. The initial molecular tumor burden did not correlate with
clinical features and did not impact on the subsequent quality of response. After
treatment, 93% of cases became MRD-negative; the median reduction of the BCL2/JH
load was 4 logs. The 2-years PFS was 85%; it was significantly longer for
patients in complete than for those in partial response (91 vs. 57%; p = 0.002),
and for cases with lower FLIPI-2 score (88 vs. 60%; p = 0.004). On the contrary,
PFS did not differ between patients with or without the molecular marker at
baseline; a molecular tumor burden 15 times higher was observed in the relapsed
subgroup in comparison to the relapse-free one, but this difference did not
change the PFS length. The 2-years OS was 93.6%; the only variable that
significantly impacted on it was the FLIPI-2 score; the presence of the molecular
marker at baseline or its behavior after treatment did not impact on survival.
This study, even if retrospective and conducted on a small series of patients,
would represent a proof of concept that R-bendamustine is able to so
efficaciously eradicate MRD that it could be able to by-pass the prognostic
significance of MRD already demonstrated for other chemotherapeutic regimens in
FL.
PMID- 28706486
TI - Observed and Normative Discount Functions in Addiction and other Diseases.
AB - The aim of this paper is to find a suitable discount function able to describe
the progression of a certain addiction or disease under treatment as a
discounting process. In effect, a certain indicator related to a disease decays
over time in a manner which is mathematically similar to the way in which
discounting has been modeled. We analyze the discount functions observed in
experiments which study addictive and other problematic behaviors as well as some
alternative hyperbola-like discount functions in order to fit the patience
exhibited by the subject after receiving the treatment. Additionally, it has been
experimentally found that people with addiction display high rates of discount
(impatience) and preference reversals (dynamic inconsistency). This excessive
discounting must be correctly modeled by a suitable discount function, otherwise,
it can become a trans-disease process underlying addiction and other disorders.
The (generalized) exponentiated hyperbolic discount function is proposed to
describe the progression of a disease with respect to the treatment, since it
maintains the property of inconsistency by exhibiting a decreasing discount rate
after an initial period in which the opposite occurs.
PMID- 28706487
TI - Pekinenin E Inhibits the Growth of Hepatocellular Carcinoma by Promoting
Endoplasmic Reticulum Stress Mediated Cell Death.
AB - Hepatocellular carcinoma (HCC) is a malignant primary liver cancer with poor
prognosis. In the present study, we report that pekinenin E (PE), a casbane
diterpenoid derived from the roots of Euphorbia pekinensis, has a strong
antitumor activity against human HCC cells both in vitro and in vivo. PE
suppressed the growth of human HCC cells Hep G2 and SMMC-7721. In addition, PE
mediated endoplasmic reticulum (ER) stress caused increasing expressions of C/EBP
homologous protein (CHOP), leading to apoptosis in HCC cells both in vitro and in
vivo. Inhibition of ER stress with CHOP small interfering RNA or 4-phenyl-butyric
acid partially reversed PE-induced cell death. Furthermore, PE induced S cell
cycle arrest, which could also be partially reversed by CHOP knockdown. In all,
these findings suggest that PE causes ER stress-associated cell death and cell
cycle arrest, and it may serve as a potent agent for curing human HCC.
PMID- 28706488
TI - Postnatal Maturation of the Glomerular Filtration Rate in Conventional Growing
Piglets As Potential Juvenile Animal Model for Preclinical Pharmaceutical
Research.
AB - Adequate animal models are required to study the preclinical pharmacokinetics
(PK), pharmacodynamics (PD) and safety of drugs in the pediatric subpopulation.
Over the years, pigs were presented as a potential animal model, since they
display a high degree of anatomical and physiological similarities with humans.
To assess the suitability of piglets as a preclinical animal model for children,
the ontogeny and maturation processes of several organ systems have to be
unraveled and compared between both species. The kidneys play a pivotal role in
the PK and PD of various drugs, therefore, the glomerular filtration rate (GFR)
measured as clearance of endogenous creatinine (Jaffe and enzymatic assay) and
exo-iohexol was determined in conventional piglets aging 8 days (n = 16), 4 weeks
(n = 8) and 7 weeks (n = 16). The GFR data were normalized to bodyweight (BW),
body surface area (BSA) and kidney weight (KW). Normalization to BSA and KW
showed an increase in GFR from 46.57 to 100.92 mL/min/m2 and 0.49 to 1.51
mL/min/g KW from 8 days to 7 weeks of age, respectively. Normalization to BW
showed a less pronounced increase from 3.55 to 4.31 mL/min/kg. The postnatal
development of the GFR was comparable with humans, rendering the piglet a
convenient juvenile animal model for studying the PK, PD and safety of drugs in
the pediatric subpopulation. Moreover, to facilitate the assessment of the GFR in
growing piglets in subsequent studies, a formula was elaborated to estimate the
GFR based on plasma creatinine and BW, namely eGFR =1.879 * BW1.092[Formula: see
text].
PMID- 28706489
TI - Difference in Striae Periodicity of Heilongjiang and Singaporean Chinese Teeth.
AB - Striae periodicity refers to the number of cross-striations between successive
lines of Retzius in tooth enamel. A regular time dependency of striae
periodicity, known as the circaseptan interval, has been proposed. Previous
studies on striae periodicity have been carried out on both modern and early
humans given its potential applications in forensic age estimations and
anthropology. Nevertheless, research comparing striae periodicities across gender
groups and populations in different geographical locations, particularly in Asia,
is lacking. In this study, we compared the striae periodicities of Heilongjiang
and Singaporean Chinese, as well as that of Singaporean Chinese males and
females. Results showed that while the median striae periodicity counts of
Heilongjiang Chinese and Singaporean Chinese teeth are both 7, Heilongjiang
Chinese tend to have lower striae periodicity counts than Singaporean Chinese (p
< 0.01). No significant gender difference was observed between the median striae
periodicity of Singaporean Chinese Female and Singaporean Chinese Male teeth (p =
0.511). We concluded that the median striae periodicity may statistically differ
with geographical location, but not gender, provided that ethnicity and
geographical location are held constant. Further studies are required to examine
the causes for variation in striae periodicities between geographical locations,
as well as to verify the other bio-environmental determinants of striae
periodicity.
PMID- 28706490
TI - Effects of 6-Weeks High-Intensity Interval Training in Schoolchildren with
Insulin Resistance: Influence of Biological Maturation on Metabolic, Body
Composition, Cardiovascular and Performance Non-responses.
AB - Background: Previous studies have observed significant heterogeneity in the
magnitude of change in measures of metabolic response to exercise training. There
are a lack of studies examining the prevalence of non-responders (NRs) in
children while considering other potential environmental factors involved such as
biological maturation. Aim: To compare the effects and prevalence of NRs to
improve the insulin resistance level (by HOMA-IR), as well as to other
anthropometric, cardiovascular, and performance co-variables, between early (EM)
and normal maturation (NM) in insulin-resistance schoolchildren after 6-weeks of
HIIT. Methods: Sedentary children (age 11.4 +/- 1.7 years) were randomized to
either HIIT-EM group (n = 12) or HIIT-NM group (n = 17). Fasting glucose (FGL),
fasting insulin (FINS) and homeostasis model assessment of insulin resistant
(HOMA-IR) were assessed as the main outcomes, as well as the body composition
[body mass, body mass index (BMI), waist circumference (WC), and tricipital
(TSF), suprailiac (SSF) and abdominal skinfold (AbdSF)], cardiovascular systolic
(SBP) and diastolic blood pressure (DBP), and muscular performance [one
repetition maximum strength leg-extension (1RMLE) and upper row (1RMUR) tests] co
variables were assessed before and after intervention. Responders or NRs to
training were defined as a change in the typical error method from baseline to
follow-up for the main outcomes and co-variables. Results: There were no
significant differences between groups in the prevalence of NRs based on FGL,
FINS, and HOMA-IR. There were significant differences in NRs prevalence to
decrease co-variables body mass (HIIT-EM 66.6% vs. HIIT-NM 35.2%) and SBP (HIIT
EM 41.6% vs. HIIT-NM 70.5%). A high risk [based on odds ratios (OR)] of NRs cases
was detected for FGL, OR = 3.2 (0.2 to 5.6), and HOMA-IR, OR = 3.2 (0.2 to 6.0).
Additionally, both HIIT-EM and HIIT-NM groups showed significant decreases (P <
0.05) in TSF, SSF, and AbdSF skinfold, and similar decreases in fasting insulin
and HOMA-IR. The HIIT-EM group showed significant decreases in SBP. The HIIT-NM
group showed significant increases in 1RMLE and 1RMUR. A large effect size was
observed for pre-post changes in TSF in both groups, as well as in SSF in the
HIIT-NM group. Conclusion: Although there were no differences in the prevalence
of NRs to metabolic variables between groups of insulin resistance schoolchildren
of different maturation starting, other NRs differences were found to body mass
and systolic BP, suggesting that anthropometric and cardiovascular parameters can
be playing a role in the NRs prevalence after HIIT. These results were displayed
with several metabolic, body composition, blood pressure, and performance
improvements independent of an early/normal maturation or the prevalence of NRs.
PMID- 28706491
TI - Early-Life Exposure to Lead Induces Cognitive Impairment in Elder Mice Targeting
SIRT1 Phosphorylation and Oxidative Alterations.
AB - Pb is a potential risk factor for cognition, mainly mediated by enhanced
oxidative stress. Resveratrol, a natural polyphenol with crucial anti-oxidative
property, is recently implicated in preventing cognitive deficits in normal aging
and neurodegenerative disorders. Its beneficial effects have been linked to
sirtuin 1(SIRT1) activation. The aim of this work is to investigate the possible
linkage between alterations in Pb-induced oxidative damage and cognitive
impairment by prolonged treatment of resveratrol. Male C57BL/6 mice were given
Pb(Ac)2 treatment or deionized H2O for 12 weeks, and subjected to resveratrol
gavage at the dose of 50 mg/kgBw*d or vehicle after Pb exposure. Results from
biochemical analysis and immunohistofluorescence showed that Pb induced oxidative
DNA damage and decreased cortical antioxidant biomarker. As expected, these
abnormalities were improved by resveratrol treatment. Morris water maze test,
Western blotting, immunohistofluorescence staining and RT-qPCR indicated that
resveratrol ameliorated spatial learning and memory deficits with alterations in
hippocampal BDNF-TrkB signaling, promoted nuclear localization and
phosphorylation of hippocampal SIRT1, partly increased protein levels of AMPK and
PGC-1alpha involving in modulation of antioxidant response in Pb-exposed mice.
Our results support the hypothesis that resveratrol could attenuate Pb-induced
cognitive impairment which was associated with activating SIRT1 via modulation of
oxidative stress. Additionally, resveratrol also repressed the Pb-induce
amyloidogenic processing with resultant decline in cortical Abeta1--40.
Noteworthy, such effects were not mediated by resveratrol treatment alone. These
findings emphasize the potential of SIRT1 activator as an efficacious dietary
intervention to downgrade the Pb-induced neurotoxic lesion.
PMID- 28706492
TI - Lower Expression of SLC27A1 Enhances Intramuscular Fat Deposition in Chicken via
Down-Regulated Fatty Acid Oxidation Mediated by CPT1A.
AB - Intramuscular fat (IMF) is recognized as the predominant factor affecting meat
quality due to its positive correlation with tenderness, juiciness, and flavor.
Chicken IMF deposition depends on the balance among lipid synthesis, transport,
uptake, and subsequent metabolism, involving a lot of genes and pathways,
however, its precise molecular mechanisms remain poorly understood. In the
present study, the breast muscle tissue of female Wenchang chickens (WC) (higher
IMF content, 1.24 in D120 and 1.62 in D180) and female White Recessive Rock
chickens (WRR; lower IMF content, 0.53 in D120 and 0.90 in D180) were subjected
to RNA-sequencing (RNA-seq) analysis. Results showed that many genes related to
lipid catabolism, such as SLC27A1, LPL, ABCA1, and CPT1A were down-regulated in
WC chickens, and these genes were involved in the PPAR signaling pathway and
formed an IPA(r) network related to lipid metabolism. Furthermore, SLC27A1 was
more down-regulated in WRR.D180.B than in WRR.D120.B. Decreased cellular
triglyceride (TG) and up-regulated CPT1A were observed in the SLC27A1
overexpression QM-7 cells, and increased cellular triglyceride (TG) and down
regulated CPT1A were observed in the SLC27A1 knockdown QM-7 cells. These results
suggest that lower lipid catabolism exists in WC chickens but not in WRR
chickens, and lower expression of SLC27A1 facilitate IMF deposition in chicken
via down-regulated fatty acid oxidation mediated by CPT1A. These findings
indicate that reduced lipid catabolism, rather than increased lipid anabolism,
contributes to chicken IMF deposition.
PMID- 28706493
TI - Protein Phosphorylation and Mineral Binding Affect the Secondary Structure of the
Leucine-Rich Amelogenin Peptide.
AB - Previously, we have shown that serine-16 phosphorylation in native full-length
porcine amelogenin (P173) and the Leucine-Rich Amelogenin Peptide (LRAP(+P)), an
alternative amelogenin splice product, affects protein assembly and
mineralization in vitro. Notably, P173 and LRAP(+P) stabilize amorphous calcium
phosphate (ACP) and inhibit hydroxyapatite (HA) formation, while non
phosphorylated counterparts (rP172, LRAP(-P)) guide the growth of ordered bundles
of HA crystals. Based on these findings, we hypothesize that the phosphorylation
of full-length amelogenin and LRAP induces conformational changes that critically
affect its capacity to interact with forming calcium phosphate mineral phases. To
test this hypothesis, we have utilized Fourier transform infrared spectroscopy
(FTIR) to determine the secondary structure of LRAP(-P) and LRAP(+P) in the
absence/presence of calcium and selected mineral phases relevant to amelogenesis;
i.e., hydroxyapatite (HA: an enamel crystal prototype) and (ACP: an enamel
crystal precursor phase). Aqueous solutions of LRAP(-P) or LRAP(+P) were prepared
with or without 7.5 mM of CaCl2 at pH 7.4. FTIR spectra of each solution were
obtained using attenuated total reflectance, and amide-I peaks were analyzed to
provide secondary structure information. Secondary structures of LRAP(+P) and
LRAP(-P) were similarly assessed following incubation with suspensions of HA and
pyrophosphate-stabilized ACP. Amide I spectra of LRAP(-P) and LRAP(+P) were found
to be distinct from each other in all cases. Spectra analyses showed that LRAP(
P) is comprised mostly of random coil and beta-sheet, while LRAP(+P) exhibits
more beta-sheet and alpha-helix with little random coil. With added Ca, the
random coil content increased in LRAP(-P), while LRAP(+P) exhibited a decrease in
alpha-helix components. Incubation of LRAP(-P) with HA or ACP resulted in
comparable increases in beta-sheet structure. Notably, however, LRAP(+P)
secondary structure was more affected by ACP, primarily showing an increase in
beta-sheet structure, compared to that observed with added HA. These collective
findings indicate that phosphorylation induces unique secondary structural
changes that may enhance the functional capacity of native phosphorylated
amelogenins like LRAP to stabilize an ACP precursor phase during early stages of
enamel mineral formation.
PMID- 28706494
TI - RNA-Sequencing Analyses Demonstrate the Involvement of Canonical Transient
Receptor Potential Channels in Rat Tooth Germ Development.
AB - Tooth development depends on multiple molecular interactions between the dental
epithelium and mesenchyme, which are derived from ectodermal and ectomesenchymal
cells, respectively. We report on a systematic RNA sequencing analysis of
transcriptional expression levels from the bud to hard tissue formation stages of
rat tooth germ development. We found that GNAO1, ENO1, EFNB1, CALM1, SIAH2,
ATP6V0A1, KDELR2, GTPBP1, POLR2C, SORT1, and members of the canonical transient
receptor potential (TRPC) channel family are involved in tooth germ development.
Furthermore, Cell Counting Kit 8 (CCK8) and Transwell migration assays were
performed to explore the effects of these differentially expressed genes (DEGs)
on the proliferation and migration of dental pulp stem cells. Immunostaining
revealed that TRPC channels are expressed at varying levels during odontogenesis.
The identified genes represent novel candidates that are likely to be vital for
rat tooth germ development. Together, the results provide a valuable resource to
elucidate the gene regulatory mechanisms underlying mammalian tooth germ
development.
PMID- 28706495
TI - Emotional Support, Depressive Symptoms, and Age-Related Alterations in Male Body
Composition: Cross-Sectional Findings from the Men's Health 40+ Study.
AB - More depressive symptoms and low emotional support have been related to worse
body composition. Body composition significantly deteriorates in aging men.
Therefore, we aimed to examine whether high emotional support and low depressive
symptoms are associated with better body composition and a decelerated age
related deterioration of body composition in aging men. A cross-sectional
analysis including 269 self-reporting healthy men aged between 40 and 75 years
living in the German-speaking part of Switzerland was conducted. Participants
completed questionnaires on emotional support and depressive symptoms. The
depression screening instrument was used to form a group with low (N = 225) and
moderate (N = 44) depressive symptoms. Body mass index (BMI) and waist-to-hip
ratio (WHR) were measured, and cell proportion (CP), fat mass (FM), and water
balance (WB) were obtained using bioelectrical impedance analysis. Age-related
associations emerged for WHR, CP, FM, and WB, but not for BMI. Emotional support
was negatively associated with BMI, WHR, and WB, and only trend-wise with CP and
FM. Group comparisons revealed that more depressive symptoms were associated with
lower levels of CP and higher levels of WB. Both emotional support and depressive
symptoms were significant moderators of the association between age and specific
measures of body composition such as CP, FM, and WB. However, after correction
for multiple testing for moderation analyses only the moderation effects of
depressive symptoms on the association between age and WB and CP remained
significant. Low depressive symptoms were associated with a better body
composition as well as a decelerated decline in body composition and the role of
emotional support acting as a buffer against age-related deterioration of body
composition merits further investigation.
PMID- 28706496
TI - The Mediation Effect of Coping Style on the Relations between Personality and
Life Satisfaction in Chinese Adolescents.
AB - Previous findings showed the associations between each of the Big Five
personality trait and adolescents' life satisfaction were different. Some traits
(extraversion and neuroticism) correlated with adolescents' life satisfaction,
while other traits did not have the same associations with adolescents' life
satisfaction. In order to explain why the Big Five traits differed in their
associations with adolescents' life satisfaction, the present study verified the
relations between each of the Big Five personality traits and life satisfaction,
and demonstrated the mediating effects of coping style on the relations between
these personality traits and life satisfaction in a sample of 2,357 Chinese
adolescents. The results demonstrated that four of the Big Five personality
traits (extraversion, agreeableness, conscientiousness, and neuroticism) had
significant associations with life satisfaction. Further, coping style partially
mediated the relations between these four traits and life satisfaction, whereas
coping style fully mediated the relation between openness to new experience and
life satisfaction. The results implied a plausible explanation for why the Big
Five traits differed in their associations with life satisfaction found among the
previous literature: that there might be some partial or full mediation variables
(such as coping style in this study) left unexamined. Theoretical and practical
implications of this study on further research and educational practice are
discussed.
PMID- 28706497
TI - The Sustained Influence of an Error on Future Decision-Making.
AB - Post-error slowing (PES) is consistently observed in decision-making tasks after
negative feedback. Yet, findings are inconclusive as to whether PES supports
performance accuracy. We addressed the role of PES by employing drift diffusion
modeling which enabled us to investigate latent processes of reaction times and
accuracy on a large-scale dataset (>5,800 participants) of a visual search
experiment with emotional face stimuli. In our experiment, post-error trials were
characterized by both adaptive and non-adaptive decision processes. An adaptive
increase in participants' response threshold was sustained over several trials
post-error. Contrarily, an initial decrease in evidence accumulation rate,
followed by an increase on the subsequent trials, indicates a momentary
distraction of task-relevant attention and resulted in an initial accuracy drop.
Higher values of decision threshold and evidence accumulation on the post-error
trial were associated with higher accuracy on subsequent trials which further
gives credence to these parameters' role in post-error adaptation. Finally, the
evidence accumulation rate post-error decreased when the error trial presented
angry faces, a finding suggesting that the post-error decision can be influenced
by the error context. In conclusion, we demonstrate that error-related response
adaptations are multi-component processes that change dynamically over several
trials post-error.
PMID- 28706498
TI - Editorial: Eastern Philosophies and Psychology: Towards Psychology of Self
Cultivation.
PMID- 28706499
TI - Valence-Dependent Belief Updating: Computational Validation.
AB - People tend to update beliefs about their future outcomes in a valence-dependent
way: they are likely to incorporate good news and to neglect bad news. However,
belief formation is a complex process which depends not only on motivational
factors such as the desire for favorable conclusions, but also on multiple
cognitive variables such as prior beliefs, knowledge about personal
vulnerabilities and resources, and the size of the probabilities and estimation
errors. Thus, we applied computational modeling in order to test for valence
induced biases in updating while formally controlling for relevant cognitive
factors. We compared biased and unbiased Bayesian models of belief updating, and
specified alternative models based on reinforcement learning. The experiment
consisted of 80 trials with 80 different adverse future life events. In each
trial, participants estimated the base rate of one of these events and estimated
their own risk of experiencing the event before and after being confronted with
the actual base rate. Belief updates corresponded to the difference between the
two self-risk estimates. Valence-dependent updating was assessed by comparing
trials with good news (better-than-expected base rates) with trials with bad news
(worse-than-expected base rates). After receiving bad relative to good news,
participants' updates were smaller and deviated more strongly from rational
Bayesian predictions, indicating a valence-induced bias. Model comparison
revealed that the biased (i.e., optimistic) Bayesian model of belief updating
better accounted for data than the unbiased (i.e., rational) Bayesian model,
confirming that the valence of the new information influenced the amount of
updating. Moreover, alternative computational modeling based on reinforcement
learning demonstrated higher learning rates for good than for bad news, as well
as a moderating role of personal knowledge. Finally, in this specific
experimental context, the approach based on reinforcement learning was superior
to the Bayesian approach. The computational validation of valence-dependent
belief updating represents a novel support for a genuine optimism bias in human
belief formation. Moreover, the precise control of relevant cognitive variables
justifies the conclusion that the motivation to adopt the most favorable self
referential conclusions biases human judgments.
PMID- 28706500
TI - Executive Functions Do Not Mediate Prospective Relations between Indices of
Physical Activity and Academic Performance: The Active Smarter Kids (ASK) Study.
AB - Changes in cognitive function induced by physical activity have been proposed as
a mechanism for the link between physical activity and academic performance. The
aim of this study was to investigate if executive function mediated the
prospective relations between indices of physical activity and academic
performance in a sample of 10-year-old Norwegian children. The study included
1,129 children participating in the Active Smarter Kids (ASK) trial, followed
over 7 months. Structural equation modeling (SEM) with a latent variable of
executive function (measuring inhibition, working memory, and cognitive
flexibility) was used in the analyses. Predictors were objectively measured
physical activity, time spent sedentary, aerobic fitness, and motor skills.
Outcomes were performance on national tests of numeracy, reading, and English (as
a second language). Generally, indices of physical activity did not predict
executive function and academic performance. A modest mediation effect of
executive function was observed for the relation between motor skills and
academic performance. Trial registration: Clinicaltrials.gov registry, trial
registration number: NCT02132494.
PMID- 28706501
TI - Bridges or Barriers? Conceptualization of the Role of Multiple Identity Gateway
Groups in Intergroup Relations.
AB - The modern era of globalization has been accompanied by a massive growth in
interconnections between groups, and has led to the sharing of multiple
identities by individuals and groups. Following these developments, research has
focused on the issue of multiple identities, and has shed important light on how
individuals who hold these complex forms of identity feel and behave, and on the
reactions they elicit from members of other groups. However, the potential of
groups with such multiple identities (e.g., biracials, immigrants, etc.) to
affect the intergroup relations between the groups that represent the respective
sources of the different identities (e.g., Blacks and Whites, country of origin
and country of residence, etc.) has not been examined to date. Accordingly, in
this paper, we first systematically explore the potential of groups in which
people identify with multiple social categories, or groups that are perceived as
such by others, to play a role in intergroup dynamics. Next, we offer a
theoretical framework outlining what functions groups of people with shared
multiple identities may serve (as bridges or barriers) by proposing how their
presence may facilitate or deteriorate intergroup relations. Finally, we present
recent empirical research examining how groups of people with shared multiple
identities can act as gateways and bridge the cleft between two separate groups
that represent the respective sources of their different identities, and discuss
the theoretical and practical implications for the field of intergroup relations.
PMID- 28706502
TI - Editorial: The Role of Play in Child Assessment and Intervention.
PMID- 28706503
TI - Parental Post-traumatic Stress Disorder Symptoms Are Related to Successful Aging
in Offspring of Holocaust Survivors.
AB - A fascinating, yet underexplored, question is whether traumatic events
experienced by previous generations affect the aging process of subsequent
generations. This question is especially relevant for offspring of Holocaust
survivors (OHS), who begin to face the aging process. Some preliminary findings
point to greater physical dysfunction among middle-aged OHS, yet the mechanisms
behind this dysfunction need further clarification. Therefore, the current
studies assess aging OHS using the broad-scoped conceptualization of successful
aging, while examining whether offspring successful aging relates to parental
post-traumatic stress disorder (PTSD) symptoms and offspring's secondary
traumatization symptoms. In Study 1, 101 adult offspring (mean age = 62.31)
completed measures of parental PTSD, secondary traumatization, as well as
successful aging indices - objective (medical conditions, disability and somatic
symptoms) and subjective (perceptions of one's aging). Relative to comparisons
and OHS who reported that none of their parents suffered from probable PTSD, OHS
who reported that their parents suffered from probable PTSD had lower scores in
objective and subjective measures of successful aging. Mediation analyses showed
that higher level of secondary traumatization mediated the relationship between
parental PTSD and less successful aging in the offspring. Study 2 included 154
dyads of parents (mean age = 81.86) and their adult offspring (mean age = 54.48).
Parents reported PTSD symptoms and offspring reported secondary traumatization
and completed measures of objective successful aging. Relative to comparisons,
OHS whose parent had probable PTSD have aged less successfully. Once again,
offspring secondary traumatization mediated the effect. The findings suggest that
parental post-traumatic reactions assessed both by offspring (Study 1) and by
parents themselves (Study 2) take part in shaping the aging of the subsequent
generation via reactions of secondary traumatization in the offspring. The
studies also provide initial evidence that these processes can transpire even
when offspring do not have probable PTSD or when controlling offspring anxiety
symptoms. Our findings allude to additional behavioral and epigenetic processes
that are potentially involved in the effect of parental PTSD on offspring aging,
and further imply the need to develop interdisciplinary interventions aiming at
promoting successful aging among offspring of traumatized parents.
PMID- 28706504
TI - Hypertrophic Olivary Degeneration and Palatal or Oculopalatal Tremor.
AB - Hypertrophic degeneration of the inferior olive is mainly observed in patients
developing palatal tremor (PT) or oculopalatal tremor (OPT). This syndrome
manifests as a synchronous tremor of the palate (PT) and/or eyes (OPT) that may
also involve other muscles from the branchial arches. It is associated with
hypertrophic inferior olivary degeneration that is characterized by enlarged and
vacuolated neurons, increased number and size of astrocytes, severe fibrillary
gliosis, and demyelination. It appears on MRI as an increased T2/FLAIR signal
intensity and enlargement of the inferior olive. There are two main conditions in
which hypertrophic degeneration of the inferior olive occurs. The most frequent,
studied, and reported condition is the development of PT/OPT and hypertrophic
degeneration of the inferior olive in the weeks or months following a structural
brainstem or cerebellar lesion. This "symptomatic" condition requires a
destructive lesion in the Guillain-Mollaret pathway, which spans from the
contralateral dentate nucleus via the brachium conjunctivum and the ipsilateral
central tegmental tract innervating the inferior olive. The most frequent
etiologies of destructive lesion are stroke (hemorrhagic more often than
ischemic), brain trauma, brainstem tumors, and surgical or gamma knife treatment
of brainstem cavernoma. The most accepted explanation for this symptomatic PT/OPT
is that denervated olivary neurons released from inhibitory inputs enlarge and
develop sustained synchronized oscillations. The cerebellum then
modulates/accentuates this signal resulting in abnormal motor output in the
branchial arches. In a second condition, PT/OPT and progressive cerebellar ataxia
occurs in patients without structural brainstem or cerebellar lesion, other than
cerebellar atrophy. This syndrome of progressive ataxia and palatal tremor may be
sporadic or familial. In the familial form, where hypertrophic degeneration of
the inferior olive may not occur (or not reported), the main reported etiologies
are Alexander disease, polymerase gamma mutation, and spinocerebellar ataxia type
20. Whether or not these are associated with specific degeneration of the dentato
olivary pathway remain to be determined. The most symptomatic consequence of OPT
is eye oscillations. Therapeutic trials suggest gabapentin or memantine as
valuable drugs to treat eye oscillations in OPT.
PMID- 28706505
TI - Cell-Cell Interaction Proteins (Gap Junctions, Tight Junctions, and Desmosomes)
and Water Transporter Aquaporin 4 in Meningothelial Cells of the Human Optic
Nerve.
AB - PURPOSE: Meningothelial cells (MECs) play a central role in the maintenance of
cerebrospinal fluid (CSF) homeostasis and in physiological and pathophysiological
processes within the subarachnoid space (SAS) linking them to optic nerve (ON)
pathologies. Still, not much is known about their structural properties that
might enable MECs to perform specific functions within the ON microenvironment.
METHODS: For closer characterization of the structural properties of the human
MEC layer in the arachnoid, we performed immunohistological analyses to evaluate
the presence of cell-cell interaction markers, namely, markers for tight
junctions (JAM1, Occludin, and Claudin 5), gap junctions (Connexin 26 and 43),
and desmosomes (Desmoplakin) as well as for water channel marker aquaporin 4
(AQP4) in retrobulbar, midorbital, and intracanalicular human ON sections.
RESULTS: MECs displayed immunopositivity for markers of tight junctions (JAM1,
Occludin, and Claudin 5) and gap junctions (Connexin 26 and 43) as well as for
AQP4 water channels. However, no immunopositivity was found for Desmoplakin.
CONCLUSION: MECs are connected via tight junctions and gap junctions, and they
possess AQP4 water channels. The presence of these proteins emphasizes the
important function of MECs within the ON microenvironment as part of the
meningeal barrier. Beyond this barrier function, the expression of these proteins
by MECs supports a broader role of these cells in signal transduction and CSF
clearance pathways within the ON microenvironment.
PMID- 28706506
TI - Identification of BRCA1 As a Potential Biomarker for Insulin-Like Growth Factor-1
Receptor Targeted Therapy in Breast Cancer.
AB - The insulin-like growth factor-1 receptor (IGF1R) emerged in recent years as a
promising therapeutic target in oncology. Identification of potential biomarkers
capable of predicting response to IGF1R-targeted therapy is of cardinal
importance. Tumor suppressor BRCA1 has important roles in multiple pathways,
including gene transcription, DNA damage repair, and control of apoptosis. Early
studies have identified the IGF1R gene as a downstream target for inhibitory
regulation by wild-type, but not mutant, BRCA1. The aim of the present study was
to evaluate the hypothesis that the mutational status of BRCA1 may influence the
ability of IGF1R-directed therapies to efficiently inhibit the IGF1R axis. Using
breast cancer-derived cell lines expressing a wild-type or a mutant BRCA1, we
demonstrate that the capacity of MK-0646, a monoclonal antibody antagonist to the
human IGF1R, to inhibit insulin-like growth factor-1-stimulated IGF1R and
downstream mediators' phosphorylation was impaired in mutant BRCA1-expressing
cell lines. In addition, the antibody was able to reduce proliferation of wild
type BRCA1-expressing cells but had a reduced inhibitory effect in mutant BRCA1
expressing cells. In summary, our data indicate that the mutational status of
BRCA1 must be taken into account when selecting patients for IGF1R targeting
protocols.
PMID- 28706507
TI - Epigenetics and Autoimmune Thyroid Diseases.
AB - Increasing evidence suggests that epigenetic modifications, including changes in
DNA methylation, covalent modifications of histone tails, and gene silencing
mediated by non-coding RNA molecules, play a substantial role in the pathogenesis
of autoimmune disorders and might be seen as the result of environmental insults
that trigger these conditions. Studies in cells and tissues of patients with
autoimmune thyroid diseases (AITD), and particularly in Graves' disease (GD) and
Hashimoto's thyroiditis (HT), are increasingly revealing altered epigenetic marks
and resultant deregulation of gene expression levels, but the available data are
still limited to be translated into the clinical settings. Particularly, genome
wide methylation and histone tail modification screenings are limited to a few
studies in GD patients, and the diagnostic values of the observed epigenetic
changes or their potential prognostic utility are still unclear. Similarly, data
concerning microRNA expression in AITD patients are largely descriptive and not
yet translated into the clinics. In addition, studies relating certain
environmental exposures to specific epigenetic changes in AITD and studies
evaluating the crosstalk between different epigenetic mechanisms are largely
missing. In summary, despite that there is a clear evidence of epigenetic
impairment in AITD, further research is required for a better understanding of
the epigenetic networks involved in disease pathogenesis, thereby opening the way
for potential diagnostic and prognostic tools, as well as for epigenetic
interventions in the patients.
PMID- 28706508
TI - Assessment of the Potential Role of Streptomyces in Cave Moonmilk Formation.
AB - Moonmilk is a karstic speleothem mainly composed of fine calcium carbonate
crystals (CaCO3) with different textures ranging from pasty to hard, in which the
contribution of biotic rock-building processes is presumed to involve indigenous
microorganisms. The real microbial input in the genesis of moonmilk is difficult
to assess leading to controversial hypotheses explaining the origins and the
mechanisms (biotic vs. abiotic) involved. In this work, we undertook a
comprehensive approach in order to assess the potential role of filamentous
bacteria, particularly a collection of moonmilk-originating Streptomyces, in the
genesis of this speleothem. Scanning electron microscopy (SEM) confirmed that
indigenous filamentous bacteria could indeed participate in moonmilk development
by serving as nucleation sites for CaCO3 deposition. The metabolic activities
involved in CaCO3 transformation were furthermore assessed in vitro among the
collection of moonmilk Streptomyces, which revealed that peptides/amino acids
ammonification, and to a lesser extend ureolysis, could be privileged metabolic
pathways participating in carbonate precipitation by increasing the pH of the
bacterial environment. Additionally, in silico search for the genes involved in
biomineralization processes including ureolysis, dissimilatory nitrate reduction
to ammonia, active calcium ion transport, and reversible hydration of CO2 allowed
to identify genetic predispositions for carbonate precipitation in Streptomyces.
Finally, their biomineralization abilities were confirmed by environmental SEM,
which allowed to visualize the formation of abundant mineral deposits under
laboratory conditions. Overall, our study provides novel evidences that
filamentous Actinobacteria could be key protagonists in the genesis of moonmilk
through a wide spectrum of biomineralization processes.
PMID- 28706509
TI - Comparing the Ecological Stoichiometry in Green and Brown Food Webs - A Review
and Meta-analysis of Freshwater Food Webs.
AB - The framework of ecological stoichiometry was developed primarily within the
context of "green" autotroph-based food webs. While stoichiometric principles
also apply in "brown" detritus-based systems, these systems have been
historically understudied and differ from green ones in several important aspects
including carbon (C) quality and the nutrient [nitrogen (N) and phosphorus (P)]
contents of food resources for consumers. In this paper, we review work over the
last decade that has advanced the application of ecological stoichiometry from
green to brown food webs, focusing on freshwater ecosystems. We first review
three focal areas where green and brown food webs differ: (1) bottom-up controls
by light and nutrient availability, (2) stoichiometric constraints on consumer
growth and nutritional regulation, and (3) patterns in consumer-driven nutrient
dynamics. Our review highlights the need for further study of how light and
nutrient availability affect autotroph-heterotroph interactions on detritus and
the subsequent effects on consumer feeding and growth. To complement this
conceptual review, we formally quantified differences in stoichiometric
principles between green and brown food webs using a meta-analysis across feeding
studies of freshwater benthic invertebrates. From 257 datasets collated across 46
publications and several unpublished studies, we compared effect sizes (Pearson's
r) of resource N:C and P:C on growth, consumption, excretion, and egestion
between herbivorous and detritivorous consumers. The meta-analysis revealed that
both herbivore and detritivore growth are limited by resource N:C and P:C
contents, but effect sizes only among detritivores were significantly above zero.
Consumption effect sizes were negative among herbivores but positive for
detritivores in the case of both N:C and P:C, indicating distinct compensatory
feeding responses across resource stoichiometry gradients. Herbivore P excretion
rates responded significantly positively to resource P:C, whereas detritivore N
and P excretion did not respond; detritivore N and P egestion responded
positively to resource N:C and P:C, respectively. Our meta-analysis highlights
resource N and P contents as broadly limiting in brown and green benthic food
webs, but indicates contrasting mechanisms of limitation owing to differing
consumer regulation. We suggest that green and brown food webs share fundamental
stoichiometric principles, while identifying specific differences toward applying
ecological stoichiometry across ecosystems.
PMID- 28706510
TI - Natural Killer Cell Functions during the Innate Immune Response to Pathogenic
Streptococci.
AB - Dendritic cells (DCs) and NK cells play a crucial role in the first phase of host
defense against infections. Group B Streptococcus (GBS) and Streptococcus suis
are encapsulated streptococci causing severe systemic inflammation, leading to
septicemia and meningitis. Yet, the involvement of NK cells in the innate immune
response to encapsulated bacterial infection is poorly characterized. Here, it
was observed that these two streptococcal species rapidly induce the release of
IFN-gamma and that NK cells are the major cell type responsible for this
production during the acute phase of the infection. Albeit S. suis capacity to
activate NK cells was lower than that of GBS, these cells partially contribute to
S. suis systemic infection; mainly through amplification of the inflammatory
loop. In contrast, such a role was not observed during GBS systemic infection.
IFN-gamma release by NK cells required the presence of DCs, which in turn had a
synergistic effect on DC cytokine production. These responses were mainly
mediated by direct DC-NK cell contact and partially dependent on soluble factors.
Though IL-12 and LFA-1 were shown to be critical in S. suis-mediated activation
of the DC-NK cell crosstalk, different or redundant molecular pathways modulate
DC-NK interactions during GBS infection. The bacterial capsular polysaccharides
also differently modulated NK cell activation. Together, these results
demonstrated a role of NK cells in the innate immune response against
encapsulated streptococcal infections; yet the molecular pathways governing NK
activation seem to differ upon the pathogen and should not be generalized when
studying bacterial infections.
PMID- 28706511
TI - Exoproteome Analysis of the Seaweed Pathogen Nautella italica R11 Reveals
Temperature-Dependent Regulation of RTX-Like Proteins.
AB - Climate fluctuations have been linked to an increased prevalence of disease in
seaweeds, including the red alga Delisea pulchra, which is susceptible to a
bleaching disease caused by the bacterium Nautella italica R11 under elevated
seawater temperatures. To further investigate the role of temperature in the
induction of disease by N. italica R11, we assessed the effect of temperature on
the expression of the extracellular proteome (exoproteome) in this bacterium.
Label-free quantitative mass spectrometry was used to identify 207 proteins
secreted into supernatant fraction, which is equivalent to 5% of the protein
coding genes in the N. italica R11 genome. Comparative analysis demonstrated that
expression of over 30% of the N. italica R11 exoproteome is affected by
temperature. The temperature-dependent proteins include traits that could
facilitate the ATP-dependent transport of amino acid and carbohydrate, as well as
several uncharacterized proteins. Further, potential virulence determinants,
including two RTX-like proteins, exhibited significantly higher expression in the
exoproteome at the disease inducing temperature of 24 degrees C relative to non
inducing temperature (16 degrees C). This is the first study to demonstrate that
temperature has an influence exoproteome expression in a macroalgal pathogen. The
results have revealed several temperature regulated candidate virulence factors
that may have a role in macroalgal colonization and invasion at elevated sea
surface temperatures, including novel RTX-like proteins.
PMID- 28706512
TI - Comparative Genomics Reveals High Genomic Diversity in the Genus Photobacterium.
AB - Vibrionaceae is a large marine bacterial family, which can constitute up to 50%
of the prokaryotic population in marine waters. Photobacterium is the second
largest genus in the family and we used comparative genomics on 35 strains
representing 16 of the 28 species described so far, to understand the genomic
diversity present in the Photobacterium genus. Such understanding is important
for ecophysiology studies of the genus. We used whole genome sequences to
evaluate phylogenetic relationships using several analyses (16S rRNA, MLSA, fur,
amino-acid usage, ANI), which allowed us to identify two misidentified strains.
Genome analyses also revealed occurrence of higher and lower GC content clades,
correlating with phylogenetic clusters. Pan- and core-genome analysis revealed
the conservation of 25% of the genome throughout the genus, with a large and open
pan-genome. The major source of genomic diversity could be traced to the smaller
chromosome and plasmids. Several of the physiological traits studied in the genus
did not correlate with phylogenetic data. Since horizontal gene transfer (HGT) is
often suggested as a source of genetic diversity and a potential driver of
genomic evolution in bacterial species, we looked into evidence of such in
Photobacterium genomes. Genomic islands were the source of genomic differences
between strains of the same species. Also, we found transposase genes and CRISPR
arrays that suggest multiple encounters with foreign DNA. Presence of genomic
exchange traits was widespread and abundant in the genus, suggesting a role in
genomic evolution. The high genetic variability and indications of genetic
exchange make it difficult to elucidate genome evolutionary paths and raise the
awareness of the roles of foreign DNA in the genomic evolution of environmental
organisms.
PMID- 28706514
TI - Evaluation of the Bruker Biotyper Matrix-Assisted Laser Desorption/Ionization
Time-of-Flight Mass Spectrometry System for Identification of Aspergillus Species
Directly from Growth on Solid Agar Media.
AB - We evaluated the accuracy of the Bruker Biotyper matrix-assisted laser
desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) system at
identifying clinical isolates of Aspergillus species that were grown on agar
media. A total of 381 non-duplicate Aspergillus isolates representing 21
different Aspergillus species identified by molecular analysis were included in
this study. The Bruker Biotyper MALDI-TOF MS system was able to identify 30.2%
(115/381) of the isolates to the species level (score values of >=2.000) and
49.3% to the genus level (score values of 1.700-1.999). When the identification
cutoff value was lowered from >=2.000 to >=1.700, the species-level
identification rate increased to 79.5% with a slight rise of false identification
from 2.6 to 5.0%. From another aspect, a correct species-level identification
rate of 89% could be reached by the Bruker Biotyper MALDI-TOF MS system
regardless of the score values obtained. The Bruker Biotyper MALDI-TOF MS system
had a moderate performance in identification of Aspergillus directly inoculated
on solid agar media. Continued expansion of the Bruker Biotyper MALDI-TOF MS
database and adoption of alternative cutoff values for interpretation are
required to improve the performance of the system for identifying highly diverse
species of clinically encountered Aspergillus isolates.
PMID- 28706513
TI - Bacteriocin-Antimicrobial Synergy: A Medical and Food Perspective.
AB - The continuing emergence of multi-drug resistant pathogens has sparked an
interest in seeking alternative therapeutic options. Antimicrobial combinatorial
therapy is one such avenue. A number of studies have been conducted, involving
combinations of bacteriocins with other antimicrobials, to circumvent the
development of antimicrobial resistance and/or increase antimicrobial potency.
Such bacteriocin-antimicrobial combinations could have tremendous value, in terms
of reducing the likelihood of resistance development due to the involvement of
two distinct mechanisms of antimicrobial action. Furthermore, antimicrobial
synergistic interactions may also have potential financial implications in terms
of decreasing the costs of treatment by reducing the concentration of an
expensive antimicrobial and utilizing it in combination with an inexpensive one.
In addition, combinatorial therapies with bacteriocins can broaden antimicrobial
spectra and/or result in a reduction in the concentration of an antibiotic
required for effective treatments to the extent that potentially toxic or adverse
side effects can be reduced or eliminated. Here, we review studies in which
bacteriocins were found to be effective in combination with other antimicrobials,
with a view to targeting clinical and/or food-borne pathogens. Furthermore, we
discuss some of the bottlenecks which are currently hindering the development of
bacteriocins as viable therapeutic options, as well as addressing the need to
exercise caution when attempting to predict clinical outcomes of bacteriocin
antimicrobial combinations.
PMID- 28706515
TI - More Pathogenicity or Just More Pathogens?-On the Interpretation Problem of
Multiple Pathogen Detections with Diagnostic Multiplex Assays.
AB - Modern molecular diagnostic approaches in the diagnostic microbiological
laboratory like real-time quantitative polymerase chain reaction (qPCR) have led
to a considerable increase of diagnostic sensitivity. They usually outperform the
diagnostic sensitivity of culture-based approaches. Culture-based diagnostics
were found to be insufficiently sensitive for the assessment of the composition
of biofilms in chronic wounds and poorly standardized for screenings for enteric
colonization with multi-drug resistant bacteria. However, the increased
sensitivity of qPCR causes interpretative challenges regarding the attribution of
etiological relevance to individual pathogen species in case of multiple
detections of facultative pathogenic microorganisms in primarily non-sterile
sample materials. This is particularly the case in high-endemicity settings,
where continuous exposition to respective microorganisms leads to immunological
adaptation and semi-resistance while considerable disease would result in case of
exposition of a non-adapted population. While biofilms in chronic wounds show
higher pathogenic potential in case of multi-species composition, detection of
multiple pathogens in respiratory samples is much more difficult to interpret and
asymptomatic enteric colonization with facultative pathogenic microorganisms is
frequently observed in high endemicity settings. For respiratory samples and
stool samples, cycle-threshold-value-based semi-quantitative interpretation of
qPCR results has been suggested. Etiological relevance is assumed if cycle
threshold values are low, suggesting high pathogen loads. Although the procedure
is challenged by lacking standardization and methodical issues, first evaluations
have led to promising results. Future studies should aim at generally acceptable
quantitative cut-off values to allow discrimination of asymptomatic colonization
from clinically relevant infection.
PMID- 28706516
TI - Applying Precision Medicine and Immunotherapy Advances from Oncology to Host
Directed Therapies for Infectious Diseases.
AB - To meet the challenges of increasing antimicrobial resistance, the infectious
disease community needs innovative therapeutics. Precision medicine and
immunotherapies are transforming cancer therapeutics by targeting the regulatory
signaling pathways that are involved not only in malignancies but also in the
metabolic and immunologic function of the tumor microenvironment. Infectious
diseases target many of the same regulatory pathways as they modulate host
metabolic functions for their own nutritional requirements and to impede host
immunity. These similarities and the advances made in precision medicine and
immuno-oncology that are relevant for the current development of host-directed
therapies (HDTs) to treat infectious diseases are discussed. To harness this
potential, improvements in drug screening methods and development of assays that
utilize the research tools including high throughput multiplexes already
developed by oncology are essential. A multidisciplinary approach that brings
together immunologists, infectious disease specialists, and oncologists will be
necessary to fully develop the potential of HDTs.
PMID- 28706517
TI - Negative Regulation of Hepatic Inflammation by the Soluble Resistance-Related
Calcium-Binding Protein via Signal Transducer and Activator of Transcription 3.
AB - Host immune response is tightly controlled by negative regulators to avoid
excessive immune reactions for homeostasis. Some pathogens may take advantage of
host negative regulating system to evade host defense. Our previous report showed
that foot-and-mouth disease virus (FMDV) VP1 inhibited TNF-alpha- and SeV-induced
type I interferon response via interaction with cellular protein soluble
resistance-related calcium-binding protein (sorcin). Conversely, TNF-alpha- or
SeV-induced type I interferon response increased when sorcin knocked down,
leading to inhibition of vesicular stomatitis virus replication. However, the
exact role of sorcin in regulation of the immune response is still not clear.
Here, we show that mice deficient of sorcin (sorcin-/-) display enhanced ConA
induced hepatitis. Importantly, splenocytes from sorcin-/- mice produced more IL
2, IL-4, IL-17, and IFN-gamma than that of littermate controls (sorcin+/+) in
response to anti-CD3/28 stimulation. Furthermore, our data indicate that sorcin
interacts with signal transducer and activator of transcription 3 (STAT3) and
enhances its phosphorylation and that STAT3 acts as an immediate downstream
molecule of sorcin in the negative regulation of NF-kappaB signaling. Thus,
sorcin, in association with STAT3, negatively regulates hepatic inflammation.
PMID- 28706518
TI - Immunization with Toxoplasma gondii GRA17 Deletion Mutant Induces Partial
Protection and Survival in Challenged Mice.
AB - Toxoplasmosis remains a world-threatening disease largely because of the lack of
a fully effective vaccine. Here, we created a DeltaGRA17 mutant by disrupting the
virulence factor GRA17 using CRISPR-Cas9 method. Then, we tested whether
DeltaGRA17 tachyzoites can be used as a live-attenuated vaccine against acute,
chronic, and congenital Toxoplasma gondii infection in mice. Immune response
evoked by DeltaGRA17 immunization suggested a sequential Th1 and Th2 T cell
response, indicated by high levels of Th1 and a mixed Th1/Th2 cytokines at 28 and
70 days after immunization, respectively. DeltaGRA17-mediated immunity fully
protected mice against lethal infection with wild-type (wt) RH strain,
heterologous challenge with PYS, and TgC7 strains of the Chinese ToxoDB#9
genotype, and T. gondii Pru strain. Although parasite cysts were detected in 8
out of 10 immunized mice, cyst burden in the brain was significantly reduced (P <
0.05) in immunized mice (53 +/- 15 cysts/brain) compared to non-immunized mice
(4,296 +/- 687 cysts/brain). In respect to congenital infection, the litter size,
survival rate, and body weight (BW) of pups born to DeltaGRA17-immunized dams
were not different compared to pups born to naive control dams (P = 0.24).
However, a marked reduction in the litter size (P < 0.001), survival rate, and BW
(P < 0.01) of pups born to non-immunized and infected dams was detected. Also,
immunized dams infected with type II Pru strain had significantly (P < 0.001)
less cyst burden in the brain compared with non-immunized and infected dams.
These findings show that immunization with DeltaGRA17 strain evokes cell-mediated
and neutralizing antibody responses and confers some degree of protection against
challenge with homologous and heterologous virulent T. gondii strains.
PMID- 28706519
TI - Estrogens Promote the Production of Natural Neutralizing Antibodies in Fish
through G Protein-Coupled Estrogen Receptor 1.
AB - Natural antibodies play crucial roles in pathogen elimination, B-cell survival
and homeostasis, and inflammatory and autoimmune diseases. Although estrogens are
able to regulate both innate and adaptive immune responses, their role in the
production of natural antibodies is unknown. Here, we show that the dietary
intake of the synthetic estradiol analog, 17alpha-ethinylestradiol (EE2), one of
the most potent pharmaceutical estrogens and intensively used in human
therapeutics as a component of most oral contraceptives, regulates the abundance
and proliferation of T and IgM+ B lymphocytes in the teleost fish gilthead
seabream (Sparus aurata L.). Furthermore, for the first time in vertebrates, it
is shown that estrogen signaling through G protein-coupled estrogen receptor 1
(GPER1) induces the production of polyreactive natural antibodies, which are able
to crossreact with unrelated antigens and commensal and pathogenic bacteria. In
addition, the serum from fish treated with EE2 or the GPER1 agonist G1 shows
higher complement-dependent bactericidal activity than that from non-treated
specimens. These results demonstrate that estrogens and GPER1 are the key
regulators of natural antibody production and pathogen clearance in fish, paving
the way for future studies in other vertebrate classes.
PMID- 28706520
TI - Hypothermia Promotes Interleukin-22 Expression and Fine-Tunes Its Biological
Activity.
AB - Disturbed homeostasis as a result of tissue stress can provoke leukocyte
responses enabling recovery. Since mild hypothermia displays specific clinically
relevant tissue-protective properties and interleukin (IL)-22 promotes healing at
host/environment interfaces, effects of lowered ambient temperature on IL-22 were
studied. We demonstrate that a 5-h exposure of endotoxemic mice to 4 degrees C
reduces body temperature by 5.0 degrees and enhances splenic and colonic il22
gene expression. In contrast, tumor necrosis factor-alpha and IL-17A were not
increased. In vivo data on IL-22 were corroborated using murine splenocytes and
human peripheral blood mononuclear cells (PBMC) cultured upon 33 degrees C and
polyclonal T cell activation. Upregulation by mild hypothermia of largely T-cell
derived IL-22 in PBMC required monocytes and associated with enhanced nuclear T
cell nuclear factor of activated T cells (NFAT)-c2. Notably, NFAT antagonism by
cyclosporin A or FK506 impaired IL-22 upregulation at normothermia and entirely
prevented its enhanced expression upon hypothermic culture conditions. Data
suggest that intact NFAT signaling is required for efficient IL-22 induction upon
normothermic and hypothermic conditions. Hypothermia furthermore boosted early
signal transducer and activator of transcription 3 activation by IL-22 and shaped
downstream gene expression in epithelial-like cells. Altogether, data indicate
that hypothermia supports and fine-tunes IL-22 production/action, which may
contribute to regulatory properties of low ambient temperature.
PMID- 28706521
TI - Evolution and Function of Thioester-Containing Proteins and the Complement System
in the Innate Immune Response.
AB - The innate immune response is evolutionary conserved among organisms. The
complement system forms an important and efficient immune defense mechanism. It
consists of plasma proteins that participate in microbial detection, which
ultimately results in the production of various molecules with antimicrobial
activity. Thioester-containing proteins (TEPs) are a superfamily of secreted
effector proteins. In vertebrates, certain TEPs act in the innate immune response
by promoting recruitment of immune cells, phagocytosis, and direct lysis of
microbial invaders. Insects are excellent models for dissecting the molecular
basis of innate immune recognition and response to a wide range of microbial
infections. Impressive progress in recent years has generated crucial information
on the role of TEPs in the antibacterial and antiparasite response of the
tractable model insect Drosophila melanogaster and the mosquito malaria vector
Anopheles gambiae. This knowledge is critical for better understanding the
evolution of TEPs and their involvement in the regulation of the host innate
immune system.
PMID- 28706522
TI - Expressed Centromere Specific Histone 3 (CENH3) Variants in Cultivated Triploid
and Wild Diploid Bananas (Musa spp.).
AB - Centromeres are specified by a centromere specific histone 3 (CENH3) protein,
which exists in a complex environment, interacting with conserved proteins and
rapidly evolving satellite DNA sequences. The interactions may become more
challenging if multiple CENH3 versions are introduced into the zygote as this can
affect post-zygotic mitosis and ultimately sexual reproduction. Here, we
characterize CENH3 variant transcripts expressed in cultivated triploid and wild
diploid progenitor bananas. We describe both splice- and allelic-[Single
Nucleotide Polymorphisms (SNP)] variants and their effects on the predicted
secondary structures of protein. Expressed CENH3 transcripts from six banana
genotypes were characterized and clustered into three groups (MusaCENH-1A,
MusaCENH-1B, and MusaCENH-2) based on similarity. The CENH3 groups differed with
SNPs as well as presence of indels resulting from retained and/or skipped exons.
The CENH3 transcripts from different banana genotypes were spliced in either 7/6,
5/4 or 6/5 exons/introns. The 7/6 and the 5/4 exon/intron structures were found
in both diploids and triploids, however, 7/6 was most predominant. The 6/5
exon/introns structure was a result of failure of the 7/6 to splice correctly.
The various transcripts obtained were predicted to encode highly variable N
terminal tails and a relatively conserved C-terminal histone fold domain (HFD).
The SNPs were predicted in some cases to affect the secondary structure of
protein by lengthening or shorting the affected domains. Sequencing of banana
CENH3 transcripts predicts SNP variations that affect amino acid sequences and
alternatively spliced transcripts. Most of these changes affect the N-terminal
tail of CENH3.
PMID- 28706523
TI - Identification of Optimal Reference Genes for Normalization of qPCR Analysis
during Pepper Fruit Development.
AB - Due to its high sensitivity and reproducibility, quantitative real-time PCR
(qPCR) is practiced as a useful research tool for targeted gene expression
analysis. For qPCR operations, the normalization with suitable reference genes
(RGs) is a crucial step that eventually determines the reliability of the
obtained results. Although pepper is considered an ideal model plant for the
study of non-climacteric fruit development, at present no specific RG have been
developed or validated for the qPCR analyses of pepper fruit. Therefore, this
study aimed to identify stably expressed genes for their potential use as RGs in
pepper fruit studies. Initially, a total of 35 putative RGs were selected by
mining the pepper transcriptome data sets derived from the PGP (Pepper Genome
Platform) and PGD (Pepper Genome Database). Their expression stabilities were
further measured in a set of pepper (Capsicum annuum L. var. 007e) fruit samples,
which represented four different fruit developmental stages (IM: Immature; MG:
Mature green; B: Break; MR: Mature red) using the qPCR analysis. Then, based on
the qPCR results, three different statistical algorithms, namely geNorm,
Normfinder, and boxplot, were chosen to evaluate the expression stabilities of
these putative RGs. It should be noted that nine genes were proven to be
qualified as RGs during pepper fruit development, namely CaREV05 (CA00g79660);
CaREV08 (CA06g02180); CaREV09 (CA06g05650); CaREV16 (Capana12g002666); CaREV21
(Capana10g001439); CaREV23 (Capana05g000680); CaREV26 (Capana01g002973); CaREV27
(Capana11g000123); CaREV31 (Capana04g002411); and CaREV33 (Capana08g001826).
Further analysis based on geNorm suggested that the application of the two most
stably expressed genes (CaREV05 and CaREV08) would provide optimal transcript
normalization in the qPCR experiments. Therefore, a new and comprehensive
strategy for the identification of optimal RGs was developed. This strategy
allowed for the effective normalization of the qPCR analysis of the pepper fruit
development at the whole pepper genome level. This study not only explored the
optimal RGs specific for studying pepper fruit development, but also introduced a
referable strategy of RG mining which could potentially be implicated in other
plant species.
PMID- 28706524
TI - Evaluation of Wild Lentil Species as Genetic Resources to Improve Drought
Tolerance in Cultivated Lentil.
AB - Increasingly unpredictable annual rainfall amounts and distribution patterns have
far reaching implications for pulse crop biology. Seedling and whole plant
survival will be affected given that water is a key factor in plant
photosynthesis and also influences the evolving disease spectrum that affects
crops. The wild relatives of cultivated lentil are native to drought prone areas,
making them good candidates for the evaluation of drought tolerance traits. We
evaluated root and shoot traits of genotypes of cultivated lentil and five wild
species grown under two water deficit regimes as well as fully watered conditions
over a 13 week period indoors. Plants were grown in sectioned polyvinyl chloride
(PVC) tubes containing field soil from the A, B, and C horizons. We found that
root distribution into different soil horizons varied among wild lentil
genotypes. Secondly, wild lentil genotypes employed diverse strategies such as
delayed flowering, reduced transpiration rates, reduced plant height, and deep
root systems to either escape, evade or tolerate drought conditions. In some
cases, more than one drought strategy was observed within the same genotype.
Sequence based classification of wild and cultivated genotypes did not explain
patterns of drought response. The environmental conditions at their centers of
origin may explain the patterns of drought strategies observed in wild lentils.
The production of numerous small seeds by wild lentil genotypes may have
implications for yield improvement in lentil breeding programs.
PMID- 28706525
TI - Functional Marker Assisted Improvement of Stable Cytoplasmic Male Sterile Lines
of Rice for Bacterial Blight Resistance.
AB - Bacterial blight (BB), caused by Xanthomonas oryzae pv.oryzae is one among the
major diseases in rice, which in severe condition cause losses up to 60% in total
yield. Marker assisted pyramiding of three broad spectrum BB resistance genes
(xa5, xa13, and Xa21) in prominent rice varieties is the most economical and
effective strategy for the management of the BB disease. We report here the
pyramiding of three genes (xa5, xa13, and Xa21) in maintainer lines (CO 2B, CO
23B, and CO 24B) of three promising wild abortive cytoplasmic male sterile lines
(CO 2A, CO 23A, and CO 24A) through functional markers assisted back cross
breeding. IRBB60 with xa5, xa13, and Xa21 genes is used as a donor parent. BC2F1
and BC2F2 generations from a cross of CO 2B, CO 23B, and CO 24B with IRBB60 were
evaluated for bacterial blight and non-fertility restoration. In BC2F1, plants
with all three resistance genes (xa5, xa13, and Xa21) and high parent genome
recovery was identified. In BC2F2, plants with all resistance genes and without
fertility restorer (Rf3 and Rf4) were selected. Based on agronomic traits, BB
resistance and maintenance of sterility, two plants each in CO 2B * IRBB60, CO
24B * IRBB60 and one plant in CO 23B * IRBB60 combinations were identified. The
identified lines were crossed with respective male sterile lines for conversion
of improved B line into CMS line through back-crossing, in addition to selfing.
The plants with high recurrent genome and phenotypically similar to parental
lines and sterile are being used for the hybrid rice development program.
Currently, using these lines (improved CMS line), test crosses were made to
develop new rice hybrids. Hybrids combinations viz., CO 23A * AD08009R and CO 24A
* IET20898R were found to be stable at different locations with high yield. The R
line used in this study has been introgressed with xa5, xa13, and Xa21 genes in a
separate breeding program. These new hybrids with resistance against bacterial
blight will increase the crop production at BB environment.
PMID- 28706526
TI - Molecular Breeding for Ascochyta Blight Resistance in Lentil: Current Progress
and Future Directions.
AB - Lentil (Lens culinaris Medik.) is a diploid (2n = 2x = 14), self-pollinating,
cool-season, grain legume that is cultivated worldwide and is highly valuable due
to its high protein content. However, lentil production is constrained by many
factors including biotic stresses, majority of which are fungal diseases such as
ascochyta blight (AB), fusarium wilt, rust, stemphylium blight, anthracnose, and
botrytis gray mold. Among various diseases, AB is a major -problem in many lentil
producing countries and can significantly reduce crop production. Breeding for AB
resistance has been a priority for breeding programs across the globe and
consequently, a number of resistance sources have been identified and extensively
exploited. In order to increase the efficiency of combining genes from different
genetic backgrounds, molecular genetic tools can be integrated with conventional
breeding methods. A range of genetic linkage maps have been generated based on
DNA-based markers, and quantitative trait loci (QTLs) for AB resistance have been
identified. Molecular markers linked to these QTLs may potentially be used for
efficient pyramiding of the AB disease resistance genes. Significant genomic
resources have been established to identify and characterize resistance genes,
including an integrated genetic map, expressed sequence tag libraries, gene based
markers, and draft genome sequences. These resources are already being utilized
for lentil crop improvement, to more effectively select for disease resistance,
as a case study of the Australian breeding program will show. The combination of
genomic resources, effective molecular genetic tools and high resolution
phenotyping tools will improve the efficiency of selection for ascochyta blight
resistance and accelerate varietal development of global lentil breeding
programs.
PMID- 28706527
TI - Localization of Sphingolipid Enriched Plasma Membrane Regions and Long-Chain Base
Composition during Mature-Fruit Abscission in Olive.
AB - Sphingolipids, found in membranes of eukaryotic cells, have been demonstrated to
carry out functions in various processes in plant cells. However, the roles of
these lipids in fruit abscission remain to be determined in plants. Biochemical
and fluorescence microscopy imaging approach has been adopted to investigate the
accumulation and distribution of sphingolipids during mature-fruit abscission in
olive (Olea europaea L. cv. Picual). Here, a lipid-content analysis in live
protoplasts of the olive abscission zone (AZ) was made with fluorescent dyes and
lipid analogs, particularly plasma membrane sphingolipid-enriched domains, and
their dynamics were investigated in relation to the timing of mature-fruit
abscission. In olive AZ cells, the measured proportion of both polar lipids and
sphingolipids increased as well as endocytosis was stimulated during mature-fruit
abscission. Likewise, mature-fruit abscission resulted in quantitative and
qualitative changes in sphingolipid long-chain bases (LCBs) in the olive AZ. The
total LCB increase was due essentially to the increase of t18:1(8E) LCBs,
suggesting that C-4 hydroxylation and Delta8 desaturation with a preference for
(E)-isomer formation were quantitatively the most important sphingolipids in
olive AZ during abscission. However, our results also showed a specific
association between the dihydroxylated LCB sphinganine (d18:0) and the mature
fruit abscission. These results indicate a clear correlation between the
sphingolipid composition and mature-fruit abscission. Moreover, measurements of
endogenous sterol levels in the olive AZ revealed that it accumulated sitosterol
and campesterol with a concomitant decrease in cycloartenol during abscission. In
addition, underlying the distinct sterol composition of AZ during abscission,
genes for key biosynthetic enzymes for sterol synthesis, for obtusifoliol 14alpha
demethylase (CYP51) and C-24 sterol methyltransferase2 (SMT2), were up-regulated
during mature-fruit abscission, in parallel to the increase in sitosterol
content. The differences found in AZ lipid content and the relationships
established between LCB and sterol composition, offer new insights about
sphingolipids and sterols in abscission.
PMID- 28706528
TI - Molecular Mechanisms behind the Physiological Resistance to Intense Transient
Warming in an Iconic Marine Plant.
AB - The endemic Mediterranean seagrass Posidonia oceanica is highly threatened by the
increased frequency and intensity of heatwaves. Meadows of the species offer a
unique opportunity to unravel mechanisms marine plants activate to cope transient
warming, since their wide depth distribution impose divergent heat-tolerance.
Understanding these mechanisms is imperative for their conservation. Shallow and
deep genotypes within the same population were exposed to a simulated heatwave in
mesocosms, to analyze their transcriptomic and photo-physiological responses
during and after the exposure. Shallow plants, living in a more unstable thermal
environment, optimized phenotype variation in response to warming. These plants
showed a pre-adaptation of genes in anticipation of stress. Shallow plants also
showed a stronger activation of heat-responsive genes and the exclusive
activation of genes involved in epigenetic mechanisms and in molecular mechanisms
that are behind their higher photosynthetic stability and respiratory
acclimation. Deep plants experienced higher heat-induced damage and activated
metabolic processes for obtaining extra energy from sugars and amino acids,
likely to support the higher protein turnover induced by heat. In this study we
identify transcriptomic mechanisms that may facilitate persistence of seagrasses
to anomalous warming events and we discovered that P. oceanica plants from above
and below the mean depth of the summer thermocline have differential resilience
to heat.
PMID- 28706529
TI - Bacillus licheniformis SA03 Confers Increased Saline-Alkaline Tolerance in
Chrysanthemum Plants by Induction of Abscisic Acid Accumulation.
AB - Soil saline-alkalization is a major abiotic stress that leads to low iron (Fe)
availability and high toxicity of sodium ions (Na+) for plants. It has recently
been shown that plant growth promoting rhizobacteria (PGPR) can enhance the
ability of plants to tolerate multiple abiotic stresses such as drought,
salinity, and nutrient deficiency. However, the possible involvement of PGPR in
improving saline-alkaline tolerance of plants and the underlying mechanisms
remain largely unknown. In this study, we investigated the effects of Bacillus
licheniformis (strain SA03) on the growth of Chrysanthemum plants under saline
alkaline conditions. Our results revealed that inoculation with SA03 alleviated
saline-alkaline stress in plants with increased survival rates, photosynthesis
and biomass. The inoculated plants accumulated more Fe and lower Na+
concentrations under saline-alkaline stress compared with the non-inoculated
plants. RNA-Sequencing analyses further revealed that SA03 significantly
activated abiotic stress- and Fe acquisition-related pathways in the stress
treated plants. However, SA03 failed to increase saline-alkaline tolerance in
plants when cellular abscisic acid (ABA) and nitric oxide (NO) synthesis were
inhibited by treatment with fluridone (FLU) and 2-(4-carboxyphenyl)-4,4,5,5
tetramethylimidazoline-1-oxyl-3-oxide (c-PTIO), respectively. Importantly, we
also found that NO acted downstream of SA03-induced ABA to activate a series of
adaptive responses in host plants under saline-alkaline stress. These findings
demonstrated the potential roles of B. licheniformis SA03 in enhancing saline
alkaline tolerance of plants and highlighted the intricate integration of
microbial signaling in regulating cellular Fe and Na+ accumulation.
PMID- 28706530
TI - FtsH2-Dependent Proteolysis of EXECUTER1 Is Essential in Mediating Singlet Oxygen
Triggered Retrograde Signaling in Arabidopsis thaliana.
AB - Photosystem II reaction center (PSII RC) and light-harvesting complex inevitably
generate highly reactive singlet oxygen (1O2) that can impose photo-oxidative
damage, especially when the rate of generation exceeds the rate of
detoxification. Besides being toxic, 1O2 has also been ascribed to trigger
retrograde signaling, which leads to nuclear gene expression changes. Two
distinctive molecular components appear to regulate 1O2 signaling: a volatile
signaling molecule beta-cyclocitral (beta-CC) generated upon oxidation of beta
carotene by 1O2 in PSII RC assembled in grana core, and a thylakoid membrane
bound FtsH2 metalloprotease that promotes 1O2-triggered signaling through the
proteolysis of EXECUTER1 (EX1) proteins associated with PSII in grana margin. The
role of FtsH2 protease in 1O2 signaling was established recently in the
conditional fluorescent (flu) mutant of Arabidopsis thaliana that generates 1O2
upon dark-to-light shift. The flu mutant lacking functional FtsH2 significantly
impairs 1O2-triggered and EX1-mediated cell death. In the present study, the role
of FtsH2 in the induction of 1O2 signaling was further clarified by analyzing the
FtsH2-dependent nuclear gene expression changes in the flu mutant. Genome-wide
transcriptome analysis showed that the inactivation of FtsH2 repressed the
majority (85%) of the EX1-dependent 1O2-responsive genes (SORGs), providing
direct connection between FtsH2-mediated EX1 degradation and 1O2-triggered gene
expression changes. Furthermore, the overlap between beta-CC-induced genes and
EX1-FtsH2-dependent genes was very limited, further supporting the coexistence of
two distinctive 1O2 signaling pathways.
PMID- 28706531
TI - Crop Production under Drought and Heat Stress: Plant Responses and Management
Options.
AB - Abiotic stresses are one of the major constraints to crop production and food
security worldwide. The situation has aggravated due to the drastic and rapid
changes in global climate. Heat and drought are undoubtedly the two most
important stresses having huge impact on growth and productivity of the crops. It
is very important to understand the physiological, biochemical, and ecological
interventions related to these stresses for better management. A wide range of
plant responses to these stresses could be generalized into morphological,
physiological, and biochemical responses. Interestingly, this review provides a
detailed account of plant responses to heat and drought stresses with special
focus on highlighting the commonalities and differences. Crop growth and yields
are negatively affected by sub-optimal water supply and abnormal temperatures due
to physical damages, physiological disruptions, and biochemical changes. Both
these stresses have multi-lateral impacts and therefore, complex in mechanistic
action. A better understanding of plant responses to these stresses has pragmatic
implication for remedies and management. A comprehensive account of conventional
as well as modern approaches to deal with heat and drought stresses have also
been presented here. A side-by-side critical discussion on salient responses and
management strategies for these two important abiotic stresses provides a unique
insight into the phenomena. A holistic approach taking into account the different
management options to deal with heat and drought stress simultaneously could be a
win-win approach in future.
PMID- 28706532
TI - Identification of Single-Nucleotide Polymorphic Loci Associated with Biomass
Yield under Water Deficit in Alfalfa (Medicago sativa L.) Using Genome-Wide
Sequencing and Association Mapping.
AB - Alfalfa is a worldwide grown forage crop and is important due to its high biomass
production and nutritional value. However, the production of alfalfa is
challenged by adverse environmental factors such as drought and other stresses.
Developing drought resistance alfalfa is an important breeding target for
enhancing alfalfa productivity in arid and semi-arid regions. In the present
study, we used genotyping-by-sequencing and genome-wide association to identify
marker loci associated with biomass yield under drought in the field in a panel
of diverse germplasm of alfalfa. A total of 28 markers at 22 genetic loci were
associated with yield under water deficit, whereas only four markers associated
with the same trait under well-watered condition. Comparisons of marker-trait
associations between water deficit and well-watered conditions showed non
similarity except one. Most of the markers were identical across harvest periods
within the treatment, although different levels of significance were found among
the three harvests. The loci associated with biomass yield under water deficit
located throughout all chromosomes in the alfalfa genome agreed with previous
reports. Our results suggest that biomass yield under drought is a complex
quantitative trait with polygenic inheritance and may involve a different
mechanism compared to that of non-stress. BLAST searches of the flanking
sequences of the associated loci against DNA databases revealed several stress
responsive genes linked to the drought resistance loci, including leucine-rich
repeat receptor-like kinase, B3 DNA-binding domain protein, translation
initiation factor IF2, and phospholipase-like protein. With further
investigation, those markers closely linked to drought resistance can be used for
MAS to accelerate the development of new alfalfa cultivars with improved
resistance to drought and other abiotic stresses.
PMID- 28706533
TI - Inhibition of Histone H3K9 Methylation by BIX-01294 Promotes Stress-Induced
Microspore Totipotency and Enhances Embryogenesis Initiation.
AB - Microspore embryogenesis is a process of cell reprogramming, totipotency
acquisition and embryogenesis initiation, induced in vitro by stress treatments
and widely used in plant breeding for rapid production of doubled-haploids, but
its regulating mechanisms are still largely unknown. Increasing evidence has
revealed epigenetic reprogramming during microspore embryogenesis, through DNA
methylation, but less is known about the involvement of histone modifications. In
this study, we have analyzed the dynamics and possible role of histone H3K9
methylation, a major repressive modification, as well as the effects on
microspore embryogenesis initiation of BIX-01294, an inhibitor of histone
methylation, tested for the first time in plants, in Brassica napus and Hordeum
vulgare. Results revealed that microspore reprogramming and initiation of
embryogenesis involved a low level of H3K9 methylation. With the progression of
embryogenesis, methylation of H3K9 increased, correlating with gene expression
profiles of BnHKMT SUVR4-like and BnLSD1-like (writer and eraser enzymes of
H3K9me2). At early stages, BIX-01294 promoted cell reprogramming, totipotency and
embryogenesis induction, while diminishing bulk H3K9 methylation. DNA methylation
was also reduced by short-term BIX-01294 treatment. By contrast, long BIX-01294
treatments hindered embryogenesis progression, indicating that H3K9 methylation
is required for embryo differentiation. These findings open up new possibilities
to enhance microspore embryogenesis efficiency in recalcitrant species through
pharmacological modulation of histone methylation by using BIX-01294.
PMID- 28706534
TI - Bag of Visual Words Model with Deep Spatial Features for Geographical Scene
Classification.
AB - With the popular use of geotagging images, more and more research efforts have
been placed on geographical scene classification. In geographical scene
classification, valid spatial feature selection can significantly boost the final
performance. Bag of visual words (BoVW) can do well in selecting feature in
geographical scene classification; nevertheless, it works effectively only if the
provided feature extractor is well-matched. In this paper, we use convolutional
neural networks (CNNs) for optimizing proposed feature extractor, so that it can
learn more suitable visual vocabularies from the geotagging images. Our approach
achieves better performance than BoVW as a tool for geographical scene
classification, respectively, in three datasets which contain a variety of scene
categories.
PMID- 28706535
TI - Which Factors Are Important for Successful Sentinel Node Navigation Surgery in
Gastric Cancer Patients? Analysis from the SENORITA Prospective Multicenter
Feasibility Quality Control Trial.
AB - BACKGROUND: We investigated the results of quality control study prior to phase
III trial of sentinel lymph node navigation surgery (SNNS). METHODS: Data were
reviewed from 108 patients enrolled in the feasibility study of laparoscopic
sentinel basin dissection (SBD) in gastric cancer. Seven steps contain tracer
injection at submucosa (step 1) and at four sites (step 2) by intraoperative
esophagogastroduodenoscopy (EGD), leakage of tracer (step 3), injection within 3
minutes (step 4), identification of at least one sentinel basin (SB) (step 5),
evaluation of sentinel basin nodes (SBNs) by frozen biopsy (step 6), and
identification of at least five SBNs at back table and frozen sections (step 7).
RESULTS: Failure in step 7 (n = 23) was the most common followed by step 3 (n =
15) and step 6 (n = 13). We did not find any differences of clinicopathological
factors between success and failure group in steps 1~6. In step 7, body mass
index (BMI) was only the significant factor. The success rate was 97.1% in
patients with BMI < 23 kg/m2 and 80.3% in those with BMI >= 23 kg/m2 (P =
0.028). CONCLUSIONS: Lower BMI group showed higher success rate in step 7.
Surgeons doing SNNS should be cautious when evaluating sufficient number of SBN
in obese patients.
PMID- 28706536
TI - The Videofluorographic Swallowing Study in Rheumatologic Diseases: A
Comprehensive Review.
AB - Autoimmune connective tissue diseases are a heterogeneous group of pathologies
that affect about 10% of world population with chronic evolution in 20%-80%.
Inflammation in autoimmune diseases may lead to serious damage to other organs
including the gastrointestinal tract. Gastrointestinal tract involvement in these
patients may also due to both a direct action of antibodies against organs and
pharmacological therapies. Dysphagia is one of the most important symptom, and it
is caused by failure of the swallowing function and may lead to aspiration
pneumonia, malnutrition, dehydration, weight loss, and airway obstruction. The
videofluorographic swallowing study is a key diagnostic tool in the detection of
swallowing disorders, allowing to make an early diagnosis and to reduce the risk
of gastrointestinal and pulmonary complications. This technique helps to identify
both functional and structural anomalies of the anatomic chain involved in
swallowing function. The aim of this review is to systematically analyze the
basis of the pathological involvement of the swallowing function for each
rheumatological disease and to show the main features of the videofluorographic
study that may be encountered in these patients.
PMID- 28706537
TI - Can Human Embryonic Stem Cell-Derived Stromal Cells Serve a Starting Material for
Myoblasts?
AB - A large number of myocytes are necessary to treat intractable muscular disorders
such as Duchenne muscular dystrophy with cell-based therapies. However, starting
materials for cellular therapy products such as myoblasts, marrow stromal cells,
menstrual blood-derived cells, and placenta-derived cells have a limited lifespan
and cease to proliferate in vitro. From the viewpoints of manufacturing and
quality control, cells with a long lifespan are more suitable as a starting
material. In this study, we generated stromal cells for future myoblast therapy
from a working cell bank of human embryonic stem cells (ESCs). The ESC-derived
CD105+ cells with extensive in vitro proliferation capability exhibited
myogenesis and genetic stability in vitro. These results imply that ESC-derived
CD105+ cells are another cell source for myoblasts in cell-based therapy for
patients with genetic muscular disorders. Since ESCs are immortal, mesenchymal
stromal cells generated from ESCs can be manufactured at a large scale in one lot
for pharmaceutical purposes.
PMID- 28706538
TI - Safety of 100 ug venom immunotherapy rush protocols in children compared to
adults.
AB - BACKGROUND: There is a paucity of studies examining the safety of venom
immunotherapy (VIT) in children. We aimed to assess the incidence of anaphylactic
side effects during rush VIT in a cohort of pediatric patients and adult
controls. METHODS: 72 consecutive cycles of VIT-buildup in 71
children/adolescents aged 7-17 years were retrospectively evaluated and compared
to an adult control group (n = 981) with regard to baseline parameters (sex,
causative venom, severity of index sting reaction, results of allergy testing,
comorbidities) and the incidence of anaphylactic adverse reactions. RESULTS:
Compared to adults, severe index sting-induced anaphylaxis was significantly less
common in children (P = .001). Children were more likely to suffer from bee venom
allergy (P < .001) and showed higher levels of bee venom-specific IgE (P = .013),
but lower serum tryptase concentrations (P = .014). The overall rate of VIT
induced anaphylactic reactions was higher in children than in adults (6.9% vs
2.5%, P = .046 by univariate analysis). In the final binary logistic regression
model, however, only bee VIT (P = .039; odds ratio 2.25; confidence interval 1.04
4.87) and 5-day compared to 3-day buildup protocols (P = .011; odds ratio 2.64;
confidence interval 1.25-5.57) were associated with an increased risk of
treatment-induced anaphylaxis. All pediatric patients finally reached and
tolerated the target maintenance dose of 100 ug. CONCLUSIONS: The higher
anaphylactic reaction rate observed in pediatric patients may be attributed to a
greater prevalence of bee venom allergy. VIT-induced anaphylaxis in children is
usually mild and does not affect further updosing and maintenance of VIT.
PMID- 28706539
TI - Assessment of Barriers for Midwives to Achieve Professional Management Positions
from Midwives' Point of View.
AB - BACKGROUND: Despite the effects of midwives on the health of family and community
through promotion of maternal and child health indicators, they are not in the
position of professional decision making. Therefore, this study was aimed to
determine the barriers to achieve professional management positions by midwives.
MATERIALS AND METHODS: This study was a descriptive and cross-sectional study.
The members of board commission of midwifery and reproductive health, the
academic members of midwifery department and midwives working at the adjutancy of
health and treatment were selected from eight Iranian universities of medical
sciences. Data was collected through demographic characteristics questionnaire, a
researcher-made questionnaire about administrative barriers, and management
skills. Validity and reliability of this tool was confirmed through content
validity and Cronbach's alpha coefficient, and the results were analyzed using
inferential statistics (analysis of variance and Kruskal-Wallis test). RESULTS:
The results of this study showed that the barriers for midwives to achieve
professional management positions in order of preference were organizational
barriers (71.4%), cultural barriers (42.4%), and individual barriers (30.8%).
CONCLUSIONS: Based on the findings of this research, organizational barriers are
the most important obstacle to achieve professional management positions.
Therefore, the role of the authorities is emphasized to eliminate organizational
barriers and provide more resources to reduce this problem.
PMID- 28706540
TI - The Relationship between Dignity Status and Quality of Life in Iranian Terminally
Ill Patients with Cancer.
AB - BACKGROUND: Palliative care is an approach that has been used to care for
terminally ill patients. The current study was performed to assess the
association between the status of patient dignity and quality of life (QOL) in
Iranian terminally ill patients with cancer. MATERIALS AND METHODS: This
descriptive correlational study was conducted on 210 end-stage cancer patients
(102 men and 108 women) who were referred to Seyed Al-Shohada Hospital, Isfahan,
Iran, in 2015. To assess dignity status, we used the Patient Dignity Inventory.
The Persian version of the European Organization for Research and Treatment of
Cancer Quality of Life Questionnaire was used for QOL assessment. RESULTS: There
was a significant negative association between total dignity status and QOL
scales. In addition, significant negative relationship was observed between
dignity-related domains (loss of worth sense: r = -0.50, P < 0.001; anxiety and
uncertainty: r = -0.51, P < 0.001; symptom distress: r = -0.62, P < 0.001; and
loss of autonomy: r = -0.61, P < 0.001) and functional scale and some subscales
of the QOL scale. In contrast, a significant positive relationship was found
between dignity-related domains, and total symptom scale and fatigue. No
significant relationship was observed between different items of dignity and
global health status/QOL scale. CONCLUSIONS: High dignity status in terminally
ill patients was associated with higher QOL in terms of functional intactness and
lower symptom distress. Further studies are necessary to shed light to our
findings.
PMID- 28706541
TI - Assessment of Iranian Nurses and Emergency Medical Personnel in Terms of
Cardiopulmonary Resuscitation Knowledge Based on the 2010 Guideline.
AB - BACKGROUND: The aim of this study was to compare the cardiopulmonary
resuscitation (CPR) knowledge of hospital nurses and emergency medical personnel
in Kermanshah, Iran. MATERIALS AND METHODS: This descriptive cross-sectional
study was conducted on 330 hospital nurses and 159 emergency medical personnel
working in educational hospitals and emergency medical centers in Kermanshah.
Data were collected using a validated and reliable (r = 0.74) researcher-made
questionnaire consisting of a demographic characteristics questionnaire and the
2010 CPR knowledge questionnaire. RESULTS: Based on the most recent CPR
guidelines, the knowledge of 19.5%, 78.6%, and 1.9% of the emergency medical
staff was excellent, good, and moderate, respectively. None of the participants
had poor knowledge. In addition, the knowledge of 20.2%, 65.4%, 14%, and 0.4% of
the nurses in this study was excellent, good, moderate, and poor, respectively.
There was no significant difference in CPR knowledge between hospital nurses and
emergency medical staff. Moreover, no significant association was found between
CPR knowledge and gender, age, work experience, field of study, previous
occupation, and advanced resuscitation courses. However, CPR knowledge of
individuals with training in basic CPR courses was higher than participants
without training in these courses (P < 0.05). CONCLUSIONS: Based on the findings
of this study, CPR knowledge among Iranian nurses and emergency medical personnel
was in an acceptable range. Nevertheless, it is strongly recommended that nurses
and emergency staff receive training according to the most recent CPR guidelines.
PMID- 28706542
TI - Effect of Fordyce's Happiness Program on Stress, Anxiety, and Depression among
the Patients Undergoing Hemodialysis.
AB - BACKGROUND: Patients with end-stage renal disease on hemodialysis are affected by
psychological stressors, which contribute to poor quality of life and negative
clinical outcomes. Stress, anxiety, and depression are highly prevalent in this
population. Fordyce's happiness program has been believed to be one of the
complementary therapies that could promote psychological wellbeing. The goal of
this study was to evaluate the effects of Fordyce's happiness program on the
stress, anxiety, and depression in patients with hemodialysis. MATERIALS AND
METHODS: This is a clinical trial. A total of 50 patients undergoing hemodialysis
were randomly recruited into the study group (n = 25) and the control group (n =
25). Intervention of Fordyce's happiness program was administrated for 20 minutes
during hemodialysis sessions once a week for 6 sessions. For the control group, 3
sessions were held by the researcher's colleague through communication, dialogue,
and listening to the patients' problems individually. The data was collected by
the Stress, Anxiety and Depression (DASS-21) questionnaire. RESULTS: There was a
significant difference in the mean scores of stress, anxiety, and depression in
the intervention group before immediately after and one month after intervention
(P < 0.05), whereas there was no significant difference in the mean scores of
stress, anxiety, and depression before, immediately after, and 1 month after
intervention in control group. CONCLUSIONS: The obtained results showed that
Fordyce Happiness Training Program can reduce the stress, anxiety, and depression
in patients treated with hemodialysis.
PMID- 28706543
TI - A Comparison of the Effect of Education through Video versus Demonstration on
Fear of Falling in Nursing Home Residents of Mashhad, Iran.
AB - BACKGROUND: Fear of falling is one of the most serious potential health problems.
This issue is of high importance in the elderly with serious consequences such as
limitations in daily activities, gait imbalance, social isolation, and increased
risk of falling. One way to resolve this problem is the use of modern teaching
methods such as demonstration and videos. The present study aimed at comparing
the effect of education through video versus demonstration on fear of falling in
nursing home residents of Mashhad city, Iran. MATERIALS AND METHODS: This quasi
experimental study (with pre-test and post-test) was performed among 66 elderly
residents of nursing homes in Mashhad. The participants were randomly divided
into two groups of demonstration and video. Then, they received training using
the abovementioned methods. The participants' level of fear of falling was
measured through Fall Efficacy Scale. RESULTS: After the intervention, mean
scores of the fear of falling were 47.50 and 49.84 in demonstration and video
groups, respectively. As indicated by the results, after the intervention,
participants' fear of falling decreased by 23.7% and 20.7% in demonstration and
video groups, respectively. This difference is statistically significant (P =
0.001). CONCLUSIONS: Training through video methods reduces the fear of falling
in the elderly. Because of the special conditions of the elderly, the video
training method may require more consideration due to its lower costs and easier
performance.
PMID- 28706544
TI - The Effect of a Communicational Program on Psychological Distress in the Elderly
Suffering from Cancer.
AB - BACKGROUND: Psychological distress is one of the most common psychological
symptoms in elderly cancer patients. However, many of these patients do not
receive any treatment for distress management. Therefore, we aimed to assess the
effect of a communication program on the psychological distress of elderly cancer
patients. MATERIALS AND METHODS: This two-group clinical trial with a before and
after design was conducted in Al-Zahra and Seyed-Al-Shohada hospitals affiliated
to the Isfahan University of Medical Sciences in 2015. A total of 64 elderly
patients were randomly assigned to two groups: experimental and control groups. A
3-week intervention (communicational program) consisting of distributing
educational booklets, practices, and phone follow-ups was performed for the
intervention group. All sessions were held during the 3-week period with sessions
held twice per week both in the form of personal attendance and phone tracking,
and the patients were encouraged to do the tasks assigned to them. The control
group received routine care, and at the end of the study, the content of the
sessions was explained to them. The demographic and clinical data of the
participants were recorded, and all participants completed Kessler's
Psychological Distress inventory at baseline and at the end of the 3-week
intervention. RESULTS: We found a significant difference in the psychological
distress scores between the two groups before and after the intervention (P <
0.001, independent t-test). Moreover, the mean psychological distress scores
decreased significantly in the experimental group after the intervention (P <
0.001, paired t-test). CONCLUSIONS: Our communicational program had a positive
effect on psychological distress in elderly patients with cancer. Therefore, this
program could be used as an easy, cheap, and practical approach for reducing
psychological distress in these patients.
PMID- 28706545
TI - Effect of Face-to-face Education, Problem-based Learning, and Goldstein
Systematic Training Model on Quality of Life and Fatigue among Caregivers of
Patients with Diabetes.
AB - BACKGROUND: Education is a fundamental component for patients with diabetes to
achieve good glycemic control. In addition, selecting the appropriate method of
education is one of the most effective factors in the quality of life. The
present study aimed to evaluate the effect of face-to-face education, problem
based learning, and Goldstein systematic training model on the quality of life
(QOL) and fatigue among caregivers of patients with diabetes. MATERIALS AND
METHODS: This randomized clinical trial was conducted in Hajar Hospital
(Shahrekord, Iran) in 2012. The study subjects consisted of 105 family caregivers
of patients with diabetes. The participants were randomly assigned to three
intervention groups (35 caregivers in each group). For each group, 5-h training
sessions were held separately. QOL and fatigue were evaluated immediately before
and after the intervention, and after 1, 2, 3, and 4 months of intervention.
RESULTS: There was a significant increase in QOL for all the three groups. Both
the problem-based learning and the Goldstein method showed desirable QOL
improvement over time. The desired educational intervention for fatigue reduction
during the 4-month post-intervention period was the Goldstein method. A
significant reduction was observed in fatigue in all three groups after the
intervention (P < 0.001). CONCLUSIONS: The results of the present study
illustrated that the problem-based learning and Goldstein systematic training
model improve the QOL of caregivers of patients with diabetes. In addition, the
Goldstein systematic training model had the greatest effect on the reduction of
fatigue within 4 months of the intervention.
PMID- 28706546
TI - The Impact of a Neonatal Sleep Care Training Program on Nurses' Knowledge and
Performance in Neonatal Intensive Care Units.
AB - BACKGROUND: Sleep is essential for organizing and maturation of the brain in
premature infants; it also plays a role in maintaining the natural balance
between different nervous centers. Given the role of nurses in neonatal sleep
care, this study aimed at assessing the impact of a training program on the
nurses' knowledge and performance in a Neonatal Intensive Care Unit (NICU).
MATERIALS AND METHODS: In this quasi-experimental study which structured into
three stages, 35 nurses working in an NICU in Isfahan, Iran, were included. The
neonatal sleep training program was in the form of a lecture with questions and
answers and then placing posters and booklets in the NICU. The data were
collected by a questionnaire for nurses' knowledge and performance assessment
which its validity and reliability were determined through content validity and
internal consistency, respectively. The nurses' knowledge was assessed via 40
multiple-choice questions before, immediately after, and 1 month after the
training program, and their performance was evaluated before and 1 month after
intervention using 15 multiple-choice questions. The data were analyzed by
descriptive and inferential statistics using the SPSS software version 16.
RESULTS: The results showed that the mean score of nurses' knowledge after
training has significantly increased as compared to before training (33.33 (4.4)
vs. 19.33 (4.1)) (P < 0.001); however, the score of performance was slightly
improved although it did not reveal any significant differences (P = 0.07, 42.6
(7.6) vs. 45.1 (7.8)). CONCLUSIONS: The results indicated that this method of
training program could lead to an increase in nurses' knowledge, but it did not
significantly improve their performance. It may be due to a low number of
training sessions; therefore, it is recommended to implement long-term training
programs in this field.
PMID- 28706547
TI - Factors Related to Women's Childbirth Satisfaction in Physiologic and Routine
Childbirth Groups.
AB - BACKGROUND: Women's satisfaction with childbirth is an important measure of the
quality of maternity care services. This study aims to address factors related to
women's childbirth satisfaction in physiological and routine childbirth groups.
MATERIALS AND METHODS: This descriptive-analytical study was conducted among 340
women in physiological and routine childbirth groups in 2012. Women were selected
through convenience sampling method in the routine group and by census in the
physiological group. Data were collected using a 5-part questionnaire composed of
demographic and obstetrics details, Mackey's Childbirth Satisfaction Rating Scale
(CSRS), satisfied with birth setting, Labor Agentry Scale (LAS), and Visual
Analogue Scale (VAS), which was completed by interview 24 hours after childbirth.
Data were analyzed using the Statistical Package for the Social Sciences version
18 software using Pearson correlation test, independent t-test, analysis of
variance, and linear, multivariate regression model at the significant level of P
< 0.05. RESULTS: In both the physiological and routine childbirth groups,
satisfaction was found related to the severity of pain (P < 0.05), self-control
(P < 0.0001), and birth setting satisfaction (P < 0.0001). In the physiological
group, satisfaction was significantly related to previous knowledge of childbirth
(P = 0.024), attitude toward the recent pregnancy (P = 0.007), and perceived
severity of pain (P = 0.016). However, in the routine group, satisfaction was
related only to intentional pregnancy (P = 0.002). In neither group, satisfaction
was related to demographic characteristics, maternal parity, and participation in
pregnancy and childbirth classes or maternal feelings toward the onset of
childbirth (P > 0.05). CONCLUSIONS: Improved physical structure and setting of
birth room, nonmedical pain relief, mothers' involvement in the process of labor,
and sense of being in control are associated with mothers' satisfaction.
PMID- 28706548
TI - The Effect of Continuous Care on the Lifestyle of Patients with Multiple
Sclerosis: A Randomized Clinical Trial.
AB - BACKGROUND: Multiple sclerosis is a common debilitating chronic disease of the
central nervous system with a progressive and prolonged nature. Patients need an
adjusted lifestyle and continuous care in order to prevent its recurrence and
progressive disabilities. This study aimed to assess the effect of continuous
care on lifestyle in patients suffering from multiple sclerosis. MATERIALS AND
METHODS: A randomized clinical trial was conducted among 72 patients with
multiple sclerosis who referred to the Farshchian Educational Hospital in
Hamadan, Iran in 2013. The patients were allocated to intervention and control
groups using balanced block randomization with blocks of four. The steps of
continuous care (orientation, sensitization, control, and evaluation) were
implemented in the case group for 2 months. The patients' lifestyle was assessed
before and 1 and 2 months after continuous care using the researcher-developed
Lifestyle Questionnaire. The data were analyzed using the Chi-square test, t
test, and repeated-measures analysis of variance. RESULTS: The mean score of
lifestyle and its dimensions were significantly higher in the intervention group
1 and 2 months after the intervention compared to the baseline (P = 0.001). In
contrast, the mean score of lifestyle and its dimensions had no significant
difference in the control group 1 and 2 months after routine care compared to the
baseline. CONCLUSIONS: Continuous care improved the patients' lifestyle. It could
be designed as an appropriate care system into the hospitals or other health care
centers. This care system could be used widely in order to improve adherence to
suitable lifestyle in patients with chronic diseases.
PMID- 28706549
TI - Nurses' Experiences of Caring for Patients with Different Cultures in Mashhad,
Iran.
AB - BACKGROUND: Mashhad is a center of diverse cultures, where many local and foreign
cultures live together in its context. One of the main needs of a society with
cultural diversity is transcultural care of patients. Hence, the present study
took the first step for care of culturally diversified and minority patients in
Mashhad. This research has been conducted to explore the nurses' experience of
caring from patients with different cultures. MATERIALS AND METHODS: This study
is a qualitative research using phenomenological hermeneutics approach. The
participations include nurses who have been working 5 or less than 5 years in the
hospitals affiliated to Medical University of Mashhad. They were selected using
purposeful sampling method. For data collection, semi-structured, in-depth
interview was used. For data analysis, interpretation method was used. The
interviews continued until saturation of data was obtained. RESULTS: Data
analysis resulted in extraction of 4 themes including ethnocentrism,
contradicting perceptions of care, it is not our fault, and lack of cultural
knowledge. CONCLUSIONS: The experience of nurses in taking care of patients with
other cultures showed that minorities and small cultures have been neglected in
Mashhad and hospitalization of such people in hospitals and other clinics is not
specific. We recommend that an educational curriculum about transcultural care
should be added to nursing courses. Also, necessary equipment and facilities
should be considered and prepared for culturally different patients in hospitals.
PMID- 28706550
TI - Effect of Acupressure on Early Complications of Menopause in Women Referring to
Selected Health Care Centers.
AB - BACKGROUND: Menopausal period is accompanied by numerous disorders and
complications. Nowadays, hormone therapy is the most effective existing method to
treat these complications, but many women cannot undergo that due to the known
potentiality of risk. So, the present study aimed to investigate the effect of
acupressure on early complications of menopause. MATERIALS AND METHODS: This is a
blind random clinical trial conducted on 70 menopaused women referring to
selected health care centers in Tehran who were qualified to enter the study. The
subjects were randomly assigned to study (wearing a special acupressure wrist
brace, three times a week for 15 min, in both bands on Shenmen and Sanyinjiao
acupoints, in addition to receiving conventional menopausal care) and placebo
(wearing a special acupressure wrist brace, three times a week for 15 min, but in
a counter wise way, in addition to receiving conventional menopausal care)
groups. Length of intervention was 4 weeks. Early complications of menopause were
evaluated before intervention and 2 and 4 weeks after intervention in both
groups. Data were analyzed by descriptive and inferential statistical methods.
RESULTS: The findings revealed a significant reduction in the number and severity
of hot flashes, the number of night sweats, and state-trait anxiety severity (P <
0.001), but with regard to the severity of night sweats and trait anxiety, there
was no significant difference between groups. CONCLUSIONS: With regard to the
obtained results on the effect of acupressure on reduction of early menopausal
complications, acupressure along with conventional menopausal care is suggested
as one of the complementary medicine methods to improve the complications of this
period.
PMID- 28706551
TI - Informal Caregivers' Experiences of Caring of Multiple Sclerosis Patients: A
Qualitative Study.
AB - BACKGROUND: Approximately one-third of people suffering from multiple sclerosis
(MS) need long-term care by their families, however, we know little of their
experiences. Exploring these experiences can be a guideline to improve the
quality of care for MS patients. The goal of this study is to explore informal
caregivers' experiences regarding care of MS patients. MATERIALS AND METHODS: A
qualitative content analysis method was used to conduct this study in 2014. The
study participants were 23 informal caregivers of MS patients who were chosen by
purposeful sampling from the MS association of Iran. Data was analyzed by content
analysis. RESULTS: The analysis resulted in the emergence of six themes and
seventeen subthemes. The main themes were being plagued, mental health damage,
being captive among obstacles, perception of the affected family, being an
emotional supporter, and need to maintain the functional independence of the
patient. CONCLUSIONS: The findings represent the mean of long-term care by
informal caregivers of MS patients, as well as the needs and challenges of this
relationship. The findings can serve to create a framework for developing nursing
care processes and planning educational sessions and support programs for MS
patients and their informal caregivers.
PMID- 28706552
TI - Evaluating the Effect of Lifestyle Education Based on Health Belief Model for
Mothers of Obese and Overweight School-age Children on Obesity-Related Behaviors.
AB - BACKGROUND: Nowadays, childhood obesity is a matter of significant concern
because of its negative effects on personal health and harmful socioeconomic
consequences. The purpose of the present study was to evaluate the effectiveness
of lifestyle education based on the health belief model for mothers of obese and
overweight school-age children on obesity-related behaviors. MATERIALS AND
METHODS: In this quasi-experimental study, 64 obese and overweight elementary
students and their mothers who met the inclusion criteria participated. The
participants were randomly categorized into two groups (experimental and
control). The experimental group received the considered interference, which
consisted of four educational sessions based on the health belief model. Data
collection tool was a standard questionnaire. The questionnaire filled by the
participants during interviews conducted before, immediately after, and two
months after the intervention. Data were analyzed using Mann-Whitney, Chi-square,
student's t-test, repeated-measures analysis of variance, and least significant
difference tests. RESULTS: Mean scores of obesity-related behavior before the
intervention were not significantly different between the experimental and
control group (53.41 (6.78). vs 54.72 (4.63); P = 0.37), however, were different
immediately after (58.41 (6.88) vs 54.81 (4.66); P = 0.02) and two months after
the intervention (62.34 (8.62) vs 55.84 (7.59); P = 0.002). CONCLUSIONS: This
study indicated the effectiveness of lifestyle education based on the health
belief model for improving obesity-related behaviors. Therefore, the use of this
educational program is recommended for mothers.
PMID- 28706553
TI - Educational Needs of Women in Relation to Postpartum Religious Orders.
AB - INTRODUCTION: Religious orders are one of the educational needs of the postpartum
period. This study was conducted to determine the educational needs of postpartum
religious orders. MATERIALS AND METHODS: This cross-sectional study was conducted
among 421 postpartum women and 15 specialists. Quota random sampling was
conducted from January to March 2014 in Isfahan, Iran. Data analysis was
performed using the Statistical Package for the Social Sciences software and
statistical methods. RESULTS: From the perspective of women and specialists, the
results showed that the educational needs of women in postpartum religious orders
is high. CONCLUSION: Considering the high educational need in the field of
postpartum religious orders, it is necessary to integrate education in prenatal
and postnatal health education programs.
PMID- 28706554
TI - Sexual Knowledge and Attitude among Girls Who are Getting Married Based on the
Information from Yas Pre-marriage Counseling Center.
AB - BACKGROUND: High prevalence of sexual dysfunction results from inadequate
knowledge or inappropriate attitude toward the natural phenomenon of sexual
desire. This study aimed to define sexual knowledge and attitude among girls who
were getting married and referred to Yas pre-marriage counseling center.
MATERIALS AND METHODS: This research was a descriptive analytical study. The
information of 165 girls, who were about to get married, were collected through
convenient sampling using a researcher-made questionnaire. Data were analyzed
using SPSS version 16 software. Inferential statistical method and Pearson
correlation were used for data analysis. RESULTS: Results showed that the mean
scores of sexual knowledge and attitude among the participants were 57.42 and
69.02, respectively. There was a significant association between the mean scores
of sexual knowledge and sexual attitude (P < 0.001, r = 0.63). CONCLUSIONS:
Results showed that the participants had relatively appropriate knowledge and
attitude toward sexual relationship.
PMID- 28706555
TI - Advances in iron chelation therapy: transitioning to a new oral formulation.
AB - Iron overload is a concern for patients who require repeated red-blood-cell
transfusions due to conditions such as sickle cell disease, thalassemia, or
myelodysplastic syndromes. The recommended treatment for removing excess iron in
these patients is iron chelation therapy. Currently available iron chelators
include deferoxamine, which is administered by injection, and deferasirox and
deferiprone, both of which are administered orally. Adherence to iron chelator
therapy is an important consideration and may be affected by side effects. A new
formulation of deferasirox, a film-coated tablet (FCT), has the potential to
improve adherence by offering greater flexibility in administration compared with
the original formulation of deferasirox, a dispersible tablet (DT) for oral
suspension. This review provides an overview of the currently available iron
chelator formulations, with a focus on a comparison between deferasirox DT for
oral suspension and deferasirox FCT. The new formulation may be associated with
fewer side effects and has increased bioavailability. In addition, alternative
strategies for iron chelation, such as combining two different iron chelators,
will be discussed.
PMID- 28706556
TI - Corrigendum: Pharmacoeconomic comparison of aripiprazole once-monthly and
paliperidone palmitate from a head-to-head clinical trial in schizophrenia: a US
analysis.
AB - [This corrects the article on p. 212301 in vol. 5, PMID: 27708677.].
PMID- 28706557
TI - Comparative Pharmacokinetics and Bioavailability of Three Ephedrines in Rat after
Oral Administration of Unprocessed and Honey-Fried Ephedra Extract by Response
Surface Experimental Design.
AB - Ephedra have been used as a common traditional Chinese medicine for thousands of
years. However, the perspiration effect of the unprocessed ephedra was too
strong. Clinical trials have shown that processing methods play a critical role
in moderating the perspiration property of ephedra according to the needs. A LC
MS/MS method was developed and validated to compare the pharmacokinetic
properties of the three ephedrines after oral administration of unprocessed and
honey-fried ephedra extract. The contents of honey, frying temperature, and
frying time were set at 20%, 116 degrees C, and 7 min by the Box-Behnken response
surface method, respectively. In the pharmacokinetics study, the biosamples were
pretreated and extracted by protein precipitation method with acetonitrile and
separated on an Agilent TC-C18 column (250 mm * 4.6 mm, 5 MUm) using a mobile
phase consisting of 0.1% formic acid methanol and 5 mM ammonium acetate aqueous
solution (5 : 95, v/v). All calibration curves were linear (r > 0.9932) with
lower limits of quantitation (LLOQs) < 12 ng/mL. The mean recoveries of the three
analytes were higher than 75%. The pharmacokinetics study indicated that the
reduced absorption of ephedrine hydrochloride (EH) and pseudoephedrine
hydrochloride (PEH) in honey-fried ephedra group might be the main reason for the
moderation of the diaphoretic property.
PMID- 28706558
TI - Qiliqiangxin Enhances Cardiac Glucose Metabolism and Improves Diastolic Function
in Spontaneously Hypertensive Rats.
AB - Cardiac diastolic dysfunction has emerged as a growing type of heart failure. The
present study aims to explore whether Qiliqiangxin (QL) can benefit cardiac
diastolic function in spontaneously hypertensive rat (SHR) through enhancement of
cardiac glucose metabolism. Fifteen 12-month-old male SHRs were randomly divided
into QL-treated, olmesartan-treated, and saline-treated groups. Age-matched WKY
rats served as normal controls. Echocardiography and histological analysis were
performed. Myocardial glucose uptake was determined by 18F-FDG using small-animal
PET imaging. Expressions of several crucial proteins and key enzymes related to
glucose metabolism were also evaluated. As a result, QL improved cardiac
diastolic function in SHRs, as evidenced by increased E'/A'and decreased E/E' (P
< 0.01). Meanwhile, QL alleviated myocardial hypertrophy, collagen deposits, and
apoptosis (P < 0.01). An even higher myocardial glucose uptake was illustrated in
QL-treated SHR group (P < 0.01). Moreover, an increased CS activity and ATP
production was observed in QL-treated SHRs (P < 0.05). QL enhanced cardiac
glucose utilization and oxidative phosphorylation in SHRs by upregulating
AMPK/PGC-1alpha axis, promoting GLUT-4 expression, and regulating key enzymes
related to glucose aerobic oxidation such as HK2, PDK4, and CS (P < 0.01). Our
data suggests that QL improves cardiac diastolic function in SHRs, which may be
associated with enhancement of myocardial glucose metabolism.
PMID- 28706559
TI - Insights into the Roles of Midazolam in Cancer Therapy.
AB - With its high worldwide mortality and morbidity, cancer has gained increasing
attention and novel anticancer drugs have become the focus for cancer research.
Recently, studies have shown that most anesthetic agents can influence the
activity of tumor cells. Midazolam is a gamma-aminobutyric acid A (GABAA)
receptor agonist, used widely for preoperative sedation and as an adjuvant during
neuraxial blockade. Some studies have indicated the potential for midazolam as a
novel therapeutic cancer drug; however, the mechanism by which midazolam affects
cancer cells needs to be clarified. This systematic review aims to summarize the
progress in assessing the molecular mechanism of midazolam as an anticancer
agent.
PMID- 28706560
TI - Experimental realization and characterization of an electronic Lieb lattice.
AB - Geometry, whether on the atomic or nanoscale, is a key factor for the electronic
band structure of materials. Some specific geometries give rise to novel and
potentially useful electronic bands. For example, a honeycomb lattice leads to
Dirac-type bands where the charge carriers behave as massless particles [1].
Theoretical predictions are triggering the exploration of novel 2D geometries [2
10], such as graphynes, Kagome and the Lieb lattice. The latter is the 2D
analogue of the 3D lattice exhibited by perovskites [2]; it is a square-depleted
lattice, which is characterised by a band structure featuring Dirac cones
intersected by a flat band. Whereas photonic and cold-atom Lieb lattices have
been demonstrated [11-17], an electronic equivalent in 2D is difficult to realize
in an existing material. Here, we report an electronic Lieb lattice formed by the
surface state electrons of Cu(111) confined by an array of CO molecules
positioned with a scanning tunneling microscope (STM). Using scanning tunneling
microscopy, spectroscopy and wave-function mapping, we confirm the predicted
characteristic electronic structure of the Lieb lattice. The experimental
findings are corroborated by muffin-tin and tight-binding calculations. At higher
energies, second-order electronic patterns are observed, which are equivalent to
a super-Lieb lattice.
PMID- 28706561
TI - Automatic Detection of Epilepsy and Seizure Using Multiclass Sparse Extreme
Learning Machine Classification.
AB - An automatic detection system for distinguishing normal, ictal, and interictal
electroencephalogram (EEG) signals is of great help in clinical practice. This
paper presents a three-class classification system based on discrete wavelet
transform (DWT) and the nonlinear sparse extreme learning machine (SELM) for
epilepsy and epileptic seizure detection. Three-level lifting DWT using
Daubechies order 4 wavelet is introduced to decompose EEG signals into delta,
theta, alpha, and beta subbands. Considering classification accuracy and
computational complexity, the maximum and standard deviation values of each
subband are computed to create an eight-dimensional feature vector. After
comparing five multiclass SELM strategies, the one-against-one strategy with the
highest accuracy is chosen for the three-class classification system. The
performance of the designed three-class classification system is tested with
publicly available epilepsy dataset. The results show that the system achieves
high enough classification accuracy by combining the SELM and DWT and reduces
training and testing time by decreasing computational complexity and feature
dimension. With excellent classification performance and low computation
complexity, this three-class classification system can be utilized for practical
epileptic EEG detection, and it offers great potentials for portable automatic
epilepsy and seizure detection system in the future hardware implementation.
PMID- 28706562
TI - Psychological health and religious coping of Ghanaian women with infertility.
AB - BACKGROUND: Infertility has been shown to have considerable psychological effects
on the well-being of couples, especially women. Religion has been found as a
resource used by infertile women to cope with their distress. Little research has
examined the influence of religious coping on psychological distress among
infertile women in Ghana. This study examines the relationship between positive
and negative religious coping and psychological health for women with infertility
problems in Ghana. METHODS: One hundred and fifty married women who were
receiving assisted reproduction care in two specialized clinics were recruited
for this study. Participants were administered with the Brief Symptom Inventory
and Brief Religious Coping Scale to assess psychological health associated with
infertility and religious coping respectively. A hierarchical regression was
performed to examine the relative contribution of the domains of psychological
health (i.e. somatization, anxiety and depression) in predicting negative
religious coping and positive religious. RESULTS: The results showed that
negative religious coping was significant and positively correlated with
somatization, depression and anxiety. Furthermore, a positive relationship also
existed between positive religious coping and somatization and anxiety but not
depression. After controlling for age and duration of infertility, somatization
and anxiety predicted positive religious coping whilst all the domains of
psychological health (somatization, anxiety and depression) precited negative
religious coping. CONCLUSIONS: This study expanded on the existing literature by
examining positive and negative religious coping with psychological distress
associated with infertility for women. These results underscore the need for
health professionals providing therapies for women with infertility to
acknowledge and consider their religious beliefs as this influences their mental
health.
PMID- 28706563
TI - Quality of life in children and adolescents with bipolar I depression treated
with olanzapine/fluoxetine combination.
AB - BACKGROUND: We examined the efficacy of olanzapine/fluoxetine combination (OFC)
in improving health-related quality of life (QoL) in the treatment of bipolar
depression in children and adolescents. METHODS: Patients aged 10-17 years with
bipolar I disorder, depressed episode, baseline children's depression rating
scale-revised (CDRS-R) total score >=40, Young Mania Rating Scale (YMRS) total
score <=15, and YMRS-item 1 <= 2 were randomized to OFC (6/25-12/50 mg/day
olanzapine/fluoxetine; n = 170) or placebo (n = 85) for up to 8 weeks of double
blind treatment. Patients and parents completed the revised KINDL questionnaire
for measuring health-related QoL in children and adolescents (KINDL-R) at
baseline and endpoint. The mean change in CDRS-R total and item scores were used
to compare improvement in symptomatology in patients taking OFC and placebo.
Tests were 2-sided using a Type I error cutoff of 0.05, and no adjustments for
multiple comparisons were made. RESULTS: Baseline QoL as measured by the KINDL-R
was substantially impaired relative to published norms for a healthy school-based
sample. OFC-treated patients demonstrated an improvement over placebo at endpoint
with respect to mean change from baseline in the patient-rated KINDL-R Self
esteem subscale score (p = 0.028), and in the parent KINDL-R ratings of emotional
well-being (p = 0.020), Self-esteem (p = 0.030), and Family (p = 0.006). At
endpoint, OFC-treated patients still had a lower QoL compared to the normative
population. OFC showed significant improvement (p <= 0.05) versus placebo on the
CDRS-R total score and on 7 of the 17 CDRS-R items. CONCLUSIONS: Patients aged 10
17 years with an acute episode of bipolar depression and their parents reported
greater improvements (parents noticed improvements in more areas than did their
offspring) on some aspects of QoL when treated with OFC compared with placebo.
However, after 8 weeks of treatment, KINDL-R endpoint scores remained lower than
those of the, presumably healthy, control population. Clinical trial registration
information A Study for Assessing Treatment of Patients Ages 10-17 with Bipolar
Depression; http://www.clinicaltrials.gov; NCT00844857.
PMID- 28706564
TI - Vitamin C induces specific demethylation of H3K9me2 in mouse embryonic stem cells
via Kdm3a/b.
AB - BACKGROUND: Histone methylation patterns regulate gene expression and are highly
dynamic during development. The erasure of histone methylation is carried out by
histone demethylase enzymes. We had previously shown that vitamin C enhances the
activity of Tet enzymes in embryonic stem (ES) cells, leading to DNA
demethylation and activation of germline genes. RESULTS: We report here that
vitamin C induces a remarkably specific demethylation of histone H3 lysine 9
dimethylation (H3K9me2) in naive ES cells. Vitamin C treatment reduces global
levels of H3K9me2, but not other histone methylation marks analyzed, as measured
by western blot, immunofluorescence and mass spectrometry. Vitamin C leads to
widespread loss of H3K9me2 at large chromosomal domains as well as gene promoters
and repeat elements. Vitamin C-induced loss of H3K9me2 occurs rapidly within 24 h
and is reversible. Importantly, we found that the histone demethylases Kdm3a and
Kdm3b are required for vitamin C-induced demethylation of H3K9me2. Moreover, we
show that vitamin C-induced Kdm3a/b-mediated H3K9me2 demethylation and Tet
mediated DNA demethylation are independent processes at specific loci. Lastly, we
document Kdm3a/b are partially required for the upregulation of germline genes by
vitamin C. CONCLUSIONS: These results reveal a specific role for vitamin C in
histone demethylation in ES cells and document that DNA methylation and H3K9me2
cooperate to silence germline genes in pluripotent cells.
PMID- 28706565
TI - Once-daily glatiramer acetate decreases magnetic resonance imaging disease
activity in Japanese patients with relapsing-remitting multiple sclerosis.
AB - OBJECTIVE: Multiple sclerosis (MS) prevalence, clinical patterns, and treatment
responses vary between races and geographical latitudes. Glatiramer acetate (GA;
Copaxone) has provided a safe, effective treatment option for relapsing-remitting
MS patients in the USA, European nations, and other countries for decades. The
objective of the present study was to assess the safety and efficacy of GA in
reducing magnetic resonance imaging disease activity in Japanese patients with
active relapsing-remitting MS. METHODS: This phase 2, multicenter, open-label,
single-arm, 52-week study measured the effect of GA 20 mg once-daily on magnetic
resonance imaging disease activity. GA efficacy was evaluated through week 36,
and safety through week 52. The primary end-point was change in the mean number
of T1-weighted gadolinium-enhancing (GdE) lesions from pretreatment (weeks -8, -4
and baseline) to weeks 28, 32 and 36. Secondary end-points included a change in
mean number of new T2-weighted lesions, GdE lesion and T2 lesion volumes,
annualized relapse rate, and Expanded Disability Status Scale scores. RESULTS: GA
therapy reduced the number of new GdE lesions by 65.66% (95% CI 33.19-82.35%).
The number of new T2 lesions and GdE lesion volume were also reduced from
pretreatment. The annualized relapse rate was reduced by 42% compared with the 1
year before treatment. Changes in T2 lesion volume and Expanded Disability Status
Scale scores were favorable, but less pronounced. Most common adverse events were
injection-site reactions. CONCLUSIONS: The present study confirmed the well
established safety, tolerability and efficacy profile of GA in Japanese MS
patients.
PMID- 28706566
TI - Motor vehicle collisions caused by the 'super-strength' synthetic cannabinoids,
MAM-2201, 5F-PB-22, 5F-AB-PINACA, 5F-AMB and 5F-ADB in Japan experienced from
2012 to 2014.
AB - From 2012 to 2014 in Japan, 214 cases of motor vehicle collisions were attributed
to the use of illegal drugs. In 93 out of 96 investigated cases, the causative
agents were a variety of synthetic cannabinoids (SCs). These SCs can be
classified into three groups according to the lineage of the chemical structures:
(1) naphthoyl indoles, such as MAM-2201, (2) quinolinyl ester indoles, such as 5F
PB-22, and (3) indazole carboxamides, such as 5F-AB-PINACA, 5F-AMB, and 5F-ADB.
These SCs became available sequentially with increasing cannabinoid CB1 agonist
potencies and reached a nationwide outbreak in the summer of 2014. They caused
acute intoxication with impaired consciousness, anterograde amnesia (impaired
memory), catalepsy with muscle rigidity, tachycardia, and vomiting or drooling
soon after smoking. Drivers who had abused one of these SCs might unexpectedly
experience the acute intoxication that caused uncontrolled driving. These SCs
were generally difficult to detect from body fluid samples. It is thought that
the highly lipophilic SCs disappear from the blood via rapid degradation by liver
enzymes and selective accumulation into adipose tissues. Thus, much effort should
be directed to the development of fast and sensitive chemical detection of the
drug usage.
PMID- 28706567
TI - 25I-NBOH: a new potent serotonin 5-HT2A receptor agonist identified in blotter
paper seizures in Brazil.
AB - A new potent serotonin 5-HT2A receptor agonist was identified in blotter papers
by several state level forensic laboratories in Brazil. The 25I-NBOH is a labile
molecule, which fragments into 2C-I when analyzed by routine seized material
screening gas chromatography (GC) methods. GC-mass spectrometry (MS), liquid
chromatography-quadrupole time-of-flight-MS, and Fourier transform infrared and
nuclear magnetic resonance analyses were performed to complete molecular
characterization. Individual doses range from 300 to 1000 MUg. Despite its being
a potent 5-HT2A receptor agonist, 25I-NBOH is neither registered in the United
Nations Office on Drugs and Crime (UNODC) nor classified as a scheduled substance
in most countries. Sweden and Brazil seem to be the only countries to control 25I
NBOH. To our knowledge, this is the first scientific report dealing with
identification of 25I-NBOH in actual seizures.
PMID- 28706568
TI - Gold(I)-Mediated Thiourea Organocatalyst Activation: A Synergic Effect for
Asymmetric Catalysis.
AB - Several group 11 metal complexes with chiral thiourea organocatalysts have been
prepared and tested as organocatalysts. The promising results on the influence of
metal-assisted thiourea organocatalysts in the asymmetric Friedel-Crafts
alkylation of indole with nitrostyrene are described. Better results with the
metal complexes have been achieved because of the cooperative effects between the
chiral thiourea and the metal. The synergic effect between both species is higher
than the effect promoted by each one separately, especially for gold(I). These
outcomes are attributed to a pioneering gold(I) activation of the thiourea
catalysts, affording a more acidic and rigid catalytic complex than that provided
by the thiourea alone. Furthermore, the use of the gold-thiourea organocatalyst
allows reducing the catalyst loading to 1-3 mol %. This contribution could become
an important starting point for further investigations opening a new line of
research overlooked so far in the literature.
PMID- 28706569
TI - Supercritical Antisolvent Precipitation of Amorphous Copper-Zinc Georgeite and
Acetate Precursors for the Preparation of Ambient-Pressure Water-Gas-Shift
Copper/Zinc Oxide Catalysts.
AB - A series of copper-zinc acetate and zincian georgeite precursors have been
produced by supercritical CO2 antisolvent (SAS) precipitation as precursors to
Cu/ZnO catalysts for the water gas shift (WGS) reaction. The amorphous materials
were prepared by varying the water/ethanol volumetric ratio in the initial metal
acetate solutions. Water addition promoted georgeite formation at the expense of
mixed metal acetates, which are formed in the absence of the water co-solvent.
Optimum SAS precipitation occurs without water to give high surface areas,
whereas high water content gives inferior surface areas and copper-zinc
segregation. Calcination of the acetates is exothermic, producing a mixture of
metal oxides with high crystallinity. However, thermal decomposition of zincian
georgeite resulted in highly dispersed CuO and ZnO crystallites with poor
structural order. The georgeite-derived catalysts give superior WGS performance
to the acetate-derived catalysts, which is attributed to enhanced copper-zinc
interactions that originate from the precursor.
PMID- 28706570
TI - The Effects of Secondary Oxides on Copper-Based Catalysts for Green Methanol
Synthesis.
AB - Catalysts for methanol synthesis from CO2 and H2 have been produced by two main
methods: co-precipitation and supercritical anti-solvent (SAS) precipitation.
These two methods are compared, along with the behaviour of copper supported on
Zn, Mg, Mn, and Ce oxides. Although the SAS method produces initially active
material with high Cu specific surface area, they appear to be unstable during
reaction losing significant amounts of surface area and hence activity. The CuZn
catalysts prepared by co-precipitation, however, showed much greater thermal and
reactive stability than the other materials. There appeared to be the usual near
linear dependence of activity upon Cu specific area, though the initial
performance relationship was different from that post-reaction, after some loss
of surface area. The formation of the malachite precursor, as reported before, is
important for good activity and stability, whereas if copper oxides are formed
during the synthesis and ageing process, then a detrimental effect on these
properties is seen.
PMID- 28706571
TI - Is Addiction a Brain Disease?
AB - Where does normal brain or psychological function end, and pathology begin? The
line can be hard to discern, making disease sometimes a tricky word. In
addiction, normal 'wanting' processes become distorted and excessive, according
to the incentive-sensitization theory. Excessive 'wanting' results from drug
induced neural sensitization changes in underlying brain mesolimbic systems of
incentive. 'Brain disease' was never used by the theory, but neural sensitization
changes are arguably extreme enough and problematic enough to be called
pathological. This implies that 'brain disease' can be a legitimate description
of addiction, though caveats are needed to acknowledge roles for choice and
active agency by the addict. Finally, arguments over 'brain disease' should be
put behind us. Our real challenge is to understand addiction and devise better
ways to help. Arguments over descriptive words only distract from that challenge.
PMID- 28706572
TI - A Microwell-Printing Fabrication Strategy for the On-Chip Templated Biosynthesis
of Protein Microarrays for Surface Plasmon Resonance Imaging.
AB - A two-step templated, ribosomal biosynthesis/printing method for the fabrication
of protein microarrays for surface plasmon resonance imaging (SPRI) measurements
is demonstrated. In the first step, a sixteen component microarray of proteins is
created in microwells by cell free on chip protein synthesis; each microwell
contains both an in vitro transcription and translation (IVTT) solution and 350
femtomoles of a specific DNA template sequence that together are used to create
approximately 40 picomoles of a specific hexahistidine-tagged protein. In the
second step, the protein microwell array is used to contact print one or more
protein microarrays onto nitrilotriacetic acid (NTA)-functionalized gold thin
film SPRI chips for real-time SPRI surface bioaffinity adsorption measurements.
Even though each microwell array element only contains approximately 40 picomoles
of protein, the concentration is sufficiently high for the efficient bioaffinity
adsorption and capture of the approximately 100 femtomoles of hexahistidine
tagged protein required to create each SPRI microarray element. As a first
example, the protein biosynthesis process is verified with fluorescence imaging
measurements of a microwell array containing His-tagged green fluorescent protein
(GFP), yellow fluorescent protein (YFP) and mCherry (RFP), and then the fidelity
of SPRI chips printed from this protein microwell array is ascertained by
measuring the real-time adsorption of various antibodies specific to these three
structurally related proteins. This greatly simplified two-step
synthesis/printing fabrication methodology eliminates most of the handling,
purification and processing steps normally required in the synthesis of multiple
protein probes, and enables the rapid fabrication of SPRI protein microarrays
from DNA templates for the study of protein-protein bioaffinity interactions.
PMID- 28706573
TI - The effects of catchment and riparian forest quality on stream environmental
conditions across a tropical rainforest and oil palm landscape in Malaysian
Borneo.
AB - Freshwaters provide valuable habitat and important ecosystem services but are
threatened worldwide by habitat loss and degradation. In Southeast Asia,
rainforest streams are particularly threatened by logging and conversion to oil
palm, but we lack information on the impacts of this on freshwater environmental
conditions, and the relative importance of catchment versus riparian-scale
disturbance. We studied 16 streams in Sabah, Borneo, including old-growth forest,
logged forest, and oil palm sites. We assessed forest quality in riparian zones
and across the whole catchment and compared it with stream environmental
conditions including water quality, structural complexity, and organic inputs. We
found that streams with the highest riparian forest quality were nearly 4
degrees C cooler, over 20 cm deeper, had over 40% less sand, greater canopy
cover, more stored leaf litter, and wider channels than oil palm streams with the
lowest riparian forest quality. Other variables were significantly related to
catchment-scale forest quality, with streams in the highest quality forest
catchments having 40% more bedrock and 20 times more dead wood, along with higher
phosphorus, and lower nitrate-N levels compared to streams with the lowest
catchment-scale forest quality. Although riparian buffer strips went some way to
protecting waterways, they did not maintain fully forest-like stream conditions.
In addition, logged forest streams still showed signs of disturbance 10-15 years
after selective logging. Our results suggest that maintenance and restoration of
buffer strips can help to protect healthy freshwater ecosystems but logging
practices and catchment-scale forest management also need to be considered.
PMID- 28706574
TI - Neuronal Damage Induced by Perinatal Asphyxia Is Attenuated by Postinjury
Glutaredoxin-2 Administration.
AB - The general disruption of redox signaling following an ischemia-reperfusion
episode has been proposed as a crucial component in neuronal death and
consequently brain damage. Thioredoxin (Trx) family proteins control redox
reactions and ensure protein regulation via specific, oxidative posttranslational
modifications as part of cellular signaling processes. Trx proteins function in
the manifestation, progression, and recovery following hypoxic/ischemic damage.
Here, we analyzed the neuroprotective effects of postinjury, exogenous
administration of Grx2 and Trx1 in a neonatal hypoxia/ischemia model. P7 Sprague
Dawley rats were subjected to right common carotid ligation or sham surgery,
followed by an exposure to nitrogen. 1 h later, animals were injected i.p. with
saline solution, 10 mg/kg recombinant Grx2 or Trx1, and euthanized 72 h
postinjury. Results showed that Grx2 administration, and to some extent Trx1,
attenuated part of the neuronal damage associated with a perinatal
hypoxic/ischemic damage, such as glutamate excitotoxicity, axonal integrity, and
astrogliosis. Moreover, these treatments also prevented some of the consequences
of the induced neural injury, such as the delay of neurobehavioral development.
To our knowledge, this is the first study demonstrating neuroprotective effects
of recombinant Trx proteins on the outcome of neonatal hypoxia/ischemia, implying
clinical potential as neuroprotective agents that might counteract neonatal
hypoxia/ischemia injury.
PMID- 28706576
TI - Adherence to the Mediterranean Diet and Circulating Levels of Sirtuin 4 in Obese
Patients: A Novel Association.
AB - PURPOSE: This study was aimed at evaluating sirtuin 4 (Sirt4) levels in obese
individuals, in relation to their adherence to the Mediterranean diet (MD), a
healthy dietary pattern characterized by high antioxidant capacity, and markers
of visceral fat storage. SUBJECTS/METHODS: Forty-three obese patients (44% males;
BMI: 36.7-58.8 kg/m2) were consecutively included. PREvencion con DIeta
MEDiterranea (PREDIMED) and the 7-day food records were used to assess the
adherence to MD and dietary pattern, respectively. Visceral adiposity index (VAI)
was calculated. Sirt4 levels were detected by ELISA method. RESULTS: The majority
of the obese participants (62.8%) had an average adherence to MD. Compared with
average adherers, low adherers had higher BMI, energy intake, and percentage of
energy from lipids, mainly saturated fat and polyunsaturated fatty acids (PUFA),
and lower Sirt4 levels. After adjusting for BMI, Sirt4 levels remained negatively
correlated with VAI. After adjusting for total energy intake, Sirt4 levels
remained negatively associated with PREDIMED and consumption of n-3 PUFA,
vitamins C and E. The threshold value of PREDIMED predicting the lowest decrease
in Sirt4 levels was found at a score of 6. CONCLUSIONS: Less reduced Sirt4 levels
in obese patients adhering to MD suggest a further aspect of the antioxidant
advantage of MD.
PMID- 28706575
TI - Targeting Endothelial Function to Treat Heart Failure with Preserved Ejection
Fraction: The Promise of Exercise Training.
AB - Although the burden of heart failure with preserved ejection fraction (HFpEF) is
increasing, there is no therapy available that improves prognosis. Clinical
trials using beta blockers and angiotensin converting enzyme inhibitors, cardiac
targeting drugs that reduce mortality in heart failure with reduced ejection
fraction (HFrEF), have had disappointing results in HFpEF patients. A new "whole
systems" approach has been proposed for designing future HFpEF therapies, moving
focus from the cardiomyocyte to the endothelium. Indeed, dysfunction of
endothelial cells throughout the entire cardiovascular system is suggested as a
central mechanism in HFpEF pathophysiology. The objective of this review is to
provide an overview of current knowledge regarding endothelial dysfunction in
HFpEF. We discuss the molecular and cellular mechanisms leading to endothelial
dysfunction and the extent, presence, and prognostic importance of clinical
endothelial dysfunction in different vascular beds. We also consider implications
towards exercise training, a promising therapy targeting system-wide endothelial
dysfunction in HFpEF.
PMID- 28706577
TI - Risperidone-Induced Renal Damage and Metabolic Side Effects: The Protective
Effect of Resveratrol.
AB - OBJECTIVE: The aim of the study was to investigate the possible protective
qualities of resveratrol (RSV) against the side effects of risperidone (RIS) in
an experimental model in rat kidneys with histologic and biochemical assessments.
MATERIALS AND METHODS: Experimental procedures were performed on 35 female
Sprague Dawley rats. Rats were randomly divided into five groups: control,
untreated rats (n = 7) were in group 1; group 2 was given 2 mg/kg/day RIS (n =
7); group 3 was treated with 2 mg/kg/day RIS and 20 mg/kg/day RSV (n = 7); group
4 was treated with 2 mg/kg/day RIS and 40 mg/kg/day RSV (n = 7); and group 5 was
treated with 2 mg/kg/day RIS and 80 mg/kg/day RSV (n = 7). All treatments were
administered for two weeks by gavage. On treatment day 15, kidney tissues were
removed for analysis. RESULTS: The results showed that RSV treatment reduced
weight gain induced by RIS. In addition, RSV increased the total antioxidant
status (TAS) and decreased serum creatinine (Cr), blood urea nitrogen (BUN),
oxidative stress index (OSI), and total oxidant status (TOS) levels significantly
(p < 0.05). CONCLUSION: This study revealed that treatment with RSV might protect
kidney tissues against the side effects of RIS. RSV could be an effective course
of therapy to enhance therapeutic efficacy.
PMID- 28706579
TI - Conventional vs drug-eluting beads transarterial chemoembolization for
hepatocellular carcinoma.
AB - Transarterial chemoembolization (TACE) is the current standard of therapy for
patients with intermediate-stage hepatocellular carcinoma (HCC) according to the
Barcelona Clinic Liver Cancer classification. The concept of conventional TACE
(cTACE) is the selective obstruction of tumor-feeding artery by injection of
chemotherapeutic agents, leading to ischemic necrosis of the target tumor via
cytotoxic and ischemic effects. Drug-eluting beads (DEBs) have been imposed as
novel drug-delivering agents for TACE, which allows for higher concentrations of
drugs within the target tumor and lower systemic concentrations compared with
cTACE. Despite the theoretical advantages of DEB-TACE, it is still controversial
in clinical practice as to whether DEB-TACE is superior to cTACE in regard to
overall survival and treatment response. In this review article, we summarize the
clinical efficacy and safety of DEB-TACE for patients with intermediate or
advanced stage HCC in comparison with cTACE.
PMID- 28706578
TI - Systemic treatment of hepatocellular carcinoma: Past, present and future.
AB - Hepatocellular carcinoma (HCC) is a common neoplasia which represents the second
leading cause of cancer related death. Most cases occur in developing countries,
but its incidence is rising in Western countries due to hepatitis C. Although
hepatitis therapies have evolved and the HCC screening has increased in several
areas, 40% present with advanced disease which is only amenable for palliative
systemic treatment. HCC continues posing a challenge, in part due to the inherent
chemoresistance of this neoplasia, the pharmacologic challenges due to an ill
liver, difficulty in assessing radiological responses accurately, etc.
Traditional chemotherapy have shown some responses without clear survival
benefit, however, sorafenib demonstrated advantages in survival in advanced HCC
when liver function is kept and recently immunotherapy seems to be a promising
approach for some patients. This article will briefly expose the most relevant
systemic treatment modalities to offer a general view from the past to the
future.
PMID- 28706580
TI - Risk factors for acute kidney injury after partial hepatectomy.
AB - AIM: To identify risk factors for the occurrence of acute kidney injury (AKI) in
the postoperative period of partial hepatectomies. METHODS: Retrospective
analysis of 446 consecutive resections in 405 patients, analyzing clinical
characteristics, preoperative laboratory data, intraoperative data, and
postoperative laboratory data and clinical evolution. Adopting the International
Club of Ascites criteria for the definition of AKI, potential predictors of AKI
by logistic regression were identified. RESULTS: Of the total 446 partial liver
resections, postoperative AKI occurred in 80 cases (17.9%). Identified predictors
of AKI were: Non-dialytic chronic kidney injury (CKI), biliary obstruction, the
Model for End-Stage Liver Disease (MELD) score, the extent of hepatic resection,
the occurrence of intraoperative hemodynamic instability, post-hepatectomy
haemorrhage, and postoperative sepsis. CONCLUSION: The MELD score, the presence
of non-dialytic CKI and biliary obstruction in the preoperative period, and
perioperative hemodynamics instability, bleeding, and sepsis are risk factors for
the occurrence of AKI in patients that underwent partial hepatectomy.
PMID- 28706581
TI - Early acute kidney injury after liver transplantation: Predisposing factors and
clinical implications.
AB - AIM: To investigate the additional clinical impact of hepatic ischaemia
reperfusion injury (HIRI) on patients sustaining acute kidney injury (AKI)
following liver transplantation. METHODS: This was a single-centre retrospective
study of consecutive adult patients undergoing orthotopic liver transplantation
(OLT) between January 2013 and June 2014. Early AKI was identified by measuring
serum creatinine at 24 h post OLT (> 1.5 * baseline) or by the use of continuous
veno-venous haemofiltration (CVVHF) during the early post-operative period.
Patients with and without AKI were compared to identify risk factors associated
with this complication. Peak serum aspartate aminotransferase (AST) within 24 h
post-OLT was used as a surrogate marker for HIRI and severity was classified as
minor (< 1000 IU/L), moderate (1000-5000 IU/L) or severe (> 5000 IU/L). The
impact on time to extubation, intensive care length of stay, incidence of chronic
renal failure and 90-d mortality were examined firstly for each of the two
complications (AKI and HIRI) alone and then as a combined outcome. RESULTS: Out
of the 116 patients included in the study, 50% developed AKI, 24% required CVVHF
and 70% sustained moderate or severe HIRI. Median peak AST levels were 1248 IU/L
and 2059 IU/L in the No AKI and AKI groups respectively (P = 0.0003).
Furthermore, peak serum AST was the only consistent predictor of AKI on
multivariate analysis P = 0.02. AKI and HIRI were individually associated with a
longer time to extubation, increased length of intensive care unit stay and
reduced survival. However, the patients who sustained both AKI and moderate or
severe HIRI had a longer median time to extubation (P < 0.001) and intensive care
length of stay (P = 0.001) than those with either complication alone. Ninety-day
survival in the group sustaining both AKI and moderate or severe HIRI was 89%,
compared to 100% in the groups with either or neither complication (P = 0.049).
CONCLUSION: HIRI has an important role in the development of AKI post-OLT and has
a negative impact on patient outcomes, especially when occurring alongside AKI.
PMID- 28706582
TI - A Bayesian Adaptive Design for Combination of Three Drugs in Cancer Phase I
Clinical Trials.
AB - We describe a Bayesian adaptive design for early phase cancer trials of a
combination of three agents. This is an extension of an earlier work by the
authors by allowing all three agents to vary during the trial and by assigning
different drug combinations to cohorts of three patients. The primary objective
is to estimate the Maximum Tolerated Dose (MTD) surface in the three-dimensional
Cartesian space. A class of linear models on the logit of the probability of Dose
Limiting Toxicity (DLT) are used to describe the relationship between doses of
the three drugs and the probability of DLT. Trial design proceeds using
conditional escalation with overdose control, where at each stage of the trial,
we seek a dose of one agent using the current posterior distribution of the MTD
of this agent given the current doses of the other two agents. The MTD surface is
estimated at the end of the trial as a function of Bayes estimates of the model
parameters. Operating characteristics are evaluated with respect to trial safety
and percent of dose recommendation at dose combination neighborhoods around the
true MTD surface.
PMID- 28706583
TI - Cardiac damage in athlete's heart: When the "supernormal" heart fails!
AB - Intense exercise may cause heart remodeling to compensate increases in blood
pressure or volume by increasing muscle mass. Cardiac changes do not involve only
the left ventricle, but all heart chambers. Physiological cardiac modeling in
athletes is associated with normal or enhanced cardiac function, but recent
studies have documented decrements in left ventricular function during intense
exercise and the release of cardiac markers of necrosis in athlete's blood of
uncertain significance. Furthermore, cardiac remodeling may predispose athletes
to heart disease and result in electrical remodeling, responsible for
arrhythmias. Athlete's heart is a physiological condition and does not require a
specific treatment. In some conditions, it is important to differentiate the
physiological adaptations from pathological conditions, such as hypertrophic
cardiomyopathy, arrhythmogenic dysplasia of the right ventricle, and non
compaction myocardium, for the greater risk of sudden cardiac death of these
conditions. Moreover, some drugs and performance-enhancing drugs can cause
structural alterations and arrhythmias, therefore, their use should be excluded.
PMID- 28706584
TI - Assessment of aortic valve disease - a clinician oriented review.
AB - Aortic valve disease [aortic stenosis (AS) and aortic regurgitation (AR)]
represents an important global health problem; when severe, aortic valve disease
carries poor prognosis. For AS, aortic valve replacement, either surgical or
interventional, may provide definite treatment in carefully selected patients.
For AR, valve surgery (either replacement or - in selected cases - aortic valve
repair) remains the gold standard of care. To properly identify those patients
who are candidates for surgery, the clinician has to carefully assess the
severity of valve disease with an understanding of the potential pitfalls
involved in these assessments. This review focuses on the practical issues
concerning the evaluation of patients with AS and AR from a general
cardiologist's perspective. The most important issues regarding the documentation
of the severity of AS and AR are summarized. More specific issues, such as the
role of stress echocardiography, other imaging techniques and details regarding
the treatment options (medical, surgical, or interventional), are mentioned
briefly.
PMID- 28706585
TI - Atrial tachyarrhythmia in adult congenital heart disease.
AB - The adult congenital heart disease (ACHD) population continues to grow and most
cardiologists, emergency room physicians and family doctors will intermittently
come into contact with these patients. Oftentimes this may be in the setting of a
presentation with atrial tachyarrhythmia; one of the commonest late complications
of ACHD and problem with potentially serious implications. Providing appropriate
initial care and ongoing management of atrial tachyarrhythmia in ACHD patients
requires a degree of specialist knowledge and an awareness of certain key issues.
In ACHD, atrial tachyarrhythmia is usually related to the abnormal anatomy of the
underlying heart defect and often occurs as a result of surgical scar or a
consequence of residual hemodynamic or electrical disturbances. Arrhythmias
significantly increase mortality and morbidity in ACHD and are the most frequent
reason for ACHD hospitalization. Intra-atrial reentrant tachycardia and atrial
fibrillation are the most prevalent type of arrhythmia in this patient group. In
hemodynamically unstable patients, urgent cardioversion is required. Acute
management of the stable patient includes anticoagulation, rate control, and
electrical or pharmacological cardioversion. In ACHD, rhythm control is the
preferred management strategy and can often be achieved. However, in the long
term, medication side-effects can prove problematic. Electrophysiology studies
and catheter ablation are important treatments modalities and in certain cases,
surgical or percutaneous treatment of the underlying cardiac defect has a role.
ACHD patients, especially those with complex CHD, are at increased risk of
thromboembolic events and anticoagulation is usually required. Female ACHD
patients of child bearing age may wish to pursue pregnancies. The risk of atrial
arrhythmias is increased during pregnancy and management of atrial
tachyarrhythmia during pregnancy needs specific consideration.
PMID- 28706586
TI - Influence of cardiac nerve status on cardiovascular regulation and
cardioprotection.
AB - Neural elements of the intrinsic cardiac nervous system transduce sensory inputs
from the heart, blood vessels and other organs to ensure adequate cardiac
function on a beat-to-beat basis. This inter-organ crosstalk is critical for
normal function of the heart and other organs; derangements within the nervous
system hierarchy contribute to pathogenesis of organ dysfunction. The role of
intact cardiac nerves in development of, as well as protection against, ischemic
injury is of current interest since it may involve recruitment of intrinsic
cardiac ganglia. For instance, ischemic conditioning, a novel protection strategy
against organ injury, and in particular remote conditioning, is likely mediated
by activation of neural pathways or by endogenous cytoprotective blood-borne
substances that stimulate different signalling pathways. This discovery
reinforces the concept that inter-organ communication, and maintenance thereof,
is key. As such, greater understanding of mechanisms and elucidation of treatment
strategies is imperative to improve clinical outcomes particularly in patients
with comorbidities. For instance, autonomic imbalance between sympathetic and
parasympathetic nervous system regulation can initiate cardiovascular autonomic
neuropathy that compromises cardiac stability and function. Neuromodulation
therapies that directly target the intrinsic cardiac nervous system or other
elements of the nervous system hierarchy are currently being investigated for
treatment of different maladies in animal and human studies.
PMID- 28706587
TI - Management of ventricular tachycardia storm in patients with structural heart
disease.
AB - Electrical storm (ES) is a medical emergency characterized by repetitive episodes
of sustained ventricular arrhythmias (VAs) in a limited amount of time (at least
3 within a 24-h period) leading to repeated appropriate implantable cardioverter
defibrillator therapies. The occurrence of ES represents a major turning point in
the natural history of patients with structural heart disease being associated
with poor short- and long-term survival particularly in those with compromised
left ventricular ejection fraction (LVEF) that can develop hemodynamic
decompensation and multi-organ failure. Management of ES is challenging with
limited available evidence coming from small retrospective series and a
substantial lack of randomized-controlled trials. In general, a multidisciplinary
approach including medical therapies such as anti-arrhythmic drugs, sedation, as
well as interventional approaches like catheter ablation, may be required.
Accurate patient risk stratification at admission for ES is pivotal and should
take into account hemodynamic tolerability of VAs as well as comorbidities like
low LVEF, advanced NYHA class and chronic pulmonary disease. In high risk
patients, prophylactic mechanical circulatory support with left ventricular
assistance devices or extracorporeal membrane oxygenation should be considered as
bridge to ablation and recovery. In the present manuscript we review the
available strategies for management of ES and the evidence supporting them.
PMID- 28706588
TI - Wearable cardioverter defibrillator: Bridge or alternative to implantation?
AB - The implantable cardioverter-defibrillator (ICD) is effective to prevent sudden
cardiac death (SCD) in selected patients with heart disease known to be at high
risk for ventricular arrhythmia. Nevertheless, this invasive and definitive
therapy is not indicated in patients with potentially transient or reversible
causes of sudden death, or in patients with temporary contra-indication for ICD
placement. The wearable cardioverter defibrillator (WCD) is increasingly used for
SCD prevention both in patients awaiting ICD implantation or with an estimated
high risk of ventricular arrhythmia though to be transient. We conducted a review
of current clinical uses and benefits of the WCD, and described its technical
aspects, limitations and perspectives.
PMID- 28706589
TI - Catheter ablation of atrial fibrillation facilitated by preprocedural three
dimensional transesophageal echocardiography: Long-term outcome.
AB - AIM: To evaluate the long-term outcome of catheter ablation of atrial
fibrillation (AF) facilitated by preprocedural three-dimensional (3-D)
transesophageal echocardiography. METHODS: In 50 patients, 3D transesophageal
echocardiography (3D TEE) was performed immediately prior to an ablation
procedure (paroxysmal AF: 30 patients, persistent AF: 20 patients). The images
were available throughout the ablation procedure. Two different ablation
strategies were used. In most of the patients with paroxysmal AF, the
cryoablation technique was used (Arctic Front Balloon, CryoCath
Technologies/Medtronic; group A2). In the other patients, a circumferential
pulmonary vein ablation was performed using the CARTO system [Biosense Webster;
group A1 (paroxysmal AF), group B (persistent AF)]. Success rates and
complication rates were analysed at 4-year follow-up. RESULTS: A 3D TEE could be
performed successfully in all patients prior to the ablation procedure and all
four pulmonary vein ostia could be evaluated in 84% of patients. The image
quality was excellent in the majority of patients and several variations of the
pulmonary vein anatomy could be visualized precisely (e.g., common pulmonary vein
ostia, accessory pulmonary veins, varying diameter of the left atrial appendage
and its distance to the left superior pulmonary vein). All ablation procedures
could be performed as planned and almost all pulmonary veins could be isolated
successfully. At 48-mo follow-up, 68.0% of all patients were free from an
arrhythmia recurrence (group A1: 72.7%, group A2: 73.7%, group B: 60.0%). There
were no major complications. CONCLUSION: 3D TEE provides an excellent overview
over the left atrial anatomy prior to AF ablation procedures and these procedures
are associated with a favourable long-term outcome.
PMID- 28706590
TI - Entirely subcutaneous defibrillator and complex congenital heart disease: Data on
long-term clinical follow-up.
AB - AIM: To describe the long-term follow-up of patients with complex congenital
heart disease who underwent subcutaneous implantable cardiac defibrillator (S
ICD), focusing on local complications, appropriate and inappropriate shocks.
METHODS: Patients with complex congenital heart disease underwent S-ICD implant
in two centers with the conventional technique. Data at follow-up were retrieved
from clinical notes and institutional database. RESULTS: Eight patients were
implanted in two centres between 2010 and 2016. Median age at implant was 37.5
years (range 13-57). All patients who were deemed suitable for S-ICD implant
passed the pre-procedural screening. Three patients were previously implanted
with a anti-bradycardia device, one of whom with CRT. In one patient the device
was explanted due to local infection. During the total median follow-up of 874 d,
one patient had an appropriate and one inappropriate shock triggered by fast
atrial tachycardia. None of the patients had inappropriate shocks secondary to T
wave oversensing or electrical interference with anti- bradycardia devices.
CONCLUSION: S-ICD appears to be effective and safe in patients with complex
congenital heart disease.
PMID- 28706591
TI - Interferon related pericarditis: Review.
AB - AIM: To conduct a review of "interferon related pericarditis". METHODS: We
searched MEDLINE, EMBASE, Cinahl, and the Cochrane Database from the earliest
available date through September 2016. A search strategy using the Medical
Subject Headings and text keywords "interferon" and "pericarditis" were used.
RESULTS: Nine case reports were eligible for the present study. Six of 8 cases
were women and the mean age was 43.8 +/- 13.8 years with chronic hepatitis C in 6
cases, malignant melanoma in 2 cases and chronic myelogenous leukemia in 1 case.
The patients complained of chest pain in 6 cases, dyspnea in 5 cases and edema in
2 cases. Pericardial friction rub was heard in 3 of 9 cases. Congestive heart
failure occurred in 3 of 9 cases. Two mechanisms for pericarditis were
demonstrated, one is autoimmune included lupus like syndrome in 2 cases and the
other is cardio toxicity in 4 cases. Treatment of interferon related pericarditis
is discontinuation of Interferon treatment. Four of 9 cases were treated with
prednisone and 4 with nonsteroidal anti-inflammatory drugs. CONCLUSION:
Interferon related pericarditis still remains uncertain. Treatment of interferon
related pericarditis rests mainly on early recognition and drug discontinuation.
Interferon related pericarditis was treated with steroid and/or nonsteroidal anti
inflammatory drugs.
PMID- 28706592
TI - Inadvertent cardiac phlebography.
AB - We are reporting a case of a 80-year-old lady with effort angina who underwent
coronary angiography through the right radial artery, using a dedicated radial
multipurpose 5 French Optitorque Tiger catheter. The catheter was advanced into
the left ventricle and a left ventriculogram was obtained, while the catheter
appeared optimally placed at the centre of the ventricle and the pressure
waveform was normal. A large posterior interventricular vein draining into the
right atrium was opacified, presumably because the catheter's end hole
inadvertently cannulated an endocardial opening of a small thebesian vein, with
subsequent retrograde filling of the epicardial vein. Our case suggests that
caution is needed when a dedicated radial catheter with both an end-hole and a
side hole is used for a ventriculogram, as a normal left ventricular pressure
waveform does not exclude malposition of the end-hole against the ventricular
wall.
PMID- 28706593
TI - Estimates of linkage disequilibrium and effective population sizes in Chinese
Merino (Xinjiang type) sheep by genome-wide SNPs.
AB - Knowledge of linkage disequilibrium (LD) is important for effective genome-wide
association studies and accurate genomic prediction. Chinese Merino (Xinjiang
type) is well-known fine wool sheep breed. However, the extent of LD across the
genome remains unexplored. In this study, we calculated autosomal LD based on
genome-wide SNPs of 635 Chinese Merino (Xinjiang type) sheep by Illumina Ovine
SNP50 BeadChip. A moderate level of LD (r2 >= 0.25) across the whole genome was
observed at short distances of 0-10 kb. Further, the ancestral effective
population size (Ne ) was analyzed by extent of LD and found that Ne increased
with the increase of generations and declined rapidly within the most recent 50
generations, which is consistent with the history of Chinese Merino sheep
breeding, initiated in 1971. We also noted that even when the effective
population size was estimated across different single chromosomes, Ne only ranged
from 140.36 to 183.33 at five generations in the past, exhibiting a rapid
decrease compared with that at ten generations in the past. These results
indicated that the genetic diversity in Chinese Merino sheep recently decreased
and proper protective measures should be taken to maintain the diversity. Our
datasets provided essential genetic information to track molecular variations
which potentially contribute to phenotypic variation in Chinese Merino sheep.
PMID- 28706594
TI - Disparity in ST-segment Elevation Myocardial Infarction Practices and Outcomes in
Arabian Gulf Countries (Gulf COAST Registry).
AB - OBJECTIVES: The objective of this study is to describe contemporary management
and 1-year outcomes of patients hospitalized with ST-segment elevation myocardial
infarction (STEMI) in Arabian Gulf countries. METHODS: Data of patients admitted
to 29 hospitals in four Gulf countries [Bahrain, Kuwait, Oman, United Arab
Emirates (UAE)] with the diagnosis of STEMI were analyzed from Gulf locals with
acute coronary syndrome (ACS) events (Gulf COAST) registry. This was a
longitudinal, observational registry of consecutive citizens, admitted with ACS
from January 2012 to January 2013. Patient management and outcomes were analyzed
and compared between the four countries. RESULTS: A total of 1039 STEMI patients
were enrolled in Gulf COAST Registry. The mean age was 58 years, and there was a
high prevalence of diabetes (47%). With respect to reperfusion, 10% were
reperfused with primary percutaneous coronary intervention, 66% with fibrinolytic
therapy and 24% were not reperfused. Only one-third of patients who received
fibrinolytic therapy had a door-to-needle time of 30 min or less. The in-hospital
mortality rate was 7.4%. However, we noted a significant regional variability in
mortality rate (3.8%-11.9%). In adjusted analysis, patients from Oman were 4
times more likely to die in hospital as compared to patients from Kuwait.
CONCLUSIONS: In the Gulf countries, fibrinolytic therapy is the main reperfusion
strategy used in STEMI patients. Most patients do not receive this therapy
according to timelines outlined in recent practice guidelines. There is a
significant discrepancy in outcomes between the countries. Quality improvement
initiatives are needed to achieve better adherence to management guidelines and
close the gap in outcomes.
PMID- 28706595
TI - Pseudo-lesions of a Tortuous Right Coronary Artery During Percutaneous Coronary
Intervention: Accordion Phenomena.
AB - Guidewire-induced pseudo-lesions are referred to accordion phenomenon and are
infrequent occurrences during percutaneous coronary intervention of tortuous
coronary arteries. Their occurrence can be a diagnostic challenge to the
interventionist and might lead to unnecessary intervention. Ischemia and
hemodynamic compromise are possible complications, if not managed promptly. The
differential diagnosis includes coronary dissection, thrombus, and spasm. We
describe a patient who developed pseudo-lesions of the tortuous right coronary
artery in multiple segments during PCI. The pseudo-lesions were refractory to
intracoronary nitrogycerin.
PMID- 28706596
TI - Percutaneous Retrieval of a Knotted Provisional Pacemaker Using Proximal
Electrode Cut off and Distal End Snaring.
AB - Although provisional pacemaker implantation can safely be done in many cases, a
rare complication such as knotted electrode has been described, especially when
the procedure is performed without fluoroscopy guidance. We describe a case of
knot creation in a provisional pacemaker which was successfully retrieved using a
snare after cutting the electrode proximally.
PMID- 28706597
TI - An Infrequent Cause of Apical Ventricular Aneurysm in the United States.
AB - Chronic Chagas cardiomyopathy (CCC) is a late complication of Chagas disease with
various manifestations including arrhythmia, heart failure, thromboembolism, and
stroke. In a patient with symptoms of heart failure and left ventricular apical
aneurysm unexplained by structural heart or coronary vascular abnormalities, CCC
should be strongly considered and inquiry made about exposure status. Typical
electrocardiographic findings of bundle branch block, complete heart blocks, and
ventricular arrhythmia are helpful clues. A positive trypanosomal immunoglobulin
G antibody is supportive. Initiation of stage appropriate guideline-recommended
heart failure regimen is the goal with careful attention paid to prevention of
sudden cardiac death from ventricular arrhythmias.
PMID- 28706598
TI - A Fractional Flow Reserve Guidewire Causing Longitudinal Stent Compression and
Successful Recovery.
AB - Longitudinal stent deformation (LSD) is a rare complication but can occur during
coronary intervention. We report a case with LSD of the distal edge, documented
by an optical coherence tomography investigation and successfully recovered.
PMID- 28706599
TI - Acute Fulminant Uremic Neuropathy Following Coronary Angiography Mimicking
Guillain-Barre Syndrome.
AB - A 55-year-old diabetic woman suffered a posterior wall ST-elevation myocardial
infarction. She developed contrast-induced nephropathy following coronary
angiography. Acute fulminant uremic neuropathy was precipitated which initially
mimicked Guillan-Barre Syndrome, hence reported.
PMID- 28706600
TI - Dissecting Aneurysm of Aortic Root with Severe Aortic Regurgitation.
PMID- 28706601
TI - Despair and Hope.
PMID- 28706602
TI - Coronary Heart Disease: From Mummies to 21st Century.
PMID- 28706603
TI - Proximal Flow Control with a Balloon during the Treatment of Left Subclavian
Artery Aneurysms.
PMID- 28706604
TI - Innovation and Technology in Iran.
PMID- 28706605
TI - Embryonic Stem Cell Conditioned Medium Supports In Vitro Maturation of Mouse
Oocytes.
AB - BACKGROUND: This study aimed to investigate the maturation and fertilization
rates of immature mouse oocytes using Embryonic Stem Cell Conditioned Medium
(ESCM). METHODS: Germinal Vesicle (GV) stage oocytes were observed in 120 NMRI
mice, aged 4-6 weeks. GV oocytes with or without cumulus cells were subjected to
IVM in either ESCM, Embryonic Stem Cell Growth Medium (ESGM), or alpha-minimum
essential medium (alpha-MEM). After recording the Metaphase II (MII) oocyte
maturation rate, the oocytes were fertilized in vitro. The fertilization success
rate was recorded after 24 hr. The embryos were maintained in potassium Simplex
Optimization Medium (KSOM) for 96 hr and allowed to grow until the blastocyst
stage. After recording developmental competence, they were transferred into the
uteri of pseudopregnant mice and their birth rates were recorded. RESULTS: No
significant difference existed between the maturation rates in alpha-MEM (68.18%)
and ESCM (64.67%; p>0.05), whereas this rate was significantly higher for both
alpha-MEM and ESCM compared to ESGM (32.22%; p<0.05). A significant difference in
IVF success rate existed for oocytes grown in alpha-MEM (69.44%), ESCM (61.53%),
and ESGM (0%). A significantly higher developmental competence was observed at
the blastocyst stage for oocytes grown in alpha-MEM (51.2%) compared to ESCM
(35%; p<0.05). 17 days after embryo transfer into the uteri of pseudopregnant
mice, there was a nonsignficant (p>0.05), similar birth rate between alpha-MEM
and ESCM (47 vs. 40%). CONCLUSION: ESCM is an effective medium for preantral
follicle growth, oocyte maturation, and subsequent embryo development.
PMID- 28706606
TI - Biosynthesis of Silver Nanoparticles using Chlorella vulgaris and Evaluation of
the Antibacterial Efficacy Against Staphylococcus aureus.
AB - BACKGROUND: It is well documented that Silver Nanoparticles (SNPs) are potent
antimicrobial agents. However, little is known about antimicrobial effects of
biologically synthesized SNPs at molecular level. In the present study, efficacy
of the green microalgae Chlorella vulgaris in biosynthesis of silver
nanoparticles and inhibitory effect of the biosynthesized SNPs on growth and
virulence of Staphylococcus aureus (S. aureus) were investigated. METHODS: Algal
suspension was incubated in the presence of silver nitrate to induce formation of
nanoparticles. The experiment was conducted under a pH range to evaluate pH
effect on the shape and properties of nanoparticles. Characterization was
performed by Transmission Electron Microscopy (TEM), Scanning Electron Microscopy
(SEM), Energy Dispersive Spectrometry (EDS) and X-ray diffraction analysis (XRD).
Moreover, concentration of biosynthesized SNPs was measured by high resolution
ICP-OES spectrometer. Antibacterial effect of SNPs on growth of S. aureus was
evaluated by broth micro-dilution method. Inhibitory effect of SNPs on alpha
hemolysin, a well-known virulence factor of S. aureus was investigated through
real time PCR assay. RESULTS: Spherical SNPs were produced with characteristic
monodispersity at low and neutral pHs; however, in alkaline condition, nanorod
structures were formed. SNPs inhibited growth of S. aureus at concentration of 50
MUg/ml. Alpha hemolysin expression was also effectively inhibited by SNPs
treatment. CONCLUSION: In general, results revealed formation of spherical silver
nanoparticles with inhibitory effects on bacterial growth and antagonist activity
on the expression of alpha hemolysin. Moreover, increase in pH to basic condition
resulted in aggregation of nanoparticles and formation of rod-like
nanostructures.
PMID- 28706607
TI - Evaluation of Factors Affecting Size and Size Distribution of Chitosan
Electrosprayed Nanoparticles.
AB - BACKGROUND: Size and size distribution of polymeric nanoparticles have important
effect on their properties for pharmaceutical application. In this study,
Chitosan nanoparticles were prepared by electrospray method (electrohydrodynamic
atomization) and parameters that simultaneously affect size and/or size
distribution of chitosan nanoparticles were optimized. METHODS: Effect of
formulation/processing three independent formulation/processing parameters,
namely concentration, flow rate and applied voltage was investigated on particle
size and size distribution of generated nanoparticles using a Box-Behnken
experimental design. RESULTS: All the studied factors showed important effects on
average size and size distribution of nanoparticles. A decrease in size and size
distribution was obtainable with decreasing flow rate and concentration and
increasing applied voltage. Eventually, a sample with minimum size and
polydispersity was obtained with polymer concentration, flow rate and applied
voltage values of 0.5 %w/v, 0.05 ml/hr and 15 kV, respectively. The
experimentally prepared nanoparticles, expected having lowest size and size
distribution values had a size of 105 nm, size distribution of 36 and Zeta
potential of 59.3 mV. CONCLUSION: Results showed that optimum condition for
production of chitosan nanoparticles with the minimum size and narrow size
distribution was a minimum value for flow rate and highest value for applied
voltage along with an optimum chitosan concentration.
PMID- 28706608
TI - The Effects of Melilotus officinalis Extract on Expression of Daxx, Nfkb and Vegf
Genes in the Streptozotocin-Induced Rat Model of Sporadic Alzheimer's Disease.
AB - BACKGROUND: Possible mechanisms of Alzheimer Disease (AD) such as inflammation
and oxidative stresses in the brain led us to investigate potential AD
therapeutics of Melilotus officinalis, an herbal extract, with possible role as
an anti-inflammatory and anti-oxidant agent. Among different genes which had
important role in Sporadic AD (SAD), three genes including DAXX, NFkB and VEGF
have shown significant statistical diversity in the brains of Alzheimer patients.
METHODS: These genes were chosen to be investigated for neuroprotective effects
of the extract by comparing the expression level in the hippocampus of Sporadic
AD (SAD) rat model using quantitative polymerase chain reaction (qPCR) in the
treated and untreated groups. In addition, therapeutic effects at the behavioral,
learning and memory level by Morris Water Maze (MWM) test were investigated.
RESULTS: The results represented significant decreased expression in Daxx, Nfkb
and Vegf genes in the SAD rat's model treated with the herbal extract compared to
the Streptozotocin-induced (STZ-induced) rats. Furthermore, no significant
changes were seen in swimming distance and time for finding the hidden platform
in the herbal-treated compared to the STZ-induced group. In memory level, no
significant changes were observed among treated and untreated groups. CONCLUSION:
It seems that the herbal extract may have significant effect on Alzheimer-related
gene expression changes but not on clinical levels.
PMID- 28706609
TI - Distribution of Class I Integron and smqnr Resistance Gene Among Stenotrophomonas
maltophilia Isolated from Clinical Samples in Iran.
AB - BACKGROUND: Stenotrophomonas maltophilia (S. maltophilia) is a multiple
antibiotic-resistant opportunistic pathogen that is being isolated with
increasing frequency from patients with health-care-associated infections. S.
maltophilia is inherently resistant to most of the available antimicrobial
agents. Spread of resistant strains has been attributed, in part, to class I
integrons. In vitro susceptibility studies have shown trimethoprim
sulfamethoxazole and new floroquinolones as two important agents with activity
against these organisms. METHODS: 150 isolates of S. maltophilia were isolated
from clinical samples such as respiratory discharges, sputum, and catheter and
hospital environments. These isolates were also subjected to susceptibility
testing and polymerase chain reaction for four groups of genes including int
encoding integron elements, sulI and sulII encoding trimethoprim-sulfamethoxazole
resistance and smqnr encoding quinolone resistance. RESULTS: The rate of
resistance to trimethoprim-sulfamethoxazole was up to 27 (18%) and the highest
resistance to quinolone family belonged to ofloxacin (20%) and the lowest rate
was for gatifloxacin (16%). The results showed that 14% of isolates contained
integron elements concomitantly with sulI and sulII genes. CONCLUSION: Resistance
rate of S. maltophilia to co-trimoxazole and fluoroquinolones and detection of
integron elements between isolates in this study showed that this rate
corresponded to other data obtained from other studies.
PMID- 28706610
TI - A Novel Variant of OCT4 Entitled OCT4B3 is Expressed in Human Bladder Cancer and
Astrocytoma Cell Lines.
AB - BACKGROUND: Alternative splicing is an important mechanism that regulates gene
expression and function in human cells. OCT4, a crucial pluripotency marker in
embryonic stem/carcinoma cells generates several spliced variants in different
cell types and cancers. The expression of OCT4 in cancers has been challenged in
many studies. The existence of several OCT4 spliced variants and absence of
specific discriminating primers is the main reason of this controversy.
Therefore, using specific primers and discriminating OCT4 variants from each
other might help to reduce these discrepancies in carcinogenesis and stem cell
researches. METHODS: 17 various human cancer, pluripotent and normal cells were
cultured and their RNAs were extracted. Related cDNAs were synthesized and the
expression pattern of OCT4 variants was investigated by RT-PCR assay. PCR
products were cloned into pTZ57R/T vector and their authenticity was confirmed by
DNA sequencing. RESULTS: Expression pattern of OCT4 variants (OCT4A, OCT4B and
OCT4B1) was analyzed by RT-PCR assay and the authenticity of PCR products was
confirmed by DNA sequencing. A novel spliced variant of OCT4 was discovered and
named as OCT4B3. This variant was very similar to OCT4B2 transcript except that
207-nt of exon 1b is lost. Moreover, the expression pattern of OCT4B3 variant was
investigated in 17 human cell types, where its expression was only found in
astrocytoma and bladder cancer cell types 1321N1 and 5637, respectively.
CONCLUSION: OCT4 variants are differentially expressed in various human cancer
cell lines. Moreover, a novel variant of OCT4, OCT4B3, was detected in two human
cancer cell lines of bladder carcinoma (5637) and brain astrocytoma (1321N1) for
the first time.
PMID- 28706611
TI - A Novel Variant in the PAH Gene Causing Phenylketonuria in an Iranian Pedigree.
AB - BACKGROUND: Phenylalanine hydroxylase (PAH) gene is the well-known causative gene
for classic Phenylketonuria (PKU) (OMIM#261600) disease, with more than 500
reported mutations. Through this study, a novel mutation in the PAH gene in an
Iranian pedigree with phenylketonuria was introduced. METHODS: A consanguineous
family with a 10-year old affected girl was referred for genetic analysis.
Mutation screening of all exons and exon-intron boundaries was performed by
Sanger sequencing, and mini haplotype analysis was carried out by genotyping of
Short Tandem Repeat (STR) and Variable Number Tandem Repeat (VNTR) alleles.
RESULTS: Mutation analysis revealed a novel homozygous insertion of a single
adenine nucleotide at position 335 in exon 3 of the PAH gene. Based on the
American College of Medical Genetics and Genomics (ACMG) guidelines, the change
is interpreted as a pathogenic mutation which produces a premature termination
signal (TAA) at codon 113 according to in silico assessments. The mini haplotype
analysis showed that this mutation was linked to STR (15) -VNTR (3). CONCLUSION:
In this study, a novel mutation was reported in a patient who had PKU symptoms
without any previously reported mutations in the PAH gene
(NM_000277.1:p.Asp112Glufs*2) that can be responsible for the classical PKU
phenotype in the Iranian population. Detection of novel mutations indicates
notable allelic heterogeneity of the PAH locus among this population.
PMID- 28706612
TI - Polymorphisms in the Estrogen Receptor Beta Gene and the Risk of Unexplained
Recurrent Spontaneous Abortion.
AB - BACKGROUND: Recurrent Spontaneous Abortion (RSA) is caused by multiple genetic
and non-genetic factors. Around 50% of the RSA cases have no known etiology and
are considered as Unexplained RSA (URSA). Estrogens, via binding to their
receptors, play an important role in female reproduction. This study aimed to
investigate whether single nucleotide polymorphisms (SNPs; +1082G/A, +1730G/A and
rs1256030 C/T) in the estrogen receptor beta (ESR2) gene are associated with
susceptibility to URSA in a population of Iranian women. METHODS: In this case
control study, the study groups consisted of 240 subjects with a history of URSA
and 102 fertile women as controls. Serum levels of follicle stimulating hormone
(FSH), luteinizing hormone (LH), and estradiol (E2) were measured on day 2-3 of
menstrual cycle. Two functional SNPs, +1082G/A (a silent mutation in exon 5) and
+1730G/A (3' untranslated region of the exon 8), and one intron, rs1256030C/T, in
the ESR2 gene were genotyped, using polymerase chain reaction-restriction
fragment length polymorphism (PCR-RFLP) analysis. RESULTS: Serum levels of LH
were significantly increased in URSA women. No significant differences in
distribution of +1082G/A, +1730G/A and rs1256030C/T between URSA and control
groups were observed. CONCLUSION: Our findings suggest that the studied SNPs on
ESR2 gene may not be associated with URSA.
PMID- 28706613
TI - Major Components of Metabolic Parameters and Nutritional Intakes in Different
Genotypes of Adiponectin +276 G>T Gene Polymorphism in Non-Diabetes and Non
Alcoholic Iranian Fatty Liver Patients.
AB - BACKGROUND: Genetic and environmental factors are both involved in the etiology
of Non-Alcoholic Fatty Liver Disease (NAFLD). Among the genetic factors, certain
polymorphisms of adiponectin gene are associated with NAFLD. In the current
study, we investigated the association between metabolic parameters with
different genotypes of adiponectin +276 G>T polymorphism among the Iranian NAFLD
patients, and the effect of nutritional intake with development of NAFLD.
METHODS: In this study, 75 patients with NAFLD and 76 healthy individuals were
enrolled. Dietary intakes were assessed using a semi-quantitative Food-Frequency
Questionnaire (FFQ). Body Mass Index (BMI) and Waist to Hip Ratio (WHR) were
calculated. Biochemical assays including FSG (Fasting Serum Glucose), liver
enzymes, lipid profiles, Malondialdehyde, insulin resistance and Total
Antioxidant Capacity (TAC) were measured after 12 hr fasting. Gene polymorphism
study was done by using of sequencing method. RESULTS: Although, T allele
frequency was more prevalent in patients with NAFLD than control, adiponectin
+276 G>T polymorphism was not associated with risk of NAFLD. Among the metabolic
parameters, TAC in TT genotype was significantly lower 1.44(0.69 to 2.81) p>0.05,
AST in GT, GG genotypes, and ALT in all three genotypes were higher in NAFLD
patients in compared to healthy subjects (p<0.05). Patients with GT genotype have
significantly lower fat consumption and vitamin E intake as compared to control
group with the same genotype (p<0.05). CONCLUSION: In this study, we showed the
association of different genotypes of +276 G>T polymorphism in adiponectin gene
with some metabolic parameters.
PMID- 28706614
TI - World Water Day, 2016; Better Water, Better Jobs for the Unorganized Sector.
PMID- 28706615
TI - Novel Effects of Traditional Wooden Toothbrush on Bowel Motility Symptoms in
Spinal Cord Injury Patients; Findings from a Pilot Quasi-experimental Study.
AB - BACKGROUND: The aim of this study was to investigate the therapeutic effect of
traditional wooden toothbrush usage on most severe constipation, which usually
occurs in spinal cord injury (SCI) patients. METHODS: In a quasi-experimental
study, 61 SCI patients were selected who had injuries in different spinal levels
(cervical, thoracic, and lumbar), and severe constipation from one defection in a
few days to 3 weeks. They were recommended to use traditional wooden toothbrush
for 5 min twice a day, after breakfast and dinner, over a 6 weeks period. Two
proper standard scales, called neurogenic bowel dysfunction (NBD), and
"Constipation Assessment Scale (CAS)," were used for evaluating the changes in
patients' gastrointestinal (GI) habits during the period of using the wooden
toothbrush. Through these scales (NBD and CAS), the therapeutic effects of
traditional wooden toothbrush usage on the severity of constipation before and
after intervention were measured. RESULTS: The mean of NBD and CAS scores were
reduced significantly, from 8.95 +/- 0.78 and 3.34 +/- 0.28; respectively, to
3.03 +/- 0.57 and 1.74 +/- 0.25, after 6 weeks using traditional wooden
toothbrush (P < 0.0001). There was a significant difference in terms of NBD
scores in patients with different levels of injury (P < 0.01), particularly in
patients with thoracic injury, before (10.52 +/- 0.88) and after (3.13 +/- 0.78)
treatment, respectively (P < 0.0001). Eventually, all symptoms of bowel problems
improved significantly after the intervention (P < 0.05). CONCLUSIONS: The use of
traditional wooden toothbrush lead to the improvement of bowel and defecation
problems in SCI patients. Yet more studies, particularly randomized control
clinical trials are needed to investigate the effect of using wooden toothbrush
on other GI reflexes. In addition, if some clinical trials are devised to study
the effects of wooden toothbrush on both conscious and unconscious patients in
ICU, best results are expected to be found on keeping their mouth and teeth
hygiene, as well as, getting rid of their constipations.
PMID- 28706616
TI - Is There Any Association between Glutathione S-transferases M1 and Glutathione S
transferases T1 Gene Polymorphisms and Endometrial Cancer Risk? A Meta-analysis.
AB - Epidemiological evidence on the association between genetic polymorphisms in
glutathione S-transferases M1 (GSTM1) and T1 (GSTT1) genes and risk of
endometrial cancer (EC) has been inconsistent. In this meta-analysis, we seek to
investigate the relationship between GSTM1 and GSTT1 polymorphisms and the risk
of EC. We searched Medline, PubMed, Web of Science, Embase, Chinese National
Knowledge Infrastructure database, and Chinese Biomedical Literature database to
identify eligible studies. The pooled odds ratios (ORs) with 95% confidence
intervals (CIs) for the association were determined using a fixed- or random
effect model. Tests for heterogeneity of the results and sensitivity analyses
were performed. A total of six case-control studies were included in the final
meta-analysis of GSTM1 (1293 cases and 2211 controls) and GSTT1 (1286 cases and
2200 controls) genotypes. Overall, GSTM1 null genotype was not significantly
associated with an increased risk of EC (OR = 1.00, 95% CI = 0.76-1.30, P =
0.982). Similarly, for GSTT1 deletion genotype, we observed no association under
the investigated model in the overall analysis (OR = 0.91, 95% CI = 0.64-1.30, P
= 0.619). Subgroup analysis also showed no significant association between the
GSTM1 null genotype and EC risk in hospital-based design (OR = 1.26, 95% CI =
0.93-1.71, P = 0.131) and no relationship between GSTT1 null genotype with EC
risk in population-based design (OR = 1.18, 95% CI = 0.79-1.76, P = 0.407).
However, GSTM1 null genotype contributed to an increased EC risk in population
based design (OR = 0.76, 95% CI = 0.60-0.97, P = 0.027), while null GSTT1 in
hospital-based studies (OR = 0.70, 95% CI = 0.52-0.93, P = 0.015). The present
meta-analysis suggested that GSTs genetic polymorphisms may not be involved in
the etiology of EC. Large epidemiological studies with the combination of GSTM1
null, GSTT1 null, and design-specific with the development of EC are needed to
prove our findings.
PMID- 28706617
TI - Rare Presentation of Neurofibromatosis and Turner Syndrome in a Pediatric
Patient.
AB - Neurofibromatosis type 1 (NF1) is classically defined by the presence of multiple
cafe-au-lait macules as one of the diagnostic criteria. Turner syndrome (TS) can
also present with cafe-au-lait macules along with short stature. Our patient is
the fifth reported with both NF1 and TS and the first who has been on growth
hormone for short stature associated with TS.
PMID- 28706618
TI - Isolated Ileal Perforation in Infancy: A Lethal Initial Presentation of
Hirschsprung's Disease.
AB - Arare case of ileal perforation, as a fatal initial presentation of total colonic
aganglionosis (TCA) in infancy is reported. A 10-week-old boy, was brought to the
emergency department with symptoms of complicated intestinal obstruction. He
looked ill, was lethargic, markedly dehydrated and had a severely distended
abdomen. An abdominal X-ray revealed multiple air fluid levels seen in a
distended small intestine. During exploratory laparotomy the ileum was massively
dilated with distal segment perforation. Ileal perforation repair was performed.
A totally collapsed microcolon was identified. Biopsies were taken from the high
rectum, sigmoid and hepatic flexure. Appendectomy and ileostomy were performed.
All biopsies, as well as the appendix, showed absence of ganglion cells. Despite
this procedure the patient progressively deteriorated and later died due to
sepsis. Ileal perforation in infants is a rare, but potentially fatal initial
presentation of TCA. Early detection is essential to prevent life-threatening
complications.
PMID- 28706619
TI - Kawasaki Disease Presenting with Bloody Diarrhea and Acute Renal Failure: First
Case.
AB - Kawasaki disease (KD) is an acute febrile vasculitis of an unknown cause. It
affects children <5 year of age, even if cases over 5 years old have been also
reported. It is the commonest cause of acquired heart diseases in children which
may lead to serious morbidity and mortality. The complications and mortality
increase when the diagnosis is delayed. One of the main reasons leading to
delayed diagnosis and consequent delayed treatment is the unusual presentation of
KD. Its unusual manifestations have been increasingly reported to jeopardize the
timely diagnosis and proper treatment. As there is not yet available blood test
to diagnose it, low threshold should be taken into account for considering KD,
when the clinical criteria are not typical. KD with renal manifestations is
infrequently described. We present and discuss a case of an unusual presentation
of KD presenting as bloody diarrhea and acute renal failure.
PMID- 28706620
TI - Adams-Oliver Syndrome with Unusual Central Nervous System Findings and an
Extrahepatic Portosystemic Shunt.
AB - We report a case of a premature neonate girl with scalp and skull defects and
brachydactyly of the feet consistent with an Adams-Oliver syndrome (AOS). The
patient had central nervous system abnormalities, such as periventricular
calcifications, hypoplastic corpus callosum, and bilateral hemispheric
corticosubcortical hemorrhagic lesions. A muscular ventricular septal defect and
a portosystemic shunt were diagnosed. To our knowledge, this is the first report
of congenital supratentorial grey-white matter junction lesions without dural
sinus thrombosis in association with AOS. Some of these lesions may be secondary
to birth trauma (given the skull defect) whilst others have a watershed location,
perhaps as further evidence of vascular disruption and decreased perfusion during
critical periods of fetal brain development as the previously proposed
pathogenesis of this syndrome.
PMID- 28706621
TI - Pediatric Laparoscopy and Adaptive Oxygenation and Hemodynamic Changes.
AB - Adaptive changes in oxygenation and hemodynamics are evaluated during pediatric
laparoscopy. The children underwent laparoscopy (LAP Group, n=20) or open surgery
(Open Group, n=10). Regional cerebral (rScO2) and peripheral oxygen saturation
(SpO2), heart rate (HR), diastolic (DP) and systolic pressure (SP) were monitored
at different intervals: basal (T0); anesthesia induction (T1); CO2PP insufflation
(T2); surgery (T3); CO2PP cessation (T4); before extubation (T5). At T1, in both
the LAP and Open groups significant changes in rScO2, DP and SP were recorded
compared with T0; a decrease in SatO2 was also observed at T5. In the LAP group,
at T2, changes in HR related to CO2PP pressure and in DP and SP related to IAP
were noted; at T4, a SP change associated with CO2PP desufflation was recorded.
Open group, at T3 and T5 showed lower rScO2 values compared with T1.
Pneuperitoneum and anesthesia are influent to induce hemodynamics changes during
laparoscopy.
PMID- 28706622
TI - Patient understanding of liver cirrhosis and improvement using multimedia
education.
AB - OBJECTIVE: For patients to engage with the long-term management of liver
cirrhosis, sufficient understanding of their condition is essential. The aim of
this study was to assess baseline patient knowledge and to test whether a
condition-specific multimedia screencast could improve this. DESIGN: Service
quality improvement study. SETTING: A UK tertiary liver centre. Patients were
recruited during 12 general hepatology outpatient clinics. PATIENTS: Fifty-two
patients with liver cirrhosis were included. Sixty-two per cent were male; their
median age was 56 years and their median clinic attendance period was 3 years.
INTERVENTIONS: Participants completed a baseline questionnaire assessing their
knowledge of the management and complications of cirrhosis. They then watched a
tailored screencast discussing this condition, which had been developed by expert
hepatologists in collaboration with patient representatives. Knowledge was
reassessed using a new copy of the original questionnaire after an interval of at
least one month. MAIN OUTCOME MEASURES: Patient scores on knowledge
questionnaires at baseline and follow-up. RESULTS: Fifty-two patients achieved a
median score of 25.0% before viewing the screencast. Thirty-five patients then
completed a follow-up questionnaire after an interval period. The median
questionnaire score in this group improved from 25.0% to 66.7%; an increase of
41.7% compared with baseline (p<0.001). CONCLUSIONS: Despite regular review at a
specialist clinic, participants had poor baseline knowledge of liver cirrhosis.
Delivering information by screencast led to a significant improvement. We
therefore present an effective way to empower patients with accurate, up-to-date
and retainable information that can easily be translated to many other
conditions.
PMID- 28706623
TI - Stabilization of H3+ in the high pressure crystalline structure of H n Cl (n = 2
7).
AB - The particle-swarm optimization method has been used to predict the stable high
pressure structures up to 300 GPa of hydrogen-rich group 17 chlorine (H n Cl, n =
2-7) compounds. In comparison to the group 1 and 2 hydrides, the structural
modification associated with increasing pressure and hydrogen concentration is
much less dramatic. The polymeric HCl chains already present in the low
temperature phase under ambient pressure persist in all the high pressure
structures. No transfer of electrons from the chlorine atoms into the
interstitial sites is found. This indicates the chemical bonding at high pressure
in group 17 elements is fundamentally different from the alkali and alkaline
elements. It is found that almost perfectly triangular H3+ ions can be stabilized
in the crystalline structure of H5Cl.
PMID- 28706624
TI - Ligand functionalization as a deactivation pathway in a fac-Ir(ppy)3-mediated
radical addition.
AB - Knowledge of the kinetic behavior of catalysts under synthetically relevant
conditions is vital for the efficient use of compounds that mediate important
transformations regardless of their composition or driving force. In particular,
these data are of great importance to add perspective to the growing number of
applications of photoactive transition metal complexes. Here we present kinetic,
synthetic, and spectroscopic evidence of the mechanistic behavior of fac-Ir(ppy)3
in a visible light-mediated radical addition to 3-methylindole, demonstrating the
instability of fac-Ir(ppy)3 under these conditions. During the reaction, rapid in
situ functionalization of the photocatalyst occurs, eventually leading to
deactivation. These findings demonstrate a conceivable deactivation process for
catalytic single electron reactions in the presence of radicophilic ligands.
Attempts to inhibit photocatalyst deactivation through structural modification
provide further insight into catalyst selection for a given system of interest.
PMID- 28706625
TI - Facile synthesis of oligoyne amphiphiles and their rotaxanes.
AB - Carbon-rich organic compounds containing a series of conjugated triple bonds
(oligoynes) are relevant synthetic targets, but an improved access to oligoynes
bearing functional groups would be desirable. Here, we report the straightforward
synthesis of two series of oligoyne amphiphiles with glycoside or carboxylate
polar head groups, investigate their self-assembly behavior in aqueous media, and
their use as precursors for the formation of oligoyne rotaxanes with cyclodextrin
hosts. To this end, we employed mono-, di-, or triacetylenic building blocks that
gave access to the corresponding zinc acetylides in situ and allowed for the
efficient elongation of the oligoyne segment in few synthetic steps via a Negishi
coupling protocol. Moreover, we show that the obtained oligoyne derivatives can
be deprotected to yield the corresponding amphiphiles. Depending on their head
groups, the supramolecular self-assembly of these amphiphiles gave rise to
different types of carbon-rich colloidal aggregates in aqueous media.
Furthermore, their amphiphilicity was exploited for the preparation of novel
oligoyne cyclodextrin rotaxanes using simple host-guest chemistry in water.
PMID- 28706626
TI - History-dependent ion transport through conical nanopipettes and the implications
in energy conversion dynamics at nanoscale interfaces.
AB - The dynamics of ion transport at nanostructured substrate-solution interfaces
play vital roles in high-density energy conversion, stochastic chemical sensing
and biosensing, membrane separation, nanofluidics and fundamental
nanoelectrochemistry. Further advancements in these applications require a
fundamental understanding of ion transport at nanoscale interfaces. The
understanding of the dynamic or transient transport, and the key physical process
involved, is limited, which contrasts sharply with widely studied steady-state
ion transport features at atomic and nanometer scale interfaces. Here we report
striking time-dependent ion transport characteristics at nanoscale interfaces in
current-potential (I-V) measurements and theoretical analyses. First, a unique
non-zero I-V cross-point and pinched I-V curves are established as signatures to
characterize the dynamics of ion transport through individual conical
nanopipettes. Second, ion transport against a concentration gradient is regulated
by applied and surface electrical fields. The concept of ion pumping or
separation is demonstrated via the selective ion transport against concentration
gradients through individual nanopipettes. Third, this dynamic ion transport
process under a predefined salinity gradient is discussed in the context of
nanoscale energy conversion in supercapacitor type charging-discharging, as well
as chemical and electrical energy conversion. The analysis of the emerging
current-potential features establishes the urgently needed physical foundation
for energy conversion employing ordered nanostructures. The elucidated mechanism
and established methodology can be generalized into broadly-defined nanoporous
materials and devices for improved energy, separation and sensing applications.
PMID- 28706627
TI - Fe(iii) phytate metallogel as a prototype anhydrous, intermediate temperature
proton conductor.
AB - A proton conducting metallogel [FNPA; ferric nitrate (FN)-phytic acid (PA)] is
synthesized by immobilizing a protogenic ligand (phytic acid) using iron(iii)
nitrate in DMF. The xerogel shows high proton conductivity of 2.4 * 10-2 S cm-1
at 120 degrees C, the best value known among all metal organic materials (MOMs).
Marking the first such attempt in MOMs, an electrode made using the xerogel
showed a power density of 0.94 mW cm-2 at 0.6 V under dry fuel cell conditions.
PMID- 28706628
TI - A high-spin square-planar Fe(ii) complex stabilized by a trianionic pincer-type
ligand and conclusive evidence for retention of geometry and spin state in
solution.
AB - Square-planar high-spin Fe(ii) molecular compounds are rare and the only three
non-macrocyclic or sterically-driven examples reported share a common FeO4 core.
Using an easily modifiable pincer-type ligand, the successful synthesis of the
first compound of this type that breaks the FeO4 motif was achieved. In addition,
we present the first evidence that geometry and spin state persist in solution.
Extensive characterization includes the first high-field EPR and variable
field/temperature Mossbauer spectra for this class of compounds. Analysis of the
spectroscopic data indicates this complex exhibits a large and positive zero
field splitting tensor. Furthermore, the unusually small DeltaEQ value determined
for this compound is rationalized on the basis of DFT calculations.
PMID- 28706629
TI - Reversible photo-induced trap formation in mixed-halide hybrid perovskites for
photovoltaics.
AB - We report on reversible, light-induced transformations in (CH3NH3)Pb(Br x I1-x
)3. Photoluminescence (PL) spectra of these perovskites develop a new, red
shifted peak at 1.68 eV that grows in intensity under constant, 1-sun
illumination in less than a minute. This is accompanied by an increase in sub
bandgap absorption at ~1.7 eV, indicating the formation of luminescent trap
states. Light soaking causes a splitting of X-ray diffraction (XRD) peaks,
suggesting segregation into two crystalline phases. Surprisingly, these photo
induced changes are fully reversible; the XRD patterns and the PL and absorption
spectra revert to their initial states after the materials are left for a few
minutes in the dark. We speculate that photoexcitation may cause halide
segregation into iodide-rich minority and bromide-enriched majority domains, the
former acting as a recombination center trap. This instability may limit
achievable voltages from some mixed-halide perovskite solar cells and could have
implications for the photostability of halide perovskites used in
optoelectronics.
PMID- 28706630
TI - Probing the second dehydrogenation step in ammonia-borane dehydrocoupling:
characterization and reactivity of the key intermediate, B
(cyclotriborazanyl)amine-borane.
AB - While thermolysis of ammonia-borane (AB) affords a mixture of aminoborane- and
iminoborane oligomers, the most selective metal-based catalysts afford
exclusively cyclic iminoborane trimer (borazine) and its B-N cross-linked
oligomers (polyborazylene). This catalysed dehydrogenation sequence proceeds
through a branched cyclic aminoborane oligomer assigned previously as trimeric B
(cyclodiborazanyl)amine-borane (BCDB). Herein we utilize multinuclear NMR
spectroscopy and X-ray crystallography to show instead that this key intermediate
is actually tetrameric B-(cyclotriborazanyl)amine-borane (BCTB) and a method is
presented for its selective synthesis from AB. The reactivity of BCTB upon
thermal treatment as well as catalytic dehydrogenation is studied and discussed
with regard to facilitating the second dehydrogenation step in AB
dehydrocoupling.
PMID- 28706631
TI - Delivery of mirror image polypeptides into cells.
AB - Mirror image peptides have unique stability and immunogenic properties in
mammals, making them attractive agents to investigate. Their properties inside
cells have been mostly unexplored because biopolymers are difficult to transport
across cellular membranes. Here, we used protective antigen (PA) from anthrax
toxin to deliver mirror image polypeptide cargo into the cytosol of mammalian
cells when conjugated to the C-terminus of the PA-binding domain of lethal
factor, LFN. We found mirror image polypeptides and proteins were translocated as
efficiently into cells as their L counterparts. Once in the cytosol, by the use
of western blot, we found that d peptides at the C-terminus of LFN were able to
achieve higher steady state concentrations when compared to the l-peptide
conjugate. With this platform, we delivered a d-peptide MDM2 antagonist to
disrupt the p53/MDM2 interaction in cancer cells. For the first time, we show the
PA/LFN system is adaptable for the intracellular delivery of mirror image
peptides and proteins.
PMID- 28706632
TI - A macrocycle-assisted nanoparticlization process for bulk Ag2S.
AB - We report herein a new nanoparticlization process for the bulk-to-nano
transformation of Ag2S by incorporating both top-down and bottom-up approaches.
Bulk Ag2S was dissolved in solution with the assistance of a macrocyclic ligand,
hexamethylazacalix[6]pyridine (Py[6]), to produce polynuclear silver sulfide
cluster aggregates. All Ag-S cluster aggregates obtained in three crystalline
complexes were protected by Py[6] macrocycles. Removing the protective Py[6]
macrocycles by protonation led to the generation of unconventional Ag-S
nanoparticles with a large energy gap. Theoretical calculations by a hybrid DFT
method demonstrated that the silver sulfide clusters with high Ag/S ratio
exhibited more localized HOMO-LUMO orbitals, which consequently enlarged their
band gap energies. These experimental and theoretical studies broaden our
understanding of the fabrication of nanomaterials by virtue of the advantages of
both bottom-up and top-down methods and meanwhile provide a viable means of
adjusting the band gap of binary nanomaterials independent of their size.
PMID- 28706633
TI - Diagnosing the miR-141 prostate cancer biomarker using nucleic acid
functionalized CdSe/ZnS QDs and telomerase.
AB - The microRNA, miR-141, is a promising biomarker for prostate cancer. We implement
here a two-step sensing platform for the sensitive detection of miR-141. The
first step involves the use of semiconductor CdSe/ZnS quantum dots (QDs) modified
by FRET quencher-functionalized nucleic acids, that include the recognition
sequence for miR-141 and a telomerase primer sequence for the second step of the
analytical platform. Subjecting the probe-modified QDs to miR-141, in the
presence of duplex specific nuclease, DSN, leads to the formation of a miR
141/probe duplex and to its DSN-mediated cleavage, while regenerating the miR
141. The DSN-induced cleavage of the quencher units leads to the activation of
the fluorescence of the QDs, thus allowing the optical detection of miR-141 with
a sensitivity corresponding to 1.0 * 10-12 M. The nucleic acid residues
associated with the QDs after cleavage of the probe nucleic acids by DSN act as
primers for telomerase. The subsequent telomerase/dNTPs-stimulated elongation of
the primer units forms G-quadruplex telomer chains. Incorporation of hemin in the
resulting G-quadruplex telomer chains yields horseradish peroxidase-mimicking
DNAzyme units, that catalyze the generation of chemiluminescence in the presence
of luminol/H2O2. The resulting chemiluminescence intensities provide a readout
signal for miR-141, DL = 2.8 * 10-13 M. The first step of the sensing platform is
non-selective toward miR-141 and the resulting fluorescence may be considered
only as an indicator for the existence of miR-141. The second step in the sensing
protocol, involving telomerase, provides a selective chemiluminescence signal for
the existence of miR-141. The two-step sensing platform is implemented for the
analysis of miR-141 in serum samples from healthy individuals and prostate cancer
carriers. Impressive discrimination between healthy individuals and prostate
cancer carriers is demonstrated.
PMID- 28706634
TI - Chiral tether-mediated stabilization and helix-sense control of complementary
metallo-double helices.
AB - A series of novel PtII-linked double helices were prepared by inter- or
intrastrand ligand-exchange reactions of the complementary duplexes composed of
chiral or achiral amidine dimer and achiral carboxylic acid dimer strands joined
by trans-PtII-acetylide complexes with PPh3 ligands using chiral and achiral
chelating diphosphines. The structure and stability of the PtII-linked double
helices were highly dependent on the diphosphine structures. An interstrand
ligand exchange took place with chiral and achiral 1,3-diphosphine-based ligands,
resulting in trans-PtII-bridged double helices, whose helical structures were
quite stable even in dimethyl sulfoxide (DMSO) due to the interstrand cross-link,
whereas a 1,2-diphosphine-based ligand produced non-cross-linked cis-PtII-linked
duplexes, resulting from an intrastrand ligand-exchange that readily dissociated
into single strands in DMSO. When enantiopure 1,3-diphosphine-based ligands were
used, the resulting trans-PtII-bridged double helices adopted a preferred-handed
helical sense biased by the chirality of the bridged diphosphines. Interestingly,
the interstrand ligand exchange with racemic 1,3-diphosphine toward an optically
active PtII-linked duplex, composed of chiral amidine and achiral carboxylic acid
strands, was found to proceed in a diastereoselective manner, thus forming
complete homochiral trans-PtII-bridged double helices via a unique chiral self
sorting.
PMID- 28706635
TI - Template-directed ligation on repetitive DNA sequences: a chemical method to
probe the length of Huntington DNA.
AB - Several genomic disorders are caused by an excessive number of DNA triplet
repeats. We developed a DNA-templated reaction in which product formation occurs
only when the number of repeats exceeds a threshold indicative for the outbreak
of Chorea Huntington. The combined use of native chemical PNA ligation and
auxiliary DNA probes enabled reactions on templates obtained from human genomic
DNA.
PMID- 28706636
TI - Matrix coating assisted by an electric field (MCAEF) for enhanced tissue imaging
by MALDI-MS.
AB - A novel technique, termed matrix coating assisted by an electric field (MCAEF),
for enhancing tissue imaging by matrix-assisted laser desorption/ionization mass
spectrometry (MALDI-MS) was developed in this study. In this technique a static
and uniform electric field is applied to sliced tissue sections during matrix
spray-coating, resulting in the enrichment of positively or negatively chargeable
analytes in the MALDI matrix layer. Experimental results show that MCAEF not only
increased the sensitivity of lipid and protein detection across the board in the
subsequent MALDI-MS analyses, but also resulted in successful imaging of a larger
number of analytes. MALDI imaging enhancement with MCAEF was observed for various
tissues (rat liver, rat brain, and porcine adrenal gland) and with different
MALDI matrices (e.g., quercetin, 2-mercaptobenzothiazole, dithranol, 9
aminoacridine, and sinapinic acid) and the sensitivity increases were independent
of the solvent compositions and pH values of the matrix solutions. Taking rat
brain as an example, MCAEF led to the on-tissue detection and imaging of 648
identified lipids by combining positive and negative ion detection by MALDI
Fourier transform ion cyclotron resonance MS and with quercetin as the matrix, as
compared to only 344 lipids without MCAEF. For protein imaging, up to 232 protein
signals were successfully detected in rat brain tissue sections by MALDI-time-of
flight MS within a mass range of 3500 to 37 000 Da, as compared to 119 without
MCAEF. MCAEF also enabled the detection of higher molecular-weight proteins.
These results demonstrate the advantages of MCAEF for overall performance
improvements in MALDI imaging and we believe that this technique has the
potential to become a standard practice for MALDI tissue imaging.
PMID- 28706637
TI - Photoaffinity labeling of transcription factors by DNA-templated crosslinking.
AB - Characterization of transcription factor-DNA interaction is of high importance in
elucidating the molecular mechanisms of gene transcriptions. DNA-based affinity
probes were developed to capture and identify transcription factors by covalent
crosslinking; however, the requirement of a crosslinker on the affinity probe
remains a disadvantage, as the crosslinker itself often interferes with the
protein-DNA interactions. We report a dual-probe method able to capture DNA
binding transcription factors with unmodified protein-binding sites in scenarios
where conventional probes have failed. We have also shown the method's converse
application in selecting specific transcription factor-binding DNA sequences from
a probe library and its extension to studying proteins recognizing epigenetic
marks. This study may provide a new tool for exploring DNA-binding proteins in
biology.
PMID- 28706638
TI - Non-equilibrium cobalt(iii) "click" capsules.
AB - Cobalt(iii) tetrahedral capsules have been prepared using an assembly-followed-by
oxidation protocol from a cobalt(ii) precursor and a readily derivatizable
pyridyl-triazole ligand system. Experiments designed to probe the constitutional
dynamics show that these architectures are in a non-equilibrium state. A
preliminary investigation into the host-guest chemistry of a water-soluble
derivative shows it can bind and differentiate a range of different neutral
organic molecules. The stability of this ensemble also permits the study of guest
binding at high salt concentrations.
PMID- 28706639
TI - A sialic acid-targeted near-infrared theranostic for signal activation based
intraoperative tumor ablation.
AB - Agents enabling tumor staging are valuable for cancer surgery. Herein, a
targetable sialic acid-armed near-infrared profluorophore (SA-pNIR) is reported
for fluorescence guided tumor detection. SA-pNIR consists of a sialic acid entity
effective for in vivo tumor targeting and a profluorophore which undergoes
lysosomal acidity-triggered fluorogenic isomerization. SA-pNIR displays a number
of advantageous biomedical properties in mice, e.g. high tumor-to-normal tissue
signal contrast, long-term retention in tumors and low systemic toxicity. In
addition, SA-pNIR effectively converts NIR light into cytotoxic heat in cells,
suggesting tumor-activatable photothermal therapy. With high performance tumor
illumination and lysosome-activatable photothermal properties, SA-pNIR is a
promising agent for detection and photothermal ablation of surgically exposed
tumors.
PMID- 28706640
TI - Protein ubiquitination and formation of polyubiquitin chains without ATP, E1 and
E2 enzymes.
AB - Studying protein ubiquitination is difficult due to the complexity of the E1-E2
E3 ubiquitination cascade. Here we report the discovery that C-terminal ubiquitin
thioesters can undergo direct transthiolation with the catalytic cysteine of the
model HECT E3 ubiquitin ligase Rsp5 to form a catalytically active Rsp5~ubiquitin
thioester (Rsp5~Ub). The resulting Rsp5~Ub undergoes efficient
autoubiquitination, ubiquitinates protein substrates, and synthesizes
polyubiquitin chains with native Ub isopeptide linkage specificity. Since the
developed chemical system bypasses the need for ATP, E1 and E2 enzymes while
maintaining the native HECT E3 mechanism, we named it "Bypassing System" (ByS).
Importantly, ByS provides direct evidence that E2 enzymes are dispensable for K63
specific isopeptide bond formation between ubiquitin molecules by Rsp5 in vitro.
Additionally, six other E3 enzymes including Nedd4-1, Nedd4-2, Itch, and Wwp1
HECT ligases, along with Parkin and HHARI RBR ligases processed Ub thioesters
under ByS reaction conditions. These findings provide general mechanistic
insights on protein ubiquitination, and offer new strategies for assay
development to discover pharmacological modulators of E3 enzymes.
PMID- 28706641
TI - Functionalized graphene-based biomimetic microsensor interfacing with living
cells to sensitively monitor nitric oxide release.
AB - It is a great challenge to develop electrochemical sensors with superior
sensitivity that concurrently possess high biocompatibility for monitoring at the
single cell level. Herein we report a novel and reusable biomimetic micro
electrochemical sensor array with nitric oxide (NO) sensing-interface based on
metalloporphyrin and 3-aminophenylboronic acid (APBA) co-functionalized reduced
graphene oxide (rGO). The assembling of high specificity catalytic but semi
conductive metalloporphyrin with high electric conductive rGO confers the sensor
with sub-nanomolar sensitivity. Further coupling with the small cell-adhesive
molecule APBA obviously enhances the cytocompatibility of the microsensor without
diminishing the sensitivity, while the reversible reactivity between APBA and
cell membrane carbohydrates allows practical reusability. The microsensor was
successfully used to sensitively monitor, in real-time, the release of NO
molecules from human endothelial cells being cultured directly on the sensor.
This demonstrates its potential application in the detection of NO with very low
bioactive concentrations for the better understanding of its physiological
function and for medical tracking of patient states.
PMID- 28706642
TI - Highly sensitive and multiplexed analysis of CpG methylation at single-base
resolution with ligation-based exponential amplification.
AB - DNA methylation is a primary epigenetic mechanism for transcriptional regulation
during normal development and the occurrence of diseases, including cancers. DNA
methylation has been increasingly utilized as a biomarker for cancer detection
and differential diagnosis. Generally, one type of cancer is associated with
several CpG methylation sites and detection of multiplexed CpG methylation can
greatly improve the accuracy of cancer diagnosis. In this paper, we have
developed a novel ligase chain reaction (LCR)-based method for multiplexed
detection of CpG methylation in genomic DNA at single-base resolution. By
rationally designing the two pairs of DNA probes for LCR, the bisulfite-treated
methylated DNA target can be exponentially amplified by thermal cycling of the
ligation reaction, in which one-base mismatch can be discriminated against, and
thus high sensitivity and specificity for the detection of DNA methylation can be
achieved. The LCR-based method can accurately determine as low as 10 aM
methylated DNA fragment and 10 ng methylated genomic DNA. 0.1% methylated DNA can
be detected in the presence of a large excess of unmethylated DNA. Moreover, by
simply encoding one of the DNA probes in the LCR with a different length of
poly(A) for detection of methylation at different CpG sites, the CpG methylation
at different sites can produce LCR products with different lengths, and thus, can
be simultaneously detected with one-tube LCR amplification and separation by
capillary electrophoresis.
PMID- 28706643
TI - A rationally designed small molecule for identifying an in vivo link between
metal-amyloid-beta complexes and the pathogenesis of Alzheimer's disease.
AB - Multiple factors, including amyloid-beta (Abeta), metals, and reactive oxygen
species (ROS), are involved in the development of Alzheimer's disease (AD). Metal
ions can interact with Abeta species generating toxic oligomers and ROS in vitro;
however, the involvement of metal-Abeta complexes in AD pathology in vivo remains
unclear. To solve this uncertainty, we have developed a chemical tool (L2-b) that
specifically targets metal-Abeta complexes and modulates their reactivity (i.e.,
metal-Abeta aggregation, toxic oligomer formation, and ROS production). Through
the studies presented herein, we demonstrate that L2-b is able to specifically
interact with metal-Abeta complexes over metal-free Abeta analogues, redirect
metal-Abeta aggregation into off-pathway, nontoxic less structured Abeta
aggregates, and diminish metal-Abeta-induced ROS production, overall mitigating
metal-Abeta-triggered toxicity, confirmed by multidisciplinary approaches. L2-b
is also verified to enter the brain in vivo with relative metabolic stability.
Most importantly, upon treatment of 5XFAD AD mice with L2-b, (i) metal-Abeta
complexes are targeted and modulated in the brain; (ii) amyloid pathology is
reduced; and (iii) cognition deficits are significantly improved. To the best of
our knowledge, by employing an in vivo chemical tool specifically prepared for
investigating metal-Abeta complexes, we report for the first time experimental
evidence that metal-Abeta complexes are related directly to AD pathogenesis.
PMID- 28706644
TI - Principal factors that determine the extension of detection range in molecular
beacon aptamer/conjugated polyelectrolyte bioassays.
AB - A strategy to extend the detection range of weakly-binding targets is reported
that takes advantage of fluorescence resonance energy transfer (FRET)-based
bioassays based on molecular beacon aptamers (MBAs) and cationic conjugated
polyelectrolytes (CPEs). In comparison to other aptamer-target pairs, the aptamer
based adenosine triphosphate (ATP) detection assays are limited by the relatively
weak binding between the two partners. In response, a series of MBAs were
designed that have different stem stabilities while keeping the constant ATP
specific aptamer sequence in the loop part. The MBAs are labeled with a
fluorophore and a quencher at both termini. In the absence of ATP, the hairpin
MBAs can be opened by CPEs via a combination of electrostatic and hydrophobic
interactions, showing a FRET-sensitized fluorophore signal. In the presence of
ATP, the aptamer forms a G-quadruplex and the FRET signal decreases due to
tighter contact between the fluorophore and quencher in the ATP/MBA/CPE triplex
structure. The FRET-sensitized signal is inversely proportional to [ATP]. The
extension of the detection range is determined by the competition between opening
of the ATP/MBA G-quadruplex by CPEs and the composite influence by ATP/aptamer
binding and the stem interactions. With increasing stem stability, the weak
binding of ATP and its aptamer is successfully compensated to show the resistance
to disruption by CPEs, resulting in a substantially broadened detection range
(from millimolar up to nanomolar concentrations) and a remarkably improved limit
of detection. From a general perspective, this strategy has the potential to be
extended to other chemical- and biological-assays with low target binding
affinity.
PMID- 28706645
TI - Stimuli-responsive hybrid materials: breathing in magnetic layered double
hydroxides induced by a thermoresponsive molecule.
AB - A hybrid magnetic multilayer material of micrometric size, with highly
crystalline hexagonal crystals consisting of CoAl-LDH ferromagnetic layers
intercalated with thermoresponsive 4-(4-anilinophenylazo)benzenesulfonate (AO5)
molecules diluted (ratio 9 : 1) with a flexible sodium dodecylsulphate (SDS)
surfactant has been obtained. The resulting material exhibits thermochromism
attributable to the isomerization between the azo (prevalent at room temperature)
and the hydrazone (favoured at higher temperatures) tautomers, leading to a
thermomechanical response. In fact, these crystals exhibited thermally induced
motion triggering remarkable changes in the crystal morphology and volume. In
situ variable temperature XRD of these thin hybrids shows that the reversible
change into the two tautomers is reflected in a shift of the position of the
diffraction peaks at high temperatures towards lower interlayer spacing for the
hydrazone form, as well as a broadening of the peaks reflecting lower
crystallinity and ordering due to non-uniform spacing between the layers. These
structural variations between room temperature (basal spacing (BS) = 25.91 A) and
100 degrees C (BS = 25.05 A) are also reflected in the magnetic properties of
the layered double hydroxide (LDH) due to the variation of the magnetic coupling
between the layers. Overall, our study constitutes one of the few examples
showing fully reversible thermo-responsive breathing in a 2D hybrid material. In
addition, the magnetic response of the hybrid can be modulated due to the
thermotropism of the organic component that, by influencing the distance and in
plane correlation of the inorganic LDH, modulates the magnetism of the CoAl-LDH
sheets in a certain range.
PMID- 28706646
TI - Air-stable ambipolar field-effect transistor based on a solution-processed
octanaphthoxy-substituted tris(phthalocyaninato) europium semiconductor with high
and balanced carrier mobilities.
AB - Simple solvent vapor annealing over QLS film-based OFET devices fabricated from
(Pc)Eu[Pc(ONh)8]Eu[Pc(ONh)8] led to a high and balanced ambipolar performance
that has never been observed for small molecule single-component-based solution
processed devices, with mobilities of 1.71 and 1.25 cm2 V-1 s-1 for holes and
electrons, respectively, under ambient conditions.
PMID- 28706647
TI - DNA-based visual majority logic gate with one-vote veto function.
AB - A molecular logic gate is a basic element and plays a key role in molecular
computing. Herein, we have developed a label-free and enzyme-free three-input
visual majority logic gate which is realized for the first time according to DNA
hybridization only, without DNA replacement and enzyme catalysis. Furthermore, a
one-vote veto function was integrated into the DNA-based majority logic gate, in
which one input has priority over other inputs. The developed system can also
implement multiple basic and cascade logic gates.
PMID- 28706648
TI - Mesoporous silica nanoparticles for 19F magnetic resonance imaging, fluorescence
imaging, and drug delivery.
AB - Multifunctional mesoporous silica nanoparticles (MSNs) are good candidates for
multimodal applications in drug delivery, bioimaging, and cell targeting. In
particular, controlled release of drugs from MSN pores constitutes one of the
superior features of MSNs. In this study, a novel drug delivery carrier based on
MSNs, which encapsulated highly sensitive 19F magnetic resonance imaging (MRI)
contrast agents inside MSNs, was developed. The nanoparticles were labeled with
fluorescent dyes and functionalized with small molecule-based ligands for active
targeting. This drug delivery system facilitated the monitoring of the
biodistribution of the drug carrier by dual modal imaging (NIR/19F MRI).
Furthermore, we demonstrated targeted drug delivery and cellular imaging by the
conjugation of nanoparticles with folic acid. An anticancer drug (doxorubicin,
DOX) was loaded in the pores of folate-functionalized MSNs for intracellular drug
delivery. The release rates of DOX from the nanoparticles increased under acidic
conditions, and were favorable for controlled drug release to cancer cells. Our
results suggested that MSNs may serve as promising 19F MRI-traceable drug
carriers for application in cancer therapy and bio-imaging.
PMID- 28706649
TI - Dynamic tracking of pathogenic receptor expression of live cells using pyrenyl
glycoanthraquinone-decorated graphene electrodes.
AB - Expression of specific transmembrane receptors by cells frequently represents an
important signature of diseases, but this dynamic event can hardly be monitored
directly with live cells due to the limitation of current biochemical techniques.
Here we develop a pyrenyl glycoanthraquinone construct that can be firmly
immobilized on a graphene-spotted screen printed electrode via strong pi
interactions. The inherent current signal produced by the surface-confined
glycoquinone can be used to detect selective sugar-protein recognitions with
simple electrochemical techniques and portable facilities. Importantly, we
demonstrate that the level of pathogenic receptors expressed by different types
of live cells can be tracked with the electrode system in a label-free manner,
providing a useful tool for the on-demand disease diagnosis as well as basic
biochemical studies.
PMID- 28706650
TI - A carbohydrate-grafted nanovesicle with activatable optical and acoustic
contrasts for dual modality high performance tumor imaging.
AB - Activatable molecular systems enabling precise tumor localization are valuable
for complete tumor resection. Herein, we report sialic acid-capped polymeric
nanovesicles encapsulating the near infrared profluorophore (pNIR@P@SA) for
lysosome activation based dual modality tumor imaging. The probe features surface
anchored sialic acid for tumor targeting and a core of near infrared
profluorophore (pNIR) which undergoes lysosomal acidity triggered isomerization
to give optical and optoacoustic signals upon cell internalization. Imaging
studies reveal high-efficiency uptake and signal activation of pNIR@P@SA in
subcutaneous tumors and millimeter-sized liver tumor foci in mice. The high tumor
to-healthy organ signal contrasts and discernment of tiny liver tumors from
normal liver tissues validate the potential of pNIR@P@SA for high performance
optical and optoacoustic imaging guided tumor resection.
PMID- 28706651
TI - Brushing up from "anywhere" under sunlight: a universal surface-initiated
polymerization from polydopamine-coated surfaces.
AB - We describe a simple yet extremely versatile and generalized surface polymer
modification approach based on a surface initiated polymerization from a
polydopamine (PDA) layer. PDA deposits on virtually any substrate independent of
specific surface chemistries and can act as a photoinitiating layer to initiate
the radical polymerization of a variety of (methyl)acrylic/styrene monomers. It
does not require any metal/ligand catalyst, additional photoinitiator or dye
sensitizer. Another attractive feature of this novel strategy is the ability to
spatially control the architectures (pattern, gradient) of the polymer films by
altering the areas of light irradiation. It is also adaptable to large area
grafting with an ultra-small amount of monomer solution (a thin monomer solution
layer).
PMID- 28706652
TI - A catalytic chiral gel microfluidic reactor assembled via dynamic covalent
chemistry.
AB - A novel dynamic covalent gel strategy is reported to immobilize an asymmetric
catalyst within the channels of a microfluidic flow reactor. A layer of a
catalytically active Mn-salen dynamic covalent imine gel matrix was coated onto a
functionalized capillary. Mn-salen active moiety was incorporated into dynamic
covalent imine gel matrix via the reaction of a chiral Mn-salen dialdehyde unit
with a tetraamine linker. The catalytic activity of the capillary reactor has
been demonstrated in enantioselective kinetic resolution of secondary alcohols.
PMID- 28706653
TI - Successive light-induced two electron transfers in a Ru-Fe supramolecular
assembly: from Ru-Fe(ii)-OH2 to Ru-Fe(iv)-oxo.
AB - In the present work we describe the synthesis and study of a RuII-FeII
chromophore-catalyst assembly designed to perform the light-induced activation of
an iron bound water molecule and subsequent photo-driven oxidation of a
substrate. Using a series of spectroscopic techniques, we demonstrate that
excitation of the chromophore unit with 450 nm light, in the presence of a
sacrificial electron acceptor, triggers a cascade of electron transfers leading
to the formation of a high valent iron(iv)-oxo center from an iron(ii)-bound
water molecule. The activity of this catalytic center is illustrated by the
oxidation of triphenyl phosphine.
PMID- 28706654
TI - Engineering a FRET strategy to achieve a ratiometric two-photon fluorescence
response with a large emission shift and its application to fluorescence imaging.
AB - Two-photon excitation (TPE) probe-based fluorescence imaging has become one of
the most attractive diagnostic techniques to investigate biomolecules and
biological events in live cells and tissues. At the current stage most of the TPE
based sensing is reflected by fluorescence intensity changes. Nevertheless the
mere altering of intensity could be facilely affected by ambient conditions. On
the other hand, TPE probes based on an intramolecular charge transfer (ICT)
strategy could solve this problem to some extent with a morphology change-induced
emission shift. However their applications are yet constrained due to the
inherent limitation of ICT, e.g. the high degree of overlap of two emissions
bands and shifts of the TPE maxima. To achieve the desired TPE-based sensing and
to circumvent the problems stated above, we adapted a Forster resonance energy
transfer (FRET) strategy to develop small molecule ratiometric TPE fluorescent
probes. Our FRET-based ratiometric TPE fluorescent probe displays a remarkable
emission shift (up to 125 nm) with two well-resolved emission bands. Hence the
ratio of these two emission bands could enable the measurement of fluorescence
changes more accurately, thus further improving imaging in live cells and deep
tissues. To the best of our knowledge, the current reported probe has the largest
emission shift among all the small molecule ratiometric TPE fluorescent probes
while the maximum TPE wavelength remains unchanged. This work has provided a FRET
approach to fabricate novel small molecule ratiometric TPE fluorescent probes
that improve imaging in deep tissues.
PMID- 28706655
TI - Unravelling the correlation between metal induced aggregation and cellular
uptake/subcellular localization of Znsalen: an overlooked rule for design of
luminescent metal probes.
AB - Unravelling the unique effects of metal coordination on biological behaviours is
of importance to design metal based therapeutic and diagnostic agents. In this
work, we chose luminescent Znsalen (ZnL1 ) as a case study to demonstrate that
metal induced aggregation arising from the intermolecular Zn...O interaction
influences its cellular uptake and subcellular localization. Comparative studies
with the free bases (L1 and L2 ) show that ZnL1 undergoes cellular uptake through
caveolae-mediated endocytosis and internalizes in endosomal/lysosomal
compartments, in contrast to the localization of L1 and L2 in the mitochondria.
Further studies of photophysical properties, TEM imaging and DLS analysis suggest
that ZnL1 tends to form large sized fibrous structures in aqueous media. To
investigate the relationship between ZnL1 aggregation and the biological
behaviour, we used pyridine to tune the "aggregation-to-deaggregation" transition
and found that, in the presence of pyridine, ZnL1 could localize in the
mitochondria and internalize into cells through the passive diffusion pathway.
Such distinctive biological behaviours resulting from the different Znsalen
species clearly point out the importance of metal induced aggregation or metal
speciation analysis in designing metal complexes as biological probes.
PMID- 28706656
TI - Rapid water oxidation electrocatalysis by a ruthenium complex of the tripodal
ligand tris(2-pyridyl)phosphine oxide.
AB - The tris(2-pyridyl)phosphine oxide (Py3PO) complex [Ru(Py3PO)(bpy)(OH2)]2+ (bpy
is 2,2'-bipyridine) is a pH-dependent water oxidation electrocatalyst that
accelerates dramatically with increasing pH-up to 780 s-1 at pH 10 (~1 V
overpotential). Despite retaining the pentakis(pyridine) ligand arrangement
common to previously reported catalysts, the tripodal Py3PO ligand framework
supports much faster electrocatalysis. The early stages of the catalytic cycle
are proposed to follow the typical pattern of single-site ruthenium catalysts,
with two sequential 1H+/1e- proton-coupled electron transfer (PCET) oxidations,
but the pH-dependent onset of catalysis and rapid rates are distinguishing
features of the present system.
PMID- 28706657
TI - Two-photon sensitive protecting groups operating via intramolecular electron
transfer: uncaging of GABA and tryptophan.
AB - Improved photo-labile protecting groups, with high sensitivity to two-photon
excitation, are needed for the controlled release of drugs, as tools in
neuroscience and physiology. Here we present a new modular approach to the design
of caging groups based on photoinduced electron transfer from an electron-rich
two-photon dye to an electron acceptor, followed by scission of an ester to
release a carboxylic acid. Three different electron acceptors were tested:
nitrobenzyl, phenacyl and pyridinium. The nitrobenzyl system was ineffective,
giving only photochemical decomposition and no release of the carboxylic acid.
The phenacyl system also performed poorly, liberating the carboxylic acid in 20%
chemical yield and 0.2% photochemical yield. The pyridinium system was most
successful, and was tested for the release of two carboxylic acids: gamma-amino
butyric acid (GABA) and tryptophan. The caged GABA undergoes photochemical
cleavage with a chemical yield of >95% and a photochemical yield of 1%; it
exhibits a two-photon absorption cross section of 1100 GM at 700 nm,
corresponding to a two-photon uncaging cross section of 10 +/- 3 GM.
PMID- 28706658
TI - Copper doped ceria porous nanostructures towards a highly efficient bifunctional
catalyst for carbon monoxide and nitric oxide elimination.
AB - Copper doped ceria porous nanostructures with a tunable BET surface area were
prepared using an efficient and general metal-organic-framework-driven, self
template route. The XRD, SEM and TEM results indicate that Cu2+ was successfully
substituted into the CeO2 lattice and well dispersed in the CeO2:Cu2+
nanocrystals. The CeO2:Cu2+ nanocrystals exhibit a superior bifunctional
catalytic performance for CO oxidation and selective catalytic reduction of NO.
Interestingly, CO oxidation reactivity over the CeO2:Cu2+ nanocrystals was found
to be dependent on the Cu2+ dopants and BET surface area. By tuning the content
of Cu2+ and BET surface area through choosing different organic ligands, the 100%
conversion temperature of CO over CeO2:Cu2+ nanocrystals obtained from
thermolysis of CeCu-BPDC nanocrystals can be decreased to 110 degrees C. The
porous nanomaterials show a high CO conversion rate without any loss in activity
even after five cycles. Furthermore, the activity of the catalysts for NO
reduction increased with the increase of BET surface, which is in accordance with
the results of CO oxidation.
PMID- 28706659
TI - Template- and surfactant-free synthesis of ultrathin CeO2 nanowires in a mixed
solvent and their superior adsorption capability for water treatment.
AB - Ultrathin CeO2 nanowires with a diameter of 5 nm and an aspect ratio of more than
100 can be prepared by a one-step refluxing approach in a mixed solvent composed
of water and ethanol without using any templates or surfactants. The formation
mechanism of the as-synthesized ultrathin nanowires has been investigated. The as
synthesized CeO2 nanowires with a high surface area of 125.31 m2 g-1 exhibited
excellent wastewater treatment performance with high removal capacities towards
organic dyes and heavy metal ions. In addition, the as-synthesized CeO2 nanowires
can adsorb Congo red selectively from a mixed solution composed of several dyes.
Successful access to high quality ultrathin nanowires will make it possible for
their potential application in catalysis and other fields.
PMID- 28706660
TI - Turning it off! Disfavouring hydrogen evolution to enhance selectivity for CO
production during homogeneous CO2 reduction by cobalt-terpyridine complexes.
AB - Understanding the activity and selectivity of molecular catalysts for CO2
reduction to fuels is an important scientific endeavour in addressing the growing
global energy demand. Cobalt-terpyridine compounds have been shown to be
catalysts for CO2 reduction to CO while simultaneously producing H2 from the
requisite proton source. To investigate the parameters governing the competition
for H+ reduction versus CO2 reduction, the cobalt bisterpyridine class of
compounds is first evaluated as H+ reduction catalysts. We report that electronic
tuning of the ancillary ligand sphere can result in a wide range of second-order
rate constants for H+ reduction. When this class of compounds is next submitted
to CO2 reduction conditions, a trend is found in which the less active catalysts
for H+ reduction are the more selective towards CO2 reduction to CO. This
represents the first report of the selectivity of a molecular system for CO2
reduction being controlled through turning off one of the competing reactions.
The activities of the series of catalysts are evaluated through foot-of-the-wave
analysis and a catalytic Tafel plot is provided.
PMID- 28706661
TI - Controlled levels of protein modification through a chromatography-mediated
bioconjugation.
AB - Synthetically modified proteins are increasingly finding applications as well
defined scaffolds for materials. In practice it remains difficult to construct
bioconjugates with precise levels of modification because of the limited number
of repeated functional groups on proteins. This article describes a method to
control the level of protein modification in cases where there exist multiple
potential modification sites. A protein is first tagged with a handle using any
of a variety of modification chemistries. This handle is used to isolate proteins
with a particular number of modifications via affinity chromatography, and then
the handle is elaborated with a desired moiety using an oxidative coupling
reaction. This method results in a sample of protein with a well-defined number
of modifications, and we find it particularly applicable to systems like protein
homomultimers in which there is no way to discern between chemically identical
subunits. We demonstrate the use of this method in the construction of a protein
templated light-harvesting mimic, a type of system which has historically been
difficult to make in a well-defined manner.
PMID- 28706662
TI - Sulfonyl fluorides as privileged warheads in chemical biology.
AB - Sulfonyl fluoride electrophiles have found significant utility as reactive probes
in chemical biology and molecular pharmacology. As warheads they possess the
right balance of biocompatibility (including aqueous stability) and protein
reactivity. Their functionality is privileged in this regard as they are known to
modify not only reactive serines (resulting in their common use as protease
inhibitors), but also context-specific threonine, lysine, tyrosine, cysteine and
histidine residues. This review describes the application of sulfonyl fluoride
probes across various areas of research and explores new approaches that could
further enhance the chemical biology toolkit. We believe that sulfonyl fluoride
probes will find greater utility in areas such as covalent enzyme inhibition,
target identification and validation, and the mapping of enzyme binding sites,
substrates and protein-protein interactions.
PMID- 28706663
TI - Charging and discharging at the nanoscale: Fermi level equilibration of metallic
nanoparticles.
AB - The redox properties of metallic nanoparticles are discussed, in particular the
relationships between excess charge, size and the Fermi level of the electrons.
The redox potentials are derived using simple electrostatic models to provide a
straightforward understanding of the basic phenomena. The different techniques
used to measure the variation of Fermi level are presented. Finally, redox
aspects of processes such as toxicity, electrochromicity and surface plasmon
spectroscopy are discussed.
PMID- 28706664
TI - Probing plasmonic nanostructures by photons and electrons.
AB - We discuss recent developments for studying plasmonic metal nanostructures.
Exploiting photons and electrons opens up new capabilities to probe the complete
plasmon spectrum including bright and dark modes and related local optical fields
at subnanometer spatial resolution. This comprehensive characterization of
plasmonic properties of metal nanostructures provides new basic insight into the
fundamental physics of "surface enhanced" spectroscopy in hottest hot spots and
enables us to optimize plasmon supported processes and devices.
PMID- 28706665
TI - Mechanism and selectivity of the dinuclear iron benzoyl-coenzyme A epoxidase
BoxB.
AB - Benzoyl-CoA epoxidase is a dinuclear iron enzyme that catalyzes the epoxidation
reaction of the aromatic ring of benzoyl-CoA with chemo-, regio- and stereo
selectivity. It has been suggested that this enzyme may also catalyze the
deoxygenation reaction of epoxide, suggesting a unique bifunctionality among the
diiron enzymes. We report a density functional theory study of this enzyme aimed
at elucidating its mechanism and the various selectivities. The epoxidation is
suggested to start with the binding of the O2 molecule to the diferrous center to
generate a diferric peroxide complex, followed by concerted O-O bond cleavage and
epoxide formation. Two different pathways have been located, leading to (2S,3R)
epoxy and (2R,3S)-epoxy products, with barriers of 17.6 and 20.4 kcal mol-1,
respectively. The barrier difference is 2.8 kcal mol-1, corresponding to a
diastereomeric excess of about 99 : 1. Further isomerization from epoxide to
phenol is found to have quite a high barrier, which cannot compete with the
product release step. After product release into solution, fast epoxide-oxepin
isomerization and racemization can take place easily, leading to a racemic
mixture of (2S,3R) and (2R,3S) products. The deoxygenation of epoxide to
regenerate benzoyl-CoA by a diferrous form of the enzyme proceeds via a stepwise
mechanism. The C2-O bond cleavage happens first, coupled with one electron
transfer from one iron center to the substrate, to form a radical intermediate,
which is followed by the second C3-O bond cleavage. The first step is rate
limiting with a barrier of only 10.8 kcal mol-1. Further experimental studies are
encouraged to verify our results.
PMID- 28706666
TI - Virtual screening for high affinity guests for synthetic supramolecular
receptors.
AB - The protein/ligand docking software GOLD, which was originally developed for drug
discovery, has been used in a virtual screen to identify small molecules that
bind with extremely high affinities (K ~ 107 M-1) in the cavity of a cubic
coordination cage in water. A scoring function was developed using known guests
as a training set and modified by introducing an additional term to take account
of loss of guest flexibility on binding. This scoring function was then used in
GOLD to successfully identify 15 new guests and accurately predict the binding
constants. This approach provides a powerful predictive tool for virtual
screening of large compound libraries to identify new guests for synthetic hosts,
thereby greatly simplifying and accelerating the process of identifying guests by
removing the reliance on experimental trial-and-error.
PMID- 28706667
TI - In vivo evaluation of small-molecule thermoresponsive anticancer drugs
potentiated by hyperthermia.
AB - Hyperthermia used as an adjuvant with chemotherapy is highly promising in the
treatment of certain cancers. Currently, the small molecule drugs used in
combination with hyperthermia were not designed for this application. Herein, we
report the evaluation of a chlorambucil and a ruthenium compound modified with a
long fluorous chain, which exhibit thermoresponsive activity in colorectal
adenocarcinoma xenografts in athymic mice in combination with mild hyperthermia
(42 degrees C). Intraperitoneal injection of the derivatives followed by local
hyperthermia showed a synergistic tumor growth reduction by 79% and 90% for the
chlorambucil and ruthenium-based derivatives, respectively, with the latter
exhibiting a higher synergy in combination with hyperthermia compared to the
monotherapies. Histological analysis shows that both derivatives in combination
with hyperthermia significantly decrease the number of proliferating tumor cells.
PMID- 28706668
TI - Molecular glues for manipulating enzymes: trypsin inhibition by benzamidine
conjugated molecular glues.
AB - Water-soluble bioadhesive polymers bearing multiple guanidinium ion (Gu+)
pendants at their side-chain termini (Glue n -BA, n = 10 and 29) that were
conjugated with benzamidine (BA) as a trypsin inhibitor were developed. The Glue
n -BA molecules are supposed to adhere to oxyanionic regions of the trypsin
surface, even in buffer, via a multivalent Gu+/oxyanion salt-bridge interaction,
such that their BA group properly blocks the substrate-binding site. In fact,
Glue10-BA and Glue29-BA exhibited 35- and 200-fold higher affinities for trypsin,
respectively, than a BA derivative without the glue moiety (TEG-BA). Most
importantly, Glue10-BA inhibited the protease activity of trypsin 13-fold more
than TEG-BA. In sharp contrast, m Glue27-BA, which bears 27 Gu+ units along the
main chain and has a 5-fold higher affinity than TEG-BA for trypsin, was inferior
even to TEG-BA for trypsin inhibition.
PMID- 28706669
TI - Chemical assay-guided natural product isolation via solid-supported
chemodosimetric fluorescent probe.
AB - As a new model of chemical assay-guided natural product isolation, an effective
chemodosimetric assay system was devised. Our chemical assay system features a
fluorogenic chemodosimeter immobilized on a solid support, which offers
advantages in identifying the desired compounds in complex natural product
mixtures. To isolate only compounds with the target functional groups, the click
chemistry concept was adopted. The model system presented here was developed for
natural products with a terminal alkyne. Using our newly designed alkyne sensing
beads with the aforementioned features, we have readily identified, quantified,
and isolated compounds with a terminal alkyne group from plant extracts.
PMID- 28706670
TI - Computational discovery and experimental verification of tyrosine kinase
inhibitor pazopanib for the reversal of memory and cognitive deficits in rat
model neurodegeneration.
AB - Cognition and memory impairment are hallmarks of the pathological cascade of
various neurodegenerative disorders. Herein, we developed a novel computational
strategy with two-dimensional virtual screening for not only affinity but also
specificity. We integrated the two-dimensional virtual screening with ligand
screening for 3D shape, electrostatic similarity and local binding site
similarity to find existing drugs that may reduce the signs of cognitive
deficits. For the first time, we found that pazopanib, a tyrosine kinase
inhibitor marketed for cancer treatment, inhibits acetylcholinesterase (AchE)
activities at sub-micromolar concentration. We evaluated and compared the effects
of intragastrically-administered pazopanib with donepezil, a marketed AchE
inhibitor, in cognitive and behavioral assays including the novel object
recognition test, Y maze and Morris water maze test. Surprisingly, we found that
pazopanib can restore memory loss and cognitive dysfunction to a similar extent
as donepezil in a dosage of 15 mg kg-1, only one fifth of the equivalent clinical
dosage for cancer treatment. Furthermore, we demonstrated that pazopanib
dramatically enhances the hippocampal Ach levels and increases the expression of
the synaptic marker SYP. These findings suggest that pazopanib may become a
viable treatment option for memory and cognitive deficits with a good safety
profile in humans.
PMID- 28706671
TI - Highly stable and reusable imprinted artificial antibody used for in situ
detection and disinfection of pathogens.
AB - Sandwich ELISA methods have been widely used for biomarker and pathogen detection
because of their high specificity and sensitivity. However, the main drawbacks of
this assay are the cost, the time-consuming procedure for the isolation of
antibodies and their poor stability. To overcome these restrictions, we herein
fabricated artificial antibodies based on imprinting technology and developed a
sandwich ELISA for pathogen detection. Both the capture and detection antibodies
were obtained via an in situ method, with simplicity, rapidity and low cost. The
peroxidase mimics, the CeO2 nanoparticles, as signal generators were integrated
with the detection antibody. The fabricated artificial antibodies exhibited not
only natural antibody-like binding affinities and selectivities, but also
superior stability and reusability. The detection limit was about 500 CFU mL-1,
which is much lower than that of traditional ELISA methods (104 to 105 CFU mL-1).
Furthermore, the capture antibody can disinfect pathogens in situ.
PMID- 28706672
TI - Bis(dipyrrinato)metal(ii) coordination polymers: crystallization, exfoliation
into single wires, and electric conversion ability.
AB - One-dimensional coordination polymers (1D-CPs) tend either to dissociate into
constitutive ligands and metals readily in solution, or to aggregate randomly and
amorphously, which prevents them from widespread application. In the present
research, 1D-CPs comprising bridging dipyrrin ligands and divalent metal ions
(Zn2+, Ni2+, and Cu2+) are synthesized. A liquid/liquid interfacial reaction
gives rise to single crystals suitable for X-ray diffraction analysis: A
dichloromethane solution of the ligand is layered with aqueous metal(ii) acetate,
such that the coordination reaction proceeds at the liquid/liquid interface.
Isolated single fibers of the zinc coordination polymer may be exfoliated from
the single crystal or bulk solid upon ultrasonication. Atomic force microscopy
(AFM) detects the isolated fibers with lengths of more than several MUm. The
exfoliated 1D-CP wires feature good processability, realizing a conjugate with
single-wall carbon nanotubes (SWCNTs), and a thin film on a transparent SnO2
electrode. The processed materials show electric conversion ability: For example,
the modified SnO2 electrode serves as a photoanode for a photoelectric conversion
system. The designability and tunability of the present 1D-CPs is demonstrated by
a ligand modification, affording a luminescent property and an extension of the
photoelectric conversion response to longer wavelengths.
PMID- 28706673
TI - A hybrid living/organic electrochemical transistor based on the Physarum
polycephalum cell endowed with both sensing and memristive properties.
AB - A hybrid bio-organic electrochemical transistor was developed by interfacing an
organic semiconductor, poly(3,4-ethylenedioxythiophene) doped with poly(styrene
sulfonate), with the Physarum polycephalum cell. The system shows unprecedented
performances since it could be operated both as a transistor, in a three-terminal
configuration, and as a memristive device in a two terminal configuration mode.
This is quite a remarkable achievement since, in the transistor mode, it can be
used as a very sensitive bio-sensor directly monitoring biochemical processes
occurring in the cell, while, as a memristive device, it represents one of the
very first examples of a bio-hybrid system demonstrating such a property. Our
system combines memory and sensing in the same system, possibly interfacing
unconventional computing. The system was studied by a full electrical
characterization using a series of different gate electrodes, namely made of Ag,
Au and Pt, which typically show different operation modes in organic
electrochemical transistors. Our experiment demonstrates that a remarkable
sensing capability could potentially be implemented. We envisage that this system
could be classified as a Bio-Organic Sensing/Memristive Device (BOSMD), where the
dual functionality allows merging of the sensing and memory properties, paving
the way to new and unexplored opportunities in bioelectronics.
PMID- 28706674
TI - Single graphene nanoplatelets: capacitance, potential of zero charge and
diffusion coefficient.
AB - Nano-impact chronoamperometric experiments are a powerful technique for
simultaneously probing both the potential of zero charge (PZC) and the diffusion
coefficient (D0) of graphene nanoplatelets (GNPs). The method provides an
efficient general approach to material characterisation. Using nano-impact
experiments, capacitative impacts can be seen for graphene nanoplatelets of 15
MUm width and 6-8 nm thickness. The current transient features seen allow the
determination of the PZC of the graphene nanoplatelet in PBS buffer as -0.14 +/-
0.03 V (vs. saturated calomel electrode). The diffusion coefficient in the same
aqueous medium, isotonic with many biological conditions, for the graphene
nanoplatelets is experimentally found to be 2 +/- 0.8 * 10-13 m2 s-1. This quick
characterisation technique may significantly assist the application of graphene
nanoplatelets, or similar nano-materials, in electronic, sensor, and clinical
medicinal technologies.
PMID- 28706675
TI - Methyl viologen-templated zinc gallophosphate zeolitic material with dual photo
/thermochromism and tuneable photovoltaic activity.
AB - A novel zinc gallophosphate zeolitic material
|(C12H14N2)4F1.33|[Ga13.33Zn6.67(PO4)20] (denoted as JU101) has been prepared by
using in situ generated methyl viologen (MV) as the template. The framework of
JU101 features two building units including an unprecedented fused d6r and a
novel [412.64.82.102] cavity. The connection of these two building units forms a
3D intersecting pore system containing 8-rings along the [010] direction, and 10
rings along the [001] and [100] directions. The MV-templated JU101 zeolitic
material offers a new type of electron transfer system, which endows the material
with interesting photochromism, thermochromism, and tuneable photovoltaic
activity in response to light and heating. Importantly, JU101 shows an extended
photochromism range from UV to visible light, high thermal stability, as well as
a long-lived charge-separated state for potential application in solar energy
conversion.
PMID- 28706676
TI - Direct in vivo imaging of ferrous iron dyshomeostasis in ageing Caenorhabditis
elegans.
AB - Iron is essential for eukaryotic biochemistry. Systematic trafficking and storage
is required to maintain supply of iron while preventing it from catalysing
unwanted reactions, particularly the generation of oxidising reactive species.
Iron dyshomeostasis has been implicated in major age-associated diseases
including cancers, neurodegeneration and heart disease. Here, we employ
population-level X-ray fluorescence imaging and native-metalloproteomic analysis
to determine that altered iron coordination and distribution is a pathological
imperative of ageing in the nematode, Caenorhabditis elegans. Our approach
provides a method to simultaneously study iron metabolism across different scales
of biological organisation, from populations to cells. Here we report how and
where iron homeostasis is lost during C. elegans ageing, and its relationship to
the age-related elevation of damaging reactive oxygen species. We find that wild
types utilise ferritin to sustain longevity, buffering against exogenous iron and
showing rapid ageing if ferritin is ablated. After reproduction, escape of iron
from safe-storage in ferritin raised cellular Fe2+ load in the ageing C. elegans,
and increased generation of reactive species. These findings support the
hypothesis that iron-mediated processes drive senescence. We propose that loss of
iron homeostasis may be a fundamental and inescapable consequence of ageing that
could represent a critical target for therapeutic strategies to improve health
outcomes in ageing.
PMID- 28706677
TI - Reaction-based Indicator displacement Assay (RIA) for the selective colorimetric
and fluorometric detection of peroxynitrite.
AB - Using the self-assembly of aromatic boronic acids with Alizarin Red S (ARS), we
developed a new chemosensor for the selective detection of peroxynitrite.
Phenylboronic acid (PBA), benzoboroxole (BBA) and 2-(N,N
dimethylaminomethyl)phenylboronic acid (NBA) were employed to bind with ARS to
form the complex probes. In particular, the ARS-NBA system with a high binding
affinity can preferably react with peroxynitrite over hydrogen peroxide and other
ROS/RNS due to the protection of the boron via the solvent-insertion B-N
interaction. Our simple system produces a visible colorimetric change and on-off
fluorescence response towards peroxynitrite. By coupling a chemical reaction that
leads to an indicator displacement, we have developed a new sensing strategy,
referred to herein as RIA (Reaction-based Indicator displacement Assay).
PMID- 28706678
TI - Expanding discriminative dimensions for analysis and imaging.
AB - Eliminating the contribution of interfering compounds is a key step in chemical
analysis. In complex media, one possible approach is to perform a preliminary
separation. However purification is often demanding, long, and costly; it may
also considerably alter the properties of interacting components of the mixture
(e.g. in a living cell). Hence there is a strong interest for developing
separation-free non-invasive analytical protocols. Using photoswitchable probes
as labelling and titration contrast agents, we demonstrate that the association
of a modulated monochromatic light excitation with a kinetic filtering of the
overall observable is much more attractive than constant excitation to read-out
the contribution from a target probe under adverse conditions. An extensive
theoretical framework enabled us to optimize the out-of-phase concentration first
order response of a photoswitchable probe to modulated illumination by
appropriately matching the average light intensity and the radial frequency of
the light modulation to the probe dynamics. Thus, we can selectively and
quantitatively extract from an overall signal the contribution from a target
photoswitchable probe within a mixture of species, photoswitchable or not. This
simple titration strategy is more specifically developed in the context of
fluorescence imaging, which offers promising perspectives.
PMID- 28706679
TI - Hollow ternary PtPdCu nanoparticles: a superior and durable cathodic
electrocatalyst.
AB - Hollow alloyed nanoparticles (NPs) represent one kind of promising fuel cell
electrocatalyst. However, the formation of single-cavity hollow structures by a
dealloying process is quite challenging owing to the random leaching/dissolution
of transition metals, surface passivation and the limited diffusion distance of
the noble metals. Here we present a facile method to prepare hollow PtPdCu NPs
derived from monodisperse alloy NPs by an acetic acid-assisted dealloying
process. Here, acetic acid not only acts as a chemical etching agent but also
plays an important role in the removal of the residual surfactants for colloidal
NPs. Our findings rectify the current knowledge that hollow alloyed NPs cannot be
prepared by a dealloying strategy and provide further understanding of the
dealloying process in a ternary system. Such unique hollow ternary PtPdCu NPs
exhibit outstanding durability and improved catalytic activity toward the oxygen
reduction reaction.
PMID- 28706680
TI - Induction of targeted necrosis with HER2-targeted platinum(iv) anticancer
prodrugs.
AB - It is well-recognized that the failure of many chemotherapeutics arises due to an
inability to induce apoptosis. Most cancers acquire a myriad of pro-survival
adaptations, and the vast heterogeneity and accumulation of multiple often
unrelated anti-apoptotic signaling pathways have been a major stumbling block
towards the development of conventional chemotherapeutics, which can overcome
drug resistance. We have developed highly potent and selective HER2-targeted
Pt(iv) prodrugs bearing anti-HER2/neu peptides that induce targeted necrosis as a
novel strategy to circumvent apoptosis-resistance. These Pt(iv)-peptide
conjugates exhibit a unique biphasic mode of cytotoxicity comprising rapid
killing of cancer cells via necrosis in the first phase followed by an extended
and gradual phase of delayed cell death. We demonstrate that these Pt(iv)-peptide
prodrugs are more potent than their Pt(ii) congeners in direct cell-killing and
exhibit comparable long-term inhibition of proliferative capacity and with
greater selectivity against HER2-positive cancer cells.
PMID- 28706681
TI - Unexpected effect of catalyst concentration on photochemical CO2 reduction by
trans(Cl)-Ru(bpy)(CO)2Cl2: new mechanistic insight into the CO/HCOO- selectivity.
AB - Photochemical CO2 reduction catalysed by trans(Cl)-Ru(bpy)(CO)2Cl2 (bpy = 2,2'
bipyridine) efficiently produces carbon monoxide (CO) and formate (HCOO-) in N,N
dimethylacetamide (DMA)/water containing [Ru(bpy)3]2+ as a photosensitizer and 1
benzyl-1,4-dihydronicotinamide (BNAH) as an electron donor. We have unexpectedly
found catalyst concentration dependence of the product ratio (CO/HCOO-) in the
photochemical CO2 reduction: the ratio of CO/HCOO- decreases with increasing
catalyst concentration. The result has led us to propose a new mechanism in which
HCOO- is selectively produced by the formation of a Ru(i)-Ru(i) dimer as the
catalyst intermediate. This reaction mechanism predicts that the Ru-Ru bond
dissociates in the reaction of the dimer with CO2, and that the insufficient
electron supply to the catalyst results in the dominant formation of HCOO-. The
proposed mechanism is supported by the result that the time-course profiles of CO
and HCOO- in the photochemical CO2 reduction catalysed by [Ru(bpy)(CO)2Cl]2 (0.05
mM) are very similar to those of the reduction catalysed by trans(Cl)
Ru(bpy)(CO)2Cl2 (0.10 mM), and that HCOO- formation becomes dominant under low
intensity light. The kinetic analyses based on the proposed mechanism could
excellently reproduce the unusual catalyst concentration effect on the product
ratio. The catalyst concentration effect observed in the photochemical CO2
reduction using [Ru(4dmbpy)3]2+ (4dmbpy = 4,4'-dimethyl-2,2'-bipyridine) instead
of [Ru(bpy)3]2+ as the photosensitizer is also explained with the kinetic
analyses, reflecting the smaller quenching rate constant of excited
[Ru(4dmbpy)3]2+ by BNAH than that of excited [Ru(bpy)3]2+. We have further
synthesized trans(Cl)-Ru(6Mes-bpy)(CO)2Cl2 (6Mes-bpy = 6,6'-dimesityl-2,2'
bipyridine), which bears bulky substituents at the 6,6'-positions in the 2,2'
bipyridyl ligand, so that the ruthenium complex cannot form the dimer due to the
steric hindrance. We have found that this ruthenium complex selectively produces
CO, which strongly supports the catalytic mechanism proposed in this work.
PMID- 28706682
TI - Versatile control of the submolecular motion of di(acylamino)pyridine-based
[2]rotaxanes.
AB - A cyclic network of chemical reactions has been conceived for exchanging the
dynamic behaviour of di(acylamino)pyridine-based rotaxanes and surrogates. X-ray
diffraction studies revealed the intercomponent interactions in these interlocked
compounds and were consistent with those found in solution by dynamic NMR
experiments. This particular binding site was incorporated into a molecular
shuttle enabled for accessing two states with an outstanding positional
discrimination through chemical manipulation. Furthermore, the ability of the
di(acylamino)pyridine domain to associate with external binders with a
complementary array of HB donor and acceptor sites was exploited for the advance
of an unprecedented electrochemical switch operating through a reversible anion
radical recognition process.
PMID- 28706683
TI - Slow magnetic relaxation in a novel carboxylate/oxalate/hydroxyl bridged
dysprosium layer.
AB - A new 2D dysprosium layer compound has been successfully synthesized from
reaction with 2-(3-pyridyl) pyrimidine-4-carboxylic acid (H3-py-4-pmc), in which
the Dy3+ ions reside in square antiprismatic coordination environments and are
connected by carboxylate/oxalate/hydroxyl bridges. Magnetic studies reveal
ferromagnetic interactions between Dy3+ ions, slow magnetic relaxation with an
effective energy barrier Ueff of 186 K under zero dc field and pronounced
hysteresis loops at low temperatures. Further dilution magnetic study suggests
that the slow magnetic relaxation originates from the single-ion magnetic
behavior of Dy3+ ion and that magnetic coupling suppresses the quantum tunneling
of magnetization at low temperature. In addition, theoretical calculation
indicates strong Ising anisotropy of the Dy3+ ion that is due to the strong
interaction between Dy3+ ions and hydroxyl groups.
PMID- 28706684
TI - Development of zinc alkyl/air systems as radical initiators for organic
reactions.
AB - This paper reports a series of comparative experiments on the activity of carbon-
and oxygen-centred radical species in a model reaction of the radical addition of
THF to imines mediated by a series of zinc alkyl/air reaction systems. The study
strongly contradicts the notion that generally R radicals are the initiating
species in organic reactions mediated by R n M/air systems, and simultaneously
demonstrates that oxygen-centred radical species are the key intermediates
responsible for the initiation process. In addition, a new efficient RZn(L)/air
initiating system for radical organic reactions exampled by a model reaction of
radical addition of THF to imines is developed. Moreover, the isolation and
structural characterization of the first zinc alkylperoxide supported by a
carboxylate ligand, [Zn4(MU3-OOtBu)3(MU4-O)(O2CEt)3]2, as well as the novel
octanuclear zinc oxo(alkoxide) aggregate with entrapped O-THF species, [Zn4(MU4
O)(MU3-2-O-THF)(O2CEt)5]2, provide clear mechanistic signatures for the mode of
function of the RZn(O2CR')/air system.
PMID- 28706685
TI - Discovery of a novel ligand that modulates the protein-protein interactions of
the AAA+ superfamily oncoprotein reptin.
AB - Developing approaches to discover protein-protein interactions (PPIs) remains a
fundamental challenge. A chemical biology platform is applied here to identify
novel PPIs for the AAA+ superfamily oncoprotein reptin. An in silico screen
coupled with chemical optimization provided Liddean, a nucleotide-mimetic which
modulates reptin's oligomerization status, protein-binding activity and global
conformation. Combinatorial peptide phage library screening of Liddean-bound
reptin with next generation sequencing identified interaction motifs including a
novel reptin docking site on the p53 tumor suppressor protein. Proximity ligation
assays demonstrated that endogenous reptin forms a predominantly cytoplasmic
complex with its paralog pontin in cancer cells and Liddean promotes a shift of
this complex to the nucleus. An emerging view of PPIs in higher eukaryotes is
that they occur through a striking diversity of linear peptide motifs. The
discovery of a compound that alters reptin's protein interaction landscape
potentially leads to novel avenues for therapeutic development.
PMID- 28706686
TI - Cr(i)Cl as well as Cr+ are stabilised between two cyclic alkyl amino carbenes.
AB - Cr(i)Cl is a very unstable species. The present work describes the stabilisation
of Cr(i)Cl in the low coordinate environment of cyclic alkyl(amino) carbene
ligands and its synthetic application to yield an unprecedented cationic complex
with a two coordinate Cr(i). One electron reduction of (cAAC)2CrCl2 (1) with
equivalent amount of KC8 results in the formation of (cAAC)2CrCl (2), with a
distorted trigonal planar configuration at the metal centre. SQUID, EPR and
theoretical studies reveal a Cr(i) centre with S = 5/2 spin ground state for 2.
It represents the first example of a mononuclear Cr complex showing slow
relaxation of magnetisation under an applied magnetic field. The chlorine atom in
2 is expected to be prone to further reactions with appropriate reagents. This
qualifies 2 as a promising precursor for the preparation of various interesting
complexes with Cr(i) in a low coordinate environment. The first example of this
metathesis reaction is observed when 2 is treated with Na[B(C6H3(CF3)2)4]
resulting in [(cAAC)2Cr]+[B(C6H3(CF3)2)4]-, a linear cationic complex with two
coordinate Cr(i) and an S = 5/2 spin ground state.
PMID- 28706687
TI - Two more pieces of the colibactin genotoxin puzzle from Escherichia coli show
incorporation of an unusual 1-aminocyclopropanecarboxylic acid moiety.
AB - Colibactin represents a structurally undefined class of bacterial genotoxin
inducing DNA damage and genomic instability in mammalian cells, thus promoting
tumour development and exacerbating lymphopenia in animal models. The colibactin
biosynthetic gene cluster (clb) has been known for ten years and it encodes a
hybrid nonribosomal peptide synthetase (NRPS)/polyketide synthase (PKS) assembly
line. Nevertheless, the final chemical product(s) remain unknown. Previously, we
and others reported several colibactin pathway-related metabolites including N
myristoyl-d-asparagine (1) as part of a prodrug precursor that is cleaved from
the putative precolibactin to form active colibactin by the peptidase ClbP.
Herein, we report two new colibactin pathway-related metabolites (2 and 3)
isolated from a clbP mutant of the probiotic E. coli Nissle 1917 strain. Their
structures were established by HRMS and NMR. Compound 2 shows an additional 4
aminopenatanoic acid moiety with respect to 1, while 3 is characterized by the
presence of an unusual 7-methyl-4-azaspiro[2.4]hept-6-en-5-one residue. Moreover,
we propose the biosynthetic pathway towards both intermediates on the basis of
extensive gene inactivation and feeding experiments. The identification of 2 and
3 provides further insight into colibactin biosynthesis including the involvement
and formation of a rare 1-aminocyclopropanecarboxylic acid unit. Thus, our work
establishes additional steps of the pathway forming the bacterial genotoxin
colibactin.
PMID- 28706688
TI - Effect of phenolic glycolipids from Mycobacterium kansasii on proinflammatory
cytokine release. A structure-activity relationship study.
AB - The cell wall of pathogenic mycobacteria is abundant with virulence factors,
among which phenolic glycolipids (PGLs) are prominent examples. Mycobacterium
kansasii, an important opportunistic pathogen, produces seven PGLs and their
effect on the release of important proinflammatory cytokines that mediate disease
progression has not been investigated. We previously showed that proinflammatory
cytokines are modulated by PGLs from M. tuberculosis, M. leprae and M. bovis. In
this paper we describe the synthesis of a series of 17 analogs of M. kansasii
PGLs containing a truncated aglycone. Subsequently, the effect of these compounds
on the release of proinflammatory cytokines (TNF-alpha, IL-6, IL-1beta, MCP-1)
and nitric oxide (NO) was evaluated. These compounds exerted an immunoinhibitory
effect on the release of the tested cytokines. The concentration-dependent
inhibitory profile of the tested molecules was also found to be dependent on the
methylation pattern of the molecule and was mediated via toll-like receptor (TLR)
2. This study led to the discovery of a glycolipid (18) that shows promising
potent anti-inflammatory properties making it a potential candidate for further
optimization of its anti-inflammatory profile.
PMID- 28706689
TI - Self-induced redox cycling coupled luminescence on nanopore recessed disk
multiscale bipolar electrodes.
AB - We present a new configuration for coupling fluorescence microscopy and
voltammetry using self-induced redox cycling for ultrasensitive electrochemical
measurements. An array of nanopores, each supporting a recessed disk electrode
separated by 100 nm in depth from a planar multiscale bipolar top electrode, was
fabricated using multilayer deposition, nanosphere lithography, and reactive-ion
etching. Self-induced redox cycling was induced on the disk electrode producing
~30* current amplification, which was independently confirmed by measuring
induced electrogenerated chemiluminescence from Ru(bpy)32/3+/tri-n-propylamine on
the floating bipolar electrode. In this design, redox cycling occurs between the
recessed disk and the top planar portion of a macroscopic thin film bipolar
electrode in each nanopore. Electron transfer also occurs on a remote (mm
distance) portion of the planar bipolar electrode to maintain electroneutrality.
This couples the electrochemical reactions of the target redox pair in the
nanopore array with a reporter, such as a potential-switchable fluorescent
indicator, in the cell at the distal end of the bipolar electrode. Oxidation or
reduction of reversible analytes on the disk electrodes were accompanied by
reduction or oxidation, respectively, on the nanopore portion of the bipolar
electrode and then monitored by the accompanying oxidation of dihydroresorufin or
reduction of resorufin at the remote end of the bipolar electrode, respectively.
In both cases, changes in fluorescence intensity were triggered by the reaction
of the target couple on the disk electrode, while recovery was largely governed
by diffusion of the fluorescent indicator. Reduction of 1 nM of Ru(NH3)63+ on the
nanoelectrode array was detected by monitoring the fluorescence intensity of
resorufin, demonstrating high sensitivity fluorescence-mediated electrochemical
sensing coupled to self-induced redox cycling.
PMID- 28706690
TI - Ratiometric detection of pH fluctuation in mitochondria with a new
fluorescein/cyanine hybrid sensor.
AB - The homeostasis of mitochondrial pH (pHm) is crucial in cell physiology.
Developing small-molecular fluorescent sensors for the ratiometric detection of
pHm fluctuation is highly demanded yet challenging. A ratiometric pH sensor, Mito
pH, was constructed by integrating a pH-sensitive FITC fluorophore with a pH
insensitive hemicyanine group. The hemicyanine group also acts as the
mitochondria targeting group due to its lipophilic cationic nature. Besides its
ability to target mitochondria, this sensor provides two ratiometric pH sensing
modes, the dual excitation/dual emission mode (Dex/Dem) and dual excitation (Dex)
mode, and its linear and reversible ratiometric response range from pH 6.15 to
8.38 makes this sensor suitable for the practical tracking of pHm fluctuation in
live cells. With this sensor, stimulated pHm fluctuation has been successfully
tracked in a ratiometric manner via both fluorescence imaging and flow cytometry.
PMID- 28706691
TI - Highly stable PtP alloy nanotube arrays as a catalyst for the oxygen reduction
reaction in acidic medium.
AB - Nanostructured Pt-metal alloys have shown impressive catalytic properties for the
oxygen reduction reaction (ORR) in acidic medium, but their long-term stability
has not been satisfactory. Herein, we look beyond the traditional Pt-metal alloys
and have developed a new kind of Pt-nonmetal alloy electrocatalyst for the ORR.
Specifically, the novel catalyst is composed of interconnected platinum
monophosphide (PtP) alloy nanocrystals (~3-4 nm) and featured supportless
nanotube array morphologies. Due to the unique combination of composition and
structure, the obtained PtP alloy nanotube arrays not only exhibited remarkable
ORR activity, but also showed almost no degradation of the half-wave potential
after accelerated durability tests. The result suggests that alloying Pt with a
nonmetallic element (such as P) is indeed an effective approach to address the
poor stability of Pt-based catalysts in acidic medium.
PMID- 28706692
TI - Ligand-directed dibromophenyl benzoate chemistry for rapid and selective
acylation of intracellular natural proteins.
AB - A rapid and selective ligand-directed chemical reaction was developed for the
acylation of proteins in living cells on the basis of ligand-directed chemistry.
By fine tuning the reactivity and stability of the phenyl ester derivatives, we
successfully identified ortho-dibromophenyl benzoate as the optimal reactive
motif. It was sufficiently stable in an aqueous buffer, hydrolyzing less than 10%
after 13 h of incubation, but reactive enough for efficient and selective protein
labeling in living mammalian cells, as well as in vitro (referred to as ligand
directed dibromophenyl benzoate (LDBB) chemistry). Using this chemistry, various
fluorophores can be tethered to the target protein directly, which allows
fluorescence visualization of the labeled protein in live cells using different
colored fluorophore groups (including coumarin, fluorescein and rhodamine).
Furthermore, this labeling is applicable to not only an overexpressed protein (E.
coli dihydrofolate reductase) but also endogenous human carbonic anhydrase II and
XII under living cell conditions. LDBB chemistry is a new entry of ligand
directed protein labeling methods, and should be particularly useful for the
imaging of natural proteins in living cells.
PMID- 28706693
TI - Humidity-dependent surface tension measurements of individual inorganic and
organic submicrometre liquid particles.
AB - Surface tension, an important property of liquids, is easily measured for bulk
samples. However, for droplets smaller than one micron in size, there are
currently no reported measurements. In this study, atomic force microscopy (AFM)
and force spectroscopy have been utilized to measure surface tension of
individual submicron sized droplets at ambient pressure and controlled relative
humidity (RH). Since the surface tension of atmospheric aerosols is a key factor
in understanding aerosol climate effects, three atmospherically relevant systems
(NaCl, malonic and glutaric acids) were studied. Single particle AFM measurements
were successfully implemented in measuring the surface tension of deliquesced
particles on the order of 200 to 500 nm in diameter. Deliquesced particles
continuously uptake water at high RH, which changes the concentration and surface
tension of the droplets. Therefore, surface tension as a function of RH was
measured. AFM based surface tension measurements are close to predicted values
based on bulk measurements and activities of these three chemical systems. Non
ideal behaviour in concentrated organic acid droplets is thought to be important
and the reason for differences observed between bulk solution predictions and AFM
data. Consequently, these measurements are crucial in order to improve
atmospheric climate models as direct measurements hitherto have been previously
inaccessible due to instrument limitations.
PMID- 28706694
TI - Visualizing electronic interactions between iron and carbon by X-ray chemical
imaging and spectroscopy.
AB - The electronic interaction of a catalyst and its support is of vital importance
to its catalytic performance. However, it is still a great challenge to directly
probe the interaction due to the lack of well-defined models and efficient
technical means. In this study, we report that pod-like carbon nanotubes with
encapsulated iron particles (Pod-Fe) and scanning transmission X-ray microscopy
(STXM) can be used as an ideal model and technique to study the electronic
interaction between carbon shells and iron particles. The chemical imaging and
spectroscopy of Pod-Fe by STXM show that the local electronic structures at C K
edge near edge (pi*) of carbon shells can be significantly modified by the
encapsulated iron particles, which promotes the adsorption of oxygen-containing
species, and thereby further modifies the electronic structure (pi* and sigma*)
of the carbon shells. Moreover, computed X-ray absorption near edge structure
spectra (XANES) confirmed the electronic modifications of carbon shells by the
encapsulated iron particles. The present study provides a direct evidence of
electronic interactions with simultaneously collected images and spectra, which
can promote the understanding towards the nature of active sites and supports.
PMID- 28706695
TI - G-quadruplex DNA and ligand interaction in living cells using NMR spectroscopy.
AB - Gathering structural information from biologically relevant molecules inside
living cells has always been a challenging task. In this work, we have used
multidimensional NMR spectroscopy to probe DNA G-quadruplexes inside living
Xenopus laevis oocytes. Some of these structures can be found in key regions of
chromosomes. G-quadruplexes are considered potential anticancer therapeutic
targets and several lines of evidence indirectly point out roles in key
biological processes, such as cell proliferation, genomic instability or
replication initiation. However, direct demonstrations of the existence of G
quadruplexes in vivo are scarce. Using SOFAST-HMQC type spectra, we probed a
tetramolecular G-quadruplex model made of d(TG4T)4 inside living Xenopus laevis
oocytes. Our observations lead us to conclude that the quadruplex structure is
formed within the cell and that the intracellular environment preferentially
selects a conformation that most resembles the one found in vitro under KCl
conditions. We also show for the first time that specific ligands targeting G
quadruplexes can be studied using high resolution NMR directly inside living
cells, opening new avenues to study ligand binding discrimination under
physiologically relevant conditions with atomic detail.
PMID- 28706696
TI - Oxide-supported Ir nanodendrites with high activity and durability for the oxygen
evolution reaction in acid PEM water electrolyzers.
AB - Reducing the noble-metal catalyst content of acid Polymer Electrolyte Membrane
(PEM) water electrolyzers without compromising catalytic activity and stability
is a goal of fundamental scientific interest and substantial technical importance
for cost-effective hydrogen-based energy storage. This study presents
nanostructured iridium nanodendrites (Ir-ND) supported on antimony doped tin
oxide (ATO) as efficient and stable water splitting catalysts for PEM
electrolyzers. The active Ir-ND structures exhibited superior structural and
morphological properties, such as particle size and surface area compared to
commercial state-of-art Ir catalysts. Supported on tailored corrosion-stable
conductive oxides, the Ir-ND catalysts exhibited a more than 2-fold larger
kinetic water splitting activity compared with supported Ir nanoparticles, and a
more than 8-fold larger catalytic activity than commercial Ir blacks. In single
cell PEM electrolyzer tests, the Ir-ND/ATO outperformed commercial Ir catalysts
more than 2-fold at technological current densities of 1.5 A cm-2 at a mere 1.80
V cell voltage, while showing excellent durability under constant current
conditions. We conclude that Ir-ND/ATO catalysts have the potential to
substantially reduce the required noble metal loading, while maintaining their
catalytic performance, both in idealized three-electrode set ups and in the real
electrolyzer device environments.
PMID- 28706697
TI - Nanopipettes: probes for local sample analysis.
AB - Nanopipettes (pipettes with diameters <1 MUm) were explored as pressure-driven
fluid manipulation tools for sampling nanoliter volumes of fluids. The
fundamental behavior of fluids confined in the narrow channels of the nanopipette
shank was studied to optimize sampling volume and probe geometry. This method was
utilized to collect nanoliter volumes (<10 nL) of sample from single Allium cepa
cells and live Drosophila melanogaster first instar larvae. Matrix assisted laser
desorption/ionization-mass spectrometry (MALDI-MS) was utilized to characterize
the collected sample. The use of nanopipettes for surface sampling of mouse brain
tissue sections was also explored. Lipid analyses were performed on mouse brain
tissues with spatial resolution of sampling as small as 50 MUm. Nanopipettes were
shown to be a versatile tool that will find further application in studies of
sample heterogeneity and population analysis for a wide range of samples.
PMID- 28706698
TI - A supramolecular strategy for tuning the energy level of naphthalenediimide:
Promoted formation of radical anions with extraordinary stability.
AB - We report a supramolecular strategy to promote and stabilize the formation of
naphthalenediimide (NDI) radical anions. The LUMO and HOMO energy of NDI are
lowered significantly by introducing cucurbit[7]uril (CB[7]) to each side of a
designed NDI molecule through supramolecular complexation. This promotes
efficiently the photo-induced electron transfer process between NDI and bromide
anions in aqueous solution. The resulting NDI supramolecular radical anions are
of outstanding stability. They are even stable in aqueous solution at higher
temperatures of 40 degrees C and 60 degrees C. It is anticipated that this
supramolecular strategy may provide a facile method for stabilizing radicals
towards the development of novel materials with spin-based properties and optical
properties in the visible and near-infrared regions.
PMID- 28706699
TI - Using the gravitational energy of water to generate power by separation of charge
at interfaces.
AB - When a fluid comes into contact with a solid surface, charge separates at the
interface. This study describes a method that harvests the gravitational energy
of water-available in abundance naturally, such as in rain and rivers-through the
separation of charge at the interface. Essentially, it is found that water can be
charged by flowing it across a solid surface under its own weight; thus, a
continuous flow of water can produce a constant supply of power. After optimizing
the system, a power of up to ~170 MUW (per Teflon tube of 2 mm in diameter) can
be generated. The efficiency, defined as the energy generated by the system over
the gravitational energy that the water losses, can reach up to ~3-4%. In order
to generate a continuous stream of positively-charged water, there should also be
a constant production of negatively-charged species in the system. Experimental
results suggest that the negative charge transfers constantly to the atmosphere
due to dielectric breakdown of air. With regards to applications related to high
electrical potential of water droplets, the amount of charge generated in a
single water droplet is found to be equivalent to that produced by charging the
water droplet with a high-voltage power supply operated at ~5 kV. In general, the
energy generated is clean, renewable, and technically simple and inexpensive to
produce.
PMID- 28706700
TI - In situ activation and monitoring of the evolution of the intracellular caspase
family.
AB - The evolution of the intracellular caspase family is crucial in cell apoptosis.
To evaluate this process, a universal platform of in situ activation and
monitoring of the evolution of intracellular caspase is designed. Using well
known gold nanostructure as a model of both nanocarrier and matter inducing the
cell apoptosis for photothermal therapy, a nanoprobe is prepared by assembly of
two kinds of dye-labelled peptides specific to upstream caspase-9 and downstream
caspase-3 as the signal switch, and folic acid as a targeting moiety. The energy
transfer from dyes to the gold nanocarrier at two surface plasmon resonance
absorption wavelengths leads to their fluorescence quenching. Upon endocytosis of
the nanoprobe to perform the therapy against cancer cells, the peptides are
successively cleaved by intracellular caspase activation with the evolution from
upstream to downstream, which lights up the fluorescence of the dyes
sequentially, and can be used to quantify both caspase-9 and caspase-3 activities
in cancer cells and to monitor their evolution in living mice. The recovered
fluorescence could also be used to assess therapeutic efficiency. This work
provides a novel powerful tool for studying the evolution of the intracellular
caspase family and elucidating the biological roles of caspases in cancer cell
apoptosis.
PMID- 28706701
TI - Nitrite reduction by copper through ligand-mediated proton and electron transfer.
AB - Nitrite reduction by a copper complex featuring a proton-responsive tripodal
ligand is demonstrated. Gaseous nitric oxide was confirmed as the sole NO X by
product in quantitative yield. DFT calculations predict that nitrite reduction
occurs via a proton and electron transfer process mediated by the ligand. The
reported mechanism parallels nitrite reduction by copper nitrite reductase.
PMID- 28706702
TI - A convergent total synthesis of ouabagenin.
AB - A convergent total synthesis of ouabagenin, an aglycon of cardenolide glycoside
ouabain, was achieved by assembly of the AB-ring, D-ring and butenolide moieties.
The multiply oxygenated cis-decalin structure of the AB-ring was constructed from
(R)-perillaldehyde through the Diels-Alder reaction and sequential oxidations.
The intermolecular acetal formation of the AB-ring and D-ring fragments, and
combination of the intramolecular radical and aldol reactions, assembled the
requisite steroidal skeleton in a stereoselective fashion. Finally,
stereoselective installation of the C17-butenolide via the Stille coupling and
hydrogenation led to ouabagenin.
PMID- 28706703
TI - Polymeric materials that convert local fleeting signals into global macroscopic
responses.
AB - We report a general design strategy for creating polymeric materials that are
capable of providing global, macroscopic changes in their properties in response
to specific local and fleeting stimuli. In a proof-of-concept demonstration, a
single polymer is used, yet it enables selective responses to specific stimuli,
and then internally drives a macroscopic change in the material (even in
locations not exposed to the stimulus), where the magnitude of change is
independent of the intensity of the applied stimulus.
PMID- 28706704
TI - Hydration of guanidinium depends on its local environment.
AB - Hydration of gaseous guanidinium (Gdm+) with up to 100 water molecules attached
was investigated using infrared photodissociation spectroscopy in the hydrogen
stretch region between 2900 and 3800 cm-1. Comparisons to IR spectra of low
energy computed structures indicate that at small cluster size, water interacts
strongly with Gdm+ with three inner shell water molecules each accepting two
hydrogen bonds from adjacent NH2 groups in Gdm+. Comparisons to results for
tetramethylammonium (TMA+) and Na+ enable structural information for larger
clusters to be obtained. The similarity in the bonded OH region for
Gdm(H2O)20+vs. Gdm(H2O)100+ and the similarity in the bonded OH regions between
Gdm+ and TMA+ but not Na+ for clusters with <50 water molecules indicate that
Gdm+ does not significantly affect the hydrogen-bonding network of water
molecules at large size. These results indicate that the hydration around Gdm+
changes for clusters with more than about eight water molecules to one in which
inner shell water molecules only accept a single H-bond from Gdm+. More effective
H-bonding drives this change in inner-shell water molecule binding to other water
molecules. These results show that hydration of Gdm+ depends on its local
environment, and that Gdm+ will interact with water even more strongly in an
environment where water is partially excluded, such as the surface of a protein.
This enhanced hydration in a limited solvation environment may provide new
insights into the effectiveness of Gdm+ as a protein denaturant.
PMID- 28706705
TI - An extended Tolerance Factor approach for organic-inorganic perovskites.
AB - Goldschmidt's concept of ionic Tolerance Factors was recently shown to be a
valuable guideline for the preparation of new compounds within the field of
organic-inorganic perovskites. Here, we extend this approach and calculate
Tolerance Factors for over 2500 amine-metal-anion permutations of the periodic
table. The results suggest the potential existence of more than 600 undiscovered
hybrid perovskites including alkaline earth metal and lanthanide based materials.
PMID- 28706706
TI - Generation of 1,2-azaboretidines via reduction of ADC borane adducts.
AB - Reaction of the acyclic (diamino)carbene (ADC) :C(NiPr2)2 (1) with different
dihaloboranes of the type RBX2 (R = Mes, Dur; X = Cl, Br) smoothly afforded a
novel class of ADC-stabilized borane adducts. For MesBBr2 however, the reaction
did not stop at the adduct level, but an uncommon rearrangement process occurred,
which eventually resulted in the formation of a 5-membered boracycle after
elimination of mesitylene. Chemical reduction of the ADC borane adducts by KC8
selectively yielded air stable 1,2-azaboretidines. Detailed DFT studies suggest a
reduction mechanism involving a highly reactive borylene intermediate, which is
converted into the boracycles via a rearrangement/C-H activation sequence.
PMID- 28706707
TI - Stable porphyrin Zr and Hf metal-organic frameworks featuring 2.5 nm cages: high
surface areas, SCSC transformations and catalyses.
AB - Two isostructural porphyrin Zr and Hf metal-organic frameworks (FJI-H6 and FJI
H7) are rationally synthesized, and are constructed from 2.5 nm cubic cages.
Notably, they both possess high water and chemical stability and can undergo
single-crystal to single-crystal transformations to embed Cu2+ ions into the open
porphyrin rings. FJI-H6 has a high BET surface area of 5033 m2 g-1. Additionally,
they exhibit promising catalytic abilities to convert CO2 and epoxides into
cyclic carbonates at ambient conditions.
PMID- 28706708
TI - Bottom-up on-crystal in-chip formation of a conducting salt and a view of its
restructuring: from organic insulator to conducting "switch" through microfluidic
manipulation.
AB - The chemical modification of an immobilized single crystal in a fluid cell is
reported, whereby a material with switching functions is generated in situ by
generating a chemical reagent in the flow. Crystals of the insulating organic
crystal of TCNQ (tetracyanoquinodimethane) were grown in a microfluidic channel
and were trapped using a pneumatic valve, a nascent technique for materials
manipulation. They were subsequently reduced using solution-deposited silver to
provide a conducting material in situ by a heterogeneous reaction. Removal of the
new material from the chip proved it to be the silver salt of reduced TCNQ.
Uniquely, conducting atomic force microscope (CAFM) studies show three regions in
the solid. The localized original neutral organic material crystal is shown to be
an insulator but to produce areas with Ohmic conducting characteristics after
reduction. This inhomogeneous doping provides an opportunity for probing
electrical materials properties side by side. Measurements with the CAFM witness
this conducting material where the TCNQ is fully transformed to the silver salt.
Additionally, an intermediate phase is observed that exhibits bipolar resistive
switching typical of programmable resistive memories. Raman microscopy proves the
conversion of the material in specific regions and clearly defines the
intermediate phase region that could be responsible for the switching effect in
related materials. This kind of "on crystal chemistry" exploiting immobilization
and masking by a pneumatic clamp in a microfluidic channel shows how material can
be selectively converted to give different functionalities in the same material
piece, even though it is not a single crystal to single crystal conversion, and
beckons exploitation for the preparation of systems relevant for molecular
electronics as well as other areas where chemical manipulation of single crystals
could be beneficial.
PMID- 28706709
TI - What causes extended layering of ionic liquids on the mica surface?
AB - Extended layering of ionic liquids (ILs) on the mica surface has been reported by
several groups previously and it is generally accepted that the electrostatic
interaction at the IL/mica interface is critical to the observed extended
layering. Here we report that, indeed, water adsorption on the mica surface is
the key to the extended layering of ionic liquids. The atomic force microscopy
(AFM), attenuated total reflectance-fourier transform infrared spectroscopy (ATR
FTIR) and contact angle (CA) results show that ionic liquids form extended
layering on a mica surface under ambient conditions when water is adsorbed on the
mica surface under such conditions. However, when airborne hydrocarbon
contaminants replace the water on the mica surface at the elevated temperatures,
instead of layering, ionic liquids exhibit droplet structure, i.e., dewetting.
Based on the experimental results, we propose that water enables ion exchange
between K+ and the cations of ILs on the mica surface and thus triggers the
ordered packing of cations/anions in ILs, resulting in extended layering.
PMID- 28706710
TI - The role of capsule stiffness on cellular processing.
AB - Particle stiffness is emerging as an important parameter in determining the cell
uptake dynamics of particles. Understanding the effects of capsule stiffness on
their biological behavior is essential for the development of polymer capsules as
therapeutic carriers. Herein, we report the preparation of polysaccharide
capsules via atom transfer radical polymerization-mediated continuous assembly of
polymers (CAPATRP) on silica templates using methacrylated hyaluronic acid (HA)
as the macrocrosslinker. This approach affords HA capsules with controllable wall
thickness and tunable stiffness. The influence of capsule stiffness on cellular
interaction and intracellular distribution is systematically investigated using
flow cytometry, imaging flow cytometry, and deconvolution microscopy. The softest
HA capsules with a stiffness (gamma) of 7.5 mN m-1 possess higher cell surface
binding and cellular association when compared to stiffer capsules with gamma of
17.6-28.9 mN m-1. Furthermore, the uptake of HA capsules is a stiffness-dependent
process, with slower and less cellular internalization observed with increasing
capsule stiffness. Nevertheless, regardless of the stiffness, all internalized
capsules are deformed and located in the lysosomes. These findings offer insights
into the influence of capsule stiffness on cellular interaction as well as
intracellular fate, providing information for the design of rational polymer
capsules for biomedical applications.
PMID- 28706711
TI - Mutual stabilisation between MII4L6 tetrahedra and MIIX42- metallate guests.
AB - A complex host-guest equilibrium employing metal ions incorporated into both the
host and guest is discussed. MIIX42- metallate guests are shown to provide a good
size and shape match for encapsulation within the M4L6 tetrahedral capsules,
facilitating the generation of previously unreported Zn4L6 complexes.
Displacement of the initial, primary template anion (ZnBr42-) by a secondary
template anion (ClO4-) is shown to result in the formation of a pentagonal
prismatic Zn10L15 structure that incorporates both Br- and ClO4-. Furthermore,
the formation of heterometallic complexes provides direct evidence for metal
exchange between the guest and host complex.
PMID- 28706712
TI - Self-assembly of "patchy" nanoparticles: a versatile approach to functional
hierarchical materials.
AB - The solution-phase self-assembly or "polymerization" of discrete colloidal
building blocks, such as "patchy" nanoparticles and multicompartment micelles, is
attracting growing attention with respect to the creation of complex hierarchical
materials. This approach represents a versatile method with which to transfer
functionality at the molecular level to the nano- and microscale, and is often
accompanied by the emergence of new material properties. In this perspective we
highlight selected recent examples of the self-assembly of anisotropic
nanoparticles which exploit directional interactions introduced through their
shape or surface chemistry to afford a variety of hierarchical materials. We
focus in particular on the solution self-assembly of block copolymers as a means
to prepare multicompartment or "patchy" micelles. Due to their potential for
synthetic modification, these constructs represent highly tuneable building
blocks for the fabrication of a wide variety of functional assemblies.
PMID- 28706713
TI - Chemical principles underpinning the performance of the metal-organic framework
HKUST-1.
AB - A common feature of multi-functional metal-organic frameworks is a metal dimer in
the form of a paddlewheel, as found in the structure of Cu3(btc)2 (HKUST-1). The
HKUST-1 framework demonstrates exceptional gas storage, sensing and separation,
catalytic activity and, in recent studies, unprecedented ionic and electrical
conductivity. These results are a promising step towards the real-world
application of metal-organic materials. In this perspective, we discuss progress
in the understanding of the electronic, magnetic and physical properties of HKUST
1, representative of the larger family of Cu...Cu containing metal-organic
frameworks. We highlight the chemical interactions that give rise to its
favourable properties, and which make this material well suited to a range of
technological applications. From this analysis, we postulate key design
principles for tailoring novel high-performance hybrid frameworks.
PMID- 28706714
TI - Porous ionic liquids: synthesis and application.
AB - Solidification of fluidic ionic liquids into porous materials yields porous ionic
networks that combine the unique characteristics of ionic liquids with the common
features of polymers and porous materials. This minireview reports the most
recent advances in the design of porous ionic liquids. A summary of the synthesis
of ordered and disordered porous ionic liquid-based nanoparticles or membranes
with or without templates is provided, together with the new concept of room
temperature porous ionic liquids. As a versatile platform for functional
materials, porous ionic liquids have shown widespread applications in catalysis,
adsorption, sensing, actuation, etc. This new research direction towards ionic
liquids chemistry is still in its early stages but has great potential.
PMID- 28706715
TI - A general approach to the design of allosteric, transcription factor-regulated
DNAzymes.
AB - Here we explore a general strategy for the rational design of nucleic acid
catalysts that can be allosterically activated by specific nucleic-acid binding
proteins. To demonstrate this we have combined a catalytic DNAzyme sequence and
the consensus sequence recognized by specific transcription factors to create a
construct exhibiting two low-energy conformations: a more stable conformation
lacking catalytic activity and lacking the transcription factor binding site, and
a less stable conformation that is both catalytically active and competent to
bind the transcription factor. The presence of the target transcription factor
pushes the equilibrium between these states towards the latter conformation,
concomitantly activating catalysis. To demonstrate this we have designed and
characterized two peroxidase-like DNAzymes whose activities are triggered upon
binding either TATA binding protein or the microphthalmia-associated
transcription factor. Our approach augments the current tool kit for the
allosteric control of DNAzymes and ribozymes and, because transcription factors
control many key biological functions, could have important clinical and
diagnostic applications.
PMID- 28706716
TI - Exceptional CO2 working capacity in a heterodiamine-grafted metal-organic
framework.
AB - An amine-functionalized metal-organic framework (MOF), dmen-Mg2(dobpdc) (dmen =
N,N-dimethylethylenediamine), which contains a heterodiamine with both primary
and tertiary amines, was prepared via a post-synthetic method. This material
exhibits a significant selectivity factor for CO2 over N2 that is commensurate
with top-performing MOFs. It is remarkable that the solid is fully regenerated
under vacuum or flowing Ar at low desorption temperatures, and following this can
take up CO2 at more than 13 wt%. An exceptionally high working capacity is
achieved at low regeneration temperatures and after exposure to humid conditions,
which are important parameters for a real post-combustion CO2 capture process.
PMID- 28706717
TI - Carbene catalyzed umpolung of alpha,beta-enals: a reactivity study of diamino
dienols vs. azolium enolates, and the characterization of advanced reaction
intermediates.
AB - Since their discovery by Bode and Glorius in 2004, N-heterocyclic carbene
catalyzed conjugate umpolung reactions of alpha,beta-enals have been postulated
to involve the formation of diamino dienols ("homoenolates") and/or azolium
enolates ("enolates"), typically followed by addition to electrophiles, e.g.
Michael-acceptors. In this article, we provide evidence, for the first time, for
the postulated individual and specific reactivity patterns of diamino dienols
(gamma-C-C-bond formation) vs. azolium enolates (beta-C-C-bond formation). Our
study is based on the pre-formation of well defined diamino dienols and azolium
enolates, and the in situ NMR monitoring of their reactivities towards enone
electrophiles. Additionally, reaction intermediates were isolated and
characterized, inter alia by X-ray crystallography.
PMID- 28706718
TI - Functional modulation and directed assembly of an enzyme through designed non
natural post-translation modification.
AB - Post-translational modification (PTM) modulates and supplements protein
functionality. In nature this high precision event requires specific motifs
and/or associated modification machinery. To overcome the inherent complexity
that hinders PTM's wider use, we have utilized a non-native biocompatible Click
chemistry approach to site-specifically modify TEM beta-lactamase that adds new
functionality. In silico modelling was used to design TEM beta-lactamase variants
with the non-natural amino acid p-azido-l-phenylalanine (azF) placed at
functionally strategic positions permitting residue-specific modification with
alkyne adducts by exploiting strain-promoted azide-alkyne cycloaddition. Three
designs were implemented so that the modification would: (i) inhibit TEM activity
(Y105azF); (ii) restore activity compromised by the initial mutation (P174azF);
(iii) facilitate assembly on pristine graphene (W165azF). A dibenzylcyclooctyne
(DBCO) with amine functionality was enough to modulate enzymatic activity.
Modification of TEMW165azF with a DBCO-pyrene adduct had little effect on
activity despite the modification site being close to a key catalytic residue but
allowed directed assembly of the enzyme on graphene, potentially facilitating the
construction of protein-gated carbon transistor systems.
PMID- 28706719
TI - Absolute structure determination of compounds with axial and planar chirality
using the crystalline sponge method.
AB - The absolute stereochemistry of compounds with axial and planar chirality is
successfully determined by the crystalline sponge method without crystallization
or derivatization of the compounds. This method is applied to absolute structure
determination in the asymmetric synthesis of unique compounds with axial and
planar chirality.
PMID- 28690832
TI - Validation of commercial ERK antibodies against the ERK orthologue of the
scleractinian coral Stylophora pistillata.
AB - The extracellular signal-regulated protein kinase (ERK) signalling pathway
controls key cellular processes, such as cell cycle regulation, cell fate
determination and the response to external stressors. Although ERK functions are
well studied in a variety of living organisms ranging from yeast to mammals, its
functions in corals are still poorly known. The present work aims to give
practical tools to study the expression level of ERK protein and the activity of
the ERK signalling pathway in corals. The antibody characterisation experiment
was performed five times and identical results were obtained. The present study
validated the immune-reactivity of commercially available antibodies directed
against ERK and its phosphorylated/activated forms on protein extracts of the
reef-building coral Stylophora pistillata.
PMID- 28706720
TI - Endotype-driven treatment in chronic upper airway diseases.
AB - Rhinitis and rhinosinusitis are the two major clinical entities of chronic upper
airway disease. Chronic rhinosinusitis (CRS) and allergic rhinitis (AR) affect
respectively up to 10 and 30% of the total population, hence being associated
with an important socio-economic burden. Different phenotypes of rhinitis and CRS
have been described based on symptom severity and duration, atopy status, level
of control, comorbidities and presence or absence of nasal polyps in CRS. The
underlying pathophysiological mechanisms are diverse, with different, and
sometimes overlapping, endotypes being recognized. Type 2 inflammation is well
characterized in both AR and CRS with nasal polyps (CRSwNP), whereas type 1
inflammation is found in infectious rhinitis and CRS without nasal polyps
(CRSsNP). The neurogenic endotype has been demonstrated in some forms of non
allergic rhinitis. Epithelial barrier dysfunction is shown in AR and CRSwNP.
Emerging therapies are targeting one specific pathophysiological pathway or
endotype. This endotype-driven treatment approach requires careful selection of
the patient population who might benefit from a specific treatment. Personalized
medicine is addressing the issue of providing targeted treatment for the right
patient and should be seen as one aspect of the promising trend towards precision
medicine. This review provides a comprehensive overview of the current state of
endotypes, biomarkers and targeted treatments in chronic inflammatory conditions
of the nose and paranasal sinuses.
PMID- 28706722
TI - 'Phoenicibacter massiliensis' gen. nov., sp. nov., a new bacterium isolated from
the human gut of a pygmy woman.
AB - This study supports the main characteristics of the new genus and new species
'Phoenicibacter massiliensis' strain Marseille-P3241T (CSUR P3241), a new
bacterium isolated from a stool sample of a healthy 47-year-old pygmy woman.
PMID- 28706723
TI - Noncontiguous finished genome sequences and description of Bacillus
massiliglaciei, Bacillus mediterraneensis, Bacillus massilinigeriensis, Bacillus
phocaeensis and Bacillus tuaregi, five new species identified by culturomics.
AB - Microbial culturomics, which investigates microbial diversity by combining
diversified culture conditions, matrix-assisted laser desorption/ionization time
of-flight mass spectrometry and 16S rDNA identification, allowed to identify five
new species within the Bacillus genus. Bacillus massiliglaciei strain Marseille
P2600T, Bacillus mediterraneensis strain Marseille-P2384T, Bacillus
massilinigeriensis strain Marseille-P2366T, Bacillus tuaregi strain Marseille
P2489T and Bacillus phocaeensis strain SIT16T are each the type strain of the
corresponding bacterial species. These strains, the genomes of which are
described here, are facultative anaerobic Gram-positive bacilli. Here, we
describe the main characteristics of each bacterium and present their complete
genome sequence and annotation.
PMID- 28706724
TI - Editorial: 'The healthcare systems have a growing need for systems that enable
holistic approaches for treatment of age-related conditions, supporting active
and healthy ageing and interactions with the patients, their caregivers and
healthcare professionals.'
PMID- 28706725
TI - Avatars and virtual agents - relationship interfaces for the elderly.
AB - In the Digital Era, the authors witness a change in the relationship between the
patient and the care-giver or Health Maintenance Organization's providing the
health services. Another fact is the use of various technologies to increase the
effectiveness and quality of health services across all primary and secondary
users. These technologies range from telemedicine systems, decision making tools,
online and self-services applications and virtual agents; all providing
information and assistance. The common thread between all these digital
implementations, is they all require human machine interfaces. These interfaces
must be interactive, user friendly and inviting, to create user involvement and
cooperation incentives. The challenge is to design interfaces which will best fit
the target users and enable smooth interaction especially, for the elderly users.
Avatars and Virtual Agents are one of the interfaces used for both home care
monitoring and companionship. They are also inherently multimodal in nature and
allow an intimate relation between the elderly users and the Avatar. This study
discusses the need and nature of these relationship models, the challenges of
designing for the elderly. The study proposes key features for the design and
evaluation in the area of assistive applications using Avatar and Virtual agents
for the elderly users.
PMID- 28706726
TI - Community-based trials of mobile solutions for the detection and management of
cognitive decline.
AB - This study focused on the development and usability evaluation of EnCare
diagnostics (ECD) and the brain fit plan (BFP) in healthy older adults,
cognitively impaired and physically impaired individuals. ECD is proposed as a
novel solution to cognitive assessment based on colour selection. BFP is a novel
solution to personalised cognitive stimulation. The study consisted of two trials
designed to evaluate the usability of the apps. Trial 1 involved 11 healthy older
adults and four older adults with physical impairments who undertook ECD and mini
mental state examination (MMSE) once per month for 4 months with only those with
physical impairments also completing the BFP daily. Trial 2 involved eight older
adults diagnosed with early stage dementia who completed MMSE and ECD once per
month for 6 months. In Trial 1, 10 out of 11 participants enjoyed the trial and
managed the usability of the app easily. A 75% drop out was observed in response
to the BFP with issues of dexterity and lack of understanding on how to use the
technology being the main reasons for lack of compliance. Four out of eight
participants completed Trial 2 with most of the participants having no usability
issues. This usability study demonstrated that ECD is highly acceptable in both
healthy older adults and those with early stage dementia when given the shorter
versions to accommodate their diagnosis. The BFP was not suited to this
population of participants.
PMID- 28706727
TI - PD_Manager: an mHealth platform for Parkinson's disease patient management.
AB - PD_Manager is a mobile health platform designed to cover most of the aspects
regarding the management of Parkinson's disease (PD) in a holistic approach.
Patients are unobtrusively monitored using commercial wrist and insole sensors
paired with a smartphone, to automatically estimate the severity of most of the
PD motor symptoms. Besides motor symptoms monitoring, the patient's mobile
application also provides various non-motor self-evaluation tests for assessing
cognition, mood and nutrition to motivate them in becoming more active in
managing their disease. All data from the mobile application and the sensors is
transferred to a cloud infrastructure to allow easy access for clinicians and
further processing. Clinicians can access this information using a separate
mobile application that is specifically designed for their respective needs to
provide faster and more accurate assessment of PD symptoms that facilitate
patient evaluation. Machine learning techniques are used to estimate symptoms and
disease progression trends to further enhance the provided information. The
platform is also complemented with a decision support system (DSS) that notifies
clinicians for the detection of new symptoms or the worsening of existing ones.
As patient's symptoms are progressing, the DSS can also provide specific
suggestions regarding appropriate medication changes.
PMID- 28706728
TI - Effects of ageing and Alzheimer disease on haemodynamic response function: a
challenge for event-related fMRI.
AB - Functional magnetic resonance imaging (fMRI) can generate brain images that show
neuronal activity due to sensory, cognitive or motor tasks. Haemodynamic response
function (HRF) may be considered as a biomarker to discriminate the Alzheimer
disease (AD) from healthy ageing. As blood-oxygenation-level-dependent fMRI
signal is much weak and noisy, particularly for the elderly subjects, a robust
method is necessary for HRF estimation to efficiently differentiate the AD. After
applying minimum description length wavelet as an extra denoising step,
deconvolution algorithm is here employed for HRF estimation, substituting the
averaging method used in the previous works. The HRF amplitude peaks are compared
for three groups HRF of young, non-demented and demented elderly groups for both
vision and motor regions. Prior works often reported significant differences in
the HRF peak amplitude between the young and the elderly. The authors'
experimentations show that the HRF peaks are not significantly different
comparing the young adults with the elderly (either demented or non-demented). It
is here demonstrated that the contradictory findings of the previous studies on
the HRF peaks for the elderly compared with the young are originated from the
noise contribution in fMRI data.
PMID- 28706729
TI - A retrospective review of the Pediatric Development Clinic implementation: a
model to improve medical, nutritional and developmental outcomes of at-risk under
five children in rural Rwanda.
AB - BACKGROUND: As more high-risk newborns survive the neonatal period, they remain
at significant medical, nutritional, and developmental risk. However, no follow
up system for early intervention exists in most developing countries. In 2014, a
novel Pediatric Development Clinic (PDC) was implemented to provide comprehensive
follow-up to at-risk under-five children, led by nurses and social workers in a
district hospital and surrounding health centers in rural Rwanda. METHODS: At
each PDC visit, children undergo clinical/nutritional assessment and caregivers
participate in counseling sessions. Social assessments identify families needing
additional social support. Developmental assessment is completed using Ages and
Stages Questionnaires. A retrospective medical record review was conducted to
evaluate the first 24 months of PDC implementation for patients enrolled between
April 2014-December 2015 in rural Rwanda. Demographic and clinical
characteristics of patients and their caregivers were described using frequencies
and proportions. Completion of different core components of PDC visits were
compared overtime using Fisher's Exact test and p-values calculated using trend
analysis. RESULTS: 426 patients enrolled at 5 PDC sites. 54% were female, 44%
were neonates and 35% were under 6 months at enrollment. Most frequent referral
reasons were prematurity/low birth weight (63%) and hypoxic-ischemic
encephalopathy (34%). In 24 months, 2787 PDC visits were conducted. Nurses
consistently completed anthropometric measurements (age, weight, height) at all
visits. Some visit components were inconsistently recorded, including adjusted
age (p = 0.003), interval growth, danger sign assessment, and feeding
difficulties (p < 0.001). Completion of other visit components, such as child
development counseling and play/stimulation activities, were low but improved
with time (p < 0.001). CONCLUSIONS: It is feasible to implement PDCs with non
specialized providers in rural settings as we were able to enroll a diverse group
of high-risk infants. We are seeing an improvement in services offered at PDCs
over time and continuous quality improvement efforts are underway to strengthen
current gaps. Future studies looking at the outcomes of the children benefiting
from the PDC program are underway.
PMID- 28706730
TI - Body mass index associations between mother and offspring from birth to age 18:
the Fels Longitudinal Study.
AB - BACKGROUND: Parental obesity is a known determinant of childhood obesity.
Previous research has shown a strong maternal influence on body mass index (BMI)
during infancy and early childhood. OBJECTIVES: The purpose of this research was
to investigate the BMI associations between mother and offspring from birth to
age 18 years. METHODS: Participants were selected from the Fels Longitudinal
Study. The current study sample includes 427 (215 mother/son and 212
mother/daughter) mother/child pairs. These pairs are repeatedly measured at
multiple age groups in children, resulting in a total of 6,263 (3,215 mother/son,
3,048 mother/daughter) observations for data analysis. Inclusion criteria were
children with measured height and weight for BMI collected at ages 0 to 18 years
and their mother with BMI data. Maternal influences of BMI on offspring BMI from
birth to early adulthood were analyzed by Spearman correlations and linear
regression analyses. RESULTS: Mother/son BMI correlations became statistically
significant (p <= 0.05) at age 5-6 years and were significant through puberty and
into early adulthood at age 18 years. Mother/daughter correlations became
significant at age 1.5 years and also continued through adolescence, puberty and
early adulthood at age 18 years. Associations persisted after the study sample
was grouped into life stages and adjusted for decade of birth and parity.
CONCLUSIONS: The mother/daughter relationship was more strongly correlated than
the mother/son relationship and also became statistically significant at an
earlier age than boys.
PMID- 28706731
TI - Household wealth status and overweight and obesity among adult women in
Bangladesh and Nepal.
AB - BACKGROUND: In South Asia, women were reported to be more likely to have higher
normal body weight. However, nationally representative evidence on the
association between socioeconomic status and body weight in terms of regional cut
offs for body mass index is limited for South Asian women. This study aimed to
address this gap by investigating the association between household wealth status
and overweight and obesity among adult women in Bangladesh and Nepal.
METHODOLOGY: Cross-sectional data on 6,144 Nepalese and 17,683 Bangladeshi women
were obtained from most recent Demographic and Health Surveys in these countries.
Cut-offs for overweight and obesity were defined as per World Health Organization
recommendation for South Asian population. RESULTS: The mean age of respondents
was respectively 28.76 (9.74) and 31.01 (9.21) in Nepal and Bangladesh. The
prevalence of obesity and overweight was respectively 13.5% and 14% for Nepal and
15.3% and 24.2% for Bangladesh. Compared with women living in poorest households,
the odds of being overweight were respectively 3.44, 2.12, 1.46 and 1.19 times
higher for women living in richest, richer, middle and poorer wealth status
households in Nepal. In Bangladesh, compared with poorest households, women in
richest, richer, middle and poorer households had respectively 98%, 60%, 32% and
22% higher odds of being overweight. Among Bangladeshi women, the odds of being
obese in richest households were 4.62 (adjusted odds ratio = 4.572; 95%
confidence interval = 3.813-5.484) times and among Nepalese women 8.54 (adjusted
odds ratio = 8.452; 95% confidence interval = 5.228-13.663) times higher compared
with those in poorest households. CONCLUSION: Higher household wealth is
associated with an increased likelihood of being overweight and obese among adult
women in Bangladesh and Nepal. Using the regional cut-offs for body mass index
shows that the prevalence of obesity among women has for the first time exceeded
that of overweight in both countries.
PMID- 28706732
TI - Age increases MCP-1 level in association with bariatric surgery operating time
and metabolic risk severity.
AB - OBJECTIVE: Assess the role of inflammation on operating time in younger vs. older
bariatric surgery patients. METHODS: Fifty-five younger (F: 46, Age: 34.9 +/- 4.0
years, body mass index [BMI]: 48.2 +/- 1.0 kg m-2) and 48 older (F: 34, Age: 57.0
+/- 5.1 years, BMI: 46.8 +/- 1.0 kg m-2) adults were studied prior to surgery.
Blood pressure, glycaemic control (fasting glucose/insulin, HbA1c), lipids (high
density lipoprotein and triglycerides) and inflammation (monocyte chemoattractant
protein-1 [MCP-1]) were assessed. Metabolic risk severity z-scores were
calculated from clinical outcomes. Omental adipose biopsies were collected at
surgery for MCP-1 protein analysis. Operating time was used to characterize
surgical difficulty. RESULTS: Older vs. younger adults had higher HbA1c (P =
0.03). There was no difference in BMI, lipids, metabolic risk severity or insulin
between groups, but operating time was longer in older vs. younger individuals (P
= 0.04). Circulating MCP-1 was also elevated in older vs. younger adults (P =
0.04) independent of HbA1c, although this was not explained by omental fat.
Nevertheless, serum MCP-1 was associated with increased metabolic risk severity
(R = 0.27, P = 0.01). In addition, operating time was linked to HbA1c (R = 0.30,
P = 0.01) and omental MCP-1 protein (R = 0.31, P < 0.01). CONCLUSIONS: MCP-1 is
associated with longer operating time and increased metabolic risk severity in
older bariatric patients independent of glycaemic control. Pre-operative
treatment of inflammation may be required to enhance surgery effectiveness.
PMID- 28706733
TI - The effect of characteristics of proteins fed during gestation and lactation on
development of metabolic syndrome in dams and male offspring of Wistar rats.
AB - OBJECTIVE: The objective of the study is to examine the role of characteristics
of proteins in maternal and weaning diets on risk of metabolic syndrome in male
offspring. METHODS: Pregnant Wistar rats were allocated to two groups (n = 12)
and were fed the AIN-93G diets based on either intact protein-based diet (IPD) or
mixed amino acid-based diet (AAD) from day 3 of gestation throughout gestation
and lactation. Male offspring were weaned to either an IPD or AAD diet for 18
weeks. RESULTS: In dams, AAD group had lower body weight in post-partum period
and higher pulse rate compared with IPD group. In pups born to AAD dams, birth
weight and body weight were significantly lower, and systolic blood pressure and
fasting blood glucose were significantly higher compared with those born to IPD
dams. Fat/weight ratio, insulin and homeostasis model assessment of insulin
resistance were not influenced by either maternal or weaning diet. CONCLUSIONS:
These results indicate that the physico-chemical structure of proteins fed to
dams is important in altering risk factors of metabolic syndrome in the
offspring, while weaning diets do not seem to play a role. IPD had more
favourable effect than AAD. These results may also indicate that dietary
recommendations during development must be updated based on physiological
properties of dietary proteins that are beyond their nutritional role.
PMID- 28706734
TI - BRCA1 and BRCA2 mutations and treatment strategies for breast cancer.
AB - Breast cancer is a global burden with a woman's lifetime risk of developing
breast cancer at 1 in 8. Although breast cancer is a disease that affects mostly
women, the lifetime risk in men is about 1 in 1000. Most cases of breast cancer
are associated with somatic mutations in breast cells that are acquired during a
person's lifetime. In this scenario, the mutations are not inherited and they do
not cluster in families. In hereditary breast cancer, the specific genetic
factors involved will determine the inherited cancer risk. Inherited mutations in
the BRCA1 or BRCA2 genes have been well-described, but mutations in ATM, CDH1,
CHEK2, PALB2, PTEN, STK11, and TP53 also confer breast cancer risk. Understanding
the functional significance of hereditary mutations has opened new paths for
breast cancer prevention and is uncovering promising treatment strategies.
PMID- 28706735
TI - The importance of copy number variation in congenital heart disease.
AB - Congenital heart disease (CHD) is the most common class of major malformations in
humans. The historical association with large chromosomal abnormalities
foreshadowed the role of submicroscopic rare copy number variations (CNVs) as
important genetic causes of CHD. Recent studies have provided robust evidence for
these structural variants as genome-wide contributors to all forms of CHD,
including CHD that appears isolated without extra-cardiac features. Overall, a
CNV-related molecular diagnosis can be made in up to one in eight patients with
CHD. These include de novo and inherited variants at established (chromosome
22q11.2), emerging (chromosome 1q21.1), and novel loci across the genome.
Variable expression of rare CNVs provides support for the notion of a genetic
spectrum of CHD that crosses traditional anatomic classification boundaries.
Clinical genetic testing using genome-wide technologies (e.g., chromosomal
microarray analysis) is increasingly employed in prenatal, paediatric and adult
settings. CNV discoveries in CHD have translated to changes to clinical
management, prognostication and genetic counselling. The convergence of findings
at individual gene and at pathway levels is shedding light on the mechanisms that
govern human cardiac morphogenesis. These clinical and research advances are
helping to inform whole-genome sequencing, the next logical step in delineating
the genetic architecture of CHD.
PMID- 28706736
TI - Peri-exposure protection against Nipah virus disease using a single-dose
recombinant vesicular stomatitis virus-based vaccine.
AB - Nipah virus is a zoonotic paramyxovirus that causes severe disease in humans and
animals. Due to almost yearly outbreaks in Bangladesh, and a large outbreak in
Malaysia that lead to the shutdown of swine export, Nipah virus is both a threat
to public health and the economy. Infection is associated with respiratory
distress, encephalitis and human-to-human transmission, resulting in high case
fatality rates during outbreaks. This study aims to address the amount of time
needed until protection from a recombinant vesicular stomatitis virus-based
vaccine candidate expressing the Nipah virus glycoprotein (G), which we have
previously shown to protect hamsters and non-human primates when administered 28
days before challenge. We found that a single-dose vaccination, when administered
1 day before challenge, reduced viral load, limited pathology and fully protected
hamsters from Nipah virus infection. The vaccine was even partially protective
when administered at early time points following challenge with Nipah virus.
These data indicate that a single administration of this vaccine to high-risk
individuals, such as family members and health-care workers of infected patients,
could be protective and useful for reducing human-to-human transmission and
curbing an outbreak.
PMID- 28706737
TI - The Prevalence of Visual Acuity Impairment among School Children at Arada Subcity
Primary Schools in Addis Ababa, Ethiopia.
AB - BACKGROUND: Visual impairment and blindness are major public health problems in
developing countries where there is no enough health-care service. OBJECTIVE: To
determine the prevalence of visual impairment among school children. MATERIALS
AND METHODS: A school-based cross-sectional study was conducted between 15 June
2015 and 30 November 2015 at Arada subcity primary schools, Addis Ababa,
Ethiopia. Two schools were selected randomly, and 378 students were screened from
grades 1 to 8 using systematic random sampling method. Snellen chart was used for
visual acuity test. Students who had visual acuity of <=6/12 were further
examined by an ophthalmologist to diagnose the reason for low vision. Data was
analyzed using SPSS version 20. RESULTS: A total of 378 students were screened,
and 192 (50.8%) were females and the remaining 186 (49.2%) were males. The
prevalence of visual impairment (VA) of <=6/12 on either eye was 5.8%, VA < 6/18
on either eye was 1.1%, and VA < 6/18 on the better eye was 0.53%. In this study,
color blindness [OR: 19.65, 95% CI (6.01-64.33)] was significantly associated
with visual acuity impairment. CONCLUSION: The prevalence of visual impairment
among school children in the study area was 5.8% and school screening is
recommended.
PMID- 28706738
TI - Influence on Adiposity and Atherogenic Lipaemia of Fatty Meals and Snacks in
Daily Life.
AB - The present work reviewed the connections of changes in consumption of high-fat
food with changes in adiposity and lipaemia in adults with overweight or obesity.
Hyperlipaemia from higher fat meals and excessive adiposity contributes to
atherogenic process. Low-fat diet interventions decrease body fat, lipaemia, and
atherosclerosis markers. Inaccuracy of physical estimates of dietary fat intake
remains, however, a limit to establishing causal connections. To fill this gap,
tracking fat-rich eating episodes at short intervals quantifies the behavioural
frequency suggested to measure (by regression of changes in real time) direct
effects of this eating pattern on adiposity and atherogenic lipaemia. Such
evidence will provide the basis for an approach focused on a sustained decrease
in frequency of fatty meals or snacks to reduce obesity, hyperlipaemia, and
atherosclerosis.
PMID- 28706739
TI - Emulation with Organic Memristive Devices of Impairment of LTP Mechanism in
Neurodegenerative Disease Pathology.
AB - We explore and demonstrate the extension of the synapse-mimicking properties of
memristive devices to a dysfunctional synapse as it occurs in the Alzheimer's
disease (AD) pathology. The ability of memristive devices to reproduce synapse
properties such as LTP, LTD, and STDP has been already widely demonstrated, and
moreover, they were used for developing artificial neuron networks (perceptrons)
able to simulate the information transmission in a cell network. However, a major
progress would be to extend the common sense of neuromorphic device even to the
case of dysfunction of natural synapses. Can memristors efficiently simulate
them? We provide here evidences of the ability of emulating the dysfunctional
synaptic behavior typical of the AD pathology with organic memristive devices
considering the effect of the disease not only on a single synapse but also in
the case of a neural network, composed by numerous synapses.
PMID- 28706740
TI - Action Video Game Experience Related to Altered Large-Scale White Matter
Networks.
AB - With action video games (AVGs) becoming increasingly popular worldwide, the
cognitive benefits of AVG experience have attracted continuous research attention
over the past two decades. Research has repeatedly shown that AVG experience can
causally enhance cognitive ability and is related to neural plasticity in gray
matter and functional networks in the brain. However, the relation between AVG
experience and the plasticity of white matter (WM) network still remains unclear.
WM network modulates the distribution of action potentials, coordinating the
communication between brain regions and acting as the framework of neural
networks. And various types of cognitive deficits are usually accompanied by
impairments of WM networks. Thus, understanding this relation is essential in
assessing the influence of AVG experience on neural plasticity and using AVG
experience as an interventional tool for impairments of WM networks. Using graph
theory, this study analyzed WM networks in AVG experts and amateurs. Results
showed that AVG experience is related to altered WM networks in prefrontal
networks, limbic system, and sensorimotor networks, which are related to
cognitive control and sensorimotor functions. These results shed new light on the
influence of AVG experience on the plasticity of WM networks and suggested the
clinical applicability of AVG experience.
PMID- 28706742
TI - Pulmonary Hemorrhage following Edge-to-Edge Mitral Valve Repair.
AB - Mitral valve repair with the MitraClip device has emerged as an effective
treatment option for patients with severe mitral regurgitation and
contraindications for surgical interventions. While the procedure is not known to
cause pulmonary complications, we describe two cases of pulmonary hemorrhage
following percutaneous mitral valve repair. The patients did well with supportive
care and reinitiation of anticlotting agents was well tolerated after resolution
of bleeding.
PMID- 28706741
TI - The Link between Depression and Chronic Pain: Neural Mechanisms in the Brain.
AB - Chronic pain, as a stress state, is one of the critical factors for determining
depression, and their coexistence tends to further aggravate the severity of both
disorders. Unfortunately, their association remains unclear, which creates a
bottleneck problem for managing chronic pain-induced depression. In recent years,
studies have found considerable overlaps between pain- and depression-induced
neuroplasticity changes and neurobiological mechanism changes. Such overlaps are
vital to facilitating the occurrence and development of chronic pain and chronic
pain-induced depression. In this review, we summarized the role of
neuroplasticity in the occurrence and development of the two disorders in
question and explored individualized application strategies of analgesic drugs
and antidepressants that have different pharmacological effects in the treatment
of chronic pain-induced depression. Therefore, this review may provide new
insights into the understanding of association between chronic pain and
depression.
PMID- 28706743
TI - When Is the Optimal Timing of Surgical Intervention for Severe Functional
Tricuspid Regurgitation?
AB - Functional tricuspid regurgitation (TR) is a serious pathology to be noted for
severe right heart failure (HF) and poor prognosis; however, the conventional
assessment of TR has some limitations and the optimal timing of surgical
intervention remains unclear. A 79-year-old Japanese female was admitted to our
hospital to undergo cardiac surgery, because edema gradually got worse despite
the increase in diuretics. She had a history of atrial fibrillation (AF) and
chronic HF due to severe TR and had been treated with a furosemide for leg edema
4 years ago. A transthoracic echocardiogram (TTE), transesophageal
echocardiogram, cardiac magnetic resonance imaging, and cardiac pool scintigraphy
demonstrated severe functional TR with tricuspid annular dilation, insufficient
tricuspid valve coaptation, and reduced right ventricular ejection fraction (EF)
but preserved left ventricular EF. In addition, Swan-Ganz catheter study showed
normal pulmonary arterial wedge pressure and mean pulmonary arterial pressure.
Tricuspid ring annuloplasty was performed with MC3 ring. Postoperative TTE showed
trivial TR, and she had no edema with normal sinus rhythm two months later.
Annuloplasty to severe functional TR caused by tricuspid annular dilation due to
AF dramatically improved right HF. Cardiologist should pay strict attention to
the optimal timing of surgical intervention for TR.
PMID- 28706744
TI - Management of Oromandibular Dystonia: A Case Report and Literature Update.
AB - Oromandibular dystonia (OMD) is a movement disorder characterized by involuntary,
paroxysmal, and patterned muscle contractions of varying severity resulting in
sustained spasms of masticatory muscles, affecting the jaws, tongue, face, and
pharynx. It is most commonly idiopathic or medication-induced, but peripheral
trauma sometimes precedes the condition. We present a case report of a 26-year
old female patient who suffered repetitive bouts of hemifacial muscle
contractions for 2 years on closing the mouth which interfered in patient's well
being and quality of life by hampering her ability to eat and talk and to the
extent of inability to breath due to contractions of her neck muscles. Prompt
diagnosis of a chronic oromandibular dystonia jaw closing type led to the control
of the spasmodic muscle contractions within 24 hours and alleviation of patients
fear of morbidity.
PMID- 28706745
TI - Acute Esophageal Necrosis in an Alcoholic after Successful Resuscitation from
Cardiac Arrest.
AB - INTRODUCTION: We present a patient who presented to the ICU after successful
resuscitation from cardiac arrest who was subsequently diagnosed with AEN. CASE
PRESENTATION: A 66-year-old female presented after cardiac arrest in which return
of spontaneous circulation was achieved within 7 minutes after the initiation of
CPR. She was intubated on the scene and found to have coffee ground emesis in her
bathroom when found unresponsive. Due to the hemodynamically significant GI
bleed, patient was started on IV proton pump inhibitor, octreotide, and levophed.
Subsequent endoscopy showed diffuse severe mucosal changes characterized by
blackness, erythema, friability, granularity, inflammation, and decreased
vascular pattern in the middle third of the esophagus and in the lower third of
the esophagus. DISCUSSION: AEN is a rare syndrome with a prevalence ranging from
0.001 to 0.2% of EGD. This patient is especially rare as this patient was female
and had AEN in the middle esophagus along with lower esophagus. The
pathophysiology in this patient is hypothesized that she had cardiac arrest
secondary to acute upper GI hemorrhage. Subsequent low-flow state (cardiac
arrest) in addition to being in the setting of severe alcohol abuse led to
esophageal necrosis.
PMID- 28706746
TI - Acute Pancreatitis and Rhabdomyolysis with Acute Kidney Injury following Multiple
Wasp Stings.
AB - Multiple wasp stings can induce multiple organ dysfunction by toxic reactions.
However, acute pancreatitis is a rare manifestation in wasp sting injury. A 74
year-old woman visited the emergency department by anaphylactic shock because of
multiple wasp stings. Acute kidney injury, rhabdomyolysis, hepatotoxicity, and
coagulopathy were developed next day. Serum amylase and lipase were elevated and
an abdominal computed tomography revealed an acute pancreatitis. Urine output was
recovered after 16 days of oliguria (below 500 ml/day). Her kidney, liver, and
pancreas injury gradually improved after sessions of renal replacement therapy.
PMID- 28706747
TI - Adrenal Rest Tumor of the Liver Preoperatively Diagnosed as Hepatocellular
Carcinoma.
AB - BACKGROUND: Hepatic adrenal rest tumors are rare and show similar findings to
hepatocellular carcinoma (HCC). It is difficult to distinguish an adrenal rest
tumor from HCC due to radiological similarity. We report a case of an adrenal
rest tumor in the liver that mimicked HCC radiologically. CASE PRESENTATION: A 67
year-old female was referred to our hospital due to the finding of a hepatic
mass. Enhanced computed tomography revealed a 17 mm well-defined tumor that was
enhanced in the arterial phase and washed out in the portal and delayed phase in
the posterosuperior subsegment of the right hepatic lobe, and HCC was suspected.
We performed a subsegmental resection of the liver. Microscopic findings showed
that the tumor was composed of pale cells, and tumor cells were aligned in
alveolar or fascicular arrangements in a similar manner to features of
adrenocortical tissue. Immunohistochemically, the tumor expressed synaptophysin
and CD56. The final histopathologic diagnosis in this case was an adrenal rest
tumor of the liver. CONCLUSIONS: An adrenal rest tumor is similar to HCC in
radiological findings. This hepatic tumor should be added to the list of
radiological differential diagnoses of hypervascular hepatic tumors.
PMID- 28706748
TI - Comparison of Globus Pallidus Interna and Subthalamic Nucleus in Deep Brain
Stimulation for Parkinson Disease: An Institutional Experience and Review.
AB - Deep Brain Stimulation (DBS) has revolutionized the lives of patients of
Parkinson disease, offering therapeutic options to those not benefiting entirely
from medications alone. With its proven track record of outperforming the best
medical management, the goal is to unlock the full potential of this therapy.
Currently, the Globus Pallidus Interna (GPi) and Subthalamic Nucleus (STN) are
both viable targets for DBS, and the choice of site should focus on the
constellation of symptoms, both motor and nonmotor, which are key determinants to
quality of life. Our article sheds light on the specific advantages and drawbacks
of the two sites, highlighting the need for matching the inherent properties of a
target with specific desired effects in patients. UT Southwestern Medical Center
has a robust and constantly evolving DBS program and the narrative from our
center provides invaluable insight into the practical realities of DBS. The
ultimate decision in selecting a DBS target is complex, ideally made by a
multidisciplinary team, tailored towards each patient's profile and their
expectations, by drawing upon scientific evidence coupled with experience.
Ongoing research is expanding our knowledge base, which should be dynamically
incorporated into an institute's DBS paradigm to ensure that patients receive the
optimal therapy.
PMID- 28706749
TI - Memories of John Fahey and His Contributions to the Multicenter AIDS Cohort Study
(MACS).
AB - John Fahey was an integral member of the small group of investigators who
developed the Multicenter AIDS Cohort Study (MACS) in the early 1980s. A major
research theme in the MACS was defining immune system changes in men at risk for
developing AIDS. John's experience and expertise provided a solid grounding for
the immunologic investigations conducted in the MACS. Additionally, he
contributed enormously to the science of the MACS and pioneered the critical
evaluation of serologic methods of documenting infection with HIV and T cell
phenotyping. Perhaps most importantly, John recruited key new investigators to
the MACS, and worked closely with the original MACS investigators to create a
structure that promoted scientific innovation, openness, and the ability to
quickly respond to emerging research themes.
PMID- 28706750
TI - A Reduced Set of Features for Chronic Kidney Disease Prediction.
AB - Chronic kidney disease (CKD) is one of the life-threatening diseases. Early
detection and proper management are solicited for augmenting survivability. As
per the UCI data set, there are 24 attributes for predicting CKD or non-CKD. At
least there are 16 attributes need pathological investigations involving more
resources, money, time, and uncertainties. The objective of this work is to
explore whether we can predict CKD or non-CKD with reasonable accuracy using less
number of features. An intelligent system development approach has been used in
this study. We attempted one important feature selection technique to discover
reduced features that explain the data set much better. Two intelligent binary
classification techniques have been adopted for the validity of the reduced
feature set. Performances were evaluated in terms of four important
classification evaluation parameters. As suggested from our results, we may more
concentrate on those reduced features for identifying CKD and thereby reduces
uncertainty, saves time, and reduces costs.
PMID- 28706751
TI - Development and Implementation of a Coagulation Factor Testing Method Utilizing
Autoverification in a High-volume Clinical Reference Laboratory Environment.
AB - BACKGROUND: Testing coagulation factor activities requires that multiple
dilutions be assayed and analyzed to produce a single result. The slope of the
line created by plotting measured factor concentration against sample dilution is
evaluated to discern the presence of inhibitors giving rise to nonparallelism.
Moreover, samples producing results on initial dilution falling outside the
analytic measurement range of the assay must be tested at additional dilutions to
produce reportable results. METHODS: The complexity of this process has motivated
a large clinical reference laboratory to develop advanced computer algorithms
with automated reflex testing rules to complete coagulation factor analysis. A
method was developed for autoverification of coagulation factor activity using
expert rules developed with on an off the shelf commercially available data
manager system integrated into an automated coagulation platform. RESULTS: Here,
we present an approach allowing for the autoverification and reporting of factor
activity results with greatly diminished technologist effort. CONCLUSIONS: To the
best of our knowledge, this is the first report of its kind providing a detailed
procedure for implementation of autoverification expert rules as applied to
coagulation factor activity testing. Advantages of this system include ease of
training for new operators, minimization of technologist time spent, reduction of
staff fatigue, minimization of unnecessary reflex tests, optimization of
turnaround time, and assurance of the consistency of the testing and reporting
process.
PMID- 28706752
TI - Rationale of Using Dynamic Imaging for Characterization of Suspicious Lung Masses
into Benign or Malignant on Contrast Enhanced Multi Detector Computed Tomography.
AB - OBJECTIVES: To assess the utility of dynamic imaging namely, wash-in and wash-out
characteristics through multidetector contrast-enhanced computed tomography in
differentiating benign and malignant pulmonary masses. MATERIALS AND METHODS:
Seventy-three patients who were suspected to have malignant pulmonary mass on the
basis of clinical symptoms and chest radiograph were included in the study. All
the patients underwent multidetector computed tomography scanning, and three
series of images were obtained for each patient-noncontrast, early enhanced, and
15 min delayed enhanced scans. Computed tomography (CT) findings were assessed in
terms of washin, absolute, and relative percentage washout of contrast. Biopsy of
the mass was done and sent for histopathological evaluation. Sensitivity,
specificity, and area under curve for diagnosing malignancy in the lung masses
were calculated by considering both the wash-in and wash-out characteristics at
dynamic CT and plotting the receiver operating curve after the final diagnosis
which was obtained by histopathological evaluation. RESULTS: Threshold net
enhancement (washin) value of >22.5 HU had sensitivity, specificity, and
diagnostic accuracy of 88.5%, 57.1%, and 82%, respectively, in predicting
malignancy. Threshold relative percentage washout of <16.235% had 98.1%, 85.7%,
and 94% sensitivity, specificity, and diagnostic accuracy, respectively, and
threshold absolute percentage washout of <42.72% had 98.1%, 95.2%, and 95%
sensitivity, specificity, and diagnostic accuracy, respectively, in predicting
malignancy. CONCLUSION: Threshold net enhancement (washin), absolute and relative
washout percentages can be used to predict malignancy with very high diagnostic
yield, and possibly obviate the need of invasive procedures for diagnosis of
bronchogenic carcinoma.
PMID- 28706753
TI - Evaluation of Institute of Medicine Guidelines for Gestational Weight Gain in
Women with Chronic Hypertension.
AB - Objective To assess the impact of gestational weight gain (GWG) outside the
Institute of Medicine (IOM) recommendations on perinatal outcomes in pregnancies
complicated by chronic hypertension (HTN). Methods The study consisted of a
retrospective cohort of all singletons with HTN from 2000 to 2014. Maternal
outcomes examined were superimposed preeclampsia and cesarean delivery. Neonatal
outcomes were small for gestational age (SGA), large for gestational age (LGA),
and preterm birth (PTB). Groups were compared using analysis of variance and chi
squared test for trend. Backward stepwise logistic regression was adjusted for
confounding factors. Results Of 702 subjects, 106 (15.1%) gained within, 176
(25.0%) gained less, and 420 (59.8%) gained more weight than the IOM
recommendations. After adjusting for confounders, GWG above IOM recommendations
remained associated with LGA (adjusted odds ratio [AOR]: 2.53, confidence
interval [CI] 95%:1.29-4.95). Weight gain less than recommended was associated
with a decreased risk of superimposed preeclampsia (AOR: 0.49, CI 95%: 0.26-0.93)
without increasing the risk of SGA (AOR: 1.03, CI 95%: 0.57-1.86). Conclusion
Women with pregnancies complicated by chronic HTN should be counseled regarding
the association of LGA with excessive GWG. Additionally, they should be counseled
that weight gain below recommendations may be associated with a decreased risk of
superimposed preeclampsia; however, this association deserves further
investigation.
PMID- 28706754
TI - Smart Release Nano-formulation of Cytochrome C and Hyaluronic Acid Induces
Apoptosis in Cancer Cells.
AB - Herein we tested a nanosized cancer-cell targeted delivery system based on
cytochrome c (Cyt c) and hyaluronic acid. Cyt c was chosen since it is a per se
non-toxic protein but causes apoptosis when delivered to the cytoplasm of target
cells. Hyaluronic acid was employed to create the nanosized delivery system with
passive targeting capability in order to exploit the enhanced permeation and
retention (EPR) effect and active targeting capability of hyaluronic acid. In
addition, our goal was to incorporate a smart release strategy to only promote
protein release upon reaching its target. Nanoparticles were formed by a simple
yet precise nanoprecipitation process based on desolvation. They were physically
characterized to select precipitation conditions leading to adequate size, shape,
protein bioactivity, and protein loading to produce a feasible targeted cancer
treatment. We synthesized nanoparticles of around 500 nm diameter with a 60%
protein loading and more than 80% of protein bioactivity. In vitro, cumulative
release of 92% of Cyt c was observed after 8 h under conditions mimicking the
reductive intracellular environment, while under non-denaturing conditions only
20% was released. The nanoparticles displayed a selective cytotoxic effect on
cancer cells. After 6 h of incubation with the nanoparticles, hyaluronic acid
receptor over expressing A549 human lung adenocarcinoma cells showed a viability
of ca. 20% at 0.16 mg/ml of Cyt c concentration. Only a negligible effect was
observed on viability of COS-7 African green monkey kidney fibroblast, a normal
cell line notoverexpressing the hyaluronic acid receptor. Confocal microscopy
confirmed that the drug delivery system indeed delivered Cyt c to the cytoplasm
of the target cells. We conclude that we were able to create a smart stimuli
responsive targeted drug delivery system with significant potential in cancer
therapy.
PMID- 28706755
TI - Effects of a Novel Whitening Formulation on Dental Enamel.
AB - OBJECTIVE: The goal of this study was to evaluate the enamel whitening effects of
2 new test formulations, one of which was a rinse, and the other a whitening
strip. MATERIALS AND METHODS: Forty enamel chips were prepared from 20 healthy
extracted teeth (2 from each tooth). After pre-staining and colorimetry to
measure L* and b* values, 20 matched samples were immersed in either test or
control rinses, and then colorimetry was performed again after 1 hr, 2 hr, 3 hr,
6 hr, 12 hr, 24 hr and 48 hrs (Each hour equates to one month of clinical use at
the recommended dosage of 1 minute exposure 2 times a day). The remaining 20
matched samples were exposed to the test or control whitening strips and
colorimetry was performed every 30 minutes for a total of 10 treatments. RESULTS:
Overall, the whitening performance of test and control strips was similar. The
test and control rinses had a similar lightening effect over the first 3 hours
(equivalent to 3 months of clinical use). Subsequently, the control rinse
continued to lighten samples, whereas the test rinse had little further effect.
CONCLUSION: Test and control-whitening strips showed similar effects; over time
whitening strips showed a greater lightening effect than whitening rinses.
PMID- 28706756
TI - Impact of Vital Dyes on Cell Viability and Transduction Efficiency of AAV Vectors
Used in Retinal Gene Therapy Surgery: An In Vitro and In Vivo Analysis.
AB - PURPOSE: Treatment of inherited retinal degenerations using adeno-associated
viral (AAV) vectors involves delivery by subretinal injection. In the latter
stages, alteration of normal anatomy may cause difficulty in visualizing the
retinotomy, retinal detachment extension, and vector diffusion. Vital dyes may be
useful surgical adjuncts, but their safety and impact on AAV transduction are
largely unknown. METHODS: The effects of Sodium Fluorescein (SF), Membrane Blue
(MB), and Membrane Blue Dual (DB) at a range of dilutions were assessed on human
embryonic kidney cells in vitro using an AAV2-green fluorescent protein (GFP)
reporter at different multiplicities of infection. Flow cytometry analysis was
performed to assess both cell viability and transduction efficiency. The effect
on quantitative (q)PCR titer was determined. Balanced salt solution (BSS) or
dilute DB (1:5 in BSS) were delivered subretinally into left/right eyes of
C57BL/6J mice (n = 12). Retinal structure and function were analyzed by optical
coherence tomography, autofluorescence, dark-and light-adapted full-field
electroretinography. RESULTS: DB and MB were not toxic at any concentration
tested, SF only when undiluted. The presence of dyes did not adversely affect the
genomic titer. DB even increased the values, due to presence of surfactant in the
formulation. AAV2-GFP transduction efficiency was not reduced by the dyes. No
structural and functional toxic effects were observed following subretinal
delivery of DB. CONCLUSIONS: Only undiluted SF affected cell viability. No
effects on qPCR titer and transduction efficiency were observed. DB does not
appear toxic when delivered subretinally and improves titer accuracy. DB may
therefore be a safe and helpful adjunct during gene therapy surgery.
TRANSLATIONAL RELEVANCE: This paper might be of interest to the retinal gene
therapy community: it is a "bench to bedside" research paper about the potential
use of dyes as a surgical adjunct during the gene therapy surgery. We have tested
the potential toxicity and impact on transduction efficiency in an in vitro and
in vivo model.
PMID- 28706757
TI - Biological Involvement of MicroRNAs in Proliferative Vitreoretinopathy.
AB - Even with a high surgical success rate for retinal detachment and proliferative
vitreoretinopathy (PVR) supported by the robust improvement in vitrectomy surgery
and its related devices, certain questions still remain for the pathogenesis and
treatment of PVR. One of the important biological events in PVR is epithelial
mesenchymal transition (EMT) of the retinal pigment epithelial (RPE) cells.
MicroRNAs are noncoding, small, single-strand RNAs that posttranscriptionally
regulate gene expression and have essential roles in homeostasis and pathogenesis
in many diseases. Recently, microRNAs also had a critical role in EMT in many
tissues and cells. One main purpose of this brief review is to describe the
knowledge obtained from microRNA research, especially concerning vitreoretinal
diseases. In addition, the potential role of microRNAs in prevention of PVR by
regulating EMT in RPE cells is described. Understanding microRNA involvement in
PVR could be helpful for developing new biological markers or therapeutic targets
and reducing the rate of visual disability due to PVR.
PMID- 28706758
TI - Solution-Based Fabrication of Polycrystalline Si Thin-Film Transistors from
Recycled Polysilanes.
AB - Currently, research has been focusing on printing and laser crystallization of
cyclosilanes, bringing to life polycrystalline silicon (poly-Si) thin-film
transistors (TFTs) with outstanding properties. However, the synthesis of these
Si-based inks is generally complex and expensive. Here, we prove that a
polysilane ink, obtained as a byproduct of silicon gases and derivatives, can be
used successfully for the synthesis of poly-Si by laser annealing, at room
temperature, and for n- and p-channel TFTs. The devices, fabricated according to
CMOS compatible processes at 350 degrees C, showed field effect mobilities up to
8 and 2 cm2/(V s) for n- and p-type TFTs, respectively. The presented method
combines a low-cost coating technique with the usage of recycled material,
opening a route to a convenient and sustainable production of large-area,
flexible, and even disposable/single-use electronics.
PMID- 28706759
TI - Mild and Selective Protein Release of Cell Wall Deficient Microalgae with Pulsed
Electric Field.
AB - Pulsed electric field (PEF) is considered to be a very promising technology for
mild cell disruption. The application of PEF for microalgae that have a rigid
cell wall, however, is hampered by the presence of that rigid outer cell wall. A
cell wall free mutant of C. reinhardtii was used to mimic pretreated microalgae
with removed cell wall, to investigate the possibility of using PEF for protein
release from microalgae. A complete release of hydrophilic proteins from the cell
wall free mutants was observed whereas PEF treatment on the cell wall containing
species resulted in substantially lower protein yields. Additional experiments
showed that even at low energy input (0.05 kWh/kgbiomass), still about 70% of the
proteins could be released with respect to bead beating as reference. These
released proteins were water-soluble while the hydrophobic chlorophyll remained
mainly entrapped in cell particles. SEM-analysis of these cell particles showed
that PEF only opened the cells, instead of completely fragmenting them into
smaller particles. These results indicate that PEF is an energy-efficient cell
disruption method for selective release of water-soluble proteins, after the
microalgal outer cell wall is removed. Enzymatic pretreatment to degrade the cell
walls before PEF treatment was shown to be an efficient method to remove the cell
wall.
PMID- 28706760
TI - Bactericidal Effect of Different Anti-Microbial Agents on Fusobacterium Nucleatum
Biofilm.
AB - INTRODUCTION: The root canal anatomy of the teeth is very complex. Complete
debridement of the root canals is a challenge and is very important for the
success of the root canal treatment. Hence, this study was done to find an
effective irrigant which can be used during root canal treatment. OBJECTIVE: The
bactericidal effect of a potential root canal irrigant was compared with two
commonly used root canal irrigants against monoculture biofilm of a commercially
available isolate of Fusobacterium nucleatum. METHODS: A monoculture biofilm of
Fusobacterium nucleatum was grown on glass slides. The glass slides containing
the biofilm were immersed in centrifuge tubes containing 5% sodium hypochlorite,
2% Chlorhexidine, 6% turmeric solution, 9% turmeric solution and distilled water
for a time span of one minute. A wire loop was used to scrape off the biofilms
onto sterile brain heart infusion agar plates. This was further subjected to an
incubation period of 96 hours at 37 degrees C. Colony forming units were
quantified by statistical analysis and results were obtained. RESULTS: The anti
bacterial activity of 6% and 9% turmeric solution was statistically significant
against Fusobacterium nucleatum when compared to 2% Chlorhexidine and 5% sodium
hypochlorite. CONCLUSION: In endodontic treatment, turmeric solution may be
considered as an effective irrigant.
PMID- 28706761
TI - Rapidly Fatal Radiation-induced Glioblastoma.
AB - Glioblastoma (GBM) typically occurs as a primary tumour (i.e., primary GBM) and
predominantly affects elderly patients. The remaining ~10% occur as a result of
malignant progression from lower grade astrocytic tumours (i.e., secondary GBM).
Although there are no certain causative environmental agents, prior radiation
exposure may play a role. We report on a patient who had been treated six years
prior for a vestibular schwannoma with high-dose conventional radiotherapy and
subsequently developed a rapidly fatal glioblastoma at the same location. The
diagnosis was confirmed by routine histopathology as well as more advanced
techniques, such as whole genome copy number analysis.
PMID- 28706762
TI - Metastatic Breast Cancer with BRCA Mutation Discovered By Next-Generation
Sequencing Responding to Olaparib.
AB - Breast cancer susceptibility genes 1 and 2 (BRCA1 and BRCA2) mutations are
associated with hereditary breast and ovarian cancer syndromes (HBOC). However,
certain individuals with breast cancer do not meet high-risk factors for
hereditary breast cancer screening based on age, family history, and biology of
malignancy. We present a patient with relapsed breast cancer who developed
progressive disease with significant tumor burden causing a recurrent pleural
effusion. Next-generation sequencing (NGS) done on a tumor biopsy was positive
for the BRCA2 mutation. Olaparib was initiated with a resolution of the pleural
effusion and a significant decrease in the size of the malignant lymphadenopathy
and pulmonary lesions. There are numerous reports of comprehensive molecular
profiling improving access to therapy, most notably for lung cancer, as well as
melanoma. However, this has not been widely utilized for breast cancer. However,
in our case, NGS provided our patient with an effective therapy and should be
considered for the future management of metastatic breast cancer.
PMID- 28706763
TI - Comparison of Knowledge, Attitudes, and Practices of Educated and Uneducated
Adults Regarding Human Immunodeficiency Virus in Karachi, Pakistan.
AB - BACKGROUND: Despite the high prevalence of human immunodeficiency virus (HIV) in
Pakistan, no prior work has been done to specifically highlight the importance of
education as a social vaccine against HIV. Therefore, our study focuses on
differences in knowledge and practices regarding HIV and acquired
immunodeficiency syndrome (AIDS) among educated and uneducated adults.
METHODOLOGY: A cross-sectional study was carried out in which data was collected
from all over Karachi. An individual was designated as educated if he had
received education above primary school level. Individuals who had studied till
primary school or less were considered uneducated. The questionnaire was split
into four sections that assessed respondents' demographics, knowledge, attitudes,
and practices regarding HIV/AIDS. Chi square test was used as the primary
statistical test. RESULTS: Out of the 446 adult participants, 235 (52.7%) were
educated and 211 (47.3%) were uneducated. Educated participants were
significantly more likely to have heard about HIV (183 vs. 39, p < 0.001) and had
better knowledge about the symptoms of HIV/AIDS (p < 0.001). Among the
participants who knew about AIDS, a greater percentage of uneducated (n = 28,
53%) than educated individuals (n = 68, 37%) believed that people suffering from
AIDS should be isolated (p = o.o16) and that HIV can spread through water (40% vs
20% respectively, p < 0.001). Both educated (n = 49, 27%) and uneducated (n = 46,
89%) adults believed that awareness would help prevent the spread of HIV (p =
0.978) and were willing to educate their children about it (p = 0.696).
CONCLUSION: Our study revealed a gap in the knowledge about HIV/AIDS between
educated and uneducated adults. There is an urgent need for awareness programs
that especially reach out to the uneducated masses that are otherwise uninformed
about HIV and are under high risk of acquiring HIV.
PMID- 28706764
TI - Neuroradiological Endovascular Intervention for Diplopia in a Case of Aneurysmal
Aberrant Regeneration of the Third Nerve.
AB - Aberrant regeneration of the third nerve occurs as a result of synkinetic
'miswiring' of the third nerve following its injury, such as in third cranial
nerve palsy due to tumor, trauma, or aneurysm. The case presented is an elderly
woman with new vertical diplopia, which led to a diagnosis of a third cranial
nerve palsy, thought to be caused by a 5 mm blister aneurysm of the posterior
communicating artery. However, neuro-ophthalmological evaluation diagnosed
aberrant regeneration of the third nerve, with the cause of her new vertical
diplopia being an ipsilateral fourth nerve palsy. The patient underwent
endovascular treatment of her aneurysm using stent-assisted coiling. This
procedure was complicated by an episode of air embolism, from which the patient
made a good recovery. This patient's presentation demonstrates that the cause of
any diplopia must be established, and presents a novel, semi-schematic
illustration of aberrant regeneration of the third nerve that should aid
clinicians in its recognition.
PMID- 28706765
TI - Trauma and Hypothermia in Antarctica: An Emergency Medicine Marine Simulation
Scenario.
AB - Simulation has been shown to improve both learner knowledge and patient outcomes.
Many emergency medicine training programs incorporate simulation into their
curricula to provide learners with experiences that are rare to encounter in
practice, yet performance with a high degree of competence is critical. One rare
encounter, which is depicted in the report, is the management of a trauma patient
who was hypothermic after falling from an expedition vessel into the cold
Southern Ocean. The unique scenario presented in this technical report
incorporates CanMEDS learning objectives including the communicator, health
advocate, and collaborator roles. Using medical simulation facilities, marine
performance simulation facilities, and a video, this scenario provides teaching
that is uncommon in traditional emergency medicine training. As such, it is
valuable for trainees who intend to practice rural, remote, or expedition
medicine, or provide coverage for ships and marine installations.
PMID- 28706766
TI - A Case-Based Review of the Management of Penetrating Brain Trauma.
AB - Principles of penetrating head trauma management were established by Harvey
Cushing in relation to the management of penetrating brain injuries of World War
One. Cushing radically debrided the scalp and skull and aggressively irrigated
wound tracks to remove foreign bodies. He would then obtain water-tight closure.
Cushing significantly decreased infection rates which reportedly limited the
major cause of mortality due to penetrating head injuries. Many advances have
been made by contributions from World War Two, Korean War, Vietnam War, and
Iran/Iraq conflicts. Early radical decompression, with conservative debridement
and duraplasty applied to blast-induced penetrating injuries during Operation
Iraqi Freedom, has resulted in increased survivability and neurological
improvement. Each advance in the management of these injuries is based upon more
effectively addressing one or more components of Matson's tenets. This case
series reviews the successful management of three patients that presented to a
level I trauma center with a penetrating head injury from high-velocity
projectiles. Management principles of each patient begin with a proper patient
assessment, application of Matson's tenets from the time of injury, and airway
control. Surgical management is based upon adherence to Grahm's Guidelines which
emphasize criteria centered upon post-resuscitative Glasgow Coma Scale score and
appropriate imaging. This case series suggests that proper patient evaluation,
adherence to Matson's tenets and to Grahm's Guidelines, and appropriate patient
selection for operative management leads to improved survival of patients with
penetrating head trauma from high-velocity projectiles.
PMID- 28706767
TI - Surgical Excision of a Symptomatic Thoracic Nerve Root Perineural Cyst Resulting
in Complete Resolution of Symptoms: A Case Report.
AB - Tarlov (perineural) cysts of the nerve root are common and usually incidental
findings during magnetic resonance imaging (MRI) of the lumbosacral spine. There
are a few case reports where symptomatic thoracic perineural cysts have been
described in the literature. We report a case of a high thoracic nerve root
perineural cyst that failed conservative therapy, requiring surgical
intervention. Our patient presented with radicular symptoms involving the left
hand. Imaging workup revealed a cystic lesion of the left T1 nerve root at the
level of the foramen. Surgical resection resulted in significant improvement in
patient symptoms, and pathology revealed a perineural cyst. We conclude that a
thoracic perineural (Tarlov) cyst can be symptomatic by causing nerve root
compression and can be mistaken as a nerve root sheath tumor on imaging. Surgical
treatment can be curative.
PMID- 28706769
TI - Differential item functioning magnitude and impact measures from item response
theory models.
AB - Measures of magnitude and impact of differential item functioning (DIF) at the
item and scale level, respectively are presented and reviewed in this paper. Most
measures are based on item response theory models. Magnitude refers to item level
effect sizes, whereas impact refers to differences between groups at the scale
score level. Reviewed are magnitude measures based on group differences in the
expected item scores and impact measures based on differences in the expected
scale scores. The similarities among these indices are demonstrated. Various
software packages are described that provide magnitude and impact measures, and
new software presented that computes all of the available statistics conveniently
in one program with explanations of their relationships to one another.
PMID- 28706768
TI - DNA-PK and P38 MAPK: A Kinase Collusion in Alzheimer's Disease?
AB - The pathogenesis of Alzheimer's disease (AD), characterized by prevalent neuronal
death and extracellular deposit of amyloid plaques, is poorly understood. DNA
lesions downstream of reduced DNA repair ability have been reported in AD brains.
Neurons predominantly use a mechanism to repair double-strand DNA breaks (DSB),
which is non-homologous end joining (NHEJ). NHEJ requires DNA-dependent protein
kinase (DNA-PK) activity. DNA-PK is a holoenzyme comprising the p460 kD catalytic
subunit (DNA-PKcs) and its activator Ku, a heterodimer of p86 and p70 subunits.
Ku first binds and then recruits DNA-PKcs to double-stranded DNA ends before NHEJ
process begins. Studies have shown reduced NHEJ activity as well as DNA-PKcs and
Ku protein levels in AD brains suggesting possible contribution of unrepaired DSB
to AD development. However, normal aging brains also show reduced DNA-PKcs and Ku
levels thus challenging the notion of any direct link between NHEJ and AD.
Another kinase, p38 MAPK is induced by various DNA damaging agents and DSB
itself. Increased DNA damage with aging could induce p38 MAPK and its induction
may be sustained when DNA repair is compromised in the brain with reduced DNA-PK
activity. Combined, these two events may potentially set the stage for an awry
nervous system approaching AD.
PMID- 28706770
TI - Open globe injury with an interesting intra-ocular foreign body.
AB - Introduction: Cases of penetrating ocular trauma due to osseous material are
limited, so reported incidents are valuable in determining outcomes and proper
treatment courses. Case description: We report a case of an open globe injury of
the left eye with an intraocular foreign body occurring after a firework exploded
in the hand of a 22-year-old man. The patient presented with light perception
vision in the injured eye with a full-thickness limbal laceration and dense
hyphema obscuring fundoscopy. CT scan revealed a hyperdense foreign body
juxtaposed to the lens. Immediate surgical intervention to repair the globe
rupture revealed a defect in the anterior capsule and small, white objects in the
posterior chamber that were promptly removed. Pathologic investigation determined
these fragments to be cortical bone likely from the patient's phalanges. Results
and discussion: There was no evidence of endophthalmitis or keratitis from time
of injury to the five-month follow-up, suggesting that the risk of infection may
be low and therefore it may be reasonable to manage these injuries with a period
of observation.
PMID- 28706771
TI - An unusual case of bilateral anterior uveitis related to moxifloxacin: the first
report in Latin America.
AB - Objective: To report a case of bilateral anterior uveitis secondary to oral
moxifloxacin. Methods: Case report. Results: A 54-year-old female presented
bilateral anterior uveitis following a 10-day course of oral moxifloxacin. She
developed a bilateral anterior uveitis associated with pigment dispersion
syndrome and iris transillumination. Conclusions: Drug-induced uveitis is one of
the causes of anterior uveitis. Uveitis related to fluoroquinolones is a rare
entity, there are few cases reported in the literature, this is the first case
reported in Latin America.
PMID- 28706772
TI - Dorsal skinfold chamber models in mice.
AB - Background/purpose: The use of dorsal skinfold chamber models has substantially
improved the understanding of micro-vascularisation in pathophysiology over the
last eight decades. It allows in vivo pathophysiological studies of
vascularisation over a continuous period of time. The dorsal skinfold chamber is
an attractive technique for monitoring the vascularisation of autologous or
allogenic transplants, wound healing, tumorigenesis and compatibility of
biomaterial implants. To further reduce the animals' discomfort while carrying
the dorsal skinfold chamber, we developed a smaller chamber (the Leipzig Dorsal
Skinfold Chamber) and summarized the commercial available chamber models. In
addition we compared our model to the common chamber. Methods: The Leipzig Dorsal
Skinfold Chamber was applied to 66 C57Bl/6 female mice with a mean weight of 22
g. Angiogenesis within the dorsal skinfold chamber was evaluated after injection
of fluorescein isothiocyanate dextran with an Axio Scope microscope. The mean
vessel density within the dorsal skinfold chamber was assessed over a period of
21 days at five different time points. The gained data were compared to previous
results using a bigger and heavier dorsal skinfold model in mice. A PubMed and a
patent search were performed and all papers related to "dorsal skinfold chamber"
from 1st of January 2006 to 31st of December 2015 were evaluated regarding the
dorsal skinfold chamber models and their technical improvements. The main models
are described and compared to our titanium Leipzig Dorsal Skinfold Chamber model.
Results: The Leipzig Dorsal Skinfold Chamber fulfils all requirements of
continuous in vivo models known from previous chamber models while reducing
irritation to the mice. Five different chamber models have been identified
showing substantial regional diversity. The newly elaborated titanium dorsal
skinfold chamber may replace the pre-existing titanium chamber model used in
Germany so far, as it is smaller and lighter than the former ones. However, the
new chamber does not reach the advantages of already existing chamber models used
in Asia and the US, which are smaller and lighter. Conclusion: Elaborating a
smaller and lighter dorsal skinfold chamber allows research studies on smaller
animals and reduces the animals' discomfort while carrying the chamber. Greater
research exchange should be done to spread the use of smaller and lighter chamber
models.
PMID- 28706773
TI - Why Doesn't Primary Biliary Cholangitis Respond to Immunosuppressive Medications?
AB - PURPOSE OF REVIEW: The purpose of this review is to discuss reasons why
immunosuppressive therapy so far failed in Primary Biliry Cholangitis. RECENT
FINDINGS: Even targeted immunosuppressive therapy seems ineffective or
potentially harmful. SUMMARY: Bile acid-mediated cholangiocyte damage,
facilitated by insufficient bicarbonate secretion, seems to attenuate the anti
inflammatory and anti-fibrotic actions of immunosuppressant and immunomodulatory
drugs in a clinically significant way.
PMID- 28706774
TI - Are Dominant Strictures in Primary Sclerosing Cholangitis a Risk Factor for
Cholangiocarcinoma?
AB - PURPOSE OF REVIEW: Cholangiocarcinoma is a devastating, unpredictable
complication of large duct primary sclerosing cholangitis (PSC), which occurs in
5-15% of patients. The aim of this review is to discuss whether dominant
strictures (DS) occurring in the larger bile ducts in PSC are a risk factor for
the development of cholangiocarcinoma. RECENT FINDINGS: The development of DS is
related to specific genetic polymorphisms affecting the innate immune system and
the microbiome. In a recent study, the mean survival of PSC patients with DS was
much worse (13.7 years) than for those without a DS (23 years). Survival
difference was related to a 26% risk of cholangiocarcinoma, which developed only
in those with DS. Half of the patients with cholangiocarcinoma presented within 4
months of the diagnosis of PSC. In another study, the risk of developing
cholangiocarcinoma was directly related to the presence of underlying IBD,
although this remains controversial. Efforts are being made towards surveying for
cholangiocarcinoma including magnetic resonance imaging, endoscopic surveillance
and serum tumour markers, but so far, an effective surveillance strategy has not
been identified. DS should be treated endoscopically in the setting of symptoms,
and there is limited evidence to suggest this may impact protectively on
progression to cholangiocarcinoma. SUMMARY: It is established that the presence
of symptomatic DS occurring in the larger bile ducts in PSC can be the first
presentation of cholangiocarcinoma. There is an increasing body of evidence that
even when proven to be benign, dominant biliary strictures predispose to the
future development of cholangiocarcinoma. Regular surveillance should be targeted
at this selected high-risk group of PSC patients.
PMID- 28706775
TI - Alcohol Consumption in Concomitant Liver Disease: How Much is Too Much?
AB - PURPOSE OF REVIEW: High consumption of alcohol can lead to cirrhosis. The risk of
a low to moderate consumption of alcohol in the setting of a concurrent liver
disease is less clear. The aim of this review is to sum the evidence on the risk
of adverse outcomes in patients with liver diseases other than alcoholic liver
disease who consume alcohol. RECENT FINDINGS: High alcohol consumption is
strongly associated with adverse outcomes in most liver diseases. For hepatitis
C, some evidence points to an increased risk for fibrosis progression also with
low amounts. For non-alcoholic fatty liver disease, most studies indicate an
inverse association between fibrosis and alcohol consumption, but methodological
limitations reduce inference. SUMMARY: High alcohol consumption is associated
with an increased risk of fibrosis progression and other adverse outcomes, while
less is clear regarding low to moderate consumption. Obtaining high-level
evidence on this topic ought to be the objective of future studies. Currently, an
individual risk profile should be obtained in patients with liver disease who
consume alcohol.
PMID- 28706776
TI - Electrochemistry of Redox-Active Guest Molecules at beta-Cyclodextrin
Functionalized Silicon Electrodes.
AB - Functionalization of silicon-based sensing devices with self-assembled receptor
monolayers offers flexibility and specificity towards the requested analyte as
well as the possibility of sensor reuse. As electrical sensor performance is
determined by electron transfer, we functionalized H-terminated silicon
substrates with beta-cyclodextrin (beta-CD) molecules to investigate the
electronic coupling between these host monolayers and the substrate. A trivalent
(one ferrocene and two adamantyl moieties), redox-active guest was bound to the
beta-CD surface with a coverage of about 10-11 mol/cm2 and an overall binding
constant of 1.5?109 M-1. This packing density of the host monolayers on silicon
is lower than that for similar beta-CD monolayers on gold. The monolayers were
comparable on low-doped p-type and highly doped p++ substrates regarding their
packing density and the extent of oxide formation. Nonetheless, the electron
transfer was more favorable on p++ substrates, as shown by the lower values of
the peak splitting and peak widths in the cyclic voltammograms. These results
show that the electron-transfer rate on the host monolayers is not only
determined by the composition of the monolayer, but also by the doping level of
the substrate.
PMID- 28706777
TI - Using community-based participatory research and organizational diagnosis to
characterize relationships between community leaders and academic researchers.
AB - Sustaining collaborations between community-based organization leaders and
academic researchers in community-engaged research (CEnR) in the service of
decreasing health inequities necessitates understanding the collaborations from
an inter-organizational perspective. We assessed the perspectives of community
leaders and university-based researchers conducting community-engaged research in
a medium-sized city with a history of community-university tension. Our research
team, included experts in CEnR and organizational theory, used qualitative
methods and purposeful, snowball sampling to recruit local participants and
performed key informant interviews from July 2011-May 2012. A community-based
researcher interviewed 11 community leaders, a university-based researcher
interviewed 12 university-based researchers. We interviewed participants until we
reached thematic saturation and performed analyses using the constant comparative
method. Unifying themes characterizing community leaders and university-based
researchers' relationships on the inter-organizational level include: 1) Both
groups described that community-engaged university-based researchers are
exceptions to typical university culture; 2) Both groups described that the
interpersonal skills university-based researchers need for CEnR require a change
in organizational culture and training; 3) Both groups described skepticism about
the sustainability of a meaningful institutional commitment to community-engaged
research 4) Both groups described the historical impact on research relationships
of race, power, and privilege, but only community leaders described its
persistent role and relevance in research relationships. Challenges to community
academic research partnerships include researcher interpersonal skills and
different perceptions of the importance of organizational history. Solutions to
improve research partnerships may include transforming university culture and
community-university discussions on race, power, and privilege.
PMID- 28706778
TI - Evaluation of Healthy2Go: A country store transformation project to improve the
food environment and consumer choices in Appalachian Kentucky.
AB - Rates of obesity and type 2 diabetes in Kentucky's Cumberland Valley region are
among the highest in the United States and limited access to healthy food
contributes to these epidemics. The aim of Healthy2Go (H2G), a country store
transformation project launched by Spread the Health Appalachia (STHA), was to
improve awareness and availability of healthy options in small, rural stores. Ten
country stores participated in H2G and received training and technical assistance
to increase availability and awareness of healthy foods. Stores made inventory
changes; installed point-of-purchase educational and in-store marketing materials
directing shoppers to healthier options; provided nutrition education such as
healthy recipes; and altered the display and location of healthy items. To
measure changes within stores and the potential impact on resident eating and
purchasing habits, STHA used four instruments: a modified version of the
Nutrition Environs Measures Survey - Corner Stores at baseline and follow-up, a
bimonthly store inventory assessment, a final store owner survey, and a Community
Nutrition Survey at baseline (n = 287) and follow-up (n = 281). The stores in the
H2G program (n = 10) had a 40% increase in stocking fresh produce, a 20% increase
in produce variety, and trends towards increasing healthy inventory. During the
same period, surveyed residents reported a statistically significant increase in
the frequency of healthy food consumption. Small store transformation programs
can improve availability of and access to healthy food in rural settings and
influence local purchasing patterns.
PMID- 28706779
TI - Evaluation of modified nasal to oral endotracheal tube switch-For modified alar
base cinching after maxillary orthognathic surgery.
AB - BACKGROUND: Soft tissue changes secondary to Maxillary orthognathic surgery are
many fold. The alar flare is one among them, which affects the appearance of the
patient. Cinch suture has been used to prevent alar flare; but the presence of
anaesthetic tube hinders cinching. So, the study was aimed to assess an efficacy
of modified nasal to oral tube switch technique for modified alar cinching to
prevent alar flare after orthognathic and nasal corrective surgeries. MATERIALS
AND METHODS: Patients were randomly allocated in each group, who underwent
modified alar base cinching with and without nasal to oral tube switch. Changes
in alar base width, upper lip length was measured with Digital Vernier Caliper
and nasolabial angle (Cotg-Sn-Ls) on lateral cephalogram at 1st, 3rd, 6th, and
12th months after surgery. The time taken and ease of tube switch were noted. The
data obtained were tabulated and interpreted using a test of significance.
RESULTS: Study results showed no statistical significant difference in perinasal
soft changes among both groups. But tube switch appears to be beneficial to
prevent alar flare. CONCLUSION: Modified alar base cinching was performed
effectively in patients with a modified tube switch technique. It increased
positive results in comparison with non-shift. The technique of tube switch used
is effective in prevention of alar flare. Because of small sample size and
limited period of follow up, our study suggests multi centre, randomized studies
to know the technical difficulties of tube switch for cinching and aesthetic
results with varying anaesthetist and the surgeon's experience.
PMID- 28706780
TI - Neurosensory evaluation of inferior alveolar nerve after bilateral sagittal split
ramus osteotomy of mandible.
AB - : Mandibular skeletal deformities are mostly corrected by Sagittal Split Ramus
Osteotomy. One of the main complications of Bilateral Sagittal Split Ramus
Osteotomy is impairement of sensory function of Inferior Alveolar Nerve.
OBJECTIVES: To evaluate the occurrence of neurosensory disturbance by comparing
the subjective and objective assessment of neurosensory responses after bilateral
sagittal split ramus osteotomy.To assess the progress of recovery from the first
post operative day till six months. To explain the factors causing neurosensory
disturbances. METHOD: A series of 24 patients with clinically and
radiographically diagnosed mandibular skeletal deformity were treated with
Bilateral Sagittal Split Ramus Osteotomy. For evaluation of the neurosensory
responses, the parameters consist of subjective and objective test in order to
compare the subjective and objective assessment. RESULTS: On the first post
operative day neurosensory disturbances were seen in all the patients. Recovery
of sensation was seen in all the patients at the end of this study. CONCLUSION:
The incidence of functional nerve disturbances is acceptable, since the
progression towards recovery is inevitable. Prolonged neurosensory disturbance is
greatly related to the degree of manipulation of the inferior alveolar nerve.
PMID- 28706781
TI - Assessment of condyle, masseter and temporal muscles volumes in patients with
juvenile systemic lupus erythematosus: A cross-sectional study.
AB - AIMS: The purpose of this study was to evaluate the effect of the corticosteroid
therapy for both treatment of juvenile systemic lupus erythematosus and disease
activity on two masticatory muscles and condyle of the temporomandibular joint.
METHODS: A total of 21 controls and 48 juvenile systemic lupus erythematosus
patients were investigated. Volumes of the temporal and masseter muscles and
condyle of the subjects were assessed by using a 3D reconstruction in magnetic
resonance imaging. The ITK-SNAP, a medical imaging software, was used for 3D
reconstruction. A dental examination with registration of occlusion was performed
in subjects. Data were statistically analyzed by means of the Dahlberg's test
associated with paired t-test, Fisher's exact test and Chi-square. RESULTS: There
was a positive correlation between temporalis muscle and age (p = 0.032),
masseter volume (p = 0.029) and condyle volume (p = 0.013). The mean volume
measurements of temporal and masseter muscles and condyle were not statistically
associated with juvenile systemic lupus erythematosus regarding disease activity
and corticosteroid therapy (p > 0.05). There were no significant differences
between malocclusion and volume of muscles and condyle. CONCLUSION: This study
suggested that volume of the target structures has no correlation with cumulative
corticosteroid dose, disease activity, and malocclusion.
PMID- 28706782
TI - Immunohistochemical evaluation of podoplanin in odontogenic tumours & cysts using
anti-human podoplanin antibody.
AB - BACKGROUND: Odontogenic Cysts & tumors originate through some aberration from the
normal pattern of odontogenesis. Ameloblastoma is one of the most frequent
intraosseous odontogenic tumors. However it is no longer appropriate to use the
diagnosis of ameloblastoma without specifying the type. Varied-clinical entities
of ameloblastoma differ in their biologic behaviour. Odontogenic cysts like
dentigerous and radicular cysts are less aggressive in nature than odontogenic
tumors. Recently, podoplanin commonly used as a lymphatic endothelial marker in
cancers has recently been found to play a possible role in odontogenic
tumorigenesis also. Therefore the purpose of this study was to
immunohistochemically analyse the expression of podoplanin in ameloblastomas,
KCOTs, dentigerous cysts, radicular cysts & dental follicles. METHODS: Paraffin
embedded tissue specimens of 15 Ameloblastomas (7 follicular, 6 unicystic, 2
desmoplastic),10KCOTs, 5 dentigerous cysts, 5 radicular cysts & 5 dental
follicles were immunohistochemically examined using antibody against podoplanin.
RESULTS: All ameloblastomas displayed podoplanin expression in ameloblast-like
cells of the epithelial islands while the stellate-reticulum like cells exhibited
no or weak immunostaining. Expression of podoplanin in KCOTs was strongly
positive in the cells of the basal and suprabasal layers & odontogenic epithelial
nests. Positive immunoreaction for podoplanin was observed in the inflammatory
radicular cysts and inflamed dentigerous cyst only and negative or weak
expression in the lining epithelium of uninflamed dentigerous cysts and dental
follicles. CONCLUSION: Our results suggest that podoplanin can be used as a
potential proliferative marker to observe the aggressive behaviour of
ameloblastomas and KCOTs.
PMID- 28706783
TI - The anecdote of viral etiopathogenia in ameloblastoma and odontogenic keratocyst:
Why don't we let it go?
AB - BACKGROUND: Ameloblastoma (AM) and odontogenic Keratocyst (OKC) are destructive
odontogenic lesions of the gnathion. Although their exact pathogeneses are not
yet totally understood, the viral etiopathogenesis in AM and KCOT has been
proposed. True to syndromic keratocystic odontogenic tumor (sKCOT) and non
syndromic OKC is the high recurrence rate. OBJECTIVES: Given that shared pathways
trailed by AM and by sKCOT/OKC have been suggested, this study, however,
contrasts the expression of AM and OKC for viral antibodies. METHOD: A total of
archival 80 paraffin blocks of cases of parakeratinized odontogenic keratocyst
(non-syndromic KCOTs) and of ameloblastomas (n = 40 for each) were included in
this study to be sectioned and stained for two immunohistochemical markers: anti
human papillomavirus and Epstein-Barr virus-encoded latent membrane protein.
RESULTS: All the submitted cases of AM and parakeratinized OKC were negative for
both markers: anti-HPV and anti-LMP-1. CONCLUSIONS: Although results could have
been biased, given the same ethnic group and territory examined in this study,
all cases were negative for both markers. Therefore, the viral contribution to
the etiopathogenesis in AM and OKC could not be established in this study.
PMID- 28706784
TI - Healing of extraction socket following local application of simvastatin: A split
mouth prospective study.
AB - BACKGROUND: The role of simvastatin in lowering serum cholesterol level is well
described. However, recent findings suggest they have a role in bone formation as
well. AIM AND OBJECTIVES: The present prospective study was conducted to evaluate
the efficacy of simvastatin on bone formation in extraction sockets. MATERIALS
AND METHODS: 15 patients undergoing all four first premolar extraction were
selected based on inclusion and exclusion criteria. Extraction sockets of left
premolars (24 and 34) were considered as cases and right premolars (14 and 44) as
controls. Overall 30 extraction sites were assigned to each group. Atraumatic
extraction was done in all cases following which simvastatin mixed with gelatin
sponge was placed in extraction socket of 24 and 34 while only gelatin sponge was
placed in 14 and 44. All sockets were then closed with 3-0 vicryl. The patients
were kept on follow-up and complications such as dry socket, pain, and swelling
were recorded. Intra oral peri apical radiographs were taken immediately after
extraction and at 2nd month and 4th month to record changes in the density of
alveolar bone. The radiographic measurements were compared and the differences
were statistically analyzed. RESULT: Percent increase in bone density at the end
of 8th week and 16th week was significantly high in case as compared to the
control group. CONCLUSION: Local application of simvastatin induces bone
formation in extraction sockets. Application is very simple and provides a very
cost effective way of faster bone regeneration following tooth extraction.
PMID- 28706785
TI - Effect of in-situ application of simvastatin gel in surgical management of
osseous defects in chronic periodontitis-A randomized clinical trial.
AB - BACKGROUND: The present randomized controlled clinical study was designed to
investigate the effect of in situ application of 1.2 mg Simvastatin (SV) gel in
the surgical management of Intrabony defects in chronic periodontitis patients.
METHODOLOGY: 20 patients contributing 40 sites were categorized into two
treatment groups: Open flap debridement plus 1.2 mg SV gel (Group 1) and Open
flap debridement plus Placebo gel (Group 2). Gingival index (GI), Plaque index
(PI), Pocket depth (PD) and clinical attachment level (CAL) were recorded at
baseline, 3 months, 6 months and 9 months. At baseline and at the end of 6 and 9
months Radiographic evaluation of Intrabony defect fill was done using Image j
software. RESULTS: Significant reduction of GI, PD and gain in CAL was observed
at the end of 9 months in both groups. Amount of bone fill and percentage of
original defect fill in Group 1 was statistically highly significant than Group 2
at the end of 6 and 9 months. CONCLUSION: Higher amount of decrease in GI and PD
along with more amount of CAL gain was observed in treatment group than control
group. Radiological assessment confirmed that significant intrabony defect fill
and percentage fill of original defect in treatment group than controlled group.
PMID- 28706786
TI - Role of 1.5 mm microplates in treatment of symphyseal fracture of mandible: A
stress analysis based comparative study.
AB - AIMS AND OBJECTIVES: To perform comparative finite element analysis (FEA)for 2.0
mm standard miniplate and 1.5 mm microplate in isolated symphyseal mandibular
fractures. MATERIAL AND METHOD: Two FE models of mandible were developed and
symphyseal fracture was created in both of them. Each fractured model was reduced
and fixed using two mini plates and two microplates, respectively according
Champ's principle. Stresses thus developed in the plates after application of
masticatory load were observed in the models. RESULTS: Results of the study
indicated there was no significant difference in the stresses developed in either
of the bone plating system. CONCLUSION: 1.5 mm Microplates can be used in place
of 2.0 mm miniplates in isolated symphyseal fractures of the mandible.
PMID- 28706787
TI - Effect of scaling & root planing on the activity of ALP in GCF & serum of
patients with gingivitis, chronic and aggressive periodontitis: A comparative
study.
AB - INTRODUCTION: Host response and environmental factors are known to modify
periodontal status adversely. Presently serum, saliva, and GCF are being
investigated for its biochemical constituents. GCF contains array of biochemical
factors, offering potential use as a diagnostic or prognostic biomarker of the
biologic state of the periodontium in health and disease. Alkaline phosphatase is
produced locally in the periodontium and shows positive correlation with disease
activity and PD. Present study was designed to analyze the levels of ALP in GCF
and serum of patients with gingivitis, chronic & aggressive periodontitis before
and after SRP & to compare the difference within the study groups. METHODS: OPD
patients grouped into: Gingivitis, Aggressive periodontitis & chronic
periodontitis patients. Clinical parameters recorded for each patient prior to
therapy. Pooled GCF samples collected using micro capillary tubes from the
deepest pocket sites for each patient and stored at -70 degrees C. Serum samples
also collected and stored at -20 degrees C. Each patient was subjected to
scaling and root planing with two weeks maintenance recall. After 6 to 8 weeks
GCF and serum samples collected again and all clinical parameters rerecorded. GCF
and serum samples analyzed for levels of ALP by using para nitro phenol assay for
the three groups. RESULTS: ALP levels in GCF increased significantly during
active phase of disease followed by statistically significant reduction after
phase I therapy. Baseline levels of ALP in GCF was CP > AP > G with maximum
reduction in GCF ALP after SRP in G > CP > AP group.
PMID- 28706788
TI - Post-traumatic superolateral dislocation of condyle: A case series of 18 condyles
with review of literature and a proposed classification.
AB - AIM: The aim is to review the English literature for post-traumatic superolateral
dislocation of mandibular condyle (SDMC),discuss their dynamics and clinical
management and to propose to modify the existing classification of SDMC. PATIENTS
AND METHODS: A literature search was carried at Pubmed, Sciencedirect, Google and
references from reported articles were crosschecked to look for the cases of SDMC
from 1969 to 2015 in English language. Also, we have reviewed 11 of our patients
with total of 18 superolateral dislocated intact or sagittal split condyles ,who
visited our unit in the previous two years. RESULTS: In our retrospective
analysis 58 cases of SDMC were found in the literature, of which 38 had intact
mandibular condyles and 20 had sagittal split. Early and intact SDMC were
successfully managed conservatively with closed reduction, whereas old cases and
largely fractured condyles necessitated open reduction. Additionally, we observed
an unusual dislocation associated with fracture of contralateral posterior
mandible(angle) in our series which did not gratify the existing classification.
CONCLUSION: Alteration of the existing classification was required to accommodate
the unusual type of dislocation.
PMID- 28706789
TI - Craniometaphyseal Dysplasia: A review and novel oral manifestation.
AB - Craniometaphyseal Dysplasia (CMD) is a sclerosing osseous dysplasia characterised
by hyperostosis of craniofacial and long bones, resulting in distortion and
cranial nerve palsies. We present a case report on the management of a 63 year
old female with Craniometaphyseal Dysplasia. This report describes an additional
clinical manifestation of hypercementosis, which although well recognised in
other sclerosing osseous dysplasias, is not reported in the literature for
Craniometaphyseal Dysplasia. We discuss established in vivo studies in mice which
link the genetic mutations found in Craniometaphyseal Dysplasia to
hypercementosis, and how this report describes the same manifestation in humans.
This novel finding can aid the clinician in the management of patients with
Craniometaphyseal Dysplasia, and complications that can arise in dentoalveolar
surgery.
PMID- 28706790
TI - A rare case of three single rooted permanent second molars: A diagnosis with cone
beam computed tomography (CBCT).
AB - The aim of this article is to present a case with an unusual morphology of
maxillary second molars on both sides and a mandibular second molar on right side
in the same patient which was observed during routine endodontic procedure. Three
second permanent molars had single root, single canal and an accurate assessment
of this unusual morphology was made with the help of radiographs and cone beam
computed tomography (CBCT). This report extends the range of known possible
anatomical variations to include teeth with lesser number of roots and canals.
PMID- 28706791
TI - A novel approach for restoration of hemisected mandibular first molar with
immediately loaded single piece BCS implant: A case report.
AB - Mandibular first molars are the major standpoint for occlusion, and also have a
wide peri-cemental area. Under specific conditions, hemisection of the tooth is
indicated after an endodontic treatment. The following case report presents the
hemisection of grossly carious, endodontically treated mandibular first molar, in
a 23 year old female, followed by replacement of the mesial root with a single
piece immediate loaded BCS (Bi-Cortical Screw) implant and a single unit
porcelain fused to metal crown for the prosthetic rehabilitation of the remaining
tooth structure, with the BCS implant providing strength and support to the
weakened tooth structure. This procedure is an innovation in prosthetic
rehabilitation of tooth structure left after hemisection and enhances the
predictability of success rate of hemisection.
PMID- 28706792
TI - Simultaneous maxillomandibular distraction osteogenesis in hemifacial microsomia:
Report of 7 cases.
AB - INTRODUCTION: The goal in treating Hemifacial microsomia (HFM) is to improve
facial symmetry, allow functional jaw movement, obtain stable occlusion, and
achieve patient satisfaction. This study was planned with an aim to assess the
outcome of simultaneous maxillomandibular distraction osteogenesis in hemifacial
microsomia. MATERIAL & METHODS: Seven patients with hemifacial microsomia were
included in this study and demographic data was obtained. Simultaneous maxillo
mandibular distraction was planned for correction of maxillary cant, vertical
ramal lengthening and midline, by performing unilateral mandibular osteotomy in
ramus and distractor fixation, a Le Fort I osteotomy, with fixation at
contralateral zygomatic buttress and intermaxillary elastics. Derriford
Appearance Scale was used to measure individual responses to address problems of
appearance. RESULTS: 6 males and 1 female, with age range 18-26 years, mean 22.14
were included in the study. Maxillary occlusal cant varied from 4-16 degrees ,
mean 9.85 degrees and distraction achieved ranged from 12-19 mm, mean 15.57.
Preoperatively DAS score ranged from 42-61, mean 51.7 and improved to 10-27, mean
18.4. 100% success was achieved in 5 cases, while other two showed 96% and 99%
success. CONCLUSION: Simultaneous maxillomandibular distraction osteogenesis
improves facial esthetics and obviates the need for postoperative orthodontics,
minimizing the treatment period.
PMID- 28706793
TI - Medial Meniscus Posterior Root Repair Using a Transtibial Technique.
AB - The meniscal roots are critical in maintaining the normal shock absorbing
function of the meniscus. If a meniscal root tear is left untreated, meniscal
extrusion can occur rendering the meniscus nonfunctional resulting in
degenerative arthritis. Two main repair techniques are described: (1) suture
anchors (direct fixation) and (2) sutures pulled through a tibial tunnel
(indirect fixation). Meniscal root repair using a suture anchor technique is
technically challenging requiring a posterior portal and a curved suture passing
device that can be difficult to manipulate within the knee. We present a
technique for posterior medial meniscus root repair using 3 sutures (1 leader, 2
cinch), standard arthroscopy portals, and transtibial fixation. Overall, this
technique simplifies a challenging procedure and allows for familiarity and
efficiency.
PMID- 28706794
TI - Notchplasty for the Arthroscopic Treatment of Limited Knee Extension.
AB - Knee osteoarthritis may lead to narrowing of the intercondylar notch due to
osteophyte formation, thereby causing changes in native knee biomechanics. The
normal close contact between the condyles and the anterior cruciate ligament
(ACL) during knee extension may be compromised due to narrowing of the notch and
result in ACL damage, progression of knee osteoarthritis, and loss of knee
extension. Outcomes after a notchplasty procedure are well reported for ACL
reconstruction in young patients. However, there remains a lack of studies
evaluating this procedure in the setting of knee osteoarthritis in patients with
a symptomatic loss of knee extension. The purpose of this Technical Note is to
present our preferred surgical technique for the treatment of loss of knee
extension in the setting of knee osteoarthritis in conjunction with osteophyte
formation in the intercondylar notch.
PMID- 28706795
TI - Measurement of Hip Contact Pressure During Arthroscopic Femoroacetabular
Impingement Surgery.
AB - Cam impingement is caused by jamming of an abnormal femoral head with an
increased radius into the acetabulum during motion. Therefore, the elevation of
the contact pressure during the motion is suspected to be an essential pathology
of femoroacetabular impingement. However, there is no method to quantify the hip
contact pressure during motion. The purpose of this Technical Note is to
introduce a technique to measure the hip contact pressure during arthroscopic
surgery. The author believes that the current technique will be a useful tool for
the detailed investigation of the pathophysiology femoroacetabular impingement
and thorough evaluation of its therapeutic significance.
PMID- 28706796
TI - Arthroscopic Removal of a Loose Polyethylene Glenoid Component With Bone Grafting
and Patch Augmentation for Glenoid Osseous Defect.
AB - Glenoid component loosening is a common cause of failed total shoulder
arthroplasty. Many different treatment options exist for the management of a
symptomatic loose polyethylene glenoid component, ranging from component removal
to revision arthroplasty. Arthroscopic removal and conversion to hemiarthroplasty
provides a minimally invasive management option that avoids takedown of the
subscapularis and allows for humeral prosthesis retention. Frequently, however,
osteolysis is encountered concomitantly leading to cavitary glenoid bone deficits
at the time of glenoid implant removal, limiting both immediate and future
treatment options. The purpose of this Technical Note is to describe in detail an
all-arthroscopic technique for removal of a loose polyethylene glenoid component
with subsequent bone grafting of a contained glenoid bone defect, and insertion
of a human dermal allograft patch.
PMID- 28706797
TI - Single Portal Subscapular Repair by a Cross Shuttle Loop Technique.
AB - With the rise in subscapular tendon tears, most of them being partial that
eventually end up in complete tears, we present our experience in the management
of such tears using a cross shuttle loop technique. This technique incorporates
the advantages of a single portal for anchor placement and repair, easy to use
cross loops in limited working space, and familiar viewing.
PMID- 28706798
TI - Arthroscopic Excision of Osteoid Osteoma of the Elbow.
AB - Osteoid osteoma has been reported infrequently around the elbow joint, and is
usually treated with radiofrequency ablation or open excision. Elbow arthroscopy
is useful for excision of accessible lesions, and the accompanying elbow
stiffness can be treated concurrently. This report describes an arthroscopic
excision of an osteoid osteoma located in the juxta-articular distal humeral
bone. An initial adhesiolysis and capsulectomy is performed to gain access to the
region above the capitellar articular margin. A 70 degrees arthroscope is
necessary to visualize this region via the anteromedial portal. An accessory
lateral portal is used to detach the capsule from the distal humerus; the scar
tissue overlying the lesion is debrided and the circumferential lesion is
visualized and probed for identification of its extent. A biopsy is performed,
and thereafter the lesion is excised piecemeal. The sclerotic margins are
curetted, and radiofrequency ablation is performed. The technique is cosmetic and
minimally invasive, and can be performed in revision scenarios involving
recurrences after open surgery or needle radiofrequency thermal ablation. Early
rehabilitation restores range of motion and strength. Technical tips for
identification and curettage of the lesion are presented.
PMID- 28706799
TI - All Arthroscopic Remnant-Preserving Technique to Reconstruct the Lateral Ankle
Ligament Complex.
AB - Arthroscopic lateral ankle ligament reconstruction has been recently advocated.
But this technique has not been popularized because of the technical complexity
and potential iatrogenic injury. Because the talocalcaneal and calcaneofibular
ligaments are extra-articular structures, how to efficiently view and address
them is a difficult task. Limited dissection outside the capsule to form a
working space is required, but aggressive dissection is harmful for tissue
healing although it is helpful for visualization and instrumentation. Because
almost the entire talar body is covered by articular cartilage, it is very
difficult to safely make a bone tunnel without damaging the cartilage. The
remnants of the lateral ankle ligament have proprioceptive sensors that are
important for functional stability, but it is difficult to perform anatomical
reconstruction arthroscopically while preserving them because of the narrow
working space. Furthermore, how to properly tension the reconstructed ligaments
in such a narrow working space is also a very difficult task. We have designed a
technique that preserves the remnants of lateral ankle ligaments, and all of the
above-mentioned problems have been successfully addressed. We have used this
technique clinically, and only minor complications occurred.
PMID- 28706800
TI - Arthroscopic Screw Removal After Arthroscopic Latarjet Procedure.
AB - Arthroscopic Latarjet procedure is an efficient and reliable approach for the
treatment of shoulder instability. Nevertheless, the screws fixing the bone block
may sometimes be responsible for pain and uncomfortable snapping in the shoulder
that is triggered during active external rotation. We propose an all-arthroscopic
technique for screw removal in cases of complications involving the screws from a
Latarjet procedure. The all-arthroscopic screw removal is reliable and efficient.
This procedure is indicated in more cases than thought because of the bone block
resorption. It permits a revision of the glenohumeral joint in case of persisting
pain.
PMID- 28706801
TI - Combined Anatomic Reconstruction of the Anterior Cruciate and Anterolateral
Ligaments Using Hamstring Graft Through a Single Femoral Tunnel and With a Single
Femoral Fixation.
AB - Patients with complete anterior cruciate ligament (ACL) injury have different
degrees of rotational (internal rotation) laxity. A residual pivot shift has been
found to be positive in more than 15% of cases after an accurate ACL
reconstruction. Improved understanding of the existence, function, and
biomechanical role of the anterolateral ligament (ALL) in controlling rotational
instability of the knee has redirected and refocused attention on a supplemental
extra-articular reconstruction of the ALL in conjunction with the intra-articular
ACL reconstruction so as to restore normal kinematics of the knee. This Technical
Note describes a technique that allows for a combined ACL and ALL reconstruction
using autogenous hamstring graft (semitendinosus and gracilis tendons). One
femoral tunnel is used connecting the anatomic femoral attachment of the ALL on
the lateral wall of the lateral femoral condyle to the anatomic femoral ACL
footprint on the medial wall of the lateral femoral condyle. The remaining part
of the graft is fixed to the proximal tibia midway between Gordy's tubercle and
the head of the fibula. This Technical Note describes a technique of both ACL and
ALL reconstruction with a continuous hamstring graft.
PMID- 28706802
TI - Medial Meniscus Posterior Root Tear Repair Using a 2-Simple-Suture Pullout
Technique.
AB - Medial meniscus posterior root tear is one of the underestimated knee injuries in
terms of incidence. Despite its grave sequelae, using simple but effective
technique can maintain the native knee joint longevity. In the current note, a 2
simple-suture pullout technique was used to effectively reduce the meniscus
posterior root to its anatomic position. The success of the technique depended on
proper tool selection as well as tibial tunnel direction that allowed easier root
suturing and better suture tensioning, without inducing any iatrogenic articular
cartilage injury or meniscal tissue loss. Using anterior knee arthroscopy
portals, anterolateral as a viewing portal and anteromedial as a working portal,
a 7-mm tibial tunnel starting at Gerdy tubercle and ending at the medial meniscus
posterior root bed was created. The 2 simple sutures were retrieved through the
tunnel and tensioned and secured over a 12-mm-diameter washer at the tibial
tunnel outer orifice. Anatomic reduction of the medial meniscus posterior root
tear was confirmed arthroscopically intraoperatively and radiologically by
postoperative magnetic resonance imaging.
PMID- 28706803
TI - Arthroscopic Anterior Cruciate Ligament Femoral Tunnel Visualization for Button
Fixation.
AB - Arthroscopic reconstruction of the anterior cruciate ligament (ACL) remains one
of the most commonly performed procedures in orthopaedic surgery. We describe a
technique to visualize the button being advanced through the femoral tunnel using
an arthroscope placed in the anteromedial portal. Looking into the femoral tunnel
in line with the sutures, this technique allows the surgeon to directly visualize
the femoral button as it traverses the femoral tunnel and confirms that it is
engaged over the femoral cortex. Certain complications can arise, however, with
the use of a suspensory fixation with a button on the femoral cortex. This method
can decrease operative time and complication rates.
PMID- 28706804
TI - Tibial Tuberosity Transfer in Combination With Medial Patellofemoral Ligament
Reconstruction: Surgical Technique.
AB - The stability of the patellofemoral joint relies on the tenuous interplay of soft
tissue and bony factors. Anatomic risk factors for instability include a shallow
trochlea, an abnormally lateral tibial tubercle position, patella alta,
hypermobility, or a secondary injury to the medial patellofemoral ligament
(MPFL). There is an increasing interest in restoring normal anatomy to achieve
stability, and at times more than 1 abnormality exists. This article describes
the technique for combining a tibial tuberosity transfer and an MPFL
reconstruction. The key features include planning of skin incisions to enable
both operations to be undertaken, planning of the screw placement before
osteotomy is performed and assessment of the joint through a superolateral portal
to assess the need for MPFL reconstruction after tuberosity transfer.
PMID- 28706805
TI - Arthroscopic Intra-articular Disk Excision of the Sternoclavicular Joint.
AB - The sternoclavicular joint (SCJ) has a complete intra-articular disk that can be
damaged either as a result of trauma or as part of ongoing degenerative joint
disease. Although often asymptomatic, SCJ disk tears may lead to mechanical
symptoms and pain. Previously, isolated symptomatic SCJ disk tears have only
occasionally been mentioned in the literature with a few associated case reports
of diskectomy by open arthrotomy. With improved imaging and availability of
magnetic resonance imaging scans and the advent of SCJ arthroscopy it is now
possible to treat symptomatic SCJ disk tears by arthroscopic excision. In this
Technical Note, we describe the diagnosis of a torn SCJ disk and the technique of
arthroscopic excision of a torn SCJ disk.
PMID- 28706806
TI - Osseoscopy: Direct Visualization to Assist Core Decompression and Debridement of
Necrotic Bone Defects.
AB - Free vascularized fibular grafting after core decompression and debridement of
necrotic lesions is an effective surgical treatment of avascular necrosis of the
femoral head. A technical challenge encountered in performing this procedure is
ensuring adequate debridement of necrotic parts while preserving healthy bone. A
previously described method accomplishes this indirectly using radioactive
contrast media and fluoroscopy, increasing the risk of radiation exposure. We
propose a surgical technique using standard arthroscopic equipment to visualize
inside the femoral head, facilitating precise and accurate debridement without
additional radiation exposure.
PMID- 28706807
TI - Labral Gracilis Tendon Allograft Reconstruction and Cartilage Regeneration
Scaffold for an Uncontained Acetabular Cartilage Defect of the Hip.
AB - Hip cartilage injuries are very common, with rates as high as 50% having been
reported in some series; abnormal femoral acetabular contact can result in a full
thickness cartilage defect or labral lesion. The prevalence of labral lesions can
be as high as 55%. This Technical Note describes an arthroscopic technique to
reconstruct an uncontained, full-thickness, focal cartilage defect of the
acetabulum, with reconstruction of the missing labrum using a gracilis allograft
and use of a biological liquid scaffold for cartilage reconstruction.
Capsulotomy, acetabuloplasty, and microfracture with marrow bleeding should be
performed simultaneously with the gracilis allograft preparation. The graft is
inserted and anchored to reconstruct the missing labrum and to re-create a
contained defect. Suction and drying of the joint surfaces are performed while
the mixture of BST-CarGel (Piramal Healthcare, Laval, Quebec, Canada) and blood
is prepared. A drop-by-drop technique is then used to reconstruct the cartilage
defect.
PMID- 28706808
TI - Transosseous Posterior Meniscal Root Reinsertion Using Knotless Anchor for Tibial
Fixation.
AB - A technique for posterior meniscal root reinsertion is presented. With the
arthroscope in the central transtendinous portal for a better view, a 5-mm
transtibial tunnel is created with the aid of an anterior cruciate ligament guide
open to 45 degrees . A suture device, which consists of a long needle with an
eyelet on its tip, is introduced through the tunnel with a suture thread inserted
through the eyelet, while the meniscus is stabilized with a grasper inserted
through the anterior portal. The meniscus is pierced with the device, and the
suture thread is recovered with said grasper. A finger-tip pincer is inserted
through the tunnel to recover the thread. The same procedure is followed to
perform a second stitch. A lasso loop is made for both stitches, and the
resultant tails are knotted to a knotless suture anchor, which is inserted in the
anterior cortex of the tibia, 1 cm distal to the extra-articular end of the
tibial tunnel.
PMID- 28706809
TI - Posterolateral Acetabuloplasty and Distal Femoral Neckplasty, Labral Repair, and
Capsular Plication for Hip Reverse Contre-Coupe Lesion.
AB - This article describes the arthroscopic approach and management of a "reverse
contre-coup" injury to the hip labrum. The injury occurs in the setting of
posterolateral acetabular rim over-coverage impinging on the distal femoral neck
in extension causing the femoral head to lever out anteriorly against the labrum.
Ligamentous laxity and associated loss of anterior capsular restraint allow
increased femoral head translation, adding further insult to the anterior labrum.
The arthroscopic approach entails not only a labral repair with correction of the
osseous conflict but also restoration of soft-tissue stability to minimize
anterior femoral translation.
PMID- 28706810
TI - A Simple, All-Arthroscopic, Knotless Suture Lasso Loop Technique for
Suprapectoral Biceps Tenodesis.
AB - A variety of pathology of the long head of the biceps tendon can contribute to
anterior shoulder pain in adults that can be managed with either arthroscopic
tenotomy or tenodesis when conservative treatment fails. Biceps deformity or the
Popeye sign is a major concern in patients after tenotomy. Biceps tenodesis can
be performed in a variety of ways with different sized anchors and at different
locations (suprapectoral or subpectoral). Several studies have shown that patient
outcomes and complication rates are similar between all-arthroscopic
suprapectoral biceps tenodesis and open subpectoral biceps tenodesis. We describe
a simple, knotless, arthroscopic intra-articular biceps tenodesis technique using
a 1.5-mm LabralTape lasso loop technique and a 2.9-mm PushLock anchor.
PMID- 28706811
TI - Surgical Technique for Arthroscopy-Assisted Anatomical Reconstruction of
Acromioclavicular and Coracoclavicular Ligaments Using Autologous Hamstring Graft
in Chronic Acromioclavicular Joint Dislocations.
AB - Injuries to the acromioclavicular (AC) joint are becoming common with contact
sports and bike accidents. It is well known that in AC dislocations, the first
structure to fail is the AC capsule followed by the trapezoid and conoid
ligaments. The function of these ligaments must be restored to restore the
anatomy and physiology of the AC joint to get the best results. Until now, no
technique has emerged as the gold standard for restoration of the AC joint
anatomy and function. In our technique, the stress is on recreating the anatomy
to make it more individualized based on individual variations. This Technical
Note describes a procedure to reconstruct the coracoclavicular ligaments and AC
joint by an arthroscopy-assisted technique. Arthroscopy helps to diagnose
additional intra-articular pathologies that can be treated simultaneously, and
better preparation of the undersurface of the coracoid helps in bone-to-graft
healing. Our approach is more individualized as clavicle tunneling is done
according to the size of the coracoid base instead of a fixed distance. Vertical
stability is provided by coracoclavicular ligament reconstruction, horizontal
stability is provided by AC ligament reconstruction, and the articular disc is
recreated by soft-tissue graft interposition, thus restoring the complete
anatomy.
PMID- 28706812
TI - Mini-Open Posterior Compartment Release for Chronic Exertional Compartment
Syndrome of the Leg.
AB - Chronic exertional compartment syndrome (CECS) is a well-recognized cause of leg
pain in endurance athletes. Surgical fasciotomy for posterior leg CECS
historically has inferior clinical results compared with anterior and lateral
compartment release. Poor surgical technique with inadequate release may
contribute to less reliable outcomes. In this Technical Note with accompanying
video, we describe a mini-open approach for posterior CECS of the leg.
PMID- 28706813
TI - All-Inside Bicruciate Ligament Reconstruction Technique: A Focus on Graft
Tensioning Sequence.
AB - Bicruciate ligament (BCL) reconstructions are challenging procedures. One of the
main operative goals is to stabilize the knee in the correct anterior-posterior
position. We present an all-inside arthroscopic BCL reconstruction technique
using hamstring tendon grafts. Ipsilateral semitendinosus (ST) and gracilis
tendons are used for TriLink (Arthrex, Naples, FL) double-bundle posterior
cruciate ligament (PCL) reconstruction and contralateral ST tendon is used for
GraftLink (Arthrex) single-bundle anterior cruciate ligament (ACL)
reconstruction. The use of instruments for retrograde reaming and devices for
adjustable cortical suspensory fixation allows for a safe, reproducible all
inside BCL reconstruction by simplifying these difficult steps. To minimize the
risk of anterior-posterior malposition, the ACL graft is first tensioned with the
knee in full extension, ensuring a neutral anteroposterior positioning of the
tibia under the femur. The PCL anterolateral bundle can then be independently
tensioned with the knee at 90 degrees of flexion, and the posteromedial bundle
at 30 degrees of flexion, while applying an anterior translation to the tibia to
reduce the posterior drawer without any risk of overcorrection. The purpose of
this Technical Note was to describe an all-inside BCL reconstruction with a
specific focus on the graft tensioning sequence.
PMID- 28706814
TI - Tibial Allograft Transfer for Medial Tibial Plateau Resurfacing.
AB - A large cartilage lesion of the tibial plateau with a deficient meniscus in a
young patient is a challenging pathology for the orthopaedic surgeon due to the
limited options available. While hemiarthroplasty procedures can be an option,
the risk of revision in a young patient is high, and therefore a reconstructive
procedure is advocated. The purpose of this Technical Note is to describe our
technique for tibial plateau resurfacing, including the preparation and
implantation of a medial tibial plateau and medial meniscal allograft, in a
patient with a post-traumatic KD-4 knee dislocation with a medial tibial plateau
rim fracture, medial meniscus deficiency, and medial tibiofemoral joint
subluxation.
PMID- 28706815
TI - Arthroscopic Subcapital Realignment in Chronic and Stable Slipped Capital Femoral
Epiphysis.
AB - Stable slipped capital femoral epiphysis (SCFE) is the most common disease in the
adolescent hip, with an estimated frequency of 10.8 in every 100,000 individuals.
Recent studies of the biomechanics of femoroacetabular impingement indicate that
small anatomical deformities of the hip arising from SCFE can potentially cause
permanent acetabular chondral damage. There is no consensus about the best
treatment option, especially for cases of moderate or severe chronic slippage
(Southwick classification). Some authors recommend treatment with fixation in
situ, in the belief that remodeling of the residual deformity of the femoral neck
during growth allows proper function of the hip joint. Others recommend
correction at the site of the deformity (subcapital realignment), aiming for the
anatomical reduction of the epiphysis and seeking to reduce the risk of chondral
degeneration. The authors of this Technical Note present an alternative to the
classical techniques of subcapital realignment for the treatment of moderate and
severe chronic and stable SCFE, which allows adequate access to the hip joint and
anatomical reduction of the slippage, besides having the theoretical advantage of
rapid rehabilitation of the patient.
PMID- 28706816
TI - Endoscopic Stalk Resection of a Toe Ganglion With Color-aided Visualization.
AB - Ganglion cysts are common cystic lesions filled with a jelly-like substance and
originate from a joint capsule or tendon sheath through a stalk. Ganglion cysts
mostly occur in the hand region, for which surgical excision usually results in
good outcomes. In contrast, toe ganglions are relatively rare, and surgical
treatment is associated with a high recurrence rate because of unidentifiable
ganglion stalks, requiring large skin incisions. We have treated toe ganglion
cysts using endoscopy in the ganglion cyst by injecting methylene blue into the
tendon sheath that connects to the ganglion stalk. The result has been favorable,
without recurrence. The advantages of our technique include the following: (1)
Endoscopy using a color aid can show the location of a ganglion stalk, and
removing the stalk can prevent recurrence. (2) Endoscopic stalk-only resection is
minimally invasive, allowing early mobilization and reducing surgical-site
complications. The purpose of this Technical Note is to describe our endoscopic
stalk resection technique with color-aided visualization, and we have included a
video presentation.
PMID- 28706817
TI - The "Pull-Over" Technique for All Arthroscopic Rotator Cuff Repair With
Extracellular Matrix Augmentation.
AB - Despite the vast improvement in techniques for arthroscopic rotator cuff surgery,
repairs of massive and large tears remain an issue as they are associated with
significantly high failure rates, particularly in the elderly population. As a
result, there has been a focus of attention to improve rotator cuff repair
healing rates. One of the strategies is augmentation of the repair with a patch.
Arthroscopic augmentation is, however, technically demanding with challenges in
introduction and stabilization of the patch. The purpose of this Technical Note
is to describe a technique for arthroscopic rotator cuff repair with
augmentation, which offers additional advantages over previous techniques because
it facilitates the passage of the patch as well as providing a more robust medial
stabilization of the augment and therefore possibly a stronger construct.
PMID- 28706818
TI - Arthroscopic Repair of Posterior Bony Bankart Lesion and Subscapularis
Remplissage.
AB - Posterior shoulder instability with glenoid bone loss has only a fraction of the
prevalence of anterior instability. Unlike the latter, there is a paucity of
literature regarding the treatment of posterior bony Bankart lesions and even
less with concomitant reverse Hill-Sachs lesions. This combination of pathology
leads to a difficult situation regarding treatment options. We present our
technique for arthroscopic repair of a posterior bony Bankart lesion and reverse
Hill-Sachs lesion. The importance of proper portal placement cannot be
overstated. By use of the lateral position and strategically placed portals, the
posterior bony Bankart lesion and attached labral complex were appropriately
mobilized. We reduced the glenoid bone, with the attached capsulolabral complex,
to the glenoid rim and performed fixation using a knotless suture anchor. We then
placed 2 double-loaded suture anchors into the reverse Hill-Sachs lesion. The
sutures were passed creating horizontal mattress configurations that were tied at
the end of the procedure, effectively externalizing the humeral head defect. Our
technique results in satisfactory fragment reduction, as well as appropriate
capsular tension, and effectively prevents the reverse Hill-Sachs lesion from
engaging.
PMID- 28706819
TI - Circumferential Labral Reconstruction Using the Knotless Pull-Through Technique
Surgical Technique.
AB - Arthroscopic labral reconstruction is an alternative procedure for an irreparable
hip labrum in the nonarthritic hip population. Although labral reconstruction is
a relatively new procedure, data in the literature show favorable outcomes.
Patients have shown beneficial outcomes from labral reconstructive surgery as
well as when compared with labral repair and debridement patients. However, one
of the challenges in performing labral reconstruction has been correctly
measuring the graft to perfectly fit the area of labral deficiency. We propose a
labral reconstruction technique that will eliminate inaccuracies in graft
measurement while incorporating beneficial characteristics of the knotless
suture. The advantages of this technique will increase procedural accuracy and
brevity.
PMID- 28706820
TI - Basic Hip Arthroscopy: Diagnostic Hip Arthroscopy.
AB - Hip arthroscopy is increasing in popularity for the diagnosis and management of
hip preservation. The basics of hip arthroscopy positioning, fluoroscopic
assessment, and portal establishment are reviewed in the first 2 parts of this
series. This article is the third installment in which we describe a systematic
approach to performing a diagnostic hip arthroscopy. A mastery of diagnostic
arthroscopy is necessary for surgeons treating hip disorders.
PMID- 28706821
TI - Arthroscopic Transtendinous Biceps Tenodesis With All-Suture Anchor.
AB - There are several methods for long head of the biceps (LHB) tenodesis, yet the
optimal option is still debatable. Here we introduce a technique for arthroscopic
suprapectoral biceps tenodesis with an all-suture anchor, the transtendinous
biceps tenodesis technique. The LHB tenodesis is performed by using the Y-Knot
anchor (1.3-mm). A standard suprapectoral approach is used for the tenodesis. A
1.3-mm drill bit is used to drill through the midportion of the biceps tendon and
underlying bone to make a pilot hole. Next, the Y-Knot anchor is passed through
the tendon and anchored on the underlying bone. A wrapping suture technique is
then used to wrap around, tension, and secure the LHB tendon with the aid of a
shuttling polydioxanone suture. The construct is fixed by tying down both suture
limbs in a nonsliding fashion. This Technical Note describes an alternative
method for all-arthroscopic suprapectoral biceps tenodesis using an all-suture
anchor with a small diameter to minimize trauma to the tendon.
PMID- 28706822
TI - Endoscopic Fasciotomy of the Superficial and Deep Posterior Compartments of the
Leg.
AB - Chronic exertional compartment syndrome is a rare cause of lower leg pain
incurred during sports activities and typically affects young athletes who need
to return to their activity level as quickly as possible. Nonoperative treatments
are often unsuccessful and fasciotomy of the involved compartment is the
treatment of choice. Endoscopically assisted release of the anterior and deep
compartments is proven to be safe and effective. Endoscopically assisted deep
posterior compartment release via an incision 1 to 3 cm behind the medial tibial
border has high risk of injury to the great saphenous and perforating veins and
the saphenous nerve. The purpose of this Technical Note is to describe the
details of endoscopic fasciotomy of the superficial and deep posterior
compartments of the leg. The operative field of this approach is away from the
saphenous vein and nerve. Moreover, the tibial insertion of the soleus muscle
does not need to be released to gain access to the proximal part of the deep
posterior compartment.
PMID- 28706823
TI - Joint Preservation Surgery for Medial Compartment Osteoarthritis.
AB - Single compartment osteoarthritis is a commonly encountered condition in the
middle-aged population, with the medial compartment being the most commonly
involved compartment. Medial compartment osteoarthritis becomes seriously
disabling for these active patients, with a very few definitive solutions. These
patients quickly stop responding to the conservative methods such as lifestyle
modification, drugs, physiotherapy, and rehab programs. Less invasive procedures
such as intra-articular injections or joint debridement also do not give a long
lasting relief. On the other hand, this population is too young to undergo a knee
replacement surgery because the failure rate of a knee replacement surgery is too
high in the middle-aged patients as compared with the elderly population. A
combination of biological stimulation of the damaged single compartment cartilage
and biomechanical correction surgery can give a long-lasting relief in the middle
aged population. Because the medial compartment osteoarthritis is increasingly
being treated with joint preservation surgeries, it is important to lay out the
step-by-step surgical technique of a joint preservation surgery. This Technical
Note presents the detailed technique, patient selection flow chart, tips, pearls,
and surgical decision making, along with a surgical video of a joint preservation
surgery.
PMID- 28706824
TI - Pectoralis Major Repair With Unicortical Button Fixation And Suture Tape.
AB - Although injuries of the pectoralis major muscle are generally uncommon, ruptures
of the pectoralis major are occasionally seen in younger, more active patients
who participate in weightlifting activities. These injuries usually occur during
maximal contraction of the muscle, while in extension and external rotation. In
the case of a rupture, operative treatment is advocated especially in young,
active patients regardless of the chronicity of the injury. Various surgical
techniques for reattachment of the avulsed tendon have been described, but bone
tunnel and suture anchor repair techniques are most widely used. In this
Technical Note, we present our preferred technique for acute pectoralis major
rupture repair involving use of cortical buttons for tendon stump-to-bone
fixation.
PMID- 28706825
TI - Treatment of Irreducible Traumatic Anterior Shoulder Dislocation Caused by
Subscapularis Tendon Interposition.
AB - Irreducible shoulder dislocation is an uncommon event. When it does occur, blocks
to reduction can include bone, labrum, rotator cuff musculature, or tendon.
Concomitant rotator cuff tear at the time of initial dislocation is not an
exclusive complication of anterior shoulder dislocation in the older population.
Indeed, rotator cuff tear should not be excluded based solely on the patient's
age. Rotator cuff interposition is not an uncommon complication after anterior
dislocation of the shoulder. It should be suspected when there is incongruency of
the joint and persistent subluxation on postreduction radiographs. If such
incongruence or subluxation is seen, a computed tomographic (CT) or magnetic
resonance imaging (MRI) scan must then be obtained to determine the nature of the
interposed soft tissues. The key to treatment is early diagnosis and adequate
imaging. Open reduction and repair of the rotator cuff should be performed. We
present a technique for treating irreducible anterior shoulder dislocation caused
by interposition of the subscapularis tendon. Both CT and MRI observations, along
with intraoperative findings and surgical technique, are discussed.
PMID- 28706826
TI - Arthroscopic Panlabral Repair With Remplissage of Hill-Sachs Lesion.
AB - Recurrent shoulder instability in young contact athletes has been well
established. The importance of bipolar bone loss in instability has come to the
forefront in terms of proper management of this condition. It remains
controversial, however, which patients would be better served with an
arthroscopic versus open procedure and when additional procedures may reduce the
risk of failure (i.e., remplissage). We present our arthroscopic technique of a
panlabral repair with concomitant remplissage using the double-pulley technique.
The purpose of this article is to provide insight into obtaining superior
visualization while reviewing surgical pearls and pitfalls to efficiently perform
a panlabral repair and remplissage.
PMID- 28706827
TI - Surgical Technique for Arthroscopic Resection of Painful Bipartite Patella.
AB - Bipartite patella (BP) is uncommon and is usually an incidental finding. Painful
BP occurs rarely and is usually associated with post-traumatic anterior knee
pain. When nonoperative treatment fails, fragment resection is indicated. A
systematic review shows a potentially increased risk of complications with open
surgery. The purpose of this Technical Note is to demonstrate a simple
arthroscopic technique for treating painful BP through resection of the bone
fragment.
PMID- 28706828
TI - Accurate Positioning of Femoral and Tibial Tunnels in Single Bundle Anterior
Cruciate Ligament Reconstruction Using the Indigenously Made Bernard and Hurtle
Grid on a Transparency Sheet and C-arm.
AB - Many factors determine the outcome of the anterior cruciate ligament
reconstruction surgery. The single most important factor, also well within the
control of a surgeon, is tunnel placement. It is difficult to accurately
determine the center of the anterior cruciate ligament foot print, and many a
times it is also difficult to accurately define the intercondylar and bifurcate
ridge. This makes determination of the accurate entry point of the guidewire
difficult. We have printed our indigenously formed grid (equidistant boxes) on an
old-fashioned transparency sheet. We use a fluoroscopy (C-arm) shot
intraoperatively in the lateral position and superimpose this sheet to determine
the position of the guidewire by calculating the percentage of boxes. We aim at
27.7% in proximal to distal and 37.5% in anterior to posterior on the femur side
and 45% in front to back and medial to lateral on the tibial side. C-arm is
freely available, but the inbuilt grid facility may be available in only the
higher version of C-arms. Our indigenously designed grid can be easily used
across the globe with ease to achieve accuracy in tunnel placement without
violating anatomy and without any extra cost.
PMID- 28706829
TI - Platelet-Rich Plasma Augmentation for Hip Arthroscopy.
AB - Biological augmentation and therapeutics are being increasingly used in
musculoskeletal and orthopaedic care. Platelet-rich plasma (PRP) is produced from
centrifugation of peripheral blood, a process that concentrates platelets within
autologous plasma. The process of PRP preparation is fundamental in controlling
the contents, and it influences its therapeutic potential. Platelets contain
alpha granules that store and release a variety of growth factors and other
proteins that may augment the healing environment; PRP also has the added benefit
of promoting postsurgical hemostasis. The purpose of this report was to detail
our institutional preparation protocol and method of administration of PRP during
hip arthroscopy.
PMID- 28706830
TI - A Single-Tunnel Technique for Coracoclavicular and Acromioclavicular Ligament
Reconstruction.
AB - Acromioclavicular (AC) joint separation is a common injury seen in the young
adult athletic population. Both the indications for surgical management and the
best operative technique remain controversial. One of the most popular
reconstruction techniques is the anatomic double-tunnel coracoclavicular (CC)
ligament reconstruction. However, there have been several case reports of
clavicle fractures with this technique. This article presents a single-tunnel
reconstruction technique that aims to restore both the CC and AC ligament
function, while minimizing fracture risk.
PMID- 28706831
TI - Arthroscopic Treatment of Greater Tuberosity Avulsion Fractures.
AB - Isolated fractures of the greater tuberosity of the humerus are an uncommon and
frequently missed diagnosis. Mistreated and unrecognized, these fractures can
cause chronic pain and diminished shoulder range of motion and function.
Operative treatment options include open reduction and internal fixation, as well
as arthroscopic-assisted reduction and internal fixation. The purpose of this
Technical Note is to describe a bridging arthroscopic technique for the treatment
of bony avulsions of the supraspinatus tendon.
PMID- 28706832
TI - Iliotibial Band Lengthening: An Arthroscopic Surgical Technique.
AB - Iliotibial (IT) band syndrome is a common cause of lateral knee pain in runners
and cyclists. Many can be treated nonoperatively; however, some may require
surgical lengthening of their IT band to achieve optimal pain relief and a return
to preinjury level of activity. Several studies have been published detailing
surgical lengthening procedures and satisfactory outcomes after these procedures.
However, it is important to continue to improve on and optimize outcomes. We
present our arthroscopic IT band-lengthening procedure.
PMID- 28706833
TI - Latarjet Technique for Treatment of Anterior Shoulder Instability With Glenoid
Bone Loss.
AB - Anterior glenohumeral instability is a common clinical entity, particularly among
young athletic patient populations. Nonoperative management and arthroscopic
treatment of glenohumeral instability have been associated with high rates of
recurrence, particularly in the setting of glenohumeral osseous defects. Coracoid
transfer, particularly the Latarjet procedure, has become the treatment of choice
for recurrent anterior glenohumeral instability in the setting of osseous
deficiencies greater than 20% to 30% of the glenoid surface area and may also be
considered for the primary treatment of recurrent instability in the high-risk
contact athlete, even in the setting of limited osseous deficiency. The following
Technical Note provides a diagnostic approach for suspected glenohumeral
instability, as well as a detailed description of the congruent-arc Latarjet
procedure, performed with a deltoid split, with its postoperative management.
PMID- 28706834
TI - Screw Fixation of Os Acetabuli: An Arthroscopic Technique.
AB - An os acetabuli (OA) increases the contact area and surface area of the
acetabulum and is important to maintain congruity of the hip joint. Thus
preservation of this ossicle is important to prevent loss of contact area and
ensure containment of the femoral head. We describe an all-arthroscopic approach
to the fixation of OA with a compression screw. Initially, the fibrous tissue is
debrided between the acetabular rim and the OA, a guidewire is placed through the
OA up to the acetabular rim, and a screw is inserted over the wire. Compression
of the OA is achieved with bone-to-bone contact. This technique prevents loss of
femoral head coverage, reducing the risk of subluxation and subsequent
osteoarthritis.
PMID- 28706835
TI - Surgical Technique for Open Reduction-Internal Fixation of an Unstable Displaced
3-Part Proximal Humeral Fracture Using a Proximal Humeral Locking Plate.
AB - The proximal humeral locking plate (PHLP) is a recently developed fixed-angle
implant that is an option for open reduction-internal fixation of an unstable
displaced proximal humeral fracture. Various articles have reported successful
outcomes using the PHLP when compared with other implant designs. However, many
complications still occur with use of the PHLP, such as avascular necrosis of the
humeral articular fragment, malreduction (particularly varus malalignment), and
screw penetration. These complications are related to the difficulty in fixation
of this particular type of fracture, as well as ineffective surgical technique.
We have therefore proposed a step-by-step surgical technique for open reduction
internal fixation of an unstable displaced 3-part proximal humeral fracture using
a PHLP. This technique focuses on the precise placement of the PHLP according to
the plate design, as well as an effective intraoperative assessment, to improve
surgical outcomes and prevent the various complications of proximal humeral
fractures.
PMID- 28706836
TI - Arthroscopic Treatment of Capitellum Osteochondritis Dissecans With Micronized
Allogeneic Cartilage Scaffold.
AB - Osteochondritis dissecans (OCD) of the capitellum is a common disorder that
causes pain and functional limitation in the adolescent elbow. Although
conservative management is the first line of treatment, surgical intervention is
usually recommended for patients with persistent mechanical symptoms, loose
bodies, or unstable lesions. Elbow arthroscopy has become the gold standard to
evaluate and treat symptomatic OCD lesions. Arthroscopic debridement and bone
marrow stimulation have been shown to yield good short-term results.
Unfortunately, long-term follow-up has shown less favorable outcomes, with
degenerative changes frequently documented. Current marrow stimulation techniques
promote the formation of fibrocartilage, which is known to be less durable than
hyaline cartilage. We describe an arthroscopic technique of debridement and
drilling supplemented with a micronized allogeneic cartilage scaffold to address
OCD lesions of the capitellum in an effort to promote hyaline cartilage
formation.
PMID- 28706837
TI - Intraosseous Infiltration of Platelet-Rich Plasma for Severe Hip Osteoarthritis.
AB - This work describes a technique of platelet-rich plasma (PRP) infiltration for
the treatment of severe hip osteoarthritis (OA). Although the results achieved
with intra-articular infiltrations of PRP are promising, they may be insufficient
in the long-term for severe hip OA. The technique consists of a combined intra
articular and intraosseous infiltration of PRP to reach all joint tissues,
especially the subchondral bone, and hence facilitate a greater distribution of
PRP. Diagnosis is based on clinical and radiographic findings, and patients with
grade III OA according to the Tonnis scale, as well as patients who have not
responded to conventional treatment, are considered candidates for this
technique. After an ultrasound-guided intra-articular PRP infiltration is
performed, 2 intraosseous infiltrations are conducted with a fluoroscope; the
first injection is applied into the acetabulum and the second into the femoral
head. However, this technique presents more difficulty than the conventional
administration, so it is necessary to consider several aspects described in this
work.
PMID- 28706838
TI - Endoscopic Decompression of a Gouty Tophus at the Hand Dorsum.
AB - Medical treatment including lifestyle and dietary modifications and drug therapy
remains the mainstay of treatment for gouty arthritis of the hand and wrist.
Without proper and timely treatment, tophi develop approximately 10 years after
the onset of the disease. Open surgery for tophaceous gout is associated with a
relatively high rate of complications particularly related to the surgical wound
and overlying skin necrosis. Intralesional shaving of the tophi through small
incisions has been reported and has the advantage of fewer wound complications.
However, this is a blind procedure, and the underlying tendons and neurovascular
bundles are at risk. The purpose of this Technical Note is to report an
endoscopic approach to debulking a gouty tophus at the hand dorsum. This allows
the minimally invasive debulking procedure to be performed under endoscopic
visualization and reduces the risk of injury to the tendon and neurovascular
structures.
PMID- 28706839
TI - Suspensory Fixation Device for Use With Bone-Patellar Tendon-Bone Grafts.
AB - Good to excellent results at long-term follow-up have been published for bone
patellar tendon-bone (BTB) graft anterior cruciate ligament reconstruction.
Fixation using screws historically has been the most common choice for femoral
and tibial bone blocks, but screws present several disadvantages, which include
the risk of blowout (for which prevention implies having to shift the position of
the tunnel anteriorly), as well as lesions of the bone blocks and tendons. This
article describes a technique using Pullup BTB adjustable-loop length suspensory
fixation (SBM, Lourdes, France) on the femoral and tibial sides. The graft is
harvested and prepared classically. This device combines the advantages of
suspensory fixation (precise position of the tunnel, high tensile strength), with
the advantages of the adjustable loop (control of bone block position within the
femoral tunnel, possibility of retightening the graft) and allows for double
passage of the loop through each bone block for increased safety. So, it could
represent an interesting and secure option for anatomic reconstruction of the
anterior cruciate ligament when a BTB graft is chosen.
PMID- 28706840
TI - Arthroscopic Excision of Osteoid Osteoma of the Talus.
AB - Osteoid osteoma is a benign tumor that can cause significant pain and disability.
Excision of the tumor can be accomplished with open surgery or, as advocated in
recent years, with computed tomography (CT)-guided radiofrequency ablation. In
this article, a unique arthroscopic approach to excise an osteoid osteoma of the
talus is presented. This was possible by relying on a clear intra-articular
prominent osteophyte, which was used as a landmark to indicate tumor location in
accordance with preoperative CT views. This technique enabled excision of the
tumor with concomitant arthroscopic decompression of the osteophyte, which
contributed to symptoms of anterior ankle impingement.
PMID- 28706841
TI - Technique for Transtibial Knotless Repair of Lateral Meniscus Root Avulsion.
AB - Tear of the meniscal root results in loss of circumferential hoop tension in the
meniscus and increased tibiofemoral contact pressure, leading to cartilage wear.
Repair of the meniscal root can restore function of the meniscus. Many techniques
for root repair have recently been described. We present a technique for root
repair using a transtibial socket and knotless suture technique that can be
performed through standard arthroscopy portals.
PMID- 28706842
TI - Single-Bundle Augmentation for a Partial Tear of the Anterior Cruciate Ligament.
AB - Given the prevalence of anterior cruciate ligament (ACL) tears in young athletes,
it is essential to elucidate and illustrate surgical interventions that return
the most favorable outcomes. Although most ACL injuries are full-thickness tears,
occasionally either the anteromedial (AM) or posterolateral (PL) bundle is torn
in isolation, allowing consideration of an ACL reconstruction or augmentation.
Because the ACL-deficient knee has been shown to exhibit less proprioceptive
feedback, the preservation of the intact bundle may offer an inherent component
of stability. After arthroscopy has confirmed a partial ACL tear, the decision to
augment the intact bundle can be made. The technique is adapted from principles
of the double-bundle reconstruction such that the graft follows the path of
either the native AM bundle or the native PL bundle, depending on the location of
the partial tear. We present our surgical technique for ACL AM bundle
augmentation with PL bundle reconstruction using a semitendinosus tendon
autograft.
PMID- 28706843
TI - A Modification of the Active Compression Test for the Shoulder Biceps-Labrum
Complex.
AB - The active compression test (O'Brien Sign) is widely used by physicians to aid in
the diagnosis of biceps-labrum complex disease. This maneuver has been
particularly criticized in the literature, however, with regard to interobserver
reliability. Criticisms may in fact stem from inaccurate and inconsistent
practice of the examination maneuver, stemming from both patient- and physician
related errors. In this Technical Note, we introduce an easy modification to the
O'Brien Sign that limits such errors and improves test uniformity.
PMID- 28706844
TI - Bankart Repair Using Modern Arthroscopic Technique.
AB - As technology continues to improve, surgeons must regularly re-evaluate
techniques to improve efficacy and outcomes. The Bankart repair for shoulder
instability has evolved from open reconstruction to minimally invasive
arthroscopic techniques, which have the benefit of less pain and morbidity. This
technical description and video present a modern arthroscopic technique for
Bankart repair used at our institution with high success in an athletic
population.
PMID- 28706845
TI - Arthroscopic Triple Arthrodesis in Management of Chronic Flatfoot Deformity.
AB - Triple arthrodesis has a significant role in the management of hindfoot
osteoarthritis and deformity. Traditionally, it is an open procedure with
extensive soft tissue dissection. Arthroscopic triple arthrodesis would appear to
provide good visualization and preparation of the fusion surfaces while
preserving the soft tissue envelope. The purpose of this Technical Note is to
describe a minimally invasive approach of triple arthrodesis to correct chronic
flatfoot deformity.
PMID- 28706846
TI - Arthroscopic Reduction and Fixation of Transverse Intra-articular Glenoid
Fractures With Scapular Extension.
AB - The most common procedure to address transverse glenoid fractures that are
characterized by intra-articular step-off or gapping is open reduction and
internal fixation. Disadvantages of open surgery are delay in regaining full
range of motion, increased approach morbidity, neurovascular complications, and
the need for capsulotomy, which delays healing and increases the risk of
stiffness. An arthroscopically assisted fracture fixation, as described in this
article, is characterized by better visualization of the glenoid articular
surface and reduction of the intra-articular fragments under direct vision, which
diminishes the chances of residual step-off after fixation. Furthermore,
arthroscopic fixation provides the advantages of minimal surgical trauma, which
speeds up the recovery time, decreased morbidity as there is less blood loss
compared with the open technique, lower chance of neurologic injury as there is
less dissection around the spinoglenoid or suprascapular notch, less trauma to
the joint capsule, and lower chances of stiffness and capsulorrhaphy arthropathy.
PMID- 28706847
TI - Endoscopic Synovectomy of Peroneal Tendon Sheath.
AB - Peroneal tenosynovitis usually responds to conservative therapy. Early diagnosis
and management are imperative because improper or delayed diagnosis and treatment
of peroneal tenosynovitis may lead to progression of the tenosynovitis to
peroneal tendon rupture, ultimately limiting the benefit of nonoperative
treatment. For refractory cases, endoscopic tenosynovectomy is indicated. The
purpose of this Technical Note is to report a minimally invasive approach to
perform a synovectomy of zones 1 and 2 of the peroneal tendon sheath.
PMID- 28706848
TI - Bipolar Bone Loss of the Shoulder Joint due to Recurrent Instability: Use of
Fresh Osteochondral Distal Tibia and Humeral Head Allografts.
AB - With increasing shoulder instability events, the likelihood of a bony lesion of
the glenoid and/or humeral head rises. Although bone loss of either the glenoid
or humeral head may result in recurrent instability, bipolar lesions have been
shown, in particular, to result in a negative and additive effect on glenohumeral
stability. In the case of a bipolar lesion comprising severe glenoid bone loss
and an engaging, "off-track" Hill-Sachs lesion, the bony foundation of the
glenohumeral joint is compromised and bony augmentation is necessary. We present
our preferred technique, made up of the application of a distal tibia allograft
to address the glenoid bone loss and humeral head allograft to address the Hill
Sachs lesion, for the treatment of a severe bipolar lesion in the setting of
recurrent anterior shoulder instability after a failed Latarjet procedure.
PMID- 28706849
TI - All-Intra-articular Arthroscopic Rotator Cuff Repair.
AB - This Technical Note presents an arthroscopic technique to repair rotator cuff
tears using a constant intra-articular (glenohumeral) portal for visualization.
The smoothness of both the humeral head cartilage and the articular side of the
rotator cuff offers a cleaner arthroscopic approach, while the absence of a
subacromial bursa also reduces bleeding, turbidity, and the need for iterative
soft tissue debridement. It also facilitates the recognition and repair of
certain tear patterns. The intra-articular perspective allows the surgeon to
visualize how stitches pierce the tissue in a desired and resistant area of the
tendon. During knot tying, instead of watching the knot compressing against the
bursal side of the tendon, the surgeon monitors how the articular side of the
tendon is compressed and attached against the footprint while pushing the knot
until the desired level of reduction is achieved.
PMID- 28706850
TI - Pneumothorax caused by cystic and nodular lung metastases from a malignant
uterine perivascular epithelioid cell tumor (PEComa).
AB - Perivascular epithelioid cell tumors (PEComas) are mesenchymal neoplasms with
immunoreactivity for both melanocytic and smooth muscle markers. PEComas occur at
multiple sites, and malignant PEComas can undergo metastasis, recurrence and
aggressive clinical courses. Although the lung is a common metastatic site of
PEComas, they usually appear as multiple nodules but rarely become cystic or
cavitary. Here, we describe a female patient whose lungs manifested multiple
cystic, cavity-like and nodular metastases 3 years after the resection of uterine
tumors tentatively diagnosed as epithelioid smooth muscle tumors with uncertain
malignant potential. This patient's subsequent pneumothorax necessitated video
assisted thoracoscopic surgery, and examination of her resected lung specimens
eventually led to correcting the diagnosis, i.e., to a PEComa harboring tuberous
sclerosis complex 1 (TSC1) loss-of-heterozygosity that originated in the uterus
and then metastasized to the lungs. The administration of a gonadotropin
releasing hormone analogue later stabilized her clinical course. To the best of
our knowledge, the present case is the first in the literature that associates
PEComas with a TSC1 abnormality. Additionally, the pulmonary manifestations,
including imaging appearance and pneumothorax, somewhat resembled those of
lymphangioleiomyomatosis, a representative disease belonging to the PEComa
family. Although PEComas are rare, clinicians, radiologists and pathologists
should become aware of this disease entity, especially in the combined clinical
setting of multiple cystic, cavity-like, nodular lesions on computed tomography
of the chest and a past history of the tumor in the female reproductive system.
PMID- 28706851
TI - A joint time-frequency analysis of resting-state functional connectivity reveals
novel patterns of connectivity shared between or unique to schizophrenia patients
and healthy controls.
AB - Functional connectivity of the resting-state (RS) brain is a vehicle to study
brain dysconnectivity aspects of diseases such as schizophrenia and bipolar.
Methods that are developed to measure functional connectivity are based on the
underlying hypotheses regarding the actual nature of RS-connectivity including
evidence of temporally dynamic versus static RS-connectivity and evidence of
frequency-specific versus hemodynamically-driven connectivity over a wide
frequency range. This study is derived by these observations of variation of RS
connectivity in temporal and frequency domains and evaluates such characteristics
of RS-connectivity in clinical population and jointly in temporal and frequency
domains (the spectro-temporal domain). We base this study on the hypothesis that
by studying functional connectivity of schizophrenia patients and comparing it to
the one of healthy controls in the spectro-temporal domain we might be able to
make new observations regarding the differences and similarities between diseased
and healthy brain connectivity and such observations could be obscured by studies
which investigate such characteristics separately. Interestingly, our results
include, but are not limited to, a spectrally localized (mostly mid-range
frequencies) modular dynamic connectivity pattern in which sensory motor networks
are anti-correlated with visual, auditory and sub-cortical networks in
schizophrenia, as well as evidence of lagged dependence between default-mode and
sensory networks in schizophrenia. These observations are unique to the proposed
augmented domain of connectivity analysis. We conclude this study by arguing not
only resting-state connectivity has structured spectro-temporal variability, but
also that studying properties of connectivity in this joint domain reveals
distinctive group-based differences and similarities between clinical and healthy
populations.
PMID- 28706852
TI - Neurological software tool for reliable atrophy measurement (NeuroSTREAM) of the
lateral ventricles on clinical-quality T2-FLAIR MRI scans in multiple sclerosis.
AB - BACKGROUND: There is a need for a brain volume measure applicable to the clinical
routine scans. Nearly every multiple sclerosis (MS) protocol includes low
resolution 2D T2-FLAIR imaging. OBJECTIVES: To develop and validate cross
sectional and longitudinal brain atrophy measures on clinical-quality T2-FLAIR
images in MS patients. METHODS: A real-world dataset from 109 MS patients from 62
MRI scanners was used to develop a lateral ventricular volume (LVV) algorithm
with a longitudinal Jacobian-based extension, called NeuroSTREAM. Gold-standard
LVV was calculated on high-resolution T1 1 mm, while NeuroSTREAM LVV was obtained
on low-resolution T2-FLAIR 3 mm thick images. Scan-rescan reliability was
assessed in 5 subjects. The variability of LVV measurement at different field
strengths was tested in 76 healthy controls and 125 MS patients who obtained both
1.5T and 3T scans in 72 hours. Clinical validation of algorithm was performed in
176 MS patients who obtained serial yearly MRI 1.5T scans for 10 years. RESULTS:
Correlation between gold-standard high-resolution T1 LVV and low-resolution T2
FLAIR LVV was r = 0.99, p < 0.001 and the scan-rescan coefficient of variation
was 0.84%. Correlation between low-resolution T2-FLAIR LVV on 1.5T and 3T was r =
0.99, p < 0.001 and the scan-rescan coefficient of variation was 2.69% cross
sectionally and 2.08% via Jacobian integration. NeuroSTREAM showed comparable
effect size (d = 0.39-0.71) in separating MS patients with and without confirmed
disability progression, compared to SIENA and VIENA. CONCLUSIONS: Brain atrophy
measurement on clinical quality T2-FLAIR scans is feasible, accurate, reliable,
and relates to clinical outcomes.
PMID- 28706853
TI - A case of ceftriaxone-associated biliary pseudolithiasis in an elderly patient
with renal dysfunction.
AB - Prior literature suggests that ceftriaxone causes formation of gallbladder stones
at a relatively high frequency, and when abdominal symptoms occur, prompt
investigation of the gallbladder is required with institution of appropriate
treatment. Aging, malnutrition, renal impairment, and sepsis are risk factors for
pseudolithiasis, and prevention of these is important to suppress gallstone
development.
PMID- 28706854
TI - Nocardia beijingensis brain abscesses in an HIV-infected individual.
AB - We describe a case of a 50-year-old Hispanic man diagnosed with HIV/AIDS who
presented with a generalized tonic clonic seizure and ring enhancing cerebral
lesions on imaging. He was initially treated for CNS toxoplasmosis but presented
to the hospital with another tonic clonic seizure despite prescribed therapy.
Brain biopsy was performed which revealed Nocardia beijingensis. He was treated
with intravenous meropenem and trimethoprim/sulfamethoxazole for six weeks
followed by long term oral trimethoprim/sulfamethoxazole with radiographic and
clinical improvement.
PMID- 28706855
TI - A rare case of disseminated Sporothrix schenckii with bone marrow involvement in
a patient with idiopathic CD4 lymphocytopenia.
AB - Sporothrix schenckii is a pathogen with a predilection for dissemination in
immunocompromised individuals, often with HIV. We report a case of disseminated
sporotrichosis in an unfortunate 25 year old male (without HIV) who was
originally treated for presumed pneumonia. The patient continued to worsen
clinically and further work-up eventually revealed Sporothrix schenckii species
with involvement of multiple organs including the skin, heart, lungs and bone
marrow. Despite treatment with multiple antibacterials and antifungals, he
ultimately passed away. This case illustrates the aggressive nature of this
disease along with the importance of early/proper diagnosis and treatment.
PMID- 28706856
TI - Disseminated Nocardia cyriacigeorgia causing pancreatitis in a haploidentical
stem cell transplant recipient.
AB - We report the first published case of acute pancreatitis secondary to
disseminated nocardiosis in a hematopoietic stem cell transplant (HSCT) recipient
on chronic immunosuppression for graft-versus-host disease (GVHD). Nocardiosis in
the HSCT population is relatively rare, and has not yet been described in
haploidentical HSCT recipients. Our patient is a 28-year-old male with a history
of haploidentical HSCT and GVHD of the skin and lung who was admitted to the
hospital with acute pancreatitis. The workup for the etiology of his pancreatitis
was initially unrevealing. He subsequently developed worsening sepsis and
respiratory failure despite broad spectrum antimicrobials. After multiple
bronchoscopies and pancreatic fluid sampling, he was found to have disseminated
nocardiosis with Nocardia cyriacigeorgia.
PMID- 28706857
TI - Synergetic role of integrating the departments of cancer registry and clinical
research at an academic comprehensive cancer center.
AB - Integration of the cancer registry and clinical research departments can have a
significant impact on the accreditation process of a Commission on Cancer (CoC)
Program. Here in we demonstrate that the integration of both departments will
benefit as there is increased knowledge, manpower and crossover in job
responsibilities in our CoC-accredited Academic Comprehensive Cancer Center. In
our model this integration has led to a more successful cooperative interaction
among departments, which has in turn created an enhanced combined effect on
overall output and productivity. More manpower for the cancer registry has led to
increased caseloads, decreased time from date of first contact to abstraction,
quality of data submissions, and timely follow-up of all patients from our
reference date for accurate survival analysis along with completeness of data. In
2016, our Annual Facility report showed an additional 163 cases over prediction
by the state of Maryland Cancer Registry and a 39% increase in case completeness.
As proof of the synergetic effectiveness of our model within one year of its
implementation, the cancer center was able to apply for, and was awarded
membership from Alliance for Clinical Trials in Oncology, Central IRB, and in
turn led to increased clinical trial accrual from 2.8% in 2014 compared to 13.2%
currently. Our cancer registry in year one submitted over 150 more cases than
predicted, improved quality outcome measures displayed by our Cancer Program
Practice Profile reports and had more timely and complete data submissions to
national and state registries. This synergetic integration has led to a better
understanding, utilization and analysis of data by an integrated team with
Clinical Research expertise.
PMID- 28706858
TI - Antioxidants in experimental ischemia-reperfusion injury of the testis: Where are
we heading towards?
AB - Testicular torsion (TT) is a medical emergency that primary affects newborns and
young adolescents. It causes testicular injury due to the torsion of the
spermatic cord and its components, initially in the venous blood flow and finally
in the arterial blood flow. Prompt diagnosis and early surgical management are
necessary in managing this urgent situation. The process of the
pathophysiological events in ischemia-reperfusion is multifactorial and deals
with the perception of the oxidative stress responsible for the consequences of
ischemia/reperfusion (I/R) stress following TT. Duration and severity of torsion
also play a significant role in the oxidative stress. A detrimental result of the
defense system of the testes takes place resulting finally in testicular atrophy
and impaired function. Antioxidant factors have been experimentally studied in an
effort to front this state. They have been classified as endogenous or exogenous
antioxidants. Endogenous antioxidants comprise a structure of enzymic enzymatic
and non-enzymic enzymatic particles presented within cytoplasm and numerous other
subunits in the cells. Exogenous antioxidants include a variety of natural and
pharmaceutical agents that may prevent or ameliorate the harmful effects of I/R
injury. In this study we review those factors and their ability to enhance the
oxidative status of the testis. A feature insight into where we are heading is
attempted.
PMID- 28706859
TI - Role of metabolic stress for enhancing muscle adaptations: Practical
applications.
AB - Metabolic stress is a physiological process that occurs during exercise in
response to low energy that leads to metabolite accumulation [lactate, phosphate
inorganic (Pi) and ions of hydrogen (H+)] in muscle cells. Traditional exercise
protocol (i.e., Resistance training) has an important impact on the increase of
metabolite accumulation, which influences hormonal release, hypoxia, reactive
oxygen species (ROS) production and cell swelling. Changes in acute exercise
routines, such as intensity, volume and rest between sets, are determinants for
the magnitude of metabolic stress, furthermore, different types of training, such
as low-intensity resistance training plus blood flow restriction and high
intensity interval training, could be used to maximize metabolic stress during
exercise. Thus, the objective of this review is to describe practical
applications that induce metabolic stress and the potential effects of metabolic
stress to increase systemic hormonal release, hypoxia, ROS production, cell
swelling and muscle adaptations.
PMID- 28706861
TI - Nutech functional score: A novel scoring system to assess spinal cord injury
patients.
AB - AIM: To develop a new scoring system, nutech functional scores (NFS) for
assessing the patients with spinal cord injury (SCI). METHODS: The conventional
scale, American Spinal Injury Association's (ASIA) impairment scale is a measure
which precisely describes the severity of the SCI. However, it has various
limitations which lead to incomplete assessment of SCI patients. We have
developed a 63 point scoring system, i.e., NFS for patients suffering with SCI. A
list of symptoms either common or rare that were found to be associated with SCI
was recorded for each patient. On the basis of these lists, we have developed
NFS. RESULTS: These lists served as a base to prepare NFS, a 63 point positional
(each symptom is sub-graded and get points based on position) and directional
(moves in direction BAD -> GOOD) scoring system. For non-progressive diseases, 1,
2, 3, 4, 5 denote worst, bad, moderate, good and best (normal), respectively. NFS
for SCI has been divided into different groups based on the affected part of the
body being assessed, i.e., motor assessment (shoulders, elbow, wrist, fingers
grasp, fingers-release, hip, knee, ankle and toe), sensory assessment, autonomic
assessment, bed sore assessment and general assessment. As probability based
studies required a range of (-1, 1) or at least the range of (0, 1) to be useful
for real world analysis, the grades were converted to respective numeric values.
CONCLUSION: NFS can be considered as a unique tool to assess the improvement in
patients with SCI as it overcomes the limitations of ASIA impairment scale.
PMID- 28706860
TI - Targeted temperature management in neurological intensive care unit.
AB - Targeted temperature management (TTM) shows the most promising neuroprotective
therapy against hypoxic/ischemic encephalopathy (HIE). In addition, TTM is also
useful for treatment of elevated intracranial pressure (ICP). HIE and elevated
ICP are common catastrophic conditions in patients admitted in Neurologic
intensive care unit (ICU). The most common cause of HIE is cardiac arrest.
Randomized control trials demonstrate clinical benefits of TTM in patients with
post-cardiac arrest. Although clinical benefit of ICP control by TTM in some
specific critical condition, for an example in traumatic brain injury, is still
controversial, efficacy of ICP control by TTM is confirmed by both in vivo and in
vitro studies. Several methods of TTM have been reported in the literature. TTM
can apply to various clinical conditions associated with hypoxic/ischemic brain
injury and elevated ICP in Neurologic ICU.
PMID- 28706862
TI - Flexible band versus rigid ring annuloplasty for tricuspid regurgitation: a
systematic review and meta-analysis.
AB - BACKGROUND: Up to 20% of patients have pre-discharge residual moderate to severe
tricuspid regurgitation (TR) after tricuspid repair. Reoperations for recurrent
TR carry high mortality rates, which emphasizes the importance of identifying the
optimal technique for the surgical management of TR. The present study is a
systematic review and meta-analysis that aims to compare short and long term
survival and freedom from TR of flexible band ring versus rigid ring for
annuloplasty of TR. METHODS: We conducted a systematic review and meta-analysis
of comparative studies to evaluate these procedures. A systematic search of the
literature was performed from six electronic databases. Pooled meta-analysis was
conducted using odds ratio (OR) and weighted mean difference (WMD). RESULTS: The
rates of in-hospital mortality were not different between the two groups, with
cumulative rates of 6.9% for flexible band and 7.3% for rigid ring (OR: 0.92; 95%
CI: 0.49-1.71). Rates of stroke were also similar with 1.7% of flexible band and
1.3% of rigid rings suffering a perioperative stroke (OR: 1.29; 95% CI: 0.74
2.23). Rigid ring had significantly better freedom from grade >=2 TR at 5 years
(OR: 0.44; 95% CI: 0.20-0.99) and overall (P=0.005). There was no significant
difference in overall rates of reoperation (P=0.232) and survival (P=0.086)
between flexible band and rigid ring. CONCLUSIONS: Both rigid ring and flexible
band offer acceptable outcomes for the treatment of TR. Compared to flexible
band, rates of TR are stable after rigid ring annuloplasty and long term freedom
from TR are superior for rigid ring devices. Large prospective randomized trials
are required in order to validate these findings and assess for improvements in
patient survival.
PMID- 28706863
TI - Non-functional tricuspid valve disease.
AB - Only 75% of severe tricuspid regurgitation is classified as functional, or
related primarily to pulmonary hypertension, right ventricular dysfunction, or a
combination of both. Non-functional tricuspid regurgitation occurs when there is
damage to the tricuspid leaflets, chordae, papillary muscles, or annulus,
independent of right ventricular dysfunction or pulmonary hypertension. The
entities that cause non-functional tricuspid regurgitation include rheumatic and
myxomatous disease, acquired and genetic connective tissue disorders,
endocarditis, sarcoid, pacing, RV biopsy, blunt trauma, radiation, carcinoid,
ergot alkaloids, dopamine agonists, fenfluramine, cardiac tumors, atrial
fibrillation, and congenital malformations. Over time, severe tricuspid
regurgitation that is initially non-functional, can blend into functional
tricuspid regurgitation, related to progressive right ventricular dysfunction.
Symptoms and signs, including a falling right ventricular ejection fraction,
cardiac cirrhosis, ascites, esophageal varices, and anasarca, may occur
insidiously and late, but are associated with substantial morbidity and
mortality. Attempted valve repair or replacement at late stages carries a high
mortality. Crucial to following patients with severe non-functional tricuspid
regurgitation is attention to echo quantification of the tricuspid regurgitation
and right ventricular function, patient symptoms, and the physical examination.
PMID- 28706864
TI - Surgical outcomes of isolated tricuspid valve procedures: repair versus
replacement.
AB - BACKGROUND: Isolated tricuspid valve (ITV) operations are infrequent and the
decision to operate is controversial. We report a series of ITV operations to
outline the current disease status requiring this uncommon procedure with an
emphasis on the results of tricuspid valve repair (TVr) versus replacement (TVR).
METHODS: Using our prospective cardiac surgery database, 57 patients who
underwent ITV operations between 01/02-03/14 were identified. Median follow up
time was 3.5 years [interquartile range (IQR), 0.8-6.7 years]. RESULTS: Fifty
seven patients underwent ITV surgery with a mean age of 54.4+/-14.9 yrs and 61%
were women. Baseline characteristics were similar between patients who underwent
TVr (n=18) or TVR (n=39). The etiologies of TV dysfunction were: ITV endocarditis
14/57 (25%), persistent TV regurgitation after left-sided valve surgery in 12/57
(21%), traumatic biopsies and iatrogenic injury from pacing leads in 11/57 (19%),
orthotopic heart transplant 9/57 (16%), carcinoid syndrome 3/57 (5%), congenital
2/57 (5%) and idiopathic 5/57 (9%). Overall, 32/57 (56%) patients had prior heart
surgery; of which 10/32 (31%) were TV procedures. Bioprosthetic prostheses were
used in 34/39 (87%) patients. Of those who had repair, 11/18 (61%) had ring
annuloplasty, 3/18 (17%) bicuspidization, and 3/18 (17%) De Vega annuloplasty and
one had vegetectomy. Operative mortality was 5.1% (n=2) and 16.7% (n=3) for TVR
and TVr groups, respectively (P=0.32), with an overall mortality rate of 8.6%.
Postoperative complications included new onset renal failure in 6/39 (15%) of TVr
and 2/18 (11%) of TVR (P=0.71) and there were no strokes. Overall survival rates
and degree of residual RV dysfunction were similar for the two groups (both
P=0.3). Five-year survival was 77% and 84% for TVr and TVR respectively (P=0.52).
There was no difference in rates of recurrent tricuspid regurgitation for TVr and
TVR (35.7% vs. 23.5%, respectively, P=0.4). CONCLUSIONS: ITV surgery is
associated with improved but still relatively high operative mortality. Mid-term
outcomes for TVr and TVR are similar with regards to postoperative complications,
survival, and freedom from recurrent tricuspid regurgitation.
PMID- 28706866
TI - Current transcatheter devices to treat functional tricuspid regurgitation with
discussion of issues relevant to clinical trial design.
AB - Functional or secondary tricuspid regurgitation (TR) has seen increased attention
in recent times as relationships with clinically-relevant outcomes have come to
light. Despite the association of increased mortality with significant TR, the
disease remains under-recognized and thus relatively untreated. In addition, the
disease itself has not been extensively studied and the interactions between
annular dilatation, right heart disease and pulmonary hypertension are poorly
understood. However, the high mortality and recurrence rate with current surgical
replacement or repair techniques is well recognised, opening the door to
transcatheter therapies for functional TR. The current perspective reviews the
rationale for transcatheter solutions, describes some of the current approaches
and discusses the ongoing questions of a poorly-studied condition which may limit
the design of clinical trials for this disease.
PMID- 28706867
TI - Tricuspid leaflet repair: innovative solutions.
AB - Tricuspid regurgitation (TR) represents a significant disease process and when
severe, is associated with increased mortality. Recent guidelines support a more
aggressive approach to tricuspid valve (TV) surgery, especially when encountered
with left-sided valvular pathology. While annuloplasty has been the standard
treatment for TR, it may not provide as effective or durable a repair compared to
annuloplasty combined with TV repair techniques. Several of these approaches are
discussed including bicuspidalization, anterior leaflet augmentation, edge to
edge repair, neochords, leaflet resection and combined approaches. Although
patient cohorts in most of the studies examining these techniques are small, the
long-term durability of TV repair is significant.
PMID- 28706868
TI - Tricuspid valve endocarditis.
AB - Right-sided infective endocarditis (RSIE) is less common than left-sided
infective endocarditis (IE), encompassing only 5-10% of cases of IE. Ninety
percent of RSIE involves the tricuspid valve (TV). Given the relatively small
numbers of TVIE cases operated on at most institutions, the purpose of this
review is to highlight and discuss the current understanding of IE involving the
TV. RSIE and TVIE are strongly associated with intravenous drug use (IVDU),
although pacemaker leads, defibrillator leads and vascular access for dialysis
are also major risk factors. Staphylococcus aureus is the predominant causative
organism in TVIE. Most patients with TVIE are successfully treated with
antibiotics, however, 5-16% of RSIE cases eventually require surgical
intervention. Indications and timing for surgery are less clear than for left
sided IE; surgery is primarily considered for failed medical therapy, large
vegetations and septic pulmonary embolism, and less often for TV regurgitation
and heart failure. Most patients with an infected prosthetic TV will require
surgery. Concomitant left-sided IE has its own surgical indications. Earlier
surgical intervention may potentially prevent further destruction of leaflet
tissue and increase the likelihood of TV repair. Fortunately, TV debridement and
repair can be accomplished in most cases, even those with extensive valve
destruction, using a variety of techniques. Valve repair is advocated over
replacement, particularly in IVDUs patients who are young, non-compliant and have
a higher risk of recurrent infection and reoperation with valve replacement.
Excising the valve without replacing, it is not advocated; it has been reported
previously, but these patients are likely to be symptomatic, particularly in
cases with septic pulmonary embolism and increased pulmonary vascular resistance.
Patients with concomitant left-sided involvement have worse prognosis than those
with RSIE alone, due predominantly to greater likelihood of invasion and abscess
formation in left-sided IE. Patients with isolated TVIE have an operative
mortality between 0-15% and excellent survival.
PMID- 28706869
TI - Posterior suture annuloplasty for functional tricuspid regurgitation.
AB - Functional tricuspid regurgitation (TR) is primarily caused by enlargement of the
tricuspid annulus due to right ventricular dilation, frequently secondary to left
sided valvular disease. Early techniques for the treatment of functional TR were
introduced by Jerome Kay in 1965 and Norberto DeVega in 1972. Modified suture
annuloplasty is a modification of DeVega's semicircular purse string technique,
however, it is based on Kay's principle of obliteration of the posterior segment
of the annulus only. While ring annuloplasty is the procedure of choice for
severe functional TR, posterior suture annuloplasty is a technically simpler
option for patients with moderate functional TR.
PMID- 28706870
TI - Management of Ebstein's anomaly.
AB - Ebstein malformation is a rare disease that presents with a spectrum of severity.
We use a management paradigm that breaks the anomaly into two groups: neonates
and children/adults. This leads to a discussion of management and operative
techniques as well as pitfalls. We hope the reader finds our streamlined and
logical approach of benefit to this complex and rare disease.
PMID- 28706871
TI - Tricuspid valve regurgitation after heart transplantation.
AB - Tricuspid valve regurgitation (TVR) in the orthotopic heart transplant (OHT)
recipient is quite common and has varied clinical sequelae. In its severest
forms, it can lead to right-sided failure symptoms indistinguishable from that
seen in native heart TVR disease. While certain implantation techniques are
widely recognized to reduce the risk of TVR in the cardiac allograft, concomitant
tricuspid annuloplasty, while having advocates, is not currently accepted as a
routinely established adjunct. Decisions to surgically correct TVR in the OHT
recipient must be made carefully, as certain clinical scenarios have high risk of
failure. Like in the native heart, anatomic etiologies typically have the
greatest chances for success compared to functional etiologies. While repair
options have been utilized, there is emerging data to support replacement as the
more durable option. While mechanical prostheses are impractical in the heart
transplant recipient, biologic valves offer the advantage of continued access to
the right ventricle for biopsies in addition to acceptable durability in the low
pressure system of the right side.
PMID- 28706872
TI - Surgical management of tricuspid stenosis.
AB - Tricuspid valve stenosis (TS) is rare, affecting less than 1% of patients in
developed nations and approximately 3% of patients worldwide. Detection requires
careful evaluation, as it is almost always associated with left-sided valve
lesions that may obscure its significance. Primary TS is most frequently caused
by rheumatic valvulitis. Other causes include carcinoid, radiation therapy,
infective endocarditis, trauma from endomyocardial biopsy or pacemaker placement,
or congenital abnormalities. Surgical management of TS is not commonly addressed
in standard cardiac texts but is an important topic for the practicing surgeon.
This paper will elucidate the anatomy, pathophysiology, and surgical management
of TS.
PMID- 28706873
TI - Minimal access tricuspid valve surgery.
PMID- 28706874
TI - Ebstein's anomaly-How to correct severe anatomical forms of the defect in adults.
PMID- 28706875
TI - Minimally invasive, beating heart tricuspid valve surgery in a redo case.
PMID- 28706876
TI - Tricuspid valve disease.
PMID- 28706878
TI - A Genetically Modified attenuated Listeria Vaccine Expressing HPV16 E7 Kill Tumor
Cells in Direct and Antigen-Specific Manner.
AB - Attenuated Listeria monocytogenes (L. monocytogenes, LM) induces specific CD8+
and CD4+ T cell responses, and has been identified as a promising cancer vaccine
vector. Cervical cancer is the third most common cancer in women worldwide, with
human papillomavirus (HPV), particularly type 16, being the main etiological
factor. The therapeutic HPV vaccines are urgently needed. The E7 protein of HPV
is necessary for maintaining malignancy in tumor cells. Here, a genetically
modified attenuated LM expressing HPV16 E7 protein was constructed.
Intraperitoneal vaccination of LM4Deltahly::E7 significantly reduced tumor size
and even resulted in complete regression of established tumors in a murine model
of cervical cancer. We provided evidence that recombinant LM strains could enter
the tumor tissue and induce non-specific tumor cell death, probably via
activation of reactive oxygen species and increased intracellular Ca2+ levels.
LM4Deltahly::E7 effectively triggered a strong antigen-specific cellular immunity
in tumor-bearing mice, and elicited significant infiltration of T cells in the
intratumoral milieu. In summary, these data showed LM4Deltahly::E7 to be
effective in a cervical cancer model and LM4Deltahly::E7 induced an antitumor
effect by antigen-specific cellular immune responses and direct killing of tumor
cells, indicating a potential application against cervical cancer.
PMID- 28706877
TI - Protein Lipidation As a Regulator of Apoptotic Calcium Release: Relevance to
Cancer.
AB - Calcium is a critical regulator of cell death pathways. One of the most proximal
events leading to cell death is activation of plasma membrane and endoplasmic
reticulum-resident calcium channels. A large body of evidence indicates that
defects in this pathway contribute to cancer development. Although we have a
thorough understanding of how downstream elevations in cytosolic and
mitochondrial calcium contribute to cell death, it is much less clear how calcium
channels are activated upstream of the apoptotic stimulus. Recently, it has been
shown that protein lipidation is a potent regulator of apoptotic signaling.
Although classically thought of as a static modification, rapid and reversible
protein acylation has emerged as a new signaling paradigm relevant to many
pathways, including calcium release and cell death. In this review, we will
discuss the role of protein lipidation in regulating apoptotic calcium signaling
with direct therapeutic relevance to cancer.
PMID- 28706879
TI - Multiple Substrate Usage of Coxiella burnetii to Feed a Bipartite Metabolic
Network.
AB - The human pathogen Coxiella burnetii causes Q-fever and is classified as a
category B bio-weapon. Exploiting the development of the axenic growth medium
ACCM-2, we have now used 13C-labeling experiments and isotopolog profiling to
investigate the highly diverse metabolic network of C. burnetii. To this aim, C.
burnetii RSA 439 NMII was cultured in ACCM-2 containing 5 mM of either [U
13C3]serine, [U-13C6]glucose, or [U-13C3]glycerol until the late-logarithmic
phase. GC/MS-based isotopolog profiling of protein-derived amino acids, methanol
soluble polar metabolites, fatty acids, and cell wall components (e.g.,
diaminopimelate and sugars) from the labeled bacteria revealed differential
incorporation rates and isotopolog profiles. These data served to decipher the
diverse usages of the labeled substrates and the relative carbon fluxes into the
core metabolism of the pathogen. Whereas, de novo biosynthesis from any of these
substrates could not be found for histidine, isoleucine, leucine, lysine,
phenylalanine, proline and valine, the other amino acids and metabolites under
study acquired 13C-label at specific rates depending on the nature of the tracer
compound. Glucose was directly used for cell wall biosynthesis, but was also
converted into pyruvate (and its downstream metabolites) through the glycolytic
pathway or into erythrose 4-phosphate (e.g., for the biosynthesis of tyrosine)
via the non-oxidative pentose phosphate pathway. Glycerol efficiently served as a
gluconeogenetic substrate and could also be used via phosphoenolpyruvate and
diaminopimelate as a major carbon source for cell wall biosynthesis. In contrast,
exogenous serine was mainly utilized in downstream metabolic processes, e.g., via
acetyl-CoA in a complete citrate cycle with fluxes in the oxidative direction and
as a carbon feed for fatty acid biosynthesis. In summary, the data reflect
multiple and differential substrate usages by C. burnetii in a bipartite-type
metabolic network, resembling the overall topology of the related pathogen
Legionella pneumophila. These strategies could benefit the metabolic capacities
of the pathogens also as a trait to adapt for replication under intracellular
conditions.
PMID- 28706880
TI - A Novel Method for the Management of Anophthalmic Socket.
AB - An orbital defect causes severe facial asymmetry and disfigurement that result in
an immense emotional trauma to the patient and is also associated with economic,
esthetic, and psychological problems. A prosthetic replacement is the treatment
of choice in helping individual to return to his normal life by producing an
acceptable and lifelike appearance. This case report describes the critical areas
of fabrication of ocular prosthesis for a patient with missing right eye due to
trauma to eye ball in an accident. Patient had given a history of surgical
enucleation of the eye 15 days after ocular trauma. A polymethyl methacrylate
ocular prosthesis was planned. The technique described in this case report
presents the use of both custom-made and stock eye shell in an attempt to include
the benefits of both. A novel attempt was made to simulate eye movements and
exact color matching to that of contralateral eye to provide a better and
functional ocular prosthesis to the patient.
PMID- 28706881
TI - Assessment Effects of Resveratrol on Human Telomerase Reverse Transcriptase
Messenger Ribonucleic Acid Transcript in Human Glioblastoma.
AB - BACKGROUND: Glioblastoma (GBM) is the most common and aggressive brain tumor,
which has a poor prognosis despite the advent of different therapeutic
strategies. There are numerous molecular biomarkers to contribute diagnosis,
prognosis, and prediction of response to the current therapy in GBM. One of the
most important markers that are potentially valuable is immortalization-specific
or immortalization-associated marker named "hTERT messenger ribonucleic acid
(mRNA)" the key subunit of telomerase enzyme, which is expressed in more than 85%
of cancer cells, in spite of the majority of normal somatic cells. In this study,
we investigated the effects of resveratrol (RSV) on this mRNA marker level,
leading to cancer progression. MATERIALS AND METHODS: U-87MG cell line was
obtained from Pasteur Institute of Iran and treated with various concentrations
of 0-160 MUg/mL of RSV and at different time points (24, 48, and 72 h). To
evaluate viability of U-87MG cells, standard 3-(4,5-dimethylthiazol-2-yl)-2,5
diphenyltetrazolium bromide assay was performed. Real-time polymerase chain
reaction (RT-PCR) was used for comparative and quantitative assessment of human
telomerase reverse transcriptase (hTERT) mRNA copy number versus control
untreated group. RESULTS: The results of our investigation suggested that RSV
effectively inhibited cell growth and caused cell death in dose-dependent (P <
0.05) and not in time-dependent manner (P > 0.05), in vitro. Interestingly,
quantitative RT-PCR analysis demonstrated that at half inhibition concentration,
RSV dramatically decreased mRNA expression of hTERT, the catalytic subunit of
telomerase enzyme, which leads to prevention of cell division and tumor
progression. CONCLUSION: With regard to downregulation of this immortalization
associated marker, RSV may potentially be used as a therapeutic agent against
GBM.
PMID- 28706882
TI - Distribution of the Strains of Multidrug-resistant, Extensively Drug-resistant,
and Pandrug-resistant Pseudomonas aeruginosa Isolates from Burn Patients.
AB - BACKGROUND: Pseudomonas aeruginosa is an opportunistic and Gram-negative pathogen
that is used as the most important factor in burn wound infections, and due to
the rapid acquisition of multidrug resistance (MDR), it causes high mortality
rates in these sectors. Thus, diagnosis and assessment of antibiotic resistance
patterns are very important in these patients. The aim of this study was to
evaluate antibiotic resistance pattern and determining P. aeruginosa MDR.
MATERIALS AND METHODS: In this study, phenotypic, biochemical, and polymerase
chain reaction tests were used to identify P. aeruginosa from 120 wound burn
samples that 96 samples were detected to P. aeruginosa species. In the next step,
according to the Clinical and Laboratory Standard Institute standard guidelines,
antibiogram test was performed by disk diffusion method for amikacin,
ciprofloxacin, norfloxacin, gentamicin, cefepime, aztreonam, meropenem, colistin,
ceftazidime, and piperacillin-tazobactam antibiotics. Antibiotic data were
analyzed by WHONET software; finally, the rate of antibiotic resistance and MDR
strains was determined. RESULTS: The highest antibiotic resistance belonged to
amikacin (94.8%) and norfloxacin (90.6%); in contrast, colistin (8.3%) had the
lowest and the MDR strains were MDR (95.8%) and extensively drug resistance (XDR)
(87.5%). CONCLUSION: In this study, there was MDR with an alarming rate including
MDR (95.8%), XDR (87.5%), and pan-drug resistance (0%). As a result, given
antibiotics to patients should be controlled by the antibiogram results to avoid
increasing MDR strains.
PMID- 28706883
TI - Effects of Mannitol 20% on Outcomes in Nontraumatic Intracerebral Hemorrhage.
AB - BACKGROUND: A large number of stroke patients are not the perfect candidate for
craniotomy and invasive procedures, so providing an alternative and noninvasive
method, which is applicable in terms of costs and facilities, is necessary. Thus,
the present study aimed to determine the effects of mannitol 20% on outcome of
the patients with nontraumatic intracerebral hemorrhage (ICH) in patients
admitted to Isfahan's Al-Zahra Hospital during 2012 and 2013. MATERIALS AND
METHODS: This is a clinical trial study which is conducted during 2012-2013 in
Isfahan's Al-Zahra Hospital. In this study, 41 patients suffering from ICH
received mannitol 20% for 3 days, and volume of hemorrhage and Glasgow Coma Scale
(GCS) of patients were controlled every 12 h. The collected data were analyzed
via SPSS software. RESULTS: The mean ICH volume was 22.1 +/- 6.3 ml in pre
intervention and 38.4 +/- 19.3 ml in post intervention, and according to the t
paired test, before and after treatment the difference was significant (P <
0.001). Hemorrhage volume was stable in nine patients (22%), it increased in 25
patients (61%), and decreased in seven patients (17.1%). The mean index of GCS
before and after treatment was 11.85 +/- 1.6 and 9.37 +/- 2.65, respectively.
Moreover according to t-paired test, the difference was significant before and
after treatment (P < 0.001). During using mannitol, the GCS index was stable in
eight patients (19.5%), it increased in eight patients (19.5%) and decreased in
25 patients (61%). CONCLUSIONS: Mannitol injection was not effective in reducing
hemorrhage size, and its use is not recommended, also, further studies in this
field have been proposed.
PMID- 28706884
TI - Cytotoxic Evaluation of Some Fused Pyridazino- and Pyrrolo-quinazolinones
Derivatives on Melanoma and Prostate Cell Lines.
AB - BACKGROUND: Quinazolinon as an important class of heterocycles is attractive in
medicinal research areas due to their wide range of biological effects. Cytotoxic
activities of the quinazolinone derivatives in various cell lines including:
HeLa, L1210 (mouse lymphocytic leukemia) and HT29 (human colon adenocarcinoma)
were reported. MATERIALS AND METHODS: In this study, a number of newly made
tricycles quinazolinone derivatives such as fused pyridazino-quinazolinones and
fused pyrrolo-quinazolinones were evaluated on two cancerous cell lines, melanoma
(B16F10) and prostate (PC3) using the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl
tetrazolium bromide colorimetric assay. RESULTS: The results of cytotoxicity
evaluations indicated that almost all of the compounds at the concentrations of
10 and 100 MUM showed significant differences in viability in comparison with
negative control at 48 h exposure (P < 0.05). However, during 24 h exposure some
of the compounds showed cytotoxicity activity. CONCLUSION: Results showed that
both cell lines were sensitive to synthesized compounds and longer duration of
exposure (48 h) had better results compared to that of 24 h screening.
PMID- 28706885
TI - Omega-3 fatty acids inhibit oxidative stress in a rat model of liver
regeneration.
AB - PURPOSE: Lipid peroxidation and consequent reactive oxygen species in the setting
of oxidative stress have crucial roles in liver regeneration, which may adversely
affect the regeneration itself and lead to liver failure. The aim of the current
study is to investigate whether omega-3 fatty acid supplementation inhibits
oxidative stress in an experimental model of liver regeneration. METHODS: Forty
rats were allocated to four groups. Rats in group A received a sham operation.
Rats in group B were subjected to right portal vein ligation (RPVL) and saline
infusion. Rats in groups C and D were subjected to RPVL and total parenteral
nutrition (TPN) with an all-in-one admixture containing a soybean oil based lipid
emulsion. Rats in group D were additionally supplemented with omega-3 fatty acid
infusion. Oxidative stresses in the blood and liver were measured by glutathione,
superoxide dismutase, catalase, glutathione peroxidase, malondialdehyde, and
nitric oxide. RESULTS: Omega-3 supplementation to the TPN solution significantly
corrected alterations in the blood and tissue concentrations of oxidants and anti
oxidants during regeneration (P < 0.05). CONCLUSION: Omega-3 fatty acid
supplementation to the TPN solution revealed promising results in removal of
oxidative stress that emerges during liver regeneration.
PMID- 28706886
TI - The effects of indoxyl sulfate-induced endothelial microparticles on neointimal
hyperplasia formation in an ex vivo model.
AB - PURPOSE: Neointimal hyperplasia (NH) is considered to be one of the main causes
of vascular access occlusion in patients receiving hemodialysis. Endothelial
injury and TGF-beta-mediated proliferation of vascular smooth muscle cells
(VSMCs) induce NH. Endothelial microparticles (EMPs) are also increased by
endothelial injury. We aimed to investigate the effects of EMPs and TGF-beta
expression on VSMC proliferation and their contributions to NH formation in an ex
vivo model. METHODS: EMPs were collected from the culture media of human
umbilical vein endothelial cells treated with indoxyl sulfate (IS, 250 ug/mL)
after ultracentrifugation at 100,000 * g. Porcine internal jugular veins were
isolated and treated with EMPs (2 * 106 /mL) or left untreated for 12 days and
subsequently compared with TGF-beta (10 ng/mL)-treated venous tissue. Intima
media thickness and NH area were assessed using a digital program. Masson's
trichrome staining and immunohistochemistry (IHC) analysis for alpha-smooth
muscle actin, phosphorylated Akt, ERK1/2, p38 mitogen-activated protein kinase
(MAPK), and Smad3 were performed on each vein sample. RESULTS: NH and VSMC
proliferation developed to a significantly greater degree in EMP-treated veins
compared to controls, with similar patterns seen in TGF-beta-stimulated samples.
IHC analysis demonstrated that EMPs markedly increased phosphorylation of Akt,
ERK1/2, p38 MAPK, and Smad3 in areas of venous NH formation. CONCLUSION: Our
results showed that IS-induced EMPs provoked massive VSMC proliferation and NH
formation via activation of the TGF-beta signaling pathways. Further
investigation is needed to elucidate the precise mechanism of EMP activity on
vascular access stenosis in vivo.
PMID- 28706887
TI - Associations between gene expression profiles of invasive breast cancer and
Breast Imaging Reporting and Data System MRI lexicon.
AB - PURPOSE: To evaluate whether the Breast Imaging Reporting and Data System (BI
RADS) MRI lexicon could reflect the genomic information of breast cancers and to
suggest intuitive imaging features as biomarkers. METHODS: Matched breast MRI
data from The Cancer Imaging Archive and gene expression profile from The Cancer
Genome Atlas of 70 invasive breast cancers were analyzed. Magnetic resonance
images were reviewed according to the BI-RADS MRI lexicon of mass morphology. The
cancers were divided into 2 groups of gene clustering by gene set enrichment an
alysis. Clinicopathologic and imaging characteristics were compared between the 2
groups. RESULTS: The luminal subtype was predominant in the group 1 gene set and
the triple-negative subtype was predominant in the group 2 gene set (55 of 56,
98.2% vs. 9 of 14, 64.3%). Internal enhancement descriptors were different
between the 2 groups; heterogeneity was most frequent in group 1 (27 of 56,
48.2%) and rim enhancement was dominant in group 2 (10 of 14, 71.4%). In group 1,
the gene sets related to mammary gland development were overexpressed whereas the
gene sets related to mitotic cell division were overexpressed in group 2.
CONCLUSION: We identified intuitive imaging features of breast MRI associated
with distinct gene expression profiles using the standard imaging variables of BI
RADS. The internal enhancement pattern on MRI might reflect specific gene
expression profiles of breast cancers, which can be recognized by visual
distinction.
PMID- 28706888
TI - Comparison of the outcomes of robotic cholecystectomy and laparoscopic
cholecystectomy.
AB - PURPOSE: This study compared the effects of robotic single-port cholecystectomy
(RC) and 3-port laparoscopic cholecystectomy (LC) on patients' surgical pain,
postoperative complications, and satisfaction. METHODS: One hundred twenty
patients with gallbladder disease scheduled for either LC or RC were recruited.
Each patient was followed up for 1 week after hospital discharge. RESULTS: Time
stayed in operating room was longer in patients with RC, however their hospital
stay was shorter than those with LC (t = 3.01, P = 0.003). Since patients with RC
received more analgesics during the surgery (t = 3.98, P < 0.001), all
participants' surgical pain level were analyzed by using analysis of covariance.
Patients who underwent RC reported less surgical pain consistently at 6 hours and
first day after surgery and 2 days and 1 week later than patients in the LC.
Repeated measure analysis of variance also demonstrated that the RC with single
port might cause less pain throughout the postoperative period (F = 25.68, P <
0.001). Participants' conditions appeared stable without complications such as
infection or bleeding regardless of the surgical type however, overall
satisfaction with RC showed significantly higher than those with LC except for
one item, "the cost of surgery." CONCLUSION: These results suggested that the RC
might be a better choice for people who concern about surgical pain and early
hospital discharge. Since there were no differences in postoperative health
status between the 2 groups, health care providers as an advocate can provide
more reliable information to their patients.
PMID- 28706889
TI - Long-term oncologic outcomes of laparoscopic surgery for splenic flexure colon
cancer are comparable to conventional open surgery.
AB - PURPOSE: Few studies about laparoscopic surgery for splenic flexure colon cancer
have been published. This study aims to compare the short- and long-term outcomes
of laparoscopic surgery for splenic flexure colon cancer with those of
conventional open surgery. METHODS: From January 2004 to December 2010, 51
consecutive patients who underwent curative resection for stages I-III splenic
flexure colon cancer were enrolled. Thirty-three patients underwent laparoscopy
assisted colectomy, while 18 patients underwent conventional open colectomy.
Short- and long-term outcomes of the 2 groups were compared. RESULTS: There were
no differences in baseline characteristics, intra- and postoperative
complications. The laparoscopy group showed longer operation time (median
[interquartile range, IQR]: 295.0 [255.0-362.5] minutes vs. 180.0 [168.8-206.3]
minutes, P < 0.001). In the laparoscopy group, return of bowel function was
faster (median [IQR]: 3 [2-4] vs. 4 [3-5], P = 0.007) and postoperative hospital
stay was shorter (median [IQR]: 9 [8-11] vs. 10.5 [9-19], P = 0.026). There were
no statistically significant differences in overall survival rate (84.3% vs.
76.0%, P = 0.560) or disease-free survival rate (93.8% vs. 74.5%, P = 0.078)
between the 2 groups. CONCLUSION: Laparoscopic surgery for splenic flexure colon
cancer has better short-term outcomes than open surgery, as well as acceptable
long-term outcomes. Laparoscopic surgery can be a safe and feasible alternative
to conventional open surgery for splenic flexure colon cancer.
PMID- 28706890
TI - Clinical implication of discrepancies between surgical and pathologic diagnoses
of acute appendicitis.
AB - PURPOSE: The postoperative treatment after appendectomy is usually decided on the
basis of the surgeons' intraoperative findings. Comparatively, the pathologic
diagnosis of appendicitis is confirmed several days after the surgery; therefore,
it usually does not affect the postoperative treatment strategy. The aim of this
study was to investigate the discrepancies between the surgical and pathologic
diagnoses of appendicitis and to identify their clinical implication. METHODS: A
retrospective observational study was performed in 1,817 patients who underwent 3
port laparoscopic appendectomy for the final diagnosis of appendicitis. The
clinical variables that could estimate the severity of appendicitis and the
intensity of postoperative treatment were analyzed and compared according to the
surgical and pathologic diagnoses. RESULTS: Of 1,321 cases of surgically simple
appendicitis, 254 (29.3%) were pathologically complicated appendicitis. On the
other hand, 221 of 496 cases (44.5%) of surgically complicated appendicitis were
pathologically simple. Neither the surgical nor the pathologic diagnosis of
appendicitis affected the development of postoperative intra-abdominal abscess (P
= 0.079 for surgical diagnosis; P = 0.288 for pathologic diagnosis); however, the
surgical diagnosis showed more correlation with the severity of disease and the
intensity of the treatment pathway than did the pathologic diagnosis. CONCLUSION:
There were discrepancies between the surgeons' intraoperative assessment and the
pathologists' final histologic diagnosis of appendicitis. The surgeon's
classification might be more predictive of the outcome than the pathologist's
because only the surgeon's findings are available immediately after surgery.
PMID- 28706891
TI - Evaluation of botulinum toxin type A effectiveness in preventing postoperative
intraperitoneal adhesions.
AB - PURPOSE: Postoperative intraperitoneal adhesions (PIAs) are one of the most
important problems surgeons have to face after laparotomies. In this study, we
aimed to evaluate the effectiveness of local application of botulinum toxin type
A (BoNT-A) in various dosages on the prevention of intra-abdominal adhesions in
rats with experimental intra-abdominal adhesions. METHODS: Forty Wistar Albino
female rats were randomly separated into 4 groups. The 4 groups were determined
as follows: Control (group 1, n = 10); Sham (group 2, n = 10); 10-ug/kg low-dose
BoNT-A (group 3, n = 10) and 30-ug/kg high-dose BoNT-A (group 4, n = 10).
Subserosal injuries were created on the caecum of all rats. Laparotomy was
performed on the fifth day. Adhesion scores, histopathological examination, and E
cadherin expression levels were evaluated. RESULTS: General adhesion scores for
groups 1 and 2 were determined to be significantly high when compared to group 4
(P < 0.001). A significant difference was also determined between groups 3 and 4
in terms of general adhesion scores (P < 0.05). In pair comparisons, a
significant decrease in high-dose BoNT-A group (group 4) when compared to groups
1 and 2 in terms of neovascularization, fibroblast density, collagen deposition
and inflammatory cell count was determined (P < 0.05). CONCLUSION: A significant
decrease was observed only in postoperative PIAs in the high-dose BoNT-A group
between all 4 rat-groups with experimentally created postoperative PIAs. In this
study, high-dose BoNT-A is determined to be an effective agent in preventing
postoperative PIAs.
PMID- 28706892
TI - Primary osteosarcoma of the breast: a case report.
AB - Primary osteosarcomas of the breast are extremely uncommon. Here we describe a
case of a 77-year-old woman who presented with a hard mass on her right breast.
Mammography and breast ultrasound demonstrated a round-shaped calcified mass on
the right breast but the features were not definitely diagnostic. For diagnostic
purposes, an excisional biopsy was performed and the mass proved to be a primary
osteosarcoma of the breast by pathologic findings. PET-CT and whole body bone
scan showed neither evidence of metastasis nor underlying bone lesions. Wide
excision without axillary lymph node dissection was performed after diagnosis.
Further treatment such as adjuvant chemotherapy or radiation therapy was not
performed. We discuss proper treatment of this rare type of breast cancer.
PMID- 28706893
TI - Rectal perforation by compressed air.
AB - As the use of compressed air in industrial work has increased, so has the risk of
associated pneumatic injury from its improper use. However, damage of large
intestine caused by compressed air is uncommon. Herein a case of pneumatic
rupture of the rectum is described. The patient was admitted to the Emergency
Room complaining of abdominal pain and distension. His colleague triggered a
compressed air nozzle over his buttock. On arrival, vital signs were stable but
physical examination revealed peritoneal irritation and marked distension of the
abdomen. Computed tomography showed a large volume of air in the peritoneal
cavity and subcutaneous emphysema at the perineum. A rectal perforation was found
at laparotomy and the Hartmann procedure was performed.
PMID- 28706894
TI - Developmental Origins and Nephron Endowment in Hypertension.
AB - Primary hypertension continues to be one of the main risk factors for
cardiovascular disease worldwide. A stable intrauterine environment is critical
for the future development and health of the fetus. The developing kidney has
been found to be especially vulnerable during this time period, and
epidemiological studies have demonstrated that an adverse in utero environment is
associated with an increased risk of hypertension and chronic kidney disease.
Macro- and micronutrient deficiencies as well as exposure to tobacco, alcohol,
and certain medications during gestation have been shown to negatively impact
nephrogenesis and reduce one's nephron number. In 1988, Brenner et al. put forth
the controversial hypothesis that a reduced nephron complement is a risk factor
for hypertension and chronic kidney disease in adulthood. Since then numerous
animal and human studies have confirmed this relationship demonstrating that
there is an inverse association between blood pressure and nephron number. As our
understanding of the developmental programming of hypertension and other non
communicable diseases improves, more effective preventive health measures can be
developed in the future.
PMID- 28706895
TI - Beyond One Health-Zoological Medicine in the Anthropocene.
PMID- 28706896
TI - Growth Characterization of Single and Double Salmonella Methionine Auxotroph
Strains for Potential Vaccine Use in Poultry.
AB - Poultry meat is an important source of zoonotic Salmonella infection. Oral
vaccination of chickens with live attenuated Salmonella during grow-out is an
attractive approach to control Salmonella colonization in the chicken
gastrointestinal tract. In this study, we report the construction of methionine
dependent and growth of Salmonella Typhimurium mutant strains with methionine
auxotrophy (DeltametR and DeltaDeltametRmetD) and survival in chicken feed and
fecal matrices. The methionine auxotroph mutant DeltaDeltametRmetD grew slowly on
L-methionine but failed to grow on D-methionine, as expected, and exhibited lower
affinity for methionine compared with the isogenic parent strain (DeltametR
single mutant) in whole-cell affinity experiments. Preliminary data conducted as
part of a previously published bird challenge study indicated that the methionine
auxotroph was less effective at protection in chickens to a challenge with
virulent wild-type parent strain but generated greater Salmonella-specific serum
IgG. Although the auxotroph could not sustain itself in minimal media it was able
to survive when incubated in the presence of chicken and fecal material. The
immune response appears promising but further work may be needed to alter low
affinity methionine transporters and methionine biosynthesis genes in combination
with the knock-out of the high affinity transporter metD reported here to ensure
timely clearance of the candidate vaccine strain.
PMID- 28706897
TI - Special issue: mesothelioma.
PMID- 28706898
TI - The impact of surgical approach on quality of life for pleural malignant
mesothelioma.
AB - BACKGROUND: A comprehensive review of quality of life (QoL) after surgery for
malignant pleural mesothelioma (MPM) was conducted to assess differences between
pleurectomy decortication (P/D) and extrapleural pneumonectomy (EPP). METHODS:
Original research studies on quality of life after mesothelioma surgery were
identified through June 2016; 15 articles and 12 distinct datasets, for a total
of 523 patients, were retrieved. RESULTS: QoL data was available for 102 patients
treated with EPP and 296 with P/D. Two studies directly compared QoL outcomes
between the two techniques. Symptoms, lung function parameters, and physical and
social functioning were still compromised 6 months following surgery. However,
P/D patients fared better than EPP patients across QoL measures. CONCLUSIONS:
Quality of life is generally better for patients undergoing P/D compared to EPP,
for an extended period following surgery. Given the need for multimodality
therapy and the aggressive nature of MPM, QoL outcomes should be strongly
considered when recommending type of surgery for patients with this disease.
PMID- 28706899
TI - Intra-abdominal manifestations of pleural mesothelioma.
AB - Malignant pleural mesothelioma is a disease characterized by persistent and
progressive disease within the hemithorax. However, after aggressive local
regional treatment using surgery, regional chemotherapy, radiation therapy, and
systemic chemotherapy, metastases outside of the pleural space may become the
chief obstacle to long-term survival. One possible direction of cancer
dissemination is direct extension through the hemidiaphragm into the peritoneal
space by the disease itself or as a result of diaphragm resection. In those
patients who have isolated progression of disease within the peritoneal space,
evaluation of their clinical condition using prognostic indicators is essential.
Patients with a limited extent of disease and favorable radiologic findings by CT
should be considered for cytoreductive surgery using peritonectomy procedures and
perioperative combined intraperitoneal and systemic chemotherapy. Although few
patients with pleural to peritoneal disease extension have been treated, some
favorable long-term results suggest that selected patients should be thoroughly
evaluated for disease control within the abdominal and pelvic space.
PMID- 28706900
TI - Extrapleural pneumonectomy (EPP) vs. pleurectomy decortication (P/D).
AB - Surgical techniques for treatment of malignant pleural mesothelioma (MPM) have
improved over the decades. The main surgical principle was accepted as
macroscopic complete resection. This principle was achieved with extrapleural
pneumonectomy (EPP) and extended pleurectomy/decortication (P/D). Mortality and
morbidity are higher following EPP with supraventricular arrhythmias, pulmonary
embolism, bronchopleural fistula and pulmonary failure being the most common,
while prolonged air leak is frequent following P/D. Completion of multimodality
treatment was also shown to be a prognostic factor. Many different neoadjuvant
and adjuvant protocols were applied with limited effect on prognosis. While
locoregional recurrence is more common following P/D, EPP patients typically
recur in contralateral hemithorax and abdomen. Hemithoracic radiation following
EPP was the only effective technique shown to decrease locoregional recurrence.
However, neither surgical technique (EPP vs. P/D), nor types of multimodality
treatment protocols were found to be prognostic in MPM. Epithelioid histology,
metastasis to extrapleural lymph nodes and completion of multimodality treatment
were prognostic in most of the series. In conclusion, based on the current
evidence, the choice of a less morbid and mortal procedure (P/D) seems to be the
logical choice in the treatment of MPM.
PMID- 28706901
TI - Intraoperative intracavitary hyperthermic chemotherapy for malignant pleural
mesothelioma.
AB - Malignant pleural mesothelioma (MPM) is a dreadful disease with a poor prognosis.
Multimodality therapy including surgical macroscopic complete resection is
performed to treat operable MPM. Intraoperative intracavitary hyperthermic
chemotherapy for MPM was reviewed. Appropriate papers published between 2006 and
present were extracted by the PubMed advanced search by MPM (Title/Abstract),
chemotherapy (Title/Abstract), and hyperthermia (All fields). Among the selected
papers, those written in English, and treated more than ten MPM patients were
reviewed. The intraoperative intracavitary hyperthermic chemotherapy has been
performed following extrapleural pneumonectomy (EPP) or pleurectomy/decortication
(P/D) for MPM. Cisplatin was mainly used for perfusion, and the morbidity and
mortality was acceptable. In conclusion, the intraoperative intracavitary
hyperthermic chemotherapy following EPP or P/D for MPM might enhance local
control in the chest cavity.
PMID- 28706902
TI - Environmental asbestos exposure and risk of mesothelioma.
AB - Mesothelioma is commonly considered an occupational disease occurring as a result
of asbestos exposure in the workplace. Several avenues for environmental asbestos
exposures have been described and may be associated with asbestos related
disease, including mesothelioma. Worker take-home asbestos, or para-occupational
exposure, has been well documented and is the most commonly reported pathway for
asbestos exposure among mesothelioma cases that do not have history of
occupational asbestos exposure. Observational studies have evaluated several
communities with elevated mesothelioma incidence and environmental exposures
attributed to local asbestos-related industries. Potential, but uncertain,
mesothelioma risk also may be associated with general population asbestos
exposure through contact with asbestos-containing commercial products,
particularly housing materials that can be easily disturbed through normal
activity. Finally, studies have described elevated mesothelioma incidence in
several areas where populations are exposed to naturally occurring asbestos
materials. These various environmental asbestos exposure pathways are poorly
understood, and further studies should be pursued to evaluate their respective
importance for population mesothelioma risk.
PMID- 28706903
TI - Overview of treatment related complications in malignant pleural mesothelioma.
AB - Malignant pleural mesothelioma (MPM) is an aggressive malignant neoplasm of the
pleura related to asbestos exposure. Despite recent advances in therapy for MPM,
the prognosis remains poor, with considerable treatment associated morbidity.
Radiological assessment plays a central role in the timely identification and
subsequent management of treatment related complications in MPM. This review
highlights common and uncommon complications associated with and encountered in
the post treatment phase.
PMID- 28706904
TI - Malignant peritoneal mesothelioma: a review.
AB - Mesothelioma is a malignancy of serosal membranes. It is most commonly
encountered in the visceral pleura with the second most common location in the
peritoneum. The diagnosis is very rare and has been linked to toxic exposure to
industrial pollutants, especially asbestos. Malignant peritoneal mesothelioma
(MPM) commonly presents with diffuse, extensive spread throughout the abdomen
with rare metastatic spread beyond the abdominal cavity. Due to its rarity and
nonspecific symptoms, it is usually diagnosed late when the disease burden is
extensive. Because pleural mesothelioma is more common than MPM, most research
has been on the pleural variant and extrapolated for MPM. While treatment
advances have been made for MPM, the disease is universally fatal from either
abdominal complications secondary to the spread of disease or starvation.
Untreated, the life expectancy is less than a year. Cytoreductive surgery (CRS)
with heated intraperitoneal chemotherapy (HIPEC) has become the mainstay of
therapy with systemic therapies still being developed. We will review the
epidemiology of MPM and discuss diagnostic and treatment strategies.
PMID- 28706905
TI - A nuanced view of extrapleural pneumonectomy for malignant pleural mesothelioma.
AB - Multimodality treatment including macroscopic complete resection (MCR) is
currently the most effective therapy for patients with malignant pleural
mesothelioma (MPM). However, the allocation to one of the possible combinations
has to be discussed individually since various factors influence the decision
making process. In the past years, relevant new information about the disease and
the outcome of different treatment modalities have been generated, which allows a
more individual allocation to the best treatment. For many years extrapleural
pneumonectomy (EPP)-the most aggressive procedure to achieve a MCR-was the first
choice in combination with adjuvant or neo-adjuvant chemotherapy and radiation
therapy for all patients except those with minimal disease. However, mortality
and morbidity of an EPP and the fact, that even with the most radical procedure
only MCR and not a complete resection can be achieved, led to shift towards
pleurectomy/decortication in most of the centers. But also today, EPP is still a
valuable option in selected cases and the entire treatment concept requires a
nuanced view, which will be discussed in this review.
PMID- 28706906
TI - Mesothelioma: recent highlights.
AB - Recent discoveries have elucidated some of the mechanisms responsible for the
development of mesothelioma. These discoveries are: (I) the critical role of
chronic inflammation in promoting mesothelioma growth, driven by the release of
high mobility group box protein-1 (HMGB1) following asbestos deposition in
tissues and its potential role as a biomarker to identify asbestos exposed
individuals and mesothelioma patients; (II) the discovery that inherited
heterozygous germline mutations of the deubiquitylase BRCA-associated protein 1
(BAP1) cause a high incidence of mesothelioma in some families; and that (III)
germline BAP1 mutations lower the threshold of asbestos required to cause
mesothelioma in mice, evidence of gene X environment interaction. These findings
together with the identification of novel serum biomarkers, including HMGB1,
Fibulin-3, etc., promise to revolutionize screening and treatment of this
malignancy in the coming years.
PMID- 28706907
TI - The Cappadocia mesothelioma epidemic: its influence in Turkey and abroad.
AB - The epidemic of mesothelioma in Cappadocia, Turkey, is unprecedented in medical
history. In three Cappadocian villages, Karain, Tuzkoy and "old" Sarihidir, about
50% of all deaths (including neonatal deaths and traffic fatalities) have been
caused by mesothelioma. No other epidemic in medical history has caused such a
high incidence of death. This is even more unusual when considering that (I)
epidemics are caused by infectious agents, not cancer, and (II) mesothelioma is a
rare cancer. World-wide mesothelioma incidence varies between 1/106 in areas with
no asbestos industry to about 10-30/106 in areas with asbestos industry. This
article reviews how the mesothelioma epidemic was discovered in Cappadocia by Dr.
Baris (my mentor), how we initially linked the epidemic to erionite exposure, and
later (with Dr. Carbone) to the interaction between genetic predisposition and
environmental exposure. Our team's work had an important positive impact on the
lives of those living in Cappadocia and also in many genetically predisposed
families living around the world. I will discuss how the work that started in
three remote Cappadocian villages led to the award of a NCI P01 grant to support
our studies. Our studies proved that genetics modulates mineral fiber
carcinogenesis and led to the discovery that carriers of germline BAP1 mutations
have a very high risk of developing mesothelioma and other malignancies. A new,
very active field of research developed following our discoveries to elucidate
the mechanism by which BAP1 modulates mineral fiber carcinogenesis as well as to
identify additional genes that when mutated increase the risk of mesothelioma and
other environmentally related cancers. I am the only surviving member of this
research team who saw all the phases of this research and I believe it is
important to provide an accurate report, which hopefully will inspire others.
PMID- 28706908
TI - Randomized controlled trials in malignant pleural mesothelioma surgery-mistakes
made and lessons learned.
AB - Randomized surgical trials are of the most difficult to design and recruit,
however, they are the only robust method available to establish a new surgical
procedure. Mesothelioma is a disease with a perceived poor prognosis for which
surgical intervention has relatively high complications and not insignificant
mortality. This review will consider the mesothelioma and radical surgery (MARS)
1 and 2 trials, SAKK 17/04 trial and the EORTC 1205 trial all aimed at assessing
the potential benefit of radical surgery for malignant pleural mesothelioma. In
addition, MesoVATS and MesoTRAP will be explored assessing the value of debulking
surgery for malignant pleural mesothelioma. We also endeavour to identify the
mistakes made and the lessons learned which will inform future randomized
controlled clinical trials in the field of malignant pleural mesothelioma.
Despite the insurmountable problems with randomized controlled clinical trials,
we show that they are possible and continuing with uncontrolled experiments will
perpetuate unproven and potentially harmful operations.
PMID- 28706909
TI - Volumetric assessment in malignant pleural mesothelioma.
AB - Malignant pleural mesothelioma (MPM) is a highly malignant pleural neoplasm with
a dismal prognosis. Multimodality approach including surgery and chemotherapy are
utilized to treat patients with resectable disease. Clinical staging allows for
selection of patients for treatment strategies, but has not been found to be
prognostic and is plagued by high interobserver variability. Tumor volume
measurement on cross-sectional imaging has emerged as a potential quantitative
tool with prognostic significance. This review focuses on volumetric assessment
from cross-sectional imaging (CT, MRI, 18F-FDG PET/CT) and the potential
prognostic benefit and applications.
PMID- 28706910
TI - Malignant pleural mesothelioma: adjuvant therapy with radiation therapy.
AB - It is a challenge to treat malignant pleural mesothelioma with radiation therapy
(RT). For many years, conventional RT was delivered after extrapleural
pneumonectomy (EPP) with acceptable results. However, the benefit of RT has never
been definitively proven. Intensity modulated radiation therapy (IMRT) has been
used, but some of the early experiences revealed fatal toxicity. As experience
has increased, it now appears that RT, particularly with IMRT, is both feasible
and effective.
PMID- 28706911
TI - Malignant pleural mesothelioma: predictors and staging.
AB - Malignant pleural mesothelioma remains a rapidly fatal cancer with few effective
therapies. Unusual anatomic features complicate determination of stage and
prognosis for individual patients. Validation of staging criteria has been
difficult given the rarity of the disease and the fact that only a minority of
patients undergo surgical resection with pathological examination of their
tumors. Thus, additional heuristic factors and algorithms have been taken into
account by clinicians to estimate prognosis and inform discussion of appropriate
management strategies or clinical research protocols with patients.
PMID- 28706912
TI - Diagnosis and prognosis-review of biomarkers for mesothelioma.
AB - Malignant pleural mesothelioma (MPM) is an aggressive disease arising in pleural
cell lining and is associated with asbestos exposure. Today, there is a rising
incidence of MPM reaching 3,000 annual cases nationally, primarily from the large
population occupationally exposed to asbestos between 1940 and 1980. With a
prolonged latency period, presenting clinically 10 to 40 years after exposure,
MPM is often diagnosed in late stages and presents median survival time of less
than 12 months. There is a serious need for improvement in prognostic and
diagnostic tools for MPM. Recent investigation and discovery of various
biomarkers has shown promise, including Osteopontin, Fibulin-3, Soluble
Mesothelin-Related Proteins (SMRP), High Mobility Group Box 1 (HMGB1), micro
RNA's, peripheral blood-based markers, and Slow Off-rate Modified Aptamer
(SOMAmer) proteomic assays. In this review, we explore these current major
biomarkers and their prognostic and diagnostic potential, highlighting the most
recent large studies and developments for each. While progress has been made in
mesothelioma research, many questions remain unanswered. Increased international
cooperation is necessary for improving validity of results for current biomarkers
through repeated investigation and increasing cohort sizes, as well as for the
continued search for new and better markers.
PMID- 28706913
TI - Novel immunotherapy clinical trials in malignant pleural mesothelioma.
AB - In this article, we review ongoing novel clinical trials currently investigating
immunotherapeutic approaches for patients with malignant pleural mesothelioma
(MPM). There is a dearth of effective therapeutic options for patients diagnosed
with MPM and metastatic cancers of the pleura; these diseases have an estimated
annual incidence of 150,000. Modulating the immune microenvironment to promote
antitumor immune responses by systemically and regionally delivered therapeutic
agents is an active area of investigation. We have conducted a review of the
clinical trials database for clinical trials actively recruiting MPM patients. We
focused on novel therapeutic agents administered either systemically or
intrapleurally to modulate the tumor immune microenvironment. Herein, we have
summarized the published results of early phase clinical trials. A total of 43
clinical trials met our inclusion criteria. These trials are investigating
immunologic agents (n=20) and antibody directed therapies (n=23). The regional
intrapleural delivery technique (6 trials) is used to administer chemotherapy
agents (3 of 6 trials) and immunotherapy agents (3 of 6 trials), including
chimeric antigen receptor T cells (1 of 6 trials). Current clinical trials
modulating the MPM immune microenvironment and the combination of these novel
agents with standard of care therapy provide a promising area of investigation
for MPM therapy.
PMID- 28706914
TI - Pleurectomy and decortication.
AB - Pleurectomy and decortication (P/D) improve survival and quality of life in
selected patients with malignant pleural mesothelioma. The operative procedure
was not standardized until recently. The goal of the operation is to perform a
macroscopic complete resection of the tumor. This often involves resection of the
parietal and visceral pleura and invariably a partial or complete resection and
prosthetic reconstruction of ipsilateral hemidiaphragm. We describe our operative
planning and technique as well as outcomes of P/D reported in current literature.
PMID- 28706915
TI - The rationale for neoadjuvant radiation therapy in malignant pleural
mesothelioma: how smart is SMART?
PMID- 28706916
TI - Human microbiome in respiratory diseases.
PMID- 28706917
TI - Insights into study design and statistical analyses in translational microbiome
studies.
AB - Research questions in translational microbiome studies are substantially more
complex than their counterparts in basic science. Robust study designs with
appropriate statistical analysis frameworks are pivotal to the success of these
translational studies. This review considers how study designs can account for
heterogeneous phenotypes by adopting representative sampling schemes for
recruiting the study population and making careful choices about the control
population. Advantages and limitations of 16S profiling and whole-genome
sequencing, the two primary techniques for measuring the microbiome, are
discussed followed by an overview of bioinformatic processing of high-throughput
sequencing data from these measurements. Practical insights into the downstream
statistical analyses including data processing and integration, variable
transformations, and data exploration are provided. The merits of regularization
and ensemble modeling for analyzing microbiome data are discussed along with a
recommendation for selecting modeling approaches based on data-driven simulations
and objective evaluation. The review builds on several recent discussions of
study design issues in microbiome research but with a stronger emphasis on the
downstream and often-ignored aspects of statistical analyses that are crucial for
bridging the gap between basic science and translation.
PMID- 28706918
TI - The respiratory microbiome in idiopathic pulmonary fibrosis.
AB - Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal disease of unknown
cause. Current evidence suggests that it arises in genetically susceptible
individuals as a consequence of an aberrant wound-healing response following
repetitive alveolar injury. Overt respiratory infection and immunosuppression
carry a high mortality, while polymorphisms in genes related to epithelial
integrity and host defence predispose to IPF. Recent advances in sequencing
technologies have allowed the use of molecular microbial technologies to
characterise the respiratory microbiota in patients with IPF. Studies have
suggested that changes in the overall bacterial burden are related to disease
progression and highlighted significant differences between the microbiota in IPF
subjects and healthy controls. Indeed differences in the microbiota between IPF
patients may differentiate those with stable compared to progressive disease. As
our understanding of the IPF microbiome evolves, along with refinement and
advances in sampling and sequencing methodologies we may be able to use microbial
signatures as a biomarker to guide prognostication and even treatment
stratification in this devastating disease.
PMID- 28706919
TI - Microbiome in chronic obstructive pulmonary disease.
AB - The introduction of culture-independent techniques for the microbiological
analysis of respiratory samples has confirmed that the respiratory system hosts a
large number of microorganisms, which include a wide range of bacteria. The
regular exposure to tobacco smoke changes the microbiome in healthy smokers,
first in the oropharynx, increasing the presence of a restricted number of genera
which attain high relative abundance, a pattern that may be considered as
dysbiosis. In chronic obstructive pulmonary disease (COPD), microbiome analyses
of sputum samples have demonstrated an important decline in bacterial diversity,
with a change to a restricted flora with an overrepresentation of the
Proteobacteria phylum, which include most of the bacteria commonly considered as
potentially pathogenic microorganisms, paralleled by a decline in the relative
abundance of microorganisms part of the Firmicutes phylum. In exacerbations,
specific bacteria overrepresented in microbiome analyses and potentially causal
of the acute episode may not be recovered by sputum culture, while colonizing
microorganisms grow easily, in spite that their relative abundance have not
changed from previous stability. This situation has been described in patients
showing chronic colonization by Pseudomonas aeruginosa, who suffer from
exacerbations that in most cases are due to other PPMs, in spite of the
persistence of positive cultures for the colonizing Pseudomonas strains.
Interaction between different microorganisms can be addressed through microbiome
analyses, and functional metagenomics, that describes the genomic potential of
the community, has shown that, in spite that the bronchial microbiome as a whole
may not change significantly, clear changes in carbohydrate metabolism, cancer,
cell growth and death, transport and catabolism pathways often appear during
exacerbations. These functional changes may be important because through them the
resident community as a whole show its power to modify important metabolic
patterns.
PMID- 28706920
TI - Obesity among Sudanese adults with diabetes: a population-based survey.
AB - BACKGROUND: The aim of this study was to determine the prevalence of obesity
among Sudanese individuals with diabetes. METHODS: Demographic and clinical data
from 1,337 individuals with type 2 diabetes were collected using a pretested,
standardized, interviewer administered questionnaire. Subjects were recruited
from three states namely Khartoum, Northern and River Nile States. Anthropometric
measurements including body weight, height and waist circumference were
determined using standardized techniques and calibrated equipment. RESULTS: Total
of 1,337 subjects with type 2 diabetes from Khartoum and North of Sudan were
enrolled in this study and completed the questionnaires; the results showed that
prevalence of obesity among individuals with diabetes was found to be 24.5%, with
a higher rate of obesity in females than males (29.2% versus 18.1%). The
prevalence of central obesity was also higher in women (43.6%) than men (21.8%).
The prevalence of overweight was 39.9%. The overall prevalence of overweight and
obesity was 64.4%. Obesity was associated with age, sex and blood pressure. While
central obesity was associated with an increase in age, female sex and
hypertension. Logistic regression analysis showed that female sex and
hypertension are absolute risk factors for both obesity and central obesity.
CONCLUSIONS: The prevalence of obesity was 24.5% and overweight was 39.9% among
Sudanese individuals with diabetes and more among women than men. Obesity and
central obesity were significantly associated with female sex and hypertension.
PMID- 28706921
TI - Computer tomography guided lung biopsy using interactive breath-hold control: a
randomized study.
AB - BACKGROUND: Interactive breath-hold control (IBC) may improve the accuracy and
decrease the complication rate of computed tomography (CT)-guided lung biopsy,
but this presumption has not been proven in a randomized study. METHODS: Patients
admitted for CT-guided lung biopsy were randomized to biopsy either with (N=201)
or without (N=206) IBC. Biopsy accuracy, procedure time, radiation, and
complications were compared in the two groups. Predictors for pneumothorax were
analyzed. RESULTS: Procedures performed with the use of IBC (N=130) did not show
higher biopsy accuracy (P=0.979) but were associated with a higher risk of
pneumothorax (P=0.022) compared to procedures without the use of IBC (N=171).
Overall, 50% of the biopsies were malignant, 13% were benign, and 33% were
inconclusive (4% missing). Long needle time (P=0.037) and small nodule size
(P=0.001) were predictors of pneumothorax. CONCLUSIONS: The use of IBC for CT
guided lung biopsy was not an advantage for unselected patients in our care,
since it did not improve the biopsy accuracy and the risk of pneumothorax was
increased.
PMID- 28706922
TI - Barriers and enablers to proper diabetic foot care amongst community dwellers in
an Asian population: a qualitative study.
AB - BACKGROUND: Diabetic foot complications are common within Asian populations. They
arise due to poor diabetic control and foot care. In this study, we aimed to
identify the causes for proper and improper diabetic foot care. METHODS: A
qualitative study consisting of key informant interviews with 17 healthcare
professionals, including doctors and various allied health workers, was
conducted. Participants included had at least five years of caring for diabetic
foot patients either in public institutions or private clinics. Data collected
was analyzed via thematic analysis. RESULTS: Diabetic patients were generally
observed to have a mixture of proper and improper information and beliefs which
eventually resulted in the extent of proper foot care. Factors which influenced
the extent of proper and improper state of information and beliefs were
classified into predisposing and precipitating factors. Predisposing factors were
further categorised into modifiable factors (e.g., education level, socioeconomic
status, social support) and non-modifiable factors (e.g., age, presence and
severity of co-morbidities restricting ability to selfcare, past experiences).
Precipitating factors were categorized into patient factors (e.g., degree of
reception of information, presence of psychological barriers), provider factors
(presence and degree of multi-disciplinary approach to care, presence of
administrative inconveniences) and disease factors (presence of diabetic sensory
neuropathy, complexity of disease process). CONCLUSIONS: The extent of proper
foot care amongst diabetic patients is influenced by numerous predisposing and
precipitating factors. Further studies can look at further development of the
described structure as well as quantitatively defining the various components and
factors which make up the described system.
PMID- 28706923
TI - Influence of ABO blood group on sports performance.
AB - BACKGROUND: Despite being a recessive trait, the O blood group is the most
frequent worldwide among the ABO blood types. Since running performance has been
recognized as a major driver of evolutionary advantage in humans, we planned a
study to investigate whether the ABO blood group may have an influence on
endurance running performance in middle-aged recreational athletes. METHODS: The
study population consisted of 52 recreational, middle-aged, Caucasian athletes
(mean age: 49+/-13 years, body mass index, 23.4+/-2.3 kg/m2), regularly engaged
in endurance activity. The athletes participated to a scientific event called
"Run for Science" (R4S), entailing the completion of a 21.1 km (half-marathon)
run under competing conditions. The ABO blood type status of the participants was
provided by the local Service of Transfusion Medicine. RESULTS: In univariate
analysis, running performance was significantly associated with age and weekly
training, but not with body mass index. In multiple linear regression analysis,
age and weekly training remained significantly associated with running
performance. The ABO blood group status was also found to be independently
associated with running time, with O blood type athletes performing better than
those with non-O blood groups. Overall, age, weekly training and O blood group
type explained 62.2% of the total variance of running performance (age, 41.6%;
training regimen, 10.5%; ABO blood group, 10.1%). CONCLUSIONS: The results of our
study show that recreational athletes with O blood group have better endurance
performance compared to those with non-O blood group types. This finding may
provide additional support to the putative evolutionary advantages of carrying
the O blood group.
PMID- 28706924
TI - Abdominal aortic aneurysm: pictorial review of common appearances and
complications.
AB - Abdominal aortic aneurysms (AAAs) are defined as focal dilatations of the
abdominal aorta that are 50% greater than the proximal normal segment or when it
is more than 3 cm in maximum diameter. The early diagnosis and treatment is very
important to prevent catastrophic complications. Due to its ability to assess the
peri-aortic soft tissue and the exact extension of aneurysm, as well as its
excellent vascular opacification and multiplanar reconstruction capabilities,
computed tomography angiography (CTA) has become an integral part of the
evaluation of AAA and has virtually replaced conventional angiography for the
evaluation of AAA. Knowledge of the characteristic imaging features of AAA is
essential for the prompt diagnosis of life-threatening complications. In this
pictorial essay, we will discuss the CTA findings in AAA and its complications
including rupture, infection, aorto-enteric fistula and aorto-caval fistula.
PMID- 28706925
TI - Overcoming preanalytical issues for diagnosing diabetes with fasting plasma
glucose.
PMID- 28706926
TI - Exosomes derived from stimulated monocytes promote endothelial dysfunction and
inflammation in vitro.
PMID- 28706927
TI - Hypertension and cognitive impairment.
PMID- 28706928
TI - Personalised information for improving the uptake of smoking cessation programs.
PMID- 28706929
TI - Diabetes mellitus and multivessel coronary artery disease: an ongoing battle for
an ideal treatment strategy.
PMID- 28706930
TI - Sternal wound management after bilateral internal thoracic artery grafting: a
significant detail.
PMID- 28706931
TI - Extracellular vesicle isolation: present and future.
PMID- 28706932
TI - Atherosclerotic renal artery stenosis.
PMID- 28706933
TI - Atezolizumab in non-small cell lung cancer: the era of precision immuno-oncology.
PMID- 28706934
TI - Hypertensive disorders in pregnancy.
PMID- 28706935
TI - Interview with Prof. Bo Shen: the current status of pouch.
PMID- 28706936
TI - Impact of the host on Toxoplasma stage differentiation.
AB - The unicellular parasite Toxoplasma gondii infects warm-blooded animals and
humans, and it is highly prevalent throughout the world. Infection of
immunocompetent hosts is usually asymptomatic or benign but leads to long-term
parasite persistence mainly within neural and muscular tissues. The transition
from acute primary infection towards chronic toxoplasmosis is accompanied by a
developmental switch from fast replicating and metabolically highly active
tachyzoites to slow replicating and largely dormant bradyzoites within tissue
cysts. Such developmental differentiation is critical for T. gondii in order to
complete its life cycle and for pathogenesis. Herein, we summarize accumulating
evidence indicating a major impact of the host cell physiology on stage
conversion between the tachyzoite and the bradyzoite stage of the parasite.
Withdrawal from cell cycle progression, proinflammatory responses, reduced
availability of nutrients and extracellular adenosine can indeed induce
tachyzoite-to-bradyzoite differentiation and tissue cyst formation. In contrast,
high glycolytic activity as indicated by increased lactate secretion can inhibit
bradyzoite formation. These examples argue for the intriguing possibility that
after dissemination within its host, T. gondii can sense its cellular
microenvironment to initiate the developmental program towards the bradyzoite
stage in distinct cells. This may also explain the predominant localization of T.
gondii in neural and muscular tissues during chronic toxoplasmosis.
PMID- 28706938
TI - Inhibitors of glycosomal protein import provide new leads against
trypanosomiasis.
AB - Vector-borne trypanosomatid parasite infections in tropical and sub-tropical
countries constitute a major threat to humans and livestock. Trypanosoma brucei
parasites are transmitted by tsetse fly and lead to African sleeping sickness in
humans and Nagana in cattle. In Latin American countries, Trypanosoma cruzi
infections spread by triatomine kissing bugs lead to Chagas disease. Various
species of Leishmania transmitted to humans by phlebotomine sandflies manifest in
a spectrum of diseases termed Leishmaniasis. 20 million people are currently
infected with trypanosomatid parasites, leading to over 30,000 deaths annually
and half billion people at risk of the infection. It is estimated that 300,000
Chagas infected people reside in the United States and 100,000 in Europe.
Glycosomes are peroxisome-like organelles found only in trypanosomatids.
Glycolysis occurs in the cytosol in all other organisms, but glycolytic enzymes
and other metabolic pathways are compartmentalized inside glycosomes in
trypanosomatids. Glycosomes are essential for the parasite survival and hence
thought to be an attractive drug target. Our recent study [Dawidowski et al.
Science (2017)] is the first to report small molecule inhibitors of glycosomal
protein import. Using structure-based drug design, we developed small molecule
inhibitors of the Trypanosoma PEX5-PEX14 protein-protein interaction that disrupt
glycosomal protein import and kill the parasites. Oral treatment of T. brucei
infected mice with PEX14 inhibitor significantly reduced the parasite levels with
no adverse effect on mice. The study provides the grounds for further development
of the glycosome inhibitors into clinical candidates and validates the parasite
protein-protein interactions as drug targets.
PMID- 28706939
TI - Chlamydia and mitochondria - an unfragmented relationship.
AB - Presence of pathogens within a eukaryotic cell is apt to generate stress. Such
stress eventually leads to host defense responses, which includes, but is not
limited to, apoptosis induction and subsequent destruction of the host cell and
the pathogen. Obligate intracellular pathogens such as Chlamydia trachomatis are
dependent on the survival of the host cell owing to their unique replication
niche within a membrane-bound inclusion. Furthermore, being energy parasites,
chlamydial development is strictly dependent on the host metabolism. Over the
past decade the role of the small non-coding RNAs called microRNAs (miRNAs) have
come into focus with respect to the regulation of apoptotic signaling, metabolic
homeostasis and bacterial pathogenesis. Effect of Chlamydia infection on the host
miRNA profile was hitherto unknown. In our recent work we demonstrated that
Chlamydia infection induces and requires an upregulation of the host miRNA, miR
30c-5p (miR-30c) to ameliorate infection induced stress on the host mitochondrial
architecture and hinders induction of apoptosis.
PMID- 28706937
TI - The interplay between transcription and mRNA degradation in Saccharomyces
cerevisiae.
AB - The cellular transcriptome is shaped by both the rates of mRNA synthesis in the
nucleus and mRNA degradation in the cytoplasm under a specified condition. The
last decade witnessed an exciting development in the field of post
transcriptional regulation of gene expression which underscored a strong
functional coupling between the transcription and mRNA degradation. The
functional integration is principally mediated by a group of specialized
promoters and transcription factors that govern the stability of their cognate
transcripts by "marking" them with a specific factor termed "coordinator." The
"mark" carried by the message is later decoded in the cytoplasm which involves
the stimulation of one or more mRNA-decay factors, either directly by the
"coordinator" itself or in an indirect manner. Activation of the decay factor(s),
in turn, leads to the alteration of the stability of the marked message in a
selective fashion. Thus, the integration between mRNA synthesis and decay plays a
potentially significant role to shape appropriate gene expression profiles during
cell cycle progression, cell division, cellular differentiation and
proliferation, stress, immune and inflammatory responses, and may enhance the
rate of biological evolution.
PMID- 28706940
TI - Recent Advances in High Throughput Sequencing Analysis.
PMID- 28706941
TI - Application of Response Surface Methodology to Study the Effects of Brisket Fat,
Soy Protein Isolate, and Cornstarch on Nutritional and Textural Properties of
Rabbit Sausages.
AB - The effects of brisket fat, soy protein isolate, and cornstarch on chemical and
textural properties of rabbit sausages were studied using surface response
methodology. Sausage samples were prepared using a five-level three-variable
Central Composite Rotatable Design with 16 combinations, including two replicates
of the center point, carried out in random order. The level of brisket fat (BF),
soy protein isolate (SPI), and cornstarch (CS) in the sausage formulation ranged
within 8.3-16.7%, 0.7-2.3%, and 1.3-4.7%, respectively. Increasing BF decreased
moisture and ash contents but increased protein and fat contents of the sausages
(p < 0.05). Increasing SPI increased moisture content but decreased ash and
carbohydrate contents of the sausages (p < 0.05). Increasing CS increased
carbohydrate content (p < 0.05). Increasing BF increased hardness, adhesiveness,
cohesiveness, and chewiness but decreased springiness (p < 0.05). SPI addition
increased springiness but decreased adhesiveness, cohesiveness, and chewiness (p
< 0.05). In conclusion, varying the levels of BF and SPI had a more significant
effect on chemical and textural properties of rabbit sausages than CS.
PMID- 28706942
TI - Evaluation of the Sealing Ability of Three Obturation Techniques Using a Glucose
Leakage Test.
AB - The aim of this study was to evaluate the sealing ability of three different
canal filling techniques. Sixty-four roots of extracted human maxillary anterior
teeth were prepared using ProTaper(r) rotary instruments. The specimens were then
randomly divided into 3 experimental groups (n = 16) and 2 control groups (n =
8). The root canals were filled using cold lateral compaction (CLC group),
continuous wave condensation technique using the Elements Obturation Unit(r) (EOU
group), and ProTaper obturators (PT group). For the negative control group, 8
roots were filled using lateral compaction as in the CLC group, and the teeth
were covered twice with a layer of nail varnish (NCG group). Another 8 roots were
filled using lateral compaction, but without sealer, and these were used as the
positive control (PCG group). A glucose leakage model was used for quantitative
evaluation of microleakage for 24 hours and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11,
and 12 weeks. No significant difference in the cumulative amount of leakage was
found between the three experimental groups at all observation times. The lateral
condensation of cold gutta-percha can guarantee a similar seal of canal fillings
as can be achieved by using thermal methods, in the round canals.
PMID- 28706943
TI - Correlation of IOP with Corneal Acoustic Impedance in Porcine Eye Model.
AB - PURPOSE: The aim of this study is to correlate the intraocular pressure (IOP)
change with the acoustic impedance of the cornea, in order to propose a
noncontact and noninvasive method for IOP monitoring. METHODS AND MATERIALS: A
highly focused transducer (frequency 47-MHz; bandwidth 62%) was made to measure
the echo from the anterior and posterior surfaces of intact porcine eyes,
respectively. A multilayered transmission and reflection model was used to
calculate the acoustic impedance. The linear relationship between acoustic
impedance and intraocular pressure was analyzed by statistical method. RESULT:
During pressure elevation from 10 mm Hg to 50 mm Hg, the mean acoustic impedance
of the posterior cornea increased from 1.5393 to 1.5698 MRayl, which showed a
strong linear correlation (R = 0.9849; P = 0.0022). Meanwhile, the mean value of
the anterior cornea increased from 1.5399 to 1.5519 MRayl, and a less significant
correlation was observed (R = 0.7378; P = 0.0025). CONCLUSION: This study
revealed a linear correlation between intraocular pressure and acoustic impedance
of the cornea, thus demonstrating a potentially important method to noninvasively
measure the intraocular pressure in vivo.
PMID- 28706944
TI - Schisandrin B Prevents Hind Limb from Ischemia-Reperfusion-Induced Oxidative
Stress and Inflammation via MAPK/NF-kappaB Pathways in Rats.
AB - Schisandrin B (ScB), isolated from Schisandra chinensis (S. chinensis), is a
traditional Chinese medicine with proven cardioprotective and neuroprotective
effects. However, it is unclear whether ScB also has beneficial effects on rat
hind limb ischemia/reperfusion (I/R) injury model. In this study, ScB (20 mg/kg,
40 mg/kg, and 80 mg/kg) was administered via oral gavage once daily for 5 days
before the surgery. After 6 h ischemia and 24 h reperfusion of left hind limb,
ScB reduced I/R induced histological changes and edema. ScB also suppressed the
oxidative stress through decreasing MDA level and increasing SOD activity.
Moreover, above changes were associated with downregulated TNF-alpha mRNA
expression and reduced level of IL-1beta in plasma. Meanwhile, ScB treatment
downregulated activation of p38MAPK, ERK1/2, and NF-kappaB in ischemic skeletal
muscle. These results demonstrate that ScB treatment could prevent hind limb I/R
skeletal muscle injury possibly by attenuating oxidative stress and inflammation
via p38MAPK, ERK1/2, and NF-kappaB pathways.
PMID- 28706945
TI - Measuring Family Members' Satisfaction with End-of-Life Care in Long-Term Care:
Adaptation of the CANHELP Lite Questionnaire.
AB - RATIONALE: Improving end-of-life care (EOLC) in long-term care (LTC) homes
requires quality measurement tools that assess families' satisfaction with care.
This research adapted and pilot-tested an EOLC satisfaction measure (Canadian
Health Care Evaluation Project (CANHELP) Lite Questionnaire) for use in LTC to
measure families' perceptions of the EOLC experience and to be self-administered.
METHODS AND RESULTS: Phase 1. A literature review identified key domains of
satisfaction with EOLC in LTC, and original survey items were assessed for
inclusiveness and relevance. Items were modified, and one item was added. PHASE
2: The revised questionnaire was administered to 118 LTC family members and
cognitive interviews were conducted. Further modifications were made including
reformatting to be self-administered. PHASE 3: The new instrument was pilot
tested with 134 family members. Importance ratings indicated good content and
face validity. Cronbach's alpha coefficients (range: .88-.94) indicated internal
consistency. CONCLUSION: This research adapted and pilot-tested the CANHELP for
use in LTC. This paper introduces the new, valid, internally consistent, self
administered tool (CANHELP Lite Family Caregiver LTC) that can be used to measure
families' perceptions of and satisfaction with EOLC. Future research should
further validate the instrument and test its usefulness for quality improvement
and care planning.
PMID- 28706946
TI - Chronic Kidney Disease-Mineral and Bone Disorder.
PMID- 28706947
TI - p21-Activated Kinase 4 Promotes Intimal Hyperplasia and Vascular Smooth Muscle
Cells Proliferation during Superficial Femoral Artery Restenosis after
Angioplasty.
AB - The aim of this study is to explore the function of p21-activated kinase 4 (PAK4)
in intimal hyperplasia (IH) and vascular smooth muscle cells (VSMCs)
proliferation. We choose vascular samples from patients undergoing angioplasty in
superficial femoral artery (SFA) as the experimental group and vascular samples
from donors without clinical SFA restenosis as the control group, respectively.
We draw from the results that both levels of mRNA and protein of PAK4 in the
experimental group increased dramatically compared with the control group. IH
arose from angioplasty of SFA. Moreover, overexpression of PAK4 dramatically
contributed to cell proliferation of VSMCs and promoted cell cycle progression
from G0/G1 phase (71.12 +/- 0.69% versus 58.77 +/- 0.77%, P < 0.001) into S phase
(23.99 +/- 0.21% versus 31.35 +/- 0.33%, P < 0.001). Besides, PAK4 downregulated
the level of p21 and enhanced the activity of Akt as well. And we conclude that
PAK4 acts as a regulator of cell cycle progression of VSMC by mediating Akt
signaling and controlling p21 levels, which further modulate IH and VSMCs'
proliferation.
PMID- 28706948
TI - What Kind of Doctor Do You Want to Be? Geriatric Medicine Podcast as a Career
Planning Resource.
AB - INTRODUCTION: For optimal direction in career paths and postgraduate training,
students can benefit from information to guide them through options. Using
geriatric medicine as a template, the goal was to develop a multimedia podcast
resource that can give a clearer picture of what a specialty entails. METHODS:
The project included a survey of existing resources and needs assessment of
medical students at the University of Ottawa, Canada. This survey assessed
students' knowledge of geriatrics and interest in the field and explored what
they foresee as being important to be informed on when considering application to
programs. Based on this, interview questions and content were developed for a
podcast which was then evaluated. RESULTS: Interviews were conducted with
physicians and residents nationwide. Relevant resources and links were added to
the podcast. Evaluation demonstrated improved student understanding and interest
in geriatric medicine as a career. Point-by-point format for a template on how to
develop similar podcasts was developed to assist other specialties looking to
develop similar information. CONCLUSIONS: As no such framework currently exists,
results of this project can serve as a template for other postgraduate programs
in developing a multimedia resource for informing prospective trainees.
PMID- 28706949
TI - Genetic Variant of Kalirin Gene Is Associated with Ischemic Stroke in a Chinese
Han Population.
AB - INTRODUCTION: Ischemic stroke is a complex disorder resulting from the interplay
of genetic and environmental factors. Previous studies showed that kalirin gene
variations were associated with cardiovascular disease. However, the association
between this gene and ischemic stroke was unknown. We performed this study to
confirm if kalirin gene variation was associated with ischemic stroke. METHODS:
We enrolled 385 ischemic stroke patients and 362 controls from China. Three SNPs
of kalirin gene were genotyped by means of ligase detection reaction-PCR method.
Data was processed with SPSS and SHEsis platform. RESULTS: SNP rs7620580
(dominant model: OR = 1.590, p = 0.002 and adjusted OR = 1.662, p = 0.014;
additive model: OR = 1.490, p = 0.002 and adjusted OR = 1.636, p = 0.005;
recessive model: OR = 2.686, p = 0.039) and SNP rs1708303 (dominant model: OR =
1.523, p = 0.007 and adjusted OR = 1.604, p = 0.028; additive model: OR = 1.438,
p = 0.01 and adjusted OR = 1.476, p = 0.039) were associated with ischemic
stroke. The GG genotype and G allele of SNP rs7620580 were associated with a risk
for ischemic stroke with an adjusted OR of 3.195 and an OR of 1.446,
respectively. Haplotype analysis revealed that A-T-G,G-T-A, and A-T-A haplotypes
were associated with ischemic stroke. CONCLUSIONS: Our results provide evidence
that kalirin gene variations were associated with ischemic stroke in the Chinese
Han population.
PMID- 28706950
TI - Effects of Cobalt Chloride, a Hypoxia-Mimetic Agent, on Autophagy and Atrophy in
Skeletal C2C12 Myotubes.
AB - BACKGROUND: Hypoxia-induced autophagy and muscle wasting occur in several
environmental and pathological conditions. However, the molecular mechanisms
underlying the effects of the hypoxia-mimetic agent CoCl2 on autophagy and muscle
atrophy are still unclear. METHODS: C2C12 myotubes were exposed to increasing
concentrations of CoCl2 for 24 hours. Quantitative RT-PCR, Western blotting, and
transmission electron microscopy were performed to confirm autophagy occurs.
Autophagy proteins were measured to understand the molecule mechanisms. We also
inhibited hypoxic autophagy and examined the changes in myogenin expression,
myotubes formation, and apoptosis. RESULTS: Our results showed that CoCl2
mimicked hypoxia upregulated the expression of the autophagy-related proteins
LC3, HIF-1alpha, BNIP3, p-AMPKalpha, and beclin-1, whereas p62 and p-mTOR were
downregulated. In addition, the autophagosome could be observed after CoCl2
induction. The expression of the autophagy-related E3 ligase parkin and the
muscle-specific ubiquitin ligase atrogin-1 was increased by CoCl2. Inhibition of
autophagy by 3MA increased myogenin expression and promoted myotubes formation
and the percentage of cell death was decreased. CONCLUSIONS: Our results
confirmed that CoCl2-mimicked hypoxia induced autophagy via the HIF
1alpha/BNIP3/beclin-1 and AMPK/mTOR pathways. Our results also revealed an
important link between autophagy and muscle atrophy under hypoxia, which may help
to develop new therapeutic strategies for muscle diseases.
PMID- 28706951
TI - Effectiveness of Different Pain Control Methods in Patients with Knee
Osteoarthritis after Knee Arthroplasty.
AB - The number of patients with knee osteoarthritis has increased in tandem with
population aging. Consequently, the number of knee arthroplasties has also risen.
The postoperative pain is the biggest challenge faced by patients soon after knee
arthroplasty; therefore, this study is among different methods for post-knee
arthroplasty pain control. A prospective longitudinal research design was
employed; 177 adult patients who proposed for primary knee arthroplasty were
enrolled and recruited. The patients were divided into conventional Group 1 (n =
120) and patient-controlled analgesia (PCA) Group 2 (n = 57) according to the
treatment methods they received. All patients experience the highest pain level
on the day of their surgery; women complained of higher pain levels than men did,
while the PCA group had lower postoperative pain. Meanwhile, patients with
general anesthesia experienced more pain than those with spinal anesthesia in
postoperative period. Patients with a higher postoperative pain index have a
smaller optimal knee flexion angle. The PCA group had lower postoperative pain;
all patients experienced the highest pain level on the day of their surgery. The
results of this study could serve as a reference for nurses where PCA ensures a
better postoperative pain control and therefore facilitates recovery and improves
the quality of nursing.
PMID- 28706952
TI - Development of an Economical Method to Reduce the Extractable Latex Protein
Levels in Finished Dipped Rubber Products.
AB - Natural rubber latex (NRL) allergy is caused by the extractable latex proteins in
dipped rubber products. It is a major concern for the consumers who are sensitive
to the allergenic extractable proteins (EP) in products such as NRL gloves.
Objective of this research was to develop an economical method to reduce the EP
in finished dipped NRL products. In order to reduce the EP levels, two natural
proteases, bromelain from pineapple and papain from papaya, were extracted and
partially purified using (NH4)2SO4. According to the newly developed method,
different glove samples were treated with a 5% solution of each partially
purified enzyme, for 2 hours at 60 degrees C. Residual amounts of in treated
samples were quantified using the modified Lowry assay (ASTM D5712-10). Bromelain
displayed a 54 (+/-11)% reduction of the EP from the dipped rubber products,
whereas it was 58 (+/-8)% with papain. These results clearly indicate that the
selected natural proteases, bromelain, and papain contribute significantly
towards the reduction of the total EP in finished NRL products. Application of
bromelain enzyme for the aforementioned purpose has not been reported up to date,
whereas papain has been used to treat raw NRL towards reducing the EP.
PMID- 28706953
TI - Differentially Expressed MicroRNAs in the Development of Early Diabetic
Retinopathy.
AB - The pathological mechanisms of diabetic retinopathy (DR), a leading cause of
blindness in adults with diabetes mellitus, remain incompletely understood.
Because microRNAs (miRNAs) represent effective DR therapeutic targets, we
identified aberrantly expressed miRNAs associated with cellular dysfunction in
early DR and detected their potential targets. We exposed human retinal
endothelial cells (HRECs) and a cell line of retinal pigment epithelial (RPE)
cells to high glucose (25 mmol/L, 1-7 days) to mimic DR progression and used
streptozotocin-injected rats (4-8 weeks) for an in vivo diabetes model. HREC/RPE
viability decreased after 24 h incubation and diminished further over 6 days, and
Hoechst staining revealed hyperglycemia-induced HREC/RPE apoptosis. Although miR
124/-125b expression decreased with DR progression in vitro and in vivo, miR
135b/-199a levels decreased in retinal cells under hyperglycemia exposure, but
increased in diabetic retinas. Moreover, miR-145/-146a expression decreased
gradually in high-glucose-treated HRECs, but increased in hyperglycemia-exposed
RPE cells and in diabetic rats. Our findings suggested that aberrant miRNA
expression could be involved in hyperglycemia-induced retinal-cell dysfunction,
and the identified miRNAs might vary in different retinal layers, with expression
changes associated with DR development. Therefore, miRNA modulation and the
targeting of miRNA effects on transcription factors could represent novel and
effective DR-treatment strategies.
PMID- 28706954
TI - Association between the Time of Length since Smoking Cessation and Insulin
Resistance in Asymptomatic Korean Male Ex-Smokers.
AB - AIM: Smoking is a major risk factor for diabetes mellitus, mainly due to
decreased insulin secretion and increased insulin resistance. However, there has
been little research on the effects of smoking cessation period on changes in
insulin resistance. In this study, we investigated the relationships between the
length of time since smoking cessation period and insulin resistance in
asymptomatic Korean male ex-smokers. METHODS: A total of 851 male adults were
included in this study. We considered several factors that can affect insulin
resistance, and through multiple linear regression analysis, we assessed the
effect the length of time since smoking cessation on insulin resistance in ex
smokers. Insulin resistance was represented as the insulin resistance index
estimated by homeostasis model assessment. RESULTS: HOMA-IR values showed a
statistically significant negative correlation with the length of time since
smoking cessation (p = 0.009) in ex-smokers. After performing multiple linear
regression analysis using factors that could potentially influence insulin
resistance, we found that waist circumference (p = 0.026) and the length of time
since smoking cessation (p = 0.039) were independent predictors of HOMA-IR in
asymptomatic male ex-smokers. CONCLUSION: The longer the smoking cessation
period, the more the insulin resistance tended to decrease in asymptomatic Korean
male ex-smokers.
PMID- 28706955
TI - Effect of Sugar versus Mixed Breakfast on Metabolic and Neurofunctional Responses
in Healthy Individuals.
AB - We investigated the effects of glucose and diverse breakfasts on glucose
increment and ghrelin suppression and cognitive processing of sensory information
assessed by frontal P300 evoked potentials. In a randomized crossover design, 12
healthy individuals (6M/6F; BMI 22.2 +/- 0.4 kg/m2; 27 +/- 1.3 years, mean +/-
SEM) underwent 50 g OGTT (A) and 3 breakfasts (B1: milk and cereals; B2: milk,
apple, and chocolate cream-filled sponge cake; B3: milk, apple, bread, and
hazelnut chocolate cream) to assess plasma glucose-, insulin-, and ghrelin
excursions. An electroencephalography was performed before and 100 min after
consumption of each load to measure the latency of frontal P300 evoked potentials
as index of cognitive performance. Breakfasts B1 and B2 exhibited significantly
lower glycemic and insulinemic responses as compared to A. Breakfast B3 exhibited
significantly lower glycemic, but not insulinemic response, as compared to A.
Final plasma ghrelin inhibition was more pronounced, albeit not significantly, in
all breakfasts with respect to A. P300 latency tended to decrease following each
of the three breakfasts, but B3 was the only breakfast capable to elicit a
statistically significant reduction in P300 latency with respect to A (p < 0.01),
suggesting ameliorated cognitive performance. Such amelioration was correlated
with the 2-hour final inhibition of plasma ghrelin concentration (r = 0.61, p =
0.01).
PMID- 28706956
TI - Ethyl Caffeate Ameliorates Collagen-Induced Arthritis by Suppressing Th1 Immune
Response.
AB - The present study was designed to assess the antiarthritic potential of ECF in
collagen-induced arthritis (CIA) and explore its underlying mechanism. Methods.
In vitro, lymphocyte proliferation assay was measured by CCK-8 kit. In vivo, the
therapeutic potential of ECF on CIA was investigated; surface marker, Treg cell,
and intracellular cytokines (IL-17A and IFN-gamma) were detected by flow
cytometry. Th1 cell differentiation assay was performed, and mRNA expression in
interferon-gamma-related signaling was examined by q-PCR analysis. Results. In
vitro, ECF markedly inhibited the proliferation of splenocytes in response to
ConA and anti-CD3. In vivo, ECF treatment reduced the severity of CIA, inhibited
IFN-gamma and IL-6 secretion, and decreased the proportion of CD11b+Gr-1+ splenic
neutrophil. Meanwhile, ECF treatment significantly inhibited the IFN-gamma
expression in CD4+T cell without obviously influencing the development of Th17
cells and T regulatory cells. In vitro, ECF suppressed the differentiation of
naive CD4+ T cells into Th1. Furthermore, ECF intensely blocked the
transcriptional expression in interferon-gamma-related signaling, including IFN
gamma, T-bet, STAT1, and STAT4. Conclusion. Our results indicated that ECF
exerted antiarthritic potential in collagen-induced arthritis by suppressing Th1
immune response and interferon-gamma-related signaling.
PMID- 28706958
TI - Toll-like receptor 2-mediated NF-kappa B pathway activation in ocular surface
epithelial cells.
AB - BACKGROUND: Gram-positive bacteria stimulate Toll-like receptor (TLR) 2 and then
activate the pro-inflammatory nuclear factor-kappa B (NF-kappaB) pathway. As the
human ocular surface is heavily colonised by gram-positive cocci bacteria, a
balance of activation/repression of NF-kappaB target genes is essential to avoid
uncontrolled infection or autoimmune-related inflammation. It is advantageous to
test NF-kappaB targeting molecules in an ocular surface culture system that
allows assessment of temporal NF-kappaB activation in a longitudinal fashion
without destruction of cells. Such initial testing under standardised conditions
should reduce the number of molecules that progress to further evaluation in
animal models. This study aims to establish an in-vitro cell culture system to
assess NF-kappaB activation in the context of ocular surface cells. METHODS: NF
kappaB activity was evaluated through a secretory alkaline phosphatase reporter
assay (SEAP). Immunoblots and immunofluorescence were used to examine
IkappaBalpha phosphorylation and p65/p50 nuclear localization. Monocyte
chemoattractant protein-1 (MCP-1) transcripts were evaluated by real time PCR and
protein levels were measured by ELISA. RESULTS: NF-kappaB activity in HCE-T cells
treated with TLR2 activator Pam3CSK4 was higher than control cells at both 6 and
24 h. Pam3CSK4-stimulated NF-kappaB activation was inhibited by IkappaK
inhibitors, Wedelolactone and BMS-345541. In Pam3CSK4 treated cells, active NF
kappaB subunits p50 and p65 increased in cell nuclear fractions as early as 1.5
h. Although the level of total IkappaB-alpha remained constant, phospho-IkappaB
alpha increased with treatment over time. In the culture media of Pam3CSK4
stimulated cells, MCP-1 protein level was increased, which was suppressed in the
presence of IkappaK inhibitors. CONCLUSION: NF-kappaB pathway can be activated by
the TLR2 ligand and inhibited by IkappaK inhibitors in the ocular surface cell
culture system. This cell culture system may be used to evaluate TLR-related
innate defences in ocular surface diseases.
PMID- 28706957
TI - The Controversial C5a Receptor C5aR2: Its Role in Health and Disease.
AB - After the discovery of the C5a receptor C5aR1, C5aR2 is the second receptor found
to bind C5a and its des-arginine form. As a heptahelical G protein-coupled
receptor but devoid of the intracellular Galpha signal, C5aR2 is special and
confusing. Ramifications and controversies about C5aR2 are under debate since its
identification, from putative ligands and cellular localization to intracellular
signals and pathological roles in inflammation and immunity. The ruleless and
even conflicting pro- or anti-inflammatory role of C5aR2 in animal models of
diverse diseases makes one bewildered. This review summarizes reports on C5aR2,
tries to clear up available evidence on these four controversial aspects, and
delineates C5aR2 function(s). It also summarizes available toolboxes for C5aR2
study.
PMID- 28706959
TI - Sensitivity, specificity and predictive values of anterior chamber tap in cases
of bacterial endophthalmitis.
AB - BACKGROUND: To assess the sensitivity, specificity, positive predictive value and
negative predictive value of anterior chamber tap for the diagnosis of bacterial
endophthalmitis on a population with high prevalence. METHODS: Retrospective,
single centre, case series study. We reviewed all medical records with clinical
diagnosis of bacterial endophthalmitis in our hospital from January 1st, 2000 to
December 31st 2014. From each record, we documented general demographic data,
best corrected visual acuity and vitreous and aqueous tap microbiological
results. All cases were further divided according to the endophthalmitis
aetiology to perform individual calculations of sensitivity, specificity,
positive predictive value, negative predictive value, accuracy and prevalence. We
used the results of the vitreous tap as the gold standard for diagnosis of
bacterial endophthalmitis. We excluded those records in which the aqueous and
vitreous samples were not taken simultaneously or had an incomplete
microbiological report. Significance were assessed with chi squared statistics,
with an alpha value of 0.05 for statistical significance. RESULTS: A total of 190
cases fulfilled the inclusion/exclusion criteria. Positive culture rate from
vitreous samples was 64.74%. Positive culture rate from aqueous sample was
32.11%. Bacteria isolated from aqueous samples matched those isolated from
vitreous samples 78.68% of the time. The overall sensitivity was 38.21%,
specificity: 75.51%, positive predictive value: 79.66%, negative predictive
value: 32.74% (p = 0.08). Subgroup analysis showed that anterior chamber taps in
cases of post-surgical endophthalmitis had a moderate to low sensitivity
(37.73%), high specificity (93%) and high positive predictive value (95%) (p <
0.04). CONCLUSION: The sensitivity and specificity of anterior chamber tap are
low and should not be used for critical therapeutic decisions in patients with
suspected bacterial endophthalmitis. In cases of post-surgical endophthalmitis,
the result of an anterior chamber tap could be used for therapeutic guidance, but
only in conjunction with clinical presentation and in the absence of a better
method for diagnosis.
PMID- 28706960
TI - Acute Interstitial Nephritis Associated with Sofosbuvir and Daclatasvir.
AB - Although new heptatis C virus treatments have increased efficacy and improved
safety profiles, they also come with risk. We describe a 66-year-old white man
with Child-Pugh A cirrhosis secondary to heptatis C virus genotype 3, who
suffered from an acute kidney injury after treatment with sofosbuvir and
daclatasvir. Kidney biopsy demonstrated evidence of acute tubular interstitial
nephritis consistent with a drug reaction. A trial of steroid therapy was
effective, and his creatinine continues to improve significantly. Our case is the
first report in the literature that highlights potentially serious interstitial
nephritis associated with sofosbuvir and daclatasvir use.
PMID- 28706961
TI - Multiple Myeloma Presenting as Acute Liver Failure.
AB - Liver failure is rarely caused by multiple myeloma (MM). We present an unusual
case of MM initially presenting as acute liver injury. A 79-year-old man with new
onset fatigue, decreased appetite, and no history of liver disease was found to
have evidence of hepatic decompensation. Liver biopsy demonstrated diffuse plasma
cell infiltration, and MM was confirmed with bone marrow biopsy. Chemotherapy was
initiated, but the patient decompensated and died due to respiratory failure. MM
should be considered on the differential for acute decompensated liver disease.
Hepatic involvement of MM at presentation is a poor prognostic indicator, and
prompt initiation of treatment can be life-saving.
PMID- 28706962
TI - Posttransplant Lymphoproliferative Disorder of the Small Bowel as an Unexpected
Cause of Iron Deficiency Anemia Decades after Heart Transplantation.
AB - Although rare, gastrointestinal posttransplant lymphoproliferative disorder
(PTLD) can lead to abdominal pain or gastrointestinal bleeding in patients with a
history of solid-organ transplantation. We describe a case of isolated
gastrointestinal PTLD in a patient who presented with acute on chronic iron
deficiency anemia 26 years after heart transplant. A comprehensive endoscopic
evaluation with video capsule endoscopy and small bowel enteroscopy revealed a
large cratered ulceration in the small bowel with abnormal mucosal changes, which
led to the diagnosis of PTLD.
PMID- 28706963
TI - CRISPR/Cas9 Editing of the Bacillus subtilis Genome.
AB - A fundamental procedure for most modern biologists is the genetic manipulation of
the organism under study. Although many different methods for editing bacterial
genomes have been used in laboratories for decades, the adaptation of CRISPR/Cas9
technology to bacterial genetics has allowed researchers to manipulate bacterial
genomes with unparalleled facility. CRISPR/Cas9 has allowed for genome edits to
be more precise, while also increasing the efficiency of transferring mutations
into a variety of genetic backgrounds. As a result, the advantages are realized
in tractable organisms and organisms that have been refractory to genetic
manipulation. Here, we describe our method for editing the genome of the
bacterium Bacillus subtilis. Our method is highly efficient, resulting in
precise, markerless mutations. Further, after generating the editing plasmid, the
mutation can be quickly introduced into several genetic backgrounds, greatly
increasing the speed with which genetic analyses may be performed.
PMID- 28706964
TI - Residual stress distribution analysis of heat treated APS TBC using image based
modelling.
AB - We carried out a residual stress distribution analysis in a APS TBC throughout
the depth of the coatings. The samples were heat treated at 1150 degrees C for
190 h and the data analysis used image based modelling based on the real 3D
images measured by Computed Tomography (CT). The stress distribution in several
2D slices from the 3D model is included in this paper as well as the stress
distribution along several paths shown on the slices. Our analysis can explain
the occurrence of the "jump" features near the interface between the top coat and
the bond coat. These features in the residual stress distribution trend were
measured (as a function of depth) by high-energy synchrotron XRD (as shown in our
related research article entitled 'Understanding the Residual Stress Distribution
through the Thickness of Atmosphere Plasma Sprayed (APS) Thermal Barrier Coatings
(TBCs) by high energy Synchrotron XRD; Digital Image Correlation (DIC) and Image
Based Modelling') (Li et al., 2017) [1].
PMID- 28706965
TI - Experiments on deformation behaviour of functionally graded NiTi structures.
AB - Functionally graded NiTi structures benefit from the combination of the smart
properties of NiTi and those of functionally graded structures. This article
provides experimental data for thermomechanical deformation behaviour of
microstructurally graded, compositionally graded and geometrically graded NiTi
alloy components, related to the research article entitled "Functionally graded
shape memory alloys: design, fabrication and experimental evaluation" (Shariat et
al., 2017) [1]. Stress-strain variation of microstructurally graded NiTi wires is
presented at different heat treatment conditions and testing temperatures. The
complex 4-way shape memory behaviour of a compositionally graded NiTi strip
during one complete thermal cycle is demonstrated. The effects of geometrical
design on pseudoelastic behaviour of geometrically graded NiTi plates over
tensile loading cycles are presented on the stress-strain diagrams.
PMID- 28706966
TI - Data on the fate of MACS(r) MicroBeads intramyocardially co-injected with stem
cell products.
AB - The data presented in this article are related to the research article
"Intramyocardial Fate and Effect of Iron Nanoparticles co-injected with MACS(r)
purified Stem Cell Products" (Muller et al., 2017) [1]. This article complements
the cellular localization of superparamagnetic iron dextran particles (MACS(r)
MicroBeads) used for magnetic activated cell sorting (MACS(r)). Data evaluate the
time-dependent detachment of these nanoparticles from CD133+ haematopoietic stem
cells (HSCs) and CD271+ mesenchymal stem cells (MSCs). Furthermore, the influence
of these stem cells as well as of nanoparticles on cardiac remodeling processes
after myocardial infarction (MI) was investigated.
PMID- 28706967
TI - Geospatial analysis of dissolved nutrients dataset in the surface water of
Karayar reservoir, Southern India.
AB - Spatial dataset representing the nutrient distribution in Karayar reservoir
during pre and post-monsoon season is presented. Random sampling method was used
for data collection and the sample location were fixed using a handheld global
positioning system (Garmin GPSMAP-76). The nutrients were estimated using the
standard techniques as described in the American Public Health Association (APHA)
manual. Physical parameters were estimated using a Hanna portable multi water
quality probe (HI-9828, USA). The spatial distribution of physical and nutrient
content in surface water is carried out using an inverse distance weighted
technique.
PMID- 28706968
TI - BRCA1 reversion mutation acquired after treatment identified by liquid biopsy.
AB - *Secondary, reversion mutations in BRCA genes can restore protein
function.*Reversion mutations can underlie resistance to therapies such as PARP
inhibitors.*Reversion mutations arise during the course of treatment.
PMID- 28706969
TI - Quantitative analysis of immune cell subset infiltration of supraspinatus muscle
after severe rotator cuff injury.
AB - Rotator cuff tears cause muscle degeneration that is characterized by myofiber
atrophy, fatty infiltration, and fibrosis and is minimally responsive to current
treatment options. The underlying pathogenesis of rotator cuff muscle
degeneration remains to be elucidated, and increasing evidence implicates immune
cell infiltration as a significant factor. Because immune cells are comprised of
highly heterogeneous subpopulations that exert divergent effects on injured
tissue, understanding trafficking and accumulation of immune subpopulations may
hold the key to more effective therapies. The present study quantifies
subpopulations of immune cells infiltrating the murine supraspinatus muscle after
severe rotator cuff injury that includes tenotomy and denervation. Rotator cuff
injury stimulates dramatic infiltration of mononuclear phagocytes, enriches
mononuclear phagocytes in non-classical subpopulations, and enriches T
lymphocytes in TH and Treg subpopulations. The combination of tenotomy plus
denervation significantly increases mononuclear phagocyte infiltration, enriches
macrophages in the non-classical subpopulation, and decreases T lymphocyte
enrichment in TH cells compared to tenotomy alone. Depletion of circulating
monocytes via liposomal clodronate accelerates supraspinatus atrophy after
tenotomy and denervation. The study may aid rational design of immunologically
smart therapies that harness immune cells to enhance outcomes after rotator cuff
tears.
PMID- 28706970
TI - Reversibility of Frailty After Bridge-to-Transplant Ventricular Assist Device
Implantation or Heart Transplantation.
AB - BACKGROUND: We recently reported that frailty is independently predictive of
increased mortality in patients with advanced heart failure referred for heart
transplantation (HTx). The aim of this study was to assess the impact of frailty
on short-term outcomes after bridge-to-transplant ventricular assist device (BTT
VAD) implantation and/or HTx and to determine if frailty is reversible after
these procedures. METHODS: Between August 2013 and August 2016, 100 of 126
consecutive patients underwent frailty assessment using Fried's Frailty Phenotype
before surgical intervention: 40 (21 nonfrail, 19 frail) BTT-VAD and 77 (60
nonfrail, 17 frail) HTx-including 17 of the 40 BTT-VAD supported patients.
Postprocedural survival, intubation time, intensive care unit, and hospital
length of stay were compared between frail and nonfrail groups. Twenty-six frail
patients were reassessed at 2 months or longer postintervention. RESULTS: Frail
patients had lower survival (63 +/- 10% vs 94 +/- 3% at 1 year, P = 0.012) and
experienced significantly longer intensive care unit (11 vs 5 days, P = 0.002)
and hospital (49 vs 25 days, P = 0.003) length of stay after surgical
intervention compared with nonfrail patients. Twelve of 13 frail patients
improved their frailty score after VAD (4.0 +/- 0.8 to 1.4 +/- 1.1, P < 0.001)
and 12 of 13 frail patients improved their frailty score after HTx (3.2 +/- 0.4
to 0.9 +/- 0.9, P < 0.001). Handgrip strength and depression improved
postintervention. Only a slight improvement in cognitive function was seen
postintervention. CONCLUSIONS: Frail patients with advanced heart failure
experience increased mortality and morbidity after surgical intervention with BTT
VAD or HTx. Among those who survive frailty is partly or completely reversible
underscoring the importance of considering this factor as a dynamic not fixed
entity.
PMID- 28706971
TI - A Donor Age-Based and Graft Volume-Based Analysis for Living Donor Liver
Transplantation in Elderly Recipients.
AB - BACKGROUND: Given the expected increase in the number of elderly recipients,
details regarding how clinical factors influence the outcome in living donor
liver transplantation (LDLT) for the elderly remain unclear. We examined the
survival outcomes according to the results of donor age-based and graft volume
based analyses and assessed the impact of prognostic factors on the survival
after LDLT for elderly recipients. METHODS: The 198 adult recipients were
classified into 2 groups: an elderly group (n = 70, E group; >= 60 years of age)
and a younger group (n = 128, Y group; <60 years of age). We analyzed the
prognostic factors for the survival in the E group and the survival rate for both
groups at several follow-up points and conducted subgroup analyses in the E group
by combining the donor age (>=50 vs <50 years) and graft weight (GW)/standard
liver volume (SLV) (>=40% vs <40%). RESULTS: Donor age (hazard ratio [HR], 2.17;
P = 0.062) and GW/SLV (HR, 1.80; P = 0.23) tended to have a high HR in the E
group. The overall patient survival rates at 1, 3, and 5 years were 78.3%, 73.0%,
and 61.0% in the E group, and 82.0%, 75.1%, and 69.2% in the Y group,
respectively (P = 0.459). However, the outcomes tended to be worse in recipients
of grafts from donors >=50 years of age than in those with grafts from younger
donors with GW/SLV < 40% (P = 0.048). CONCLUSIONS: A worse outcome might be
associated with aging of the donor, which leads to impairment of the graft
function and liver regeneration. Both the graft volume and donor age should be
considered when choosing grafts for LDLT in elderly patients.
PMID- 28706972
TI - Fever and Pancytopenia in a Liver Transplant Recipient: Going Against the Rules
of Occam's Razor.
AB - The syndrome of fever and pancytopenia is not infrequently encountered postliver
transplant, and a broad differential list of infectious and noninfectious
aetiologies can be invoked. A transplant patient is susceptible to more than 1
opportunistic infection or disease process. We described the diagnostic
conundrums in managing our patient who ran a complex protracted course postliver
transplant. He was diagnosed to have both disseminated tuberculosis and graft
versus-host disease, a rare complication after solid organ transplantation.
PMID- 28706973
TI - Splenocyte Infusion and Whole-Body Irradiation for Induction of Peripheral
Tolerance in Porcine Lung Transplantation: Modifications of the Preconditioning
Regime for Improved Clinical Feasibility.
AB - BACKGROUND: Preoperative low-dose whole-body irradiation (IRR) with 1.5 and 7 Gy
thymic IRR of the recipient, combined with a perioperative donor splenocyte
infusion lead to reliable donor specific peripheral tolerance in our allogeneic
porcine lung transplantation model. To reduce the toxicity of this
preconditioning regime, modifications of the IRR protocol and their impact on
allograft survival were assessed. METHODS: Left-sided single lung transplantation
from major histocompatibility complex and sex mismatched donors was performed in
14 adult female minipigs. Recipient animals were exposed to 3 different protocols
of nonmyeloablative IRR within 12 hours before transplantation. All animals were
administered a donor splenocyte infusion on the day of lung transplantation.
Intravenous pharmacologic immunosuppression was withdrawn after 28 postoperative
days. Allograft survival was monitored by chest radiographs and bronchoscopy.
RESULTS: IRR prolonged transplant survival in a dose- and field-dependent manner.
Shielding of the bone marrow from IRR (total lymphoid IRR at 1.5 and 7 Gy thymic
IRR) significantly reduced protocol toxicity defined as thrombocytopenia and
consecutive increased bleeding propensity, but had a less effective impact on
graft survival. Whole-body IRR at 0.5 and 7 Gy thymic IRR proved to be
ineffective for reliable tolerance induction. Eventually, high levels of
circulating CD4+CD25high regulatory T cells were present in long-term survivors.
CONCLUSIONS: These data show that the infusion of donor-specific alloantigen in
combination with IRR is efficient once a threshold dose is exceeded.
PMID- 28706974
TI - Sirolimus Increases T-Cell Abundance in the Sun Exposed Skin of Kidney Transplant
Recipients.
AB - BACKGROUND: Kidney transplant recipients (KTRs) receiving the mammalian target of
rapamycin inhibitor sirolimus may display a reduced risk of skin cancer
development compared to KTRs receiving calcineurin inhibitors. Despite studies
investigating the effects of these 2 drug classes on T cells in patient blood,
the effect these drugs may have in patient skin is not yet known. METHODS:
Fifteen patients with chronic kidney disease (not recipients of immunosuppressive
drugs), and 30 KTRs (15 receiving a calcineurin inhibitor, and 15 receiving
sirolimus) provided matched samples of blood, sun exposed (SE) and non-SE skin.
The abundance of total CD8+ and CD4+ T cells, memory CD8+ and CD4+ T cells, and
regulatory T (Treg) cells in each sample was then assessed by flow cytometry.
RESULTS: Sirolimus treatment significantly increased absolute numbers of CD4+ T
cells, memory CD8+- and CD4+ T cells, and Treg cells in SE skin versus paired
samples of non-SE skin. No differences were found in the absolute number of any T
cell subset in the blood. Correlation analysis revealed that the percentage of T
cell subsets in the blood does not always accurately reflect the percentage of T
cell subsets in the skin of KTRs. Furthermore, sirolimus significantly disrupts
the balance of memory CD4+ T cells in the skin after chronic sun exposure.
CONCLUSIONS: This study demonstrated that immunosuppressive drug class and sun
exposure modify the abundance of multiple T-cell subsets in the skin of KTRs.
Correlation analysis revealed that the prevalence of Treg cells in KTR blood does
not accurately reflect the prevalence of Treg cells in KTR skin.
PMID- 28706975
TI - Reexamining the Association of Body Mass Index With Overall Survival Outcomes
After Liver Transplantation.
AB - BACKGROUND: Several studies have shown that obese patients undergoing liver
transplantation (LT) have an increased risk of mortality regardless of Model of
End Stage Liver Disease (MELD) scores. The purpose of this study is to identify
the range of body mass index (BMI) at LT associated with the lowest risks of
posttransplant mortality by MELD category. METHODS: A retrospective cohort of
patients aged 18 years or older from the Organ Procurement and Transplantation
Network database undergoing LT between February 27, 2002, and December 31, 2013,
was identified and followed up through March 14, 2014. Patients' MELD score at
the time of transplantation was categorized into 10 or lower (MELD1), 11 to 18
(MELD2), 19 to 24 (MELD3), and 25 or higher (MELD4). Multivariable adjusted Cox
proportional hazard analyses were conducted. RESULTS: Among 48 226 patients in
the analytic cohort (14.8% were in MELD1, 33.7% were in MELD2, 19.6% were in
MELD3, and 32.0% were in MELD4), 25% died with mean follow-up of 1371 days. For
MELD1, patient BMI ranging from 30 to 33 was associated with a better survival
outcome than BMI less than 30 or 33 or greater; for MELD2, BMI ranging from 28 to
37 had a better survival outcome than BMI less than 28 or 37 or greater; for
MELD3, the survival outcome improved with an increasing BMI; for MELD4, the
survival outcome was not associated with patient BMI. CONCLUSIONS: This study
provides evidence that obesity in LT patients is not necessarily associated with
higher posttransplantation mortality and highlights the importance of the
interaction between BMI and MELD category to determine their survival likelihood.
PMID- 28706976
TI - Donor Diabetes and Prolonged Cold Ischemia Time Synergistically Increase the Risk
of Graft Failure After Liver Transplantation.
AB - BACKGROUND: Both prolonged cold ischemia time (CIT) and donor history of diabetes
mellitus (DM) are associated with reduced graft survival after liver
transplantation. However, it is unknown whether the adverse effect of prolonged
CIT on posttransplant graft survival is more pronounced after transplant with DM
versus non-DM donor grafts. METHODS: The study sample included 58 226 liver
transplant recipients (2002-2015) from the Scientific Registry of Transplant
Recipients. Multivariable Cox survival regression with interaction analysis was
used to quantify the extent to which history of donor DM (n = 6478) potentiates
the adverse effect of prolonged (>=8 hours) CIT (n = 18 287) on graft survival.
RESULTS: Donor DM and CIT 8 hours or longer were each associated with increased
risk of graft failure (GF) (adjusted hazard ratio [aHR], 1.19; 95% confidence
interval [CI], 1.06-1.35 and aHR, 1.42; 95% CI, 1.32-1.53, respectively) compared
with transplanted grafts without either risk factor. However, the combination of
DM and CIT 8 hours or longer was associated with a higher risk of GF than either
factor alone (aHR, 1.79; 95% CI, 1.55-2.06) and had a synergy index of 1.30. The
interaction was significant on a multiplicative scale in the later postoperative
period, days 31 to 365 (P = 0.047). CONCLUSIONS: These results suggest that liver
grafts from DM donors are more susceptible to the adverse effects of prolonged
CIT than livers from non-DM donors. We need to be cognizant that they are more
susceptible to ischemic injury, and this may be considered during the allocation
process.
PMID- 28706977
TI - Acute Rejection After Kidney Transplantation Associates With Circulating
MicroRNAs and Vascular Injury.
AB - BACKGROUND: Acute rejection (AR) of kidney transplants is associated with the
loss of endothelial integrity, microvascular rarefaction and, ultimately, graft
dysfunction. Circulating angiogenic microRNAs (miRNAs) may serve as markers for
microvascular injury. Here, we investigated the short- and long-term effects of
AR after kidney transplantation on systemic vascular injury and the associated
circulating miRNA profile. METHODS: Systemic vascular injury was determined by
measuring capillary tortuosity and density within the oral mucosa as well as by
assessing circulating levels of angiopoietin-2/angiopoietin-1 ratio, vascular
endothelial growth factor and soluble thrombomodulin. After a pilot study, we
selected 48 miRNAs to assess the AR- and microvascular injury associated
circulating miRNAs. RESULTS: In stable transplant recipients (n = 25) and
patients with AR (n = 13), which were also studied longitudinally (1, 6, and 12
months post-AR), we found an AR-associated increase in markers of systemic
vascular injury, of which vascular endothelial growth factor and soluble
thrombomodulin normalized within 1 year after AR. Of the 48 selected miRNAs, 8
were either decreased (miR-135a, miR-199a-3p, and miR-15a) or increased (miR-17,
miR-140-3p, miR-130b, miR-122 and miR-192) in AR. Of these, miR-130b, miR-199a,
and miR-192 associated with markers of vascular injury, whereas miR-140-3p, miR
130b, miR-122, and miR-192 normalized within 1 year after AR. CONCLUSIONS: AR
after kidney transplantation is characterized by systemic microvascular injury
and associates with specific circulating miRNA levels.
PMID- 28706978
TI - Impact of Conversion From Advagraf to Twice-Daily Generic Tacrolimus in Kidney
Transplant Recipients: A Single-Center Study-A 3-Year Follow-Up.
PMID- 28706979
TI - The Optimization of Short-Term Hepatocyte Preservation Before Transplantation.
AB - BACKGROUND: No optimal methods for short-term hepatocyte preservation have been
established. We have recently developed a prominent oxygen-permeable bag (Tohoku
Device [TD]) for pancreatic islet culture and transplantation. In this study, we
investigated whether TD is also effective for hepatocyte preservation and tried
to optimize other conditions. METHODS: Hepatocytes were preserved in the
following conditions, and their outcomes were observed. First, the effectiveness
of TD was investigated. Second, hepatocyte medium (HM) and organ preservation
solutions with or without fetal bovine serum (FBS) were compared. Third, as
supplementations, FBS and human serum albumin (HSA) were compared. Fourth, low,
room and high temperature were compared. And finally, hepatocytes preserved in
various conditions were transplanted into the subrenal capsule space of
nonalbumin rats and engrafted areas were assessed. RESULTS: The survival rate of
hepatocytes preserved in TD tended to be higher and their viability and function
were maintained significantly greater than those of non-TD group. Irrespective of
FBS supplementation, the survival rate of HM group was significantly higher than
those of organ preservation solution group while viabilities and plating
efficiency were similar among them. Although survival rates of groups without FBS
were extremely low, results of HSA supplemented group were not inferior to FBS
supplemented group. Hepatocytes preserved at high temperature had the worst
results. The engrafted area of TD group tended to be higher than those of other
groups. CONCLUSIONS: TD is effective for short-term hepatocyte preservation. HSA
is a useful substitute for FBS, and preserving in HM at low temperature is
recommended.
PMID- 28706980
TI - Impact of Cold Ischemia Time in Kidney Transplants From Donation After
Circulatory Death Donors.
AB - BACKGROUND: Deceased-donor kidneys are exposed to ischemic events from donor
instability during the process of donation after circulatory death (DCD).
Clinicians may be reluctant to transplant DCD kidneys with prolonged cold
ischemia time (CIT) for fear of an additional deleterious effect. METHODS: We
performed a retrospective cohort study examining US registry data between 1998
and 2013 of adult first-time kidney-only recipients of paired kidneys (derived
from the same donor transplanted into different recipients) from DCD donors.
RESULTS: On multivariable analysis, death-censored graft survival (DCGS) was
comparable between recipients of kidneys with higher CIT relative to paired donor
recipients with lower CIT when the CIT difference was 1 hour or longer (adjusted
hazard ratio, [aHR], 1.02; 95% confidence interval [CI], 0.88-1.17; n = 6276), 5
hours or longer (aHR, 0.98; 95% CI, 0.80-1.19; n = 3130), 10 hours or longer
(aHR, 1.15; 95% CI, 0.82-1.60; n = 1124) or 15 hours (aHR, 1.15; 95% CI, 0.66
1.99; n = 498). There was a higher rate of primary non function in the long CIT
groups for delta 1 hour or longer (0.89% vs 1.63%; P = 0.006), 5 hours (1.09% vs
1.67%, P = 0.13); 10 hours (0.53% vs 1.78%; P = 0.03), and 15 hours (0.40% vs
1.61%; P = 0.18), respectively. Between each of the 4 delta CIT levels of shorter
and longer CIT, there was a significantly and incrementally higher rate of
delayed graft function in the long CIT groups for delta 1 hour or longer (37.3%
vs 41.7%; P < 0.001), 5 hours (35.9% vs 42.7%; P < 0.001), 10 hours (29.4% vs
44.2%, P < 0.001), and 15 hours (29.6% vs 46.1%, P < 0.001), respectively.
Overall patient survival was comparable with delta CITs of 1 hour or longer (aHR,
0.96; 95% CI, 0.84-1.08), 5 hours (aHR, 1.01; 95% CI, 0.85-1.20), and 15 hours
(aHR, 1.27; 95% CI, 0.79-2.06) but not 10 hours (aHR, 1.47; 95% CI, 1.09-1.98).
CONCLUSIONS: These results suggest that in the setting of a prior ischemic donor
event, prolonged CIT has limited bearing on long-term outcomes.
PMID- 28706981
TI - Outcomes of Liver Transplant Recipients With Autoimmune Liver Disease Using Long
Term Dual Immunosuppression Regimen Without Corticosteroid.
AB - BACKGROUND: Liver transplant (LT) recipients with autoimmune liver disease
(primary sclerosing cholangitis, primary biliary cholangitis, autoimmune
hepatitis) are at increased risk of developing acute cellular rejection (ACR),
and in many cases graft failure due to recurrent disease. We describe our
experience with dual immunosuppression without steroid maintenance and analyze
its effect on disease recurrence; ACR; patient and graft survivals; and
complications, such as sepsis and de novo malignancy. METHODS: We included 74
consecutive LT recipients (April 2006 to April 2013) with autoimmune liver
disease (primary sclerosing cholangitis, 20; primary biliary cholangitis, 23;
autoimmune hepatitis, 31) from a single transplant center. Immunosuppression
protocol included rabbit antithymocyte globulin for induction and mycophenolate
mofetil with tacrolimus or sirolimus/everolimus indefinitely for maintenance.
RESULTS: Overall 1-, 3-, 5-, and 7-year patient survival was 95.9%, 90.4%, 82,2%
and 74.9%, re-graft-free survival was 93.2%, 86.3%, 79.9%, and 72.8%,
respectively (median follow-up, 5.5 years). In a multivariate Cox regression
analysis, sepsis during post-LT period (P = 0.040; hazard ratio [HR], 2.52; 95%
confidence interval [CI], 1.04-6.11), steroid use for ACR (P = 0.037; HR, 2.60;
95% CI, 1.06-6.34), and younger age (<40 years) at LT (P = 0.038; HR, 2.53; 95%
CI, 1.05-6.10) predicted graft survival, whereas steroid use for ACR was the only
variable that was predictive of overall patient survival (P = 0.004; HR, 4.10;
95% CI, 1.59-10.52). Overall, 34 biopsy-proven ACR was noted in 22 LT recipients
(30%), 13 (17.5%) had disease recurrence, and 34 episodes of sepsis occurred in
19 patients. CONCLUSIONS: Dual immunosuppression protocol in LT recipients with
autoimmune liver disease without corticosteroid maintenance had acceptable rates
of survival and ACR without predisposing patients to the adverse effects of long
term steroid therapy.
PMID- 28706982
TI - Preserving the Pancreas Graft: Outcomes of Surgical Repair of Duodenal Leaks in
Enterically Drained Pancreas Allografts.
AB - BACKGROUND: Duodenal leak remains a major cause of morbidity and graft loss in
pancreas transplant recipients. The role and efficacy of surgical and image
guided interventions to salvage enterically drained grafts with a duodenal leak
has yet to be defined. METHODS: We investigated the incidence, treatment, and
outcome of duodenal leak in 426 pancreas transplantation recipients from 2000 to
2015. RESULTS: Duodenal leak developed in 33 (7.8%) recipients after a median
follow-up of 5.3 (range, 0.5-15.2) years. Most leaks occurred during the first
year (n = 22; 67%), and most were located near the proximal and distal duodenal
staple line. Graft pancreatectomy was performed in 8 patients as primary therapy
because of unfavorable local and/or systemic conditions. Salvage was attempted in
25 patients using percutaneous drainage (n = 4), surgical drainage (n = 4), or
surgical repair (n = 17). Percutaneous or surgical drainage failed to control the
leak in 7 of these 8 patients, and all 7 ultimately required graft pancreatectomy
for persistent leak and sepsis. Surgical repair salvaged 14 grafts, and 13 grafts
continue to function after a median follow-up of 2.9 (range, 1.1-6.3) years after
repair. CONCLUSIONS: Our study shows that in selected patients a duodenal leak
can be repaired successfully and safely in enterically drained grafts.
PMID- 28706983
TI - Preimplantation Kidney Biopsies of Extended Criteria Donors Have a Heavier
Inflammatory Burden Than Kidneys From Standard Criteria Donors.
AB - BACKGROUND: Donors after brain death develop a systemic proinflammatory state
that may predispose the kidneys to injury after transplantation. Because it is
not known whether this inflammatory environment similarly affects the kidneys
from expanded criteria donor (ECD) and standard criteria donors (SCD), we sought
to evaluate differences in the gene expression of inflammatory cytokines in
preimplantation biopsies (PIBx) from ECD and SCD kidneys. METHODS: Cytokines gene
expression was measured in 80 PIBx (SCD, 52; ECD, 28) and associated with donor
variables. RESULTS: Normal histology and chronic histological lesions were not
different between both types of kidneys. ECD kidneys showed significant increase
in the transcripts of MCP-1, RANTES, TGF-beta1, and IL-10 when compared with SCD.
Kidneys presenting normal histology had similar inflammatory profile except by a
higher expression of RANTES observed in ECD (P = 0.04). Interstitial fibrosis and
tubular atrophy (interstitial fibrosis and tubular atrophy >= 1) were associated
with higher expression of TGF-beta1, RANTES, and IL-10 in ECD compared with SCD
kidneys. Cold ischemia time of 24 hours or longer was significantly associated
with upregulation of FOXP3, MCP-1, RANTES, and IL10, whereas longer duration of
donor hospitalization significantly increased gene expression of all markers.
High FOXP3 expression was also associated with lower level of serum creatinine at
1 year. Donor age was not associated with any of the transcripts studied.
CONCLUSIONS: PIBx of ECD exhibit a higher gene expression of inflammatory
cytokines when compared with SCD kidneys. This molecular profile may be a
specific ECD kidney response to brain death and may help to predict the
posttransplant outcomes of ECD recipients.
PMID- 28706984
TI - The UK National Registry of ABO and HLA Antibody Incompatible Renal
Transplantation: Pretransplant Factors Associated With Outcome in 879
Transplants.
AB - BACKGROUND: ABO and HLA antibody incompatible (HLAi) renal transplants (AIT) now
comprise around 10% of living donor kidney transplants. However, the relationship
between pretransplant factors and medium-term outcomes are not fully understood,
especially in relation to factors that may vary between centers. METHODS: The
comprehensive national registry of AIT in the United Kingdom was investigated to
describe the donor, recipient and transplant characteristics of AIT. Kaplan-Meier
analysis was used to compare survival of AIT to all other compatible kidney
transplants performed in the United Kingdom. Cox proportional hazards regression
modeling was used to determine which pretransplant factors were associated with
transplant survival in HLAi and ABOi separately. The primary outcome was
transplant survival, taking account of death and graft failure. RESULTS: For 522
HLAi and 357 ABO incompatible (ABOi) transplants, 5-year transplant survival
rates were 71% (95% confidence interval [CI], 66-75%) for HLAi and 83% (95% CI,
78-87%) for ABOi, compared with 88% (95% CI, 87-89%) for 7290 standard living
donor transplants, and 78% (95% CI, 77-79%) for 15 322 standard deceased donor
transplants (P < 0.0001). Increased chance of transplant loss in HLAi was
associated with increasing number of donor specific HLA antibodies, center
performing the transplant, antibody level at the time of transplant, and an
interaction between donor age and dialysis status. In ABOi, transplant loss was
associated with no use of IVIg, cytomegalovirus seronegative recipient, 000 HLA
donor-recipient mismatch; and increasing recipient age. CONCLUSIONS: Results of
AIT were acceptable, certainly in the context of a choice between living donor
AIT and an antibody compatible deceased donor transplant. Several factors were
associated with increased chance of transplant loss, and these can lead to
testable hypotheses for further improving therapy.
PMID- 28706985
TI - Clinical Utility of Epstein-Barr Virus Viral Load Monitoring and Risk Factors for
Posttransplant Lymphoproliferative Disorders After Kidney Transplantation: A
Single-Center, 10-Year Observational Cohort Study.
AB - BACKGROUND: Posttransplant lymphoproliferative disease (PTLD) is an important
cause of morbidity and mortality in solid organ transplants. Epstein Barr virus
(EBV) plays a major role in PTLD development. Guidelines recommend EBV viral load
(VL) monitoring in high-risk populations in the first year. METHODS:
Retrospective observational study in all adult patients who had at least 1 EBV-VL
performed in the postkidney transplant (KT) period from January 2005 to December
2014 at the Policlinico Modena Hospital. We compared patients with negative EBV
DNA to patients with positive EBV-DNA and we described PTLD developed in the
study period. RESULTS: One hundred ninety (36.3%) KT patients of 523 were
screened for EBV-DNA with 796 samples. One hundred twenty-eight (67.4%) of 190
tested patients presented at least 1 positive sample for EBV. Older age, the use
of sirolimus, everolimus, and steroids were associated with EBV-DNA positivity in
the univariate analysis. Nine (1.7%) of 523 patients had PTLD. Incidence rate of
PTLD in the KT cohort was 0.19/100 person year follow-up (95% confidence
interval, 0.09-0.37). One of 9 patients developed early PTLD and was a high-risk
patient. Only this PTLD case was positive for EBV. No PTLD case had an EBV-VL
superior to 4000 copies/mL. CONCLUSIONS: Our results suggest that the keystone of
PTLD diagnosis is the clinical suspicion. Our study suggests that, in line with
guidelines, EBV-VL assays may be avoided in low-risk patients in the absence of a
strong clinical PTLD suspicion without increasing patients' risk of developing
PTLD. This represents a safe and cost-saving clinical strategy for our center.
PMID- 28706986
TI - Liver Preservation by Aortic Perfusion Alone Compared With Preservation by Aortic
Perfusion and Additional Arterial Ex Situ Back-Table Perfusion With Histidine
Tryptophan-Ketoglutarate Solution: A Prospective, Randomized, Controlled,
Multicenter Study.
AB - BACKGROUND: Arterial ex situ back-table perfusion (BP) reportedly reduces
ischemic-type biliary lesion after liver transplantation. We aimed to verify
these findings in a prospective investigation. METHODS: Our prospective,
randomized, controlled, multicenter study involved livers retrieved from patients
in 2 German regions, and compared the outcomes of standard aortic perfusion to
those of aortic perfusion combined with arterial ex situ BP. The primary endpoint
was the incidence of ischemic-type biliary lesions over a follow-up of 2 years
after liver transplantation, whereas secondary endpoints included 2-year graft
survival, initial graft damage as reflected by transaminase levels, and
functional biliary parameters at 6 months after transplantation. RESULTS: A total
of 75 livers preserved via standard aortic perfusion and 75 preserved via
standard aortic perfusion plus arterial BP were treated using a standardized
protocol. The incidence of clinically apparent biliary lesions after liver
transplantation (n = 9 for both groups; P = 0.947), the 2-year graft survival
rate (standard aortic perfusion, 74%; standard aortic perfusion plus arterial BP,
68%; P = 0.34), and incidence of initial graft injury did not differ between the
2 perfusion modes. Although 33 of the 77 patients with cholangiography workups
exhibited injured bile ducts, only 10 had clinical symptoms. CONCLUSIONS:
Contrary to previous findings, the present study indicated that additional ex
situ BP did not prevent ischemic-type biliary lesions or ischemia-reperfusion
injury after liver transplantation. Moreover, there was considerable discrepancy
between cholangiography findings regarding bile duct changes and clinically
apparent cholangiopathy after transplantation, which should be considered when
assessing ischemic-type biliary lesions.
PMID- 28706987
TI - Influence of Cold Ischemia Time in Kidney Transplants From Small Pediatric
Donors.
AB - BACKGROUND: Clinicians may be reluctant to transplant small pediatric kidneys
that have prolonged cold ischemia time (CIT) for fear of an additional
deleterious effect because pediatric grafts are thought to be more sensitive to
ischemia. We aimed to assess the risks associated with transplantation of small
pediatric kidneys with prolonged CIT. METHODS: We performed a retrospective
cohort study examining US registry data between 1998 and 2013 of adult first-time
kidney-only recipients of small pediatric kidneys from donors weighing 10 to 20
kg, stratified by CIT levels of 0 to 18 (n = 1413), 19 to 30 (n = 1116), and
longer than 30 (n = 338) hours. RESULTS: All-cause graft survival by CIT groups
at 1-year was 92%, 88%, and 89%, respectively. 1-year risk-adjusted graft
survival hazard ratios were significantly higher with CIT of 19 to 30 hours
(adjusted hazard ratios, 1.37; 95% confidence interval, 1.04-1.81) and somewhat
higher with CIT greater than 30 hours (adjusted hazard ratios, 1.24; 95%
confidence interval, 0.82-1.88) relative to recipients with CIT 0 to 18 hours.
There was little variation in the effect of CIT on graft survival when restricted
to single kidney transplants only and no significant interaction of CIT category
and single kidney transplantation (P = 0.93). CONCLUSIONS: Although prolonged CIT
is associated with lower early graft survival in small pediatric donor kidney
transplants, absolute decreases in 1-year graft survival rates were 3% to 4%.
PMID- 28706988
TI - Unsustainable development pathways caused by tropical deforestation.
AB - Global sustainability strategies require assessing whether countries' development
trajectories are sustainable over time. However, sustainability assessments are
limited because losses of natural capital and its ecosystem services through
deforestation have not been comprehensively incorporated into national accounts.
We update the national accounts of 80 nations that underwent tropical
deforestation from 2000 to 2012 and evaluate their development trajectories using
weak and strong sustainability criteria. Weak sustainability requires that
countries do not decrease their aggregate capital over time. We adopt a strong
sustainability criterion that countries do not decrease the value of their forest
ecosystem services with respect to the year 2000. We identify several groups of
countries: countries, such as Sri Lanka, Bangladesh, and India, that present
sustainable development trajectories under both weak and strong sustainability
criteria; countries, such as Brazil, Peru, and Indonesia, that present weak
sustainable development but fail the strong sustainability criterion as a result
of rapid losses of ecosystem services; countries, such as Madagascar, Laos, and
Papua New Guinea, that present unsustainable development pathways as a result of
deforestation; and countries, such as Democratic Republic of Congo and Sierra
Leone, in which deforestation aggravates already unsustainable pathways. Our
results reveal a large number of countries where tropical deforestation is both
damaging to nature and not compensated by development in other sectors, thus
compromising the well-being of their future generations.
PMID- 28706989
TI - Inactivation of thermogenic UCP1 as a historical contingency in multiple
placental mammal clades.
AB - Mitochondrial uncoupling protein 1 (UCP1) is essential for nonshivering
thermogenesis in brown adipose tissue and is widely accepted to have played a key
thermoregulatory role in small-bodied and neonatal placental mammals that enabled
the exploitation of cold environments. We map ucp1 sequences from 133 mammals
onto a species tree constructed from a ~51-kb sequence alignment and show that
inactivating mutations have occurred in at least 8 of the 18 traditional
placental orders, thereby challenging the physiological importance of UCP1 across
Placentalia. Selection and timetree analyses further reveal that ucp1
inactivations temporally correspond with strong secondary reductions in metabolic
intensity in xenarthrans and pangolins, or in six other lineages coincided with a
~30 million-year episode of global cooling in the Paleogene that promoted sharp
increases in body mass and cladogenesis evident in the fossil record. Our
findings also demonstrate that members of various lineages (for example,
cetaceans, horses, woolly mammoths, Steller's sea cows) evolved extreme cold
hardiness in the absence of UCP1-mediated thermogenesis. Finally, we identify
ucp1 inactivation as a historical contingency that is linked to the current low
species diversity of clades lacking functional UCP1, thus providing the first
evidence for species selection related to the presence or absence of a single
gene product.
PMID- 28706990
TI - Distinct distributed patterns of neural activity are associated with two
languages in the bilingual brain.
AB - A large body of previous neuroimaging studies suggests that multiple languages
are processed and organized in a single neuroanatomical system in the bilingual
brain, although differential activation may be seen in some studies because of
different proficiency levels and/or age of acquisition of the two languages.
However, one important possibility is that the two languages may involve
interleaved but functionally independent neural populations within a given
cortical region, and thus, distinct patterns of neural computations may be
pivotal for the processing of the two languages. Using functional magnetic
resonance imaging (fMRI) and multivariate pattern analyses, we tested this
possibility in Chinese-English bilinguals when they performed an implicit reading
task. We found a broad network of regions wherein the two languages evoked
different patterns of activity, with only partially overlapping patterns of
voxels in a given region. These regions, including the middle occipital cortices,
fusiform gyri, and lateral temporal, temporoparietal, and prefrontal cortices,
are associated with multiple aspects of language processing. The results suggest
the functional independence of neural computations underlying the representations
of different languages in bilinguals.
PMID- 28706991
TI - Multiplexed gene control reveals rapid mRNA turnover.
AB - The rates of mRNA synthesis and decay determine the mRNA expression level. The
two processes are under coordinated control, which makes the measurements of
these rates challenging, as evidenced by the low correlation among the methods of
measurement of RNA half-lives. We developed a minimally invasive method,
multiplexed gene control, to shut off expression of genes with controllable
synthetic promoters. The method was validated by measuring the ratios of the
nascent to mature mRNA molecules and by measuring the half-life with endogenous
promoters that can be controlled naturally or through inserting short sequences
that impart repressibility. The measured mRNA half-lives correlated highly with
those obtained with the metabolic pulse-labeling method in yeast. However, mRNA
degradation was considerably faster in comparison to previous estimates, with a
median half-life of around 2 min. The half-life permits the estimation of
promoter-dependent and promoter-independent transcription rates. The dynamical
range of the promoter-independent transcription rates was larger than that of the
mRNA half-lives. The rapid mRNA turnover and the broad adjustability of promoter
independent transcription rates are expected to have a major impact on stochastic
gene expression and gene network behavior.
PMID- 28706992
TI - Electrochemical electron beam lithography: Write, read, and erase metallic
nanocrystals on demand.
AB - We develop a solution-based nanoscale patterning technique for site-specific
deposition and dissolution of metallic nanocrystals. Nanocrystals are grown at
desired locations by electron beam-induced reduction of metal ions in solution,
with the ions supplied by dissolution of a nearby electrode via an applied
potential. The nanocrystals can be "erased" by choice of beam conditions and
regrown repeatably. We demonstrate these processes via in situ transmission
electron microscopy using Au as the model material and extend to other metals. We
anticipate that this approach can be used to deposit multicomponent alloys and
core-shell nanostructures with nanoscale spatial and compositional resolutions
for a variety of possible applications.
PMID- 28706993
TI - High frequency of intestinal TH17 cells correlates with microbiota alterations
and disease activity in multiple sclerosis.
AB - T helper 17 (TH17) cells are key players in multiple sclerosis (MS), and studies
in animal models demonstrated that effector TH17 cells that trigger brain
autoimmunity originate in the intestine. We validate in humans the crucial role
of the intestinal environment in promoting TH17 cell expansion in MS patients. We
found that increased frequency of TH17 cells correlates with high disease
activity and with specific alterations of the gut mucosa-associated microbiota in
MS patients. By using 16S ribosomal RNA sequencing, we analyzed the microbiota
isolated from small intestinal tissues and found that MS patients with high
disease activity and increased intestinal TH17 cell frequency showed a higher
Firmicutes/Bacteroidetes ratio, increased relative abundance of Streptococcus,
and decreased Prevotella strains compared to healthy controls and MS patients
with no disease activity. We demonstrated that the intestinal TH17 cell frequency
is inversely related to the relative abundance of Prevotella strains in the human
small intestine. Our data demonstrate that brain autoimmunity is associated with
specific microbiota modifications and excessive TH17 cell expansion in the human
intestine.
PMID- 28706994
TI - Short-range surface plasmonics: Localized electron emission dynamics from a 60-nm
spot on an atomically flat single-crystalline gold surface.
AB - We experimentally and theoretically visualize the propagation of short-range
surface plasmon polaritons using atomically flat single-crystalline gold
platelets on silicon substrates. We study their excitation and subfemtosecond
dynamics via normal-incidence two-photon photoemission electron microscopy. By
milling a plasmonic disk and grating structure into a single-crystalline gold
platelet, we observe nanofocusing of the short-range surface plasmon polariton.
Localized two-photon ultrafast electron emission from a spot with a smallest
dimension of 60 nm is observed. Our novel approach opens the door toward
reproducible plasmonic nanofocusing devices, which do not degrade upon high light
intensity or heating due to the atomically flat surface without any tips,
protrusions, or holes. Our nanofoci could also be used as local emitters for
ultrafast electron bunches in time-resolved electron microscopes.
PMID- 28706995
TI - Disabling Cas9 by an anti-CRISPR DNA mimic.
AB - CRISPR (clustered regularly interspaced short palindromic repeats)-Cas9 gene
editing technology is derived from a microbial adaptive immune system, where
bacteriophages are often the intended target. Natural inhibitors of CRISPR-Cas9
enable phages to evade immunity and show promise in controlling Cas9-mediated
gene editing in human cells. However, the mechanism of CRISPR-Cas9 inhibition is
not known, and the potential applications for Cas9 inhibitor proteins in
mammalian cells have not been fully established. We show that the anti-CRISPR
protein AcrIIA4 binds only to assembled Cas9-single-guide RNA (sgRNA) complexes
and not to Cas9 protein alone. A 3.9 A resolution cryo-electron microscopy
structure of the Cas9-sgRNA-AcrIIA4 complex revealed that the surface of AcrIIA4
is highly acidic and binds with a 1:1 stoichiometry to a region of Cas9 that
normally engages the DNA protospacer adjacent motif. Consistent with this binding
mode, order-of-addition experiments showed that AcrIIA4 interferes with DNA
recognition but has no effect on preformed Cas9-sgRNA-DNA complexes. Timed
delivery of AcrIIA4 into human cells as either protein or expression plasmid
allows on-target Cas9-mediated gene editing while reducing off-target edits.
These results provide a mechanistic understanding of AcrIIA4 function and
demonstrate that inhibitors can modulate the extent and outcomes of Cas9-mediated
gene editing.
PMID- 28706996
TI - South African Breast Cancer and HIV Outcomes Study: Methods and Baseline
Assessment.
AB - PURPOSE: In low- and middle-income, HIV-endemic regions of sub-Saharan Africa,
morbidity and mortality from the common epithelial cancers of the developed world
are rising. Even among HIV-infected individuals, access to antiretroviral therapy
has enhanced life expectancy, shifting the distribution of cancer diagnoses
toward non-AIDS-defining malignancies, including breast cancer. Building on our
prior research, we recently initiated the South African Breast Cancer and HIV
Outcomes study. METHODS: We will recruit a cohort of 3,000 women newly diagnosed
with breast cancer at hospitals in high (average, 20%) HIV prevalence areas, in
Johannesburg, Durban, Pietermaritzburg, and Empangeni. At baseline, we will
collect information on demographic, behavioral, clinical, and other factors
related to access to health care. Every 3 months in year 1 and every 6 months
thereafter, we will collect interview and chart data on treatment, symptoms,
cancer progression, comorbidities, and other factors. We will compare survival
rates of HIV-infected and uninfected women with newly diagnosed breast cancer and
their likelihood of receiving suboptimal anticancer therapy. We will identify
determinants of suboptimal therapy and context-specific modifiable factors that
future interventions can target to improve outcomes. We will explore molecular
mechanisms underlying potentially aggressive breast cancer in both HIV-infected
and uninfected patients, as well as the roles of pathogens, states of immune
activation, and inflammation in disease progression. CONCLUSION: Our goals are to
contribute to development of evidence-based guidelines for the management of
breast cancer in HIV-positive women and to improve outcomes for all patients with
breast cancer in resource-constrained settings.
PMID- 28706997
TI - Childhood forecasting of a small segment of the population with large economic
burden.
AB - Policy-makers are interested in early-years interventions to ameliorate childhood
risks. They hope for improved adult outcomes in the long run, bringing return on
investment. How much return can be expected depends, partly, on how strongly
childhood risks forecast adult outcomes. But there is disagreement about whether
childhood determines adulthood. We integrated multiple nationwide administrative
databases and electronic medical records with the four-decade Dunedin birth
cohort study to test child-to-adult prediction in a different way, by using a
population-segmentation approach. A segment comprising one-fifth of the cohort
accounted for 36% of the cohort's injury insurance-claims; 40% of excess obese
kilograms; 54% of cigarettes smoked; 57% of hospital nights; 66% of welfare
benefits; 77% of fatherless childrearing; 78% of prescription fills; and 81% of
criminal convictions. Childhood risks, including poor age-three brain health,
predicted this segment with large effect sizes. Early-years interventions
effective with this population segment could yield very large returns on
investment.
PMID- 28706998
TI - The Extended Erlang-Truncated Exponential distribution: Properties and
application to rainfall data.
AB - The Erlang-Truncated Exponential ETE distribution is modified and the new
lifetime distribution is called the Extended Erlang-Truncated Exponential EETE
distribution. Some statistical and reliability properties of the new distribution
are given and the method of maximum likelihood estimate was proposed for
estimating the model parameters. The usefulness and flexibility of the EETE
distribution was illustrated with an uncensored data set and its fit was compared
with that of the ETE and three other three-parameter distributions. Results based
on the minimized log-likelihood ([Formula: see text]), Akaike information
criterion (AIC), Bayesian information criterion (BIC) and the generalized Cramer
von Mises [Formula: see text] statistics shows that the EETE distribution
provides a more reasonable fit than the one based on the other competing
distributions.
PMID- 28706999
TI - Ecological connectivity networks in rapidly expanding cities.
AB - Urban expansion increases fragmentation of the landscape. In effect,
fragmentation decreases connectivity, causes green space loss and impacts upon
the ecology and function of green space. Restoration of the functionality of
green space often requires restoring the ecological connectivity of this green
space within the city matrix. However, identifying ecological corridors that
integrate different structural and functional connectivity of green space remains
vague. Assessing connectivity for developing an ecological network by using
efficient models is essential to improve these networks under rapid urban
expansion. This paper presents a novel methodological approach to assess and
model connectivity for the Eurasian tree sparrow (Passer montanus) and Yellow
vented bulbul (Pycnonotus goiavier) in three cities (Kuala Lumpur, Malaysia;
Jakarta, Indonesia and Metro Manila, Philippines). The approach identifies
potential priority corridors for ecological connectivity networks. The study
combined circuit models, connectivity analysis and least-cost models to identify
potential corridors by integrating structure and function of green space patches
to provide reliable ecological connectivity network models in the cities.
Relevant parameters such as landscape resistance and green space structure
(vegetation density, patch size and patch distance) were derived from an expert
and literature-based approach based on the preference of bird behaviour. The
integrated models allowed the assessment of connectivity for both species using
different measures of green space structure revealing the potential corridors and
least-cost pathways for both bird species at the patch sites. The implementation
of improvements to the identified corridors could increase the connectivity of
green space. This study provides examples of how combining models can contribute
to the improvement of ecological networks in rapidly expanding cities and
demonstrates the usefulness of such models for biodiversity conservation and
urban planning.
PMID- 28707000
TI - Inducing maternal inflammation promotes leptin production in offspring but does
not improve allergic symptoms in a mouse model of allergic rhinitis.
AB - AIMS: The intrauterine environment is considered to affect immunological
development in fetus, leading to an increased risk of developing allergy. In
particular, maternal lipopolysaccharides (LPS) administration might regulate the
development of allergic disease in offspring. Several studies have shown that
being obese relates to a higher prevalence of allergic diseases compared to
normal weight. The present study explored the effects of inducing maternal
inflammation with LPS before pregnancy on body weight, physical composition
including body fat, adipokine production, and pathology of allergic rhinitis in
offspring. MAIN METHODS: Female mice received a single intraperitoneal injection
of LPS (2 MUg/g BW). After 5 days of LPS administration, female mice were mated
with males, and experimental allergic rhinitis was induced in female offspring.
Immunization and nasal challenge with ovalbumin (OVA) were performed at 7 and 8
weeks of age. Allergic rhinitis-like symptoms, OVA-specific IgE and adipokines in
sera, body weight, fat pad weight, and cytokine production by splenocytes in
these 9-week-old offspring. KEY FINDINGS: Maternal LPS administration results in
a significant increase in body weight, visceral fat accumulation, and serum
leptin concentration, and the dominance of Th1 in Th balance. Nevertheless, there
was no statistical difference in OVA-specific IgE titer and allergic-like
symptoms between the groups. SIGNIFICANCE: In conclusion, maternal LPS promoted
leptin production and altered Th balance in mice offspring, but not improved
allergic symptoms in a mouse model of allergic rhinitis. It might suggest that
inflammation during pregnancy plays a role in the adipose tissue function which
could diversely influence allergic inflammation in offspring.
PMID- 28707001
TI - Abdominal symptoms in general practice: Frequency, cancer suspicions raised, and
actions taken by GPs in six European countries. Cohort study with prospective
registration of cancer.
AB - BACKGROUND: Abdominal symptoms are diagnostically challenging to general
practitioners (GPs): although common, they may indicate cancer. In a prospective
cohort of patients, we examined abdominal symptom frequency, initial diagnostic
suspicion, and actions of GPs in response to abdominal symptoms. METHODS: Over a
10-day period, 493 GPs in Norway, Denmark, Sweden, Belgium, the Netherlands, and
Scotland, recorded consecutive consultations: sex, date of birth and any
specified abdominal symptoms. For patients with abdominal symptoms, additional
data on non-specific symptoms, GPs' diagnostic suspicion, and features of the
consultation were noted. Data on all cancer diagnoses among all included patients
were requested from the GPs eight months later. FINDINGS: Consultations with
61802 patients were recorded. Abdominal symptoms were recorded in 6264 (10.1%)
patients. A subsequent malignancy was reported in 511 patients (0.8%): 441
(86.3%) had a new cancer, 70 (13.7%) a recurrent cancer. Abdominal symptoms were
noted in 129 (25.2%) of cancer patients (P < 0.001), rising to 34.5% for the 89
patients with cancer located in the abdominal region. PPV for any cancer given
any abdominal symptom was 2.1%. In symptomatic patients diagnosed with cancer,
GPs noted a suspicion of cancer for 85 (65.9%) versus 1895 (30.9%) when there was
no subsequent cancer (P < 0.001). No suspicion was noted in 32 (24.8%) cancer
patients. The GP's intuitive cancer suspicion was independently associated with a
subsequent new cancer diagnosis (OR 2.11, 95% CI 1.15-3.89). Laboratory tests
were ordered for 45.4% of symptomatic patients, imaging for 10.4%, referral or
hospitalization for 20.0%: all were more frequent in subsequent cancer patients
(P < 0.001). INTERPRETATION: Abdominal symptoms pointed to abdominal cancers
rather than to other cancers. However, the finding of abdominal symptoms in only
one third of patients with an abdominal cancer, and the lack of cancer suspicion
in a quarter of symptomatic cancer patients, provide challenges for GPs'
diagnostic thinking and referral practices.
PMID- 28707002
TI - Epigenetic regulation of cellular and cytomegalovirus genes during myeloid cell
development.
AB - Myeloid cells are important cell types that carry human cytomegalovirus. Latent
viral DNA is present in CD34+ progenitor cells and their derived monocytes.
However, differentiation of latently infected monocytes to mature macrophages or
dendritic cells causes reactivation of latent viruses. During hematopoietic
development, pluripotent genes are repressed, and lineage specific genes are
activated in a step-wise manner. This process is governed by cell-type specific
chromatin states. Enhancers in the hematopoietic system are highly dynamic and
established by pioneer (first tier) transcription factors (TFs), which set the
stage for second and third tier TF binding. In this review, we examine the
epigenetic mechanisms that regulate myeloid cell development, cell identity, and
activation with a special focus on factors that regulate viral gene expression
and the status of viral infection in myeloid cells.
PMID- 28707003
TI - Up-regulation of LFA-1 allows liver-resident memory T cells to patrol and remain
in the hepatic sinusoids.
AB - Liver-resident CD8+ T cells are highly motile cells that patrol the vasculature
and provide protection against liver pathogens. A key question is: how can these
liver CD8+ T cells be simultaneously present in the circulation and tissue
resident? Because liver-resident T cells do not express CD103 - a key integrin
for T cell residence in epithelial tissues - we investigated other candidate
adhesion molecules. Using intra-vital imaging we found that CD8+ T cell
patrolling in the hepatic sinusoids is dependent upon LFA-1-ICAM-1 interactions.
Interestingly, liver-resident CD8+ T cells up-regulate LFA-1 compared to effector
memory cells, presumably to facilitate this behavior. Finally, we found that LFA
1 deficient CD8+ T cells failed to form substantial liver-resident memory
populations following Plasmodium or LCMV immunization. Collectively, our results
demonstrate that it is adhesion through LFA-1 that allows liver-resident memory
CD8+ T cells to patrol and remain in the hepatic sinusoids.
PMID- 28707004
TI - Host sirtuin 1 regulates mycobacterial immunopathogenesis and represents a
therapeutic target against tuberculosis.
AB - Mycobacterium tuberculosis (Mtb) executes a plethora of immune-evasive
mechanisms, which contribute to its pathogenesis, limited efficacy of current
therapy, and the emergence of drug-resistant strains. This has led to resurgence
in attempts to develop new therapeutic strategies/targets against tuberculosis
(TB). We show that Mtb down-regulates sirtuin 1 (SIRT1), a nicotinamide adenine
dinucleotide (NAD+)-dependent deacetylase, in monocytes/macrophages, TB animal
models, and TB patients with active disease. Activation of SIRT1 reduced
intracellular growth of drug-susceptible and drug-resistant strains of Mtb and
induced phagosome-lysosome fusion and autophagy in a SIRT1-dependent manner.
SIRT1 activation dampened Mtb-mediated persistent inflammatory responses via
deacetylation of RelA/p65, leading to impaired binding of RelA/p65 on the
promoter of inflammatory genes. In Mtb-infected mice, the use of SIRT1 activators
ameliorated lung pathology, reduced chronic inflammation, and enhanced efficacy
of anti-TB drug. Mass cytometry-based high-dimensional analysis revealed that
SIRT1 activation mediated modulation of lung myeloid cells in Mtb-infected mice.
Myeloid cell-specific SIRT1 knockout mice display increased inflammatory
responses and susceptibility to Mtb infection. Collectively, these results
provide a link between SIRT1 activation and TB pathogenesis and indicate a
potential of SIRT1 activators in designing an effective and clinically relevant
host-directed therapies for TB.
PMID- 28707005
TI - NMR Metabolomics in Ionizing Radiation.
PMID- 28707006
TI - Editorial.
AB - Dear colleagues, It is a pleasure to introduce you to the 2nd issue of UIO in
2017, demonstrating, again, the wide applications and promising developments in
ultrasonography. The issue starts with a special editorial from Ioan Sporea from
Romania, very well known for his scientific work on the clinical significance of
elastography. Dr. Sporea outlines the central role of modern sonographic
techniques for clinical decision making in modern hepatology. Together with the
great advances in the treatment of chronic viral hepatitis, ultrasonography with
elastography and CEUS as a "one stop shopping" facility may give us all the
information we need to proceed to treatment, thus superseding liver biopsy in
many (though definitively not all) patients with liver disease.
PMID- 28707007
TI - Wrinkle and crack-dependent charge transport in a uniaxially strained conducting
polymer film on a flexible substrate.
AB - We investigate charge transport in poly(3,4-ethylene dioxythiophene) polystyrene
sulfonate (PEDOT:PSS) films on functionalized polydimethylsiloxane (PDMS)
substrates under varying uniaxial strain up to 16%. Strong anisotropy in
transport is observed at a large applied strain (epsilon > 4%), which is
understood in terms of an extrinsic process, involving a change in density of
cracks from a few cracks per mm at epsilon = 4% to >100 cracks per mm at epsilon
= 16%. The quasi-periodic cracks are aligned perpendicular to the stretching
direction. A strain-history dependent response of the resistance of PEDOT:PSS
films cycled through a uniaxial strain up to 4% is also observed, for current
paths which are both parallel and perpendicular to the direction of stretching.
The resistance-strain plots of strained PEDOT:PSS films for the second and
subsequent few strain cycles follow the reverse path of the previous strain
cycle. This unique strain-history dependence of resistance helps to identify the
source of resistance changes at a low strain (epsilon < 4%). We demonstrate that
the out-of-plane uniaxial wrinkle arrays that appear in a direction parallel to
stretching have the same hysteresis response as the resistance, and therefore
wrinkle formation governs the low-strain resistance changes. These phenomena are
extensively investigated with dc-conductivity and frequency-dependent-ac
conductivity measurements, and surface morphological studies of the films under
various applied strains. Our work quantitatively identifies the contributions of
wrinkles and cracks to the change in resistance of PEDOT:PSS under an applied
strain.
PMID- 28707008
TI - Lifestyle differences between older migrants and non-migrants in 14 European
countries using propensity score matching method.
AB - OBJECTIVES: We examine the differences in lifestyle between four groups of
migrants-first generation of older migrants originating from one of the EU
countries, Africa or the Middle East and second-generation older EU migrants-with
non-migrants in their country of destination. METHODS: We use wave 5 of the SHARE
data. To control for differences in socio-demographic characteristics, cultural
factors and duration of stay in country of destination between migrants and non
migrants, we use propensity matching score analysis. RESULTS: Older migrants from
Southern European countries are more likely to smoke than non-migrants in their
country of origin. Older migrants originating from Africa and the Middle East are
more likely to smoke than non-migrants in their country of destination. Some
groups of second-generation older migrants are more likely to consume alcohol and
to have lower levels of physical activity than non-migrants in their country of
destination. CONCLUSIONS: Our results show that differences in lifestyle between
migrants and non-migrants exist, but they are not solely related to their migrant
status. Cultural and socio-demographic characteristics also play a role.
PMID- 28707009
TI - Differences in the risk of cardiovascular disease for movers and stayers in New
Zealand: a survival analysis.
AB - OBJECTIVES: To explore if risk of cardiovascular disease (CVD) for participants
who moved before their first CVD event is higher than for stayers, and examine
whether the relationship is moderated by ethnicity. METHODS: The sample comprised
2,068,360 New Zealand residents enrolled in any Primary Health Organisation, aged
between 30 and 84 years, had complete demographic information, and no prior
history of CVD. Cox proportional regression was used to compare CVD risk between
movers and stayers. The analysis was conducted for the whole sample and
stratified by ethnicity. RESULTS: The combined analysis suggested that movers
have a lower risk of CVD than stayers. This is consistent for all ethnic groups
with some variation according to experience of deprivation change following
residential mobility. CONCLUSIONS: Although mobile groups may have a higher risk
of CVD than immobile groups overall, risk of CVD in the period following a
residential mobility event is lower than for stayers. Results are indicative of a
short-term healthy migrant effect comparable to that observed for international
migrants.
PMID- 28707010
TI - [Liver resection for colorectal metastases in elderly patients].
PMID- 28707012
TI - Soluble form of transferrin receptor-1 level is associated with the age at first
diagnosis and the risk of therapeutic intervention and iron overloading in
patients with non-transfusion-dependent thalassemia.
AB - We retrospectively evaluated the relationship between serum transferrin receptor
1 (sTfR1) and some fundamental events in the life and the management (the age at
diagnosis, the age at the first red blood cells transfusion, the age at
splenectomy, and the overall need of chelation therapy) of 111 patients with non
transfusion-dependent thalassemia (NTDT) subdivided in four genetic entities:
patients with homozygous or compound heterozygous state for beta-thalassemia,
patients with triplicated alpha genotype associated with beta heterozygosity,
patients with deletional HbH, and patients with the combination of a beta defect
plus a beta chain variant. We found that the group with homozygous or compound
heterozygous state for beta-thalassemia had the highest sTfR1 levels and that the
presence of increased sTfR1 levels (>5 times normal) was associated with a
complex and severe history of disease requiring splenectomy, occasional red blood
cells transfusions, and early start and continuous iron chelation therapy.The
complexity in the management of NTDT patients is an emerging issue due to the
wide heterogeneity of clinical behavior. Our data indicate that the measurement
of sTfR1 levels, a common laboratory test, could contribute to correctly stratify
disease history and the iron chelation strategy in NTDT patients.
PMID- 28707013
TI - Sunitinib is effective and tolerable in Chinese patients with advanced pancreatic
neuroendocrine tumors: a multicenter retrospective study in China.
AB - PURPOSE: To determine the efficacy and safety of sunitinib in Chinese patients
with unresectable or metastatic pancreatic neuroendocrine tumors (pNETs) and the
clinical significance of steady-state sunitinib serum concentrations. METHODS: We
conducted a multicenter retrospective study including six centers from across
China. A total of 60 patients with unresectable or metastatic pNETs who were
treated with sunitinib were evaluated retrospectively. RESULTS: The median
overall survival (OS) was 47.5 months and the median time to progression (TTP)
was 15.3 months. The objective response rate was 5.0%, and the stable disease
(SD) rate was 81.7%. About 35.2% of patients required a dosage decrease from 37.5
to 25 mg/day due to adverse events, which in most cases were alleviated or
disappeared with the dosage reduction. In 14 patients who experienced sunitinib
related hypertension, 2 achieved a partial response (PR) and 11 had SD. The
median OS and TTP of these 14 patients experienced hypertension were both not
reached. The median Css of sunitinib was similar between patients treated with
sunitinib 37.5 and 25 mg/day (P = 0.955), but higher in patients who had PR than
in those who achieved SD or progressive disease, although no statistically
significant difference was found (P = 0.173). CONCLUSIONS: Sunitinib had similar
treatment efficacy to western patients with pNET in China. A 25 mg/day dosage was
better tolerated than 37.5 mg/day in Chinese patients, and there were no
significant differences in sunitinib Css between the two dosage groups. Patients
with higher sunitinib Css seem to have better efficacy. Sunitinib-related
hypertension may be a predictor of a better treatment effect.
PMID- 28707014
TI - Doxycycline and its quaternary ammonium derivative for adjuvant therapies of
chondrosarcoma.
AB - PURPOSE: This study was conducted during the development of innovative treatment
targeting the microenvironment of chondrosarcoma. In this context, MMP inhibitors
were conjugated with a quaternary ammonium (QA) function as a targeting ligand to
proteoglycans of chondrosarcoma extracellular matrix. Here we report the proof of
concept of this strategy applied to the MMP13 inhibitor, doxycycline (Dox).
METHODS: A quaternary ammonium derivative of the MMP13 inhibitor doxycycline (QA
Dox) was synthesized, and its anticancer activity was evaluated in the Swarm rat
chondrosarcoma (SRC) model compared with the parent drug doxycycline, in vitro
and in vivo. In vivo, dox and QA-Dox efficiency was assessed at equimolar doses
according to a q4dx4 schedule by monitoring tumour volume by MRI and PG-targeted
scintigraphy. Molecular mechanism (MMP13 expression, proteoglycan level) and
histology studies were performed on tumours. RESULTS: The link of QA targeting
function to Dox maintained the MMP13 inhibitory activity in vitro. Interestingly,
the bacteriostatic activity was lost. SRC cells incubated with both drugs were
blocked in S and G2 M phases. Tumour growth inhibition (confirmed by histology)
was observed for both Dox and QA-Dox. Undesirable blood effects (leukocyte
decrease) were reduced when Dox was targeted to tumour tissue using the QA
function. CONCLUSIONS: In the SRC model, the MMP13 inhibitor Dox and its QA
derivative are promising as adjuvant therapies for chondrosarcoma management.
PMID- 28707011
TI - Epithelial cell senescence: an adaptive response to pre-carcinogenic stresses?
AB - Senescence is a cell state occurring in vitro and in vivo after successive
replication cycles and/or upon exposition to various stressors. It is
characterized by a strong cell cycle arrest associated with several molecular,
metabolic and morphologic changes. The accumulation of senescent cells in tissues
and organs with time plays a role in organismal aging and in several age
associated disorders and pathologies. Moreover, several therapeutic interventions
are able to prematurely induce senescence. It is, therefore, tremendously
important to characterize in-depth, the mechanisms by which senescence is
induced, as well as the precise properties of senescent cells. For historical
reasons, senescence is often studied with fibroblast models. Other cell types,
however, much more relevant regarding the structure and function of vital organs
and/or regarding pathologies, are regrettably often neglected. In this article,
we will clarify what is known on senescence of epithelial cells and highlight
what distinguishes it from, and what makes it like, replicative senescence of
fibroblasts taken as a standard.
PMID- 28707015
TI - The Eating Assessment Tool-10 Predicts Aspiration in Adults with Stable Chronic
Obstructive Pulmonary Disease.
AB - Adults with COPD frequently present with dysphagia, which often leads to clinical
complications and hospital admissions. This study investigates the ability of the
Eating Assessment Tool (EAT-10) to predict aspiration during objective dysphagia
evaluation in adults with stable COPD. Thirty adults (20 male, 10 female; mean
age = 69.07 +/- 16.82) with stable COPD attended an outpatient dysphagia clinic
for a fiberoptic endoscopic evaluation of swallowing (FEES) in an acute teaching
hospital (January 2015-November 2016). During evaluations, individuals completed
an EAT-10 rating scale followed immediately by a standardised FEES exam.
Aspiration status during FEES was rated using the penetration-aspiration scale by
clinicians blinded to EAT-10 scores. Data were retrospectively analysed.
Significant differences in mean EAT-10 scores were found between aspirators
(16.3; SEM = 2.165) and non-aspirators (7.3; SEM = 1.009) (p = 0.000). The EAT-10
predicted aspiration with a high level of accuracy (AUC = 0.88). An EAT-10 cut
off value of >9 presented a sensitivity of 91.67, specificity of 77.78 with
positive and negative likelihood ratios of 4.12 and 0.11, respectively. Positive
and negative predictive values were 73.30 and 93.30, respectively. Diagnostic
odds ratio was 38.50 (p < 0.01, CI 3.75-395.42). EAT-10 is a quick, easy to
administer tool, which can accurately predict the presence of aspiration in
adults with COPD. The scale can also very accurately exclude the absence of
aspiration, helping clinicians to determine the need for onward referral for a
comprehensive dysphagia evaluation. This may ultimately reduce clinical
complications and hospital admissions resulting from dysphagia in this clinical
population.
PMID- 28707016
TI - Patterns of reoperation after failed fundoplication: an analysis of 9462
patients.
AB - BACKGROUND: Little is known about the choice of reoperation after failed
fundoplication for gastroesophageal reflux disease. Both redo fundoplication and
conversion procedure to Roux-en-Y gastric bypass (RYGB) are safe and effective.
We aimed to characterize the rates of different revisional procedures and to
identify risk factors associated with failed fundoplication. METHODS: Using a
statewide database, we examined records for patients who underwent fundoplication
between 2000 and 2010. The primary outcomes were the rate of each type of
reoperation and the pattern of subsequent procedures. Demographics and
comorbidities were used in a multivariable logistic regression model to identify
risk factors associated with reoperation after fundoplication. RESULTS: A total
of 9462 patients were included. Overall, 430 (4.5%) patients underwent
reoperation. Of those, 46 (10.7%) patients underwent RYGB at first reoperation,
with the remainder having a redo fundoplication. An additional five patients were
converted to RYGB after undergoing a redo fundoplication (51 total patients
converted to RYGB at any point, 11.9%). Eighty-three percent of patients
converted to RYGB were obese, as opposed to 8% for redo fundoplication. A single
redo fundoplication was done in 81% of patients, while 35 patients (8.1%)
underwent two or more revisional procedures. On average, any reoperation was
performed 2.9 years after fundoplication, with redo fundoplication 2.5 years and
RYGB 6.5 years later. Age 30-49 years (vs. >70 years; OR 2.01, p = 0.011) and 50
69 years (vs. >70 years; OR 1.61, p = 0.011), female gender (OR 1.56, p = <
0.0001), and chronic pulmonary disease (OR 1.40, p = 0.0044) were associated with
revisional surgery. CONCLUSIONS: Fundoplication has a low reoperation rate within
a mean 8.3 years of follow-up. Redo fundoplication is more commonly performed and
at an earlier point than conversion to RYGB. Younger age, female gender, and
chronic pulmonary disease are associated with reoperation after fundoplication.
PMID- 28707017
TI - Basic research and model systems in familial dysautonomia: What do we know and
what's next?
PMID- 28707018
TI - Postoperative Enterococcus faecalis endophthalmitis: virulence factors leading to
poor visual outcome.
AB - : Purpose Postoperative endophthalmitis caused by Enterococcus faecalis often
results in poor visual outcome due to retinal destruction. We evaluated the
virulence factors of Enterococcus faecalis clinical isolates and analyzed their
relationship with retinal destruction and poor visual outcomes in postoperative
bacterial endophthalmitis (PBE) following cataract surgery. STUDY DESIGN:
Retrospective. METHODS: E. faecalis isolates from nine acute-onset PBE cases were
examined using pulsed-field gel electrophoresis of genomic DNA, plasmid isolation
and pheromone response experiments. Virulence determinant genes, including
cytolysin (cylA), aggregation substance (asa1), enterococcal surface protein
(esp), gelatinase (gelE) and adhesin of collagen from enterococci (ace), were
examined by polymerase chain reaction. Expression of cytolysin and secreted
protease were also tested. Retinal findings observed during vitrectomy surgery
and final visual acuities were compared to obtained microbiological data. Poor
visual outcome was defined as final visual acuity of less than 0.1 (decimal).
RESULTS: Although nine isolates were collected, two were identical. Out of the
eight different isolates, three were positive for both expressions of cytolysin
and secreted proteases. Plasmid DNAs were isolated from six of eight isolates,
while pheromone response was observed in five isolates. The asa1, esp and ace
genes were positive in six, five and eight of the isolates, respectively.
Patients with retinal destruction exhibited significantly higher prevalence of
secreted protease expression versus those without (P < 0.05), and retinal
destruction was related to poor visual outcome (P < 0.05). CONCLUSIONS: Our data
suggest that enterococcal secreted proteases were correlated to retinal
destruction, thereby fostering poor visual outcomes in eyes with enterococcal
endophthalmitis.
PMID- 28707020
TI - ESCP International Workshop Extended responsibilities for pharmacists in the
treatment of acute and chronic conditions, 15-16 June 2017, Leiden, The
Netherlands.
PMID- 28707019
TI - [Medical examination: Preparation for ENT specialisation : Part 31].
PMID- 28707021
TI - The response to Trendelenburg position is minimally affected by underlying
hemodynamic conditions in patients with aortic stenosis.
AB - PURPOSE: Trendelenburg positioning is commonly used to temporarily treat
intraoperative hypotension. The Trendelenburg position improves cardiac output in
normovolemic or anesthetized patients, but not hypovolemic or non-anesthetized
patients. Therefore, the response to Trendelenburg positioning may vary depending
on patient population or hemodynamic conditions. We thus tested the hypothesis
that the effectiveness of the Trendelenburg position, as indicated by an increase
in cardiac output, improves after replacement of a stenotic aortic valve.
Secondarily, we evaluated whether measurements of left ventricular preload,
systolic function, or afterload were associated with the response to
Trendelenburg positioning. METHODS: This study is a secondary analysis of a
clinical trial which included patients having aortic valve replacement (AVR) who
were monitored with pulmonary artery catheters (NCT01187329). We examined changes
in thermodilution cardiac output with Trendelenburg positioning before and after
AVR. We also examined whether echocardiographic and hemodynamic measurements of
preload, afterload, and systolic function were associated with changes in cardiac
output during Trendelenburg positioning. RESULTS: Thirty-seven patients were
included. The median [IQR] cardiac output change with Trendelenburg positioning
was -3% [-10%, 5%] before AVR versus +4% [-4%, 15%] after AVR. Estimated median
difference in cardiac output with Trendelenburg was 5% (95% CI 1, 15%, P = 0.04)
greater after AVR. The response to Trendelenburg positioning was largely
independent of hemodynamic conditions. CONCLUSION: The response to Trendelenburg
positioning improved following AVR, but by a clinically unimportant amount. The
response to Trendelenburg positioning was independent of hemodynamic conditions.
PMID- 28707023
TI - Oxidative inactivation of the endogenous antioxidant protein DJ-1 by the food
contaminants 3-MCPD and 2-MCPD.
AB - 3-Chloro-1,2-propanediol (3-MCPD) and 2-chloro-1,3-propanediol (2-MCPD) are heat
induced food contaminants being present either as free substances or as fatty
acid esters in numerous foods. 3-MCPD was classified to be possibly carcinogenic
to humans (category 2B) with kidney and testis being the primary target organs
according to animal studies. A previous 28-day oral feeding study with rats
revealed that the endogenous antioxidant protein DJ-1 was strongly deregulated at
the protein level in kidney, liver, and testis of the experimental animals that
had been treated either with 3-MCPD, 2-MCPD or their dipalmitate esters. Here we
show that this deregulation is due to the oxidation of a conserved, redox-active
cysteine residue (Cys106) of DJ-1 to a cysteine sulfonic acid which is equivalent
to loss of function of DJ-1. Irreversible oxidation of DJ-1 is associated with a
number of oxidative stress-related diseases such as Parkinson, cancer, and type
II diabetes. It is assumed that 3-MCPD or 2-MCPD do not directly oxidize DJ-1,
but that these substances induce the formation of reactive oxygen species (ROS)
which in turn trigger DJ-1 oxidation. The implications of 3-MCPD/2-MCPD-mediated
ROS formation in vivo for the ongoing risk assessment of these compounds as well
as the potential of oxidized DJ-1 to serve as a novel effect biomarker for 3
MCPD/2-MCPD toxicity are being discussed.
PMID- 28707022
TI - TLDc proteins: new players in the oxidative stress response and neurological
disease.
AB - Oxidative stress (OS) arises from an imbalance in the cellular redox state, which
can lead to intracellular damage and ultimately cell death. OS occurs as a result
of normal ageing, but it is also implicated as a common etiological factor in
neurological disease; thus identifying novel proteins that modulate the OS
response may facilitate the design of new therapeutic approaches applicable to
many disorders. In this review, we describe the recent progress that has been
made using a range of genetic approaches to understand a family of proteins that
share the highly conserved TLDc domain. We highlight their shared ability to
prevent OS-related cell death and their unique functional characteristics, as
well as discussing their potential application as new neuroprotective factors.
Furthermore, with an increasing number of pathogenic mutations leading to
epilepsy and hearing loss being discovered in the TLDc protein TBC1D24,
understanding the function of this family has important implications for a range
of inherited neurological diseases.
PMID- 28707024
TI - Experience of Immediate Ambulation and Early Discharge After Tumescent Anesthesia
and Propofol Infusion in Cosmetic Breast Augmentation.
AB - INTRODUCTION: Current cosmetic breast augmentation relies on general anesthesia
that normally requires 40 min to total recovery. With experience, the surgical
procedure can be completed expediently in 20 min under tumescent anesthesia and
propofol full sedation to achieve immediate postoperative ambulation and home
discharge readiness, and thus improve patient satisfaction and reduce cost. We
retrospectively examined the outcomes of the protocol. MATERIALS AND METHODS: Per
protocol, 1200 female patients underwent simple cosmetic breast augmentation
accomplished with tumescent anesthesia, immediate mobilization, and early home
discharge readiness after surgery. The following records were analyzed: vital
sign stability during mobilization in the first 30 cases (primary goal), duration
of surgery and anesthesia, frequency of intraoperative opioid use, frequency of
ambulation needing assistance, Verbal Analog Scores and incidences of pain,
orthostatic intolerance events, incidences of postoperative nausea and vomiting
or anti-emetic use, and complications at follow-up visits (secondary goal).
RESULTS: Hemodynamics during immediate postoperative mobilization demonstrated no
statistically significant fluctuations and/or orthostatic intolerance requiring
interventions. The mean duration of surgery was 20.4 +/- 4.1 min. The mean
duration of anesthesia was 25.2 +/- 6.8 min. All patients tolerated immediate
postoperative ambulation well. Adverse postoperative events were scarce. Only
9.1% reported postoperative pain, and 5.7% reported postoperative nausea and
vomiting. One percent had transit post-ambulation dizziness needing supine
positioning for less than 3 min. The average time to meet home-readiness criteria
was 4.7 min, and there was no incidence of hematoma, infection, or complaints at
follow-ups. CONCLUSIONS: For simple cosmetic breast augmentation, instead of
general anesthesia and 40 min of recovery time, a tumescent anesthetic technique
can be used for immediate postoperative ambulation and a 4.7-min home discharge
readiness without a decrease in anesthesia quality and safety. LEVEL OF EVIDENCE
IV: This journal requires that authors assign a level of evidence to each
article. For a full description of these Evidence-Based Medicine ratings, please
refer to the Table of Contents or the online Instructions to Authors
www.springer.com/00266 .
PMID- 28707025
TI - Interest in Long-Acting Injectable PrEP in a Cohort of Men Who have Sex with Men
in China.
AB - Long-acting injectable (LAI) formulations of antiretrovirals (ARVs) as pre
exposure prophylaxis (PrEP) could be an attractive alternative for men who have
sex with men (MSM) who are interested in ARV-based biomedical prevention but will
not use a daily pill. This study investigated interest in LAI-PrEP in a cohort of
MSM in China and characterized how MSM willing to use only injectable PrEP
differed from MSM who would use PrEP regardless of modality or not at all.
Demographic, behavioral, and risk perception measures were collected and
associations investigated. A licensed LAI-PrEP agent would increase the
proportion interested in PrEP by 24.5% over oral PrEP alone. Combining interest
in oral and injectable PrEP, 78.5% of the sample could be covered if reported
interest in PrEP translated into actual uptake. Partnership factors
differentiated those who would be willing to use only LAI-PrEP versus any PrEP
modality, while higher self-perception of risk was associated with interest in
LAI-PrEP versus no PrEP. The addition of a second PrEP modality could yield
increased population coverage of PrEP. Social and behavioral research should be
undertaken in parallel with clinical development of injectable PrEP agents to
identify characteristics of those who are not interested in oral PrEP but would
take advantage of ARV-based prevention with the introduction of an injectable
product.
PMID- 28707026
TI - Association between BNP levels and new-onset atrial fibrillation : A propensity
score approach.
AB - BACKGROUND: New-onset atrial fibrillation (NOAF), a common complication of acute
ST-segment elevation myocardial infarction (STEMI), is associated with a poor
prognosis. Several clinical and laboratory parameters are reported to be
associated with NOAF in patients with STEMI. The aim of the present study was to
evaluate the predictive value of plasma B-type natriuretic peptide (BNP) levels
for NOAF development and long-term prognosis in STEMI patients undergoing primary
percutaneous coronary intervention (pPCI). PATIENTS AND METHODS: We
retrospectively enrolled 1,928 patients with STEMI who underwent pPCI. After
applying exclusion criteria, 1,057 patients were retained in the final study
population. Patients with NOAF were compared with patients without NOAF in the
entire study population and in a matched group. RESULTS: Patients with NOAF had a
significantly higher average plasma BNP level (161 pg/ml, range: 72.3-432) than
patients without NOAF in the study population (70.7 pg/ml, range: 70-129; p <
0.001) and in the matched group (104.6 pg/ml, range: 47.2-234.5; p = 0.014).
Furthermore, the plasma BNP level was found to be an independent predictor of
NOAF development (odds ratio [OR]: 1.003; 95% confidence interval [CI]: 1.000
1.005; p = 0.034) and mortality in the long-term follow-up (OR: 1.004; 95% CI:
1.002-1.006; p < 0.001). CONCLUSION: The present study found that a high plasma
BNP level was significantly associated with NOAF development in STEMI patients,
and was an independent predictor of NOAF development and all-cause mortality
during long-term follow-up, regardless of other NOAF risk factors.
PMID- 28707027
TI - Root-associated fungal communities in three Pyroleae species and their mycobiont
sharing with surrounding trees in subalpine coniferous forests on Mount Fuji,
Japan.
AB - Pyroleae species are perennial understory shrubs, many of which are partial
mycoheterotrophs. Most fungi colonizing Pyroleae roots are ectomycorrhizal (ECM)
and share common mycobionts with their Pyroleae hosts. However, such mycobiont
sharing has neither been examined in depth before nor has the interspecific
variation in sharing among Pyroleae species. Here, we examined root-associated
fungal communities in three co-existing Pyroleae species, including Pyrola
alpina, Pyrola incarnata, and Orthilia secunda, with reference to co-existing ECM
fungi on the surrounding trees in the same soil blocks in subalpine coniferous
forests. We identified 42, 75, and 18 fungal molecular operational taxonomic
units in P. alpina, P. incarnata, and O. secunda roots, respectively. Mycobiont
sharing with surrounding trees, which was defined as the occurrence of the same
mycobiont between Pyroleae and surrounding trees in each soil block, was most
frequent among P. incarnata (31 of 44 plants). In P. alpina, sharing was
confirmed in 12 of 37 plants, and the fungal community was similar to that of P.
incarnata. Mycobiont sharing was least common in O. secunda, found in only 5 of
32 plants. Root-associated fungi of O. secunda were dominated by Wilcoxina
species, which were absent from the surrounding ECM roots in the same soil
blocks. These results indicate that mycobiont sharing with surrounding trees does
not equally occur among Pyroleae plants, some of which may develop independent
mycorrhizal associations with ECM fungi, as suggested in O. secunda at our
research sites.
PMID- 28707028
TI - Involvement of aurantiactinomyxon in the life cycle of Thelohanellus testudineus
(Cnidaria: Myxosporea) from allogynogenetic gibel carp Carassius auratus gibelio,
with morphological, ultrastructural, and molecular analysis.
AB - During the investigation of actinosporean fauna diversity from commercial fish
ponds in Hubei Province, China, a novel aurantiactinomyxon type was found from
Branchiura sowerbyi. Spore body of the aurantiactinomyxon was ellipsoidal in side
view and triangular in apical view, 15.5 +/- 0.5 (14.5-16.4) MUm in diameter;
three leaf-like caudal processes were approximately equal, measuring 13.2 +/- 0.9
(11.5-16.2) MUm long and 7.4 +/- 0.4 (6.7-8.0) MUm wide at the base; three polar
capsules were located at the apex of spore body, globular in apical view, 2.2 +/-
0.1 (2.0-2.3) MUm in diameter, and pyriform in side view, 2.5 +/- 0.2 (2.3-2.9)
MUm in length and 2.0 +/- 0.2 (1.8-2.4) MUm in width; a total of 32 germ cells
were observed within the sporoplasm. Ultrastructural analysis showed that the
development was asynchronous between pansporocysts but synchronous within a
pansporocyst. The formation of sporoblast and the development of sporogonic stage
were also described and discussed. The 18S ribosomal DNA sequences of the current
aurantiactinomyxon type corresponded to that of a previously reported
Thelohanellus testudineus, suggesting that the newly identified
aurantiactinomyxon type is the actinosporean stage in the life cycle of T.
testudineus.
PMID- 28707029
TI - [Traumatized relatives of intensive care patients].
AB - Relatives are not only visitors in the intensive care unit, but provide support
and care for patients at the end of life, and serve as an important source of
information for clinicians. They are confronted, often unexpectedly and
unprepared, with life-threatening illness, death and dying and life-threatening
decisions to limit therapy. Thus, they are often substantially burdened
themselves and are in need of support. It is undisputed that communication with
relatives can have an adaptive or also traumatic influence on the experience
gained.
PMID- 28707030
TI - [Update: acute hypercapnic respiratory failure].
AB - BACKGROUND: Hypercapnic respiratory failure is a frequent problem in critical
care and mainly affects patients with acute exacerbation of COPD (AECOPD) and
acute respiratory distress syndrome (ARDS). In recent years, the usage of
extracorporeal CO2 removal (ECCO2R) has been increasing. OBJECTIVE: Summarizing
the state of the art in the management of hypercapnic respiratory failure with
special regard to the role of ECCO2R. METHODS: Review based on a selective
literature search and the clinical and scientific experience of the authors.
RESULTS: Noninvasive ventilation (NIV) is the therapy of choice in hypercapnic
respiratory failure due to AECOPD, enabling stabilization in the majority of
cases and generally improving prognosis. Patients in whom NIV fails have an
increased mortality. In these patients, ECCO2R may be sufficient to avoid
intubation or to shorten time on invasive ventilation; however, corresponding
evidence is sparse or even missing when it comes to hard endpoints. Lung
protective ventilation according to the ARDS network is the standard therapy of
ARDS. In severe ARDS, low tidal volume ventilation may result in critical
hypercapnia. ECCO2R facilitates compensation of respiratory acidosis even under
"ultra-protective" ventilator settings. Yet, no positive prognostic effects could
be demonstrated so far. CONCLUSION: Optimized use of NIV and lung-protective
ventilation remains standard of care in the management of hypercapnic respiratory
failure. Currently, ECCO2R has to be considered an experimental approach, which
should only be provided by experienced centers or in the context of clinical
trials.
PMID- 28707031
TI - Silencing of P2X7R by RNA interference in the hippocampus can attenuate
morphological and behavioral impact of pilocarpine-induced epilepsy.
AB - Cell signaling mediated by P2X7 receptors (P2X7R) has been suggested to be
involved in epileptogenesis, via modulation of intracellular calcium levels,
excitotoxicity, activation of inflammatory cascades, and cell death, among other
mechanisms. These processes have been described to be involved in pilocarpine
induced status epilepticus (SE) and contribute to hyperexcitability, resulting in
spontaneous and recurrent seizures. Here, we aimed to investigate the role of
P2X7R in epileptogenesis in vivo using RNA interference (RNAi) to inhibit the
expression of this receptor. Small interfering RNA (siRNA) targeting P2X7R mRNA
was injected into the lateral ventricles (icv) 6 h after SE. Four groups were
studied: Saline-Vehicle, Saline-siRNA, Pilo-Vehicle, and Pilo-siRNA. P2X7R was
quantified by western blotting and neuronal death assessed by Fluoro-Jade B
histochemistry. The hippocampal volume (edema) was determined 48 h following
RNAi. Behavioral parameters as latency to the appearance of spontaneous seizures
and the number of seizures were determined until 60 days after the SE onset. The
Saline-siRNA and Pilo-siRNA groups showed a 43 and 37% reduction, respectively,
in P2X7R protein levels compared to respective vehicle groups. Neuroprotection
was observed in CA1 and CA3 of the Pilo-siRNA group compared to Pilo-Vehicle.
P2X7R silencing in pilocarpine group reversed the increase in the edema detected
in the hilus, suprapyramidal dentate gyrus, CA1, and CA3; reduced mortality rate
following SE; increased the time to onset of spontaneous seizure; and reduced the
number of seizures, when compared to the Pilo-Vehicle group. Therefore, our data
highlights the potential of P2X7R as a therapeutic target for the adjunct
treatment of epilepsy.
PMID- 28707032
TI - Receptor heterogeneity in optical biosensors.
AB - Scientists measure rate constants associated with biochemical reactions in an
optical biosensor-an instrument in which ligand molecules are convected through a
flow cell over a surface to which receptors are immobilized. We quantify
transport effects on such reactions by modeling the associated convection
diffusion equation with a reaction boundary condition. In experimental
situations, the full PDE model reduces to a set of unwieldy integrodifferential
equations (IDEs). Employing common physical assumptions, we may reduce the system
to an ODE model, which is more useful in practice, and which can be easily
adapted to the inverse problem of finding rate constants. The results from the
ODE model compare favorably with numerical simulations of the IDEs, even outside
its range of validity.
PMID- 28707033
TI - Impact of constant versus fluctuating temperatures on the development and life
history parameters of Tetranychus urticae (Acari: Tetranychidae).
AB - The impact of daily temperature fluctuations on arthropod life history parameters
is inadequately studied compared with the ample amount of research that has been
conducted on the effects of constant temperatures. Fluctuating temperatures are
likely to be more realistic, as they are ecologically more similar to what these
arthropods experience in nature. Here, we compared the impact of 11 constant
temperatures that ranged from 10 to 35 degrees C with fluctuating temperatures
with the same corresponding mean temperature and an amplitude of 10 degrees C
between high (12 h) and low (12 h) temperatures on the development and life
history parameters of Tetranychus urticae under continuous light conditions. No
eggs hatched at constant 10 degrees C, whereas 81.5% of eggs successfully
completed development at fluctuating 10 degrees C (15/5 degrees C). Egg-to
female adult development was faster under fluctuating temperatures from 12.5 to
27.5 degrees C than under constant temperatures, whereas the opposite trend was
observed at >30 degrees C. The lower thermal thresholds (T) were 11.63 and 8.63
degrees C, and thermal constants (K) were 127.81 and 150.69 degree-days for egg
to-female adults at constant and fluctuating temperatures, respectively. The
numbers of oviposition days were significantly higher at fluctuating 15 degrees
C than at the corresponding constant temperature, whereas the opposite trend was
observed from 20 to 30 degrees C. The intrinsic rate of increase (r) was higher
at fluctuating than at constant 15 degrees C. The net reproductive rate (R 0)
was also higher at fluctuating than at constant 15 and 35 degrees C, but showed
an opposite trend at 20 and 25 degrees C. We conclude that fluctuating
temperatures should be considered to accurately predict spider mite population
dynamics in nature.
PMID- 28707034
TI - Randomized controlled trial comparing Nd:YAG laser photocoagulation and bipolar
electrocautery in the management of epistaxis.
AB - The objective of this study is to evaluate the efficacy and degree of comfort of
Nd:YAG laser photocoagulation compared to bipolar electrocautery in the
management of epistaxis. Seventy-two consecutive patients with a history of
epistaxis were randomly assigned to receive treatment in an outpatient setting
consisting of either bipolar electrocautery (group 1) or Nd:YAG laser
photocoagulation (group 2). The study was conducted in university-affiliated
teaching hospital. Seventy-two consecutive patients who suffered from anterior
epistaxis and presented to the Otolaryngology Department at the Eye, Ear, Nose
and Throat Hospital, Fudan University, between June 2015 and August 2015. The
following outcome measures were assessed: bleeding intensity, bleeding frequency
4 and 16 weeks after treatment (0 = no bleeding, 1 = reduced bleeding, 2 = the
same, and 3 = worse), participant perception of discomfort during treatment
(grade 0-10, where 10 is the worst pain), and therapy duration and complications.
At 16 weeks, 91% of the laser patients versus 91% of the bipolar electrocautery
patients had no reported bleeding. The outcome scores at 4 and 16 weeks after
treatment showed no significant difference between the two groups (P = 0.5 and P
= 0.98, respectively; P > 0.05). The median pain levels experienced during the
office laser and bipolar electrocautery procedures were 3.0 and 4.0,
respectively, and the median durations of the laser and electrocautery therapies
were 3.0 and 4.0, respectively. Neither groups had complications. It can be
concluded that Nd:YAG laser photocoagulation and bipolar electrocautery are both
effective in the treatment of epistaxis. These two therapies are recommended. As
a whole, these two therapies, performed in an office setting, are timely,
efficacious, and well tolerated in the treatment of epistaxis.
PMID- 28707035
TI - Cerebellar ataxia and obstructive hydrocephalus, rare neurologic presentations in
patients with systemic lupus erythematosus.
AB - The first cases of systemic lupus erythematosus (SLE) with effects on the nervous
system were reported more than 100 years ago. Cerebellar involvement and
obstructive hydrocephalus are rarely encountered in patients with SLE. We report
two patients with SLE who developed cerebellar ataxia. The first patient
presented with significant headache at time of SLE diagnosis and negative brain
imaging studies on initial evaluation. The headache recurred with findings of
cerebellar ataxia and obstructive hydrocephalus. The patient's symptoms markedly
improved with shunt insertion and immunosuppressive therapies. The second
patient, known to have SLE, presented with crossed hemiplegia and cerebellar
symptoms. Imaging studies showed cerebellar atrophy as well as thalamic and
brainstem lesions. The patient had partial improvement with immunosuppression. To
understand the impact of SLE on the cerebellum and in hydrocephalus formation, we
reviewed the literature and case reports over the last 50 years. Clinical
presentations, laboratory results, imaging results, treatment and outcomes, for
reported cases found in the literature, were summarized and discussed along with
our conclusions. We emphasize the importance of history, examination and close
monitoring of patients with SLE presenting with headache or any new neurological
symptoms.
PMID- 28707036
TI - Treatment strategies for rectal cancer with synchronous liver metastases:
surgical and oncological outcomes with propensity-score analysis.
AB - BACKGROUND: The optimal sequence of surgery for rectal cancer (RC) with
synchronous liver metastases (SLM) is controversial. OBJECTIVES: The primary
objective was to explore differences between the rectum first (RF) and the liver
first strategy (LF) to achieve the complete resection (CR) of both tumors.
METHODS: Patients diagnosed of RC with resectable or potentially resectable SLM
were included. Data collected prospectively were analyzed with an intention-to
treat perspective, adjusting for between-sample differences (propensity score).
The complete resection rate (CRR) was the main outcome variable. RESULTS: During
a 5-year period, 23 patients underwent the LF strategy and 24 patients the RF
strategy. Median overall survival (OS) was 32 months in the LF group and 41
months in the RF group (p = 0.499), and was 51 and 17 months, respectively, for
patients achieving or not achieving CR of both tumors (p < 0.001). CRR's were 65%
in liver first group and 63% in rectum first group, (p = 0.846). No between
strategy differences in morbidity or duration of treatment were observed.
CONCLUSIONS: This study supports the notion that the achievement of CR of RC and
SLM should be the goal of oncological treatment. Both RF and LF strategies are
feasible and safe, but no between-strategy differences have been found in the
CRR.
PMID- 28707037
TI - Variability of composition and effects of essential oils from Rhanterium
adpressum Coss. & Durieu against mycotoxinogenic Fusarium strains.
AB - The antifungal potency of the essential oils of Rhanterium adpressum was
evaluated against four mycotoxigenic strains of the genus Fusarium. The essential
oils were obtained, separately, by hydro-distillation of the aerial parts of R.
adpressum (leaves and flowers). The parts were collected during the period of
bloom (3 months) for 3 years. The GC-MS analysis revealed thirty-six compounds
for the essential oils, divided into four classes of chemical compounds, with
variable percentages according to the month of extraction. The monoterpene
hydrocarbons form the main class in these oils. On the other hand, the highest
percentages of the oxygenated compounds are observed in the samples collected
during the month of May. The direct contact method was used to evaluate the
antifungal activity of the essential oils. The activity can be attributed to
their relatively high composition of oxygenated monoterpenes. Flowers extract
showed strong inhibitory activity, with very interesting concentrations of IC50
and MIC for both tests on solid and liquid medium. The effect of these oils on
the production of type B trichothecenes (TCTBs) was evaluated, showing a
significant inhibitory effect on TCTBs production, for both extracts (leaves and
flowers). The rates of inhibition were 66-97 and 76-100% of FX, 3-ADON and 15
ADON, respectively. The inhibition of fungal biomass and the production of TCTBs
depended on the used concentration of the essential oils. These results suggest
that the essential oils from R. adpressum are able to control the growth of the
tested strains and their subsequent production of TCTB mycotoxins.
PMID- 28707038
TI - [68Ga]PSMA-HBED-CC Uptake in Osteolytic, Osteoblastic, and Bone Marrow Metastases
of Prostate Cancer Patients.
AB - PURPOSE: The aim of this study was to evaluate potential differences in "Glu-NH
CO-NH-Lys" radio-labeled with [68Ga]gallium N,N-bis[2-hydroxy-5
(carboxyethyl)benzyl]ethylenediamine-N,N-diacetic acid ([68Ga]PSMA-HBED-CC)
uptake in osteolytic, osteoblastic, mixed, and bone marrow metastases in prostate
cancer (PC) patients. PROCEDURES: This retrospective study was approved by the
local ethics committee. Patients who received [68Ga]PSMA-HBED-CC positron
emission tomography/computed tomography ([68Ga]PSMA-PET/CT) with at least one
positive bone metastasis were included in this study. Only patients who have not
received systemic therapy for their PC were included. Bone metastases had to be
confirmed by at least one other imaging modality or follow-up investigation. The
maximum standardized uptake value (SUVmax) and mean Hounsfield units (HUmean) of
each metastasis were measured. Based on CT, each metastasis was classified as
osteolytic (OL), osteoblastic (OB), bone marrow (BM), or mixed (M). RESULTS: One
hundred fifty-four bone metastases in 30 patients were evaluated. Eighty out of
154 (51.9%) metastases were classified as OB, 21/154 (13.6%) as OL, 23/154
(14.9%) as M, and 30/154 (19.5%) as BM. The SUVmax for the different types of
metastases were 10.6 +/- 7.07 (OB), 24.0 +/- 19.3 (OL), 16.0 +/- 21.0 (M), and
14.7 +/- 9.9 (BM). The SUVmax of OB vs. OL and OB vs. BM metastases differed
significantly (p <= 0.025). A significant negative correlation between HUmean and
SUVmax (r = -0.23, p < 0.05) was measured. CONCLUSIONS: [68Ga]PSMA-HBED-CC uptake
is higher in osteolytic and bone marrow metastases compared to osteoblastic
metastases. Information derived from [68Ga]PSMA-PET and CT complement each other
for the reliable diagnosis of the different types of bone metastases in PC
patients.
PMID- 28707039
TI - Moving on: transitioning young people with chronic kidney disease to adult care.
AB - Advances in the care of children mean that adolescents with chronic kidney
disease (CKD) are surviving to adulthood and requiring transition to adult care.
The transition phase is well-recognised to be associated with considerable excess
morbidity and graft loss, but these outcomes may be avoidable through a
structured transition programme. This review will discuss the (1) challenges
encountered by patients with CKD, caregivers and clinicians during transition;
(2) predictors and outcomes of transition; (3) current guidelines on transition
from paediatric to adult renal services; (4) interventions and research
directions that may help to improve the care and outcomes for young people with
CKD in transition. In spite of the substantial improvement in health gains
required for this disadvantaged population, there is to date only limited
evidence on the effects of current transition programmes.
PMID- 28707040
TI - Non-invasive remote ischemic postconditioning stimulates neurogenesis during the
recovery phase after cerebral ischemia.
AB - Ischemic postconditioning (IPostC) has been reported to have neuroprotection
against ischemic diseases, and one cycle of IPostC induces neurogenesis when
treated nearby. To expanding these effects, we explored the effects of
repetitively remote IPostC (NRIPostC) on neurogenesis in the subgranular zone
(SGZ) and subentricular zone (SVZ) during stroke recovery. Animals underwent
transient cerebral ischemia were treated with vehicle or NRIPostC immediately
after reperfusion. Neurological severity scores, infarct size, neurogenesis, and
protein expression levels of nestin and GFAP were quantified at 3d, 7d, 14d, 21d
and 28d post-ischemia. Results showed that NRIPostC significantly reduced acute
infarction and improved neurological outcomes during the recovery phase.
Meanwhile, NRIPostC significantly increased the number of BrdU+/nestin+ cells in
SGZ on day 14 and in the SVZ on days 3, 7 and 14 respectively, and the number of
DCX+ cells from days 3 to 14. There were significant increments in the number of
BrdU+/NeuN+ and BrdU+/GFAP+ cells in the SGZ and SVZ during the stroke recovery.
The changing tendency of the protein expression of nestin and GFAP in DG was
consistent with the result mentioned above. In conclusion, NRIPostC reduced acute
infarction and improved functional outcomes up to 28d, and it induced
neurogenesis both in the SGZ and SVZ.
PMID- 28707041
TI - On the ratio of intercellular to ambient CO2 (c i/c a) derived from ecosystem
flux.
AB - The ratio of intercellular to ambient CO2 concentrations (c i/c a) plays a key
role in ecophysiology, micrometeorology, and global climatic change. However,
systematic investigation on c i/c a variation and its determinants are rare.
Here, the c i/c a was derived from measuring ecosystem fluxes in an even-aged
monoculture of rubber trees (Hevea brasiliensis). We tested whether c i/c a is
constant across environmental gradients and if not, which dominant factors
control c i/c a variations. Evidence indicates that c i/c a is not a constant.
The c i/c a exhibits a clear "V"-shaped diurnal pattern and varies across the
environmental gradient. Water vapor pressure deficit (D) is the dominant factor
controls over the c i/c a variations. c i/c a consistently decreases with
increasing D. c i/c a decreases with square root of D as predicted by the optimal
stomatal model. The D-driving single-variable model could simulate c i/c a as
well as that of sophisticated model. Many variables function on longer timescales
than a daily cycle, such as soil water content, could improve c i/c a model
prediction ability. Ecosystem flux can be effectively used to calculate c i/c a
and use it to better understand various natural cycles.
PMID- 28707042
TI - Validity of neoadjuvant chemotherapy with docetaxel, cisplatin, and S-1 for
resectable locally advanced gastric cancer.
AB - Gastrectomy with D2 lymphadenectomy plus postoperative chemotherapy is the
standard treatment for resectable locally advanced gastric cancer in Japan.
However, the prognosis of patients with serosa-positive tumors remains
unsatisfactory because of peritoneal recurrence. This study aimed to investigate
the validity of neoadjuvant therapy with docetaxel, cisplatin, and S-1 (DCS) in
patients with locally advanced gastric cancer. Thirty patients with locally
advanced gastric cancer underwent neoadjuvant DCS therapy at Dokkyo Medical
University Hospital between June 2013 and October 2015. Gastrectomy and D2
lymphadenectomy were performed after two cycles of preoperative DCS therapy. The
clinical responses of the primary gastric tumors based on endoscopic findings
were partial response in 17 patients (57%) and stable disease in 13 patients
(43%). Analysis of pathological response in the primary gastric lesions showed
grade 1a in five patients (17%), grade 1b in nine patients (30%), grade 2 in 11
patients (37%), and grade 3 in five patients (17%). Twenty-four patients (80%)
remained alive after a median follow-up period of 31 months. The 2- and 3-year
overall survival rates in all patients were 89 and 70%, respectively. The 2-year
overall survival rate in pathological responders (grade 1b-3) was 96%, compared
with 50% in pathological non-responders (grade 1a) (P = 0.00187). Pathological
responders had a significantly higher survival rate than non-responders. These
results indicate that neoadjuvant DCS therapy may improve the prognosis in
patients with serosa-positive locally advanced gastric cancer.
PMID- 28707043
TI - Leadless Pacing: Current State and Future Direction.
AB - Leadless pacing is now an established alternative to conventional pacing with
subcutaneous pocket and transvenous lead for patients with class I or II single
chamber pacing indication. Available 12-month follow-up data shows a 48% fewer
major complication rate in patients with MicraTM compared to a historical control
group in a nonrandomized study [1]. There is one system with Food and Drug
Administration (FDA) approval and two with the Communaute Europeenne (CE) mark.
The OPS code for the implantation is 8-83d.3 and the procedure has recently been
rated as a "new Examination and Treatment Method (NUB)" in the German DRG system,
meaning adequate reimbursement is negotiable with health insurance providers. The
systems offer similar generator longevity and programming possibilities as
conventional pacemaker systems, including rate response, remote monitoring, and
MRI safety. The biggest downsides to date are limitations to single-chamber
stimulation, lack of long-time data, and concerns of handling of the system at
the end of its life span. However, implant procedure complication rates and
procedure times do not exceed conventional pacemaker operations, and proper
training and patient selection is provided.
PMID- 28707044
TI - Seasonal Bushmeat Hunger in the Congo Basin.
AB - Unlike the Sudano-sahelian regions, which are confronted to severe periods of
food shortage, tropical rainforests are known to provide a constant supply of a
great diversity of food resources that mitigates the risk of food starvation for
omnivorous humans. Nevertheless, several African forest ethnic groups suffer from
a seasonal hunger induced by depletion in the procurement of bushmeat, which is a
food of paramount importance. Although the diet remains well balanced and meets
all the nutritional needs, the bushmeat cravers loose weight and experience a
stress that affects their well-being. Bushmeat hunger is a psychocultural form of
hunger that generates several mental disorders. We present results from
nutritional anthropology studies carried out among various Congo Basin forest
peoples, which regularly suffer from bushmeat hunger. We expose the physiological
risks that result from this psychological unrest, we argue that this type of
unsatisfied compiling desire for meat should be considered as a factor of food
insecurity and we conclude on its incidence on bushmeat trade. The immoderate
craving for bushmeat compromises the attempts to replace bushmeat by other
sources of meat and is a persisting obstacle to conservation initiatives that
fail to take the psychocultural values of bushmeat into consideration.
PMID- 28707045
TI - Management of Extraocular Infections.
AB - Extraocular infection is a frequently encountered problem in children including
neonates and infants. Prompt recognition of the extraocular disease and
management at first contact reduces the ocular morbidity and visual impairment.
Delay in administering appropriate therapy and referral to an eye care personnel
may result in blindness; sometimes bilateral, due to severe ophthalmia
neonatorum. This review is mainly aimed at offering basic, brief information
about common extraocular infections prevalent among infants and children living
in developing countries as a ready reference to practising pediatricians and
neonatologists. Through this review, the pediatricians, as the first contact may
feel confident and comfortable in managing ocular infection in pediatric
population particularly living in remote rural and tribal region. Literature
search was made by retrieving related publications through peer reviewed
journals, PUBMED and Cochrane meta-analysis.
PMID- 28707046
TI - Understanding the post-surgical bariatric experiences of patients two or more
years after surgery.
AB - BACKGROUND: In Canada, one year after bariatric surgery follow-up appointments
become less frequent and surgical recipients must cope with weight management
more independently. Up to 50% of patients experience weight regain by two years
post-surgery. Understanding the lived experiences of those who have gone through
the bariatric process may shed light on what is needed to support others moving
forward. Therefore, the purpose of the study was to gain an understanding of the
physical, psychological, social, and clinic-related experiences of individuals
who have undergone bariatric surgery at least two years prior. PURPOSE: The
purpose of the study was to gain an understanding of the physical, psychological,
social, and clinic-related experiences of individuals who have undergone
bariatric surgery at least two years prior. METHODS: In-depth, individual semi
structured interviews lasting approximately 60 min were conducted. Interviews
were transcribed verbatim and inductive content analysis was used to identify
emerging themes. Methods were employed throughout to support data
trustworthiness. RESULTS: Participants (n = 28; 21 female) were primarily middle
aged (mean: 49.7 +/- 12.7 years old), Caucasian (71%), and completed bariatric
surgery more than three years. The data fell naturally into four primary themes,
namely physical changes and challenges, psychological experiences, social
functioning and support, and clinic-related experiences and reflections.
CONCLUSIONS: Generally, participants described positive improvements in their
physical, psychological, and social state since surgery. However, concerns
pertaining to several unanticipated outcomes of the surgery were underscored and
informed the recommendations for other patients to be prepared to relearn about
ones' body, utilize the support services available, and be aware that social
relationships may change and/or require tending. Participants' insights can be
used to help others meet with long-term success post-bariatric surgery.
PMID- 28707047
TI - The quality of life of older people aging in place: a literature review.
AB - PURPOSE: In order to cope with the challenges that are the result of an aging
population, policies and services promote keeping elders in the community and
letting them age in place rather than sending them to specialized institutions.
Aging in place refers to the option where people can stay in their homes as they
age. This policy option, however, poses various challenges and may also threaten
the quality of life of the aging. A literature review was performed on the
quality of life of older people aging in place to determine whether the actual
assessment of quality of life can be used within aging in place. METHODS: Web of
Science, PubMed, CINAHL, Sociological Abstracts and Social Science Research
Network were searched for publications on "Ag(e)ing in place" AND "Quality of
life." RESULTS: Although assessment is crucial to a policy pursuing a good
quality of life, literature reveals that it is seldom performed. Only a small
part of the studies report on the assessment of quality of life, including the
instruments used and the results. The findings also indicate that there is no
consensus on the definition of quality of life or its domains structures.
CONCLUSION: As no existing instrument assessing the quality of life of older
people aging in place could be identified, such a tool should be developed,
because any policy towards this growing group of people should be complemented by
an evaluation.
PMID- 28707048
TI - Psychometric evaluation of an item bank for computerized adaptive testing of the
EORTC QLQ-C30 cognitive functioning dimension in cancer patients.
AB - BACKGROUND: The European Organisation of Research and Treatment of Cancer (EORTC)
Quality of Life Group is developing computerized adaptive testing (CAT) versions
of all EORTC Quality of Life Questionnaire (QLQ-C30) scales with the aim to
enhance measurement precision. Here we present the results on the field-testing
and psychometric evaluation of the item bank for cognitive functioning (CF).
METHODS: In previous phases (I-III), 44 candidate items were developed measuring
CF in cancer patients. In phase IV, these items were psychometrically evaluated
in a large sample of international cancer patients. This evaluation included an
assessment of dimensionality, fit to the item response theory (IRT) model,
differential item functioning (DIF), and measurement properties. RESULTS: A total
of 1030 cancer patients completed the 44 candidate items on CF. Of these, 34
items could be included in a unidimensional IRT model, showing an acceptable fit.
Although several items showed DIF, these had a negligible impact on CF
estimation. Measurement precision of the item bank was much higher than the two
original QLQ-C30 CF items alone, across the whole continuum. Moreover, CAT
measurement may on average reduce study sample sizes with about 35-40% compared
to the original QLQ-C30 CF scale, without loss of power. CONCLUSION: A CF item
bank for CAT measurement consisting of 34 items was established, applicable to
various cancer patients across countries. This CAT measurement system will
facilitate precise and efficient assessment of HRQOL of cancer patients, without
loss of comparability of results.
PMID- 28707049
TI - Locking screw-plate interface stability in carbon-fibre reinforced
polyetheretherketone proximal humerus plates.
AB - PURPOSE: Carbon-fibre reinforced polyetheretherketone (CFR-PEEK) plates have
recently been introduced for proximal humerus fracture treatment. The purpose of
this study was to compare the locking screw-plate interface stability in CFR-PEEK
versus stainless steel (SS) proximal humerus plates. METHODS: Locking screw
mechanical stability was evaluated independently in proximal and shaft plate
holes. Stiffness and load to failure were tested for three conditions: (1) on
axis locking screw insertion in CFR-PEEK versus SS plates, (2) on-axis locking
screw insertion, removal, and reinsertion in CFR-PEEK plates, and (3) 10-degree
off-axis locking screw insertion in CFR-PEEK plates. Cantilever bending at a rate
of 1 mm/minute was produced by an Instron machine and load-displacement data
recorded. RESULTS: Shaft locking screw load to failure was significantly greater
in CFR-PEEK plates compared to SS plates (746.4 +/- 89.7 N versus 596.5 +/- 32.6
N, p < 0.001). The stiffness and load to failure of shaft locking screws was
significantly decreased when inserted 10 degrees off-axis compared to on-axis in
CFR-PEEK plates (p < 0.001). Stiffness and load to failure did not vary
significantly following screw reinsertion in CFR-PEEK plates. CONCLUSION: The
mechanical stability of locking screws in CFR-PEEK plates is comparable or
superior to locking screws in SS plates.
PMID- 28707050
TI - Tensile strength of the pullout repair technique for the medial meniscus
posterior root tear: a porcine study.
AB - PURPOSE: The purpose of this study was to compare the load-to-failure of
different common suturing techniques with a new technique for the medial meniscus
posterior root tear (MMPRT). METHODS: Thirty porcine medial menisci were randomly
assigned to three suturing techniques used for transtibial pullout repair of the
MMPRT (n = 10 per group). Three different meniscal suture configurations were
studied: the two simple suture (TSS) technique, the conventional modified Mason
Allen suture (MMA) technique, and the new MMA technique using the FasT-Fix
combined with the Ultrabraid (F-MMA). The ultimate failure load was tested using
a tensile testing machine. RESULTS: The MMA and F-MMA groups demonstrated
significantly higher failure loads than the TSS group (P = 0.0003 and P = 0.0005,
respectively). No significant differences were observed between the MMA and F-MMA
groups (P = 0.734). CONCLUSIONS: The ultimate failure load was significantly
greater in the F-MMA than the TSS group and similar to the conventional MMA
technique.
PMID- 28707051
TI - Application of Transgalactosylation Activity of beta-Galactosidase from
Kluyveromyces lactis for the Synthesis of Ascorbic Acid Galactoside.
AB - In view of a commonly known beneficial role and low stability of ascorbic acid,
many efforts are constantly undertaken to produce its improved derivatives. This
paper presents results on the synthesis of ascorbic acid galactoside using
transgalactosylation properties of beta-galactosidase from Kluyveromyces lactis
and lactose as a donor of galactosyl moiety. The purpose of this study was to
determine the influence of selected factors (concentration and molar ratio of
substrates, amount of the enzyme preparation, pH of the solution, presence of
different ions) on the course of transgalactosylation reaction. Research has
shown that approx. 2.5% dry matter (d.m.; 12.7 g/L) of ascorbic acid galactoside
is formed under favourable conditions (50% (w/v) substrates, sodium ascorbate and
lactose at the molar ratio of 1.9:1, enzyme dose of 28,600 U/100 g lactose, pH =
7.0). The addition of Mg2+ or K+ ions to the reaction medium caused an increase
in the final product content (even up to approx. 3.4% d.m., 17.2 g/L), while Na+
or Mn2+ had an adverse impact on the yield. The gathered data may be valuable for
cosmetic or food industry.
PMID- 28707052
TI - Steered Molecular Dynamics for Investigating the Interactions Between Insulin
Receptor Tyrosine Kinase (IRK) and Variants of Protein Tyrosine Phosphatase 1B
(PTP1B).
AB - The aim of this study is to use steered molecular dynamics to investigate the
dissociation process between IRK and PTP1Bs for wild type and five mutants
(consisting of p.D181E, p.D181A, p.Q262A, p.D181A-Y46F, and p.D181A-Q262A). The
gained results are observed not only the unbinding mechanism of IRK-PTP1B
complexes came from pulling force profile, number of hydrogen bonds, and
interaction energy between IRK and PTP1Bs but also described PTP1B's point
mutations could variably change its binding affinity towards IRK. Additionally,
the binding free energy calculated by Molecular Mechanics/Poisson-Boltzmann
Surface Area (MM-PBSA) is also revealed that electrostatic energy and polar
solvation energy mainly made up the binding free energy of PTP1B-IRK complexes.
PMID- 28707053
TI - Impact of Sustained Virological Response to Interferon Therapy on Recurrence of
Hepatitis C Virus-Related Hepatocellular Carcinoma.
AB - BACKGROUND: Although achieving a sustained virological response (SVR) in
hepatitis C virus (HCV) infection is recognized as improving liver function and
reducing hepatocellular carcinoma (HCC) development, its impact on HCC recurrence
is unclear. This study investigated how preoperative SVR achievement by
interferon treatment affects HCC recurrence in patients undergoing hepatic
resection. METHODS: The study subjects were 521 patients with HCV infection who
underwent initial and curative hepatic resection for HCC. To adjust for
confounding factors between the SVR and non-SVR groups, propensity score-matching
analysis was performed. RESULTS: After propensity score matching, 45 of the 49
patients in the SVR group, and an equal number of the 472 patients in the non-SVR
group, were matched. The two groups had similar distributions of
clinicopathological characteristics. In the matched cohort, the 3-, 5-, and 7
year recurrence-free survival rates after surgery were 56, 45, and 37%,
respectively, in the SVR group, and 34, 23, and 7.2%, respectively, in the non
SVR group (p = 0.033). Additionally, the 3-, 5-, and 7-year overall survival
rates after surgery were 82, 80, and 75%, respectively, in the SVR group, and 78,
64, and 44%, respectively, in the non-SVR group (p = 0.065). The 1- and 2-year
cumulative recurrence rates in the early phase showed no significant difference
between the SVR and non-SVR groups (p = 0.27). however, the 3-, 5-, and 7-year
cumulative recurrence rates in the late phase were 14, 32, and 43%, respectively,
in the SVR group, and 33, 55, and 86%, respectively, in the non-SVR group (p =
0.037). CONCLUSION: Achievement of SVR may reduce postoperative recurrence after
hepatic resection.
PMID- 28707054
TI - Frequency and Management of Sleep Disturbance in Adults with Atopic Dermatitis: A
Systematic Review.
AB - INTRODUCTION: Intense nocturnal pruritus as well as the complex pathophysiology
of atopic dermatitis (AD) can severely affect sleep and become a major factor in
negatively impacting quality of life in adults. However, much of the literature
on sleep disturbance in AD patients is on the pediatric population, and it is not
well studied in adults. Furthermore, limited studies are available to guide
effective management of sleep disturbance in AD in general. We review the
literature to present the studies that have investigated the relationship between
AD and its effect on sleep in adults and provide an approach for clinicians
caring for this population. METHODS: A systematic literature search was conducted
through the PubMed and EMBASE databases using the search terms "atopic
dermatitis" OR "eczema" AND "sleep." The articles generated by the search and
their references were reviewed. RESULTS: A high prevalence of sleep disturbance
is experienced by adults with AD. The likelihood of sleep disturbance is much
higher in patients with AD compared to those without AD. Sleep disturbance
appears to worsen with AD severity. Pruritus and scratching appear to be large
contributors to sleep disturbance in adult patients with AD. CONCLUSION: It is
important that clinicians evaluate the severity of AD and ask general questions
about itching, sleep, impact on daily activities, and persistence of disease
during each patient visit and follow-up with the complaint of sleep disturbance.
Management of sleep disturbance in AD should focus on adequate disease control of
AD as well as possible medical interventions to help improve sleep. The
pathophysiology of sleep disturbance in AD is extremely complex, and further
research is needed to better understand the interplay of the immune system,
circadian rhythm, and environmental factors implicated in both AD and sleep.
PMID- 28707055
TI - Histological heterogeneity in primary and metastatic classic combined
hepatocellular-cholangiocarcinoma: a case series.
AB - Combined hepatocellular-cholangiocarcinoma (cHCC-CC) is a rare and aggressive
primary liver cancer with both hepatocellular and cholangiocellular
differentiation. Due to its bi-phenotypic component, cHCC-CC is a heterogeneous
tumour and histopathological analysis of metastatic deposits is poorly
characterized. In this retrospective study, we describe four patients in whom the
histology from resected specimens of both primary and recurrent and/or metastatic
tumour was available for comparison and immunohistochemical characterization. Our
study shows that recurrent or metastatic deposits replicate the heterogeneity of
the primary cHCC-CC, that even originally small foci of divergent differentiation
can become predominant later on and that hepatocellular and cholangiocellular
components can show different tropism in distant organs. In our experience, the
behaviour of recurrent/metastatic cHCC-CC is unpredictable and histological
examination is necessary to guide treatment options at present.
PMID- 28707056
TI - Comparison of Oncotype DX(r) Recurrence Score(r) with other risk assessment tools
including the Nottingham Prognostic Index in the identification of patients with
low-risk invasive breast cancer.
AB - Oncotype DX(r) is a gene expression assay that quantifies the risk of distant
recurrence in patients with hormone receptor positive early breast cancer,
publicly funded in Ireland since 2011. The aim of this study was to correlate
Oncotype DX(r) risk groupings with traditional histopathological parameters and
the results of other risk assessment tools including Recurrence Score-Pathology
Clinical (RSPC), Adjuvant Risk Index (Adj RI), Nottingham Prognostic Index (NPI)
and the Adjuvant! Online 10-year score (AO). Patients were retrospectively
identified from the histopathology databases of two Irish hospitals and patient
and tumour characteristics collated. Associations between categorical variables
were evaluated with Pearson's chi-square test. Correlations were calculated using
Spearman's correlation coefficient and concordance using Lin's concordance
correlation coefficient. Statistical analysis was performed using SPSS software,
version 22.0.In our 300 patient cohort, Oncotype DX(r) classified 59.7% (n = 179)
as low, 30% (n = 90) as intermediate, and 10.3% (n = 31) as high risk. Overall
concordance between the RS and RSPC, Adj RI, NPI, and AO was 67.3% (n = 202),
56.3% (n = 169), 59% (n = 177), and 36.3% (n = 109), respectively. All risk
assessment tools classified the majority of patients as low risk apart from the
AO 10-year score, with RSPC classifying the highest number of patients as low
risk. This study demonstrates that there is good correlation between the RS and
scores obtained using alternative risk tools. Concordance with NPI is strong,
particularly in the low-risk group. NPI, calculated from traditional
clinicopathological characteristics, is a reliable alternative to Oncotype DX(r)
in the identification of low-risk patients who may avoid adjuvant chemotherapy.
PMID- 28707057
TI - Application of testosterone supplementation in semen to improve sperm motility in
asthenozoospermic males.
AB - PURPOSE: To evaluate the effect of different concentrations and durations of
seminal testosterone supplementation upon the motility of sperm from
asthenozoospermic males. METHODS: Semen was collected from 41 infertile men with
asthenozoospermia. After liquefaction, 200 MUL was extracted from each semen
sample and divided equally into five groups for a negative control, a vehicle
control, and three experimental portions mixed with 4.75, 7.75, and 17.75 nmol/L
of testosterone, respectively. The sperm motility was evaluated at 5, 15, 30, and
45 min following the addition of testosterone. The supernatant from remaining
samples were sent for testosterone assay. Sperm viability was also evaluated
after 45 min. RESULTS: There was no difference in the number of samples in each
group which showed a 20% improvement in sperm motility. Group 3 showed a
significant retardation in the reduction of motility compared with Group 5 (P <
0.05). Semen samples with a final testosterone concentration of 4.51-10 nmol/L
showed a significant improvement in sperm motility when measured 5 min after
addition. In contrast, samples showing a rise in testosterone level above 10
nmol/L were associated with a reduction in both sperm motility and viability.
CONCLUSION: Despite sperm motility decreasing over time, supplementation of semen
samples with 4.75 nmol/L of testosterone could delay such reduction. A final
seminal testosterone concentration of 4.51-10 nmol/L appears to be optimal for
the best sperm motility.
PMID- 28707058
TI - Is there any relationship between adipocytokines and angiogenesis factors to
address endothelial dysfunction and platelet aggregation in untreated patients
with preeclampsia?
AB - PURPOSE: Preeclampsia is a multisystem disorder and its etiology remains still
unclear. Recent hypotheses rely on imbalance between angiogenic and
antiangiogenic factors and disruption of endothelial function of spiral arteries.
In addition; increased VTE (venous thromboembolism) risk is still unclear in
preeclampsia. Our aim was to investigate the relationship between endothelial
dysfunction, adipocytokines, platelet function, and vasculogenesis in
preeclampsia. METHODS: Plasma angiogenic (PlGF, VEGF), antiangiogenic factors
(sflt-1, endoglin) with adipocytokines (leptin, adiponectin, ghrelin),
endothelial dysfunction markers (vWF, NO), and platelet function markers (ADP and
collagen induced platelet aggregation, P-selectin) were examined in 30 early
onset, 22 late-onset preeclampsia, and 27 healthy pregnants. Enzyme-linked
immunosorbent assay (ELISA) was used to determine the serum biomarker levels
except NO. NO levels were determined using colorimetric method. RESULTS:
Endoglin, leptin, and vWF levels were increased in preeclampsia (P < 0.001),
whereas PlGF, P-selectin (P < 0.001), and col-induced platelet aggregation slope
(P < 0.05) were decreased in the same counterpart as compared to healthy
pregnants. Endoglin also correlated with sflt-1 in preeclamptic patients.
CONCLUSION: Increase in the levels of antiangiogenic factors and leptin herewith
decline in the level of other angiogenic factor PlGF, did not affect nitric oxide
and platelet aggregation markers significantly. Increased levels of vWF and
endoglin might be result of endothelial dysfunction, so our findings suggest that
an impaired angiogenesis may address endothelial dysfunction, but not platelet
aggregation for preeclampsia.
PMID- 28707059
TI - A prospective cohort study on the prediction of fetal distress and neonatal
status with arterial and venous Doppler measurements in appropriately grown term
fetuses.
AB - PURPOSE: To assess the predictive power of the cerebro-placental ratio (CPR) and
the venous-arterial index (VAI) for the development of intrapartum fetal distress
(FD) and neonatal intensive care unit (NICU) admission. METHODS: Fetal umbilical
artery, middle cerebral artery and umbilical vein Doppler measurements were
obtained before the active phase of labor in 311 singleton pregnancies at >=37
weeks. A continuous electronic fetal monitorization was applied, and an umbilical
cord blood sample was obtained for each participant. FD and NICU admission were
the primary outcomes. RESULTS: Labor was concluded as uncomplicated spontaneous
vaginal delivery (SVD) in 261 (83.9%) cases. The 22 (7.1%) FD cases were
subdivided into FD with NICU admission (n: 7; 2.3%) and without NICU admission
(n: 15; 4.8%). Six out of 7 (85.8%) FD with NICU admission cases were from
nulliparous pregnancies. The combinatory indices (VAI and CPR) reached the
highest sensitivity (31.8%) and negative predictive value (94.7%). None of the
fetuses, distressed or non-distressed, with CPR <= 10th percentile was born with
a cord pH < 7.20. CONCLUSION: FD frequency was increased in fetuses with a low
CPR or low VAI. However, the Doppler patterns were heterogeneous in both
subgroups: FD with and without NICU admission. FD seems to be a common endpoint
of different circulatory-metabolic disturbances. Parity affects the FD frequency
in a manner related but not limited to fetal arterial and venous circulation. Low
CPR could be a part of the adaptive mechanisms providing metabolic preparedness
for hypoxic episodes.
PMID- 28707060
TI - The psychological significance of play with imaginary companions in early
childhood.
AB - Although social play is common to many species, humans are unique in their
ability to extract some of the benefits of social play through imagination. For
example, in play with imaginary companions (ICs), children often practice skills
that might be useful for later adaptive social, relational, and emotional
functioning. While play with ICs does not provide the same immediate feedback
that play with real others affords, this imagined, quasisocial context allows
children to experiment with or rehearse events that might occur in real
relationships. This symbolic enactment of social relationships might afford
opportunities to experience not just social situations but all manner of positive
and negative emotions in a risk-free way. In addition, children's interactions
with real others around their ICs allow for negotiation of social roles in real
relationships. ICs also provide a forum for psychological distance that might
help young children manage their real relationships and engage in processes such
as negotiation and cooperation, which are needed for successful social
adaptation. Although play with ICs is clearly not of adaptive value in an
evolutionary sense, for the children who create them, ICs might hold
psychological significance for adaptive social development.
PMID- 28707061
TI - The evolutionary significance of pretend play: Two-year-olds' interpretation of
behavioral cues.
AB - Pretend play begins very early in human life. A key question is why, when
figuring out reality is young children's major developmental task, they engage in
its deliberate falsification. A second key question is how children know that
pretend events are not real. Here we report three experiments addressing the
latter question and providing indirect evidence for speculation on the first
question. Children (N = 96) were shown actors eating or pretending to eat from
covered bowls, and they had to indicate, on the basis of the actors' behavioral
signs, which actor was pretending to eat or had the real food. Even 24-month-olds
could do so when the contents of the bowls were shown before the actions, and
even when substitute objects were shown. However, when one of the bowls contained
imaginary objects (i.e., was empty), even 30-month-olds could not indicate which
actor was pretending. These studies show how the ability to interpret pretending
from behavioral cues develops gradually as children's representational abilities
become more free of contextual support. We propose that, from an evolutionary and
ontogenetic standpoint, pretend play might serve to heighten children's
sensitivity to social signs. This sensitivity could assist the development of
theory of mind, with which social pretend play is associated. In this way,
pretend play in humans might serve a similar purpose to play fighting in other
species: In both cases, play might sensitize the organism to social signs that
will allow for sophisticated coordination of social behavior later in life.
PMID- 28707062
TI - When an object appears unexpectedly: foot placement during obstacle circumvention
in children and adults with Developmental Coordination Disorder.
AB - Adjustments to locomotion to avoid an obstacle require a change to the usual
pattern of foot placement, i.e. changes to step length and/or step width.
Previous studies have demonstrated a difficulty in individuals with Developmental
Coordination Disorder (DCD) in controlling stability while both stepping over and
while circumventing an obstacle. In a previous study, we have considered the way
in which individuals with DCD prepare for the possibility of an obstacle
appearing (Wilmut and Barnett in Exp Brain Res 235:1531-1340, 2017). Using a
parallel data set from this same task on the same individuals, the aim of the
current study was to investigate the exact nature of changes in foot placement
during obstacle avoidance, as this was not clear from previous work. Children and
adults aged from 7 to 34 years of age took part in the study. Forty-four met the
criteria for a diagnosis of DCD and there were 44 typically developing (TD) age
and gender-matched controls. Participants walked at a comfortable pace down an 11
m walkway; on 6 out of 36 trials a 'gate' closed across their pathway which
required circumvention. These 6 'gate close' trials were analysed for this study.
The number and magnitude of step length and step width adjustments were similar
across the DCD and TD groups, however, the younger children (7-11 years) made a
greater number of early adjustments compared to the older children and adults (12
34 years of age). In contrast the adults made a greater number of adjustments
later in the movement compared to the children. In terms of foot placement
adjustments a clear preference was seen across all participants to use
adjustments which resulted in reducing step length, stepping away from the
obstacle and a combination of these. Apart from subtle differences, the
individuals with DCD make step placements to circumvent an obstacle in line with
their peers. It is suggested that the choice of foot placement strategy in
individuals with DCD, although in line with their peers, may not be optimal for
their level of motor ability.
PMID- 28707063
TI - Liquid chromatography-mass spectrometry methods for the intracellular
determination of drugs and their metabolites: a focus on antiviral drugs.
AB - Understanding the efficacy and/or toxicity of most drugs requires effective
intracellular measurements of the drug and its metabolites. Nevertheless, the
most common plasma marker of the biological effect of the drug is the area under
the curve. Compared with drug determination in whole blood or urine, various
difficulties occur in the development of analytical methods for intracellular
measurements. We propose step-by-step guidelines to develop an analytical method
exploring intracellular concentrations of antivirals and/or their metabolites.
These guidelines are illustrated with the most sensitive liquid chromatography
mass spectrometry methods developed for human in vivo and in vitro studies. We
summarize 18 studies that provided methods to explore intracellular
concentrations of antivirals since 2002. To explore intracellular metabolites,
two different approaches can be envisaged. The direct approach, most frequently
using ion-pairing agents, is fast and requires only a small sample but is
expensive. The indirect approach is the more widely used approach, but is
cumbersome and time-consuming. In both cases, liquid chromatography-mass
spectrometry has become the method of choice to determine intracellular drug
concentrations with high sensitivity. These methods may increase our
understanding of drug behavior in organisms. This is true for preclinical studies
where the mechanism of action, the metabolism, and the toxicity of drugs are
explored. It is also true for clinical applications when dose adjustment is
needed and cannot rely on blood concentrations. Graphical Abstract Direct and
indirect approaches to measure intracellular concentrations.
PMID- 28707064
TI - Development of a lateral flow dipstick immunoassay for evaluation of folate
levels in maize.
AB - Folates (vitamin B9) are essential for all organisms as cofactors for one-carbon
metabolism. However, measurement of folates is technically complicated and time
consuming. In this study, we developed a dipstick immunoassay using a folate
specific monoclonal antibody (mAb), allowing rapid and low-cost detection of
folates. The indicator range of the dipstick for 5-formylterahydrofolate (5-CHO
THF), 5-methyltetrahydrofolate (5-CH3-THF) and their polyglutamyl forms was 100
200 ng mL-1; moreover, no cross-reactivity was observed with tetrahydrofolate
(THF) or 5,10-methenyltetrahydrofolate (5,10-CH=THF) at 500 ng mL-1, or with the
folate precursors pterin-6-COOH, p-aminobenzoate (pABA), and L-glutamate, or with
the folate analogues methotrexate and 10-formyltetrahydrofolate (10-CHO-THF) at
up to 1000 ng mL-1. The dipstick immunoassay was tested in maize seeds; the
results classified the seeds into those with low, moderate, and high levels of
folates, and were in agreement with those of liquid chromatography-mass
spectrometry. Thus, we conclude that the dipstick assay will provide a versatile
tool to facilitate large-scale screening of maize rich in folates. Graphical
Abstract The dipstick based immunoassay for analyzing folate level in maize.
PMID- 28707065
TI - Nasopharyngeal pertussis toxin IgA antibodies in the diagnosis of pertussis in
Australian community patients.
AB - Nasopharyngeal aspirate (NPA) Bordetella pertussis-specific IgA antibody assay
using whole-cell (WC) antigen has previously been shown to have promise in the
diagnosis of patients with suspected pertussis. Recently, the use of WC assays in
serum have been replaced by pertussis toxin (PT) because of specificity concerns.
In this study, PT and WC B. pertussis-specific IgA antibody was assayed in 491
NPAs. Specimens also had molecular testing for the presence of B. pertussis and
B. parapertussis as per the usual laboratory protocol. Positive concordance of
the two serological assays was 51.2%, negative concordance was 67.5% and total
concordance was 75.8%. 99 of 119 discordant specimens were resolved by utilising
the B. pertussis polymerase chain reaction (PCR) result and clinical status, and
yielded a sensitivity of 57.6% and a specificity 97.7% for WC, with 90.2% and
93.1%, respectively, for the PT assay (p < 0.00025 and 0.025-0.01). In contrast,
the sensitivity of PCR was only 19.1% in this cohort. We conclude that
specificity is not a significant issue for mucosal pertussis-specific IgA assays
using WC, but the superior sensitivity of the PT assay favours the latter method.
This assay, combined with PCR assays, should significantly improve the diagnosis
of pertussis cases.
PMID- 28707067
TI - Phagocytosis of Escherichia coli biofilm cells with different aspect ratios: a
role of substratum material stiffness.
AB - Bacterial biofilms play an important role in chronic infections due to high-level
tolerance to antibiotics. Thus, it is important to eradicate bacterial cells that
are attached to implanted medical devices of different materials. Phagocytosis is
a key process of the innate immunity to eliminate invading pathogens. Previous
research demonstrated that the efficiency of phagocytosis is affected by the
aspect ratio of polymer beads. Recently, we reported that the stiffness of
polydimethylsiloxane (PDMS) influences Escherichia coli biofilm formation and the
biofilm cells on stiff (5:1) PDMS are 46.2% shorter than those on soft (40:1)
PDMS. Based on these findings, we hypothesized that E. coli cells attached on
stiff PDMS can be more effectively removed via phagocytosis. This hypothesis was
tested in the present study using viability assays, flow cytometry, and cell
tracking. The results revealed that shorter E. coli cells detached from stiff
PDMS were easier to be phagocytized than the longer cells from soft PDMS
surfaces. Furthermore, macrophage cells were found to be more motile on stiff
PDMS surfaces and more effective at phagocytosis of E. coli cells attached on
these surfaces. These results may help the design of better biomaterials to
reduce fouling and associated infections.
PMID- 28707068
TI - Analysis of stable 1,2-dichlorobenzene-degrading enrichments and two newly
isolated degrading strains, Acidovorax sp. sk40 and Ralstonia sp. sk41.
AB - Stable degrading 1,2-dichlorobenzene (1,2-DCB) enrichments were generated from
original contaminated soil and groundwater via enrichment procedures using a
mineral salt medium containing 1,2-DCB as the sole carbon and energy source. Four
transferred enrichments showed stable 1,2-DCB-degrading ability and completely
degraded 1,2-DCB within 32 h. PCR-denaturing gradient gel electrophoresis (DGGE)
and 16S rRNA gene clone library analyses indicated that two bacterial strains,
belonging to Acidovorax spp. and Ralstonia spp., respectively, were the
predominant organisms in each enrichment. Moreover, these strains maintained a
stable coexistence in the four transferred enrichments. These two bacteria were
subsequently identified as Acidovorax sp. strain sk40 and Ralstonia sp. strain
sk41. Strain sk40 was more tolerant to higher concentrations of 1,2-DCB than
strain sk41, while strain sk41 maintained a shorter degradation time under lower
concentrations of 1,2-DCB. Notably, however, both strains exhibited similar
growth rates and degradation rates in media containing 40 mg/l 1,2-DCB, as well
as complete degradation of the 1,2-DCB (40 mg/l) within 32 h. It is expected that
these two strains will be used in future applications of bioremediation of 1,2
DCB contamination.
PMID- 28707069
TI - Variants in the PRPF8 Gene are Associated with Glaucoma.
AB - Glaucoma is the cause of irreversible blindness worldwide. Mutations in six genes
have been associated with juvenile- and adult-onset familial primary open angle
glaucoma (POAG) prior to this report but they explain only a small proportion of
the genetic load. The aim of the study is to identify the novel genetic cause of
the POAG in the families with adult-onset glaucoma. Whole exome sequencing (WES)
was performed on DNA of two affected individuals, and predicted pathogenic
variants were evaluated for segregation in four affected and three unaffected
Dutch family members by Sanger sequencing. We identified a pathogenic variant
(p.Val956Gly) in the PRPF8 gene, which segregates with the disease in Dutch
family. Targeted Sanger sequencing of PRPF8 in a panel of 40 POAG families (18
Pakistani and 22 Dutch) revealed two additional nonsynonymous variants
(p.Pro13Leu and p.Met25Thr), which segregate with the disease in two other
Pakistani families. Both variants were then analyzed in a case-control cohort
consisting of Pakistani 320 POAG cases and 250 matched controls. The p.Pro13Leu
and p.Met25Thr variants were identified in 14 and 20 cases, respectively, while
they were not detected in controls (p values 0.0004 and 0.0001, respectively).
Previously, PRPF8 mutations have been associated with autosomal dominant
retinitis pigmentosa (RP). The PRPF8 variants associated with POAG are located at
the N-terminus, while all RP-associated mutations cluster at the C-terminus,
dictating a clear genotype-phenotype correlation.
PMID- 28707070
TI - Functional Role of Matrix gla Protein in Glioma Cell Migration.
AB - Glioblastoma multiforme (GBM) is the most common and aggressive brain tumor
subtype. Despite that metastasis of GBM beyond the central nervous system (CNS)
is rare, its malignancy is attributed to the highly infiltration trait, leading
to the difficulty of complete surgical excision. Matrix gla protein (MGP) is a
vitamin K-dependent small secretory protein, and functions as a calcification
inhibitor. The involvement of MGP function in glioma cell dynamics remains to be
clarified. The study showed that a low proliferative rat C6 glioma cell line
named as C6-2 exhibited faster migratory and invasive capability compared to that
observed in a high tumorigenic rat C6 glioma cell line (called as C6-1).
Interestingly, C6-2 cells expressed higher levels of MGP molecules than C6-1
cells did. Lentivirus-mediated short hairpin RNA (shRNA) against MGP gene
expression (MGP-KD) in C6-2 cells or lentivirus-mediated overexpression of MGP
transcripts in C6-1 cells resulted in the morphological alteration of the two
cell lines. Moreover, MGP-KD caused a decline in cell migration and invasion
ability of C6-2 cells. In contrast, increased expression of MGP in C6-1 cells
promoted their cell migration and invasion. The observations were further
verified by the results from the implantation of C6-1 and C6-2 cells into ex vivo
brain slice and in vivo rat brain. Thus, our results demonstrate that the
manipulation of MGP expression in C6 glioma cells can mediate glioma cell
migratory activity. Moreover, our findings indicate the possibility that high
proliferative glioma cells expressing a high level of MGP may exist and
contribute to tumor infiltration and recurrence.
PMID- 28707071
TI - Retraction Note to: miR-124 Acts as a Tumor Suppressor in Glioblastoma via the
Inhibition of Signal Transducer and Activator of Transcription 3.
PMID- 28707072
TI - Catechol-O-Methyltransferase Val158Met Polymorphism on Striatum Structural
Covariance Networks in Alzheimer's Disease.
AB - The catechol-O-methyltransferase enzyme metabolizes dopamine in the prefrontal
axis, and its genetic polymorphism (rs4680; Val158Met) is a known determinant of
dopamine signaling. In this study, we investigated the possible structural
covariance networks that may be modulated by this functional polymorphism in
patients with Alzheimer's disease. Structural covariance networks were
constructed by 3D T1 magnetic resonance imaging. The patients were divided into
two groups: Met-carriers (n = 91) and Val-homozygotes (n = 101). Seed-based
analysis was performed focusing on triple-network models and six striatal
networks. Neurobehavioral scores served as the major outcome factors. The role of
seed or peak cluster volumes, or a covariance strength showing Met-carriers > Val
homozygotes were tested for the effect on dopamine. Clinically, the Met-carriers
had higher mental manipulation and hallucination scores than the Val-homozygotes.
The volume-score correlations suggested the significance of the putaminal seed in
the Met-carriers and caudate seed in the Val-homozygotes. Only the dorsal-rostral
and dorsal-caudal putamen interconnected peak clusters showed covariance strength
interactions (Met-carriers > Val-homozygotes), and the peak clusters also
correlated with the neurobehavioral scores. Although the triple-network model is
important for a diagnosis of Alzheimer's disease, our results validated the role
of the dorsal-putaminal-anchored network by the catechol-O-methyltransferase
Val158Met polymorphism in predicting the severity of cognitive and behavior in
subjects with Alzheimer's disease.
PMID- 28707073
TI - Protective Effects of Spatholobi Caulis Extract on Neuronal Damage and Focal
Ischemic Stroke/Reperfusion Injury.
AB - Neuronal apoptotic cell death plays an important role in many neurological
disorders, including Alzheimer's disease, Parkinson's disease, and ischemic
stroke. Spatholobi Caulis (SC) has been widely used in traditional herbal
medicine for the treatment of cancer, inflammation, viral infection, and anemia.
However, the protective effects of SC extract (SCE) against apoptotic cell death
in the brain have not been reported. We investigated the protective effects of
SCE against neuronal injury etoposide-induced neurotoxicity and in rats subjected
to focal transient ischemic stroke middle cerebral artery occlusion (MCAO) for 45
min, followed by 7 days of reperfusion. The in vitro study demonstrated that SCE
protected cells against etoposide-induced cell viability loss in SH-SY5Y cells.
Apoptotic phenotypes, such as cleaved PARP and caspase-3, and oxidative stress in
etoposide-treated cells were ameliorated by SCE treatment. In MCAO-reperfusion
injury, SCE promoted neuronal survival and level of brain-derived neurotrophic
factor (BDNF) by reducing glial activation, oxidative stress, and apoptosis in
the ipsilateral cortex. These results indicated that SCE exerted protective
effects under etoposide treatment and in a MCAO-reperfusion model by reducing JNK
and p38 MAPK activation. This study presents the first evidence that SCE has
therapeutic potential for the treatment of ischemic stroke or neurological
disorder-related cell death.
PMID- 28707074
TI - Presenilin-1 Delta E9 Mutant Induces STIM1-Driven Store-Operated Calcium Channel
Hyperactivation in Hippocampal Neurons.
AB - Presenilins regulate calcium homeostasis in the endoplasmic reticulum, and
dysregulation of intracellular calcium has been implicated in the pathogenesis of
Alzheimer disease. Elevated presenilin-1 (PS1) holoprotein levels have been
detected in postmortem brains of patients carrying familial Alzheimer disease
(FAD) PS1 mutations. This study examines the effect of the FAD presenilin mutant
that lacks the ninth exon (PS1 ?E9) and does not undergo endoproteolysis on store
operated calcium (SOC) entry. Significant enhancement of SOC channel activation
was detected by electrophysiological measurements in hippocampal neurons with PS1
?E9 mutant expression. Here, we show that (i) the hyperactivation of SOC channels
is mediated by the STIM1 sensor and can be attenuated by STIM1 knockdown or 2
aminoethoxydiphenyl borate application, (ii) the STIM2 is not involved in
pathological changes of SOC entry, (iii) the pathological SOC entry demonstrates
properties of both TRPC and Orai subunit composition, and (iiii) transgenic
Drosophila flies with PS1 ?E9 expression in the cholinergic neuron system show
short-term memory loss, which can be abolished by 2-aminoethoxydiphenyl borate
feeding.
PMID- 28707075
TI - LINE-1 Hypermethylation in Serum Cell-Free DNA of Relapsing Remitting Multiple
Sclerosis Patients.
AB - Concentrations of cell-free DNA (cfDNA) circulating in blood and its epigenetic
variation, such as DNA methylation, may provide useful diagnostic or prognostic
information. Long interspersed nuclear element-1 (LINE-1) constitutes
approximately 20% of the human genome and its 5'UTR region is CpG rich. Due to
its wide distribution, the methylation level of the 5'UTR of LINE-1 can serve as
a surrogate marker of global genomic DNA methylation. The aim of the current
study was to investigate whether the methylation status of LINE-1 elements in
serum cell-free DNA differs between relapsing remitting multiple sclerosis (RRMS)
patients and healthy control subjects (CTR). Serum DNA samples of 6 patients and
6 controls were subjected to bisulfite sequencing. The results showed that the
methylation level varies among distinct CpG sites in the 5'UTR of LINE-1 repeats
and revealed differences in the methylation state of specific sites in this
element between patients and controls. The latter differences were largely due to
CpG sites in the L1PA2 subfamily, which were more frequently methylated in the
RRMS patients than in the CTR group, whereas such differences were not observed
in the L1HS subfamily. These data were verified by quantitative PCR using
material from 18 patients and 18 control subjects. The results confirmed that the
methylation level of a subset of the CpG sites within the LINE-1 promoter is
elevated in DNA from RRMS patients in comparison with CTR. The present data
suggest that the methylation status of CpG sites of LINE repeats could be a basis
for development of diagnostic or prognostic tests.
PMID- 28707076
TI - Correlation of Changes in Patient-Reported Quality of Life With Physician-Rated
Global Impression of Change in Patients With Narcolepsy Participating in a
Clinical Trial of Sodium Oxybate: A Post Hoc Analysis.
AB - INTRODUCTION: Narcolepsy patients report lower health-related quality of life
(HRQoL) than the general population, as measured by the Short Form-36 Health
Survey (SF-36). This analysis evaluated whether changes in SF-36 correlated with
physician-rated Clinical Global Impression of Change (CGI-C). METHODS: Data were
from 209 of 228 narcolepsy patients participating in an 8-week clinical trial of
sodium oxybate. Changes from baseline for SF-36 subscales (Physical Functioning,
Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role
Emotional, and Mental Health) and the summary scores were evaluated for
correlation with CGI-C overall and by treatment group. Correlations were
calculated using the Pearson product-moment correlation coefficient (r). RESULTS:
Correlations described an inverse relationship in scores, but a direct
relationship in improvement; lower CGI-C scores (i.e., better) were associated
with higher SF-36 subscale scores (i.e., improved HRQoL). Moderate and
significant correlations were observed for Vitality (r = -0.464; P < 0.0001) and
Role Physical (r = -0.310; P < 0.0001) subscales, but weak correlations were
observed with other subscales including summary scores. Correlations were
stronger at higher sodium oxybate doses for most SF-36 subscales. CONCLUSION:
Some aspects of HRQoL, measured by the SF-36, may be associated with narcolepsy.
In particular, Vitality (indicative of energy and tiredness) and Role Physical
(impact of physical function on daily roles) moderately correlated with overall
change in status observed by clinicians. However, lack of strong correlations
between SF-36 and CGI-C indicates differences in patient and clinician
perspectives of disease, and suggest a need for broader assessment of the impact
of narcolepsy and its treatment on patients. FUNDING: Jazz Pharmaceuticals.
PMID- 28707077
TI - Association of ABCB1 promoter methylation with aspirin exposure, platelet
function, and clinical outcomes in Chinese intracranial artery stenosis patients.
AB - PURPOSE: DNA methylation typically acts to repress gene transcription. ABCB1 is
involved in the intestinal absorption of aspirin. We aimed to investigate the
impact of methylation status of ABCB1 promoter on aspirin exposure, platelet
function, and clinical outcomes in Chinese intracranial artery stenosis patients
receiving antiplatelet treatment. METHODS: Symptomatic intracranial artery
stenosis patients (without carrying CYP2C19 loss-of-function alleles) receiving
antiplatelet therapy were enrolled in this study. The clinical outcome was the
composite events, vascular death, recurrent ischemic stroke, myocardial
infarction, or transit ischemic attack. Patients were divided into cases and
controls based on the 1-year follow-up. Venous blood samples were collected for
methylation level analysis, drug determination, and thromboelastographic assay.
The Pearson correlation analysis was used to investigate the association of
potential influencing factors and visualize them using three-dimensional plot.
Receiver operator curves were applied to compare the diagnostic performance of
potential factors and calculate the cut-off values. RESULTS: We assessed 438
patients, 30 (non-carrier of CYP2C19 loss-of-function alleles) experienced
adverse clinical events, and 30 patients without clinical events were selected as
controls. Total of 34 CpG methylation sites were investigated for ABCB1
methylation. Compared with controls, the cases had significant lower methylation
levels (CpG21.22), lower salicylic acid concentration, and lower arachidonic acid
inhibition (P value < 0.05). A cut-off point of CpG21.22 0.015 was identified
with a specificity of 0.759. CONCLUSION: ABCB1 hypomethylation is associated with
lower drug absorption, higher platelet reactivity, and an increased risk of
ischemic events in our patients. This may provide important insights into the
research of aspirin resistance.
PMID- 28707078
TI - CTLA-4 expression in the non-small cell lung cancer patient tumor
microenvironment: diverging prognostic impact in primary tumors and lymph node
metastases.
AB - The immune checkpoint receptor CTLA-4 plays a crucial part in negatively
regulating T cell activation and maintaining self-tolerance. It is frequently
overexpressed in a variety of malignancies, yet its prognostic impact in non
small cell lung cancer (NSCLC) remains unclear. We constructed tissue microarrays
from tumor tissue samples and evaluated the immunohistochemical expression of
CTLA-4 in 536 patients with primary resected stage I-IIIA NSCLC. Expression of
CTLA-4 was analyzed in tumor and stromal primary tumor tissue and in locoregional
metastatic lymph nodes. CTLA-4 expression in neither tumor epithelial cells (T
CTLA-4) nor stromal cells (S-CTLA-4) of primary tumors was significantly
associated with disease-specific survival (DSS) in all patients. However, high S
CTLA-4 expression independently predicted significantly improved DSS in the
squamous cell carcinoma subgroup (HR 0.62, 95% CI 0.41-0.93, P = 0.021). In
contrast, there was an independent negative prognostic impact of T-CTLA-4
expression in metastatic lymph nodes (HR 1.65, 95% CI 1.03-2.65, P = 0.039). Our
results indicate that the expression of CTLA-4 has diverging prognostic impacts
in metastatic NSCLC lymph nodes versus primary tumors. The presented results
highlight important differences in the tumor microenvironments of primary and
metastatic NSCLC tissues, and have potential to guide treatment and clinical
sampling strategies.
PMID- 28707079
TI - Down-regulation of miR-23a inhibits high glucose-induced EMT and renal
fibrogenesis by up-regulation of SnoN.
AB - It has been reported that transforming growth factor-beta1 (TGF-beta1) signaling
plays an important role in the development of diabetic nephropathy (DN). The
nuclear transcription co-repressor Ski-related novel protein N (SnoN) is a
critical negative regulator of TGF-beta1/Smad signal pathway, involving in tubule
epithelial-mesenchymal transition (EMT), extracellular matrix (ECM) accumulation,
and tubulointerstitial fibrosis. In this study, we focused on miR-23a as a
regulator of SnoN. Our purpose is to study the effects of miR-23a on high glucose
(HG)-induced EMT process and ECM deposition in HK2 cells. We found that miR-23a
was up-regulated in renal tissues of diabetic patients and HG-induced HK2 cells.
Besides, the high level of miR-23a was closely associated with decreased SnoN
expression. Knockdown of miR-23a increased SnoN expression and in turn suppressed
HG-induced EMT and renal fibrogenesis. Introduction of miR-23a decreased SnoN
expression and enhanced the profibrogenic effects of HG on HK2 cells. Next,
bioinformatics analysis predicted that the SnoN was a potential target gene of
miR-23a. Luciferase reporter assay demonstrated that miR-23a could directly
target SnoN. We demonstrated that overexpression of SnoN was sufficient to
inhibit HG-induced EMT and renal fibrogenesis in HK2 cells. Furthermore, down
regulation of SnoN partially reversed the protective effect of miR-23a knockdown
on HG-induced EMT and renal fibrogenesis in HK2 cells. Collectively, miR-23a and
SnoN significantly impact on the progression of HG-induced EMT and renal
fibrogenesis in vitro, and they may represent novel targets for the prevention
strategies of renal fibrosis in the context of DN.
PMID- 28707080
TI - Reproductive outcomes of anestrous goats supplemented with spineless Opuntia
megacantha Salm-Dyck protein-enriched cladodes and exposed to the male effect.
AB - The possible influence of the "male effect" upon reproductive outcomes of adult
anestrous goats under marginal rangeland conditions and supplemented with protein
enriched Opuntia megacantha Salm-Dyck was evaluated. Reproductive variables
included: estrus percentage (EST, %), estrus latency (ESL, hours), ovulation
percentage (OP, %), ovulation rate (OR, units), average largest follicle at
ovulation (LFO, mm), largest corpus luteum (LCL, mm), embryo number (EBN, units),
and embryo implantation percentage (EIP, %). During early May, anestrous mix
breed adult goats (Criollo x Alpine-Saanen-Nubian; n = 38, 26 degrees N) were
randomly distributed to (1) Control (CC; n = 12), (2), Non-enriched Opuntia (NEO;
n = 14), and (3) Protein-enriched Opuntia (PEO; n = 12). Neither LW (P > 0.05)
nor BCS (P > 0.05) or any of the evaluated ovarian variables differed (P > 0.05)
among treatments; EST = 89.66%, ESL = 53.66 h, OP = 70.33%, OR = 1.07 units, LFO
= 4.5 mm, LCL = 9.6 mm, EBN = 0.94 embryos, and EIP = 48.66%. Irrespective of
nutritional supplementation regime, all goats denoted an increased response to
the male effect just in the middle of the anestrous season and managed under
marginal grazing conditions during the dry season (May to June; 26 degrees N).
The use of the male effect successfully invoked neurophysiological pathways to re
activate ovarian follicular and luteal pathways during the natural anestrous
season in the female goat. Yet, such successful physiological scenario was not
equally exerted to promote an increased embryo implantation rate; this issue
claims further consideration. Therefore, it is essential to align not only the
peri-conceptional but also the peri-implantation stages to the best suited
environmental conditions in the rangeland, in order to increase both reproductive
and economic efficiency while promoting sustainability in those rangeland-based
marginal goat production systems.
PMID- 28707081
TI - Evaluation of clinical pathology parameters in fecal PCR-positive or PCR-negative
goats for Johne's disease.
AB - Johne's disease (JD) is an economically important infectious disease of ruminants
caused by Mycobacterium avium subsp. paratuberculosis (MAP). This study evaluated
the differences in various hematological and biochemical parameters between
healthy goats and goats with JD. Forty goats were chosen randomly from a herd
endemic for JD. A complete physical examination was performed. Blood and fresh
fecal samples were collected from each goat. A complete blood cell (CBC) count
and a protein electrophoresis were performed. Polymerase chain reaction (PCR) on
fecal samples was performed in order to divide goats into two groups: group A
"positive PCR on feces"; and group B "control (negative)." A Student's t test was
performed for each parameter to verify differences between groups A vs B. Twenty
goats were included in each group. Clinical signs likely related to JD were found
in the history of 4/40 (10%) goats, while 36/40 (90%) goats were reported to be
asymptomatic. CBC and electrophoresis values were within reference intervals in
both groups. No differences were found for CBC parameters between the two groups.
Values for alpha 1, beta, gamma globulins, and total protein (TP) were
statistically higher in group A vs those in group B, while those for albumin and
albumin/globulin (A/G) ratio were lower. An increase in TP, hypoalbuminemia, and
hypergammaglobulinemia has been reported in group A, while no abnormalities were
found concerning CBC. JD-positive goats seem to show earlier clinical
pathological alternations than clinical signs. Protein electrophoresis may help
the diagnosis of JD in asymptomatic goat herds, acting as an economical screening
method.
PMID- 28707082
TI - Next-gen cancer research.
PMID- 28707083
TI - Layered defense: how mucus and tight junctions seal the intestinal barrier.
AB - The colonic mucosa provides a vital defensive barrier separating the body from
the microbial populations residing in the intestinal lumen. Indeed, growing
evidence shows that loss of this barrier may cause disease or exacerbate disease
progression. The loss of barrier integrity increases the translocation of
bacterial antigens and stimulates inflammation in the intestinal mucosa, which is
the central pathological feature of inflammatory bowel diseases (IBDs). This
review focuses on how intestinal mucus and intercellular tight junctions (TJs)
act together to maintain the integrity of the colonic barrier and how barrier
integrity is dysregulated in IBD.
PMID- 28707084
TI - A novel plant DNA extraction method using filter paper-based 96-well spin plate.
AB - MAIN CONCLUSION: A simple, low cost and safe method using homemade filter paper
based 96-well spin plates and homemade solutions was developed for high
throughput plant DNA extraction to use in molecular marker analysis. A low cost
and safe method was developed for high throughput extraction of plant DNA for
molecular marker analysis. In this method, we describe a simple way to prepare 96
well spin plate using filter paper, a plant material product for DNA binding.
Such filter paper-based spin plate can combine with homemade non-toxic buffers
for high throughput extraction of plant DNA. We confirmed that filter paper is an
efficient solid-phase DNA binding material and comparable to silicon-based glass
fiber filters adopted in commercial DNA extraction kits, and that plant DNA
extracted by this method can be readily used as template for PCR. The efficacy of
this method was also fully demonstrated by molecular marker analysis in
segregating populations of tomato. Due to greatly reduced expense compared to
commercial kits, this method is of great value for small labs with limited
resources.
PMID- 28707085
TI - Is submucosal fat injection effective in atrophic rhinitis? An experimental
animal study.
AB - Atrophic rhinitis (AR) is a disease characterized by the extensive dilatation of
the nasal cavity and atrophy of the mucosa, submucosa and bone tissue. Its
etiological factors are unknown. There is not a satisfying treatment yet and the
treatment of the functional impairment in the atrophic cells is still subject to
investigation. The objective of this study is to determine at the
histopathological level the possible effects of the submucosal fat injection in
an experimental model of AR. 12 albino Wistar-Hannover male rats were included in
the study. AR was induced with the Pasteurella multocida toxin, which was diluted
with saline. As one of the rats died during the study, it was excluded from the
evaluation. The right nasal cavities of all rats (11 nasal cavities) were defined
as the control group (Group 1). Fat tissue obtained from the abdominal area was
injected in the seven left nasal cavities (Group 2). All injections, which were
done to the abdominal regions were also done in the left nasal cavities of the
remaining four rats, which constituted the sham group (Group 3). After 14 days,
all rats were decapitated and the squamous metaplasia and keratinization in the
superficial epithelium, degeneration, vacuolar changes in the basal layer,
congestion, inflammatory infiltration, vascular proliferation and glandular
atrophy in the submucosa are histopathologically classified. The results were
analyzed with statistical methods. Although glandular atrophy was significantly
regressed in the fat injection group (Group 2) compared to other groups (p <
0.05), the remaining parameters did not show any significant difference among
these three groups. The histopathological effect of the fat injection was modest.
We concluded that fat injection treatment has no or at the most a very limited
effect in the treatment of atrophic rhinitis.
PMID- 28707086
TI - Efficacy of hyaluronic acid and hydroxyethyl starch in preventing adhesion
following endoscopic sinus surgery.
AB - Adhesion is a major complication of endoscopic sinus surgery that may lead to
recurrence of chronic rhinosinusitis, necessitating revision surgery. The purpose
of this study was to evaluate the effect of hyaluronic acid and hydroxyethyl
starch (HA-HES) relative to hyaluronic acid and carboxymethylcellulose (HA-CMC)
with regard to anti-adhesion effect. In this multi-center, prospective, single
blind, randomized controlled study, 77 consecutive patients who underwent
bilateral endoscopic sinus surgery were enrolled between March 2014 and March
2015. HA-HES and HA-CMC were applied to randomly assigned ethmoidectomized
cavities after the removal of middle meatal packing. At the 1st, 2nd and 4th
weeks after surgery, the presence and grades of adhesion, edema, and infection
were, respectively, examined via endoscopy by a blinded assessor. The incidence
and grades of adhesion at the 2-week follow-up were significantly less in the HA
CMC group than in the HA-HES group (p < 0.05). However, with the exception of
week 2, there were no significant differences in the incidence or grades of
adhesion, edema, and infection between the two groups. When the primary endpoint
the presence of adhesion at the 4-week follow-up-was compared between two groups,
the incidence of adhesion in HA-HES group at the 4-week follow-up was 32% and in
HA-CMC was 41.3%, indicating that HA-HES was not inferior to HA-CMC in terms of
anti-adhesive effect. No severe adverse reactions were noted during the study
period. In conclusion, HA-HES is a safe substitutional anti-adhesion agent that
has equivalent effect as HA-CMC after endoscopic sinus surgery.
PMID- 28707087
TI - Jay Grosfeld, MD, FACS, FAAP, FRCS, FRCPS, FRSH (1935-2016).
PMID- 28707088
TI - Prognostic Significance of Lymphocyte Counts in Colon Cancer Patients Treated
with FOLFOX Chemotherapy.
AB - PURPOSE: There is increasing interest in immune function in combination with
chemotherapy for cancer treatment. However, the effects of chemotherapy on the
human immune system remain to be determined. The aim of this study was to
investigate the prognostic impact of lymphocyte and neutrophil counts in colon
cancer patients who were treated with curative surgery and adjuvant chemotherapy.
METHODS: Two hundred thirty-one patients with colon cancers who underwent
curative surgery and FOLFOX adjuvant chemotherapy between November 2005 and
December 2011 were included. Oncologic outcomes were analyzed with neutrophil
count, lymphocyte count, and neutrophil-to-lymphocyte ratio (NLR) before and
after chemotherapy. RESULTS: The 5-year DFS rate was lower in colon cancer
patients with low lymphocyte count during chemotherapy (61.9 vs. 76.7%, P =
0.026). Cox multivariate analysis demonstrated that low lymphocyte count during
chemotherapy was independently associated with poor disease-free survival (HR
1.829; 95% CI 1.096-3.050; P = 0.021) in colon cancer patients who underwent
FOLFOX adjuvant chemotherapy. CONCLUSION: Lymphocyte count during chemotherapy is
a strong predictor of worse disease-free survival in colon cancer patients who
have undergone FOLFOX adjuvant chemotherapy.
PMID- 28707089
TI - Fracture risk reduction with use of dipeptidyl peptidase-4 inhibitors: response
to Driessen et al.
PMID- 28707090
TI - Fracture risk reduction with use of dipeptidyl peptidase-4 inhibitors: is there
immortal time bias?
PMID- 28707091
TI - [Fluorescein, indocyanine green and optical coherence tomography angiography in
patients with native exudative age-related macular degeneration].
AB - INTRODUCTION: The newly developed optical coherence tomography angiography (OCT
A) has provided new means to depict the vascular plexus in neovascular age
related macular degeneration (nAMD). If these images are to be used as a basis
for therapeutic decisions, it is of vital importance to classify choroidal
neovascularization (CNV) as either classical or occult. This study aimed at
comparing the findings in OCT-A imaging of CNV with the traditional multimodal
imaging through fluorescein angiography (FLA) and indocyanine green angiography
(ICGA). METHODS: For this investigation 13 eyes from 13 patients with CNV on the
basis of untreated nAMD were studied using FLA, ICGA, spectral domain OCT and OCT
A. All CNV were classified on the basis of SD-OCT and OCT-A images by two
independent raters. Thereafter FLA and ICGA images were analyzed to set the gold
standard for the classification and the ratings were compared to the previous SD
OCT and OCT-A results. RESULTS: 88% of eyes were correctly classified as either
classical or occult CNV on the basis of SD-OCT and OCT-A images. Based on the CNV
subgroups, 93% of classical CNV were identified using OCT-A images. In contrast
occult CNV was correctly classified in 83% of patients. The interrater agreement
was 77%. In general it was noted that the more the retina was pathologically
altered, e. g. by edema or vascular pigment epithelium detachment, the harder it
became to correctly classify the CNV. DISCUSSION: These results show that OCT-A
can be used as an interesting addition in the diagnosis of CNV in nAMD. All CNV
could be visualized using OCT-A and especially classical CNV could be clearly
recognized in most cases. In contrast occult CNV could be identified in slightly
fewer cases.
PMID- 28707093
TI - Comment on "CIRSE Guidelines on Percutaneous Needle Biopsy (PNB)".
PMID- 28707094
TI - Primary and Secondary Percutaneous Ureteral Stent Placement: Comparison of Stent
Patency and Clinical Outcome.
AB - OBJECTIVES: To compare early double J ureteral stent (DJUS) dysfunction rate and
long-term patency between two percutaneous ureteral stent placement methods:
single-stage (primary) or two-stage (secondary) procedures. METHODS: A total of
250 (176 primary and 74 secondary) DJUS placements performed on interventional
unit were retrospectively reviewed between February 2008 and March 2014. Early
DJUS dysfunction was defined as no passage of contrast media into the urinary
bladder in 2-3 days after placement. Long-term patency was considered if the
ureteral stent functioned for 3 months (time point for a first routine DJUS
change). Amount of blood retained in the collecting system was scored on
nephrostogram immediately after DJUS placement with three levels of score.
RESULTS: The overall early DJUS dysfunction rate and long-term patency rate were
30.8 and 96.7%. The early DJUS dysfunction rates were similar in primary and
secondary DJUS placements (30.7 and 31.1%, P = 0.950). The long-term patency
rates were similar in primary and secondary groups (96.2 and 97.9%, P = 0.928).
The amount of blood retained in the collecting system between primary and
secondary groups was not significantly different. The early DJUS dysfunction rate
significantly increased with increasing blood retention. CONCLUSIONS: The early
DJUS dysfunction rates and long-term patency are similar in primary and secondary
DJUS placement. However, the early DJUS dysfunction rate can be increased by
increasing the blood retention in the collecting system.
PMID- 28707092
TI - The determinants of alternative RNA splicing in human cells.
AB - Alternative splicing represents an important level of the regulation of gene
function in eukaryotic organisms. It plays a critical role in virtually every
biological process within an organism, including regulation of cell division and
cell death, differentiation of tissues in the embryo and the adult organism, as
well as in cellular response to diverse environmental factors. In turn, studies
of the last decade have shown that alternative splicing itself is controlled by
different mechanisms. Unfortunately, there is no clear understanding of how these
diverse mechanisms, or determinants, regulate and constrain the set of
alternative RNA species produced from any particular gene in every cell of the
human body. Here, we provide a consolidated overview of alternative splicing
determinants including RNA-protein interactions, epigenetic regulation via
chromatin remodeling, coupling of transcription-to-alternative splicing, effect
of secondary structures in pre-RNA, and function of the RNA quality control
systems. We also extensively and critically discuss some mechanistic insights on
coordinated inclusion/exclusion of exons during the formation of mature RNA
molecules. We conclude that the final structure of RNA is pre-determined by a
complex interplay between cis- and trans-acting factors. Altogether, currently
available empirical data significantly expand our understanding of the
functioning of the alternative splicing machinery of cells in normal and
pathological conditions. On the other hand, there are still many blind spots that
require further deep investigations.
PMID- 28707095
TI - Chronic administration of myristic acid improves hyperglycaemia in the Nagoya
Shibata-Yasuda mouse model of congenital type 2 diabetes.
AB - AIMS/HYPOTHESIS: Previously, we demonstrated that myristic acid (14:0) increases
levels of diacylglycerol kinase (DGK) delta, a key enzyme involved in type 2
diabetes exacerbation, and enhances glucose uptake in C2C12 myotube cells.
Moreover, results from a population-based cohort study suggest that consumption
of high-fat dairy products, which contain high amounts of myristic acid, is
associated with a lower risk of developing type 2 diabetes. Taken together, we
hypothesised that intake of myristic acid reduces type 2 diabetes risk in vivo.
The aim of this study was to examine the glucose-lowering effect of myristic acid
in Nagoya-Shibata-Yasuda (NSY) mice, a spontaneous model for studying obesity
related type 2 diabetes. METHODS: Male NSY mice were orally administered vehicle
(n = 9), 300 mg/kg of myristic acid (n = 14) or 300 mg/kg of palmitic acid (16:0)
(n = 9) every other day from 4 weeks of age. Glucose and insulin tolerance tests
were performed at weeks 18, 24 and 30, and weeks 20 and 26, respectively.
DGKdelta levels were measured in skeletal muscle from 32-36-week-old NSY mice via
western blot. RESULTS: Chronic oral administration of myristic acid ameliorated
glucose tolerance (24-28% decrease in blood glucose levels during glucose
tolerance tests) and reduced insulin-responsive blood glucose levels (~20%
decrease) in male NSY mice compared with vehicle and palmitic acid groups at 24
30 weeks of age (the age at which the severity of type 2 diabetes is exacerbated
in NSY mice). Myristic acid also attenuated the increase in body weight seen in
NSY mice. Furthermore, the fatty acid increased DGKdelta levels (~1.6-fold) in
skeletal muscle of NSY mice. CONCLUSIONS/INTERPRETATION: These results suggest
that the chronic oral administration of myristic acid improves hyperglycaemia by
decreasing insulin-responsive glucose levels and reducing body weight, and that
the fatty acid accounts for the diabetes protective properties of high-fat dairy
products. Myristic acid is a potential candidate for the prevention and treatment
of type 2 diabetes mellitus and its related diseases.
PMID- 28707096
TI - [Medical quality standards for selected urological aids and devices : Consensus
for patients with neurogenic urinary bladder dysfunction].
AB - BACKGROUND: Using the CE mark of therapeutic appliances is, on its own, not
sufficient enough for their appropriate and effective application. In order to
treat the patient successfully, not jeopardizing the success of the treatment,
medical quality criteria for therapeutic appliances care are necessary to
acceptably compensate for a patient's disabilities. OBJECTIVES: Medical quality
criteria are formulated for the most frequently used urological aids and devices,
considering hygienic requirements, international literature and the practical
experience of physicians and nurses with regard to the care of patients with
neurogenic urinary bladder dysfunction. METHODS: An expert group of urologists,
surgeons, rehabilitation physicians and nurses has developed medical quality
criteria via a structured consensus procedure. Developing these criteria, the
group has taken into account current jurisprudence, the current resource
directory of neurourological relevant aids, data from international literature
and hygiene requirements. RESULTS: Medical quality requirements are discussed and
defined for selected groups of urological devices (single use catheters,
indwelling catheters, external catheters, urine bags, templates and diapers as
well as devices for the electrostimulation of nerves). CONCLUSION: The presented
quality requirements offer the possibility to stabilize quality of care with
neurourological relevant therapeutic appliances. The catalogue of therapeutic
appliances must be urgently updated. Urinal catheters for single use must be
classified as an individual product group. Devices for anterior root stimulation
and neuromodulation must be included in the resource directory. The incontinence
severity classification needs to be reviewed.
PMID- 28707097
TI - [Rare tumor as a cause for urinary retention].
PMID- 28707098
TI - Creating Environments to Support Breastfeeding: The Challenges and Facilitators
of Policy Development in Hospitals, Clinics, Early Care and Education, and
Worksites.
AB - Objectives Supportive organizational breastfeeding policies can establish
enabling environments for breastfeeding. In this qualitative study we identify
facilitators and barriers to the development, adoption, and implementation of
supportive breastfeeding policies and practices in four influential sectors for
breastfeeding women: hospitals, clinics, early care and education settings, and
worksites. Methods We interviewed 125 individuals representing 110 organizations
in Washington State about their breastfeeding policy development and
implementation process between August 2014 and February 2015. Greenhalgh's
diffusion of innovations framework guided the interviews and qualitative
analysis. Results Breastfeeding policy facilitators across the sectors include
national and state laws and regulations, performance tracking requirements, and
an increasingly supportive sociopolitical climate; barriers include limited
resources and appreciation about the need for breastfeeding policies, and certain
organizational characteristics such as workforce age. Despite broad support for
breastfeeding, organizations differed on perceptions about the usefulness of
written breastfeeding policies. Personal breastfeeding experiences of policy
makers and staff affect organizational breastfeeding policies and practices.
Conclusions for Practice Supportive organizational systems and environments are
built through effective policy development processes; public health can support
breastfeeding policy development and assure a coordinated continuum of care by
leveraging federal health care policy requirements, building networks to support
training and collaboration, and disseminating strategies that reflect the
personal nature of breastfeeding.
PMID- 28707099
TI - Maternal Health Care Utilization Among Syrian Refugees in Lebanon and Jordan.
AB - Purpose The influx of Syrian refugees into Jordan and Lebanon over the last 5
years presents an immense burden to national health systems. This study was
undertaken to assess utilization of maternal health services among Syrian
refugees in both countries. Description A cross-sectional survey of Syrian
refugees living in urban and rural (non-camp) settings was conducted using a two
stage cluster survey design with probability proportional to size sampling in
2014-2015. Eighty-six percent of surveyed households in Lebanon and 88% of
surveyed households in Jordan included women with a live birth in the last year.
Information from women in this sub-set of households was analyzed to understand
antenatal and intrapartum health service utilization. Assessment A majority of
respondents reported seeking antenatal care, 82% and 89% in Jordan and Lebanon,
respectively. Women had an average of at least six antenatal care visits. Nearly
all births (98% in Jordan and 94% in Lebanon) took place in a health facility.
Cesarean rates were similar in both countries; approximately one-third of all
births were cesarean deliveries. A substantial proportion of women incurred costs
for intrapartum care; 33% of Syrian women in Jordan and 94% of Syrian women in
Lebanon reported paying out of pocket for their deliveries. The proportion of
women incurring costs for intrapartum care was higher in Jordan both countries
for women with cesarean deliveries compared to those with vaginal deliveries;
however, this difference was not statistically significant in either country
(Jordan p-value = 0.203; Lebanon p-value = 0.099). Conclusion Syrian refugees
living in Jordan and Lebanon had similar levels of utilization of maternal health
services, despite different health systems and humanitarian assistance
provisions. As expected, a substantial proportion of households incurred out-of
pocket costs for essential maternal and newborn health services, making cost a
major factor in care-seeking decisions and locations. As health financing
policies shift to account for the continued burden of refugee hosting on the
health system, sustained attention to the availability and quality of essential
maternal and newborn health services is needed to protect both refugee and host
populations women's rights to health and health care during pregnancy,
childbirth, and the postpartum period.
PMID- 28707100
TI - Improving Safe Sleep Modeling in the Hospital through Policy Implementation.
AB - Introduction Sleep-related infant deaths are major contributors to Tennessee's
high infant mortality rate. The purpose of this initiative was to evaluate the
impact of policy-based efforts to improve modeling of safe sleep practices by
health care providers in hospital settings across Tennessee. Methods Safe sleep
policies were developed and implemented at 71 hospitals in Tennessee. Policies,
at minimum, were required to address staff training on the American Academy of
Pediatrics' safe sleep recommendations, correct modeling of infant safe sleep
practices, and parent education. Hospital data on process measures related to
training and results of crib audits were compiled for analysis. Results The
overall observance of infants who were found with any risk factors for unsafe
sleep decreased 45.6% (p <= 0.001) from the first crib audit to the last crib
audit. Significant decreases were noted for specific risk factors, including
infants found asleep not on their back, with a toy or object in the crib, and not
sleeping in a crib. Significant improvements were observed at hospitals where
printed materials or video were utilized for training staff compared to face-to
face training. Discussion Statewide implementation of the hospital policy
intervention resulted in significant reductions in infants found in unsafe sleep
situations. The most common risk factors for sleep-related infant deaths can be
modeled in hospitals. This effort has the potential to reduce sleep-related
infant deaths and ultimately infant mortality.
PMID- 28707101
TI - The Use of ACOG Guidelines: Perceived Contraindications to IUD and Implant Use
Among Family Planning Providers.
AB - Objectives The uptake and actual use of the current guidelines from the American
College of Obstetrics and Gynecology (ACOG) is unknown. Methods Family planning
providers across Colorado and Iowa were surveyed as part of statewide initiatives
to reduce unintended pregnancy in 2010 and 2012, both before and after the
release of the guidelines. These initiatives focused on the promotion of
intrauterine devices (IUDs) and implants. These surveys included questions on
providers' views regarding the suitability and safety of the copper T IUD,
hormonal IUD, and single rod implant for various subgroups of clients. The
results are contrasted with guidelines provided in July of 2011 by ACOG. This
strategy provides both baseline and follow-up models about the methods promoted
in these guidelines. Results Findings show that there is some improvement in
beliefs that IUDs are suitable and safe for women who are post-partum, post
abortion, have had an ectopic pregnancy, are nulliparous, teenagers, or have a
history of STIs. However, these clinicians' views are not entirely in alignment
with ACOG recommendations in their beliefs that these methods should not be used
immediately post-partum or post-abortion. Notable percentages of these clinicians
were hesitant to recommend these effective methods for other groups of patients,
approved for use by ACOG. Conclusions While the cost of these methods is a
barrier to adoption, these data suggest that there are continuing provider
barriers to their use as well. The paper concludes with suggestions for further
training for family planning providers.
PMID- 28707102
TI - Perceptions and Practices Related to Obesity in Adolescent Students and Their
Programmatic Implications: Qualitative Evidence from Ho Chi Minh City, Vietnam.
AB - Background Prevalence of obesity in children in Ho Chi Minh City is rising in the
last 10 years. We conducted a formative study to explore the perceptions and
practices related to obesity, diet and physical activity among the students in
two junior high schools in two suburbs in Ho Chi Minh City to aid in the design
of an intervention in preventing obesity among adolescent school children. Method
We conducted in-depth interviews with twenty participants including students,
their parents, physical education teachers and a representative of the Department
of Education. Manually coded and organized data were analysed applying a thematic
analysis approach to divulge trends, diversities and similarities among the
emerging themes. Results The study revealed diversified perceptions of obesity,
diet and physical activity and their relationship with adolescent obesity. The
findings indicated low practice of physical activity among almost all students
who participated in the study. The major barriers to obesity prevention included
knowledge gaps, food environment in the school, devaluation of physical activity
and academic burden. Conclusion The findings provide contextual insights to
design a culturally appropriate and feasible intervention to tackle child and
adolescent obesity by harnessing the perspectives of the target populations.
PMID- 28707103
TI - Examination of Routine Use of Prenatal Weight Gain Charts as a Communication Tool
for Providers.
AB - Objectives In 2009 the IOM revised prenatal weight gain guidelines. The primary
purpose of this pilot study was to assess if provider education and use of
prenatal weight gain charts to track weight gain and counsel patients was
associated with better patient and provider knowledge and communication about the
guidelines. Methods A prospective non-randomized study conducted in four OB
practices (two control, two intervention). Data sources included provider surveys
(n = 16 intervention, 21 control), patient surveys (n = 332), and medical
records. Intervention clinics received provider education on the IOM guidelines
and used patient education materials and prenatal weight gain charts to track
weight gain and as a counseling tool. Comparison clinics received no education
and did not use the charts or patient education information. Results More
patients at intervention clinics (92.3%) reported that a provider gave them
advice about weight gain, compared to patients from comparison clinics (66.4%) (p
< 0.001). Intervention patients were also more likely to report satisfaction
discussions with their provider about weight gain (83.1 vs. 64.3%, p = 0.007).
Intervention clinic patients were more likely to have knowledge of the guidelines
indicated by 72.3% reporting a target weight gain amount within the guidelines
versus 50.4% of comparison patients (p < 0.001). Conclusion Provider education
and use of weight gain charts resulted in higher patient reported communication
about weight gain from their provider, higher patient satisfaction with those
discussions, and better knowledge of the appropriate target weight gain goals.
PMID- 28707104
TI - Microbial Hydrocarbon Formation from Biomass.
AB - Fossil carbon sources mainly contain hydrocarbons, and these are used on a huge
scale as fuel and chemicals. Producing hydrocarbons from biomass instead is
receiving increased attention. Achievable yields are modest because oxygen atoms
need to be removed from biomass, keeping only the lighter carbon and hydrogen
atoms. Microorganisms can perform the required conversions, potentially with high
selectivity, using metabolic pathways that often end with decarboxylation.
Metabolic and protein engineering are used successfully to achieve hydrocarbon
production levels that are relevant in a biorefinery context. This has led to
pilot or demo processes for hydrocarbons such as isobutene, isoprene, and
farnesene. In addition, some non-hydrocarbon fermentation products are being
further converted into hydrocarbons using a final chemical step, for example,
ethanol into ethene. The main advantage of direct microbial production of
hydrocarbons, however, is their potentially easy recovery because they do not
dissolve in fermentation broth.
PMID- 28707105
TI - Mobile applications for colorectal surgery journals: Do we really need them?
PMID- 28707106
TI - Robotic transanal surgery (RTAS) with utilization of a next-generation single
port system: a cadaveric feasibility study.
AB - PURPOSE: Transanal surgery remains both an innovative approach to rectal
pathology and a demonstrated technical challenge. Improved technology using a
single-port system robotic platform (SPS) offers a promising option for this
surgery. METHODS: SPS robotic system was utilized to perform submucosal, full
thickness and cylindrical excision on four cadavers. Operative performance and
surgeon fatigue were measured. RESULTS: On all types of resections, the SPS
system performed well. There were no piecemeal or fragmented resections. Closure
was judged to be good to excellent in all cases. Surgeon assessment of setup and
performance of the SPS was excellent in all cases. CONCLUSIONS: SPS robotic
transanal surgery represents an exciting new option for transanal surgery.
PMID- 28707107
TI - The Objective Assessment of Cough Frequency in Bronchiectasis.
AB - INTRODUCTION: Cough in bronchiectasis is associated with significant impairment
in health status. This study aimed to quantify cough frequency objectively with a
cough monitor and investigate its relationship with health status. A secondary
aim was to identify clinical predictors of cough frequency. METHODS: Fifty-four
patients with bronchiectasis were compared with thirty-five healthy controls.
Objective 24-h cough, health status (cough-specific: Leicester Cough
Questionnaire LCQ and bronchiectasis specific: Bronchiectasis Health
Questionnaire BHQ), cough severity and lung function were measured. The clinical
predictors of cough frequency in bronchiectasis were determined in a multivariate
analysis. RESULTS: Objective cough frequency was significantly raised in patients
with bronchiectasis compared to healthy controls [geometric mean (standard
deviation)] 184.5 (4.0) vs. 20.6 (3.2) coughs/24-h; mean fold-difference (95%
confidence interval) 8.9 (5.2, 15.2); p < 0.001 and they had impaired health
status. There was a significant correlation between objective cough frequency and
subjective measures; LCQ r = -0.52 and BHQ r = -0.62, both p < 0.001. Sputum
production, exacerbations (between past 2 weeks to 12 months) and age were
significantly associated with objective cough frequency in multivariate analysis,
explaining 52% of the variance (p < 0.001). There was no statistically
significant association between cough frequency and lung function. CONCLUSIONS:
Cough is a common and significant symptom in patients with bronchiectasis. Sputum
production, exacerbations and age, but not lung function, were independent
predictors of cough frequency. Ambulatory objective cough monitoring provides
novel insights and should be further investigated as an outcome measure in
bronchiectasis.
PMID- 28707108
TI - Clinical and Biological Insights from the University of California San Francisco
Prospective and Longitudinal Cohort.
AB - INTRODUCTION: Sarcoidosis is a systemic inflammatory disease characterized by non
necrotizing granulomas in involved organs, most commonly the lung. Description of
patient characteristics in the Western United States is limited. Furthermore,
blood-based measures that relate to clinical sarcoidosis phenotypes are lacking.
We present an analysis of a prospective, longitudinal sarcoidosis cohort at a
Northern Californian academic medical center. METHODS: We enrolled 126
sarcoidosis subjects and 64 healthy controls and recorded baseline demographic
and clinical characteristics. We used regression models to identify factors
independently associated with pulmonary physiology. We tested whether blood
transcript levels at study entry could relate to longitudinal changes in
pulmonary physiology. RESULTS: White, non-Hispanics composed ~70% of subjects.
Hispanics and Blacks had a diagnostic biopsy at an age ~7 years younger than
whites. Obstructive, but not restrictive, physiology characterized Scadding Stage
IV patients. Subjects reporting use of immunosuppression had worse FEV1%p, FVC%p,
and DLCO%p compared to subjects never treated, regardless of Scadding stage. We
defined sarcoidosis disease activity by a drop in pulmonary function over 36
months and found that subjects meeting this definition had significant repression
of blood gene transcripts related to T cell receptor signaling pathways, referred
to as the "TCR factor." CONCLUSION: Obstructive pulmonary physiology defined
Stage IV patients which were mostly white, non-Hispanics. Genes comprising the
composite gene expression score, TCR factor, may represent a blood-derived
measure of T-cell activity and an indirect measure of active sarcoidosis
inflammation. Validation of this measure could translate into individualized
treatment for sarcoidosis patients.
PMID- 28707109
TI - The Assessment of Cough in a Sarcoidosis Clinic Using a Validated instrument and
a Visual Analog Scale.
AB - PURPOSE: Cough is a common symptom of pulmonary sarcoidosis. We analyzed the
severity of cough and factors associated with cough in a university sarcoidosis
clinic cohort. METHODS: Consecutive patients completed the Leicester Cough
Questionnaire (LCQ) and a cough visual analog scale (VAS). Clinical and
demographic data were collected. Means of the LCQ were analyzed in patients who
had multiple visits in terms of constant variables (e.g., race, sex). RESULTS:
355 patients completed the LCQ and VAS at 874 visits. Cough was significantly
worse in blacks than whites as determined by the LCQ-mean (16.5 +/- 2.6 vs. 17.8
+/- 3.0, p < 0.001) and VAS-mean (3.8 +/- 3.0 vs. 2.0 +/- 2.6, p < 0.0001). Cough
was worse in women than men as measured by the VAS-mean (2.7 +/- 2.9 vs. 2.2 +/-
2.7, p = 0.002), one of the LCQ-mean domains (LCQ-Social-mean 5.4 +/- 0.9 vs. 5.2
+/- 1.0, p = 0.03), but not the total LCQ-mean score. Cough was not significantly
different by either measure in terms of smoking status, age, or spirometric
parameter (FVC % predicted, FEV1 % predicted, FEV1/FVC). In a multivariable
linear regression analysis, cough was significantly worse in blacks than whites
and in pulmonary sarcoidosis than non-pulmonary sarcoidosis with both cough
measures, in women than men for the VAS only, and not for spirometric parameters,
Scadding stage, or age. The LCQ and VAS were strongly correlated. CONCLUSIONS: In
a large university outpatient sarcoidosis cohort, cough was worse in blacks than
whites. Cough was not statistically significantly different in terms of age,
spirometric measures, Scadding stage, or smoking status. The LCQ correlated
strongly with a visual analog scale for cough.
PMID- 28707110
TI - What Factors are Associated With 90-day Episode-of-care Payments for Younger
Patients With Total Joint Arthroplasty?
AB - BACKGROUND: Total joint arthroplasty (TJA) has been identified as a procedure
with substantial variations in inpatient and postacute care payments. Most
studies in this area have focused primarily on the Medicare population and rarely
have characterized the younger commercially insured populations. Understanding
the inpatient and postdischarge care service-component differences across 90-day
episodes of care and factors associated with payments for younger patients is
crucial for successful implementation of bundled payments in TJA in non-Medicare
populations. PURPOSE: (1) To assess the mean total payment for a 90-day primary
TJA episode, including the proportion attributable to postdischarge care, and (2)
to evaluate the role of procedure, patient, and hospital-level factors associated
with 90-day episode-of-care payments in a non-Medicare patient population younger
than 65 years. METHOD: Claims data for 2008 to 2013 from Blue Cross Blue Shield
of Texas were obtained for primary TJAs. A total of 11,131 procedures were
examined by aggregating payments for the index hospital stay and any postacute
care including rehabilitation services and unplanned readmissions during the 90
day postdischarge followup period. A three-level hierarchical model was developed
to determine procedure-, patient-, and hospital-level factors associated with 90
day episode-of-care payments. RESULTS: The mean total payment for a 90-day
episode for TJA was USD 47,700 adjusted to 2013 USD. Only 14% of 90-day episode
payments in our population was attributable to postdischarge-care services, which
is substantially lower than the percentage estimated in the Medicare population.
A prolonged length of stay (rate ratio [RR], 1.19; 95% CI, 1.15-1.23; p <=
0.001), any 90-day unplanned readmission (RR, 1.64; 95% CI, 1.57-1.71; p <=
0.001), computer-assisted surgery (RR, 1.031; 95% CI, 1.004-1.059; p <= 0.05),
initial home discharge with home health component (RR, 1.029; 95% CI, 1.013
1.046; p <= 0.001), and very high patient morbidity burden (RR, 1.105; 95% CI,
1.062-1.150; p <= 0.001) were associated with increased TJA payments. Hospital
level factors associated with higher payments included urban location (RR, 1.29;
95% CI, 1.17-1.42; p <= 0.001), lower hospital case mix based on average relative
diagnosis related group weight (RR, 0.94; 95% CI, 0.89-0.95; p <= 0.001), and
large hospital size as defined by total discharge volume (RR, 1.082; 95% CI,
1.009-1.161; p <= 0.05). All procedure, patient, and hospital characterizing
factors together explained 11% of variation among hospitals and 49% of variation
among patients. CONCLUSION: Inpatient care contributed to a much larger
proportion of total payments for 90-day care episodes for primary TJA in our
younger than 65-year-old commercially insured population. Thus, inpatient care
will continue to be an essential target for cost-containment and delivery
strategies. A high percentage of hospital-level variation in episode payments
remained unexplained by hospital characteristics in our study, suggesting system
inefficiencies that could be suitable for bundling. However, replication of this
study among other commercial payers in other parts of the country will allow for
conclusions that are more robust and generalizable. LEVEL OF EVIDENCE: Level II,
economic analysis.
PMID- 28707111
TI - Limiting the cost of mutualism: the defensive role of elongated gynophore in the
leafflower-moth mutualism.
AB - Mutualisms are interactions from which both partners benefit but may collapse if
mutualists' costs and benefits are not aligned. Host sanctions are one mechanism
whereby hosts selectively allocate resources to the more cooperative partners and
thereby reduce the fitness of overexploiters; however, many mutualisms lack
apparent means of host sanctions. In mutualisms between plants and pollinating
seed parasites, such as those between leafflowers and leafflower moths,
pollinators consume subsets of the seeds as larval food in return for their
pollination service. Plants may select against overexploiters by selectively
aborting flowers with a heavy egg load, but in many leafflower species, seeds are
fully eaten in some fruits, suggesting that such a mechanism is not present in
all species. Instead, the fruits of Breynia vitis-idaea have stalk-like
structures (gynophore) through which early-instar moth larvae must bore to reach
seeds. Examination of moth mortality in fruits with different gynophore lengths
suggested that fruits with longer gynophore had higher moth mortality and,
therefore, less seed damage. Most moth mortality occurred at the egg stage or as
early larval instar before moths reached the seeds, consistent with the view that
gynophore functions to prevent moth access to seeds. Gynophore length was
unaffected by plant size, extent of moth oviposition, or geography; thus, it is
most likely genetically controlled. Because gynophores do not elongate in related
species whose pollinators oviposit directly into the ovary, the gynophore in B.
vitis-idaea may have evolved as a defense to limit the cost of the mutualism.
PMID- 28707112
TI - Disease-associated change in an amphibian life-history trait.
AB - Emerging pathogens can drive evolutionary shifts in host life-history traits, yet
this process remains poorly documented in vertebrate hosts. Amphibian
chytridiomycosis, caused by infection with the fungal pathogen Batrachochytrium
dendrobatidis (Bd), is the worst recorded wildlife disease and has caused the
extinction of over 100 species across multiple continents. A similar number of
additional species have experienced mass declines and Bd remains a major source
of mortality in many populations of declined species now persisting with the
pathogen. Life-history theory predicts that increased extrinsic mortality in Bd
infected populations may alter amphibian life-history traits, but this has not
been examined. Here, we investigate whether population Bd status is associated
with age and size at maturity by comparing long-exposed Bd-infected populations,
Bd-free populations, and museum specimens collected prior to Bd emergence for the
endangered Australian frog Litoria verreauxii alpina. We show that Bd-infected
populations have a higher proportion of males that mature at 1 year of age, and
females that mature at 2 years of age, compared to Bd-free populations. Earlier
maturation was associated with reduced size at maturity in males. Consistent with
life-history theory, our findings may represent an adaptive evolutionary shift
towards earlier maturation in response to high Bd-induced mortality. To our
knowledge, this study provides the first evidence for a post-metamorphic Bd
associated shift in an amphibian life-history trait. Given high mortality in
other Bd-challenged species, we suggest that chytridiomycosis may be a
substantial new selection pressure shaping life-history traits in impacted
amphibian species across multiple continents.
PMID- 28707113
TI - Genetically engineered hairy root cultures of Hyoscyamus senecionis and H.
muticus: ploidy as a promising parameter in the metabolic engineering of tropane
alkaloids.
AB - KEY MESSAGE: Tetraploidy improves overexpression of h6h and scopolamine
production of H. muticus, while in H. senecionis, pmt overexpression and
elicitation can be used as effective methods for increasing tropane alkaloids.
The effects of metabolic engineering in a polyploid context were studied by
overexpression of h6h in the tetraploid hairy root cultures of H. muticus. Flow
cytometry analysis indicated genetic stability in the majority of the clones,
while only a few clones showed genetic instability. Among all the diploid and
tetraploid clones, the highest level of h6h transgene expression and scopolamine
accumulation was interestingly observed in the tetraploid clones of H. muticus.
Therefore, metabolic engineering of the tropane biosynthetic pathway in
polyploids is suggested as a potential system for increasing the production of
tropane alkaloids. Transgenic hairy root cultures of Hyoscyamus senecionis were
also established. While overexpression of pmt in H. senecionis was correlated
with a sharp increase in hyoscyamine production, the h6h-overexpressing clones
were not able to accumulate higher levels of scopolamine than the leaves of
intact plants. Applying methyl jasmonate was followed by a sharp increase in the
expression of pmt and a drop in the expression of tropinone reductase II (trII)
which consequently resulted in the higher biosynthesis of hyoscyamine and total
alkaloids in H. senecionis.
PMID- 28707114
TI - The Shoulder Instability-Return to Sport after Injury (SIRSI): a valid and
reproducible scale to quantify psychological readiness to return to sport after
traumatic shoulder instability.
AB - PURPOSE: The main goal of this study was to propose and validate a tool to
quantify the psychological readiness of athletes to return to sport following
traumatic shoulder instability and conservative or surgical management. METHODS:
"Knee" was replaced by the term "shoulder" in the Anterior Cruciate Ligament
Return to Sport after Injury scale. This pilot test of the Shoulder Instability
Return to Sport after Injury scale (SIRSI) was performed in a group of athletes
who underwent surgery for post-traumatic chronic anterior shoulder instability.
The final version was then validated according to the international COSMIN
methodology. A retrospective study was performed including all rugby players who
had reported an episode of instability between 2012 and 2013. The WOSI and the
Walch-Duplay scales were used as reference questionnaires. RESULTS: Sixty-two
patients were included, mean age 26 +/- 5.2 years old, 5 women/57 men. Patients
were professional or competitive athletes (70.9%) and followed-up for 4.6 +/- 1.6
years after the first episode of shoulder instability. Shoulder surgery was
performed in 30/62 (48.4%) patients, a mean 1.6 +/- 1.2 years after the first
episode of instability. The SIRSI was strongly correlated with the reference
questionnaires (r = 0.80, p < 10-5). The mean SIRSI score was significantly
higher in patients who returned to play rugby (60.9 +/- 26.6% vs 38.1 +/- 25.6%,
p = 0.001). The internal consistency of the scale was high (alpha = 0.96).
Reproducibility of the test-retest was excellent (rho = 0.93, 95% CI [0.89-0.96],
p < 10-5). No ceiling/floor effects were found. CONCLUSION: The SIRSI is a valid,
reproducible scale that identifies patients who are ready to return to the same
sport after an episode of shoulder instability, whether they undergo surgery or
not. LEVEL OF EVIDENCE: III.
PMID- 28707115
TI - Preoperative magnetic resonance imaging predicts eligibility for arthroscopic
primary anterior cruciate ligament repair.
AB - PURPOSE: To assess the role of preoperative magnetic resonance imaging (MRI) on
the eligibility for arthroscopic primary anterior cruciate ligament (ACL) repair.
METHODS: All patients undergoing ACL surgery between 2008 and 2017 were included.
Patients underwent arthroscopic primary repair if sufficient tissue length and
quality were present, or they underwent single-bundle ACL reconstruction.
Preoperative MRI tear locations were graded with the modified Sherman
classification: type I (>90% distal remnant length), type II (75-90%), or type
III (25-75%). MRI tissue quality was graded as good, fair, or poor. Arthroscopy
videos were reviewed for tissue length and quality, and final treatment. RESULTS:
Sixty-three repair patients and 67 reconstruction patients were included. Repair
patients had more often type I tears (41 vs. 4%, p < 0.001) and good tissue
quality (89 vs. 12%, p < 0.001). Preoperative MRI tear location and tissue
quality predicted eligibility for primary repair: 90% of all type I tears and 88%
of type II tears with good tissue quality were repaired, while only 23% of type
II tears with fair tissue quality, 0% of type II tears with poor tissue quality,
and 14% of all type III tears could be repaired. CONCLUSIONS: This study showed
that tear location and tissue quality on preoperative MRI can predict eligibility
for arthroscopic primary ACL repair. These findings may guide the orthopaedic
surgeon on the preoperative assessment for arthroscopic primary repair of
proximal ACL tears. LEVEL OF EVIDENCE: Level IV.
PMID- 28707116
TI - Rotator cuff degeneration of the healthy shoulder in patients with unilateral arm
amputation is not worsened by overuse.
AB - PURPOSE: In order to evaluate whether overuse has a significant role in rotator
cuff tear (RCT) aetiology, we evaluated both shoulders of patients with old
unilateral arm amputation expecting a higher rate of RC degeneration in the
healthy side. METHODS: Nineteen males and six females (mean age: 57.3 +/- 10.1)
with an old (>20 years) unilateral arm amputation were submitted to an MRI of
both shoulders. Tendon status and muscle tropism were evaluated according to
Sugaya and Fuchs classifications, respectively; the acromion humeral distance was
measured. Statistical analysis was performed to verify the prevalence of Sugaya
and Fuchs categories in each sides. RESULTS: A significant prevalence of Sugaya
type II in the amputated side (p = 0.02) and of type I in the healthy side (p <
0.001) was found. Rotator cuff was healthy in 28 and 52% of amputated and non
amputated side, respectively. The mean acromio-humeral distances of the amputated
and healthy side were 0.8 cm (SD: 0.1) and 0.9 cm (SD: 0.1), respectively, (p =
0.02). A significant prevalence of Fuchs type II category in the healthy side (p
< 0.001) was found. Fuchs III/IV were observed in 40 and 12% of amputated and
healthy side, respectively. CONCLUSIONS: The present study resizes the role of
overuse on the aetiology of RCT. Cuff tear prevalence in not amputated shoulders,
inevitably submitted to functional overload, was not higher than that of
coetaneous subjects with two functional upper limbs. Shoulder non-use is a risk
factor for rotator cuff tear. As the prevalence of rotator cuff degeneration/tear
is higher in the amputee side, non-use is a more relevant risk factor than
overuse. In the daily clinical practice, patients with rotator cuff tear should
be encouraged to shoulder movement because rotator cuff tendon status could be
worsened by disuse. LEVEL OF EVIDENCE: III.
PMID- 28707117
TI - Erratum to: Relaxation of the MCL after an Open-Wedge High Tibial Osteotomy
results in decreasing contact pressures of the knee over time.
PMID- 28707118
TI - Exemplars, ethics, and illness narratives.
AB - Many people report that reading first-person narratives of the experience of
illness can be morally instructive or educative. But although they are ubiquitous
and typically sincere, the precise nature of such educative experiences is
puzzling, for those narratives typically lack the features that modern
philosophers regard as constitutive of moral reason. I argue that such puzzlement
should disappear, and the morally educative power of illness narratives
explained, if one distinguishes two different styles of moral reasoning: an
inferentialist style that generates the puzzlement and an alternative exemplarist
style that offers a compelling explanation of the morally educative power of
pathographic literature.
PMID- 28707119
TI - Response to the letter by Adams and Kwee, entitled: "Unproven value of end-of
treatment FDG-PET in Hodgkin lymphoma".
PMID- 28707120
TI - The ninth international congress of the Croatian Society of Nuclear Medicine -
Rovinj, May 04-07, 2017.
PMID- 28707121
TI - Unproven value of end-of-treatment FDG-PET in Hodgkin lymphoma.
PMID- 28707122
TI - Segond's fracture: a biomechanical cadaveric study using navigation.
AB - BACKGROUND: Segond's fracture is a well-recognised radiological sign of an
anterior cruciate ligament (ACL) tear. While previous studies evaluated the role
of the anterolateral ligament (ALL) and complex injuries on rotational stability
of the knee, there are no studies on the biomechanical effect of Segond's
fracture in an ACL deficient knee. The aim of this study was to evaluate the
effect of a Segond's fracture on knee rotation stability as evaluated by a
navigation system in an ACL deficient knee. MATERIALS AND METHODS: Three
different conditions were tested on seven knee specimens: intact knee, ACL
deficient knee and ACL deficient knee with Segond's fracture. Static and dynamic
measurements of anterior tibial translation (ATT) and axial tibial rotation (ATR)
were recorded by the navigation system (2.2 OrthoPilot ACL navigation system B.
Braun Aesculap, Tuttlingen, Germany). RESULTS: Static measurements at 30 degrees
showed that the mean ATT at 30 degrees of knee flexion was 5.1 +/- 2.7 mm in the
ACL intact condition, 14.3 +/- 3.1 mm after ACL cut (P = 0.005), and 15.2 +/- 3.6
mm after Segond's fracture (P = 0.08). The mean ATR at 30 degrees of knee
flexion was 20.7 degrees +/- 4.8 degrees in the ACL intact condition, 26.9
degrees +/- 4.1 degrees in the ACL deficient knee (P > 0.05) and 30.9 degrees
+/- 3.8 degrees after Segond's fracture (P = 0.005). Dynamic measurements during
the pivot-shift showed that the mean ATT was 7.2 +/- 2.7 mm in the intact knee,
9.1 +/- 3.3 mm in the ACL deficient knee(P = 0.04) and 9.7 +/- 4.3 mm in the ACL
deficient knee with Segond's fracture (P = 0.07). The mean ATR was 9.6 degrees
+/- 1.8 degrees in the intact knee, 12.3 degrees +/- 2.3 degrees in the ACL
deficient knee (P > 0.05) and 19.1 degrees +/- 3.1 degrees in the ACL deficient
knee with Segond's lesion (P = 0.016). CONCLUSION: An isolated lesion of the ACL
only affects ATT during static and dynamic measurements, while the addition of
Segond's fracture has a significant effect on ATR in both static and dynamic
execution of the pivot-shift test, as evaluated with the aid of navigation.
PMID- 28707123
TI - Visual properties and memorising scenes: Effects of image-space sparseness and
uniformity.
AB - Previous studies have demonstrated that humans have a remarkable capacity to
memorise a large number of scenes. The research on memorability has shown that
memory performance can be predicted by the content of an image. We explored how
remembering an image is affected by the image properties within the context of
the reference set, including the extent to which it is different from its
neighbours (image-space sparseness) and if it belongs to the same category as its
neighbours (uniformity). We used a reference set of 2,048 scenes (64 categories),
evaluated pairwise scene similarity using deep features from a pretrained
convolutional neural network (CNN), and calculated the image-space sparseness and
uniformity for each image. We ran three memory experiments, varying the memory
workload with experiment length and colour/greyscale presentation. We measured
the sensitivity and criterion value changes as a function of image-space
sparseness and uniformity. Across all three experiments, we found separate
effects of 1) sparseness on memory sensitivity, and 2) uniformity on the
recognition criterion. People better remembered (and correctly rejected) images
that were more separated from others. People tended to make more false alarms and
fewer miss errors in images from categorically uniform portions of the image
space. We propose that both image-space properties affect human decisions when
recognising images. Additionally, we found that colour presentation did not yield
better memory performance over grayscale images.
PMID- 28707124
TI - Examining the Functional Category in Chinese-English Code-Switching: Evidence
from the Eye-Movements.
AB - To investigate the grammatical constraints of code-switching (CS hereafter) under
the disputes of the constraint-based account versus the constraint-free account,
the effects of functional category on CS have long been investigated in the
existing studies. Thus, the present study, by asking 47 participants to take part
in an eye-movement experiment, examined the potential effects of functional
category on Chinese-English CS. We found that differential switch costs at
varying code-switched conditions as well as robust switch effects that last from
the early to the late stage. The findings could tentatively give rise to the
theoretical predictions of the minimalist program, a representative of the
constraint-free account rather than the functional head constraint, a typical
representative of the constraint-based account. Moreover, such switch effects
might initiate from the early to the very late stage in terms of time-course of
CS processing.
PMID- 28707126
TI - Estrogen receptor alpha gene (ESR1) polymorphism and its interaction with smoking
and drinking contribute to susceptibility of systemic lupus erythematosus.
AB - The aim of this study is to investigate the association of estrogen receptor
alpha gene (ESR1) polymorphisms, additional gene-gene, and gene-environment
interaction with systemic lupus erythematosus (SLE) risk. SNPStats (available
online at http://bioinfo.iconcologia.net/SNPstats ) was used to investigate the
Hardy-Weinberg equilibrium (HWE) in controls and association between SNP and SLE
risk. Generalized multifactor dimensionality reduction (GMDR) was used to screen
the interactions among SNPs and environmental risk factors; SLE risk was
significantly higher in carriers of rs2234693 C allele than those with TT (TC +
CC versus TT), adjusted OR (95%CI) = 1.57 (1.21-2.06), and was also higher in
carriers of rs9340799 G allele than those with AA (AG + GG versus AA), adjusted
OR (95%CI) = 1.68 (1.24-2.13). However, we also find no association between
rs2228480 and SLE risk after covariates adjustment. We found a significant two
locus model (p = 0.0010) involving rs2234693 and smoking; the cross-validation
consistency of this model was 10/10, and the testing accuracy was 62.70%. Smokers
with TC or CC of rs2234693 genotype have the highest SLE risk, compared to never
smokers with TT of rs2234693 genotype, OR (95%CI) was 2.50 (1.65-3.42), after
covariates adjustment for gender, age, alcohol drinking, and BMI. We found that C
allele of rs2234693 and G allele of rs9340799 within ESR1 gene, their interaction
between rs2234693 and current smoking were all associated with increased SLE
risk.
PMID- 28707127
TI - Increased incidence of respiratory tract cancers in people living near Portland
cement plants in Korea.
AB - PURPOSE: Portland cement contains carcinogens such as chromium and free silica,
and hence, inhalation of cement dust can cause respiratory tract cancers. The
purpose of this study was to determine whether living near a cement plant
increases the risk of respiratory tract cancers. METHODS: The study population
consisted of 341,793 people, all of whom lived in administrative districts within
3-km radius of ten cement plants in Korea. The respiratory tract cancer incidence
data (International Classification of Diseases, ten revision code C00-C14 and C30
C34) for 2008-2012 were obtained from regional cancer registries. Standardized
incidence ratios (SIRs) for each cancer site in the respiratory tract were
calculated using an indirect standardization method. RESULTS: Compared with the
general Korean population, the incidence of lung and bronchus cancer (C33-C34)
was significantly higher in all subjects [SIR 1.15, 95% confidence interval (CI)
1.02-1.29] and especially in the men subjects (SIR 1.47, 95% CI 1.29-1.68) in our
study population. In addition, the incidence of larynx cancer in men (SIR 1.64,
95% CI 0.97-2.59) and salivary gland cancer in women (SIR 3.03, 95% CI 0.98-7.07)
living near cement plants was marginally increased. CONCLUSIONS: These results
suggest that environmental exposure to Portland cement dust is a risk factor for
respiratory tract cancers.
PMID- 28707128
TI - Thymectomy is a beneficial therapy for patients with non-thymomatous ocular
myasthenia gravis: a systematic review and meta-analysis.
AB - Ocular myasthenia gravis, an autoimmune disease, is characterized by extraocular
muscle weakness. Myasthenia gravis is closely associated with the functional
status of the thymus gland. The efficacy of thymectomy for non-thymomatous ocular
myasthenia gravis remains controversial. Here, we present the first systematic
review and meta-analysis of studies assessing the outcome of thymectomy in
patients with non-thymomatous ocular myasthenia gravis and found that the pooled
rate of complete stable remission was 0.5074 with considerable heterogeneity.
Furthermore, subgroup analysis showed that the efficacy of thymectomy differed
according to geographical location. Furthermore, thymectomy outcomes are better
in children than they are in adults. Thymectomy clearly represents an effective
treatment for patients with non-thymomatous ocular myasthenia gravis. However,
more multicenter, randomized, controlled clinical trials are now required to
confirm these conclusions.
PMID- 28707129
TI - Neurosyphilis combined with acute anterior thalamic infarction.
PMID- 28707130
TI - Safety and efficacy of Cerebrolysin in motor function recovery after stroke: a
meta-analysis of the CARS trials.
AB - This meta-analysis combines the results of two identical stroke studies (CARS-1
and CARS-2) assessing efficacy of Cerebrolysin on motor recovery during early
rehabilitation. Cerebrolysin is a parenterally administered neuropeptide
preparation approved for the treatment of stroke. Both studies had a prospective,
randomized, double-blind, placebo-controlled design. Treatment with 30 ml
Cerebrolysin once daily for 3 weeks was started 24-72 h after stroke onset. In
addition, patients participated in a standardized rehabilitation program for 21
days that was initiated within 72 h after stroke onset. For both studies, the
original analysis data were used for meta-analysis (individual patient data
analysis). The combination of these two studies by meta-analytic procedures was
pre-planned, and the methods were pre-defined under blinded conditions. The
nonparametric Mann-Whitney (MW) effect size of the two studies on the ARAT score
on day 90 indicated superiority of Cerebrolysin compared with placebo (MW 0.62, P
< 0.0001, Wei-Lachin pooling procedure, day 90, last observation carried forward;
N = 442). Also, analysis of early benefit at day 14 and day 21 by means of the
National Institutes of Health Stroke Scale, which is regarded as most sensitive
to early improvements, showed statistical significance (MW 0.59, P < 0.002). The
corresponding number-needed-to-treat (NNT) for clinically relevant changes in
early NIHSS was 7.1 (95% CI: 4 to 22). Cerebrolysin had a beneficial effect on
motor function and neurological status in early rehabilitation patients after
acute ischemic stroke. Safety aspects were comparable to placebo, showing a
favourable benefit/risk ratio.
PMID- 28707131
TI - Posterior locked lateral compression injury of the pelvis in geriatric patients:
an infrequent and specific variant of the fragility fracture of pelvis.
AB - INTRODUCTION: Posterior locked lateral compression injury (PLLCI) of the pelvic
ring is an infrequent variant of lateral compression injury, a condition
described in only eight reported cases since 2000. Lateral compression injury
usually results from high-energy trauma and is characterized by locking between
the medially translated fractured ilium and the anterior border of the sacrum,
regardless of whether the fractured ilium involves the sacroiliac joint. However,
in our experience, lateral compression injury can also result from low-energy
trauma as a manifestation of pelvic fragility fracture. The aim of the present
study was to describe this rare form of PLLCI in a case series of geriatric
patients. METHODOLOGY: A retrospective analysis of consecutive patients with
pelvic ring injuries who were admitted to our hospital from January 2008 to April
2015 identified seven geriatric patients (1 male and 6 females; median age 81
years) with a form of PLLCI. RESULTS: All injuries were due to falls from a
standing position onto the ground. All seven cases demonstrated characteristics
of a locking fractured ilium over the anterior border of the sacrum on axial
computed tomography images, but were not detected on plain radiographs. All
underwent follow-up at 1 year or later with improved mean visual analogue scale
scores (range 0-3). Regarding Koval walking ability scores, patients who
underwent pelvic brim plating with anterior external fixation were more likely to
regain their pre-injury walking ability than patients who only underwent anterior
external fixation or conservative treatment. CONCLUSION: Geriatric patients can
experience PLCCIs of the pelvis due to low-energy trauma. These fractures have
different characteristics from those associated with severe injuries due to high
energy trauma, and they comprise an infrequent form of Rommens fragility fracture
of the pelvis (type IIIa). In these cases, appropriate surgical management that
includes sacroiliac plating combined with anterior external fixation can yield
good outcomes.
PMID- 28707132
TI - Comparison of lateral and skyline fluoroscopic views for detection of prominent
screws in distal radius fractures plating: results of an ultrasonographic study.
AB - INTRODUCTION: Extensor tendon rupture is a recognized complication of volar plate
fixation of distal radius fractures due to screws protruding past the dorsal
cortex. The aim of this study was to compare the Skyline view with traditional
lateral fluoroscopic views using ultrasonography as a reference standard in the
postoperative assessment. MATERIALS AND METHODS: A monocentric prospective study
was conducted to identify screws penetrating the dorsal cortex after volar
plating of distal radius fractures. PATIENTS AND INTERVENTION: Intraoperative
anteroposterior (AP) and lateral views were used for group A (28 patients). AP,
lateral and skyline fluoroscopic views were used for Group B (40 patients).
Prominent screws were changed. MAIN OUTCOME MEASUREMENTS: Ultrasound was done 6
months postoperatively to evaluate the number and length of prominent dorsal
screws and any signs of extensor tenosynovitis. RESULTS: The number of prominent
dorsal screws exceeding 1 mm was 14 in group A (14.9%), and 16 screws (11.8%) in
group B (p = 0.487). Average length of prominent dorsal screw was 1.9 mm (range 1
2.1 mm) for group A and 2.4 mm (range 1.1-4.8 mm) for group B (p = 0.534). The
number of patients with extensor tenosynovitis was 11 for group A and 12 for
group B (p = 0.66). CONCLUSIONS: The Skyline view does not provide sensitive and
reliable detection of the dorsal screw penetration. Intraoperative ultrasound
might be a better tool to detect screw prominence. LEVEL OF EVIDENCE: III, case
control study.
PMID- 28707133
TI - Changes of spinopelvic parameters in different positions.
AB - INTRODUCTION: To observe changes of spinopelvic parameters and the presence of
pelvic incidence (PI) variation in different positions, and the accuracy of PI
compared with CT scan. MATERIALS AND METHODS: Patients with standing whole-spine
radiograph, CT scan of the pelvic bone, and MRI of the lumbar spine done within a
few days were included. The pelvic [pelvic tilt (PT), sacral slope (SS), and PI]
and spinal [lumbar lordosis (LL)] parameters were measured by two different
observers. RESULTS: The PIs from radiograph were significantly greater than those
from CT in both observers. By adopting the upper limit of the confidence interval
and the agreement of two observers on grouping, patients were categorized into
two subgroups (SG1, with less PI change; SG2, with higher PI change). The PT and
LL values decreased, whereas SS increased significantly from standing to supine
positions in SG1. Significantly decreased PT and PI from standing to supine were
observed in SG2. All pelvic parameters and the sagittal vertical axis on
radiograph, and the LL amount on MRI were significantly greater in SG2 than in
SG1. CONCLUSIONS: Majority of patients demonstrated alignment changes of
unchanged PI with decreased PT and LL, and increased SS from standing to supine;
however, decreased PT and PI and fixed SS and LL were also demonstrated. Patients
with higher PI change have high values in three pelvic parameters and sagittal
vertical axis, and fixed LL.
PMID- 28707134
TI - [Synthetic bone replacement : Current developments and perspectives].
AB - Successful reconstruction of critical bone defects requires complete elimination
of the underlying pathology, preservation or restoration of mechanical stability
of the affected bone segment and, most importantly, an adequate filling material
that supports the regeneration and formation of new bone within the treated
defect in an optimal fashion. Currently available synthetic bone graft
substitutes cannot address all requirements of such a complex biological process
individually. Due their suboptimal and, with respect to physiological bone
healing, asynchronous biodegradation properties, their specific foreign material
mediated side effects and complications and fairly modest overall osteogenic
potential, their overall clinical performance typically lags behind conventional
bone grafts. However, a defect and pathology specific combination of synthetic
bone graft substitutes with appropriate carrier properties, therapeutic agents
and/or conventional bone graft materials allows the creation of biologically
enhanced composite constructs that can surpass the biological and therapeutic
limits of autologous bone grafts. This monograph presents a new concept based on
the biological enhancement of optimal therapeutic agent-carrier composites and
provides a rationale for an individual, requirement-specific adaptation of a
truly patient-specific bone defect reconstruction.
PMID- 28707135
TI - Secondary Stroke Prevention in Cryptogenic Stroke and Embolic Stroke of
Undetermined Source (ESUS).
AB - PURPOSE OF THE REVIEW: The purpose of the study was to review the literature on
cryptogenic stroke and embolic stroke of undetermined stroke (ESUS). Cryptogenic
stroke according to TOAST criteria is a stroke which is not due to cardiogenic
embolism, small vessel disease with lacunes or large vessel disease of brain
supplying arteries. In the context of secondary stroke prevention studies,
cryptogenic stroke is not operationally defined. RECENT FINDINGS: The new concept
of "embolic stroke of undetermined source" (ESUS) provides an operational
definition. ESUS is diagnosed as a non-lacunar stroke on cerebral imaging and
exclusion of large vessel atherosclerosis by CTA, MRA or ultrasound. Cardiogenic
embolism is made less likely by ECG monitoring and echocardiography. At present,
aspirin is used for secondary stroke prevention in patients with cryptogenic
stroke. Based on the construct that ESUS might be caused by undetected atrial
fibrillation or other embolic mechanisms, ongoing randomised secondary stroke
prevention trials are comparing non-vitamin K oral anticoagulants (NOACs) with
aspirin.
PMID- 28707136
TI - The formation of a functional retinal pigment epithelium occurs on porous
polytetrafluoroethylene substrates independently of the surface chemistry.
AB - Subretinal transplantation of functioning retinal pigment epithelial (RPE) cells
may have the potential to preserve or restore vision in patients affected by
blinding diseases such as age-related macular degeneration (AMD). One of the
critical steps in achieving this is the ability to grow a functioning retinal
pigment epithelium, which may need a substrate on which to grow and to aid
transplantation. Tailoring the physical and chemical properties of the substrate
should help the engineered tissue to function in the long term. The purpose of
the study was to determine whether a functioning monolayer of RPE cells could be
produced on expanded polytetrafluoroethylene substrates modified by either an
ammonia plasma treatment or an n-Heptylamine coating, and whether the difference
in surface chemistries altered the extracellular matrix the cells produced.
Primary human RPE cells were able to form a functional, cobblestone monolayer on
both substrates, but the formation of an extracellular matrix to exhibit a
network structure took months, whereas on non-porous substrates with the same
surface chemistry, a similar appearance was observed after a few weeks. This
study suggests that the surface chemistry of these materials may not be the most
critical factor in the development of growth of a functional monolayer of RPE
cells as long as the cells can attach and proliferate on the surface. This has
important implications in the design of strategies to optimise the clinical
outcomes of subretinal transplant procedures.
PMID- 28707137
TI - Surface modification of esophageal stent materials by a polyethylenimine layer
aiming at anti-cancer function.
AB - Esophageal cancer is difficult to cure globally and possesses high mortality
rate, and it is generally accepted that palliative care such as stent
implantation is the main therapy method for esophageal cancer in later period.
However, the restenosis caused by tumor cells and inflammatory cells seriously
interferes the stent clinical application and limits its long-term services. To
solve this problem, series of drug delivery stents were developed and proven
rather effective in the early stage of implantation, but more serious restenosis
occurred after the drug delivery was over, which endangered the patients' life.
Therefore, endowing the esophageal stent continuous anti-cancer function become
an ideal strategy for inhibiting the restenosis. In this contribution, the
functional layer composed of polydopamine (PDA) and Poly-ethylenimine (PEI) with
series of molecular weights (MW, 1.8 * 103, 1 * 104, 2.5 * 104 and 7 * 104 Da)
were fabricated onto the esophageal stent material 317L stainless steel (317L SS)
surface. The surface characterization including amine quantitative, atomic force
microscopy (AFM) and water contact angle measurement indicated successful
preparation of the PDA/PEI layer. The Eca109 cells culture results proved that
the PDA/PEI layers significantly improve Eca109 cells apoptosis and necrosis,
suggesting excellent anti-cancer function. In addition, we also found that the
anti-cancer function of the PDA/PEI layers was positively correlated to the
immobilized PEIs' MW. All the results demonstrated the potential application of
the PDA/PEI layers on the surface modification of esophageal stent for continuous
anti-cancer function. It is generally accepted that the restenosis caused by
tumor cells seriously interferes the esophageal stent clinical application. Thus,
endowing the esophageal stent continuous anti-cancer function is the ideal
strategy for inhibiting the restenosis. In this work, we fabricated functional
layers composed of polydopamine (PDA) and Poly-ethylenimine (PEI) with series of
molecular weights (MW, 1.8 * 103, 1 * 104, 2.5 * 104 and 7 * 104 Da) onto the
esophageal stent material 317L stainless steel (317L SS) surface to inhibit the
tumor cells growth, and this function was related to the PEIs' molecular weights.
The functional PDA/PEI layers were expected potentially applied for surface
modification of esophageal stent materials.
PMID- 28707138
TI - Gray matter changes and cognitive predictors of 2-year follow-up abnormalities in
early-onset first-episode psychosis.
AB - This study aims to examine regional gray matter (GM) changes over a period of 2
years in patients diagnosed with early-onset first-episode psychosis (EO-FEP),
and to identify baseline predictors of abnormalities at the follow-up. Fifty-nine
patients with EO-FEP aged 11-17 years were assessed. Magnetic resonance imaging
was carried out at admission and 2 years later. Changes over time were assessed
with voxel-based morphometry. Fifty-nine patients (34 schizophrenia-SCZ, 15
bipolar disorder-BP, and 10 other psychotic disorders) and 70 healthy controls
were assessed. At baseline no differences were found between the EO-FEP groups
and control subjects. Over time, SCZ patients presented a larger GM decrease in
the orbitofrontal cortex, anterior midline frontal cortex, cingulate, left
caudate, and thalamus. BP patients also had a larger GM decrease in the right
putamen, right orbitofrontal cortex, and anterior and midline region of the right
superior frontal gyrus and left caudate, but with fewer areas showing significant
differences than in the comparison between SCZ and controls. In the cross
sectional analysis, only SCZ patients showed differences with respect to controls
in some GM areas. Significant baseline predictors of a 2-year reduction in GM
were IQ and working memory. EO-FEP patients did not show differences in GM
compared to controls at baseline. Both SCZ and BP patients showed a greater
decrease in specific areas during the first 2 years. At follow-up, only SCZ
patients differed significantly from controls in specific brain areas. The GM
reduction was predicted by baseline cognitive variables.
PMID- 28707139
TI - Patients' Knowledge of Prenatal Screening for Trisomy 21.
AB - This study's objective was to assess the knowledge of prenatal screening for
Trisomy 21 in pregnant women in one institution in Canada. A cross-sectional
survey measuring demographics, knowledge of screening, and health literacy, was
administered to pregnant women. Of the 135 women who completed the survey, 74%
had adequate knowledge of Trisomy 21 and associated screening procedures. Twenty
eight point one percent of women did not receive any counseling. Overall, 29.5%
of women did not know that the screening test was optional and 10.2% of women
underwent screening prior to having been counseled. Multigravidity (p < 0.05) and
prior counseling (p < 0.001) were positively correlated with knowledge while
first language other than English (p < 0.001) was negatively correlated with
knowledge. Given these findings, an effort needs to be made on the part of health
care providers to increase counseling rates to 100%, stressing the optional
nature of the test to attain true informed consent.
PMID- 28707140
TI - Disordered Gambling Prevalence: Methodological Innovations in a General Danish
Population Survey.
AB - We study Danish adult gambling behavior with an emphasis on discovering patterns
relevant to public health forecasting and economic welfare assessment of policy.
Methodological innovations include measurement of formative in addition to
reflective constructs, estimation of prospective risk for developing gambling
disorder rather than risk of being falsely negatively diagnosed, analysis with
attention to sample weights and correction for sample selection bias, estimation
of the impact of trigger questions on prevalence estimates and sample
characteristics, and distinguishing between total and marginal effects of risk
indicating factors. The most significant novelty in our design is that nobody was
excluded on the basis of their response to a 'trigger' or 'gateway' question
about previous gambling history. Our sample consists of 8405 adult Danes. We
administered the Focal Adult Gambling Screen to all subjects and estimate
prospective risk for disordered gambling. We find that 87.6% of the population is
indicated for no detectable risk, 5.4% is indicated for early risk, 1.7% is
indicated for intermediate risk, 2.6% is indicated for advanced risk, and 2.6% is
indicated for disordered gambling. Correcting for sample weights and controlling
for sample selection has a significant effect on prevalence rates. Although these
estimates of the 'at risk' fraction of the population are significantly higher
than conventionally reported, we infer a significant decrease in overall
prevalence rates of detectable risk with these corrections, since gambling
behavior is positively correlated with the decision to participate in gambling
surveys. We also find that imposing a threshold gambling history leads to
underestimation of the prevalence of gambling problems.
PMID- 28707141
TI - Do 'literate' pigeons (Columba livia) show mirror-word generalization?
AB - Many children pass through a mirror stage in reading, where they write individual
letters or digits in mirror and find it difficult to correctly utilize letters
that are mirror images of one another (e.g., b and d). This phenomenon is thought
to reflect the fact that the brain does not naturally discriminate left from
right. Indeed, it has been argued that reading acquisition involves the
inhibition of this default process. In the current study, we tested the ability
of literate pigeons, which had learned to discriminate between 30 and 62 words
from 7832 nonwords, to discriminate between words and their mirror counterparts.
Subjects were sensitive to the left-right orientation of the individual letters,
but not the order of letters within a word. This finding may reflect the fact
that, in the absence of human-unique top-down processes, the inhibition of mirror
generalization may be limited.
PMID- 28707142
TI - Myosin II sequences for Lethocerus indicus.
AB - We present the genomic and expressed myosin II sequences from the giant waterbug,
Lethocerus indicus. The intron rich gene appears relatively ancient and contains
six regions of mutually exclusive exons that are alternatively spliced.
Alternatively spliced regions may be involved in the asymmetric myosin dimer
structure known as the interacting heads motif, as well as stabilizing the
interacting heads motif within the thick filament. A lack of negative charge in
the myosin S2 domain may explain why Lethocerus thick filaments display a
perpendicular interacting heads motif, rather than one folded back to contact S2,
as is seen in other thick filament types such as those from tarantula.
PMID- 28707143
TI - Clinical Sleep-Wake Disorders II: Focus on Insomnia and Circadian Rhythm Sleep
Disorders.
AB - Insomnia and circadian rhythm sleep disorders affect large proportions of the
population and have pronounced effects on quality of life and daytime
performance. While the neurobiology of insomnia is not yet fully understood,
circadian rhythm sleep disorders are assumed to be caused by a mismatch between
the individual circadian phase position and the desired sleep-wake schedule.
Benzodiazepines and non-benzodiazepine positive allosteric GABAA receptor
modulators improve sleep onset and maintenance in the short-term treatment of
insomnia. However, tolerance and dependence are important side effects. Sedating
antidepressants are frequently prescribed for insomnia, however, only few
randomised controlled trials have been published so far. Melatonin and melatonin
receptor agonists are considered to be an option for the treatment of insomnia
especially because of their minimal abuse potential and safety. First data on
orexin (aka hypocretin) receptor antagonists are promising, however, the risk
benefit ratio needs to be further evaluated. With respect to circadian rhythm
sleep disorders, there is solid evidence from meta-analyses supporting the use of
melatonin in jet lag disorder to accelerate entrainment to the new time zone, and
in delayed sleep phase disorder to advance sleep-wake rhythms. In addition to
that, there is evidence supporting the use of melatonin in patients with shift
work disorder in order to promote daytime sleep after night shifts.
PMID- 28707144
TI - Efficacy and safety of argon plasma coagulation in the management of extensive
chronic radiation proctitis after pelvic radiotherapy for cervical carcinoma.
AB - INTRODUCTION: Chronic radiation proctitis (CRP) usually develops 90 days or more
after radiation. Currently, there is no standard available for the treatment of
CRP. In argon plasma coagulation, monopolar diathermy is used to ionise the argon
gas which coagulates the telengiectatic vessels in a noncontact fashion. However,
there are very few studies which have reported its use in extensive CRP. We
report the efficacy and safety of APC in seven patients with recurrent, extensive
grade 3 radiation proctitis. MATERIALS AND METHODS: This is a retrospective
analysis of patients treated with argon plasma coagulation in our institute from
June 2013 to June 2016. After adequate bowel preparation, patients underwent APC
at an average power of 50 W with flow rate of 5 L/min. All the visible
telangiectasia was ablated which required many sittings. RESULTS: The median
RPSAS symptom score for frequency of bleeding at enrolment was 5 (range 3-5).
After completion of APC, the median RPSAS symptom score for frequency of bleeding
decreased to 1. The median RPSAS symptom score for severity of bleeding was 5
(range 3-5). After completion of APC, the mean RPSAS symptom score for severity
of bleeding decreased to 1. Mean haemoglobin level before treatment was 5.43 g/dl
(SD 2.37). Mean haemoglobin level after treatment was10.04 g/dl (SD 2.0).
Compared with pre-treatment levels after APC, there was a mean increase in
haemoglobin of 4.61 + 1.78 [95% CI 2.97-6.25, p = 0.00]. CONCLUSION: Argon plasma
coagulation is a safe, well tolerated and effective treatment option in extensive
chronic radiation proctitis which is refractory to medical management.
PMID- 28707145
TI - Numerical Relationships Between Archaeal and Bacterial amoA Genes Vary by
Icelandic Andosol Classes.
AB - Bacterial amoA genes had not been detectable by qPCR in freshly sampled Icelandic
Andosols thus far. Hence, a new primer set yielding shorter gene fragments has
been designed to verify the absence of ammonia-oxidizing bacteria in different
Icelandic Andosol classes. At the same time, a new primer set was also
constructed for archaeal amoA genes that should improve the quality of PCR
products. Although a large part of the soil samples were found to be amoA
negative, bacterial amoA genes were detectable with new as well as old primer
sets. The same results were obtained for the archaeal amoA genes. The relative
distribution of archaeal and bacterial amoA genes varied between Andosol classes.
Archaeal amoA genes were significantly more abundant in Brown than in Histic
Andosols, while the opposite was observed for bacterial amoA genes. The numbers
of archaeal and bacterial amoA genes in Gleyic Andosols were not significantly
different from those in Histic and Brown Andosols. The numbers of bacterial amoA
genes, but not the numbers of archaeal amoA genes, correlated significantly and
positively with potential ammonia oxidation activities. The presence of the
bacterial nitrification inhibitor allylthiourea inhibited the potential ammonia
oxidation activities during the first 12 h of incubation. Hence, it was concluded
that ammonia-oxidizing bacteria profited most from the conditions during the
measurements of potential ammonia oxidation activities.
PMID- 28707146
TI - Association between G1733A (rs6152) polymorphism in androgen receptor gene and
recurrent spontaneous abortions in Mexican population.
AB - INTRODUCTION: Recurrent spontaneous abortion (RSA) is a multifactorial condition
that occurs with a frequency of 0.2-5% in women of reproductive age. Among
genetic factors, the single nucleotide polymorphism (SNP) G1733A in the androgen
receptor (AR) gene has been associated with its presence in Greek and Iranian
populations. Therefore, the aim of this study is to determine its possible
association with RSA in this population. PATIENTS AND METHODS: A total of 156
Mexican RSA (with at least 2 consecutive abortions) unrelated patients and 152
unrelated healthy women were included, the presence of karyotype anomalies in the
parents as well as uterine anomalies as well as antiphospholipid antibodies was
excluded in patients; while all the controls presented at least two healthy
pregnancies and no abortion. In all the included women, the presence of the SNP
G1733A was determined by restriction fragment length polymorphism (RFLP)
technique. RESULTS: No significant differences were observed in age between
groups. The genotype GG, GA, and AA had a frequency of 0.70, 0.27, and 0.03 in
controls and of 0.89, 0.10, and 0.01 in patients (p < 0.001); while the A allele
frequency was of 0.06 and 0.16 in controls and patients, respectively (p <
0.0001). The difference in allele frequency increased 10-15% when patients with
primary RSA (with no live births) and with at least three abortions were
included. CONCLUSIONS: The SNP G1733A of the AR gene is significantly associated
with RSA in Mexican patients. These results coincide with previous reports in
other populations.
PMID- 28707147
TI - The HLA-G 14-bp polymorphism and recurrent implantation failure: a meta-analysis.
AB - PURPOSE: The human leucocyte antigen-G (HLA-G) 14-bp insertion/deletion
polymorphism was implicated in recurrent implantation failure (RIF), but
individual published studies showed inconclusive results. Thus, a meta-analysis
was performed to clarify the effect of HLA-G 14-bp polymorphism on RIF risk.
METHODS: A comprehensive search for relevant articles was conducted. The odds
ratios (ORs) and 95% confidence intervals (CIs) for HLA-G 14-bp polymorphism and
RIF were calculated. RESULTS: A total of five studies were included. In studies
conducted in RIF patients and controls who had at least one spontaneous
pregnancy, meta-analysis revealed no statistically significant association
between the HLA-G 14-bp polymorphism and RIF in allele contrast and all genetic
models in the overall population, but significant association was found in the
population of Caucasian origin under allele contrast (OR = 1.73, 95% CI, 1.20,
2.50) and genetic models of +14 bp/+14 bp vs. -14 bp/-14 bp (OR = 3.09, 95% CI,
1.43, 6.65). In studies conducted in RIF patients and controls who had successful
pregnancy following IVF-ET, the meta-analysis showed that there was statistically
significant association between the HLA-G 14 bp polymorphism and RIF in allele
contrast (OR = 1.74, 95% CI, 1.13, 2.67) and genetic models of +14 bp/+14 bp vs.
14 bp/-14 bp (OR = 10.20, 95% CI, 2.47, 42.14) and dominant model (OR = 4.34, 95%
CI, 1.72, 10.92). No publication bias was found in the present studies.
CONCLUSIONS: This meta-analysis suggested that the HLA-G 14-bp insertion allele
may increase the risk of RIF in Caucasians. Further studies with large sample
size of different ethnic populations are necessary.
PMID- 28707148
TI - Chemokine (C-C motif) ligand-2 (CCL2) and oxidative stress markers in recurrent
pregnancy loss and repeated implantation failure.
AB - PURPOSE: The main purpose of this study is to evaluate the inflammatory response
and oxidative stress together in the cases of recurrent pregnancy loss (RPL) and
repeated implantation failure (RIF). METHODS: This is a cross-sectional study
conducted to compare infertile patients who have RIF and patients with RPL
histories in terms of CCL2, TAS, TOS, and OSI. To this end, two study groups were
formed by primary-infertile women with RIF history and women with nulliparous RPL
history who consulted a university hospital between 2014 and 2016, and a control
group was formed by multiparous women who had no pregnancy loss. With 30 women in
each group, 90 women in total were included in the study. CCL2, TAS, and TOS
blood levels were measured and oxidative stress index was calculated in all
participants. RESULTS: The patients with RPL and RIF had higher levels of CCL2
than those in the control group. The TOS, TAS, and OSI levels did not differ in
RPL and RIF groups from the control group. No statistically significant
relationship was found between CCL2 and the TOS, TAS, and OSI values.
CONCLUSIONS: Oxidative stress markers in the pregestational period did not have a
predictive value in the RPL and RIF. CCL2 might be useful in risk prediction.
PMID- 28707149
TI - Long-term quality of life and outcomes following robotic assisted TAPP inguinal
hernia repair.
AB - Laparoscopic TAPP inguinal hernia repair is an established alternative to open
hernia repair, which offers equivalent outcomes with less postoperative pain and
faster recovery. Unfortunately, it remains technically challenging, requiring
advanced laparoscopic skills which have limited its popularity among surgeons.
The robotic platform has the potential to overcome these challenges. The
objective of this study was to examine the long-term quality of life and outcomes
following robotic assisted TAPP inguinal hernia repair, since these data have not
been reported up to now. From October 2012 to October 2015, 159 inguinal hernias
in 82 consecutive patients were repaired with 3D mesh (BARD) using da Vinci Si
Surgical System (Intuitive Surgical, Sunnyvale, CA, USA). The patients'
demographics and intraoperative data were documented. Patients were seen 2 and 6
weeks after the surgery and the complications were recorded. Patients were
assessed 6 weeks after the surgery by a survey using a universal pain assessment
tool to document their post-operative pain, narcotic use and time of return to
work and exercise. A modified short form 12 (SF 12) was also sent out to the
patients 12-36 months after the surgery to measure their health-related quality
of life prior to surgery and at the 12- to 36-month follow-up, and to document
any evidence of recurrence. Postoperative health-related quality of life scores
were compared to the pre-operative baseline quality of life scores using the
unpaired t test. Over the course of 3 years, 159 robotic assisted TAPP inguinal
hernia repair were performed in 82 patients, 73 men and 9 women by one surgeon as
an outpatient basis. The mean age was 53 and mean body mass index was 26. There
were no intraoperative complications or conversions. The average operative time
was 99 min. Four patients developed urinary retention post-operatively and one
patient developed postoperative bowel obstruction requiring laparoscopic lysis of
adhesion with no long-term complications. All patients completed the pain
assessment survey and the median pain score, 3 days after the surgery was 3.
Narcotics were used for an average of 3.1 days. The modified SF 12 survey
assessing for quality of life before and 12-36 months after surgery was completed
and returned by 29 patients (response rate of 35.4% and median follow-up of 32
months). Only one recurrence was reported which was repaired with open technique.
The analysis of the SF 12 survey that evaluated patient's quality of life, pain
score and the ability to perform activities of daily living before and after
surgery revealed a significant improvement in those measures 12-36 months after
the surgery compare to their baseline. Hernia recurrence, chronic pain and
physical impairment are the major long-term concerns after any type of inguinal
hernia repair. Our results demonstrate that robotic assisted TAPP inguinal hernia
repair appears to be a technically feasible, reproducible and safe minimally
invasive alternative with low recurrence, low chronic pain and high health
related quality of life in the long term.
PMID- 28707150
TI - [Cardiac Magnetic Resonance Imaging : The significance of the calculated
extracellular volume as a marker of diffuse myocardial fibrosis].
PMID- 28707151
TI - [Acceptance of medical apps and e-books among German radiologists].
AB - PURPOSE: Smartphones, tablet PCs, mobile applications (apps) and electronic book
files (e-books) affect our lives in private and job-related settings. The aim of
this study was to analyze the behavior of radiologists on smartphones, tablet PCs
and e-books and to investigate its effect on their daily work. MATERIALS AND
METHODS: An online survey containing of 23 questions was conducted using Survey
Monkey(c) ( www.surveymonkey.com ). The invitation to the survey was done using
the newsletter of the German Radiological Society (DRG). The acquired data was
automatically stored by the software and then analyzed using descriptive
statistics. RESULTS: In total, 104 radiologists (29% female) participated in the
online survey. Of these, 93% and 96.5% owned a smartphone or a tablet PC,
respectively, and 72% and 67% used medical apps and e-books, respectively.
Through their use, 31% found moderate and 41% found enormous improvement in their
daily work. A majority of participating radiologists would be willing to pay an
increased user fee for optimized apps or e-books. CONCLUSION: With currently only
moderate individual benefit of mobile medical apps and e-books, there is a
widespread need for optimally configured apps and e-books with a correspondingly
high market potential. KEY POINTS: (1) Radiologists use smartphones (93%) or
tablet PCs (96.5%); (2) 72% of radiologists use a smartphone or tablet PC for
medical material; (3) 53% of radiologists report significant assistance from or a
high value of the mobile medical applications used; (4) There is a willingness to
pay a license fee for optimized mobile applications or e-books.
PMID- 28707152
TI - [177Lu-PSMA radioligand therapy for advanced prostate cancer].
PMID- 28707153
TI - Medium-Chain Enriched Diacylglycerol (MCE-DAG) Oil Decreases Body Fat Mass in
Mice by Increasing Lipolysis and Thermogenesis in Adipose Tissue.
AB - Medium chain fatty acid (MCFA) escapes the formation of chylomicrons in the small
intestine, resulting in energy expenditure through beta-oxidation. Diacylglycerol
(DAG) is susceptible to oxidation rather than being stored in the adipose tissue.
This study was conducted to verify the effect of MCE-DAG oil on body fat mass in
vivo. Male C57BL/6 mice were randomly assigned to four groups (n = 12) as
follows: (1) normal diet (18% kcal from fat), (2) canola oil as a control (40%
kcal from canola oil), (3) MCE-DAG10 (10% kcal from MCE-DAG + 30% kcal from
canola oil), and (4) MCE-DAG20 (20% kcal from MCE-DAG + 20% kcal from canola
oil). The body weight and fat mass of MCE-DAG20 group mice were decreased
relative to those of control mice (P < 0.05 and P < 0.001, respectively). Serum
triacylglycerol (TAG) was decreased in both MCE-DAG10 and MCE-DAG20 groups (P <
0.01 and P < 0.05, respectively). Hormone sensitive lipase (HSL) and adipose
triglyceride lipase (ATGL) were increased in the MCE-DAG20 group relative to the
control in white adipose tissue (WAT) (P < 0.05). Uncoupling protein 1 (UCP1) was
also increased in the MCE-DAG20 group relative to the control in brown adipose
tissue (BAT) (P < 0.05). In summary, MCE-DAG reduced body fat mass likely by
stimulating lipolysis in WAT and thermogenesis in BAT.
PMID- 28707154
TI - Personality and the Intergenerational Transmission of Educational Attainment:
Evidence from Germany.
AB - Research based in the United States, with its relatively open educational system,
has found that personality mediates the relationship between parents' and child's
educational attainment and this mediational pattern is especially beneficial to
students from less-educated households. Yet in highly structured, competitive
educational systems, personality characteristics may not predict attainment or
may be more or less consequential at different points in the educational career.
We examine the salience of personality in the educational attainment process in
the German educational system. Data come from a longitudinal sample of 682 17 to
25 year-olds (54% female) from the 2005 and 2015 German Socio-Economic Panel
(SOEP). Results show that adolescent personality traits-openness, neuroticism,
and conscientiousness-are associated with educational attainment, but personality
plays a negligible role in the intergenerational transmission of education.
Personality is influential before the decision about the type of secondary degree
that a student will pursue (during adolescence). After that turning point, when
students have entered different pathways through the system, personality is less
salient. Cross-national comparisons in a life course framework broaden the scope
of current research on non-cognitive skills and processes of socioeconomic
attainment, alerting the analyst to the importance of both institutional
structures and the changing importance of these skills at different points in the
life course.
PMID- 28707155
TI - And What About Siblings? A Longitudinal Analysis of Sibling Effects on Youth's
Intergroup Attitudes.
AB - Within the process of political socialization, the family is of particular
importance. Apart from parents, however, little is known about the role of other
close family members. The present study examined if siblings affect each other's
intergroup attitudes (i.e., intolerance towards immigrants, social dominance
orientation). Drawing on a sample of 362 sibling dyads (older siblings: M age =
17.77, 53.6% female; younger siblings: M age = 13.61, 61.3% female), the results
showed that older siblings' intergroup attitudes predicted younger siblings'
attitudes, but this effect was moderated by gender. Specifically, older siblings'
intolerance and social dominance orientation were only found to affect their
younger sisters, yet not their younger brothers. Although younger siblings'
intergroup attitudes had no main effect on older siblings, a significant
moderation by age indicated that younger siblings affected older siblings' social
dominance orientation with increasing age. These moderation effects of age and
gender were not mediated by the quality of family relationships. The findings
also remained the same when parental intergroup attitudes were taken into
account. While siblings were generally identified as an important agent of
political socialization in youth, the results also highlight the necessity to
further examine the mechanism that either facilitate or hinder sibling effects.
PMID- 28707156
TI - Trajectories of mood and stress and relationships with protective factors during
the transition to menopause: results using latent class growth modeling in a
Canadian cohort.
AB - The menopause transition is characterized by significant hormonal changes that
may predispose women to psychosocial maladjustment. Prospective studies to date
have focused primarily on negative mood states and show equivocal findings. The
primary goal of this study was to identify patterns of change with respect to
positive and negative mood states (vigor, depression, tension, and stress) over a
5-year period in a cohort of women undergoing the transition to menopause. A
secondary aim was to determine whether the identified trajectories were
associated with menopause status as well as baseline health-related and
psychological characteristics. This longitudinal study observed 102 healthy
Canadian women who were premenopausal at baseline (age 47-55 years). Analyses
consisted of latent class growth modeling. Mood states were predominantly normal
and stable, raising doubts regarding the notion that psychosocial distress is a
common and natural occurrence during the transition to menopause. Neither time
spent in perimenopause nor BMI had a significant influence on levels of mood
indicators. However, higher scores on body image, self-esteem, and general health
perceptions were predictive of more positive psychological outcomes over the 5
year period. Targeting improvements in self-perceptions may promote a healthier
psychological adjustment during this natural transitional period in a women's
lifespan.
PMID- 28707157
TI - Parcellation of Macaque Cortex with Anatomical Connectivity Profiles.
AB - The macaque model has been widely used to investigate the brain mechanisms of
specific cognitive functions and psychiatric disorders. However, a detailed
functional architecture map of the macaque cortex in vivo is still lacking. Here,
we aimed to construct a new macaque cortex atlas based on its anatomical
connectivity profiles using in vivo diffusion MRI. First, we defined the macaque
cortical seed areas using the NeuroMaps atlas. Then, we applied the anatomical
connectivity patterns-based parcellation approach to parcellate the macaque
cortex into 80 subareas in each hemisphere, which were approximately symmetric
between the two hemispheres. In each hemisphere, we identified 14 subareas in the
frontal cortex, 9 subareas in the somatosensory cortex, 13 subareas in the
parietal cortex, 16 subareas in the temporal cortex, 16 subareas in the occipital
cortex, and 12 subareas in the limbic system. Finally, the graph-based network
analyses of the anatomical network based on newly constructed macaque cortex
atlas identified seven hub areas including bilateral ventral premotor cortex,
bilateral superior parietal lobule, right medial precentral gyrus, and right
precuneus. This newly constructed macaque cortex atlas may facilitate studies of
the structure and functions of the macaque brain in the future.
PMID- 28707158
TI - 3D quantitative analysis of early decomposition changes of the human face.
AB - Decomposition of the human body and human face is influenced, among other things,
by environmental conditions. The early decomposition changes that modify the
appearance of the face may hamper the recognition and identification of the
deceased. Quantitative assessment of those changes may provide important
information for forensic identification. This report presents a pilot 3D
quantitative approach of tracking early decomposition changes of a single cadaver
in controlled environmental conditions by summarizing the change with weekly
morphological descriptions. The root mean square (RMS) value was used to evaluate
the changes of the face after death. The results showed a high correlation (r =
0.863) between the measured RMS and the time since death. RMS values of each scan
are presented, as well as the average weekly RMS values. The quantification of
decomposition changes could improve the accuracy of antemortem facial
approximation and potentially could allow the direct comparisons of antemortem
and postmortem 3D scans.
PMID- 28707159
TI - Introduction to the Special Issue of JCP-A featuring the Presidential Symposium
at the International Congress of Neuroethology, ICN 2016 in Montevideo.
PMID- 28707160
TI - Systems for deep brain stimulation: review of technical features.
AB - The use of deep brain stimulation (DBS) is an important treatment option for
movement disorders and other medical conditions. Today, three major manufacturers
provide implantable systems for DBS. Although the underlying principle is
basically the same for all available systems, the differences in the technical
features vary considerably. This article outlines aspects regarding the technical
features of DBS systems. The differences between voltage and current sources are
addressed and their effect on stimulation is shown. To maintain clinical benefit
and minimize side effects the stimulation field has to be adapted to the
requirements of the patient. Shaping of the stimulation field can be achieved by
the electrode design and polarity configuration. Furthermore, the electric signal
consisting of stimulation rate, stimulation amplitude and pulse width affect the
stimulation field. Interleaving stimulation is an additional concept, which
permits improved treatment outcomes. Therefore, the electrode design, the
polarity, the electric signal, and the concept of interleaving stimulation are
presented. The investigated systems can be also categorized as rechargeable and
non-rechargeable, which is briefly discussed. Options for interconnecting
different system components from various manufacturers are presented. The present
paper summarizes the technical features and their combination possibilities,
which can have a major impact on the therapeutic effect.
PMID- 28707161
TI - A weight-independent association between atypical antipsychotic medications and
obstructive sleep apnea.
AB - BACKGROUND: With increasing use of atypical antipsychotic (AAP) agents, the
concern has been raised about the association between AAP agents and medical
complications. Obstructive sleep apnea (OSA) is a common breathing disorder that
adversely affects health and quality of life. Because the major risk factors for
OSA are weight gain and obesity by altering the upper airway anatomy, an
association between AAP and development of OSA is predictable. However, we
hypothesized that AAP may promote OSA not only by weight gain but also because of
its potential effects on upper airway muscle function. In the present study, we
evaluated the possible association between AAP use and the severity of OSA.
METHODS: A sample of patients using AAP for treatment of paradoxical insomnia was
evaluated before and at least 8 weeks after AAP use. Patients were divided based
on type of AAP use to olanzapine, risperidone, and quetiapine groups. Patients
used olanzapine (5-10 mg), risperidone (2-4 mg), or quetiapine (100-200 mg) 2 h
before bedtime. Before and after treatment, respiratory variables were recorded
using polysomnography. BMI, neck circumference (NC), and waist circumference (WC)
were measured before and after treatment period. RESULTS: There was no
significant difference between pre- and post-treatment apnea index (0.2 +/- 0.6
vs. 2.6 +/- 4.3; p = 0.094) in olanzapine group. However, significant differences
in hypopnea index (5.1 +/- 5 vs. 30 +/- 10.8; p < 0.0001) and AHI (5.3 +/- 4.9
vs. 32.6 +/- 9.6; p < 0.0001) were observed. Similar results were found in
quetiapine and risperidone groups, except that in quetiapine group, apnea index
was significantly increased after treatment period (0.7 +/- 1.2 in pre-treatment
vs. 3.1 +/- 2.4 in post-treatment; p = 0.007). There were no significant changes
in BMI, NC, and WC during treatment period in all three groups. CONCLUSION: While
AAP medications are known cause of weight gain as a main risk factor of OSA, our
finding demonstrated a weight-independent association between AAP medications and
worsening respiration during sleep.
PMID- 28707162
TI - Pulmonary surfactant-associated proteins and inflammatory factors in obstructive
sleep apnea.
AB - PURPOSE: Pulmonary surfactant (PS) plays roles in promoting the removal of the
liquid, host defense, and immune regulation in the tracheal, bronchial, and
alveoli epithelium. PS protein expression level can be regulated by oxygen levels
and related free radicals. Obstructive sleep apnea (OSA) is featured with oxygen
free radical production for damaging epithelial tissues and thus may affect PS
production. The study was to explore the relationship between PS protein and OSA
severity. METHODS: We collected serum and bronchoalveolar lavage fluid (BALF)
samples from 35 OSA patients and 22 healthy subjects. PS-associated proteins and
inflammatory factors, including surfactant proteins, HIF-1alpha, NF-kappaB, and
IL-6, were analyzed. Regression analysis was performed to reveal the relationship
between biochemical factors and clinical indexes recorded during PSG monitor.
RESULTS: Lower BALF and surfactant protein (except surfactant protein C or SPC)
levels occurred in OSA patients (all p < 0.05 compared to control group). A
strongly negative correlation was found between surfactant protein with apnea
hypopnea index (AHI) and other sleeping indexes including ODI3 and ODI4. Similar
patterns were found in serum samples, which were strongly correlated with BALF
counterparts. Surfactant proteins were further found to have negative regression
with inflammatory factors such as HIF-1alpha, NF-kappaB, and IL-6. CONCLUSIONS:
This study established the relationship between PS-related protein with severity
of OSA, plus their relationship with inflammatory factors. Our results provided
possibly novel markers in general circulation for disease evaluation of OSA.
PMID- 28707163
TI - Characterization of SNPs in the dopamine-beta-hydroxylase gene providing new
insights into its structure-function relationship.
AB - Dopamine-beta-hydroxylase (DBH, EC 1.14.17.1), an oxido-reductase that catalyses
the conversion of dopamine to norepinephrine, is largely expressed in sympathetic
neurons and adrenal medulla. Several regulatory and structural variants in DBH
associated with various neuropsychiatric, cardiovascular diseases and a few that
may determine enzyme activity have also been identified. Due to paucity of
studies on functional characterization of DBH variants, its structure-function
relationship is poorly understood. The purpose of the study was to characterize
five non-synonymous (ns) variants that were prioritized either based on previous
association studies or Sorting Tolerant From Intolerant (SIFT) algorithm. The DBH
ORF with wild type (WT) and site-directed mutagenized variants were transfected
into HEK293 cells to generate transient and stable lines expressing these variant
enzymes. Activity was determined by UPLC-PDA and corresponding quantity by MRMHR
on a TripleTOF 5600 MS respectively of spent media from stable cell lines.
Homospecific activity computed for the WT and variant proteins showed a marginal
decrease in A318S, W544S and R549C variants. In transient cell lines,
differential secretion was observed in the case of L317P, W544S and R549C.
Secretory defect in L317P was confirmed by localization in ER. R549C exhibited
both decreased homospecific activity and differential secretion. Of note, all the
variants were seen to be destabilizing based on in silico folding analysis and
molecular dynamics (MD) simulation, lending support to our experimental
observations. These novel genotype-phenotype correlations in this gene of
considerable pharmacological relevance have implications for dopamine-related
disorders.
PMID- 28707164
TI - Optimizing the Bioavailability of Subcutaneously Administered Biotherapeutics
Through Mechanochemical Drivers.
AB - The subcutaneous route offers myriad benefits for the administration of
biotherapeutics in both acute and chronic diseases, including convenience, cost
effectiveness and the potential for automation through closed-loop systems.
Recent advances in parenteral administration devices and the use of additives
which enhance drug dispersion have generated substantial additional interest in
IV to SQ switching studies. Designing pre-clinical and clinical studies using SQ
mediated delivery however requires deep understanding of complex inter-related
physiologies and transport pathways governing the interstitial matrix, vascular
system and lymphatic channels. This expert review will highlight key structural
features which contribute to transport and biodistribution in the subcutaneous
space and also assess the impact of drug formulations. Based on the rapidly
growing interest in the SQ delivery route, a number of potential areas for future
development are highlighted, which are likely to allow continued evolution and
innovation in this important area.
PMID- 28707165
TI - Design, Preparation and Evaluation of HPMC-Based PAA or SA Freeze-Dried Scaffolds
for Vaginal Delivery of Fluconazole.
AB - PURPOSE: Aim of this work was preparation of bioadhesive gel formulations based
on Hydroxypropyl methylcellulose (HPMC), Poly(acrylic acid) (PAA) or Sodium
alginate (SA) loaded with anise/fluconazole beta-cyclodextrin inclusion complexes
in 1:2 and 1:3 ratios intended for vaginal applications. METHODS: Freeze-drying
method was effectively utilized and superporous morphology was obtained. The
superporous morphology of the lyophilized gels, dynamic water vapor sorption
measurements, drug release kinetics studies and their antimicrobial activities
are presented. RESULTS: HPMC content influences especially the
sorption/desorption behaviour of HPMC-based PAA gels and the morphology of the
gel formulations with fluconazole/beta-cyclodextrin inclusion complexes, due to
the interactions among the gel networks absorbing water molecules. It was found
that fluconazole release kinetics correspond to quasi-Fickian, Fickian diffusion
and non-Fickian mechanisms for the studied hydrogels. The tested vaginal
formulations with beta-cyclodextrin inclusion complexes exhibited selectivity
toward S. aureus ATCC 25923 and all tested Candida strains in comparison with the
gel formulation without beta-cyclodextrin. CONCLUSIONS: The fluconazole/beta
cyclodextrin inclusion complexes ensure a controlled release of fluconazole over
a few days, the highest amount of drug release (92%) being observed after 43 h.
These bioadhesive gel formulations could be very promising topical alternative
for treatment of vaginal fungal infections.
PMID- 28707166
TI - Altered dynamic functional connectivity in the default mode network in patients
with cirrhosis and minimal hepatic encephalopathy.
AB - PURPOSE: Abnormal brain intrinsic functional connectivity (FC) has been
documented in minimal hepatic encephalopathy (MHE) by static connectivity
analysis. However, changes in dynamic FC (dFC) remain unknown. We aimed to
identify altered dFC within the default mode network (DMN) associated with MHE.
METHODS: Resting-state functional MRI data were acquired from 20 cirrhotic
patients with MHE and 24 healthy controls. DMN seed regions were defined using
seed-based FC analysis (centered on the posterior cingulate cortex (PCC)).
Dynamic FC architecture was calculated using a sliding time-window method. K
means clustering (number of clusters = 2-4) was applied to estimate FC states.
RESULTS: When the number of clusters was 2, MHE patients presented weaker
connectivity strengths compared with controls in states 1 and 2. In state 1,
decreased FC strength was found between the PCC/precuneus (PCUN) and right medial
temporal lobe (MTL)/bilateral lateral temporal cortex (LTC); left inferior
parietal lobule (IPL) and right MTL/left LTC; right IPL and right MTL/bilateral
LTC; right MTL and right LTC; and medial prefrontal cortex (MPFC) and right
MTL/bilateral LTC. In state 2, reduced FC strength was observed between the
PCC/PCUN and bilateral MTL/bilateral LTC; left IPL and left MTL/bilateral
LTC/MPFC; and left LTC and right LTC. Altered connectivities from state 1 were
correlated with patient cognitive performance. Similar findings were observed
when the number of clusters was set to 3 or 4. CONCLUSION: Aberrant dynamic DMN
connectivity is an additional characteristic of MHE. Dynamic connectivity
analysis offers a novel paradigm for understanding MHE-related mechanisms.
PMID- 28707167
TI - Supportive care for patients undergoing immunotherapy.
AB - Immune checkpoint inhibitors, a new class of cancer therapeutic agents, play an
important role in the management of melanoma, NSCLC, and other malignancies. A
workshop organized by three MASCC Study Groups: Oral Care, Skin Toxicities, and
Neutropenia, Infection, and Myelosuppression during the MASCC Annual Meeting held
in Adelaide, Australia on 23-25 June, 2016 focused on the new class of anti
cancer therapeutic agents. Topics in the workshop included the mechanism of
action and clinical uses of immune anti-CTL4 and anti-PD1 antibodies, checkpoint
inhibitor toxicities, including skin adverse events, gastrointestinal toxicities,
oral complications, pulmonary toxicities, and endocrinological and immune-related
infections. Checkpoint inhibitors have been approved for use in different
malignancies including metastatic melanoma, advanced non-small cell lung cancer,
metastatic renal cell carcinoma, refractory Hodgkin's lymphoma, metastatic
bladder cancer, and advanced head and neck cancer, and the list continues to
grow. In general, these agents seem to be better tolerated in most patients and
less toxic compared to conventional chemotherapy. However, the toxicities here,
termed immune-related adverse events (irAEs), are unique and different from what
we have seen in the past. There is no prospective data on these toxicities, and
guidelines or recommendations are currently based on symptomatic management from
the ongoing clinical trials. Treating oncologists need to be aware and alert
themselves to the subtleties in presentation and the big difference in the way we
manage the irAEs. Although most irAEs are low-grade and manageable, they have the
potential to be life-threatening and extremely severe if not promptly treated.
Additionally, irAEs could even lead to death, if managed incorrectly. The MASCC
workshop addressed the various irAEs, per organ system, clinical presentation,
management recommendations, and individual toxicities.
PMID- 28707168
TI - Acupuncture for cancer-related fatigue in lung cancer patients: a randomized,
double blind, placebo-controlled pilot trial.
AB - BACKGROUND: Cancer-related fatigue (CRF) is a distressing symptom that is the
most common unpleasant side effect experienced by lung cancer patients and is
challenging for clinical care workers to manage. METHODS: We performed a
randomized, double-blind, placebo-controlled pilot trial to evaluate the clinical
effect of acupuncture on CRF in lung cancer patients. Twenty-eight patients
presenting with CRF were randomly assigned to active acupuncture or placebo
acupuncture groups to receive acupoint stimulation (LI-4, Ren-6, St-36, KI-3, and
Sp-6) twice per week for 4 weeks, followed by 2 weeks of follow-up. The primary
outcome was the change in intensity of CFR based on the Chinese version of the
Brief Fatigue Inventory (BFI-C). As the secondary endpoint, the Functional
Assessment of Cancer Therapy-Lung Cancer Subscale (FACT-LCS) was adopted to
assess the influence of acupuncture on patients' quality of life (QOL). Adverse
events and safety of treatments were monitored throughout the trial. RESULTS: Our
pilot study demonstrated feasibility among patients with appropriate inclusion
criteria and good compliance with acupuncture treatment. A significant reduction
in the BFI-C score was observed at 2 weeks in the 14 participants who received
active acupuncture compared with those receiving the placebo (P < 0.01). At week
6, symptoms further improved according to the BFI-C (P < 0.001) and the FACT-LCS
(P = 0.002). There were no significant differences in the incidence of adverse
events in either group (P > 0.05). CONCLUSION: Fatigue is a common symptom
experienced by lung cancer patients. Acupuncture may be a safe and feasible
optional method for adjunctive treatment in cancer palliative care, and
appropriately powered trials are warranted to evaluate the effects of
acupuncture.
PMID- 28707169
TI - Living with a peripherally inserted central catheter: the perspective of cancer
outpatients-a qualitative study.
AB - PURPOSE: The aim of this study was to describe the experience of using a
peripherally inserted central catheter (PICC) in cancer sufferers receiving
outpatient treatment. METHODS: A qualitative, phenomenological study was
performed. Purposeful sampling methods were used. Data collection methods
included semi-structured interviews and researcher field notes. Thematic analysis
was used to analyze data. The study was conducted following the Consolidated
Criteria for Reporting Qualitative Research guidelines. RESULTS: Eighteen
patients (61% women, mean age 58 years) participated. They spent a mean duration
of 155 days with the line in place. Two themes were identified with different
subgroups. The theme "Living with a PICC line," including the subthemes
"Benefits" and "Disadvantages," displays how the implantation is experienced by
patients in a dichotomous manner. This highlighted both the beneficial and
negative aspects of the implantation. The second theme was "Adapting to life with
the catheter" and comprised three subthemes: "Advantages," "Lifestyle
modifications," and "Overall assessment of the peripherally inserted central
catheter," which shows how patients gradually accept the catheter by adapting
their lifestyle. CONCLUSIONS: Over time, most patients considered having a PICC
line to be a positive experience that they would recommend to other patients, as
they found that it did not alter their quality of life. These results can be
applied in Oncology Units for developing specific protocols for patients.
PMID- 28707170
TI - Effectiveness and risk of biliary drainage prior to pancreatoduodenectomy: review
of current status.
AB - Preoperative biliary drainage (PBD) prior to pancreatoduodenectomy (PD) has
gained popularity as bridge management to resolve jaundice, but its role is being
challenged as it is thought to increase morbidity. To clarify the current
recommendations for PBD prior to PD, we reviewed the literature, including all
relevant articles published in English up until December, 2015. There is
increasing evidence that PBD causes bile infection, which is related to the
morbidity of infectious complications. Results of transhepatic drainage are
poorer than those of endoscopic stenting, especially in an oncologic setting,
although it is still unclear whether metallic stents are superior to nasobiliary
drainage. PBD should be avoided whenever possible and performed only in selected
cases, such as the emergency setting, an inevitable long delay (>4 weeks) before
PD, and jaundice-related anorexia. Seemingly, transhepatic drainage should be
reserved for refractory cases if endoscopic drainage is not possible. Further
studies comparing endoscopic drainage techniques, such as metallic stents and
nasobiliary drainage, are required to assess the most effective technique of PBD.
Bile infection should be prevented by adequate antibiotic prophylaxis and treated
even in the absence of symptoms, and bile status should be assessed
systematically.
PMID- 28707171
TI - Optimal use of arterial grafts during current coronary artery bypass surgery.
AB - Multiple arterial grafting, including the use of the bilateral internal thoracic
arteries (ITAs), has strong benefits on patient clinical outcomes after coronary
artery bypass grafting (CABG) but is far from commonly accepted at present. We
reviewed the previous randomized and leading observational studies and assembled
an up-to-date profile on multiple arterial grafting. Many of the previous trials
successfully showed the beneficial effects of arterial grafting after CABG.
Although many of these were retrospective studies, the data presented, mostly
from world-famous surgeons, show that multiple arterial grafting does have
advantages with regard to the long-term patient outcome without increasing rates
of early mortality or morbidity. However, it is true that some surgeons
experience a certain amount of stress when using multiple arterial conduits.
Multiple arterial reconstruction has a strong advantage for patients undergoing
CABG and is now a standard worldwide strategy. Surgeons nowadays need to make
efforts to master arterial conduit techniques properly to provide state-of-the
art CABG to patients.
PMID- 28707172
TI - Long-Term Outcomes of Laparoscopic Sleeve Gastrectomy-a Single-Center,
Retrospective Study.
AB - INTRODUCTION: Sleeve gastrectomy (LSG) is one of the most popular bariatric
procedures. We present our long-term results regarding weight loss,
comorbidities, and gastric reflux disease. MATERIAL AND METHODS: We identified
patients who underwent LSG in our institution between 2006 and 2009. We revised
the data, and the patients with outdated contact details were tracked with the
national health insurance database and social media (facebook). Each of the
identified patients was asked to complete an online or telephone survey covering,
among others, their weight and comorbidities. On that basis, we calculated the
percent total weight loss (%TWL) and percent excess weight loss (%EWL), along
with changes in body mass index (DeltaBMI). Satisfactory weight loss was set at
>50% EWL (for BMI = 25 kg/m2). We evaluated type 2 diabetes (T2DM) and arterial
hypertension (AHT) based on the pharmacological therapy. GERD presence was
evaluated by the typical symptoms and/or proton pump inhibitor (PPI) therapy.
RESULTS: One hundred twenty-seven patients underwent LSG between 2006 and 2009.
One hundred twenty patients were qualified for this study. Follow-up data was
available for 100 participants (47 female, 53 male). Median follow-up period
reached 8.0 years (from 7.1 to 10.7). Median BMI upon qualification for LSG was
51.6 kg/m2. Sixteen percent of patients required revisional surgery over the
years (RS group), mainly because of insufficient weight loss (14 Roux-Y gastric
bypass-LRYGB; one mini gastric bypass, one gastric banding). For the LSG (LSG
group n = 84), the mean %EWL was 51.1% (+/-22.3), median %TWL was 23.5% (IQR 17.7
33.3%), and median DeltaBMI was 12.1 kg/m2 (IQR 8.2-17.2). Fifty percent (n = 42)
of patients achieved the satisfactory %EWL of 50%. For RS group, the mean %EWL
was 57.8% (+/-18.2%) and median %TWL reached 33% (IQR 27.7-37.9%). Sixty-two
percent (n = 10) achieved the satisfactory weight loss. Fifty-nine percent of
patients reported improvement in AHT therapy, 58% in T2DM. After LSG, 60% (n =
60) of patients reported recurring GERD symptoms and 44% were treated with proton
pomp inhibitors (PPI). In 93% of these cases, GERD has developed de novo.
CONCLUSIONS: Isolated LSG provides fairly good effects in a long-term follow-up
with mean %EWL at 51.1%. Sixteen percent of patients require additional surgery
due to insufficient weight loss. More than half of the subjects observe
improvement in AHT and T2DM. Over half of the patients complain of GERD symptoms,
which in most of the cases is a de novo complaint.
PMID- 28707173
TI - Intraoperative Ventilation of Morbidly Obese Patients Guided by Transpulmonary
Pressure.
AB - BACKGROUND: Bariatric surgery has proven a successful approach in the treatment
of morbid obesity and its concomitant diseases such as diabetes mellitus and
arterial hypertension. Aiming for optimal management of this challenging patient
cohort, tailored concepts directly guided by individual patient physiology may
outperform standardized care. Implying esophageal pressure measurement and
electrical impedance tomography-increasingly applied monitoring approaches to
individually adjust mechanical ventilation in challenging circumstances like
acute respiratory distress syndrome (ARDS) and intraabdominal hypertension-we
compared our institutions standard ventilator regimen with an individually
adjusted positive end expiratory pressure (PEEP) level aiming for a positive
transpulmonary pressure (P L) throughout the respiratory cycle. METHODS: After
obtaining written informed consent, 37 patients scheduled for elective bariatric
surgery were studied during mechanical ventilation in reverse Trendelenburg
position. Before and after installation of capnoperitoneum, PEEP levels were
gradually raised from a standard value of 10 cm H2O until a P L of 0 +/- 1 cm H2O
was reached. Changes in ventilation were monitored by electrical impedance
tomography (EIT) and arterial blood gases (ABGs) were obtained at the end of
surgery and 5 and 60 min after extubation, respectively. RESULTS: To achieve the
goal of a transpulmonary pressure (P L) of 0 cm H2O at end expiration, PEEP
levels of 16.7 cm H2O (95% KI 15.6-18.1) before and 23.8 cm H2O (95% KI 19.6
40.4) during capnoperitoneum were necessary. EIT measurements confirmed an
optimal PEEP level between 10 and 15 cm H2O before and 20 and 25 cm H2O during
capnoperitoneum, respectively. Intra- and postoperative oxygenation did not
change significantly. CONCLUSION: Patients during laparoscopic bariatric surgery
require high levels of PEEP to maintain a positive transpulmonary pressure
throughout the respiratory cycle. EIT monitoring allows for non-invasive
monitoring of increasing PEEP demand during capnoperitoneum. Individually
adjusted PEEP levels did not result in improved postoperative oxygenation.
PMID- 28707174
TI - Examining the Role of Microglia and Astroglia During the Pathogenesis of
Alzheimer's Disease via the Puri-Li Model.
AB - The Puri-Li kinetic model is explored here to study the contribution of microglia
and astroglia during the pathogenesis of Alzheimer's disease (AD). This is
carried out by solving the Puri-Li model under steady-state conditions. The
derived expressions show that both of them play a role in the pathogenesis of AD.
Examination of the steady-state solutions where microglia and astroglia are
involved shows that equilibrium conditions are achieved by microglia and
astroglia destroying neurons. These findings from this model are in agreement
with the results in the literature, where microglia and astroglia are considered
to act as inflammatory cells producing toxins to destroy neurons. In addition,
the study also showed that the number ratio of the total astroglial cells to the
total microglial cells increases with the progression of AD. With advances in
three dimensional imaging and selective staining, this ratio could be used as a
valuable marker to monitor AD.
PMID- 28707175
TI - Acculturation and Syndemic Risk: Longitudinal Evaluation of Risk Factors Among
Pregnant Latina Adolescents in New York City.
AB - Background: Syndemics are co-occurring epidemics that synergistically contribute
to specific risks or health outcomes. Although there is substantial evidence
demonstrating their existence, little is known about their change over time in
adolescents. Purpose: The objectives of this paper were to identify longitudinal
changes in a syndemic of substance use, intimate partner violence, and depression
and determine whether immigration/cultural factors moderate this syndemic over
time. Methods: In a cohort of 772 pregnant Latina adolescents (ages 14-21) in New
York City, we examined substance use, intimate partner violence, and depression
as a syndemic. We used longitudinal mixed-effect modeling to evaluate whether
higher syndemic score predicted higher syndemic severity, from pregnancy through
1 year postpartum. Interaction terms were used to determine whether immigrant
generation and separated orientation were significant moderators of change over
time. Results: We found a significant increasing linear effect for syndemic
severity over time (beta = 0.0413, P = 0.005). Syndemic score significantly
predicted syndemic severity (beta = -0.1390, P <= 0.0001), as did immigrant
generation (betaImmigrant = -0.1348, P <= 0.0001; beta1stGen = -0.1932, P =
0.0005). Both immigrant generation (betaImmigrant = -0.1125, P = 0.0035;
beta1stGen = -0.0135, P = 0.7279) and separated orientation (beta = 0.0946, P =
0.0299) were significantly associated with change in severity from pregnancy to 1
year postpartum. Conclusion: Pregnancy provides an opportunity for reducing
syndemic risk among Latina adolescents. Future research should explore syndemic
changes over time, particularly among high-risk adolescents. Prevention should
target syndemic risk reduction in the postpartum period to ensure that risk
factors do not increase after pregnancy.
PMID- 28707176
TI - Estimating the average need of semantic knowledge from distributional semantic
models.
AB - Continuous bag of words (CBOW) and skip-gram are two recently developed models of
lexical semantics (Mikolov, Chen, Corrado, & Dean, Advances in Neural Information
Processing Systems, 26, 3111-3119, 2013). Each has been demonstrated to perform
markedly better at capturing human judgments about semantic relatedness than
competing models (e.g., latent semantic analysis; Landauer & Dumais,
Psychological Review, 104(2), 1997 211; hyperspace analogue to language; Lund &
Burgess, Behavior Research Methods, Instruments, & Computers, 28(2), 203-208,
1996). The new models were largely developed to address practical problems of
meaning representation in natural language processing. Consequently, very little
attention has been paid to the psychological implications of the performance of
these models. We describe the relationship between the learning algorithms
employed by these models and Anderson's rational theory of memory (J. R. Anderson
& Milson, Psychological Review, 96(4), 703, 1989) and argue that CBOW is learning
word meanings according to Anderson's concept of needs probability. We also
demonstrate that CBOW can account for nearly all of the variation in lexical
access measures typically attributable to word frequency and contextual diversity
two measures that are conceptually related to needs probability. These results
suggest two conclusions: One, CBOW is a psychologically plausible model of
lexical semantics. Two, word frequency and contextual diversity do not capture
learning effects but rather memory retrieval effects.
PMID- 28707177
TI - Do people use category-learning judgments to regulate their learning of natural
categories?
AB - Although research has established that people can accurately judge how well they
have learned categories, no research has examined whether people use their
category-learning judgments (CLJs) to regulate their restudy of natural
categories. Thus, in five experiments we investigated the relationship between
people's CLJs and selections of categories for restudy. Participants first
attempted to learn natural categories (bird families; e.g., finches, grosbeaks,
and warblers) so that they could categorize new exemplars on a final test. After
this initial study phase, participants made a CLJ for each category and then
selected a subset of the categories for restudy. Across experiments, we also
manipulated several variables (e.g., selecting either three or nine categories,
or obtaining 30% vs. 80% performance on the final test) that were expected to
influence restudy selections. However, the manipulations typically had minimal
impact. More important, in all experiments we found an unexpected outcome: Some
participants tended to select the categories they judged to be most well learned
for restudy, and others tended to select those judged to be least well learned.
We discovered these qualitative differences in the use of CLJs to make restudy
selections by using post-hoc analyses in Experiments 1a and 1b, and hence we
sought to (a) replicate them in Experiments 2, 3, and 4 and (b) provide
preliminary evidence regarding factors that can (vs. cannot) account for them.
Most important, evidence across all of the experiments supported the conclusion
that people do use their CLJs to select categories for restudy.
PMID- 28707178
TI - Life-span retrieval of public events: Reminiscence bump for high-impact events,
recency for others.
AB - Although substantial evidence exists showing a reliable reminiscence bump for
personal events, data regarding retrieval distributions for public events have
been equivocal. The primary aim of the present study was to address life-span
retrieval distributions of different types of public events in comparison to
personal events, and to test whether the existing accounts of the bump can
explain the distribution of public events. We asked a large national sample to
report the most important, happiest, and saddest personal events and the most
important, happiest, saddest, most proud, most fearful, and most shameful public
events. We found a robust bump corresponding to the third decade of life for the
happiest and the most important positive but not for the saddest and most
important negative personal events. For the most important public events, a bump
emerged only for the two most frequently mentioned events. Distributions of
public events cued with emotions were marked by recency. These results point to
potential differences in retrieval of important personal and public events. While
the life-script framework well accounts for the findings regarding important
personal events, a chronologically retroactive search seem to guide retrieval of
public events. Reminiscence bump observed for the two public events suggest that
age-at-event affects recall of public events to the degree that the events are
high-impact ones that dominate nation's collective memory. Results provide
further evidence that the bump is not unitary and points to importance of event
type and memory elicitation method with regard to competing explanations of the
phenomenon.
PMID- 28707179
TI - The grades that clinical teachers give students modifies the grades they receive.
AB - Prior studies have shown a correlation between the grades students receive and
how they rate their teacher in the classroom. In this study, the authors probe
this association on clinical rotations and explore potential mechanisms. All In
Training Evaluation Reports (ITERs) for students on mandatory clerkship rotations
from April 1, 2013 to January 31, 2015 were matched with the corresponding
student's rating of their teacher (SRT). The date and time that ITERs and SRTs
were submitted was used to divide SRTs into those submitted before versus after
the corresponding ITER was submitted. Multilevel, mixed effects linear regression
was used to examine the association between SRT, ITER rating, and whether the
ITER was submitted before or after SRT. Of 2373 paired evaluations, 1098 (46.3%)
SRT were submitted before the teacher had submitted the ITER. There was a
significant interaction between explanatory variables: when ITER ratings had not
yet been submitted, the regression coefficient for this association was 0.25 (95%
confidence interval [0.17, 0.33], p < 0.001), whereas the regression coefficient
was significantly higher when ITER ratings were submitted prior to SRT (0.40
[0.31, 0.49], p < 0.001). Finding an association between SRT and ITER when
students do not know their ITER ratings suggests that SRTs can capture attributes
of effective teaching, but the effect modification when students have access to
their ITER rating supports grade satisfaction bias. Further studies are needed to
explain the mechanism of grade satisfaction and to identify other biases that may
impact the validity of SRT.
PMID- 28707180
TI - A Social Needs Assessment Tool for an Urban Latino Population.
AB - Unmet social needs contribute significantly to health outcomes, yet they are not
routinely assessed in health care settings. Identifying modifiable social needs
and feasible tools to assess them may improve health and decrease costs. We
conducted 18 focus groups with 115 participants, stratified by age (18-35, 36-64,
and 65+), ethnicity (Hispanic, non-Hispanic), and language (English, Spanish) to
explore priority social needs, images to depict social need categories, and
acceptability of a computer-based program to identify these needs. The top three
social need domains were access to care, health promoting behaviors, and family
responsibilities. Participants voiced diverse social needs with notable
differences across demographic groups. Both the 36-64 year old age groups and
Spanish-speaking Hispanic patients were disproportionately impacted by unmet
social needs. Perceptions regarding use of an interactive computer program to
assess social needs varied by age. Most participants noted that a tablet computer
was an acceptable venue to share social needs, though a tutorial may be needed
for patients in the 65 and older group. Lastly, participants' ranking of icons
were compiled to identify recognizable images of social need categories for those
with literacy challenges. Unmet social needs were identified across all groups.
This composite of information (priority social needs and images to represent
them) will allow for creation of a tailored social need screening tool within an
urban Hispanic population.
PMID- 28707181
TI - Expanded Medicaid Provides Access to Substance Use, Mental Health, and Physician
Visits to Homeless and Precariously Housed Persons.
AB - To describe the Medicaid costs associated with persons who are homeless or
unstably housed. A retrospective secondary data analysis linked Medicaid
recipient data with a statewide homeless management information system. A total
of 19,950 persons received a housing service between 2012 and 2015 including
14,136 persons with Medicaid. Five of the most frequent diagnoses were substance
abuse or mental health conditions in 42.83% of all diagnoses. The most frequent
service was outpatient mental health and emergency department physician services.
These costs totaled $166,653,689 with prescription drug costs at $62,800,463,
with a total cost of $672,242,449, averaging $14,632.42 per 12-month period per
person. The potential changes in Medicaid could lead to cost transfers or a
reduction in services. Recognizing these are significant costs by homeless and
unstably housed persons only, these high costs warrant the determination of
points in care where effective cost saving interventions may be employed.
PMID- 28707182
TI - Anti-inflammatory and antialgic actions of a nanoemulsion of Rosmarinus
officinalis L. essential oil and a molecular docking study of its major chemical
constituents.
AB - We evaluate the anti-inflammatory and antialgic potency of a nanoemulsion (NEORO)
containing the essential oil of Rosmarinus officinalis L. (EORO), which is
composed primarily of limonene, camphor and 1,8-cineole. The EORO and NEORO were
administered orally 30 min prior to starting the experiments. In a test of rat
paw oedema induced by carrageenan, NEORO was effective in doses of 498 ug/kg, and
it inhibited 46% of the maximum peak of the oedema; in a dose of 300 mg/kg, EORO
inhibited 50% of the maximum peak of the oedema. In an acetic acid-induced
writhing test, NEORO yielded a dose-dependent effect, and a dose of 830 ug/kg
inhibited 84% of the algesic process; a dose of 100 mg/kg of EORO inhibited 55%.
In an assay for H2S production in rat stomachs, a dose of 498 ug/kg of NEORO
inhibited H2S production in all of the measurement phases, and a dose of 100
mg/kg EORO inhibited 60% and influenced the effect of the ethanol significantly,
reducing the production of H2S. We suggest that NEORO potentiated the effect of
EORO, demonstrating effectiveness in doses 600 times lower than those applied
with EORO. Among the major compounds of EORO, the camphor molecule exhibited the
largest number of interactions with the therapeutic targets related to the
inflammatory process, suggesting that it is responsible for EORO's anti
inflammatory and antialgic effects. This work paves the way for future
investigations related to the therapeutic role of NEORO in the inflammation
process.
PMID- 28707183
TI - Downregulation of iNOS and elevation of cAMP mediate the anti-inflammatory effect
of glabridin in rats with ulcerative colitis.
AB - BACKGROUND: Alternative medicine is widely accepted by public and becoming an
attractive approach for treatment of various diseases. Glabridin (Gla), a major
flavonoid present in licorice root, was reported to have antioxidant and anti
inflammatory properties. OBJECTIVE: The study aimed to investigate the possible
protective role of Gla against dextran sulphate sodium (DSS)-induced ulcerative
colitis (UC) in rats and to clarify the molecular mechanisms underlying Gla
function. METHODS: Forty male Wistar rats were divided into control, colitis
group (rats received 5% DSS in drinking water for 7 days), Gla group (50 mg/kg,
orally, once daily), and sulfasalazine (SLZ) group (500 mg/kg, orally, once
daily). Each of Gla and SLZ was administered 1 week ahead of DSS and parallel
with its administration. RESULTS: Gla ameliorated the inflammatory alterations
induced by DSS. Gla group showed a reduction in colon concentration of tumor
necrosis factor-alpha (TNF-alpha) and a decreased colon myeloperoxidase activity
(MPO). Gla treatment downregulated inducible nitric oxide synthase (iNOS) gene
expression in rat colon with a decreased content of nitric oxide (NO). Gla also
increased cyclic AMP (cAMP) concentration in rat colon compared to colitis group.
Such findings were comparable to or even better than those obtained by SLZ
treatment. The histological features of UC such as ulceration and inflammatory
cell infiltrations were improved in rat group treated by Gla. CONCLUSION: Gla
proved a potent anti-inflammatory role in UC through different mechanisms and,
being a natural product, it could be safely used as a protective measure in
inflammatory bowel diseases.
PMID- 28707184
TI - Misdiagnosis of tuberculosis associated with some species of nontuberculous
mycobacteria by GeneXpert MTB/RIF assay.
AB - Out of 12 nontuberculous mycobacteria (NTM) species, 5 were identified as
Mycobacterium tuberculosis (MTB) by GeneXpert at a bacterial load of 106.
Notably, two species, including M. abscessus and M. smegmatis, were flagged as
RIF-resistant MTB due to the high C(t) value of Probe E. In conclusion, our data
have demonstrated that the misdiagnosis of MTB by GeneXpert assay is observed in
five NTM species at a high bacterial load.
PMID- 28707185
TI - Trends in short-term and 1-year mortality in very elderly intensive care patients
in the Netherlands: a retrospective study from 2008 to 2014.
AB - PURPOSE: To describe the trends in short-term and long-term mortality in very
elderly intensive care unit (ICU) patients between 2008 and 2014. METHODS: A
retrospective cohort study was conducted using data from the National Intensive
Care Evaluation Foundation from 31 Dutch ICUs. Generalized linear mixed-effects
models were used to determine the change in adjusted short-term mortality
(ICU/hospital deaths) and long-term mortality (3, 6, and 12 months after ICU
admission) over the period 2008-2014 in very elderly patients and in patients
less than 80 years old admitted to the ICU. RESULTS: A total of 216,196 patients
admitted to 31 ICUs in the period from 2008 to 2014 were included in the study,
including 28,284 (13.1%) very elderly patients (80 years or older). Follow-up
data for determination of 3-, 6-, and 12-month mortality were available for,
respectively, 210,005 (97.1%), 202,551 (93.7%), and 176,847 (81.8%) ICU
admissions. The crude ICU and in-hospital mortality decreased, respectively, from
17.6% to 13.0% and from 30.7% to 21.0%. The annual risk-adjusted ICU and in
hospital mortality of very elderly patients (adjusted for APACHE III score,
comorbidities, and admission type) decreased significantly during the study
period [adjusted odds ratio 0.97 (0.95-0.99) and 0.92 (0.91-0.93), respectively].
Additionally, the annual risk-adjusted 3-, 6-, and 12-month mortality decreased
significantly from 2008 to 2014 [adjusted odds ratio 0.96 (0.95-0.97), 0.96 (0.94
0.97), and 0.97 (0.95-0.98), respectively]. A similar significant annual decrease
in risk-adjusted short-term and long-term mortality was observed in patients aged
less than 80 years. CONCLUSIONS: Both short-term and long-term risk-adjusted
mortality decreased significantly during the study period in both very elderly
ICU patients and patients aged less than 80 years in the Netherlands. This study
clearly shows that in our setting very elderly patients benefit almost as much as
their younger counterparts from improvement in quality of care over time.
PMID- 28707186
TI - Natural Oils for Skin-Barrier Repair: Ancient Compounds Now Backed by Modern
Science.
AB - Natural plant oils are commonly used as topical therapy worldwide. They are
usually easily accessible and are relatively inexpensive options for skin care.
Many natural oils possess specific compounds with antimicrobial, antioxidant,
anti-inflammatory, and anti-itch properties, making them attractive alternative
and complementary treatments for xerotic and inflammatory dermatoses associated
with skin-barrier disruption. Unique characteristics of various oils are
important when considering their use for topical skin care. Differing ratios of
essential fatty acids are major determinants of the barrier repair benefits of
natural oils. Oils with a higher linoleic acid to oleic acid ratio have better
barrier repair potential, whereas oils with higher amounts of irritating oleic
acid may be detrimental to skin-barrier function. Various extraction methods for
oils exist, including cold pressing to make unrefined oils, heat and chemical
distillation to make essential oils, and the addition of various chemicals to
simulate a specific scent to make fragranced oils. The method of oil processing
and refinement is an important component of selecting oil for skin care, and cold
pressing is the preferred method of oil extraction as the heat- and chemical-free
process preserves beneficial lipids and limits irritating byproducts. This review
summarizes evidence on utility of natural plant-based oils in dermatology,
particularly in repairing the natural skin-barrier function, with the focus on
natural oils, including Olea europaea (olive oil), Helianthus annus (sunflower
seed oil), Cocos nucifera (coconut oil), Simmondsia chinesis (jojoba oil), Avena
sativa (oat oil), and Argania spinosa (argan oil).
PMID- 28707188
TI - Hemodynamic Benefits of Counterpulsation, Implantable, Percutaneous, and
Intraaortic Rotary Blood Pumps: An In-Silico and In Vitro Study.
AB - Mechanical circulatory support (MCS) devices have become a standard therapy for
heart failure (HF) patients. MCS device designs may differ by level of support,
inflow and/or outflow cannulation sites, and mechanism(s) of cardiac unloading
and blood flow delivery. Investigation and direct comparison of hemodynamic
parameters that help characterize performance of MCS devices has been limited. We
quantified cardiac and vascular hemodynamic responses for different types of MCS
devices. Continuous flow (CF) left ventricular (LV) assist devices (LVAD) with LV
or left atrial (LA) inlet, counterpulsation devices, percutaneous CF LVAD, and
intra-aortic rotary blood pumps (IARBP) were quantified using established
computer simulation and mock flow loop models. Hemodynamic data were analyzed on
a beat-to-beat basis at baseline HF and over a range of MCS support. Results
demonstrated that all LVAD greatly diminished vascular pulsatility (P) and LV
external work (LVEW). LVAD with LA inflow provided a greater reduction in LVEW
compared to LVAD with LV inflow, but at the potential risk for blood
stasis/thrombosis in the LV at high support. Counterpulsation provided greater
coronary flow (CoF) augmentation, but had a lower reduction in LVEW compared to
partial percutaneous LVAD support. IARBP diminished LVEW, but at the expense of
diminished CoF due to coronary steal. The hemodynamic benefits for each type of
mechanical circulatory support system are unique and clinical decisions on device
selection to maximize end organ perfusion and minimize invasiveness needs to be
considered for an individual patients' presentation.
PMID- 28707187
TI - Imaging in Vascular Access.
AB - This review examines four imaging modalities; ultrasound (US), digital
subtraction angiography (DSA), magnetic resonance imaging (MRI) and computed
tomography (CT), that have common or potential applications in vascular access
(VA). The four modalities are reviewed under their primary uses, techniques,
advantages and disadvantages, and future directions that are specific to VA.
Currently, US is the most commonly used modality in VA because it is cheaper
(relative to other modalities), accessible, non-ionising, and does not require
the use of contrast agents. DSA is predominantly only performed when an
intervention is indicated. MRI is limited by its cost and the time required for
image acquisition that mainly confines it to the realm of research where high
resolution is required. CT's short acquisition times and high resolution make it
useful as a problem-solving tool in complex cases, although accessibility can be
an issue. All four imaging modalities have advantages and disadvantages that
limit their use in this particular patient cohort. Current imaging in VA
comprises an integrated approach with each modality providing particular uses
dependent on their capabilities. MRI and CT, which currently have limited use,
may have increasingly important future roles in complex cases where detailed
analysis is required.
PMID- 28707189
TI - Cardio-oncology: Gaps in Knowledge, Goals, Advances, and Educational Efforts.
AB - Over the past 20 years, cancer treatments have become more effective, leading to
significant improvements in survival rates. However, anticancer drugs can have
several possible cardiovascular side effects; in particular, the development of
left ventricular dysfunction with chemoradiation therapy can negatively affect
patients' cardiac outcome, and can limit anticancer treatments. This is an
ongoing issue that will continue to persist, due to the ongoing development of
new antitumor agents with potential cardiotoxic effects, and the prolonged life
expectancy of long-term cancer survivors. Thus, the need for cooperation between
oncologists and cardiologists in the management of cancer patients has led to the
development of a new medical discipline-cardio-oncology-where the issue of
cardiotoxicity is a topic of intense interest and research. However, several
issues remain-the proper definition and diagnosis of cardiotoxicity, as well as
monitoring and treatment strategies. In this review, the current advances in
cardio-oncology, limitations of current approaches, and future research fields
will be discussed.
PMID- 28707190
TI - Novel porcine model for calcium oxalate stone formation.
AB - BACKGROUND: Mechanisms for calcium-based stone formation are not clearly
delineated. Porcine are the most anatomically and physiologically congruent
mammal to humans. Our objectives were to develop a cost-effective and easily
reproducible porcine model for the study of calcium-based nephrolithiasis.
METHODS: Crossbred male pigs (n = 16) were assigned randomly to one of the
following treatments: (1) control; (2) ethylene glycol (EG) + vitamin D (VD); (3)
EG + ammonium chloride (AC); (4) EG + gentamicin (G); (5) EG + Lasix; (6) EG + VD
+ AC; (7) EG + VD + G. Treatments were administered for 28 days; blood and urine
were collected on day 0, 14, and 28. At the endpoint of the study, renal tissue
was collected for gross and microscopic analysis of crystal stone formation and
inflammation. RESULTS: Stone-forming parameters were observed in serum and urine.
For control versus all other treatments, by day 28, serum BUN and creatinine were
less (P < 0.01), urinary creatinine, citrate and pH were greater (P < 0.01), and
urinary oxalate was less (P < 0.01). Histopathological analysis of H&E staining
and stone analysis revealed formation of calcium oxalate stones and crystal
formation within the renal cortex and medulla for all animals except control.
Nephrotoxicity was observed in one animal from treatment EG + G. CONCLUSIONS: The
treatments explored in this experiment provided novel examples of cost-effective
porcine models for the study of nephrolithiasis. EG + VD had the strongest
indicators of nephrolithiasis without nephrotoxicity.
PMID- 28707191
TI - Clostridium Difficile, Colitis, and Colonoscopy: Pediatric Perspective.
AB - PURPOSE OF THE REVIEW: Review tests available for detection of Clostridium
difficile (C. Diff) induced disease, including when such tests should be done in
children and how they should be interpreted. RECENT FINDINGS: Multiple tests are
available for detecting disease due to C. diff. These include colonoscopy and
stool analysis. Colonoscopy with biopsy is the most sensitive test for detecting
the presence of colitis. The toxins produced by the C. diff. (toxin A, toxin B,
and binary toxin) are the agents that cause injury and disease. Only toxin
producing C. diff. Strains will cause disease. Binary toxin by itself is not
thought to produce disease. Binary toxin causes disease in humans when present
with toxin A and B producing bacteria, and has been implicated with fulminant
life threatening disease. Stool analyses vary in sensitivity and specificity
depending on the assay used. The presence of toxin producing strains of C diff.
in the stool does not equate with disease. The presence of a toxin-producing
bacteria or toxins (A or B) only equates with disease if diarrhea or a diseased
colon (toxic megacolon, ileus, and sepsis) is present. Nucleic acid amplification
testing (NAAT), when used in the stool from patients with diarrhea, appears to be
the most efficient study to detect the gene that encodes for toxin A and B and
thus to diagnose C. diff.-induced disease. Infants have a high carriage rate of
C. diff. and are believed not to develop disease from it or its toxins. Infants
should not be tested for C. difficile. The NAAT is most specific when done on
patients with diarrhea with liquid stools. Testing for C. difficile should only
be done on patients with diarrhea. One can assume that a patient who has no
diarrhea and is not ill does not have C. diff.-induced disease. Treatment should
be limited to patients with diarrhea who test positive for C. diff. toxin (A or
B) or toxin-producing bacteria. Direct testing for binary toxin is not
commercially available. Binary toxin is only thought to cause disease in humans
when C. diff. toxin (A and B)-producing bacteria are present.
PMID- 28707192
TI - [Geriatrics or geriatricization of medicine : Quo vadis geriatrics?]
AB - This article examines the question whether and how geriatrics will change in the
future and whether in view of the demographic changes the trend will go more in
the direction of a further expansion of geriatrics or more towards a
geriatricization of individual specialist medical fields. The different
development of geriatrics in the individual Federal States can only be understood
historically and is absolutely problematic against the background of the new
hospital remuneration system. Geriatrics is a typical cross-sectional faculty and
still has demarcation problems with other faculties but has also not yet clearly
defined the core competence. This certainly includes the increasing acquisition
of decentralized joint treatment concepts and geriatric counselling services in
the future, in addition to the classical assessment instruments. Keywords in
association with this are: traumatology and othopedics of the elderly, geriatric
neurology and geriatric oncology. Interdisciplinary geriatric expertise is
increasingly being requested. Outpatient structures have so far not been
prioritized in geriatrics. An independent research is under construction and it
is gratifying that academic interest in geriatrics seems to be increasing and new
professorial chairs have been established. It is not possible to imagine our
hospital without geriatrics; however, there is still a certain imbalance between
the clearly increased number of geriatric hospital beds, the representation of
geriatrics in large hospitals (e.g. specialized and maximum care hospitals and
university clinics), the secure establishment in further education regulations
and the lack of a uniform nationwide concept of geriatrics.
PMID- 28707193
TI - Laser Pulse Width Dependence and Ionization Mechanism of Matrix-Assisted Laser
Desorption/Ionization.
AB - Ultraviolet laser pulses at 355 nm with variable pulse widths in the region from
170 ps to 1.5 ns were used to investigate the ionization mechanism of matrix
assisted laser desorption/ionization (MALDI) for matrices 2,5-dihydroxybenzoic
acid (DHB), alpha-cyano-4-hydroxycinnamic acid (CHCA), and sinapinic acid (SA).
The mass spectra of desorbed ions and the intensity and velocity distribution of
desorbed neutrals were measured simultaneously for each laser shot. These
quantities were found to be independent of the laser pulse width. A comparison of
the experimental measurements and numerical simulations according to the
multiphoton ionization, coupled photophysical and chemical dynamics (CPCD), and
thermally induced proton transfer models showed that the predictions of thermally
induced proton transfer model were in agreement with the experimental data, but
those of the multiphoton ionization model were not. Moreover, the predictions of
the CPCD model based on singlet-singlet energy pooling were inconsistent with the
experimental data of CHCA and SA, but were consistent with the experimental data
of DHB only when some parameters used in the model were adjusted to extreme
values. Graphical Abstract ?.
PMID- 28707194
TI - Regularization of Ill-Posed Point Neuron Models.
AB - Point neuron models with a Heaviside firing rate function can be ill-posed. That
is, the initial-condition-to-solution map might become discontinuous in finite
time. If a Lipschitz continuous but steep firing rate function is employed, then
standard ODE theory implies that such models are well-posed and can thus,
approximately, be solved with finite precision arithmetic. We investigate whether
the solution of this well-posed model converges to a solution of the ill-posed
limit problem as the steepness parameter of the firing rate function tends to
infinity. Our argument employs the Arzela-Ascoli theorem and also yields the
existence of a solution of the limit problem. However, we only obtain convergence
of a subsequence of the regularized solutions. This is consistent with the fact
that models with a Heaviside firing rate function can have several solutions, as
we show. Our analysis assumes that the vector-valued limit function v, provided
by the Arzela-Ascoli theorem, is threshold simple: That is, the set containing
the times when one or more of the component functions of v equal the threshold
value for firing, has zero Lebesgue measure. If this assumption does not hold, we
argue that the regularized solutions may not converge to a solution of the limit
problem with a Heaviside firing function.
PMID- 28707195
TI - The power of print reading: comics in the classroom.
AB - Evidence from neuroscience and psychological studies supporting benefits of print
reading over digital reading has recently been discussed in these columns (Perbal
2017 J. Cell Commun. Signal. 11:1-4). In the present commentary, I would like to
add my perspective as a Humanities educator, and build upon the idea that print
reading results in better comprehension, learning and communication. The
argumentation that is presented herein is based on a study performed in a French
Comics language class aimed at broadening students' knowledge and experience of
graphic novels, and providing them with a cultural representation in the foreign
language. The results that are discussed in this commentary indicate that upon
reading printed books students created connections for a more meaningful learning
experience, leading to personal growth and linguistic development. The impact
these graphic novels had on students' learning capacity and relationship to
reading was tremendous. The kinesthetic relationship with printed text was deeply
enriching and gratifying. The stimulatory effects on their imagination allowed
for a more creative reading, and a deeper comprehension, resulting in meaningful
communication.
PMID- 28707196
TI - Reversible Association of the Hemagglutinin Subcomplex, HA-33/HA-17 Trimer, with
the Botulinum Toxin Complex.
AB - Botulinum neurotoxin (BoNT) associates with nontoxic proteins, either a nontoxic
nonhemagglutinin (NTNHA) or the complex of NTNHA and hemagglutinin (HA), to form
M- or L-toxin complexes (TCs). Single BoNT and NTNHA molecules are associated and
form M-TC. A trimer of the 70-kDa HA protein (HA-70) attaches to the M-TC to form
M-TC/HA-70. Further, 1-3 arm-like 33- and 17-kDa HA molecules (HA-33/HA-17
trimer), consisting of 1 HA-17 protein and 2 HA-33 proteins, can attach to the M
TC/HA-70 complex, yielding 1-, 2-, and 3-arm L-TC. In this study, the purified 1-
and 2-arm L-TCs spontaneously converted into another L-TC species after acquiring
the HA-33/HA-17 trimer from other TCs during long-term storage and
freezing/thawing. Transmission electron microscopy analysis provided evidence of
the formation of detached HA-33/HA-17 trimers in the purified TC preparation.
These findings provide evidence of reversible association/dissociation of the M
TC/HA-70 complex with the HA-33/HA-17 trimers, as well as dynamic conversion of
the quaternary structure of botulinum TC in culture.
PMID- 28707197
TI - Quantum-like behavior without quantum physics I : Kinematics of neural-like
systems.
AB - Recently there has been much interest in the possible quantum-like behavior of
the human brain in such functions as cognition, the mental lexicon, memory, etc.,
producing a vast literature. These studies are both empirical and theoretical,
the tenets of the theory in question being mainly, and apparently inevitably,
those of quantum physics itself, for lack of other arenas in which quantum-like
properties are presumed to obtain. However, attempts to explain this behavior on
the basis of actual quantum physics going on at the atomic or molecular level
within some element of brain or neuronal anatomy (other than the ordinary quantum
physics that underlies everything), do not seem to survive much scrutiny.
Moreover, it has been found empirically that the usual physics-like Hilbert space
model seems not to apply in detail to human cognition in the large. In this paper
we lay the groundwork for a theory that might explain the provenance of quantum
like behavior in complex systems whose internal structure is essentially hidden
or inaccessible. The approach is via the logic obeyed by these systems which is
similar to, but not identical with, the logic obeyed by actual quantum systems.
The results reveal certain effects in such systems which, though quantum-like,
are not identical to the kinds of quantum effects found in physics. These effects
increase with the size of the system.
PMID- 28707198
TI - Platelet-targeted pharmacologic treatments as anti-cancer therapy.
AB - Platelets act as multifunctional cells participating in immune response,
inflammation, allergy, tissue regeneration, and lymphoangiogenesis. Among the
best-established aspects of a role of platelets in non-hemostatic or thrombotic
disorders, there is their participation in cancer invasion and metastasis. The
interaction of many different cancer cells with platelets leads to platelet
activation, and on the other hand platelet activation is strongly instrumental to
the pro-carcinogenic and pro-metastatic activities of platelets. It is thus
obvious that over the last years a lot of interest has focused on the possible
chemopreventive effect of platelet-targeted pharmacologic treatments. This
article gives an overview of the platelet-targeted pharmacologic approaches that
have been attempted in the prevention of cancer development, progression, and
metastasis, including the application of anti-platelet drugs currently used for
cardiovascular disease and of new and novel pharmacologic strategies. Despite the
fact that very promising results have been obtained with some of these approaches
in pre-clinical models, with the exclusion of aspirin, clinical evidence of a
beneficial effect of anti-platelet agents in cancer is however still largely
missing. Future studies with platelet-targeted drugs in cancer must carefully
deal with design issues, and in particular with the careful selection of
patients, and/or explore novel platelet targets in order to provide a solution to
the critical issue of the risk/benefit profile of long-term anti-platelet therapy
in the prevention of cancer progression and dissemination.
PMID- 28707199
TI - Radiation-induced inflammatory cascade and its reverberating crosstalks as
potential cause of post-radiotherapy second malignancies.
AB - The disease-free survival following radiotherapy is often limited by the
development of second/secondary cancers. This significant impediment to effective
cancer treatment implicated even in the modern-day radiotherapy needs to be
countered effectively. Critical analysis reveals that besides achieving effective
tumor control, radiotherapy elicits certain cellular and systemic inflammatory
events in tumor infiltrate, which remain relatively stable and tend to facilitate
"in-field" or "out of field" oncogenesis in due course of time. Acute pro
inflammatory cytokines generated as a result of radiation-induced oxidative
insult and DNA damage induce genetic instability that contributes to tumor
heterogeneity and plasticity. The reverberating crosstalks between radiation
targeted tumor and its microenvironment in turn initiate inflammatory loops that
feedback the immune system to manifest as systemic consequences. An "inflammatory
switchover" within the tumor microenvironment is thus induced by cumulative
radiation exposure, initiating pro-tumor events that can severely limit the
outcome of radiotherapy. Various pro-survival tumorigenic pathways activated as a
result regulate radiation-induced hypoxia, ECM remodeling,
angiogenesis/vasculogenesis, and immune suppression/evasion within the tumor
microenvironment. NF-kappaB, HIF and STAT are identified as central regulating
mediators among others that orchestrate inflammatory switchover from apoptosis
mediated tumor surveillance to radiation-induced carcinogenesis. Radiation
induced interleukins stimulate recruited macrophages and endothelial cells to
promote intravasation, which is further aided by release of chemokines favoring
extravasation and secondary site lesions. We hence propose that delineating the
inflammatory signaling network emanating from irradiation of complex tumor tissue
is critical for devising suitable therapeutic strategies to prevent post
radiotherapy second cancers or metastasis. Graphical Abstract ?.
PMID- 28707200
TI - The influence of platelet membranes on tumour cell behaviour.
AB - The significant role of platelets in the protection of tumour cells from immune
attack and shear forces and the promotion of tumour cell extravasation from the
bloodstream in the process of haematogenous metastasis have been extensively
studied. The role of platelets, and in particular platelet membranes, in the
promotion of a more metastatic phenotype in tumour cells is a more recent and,
therefore, less well-recognised area of research. This review article summarises
studies that have focused on the impact of tumour cell interactions with
platelets and platelet membranes on tumour cell behaviour in vitro and in vivo.
Furthermore, the gene expression changes that occur within tumour cells following
contact with platelet membranes are also extensively reviewed. Overall, the
interaction of platelet membranes with tumour cells results in a more invasive
phenotype and the promotion of epithelial to mesenchymal transition with our own
genetic studies revealing that matrix metalloproteinase-1, plasminogen activator
inhibitor-1 and interleukin-8 are globally upregulated in a range of tumour cell
lines.
PMID- 28707201
TI - Taking presentations seriously: Invoking narrative craft in academic talks.
PMID- 28707202
TI - Executive functioning impairment in women treated with chemotherapy for breast
cancer: a systematic review.
AB - PURPOSE: Women with breast cancer have reported adverse cognitive effects
following chemotherapy. Evidence is mixed on whether executive functioning is
particularly impaired in women treated with chemotherapy, in part due to the wide
range of tasks used to measure executive processes. We performed a systematic
review of the published literature to evaluate whether some subcomponents of
executive functioning are more vulnerable to impairment than others among breast
cancer survivors who had been treated with chemotherapy. METHODS: Studies
published as of April 2017 were identified using three electronic databases
(MEDLINE, PsycINFO, and Web of Science) and a manual search of relevant reference
lists. The methodological quality of included studies was assessed using a
checklist of predefined criteria. RESULTS: Of 1280 identified articles, a total
of 41 were included for review. Study findings were categorized into three
primary subdomains of executive functioning: inhibition, shifting, and updating.
Although there was heterogeneity in the neuropsychological measures used to
assess executive functioning, tests could be grouped into the subcomponents they
assessed. Inhibition appears relatively spared from the effects of chemotherapy,
whereas impairments in shifting and updating are more commonly found following
chemotherapy. CONCLUSIONS: Examination of subcomponents of executive functioning
is recommended to better characterize the nature of executive dysfunction in
women treated with chemotherapy. Future studies should include executive
functioning tasks of varying complexity, use of multiple tasks to increase
reliability, and alternative indices to capture performance, such as within
person variability.
PMID- 28707204
TI - Ode to the Unknown Mentor.
PMID- 28707203
TI - Evaluating cognitive complaints in breast cancer survivors with the FACT-Cog and
quantitative electroencephalography.
AB - PURPOSE: Targeted methods for evaluating cognitive dysfunction in breast cancer
survivors are needed to effectively address this important survivorship issue. To
address this need, we examined the validity of a self-report instrument (The
functional assessment of cancer therapy: cognitive function; FACT-Cog) regarding
correspondence with neuropsychological performance versus depression and
evaluated neurophysiological biomarkers of cognition and depressed mood in a
sample of breast cancer survivors several years from diagnosis. METHODS: This is
a cross-sectional study sample from the prospective observational Mind Body
Study. Recruited participants were breast cancer survivors at least 3 years from
cancer diagnosis who were part of a longitudinal cohort, and were without current
psychiatric disorder or history of a neurological or cognitive disorder at
baseline (after completion of primary cancer treatment). Exploratory analysis of
the FACT-Cog and quantitative electroencephalography (qEEG) were conducted, with
respect to their association with neuropsychological domain scores and depressive
symptoms as measured by the Beck Depression Inventory, 2nd edition (BDI-II).
RESULTS: Self-reported cognitive abilities and the impact of cognitive
dysfunction on quality of life were associated with memory function in addition
to depressive symptoms in our sample of breast cancer survivors. qEEG measures
exhibit differential patterns of association with neuropsychological performance
and mood. CONCLUSIONS: Our findings indicate that perceived cognitive abilities
and the impact of cognitive difficulties on quality of life are valid indicators
of objective cognitive function, independent of depressive symptoms.
Neurophysiological correlates of cognitive function and depressive symptoms
represent promising biomarkers of these behavioral difficulties in survivorship.
PMID- 28707205
TI - Knowledge and Preferences of Primary Care Providers in Delivering Head and Neck
Cancer Survivorship Care.
AB - Long-term care for head and neck cancer (HNC) survivors is complex and requires
coordination among multiple providers. Clinical practice guidelines highlight the
role of primary care providers (PCPs) in screening for secondary
cancer/recurrence, assessment of late/long-term side effects, and referrals for
appropriate specialty management of toxicity. However, these responsibilities may
be difficult to meet within the scope of primary care practice. We conducted this
study to explore preferences, comfort, and knowledge of PCPs in the care of HNC
survivors. We piloted a 40-item web-based survey developed with oncologist and
PCP input targeted for family medicine and internal medicine providers. Responses
were collected within a single university health system over 2 months. PCPs (n =
28; RR = 11.3%) were interested in learning about health promotion after cancer
treatment (89%) and generally agree that their current practice patterns address
healthy lifestyle behaviors (82%). However, only 32% of PCPs felt confident they
could manage late/long-term side effects of chemotherapy, radiation, or surgery.
Only 29% felt confident they could provide appropriate cancer screening. Looking
at shared care responsibilities with oncology providers, PCPs perceived being
responsible for 30% of care in the first year after treatment and 81% of care
after 5 years. Seventy-one percent of PCPs agreed that oncologists provided them
necessary information, yet 32% of PCPs found it difficult to coordinate with
cancer providers. While these PCPs perceive increased care responsibility for
long-term survivors, most are uncomfortable screening for recurrence and managing
late/long-term side effects. Education and mutual coordination between PCPs and
oncology providers may improve survivor care.
PMID- 28707206
TI - Patients' Perception of App-based Educational and Behavioural Interventions for
Enhancing Oral Anticancer Medication Adherence.
AB - Well-designed smartphone apps can potentially help in enhancing adherence to oral
anticancer medications (OAMs). The objective of this study was to evaluate
patients' perception on inclusion of various adherence-enhancing strategies as
features of an app and their interest in using such app. A cross-sectional survey
was conducted at the National Cancer Centre Singapore. A structured self
administered questionnaire was used to collect data from patients taking OAMs.
Final analysis was based on 409 surveys and most of the respondents were female
(291, 71.1%), Chinese (332, 81.2%), married (296, 72.4%) and breast cancer
patients (211, 51.6%). Close to two-thirds of respondents rated medication
information (65.0%), disease information (60.2%) and side effect self-management
(60.2%) features as having the highest level of importance in an adherence app.
Three hundred thirty-two (81.2%) of the respondents owned a smartphone, among
which 92 (27.7%) reported using health-related apps. From respondents with
smartphones, 219 (66.0%) were interested in using an app for OAM adherence. Age
65 and older compared to 21-54 years old (adjusted OR = 0.34; 95% CI = 0.15-0.76)
and current use of a health app (adjusted OR = 1.91; 95% CI = 1.07-3.41) were
significant predictors of interest to adopt an adherence app. In conclusion,
patients value the inclusion of educational and behavioural interventions in
adherence apps. Developers of adherence apps should consider including tools for
side effect self-management and provision of information to educate patients on
their medications and disease condition.
PMID- 28707207
TI - Why published research is untrustworthy.
PMID- 28707208
TI - Opportunistic salpingectomy during vaginal hysterectomy for a benign pathological
condition.
AB - INTRODUCTION AND HYPOTHESIS: The objective was to evaluate the surgical
feasibility of opportunistic salpingectomy or salpingo-oophorectomy during benign
vaginal hysterectomy (HV) and the prevalence of occult tubal lesions. METHODS: In
this prospective study from 1 September 2013 to 1 November 2015, the prevalence
of bilateral salpingectomy with or without ovariectomy and the prevalence of
histopathological and immunohistochemical tubal abnormalities were assessed.
RESULTS: A total 115 patients were included. Bilateral salpingectomy was
performed in 85 patients (73.92%; group A) and was technically impossible in 30
patients (26.08%; group B). Older patients (62.9 vs 57.5 years, p = 0.009),
menopausal status (83.33% vs 62.35%, p = 0.03) and elevated BMI (27.58 vs 25.05 p
= 0.03) were statistically associated with failure of salpingectomy. There was
only one case of postoperative hemorrhage in group A. There was no difference
with regard to intra- or postoperative complications, blood loss, and operating
time between the two groups. Among the 67 fallopian tubes analyzed with a
validated histopathological protocol, there were 8 (11.94%) immunohistochemical
abnormalities with a "p53 signature." CONCLUSIONS: With the recent demonstration
of a tubal origin of most ovarian cancer, opportunistic salpingectomy could be a
theoretically relevant prevention strategy. Bilateral salpingectomy could be
performed during benign vaginal hysterectomy by experienced surgeons. The
advantages and disadvantages of exclusive salpingectomy during pelvic floor
surgery should be discussed with the patients.
PMID- 28707209
TI - Anaesthetic Preparation of Obese Patients: Current Status on Optimal Work-up.
AB - PURPOSE OF REVIEW: With the prevalence of obesity rapidly growing, bariatric
anaesthesia becomes everyday anaesthesia rather than a subspecialty. In this
review, we are aiming to draw attention to this complex group of patients and
their comorbidities, relevant to everyday practice for contemporary
anaesthetists. RECENT FINDINGS: We wanted to focus greatly on sleep-related
breathing disorders, because preoperative screening, diagnosis and treatment of
the aforementioned make a huge impact in the improvement of preoperative
morbidity and mortality, including positive effects on the cardiovascular system.
The overview is touching on main obesity-related comorbidities and guides the
anaesthetist and associated health professionals on how to approach and manage
them. A multidisciplinary approach widely used in bariatric care may be adopted
in the care of obese patients in order to reduce preoperative morbidity and
mortality. We advocate the early involvement of the anaesthetic team in the
preoperative assessment of obese patients in order to achieve appropriate risk
stratification and optimise the care.
PMID- 28707210
TI - Sparse Exploratory Factor Analysis.
AB - Sparse principal component analysis is a very active research area in the last
decade. It produces component loadings with many zero entries which facilitates
their interpretation and helps avoid redundant variables. The classic factor
analysis is another popular dimension reduction technique which shares similar
interpretation problems and could greatly benefit from sparse solutions.
Unfortunately, there are very few works considering sparse versions of the
classic factor analysis. Our goal is to contribute further in this direction. We
revisit the most popular procedures for exploratory factor analysis, maximum
likelihood and least squares. Sparse factor loadings are obtained for them by,
first, adopting a special reparameterization and, second, by introducing
additional [Formula: see text]-norm penalties into the standard factor analysis
problems. As a result, we propose sparse versions of the major factor analysis
procedures. We illustrate the developed algorithms on well-known psychometric
problems. Our sparse solutions are critically compared to ones obtained by other
existing methods.
PMID- 28707211
TI - High-accuracy drilling with an image guided light weight robot: autonomous versus
intuitive feed control.
AB - PURPOSE: Assistance of robotic systems in the operating room promises higher
accuracy and, hence, demanding surgical interventions become realisable (e.g. the
direct cochlear access). Additionally, an intuitive user interface is crucial for
the use of robots in surgery. Torque sensors in the joints can be employed for
intuitive interaction concepts. Regarding the accuracy, they lead to a lower
structural stiffness and, thus, to an additional error source. The aim of this
contribution is to examine, if an accuracy needed for demanding interventions can
be achieved by such a system or not. METHODS: Feasible accuracy results of the
robot-assisted process depend on each work-flow step. This work focuses on the
determination of the tool coordinate frame. A method for drill axis definition is
implemented and analysed. Furthermore, a concept of admittance feed control is
developed. This allows the user to control feeding along the planned path by
applying a force to the robots structure. The accuracy is researched by drilling
experiments with a PMMA phantom and artificial bone blocks. RESULTS: The
described drill axis estimation process results in a high angular repeatability
([Formula: see text]). In the first set of drilling results, an accuracy of
[Formula: see text] at entrance and [Formula: see text] at target point excluding
imaging was achieved. With admittance feed control an accuracy of [Formula: see
text] at target point was realised. In a third set twelve holes were drilled in
artificial temporal bone phantoms including imaging. In this set-up an error of
[Formula: see text] and [Formula: see text] was achieved. CONCLUSION: The results
of conducted experiments show that accuracy requirements for demanding procedures
such as the direct cochlear access can be fulfilled with compliant systems.
Furthermore, it was shown that with the presented admittance feed control an
accuracy of less then [Formula: see text] is achievable.
PMID- 28707212
TI - Automatic evaluation of vessel diameter variation from 2D X-ray angiography.
AB - PURPOSE: Early detection of blood vessel pathologies can be made through the
evaluation of functional and structural abnormalities in the arteries, including
the arterial distensibility measure. We propose a feasibility study on computing
arterial distensibility automatically from monoplane 2D X-ray sequences for both
small arteries (such as coronary arteries) and larger arteries (such as the
aorta). METHODS: To compute the distensibility measure, three steps were
developed: First, the segment of an artery is extracted using our graph-based
segmentation method. Then, the same segment is tracked in the moving sequence
using our spatio-temporal segmentation method: the Temporal Vessel Walker.
Finally, the diameter of the artery is measured automatically at each frame of
the sequence based on the segmentation results. RESULTS: The method was evaluated
using one simulated sequence and 4 patients' angiograms depicting the coronary
arteries and three depicting the ascending aorta. Results of the simulated
sequence achieved a Dice index of 98%, with a mean squared error in diameter
measurement of [Formula: see text] mm. Results obtained from patients' X-ray
sequences are consistent with manual assessment of the diameter by experts.
CONCLUSIONS: The proposed method measures changes in diameter of a specific
segment of a blood vessel during the cardiac sequence, automatically based on
monoplane 2D X-ray sequence. Such information might become a key to help
physicians in the detection of variations of arterial stiffness associated with
early stages of various vasculopathies.
PMID- 28707213
TI - Non-dominant hand use increases completion time on part B of the Trail Making
Test but not on part A.
AB - The Trail Making Test (TMT) is used in neuropsychological clinical practice to
assess aspects of attention and executive function. The test consists of two
parts (A and B) and requires drawing a trail between elements. Many patients are
assessed with their non-dominant hand because of motor dysfunction that prevents
them from using their dominant hand. Since drawing with the non-dominant hand is
not an automatic task for many people, we explored the effect of hand use on TMT
performance. The TMT was administered digitally in order to analyze new outcome
measures in addition to total completion time. In a sample of 82 healthy
participants, we found that non-dominant hand use increased completion times on
the TMT B but not on the TMT A. The average completion time increased by almost 5
seconds, which may be clinically relevant. A substantial number of participants
who performed the TMT with their non-dominant hand had a B/A ratio score of 2.5
or higher. In clinical practice, an abnormally high B/A ratio score may be
falsely attributed to cognitive dysfunction. With our digitized pen data, we
further explored the causes of the reduced TMT B performance by using new outcome
measures, including individual element completion times and interelement
variability. These measures indicated selective interference between non-dominant
hand use and executive functions. Both non-dominant hand use and performance of
the TMT B seem to draw on the same, limited higher-order cognitive resources.
PMID- 28707214
TI - Statistical and methodological problems with concreteness and other semantic
variables: A list memory experiment case study.
AB - The purpose of this article is to highlight problems with a range of semantic
psycholinguistic variables (concreteness, imageability, individual modality
norms, and emotional valence) and to provide a way of avoiding these problems.
Focusing on concreteness, I show that for a large class of words in the
Brysbaert, Warriner, and Kuperman (Behavior Research Methods 46: 904-911, 2013)
concreteness norms, the mean concreteness values do not reflect the judgments
that actual participants made. This problem applies to nearly every word in the
middle of the concreteness scale. Using list memory experiments as a case study,
I show that many of the "abstract" stimuli in concreteness experiments are not
unequivocally abstract. Instead, they are simply those words about which
participants tend to disagree. I report three replications of list memory
experiments in which the contrast between concrete and abstract stimuli was
maximized, so that the mean concreteness values were accurate reflections of
participants' judgments. The first two experiments did not produce a concreteness
effect. After I introduced an additional control, the third experiment did
produce a concreteness effect. The article closes with a discussion of the
implications of these results, as well as a consideration of variables other than
concreteness. The sensorimotor experience variables (imageability and individual
modality norms) show the same distribution as concreteness. The distribution of
emotional valence scores is healthier, but variability in ratings takes on a
special significance for this measure because of how the scale is constructed. I
recommend that researchers using these variables keep the standard deviations of
the ratings of their stimuli as low as possible.
PMID- 28707215
TI - Disentangling perceptual and psycholinguistic factors in syntactic processing:
Tone monitoring via ERPs.
AB - Franco, Gaillard, Cleeremans, and Destrebecqz (Behavior Research Methods, 47,
1393-1403, 2015), in a study on statistical learning employing the click
detection paradigm, conclude that more needs to be known about how this paradigm
interacts with statistical learning and speech perception. Past results with this
monitoring technique have pointed to an end-of-clause effect in parsing-a
structural effect-but we here show that the issues are a bit more nuanced.
Firstly, we report two Experiments (1a and 1b), which show that reaction times
(RTs) are affected by two factors: (a) processing load, resulting in a tendency
for RTs to decrease across a sentence, and (b) a perceptual effect which adds to
this tendency and moreover helps neutralize differences between sentences with
slightly different structures. These two factors are then successfully
discriminated by registering event-related brain potentials (ERPs) during a
monitoring task, with Experiment 2 establishing that the amplitudes of the N1 and
P3 components-the first associated with temporal uncertainty, the second with
processing load in dual tasks-correlate with RTs. Finally, Experiment 3
behaviorally segregates the two factors by placing the last tone at the end of
sentences, activating a wrap-up operation and thereby both disrupting the
decreasing tendency and highlighting structural effects. Our overall results
suggest that much care needs to be employed in designing click-detection tasks if
structural effects are sought, and some of the now-classic data need to be
reconsidered.
PMID- 28707216
TI - Imageability ratings across languages.
AB - Imageability is a psycholinguistic variable that indicates how well a word gives
rise to a mental image or sensory experience. Imageability ratings are used
extensively in psycholinguistic, neuropsychological, and aphasiological studies.
However, little formal knowledge exists about whether and how these ratings are
associated between and within languages. Fifteen imageability databases were
cross-correlated using nonparametric statistics. Some of these corresponded to
unpublished data collected within a European research network-the Collaboration
of Aphasia Trialists (COST IS1208). All but four of the correlations were
significant. The average strength of the correlations (rho = .68) and the
variance explained (R 2 = 46%) were moderate. This implies that factors other
than imageability may explain 54% of the results. Imageability ratings often
correlate across languages. Different possibly interacting factors may explain
the moderate strength and variance explained in the correlations: (1) linguistic
and cultural factors; (2) intrinsic differences between the databases; (3) range
effects; (4) small numbers of words in each database, equivalent words, and
participants; and (5) mean age of the participants. The results suggest that
imageability ratings may be used cross-linguistically. However, further
understanding of the factors explaining the variance in the correlations will be
needed before research and practical recommendations can be made.
PMID- 28707217
TI - Baseline glucoregulatory function moderates the effect of dairy milk and fruit
juice on postprandial cognition in healthy young adults.
AB - PURPOSE: Few studies have examined acute cognitive effects of dairy products.
Prior work suggests baseline glucoregulatory function may moderate the
relationship between macronutrient profile and postprandial cognition. This study
examined the role of glucoregulatory function in postprandial cognition after
milk, fruit juice, and a water control. We hypothesized juice would improve
cognition in those with lower fasting glucose, while milk would improve cognition
in those with higher fasting glucose. DESIGN: 86 non-diabetic, non-hypoglycemic
young adults attended three 8 AM testing sessions after fasting overnight.
Fasting glucose was assessed via fingerstick at each session. Participants
consumed 8 oz of 1% milk (12 g carbohydrates), apple juice (29 g carbohydrates),
or water in a randomized, counterbalanced order, and completed repeatable
standard and running memory continuous performance (SCPT-vigilance; RMCPT-working
memory) and go/no-go (GNG-inhibitory control) tasks 30, 90, and 120 min post
ingestion. RESULTS: Participants with fasting glucose above 107.69 mg/dL made
significantly fewer GNG commission errors overall after milk versus water, while
the converse was observed when fasting glucose was below 70.85 mg/dL (p = 0.003).
At 30 min, participants with fasting glucose above 105.80 mg/dL made
significantly more RMCPT correct responses per minute after milk versus juice,
while the opposite occurred when fasting glucose was below 76.85 mg/dL (p =
0.006). For both tasks, differences greatened as fasting glucose increased or
decreased beyond these upper and lower bounds, respectively. CONCLUSIONS:
Consideration of baseline glucoregulatory function is crucial when assessing
postprandial cognition, even in non-diabetic and non-hypoglycemic samples. Dairy
milk may improve cognition in persons with higher fasting glucose.
PMID- 28707218
TI - The DNA damage response pathway in normal hematopoiesis and malignancies.
AB - In mammalian cells, the DNA damage response (DDR) prevents the replication and
propagation of DNA errors to the next generation, thus maintaining genomic
stability. At the heart of the DDR are the related signaling kinases ATM, ATR,
and DNA-PK, which regulate DNA repair and associated events such as cell cycle
checkpoints, chromatin remodeling, transcription, and ultimately apoptosis.
Several findings highlight the occurrence of DDR in hemopoietic stem cells
(HSCs), and persistence of DNA lesions in these cells promotes their functional
decline and accumulation of leukemogenic mutations. Besides favoring tumor
formation and progression, molecular defects that directly or indirectly
inactivate certain DDR pathways can provide a therapeutic opportunity, since a
reduced ability to repair DNA lesions renders hemopoietic malignancies vulnerable
to genotoxic drugs acting also through synthetic lethal interactions. Here, we
discuss the essential role of DDR in HSC maintenance and protection against
leukemogenesis, and how acquired DDR dysfunctions or pharmacological agents that
block this pathway can be effectively exploited for the treatment of various
hematopoietic malignancies.
PMID- 28707219
TI - A Stochastic Tick-Borne Disease Model: Exploring the Probability of Pathogen
Persistence.
AB - We formulate and analyse a stochastic epidemic model for the transmission
dynamics of a tick-borne disease in a single population using a continuous-time
Markov chain approach. The stochastic model is based on an existing deterministic
metapopulation tick-borne disease model. We compare the disease dynamics of the
deterministic and stochastic models in order to determine the effect of
randomness in tick-borne disease dynamics. The probability of disease extinction
and that of a major outbreak are computed and approximated using the multitype
Galton-Watson branching process and numerical simulations, respectively.
Analytical and numerical results show some significant differences in model
predictions between the stochastic and deterministic models. In particular, we
find that a disease outbreak is more likely if the disease is introduced by
infected deer as opposed to infected ticks. These insights demonstrate the
importance of host movement in the expansion of tick-borne diseases into new
geographic areas.
PMID- 28707220
TI - Application of Quasi-Steady-State Methods to Nonlinear Models of Intracellular
Transport by Molecular Motors.
AB - Molecular motors such as kinesin and dynein are responsible for transporting
material along microtubule networks in cells. In many contexts, motor dynamics
can be modelled by a system of reaction-advection-diffusion partial differential
equations (PDEs). Recently, quasi-steady-state (QSS) methods have been applied to
models with linear reactions to approximate the behaviour of the full PDE system.
Here, we extend this QSS reduction methodology to certain nonlinear reaction
models. The QSS method relies on the assumption that the nonlinear binding and
unbinding interactions of the cellular motors occur on a faster timescale than
the spatial diffusion and advection processes. The full system dynamics are shown
to be well approximated by the dynamics on the slow manifold. The slow manifold
is parametrized by a single scalar quantity that satisfies a scalar nonlinear
PDE, called the QSS PDE. We apply the QSS method to several specific nonlinear
models for the binding and unbinding of molecular motors, and we use the
resulting approximations to draw conclusions regarding the parameter dependence
of the spatial distribution of motors for these models.
PMID- 28707221
TI - Modelling the Evolution of Traits in a Two-Sex Population, with an Application to
Grandmothering.
AB - We present a mathematical simplification for the evolutionary dynamics of a
heritable trait within a two-sex population. This trait is assumed to control the
timing of sex-specific life-history events, such as the age of sexual maturity
and end of female fertility, and each sex has a distinct fitness trade-off
associated with the trait. We provide a formula for the fitness landscape of the
population and show a natural extension of the result to an arbitrary number of
heritable traits. Our method can be viewed as a dynamical systems generalisation
of the Price equation to include two sexes, age structure and multiple traits. We
use this formula to examine the effect of grandmothering, whereby post-fertile
females subsidise their daughter's fertility by provisioning grandchildren.
Grandmothering can drive a shift towards increasingly male-biased mating sex
ratios due to a post-fertile life stage in females, while male fertility
continues to older ages. Our fitness landscapes show a net increase in fitness
for both males and females at longer lifespans, and as a result, we find that
grandmothering alone provides an evolutionary trajectory to higher longevities.
PMID- 28707222
TI - Considering the inferior surface area of lower lumbar vertebrae: determining
weight transmission pattern at the lumbosacral junction.
AB - The biomechanical function of the lumbosacral junction (LSJ) is obscure, but its
medical significance is not, as it is the most common site of low back pain. In
this study, we analyzed the difference between the mean values of the surface
areas of the inferior body and total inferior facet areas of the fourth and fifth
lumbar vertebrae. We aimed to define the function of the LSJ during weight
transmission and clarify its mechanical significance. Vertebral columns of 45
adult male human cadavers from five anatomy departments in Nigeria were cut at
the L3-L4 intervertebral disc and macerated. Using the graph paper method, the
mean values of the surface area of the inferior body and total facet area of the
fourth and fifth lumbar vertebrae were 1356 +/- 26 and 329 +/- 6 and 1277 +/- 27
and 418 +/- 8 mm2, respectively. The relationships between the fourth and fifth
lumbar vertebrae paired variables were highly significant (P < 0.001). A sudden
reduction in the surface area of the inferior body of the fifth lumbar vertebra
was compensated for by a corresponding increase in its total inferior facet area,
which indicated that corresponding weight was diverted from the anterior column
to the posterior column at the LSJ. This pattern of weight transmission may be a
beneficial functional adaptation in man to protect the relatively large
intervertebral disc of the LSJ in bipedal posture, or it may predispose the LSJ
synovial zygapophyseal joints to mechanical stress.
PMID- 28707223
TI - Inhibition of exendin-4-induced steatosis by protein kinase A in cultured HepG2
human hepatoma cells.
AB - Nonalcoholic fatty liver is characterized by the abnormal accumulation of
triglycerides within hepatocytes, resulting in a steatotic liver. Glucagon-like
peptide 1 and its analog exendin-4 can ameliorate certain aspects of this
syndrome by inducing weight loss and reducing hepatic triglyceride accumulation,
but it is unclear whether these effects result from the effects of glucagon-like
peptide 1 on the pancreas, or from direct action on the liver. This study
investigated the direct action and putative cellular mechanism of exendin-4 on
steatotic hepatocytes in culture. Steatosis was induced in cultured HepG2 human
hepatoma cells by incubation in media supplemented with 2 mM each of linoleic
acid and oleic acid. Steatotic hepatocytes were then pre-incubated in the protein
kinase A inhibitor H89 for 30 min, then treated with exendin-4 over a period of
24 h. Cell viability and triglyceride content were characterized by a TUNEL assay
and AdipoRed staining, respectively. Our results showed that steatotic cells
maintained high levels of intracellular triglycerides (80%) compared to lean
controls (25%). Exendin-4 treatment caused a significant reduction in
intracellular triglyceride content after 12 h that persisted through 24 h, while
protein kinase A inhibitors abolished the effects of exendin-4. The results
demonstrate the exendin-4 induces a partial reduction in triglycerides in
steatotic hepatocytes within 12 h via the GLP-1 receptor-mediated activation of
protein kinase A. Thus, the reduction in hepatocyte triglyceride accumulation is
likely driven primarily by downregulation of lipogenesis and upregulation of beta
oxidation of free fatty acids.
PMID- 28707224
TI - The influence of simulated microgravity on proliferation and apoptosis in U251
glioma cells.
AB - Several studies have indicated that microgravity can influence cellular
progression, proliferation, and apoptosis in tumor cell lines. In this study, we
observed that simulated microgravity inhibited proliferation and induced
apoptosis in U251 malignant glioma (U251MG) cells. Furthermore, expression of the
apoptosis-associated proteins, p21 and insulin-like growth factor binding protein
2 (IGFBP-2), was upregulated and downregulated, respectively, following exposure
to simulated microgravity. These findings indicate that simulated microgravity
inhibits proliferation while inducing apoptosis of U251MG cells. The associated
effects appear to be mediated by inhibition of IGFBP-2 expression and stimulation
of p21 expression. This suggests that simulated microgravity might represent a
promising method to discover new targets for glioma therapeutic strategy.
PMID- 28707225
TI - Establishment and characterization of a brain cell line from sea perch,
Lateolabrax japonicus.
AB - A continuous cell line, designated LJB, derived from the brain of sea perch
(Lateolabrax japonicus) was established. LJB cells have been subcultured for more
than 60 times in Dulbecco's modified Eagle's medium (DMEM) supplemented with 15%
fetal bovine serum (FBS) since the initial primary culture. LJB cells exhibited
maximum growth rate at 28 degrees C in DMEM supplemented with 20% FBS.
Cytogenetic analysis indicated that the modal chromosome number was 48, which was
identical with the chromosome number of embryonic stem-like cells of sea perch.
Comparison of the 18S ribosomal RNA gene sequences of LJB cells and sea perch
confirmed that LJB cells originated from sea perch. After transfected with pEGFP
N3 plasmid, LJB cells showed a transfection efficiency of about 40% which was
indicated by the percentage of cells expressing green fluorescence protein,
indicating the potential application of LJB cells in gene expression studies.
Cytopathic effect was clearly observed, and RNA-dependent RNA polymerase gene was
also detected in LJB cells post red-spotted grouper nervous necrosis virus
(RGNNV) infection. Furthermore, virus replication was confirmed by quantitative
RT-PCR, virus titer, and transmission electron microscopy assay in RGNNV-infected
LJB cells. The LJB cell line might be used as an ideal in vitro tool for
analyzing and understanding the mechanisms of nervous necrosis virus-host
interaction.
PMID- 28707227
TI - Snow white.
PMID- 28707226
TI - The role of macrophage polarization on fibroblast behavior-an in vitro
investigation on titanium surfaces.
AB - OBJECTIVES: This study investigated the effect of smooth and rough titanium
surface topographies on macrophage polarization and their influence on gingival
fibroblast behavior cultured on titanium surfaces. MATERIALS AND METHODS: RAW
264.7 macrophages were seeded on smooth (pickled titanium (PT)) and rough Sand
blasted with Large grit particles followed by Acid-etching (SLA) titanium
surfaces and first investigated for macrophage polarization towards tissue
inflammatory M1 macrophages or wound-healing M2 macrophages. Thereafter, culture
media collected from macrophages on both surfaces were cultured with gingival
fibroblasts seeded on their respective topographies. All experiments were
performed in triplicate with three independent experiments. RESULTS: Macrophages
seeded on SLA surfaces polarized towards tissue-inflammatory M1 macrophages at
early time points. Immunofluorescent staining and RT-PCR analysis demonstrated
higher levels of iNOS and gene expression of IL-1beta, IL-6, and TNF-alpha on SLA
surfaces at 3 days when compared to both tissue culture plastic (TCP) and PT
surfaces (p < 0.001). Very little differences were found between smooth PT
surfaces and TCP. Interestingly, proliferation assay (CCK-8) suggested that
conditioned media (CM) from macrophages seeded on SLA surfaces drastically
inhibited gingival fibroblast proliferation at 3 and 5 days (p < 0.001).
Meanwhile, CM from macrophages cultured on SLA surfaces also significantly
reduced collagen 1 synthesis on SLA surfaces at 14 days as assessed by
immunofluorescent staining (p < 0.001). CONCLUSION: The results from this study
demonstrate that the polarization of macrophages towards a pro-inflammatory (M1)
phenotype on SLA surfaces may have a negative impact on gingival fibroblast
behavior on titanium surfaces. Future strategies to better modulate macrophage
polarization should be investigated to support a favorable immune response and
encourage tissue integration. CLINICAL RELEVANCE: As SLA surfaces have a
potential to shift macrophages towards tissue-inflammatory M1 macrophages, this
might be a negative impact for soft tissue healing. Therefore, SLA surfaces
should be kept within the bone, as when in contact with soft tissue, they are
prone to support a lack of soft tissue integration leading to inflammation.
PMID- 28707228
TI - Snow white.
PMID- 28707229
TI - Antiplatelet therapy with CABG: chaos in the Netherlands.
PMID- 28707230
TI - Secondary Traumatic Stress in Medical Students.
PMID- 28707231
TI - A Medical Student-Run Child and Adolescent Psychiatry Clinic: One Institution's
Experience.
AB - OBJECTIVE: This report examines the experience of one institution's development
of the first student-run psychiatry clinic that serves both adult and pediatric
populations. METHODS: The clinic is held weekly with pre-clinical and clinical
medical student volunteers under the supervision of board-certified adult and
child psychiatrists. The development and evolution of the clinic over time are
evaluated with particular attention to obstacles overcome. Medical student
volunteers were surveyed retrospectively to evaluate their experience with
patients with psychiatric illness, skill development, and interest in psychiatry.
RESULTS: Since January 2016, the clinic has scheduled 90 patients, 32% of which
were pediatric patients. Ninety-six medical students have volunteered, with
roughly equal parts from all four medical school classes. Respondents to the
experience survey showed marked improvement in their comfort working with
patients with mental illness. Additionally, 40% "strongly agreed" or "agreed"
that their experience influenced their interest in pursuing psychiatry as a
career. CONCLUSION: This report describes a student-run psychiatry clinic with a
dual mission of education and service, and the challenges associated with these
sometimes competing goals. This clinic serves a vital need within our community
and may be an example of the role that student-run clinics can have in fostering
interdisciplinary care, psychiatric recruitment, and training for medical
students.
PMID- 28707232
TI - International Medical Graduates and American Psychiatry: The Past, Present, and
Future.
PMID- 28707233
TI - Inflammatory follicular cysts associated to necrotic primary teeth.
AB - BACKGROUND: Cysts are pathological cavities lined by epithelium and supported by
connective tissue, containing fluid or semi-fluid substances and presenting
developmental or inflammatory origins. CASE REPORT: This study aimed to evaluate
a case series of inflammatory follicular cysts in children to clarify their
nomenclature, diagnosis, clinical implications and treatment outcomes.
Prevalence, aetio-pathogenesis, clinical, radiographic and microscopic findings,
treatments and sequelae of this condition were assessed by using the records of
patients treated between 2000 and 2015. Data were analysed and presented
descriptively. FOLLOW-UP: This was performed periodically for 2 years to monitor
lesion regression and complete eruption of impacted permanent teeth. All of the
involved permanent teeth erupted naturally. Twelve cases of asymptomatic lesions
with volumetric bone expansion were identified through radiographic findings or
delayed tooth eruption in patients aged between 8 and 14 years. After
establishing the diagnosis of inflammatory follicular cyst, necrotic primary
teeth extraction was followed by decompression of the cystic lesions.
CONCLUSIONS: The investigated cases were consistent with inflammatory follicular
cyst diagnoses. The proposed treatment was considered to be appropriate, that was
revealed by the maintenance of the permanent teeth involved during the patients
follow-up.
PMID- 28707234
TI - The Elusive Search for Optimal Blood Pressure Targets.
AB - BP treatment thresholds/targets determine when to initiate treatment and to what
level BP should be reduced. The Seventh Joint National Committee on Prevention,
Detection, Evaluation, and Treatment of High Blood Pressure (JNC-7) recommended a
target of <140/90 for most patients and a target <130/80 mmHg for patients with
diabetes or chronic kidney disease. Subsequently, meta-analyses, retrospective
studies relating on-treatment BP to clinical outcomes and two large, randomized
clinical trials (RCTs) have re-evaluated BP targets. In Action to Control
Cardiovascular Risk in Diabetes (ACCORD), a systolic blood pressure (SBP) <120
mmHg was found not to be superior to SBP <140 mmHg in diabetics. In SPRINT
(Systolic Blood Pressure Intervention Trial) which studied a different
population, the lower target resulted in a 25% cardiovascular event reduction.
Despite unresolved issues, certain recommendations can be made with confidence.
SBP >160 mmHg should, with rare exceptions, be treated. The historical
threshold/target of 140/90 mmHg remains reasonable in most patients in
identifying "treatable" risk, i.e., risk high enough to justify treatment and for
which available treatment is effective enough to result in significant endpoint
reduction. Above 140/90 mmHg, most low-to-moderate risk people should be treated
and this target is also appropriate for the majority of high-risk individuals
with diabetes, CKD, and/or CAD. The advisability of initiating or intensifying
treatment with BPs in the 130s remains equivocal. The next steps in the search
for more precise BP targets should include (1) standardization of BP measurement
techniques and (2) well-designed RCTs evaluating a treatment target of SBP <130
in carefully categorized patient populations.
PMID- 28707235
TI - Adsorptive removal of five heavy metals from water using blast furnace slag and
fly ash.
AB - Heavy metals can be serious pollutants of natural water bodies causing health
risks to humans and aquatic organisms. The purpose of this study was to
investigate the removal of five heavy metals from water by adsorption onto an
iron industry blast furnace slag waste (point of zero charge (PZC) pH 6.0; main
constituents, Ca and Fe) and a coal industry fly ash waste (PZC 3.0; main
constituents, Si and Al). Batch study revealed that rising pH increased the
adsorption of all metals with an abrupt increase at pH 4.0-7.0. The Langmuir
adsorption maximum for fly ash at pH 6.5 was 3.4-5.1 mg/g with the adsorption
capacity for the metals being in the order Pb > Cu > Cd, Zn, Cr. The
corresponding values for furnace slag were 4.3 to 5.2 mg/g, and the order of
adsorption capacities was Pb, Cu, Cd > Cr > Zn. Fixed-bed column study on furnace
slag/sand mixture (1:1 w/w) revealed that the adsorption capacities were
generally less in the mixed metal system (1.1-2.1 mg/g) than in the single metal
system (3.4-3.5 mg/g). The data for both systems fitted well to the Thomas model,
with the adsorption capacity being the highest for Pb and Cu in the single metal
system and Pb and Cd in the mixed metal system. Our study showed that fly ash and
blast furnace slag are effective low-cost adsorbents for the simultaneous removal
of Pb, Cu, Cd, Cr and Zn from water.
PMID- 28707236
TI - Historical record of nutrients inputs into the Xin'an Reservoir and its potential
environmental implication.
AB - The Xin'an Reservoir is an important water supply source and water conservation
area for the Qiantang River. However, after the occurrence of the two algae
blooms in 1998 and 1999, the safety of water quality has been put into question.
In order to study the historical deposition of nutrients, sediment cores were
collected in different regions from the Xin'an Reservoir. The stable isotopes
delta13C and delta15N, nutrients, total organic carbon (TOC), and inorganic
carbon (IC) in the sediment cores were determined. Radiometric methods (210Pb and
137Cs) were used to obtain sediment chronologies. Spatially, it was found that
the average total nitrogen (TN) content in the upper 5 cm of sediments increased
from 0.21% in the riverine zone, to 0.33%, and then to 0.57% in the lacustrine
zone. The average TP content in the upper 5 cm increased from 0.67 g kg-1 in the
riverine zone, to 1.03 g kg-1 in the estuary region, and then to 1.65 g kg-1 in
the lacustrine zone. In addition, TOC levels showed a distinct increase from
1.42% in the bottom to 5.97% in the surface of the lacustrine zone. These results
demonstrated that although primary productivity and the input of nutrients
constantly increased in recent years, algae blooms rarely occurred in the Xin'an
Reservoir, due to "depth effect" and an aquatic environment protection-oriented
fishery policy. However, high TOC flux and high bio-available phosphorus and
nitrogen in surface sediment demonstrated that the reservoir is still confronted
with the potential risk of algae blooms.
PMID- 28707237
TI - Selenium protects against cadmium-induced kidney apoptosis in chickens by
activating the PI3K/AKT/Bcl-2 signaling pathway.
AB - Cadmium (Cd) is a toxic heavy metal that can induce apoptosis. Selenium (Se) is a
necessary trace element and can antagonize the toxicity of many heavy metals,
including Cd. PI3K/AKT/Bcl-2 is a key survival signaling pathway that regulates
cellular defense system against oxidative injury as well as cell proliferation,
survival, and apoptosis. The antagonistic effects of Se on Cd-induced toxicity
have been reported. However, little is known about the effect of Se on Cd-induced
apoptosis in chicken kidneys via the PI3K/AKT/Bcl-2 signaling pathway. In the
present study, we fed chickens with Se, Cd, or both Se and Cd supplements, and
after 90 days of treatment, we detected the related index. The results showed
that the activity of inducible nitric oxide synthase (iNOS) and concentration of
nitric oxide (NO) were increased; activities of the mitochondrial respiratory
chain complexes (complexes I, II, and V) and ATPases (the Na+-K+-ATPase, the Mg2+
ATPase, and the Ca2+-ATPase) were decreased; expression of PI3K, AKT, and Bcl-2
were decreased; and expression of Bax, Bak, P53, Caspase-3, Caspase-9, and
cytochrome c (Cyt c) were increased. Additionally, the results of the TUNEL assay
showed that the number of apoptotic cells was increased in the Cd group. By
contrast, there was a significant improvement of the correlation indicators and
occurrence of apoptosis in the Se + Cd group compared to the Cd group. In
conclusion, our results confirmed that Se had a positive effect on ameliorating
Cd-induced apoptosis in chicken kidney tissue by activating the PI3K/AKT/Bcl-2
signaling pathway.
PMID- 28707238
TI - Effects of air/fuel ratio on gas emissions in a small spark-ignited non-road
engine operating with different gasoline/ethanol blends.
AB - This study investigates the effects of several blends of gasoline and anhydrous
ethanol on exhaust emission concentrations of carbon monoxide (CO), total
hydrocarbons (HCs), and nitrogen oxides (NOx) from a small spark-ignited non-road
engine (SSINRE). Tests were carried out for different air/fuel equivalence ratios
as measured by lambda (lambda). A 196 cm3 single-cylinder four-stroke engine
generator operating at a constant load of 2.0 kW was used; pollutant gas
concentrations were measured with an automatic analyzer similar to those
typically used in vehicle inspections. The results showed that as the ethanol
content of the mixture increased the concentrations of CO, HCs, and NOx reduced
by 15, 53, and 34%, respectively, for values of lambda < 1 (rich mixture) and by
52, 31, and 16% for values of lambda > 1 (lean mixture). Overall, addition of
anhydrous ethanol to the gasoline helped to reduce emissions of the pollutant
gases investigated, what contributes to photochemical smog reduction and quality
of life in urban areas.
PMID- 28707239
TI - Microplastic pollution in deposited urban dust, Tehran metropolis, Iran.
AB - Environmental pollutants such as microplastics have become a major concern over
the last few decades. We investigated the presence, characteristics, and
potential health risks of microplastic dust ingestion. The plastic load of 88 to
605 microplastics per 30 g dry dust with a dominance of black and yellow granule
microplastics ranging in size from 250 to 500 MUm was determined in 10 street
dust samples using a binocular microscope. Fluorescence microscopy was found to
be ineffective for detecting and counting plastic debris. Scanning electron
microscopy, however, was useful for accurate detection of microplastic particles
of different sizes, colors, and shapes (e.g., fiber, spherule, hexagonal,
irregular polyhedron). Trace amounts of Al, Na, Ca, Mg, and Si, detected using
energy dispersive X-ray spectroscopy, revealed additives of plastic polymers or
adsorbed debris on microplastic surfaces. As a first step to estimate the adverse
health effects of microplastics in street dust, the frequency of microplastic
ingestion per day/year via ingestion of street dust was calculated. Considering
exposure during outdoor activities and workspaces with high abundant
microplastics as acute exposure, a mean of 3223 and 1063 microplastic particles
per year is ingested by children and adults, respectively. Consequently, street
dust is a potentially important source of microplastic contamination in the urban
environment and control measures are required.
PMID- 28707240
TI - Elemental mobility in sulfidic mine tailings reclaimed with paper mill by
products as sealing materials.
AB - Sealing layers made of two alkaline paper mill by-products, fly ash and green
liquor dregs, were placed on top of 50-year-old sulfide-containing tailings as a
full-scale remediation approach. The performance and effectiveness of the sealing
layers with high water content for an oxygen barrier and low hydraulic
conductivity for a sealing layer in preventing the formation of acid rock
drainage were evaluated 5 years after the remediation. The leaching behavior of
the covered tailings was studied using batch leaching tests (L/S ratio 10 L/kg).
The leaching results revealed that, in general, the dregs- and ash-covered
tailings released relatively lower concentrations of many elements contained in
acid rock drainage compared to those from the uncovered tailings. A change in the
chemical composition and mineralogical state of the tailings was observed for the
tailings beneath the covers. The increase in pH caused by the alkaline materials
promoted metal precipitation. Geochemical modeling using PHREEQC confirmed most
of the geochemical changes of the covered tailings. Both the ash and dregs showed
potential to function as sealing materials in terms of their geochemical
properties. However, mobilization of Zn and Ni from the lower part of the dregs
covered tailings was observed. The same phenomenon was observed for the lower
part of the ash-covered tailings. Ash showed advantages over dregs as a cover
material; based on geochemical studies, the ash immobilized more elements than
the dregs did. Lysimeters were installed below the sealing layers, and
infiltrating water chemistry and hydrology were studied to monitor the amount and
quality of the leachate percolating through.
PMID- 28707241
TI - An approach to study ultrastructural changes and adaptive strategies displayed by
Acinetobacter guillouiae SFC 500-1A under simultaneous Cr(VI) and phenol
treatment.
AB - Acinetobacter guillouiae SFC 500-1A, a native bacterial strain isolated from
tannery sediments, is able to simultaneously remove high concentrations of Cr(VI)
and phenol. In this complementary study, high-resolution microscopy techniques,
such as atomic force microscopy (AFM) and transmission electron microscopy (TEM),
were used to improve our understanding of some bacterial adaptive mechanisms that
enhance their ability to survive. AFM contributed in gaining insight into changes
in bacterial size and morphology. It allowed the unambiguous identification of
pollutant-induced cellular disturbances and the visualization of bacterial cells
with depth sensitivity. TEM analysis revealed that Cr(VI) produced changes mainly
at the intracellular level, whereas phenol produced alterations at the membrane
level. This strain tended to form more extensive biofilms after phenol treatment,
which was consistent with microscopy images and the production of
exopolysaccharides (EPSs). In addition, other exopolymeric substances (DNA,
proteins) significantly increased under Cr(VI) and phenol treatment. These
exopolymers are important for biofilm formation playing a key role in bacterial
aggregate stability, being especially useful for bioremediation of environmental
pollutants. This study yields the first direct evidences of a range of different
changes in A. guillouiae SFC 500-1A which seems to be adaptive strategies to
survive in stressful conditions.
PMID- 28707242
TI - Urea removal coupled with enhanced electricity generation in single-chambered
microbial fuel cells.
AB - High concentration of total ammonia nitrogen (TAN) in the form of urea is known
to inhibit the performance of many biological wastewater treatment processes.
Microbial fuel cells (MFCs) have great potential for TAN removal due to its
unique oxic/anoxic environment. In this study, we demonstrated that increased
urea (TAN) concentration up to 3940 mg/L did not inhibit power output of single
chambered MFCs, but enhanced power generation by 67% and improved coulombic
efficiency by 78% compared to those obtained at 80 mg/L of TAN. Over 80% of
nitrogen removal was achieved at TAN concentration of 2630 mg/L. The increased
nitrogen removal coupled with significantly enhanced coulombic efficiency, which
was observed for the first time, indicates the possibility of a new electricity
generation mechanism in MFCs: direct oxidation of ammonia for power generation.
This study also demonstrates the great potential of using one MFC reactor to
achieve simultaneous electricity generation and urea removal from wastewater.
PMID- 28707243
TI - Research trends and hotspots related to ammonia oxidation based on bibliometric
analysis.
AB - Ammonia oxidation is the rate-limiting and central step in global biogeochemistry
cycle of nitrogen. A bibliometric analysis based on 4314 articles extracted from
Science Citation Index Expanded database was carried out to provide insights into
publication performances and research trends of ammonia oxidation in the period
1991-2014. These articles were originated from a wide range of 602 journals and
95 Web of Science Categories, among which Applied and Environmental Microbiology
and Environmental Sciences took the leading position, respectively. Furthermore,
co-citation analysis conducted with help of CiteSpace software clearly
illustrated that ammonia-oxidizing bacteria (AOB), ammonia-oxidizing archaea
(AOA), and anaerobic ammonia oxidation (anammox) were three dominant research
themes. A total of 15 landmark works identified with the highest co-citation
frequencies at every 8 years were extracted, which demonstrated that the
establishments of culture-independent molecular biotechnologies as well as the
discoveries of anammox and AOA played the most significant roles in promoting the
evolution and development of ammonia oxidation research. Finally, word cluster
analysis further suggested that microbial abundance and community of AOA and AOB
was the most prominent hotspot, with soil and high-throughput sequencing as the
most promising ecosystem and molecular biotechnology. In addition, application of
anammox in nitrogen removal from wastewater has become another attractive
research hotspot. This study provides a basis for better understanding the
situations and prospective directions of the research field of ammonia oxidation.
PMID- 28707244
TI - Cytotoxic effects of seven Tunisian hospital wastewaters on the proliferation of
human breast cancer cell line MDA-231: correlation with their chemical
characterization.
AB - Hospital wastewaters contain large amounts of pharmaceutical residues, which may
eventually be discharged into the aquatic environment through wastewater
treatment plants, raising the question of their impact on human and environmental
health. This has prompted the launch of several monitoring studies into the most
commonly administered compounds in urban wastewater. The aim of this study was,
therefore, to explore the cytotoxic potential of wastewaters samples collected
from seven hospitals in Tunisia. The physicochemical analyses showed a large
fluctuation of certain parameters in the collected samples, such as chemical
oxygen demand (ranged from 860 to 1720 mg L-1), biochemical oxygen demand (ranged
from 385 to 747 mg L-1), total organic carbon (ranged from 256 to 562 g L-1),
total suspended solids (ranged from 905 to 1450 mg L-1), conductivity (ranged
from 3.31 to 7.14 MUsm/cm), and turbidity (ranged from 100 to 480 NTU). The
analysis using inductively coupled plasma mass spectrometry (ICP-MS) also showed
that hospital wastewater contains high concentrations of Hg (ranged from 0.0024
to 0.019 mg L-1). This could be explained by the variation of the activity and
the services in certain hospitals compared to others. All hospital wastewater
samples induced the proliferation of human breast cancer cell line MDA-231, even
at low concentrations (20 MUL/assay). Moreover, the maximum induction reached at
the concentration of 60 MUL/assay in wastewater samples from hospitals located in
Monastir, Sidi Bouzid, Mahdia, and Sfax with percentages of induction up to
42.33, 14, 7.61, and 5.42%, respectively. These observations could be due to the
presence of endocrine disrupting compounds (EDCs) in these wastewaters. Given
this, our results evidenced the potential risk of these hospital effluents to
environmental and public health.
PMID- 28707245
TI - Correlation of edge truncation with antibacterial activity of plate-like
anisotropic silver nanoparticles.
AB - The effect of silver nanoparticle anisotropy on the antibacterial properties has
been studied against Escherichia coli, Staphylococcus aureus, Bacillus, Vibrio
cholerae, and Streptococcus pyogenes. Anisotropic silver nanoparticles have been
synthesized by solvothermal process. The UV-visible absorption, X-ray
diffraction, and TEM studies show the anisotropic nature of silver nanoparticles.
The results demonstrate that the anisotropic silver nanoparticles undergo a shape
dependent interaction with the bacteria, and the nanoparticles with higher
anisotropy exhibit the superior antibacterial activity. Silver nanoparticles with
sharp edges and corners displayed the stronger biocidal action, in comparison to
the anisotropic nanoparticles with round edges and corners. The sharpness of the
corners has been quantified using degree of truncation method. The variation in
degree of truncation and the antibacterial activity follows the same pattern.
PMID- 28707246
TI - Chemical characterization and receptor modeling of PM10 in the surroundings of
the opencast lignite mines of Western Macedonia, Greece.
AB - The Western Macedonian Lignite Center (WMLC) in northwestern Greece is the major
lignite center in the Balkans feeding four major power plants of total power
exceeding 4 GW. Concentrations of PM10 (i.e., particulate matters with diameters
<=10 MUm) are the main concern in the region, and the high levels observed are
often attributed to the activities related to power generation. In this study,
the contribution of fugitive dust emissions from the opencast lignite mines to
the ambient levels of PM10 in the surroundings was estimated by performing
chemical mass balance (CMB) receptor modeling. For this purpose, PM10 samples
were concurrently collected at four receptor sites located in the periphery of
the mine area during the cold and the warm periods of the year (November-December
2011 and August-September 2012), and analyzed for a total of 26 macro- and trace
elements and ionic species (sulfate, nitrate, chloride). The robotic chemical
mass balance (RCMB) model was employed for source identification/apportionment of
PM10 at each receptor site using as inputs the ambient concentrations and the
chemical profiles of various sources including the major mine operations, the fly
ash escaping the electrostatic filters of the power plants, and other primary and
secondary sources. Mean measured PM10 concentrations at the different sites
ranged from 38 to 72 MUg m-3. The estimated total contribution of mines ranged
between 9 and 22% in the cold period increasing to 36-42% in the dry warm period.
Other significant sources were vehicular traffic, biomass burning, and secondary
sulfate and nitrate aerosol. These results imply that more efficient measures to
prevent and suppress fugitive dust emissions from the mines are needed.
PMID- 28707247
TI - Reducing As availability in calcareous soils using nanoscale zero valent iron.
AB - Different methods, including the use of nanoscale zero-valent iron (NZVI), have
been used to treat arsenic (As)-contaminated environments, with much less data on
the use of NZVI in arsenic-calcareous-polluted soils. Accordingly, two different
experiments were conducted to investigate the effects of NZVI on the removal of
As from three different calcareous-polluted soils. In the first experiment, the
effects of soil type (differing in the rate of clay particles and organic carbon
including S1 (8.0 and 0.05%), S2 (20 and 0.2%), and S3 (20.5 and 0.8%)) and NZVI
concentration (0, 50, and 100 g kg-1 of dry soil) on the removal of As
extractable with distilled water were evaluated using a factorial design with
three replicates. In the second experiment, the NZVI concentrations were reduced
to 0, 2.5, 5.0, and 25 g kg-1, and the NZVI contact time (0.5, 48, 96, 192, 384,
and 768 h) was also tested. The analysis of variance in both experiments
indicated the significant effects (P < 0.01) of the experimental treatments on
the removal of As. The concentrations of available As in S3 (42.7 mg kg-1), S2
(20.22 mg kg-1), and S1 (24.22 mg kg-1) after using the 50 g kg-1 NZVI treatment
decreased to 0, 0, and 0.05 mg kg-1, respectively, which was not significantly
different from the 100 g kg-1 NZVI treatment. In the second experiment, using the
25 g kg-1 NZVI treatment, the concentration of available As significantly
decreased in S1 from 16.48 to 0.1767 mg kg-1, in S2 from 13.34 to 0.31 mg kg-1,
and in S3 from 33.67 to 0.84 mg kg-1. In the three soils, with increasing NZVI
concentration and contact time, the concentration of available As in the solution
phase significantly decreased (P = 0.01). S3, due to a higher rate of organic
matter, was less responsive to the NZVI treatments than the other soils. The
effectiveness of the nanoremediation method, tested in this research work, on the
stabilization of As in calcareous soils, is verified.
PMID- 28707248
TI - Macrophage M1 Plays a Positive Role in Aseptic Inflammation-Related Graft
Loosening After Anterior Cruciate Ligament Reconstruction Surgery.
AB - Macrophage-related inflammatory response is one of the main biological factors
resulting in failure of anterior cruciate ligament (ACL) reconstruction, although
the specific pathomechanism remains to be clarified. Our aim was to investigate
the association between graft loosening and macrophage-related inflammation in
cases of loosening of reconstructed ACL autografts. Tissue samples were obtained
from 21 patients who underwent a second-look arthroscopy within the first year
after arthroscopic ACL reconstruction using single-bundle hamstring tendon
autografts. Possible biological factors of graft loosening were analyzed using
polymerase chain reaction, Western blot, and hematoxylin/eosin and
immunohistochemical staining of graft tissue samples obtained during the second
look arthroscopy. Graft loosening was closely related to increased gene and
protein expression of inflammatory cytokines (TNF-alpha, IL-6, and IL-8) and
activation of the inflammation-related toll-like receptor (TLR) signaling (TLR2
and TLR4). The molecular expression of TGF-beta and type I and III collagen was
also inhibited to varying degrees, with decreased vascularization of the graft
due to an inhibition of VEGF. iNOS, a marker of M1 macrophage activation, was
highly expressed in cases of graft loosening, with no effect of M2 macrophages
identified. The activation of M1 macrophages and aseptic inflammation signaling
is an important biological factor of graft loosening after ACL reconstruction,
affecting ligamentization and the health of grafts.
PMID- 28707249
TI - QTL associated with resistance to cassava brown streak and cassava mosaic
diseases in a bi-parental cross of two Tanzanian farmer varieties, Namikonga and
Albert.
AB - KEY MESSAGE: QTL consistent across seasons were detected for resistance to
cassava brown streak disease induced root necrosis and foliar symptoms. The CMD2
locus was detected in an East African landrace, and comprised two QTL. Cassava
production in Africa is compromised by cassava brown streak disease (CBSD) and
cassava mosaic disease (CMD). To reduce costs and increase the precision of
resistance breeding, a QTL study was conducted to identify molecular markers
linked to resistance against these diseases. A bi-parental F1 mapping population
was developed from a cross between the Tanzanian farmer varieties, Namikonga and
Albert. A one-step genetic linkage map comprising 943 SNP markers and 18 linkage
groups spanning 1776.2 cM was generated. Phenotypic data from 240 F1 progeny were
obtained from two disease hotspots in Tanzania, over two successive seasons, 2013
and 2014. Two consistent QTLs linked to resistance to CBSD-induced root necrosis
were identified in Namikonga on chromosomes II (qCBSDRNFc2Nm) and XI
(qCBSDRNc11Nm) and a putative QTL on chromosome XVIII (qCBSDRNc18Nm).
qCBSDRNFc2Nm was identified at Naliendele in both seasons. The same QTL was also
associated with CBSD foliar resistance. qCBSDRNc11Nm was identified at Chambezi
in both seasons, and was characterized by three peaks, spanning a distance of 253
kb. Twenty-seven genes were identified within this region including two LRR
proteins and a signal recognition particle. In addition, two highly significant
CMD resistance QTL (qCMDc12.1A and qCMDc12.2A) were detected in Albert, on
chromosome 12. Both qCMDc12.1A and qCMDc12.2A lay within the range of markers
reported earlier, defining the CMD2 locus. This is the first time that two loci
have been identified within the CMD2 QTL, and in germplasm of apparent East
African origin. Additional QTLs with minor effects on CBSD and CMD resistance
were also identified.
PMID- 28707250
TI - Genomic prediction of starch content and chipping quality in tetraploid potato
using genotyping-by-sequencing.
AB - KEY MESSAGE: Genomic prediction models for starch content and chipping quality
show promising results, suggesting that genomic selection is a feasible breeding
strategy in tetraploid potato. Genomic selection uses genome-wide molecular
markers to predict performance of individuals and allows selections in the
absence of direct phenotyping. It is regarded as a useful tool to accelerate
genetic gain in breeding programs, and is becoming increasingly viable for crops
as genotyping costs continue to fall. In this study, we have generated genomic
prediction models for starch content and chipping quality in tetraploid potato to
facilitate varietal development. Chipping quality was evaluated as the colour of
a potato chip after frying following cold induced sweetening. We used genotyping
by-sequencing to genotype 762 offspring, derived from a population generated from
biparental crosses of 18 tetraploid parents. Additionally, 74 breeding clones
were genotyped, representing a test panel for model validation. We generated
genomic prediction models from 171,859 single-nucleotide polymorphisms to
calculate genomic estimated breeding values. Cross-validated prediction
correlations of 0.56 and 0.73 were obtained within the training population for
starch content and chipping quality, respectively, while correlations were lower
when predicting performance in the test panel, at 0.30-0.31 and 0.42-0.43,
respectively. Predictions in the test panel were slightly improved when including
representatives from the test panel in the training population but worsened when
preceded by marker selection. Our results suggest that genomic prediction is
feasible, however, the extremely high allelic diversity of tetraploid potato
necessitates large training populations to efficiently capture the genetic
diversity of elite potato germplasm and enable accurate prediction across the
entire spectrum of elite potatoes. Nonetheless, our results demonstrate that GS
is a promising breeding strategy for tetraploid potato.
PMID- 28707251
TI - Benchmarking semiempirical and DFT methods for the interaction of thiophene and
diethyl sulfide molecules with a Ti(OH)4(H2O) cluster.
AB - Semiempirical methods pm6 and pm7 as well as density functional theory
functionals exchange LSDA, exchange-correlation PW91 and PBE, hybrid B3LYP1 and
PBE0 were compared for energy and geometry of thiophene, diethyl sulfide (DES)
molecules and their binding to a frozen Ti(OH)4(H2O) complex having one
coordinatively unsaturated Ti5C site representing small fragment of TiO2 anatase
(001) surface. PBE0/6-31G(d) with DFT-D3 dispersion correction was the best
method for description of thiophene and DES molecules geometries as comparison
with experimental data demonstrated. Semiempirical methods pm6 and pm7 resulted
in only three of four possible binding configurations of thiophene with the
Ti(OH)4(H2O) complex while pm7 described correctly the enthalpy and all
configurations of DES binding with the Ti(OH)4(H2O) complex. SBKJC
pseudopotential and LSDA with and without dispersion correction produced flawed
results for many configurations. PBE0 and PBE with and without dispersion
correction and PW91 with 6-31G(d) basis set systematically produced dependable
results for thiophene and DES binding to the Ti(OH)4(H2O) complex. PBE0-D3/6
31G(d), B3LYP1-D3/6-31G(d), and PBE-D3/6-31G(d) gave best match of binding energy
for thiophene while PBE0/6-31G(d) gave best match of DES binding energy as
comparison with CCSD(T) energy demonstrated. On the basis of the superior results
obtained with PBE0/6-31G(d), it is the recommended method for modeling of
adsorption over TiO2 surfaces. Such a conclusion is in agreement with recent
literature.
PMID- 28707252
TI - Spontaneous involution of a sinus pericranii.
PMID- 28707253
TI - The impact of forest roads on understory plant diversity in temperate hornbeam
beech forests of Northern Iran.
AB - Forest roads alter the biotic and abiotic components of ecosystems, modifying
temperature, humidity, wind speed, and light availability that, in turn, cause
changes in plant community composition and diversity. We aim at investigating and
comparing the diversity of herbaceous species along main and secondary forest
roads in a temperate-managed hornbeam-beech forest, north of Iran. Sixteen
transects along main and secondary forest roads were established (eight transects
along main roads and eight along secondary roads). To eliminate the effect of
forest type, all transects were located in Carpinetum-Fagetum forests, the
dominant forest type in the study area. The total length of each transect was 200
m (100 m toward up slope and 100 m toward down slope), and plots were established
along it at different distances from road edge. The diversity of herbaceous plant
species was calculated in each plot using Shannon-Wiener index, species richness,
and Pielou's index. The results showed that diversity index decreased when
distance from road edge increases. This decreasing trend continued up to 60 m
from forest road margin, and after this threshold, the index slightly increased.
Depending on the type of road (main or secondary) as well as cut or fill slopes,
the area showing a statistical different plant composition and diversity measured
through Shannon-Wiener, species richness, and Pielou's index is up to 10 m. The
length depth of the road edge effect found in main and secondary forest roads was
small, but it could have cumulative effects on forest microclimate and forest
associated biota at the island scale. Forest managers should account for the
effect of road buildings on plant communities.
PMID- 28707254
TI - Effect of oil palm on the Plecoptera and Trichoptera (Insecta) assemblages in
streams of eastern Amazon.
AB - The production of oil palm is expected to increase in the Amazon region. However,
expansion of oil palm plantation leads to significant changes in the physical
structure of aquatic ecosystems, mainly through the reduction of riparian
vegetation that is essential for aquatic biodiversity. Here, we evaluated the
effects of oil palm on the physical habitat structure of Amazonian stream
environments and assemblages of Plecoptera and Trichoptera (PT), both found in
these streams. We compared streams sampled in oil palm plantations (n = 13) with
natural forest areas ("reference" streams, n = 8), located in the eastern Amazon,
Brazil. Our results showed that oil palm streams were more likely to be in close
proximity to roads, had higher pH values, and higher amounts of fine substrate
deposited in the channel than reference streams. Further, these environmental
changes had important effects on the aquatic invertebrate assemblages, reducing
the abundance and richness of PT. Nevertheless, the genera composition of the
assemblages did not differ between reference and oil palm (PERMANOVA, pseudo-F
(1,19) = 1.891; p = 0.111). We conclude that oil palm production has clear
negative impacts on aquatic environments and PT assemblages in Amazonian streams.
We recommend that oil palm producers invest more in planning of road networks to
avoid the construction of roads near to the riparian vegetation. This planning
can minimize impacts of oil palm production on aquatic systems in the Amazon.
PMID- 28707255
TI - Comparative clinical study of Whitestar Signature phacoemulsification system with
standard and Ellips FX handpieces.
AB - PURPOSE: To compare the intraoperative parameters and postoperative outcomes
using two different phaco handpieces with different energy delivery systems of
the same phacoemulsification machine. METHODS: One hundred and sixty eyes of 160
cataract patients were randomly assigned to 2.40 mm phacoemulsification using the
AMO WhiteStar Signature(r) phaco system with the standard phaco handpiece (Group
1) or the Ellips FX phaco handpiece (Group 2). According to the lens opacities
classification system III, each group was divided into four subgroups of 20
patients each. U/S total time (UST), total phaco time (TPT), mean effective phaco
time, cumulative dissipated energy (CDE) and balanced salt solution (BSS)
consumption were studied. Visual acuity, corneal endothelium cell count and
corneal pachymetry were evaluated before surgery and 1, 7 and 30 days after
surgery. RESULTS: No statistically significant difference in terms of visual
acuity was observed between the two groups. The postoperative endothelial cell
loss and corneal pachymetry were similar between the two groups. In higher
density cataracts, Ellips FX showed the lower CDE and the lowest UST. TPT and BSS
consumption were significantly lower in the Ellips FX handpiece group.
CONCLUSIONS: The two phaco handpieces appeared to be safe. AMO Ellips FX
handpiece showed better performances and may be safer in lens removal, especially
in hard cataract patients.
PMID- 28707256
TI - Monitoring In-Vivo the Mammary Gland Microstructure during Morphogenesis from
Lactation to Post-Weaning Using Diffusion Tensor MRI.
AB - Lactation and the return to the pre-conception state during post-weaning are
regulated by hormonal induced processes that modify the microstructure of the
mammary gland, leading to changes in the features of the ductal / glandular
tissue, the stroma and the fat tissue. These changes create a challenge in the
radiological workup of breast disorder during lactation and early post-weaning.
Here we present non-invasive MRI protocols designed to record in vivo high
spatial resolution, T2-weighted images and diffusion tensor images of the entire
mammary gland. Advanced imaging processing tools enabled tracking the changes in
the anatomical and microstructural features of the mammary gland from the time of
lactation to post-weaning. Specifically, by using diffusion tensor imaging (DTI)
it was possible to quantitatively distinguish between the ductal / glandular
tissue distention during lactation and the post-weaning involution. The
application of the T2-weighted imaging and DTI is completely safe, non-invasive
and uses intrinsic contrast based on differences in transverse relaxation rates
and water diffusion rates in various directions, respectively. This study
provides a basis for further in-vivo monitoring of changes during the mammary
developmental stages, as well as identifying changes due to malignant
transformation in patients with pregnancy associated breast cancer (PABC).
PMID- 28707257
TI - Evaluation of Patient Satisfaction in a State Reference Center of Bipolar
Disorder.
PMID- 28707258
TI - "Connecting the Dots": A Qualitative Study of Home Health Nurse Perspectives on
Coordinating Care for Recently Discharged Patients.
AB - BACKGROUND: In 2012, nearly one-third of adults 65 years or older with Medicare
discharged to home after hospitalization were referred for home health care (HHC)
services. Care coordination between the hospital and HHC is frequently inadequate
and may contribute to medication errors and readmissions. Insights from HHC
nurses could inform improvements to care coordination. OBJECTIVE: To describe HHC
nurse perspectives about challenges and solutions to coordinating care for
recently discharged patients. DESIGN/PARTICIPANTS: We conducted a descriptive
qualitative study with six focus groups of HHC nurses and staff (n = 56)
recruited from six agencies in Colorado. Focus groups were recorded, transcribed,
and analyzed using a mixed deductive/inductive approach to theme analysis with a
team-based iterative method. KEY RESULTS: HHC nurses described challenges and
solutions within domains of Accountability, Communication, Assessing Needs &
Goals, and Medication Management. One additional domain of Safety, for both
patients and HHC nurses, emerged from the analysis. Within each domain, solutions
for improving care coordination included the following: 1) Accountability
hospital physicians willing to manage HHC orders until primary care follow-up,
potential legislation allowing physician assistants and nurse practitioners to
write HHC orders; 2) Communication-enhanced access to hospital records and direct
telephone lines for HHC; 3) Assessing Needs & Goals-liaisons from HHC agencies
meeting with patients in hospital; 4) Medication Management-HHC coordinating
directly with clinician or pharmacist to resolve discrepancies; and 5) Safety-HHC
nurses contributing non-reimbursable services for patients, and ensuring that
cognitive and behavioral health information is shared with HHC. CONCLUSIONS: In
an era of shared accountability for patient outcomes across settings, solutions
for improving care coordination with HHC are needed. Efforts to improve care
coordination with HHC should focus on clearly defining accountability for orders,
enhanced communication, improved alignment of expectations for HHC between
clinicians and patients, a focus on reducing medication discrepancies, and
prioritizing safety for both patients and HHC nurses.
PMID- 28707259
TI - Rhabdomyolysis and AKI with Atorvastatin and Sitagliptin Use in the Setting of
Low 25-Hydroxyvitamin D Levels.
AB - We report a case of an 86-year-old woman admitted to the hospital with
rhabdomyolysis and acute kidney injury 3 weeks after starting sitagliptin while
on long-term atorvastatin therapy. She also had low levels of 25-hydroxyvitamin D
and mild chronic kidney disease, which may have contributed to the development of
rhabdomyolysis. A review of the literature reveals four previous reports of this
drug interaction in elderly patients, some with underlying kidney disease.
PMID- 28707260
TI - Historical effects of dissolved organic carbon export and land management
decisions on the watershed-scale forest carbon budget of a coastal British
Columbia Douglas-fir-dominated landscape.
AB - BACKGROUND: To address how natural disturbance, forest harvest, and deforestation
from reservoir creation affect landscape-level carbon (C) budgets, a
retrospective C budget for the 8500 ha Sooke Lake Watershed (SLW) from 1911 to
2012 was developed using historical spatial inventory and disturbance data. To
simulate forest C dynamics, data was input into a spatially-explicit version of
the Carbon Budget Model-Canadian Forest Sector (CBM-CFS3). Transfers of
terrestrial C to inland aquatic environments need to be considered to better
capture the watershed scale C balance. Using dissolved organic C (DOC) and stream
flow measurements from three SLW catchments, DOC load into the reservoir was
derived for a 17-year period. C stocks and stock changes between a baseline and
two alternative management scenarios were compared to understand the relative
impact of successive reservoir expansions and sustained harvest activity over the
100-year period. RESULTS: Dissolved organic C flux for the three catchments
ranged from 0.017 to 0.057 Mg C ha-1 year-1. Constraining CBM-CFS3 to observed
DOC loads required parameterization of humified soil C losses of 2.5, 5.5, and
6.5%. Scaled to the watershed and assuming none of the exported terrestrial DOC
was respired to CO2, we hypothesize that over 100 years up to 30,657 Mg C may
have been available for sequestration in sediment. By 2012, deforestation due to
reservoir creation/expansion resulted in the watershed forest lands sequestering
14 Mg C ha-1 less than without reservoir expansion. Sustained harvest activity
had a substantially greater impact, reducing forest C stores by 93 Mg C ha-1 by
2012. However approximately half of the C exported as merchantable wood during
logging (~176,000 Mg C) may remain in harvested wood products, reducing the
cumulative impact of forestry activity from 93 to 71 Mg C ha-1. CONCLUSIONS:
Dissolved organic C flux from temperate forest ecosystems is a small but
persistent C flux which may have long term implications for C storage in inland
aquatic systems. This is a first step integrating fluvial transport of C into a
forest carbon model by parameterizing DOC flux from soil C pools. While
deforestation related to successive reservoir expansions did impact the watershed
scale C budget, over multi-decadal time periods, sustained harvest activity was
more influential.
PMID- 28707262
TI - Exercise N-13 cardiac positron emission tomography myocardial perfusion imaging
detecting ischemia in an adult patient with anomalous aortic origin of the left
main coronary artery from the right coronary sinus.
AB - Anomalous aortic origin of a coronary artery is a rare congenital condition that
has variable presentations from atypical chest pain to syncope and cardiac
arrest. Commonly used myocardial perfusion imaging techniques, stress agents, and
perfusion agents may have limited ability to detect inducible ischemia in this
rare patient group. We herein describe a unique case of anomalous left main
coronary artery from a common right coronary sinus ostium with a subpulmonic and
intramyocardial course. This patient had multiple atypical chest pain
presentations and multiple-negative pharmacologic single-photon emission-computed
tomography stress tests performed. Significant ischemia was detected via N-13
exercise cardiac positron emission tomography and with surgical intervention she
had resolution of her symptoms.
PMID- 28707261
TI - From Inflammation to Fibrosis-Molecular and Cellular Mechanisms of Myocardial
Tissue Remodelling and Perspectives on Differential Treatment Opportunities.
AB - PURPOSE OF REVIEW: In this review, we highlight the most important cellular and
molecular mechanisms that contribute to cardiac inflammation and fibrosis. We
also discuss the interplay between inflammation and fibrosis in various
precursors of heart failure (HF) and how such mechanisms can contribute to
myocardial tissue remodelling and development of HF. RECENT FINDINGS: Recently,
many research articles attempt to elucidate different aspects of the interplay
between inflammation and fibrosis. Cardiac inflammation and fibrosis are major
pathophysiological mechanisms operating in the failing heart, regardless of HF
aetiology. Currently, novel therapeutic options are available or are being
developed to treat HF and these are discussed in this review. A progressive
disease needs an aggressive management; however, existing therapies against HF
are insufficient. There is a dynamic interplay between inflammation and fibrosis
in various precursors of HF such as myocardial infarction (MI), myocarditis and
hypertension, and also in HF itself. There is an urgent need to identify novel
therapeutic targets and develop advanced therapeutic strategies to combat the
syndrome of HF. Understanding and describing the elements of the inflammatory and
fibrotic pathways are essential, and specific drugs that target these pathways
need to be evaluated.
PMID- 28707263
TI - Delivery of viral vectors for gene therapy in intimal hyperplasia and restenosis
in atherosclerotic swine.
AB - Cardiovascular diseases including atherosclerosis are a major financial and
health burden globally. Inflammation associated with atherosclerosis results in
the development of plaques that can rupture causing thrombosis, stroke, or death.
The most widely used treatment for the removal of atherosclerotic plaques is
percutaneous transluminal coronary angioplasty (PTCA) with or without stenting.
Although this is a safer and minimally invasive method, restenosis and intimal
hyperplasia after interventional procedure remains a major hurdle and more
refined approaches are needed. Studies in large animal models such as pigs have
facilitated a greater understanding of the underlying mechanisms of the disease
and provided novel targets for therapeutic intervention. In pre-clinical studies,
viral vector gene therapy has emerged as a promising option for the reduction
and/or prevention of restenosis and intimal hyperplasia. Although studies in
animal models have generated promising results, clinical trials have yet to prove
the clinical efficacy of gene therapy in coronary artery diseases. In this
review, we examined and critically reviewed the most recent advances in viral
vector gene therapy obtained from studies using porcine model of atherosclerosis.
PMID- 28707264
TI - Evaluation of propylene glycol nanoliposomes containing curcumin on burn wound
model in rat: biocompatibility, wound healing, and anti-bacterial effects.
AB - Curcumin is an effective wound healing agent in burn therapy, but due to its low
bioavailability, it is required to be formulated for topical therapy. Liposomal
nanocarriers are developed as stable and efficient dermal delivery systems. In
this study, we prepared curcumin-propylene glycol liposomes (Cur-PgL) to treat
animals subjected to second degree burns. The characterization tests confirmed
the production of monodisperse nanoliposomes of average size of about 145 nm with
high entrapment efficiency percentage and a sustained release behavior. TEM
analysis of nanocarriers showed no aggregation in long time storage up to 60
days. The biocompatibility of the Cur-PgL formulation was evaluated by ISO
standards. We found that Cur-PgL 0.3% was the effective dose in injured rats
without any side effects on intact skin. The cytotoxicity of the Cur-PgL 0.3%
nanovesicles was also assessed on human dermal fibroblast (HDF) cells. The
results showed no detectable cytotoxicity, but considerable cytotoxicity was
observed in higher concentration of 1.5 and 3 mg/ml of free and PgL forms of
curcumin. Eight days of application of Cur-PgL on burned rats resulted in a
significant (P<0.001) recovery of wound repair parameters, and after 18 days,
wound contraction occurred significantly (P < 0.001) compared to the other
groups. The antibacterial activity of the Cur-PgL formulation was found to be
similar to the silver sulfadiazine (SSD) cream 1% regarding the inhibition of the
bacterial growth. In conclusion, the low dose of curcumin nanoliposomal
formulation efficiently improved injuries and infections of burn wounds and it
can be considered in burn therapy.
PMID- 28707265
TI - Editorial.
PMID- 28707266
TI - 6-OHDA-Lesioned Adult Zebrafish as a Useful Parkinson's Disease Model for
Dopaminergic Neuroregeneration.
AB - Conventional mammalian models of neurodegeneration are often limited by futile
axonogenesis with minimal functional recuperation of severed neurons. The
emergence of zebrafish, a non-mammalian model with excellent neuroregenerative
properties, may address these limitations. This study aimed to establish an adult
zebrafish-based, neurotoxin-induced Parkinson's disease (PD) model and
subsequently validate the regenerative capability of dopaminergic neurons (DpN).
The DpN of adult male zebrafish (Danio rerio) were lesioned by microinjecting 6
hydroxydopamine (6-OHDA) neurotoxin (6.25, 12.5, 18.75, 25, 37.5, 50 and 100
mg/kg) into the ventral diencephalon (Dn). This was facilitated by an optimised
protocol that utilised 1,1'-dioctadecyl-3,3,3',3'-tetramethyl
indocarbocyanineperchlorate (DiI) dye to precisely identify the injection site.
Immunostaining was utilised to identify the number of tyrosine hydroxylase
immunoreactive (TH-ir) DpN in brain regions of interest (i.e. olfactory bulb,
telencephalon, preoptic area, posterior tuberculum and hypothalamus). Open tank
video recordings were performed for locomotor studies. The Dn was accessed by
setting the injection angle of the microinjection capillary to 60 degrees and
injection depth to 1200 MUm (from the exposed brain surface). 6-OHDA (25 mg/kg)
successfully ablated >85% of the Dn DpN (preoptic area, posterior tuberculum and
hypothalamus) whilst maintaining a 100% survival. Locomotor analysis of 5-min
recordings revealed that 6-OHDA-lesioned adult zebrafish were significantly (p <
0.0001) reduced in speed (cm/s) and distance travelled (cm). Lesioned zebrafish
showed full recovery of Dn DpN 30 days post-lesion. This study had successfully
developed a stable 6-OHDA-induced PD zebrafish model using a straightforward and
reproducible approach. Thus, this developed teleost model poses exceptional
potentials to study DpN regeneration.
PMID- 28707267
TI - "As a Community, We Need to be More Health Conscious": Pastors' Perceptions on
the Health Status of the Black Church and African-American Communities.
AB - BACKGROUND: Churches are recognized for their potential capacity to provide
health services and interventions to address health disparities in African
Americans (blacks). Since pastors are central community leaders, their support
and involvement can influence both implementation and outcomes for church-based
health programs. The purpose of this qualitative study was to explore pastors'
perceptions of congregant health status within the black church. METHODS: Semi
structured interviews were conducted with 11 pastors whose female congregants
participated in a physical activity intervention. Thematic analysis techniques
were used to analyze interview data. RESULTS: Three major themes emerged: (1)
health risks in the African-American community, (2) health promotion in the black
church, and (3) the importance of women in the black family and the church.
Pastors noted numerous health disparities affecting their congregants and the
African-American community at large, including obesity and infant mortality. They
viewed health holistically and included faith in their perspectives. According to
pastors, holistic health was promoted through health ministry programming in
black churches. Women were described as the cornerstone of the black church, yet
faced unique health concerns from their roles as family caretakers and
congregants. DISCUSSION: Pastors shared their major concerns for congregant
health status and the African-American community. Health interventions focusing
on African-Americans in church settings should include pastor involvement and
should incorporate holistic approaches to address health risks.
PMID- 28707268
TI - 'Hey, We Are the Best Ones at Dealing with Our Own': Embedding a Culturally
Competent Program for Maori and Pacific Island Children into a Mainstream Health
Service in Queensland, Australia.
AB - OBJECTIVE: We present the results of one component of an external evaluation of
Good Start Program (GSP), a community-based program for the prevention of chronic
disease among Maori and Pacific Island (MPI) communities living in the state of
Queensland, Australia. DESIGN: An evaluation of the GSP was undertaken using a
mixed methods approach. This paper reports on the qualitative component where
interview and focus group data was collected, using Talanoa, a culturally
tailored research methodology. Respondents included school students, community
groups, teachers and parents, as well as the Good Start implementation team.
RESULT(S): The five broad themes that emerged from this evaluation related to (i)
components of cultural-competence and (ii) perceived impact of the program. The
views of all participants reinforced the importance of culturally appropriate
programs and highlighted how the multicultural health workers (MHWs) contributed
to the program's perceived success. The challenges in understanding restrictions
of the mainstream health service framework were noted indicating the need for it
to be flexible in incorporating culturally appropriate components if a program
was to be embraced. CONCLUSION: The qualitative evaluation of the GSP suggests
that culturally tailored programs, delivered by MHWs, have the potential to
impact positively on community-level behavioural changes that improve health.
These findings, supported by studies from other countries, contribute to the
evidence that cultural-tailoring of programs is critical for ensuring that
culturally appropriate initiatives are embedded in health care systems that
support multicultural communities. Embedding includes the development of
culturally appropriate policies, a culturally competent workforce and long-term
funding to support culturally competent initiatives.
PMID- 28707269
TI - Complete genomic sequence of common reed chlorotic stripe virus, a novel member
of the family Potyviridae.
AB - Common reed (Phragmites australis) plants showing chlorotic stripe symptoms on
leaves were found in Gansu Province, China. Deep sequencing of small RNAs from
symptomatic leaves identified a putative potyvirus, which was named common reed
chlorotic stripe virus (CRCSV). The full genome sequence was determined by
reverse transcription PCR, rapid amplification of cDNA ends (RACE) PCR, and
sequencing. It consists of 9,426 nucleotides, excluding the poly(A) tail, and
contains a large open reading frame encoding a polyprotein of 3,014 amino acids.
Putative proteolytic cleavage sites were identified. Since CRCSV shared low
sequence similarity (35%-37% identity) to any known members of the family
Potyviridae and it clustered uniquely in phylogenetic analysis of either the
polyprotein or the coat protein, CRCSV is a distinct, previously undescribed
member of the family Potyviridae.
PMID- 28707270
TI - Profiling of cellular microRNA responses during the early stages of KSHV
infection.
AB - Kaposi's sarcoma-associated herpesvirus (KSHV) causes a variety of cancers,
including Kaposi's sarcoma (KS), primary effusion lymphoma (PEL), and
multicentric Castleman disease (MCD). Host cellular microRNAs (miRNAs) play
important post-transcriptional regulatory roles in gene expression and can
greatly influence virus-host cell interactions. This study investigated cellular
miRNA expression profiles operating in response to early stages of KSHV infection
of human Burkitt lymphoma B cells (BJAB). We employed deep sequencing to analyze
miRNA expression in KSHV-infected BJAB cells 15 min post infection (PI) and
compared this to uninfected BJAB cells. A total of 32 known miRNAs and 28 novel
miRNA candidates were differentially expressed in KSHV-infected compared to
uninfected BJAB cells. Interestingly, miRNA expression profiles during the early
stages of viral infection yielded comparable results when UV-inactivated KSHV was
used. The deep sequencing results were further confirmed by performing real-time
reverse transcription PCR. The target genes predicted to be regulated by both the
known and novel miRNAs are mainly involved in assisting virus entry, inducing
critical cell signaling, initiating transcription of immediate early genes,
promoting latent infection, and modulating the host immune response. For the
first time, we provide insight into the host cellular miRNA expression profiles
in response to early stages of KSHV infection of human B cells. Furthermore, this
study offers a valuable basis for further investigation on the roles of cellular
miRNAs in the KSHV entry process.
PMID- 28707271
TI - Identification and genetic characterization of a novel circular single-stranded
DNA virus in a human upper respiratory tract sample.
AB - Metagenomic analysis through high-throughput sequencing is a tool for detecting
both known and novel viruses. Using this technique, a novel circular single
stranded DNA (ssDNA) virus genome was discovered in respiratory secretions from a
febrile traveler. The virus, named human respiratory-associated PSCV-5-like virus
(HRAPLV), has a genome comprising 3,018 bases, with two major putative ORFs
inversely encoding capsid (Cap) and replicase (Rep) protein and separated by two
intergenic regions. One stem-loop structure was predicted in the larger
intergenic region (LIR). The predicted amino acid sequences of the Cap and Rep
proteins of HRAPLV showed highest identity to those of porcine stool-associated
circular virus 5 isolate CP3 (PoSCV 5) (53.0% and 48.9%, respectively). The host
tropism of the virus is unknown, and further study is warranted to determine
whether this novel virus is associated with human disease.
PMID- 28707272
TI - First molecular characterization of canine parvovirus strains in Sardinia, Italy.
AB - Canine parvovirus type 2 (CPV-2) is responsible of acute hemorrhagic
gastroenteritis in young dogs. CPV-2 emerged in 1978 in the USA, but new
antigenic types, CPV-2a, 2b and 2c, have completely replaced the original type.
In this study, we analyzed 81 animals collected in Sardinia, Italy. The VP2
sequence analysis of 27 positive samples showed that all antigenic CPV-2 types
are circulating. CPV-2b seems to be the most widespread variant, followed by CPV
2a. Furthermore, 12 CPV-2b strains displayed further amino acid substitutions and
formed a separate cluster in a phylogenetic tree, indicating regional genetic
variation.
PMID- 28707273
TI - Team communication patterns in emergency resuscitation: a mixed methods
qualitative analysis.
AB - BACKGROUND: In order to enhance patient safety during resuscitation of critically
ill patients, we need to optimize team communication and enhance team situational
awareness but little is known about resuscitation team communication patterns.
The objective of this study is to understand how teams communicate during
resuscitation; specifically to assess for a shared mental model (organized
understanding of a team's relationships) and information needs. METHODS: We
triangulated 3 methods to evaluate resuscitation team communication at a tertiary
care academic trauma center: (1) interviews; (2) simulated resuscitation
observations; (3) live resuscitation observations. We interviewed 18
resuscitation team members about shared mental models, roles and goals of team
members and procedural expectations. We observed 30 simulated resuscitation video
recordings and documented the timing, source and destination of communication and
the information category. We observed 12 live resuscitations in the emergency
department and recorded baseline characteristics of the type of resuscitations,
nature of teams present and type and content of information exchanges. The data
were analyzed using a qualitative communication analysis method. RESULTS: We
found that resuscitation team members described a shared mental model.
Respondents understood the roles and goals of each team member in order to
provide rapid, efficient and life-saving care with an overall need for
situational awareness. The information flow described in the interviews was
reflected during the simulated and live resuscitations with the most responsible
physician and charting nurse being central to team communication. We consolidated
communicated information into six categories: (1) time; (2) patient status; (3)
patient history; (4) interventions; (5) assistance and consultations; 6) team
members present. CONCLUSIONS: Resuscitation team members expressed a shared
mental model and prioritized situational awareness. Our findings support a need
for cognitive aids to enhance team communication during resuscitations.
PMID- 28707275
TI - Vanilla (Vanilla planifolia Jacks.) cell suspension cultures: establishment,
characterization, and applications.
AB - The establishment and characterization of cell suspension cultures are an in
vitro culture technique very useful for various plant biotechnological
applications (production of secondary metabolites, mass micropropagation,
protoplast isolation and fusion, gene transfer and the investigation of cell
pathways). The objective of this study was to establish and characterization of
cell suspension cultures of V. planifolia by inducing friable calluses. For that,
friable calluses were obtained from immature seeds cultivated in MS medium
supplemented with 0.45 uM thidiazuron (TDZ). The effect of benzyladenine (BA) in
different concentrations was evaluated. Cultures were incubated under photoperiod
at continuous stirring at 120 rpm on an orbital shaker. The optimal condition
found for biomass growth in suspension cultures was 0.5 g of inoculum density
(fresh weight) in MS liquid, supplemented with 8.88 uM BA. The growth kinetics of
the cell suspension culture revealed a maximum cell growth (exponential growth
phase) at day 16 and an 80% cell viability. The establishment and
characterization of cell suspension cultures of V. planifolia constitute the
bases of future studies and above all a better biotechnological use of this crop.
PMID- 28707274
TI - Cancer Immunotherapies: Are They as Effective in the Elderly?
AB - Almost two-thirds of all new cancer diagnoses are made in persons over the age of
65 years, yet it is unclear if age affects patient responsiveness to
immunotherapy, which is increasingly becoming first-line therapy in advanced
stages of different tumor types. Preclinical animal studies may be difficult to
translate into humans since they frequently use young mice (2-3 months of age)
equivalent to adolescent human subjects. Nevertheless, ex vivo studies from
humans are concordant with mice tissue findings-older patients have an increased
density of circulating regulatory immune cells and a decreased ratio of naive-to
memory T cells. A review of different immunotherapy trials reveals that contrary
to expectations, advanced age generally does not hinder safety and clinical
response to different treatment modalities. A growing number of immune checkpoint
inhibitor immunotherapy trials have been published with basic safety and clinical
response data stratified by age. We present the clinical response data from 21
phase II/III clinical trials based on age stratification into young and old
subgroups. Data from these trials indicate that these agents have an overall low
toxicity profile and that they are similarly well-tolerated in young and old
patient subgroups. However, drug-specific differences exist for immune checkpoint
inhibition in elderly subjects when comparing overall survival and progression
free survival hazard ratios with those of young subjects. Additional work is
needed to better stratify 'responders' and 'nonresponders' within the elderly age
group in order to optimize immunotherapy use in a heterogeneous patient
population.
PMID- 28707276
TI - Microalgal cultivation for value-added products: a critical enviro-economical
assessment.
AB - The present review focuses on the cultivation of algal biomass for generating
value-added products (VAP) and to assess their economic benefits and harmful
environmental impact. Additionally, the impact of bioreactor designs on the yield
of microalgal biomass for VAP is also considered. All these factors are discussed
in relation to the impact of microalgae production on the bio-economy sector of
commercial biotechnology.
PMID- 28707277
TI - Open-Label Allopregnanolone Treatment of Men with Fragile X-Associated
Tremor/Ataxia Syndrome.
AB - Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset
neurodegenerative disorder affecting approximately 45% of male and 16% of female
carriers of the FMR1 premutation over the age of 50 years. Currently, no
effective treatment is available. We performed an open-label intervention study
to assess whether allopregnanolone, a neurosteroid promoting regeneration and
repair, can improve clinical symptoms, brain activity, and magnetic resonance
imaging (MRI) measurements in patients with FXTAS. Six patients underwent weekly
intravenous infusions of allopregnanolone (2-6 mg over 30 min) for 12 weeks. All
patients completed baseline and follow-up studies, though MRI scans were not
collected from 1 patient because of MRI contraindications. The MRI scans from
previous visits, along with scans from 8 age-matched male controls, were also
included to establish patients' baseline condition as a reference. Functional
outcomes included quantitative measurements of tremor and ataxia and
neuropsychological evaluations. Brain activity consisted of event-related
potential N400 word repetition effect during a semantic memory processing task.
Structural MRI outcomes comprised volumes of the hippocampus, amygdala, and fluid
attenuated inversion recovery hyperintensities, and microstructural integrity of
the corpus callosum. The results of the study showed that allopregnanolone
infusions were well tolerated in all subjects. Before treatment, the patients
disclosed impairment in executive function, verbal fluency and learning, and
progressive deterioration of all MRI measurements. After treatment, the patients
demonstrated improvement in executive functioning, episodic memory and learning,
and increased N400 repetition effect amplitude. Although MRI changes were not
significant as a group, both improved and deteriorated MRI measurements occurred
in individual patients in contrast to uniform deterioration before the treatment.
Significant correlations between baseline MRI measurements and changes in
neuropsychological test scores indicated the effects of allopregnanolone on
improving executive function, learning, and memory for patients with relatively
preserved hippocampus and corpus callosum, while reducing psychological symptoms
for patients with small hippocampi and amygdalae. The findings show the promise
of allopregnanolone in improving cognitive functioning in patients with FXTAS and
in partially alleviating some aspects of neurodegeneration. Further studies are
needed to verify the efficacy of allopregnanolone for treating FXTAS.
PMID- 28707278
TI - Daclizumab: Development, Clinical Trials, and Practical Aspects of Use in
Multiple Sclerosis.
AB - Daclizumab is a humanized monoclonal antibody directed towards CD25, the alpha
subunit of the high-affinity interleukin (IL)-2 receptor. Daclizumab exerts its
effects via multiple mechanisms, including reduction of IL-2-mediated lymphocyte
activation and upregulation of CD56-bright natural killer cells. Intravenous
daclizumab (ZenapaxTM) was initially approved for prevention of rejection in
renal transplant. In subsequent early testing, followed by larger-scale phase II
and phase III trials, both intravenous and subcutaneous daclizumab have
demonstrated clinical efficacy in the treatment of multiple sclerosis. The
subcutaneous daclizumab prepared by high-yield process was utilized in the
advanced phase II and phase III trials (SELECT and DECIDE). High-yield process
daclizumab is now approved by the US Food and Drug Administration for relapsing
remitting multiple sclerosis, and is now formally termed daclizumab beta (DAC
beta; ZinbrytaTM). In this review, the early development of anti-IL-2 receptor
alpha monoclonal antibodies and the properties of IL-2 and its receptor are
discussed, and diverse mechanisms of action for daclizumab are presented. Results
of the CHOICE, SELECT, and DECIDE clinical trials are discussed in detail.
Adverse events observed in clinical trials included cutaneous reactions, liver
enzyme elevations, infections, and autoimmune phenomena. DAC-beta is a monthly,
patient-administered subcutaneous injection that requires enrollment in a safety
monitoring (REMS) program for monthly liver function testing. Prescribers should
be aware of the potential adverse events, as early recognition and management is
important, particularly in cutaneous and hepatic reactions. Continued clinical
experience with DAC-beta, including observations from the REMS program, will
define its place in the armamentarium of immunotherapeutics for relapsing
remitting multiple sclerosis.
PMID- 28707279
TI - Sarcolipin expression is repressed by endoplasmic reticulum stress in C2C12
myotubes.
AB - Sarcolipin is a transmembrane protein expressed in the sarco/endoplasmic
reticulum of skeletal and atrial muscles in large animals. Sarcolipin plays
crucial roles in heat production through modifying the function of
sarco/endoplasmic reticulum Ca2+ ATPase, thereby being involved in thermogenesis
and systemic metabolism. In skeletal muscle, endoplasmic reticulum (ER) stress
has been implicated in several conditions, such as insulin resistance, muscle
diseases, and hypo/hyper-contraction. Here, we investigated the effect of ER
stress on sarcolipin expression in skeletal muscle cells, C2C12 myotubes. First,
gene expression of sarcolipin was confirmed in the cells during myogenesis. Then,
ER stress was induced in C2C12 myotubes by treatment with tunicamycin or
thapsigargin. Sarcolipin messenger RNA (mRNA) and protein expression were
significantly reduced by ER stress induction. The reduction was independent of
inositol-requiring element 1 (IRE1), which is activated by ER stress and has
potent endonuclease activity, when evaluated by treatment with an IRE1 inhibitor,
4MU8C. On the other hand, sarcolipin mRNA stability was reduced under the ER
stress when evaluated by treatment with actinomycin D. In conclusion, these
results show that ER stress represses sarcolipin expression due to changes in
mRNA stability in C2C12 myotubes.
PMID- 28707280
TI - Multi-regulatory network of ROS: the interconnection of ROS, PGC-1 alpha, and
AMPK-SIRT1 during exercise.
AB - Transcriptional factors are easily susceptible to any stimuli, including
exercise. Exercise can significantly influence PGC-1 alpha and AMPK-SIRT1
pathway, as it is involved in the regulation of energy metabolism and
mitochondrial biogenesis. Exercise is a major energy deprivation process by which
many of transcription factors get tuned positively. However, how transcription
factors help to boost the antioxidant defense system at cellular level is
elusive. It is well known that physical exercise can induce reactive oxygen
species, but how these reactive oxygen species can help to regulate multiple
transcription factors during exercise is an important area to be discussed yet.
This review mainly focuses on interconnecting role of PGC-1 alpha and AMPK-SIRT1
pathway during exercise and how these proteins are getting tuned by reactive
oxygen species in exercise condition.
PMID- 28707281
TI - Towards a Comprehensive Conceptual Framework of Active Travel Behavior: a Review
and Synthesis of Published Frameworks.
AB - PURPOSE OF REVIEW: This paper reviews the use of conceptual frameworks in
research on active travel, such as walking and cycling. Generic framework
features and a wide range of contents are identified and synthesized into a
comprehensive framework of active travel behavior, as part of the Physical
Activity through Sustainable Transport Approaches project (PASTA). PASTA is a
European multinational, interdisciplinary research project on active travel and
health. RECENT FINDINGS: Along with an exponential growth in active travel
research, a growing number of conceptual frameworks has been published since the
early 2000s. Earlier frameworks are simpler and emphasize the distinction of
environmental vs. individual factors, while more recently several studies have
integrated travel behavior theories more thoroughly. Based on the reviewed
frameworks and various behavioral theories, we propose the comprehensive PASTA
conceptual framework of active travel behavior. We discuss how it can guide
future research, such as data collection, data analysis, and modeling of active
travel behavior, and present some examples from the PASTA project.
PMID- 28707282
TI - A system to identify inhibitors of mTOR signaling using high-resolution growth
analysis in Saccharomyces cerevisiae.
AB - The mechanistic target of rapamycin (mTOR) is a central regulator of growth and
proliferation and mTOR inhibition is a promising therapy for a variety of
diseases and disorders. Inhibition of mTOR complex I (mTORC1) with rapamycin
delays aging and increases healthy longevity in laboratory animals and is used
clinically at high doses to prevent organ transplant rejection and to treat some
forms of cancer. Clinical use of rapamycin is associated with several unwanted
side effects, however, and several strategies are being taken to identify mTORC1
inhibitors with fewer side effects. We describe here a yeast-based growth assay
that can be used to screen for novel inhibitors of mTORC1. By testing compounds
using a wild-type strain and isogenic cells lacking either TOR1 or FPR1, we can
resolve not only whether a compound is an inhibitor of mTORC1 but also whether
the inhibitor acts through a mechanism similar to rapamycin by binding Fpr1.
Using this assay, we show that rapamycin derivatives behave similarly to
rapamycin, while caffeine and the ATP competitive inhibitors Torin 1 and
GSK2126458 are mTORC1 inhibitors in yeast that act independently of Fpr1. Some
mTOR inhibitors in mammalian cells do not inhibit mTORC1 in yeast, and several
nutraceutical compounds were not found to specifically inhibit mTOR but resulted
in a general inhibition of yeast growth. Our screening method holds promise as a
means of effectively assaying drug libraries for mTOR-inhibitory molecules in
vivo that may be adapted as novel treatments to fight diseases and extend healthy
longevity.
PMID- 28707283
TI - Multimodal physical activity increases brain-derived neurotrophic factor levels
and improves cognition in institutionalized older women.
AB - Physical activity has been proposed as a promising intervention to improve
cognition and decrease the risk of dementia in older adults. Brain-derived
neurotrophic factor (BDNF) appears to mediate, at least partially, these effects
of exercise. However, intervention studies of the effects of multimodal exercises
on cognition and BDNF levels are scarce and composed by small samples. Thus, the
generalization of the conclusions of these studies depends on the reproducibility
of the results. In order to contribute to the knowledge on the field, the present
study evaluated the effects of a physical activity intervention composed by
muscle strengthening and aerobic conditioning on BDNF levels and cognition in
older women. Independent and non-demented subjects (>=75 years) were assigned to
a 3-month physical activity intervention (n = 22, 60 min exercise sessions three
times a week) or to a control condition (n = 10, no exercise). Clinical (anxiety
and depression symptoms), neuropsychological (Digit Span, Stroop, Trail Making,
and Contextual Memory tests), physical (upper and lower limb strength, aerobic
conditioning), and physiological (serum BDNF) parameters were evaluated
immediately before, 1 month, and 3 months after starting intervention. Results
indicated that controls had stable levels for all measured variables, whereas the
intervention group improved on physical fitness, depressive symptoms, cognitive
performance, and BDNF levels. Moreover, a linear regression identified an
association between aerobic conditioning and BDNF levels. In conclusion, combined
muscle strengthening and aerobic conditioning was able to improve cognitive
performance and increase BDNF levels. Aerobic conditioning seems to be an
important mediator of these outcomes.
PMID- 28707284
TI - Fixed-Dose Versus Off-Label Combination of Isosorbide Dinitrate Plus Hydralazine
Hydrochloride: Retrospective Propensity-Matched Analysis in Black Medicare
Patients with Heart Failure.
AB - INTRODUCTION: Based upon the findings of the African-American Heart Failure
Trial, the US Food and Drug Administration approved the fixed-dose combination of
isosorbide dinitrate (ISDN) and hydralazine hydrochloride (HYD) (FDC-ISDN/HYD) as
a new drug for treatment of heart failure (HF) in self-identified African
Americans. According to the FDA, FDC-ISDN/HYD has no therapeutic equivalent.
However, off-label combinations of the separate generic drugs ISDN and HYD (OLC
ISDN+HYD) or isosorbide mononitrate (ISMN) and HYD (OLC-ISMN+HYD) are routinely
substituted without any supporting outcome data. We conducted an exploratory
retrospective propensity-matched cohort study using Medicare data to determine
whether a survival difference exists between these treatments in medication
adherent patients. METHODS: Black Medicare beneficiaries with HF were matched
with Medicare Part D data to identify patients with prescriptions to FDC-ISDN/HYD
or the off-label combinations. Only patients with 1-year adherence levels >=80%
were included in the analysis. Propensity-matched scoring created two sets of
matched cohort pairs on a 1:1 basis, each set comparing FDC-ISDN/HYD with one of
the off-label combinations. Kaplan-Meier (KM) survival curves with the log-rank
test were then calculated for each pair for the year of medication adherence.
RESULTS: The analysis population was relatively older (77 years) and mainly
female (66.7%), with a high burden of comorbid disease. The KM estimates of 1
year survival were 87.9% (95% CI 85.6-89.9%) and 83.0% (95% CI 80.3-85.3%) (log
rank p = 0.0024), respectively, for the matched cohorts FDC-ISDN/HYD and OLC
ISDN+HYD (n = 886 in each group) and 88.2% (95% CI 85.9-90.2%) and 84.8% (95% CI
82.2-87.0%) (log rank p = 0.0320), respectively, for the matched cohorts FDC
ISDN/HYD and OLC-ISMN+HYD (n = 868 in each group). CONCLUSION: The 1-year
survival advantage for FDC-ISDN/HYD compared with off-label combinations in
adherent black Medicare beneficiaries with HF suggests a genuine difference
between these medications and warrants prospective investigation.
PMID- 28707285
TI - Burden of Atopic Dermatitis in the United States: Analysis of Healthcare Claims
Data in the Commercial, Medicare, and Medi-Cal Databases.
AB - INTRODUCTION: Comparative data on the burden of atopic dermatitis (AD) in adults
relative to the general population are limited. We performed a large-scale
evaluation of the burden of disease among US adults with AD relative to matched
non-AD controls, encompassing comorbidities, healthcare resource utilization
(HCRU), and costs, using healthcare claims data. The impact of AD disease
severity on these outcomes was also evaluated. METHODS: Adult AD patients in the
Commercial (n = 83,106), Medicare (n = 31,060), and Medi-Cal (n = 5550) databases
were matched (1:1) to non-AD controls by demographic characteristics. AD patients
were stratified by disease severity (higher, lower) using treatment as a
surrogate measure of severity. The comorbidity burden, HCRU, and costs were
evaluated during a 12-month follow-up period. RESULTS: In the Commercial,
Medicare, and Medi-Cal populations, patients with AD had a significantly higher
overall comorbidity burden (P < 0.0001), an increased risk of asthma and allergic
rhinitis (both P < 0.0001), higher HCRU (P < 0.05), and higher mean total per
patient costs (Commercial: US$10,461 versus US$7187; Medicare: US$16,914 versus
US$13,714; Medi-Cal; US$19,462 versus US$10,408; all P < 0.0001), compared with
matched non-AD controls. Higher disease severity was associated with an increased
comorbidity burden (P < 0.0001), HCRU (P < 0.05), and total costs (Commercial:
US$14,580 versus US$7192; Medicare: US$21,779 versus US$12,490; Medi-Cal;
US$22,123 versus US$16,639; all P < 0.0001) relative to lower severity disease.
CONCLUSION: In this large-scale, healthcare claims database analysis, AD patients
had a significantly higher comorbidity burden, HCRU, and costs compared with
matched non-AD controls. Higher disease severity was associated with an even
greater comorbidity and economic burden. FUNDING: Sanofi and Regeneron
Pharmaceuticals, Inc.
PMID- 28707286
TI - Intragastric Balloon Treatment for Obesity: Review of Recent Studies.
AB - INTRODUCTION: The FDA recently approved three intragastric balloon (IGB) devices,
ReShape, ORBERATM, and Obalon for treatment of obesity. Given the high cost,
complication risk, and invasiveness of bariatric surgery, IGB treatment may
present a safer and lower cost option for weight reduction. IGBs are generally
placed in the stomach endoscopically for up to 6 months to reduce gastric
capacity, enhance feelings of fullness, and induce weight loss. The mechanism of
action likely involves stimulation of gastric mechanoreceptors triggering short
acting vagal signals to brain regions implicated in satiety. Balloon efficacy may
be influenced by balloon volume, patient gastric capacity, and treatment
duration. METHODS: This review focused on eight recent (2006-present) randomized
controlled trials (RCTs) comparing percentage total body weight loss (%TBWL)
between IGB and control groups including three reviewed by the FDA. %TBWL based
on the reviewed studies was also compared with bariatric surgery and
pharmacotherapy. RESULTS: Of the eight IGB studies, five had balloon treatment
duration of 6 months. Efficacy at 6 months, based on a pooled weighted-mean
%TBWL, was 9.7%, and the control-subtracted %TBWL was 5.6%. When one study
without SDs was removed, the weighted mean %TBWL was 9.3 +/- 5.7% SD, and control
subtracted %TBWL was 5.5 +/- 7.8%, which was statistically greater than controls.
IGB showed lower efficacy than bariatric surgery (median weight loss of 27% for
Rouen-Y gastric bypass (RYGB). The control-subtracted %TBWL over 6 months of 5.5
5.6% is less than the most efficacious FDA-approved weight loss drug, Qsymia. At
the recommended dose, Qsymia has a placebo-subtracted %TBWL at 6 months of
approximately 6.6%. The weighted mean reported incidence of serious adverse
events (SAEs) in the IGB group across all eight studies was 10.5%. Only six of
the eight reviewed studies reported adverse events (AEs) in the IGB group, with a
pooled reported incidence of 28.2%. Recently, the FDA reported new AEs including
acute pancreatitis with ReShape and ORBERATM. CONCLUSION: Based on the available
evidence, it is unlikely that IGB use will supplant other forms of obesity
treatment. The estimated cost of endoscopic balloon implantation and retrieval is
US $8,150. Collectively, a relatively small control-subtracted %TBWL and the
potential for serious complications makes IGB unlikely to become widely adopted.
Given the recent FDA warning, IGB longevity on the market is questionable.
PMID- 28707287
TI - Are the Origins of Precision Medicine Found in the Corpus Hippocraticum?
AB - Precision medicine (PM) is currently placed at the center of global attention
following decades of research towards the improvement of medical practice. The
subject of this study was to examine whether this trend had emerged earlier, in
fact if the fundamentals of PM can be traced back to the ancient Greek era. For
this reason, we studied the collection of all the Hippocratic texts, called the
Corpus Hippocraticum, using original translations, and attempted an
interpretation of the ancient authors in the context of the modern concept of PM.
The most important points located in the ancient passages were: (1) medicine in
not 'absolute', thus its directions cannot be generalized to everybody, (2) each
human body/organism is different and responds differently to therapy; therefore,
the same treatment cannot be suitable for everybody and (3) the physician should
choose the appropriate treatment, depending on the patients' individual
characteristics, such as different health status and life style (activities,
diet, etc.). Although the ancient 'precision medicine' is different from its
modern description, the latter derived from well-established experimental
conclusions, it becomes apparent that there is a common conception, aiming to
achieve more effective healing by focusing on the individual.
PMID- 28707288
TI - Atrial fibrillation risk evaluation in patients with generalised anxiety
disorders: the role of electrocardiographic parameters. Commentary to the
article: "Atrial electromechanical delay analysed by tissue Doppler
echocardiography...".
PMID- 28707289
TI - Polish Forum for Prevention Guidelines on Diabetes: update 2017.
PMID- 28707290
TI - Takotsubo syndrome after bone cement injection during hip replacement.
PMID- 28707291
TI - Pre-hospital cardiac arrest treated successfully with automated external
defibrillator.
PMID- 28707292
TI - Rupture of ventricular septum leading to acute heart failure due to myocardial
infarction of the inferior heart wall.
PMID- 28707293
TI - Coronary septic embolism: an unusual presentation of acute myocardial infarction.
PMID- 28707294
TI - Long-term follow-up in a pregnant patient with severe aortic stenosis complicated
by pulmonary oedema and cardiac arrest treated with cardiopulmonary bypass
surgery.
PMID- 28707295
TI - Repetitive stent thrombosis in a patient with suspected allergy to aspirin and
multiple switch between clopidogrel, prasugrel, and ticagrelor.
PMID- 28707296
TI - Ebp1 regulates myogenic differentiation of myoblast cells via SMAD2/3 signaling
pathway.
AB - Regulation of skeletal muscle development requires many of the regulatory
networks that are fundamental to developmental myogenesis. ErbB3 binding protein
1 (Ebp1) is involved in the control of myoblasts development in chicken. However,
the expression and biological functions of Ebp1 in the progress of myogenesis are
unclear. This study focused on determining the effect of Ebp1 on myogenic
proliferation and differentiation using a primary myoblasts culture model. Ebp1
was found to upregulate in proliferating myoblasts and decrease at the early
stage of myogenic differentiation. The level of endogenous Ebp1 increased from E9
to E20 chicken leg muscles. Knockdown of Ebp1 had no effect on myoblasts
proliferation. However, myogenic differentiation into multinucleated myotubes was
significantly reduced. The mRNA and protein expression of MRFs was decreased when
Ebp1 was knocked down. Downregulation of Ebp1, accompanied by elevated levels of
pSMAD2/3, suggests that Ebp1 is involved in regulating myogenic differentiation
via SMAD2/3 inhibition. The phosphorylation of SMAD2/3 was activated and the
expression of MYOD and MYOG was reduced in Ebp1 knockdown myoblasts, but addition
of LY2109761 (an inhibitor specified to SMAD2/3) blocked these effects.
Collectively, these results indicate that Ebp1 promotes myoblast differentiation
by inhibition of SMAD2/3 signaling pathway during chicken myogenesis. These data
provide new insights into the biological role of Ebp1 in embryonic chicken
skeletal muscle development.
PMID- 28707297
TI - Functional gastrointestinal disorders in children from low socio-economic status
and Helicobacter pylori infection.
AB - BACKGROUND: Most studies on functional gastrointestinal disorders (FGIDs) in
children are based on data from the northern hemisphere. Scientific reports are
arising in South American population, but little is still known about children
from low socio-economic status (SES), where Helicobacter pylori infection is
endemic. Our objective was to evaluate the prevalence of FGIDs in school children
from low SES and its relationship with H. pylori infection. METHODS: Children
from 3 public schools of low SES from Santiago de Chile were included. Students
completed the Rome III Questionnaire and a survey about other symptoms. Also, the
13 C urea breath test determined the presence of H. pylori infection. RESULTS:
Five hundred six children were included, where 48% were male, with a median age
of 15.7 years (range 7.1-19.6). Forty-two percent had some FGID, aerophagia and
functional constipation being the most frequent. Females (adjusted OR 1.5, 95% CI
[1.1, 2.2]), those children with parents within the lowest level of education
(adjusted OR 1.6, 95% CI: 1.1-2.4), and family history of gastric cancer
(adjusted OR 1.9, 95% CI: 1.2-3.1) were related to FGIDs. The prevalence of H.
pylori infection was 55.9% (95% CI [50.7, 60.9]). In multivariable analysis, the
presence of abdominal pain (OR 1.55, 95% CI [1.02, 2.36]), but not FGIDs, was
related to H. pylori infection. CONCLUSIONS: FGIDs are common in low SES
students. A low educational level of the household head, family history of
gastric cancer. and being female are related to the development of FGIDs. In this
study, no relationship between the presence of H. pylori and FGIDs was found.
PMID- 28707299
TI - Detection of gene-environment interactions in a family-based population using
SCAD.
AB - Gene-environment interaction (GxE) is emphasized as one potential source of
missing genetic variation on disease traits, and the ultimate goal of GxE
research is prediction of individual risk and prevention of complex diseases.
However, there are various challenges in statistical analysis of GxE. In this
paper, we focus on the three methodological challenges: (i) the high dimensions
of genes; (ii) the hierarchical structure between interaction effects and their
corresponding main effects; and (iii) the correlation among subjects from family
based population studies. In this paper, we propose an algorithm that approaches
all three challenges simultaneously. This is the first penalized method focusing
on an interaction search based on a linear mixed effect model. For verification,
we compare the empirical performance of our new method with other existing
methods in simulation study. The results demonstrate the superiority of our
method under overall simulation setup. In particular, the outperformance
obviously becomes greater as the correlation among subjects increases. In
addition, the new method provides a robust estimate for the correlation among
subjects. We also apply the new method on Genetics of Lipid Lowering Drugs and
Diet Network study data. Copyright (c) 2017 John Wiley & Sons, Ltd.
PMID- 28707298
TI - Melatonin receptors: molecular pharmacology and signalling in the context of
system bias.
AB - Melatonin, N-acetyl-5-methoxytryptamine, an evolutionally old molecule, is
produced by the pineal gland in vertebrates, and it binds with high affinity to
melatonin receptors, which are members of the GPCR family. Among the multiple
effects attributed to melatonin, we will focus here on those that are dependent
on the activation of the two mammalian MT1 and MT2 melatonin receptors. We
briefly summarize the latest developments on synthetic melatonin receptor
ligands, including multi-target-directed ligands, and the characterization of
signalling-biased ligands. We discuss signalling pathways activated by melatonin
receptors that appear to be highly cell- and tissue-dependent, emphasizing the
impact of system bias on the functional outcome. Different proteins have been
demonstrated to interact with melatonin receptors, and thus, we postulate that
part of this system bias has its molecular basis in differences of the expression
of receptor-associated proteins including heterodimerization partners. Finally,
bias at the level of the receptor, by the expression of genetic receptor
variants, will be discussed to show how a modified receptor function can have an
effect on the risk for common diseases like type 2 diabetes in humans.
PMID- 28707300
TI - High Conductivity and Electron-Transfer Validation in an n-Type Fluoride-Anion
Doped Polymer for Thermoelectrics in Air.
AB - Air-stable and soluble tetrabutylammonium fluoride (TBAF) is demonstrated as an
efficient n-type dopant for the conjugated polymer ClBDPPV. Electron transfer
from F- anions to the pi-electron-deficient ClBDPPV through anion-pi electronic
interactions is strongly corroborated by the combined results of electron spin
resonance, UV-vis-NIR, and ultraviolet photoelectron spectroscopy. Doping of
ClBDPPV with 25 mol% TBAF boosts electrical conductivity to up to 0.62 S cm-1 ,
among the highest conductivities that have been reported for solution-processed n
type conjugated polymers, with a thermoelectric power factor of 0.63 uW m-1 K-2
in air. Importantly, the Seebeck coefficient agrees with recently published
correlations to conductivity. Moreover, the F- -doped ClBDPPV shows significant
air stability, maintaining the conductivity of over 0.1 S cm-1 in a thick film
after exposure to air for one week, to the best of our knowledge the first report
of an air-stable solution-processable n-doped conductive polymer with this level
of conductivity. The result shows that using solution-processable small-anion
salts such as TBAF as an n-dopant of organic conjugated polymers possessing lower
LUMO (lowest unoccupied molecular orbital), less than -4.2 eV) can open new
opportunities toward high-performance air-stable solution-processable n-type
thermoelectric (TE) conjugated polymers.
PMID- 28707301
TI - The role of wing geometric morphometrics in the identification of sandflies
within the subgenus Lutzomyia.
AB - The Lutzomyia subgenus (Diptera: Psychodidae) includes sibling species with
morphologically indistinguishable females. The aims of this study were to analyse
variations in the size and shape of wings of species within the Lutzomyia
subgenus and to assess whether these analyses might be useful in their
identification. Wings (n = 733) of 18 species deposited in Brazilian collections
were analysed by geometric morphometrics, using other genera and subgenera as
outgroups. Shape variation was summarized in multivariate analyses and
differences in wing size among species were tested by analysis of variance. The
results showed significant variation in the sizes and shapes of wings of
different Lutzomyia species. Two clusters within the Lutzomyia subgenus were
distinguished in analyses of both males and females. In Cluster 1 (Lutzomyia
ischnacantha, Lutzomyia cavernicola, Lutzomyia almerioi, Lutzomyia forattinii,
Lutzomyia renei and Lutzomyia battistinii), scores for correct reclassification
were high (females, kappa = 0.91; males, kappa = 0.90), whereas in Cluster 2
(Lutzomyia alencari, Lutzomyia ischyracantha, Lutzomyia cruzi, Lutzomyia
longipalpis, Lutzomyia gaminarai and Lutzomyia lichyi), scores for correct
reclassification were low (females, kappa = 0.42; males, kappa = 0.48). Wing
geometry was useful in the identification of some species of the Lutzomyia
subgenus, but did not allow the identification of sibling species such as L.
longipalpis and L. cruzi.
PMID- 28707302
TI - Dialysate sodium and intradialytic hypotension.
AB - Intradialytic hypotension (IDH) is a common complication in hemodialysis,
particularly with the time and frequency constraints of standard session delivery
in contemporary practice. High intradialytic weight gain (IDWG), high
ultrafiltration rates (UFR), and frequent IDH are highly interlinked, and
separately or together contribute to the high cardiovascular morbidity and
mortality observed in the hemodialysis population. Using a lower concentration of
sodium in the dialysate (D-Na) reduces sodium delivery to the patient during
dialysis, and several studies reported the beneficial effect in controlling IDWG,
UFR, and hypertension. On the other hand, high dialysate sodium is associated
with more hemodynamic benefits in an unstable patient. The resulting sodium
loading may, however, induce a vicious cycle of higher IDWG, requiring more rapid
ultrafiltration, eventually contributing to intradialytic symptoms and
hypotension. In this article, we review the available literature on fixed and
profiled dialysate sodium prescriptions, and we recommend a tailored approach
that considers the patient's status to optimize dialysis delivery.
PMID- 28707303
TI - Prediction of geriatric rehabilitation outcomes: Comparison between three
cognitive screening tools.
AB - AIM: Comparison between the predictions of functional rehabilitation outcomes at
a department of geriatric rehabilitation using three cognitive screening tools -
Mini Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and
Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). METHODS:
This study is a prospective study. The study participants were 212 patients aged
65 and older admitted to rehabilitation departments at a geriatric facility in
central Israel, from April 2016 to October 2016. The cognitive functioning of
each patient was assessed using the MMSE, MoCA, and IQCODE. Upon discharge,
rehabilitation outcomes were examined using the Functional Independence Measure
(FIM), cognitive FIM, delta FIM (Delta FIM), and ADL. RESULTS: Cognitive
impairment was found to interfere with the rehabilitation process. The MMSE was
the best predictor of functional rehabilitation outcomes at discharge, compared
to the IQCODE, while the MoCA did not predict these measures. In addition, when
distinguishing between patients by ethnicity (Jewish versus Arab), the MMSE and
the IQCODE predicted FIM upon discharge among Jewish patients, while only the
IQCODE predicted FIM upon discharge among Arab patients. CONCLUSIONS: The
research findings show that cognitive assessment upon admission for
rehabilitation - MMSE among Jewish patients and IQCODE among Arab patients - can
help predict functional rehabilitation outcomes and make the appropriate
adaptations in the rehabilitation program. Geriatr Gerontol Int 2017; 17: 2507
2513.
PMID- 28707304
TI - Actigraph measures of sleep among female hospital employees working day or
alternating day and night shifts.
AB - Sleep disturbance is common among shift workers, and may be an important factor
in the effect of shift work on chronic disease development. In this cross
sectional study, we described sleep patterns of 294 female hospital workers (142
alternating day-night shift workers, 152 day workers) and determined associations
between shift work and sleep duration. Rest-activity cycles were recorded with
the ActiGraph GT3X+ for 1 week. Analyses were stratified by chronotype of shift
workers. Using all study days to calculate average sleep duration, shift workers
slept approximately 13 min less than day workers during main sleep periods, while
24-h sleep duration did not differ between day workers and shift workers. Results
from age-adjusted models demonstrated that all shift workers, regardless of
chronotype, slept 20-30 min less than day workers on day shifts during main and
total sleep. Early and intermediate chronotypes working night shifts slept
between 114 and 125 min less than day workers, both with regard to the main sleep
episode and 24-h sleep duration, while the difference was less pronounced among
late chronotypes. When sleep duration on free days was compared between shift
workers and day workers, only shift workers with late chronotypes slept less, by
approximately 50 min, than day workers during main sleep. Results from this study
demonstrate how an alternating day-night shift work schedule impacts sleep
negatively among female hospital workers, and the importance of considering
chronotype in sleep research among shift workers.
PMID- 28707306
TI - Current reinforcement model reproduces center-in-center vein trajectory of
Physarum polycephalum.
AB - Vein networks span the whole body of the amoeboid organism in the plasmodial
slime mould Physarum polycephalum, and the network topology is rearranged within
an hour in response to spatio-temporal variations of the environment. It has been
reported that this tube morphogenesis is capable of solving mazes, and a
mathematical model, named the 'current reinforcement rule', was proposed based on
the adaptability of the veins. Although it is known that this model works well
for reproducing some key characters of the organism's maze-solving behaviour, one
important issue is still open: In the real organism, the thick veins tend to
trace the shortest possible route by cutting the corners at the turn of
corridors, following a center-in-center trajectory, but it has not yet been
examined whether this feature also appears in the mathematical model, using
corridors of finite width. In this report, we confirm that the mathematical model
reproduces the center-in-center trajectory of veins around corners observed in
the maze-solving experiment.
PMID- 28707305
TI - Controlled basic fibroblast growth factor release device made of
poly(ethyleneglycol) dimethacrylates for creating a subcutaneous neovascular bed
for cell transplantation.
AB - Subcutaneous space is a potential site for the transplantation of cells such as
islets for treatment of type 1 diabetes. To enhance engraftment, an optimal space
for the growth of the transplanted cells is needed along with neovascularization.
In this study, we developed a device using a photocurable resin,
poly(ethyleneglycol) dimethacrylates (PEGDM), for controlled release of basic
fibroblast growth factor (bFGF) to create a subcutaneous neovascular bed in rats.
The device consists of a disk-shaped capsule with micropores and is composed of
tri(ethyleneglycol) dimethacrylate (TEGDM) and a drug formulation of PEGDM. The
release rate was tuned by changing the number of pores and the composition of
water and PEGDM in the drug formulation. bFGF released from devices incubated in
phosphate-buffered saline (PBS) enhanced the growth of fibroblasts, indicating
bioactivity of bFGF after release. Histological evaluation showed a significant
increase in the extent of vasculature that was dependent on the amount of bFGF
loaded into the device. A perfusion study using fluorescein isothiocyanate
dextran 2000 kDa showed linear and capillary staining patterns, indicating potent
functional vasculature. In conclusion, the controlled bFGF releasing device could
provide a neovascular bed with the required vascularization in the subcutaneous
space. (c) 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 3017
3024, 2017.
PMID- 28707307
TI - Fine Tuning of MOF-505 Analogues To Reduce Low-Pressure Methane Uptake and
Enhance Methane Working Capacity.
AB - We present a crystal engineering strategy to fine tune the pore chemistry and CH4
-storage performance of a family of isomorphic MOFs based upon PCN-14. These MOFs
exhibit similar pore size, pore surface, and surface area (around 3000 m2 g-1 )
and were prepared with the goal to enhance CH4 working capacity. [Cu2 (L2)(H2 O)2
]n (NJU-Bai 41: NJU-Bai for Nanjing University Bai's group), [Cu2 (L3)(H2 O)2 ]n
(NJU-Bai 42), and [Cu2 (L4)(DMF)2 ]n (NJU-Bai 43) were prepared and we observed
that the CH4 volumetric working capacity and volumetric uptake values are
influenced by subtle changes in structure and chemistry. In particular, the CH4
working capacity of NJU-Bai 43 reaches 198 cm3 (STP: 273.15 K, 1 atm) cm-3 at 298
K and 65 bar, which is amongst the highest reported for MOFs under these
conditions and is much higher than the corresponding value for PCN-14 (157 cm3
(STP) cm-3 ).
PMID- 28707308
TI - Baseline anemia in patients undergoing percutaneous coronary intervention after
an acute coronary syndrome-A paradox of high bleeding risk, high ischemic risk,
and complex coronary disease.
AB - OBJECTIVES: To define more clearly the associations between baseline anemia,
bleeding/ischemia risk, coronary disease severity, and outcomes by
revascularization completeness. BACKGROUND: Anemia is associated with adverse
outcomes in patients presenting with an acute coronary syndrome (ACS). METHODS
AND RESULTS: Data was sourced from hospital databases for patients admitted with
an ACS to a single center between 2011 and 2014. Using WHO anemia criteria, 468
(26.9%) of 1731 patients were anemic. In anemic patients, the mean CRUSADE score
(34.6 +/- 16.9 vs 24.6 +/- 13.4, P < 0.0001), mean GRACE scores (165.8 +/- 44.9
vs 141.6 +/- 40.1, P < 0.0001), and percentage of patients with a high/very high
CRUSADE score combined with a high GRACE score (69.3 vs 48.3%, P < 0.0001) was
much greater than non-anemic patients. Patients with baseline anemia were more
likely to have left main or chronic occlusive disease, and more diseased vessels.
The percentage of patients with residual disease (41.2 vs 30.7%, P < 0.0001), the
number of residual diseased vessels (0.59 +/- 0.83 vs 0.42 +/- 0.72, P < 0.0001),
and the percentage with a residual CTO (62.4 vs 56.4%, P = 0.036) were all higher
than in non-anemic patients. The duration of anti-platelet therapy was
significantly shorter in anemic patients (7.8 +/- 4.3 vs 11.2 +/- 2.4 months, P <
0.001). At 12-months, mortality and stent thrombosis were more likely to occur in
anemic patients, with the number of residual vessels associated with adverse
survival regardless of anemia status. CONCLUSIONS: Patients with anemia present
with high ischemia and bleed risk scores, complex coronary disease, and have
adverse outcomes. Incomplete revascularization was associated with worse survival
regardless of anemia status.
PMID- 28707309
TI - Low-Temperature Soft-Cover Deposition of Uniform Large-Scale Perovskite Films for
High-Performance Solar Cells.
AB - Large-scale high-quality perovskite thin films are crucial to produce high
performance perovskite solar cells. However, for perovskite films fabricated by
solvent-rich processes, film uniformity can be prevented by convection during
thermal evaporation of the solvent. Here, a scalable low-temperature soft-cover
deposition (LT-SCD) method is presented, where the thermal convection-induced
defects in perovskite films are eliminated through a strategy of surface tension
relaxation. Compact, homogeneous, and convection-induced-defects-free perovskite
films are obtained on an area of 12 cm2 , which enables a power conversion
efficiency (PCE) of 15.5% on a solar cell with an area of 5 cm2 . This is the
highest efficiency at this large cell area. A PCE of 15.3% is also obtained on a
flexible perovskite solar cell deposited on the polyethylene terephthalate
substrate owing to the advantage of presented low-temperature processing. Hence,
the present LT-SCD technology provides a new non-spin-coating route to the
deposition of large-area uniform perovskite films for both rigid and flexible
perovskite devices.
PMID- 28707310
TI - Sleep deprivation in interventional cardiology: Implications for patient care and
physician-health.
AB - The burden and impact of sleep deprivation on both patient care and on the health
of interventional cardiologists is not well understood. Due to the nature of
emergent procedures occurring in the cardiac catheterization laboratory,
interventionalists are prone to suffer from acute and/or chronic sleep
deprivation. Sleep deprivation has been associated with numerous adverse effects,
such as impaired performance, cognitive deficits, reduced psychomotor vigilance,
and workplace errors and injuries, among many others. Although sleep deprivation
has been linked to more errors in trainees, there is paucity of data addressing
outcomes in interventional cardiology. The purpose of this overview is to explore
the possible impact of sleep deprivation on interventional cardiology in relation
to patient care and physician health, and examine potential approaches to this
issue.
PMID- 28707311
TI - Dynamic contrast-enhanced MRI of the patellar bone: How to quantify perfusion.
AB - PURPOSE: To identify the optimal combination of pharmacokinetic model and
arterial input function (AIF) for quantitative analysis of blood perfusion in the
patellar bone using dynamic contrast-enhanced magnetic resonance imaging (DCE
MRI). MATERIALS AND METHODS: This method design study used a random subset of
five control subjects from an Institutional Review Board (IRB)-approved case
control study into patellofemoral pain, scanned on a 3T MR system with a contrast
enhanced time-resolved imaging of contrast kinetics (TRICKS) sequence. We
systematically investigated the reproducibility of pharmacokinetic parameters for
all combinations of Orton and Parker AIF models with Tofts, Extended Tofts
(ETofts), and Brix pharmacokinetic models. Furthermore, we evaluated if the AIF
should use literature parameters, be subject-specific, or group-specific. Model
selection was based on the goodness-of-fit and the coefficient of variation of
the pharmacokinetic parameters inside the patella. This extends previous studies
that were not focused on the patella and did not evaluate as many combinations of
arterial and pharmacokinetic models. RESULTS: The vascular component in the
ETofts model could not reliably be recovered (coefficient of variation [CV] of vp
>50%) and the Brix model parameters showed high variability of up to 20% for kel
across good AIF models. Compared to group-specific AIF, the subject-specific
AIF's mostly had higher residual. The best reproducibility and goodness-of-fit
were obtained by combining Tofts' pharmacokinetic model with the group-specific
Parker AIF. CONCLUSION: We identified several good combinations of
pharmacokinetic models and AIF for quantitative analysis of perfusion in the
patellar bone. The recommended combination is Tofts pharmacokinetic model
combined with a group-specific Parker AIF model. LEVEL OF EVIDENCE: 2 Technical
Efficacy: Stage 1 J. Magn. Reson. Imaging 2018;47:848-858.
PMID- 28707312
TI - Selective Palladium(II)-Catalyzed Carbonylation of Methylene beta-C-H Bonds in
Aliphatic Amines.
AB - Palladium(II)-catalyzed C-H carbonylation reactions of methylene C-H bonds in
secondary aliphatic amines lead to the formation of trans-disubstituted beta
lactams in excellent yields and selectivities. The generality of the C-H
carbonylation process is aided by the action of xantphos-based ligands and is
important in securing good yields for the beta-lactam products.
PMID- 28707313
TI - Predictive factors for publication of abstracts at the Royal Australasian College
of Surgeons Annual Scientific Congress.
AB - BACKGROUND: A key metric of the research quality of medical conferences is the
publication rate of abstracts. The study objective was to determine the
publication rate of abstracts presented at the Royal Australasian College of
Surgeons Annual Scientific Congress (RACS ASC) and to examine for any predictive
factors associated with publication. METHODS: Abstracts presented at the RACS ASC
from 2011 to 2013 were analysed. Abstract characteristics such as presentation
format, study type, study design, study site, cohort size and author origin were
recorded. Abstracts published were identified by a PubMed search using a strict
algorithm. Univariate and multivariable logistic regressions were used to analyse
for predictive factors of publication. RESULTS: Overall, 1438 abstracts were
presented and 423 abstracts (29%) were published. The median time to publication
was 15.2 months (interquartile range: 8-26) with 110 in Australasian journals
(26%). The median number of citations for published abstracts was 6
(interquartile range: 2-16). After multivariable analysis, publication was
significantly associated with prospective study design (odds ratio (OR) = 1.34, P
= 0.02), multicentre study site (OR = 1.43, P = 0.02), cohort size >=100 (OR =
2.00, P < 0.001) and New Zealand author origin (OR = 1.50, P = 0.01). CONCLUSION:
Our study demonstrates that less than one-third of abstracts presented at the
RACS ASC are subsequently published in a peer-reviewed journal. Factors
significantly associated with journal publication include prospective studies,
multicentre study, a larger cohort size and New Zealand author origin. Advances
in surgery may progress from the preliminary findings of conference abstracts.
However only after the rigorous peer review offered by journal publication should
changes in decision-making of patient care occur.
PMID- 28707314
TI - Nodular lymphocyte predominant Hodgkin's lymphoma in daily practice: A
multicenter experience.
AB - Nodular lymphocyte predominant Hodgkin's lymphoma (NLPHL) is a rare subtype of
Hodgkin's lymphoma. In this study, we aimed to investigate the clinical features
and therapeutic outcomes of patients with NLPHL who were diagnosed at different
institutes in Turkey. We retrospectively reviewed the records of the patients
diagnosed with NLPHL. Adult patients who were diagnosed after 2005 with
histological confirmation were selected for the study. Forty-three patients were
included in the study. Median age of patients was 37.5 years (18-70) at the time
of diagnosis. About 60.5% patients were diagnosed as stage I and II NLPHL, and
remaining 39.5% had stage III and IV disease. Median follow-up was 46 months.
During follow-up, none of the patients died. Seven patients relapsed or
progressed after initial therapy at a median of 12 months. Five of 7
relapsed/refractory patients (71.4%) were salvaged with chemotherapy only (DHAP,
ICE), and the remaining 2 (28.6%) were salvaged with chemoimmunotherapy. All of
relapsed/refractory patients were able to achieve complete remission after
salvage therapy. Lactate dehydrogenase levels were significantly higher in
patients with progressive disease compared with nonprogressive disease. Our study
showed an excellent outcome with all patients alive at last contact with a median
follow up of 46 months despite a wide range of different therapeutic approaches.
All relapsed and refractory patients were successfully salvaged despite a low
frequency of patients received immunotherapy in conjunction with chemotherapy.
Our results suggest that immunotherapy may be reserved for further relapses.
PMID- 28707315
TI - Dissolution behavior of CaO-MgO-SiO2 -based multiphase bioceramic powders and
effects of the released ions on osteogenesis.
AB - In the present study, the dissolution behavior of the CaO-MgO-SiO2 -based
multiphase bioceramic powders as well as the effects of released ions on
osteogenesis was investigated. In the dissolution process, Ca, Mg, and Si ions
could be dissolved out from the powders. The incorporation of Mg could slow down
the degradation rate of the powders so that to reduce the local concentration of
Ca and Si ions. In return, the dissolution of Ca and Si ions leading to the
formation of a porous SiO2 -rich layer could enhance the readsorption of free Mg
ions in solution and thus down-regulate the concentration of Mg ions. In
addition, the released ions exhibited both positive and negative synergistic
effects on osteogenesis with a concentration-dependent manner. Trace amount of
released Si ions could stimulate cell proliferation and osteogenic
differentiation in the presence of Ca and Mg ions. The optimal concentration of
Ca-Mg-Si ion combination to promote osteogenesis was existed in the 1/4 diluted
extract, whereas a slightly inhibitory effect on cell proliferation and ALP
activity was observed in the 1/2 diluted extract with higher concentration of Ca
and Si ions . All above results suggested that the ion dissolution behavior of
the CaO-MgO-SiO2 -based multiphase bioceramic could be regulated via adjustment
of the composition so that released ions could be maintained at an appropriate
composite concentration to cooperatively regulate the osteogenesis. This research
provided an experimental basis for further optimization and application of CaO
MgO-SiO2 -based multiphase bioceramics with controlled ion dissolution and
excellent physicochemical and biological properties. (c) 2017 Wiley Periodicals,
Inc. J Biomed Mater Res Part A: 105A: 3159-3168, 2017.
PMID- 28707316
TI - TIcaGrEloR and Absorb bioresorbable vascular scaffold implantation for recovery
of vascular function after successful chronic total occlusion recanalization
(TIGER-BVS trial): Rationale and study design.
AB - OBJECTIVES: To explore the role of ticagrelor versus clopidogrel in coronary
blood flow normalization immediately after chronic coronary total occlusion (CTO)
recanalization. BACKGROUND: Coronary vascular function of a CTO immediately after
recanalization is demonstrated to be poor. METHODS: The TIGER BVS is a
prospective, double-randomized, open-label, two parallel-group controlled
clinical trial to evaluate efficacy of ticagrelor versus clopidogrel in improving
vascular function of coronary segment distal to CTO immediately after CTO
recanalization. A total of 50 patients who receive CTO PCI will be randomized 1:1
to receive ticagrelor versus clopidogrel at least 3 days before the procedure.
Immediately after CTO recanalization with Absorb BVS implantation, a specific
study of vascular function under adenosine infusion will be performed. Patients
will be therefore randomized 1:1 to receive angiographic follow-up with vascular
function and optical coherence tomography analyses at 1- or 3-year follow-up.
This study is registered on ClinicalTrials.gov with number NCT02211066.
CONCLUSIONS: The TIGER BVS trial will provide the first randomized comparison
between ticagrelor versus clopidogrel in recovering vascular function in CTO
patients. It will also provide important data on vascular restoration therapy of
Absorb BVS in this scenario.
PMID- 28707317
TI - Acral lentiginous melanoma: a skin cancer with unfavourable prognostic features.
A study of the German central malignant melanoma registry (CMMR) in 2050
patients.
AB - BACKGROUND: Acral lentiginous melanoma (ALM) is one of the four major subtypes in
cutaneous melanoma (CM). Although ALM has a poorer prognosis than other CM
subtypes, the prognostic factors associated with ALM have only been verified in
small-sized cohorts because of the low incidence of ALM worldwide. OBJECTIVES: To
investigate the clinical characteristics of ALM and to evaluate their prognostic
values based on a large dataset from the Central Malignant Melanoma Registry
(CMMR) of the German Dermatologic Society. METHODS: The Kaplan-Meier method was
used to estimate the potential influence of clinical and histological parameters
on ALM disease-specific survival (DSS) curves, which were compared using the log
rank test. A Cox proportional hazards model was used to identify independent
prognostic factors for DSS. RESULTS: In total, 2050 patients with ALM were
identified from 58 949 patients with CM recorded by the CMMR with follow-up data.
In multivariate analyses, age (P = 0.006), ulceration (P = 0.013), tumour
thickness (P < 0.001) and tumour spread (P < 0.001) turned out to be significant
prognostic factors for DSS in ALM whereas sex, nevus association and level of
invasion were not independent factors. CONCLUSIONS: ALM has the same prognostic
factors as other subtypes of melanoma. Unfavourable prognosis probably derives
from the delay in diagnosis in comparison with other melanoma subtypes.
PMID- 28707318
TI - Correlation of Xiphopubic Distance, Body Weight, Height and Body Mass Index with
Intravesical and Abdominal Initial Resting Pressures in Urodynamic Testing in the
Sitting Position.
AB - OBJECTIVES: To compare the initial resting intravesical pressure (pves ) and
abdominal pressure (pabd ) in the sitting position with the typical range of
values, to assess the correlation between such pressures and patient xipho-pubic
distance, body weight, height and body mass index (BMI), and to estimate if xipho
pubic distance can be a guide to interpret initial resting pressures in
urodynamic testing. METHODS: Women with lower urinary tract symptomatology
referred for urodynamic testing were consecutively enrolled in a prospective
study. Conventional cystometry was done following "good urodynamic practices".
The correlation between initial resting pves and pabd and xipho-pubic distance,
body weight, height and BMI were studied using simple and multiple linear
regression analysis. Statistical significance was defined as P < 0.05. RESULTS:
One hundred women aged (mean +/- SD) 59.2 +/- 13.3 were studied. There was a
significant correlation between both pves and pabd , and xipho-pubic distance,
body weight and BMI and no correlation with height. Over the multiple analysis,
xipho-pubic distance and body weight correlated independently with pves ; body
weight correlated independently with pabd . Three patients had pves and/or pabd
out of typical range, with BMIs values of 18.48, 18.72 and 35.81 kg/m2 . There
was a wide range of difference between xipho-pubic distance and initial resting
pressures. CONCLUSIONS: Out of range initial resting pressures occur in
underweight (or close to) or severely obese patients. Xipho-pubic distance and
body weight correlated independently with pves . Body weight correlated
independently with pabd . Xipho-pubic distance cannot be a guide to interpret the
initial resting pressures.
PMID- 28707319
TI - Tenofovir disoproxil fumarate significantly decreases serum lipoprotein levels
compared with entecavir nucleos(t)ide analogue therapy in chronic hepatitis B
carriers.
AB - BACKGROUND: Tenofovir disoproxil fumarate (TDF) and entecavir (ETV) are first
line treatments for chronic hepatitis B (CHB). Studies suggest lipid lowering
effect of TDF in human immunodeficiency virus positive (HIV+) individuals, but
the effect on lipids and cardiovascular disease (CVD) risk in CHB is unknown.
AIM: To compare TDF vs ETV effects on lipid levels in CHB. METHODS: In this
retrospective cohort study, data on serum lipids and CVD risk factors at baseline
and ~1 year on TDF or ETV were collected from CHB carriers. We used propensity
score matched models to assess the effect on total cholesterol (TC), LDL-C, HDL
and triglycerides (TGL). RESULTS: In 348 patients, median age was 57 (IQR: 47-65
years), 63% were male, 77% were Asian, 19% were cirrhotic, 25% were HBeAg
positive at baseline, and 72% received TDF vs 28% ETV. ETV-treated patients were
older (median age: 60 vs 55, P<.01), had similar smoking and hypertension rates,
but diabetes and dyslipidemia were more prevalent (19% vs 9%, P=.01; 14% vs 6%,
P=.05, respectively). In propensity score matched models for age, gender, usage
of lipid lowering agents, dyslipidemia and diabetes, TDF-treated patients were
more likely to show a 20% decrease in TC (95% CI: 3%-25%), LDL-C (95% CI: 1%-25%)
and HDL-C (CI: 10%-30%) levels compared with those on ETV. No change in TGL was
observed in either group. CONCLUSIONS: A greater decline in TC, LDL-C and HDL was
observed in CHB carriers receiving TDF compared with ETV. These data may
influence anti-viral choice in CHB carriers at risk for CVD.
PMID- 28707320
TI - Homology model of the human tRNA splicing ligase RtcB.
AB - RtcB is an essential human tRNA ligase required for ligating the 2',3'-cyclic
phosphate and 5'-hydroxyl termini of cleaved tRNA halves during tRNA splicing and
XBP1 fragments during endoplasmic reticulum stress. Activation of XBP1 has been
implicated in various human tumors including breast cancer. Here we present, for
the first time, a homology model of human RtcB (hRtcB) in complex with manganese
and covalently bound GMP built from the Pyrococcus horikoshii RtcB (bRtcB)
crystal structure, PDB ID 4DWQA. The structure is analyzed in terms of
stereochemical quality, folding reliability, secondary structure similarity with
bRtcB, druggability of the active site binding pocket and its metal-binding
microenvironment. In comparison with bRtcB, loss of a manganese-coordinating
water and movement of Asn226 (Asn202 in 4DWQA) to form metal-ligand coordination,
demonstrates the uniqueness of the hRtcB model. Rotation of GMP leads to the
formation of an additional metal-ligand coordination (Mn-O). Umbrella sampling
simulations of Mn binding in wild type and the catalytically inactive C122A
mutant reveal a clear reduction of Mn binding ability in the mutant, thus
explaining the loss of activity therein. Our results furthermore clearly show
that the GTP binding site of the enzyme is a well-defined pocket that can be
utilized as target site for in silico drug discovery.
PMID- 28707322
TI - Development and validation of a risk model for long-term mortality after
percutaneous coronary intervention: The IDEA-BIO Study.
AB - OBJECTIVES: We aimed to develop a model to predict long-term mortality after
percutaneous coronary intervention (PCI), to aid in selecting patients with
sufficient life expectancy to benefit from bioabsorbable scaffolds. BACKGROUND:
Clinical trials are currently designed to demonstrate superiority of
bioabsorbable scaffolds over metal devices up to 5 years after implantation.
METHODS: From 2000 to 2011, 19.532 consecutive patients underwent PCI in a
tertiary referral hospital. Patients were randomly (2:1) divided into a training
(N = 13,090) and validation (N = 6,442) set. Cox regression was used to identify
determinants of long-term mortality in the training set and used to develop a
risk model. Model performance was studied in the training and validation dataset.
RESULTS: Median age was 63 years (IQR 54-72) and 72% were men. Median follow-up
was 3.6 years (interquartile range [IQR] 2.4-6.8). The ratio elective vs. non
elective PCIs was 42/58. During 88,620 patient-years of follow-up, 3,156 deaths
occurred, implying an incidence rate of 35.6 per 1,000. Estimated 5-year
mortality was 12.9%.Regression analysis revealed age, body mass index, diabetes
mellitus, renal insufficiency, prior myocardial infarction, PCI indication,
lesion location, number of diseased vessels and cardiogenic shock at presentation
as determinants of mortality. The long-term risk model showed good discrimination
in the training and validation sets (c-indices 0.76 and 0.74), whereas
calibration was appropriate. CONCLUSIONS: A simple risk model, containing 9
baseline clinical and angiographic variables effectively predicts long-term
mortality after PCI and may possibly be used to select suitable patients for
bioabsorbable scaffolds.
PMID- 28707321
TI - Expansion of BCR/ABL1+ cells requires PAK2 but not PAK1.
AB - The p21-activated kinases (PAKs) are key nodes in oncogenic signalling pathways
controlling growth, survival, and motility of cancer cells. Their activity is
increased in many human cancers and is associated with poor prognosis. To date,
PAK deregulation has mainly been studied in solid tumours, where PAK1 and PAK4
are the main isoforms deregulated. We show that PAK1 and PAK2 are the critical
isoforms in a BCR/ABL1+ haematopoietic malignancy. In suspension, leukaemic cells
deficient for PAK1 and PAK2 undergo apoptosis, while the loss of either protein
is well tolerated. Transfer of medium conditioned by shPAK2- but not shPAK1
expressing leukaemic cells interferes with endothelial cell growth. We found that
leukaemic cells produce exosomes containing PAK2. Transfer of isolated exosomes
supports endothelial cell proliferation. In parallel, we found that leukaemic
cells explicitly require PAK2 to grow towards an extracellular matrix. PAK2
deficient cells fail to form colonies in methylcellulose and to induce lymphomas
in vivo. PAK2 might therefore be the critical isoform in leukaemic cells by
controlling tumour growth in a dual manner: vascularization via exosome-mediated
transfer to endothelial cells and remodelling of the extracellular matrix. This
finding suggests that the PAK2 isoform represents a promising target for the
treatment of haematological diseases.
PMID- 28707323
TI - Exogenous application of IAA alleviates effects of supplemental ultraviolet-B
radiation in the medicinal plant Withania somnifera Dunal.
AB - Supplemental (s)-UV-B radiation has adverse effects on the majority of plants.
The present study was conducted to evaluate the effects of exogenous application
of the growth hormone indole acetic acid (IAA) on various morphological,
physiological and biochemical characteristics of Withania somnifera, an
indigenous medicinal plant, subjected to s-UV-B. The s-UV-B-treated plants
received ambient + 3.6 kJm-2 .day-1 biologically effective UV-B, and IAA was
applied at two doses (200 and 400 ppm) to s-UV-B-exposed plants. The plant was
forced to compromise its growth, development and photosynthetic patterns to
survive under s-UV-B by increasing concentrations of secondary metabolites and
antioxidants (thiol, proline, ascorbic acid, alpha-tocopherol, ascorbate
peroxidase, catalase, glutathione reductase, peroxidase, polyphenol oxidase,
superoxide dismutase) to counteract oxidative stress. Increases in secondary
metabolites were evidenced as increased activity of phenylpropanoid pathway
enzymes: phenylalanine ammonia lyase, cinnamyl alcohol dehydrogenase, 4-coumarate
CoA ligase, chalcone isomerase and dihydroflavonol reductase. Application of
different IAA doses reversed the detrimental effects of s-UV-B on W. somnifera by
improving growth and photosynthesis and reducing concentrations of secondary
metabolites and non-enzymatic antioxidants. Antioxidant enzymes, however, had a
synergistic effect on s-UV-B treatment and IAA application. The effects of s-UV-B
on W. somnifera are ameliorated to varying degrees upon exogenous IAA
application, and synergistic enhancement of antioxidant enzymes under s-UV-B+IAA
treatment might be responsible for the partial recuperation of growth and plant
protein content, as a UV-B-exposed plant is forced to allocate most of its
photosynthate towards production of enzymes related to antioxidant defence.
PMID- 28707324
TI - High concordance between clinical diagnosis of epidermolysis bullosa and
immunofluorescence with a small, well-matched antibody panel.
PMID- 28707325
TI - Effects of scalp nerve block on pain and emergence agitation after paediatric
nevus surgery: a clinical trial.
AB - BACKGROUND: Pain is considered as being one cause of post-operative emergence
agitation (EA) from sevoflurane anaesthesia. The purpose of this study was to
investigate the pure effect of post-operative pain on EA after sevoflurane
anaesthesia in preschool children undergoing excision of scalp nevi. METHODS:
Forty-four children, 1-7 years old, undergoing scalp nevus excision were
enrolled. Patients were randomly assigned to two groups: the remifentanil group
received single intravenous injection of short-acting synthetic opioid,
remifentanil 1 MUg/kg just before the scalp incision, and the block group
received scalp nerve block with 0.25% ropivacaine after intubation. The end-tidal
sevoflurane concentration was maintained around 1.5 vol% unless the mean arterial
pressure is out of +/-20% range of preoperative values during surgery in both
groups. Watcha behaviour scale for EA and face, legs, activity, cry,
consolability (FLACC) scale scores for pain were recorded post-operatively.
RESULTS: There was no difference in end-tidal sevoflurane concentration between
the two groups during surgery and the emergence period. Agitation incidence and
scores were not different between the two groups during the recovery period.
FLACC scale was significantly lower in the block group than in the remifentanil
group at post-anaesthesia care unit (PACU) arrival, at 10 and 20 min after PACU
arrival, respectively. CONCLUSION: The scalp nerve block decreased the early post
operative pain after paediatric nevus excision, but it did not decrease the
incidence of EA with sevoflurane anaesthesia.
PMID- 28707326
TI - Perineural invasion present exclusively in central tissue blocks of Mohs surgical
excisions of basal cell carcinoma.
AB - Perineural invasion (PNI) may be present in basal cell carcinomas (BCC) treated
with Mohs micrographic surgery. This single-centre, non-randomised, prospective
study demonstrates the potential for PNI to exist exclusively within the central
tissue blocks of Mohs specimens.
PMID- 28707327
TI - Environmental drivers of coral reef carbonate production and bioerosion: a multi
scale analysis.
AB - The resilience of coral reefs depends on the balance between reef growth and reef
breakdown, and their responses to changing environmental conditions. Across the
2500-km Hawaiian Archipelago, we quantified rates of carbonate production,
bioerosion, and net accretion at regional, island, site, and within-site spatial
scales and tested how these rates respond to environmental conditions across
different spatial scales. Overall, there were four major outcomes from this
study: (1) bioerosion rates were generally higher in the populated Main Hawaiian
Islands (MHI) than the remote, protected Northwestern Hawaiian Islands (NWHI),
while carbonate production rates did not vary significantly between the two
regions; (2) variability in carbonate production, bioerosion, and net accretion
rates was greatest at the smallest within-reef spatial scale; (3) carbonate
production and bioerosion rates were associated with distinct sets of
environmental parameters; and (4) the strongest correlates of carbonate
production, bioerosion, and net accretion rates were different between the MHI
region and the NWHI region: in the MHI, the dominant correlates were percent
cover of macroalgae and herbivorous fish biomass for carbonate production and
bioerosion, respectively, whereas in the NWHI, the top correlates were total
alkalinity and benthic cover. This study highlights the need to understand
accretion and erosion processes as well as local environmental conditions to
predict net coral reef responses to future environmental changes.
PMID- 28707328
TI - Antecedents of transition patterns of depressive symptom trajectories from
adolescence to young adulthood.
AB - This study examined (a) transition patterns from adolescent-specific depressive
symptom trajectory classes to young adult-specific trajectory classes (N = 537;
15-26 years) and (b) identified risk factors associated with these transition
patterns. The latent classes and transition analyses identified three
transitional patterns of depressive symptom trajectories, including a
deteriorating pattern (8.2%), a recovering pattern (22.5%), and a consistently
low pattern (69.3%). Additionally, the results showed that contextual risk
factors (i.e., negative economic events, negative romantic relationships, and low
college enrolment rates) in the transition period to young adulthood were more
positively associated with deteriorated or recovered transition patterns of
depressive symptom trajectories than with the consistently low transition
patterns even after taking into account the effects of adolescent risk factors.
The identification of dynamic transition patterns in depressive symptom
trajectories from adolescence to young adulthood and risk factors provide useful
tools for preventive and intervention efforts. Statement of contribution What is
already known on this subject? Heterogeneous trajectories of depressive symptoms
across adolescence and young adulthood have been reported. Psychosocial
characteristics differentiate trajectories of depressive symptoms from
adolescence to young adulthood. What does this study add? Dynamic transition
patterns of depressive symptom trajectories are found between adolescence and
young adulthood. Life experiences in the transition period are uniquely
associated with the transition patterns of depressive symptom trajectories even
after adjusting the effects of adolescent characteristics.
PMID- 28707329
TI - Drugs and obstructive sleep apnoea.
PMID- 28707330
TI - The impact of dialysis modality and membrane characteristics on intradialytic
hypotension.
AB - The risk of intradialytic hypotension (IDH) is determined by various factors,
among them dialysis modality and dialyzer membrane. We conducted a literature
search in PubMed on November 1, 2016 and selected relevant randomized controlled
and cross-over trials, and prospective and retrospective cohort studies published
in English that investigated the association between IDH and dialysis modality
and membrane, respectively. This literature search revealed 669 publications on
dialysis modality, 64 on dialysis membrane, and 24 on acetate/bicarbonate
dialysate. After omission of duplicate papers and publications outside the scope
of this review, we selected 34 papers for inclusion, 19 on dialysis modality, 8
on dialyzer membrane, and 7 on acetate/bicarbonate dialysate. Several strands of
evidence indicate that hemodiafiltration (HDF) is associated with lower IDH rates
compared to hemodialysis (HD). Data do not show an unequivocal benefit of
synthetic vs nonsynthetic dialyzer membranes with respect to IDH occurrence.
Acetate-based vs bicarbonate-based dialysate appears to be associated with an
increased IDH rate.
PMID- 28707331
TI - Epstein-Barr virus lytic cycle involvement in diffuse large B cell lymphoma.
AB - Epstein-Barr virus (EBV)-mediated B cell transformation is achieved predominantly
through the action of latent proteins, but recent evidence suggests that lytic
EBV replication has also a certain pathogenic role in lymphomagenesis, at least
in the early phases of cell transformation. Particularly, in diffuse large B cell
lymphoma (DLBCL), the EBV lytic cycle is by and large unexplored, so to disclose
lytic cell contribution to lymphomagenesis, our aim was to evaluate viral early
and late lytic gene expression in relation to several immune response markers in
a series of EBV+ DLBCL from Argentina. An unexpected number of cells expressed
lytic transcripts, being transcribed at the BZLF1, BHRF1, and BLLF1 locus, by
real-time quantitative polymerase chain reaction. This lytic antigen expression
was confirmed by immunohistochemical staining for BMRF1 early lytic protein, and
a positive correlation between lytic and latent genes was confirmed, revealing a
close link between their expressions in EBV+ DLBCL pathogenesis. Remarkably,
BZLF1 displayed a negative correlation with CD4 cell counts, and this could be in
part justified by the restriction of antigen presentation previously reported.
The direct correlation for the late lytic gene BLLF1 and IFNgamma in this series
could represent a specific response directed towards this antigen. Interleukin 10
transcripts also displayed a positive correlation with lytic expression,
indicating that regulatory mechanisms could be also involved on EBV-associated
DLBCL pathogenesis in our series. Complete lytic reactivation in EBV-positive
tumours could potentially kill EBV-positive malignant cells, providing a tool to
promote tumour cell killing mediated by EBV as a complementary treatment
strategy.
PMID- 28707332
TI - Conjugated Polymer for Voltage-Controlled Release of Molecules.
AB - Conjugated polymers are attractive in numerous biological applications because
they are flexible, biocompatible, cost-effective, solution-processable, and
electronic/ionic conductive. One interesting application is for controllable drug
release, and this has been realized previously using organic electronic ion
pumps. However, organic electronic ion pumps show high operating voltages and
limited transportation efficiency. Here, the first report of low-voltage
controlled molecular release with a novel organic device based on a conjugated
polymer poly(3-hexylthiophene) is presented. The releasing rate of molecules can
be accurately controlled by the duration of the voltage applied on the device.
The use of a handy mobile phone to remotely control the releasing process and its
application in delivering an anticancer drug to treat cancer cells are also
successfully demonstrated. The working mechanism of the device is attributed to
the unique switchable permeability of poly(3-hexylthiophene) in aqueous solutions
under a bias voltage that can tune the wettability of poly(3-hexylthiophene) via
oxidation or reduction processes. The organic devices are expected to find many
promising applications for controllable drug delivery in biological systems.
PMID- 28707333
TI - Equity in maternal- and infant-care services in China: A trend analysis based on
residence and area (2000-2014).
AB - Equity in maternal- and infant-care services is key to achieving equity in
maternal and infant health outcomes. In this study, 12 indicators of maternal and
infant services were selected to measure equity in maternal and infant services
in China from 2000-2014 using the Theil index and between-group variance, with
the result showing that equity has improved steadily and significantly, though
serious inequities in premarital and reproductive health services remain.
Relatively speaking, equity at the interprovincial level has increased, but
equity in urban-rural stratification has improved more, indicating that policies
should focus on interprovincial inequities and premarital and reproductive health
services.
PMID- 28707334
TI - Human Zika and West Nile virus neurological infections.
PMID- 28707335
TI - Hurricane preparedness among elderly residents in South Florida.
AB - OBJECTIVES: The purpose of this study was to describe factors associated with
hurricane preparation and to test a theoretical model of hurricane preparation
decision process among a group of elderly residents living in a high-risk
geographical area. DESIGN AND SAMPLE: This is a descriptive, correlational study.
A convenience sample consisted of 188 English-speaking individuals who were aged
55 years or older. MEASURES: In addition to demographic information, two survey
instruments were used. Theoretical constructs were operationalized through Moon's
Hurricane Preparation Questionnaire. Hurricane preparedness was measured by self
reported responses to FEMA's inventory checklist, which addresses the recommended
basic steps of preparation. RESULTS: The theoretical model of hurricane
preparation decision process was supported. Main barriers to preparation are the
need for cooperation from others and cost of preparation. Participants reported
having taken many preparatory steps to shelter-in-place, but too few are prepared
if their home were storm-damaged or they should have to evacuate. CONCLUSIONS:
Findings are consistent with previous studies of samples drawn from similar
populations. This report provides guidance as to how public health nurses can
become involved with the population and develop interventions based on the
constructs of the theoretical model.
PMID- 28707336
TI - Mechanical role of the spatial patterns of contractile cells in invagination of
growing epithelial tissue.
AB - Epithelial invagination is one of the fundamental deformation modes during
morphogenesis, and is essential for deriving the three-dimensional shapes of
organs from a flat epithelial sheet. Invagination occurs in an orderly manner
according to the spatial pattern of the contractile cells; however, it remains
elusive how tissue deformation can be caused by cellular activity in the
patterned region. In this study, we investigated the mechanical role of the
spatial patterns of the contractile cells in invagination of growing tissue using
multicellular dynamics simulations. We found that cell proliferation and apical
constriction were responsible for expanding the degree of tissue deformation and
determining the location of the deformation, respectively. The direction of
invagination depended on the spatial pattern of the contractile cells. Further,
comparing the simulation results of surface and line contractions as possible
modes of apical constriction, we found that the direction of invagination
differed between these two modes even if the spatial pattern was the same. These
results indicate that the buckling of the epithelial cell sheet caused by cell
proliferation causes the invagination, with the direction and location determined
by the configuration of the wedge-shaped cells given by the spatial pattern of
the contractile cells.
PMID- 28707337
TI - Systematic review with meta-analysis: the efficacy of faecal microbiota
transplantation for the treatment of recurrent and refractory Clostridium
difficile infection.
AB - BACKGROUND: Clostridium difficile infection (CDI) is the commonest nosocomial
cause of diarrhoea. Faecal microbiota transplantation (FMT) is an approved
treatment for recurrent or refractory CDI but there is uncertainty about its use.
AIM: To evaluate the efficacy of FMT in treating recurrent and refractory CDI and
investigate outcomes from modes of delivery and preparation. METHODS: A
systematic review and meta-analysis was performed. MEDLINE, EMBASE, CINAHL,
Cochrane Library, trial registers and conference proceedings were searched.
Studies on FMT in recurrent and refractory CDI were included. The primary outcome
was clinical resolution with subgroup analyses of modes of delivery and
preparation. Random effects meta-analyses were used to combine data. RESULTS:
Thirty seven studies were included; seven randomised controlled trials and 30
case series. FMT was more effective than vancomycin (RR: 0.23 95%CI 0.07-0.80) in
resolving recurrent and refractory CDI. Clinical resolution across all studies
was 92% (95%CI 89%-94%). A significant difference was observed between lower GI
and upper GI delivery of FMT 95% (95%CI 92%-97%) vs 88% (95%CI 82%-94%)
respectively (P=.02). There was no difference between fresh and frozen FMT 92%
(95%CI 89%-95%) vs 93% (95%CI 87%-97%) respectively (P=.84). Administering
consecutive courses of FMT following failure of first FMT resulted in an
incremental effect. Donor screening was consistent but variability existed in
recipient preparation and volume of FMT. Serious adverse events were uncommon.
CONCLUSION: Faecal microbiota transplantation is an effective treatment for
recurrent and refractory Clostridium difficile infection, independent of
preparation and route of delivery.
PMID- 28707338
TI - Evaluation of interthalamic adhesion size as an indicator of brain atrophy in
dogs with and without cognitive dysfunction.
AB - Interthalamic adhesion thickness has been previously described as a parameter for
quantifying canine brain atrophy and hypothesized to correlate with brain height
or ventricular size. However, studies testing this hypothesis are lacking. This
retrospective cross-sectional study aimed to compare interthalamic adhesion
thickness, interthalamic adhesion thickness/brain height ratio, and interthalamic
adhesion thickness/brain height ratio/lateral ventricle to brain height ratio
values in dogs with and without cognitive dysfunction. Medical records for dogs
meeting the following inclusion criteria were retrieved from two hospitals:
available brain magnetic resonance imaging (MRI) or computed tomography (CT)
studies, no cerebral parenchymal lesions, and no prior neurological treatment.
For each included dog, values of interthalamic adhesion thickness, interthalamic
adhesion thickness/brain height ratio, and interthalamic adhesion thickness/brain
height ratio/lateral ventricle to brain height ratio were measured by one
observer from transverse CT or MRI images and a consensus was reached. A total of
113 dogs met inclusion criteria. Dogs were divided into three groups based on the
following criteria: Young group (no cognitive dysfunction, <9-year-old, n = 43),
Aging group (no cognitive dysfunction, >=9-year-old, n = 61), and Dementia group
(n = 9). All three parameters were significantly lower in the dementia group than
in the Young and Aging groups. In the Young and Aging groups, there was
significant negative correlation of all three parameters with age and positive
correlation of interthalamic adhesion thickness and interthalamic adhesion
thickness/brain height ratio/lateral ventricle to brain height ratio with body
weight, while there was no correlation of interthalamic adhesion thickness/brain
height ratio with body weight (P < 0.05). There were no differences in all three
parameters according to skull type or gender. Findings from the current study
supported the use of interthalamic adhesion thickness, interthalamic adhesion
thickness/brain height ratio, and interthalamic adhesion thickness/brain height
ratio/lateral ventricle to brain height ratio for quantifying brain atrophy in
dogs with cognitive dysfunction.
PMID- 28707339
TI - Neutron structure of the T26H mutant of T4 phage lysozyme provides insight into
the catalytic activity of the mutant enzyme and how it differs from that of wild
type.
AB - T4 phage lysozyme is an inverting glycoside hydrolase that degrades the murein of
bacterial cell walls by cleaving the beta-1,4-glycosidic bond. The substitution
of the catalytic Thr26 residue to a histidine converts the wild type from an
inverting to a retaining enzyme, which implies that the original general acid
Glu11 can also act as an acid/base catalyst in the hydrolysis. Here, we have
determined the neutron structure of the perdeuterated T26H mutant to clarify the
protonation states of Glu11 and the substituted His26, which are key in the
retaining reaction. The 2.09-A resolution structure shows that the imidazole
group of His26 is in its singly protonated form in the active site, suggesting
that the deprotonated NE2 atom of His26 can attack the anomeric carbon of bound
substrate as a nucleophile. The carboxyl group of Glu11 is partially protonated
and interacts with the unusual neutral state of the guanidine moiety of Arg145,
as well as two heavy water molecules. Considering that one of the water-binding
sites has the potential to be occupied by a hydronium ion, the bulk solvent could
be the source for the protonation of Glu11. The respective protonation states of
Glu11 and His26 are consistent with the bond lengths determined by an
unrestrained refinement of the high-resolution X-ray structure of T26H at 1.04-A
resolution. The detail structural information, including the coordinates of the
deuterium atoms in the active site, provides insight into the distinctively
different catalytic activities of the mutant and wild type enzymes.
PMID- 28707340
TI - Removal of a consensus proline is not sufficient to allow tetratricopeptide
repeat oligomerization.
AB - Tetratricopeptide repeat (TPR) domains are ubiquitous protein interaction domains
that adopt a modular antiparallel array of alpha-helices. The TPR fold typically
adopts a monomeric state, and consensus TPRs sequences successfully fold into the
expected monomeric topology. The versatility of the TPR fold also supports
different quaternary structures, which may function as regulatory switches. One
example is yeast mitochondrial fission 1 (Fis1) that appears to interconvert
between monomer and dimer states in regulating division of peroxisomes and
mitochondria. Whether human Fis1 can also interconvert like the yeast molecule is
unknown. A TPR consensus proline residue present in human Fis1 is absent in the
yeast molecule and, when added, prevents yeast Fis1 dimerization suggesting that
the TPR consensus proline might have persisted to prevent TPR oligomerization.
Here, we address this question with human Fis1 and the consensus TPR protein
CTPR3. We demonstrate that human Fis1 does not form a noncovalent dimer via its
TPR domain, despite conditions that favor dimerization of the yeast protein. We
also show that the presence of the consensus proline is not sufficient to forbid
TPR dimerization. Lastly, an analysis of all available TPR protein structures (22
nonredundant structures, totaling 64 TPRs-42 with the consensus proline and 22
without) revealed that the consensus proline is not necessary for turn formation,
but does favor shorter turns. This work suggests the TPR consensus proline is not
to prevent oligomerization, but to favor tight turns between repeats.
PMID- 28707341
TI - Impact of Hyperkalemia and Worsening Renal Function on the Use of Renin
Angiotensin Aldosterone System Inhibitors in Chronic Heart Failure With Reduced
Ejection Fraction.
AB - Patients with heart failure (HF) and reduced ejection fraction (HFREF) are at
increased risk of death and hospitalizations for HF. Numerous registries have
reported a large and persistent gap between real-life practice in the use of life
saving evidence-based therapies, such as renin angiotensin system inhibitors,
beta blockers, mineralocorticoid receptor antagonists (MRAs), and recommended
practices in international guidelines. The fears of inducing hyperkalemia and/or
worsening renal function are the main triggers of this underuse.
PMID- 28707342
TI - Ratio of ellipticities between 192 and 208 nm (R1 ): An effective electronic
circular dichroism parameter for characterization of the helical components of
proteins and peptides.
AB - Circular dichroism (CD) spectroscopy represents an important tool for
characterization of the peptide and protein secondary structures that mainly
arise from the conformational disposition of the peptide backbone in solution. In
1991 Manning and Woody proposed that, in addition to the signal intensity, the
ratio between [theta]npi* and [theta]pipi*|| ((R2 ) ? [theta]222 /[theta]208 ),
along with [theta]pipi*? and [theta]pipi*|| ((R1 ) ? [theta]192 /[theta]208 ),
may be utilized towards identifying the peptide/protein conformation (especially
310 - and alpha-helices). However, till date the use of the ratiometric
ellipticity component for helical structure analysis of peptides and proteins has
not been reported. We studied a series of temperature dependent CD spectra of a
thermally stable, model helical peptide and its related analogs in water as a
function of added 2,2,2-trifluoroethanol (TFE) in order to explore their
landscape of helicity. For the first time, we have experimentally shown here that
the R1 parameter can characterize better the individual helices, while the other
parameter R2 and the signal intensity do not always converge. We emphasize the
use of the R1 ratio of ellipticities for helical characterization because of the
common origin of these two bands (exciton splitting of the amide pi-> pi*
transition in a helical polypeptide). This approach may become worthwhile and
timely with the increasing accessibility of CD synchrotron sources.
PMID- 28707343
TI - Peroral endoscopic myotomy is safe and effective in achalasia patients aged older
than 60 years compared with younger patients.
AB - AIM: Peroral endoscopic myotomy (POEM) has been proven to be effective for
treating achalasia, but there are limited data on POEM in elderly patients. We
therefore aimed to assess the role of POEM for achalasia in patients aged >=60
years. METHODS: All consecutive patients that underwent POEM between December
2011 and November 2015 at a single center were retrospectively reviewed. Patients
aged >=60 years were assigned to group A, whereas patients aged <60 years were
assigned to group B. Demographic data, clinical data and treatment outcomes were
compared between the two groups. RESULTS: During the study period, 113 patients
(18 in group A, and 95 in group B) were enrolled. The mean age of patients in
group A was 63 +/- 3.9 years (range 60-74 years; 55.6% women), and that for
patients in group B was 37.7 +/- 11.6 years (range 18-59 years; 42.2% women). The
procedural time in group A was similar to group B (66.3 +/- 33.3 vs 59.8 +/- 24.2
min, P = 0.332). There were also no significant differences in the incidence of
intraoperative complications (P = 1.000) and gastroesophageal reflux rate (P =
0.906) between the two groups. During the mean follow-up period of 25.2 months,
treatment success (Eckardt score <=3) was achieved in 92.9% of patients in group
A, and 89.9% in group B (P = 1.000). CONCLUSIONS: As well as in younger patients,
POEM can be safely carried out in elderly patients, providing significant symptom
relief. POEM might be recommended as the first therapeutic approach to elderly
achalasia patients. Geriatr Gerontol Int 2017; 17: 2407-2413.
PMID- 28707344
TI - Detection of viable Helicobacter pylori inside free-living amoebae in wastewater
and drinking water samples from Eastern Spain.
AB - Helicobacter pylori is one of the most concerning emerging waterborne pathogens.
It has been suggested that it could survive in water inside free-living amoebae
(FLA), but nobody has studied this relationship in the environment yet. Thus, we
aimed to detect viable H. pylori cells from inside FLA in water samples. Sixty
nine wastewater and 31 drinking water samples were collected. FLA were purified
and identified by PCR and sequencing. For exclusively detecting H. pylori inside
FLA, samples were exposed to sodium hypochlorite and assayed by specific PMA
qPCR, DVC-FISH and culture. FLA were detected in 38.7% of drinking water and
79.7% of wastewater samples, even after disinfection. In wastewater, Acanthamoeba
spp. and members of the family Vahlkampfiidae were identified. In drinking water,
Acanthamoeba spp. and Echinamoeba and/or Vermamoeba were present. In 39 (58.2%)
FLA-positive samples, H. pylori was detected by PMA-qPCR. After DVC-FISH, 21
(31.3%) samples harboured viable H. pylori internalized cells. H. pylori was
cultured from 10 wastewater samples. To our knowledge, this is the first report
that demonstrates that H. pylori can survive inside FLA in drinking water and
wastewater, strongly supporting the hypothesis that FLA could play an important
role in the transmission of H. pylori to humans.
PMID- 28707345
TI - The cascade of care to prevent mother-to-child transmission in Rio de Janeiro,
Brazil, 1996-2013: improving but still some way to go.
AB - OBJECTIVE: To describe the cascade of care to HIV mother-to-child transmission
(PMTCT) in a Rio de Janeiro reference paediatric clinic and evaluate the main
factors possibly associated with HIV transmission. METHODS: Data on antenatal
care (ANC), perinatal and neonatal assistance to HIV-infected and HIV-exposed but
uninfected children assisted in the clinic from 1996 to 2013 were collected. The
cascade of care was graphically demonstrated, and possible factors associated
with HIV infection were described using regression models for bivariate and
multivariate analysis. We imputed missing values of explanatory variables for the
final model. RESULTS: A total of 989 children were included in the analysis: 211
were HIV and 778 HEU. Graphically, the HIV PMTCT cascade of care improved from
1996/2000 to the later periods, but not from 2001/2006 to 2007/2013. The main
factor independently associated with the HIV infection over time was
breastfeeding. In the period 1996/2000, the lack of antiretroviral use during
labour was associated HIV transmission. While in 2001/2007, other modes of
delivery but elective Caesarean section, and lack of maternal antiretroviral use
during ANC were associated with HIV transmission. In the last period, the main
factor associated with transmission was the lack of maternal ANC. CONCLUSIONS:
The HIV PMTCT cascade improved over time, but HIV vertical transmission remains a
problem, and better access to ANC is needed.
PMID- 28707346
TI - Relationship between response rates and median progression-free survival in non
Hodgkin's lymphoma: A meta-analysis of published clinical trials.
AB - Demonstration of clinical effectiveness of a non-Hodgkin's lymphoma (NHL)
treatment generally involves determination of progression-free survival (PFS).
However, the long evaluation time of PFS limits its utility to make timely
decisions in drug development. Therefore, the objective of this analysis was to
determine the relationship between response rates and median PFS in NHL. A
database was systematically developed from 513 identified NHL trials reported
from 1996 to 2015. Potential predictors of the relationship between response
rates and PFS were evaluated, including age, sex, treatment, percentage of
treatment-naive patients, and subtype of NHL. Seventy-three trials involving 86
cohorts were included in the meta-analysis. Linear regression analysis using
logit of response rates and logarithm of median PFS indicated that the
correlation between overall response rate (ORR) and median PFS was higher (R2 =
0.70) when compared to that of complete response (CR) rate and median PFS (R2 =
0.57). Furthermore, the correlation was improved with the addition of percentage
of treatment-naive patients and percentage of patients with follicular lymphoma
(FL) (P < .005) between ORR and median PFS (R2 = 0.78), and between CR rate and
median PFS relationship (R2 = 0.74). Treatment was not found to alter this
relationship. In summary, ORR is as good as CR rate in predicting median PFS.
Moreover, longer median PFS is expected in the trials including treatment-naive
and/or FL patients at a given ORR/CR rate. The determined relationship can be
used to project the median PFS based on ORR or CR rate.
PMID- 28707347
TI - Interspecific variation in the tetradactyl manus of modern tapirs
(Perissodactyla: Tapirus) exposed using geometric morphometrics.
AB - The distal forelimb (autopodium) of quadrupedal mammals is a key morphological
unit involved in locomotion, body support, and interaction with the substrate.
The manus of the tapir (Perissodactyla: Tapirus) is unique within modern
perissodactyls, as it retains the plesiomorphic tetradactyl (four-toed) condition
also exhibited by basal equids and rhinoceroses. Tapirs are known to exhibit
anatomical mesaxonic symmetry in the manus, although interspecific differences
and biomechanical mesaxony have yet to be rigorously tested. Here, we investigate
variation in the manus morphology of four modern tapir species (Tapirus indicus,
Tapirus bairdii, Tapirus pinchaque, and Tapirus terrestris) using a geometric
morphometric approach. Autopodial bones were laser scanned to capture surface
shape and morphology was quantified using 3D-landmark analysis. Landmarks were
aligned using Generalised Procrustes Analysis, with discriminant function and
partial least square analyses performed on aligned coordinate data to identify
features that significantly separate tapir species. Overall, our results support
the previously held hypothesis that T. indicus is morphologically separate from
neotropical tapirs; however, previous conclusions regarding function from
morphological differences are shown to require reassessment. We find evidence
indicating that T. bairdii exhibits reduced reliance on the lateral fifth digit
compared to other tapirs. Morphometric assessment of the metacarpophalangeal
joint and the morphology of the distal facets of the lunate lend evidence toward
high loading on the lateral digits of both the large T. indicus (large body mass)
and the small, long limbed T. pinchaque (ground impact). Our results support
other recent studies on T. pinchaque, suggesting subtle but important adaptations
to a compliant but inclined habitat. In conclusion, we demonstrate further
evidence that the modern tapir forelimb is a variable locomotor unit with a range
of interspecific features tailored to habitual and biomechanical needs of each
species.
PMID- 28707348
TI - Regulation of cell arrangement using a novel composite micropattern.
AB - Micropatterning technique has been used to control single cell geometry in many
researches, however, this is no report that it is used to control multicelluar
geometry, which not only control single cell geometry but also organize those
cells by a certain pattern. In this work, a composite protein micropattern is
developed to control both cell shape and cell location simultaneously. The
composite micropattern consists of a central circle 15 MUm in diameter for single
cell capture, surrounded by small, square arrays (3 MUm * 3 MUm) for cell
spreading. This is surrounded by a border 2 MUm wide for restricting cell edges.
The composite pattern results in two-cell and three-cell capture efficiencies of
32.1% +/- 1.94% and 24.2% +/- 2.89%, respectively, representing an 8.52% and
9.58% increase, respectively, over rates of original patterns. Fluorescent
imaging of cytoskeleton alignment demonstrates that actin is gradually aligned
parallel to the direction of the entire pattern arrangement, rather than to that
of a single pattern. This indicates that cell arrangement is also an important
factor in determining cell physiology. This composite micropattern could be a
potential method to precisely control multi-cells for cell junctions, cell
interactions, cell signal transduction, and eventually for tissue rebuilding
study. (c) 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 3093
3101, 2017.
PMID- 28707349
TI - Assessment of bioresorbable scaffold with a novel high-definition 60 MHz IVUS
imaging system: Comparison with 40-MHz IVUS referenced to optical coherence
tomography.
AB - BACKGROUND: In vivo assessment of bioresorbable scaffold (BRS) is of growing
clinical interest. The novel 60MHz high-definition intravascular ultrasound (HD
IVUS) has been developed to overcome the limitations of conventional 40 MHz IVUS.
This study aimed to evaluate the performance and limitations of 60 MHz HD-IVUS
compared with 40 MHz IVUS with respect to polymeric-strut visualization,
quantitative and qualitative analysis, and feasibility of high-speed pullback in
the assessment of BRS. METHODS AND RESULTS: In a bench-test model, 361 struts
were analyzed to evaluate the influence of ultrasound-beam angles and proximity
of adjacent struts on IVUS visualization of BRS struts. Various settings were
created by deforming the BRS and positioning the transducer offcenter. In an in
vivo swine coronary model, scaffold and lumen areas, degree of visible external
elastic membrane, incomplete strut apposition, and strut fracture were evaluated
in 59 matched cross-sections obtained at conventional (0.5 mm/sec) and high speed
(10 mm/sec) pullbacks. Both studies utilized optical coherence tomography (OCT)
as reference. Overall, 60 MHz HD-IVUS demonstrated significantly improved
visualization of polymeric struts compared with 40 MHz IVUS (well-visualized:
84.5% vs 62.3%, not visible: 4.4% vs 13.9%, respectively. P < 0.001), which was
less affected by the beam angle and adjacent strut proximity. In the in vivo
model, 60-MHz HD-IVUS showed better agreement of area measurements and strut
abnormalities with OCT than 40 MHz IVUS. These findings were also confirmed on
high-speed pullback images of 60 MHz HD-IVUS. CONCLUSION: As referenced to OCT,
this study showed superiority of 60 MHz HD-IVUS over 40 MHz IVUS in the
assessment of BRS with feasibility of high-speed pullback imaging.
PMID- 28707350
TI - Midterm to long-term safety and efficacy of self-expandable nitinol stent
implantation for coarctation of aorta in adults.
AB - PURPOSE: Endovascular treatment of coarctation of aorta (CoA) by self-expandable
Nitinol stents is one of the recognized treatment methods and may be an
alternative to surgery or balloon-expandable stent implantation for CoA but there
is little information about midterm to long term results of self-expandable
stents. METHODS: Sixty-two patients with CoA (40 men), with a mean age of 30.7 +/
11 years, (range 17-63 years) underwent stent implantation with Optimed self
expandable Nitinol stents between 2005 and 2014. Successful outcome was defined
as peak systolic pressure gradient <=20 mmHg after stent implantation. The
patients were followed-up clinically and by echocardiography and in patients, in
whom there was suspicion of recoarctation, CT angiography or recatheterization
was performed. RESULTS: 65 stents were successfully implanted in all 62 patients.
Peak systolic pressure gradient decreased from mean 62.4 +/- 18 mmHg (range 35
100 mmHg) to mean 2.8 +/- 5 mmHg (range 0-15 mmHg; P < 0.001). Stent displacement
occurred in 3 patients during the procedure. These were managed successfully by
an overlapping second stent. None of the patients had major complications such as
aortic dissection, rupture, or vascular access problems. In follow up, only three
patients had recoarctation, and two of these were managed successfully by balloon
redilation or further stenting 16 and 18 months after the first procedure and one
patient refused reintervention. There were two deaths, unrelated to the
procedure, 12 and 78 months after the initial intervention. Follow-up of a mean
of 45.5 +/- 17 months (range 12-105 months) demonstrated no evidence of aneurysm
formation or stent fracture. CONCLUSIONS: Self-expandable nitinol stents for the
treatment of native and recurrent CoA is safe and has good efficacy with
acceptable midterm to long-term outcome.
PMID- 28707351
TI - Relation between working memory and self-regulation capacities and the level of
social skills acquisition in people with moderate intellectual disability.
AB - BACKGROUND: Social competence deficit is one of the main characteristics of
intellectual disability. The aim of this paper is to determine the influence of
working memory (WM) and self-regulation (SR) on social skills in persons with
moderate intellectual disability (MID). METHOD: The sample included 41
participants with MID, aged 14-21. Memorizing animals and maze tasks were used
for WM assessment. SR skills were assessed by the Behavioral Multitask Batteries.
Social skills were rated by the Socialization subscale from the Adaptive Behavior
Assessment System II, which consists of two parts. RESULTS: Social skills part
could mainly be predicted from SR scores (beta = -.441), followed by WM (beta =
.390) and IQ score (beta = .382). Only WM score (beta = .494) had a predictive
value for Leisure time part. CONCLUSION: As WM had a greater influence on social
skills, incorporating WM training into programmes for improving social skills in
persons with MID should be considered.
PMID- 28707352
TI - Hydraulic redistribution: limitations for plants in saline soils.
AB - Hydraulic redistribution (HR), the movement of water from wet to dry patches in
the soil via roots, occurs in different ecosystems and plant species. By
extension of the principle that HR is driven by gradients in soil water
potential, HR has been proposed to occur for plants in saline soils. Despite the
inherent spatial patchiness and salinity gradients in these soils, the lack of
direct evidence of HR in response to osmotic gradients prompted us to ask the
question: are there physical or physiological constraints to HR for plants in
saline environments? We propose that build-up of ions in the root xylem sap and
in the leaf apoplast, with the latter resulting in a large predawn disequilibrium
of water potential in shoots compared with roots and soil, would both impede HR.
We present a conceptual model that illustrates how processes in root systems in
heterogeneous salinity with water potential gradients, even if equal to those in
non-saline soils, will experience a dampened magnitude of water potential
gradients in the soil-plant continuum, minimizing or preventing HR. Finally, we
provide an outlook for understanding the relevance of HR for plants in saline
environments by addressing key research questions on plant salinity tolerance.
PMID- 28707353
TI - Increasing ICA512 autoantibody titers predict development of abnormal oral
glucose tolerance tests.
AB - OBJECTIVE: Determine if autoantibody titer magnitude and variability predict
glucose abnormalities in subjects at risk for type 1 diabetes. RESEARCH DESIGNS
AND METHODS: Demographic information, longitudinal autoantibody titers, and oral
glucose tolerance test (OGTT) data were obtained from the TrialNet Pathway to
Prevention study. Subjects (first and second degree relatives of individuals with
type 1 diabetes) with at least 2 diabetes autoantibodies were selected for
analysis. Autoantibody titer means were calculated for each subject for the
duration of study participation and the relationship between titer tertiles and
glucose value tertiles from OGTTs (normal, impaired, and diabetes) was assessed
with a proportional odds ordinal regression model. A matched pairs analysis was
used to examine the relationship between changes in individual autoantibody
titers and 120-minute glucose values. Titer variability was quantified using
cumulative titer standard deviations. RESULTS: We studied 778 subjects recruited
in the TrialNet Pathway to Prevention study between 2006 and 2014. Increased
cumulative mean titer values for both ICA512 and GAD65 (estimated increase in
proportional odds = 1.61, 95% CI = 1.39, 1.87, P < 1 * 10-9 and 1.17, 95% CI =
1.03, 1.32, P = .016, respectively) were associated with peak 120-minute glucose
values. While fluctuating titer levels were observed in some subjects, no
significant relationship between titer standard deviation and glucose values was
observed. CONCLUSION: ICA512 autoantibody titers associate with progressive
abnormalities in glucose metabolism in subjects at risk for type 1 diabetes.
Fluctuations in autoantibody titers do not correlate with lower rates of
progression to clinical disease.
PMID- 28707354
TI - Additive neurogenesis supported by multiple stem cell populations mediates adult
spinal cord development: A spatiotemporal statistical mapping analysis in a
teleost model of indeterminate growth.
AB - The knifefish Apteronotus leptorhynchus exhibits indeterminate growth throughout
adulthood. This phenomenon extends to the spinal cord, presumably through the
continuous addition of new neurons and glial cells. However, little is known
about the developmental dynamics of cells added during adult growth. The present
work characterizes the structural and functional development of the adult spinal
cord in this model organism through a comprehensive quantitative analysis of the
spatial and temporal dynamics of new cells at various developmental stages. This
analysis, based on a novel statistical mapping approach, revealed within the
adult spinal cord a wide distribution of both mitotically active and quiescent
Sox2-expressing stem/progenitor cells (SPCs). While such cells are particularly
concentrated within the ependymal layer near the central canal, the majority of
them reside in the parenchyma, resembling the distribution of SPCs observed in
the mammalian spinal cord. The active SPCs in the adult knifefish spinal cord
give rise to transit amplifying progenitor cells that undergo a few additional
mitotic divisions before developing into Hu C/D+ neurons and S100+ glial cells.
There is no evidence of long-distance migration of the newborn cells. The
persistence of cell proliferation and differentiation, combined with low levels
of apoptosis, leads to a continuous addition of cells to the existing tissue.
Newly generated neurons have functional and behavioral relevance, as indicated by
the integration of axons of new electromotor neurons into the electric organ of
these weakly electric fish. This results in a gradual increase in the amplitude
of the electric organ discharge during adult development. (c) 2017 Wiley
Periodicals, Inc. Develop Neurobiol 77: 1269-1307, 2017.
PMID- 28707355
TI - Supercritical CO2 Extraction of Lavandula angustifolia Mill. Flowers:
Optimisation of Oxygenated Monoterpenes, Coumarin and Herniarin Content.
AB - INTRODUCTION: Lavandula angustifolia is good source of oxygenated monoterpenes
containing coumarins as well, which are all soluble in supercritical CO2 (SC-CO2
). OBJECTIVE: The study objective is to investigate SC-CO2 extraction parameters
on: the total yield; GC-MS profile of the extracts; relative content of
oxygenated monoterpenes; the amount of coumarin and herniarin; and to determine
optimal SC-CO2 extraction conditions by response surface methodology (RSM).
METHODOLOGY: SC-CO2 extraction was performed under different pressure,
temperature and CO2 flow rate determined by Box-Behnken design (BBD). The sample
mass and the extraction time were kept constant. The chemical profiles and
relative content of oxygenated monoterpenes (as coumarin equivalents, CE) were
determined by GC-MS. Coumarin and herniarin concentrations were dosed by HPLC.
RESULTS: SC-CO2 extracts contained linalool (57.4-217.9 mg CE/100 g), camphor
(10.6-154.4 mg CE/100 g), borneol (6.2-99.9 mg CE/100 g), 1,8-cineole (5.0-70.4
mg CE/100 g), linalyl acetate (86.1-267.9 mg CE/100 g), coumarin (0.95-18.16
mg/100 g), and herniarin (0.95-13.63 mg/100 g). The interaction between the
pressure and CO2 flow rate as well as between the temperature and CO2 flow rate
showed statistically significant influence on the extraction yield. Applying BBD,
the optimum extraction conditions for higher monoterpenes and lower coumarin
content were at 10 MPa, 41 degrees C and CO2 flow rate 2.3 kg/h, and at 30 MPa,
50 degrees C and CO2 flow rate 3 kg/h for higher monoterpenes and coumarin
content. CONCLUSION: SC-CO2 extraction is a viable technique for obtaining
lavender extracts with desirable flavour components. The second-order model based
on BBD predicts the results for SC-CO2 extraction quite satisfactorily. Copyright
(c) 2017 John Wiley & Sons, Ltd.
PMID- 28707356
TI - Intraoperative dermoscopic patterns of subungual squamous cell carcinoma: A case
report.
PMID- 28707357
TI - Supporting a friend, housemate or partner with mental health difficulties: The
student experience.
AB - AIMS: When experiencing mental health difficulties, university students turn to
their friends for support. This study assessed the consequences of caregiving
among a university sample, identifying predictors of caregiving burden among
students. METHODS: A total of 79 students with experience of supporting a friend
with mental health difficulties were recruited through a UK student mental health
charity to complete an online survey. Alongside qualitative data, the online
survey used the Experience of Caregiving Inventory and the Involvement Evaluation
Questionnaire as measures of the consequences of caregiving. RESULTS: Students
supporting friends, housemates or partners were found to experience significant
consequences of caregiving. Frequency of face-to-face contact and duration of
illness predicted more negative consequences of caregiving, but these
relationships were not straightforward. The presence and intensity of
professional support did not influence the experience of caregiving. CONCLUSIONS:
The study suggests that the impact of supporting friends with mental health
difficulties is not insubstantial for students. Broadening the network of
informal social support may help improve the experience for students supporting a
friend, but currently, contact with professional services appears to have a
limited effect.
PMID- 28707358
TI - Suppressed oligodendrocyte steroidogenesis in multiple sclerosis: Implications
for regulation of neuroinflammation.
AB - Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central
nervous system (CNS). Neurosteroids are reported to exert anti-inflammatory
effects in several neurological disorders. We investigated the expression and
actions of the neurosteroid, dehydroepiandrosterone (DHEA), and its more stable
3beta-sulphated ester, DHEA-S, in MS and associated experimental models. CNS
tissues from patients with MS and animals with experimental autoimmune
encephalomyelitis (EAE) displayed reduced DHEA concentrations, accompanied by
diminished expression of the DHEA-synthesizing enzyme CYP17A1 in oligodendrocytes
(ODCs), in association with increased expression of inflammatory genes including
interferon (IFN)-gamma and interleukin (IL)-1beta. CYP17A1 was expressed variably
in different human neural cell types but IFN-gamma exposure selectively reduced
CYP17A1 detection in ODCs. DHEA-S treatment reduced IL-1beta and -6 release from
activated human myeloid cells with minimal effect on lymphocyte viability.
Animals with EAE receiving DHEA-S treatment showed reduced Il1b and Ifng
transcript levels in spinal cord compared to vehicle-treated animals with EAE.
DHEA-S treatment also preserved myelin basic protein immunoreactivity and reduced
axonal loss in animals with EAE, relative to vehicle-treated EAE animals.
Neurobehavioral deficits were reduced in DHEA-S-treated EAE animals compared with
vehicle-treated animals with EAE. Thus, CYP17A1 expression in ODCs and its
product DHEA were downregulated in the CNS during inflammatory demyelination
while DHEA-S provision suppressed neuroinflammation, demyelination, and axonal
injury that was evident as improved neurobehavioral performance. These findings
indicate that DHEA production is an immunoregulatory pathway within the CNS and
its restoration represents a novel treatment approach for neuroinflammatory
diseases.
PMID- 28707359
TI - The feasibility of using pedometers for self-report of steps and accelerometers
for measuring physical activity in adults with intellectual and developmental
disabilities across an 18-month intervention.
AB - BACKGROUND: Improving physical activity in adults with intellectual and
developmental disabilities (IDDs) is recommended to improve weight loss and
general health. However, in order to determine the success of physical activity
interventions, identification of feasible methods for assessment of physical
activities is necessary. The purpose of this study is to assess the feasibility
of adults with IDD to track daily steps and wear an accelerometer. METHODS:
Overweight/obese adults with mild to moderate IDD followed a diet and physical
activity program for 18 months. All participants were asked to wear a pedometer
and track steps daily by using a pedometer and to provide accelerometer data for
7 days at baseline, 6, 12 and 18 months. Adherence to the pedometer protocol and
plausibility of the number of recorded steps were assessed, and these measures
along with average wear time of the accelerometer were recorded. RESULTS: Data
were collected from 149 participants (36.5 +/- 12.2 years of age, 57% female).
Participants recorded a step value on 81.5% of days across the 18-month study,
with 40.9% of written days classified as plausible. When wearing the
accelerometer, 26.8% of participants met the recommended 4-day/10-h wear time
criterion at baseline, and 22.6, 24.8 and 18.8% met the criterion at 6, 12 and 18
months, respectively. CONCLUSIONS: Adults with IDD will adhere reasonably well to
wearing a pedometer long term, but may be unable to record the step data
accurately. Furthermore, adults with IDD have poor compliance with accelerometer
protocols, and future studies should determine if a shorter wear time protocol
would produce valid data in this population.
PMID- 28707360
TI - Reciprocity in autistic and typically developing children and adolescents with
and without mild intellectual disabilities.
AB - The assessment of autism in individuals with mild intellectual disabilities (MID)
is complicated because of the overlap between autistic traits and intellectual
limitations. Impaired social emotional reciprocity is a core diagnostic criterion
for autism. However, it is unknown whether reciprocal behaviour differs between
MID individuals with or without an autism spectrum disorder (ASD). This study
explored differences in reciprocal behaviour of 35 children and adolescents with
MID (intelligence quotient 50-85): 15 with ASD (ASD-MID) and 20 with typical
development (TD-MID) using the Interactive Drawing Test (IDT). ASD-MID
participants showed a lower quality of reciprocal behaviour compared with TD-MID
participants. The difference in quality of reciprocal behaviour between ASD-MID
and TD-MID participants was not significantly related with Peabody Picture
Vocabulary Test scores and thus not attributable to verbal capacity. The IDT is
likely to reflect the child's inclination to display reciprocal behaviour in
everyday situations, as its scale scores were meaningfully associated with the
level of social cognition assessed with the Social Responsiveness Scale. Thus,
the IDT seems well suited for measuring impairments in reciprocal behaviour in
children and adolescents with MID.
PMID- 28707361
TI - Effect of Climatic Parameters on Acute Urinary Retention Incidence.
AB - OBJECTIVES: We investigated the effect of daily climatic parameters on
spontaneous acute urinary retention (sAUR) and evaluated the risk factors for
refractory/recurrent AUR. METHODS: A total of 4194 patients older than 40 years
were diagnosed with AUR in the emergency department at Gangnam Severance
Hospital, Seoul, from January 2007 to May 2016. To evaluate climatic parameters
at sAUR onset, we included individuals living in the area around the hospital. We
excluded patients with fever, who did not return to the hospital after the AUR
episode or with AUR occurring within 2 weeks following admission for surgery or
chemotherapy. RESULTS: Among 818 patients living in the two districts around the
hospital, winter and October had the highest seasonal and monthly rates of sAUR
development, respectively, and sAUR incidence increased with age. Daily
temperature range and mean wind speed were significant risk factors for sAUR
development. Several daily climatic parameters had seasonal effects on sAUR
incidence. Over a mean follow-up of 0.98 years, 122 patients (14.9%) developed
refractory/recurrent AUR. Transitional zone index (TZI; HR = 1.03; P = 0.002) and
prostate-specific antigen (PSA) at the time of sAUR (HR = 1.01; P = 0.030) were
significant predictors of refractory/recurrent AUR. Benign prostate hyperplasia
medication and transurethral prostatectomy after sAUR were not risk factors for
refractory/recurrent AUR. CONCLUSIONS: Cold temperature provoked sAUR in patients
with higher age and International Prostate Symptom Score. Patients with higher
TZI and PSA level at the time of sAUR had a greater risk of developing
refractory/recurrent AUR.
PMID- 28707362
TI - Left atrial pressure and predictors of survival after percutaneous mitral
paravalvular leak closure.
AB - BACKGROUND: Data on the clinical utility of left atrial (LA) hemodynamic
monitoring during percutaneous mitral interventions are limited. OBJECTIVES: To
evaluate the association between intraprocedural LA pressures during percutaneous
mitral paravalvular leak (PVL) closure and long term survival. METHODS: Patients
who underwent mitral PVL repair with invasive LA pressure monitoring were divided
at baseline to three tertiles based on their mean final LA pressure (<25%; 25
30%; >30% of mean systolic blood pressure). Primary outcome was all-cause
mortality. RESULTS: 134 patients (mean age 68 +/- 12 years) were studied. Over 3
year mean follow-up, 81 (38%) patients died. The cumulative probability of death
at 3 years was significantly higher among patients in the highest LA pressure
tertile (56 +/- 8% vs. 28 +/- 5%, log rank P < 0.001). More than mild residual
mitral regurgitation (MR) by transesophageal echocardiography (TEE) was
associated with a 2.5-fold increased risk of death and patients in the highest LA
pressure tertile had 2.2-fold higher mortality (P < 0.001 and = 0.003
respectively). After adjustment for residual MR by TEE, each 10% acute procedural
reduction in LA pressures was associated with a significant 9% reduced risk of
death (P = 0.023). Multivariate Cox regression with adjustment for multiple
predictors of death showed that patients in lower LA pressure tertiles had 59%
lower mortality (P = 0.003). CONCLUSION: Lower LA pressure following mitral PVL
closure is an independent predictor of improved survival, even after adjustment
for residual MR. LA pressure monitoring may be a useful tool for procedural
guidance during mitral PVL closure.
PMID- 28707363
TI - Equine peripheral dental caries: An epidemiological survey assessing prevalence
and possible risk factors in Western Australian horses.
AB - BACKGROUND: Peripheral dental caries is defined as macroscopic destruction of the
calcified dental tissues and can cause considerable dental pathology and pain. It
appears to occur at a high prevalence in Western Australian horses. At present,
risk factors for the condition are poorly understood, making treatment and
prevention difficult. OBJECTIVES: To assess the prevalence of and potential risk
factors for peripheral caries in Western Australian horses. STUDY DESIGN: Cross
sectional, epidemiological study. METHODS: A survey of 500 Western Australian
horses was administered in two sections. The first section was completed by the
owner and referred to the horse's signalment, diet and husbandry conditions. The
second section was completed by veterinarians and focused on the horse's oral
health. A multivariable logistic regression model was used to assess risk factors
associated with peripheral caries. RESULTS: Peripheral caries was present in
58.8% (95% confidence interval [CI] 54.5-63.1%) of surveyed horses. Breed was
significantly associated with peripheral caries, with Warmbloods (odds ratio [OR]
0.44, 95% CI 0.24-0.82; P = 0.009) and Western breeds (OR 0.38, 95% CI 0.19-0.78;
P = 0.008) being less likely to have peripheral caries than Thoroughbreds.
Dietary risk factors included oaten hay (OR 2.90, 95% CI 1.87-4.53; P<0.001). A
meadow hay-based diet was protective (OR 0.47, 95% CI 0.27-0.80; P = 0.005).
Horses with access to quality pasture all year were less likely to have
peripheral caries than horses without access to grazing (OR 0.31, 95% CI 0.15
0.66; P = 0.002), as were horses on groundwater compared with horses on rainwater
(OR 3.35, 95% CI 1.65-6.78; P = 0.001), drinking water (OR 2.03, 95% CI 1.14
3.62; P = 0.016) or dam water (OR 3.53, 95% CI 1.08-11.53; P = 0.037). Peripheral
caries was positively correlated with periodontal disease (OR 4.53, 95% CI 2.91
7.06; P<0.001) and feed packing (feed present between the teeth without
significant periodontal pocketing) (OR 1.94, 95% CI 1.32-2.85; P = 0.001). MAIN
LIMITATIONS: Not every owner of eligible horses seen during the study period
agreed to participate. An epidemiological study is unable to show causality.
CONCLUSIONS: Western Australian horses have a high prevalence of peripheral
caries. Management factors that may help to prevent or reduce peripheral caries
include more access to quality pasture, use of groundwater, feeding on meadow hay
and avoidance of oaten hay.
PMID- 28707364
TI - Furosemide use and acute risk of hip fracture in older people: A nationwide case
control study in Taiwan.
AB - AIM: Little is known about the acute effects of furosemide use on the risk of hip
fracture. The aim of the present study was to evaluate the association between
furosemide use and acute risk of hip fracture in older people in Taiwan. METHODS:
We carried out a retrospective nationwide case-control study using the database
of the Taiwan National Health Insurance Program. A total of 4523 older adults
aged >=65 years with newly diagnosed hip fracture from 2000 to 2013 were
identified as the cases. Additionally, 4523 older adults aged >=65 years without
hip fracture were randomly selected as the controls. The cases and the controls
were matched by sex, age, comorbidities, and index year and month of hip fracture
diagnosis. Furosemide use was defined as "current," "recent" or "past" if the
furosemide prescription was filled <3 months, 3-6 months or >=6 months before the
date of hip fracture diagnosis, respectively. The unconditional logistic
regression model was used to calculate the odds ratio and 95% confidence interval
(CI) for the relative risk of hip fracture associated with furosemide use.
RESULTS: After adjustment for potential covariables, the adjusted odds ratios of
hip fracture were 1.30 for participants with current use of furosemide (95% CI
1.14-1.48), 1.23 for participants with recent use of furosemide (95% CI 0.98
1.53) and 1.08 for participants with past use of furosemide (95% CI 0.90-1.30),
compared with non-users. CONCLUSIONS: Current use of furosemide is associated
with a 30% increased odds of hip fracture in older people in Taiwan. Geriatr
Gerontol Int 2017; 17: 2552-2558.
PMID- 28707366
TI - Abstracts of the 3rd Congress of the European Academy of Neurology, Amsterdam,
The Netherlands, June 2017.
PMID- 28707365
TI - Use of 3-D digital subtraction rotational angiography during cardiac
catheterization of infants and adults with congenital heart diseases.
AB - OBJECTIVE: To compare image quality, radiation and contrast doses required to
obtain 3D-Digital subtraction rotational angiography (3D-DSRA) with 3D-Digital
rotational angiography (3D-DRA) in infants (children <= 2 years of age) and
adults with congenital heart diseases (ACHD). BACKGROUND: 3D-DRA can be performed
with radiation doses comparable to bi-plane cine-angiography. However, 3D-DRA in
infants requires a large contrast volume. The resolution of 3D-DRA performed in
ACHD patients is limited by their soft tissue density. We hypothesized that the
use of 3D-DSRA could help alleviate these concerns. METHODS: Radiation (DAP) and
contrast doses required to obtain 3D-DSRA was compared with 3D-DRA in 15 age-,
size-, and intervention-matched infants and 15 ACHD patients. The diagnostic
quality and utility of these two modalities were scored by 4 qualified
independent observers. RESULTS: Both in infants and adults, the median contrast
volume for 3D-DSRA was lower than 3D-DRA (0.98 vs. 1.81 mL/kg; P < 0.001 and 0.92
vs. 1.4 mL/kg; P < 0.001, respectively) with an increased DAP (median: 188 vs.
128 cGy cm2 ; P = 0.068 and 659 vs. 427 cGy cm2 ; P = 0.045, respectively). The
diagnostic quality and utility scores for rotational-angiography, and 3D
reconstruction were superior for 3D-DSRA (score = 94 vs. 80%, P = 0.03 and 90
vs.79%, P = 0.01, respectively) and equivalent for multi-planar-reformation and
3D-roadmapping in ACHD patients compared with 3D-DRA. All scores for both
modalities were equivalent for infants. CONCLUSIONS: 3D-DSRA can be acquired
using lower contrast volume with a mildly higher radiation dose than 3D-DRA in
infants and ACHD patients. The diagnostic quality and utility scores for 3D-DSRA
were higher in ACHD patients and equivalent for infants compared with 3D-DRA.
PMID- 28707367
TI - Colloidal Synthesis of Silicon-Carbon Composite Material for Lithium-Ion
Batteries.
AB - We report colloidal routes to synthesize silicon@carbon composites for the first
time. Surface-functionalized Si nanoparticles (SiNPs) dissolved in styrene and
hexadecane are used as the dispersed phase in oil-in-water emulsions, from which
yolk-shell and dual-shell hollow SiNPs@C composites are produced via
polymerization and subsequent carbonization. As anode materials for Li-ion
batteries, the SiNPs@C composites demonstrate excellent cycling stability and
rate performance, which is ascribed to the uniform distribution of SiNPs within
the carbon hosts. The Li-ion anodes composed of 46 wt % of dual-shell SiNPs@C, 46
wt % of graphite, 5 wt % of acetylene black, and 3 wt % of carboxymethyl
cellulose with an areal loading higher than 3 mg cm-2 achieve an overall specific
capacity higher than 600 mAh g-1 , which is an improvement of more than 100 %
compared to the pure graphite anode. These new colloidal routes present a
promising general method to produce viable Si-C composites for Li-ion batteries.
PMID- 28707368
TI - Isolation and characterization of metaldehyde-degrading bacteria from domestic
soils.
AB - Metaldehyde is a common molluscicide, used to control slugs in agriculture and
horticulture. It is resistant to breakdown by current water treatment processes,
and its accumulation in drinking water sources leads to regular regulatory
failures in drinking water quality. To address this problem, we isolated
metaldehyde-degrading microbes from domestic soils. Two distinct bacterial
isolates were cultured, that were able to grow prototrophically using metaldehyde
as sole carbon and energy source. One isolate belonged to the genus Acinetobacter
(strain designation E1) and the other isolate belonged to the genus Variovorax
(strain designation E3). Acinetobacter E1 was able to degrade metaldehyde to a
residual concentration < 1 nM, whereas closely related Acinetobacter strains were
completely unable to degrade metaldehyde. Variovorax E3 grew and degraded
metaldehyde more slowly than Acinetobacter E1, and residual metaldehyde remained
at the end of growth of the Variovorax E3 strain. Biological degradation of
metaldehyde using these bacterial strains or approaches that allow in situ
amplification of metaldehyde-degrading bacteria may represent a way forward for
dealing with metaldehyde contamination in soils and water.
PMID- 28707369
TI - Psychological stress affects the severity of radiation-induced acute skin
reactions in breast cancer patients.
AB - Psychological stress exacerbates many pathological conditions including
inflammatory skin conditions. The effect of psychological stress on acute
radiation-induced skin reactions has not been documented before. Here, we aimed
to explore if psychological stress could aggravate skin reaction severity in
breast cancer patients. We conducted a secondary analysis of patient data
obtained during a randomised, controlled clinical trial for acute radiation
induced skin reaction severity in 78 breast cancer patients. Patients were
assessed three times a week during treatment. Skin reaction severity was measured
using the modified Radiation-Induced Skin Reaction Assessment Scale (RISRAS) and
Radiation Therapy Oncology Group grades. Stress levels were determined using a 5
point LIKERT scale to rate physical well-being, managing stress levels, house,
family, work and other commitments. A total of 20 patients (26%) of the 78
patient cohort were considered stressed. Skin reaction severity in stressed
patients was twice that of non-stressed patients (p < 0.001) and stressed
patients were five times more likely to develop moist desquamation. Our results
show that psychological stress aggravates skin reaction severity during radiation
therapy. This research needs to be validated in a more rigorous manner by
incorporating a validated scale such as the Distress Thermometer and Impact
Thermometer in future skin trials.
PMID- 28707370
TI - Chiral Manganese Aminopyridine Complexes: the Versatile Catalysts of Chemo- and
Stereoselective Oxidations with H2 O2.
AB - In the last decade, manganese(II) complexes with N-donor tetradentate
aminopyridine ligands emerged as efficient catalysts of enantioselective
epoxidation of olefins and direct selective oxidation of C-H groups in complex
organic molecules, with environmentally benign oxidant hydrogen peroxide. In this
personal account, we summarize the progress of these catalysts with regard to
ligands design, structure-reactivity correlations, evaluation of the substrate
scope, as well as mechanistic studies, shedding light on the nature of active
sites and the mechanisms of selective oxygenations. Several practically promising
catalytic syntheses with the aid of Mn aminopyridine catalysts are exemplified.
PMID- 28707372
TI - Facile Synthesis of Azetidine Nitrones and Diastereoselective Conversion into
Densely Substituted Azetidines.
AB - An electrocyclization route to azetidine nitrones from N-alkenylnitrones was
discovered that provides facile access to these unsaturated strained
heterocycles. Reactivity studies showed that these compounds undergo a variety of
reduction, cycloaddition, and nucleophilic addition reactions to form highly
substituted azetidines with excellent diastereoselectivity. Taken together, these
transformations provide a fundamentally different approach to azetidine synthesis
than traditional cyclization by nucleophilic displacement and provide novel
access to a variety of underexplored strained heterocyclic compounds.
PMID- 28707371
TI - Individuals with sickle cell disease have a significantly greater
vasoconstriction response to thermal pain than controls and have significant
vasoconstriction in response to anticipation of pain.
AB - The painful vaso-occlusive crises (VOC) that characterize sickle cell disease
(SCD) progress over hours from the asymptomatic steady-state. SCD patients report
that VOC can be triggered by stress, cold exposure, and, pain itself. We
anticipated that pain could cause neural-mediated vasoconstriction, decreasing
regional blood flow and promoting entrapment of sickle cells in the
microvasculature. Therefore, we measured microvascular blood flow in the fingers
of both hands using plethysmography and laser-Doppler flowmetry while applying a
series of painful thermal stimuli on the right forearm in 23 SCD patients and 25
controls. Heat pain applied to one arm caused bilateral decrease in microvascular
perfusion. The vasoconstriction response started before administration of the
thermal pain stimulus in all subjects, suggesting that pain anticipation also
causes significant vasoconstriction. The time delay between thermal pain
application and global vasoconstriction ranged from 5 to 15.5 seconds and
increased with age (P < .01). Although subjective measures, pain threshold and
pain tolerance were not different between SCD subjects and controls, but the vaso
reactivity index characterizing the microvascular blood flow response to painful
stimuli was significantly higher in SCD patients (P = .0028). This global
vasoconstriction increases microvascular transit time, and may promote entrapment
of sickle cells in the microvasculature, making vaso-occlusion more likely. The
rapidity of the global vasoconstriction response indicates a neural origin that
may play a part in the transition from steady-state to VOC, and may also
contribute to the variability in VOC frequency observed in SCD patients.
PMID- 28707373
TI - Biomarker responses and PAH ratios in fish inhabiting an estuarine urban
waterway.
AB - Many cities worldwide are established adjacent to estuaries and their catchments
resulting in estuarine contamination due to intense anthropogenic activities. The
aim of this study was to evaluate if fish living in an estuarine urban waterway
were affected by contamination, via the measurement of a suite of biomarkers of
fish health. Black bream (Acanthopagrus butcheri) were sampled in a small urban
embayment and a suite of biomarkers of fish health measured. These were condition
factor (CF), liver somatic index (LSI), gonadosomatic index (GSI), hepatic EROD
activity, polycyclic aromatic hydrocarbon (PAH) biliary metabolites, serum
sorbitol dehydrogenase (s-SDH) and branchial enzymes cytochrome C oxidase (CCO),
and lactate dehydrogenase (LDH) activities. The biomarkers of exposure EROD
activity, and pyrene- and B(a)P-type biliary metabolites confirmed current or
recent exposure of the fish and that fish were metabolizing contaminants.
Relative to a reference site, LSI was higher in fish collected in the urban inlet
as was the metabolic enzyme LDH activity. CF, GSI, s-SDH, CCO, and naphthalene
type metabolites were at similar levels in the urban inlet relative to the
reference site. PAH biliary metabolite ratios of high-molecular-weight to low
molecular-weight suggest that fish from the urban inlet were exposed to pyrogenic
PAHs, likely from legacy contamination and road runoff entering the embayment.
Similarly, the sediment PAH ratios and the freshness indices suggested legacy
contamination of a pyrogenic source, likely originating from the adjacent
historic gasworks site and a degree of contamination of petrogenic nature
entering the inlet via storm water discharge. Biomarkers of exposure and effect
confirmed that black bream collected in the Claisebrook Cove inlet, Western
Australia, are currently exposed to contamination and are experiencing metabolic
perturbations not observed in fish collected at a nearby reference site.
PMID- 28707374
TI - Localization and functional analysis of the insect-specific RabX4 in the brain of
Bombyx mori.
AB - Rab proteins are small monomeric GTPases/GTP-binding proteins, which form the
largest branch of the Ras superfamily. The different Rab GTPases are localized to
the cytosolic face of specific intracellular membranes, where they function as
regulators of distinct steps in membrane trafficking. RabX4 is an insect-specific
Rab protein that has no close homolog in vertebrates. There is little information
about insect-specific Rab proteins. RabX4 was expressed in Escherichia coli and
subsequently purified. Antibodies against Bombyx mori RabX4 were produced in
rabbits for western immunoblotting and immunohistochemistry. Western blotting of
neural tissues revealed a single band, at approximately 26 kD. RabX4-like
immunohistochemical reactivity was restricted to neurons of the pars
intercerebralis and dorsolateral protocerebrum in the brain. Further
immunohistochemical analysis revealed that RabX4 colocalized with Rab6 and
bombyxin in the corpus allatum, a neuronal organ that secretes neuropeptides
synthesized in the brain into the hemolymph. RabX4 expression in the frontal
ganglion, part of the insect stomatogastric nervous system that is found in most
insect orders, was restricted to two neurons on the outer region and did not
colocalize with allatotropin or Rab6. Furthermore, RNA interference of RabX4
decreased bombyxin expression levels in the brain. These findings suggest that
RabX4 is involved in the neurosecretion of a secretory organ in Bombyx mori.
PMID- 28707375
TI - Clinical outcomes with reservoir-based polymer-free amphilimus-eluting stents in
real-world patients according to diabetes mellitus and complexity: The INVESTIG8
registry.
AB - BACKGROUND: Patients with diabetes mellitus (DM) remain at higher risk of
restenosis after percutaneous coronary intervention despite the use of
contemporary drug-eluting stents. The Cre8 amphilimus-eluting stent (AES) has
shown promising results in DM patients. Whether this holds true irrespective of
patient's clinical and angiographic complexity is unknown. METHODS: Five hundred
and ninety five consecutive patients (738 lesions) undergoing AES implantation
were included in the INVESTIG8 multicenter registry. Patients were stratified
according to DM status and further stratified according to patients' complexity.
The prespecified primary endpoint was target lesion failure (TLF)-defined as the
composite of cardiac death, target-vessel myocardial infarction, and target
lesion revascularization (TLR). RESULTS: DM patients were more often complex as
compared to non-DM patients (70% vs. 61%, P = 0.015). At 18-month follow-up,
there was a trend to a higher TLF rate in DM than in non-DM patients (6.9% vs.
3.5%, P = 0.063). This was largely driven by a markedly higher risk of TLF among
complex DM patients as compared to simple DM patients (8.9% vs. 2.4%, P = 0.053).
A multivariate analysis identified complexity (HR 6.11, 95% CI: 1.42-26.2) but
not DM (HR 1.59; 95% CI 0.71-3.56) as an independent predictor of TLF. Of note,
TLR rates were similar between DM and non-DM patients (3.3% vs. 1.9%, P = 0.228).
CONCLUSIONS: In this real-world, multicenter registry the Cre8 AES showed
favorable clinical outcomes in DM patients. Increased risk of TLF appears to be
driven by patients' complexity rather than DM status. These findings will need to
be confirmed in a large-scale randomized trial.
PMID- 28707376
TI - Immunosenescence Induced by Plasma from Individuals with Obesity Caused Cell
Signaling Dysfunction and Inflammation.
AB - OBJECTIVE: To evaluate the consequences of plasma from individuals with obesity
on parameters associated with immunosenescence in unrelated healthy peripheral
blood mononuclear cells (PBMC). METHODS: Freshly isolated PBMC were incubated in
media supplemented with 10% of plasma from individuals with obesity or control
subjects for the first 4 hours of 24 to 120 hours of culture. RESULTS: Plasma
from individuals with obesity modulated the phenotype of healthy PBMC, leading to
a higher rate of apoptosis, lower amounts of phospho-gammaH2AX and -p53, and
mitochondrial dysfunction. After 120 hours, there was a higher secretion of
inflammatory cytokines IL-1beta and IL-8. CD8+ T lymphocytes presented decreased
expression of CD28, which is associated with the immunosenescent phenotype. CD14+
macrophages showed increased expression of CD80 and CD206, suggesting a
modulation in the activation of macrophages. CONCLUSIONS: These results
demonstrate that chronic systemic inflammation observed in obesity induces
dysfunctional features in PBMC that are consistent with premature
immunosenescence.
PMID- 28707377
TI - Glycemia in Acute Stroke II study: a call to improve post-stroke hyperglycemia
management in clinical practice.
AB - BACKGROUND AND PURPOSE: The aim of the study was to analyze the effect of
conventional glucose management, which aimed to maintain glucose levels <155
mg/dL (8.5 mmol/L), on glucose control and the outcomes of patients with acute
ischaemic stroke (IS) in a clinical practice setting. METHODS: This was a
multicenter, prospective cohort study of patients with acute IS. Patients were
classified into four groups based on their initial 48-h capillary glucose levels
and the administration of and response to corrective treatment: (i) untreated and
maximum glucose levels <155 mg/dL (8.5 mmol/L) within the first 48 h; (ii)
treated and good responders [glucose levels persistently <155 mg/dL (8.5
mmol/L)]; (iii) treated and non-responders [any glucose values >=155 mg/dL (8.5
mmol/L) during the 24 h after the start of corrective treatment]; and (iv)
untreated with any glucose value >=155 mg/dL (8.5 mmol/L). The primary outcome
was death or dependence at 3 months (blinded rater). RESULTS: A total of 213
patients were included. Ninety-seven (45.5%) patients developed glucose levels
>=155 mg/dL (8.5 mmol/L), 69 (71.1%) underwent corrective treatment and 31
patients underwent no corrective treatment at the physician's discretion [28 of
whom had isolated values >=155 mg/dL (8.5 mmol/L)]. Only 11 (16%) patients
responded to conventional treatment, whereas 58 (84%) patients were non
responsive. Non-responders showed a twofold higher risk of death or dependence at
3 months (odds ratio, 2.472; 95% confidence interval, 1.096-5.576; P = 0.029).
CONCLUSIONS: Lack of response to conventional treatment for glucose management in
acute IS is frequent and associated with poor outcomes.
PMID- 28707378
TI - A Lithium Ion Highway by Surface Coordination Polymerization: In Situ Growth of
Metal-Organic Framework Thin Layers on Metal Oxides for Exceptional Rate and
Cycling Performance.
AB - A thin layer of a highly porous metal-organic framework material, ZIF-8, is
fabricated uniformly on the surface of nanostructured transition metal oxides
(ZnO nanoflakes and MnO2 nanorods) to boost the transfer of lithium ions. The
novel design and uniform microstructure of the MOF-coated TMOs (ZIF-8@TMOs)
exhibit dramatically enhanced rate and cycling performance comparing to their
pristine counterparts. The capacities of ZIF-8@ZnO (nanoflakes) and ZIF-8@MnO2
(nanorods) are 28 % and 31 % higher that of the pristine ones at the same current
density. The nanorods of ZIF-8@MnO2 show a capacity of 1067 mAh g-1 after 500
cycles at 1 Ag-1 and without any fading. To further improve the conductivity and
capacity, the ZIF-8-coated materials are pyrolyzed at 700 degrees C in an N2
atmosphere (ZIF-8@TMO-700 N). After pyrolysis, a much higher capacity improvement
is achieved: ZIF-8@ZnO-700 N and ZIF-8@MnO2 -700 N have 54 % and 69 % capacity
increases compared with the pristine TMOs, and at 1 Ag-1 , the capacity of ZIF
8@MnO2 -700 N is 1060 mAh g-1 after cycling for 300 cycles.
PMID- 28707379
TI - Three- and 6-month optical coherence tomographic surveillance following
percutaneous coronary intervention with the Angiolite(r) drug-eluting stent: The
ANCHOR study.
AB - BACKGROUND: Pre-clinical results of a novel open-cell, thin strut, durable
polymer, laser cut cobalt chromium sirolimus-eluting stent (Angiolite) were
promising. Using quantitative optical coherence tomographic (OCT) analyses, we
explored the healing characteristics of the Angiolite DES system at 3- and 6
months post implantation. METHODS: A total of 103 patients with de novo coronary
lesions underwent percutaneous coronary intervention with the Angiolite DES and
were randomized 1:3 into two cohorts for angiographic and OCT follow-up, with 28
and 70 patients returning for 3- or 6-month post-PCI surveillance, respectively.
The primary endpoints were the 6-month rates of OCT-derived neointimal
proliferation, strut coverage and incomplete strut apposition (ISA), whilst the
secondary endpoints were 3-month OCT-derived measures of strut coverage and ISA,
as well as 6-month quantitative coronary angiographic-derived measures [late
lumen loss (LLL), binary restenosis]. RESULTS: The Angiolite stent was
successfully implanted in all patients, without periprocedural complications. At
3- and 6-months follow-up, OCT strut coverage was evident in 86.3% and 83.3% of
struts, mean neointimal thickness was 73.7 +/- 46.5 MUm and 73.9 +/- 54.3 MUm,
mean neo-intimal area obstruction of 5.8% +/-10.3% and 4.4% +/- 11.3%, and ISA
rates were 1.3% +/- 7.3% and 1.1% +/- 6.2%, respectively. In-stent LLL at 6
months was 0.07 +/- 0.37 mm, with a binary in-stent angiographic restenosis rate
of 0% without any stent thrombosis, myocardial infarction or cardiovascular
death, with 1 patient undergoing ischemia-driven target-lesion revascularization.
CONCLUSIONS: At 6 months, the Angiolite DES was safe with high rates of strut
coverage, modest degrees of neointimal hyperplasia and very low rates of strut
malapposition. These data coupled with the absence of in-stent binary restenosis
and a very low 6-month in-stent LLL point towards an efficacious DES. Future
studies are required to evaluate its efficacy in broader lesion subsets with
longer follow-up.
PMID- 28707380
TI - Pre-hospital and retrieval medicine clinical governance in Sydney and the
inconvenient truth.
PMID- 28707381
TI - Radiation-associated lens changes in the cardiac catheterization laboratory:
Results from the IC-CATARACT (CATaracts Attributed to RAdiation in the CaTh lab)
study.
AB - OBJECTIVE: To examine the relationship between occupational exposure to ionizing
radiation and the prevalence of lens changes in interventional cardiologists
(ICs) and catheterization laboratory ("cath-lab") staff. BACKGROUND: Exposure to
ionizing radiation is associated with the development of lens opacities. ICs and
cath-lab staff can receive high doses of ionizing radiation without protection,
and may thus be at risk for lens opacity formation. METHODS: We conducted a cross
sectional study at an interventional cardiology conference. Study participants
completed a questionnaire pertaining to occupational exposure to radiation and
potential confounders for the development of cataracts, followed by slit-lamp
examination and grading of lens findings. RESULTS: A total of 117 attendees
participated in the study, including 99 (85%; 49 +/- 11 years-old; 82% male) with
occupational exposure to ionizing radiation and 18 (15%; 39 +/- 12 years-old; 61%
male) unexposed controls. The prevalence of overall cortical and posterior
subcapsular lens changes (including subclinical findings) was higher in exposed
participants compared with controls (47 vs. 17%, P = 0.015). Occupational
exposure and age over 60 were independent predictors of lens changes (odds ratio
[95% CI]: 6.07 [1.38-43.45] and 7.72 [1.60-43.34], respectively). The prevalence
of frank opacities was low and similar between the two groups (14 vs. 6%, P =
0.461). Most lens findings consisted of subclinical changes in the periphery of
the lens without impact on visual acuity. CONCLUSIONS: Compared with unexposed
controls, ICs and cath-lab staff had a higher prevalence of lens changes that may
be attributable to ionizing radiation exposure. While most of these changes were
subclinical, they are important due to the potential to progress to clinical
symptoms, highlighting the importance of minimizing staff radiation exposure.
PMID- 28707382
TI - Neutron crystallographic studies of T4 lysozyme at cryogenic temperature.
AB - Bacteriophage T4 lysozyme (T4L) has been used as a paradigm for seminal
biophysical studies on protein structure, dynamics, and stability. Approximately
700 mutants of this protein and their respective complexes have been
characterized by X-ray crystallography; however, despite the high resolution
diffraction limits attained in several studies, no hydrogen atoms were reported
being visualized in the electron density maps. To address this, a 2.2 A
resolution neutron data set was collected at 80 K from a crystal of perdeuterated
T4L pseudo-wild type. We describe a near complete atomic structure of T4L, which
includes the positions of 1737 hydrogen atoms determined by neutron
crystallography. The cryogenic neutron model reveals explicit detail of the
hydrogen bonding interactions in the protein, in addition to the protonation
states of several important residues.
PMID- 28707383
TI - Two cases of early recurrence after transabdominal preperitoneal inguinal hernia
repair.
AB - We performed transabdominal preperitoneal inguinal hernia repair in 46 patients
(58 diseases), two of whom experienced early recurrence after mesh repair. Case 1
was a 76-year-old man with a bilateral inguinal hernia (recurrence site, left
indirect hernia) after appendectomy. The recurrence occurred 1 month after
transabdominal preperitoneal inguinal hernia repair. The mesh was dislocated to
the lateral side, and we repaired it using the direct Kugel(r) patch with an
anterior technique. Case 2 was a 79-year-old man with a bilateral inguinal hernia
(recurrence site, right direct hernia with an orifice >3 cm) after appendectomy.
The recurrence occurred 3 months after transabdominal preperitoneal inguinal
hernia repair. The mesh was dislocated to the lateral side, and we repaired it
using an ULTRAPRO(r) Plug with an anterior technique under laparoscopic
observation. We believe the recurrences resulted from insufficient internal
exfoliation and fixation affected by complicated exfoliation of the preperitoneal
space with omental adhesion after intraperitoneal surgery.
PMID- 28707384
TI - A Visual Analog Scale to assess anxiety in children during anesthesia induction
(VAS-I): Results supporting its validity in a sample of day care surgery
patients.
AB - BACKGROUND: The modified Yale Preoperative Anxiety Scale is widely used to assess
children's anxiety during induction of anesthesia, but requires training and its
administration is time-consuming. A Visual Analog Scale, in contrast, requires no
training, is easy-to-use and quickly completed. AIM: The aim of this study was to
evaluate a Visual Analog Scale as a tool to assess anxiety during induction of
anesthesia and to determine cut-offs to distinguish between anxious and
nonanxious children. METHODS: Four hundred and one children (1.5-16 years)
scheduled for daytime surgery were included. Children's anxiety during induction
was rated by parents and anesthesiologists on a Visual Analog Scale and by a
trained observer on the modified Yale Preoperative Anxiety Scale. Psychometric
properties assessed were: (i) concurrent validity (correlations between parents'
and anesthesiologists' Visual Analog Scale and modified Yale Preoperative Anxiety
Scale scores); (ii) construct validity (differences between subgroups according
to the children's age and the parents' anxiety as assessed by the State-Trait
Anxiety Inventory); (iii) cross-informant agreement using Bland-Altman analysis;
(iv) cut-offs to distinguish between anxious and nonanxious children (reference:
modified Yale Preoperative Anxiety Scale >=30). RESULTS: Correlations between
parents' and anesthesiologists' Visual Analog Scale and modified Yale
Preoperative Anxiety Scale scores were strong (0.68 and 0.73, respectively).
Visual Analog Scale scores were higher for children <=5 years compared to
children aged >=6. Visual Analog Scale scores of children of high-anxious parents
were higher than those of low-anxious parents. The mean difference between
parents' and anesthesiologists' Visual Analog Scale scores was 3.6, with 95%
limits of agreement (-56.1 to 63.3). To classify anxious children, cut-offs for
parents (>=37 mm) and anesthesiologists (>=30 mm) were established. CONCLUSIONS:
The present data provide preliminary data for the validity of a Visual Analog
Scale to assess children's anxiety during induction.
PMID- 28707385
TI - Risk Factors of Lower Urinary Tract Syndrome among Ketamine Users.
AB - OBJECTIVE: This study investigated the risk factors of ketamine associated-lower
urinary tract symptoms (LUTS), such as duration of use, dosage of ketamine, co
occurring substance use of other psychoactive drugs, comorbidities, and
depression. METHODS: This study was a cross-sectional survey. LUTS was assessed
with the O'Leary symptom and problem index (OSPI) scores. We included the
comorbidities of interstitial cystitis/painful bladder syndrome (IC/PBS) as
comorbid factors. Depression was evaluated based on the Diagnostic and
Statistical Manual of Mental Disorders, Fifth Edition (DSM 5). Duration of use,
dosage of ketamine and the OSPI scores were subjected to log transformation
because of the skewed distribution. RESULT: Among 143 participating ketamine
users, 25 (17.5%) had LUTS. Duration of ketamine use was significantly positively
correlated with OSPI scores (adjusted beta [95% CI], 0.21 [0.06-0.35] in log-log
model), which equaled a 10% increase in months of ketamine-use increased OSPI
scores by 2.02 %. Female and depression were significantly associated OSPI scores
(adjusted beta [95% CI], 0.20 [0.03-0.37], 0.49 [0.29-0.70], respectively in the
log-linear model), with OSPI scores being 1.22 times higher in female, and 1.63
times higher in ketamine users with depression. Dosage of use was not
significantly associated with OSPI scores (adjusted beta [95% CI], 0.04 [-0.12 to
0.20], P = 0.64 in log-log model), likewise with comorbid diseases (adjusted beta
[95% CI], 0.07 [-0.08 to 0.21], P = 0.36 in log-linear model). CONCLUSION:
Depression and longer duration of exposure to ketamine are significantly
associated with the development of LUTS among ketamine users. Early evaluation
and intervention of depression should be considered in patients of ketamine
associated LUTS.
PMID- 28707386
TI - Efficacy and safety of a coagulated thrombus injection for peripheral artery
perforation: The coagulated thrombus hemostasis method.
AB - BACKGROUND: This retrospective study assesses the safety and efficacy of using a
thrombus injection for treatment a peripheral artery perforation. METHODS AND
RESULTS: From March 2013 to April 2016, we performed 1,152 endovascular treatment
(EVT) at our hospital. Of these, 28 peripheral artery perforations occurred
during the EVT procedure and 20 were treated with a thrombus, which we
artificially created. The thrombus comprised the patient's blood and thrombin. It
was injected into the perforation site from the tip of an over-the-wire balloon
using ballooning method. The perforated arteries occurred in below-the-knee
artery (45%), superficial femoral artery (35%), deep femoral artery (10%),
popliteal artery (5%), and external iliac artery (5%). Thrombus injection was
successful in 19 of the 20 perforations (95%). One patient required coil
embolization. There were no complications during or after admission. CONCLUSIONS:
Thrombus injection is a safety method and might be considered as one of the
approaches for stopping peripheral artery perforation.
PMID- 28707387
TI - Effects of nurses' personality traits and their environmental characteristics on
their workplace learning and nursing competence.
AB - AIM: A good fit between an individual's personality traits and job
characteristics motivates employees, and thus enhances their work behavior.
However, how nurses' personality traits and their environmental characteristics
relate to nurses' engagement in workplace learning, which improves their
competence, has not been investigated. The aim of this study was to investigate
how nurses' personality traits, environmental characteristics, and workplace
learning were related to nursing competence. METHODS: A cross-sectional survey
design was used. Questionnaires were distributed to 1167 Japanese registered
nurses. Multiple regression analysis was used to examine the relationships
between nurses' personality traits, the environmental characteristics, the
nurses' engagement in workplace learning, and their competence. RESULTS: A total
of 315 nurses returned questionnaires (i.e., a return rate of 27.0%). The results
showed that both the personality traits (extraversion, conscientiousness,
openness to experience) and environmental characteristics (autonomy at work and
feedback given) were related to workplace learning and self-rated nursing
competence. The results also showed that the relationship between extraversion
(active, adventurous and ambitious dispositions of an individual) and self-rated
nursing competence was moderated by environmental characteristics, and partially
mediated by workplace learning. CONCLUSION: Positive personality traits, such as
extraversion, conscientiousness, and openness to experience could enhance
workplace learning and nursing competence. Moreover, environmental
characteristics that allow nurses to express their personality traits have the
potential to improve their learning and competence further.
PMID- 28707388
TI - The associations of large-for-gestational-age and infant feeding practices with
children's body mass index z-score trajectories: the Early Childhood Longitudinal
Study, Birth Cohort.
AB - Very few studies have examined if high birth weight and infant feeding practices
have implications for the trajectory of body mass index (BMI) growth across the
early childhood period. The goal of this study was to assess if large-for
gestational-age (LGA) and infant feeding practices (exclusive breastfeeding for 6
months, and early introduction of complementary food prior to 4 months) are
associated with BMI z-score trajectories over the early childhood period. Group
based trajectory modelling (GBTM) methods were employed to describe and classify
developmental BMI z-score trajectories (the outcome of interest) in children from
9 months to 4 years of age (n = 4497) born to prenatal non-smoking mothers in the
Early Childhood Longitudinal Study, Birth Cohort (2001-2005). Further analyses
examined if the identified BMI z-score trajectories varied systematically with
the exposures, LGA and specific infant feeding practices, after accounting for
sociodemographic and other early-life factors. Two BMI z-score trajectory groups
were identified: normal BMI z-score (56.2%) and high BMI z-score (43.8%).
Children who were LGA infants had 2.3 times (risk ratio 95% confidence interval:
1.2, 4.5) greater risk of being in high BMI z-score group relative to normal BMI
z-score group. BMI z-score trajectory groups did not differ by infant feeding
practices, after controlling for LGA at birth. Membership in the high BMI z-score
group was associated with LGA, but not with infant feeding practices. Healthcare
professionals should provide early obesity counselling to parents of LGA infants
so that parents can take appropriate obesity prevention measures for their
children.
PMID- 28707389
TI - Methamphetamine promotes habitual action and alters the density of striatal
glutamate receptor and vesicular proteins in dorsal striatum.
AB - Goal-directed actions are controlled by the value of the consequences they
produce and so increase when what they produce is valuable and decrease when it
is not. With continued invariant practice, however, goal-directed actions can
become habits, controlled not by their consequences but by antecedent, reward
related states and stimuli. Here, we show that pre-exposure to methamphetamine
(METH) caused abnormally rapid development of habitual control. Furthermore,
these drug-induced habits differed strikingly from conventional habits; we found
that they were insensitive both to changes in reward value and to the effects of
negative feedback. In addition to these behavioral changes, METH exposure
produced bidirectional changes to synaptic proteins in the dorsal striatum. In
the dorsomedial striatum, a structure critical for goal-directed action, METH
exposure was associated with a reduction in glutamate receptor and glutamate
vesicular proteins, whereas in the dorsolateral striatum, a region that has
previously been implicated in habit learning, there was an increase in these
proteins. Together, these results indicate that METH exposure promotes habitual
control of action that appears to be the result of bidirectional changes in
glutamatergic transmission in the circuits underlying goal-directed and habit
based learning.
PMID- 28707390
TI - Social capital in Japan: What characteristics do public health nurses see in
their communities?
AB - AIM: A concept of social capital that accounts for a community's cultural
background and incorporates social capital into public health nursing practice
are needed. This study aimed to describe the characteristics of social capital in
the context of public health nursing in Japan. METHODS: The study interviewed 11
veteran public health nurses from five municipalities across Japan and undertook
a qualitative research analysis. A digital voice recorder was used to collect
qualitative data by using a background data sheet and semistructured interviews.
Trustworthiness in interpreting the data was ensured by conducting 13 additional
interviews with residents and collating the two sets of results. RESULTS: All the
participants were female: 10 were veterans with >=15 years' experience. Nine
worked in management. The methods yielded six categories: (i) the richness of the
interactions among the residents; (ii) the community residents who showed concern
for those in need; (iii) community civic activities; (iv) the residents'
willingness to contribute to the community; (v) the health promotion volunteers
who work alongside the public health nurses; and (vi) an enriched community
environment. CONCLUSION: The results contribute to an understanding of social
capital in the context of public health nursing activities and further research
on social capital. It also is discussed how social capital can be incorporated
into public health nursing activities in the future.
PMID- 28707391
TI - Role of sentinel lymph node biopsy as a staging procedure in patients with
melanoma: A critical appraisal.
AB - Worldwide, sentinel node (SN) biopsy for accurate staging is now part of the
standard work-up of patients with melanomas >=1.0 mm Breslow thickness, as it is
for staging patients with breast cancer. Nuclear medicine imaging and surgical
techniques have evolved to such a degree that a SN can be identified and removed
in virtually every patient. Nevertheless, some opposition to a routine SN biopsy
remains, perhaps due to a failure to appreciate the serious implications of
incomplete or inaccurate staging. Guided by a critical appraisal of the available
evidence, this review elucidates the definition of an SN, discusses the
sensitivity and specificity of the information it provides, emphasises that it is
a minor staging procedure that can lead to improved survival when followed by
appropriate therapy, and explains the necessarily unconventional and complex
design of the only randomised trial that addresses this subject. It also
describes other benefits and risks of an SN biopsy and outlines its role in
current melanoma management.
PMID- 28707392
TI - Stable coronary artery disease and left ventricular dysfunction: The role of
revascularization.
AB - The aim of this review is to present existing evidence of revascularization in
patients with stable coronary artery disease (CAD) and left ventricular (LV)
dysfunction. A literature review was performed for trials studying
revascularization, via CABG or PCI, in patients with CAD and LV dysfunction.
Pivotal, high-quality trials have investigated revascularization with CABG in
stable CAD and LV dysfunction. CASS demonstrated improved 10-year survival in the
surgical group compared to medically treated patients. While 56-month follow-up
of the STICH trial found no statistically significant difference between CABG and
medical therapy in patients with stable CAD and LV dysfunction, the long-term
follow-up at 10 years (STICHES) demonstrated that CABG did significantly decrease
death from any cause and all secondary outcomes. However, these pivotal trials
have focused solely on surgical revascularization. Comparable studies regarding
outcomes after contemporary PCI methods in this particular subset of patients are
severely lacking. More recent studies have included very small numbers of
patients with reduced EF. In conclusion, given advances in surgical and non
invasive fields, studies investigating long-term effects of PCI versus CABG,
including combined hybrid revascularization techniques are warranted. This review
sets the stage for a high-quality randomized, controlled trial comparing
revascularization with PCI versus CABG in patients with stable CAD and LV
dysfunction.
PMID- 28707393
TI - Malaria, Epstein-Barr virus infection and the pathogenesis of Burkitt's lymphoma.
AB - A geographical and causal connection has long been recognized between malaria,
Epstein-Barr virus (EBV) infection and Burkitt's lymphoma (BL), but the
underlying mechanisms remain obscure. Potential clues are that the malaria
parasite Plasmodium falciparum selectively absorbs vitamin A from the host and
depends on it for its biological activities; secondly, alterations in vitamin A
(retinoid) metabolism have been implicated in many forms of cancer, including BL.
The first author has proposed that the merozoite-stage malaria parasite, emerging
from the liver, uses its absorbed vitamin A as a cell membrane destabilizer to
invade the red blood cells, causing anemia and other signs and symptoms of the
disease as manifestations of an endogenous form of hypervitaminosis A (Mawson AR,
Path Global Health 2013;107(3):122-9). Repeated episodes of malaria would
therefore be expected to expose the tissues of affected individuals to
potentially toxic doses of vitamin A. It is proposed that such episodes activate
latent EBV infection, which in turn activates retinoid-responsive genes.
Expression of these genes enhances viral replication and induces germinal center
(GC) B cell expansion, activation-induced cytidine deaminase (AID) expression,
and c-myc translocation, which in turn predisposes to BL. Thus, an endogenous
form of retinoid toxicity related to malaria infection may be the common factor
linking frequent malaria, EBV infection and BL, whereby prolonged exposure of
lymphatic tissues to high concentrations of retinoids may combine to induce B
cell translocation and increase the risk of Burkitt's lymphoma.
PMID- 28707394
TI - CD19 regulates ADAM28-mediated Notch2 cleavage to control the differentiation of
marginal zone precursors to MZ B cells.
AB - As the first line of defence, marginal zone (MZ) B cells play principal roles in
clearing blood-borne pathogens during infection and are over-primed in autoimmune
diseases. However, the basic mechanisms underlying MZ B-cell development are
still unclear. We found here that CD19 deficiency blocked the differentiation of
marginal zone precursors (MZP) to MZ B cells, whereas CD19 expression in CD19
deficient MZP rescues MZ B-cell generation. Furthermore, CD19 regulates Notch2
cleavage by up-regulating ADAM28 expression in MZP. Finally, we found that CD19
suppressed Foxo1 expression to promote ADAM28 expression in MZP. These results
suggest that CD19 controls the differentiation of MZP to MZ B cells by regulating
ADAM28-mediated Notch2 cleavage. Thus, we demonstrated the basic mechanisms
underlying the differentiation of MZP to MZ B cells.
PMID- 28707395
TI - Association of pancreatic MRI R2* with blood glucose and cardiac MRI R2* among
thalassemia major patients in Indonesia.
PMID- 28707396
TI - Role of abnormal repolarization in the mechanism of cardiac arrhythmia.
AB - In cardiac patients, life-threatening tachyarrhythmia is often precipitated by
abnormal changes in ventricular repolarization and refractoriness. Repolarization
abnormalities typically evolve as a consequence of impaired function of outward
K+ currents in cardiac myocytes, which may be caused by genetic defects or result
from various acquired pathophysiological conditions, including electrical
remodelling in cardiac disease, ion channel modulation by clinically used
pharmacological agents, and systemic electrolyte disorders seen in heart failure,
such as hypokalaemia. Cardiac electrical instability attributed to abnormal
repolarization relies on the complex interplay between a provocative arrhythmic
trigger and vulnerable arrhythmic substrate, with a central role played by the
excessive prolongation of ventricular action potential duration, impaired
intracellular Ca2+ handling, and slowed impulse conduction. This review outlines
the electrical activity of ventricular myocytes in normal conditions and cardiac
disease, describes classical electrophysiological mechanisms of cardiac
arrhythmia, and provides an update on repolarization-related surrogates currently
used to assess arrhythmic propensity, including spatial dispersion of
repolarization, activation-repolarization coupling, electrical restitution, TRIaD
(triangulation, reverse use dependence, instability, and dispersion), and the
electromechanical window. This is followed by a discussion of the mechanisms that
account for the dependence of arrhythmic vulnerability on the location of the
ventricular pacing site. Finally, the review clarifies the electrophysiological
basis for cardiac arrhythmia produced by hypokalaemia, and gives insight into the
clinical importance and pathophysiology of drug-induced arrhythmia, with
particular focus on class Ia (quinidine, procainamide) and Ic (flecainide) Na+
channel blockers, and class III antiarrhythmic agents that block the delayed
rectifier K+ channel (dofetilide).
PMID- 28707397
TI - Response to Dr. Bain's comment on our review article: Pure Erythroid Leukemia.
PMID- 28707398
TI - Causes of early death in multiple myeloma patients treated with high-dose therapy
followed by autologous stem cell transplantation: A study based on the nationwide
Danish Multiple Myeloma Registry.
PMID- 28707399
TI - Neuroglobin and friends.
AB - In the year 2000, the third member of the globin family was discovered in human
and mouse brain and named neuroglobin (Ngb). Neuroglobin overexpression
significantly protects both heart and brain from hypoxic/ischemic and oxidative
stress-related insults, whereas decreased Ngb levels lead to an exacerbation of
tissue injuries. Moreover, Ngb overexpression protects neurons from mitochondrial
dysfunctions and neurodegenerative disorders such as Alzheimer disease; however,
it facilitates the survival of cancer cells. Neuroglobin, representing a switch
point for cell death and survival, has been reported to recognize a number of
proteins involved in several metabolic pathways including ionic homeostasis
maintenance, energy metabolism, mitochondrial function, and cell signaling. Here,
the recognition properties of Ngb are reviewed to highlight its roles in health
and disease.
PMID- 28707400
TI - Hormone factors play a favorable role in female head and neck cancer risk.
AB - Due to lower female incidence, estimates of exogenous and endogenous hormonal
factors in head and neck cancers (HNCs, comprising cancers of the oral cavity,
oropharynx, hypopharynx, and larynx) among women have been inconsistent and
unable to account for key HNC risk factors. We pooled data from 11 studies from
Europe, North America, and Japan. Analysis included 1572 HNC female cases and
4343 controls. Pooled odds ratios (ORs) estimates and their 95% confidence
intervals (CIs) were calculated using multivariate logistic regression models
adjusting for tobacco smoking and alcohol drinking. Lower risk was observed in
women who used hormone replacement therapy (HRT) (OR = 0.58; 95% CI: 0.34-0.77).
Pregnancy (OR = 0.61; 95% CI: 0.42-0.90) and giving birth (OR = 0.59; 95% CI:
0.38-0.90) at <35 years of age were inversely associated with HNCs. An inverse
association with HNC was observed with age at start of HRT use (OR = 0.59; 95%
CI: 0.39-0.90) for each additional 10 years and with duration of use (OR = 0.87;
95% CI: 0.76-0.99 for every 3 years). Exogenous female hormone use is associated
with a nearly twofold risk reduction in female HNCs. The lower female HNC
incidence may, in part, be explained by endogenous and exogenous estrogen
exposures.
PMID- 28707401
TI - Structural and functional diversity of EF-hand proteins: Evolutionary
perspectives.
AB - We have classified 865 sequences of EF-hand proteins from five proteomes into 156
subfamilies. These subfamilies were put into six groups. Evolutionary
relationships among subfamilies and groups were analyzed from the inferred
ancestral sequence for each subfamily. CTER, CPV, and PEF groups arose from a
common EF-lobe (pair of adjacent EF-hands). They have two or more EF-lobes; the
relative positions of their EF-lobes differ from each other. Comparisons of the
ancestral sequences and the inferred structures of the EF-lobes of these groups
indicate that the mutual positions of EF-lobes were established soon after
divergence of an EF-lobe for each group and before the duplication and fusion of
EF-lobe gene(s). These ancestral sequences reveal that some subfamilies in low
similarity and isolated groups did not evolve from the EF-lobe precursor, even if
their conformations are similar to the canonical EF-hand. This is an example of
convergent evolution.
PMID- 28707402
TI - Upper esophageal sphincter (UES) metrics on high-resolution manometry (HRM)
differentiate achalasia subtypes.
AB - BACKGROUND: The upper esophageal sphincter (UES) reflexively responds to bolus
presence within the esophageal lumen, therefore UES metrics can vary in
achalasia. METHODS: Within consecutive patients undergoing esophageal high
resolution manometry (HRM), 302 patients (58.2+/-1.0 year, 57% F) with esophageal
outflow obstruction were identified, and compared to 16 asymptomatic controls
(27.7+/-0.7 year, 56% F). Esophageal outflow obstruction was segregated into
achalasia subtypes 1, 2, and 3, and esophagogastric junction outflow obstruction
(EGJOO with intact peristalsis) using Chicago Classification v3.0. UES and lower
esophageal sphincter (LES) metrics were compared between esophageal outflow
obstruction and normal controls using univariate and multivariate analysis.
Linear regression excluded multicollinearity of pressure metrics that
demonstrated significant differences across individual subtype comparisons. KEY
RESULTS: LES integrated relaxation pressure (IRP) had utility in differentiating
achalasia from controls (P<.0001), but no utility in segregating between subtypes
(P=.27). In comparison to controls, patients collectively demonstrated univariate
differences in UES mean basal pressure, relaxation time to nadir, recovery time,
and residual pressure (UES-RP) (P<=.049). UES-RP was highest in type 2 achalasia
(P<.0001 compared to other subtypes and controls). In multivariate analysis, only
UES-RP retained significance in comparison between each of the subgroups (P<=.02
for each comparison). Intrabolus pressure was highest in type 3 achalasia; this
demonstrated significant differences across some but not all subtype comparisons.
CONCLUSIONS AND INFERENCES: Nadir UES-RP can differentiate achalasia subtypes
within the esophageal outflow obstruction spectrum, with highest values in type 2
achalasia. This metric likely represents a surrogate marker for esophageal
pressurization.
PMID- 28707403
TI - Melanocytic lesion evolution patterns with targeted therapies and immunotherapies
for advanced metastatic melanoma: An observational study.
AB - BACKGROUND/OBJECTIVES: Various cutaneous side-effects have been reported with
anti-melanoma systemic therapies. This study investigated the changes in
melanocytic lesion pigmentation in patients on four different therapies. METHODS:
We analysed the serial dermatoscopic photographs of atypical melanocytic lesions
taken from patients with advanced metastatic melanoma on four different systemic
therapies (selective BRAF-inhibitor monotherapy, dabrafenib combined with
trametinib [D&T], anti-programmed cell death protein 1 [anti-PD1] therapies, and
anti-PD1 combined with ipilimumab) seen from February 2013 to May 2016. We
compared these changes with the melanocytic lesions of 10 control patients.
RESULTS: In the control group, 19% of naevi lightened, 64% did not change and 17%
darkened. Only the BRAF inhibitor group showed more darkened lesions than
controls (37%, P < 0.001). Meanwhile, there were more lightened naevi in the D&T
therapy group (86%, P < 0.001) as well as the anti-PD1 and ipilimumab groups
(59%, P < 0.001) than controls. Patients on anti-PD1 monotherapy had more
lightened (49%) and fewer darkened naevi (9%) than controls, but differences were
not significant. CONCLUSIONS: Our study showed that different anti-melanoma
systemic therapies have different effects on the pigmentation of melanocytic
lesions. BRAF inhibitor may have the propensity to cause darkening while D&T
therapy and anti-PD1 caused lightening compared with controls. The findings
emphasise the importance of regular dermatological monitoring in specialised
clinics for patients on anti-melanoma systemic therapy. Clinicians should expect
changes in the global pigmentation of melanocytic lesions but be suspicious of
lesions with structural changes.
PMID- 28707404
TI - Sustained versus standard inflations during neonatal resuscitation to prevent
mortality and improve respiratory outcomes.
AB - BACKGROUND: At birth, infants' lungs are fluid-filled. For newborns to have a
successful transition, this fluid must be replaced by air to enable effective
breathing. Some infants are judged to have inadequate breathing at birth and are
resuscitated with positive pressure ventilation (PPV). Giving prolonged
(sustained) inflations at the start of PPV may help clear lung fluid and
establish gas volume within the lungs. OBJECTIVES: To assess the efficacy of an
initial sustained (> 1 second duration) lung inflation versus standard inflations
(<= 1 second) in newly born infants receiving resuscitation with intermittent
PPV. SEARCH METHODS: We used the standard search strategy of the Cochrane
Neonatal Review Group to search the Cochrane Central Register of Controlled
Trials (CENTRAL; 2017, Issue 1), MEDLINE via PubMed (1966 to 17 February 2017),
Embase (1980 to 17 February 2017), and the Cumulative Index to Nursing and Allied
Health Literature (CINAHL) (1982 to 17 February 2017). We also searched clinical
trials databases, conference proceedings, and the reference lists of retrieved
articles to identify randomised controlled trials and quasi-randomised trials.
SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs comparing
initial sustained lung inflation (SLI) versus standard inflations given to
infants receiving resuscitation with PPV at birth. DATA COLLECTION AND ANALYSIS:
We assessed the methodological quality of included trials using Cochrane
Effective Practice and Organisation of Care Group (EPOC) criteria (assessing
randomisation, blinding, loss to follow-up, and handling of outcome data). We
evaluated treatment effects using a fixed-effect model with risk ratio (RR) for
categorical data and mean, standard deviation (SD), and weighted mean difference
(WMD) for continuous data. We assessed the quality of evidence using the Grading
of Recommendations Assessment, Development, and Evaluation (GRADE) approach. MAIN
RESULTS: Eight trials enrolling 941 infants met our inclusion criteria.
Investigators in seven trials (932 infants) administered sustained inflation with
no chest compressions. Use of sustained inflation had no impact on the primary
outcomes of this review - mortality in the delivery room (typical RR 2.66, 95%
confidence interval (CI) 0.11 to 63.40; participants = 479; studies = 5; I2 not
applicable) and mortality during hospitalisation (typical RR 1.01, 95% CI 0.67 to
1.51; participants = 932; studies = 7; I2 = 19%); the quality of the evidence was
low for death in the delivery room (limitations in study design and imprecision
of estimates) and was moderate for death before discharge (limitations in study
design of most included trials). Amongst secondary outcomes, duration of
mechanical ventilation was shorter in the SLI group (mean difference (MD) -5.37
days, 95% CI -6.31 to -4.43; participants = 524; studies = 5; I2 = 95%; low
quality evidence). Heterogeneity, statistical significance, and magnitude of
effects of this outcome are largely influenced by a single study: When this study
was removed from the analysis, the effect was largely reduced (MD -1.71 days, 95%
CI -3.04 to -0.39, I2 = 0%). Results revealed no differences in any of the other
secondary outcomes (e.g. rate of endotracheal intubation outside the delivery
room by 72 hours of age (typical RR 0.93, 95% CI 0.79 to 1.09; participants =
811; studies = 5; I2 = 0%); need for surfactant administration during hospital
admission (typical RR 0.97, 95% CI 0.86 to 1.10; participants = 932; studies = 7;
I2 = 0%); rate of chronic lung disease (typical RR 0.95, 95% CI 0.74 to 1.22;
participants = 683; studies = 5; I2 = 47%); pneumothorax (typical RR 1.44, 95% CI
0.76 to 2.72; studies = 6, 851 infants; I2 = 26%); or rate of patent ductus
arteriosus requiring pharmacological treatment (typical RR 1.08, 95% CI 0.90 to
1.30; studies = 6, 745 infants; I2 = 36%). The quality of evidence for these
secondary outcomes was moderate (limitations in study design of most included
trials - GRADE) except for pneumothorax (low quality: limitations in study design
and imprecision of estimates - GRADE). AUTHORS' CONCLUSIONS: Sustained inflation
was not better than intermittent ventilation for reducing mortality in the
delivery room and during hospitalisation. The number of events across trials was
limited, so differences cannot be excluded. When considering secondary outcomes,
such as need for intubation, need for or duration of respiratory support, or
bronchopulmonary dysplasia, we found no evidence of relevant benefit for
sustained inflation over intermittent ventilation. The duration of mechanical
ventilation was shortened in the SLI group. This result should be interpreted
cautiously, as it can be influenced by study characteristics other than the
intervention. Future RCTs should aim to enrol infants who are at higher risk of
morbidity and mortality, should stratify participants by gestational age, and
should provide more detailed monitoring of the procedure, including measurements
of lung volume and presence of apnoea before or during the SLI.
PMID- 28707405
TI - Generation of biallelic F0 mutants in medaka using the CRISPR/Cas9 system.
AB - Several animal models generated by genome editing methods develop somatic mosaic
mutations including wild-type genome sequence in F0 generation because it is
difficult to use editing tools at the one-cell stage. Producing complete knockout
animals quickly is a great advantage in determining the function of target genes.
This study investigated the generation of F0 knockout medaka using the
CRISPR/Cas9 system. To determine whether this editing system induced mutations in
the medaka genome at the one-cell stage, recombinant Cas9 protein, tracrRNA and
crRNA for dead end (dnd), which is essential for germ cell development, were
injected into one-cell stage embryos of olvas-DsRedExpress transgenic medaka.
This allowed germ cells to be visualized by DsRed fluorescence. Genomic DNA
extracted from embryos at the one-cell stage was analyzed by sequencing.
Predictably, biallelic mutated sequence patterns in the target sites of dnd were
found in the injected embryos. To investigate the phenotypes of the mutated fish,
fluorescent and histological observations of germ cells were carried out using
fry and adults. The mutations resulted in a complete loss of germ cells,
suggesting loss of function of dnd in the injected embryos. Therefore, this
system appears to be extremely effective for the production of F0 knockout
medaka.
PMID- 28707406
TI - Quantitative efficacy of topical administration of tranexamic acid on
postoperative bleeding in total knee arthroplasty.
AB - AIMS: Topical tranexamic acid (TXA) is used in patients undergoing total knee
arthroplasty to reduce perioperative blood loss. However, the optimal dosing
regimen remains undetermined. The aim of the present study was to quantitatively
evaluate the effect of topical TXA on the reduction of postoperative drainage,
and identify the dosing regimen factors affecting the efficacy of topical TXA.
METHODS: Model-based meta-analysis was used to evaluate the efficacy of topical
TXA and the dosing regimen factors influencing clinical efficacy. Data from a
systemic literature search was identified and used to build a time-effect model
for placebo and TXA in treating perioperative blood loss. RESULTS: Fourteen
studies containing 16 TXA-control groups of drainage volume data were included
for MBMA modelling. The model described the postoperative drainage-time profiles
adequately. According to the model estimation, TXA can finally reduce the
postoperative drainage by about 41.7%, and 10.9 h was needed to reach 50% of the
maximal drainage volume. Covariate analysis indicated that both dose and contact
time alone did not correlate well with clinical efficacy. However, when
considered together, they can dramatically improve fitting of the data.
Simulation showed that increasing dose or contact time extensively would produce
a plateau-like effect: 2-3 g TXA with contact time of 1-2 h would yield >60%
reduction in the drainage volume. CONCLUSIONS: Dose and contact time together
determined the efficacy of TXA. Extensively large dose or long contact time seems
unnecessary. These findings may further guide the clinical practice on the
topical TXA regimen optimization.
PMID- 28707407
TI - Symptom fluctuations, self-esteem, and cohesion during group cognitive behaviour
therapy for early psychosis.
AB - : Group cohesion has been linked to positive changes in self-esteem and in
symptoms during group psychotherapy in people with psychosis. These changes may
be linked to changes in symptoms as fluctuations in self-esteem have been linked
to symptom fluctuations. OBJECTIVE: We aimed to determine the relationship
between these three factors - group cohesion, self-esteem, and symptoms - during
group cognitive behaviour therapy for psychosis (GCBTp). We hypothesized that
group cohesion would precede changes in symptoms and self-esteem and that
improvements in self-esteem would precede improvements in symptoms. DESIGN: This
is an uncontrolled longitudinal study recruiting from a convenience sample within
two early psychosis clinics. METHODS: Sixty-six individuals from first episode of
psychosis treatment programmes participated in this study and received 24
sessions of a validated GCBTp protocol. Participants answered a brief
questionnaire at the end of each session, measuring their group cohesion, self
esteem, and perception of their symptoms as worse, same, or better than usual.
RESULTS: Orthogonal polynomial contrasts for time effects were estimated with a
mixed model for repeated measures with a random cluster effect and revealed a
quartic trend regarding changes in symptoms over the 24 sessions. Self-esteem,
symptoms, and group cohesion were strongly linked during a given session. Also,
self-esteem changes predicted changes in symptoms up to two sessions later, and
symptoms changes predicted self-esteem changes at the next session. Group
cohesion preceded improvements in both self-esteem and symptoms; self-esteem also
predicted improvements in group cohesion. CONCLUSION: These results suggest that
self-esteem and symptoms influence each other during therapy, with improvements
in one leading to improvements in the other. Group cohesion also appears to be an
essential prerequisite to positive changes in self-esteem and symptoms during
GCBTp. PRACTITIONER POINTS: This study emphasizes the interrelation between self
esteem improvements and symptom improvements, with improvements in one leading to
improvements in the other, during group CBT for psychosis. Group cohesion, in
this study, is a predictor of self-esteem and symptom improvements, suggesting
that a special attention should be given to developing a strong alliance and
group cohesion early on during CBT for psychosis.
PMID- 28707408
TI - Complete heart block following transcatheter closure of perimembranous VSD using
amplatzer duct occluder II.
AB - Long term follow up studies have shown that transcatheter closure of
perimembranous Ventricular Septal Defect (PmVSD) can be done safely and
successfully. One of the most serious complications of VSD device closure is
complete atrioventricular block which has been reported in 3-18% is various
studies following VSD device closure. Amplatzar Duct Occluder II (ADO-II) device
is now commonly being used for closure of small to moderate sized PmVSD. Complete
heart block has not been reported with ADO-II device. We are reporting 2 cases of
complete heart block following transcatheter closure of PmVSD using ADO-II device
where sinus rhythm was established following early surgical removal of the
device.
PMID- 28707409
TI - Chilling-responsive DEMETER-LIKE DNA demethylase mediates in poplar bud break.
AB - Annual dormancy-growth cycle is a developmental and physiological process
essential for the survival of deciduous trees in temperate and boreal forests.
Seasonal control of shoot growth in woody perennials requires specific genetic
programmes responding to environmental signals. The environmental-controlled
mechanisms that regulate the shift between winter dormancy and the growth
promoting genetic programmes are still unknown. Here, we show that dynamics in
genomic DNA methylation levels are involved in the regulation of dormancy-growth
cycle in poplar. The reactivation of growth in the apical shoot during bud break
process in spring is preceded by a progressive reduction of genomic DNA
methylation in apex tissue. The induction in apex tissue of a chilling-dependent
poplar DEMETER-LIKE 10 (PtaDML10) DNA demethylase precedes shoot growth
reactivation. Transgenic poplars showing downregulation of PtaDML8/10 caused
delayed bud break. Genome-wide transcriptome and methylome analysis and data
mining revealed that the gene targets of DEMETER-LIKE-dependent DNA demethylation
are genetically associated with bud break. These data point to a chilling
dependent DEMETER-like DNA demethylase mechanisms being involved in the shift
from winter dormancy to a condition that precedes shoot apical vegetative growth
in poplar.
PMID- 28707410
TI - Treatment of an acquired Factor XIII inhibitor in an adolescent with systemic
lupus erythematosus and renal failure.
AB - BACKGROUND: Factor (F)XIII deficiency is a rare inherited bleeding disorder, but
can also be acquired due to the development of inhibitors. CASE REPORT: A 17-year
old female with systemic lupus erythematosus and end-stage kidney disease
secondary to Class IV lupus nephritis developed spontaneous subcutaneous and
muscular hematomas and delayed major bleeding after invasive procedures. She had
abnormal kaolin thromboelastography (kTEG; decreased maximal amplitude,
representative of clot strength) initially attributed to thrombocytopenia and
uremic platelet dysfunction, but her FXIII activity was undetectable, and a high
titer antibody against FXIII was identified. She had improvement in clinical
bleeding and in kaolin thromboelastogram result and transient improvement in
FXIII activity after each dose of plasma-derived FXIII concentrate (Corifact) or
cryoprecipitate. Her inhibitor titers gradually improved with multiple
immunosuppressive therapies and plasma exchange. While her FXIII activity level
remained mildly decreased, she has not had additional significant bleeding.
CONCLUSION: Treatment with either plasma-derived FXIII or cryoprecipitate is an
effective treatment to normalize the kTEG variables and clinical bleeding
diatheses associated with acquired FXIII inhibitors. Higher doses may be needed
in patients with high-titer inhibitor.
PMID- 28707411
TI - Quaternary 2D Transition Metal Dichalcogenides (TMDs) with Tunable Bandgap.
AB - Alloying/doping in 2D material is important due to wide range bandgap tunability.
Increasing the number of components would increase the degree of freedom which
can provide more flexibility in tuning the bandgap and also reduces the growth
temperature. Here, synthesis of quaternary alloys Mox W1-x S2y Se2(1-y) is
reported using chemical vapor deposition. The composition of alloys is tuned by
changing the growth temperatures. As a result, the bandgap can be tuned which
varies from 1.61 to 1.85 eV. The detailed theoretical calculation supports the
experimental observation and shows a possibility of wide tunability of bandgap.
PMID- 28707412
TI - Differences in the daily activity of patients with diabetic foot ulcers compared
to controls in their free-living environments.
AB - The aims of our study were to investigate multiple daily activity outcomes in
patients with diabetic foot ulcers (DFU) compared to diabetic peripheral
neuropathy (DPN) and diabetes (DM) controls in their free-living environments. We
examined daily activity outcomes of 30 patients with DFU, 23 DPN and 20 DM. All
patients wore a validated multi-sensor device for > 5 days (>22 hours per day) to
measure their daily activity outcomes: steps, energy expenditure (kJ), average
metabolic equivalent tasks (METs), physical activity (>3.0 METs) duration and
energy expenditure, lying duration, sleep duration and sleep quality. We found
that DFU patients recorded fewer median (interquartile ranges, IQR) daily steps
[2154 (1621-4324)] than DPN [3660 (2742-7705)] and DM [5102 (4011-7408)] controls
(P < 0.05). In contrast, DFU patients recorded more mean +/- SD daily energy
expenditure (kJ) (13 006 +/- 3559) than DPN (11 085 +/- 1876) and DM (11 491 +/-
1559) controls (P < 0.05). We found no other differences in daily activity
outcomes (P > 0.1). We conclude that DFU patients typically take fewer steps but
expend more energy during their normal daily activity than DPN and DM controls.
We hypothesise that the increased energy expenditure for DFU patients may be due
to wound healing or an inefficient gait strategy. Further investigations into
this energy imbalance in DFU patients may improve healing in future.
PMID- 28707413
TI - Bulk Bismuth as a High-Capacity and Ultralong Cycle-Life Anode for Sodium-Ion
Batteries by Coupling with Glyme-Based Electrolytes.
AB - Sodium-ion batteries (SIBs) have attracted great interest for large-scale
electric energy storage in recent years. However, anodes with long cycle life and
large reversible capacities are still lacking and therefore limiting the
development of SIBs. Here, a bulk Bi anode with surprisingly high Na storage
performance in combination with glyme-based electrolytes is reported. This study
shows that the bulk Bi electrode is gradually developed into a porous integrity
during initial cycling, which is totally different from that in carbonate-based
electrolytes and ensures facile Na+ transport and structural stability. The
achievable capacity of bulk Bi in the NaPF6 -diglyme electrolyte is high up to
400 mAh g-1 , and the capacity retention is 94.4% after 2000 cycles,
corresponding to a capacity loss of 0.0028% per cycle. It exhibits two flat
discharge/charge plateaus at 0.67/0.77 and 0.46/0.64 V, ascribed to the typical
two-phase reactions of Bi <-> NaBi and NaBi <-> Na3 Bi, respectively. The
excellent performance is attributed to the unique porous integrity, stable solid
electrolyte interface, and good electrode wettability of glymes. This interplay
between electrolyte and electrode to boost Na storage performance will pave a new
pathway for high-performance SIBs.
PMID- 28707414
TI - Nucleophosmin 1 (NPM1) mutations in chronic myelomonocytic leukemia and their
prognostic relevance.
PMID- 28707415
TI - Effect of ginkgo extract supplementation on in vitro rumen fermentation and
bacterial profiles under different dietary conditions.
AB - Ginkgo extract was applied to a batch culture study and evaluated for its
potential as a feed additive for ruminant animals under different forage-to
concentrate (F:C) ratios (1:9, 3:7, 5:5, 7:3 and 9:1). Rumen fluid was mixed with
respective diet and incubated at 39 degrees C for 24 h with and without ginkgo
extract (1.6% fruit equivalent in culture). Methane production was significantly
decreased by ginkgo extract, with the greatest reductions found in the 5:5
(41.9%) followed by the 7:3 ratios (36.7%). Total short chain fatty acid and
ammonia levels were not affected by ginkgo extract supplementation in any of the
five different diets. However, ginkgo extract increased propionate proportion and
decreased acetate proportion in all dietary conditions tested. The levels of
total bacteria, Ruminococcus flavefaciens, Ruminococcus albus and Fibrobacter
succinogenes were decreased by ginkgo extract. The levels of Selenomonas
ruminantium, Anaerovibrio lipolytica, Ruminobacter amylophilus, Succinivibrio
dextrinosolvens and Megasphaera elsdenii were increased by ginkgo extract
supplementation, possibly contributing to the higher propionate production. These
results suggest that rumen modulation by ginkgo extract can be achieved at a wide
range of F:C ratios with no adverse impact on feed digestion. Moreover, F:C
ratios of 5:5 and 7:3 may be optimal when methane mitigation is expected.
PMID- 28707416
TI - Engaging the Terminal: Promoting Halogen Bonding Interactions with Uranyl Oxo
Atoms.
AB - Engaging the nominally terminal oxo atoms of the linear uranyl (UO22+ ) cation in
non-covalent interactions represents both a significant challenge and opportunity
within the field of actinide hybrid materials. An approach has been developed for
promoting oxo atom participation in a range of non-covalent interactions, through
judicious choice of electron donating equatorial ligands and appropriately
polarizable halogen-donor atoms. As such, a family of uranyl hybrid materials was
generated based on a combination of 2,5-dihalobenzoic acid and aromatic,
chelating N-donor ligands. Delineation of criteria for oxo participation in
halogen bonding interactions has been achieved by preparing materials containing
2,5-dichloro- (25diClBA) and 2,5-dibromobenzoic acid (25diBrBA) coupled with 2,2'
bipyridine (bipy) (1 and 2), 1,10-phenanthroline (phen) (3-5), 2,2':6',2''
terpyridine (terpy) (6-8), or 4'-chloro-2,2':6',2''-terpyridine (Cl-terpy) (9
10), which have been characterized through single crystal X-ray diffraction,
Raman, Infrared (IR), and luminescence spectroscopy, as well as through density
functional calculations of electrostatic potentials. Looking comprehensively,
these results are compared with recently published analogues featuring 2,5
diiodobenzoic acid which indicate that although inclusion of a capping ligand in
the uranyl first coordination sphere is important, it is the polarizability of
the selected halogen atom that ultimately drives halogen bonding interactions
with the uranyl oxo atoms.
PMID- 28707417
TI - Defining the metal specificity of a multifunctional biofilm adhesion protein.
AB - The accumulation associated protein (Aap) of Staphylococcus epidermidis mediates
intercellular adhesion events necessary for biofilm growth. This process depends
upon Zn2+ -induced self-assembly of G5 domains within the B-repeat region of the
protein, forming anti-parallel, intertwined protein "ropes" between cells.
Pleomorphism in the Zn2+ -coordinating residues was observed in previously solved
crystal structures, suggesting that the metal binding site might accommodate
other transition metals and thereby support dimerization. By use of carefully
selected buffer systems and a specialized approach to analyze sedimentation
velocity analytical ultracentrifugation data, we were able to analyze low
affinity metal binding events in solution. Our data show that both Zn2+ and Cu2+
support B-repeat assembly, whereas Mn2+ , Co2+ , and Ni2+ bind to Aap but do not
support self-association. As the number of G5 domains are increased in longer B
repeat constructs, the total concentration of metal required for dimerization
decreases and the transition between monomer and dimer becomes more abrupt. These
characteristics allow Aap to function as an environmental sensor that regulates
biofilm formation in response to local concentrations of Zn2+ and Cu2+ , both of
which are implicated in immune cell activity.
PMID- 28707418
TI - Comparison of nutrient intake in adolescents and adults with and without food
allergies.
AB - BACKGROUND: Exclusion diets for the management of food allergy pose a risk of
nutritional deficiencies and inadequate growth in children, yet less is known
about their effect in adolescents and adults. The present study aimed to compare
the dietary intake of adolescents and adults with food allergies with that of a
control group. METHODS: A food allergic and a control group were recruited from
Portsmouth and the Isle of Wight in the UK. Participants were recruited from a
food allergy charity, allergy clinics, a local school and university, and
previous research studies. Macro and micronutrient intake data were obtained
using a 4-day estimated food diary. Sociodemographic and anthropometric data was
collected via a constructed questionnaire. RESULTS: This cross-sectional study
included 81 adolescents (48 food allergic and 33 controls) aged 11-18 years and
70 adults aged 19-65 years (23 food allergic and 47 controls). Overall, 19
(22.8%) adolescents and 19 (27.1%) adults took dietary supplements, with no
difference according to food allergic status. Adolescents with food allergy had
higher intakes of niacin and selenium than adolescents without (P < 0.05). This
difference persisted when dietary supplements were removed from the analysis.
Adults with food allergies had higher intakes of folate and zinc than those
without (P < 0.05); however, this difference did not persist when dietary
supplements were removed from the analysis. Across all participants, the intake
of several micronutrients was suboptimal. There was no difference in protein or
energy intake, or body mass index, according to food allergic status.
CONCLUSIONS: The dietary intake of food allergic participants was broadly similar
and, in some cases, better than that of control participants. However, suboptimal
intakes of several micronutrients were observed across all participants,
suggesting poor food choices.
PMID- 28707419
TI - Translation fidelity coevolves with longevity.
AB - Whether errors in protein synthesis play a role in aging has been a subject of
intense debate. It has been suggested that rare mistakes in protein synthesis in
young organisms may result in errors in the protein synthesis machinery,
eventually leading to an increasing cascade of errors as organisms age. Studies
that followed generally failed to identify a dramatic increase in translation
errors with aging. However, whether translation fidelity plays a role in aging
remained an open question. To address this issue, we examined the relationship
between translation fidelity and maximum lifespan across 17 rodent species with
diverse lifespans. To measure translation fidelity, we utilized sensitive
luciferase-based reporter constructs with mutations in an amino acid residue
critical to luciferase activity, wherein misincorporation of amino acids at this
mutated codon re-activated the luciferase. The frequency of amino acid
misincorporation at the first and second codon positions showed strong negative
correlation with maximum lifespan. This correlation remained significant after
phylogenetic correction, indicating that translation fidelity coevolves with
longevity. These results give new life to the role of protein synthesis errors in
aging: Although the error rate may not significantly change with age, the basal
rate of translation errors is important in defining lifespan across mammals.
PMID- 28707420
TI - Transthoracic intracardiac catheters in pediatric cardiac patients: A single
center experience.
AB - BACKGROUND: Transthoracic intracardiac catheters are frequently inserted in
children during congenital heart surgery for monitoring and vascular access
purposes. Their use entails a small potential risk. AIM: We aimed to evaluate
both catheter-associated morbidities related to maintenance and removal of
transthoracic intracardiac catheters in pediatric cardiac patients, and
predictors for catheter-associated adverse events. METHODS: Single-center
retrospective cohort study of prospectively collected data of children aged 0-14
years receiving a transthoracic intracardiac catheter inserted in the operating
room during 7 consecutive years at the University Children's Hospital Zurich.
RESULTS: A total of 115 transthoracic intracardiac catheters were placed in 112
patients: 45 right atrial, 68 left atrial, and 2 pulmonary artery catheters. Five
catheters (4.3%) had to be removed due to catheter-associated adverse events
(infection, 2; nonfunction, 2; and leakage 1). After catheter removal, 19% of
patients suffered adverse events, these were minor in 16 (14%) and serious in 6
(5.1%) (symptomatic bleeding in four (3.5%) patients, pericardial tamponade
leading to death in one (0.8%), and tension pneumothorax in one (0.8%)). Catheter
position in the right atrium and the need for platelet transfusion prior to
removal were risk factors for adverse events. CONCLUSIONS: Transthoracic
intracardiac catheters are useful in the management of specific patient groups
with complex congenital heart defects. Adverse events do occur; most of them do
not require intervention. The insertion technique plays an important role in
avoiding adverse events. Strict guidelines for the use and removal of
transthoracic intracardiac catheters are required. Low platelet count should
delay catheter removal. The wealth of information and therapeutic options offered
by these catheters appear to outweigh the associated potential adverse events in
this specific patient group.
PMID- 28707421
TI - Safer and more appropriate opioid prescribing: a large healthcare system's
comprehensive approach.
AB - RATIONALE, AIMS, AND OBJECTIVES: The United States is in the midst of a public
health epidemic with more than 40 people dying each day from prescription opioid
overdoses. Health care systems are taking steps to address the opioid overdose
epidemic by implementing policy and practice interventions to mitigate the risks
of long-term opioid therapy. Kaiser Permanente Southern California launched a
comprehensive initiative to transform the way that chronic pain is viewed and
treated. Kaiser Permanente Southern California created prescribing and dispensing
policies, monitoring and follow-up processes, and clinical coordination through
electronic health record integration. The purpose of this paper is to describe
the implementation of these interventions and assess the impact of this set of
interventions on opioid prescribing. METHOD: The study used a retrospective pre
post evaluation design to track outcomes before and after the intervention.
Kaiser Permanente Southern California members age 18 and older excluding cancer,
hospice, and palliative care patients and this sub-population of 3 203 880 was
approximately 75% of all Kaiser Permanente Southern California members. All data
are from Kaiser Permanente's pharmacy data systems and electronic health record
collected on a rolling basis as interventions were implemented from January 2010
to December 2015. RESULTS: There were reductions in all tracked outcomes: a 30%
reduction in prescribing opioids at high doses; a 98% reduction in the number of
prescriptions with quantities greater than 200 pills; a 90% decrease in the
combination of an opioid prescription with benzodiazepines and carisoprodol; a
72% reduction in the prescribing of Long Acting/Extended Release opioids; and a
95% reduction in prescriptions of brand name opioid-acetaminophen products. In
addition, methadone prescribing did not increase during this period. CONCLUSIONS:
This study adds promising results that a comprehensive system-level strategy has
the ability to positively affect opioid prescribing. The basic components of the
intervention are generalizable and applicable to other health care settings.
PMID- 28707422
TI - Description of D-glucosamine immobilization kinetics onto poly(lactic acid)
surface via a multistep physicochemical approach for preparation of novel active
biomaterials.
AB - Poly(lactic acid) (PLA) has shown much success in the preparation of tissue
engineering scaffolds as it can be fabricated with a tailored architecture.
However, the PLA surface has drawbacks including the lack of biofunctional motifs
which are essential for high affinity to biological cells. Therefore, this study
describes a multistep physicochemical approach for the immobilization of d
glucosamine (GlcN), a naturally occurring monosaccharide having many biological
functions, on the PLA surface aiming at enhancing the cell proliferation
activity. In this approach, poly(acrylic acid) (PAAc) spacer arms are first
introduced into the PLA surface via plasma post-irradiation grafting technique.
Then, covalent coupling or physical adsorption of GlcN with/on the PAAc spacer is
carried out. Factors affecting the grafting yield are controlled to produce a
suitable spacer for bioimmobilization. X-ray photon spectroscopic (XPS) analyses
confirm the immobilization of GlcN on the PLA surface. The XPS results reveal
also that increasing the yield of grafted PAAc spacer on the PLA surface
increases the amount of covalently immobilized GlcN, but actually inhibits the
immobilization process using the physical adsorption method. Contact angle
measurements and atomic force microscopy (AFM) show a substantial increase of
surface energy and roughness of PLA surface, respectively, upon the multistep
modification procedure. The cytocompatibility of the modified surfaces is
assessed using a mouse embryonic fibroblast (MEF) cell line. Observation from the
cell culture basically demonstrates the potential of GlcN immobilization in
improving the cytocompatibility of the PLA surface. Moreover, the covalent
immobilization of GlcN seems to produce more cytocompatible surfaces if compared
with the physical adsorption method. (c) 2017 Wiley Periodicals, Inc. J Biomed
Mater Res Part A: 105A: 3176-3188, 2017.
PMID- 28707423
TI - A universal drug delivery catheter for the treatment of infrapopliteal arterial
disease: Results from the multi-center first-in-human study.
AB - OBJECTIVE: The objective of this study was to assess the feasibility, safety and
initial efficacy of paclitaxel administration using a novel drug delivery
catheter for the prevention of restenosis in infrapopliteal de novo and
restenotic lesions. BACKGROUND: Restenosis continues to be a great challenge
after percutaneous revascularization procedures for peripheral arterial disease,
particularly for below-the-knee applications. METHODS: A prospective, multicenter
first-in-human registry of a novel delivery catheter delivering liquid paclitaxel
was conducted in 10 patients. The primary efficacy endpoint at 6 months was
freedom from clinically driven target lesion revascularization (CD-TLR) and the
primary safety endpoint at 1, 3, and 6 months were thrombosis, major amputation
in the target limb and target limb related death. RESULTS: All patients tolerated
the procedure well with no reports of adverse procedural events. Twelve (n = 12)
lesions in ten patients were treated with a mean lesion length of 83.3 +/- 49.2
mm, with the lesion length range of 30mm to 182 mm. At 6-month follow-up, the
rate of CD-TLR was 30% (3 of 10 patients). Zero patients (0 out of 10)
demonstrated thrombosis, major amputation in the target limb and target limb
related death at the 1, 3, and 6 month follow-up intervals. CONCLUSIONS: This
first in-human experience obtained in a multicenter study of real-world de novo
and restenotic lesions demonstrates a favorable safety and efficacy profile at 6
months. Randomized comparison to current drug coated balloons should be performed
to further validate this approach and positive experience.
PMID- 28707424
TI - A reproducible microcosm biofilm model of subgingival microbial communities.
AB - OBJECTIVE: To develop a reproducible subgingival microcosm biofilm model.
MATERIAL AND METHODS: Subgingival plaque samples were collected from four deep
pockets (probing pocket depth >=6 mm) in each of seven patients with
periodontitis and from shallow pockets (probing pocket depth <=3 mm) in two
periodontally healthy donors. An active attachment model and a peptone medium
(Thompson et. al., Appl Environ Microbiol 2015;81:8307-8314) supplemented with
30% serum was used. Biofilms were harvested at 2 and 4 weeks. DNA of dead cells
was blocked for amplification by propidium monoazide treatment. Composition was
analyzed using 16S rRNA gene amplicon pyrosequencing. Similarities between the
biofilm samples were assessed by non-metric multidimensional scaling using the
Bray-Curtis similarity index and similarity percentage analysis. Data from
duplicate experiments, different biofilm sources and different biofilm age were
compared. RESULTS: The non-metric multidimensional scaling revealed a strong
clustering by the inoculum source, the donor and their periodontal status.
Statistically significant differences were found between the sources of inoculum
(P=.0001) and biofilm age (P=.0016). Furthermore, periodontitis biofilms (P) were
distinct in composition from health-derived biofilms (H) by genera: Porphyromonas
(P=19%; H=0%), Filifactor (P=10%; H=0%), Anaeroglobus (P=3%; H=0%), Phocaeicola
(P=1.5%; H=0%), Parvimonas (P=19%; H=14%), Fusobacterium (P=2%; H=26%),
Peptostreptococcus (P=20%; H=30%), Veillonella (P=7%; H=8%) and 57 other genera.
Similarity distances (Bray-Curtis) (mean 0.73, SD 0.15) and the Shannon diversity
index (mean 2, SD 0.2) revealed no differences between duplicate experiments
(P=.121). CONCLUSION: This biofilm model allows reproducible production of
complex subgingival microbial communities.
PMID- 28707425
TI - Experiential acceptance and trait-mindfulness as predictors of analogue post
traumatic stress.
AB - OBJECTIVES: Experiential acceptance and trait-mindfulness are associated with
post-traumatic stress disorder (PTSD) after traumatic events. This study was a
preliminary attempt to examine (1) associations of experiential acceptance and
trait-mindfulness with post-traumatic stress (PTS) associated with negative, but
not necessarily traumatizing, life events ('analogue' PTS), (2) the role of these
variables in the context of neuroticism as well as worry and rumination - two
other regulatory strategies associated with PTS, and (3) the impact of pre-trauma
tendencies towards experiential acceptance and mindfulness on analogue PTS.
DESIGN: Data were obtained from two distinct student samples. A first sample
provided cross-sectional data. In a second sample, indices of acceptance,
mindfulness, neuroticism, worry, and rumination were tapped at inclusion into the
study, and analogue PTS and confrontation with stressful life events were
subsequently assessed 1 year later. RESULTS: In the cross-sectional sample,
higher acceptance and mindfulness were associated with lower analogue PTS, even
when controlling for neuroticism, worry, and rumination. In the prospective
sample, pre-trauma mindfulness (but not experiential acceptance, neuroticism,
worry, and rumination) assessed at baseline predicted levels of analogue PTS 1
year later. CONCLUSIONS: Findings suggest that experiential acceptance and trait
mindfulness are incrementally related to PTS beyond neuroticism, worry, and
rumination and that pre-trauma trait-mindfulness may be a resilience factor
protecting against severe PTS. PRACTITIONER POINTS: We examined associations of
experiential acceptance and trait-mindfulness with post-traumatic stress (PTS)
associated with negative life events ('analogue' PTS). Experiential acceptance
and trait-mindfulness were associated with concurrent analogue PTS, over and
above neuroticism, worry, and rumination. Pre-trauma trait-mindfulness (but not
pre-trauma experiential acceptance) significantly predicted analogue PTS in
prospective analyses. Enhancing mindfulness skills could be a useful tool to
reduce the risk of PTS in trauma-exposed samples.
PMID- 28707426
TI - Influence of neighbourhood safety on childhood obesity: a systematic review and
meta-analysis of longitudinal studies.
AB - Unsafe residential neighbourhoods are thought to be a risk factor for childhood
obesity by discouraging physical activity while encouraging sedentary behaviours,
but findings from cross-sectional studies are susceptible to selection bias (e.g.
children who are obese disproportionately reside in unsafe neighbourhoods). A
literature search was conducted in the Cochrane Library, PubMed, Web of Science
and Google Scholar for articles published until January 2017 that used baseline
neighbourhood safety levels to predict future weight-related behaviours and body
weight status among children aged 17 years and younger. Twenty-two prospective
cohort studies conducted in seven countries were identified. The median sample
size was 1,104, and the median follow-up was 3.5 years. Sixteen studies used
parent-reported and/or child-reported neighbourhood safety measures, and six
adopted some objective measures (e.g. county crime rate and interviewers' block
observations). The meta-analysis found that living in unsafe neighbourhoods was
associated with a reduction in children's physical activity by 0.13 h week-1 .
Living in unsafe neighbourhoods predicted a trivial (but statistically
significant) gain in body mass index but no change in childhood
overweight/obesity risk. Current research indicates a limited influence of
neighbourhood safety on childhood obesity; this finding could be partially due to
measurement problems. Future longitudinal studies should adopt validated
neighbourhood safety measures.
PMID- 28707427
TI - Time-dependent and nonlinear effects of prognostic factors in nonmetastatic
colorectal cancer.
AB - The survival risk following curative surgery for nonmetastatic colorectal cancer
(CRC) may be over- or underestimated due to a lack of attention to nonlinear
effects and violation of the proportional hazards assumption. In this paper, we
aimed to detect and interpret the shape of time-dependent and nonlinear effects
to improve the predictive performance of models of prognoses in nonmetastatic CRC
patients. Data for nonmetastatic CRC patients diagnosed between 2004 and 2012
were obtained from the Surveillance Epidemiology End Results registry. Time
dependent and nonlinear effects were tested and plotted. A nonlinear model that
used random survival forests was implemented. The estimated 5-year cancer
specific death rate was 17.95% (95% CI, 17.70-18.20%). Tumor invasion depth,
lymph node status, age at diagnosis, tumor grade, histology and tumor site were
significantly associated with cancer-specific death. Nonlinear and time-dependent
effects on survival were detected. Positive lymph node number had a larger effect
per unit of measurement at low values than at high values, whereas age at
diagnosis showed the opposite pattern. Moreover, nonproportional hazards were
detected for all covariates, indicating that the contributions of these risks to
survival outcomes decreased over time. The nonlinear model predicted prognoses
more accurately (C-index: 0.7934, 0.7933-0.7934) than did the Fine and Gray model
(C-index: 0.7550, 0.7510-0.7583). The three-dimensional cumulative incidence
curves derived from nonlinear model were used to identify the change points of
the risk trends. It would be useful to implement these findings in treatment
plans and follow-up surveillance in nonmetastatic CRC patients.
PMID- 28707428
TI - Identification of a novel allele, HLA-C*01:135, by full-length genomic
sequencing.
AB - The HLA-C*01:135 allele differs by a single nucleotide at codon 265 compared with
HLA-C*01:02:01:01.
PMID- 28707429
TI - Clinical significance of prothrombin G20210A mutation in homozygous patients.
PMID- 28707430
TI - Multi-genic pattern found in rare type of hypopituitarism: a whole-exome
sequencing study of Han Chinese with pituitary stalk interruption syndrome.
AB - Pituitary stalk interruption syndrome (PSIS) is a rare type of hypopituitarism
manifesting various degrees of pituitary hormone deficiency. Although mutations
have been identified in some familial cases, the underpinning mechanisms of
sporadic patients with PSIS who are in a vast majority remain elusive,
necessitating a comprehensive study using systemic approaches. We postulate that
other genetic mechanisms may be responsible for the sporadic PSIS. To test this
hypothesis, we conducted a study in 24 patients with PSIS of Han Chinese with no
family history using whole-exome sequencing (WES) and bioinformatic analysis. We
identified a group of heterozygous mutations in 92% (22 of 24) of the patients,
and these genes are mostly associated with Notch, Shh, Wnt signalling pathways.
Importantly, 83% (20 of 24) of the patients had more than one mutation in those
pathways suggesting synergy of compound mutations underpin the pathogenesis of
sporadic PSIS.
PMID- 28707431
TI - Efficacy of a Proprietary Trigonella foenum-graecum L. De-Husked Seed Extract in
Reducing Menopausal Symptoms in Otherwise Healthy Women: A Double-Blind,
Randomized, Placebo-Controlled Study.
AB - Trigonella foenum-graecum seed extract has demonstrated hormone modulatory
activity, providing biological plausibility for relieving menopausal symptoms.
The study aimed to assess efficacy of a standardized T. foenum-graecum de-husked
seed extract in reducing menopausal symptoms in healthy aging women. The study
was a double-blind, randomized, placebo-controlled trial that recruited 115 women
aged 40 to 65 years of which 59 were allocated to active (n = 54 completed) and
56 to placebo (n = 50 completed). Active treatment was T. foenum-graecum de
husked seed extract, 600 mg per day for 12 weeks. Outcome measures included
Menopause-Specific Quality of Life (MENQOL) questionnaire, frequency of hot
flushes and night sweats and serum estradiol levels. There was a significant
reduction in menopausal symptoms in the active group compared with placebo as
assessed by total MENQOL score (p < 0.001); reflected by significant improvements
in the vasomotor (p < 0.001), psychosocial (p < 0.001), physical (p < 0.001) and
sexual symptoms (p < 0.001) domains. Vasomotor outcomes correlated with hot
flushes, the active group reporting significantly less daytime hot flushes and
night sweats at 12 weeks (p < 0.001). The average estradiol levels were similar
in both the active group and placebo group after treatment. This study
demonstrated that this proprietary T. foenum-graecum de-husked seed extract may
reduce menopausal symptoms in healthy women. Copyright (c) 2017 John Wiley &
Sons, Ltd.
PMID- 28707432
TI - Mechanisms of breast cancer risk in shift workers: association of telomere
shortening with the duration and intensity of night work.
AB - Occupational factors such as shiftwork and especially night work that involves
disruption of the circadian rhythm may contribute to increased breast cancer
risk. Circadian disruption may also affect telomere length (TL). While short TL
generally is associated with increased cancer risk, its association with breast
cancer risk is inconclusive. We suggest that working schedules might be an
important factor in assessment of effects of TL on breast cancer risk. Moreover,
telomere shortening might be a potential mechanism for night work-related breast
cancer. In this study, effects of shift work on TL and its association with
breast cancer risk were investigated in a nested breast cancer case-control study
of Norwegian nurses. TL was assessed by qPCR in DNA from 563 breast cancer
patients and 619 controls. Here, we demonstrate that TL is affected by intensive
night work schedules, as work with six consecutive night for a period of more
than 5 years was associated with decreased telomere lengths (-3.18, 95% CI: -6.46
to -0.58, P = 0.016). Furthermore, telomere shortening is associated with
increased breast cancer risk in workers with long periods of consecutive night
shifts. Thus, nurses with longer telomere lengths had a lower risk for breast
cancer if they had worked more than four (OR: 0.37, 95% CI: 0.16-0.79, P = 0.014)
or five (OR: 0.31, 95% CI: 0.10-0.83, P = 0.029) consecutive night shifts for a
period of 5 years or more. These data suggest that telomere shortening is
associated with the duration and intensity of night work and may be a
contributing factor for breast cancer risk among female shift workers.
PMID- 28707433
TI - Comparison of irinotecan/platinum versus etoposide/platinum chemotherapy for
extensive-stage small cell lung cancer: A meta-analysis.
AB - This meta-analysis was performed to compare the effects and toxicities between
irinotecan/platinum (IP) and etoposide/platinum (EP) regimens as the fist-line
treatment of patients with extensive-stage small cell lung cancer (E-SCLC). A
systematic search was made of MEDLINE, Cochrane, ISI Web of Science and SCOPUS
databases. Randomised clinical trials on treatment of E-SCLC with the IP
regimens, compared with EP regimens, were reviewed. Studies were pooled to hazard
ratio (HR), relative risk (RR) and odds ratio (OR), with 95% confidence interval
(CI). Eight trials (enrolling 2089 participants) met the inclusion criteria.
Overall survival (OS) and 1-year survival rate were superior in the IP group (HR
0.83; 95% CI 0.75 to 0.91 and RR 1.19; 95% CI 1.06 to 1.34). Grades 3 and 4
anaemia, leukopenia, neutropenia, thrombocytopenia and febrile neutropenia were
less frequent in the IP regimens than that in the EP regimens. And grades 3 and 4
nausea/vomiting, diarrheal, anorexia and fatigue were less frequent in the EP
regimens. IP combination chemotherapy achieved a superior OS and 1-year survival
rate, compared with EP doublets, in patients with E-SCLC.
PMID- 28707434
TI - Utility of digital subtraction angiography-based collateral evaluation in
medically treated acute symptomatic basilar artery stenosis.
AB - BACKGROUND AND PURPOSE: Although a stroke from atherosclerosis in the basilar
artery (BA) often presents with mild initial stroke severity, it has
heterogeneous clinical courses. We investigated the efficacy of digital
subtraction angiography (DSA)-based collateral perfusion evaluation in
association with long-term outcomes of medically treated symptomatic basilar
artery stenosis. METHODS: From a registry database of all consecutive patients
with stroke, we included 98 medically treated patients (due to mild initial
stroke severity) [National Institute of Health Stroke Scale (NIHSS) scores <= 4;
symptomatic basilar artery stenosis, 70-99%] with available initial diagnostic
DSA. Basilar collateral scoring was performed via the DSA, using a modified
version of the American Society of Interventional and Therapeutic
Neuroradiology/Society of Interventional Radiology grading system in both the
superior cerebellar artery and anterior/posterior-inferior cerebellar artery
territories (score 0-8). The outcomes were designated as the 90-day modified
Rankin Scale (mRS90) score (poor, 3-6). Student's t-test, chi-square test and
logistic regression analyses were used to identify factors associated with a poor
outcome. RESULTS: The median initial NIHSS score was 2 [interquartile range
(IQR), 0-3], median posterior circulation Alberta Stroke Program Early CT Score
was 8 (IQR, 7-10), median collateral score was 7 (IQR, 7-8) and 20 (20.4%) had
poor mRS90 scores. In multivariate analysis, poorer collateral scores (P =
0.003), higher NIHSS scores (P = 0.005) and lower posterior circulation Alberta
Stroke Program Early CT Score (P = 0.017) were independently associated with a
poor mRS90 score. CONCLUSIONS: The DSA-based collateral scoring of the BA large
branches might predict long-term outcome in medically treated symptomatic basilar
artery stenosis with mild initial severity. Evaluation of BA collateral perfusion
status might be useful to determine appropriate treatment strategies.
PMID- 28707435
TI - Evidence-based policy choices for efficient and equitable cervical cancer
screening programs in low-resource settings.
AB - Women in developing countries disproportionately bear the burden of cervical
cancer. The availability of prophylactic vaccines against human papillomavirus
(HPV) types 16 and 18, which cause approximately 70% of cervical cancers,
provides reason for optimism as roll-out begins with support from Gavi, the
Vaccine Alliance. However, for the hundreds of millions of women beyond the
target age for HPV vaccination, cervical cancer screening to detect and treat
precancerous lesions remains the only form of prevention. Here we describe the
challenges that confront screening programs in low-resource settings, including
(1) optimizing screening test effectiveness; (2) achieving high screening
coverage of the target population; and (3) managing screen-positive women. For
each of these challenges, we summarize the tradeoffs between resource utilization
and programmatic attributes. We then highlight opportunities for efficient and
equitable programming, with supporting evidence from recent mathematical modeling
analyses informed by data from the PATH demonstration projects in India,
Nicaragua, and Uganda.
PMID- 28707436
TI - Pure erythroid leukemia: The need gather data on this condition as defined in the
World Health Organization classification.
PMID- 28707437
TI - Long-term impact of the low-FODMAP diet on gastrointestinal symptoms, dietary
intake, patient acceptability, and healthcare utilization in irritable bowel
syndrome.
AB - BACKGROUND: The low-FODMAP diet is a frequently used treatment for irritable
bowel syndrome (IBS). Most research has focused on short-term FODMAP restriction;
however, guidelines recommend that high-FODMAP foods are reintroduced to
individual tolerance. This study aimed to assess the long-term effectiveness of
the low-FODMAP diet following FODMAP reintroduction in IBS patients. METHODS:
Patients with IBS were prospectively recruited to a questionnaire study following
completion of dietitian-led low-FODMAP education. At baseline and following
FODMAP restriction (short term) only, gastrointestinal symptoms were measured as
part of routine clinical care. Following FODMAP reintroduction, (long term),
symptoms, dietary intake, acceptability, food-related quality of life (QOL), and
healthcare utilization were assessed. Data were reported for patients who
continued long-term FODMAP restriction (adapted FODMAP) and/or returned to a
habitual diet (habitual). KEY RESULTS: Of 103 patients, satisfactory relief of
symptoms was reported in 12% at baseline, 61% at short-term follow-up, and 57% at
long-term follow-up. At long-term follow-up, 84 (82%) patients continued an
'adapted FODMAP' diet (total FODMAP intake mean 20.6, SD 14.9 g/d) compared with
19 (18%) of patients following a 'habitual' diet (29.4, SD 22.9 g/d, P=.039).
Nutritional adequacy was not compromised for either group. The 'adapted FODMAP'
group reported the diet cost significantly more than the 'habitual' group
(P<.001) and affected social eating (P<.01) but there was no effect on food
related QOL. Healthcare utilization was similar between both groups. CONCLUSION
AND INFERENCES: Low-FODMAP education is effective for long-term IBS management,
enables a nutritionally adequate diet, and is broadly acceptable to patients.
PMID- 28707438
TI - Long term impact of the endocrine disruptor tributyltin on male fertility
following a single acute exposure.
AB - Declining rate of human fertility is a growing concern, where lifestyle and
environmental factors play an important role. We recently demonstrated that
tributyltin (TBT), an omnipresent endocrine disruptor, affects testicular cells
in vitro. In this study, male Wistar rats were gavaged a single dose of 10, 20,
and 30 mg/kg TBT-chloride (TBTC) (to mimic accidental exposure in vivo) and
sacrificed on day 3 and day 7, respectively. TBT bioavailability was evaluated by
estimating total tin content, and essential metal levels were analyzed along with
redox molecules (ROS and GSH/GSSG) to understand the effect on physiological
conditions. Blood-testicular barrier (BTB) disruption, levels of associated
proteins and activity of proteolytic enzymes were evaluated to understand the
effect on BTB. Histological analysis of tissue architecture and effect on protein
expression of steroidogenic, stress and apoptotic markers were also evaluated.
Widespread TBTC pollution can be an eventual threat to male fertility worldwide.
PMID- 28707439
TI - The Value of Independent Specialty Designation for Interventional Cardiology.
DOI: 10.1002/ccd.26656.
PMID- 28707440
TI - Everolimus eluting bioresorbable vascular scaffolds; can we absorb the risk in
complex PCI?
AB - BVS, as compared with DES, have higher stent thrombosis (ST) rates. BVS may prove
reasonable in patients with complex anatomy. Future trials will be necessary to
guide clinicians regarding whether BVS are equivalent to DES in patients with
noncomplex or complex coronary anatomy.
PMID- 28707441
TI - The importance of vision.
AB - Based on a systematic review and meta-analysis of 8 studies, involving 2,559
subjects, both interventional cardiologists (3.21) and cardiac cath lab staff
(2.76) had a significantly higher relative risk of posterior lens opacity than
the control group. It is essential to provide "best practice" in radiation dose
management and lead shielding in the cath lab with the standard "As Low As
Reasonably Achievable"! There is a clear need for better data to quantitate the
radiation risk and to design innovative strategies to decrease that risk.
PMID- 28707442
TI - Paravalvular leak versus need for permanent pacemaker after TAVR: Sailing between
Scylla and Charybdis.
AB - Absence or minimization of PVL after TAVR and its potential association with
higher rates of PPM placement has been the Achilles' heel of TAVR procedures. Pre
existing RBBB and depth of implantation are independent predictors of PPM need
after Lotus valve implantation. Optimization of device design, increased operator
experience, and focus on accurate device placement seem to result in decreased
need for PPM after Lotus valve implantation.
PMID- 28707443
TI - Cardiac transplant vasculopathy.
AB - Transplant vasculopathy is a form of slowly progressive rejection. The
interventional cardiologist plays an important role in maintaining survival of
this precious commodity by performing PCI. Everolimus drug eluting stents are
highly effective and have relatively low occurrence of in-stent restenosis, but
transplant vasculopathy continues to progress in a diffuse pattern.
PMID- 28707444
TI - Current approaches to retroperitoneal hemorrhage: Too little, too late.
AB - Retroperitoneal hemorrhage (RPH) arises in < 0.5% of patients undergoing
percutaneous intervention, but is associated with high risks of morbidity and
mortality. More than 50% of medical malpractice claims against interventional
cardiologists are related to death and hemorrhage from vascular injury; delays in
diagnosis and treatment are common. The current approach to RPH is characterized
by "too little" to diagnose and "too late" to manage patients in extremis.
Immediate CTA allows rapid diagnosis and triage to appropriate endovascular
therapy, without delay.
PMID- 28707445
TI - Angiographic and clinical outcome after crush of everolimus-eluting stent for
distal unprotected left main disease.
AB - : Obiectives: Angiographic and clinical outcomes after crushing of everolimus
eluting stent (EES) for distal unprotected left main disease (ULMD). BACKGROUND:
Few data exist about crushing of EES for distal ULMD. METHODS: From the Florence
ULMD Percutaneous Coronary Interevention Registry consecutive patients with
distal ULMD treated with EES were included in the analysis. Patients treated with
provisional stenting were compared with patients treated with crush stenting.
ENDPOINTS: angiographic in-segment restenosis rate, and 1-year clinical outcome.
RESULTS: From 2008 to 2015, 405 patients with distal ULMD were treated with EES:
278 (69%) were treated with provisional stenting while 127 (31%) with crush
stenting. Provisional stenting group compared to crush stenting group had higher
incidence of acute coronary syndrome on admission (63% vs. 52%; P = 0.033) and of
left ventricular ejection fraction <= 40% (36% vs. 23%; p= 0.008), while patients
treated with crush stenting had more frequently diabetes mellitus (35% vs. 21%; P
= 0.003) and 3-vessel coronary artery disease (46% vs. 29%; P < 0.001).
Angiographic follow rate was 95%. Restenosis rates were similar: 7.1% in the
crush stenting group and 5.8% in the provisional stenting group. There were no
differences in 1-year clinical outcome between crush stenting group and
provisional stenting group: major adverse cardiac events 11.1% and 11.2%, stent
thrombosis 0.8% and 1.4%, respectively. CONCLUSION: Crush stenting using EES in
patients with complex distal ULMD is associated with low rates of restenosis and
adverse clinical events and could be considered as a valid double stenting
technique in all patients with complex ULMD bifurcation lesions. (c) 2017 Wiley
Periodicals, Inc.
PMID- 28707446
TI - Percutaneous coronary intervention after a surgeon says, "no way".
AB - The rate of surgical turndowns (1.5-2.5%) in this report that went on to PCI is
relatively consistent across centers. Unprotected left main intervention in
patients turned down for surgery has high hospital mortality. With certain
caveats, the HEART Team approach to these unique patients may be the answer.
PMID- 28707447
TI - CTO revascularization: Obstacles and options in balloon nonpenetrable lesions.
AB - CTO lesions resisting balloon crossing are located in moderate/severe tortuous
coronary arteries contain more moderate/severe calcification burden and carry a
higher J-CTO score as compared with balloon crossable CTO lesions. CTO lesions
resisting balloon crossing do not constitute a homogenous group. In 25% of the
patients, the resisting CTO was caused by stent restenosis and thrombus is an
integral component of CTO in addition to calcium and fibrosis. The excimer laser
and rotational/orbital atherectomy are among useful debulking technologies
capable of creating a "pilot recanalization channel" in the CTO that enables
completion of the revasularization.
PMID- 28707448
TI - Left Main Coronary Angioplasty of a 9-Year-Old Child With Bioresorable Vascular
Scaffold. DOI: 10.1002/ccd.26896.
PMID- 28707449
TI - Individualizing dual antiplatelet therapy duration: Prediction tools, genomics,
and clinical judgment.
AB - Prolonged dual antiplatelet therapy (DAPT) after percutaneous coronary
intervention (PCI) on average reduces the risk of subsequent myocardial
infarction (MI) but increases major bleeds. Individualizing duration of DAPT
based on the DAPT trial's net benefit prediction tool would likely optimize
outcome beyond population average recommendations. Individualizing agent
selection and duration of therapy based on genomic data may further improve
outcomes. Clinical judgment remains the most important tool to tailor DAPT
duration based on a large array of additional relevant factors not captured by
predition rules or genomics.
PMID- 28707450
TI - A simple concept for covering pressure sores: wound edge-based propeller
perforator flap.
AB - We present a new surgical modification to allow propeller perforator flaps to
cover pressure sores at various locations. We used a propeller perforator flap
concept based on the detection of newly formed perforator vessels located 1 cm
from the wound margin and stimulated by the chronic inflammation process. Between
January 2009 and January 2017, 33 wound edge-based propeller perforator flaps
were used to cover pressure sores at various locations in 28 patients. In four
cases more than one flap was used on the same patient. The patients comprised 18
males and 10 females with a mean age of 41.25 (range, 16-70) years. All patients
underwent follow-up for 0-12 months. The mean follow-up duration was 5.03 months.
Venous congestion was observed in three flaps that were rotated by 180 degrees
(9.1%). However, there was a significant difference between flaps rotated by 90
degrees and 180 degrees according to the complication rate (P = 0.034). Out of
33 flaps, 29 flaps healed uneventfully. Patients were able to sit and lie on
their flaps three weeks after surgery. In our study, we were able to obtain
satisfying final results using these novel flaps.
PMID- 28707451
TI - Perceptions of key participants about Botswana adolescents' risks of unplanned
pregnancy, sexually transmitted diseases, and HIV: Qualitative findings.
AB - AIM: The qualitative research findings are reported on the perceptions of key
participants in Botswana about adolescent sexuality problems and the feasibility
(with suggestions) of an adolescent prevention intervention. METHODS: Twenty
adult key participants who were selected through purposive sampling from schools
and youth centers responded to open-ended questions during face-to-face
individual in-depth interviews that were conducted between December, 2011 and
January, 2012 in Gaborone, Botswana. RESULTS: The data were analyzed by using an
inductive content analysis. Five major themes and 12 subthemes emerged from the
interviews. The key participants discussed situations that exposed adolescents to
HIV, sexually transmitted infections, and pregnancy. They also discussed unsafe
sexual practices, the consequences of unprotected sex, poor parent-adolescent
communication on sexuality, and the need for a sexuality education program.
CONCLUSION: Policy changes are needed to improve collaboration between
adolescents, parents, teachers, and youth officers in order to address adolescent
sexuality problems. Further research is needed to explore the ways in which to
improve sexuality communication between these groups. The results of the study
provide valuable information on the sexuality risks that expose adolescents to
HIV, pregnancy, and sexually transmitted infections and the strategies for the
prevention of these risks, thus informing targeted interventions for risk
reduction for adolescents.
PMID- 28707452
TI - On the Dimensional Control of 2 D Hybrid Nanomaterials.
AB - Thermotropic smectic liquid crystalline polymers were used as a scaffold to
create organic/inorganic hybrid layered nanomaterials. Different polymers were
prepared by photopolymerizing blends of a hydrogen bonded carboxylic acid
derivative and a 10 % cross-linker of variable length in their liquid crystalline
phase. Nanopores with dimensions close to 1 nm were generated by breaking the
hydrogen bonded dimers in a high pH solution. The pores were filled with
positively charged silver (Ag) ions, resulting in a layered silver(I)-polymeric
hybrid material. Subsequent exposure to a NaBH4 reducing solution allowed for the
formation of supported hybrid metal/organic films. In the bulk of the film the
dimension of the Ag nanoparticles (NPs) was regulated with subnanometer precision
by the cross-linker length. Ag nanoparticles with an average size of 0.9, 1.3,
and 1.8 nm were produced inside the nanopores thanks to the combined effect of
spatially confined reduction and stabilization of the nanoparticles by the
polymer carboxylic groups. At the same time, strong Ag migration occurred in the
surface region, resulting in the formation of a nanostructured metallic top layer
composed of large (10-20 nm) NPs.
PMID- 28707453
TI - Dignity is a useful concept for bioethics.
PMID- 28707454
TI - Interventions for postoperative pain in children: An overview of systematic
reviews.
AB - The aim of this study was to conduct an overview of systematic reviews that
summarizes the results about efficacy and safety from randomized controlled
trials involving the various strategies used for postoperative pain management in
children. We searched the Cochrane Database of Systematic Reviews, CINAHL,
Database of Reviews of Effect, Embase, MEDLINE, and PsycINFO from the earliest
date to January 24, 2016. This overview included 45 systematic reviews that
evaluated interventions for postoperative pain in children. Out of 45 systematic
reviews that investigated various interventions for postoperative pain in
children, 19 systematic reviews (42%) presented conclusive evidence of efficacy.
Positive conclusive evidence was reported in 18 systematic reviews (40%) for the
efficacy of diclofenac, ketamine, caudal analgesia, dexmedetomidine, music
therapy, corticosteroid, epidural analgesia, paracetamol, and/or nonsteroidal
anti-inflammatory drugs and transversus abdominis plane block. Only one
systematic review reported conclusive evidence of equal efficacy that involved a
comparison of dexmedetomidine vs morphine and fentanyl. Safety of interventions
was reported as conclusive in 14 systematic reviews (31%), with positive
conclusive evidence for dexmedetomidine, corticosteroid, epidural analgesia,
transversus abdominis plane block, and clonidine. Seven systematic reviews
reported equal conclusive safety for epidural infusion, diclofenac intravenous vs
ketamine added to opioid analgesia, bupivacaine, ketamine, paracetamol, and
dexmedetomidine vs intravenous infusions of various opioid analgesics, oral
suspension and suppository of diclofenac, only opioid, normal saline, no
treatment, placebo, and midazolam. Negative conclusive statement for safety was
reported in one systematic review for caudal analgesia vs noncaudal regional
analgesia. More than half of systematic reviews included in this overview were
rated as having medium methodological quality. Of 45 included systematic reviews,
10 were Cochrane reviews and they had higher methodological quality than non
Cochrane reviews. As evidence concerning efficacy and safety is inconclusive for
most of the analyzed interventions, our review points out the need for more
rigorous trials concerning pain management in children.
PMID- 28707455
TI - Human brown adipose tissue as a target for obesity management; beyond cold
induced thermogenesis.
AB - Elevating energy expenditure via adaptive thermogenesis in brown adipose tissue
(BAT) is a potential strategy to reverse obesity. Much early enthusiasm for this
approach, based on rodent studies, was tempered by the belief that BAT was
relatively inconsequential in healthy adult humans. Interest was reinvigorated a
decade ago when a series of studies re-identified BAT, primarily in upper
thoracic regions, in adults. Despite the ensuing explosion of pre-clinical
investigations and identification of an extensive list of potential target
molecules for BAT recruitment, our understanding of human BAT physiology remains
limited, particularly regarding interventions which might hold therapeutic
promise. Cold-induced BAT thermogenesis (CIT) has been well studied, although is
not readily translatable as an anti-obesity approach, whereas little is known
regarding the role of BAT in human diet-induced thermogenesis (DIT). Furthermore,
human studies dedicated to translating known pharmacological mechanisms of
adipose browning from animal models are sparse. Several lines of recent evidence
suggest that molecular regulation and physiology of human BAT differ to that of
laboratory rodents, which form the majority of our knowledge base. This review
will summarize knowledge on CIT and expand upon the current understanding and
evidence gaps related to human adaptive thermogenesis via mechanisms other than
cold.
PMID- 28707456
TI - A novel HLA class II allele, HLA-DQB1*03:73.
AB - The HLA-DQB1*03:73 allele differs from DQB1*03:01:01:01 by 1 nucleotide
substitution at position 209.
PMID- 28707457
TI - Clinical value of integrated-signature miRNAs in esophageal cancer.
AB - MicroRNAs (miRNAs) are crucial regulators of gene expression in tumorigenesis and
are of great interest to researchers, but miRNA profiles are often inconsistent
between studies. The aim of this study was to confirm candidate miRNA biomarkers
for esophageal cancer from integrated-miRNA expression profiling data and TCGA
(The Cancer Genome Atlas) data in tissues. Here, we identify five significant
miRNAs by a comprehensive analysis in esophageal cancer, and two of them (hsa-miR
100-5p and hsa-miR-133b) show better prognoses with significant difference for
both 3-year and 5-year survival. Additionally, they participate in esophageal
cancer occurrence and development according to KEGG and Panther enrichment
analyses. Therefore, these five miRNAs may serve as miRNA biomarkers in
esophageal cancer. Analysis of differential expression for target genes of these
miRNAs may also provide new therapeutic alternatives in esophageal cancer.
PMID- 28707458
TI - Metals and health: facts and myths.
PMID- 28707459
TI - Nationwide Trends in the Incidence of Melanoma and Non-melanoma Skin Cancers from
1999 to 2014 in South Korea.
AB - Purpose: This descriptive study was aimed to examine trends in the incidence of
melanoma and nonmelanoma in South Korea. Materials and Methods: The nationwide
incidence data for melanoma and non-melanoma skin cancer was obtained from the
Korea Central Cancer Registry. Age-standardized rates were calculated and
analyzed, using a Joinpoint regression model. Results: The incidence of basal
cell carcinoma has increased dramatically both in men (average annual percentage
change [AAPC], 8.0 [95% confidence interval (CI), 6.0 to 10.1]) and women (AAPC,
9.0 [95% CI, 7.5 to 10.4]). Squamous cell carcinoma has also steadily increased
both in men (AAPC, 3.3 [95% CI, 2.6 to 4.0]) and women (AAPC, 6.8 [95% CI, 5.3 to
8.4]). Cutaneous melanoma increased continuously from 1999 to 2014 inwomen (AAPC,
3.5 [95% CI, 2.4 to 4.6]), whilst rapidly increasing in men until 2005 (APC, 7.9
[95% CI, 2.4 to 13.7]) after which no increase has been observed (APC, -0.2 [95%
CI, -2.3 to 2.0]). Conclusion: The incidence rates of melanoma and non-melanoma
skin cancer have increased over the past years, with the exception of melanoma in
men. Further studies are required to investigate the reasons for the increased
incidence of these skin cancers in South Korea.
PMID- 28707460
TI - The Effect of Hospice Consultation on Aggressive Treatment of Lung Cancer.
AB - Purpose: The aims of this study were to investigate trends of aggressive
treatment of non-small cell lung cancer (NSCLC) patients at the end-of-life (EOL)
during the recent 5 years and examine the relationship between hospice
consultation (HC) and aggressive care. Materials and Methods: The medical records
of 789 patients with stage IIIB-IV NSCLC at Seoul National University Hospital
(SNUH) who received palliative chemotherapy and died from 2010 to 2014 were
retrospectively reviewed. Indicators of aggressive treatment were evaluated, and
the association of HC with these indicators was analyzed. Results: During the
last 5 years, the frequency of HC increased from 26.7% to 43.6%. The time
interval from last chemotherapy to death increased, and the proportion of
patients who received palliative chemotherapy, visited an emergency room, were
admitted to intensive care unit, during the last month of life, and died in SNUH
significantly decreased over time. Referral to HC was significantly associated
with lower intensive care unit admission rates, lower out-of-hospital death
rates, and less use of the chemotherapy within 1 month prior to death. Overall
survival did not differ by HC. Conclusion: The pattern of cancer care nearthe EOL
has become less aggressivewhen HCwas provided. The positive association of HCwith
better EOL care suggests that providing HC at the optimal time might help to
avoid futile aggressive treatment.
PMID- 28707461
TI - Which Patients with Isolated Para-aortic Lymph Node Metastasis Will Truly Benefit
from Extended Lymph Node Dissection for Colon Cancer?
AB - Purpose: The prognosis of patientswith colon cancer and para-aortic lymph node
metastasis (PALNM) is poor. We analyzed the prognostic factors of extramesenteric
lymphadenectomy for colon cancer patients with isolated PALNM. Materials and
Methods: We retrospectively reviewed 49 patients with PALNM who underwent
curative resection between October 1988 and December 2009. Results: In univariate
analyses, the 5-year overall survival (OS) and disease-free survival (DFS) rates
were higher in patients with <= 7 positive para-aortic lymph node (PALN) (36.5%
and 27.5%) than in those with > 7 PALN (14.3% and 14.3%; p=0.010 and p=0.027,
respectively), and preoperative carcinoembryonic antigen (CEA) level > 5 was also
correlated with a lower 5-year OS and DFS rate of 21.5% and 11.7% compared with
those with CEA <= 5 (46.3% and 41.4%; p=0.122 and 0.039, respectively).
Multivariate analysis found that the number of positive PALN (hazard ratio [HR],
3.291; 95% confidence interval [CI], 1.309 to 8.275; p=0.011) was an independent
prognostic factor for OS and the number of positive PALN (HR, 2.484; 95% CI,
0.993 to 6.211; p=0.052) and preoperative CEA level (HR, 1.953; 95% CI, 0.940 to
4.057; p=0.073) were marginally independent prognostic factors for DFS. According
to our prognostic model, the 5-year OS and DFS rate increased to 59.3% and 53.3%,
respectively, in patients with <= 7 positive PALN and CEA level <= 5. Conclusion:
PALN dissection might be beneficial in carefully selected patients with a low CEA
level and less extensive PALNM.
PMID- 28707463
TI - Meeting of the Global Advisory Committee on Vaccine Safety, 7-8 June 2017.
PMID- 28707462
TI - Pretreatment Serum Amyloid A and C-reactive Protein Comparing with Epstein-Barr
Virus DNA as Prognostic Indicators in Patients with Nasopharyngeal Carcinoma: A
Prospective Study.
AB - Purpose: The measuring Epstein-Barr virus (EBV) DNA is an important predictor of
nasopharyngeal carcinoma (NPC). This study evaluated the predictive value of
pretreatment serum amyloid A (SAA) and C-reactive protein (CRP) comparing with
EBV DNA in patients with NPC. Materials and Methods: In an observational study of
419 non-metastatic NPC patients, we prospectively evaluated the prognostic
effects of pretreatment SAA, CRP, and EBV DNA on survival. The primary endpoint
was progress-free survival (PFS). Results: The median level of SAA and CRP was
4.28 mg/L and 1.88 mg/L, respectively. For the highSAA group (> 4.28 mg/L) versus
the low-SAA (<= 4.28 mg/L) group and the high-CRP group (> 1.88 mg/L) versus the
low-CRP (<= 1.88 mg/L) group, the 5-year PFS was 64.5% versus 73.1% (p=0.013) and
65.2% versus 73.3% (p=0.064), respectively. EBV DNA detection showed a superior
predictive result, the 5-year PFS in the EBV DNA >= 1,500 copies/mL group was
obviously different than the EBV DNA < 1,500 copies/mL group (62.2% versus 77.8%,
p < 0.001). Multifactorial Cox regression analysis confirmed that in the PFS, the
independent prognostic factors were including EBV DNA (hazard ratio [HR], 1.788;
p=0.009), tumour stage (HR, 1.903; p=0.021), and node stage (HR, 1.498; p=0.049),
but the SAA and CRP were not included in the independent prognostic factors.
Conclusion: The results of SAA and CRP had a certain relationship with the
prognosis of NPC, and the prognosis of patients with high level of SAA and CRP
were poor. However, the predictive ability of SAA and CRP was lower than that of
EBV DNA.
PMID- 28707464
TI - Biosynthesis of L-Erythrose by Assembly of Two Key Enzymes in Gluconobacter
oxydans.
AB - L-erythrose, a rare aldotetrose, possesses various pharmacological activities.
However, efficient L-erythrose production is challenging. Currently, L-erythrose
is produced by a two-step fermentation process from erythritol. Here, we describe
a novel strategy for the production of L-erythrose in Gluconobacter oxydans (G.
oxydans) by localizing the assembly of L-ribose isomerase (L-RI) to membrane
bound sorbitol dehydrogenase (SDH) via the protein-peptide interactions of the
PDZ domain and PDZ ligand. To demonstrate this self-assembly, green fluorescent
protein (GFP) replaced L-RI and its movement to membrane-bound SDH was observed
by fluorescence microscopy. The final L-erythrose production was improved to 23.5
g/L with the stepwise metabolic engineering of G. oxydans, which was 1.4-fold
higher than that obtained using coexpression of SDH and L-RI in G. oxydans. This
self-assembly strategy shows remarkable potential for further improvement of L
erythrose production.
PMID- 28707465
TI - Ultrastretchable and Self-Healing Double-Network Hydrogel for 3D Printing and
Strain Sensor.
AB - On the basis of the thermoreversible sol-gel transition behavior of kappa
carrageenan in water, a double-network (DN) hydrogel has been fabricated by
combining an ionically cross-linked kappa-carrageenan network with a covalently
cross-linked polyacrylamide (PAAm) network. The kappa-carrageenan/PAAm DN
hydrogel demonstrated an excellent recoverability and significant self-healing
capability (even when notched). More importantly, the warm pregel solution of
kappa-carrageenan/AAm can be used as an ink of a three-dimensional (3D) printer
to print complex 3D structures with remarkable mechanical strength after UV
exposure. Furthermore, the kappa-carrageenan/PAAm DN hydrogel exhibited a great
strain sensitivity with a gauge factor of 0.63 at the strain of 1000%, and thus,
the hydrogel can be used as sensitive strain sensors for applications in robotics
and human motion detection.
PMID- 28707466
TI - Directional Solvent Vapor Annealing for Crystal Alignment in Solution-Processed
Organic Semiconductors.
AB - A unified approach of directional solvent vapor annealing for crystal alignment
in solution-processed organic semiconductors is proposed. Highly crystalline
molecular self-assembly of the drop-cast technique is further enhanced by
postprocessing scheme of the solvent vapor annealing with additional benefit of
alignment of the crystalline domains. In this technique, a mixture of carrier gas
and solvent vapors are made to flow in a certain direction and in the close
proximity of the surface of the substrates carrying the solution. Flow of the
carrier gas imparts directionality to the semiconducting crystalline ribbons,
whereas the influx of the solvent vapors improves the crystalline order in the
semiconducting film. The flow rate of the carrier gas and the position of the
substrate in the interaction chamber are the primary regulating factors, which
have the ability to provide a semiconducting layer with a well-aligned and
interconnected assembly of long ribbons. These favorable film properties further
materialize in the form of electrical performance of the corresponding field
effect transistors. The versatility of this technique makes it a viable
alternative for the solution processing of organic semiconductors.
PMID- 28707467
TI - Simple Model of the Effect of Solution Conditions on the Nucleation of Amyloid
Fibrils.
AB - It is well known that peptide and protein fibrillation is strongly affected by
the solution conditions, but a fundamental understanding of how amyloid fibril
nucleation depends on solution pH, salt concentration, and solvent is absent.
Here, we use expressions from Debye-Huckel theory to describe the interactions
between charged amino acids in combination with our recently developed
nonstandard nucleation theory to predict the concentration dependence of the
fibril nucleation rate under different solvent conditions. The general rule that
emerges from these considerations is that changes in solution pH, salt
concentration, and solvent that increase the bonding energy between the fibril
building blocks decrease the fibril solubility and promote fibril nucleation, in
line with experimental observations. The simple analytical relations among the
nucleation rate, fibril solubility, and binding energies provide a tool to
controlling and understanding amyloid fibril formation by changing the solution
conditions.
PMID- 28707468
TI - Prediction of Novel High-Pressure Structures of Magnesium Niobium Dihydride.
AB - On the basis of a combination of the particle-swarm optimization technique and
density functional theory (DFT), we explore the crystal structures of MgH2, NbH2,
and MgNbH2 under high pressure. The enthalpy-pressure (H-P) diagrams indicate
that the structural transition sequence of MgH2 is alpha -> gamma -> delta ->
epsilon -> zeta and that NbH2 transforms from the Fm3m phase to the Pnma phase at
47.80 GPa. However, MgNbH2 is unstable when the pressure is too low or too high.
Two novel MgNbH2 structures, the hexagonal P6m2 phase and the orthorhombic Cmcm
phase, are discovered, which are stable in the pressure ranges of 13.24-128.27
GPa and 128.27-186.77 GPa, respectively. The P6m2 phase of MgNbH2 consists of
alternate layers of polymetric NbH6 and MgH6 triangular prisms, while the Cmcm
phase contains distorted MgH6 trigonal prisms. The calculated elastic constants
and phonon dispersions confirm that both phases are mechanically and dynamically
stable. The analyses of density of states (DOS), electron localization function
(ELF), and Bader charge demonstrate that a combination of ionic and metallic
bonds exist in both P6m2 and Cmcm phases. We hope the newly predicted magnesium
niobium dihydrides with desirable electronic properties will promote future
experimental and theoretical studies on mixed main group-transition metal
hydrides.
PMID- 28707469
TI - Oxygen Vacancy Linear Clustering in a Perovskite Oxide.
AB - Oxygen vacancies have been implicitly assumed isolated ones, and understanding
oxide materials possibly containing oxygen vacancies remains elusive within the
scheme of the isolated vacancies, although the oxygen vacancies have been playing
a decisive role in oxide materials. Here, we report the presence of oxygen
vacancy linear clusters and their orientation along a specific crystallographic
direction in SrTiO3, a representative of a perovskite oxide. The presence of the
linear clusters and associated electron localization was revealed by an
electronic structure represented in the increase in the Ti2+ valence state or
corresponding Ti 3d2 electronic configuration along with divacancy cluster model
analysis and transport measurement. The orientation of the linear clusters along
the [001] direction in perovskite SrTiO3 was verified by further X-ray diffuse
scattering analysis. Because SrTiO3 is an archetypical perovskite oxide, the
vacancy linear clustering with the specific aligned direction and electron
localization can be extended to a wide variety of the perovskite oxides.
PMID- 28707470
TI - Enhancement of Naringenin Biosynthesis from Tyrosine by Metabolic Engineering of
Saccharomyces cerevisiae.
AB - Flavonoids are an important class of plant polyphenols that possess a variety of
health benefits. In this work, S. cerevisiae was metabolically engineered to
produce the flavonoid naringenin, using tyrosine as the precursor. Our strategy
to improve naringenin production comprised three modules. In module 1, we
employed a modified GAL system to overexpress the genes of the naringenin
biosynthesis pathway and investigated their synergistic action. In module 2, we
simultaneously up-regulated acetyl-CoA production and down-regulated fatty acid
biosynthesis in order to increase the precursor supply, malonyl-CoA. In module 3,
we engineered the tyrosine biosynthetic pathway to eliminate the feedback
inhibition of tyrosine and also down-regulated competing pathways. It was found
that modules 1 and 3 played important roles in improving naringenin production.
We succeeded in producing up to ~90 mg/L of naringenin in our final strain, which
is a 20-fold increase as compared to the parental strain.
PMID- 28707471
TI - One-Step Identification of Antibody Degradation Pathways Using Fluorescence
Signatures Generated by Cross-Reactive DNA-Based Arrays.
AB - Therapeutic antibodies are prone to degradation via a variety of pathways during
each stage of the manufacturing process. Hence, a low-cost, rapid, and broadly
applicable tool that is able to identify when and how antibodies degrade would be
highly desirable to control the quality of therapeutic antibody products. With
this goal in mind, we have developed signature-based sensing system to
discriminate differently degraded therapeutic antibodies. The use of arrays
consisting of conjugates between nanographene oxide and fluorophore-modified
single-stranded DNAs under acidic pH conditions generated unique fluorescence
signatures for each state of the antibodies. Multivariate analyses of the thus
obtained signatures allowed identifying (i) common features of native, denatured,
and visibly aggregated antibodies, (ii) complicated degradation pathways of
therapeutic omalizumab upon time-course heat-treatment, and (iii) the individual
compositions of differently degraded omalizumab mixtures. As the signature-based
sensing has the potential to identify a broad range of degraded antibodies formed
by different kinds of realistic stress types, this system may serve as the basis
for high-throughput assays for the screening of antibody manufacturing processes.
PMID- 28707472
TI - One-Transistor-One-Transistor (1T1T) Optoelectronic Nonvolatile MoS2 Memory Cell
with Nondestructive Read-Out.
AB - Taking advantage of the superlative optoelectronic properties of single-layer
MoS2, we developed a one-transistor-one-transistor (1T1T)-type MoS2
optoelectronic nonvolatile memory cell. The 1T1T memory cell consisted of a
control transistor (CT) and a memory transistor (MT), in which the drain
electrode of the MT was connected electrically to the gate electrode of the CT,
whereas the source electrode of the CT was connected electrically to the gate
electrode of the MT. Single-layer MoS2 films were utilized as the channel
materials in both transistors, and gold nanoparticles acted as the floating gates
in the MT. This 1T1T device architecture allowed for a nondestructive read-out
operation in the memory because the writing (programming or erasing) and read-out
processes were operated separately. The switching of the CT could be controlled
by light illumination as well as the applied gate voltage due to the strong light
absorption induced by the direct band gap of single-layer MoS2 (~1.8 eV). The
resulting MoS2 1T1T memory cell exhibited excellent memory performance, including
a large programming/erasing current ratio (over 106), multilevel data storage
(over 6 levels), cyclic endurance (200 cycles), and stable retention (103 s).
PMID- 28707473
TI - Aggregatibacter actinomycetemcomitans Growth in Biofilm versus Planktonic State:
Differential Expression of Proteins.
AB - Aggregatibacter actinomycetemcomitans (Aa) is a pathogenic bacterium residing in
the subgingival plaque biofilm strongly associated with the pathogenesis of
periodontitis. The aim of this investigation was to study the protein
differential expression of Aa when growing on biofilm compared with planktonic
state using proteomic analysis by the 2D-DIGE system. Eighty-seven proteins were
differentially expressed during biofilm growth (1.5-fold, p < 0.05), with 13
overexpressed and 37 down-expressed. Those repressed were mainly proteins
involved in metabolism, biosynthesis, and transport. The overexpressed proteins
were outer membrane proteins (OMPs) and highly immunogenic proteins such as YaeT
(OMP), FtsZ, OMP39, OMP18/16, the chaperone GroEL, OMPA, adenylate kinase (Adk),
and dihydrolipoamide acetyltransferase. The enrichment fractions of the OMPs from
biofilm and planktonic states were obtained, and these proteins were analyzed by
Western blotting with human serum from a periodontitis patient and one healthy
control. These immunogenic proteins overexpressed in the biofilm may represent
candidate virulence factors.
PMID- 28707474
TI - Native Hydrophobic Binding Interactions at the Transition State for Association
between the TAZ1 Domain of CBP and the Disordered TAD-STAT2 Are Not a
Requirement.
AB - A significant fraction of the eukaryotic proteome consists of proteins that are
either partially or completely disordered under native-like conditions.
Intrinsically disordered proteins (IDPs) are common in protein-protein
interactions and are involved in numerous cellular processes. Although many
proteins have been identified as disordered, much less is known about the binding
mechanisms of the coupled binding and folding reactions involving IDPs. Here we
have analyzed the rate-limiting transition state for binding between the TAZ1
domain of CREB binding protein and the intrinsically disordered transactivation
domain of STAT2 (TAD-STAT2) by site-directed mutagenesis and kinetic experiments
(Phi-value analysis) and found that the native protein-protein binding interface
is not formed at the transition state for binding. Instead, native hydrophobic
binding interactions form late, after the rate-limiting barrier has been crossed.
The association rate constant in the absence of electrostatic enhancement was
determined to be rather high. This is consistent with the Phi-value analysis,
which showed that there are few or no obligatory native contacts. Also, linear
free energy relationships clearly demonstrate that native interactions are
cooperatively formed, a scenario that has usually been observed for proteins that
fold according to the so-called nucleation-condensation mechanism. Thus, native
hydrophobic binding interactions at the rate-limiting transition state for
association between TAD-STAT2 and TAZ1 are not a requirement, which is generally
in agreement with previous findings on other IDP systems and might be a common
mechanism for IDPs.
PMID- 28707475
TI - Exit Outcomes for Probation-Supervised Youth in Foster Care: An Examination of
Past Child Protection Involvement.
AB - Research on youth in foster care has focused on those placed for reasons of
maltreatment rather than delinquency, yet most states provide foster care
services to youth under probation supervision. This analysis generated knowledge
about youth in probation-supervised foster care (PSFC) in California by examining
the relationship between past child protective services (CPS) involvement and
exit type. CPS records were extracted to identify 17-year-old youths in PSFC
between 2008 and 2012 ( N = 11,188). The relationship between allegations of
maltreatment and exit type was assessed using regression models. Of the PSFC
youth, 64.6% had previous allegations of maltreatment and a quarter had been
reported at least 6 times. Youth with a history of placement in CPS foster care
were more likely to age out relative to achieving permanency in comparison to
PSFC youth with no maltreatment history (relative risk ratio = 2.20; 95%
confidence interval [1.90, 2.55]). As the number of reports increased, the
likelihood of exiting care by aging out increased relative to achieving
permanency ( p < .001). The findings suggest a majority of PSFC youth had
maltreatment histories, the overlap between CPS and probation was constant, and
maltreatment records may characterize youth in PSFC at risk of negative exits
from care.
PMID- 28707476
TI - Clinical research and the medical research future fund.
PMID- 28707477
TI - Response to the best available treatment for bulimia nervosa and binge-eating
disorder is disease severity-dependent.
PMID- 28707478
TI - Emotional contagion in the consultation-liaison setting.
PMID- 28707479
TI - Axitinib in metastatic renal cell carcinoma: beyond the second-line setting.
AB - Treatment options for advanced and metastatic renal cell carcinoma have advanced
considerably in the past decade with the approval of several targeted agents,
including axitinib. Axitinib is a potent and selective inhibitor of VEGFRs 1-3,
and is well established as second-line treatment. This article summarizes factors
to be considered when administering axitinib, such as individualized dose
titration and axitinib-associated adverse events, in order to retain patients
longer on treatment, which would likely lead to improved efficacy outcomes. In
addition, potential clinical perspectives for axitinib beyond the second-line
setting, including its role in the first-line setting, sequential therapy,
neoadjuvant and adjuvant therapies, and combination therapy with immunotherapy,
in particular, immune checkpoint inhibitors, are discussed.
PMID- 28707480
TI - In ovo silver nanoparticle supplementation for improving the post-hatch immunity
status of broiler chickens.
AB - Silver nanoparticles (AgNano) are known for their unique physical, chemical and
biological properties, enabling cell penetration and anti-inflammatory response.
In Experiment 1, the effect of an in ovo administration of AgNano (15 ug/egg; n =
360) at different incubation times (d 7 and d 18) on hatchability parameters was
explored. In Experiment 2, post-hatch performance of broilers (42 d, n = 250) was
studied after in ovo AgNano administration: Group T1 remained un-injected, Group
T2 was the sham control and Groups T3, T4 and T5 were injected with 12.5, 25 and
50 ug AgNano, respectively, at 18 d of incubation. Chick weight, chick to egg
weight ratio and hatchability as well average daily gain, average daily feed
intake and feed conversion ratio were similar in all treatment groups. No
variation was seen in the weight of thymus; however, the bursa and spleen weight
was increased (p < 0.05) in Groups T4 and T5 in comparison to Group T1. The in
vivo immune response to phytohaemagglutinin-P was increased in Group T3 in
comparison to Groups T1 and T2 (p < 0.05), while the response to sheep red blood
cells was increased in all AgNano-treated groups in comparison with Group T1 (p <
0.01). The expression of toll-like receptors 2 and 4 genes was up-regulated in
AgNano groups in comparison with Groups T1 and T2 (p < 0.01). In summary, an in
ovo supplementation of AgNano carried out at d 18 of incubation is effective and
modulates the post-hatch immune response without affecting the hatchability,
growth and other performance parameters in broilers.
PMID- 28707481
TI - Protective effects of melatonin and memantine in human retinal pigment epithelium
(ARPE-19) cells against 2-ethylpyridine-induced oxidative stress: implications
for age-related macular degeneration.
AB - PURPOSE: To investigate the possible protective effects of melatonin and
memantine (MMT) against 2-ethylpyridine (2-EP)-induced oxidative stress and
mitochondrial dysfunction in human RPE (ARPE-19) cells in vitro. MATERIALS AND
METHODS: The ARPE-19 cells were divided into seven groups. Oxidative stress was
triggered by incubating the ARPE-19 cells with 30 MUM of 2-EP for 24 h. Then, 200
MUM of melatonin was administered over three days and 20 MUM of MMT over six
hours prior to the experiment. The effects of melatonin and MMT on the
intracellular calcium release mechanism, reactive oxygen species production,
caspase-3 and caspase-9 activities, as well as vascular endothelial growth factor
levels were measured. RESULTS: Melatonin and MMT were found to significantly
decrease apoptosis levels. The intracellular calcium release was regulated by
both melatonin and MMT. Further, melatonin and MMT significantly decreased both
caspase-3 and caspase-9 activities, as well as pro-caspase and poly(ADP-ribose)
polymerase expression, in ARPE-19 cells. Moreover, melatonin significantly
increased the protective effect of MMT. The combination of melatonin and MMT
significantly decreased 2-EP-induced oxidative toxicity and apoptosis by
inhibiting the intracellular reactive oxygen species production and mitochondrial
depolarization levels. CONCLUSIONS: These notable findings are the first to
demonstrate the synergistic protective effects of melatonin and MMT against 2-EP
induced oxidative stress in ARPE-19 cells.
PMID- 28707483
TI - Investigational drugs in development for focal segmental glomerulosclerosis.
AB - INTRODUCTION: Focal segmental glomerulosclerosis is an important cause of end
stage kidney disease and is a paradigm for the study of glomerular scarring.
There are no FDA approved treatments for this condition. Current therapies,
assessed based on reduction in proteinuria, are generally effective in a subset
of patients which suggests that FSGS is a heterogeneous group of glomerular
disorders or podocytopathies that converge on a common histopathological
phenotype. Areas covered: We searched for investigational drugs agents that
target different pathophysiological pathways using the key words 'FSGS' and
'podocyte' in American and European clinical trial registers (clinicaltrials.gov;
clinicaltrialsregister.eu). Published articles were searched in PubMed, Medline,
the Web of Science and the Cochrane Central Register of Controlled Trials
Library. Expert opinion: Progress is being made in defining the mechanism of
action of subtypes of FSGS. Current and investigational therapies for FSGS target
these different pathways of injury. It is anticipated that advances in systems
biology will further refine the classification of FSGS by subdividing the disease
based on the primary mechanism of glomerular injury, identify biomarkers to
discriminate between different subtypes, and enable appropriate selection of
appropriate therapy for each individual in accordance with the goals of precision
medicine.
PMID- 28707482
TI - Peripheral Inflammation, Apolipoprotein E4, and Amyloid-beta Interact to Induce
Cognitive and Cerebrovascular Dysfunction.
AB - Cerebrovascular dysfunction is rapidly reemerging as a major process of
Alzheimer's disease (AD). It is, therefore, crucial to delineate the roles of AD
risk factors in cerebrovascular dysfunction. While apolipoprotein E4 ( APOE4),
Amyloid-beta (Abeta), and peripheral inflammation independently induce
cerebrovascular damage, their collective effects remain to be elucidated. The
goal of this study was to determine the interactive effect of APOE4, Abeta, and
chronic repeated peripheral inflammation on cerebrovascular and cognitive
dysfunction in vivo. EFAD mice are a well-characterized mouse model that express
human APOE3 (E3FAD) or APOE4 (E4FAD) and overproduce human Abeta42 via expression
of 5 Familial Alzheimer's disease (5xFAD) mutations. Here, we utilized EFAD
carriers [5xFAD+/-/ APOE+/+ (EFAD+)] and noncarriers [5xFAD-/-/ APOE+/+ (EFAD-)]
to compare the effects of peripheral inflammation in the presence or absence of
human Abeta overproduction. Low-level, chronic repeated peripheral inflammation
was induced in EFAD mice via systemic administration of lipopolysaccharide (LPS;
0.5 mg/kg/wk i.p.) from 4 to 6 months of age. In E4FAD+ mice, peripheral
inflammation caused cognitive deficits and lowered post-synaptic protein levels.
Importantly, cerebrovascular deficits were observed in LPS-challenged E4FAD+
mice, including cerebrovascular leakiness, lower vessel coverage, and cerebral
amyloid angiopathy-like Abeta deposition. Thus, APOE4, Abeta, and peripheral
inflammation interact to induce cerebrovascular damage and cognitive deficits.
PMID- 28707484
TI - Autoregressive Modeling of Drift and Random Error to Characterize a Continuous
Intravascular Glucose Monitoring Sensor.
AB - BACKGROUND: Continuous glucose monitoring (CGM) devices have been effective in
managing diabetes and offer potential benefits for use in the intensive care unit
(ICU). Use of CGM devices in the ICU has been limited, primarily due to the
higher point accuracy errors over currently used traditional intermittent blood
glucose (BG) measures. General models of CGM errors, including drift and random
errors, are lacking, but would enable better design of protocols to utilize these
devices. This article presents an autoregressive (AR) based modeling method that
separately characterizes the drift and random noise of the GlySure CGM sensor
(GlySure Limited, Oxfordshire, UK). METHODS: Clinical sensor data (n = 33) and
reference measurements were used to generate 2 AR models to describe sensor drift
and noise. These models were used to generate 100 Monte Carlo simulations based
on reference blood glucose measurements. These were then compared to the original
CGM clinical data using mean absolute relative difference (MARD) and a Trend
Compass. RESULTS: The point accuracy MARD was very similar between simulated and
clinical data (9.6% vs 9.9%). A Trend Compass was used to assess trend accuracy,
and found simulated and clinical sensor profiles were similar (simulated trend
index 11.4 degrees vs clinical trend index 10.9 degrees ). CONCLUSION: The model
and method accurately represents cohort sensor behavior over patients, providing
a general modeling approach to any such sensor by separately characterizing each
type of error that can arise in the data. Overall, it enables better protocol
design based on accurate expected CGM sensor behavior, as well as enabling the
analysis of what level of each type of sensor error would be necessary to obtain
desired glycemic control safety and performance with a given protocol.
PMID- 28707485
TI - Common and uncommon adverse cutaneous reactions to erlotinib: a study of 20
Chinese patients with cancer.
AB - OBJECTIVE: This study presented common lesions with systemic toxicities and
uncommon adverse cutaneous reactions such as anaphylactic dermatitis in patients
undergoing treatment with erlotinib for the benefit of practicing dermatologists
and oncologists. METHODS: Adverse cutaneous reactions associated with erlotinib
were reported in 20 Chinese patients with cancer. RESULTS: Adverse cutaneous
reactions reported included six cases of anaphylactic dermatitis, 12 cases of
acneiform rash, nine cases of xerosis, five cases of nail changes and four cases
of hair changes. One case of anaphylactic dermatitis manifested as erythema with
swelling on the face and neck, and others as erosive and scaly erythema on the
fold of skin, or red macules, papules, plaques and pigmentation on the whole
body. Clinical details indicated anaphylactic reactions, including a high
percentage of eosinophils in the peripheral blood, eosinophilic infiltration in
the dermis layer and good response to antihistamines and topical steroids.
Systemic toxicities accompanied by cutaneous reactions occurred in five patients
including one case of anaphylactic dermatitis and four cases of acneiform rash.
Elevated hepatic enzymes were observed among all the patients with grade-3 or
grade-4 acneiform rashes. One patient with anaphylactic dermatitis and one with
acneiform rash discontinued erlotinib administration due to severe lesions, high
fever or severe elevation of hepatic enzymes. CONCLUSIONS: Anaphylactic cutaneous
reactions caused by erlotinib are rarely described hitherto. Systemic toxicities
should be emphasized especially in cases with severe skin disorders. Timely
detection and appropriate early intervention in patients who develop severe
cutaneous reaction while on erlotinib therapy should be considered clinically.
PMID- 28707486
TI - Working towards dengue as a vaccine-preventable disease: challenges and
opportunities.
AB - INTRODUCTION: Dengue is an emerging viral disease that affects the human
population around the globe. Recent advancements in dengue virus research have
opened new avenues for the development of vaccines against dengue. The
development of a vaccine against dengue is a challenging task because any of the
four serotypes of dengue viruses can cause disease. The development of a dengue
vaccine aims to provide balanced protection against all the serotypes. Several
dengue vaccine candidates are in the developmental stages such as inactivated,
live attenuated, recombinant subunit, and plasmid DNA vaccines. Area covered: The
authors provide an overview of the progress made in the development of much
needed dengue vaccines. The authors include their expert opinion and their
perspectives for future developments. Expert opinion: Human trials of a live
attenuated tetravalent chimeric vaccine have clearly demonstrated its potential
as a dengue vaccine. Other vaccine candidate molecules such as DENVax, a
recombinant chimeric vaccine andTetraVax, are at different stages of development
at this time. The authors believe that the novel strategies for testing and
improving the immune response of vaccine candidates in humans will eventually
lead to the development of a successful dengue vaccine in future.
PMID- 28707487
TI - The role of genetic analysis for predicting outcome of rheumatoid arthritis.
AB - INTRODUCTION: Rheumatoid Arthritis (RA) varies from a mild to a severe,
unremitting illness characterized by uncontrolled inflammation with consequent
damage to cartilage and bone of joints. Individualized therapeutic approaches
based on likely outcome would facilitate a personalized therapeutic approach.
Areas covered: Genetics is known to contribute a significant component of the
variability in RA outcome, estimated at 45-60%. A number of candidate gene
studies have been associated with variability in radiologically assessed joint
damage; however a more comprehensive genome wide analysis is required to more
fully characterize the genetic basis of RA severity. Expert commentary: Genetic
profiling of patient presenting with RA has the potential to aid stratification
based on predicted prognosis, this would inform the clinical development of a
personalized therapeutic approach. It will also result in the identification of
novel mediators of tissue damage in RA.
PMID- 28707488
TI - Efficacy of oxytocin versus carbetocin in prevention of postpartum hemorrhage
after cesarean section under general anesthesia: a prospective randomized
clinical trial.
AB - OBJECTIVE: To compare the use of carbetocin and oxytocin in the prevention of
postpartum hemorrhage after cesarean section. METHODS: The present study was a
prospective double-blind randomized controlled clinical trial performed in two
university-based hospitals in Tehran, Iran. Two hundred and twenty women with the
gestational age of more than 37 weeks, who needed cesarean operation,
participated in the study. Patients were assigned to receive either a single 100
MUg IV dose of carbetocin or a standard 30-international unit IV infusion of
oxytocin during 2 h after delivery of placenta. The primary outcome measures were
postpartum hemorrhage requiring additional uterotonic drugs, bleeding volume, and
the hemoglobin drops. RESULTS: There were meaningful differences in carbetocin
versus oxytocin group regarding the hemoglobin drops (1.01 versus 2.05, p = .01),
bleeding volume (430.68 CC versus 552.6 CC, p < .001), uterine massages frequency
(3.7 versus 4.26, p < .001), and uterine height at 2, 4, and 24 h (p < .001).
Oxytocin side effects were significantly higher in comparison with the carbetocin
except pruritus which was observed in 27% of patients in the carbetocin versus no
cases in the oxytocin group. CONCLUSIONS: It may be concluded that carbetocin is
a good alternative modality to conventional uterotonic agents such as oxytocin
for the prevention of postpartum hemorrhage after cesarean sections. Registration
ID in IRCT: NCT02079558.
PMID- 28707489
TI - Evaluation of microRNA responses in ARPE-19 cells against the oxidative stress.
AB - PURPOSE: This study aimed to determine microRNA (miRNA) expression profile of
human retinal pigment epithelium cell (ARPE-19) against the oxidative stress
induced by hydrogen peroxide (H2O2). METHODS: ARPE-19 cells were incubated with
different concentrations of H2O2 (200, 600 and 800 MUM) for 18 h, and then cell
viability, vascular endothelial growth factor levels and total oxidant status
were evaluated. Expressions of 1152 miRNA were determined by quantitative real
time PCR in each group. RESULTS: Expressions of 90 miRNA were significantly
changed in the ARPE-19 cells incubated with H2O2 compared to control group.
However, miR-143-3p was only found to be expressed in groups incubated with H2O2.
While 24 miRNA (hsa-miR-200c-3p, miR-192-5p, miR-194-5p, miR-141-3p, miR-658, miR
18 b-5p, miR-486-5p, miR-525-3p, miR-493-3p, miR-518d-3p, miR-29 b-1-5p, miR-675
3p, miR-1238-3p, miR-195-3p, miR-1539, miR-490-5p, miR-3200-5p, miR-1273d, miR
130a-5p, miR-30 b-5p, miR-1247-5p, miR-1910-5p, miR27a-5p and miR-200 b-3p)
upregulated due to the increased dose of H2O2, nine miRNA (hsa-miR-96-5p, miR-33a
5p, miR-345-5p, miR-106 b-3p, miR-1285-3p, miR-23 b-5p, miR-27 b-5p, miR-103a-3p
and miR-4289) were also found to be downregulated. CONCLUSION: This study
suggests that oxidative stress may be an important factor on expression of miRNAs
in ARPE-19 cells. These miRNAs may have a role in the pathogenesis of age-related
macular degeneration related to oxidative stress. However, this relationship
needs to be examined in new studies by evaluation of pathways and target genes.
PMID- 28707490
TI - TransferonTM, a peptide mixture with immunomodulatory properties is not
immunogenic when administered with various adjuvants.
AB - Transferon, a human dialyzable leukocyte extract (hDLE), is a biotherapeutic that
comprises a complex mixture of low-molecular-weight peptides (< 10 kDa) and is
used to treat diseases with an inflammatory component. Some biotherapeutics,
including those composed of peptides, can induce anti-drug antibodies (ADA) that
block or diminish their therapeutic effect. Nevertheless, few studies have
evaluated peptide-derived drug immunogenicity. In this study, the immunogenicity
of Transferon was examined in a murine model during an immunization scheme using
the following adjuvants: Al(OH)3, incomplete Freund's adjuvant (IFA), or Titermax
Gold. The inoculation scheme entailed three routes of administration
(intraperitoneal, Day 1; subcutaneous, Day 7; and intramuscular, Day 14) using
200 MUg Transferon/inoculation. Serum samples were collected on Day 21. Total IgG
levels were quantitated by affinity chromatography, and specific antibodies
against components of Transferon were analyzed by dot-blot and ELISA. Ovalbumin
(OVA, 44 kDa) and peptides from hydrolyzed collagen (PFHC, < 17 kDa) were used as
positive and negative controls, respectively, in the same inoculation scheme and
analyses for Transferon. OVA, PFHC, and Transferon increased total IgG
concentrations in mice. However, only IgG antibodies against OVA were detected.
Based on the results, it is concluded that Transferon does not induce generation
of specific antibodies against its components in this model, regardless of
adjuvant and route of administration. These results support the safety of
Transferon by confirming its inability to induce ADA in this animal model.
PMID- 28707491
TI - The effect of omega 3 fatty acid supplementation on premenstrual syndrome and
health-related quality of life: a randomized clinical trial.
AB - INTRODUCTION: Most reproductive aged women suffer from somatic and mental
disorders prior to menstruation. This study investigated whether omega-3
supplement improved premenstrual symptoms and health-related quality of life
among reproductive aged women. METHODS: A multi-center, balanced (1:1), placebo
controlled, parallel-group randomized clinical trial was conducted in an urban
academic institution. A sample consisting of 95 Iranian women aged 20-35 years
who were suffering from premenstrual symptoms were randomly allocated into two
groups. The treatment consisted of omega-3 supplement containing 1 g fish oil.
Placebo was free of oil. The premenstrual symptoms' screening tool and 12-item
short form health survey questionnaire were used for data collection. RESULTS: No
statistically significant differences in the baseline characteristics of the
groups were reported. Most premenstrual symptoms and their interference with
daily activities were significantly reduced over the follow-up period. The mean
score of overeating in the omega-3 supplement group and insomnia in the placebo
group showed no difference between the groups. The longer use of omega-3
supplement provides improvement of premenstrual symptoms and activities. The mean
scores of physical and mental components of quality of life were significantly
improved in the omega-3 supplement and placebo groups. DISCUSSION: The treatment
of premenstrual symptoms using omega-3 supplement reduced symptoms and
ameliorated women's quality of life.
PMID- 28707492
TI - Bisphenol A (BPA) aggravates multiple low-dose streptozotocin-induced Type 1
diabetes in C57BL/6 mice.
AB - Type 1 diabetes (T1D) is a T-cell-mediated autoimmune disorder characterized by
destruction of insulin-producing pancreatic beta-cells. Whereas epidemiological
data implicate environmental factors in the increasing incidence of T1D, their
identity remains unknown. Though exposure to bisphenol A (BPA) has been
associated with several disorders, no epidemiologic evidence has linked BPA
exposure and T1D. The goal of this study was to elucidate diabetogenic potentials
of BPA and underlying mechanisms in the context of T-cell immunity, in a multiple
low-dose streptozotocin (MLDSTZ)-induced autoimmune mouse T1D model. C57BL/6 mice
were orally exposed to 1 or 10 mg BPA/L starting at 4 wk of age; diabetes was
induced at 9 wk of age with STZ. T-cell composition, function, and insulitis
levels were studied at Days 11 and 50 during diabetes development (i.e. post
first STZ injection). Results showed both BPA doses increased diabetes incidence
and affected T-cell immunity. However, mechanisms of diabetogenic action appeared
divergent based on dose. Low-dose BPA fits a profile of an agent that exhibits
pro-diabetogenic effects via T-cell immunomodulation in the early stages of
disease development, i.e. decreases in splenic T-cell subpopulations [especially
CD4+ T-cells] along with a trend in elevation of splenic T-cell formation of pro
inflammatory cytokines (IFN-gamma, TNF-alpha, and IL-6). In contrast, high-dose
BPA did not affect T-cell populations and led to decreased levels of IFN-gamma
and TNF-alpha. Both treatments did not affect insulitis levels at the disease
early stage, but aggravated it later on. By the study end, besides decreasing T
cell proliferative capacity, low-dose BPA did not affect other T-cell-related
parameters, including cytokine secretion, comparable to the effects of high-dose
BPA. In conclusion, this study confirmed BPA as a potential diabetogenic compound
with immunomodulatory mechanisms of action - in the context of T-cell immunity -
that seemed to be dose dependent in the early immunopathogenesis of a MLDSTZ
induced model of T1D.
PMID- 28707493
TI - AB-CHMINACA-induced sudden death from non-cardiogenic pulmonary edema.
AB - CONTEXT: Despite widespread use of diverse synthetic cannabinoid (sCB) compounds,
the pathophysiology associated with intoxication with many sCB compounds,
including AB-CHMINACA, is poorly understood, as is their metabolism and
distribution into blood and organs. CASE DETAILS: A young man died shortly after
ingesting an herb product containing sCB compounds. Toxicological analyses of
blood samples revealed high levels of AB-CHMINACA (7.61 +/- 0.59 ng/mL) and its
metabolites (M2, 56.73 +/- 4.16 ng/mL; M4, 2.29 +/- 0.14 ng/mL) and trace amounts
of 5-fluoro-AMB, FUB-PB-22, and AB-FUBINACA. The autopsy revealed severe
pulmonary edema, and histology showed air bubbles in the alveolar effusion,
suggesting rapid progression of edema. Low blood levels of N-terminal pro-brain
natriuretic peptide excluded cardiogenic pulmonary edema. Histological
examination revealed diffuse neuronal (brain) and myocardial (sub-endocardial)
hyper-eosinophilia, indicating hypoxic encephalopathy and systemic hypoxemia,
respectively. CONCLUSIONS: The findings show that AB-CHMINACA induced rapid
progression of pulmonary edema resulting in hypoxic encephalopathy and systemic
hypoxemia, possibly through severe seizures. The high blood ratio of the M2
metabolite to the parent compound, AB-CHMINACA, demonstrates rapid metabolism.
This highlights the usefulness of quantification of M2 in diagnosing AB-CHMINACA
intoxication.
PMID- 28707494
TI - Dry coating of solid dosage forms: an overview of processes and applications.
AB - Dry coating techniques enable manufacturing of coated solid dosage forms with no,
or very limited, use of solvents. As a result, major drawbacks associated with
both organic solvents and aqueous coating systems can be overcome, such as
toxicological, environmental, and safety-related issues on the one hand as well
as costly drying phases and impaired product stability on the other. The
considerable advantages related to solventless coating has been prompting a
strong research interest in this field of pharmaceutics. In the article,
processes and applications relevant to techniques intended for dry coating are
analyzed and reviewed. Based on the physical state of the coat-forming agents,
liquid- and solid-based techniques are distinguished. The former include hot-melt
coating and coating by photocuring, while the latter encompass press coating and
powder coating. Moreover, solventless techniques, such as injection molding and
three-dimensional printing by fused deposition modeling, which are not purposely
conceived for coating, are also discussed in that they would open new
perspectives in the manufacturing of coated-like dosage forms.
PMID- 28707495
TI - Individualizing the selection of long-acting bronchodilator therapy for patients
with COPD: considerations in primary care.
AB - Chronic obstructive pulmonary disease (COPD) is a common condition encountered in
primary care settings. COPD remains the third leading cause of death in the
United States and carries a significant burden to both patients and the
healthcare system. COPD is a chronic, progressive, irreversible lung disease
associated with high morbidity and mortality. Proper assessment and diagnosis
requires spirometry which is currently underutilized in primary care. Management
is focused on adequate symptom control, improving quality of breathing and
quality of life, and preventing exacerbations and hospitalizations. However, many
patients are not receiving long-acting bronchodilator maintenance therapy as
recommended in current clinical guidelines. Even when patients receive
appropriate therapy, real-world issues such as a patient's health literacy,
physical and cognitive limitations, and therapy nonadherence limit the
effectiveness of prescribed inhaled medications. Primary care providers are well
situated to ensure that prescribed therapies and long-term management goals are
matched to the individual needs of patients with COPD.
PMID- 28707496
TI - Invited Commentary on "Investigating the Reliability and Factor Structure of
Kalichman's 'Survey 2: Research Misconduct' Questionnaire".
PMID- 28707497
TI - Complications of central lines in neonates admitted to a level III Neonatal
Intensive Care Unit.
AB - OBJECTIVE: To investigate the incidence and risk factors for central line related
complications in neonates. METHODS: A retrospective cohort study of infants who
underwent central line (CL) placement, from 1 July 2014 to 31 June 2016, was
conducted in Neonatal Intensive Care Unit of Centro Hospitalar de Sao Joao.
Infants hospitalized more than 2 d and CLs placed for more than 24 h were
included. Patients' demographic characteristics, hospital data, and information
on CLs were collected. Indwelling complications were compared between infant
groups and types of CL inserted. RESULTS: A total of 400 CLs were inserted in 240
infants with a CL utilization ratio of 0.64. Overall CL complication rate was
29.6 per 1000 catheter days. Of all complications, central line-associated
bloodstream infection had the highest incidence (12.4 per 1000 catheter days).
Infiltration was the most reported mechanical complication. Non-umbilical
catheters showed a significantly higher incidence of complications than umbilical
ones. Low gestational age, low birth weight, prolonged catheter stay, long
duration of total parenteral nutrition, and peripherally inserted central
catheter placement were associated with a higher risk of indwelling complication.
CONCLUSIONS: The implementation of measures to prevent catheter-related
complications must be a priority in care of vulnerable neonates.
PMID- 28707498
TI - Epidemiology of injuries in men's lacrosse: injury prevention implications for
competition level, type of play, and player position.
AB - OBJECTIVE: The growth in participation in men's lacrosse has increased the
likelihood of sport-specific injuries, yet there continues to be a need for
specific epidemiological data concerning lacrosse injuries. The purpose of this
literature review is to aggregate available published data on injuries that occur
in the sport of men's lacrosse at the youth, high school, collegiate, and
professional levels. METHODS: A comprehensive literature search was performed in
PubMed, High Wire Press, SPORTDiscus, Google Scholar, and Ovid, using the
keywords Lacrosse Injuries, Epidemiology Lacrosse Injuries, Lacrosse Injury,
Lacrosse AND Injury and limited to 1990-2016. All bibliographies were cross
referenced to identify any additional publications. Sources were categorized
based on data provided and were aggregated into groups based on reported overall
injury rates, rates by setting (competition vs. practice), nature of injury,
location, type, severity, and player position. RESULTS: The game and practice
injury rates in college are greater than the rates in high school, similarly
rates greater for high school players than in youth leagues. Rates of injury
varied from 0.095-12.98 per 1000 athlete exposures. Game injury rates were higher
across all studies. Injuries in men's lacrosse occur most often from player-to
player contact, which result in immediate injuries, such as concussions,
contusions, and lacerations. Overall concussion incidence was reported to range
from 0.11-0.84 per 1000 AE. The most common types of injuries were sprain,
strain, concussion, and contusions and the most common area of injury was hand
(23%), with a significant proportion of these (59.4%) being to the thumb. Limited
evidence of different injuries among the player positions suggests there might be
a pattern that midfield players had the most injuries, followed by offensive
players and then defensive players. CONCLUSIONS: The potential for sports-related
injury is of relative concern; especially considering rising participation and
total number of injuries. Further development and proper enforcement of safety
rules on player contact and protective equipment are recommended to decrease the
rate of lacrosse-related injury. Additional longitudinal research is needed to
better classify and to ultimately predict lacrosse injury factors and mechanisms
across all levels of play.
PMID- 28707499
TI - Performance of wells score to predict deep vein thrombosis and pulmonary embolism
in endurance athletes.
AB - INTRODUCTION: There are an increasing number of reports describing deep vein
thrombosis (DVT) and/or pulmonary embolism (PE) in otherwise healthy endurance
athletes. The Wells score is the most commonly used clinical prediction rule to
diagnose DVT/PE in clinical populations. However, the Wells score may have
limited utility for recognition of DVT/PE in athletes, contributing to missed or
delayed diagnosis. OBJECTIVE: We performed an analysis of the ability of the
Wells score to identify DVT/PE events in athletes through a review of published
case reports. METHODS: A systematic search of the literature yielded 11 case
reports. RESULTS: The Wells score had a 100% failure rate in identifying athletes
with DVT (0/6) and PE (0/5), resulting in a delayed diagnosis for DVT of 20 +/-
14 days. Retrospectively removing 'differential diagnosis' from the clinical
prediction rule for DVT changed the Wells score median from 0 (range: -1 to 0) to
2 (range: 1 to 2); the threshold for predicting DVT as 'likely'. There were
limited clinical characteristics captured in the Wells score for PE that were
applicable to athletes, highlighting the need for reappraisal. Although the Wells
score failed to accurately triage athletes with known DVT and/or PE, the addition
of a D-dimer value (mean: 1566 +/- 758ng/dL) to the Wells score correctly
identified 9/9 athletes. CONCLUSIONS: The Wells score had a 100% failure rate for
triaging athletes with known DVT/PE. When performed, D-dimer adequately
facilitated the additional diagnostic testing required for a timely diagnosis of
DVT/PE in athletes. Improving awareness of an atypical presentation of thrombotic
events in athletes may reduce the widespread underestimation of DVT/PE among
athletes and facilitate the additional testing required for a timely diagnosis.
PMID- 28707500
TI - Noninvasive Imaging of Immune Checkpoint Ligand PD-L1 in Tumors and Metastases
for Guiding Immunotherapy.
AB - Immunotherapy holds great promise in cancer treatment. The challenges in
advancing immunotherapies lie in patient stratification and monitoring therapy.
Noninvasive detection of immune checkpoint ligand PD-L1 can serve as an important
biomarker for guidance and monitoring of immunotherapy. Here in, we provide an
overview of our efforts to develop clinically translatable PD-L1-specific imaging
agents for quantitative and real-time assessment of PD-L1 expression in tumor
microenvironment.
PMID- 28707501
TI - Investigating the Reliability and Factor Structure of Kalichman's "Survey 2:
Research Misconduct" Questionnaire: A Post Hoc Analysis Among Biomedical Doctoral
Students in Scandinavia.
AB - A precondition for reducing scientific misconduct is evidence about scientists'
attitudes. We need reliable survey instruments, and this study investigates the
reliability of Kalichman's "Survey 2: research misconduct" questionnaire. The
study is a post hoc analysis of data from three surveys among biomedical doctoral
students in Scandinavia (2010-2015). We perform reliability analysis, and
exploratory and confirmatory factor analysis using a split-sample design as a
partial validation. The results indicate that a reliable 13-item scale can be
formed (Cronbach's alpha = .705), and factor analysis indicates that there are
four reliable subscales each tapping a different construct: (a) general attitude
to misconduct (alpha = .768), (b) attitude to personal misconduct (alpha = .784),
(c) attitude to whistleblowing (alpha = .841), and (d) attitude to
blameworthiness/punishment (alpha = .877). A full validation of the questionnaire
requires further research. We, nevertheless, hope that the results will
facilitate the increased use of the questionnaire in research.
PMID- 28707502
TI - Appraisal of the Psychiatric Diagnostic Screening Questionnaire in a perinatal
cohort: The APrON study.
AB - BACKGROUND: Depression and anxiety are routinely screened as part of perinatal
care. However, other Axis 1 disorders and specific anxiety disorders are less
likely to be screened or assessed as part of obstetric care. The objective of
this study was to determine whether the Psychiatric Diagnostic Screening
Questionnaire (PDSQ) is a potentially useful tool to screen for psychiatric
conditions in pregnant and postpartum women in a community setting. METHODS: We
compared the prevalence of DSM Axis I disorders obtained on the PDSQ with: (1)
the prevalence of these disorders reported in previous studies of pregnant and
postpartum women, and (2) scores obtained on the Edinburgh Postpartum Depression
Scale (EPDS) and the Symptom Checklist-90-Revised (SCL-90R) anxiety scale. Data
were obtained from the Alberta Pregnancy Outcomes and Nutrition (APrON) study.
RESULTS: The PDSQ was completed by 1575 women prenatally and 1481 postnatally.
The three most prevalent PDSQ conditions were social phobia, somatic disorder,
and obsessive-compulsive disorder (OCD). The prevalence of social phobia, alcohol
disorder, OCD and psychosis were higher in the APrON cohort compared with
statistics in the literature. The proportion of women meeting depression and
anxiety cut-offs on the PDSQ were lower than for the EPDS and the SCL-90R. The
Cohens Kappa index ( k) indicated poor to fair agreement between the measures in
classifying pregnant women as depressed or anxious. CONCLUSIONS: The PDSQ
subscales may not be appropriate for the pregnant population. Research into
instruments more specific to pregnant and postpartum women are needed to
determine the prevalence of psychiatric disorders in this population.
PMID- 28707503
TI - Two-way partial AUC and its properties.
AB - Simultaneous control on true positive rate and false positive rate is of
significant importance in the performance evaluation of diagnostic tests. Most of
the established literature utilizes partial area under receiver operating
characteristic (ROC) curve with restrictions only on false positive rate (FPR),
called FPR pAUC, as a performance measure. However, its indirect control on true
positive rate (TPR) is conceptually and practically misleading. In this paper, a
novel and intuitive performance measure, named as two-way pAUC, is proposed,
which directly quantifies partial area under ROC curve with explicit restrictions
on both TPR and FPR. To estimate two-way pAUC, we devise a nonparametric
estimator. Based on the estimator, a bootstrap-assisted testing method for two
way pAUC comparison is established. Moreover, to evaluate possible covariate
effects on two-way pAUC, a regression analysis framework is constructed.
Asymptotic normalities of the methods are provided. Advantages of the proposed
methods are illustrated by simulation and Wisconsin Breast Cancer Data. We encode
the methods as a publicly available R package tpAUC.
PMID- 28707504
TI - Behavioral Executive Functions Among Adolescents With Mathematics Difficulties.
AB - This study investigates behavioral executive functions (EFs) in the mathematics
classroom context among adolescents with different mathematics performance
levels. The EF problems were assessed by teachers using a behavioral rating
inventory. Using cutoff scores on a standardized mathematics assessment, groups
with mathematics difficulties (MD; n = 124), low mathematics performance (LA; n =
140), and average or higher scores (AC; n = 355) were identified. Results showed
that the MD group had more problems with distractibility, directing attention,
shifting attention, initiative, execution of action, planning, and evaluation
than the LA group, whereas the differences in hyperactivity, impulsivity, and
sustaining attention were not significant. Compared to the AC group, the MD group
showed more problems with all behavioral EFs except hyperactivity and
impulsivity, while the LA group showed more problems only with shifting
attention. Male adolescents showed more behavioral EF problems than female
adolescents, but this gender difference was negligible within the MD group. The
practical implications of the results are discussed.
PMID- 28707505
TI - Biomechanical analysis of the thoracolumbar spine under physiological loadings:
Experimental motion data corridors for validation of finite element models.
AB - Biomechanical studies that involve normal, injured or stabilized human spines are
sometimes difficult to perform on large samples due to limited access to
cadaveric human spines and biological variability. Finite element models
alleviate these limitations due to the possibility of reusing the same model,
whereas cadaveric spines can be damaged during testing, or have their mechanicals
behaviour modified by fatigue, permanent deformation or structural failure.
Finite element models need to be validated with experimental data to make sure
that they represent the complex mechanical and physiological behaviour of normal,
injured and stabilized spinal segments. The purpose of this study is to
characterize the mechanical response of thoracolumbar spine segments with an
analytical approach drawn from experimental measurements. A total of 24 normal
and fresh cadaveric thoracolumbar spine segments (T11-L3), aged between 53 and 91
years, were tested in pure flexion/extension, lateral bending and axial torsion
using a specific experimental setup. Measurements of global and intervertebral
angle variations were performed using three-dimensional mark tracking methods.
Load/angle curves for each loading were fitted by a logarithmic approach with two
coefficients. The coefficients for the functions describing the response of the
spinal segments are given and constitute predictive models from experimental
data. This work provides data corridors of human thoracolumbar spine motion
segments subjected to pure bending in the three physiological planes. These data
could be very useful to validate finite element models of the human spine.
PMID- 28707506
TI - Perception-action coupling in complex game play: Exploring the quiet eye in
contested basketball jump shots.
AB - The duration of the final fixation before movement initiation - a gaze strategy
labelled quiet eye - has been found to explain differences in motor expertise and
performance in precision tasks. To date, research only addressed this phenomenon
in situations without adversarial constraints. In the present study, we compared
the quiet-eye behaviour of intermediately-skilled and highly-skilled basketball
players in defended vs. undefended game situations. We predicted differences in
quiet-eye duration as a function of skill and performance particularly resulting
from late quiet-eye offsets. Results indicated performance-enhancing effects of
long quiet-eye durations in the defended but not in the undefended game
situation. Furthermore, in line with our prediction, later quiet-eye offsets were
associated with superior performance elucidating the phenomenon's relevance in
online-demanding motor tasks. Further, earlier quiet-eye onsets were linked to
successful performance supporting earlier suggestions that it is not only the
duration but also the timing that matters. These findings not only extend the
positive effects of the quiet eye in motor performance to dynamic game-play
situations but also support the role of the quiet eye in response to programming
and information processing respectively.
PMID- 28707507
TI - Marketplace Clinics Complementing Diabetes Care for Urban Residing American
Indians.
AB - INTRODUCTION: For several decades, the Minneapolis American Indian population has
experienced limited health care access and threefold diabetes health disparity.
As part of an urban health initiative, the marketplace clinics located in nearby
CVS, Target, and Supervalu stores committed financial support, providers,
certified educators, and pharmacy staff for a community-based diabetes support
group. OBJECTIVES: To measure the extent to which collaborating marketplace
clinics and the community-based support group expanded diabetes care and provided
self-management education for this largely urban Indian neighborhood. METHODS: A
controlled quasi-experimental study and 3-years retrospective analysis of
secondary data were used to test whether the Minneapolis marketplace clinics and
the community diabetes support group participants (n = 48) had improved diabetes
health outcomes relative to the comparison group (n = 87). The marketplace
complemented intervention group employed motivational interviewing and the
patient activation measure (PAM(r)) in coaching diabetes self-care and behavioral
modification. The federally funded comparison group received only basic self
management education. RESULTS: T tests and effect sizes were used to quantify the
difference between the study intervention and comparison groups. Statistical
significance was determined for the following outcome variables: A1C ( P < .01),
body mass index ( P < .04), and PAM(r) ( P < .001). DISCUSSION: Includes
strengths, limitations, and future study recommendations. CONCLUSIONS: Positive
effects of marketplace clinics and community health complementation were found
with regard to improved blood glucose control, weight loss, and healthful
lifestyle adaptation. Primary care and community health improvements could be
realized by incorporating patient activation with diabetes prevention programs
for the urban Indian two-thirds majority of the United States 5 million American
Indian population.
PMID- 28707508
TI - Design and fabrication of porous biodegradable scaffolds: a strategy for tissue
engineering.
AB - Current strategies of tissue engineering are focused on the reconstruction and
regeneration of damaged or deformed tissues by grafting of cells with scaffolds
and biomolecules. Recently, much interest is given to scaffolds which are based
on mimic the extracellular matrix that have induced the formation of new tissues.
To return functionality of the organ, the presence of a scaffold is essential as
a matrix for cell colonization, migration, growth, differentiation and
extracellular matrix deposition, until the tissues are totally restored or
regenerated. A wide variety of approaches has been developed either in scaffold
materials and production procedures or cell sources and cultivation techniques to
regenerate the tissues/organs in tissue engineering applications. This study has
been conducted to present an overview of the different scaffold fabrication
techniques such as solvent casting and particulate leaching, electrospinning,
emulsion freeze-drying, thermally induced phase separation, melt molding and
rapid prototyping with their properties, limitations, theoretical principles and
their prospective in tailoring appropriate micro-nanostructures for tissue
regeneration applications. This review also includes discussion on recent works
done in the field of tissue engineering.
PMID- 28707509
TI - Intestinal absorption of pallidifloside D are limited by P-glycoprotein in mice.
AB - 1. Pallidifloside D, a saponin glycoside constituent from the total saponins of
Smilax riparia, had been proved to be very effective in hyperuricemic control.
But it is poorly bioavailable after oral administration. Here, we determined the
role of P-glycoprotein (P-gp) in the intestinal absorption of Pallidifloside D.
2. We found that Pallidifloside D significantly stimulated P-gp ATPase activity
in vitro ATPase assay with a small EC50 value of 0.46 MUM. 3. In the single-pass
perfused mouse intestine model, the absorption of Pallidifloside D was not
favored in the small intestine (duodenum, jejunum and ileum) with a P*w value of
0.35-0.78. By contrast, this compound was well-absorbed in the colon with a P*w
value of 1.23. The P-gp inhibitors cyclosporine significantly enhanced
Pallidifloside D absorption in all four intestinal segments (duodenum, jejunum,
ileum and colon) and the fold change ranged from 5.5 to 15.3. Pharmacokinetic
study revealed that cyclosporine increased the systemic exposure of
Pallidifloside D by a 2.5-fold after oral administration. 4. These results
suggest that P-gp-mediated efflux is a limiting factor for intestinal absorption
of Pallidifloside D in mice.
PMID- 28707510
TI - Outcomes of sympathectomy and vascular bypass for digital ischaemia in connective
tissue disorders.
AB - : All patients (36 hands) with connective tissue disorders who underwent
periarterial sympathectomy of the hand alone or in conjunction with vascular
bypass at our institution between 1995-2013 were reviewed. The durable resolution
of ulcers was significantly higher in patients treated by periarterial
sympathectomy and bypass than in patients treated by periarterial sympathectomy
alone. Although there were more digital amputations in patients treated by
periarterial sympathectomy alone, the difference was not statistically
significant. Vascular bypass in conjunction with sympathectomy may be better than
sympathectomy alone in patients with digital ischaemia related to connective
tissue disorders. LEVEL OF EVIDENCE: IV.
PMID- 28707511
TI - Maternal fertility problems and risk for transient neonatal diabetes mellitus.
AB - AIMS: The study of imprinting disorders in the context of infertility and its
treatment is important, as studies have indicated an increased risk. In this
study, we evaluated the risk of transient neonatal diabetes mellitus (TNDM),
defined here as diabetes mellitus presenting within the first six weeks of life,
in children born to women with fertility problems. METHODS: This nationwide
register-based cohort study comprised all 2,107,837 children born in Denmark
between 1977 and 2010. Of these, 121,044 (5.7%) children were born to women with
fertility problems. Cox proportional hazards models were used to estimate hazard
ratios (HRs) and 95% confidence intervals (CIs) for the association between
maternal fertility status and the risk for TNDM. RESULTS: A total of 103 children
developed TNDM during the follow-up period. Children born to women with fertility
problems had an elevated risk for TNDM, after adjustment for birth year, maternal
age at birth and parental history of diabetes, although this was not
statistically significant (HR = 1.49; 95% CI 0.73-3.03). The risk of children
born in the period 1994-2010 (a period with more comprehensive information on
maternal fertility problems and with more invasive fertility treatment
procedures) was increased almost twofold (HR = 1.92; 95% CI 0.92-4.00) but was
still not statistically significant. CONCLUSIONS: Our results indicate that
children born to women with fertility problems, particularly after 1993, may be
at an elevated risk for TNDM. As the increased risks were not statistically
significant, however, the finding may be due to chance.
PMID- 28707512
TI - A commentary on the subclinical volume -overload in stable -outpatients with
chronic heart failure.
PMID- 28707513
TI - Cross-cultural adaptation and validation of the Danish 10-item Connor-Davidson
Resilience Scale among hospital staff.
AB - OBJECTIVES: The 10-item Connor-Davidson Resilience Scale (CD-RISC 10) is a brief
instrument measuring resilience in adults. The scale has shown sound psychometric
properties in different populations and cultures. Our objectives were to cross
culturally adapt the CD-RISC 10 into Danish and to establish the psychometric
properties of the Danish version in terms of internal consistency, construct
validity and longitudinal validity. METHODS: The CD-RISC 10 was translated using
established guidelines. Employees ( N=272) at hospitals in the Central Denmark
Region completed questionnaires at baseline and three months follow-up.
Questionnaires included the translated Danish version of the CD-RISC 10 and the
10-item Perceived Stress Scale (PSS-10). Internal consistency was assessed by
Cronbach's alpha and construct and longitudinal validity by correlating CD-RISC
10 and PSS-10 baseline scores and change scores from baseline to follow-up.
RESULTS: The Danish CD-RISC 10 provides acceptable internal consistency
(Cronbach's alpha = 0.87). Analysis of construct validity revealed a negative
correlation with the PSS-10 at baseline ( r=-.63 [95%CI: -.70; -.55], p<.0001).
Analysis of longitudinal validity similarly demonstrated a negative correlation
on change scores from baseline to follow-up ( r=-.51 [95%CI: -.62; -.39],
p<.0001). CONCLUSIONS: The scale has acceptable psychometric properties as an
instrument for measuring resilience in a Danish-speaking population.
PMID- 28707514
TI - Removal of estrone, 17beta-estradiol, and estriol from sewage and cow dung by
immobilized Novosphingobium sp. ARI-1.
AB - Immobilized bacterial agents (IBA) can increase the cell density and improve the
environmental adaptability of bacteria. An estrogen-degrading bacterium,
Novosphingobium sp. ARI-1, was immobilized in calcium alginate (CA) using an
embedding method and applied to the removal of estrogens from natural sewage and
cow dung. The optimum immobilization conditions were as follows: sodium alginate
(SA) and CaCl2.2H2O concentrations of 5% (m/v) and 4% (m/v), respectively; a
bacterial suspension to SA ratio of 1:2; and cross-linking for 6 h at 4 degrees
C. Immobilized strain ARI-1 mediated the biodegradation of estrone (E1), 17beta
estradiol (E2), and estriol (E3) either individually or in combination and was
tolerant of various temperatures and pH values. Immobilized ARI-1 removed 80.43%,
94.76%, and 100% of E1, E2, and E3 from sewage containing 1.75, 0.71, and 1.52
MUg L-1 of the three test estrogens within seven days, respectively. In cow dung
containing initial E1, E2, and E3 concentrations of 0.71, 0.64, and 0.66 mg kg-1,
respectively, E1 and E2 concentrations were below the limit of detection, and
1.09% of E3 remained after incubation with immobilized ARI-1 for seven days.
These results confirmed the utility of immobilized strain ARI-1 for the removal
of estrogens from environmental matrices.
PMID- 28707515
TI - Successful repositioning of leadless cardiac pacemaker during open heart surgery.
PMID- 28707516
TI - Anaerobic decolorization and detoxification of cationic red X-GRL by Shewanella
oneidensis MR-1.
AB - The ability of an electrochemically active bacterium, Shewanella oneidensis MR-1,
to decolorize azo dye cationic red X-GRL (X-GRL) was investigated. S. oneidensis
MR-1 showed a high decolorization capability for X-GRL under anaerobic
conditions. The Mtr respiratory pathway was proved to be involved in the
extracellular decolorization of X-GRL. The decolorization efficiency of S.
oneidensis MR-1 was significantly inhibited when the initial X-GRL concentration
was over 200 mg L-1. Increasing the inoculum volume of S. oneidensis MR-1 could
obviously promote the X-GRL decolorization. The 100 mg L-1 X-GRL and 6% (v/v)
inoculum volume were chosen as the optimal parameter. Under such a condition,
almost all of X-GRL (100 mg L-1) could be completely reduced after 12-h
incubation at the pH range of 5.5-8.0 and temperature range of 30-40 degrees C.
Salinity in the medium also affected X-GRL decolorization. Lactate and citric
acid were found to be the suitable electron donors for X-GRL decolorization.
Although the genotoxicity increased slightly, the phytotoxicity of X-GRL in the
decolorization process was significantly reduced by S. oneidensis MR-1.
PMID- 28707517
TI - Joint effect of triclosan and copper nanoparticles on wastewater biological
nutrient removal.
AB - Triclosan (TCS) is widely used in household and personal care products, and its
release into wastewater might have impact on wastewater biological treatment for
its antibacterial property. Besides, emerging pollutant such as copper
nanoparticles (CuNPs) will also release from nanoparticle-containing products,
showing a joint effect with TCS on biological nutrient removal. The TCS of 1 and
10 mg/L inhibited the nitrosification and nitrification stage, and the first step
of denitrification was suppressed as well, causing a decline in final TN removal
efficiency. Additionally, the phosphorus uptake was inhibited seriously, leading
to a remarkable decrease in phosphorus removal efficiency. When they were co
existed, the TCS concentration decreased due to the absorption by CuNPs, and the
released Cu2+ from CuNPs increased. Further investigation revealed that when 5
mg/L CuNPs and 1 mg/L TCS were immediately added to the activated sludge, the
final joint toxicity was similar to the individual effect of 1 mg/L TCS, while 10
mg/L CuNPs contributed to the final stronger toxicity. When TCS was sufficiently
reacted with CuNPs in wastewater, their final toxicity to activated sludge was
enhanced because the extent of toxicity relief caused by decrease in TCS
concentration was less than the degree of deteriorating effect due to the
promotion of Cu2+ release from CuNPs.
PMID- 28707519
TI - Obituary.
PMID- 28707518
TI - Interaction of copper (II) complexes by bovine serum albumin: spectroscopic and
calorimetric insights.
AB - Serum albumins being the most abundant proteins in the blood and cerebrospinal
fluid are significant carriers of essential transition metal ions in the human
body. Studies of copper (II) complexes have gained attention because of their
potential applications in synthetic, biological, and industrial processes. Study
of binding interactions of such bioinorganic complexes with serum albumins
improves our understanding of biomolecular recognition process essential for
rational drug design. In the present investigation, we have applied quantitative
approach to explore interactions of novel synthesized copper (II) complexes viz.
[Cu(L1)(L2)ClO4] (complex I), [Cu(L2)(L3)]ClO4] (complex II) and [Cu(L4)2(H2O)2]
(complex III) with bovine serum albumin (BSA) to evaluate their binding
characteristics, site and mode of interaction. The fluorescence quenching of BSA
initiated by complexation has been observed to be static in nature. The binding
interactions are endothermic driven by entropic factors as confirmed by high
sensitivity isothermal titration calorimetry. Changes in secondary and tertiary
structure of protein have been studied by circular dichroism and significant
reduction in alpha-helical content of BSA was observed upon binding. Site marking
experiments with warfarin and ibuprofen indicated that copper complexes bind at
site II of the protein.
PMID- 28707520
TI - Who are the lonely? A typology of loneliness in New Zealand.
AB - BACKGROUND: Loneliness has many negative physical and mental health ramifications
and is most prevalent among vulnerable social groups. However, little is known
about how loneliness is grouped within the population and the characteristics of
those groups. METHODS: We conducted a Latent Profile Analysis on 18,264
participants from the fifth wave of the New Zealand Attitudes and Values Study to
identify the number of distinct loneliness profiles in the population. Secondary
analyses then determined the representation of various demographic and
psychosocial characteristics of participants within each profile. RESULTS:
Analyses identified four distinct loneliness profiles: 'high-loneliness' (5.7%),
'low-loneliness' (57.9%), 'appreciated outsiders' (29.1%; who received acceptance
from others but felt like social outsiders) and 'superficially connected' (7.2%;
who showed the opposite pattern). 'High-loneliness' were the most introverted,
emotionally unstable and poorest in wellbeing. 'Appreciated outsiders' and
'superficially connected' had moderate wellbeing, but 'appreciated outsiders'
were relatively higher in wellbeing despite greater introversion and neuroticism.
CONCLUSION: This research provides a typology of loneliness in New Zealand and
identifies groups more likely to experience loneliness. The 'appreciated
outsiders' and 'superficially connected' profiles provide fresh insight into how
loneliness may manifest and the relative influences of quality and quantity of
social contacts on wellbeing.
PMID- 28707521
TI - Increased risk of attempted suicide in Australian veterans is associated with
total and permanent incapacitation, unemployment and posttraumatic stress
disorder severity.
AB - BACKGROUND: Military veterans have higher rates of suicidality and completed
suicides compared to the general population. Previous research has demonstrated
suicidal behaviour is higher in US combat veterans who are younger, suffer from
posttraumatic stress disorder, depression and anxiety and score lower on measures
of health. However, research on predictors of suicide for Australian veterans is
limited. The aim of this study was to identify significant demographic and
psychological differences between veterans with posttraumatic stress disorder who
had attempted suicide and those with posttraumatic stress disorder who had not,
as well as determine predictors of suicide attempts within an Australian cohort.
METHODS: A retrospective analysis was conducted on 229 ex-service personnel
diagnosed with posttraumatic stress disorder who had attended a Military Service
Trauma Recovery Day Program as outpatients at Toowong Private Hospital from 2007
to 2014. Patients completed a battery of mental health self-report questionnaires
assessing symptoms of posttraumatic stress disorder, alcohol use, anger,
depression, anxiety and quality of life. Demographic information and self
reported history of suicide attempts were also recorded. RESULTS: Results
indicated the average age was significantly lower, and the rates of posttraumatic
stress disorder, anger, anxiety and depression symptoms were significantly higher
in those veterans with history of a suicide attempt. Multivariate logistic
regression analyses indicated posttraumatic stress disorder symptom severity,
unemployment or total and permanent incapacity pension status significantly
predicted suicide attempt history. CONCLUSION: Among a cohort of Australian
veterans with posttraumatic stress disorder, psychopathology severity,
unemployment and total and permanent incapacity status are significantly
associated with suicidality. This study highlights the importance of early
identification of posttraumatic stress disorder and psychopathology, therapeutic
and social engagement, and prioritisation of tangible employment options or
meaningful and goal-directed activities for veterans deemed unable to work.
PMID- 28707522
TI - The effect of endothelin receptor antagonists in the endotoxin-induced uveitis
rabbit model.
AB - PURPOSE: To investigate the effect of Bosentan (non-selective endothelin receptor
antagonist) and BQ123 (ETA receptor antagonist) on intraocular inflammation in an
endotoxin-induced uveitis (EIU) rabbit model. METHODS: Uveitis was induced by
intravitreal injection of lipopolysaccharide (LPS). The animals were divided into
7 groups and there were six rabbits in each group (saline, saline and ethanol,
bosentan, BQ123, lipopolysaccharide (LPS), bosentan and LPS, BQ123 and LPS
injected groups). Bosentan and BQ123 were applied before LPS injection. Aqueous
humour was collected at 24th hour post-injections and enucleation was performed
for the evaluation of histopathological changes. RESULTS: BQ123 decreased
clinical score, cell counts and protein amount more than bosentan and it was
significant for cell counts (p = 0.018). Bosentan significantly diminished
inflammatory reactions more than BQ123 as shown in histopathological specimens (p
= 0.002). CONCLUSIONS: ETA receptor blockage is effective on uveitis treatment by
its protective effect on blood aqueous barrier.
PMID- 28707523
TI - Strut analysis for osteoporosis detection model using dental panoramic
radiography.
AB - OBJECTIVES: The aim of this study was to identify variables that can be used for
osteoporosis detection using strut analysis, fractal dimension (FD) and the gray
level co-occurrence matrix (GLCM) using multiple regions of interest and to
develop an osteoporosis detection model based on panoramic radiography. METHODS:
A total of 454 panoramic radiographs from oral examinations in our dental
hospital from 2012 to 2015 were randomly selected, equally distributed among
osteoporotic and non-osteoporotic patients (n = 227 in each group). The
radiographs were classified by bone mineral density (T-score). After 3 marrow
regions and the endosteal margin area were selected, strut features, FD and GLCM
were analysed using a customized image processing program. Image upsampling was
used to obtain the optimal binarization for calculating strut features and FD.
The independent-samples t-test was used to assess statistical differences between
the 2 groups. A decision tree and support vector machine were used to create and
verify an osteoporosis detection model. RESULTS: The endosteal margin area showed
statistically significant differences in FD, GLCM and strut variables between the
osteoporotic and non-osteoporotic patients, whereas the medullary portions showed
few distinguishing features. The sensitivity, specificity, and accuracy of the
strut variables in the endosteal margin area were 97.1%, 95.7 and 96.25 using the
decision tree and 97.2%, 97.1 and 96.9% using support vector machine, and these
were the best results obtained among the 3 methods. Strut variables with FD
and/or GLCM did not increase the diagnostic accuracy. CONCLUSION: The analysis of
strut features in the endosteal margin area showed potential for the development
of an osteoporosis detection model based on panoramic radiography.
PMID- 28707524
TI - Applicability of Cameriere's and Drusini' s age estimation methods to a sample of
Turkish adults.
AB - OBJECTIVES: The aim of this study was to investigate the applicability of
Drusini's and Cameriere's methods to a sample of Turkish people. METHODS:
Panoramic images of 200 individuals were allocated into two groups as study and
test groups and examined by two observers. Tooth coronal indexes (TCI), which is
the ratio between coronal pulp cavity height and crown height, were calculated in
the mandibular first and second premolars and molars. Pulp/tooth area ratios
(ARs) were calculated in the maxillary and mandibular canine teeth. Study group
measurements were used to derive a regression model. Test group measurements were
used to evaluate the accuracy of the regression model. Pearson's correlation
coefficients and regression analysis were used. RESULTS: The correlations between
TCIs and age were -0.230, -0.301, -0.344 and -0.257 for mandibular first
premolar, second premolar, first molar and second molar, respectively. Those for
the maxillary canine (MX) and mandibular canine (MN) ARs were -0.716 and -0.514,
respectively. The MX ARs were used to build the linear regression model that
explained 51.2% of the total variation, with a standard error of 9.23 years. The
mean error of the estimates in test group was 8 years and age of 64% of the
individuals were estimated with an error of <+/-10 years which is acceptable in
forensic age prediction. CONCLUSIONS: The low correlation coefficients between
age and TCI indicate that Drusini's method was not applicable to the estimation
of age in a Turkish population. Using Cameriere's method, we derived a regression
model.
PMID- 28707525
TI - Is there a role for ultrasound-guided balloon sialoplasty technique in salivary
gland structures.
AB - Ductal stricture is a common cause of obstructive salivary gland disease. Balloon
dilatation of the parotid duct as a minimally invasive technique is currently
carried out under fluoroscopic guidance or during sialendocopy. We present a case
report of ultrasound-guided balloon dilatation. A 45-year-old female presented
with a long history of obstructive symptoms affecting the right parotid gland.
Ultrasound examination revealed a tortuous right main parotid duct with marked
dilatation throughout its course and multiple sites of focal stricture formation.
A sialogram was carried out to further characterize the ductal system, it showed
significant dilatation of the main duct but due to overlapping of the elements of
sialodochitis the visualization of the location and presence of strictures was
very difficult. It was felt that ultrasound would be a better imaging modality to
utilize in order to guide balloon dilatation of the strictures. Therefore, a
balloon dilatation was carried out under ultrasound guidance. The main advantage
of this technique is to preserve the physician and the patient from radiation
exposure. In our knowledge this is the first case reported yet in the literature.
PMID- 28707526
TI - Diagnostic validity of periapical radiography and CBCT for assessing periapical
lesions that persist after endodontic surgery.
AB - OBJECTIVES: Traditionally, healing after surgical endodontic retreatment (SER);
i.e. apicectomy with or without a retrograde filling, is assessed in periapical
radiographs (PR). Recently, the use of cone beam CT (CBCT) has increased within
endodontics. Generally, CBCT detects more periapical lesions than PR, but basic
research on the true nature of these lesions is missing. The objective was to
assess the diagnostic validity of PR and CBCT for determining inflammation in SER
cases that were re-operated (SER-R) due to unsuccessful healing, using histology
of the periapical lesion as reference for inflammation. METHODS: Records from 149
patients, receiving SER 2004-10, were screened. In total 108 patients (119 teeth)
were recalled for clinical follow-up examination, PR and CBCT, of which 74
patients (83 teeth) participated. Three observers assessed PR and CBCT as
"successful healing" or "unsuccessful healing" using Rud and Molven's criteria.
SER-R was offered to all non-healed teeth with expected favourable prognosis for
subsequent functional retention. During SER-R, biopsy was performed and
histopathology verified whether or not inflammation was present. RESULTS: All re
operated cases were assessed non-healed in CBCT while 11 of these were assessed
successfully healed in PR. Nineteen biopsies were examined. Histopathologic
diagnosis revealed 42% (teeth = 8) without periapical inflammation, 16% (teeth =
3) with mild inflammation and 42% (teeth = 8) with moderate to intense
inflammation. A correct diagnosis was obtained in 58% with CBCT (true positives)
and 63% with PR (true positives+true negatives). CONCLUSIONS: Of the re-operated
teeth, 42% had no periapical inflammatory lesion, and hence no benefit from SER
R. Not all lesions observed in CBCT represented periapical inflammatory lesions.
PMID- 28707528
TI - Whole-body MRI in the early detection of multifocal osteonecrosis.
PMID- 28707527
TI - Diagnostic usefulness of low-dose lumbar multi-detector CT with iterative
reconstruction in trauma patients: acomparison with standard-dose CT.
AB - OBJECTIVE: To compare the image quality (IQ), radiation dose and diagnostic
reliability of standard-dose and low-dose lumbar spine (L-spine) multi-detector
CT (SDCT and LDCT, respectively) with iterative reconstruction (IR) in trauma
patients. METHODS: We retrospectively analysed the data of 263 consecutive
patients (male:female, 133:130; mean age, 44.3 years) who underwent SDCT (200
300mAs; 120 kVp) with IR (n = 126) or LDCT (80-150mAs; 120kVp) with IR (n = 137)
for suspected L-spine fractures between November 2015 and September 2016.
Patients were categorized according to their body mass index, as follows: Group
1,~22.9 kg m-2; Group 2, 23-24.9 kg m-2 or Group 3,>=25 kg m-2. We compared the
quantitative IQ (signal-to-noise ratio), qualitative IQ (subjective image noise
and diagnostic acceptability [4-point rating scale; score 1-4], image sharpness
[5-point rating scale; score 1-5]) and diagnostic accuracy between the two scan
types. Interobserver agreement was also calculated. RESULTS: Overall, SDCT
exhibited slightly better diagnostic performance than did LDCT (sensitivity, 96.7
100%vs94-98.5%; specificity, 95.6-97.0%vs both 95.7%; accuracy, 96.0-98.4%vs94.9
97.1%). However, none of these parameters was significantly different between
SDCT and LDCT, either in the whole cohort (p >= 0.50) or among the three body
mass index groups (p >= 0.49). All interobserver agreements were excellent or
good (range, 0.776-0.985). CONCLUSIONS: The diagnostic performance of LDCT with
IR for L-spine fractures was comparable to that of SDCT with IR, with a 47-69%
reduction in the radiation dose. Advances in knowledge: LDCT scan can be used as
a diagnostic imaging tool for evaluating trauma patients with suspected L-spine
fractures.
PMID- 28707529
TI - Interpretation of digital breast tomosynthesis: preliminary study on comparison
with picture archiving and communication system (PACS) and dedicated workstation.
AB - OBJECTIVE: To compare the diagnostic accuracy and efficiency in the
interpretation of digital breast tomosynthesis (DBT) images using a picture
archiving and communication system (PACS) and a dedicated workstation. METHODS:
97 DBT images obtained for screening or diagnostic purposes were stored in both a
workstation and a PACS and evaluated in combination with digital mammography by
three independent radiologists retrospectively. Breast Imaging-Reporting and Data
System final assessments and likelihood of malignancy (%) were assigned and the
interpretation time when using the workstation and PACS was recorded. Receiver
operating characteristic curve analysis, sensitivities and specificities were
compared with histopathological examination and follow-up data as a reference
standard. RESULTS: Area under the receiver operating characteristic curve values
for cancer detection (0.839 vs 0.815, p = 0.6375) and sensitivity (81.8% vs
75.8%, p = 0.2188) showed no statistically significant differences between the
workstation and PACS. However, specificity was significantly higher when
analysing on the workstation than when using PACS (83.7% vs 76.9%, p = 0.009).
When evaluating DBT images using PACS, only one case was deemed necessary to be
reanalysed using the workstation. The mean time to interpret DBT images on PACS
(1.68 min/case) was significantly longer than that to interpret on the
workstation (1.35 min/case) (p < 0.0001). CONCLUSION: Interpretation of DBT
images using PACS showed comparable diagnostic performance to a dedicated
workstation, even though it required a longer reading time. Advances in
knowledge: Interpretation of DBT images using PACS is an alternative to evaluate
the images when a dedicated workstation is not available.
PMID- 28707530
TI - Cartilage quantification using contrast-enhanced MRI in the wrist of rheumatoid
arthritis: cartilage loss is associated with bone marrow edema.
AB - OBJECTIVE: To quantify wrist cartilage using contrast MRI and compare with the
extent of adjacent synovitis and bone marrow edema (BME) in patients with
rheumatoid arthritis (RA). METHODS: 18 patients with RA underwent post-contrast
fat-suppressed T1weighted coronal imaging. Cartilage area at the centre of the
scaphoid-capitate and radius-scaphoid joints was measured by in-house developed
software. We defined cartilage as the pixels with signal intensity between two
thresholds (lower: 0.4, 0.5 and 0.6 times the muscle signal, upper: 0.9, 1.0,
1.1, 1.2 and 1.3 times the muscle signal). We investigated the association of
cartilage loss with synovitis and BME score derived from RA MRI scoring system.
RESULTS: Cartilage area was correlated with BME score when thresholds were
adequately set with lower threshold at 0.6 times the muscle signal and upper
threshold at 1.2 times the muscle signal for both SC (rs=-0.469, p < 0.05) and RS
(rs=-0.486, p < 0.05) joints, while it showed no significant correlation with
synovitis score at any thresholds. CONCLUSION: Our software can accurately
quantify cartilage in the wrist and BME associated with cartilage loss in
patients with RA. Advances in knowledge: Our software can quantify cartilage
using conventional MR images of the wrist. BME is associated with cartilage loss
in RA patients.
PMID- 28707532
TI - A novel diagnostic aid for intra-abdominal adhesion detection in cine-MR imaging:
Pilot study and initial diagnostic impressions.
AB - OBJECTIVES: A non-invasive diagnostic technique for abdominal adhesions is not
currently available. Capture of abdominal motion due to respiration in cine-MRI
has shown promise, but is difficult to interpret. This article explores the value
of a complimentary diagnostic aid to facilitate the non-invasive detection of
abdominal adhesions using cine-MRI. METHOD: An image processing technique was
developed to quantify the amount of sliding that occurs between the organs of the
abdomen and the abdominal wall in sagittal cine-MRI slices. The technique
produces a 'sheargram' which depicts the amount of sliding which has occurred
over 1-3 respiratory cycles. A retrospective cohort of 52 patients, scanned for
suspected adhesions, made 281 cine-MRI sagittal slices available for processing.
The resulting sheargrams were reported by two operators and compared to expert
clinical judgement of the cine-MRI scans. RESULTS: The sheargram matched clinical
judgement in 84% of all sagittal slices and 93-96% of positive adhesions were
identified on the sheargram. The sheargram displayed a slight skew towards
sensitivity over specificity, with a high positive adhesion detection rate but at
the expense of false positives. CONCLUSIONS: Good correlation between sheargram
and absence/presence of inferred adhesions indicates quantification of sliding
motion has potential to aid adhesion detection in cine-MRI. Advances in
Knowledge: This is the first attempt to clinically evaluate a novel image
processing technique quantifying the sliding motion of the abdominal contents
against the abdominal wall. The results of this pilot study reveal its potential
as a diagnostic aid for detection of abdominal adhesions.
PMID- 28707531
TI - Third version of vendor-specific model-based iterativereconstruction (Veo 3.0):
evaluation of CT image quality in the abdomen using new noise reduction presets
and varied slice optimization.
AB - OBJECTIVE: To qualitatively and quantitatively compare abdominal CT images
reconstructed with a newversion of model-based iterative reconstruction (Veo 3.0;
GE Healthcare Waukesha, WI) utilizing varied presetsof resolution preference,
noise reduction and slice optimization. METHODS: This retrospective study was
approved by our Institutional Review Board and was Health Insurance Portability
and Accountability Act compliant. The raw datafrom 30 consecutive patients who
had undergone CT abdomen scanning were used to reconstructfour clinical presets
of 3.75mm axial images using Veo 3.0: 5% resolution preference (RP05n), 5%noise
reduction (NR05) and 40% noise reduction (NR40) with new 3.75mm
"sliceoptimization," as well as one set using RP05 with conventional 0.625mm
"slice optimization" (RP05c). The images were reviewed by two independent readers
in a blinded, randomized manner using a 5-point Likert scale as well as a 5-point
comparative scale. Multiple two-dimensional circular regions of interest were
defined for noise and contrast-to-noise ratio measurements. Line profiles were
drawn across the 7 lp cm-1 bar pattern of the Catphan 600 phantom for evaluation
of spatial resolution. RESULTS: The NR05 image set was ranked as the best series
in overall image quality (mean difference inrank 0.48, 95% CI [0.081-0.88], p =
0.01) and with specific reference to liver evaluation (meandifference 0.46, 95%
CI [0.030-0.89], p = 0.03), when compared with the secondbest series ineach
category. RP05n was ranked as the best for bone evaluation. NR40 was ranked
assignificantly inferior across all assessed categories. Although the NR05 and
RP05c image setshad nearly the same contrast-to-noise ratio and spatial
resolution, NR05 was generally preferred. Image noise and spatial resolution
increased along a spectrum with RP05n the highest and NR40the lowest. Compared to
RP05n, the average noise was 21.01% lower for NR05, 26.88%lower for RP05c and
50.86% lower for NR40. CONCLUSION: Veo 3.0 clinical presets allow for selection
of image noise and spatial resolution balance; for contrast-enhanced CT
evaluation of the abdomen, the 5% noise reduction preset with 3.75 mm slice
optimization (NR05) was generally ranked superior qualitatively and, relative to
other series, was in the middle of the spectrum with reference to image noise and
spatial resolution. Advances in knowledge: To our knowledge, this is the first
study of Veo 3.0 noise reduction presets and varied slice optimization. This
study provides insight into the behaviour of slice optimization and documents the
degree of noise reduction and spatial resolution changes that users can expect
across various Veo 3.0 clinical presets. These results provide important
parameters to guide preset selection for both clinical and research purposes.
PMID- 28707533
TI - Role of extra cranial stereotactic body radiation therapy in the management of
Stage IV melanoma.
AB - OBJECTIVE: To investigate the role of extracranial stereotactic body radiation
therapy (SBRT) in the management of oligometastatic melanoma. METHODS: Patients
affected by Stage IV melanoma, with less than three extracranial metastatic
lesions, who received SBRT were included in this analysis. Acute and late
toxicity, local control (LC), overall survival (OS) and progression-free survival
(PFS) were analysed. RESULTS: 31 patients were included in the study. 16 patients
(51.6%) were treated for lung meta-stases, 8 patients for liver metastases
(25.8%) and 7 (22.6%) for nodal metastases. 38 lesions were irradiated. With a
median follow-up time of 13 months, 11 patients (35.4%) were still alive, in four
cases (12.9%) with no evidence of disease. Median OS was 10.6 months, and OS at
6, 12 and 24 months was 77, 41 and 21% respectively. LC at 12 and 24 months was
96.6 and 82.8%. 23 patients (74.2%) developed distant metastases. Median PFS was
5.8 months, and PFS at 6, 12 and 24 months was 48.2, 18.5 and 13.9% respectively.
Number of irradiated lesions showed a statistically significant correlation only
with LC (p = 0.03). Response of the irradiated lesion was related to OS (p =
0.019). Local response showed also a borderline correlation with PFS (p = 0.07).
CONCLUSION: SBRT for extracranial metastases from melanoma is feasible and well
tolerated. Response of the irradiated lesions is predictive of OS. Advances in
knowledge: SBRT for melanoma extracranial metastases is feasible and the response
of the irradiated lesions is predictive of OS.
PMID- 28707534
TI - Fosbury flop tear of the rotator cuff: diagnostic assessment with magnetic
resonance arthrography.
AB - OBJECTIVES: The aim was to assess the diagnostic performance of magnetic
resonance arthrography (MRA) of the shoulder for the detection of "Fosbury flop"
tears. METHODS: All patients undergoing arthroscopic rotator cuff repair were
considered as potentially eligible for inclusion in this prospective case series.
Preoperative MRAs were consecutively performed and compared with intraoperative
findings being the gold standard control. Two experienced musculoskeletal
radiologists, blinded to the arthroscopic findings, independently analysed all
MRAs for the presence of typical signs of Fosbury flop tears. RESULTS: 423
patients were included. Among this group, 11 presented a Fosbury flop tear with a
prevalence of 2.6%. Interobserver agreement was considered as excellent for
thickened tendon, tendon stump, fluid accumulation, abnormal fibres
orientationand adherences between tendon and bursa. The most sensitive and
specific criterion was the tendon thickness[90.9% CI(62.3-98.4) and97.1% CI(95.0
98.3), respectively]. Conclusions: Fosbury flop tear is an uncommon condition
that should be recognized to allow optimal anatomic repair. MRA is a valuable
tool in making the diagnosing of this lesser recognized type of rotator cuff
tear. An abnormally thickened supraspinatus tendon tear should especially raise
suspicion for a Fosbury flop tear of the posterosuperior rotator cuff. Advances
in knowledge: MRA is a valuable tool in making the diagnosing of Fosbury flop
tears. An abnormally thickened supraspinatus tendon tear should especially raise
suspicion for such lesion.
PMID- 28707535
TI - Anatomical and MR correlative study of the proximal sciatic nerve vasculature.
AB - OBJECTIVE: The aim of our study is to demonstrate that increased T2 signal on MRI
could be due to intraneural vessels in asymptomatic individuals, and may
therefore be a normal finding. METHODS: An initial anatomic cadaveric study was
undertaken to gain a better understanding of the vascular supply of the proximal
sciatic nerve. Secondly, a retrospective study of MR imaging of patients without
sciatic symptoms was performed to assess the prevalence of intraneural vessels,
defined as hyperintensity on at least three consecutive slices on both T2 and
gadolinium enhanced T1 weighted imaging, visible on routine MSK pelvic imaging.
RESULTS: The anatomical study demonstrated a relatively abundant blood supply in
the peri-ischiatic region. In the MR study, 20/76 (26%) patients showed visible
intraneural vessels. More than one intraneural vessel was depicted in two of the
sciatic nerves. Direct branching between the extrinsic and intrinsic systems was
seen in only five cases. CONCLUSION: Normal intraneural vessels can frequently be
seen within the sciatic nerve on routine musculoskeletal pelvic imaging. Advances
in knowledge: T2 hyperintensity in the proximal sciatic nerve can be due to
intraneural vessels and should not necessarily be reported as abnormal.
PMID- 28707536
TI - Radiation dose reduction in multidetector CT in fracture evaluation.
AB - OBJECTIVE: To evaluate whether multidetector CT with low-dose radiation (low-dose
CT) of joints can be useful when evaluating fractures. METHODS: Our study
included CT scans of 398 patients, 103 shoulder cases, 109 wrist cases, 98 pelvis
cases and 88 ankle cases. There were 191 females and 207 males. The low-dose CTs
were performed using identical voltage and parameters with the exception of
decreased (half of standard dose) tube current. Low-dose and standard-dose images
were compared with regards to objective image quality, subjective evaluation of
image quality and diagnostic performance for the fractures. RESULTS: There was no
significant difference of image noise between standard-dose CT and low-dose CT in
every joint (p > 0.05). Each mean value of subjective score did not show
significant difference according to the dosage of the CT scan. There were no
statistically significant differences in the sensitivity (96-100%), specificity
(95.2-100%) or accuracy (97.9-100%) between standard-dose CT and low-dose CT (p
values, 0.1336-1.000). CONCLUSION: The evaluation of extremities for fractures
using low-dose CT can reduce radiation exposure by about 50% compared with
standard-dose CT without affecting image quality or diagnostic performance.
Advances in knowledge: Low-dose CT of the extremities (shoulder, pelvis, ankle
and wrist) can reduce radiation dose by about 50% compared with standard-dose CT
and does not significantly affect image quality or diagnostic performance in
fracture detection.
PMID- 28707537
TI - A perspective on the impact of radiation therapy on the immune rheostat.
AB - The advent and success of immune checkpoint inhibitors (ICIs) in cancer treatment
has broadened the spectrum of tumours that might be considered "immunogenic" and
susceptible to immunotherapeutic (IT) intervention. Not all cancer types are
sensitive, and not all patients with any given type respond. Combination
treatment of ICIs with an established cytotoxic modality such as radiation
therapy (RT) is a logical step towards improvement. For one, RT alone has been
shown to be genuinely immunomodulatory and secondly pre-clinical data generally
support combined ICI-RT approaches. This new integrated therapy for cancer
treatment holds much promise, although there is still a lot to be learned about
how best to schedule the treatments, manage the toxicities and determine what
biomarkers might predict response, as well as many other issues. This review
examines how RT alters the immune rheostat and how it might best be positioned to
fully exploit IT.
PMID- 28707538
TI - Adrenal cortical hyperplasia: diagnostic workup, subtypes, imaging features and
mimics.
AB - Adrenal cortical hyperplasia manifests radiologically as a non-malignant growth,
or enlargement, of the adrenal glands, specifically the cortex, although the
cortex cannot be definitively identified by conventional imaging. Controlled by
the pituitary gland, the adrenal cortex drives critical processes, such as the
production of cortisol, mineralocorticoid and sex hormones. Any disruption in the
multiple enzymes and hormones involved in these pathways may cause serious or
life-threatening symptoms, often associated with anatomical changes in the
adrenal glands. Diagnosis and treatment of adrenal cortical hyperplasia requires
a thorough clinical evaluation. As imaging has become more robust so has its role
in the diagnosis and treatment of adrenal conditions. CT has been the primary
modality for adrenal imaging owing to reproducibility, temporal and spatial
resolution and broad access. MRI serves a complimentary role in adrenal imaging
and can be used to further evaluate indeterminate CT findings or serve as an
adjunct tool without the use of ionizing radiation. Ultrasound and fluoroscopy
(genitography) are most commonly used in children and foetuses to evaluate
congenital adrenal hyperplasia. This article will discuss the clinical
presentation, laboratory workup and imaging features of adrenal cortical
hyperplasia, both congenital and acquired.
PMID- 28707539
TI - Visceral adipose tissue area measurement at a single level: can it represent
visceral adipose tissue volume?
AB - OBJECTIVE: Measurement of visceral adipose tissue (VAT) needs to be accurate and
sensitive to change for risk monitoring. The purpose of this study is to
determine the CT slice location where VAT area can best reflect changes in VAT
volume and body weight. METHODS: 60 plain abdominal CT images from 30 males [mean
age (range) 51 (41-68) years, mean body weight (range) 71.1 (101.9-50.9) kg] who
underwent workplace screenings twice within a 1-year interval were evaluated.
Automatically calculated and manually corrected areas of the VAT of various scan
levels using "freeform curve" region of interest on CT were recorded and compared
with body weight changes. RESULTS: The strongest correlations of VAT area with
VAT volume and body weight changes were shown in a slice 3 cm above the lower
margin of L3 with r values of 0.853 and 0.902, respectively. CONCLUSION: VAT area
measurement at a single level 3 cm above the lower margin of the L3 vertebra is
feasible and can reflect changes in VAT volume and body weight. Advances in
knowledge: As VAT area at a CT slice 3cm above the lower margin of L3 can best
reflect interval changes in VAT volume and body weight, VAT area measurement
should be selected at this location.
PMID- 28707540
TI - Commentary on duty of candour and cancer screening.
AB - English law mandates a duty of candour (DOC) for all healthcare providers. They
must be open and honest when something goes wrong with care causing harm.
Providers must apologize to those affected and investigate what happened.
Screening is not 100% accurate and false positive and false negative results are
inevitable. Guidance on DOC assists providers to judge when something has gone
wrong in screening and the DOC legislation applies. DOC guidance helps
distinguish such incidents from harms that are an expected and inevitable
consequence of the imperfections of screening tests. For breast cancer screening
the classification of interval cancers has been updated to take account of DOC.
This guidance on DOC and classification of prior films of those presenting with
interval cancers has relevance to other areas of diagnostic imaging. Review of
prior examinations after a significant diagnosis has been made may reveal a
previously overlooked abnormality.
PMID- 28707541
TI - Concurrent weekly cisplatin versus triweekly cisplatin with radiotherapy for
locally advanced squamous-cell carcinoma of the cervix: a retrospective analysis
from a single institution.
AB - OBJECTIVE: To compare patients with cervical cancer who were primarily treated
with concurrent chemoradiotherapy (CCRT) using 20 mg m-2 CDDP for 5 days every 3
weeks with weekly regimens of 40 mg m-2. METHODS: We retrospectively analyzed 185
patients with Stage IB-IVA squamous-cell carcinoma of the cervix who were treated
with CCRT between 2005 and 2013 at our hospital. The CCRT regimen consisted of
cisplatin (CDDP) at 20 mg m-2 for 5 days every 3 weeks or 40 mg m-2 weekly,
administered concomitantly with RT. RESULTS: The median age was 50 years (range:
22-70 years) in the triweekly group and was 50.5 years (range: 28-70 years) in
the weekly group. The 5-year overall survival rate in the triweekly and weekly
groups were 82.0% and 83.3%, respectively (p = 0.851); their disease-free
survival rate was 79.6% and 78.1%, respectively (p = 0.672). In the triweekly
group, 56 patients (50.9%) had grade 3/4 leukopenia, which was significantly
higher than that of 11 patients (15%) in the weekly group (p < 0.0001).
CONCLUSION: The weekly CDDP regimen for CCRT seems better in patients with
International Federation of Gynecology and Obstetrics Stages IB-IVA squamous-cell
carcinoma of the cervix. Advances in knowledge: The weekly CDDP regimen for CCRT
seems better in patients with International Federation of Gynecology and
Obstetrics Stages IB-IVA squamous-cell carcinoma of the cervix.
PMID- 28707542
TI - The physiological consequences of different distributions of diffuse pleural
thickening on CT imaging.
AB - OBJECTIVE: Diffuse pleural thickening (DPT) refers to extensive visceral pleural
fibrosis with adhesion formation to the parietal pleura obliterating the pleural
space. The radiological definition of DPT remains controversial with most of the
literature requiring the presence of an obliterated costophrenic angle (CPA) for
defining DPT. We conducted a study to investigate the variable distributions of
DPT and associated lung function deficit. METHODS: 85 patients referred to a
pleural clinic with suspected pleural thickening were screened for our study.
Data were collected from 37 patients with DPT confirmed on CT by size criteria
(>=3 mm thick, >=5 cm wide and >=8 cm in length), and 21 controls with pleural
plaques but no other pleuroparenchymal pathology. 27 patients were excluded.
Groups were matched to age, body mass index and smoking history. RESULTS: The
percentage of predicted forced vital capacity showed a gradual decline from 98.9%
for the control group to 83.5% in the DPT without CPA obliteration group (p <
0.05), to 79.5% in the unilateral DPT group (p < 0.001) and 66.7% in the
bilateral group (p < 0.001). Similar reductions were seen in the percentage of
predicted total lung capacity in the DPT with no CPA obliteration group and the
bilateral DPT group. CONCLUSION: Our study shows an incremental reduction in the
forced vital capacity and total lung capacity in DPT without CPA obliteration,
unilateral and bilateral DPT when compared with a matched control group. Advances
in knowledge: Different distributions of DPT including no CPA obliteration can
cause respiratory impairment, with bilateral DPT being the worst affected.
PMID- 28707543
TI - PET/MRI-knocking on the doors of the rich and famous.
AB - Since 2010 the portfolio of positron emission tomography (PET)-based imaging has
been expanded by industry with the introduction of combined whole-body PET/MRI
systems with the intent of merging PET-based molecular imaging with the strengths
of MRI. PET/MRI has created a lot of hype in the scientific community but
comparatively little traction in the clinic. The first years of whole-body
PET/MRI were used to address inherent technical challenges; however, it is now
time to make use of the full potential of this integrated imaging modality. This
opinion piece highlights the continuing challenges for the clinical adoption of
PET/MRI and cautions against putting too much emphasis on comparisons with
clinical PET/CT. In order for PET/MRI to enter clinical practice, cross-specialty
co-operation must be pursued with rigour and use-case scenarios must be
propagated, following long-awaited expansion of reimbursement strategies and
protocol standardization.
PMID- 28707544
TI - Differentiation of chronic total occlusion and subtotal occlusion of the
femoropopliteal artery-role of retrograde flow sign and collateral circulation on
CT angiography images.
AB - OBJECTIVE: To study the value of a retrograde flow sign and the collateral
circulation on CT angiography (CTA) for the differential diagnosis of chronic
total occlusion from subtotal occlusion of the femoropopliteal artery (FPA). 50
patients with obstruction of the FPA underwent CTA and digital subtraction
angiography examinations of the lower limbs. The frequency of a retrograde flow
sign and collateral circulation on CTA in chronic total and subtotal occlusion
was noted and analyzed, with the results of digital subtraction angiography as a
standard to judge total or subtotal occlusion. The decreasing CT value from the
distal to proximal direction on CTA suggests the existence of retrograde flow.
RESULTS: There were significant differences in the occurrence rates of a
retrograde flow sign on CTA in the chronic total and subtotal obstruction groups
(X2 = 13.1, p < 0.05), as well as a collateral circulation sign (X2 = 13.5, p <
0.05). Employing both the retrograde flow sign and the collateral circulation
sign to diagnose chronic total obstruction of the FPA had a sensitivity of 92.3%
and specificity of 89.8%. CONCLUSION: The retrograde flow sign combined with a
collateral circulation sign is of great clinical value for differentiation of
chronic total stenosis from severe stenosis (subtotal occlusion) of the FPA.
Advances in knowledge: A retrograde flow sign combined with a collateral
circulation sign is of great clinical value to differentiate between chronic
total stenosis and severe stenosis (subtotal occlusion) of the FPA.
PMID- 28707545
TI - Diagnostic evaluation of simulation CT images for adjuvant radiotherapy in
pancreatic adenocarcinoma.
AB - OBJECTIVE: The purpose of this study is to review simulation CT scans and
evaluate their diagnostic value in patients treated with adjuvant radiotherapy
for pancreatic adenocarcinoma. METHODS: 73 patients who had undergone simulation
CT scans for adjuvant radiotherapy in pancreatic adenocarcinoma were reviewed.
All simulation CT scans were reviewed by professional abdominal radiologists, who
compared the images with corresponding prior CT scans to identify new lesions.
Newly detected cancer-related lesions were classified into one of three
categories: distant metastasis, locoregional recurrence and indeterminate
lesions. Indeterminate lesions were reviewed for malignancy during follow-up
imaging work-ups. RESULTS: Of 73 patients, distant metastasis, locoregional
recurrence and indeterminate lesions were found in 4 (5.5%), 5 (6.8%) and 32
patients (43.8%), respectively. Among 32 indeterminate lesions, 24 (75.0%) were
soft tissue lesions neighbouring the superior mesenteric vessels. Follow-up PET
CT and diagnostic CT scans revealed that 43.7% of indeterminate lesions were
malignant presenting local failures. The 3-year overall survival was
significantly higher among patients who had no cancer-related lesions than among
who did have such findings (44.8% vs 10.8%, p = 0.002). CONCLUSION: Professional
review of simulation CT scans have ample diagnostic value as they help detect
early progressions or potential failures in patients treated with adjuvant
radiotherapy for pancreatic adenocarcinoma. Simulation CT scans should be
carefully reviewed before the delivery of adjuvant radiotherapy. Advances in
knowledge: Generally, simulation CT scan has been known to provide limited
diagnostic values and clinical impact. However, the results of this study showed
a high detection rate of cancer-related lesions, which could potentially affect
subsequent treatment strategies in patients with pancreatic adenocarcinoma.
PMID- 28707546
TI - A computer-aided diagnosis (CAD) scheme for pretreatment prediction of
pathological response to neoadjuvant therapy using dynamic contrast-enhanced MRI
texture features.
AB - OBJECTIVE: To assess whether a computer-aided, diagnosis (CAD) system can predict
pathological Complete Response (pCR) to neoadjuvant chemotherapy (NAC) prior to
treatment using texture features. METHODS: Response to treatment of 44 patients
was defined according to the histopatology of resected tumour and extracted
axillary nodes in two ways: (a) pCR+ (Smith's Grade = 5) vs pCR- (Smith's Grade <
5); (b) pCRN+ (pCR+ and absence of residual lymph node metastases) vs pCRN - . A
CAD system was developed to: (i) segment the breasts; (ii) register the DCE-MRI
sequence; (iii) detect the lesion and (iv) extract 27 3D texture features. The
role of individual texture features, multiparametric models and Bayesian
classifiers in predicting patients' response to NAC were evaluated. RESULTS: A
cross-validated Bayesian classifier fed with 6 features was able to predict pCR
with a specificity of 72% and a sensitivity of 67%. Conversely, 2 features were
used by the Bayesian classifier to predict pCRN, obtaining a sensitivity of 69%
and a specificity of 61%. CONCLUSION: A CAD scheme, that extracts texture
features from an automatically segmented 3D mask of the tumour, could predict
pathological response to NAC. Additional research should be performed to validate
these promising results on a larger cohort of patients and using different
classification strategies. Advances in knowledge: This is the first study
assessing the role of an automatic CAD system in predicting the pathological
response to NAC before treatment. Fully automatic methods represent the backbone
of standardized analysis and may help in timely managing patients candidate to
NAC.
PMID- 28707547
TI - 'We need a safe, walkable way to connect our sisters and brothers': a qualitative
study of opportunities and challenges for neighborhood-based physical activity
among residents of low-income African-American communities.
AB - OBJECTIVE: The purpose of this study was to explore perceptions of the benefits
of and influencing factors for neighborhood-based physical activity (PA), and
elicit suggestions for increasing neighborhood-based PA among primarily Black
residents living in lower income neighborhoods. DESIGN: Eight focus groups were
conducted in low-income, predominantly Black neighborhoods (n = 8) in Greenville,
SC during Spring 2014. Using a semi-structured focus group guide with open-ended
questions, residents were asked to describe benefits of PA, neighborhood factors
associated with PA, and ways to increase PA within their neighborhoods. Trained
research assistants transcribed audio recordings verbatim. Using grounded theory
and an ecological perspective, emergent coding was employed to generate initial
categories with open and axial coding used to achieve consensus on themes.
RESULTS: Primarily Black (95%), female (72%), and older (M = 61.5 years)
residents (N = 76) participated in the study. Seven themes were identified across
the three main focus group topics: physical and mental health benefits of
neighborhood PA, safety/hazards and social factors as influencing neighborhood
PA, and improving safety, structural opportunities, and programing support to
improve neighborhood PA. Most participants reported walking within their
communities, despite describing several community-level barriers (e.g. drugs,
safety). Residents desired structured neighborhood-based opportunities for
increasing PA, including walking tracks and walking groups, and reported social
benefits to being active, including increased awareness within the community and
trust. Participants conveyed that walking strengthened the social environment of
their community as well as the health of residents. CONCLUSION: Few studies of
contextual factors and PA have focused on African-American, low-income
neighborhoods. Despite diverse environmental constraints, residents reported
walking within their communities as part of a healthy lifestyle. Social
ecological interventions tailored to promote PA and reduce health disparities
among residents of low-income communities should highlight neighborhood-based
opportunities for PA, focusing on personal and collective social benefits of
neighborhood walking.
PMID- 28707548
TI - Geographical assignment of hospitalists in an urban teaching hospital:
feasibility and impact on efficiency and provider satisfaction.
AB - OBJECTIVE: To evaluate whether implementation of a geographic model of assigning
hospitalists is feasible and sustainable in a large hospitalist program and
assess its impact on provider satisfaction, perceived efficiency and patient
outcomes. METHODS: Pre (3 months) - post (12 months) intervention study conducted
from June 2014 through September 2015 at a tertiary care medical center with a
large hospitalist program caring for patients scattered in 4 buildings and 16
floors. Hospitalists were assigned to a particular nursing unit (geographic
assignment) with a goal of having over 80% of their assigned patients located on
their assigned unit. Satisfaction and perceived efficiency were assessed through
a survey administered before and after the intervention. RESULTS: Geographic
assignment percentage increased from an average of 60% in the pre-intervention
period to 93% post-intervention. The number of hospitalists covering a 32 bed
unit decreased from 8-10 pre to 2-3 post-intervention. A majority of physicians
(87%) thought that geography had a positive impact on the overall quality of
care. Respondents reported that they felt that geography increased time spent
with patient/caregivers to discuss plan of care (p < 0.001); improved
communication with nurses (p = 0.0009); and increased sense of teamwork with
nurses/case managers (p < 0.001). Mean length of stay (4.54 vs 4.62 days), 30-day
readmission rates (16.0% vs 16.6%) and patient satisfaction (79.9 vs 77.3) did
not change significantly between the pre- and post-implementation period. The
discharge before noon rate improved slightly (47.5% - 54.1%). CONCLUSIONS:
Implementation of a unit-based model in a large hospitalist program is feasible
and sustainable with appropriate planning and support. The geographical model of
care increased provider satisfaction and perceived efficiency; it also
facilitated the implementation of other key interventions such as
interdisciplinary rounds.
PMID- 28707549
TI - Efficacy, Safety, and Timing of 5% Sodium Chloride Compared With 23.4% Sodium
Chloride for Osmotic Therapy.
AB - BACKGROUND: Bolus doses of 23.4% sodium chloride (NaCl) are commonly used for the
treatment of intracranial hypertension; however, delays in administration may
occur in patients without central intravenous access. At our institution,
equiosmolar bolus doses of 5% NaCl have emerged as potential alternatives to
23.4% NaCl because they may be safely administered through peripheral lines.
OBJECTIVES: We sought to assess the efficacy in reducing intracranial pressure
(ICP), time to administration, and safety of 5% NaCl as compared with 23.4% NaCl
for the treatment of intracranial hypertension. METHODS: Patients admitted from
July 2012 to June 2014 who received boluses of 5% NaCl or 23.4% NaCl for a
sustained ICP >20 mm Hg were included. Data collected included measurements of
ICP, time to administration, and adverse events. RESULTS: A total of 44 patients
were identified; 11 received 5% NaCl, and 33 received 23.4% NaCl. The median
percentage reductions in ICP at 30, 60, and 120 minutes in patients who received
5% versus 23.4% NaCl were 34% versus 26% ( P = 0.850), 48% versus 40% ( P =
0.700), and 46% versus 30% ( P = 0.064), respectively. The median time to
administration was shorter in the 5% NaCl group (7 vs 11 minutes, P = 0.364).
Both groups had a 27% rate of adverse events and no infusion site reactions.
CONCLUSIONS: These data suggest that 5% NaCl may be as effective as 23.4% NaCl at
lowering ICP if given at equiosmolar doses, has a shorter time to administration,
and has no difference in the prevalence of adverse events.
PMID- 28707550
TI - Rising Cost of Anticancer Medications in the United States.
AB - With more than 1.6 million new cases of cancer occurring each year, anticancer
medications are in high demand. Escalating prescription drug prices have become a
significant concern. Anticancer medications are among the most expensive
prescription medications, many of them exceeding $100 000 a year. The survival
benefits of certain newer anticancer medications may be a few months more than
that from the existing treatment but at a much higher price tag. Drug cost may
play a substantial role in making treatment choices. Multiple factors leading to
high prices and some potential solutions to lower them have been highlighted.
PMID- 28707551
TI - Vasopressin Dosing for Septic Shock.
PMID- 28707552
TI - Success Stories: Overcoming Barriers to Research in Southern and Eastern African
Countries.
AB - There is an ever-growing need for clinically focused, culturally relevant
research on which nurses can base their practice. However, there may not be a
concurrent rise in efforts to strengthen infrastructure needed to promote
research in developing and low-income countries. In such cases, nurse researchers
must find innovative ways to address and overcome barriers to research. This
article presents five exemplars of nurses conducting high-quality nursing
research in resource-poor settings in southern and eastern Africa. Furthermore,
it suggests strategies to address these barriers, such as piggybacking on larger
studies, interdisciplinary collaboration, and partnership with influential
stakeholders. These tactics may be used to increase research productivity
elsewhere.
PMID- 28707553
TI - Ziram inhibits rat neurosteroidogenic 5alpha-reductase 1 and 3alpha
hydroxysteroid dehydrogenase.
AB - The neurotoxicity of ziram is largely unknown. In this study, we investigated the
direct inhibitions of ziram on rat neurosteroid synthetic and metabolizing
enzymes, 5alpha-reductase 1 (SRD5A1), 3alpha-hydroxysteroid dehydrogenase
(AKR1C14), and retinol dehydrogenase 2 (RDH2). Rat SRD5A1, AKR1C14, and RDH2 were
cloned and transiently expressed in COS1 cells, and the effects of ziram on these
enzymes were measured. Ziram inhibited rat SRD5A1 and AKR1C14 with IC50 values of
1.556 +/- 0.078 and 1.017 +/- 0.072 MUM, respectively, when 1000 nM steroid
substrates were used. Ziram weakly inhibited RDH2 at 100 MUM, when androstanediol
(1000 nM) was used. Ziram competitively inhibited SRD5A1 and non-competitively
inhibited AKR1C14 when steroid substrates were used. Docking study showed that
ziram bound to NADPH-binding pocket of AKR1C14. In conclusion, our results
demonstrated that ziram inhibited SRD5A1 and AKR1C14 activities, thus possibly
interfering with neurosteroid production in rats.
PMID- 28707554
TI - A Battle of Words: "Dignity" and "Peace" in the Writings of Elisabeth Kubler
Ross.
AB - This article analyzes the writings of Elisabeth Kubler-Ross through the
discursive lens of the phrase "dying with dignity." For her, the phrase meant
allowing someone to die comfortably his/her own death. This phrase has to be
understood in relationship with the final "stage of acceptance" of her model.
Describing this key part of her well-known scientific output, she often used, in
the early 1970s, the phrase "dying in peace and dignity." An evaluation of the
evidence suggests that because the concept of dignity was co-opted by the pro
euthanasia movement during this decade, the language of dignity was little by
little abandoned by her. In later years, only "peace" survived from her favorite
expression. Although this concept of peace remains present to the end in all
Kubler-Ross writings, the pro-euthanasia movement has also started to speak the
language of peace.
PMID- 28707555
TI - Long-term effects of silver nanoparticles in caco-2 cells.
AB - The high success of silver nanoparticles (AgNPs), mainly associated with their
proved antimicrobial properties, has led to an increasing spread in our close
environment. Although many studies have been carried out to detect potential
toxicity of AgNPs, most of them have been developed under unrealistic exposure
conditions. In terms of human risk, the evaluation of long-term exposures to
subtoxic doses of NPs remains a challenge. Here, we have determined different
transformation-related end points under a scenario of 6 weeks long-term exposure
to low noncytotoxic AgNPs concentrations (0.5 and 1 MUg/mL) in Caco-2 cells. A
significant uptake of AgNPs was demonstrated by using confocal microscopy showing
a high presence of AgNPs in both the cytoplasm and the nucleus. As for the
assayed parameters of cell transformation such as ability to growth without
requiring adherence to a surface (soft-agar assay), the secretion of
extracellular matrix metalloproteinase to the medium (zymography), migration
capacity and ability of the secretome of exposed cells to promote tumor growth,
significant effects were detected in all cases, with the exception of the
extracellular matrix metalloproteinases (MMP2 and MMP9) secretion. Our results
point out the potential carcinogenic risk associated with AgNPs exposure under
long-term exposure conditions, as well as the importance of using realistic
exposure scenarios to test nanomaterials.
PMID- 28707556
TI - Informed consent and informed decision in maternal fetal neonatal medicine: do
they go hand in hand?
PMID- 28707557
TI - The cheek of a cheater: Effects of posing the left and right hemiface on the
perception of trustworthiness.
AB - Our cognitive mechanisms are designed to detect cheaters in social exchanges.
However, cheater detection can be thwarted by a posed smile, which cheaters
display with greater emotional intensity than cooperators. The present study
investigated the role of hemifacial asymmetries in the perception of
trustworthiness using face photographs with left and right cheek poses.
Participants (N = 170) observed face photographs of cheaters and cooperators in
an economic game. In the photographs, models expressed happiness or anger and
turned slightly to the left or right to show their left or right cheeks to the
camera. When the models expressed anger on their faces, cheaters showing the
right cheek were rated as less trustworthy than cooperators (irrespective of
cheeks shown) and cheaters showing the left cheek. When the models expressed
happiness, trustworthiness ratings increased and did not differ between cheaters
and cooperators, and no substantial asymmetries were observed. These patterns
were replicated even when the face photographs were mirror-reversed. These
results suggest that a cheater's fake smile conceals an uncooperative attitude
that is displayed in the right hemiface, ultimately disguising cheater detection.
PMID- 28707558
TI - Effect of unconjugated hyperbilirubinemia on neonatal autonomic functions:
evaluation by heart rate variability.
AB - BACKGROUND: Serum bilirubin levels beyond the physiological limits, may lead to
alterations in autonomic regulation in a newborn infant. Heart rate variability
(HRV), is a noninvasive and quantitative marker of the activity of the autonomic
nervous system (ANS). To date, few studies have demonstrated the undesirable
effects of severe unconjugated hyperbilirubinemia (UHB) on autonomic functions,
and only one study has used HRV as a marker of the autonomic activity. However,
the relationship between altered cardiac autonomic functions and UHB by using the
HRV derived from 24-hour Holter electrocardiography (ECG) recording has not been
investigated previously. OBJECTIVE: We aimed to assess whether a relationship
exists between severe UHB and cardiac autonomic dysfunction by evaluating HRV via
24-hour Holter ECG recording. METHODS: This single-center, prospective, case
control study was conducted on 50 full-term newborn infants with severe UHB
requiring phototherapy and 50 healthy infants as controls. HRV assessment was
performed by using 24-hour Holter ECG recording. RESULTS: There was no
significant difference in terms of mean average heart rate, mean maximum heart
rate and mean RR duration between the groups. However, mean minimum heart rate
was significantly lower in the study group. When 24-hour time and frequency
domain parameters were compared, time and frequency domain parameters rMSDD as
well as high frequency (HF), which represent parasymphathetic activity, were
significantly higher in the study group. Furthermore, low frequency to high
frequency (LF/HF) ratio, that serves as an indicator of sympathovagal balance,
was significantly lower in the study group. CONCLUSION: Severe UHB may cause
cardiac autonomic dysfunction in favor of parasympathetic predominance in
jaundiced neonates.
PMID- 28707559
TI - Viscoelastic properties of mitral valve leaflets: An analysis of regional
variation and frequency-dependency.
AB - The aim of this study was to determine the regional variation in viscoelastic
properties of mitral valve leaflets over a range of physiological and patho
physiological frequencies. This included comparisons to be made between anterior
and posterior leaflets, anterior leaflet clear and rough zones, and radial and
circumferential leaflet orientation. Dynamic mechanical analysis was used to
determine frequency-dependent viscoelastic properties. The valve leaflets were
dissected from eight porcine hearts. The leaflets were loaded under a sinusoidal
tensile displacement, with a mean dynamic peak to trough strain of 11%, applied
to all leaflet samples at nine different frequencies, ranging from 0.5 to 10 Hz.
The anterior leaflet has higher storage and loss stiffness than the posterior
leaflet. The storage stiffness of circumferential tissue is greater than that of
radially oriented valve tissue (2.0 +/- 1.6 N/mm cf. 1.7 +/- 0.9 N/mm; p < 0.05);
however, the loss stiffness is greater for radial tissue (0.15 +/- 0.07 cf. 0.14
+/- 0.09 N/mm; p < 0.05). Likewise, the storage stiffness of the anterior leaflet
clear zone is greater than that of the rough zone (2.4 +/- 1.6 cf. 2.1 +/- 1.2; p
< 0.05), but the loss stiffness is greater for the rough zone (0.17 +/- 0.09 N/mm
cf. 0.14 +/- 0.08 N/mm; p < 0.05). In conclusion, the viscoelastic properties of
porcine mitral valve leaflets have regional variations, with dynamic stiffness
being dependent on circumferential or radial orientation and on location at a
clear or rough zones.
PMID- 28707560
TI - The association of between assisted reproduction technology and
malpresentation/induction of labor: a meta-analysis.
AB - BACKGROUND: Some epidemiological studies have investigated that assisted
reproduction technology (ART) can increase the risk of malpresentation and
induction of labor. To date, no meta-analysis has been performed for assessing
the relationship between ART and malpresention/induction of labor. This meta
analysis was conducted to assess the association between ART and
malpresention/induction of labor. METHODS: A systematic search was carried out in
major databases PubMed, Web of Science, and Scopus to May 2017. The heterogeneity
across studies was explored by Q-test and I2 statistic. The publication bias was
assessed by Begg's and Egger's tests. The results were showed using odds ratio
(OR) estimate with its 95% confidence intervals (CI) using a random-effects
model. RESULTS: The systematic search included 2103 articles until May 2017 with
1,401,448 participants. Based on OR estimates obtained from case-control and
cohort studies, there was significant association between ART and risk of the
induction of labor/malpresentation (1.33; 95% CI: 1.23, 1.43) and (1.58; 95% CI:
1.17, 1.98), respectively. CONCLUSIONS: We showed based on reports in
epidemiological studies that ART is a risk factor for malpresentation and
induction of labor.
PMID- 28707561
TI - Profiling the physical load on riders of top-level motorcycle circuit racing.
AB - Manoeuvring a motorcycle at high-speed in official competition has been shown to
expose riders to substantial and complex physiological and psychological demands,
however few studies have analysed the physical load experienced by professional
racers. This study aimed to quantify the physical stress experienced by riders
and explore relationships between performance related variables (i.e. crashes).
Performance and braking data were collected from official race reports from 2013
to 2015 of the top class of the FIM Road Racing Grand Prix World Championship.
Top-level riders are exposed to a considerable volume (175 +/- 42 brakes and 372
+/- 48 leans to corner per race) of high intensity actions (>40% of brakes
initiated at speeds higher than 260 km.h-1, and 13.2% over 300 km.h-1), where 1
out of every 4 braking actions generated inertial stresses greater than 10 m.s-2.
Furthermore, the mean speed across competitions increased over the years (from
161.7 +/- 6 km.h-1 to 164.5 +/- 6 km.h-1), however no clear relationships between
the amount of crashes and competition-related factors were found. Given the
findings it would seem that riders could benefit from strength training
specifically designed to prepare the body to counteract the repetitive inertial
stresses of racing.
PMID- 28707562
TI - Percutaneous removal of a free calcified mass from the lumen of the brachial
artery.
PMID- 28707563
TI - Studies on removal of phenol sulfonic acid-syntan in aqueous medium using
ozonation.
AB - The removal of phenol sulfonic acid-syntan (PSAS) in terms of chemical oxygen
demand (COD) was studied at different pH, ozone and initial PSAS concentrations
and the optimum condition was found to be pH 7, ozone concentration of 5.2 * 10-3
mmol/L and initial PSAS concentration of 500 mg/L. The increase in BOD5/COD ratio
confirmed the bio-treatability of ozonated PSAS effluent. The excitation-emission
matrix intensity and Fourier transmission infra-red spectroscopy confirmed the
generation of intermediate by-product during degradation of PSAS. The ozonation
of PSAS was found to obey fast regime pseudo-first-order reaction with a rate
constant of 3.7 * 10-9 mol-1 s-1. The mean oxidation state of carbon value
between +2 and +3 confirmed that the ozonation of PSAS resulted in partial
mineralization.
PMID- 28707564
TI - Time trends in absolute and relative socioeconomic inequalities in leisure time
physical inactivity in northern Sweden.
AB - AIMS: The aim was to investigate the time trends in educational, occupational,
and income-related inequalities in leisure time physical inactivity in 2006,
2010, and 2014 in northern Swedish women and men. METHODS: This study was based
on data obtained from the repeated cross-sectional Health on Equal Terms survey
of 2006, 2010, and 2014. The analytical sample consisted of 20,667 (2006), 31,787
(2010), and 21,613 (2014) individuals, aged 16-84. Logistic regressions were used
to model the probability of physical inactivity given a set of explanatory
variables. Slope index of inequality (SII) and relative index of inequality (RII)
were used as summary measures of the social gradient in physical inactivity. The
linear trend in inequalities and difference between gender and years were
estimated by interaction analyses. RESULTS: The year 2010 displayed the highest
physical inactivity inequalities for all socioeconomic position indicators, but
educational and occupational inequalities decreased in 2014. However, significant
positive linear trends were found in absolute and relative income inequalities.
Moreover, women had significantly higher RII of education in physical inactivity
in 2014 and significantly higher SII and RII of income in physical inactivity in
2010, than did men in the same years. CONCLUSIONS: The recent reduction in
educational and occupational inequalities following the high inequalities around
the time of the great recession in 2010 suggests that the current policies might
be fairly effective. However, to eventually alleviate inequities in physical
inactivity, the focus of the researchers and policymakers should be directed
toward the widening trends of income inequalities in physical inactivity.
PMID- 28707565
TI - Neoliberalism and the recommodification of health inequalities: A case study of
the Swedish welfare state 1980 to 2011.
AB - AIMS: This paper examines the effects of neoliberalism on health inequalities
through an empirical examination of the recommodification of the social
determinants of health. It uses a detailed case study of changes to three
specific welfare policy domains in Sweden: unemployment, healthcare, and
pensions. METHODS: Using time series data from the repeat cross-sectional Swedish
Living Conditions Survey for 1980-2011, it examines: (1) the effects of
reductions in the replacement rate value of unemployment benefit on inequalities
in self-reported general health between the employed and the unemployed; (2) the
effects of reductions in the replacement rate value of pensions on educational
inequalities in self-reported general health among pensioners; and (3) the
effects of the increase in user charges on inequalities in having visited a
doctor in the past 3 months by educational level. RESULTS: The results suggest
mixed effects of welfare state recommodification on health inequalities:
inequalities increased between the Swedish employed and unemployed, yet they did
not increase in the retired population, and inequalities in access to healthcare
also remained steady during the study period. CONCLUSIONS: The paper concludes
that the association between recommodification and health inequalities in Sweden
is stronger regarding unemployment benefits than pensions or healthcare, and that
this may relate to the stigmatisation of the unemployed.
PMID- 28707566
TI - Mediastinal dedifferentiated liposarcoma.
PMID- 28707567
TI - The impact of a social network based intervention on self-management behaviours
among patients with type 2 diabetes living in socioeconomically deprived
neighbourhoods: a mixed methods approach.
AB - AIMS: This paper aims to explore the effect of the social network based
intervention Powerful Together with Diabetes on diabetes self-management among
socioeconomically deprived patients. This 10-month group intervention targeting
patients and significant others aimed to improve self-management by stimulating
social support and diminishing social influences that hinder self-management.
METHODS: This intervention was evaluated in a quasi-experimental study using a
mixed methods approach. Of 131 socioeconomically deprived patients with
suboptimal glycaemic control, 69 were assigned to the intervention group and 62
to the control group (standard diabetes education). 27 qualitative in-depth
interviews with the participants and 24 with their group leaders were held to
study the subjective impact of the intervention. Further, self-management
behaviours (medication adherence, diet and physical activity) were assessed at
baseline, 10 and 16 months. Data were analysed using framework analyses and a
linear mixture model. RESULTS: Qualitative data showed that the intervention
group had a better understanding of the way self-management influences diabetes.
The intervention group showed more complex self-management behaviours, such as
planning ahead, seeking adequate food and physical activity alternatives, and
consistently taking their diabetes into consideration when making choices. In
participants with complete follow-up data, we found a significant increase in
physical activity in the intervention group (3.78 vs. 4.83 days) and no changes
in medication adherence and diet. CONCLUSIONS: This study indicates that an
intensive support group and simultaneously involving significant others might
improve diabetes self-management behaviours among socioeconomically deprived
patients. More studies are needed to justify further implementation of the
intervention. This study is registered in the Dutch Trial Register NTR1886.
http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=1886.
PMID- 28707568
TI - Effects of Transcranial Direct Current Stimulation on Neural Networks in Young
and Older Adults
AB - Transcranial direct current stimulation (tDCS) may be a viable tool to improve
motor and cognitive function in advanced age. However, although a number of
studies have demonstrated improved cognitive performance in older adults, other
studies have failed to show restorative effects. The neural effects of beneficial
stimulation response in both age groups is lacking. In the current study, tDCS
was administered during simultaneous fMRI in 42 healthy young and older
participants. Semantic word generation and motor speech baseline tasks were used
to investigate behavioral and neural effects of uni- and bihemispheric motor
cortex tDCS in a three-way, crossover, sham tDCS controlled design. Independent
components analysis assessed differences in task-related activity between the two
age groups and tDCS effects at the network level. We also explored whether
laterality of language network organization was effected by tDCS. Behaviorally,
both active tDCS conditions significantly improved semantic word retrieval
performance in young and older adults and were comparable between groups and
stimulation conditions. Network-level tDCS effects were identified in the ventral
and dorsal anterior cingulate networks in the combined sample during semantic
fluency and motor speech tasks. In addition, a shift toward enhanced left
laterality was identified in the older adults for both active stimulation
conditions. Thus, tDCS results in common network-level modulations and behavioral
improvements for both age groups, with an additional effect of increasing left
laterality in older adults.
PMID- 28707569
TI - Imaginative Reinforcement Learning: Computational Principles and Neural
Mechanisms.
AB - Imagination enables us not only to transcend reality but also to learn about it.
In the context of reinforcement learning, an agent can rationally update its
value estimates by simulating an internal model of the environment, provided that
the model is accurate. In a series of sequential decision-making experiments, we
investigated the impact of imaginative simulation on subsequent decisions. We
found that imagination can cause people to pursue imagined paths, even when these
paths are suboptimal. This bias is systematically related to participants'
optimism about how much reward they expect to receive along imagined paths;
providing feedback strongly attenuates the effect. The imagination effect can be
captured by a reinforcement learning model that includes a bonus added onto
imagined rewards. Using fMRI, we show that a network of regions associated with
valuation is predictive of the imagination effect. These results suggest that
imagination, although a powerful tool for learning, is also susceptible to
motivational biases.
PMID- 28707570
TI - Using Event-related Potentials to Inform the Neurocognitive Processes Underlying
Knowledge Extension through Memory Integration.
AB - To build a general knowledge base, it is imperative that individuals acquire,
integrate, and further extend knowledge across experiences. For instance, in one
episode an individual may learn that George Washington was the first president.
In a separate episode they may then learn that Washington was the commander of
the Continental Army. Integration of the information in memory may then support
self-derivation of the new knowledge that the leader of the Continental Army was
also the first president. Despite a considerable amount of fMRI research aimed at
further elucidating the neuroanatomical regions supporting this ability, a
consensus has yet to be reached with regards to the precise neurocognitive
processes involved. In the present research, we capitalized on the high temporal
resolution of event-related potentials (ERPs) to inform the time course of
processes elicited during successful integration and further extension of new
factual knowledge. Adults read novel, related stem facts and were tested for self
derivation of novel integration facts while ERPs were recorded. Consistent with
current theoretical models, memory integration was first triggered by novelty
detection within 400 msec of experience of a second, related stem fact. Two
additional temporally staged encoding processes were then observed interpreted to
reflect (1) explicit meaning comprehension and (2) representation of the
integrated relation in memory. During the test for self-derivation, a single ERP
was elicited, which presumably reflected retrieval and/or recombination of
previously integrated knowledge. Together, the present research provides
important insight into the time course of neurocognitive processing associated
with the formation of a knowledge base.
PMID- 28707571
TI - How Do You See Me? The Neural Basis of Motivated Meta-perception.
AB - We cannot see the minds of others, yet people often spontaneously interpret how
they are viewed by other people (i.e., meta-perceptions) and often in a self
flattering manner. Very little is known about the neural associations of meta
perceptions, but a likely candidate is the ventromedial pFC (VMPFC). VMPFC has
been associated with both self- and other-perception as well as motivated self
perception. Does this function extend to meta-perceptions? The current study
examined neural activity while participants made meta-perceptive interpretations
in various social scenarios. A drift-diffusion model was used to test whether the
VMPFC is associated with two processes involved in interpreting meta-perceptions
in a self-flattering manner: the extent to which the interpretation process
involves the preferential accumulation of evidence in favor of a self-flattering
interpretation versus the extent to which the interpretation process begins with
an expectation that favors a self-flattering outcome. Increased VMPFC activity
was associated with the extent to which people preferentially accumulate
information when interpreting meta-perceptions under ambiguous conditions and
marginally associated with self-flattering meta-perceptions. Together, the
present findings illuminate the neural underpinnings of a social cognitive
process that has received little attention to date: how we make meaning of
others' minds when we think those minds are pointed at us.
PMID- 28707572
TI - Erratum.
PMID- 28707573
TI - Synthesis, Radiosynthesis and Metabolism of 131I-Y-c(CGRRAGGSC).
AB - BACKGROUND: The formation of the complex interleukin-11(IL-11) and IL-11 receptor
(IL-11R) is closely related with tumor progression. Binding of IL-11 to the IL-11
receptor alpha-chain (IL-11Ralpha) has been suggested as a target for human
cancer. The cyclic peptide c(CGRRAGGSC) is a mimic of IL-11. OBJECTIVE: To
explore 131I-Y-c(CGRRAGGSC) synthesis and radiosynthesis, and metabolism in SKOV3
tumorbearing mice. METHOD: In this study, 131I labeled c(CGRRAGGSC) was designed
and characterized. For radiolabeling, tyrosine was used as a linker to connect
c(CGRRAGGSC) and 131I. Balb/c nude mice bearing SKOV3 human ovarian carcinoma
were used for in vivo studies. Uptake of 131I-cyclic nonapeptide by the tumor was
visualized by single photon emission computerized tomography (SPECT). RESULTS:
The entire labeling process, which took 15 min by chloramine-T method, resulted
in a high labeling yield (93.03+/-6.78%), and high radiochemical purity (RCP)
(>95%). SPECT imaging showed that accumulation of the probe in the tumor was
close to background levels. In addition, biodistribution studies showed that the
accumulation of 131I-Y-c(CGRRAGGSC) in normal mice was similar to that of Na131I.
CONCLUSION: Tyrosine is a suitable chelating agent for the use of radioiodine
labeling, however the bioactivity of the conjugate needs further investigation.
PMID- 28707574
TI - Recent Progress of Nano-drug Delivery System for Liver Cancer Treatment.
AB - Liver cancer is one of serious diseases which threaten human life and health.
Studies on the treatment of liver cancer have attracted widespread attention.
Application of nano-drug delivery system (NDDS) can not only improve selective
drug delivery to liver tissue and improve the bioavailability of drug, but also
can reduce the side effects of drugs when it is specially modified in the
respects of structure modification or specific target molecules decoration. This
review will address the latest development of liver-targeted drug delivery
system.
PMID- 28707576
TI - New Strategies for the Prevention and Treatment of Systemic and Local Bone Loss;
from Pathophysiology to Clinical Application.
AB - Bone loss is the result of a negative unbalance between bone formation ad bone
resorption. In the last years, the studies on the Wnt canonical pathway have
highlighted its crucial role in bone balance through its influence on the
activity and maturation of the osteoblast line and in the Receptor Activator of
Nuclear Factor kappa B (RANK) - RANK ligand (RANKL)/Osteoprotegerin (OPG) system.
These mechanisms are involved not only in the pathological processes inducing not
only systemic bone loss (i.e. Postmenopausal osteoporosis, glucocorticoid-
induced osteoporosis, etc.), but also at a local level, as happens in Rheumatoid
Arthritis (RA). Recently, several new drugs for the treatment of bone loss have
been approved, while some others are still under development. The most promising
new drugs in the treatment of osteoporosis include the antibody that neutralizes
RANKL (denosumab, DMAb), monoclonal antibodies against sclerostin and parathyroid
hormone-related protein analogue. Other new strategies for the prevention and
treatment of bone loss include calcilytics, cathepsin K inhibitor or the
combination or the sequential use of the current drugs. New insights concerning
the treatment of the local bone loss in RA and in Complex Regional Pain Syndrome
type I are also provided in this review.
PMID- 28707575
TI - Bayes Syndrome and Imaging Techniques.
AB - BACKGROUND: Interatrial block (IAB) is due to disruption in the Bachmann region
(BR). According to whether interatrial electrical conduction is delayed or
completely blocked through the BR, it can be classified as IAB of first, second
or third degree. On the surface electrocardiogram, a P wave >= 120 ms (partial
IAB) is observed or associated to the prolongation of the P wave with a biphasic
(positive / negative) morphology in the inferior leads (advanced IAB). Bayes
syndrome is defined as an advanced IAB associated with atrial arrhythmia, more
specifically atrial fibrillation. Objective and Conclusion: The purpose of this
review is to describe the latest evidence about an entity considered an
anatomical and electrical substrate with its own name, which may be a predictor
of supraventricular arrhythmia and cardioembolic cerebrovascular accidents, as
well as the role of new imaging techniques, such as echocardiographic strain and
cardiac magnetic resonance imaging, in characterizing atrial alterations
associated with this syndrome and generally in the study of anatomy and atrial
function.
PMID- 28707577
TI - High-Performance Enzyme-Free Glucose Sensor with Co-Cu Nanorod Arrays on Si
Substrates.
AB - BACKGROUND: Glucose sensors have been extensively researched in patent studies
and manufactured a tool for clinical diabetes diagnosis. Although some kinds of
electrochemical enzymatic glucose sensors have been commercially successful,
there is still room for improvement, in selectivity and reliability of these
sensors. Because of the intrinsic disadvantages of enzymes, such as high
fabrication cost and poor stability, non-enzymatic glucose sensors have recently
been promoted as next generation diagnostic tool due to their relatively low
cost, high stability, prompt response, and accuracy. OBJECTIVE: In this research,
a novel free standing and binder free non-enzymatic electrochemical sensor was
manufactured using in situ grown copper (Cu) and cobalt (Co) on a silicon (Si)
substrate. METHODS: Scanning High-Energy Electron Diffraction (SHEED) and Edward
deposition methods were used to synthesise the sensors. RESULTS: Morphological
observations showed that Cu and Co homogeneously formed nanorod-like shapes over
the Si substrate. The elemental composition and structure of the prepared sensors
were identified by Reflection High-Energy Electron Diffraction (RHEED). In terms
of electrochemical properties, for the enzyme-free glucose sensor, voltammograms
showed that the peak currents increased when the glucose solution was injected
into the electrolytic cell. The electrical relation of voltage versus current was
linear, as shown in the experimental data. Another effective parameter changed
the magnetic field; and the linear behaviour of the electrical resistance of Co
remained unaltered. CONCLUSION: In the optimum annealing temperature, where the
magnetic field increased, the properties of the samples remained constant. In
other words, in the selected annealing temperature, resistance and stability of
the layers increased in a significant manner.
PMID- 28707578
TI - Acute Otitis Media in Children.
AB - BACKGROUND: Acute otitis media is a common childhood infection. Prompt diagnosis
and appropriate treatment are very important. OBJECTIVE: To review in depth the
epidemiology, pathophysiology, clinical manifestations, diagnosis, complications
and particularly treatment of acute otitis media in children. METHODS: A PubMed
search was completed in Clinical Queries using the key term "acute otitis media".
Patents were searched using the key term "acute otitis media" from
www.google.com/patents, http://espacenet.com, and www.freepatentsonline.com.
RESULTS: Acute otitis media affects over 80% of children before their third
birthday and 30 to 45% of these children have suffered two or more episodes.
Streptococcus pneumoniae, nontypable Haemophilus influenzae, and Moraxella
catarrhalis are the most frequently isolated middle-ear pathogens. The diagnosis
is based on acute onset of symptoms such as otalgia and fever, middle ear
inflammation such as erythema of the tympanic membrane, and middle ear effusion.
The choice of treatment method depends on the age of the child, laterality, and
the severity of the disease. Recent patents related to the management of acute
otitis media are also retrieved and discussed. CONCLUSION: Antimicrobial
treatment is recommended for all children less than two years of age, as well as
in children >= two years of age who have a temperature >= 39oC; are toxic
looking; have otalgia > 48 hours; have bilateral otitis media or otorrhea; have
craniofacial abnormalities; are immunocompromised; or have uncertain access to
follow-up. Amoxicillin is the drug of choice. Observation without antibiotic is
an option in immunocompetent children >= two years of age who have an acute
uncomplicated otitis media and non-severe illness if appropriate follow-up can be
arranged.
PMID- 28707579
TI - The Involvement of ERCC2/XPD and ERCC6/CSB Wild Type Alleles in Protection
Against Aging and Cancer.
AB - BACKGROUND: DNA helicases maintain genome stability, and their deficiency is
associated with disorders resembling premature aging as well as contributes to
carcinogenesis. Their functions are determined by the respective genes encoding
nucleotide excision repair initiating proteins, e.g. XPD and CSB. OBJECTIVE: The
present study aimed to investigate the influence of genetic variations in
ERCC2/XPD (rs1799793, rs13181) and ERCC6/CSB (rs2228526, rs2228528) loci on
lifespan and developing age-related bladder cancer focusing on homozygous wild
type alleles. METHOD: The allelic variants were identified in 354 clinically
healthy controls and 418 bladder cancer patients using the PCR-RFLP method.
RESULTS: The age-depended increase in frequencies of homozygous carriers of wild
type XPD 312Asp and XPD 751Lys alleles was observed among controls, especially
among subjects over 80 years (r = 0.67, p = 0.012). The statistically significant
correlation was also found between the frequency of homozygous wild type alleles
at all tested loci and age in healthy population over 60 years (r = 0.35, p =
0.046) suggesting the relationship between lifespan and longevity, on one hand,
and normal functioning of these genes and their products, on the other hand.
Homozygous carriers of wild type alleles were less susceptible to bladder cancer,
tumor invasion, increase in grade of malignancy and recurrence, but their effects
were specific with respect to clinicopathological and lifestyle characteristics.
CONCLUSION: Homozygous wild type alleles encoding XPD and CSB proteins with
optimal properties were shown to affect human lifespan, risk of developing
bladder cancer, its progression and recurrence under certain conditions.
PMID- 28707580
TI - Doxorubicin-Loaded Micelle Targeting MUC1: A Potential Therapeutic for MUC1
Triple Negative Breast Cancer Treatment.
AB - BACKGROUND: Triple negative breast cancer (TNBC) is an aggressive disease
associated with poor prognosis and lack of validated targeted therapy. Thus
chemotherapy is a main adjuvant treatment for TNBC patients, but it associates
with severe toxicities. For a better treatment outcome, we developed an
alternative therapeutic, doxorubicin (DOX)-loaded micelles targeting human mucin1
protein (MUC1) that is less toxic, more effective and targeted to TNBC. METHODS:
From many candidate peptides, QNDRHPR-GGGSK (QND) and HSQLPQV-GGGSK (HSQ) were
identified computationally, synthesized and purified using solid phase peptide
synthesis and semipreparative HPLC. The peptides showed significant high binding
to MUC1 expressing cells using a fluorescent microscope. The peptides were then
conjugated on pegylated octadecyl lithocholate copolymer. DOX-encapsulated
micelles were formed through self-assembly. MUC1-targeted micelles were
characterized using dynamic light scattering (DLS) and Transmission Electron
Microscopy (TEM). Drug entrapment efficiency was examined using a microplate
reader. Cytotoxicity, binding, and uptake were also investigated. RESULTS: Two
types of DOX-loaded micelles with different targeting peptides, QND or HSQ, were
developed. DOX-loaded micelles were spherical in shape with average particle size
around 300-320 nm. Drug entrapment efficiency of untargeted and targeted DOX
micelles was about 71-93%. Targeted QND-DOX and HSQ-DOX micelles exhibited
significantly higher cytotoxicity compared to free DOX and untargeted DOX
micelles on BT549-Luc cells. In addition, significantly greater binding and
uptake were observed for QND-DOX and HSQ-DOX micelles on BT549-Luc and T47D
cells. CONCLUSION: Taken together, these results suggested that QND-DOX and HSQ
DOX micelles have a potential application in the treatment of TNBC-expressing
MUC1.
PMID- 28707581
TI - Synthesis and Evaluation of Novel Diazaspiro Hydantoins as Potential
Anticonvulsants.
AB - BACKGROUND: Epilepsy, one of the most frequent neurological afflictions in man
characterized by excessive temporary neuronal discharges resulting in
uncontrolled convulsion, requires special medical attention. Though several new
anticonvulsants are introduced, some types of seizures are still not adequately
treated with current therapy. Toxicity, intolerance, and lack of efficacy for
certain types of seizure are some of the limitations of the current medications.
METHODS: Maximal electroshock (MES) seizure model was used in the present study
to evaluate the anticonvulsant activity of the drugs. Seizures were induced in
ten weeks old male Wistar rats (200-220 g) by delivering electro shock of 150 mA
for 0.2 sec by means of a convulsiometer through a pair of ear clip electrodes.
The test compounds (1-10, 100 mg/kg) were administered by oral route 30 mins
before the maximal electroshock seizure test by suspending in
carboxymethylcellulose (1%). The animals were observed closely for 2 mins. The
percentage of inhibition of seizure relative to control was recorded and
calculated. Phenytoin (100 mg/kg, p.o) was used as a standard drug. The data was
analysed by using one way ANOVA followed by dunnett's test. RESULTS: In our
present series of compounds the active compounds possess all the requirements
essential for anticonvulsant activity as proposed by Dimmock and others. In this
study, it reveals that, compounds showing anticonvulsant activity with more
lipophilic N-substitution group are more active than hydrophobic substitution in
the hydantoin ring. The rapid onset of action is believed to be due to the
substitution of more lipophilic propyl group in the N-substitution in the
hydantoin moiety. Evidently, this distal hydrophobic centre alters the
bioavailability of the molecules. CONCLUSION: The results are encouraging and
show that, the hydantoins are more potential molecules for the treatment of
anticonvulsant. Anticonvulsants have greatly improved the lives of people with
epilepsy. Approximately 70% of patients can achieve complete freedom from
seizures with appropriate treatment. Lipophilicity appears to govern the MES
activity. If there is lipophilic moiety, then MES activity is favoured. All the
compounds have shown promising and significant protective effect on maximal
electroshock induced seizures when compared to vehicle treated control rats.
PMID- 28707582
TI - Modulation of microRNAs in Tooth Root and Periodontal Tissue Development.
AB - BACKGROUND: Tooth root development begins after the completion of tooth crown
development. Both the tooth root and crown undergo a series of interactions
between the epithelium and adjacent mesenchymal cells. Although many studies have
evaluated tooth crown formation, little is known about the regulatory mechanisms
of tooth root development. MicroRNAs (miRNAs) are small noncoding RNAs that
regulate protein expression through post-transcriptional mechanisms and
participate in a broad range of biological processes, from development to
tumorigenesis. The functional importance of miRNAs on the development of tooth
root and periodontal tissues has been suggested in many studies. OBJECTIVE: To
summarize the functions of miRNAs on tooth root and periodontal tissue
development. RESULTS: MicroRNAs are important to root odontogenesis, Hertwig's
epithelial root sheath and periodontal tissue development, and have functions in
stem cells from dental or periodontal tissues. CONCLUSION: The modulation of
miRNAs in tooth root and periodontal tissue development is fine tuning.
PMID- 28707583
TI - Cannabis: An Overview of its Adverse Acute and Chronic Effects and its
Implications.
AB - In many communities, cannabis is perceived as a low-risk drug, leading to
political lobbying to decriminalise its use. Acute and chronic cannabis use has
been shown to be harmful to several aspects of psychological and physical health,
such as mood states, psychiatric outcomes, neurocognition, driving and general
health. Furthermore, cannabis is highly addictive, and the adverse effects of
withdrawal can lead to regular use. These in turn have adverse implications for
public safety and health expenditure. Although the cannabinoid cannabidiol (CBD)
has been shown to have positive health outcomes with its antioxidant,
anticonvulsant, anti-inflammatory and neuroprotective properties, high-potency
cannabis is particularly damaging due to its high tetrahydrocannabinol (THC), low
CDB concentration. It is this high-potency substance that is readily available
recreationally. While pharmaceutical initiatives continue to investigate the
medical benefits of CDB, "medicinal cannabis" still contains damaging levels of
THC. Altogether, we argue there is insufficient evidence to support the safety of
cannabis and its subsequent legalisation for recreational use. Furthermore, its
use for medicinal purposes should be done with care. We argue that the public
conversation for the legalisation of cannabis must include scientific evidence
for its adverse effects.
PMID- 28707584
TI - A Review of Recent Advancements in Anti-tubercular Molecular Hybrids.
AB - Tuberculosis (TB) accounts for millions of deaths worldwide every year. Diverse
survival strategies adopted by Mycobacterium tuberculosis (Mtb) have
substantially hindered the existing anti-TB regimen thereby leading to multidrug
resistant (MDR) and extremely drug-resistant (XDR) strains of TB. The steady
decrease in current antibiotics' efficacy against these adversities is an
indicator that their adequate replenishment in future is almost impossible,
placing society on the precipice of a catastrophe. Over the past many years,
researchers have been continuously generating new armamentarium of anti- TB drugs
by tailoring the properties of available drugs or designing completely new
agents. One of these emerging and successful synthetic techniques is molecular
hybridization (MH) that involves the integration of different pharmacophoric
subunits to form a new prototype with the ability to be recognized by multiple
receptors. In most cases, the resultant conjugates have been reported to exhibit
superior biological activity profiles relative to their parent molecules which is
attributed to their different or dual modes of action. Accordingly, several new
effective anti-TB scaffolds have been synthesized using this approach, and are
well cited in literature. In this review, we provide a summarized account of the
chemical strategies optimistically focused to develop new molecular assemblies
for TB via MH approaches. Additionally, the structure activity relationships
revealed from different biological assays is systematically discussed.
PMID- 28707585
TI - Migraine, Neurogenic Inflammation, Drug Development - Pharmacochemical Aspects.
AB - BACKGROUND: Migraine is a primary headache disorder. Despite numerous studies
conducted with the aim to understand the pathophysiology of migraine, several
aspects are still unclear. The trigeminovascular system plays a key role.
Neurogenic inflammation is presumed to be an important factor in migraine
pathophysiology, mediated by the activation of primary neurons, leading to the
release of various pro-inflammatory neuropeptides and neurotransmitters such as
Calcitonin Gene-Related Peptide (CGRP), substance P (SP), and vasoactive
intestinal peptide (VIP). Nitric oxide (NO), Pituitary adenylate cyclase
activating polypeptide (PACAP) and Glutamate (Glu) also play an important role in
the modulation of inflammatory mechanisms. OBJECTIVE: To review the literature
focusing on novel therapeutic targets in migraine, related to neurogenic
inflammation. METHOD: A systematic literature search in the database of PUBMED
was conducted regarding therapeutic strategies in migraine, focusing on
substances and cytokines released during neurogenic inflammation, published until
January 2017. RESULTS: Ongoing phase III clinical studies with monoclonal
antibodies against CGRP and CGRP receptors offer promising novel aspects for
migraine treatment. Preclinical and clinical studies targeting SP and nitric
oxide synthase (NOS) were all terminated with no significant results compared to
placebo. New promising therapeutic goal could be PACAP and its receptor (PAC1),
and kynurenic acid (KYNA) analogues. CONCLUSION: Current migraine treatment
offers pain relief only for a small proportion of migraine patients and might not
be adequate for patients with cardiovascular comorbidity due to side effects.
Better understanding of migraine pathophysiology might, therefore, lead to novel
therapeutic lines both in migraine attack treatment and prophylaxis.
PMID- 28707586
TI - An Overview of New Possible Treatments of Alzheimer's Disease, Based on Natural
Products and Semi-Synthetic Compounds.
AB - BACKGROUND: Dementias and all related neurodegenerative diseases of the Central
Nervous System (CNS) are a current issue arousing a great deal of interest in the
international scientific community. This is due to the increasing number of
patients suffering from these diseases. These pathologies represent a serious
problem, not only concerning the quality of life of the patient, but in addition,
the enormous economic efforts that society has to do for their treatment. There
are currently a few strategies that are available in order to prevent the
progression or to mitigate symptoms of the aforementioned diseases. This
consideration is particularly true if we consider the specific pathology of
Alzheimer's Disease (AD). METHODS: We performed a literature search for peer
reviewed articles using different databases, such as PubMed or Scopus, and
exploiting different keywords and different logical operators. RESULTS: Ninety
eight papers were included in the review. Four papers give an overview of the
background of the dementias all over the world. The remaining papers are focused
on new possibilities of treatment with natural and semi-synthetic compounds for
AD. CONCLUSION: The aim of this review is to give an overview of new and
promising natural products and semi-synthetic compounds which could represent a
source of "lead compounds" for the development of new potential drugs that could
be a valid therapeutic strategy for the treatment of this pathology.
PMID- 28707587
TI - Immunotherapeutic Interleukin-6 or Interleukin-6 receptor blockade in cancer:
challenges and opportunities.
AB - Interleukin 6 (IL-6), a well-known pro-inflammatory cytokine with pleiotropic
activity is a central player in chronic inflammatory diseases including cancers.
Therefore, blockade of the IL-6 signaling pathway has become a target for the
therapy of in diverse cancers such as multicentric Castleman's disease (CD),
multiple myeloma and solid tumours including renal, prostate, lung, colorectal
and ovarian cancers. Monoclonal antibodies against IL-6 (Siltuximab) and the IL-6
receptor (IL-6R) (Tocilizumab) have emerged as potential immunotherapies, alone
or in combination with conventional chemotherapy. Human trials have demonstrated
the ability to block IL-6 activity and in multicentric CD lead to durable
clinical response and longer disease stabilisation. However, the efficacy of
these treatments is still debatable for other cancers. New generation
therapeutics in development such as Clazakizumab, Sarilumab, and soluble gp130Fc
has the additional features of improved binding affinity, better specificity with
reduced adverse effects. A deeper understanding of the immunological basis of
these agents, as well as of the challenges that are faced by immunotherapy-based
products in clinical trials, will help select the most promising anti-IL-6/IL-6R
therapies for large scale use. Concurrently, current research efforts to
personalize treatments, may help in treatment of patients that would greatly
benefit from IL-6 blocking therapies.
PMID- 28707588
TI - Targeting the Prokineticin System to Control Chronic Pain and Inflammation.
AB - Prokineticin1 and prokineticin2 belong to a new family of chemokines identified
in several species including mammals and characterized by the presence of five
disulfide bridges. These proteins signal through two G-coupled receptors
(prokineticin-receptor1 and prokineticin- receptor2) widely expressed in all
tissues and involved in a large spectrum of biological activities, including
angiogenesis, hematopoiesis, immune processes, inflammation and nociceptive
transmission. Prokineticin2 is overexpressed in inflamed tissues and has a
crucial role in neutrophil dependent inflammation and hypernociception. Following
tissue inflammation, peripheral nerve injury, cancer, bone metastasis the
expression of prokineticin2 and of the prokineticin-receptor2 is increased also
within dorsal root ganglia and spinal cord. Prokineticin receptors, highly
expressed in nociceptor endings and dorsal root ganglia, exert a tonic activation
of TRPV1 and TRPA1 contributing to peripheral sensitization. Prokineticin2
induces activation of the prokineticin receptors in the spinal dorsal horn and in
activated astrocytes contributes to central sensitization and maintains chronic
and neuropathic pain. Prokineticin2, acting on prokineticin receptors on
monocytes, macrophages and dendritic cells, induces chemotaxis and release of
inflammatory and pronociceptive cytokines. Hence, the prokineticin system
represents a novel therapeutic target in chronic pain conditions. Evaluation of
the mechanism of action of prokineticin2 and the potential effectiveness of its
inhibition is discussed.
PMID- 28707589
TI - Advances in the anticancer value of the ursolic acid through nanodelivery.
AB - Ursolic acid, a natural pentacyclic triterpenoid is commonly found in plants and
foods with promising biological and pharmacological activities. The compound has
been under the attention of researchers due to its considerable anticancer
effects through suppression of differentiation, angiogenesis, invasion, and
metastasis of tumor cells via different pathways with low toxicity.
Bioavailability of ursolic acid is poor due to poor solubility of the compound in
water. Low bioavailability and short plasma half-life of ursolic acid along with
non-specific distribution in the body are considered as impediments in the
therapeutic development of the compound. Nano-drug delivery systems may improve
the pharmacokinetic, bioavailability, and therapeutic activity of some medicines.
The present review has focused on recent developments regarding nano-drug
delivery systems of ursolic acid in cancer therapy.
PMID- 28707590
TI - Combining drug and psychological treatments for Obsessive-Compulsive Disorder:
what is the evidence, when and for whom.
AB - BACKGROUND: serotonin reuptake inhibitors (SRIs) and cognitive-behavioral
psychotherapy (CBT) are first-line treatments for obsessive-compulsive disorder
(OCD). Since response is often inadequate, in recent years researchers
investigated whether combining CBT and SRIs, either ab initio or sequentially,
results in a greater reduction of obsessive-compulsive symptoms. OBJECTIVE: the
aims of the present paper are to assess if combination treatment seems adding
benefits as compared to either monotherapy alone and if sequential strategies may
be effective in converting partial or non responders to a first-line treatment
into responders. METHOD: we reviewed available literature on pharmacological and
CBT combination and sequential treatments for adult and pediatric OCD patients
and then we conducted a separate analysis for studies concerning these two
promising strategies. Search results included open-label trials and randomized
controlled trials (RCTs). RESULTS: we identified ten controlled studies assessing
the efficacy of combination treatments ab initio versus CBT alone and six
evaluating combination strategies ab initio versus medications alone. Eleven
studies, only two of which RCTs, have been published on sequential treatments.
The combination ab initio of CBT and SRIs has not been found to be clearly
superior to either monotherapy alone in most studies conducted on this topic,
except for patients with severe depression who might benefit more from the
combination versus only CBT. A sequential administration of CBT after medications
has been found useful in promoting remission in patients who partially responded
to drugs and in promoting response in resistant patients. CONCLUSION: OCD
patients with comorbid major depression should receive medication firstly,
eventually associated with CBT; for all remaining patients there is clear
evidence from the literature of no additive benefits of combining ab initio CBT
and medication. Therefore, the routine use of a combination approach in all adult
patients affected by OCD is not supported by the literature. The available
evidence supports the effectiveness of the sequential addition of CBT to SRIs.
PMID- 28707591
TI - New-Generation, Non-SSRI Antidepressants: Therapeutic Drug Monitoring and
Pharmacological Interactions. Part 1: SNRIs, SMSs, SARIs.
AB - BACKGROUND: New-generation antidepressants (NGAs) are the latest additions to the
clinician's arsenal in the fight against depression. After the introduction of
selective serotonin reuptake inhibitors (SSRIs), a plethora of other groups
followed, identified by their main mechanisms of activity: serotonin and
norepinephrine reuptake inhibitors (SNRI); serotonin modulators and stimulators
(SMS); serotonin antagonists and reuptake inhibitors (SARI); noradrenergic and
selective serotonergic antidepressants (NaSSA); norepinephrine reuptake
inhibitors (NeRI); serotonin, norepinephrine and dopamine reuptake inhibitors
(SNDRI) or triple reuptake inhibitors (TRI); and melatonin and serotonin agonists
(MaSA). Although SSRIs are still the most widely used and well known NGAs, the
other groups are increasingly being used in the current therapeutic settings
obtaining comparable clinical results, and with tolerability and safety profiles
that can often provide significant advantages over those of SSRIs. METHODS:
Scopus and PubMed databases were searched for the most significant papers
centered on the medicinal chemistry, pharmacodynamics, pharmacokinetics and
analysis in human biological fluids of the following antidepressants:
venlafaxine, duloxetine, milnacipran, trazodone, vortioxetine, vilazodone.
RESULTS: The main characteristics of commercially available non-SSRI NGAs
(belonging to the SNRI, SARI and SMS classes) are described, focusing on the role
of analytical methods that can be applied to perform therapeutic drug monitoring
(TDM), but also including drug pharmacokinetics, metabolism and interactions.
PMID- 28707592
TI - Rational drug design of antineoplastic agents using 3D-QSAR, cheminformatic, and
virtual screening approaches.
AB - BACKGROUND: Computer-Aided Drug Design has strongly accelerated the development
of novel antineoplastic agents by helping in the hit identification,
optimization, and evaluation. RESULTS: Computational approaches such as
cheminformatic search, virtual screening, pharmacophore modeling, molecular
docking and dynamics have been developed and applied to explain the activity of
bioactive molecules, design novel agents, increase the success rate of drug
research, and decrease the total costs of drug discovery. Similarity searches and
virtual screening are used to identify molecules with an increased probability to
interact with drug targets of interest, while the other computational approaches
are applied for the design and evaluation of molecules with enhanced activity and
improved safety profile. CONCLUSION: In this review are described the main in
silico techniques used in rational drug design of antineoplastic agents and
presented optimal combinations of computational methods for design of more
efficient antineoplastic drugs.
PMID- 28707593
TI - Effects of Some Indigenous Plants of North Karnataka (India) on Cardiovascular
and Glucose Regulatory Systems in Alloxan-Induced Diabetic Rats.
AB - BACKGROUND: Kenaf (Hibiscus cannabinus Linn, Pundi), Chick pea (Cicer arietinum
Linn, Chana) and Prickly lettuce (Lactuca scariola Linn, Hattaraki) leaves are a
few of indigenous plants which are routinely consumed by the people of north
Karnataka in the diet. Studies on these plants showed some potential anti
diabetic efficacies. OBJECTIVES: To examine the effect of leaves extracts of
Hibiscus cannabinus Linn, Cicer arietinum Linn and Lactuca scariola Linn on
cardiovascular integrity, glucose homeostasis and oxygen sensing cell signaling
mechanisms in alloxan induced diabetic rats. METHOD: In vitro and in vivo tests
on glucose regulatory systems and molecular markers such as - NOS3, HIF- 1alpha
and VEGF were conducted in alloxan induced diabetic rats supplemented with all
the three plant extracts. Electrophysiological analysis (HRV, LF: HF ratio,
baroreflex sensitivity, BRS) and histopathogy of myocardial tissues and elastic
artery were evaluated in diabetic rats treated with L. scariola linn. RESULTS:
Out of these three plant extracts, Lactuca scariola Linn supplementation showed
significant beneficial effects on glucose homeostasis and oxygen sensing cell
signaling pathways in alloxaninduced diabetic rats. Furthermore, effects of sub
chronic supplementation of Lactuca scariola Linn aqueous extracts showed
significant improvement in sympatho-vagal balance in diabetic rats by increase of
Heart Rate Variability (HRV) and regaining of Baroreflex Sensitivity (BRS). These
results were also corroborated with myocardial and elastic artery histopathology
of Lactuca scariola Linn supplemented diabetic rats. CONCLUSION: These findings
indicate an adaptive pathway for glucose homeostasis, oxygen sensing cell
signaling mechanisms and cardio protective actions in alloxan - induced diabetic
rats supplemented with Lactuca scariola Linn extracts.
PMID- 28707594
TI - In Vitro Effects of Nickel on Healthy Non-Allergic Peripheral Blood Mononuclear
Cells. The Role of Red Grape Polyphenols.
AB - BACKGROUND: Nickel (Ni) is widely distributed in the environment and continuous
exposure to this metal may lead to pathological manifestations, such as the human
allergic contact dermatitis. METHODS: The in vitro effects of Ni on human healthy
non allergic peripheral blood mononuclear cells (PBMCs) in the absence or
presence of red grape polyphenols have been evaluated. In the culture
supernatants, levels of cytokines have been determined by ELISA, while nitric
oxide (NO) concentration has been evaluated by a colorimetric procedure. RESULTS:
Ni per se did not affect release of interferon-gamma, interleukin (IL)-4 and IL
10. Instead, this metal dramatically reduced production of IL-17 which was
restored by the supplementation of polyphenols. Finally, while Ni significantly
increased generation of NO, polyphenols reduced production of this compound.
CONCLUSION: Taken together, all these data may indicate a preventative role of
polyphenols against Ni exposure in non allergic to Ni individuals, also
confirming the immunomodulating role of these natural products. The interaction
Ni/polyphenols/lipopolysaccharides will also be discussed.
PMID- 28707596
TI - Pseudomonas Aeruginosa Osteomyelitis of the Pubic Bone: A Case Report.
AB - Pubic osteomyelitis is a rare disease usually results from various gynecologic
and urologic surgeries. We present a-78 year old-woman admitted to the Infectious
Department of Imam Khomeini Hospital in June 2014 with pubic osteomyelitis caused
by pseudomonas aeruginosa followed by hysterectomy.
PMID- 28707595
TI - Functional Roles of the Ca2+-activated K+ Channel, KCa3.1, in Brain Tumors.
AB - BACKGROUND: Glioblastoma is the most aggressive and deadly brain tumor, with low
disease-free period even after surgery and combined radio and chemotherapies.
Among the factors contributing to the devastating effect of this tumor in the
brain are the elevated proliferation and invasion rate, and the ability to induce
a local immunosuppressive environment. The intermediateconductance Ca2+-activated
K+ channel KCa3.1 is expressed in glioblastoma cells and in tumorinfiltrating
cells. METHODS: We first describe the researches related to the role of KCa3.1
channels in the invasion of brain tumor cells and the regulation of cell cycle.
In the second part we review the involvement of KCa3.1 channel in tumor
associated microglia cell behaviour. RESULTS: In tumor cells, the functional
expression of KCa3.1 channels is important to substain cell invasion and
proliferation. In tumor infiltrating cells, KCa3.1 channel activity is required
to regulate their activation state. Interfering with KCa3.1 activity can be an
adjuvant therapeutic approach in addition to classic chemotherapy and
radiotherapy, to counteract tumor growth and prolong patient's survival.
CONCLUSION: In this mini-review we discuss the evidence of the functional roles
of KCa3.1 channels in glioblastoma biology.
PMID- 28707597
TI - Detection of Extended-Spectrum Beta-Lactamases (ESBLs) and Antibiotic
Susceptibility Patterns in Klebsiella pneumoniae in Western, Iran.
AB - BACKGROUND: Production of Beta-Lactamase enzymes, especially extended- spectrum
Beta -Lactamases (ESBL), is a primary mechanism of resistance in these
bacteria.The purpose of this study was detection of blaTEM, blaSHV, blaCTXM,
blaCTX-M-15, blaPERand blaVEBin K. pneumoniae, isolated from clinical specimens
by the PCR method and antibiotic susceptibility patterns in these strains
isolated. MATERIALS AND METHODS: During a period from October 2015 to July 2016,
52 K. pneumoniae isolates were collected from general hospitals in the city of
Sanandaj, Iran. After identifying the strains by biochemical testing, the disc
diffusion method was used for determining antimicrobial susceptibility and
screening the ESBL-producing isolates. Detection of blaTEM, blaSHV, blaCTX-M,
blaCTX-M-15, blaPER and blaVEBESBL-producing K. pneumoniae was carried out by
PCR. RESULTS: Out of 52-collected K. pneumoniae, highest and lowest rates of
resistance related to co-trimoxazole with 67.3 % and amikacin with 30.7 %. 55.7%
identified as MDR and 69.23% were ESBL-producing K. pneumoniae.blaSHV was the
most prevalent gene in ESBL-producing K. pneumoniae. blaTEM,blaCTX-M,blaCTX-M-15
producing K. pneumoniae strains showed higher rates of drug resistant compared
with negative strains (P < 0.05). CONCLUSION: Results of this study showed that
the prevalence rate of ESBL-producing K. pneumoniae isolates is increasing in MDR
strains, which raises concerns regarding the treatment of K. pneumoniae.
Therefore, molecular research in the field of antimicrobial resistance of
bacteria is essential to prevent the spread of resistant strains.
PMID- 28707598
TI - Protein Tagging, Destruction and Infection.
AB - Cells possess protein quality control mechanisms to maintain proper cellular
homeostasis. In eukaryotes, the roles of the ubiquitination and proteasome
mediated degradation of cellular proteins is well established. Recent studies
have elucidated protein tagging mechanisms in prokaryotes, involving transfer
messenger RNA (tmRNA) and pupylation. In this review, newer insights and
bioinformatics analysis of two distinct bacterial protein tagging machineries are
discussed. The machinery for tmRNAmediated tagging is present in several
eubacterial representatives, e.g. Escherichia coli, Mycobacterium tuberculosis,
Bacillus subtilis etc., but not in two archaeal representatives, such as
Thermoplasma acidophilum and Sulfolobus solfataricus. On the other hand, the
machinery involving tagging with the prokaryotic ubiquitin-like protein (Pup) is
absent in most bacteria but is encoded in some eubacterial representatives, e.g.
Mycobacterium tuberculosis and Mycobacterium leprae. Furthermore, molecular
details on the relationship between protein tagging and enzymes involved in
protein degradation in bacteria during infection are emerging. Several pathogenic
bacteria that do not express the major ATP-dependent proteases, Lon and
Caseinolytic protease (ClpP), are avirulent. Also, some ATP-independent
peptidases, such as PepA and PepN, modulate the infection process. The roles of
bacterial proteins involved in tagging and degradation during infection are
discussed. These aspects add a new dimension to better understanding of the
peculiarities of host-pathogen interactions.
PMID- 28707599
TI - Designing of Selective gamma-Secretase Inhibitory Benzenesulfonamides through
Comparative In Vitro and In Silico Analysis.
AB - BACKGROUND: In Alzheimer's disease (AD), the gene mutations have been identified
in the amyloid precursor protein (APP), the presenilin-1 (PS1) and -2 (PS2)
genes. APP is a transmembrane protein which gets cleaved by alpha- and beta-
secretase enzymes and releases Abeta peptides which forms senile plaques in brain
tissue. It contributes for local inflammatory response, subsequent oxidative
stress, biochemical changes and neuronal death. Targeting the development of
Abeta aggregates in the senile plaques is an important strategy in the treatment
of AD. To facilitate the normal processing of APP, some of the reported
approaches are stimulation of alpha- secretase activity or the
modulation/inhibition of the beta- and gamma-secretase complex. METHODS: The
mechanism of gamma-secretase inhibition is targeted based on the QSAR and
molecular docking methods. The series based on 3-chloro-2
hydroxymethylbenzenesulfonamide was selected for in silico ligand-based modeling.
Significant correlations, between their gamma-Secretase inhibitory profile and 2D
descriptors, were obtained through multiple linear regression (MLR) computational
procedure. RESULTS: During QSAR nalysis, calculated molar refractivity (CMR) and
surface tension (ST) were found to be contributing parameters along with halogen
substituent at a particular position. Applicability analysis revealed that the
suggested models have acceptable predictability (rpred2 = 0.827). CONCLUSION: The
inferences drawn from MLR were utilized to prepare a data set of fourteen
substituted benzenesulfonamides (N1-N14). The in silico studies provides strong
impetus towards systematic application of such methods during lead identification
and optimization.
PMID- 28707600
TI - A New Potent NS5A Inhibitor in the Management of Hepatitis C Virus: Ravidasvir.
AB - BACKGROUND: Chronic hepatitis C virus (HCV) is a worldwide health problem that
can lead to liver cirrhosis, liver cell failure and numerous subsequent
complications such as hepatocellular carcinoma. Till the near past, pegylated
interferon was the standard of care therapy. However, it was associated with
suboptimal success rates and many side effects. Thereafter, direct antiviral
agents (DAA) appeared and played the key role in management of HCV. One of those
recent DAAs is ravidasvir. SUMMARY: It is a potent NS5A inhibitor that was
formerly known as PPI-668. It is produced by the cooperation of Presidio
pharmaceuticals and Pharco International pharmaceutical company. Since its first
production, it has been enrolled in different successive clinical trials. Phase 1
and 2 trials confirmed its safety and tolerability and its great efficacy in
suppressing viral loads in short periods. It has a pangenotypic activity with
favorable pharmacokinetic properties. Ravidasvir inhibits the replication of HCV
variants that develop resistance mutations for different DAA classes. Even more,
HCV variants that had reduced susceptibility to ravidasvir are completely
susceptible to other DAA. Finally, a large multicenteric registrational phase 3
clinical trial that included large percentages of difficult to treat patients
(such as cirrhotic and interferon experienced patients) has been fully
accomplished and proved great SVR12 rates. CONCLUSION: Ravidasvir is a potent new
NS5A inhibitor with excellent safety and tolerability in management of genotype 4
HCV patients.
PMID- 28707601
TI - Potential Role of Natural Compounds as Anti-Angiogenic Agents in Cancer.
AB - BACKGROUND: Neovascularization, also known as angiogenesis, is the process of
capillary sprouting from pre-existing blood vessels. This physiological process
is a hallmark event in normal embryonic development as blood vessels generally
supply both oxygen and nutrients to the cells of the body. Any disruption in this
process can lead to the development of various chronic diseases, including
cancer. In cancer, aberrant angiogenesis plays a prominent role in maintaining
sustained tumor growth to malignant phenotypes and promoting metastasis. The
leakiness in the tumor microvasculature is attributed to the tumor cells
migrating to distal site organs and forming colonies. METHODS: In this article,
we briefly review the various mediators involved in the angiogenic process and
the anti-angiogenic potential of selected natural compounds against various
malignancies. RESULTS: Several growth factors and their receptors such as
vascular endothelial growth factor and receptor (VEGF/VEGFR), basic fibroblast
growth factor and receptor (bFGF/FGFR), angiopoietins, and hypoxia inducible
factors facilitate the development of angiogenesis and are attractive anti-cancer
targets. Natural products represent a rich diversity of compounds for drug
discovery and are currently being actively exploited to target tumor
angiogenesis. CONCLUSION: Agents such as curcumin, artemisinin, EGCG,
resveratrol, emodin, celastrol, thymoquinone and tocotrienols all have shown
prominent anti-angiogenic effects in the preclinical models of tumor
angiogenesis. Several semi-synthetic derivatives and novel nano-formulations of
these natural compounds have also exhibited excellent anti-angiogenic activity by
increasing bioavailability and delivering the drugs to the sites of tumor
angiogenesis.
PMID- 28707602
TI - Ginkgo biloba Extract in Vascular Protection: Molecular Mechanisms and Clinical
Applications.
AB - BACKGROUND: Leaves of Ginkgo biloba, a "living fossil," have been used as
traditional herbal medicine for hundreds of years in China. Currently, its
application in vascular protection is garnering much attention. METHODS: In this
manuscript, preclinical studies were reviewed to discuss various mechanisms
underlying the vascular protection by Ginkgo biloba extract (GBE). Additionally,
we reviewed clinical studies to present the application of GBE in the ischaemic
disease. RESULTS: GBE, a commonly used dietary supplement, has been shown to act
as an antioxidant and freeradical scavenger, a membrane stabilizer, an inhibitor
of the platelet-activating factor, a vasodilator, and a regulator of metabolism.
Currently, there exist a growing number of clinical studies about GBE in the
application of cardiovascular disease, peripheral vascular disease (PVD) and
diabetic vascular complications. CONCLUSION: GBE, a promising therapeutic agent
for cardiovascular and ischaemic diseases, exerts vascular- protection function
by a comprehensive mechanisms.
PMID- 28707603
TI - Ginseng for Treating Hypertension: A Systematic Review and Meta-Analysis of
Double Blind, Randomized, Placebo-Controlled Trials.
AB - BACKGROUND: Evidence of ginseng for reducing blood pressure (BP) in hypertensive
patients is controversial. This systematic review updated the previous reviews
and evidence for it. METHODS: Ten databases were searched from their inception
through October 2016, without language restriction. Randomized clinical trials
(RCTs) were included if any types of ginseng were tested as the sole treatment or
as an adjunct to other treatments for pre-hypertension or hypertension. The risk
of bias (ROB) was assessed with Cochrane ROB tools by two independent reviewers.
RESULTS: We found 528 potentially relevant articles, of which 9 RCTs met our
inclusion criteria. Two studies reported positive effects of Korean red ginseng
(KRG) on acute reduction of systolic BP (SBP: n=54, mean differences (MD), -6.52;
P=0.0002; I2=0%) and diastolic BP DBP: MD, -5.21; P=0.0001; I2=0%), while two
other trials failed to do so with north American ginseng (NAG) in both SBP and
DBP. Five RCTs assessed the long-term effects of ginseng (KRG or NAG) on SBP and
DBP. Two studies showed positive effects of KRG on reducing SBP and DBP compared
with placebo (SBP: n = 183, MD, -2.92, P=0.04; I2 = 0%; DBP: MD, -3.19, P=0.008;
I2 = 0%). CONCLUSION: This systematic review provides positive evidence for the
efficacy of KRG on reducing blood pressure in patients with pre-hypertension and
hypertension in acute and long-term. Future RCTs appear to be warranted.
PMID- 28707604
TI - Chinese Herbal Medicine for Hyperlipidaemia: A Review Based on Data Mining from
1990 to 2016.
AB - BACKGROUND: Many studies have shown that the reduction of low density lipoprotein
(LDLC) levels provides cardiovascular protection; therefore LDL-C is considered
to be a core therapeutic target in anti-hyperlipidaemia treatment. However, the
LDL-C goal attainment is often not satisfied in China with conventional lipid
lowering agents. Many patients seek help from Chinese Herbal Medicine (CHM). To
further understand the current use of CHM in hyperlipidaemia, we conducted a
review based on a systematic literature search and data mining. METHODS: We
comprehensively searched MEDLINE, EBSCO, Cochrane Library, EMBASE, Chinese
Biomedical Literature Database (CBM), Chinese Scientific Journal Database (VIP),
China National Knowledge Infrastructure (CNKI) and Wanfang database to identify
potentially relevant articles. We included literatures that met the following
criteria: (1) randomized or non-randomized controlled trials; (2) observational
clinical trials; (3) case series or case reports. In order to enrich the
systematic literature searching and provide the quantitative relationship between
relative items and the treatment of hyperlipidaemia, the data mining was also
conducted by filtering the biomedical literature on hyperlipidaemia in SinoMed
and other available databases like VIP and CNKI. RESULTS: In summary, 282 records
of CHM on hyperlipidaemia were captured and analysed. The top used single herb
was Radix Salviae Miltiorrhizae. The most frequently used formula was Xuefuzhuyu
Decoction. The most used herbs in clinical practice have some pharmacological
evidences. The mechanisms are different, but could be classified into three
categories: inhibiting synthesis, increasing decomposition and reducing
absorption. CONCLUSION: CHM shows positive effect in the treatment of
hyperlipidaemia and has the potential to be used in combination with conventional
drugs. However, their use should be demonstrated in highquality clinical trials
and clinicians should pay attention to potential herb-drug interactions.
PMID- 28707605
TI - Self-reported use of nutrition labels to make food choices is associated with
healthier dietary behaviours in adolescents.
AB - OBJECTIVE: The study aimed to examine nutrition label use and dietary behaviours
among ethnically diverse middle- and high-school students, in Texas, USA. DESIGN:
The School Physical Activity and Nutrition (SPAN) survey is a cross-sectional
statewide study using a self-administered questionnaire to assess nutrition and
physical activity behaviours. Height and weight measurements were used to
determine BMI. Multivariable logistic regression was used to determine
associations between nutrition label use and dietary behaviours, with gender,
grade, ethnicity, BMI, parent education, socio-economic status and nutrition
knowledge as covariates. SETTING: Participants from 283 schools, weighted to
represent Texas youth. SUBJECTS: SPAN 2009-2011 included 6716 8th and 11th
graders (3465 girls and 3251 boys). The study population consisted of 39.83 %
White/Other, 14.61 % African-American and 45.56 % Hispanic adolescents; with a
mean age of 14.9 years, and 61.95 % at a healthy weight, 15.71 % having
overweight and 22.34 % having obesity. RESULTS: Adolescents who did not use
nutrition labels had 1.69 times greater odds of consuming >=1 sugary beverages/d
(P<0.05). Adolescents who used nutrition labels had 2.13 times greater odds of
consuming >=1 fruits and vegetables/d (P<0.05). Adolescents who used nutrition
labels had significantly higher healthy eating scores than those who did not
(P<0.001). For every 1-point increase in nutrition knowledge, adolescents had
1.22 greater odds of using nutrition labels. CONCLUSIONS: Nutrition label use is
associated with healthier dietary behaviours in adolescents. Intervention
strategies for youth should include efforts to teach adolescents to use labels to
make healthy food choices.
PMID- 28707606
TI - Evidence of positive selection towards Zebuine haplotypes in the BoLA region of
Brangus cattle.
AB - The Brangus breed was developed to combine the superior characteristics of both
of its founder breeds, Angus and Brahman. It combines the high adaptability to
tropical and subtropical environments, disease resistance, and overall hardiness
of Zebu cattle with the reproductive potential and carcass quality of Angus. It
is known that the major histocompatibility complex (MHC, also known as bovine
leucocyte antigen: BoLA), located on chromosome 23, encodes several genes
involved in the adaptive immune response and may be responsible for adaptation to
harsh environments. The objective of this work was to evaluate whether the local
breed ancestry percentages in the BoLA locus of a Brangus population diverged
from the estimated genome-wide proportions and to identify signatures of positive
selection in this genomic region. For this, 167 animals (100 Brangus, 45 Angus
and 22 Brahman) were genotyped using a high-density single nucleotide
polymorphism array. The local ancestry analysis showed that more than half of the
haplotypes (55.0%) shared a Brahman origin. This value was significantly
different from the global genome-wide proportion estimated by cluster analysis
(34.7% Brahman), and the proportion expected by pedigree (37.5% Brahman). The
analysis of selection signatures by genetic differentiation (F st ) and extended
haplotype homozygosity-based methods (iHS and Rsb) revealed 10 and seven
candidate regions, respectively. The analysis of the genes located within these
candidate regions showed mainly genes involved in immune response-related
pathway, while other genes and pathways were also observed (cell surface
signalling pathways, membrane proteins and ion-binding proteins). Our results
suggest that the BoLA region of Brangus cattle may have been enriched with
Brahman haplotypes as a consequence of selection processes to promote adaptation
to subtropical environments.
PMID- 28707607
TI - Processed and ultra-processed foods are associated with lower-quality nutrient
profiles in children from Colombia - CORRIGENDUM.
PMID- 28707608
TI - Atrial septal defect and an unusual anatomical variant of double-chambered right
ventricle presenting with cyanosis.
AB - We treated two patients with unexplained cyanosis, an atrial septal defect and an
unusual form of non-obstructive double-chambered right ventricle, with device
closure of the atrial septal defect.
PMID- 28707609
TI - The role of diet and nutrition on mental health and wellbeing.
AB - Mental, neurological and substance-use disorders presently represent the greatest
global burden of disease. Likewise, depression and other psychopathologies are
elevated risk comorbidities of other health hazards, such as obesity. Nutrition
has been implicated in behaviour, mood and in the pathology and treatment of
mental illness. In this brief editorial, we aim to set the scale of the problem
in context and overview advances and recent evidence linking nutrition to
psychological outcomes. The purpose of the 2016 Nutrition Society Winter Meeting,
'Diet, nutrition and mental health and wellbeing' was to review where the
evidence is strong, where there are unmet needs for research and to draw together
the communities working in this area to share their findings. The papers
presented demonstrated clear advancements that are being made in this field. The
meeting illustrated compelling support for nutrition as a modifiable risk factor.
The present research in the field and evidence presented at the 2016 Nutrition
Society Winter Meeting lead us to postulate that even interventions with
relatively modest effect sizes may plausibly and significantly curtail the
disease burden of mental and neurological disease by food- and nutrient-based
approaches.
PMID- 28707610
TI - Update on the Society for Disaster Medicine and Public Health.
PMID- 28707612
TI - Catechin Composition and Antioxidant Activity of Black Teas in Relation to
Brewing Time.
AB - Black tea infusions are one of the most popular beverages across the world. Their
extract composition depends on several factors, brewing time being one of the
most important determinants. The aim of the present study was to determine the
catechin composition of different black tea infusions using a validated LC
electrospray ionization time-of-flight MS method. Additionally, total phenolic
content (TPC) and antioxidant activity of infusions were evaluated using Folin
Ciocalteu reagent and stable radical 2,2-diphenyl-1-picrylhydrazyl (DPPH). An
optimized LC-MS method enabled the precise identification of the studied
catechins [epicatechin (EC), EC gallate (ECG), epigallocatechin (EGC), and
epigallocatechin-3-gallate (EGCG)] and gallic acid (GA). The major catechin in
all investigated teas was EGC (25.6 mg/100 cm3 after 4 min of brewing). EC was
present at the lowest concentration in all extracts. TPC and antiradical
scavenging activity were in a good agreement with catechins and GA content. In
general, the longer the brewing time, the higher the concentration of catechin,
TPC, and antioxidant activity values. However, it should be noted that after 2
min brewing, most phenolics had already been extracted, and extract composition
did not significantly change at a prolonged extraction time.
PMID- 28707613
TI - Metabolic Profile of and Antimicrobial Activity in the Aerial Part of Leonurus
turkestanicus V.I. Krecz. et Kuprian. from Kazakhstan.
AB - An HPLC quadrupole time-of-flight (Q-TOF) MS method was developed for the
identification of secondary metabolites in Leonurus turkestanicus V.I. Krecz. et
Kuprian. Ethanolic and chloroform extracts from the plant's aerial parts were
tested. A total of 16 compounds (iridoid glycosides, phenylpropanoids,
flavonoids, and nitrogen-containing compounds, as well as diterpene acetate
derivatives) were identified and tentatively characterized based on (or using)
their retention times and UV and Q-TOF-MS data. Previously reported aucubin (1),
6-deoxy-8-acetylharpagid (2), and stachydrine (13, 15) and homostachydrine
isomers (14, 16) were identified, along with a lavandulifolioside isomer (3),
verbascoside (4), rutin (5), 3-O-kaempferol rutinoside (6), and an unknown
diterpene acetate (8). Compounds 3-6 were detected for the first time in this
plant. Additionally. antimicrobial activity was evaluated. No significant
differences were found between ethanolic and chloroform extracts of L.
turkestanicus; however, the alcoholic extract showed stronger antifungal activity
[minimal inhibitory concentration (MIC) of 2.5-5 mg/mL], whereas the chloroform
extract showed stronger activity against the tested spore-forming Bacillus
species (MIC 1.25-2.5 mg/mL).
PMID- 28707614
TI - Determination of Curcuminoids in Turmeric Raw Materials and Dietary Supplements
by HPLC: Single-Laboratory Validation, First Action 2016.16.
AB - The AOAC Expert Review Panel (ERP) approved a method for the quantitation of
curcuminoids for consideration for First Action Official MethodSM status. The
previously published method summarized a single-laboratory validation of three
individual curcuminoinds-curcumin, demethoxycurcumin, and bis-demethoxycurcumin
in raw materials and finished products. Method performance was compared with AOAC
Standard Method Performance Requirement 2016.003. With repeatability precision
ranging from 0.3 to 5.5% and recoveries from 96.6 to 103.3% in the different
product matrixes, the ERP adopted the method and provided recommendations for
achieving Final Action status.
PMID- 28707615
TI - Determination of Adsorption Equations for Chloro Derivatives of Aniline on
Halloysite Adsorbents Using Inverse Liquid Chromatography.
AB - Chloro derivatives of aniline are commonly used in the production of dyes,
pharmaceuticals, and agricultural agents. They are toxic compounds with a large
accumulation ability and low natural biodegradability. Halloysite is known as an
efficient adsorbent of toxic compounds, such as phenols or herbicides, from
wastewater. Inverse LC was applied to measure the adsorption of aniline and 2
chloroaniline (2-CA), 3-chloroaniline (3-CA), and 4-chloroaniline (4-CA) on
halloysite adsorbents. A peak division (PD) method was used to determine a
Langmuir equation in accordance with the adsorption measurement results. The
values of adsorption equilibrium constants and enthalpy were determined and
compared by breakthrough curve and PD methods. The physical sense of the
calculated adsorption enthalpy values was checked by applying Boudart's entropy
criteria. Of note, adsorption enthalpy values for halloysite adsorbents decreased
in the following order: aniline > 4-CA > 2-CA > 3-CA.
PMID- 28707616
TI - Application of Mobile Phases Containing Ionic Liquid for HPLC Analysis of
Selected Isoquinoline Alkaloids.
AB - An HPLC procedure on a polar reversed-phase column with mobile phases containing
ionic liquid (IL) was developed for the analysis of selected alkaloids from
different chemical groups. We aimed to obtain optimal conditions for the
separation of alkaloids because widely used silica-based stationary phases
exhibit a silanol effect, rendering analysis of basic analytes extremely
difficult. Retention, separation selectivity, peak symmetry, and system
efficiency were examined in various eluent systems containing different
concentrations of IL and acetonitrile. The obtained results revealed substantial
influence from the concentrations of IL, the organic modifier, and temperature on
the retention behavior of the investigated alkaloids. The most selective and
efficient chromatographic systems were applied for the analysis of several
alkaloids in a plant extract.
PMID- 28707617
TI - Supercritical Fluid Extraction of Bioactive Compounds from Plant Materials.
AB - There has been growing interest in the application of supercritical solvents over
the last several years, many of the applications industrial in nature. The
purpose of plant material extraction is to obtain large amounts of extract rich
in the desired active compounds in a time-sensitive and cost-effective manner.
The productivity and profitability of a supercritical fluid extraction (SFE)
process largely depends on the selection of process parameters, which are
elaborated upon in this paper. Carbon dioxide (CO2) is the most desirable solvent
for the supercritical extraction of natural products. Its near-ambient critical
temperature makes it suitable for the extraction of thermolabile components
without degradation. A new approach has been adopted for SFE in which the
solubility of nonpolar supercritical CO2 can be enhanced by the addition of small
amounts of cosolvent.
PMID- 28707618
TI - How High Pressure Unifies Solvation Processes in Liquid Chromatography.
AB - A series of core-shell-based stationary phases of varying surface chemistry were
subjected to solvent adsorption investigation under ultra-HPLC conditions.
Acetonitrile and water excess isotherms were measured using a minor disturbance
method. It was observed that adsorption of organic solvent is unified under high
pressure. Preferential solvation due to specific interactions between the
stationary phases and solvent molecules was limited. The obtained results showed
that the solvation process is almost independent of surface chemistry, in
contrast to HPLC conditions in which specific interactions differentiate
solvation processes.
PMID- 28707619
TI - Evaluation of Gas Chromatography Stationary Phases Based on Morpholinium Ionic
Liquids by McReynolds Constants and Activity Coefficients at Infinite Dilution.
AB - In this work, four ionic liquids (ILs) based on the N-alkyl-N-methylmorpholinium
cation ([Mor1,R], in which R = 2, 4, 8, or 10) and
bis(trifluoromethanesulfonyl)imide anion were synthesized. Using GLC, a number of
parameters describing the sorption properties of the investigated ILs were
determined. The values of Kovats indices, McReynolds constants, and activity
coefficients at infinite dilution were the basis for the evaluation of
intermolecular interactions. The effect of the chain length of the alkyl
substituent in the cation, which was used to modify their polarity, has been
discussed. Comparison of the characteristics of the investigated IL-based
stationary phases with commercially available ones allowed for the statement that
the investigated ILs were more polar. The tested ILs had a relatively high
polarity. Increasing the length of the alkyl chain in the morpholinium ring
reduced polarity. ILs based on the morpholinium cation were tunable in a wide
range of their polarity.
PMID- 28707620
TI - A QuEChERS-Based Sample Preparation Method for the Analysis of 5-Nitroimidazoles
in Bovine Milk by HPLC-DAD.
AB - In this study, a simple, cost-effective, and sensitive HPLC diode-array detection
method was developed for the simultaneous determination of six different 5
nitroimidazoles [metronidazole, 2-hydroxymethyl-1-methyl-5-nitro-1H-imidazole,
dimetridazole (DMZ), ronidazole, ornidazole, and ipronidazole] in bovine milk
samples. A QuEChERS-based sample preparation procedure was optimized by
evaluating different cleanup sorbents, including zirconium-based sorbents (Z-Sep
and Z-Sep+), C18, and primary-secondary amine (PSA), as well as EMR-Lipid cleanup
solution. Acceptable analytical performance for all analytes was observed with
recoveries in the range of 45-93% and RSDs of less than 15%. Negligible matrix
interference was observed for most of the analytes due to application of PSA
sorbent in a dispersive solid-phase extraction cleanup step. Method LOQs (mLOQs)
for five of the six investigated analytes were set at a satisfactory low food
product value of 2.5 ng/mL. For DMZ only, the mLOQ was set at 10 ng/mL. The
procedure was evaluated through the analysis of 10 different natural samples.
PMID- 28707621
TI - Characterization of Low-Molecular-Weight Heparins by Strong Anion-Exchange
Chromatography.
AB - Currently, detailed structural characterization of low-molecular-weight heparin
(LMWH) products is an analytical subject of great interest. In this work, we
carried out a comprehensive structural analysis of LMWHs and applied a modified
pharmacopeial method, as well as methods developed by other researchers, to the
analysis of novel biosimilar LMWH products; and, for the first time, compared the
qualitative and quantitative composition of commercially available drugs
(enoxaparin, nadroparin, and dalteparin). For this purpose, we used strong anion
exchange (SAX) chromatography with spectrophotometric detection because this
method is more helpful, easier, and faster than other separation techniques for
the detailed disaccharide analysis of new LMWH drugs. In addition, we subjected
the obtained results to statistical analysis (factor analysis, t-test, and Newman
Keuls post hoc test).
PMID- 28707622
TI - Retention Models on Core-Shell Columns.
AB - A thin, active shell layer on core-shell columns provides high efficiency in HPLC
at moderately high pressures. We revisited three models of mobile phase effects
on retention for core-shell columns in mixed aqueous-organic mobile phases:
linear solvent strength and Snyder-Soczewinski two-parameter models and a three
parameter model. For some compounds, two-parameter models show minor deviations
from linearity due to neglect of possible minor retention in pure weak solvent,
which is compensated for in the three-parameter model, which does not explicitly
assume either the adsorption or the partition retention mechanism in normal- or
reversed-phase systems. The model retention equation can be formulated as a
function of solute retention factors of nonionic compounds in pure organic
solvent and in pure water (or aqueous buffer) and of the volume fraction of an
either aqueous or organic solvent component in a two-component mobile phase. With
core-shell columns, the impervious solid core does not participate in the
retention process. Hence, the thermodynamic retention factors, defined as the
ratio of the mass of the analyte mass contained in the stationary phase to its
mass in the mobile phase in the column, should not include the particle core
volume. The values of the thermodynamic factors are lower than the retention
factors determined using a convention including the inert core in the stationary
phase. However, both conventions produce correct results if consistently used to
predict the effects of changing mobile phase composition on retention. We
compared three types of core-shell columns with C18-, phenyl-hexyl-, and biphenyl
bonded phases. The core-shell columns with phenyl-hexyl- and biphenyl-bonded
ligands provided lower errors in two-parameter model predictions for
alkylbenzenes, phenolic acids, and flavonoid compounds in comparison with C18
bonded ligands.
PMID- 28707623
TI - Trapping charges at grain boundaries and degradation of CH3NH3Pb(I1-x Br x )3
perovskite solar cells.
AB - The electrical properties of CH3NH3Pb(I1-x Br x )3 (x = 0.13) perovskite
materials were investigated under ambient conditions. The local work function and
the local current were measured using Kelvin probe force microscopy and
conductive atomic force microscopy, respectively. The degradation of the
perovskite layers depends on their grain size. As the material degrades, an
additional peak in the surface potential appears simultaneously with a sudden
increase and subsequent relaxation of the local current. The potential bending at
the grain boundaries and the intragrains is the most likely reason for the change
of the local current surface of the perovskite layers. The improved understanding
of the degradation mechanism garnered from this study helps pave the way toward
an improved photo-conversion efficiency in perovskite solar cells.
PMID- 28707624
TI - Three-dimensional (3D) culture in sarcoma research and the clinical significance.
AB - Sarcomas are rare malignant tumors that arise from transformed cells of
mesenchymal origin. Despite the progress in diagnosis and treatment, sarcomas
have a high mortality rate due to local recurrence, metastasis, and the
development of drug resistance to chemotherapy. New models for sarcoma research
are required to further understand the disease and to develop new therapies. In
vitro sarcoma modeling is challenging because of significant genetic
heterogeneities, diverse pathological, and overlapping clinical characteristics.
Studies on the mechanisms of recurrence, metastasis, and drug resistance in
sarcoma have resulted in the generation of novel three-dimensional (3D) culture
models for sarcoma research. 3D culture models aim to recapitulate the tumor
microenvironment that plays a critical role in the pathogenesis of sarcoma using
biomaterial scaffolds of natural biological materials and artificial polymers. An
ideal 3D culture model can properly mimic not only the microenvironment,
oncogenesis, and maintenance of sarcoma cell growth, but also imitate the
interactions between cells and to the extracellular matrix. More recently, 3D
cell culture has been used to research the biological behavior and mechanism of
chemotherapy and radiotherapy resistance in different sarcoma models. Ultimately,
findings using 3D models that more accurately reflect human sarcoma biology are
likely to translate into improved clinical outcomes. In this review, we discuss
the most recent advances of 3D culture technologies in sarcoma research and
emerging clinical applications.
PMID- 28707625
TI - Bioprinting of a functional vascularized mouse thyroid gland construct.
AB - Bioprinting can be defined as additive biofabrication of three-dimensional (3D)
tissues and organ constructs using tissue spheroids, capable of self-assembly, as
building blocks. The thyroid gland, a relatively simple endocrine organ, is
suitable for testing the proposed bioprinting technology. Here we report the
bioprinting of a functional vascularized mouse thyroid gland construct from
embryonic tissue spheroids as a proof of concept. Based on the self-assembly
principle, we generated thyroid tissue starting from thyroid spheroids (TS) and
allantoic spheroids (AS) as a source of thyrocytes and endothelial cells (EC),
respectively. Inspired by mathematical modeling of spheroid fusion, we used an
original 3D bioprinter to print TS in close association with AS within a collagen
hydrogel. During the culture, closely placed embryonic tissue spheroids fused
into a single integral construct, EC from AS invaded and vascularized TS, and
epithelial cells from the TS progressively formed follicles. In this experimental
setting, we observed formation of a capillary network around follicular cells, as
observed during in utero thyroid development when thyroid epithelium controls the
recruitment, invasion and expansion of EC around follicles. To prove that EC from
AS are responsible for vascularization of the thyroid gland construct, we
depleted endogenous EC from TS before bioprinting. EC from AS completely
revascularized depleted thyroid tissue. The cultured bioprinted construct was
functional as it could normalize blood thyroxine levels and body temperature
after grafting under the kidney capsule of hypothyroid mice. Bioprinting of
functional vascularized mouse thyroid gland construct represents a further
advance in bioprinting technology, exploring the self-assembling properties of
tissue spheroids.
PMID- 28707626
TI - Performance of neural networks for localizing moving objects with an artificial
lateral line.
AB - Fish are able to sense water flow velocities relative to their body with their
mechanoreceptive lateral line organ. This organ consists of an array of flow
detectors distributed along the fish body. Using the excitation of these
individual detectors, fish can determine the location of nearby moving objects.
Inspired by this sensory modality, it is shown here how neural networks can be
used to extract an object's location from simulated excitation patterns, as can
be measured along arrays of stationary artificial flow velocity sensors. The
applicability, performance and robustness with respect to input noise of
different neural network architectures are compared. When trained and tested
under high signal to noise conditions (46 dB), the Extreme Learning Machine
architecture performs best with a mean Euclidean error of 0.4% of the maximum
depth of the field D, which is taken half the length of the sensor array. Under
lower signal to noise conditions Echo State Networks, having recurrent
connections, enhance the performance while the Multilayer Perceptron is shown to
be the most noise robust architecture. Neural network performance decreased when
the source moves close to the sensor array or to the sides of the array. For all
considered architectures, increasing the number of detectors per array increased
localization performance and robustness.
PMID- 28707627
TI - Mussel-inspired nano-building block assemblies for mimicking extracellular matrix
microenvironments with multiple functions.
AB - The assembly of nano-building blocks is an effective way to produce artificial
extracellular matrix microenvironments with hierarchical micro/nano structures.
However, it is hard to assemble different types of nano-building blocks, to form
composite coatings with multiple functions, by traditional layer-by-layer (LbL)
self-assembly methods. Inspired by the mussel adhesion mechanism, we developed
polydopamine (PDA)-decorated bovine serum albumin microspheres (BSA-MS) and nano
hydroxyapatite (nano-HA), and assembled them to form bioactive coatings with
micro/nano structures encapsulating bone morphogenetic protein-2 (BMP-2). First,
PDA-decorated nano-HA (nano-pHA) was obtained by oxidative polymerization of
dopamine on nano-HA. Second, BMP-2-encapsulated BSA microspheres were prepared
through desolvation, and then were also decorated by PDA (pBSA-MS). Finally, the
nano-pHA and pBSA-MS were assembled using the adhesive properties of PDA. Bone
marrow stromal cell cultures and in vivo implantation, showed that the pHA/pBSA
(BMP-2) coatings can promote cell adhesion, proliferation, and benefited for
osteoinductivity. PDA decoration was also applied to assemble various functional
nanoparticles, such as nano-HA, polystyrene, and Fe3O4 nanoparticles. In summary,
this study provides a novel strategy for the assembly of biofunctional nano
building blocks, which surpasses traditional LbL self-assembly of
polyelectrolytes, and can find broad applications in bioactive agents delivery or
multi-functional coatings.
PMID- 28707628
TI - BrainFrame: a node-level heterogeneous accelerator platform for neuron
simulations.
AB - OBJECTIVE: The advent of high-performance computing (HPC) in recent years has led
to its increasing use in brain studies through computational models. The scale
and complexity of such models are constantly increasing, leading to challenging
computational requirements. Even though modern HPC platforms can often deal with
such challenges, the vast diversity of the modeling field does not permit for a
homogeneous acceleration platform to effectively address the complete array of
modeling requirements. APPROACH: In this paper we propose and build BrainFrame, a
heterogeneous acceleration platform that incorporates three distinct acceleration
technologies, an Intel Xeon-Phi CPU, a NVidia GP-GPU and a Maxeler Dataflow
Engine. The PyNN software framework is also integrated into the platform. As a
challenging proof of concept, we analyze the performance of BrainFrame on
different experiment instances of a state-of-the-art neuron model, representing
the inferior-olivary nucleus using a biophysically-meaningful, extended Hodgkin
Huxley representation. The model instances take into account not only the
neuronal-network dimensions but also different network-connectivity densities,
which can drastically affect the workload's performance characteristics. MAIN
RESULTS: The combined use of different HPC technologies demonstrates that
BrainFrame is better able to cope with the modeling diversity encountered in
realistic experiments while at the same time running on significantly lower
energy budgets. Our performance analysis clearly shows that the model directly
affects performance and all three technologies are required to cope with all the
model use cases. SIGNIFICANCE: The BrainFrame framework is designed to
transparently configure and select the appropriate back-end accelerator
technology for use per simulation run. The PyNN integration provides a familiar
bridge to the vast number of models already available. Additionally, it gives a
clear roadmap for extending the platform support beyond the proof of concept,
with improved usability and directly useful features to the computational
neuroscience community, paving the way for wider adoption.
PMID- 28707630
TI - How innovative and conventional curricula prepare medical students for practice
in Sub-Saharan Africa: A comparative study from Mozambique.
AB - BACKGROUND: Medical education in Sub-Saharan Africa is in need of reform to
promote the number and quality of physicians trained. Curriculum change and
innovation in this region, however, face a challenging context that may affect
curriculum outcomes. Research on outcomes of curriculum innovation in Sub-Saharan
Africa is scarce. We investigated curriculum outcomes in a Sub-Saharan African
context by comparing students' perceived preparedness for practice within three
curricula in Mozambique: a conventional curriculum and two innovative curricula.
Both innovative curricula used problem-based learning and community-based
education. METHODS: We conducted a comparative mixed methods study. We adapted a
validated questionnaire on perceived professional competencies and administered
it to 5th year students of the three curricula (n = 140). We conducted semi
structured interviews with 5th year students from these curricula (n = 12).
Additional contextual information was collected. Statistical and thematic
analyses were conducted. RESULTS: Perceived preparedness for practice of students
from the conventional curriculum was significantly lower than for students from
one innovative curriculum, but significantly higher than for students from the
other innovative curriculum. Major human and material resource issues and
disorganization impeded the latter's sense of preparedness. Both innovative
curricula, however, stimulated a more holistic approach among students toward
patients, as well an inquiring and independent attitude, which is valuable
preparation for Sub-Saharan African healthcare. DISCUSSION: In Sub-Saharan
Africa, risks and benefits of curriculum innovation are high. Positive outcomes
add value to local healthcare in terms of doctors' meaningful preparedness for
practice, but instead outcomes can be negative due to the implementation
challenges sometimes found in Sub-Saharan African contexts. Before embarking on
innovative curriculum reform, medical schools need to assess their capability and
motivation for innovation.
PMID- 28707631
TI - "In our own words": Defining medical professionalism from a Latin American
perspective.
AB - BACKGROUND: Latin America has experienced a tremendous growth in a number of
medical schools, and there are concerns about their quality of training in
critical areas such as professionalism. Medical professionalism is a cultural
construct. The aim of the study was to compare published definitions of medical
professionalism from Latin American and non-Latin American regions and to design
an original and culturally sound definition. METHODS: A mixed methods approach
was used with three phases. First, a systematic search and thematic analysis of
the literature were conducted. Second, a Delphi methodology was used to design a
local definition of medical professionalism. Third, we used a qualitative
approach that combined focus groups and personal interviews with students and
deans from four medical schools in Chile to understand various aspects of
professionalism education. The data were analyzed using NVivo software. RESULTS:
A total of 115 nonrepeated articles were identified in the three databases
searched. No original definitions of medical professionalism from Latin America
were found. Twenty-six articles met at least one of the three decisional criteria
defined and were fully reviewed. Three theoretical perspectives were identified:
contractualism, personalism, and deontology. Attributes of medical
professionalism were classified in five dimensions: personal, interpersonal,
societal, formative, and practical. Participants of the Delphi panel, focus
groups, and personal interviews included 36 medical students, 12 faculties, and
four deans. They took a personalistic approach to design an original definition
of medical professionalism and highlighted the relevance of respecting life,
human dignity, and the virtue of prudence in medical practice. Students and
scholars differed on the value given to empathy and compassion. DISCUSSION: This
study provides an original and culturally sound definition of medical
professionalism that could be useful in Latin American medical schools. The
methodology used in the study could be applied in other regions as a basis to
develop culturally appropriate definitions of medical professionalism.
PMID- 28707632
TI - Patients' perceptions of argentine physicians' empathy based on the jefferson
scale of patient's perceptions of physician empathy: Psychometric data and
demographic differences.
AB - BACKGROUND: The aim of this study was to evaluate the validity of a modified
Spanish version of the Jefferson Scale of Patient's Perceptions of Physician
Empathy (JSPPPE) in Argentine patients and to explore how local demographic
characteristics influence patients' perceptions of their physicians' empathy.
METHODS: A survey was conducted in March 2013 among 400 Spanish-speaking
outpatients attending three different public or private hospitals of Buenos
Aires. A principal component analysis (PCA) was used to identify the JSPPPE
factor structure, and a confirmatory factor analysis (CFA) was employed to
evaluate its construct validity. Demographic variables including age, gender,
geographic origin, education, health coverage, regular physician-established and
patient-perceived health status were used to find what factors may influence
empathy rating. RESULTS: The PCA yielded a one-factor model that accounted for
77.5% of the variance, and an adequate model fit was observed with CFA indices.
Male and elderly patients, South American descendants, less educated people, and
public hospital attendants were associated with a higher JSPPPE score. Patients
perceived a lower interest of physicians in their daily problems and a poorer
capacity "to stand in their shoes." DISCUSSION: The JSPPPE provides a valid score
to measure patients' perceptions of physician empathy in Argentina. These
findings afford insight into Argentine patients' awareness of their doctors'
empathic concern; however, JSPPPE scores may be alternatively interpreted in
terms of patients' satisfaction or likeability.
PMID- 28707633
TI - Using a personality inventory to identify risk of distress and burnout among
early stage medical students.
AB - BACKGROUND: Distress and burnout are common among medical students and negatively
impact students' physical, mental, and emotional health. Personality inventories
such as the Myers-Briggs Type Indicator (MBTI), used in medical education, may
have a role in identifying burnout risk early. METHODS: The authors conducted a
cross-sectional survey study among 185 1st year medical students with the MBTI,
the general well-being schedule (GWB), and Maslach Burnout Inventory-Student
Survey (MBI-SS). Descriptive statistics and one-way MANOVAs were used to identify
the prevalence and differences in MBTI preferences and distress/burnout risk.
RESULTS: Response rate was 185/185 (100%). Distress (GWB) was reported by 84/185
(45.4%). High scores on exhaustion were reported by 118/182 (64.8%), cynicism by
76/182 (41.8%), and decreased professional efficacy by 38/182 (20.9%) for the
three dimensions of the MBI-SS. Only 21/182 (11.5%) of respondents had high
scores on all three dimensions of burnout. Students with MBTI preferences for
extraversion reported greater positive well-being (P < 0.05), self-control (P <
0.05), professional efficacy (P < 0.01), and lower levels of depression (P <
0.01) compared with those with introversion preference. DISCUSSION: Distress and
burnout are prevalent early in medical training. The significant difference
between extraversion and introversion in relation to distress and burnout
deserves further study. Use of a personality inventory may help identify students
at risk of burnout and allow appropriate early stress management.
PMID- 28707634
TI - Mobile learning app: A novel method to teach clinical decision making in
prosthodontics.
AB - BACKGROUND: Prosthodontics involves replacing lost dentofacial structures using
artificial substitutes. Due to availability of many materials and techniques,
clinician's clinical decision-making regarding appropriate selection of
prosthesis requires critical thinking abilities and is demanding. Especially
during graduate training years, learners do not receive the exposure to a variety
of cases, thus their clinical reasoning skills are not developed optimally.
Therefore, using the trend of incorporating technology in education, we developed
a mobile learning app for this purpose. The aim of this study was to evaluate
learners' perceptions of this app's utility and impact on their clinical decision
making skills. METHODS: After taking informed consent, interns of the Department
of Prosthodontics of VSPM Dental College, Nagpur, India, during the academic year
May 2015-May 2016 were sent the link for the app to be installed in their Android
smartphones. Their perceptions were recorded on a feedback questionnaire using 5
point Likert scale. The script concordance test (SCT) was used to check for
changes in clinical reasoning abilities. RESULTS: Out of 120 students who were
sent the link, 102 downloaded the link and 92 completed the feedback
questionnaire and appeared for the SCT (response rate: 76%). The overall response
to the app was positive for more than two-thirds of interns, who reported a
greater confidence in their clinical decision-making around prostheses through
this app and 94% of the students felt that this app should be regularly used
along with conventional teaching techniques. Mean SCT scores were pretest 41.5
(+/-1.7) and posttest 63 (+/-2.4) (P < 0.005). DISCUSSION: Clinical decision
making in prosthodontics, a mobile learning app, is an effective way to improve
clinical reasoning skills for planning prosthodontic rehabilitation. It is well
received by students.
PMID- 28707635
TI - Medical ethics education in China: Lessons from three schools.
AB - BACKGROUND: Ethics teaching is a relatively new area of medical education in
China, with ethics curricula at different levels of development. This study
examined ethics education at three medical schools in China to understand their
curricular content, teaching and learning methods, forms of assessments, changes
over time, and what changes are needed for further improvement. METHODS: We used
student and faculty surveys to obtain information about the ethics courses'
content, teaching methods, and revisions over time. The surveys also included
five realistic cases and asked participants whether each would be appropriate to
use for discussion in ethics courses. Students rated the cases on a scale and
gave written comments. Finally, participants were asked to indicate how much they
would agree with the statement that medical professionalism is about putting the
interests of patients and society above one's own. RESULTS: There were both
similarities and differences among these schools with regard to course topics,
teaching and assessment methods, and course faculty compositions, suggesting
their courses are at different levels of development. Areas of improvement for
the schools' courses were identified based on this study's findings and available
literature. A model of the evolution of medical ethics education in China was
proposed to guide reform in medical ethics instruction in China. Analysis
identified characteristics of appropriate cases and participants' attitudes
toward the ideal of professionalism. DISCUSSION: We conclude that the development
of medical ethics education in China is promising while much improvement is
needed. In addition, ethics education is not confined to the walls of medical
schools; the society at large can have significant influence on the formation of
students' professional values.
PMID- 28707636
TI - Implementation and evaluation of a patient safety course in a problem-based
learning program.
AB - BACKGROUND: Since the development of the WHO patient safety curriculum guide,
there has been insufficient reporting regarding the implementation and evaluation
of patient safety courses in undergraduate problem-based learning (PBL) programs.
This study is designed to implement a patient safety course to undergraduate
students in a PBL medical school and evaluate this course by examining its
effects on students' knowledge and satisfaction. METHODS: The target population
included year 6 medical students (n = 71) at the Faculty of Medicine, Suez Canal
University in Egypt. A 3-day course was conducted addressing three principal
topics from the WHO patient safety curriculum guide. The methods of instruction
included reflection on students' past experiences, PBL case discussions, and
tasks with incident report cards. A pre- and post-test design was used to assess
the effect of the course on students' knowledge of inpatient safety topics.
Furthermore, students' perceptions of the quality of the course were assessed
through a structured self-administered course evaluation questionnaire. RESULTS:
The results of the pre- and post-test demonstrated a significant increase (P <
0.05) in the students' mean multiple choice question (MCQ) scores. The MCQ scores
for "what is patient safety" topic increased by 50% (P < 0.01). Similarly, the
MCQ scores for the "infection control" topic increased by 39% (P < 0.01), and
scores for the "medication safety" topic increased by 45% (P < 0.01). The
majority of students perceived the different aspects of the course positively,
including the structure and introduction of the course (75%) and the
communication skills (83.2%) and teamwork skills they had developed (94.4%). The
findings of the incident report cards indicated that 46.7% of the students
perceived that incidents most commonly take place in the emergency room while
only 6.7% in the outpatient clinic. DISCUSSION: This patient safety education
program within a PBL curriculum is positively perceived by students. Furthermore,
patient safety education in clinical settings should focus on emergencies, where
students perceive most errors.
PMID- 28707637
TI - Implementation and sex-specific analysis of students' attitudes toward a
longitudinal, gender-specific medical curriculum - a pilot study.
AB - BACKGROUND: Gender medicine has gained importance over the past 20 years.
Nevertheless, the scientific findings concerning gender- and sex-specific patient
care have not been sufficiently integrated into the education of physicians. It
was therefore our aim, against initial resistance in our school, to integrate
clinically relevant aspects of gender medicine into the existing medical
curriculum. This paper describes the implementation process of a lecture-based
interdisciplinary, longitudinal, basic gender curriculum and evaluates students'
attitudes in relation to sex and semester level. METHODS: The curriculum
encompasses 15 lecture sessions scheduled in years 1 through 5 of the medical
curriculum at Ulm University, Germany. Prospectively gathered evaluation data of
two cross-sectional analyses of this basic curriculum in the first and fifth
semesters are analyzed by sex. RESULTS: More than 80% of the students have
registered for this new curriculum. Evaluation data show a predominantly positive
(75.5%) student response; however, only about half of those surveyed indicated
that they had learned new material or judged the content on gender to be relevant
to their practice of medicine. Students at a more advanced semester level (88.2%
vs. 55.2%) and male participants more than female participants (36.7% vs. 62.4%)
showed lower acceptance. DISCUSSION: It was possible to integrate gender issues
into the existing medical student curriculum. Despite the overall positive
rating, our evaluation data identified the aspects of rejection and resistance in
some students, particularly male and more advanced students. Further studies on
the development of student attitudes toward gender issues are needed.
PMID- 28707638
TI - Mimicking rashes: Use of moulage technique in undergraduate assessment at the aga
khan university, Karachi.
AB - BACKGROUND: The use of simulated patients in student assessment is supported by
the Best Evidence Medical Education and U.S. Agency for Healthcare Research and
Quality, and it provides a safe and effective alternative to real patients in
many situations. To assess the validity and feasibility of moulage technique
where a cosmetically constructed rash is used on simulated patients-two
dermatologic rashes were developed using moulage simulation on standardized
patients at Aga Khan University Hospital for 3rd year medical summative Objective
Structured Clinical Examination (OSCE). METHODS: Checklists for cases that
focused on history taking of a skin rash were developed. These also included a
description and identification of lesions, differential diagnosis, and basic
management. Cases were first reviewed and approved by the Educational Committee
and a dermatologist content expert. Stations were piloted to assess validity and
feasibility. Simple nontoxic materials were used to develop the rash by faculty
familiar with moulage simulation. RESULTS: Sixty-four students were assessed on a
Herpes Zoster case and 32 students on a Herpes Simplex case in morning and
afternoon sessions. The total mean score obtained at all OSCE stations was 64.82
+/- 10.22. Mean scores on the morning and afternoon dermatology stations were
62.72 +/- 9.74 and 69.03 +/- 9.98, respectively. Face validity for both stations
was established through input of content experts. The internal reliability as
measured by Cronbach's alpha between the checklist items on the morning and
afternoon stations was acceptable at 0.60 (20 items) and 0.65 (18 items),
respectively. DISCUSSION: The use of moulage technique to develop dermatologic
lesions on simulated patients may be utilized for student assessment.
PMID- 28707639
TI - Life in unexpected places: Employing visual thinking strategies in global health
training.
AB - BACKGROUND: The desire to make meaning out of images, metaphor, and other
representations indicates higher-order cognitive skills that can be difficult to
teach, especially in the complex and unfamiliar environments like those
encountered in many global health experiences. Because reflecting on art can help
develop medical students' imaginative and interpretive skills, we used visual
thinking strategies (VTS) during an immersive 4-week global health elective for
medical students to help them construct new understanding of the social
determinants of health in a low-resource setting. We were aware of no previous
formal efforts to use art in global health training. METHODS: We assembled a
group of eight medical students in front of a street mural in Kathmandu and used
VTS methods to interpret the scene with respect to the social determinants of
health. We recorded and transcribed the conversation and conducted a thematic
analysis of student responses. RESULTS: Students shared observations about the
mural in a supportive, nonjudgmental fashion. Two main themes emerged from their
observations: those of human-environment interactions (specifically community
dynamics, subsistence land use, resources, and health) and entrapment/control,
particularly relating to expectations of, and demands on, women in traditional
farming communities. They used the images as well as their experience in Nepali
communities to consolidate complex community health concepts. DISCUSSION: VTS
helped students articulate their deepening understanding of the social
determinants of health in Nepal, suggesting that reflection on visual art can
help learners apply, analyze, and evaluate complex concepts in global health. We
demonstrate the relevance of drawing upon many aspects of cultural learning,
regarding art as a kind of text that holds valuable information. These findings
may help provide innovative opportunities for teaching and evaluating global
health training in the future.
PMID- 28707640
TI - What do faculty feel about teaching in this school? assessment of medical
education environment by teachers.
AB - BACKGROUND: Faculty members are major stakeholders in curriculum delivery, and
positive student learning outcomes can only be expected in an educational
environment (EE) conducive to learning. EE experienced by teachers includes all
conditions affecting teaching and learning activities. As the EE of teachers
indirectly influences the EE of students, assessment of teachers' perceptions of
EE can highlight issues affecting student learning. These perceptions can also
serve as a valuable tool for identifying faculty development needs. In this
study, we have used the Assessment of Medical Education Environment by Teachers
(AMEET) inventory as a tool to assess medical teachers' perceptions of the EE.
METHODS: The AMEET inventory was used to assess perceptions regarding various
domains of EE by teachers teaching undergraduate students at the College of
Medicine, Gulf Medical University, Ajman, United Arab Emirates. Median total,
domain, and individual statement scores were compared between groups using
Wilcoxon rank-sum test. RESULTS: Teaching-learning activities, learning
atmosphere, collaborative atmosphere, and professional self-perceptions were
identified as strengths of the EE while time allocated for various teaching
learning activities, preparedness of students, levels of student stress, learning
atmosphere in hospital, and support system for stressed faculty members were
areas necessitating improvement. The scores of faculty members teaching in basic
medical sciences were found to be significantly higher than those in clinical
sciences. DISCUSSION: The EE of this medical college was generally perceived as
being positive by faculty although a few areas of concern were highlighted.
Strengths and weaknesses of the EE from the teachers' point of view provide
important feedback to curriculum planners, which can be used to improve the
working environment of the faculty as well as facilitate a better direction and
focus to faculty development programs being planned for the future.
PMID- 28707641
TI - Comparing the academic performance of graduate-entry and undergraduate medical
students at a UK medical school.
AB - BACKGROUND: The aim of the study was to assess whether graduate-entry (GE)
medicine is a valid route to medical school in the United Kingdom. We set out to
analyze the academic performance of GE students when compared with undergraduate
(UG) students by assessing the representation of high achievers and students with
fail grades within the two cohorts. METHODS: Using the Freedom of Information
Act, we requested examination result data for the academic year 2013-2014 at St.
George's Medical School, London, UK. We analyzed the number of students gaining
distinction (top 7.5%) and those in the first two deciles. RESULTS: There were
389 GE and 548 UG students in the clinical years. A total of 61.3% of the first
or second decile places were awarded to GEs, with 38.7% going to UGs (P <
0.0005). The proportion of GEs achieving the first or second decile was 30.1%
compared to 12.8% of UGs (P < 0.01). The proportion of GEs awarded distinction
was 12.3% compared to 2.9% of UGs (P < 0.02). The total number of students
failing a year at the first attempt was 103. The failure rate within each group
was 12.1% for GE and 10.2% for UG. DISCUSSION: Our study found that GE students
were overrepresented in the high-achieving groups when compared to UG students.
GE students were significantly more likely to be placed in the first or second
decile or attain a distinction award. However, GE and UG have a similar failure
rate. This study shows that GE programs are a valid entry route to medical
courses in the UK.
PMID- 28707642
TI - Teaching procedural skills to medical students: A pilot procedural skills lab.
AB - BACKGROUND: Medical students have limited confidence in performing procedural
skills. A pilot study was conducted to evaluate the effect of a multifaceted
Procedural Skills Lab (PSL) on the confidence of medical students to perform
procedural skills. METHODS: Twelve 2nd year medical students were randomly
selected to participate in a pilot PSL. The PSL students met with an instructor
for 2 h once a week for 4 weeks. Students participated in a flipped classroom and
spaced education program before laboratory sessions that included a cadaver
laboratory. Procedural skills included a focused assessment with sonography in
trauma (FAST) scan, cardiac echocardiogram, lumbar puncture, arthrocentesis, and
insertion of intraosseous and intravenous catheters. Students in the PSL were
asked to rank their confidence in performing procedural skills before and after
completion of the laboratory sessions (Wilcoxon ranked-sum test). A web-based
questionnaire was also emailed to all 2nd year medical students to establish a
baseline frequency for observing, performing, and confidence performing
procedural skills (Mann-Whitney U-test). RESULTS: Fifty-nine percent (n = 106) of
180 2nd year medical students (n = 12 PSL students [treatment group], n = 94
[control group]) completed the survey. Frequency of observation, performance, and
confidence in performing procedural skills was similar between the control and
treatment groups at baseline. There was an increased confidence level (p < 0.001)
for performing all procedural skills for the treatment group after completion of
the PSL. DISCUSSION: An innovative PSL may increase students' confidence to
perform procedural skills. Future studies will examine competency after a PSL.
PMID- 28707643
TI - Assessing reading levels of health information: uses and limitations of flesch
formula.
AB - BACKGROUND: Written health information is commonly used by health-care
professionals (HCPs) to inform and assess patients in clinical practice. With
growing self-management of many health conditions and increased information
seeking behavior among patients, there is a greater stress on HCPs and
researchers to develop and implement readable and understandable health
information. Readability formulas such as Flesch Reading Ease (FRE) and Flesch
Kincaid Reading Grade Level (FKRGL) are commonly used by researchers and HCPs to
assess if health information is reading grade appropriate for patients. PURPOSE:
In this article, we critically analyze the role and credibility of Flesch formula
in assessing the reading level of written health information. DISCUSSION: FRE and
FKRGL assign a grade level by measuring semantic and syntactic difficulty. They
serve as a simple tool that provides some information about the potential
literacy difficulty of written health information. However, health information
documents often involve complex medical words and may incorporate pictures and
tables to improve the legibility. In their assessments, FRE and FKRGL do not take
into account (1) document factors (layout, pictures and charts, color, font,
spacing, legibility, and grammar), (2) person factors (education level,
comprehension, health literacy, motivation, prior knowledge, information needs,
anxiety levels), and (3) style of writing (cultural sensitivity,
comprehensiveness, and appropriateness), and thus, inadequately assess reading
level. New readability measures incorporate pictures and use complex algorithms
to assess reading level but are only moderately used in health-care research and
not in clinical practice. Future research needs to develop generic and disease
specific readability measures to evaluate comprehension of a written document
based on individuals' literacy levels, cultural background, and knowledge of
disease.
PMID- 28707644
TI - Going the extra mile: Lessons learned from running coaches applied to medicine.
AB - Master clinicians and successful long-distance runners have a lot in common. Both
are dedicated to continuous improvement and are flexible in their approach,
allowing for adaptation to meet unplanned challenges. Given these similarities
and the important role of coaches in athletics, there is an opportunity for
medical educators to learn from excellent running coaching. The authors spent
time with three respected running coaches at different levels (high school,
college, and postcollegiate online) and identified six principles employed by
these coaches that seem to be particularly relevant for promoting skill
development in medicine. Three of these may be considered foundational tenets for
a successful coach: know your coachee; model the qualities you seek to instill;
and communicate clearly and consistently. An additional three principles
represent higher order coaching skills that enable superior coaches to develop
others into truly outstanding performers: be a keen observer; purposefully build
strong and interconnected teams; and inspire greatness. Longitudinal,
individualized coaching predicated on these six tenets may be an effective means
for optimizing professional development in medicine.
PMID- 28707645
TI - Students for students: The polish initiative for enhancing medical research
knowledge.
PMID- 28707646
TI - Massively open online courses and ophthalmology training.
PMID- 28707647
TI - Pilot evaluation of medical student perception of a novel pharmacology-based role
play game: Braincept.
PMID- 28707648
TI - Collaboration between a medical school and the provincial government health
system in effective implementation of a problem-based curriculum: An experience
from Saudi Arabia.
PMID- 28707649
TI - Receptor for advanced glycation end products is overexpressed in psoriatic
plaques independent of disease severity.
AB - BACKGROUND: Enhanced expression and excitation of the receptor for advanced
glycation end products is considered to play a role in the regulation of many pro
inflammatory genes involved in the pathogenesis of psoriasis. AIM: We
investigated the expression of receptor for advanced glycation end product in
various cell types, in lesional and peri-lesional skin of patients with
psoriasis, and its correlation with disease severity. METHODS: Paraffin-embedded
punch biopsy tissue taken from psoriatic plaques and peri-lesional normal
appearing skin tissue of twenty patients with psoriasis, and normal skin samples
of eleven healthy participants, were enrolled in the study. The sections were
stained immunohistochemically with anti-receptor for advanced glycation end
product antibody. The intensity of receptor for advanced glycation end product
expression was assessed semi-quantitatively on epidermal cells, microvascular
endothelium, dermal fibroblasts and inflammatory cells. They were graded as
follows: 0 (no staining), 1 (weak), 2 (moderate) and 3 (strong) intensity.
RESULTS: Receptor for advanced glycation end product expression on epidermis,
microvascular endothelium, inflammatory cells and fibroblasts in the psoriatic
plaques was more intense than perilesional and normal tissue (all P < 0.05). It
did not correlate with disease severity. LIMITATIONS: The main limitation of our
study is that this was a semi-quantitative assessment, detected
immunohistochemically in skin biopsies. CONCLUSION: Receptor for advanced
glycation end product expression may have an important role in psoriasis
pathogenesis, independent of disease severity.
PMID- 28707650
TI - Disseminated discoid lupus erythematosus with a linear lesion on the forearm and
hand: A rare presentation and review of literature.
PMID- 28707651
TI - Chemical environmental factors: Can they affect acne?
PMID- 28707652
TI - Thermal Ablation in the Management of Adrenal Metastasis Originating from Non
small Cell Lung Cancer: A 5-year Single-center Experience.
AB - BACKGROUND: Treatment of adrenal metastasis from lung carcinoma may prolong
survival in the selected patients. However, not all patients can undergo surgery;
thus, minimally invasive ablation procedures such as radiofrequency ablation
(RFA) and microwave ablation (MWA) have gained acceptance as alternative
treatment methods. This study summarized a 5-year single-center experience
regarding the evaluation of safety and efficacy of computed tomography (CT)
guided thermal ablation in the management of adrenal metastasis originating from
non-small cell lung cancer (NSCLC). METHODS: The data of NSCLC patients ablated
for adrenal metastasis at the Department of Diagnostic Imaging and Interventional
Radiology, General Hospital Sotiria, were retrospectively analyzed. Patients were
divided into two groups: RFA group and MWA group according to the therapeutic
approaches. Preprocedural blood tests included measurement of international
normalized ratio, partial thromboplastin time, and platelet enumeration. A dual
phase contrast-enhanced spiral CT was performed immediately after the procedure
to assess the immediate response after ablation and to screen for related
complications. Follow-up was performed with CT or magnetic resonance imaging at
1, 3, 6 months and 1 year after ablation and every 6 months thereafter. RESULTS:
A total of 99 ablation sessions in 71 patients with adrenal metastasis
originating from NSCLC were included in the final analysis. Self-limited,
postablation syndrome occurred in 16/99 (16.1%) of ablation sessions. All
procedures were technically successful. Immediate postablation imaging showed no
contrast enhancement of the ablated tumor in all patients. Follow-up imaging at 3
months revealed local tumor progression in 8 (22.8%) patients of the RFA group
and 7 (19.4%) patients of MWA group, all of them underwent a second session
successfully. The 1-year assessment revealed local recurrence of the ablated
tumor in six patients (17.1%) of RFA group and seven patients (19.4%) of MWA
group. Among these 71 patients, those with tumor size >3.5 cm had a higher local
recurrence rate (65.2%, 15/23) than those with tumors <=3.5 cm (16.7%, 8/48; P =
0.012). There was no significant difference in the median survival time between
RFA (14.0 months) and MWA (14.6 months) groups (P > 0.05). CONCLUSIONS: RFA and
MWA showed comparable efficacy and safety in adrenal metastasis treatment.
PMID- 28707653
TI - Canalization technique to obtain deep tissue biopsy of gastrointestinal
subepithelial tumors as an alternative to conventional known techniques.
AB - Background and Objectives: The most accurate technology to detect and diagnose
subepithelial tumors (SETs) is the endoscopic ultrasonography (EUS) combined with
puncture techniques, such as the endoscopic ultrasonography-guided fine-needle
aspiration (EUS-FNA) or the endoscopic ultrasonography-guided fine-needle biopsy.
Going further in the improvement of the results of tumor samples obtained
endoscopically to diagnose the SETs, the canalization technique guided by
miniprobes (MPs) to obtain biopsies of SET could be an alternative to EUS-FNA.
The objective of this study is to analyze the results of samples obtained by this
procedure. Materials and Methods: A multicenter, retrospective study of a review
of a database of 32 consecutive patients with a SET in the digestive tract, from
2000 to 2015 was conducted. All patients underwent EUS-performed by MP, to define
the size, internal echostructure, and layer of origin of tumor. Once the
echostructure was defined, it proceeded to the canalization technique to arrive
to the tumor tissue. Results: The average diameter of SETs in this series (32
patients) was about 21.6+/-11 mm (range: 5-41 mm). The diagnostic accuracy was
28/32, 87.50% (Confidence interval 95%: 76.04%-98.99%), and there were no major
complications. All procedures were performed on outpatients, none of which
required additional hospitalization. The 50% of patients were operated or
endoscopically resected and in all cases, the previous pathological diagnosis was
confirmed. Conclusions: This is a feasible, safe, and effective procedure that
allows to access to inside of SET to obtain deep biopsies. Tumor samples obtained
by deep biopsy, with prior performing of the canalization technique guided by MP,
were sufficient for histopathological and immunohistochemical diagnosis and
similar to those obtained with other known methods (FNA Trucut, ProCore(r),
etc.). However, more prospective comparative studies with a larger number of
patients and different specialists carrying out the procedure to reach a higher
statistical significance are necessary.
PMID- 28707654
TI - A case of a giant cyst in the left lobe of the liver successfully treated with
endoscopic ultrasound-guided fine needle aspiration (with video).
PMID- 28707655
TI - [The FUS protein: Physiological functions and a role in amyotrophic lateral
sclerosis].
AB - Certain forms of amyotrophic lateral sclerosis (ALS) are associated with an
altered compartmentalization of FUS and its aggregation in the cytoplasm of
motoneurons. FUS is a DNA/RNA-binding protein that is involved in DNA repair and
the regulation of transcription, splicing, RNA transport, and local translation.
Two theories have been proposed to explain the mechanism of the
pathophysiological process in ALS. The theories attribute degeneration of motor
neurons to either loss or gain of FUS function. The review describes the main
physiological functions of FUS and considers evidence for each of the theories of
ALS pathogenesis.
PMID- 28707656
TI - [Regulation of heat shock gene expression in response to stress].
AB - Heat shock (HS) genes, or stress genes, code for a number of proteins that
collectively form the most ancient and universal stress defense system. The
system determines the cell capability of adaptation to various adverse factors
and performs a variety of auxiliary functions in normal physiological conditions.
Common stress factors, such as higher temperatures, hypoxia, heavy metals, and
others, suppress transcription and translation for the majority of genes, while
HS genes are upregulated. Transcription of HS genes is controlled by
transcription factors of the HS factor (HSF) family. Certain HSFs are activated
on exposure to higher temperatures or other adverse factors to ensure stress
induced HS gene expression, while other HSFs are specifically activated at
particular developmental stages. The regulation of the main mammalian stress
inducible factor HSF1 and Drosophila melanogaster HSF includes many components,
such as a variety of early warning signals indicative of abnormal cell activity
(e.g., increases in intracellular ceramide, cytosolic calcium ions, or partly
denatured proteins); protein kinases, which phosphorylate HSFs at various Ser
residues; acetyltransferases; and regulatory proteins, such as SUMO and HSBP1.
Transcription factors other than HSFs are also involved in activating HS gene
transcription; the set includes D. melanogaster GAF, mammalian Sp1 and NF-Y, and
other factors. Transcription of several stress genes coding for molecular
chaperones of the glucose-regulated protein (GRP) family is predominantly
regulated by another stress-detecting system, which is known as the unfolded
protein response (UPR) system and is activated in response to massive protein
misfolding in the endoplasmic reticulum and mitochondrial matrix. A translational
fine tuning of HS protein expression occurs via changing the phosphorylation
status of several proteins involved in translation initiation. In addition,
specific signal sequences in the 5'-UTRs of some HS protein mRNAs ensure their
preferential translation in stress.
PMID- 28707657
TI - [Transmission of pathogenic protein aggregates in Alzheimer's disease].
AB - Deposits of amyloid peptide Abeta and intracellular aggregates of
hyperphosphorylated tau protein in the brain of patients are major
neuropathological features of Alzheimer's disease (AD). For a long time, the
possibility of horizontal transmission of Abeta aggregates from cell to cell and
from person to person remained hypothetical, since there was no experimental
evidence. However, in 1993, the formation of senile plaques was confirmed in the
brains of animals after intracerebral injections of AD patient brain homogenates
or homogenates of the brain of transgenic mice enriched with Abeta aggregates.
Other experiments indicate that amyloid peptide Abeta and intracellular
aggregates of hyperphosphorylated tau protein may be transferred from cell to
cell like prions. In 2015 and 2016, it was reported that AD could be transmitted
to humans during medical procedures, i.e., that this disease might be iatrogenic.
This review discusses the mechanisms by which pathogenic Abeta protein can be
transmitted between cells and analyzes the current evidence concerning the
possibility of horizontal Abeta transmission from person to person.
PMID- 28707658
TI - [Phototrophic microorganisms in the symbiotic communities of Baikal sponges:
Diversity of psbA gene (encoding D1 protein of photosystem II) sequences].
AB - The psbA gene, which encodes a major photosystem II protein (protein II or D1),
is a marker for the presence of phototrophic organisms in water communities. We
have pioneered the use of this marker for studying the diversity of phototrophic
microflora of freshwater invertebrates. The object of the study is the microbial
associations accompanying the endemic Baikal sponge Baikalospongia intermedia and
the surrounding aquatic microbial community. Analysis of the psbA gene sequences
in the examined microbiomes demonstrates the presence of various phototrophic
groups, such as Cyanobacteria, Chlorophyta, Heterokonta, Haptophyta, and
Ochrophyta algae, as well as cyanophages. A total of 35 unique psbA gene
sequences have been distinguished in the microbial communities of the endemic
sponge B. intermedia and 32 unique sequences in the water community surrounding
the sponge. These data demonstrate the involvement of sponge symbiotic
communities in the accumulation of primary production and carbon cycle in the
Lake Baikal ecosystem.
PMID- 28707659
TI - [Drug resistance mutations and susceptibility phenotypes of Neisseria gonorrhoeae
isolates in Russia].
AB - Steady growth in the degree of antimicrobial resistance in Neisseria gonorrhoeae
calls for the control of the spreading of resistance mutations. Here we present
the data describing drug resistance mutations, the results of antimicrobial
susceptibility tests, and molecular genotypes of 128 recent N. gonorrhoeae
isolates collected across 9 regions of the Russian Federation. The mutations in
chromosome genes penA, ponA, rpsJ, gyrA, parC, which determine the susceptibility
of N. gonorrhoeae to penicillins, tetracyclines, and fluoroquinolones were
detected by multiplex amplification followed by hybridization on a hydrogel
microarray. The most frequent mutation was an insertion of an aspartate at
position 345 of penA gene (76.6%), whereas mutations Leu421Pro in ponA gene,
Val57Met in rpsJ gene, Ser91Phe in gyrA gene, Asp95Gly in gyrA gene, and Ser87Arg
in parC gene were detected in 32.8-36.7% of strains. One third of studied N.
gonorrhoeae isolates harbored multiple drug resistance mutations in bacterial
chromosome, resulting in the bimodal distribution of mutation profiles and
related patterns of antimicrobial susceptibility. The spread of multiple
resistance could be explained by the vertical transfer of the mutations resulting
in the clonality of the N. gonorrhoeae population.
PMID- 28707660
TI - [Increase in the concentration of sEH protein in renal medulla of ISIAH rats with
inherited stress-induced arterial hypertension].
AB - The concentration of soluble epoxide hydrolase (sEH) protein was studied in renal
medulla of adult rats from hypertensive ISIAH strain and normotensive WAG strain.
The sEH is a key enzyme in metabolism of epoxyeicosatrienoic acids capable of
activating endothelial NO-synthase and nitrogen oxide formation, and therefore
being vasodilators. An increase in the sEH protein concentration (that we found)
allows one to assume that the oxidative stress is increased in the renal medulla
of hypertensive rats, and the bloodflow is decreased.
PMID- 28707661
TI - [The effects of interleukin-1 beta and gamma-quantum braking radiation on
mesenchymal progenitor cells].
AB - In murine bone-marrow stromal microenvironment cells and in human multipotent
mesenchymal stromal cells (MMSCs), proinflammatory cytokine interleukin-1 beta
(IL-1beta) serves as a growth factor. In murine bone tissue, IL-1beta expression
increases in vivo after irradiation. Here, we have presented our evaluation of
the effects of exogenous IL-1beta on the expression of NF-kB transcription
factors in human MMSCs and stromal layer cells of murine long-term bone marrow
cultures (LTBMCs). The cytokine signaling pathway was also activated in murine
LTBMC by braking electron radiation in doses of 3-12 Gy. The level of expression
of genes that code for IL-1beta, IL-1beta type-I receptor and NF-kB and IKK
protein families have been studied at different time points post exposure. In
both human and murine stromal cells, exogenous IL-1beta led to an increase in the
level of expression of its own gene, while levels of expression of NF-kB and IKK
gene families were not substantially changed. Nevertheless, in human cells, a
significant correlation between levels of expression of IL-1beta and all NF-kB
family genes was detected. It points to a similarity in IL-1beta signal pathways
in mesenchymal and hematopoietic cells, where the posttranslational modifications
of NF-kB transcription factors play a major role. The irradiation of murine LTBMC
resulted in a transient increase in the expression of genes that code NF-kB
transcription factors and IL-1beta. These results indicate an important role of
Rel, Rela, Relb, and Nfkb2 genes in the induction of IL-1beta signal pathway in
murine stromal cells. An increase in IL-1beta expression after the irradiation of
stromal cells may be related to both the induction of inflammation due to massive
cell death and to a profound stimulation of the expression of this
proinflammatory cytokine expression.
PMID- 28707662
TI - [C-terminal lysosome targeting domain of CD63 modifies cellular localization of
rabies virus glycoprotein].
AB - The glycoprotein of rabies virus is the central antigen elicited the immune
response to infection; therefore, the majority of developing anti-rabies vaccines
are based on this protein. In order to increase the efficacy of DNA immunogen
encoding rabies virus glycoprotein, the construction of chimeric protein with the
CD63 domain has been proposed. The CD63 is a transmembrane protein localized on
the cell surface and in lysosomes. The lysosome targeting motif GYEVM is located
at its C-terminus. We used the domain that bears this motif (c-CD63) to generate
chimeric glycoprotein in order to relocalize it into lysosomes. Here, it was
shown that, in cells transfected with plasmid that encodes glycoprotein with c
CD63 motif at the C-terminus, the chimeric protein was predominantly observed in
lysosomes and at the cell membrane where the unmodified glycoprotein is localized
in the endoplasmic reticulum and at the cell surface. We suppose that current
modification of the glycoprotein may improve the immunogenicity of anti-rabies
DNA vaccines due to more efficient antibody production.
PMID- 28707663
TI - [Zinc finger protein 521 suppresses osteogenic differentiation of rat mesenchymal
stem cells by inhibiting the Wnt/beta-catenin signaling pathway].
AB - Zinc finger protein 521 (Zfp521) is involved in a number of cellular processes in
a variety of cells and tissues. In the present study, the effects of Zfp521 on
osteogenic differentiation of rat mesenchymal stem cells (MSCs) were
investigated. The results showed that, in rat MSCs, knocking down cellular Zfp521
by short hairpin RNA (shRNA) decreases cell proliferation while promoting ALP
activity, calcium accumulation, and the expression of mRNA that encodes bone
sialoprotein (BSP), osteocalcin (OCN) and Runx2. Furthermore, in Zfp521-depleted
cells, the up-regulation of phospho-Wnt (p-Wnt) and beta-catenin expression
levels was detected. However, over-expression of Zfp521 played the opposite role
in proliferation and osteogenic differentiation of rat MSCs. To further
demonstrate the functions of the Wnt/beta-catenin signaling in Zfp521 regulated
osteogenic differentiation, the activation of Wnt/beta-catenin was blocked with
IWP-2 inhibitor. The suppression of the Wnt/beta-catenin pathway completely
abrogated the effects of Zfp521 knockdown on osteogenic differentiation of rat
MSCs. Therefore, we conclude that Zfp521 regulates osteogenic differentiation of
rat MSCs through the suppression of the Wnt/beta-catenin signaling pathway.
PMID- 28707664
TI - [A study of recombinant human sestrin 1 and sestrin 2 proteins produced in a
prokaryotic system].
AB - Sestrins are highly conserved stress-inducible proteins capable of suppressing
the production of ROS and signalling through mTORC1. Here we report a study of
human sestrin1 (sesn1) and sestrin2 (sesn2) proteins produced in a pET28^(+)
vector based prokaryotic system. Mass spectrometry analysis, western blot and
surface plasmon resonance (SPR) of affinity purified sesn1 and sesn2 proteins
confirmed their identity; biophysical characteristics were observed using
circular dichroism (CD) showing that sesn1 and sesn2 have a predominant alpha
helical structure. Here we describe a simple, one step purification process to
purify a large amount of sestrin proteins with significant yield. Further study
of recombinant human sestrins may further facilitate the understanding of their
roles in eukaryotic cells.
PMID- 28707665
TI - [Human selenium-containing single-chain variable fragment with glutathione
peroxidase activity protects NIH3T3 fibroblast against oxidative damage].
AB - Ultraviolet B (UVB medium wave, 280-315 nm) induces cellular oxidative damage and
apoptosis by producing reactive oxygen species (ROS). Glutathione peroxidase
functions as an antioxidant by catalyzing the reduction of hydrogen peroxide, the
more important member of reactive oxygen species. A human selenium-containing
single-chain variable fragment (se-scFv-B3) with glutathione peroxidase activity
of 1288 U/MUmol was generated and investigated for its antioxidant effects in UVB
induced oxidative damage model. In particular, cell viability, lipid peroxidation
extent, cell apoptosis, the change of mitochondrial membrane potential, caspase-3
activity and the levels of intracellular reactive oxygen species were assayed.
Human se-scFv-B3 protects NIH3T3 cells against ultraviolet B-induced oxidative
damage and subsequent apoptosis by prevention of lipid peroxidation, inhibition
of the collapse of mitochondrial membrane potential as well as the suppression of
the caspase-3 activity and the level of intracellular ROS. It seems that
antioxidant effects of human se-scFv-B3 are mainly associated with its capability
to scavenge reactive oxygen species, which is similar to that of the natural
glutathione peroxidase.
PMID- 28707666
TI - [Identification of proteins associated with transcription factors HOXA9 and E2A
PBX1 by tandem affinity purification].
AB - Chimeric transcription factor E2A-PBX1 induces the development of acute
lymphoblastic B-cell leukemia in children. Using a transgenic mouse model, we
previously demonstrated that homeobox (HOX) gene HOXA9 genetically interact with
E2A-PBX1 gene in the development of B-cell leukemia in mice. HOXA9 itself is a
potent oncogene resulting in myeloid leukemia when overexpressed, which is
strongly accelerated by its collaborator Meis1. HOX, PBX1 and MEIS1 proteins have
been shown to form hetero dimeric or trimeric complexes in different
combinations. Cooperative interaction between PBX1 and HOX proteins enhances
their DNA binding specificity, essential for HOX dependent developmental
programs. PBX1 is retained in E2A-PBX1, and thus the strong transcriptional
activator properties of E2A-PBX1 may lead to aberrant activation of normally
repressed targets of HOX-PBX complexes. However, although there is evidence that
E2A-PBX1 could bind to HOX and MEIS1 proteins it is still unclear whether such
complexes are actually required for leukemic transformation or whether E2A-PBX1
and HOXA9 are each part of larger protein complexes acting in independent
complementing oncogenic pathways. In this study we aim to search for other HOXA9
and E2A-PBX1 interacting proteins. To identify novel proteins interacting with
human E2A-PBX1 or HOXA9 we used tandem affinity purification (TAP) of protein
complexes from 697 pre-B leukemic and HeLa cell lines transduced to express E2A
PBX1 or HOXA9, respectively, with covalently attached FLAG/HA peptides. The
protein composition of each complex was determined using tandem mass
spectrometry. In the E2A-PBX1 containing complex we identified lymphoid
transcription factor IKAROS, chromatin remodeling factors of SWI/SNF family while
multiple subunits of translation initiation factor eIF3, E3 ubiquitin ligase UBR5
emerged from the HOXA9 complex as potential critical protein partners. This is
the first time the protein partners of either E2A-PBX1 or HOXA9 oncoproteins were
identified using an unbiased biochemical approach. The identification of
translation initiation factors associated with HOXA9 might indicate a novel
function for HOX proteins independent of their transcriptional activity.
PMID- 28707667
TI - [The activity of proapoptotic genes increases after renal ischemia/reperfusion].
AB - According to the World Health Organization, pathologies associated with
ischemia/reperfusion occupy the leading position in the structure of mortality.
The efficiency of localized kidney cancer surgery is limited by the damaging
effects of prolonged warm ischemia and reperfusion. Ischemia/reperfusion damage
to renal tissue may be related to changes in the expression profiles of pro- and
antiapoptotic genes. Here, we have presented the longitudinal expression profiles
of apoptosis-related genes in tissues of left and right (intact) kidneys of male
rats exposed to unilateral ischemia followed by reperfusion. The profiles have
been assessed at time points of 1, 3, and 48 h after the ischemic/reperfusion
exposure by RT-qPCR quantification of mRNAs encoded by 13 genes, including BAX,
p53, AIFM1, APAF1, CASP8, CASP3, CASP9,CASP7, MDM2, BCL2, CIAP1, XIAP, and ICAD,
after normalization with respect to a reference gene ACTB. The study revealed a
shift in the expression of pro- and antiapoptotic genes toward the predominance
of proapoptotic processes, as was evinced by the increase in expression detected
for the BAX, p53, AIFM1, APAF1, and CASP8 genes. One hour after the reperfusion,
activation of mitochondrial, or intrinsic apoptosis was detected, while r53
dependent and extrinsic, i.e., receptor-driven, apoptosis joined at later time
points. Changes in the level of expression of caspase 7 (CASP7)-encoding mRNA
have only been detected 48 h after the restoration of blood flow. Changes have
been observed in the transcription of pro- and antiapoptotic genes in tissues of
both kidneys, which suggests the involvement of the contralateral kidney in
systemic pathological process that develops during unilateral
ischemia/reperfusion.
PMID- 28707668
TI - [Low-molecular-weight regulators of biogenic polyamine metabolism affect cytokine
production and expression of hepatitis S virus proteins in Huh7.5 human
hepatocarcinoma cells].
AB - Hepatitis C virus (HCV) induces the expression of the genes of proinflammatory
cytokines, the excessive production of which may cause cell death, and contribute
to development of liver fibrosis and hepatocarcinoma. The relationship between
cytokine production and metabolic disorders in HCV-infected cells remains
obscure. The levels of biogenic polyamines, spermine, spermidine, and their
precursor putrescine, may be a potential regulator of these processes. The
purpose of the present work was to study the effects of the compounds which
modulate biogenic polyamines metabolism on cytokine production and HCV proteins
expression. Human hepatocarcinoma Huh7.5 cells have been transfected with the
plasmids that encode HCV proteins and further incubated with the following low
molecular compounds that affect different stages of polyamine metabolism: (1)
difluoromethylornithine (DFMO), the inhibitor of ornithine decarboxylase, the
enzyme that catalyzes the biosynthesis of polyamines; (2) N,N'-bis(2,3-butane
dienyl)-1,4-diaminobutane (MDL72.527), the inhibitor of proteins involved in
polyamine degradation; and (3) synthetic polyamine analog N^(I),N^(II)
diethylnorspermine (DENSpm), an inducer of polyamine degradation enzyme. The
intracellular accumulation and secretion of cytokines (IL-6, IL-1beta, TNF-alpha,
and TGF-beta) was assessed by immunocytochemistry and in the immunoenzyme assay,
while the cytokine gene expression was studied using reverse transcription and
PCR. The effects of the compounds under analysis on the expression of HCV
proteins were analyzed using the indirect immunofluorescence with anti-HCV
monoclonal antibodies. It has been demonstrated that, in cells transfected with
HCV genes, DFMO reduces the production of three out of four tested cytokines,
namely, TNF-alpha and TGF-beta in cells that express HCV core, E1E2, NS3, NS5A,
and NS5B proteins, and IL-1beta in the cells that express HCV core, E1E2, and NS3
proteins. MDL72527 and DENSpm decreased cytokine production to a lesser extent.
Incubation with DFMO led to a 28-32% decrease in the number of cells expressing
NS5B or NS5A, both of which are key components of the HCV replication complex.
The results obtained in the work indicate that a further detailed study of the
antiviral activity of DFMO is required in order to assess its potential as an
anti-hepatitis C therapeutic agent.
PMID- 28707669
TI - [Planar molecular arrangements aid the design of MHC class II binding peptides].
AB - The coupling between peptides and MHC-II proteins in the human immune system is
not well understood. This work presents an evidence-based hypothesis of a guiding
intermolecular force present in every human MHC-II protein (HLA-II). Previously,
we examined the spatial positions of the fully conserved residues in all HLA-II
protein types. In each one, constant planar patterns were revealed. These
molecular planes comprise of amino acid groups of the same chemical species (for
example, Gly) distributed across the protein structure. Each amino acid plane has
a unique direction and this directional element offers spatial selectivity.
Constant within all planes, too, is the presence of an aromatic residue
possessing electrons in movement, leading the authors to consider that the planes
generate electromagnetic fields that could serve as an attractive force in a
single direction. Selection and attraction between HLA-II molecules and antigen
peptides would, therefore, be non-random, resulting in a coupling mechanism as
effective and rapid as is clearly required in the immune response. On the basis
of planar projections onto the HLA-II groove, modifications were made by
substituting the key residues in the class II-associated invariant chain peptide
a peptide with a universal binding affinity-resulting in eight different modified
peptides with affinities greater than that of the unmodified peptide. Accurate
and reliable prediction of MHC class II-binding peptides may facilitate the
design of universal vaccine-peptides with greatly enhanced binding affinities.
The proposed mechanisms of selection, attraction and coupling between HLA-II and
antigen peptides are explained further in the paper.
PMID- 28707670
TI - [Enzymatic synthesis of high-modified DNA].
AB - Here, we describe the synthesis and purification of six deoxyuridine triphosphate
derivatives that contain protein-like functional groups and alkene linkers of
various lengths. Using KOD XL and Deep Vent polymerases, these derivatives have
been incorporated into single-stranded DNA, achieving a high degree of DNA
modification. These polymerases are able to utilize highly modified DNA strands
as templates for synthesizing unmodified DNA. The synthesized deoxyuridine
triphosphate derivatives are promising as substrates for producing modified
aptamers to various target proteins using, e.g., the systematic evolution of
ligands by exponential enrichment (SELEX) methodology.
PMID- 28707671
TI - Cardiomyocyte proliferation: remove brakes and push accelerators.
AB - Adult mammalian hearts cannot repair by themselves after injury due to limited
proliferation of cardiomyocytes; removal of cell cycle blocker and/or addition of
drugs that boost proliferation of cardiomyocytes provide potential means to
cardiac regeneration. Three publications that appeared recently in Nature and
Cell Research now provide new hope to the treatment of heart injuries.
PMID- 28707672
TI - Hydroxychloroquine and the eye: an old unsolved problem.
PMID- 28707673
TI - Increased corneal densitometry as a subclinical corneal change associated with
multiple myeloma.
PMID- 28707674
TI - Are techniques for general anesthesia less invasive than procedures for cataract
surgery?
PMID- 28707675
TI - Submacular hemorrhage and grape-like polyp clusters: factors associated with
reactivation of the lesion in polypoidal choroidal vasculopathy.
AB - PurposeThe purpose of this study is to investigate the factors associated with
reactivation of the lesion during the first year in patients with polypoidal
choroidal vasculopathy (PCV) treated with intravitreal ranibizumab.Patients and
methodsThis retrospective observational study included 84 eyes diagnosed with PCV
and treated with 3-monthly ranibizumab injections. Only those patients who
exhibited complete resolution of fluid after initial treatment and were followed
up at least 12 months were included. The baseline characteristics of the
patients, including their age and sex, location of the polyps, greatest linear
dimensions of the lesions, largest polyp diameter, choroidal vascular
hyperpermeability, submacular hemorrhages >=1 disc area in size, presence of
grape-like polyp clusters, central foveal thickness, and best-corrected visual
acuity were compared between patients with and without reactivation of the
lesion.ResultsDuring the 12-month follow-up period, reactivation of the lesion
was observed in 60 patients (71.4%). The first reactivation was noted at a mean
duration of 3.9+/-1.7 months after the third ranibizumab injection. Cox
regression analysis revealed that the absence of submacular hemorrhages >=1 disc
area (P=0.009), presence of grape-like polyp clusters (P=0.002), and greatest
linear dimension of the lesions (P=0.019) were associated with reactivation of
the lesion.ConclusionThe absence of submacular hemorrhages, presence of grape
like polyp clusters, and large lesion size at diagnosis were associated with a
high risk of reactivation of PCV in patients treated with intravitreal
ranibizumab. Patients exhibiting these characteristics may require close
monitoring.
PMID- 28707676
TI - Obesity: Olfactory senses linked to metabolism.
PMID- 28707677
TI - 'Omics' and endocrine-disrupting chemicals - new paths forward.
AB - The emerging field of omics - large-scale data-rich biological measurements of
the genome - provides new opportunities to advance and strengthen research into
endocrine-disrupting chemicals (EDCs). Although some EDCs have been associated
with adverse health effects in humans, our understanding of their impact remains
incomplete. Progress in the field has been primarily limited by our inability to
adequately estimate and characterize exposure and identify sensitive and
measurable outcomes during windows of vulnerability. Evolving omics technologies
in genomics, epigenomics and mitochondriomics have the potential to generate data
that enhance exposure assessment to include the exposome - the totality of the
lifetime exposure burden - and provide biology-based estimates of individual
risks. Applying omics technologies to expand our knowledge of individual risk and
susceptibility will augment biological data in the prediction of variability and
response to disease, thereby further advancing EDC research. Together, refined
exposure characterization and enhanced disease-risk prediction will help to
bridge crucial gaps in EDC research and create opportunities to move the field
towards a new vision - precision public health.
PMID- 28707678
TI - Cardiovascular endocrinology: Is ANGPTL3 the next PCSK9?
PMID- 28707680
TI - Targeted therapies: Lenvatinib SELECTs survival benefit.
PMID- 28707681
TI - Liver: Paradigm shift in the immunopathogenesis of NAFLD.
PMID- 28707679
TI - Anaplastic thyroid carcinoma: from clinicopathology to genetics and advanced
therapies.
AB - Anaplastic thyroid carcinoma (ATC) is a rare malignancy, accounting for 1-2% of
all thyroid cancers. Although rare, ATC accounts for the majority of deaths from
thyroid carcinoma. ATC often originates in a pre-existing thyroid cancer lesion,
as suggested by the simultaneous presence of areas of differentiated or poorly
differentiated thyroid carcinoma. ATC is characterized by the accumulation of
several oncogenic alterations, and studies have shown that an increased number of
oncogenic alterations equates to an increased level of dedifferentiation and
aggressiveness. The clinical management of ATC requires a multidisciplinary
approach; according to recent American Thyroid Association guidelines, surgery,
radiotherapy and/or chemotherapy should be considered. In addition to
conventional therapies, novel molecular targeted therapies are the most promising
emerging treatment modalities. These drugs are often multiple receptor tyrosine
kinase inhibitors, several of which have been tested in clinical trials with
encouraging results so far. Accordingly, clinical trials are ongoing to evaluate
the safety, efficacy and effectiveness of these new agents. This Review describes
the updated clinical and pathological features of ATC and provides insight into
the molecular biology of this disease. The most recent literature regarding
conventional, newly available and future therapies for ATC is also discussed.
PMID- 28707682
TI - Retraction Note: Thyroid nodules update in diagnosis and management.
AB - [This retracts the article DOI: 10.1186/s40842-015-0011-7.].
PMID- 28707683
TI - Retraction Note: Fatal factitious Cushing syndrome (Munchhausen's syndrome) in a
patient with macroprolactinoma and silent corticotrophinoma: case report and
literature review.
AB - [This retracts the article DOI: 10.1186/s40842-015-0002-8.].
PMID- 28707684
TI - Conformer specific nonadiabatic reaction dynamics in the photodissociation of
partially deuterated thioanisoles (C6H5S-CH2D and C6H5S-CHD2).
AB - In this work, we have investigated nonadiabatic dynamics in the vicinity of
conical intersections for predissociation reactions of partially deuterated
thioanisole molecules: C6H5S-CH2D and C6H5S-CHD2. Each isotopomer has two
distinct rotational conformers according to the geometrical position of D or H of
the methyl moiety with respect to the molecular plane for C6H5S-CH2D or C6H5S
CHD2, respectively, as spectroscopically characterized in our earlier report [J.
Lee, S.-Y. Kim and S. K. Kim, J. Phys. Chem. A, 2014, 118, 1850]. Since
identification and separation of two different rotational conformers of each
isotopomer have been unambiguously done, we could interrogate nonadiabatic
dynamics of thioanisole in terms of both H/D substitutional and conformational
structural effects. Nonadiabatic transition probability, estimated by the
experimentally measured branching ratio of the nonadiabatically produced ground
state channel giving C6H5S.(X[combining tilde]) versus the adiabatic excited
state channel leading to the C6H5S.(A) radical, shows resonance-like increases at
symmetric (nus) or asymmetric (7a) S-CH2D (or S-CHD2) stretching mode excitation
in S1 for all conformational isomers of two isotopomers. However, absolute
probabilistic value of the nonadiabatic transition is found to vary quite
drastically depending on different conformers and isotopomers. The experimental
finding that nonadiabatic transition dynamics are very sensitive to subtle
changes in the nuclear configuration within the Franck-Condon region induced by
the H/D substitution indicates that the S1/S2 conical intersection seam is quite
narrowly defined in the multi-dimensional nuclear configurational space as far as
the S-methyl predissociation reaction is concerned. In order to understand the
relation between molecular structure and nonadiabaticity of reaction, potential
energy surfaces near S1/S2 conical intersections have been theoretically
calculated along nus and 7a normal mode coordinates for all conformational
isomers. Slow-electron velocity map imaging (SEVI) spectroscopy is employed to
unravel the extent of intramolecular vibrational redistribution (IVR) for
particular mode excitations of S1, providing insights into the dynamic interplay
between IVR and nonadiabatic transition probability near the conical intersection
seam.
PMID- 28707685
TI - Structural assignment of small cationic silver clusters by far-infrared
spectroscopy and DFT calculations.
AB - The structures of small cationic silver clusters Agn+ (n = 3-13) are investigated
by comparing measured far-infrared multiple photon dissociation spectra of
cluster-argon complexes with the calculated harmonic vibrational spectra of
different low-energy structural isomers. A global structure search was carried
out using the CALYPSO structure prediction method, after which isomers were
locally optimized with the meta GGA functional TPSS. The obtained structures of
the cationic silver clusters are mostly consistent with earlier ion mobility
measurements and photodissociation spectroscopy studies for Agn+ (n = 3-11) and
allowed excluding several structural isomers that were considered in those
earlier studies, which illustrates the strength of combining multiple
experimental techniques for conclusive structural identification. The growth
pattern of the cationic silver clusters is discussed and differences with other
cationic coinage metal clusters are highlighted.
PMID- 28707686
TI - Increasing p-type dye sensitised solar cell photovoltages using polyoxometalates.
AB - Lindqvist polyoxometalate (POM) additives increase VOC in p-type DSSCs by up to
140%, yielding substantial efficiency gains for poorly matched dyes and redox
mediators. For better dye/electrolyte combinations, these gains are typically
outweighed by losses in JSC. Charge lifetime and transient IR measurements show
that this is due to retardation of both recombination and electron transfer to
the mediator, and a positive shift in the NiO valence band edge. The POMs also
show their own, limited sensitizing effect.
PMID- 28707687
TI - Polytypism in the ground state structure of the Lennard-Jonesium.
AB - We present a systematic study of the stability of nineteen different periodic
structures using the finite range Lennard-Jones potential model discussing the
effects of pressure, potential truncation, cutoff distance and Lennard-Jones
exponents. The structures considered are the hexagonal close packed (hcp), face
centred cubic (fcc) and seventeen other polytype stacking sequences, such as dhcp
and 9R. We found that at certain pressure and cutoff distance values, neither fcc
nor hcp is the ground state structure as previously documented, but different
polytypic sequences. This behaviour shows a strong dependence on the way the tail
of the potential is truncated.
PMID- 28707688
TI - Probing the excited-state chemical shifts and exchange parameters by nitrogen
decoupled amide proton chemical exchange saturation transfer (HNdec-CEST).
AB - CEST-NMR spectroscopy is a powerful tool for probing the conformational dynamics
of macromolecules. We present a HNdec-CEST experiment that simplifies the
relaxation matrix, reduces fitting parameters, and enhances signal resolution.
Importantly, fitting of HNdec-CEST profiles enables robust extraction of exchange
rates as well as excited-state chemical shifts and populations.
PMID- 28707689
TI - Correction: Privileged chiral N-heterocyclic carbene ligands for asymmetric
transition-metal catalysis.
AB - Correction for 'Privileged chiral N-heterocyclic carbene ligands for asymmetric
transition-metal catalysis' by Daniel Janssen-Muller et al., Chem. Soc. Rev.,
2017, DOI: .
PMID- 28707690
TI - A non-enzyme cascade amplification strategy for colorimetric assay of disease
biomarkers.
AB - A non-enzyme cascade amplification strategy, based on the dissolution of Ag
nanoparticles and a Pt nanocube-catalyzed reaction, for colorimetric assay of
disease biomarkers was developed. This strategy overcomes the intrinsic
limitations of enzymes involved in conventional enzymatic amplification
techniques, thanks to the utilization of noble-metal nanostructures with superior
properties.
PMID- 28707691
TI - With unprotected amino acids to tetrazolo peptidomimetics.
AB - Here we describe the direct usage of C,N-unprotected amino acids in Ugi-tetrazole
reactions to produce a novel class of acid-tetrazole compounds. Surprisingly,
only the tetrazole Ugi product is found and not traces of other possible Ugi type
reactions. Based on this reaction pathway we have designed the synthesis of novel
tetrazole-peptidomimetics. A high level of structural diversity can be achieved
using this isocyanide based multicomponent reaction (IMCR), providing a platform
for the production of functionalized building blocks for novel bioactive
molecules and nontraditional scaffolds which previously were not accessible.
PMID- 28707692
TI - Sequential dynamic structuralisation by in situ production of supramolecular
building blocks.
AB - We herein report an example of sequential dynamic higher structuralisation from
disordered droplets into higher-ordered structures, resulting in the formation of
a hydrogel. This is a potential model for understanding complicated biosystems in
which lower-ordered structures evolve into higher-ordered structures that
interact with specific molecules.
PMID- 28707693
TI - Single-step fabrication of multi-compartmentalized biphasic proteinosomes.
AB - Multi-compartmentalized biphasic proteinosomes were self-assembled using a single
step double Pickering emulsion procedure, and exploited for enzyme-mediated
interfacial catalysis, polysaccharide shell templating, and hydrogel
functionalization.